DEJA REVIEW™

USMLE Step 1

NOTICE

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DEJA REVIEW™

USMLE Step 1

Second Edition

John H. Naheedy, MD

Fellow, Pediatric Radiology

Department of Radiology

Children’s Hospital Boston

Harvard Medical School

Boston, Massachusetts

Daniel A. Orringer, MD

Chief Resident

Department of Neurosurgery

University of Michigan Medical School

Ann Arbor, Michigan

Copyright © 2010, 2006 by John H. Naheedy and Daniel A. Orringer. All rights reserved. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher.

ISBN: 978-0-07-163786-2

MHID: 0-07-163786-9

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THE WORK IS PROVIDED “AS IS.” McGRAW-HILL AND ITS LICENSORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. McGraw-Hill and its licensors do not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free. Neither McGraw-Hill nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting there from. McGraw-Hill has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise.

To my family and friends, for their love and encouragement; and to my parents, for being an example of everything I want to be.

—John

To my mother and my family.

—Dan

Contents

Contributors

Student Reviewers

Preface

Acknowledgments

Chapter 1 BASIC PRINCIPLES

Molecular Biology, Biochemistry, and Genetics

Nutrition

General Embryology

Basic Pathology

Basic Pharmacology

Chapter 2 IMMUNOLOGY

Immunology Basics

Pathology Immune System

Chapter 3 MICROBIOLOGY AND INFECTIOUS DISEASES

Bacteriology

Antibiotics

Virology

Antiviral Agents

Mycology

Antifungals

Parasitology

Chapter 4 NEUROSCIENCE

Embryology

Neuroanatomy and Neurophysiology

Pathology of the Nervous System

Pharmacology of the Nervous System

Chapter 5 CARDIOVASCULAR

Embryology

Anatomy

Physiology

Cardiovascular Pathology and Pathophysiology

Pharmacology

Chapter 6 PULMONARY

Embryology

Anatomy

Physiology

Pathology

Other Pathology

Pharmacology

Chapter 7 GASTROENTEROLOGY

Embryology

Anatomy

Physiology

Pathology

Pharmacology

Chapter 8 REPRODUCTION AND ENDOCRINOLOGY

Embryology

Anatomy

Physiology

Pathology

Pharmacology

Chapter 9 RENAL AND GENITOURINARY

Embryology

Anatomy

Physiology

Functional Regions of the Nephron

Endocrine Functions of the Kidney

Pathology

Pharmacology—Renal

Chapter 10 HEMATOLOGY AND ONCOLOGY

Embryology

Pathology

Pharmacology

Chapter 11 SKIN AND CONNECTIVE TISSUES

Embryology/Anatomy/Histology

Pathology

Chapter 12 MUSCULOSKELETAL

Anatomy

Physiology

Musculoskeletal and Connective Tissue Pathology

Chapter 13 BEHAVIORAL SCIENCES

Life Cycle

Physiology

Substance Abuse

Psychology

Psychiatry

Pharmacology—Psychopharmacology

Medical Ethics

Biostatistics

Public Health/Epidemiology

Chapter 14 MAKE THE DIAGNOSIS

Nutrition

Microbiology and Infectious Diseases

Neuroscience

Cardiovascular

Pulmonary

Gastroenterology

Reproductive/Endocrine

Renal and Genitourinary

Hematology/Oncology

Skin and Connective Tissues

Musculoskeletal

Behavioral Science

Appendix ABBREVIATIONS

Index

Contributors

Alexander Choo

Medical Student

Class of 2010

University of California, San Diego

La Jolla, California

Chapters: Pulmonary, Skin and Connective Tissues, Musculoskeletal

Charlotte Gore

Medical Student

Class of 2010

University of California, San Diego

La Jolla, California

Chapters: Basic Principles, Neuroscience, Gastroenterology, Hematology and Oncology, Behavioral Science, Make the Diagnosis

Kristen A. Kipps

Medical Student

Class of 2010

University of California, San Diego

La Jolla, California

Chapters: Immunology, Microbiology and Infectious Diseases

Brian S. Pugmire

Medical Student

Class of 2010

University of California, San Diego

La Jolla, California

Chapter: Renal and Genitourinary

Krishna C. Ravi

Medical Student

Class of 2010

University of California, San Diego

La Jolla, California

Chapter: Cardiovascular

Omeed Saghafi

Medical Student

Class of 2010

University of California, San Diego

La Jolla, California

Chapter: Reproduction and Endocrinology

Student Reviewers

Betty Chung

MD/PhD Candidate

University of Medicine and Dentistry of New Jersey

School of Osteopathic Medicine

Class of 2012

Sarah Fabiano

SUNY Upstate Medical University

Class of 2010

Ali Rizvi, MPH

Lake Erie College of Osteopathic Medicine

Class of 2010

Preface

Déjà Review™ USMLE Step 1 has been scrutinized and edited to produce a second edition that is even higher yield and easier to use than the first. Outstanding medical students who have recently taken Step 1 have revised the original text to ensure the material covered herein is complete and current. The authors, now with a combined 30 years of experience in the medical field, have also edited the manuscript to emphasize the relevant core concepts covered in the USMLE Step 1 examination. We are confident that our efforts have produced one of the most useful guides for Step 1 review available today.

The main objective of a medical student preparing for Step 1 of the United States Medical Licensing Examination (USMLE) is to commit a vast body of knowledge to memory. Having recently prepared for Step 1, we realize how daunting this task can be. We feel there are two main principles that will allow you to be successful in your preparations for Step 1: (1) repetition of key facts and (2) using review questions to gauge your comprehension and memory. The Déjà Review™ series is a unique resource that has been designed to allow you to review the essential facts and determine your level of knowledge on the subjects tested on Step 1. We also know, from experience, that building a solid foundation in the basic sciences will allow you to make a smooth transition into the clinical years of medical school.

ORGANIZATION

All concepts are presented in a question and answer format that covers the key facts on hundreds of commonly tested USMLE Step 1 topics. The material is divided into chapters organized by body systems. Special emphasis has been placed on the molecular and genetic basis of pathology, as this area has become increasingly emphasized in recent examinations.

This question and answer format has several important advantages:

- It provides a rapid, straightforward way for you to assess your strengths and weaknesses.

- It allows you to efficiently review and commit to memory a large body of information.

- It offers a break from tedious, convoluted multiple-choice questions.

- The “Make the Diagnosis” section exposes you to the prototypic presentation of diseases classically tested on the USMLE Step 1.

- It serves as a quick, last-minute review of high-yield facts.

The compact, condensed design of the book is conducive to studying on the go, especially during any downtime throughout your day.

HOW TO USE THIS BOOK

This text has been sampled by a number of medical students who found it to be an essential part of their preparation for Step 1, in addition to their course examinations. Remember, this text is not intended to replace comprehensive textbooks, course packs, or lectures. It is simply intended to serve as a supplement to your studies during your first 2 years of medical school and throughout your preparation for Step 1. We encourage you to begin using this book early in your first year to reinforce topics covered in your course examinations. We also recommend having the book spiral bound to make it more portable and easier to use outside of the library or classroom. You may cover up the answers with the included bookmark and quiz yourself or even your classmates. For a greater challenge, try covering up the questions!

However you choose to study, we hope you find this resource helpful throughout your preclinical years and during your preparation for the USMLE Step 1. Best of luck!

John H. Naheedy, MD

Daniel A. Orringer, MD

Acknowledgments

The authors would like to thank the following individuals for their invaluable contributions to this text and their efforts in making this a useful, accurate resource for students:

Stephen M. Baird, MD

Professor Emeritus of Pathology

School of Medicine

University of California, San Diego

Veterans Affairs San Diego Healthcare System

La Jolla, California

Vi Q. Bowman, MD

Fellow, Department of Internal Medicine

Division of Infectious Diseases

University of California San Diego, Medical Center

San Diego, California

David L. Clark, PhD

Associate Professor

Division of Anatomy

College of Medicine

Ohio State University

Columbus, Ohio

John J. Curry III, PhD

Director, Problem-Based Learning Pathway

Associate Professor, Departments of Physiology & Obstetrics and Gynecology

College of Medicine

Ohio State University

Columbus, Ohio

Robert M. DePhilip, PhD

Associate Professor

Division of Anatomy

College of Medicine

Ohio State University

Columbus, Ohio

Richard Fertel, PhD

Associate Professor

Department of Pharmacology

College of Medicine

Ohio State University

Columbus, Ohio

Heather L. Hofflich, DO

Deparment of Internal Medicine

Division of Endocrinology, Diabetes and Metabolism

University of California, San Diego

La Jolla, California

John H. Hughes, PhD

Associate Professor

Department of Molecular Virology, Immunology, and Medical Genetics

College of Medicine

Ohio State University

Columbus, Ohio

Carolyn J. Kelly, MD

Professor

Dept. of Internal Medicine

Associate Dean for Admissions and Student Affairs

University of California, San Diego

La Jolla, California

David E. Krummen, MD

Assistant Professor of Medicine

Division of Electrophysiology

University of California San Diego

Veterans Affairs San Diego Healthcare System

La Jolla, California

Nora D. Laiken, PhD

Assistant Dean of Educational Support Services

School of Medicine

University of California, San Diego

La Jolla, California

Jess Mandel, MD

Professor

Department of Internal Medcine

Division of Pulmonary & Critical Care

Associate Dean for Undergraduate Medical Education

University of California, San Diego

La Jolla, California

Khashayar Mohebali, MD

Chief Resident, Clinical Instructor

Division of Plastic and Reconstructive Surgery

Department of Surgery

Department of Surgery

University of California, San Francisco

San Francisco, California

Alexandra Schwartz, MD

Associate Clinical Professor

Department of Orthopedic Surgery

University of California, San Diego Medical Center

San Diego, California

Pal L. Vaghy, MD

Associate Professor

Department of Molecular and Cellular Biochemistry

College of Medicine

Ohio State University

Columbus, Ohio

The authors would like to recognize the faculty and staff at the Ohio State University College of Medicine and dedicate this edition to the memory of the late Dr. John M. Stang, for his constant encouragement and his endless commitment to education. We would also like to thank the students who used this text in preparation for their boards and provided critical feedback. Finally, a special thanks to Lilly Ghahremani of Full Circle Literary for her guidance, and to our managing editor Kirsten Funk for her patience and guidance throughout this project.

CHAPTER 1

Basic Principles

MOLECULAR BIOLOGY, BIOCHEMISTRY, AND GENETICS

DNA, Genes, and Chromosomes

Which nucleotide bases are purines and which are pyrimidines?

“CUT the PY”: Cytosine, Uracil, and Thymine = PYrimidines; “PURe As Gold”: PURines = adenine and guanine

Which proteins make up the core of a nucleosome?

Histones: H2A, H2B, H3, and H4

Which proteins are associated with DNA between nucleosomes?

Histone H1

Name the type of mutations described below:

Type of mutation that does not result in a change in amino acid sequence

Silent

Type of mutation that results in a change in amino acid sequence

Missense

Type of mutation that results in a stop codon

Nonsense “NO sense”

Type of mutation that changes the reading frame

Frameshift

Type of mutation in which a portion of DNA is lost

Deletion

Type of mutation in which a single base is exchanged

Point

Name the type of cytogenetic disorders described below:

Failure of chromosomes to disjoin properly during cell division

Nondisjunction

Loss of a portion of a chromosome

Deletion

Two internal chromosomal breaks with inverted reincorporation of a portion of the chromosome

Inversion

Single breaks in two chromosomes resulting in the exchange of segments between chromosomes without loss of genetic material

Balanced reciprocal translocation

Single breaks in two acrocentric chromosomes resulting in one large chromosome and one small chromosome accompanied by the loss of some genetic information, hereditary form of Down syndrome

Robertsonian translocation

Mitotic error in early development leading to the development of two karyotypically distinct populations of cells in an organism

Mosaisicm

What term is used to describe the AT-rich sequences in the genome where DNA replication begins?

Origin of replication

DNA Replication, Transcription, and Translation

Name the protein(s) involved in replication or DNA repair with the functions listed below:

Stabilize single-stranded DNA

Single-stranded DNA-binding proteins

Recognition of AT-rich sequences at the origin of replication and separation of DNA strands in bacteria (prokaryotes)

DnaA protein

Unwinding DNA double helix

DNA helicases

Prevention of supercoiling during replication

DNA topoisomerases

Placement of RNA primer at site where replication is initiated

Primase, and an RNA polymerase

Removal of RNA primers from DNA synthesized discontinuously

DNA polymerase I (specifically, the 5’-3’ exonuclease activity)

DNA chain elongation in prokaryotes

DNA polymerase III

Proofreading of newly synthesized DNA strand

DNA polymerase III (specifically, the 3’-5’ exonuclease activity)

Repair UV damage to DNA

UV-specific endonuclease, exonuclease, and DNA ligase

Removal of damaged bases from DNA

Apurinic or apyrimidinic endonuclease, exonuclease, and DNA ligase

What term is used to describe the DNA strand synthesized continuously toward the replication fork?

Leading strand

What term is used to describe the DNA strand synthesized discontinuously away from the replication fork?

Lagging strand

What are the three stop codons?

UGA, UAA, UAG (U Go Away, U Are Away, U Are Gone)

In which direction are DNA and RNA synthesized?

5’ → 3’

What is the start codon?

AUG

Name the type of RNA responsible for each of the following functions:

Largest RNA molecule

mRNA

Most abundant type of RNA

rRNA

Smallest RNA molecule

tRNA

Portion of RNA transcript encoding information for protein synthesis

Exons (“exons are expressed”)

Portion of RNA transcript that is found between sequences of RNA encoding information for protein synthesis

Introns

Type of RNA covalently bound to a single amino acid

tRNA

Name the term used to describe the region of genomic DNA where RNA polymerase and transcription factors bind to regulate transcription:

Promoter

Name the term used to describe the region of genomic DNA where transcription factors activators bind to enhance transcription:

Enhancer

Name the term to describe the region of genomic DNA where repressors bind.

Silencer

Name the enzyme responsible for each of the following functions:

Synthesis of rRNA

RNA polymerase I

Synthesis of mRNA

RNA polymerase II

Synthesis of tRNA

RNA polymerase III

Name three major regulatory mechanisms of transcription in eukaryotes:

1. Regulation by transcription factors at the level of the promoter

2. Regulation by histones binding to specific genomic regions

3. Regulation of DNA structure (including methylation, gene rearrangement, and amplification)

What genetic structure regulates transcription in prokaryotes?

An operon

Name the elements of an operon responsible for each of the following functions:

Region where proteins bind to enable transcription

Promoter region

Molecule that binds at the promoter

Activator or repressor

Sequence in DNA where regulatory protein bind

Operator

Molecule that binds the operator to regulate transcription

Repressor

What are three modifications made to an RNA transcript before it leaves the nucleus?

1. 5’ Capping with 7-methylguanosine

2. 3’ Polyadenylation

3. Splicing of introns

Which small molecule provides the energy for charging a tRNA with its amino acid?

Adenosine triphosphate (ATP)

Which small molecule provides the energy for binding tRNA to the ribosome and for translocation?

Guanosine triphosphate (GTP)

Which molecules, central to the discipline of molecular biology, recognize and cleave specific sequences of a DNA molecule?

Restriction enzymes

Molecular Biology Techniques

Name the molecular biology techniques described below:

Method of separating molecules based on movement through a gel placed in an electric field

Gel electrophoresis

Technique for detecting specific DNA sequences using restriction enzymes and a radiolabeled DNA probe

Southern blot

Technique for detecting specific RNA sequences using restriction enzymes and a radiolabeled DNA probe

Northern blot

Technique for detecting specific protein sequences using radiolabeled antibodies

Western blot

A rapid technique for amplifying a specific DNA sequence in vitro

Polymerase chain reaction

Technique for detecting different alleles at a gene of interest using restriction enzymes

Restriction fragment length polymorphism analysis

Technique for detecting the presence of antigen or antibody using radiolabeled antibodies

Radioimmunoassay (RIA)

Technique for detecting the presence of antigen or antibody using antibodies linked to enzymes with detectable activity

Enzyme-linked immunosorbent assay (ELISA)

Inherited Diseases

Name inheritance patterns described below:

Twenty-five percent of offspring from two carrier parents affected

Autosomal recessive (AR)

Commonly cause defects in structural genes

Autosomal dominant (AD)

Commonly cause defects in enzymes

AR

Defect seen in multiple generations in both sexes

AD

Defects not typically seen in consecutive generations

AR

Disease is not observed in females.

X-linked (XL) recessive

Disease is transmitted by mother.

Mitochondrial inheritance

Half of male offspring from affected mother will manifest disease.

XL recessive

Disease manifestations commonly present after puberty.

AD

What are the conditions for a population to be in Hardy-Weinberg equilibrium?

1. No mutation at locus of interest

2. No selection for allele at locus of interest

3. Random mating

4. Closed population (no migration)

What are the two Hardy-Weinberg equations?

1. p^2 + 2pq + q^2 = 1

2. p + q = 1 (p and q are separate alleles and pq is the heterozygote frequency)

Name the disease or condition associated with each of the following statements:

Lack of UV-specific endonuclease causing dry skin and malignant melanoma

Xeroderma pigmentosa

Lack of aldolase B causing hypoglycemia, jaundice, and cirrhosis

Fructose intolerance

Lack of fructokinase causing fructosemia and fructosuria

Essential fructosuria

Lack of galactose-1-phosphate uridyltransferase causing cataracts, hepatosplenomegaly (HSM), and mental retardation

Galactosemia

Deficiency of lactase causing bloating, flatulence, and diarrhea on consumption of dairy products

Lactose intolerance

Lactic acidosis and neurologic deficits in an alcoholic

Pyruvate dehydrogenase deficiency

Hemolytic anemia in patients of Mediterranean descent after eating fava beans or taking antimalarial medication

Glucose-6-phosphate dehydrogenase deficiency

Hemolytic anemia due to deficiency in glycolysis

Hexokinase, glucose-phosphate isomerase, aldolase, triose-phosphate isomerase, phosphate glycerate kinase, enolase, or pyruvate kinase deficiency

Inappropriate hepatocellular accumulation of glycogen caused by a deficiency of glucose-6-phosphatase, associated with severe fasting, hypoglycemia, lactic acidosis, hyperlipidemia, and impaired fructose metabolism

von Gierke disease/type I glycogen storage disease

Inappropriate accumulation of glycogen in the liver, heart, and muscle caused by a deficiency of lysosomal α-1,4-glucosidase, resulting in cardiomegaly

Pompe disease/type II glycogen storage disease

Inappropriate accumulation of glycogen in liver and heart due to deficiency of α-1,6-glucosidase, a debranching enzyme often leading to muscular hypotonia

Cori disease/type III glycogen storage disease

Inappropriate accumulation of glycogen in skeletal muscle fibers due to deficiency of glycogen phosphorylase, leading to myalgia and myoglobinuria with exercise

McArdle disease/type V glycogen storage disease

Defect in cystathione synthase leading to the presence of homocysteine in the urine

Homocystinuria

Defect of renal tubular amino acid transporter for cysteine, ornithine, lysine, and arginine

Cystinuria

Inadequate catabolism of branched-chain amino acids (Ile, Val, and Leu) due to lack of α-ketoacid dehydrogenase leading to mental retardation

Maple syrup urine disease

Lack of phenylalanine hydroxylase (PAH) leading to a buildup of phenylalanine resulting in mental retardation, hypopigmentation, eczema, and a mousy odor

Phenylketonuria (can also get Phe buildup due to deficiency of tetrahydrobiopterin, BH4, cofactor of PAH)

Lack of homogentisic acid oxidase leading to a buildup of homogentisate, causing darkening of the urine and connective tissues

Alkaptonuria

Lack of tyrosinase leading to a lack of melanin

Albinism

Lack of adenosine deaminase inhibits DNA synthesis by causing the accumulation of metabolites in the purine salvage pathway; one of the causes of severe combined immunodeficiency syndrome

Adenosine deaminase deficiency

Lack of hypoxanthine-guanine phosphoryltransferase (HGPRTase) causing an overproduction of uric acid leading to neurologic deficits, hyperuricemia, and behavioral abnormalities, including self-mutilation

Lesch-N yhan S yndrome (L acks N ucleotide S alvage)

Trisomy 21 → mental retardation, slanted palpebral fissures, hypertelorism, macroglossia, atrial septal defect (ASD), duodenal atresia, early-onset Alzheimer disease, and multiple visceral anomalies

Down syndrome

Expansion of unstable region of X chromosome (abnormal FMR1 gene with CGG expansion) leading to mental retardation, enlarged testes, and craniofacial anomalies

Fragile X syndrome

XL recessive deficiency of α-galactosidase A → buildup of ceramide trihexoside which causes pain in the extremities, ocular abnormalities, angiokeratomas, cardiovascular disease, and renal failure

Fabry disease

AR deficiency of galactosylceramide β-galactosidase leading to cerebral accumulation of galactocerebroside, which causes progressive neurologic degeneration

Krabbe disease (aka globoid cell leukodystrophy)

AR deficiency of β-glucocerebrosidase leading to the accumulation of glucocerebroside in the brain, bone marrow, liver, spleen →HSM, aseptic necrosis of femur, and neurologic dysfunction

Gaucher disease

AR deficiency of sphingomyelinase on Chromosome 11 leading to buildup of sphinogmyelin and cholesterol in histiocytes of the liver, spleen, and lymphatic system, resulting in cortical atrophy, cherry red spot on macula, HSM

Niemann-Pick disease

AR deficiency of hexosaminidase A on Chromosome 18, leading to the accumulation of GM_2 ganglioside within lysosomes resulting in neurologic degeneration and developmental delay, and cherry red spot on macula

Tay-Sachs disease

AR deficiency of arylsulfatase A, leading to an accumulation of cerebroside sulfate and dysfunction and demyelination of the central and peripheral nervous systems resulting in ataxia and dementia

Metachromatic leukodystrophy

XL recessive deficiency of iduronate sulfatase, leading to an accumulation of heparan and dermatan sulfate resulting in mental retardation, coarse facial features, and short stature

Hunter syndrome

AR deficiency of α-l-iduronidase, leading to the accumulation of partially degraded glycosaminoglycans within lysosomes resulting in dysmorphic, gargoyle-like facies, corneal clouding, HSM, and skeletal abnormalities

Hurler syndrome

AR deficiency of UDP-N-acetylglucosamine: N-acetylglucosaminyl-L-phosphotransferase, loss of protein tagging with mannose-6-phosphate, leading to defective trafficking of enzymes into lysosomes → developmental delay and coarse facial features

I-cell disease (mucolipidosis type II)

Name the genetic disease associated with each of the following clinical or pathologic findings:

Cherry red spot of the macula

Tay-Sachs disease and Niemman-Pick disease

Cells containing “crinkled paper” cytoplasm and glycolipid-laden macrophages

Gaucher disease

Corneal clouding

Hurler syndrome

Carbohydrate, Protein, and Lipid Metabolism

Name the major metabolic pathway regulated by the following enzymes:

Isocitrate dehydrogenase

Citric acid cycle

Phosphofructokinase

Glycolysis

Fructose-1,6-bisphosphatase

Gluconeogenesis

Glycogen synthase

Glyconeogenesis

Glycogen phosphorylase

Glycogenolysis

Glucose-6-phosphate dehydrogenase

Pentose phosphate pathway

Acetyl-coenzyme A (CoA) carboxylase

Lipogenesis

Carnitine acyltransferase

Lipolysis (β-oxidation)

HMG-CoA reductase

Cholesterol synthesis

Name the major activators and/or inhibitors for each of the following enzymes:

Citrate synthase

Activator: no major activator

Inhibitors: ATP, NADH, succinyl-CoA, and acyl-CoA derivatives of fatty acids

Phosphofructokinase-1

Activator: AMP, fructose-2,6-bisphosphate (liver)

Inhibitor: citrate, ATP, and cAMP

Pyruvate dehydrogenase

Activator: CoA, nicotinamide adenine (NAD), adenosine diphosphate (ADP), and pyruvate

Inhibitor: acetyl-CoA, NADH, and ATP

Pyruvate carboxylase

Activator: acetyl-CoA

Inhibitor: ADP

Fructose-1,6-bisphosphatase

Activator: cAMP

Inhibitor: AMP and fructose-2,6-bisphosphate

Glycogen synthase

Activator: glucose-6-phosphate

Inhibitor: no major inhibitor

Glycogen phosphorylase

Activators: cAMP and Ca2+ (muscle)

Inhibitors: glucose, glucose-6-phosphate, and ATP

Glucose-6-phosphate dehydrogenase

Activator: NADP+

Inhibitor: NADPH

Acetyl-CoA carboxylase

Activator: citrate

Inhibitor: malonyl-CoA, palmitoyl-CoA, and cAMP

Carnitine acyltransferase

Activator: no major activator

Inhibitor: malonyl-CoA

HMG-CoA reductase

Activator: no major activator

Inhibitor: cholesterol and cAMP

Describe the effect of insulin on the following metabolic processes:

Glycogen synthesis in muscle and liver

Increase

Gluconeogenesis in the liver

Decrease

Glycogenolysis in the liver

Decrease

Glucose uptake in muscle and adipose tissue

Increase

Triacylglycerol degradation

Decrease

Triacylglycerol synthesis

Increase

Protein synthesis

Increase

Describe the effect of glucagon on the following metabolic processes:

Glycogenolysis in the liver

Increase

Gluconeogenesis in the liver

Increase

β-Oxidation of fatty acids in the liver

Increase

Amino acid uptake by liver

Increase

Which small molecule accepts reducing equivalents and is typically involved in catabolic processes?

NAD+

Which small molecule donates reducing equivalents and is typically involved in anabolic processes?

Nicotinamide adenine dinucleotide phosphate (NADPH)

Name the cellular compartment (cytosol, mitochondria, or both) where each of the following processes occur:

Citric acid cycle

Mitochondria

Fatty acid oxidation

Mitochondria

Fatty acid synthesis

Cytosol

Gluconeogenesis

Both

Glycolysis

Cytosol

Heme synthesis

Both

Hexose monophosphate (HMP) shunt

Cytosol

Protein synthesis

Cytosol (rough ER)

Steroid synthesis

Cytosol (smooth ER)

Urea cycle

Both

Hexokinase or glucokinase?

Found in most tissues

Hexokinase

Found exclusively in the liver and β-islet cells

Glucokinase

High affinity for glucose

Hexokinase

Faster reaction velocity

Glucokinase

Inhibited by glucose-6-phosphate

Hexokinase

Name the molecule(s) that serve as the primary source of energy for the following organs:

Liver

Amino acids, lipids, glucose, fructose, and lactate

Central nervous system (CNS)

Glucose

Heart

Lipids, ketone bodies, lactate, and glucose

Adipose tissue

Glucose and lipids

Type I skeletal muscle fibers (slow twitch, “red”)

Lipids and ketone bodies

Type II skeletal muscle fibers (fast twitch, “white”)

Glucose

What are the four major enzymes that function in gluconeogenesis?

1. P yruvate carboxylase

2. P EP carboxykinase

3. F ructose-1,6-bisphosphatase

4. G lucose-6-phosphatase (Pathway Produces Fresh Glucose)

Name four important cellular processes that require reducing equivalents supplied primarily by the pentose phosphate pathway:

1. Fatty acid and steroid biosynthesis

2. Glutathione-mediated reduction of H_2O_2

3. Cytochrome P-450 system

4. Respiratory burst in phagocytes

Which molecule serves as donor of methyl groups in many metabolic processes?

S-adenosylmethionine

Name four biosynthetic pathways that require methyl group donation by S-adenosylmethionine:

Synthesis of

1. Choline

2. Creatine

3. Epinephrine

4. 7-Methylguanosine

Which metabolic process is responsible for transferring reducing equivalents from RBCs and muscle tissue to the liver?

Cori cycle

Which two amino acids play key roles in the transport of nitrogen from the periphery to the liver?

1. Alanine

2. Glutamine

What are the cofactors for the pyruvate dehydrogenase complex?

B_1, B_2, B_3, B_5, and lipoic acid

Name the eight intermediates of the citric acid cycle:

1. C itrate (Cindy)

2. I socitrate (Is)

3. α-Ketoglutarate (Kinky)

5. Succinyl-CoA (So)

4. S uccinate (She)

6. F umarate (Fornicates)

7. M alate (More)

8. O xaloacetate (Often)

Name a toxin that directly blocks the flow of electrons through the electron transport chain:

Cyanide

Cyanide is a by-product of the metabolism of what antihypertensive?

Nitroprusside

Name a toxin that directly inhibits mitochondrial ATPase:

Oligomycin

Name a toxin that uncouples oxidative phosphorylation by increasing the permeability of the inner mitochondrial membrane:

2,4-Dinitrophenol (DNP)

What are the primary metabolic substrates released by the liver in the fed state and the fasting state?

Very low-density lipoprotein (VLDL) (fed); glucose and ketone bodies (fasting)

Name the apolipoprotein or lipoprotein responsible for each of the following functions:

Activates lecithin-cholesterol acyltransferase

Apolipoprotein A-I

Binds to low-density lipoprotein (LDL) receptor, mediates VLDL secretion

Apolipoprotein B-100

Delivery of cholesterol from the tissues to the liver

High-density lipoprotein (HDL)

Delivery of cholesterol produced by the liver to the tissues

LDL

Delivery of triglycerol absorbed in the small intestine to tissues

Chylomicron

Delivery of triglycerol produced by the liver to tissues

VLDL

Mediates chylomicron remnant uptake

Apolipoprotein E

Serves as a cofactor for lipoprotein lipase

Apolipoprotein C-II

Which enzyme, found in the liver and bone marrow, catalyzes the rate-limiting step of heme synthesis?

Aminolevulinate synthase

What are the major intermediates in the degradation of heme?

Heme → biliverdin → bilirubin → bilirubindiglucuronide (conjugated bilirubin)

Conjugated bilirubin is excreted in which bodily fluid?

Bile

Which compound produced by intestinal bacterial degradation of conjugated bilirubin gives urine its yellow color?

Urobilinogen

Which common physical finding in severe liver disease results from the accumulation of bilirubin (hyperbilirubinemia)?

Jaundice

Name the essential amino acids:

“PriVaTe TIM HALL”: Phe, Val, Trp, Thr, Ile, Met, His, Arg, Leu, Lys

Which amino acids (AAs) are exclusively ketogenic?

Leu and Lys

Which AAs can be ketogenic or glucogenic?

Tyr, Ile, Phe, and Trp

Which AAs are exclusively glucogenic?

All the amino acids not listed in the above two items

Which AAs are negatively charged at physiologic pH (7.4)?

Asp, Glu (the two acidic AAs)

Which AAs are positively charged at physiologic pH (7.4)?

Arg, Lys (the two basic AAs), His also basic but weakly charged at pH 7.4

Which AA is used to carry ammonium from the muscles to the liver?

Alanine

Which small molecule, essential to the excretion of ammonium, is derived from the removal of ammonium from glutamine?

α-Ketoglutarate

What are the intermediates of the urea cycle?

1. Ornithine (Ordinarily)

2. Carbamoyl phosphate (Careless)

3. Citrulline (Crappers)

4. Aspartate (Are)

5. Arginosuccinate (Also)

6. Fumarate (Frivolous)

7. Arginine (About)

8. U rea (Urination)

What is the limiting reagent for hepatic ethanol (EtOH) catabolism?

NAD+

Which metabolic abnormality in chronic alcoholics results from depletion of NAD+ in the liver?

Hypoglycemia (due to inhibition of gluconeogenesis)

Depletion of NAD inhibits which two major metabolic processes?

1. The conversion of pyruvate to lactate

2. Oxaloacetate to malate

In what metabolic state does the liver commonly produce ketone bodies?

During starvation (or diabetic ketoacidosis)

G Proteins

What class of G protein is associated with the following cell surface receptors:

α_1

Q

α_2

I

β_1

S

β_2

S

M_1

Q

M_2

I

M_3

Q

M_4

S

D_1

S

D_2

I

H_1

Q

H_2

S

V_1

Q

V_2

S

Which two second messengers are increased by the activation of a Gq protein?

1. IP3

2. Diacylglycerol (DAG)

Which enzyme is induced by the activation of a Gq protein?

Protein kinase C

Which enzyme is induced by the activation of a Gs protein?

Protein kinase A

Which second messenger is increased by the activation of a Gs protein?

cAMP

Which enzyme is inhibited by the activation of a Gi protein?

Protein kinase A

Which second messenger is decreased by the activation of a Gi protein?

cAMP

Enzymes

What is the shape of the plot of reaction velocity against substrate concentration for enzymes following Michaelis-Menten kinetics?

Hyperbolic

For an enzyme following Michaelis-Menten kinetics, how does halving enzyme concentration affect Vmax??

Vmax will be halved. (Vmax is directly proportional to enzyme concentration for all substrate concentrations.)

What is the shape of a plot of reaction velocity against substrate concentration for enzyme with a single allosteric regulator?

Sigmoid or “S” shaped

Name two important parameters of the cellular environment that directly affect enzyme kinetics:

1. pH

2. Temperature

The inverse of Vmax ((the maximum reaction velocity) for a given enzyme is represented by what point on a Lineweaver-Burk plot?

The y intercept

The inverse of Km (the Michaelis-Menten constant) for a given enzyme is represented by what point on a Lineweaver-Burk plot?

The x intercept

An enzyme with a small Km will have a high or low affinity for its substrate?

High affinity (Km = 1/2Vmax)

How does a competitive inhibitor affect Km?

Increases

How does a noncompetitive inhibitor affect Km?

No effect

How does a competitive inhibitor affect Vm?

No effect

How does a noncompetitive inhibitor affect Km?

Decreases

Cell Cycle

Name the phase of the cell cycle associated with each of the following cellular events:

Quiescence

G_0

Centrosome duplication

S

RNA, protein, organelle synthesis

G_0

DNA, RNA, histone synthesis

S

Release of E2F from Rb

G_1/S transition

Cyclin-dependent kinase (Cdk)-cyclin A and Cdk-cyclin B are active.

G_2/M transition

Cdk-cyclin D and Cdk-cyclin E are active.

G_1/S transition

Chromatin condensation, mitotic spindle formation

M: prophase

Kinetochore assembly

M: prometaphase

Centrosomes move to opposite poles.

M: prophase

Nuclear envelope and nucleolar disappearance

M: prometaphase

Chromosome alignment at metaphase plate

M: metaphase

Kinetochore separation

M: anaphase

Nuclear envelope and nucleolar formation

M: telophase

Cytoplasmic division (cytokinesis)

M: cytokinesis

Most variable phase of cell cycle

G_1

Which two important molecules are involved in the G_1 to S checkpoint?

Rb, p53

What is the significance of p53?

Allows cell to detect DNA defects and repair them before proceeding with replication

Cell Membranes

What are the major categories of molecules that make up the cell membrane?

Cholesterol, phospholipids, sphingolipids, glycolipids, and proteins

Where in the cell membrane are glycoproteins found?

Exclusively in the noncytoplasmic side

What is the effect of increasing the cholesterol content of a cell membrane?

Membrane fluidity is decreased.

NUTRITION

Name the fat-soluble vitamins:

Vitamins A, D, E, and K

Where are these vitamins absorbed?

Ileum

What conditions cause fat-soluble vitamin deficiencies?

Malabsorption syndromes (eg, cystic fibrosis, celiac disease, ileal disease, ileal resection)

Why do toxicities occur more commonly with fat-soluble vitamins?

Fat-soluble vitamins can accumulate in fatty tissues; varying fat content with age leads to different thresholds of toxicity for children versus elderly.

Which prolonged dietary deficiency of protein and calories is characterized by retarded growth and cachexia in children?

Marasmus

Which disease, characterized by protein deficiency with adequate caloric intake, results in retarded growth, anemia, and severe edema?

Kwashiorkor

Name the vitamin(s) associated with each of the following statements:

Composes NAD+ and NADP+

Vitamin B_3 (niacin)

Remains in the body with stores lasting up to 3 to 5 years

Vitamin B_12 (cobalamin)

Important in purine/pyrimidine synthesis

Folate

Important part of visual pigments and epithelial cell differentiation

Vitamin A (retinol)

Antioxidant that delays cataracts and atherosclerosis

Vitamin E (α-tocopherol)

Component of CoA and fatty acid synthase

Vitamin B_5 (pantothenate)

Cofactors for pyruvate-dehydrogenase complex

Vitamins B_1 (thiamine), B_2 (riboflavin), B_3 (niacin), and B_5 (pantothenic acid)

Found only in animal products; Schilling test used to detect deficiency

Vitamin B_12 (cobalamin)

Cofactor for norepinephrine (NE) synthesis and collagen cross-linkage; ↑ Fe absorption

Vitamin C (ascorbic acid)

Cofactor in transamination reactions

Vitamin B_6 (pyridoxine)

Toxicity causes nausea, stupor, and hypercalcemia

Vitamin D

Important in methionine synthesis and isomerization of methylmalonyl-CoA

Vitamin B_12 (cobalamin)

Toxicity causes skin changes, arthralgias, and premature epiphyseal closure, the first sign of toxicity usually CNS changes from edema.

Vitamin A (retinol)

Catalyzes γ-carboxylation of coagulation factors, synthesized by GI flora

Vitamin K

The most toxic vitamin in overdose

Vitamin D

The most common vitamin deficiency in the United States

Folate

Name the vitamin deficiency associated with each of the following findings:

Wernicke-Korsakoff syndrome, beriberi

Vitamin B_1 (thiamine); B_1 = Ber1Ber1

Rickets, osteomalacia, and hypocalcemic tetany

Vitamin D

Neonatal hemorrhage and ↑ prothrombin time (PT)

Vitamin K

Megaloblastic anemia with neurologic dysfunction

Vitamin B_12 (cobalamin)

Dermatitis, diarrhea, and dementia (pellagra)

Vitamin B_3 (niacin)

Deficiency caused by long-term raw egg ingestion

Biotin (avidin in egg whites binds biotin)

Megaloblastic anemia without neurologic dysfunction

Folate

Dry skin, dry eyes, and night blindness

Vitamin A (retinol)

Hemolysis (from RBC fragility) and ataxia

Vitamin E (α-tocopherol)

EEG abnormalities and peripheral neuropathy; caused by isoniazid (INH) and oral contraceptives

Vitamin B_6 (pyridoxine)

Cheilosis, corneal vascularization, and angular stomatitis

Vitamin B_2 (riboflavin)

Neural tube defects during pregnancy

Folate

Scurvy, hemorrhages, and impaired wound healing

Vitamin C (ascorbic acid)

Deficiency caused by Diphyllobothrium latum infection, sprue, pernicious anemia, and Crohn’s disease

Vitamin B_12 (cobalamin)

Name the trace element associated with each of the following statements:

Important in protein synthesis; deficiency causes acrodermatitis and ↑ sense of taste/smell

Zinc

Involved in hemoglobin synthesis; excess caused by ceruloplasmin deficiency

Copper

Cofactor for glutathione peroxidase; deficiency causes cardiomyopathy

Selenium

Involved in collagen cross-linkage; excess causes pulmonary fibrosis

Silicon

Involved in methionine metabolism; deficiency mimics vitamin B_12 deficiency

Cobalt (constituent of cobalamin)

Reduces insulin resistance, glucose tolerance factor

Chromium

GENERAL EMBRYOLOGY

Name the embryonic structure described below:

Consists of the inner cell mass which ultimately gives rise to the fetus

Embryoblast

Consists of the outer cell mass which ultimately gives rise to the placenta

Trophoblast

Derived from embryoblast; clefts form the amniotic cavity

Epiblast

Derived from embryoblast; ultimately forms the yolk sac

Hypoblast

Border between future mouth and pharynx; formed by both hypoblast and epiblast cells

Buccopharyngeal membrane

Produces β-human chorionic gonadotropin (hCG)

Syncytiotrophoblast

Forms the lining of the cytotrophoblast

Extraembryonic somatic mesoderm

Consists of the syncytiotrophoblast, cytotrophoblast, and extraembryonic somatic mesoderm

Chorion

Forms the covering of the yolk sac

Extraembryonic visceral mesoderm

The following developmental milestones occur how long after contraception?

Implantation

Within 1 week

Bilaminar disc

Within 2 weeks

Gastrulation

Within 3 weeks

Formation of the primitive streak and neural plate

Within 3 weeks

Organogenesis, peak of susceptibility to teratogens

Weeks 3 to 8

Limb formation

Week 4

Cardiac contractions begin

Week 4

Male and female genitals can be distinguished.

Week 10

Name the abnormality/abnormalities caused by the following teratogens:

Angiotensin-converting enzyme (ACE) inhibitors

Renal dysgenesis → oligohydramnios, pulmonary hypoplasia, and limb contractures

Tetracycline

Yellow teeth and enamel hypoplasia

Aminogylcosides

Eighth cranial nerve damage → deafness

Oral hypoglycemics

Neonatal hypoglycemia

Warfarin

Craniofacial (nasal hypoplasia) and CNS defects, stillbirth

Dilantin

Fetal hydantoin syndrome: craniofacial and limb defects, mental deficiencies

Valproic acid

Spina bifida

Lithium

Cardiac (Ebstein) anomaly

Isotretinoin

Craniofacial (small ears), CNS, cardiac, and thymus defects

Indomethacin

Constriction of ductus arteriosus

Diethylstilbesterol (DES)

Clear cell vaginal cancer and cervical/uterine malformations in female offspring

Thalidomide

Limb reduction defects

Alcohol

Fetal alcohol syndrome: craniofacial defects (absent philtrum, flattened nasal bridge, and microphthalmia), growth restriction, and brain, cardiac, and spinal defects

Tobacco

Growth restriction, prematurity, low birth weight

Radiation

Growth restriction, CNS defects, and leukemia

Name the embryonic layer that gives rise to each of the following tissues:

Adrenal cortex

Mesoderm

Anterior pituitary

Ectoderm (oral ectoderm/Rathke pouch)

Aorticopulmonary septum

Ectoderm (neural crest)

Autonomic nerves

Ectoderm (neural crest)

Long bones and vertebrae

Mesoderm

Facial bones

Ectoderm (neural crest)

CNS neurons and astrocytes

Ectoderm (neural tube)

Connective tissue

Mesoderm

Epidermis

Ectoderm (surface ectoderm)

Epithelial lining of the GI tract

Endoderm

Myocardium

Mesoderm

Kidneys

Mesoderm

Lens of eye

Ectoderm (surface ectoderm)

Liver parenchyma

Endoderm

Mammary glands

Ectoderm (surface ectoderm)

Melanocytes

Ectoderm (neural crest)

Striated muscle

Mesoderm

Nucleus pulposus

Mesoderm (notochord)

Pancreas

Endoderm

Parafollicular cells of the thyroid

Ectoderm (neural crest)

Retina

Ectoderm (neural tube)

Schwann cells

Ectoderm (neural crest)

Spleen

Mesoderm

Parathyroid

Endoderm

Posterior pituitary

Ectoderm (neural tube)

Thymus

Endoderm

Thyroid

Endoderm

Kidneys, ureters, and gonads

Mesoderm

BASIC PATHOLOGY

Cellular Adaptations

Give the appropriate term for each of the following definitions:

Complete failure of cell production

Aplasia

Relative decrease in cell production

Hypoplasia

Increase in cell size

Hypertrophy

Replacement of one adult (differentiated) cell (epithelial or mesenchymal) type with another adult cell type

Metaplasia

Decrease in cell substance results in a decrease in cell size; may result in decreased tissue/organ size.

Atrophy

Increase of organ/tissue size due to an increase in the number of cells

Hyperplasia

Cell Injury

Name the mechanism of cell injury characterized by each of the following statements:

Mitochondrial dysfunction →↓ cellular ATP → failure of Na+/K+ ATPase, failure of protein synthesis

Ischemic/hypoxic cell injury

Dissociation of ribosomes and polysomes

ATP depletion

Causes lipid peroxidation of membranes

Reactive oxygen species (O_2-free radicals)

Associated with ionizing radiation, UV light, and reperffusion after ischemic injury

Reactive oxygen species (O_2-free radicals)

Prevented by enzymes such as glutathione peroxidase, catalase, and superoxide dismutase

Generation of reactive oxygen species (O_2-free radicals)

Which molecules are released in response to mitochondrial damage?

Cytochrome c and H+

Cytoskeletal abnormalities, ATP depletion, and cell swelling are associated with what key event in cell injury?

Defective membrane permeability

What is the effect of increased cytoplasmic calcium ions in a cell undergoing apoptosis or necrosis?

Activation of ATPase, endonuclease, phospholipase, and proteases

Necrosis/Apoptosis

Classify the following as features of apoptosis or necrosis:

Cellular blebbing and cell shrinkage

Apoptosis

Involves many contiguous cells

Necrosis

Physiologic, programmed cell removal

Apoptosis

Active form of cell death (requires energy consumption)

Apoptosis

Gross, irreversible cellular injury

Necrosis

Involves single cells or groups of cells

Apoptosis

Involution and shrinkage of affected cells and fragments

Apoptosis

Marked inflammatory reaction

Necrosis

Inhibited by bcl-2; facilitated by bax, p53

Apoptosis

State the function of each of the following molecules during apoptosis:

Caspases (cysteine protease)

Protein cleavage

Endonucleases

DNA cleavage

Phosphatidylserine and thrombospondin

Cell surface molecules recognized by phagocytes

Tumor necrosis factor (TNF)-α receptor and FAS (CD95)

Death receptors

Bcl-2 and Bcl-x

Major antiapoptotic proteins

Bad and Bax

Major proapoptotic proteins

Cytochrome c

Activation of procaspase 9

Apoptosis-activating factor-1 (Apaf-1)

Cytoplasmic receptor for cytochrome c

TNF-α

Bindings of this ligand to its receptor induce association with a death domain.

Granzyme B

Activation of the caspase cascade (released by cytotoxic T cells)

Name the type of necrosis characterized by each of the following features:

Enzymatic degradation of tissue seen in abscesses

Liquefactive necrosis

Commonly seen in tuberculous granulomas

Caseous necrosis

Fibrin-like, proteinaceous deposition in arterial walls

Fibrinoid necrosis

Lipase-induced autodigestion of adipose tissue → saponification

Fat necrosis

Interruption of blood supply to organs supplied by end arteries; architecture well preserved

Coagulative necrosis

Results from vascular occlusion; most commonly affects lower extremities or bowel

Gangrenous necrosis

Cell Changes/Accumulations

What type of cellular change is characterized by excess accumulation of intracellular triglycerides?

Fatty change (steatosis)

What type of calcification is caused by hypercalcemia?

Metastatic calcification

What type of calcification occurs in previously damaged tissues?

Dystrophic calcification

Name four endogenous pigments that accumulate in cells:

1. Melanin

2. Bilirubin

3. Hemosiderin

4. Lipofuscin

Name four diseases associated with protein misfolding:

1. Alzheimer disease

2. α-1-Antitrypsin deficiency

3. Cystic fibrosis

4. Amyloidosis

Name the cellular pigment described below:

Accumulates in jaundice

Bilirubin

Identified with Prussian blue dye; can result in organ damage or simple deposition

Hemosiderin

Yellowish, fat-soluble “wear-and-tear” pigment

Lipofuscin

Formed in the epidermis from tyrosine

Melanin

Inflammation

Which three classes of adhesion molecules are involved in inflammation?

1. Selectins (E, P, and L)

2. Immunoglobulin (Ig) family (intercellular adhesion molecule [ICAM], platelet cell adhesion molecule [PCAM])

3. Integrins

What are the five steps in the extravasation of inflammatory leukocytes?

1. Margination

2. Pavementing

3. Tumbling (rolling)

4. Adhesion

5. Transmigration

Which two groups of cell adhesion molecules pair mediate tumbling?

1. Selectins on endothelial cells

2. Sialylated glycoproteins (eg, sialyl-Lewis-X) on leukocytes

Which two groups of cell adhesion molecules pair mediate leukocyte adhesion to endothelial cells?

1. ICAM and vascular cell adhesion molecule (VCAM) (Ig superfamily) on endothelial cells

2. Integrins on leukocytes

Which factors induce endothelial expression of P-selectin?

Platelet activation factor (PAF), histamine, and thrombin

Which factors induce endothelial expression of ICAM and VCAM?

Interleukin (IL)-1 and TNF

Name five chemotactic factors for neutrophils:

1. Bacterial products

2. C5a

3. LTB_4

4. Chemokines (IL-8)

5. Fibrin split (degradation) products

Name five functional responses of leukocytes following their activation:

1. Eicosanoid production

2. Cytokine secretion

3. Generation of reactive oxygen species

4. Degranulation

5. Altered cell adhesion molecule expression

6. Upregulation of receptors (toll-like, G protein-coupled, opsonin, cytokines)

Name two receptors that function in binding and phagocytosis of bacteria:

1. Mannose

2. Scavenger receptors

What term is used to describe the process of coating substances (with Ig or C3b) to facilitate phagocytosis?

Opsonization

Which neutrophil intracellular microbicidial mechanism uses the HMP shunt to generate an oxidative burst?

H_2O_2-myeloperoxidase (MPO)-halide system of bacterial killing

Name two processes associated with impaired leukocyte adhesion:

1. Recurrent bacterial infections

2. Altered wound healing

Decide whether each of the following substances causes vasoconstriction or vasodilation:

Bradykinin

Vasodilation

Thromboxane (TXA)

Vasoconstriction

Prostacyclin (PGI_2)

Vasodilation

Leukotrienes (LTC_4, LTD_4, and LTE_4)

Vasoconstriction

Prostaglandins (PGD_2, PGE_2, and PGF_2)

Vasodilation

Remember: most substances also cause analogous effects on bronchial tone.

Name seven substances that increase vascular permeability:

1. H istamine

2. Serotonin

3. C3a and C5a

4. Leukotrienes (LTC_4, LTD_4, and LTE_4)

5. Bradykinin

6. Nitric oxide (NO)

7. PAF (low concentration)

Which two enzymes stimulate the release of arachidonic acid from membrane phospholipids?

1. Phospholipase A_2

2. Phospholipase C

What are the two major pathways in arachidonic acid metabolism?

1. Cyclooxygenase (COX)

2. Lipoxygenase

What signaling molecules are produced by the COX pathway?

TXA_2 (in platelets), PGI_2 (in endothelial cells), and other prostaglandins (in other tissues)

What are the two major enzymes involved in prostaglandin production?

1. COX-1

2. COX-2

Which cycloxygenase enzyme serves in homeostatic functions?

COX-1

What products does the lipooxygenase pathway produce?

HPETEs and leukotrienes

Which arachidonic acid metabolite is thought to sensitize nerve endings to pain mediators?

PGE_2 (↓ PGE_2 → analgesic effects)

Name four acute-phase responses of inflammation.

1. Systemic effects (fever and leukocytosis)

2. Hepatic synthesis of acute-phase reactants (C-reactive protein [CRP] ferritin, complement, and prothrombin)

3. Synthesis of adhesion molecules

4. Neutrophil degranulation

Which substance links the kinin, coagulation, plasminogen, and complement systems?

Factor XIIa (Hageman factor)

Which group of plasma proteins participates in immune-mediated lysis of cells?

Complement system

Which substance produced by endothelial cells relaxes smooth muscle and inhibits platelet aggregation?

Nitric oxide (NO)

Which factor is a pyrogen and causes fever?

IL-1 → PGE_2

Name four possible outcomes of acute inflammation:

1. Complete resolution

2. Abscess/ulcer/fistula formation

3. Healing by fibrosis and scarring

4. Progression to chronic inflammation

Which pattern of chronic inflammation is characterized by nodular collections of epithelioid histocytes and multinucleated giant cells?

Granulomatous inflammation

Name three etiologies of granulomatous inflammation:

1. Infectious (Mycobacterium tuberculosis, Histoplasma, catscratch disease, leprosy, syphilis)

2. Foreign bodies

3. Idiopathic (eg, sarcoidosis, Crohn’s disease)

Tissue Repair

What are the four factors determining the size of a cell population?

1. Proliferation

2. Cell death

3. Cell differentiation

4. Replacement by stem cells

What are the three categories of cells based on their inherent proliferative activity?

1. Permanent (cardiac myocytes, neurons)

2. Quiescent (hepatocytes, endothelial cells, lymphocytes)

3. Labile (epidermis, GI, and respiratory tract epithelial cells; bone marrow; hair follicles)

Name five factors that mediate cellular proliferation during the process of tissue repair:

1. Platelet-derived growth factor (PDGF)

2. Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α)

3. Fibroblast growth factors (FGFs)

4. Hepatyocyte growth factor

5. Vascular endothelial growth factor (VEGF)

What highly vascular, newly formed connective tissue fills defects left by removal of cellular debris?

Granulation tissue

What are the four key components to the orderly formation of a scar?

1. Angiogenesis and granulation tissue formation

2. Fibroblast emigration and proliferation

3. Deposition of extracellular matrix

4. Maturation and remodeling → scar

Name five factors that delay or impede tissue repair:

1. Impaired circulation

2. Persistent infection

3. Retention of debris or foreign body

4. Nutritional deficiency (eg, proteinand vitamin C)

5. Metabolic disorders (eg, diabetesmellitus)

Hemodynamic Dysfunction

Name five causes of edema:

1. ↑ Hydrostatic pressure

2. ↑ Capillary permeability

3. ↓ Oncotic pressure

4. ↑ Na+ retention (renal disorders or congestive heart failure [CHF])

5. Lymphatic obstruction

Describe the contents of a transudate.

Low-protein content (SG 1.012), few cells, and little protein

What type of fluid accumulation forms as a result of increased vascular permeability due to endothelial cell destruction?

Exudate

What is the composition of exudate?

High protein (SG >1.020) ↑ inflammatory leukocytes, and ↑ protein

Name two organs commonly affected by chronic passive congestion and their related pathologic findings:

1. Lungs: hemosiderin-laden macrophages or “heart-failure cells” (from left heart failure)

2. Liver: nutmeg liver (from right heart failure)

Name the two types of infarcts and several examples of each:

1. Anemic (white) infarcts: heart, spleen, and kidneys

2. Hemorrhagic (red) infarcts: lungs, testes, and GI tract (occurs in areas with collateral circulation)

Thrombosis

What is Virchow triad?

The three primary influences on thrombus formation:

1. Endothelial injury

2. Stasis

3. Hypercoagulability

Name the three components necessary for hemostasis:

1. Vascular endothelium

2. Platelets

3. Coagulation cascade

Name five factors that promote platelet aggregation:

1. ADP

2. Thrombin

3. TXA_2

4. Collagen

5. Platelet-activating factor

Which product of the COX pathway limits further platelet aggregation?

PGI_2

Where are proteins C and S made?

Endothelial cells

Classify the following as features of the extrinsic or the intrinsic pathway:

Involves activation of factor VII

Extrinsic pathway

Clinically monitored by the PT

Extrinsic pathway

Initiated by activation of factor XII

Intrinsic pathway

Monitored by partial thromboplastin time (PTT)

Intrinsic pathway

Name the component(s) of the coagulation cascade associated with each of the following features:

Vitamin K-dependent coagulation factors

Factors II, VII, IX, X, proteins C and S

Ion necessary for proper function of the coagulation cascade

Calcium

Factors inhibited by antithrombin III (AT III)

Thrombin, factors IX, X, XI, and XII

Complex that activates proteins C and S

Thrombomodulin-thrombin complex

The most important fibrinolytic protease

Plasmin

Converts plasminogen to plasmin

Tissue plasminogen activator (t-PA), also urokinase plasminogen activator

Cleaved by activated protein C (APC) → inhibition of coagulation

Factors Va and VIIIa

Which molecule dramatically enhances the activity of AT III?

Heparin

What is the most frequent cause of hereditary thrombophilia?

Factor V (Leiden) mutation (2%-15% of white population)

Hereditary thrombophilia can also be caused by deficiency of what major antithrombotic proteins?

AT III, protein C, and protein S

How does the Leiden mutation confer hypercoagulability?

Renders mutant factor V resistant to cleavage by APC

Which prothrombotic disorder is characterized by autoantibodies that induce platelet activation?

Antiphospholipid antibody syndrome

Name the type of thrombus associated with each of the following:

Reddish-blue cast; usually in lower extremities

Venous thrombosis

Lines of Zahn

Arterial thrombus

Sterile vegetations of heart valves in patients with hypercoagulable states

Nonbacterial thrombotic endocarditis

Noninfective heart valve vegetations from circulating immune complexes

Verrucous (Libman-Sacks) endocarditis

Embolism

Name the type of embolism described by each of the following statements:

Venous thrombus that gains access to arterial circulation through a right-to-left shunt

Paradoxical embolus

Associated with decompression sickness

Air embolus

Occurs at parturition; can lead to disseminated intravascular coagulation (DIC) and death

Amniotic fluid embolus

Embolus obstructing the bifurcation of the pulmonary artery

Saddle embolus

Often arises from one wall of a heart chamber, especially in the context of atrial fibrillation

Mural thrombus → arterial emboli

Important cause of death in immobilized, post-op patients

Pulmonary embolus

Occur after severe, multiple long bone fractures

Fat emboli

Shock

Name the type of shock described by each of the following statements:

Associated with gram-negative endotoxemia

Septic shock

Circulatory collapse from pump failure of left ventricle (LV)

Cardiogenic shock

IgE-mediated systemic vasodilation with ↑ vascular permeability

Anaphylactic shock

Caused by severe hemorrhage or fluid loss

Hypovolemic shock

Associated with severe trauma causing reactive peripheral vasodilation

Neurogenic shock

Which two mediators are associated with systemic vasodilation in septic shock?

1. NO

2. PAF

Name the characteristic manifestations of shock on each of the following organs:

Lungs

Pulmonary edema

Liver

Steatosis and centrilobular necrosis

Colon

Patchy mucosal hemorrhages

Adrenals

Lipid depletion of cortex

Kidneys

Acute tubular necrosis

BASIC PHARMACOLOGY

Absorption/Distribution

In which part of the GI tract are most oral drugs absorbed?

Duodenum

Name three factors that influence absorption of drugs:

1. Chemical properties (active transport vs passive diffusion)

2. pH (percent of drug in the uncharged state determines rate of absorption)

3. Physical factors (blood flow, surface area, and contact time with absorptive surfaces)

What is first-pass metabolism?

Hepatic degradation/alteration of an oral drug after absorption, before it enters the general circulation

Complete the following formulas:

(Rate of drug elimination)/(plasma drug concentration) =

Clearance (CL)

(Amount of drug in body)/(plasma drug concentration) =

Volume of distribution (Vd)

(Cp X Vd)/F =

Loading dose (also defined as the amount of drug necessary to rapidly raise a desired plasma concentration of the drug)

(Cp X CL)/F =

Maintenance dose (also defined as the amount of drug necessary to maintain a desired plasma concentration of the drug)

(0.693 X Vd)/CL =

Cp= target plasma concentration, F = bioavailability

Half-life (t1/2)

If a patient were known to be a rapid metabolizer, would the loading dose or maintenance dose have to be adjusted to maintain a desired plasma concentration of the drug?

The loading dose would be unchanged; the maintenance dose would need to be increased.

How do dosage calculations change for patients with impaired renal/hepatic function?

Loading dose stays the same, maintenance dose decreases.

List four conditions that alter drug distribution:

1. Edematous state (eg, CHF and nephrotic syndrome)

2. Pregnancy (↑ intravascular volume)

3. Obesity (accumulation of lipophilic agents in fat cells)

4. Hypoalbuminemia (no albumin to bind drugs →↑ availability)

Name the key mechanism of drug-drug interactions:

Drug displacement from albumin (combined administration of classes I and II drugs)

Metabolism/Elimination

Name four clinical situations that would result in increased drug half-life.

1. Prerenal state (↓ renal plasma flow)

2. Renal disease → decreased extraction ratio

3. Adding a second drug that displaces the first from albumin, thus ↑ Vd

4. ↓ Metabolism (hepatic insufficiency or drug interaction)

Classify each of the following statements as characteristic of phase I or phase II metabolism:

Produces slightly polar, water-soluble metabolites

Phase I

Involves mixed-function oxidase (P-450)

Phase I

Involves conjugation reactions (acetylation, glucuronidation, and sulfation)

Phase II

Produces very polar, inactive metabolites that are excreted by the kidneys

Phase II

Reduction, oxidation, and hydrolysis

Phase I

Phase that may be compromised first in geriatric patients

Phase I

Phase that may be compromised in neonates

Phase I

Classify each of the following statements as characteristic of first-or zero-order drug elimination:

Constant fraction of drug eliminated per unit of time

First-order elimination

Constant amount of drug eliminated per unit of time

Zero-order elimination

Plasma concentration decreases linearly with time

Zero-order elimination

Plasma concentration decreases exponentially with time

First-order elimination

Elimination rate is independent of concentration

Zero-order elimination

Pharmacodynamics

What term describes the maximum effect a drug can produce?

Efficacy

What term describes the measure of the amount of drug needed to produce a given result?

Potency

What term describes the dose of a drug that produces the desired effect?

Effective dose (ED)

What term describes the dose of a drug that produces death?

Lethal dose (LD)

What term describes the measure of the safety of a drug?

Therapeutic index

How is therapeutic index calculated?

LD_50/ED_50 (LD_50 = dose lethal in 50% of the population, ED_50 = dose effective in 50% of the population)

How does a competitive antagonist affect the dose-response curve?

Shifts it to the right (↑ ED_50)

How does a noncompetitive antagonist affect the dose-response curve?

Shifts it downward (↓ maximal response)

How does a partial agonist differ from a full agonist?

Acts like an agonist when an agonist is not present; acts like an antagonist if an agonist is present

Drug Development

Name the phase of drug development described by each of the following statements:

Measures effect of the drug in patients with a disease

Phase II clinical testing

Measures whether the drug is safe in healthy volunteers

Phase I clinical testing

Postmarketing surveillance

Phase IV

Large, multicenter clinical trials to prove efficacy and safety

Phase III clinical trials

Tox icology

Name the antidote for each of the following toxins:

Iron

Deferoxamine

Copper/gold/arsenic

Penicillamine

Lead

CaEDTA, succimer, dimercaprol (BAL in oil), and oral penicillamine

Arsenic/mercury

Dimercaprol

Carbon monoxide

100% O_2 and hyperbaric O_2

Cyanide

Nitrite, vitamin B_12, and thiosulfate

Methemoglobin

Methylene blue

Methanol/ethylene glycol

ETOH, fomepizole, and dialysis

Acetaminophen (Tylenol)

N-acetylcysteine

Aspirin (salicylates)

Alkalinze urine (promotes excretion) and dialysis

Opioids

Naloxone (IV, IM, and SQ) or naltrexone (PO)

Benzodiazepines

Flumazenil

Organophosphates, anticholinesterases

Atropine and pralidoxime (PAM)

Heparin

Protamine sulfate

Warfarin

Vitamin K, fresh frozen plasma (FFP) for acute reversal

tPA

Aminocaproic acid

Digitalis

Antidig Fab fragments (first stop drug and stabilize K+, Mg2+, and lidocaine)

Cyclophosphamide

Mesna

P-450

Classify each of the following drugs as inhibitors or inducers of P-450:

Inducers: “Queen Barb takes Phen-phen and Refuses Greasy Carbs”

Inhibitors: “Inhibitors Stop Cyber-K ids from Eating Grapefruits”

Barbiturates

Inducer

INH

Inhibitor

Spironolactone

Inhibitor

Rifampin

Inducer

Cimetidine

Inhibitor

Ketoconazole

Inhibitor

Phenytoin and carbamazepine

Inducer

Quinidine

Inducer

Disulfiram

Inhibitor

Sulfonamides

Inhibitor

Steroids

Inhibitor

Macrolides (erythromycin)

Inhibitor

Chloramphenicol

Inhibitor

Griseofulvin

Inducer

Grapefruit

Inhibitor

Verapamil

Inhibitor

Chronic EtOH use

Inducer

Acute EtOH use

Inhibitor

CHAPTER 2

Immunology

IMMUNOLOGY BASICS

Cells of the Immune System

Name the type of immune cell that fits each description given below:

Major cells involved in innate immunity

Monocytes, macrophages, neutrophils, natural killer (NK) cells

Cell-mediated immune response

T lymphocyte

Humoral immunity

B lymphocyte

Primary phagocytic cell in acute inflammation

Neutrophil

Type of cell necessary for transplant rejection

T lymphocyte

Contains myeloperoxidase and lysozyme

Neutrophil

Major mediator of a type 1 hypersensitivity reaction

Mast cell

Major mediator of the antiparasitic response

Eosinophil

Granules contain histamine and heparin

Basophil and mast cells

Major antigen-presenting cells in tissues

Macrophages, dendritic cells, and B cells

Demonstrates a multilobed (“hypersegmented”) nucleus in vitamin B_12 or folate deficiency

Neutrophil

Secretes interleukin (IL)-1 to promote T cell activity

Macrophage

Expresses IgE receptors on its cell membrane to mediate the allergic response

Basophil

Expresses high levels of major histocompatibility complex (MHC) class II on its cell membrane

Macrophage

Macrophage precursor

Monocyte

Cell type increased in atopic asthma

Eosinophil

Recognizes antigen presented in the context of MHC class II molecules

T-helper cell

Antibody-producing cell with abundant rough endoplasmic reticulum

Plasma cell

Major source of IL-2 production

T-helper cell (specifically TH1 cells)

Major cell of the humoral immune response

B lymphocyte

Immunoglobulins

Name the type of immunoglobulin (Ig) associated with the following features:

Most abundant type of Ig

IgG

First class of Ig produced in an immune response upon exposure to antigen

IgM

Able to fix complement

IgG and IgM

Found on the lining of mucous membranes and in secretions, including breast milk and saliva

IgA

Able to cross placenta

IgG

Type of Ig commonly occurring as a dimer

IgA

Type of Ig commonly occurring as a pentamer

I§M

Ig elevated in patients with asthma and allergies

IgE

Responsible for long-term immunity

IgG

Causes mast cells and basophils to release histamine when triggered by antigen

IgE

Type of Ig found embedded in the cell membrane of developing B cells

IgD

Total levels and concentration of this antibody can be estimated using radioimmunosorbent test (RIST) and radioallergosorbent test (RAST).

IgE

What term is used to describe the portion of a molecule that serves as an antigenic determinant?

Epitope

What term is used to describe a small molecule that can serve as an antigenic determinant only if it is attached to a larger carrier molecule?

Hapten

What type of chemical bonds are critical in linking the heavy and light chains of Igs?

Disulfide bonds

Which products result when papain digests an Ig?

Two Fab fragments (each capable of binding antigen) and one Fc fragment

Which products are produced following pepsin digestion of an Ig?

One F(ab’)2 fragment and one Fcfragment

What term is used to describe the region in an antibody that determines antigen specificity?

The hypervariable region or complementarity determining region (CDR)

Name five mechanisms by which antibody diversity is created:

1. Mutations in the genes encoding the CDR region

2. Random VJ recombination in light chains

3. Random VDJ recombination in heavy chains

4. Random assembly of light and heavy chains

5. Imperfect recombination of VDJ genes

T Cells

Name the T-lymphocyte cell surface protein associated with the f ollowing features:

Antigen-specific receptor on 95% of T cells

αβ T-cell receptor (αβ TCR)

Antigen-specific receptor on 5% (or less) of T cells

γδ T-cell receptor (γδ TCR)

Signal transduction protein always associated with TCR

CDS

T-cell marker expressed in immature T cells

CD2

Responds to MHC class II molecule expressed by antigen-presenting cells

CD4

Responds to MHC class I molecule expressed on all cells

CD8

Found specifically on T-helper cells

CD4

Found specifically on cytotoxic T cells

CD8

Cells with this surface marker ↓ in HIV/AIDS

CD4

Type of T cell that destroys virally infected cells

CD8

HLA Subtypes

Name the HLA haplotype(s) associated with the following diseases:

Ankylosing spondylitis

HLA-B27

Type 1 diabetes mellitus

HLA-DR3/DR4

Multiple sclerosis

HLA-DR2

Rheumatoid arthritis

HLA-DR4

Screening for abacavir hypersensitivity

HLA-B*5701

Cytokines

Name the cytokine described below:

Endogenous pyrogen

IL-1 (produced by macrophages)

Promotes IgA synthesis

IL-5

Induces IL-2 production by T cells

IL-1

High concentrations induce cell death in some tumors and cause cachexia.

Tumor necrosis factor (TNF)-α

Induces T- and B-cell activity during the initial stages of an immune response

IL-1

Induces production of IgE and IgG

IL-4 (produced by T-helper cells)

Induces differentiation of eosinophils and promotes growth in B cells

IL-5 (produced by T-helper cells)

Chemotactic factor for neutrophils

IL-8 (produced by monocytes and endothelial cells)

Secreted by activated T cells and induces maturation of bone marrow stem cells

IL-3

Inhibits production of interferon-gamma (IFN-γ) by T-helper cells

IL-10 (produced by TH2 cells)

Inhibits production of IFN-γ

IL-4

Inhibits differentiation of TH1 cells

IL-10

Stimulates TH1 differentiation

IL-12 (produced by macrophages and B cells)

Activates T-helper, T-cytotoxic, natural killer, and B cells

IL-2 (produced by T-helper cells)

Promotes production of IFN-γ T-helper cells

IL-12

Low concentrations promote neutrophil activity and IL-2 receptor expression.

TNF-α

Inhibits growth and function of T and B cells and promotes collagen secretion during tissue repair

Transforming growth factor-beta (TGF-β)

Gel and Coombs Hypersensitivity Reactions

Name the Gel and Coombs hypersensitivity reaction described below:

Mediated by IgE bound to mast cells and basophils

Type 1 (immediate or anaphylactic hypersensitivity)

Antibody-mediated cytotoxic reaction

Type 2 (cytotoxic reaction)

Occurs in response to environmental allergies

Type 1

Antigen-sensitized T cells release cytokines, which induce an inflammatory response up to 48 hours after initial contact with antigen.

Type 4 (delayed-type hypersensitivity)

Associated with the release of histamine, platelet-activating factor, leukotrienes, prostaglandins, and thromboxanes

Type 1

Binding of cytotoxic T cells or complement to Fc portion of antibody causes target cell lysis

Type 2

Immune complex deposition in tissues results in an inflammatory response

Type 3 (immune complex reaction)

Name the type of hypersensitivity reaction responsible for the following diseases or conditions:

Arthus reaction

Type 3

Asthma

Type 1

Chronic transplant rejection

Type 4

Contact dermatitis, reaction to poison ivy

Type 4

Drug allergies

Type 1

Environmental allergies

Type 1

Erythroblastosis fetalis

Type 2

Goodpasture syndrome

Type 2

Graves disease

Type 2

Hemolytic anemia

Type 2

Immune complex-mediated glomerulonephritis

Type 3

Lambert-Eaton

Type 2

Myasthenia gravis

Type 2

Multiple sclerosis

Type 4

Pernicious anemia

Type 2

Purified protein derivative (PPD)/tuberculin skin test

Type 4

Rheumatic fever

Type 2

Rheumatoid arthritis

Type 3

Systemic anaphylaxis

Type 1

Serum sickness

Type 3

Systemic lupus erythematosus (SLE)

Type 3

Transfusion reaction due to ABO incompatibility

Type 2

Complement

Which class of bacteria is particularly susceptible to complement-mediated lysis?

Gram-negative organisms

Which antibody isotypes activate the classic pathway of the complement cascade?

IgG and IgM

Which molecules activate the alternative pathway of the complement cascade?

Aggregated IgA, endotoxin, and other components of the bacterial cell wall

Name the component(s) of the complement cascade responsible for the following functions:

Neutralization of viruses

Cl to C4

Opsonization

C3b

Neutrophil and macrophage chemotaxis

C5a

Synthesis of membrane attack complex (MAC)

C5b to C9

Formation of C3 convertase

C3b, Bb (alternative pathway) or C4b, C2b (classic pathway)

Name the disease or condition caused by a deficiency of the following complement components:

Cl esterase inhibitor

Hereditary angioedema

C3

Sinus and upper respiratory tract infections

C5b to C9

Recurrent Neisseria infections

Decay accelerating factor

Paroxysmal nocturnal hemoglobinuria

Transplant Rejection and MHC Molecules

For each of the following descriptions, name the type of transplant rejection:

Preformed antibodies in host react against graft antigens

Hyperacute rejection (minutes to hours)

Activation of previously sensitized T cells

Accelerated rejection (hours to days)

Involves T-cell activation, differentiation, and antibody production

Acute rejection (days to weeks)

Immune complex deposition combined with subacute cell cytotoxicity

Chronic rejection (months to years)

What are the four different classes of grafts?

1. Autograft (from self)

2. Syngeneic (from identical twin or clone)

3. Allograft (from same species)

4. Xenograft (from different species)

The activity of cytotoxic T cells against tumor or virally infected cells requires which cell surface receptor for antigen presentation?

MHC class I

The activity of cytotoxic T cells against pathogens phagocytosed by macrophages requires which cell surface receptor for antigen presentation?

MHC class II

PATHOLOGY IMMUNE SYSTEM

Autoantibodies

Describe the disease associated with the following autoantibodies:

Antinuclear antibodies (ANA)

SLE (sensitive but not specific for SLE)

Antiacetylcholine esterase (ACh)

Myasthenia gravis

Antibasement membrane

Goodpasture disease

Anticentromere

CREST syndrome (Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly, Telangiectasias)

Anti-dsDNA

SLE (highly specific for SLE)

Antiepithelial cell

Pemphigus vulgaris

Antigliadin

Celiac sprue

Antihistone

Drug-induced lupus

Anti-IgG Fc (rheumatoid factor)

Rheumatoid arthritis

Anti-Jol

Myositis

Antimicrosomal

Hashimoto thyroiditis

Antimitochondrial

Primary biliary cirrhosis

Antinuclear ribonucleoprotein (nRNP)

Mixed connective tissue disease

Antiplatelet

Idiopathic thrombocytopenic purpura

Anti-Scl-70 (DNA topoisomerase 1)

Systemic sclerosis

Anti-Smith

SLE (highly specific for SLE)

Anti-SS-A (Ro) and anti-SS-B (La)

Sjögren syndrome

Antithyroglobulin

Hashimoto thyroiditis

Anti-thyroid-stimulating hormone receptor (TSHr)

Graves disease

Anti-voltage-gated calcium channel

Lambert-Eaton syndrome

Cytoplasmic pattern of antineutrophil cytoplasmic antibodies (c-ANCA)

Wegener granulomatosis

Perinuclear pattern of antineutrophil cytoplasmic antibodies (p-ANCA)

Microscopic PolyANgiitis, Polyarteritis Nodosa (PAN), and Churg-Strauss syndrome

List the four types of nuclear antigens against which ANAs are directed:

1. DNA

2. Histones

3. Nonhistone proteins

4. Nucleolar antigens

Systemic Lupus Erythematosus

What pathologic finding is common to all tissues affected by SLE?

Acute necrotizing vasculitis of small arteries and arterioles caused by immune complex deposition

Describe the effect of SLE on each of the following organs:

Skin

Malar rash, discoid rash, photosensitivity

Joints

Arthritis and arthralgias

Brain

Neuropsychiatric changes or seizures (2° to cerebral vasculitis), cognitive dysfunction

Eyes

Cotton-wool spots, retinal hemorrhages

Heart

Pericarditis, Libman-Sacks Endocarditis (SLE → LSE)

Lungs

Pleuritis, pulmonary fibrosis

Gastrointestinal (GI)

Oral and nasopharyngeal ulcers

Spleen

Splenomegaly and onion skinning of splenic vessels

Kidneys

Wire-loop glomerular lesions and mesangial immune complex deposits → glomerulonephritis

Hematology

Hemolytic anemia, leukopenia, thrombocytopenia, antiphospholipid antibody syndrome

Blood vessels

Raynaud phenomenon

Libman-Sacks endocarditis causes sterile vegetations to form on both sides of which cardiac valve?

Mitral valve

Name five medications capable of inducing a lupus-like syndrome:

1. Hydralazine

2. Isonicotinic acid (INH)

3. Phenytoin

4. Procainamide

5. Penicillamine

Name the disease related to SLE that is characterized by immune complex deposition at the dermal-epidermal junction:

Discoid lupus erythematosus

Immunodeficiencies

Name the immunodeficiency associated with the following clinical and pathologic features:

B-cell deficiency causing recurrent respiratory tract bacterial infections in boys >6 months of age

X-linked (XL) agammaglobulinemia

T-cell deficiency due to failure of development of the third and fourth pharyngeal pouches

Thymic aplasia (DiGeorge syndrome)

Defective B and T cells, most cases caused by XL recessive mutation in γ-chain of cytokine receptors or autosomal recessive (AR) mutation in adenosine deaminase

Severe combined immunodeficiency

AR disease characterized by IgA deficiency, cerebellar dysfunction, and conjunctival telangiectasias

Ataxia-telangiectasia

XL deficiency of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, resulting in an impaired neutrophil respiratory burst and leading to increased bacterial and fungal infections

Chronic granulomatous disease

Recurrent bacterial infections early in life due to a defect in CD40 ligand that prevents B-cell class switching

Hyper-IgM syndrome

AR microtubule defect resulting in decreased phagocytosis, partial albinism, and neuropathy

Chediak-Higashi disease

AR syndrome characterized by failure of neutrophil chemotaxis-associated eczema, elevated IgE, noninf lamed staphylococcal abscesses

Job (hyper-IgE) syndrome

XL recessive disease characterized by recurrent infections, thrombocytopenia, eczema

Wiskott-Aldrich syndrome

Mutation of the Btk tyrosine kinase gene resulting in the underproduction of all classes of antibodies

XL agammaglobulinemia

Defect in the receptor for IL-7

Severe combined immunodeficiency

Associated with Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae respiratory infections and persistent Giardia lambliainfections

XL agammaglobulinemia

Associated with recurrent GI and pulmonary infections

Isolated IgA deficiency

Frequent viral and fungal infections in a patient with hypocalcemia due to low PTH levels

Thymic aplasia (DiGeorge syndrome)

Associated with tetany and congenital defects of the heart and aorta

Thymic aplasia (DiGeorge syndrome)

Small thymus devoid of lymphocytes, hypoplastic lymph nodes, and splenic white pulp

Severe combined immunodeficiency

↑ IgA, normal IgE, and ↓ IgM levels

Wiskott-Aldrich syndrome

Hypogammaglobulinemia commonly due to failure of T-cell-mediated B-cell maturation

Common variable immunodeficiency

Autoimmune Connective Tissue Disorders

Name the autoimmune disease of connective tissue associated with the f ollowing clinical and pathologic findings:

Keratoconjunctivitis sicca or xerophthalmia, xerostomia, and evidence of other connective tissue disease

Sjögren syndrome

Autoimmune inflammatory disorder associated with malignancy; frequently caused muscle weakness

Polymyositis

Heliotrope rash

Dermatomyositis

Rapidly progressive diffuse fibrosis of skin and involved organs including the heart, GI tract, kidney, lung, muscle, and skin

Diffuse scleroderma

CREST syndrome of calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, telangiectasias

Localized scleroderma

↑ Serum creatine kinase (CK) levels

Polymyositis

What is the most common cause of death due to scleroderma?

Renal crisis (accounts for 50% of deaths related to scleroderma)

Which autoimmune disease of connective tissue lacks renal involvement?

Mixed connective tissue disease

Amyloidoses

Name the group of disorders characterized by extracellular deposition of protein in a β-pleated sheet conformation.

Amyloidoses

Which stain is used to identify the presence of amyloid in tissue that exhibits apple green bif ringence under polarized light?

Congo red

Which molecular configuration is common to all forms of amyloid?

Cross-β-pleated sheet

Name the effect of amyloidosis on each of the following organs:

Kidneys

Glomerular, peritubular, and vascular hyalinization

Spleen

Sago spleen (tapioca-like amyloid deposits in follicles) or lardaceous spleen (amyloid deposition in splenic pulp)

Liver

Hepatomegaly with amyloid deposition in the space of Disse

Heart

Restrictive cardiomyopathy

Tongue

Hypertrophy due to amyloid deposition

CHAPTER 3

Microbiology and Infectious Diseases

BACTERIOLOGY

Taxonomy

Name two genera of gram-positive cocci:

1. Streptococcus

2. Staphylococcus

Name four genera of gram-positive bacilli:

1. Clostridium

2. Listeria

3. Bacillus

4. Corynebacterium

Which of these gram-positive bacilli are spore forming?

Clostridium and Bacillus

Which gram-positive cocci are catalase positive (+)?

Staphylococcus

Which of these is also coagulase (+)?

Staphylococcus aureus

Name the streptococci that typically show the following pattern of hemolysis:

α (green/partial hemolysis) “αlmost hemolytic”

Streptococcus pneumoniae and viridans group (eg, Streptococcus mutans)

β (clear hemolysis) “βetter hemolysis”

Group A (Streptococcus pyogenes) and group B (Streptococcus agalactiae)

γ (no hemolysis)

Group D (Enterococcus and Peptostreptococcus)

Laboratory Evaluation of Gram-Positive Bacteria

How are S. pneumoniae and viridans streptococci differentiated in the laboratory?

Streptococcus pneumoniae is bile soluble and optochin sensitive.

How can capsulated S. pneumoniae bugs be detected in the laboratory?

Quellung positive (capsule swells when antisera is added)

What determines the Lancef ield grouping of streptococci?

C-carbohydrate in the bacterial cell wall

How are groups A and B differentiated in the laboratory?

Group A is bacitracin sensitive.

How are spores from gram-positive rods killed?

Autoclave (spores are resistant to heat and most chemicals)

Name the gram-negative organisms associated with each of the following statements:

Three pathogenic gram-negative cocci

1. Neisseria meningitides

2. Neisseria gonorrhea

3. Moraxella catarrhalis

Six gram-negative coccobacilli

1. Haemophilus influenzae

2. Pasteurella

3. Brucella

4. Bordetella pertussis

5. Francisella

6. Legionella

Three clinically important gram-negative rods that are typically lactose fermenting

1. Enterobacter

2. Escherichia coli

3. Klebsiella (all implicated in urinary tract infections [UTIs])

Two obligate intracellular organisms

1. Chlamydia (steals adenosine triphosphate [ATP] from host)

2. Rickettsia (lacks coenzyme A [CoA] and nicotinamide adenine [NAD] → cannot produce own ATP)

Four obligate aerobes

1. Nocardia

2. Pseudomonas

3. Mycobacterium tuberculosis

4. Bacillus

Three obligate anaerobes

1. Clostridium

2. Bacteroides

3. Actinomyces (no catalase and/or superoxide dismutase → susceptible to oxidative damage)

How are the pathogenic Neisseria species differentiated in the laboratory?

Neisseria meningitidis ferments maltose.

How can Pseudomonas be rapidly differentiated from many lactose nonfermenters in the laboratory?

Pseudomonas is oxidase positive.

Provide culture requirements or conditions for each of the following bacteria:

Corynebacterium diphtheriae

Tellurite agar or Loeffler media

Bordetella pertussis

Bordet-Gengou potato blood agar

Neisseria gonorrhoea

Thayer-Martin (VCN—vancomycin, colistin, and nystatin) and a selective medium

Legionella pneumophila

Charcoal yeast agar with iron and L-cysteine

Mycoplasma pneumoniae

Eaton agar

Mycobacterium tuberculosis

Lowenstein-Jensen agar

Vibrio species

Thiosulfate-Citrate-Bile Salts-Sucrose (TCBS) agar

Enterococcus

40% bile and 6.5% NaCl

Haemophilus influenzae

Chocolate agar (contains factor V [NAD] and X [hematin])

Lactose-fermenters (Klebsiella, Escherichia, etc)

MacConkey agar → pink colonies

Fungi

Sabouraud agar

Bacteriology Basics

Which cell membrane structure is unique to gram-positive organisms?

Teichoic acid

Which molecule, unique to the bacterial cell wall, provides rigid support and resistance against osmotic pressure?

Peptidoglycan

Which heat-stable lipopolysaccharide (LPS) is found in the cell wall of gram-negative bacteria?

Endotoxin

Which is the only gram-positive organism with LPS-lipid A?

Listeria monocytogenes

Name five important systemic effects of endotoxin (particularly, lipid A):

1. ↑Interleukin (IL)-1 → fever

2. ↑ Tissue necrosis factor (TNF) → hemorrhagic tissue death

3. ↑ Nitric oxide → hypotension and shock

4. Activation of alternate complement pathway →↑ C3a (edema) and C5a (polymorphonuclear [PMN] chemotaxis)

5. Activation of factor XII → coagulation cascade → DIC

Which has a higher toxicity, endotoxins or exotoxins?

Exotoxins: fatal dose on the order of 1 μg (vs hundreds of micrograms for endotoxins)

Name the mechanism of DNA transfer characterized by the following statements:

DNA is taken up directly from the environment by competent cells

Transformation (can occur in eukaryotic cells, too)

Medically important natural transformers: HHSNG: “Here, Have Some New Genes”: H. pylori, H. influenzae, S. pneumoniae, N. gonorrhoea

Plasmid or chromosomal DNA transferred from one bacterium to another via cell-to-cell contact

Conjugation

DNA transferred by a virus from one cell to another; can be generalized or specialized

Transduction

DNA segments able to excise and reincorporate into different locations

Transposons

Name the bacterium whose exotoxin has the following effects:

Superantigen that induces IL-1 and IL-2 synthesis in toxic shock syndrome; also leads to food poisoning

Staphylococcus aureus

α-Toxin is a lecithinase → gas gangrene

Clostridium perfringens

Prevents the release of the neurotransmitter (NT) glycine from Renshaw cells in spinal cord → paralysis

Clostridium tetani

↑ Adenylate cyclase by adenosine diphosphate (ADP) ribosylation → whooping cough

Bordetella pertussis

Exotoxin encoded by β-prophage; α subunit → inactivates elongation factor 2 (EF-2) halting protein synthesis; β subunit → permits entry into cardiac and neural tissue

Corynebacterium diphtherias

Erythrogenic superantigen → rash in scarlet fever

Streptococcus pyogenes

Prevents release of acetylcholine (ACh) → central nervous system (CNS) paralysis; spores in canned food and honey, construction sites

Clostridium botulinum

Heat-stable toxin ↑ guanylate cyclase; heat-labile toxin ↑ adenylate cyclase by ADP ribosylation of G protein → watery diarrhea

Escherichia coli

Inactivates the 60S ribosome → kills intestinal cells

Shigella dysenteriae

Permanent ADP ribosylation of G protein →↑ adenylate cyclase →↑ Cl- and H_2OO in gut → voluminous stools

Vibrio cholerae

Exotoxin A inhibits protein synthesis by blocking EF-2

Pseudomonas

Which virulence factor allows organisms to colonize mucosal surfaces?

IgA protease (eg, S. pneumoniae and H. influenzae)

Name the bacterial structure associated with each antigenic classification given below:

K-antigen

Capsule (related to virulence of the bacteria)

K = Kapsule

O-antigen

Outer portion of the polysaccharide of endotoxin

O = Outer

H-antigen

Flagella (seen in motile species)

Name the key virulence f actor(s) associated with each of the following organisms:

Group A streptococcus

M-protein, streptokinase, and hyaluronidase

Staphylococcus aureus

Protein A (prevents complement fixation and phagocytosis), penicillinase, and hyaluronidase

Streptococcus viridans

Extracellular dextran → helps bind to heart valves

Yersinia pestis

F1 capsular antigen (antiphagocytic) and protease (degrades clots)

Haemophilus influenzae

Capsule: six types (a-f) and IgA protease

Borrelia

Antigenic variation

Mycobacterium tuberculosis

Mycosides (cord factor, wax D, and sulfatides)

Infectious Diseases

Name the organism(s) associated with each of the following characteristics:

Gram-positive rods with metachromatic granules

Corynebacterium diphtheriae

Three urease (+)

Helicobacter pylori, Proteus, and Ureaplasma urealyticum

Aerosol transmission from environmental water source (eg, air conditioner)

Legionella pneumophila

Contain mycolic acid in membranes

Mycobacterium and Nocardia

Peptidoglycan wall lacks muramic acid

Chlamydiae

Produces pyocyanin (blue-green) pigment

Pseudomonas aeruginosa

Produces yellow-gold pigment

Staphylococcus aureus

Produces reddish pigment

Serratia marcescens

Only bacterial membrane containing cholesterol

Mycoplasma pneumoniae

Filamentous, branching rods in a cervicofacial infection

Actinomyces ismelii

Two forms: elementary and reticulate bodies

Chlamydiae

Pleomorphic gram-negative rods in “school of fish” pattern

Haemophilus ducreyi

Clue cells on wet mount

Gardnerella vaginalis

High liter of cold agglutinins (IgM)

Mycoplasma pneumoniae

Two fungi-like bacteria

Actinomyces israelii and Nocardia asteroides

Name the organism(s) associated with the following pathology:

Fitz-Hugh and Curtis syndrome

Chlamydia trachomatis or N. gonorrhea

Invades gastrointestinal (GI) mucosa → diarrhea; motile; can disseminate hematogenously

Salmonella

Infected dog or cat bites (or scratches)

Pasteurella multocida

Ghon complex

Mycobacterium tuberculosis (1° tuberculosis [TB]). Note: hilar nodes plus Ghon focus usually in lower lobe

Meningitis and pneumonia in neonates

Haemophilus influenzae

Atypical pneumonia with avian reservoir

Chlamydia psittaci

Gas gangrene in traumatic open wounds

Clostridium perfringens

Infects skin and superficial nerves

Mycobacterium leprae

Fibrocaseous cavitary lung lesion

Mycobacterium tuberculosis (2° TB). Note: usually at apex because ↑ affinity for ↑ O_2 environments

Mycobacterium causing disseminated disease in acquired immunodeficiency syndrome (AIDS) patients

Mycobacterium avium-intracellulare

Mycobacterium causing cervical lymphadenitis in kids

Mycobacterium scrofulaceum

For each of the following clinical findings, name the organism responsible and the drug(s) of choice:

Oral/facial abscesses with sulfur granules in sinus tracts

Actinomyces israelii——penicillin G (IV)

Currant jelly sputum

Klebsiella—first- or second-generation cephalosporins

Woolsorter’s disease

Bacillus anthracis—penicillin G or ciprofloxacin

Scarlet fever, impetigo, and pharyngitis

Streptococcus pyogenes—penicillin

Pontiac fever

Legionella pneumophila—macrolide (erythromycin and azithromycin)

Gram-positive coccus causing sepsis/meningitis in a newborn

Streptococcus agalactiae—ampicillin (Note: group B, think Babies)

Acute epiglottitis, meningitis, otitis, and pneumonia

Haemophilus influenzae—second-generation cephalosporins (treat meningitis with ceftriaxone, plus rifampin for contacts)

Gastritis and ~90% of duodenal ulcers

Helicobacter pylori—triple therapy

Waterhouse-Friderichsen syndrome

Neisseria meningitidis—ceftriaxone

Pneumonia in cystic fibrosis and burn patients

Pseudomonas cepacia—bactrim or ciprofloxacin

Bacterial vaginosis with discharge and fishy odor

Gardnerella vaginalis—metronidazole

Burn and wound infections with fruity odor

Pseudomonas aeruginosa—aminoglycoside plus antipseudomonal (eg, piperacillin and tazobactam)

Acute postinf ectious glomerulonephritis

Streptococcus pyogenes—penicillin G

Pseudomembranous enterocolitis

Clostridium difficile—metronidazole or oral vancomycin

Atypical “walking” pneumonia in young adult

Mycoplasma pneumoniae—erythromycin or doxycycline

Urethritis/pelvic inflammatory disease (PID), neonatal conjunctivitis, and pneumonia

Chlamydia tmchomatis types D to K—erythromycin eye drops in neonates, azithromycin for urethritis, pneumonia

Lyme disease

Borrelia burgdorferi—doxycycline

Malignant, vesicular papules covered with black eschar → bacteremia and even death

Bacillus anthracis—penicillin G or ciprofloxacin

Pneumonia, sepsis, otitis externa, UTIs, hot-tub f olliculitis, osteomyelitis

Pseudomonas aeruginosa—aminoglycoside plus antipseudomonal piperacillin and tazobactam

Undulant fever, Bang disease

Brucella sp.—doxycycline plus gentamicin or rifampin (pasteurize milk to prevent)

Bubonic plague

Yersinia pestis—gentamicin

Rocky Mountain spotted fever

Rickettsia rickettsii—tetracycline /doxycycline

Trench fever (lasts 5 days; recurs in 5-day cycles)

Bartonella quintana—gentamicin/doxycycline

Tabes dorsalis, aortitis, and gummas

Treponema pallidum (3° syphilis)—penicillin G

Q fever (acute)

Coxiella burnetii—doxycycline

Weil disease

Leptospira interrogans—penicillin G

Yaws

Treponema pertenue—penicillin G

Pott disease

Mycobacterium tuberculosis (disseminated)—four-drug anti-tuberculous therapy, including rifampin plus isoniazid (INH)

Dental caries

Streptococcus mutans—amoxicillin or amoxicillin/clavulonic acid (prevention with topical fluoride/chlorhexidine)

Rheumatic fever

Streptococcus pyogenes—penicillin G

Scalded skin syndrome and toxic shock syndrome

Staphylococcus aureus—penicillin agent (vancomycin if methicillin-resistant S. aureus[MRSA])

Hansen disease

Mycobacterium leprae—dapsone plus clofazimine or rifampin

What is the differential for a rash affecting the palms and soles?

Rocky Mountain spotted fever, 2° syphilis, hand-foot-and-mouth disease (coxsackie A), and Kawasaki syndrome

Name the mode of transmission and reservoir(s) for each of the following bacteria:

Brucella sp.

Contact with animals or dairy products; cows

Francisella tularensis

Tick or deerfly bite; rabbits and deer

Pasteurella multocida

Animal bite/scratch; cats and dogs

Borrelia burgdorferi

Ixodes tick bite; lives on deer and mice

Yersinia pestis

Flea bite; rodents (eg, prairie dogs)

Rickettsia rickettsii

Tick bite; dogs, rabbits, and rodents (endemic to eastern United States)

Rickettsia prowazekii

Human body louse; humans and flying squirrels

Name the laboratory test described below:

Detects antirickettsial antibodies

Weil-Felix reaction (cross-reacts with proteus)

Sensitive for treponemes

Fluorescent treponemal antibody-absorption test (FTA-ABS) (+) (earliest and longest, used as confirmatory test for syphilis if RPR is reactive)

Useful in screening for TB

Purified protein derivative (PPD) test

Name the screening test for syphilis and four biological false positives:

VDRL test

1. Viruses (mononucleosis and hepatitis)

2. Drugs (narcotics)

3. Rheumatoid arthritis/fever

4. Leprosy and lupus

Name the normal, dominant flora for each of the f ollowing locations:

Nose

Staphylococcus aureus

Oropharynx

Group D streptococci (viridans)

Dental plaques

Streptococcus mutans

Colon

Bacteroides fmgilis > E. coli

Vagina

Lactobacillus; colonized by E. coli and group B streptococcus

Skin

Staphylococcus epidermidis

Name the nosocomial pathogen(s) associated with each of the following:

Urinary catheter

Escherichia coli and Proteus mirabilis

Respiratory therapy equipment, ventilators

Pseudomonas aeruginosa

Wound infections

Staphylococcus aureus

Water aerosols

Legionella sp.

Tuberculosis

Decide whether each of the f ollowing statements is more closely associated with 1° or 2° TB:

Radiographic finding = Ghon complex; classically affects lower lobes

1°TB

Miliary TB

2°TB

Fibrocaseous cavitary lung lesion; classically affects apical lungs (↑ affinity for ↑ O_2 environment)

2°TB

Symptoms of cough/hemoptysis, fever, night sweats, and weight loss

2°TB

What type of hypersensitivity reaction is seen after infection with M. tuberculosis?

Type IV or delayed-type hypersensitivity (basis for PPD test)

What unique type of cell is seen in association with caseating granulomas in TB?

Langerhans giant cell

What is the mode of transmission of M. tuberculosis!

Respiratory droplets

What term describes the lymphatic and hematogenous spread of TB, causing numerous small foci of infection in extrapulmonary sites?

Miliary TB

Name five common sites of extrapulmonary TB:

1. CNS (tuberculous meningitis)

2. Vertebral bodies (Pott disease)

3. Psoas major muscle → abscess

4. GI tract (liver and cecum)

5. Cervical lymph nodes →scrofuloderma

What is an effective screening tool for latent TB?

PPD test

How is active TB infection diagnosed?

Clinical and radiologic signs of 2° TB and acid-fast bacilli in sputum

What is the management of PPD + latent TB?

Treatment with INH + pyridoxine (vitamin B_6) for 9 months

What is the treatment for active TB?

Respiratory isolation and initial four-drug therapy (RIPE: Rifampin, INH, Pyrizinamide, Ethambutol)

What is the major toxicity of most TB drugs?

Hepatotoxicity; INH → vitamin B 6deficiency; ethambutol → optic neuritis

ANTIBIOTICS

Name the drug(s) whose mechanism of action is described below:

Binds penicillin-binding proteins →inhibits transpeptidase → blocks cell wall synthesis; also releases autolytic enzymes (bactericidal)

β-Lactam antibiotics (penicillin, cephalosporins, cephalomycins, carbapenems, and monobactams)

Forms reactive cytotoxic metabolites inside cell

Metronidazole

Binds and inactivate β-lactamase → protects antibiotic

β-Lactamase inhibitors

Inhibits 50S peptidyl transferase

Chloramphenicol

Blocks entry of aa-tRNA to 305 ribosomal complex

Tetracyclines

Blocks transpeptidation of D-ala Inhibits dihydrof olate reductase

Vancomycin

Inhibits dihydrofolate reductase

Trimethoprim (TMP)

Para-aminobenzoic acid (PABA) antimetabolites →↓ dihydropteroate synthase

Sulfonamides

Binds to 30S subunit → block formation of 70S initiation complex → misreading of mRNA

Aminoglycosides

Binds to 50S subunit → inhibit translocase

Macrolides (erythromycin and azithromycin)

Blocks DNA topoisomerase (gyrase)

Quinolones (ciprofloxacin and levofloxacin)

Blocks 50S peptide bond formation

Clindamycin

Inhibits DNA-dependent RNA polymerase

Rifampin

Interferes with mycolic acid synthesis

INH

Bind to bacterial/fungal cell membranes → disrupt osmotic properties

Polymyxins

PABA antagonist → blocks purine synthesis

Sulfones (dapsone and sulfoxone)

Name the antibacterial drug(s) associated with each of the following unique toxicities:

Kernicterus in infants

Sulfonamides and ceftriaxone

Interstitial nephritis

Penicillins

Disulfiram-like reactions

Metronidazole, second-generation cephalosporins

Photosensitivity rash

Doxycycline

Gray baby syndrome

Chloramphenicol

Megaloblastic anemia

IMP

Hemolytic anemia in G6PD-def icient patient

Sulfonamides, chloramphenicol, nitrofurantoin, and INH

Hepatotoxicity, vitamin B_6deficiency, lupuslike syndrome

INH (Note: ↑ t1/2 in slow acetylators)

Pseudomembranous colitis

Clindamycin (most common)

Fanconi syndrome

Tetracycline (ingestion of expired drug)

Ototoxicity and nephrotoxicity

Aminoglycosides

Red, pruritic rash on torso with rapid IV infusion (red man syndrome)

Vancomycin

Reversible cholestatic hepatitis; ↑ GI motility

Erythromycin

Achilles tendonitis; cartilage damage in laboratory animals

Fluoroquinolones

Red-orange discoloration of bodily secretions

Rifampin

Discolors teeth; suppresses bone growth in kids

Tetracycline

Aplastic anemia (dose independent)

Chloramphenicol

Neurotoxicity and nephrotoxicity

Polymyxins

Name six uses for metronidazole:

1. Giardia

2. Entamoeba

3. Trichomonas

4. Gardnerella vaginalis

5. Anaerobes (C. difficile, bacteroides)

6. Helicobacter pylori (part of triple therapy)

Which drug is used as solo prophylaxis for TB?

INH

How do organisms develop resistance against vancomycin?

D-lac (or D-ser) replaces terminal D-ala in cell wall → ↓ affinity of vancomycin for cell wall

VIROLOGY

Taxonomy/Basics

Name six medically important DNA viral families:

HHAPPPy:

1. Hepadnaviridae

2. Herpesviridae

3. Adenoviridae

4. Poxviridae

5. Parvoviridae

6. Papovaviridae

Name two families of circular DNA viruses:

1. Papovaviridae

2. Hepadnaviridae

Name the only ssDNA viral genome:

Parvovirus

Name the only DNA virus that replicates in the cytoplasm:

Poxviridae (carries its own DNA-dependent RNA polymerase)

Name three naked DNA viruses:

PAP:

1. Parvo

2. Adeno

3. Papov

Name the only dsRNA viral genome:

Reoviruses (eg, rotavirus)

Name the family of the smallest RNA viruses:

Picornaviruses

Name four families of naked RNA viruses:

CRAP:

1. Calicivirus

2. Reovirus

3. Astrovirus

4. Picornavirus

Name two families of RNA viruses that do not replicate solely in the cytoplasm:

1. Influenza viruses

2. Retroviruses

Where do most enveloped viruses acquire their membranes?

From plasma membrane (except herpesviruses—nuclear membrane)

Name four families of segmented viruses:

BOAR (all RNA viruses)

1. Bunyaviridae

2. Orthomyxoviridae (influenza viruses)

3. Arenaviridae

4. Reoviridae

Name the only diploid viruses:

Retroviruses

What types of nucleic acids do not require special enzymes to be infectious?

Those with same structure as host nucleic acids (eg, positive-stranded ssRNA and most naked dsDNA)

Name the type of viral genetic strategy described below:

The virus contains its own genetic material but is coated with surface proteins from another virus, which determine its inf ectivity

Phenotypic mixing

Occurs when viruses exchange segments of their genomes

Reassortment

Occurs when a nonmutated virus assists a mutated one by making a functional gene product that serves both itself and the mutated virus

Complementation

Exchanging oligonucleotides by crossing-over within base sequences

Recombination

What type of antigenic change in the influenza virus causes epidemics?

Antigenic drift (minor changes from random mutation)

What type of antigenic change in the influenza virus causes pandemics?

Antigenic shift (reassortment of genome, including animal acquisition)

(Drifting is a Slow Process, Shifting is a Rapid Process)

For each of the following vaccines, state whether it is live attenuated or killed:

Sabin polio

Live attenuated

Salk polio

Killed (SalK = Killed)

May revert to virulence

Live attenuated (very rare)

For whom is it dangerous to receive live vaccines?

Immunocompromised hosts (ie, transplant recipients, AIDS patients, and pregnant women)

Infectious Diseases

Name the virus(es) associated with each of the following statements:

Tzanck prep shows multinucleated giant cells

Herpes simplex virus (HSV)-l, HSV-2, and varicella-zoster virus (VZV)

Viral culture with buffy coat

Cytomegalovirus (CMV)

Transmitted by bat, raccoon, and skunk bites

Rabies virus

Transmitted by arthropods

Arboviruses

Cowdry type A inclusion bodies

Herpesviruses (HSV-1, CMV, and VZV)

Number 1 cause of diarrhea in kids 3 years old (y/o)

Rotavirus

Number 1 cause of viral pneumonia in infants 6 months

Respiratory syncytial virus (RSV)

Severe (but rare) seqealae include giant cell pneumonia and subacute sclerosing panencephalitis (SSPE)

Measles virus (rubeola)

Councilman bodies in liver

Yellow fever virus

Reactivation of virus in brain of AIDS patient → demyelination, death

JC virus → progressive multifocal leukoencephalopathy (PML)

Bullet-shaped, helical nucleocapsid; travels up nerve axons to CNS in retrograde fashion

Rabies virus

Koplik spots

Measles virus (rubeola)

Dane particle

Hepatitis B virus

Atypical lymphocytes

Epstein-Barr virus (EBV) and CMV

Nosocomial infection associated with the newborn nursery

CMV and RSV

Negri bodies in neurons

Rabies virus

Incomplete RNA virus → requires envelope

Hepatitis D virus

Positive heterophile antibody test

EBV

Necrosis of large motor neurons in anterior horn spinal cord → flaccid paralysis

Poliovirus

For each of the following clinical findings, name the associated virus:

Shingles

VZV

Suboccipital lymphadenopathy

Rubella virus

Herpangina, hand-foot-and-mouth disease

Coxsackie A virus

Gingivostomatitis, keratitis, and temporal lobe encephalitis

HSV-1

Genital and neonatal infections

HSV-2

Fever, hepatosplenomegaly pharyngitis, and posterior auricular lymphadenopathy; “kissing disease”

EBV (mononucleosis)

Common cold

Rhinoviruses (>100 serotypes; associated with 85% of cases)

PML

JC polyomavirus

Chickenpox

Varicella

Small, pearly, umbilicated papular epidermal growths near genitals

Molluscum contagiosum virus

German measles and congenital infections

Rubella virus

Explosive gastroenteritis; recent epidemics on cruiseships and schools

Norwalk virus

Exanthem subitum (roseola)

Human herpesvirus (HHV)-6

Contains hemagglutinin and neuraminidase virulence factor; undergoes antigenic shift and responsible for pandemics

Influenza A

Fever, black vomitus, and jaundice; transmitted by Aedes mosquito

Yellow fever virus

Pericarditis, myocarditis, and pleurodynia

Coxsackie B virus

Acute viral hepatitis

Hepatitis A and B

Mononucleosis, congenital infection, and pneumonia

CMV

Subacute sclerosing panencephalitis (SSPE)

Measles (rubeola) virus

Intussusception from hyperplasia of Peyer patches

Adenoviruses

Kaposi sarcoma

HHV-8

Aseptic meningitis, orchitis, and parotitis

Mumps virus

Barking cough and laryngeal swelling

Parainfluenza viruses (croup)

Hepatitis from IV drug abuse or blood transfusion

Hepatitis C virus

Hydrophobia, seizures, and fatal encephalitis

Rabies virus

Cause of common and genital warts

Human papillomavirus (HPV)

Tropical spastic paresis

Human T-cell leukemia/lymphoma virus (HTLV)

Hepatitis with high mortality rate in pregnant women

Hepatitis E virus

Reye syndrome

Influenza viruses (occurs with aspirin [ASA] ingestion)

Epidemic keratoconjunctivitis; childhood URIs

Adenoviruses

Cough, coryza, and conjunctivitis

Measles (rubeola) virus

Erythema infectiosum (fifth disease); transient aplastic anemic crisis

Parvovirus B19

Name the oncogenic virus associated with the following cancers:

Burkitt lymphoma

EBV

Hepatocellular carcinoma

Hepatitis B and C viruses

Hairy cell leukemia

HTLV-2

Adult T-cell lymphoma

HTLV-1

Nasopharyngeal carcinoma

EBV

Kaposi sarcoma

HHV-8

Cervical, penile, and anal carcinoma

HPV types: 16,18, 31, 33, and 45

Name the family of viruses characterized by the following:

Smallpox, molluscum contagiosum, and vaccinia

Poxviridae

Hantavirus and California encephalitis

Bunyaviridae

Marburg and Ebola hemorrhagic fever

Filoviridae

Lassa fever and lymphocytic choriomeningitis

Arenaviridae

Human Immunodeficiency Virus

Which continent has the highest incidence (and prevalence) of AIDS?

Africa

What are the three major routes of HIV transmission?

1. Sexual contact

2. Vertical (mother to newborn) transmission

3. Parenteral

What is the most common mode of HIV transmission on a global basis?

Heterosexual contact

What type of virus is HIV?

Human retrovirus of the lentivirus family

What test is used to screen for HIV infection?

Enzyme-linked immunosorbent assay (ELISA) looks for AB to viral proteins; ↑ sensitivity.

What test is used to confirm HIV(+) screening results?

Western blot assay (high false negative within 2 months of infection); ↑ specificity

Which enzyme creates dsDNA from RNA for integration into host genome?

Reverse transcriptase (RT)

What test is used to monitor the effects of antiretroviral therapy?

HIV RT-polymerase chain reaction (RT-PCR) (measures viral load)

What is the strongest measure of disease progression in an HIV(+) patient?

CD4+ T-cell count

Name two key glycoproteins on the surface of the HIV viral envelope:

1. gp41 (fusion)

2. gp120 (attachment) proteins; together = gp160

Name two key HIV viral core proteins:

1. p24 (nucleocapsid)

2. p17 (matrix protein)

Name three key HIV retroviral enzymes contained in the core:

1. RT

2. Integrase

3. Protease (all encoded by pol gene)

Which viral antigen peaks within 2 months of infection, then rises again years later?

p24

What are the two cell surface molecules to which gpl20 must bind?

1. CD4

2. A chemokine receptor (CCR5 or CXCR4)

HIV infects which three cell types?

1. CD4+T cells

2. Monocytes/macrophages

3. Dendritic cells

The induction of what cellular transcription factor during an immune response leads to activation of transcription of HIV proviral DNA?

Nuclear factor-kappa B (NF-KB)

Protease inhibitors of HIV prevent cleavage of the protein product of what viral genes?

Gag and pol genes

What are the three mechanisms by which HIV-infected CD4+ T cells are lost?

1. HIV cytopathic effect

2. Apoptosis

3. HlV-specific cytotoxic T-cell killing

What are the three stages of HIV infection?

1. Acute retroviral infection

2. Chronic phase

3. AIDS

What is the surrogate measure of viral load in an HIV(+) patient?

HIV-1 RNA

What is the strongest measure of disease progression in AIDS?

CD4+ T-cell count

Which tissues are the major reservoirs of HIV-infected T cells and macrophages in patients?

1. Lymph nodes

2. Spleen

3. Tonsils

Which cell type in the brain is infected by HIV?

Microglial cells

List the major immune abnormalities in AIDS:

1. Decreased number of CD4+ T cells

2. Decreased T-cell function

3. Polyclonal activation of B cells

4. Altered macrophage function

What is the clinical picture of direct viral disease from HIV?

Constitutional symptoms (weight loss, fever, fatigue, and night sweats) and/or neurologic symptoms (encephalopathy with dementia and aseptic meningitis)

How is AIDS defined?

CD4+ 200 or AIDS-defining illness, regardless of CD4+ count

Name the common AIDS opportunistic organisms or infections/diseases associated with the following:

Four fungal infections

1. Candidiasis (GI tract)

2. Cryptococcosis (meningitis)

3. Histoplasmosis (disseminated)

4. Coccidioidomycosis (disseminated)

Five bacterial infections

1. Mycobacterium tuberculosis (lung/disseminated)

2. Mycobacterium avium-intracellulare (lung)

3. Nocardia (lung/CNS/disseminated)

4. Salmonella (disseminated)

5. Encapsulated organisms

Four viral infections

1. HSV

2. VZV (shingles)

3. CMV (retinitis or colitis)

4. JC virus (PML)

Three protozoal infections

1. Pneumocystis (lung or disseminated)

2. Toxoplasm (lung/CNS)

3. Cryptosporidium (GI)

State the typical CD4+ count associated with each of the following HIV complications:

Opportunistic infections are typically seen, especially Pneumocystis jiroveci pneumonia

200 cells/mL

Mycobacterium avium complex (MAC), CMV, and cryptosporidiosis

50 cells/mL

Toxoplasmosis

100 cells/mL

TB becomes more common

400 cells/mL

List four common neoplasms in patients with AIDS:

1. Kaposi sarcoma

2. Non-Hodgkin B-cell lymphoma

3. CNS lymphoma

4. Squamous cell carcinoma of the cervix or anus

What has been shown to minimize the risk of perinatal HIV transmission?

Zidovudine (AZT) given to pregnant women, cesarean delivery, and avoiding breast feeding

Prions

Which infectious agents lack both DNA and RNA?

Prions (made of proteins only)

What are symptoms of prion diseases?

Rapidly progressing dementia, psychiatric disturbances, and cerebellar symptoms (ataxia, myoclonis). All prion diseases are fatal.

Name four prion diseases:

1. Creutzfeldt-Jacob disease (rapidly progressive dementia)

2. Mad cow disease

3. Kuru

4. Fatal familial insomnia

What type of histopathologic change is seen in these diseases?

Spongiform encephalopathy

ANTIVIRAL AGENTS

For each of the following drugs, provide:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects and uniquetoxicity (TOX) (if any):

Acyclovir and valacyclovir

MOA: guanosine analog; activated by herpes thymidine kinase → inhibits viral DNA polymerase

IND: HSV (treatment and prophylaxis for oral, genital, and ocular herpes), VZV (chickenpox and shingles)

TOX: neurotoxic (delirium and tremors) and nephrotoxic

Ganciclovir

MOA: guanosine analog; activated by human thymidine kinase → inhibits CMV DNA polymerase

IND: CMV (retinitis, pneumonia, colitis), especially in immunocompromised people

TOX: bone marrow suppression, nephrotoxic, and ↓ spermatogenesis (toxicity → acyclovir because activated by human enzyme)

Foscarnet

MOA: pyrophosphate analog; inhibits viral DNA polymerase (no activation required)

IND: CMV, HSV (refractory infections)

TOX: reversible nephrotoxicity and anemia

Nucleoside RT inhibitors (zidovudine—azidothymidine [AZT], didanosine—ddl, zalcitabine—ddC, lamivudine-3TC, and stavudine—d4T)

MOA: nucleoside analogs; activated by phosphorylation → inhibits RT → prevents incorporation of viral genome into host DNA

IND: part of combination therapy for HIV

TOX: bone marrow suppression, peripheral neuropathy, pancreatitis (especially ddl), lactic acidosis, and macrocytic anemia (AZT)

Nonnucleoside RT inhibitors (nevirapine, delavirdine, and efavirenz)

MOA: binds directly to and inhibits HIV RT → prevents incorporation of viral genome into host DNA

IND: part of combination therapy for HIV

TOX: rash (including Steven-Johnson), ↑ liver enzymes, inhibits P-450, vivid dreams/CNS changes (with ef avirenz)

Protease inhibitors (saquinavir, ritonavir, indinavir, nelf inavir, and amprenavir)

MOA: blocks protease enzyme → inhibits assembly of viral core and new viruses

IND: part of combination therapy for HIV

TOX: GI upset, insulin resistance, ↑ lipids, fat redistribution syndromes, interstitial nephritis, and thrombocytopenia (indinavir)

Amantadine and rimantadine

MOA: inhibits viral penetration and uncoating; releases dopamine (DA) from intact nerve terminals

IND: influenza A treatment/prophylaxis, Parkinson disease

TOX: CNS effects: confusion, ataxia, and slurred speech (less with rimantadine); teratogenesis

Zanamivir and oseltamivir

MOA: neuraminidase inhibitor → alters virion aggregation and release

IND: influenza A and B treatment and prophylaxis (oseltamivir)

TOX: bronchospasm in patients with asthma /COPD) (zanamivir)

Ribavirin

MOA: guanosine analog; activated by phosphorylation → inhibits inosine-5’-monophosphate (IMP) dehydrogenase

IND: RSV, hantavirus, and chronic hepatitis C

TOX: hemolysis (when given IV)

Interferon-α

MOA: human glycoproteins that interfere with ability of viruses to replicate (block protein synthesis and degrade mRNA)

IND: chronic hepatitis B and C, genital warts, Kaposi sarcoma, and hairy cell leukemia

TOX: bone marrow suppression

What constitutes highly active antiretroviral therapy (HAART)?

Two nucleoside RT inhibitors and a protease inhibitor or nonnucleoside RT inhibitor. Note: no patient should ever be on monotherapy as resistance is invariable.

When is HAART typically initiated?

CD4+ 500 cells/mL or very high viral load

Which drug is used to prevent vertical transmission during pregnancy?

Zidovudine (AZT)

MYCOLOGY

Which four endemic mycoses can mimic TB?

1. Histoplasmosis

2. Coccidioidomycosis

3. Paracocidioidomycosis

4. Blastomycosis

What is a dimorphic fungus?

Lives in two forms: cold = mold (37°C), heat = yeast

Name the fungus associated with each of the following statements:

“Spaghetti and meatball” appearance on KOH prep

Malassezia furfur

Contains cancer-causing aflatoxins

Aspergillus flavus

Dimorphic fungus living on rose thorns and splinters

Sporothrix schenckii

Urease (+), stains with India ink, and latex agglutination (+)

Cryptococcus neoformans

Organism found inside macrophages; spread in pigeon and bat droppings

Histoplasma capsulatum

Budding yeast, pseudohyphae; germ tubes at 37°C

Candida albicans

Wide angle (90°) branching of irregular nonseptated hyphae

Mucor and Rhizopus sp.

Big, broad-based budding dimorphic fungus

Blastomycosis

B-B-B-B-B (Big, Broad-Based Budding Blasto)

45° angle branching and septated hyphae; fruiting bodies

Aspergillus sp.

Narrow-based unequal budding yeasts with capsular halo

Cryptococcus neoformans

Endemic to Ohio and Mississippi river valleys

Histoplasma capsulatum

”Flying-saucer” appearance of silver stain

Pneumocystis carinii (also P. jiroveci)

”Captain’s wheel” appearance; endemic to rural Latin America

Paracoccidioidomycosis

For each of the f ollowing diseases, name the fungus/yeast responsible and the drug of choice:

Rose gardener disease with ascending lymphangitis

Sporothrix schenckii—potassium iodide

Tinea nigra

Phaeoannellomyces werneckii—topical salicylic acid

Thrush in an immunocompromised patient

Candida albicans—nystatin (swish and swallow) and amphotericin B if systemic infection

San Joaquin (desert valley) fever; endemic to southwest United States, California

Coccidioides immitis—fluconazole and amphotericin B

Interstitial pneumonia of the immunocompromised

Pneumocystis carinii (or P. jiroveci)—TMP-sulfamethoxazole (SMX) or pentamidine (prophylaxis when CD4+200 cells/mL)

Tinea (pityriasis) versicolor

Malassezia furfur—topical miconazole or selenium sulfide

Meningitis from pigeon droppings

Cryptococcus neoformans—amphotericin + flucytosine for 2 weeks followed by fluconazole

Tinea cruris/capitis/corporis/unguium/pedis

Trichophyton, Epidermophyton, or Microsporum sp.—topical miconazole, oral griseofulvin for capitis and unguium

Fungus ball in lungs or invasive disease

Aspergillus fumigatus—voriconazole

ANTIFUNGALS

Name the drug whose mechanism of action is described below:

Blocks ergosterol (unique to fungi) synthesis by inhibiting P-450

Azole family (ketoconazole, fluconazole, miconazole, voriconazole, and posaconazole)

Binds ergosterol → produces membrane pores

Amphotericin B and nystatin

Blocks ergosterol synthesis by blocking squalene epoxidase

Terbinafine

Interferes with microtubule formation → inhibits mitosis

Griseofulvin

Converted to 5-fluorouracil (5-FU) → blocks formation of purines

Flucytosine

Name the antifungal drug(s) associated with each of the following unique toxicities:

Rigors, acute febrile reaction, nephrotoxicity, and arrythmias

Amphotericin B—follow BUN/creatinine daily. Note: newer lipid formulations (ie, AmBisome less nephrotoxic)

Photosensitivity, mental confusion, bone marrow suppression, and induces P-450

Griseofulvin

Antiandrogenic effects, adrenal suppression, and liver dysfunction

Azole family (especially ketoconazole)

Bone marrow suppression and alopecia

Flucytosine

PARASITOLOGY

Protozoa

Name the protozoan associated with each of the following statements:

Transmitted by Tsetse fly; shows antigenic variation

Trypanosoma brucei (gambiense and rhodesiense)

Transmitted by Anopheles mosquito

Plasmodium

Transmitted by Reduviid bug

Trypanosoma cruzi

Transmitted by cysts in meat or cat feces

Toxoplasma

Transmitted by sandfly

Leishmania

Obligate intracellular parasite; cysts on acid-fast stain

Cryptosporidium

Maltese “X” cross shape

Babesia

Pear-shaped, binucleate, flagellated trophozoite

Giardia lamblia

Blood smear shows trophozoites and schizonts

Plasmodium

Macrophages containing amastigotes

Leishmania donovani

For each of the following clinical findings, name the associated protozoan and the treatment:

Megacolon, megaesophagus, and cardiomegaly (with apical atrophy)

Trypanosoma cruzii (Chagas disease)—nifurtimox

Cyclic fever, headache, anemia, and splenomegaly

Plasmodium—chloroquine for erythrocyte forms and primaquine for latent forms (Plasmodium vivax and Plasmodium ovale)

Chloroquine-resistant malaria

Plasmodium falciparum—mefloquine or quinine and pyramethamine/sulfadoxine

Bloody diarrhea with “flask-shaped” ulcers, liver abscesses, and trophozoites in stool

Entamoeba histolytica—metronidazole and iodoquinol

Black fever or “kala-azar”

Leishmania donovani—sodium stibogluconate (pentavalent antimony)

Severe, watery diarrhea in AIDS patient

Cryptosporidium—supportive (hydration, improve immune status)

Flatulence, bloating, and foul-smelling diarrhea

Giardia lamblia—metronidazole

African sleeping sickness

Trypanosoma brucei (gambiense and rhodesiense)—suramin (acutely) or melarsoprol (for CNS symptoms)

Encephalitis with brain abscesses in immunocompromised host; congenital defects

Toxoplasma gondii—pyrimethamine and sulfadoxine or clindamycin

Vaginitis with foul-smelling, frothy discharge

Trichomonas vaginalis—metronidazole

Fever and hemolytic anemia after Ixodes tick bite

Babesia sp.—quinine and clindamycin

Why are many Africans resistant to P. vivax infection?

They carry sickle cell trait and/or they lack antigens Duffy a and b on RBCs.

What causes the cyclic symptoms in malaria?

Immune response to burst RBCs that release merozoites

Helminths

For each of the following clinical findings, name the associated helminth and the treatment:

Larvae penetrate skin of feet; GI infection → anemia

Ancylostoma duodenale or Necator amencanus (hookworms)—mebendazole or pyrantel pamoate

Worms visibly crawling in conjunctiva; spread by deerfly

Loa loa—diethylcarbamazine

Fever, periorbital edema, and myositis after ingesting raw pork

Trichinella spiralis—thiabendazole

River blindness; spread by female blackflies

Onchocerca volvulus—ivermectin (rIVERmectin for RIVER blindness)

Elephantiasis from lymphatic blockage

Wuchereria bancrofti—diethylcarbamazine

Larvae penetrate skin → autoinfection; GI infection

Strongyloides stercoralis—(threadworm)-thiabendazole or ivermectin

Intestinal infection and anal pruritis; ↑ incidence in children; positive “tape test”

Enterobius vermicularis (pinworms)—mebendazole or pyrantel pamoate

Fluke associated with squamous cell carcinoma of the urinary tract

Schistosoma haematobium—praziquantel

Granulomatous hepatitis and chorioretinitis

Toxocara canis—diethylcarbamazine

GI infection; competes for food → malnutrition in children; eggs visible in feces

Ascaris lumbricoides—mebendazole or pyrantel pamoate

Inflammation and 2° bacterial infection of lungs from undercooked crab meat

Paragonimus westermani—praziquantel

Biliary tract inflammation from undercooked fish

Opisthorchis (Clonorchis) sinensis—praziquantel

Undercooked pork larval worm → mass lesions in brain; cysticercosis

Taenia solium—praziquantel or niclosamide, albendazole for cysticercosis

Hydatid liver cysts from eggs in dog feces → anaphylaxis if antigens released from cysts

Echinococcus granulosus—albendazole, careful surgical removal of cysts (preinjected with ETOH)

Fish tapeworm causing vitamin B_12deficiency

Diphyllobothrium latum—praziquantel

Cercariae penetrate skin → granulomas and inflammation of liver and spleen; snails are hosts

Schistosoma sp.—praziquantel

Which cell count is elevated during many helminth infections and can be detected by routine CBC?

Eosinophils

Which is the most common helminth infection in the United States?

Enterobius vermicularis

Name the antiparasitic drug(s) associated with each of the following unique toxicities:

Cinchonism

Quinine

Hemolytic anemia in G6PD-deficient person

Chloroquine, primaquine, quinine, and TMP-SMX

Mazzotti reaction (pyrexia, hypotension, and respiratory distress caused by death of parasites)

Diethylcarbamazine (with Onchocerca)

CHAPTER 4

Neuroscience

EMBRYOLOGY

Name the structure(s) in the adult nervous system that arise from the following embryonic components:

Alar plate

Sensory neurons

Basal plate

Motor neurons

Telencephalon

Cerebral hemispheres and lateral ventricles

Diencephalon

Thalamus, optic nerves, and third ventricle

Mesencephalon

Midbrain and aqueduct

Metencephalon

Pons, cerebellum, and superior fourth ventricle

Myelencephalon

Medulla and inferior fourth ventricle

Neural crest cells

Peripheral sensory and autonomic nerves and sensory ganglia

What is the level of the conus medullaris in a newborn and in an adult?

L2 or L3 (newborn), L1 (adult)

NEUROANATOMY AND NEUROPHYSIOLOGY

Organization of the Nervous System

What are the divisions of the autonomic nervous system?

Sympathetic, parasympathetic

Where are the preganglionic cell bodies of the sympathetic nervous system?

Intermediolateral horn of the spinal cord from T1 to L3

Where are the preganglionic cell bodies of the parasympathetic nervous system located?

Brainstem (cranial nerve nuclei) and spinal cord from S2 to S4

Which is the primary neurotransmitter (NT) of both sympathetic and parasympathetic ganglia?

Acetylcholine (ACh)

Which is the primary type of cholinergic receptor of both sympathetic and parasympathetic ganglia?

Nicotinic

Which NT mediates the transmission of impulses from sympathetic neurons to effector organs?

Norepinephrine (NE)

Which NT mediates the transmission of impulses from parasympathetic neurons to effector organs?

ACh

Which NT mediates the transmission of impulses from somatic neurons to skeletal muscle?

ACh

What types of receptors are present on the effector organs innervated by the sympathetic nervous system?

α_1, α_2, β_1, and β_2

What type of receptor is present on the effector organs innervated by the parasympathetic nervous system?

Muscarinic

What type of receptor is present on muscle innervated by the somatic nervous system?

Nicotinic

Sympathetic Nervous System

Name the effect of the sympathetic nervous system on the f ollowing organ systems and the type of receptor which mediates each effect:

Eyes

Pupillary dilation (α1)

Salivary glands

Increased thick, viscous secretions

Bronchioles

Bronchodilation (β_2), ↑ secretions

Heart

Tachycardia (β_1), ↑ contractility (β_1), ↑ AV nodal conduction (β_1)

Vascular smooth muscle

Vasoconstriction of cutaneous mucous membrane and splanchnic vessels (α_1); vasodilation in skeletal muscle (β_2)

Gastrointestinal (GI) tract

↓ Muscle motility and tone (β_2), contraction of sphincters (α_1)

Male sex organs

Ejaculation (α_2)

Uterus

Relaxation (β_2), contraction (α_1)

Bladder and ureters

Relaxation of detrusor (β_2) contraction of trigone and sphincter (α1)

Sweat glands

↑ Secretions (muscarinic)

Kidneys

↑ Renin secretion

Adipocytes

↑ Lipolysis (β1)

Pancreas

↓ Insulin secretion (α_2), ↑ insulin secretion (β_2)

Parasympathetic Nervous System

What is the effect of the parasympathetic nervous system on the f ollowing organ systems:

Eyes

Pupillary constriction

Bronchioles

Bronchoconstriction

Heart

Bradycardia, ↓ contractility, ↓ AV nodal conduction

GI tract

↑ Motility, relaxation of sphincters

Male sex organs

Erection

Bladder and ureters

Contraction of detrusor, relaxation of sphincters and trigone

What type of cholinergic receptor mediates all of the effects on the organs above?

Muscarinic

Motor and Sensory Fibers?

What type of motor fiber innervates extrafusal muscle fibers?

A-alpha (A-α)

What type of motor fiber innervates intrafusal muscle fibers?

A-gamma (A-γ)

Name the function of each of the following types of sensory fibers:

Ia (A-α)

Proprioception, muscle spindles

Ib

Proprioception, Golgi tendon organs

II (A-β)

Touch, pressure, and vibration; secondary afferents of muscle spindles

III (A-δ)

Touch, pressure, fast pain, and temperature

IV (c)

Slow pain and temperature (unmyelinated)

What types of sensory fibers have the largest diameter and consequently the fastest conduction velocity?

Ia and Ib

What type of motor fibers have the largest diameter and consequently the fastest conduction velocity?

A-α

What type of sensory fibers have the smallest diameter and consequently the slowest conduction velocity?

C

What is the electrochemical effect of an inward Na+ current on a sensory fiber?

Depolarization

Name the function of each of the following components of a sensory pathway:

Sensory receptor

Translates environmental stimulus into an electrical impulse

First-order neuron

Carries impulse from sensory receptor into central nervous system (CNS)

Second-order neuron

Carries impulse from primary neuron to the thalamus

Third-order neuron

Carries impulse from second-order neuron to the cerebral cortex

Fourth-order neuron

Carries impulses from third-order neurons to appropriate somatosensory area of cerebral cortex

Name the type of mechanoreceptor described below:

Onion-like subcutaneous receptors that respond to vibration and tapping

Pacinian corpuscle

Primary receptors of the dermal papillae that mediate two-point tactile discrimination

Meissner corpuscle

Encapsulated receptor that responds to pressure

Ruffini corpuscle

Disc-shaped touch receptor of the deep dermis

Merkel tactile disc

Rods or cones?

Sensitive to low-intensity light

Rods

Sensitive to high-intensity light

Cones

Receptor used primarily for night vision

Rods

Receptor used primarily for day vision

Cones

Present in fovea

Cones

High visual acuity

Cones

Receptor which adjusts to low light conditions most rapidly

Cones

Receptor capable of color vision

Cones

Name the type of muscle sensor for each of the following functions:

Detection of static and dynamic changes in muscle length

Muscle spindles

Detection of muscle tension

Golgi tendon organs

Detection of vibration

Pacinian corpuscles

Detection of pain

Free nerve endings

What type of motoneuron is responsible for ensuring that a muscle will respond appropriately throughout contraction, despite changes in tension?

γ-Motoneurons

What type of muscle reflex, mediated by type Ia afferent fibers, causes muscle contraction in response to muscle stretch?

Stretch or myotatic reflex

What type of muscle reflex, mediated by type Ib afferent fibers, causes muscle relaxation in response to muscle contraction?

Golgi tendon reflex

What type of muscle reflex, mediated by types II, III, and IV afferent fibers, causes ipsilateral flexion and contralateral extension?

Flexor withdrawal reflex

What are the components of the afferent limb of a myotatic reflex arc?

Muscle spindle receptor → Ia fiber → dorsal root ganglion

What comprises the efferent limb of a myotatic reflex arc?

Ventral motor neuron

For each of the following muscle stretch reflexes, name the muscle group and spinal level tested:

Ankle jerk

Gastrocnemius (S1)

Knee jerk

Quadriceps (L2-L4)

Biceps jerk

Biceps (C5-C6)

Forearm jerk

Brachioradialis (C5-C6)

Triceps jerk

Triceps (C7-C8)

What type of posturing is caused by a transecting lesion above the level of the medulla but below the midbrain?

Decerebrate rigidity

What type of posturing is caused by a transecting lesion above the level of the red nucleus (midbrain)?

Decorticate rigidity

What are the three layers of the cerebellar cortex?

1. Granular layer (innermost)

2. Purkinje layer (middle)

3. Molecular layer (outermost)

Which is the major NT of cerebellar Purkinje cells?

γ-Aminobutyric acid (GABA).

Note: The output of Purkinje cells is always inhibitory.

Meninges

What are the three layers of the meninges?

“The meninges PAD the CNS”

1. P ia

2. A rachnoid

3. D ura

What meningeal space, which lies between the pia and arachnoid, contains the cerebrospinal fluid (CSF)?

Subarachnoid space

What structure produces CSF?

The choroid plexus of the lateral, third, and fourth ventricles

What structures reabsorb CSF into venous circulation?

The arachnoid granulations

Trace the flow of CSF from the choroid plexus into venous circulation.

Choroid plexus → lateral ventricles → interventricular foramina (of Monro) → third ventricle → cerebral aqueduct → fourth ventricle → lateral foramina (of Luschka) or median foramen (of Magendie) → subarachnoid space → arachnoid granulations → superior sagittal sinus

What are the three major functions of CSF?

1. To provide support and protection to the CNS

2. To remove metabolic waste products

3. To transport hormones and cytokines throughout the CSF and to the systemic circulation

Vasculature of the Central Nervous System

Name the blood vessel that supplies each of the following structures:

Anterior two-thirds of the spinal cord, the medullary pyramids, medial lemniscus, and root fibers of cranial nerve (CN) XII

Anterior spinal artery

Retina

Central artery of the retina (a branch of the ophthalmic artery)

Lateral geniculate body, globus pallidus, posterior limb of internal capsule

Anterior choroidal artery (an important branch of internal carotid artery)

Hypothalamus and ventral thalamus

Posterior communicating artery

Leg-foot area of motor and sensory cortices

Anterior cerebral artery (ACA)

Anterior putamen, caudate nucleus, and anteroinferior internal capsule

Medial striate arteries (branches of the ACA)

Broca (expressive) and Wernicke (receptive) speech areas, face and arm areas of motor cortices, frontal eye field

Middle cerebral artery (MCA)

Internal capsule, caudate nucleus, putamen, globus pallidus

Lateral striate arteries (branches of the MCA)

Nucleus ambiguus and the inferior surface of the cerebellum

Posterior inferior cerebellar artery

Caudal lateral pontine tegmentum (including portions of the nuclei of CN V, VII) and the inferior cerebellar surface

Anterior inferior cerebellar artery

Superior surface of cerebellum, cerebellar nuclei, and the cochlear nuclei

Superior cerebellar artery

Majority of midbrain, portions of the thalamus, lateral and medial geniculate bodies, occipital lobe, inferior aspect of the temporal lobes, and the hippocampus

Posterior cerebral artery (PCA)

Majority of the dura

Middle meningeal artery

Name the cerebral veins that drain directly into the superior sagittal sinus:

Bridging veins

Name the cerebral vein that drains deep cerebral veins into the straight sinus:

Vein of Galen

CN III, CN V_1, CN V_2, CN VI, postganglionic sympathetic fibers, and both internal carotid arteries all pass through which structure?

Cavernous sinus

Axonal Transport

Name the cytoplasmic structure in the nerve cell body and dendrites that are involved in protein synthesis:

Nissl substance

Name the type of axonal transport described below:

Transport responsible for delivery of synthesized NTs away from the cell body

Fast anterograde axonal transport

Transport responsible for delivery of cytoskeletal and cytoplasmic components away from the cell body

Slow anterograde transport

Transport responsible for returning material to the cell body for degradation

Fast retrograde transport

Kinesin-dependent transport

Fast anterograde axonal transport

Dynein-dependent transport

Fast retrograde transport

Transport responsible for carrying nerve growth factor, viruses, and toxins to cell bodies

Fast retrograde transport

Name the process of anterograde axonal and myelin degeneration accompanied by Schwann cell proliferation:

Wallerian degeneration

Supporting Cells of the Nervous System

Name the type of cell described below:

Primary supportive cell type of the CNS

Astrocyte

Myelin-producing cell type of the CNS

Oligodendrocyte

CNS scavenger cell type

Microglia

CSF-producing cell type

Ependymal cell

Myelin-producing cell type of the peripheral nervous system (PNS)

Schwann cells

What type of intercellular connections are responsible for maintaining the integrity of the blood-brain barrier?

Tight junctions

What proteins are commonly used to identify astrocytes?

Glial fibrillary acidic protein (GFAP) and glutamine synthetase

Pigments and Inclusions

Name the process or disease associated with the following neuronal histopathologic findings:

Lipofuscin granules

Aging

Depletion of neuromelanin in substantia nigra and Lewy bodies

Parkinson disease

Negri bodies

Rabies

Amyloid plaques and neurofibrillary tangles

Alzheimer disease

Cowdry type A inclusion bodies

Herpes simplex encephalitis

Spinal Tracts

Name the spinal tract responsible for each of the following functions:

Voluntary control of skeletal muscle

Lateral corticospinal/pyramidal tract

Sensation of pain and temperature

Lateral spinothalamic tract

Two-point discrimination and vibratory sensation

Dorsal column-medial lemniscus tract

Control of facial muscles

Corticobulbar tract

Coordination of muscle tone, posture, balance, and motor activity

Dentothalamic tract

Describe the major difference between the innervation of the lower and upper facial muscles.

Corticobulbar fibers innervate the lower facial muscles unilaterally, while upper facial muscles are innervated bilaterally

Name the structure in the spinal cord composed of ascending fibers of the dorsal column-medial lemniscus pathway originating in the upper extremities:

Cuneate fasciculus

Name the structure in the spinal cord composed of ascending fibers of the dorsal column-medial lemniscus pathway originating in the lower extremities:

Gracile fasciculus (medial to cuneate fasciculus)

At what level of the brainstem do fibers of the dorsal column-medial lemniscus pathway cross?

Caudal medulla

What type of receptors provide input to the lateral spinothalamic tract?

Free nerve endings

At what level do fibers of the spinothalamic tract cross?

At the same level or 1 to 2 levels above/below where they enter the spinal cord

Name the structure where fibers of the lateral spinothalamic tract cross the midline:

Ventral white commissure/anterior commisure

Where do fibers of the dorsal column-medial lemniscus pathway, the trigeminothalamic, and lateral spinothalamic tract all terminate?

The sensory cortex (Brodmann areas 3, 1, and 2)

What part of the cortex gives rise to the fibers of the lateral corticospinal and corticobulbar tracts?

The motor, premotor, and sensory areas of the cortex (Brodmann areas 6, 4, and 3, 1, 2)

Fibers of the lateral corticospinal tract pass through which limb of the internal capsule?

Posterior limb

Name the structure where fibers of the lateral corticospinal tract cross the midline:

Medullary pyramids

Classify each of the following clinical findings as upper motor neuron (UMN) or lower motor neuron (LMN) signs:

Spastic paresis

UMN

Flaccid paralysis

LMN

Babinski sign (upgoing toes)

UMN

Fasciculations and fibrillations

LMN

Areflexia

LMN

Atrophy

LMN

Hyperreflexia

UMN

Cranial Nerves

Name the cranial foramen that each of the cranial nerves below pass through:

I

Cribiform plate

II

Optic canal

III, IV, V_1, VI

Superior orbital fissure. Note: all of these nerves pass through the cavernous sinus as well.

V_2

Foramen Rotundum

V_3

Foramen Ovale (for divisions of the trigeminal nerve think “S tanding R oom O nly”)

VII, VIII

Internal acoustic meatus

IX, X, XI

Jugular foramen

XII

Hypoglossal canal

Name the function(s) for each cranial nerve listed below:

I: olfactory

Smell

II: optic

Vision

III: oculomotor

1. Eye movement

2. “Parasympathetic” ciliary and pupillary sphincter mm

Note: mm is used as the abbreviation for “muscles”.

IV: trochlear

Contraction of superior oblique muscle

V_1: trigeminal—ophthalmic branch

Sensation from nose to forehead

V_2: trigeminal—maxillary branch

Sensation from lateral nose, upper lip, superior buccal area

V_3: trigeminal—mandibular branch

1. Sensation from areas of the lower face not covered by V_1 and V_2

2. Movement of the Muscles of Mastication (Masseter, teMporalis, Medial, and lateral pterygoids), tensor veli palatini, and tensor tympani

VI: abducens

Contraction of lateral rectus muscle

VII: facial

1. Parasympathetic—lacrimal, submandibular, and sublingual glands

2. Mm of facial expression, stapedius, stylohyoid, and the posterior belly of the digastric muscle

3. Taste—anterior two-thirds of tongue

4. Sensation—skin of external ear

VIII: vestibulocochlear

Hearing and sense of balance

IX: glossopharyngeal

1. Parasympathetic—parotid gland

2. Motor—stylopharyngeus mm

3. Taste—posterior one-third tongue

4. Sensation—parotid gland, carotid body and sinus, pharynx, and middle ear

5. Cutaneous sensation—external ear canal

X: vagus

1. Parasympathetic—trachea, bronchi, heart, GI tract

2. Contraction of laryngeal, pharyngeal, and esophageal striated mm

3. Taste—epiglottis and palate

4. Sensation—trachea, GI tract

5. Cutaneous sensation—external ear

XI: accessory

Movement of sternocleidomastoid and trapezius muscles

XII: hypoglossal

Contraction of muscles of tongue

Which three cranial nerves are purely sensory nerves?

1. CN I

2. CN II

3. CN VIII

Which five cranial nerves are purely motor nerves?

1. CNIII

2. CNIV

3. CNVI

4. CNXI

5. CNXII

Which four cranial nerves have both motor and sensory components?

1. CNV

2. CNVII

3. CNIX

4. CNX

Which two cranial nerves are rostral to the midbrain?

1. CNI

2. CNII

Which two cranial nerve nuclei are located in the midbrain?

1. CNIII

2. CNIV

Which four cranial nerves have at least a portion of their nuclei in the pons?

1. CNV

2. CNVI

3. CNVII

4. CNVIII

Which seven cranial nerves have at least a portion of their nuclei in the medulla?

1. CN V

2. CN VI

3. CN VII

4. CNVIII

5. CN IX

6. CNX

7. CNXII

Name the only cranial nerve that crosses the midline and exits the brainstem posterior to the ventricular system:

CN IV—exits the brainstem posteriorly and crosses the midline after exiting the caudal midbrain

What nucleus serves as the origin of preganglionic parasympathetic fibers projecting to the ciliary ganglion?

Edinger-Westphal nucleus of CN III

What visceral sensory nucleus, located in the medulla, is a relay center for taste, sensory input from the carotid sinus, carotid body, and the vagus nerve?

Nucleus Solitarius

What visceral motor nucleus, located in the medulla, is involved in coordinating swallowing and speech?

Nucleus aMbiguus

Which are the afferent and efferent limbs of the corneal reflex?

CN V_1 and CN VII

Which are the afferent and efferent limbs of the pupillary light reflex?

CN II and CN III

Which are the afferent and efferent limbs of the gag reflex?

CN IX and CN X

Name the site of a lesion, within the visual tract, capable of causing each of the following deficits:

Ipsilateral blindness

Transection of the optic nerve

Binasal hemianopia

Bilateral lateral compression of optic chiasm

Bitemporal hemianopia

Midsagittal transection or midline pressure on the optic chiasm (often caused by a pituitary tumor)

Right hemianopia without macular sparing

Transection of the left optic radiation

Right upper quadrantanopia

Transection of the lower division of the left optic radiation

Right lower quadrantanopia

Transection of the upper division of the left optic radiation

Right hemianopia with macular sparing

Destruction of the left visual cortex

What are five key structures of the pupillary light reflex pathway?

1. Ganglion cells of the retina

2. Pretectal nucleus of the midbrain

3. Edinger-Westphal nucleus

4. Ciliary ganglion

5. Postganglionic parasympathetic fibers of CN III

What are four key structures of the pupillary dilation pathway?

1. Paraventricular nucleus of the hypothalamus

2. Ciliospinal center of Budge at the level of T1 to T2

3. Superior cervical ganglion

4. Postganglionic sympathetic fibers traveling along the internal carotid artery and its branches to the eye

What part of the cortex is responsible for voluntary eye movements?

Frontal eye field (Brodmann area 8)

What side will a patient’s eyes deviate toward if there is a lesion of the right frontal eye field?

Right side (“Look toward the lesion of frontal eye fields”)

What structure connects the nucleus of CN VI and the nucleus of CN III?

Medial longitudinal fasciculus (MLF)

What type of lesion will result in medial rectus palsy (inability to adduct the eye) on attempted lateral gaze but normal adduction on accommodation?

Intranuclear ophthalmoplegia (a lesion of the MLF)

What classic idiopathic lesion is characterized by ptosis, miosis, and anhydrosis?

Horner syndrome

Name the condition characterized by a pupil that will accommodate but cannot react to light:

Argyll-Robertson pupil (associated with tertiary syphilis, lupus, and diabetes mellitus)

Name the condition caused by a lesion in the afferent fibers of the light reflex pathway:

Marcus Gunn pupil

What are the primary sensory receptors of the auditory pathway?

Inner hair cells of the organ of Corti

Where does the auditory pathway terminate?

Bilateral input from both auditory tracts terminates in primary auditory cortex in superior temporal gyrus (Brodmann areas 41 and 42)

What type of cells are responsible for relaying auditory stimuli from the organ of Corti to the cochlear nuclei?

Bipolar cells of the spiral or cochlearganglion

What thalamic nucleus plays a key role in relay of impulses from the cochlear nuclei to higher cortical centers?

Medial geniculate body of the thalamus

What pontine nucleus plays a key role in sound localization?

Superior olivary nucleus

What are key structures of the hearing pathway?

Cochlear → cochlear nucleus → decussating fibers in Trapezoid body → superior olivary nucleus → lateral lemniscus → inferior colliculi → medial geniculate nucleus → primary auditory cortex

Conduction deafness is caused by a lesion of which components of the auditory system?

External auditory canal, tympanic membrane, or the middle ear

Sensorineural deafness is caused by a lesion of which components of the auditory system?

Cochlea, cochlear nerve, or the cochlear nuclei

Patients with presbycusis have trouble hearing what types of sounds?

High-frequency sounds

Which cells of the vestibular system respond to angular acceleration and deceleration?

The hair cells of the three semicircular canals

What structures of the vestibular system respond to linear acceleration and deceleration?

The hair cells of the utricle

What type of cells are responsible for relaying vestibular stimuli from the hair cells to the vestibular nuclei?

Bipolar cells of the vestibular ganglion

What structures provide input to the vestibular nuclei?

Hair cells of the semicircular canal, hair cells of the utricle, and the flocculonodular lobe of the cerebellum

What structures receive signals from the vestibular nuclei?

The thalamus, spinal cord, cerebellum, and CNs III, IV, and VI

Cerebellum, Thalamus, Hypothalamus

What are the three primary functions of the cerebellum?

1. Maintenance of posture and equilibrium

2. Control of muscle tone

3. Coordination of voluntary muscle activity

What type of tremor may result from a cerebellar lesion?

Intention tremor

A positive Romberg sign (loss of balance when the eyes are closed) suggests a lesion to which tract of the CNS?

Dentothalamic tract (the main cerebellar pathway) or dorsal column (tabes dorsalis in neurosyphilis)

Name the thalamic nucleus/nuclei responsible for the relay of impulses for each modality listed below:

Vision

Lateral geniculate nucleus (“Lateral to Look”)

Hearing

Medial geniculate nucleus (“Medial for Music”)

Proprioception, pain, pressure, touch, vibration

Lateral portion of ventral posteriornucleus (VPL, “Posterior for Proprioception, Pain”)

Facial sensation

Medial portion of ventral posterior nucleus (VML)

Motor

Ventral anterior/lateral nuclei

Limbic function

Dorsomedial, anterior nuclei

Name the largest thalamic nucleus:

Pulvinar

What is the function of the pulvinar?

Integration of visual, auditory, and somesthetic input

Which portion of the internal capsule contains fibers of the corticobulbar tract?

The genu

Which portion of the internal capsule contains fibers of the corticospinal, spinothalamic, visual, and auditory tracts?

The posterior limb

Which arteries supply the posterior limb of the internal capsule?

Perforating branches of the anteriorchoroidal artery and lenticulostriate arteries

Name the major hypothalamic nucleus (or nuclei) responsible for each function listed below:

Regulation of the release of gonadotropic hormones

Medial preoptic nucleus (which contains the sexually dimorphic nucleus)

Regulation of circadian rhythms

Suprachiasmatic nucleus

Regulation of body temperature

Anterior nucleus (lesion results in hyperthermia) and posterior nucleus (lesion results in poikilothermia)

Regulation of water balance, synthesis of antidiuretic hormone, oxytocin, and corticotropin-releasing factor

Paraventricular and supraoptic nuclei

Regulation of appetite

VentroMedial nucleus (lesion resulting from eating Very Much [hyperphagia, obesity]) and lateral hypothalamic nucleus (lesions cause anorexia and starvation)

Regulation of hypothalamus

Arcuate or infundibular nucleus

Regulation of emotional expression

Mammillary nucleus (a component of the limbic system)

What are the major structures of the Papez circuit?

Septal area, mammillary body, anteriornucleus of thalamus, cingulate gyrus, entorhinal cortex, and hippocampal formation

What is the most epileptogenic part of the cerebrum?

The hippocampus

What system within the CNS plays a central role in the initiation and coordination of somatic motor activity?

The striatal or extrapyramidal motor system

What are the major components of the striatal motor system?

Neocortex, basal ganglia (striatum [caudate + putamen], globus pallidus, subthalamic nucleus, substantia nigra), and thalamus

Neurotransmitters

Name the NT described below:

Major NT of the PNS

ACh

NT which is increased in the CNS of patients with schizophrenia

Dopamine

Major NT of the parasympathetic nervous system

ACh

NT believed to cause panic attacks when released suddenly by the locus coeruleus

NE

Major NT of the preganglionic sympathetic nervous system

ACh

NT highly concentrated in the substantia nigra that plays a key role in pain transmission

Substance P

Major NT of the postganglionic sympathetic neurons supplying sweat glands and certain blood vessels

ACh

NT which is depleted from the basal nucleus of Meynert in Alzheimer disease

ACh

NT which is depleted from the substantia nigra in patients with Parkinson disease

Dopamine

NT that causes renal vasodilation

Dopamine

Two NTs believed to be depleted in depression

1. NE

2. Serotonin

Powerful analgesic NT found exclusively in the hypothalamus

β-Endorphin

Opiate peptides which play a role in pain suppression

Enkephalins

NT that regulates release of GH and TSH; markedly ↓ Alzheimer disease

Somatostatin

Major inhibitory NT of the cortex

GABA

Major inhibitory NT of the spinal cord

Glycine

Major excitatory NT of the brain

Glutamate

Gaseous, vasoactive NT involved in memory

Nitrous oxide

NT important in the initiation of sleep

Melatonin

NT which inhibits the reticular activating center, thereby increasing total sleep time

ACh

Which two amino acids can serve as a precursor for the synthesis of catecholamines?

1. Phenylalanine

2. Tyrosine

Cerebral Cortex

What are the six layers of neocortex?

1. Layer I: molecular layer

2. Layer II: external granular layer

3. Layer III: external pyramidal layer

4. Layer IV: internal granular layer

5. Layer V: internal pyramidal layer

6. Layer VI: multiform layer

Name the site of a lesion, within the cortex, capable of causing each of the following deficits:

Right-sided flaccid hemiparalysis

Left primary motor area (Brodmann area 4)

Left-sided pronator drift

Right primary motor area (Brodmann area 4)

Loss of abstract thought and self-restraint

Bilateral loss of frontal lobes anterior to the frontal eye fields

Slowed speech without any impairment of language comprehension

Broca speech area (Brodmann areas 44, 45; always in the dominant hemisphere, usually left)

Loss of right-sided tactile sensation and proprioception

Left somesthetic area (Brodmann areas 3, 1, 2)

Cortical deafness

Bilateral destruction of the auditory areas (Brodmann areas 41, 42); unilateral destruction of the auditory area causes a slight ↓ in hearing.

Inability to understand spoken language and verbalize coherent thoughts

Wernicke speech area (Brodmann area 22) in the dominant hemisphere, usually left

Ipsilateral anosmia (inability to smell)

Primary olfactory area (Brodmann area 34)

Alexia and agraphia (inability to read and write)

Angular gyrus (Brodmann area 39)

Loss of ability to transfer information from short-term to long-term memory

Bilateral destruction of the hippocampal cortex

Psychic blindness, hyperphagia, docility, and hypersexuality (Klüver-Bucy syndrome)

Bilateral destruction of the anterior temporal lobes (amygdala)

Loss of ability to recognize faces

Inferomedial right occipitotemporal area

Loss of vision in the right visual field with macular sparing

Destruction of the left primary visual area (Brodmann area 17)

Name the term used to describe a deficit in the ability to draw a geometric figure:

Construction apraxia

Name the term used to describe a “magnetic gait,” commonly seen in normal-pressure hydrocephalus:

Gait apraxia

What part of the nervous system is involved in maintaining wakefulness?

Reticular activating system and bilateral cortex

PATHOLOGY OF THE NERVOUS SYSTEM

Congenital Disorders

Name the type of neural tube defect with the following features:

Failure of posterior vertebral arch closure (not evident on clinical examination)

Spina bifida occulta

Failure of posterior vertebral arch closure accompanied by herniation of the meninges

Spina bifida cystica

Herniation of the meninges outside of the spinal canal

Meningocele

Herniation of nervous tissue and meninges outside of the spinal canal

Myelomeningocele

Complete cerebral agenesis due to lack of closure of the anterior neuropore

Anencephaly

Diverticulum of malformed CNS tissue

Encephalocele

What factor is used to screen pregnant mothers for neural tube defects?

α-Fetoprotein

What is the most common cause of mental retardation?

Fetal alcohol syndrome, often associated with cardiac and facial anomalies

What are two common chromosomal genetic causes of mental retardation?

1. Trisomy 21

2. Fragile X

Name the condition characterized by an excess of CSF in the cranial cavity:

Hydrocephalus

What type of hydrocephalus is characterized by obstruction in the flow of CSF through the ventricular system and subarachnoid space?

Noncommunicating hydrocephalus

What type of hydrocephalus is characterized by free flow of CSF but abnormal CSF absorption?

Communicating hydrocephalus

What congenital malformation of the CNS is characterized by herniation of the cerebellar tonsils and medulla through the foramen magnum (which may result in obstruction of CSF circulation)?

Arnold-Chiari malformation (type 1)

What congenital malformation of the CNS is associated with syringomyelia (central cavitation of the spinal cord)?

Arnold-Chiari malformation (type 2)

What congenital malformation of the CNS is characterized by cystic dilation of fourth ventricle, agenesis of vermis, and associated with hydrocephalus?

Dandy-Walker malformation

What complication of premature babies usually results in hypoxic/ischemic injuries of brain?

Subependymal germinal matrix bleed

Stroke

Describe the artery that has been occluded in each of the following stroke syndromes:

Paresis and sensory loss of contralateral lower extremity

ACA

Hemiparesis, contralateral hemisensory loss, homonymous hemianopsia, aphasia

MCA supplying the dominant hemisphere, usually left hemisphere

Loss of consciousness, hemisensory loss, homonymous hemianopsia with macular sparing

PCA

Amaurosis fugax

Ophthalmic artery

Vertigo, cranial nerve palsies, impaired level of consciousness, dysarthria

Vertebrobasilar artery

Sensory neglect and apraxia

MCA supplying the nondominant hemisphere, usually right hemisphere

Urinary incontinence, suck and grasp reflexes

Middle or ACA supplying the frontal lobe

Ipsilateral loss of pain and temperature for face, contralateral pain and temperature for body

PICA—Wallenberg syndrome (lateral medulla)

What are the most frequent sites of thrombotic occlusion in the cerebral vasculature?

Carotid bifurcation, MCA, and basilar artery

What is the most frequent site of embolic occlusion in the cerebral vasculature?

MCA

Which cardiac arrhythmia is associated with embolic stroke?

Atrial fibrillation

What type of stroke, associated with HTN, causes the formation of small, cystic, moon-shaped pits?

Lacunar infarctions

Where do lacunar strokes usually occur?

Basal ganglia, thalamus, internal capsule, white matter, pons, cerebellum

Name the term used to describe small aneurysms of the cerebral vasculature, caused by long-standing HTN, that may result in intracerebral hemorrhage:

Charcot-Bouchard aneurysms

What are the most common locations for Charcot-Bouchard aneurysms?

Thalamus and basal ganglia

Within the cerebral vasculature, what are the most common sites of berry aneurysm formation?

At the bifurcations of the circle of Willis

What is the most common complication of berry aneurysms?

Rupture causing subarachnoid hemorrhage

What are three disorders that predispose to the formation of berry aneurysms?

1. Polycystic kidney disease

2. Ehlers-Danlos syndrome

3. Marfan syndrome

Which cranial nerve palsy is associated with internal carotid or posterior communicating artery aneurysms?

CN III palsy causing papillary dilation

Name the term used to describe paroxysmal, self-limiting episodes of neurologic deficit, commonly including transient aphasia.

Transient ischemic attack

Which syndrome is characterized by loss of all motor function except that of CN III and IV?

Locked-in syndrome (usually a result of infarction or tumor at the base of the pons)

Seizures

Name the type of seizure associated with the following clinical findings:

Loss of consciousness followed by loss of postural control, a tonic phase of muscle contraction and clonic limb jerking

Tonic-clonic seizure

A child who appears to be daydreaming in class and is found to have a 3-second spike-and-wave pattern on EEG

Absence seizure

Sudden, brief muscle contractions

Myoclonic epilepsy

Motor, sensory, visual, psychic, or autonomic phenomena with preserved level of consciousness

Simple partial seizure

Seizure begins with behavioral arrest, which is followed by auditory or visual hallucination, automatisms, and finally by postictal confusion

Complex partial seizure

What disorder is characterized by paroxysmal episodes of sharp, shooting facial pain in the distribution of one or more branches of CN V?

Trigeminal neuralgia

What is the drug of choice for trigeminal neuralgia?

Carbamazepine

What is the triad of cerebellar dysfunction?

1. Loss of balance (disequilibrium)

2. Hypotonia

3. Loss of coordinated muscle activity (dyssynergia)

Name the terms used to describe traumatic injury to the cortex at the site of impact and opposite the side of impact:

Coup injury (at the site of impact); contrecoup injury (opposite the site of impact)

Intracranial Hemorrhage

Name the type of intracranial hemorrhage associated with the following features:

Bloody or xanthrochromic CSF on lumbar puncture

Subarachnoid hemorrhage

Hematoma following the contour of a cerebral hemisphere on computed tomography (CT) scan

Subdural hematoma

Laceration of bridging cerebral veins

Subdural hematoma

Laceration of middle meningeal artery due to fracture of the temporal bone

Epidural hematoma

Lucid interval followed by rapid decline in mental status

Epidural hematoma

Most common type of intracranial hemorrhage resulting from trauma

Subdural hematoma

Ruptured berry aneurysm or arteriovenous malformation

Subarachnoid hemorrhage

Seen in patients with long-standing, poorly controlled HTN

Intraparenchymal hemorrhage

Lens-shaped hematoma on CT scan

Epidural hematoma

Crescentic hematoma on CT scan

Subdural hematoma

Seen more commonly in alcoholics and the elderly

Subdural hematoma

What is the most common cause of subarachnoid hemorrhage?

Trauma

Meningitis/Encephalitis

Name the type of meningitis associated with the following CSF findings:

Greater than 1000 polymorphonuclear mononuclear leukocytes, ↓ glucose, increased protein

Bacterial meningitis

Increased lymphocytes, minor elevation in protein, normal CSF pressure

Viral meningitis

Increased lymphocytes, minor elevation in protein, elevated CSF pressure

Fungal meningitis

Perivascular cuffing, inclusion bodies, and glial nodules may be seen in what cerebral infection?

Viral meningoencephalitis

Name the three most common bacteria1. causing neonatal meningitis:

1. Group B Streptococcus

2. Escherichia coli

3. Listeria

Name the parasite spread from cats to humans that causes periventricular calcifications and congenital disorders in offspring of infected mothers:

Toxoplasma gondii

Name the fungal meningitis most commonly associated with diabetics in DKA:

Mucormycosis

Bullet-shaped intracytoplasmic inclusions, Negri bodies are characteristic of which CNS viral infection?

Rabies

Hemorrhagic necrosis of temporal lobes is most commonly associated with which viral encephalitis?

HSV-1

Which infectious disease is characterized by neuronal vacuolization leading to small cysts in the gray matter of the brain without an associated inflammatory response?

Spongiform encephalopathy

Which disease is characterized by progressive ataxia, dementia, and spongiform gray matter changes?

Creutzfeldt-Jacob disease

Demyelinating Disorders

Name the demyelinating disorder associated with the following clinical and pathologic features:

Most common demyelinating disorder

Multiple sclerosis

Associated with JC virus infection in AIDS patients

Progressive multifocal leukoencephalopathy

Periventricular calcification; spinal Multiple sclerosis lesions typically in the white matter of the cervical cord

Multiple sclerosis

Postviral autoimmune syndrome causing demyelination of peripheral nerves, especially motor fibers

Guillain-Barré syndrome

Triad of intention tremor, scanning speech, and nystagmus

Multiple sclerosis

May present with intranuclear ophthalmoplegia (MLF syndrome) or sudden visual loss due to optic neuritis

Multiple sclerosis

Ascending paralysis, facial diplegia, and autonomic dysfunction

Guillain-Barré syndrome

Oligoclonal bands in the CSF

Multiple sclerosis

Albuminocytologic dissociation (↑ CSF protein with normal cell count)

Guillain-Barré syndrome

↑ CSF protein, normal glucose, ↑ lymphocytes

Multiple sclerosis

Leukodystrophies and Neurocutaneous Syndromes

Name the type of leukodystrophy associated with the following features:

Globoid bodies in white matter

Krabbe disease

Deficiency of β-galactocerebrosidase

Krabbe disease

Deficiency of arylsulfatase A

Metachromatic leukodystrophy

Nervous tissue demonstrates loss of myelin and appears yellowish brown, build up of cerebroside in myelin sheath

Metachromatic leukodystrophy

Peroxisomal deficiency, demyelination starts in occipital lobe and moves anteriorly

Adrenoleukodystrophy (X-linked)

Name the type of neurocutaneous syndromes associated with the following features:

Cutaneous and plexiform neurofibromas, Lisch nodules on iris, cafe au lait spots, axillary freckling

Neurofibromatosis (NF1)

Bilateral schwanomas, meningioma, ependyoma

NF2

Capillary hemagiomas, hemagioblastomas in cerebellum and retina, increased incidence of renal cell carcinoma

von Hippel-Lindau

Nasolabial subcutaneous angiofibroma, epilepsy, subependymal nodules, ungual fibroma, shagreen patch, ash leaf spots

Tuberous sclerosis

What is the inheritance pattern of neurocutaneous syndromes?

Autosomal dominant (AD)

What is the inheritance pattern of leukodystrophies?

Autosomal recessive (AR)

Neurodegenerative Disorders

What are the two most common causes of dementia in the elderly?

Alzheimer dementia and multi-infarct dementia

Name the neurodegenerative disorder associated with the following clinical and pathologic features:

Hirano bodies, neurofibrillary tangles, senile plaques (accumulations of β-amyloid protein)

Alzheimer dementia

Stepwise dementia in a patient with focal neurologic deficits

Multi-infarct dementia

Thiamine deficiency from alcohol abuse causing ophthalmoplegia, ataxia, nystagmus

Wernicke encephalopathy

Long-term alcohol abuse causing retrograde and anterograde amnesia, confabulation, and shrunken, petechial hemorrhage in mammillary bodies

Korsakoff psychosis

Progressive dementia with predominantly frontal and temporal gliosis and neuronal loss

Pick disease

Degeneration of the caudate nucleus

Huntington disease

Lewy bodies and depigmentation of the substantia nigra

Parkinson disease

Parkinsonian symptoms with autonomic dysfunction, including orthostatic hypotension

Shy-Drager syndrome

Resting tremor, cogwheel rigidity, akinesia, postural instability

Parkinson disease

Can be caused by MPTP use

Parkinson disease

Slowly progressive ataxia, dysarthria associated with kyphoscoliosis, diabetes, arrythmias, and myocarditis due to triplet repeat GAA on chromosome 9

Friedreich ataxia

Autosomal dominant (AD) inheritance and anticipation (worsening of disease in future generations) due to increasing number of CAG repeats on chromosome 4

Huntington disease

UMN and LMN signs due to loss of myelinated fibers of the corticospinal tract

Amyotrophic lateral sclerosis (ALS)

Viral infection → inflammatory response in anterior horn of the spinal cord → LMN loss

Poliomyelitis

Childhood ataxia associated with telangiectasias of the skin and conjunctiva associated with ATM gene mutation

Ataxia-telangiectasia

Floppy baby (hypotonia) due to LMN degeneration, tongue fasciculation

Werdnig-Hoffman disease

Which protein gives rise to the amyloid fibrils of Alzheimer disease?

A-β

Which is the conformation of A-β protein in neuritic plaques?

β-Pleated sheet

The A-β protein is derived from processing of which larger molecule?

Amyloid precursor protein (APP)

Brain Tumors

Where are the majority of adults versus children CNS tumors found?

Supratentorial for adults, infratentorial for children

Name the brain tumor associated with each of the following clinical or pathologic findings:

Most common pediatric intracranial tumor

Juvenile pilocytic astrocytoma

Most common pituitary tumor

Pituitary adenoma

Most common pituitary adenoma

Prolactinoma

Most common pediatric supratentorial tumor

Craniopharyngioma

Most common primary brain tumor

Glioblastoma multiforme

Most common intracranial tumor

Metastases

Malignant pediatric tumor which metastases through CSF pathways

Medulloblastoma

Malignant pediatric tumor found exclusively in the posterior fossa

Medulloblastoma

Vascular tumor of cerebellum and retina in patients with von Hippel-Lindau syndrome

Hemangioblastoma

Abundant capillaries and vacuolated foam cells

Hemangioblastoma

Type of tumor that is found bilaterally in patients with neurofibromatosis II

Vestibular schwannoma

Tumor of the dorsal root that may grow in a dumbbell configuration through a vertebral foramen

Schwannoma

Tumor which originates from the vestibular division of CN VIII

Schwannoma

Tumor which grows in a mixture of Antoni A or Antoni B patterns

Schwannoma

Small round blue cell tumor

Medulloblastoma

Bipolar cells, Rosenthal fibers, and microcysts

Juvenile pilocytic astrocytoma

Verocay bodies

Schwannoma

Tumor derived from Rathke pouch

Craniopharyngioma

Two tumors often presenting with bitemporal hemianopia

Pituitary adenoma and craniopharyngioma

Tumor characterized by concentric whorls and calcified psammoma bodies

Meningioma

Tumor arising from ependymal lining of ventricular system

Ependymoma

Tumor commonly arising in the pineal region causing obstructive hydrocephalus by compromising the aqueduct of Sylvius

Germinoma

EBV positive B-cell tumor of the CNS in AIDS patients

CNS lymphoma

Tumor of the foramen of Monro causing obstructive hydrocephalus

Colloid cyst of the third ventricle

Benign tumor characterized by calcifications and cells with fried-egg appearance or perinuclear halos

Oligodendroma

Tumor characterized by highly malignant cells bordering necrotic areas

Glioblastoma multiforme

Benign tumor derived from arachnoid cap cells with well-delineated margins

Meningioma

Disorders of the Spinal Cord

Name a disease of the spinal cord associated with each of the following neurologic findings:

Loss of all spinal modalities except tactile discrimination, vibratory sensation, and proprioception

Ventral spinal artery occlusion

Impaired tactile discrimination, vibratory sensation, and proprioception

Tabes dorsalis

Loss of pain and temperature sensation in a cape-like distribution and flaccid paralysis of the intrinsic muscles of the hand

Syringomyelia

Impaired tactile discrimination, vibratory sensation and proprioception, UMN signs, and ataxia

Vitamin B_12 deficiency

Miscellaneous

What complication affecting the brainstem can be caused by rapid correction of hyponatremia?

Central pontine myelinolysis

Describe how transtentorial herniation causes contralateral hemiparesis.

Compresses the right crus cerebri → corticospinal and corticobulbar fibers are compromised (Kernohan notch)

Describe how transtentorial herniation causes pupillary dilation.

Tension on CN III causes pupillary dilation.

Name a life-threatening complication of transforaminal or tonsillar herniation:

Compression of the medullary respiratory center → respiratory insufficiency

What is the term used to describe brainstem hemorrhages caused by transtentorial and transforaminal herniation?

Duret hemorrhages

What is the systemic response to increased intracranial pressure (Cushing triad)?

1. HTN

2. Bradycardia

3. Irregular respirations

What is the most common reversible cause of dementia in the elderly?

Normal pressure hydrocephalus

Normal pressure hydrocephalus is a common complication of what type of intracranial pathology?

Subarachnoid hemorrhage

What is the triad of normal-pressure hydrocephalus?

1. Ataxic, magnetic gait (Wobbly)

2. Dementia and/or short-term memory loss (Weird)

3. Urinary incontinence (Wet)

What diuretic is commonly used to manage increased intracranial pressure?

Mannitol (provides osmotic diuresis)

What is the protein change associated with prion diseases?

Conformational change in PrPc (α-helix isoform) to PrPsc (β-pleated sheet isoform)

PHARMACOLOGY OF THE NERVOUS SYSTEM

Antiepileptics

For each of the following drugs, name:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects or important toxicity (TOX) (if any)

Carbamazepine

MOA: Na+ channel blocker

IND: Tonic-clonic, partial, and Jacksonian seizures

TOX: ↑ LFT, agranulocytosis, a plastic anemia

Ethosuximide

MOA: May block T-type Ca2+ channels in thalamus

IND: Absence seizures

TOX: GI upset, Stevens-Johnson syndrome

Diazepam

MOA: Facilitates GABA action by ↑ frequency of Cl channel opening

IND: Status epilepticus

TOX: Sedation

Lamotrigine

MOA: Blocks Na+ channels

IND: Adjuvant antiepileptic agent

TOX: Life-threatening rash and Stevens-Johnson syndrome

Phenytoin

MOA: Na+ channel blocker

IND: Tonic-clonic, partial, and status

TOX: Nystagmus, ataxia, gingivalhyperplasia, hirsutism, megalobasticanemia, teratogenic

Phenobarbital

MOA: Facilitates GABA action by ↑ duration of Cl channel opening

IND: Tonic-clonic seizures

TOX: Induces P-450, drowsiness

Valproic acid

MOA: Unknown—may facilitate GABA action

IND: Myoclonic seizures

TOX: Hepatotoxicity, GI toxicity, inhibits P-450, thrombocytopenia

Name the drug(s) of choice for each of the following types of epilepsy:

Simple and complex partial

Phenytoin, carbamazepine

Absence

Ethosuximide

Febrile

Phenobarbital

Myoclonic

Valproic acid, clonazepam

Status epilepticus

Phenytoin, diazepam

Tonic-clonic

Phenytoin, carbamazepine

Antiparkinsonian Agents

For each of the following drugs, name:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects or important toxicity (TOX) (if any)

Amantidine

MOA: May enhance dopamine release

IND: Helpful for rigidity and bradykinesia

TOX: Acute psychosis (rare)

Benztropine

MOA: Antimuscarinic

IND: Adjuvant therapy

TOX: Similar to atropine

Bromocriptine

MOA: Dopamine receptor agonist

IND: Used with levodopa

TOX: Hypotension, confusion, hallucinations, nausea

Levodopa

MOA: Dopamine precursor converted to dopamine in CNS

IND: Combined with carbidopa, levodopa is the most efficacious regimen for Parkinson disease

TOX: Nausea, tachycardia, hypotension, hallucinations, dyskinesias

Carbidopa

MOA: Inhibition of dopamine decarboxylase →↑ levodopa availability in CNS

IND: Used with levodopa

TOX: spasms of the eyelid, irregular heartbeat, confusion, agitation, hallucinations

Selegiline

MOA: Inhibition of MAOb →↑ dopamine levels in CNS

IND: Used as adjuvant to levodopa

TOX: HTN

Anesthetics

For each of the following drugs, provide:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects or important toxicity (TOX) (if any)

Halothane

MOA: CNS depression

IND: Prototype general anesthetic; potent anesthetic but weak analgesic

TOX: Arrhythmias, ↓ cardiac output, hypotension, hepatotoxicity

Nitrous oxide

MOA: CNS depression

IND: Weak general anesthetic, strong analgesic

TOX: Anoxia, vitamin B_12 deficiency (with chronic use)

Thiopental

MOA: Prolongs inhibitory postsynaptic potentials by ↑ GABA levels (similar to phenobarbital)

IND: Surgical anesthesia

TOX: Laryngospasm

Benzodiazepines (diazepam, midazolam)

MOA: Facilitates GABA action by ↑ frequency of Cl- channel opening

IND: Sedative, hypnotic, anxiolytic

TOX: Sedation

Ketamine

MOA: PCP analog

IND: General anesthetic

TOX: Postoperative hallucinations, amnesia, respiratory depression

Propofol

MOA: CNS depression

IND: General anesthetic—rapid onset and clearance

TOX: Cannot be given to patients with egg or soybean allergies

Local anesthetics (procaine, cocaine, tetracaine, lidocaine, bupivacaine)

MOA: Block Na+ channels

IND: Anesthetic for minor procedures, spinal blocks

TOX: Arrhythmias, HTN; cardiotoxicity (bupivacaine), seizures

Succinylcholine

MOA: Depolarizing neuromuscular blocker

IND: Rapid sequence induction

TOX: Malignant hyperthermia when given with halogenated inhaled anesthetic; contraindicated in patients with glaucoma because of ↑ intraocular pressure (IOP)

Tubocurarine

MOA: Nondepolarizing neuromuscular blocker

IND: Adjuvant to general anesthesia

TOX: Hypotension

Why is epinephrine commonly combined with local anesthetics?

To prolong the duration of the anesthetic effect by causing local vasoconstriction

What types of fibers are affected most by local anesthetic agents?

Pain > temperature > touch > pressure; small unmyelinated fibers most affected; large, myelinated fibers least affected

Which drug is used to reverse the effects of the nondepolarizing muscle blockers?

Neostigmine

Which drug is used to treat malignant hyperthermia?

Dantrolene

Analgesics

For each of the following drugs, provide:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects and unique toxicity (TOX) (if any)

Acetaminophen

MOA: COX inhibitor

IND: Pain, fever (but not used as anti-inflammatory)

TOX: Overdose causes hepatic necrosis

Aspirin

MOA: Irreversible inhibition of COX-1 and COX-2

IND: Analgesic, antipyretic, anti-inflammatory, antiplatelet drug

TOX: GI ulcers, platelet dysfunction, hypersensitivity reactions, bronchoconstriction, tinnitus, Reye syndrome in children

Celecoxib

MOA: COX-2 inhibitor

IND: Osteoarthritis, rheumatoid arthritis

TOX: Similar to aspirin but less GI toxicity

Gabapentin

MOA: Structural analog of GABA

IND: Neuropathic pain

TOX: Sedation, movement disorders

Indomethacin

MOA: Reversible inhibition of COX-1 and COX-2

IND: Acute gout, neonatal patent ductus arteriosus

TOX: GI upset, headache

Meperidine

MOA: μ opioid receptor agonist

IND: Analgesic

TOX: Seizures; side effects similar tomorphine

Morphine

MOA: μ opioid receptor agonist; opioid receptor binding activates G proteins and adenylyl cyclase.

IND: Analgesic, cough suppressant.

TOX: Constipation, emesis, sedation, respiratory depression, miosis, urinary retention.

Note: these symptoms are typical for heroin overdose.

Nalbuphine

MOA: Opioid mixed agonist-antagonist analgesic that activates K and weakly blocks μ receptors

IND: Analgesic with less abuse potential

Naloxone

MOA: μ opioid receptor antagonist

IND: Used to reverse the effects of opioid agonists

TOX: CNS depression

What two types of opioid receptors mediate analgesia, respiratory depression, and physical dependence?

1. μ

2. δ

What type of opioid receptors mediate spinal analgesia and the sedative effects of opioids?

K

CHAPTER 5

Cardiovascular

EMBRYOLOGY

What are the five dilatations of the primitive heart tube?

1. Truncus arteriosus

2. Bulbus cordis

3. Primitive ventricle

4. Primitive atrium

5. Sinus venosus

Name the structures in the mature heart that are derived from the following embryonic structures:

Truncus arteriosus

Ascending aorta and pulmonary trunk

Bulbus cordis

Smooth parts of left (aortic vestibule) and right (conus arteriosus) ventricle

Primitive ventricle

Trabeculated parts of left and right ventricle

Primitive atria

Trabeculated parts of left and right atria

Left horn of sinus venosus

Coronary sinus

Right horn of sinus venosus

Smooth part of right atrium (sinus venarum)

Transient common pulmonary vein

Smooth part of left atrium

Right common cardinal vein and right anterior cardinal vein

Superior vena cava

Which embryonic layer gives rise to most of the cardiovascular system?

Mesoderm

What structure divides the truncus arteriosus and bulbus cordis?

Aorticopulmonary septum

Name the structure between the atria that develops from the walls of the septum primum and septum secundum:

Foramen ovale

Name the three physiologic shunts in the fetal circulation and the structures they shunt between:

1. Foramen ovale (right to left atrium)

2. Ductus arteriosus (pulmonary artery to aortic arch)

3. Ductus venosus (umbilical vein to IVC)

ANATOMY

What are the two anatomic divisions of the pericardium?

1. Serous pericardium (made of visceral epicardial layer and parietal layer)

2. Fibrous pericardium

Which nerve lies between the fibrous paricardium and mediastinal pleura?

Phrenic nerve (runs with pericardiophrenic vessels)

Name the chamber associated with each heart surface:

Sternocostal surface

Right ventricle

Posterior surface (base)

Left atrium

Diaphragmatic surface

Right and left ventricles

Pulmonary surface and apex

Left ventricle

Name the structures that compose each heart border:

Right border

Right atrium

Left border

Left ventricle, left auricle

Inferior border

Right ventricle

Superior border

Right and left auricles, great vessels

Name the major artery that commonly supplies each of the following structures:

Right atrium and right ventricle

Right coronary artery (RCA)

Sinoatrial (SA) and atrioventricular (AV) nodes

RCA

Left atrium and left ventricle

Left coronary artery (LCA)

Interventricular septum

1. Anterior 2/3

2. Posterior 1/3

1. Left anterior descending (LAD)

2. Posterior interventricular artery

Which artery determines dominance of cardiac blood supply?

Posterior interventricular artery

What are the most common sites for coronary occlusion?

Left anterior descending (LAD) > RCA > circumflex

Trace the general pathway of venous drainage from myocardium.

Great, middle, and small cardiac veins → coronary sinus → right atrium

Trace the conduction pathway of a cardiac impulse.

SA node → AV node → bundle of His → right and left bundle branches → Purkinje fibers

Which nerve supplies parasympathetic input to heart?

Vagus nerve

Which syndrome is characterized by arm claudication, syncope, vertigo, nausea, and a supraclavicular bruit?

Subclavian steal syndrome (occlusion in subclavian artery proximal to take vertebral artery take-off → “stealing” of blood from vertebral artery to distal subclavian artery)

Describe the best location for auscultation of the following cardiac valves:

Tricuspid valve

Left sternal border, fifth intercostal space

Pulmonary valve

Left sternal border, second intercostal space

Mitral valve

Apex of heart, fifth intercostal space

Aortic valve

Right sternal border, second intercostal space

PHYSIOLOGY

Cardiac Electrophysiology

Name the electrical event in the heart associated with each feature of a normal electrocardiogram:

P wave

Atrial depolarization

PR interval

Atrial depolarization and conduction delay through AV node

QRS complex

Depolarization of the ventricles

T wave

Ventricular repolarization

Which ion primarily dictates the resting membrane potential of a myocyte?

Potassium. Membrane has high K+ permeability through K+ channels.

Which membrane protein maintains the ion gradient?

Sodium-potassium ATPase

What is the effect of potassium efflux from a myocardial cell?

Hyperpolarization

What is the effect of potassium influx into a myocardial cell?

Depolarization

Describe the electrochemical events that cause the following phases of the cardiac myocyte action potential:

Phase 0 (the upstroke)

Influx of Na+ into cell

Phase 1 (initial repolarization)

Efflux of K+ out of cell and ↓ Na+ influx

Phase 2 (the plateau)

Influx of Ca2+ into cell, efflux of K+ out of cell

Phase 3 (repolarization)

Efflux of K+ out of cell

Phase 4 (resting membrane potential)

Equilibrium potential, balance between K+ leak current and Na+/K+ ATPase

What unique electrochemical feature of SA node allows it to act as a pacemaker for the heart?

Phase 4 depolarization causing automaticity

What ion and channel are responsible for automaticity?

Na+ conductance via If channel.

Describe the electrochemical events that cause the following phases of the SA nodal action potential:

Phase 0 (the upstroke)

Influx of Ca2+ into cell

Phase 3 (repolarization)

Efflux of K+ out of cell

Phase 4 (slow depolarization)

Increasing Na+ influx into cell

What phase 4 characteristic determines heart rate?

Slope which represents rate of depolarization

Name the component of the cardiac conduction system where phase 4 depolarization is fastest:

SA node

Name the component of the cardiac conduction system where phase 4 depolarization is slowest:

Bundle of His and Purkinje fibers

Define conduction velocity.

The rate at which an impulse spreads throughout cardiac tissue

What determines conduction velocity?

Rate of depolarization (phase 0 upstroke)

Where is conduction velocity fastest?

The Purkinje system

Where is conduction velocity slowest?

The AV node

What is the significance of the conduction delay at the AV node?

The delay in conduction allows for ventricular filling

Cardiac Contractility and Output

Describe the function of each myocardial cellular component:

Sarcomere

Contractile unit

Intercalated disks

Cell adhesion

Gap junction

Electrochemical communication between myocardial fibers

T tubules

Carry action potentials into the cell interior

Sarcoplasmic reticulum

Storage and release of calcium

Which ion determines the magnitude of tension in a contracting myocardial cell?

Amount of intracellular calcium

Describe the effect of each of the following on contractility:

Increased heart rate

Increased contractility

Catecholamines

Increased contractility

Digoxin

Increased contractility

Acetylcholine (ACh)

Decreased contractility

What is the Frank-Starling relationship?

The greater the end-diastolic volume (preload), the greater is the stroke volume.

How does contractility affect cardiac output?

Cardiac output increases as contractility increases.

Name the four factors that determine myocardial oxygen consumption:

1. Afterload

2. Size of heart (wall tension)

3. Contractility

4. Heart rate

Provide formulas for each of the following:

Stroke volume

End-diastolic volume − end-systolic volume =

Cardiac output

Stroke volume × heart rate =

Ejection fraction

Stroke volume/end-diastolic volume =

Stroke work

Aortic pressure × stroke volume

Cardiac output based on Fick principle

O_2 consumption/(arterial O_2 - venous O_2)

Heart Sounds

Name the event associated with eachheart sound:

S_1

Closure of the AV (tricuspid, mitral)valves

S_2

Closure of semilunar (aortic, pulmonary) valves

S_3

Flow of blood from atria into ventriclesduring diastole (often seen with largeventricular volumes, ie, CHF; oftenbenign in youth and trained athletes)

S_4

Flow of blood from atria into ventriclesduring atrial systole (often present inpatient with stiffened ventricle)

Maintenance of Blood Pressure

What is the site of highest resistance in the cardiovascular system?

Arterioles

Which vascular bed has the largest cross-sectional and surface areas?

Capillaries

Which vascular bed contains the largest volume of blood at any given time?

Veins

Define the following terms:

Systolic blood pressure

Highest arterial blood pressure during acardiac cycle

Diastolic blood pressure

Lowest arterial blood pressure during acardiac cycle

Pulse pressure

Difference between systolic and diastolicblood pressure

What is the most important determinant of pulse pressure?

Stroke volume

What is the effect of aging on pulse pressure?

Aging widens pulse pressure due to ↓ capacitance of blood vessels

How is left atrial pressure estimated clinically?

Pulmonary capillary wedge pressure

Where are the carotid baroreceptors located?

Bifurcation of common carotid arteries

What is the function of the carotid baroreceptors?

Minute to minute regulation of blood pressure

Which nerve carries information from baroreceptors to the vasomotor center in the brainstem?

Cranial nerve IX

Describe the phases of the Valsalva maneuver and changes occurring with BP and heart rate.

Phase 1: forceful expiration against closed glottis (↑ BP with ↑ intrathoracic pressure, ↓ HR with baroreflex)

Phase 2: accommodation (↓ BP with reduced venous return, ↑ HR with baroreflex)

Phase 3: breathe in (↓ BP with ↓ intrathoracic pressure, ↑ HR with baroreflex)

Phase 4: recovery (↑ BP with normal venous return, marked ↓ HR with baroreflex overshoot)

Name two ways that the vasomotor center responds to decreased mean arterial pressure:

1. ↓ Parasympathetic output

2. ↑ Sympathetic output

Name the hormone(s) responsible for each of the following functions:

Long-term regulation of blood pressure

Renin-angiotensin-aldosterone system

Stimulation of aldosterone secretion and arterial vasoconstriction

Angiotensin II

Water retention and direct arteriolar vasoconstriction causing an increase in blood pressure

Vasopressin

Inhibition of renin release, stimulation of salt and water excretion, and vascular smooth muscle relaxation

Atrial natriuretic peptide

Name three stimuli for renin secretion:

1. ↓ Renal blood pressure

2. ↓ Na+ delivery to macula densa of JGA

3. ↑ Sympathetic tone

What is the effect of cerebral ischemia on blood pressure and heart rate?

Cushing reflex: blood pressure ↑ and heart rate ↓

What is the mechanism of increased blood pressure in cerebral ischemia?

Chemoreceptors in the vasomotor center stimulate increased sympathetic outflow

What is the mechanism of decreased heart rate in cerebral ischemia?

Baroreceptor reflex to increase in BP leads to increased parasympathetic outflow to heart

Where are the carotid chemoreceptors located?

Bifurcation of common carotid arteries and the aortic arch at carotid body

What do chemoreceptors sense?

Oxygen, CO_2, pH, and temperature

What is the Starling equation?

Jv = Kf [(Pc - Pi) - (πc − πi)]

Describe the effect of each of the following on capillary filtration:

Increased capillary hydrostatic pressure

Increased fluid filtration

Increased interstitial hydrostatic pressure

Decreased fluid filtration

Increased capillary oncotic pressure

Decreased fluid filtration

Increased interstitial oncotic pressure

Increased fluid filtration

Define autoregulation.

The capacity of an organ to maintain constant blood flow despite changes in mean arterial pressure

Define active hyperemia.

The capacity of an organ to increase blood flow in response to metabolic demands

Name the primary mechanism of blood flow regulation in the following tissues:

Coronary arteries

Local metabolic control

Cerebral vasculature

Local metabolic control

Muscle

Local metabolic control

Skin

Sympathetic control

Pulmonary

Local metabolic control

Name five key metabolites which cause vasodilation:

1. Lactate

2. K+

3. Adenosine

4. CO_2

5. H+

Name the primary vasoactive metabolite in the following tissues:

Coronary arteries

O_2, adenosine

Cerebral vasculature

CO_2 (most important), H+

Muscle

Lactate, K+, adenosine

Pulmonary

O_2

CARDIOVASCULAR PATHOLOGY AND PATHOPHYSIOLOGY

Murmurs

Name the valvular defect causing each murmur described below:

Harsh midsystolic murmur in the left second intercostal space at the left sternal border

Pulmonic stenosis

Harsh midsystolic murmur in the right second intercostal space at the right sternal border, radiating to the neck (carotid arteries) and apex

Aortic stenosis

Harsh midsystolic murmur at the left third and fourth interspaces radiating down the left sternal border; murmur louder with decreased preload (ie, on Valsalva); S_4 and biphasic apical impulse often present

Hypertrophic cardiomyopathy

Blowing holosystolic murmur at apex radiating to the left axilla with increased apical impulse

Mitral regurgitation

Blowing holosystolic murmur at the lower left sternal border radiating to the right of the sternum; may ↑ with inspiration

Tricuspid regurgitation

Soft, late systolic murmur at the left sternal border or apex, accompanied by midsystolic click

Mitral valve prolapse

Harsh holosystolic murmur at the lower left sternal border, accompanied by a thrill

Ventricular septal defect (VSD)

Blowing, high-pitched diastolic murmur at the left second to fourth interspaces radiating to the apex

Aortic regurgitation

Low-pitched diastolic murmur at the apex that gets louder prior to S_1; an opening snap is often present just after S_2

Mitral stenosis

Systolic flow murmur at left upper sternal border; fixed splitting of S_2

Atrial septal defect (ASD)

What congenital valvular defect is associated with aortic stenosis?

Bicuspid aortic valve

What are two common manifestations of aortic stenosis?

Angina and syncope

Which disorder results from myxomatous degeneration of the mitral valve?

Mitral valve prolapse

Patients with mitral valve prolapse are at increased risk of which infection?

Infective endocarditis

Heart Failure

What are the most common causes of left-sided heart failure?

Ischemic heart disease, HTN, mitral and aortic valvular disease, myocardial disease (cardiomyopathy, myocarditis)

Name four key mechanisms of compensation in congestive heart failure (CHF):

1. Hypertrophy

2. Ventricular compensation

3. Blood volume expansion

4. Tachycardia

Name two major clinical signs/symptoms of left-sided heart failure:

1. Pulmonary congestion

2. Pulmonary edema causing dyspnea and orthopnea

Name three consequences of suboptimal renal perfusion:

1. RAA axis activation leading to salt and water retention

2. Ischemic acute tubular necrosis (ATN)

3. Prerenal azotemia

What is the consequence of impaired cerebral perfusion in CHF?

Hypoxic encephalopathy

What is the most common cause of right-sided heart failure?

Left-sided heart failure

Name two major pulmonary causes of right-sided heart failure:

1. Interstitial fibrosis

2. Pulmonary HTN

Name four key clinical signs of right-sided heart failure:

1. Portal, systemic, peripheral congestion, and edema

2. Hepatomegaly

3. Congestive splenomegaly

4. Renal congestion

Describe the phases of pathologic change in the liver that result from chronic right-sided heart failure.

Nutmeg appearance → centrilobular necrosis → central hemorrhagic necrosis → cardiac sclerosis (cirrhosis)

What is the most common cause of acute right-sided heart failure in a patient with a deep venous thrombosis?

Massive pulmonary embolus

What EKG findings may be seen with acute right-sided heart stress?

S_1Q_3T_3: S wave in lead 1, Q wave in lead 3, T-wave inversion in lead 3

Ischemic Heart Disease

Name four important manifestations of ischemic heart disease:

1. Angina

2. Myocardial infarction (MI)

3. Lethal arrhythmia causing sudden cardiac death

4. Chronic CHF

What are the two major etiologies of myocardial ischemia?

1. ↓ Coronary perfusion

2. ↑ Myocardial O_2 demand

What conditions compound the consequences of impaired myocardial perfusion?

Anemia, advanced lung disease, cigarette smoking, congenital heart disease

Name the type of angina:

Pain precipitated by exertion, relieved by rest/vasodilators

Stable angina

Paroxysmal chest pain at rest in patient with or without coronary risk factors

Prinzmetal angina

Severe substernal pain/pressure at rest

Unstable angina

Describe the underlying pathology for each type of angina:

Stable angina

Greater than 75% occlusion of coronary artery

Prinzmetal angina

Coronary vasospasm

Unstable angina

Plaque disruption with resulting occlusive thrombosis within a coronary artery

Describe the associations between myocardial ischemia, injury, and infarction.

1. Ischemia—insufficient blood supply to the myocardium, occurs first

2. Injury—results when the ischemic process is prolonged

3. Infarction—describes necrosis or death of myocardial cells

Name the type of myocardial damage described below:

Full-thickness infarction caused by complete occlusion of a coronary artery

Transmural infarction

Infarction of the inner half (or less) of the ventricular wall supplied by a partially occluded coronary artery

Subendocardial infarction

T-wave inversion on ECG

Transmural ischemia

ST depression on ECG

Subendocardial injury

ST elevation on ECG

Transmural injury

Q waves present on ECG

Transmural infarction

What is the initial event in the development of a transmural infarction?

Acute plaque disruption

What are the most common symptoms of a myocardial infarct?

Crushing retrosternal chest pain or pressure, dyspnea, pain radiating into left arm or neck, diaphoresis, nausea

What type of necrosis is seen in myocardium within 24 hours of infarction?

Coagulative necrosis

What type of inflammatory cells are seen in the myocardium within 24 hours of infarction?

Neutrophils

What is the most common type of inflammatory cell seen in myocardium from the 2nd to 10th day after an infarction?

Macrophages

When is the risk of myocardial rupture greatest and why?

At 4 to 7 days. Tissue is weakest following phagocytosis of debris by macrophages and prior to growth of granulation tissue.

How many days does it take to form granulation tissue in a region of infarcted myocardium?

7 to 10 days

How many weeks does it take to form contracted scar tissue in a region of infarcted myocardium?

7 weeks

What is the diagnostic test of choice in a patient with suspected MI?

ECG

What two classic ECG changes are seen during an MI?

1. Q waves

2. ST elevation

When does CK-MB begin to rise, peak, and return to normal?

Rise: 3 to 8 hours

Peak: 10 to 24 hours

Return to normal: 2 to 3 days

When does troponin I begin to rise, peak, and return to normal?

Rise: 3 to 8 hours

Peak: 24 to 48 hours

Return to normal: 5 to 10 days

What are the advantages and disadvantages of the CK-MB serum cardiac marker?

Allows diagnosis of re-infarction as levels quickly return to normal; may be falsely elevated with skeletal muscle injury

What are the advantages of the Troponin test?

Very specific to cardiac injury; allows diagnosis of late presenting MI

What are the two most common complications of MI?

1. Cardiac arrhythmia

2. CHF

List five less common but severe complications of MI:

1. Cardiogenic shock

2. Ventricular aneurysm or rupture

3. Papillary muscle rupture

4. Mural thrombosis with resulting peripheral embolism

5. Dressler syndrome

Cardiomyopathy

How does the left ventricle respond to long-standing HTN?

Concentric hypertrophy

What are the three types of cardiomyopathy?

1. Dilated or congestive

2. Hypertrophic

3. Restrictive

What are the most common nongenetic etiologies of dilated cardiomyopathy?

“ABCDE”

Alcohol abuse

Beriberi (thiamine deficiency)

Coxsackie Bmyocarditis, Cocaine, Chagas disease

Doxorubicin toxicity

prEgnancy

Name the type of cardiomyopathy associated with the following clinical and pathologic features:

30% to 40% of cases are genetic

Dilated

100% of cases are genetic

Hypertrophic

Associated with alcoholism and thiamine deficiency

Dilated

Associated with coxsackie virus B and with Trypanosoma cruzi

Dilated

Associated with doxorubicin

Dilated

Associated with eosinophilia

Restrictive (Loeffler endocarditis)

Associated with pregnancy

Dilated

Asymmetric septal hypertrophy, banana-shaped left ventricle without dilatation

Hypertrophic

Can be caused by sarcoidosis, amyloidosis, scleroderma, hereditary hemochromatosis, endocardial fibroelastosis, radiation-induced fibrosis

Restrictive

Cardiomyopathy most commonly caused by endomyocardial fibrosis

Restrictive

Causes sudden death in young, otherwise healthy athletes

Hypertrophic

Commonly inherited in an autosomal-dominant (AD) fashion

Hypertrophic

Four-chamber hypertrophy and dilation

Dilated

Left ventricular outflow obstruction

Hypertrophic

Myocyte tangles, disorientation

Hypertrophic

Symptoms relieved by squatting

Hypertrophic

Pericarditis and Cardiac Tumors

Name the type of pericarditis based on the following exudates descriptions:

Clear, straw colored, minimal inflammation, decreased fibrin

Serous pericarditis

Fibrin rich

Fibrinous pericarditis

Bloody

Hemorrhagic pericarditis

What are the most common etiologies of serous pericarditis?

Uremia, systemic lupus erythematosus (SLE), rheumatic fever

What are the most common etiologies of fibrinous pericarditis?

Uremia, SLE, rheumatic fever, coxsackie viral infection, MI, trauma

What are the most common etiologies of hemorrhagic pericarditis?

Trauma, malignancy, tuberculosis

What ECG and BP findings are seen in pericarditis?

ECG: diffuse ST elevations in all leads

BP: pulsus paradoxus

What is the most common cardiac tumor of adults?

Metastases (eg, melanoma)

What is the most common primary cardiac tumor of adults?

Left-sided atrial myxoma

What is the most common primary cardiac tumor in children?

Rhabdomyoma, commonly associated with tuberous sclerosis

Congenital Heart Disease

Name the congenital heart defect associated with each of the following statements:

Three most common causes of R->L shunting

1. Atrial septal defect (ASD)

2. VSD

3. Patent ductus arteriosus (PDA)

Two most common defects

1. VSD

2. PDA

Five defects causing cyanosis at birth

“5 T’s”:

1. Tetralogy of Fallot

2. Transposition of the great vessels

3. Truncus arteriosus

4. Total anomalous pulmonary venous return

5. Tricuspid atresia

Continuous machinery-like murmur

PDA

Pulmonic stenosis, right ventricular hypertrophy, overriding aorta, VSD (“PROVe”)

Tetralogy of Fallot

Boot-shaped cardiac silhouette

Tetralogy of Fallot

Defect causing lower body cyanosis

Preductal coarctation

Defect causing upper extremity HTN and diminished lower extremity pulses

Postductal coarctation (stenosis distal to the ductus arteriosus)

Associated with Turner syndrome

Coarctation of the aorta

Associated with Down syndrome

ASDs, VSDs, and AV valve abnormalities (due to endocardial cushion abnormalities)

Associated with Rubella

Patent ductus arteriosus

Associated with 22q11 syndrome

Truncus arteriosus, Tetralogy of Fallot

Common cyanotic congenital heart defect in children born to diabetic mothers

Transposition of the great vessels

Aorta arises from right ventricle and pulmonary trunk arises from left ventricle

Transposition of the great vessels

Valvular defect associated with increased risk of infective endocarditis and calcification

Bicuspid aortic valve

What is the consequence of leaving a left-to-right shunting untreated?

Right → left shunting

What type of infection are patients with VSD at an increased risk for?

Infective endocarditis

What drug is used to induce closure of a PDA?

Indomethacin

What drug is used to prevent closure of a PDA?

Prostaglandins

What is the most common genetic cause of congenital heart disease?

Trisomy 21

Cardiac Infectious Disorders

What type of infection is responsible for causing rheumatic fever?

Group A streptococcal pharyngitis

How does streptococcal pharyngitis cause rheumatic heart disease?

Antistreptococcal antibodies cross-react with a cardiac antigen

What serologic test is elevated in rheumatic heart disease:

Antistreptolysin antibodies (ASO)

Name the five major Jones criteria for rheumatic heart disease:

1. Joints: migratory polyarthritis

2. ♥ (o) = pancarditis

3. Nodules: subcutaneous nodules

4. Erythema marginatum

5. Syndeham chorea

Name five minor Jones criteria for rheumatic heart disease:

1. Fever

2. Arthralgia

3. Elevated ESR/CRP

4. Leukocytosis

5. Heart block on ECG

What term is used to describe the foci of pink collagen surrounded by lymphocytes and Anitschkow cells (macrophages) that are pathognomonic for rheumatic heart disease?

Aschoff bodies

Which valve is most commonly affected in rheumatic heart disease?

Mitral valve

What is the most commonly observed valvular deformity in rheumatic heart disease?

Fishmouth or buttonhole stenosis of the mitral valve

What are the three major categories of endocarditis?

1. Infective

2. Nonbacterial thrombotic or marantic

3. Libman-Sacks

What is the most common valve affected by bacterial endocarditis?

Mitral valve

What is the most common valve affected by bacterial endocarditis in IV drug users?

Tricuspid valve

Name the type of endocarditis described in each of the following vignettes:

25-year-old (y/o) IV drug user with rapid onset of high fever, rigors, malaise, and tricuspid regurgitation

Acute infective endocarditis

60-y/o woman with mitral valve prolapse, who has recently undergone dental extraction, presents with low-grade fever and flu-like symptoms

Subacute infective endocarditis

65-y/o man with metastatic colon cancer and new murmur consistent with mitral regurgitation

Nonbacterial thrombotic endocarditis

30-y/o woman with SLE

Libman-Sacks endocarditis

Which organism most often causes acute infective endocarditis?

Staphylococcus aureus

Which organism most often causes subacute infective endocarditis?

Streptococcus viridians

What are the clinical signs of bacterial endocarditis?

Fever

Roth spots

Osler nodes

Murmur

Janeway lesions

Anemia

Nail bed hemorrhages

Emboli

Define the following eponyms used to describe signs of bacterial endocarditis:

Osler nodes

Tender, raised lesions on finger and toe pads

Janeway lesions

Small, erythematous lesions on palms and soles

Roth spots

Erythematous spots with white centers on retina

What are some sequelae to bacterial endocarditis?

Valvular injury, renal injury (glomerulonephritis), septic emboli to brain, kidneys causing infarction or abscess

Atherosclerosis

What are the major risk factors for coronoary heart disease?

Age (men > 45, women > 55 or with premature menopause)

Family history of premature heart attacks (MI or sudden cardiac death in men 55, women 65)

Cigarette smoking

Hypertension (HTN)

HDL 40, HDL > 60 negates one risk factor

What are the two main histopathologic components of an atheroma?

Superficial fibrous cap overlying a necrotic core

What are the components of the fibrous cap?

Smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, and elastin.

What is the pathologic precursor to atheroma?

Fatty streak

What is the term for ulcerated, calcified, hemorrhagic atheromas that predispose to thrombosis?

Complicated plaques

What is the underlying pathologic basis for the initiation of atherosclerosis?

Endothelial injury

What may produce this endothelial injury?

Hypercholesterolemia, mechanical injury, HTN, immune mechanisms, toxins, etc.

How are foam cells created?

Macrophages that ingest oxidized LDL that has accumulated in the vessel wall become foam cells.

Which lipids are most commonly found in an atheromatous plaque?

Cholesterol and cholesterol esters (LDL)

What is the function of smooth muscle cells in an atheroma?

Smooth muscle cells when activated by growth factors proliferate and migrate into intima. They then secrete extracellular matrix glycoproteins.

What are the major cell types associated with the formation of an atheroma?

Macrophages (foam cells), T lymphocytes (attracted to zone of injury), smooth muscle cells, and endothelial cells

What are the most common locations for atherosclerotic disease?

Abdominal aorta, coronary arteries, popliteal arteries, and carotid arteries

What are the four major clinical manifestations of atherosclerosis?

1. Arterial insufficiency (ie, stroke, MI, peripheral vascular disease, ischemic bowel disease)

2. Thrombus formation due to plaque rupture

3. Atheroembolism

4. Aneurysm, dissection, or rupture of a major vessel

Arteriolosclerosis

Name the type of arteriolosclerosis associated with the following clinical and pathologic features:

Hyaline deposits causing thickening of arteriolar walls

Hyaline arteriolosclerosis

Onion skin arteriolar thickening

Hyperplastic arteriolosclerosis

Deposition of calcium in the medial coat of arteries of the lower extremities

Monckeberg arteriosclerosis

Pipestem arteries with ringlike calcifications

Monckeberg arteriosclerosis

Two types of arteriolosclerosis that occur in patients with long-term HTN

1. Hyaline arteriolosclerosis

2. Hyperplastic arteriolosclerosis

Hypertension

HTN is the most important risk factor in which two vascular diseases?

1. Coronary artery disease

2. Cerebrovascular disease

What percentage of hypertensive patients have essential HTN?

90% to 95%

What are two common renal causes of secondary HTN?

1. Renal artery stenosis

2. Renal parenchymal disorders

What are some common endocrine causes of secondary HTN?

1. Pheochromocytoma

2. Conn syndrome (primary aldosteronism)

3. Hyperthyroidism

4. Oral contraceptive use

5. Cushing syndrome

6. Acromegaly

Name two common cardiac complications of long-standing HTN:

1. Left ventricular hypertrophy

2. Left-sided heart failure (a result of secondary to left ventricular hypertrophy)

Define hypertensive urgency and emergency.

Urgency: blood pressure > 200/120 without symptoms

Emergency: blood pressure > 200/120 with symptoms or evidence of end organ damage

List the possible effects of malignant HTN on each organ system below:

Heart

Acute LV failure, MI

Aorta

Dissection

Lungs

Pulmonary edema

Kidneys

Acute renal failure

Eyes

Papilledema, fundal hemorrhages, blurred vision

Brain

Headache, encephalopathy, seizure, hemorrhagic cerebrovascular accident (CVA)

What is the most common cause of death in patients with untreated HTN

Coronary artery disease

Aneurysms and Dissection

What is the most common site for atherosclerotic aneurysm?

Abdominal aorta, below renal arteries and above iliac bifurcation

What is the most common site for syphilitic aneurysm?

Thoracic aorta (often ascending)

What is the mechanism of syphilitic aneurysms?

Obliteration of the arteries supplying the aorta (endarteritis obliterans), leading to necrosis of the media

Name the type of aneurysm referred to in the following clinical vignettes:

55-y/o man, who is a smoker with HTN, diabetes, and coronary artery disease, is found to have a pulsatile midline abdominal mass.

Atherosclerotic, abdominal aortic aneurysm

35-y/o with a family history of polycystic kidney disease presents with the worst headache of his life.

Berry Aneursym rupture leading to subarachnoid hemorrhage

40-y/o prostitute with angina and shortness of breath (SOB) is found to have wide pulse pressure and a high-pitched blowing diastolic murmur.

Syphilitic/luetic, dilation of aortic root leads to aortic regurgitation

What are the most common etiologies for the development of aortic dissection?

HTN and connective tissue disorders (such as Marfan syndrome)

Name two characteristic histopathologic findings in the aorta in a patient with Marfan syndrome:

1. Elastic tissue fragmentation

2. Cystic medial degeneration

What is the genetic defect in Marfan disease?

Defect in fibrillin-1 which forms a scaffold for elastic fibers.

What is the classic clinical presentation of aortic dissection?

Sudden onset of severe tearing pain radiating to the back and descending as the dissection progresses

What is the underlying mechanism in the development of varicose veins?

Venous dilation or deformation leading to venous valvular incompetence

State two complications of varicose veins:

1. Varicose ulceration

2. Stasis dermatitis

Vasculitides

Name the type of vasculitis associated with the following clinical and pathologic features:

Presence of C-ANCA

Wegener granulomatosis

Presence of P-ANCA

Microscopic PolyANgiitis, PolyArteritis Nodosa (PAN), and Churg-Strauss syndrome

Most common vasculitis in the United States

Temporal or giant cell arteritis

Fibrous thickening of origins of the great vessels leading to absent pulses

Takayasu arteritis

Well-demarcated, segmental fibrinoid necrosis of the arterial wall and diffuse neutrophilic infiltrates in medium-sized arteries

PAN

Commonly affecting the coronary arteries and may result in coronary aneurysm

Kawasaki disease

Segmental inflammation/thrombosis of arteries and adjacent veins, nerves, and connective tissue; results in painful ischemic disease and associated with smoking

Buerger disease (Thromboangiitis obliterans)

Vascular and mesangial deposition of IgA complexes with abdominal pain, palpable purpura especially on buttocks, glomerulonephritis, and arthritis

Henoch-Schonlein purpura

Which vessels are most commonly involved in temporal arteritis?

External carotid artery and its branches

What is the triad of Wegener granulomatosis?

1. Focal necrotizing vasculitis of upper airways and lungs

2. Necrotizing granulomas of upper and lower respiratory tract

3. Necrotizing glomerulitis

What are the six clinical signs of acute arterial occlusion?

“Six P’s”:

1. Pain

2. Pallor

3. Poikilothermia

4. Paresthesia

5. Paralysis

6. Pulselessness

Name the type of vasculitis associated with each of the following clinical vignettes:

70-y/o white man with constitutional symptoms, headache, jaw claudication, acute onset of blindness; W/U: ↑ ESR

Temporal (giant cell) arteritis

30-y/o Korean woman with constitutional symptoms, arthritis; physical examination (PE): loss of carotid and radial pulses

Takayasu arteritis

35-y/o hepatitis B positive man with fever, HTN; W/U: neutrophilia, P-ANCA ⊕

PAN

12-y/o girl recovering from a viral infection presents with exertional chest pain; PE: febrile, conjunctival injection, cervical lymphadenopathy, strawberry tongue, diffuse erythematous rash, edema of hands and feet

Kawasaki disease

40-y/o man with asthma; PE: palpable purpura, diffuse wheezes; CBC: eosinophilia; transbronchial biopsy: upper airway granulomas and elevated P-ANCA and ESR

Churg-Strauss syndrome

8-y/o boy presents with abdominal pain, hematuria, and recent history of URI; PE: palpable purpura, heme ⊕ stools; W/U: vascular biopsy shows perivascular granulocytes, IgA deposition

Henoch-Schonlein purpura

55-y/o man presents with chronic cough, rhinorrhea, ulcerations of nasal septum; W/U: RBC casts in urine and C-ANCA ⊕

Wegener granulomatosis

21-y/o woman smoker with pallor and cyanosis of fingertips after exposure to cold

Raynaud disease

Vascular Tumors

Name the vascular disorder associated with the following clinical or pathologic features:

Most common tumor of infancy

Port-wine stain birthmark

Cutaneous vascular tumor commonly seen in patients with end-stage liver disease (hyperestrinism)

Spider telangiectasia

AD condition is characterized by a localized dilation of venules and capillaries in skin and mucous membrane leading to epistaxis and GI bleeding

Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber) syndrome

AD condition is characterized by the presence of multiple cavernous hemangiomas of skin, liver, pancreas, and spleen and hemangioblastomas of cerebellum with ↑ risk of renal cell carcinoma

von Hippel-Lindau disease

Vascular tumor associated with thorium contrast material and polyvinyl chloride

Hemangiosarcoma

Vascular tumor commonly seen in men of eastern European descent and in those infected with HIV consisting of red or purple cutaneous plaques on the lower extremities

Kaposi sarcoma

Vascular tumor caused by human herpesvirus (HHV) 8 or HIV

Kaposi sarcoma

Syndrome is characterized by cyanosis and edema of upper extremities, head, and neck in a patient with bronchogenic carcinoma

Superior vena cava syndrome

PHARMACOLOGY

Antianginal Agents

What are the three classes of antianginal drugs?

1. Organic nitrates

2. β-Blockers

3. Calcium channel blockers

How do nitrates cause vasodilation?

Nitrates are metabolized to nitric oxide (NO) → NO causes ↑ in cyclic guanosine monophosphate (cGMP) in endothelial cells → vasodilation

Describe how nitrates reduce angina.

1. Vasodilation causes venous pooling, which reduces preload and consequently myocardial oxygen consumption.

2. Coronary vasodilation improves oxygen delivery to the myocardium.

What is the most common side effect of nitrates?

Headache

Describe how each of the following drugs reduces angina:

β-Blockers

By ↓ contractility and heart rate

Nifedipine

Coronary arteriaolar vasodilation

Verapamil

Decreased heart rate and contractility, slowed conduction (especially through AV node)

What is the antianginal drug of choice for Prinzmetal angina?

Diltiazem

What antianginal drug is contraindicated in patients with asthma and COPD?

β-Blockers

Inotropic Support

Name the only oral inotropic agent:

Digoxin

Describe the three-step mechanism by which digitalis potentiates myocardial contractility.

1. Inhibition of Na+/K+ ATPase.

2. Buildup of intracellular Na+.

3. High intracellular Na+ impairs Na+-Ca2+ antiport, causing increased intracellular Ca2+.

What is the unique side effect of digoxin on the heart?

Dysrhythmia

Which agent can be used to counteract the cardiac toxicity of digoxin? By what mechanism?

K+ supplementation. Digoxin binds near K+ site on Na+/K+ ATPase. When K+ is low, digoxin has better access and vice versa.

What are the unique neurotoxicities of digoxin?

Headache, nausea, altered color perception, blurred vision, tinnitus

For which arrhythmia is digoxin commonly used?

Atrial fibrillation

What is the β-agonist of choice for inotropic support in heart failure?

Dobutamine

Which antiarrhythmic is useful for abolishing torsades de pointes and digoxin toxicity?

Mg2+

By which mechanism do β-agonists and phosphodiesterase inhibitors potentiate myocardial contractility?

These agents increase cAMP which promotes increased intracellular Ca2+.

Antiarrhythmics

For each class of antiarrhythmic agent, state the mechanism of action. (Note: many of these agents have multiple mechanisms of action.):

IA

Na+ channel blocker, some K+ blockade

IB

Na+ channel blocker

IC

Na+ channel blocker

II

β+ blockade

III

K+ channel blocker

IV

Ca2+ channel blocker

For each class of antiarrhythmic agent, describe how the myocyte action potential is affected:

IA

Slows phase 0 depolarization, slows phase 3 repolarization

IB

Shortens phase 3 repolarization

IC

Slows phase 0 depolarization

II

Suppresses phase 4 depolarization

III

Prolongs phase 3 depolarization

IV

Shortens duration of action potential

For each class of antiarrhythmic agent, name several commonly used agents:

IA

Quinidine, amiodarone, procainamide, disopyramide

IB

MeLT: Mexilitine, Lidocaine, Tocainamide

IC

Flecainide, encainide, propafenone

II

Propranolol, esmolol, metoprolol, atenolol

III

Sotalol, ibutilide, bretylium, amiodarone

IV

Verapamil, diltiazem

For each subtype of class I antiarrhythmics, describe binding affinity for Na channels and the effect on APD

IA

Intermediate binding affinity to Na+ channels, also blocks K+ channels; prolongs AP duration

IB

Rapid rate of binding and release; shortens AP duration

IC

Tight binding and slow release; minimal change in AP duration

For each antiarrhythmic agent, name the unique toxicity/toxicities:

Quinidine

Cinchonism—headache, tinnitus, thrombocytopenia, torsades de pointes

Procainamide

Reversible drug-induced lupus

Lidocaine

CNS depression, cardiac depression, local anesthetic

Flecainide

Proarrhythmic

Propranolol

Sedation and fatigue, erectile dysfunction, exacerbation of asthma and COPD, masks effects of hypoglycemia

Bretylium

Severe postural hypotension

Amiodarone

Interstitial pulmonary fibrosis, thyroid dysfunction, hepatotoxicity, tremor, ataxia, neuropathy, bluish discoloration of skin, corneal deposits

What is the drug of choice for abolishing acute supraventricular tachycardia (SVT)?

Adenosine

Antihypertensives

For each of the following drugs, provide:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects and unique toxicity (TOX) (if any)

β-Blockers

MOA: P-blockade ↓ cAMP

IND: intravenous agent for the short-term management of HTN

TOX: impotence, asthma, mask signs of hypoglycemia, CV effects (bradycardia, CHF, AV block), sedation

Prazosin, terazosin, doxazosin

MOA: α-blocker

IND: essential HTN, benign prostatic hypertrophy

TOX: first-dose hypotension

Phentolamine

MOA: reversible a-blocker

IND: diagnosis of pheochromocytoma

Phenoxybenzamine

MOA: irreversible a-blocker

IND: diagnosis of pheochromocytoma

Nifedipine

MOA: dihydropyridine Ca2+ blockers, selective for vascular smooth muscle

IND: essential HTN

TOX: bradycardia, hypotension, metabolic acidosis

Diltiazem, verapamil

MOA: nondihydropyridine Ca2+ blockers, verapimil is cardioselective, diltiazem has intermediate affinity for heart and vascular smooth muscle

IND: essential HTN

TOX: mild LFT abnormality, sexual dysfunction

Clonidine

MOA: centrally acting α_2-agonist that decreases sympathetic outflow

IND: mild-to-moderate HTN

TOX: dry mouth, rebound hypotension with sudden withdrawal

α-Methyldopa

MOA: converted to α-methyl norepinephrine (NE) to act centrally as an a-agonist and decrease sympathetic outflow

IND: pregnant patients with HTN

TOX: positive Coombs test, drowsiness

Hydralazine

MOA: causes arteriolar vasodilation by increasing cGMP in vascular smooth muscle

IND: essential HTN

TOX: drug-induced lupus, angina

Minoxidil

MOA: causes arteriolar vasodilation by causing K+ channels to open on vascular smooth muscle hyperpolarizing the membrane and decreasing voltage-gated Ca2+ current

IND: HTN, alopecia

TOX: hypertrichosis, pericardial effusion

Nitroprusside

MOA: metabolism of nitroprusside releases NO which causes vasodilation via cGMP.

IND: malignant HTN.

TOX: cyanide toxicity (avoided if drug is mixed just prior to administration).

For each condition listed below, select the best antihypertensive agent(s):

Angina pectoris

β-Blockers, Ca2+ channel blockers

Diabetes

Angiotensin-converting enzyme inhibitors (ACEi), Ca2+ blockers, β-blockers

Hyperlipidemia

ACEi, Ca2+ blocker

SVT

β-Blockers

CHF

Diuretics, ACEi, β-blockers

History of MI

β-blockers, ACEi

Chronic renal failure

Diuretics, Ca2+ blockers

Anxiety

β-Blockers

Benign prostatic hyperplasia

α_1-Selective antagonist

Pheochromocytoma

Phenoxybenzamine, phentolamine

Hypertrophic obstructive cardiomyopathy

Phenoxybenzamine, phentolamine

Asthma, COPD

Diuretics, Ca2+ blockers

Hyperthyroidism

β-Blockers

Moderate bradycardia

β-Blockers with intrinsic sympathomimetic activity: pindolol and acebutol

Pregnancy

α-Methyldopa

Migraine headaches

β-Blockers

For each condition listed below, list the antihypertensive agent that should be avoided:

CHF

Verapamil

Asthma, COPD

β-Blockers

What class of diuretics is especially useful in black and elderly patients?

Thiazide diuretics

What class of diuretics is useful in patients who have not responded to thiazides?

Loop diuretics

What class of antihypertensives is useful in patients who cannot tolerate the side effects of ACEi?

Angiotensin receptor blockers (ARBs)

What classes of antihypertensive agents are absolutely contraindicated in pregnant patients?

ACEi and ARBs

List three agents useful in the management of malignant HTN:

1. Sodium nitroprusside

2. Hydralazine

3. Labetalol

Lipid-Lowering Agents

Cholestyramine

MOA: bile acid-binding resin, ↓ bile acid stores, ↑ catabolism of plasma LDL

IND: adjuvant therapy for patients with familial hypercholesterolemia, ↓ LDL

TOX: constipation, GI discomfort, may interfere with intestinal absorption of other drugs, LFT changes, myalgias

Statins

MOA: hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, rate-limiting step of XOL synthesis

IND: hypercholesterolemia: to ↓ LDL

TOX: hepatotoxicity, rhabdomyolysis

Niacin

MOA: reduces release of fatty acids from adipose; ↓ LDL synthesis in liver

IND: hypercholesterolemia: to ↑ HDL and ↓ LDL

TOX: flushing, pruritus (both reversible with aspirin), hepatotoxicity, GI upset, paresthesias

Gemfibrozil, clofibrate

MOA: stimulate lipoprotein lipase to increase catabolism of VLDL and triglycerides (↓ VLDL, ↓ TGs)

IND: hypercholesterolemia; dramatically ↓ TGs, ↑ HDL

TOX: myositis, hepatoxicity

Autonomics

Direct cholinergic agonists

ACh

MOA: physiologic cholinergic agonist

IND: no clinical use; ACh decreases heart rate, cardiac output, and blood pressure

TOX (for all direct cholinergic agonists):

1. Diarrhea

2. Diaphoresis

3. Miosis

4. Nausea

5. Urinary urgency

Bethanechol

MOA: binds primarily at muscarinic receptors; stimulates bowel and bladder smooth muscle contraction

IND: postoperative ileus and urinary retention

Pilocarpine

MOA: direct cholinergic agonist that activates ciliary muscle of the eye and pupillary sphincter

IND: glaucoma

Indirect cholinergic agonists (anticholinesterases)

Neostigmine, physostigmine

MOA: inhibitor of acetylcholinesterase → accumulation of ACh at synapses

IND: postoperative ileus, urinary retention, myasthenia gravis, reversal of neuromuscular blockade; atropine overdose (physostigmine)

TOX: generalized convulsions (rare)

Edrophonium, pyridostigmine

MOA: inhibitor of acetylcholinesterase

IND: diagnosis (edrophonium) and treatment (pyridostigmine) of myasthenia gravis

Echothiophate

MOA: irreversible inhibitor of acetylcholinesterase

IND: treatment of organophosphate overdose, galucoma

List the toxicities of acetylcholinesterase poisoning (caused by parathion or organophosphates):

“DUMBELS”

Diarrhea

Urination

Miosis

Bronchoconstriction

Excitation of skeletal muscles

Lacrimation

Sweating and Salivation

Atropine

MOA: nonselective muscarinic antagonist

IND: pupillary dilation, reduction of gastric acid secretion, reduction of GI motility, reduction of airway and salivatory secretions, organophosphate/cholinergic poisoning

TOX:”Dry as a bone, Red as a beet, Blind as a bat, Mad as a hatter, Hot as a hare.”

Dry as a bone: ↓ perspiration, lacrimation, salivation

Red as a beet: dry, red skin

Blind as a bat: blurry vision

Mad as a hatter: hallucinations, delirium

Hot as a hare: hyperthermia

Describe how atropine acts on the following organs or systems:

Eyes

Pupillary dilation (bella donna alkaloid), mydriasis, cycloplegia

Airways

Blocks bronchial secretion, bronchodilation

Salivary glands

Blocks salivary secretion

Heart

Bradycardia initially; tachycardia ultimately

Scopolamine

MOA: nonselective muscarinic antagonist

IND: motion sickness

Ipratropium

MOA: nonselective muscarinic antagonist

IND: bronchodilator used for asthma or COPD

Benztropine

MOA: centrally acting antimuscarinic agent

IND: adjuvant therapy for Parkinson disease

Hexamethonium

MOA: competitive nicotinic ganglion blocker

IND: used for HTN in the past

Succinylcholine

MOA: depolarizing neuromuscular blocker (nicotinic antagonist)

IND: neuromuscular blockade during general anesthesia

TOX: malignant hyperthermia when combined with halogenated anesthetic agents in susceptible patients (treat with dantrolene)

Tubocurarine, atracurium, vecuronium

MOA: nondepolarizing neuromuscular blocker

IND: neuromuscular blockade during general anesthesia; atracurium and vecuronium are degraded in the plasma and therefore preferred in patients with renal failure

TOX: may cause histamine release resulting in bronchospasm, skin wheals, and hypotension

Pralidoxime

MOA: cholinesterase regenerator

IND: used for organophosphate poisoning

State the MOA for each of the following agents:

Hemicholinium

Inhibits reuptake of choline in cholinergic neurons (rate-limiting step in ACh synthesis)

Botulinum

Inhibits release of ACh in cholinergic neurons

Reserpine

Inhibits VMAT transporter of dopamine into storage vesicles in adrenergic neurons

Guanethidine

Inhibits release of NE from adrenergic neurons

Amphetamine

Stimulates release of NE from adrenergic neurons (indirect-acting amines)

Cocaine, tricyclic antidepressants

Inhibit reuptake of NE from synapse

Direct adrenergic agonists

Epinephrine

MOA: agonist at αx, α_2, β_1, β_2 receptors

IND: acute, refractory asthma (bronchodilator), open angle glaucoma, anaphylactic shock, used with local anesthetic to ↑ duration of action (local vasoconstriction)

TOX: CNS disturbance, HTN, arrhythmia, pulmonary edema

Describe the effect of epinephrine on each of the following organs or tissues:

Myocardium

Positive inotropic and chronotropic effects (β_1)

Blood vessels

Overall ↑ blood pressure (vasoconstriction of cutaneous mucous membrane and visceral vasculature; vasodilation of liver and skeletal muscle vasculature) (α_1 > β_2)

Lungs

Bronchodilation (β_2)

Liver

Increased glycogenolysis, increased insulin release (β_2)

Adipose tissue

Increased lipolysis (α_2, β_1, β_2, β_3)

Pupils

Mydriasis (α_1 radial dilator muscle contraction); accommodation for far vision (β_2 ciliary muscle relaxation)

Skin

Piloerection(α_1)

Norepinephrine

MOA: Selective adrenergic agonist. Strong α-agonist that also stimulates β_1 receptors. NE produces only minimal stimulation of β_2 receptors.

IND: Useful in maintaining blood pressure in shock.

Compare the effects of NE and epinephrine (EPI) at the different adrenergic receptors.

α_1 EPI ≥ NE

α_2 EPI ≥ NE

β_1 EPI = NE

β_2 EPI >> NE *creates difference

Phenylephrine

MOA: direct adrenergic agonist; stimulates α_1 > α_2

IND: nasal decongestant

TOX: causes HTN

Clonidine

MOA: direct adrenergic agonist; stimulates α_2 > α_1

IND: HTN (especially in pregnant patients), nicotine, heroin, and cocaine withdrawal

TOX: rebound HTN, dry mouth, drowsiness

Isoproterenol

MOA: direct adrenergic agonist; stimulates β_1 and β_2 receptors equally

IND: Bronchodilator used in asthma

Dobutamine

MOA: direct adrenergic agonist; stimulates β_1 > β_2

IND: positive inotropic agent used to improve cardiac output in heart failure

Albuterol, terbutaline

MOA: direct adrenergic agonist; stimulates β_2 > β_1

IND: bronchodilator used in asthma; slows preterm labor by inhibiting uterine contraction (terbutaline)

TOX: tremor, tachycardia

Dopamine

MOA: direct adrenergic agonist; stimulates D_1 and D_2 receptors equally

IND: maintenance of blood pressure in shock

What is the toxicity of most adrenergic agonists?

1. CNS disturbance—fear, anxiety, tension, headache

2. HTN

3. Arrhythmias

4. Pulmonary edema

Indirect adrenergic agonists

Amphetamine

MOA: stimulates release of NE from adrenergic neurons

IND: attention deficit hyperactivity disorder, narcolepsy, appetite control

TOX: psychosis, anxiety

Tyramine

MOA: stimulates release of NE from adrenergic neurons

IND: no clinical indications; found in fermented foods

TOX: severe vasopressor effects in combination with MAOIs

Ephedrine

MOA: stimulates release of NE from synaptic vesicles in adrenergic neurons

IND: nasal decongestant, enhances athletic performance

TOX: causes HTN

Cocaine

MOA: inhibition of catecholamine reuptake

IND: local anesthetic

TOX: arrhythmias, MI, seizures

Adrenergic antagonists

Phenoxybenzamine

MOA: irreversible adrenergic antagonist; blocks α_1 > α_2

IND: HTN 2° to pheochromocytoma

TOX: nasal congestion, postural hypotension, compensatory tachycardia

Phentolamine

MOA: reversible adrenergic antagonist; blocks α_1 and α_2 receptors equally

IND: diagnosis of pheochromocytoma; management of intraoperative HTN

Prazosin, terazosin

MOA: adrenergic antagonist; selectively blocks α_1 receptors

IND: treatment of HTN and benign prostatic hypertrophy

TOX: orthostatic hypotension

Propranolol

MOA: adrenergic antagonist, blocks both P_1 and P_2 receptors

IND: HTN, angina prophylaxis, antiarrhythmic, anxiety, thyroid storm, migraine prophylaxis

TOX: bronchoconstriction, arrhythmias, sexual dysfunction, CNS sedation, and fatigue

Describe the effect of propranolol on each of the following tissues:

Heart

Decreased cardiac output

Blood vessels

Reflex peripheral vasoconstriction

Kidneys

Increased Na+ retention

Lungs

Bronchoconstriction

Metoprolol, atenolol, esmolol

MOA: adrenergic antagonist; selectively blocks P_1 receptors

IND: HTN, angina prophylaxis, MI, superventricular tachycardia (esmolol)

TOX: Hypotension, bradycardia, hyperglycemia, ventricular dysrhythmias

List two β-blockers with intrinsic sympathomimetic activity:

1. Acebutolol

2. Pindolol

Which β-blocker also blocks α_1receptors?

Labetalol

What are the six common side effects of β-blockers?

1. Bronchoconstriction/asthma attack

2. Arrhythmia

3. Sexual dysfunction

4. Fasting hypoglycemia, masking of hypoglycemic signs

5. CNS sedation, fatigue

6. Hypotension

Describe the effect of dopamine on each of the following organs or tissues:

Myocardium

Positive inotropic and chronotropic effects

Blood vessels

Vasoconstriction →↑ BP

Kidneys

Increases renal blood flow at low and moderate doses

CHAPTER 6

Pulmonary

EMBRYOLOGY

From what structure does the lung bud arise?

Foregut

From which embryonic layer is the lining of the respiratory tract derived?

Endoderm

From which embryonic layer is the muscle and connective tissue of the respiratory tract derived?

Mesoderm

What is the consequence of incomplete separation of the lung bud from the esophagus?

Tracheoesophageal fistula (TEF)

What is the most typical type of TEF?

Esophageal atresia (ends in blind pouch)

What other constellation of developmental abnormalities should you look for with TEF?

VATER syndrome: V ertebral, A nal, T racheal, E sophageal, R adial/R enal

At what gestational age is a human capable of respiration?

25 weeks

In what period do the majority of alveoli develop?

Postpartum

What histology is typical of cells lining the conducting airway?

Pseudocolumnar ciliated cells

Which cells produce surfactant?

Type II pneumocytes

List the structures the diaphragm is derived from:

“Several Parts Build Diaphragm”— Septum transversum, Pleuroperitoneal folds, Body wall, Dorsal mesentery of esophagus

Which disorder results from abnormal development of the diaphragm?

Diaphragmatic or hiatal hernia

Where can pain from the diaphragm refer?

To the shoulder

ANATOMY

Which nerve provides motor innervation to the diaphragm?

Phrenic nerve (“C3, C4, C5 keep the diaphragm alive”)

Which muscles are involved in respiration?

Diaphragm (most important), external intercostals, sternocleidomastoids, anterior and medial scalene

What area of the left lung is most similar to the right middle lobe?

Lingula (technically part of the left upper lobe)

Which lobe does foreign body aspiration most commonly affect when supine?

Superior segment of right lower lobe (because right main stem bronchus is wider, more vertical, and the superior segment ostium is posteriorly located)

The bifurcation of the trachea occurs at the level of which vertebral body?

Intervertebral disk T4 to T5

What four structures make up a bronchopulmonary segment?

1. Segmental bronchus

2. Branch of the pulmonary artery

3. Branch of the bronchial artery

4. Tributaries of the pulmonary vein

Which syndrome can result from a malignant tumor in the region of the superior pulmonary sulcus?

Pancoast syndrome (lower trunk brachial plexopathy and Horner syndrome)

PHYSIOLOGY

Lung Volumes and Capacities

Name the lung volume defined below:

Expired volume with each normal breath

Tidal volume (TV)

Volume that can be inspired beyond the TV

Inspiratory reserve volume (IRV)

Volume that can be expired beyond the TV

Expiratory reserve volume (ERV)

Volume that remains in the lungs after maximal expiration

Residual volume (RV)

Name the lung capacity defined below:

TV + IRV

Inspiratory capacity (IC)

ERV + RV

Functional residual capacity (FRC)

TV + IRV + ERV

Vital capacity (VC)

Volume which can be forcibly expired in 1 second after maximal inspiration

Forced expiratory volume (FEV_1)

Total volume which can be forcibly expired

Forced VC (FVC)

TV + IRV + ERV + RV

Total lung capacity (TLC)

What is the formula for minute ventilation?

TV × respiratory rate (breaths per minute)

Lung Compliance and Resistance

What is the relationship between compliance and elasticity?

Compliance and elasticity are inversely related.

Name four common causes of decreased lung compliance:

1. Pulmonary fibrosis

2. Atelectasis

3. Acute respiratory distress syndrome

4. Neonatal respiratory distress syndrome

What is a common smoking-related cause of increased lung compliance?

Emphysema, normal aging lungs

What is the effect of surfactant on alveolar surface tension and lung compliance?

Surfactant decreases surface tension to allow small alveoli to stay open and increases compliance.

What is the law of Laplace?

Pressure = 2 × surface tension/radius. The larger the radius of the vessel/airway, the more stable and less likely it is to collapse.

What is the relationship between airflow and resistance?

Airflow is inversely proportional to airway resistance.

What is the relationship between airway radius and resistance?

Resistance is inversely proportional to the fourth power of the radius (Poiseuille law).

For each factor below, state whether airway resistance will be increased or decreased:

Bronchoconstriction

Increased

Parasympathetic stimulation

Increased

Sympathetic stimulation

Decreased

High lung volumes

Decreased

Low lung volumes

Increased

Hemoglobin

For each of the factors below, determine whether the hemoglobin dissociation curve will be shifted to the left or to the right?

Increased PCO_2

Right

Increased pH

Left

Decreased temperature

Left

Increased 2,3-bisphosphoglycerate (2,3-BPG) concentration

Right

Fetal hemoglobin

Left

carbon monoxide poisoning

Left

Note: ↑ in any factor (except pH) results in right shift.

What is the mnemonic for right shift?

CADET face RIGHT (C O_2, Acid/Altitude, D PG (2,3-D PG), E xercise, T emperature

Which quaternary conformation of Hb has the highest affinity for oxygen?

The R (relaxed form)

How does hemoglobin’s affinity for O_2compare to that of cO?

The affinity of CO is 200 times as great as that of O_2.

What are the signs and symptoms of carbon monoxide toxicity?

Headache, nausea/vomiting, loss of consciousness, confusion

What are the three ways in which cO_2 is transported from the tissues to the lungs?

1. As HCO_3- in erythrocytes

2. Bound to hemoglobin (carbaminohemoglobin)

3. Dissolved in blood

Which enzyme catalyzes the conversion of CO_2 into HCO_3-?

Carbonic anhydrase

Which protein is the main buffer within erythrocytes?

Deoxyhemoglobin

Acclimatization to High Altitude

For each of the values below, determine how they are affected by high altitude acutely:

Ventilation

Increased

PAO2, PaO_2

Decreased (due to decreased partial pressure of atmospheric O_2)

PACO2, PacO_2

Decreased (due to hyperventilation)

Systemic arterial pH

Increased

Hemoglobin saturation

Decreased

Hemoglobin concentration

No change

For each of the values below, determine how they are affected by high altitude chronically:

Ventilation

Increased

PAO_2, PaO_2

Decreased (due to decreased partial pressure of atmospheric O_2)

PACO_2, PaCO_2

Decreased (due to hyperventilation)

Systemic arterial pH

Increased (but closer to normal due to renal excretion of bicarbonate)

Hemoglobin saturation

Decreased

Hemoglobin concentration

Increased (polycythemia due to increased erythropoietin production)

Lung Zones

Choose the zone or region of the lungs that fits each description below:

Alveolar pressure > arterial pressure > venous pressure

Zone 1

Arterial pressure > alveolar pressure > venous pressure

Zone 2

Arterial pressure > venous pressure > alveolar pressure

Zone 3

V/Q ≈ 3 → wasted ventilation

Apex

V/Q ≈ 0.6 → wasted perfusion

Base

What is the effect of hypoxia on pulmonary blood vessels?

Vasoconstriction. Note: hypoxia causes vasodilation in all other vascular beds.

What is the quotient of V/Q in a lung where the pulmonary artery is completely occluded (shunt-unventilated blood)?

0

What is the quotient of V/Q in complete airway obstruction (physiologic dead space)?

∞

Neurologic Regulation of Respiration

Describe the function of each of the following neural structures in the control of respiration:

Medullary respiratory center

Determines the rhythm of breathing by controlling inspiration and expiration

Pontine apneustic center

Stimulates inspiration

Cerebral cortex

Voluntary control of respiration

Lung stretch receptors in bronchial smooth muscle

Reflexive slowing of respiratory frequency (Hering-Breuer reflex)

Irritant receptors in airway epithelial cells

Initiate coughing

Juxtacapillary (J) receptors in alveolar walls

Cause rapid shallow breathing in congestive heart failure

Joint and muscle receptors

Stimulate respiration at the initiation of exercise

Medullary chemoreceptors

Increase breathing rate in response to low pH

Peripheral chemoreceptors in the carotid and aortic bodies

Increase breathing rate in response to low arterial PO_2, low pH, and high PCO_2

PATHOLOGY

Pulmonary Edema, ARDS, and Neonatal RDS

Which syndrome is characterized by diffuse alveolar damage, pulmonary edema, and respiratory failure?

Adult respiratory distress syndrome (ARDS)

What type of material is seen in the alveoli of a patient in the acute phase of ARDS?

Hyaline membranes formed by a fibrinous exudate and necrotic cellular debris

What are some of the causes of ARDS?

Shock of any etiology, fat embolism, gram-negative sepsis, severe bacteria/viral infections, near-drowning, aspiration of GI contents, acute pancreatitis, heroin overdose, oxygen toxicity, cytotoxic drugs

What is the most common cause of respiratory failure in the newborn and also of death in premature infants 28 weeks gestational age?

Neonatal respiratory distress syndrome (hyaline membrane disease)

What is the typical clinical presentation of neonatal respiratory distress syndrome?

Preterm infants with initially normal respirations followed by cyanosis, tachypnea, and signs of respiratory distress

What is the pathogenesis of neonatal respiratory distress syndrome?

Deficiency of pulmonary surfactant leading to increased surface tension

What type of cells produce pulmonary surfactant?

Type II pneumocytes

What is the predominant chemical in pulmonary surfactant?

Dipalmitoyl phosphatidylcholine (lecithin)

What is the diagnostic test of choice to judge fetal lung maturity?

Amniotic fluid lecithin: sphingomyelin ratio (a ratio of 2:1 implies adequate surfactant is present)

What are the three strongest risk factors for neonatal respiratory distress syndrome?

1. Prematurity

2. Maternal diabetes

3. Delivery by caesarean section

What is the classic pathologic finding in the alveoli of an infant with neonatal respiratory distress syndrome?

Intra-alveolar hyaline membranes

Infants surviving an initial bout of neonatal respiratory distress syndrome are at risk for which five complications?

1. Bronchopulmonary dysplasia (resulting in part from oxygen therapy)

2. Retinopathy of prematurity (resulting from oxygen therapy)

3. Patent ductus arteriosus

4. Intraventricular cerebral hemorrhage

5. Necrotizing enterocolitis

What medications can you give to prevent neonatal respiratory distress syndrome?

Glucocorticoids given to the mother can accelerate fetal lung maturation and reduce the risk of neonatal respiratory distress syndrome.

Pulmonary Embolism

What are the most common clinical presentations of PE?

Tachycardia, tachypnea, dyspnea, pleuritic chest pain, or hemoptysis

What is the etiology of 95% of pulmonary emboli?

Dislodged deep venous thromboses (DVT) from the deep veins of the thigh or pelvis

What factors favor the development of a DVT?

Virchow triad: (1) stasis, (2) hypercoagulability, (3) endothelial damage

How do you diagnose a PE radiographically?

V/Q scan or CT angiogram (1st line), pulmonary angiography (gold standard)

What type of tumors commonly cause a DVT by inducing a hypercoagulable state?

Adenocarcinomas

What is the most common genetic disease that predisposes to the development of DVT?

Factor V Leiden

What type of embolism can develop uniquely in a peripartum woman?

Amniotic fluid embolism

For what type of embolism is a patient with a long bone fracture at risk?

Fat emboli from bone marrow, pulmonary thromboembilsm due to trauma and stasis

What type of infarction results from a PE?

Hemorrhagic infarction (appears as wedge-shaped opacity on chest x-ray [CXR])

What therapy is indicated for high-risk patients during the workup of PE and for patients diagnosed with PE?

Full treatment doses of heparin (unfractionated or low molecular weight)

What is used for long-term prophylaxis for patients at risk of developing DVT?

Warfarin

What is an alternative to warfarin for outpatient DVT prophylaxis?

Subcutaneous heparin (low molecular weight or unfractionated)

Obstructive Lung Disease

What are the most common disease categories causing pulmonary hypertension?

1. Chronic obstructive pulmonary disease (COPD)

2. Left-sided heart disease

3. Recurrent PE

4. Autoimmune disorders

How is the heart affected by long-standing pulmonary hypertension?

Pulmonary hypertension causes right ventricular hypertrophy and dilatation.

What is the reversal of a left-to-right shunt to a right-to-left shunt due to long-standing pulmonary hypertension?

Eisenmenger syndrome

What is the most common cause of COPD?

Cigarette smoking

What is the effect of COPD on hematocrit (Hct)?

Chronic hypoxia leads →↑ Hct

What is the effect of COPD on FEV_1/FVC?

↓ FEV_1/FVC 0.8

Name the obstructive pulmonary disorder described by the following pathologic features:

Smooth muscle and goblet cell hyperplasia; mucus-plugged airways containing Curschmann spirals, eosinophils, and Charcot-Leyden crystals

Bronchial asthma

Hyperplasia of bronchial submucosal glands, hypersecretion of mucus, squamous metaplasia or dysplasia of bronchial epithelium

Chronic bronchitis

Permanent airway dilation and scarring; inflammation and necrosis of bronchial walls and alveolar fibrosis

Bronchiectasis

Alveolar enlargement due to alveolar wall destruction; ↓ lung elasticity

Pulmonary emphysema

Diagnosed clinically by productive cough for > 3 consecutive months for 2+ years

Chronic bronchitis

Name the chronic disorder characterized by increased airway reactivity, resulting in paroxysmal bronchial contraction:

Bronchial asthma

Name the two types of bronchial asthma:

1. Atopic or immune asthma

2. Nonatopic or nonimmune asthma

What type of hypersensitivity response is seen in atopic asthma?

Type I hypersensitivity response mediated by IgE and mast cells, eosinophils, and basophils

What other conditions are typically seen in association with atopic asthma?

Allergic rhinitis, eczema

Name several common triggers of atopic asthma:

Dust, pollen, food, and animal dander

Name several triggers of nonatopic asthma:

Respiratory tract infection, cold, chemical irritants, exercise

What are the two common presenting features of bronchial asthma?

1. Dyspnea

2. Wheezing

Which four conditions are commonly associated with bronchiectasis?

1. Bronchial obstruction from tumor or foreign body

2. Cystic fibrosis (CF)

3. Kartagener syndrome

4. Necrotizing pneumonia

What are the three common presenting features of bronchiectasis?

1. Abundant, copious, often foul-smelling sputum

2. Chronic cough

3. Hemoptysis

What are the components of an acinus of the lungs?

Alveoli, air ducts, respiratory bronchioles, terminal bronchioles

Name the type of emphysema described below:

Enlargement of bronchioles, typically in the upper lobes and apices (most often associated with smoking)

Centriacinar emphysema

Destruction and dilation of entire acinus, typically in the lower lobes; associated with (α_1antitrypsin deficiency

Panacinar emphysema

Destruction of the distal acinus occurring typically near the pleura and areas of fibrosis that may cause pneumothorax

Paraseptal emphysema

Irregular involvement of the acinus that may be related to inflammatory processes of the lungs

Irregular emphysema

How does smoking cause emphysema?

Smoke particles recruit inflammatory cells, promote the release and enhance the activity of elastase, and inhibit the activity of α_1-antitrypsin.

What is the role of (α_1antitrypsin deficiency in the development of emphysema?

The lack of this protease inhibitor results in the digestion of the elastin in alveolar walls by elastase.

What is the effect of emphysema on the anteroposterior diameter of the chest and the TLC?

Both are increased.

Restrictive Lung Disease

What general category of pulmonary disease is characterized by dyspnea, decreased lung volumes, and decreased compliance?

Restrictive lung disease

What is the effect of restrictive lung disease on FEV_1/FVC?

↓ FEV_1/FVC≥ 0.8

What are the two categories of restrictive lung disease?

1. Pulmonary: interstitial lung disease or pneumonitis, resulting in poor lung expansion

2. Extrapulmonary: extrapulmonary disease associated with disorders of the chest wall, pleura, or respiratory muscles

What are the common causes of pulmonary restrictive lung disease?

Idiopathic, connective tissue disease, drug-related, sarcoidosis (all → poor lung expansion)

What are the common causes of extrapulmonary restrictive lung disease?

Neuromuscular disease (polio), obesity, pleural disease, and scoliosis (all → poor breathing mechanics)

Name the specific type of restrictive lung disease described below:

65-year-old (y/o) hay farmer with recent exposure to moldy hay presents with chronic dry cough, chest tightness; physical examination (PE): bilateral diffuse rales; bronchoscopy: interstitial inflammation; bronchioalveolar lavage: lymphocyte and mast cell predominance

Hypersensitivity pneumonitis

35-y/o man presents with intermittent hemoptysis and hematuria; W/U demonstrates alveolar hemorrhage and acute glomerulonephritis

Goodpasture syndrome

40-y/o with progressive hypoxemia and cor pulmonale; lung biopsy demonstrates chronic inflammation of the alveolar wall in a pattern consistent with honeycomb lung; bronchioalveolar lavage: mild eosinophilia

Idiopathic pulmonary fibrosis

58-y/o former shipbuilder presents with the insidious onset of dyspnea; transbronchial biopsy demonstrates interstitial pulmonary fibrosis, ferruginous bodies; chest CT scan demonstrates pleural effusion and dense pleural fibrocalcific plaques

Asbestosis

55-y/o miner (nonsmoker) presents with dyspnea and dry cough; pulmonary function tests (PFTs) show both obstructive and restrictive pattern; chest x-ray (CXR): hilar lymphadenopathy with eggshell calcifications

Silicosis

60-y/o male with 100 pack-year history of (h/o) smoking presents with pleuritic chest pain, hemoptysis, and dyspnea; PE: dullness to percussion and absent breath sounds in the right lower lung field

Pleural effusion (secondary to malignancy)

50-y/o former heavy smoker presents with multiple lung and rib lesions; biopsy: cells (similar to the Langerhans cells of the skin) containing tennis racket-shaped Birbeck granules

Eosinophilic granuloma

30-y/o black female presents with DOE, fever, arthralgia; PE: iritis, erythema nodosum; W/U: eosinophilia, ↑ serum ACE levels; PFT: restrictive pattern; CXR: bilateral hilar lymphadenopathy interstitial infiltrates; lymph node biopsy: noncaseating granulomas

Sarcoidosis

Which typically asymptomatic disorder causes visible black deposits in the lungs of coal workers?

Anthracosis

Which three medications are known to commonly cause interstitial lung disease?

Bleomycin, methotrexate, and amiodarone

Pulmonary Infections

What infection is characterized by fever > 39°C, chills, cough productive of blood-tinged, purulent sputum, pleuritic pain, hypoxia, and lobar infiltrate on CXR?

Acute pneumonia

What infection is characterized by fever 39°C, nonproductive cough, GI upset, and diffuse patchy infiltrates on CXR?

Atypical pneumonia

Name the most common organism(s) associated with the pulmonary infection described below:

Community-acquired acute pneumonia

Streptococcus pneumoniae

Commonly follow a viral respiratory infection

Staphylococcus aureus and Haemophilus influenzae

Interstitial pneumonia

Mycoplasma pneumoniae (most common), Chlamydia pneumoniae

Fungal pneumonia in an AIDS patient

Pneumocystis jiroveci (previously Pneumocystis carinii)

Typical pneumonia in neonate

Streptococcus agalactiae (group B streptococcus)

Typical pneumonia in an alcoholic after aspiration

Klebsiella pneumoniae

Atypical pneumonia in patient with positive cold agglutinin test

Mycoplasma pneumoniae

Atypical pneumonia in a neonate with trachoma

Chlamydia trachomatis

Atypical pneumonia in a dairy worker

Coxiella burnetti

Atypical pneumonia in a rabbit hunter

Francisella tularensis

Pneumonia in a bird owner with splenomegaly and bradycardia

Chlamydia psittaci

Hospitalized patient with lobar pneumonia

Streptococcus pneumoniae> S. aureus

Pneumonia in an IV drug user

Streptococcus pneumoniae, K. pneumoniae, and S. aureus

Pneumonia in a patient recovering from viral upper respiratory infection

Staphylococcus aureus, H. influenzae

Atypical pneumonia in a spelunker from the Ohio river valley

Histoplasma capsulatum

Atypical pneumonia in a patient from the southwestern United States

Coccidioides immitis

Associated with spread by inhalation of contaminated water droplets from air conditioners

Legionella pneumophila

Name the most common causative pathogen(s) of pneumonia for each age group below:

Neonates

Group B streptococci, Escherichia coli, Listeria

Children (6 weeks-18 years)

RSV and other viruses, M. pneumoniae, C. pneumoniae, S. pneumoniae

Adults (18-40 years old)

Mycoplasma pneumoniae, C. pneumoniae, S. pneumoniae

Adults (45-65 years old)

Streptococcus pneumoniae, H. influenzae, anaerobes, viruses, M. pneumoniae

Adults (> 65 years old)

Streptococcus pneumoniae, viruses, anaerobes, H. influenzae, gram-negative rods

Name four common complications of lobar pneumonia:

1. Abscess formation (especially S. aureus and anaerobes)

2. Empyema or spread of infection to the pleural cavity

3. Organization of exudate to form scar tissue

4. Sepsis

What type of pulmonary infection is characterized by localized suppurative necrosis of lung tissue?

Lung abscess

Name several bacterial pathogens capable of causing lung abscess:

Staphylococcus aureus, aerobic and anaerobic streptococci, gram-negative bacilli, and anaerobic oral flora

Cystic Fibrosis

What is the most common lethal genetic disease in Caucasians?

CF

What is the mode of inheritance of CF?

Autosomal recessive (chromosome 7)

Which membrane protein is defective in CF?

The cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel protein

What is the function of CFTR?

Regulation of sodium, chloride, and bicarbonate transport across the plasma membrane

What is the most common genetic lesion causing CF?

Deletion of three nucleotides encoding phenylalanine 508 in the CFTR; AF508 prevents the normal expression of CFTR

Describe how the ΔF508 mutation prevents normal expression of CFTR:

Altered membrane folding precludes glycosylation and transport to the plasma membrane.

What is the end result of the ΔF508 mutation of the CFTR gene?

Complete loss of CFTR in the plasma membrane

How does a defect in the CFTR affect exocrine glands?

Altered CFTR activity causes the accumulation of hyperviscid mucus that blocks the secretions of exocrine glands.

What tests are used to diagnose CF in infants?

Sweat chloride test, measurement of nasal potential difference, genotyping (definitive)

How does CF typically present in an infant?

Failure to thrive, meconium ileus, mother complains child “tastes salty”

Describe the effect of CF on each of the following organs:

Lungs

Recurrent pulmonary infections, bronchiesctasis; ↑ RV and TLC in chronic disease; ↓ FEV_1/FVC in acute exacerbation; pulmonary hemorrhage may occur

Pancreas

Variable defects in pancreatic exocrine function; may cause pancreatic insufficiency and diabetes mellitus

Intestines

Mucus plugs → small bowel obstruction; meconium ileus in some infants

Liver

Plugging of bile cannaliculi → cirrhosis

Epididymis and ductus deferens

Bilateral absence of the vas deferens

Salivary glands

Ductal dilation; squamous metaplasia of ductal epithelium and glandular atrophy

Which organisms are commonly responsible for pulmonary infections in CF?

Pseudomonas aeruginosa, S. aureus, and Pseudomonas cepacia

What is a common nutritional deficiency in CF?

Deficiency of the fat-soluble vitamins (vitamins A, D, E, and K)

What type of heart disease is common in patients with CF?

Cor pulmonale

Lung Cancer

What is the most common cause of cancer deaths in the United States for both men and women?

Lung cancer

What is the most common type of malignant tumor in the lungs?

Metastasis

What are the most common primary lung tumors?

Adenocarcinoma is slightly more common than squamous cell carcinoma

Name the type(s) of primary lung cancer associated with the following features:

Central location

Squamous cell and small (oat) cell carcinomas

Peripheral location

Adenocarcinoma, large cell carcinoma, bronchioalveolar carcinoma

Dysplasia and carcinoma in situ precede development of this tumor

Squamous cell carcinoma

Strongest link to smoking

Squamous cell and small (oat) cell carcinomas

Least linked to smoking, frequently seen in nonsmoking women

Bronchioalveolar carcinoma

Most aggressive tumor

Small (oat) cell carcinoma

Associated with production of PTH-related peptide, hypercalcemia

Squamous cell carcinoma

Associated with production of ADH (SIADH) and ACTH (Cushing syndrome)

Small (oat) cell carcinoma

Carcinoembryonic antigen (CEA) positive

Adenocarcinoma

Secretion of 5-hydroxytryptamine (5-HT, serotonin)

Carcinoid

Oat-like, dark blue cells

Small (oat) cell carcinoma

Tumor cells lining alveolar walls

Bronchioalveolar adenocarcinoma

Giant pleomorphic cells, poor prognosis, and high likelihood of cerebral metastasis

Large cell carcinoma

Tumor at apex of lung causes Horner syndrome or lower brachial plexopathy

Pancoast tumor

Rare pleural tumor is found in patients with a h/o exposure to asbestos

Malignant mesothelioma

Most common cancer in patients with h/o exposure to asbestos

Lung cancer

OTHER PATHOLOGY

Immotile cilia secondary to a dynein arm defect, associated with situs inversus, infertility, bronchiectasis

Kartagener syndrome

Causes stridor, toxic presentation, may be life threatening, thumbprint sign on x-ray, caused by H. influenzae

Acute epiglotittis

Causes stridor, nontoxic presentation, steeple sign on x-ray, caused by parainfluenza virus

Laryngotracheobronchitis, croup

PHARMACOLOGY

For each of the following drugs, provide:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects and unique toxicity (TOX) (if any)

Albuterol

MOA: β_2-agonist → bronchodilator, short acting

IND: asthma

TOX: tachycardia, arrhythmias, tremor, hyperglycemia

Inhaled corticosteroids (beclomethasone, fluticasone, triamcinolone)

MOA: anti-inflammatory; inhibits smooth muscle hyperreactivity

IND: moderate-to-severe asthma

TOX: oropharyngeal thrush, dysphonia

Cromolyn

MOA: anti-inflammatory; inhibits histamine release from mast cells

IND: prophylaxis for asthmatic attack

TOX: laryngeal edema (very rare)

Ipratropium

MOA: bronchodilator; cholinergic antagonist

IND: COPD.

TOX: Rare—minor systemic manifestations of anticholinergic effect

Leukotriene inhibitors (zileuton, zafirlukast, montelukast)

MOA: inhibits leukotriene synthesis (zileuton) or blocks leukotriene receptors (zafirlukast, montelukast)

IND: prophylaxis for asthmatic attack

TOX: elevation of liver enzymes

Theophylline

MOA: bronchodilator; exact mechanism unknown

IND: asthma

TOX: seizures and arrhythmias Inhaled albuterol as needed

What is the drug of choice for mild asthma?

Inhaled albuterol as needed

Which three classes of bronchodilators are useful in the management of asthma and COPD?

1. Anticholinergic agents (eg, ipratropium)

2. β-Agonists (eg, albuterol)

3. Theophylline (much less useful)

What is the drug of choice in an asthmatic requiring daily albuterol use?

Inhaled glucocorticoids

Describe how glucocorticoids act on airways to control asthma:

Glucocorticoids reduce inflammation and decrease the reactivity of airways to irritants such as cold, cigarette smoke, allergens, and exercise.

What type of therapy may be required in patients with daily asthma attacks?

Systemic steroid therapy; usually with oral prednisone or IV methylprednisolone

Name three agents used in the treatment of allergic rhinitis:

1. Antihistamines (eg, diphenhydramine, loratadine, terfenadine)

2. α-Agonist aerosols (eg, phenylephrine)

3. Corticosteroid nasal sprays (eg, beclomethasone, fluticasone, triamcinolone)

Which class of bronchodilators is useful in patients who cannot tolerate β-agonists?

Anticholinergic agents (eg, ipratropium)

CHAPTER 7

Gastroenterology

EMBRYOLOGY

What portion of the GI tract is derived from the embryonic foregut?

From the intra-abdominal esophagus → pancreas (distal to sphincter of Oddi)

What portion of the GI tract is derived from the embryonic midgut?

From the second part of the duodenum → proximal two-thirds of the colon (at the splenic flexure)

What portion of the GI tract is derived from the embryonic hindgut?

From the distal one-third of the colon → rectum (proximal to the pectinate line)

What GI structures are derived from the embryonic ectoderm?

Oropharynx (anterior two-thirds of tongue, lips, parotids, tooth enamel), anus, and rectum (distal to the pectinate line)

Name the embryonic layer supplied by the following arteries:

Celiac trunk

Foregut

Inferior mesenteric artery

Hindgut

Superior mesenteric artery

Midgut

What embryonic structure gives rise to the anterior two-thirds of the tongue?

First branchial arch

What embryonic structure gives rise to the posterior one-third of the tongue?

Third and fourth branchial arches

What disorder results from failure of fusion of the maxillary and medial nasal processes?

Cleft lip

What disorder results from failure of fusion of the nasal septum, lateral palatine processes, and/or median palatine process?

Cleft palate

What is Meckel diverticulum?

Persistence of the vitelline duct or yolk stalk that may contain ectopic tissue. Remember: “The rule of 2’s”: 2 in long, 2% of population, 2 ft from ileocecal valve, presents within 2 years of life, can contain 2 types of epithelia (gastric, pancreatic).

What primordial embryonic structures give rise to the pancreas?

Ventral bud → pancreatic head, uncinate process, main duct

Dorsal bud → everything else (body, tail, isthmus, accessory duct)

What congenital defect is caused by abnormal fusion of the ventral and dorsal buds of the pancreas?

Annular pancreas (leads to ring around duodenum and obstruction)

What congenital defect results from failure of migration of neural crest cells, causing an absence of parasympathetic ganglion cells in the distal colon?

Hirschsprung (congenital aganglionic) megacolon

What congenital defect results from incomplete canalization of the bile ducts during development and presents shortly after birth with clay-colored stools and jaundice?

Biliary atresia

ANATOMY

What are the four main layers of the wall of the digestive tract?

1. Mucosa

2. Submucosa

3. Muscularis

4. Serosa

Name the enteric plexus associated with the following descriptions:

Located between mucosa and inner layer of smooth muscle in GI tract wall

Submucosal (Meissner) plexus

Located between inner (circular) and outer (longitudinal) layer of smooth muscle in GI tract wall

Myenteric (Auerbach) plexus

Coordinates motility along the entire gut wall

Myenteric plexus = Motility

Controls local secretions, absorption, and blood flow

Submucosal plexus = Secretions

Name the lymphoid tissue found in lamina propria and submucosa of small intestine:

Peyer patches

What is the major function of the Peyer patch?

Detect antigens → secrete IgA into lumen

In the liver, which zone of the portal acinus contains the highest O_2concentration and nutrients?

Zone 1

Which zone of the portal acinus contains the lowest O_2 concentration and nutrients?

Zone 3

Name the three major branches of the abdominal aorta and their approximate vertebral level:

1. Celiac trunk (T12)

2. Superior mesenteric artery (L1)

3. Inferior mesenteric artery (L3)

What structure provides collateral venous drainage to the superior vena cava (SVC) when there is obstruction of the inferior vena cava (IVC)?

Azygous vein

Name the four key sites for portal-systemic shunt and the veins involved:

1. Esophagus (left gastric → esophageal)

2. Umbilicus (paraumbilical → superficial/inferior epigastric)

3. Rectum (superior rectal → middle/inferior rectal)

4. Posterior abdominal wall (colic → lumbar)

Which two vessels merge to form the portal vein?

Splenic (inferior mesenteric vein has already joined the splenic vein) and superior mesenteric veins

What important neural structure traverses the parotid gland?

Facial nerve (CN VII)

Which syndromes may result from reinnervation of the CN VII after Bell palsy or surgical severance of nerve?

Frey syndrome (sweating occurs along with salivation), crocodile tears syndrome (tearing occurs along with salivation)

What are the muscles of mastication?

Three open: masseter, temporalis, and medial pterygoid; one close: lateral pterygoid

What types of muscle are found in the esophagus?

Proximal one-third = skeletal; distal one-third = smooth; middle one-third = both

What is the function of the pylorus?

Acts as muscular sphincter to regulate movement of food out of the stomach and prevents reflux of duodenal contents

Which blood vessel lies posterior to the first part of the duodenum?

Gastroduodenal artery (a concern in cases of posterior perforation due to ulcers)

The common bile duct and main pancreatic duct empty into what portion of the duodenum?

Second (descending) part

The common bile duct and pancreatic duct drain into the duodenum through what structure?

Hepatopancreatic ampulla (of Vater)

What structure controls the release of bile into the duodenum?

Sphincter of Oddi

Which two ducts combine to form the common bile duct?

1. Common hepatic

2. Cystic duct

What structures make up the porta hepatis?

Hepatic artery, portal vein, common bile duct

What structure keeps the cystic duct open at all times for bile to flow freely in both directions?

Spiral valve (of Heister)

What is the “bare area” of the liver?

A portion of the diaphragmatic surface of the liver that is devoid of peritoneum

What divides the left and right lobes of the liver?

Interlobar fissure (an invisible line running from the gallbladder to the IVC)

What structure supports the duodenum at the duodenojejunal flexure?

Suspensory ligament (of Treitz)

Name the intestinal structures (duodenum, ileum, jejunum, or colon) associated with each of the following characteristics:

Long, finger-shaped villi

Jejunum

Intestinal glands (crypts) and 3 cm luminal diameter

Ileum

No villi, large crypts, and 6 to 9 cm luminal diameter

Colon

Large, numerous, plicae circularis

Jejunum

Accounts for the terminal three-fifths of the small intestine

Ileum

Contains fatty tags (appendices epiploicae)

Colon

Contains prominent Peyer patches

Ileum

Contains long vasa recta

Jejunum

What term is used to describe the three longitudinal bands of smooth muscle in the colon?

Teniae coli

What is the name for the wall sacculations in the colon that are separated by the plicae semilunaries?

Haustra

What anatomic feature divides the upper and lower anal canal?

Pectinate line

What muscle holds the rectum in a 90° flexure?

Puborectalis muscle

Describe the arterial supply, venous drainage, and innervation of internal hemorrhoids:

Vasculature = superior rectal artery/vein (drains to portal circulation); visceral innervation → not painful

Describe the arterial supply, venous drainage, and innervation of external hemorrhoids:

Vasculature = inferior rectal artery/vein (drains to systemic circulation via IVC); somatic innervation → painful

What type of muscle is found in the internal anal sphincter?

Smooth muscle (under involuntary control via autonomic innervation)

What type of muscle is found in the external anal sphincter?

Striated muscle (under voluntary control via the pudendal nerve)

What are the boundaries of Hesselbach triangle?

Inferior epigastric artery, inguinal ligament, lateral border of rectus abdominus muscle

Name the types of hernia:

Peritoneum protrudes through Hesselbach triangle, medial to the inferior epigastric artery

Direct hernia

Retroperitoneal structures to enter the thorax because of defective development of pleuroperitonial membrane

Diaphragmatic hernia

Peritoneum protrudes through both the internal (deep) and external (superficial) inguinal rings

Indirect hernia

Stomach herniates upward through the esophageal hiatus of the diaphragm

Hiatal hernia

Occurs in infants as a result of failure of processus vaginalis to close

Indirect hernia

Protrudes below the inguinal ligaments and lateral to the pubic tubercle; more common in females

Femoral hernia

PHYSIOLOGY

Saliva

Which three glands produce saliva?

1. Parotid

2. Submandibular

3. Sublingual

Name three important functions of saliva:

1. Protection of dental health by buffering oral bacterial acids

2. Digestion (starches by a-amylase); triglycerides (TGs) by lingual lipase

3. Lubrication of food with mucins

What determines the relative composition of salivary contents?

Flow rate

How is the regulation of saliva production unique?

It is stimulated by both parasympathetic and sympathetic activity.

GI Hormones and Secretions

Name the source of the following GI secretory products:

Intrinsic factor (IF)

Parietal cells (stomach)

Pepsinogen

Chief cells (stomach)

Histamine

Mast cells (stomach)

Gastric acid (H+)

Parietal cells (stomach)

Gastrin

Antral G cells and duodenum

Bicarbonate

Surface mucosal cells (of stomach and duodenum)

Secretin

S cells (duodenum)

Somatostatin

D cells (duodenum)

Cholecystokinin (CCK)

I cells (duodenum) and jejunum

Gastric inhibitory peptide (GIP)

Duodenum and jejunum

For each of the following substances, state the factors that regulate its secretion:

Gastric acid (H+)

↑ By histamine, acetylcholine (ACh), gastrin; ↓ by prostaglandin, somatostatin, GIP

Pepsinogen

↑ By vagal stimulation (ACh) and low pH

Gastrin

↑ By small peptides and amino acids (AAs) (Phe and Trp = most potent), gastric distention, and vagus (via gastrin-releasing peptide[GRP]); ↓ by pH 3.0 and secretin

Bicarbonate in pancreatic secretions

↑ By secretin (potentiated by CCK and vagal input)

Secretin

Acid (H+ and fatty acids [FAs]) in the duodenum

Somatostatin

↑ By acid; ↓ by vagus

CCK

↑ By FAs, AAs, and small peptides

GIP

↑ By FAs, AAs, and oral glucose

List the most important functions of the following GI secretions:

IF

Binds vitamin B_12 for uptake in terminal ileum

Gastric acid (H+)

Converts pepsinogen to pepsin and sterilizes chyme. Note: inadequate acid production →↑ risk of Salmonella infections

Pepsinogen

Digests protein

Gastrin

↑ Secretion of IF, HCl, and pepsinogen; stimulates gastric motility and growth of gastric mucosa

Bicarbonate

Neutralizes acid → prevents autodigestion

Secretin

↑ Pancreatic HCO_3– secretion; ↓ gastric acid secretion

Somatostatin

↓ H+ and pepsinogen secretion, ↓ pancreatic and SI secretions, ↓ gallbladder contraction, ↓ release of both insulin and glucagon

CCK

↑ Gallbladder contraction, ↑ pancreatic enzyme secretion, ↓ gastric emptying

GIP

↑ Insulin (especially in response to oral glucose); ↓ H+ secretion

Which enzyme in the parietal cell catalyzes the production of H and HCO_3- from CO_2 and H_2O?

Carbonic anhydrase

How is H+ secreted into the lumen of the stomach?

H+/K+ ATPase pumps H out of cells and Cl- diffuses concurrently to maintain electrical neutrality forming HCl.

Which chemical potentiates the actions of ACh and gastrin in stimulating secretion?

Histamine. (This is why H receptor blockers are so effective in treating ulcers.)

Which prototypical drug blocks the effects of histamine at the level of the parietal cell?

Cimetidine (an H receptor blocker)

Why does not atropine block vagally mediated gastrin secretion?

Vagal stimulation of acid production is independent of ACh. (It is mediated by GRP.)

Which GI hormone is released by the small intestine in response to fats, proteins, and carbohydrates?

GIP

GI Motility

What are the two main divisions of the enteric nervous system?

1. Extrinsic (parasympathetic and sympathetic nervous systems)

2. Intrinsic (enteric nervous systems)

Parasympathetic innervation of the GI tract occurs via which nerves and has what general effect?

Vagus and pelvic → usually stimulatory

Sympathetic innervation of the GI tract occurs via which nerves and has what general effect?

Fibers originate in spinal cord and synapse in the celiac and superior mesenteric ganglia → usually inhibitory.

What term is used to describe the vasovagal reflex that accomodates for food entering the stomach?

Receptive relaxation

What reflex mediates colonic motility in response to food in the stomach?

Gastrocolic reflex

What are the two components of the gastrocolic reflex?

1. Fast: mediated by the autonomic nervous system

2. Slow: mediated by CCK and gastrin

What two centers of the brain are integral to vomiting?

1. Chemoreceptor trigger zone (floor of the fourth ventricle)

2. The vomiting center of the medulla

What pacemaker cells in the GI tract regulate the basal rate of gut contraction?

Interstitial cells of Cajal (ICC)

What are the frequencies of ICC’s pacemaker activities?

Stomach—3/min, duodenum—12/min, ileum—10/min, colon—3/min

Miscellaneous GI Physiology

What part of the pancreas is responsible for synthesizing and releasing zymogens?

Secretory acinar cells

Which two chemicals stimulate the release of zymogens?

1. ACh

2. CCK

Which hormone acts on the pancreatic ductal cells to increase mucus and HCO_3- secretion?

Secretin

Name the pancreatic enzymes responsible for the following actions:

Starch digestion

α-Amylase (secreted in active form)

Protein digestion

Proteases (eg, trypsin, chymotrypsin, elastase, carboxypeptidases—secreted as proenzymes)

Fat digestion

Lipase, phospholipase A, colipase

Which enzyme catalyzes the conversion of trypsinogen into trypsin?

Enterokinase (a brush-border enzyme)

Why is the conversion of trypsin an important part of protein digestion?

Trypsin converts proenzymes to their active forms (including trypsinogen to form a positive-feedback loop)

What is the rate-limiting step in carbohydrate digestion?

Production of monosaccharides by oligosaccharide hydrolases (at brush border)

What are the five major components of bile?

1. Water (97%)

2. Bile salts

3. Phospholipids

4. Cholesterol

5. Bilirubin (BR)

What property of bile salts allows them to solubilize lipids into micelles for absorption?

They are amphipathic (contain both hydrophilic and hydrophobic regions).

Where is bile produced and stored?

It is produced continuously by hepatocytes and stored in gallbladder.

What is the role of intestinal bacteria in the synthesis of bile acids?

They convert primary (1°) bile acids to secondary (2°) bile acids.

Which membrane protein is essential for bile acids recirculation?

Na+ -bile cotransporter in terminal ileum

Why does ileal resection result in steatorrhea?

Lack of bile acid recirculation → depletion of the bile acid pool → impaired fat absorption

What types of carbohydrates can be absorbed?

Monosaccharides only (eg, glucose, galactose, fructose)

By what mechanism are carbohydrates absorbed?

Glucose/galactose: Na+ -dependent cotransport; fructose: facilitated diffusion

How are fats absorbed?

Lipase breaks triglycerides into glycerol and FAs. Short- and medium-chain FAs undergo passive diffusion; long-chain FAs form micelles with bile salts for passive diffusion.

What metabolites of protein can be absorbed by the GI tract and what type of transport molecules are involved in their absorption?

AAs, dipeptides, and tripeptides; Na+-dependent cotransporters

PATHOLOGY

Nonneoplastic Disorders of the Upper GI Tract

Name the nonneoplastic disorder of the upper GI tract with the following pathologic and clinical features:

Common vesicular circumoral lesion with eosinophilic intranuclear inclusions

Herpes labialis (usually herpes simplex virus [HSV]-1)

Connective tissue disorder characterized by xerostomia, keratoconjunctivitis sicca, and autoantibodies to SS-A (Ro) and SS-B (La)

Sjögren syndrome

Esophageal dysmotility caused by inability of the lower esophageal sphincter to relax (due to loss of ganglion cells in the myenteric plexus)

Achalasia

Type of hiatal hernia in which the stomach and the cardioesophageal junction slide in and out of the thorax

Sliding (axial) hernia

Pharyngeal outpouching involving >1 layer of the esophageal wall; results in food accumulation and chronic halitosis

Zenker (pharyngoesophageal) diverticulum

Retching-induced laceration of gastroesophageal (GE) junction resulting in hematemesis and mediastinitis; ↑ incidence in alcoholics

Mallory-Weiss tear

Complete rupture of the esophagus (all layers), often due to severe retching

Boerhaave syndrome

May result from Chagas disease causing the loss of myenteric plexus in the esophagus

2° achalasia

Hyperplasia of gastric surface mucosal cells

Ménétrier disease

Postvagotomy, unimpeded passage of hypertonic food to SI → distention and diarrhea

Dumping syndrome

Neoplastic Disorders of the Upper GI Tract

Name the neoplastic disorder of the upper GI tract described by each of the following statements:

Most common salivary gland tumor; contains a mix of epithelial and mesenchymal elements

Pleomorphic adenoma (mixed tumor)

Irregular white mucosal patches in the mouth of an AIDS patient as a result of Epstein-Barr virus (EBV)

Oral hairy leukoplakia

Accounts for 95% of oral cancers

Squamous cell carcinoma

Benign salivary tumor containing cystic spaces lined by double-layered eosinophilic epithelium (oncocytes) embedded in dense lymphoid tissue

Warthin tumor (papillary cystadenoma lymphomatosum)

Most common esophageal carcinoma; usually in proximal two-thirds; associated with alcohol and tobacco use

Squamous cell carcinoma

Intestinal metaplasia of squamous epithelium in distal esophagus in response to prolonged injury (often due to GERD)

Barrett esophagus

Mucin-producing glandular tumor of the distal one-third of the esophagus

Adenocarcinoma

Infiltrating carcinoma, causing extensive thickening of stomach wall; “leather-bottle stomach”

Linitis plastica (signet ring carcinoma)

Gastric carcinoma that has metastasized to the ovary

Krukenberg tumor

Name six important risk factors for gastric carcinoma:

These ↑ your “CHANSE” for gastric cancer:

1. C hronic gastritis

2. H elicobacter pylori infection

3. A blood type

4. N itrosamines

5. S ex (men > 50 years old)

6. E ating habits (low-fiber diet)

Name six important risk factors for esophageal carcinoma:

“ABCDEF”

1. A chalasia

2. B arrett esophagus

3. C orrosive esophagitis

4. D iverticuli

5. E sophageal webs

6. F amilial

What is the name for metastatic spread of gastric cancer to the supraclavicular node?

Virchow node

Pediatric GI Disorders

Name the GI disorder commonly diagnosed in the pediatric population with the following findings:

Difficulty with feeding starting from birth, excessive oral secretions, inability to pass NG tube, no gas in abdomen, early pneumonia

Tracheoesophageal fistula

Nonbilious projectile vomiting, abdominal “olive” in epigastric region

Pyloric stenosis

Bilious vomiting, “double bubble,” associated with Trisomy 21

Duodenal atresia

Commonly occurs at ileocecal junction, most common cause of small bowel obstruction in toddlers

Intussuseption

Failure to pass meconium in the first 48 hours of birth, abdominal distention, associated with CF

Meconium ileus

Gastritis

Name the type of gastritis associated with the following findings:

Autoimmune disorder with autoantibodies to parietal cells and IF, achlorhydria, pernicious anemia, and aging

Type A (fundal) chronic gastritis (Remember: the 5 A’s for type A)

“Coffee-ground emesis” from mucosal inflammation

Acute (erosive) gastritis

Helicobacter pylori infection

Type B (antral) chronic gastritis (B = bug)

Left shoulder pain

Perforation of ulcer → irritation of left diaphragm

Peptic Ulcer Disease

Name the type of peptic ulcer (gastric or duodenal) disease associated with each of the following findings:

Pain is greater with meals

Gastric ulcer (pain is G reater with meals) → weight loss

Pain decreases with meals

Duodenal ulcer (pain Decreases with meals) → weight gain

Almost 100% associated with H. pylori infection

Duodenal ulcer

Due to ↓ mucosal protection against gastric acid

Gastric ulcer

Associated with nonsteroidal anti-inflammatory drug (NSAID) use

Gastric ulcer

Hypertrophy of Brunner glands

Duodenal ulcer

Blood type O

Duodenal ulcer

Elevated gastrin levels

Duodenal ulcer

Due to ↑ gastric acid secretion and/or ↓ mucosal protection

Duodenal ulcer

Name four common complications of peptic ulcer disease:

1. Bleed i ng

2. Penetration

3. Perforation

4. Obstruction

Name a classic complication of posterior duodenal ulcers:

Massive hemorrhage from erosion of the gastroduodenal artery

Malabsorption

Name the malabsorption syndrome associated with each of the following pathologic and clinical findings:

Gluten sensitivity

Celiac disease (nontropical sprue)

Brush-border enzyme deficiency resulting in bacterial digestion of unabsorbed disaccharide, causing osmotic diarrhea

Disaccharidase deficiency (#1 = lactase deficiency)

Steatorrhea, weight loss, hyperpigmentation, polyarthritis, fever, and lymphadenopathy in an older, white male; infectious etiology

Whipple disease (caused by Tropheryma whippelii)

Increased risk of T-cell lymphoma, GI, and breast malignancy

Celiac disease

Autosomal recessive (AR) defect in chylomicron assembly resulting in an absence of chylomicrons, very low-density lipoproteins (VLDLs), or low-density lipoprotein (LDL) in blood

Abetalipoproteinemia

Flat, proximal intestinal mucosa with marked villous atrophy; lymphocytes and plasma cells in lamina propria

Celiac disease

Distinctive periodic acid-Schiff (PAS)-positive macrophages in intestinal mucosa

Whipple disease

Associated with HLA-DQ2 and HLA-DQ8

Celiac disease

Gram-positive actinomycetes

Whipple disease

Acanthocytes (burr cells) in blood

Abetalipoproteinemia

Diverticular Disease

What is the most common cause of painless bleeding from the lower GI tract?

Diverticulosis

What is the prevalence of diverticulosis in the US population older than age 60?

~50%

What part of the colon is most frequently affected by diverticulosis?

Sigmoid colon

Name the disorder characterized by diverticular inflammation causing left lower quadrant (LLQ) pain, anorexia, nausea, and vomiting:

Diverticulitis

Name four complications of diverticulitis:

1. Perforation

2. Peritonitis

3. Abscess

4. Obstruction

What part of the GI tract is most commonly affected by ischemic bowel disease?

“Watershed” areas (splenic flexure, rectosigmoid junction)

Define intussusception.

Telescoping of the intestines resulting in intestinal obstruction

Define volvulus.

Complete twisting of the bowel around its mesenteric base

Where does volvulus most commonly occur?

Sigmoid colon (more common in elderly)

Name the inflammatory bowel disease which is often characterized by overgrowth of exotoxin-producing bacteria:

Pseudomembranous colitis

Which organism is responsible for pseudomembranous colitis?

Clostridium difficile

What disorder is characterized by nausea, vomiting, anorexia, leukocytosis, and pain at McBurney point?

Appendicitis

Inflammatory Bowel Disease

Ulcerative colitis or Crohn’s disease?

Pancolitis with crypt abscesses

Ulcerative colitis (UC)

Fistulas and fissures

Crohn’s disease Both

Associated with ankylosing spondylitis

Both

Associated with sclerosing cholangitis

UC

Amyloidosis

Crohn’s disease

Can lead to toxic megacolon

UC

Longitudinal ulcers

Crohn’s disease

Punched-out aphthous ulcers

Crohn’s disease

Increased risk of colorectal carcinoma

UC >>> Crohn’s disease

Skip lesions

Crohn’s disease

Can involve any portion of the GI tract (usually terminal ileum and colon)

Crohn’s disease

“String sign” on x-ray (due to bowel wall thickening)

Crohn’s disease

Associated with pyoderma gangreosum

Both

Transmural inflammation

Crohn’s disease

Noncaseating granulomas

Crohn’s disease

Cobblestone mucosa

Crohn’s disease

Neoplastic Disorders of the Lower GI Tract

What is the most common histologic type of GI lymphomas?

95% are B cell (MALT omas).

What is the most common tumor of the appendix?

Carcinoid tumor

What type of cells give rise to carcinoid tumors?

Neuroendocrine cells

What substances are secreted from carcinoid tumors?

Serotonin, histamine, and prostaglandins

Which carcinoid tumors tend to be more aggressive?

Ileal, gastric, and colonic

Metastases to which organ result in carcinoid syndrome?

Liver

Name five clinical findings of carcinoid syndrome:

1. Vasomotor dysfunction

2. GI hypermotility

3. Bronchoconstriction

4. Hepatomegaly

5. Right-sided heart valve stenosis

What laboratory test is used in the diagnosis of carcinoid syndrome?

5-Hydroxyindoleacetic acid (5-HIAA) in urine

Name the types of neoplastic polyp:

Usually benign and pedunculated; most common

Tubular adenoma (75%)

Highly malignant; sessile tumor > ↓ cm with fingerlike projections

Villous adenoma

Shares features of both other types of polyps

Tubulovillous adenoma

Name five major risk factors for colon cancer:

1. Presence of colonic villous adenomas

2. Inflammatory bowel disease

3. Low-fiber, high animal fat diet

4. Age (> 60)

5. Positive family/personal history

How does colorectal carcinoma classically present?

Left side lesions → blood in stool; right side lesions → anemia (from occult blood loss)

Where is the most common site for colorectal cancer?

Sigmoid colon

Name the autosomal dominant (AD) polyposis syndrome associated with each of the following findings:

Colonic polyps, osteomas, and soft tissue tumors; associated with abnormal dentition

Gardner syndrome

Hundreds of colonic polyps; malignant potential ~100%

Familial adenomatous polyposis (FAP)

Colonic polyps and CNS tumors; malignant potential ~100%

Turcot syndrome

Defect in DNA repair → many colonic lesions (especially proximal); malignant potential ~50%

Hereditary nonpolyposis colorectal carcinoma (HNPCC)

Benign, hamartomas of GI tract; melanotic pigmentation of hand, mouth, and genitalia; no malignant potential (but ↑ risk of other tumors)

Peutz-Jeghers syndrome

What are the three tumor syndromes in which the APC gene is mutated?

1. FAP

2. Gardner syndrome

3. Turcot syndrome

Pancreatitis and Pancreatic Cancer

Name nine causes of acute pancreatitis:

“GET SMASHeD”

1. Gallstones (major cause)

2. Ethanol (major cause)

3. Trauma

4. Steroids

5. Mumps

6. Autoimmune disorder

7. Scorpion sting

8. Hyperlipidemia

9. Drugs (especially ddI)

Other causes: ischemia, infections, pancreatic cancer, and peptic ulcer disease

Name seven possible sequelae of acute pancreatitis:

1. Progression to chronic pancreatitis

2. Abscess

3. Pseudocyst

4. Hypocalcemia

5. Focal fibrosis and diffuse fat necrosis

6. Acute respiratory distress syndrome (ARDS)

7. Disseminated intravascular coagulation (DIC)

Name four common laboratory abnormalities in acute pancreatitis:

1. ↑ Serum amylase (within 24 hours)

2. ↑ Serum lipase (72-96 hours)

3. Hypocalcemia

4. Glycosuria

Name five causes of chronic pancreatitis:

“ABCCD”

1. Alcoholism (#1 in adults)

2. Biliary tract disease

3. Cystic fibrosis (#1 in kids)

4. Ca2+ (hypercalcemia)

5. Divisum (pancreas divisum)

Most pancreatic tumors are found in what region of the pancreas?

Two-thirds of pancreatic tumors are found in the pancreatic head.

What is a common clinical presentation of a mass in the pancreatic head?

Painless jaundice causing malabsorption and Courvoisier (enlarged, palpable) gallbladder

What is Trousseau syndrome?

Migratory thrombophlebitis associated with visceral cancer, commonly pancreatic adenocarcinoma

What are the two most commonly mutated genes causing pancreatic adenocarcinoma?

1. K-ras (> 90% mutated)

2. p53 (60%-80% mutated)

What is the prognosis for pancreatic adenocarcinoma?

Averages 6 months or less (very aggressive)

Disorders of Bilirubin Metabolism

What type of hyperbilirubinemia results from cholestasis?

Conjugated

Name the hereditary hyperbilirubinemia described in each of the following statements:

Mildly ↓ UDP-glucuronyl transferase; asymptomatic; associated with stress in 6% of people

Gilbert syndrome

AR defect causing ↓ canalicular excretion of BR conjugates → grossly black liver; asymptomatic

Dubin-Johnson syndrome

AR absence UDP-glucuronyl transferase → ↑ unconjugated BR → jaundice, kernicterus, early death

Crigler-Najjar syndrome, type I

AR defect causing asymptomatic, conjugated bilirubinemia

Rotor syndrome

Liver Disorders

What three pathologic characteristics define cirrhosis?

1. Fibrosis

2. Nodular regeneration of hepatocytes

3. Disruption of parenchymal architecture

Name four common causes of micronodular cirrhosis:

1. Chronic alcoholism (think of a micro brewery)

2. Hereditary hemochromatosis

3. 1° biliary cirrhosis

4. Wilson disease (hepatolenticular degeneration

Name four common causes of macronodular cirrhosis:

1. Hepatitis B virus (HBV)

2. Hepatitis C virus (HCV)

3. α_1-Antitrypsin deficiency

4. Wilson disease

List the effects of hepatic failure on the following body systems:

Eye

Scleral icterus

Neurologic

Coma, hepatic encephalopathy (asterixis, hyperreflexia, behavioral changes)

Systemic

Peripheral edema, malnutrition

Skin

Jaundice, palmar erythema, spider angiomata, caput medusae

Reproductive

Testicular atrophy, gynecomastia, loss of pubic hair

Hematopoietic

Anemia, bleeding tendency (↓ coagulation factors), splenomegaly

Renal

Hepatorenal syndrome (ARF 2° to hypoperfusion)

GI

Fetor hepaticus, ascites, esophageal varices, hemorrhoids

Name the liver disorder associated with each of the following findings:

Mallory bodies

Alcoholic hepatitis

Occlusion of IVC or hepatic veins with centrilobular congestion → congestive liver disease; associated with polycythemia, pregnancy, and hepatocellular carcinoma

Budd-Chiari syndrome

Obliteration of hepatic vein radicals following bone marrow transplant

Veno-occlusive disease

Copper deposition in liver, kidneys, brain, and cornea → asterixis, basal ganglia degeneration, dementia

Wilson disease (hepatolenticular degeneration)

AST:ALT ratio > 1.5

Alcoholic hepatitis

Lymphoid aggregates and interface hepatitis

Chronic hepatitis

May be incidental finding in young woman taking oral contraceptives

Hepatic adenoma

Sinusoidal hepatic dilations from use of anabolic steroids

Peliosis hepatis

Hemolysis, elevated LFTs, and low platelets in a pregnant woman

HELLP syndrome (hepatic disease of pregnancy)

Elevated α-fetoprotein (AFP)

Hepatocellular carcinoma

Name the etiology of cirrhosis associated with each of the following findings:

Panacinar emphysema

α_1-Antitrypsin deficiency

Decreased ceruloplasmin

Wilson disease (hepatolenticular degeneration)

Triad of bronze diabetes, skin pigmentation, and micronodular pigment cirrhosis

Hemochromatosis

Antimitochondrial antibodies

Primary biliary cirrhosis

Nutmeg liver

Congestive heart failure

Kayser-Fleischer rings

Wilson disease (hepatolenticular degeneration)

Micronodular fatty liver; portal hypertension, asterixis, jaundice, and gynecomastia

Chronic alcohol abuse

↑ Ferritin, transferrin, and total iron; ↓ total iron-binding capacity (TIBC)

Hereditary hemochromatosis. Note: total body iron is sometimes high enough to trigger metal detectors.

Name the major risk factors for hepatocellular carcinoma:

“WATCH for ABC”

Wilson disease

α_1-AntiTrypsin

Carcinogens (eg, aflatoxin B_1, polyvinyl chloride)

Hemochromatosis

Alcoholic cirrhosis

Hepatitis B

Hepatitis C

Hepatocellular carcinoma tends to spread through which route?

Hematogenous

What is the most common type of malignancy in the liver?

Metastasis

Which primary tumors tend to metastasize to the liver?

Colon > Stomach > Pancreas > Breast > Lung (Remember: “Cancer Sometimes Penetrates Benign Liver!”)

Name the hepatobiliary disorder associated with the following:

Strawberry gallbladder

Cholesterolosis

Associated with Opisthorchis sinenis (liver fluke) infection in Asia

Cholangiocarcinoma

Tumor arising at the junction of the left and right hepatic ducts

Klatskin tumor

Inflammation of the bile duct; commonly due to Escherichia coli infection

Ascending cholangitis

Disorders of the Gallbladder

What is Courvoisier law?

An enlarged, palpable gallbladder with jaundice is likely the result of an underlying malignancy (often in head of the pancreas) and not from a stone in the common duct (because gallbladder is typically too scarred from infection).

What is Charcot triad?

Spiking fevers with chills, jaundice, and right upper quadrant (RUQ) pain (biliary colic); strongly suggests cholangitis

What are the risk factors for cholelithiasis?

4 F’s: Fertile, Fat, Forty-year-old Female

What is the most common type of gallstone?

Mixed stone (components of pigment and cholesterol stones)

Name six complications of cholelithiasis:

1. Biliary colic and common bile duct obstruction

2. Cholecystitis (acute or chronic)

3. Ascending cholangitis

4. Acute pancreatitis

5. Gallstone ileus

6. Malignancy (adenocarcinoma)

Viral Hepatitis

Name the hepatitis virus (viruses) associated with the following features:

Fecal-oral transmission

Hepatitis A virus (HAV)

Water-borne transmission

Hepatitis E virus (HEV)

Infection may lead to a carrier state

HBV, HCV, and hepatitis D virus (HDV, delta agent)

Defective virus requiring HBsAg as its envelope

HDV (delta agent)

Sexual, parenteral, and transplacental transmission

HBV, HCV, HDV

DNA hepadnavirus

HBV

High mortality rate in pregnant women

HEV

Associated with IV drug use

HCV

Long incubation (~3 months)

HBV

Increased risk of hepatocellular carcinoma

HBV, HCV

Immune globulin vaccine available

HAV, HBV (and HDV)

Short incubation (~2 weeks)

HAV

Name the hepatitis serologic marker described below:

Antigen found on surface of HBV; continued presence suggests carrier state

HBsAg

Antigen associated with core of HBV

HBcAg

Antigen in the HBV core that indicates transmissibility

HBeAg

Antibody suggesting low HBV transmissibility

HBeAb

Acts as a marker for HBV infection during the “window” period (acute phase)

IgM-HBcAb

Provides immunity to HBV

HBsAb

What is the “window” period of a hepatitis infection?

Period during acute infection when HBsAg has become undetectable, but HBsAb has not yet appeared

Infectious Diarrhea

Name six infectious causes of bloody diarrhea:

1. Salmonella

2. Shigella

3. Campylobacter jejuni

4. Enteroinvasive and enterohemorrhagic E. coli

5. Yersinia enterocolitica

6. Entamoeba histolytica

Name the diarrhea-causing organism associated with the following statements:

Most common cause of diarrhea in infants

Rotavirus

Ten to twelve loose, bloody, and mucous diarrhea stools per day due to ingestion of cysts

Entamoeba histolytica

Comma-shaped organisms causing rice-water stools

Vibrio cholera

Second to rotavirus as a cause of gastroenteritis in kids

Caliciviruses (Norwalk-like and Sapporo-like)

Bloody diarrhea; very low ID_50 (small numbers of organisms can cause disease); nonmotile

Shigella

Usually transmitted from pet feces

Yersinia enterocolitica

Motile; lactose nonfermenter; causes bloody diarrhea

Salmonella

Comma- or s-shaped organisms causing bloody diarrhea; grows at 42°C

Campylobacter jejuni

Watery diarrhea with extensive fluid loss in AIDS patient

Cryptosporidium

Foul-smelling diarrhea after returning from a camping trip

Giardia lamblia

Watery diarrhea caused by antibiotic-induced suppression of colonic flora

Clostridium difficile

Name the organism responsible for food poisoning from the following items:

Reheated rice

Bacillus cereus

Reheated meat dishes

Clostridium perfringens

Improperly canned food

Clostridium botulinum

Contaminated seafood or raw oysters

Vibrio parahaemolyticus and Vibrio vulnificus

Meats, mayonnaise, custards

Staphylococcus aureus. Note: starts and ends quickly

Undercooked beef products

Escherichia coli O157:H7

Raw poultry, milk, eggs, and meat

Salmonella

PHARMACOLOGY

For each of the following drugs, provide:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects and unique toxicity (TOX) (if any)

Omeprazole, pantoprazole, lansoprazole

MOA: Irreversibly inhibits H+/K+-ATPase in parietal cells (proton pump inhibitor)

IND: Peptic ulcer disease, Zollinger-Ellison syndrome, erosive esophagitis

TOX: Liver toxicity, pancreatitis, agranulocytosis (rare)

Cimetidine, ranitidine, famotidine, nizatidine

MOA: H_2 receptor antagonist in parietal cell

IND: GE reflux disease

TOX: Endocrine effects (gynecomastia—primarily caused by cimetidine, galactorrhea, ↓ sperm count), potent inhibitor of P-450, ↓ renal creatinine clearance

Misoprostol

MOA: PGE_1 analog →↑ secretion of gastric mucus and bicarbonate

IND: Prophylaxis for NSAID-induced peptic ulcer disease (PUD); maintenance of a patent ductus arteriosus (PDA)

TOX: Abortifacient

Aluminum sucrose sulfate (sucralfate)

MOA: Polymerizes in stomach → binds to injured tissue, forming a protective coating over ulcers (Note: requires an acidic environment)

IND: Peptic ulcer disease

TOX: Osteodystrophy, osteomalacia (mainly in pts with renal failure)

Ondansetron, granisetron

MOA: 5-HT_3 receptor antagonist

IND: Postoperative nausea/vomiting, chemotherapy-induced emesis

TOX: Headache, diarrhea

Meclizine

MOA: H_1 receptor antagonist

IND: Motion sickness

TOX: Teratogenic

Loperamide, diphenoxylate

MOA: Antimotility agents (meperidine analogs)

IND: Diarrhea

TOX: Toxic megacolon in kids (loperamide)

Metoclopramide

MOA: Stimulates ACh release →↑ upper GI motility

IND: Nausea, ileus

TOX: Sedation, diarrhea, and extrapyramidal symptoms (EPS) (especially in kids)

Lactulose

MOA: Osmotic laxative

IND: Hyperammonemia, colonic lavage precolonoscopy

TOX: Dehydration with overuse

What is “triple therapy” for peptic ulcer disease?

Proton pump inhibitor (PPi), bismuth salicylate, and two of the following antibiotics: metronidazole, amoxicillin, clarithromycin, or tetracycline

What is the most important approach to healing peptic ulcers?

Eradicating H. pylori

How long does proton pump inhibition last?

48 hours

Name two uses for bismuth subsalicylate:

1. Helicobacter pylori infection

2. Traveler diarrhea

What two weak bases that are used as antacids have minimal systemic absorption?

1. MgOH_2

2. AlOH_3 (combined to make milk of magnesia)

For each of the following antacids list the toxicity/toxicities:

Antacids

Hypokalemia, alter absorption of other drugs

Sodium bicarbonate

Systemic alkalinization

Aluminum hydroxide

Constipation

Magnesium hydroxide

Diarrhea

Name the therapy of choice for each of the following disorders:

Hereditary hemochromatosis

Repeated phlebotomy and deferoxamine

Wilson disease

Chelation therapy (with penicillamine)

Acute cholecystitis from gallstones

Cholecystectomy

CHAPTER 8

Reproduction and Endocrinology

EMBRYOLOGY

During embryogenesis, when is male/female phenotypic differentiation complete?

By week 20

Which gene determines phenotypic differentiation?

Sry gene (encodes for a protein called testis-determining factor [TDF])

Which cells secrete Mullerian-inhibiting factor (MIF) during fetal development?

Sertoli cells

What factors are required to direct the indifferent embryo into a male phenotype?

TDF, MIF, testosterone, and dihydrotestosterone (DHT)

In what structure, within the testes, does spermatogenesis occur?

Seminiferous tubules

What molecule is the primary (1°) source of energy for sperm?

Fructose

Give the number of chromosomes and amount of DNA found in each of the following cell types:

Spermatogonia

46,2N

1° spermatocyte/oocyte

46,4N

Secondary (2°) spermatocyte/oocyte

23,2N

Spermatid/ovum

23,1N

What stage is each cell type halted in and when is the stage finally completed?

1° oocyte

Prophase I, just prior to ovulation

2° oocyte

Metaphase II, at fertilization

Name the structure of the mature sperm associated with each of the following statements:

Derived from the Golgi apparatus

Acrosomal cap

Contains mitochondria

Middle piece (neck)

Derived from one of the centrioles

Flagellum (tail)

Name the congenital disorder that results from each of the following aberrations:

Complete lack of fusion of paramesonephric ducts

Double uterus with double vagina

Partial fusion of the paramesonephric ducts

Bicornate uterus

Testes fail to descend into the scrotum

Cryptorchidism (bilateral → sterility)

Patency of processus vaginalis

If small → hydrocele; if large → congenital inguinal hernia

Failure of urethral folds to close

Hypospadias (penile urethra opens on inferior/ventral side)

Faulty positioning of genital tubercle

Epispadias (penile urethra opens on superior/dorsal side)

Name the embryonic structure that gives rise to each of the following tissues:

Thyroid gland

Thyroid diverticulum

Thymus, inferior parathyroids

Third branchial pouch

Superior parathyroids and the parafollicular “C” cells

Fourth branchial pouch (fourth is superior to third)

Chromaffin cells of adrenal medulla

Neural crest cells

Adrenal cortex

Mesoderm

What is the most common site for ectopic thyroid tissue and why?

The tongue; during development, the thyroid migrates caudally from the level of the developing tongue.

Which syndrome is caused by a failure of the development of the third and fourth pharyngeal pouches?

DiGeorge syndrome

Describe the clinical features of DiGeorge syndrome:

“CATCH 22”

Cardiac abnormalities (eg, tetralogy of Fallot, interrupted aortic arch)

Abnormal facies

Thymic aplasia/hypoplasia and T-cell deficiency

Cleft palate

Hypocalcemia → tetany Chromosome 22q11

ANATOMY

Name the five types of endocrine cells found in the pars distalis of the anterior pituitary:

1. Somatotrophs (~50%)

2. Mammotrophs

3. Thyrotrophs

4. Corticotrophs

5. Gonadotrophs

Where is antidiuretic hormone (ADH) primarily produced?

Supraoptic nucleus of hypothalamus

Where is oxytocin primarily produced?

Paraventricular nucleus of hypothalamus

What part of the pituitary stores and releases ADH and oxytocin?

Neurohypophysis (posterior pituitary)

Where is the hypophyseal portal system located?

Adenohypophysis (in the pars tuberalis)

What is the 1° arterial supply to the gonads?

Testicular/ovarian arteries (directly from abdominal aorta branches)

What is the 1° venous drainage of the gonads?

Left testicular/ovarian vein → left renal vein; right testicular/ovarian vein → inferior vena cava (IVC)

Which lymph nodes filter lymph from the gonads?

Deep lumbar/para-aortic nodes

Which lymph nodes filter lymph from the scrotum?

Superficial inguinal nodes

What are the two pathways for venous drainage from the prostate gland?

1. Prostatic venous plexus → internal iliac veins → IVC

2. Prostatic venous plexus → vertebral venous plexus → cranial dural sinuses

Describe the type of innervation for each phase of the male sexual response cycle:

Erection

Parasympathetic nerves (Point)

Emission

Sympathetic nerves (Shoot)

Ejaculation

Visceral autonomic and somatic nerves

Name the structure(s) contained in the following uterine ligaments:

Transverse cervical (cardinal) ligament

Uterine vessels

Suspensory ligament of ovaries

Ovarian vessels, lymphatics, autonomic nerves

Broad ligament

Round ligaments of the uterus, ovarian ligament, ureters, uterine tubes, and uterine vessels

What is the anatomic relationship of the ureter and the uterine artery?

Ureter lies posterior and inferior to uterine artery. “Water (ureter) under the bridge (uterine artery)”

What is the normal position of the uterus?

Anteverted (uterus to cervix) and anteflexed (cervix to vagina)

What is the landmark for a pudendal nerve block?

Ischial spine

Name the part of the fallopian tube described below:

Opens into the peritoneal cavity

Infundibulum

Site of fertilization

Ampulla

Opens into the uterine cavity

Intramural

Majority of the length of the tube

Isthmus

Describe the venous drainage of the adrenal glands.

Right adrenal vein → IVC; left adrenal vein → left renal vein

What type of nerves synapse in the adrenal medulla?

Preganglionic sympathetic (through splanchnic nerves)

In the adrenal medulla, onto what cells do the preganglionic sympathetic nerves synapse?

Chromaffin cells → secrete catecholamines

PHYSIOLOGY

Second Messengers

Name the second messenger mechanism used by each of the f ollowing hormones:

Hypothalamic hormones— gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), growth hormone-releasing hormone (GHRH), oxytocin, ADH (Vj receptor)

Inositol triphosphate (IP_3)

Hypothalamic hormones— corticotropin-releasing hormone and ADH (V_2receptor)

cAMP

Anterior pituitary hormones— luteinizing hormone (LH), follicle-stimulating hormone (FSH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH)

Cyclic adenosine monophosphate (cAMP)

Growth hormone (GH)

Tyrosine kinase activation

Insulin

Tyrosine kinase activation

Melanocyte-stimulating hormone (MSH)

cAMP

Angiotensin II

IP_3

Calcitonin

cAMP

Glucagon

cAMP

Parathyroid hormone (PTH)

cAMP

Insulin-like growth factor (IGF)-l

Tyrosine kinase activation

Atrial natriuretic peptide (ANP)

Cyclic guanosine monophosphate (cGMP)

Nitric oxide

cGMP

Steroid Hormones

How do steroid hormones circulate in the body?

They are bound to specific globulin carrier proteins (which ↑ solubility and delivery to target organs).

How are the cellular effects of steroids mediated?

Steroids pass through the cell membrane, bind cytoplasmic receptors, and translocate to the nucleus where they influence gene expression.

Adrenal Glands

Name the three layers of the adrenal cortex and their major secretory products:

GFR (from outside to inside), ”the deeper you go, the sweeter it gets: salt, sugar, sex”

1. Zona Glomerulosa— mineralocorticoids

2. Zona Fasciculata—glucocorticoids

3. Zona Reticularis—andogrens

How does the secretion of glucocorticoids vary throughout the day?

Highest before waking and lowest at midnight

By what mechanism does ACTH increase steroid hormone synthesis?

Stimulates cholesterol desmolase

What is the effect of glucocorticoids on ACTH and cortisol secretion?

Potent glucocorticoids inhibit ACTH and cortisol secretion (a negative feedback mechanism).

What test is used to evaluate the response of the hypothalamic-pituitary axis to glucocorticoids?

Dexamethasone suppression test

Name four general actions of cortisol:

1. Stimulates gluconeogenesis (↑ protein catabolism and lipolysis)

2. Anti-inflammatory effects (block arachidonic acid pathway)

3. Acute exposure enhances immune response; chronic exposure suppresses immune response (inhibits interleukin [ILJ-2 production)

4. Maintains vascular responsiveness to catecholamines

Name three specific actions of aldosterone:

1. ↑ Renal Na+ reabsorption

2. ↑ Renal K+ secretion

3. ↑ Renal H+ secretion

Sex Hormones

What is the function of LH in male reproduction?

LH acts on Leydig cells → stimulates cholesterol desmolase → testosterone

What is the function of FSH in male reproduction?

FSH acts on Sertoli cells → spermatogenesis and secretion of inhibin (inhibits FSH)

How does testosterone regulate LH secretion?

Acts to ↓ release of GnRH from hypothalamus and to ↓ release of LH from adenohypophysis

Which enzyme is required to convert testosterone to its active form, DHT?

5-α-Reductase

Which enzyme catalyzes conversion of testosterone to estrogen?

Aromatase

Name three androgens (in order of decreasing potency) and where they are produced:

1. DHT (prostate, peripheral tissues)

2. Testosterone (testes, adrenals)

3. Androstenedione (adrenals)

Name five important functions of testosterone:

1. Sexual differentiation during development

2. 2° Sexual development, growth spurt, and fusion of epiphyseal plates

3. ↑ Libido

4. Anabolic effects

5. Spermatogenesis maintenance

What is the average age of menarche?

Between 11 and 14 years (in the United States)

How does GnRH release change during puberty?

Pulsatile release of GnRH begins and it upregulates its own receptors in the adenohypophysis.

What is the function of LH in female reproduction?

LH acts on theca cells → stimulates cholesterol desmolase → testosterone

What is the function of FSH in female reproduction?

FSH acts on granulosa cells → stimulates aromatase → estrogen

What happens to LH:FSH ratio during puberty?

LH >> FSH

Where is estrogen made?

Blood (via aromatase), ovaries (estradiol), placenta (estriol), and testes

What is the relative potency of the major estrogens?

Estradiol > estrone > estriol

Which estrogen is an indicator of fetal well-being?

Estriol (↑ 1000 × in pregnancy)

Where is progesterone produced?

Corpus luteum, adrenal cortex, placenta, and testes

Decide whether each of the following are characteristics of estrogen, progesterone, or both:

Development of genitalia

Estrogen

Growth of follicle

Estrogen

Proliferation of endometrium

Estrogen

Maintains endometrium

Progesterone

Maintains pregnancy

Both

Produces thick cervical mucus

Progesterone

Hepatic synthesis of transport proteins

Estrogen

↓ Myometrial excitability

Progesterone

Development of breasts

Both

↑ Body temperature

Progesterone

Spiral artery development

Progesterone

LH surge

Estrogen

Typical female fat distribution

Estrogen

Uterine smooth muscle relaxation (prevents contractions)

Progesterone

Decrease → endometrial sloughing

Progesterone

Pubertal development

Estrogen

What are the two main phases of the menstrual cycle and when do they occur?

1. Follicular phase (days 1-14)

2. Luteal phase (days 14-28)

Classify the following as characteristics of the f ollicular or luteal phase:

Graafian follicle matures

Follicular phase

Corpus luteum develops causing the release of estrogen and progesterone

Luteal phase (early)

Basal body temperature increases

Luteal phase

Oocyte progresses from meiosis I to meiosis II

Follicular phase

Endometrial glands grow → spiral arteries

Luteal phase

FSH and LH levels suppressed

Follicular phase

Endometrial proliferation

Follicular phase

Progesterone peaks

Luteal phase

Menses

Follicular phase(early)

When does ovulation occur?

14 days before menses (regardless of cycle length)

What changes in cervical mucus occur during ovulation?

Cervical mucus is thinnest and most penetrable during ovulation.

What endocrine change induces ovulation?

Estradiol burst at end of follicular phase causes a positive feedback effect, resulting in a surge of LH.

Which hormone prevents lactation during pregnancy?

High estrogen and progesterone block the effects of prolactin on the breast.

Where is hCG made and what is its function?

Syncytiotrophoblast of placenta produces hCG to maintain corpus luteum so it can produce progesterone during the first trimester until placenta can produce progesterone during the second and third trimester.

Name three scenarios in which hCG is elevated:

1. Pregnancy (in urine 10 days after fertilization)

2. Hydatidiform moles

3. Choriocarcinoma

hCG peaks at what gestational age?

Gestational week 9

What happens to estrogen and progesterone just prior to delivery?

Both increase throughout; near term estrogen:progesterone ratio increases.

What is the average age of menopause?

51 (tends to occur earlier in smokers)

Name four hormonal changes characteristic of menopause:

1. ↓ Estrogen

2. ↑↑ FSH

3. ↑ LH

4. ↑ GnRH

Name four clinical findings characteristic of menopause:

Menopause wreaks ”HAVOC” on your body

1. Hot flashes

2. Atrophy of Vagina

3. Osteoporosis

4. Coronary artery disease risk increases

Anterior Pituitary

Name the hormones produced by the anterior pituitary:

”FLAT PiG” plus melanotropin (MSH)

FSH

LH

ACTH

TSH

Prolactin

GH

Name four compounds derived from proopiomelanocortin (POMC):

1. ACTH

2. MSH

3. β-Lipotropin

4. β-Endorphin

Which hormones share a common α-subunit?

T.S.H. and TSH = The Sex

Hormones (LH, FSH, hCG) and TSH

Which glycoprotein subunit determines hormone specificity?

β-Subunit

How is GH regulated?

↑ By GHRH, sleep, stress, exercise, hypoglycemia, and puberty; ↓ by somatomedins, somatostatin, obesity, pregnancy, and hyperglycemia

Name four direct actions of GH (somatotropin):

1. ↓ Glucose uptake into cells (diabetogenic)

2. ↑ Lipolysis

3. ↑ Protein synthesis in muscle

4. ↑ Production of somatomedins (IGF)

Name three effects of IGF on growth:

1. ↑ Linear growth (pubertal growth spurt)

2. ↑ Lean body mass

3. ↑ Organ size

Which clinical syndrome results from GH hypersecretion before puberty?

Increased linear growth (gigantism)

Which clinical syndrome results from GH hypersecretion after puberty?

Acromegaly (may include glucose intolerance)

Name four functions of prolactin:

1. Stimulates milk production

2. Inhibits ovulation

3. Stimulates breast development (with estrogen)

4. Inhibits spermatogenesis

How is prolactin regulated?

↑ By estrogen (pregnancy), breastfeeding, sleep, stress, TRH, dopamine (DA) antagonists; ↓ by DA and DA agonists, somatostatin, and prolactin

What are the effects of excess prolactin?

Galactorrhea, ↓ libido, and failure to ovulate

How does prolactin inhibit ovulation?

Inhibits GnRH synthesis and release

Posterior Pituitary

Which hormones are released from the posterior pituitary and what are their function?

Oxytocin—milk ejection and uterine contraction; vasopressin (ADH)— ↑ H_2O reabsorption in kidneys

How is the release of oxytocin regulated?

↑ By suckling, dilation of the cervix, and orgasm

How is the release of ADH regulated?

↑ By high serum osmolarity, volume contraction, pain, nausea, nicotine, opiates; ↓ by low serum osmolarity, ethyl alcohol, ANP, and a-agonists

Thyroid

Which cells are responsible for thyroid hormone synthesis?

Follicular cells

Thyroid hormones are synthesized from which two molecules?

1. Iodide (I-)

2. Tyrosine

Which enzyme catalyzes the oxidation of I- to I_2?

Thyroid peroxidase

What is the relative proportion of T_4:T_3 released into the bloodstream?

T_4 = 90%, T_3 = 10%

Which thyroid hormone has the greatest biological activity?

T_3 >> T_4 (T_4 converted into T_3 by liver and kidneys)

Which protein produced by and used entirely within the thyroid is used to produce and store T_4 and T_3?

Thyroglobulin

Which carrier protein is necessary for delivery of thyroid hormone to the tissues?

Thyroxine-binding globulin (TBG)

How is thyroid hormone production regulated?

↑ By TRH and TSH; T_3 down-regulates TRH receptors in AP →↓ TSH

List four key functions of thyroid hormone:

Remember the 4 B’s of T_3

1. Brain maturation

2. Bone and cartilage growth (synergistic with GH)

3. β-Agonist effects (↑ cardiac output [CO], heart rate [HR], stroke volume [SV])

4. ↑ BMR (by ↑ Na+/K+ ATPase →↑ O_2 consumption)

Calcium Regulation

What is meant by a ”negative Ca 2+balance?”

Intestinal Ca2+ absorption is less than Ca2+ excretion.

Which is the most important hormone in the regulation of Ca2+ levels and where is it made?

PTH is synthesized and secreted by the chief cells of the parathyroid gland.

What is the major stimulus for PTH secretion?

↓ Serum Ca2+ (also mildly ↓ Mg2+

Which hormone is stimulated in response to ↑ PTH levels and ↓ serum Ca2+?

Vitamin D (1,25-(OH)2- cholecalciferol is active form.)

Which enzyme in the kidney catalyzes the activation of vitamin D?

1α-Hydroxylase

What factors increase 1α-hydroxylase activity?

↓ Serum Ca2+, ↑ PTH, ↓ serum phosphate

What clinical syndrome results from vitamin D deficiency?

Kids → rickets; adults → osteomalacia

Which hormone is released in response to ↑ serum Ca2+ and where is it made?

Calcitonin is synthesized and secreted by the parafollicular ”C” cells of the thyroid gland.

What is the effect of calcitonin on bones?

Blocks PTH-mediated resorption of bones

List the effects of PTH on each of the following organs:

Kidneys

↓ Phosphate reabsorption (by ↑ urinary cAMP), ↑ Ca2+ reabsorption in distal convoluted tubule of kidneys

Intestines

↑ Ca2+ absorption (by stimulating 1α-hydroxylase to activate vitamin D)

Bone

↑ Resorption (brings Ca2+ and phosphate into extracellular fluid [ECF])

List the effects of vitamin D on each of the f ollowing organs:

Kidneys

↑ Ca 2+ and phosphate reabsorption

Intestines

↑ Ca2+ and phosphate absorption

Bone

↑ Resorption

Pancreas

Name the three major cell types in the pancreatic islets of Langerhans, their location, and function:

1. Alpha (outer rim) → glucagons

2. Beta (central rim of islet) → insulin

3. Delta (intermixed) → somatostatin (SS) and gastrin

List three major actions of glucagon on the liver and adipose tissue:

1. ↑ Glycogenolysis and gluconeogenesis

2. ↑ Lipolysis and ketoacid production

3. ↑ Urea production

List five major functions of insulin:

1. ↓ Blood glucose

2. ↑ Fat deposition (-1lipolysis)

3. ↓ Blood amino acids

4. ↓ Blood K+

5. ↑ Protein synthesis

What is the 2° structure of insulin?

An α-chain and a (β-chain, joined by two disulfide bridges

What is C-peptide and why is it important?

A connecting peptide removed from proinsulin, packaged and secreted with insulin; serves as a useful monitor of (β-cell function and exogenous insulin administration

What are some factors that ↑ insulin secretion?

↑ Blood glucose (major), ↑ A As, ↑ FAs, GH, cortisol, glucagon, ACh

How does glucose trigger insulin release?

Binds to GLUT-2 receptor on (3-cells → closes K+ channels → cell depolarization → opens Ca2+ channels → insulin secretion

Which drugs mimic the action of glucose on (β-islet cells?

Sulfonylurea drugs

What is the effect of starvation and obesity on insulin receptor expression?

↑ In starvation; ↓ in obesity

PATHOLOGY

Male Reproductive System

Name the male genitourinary disease characterized by each of the following statements:

Intractable, painful erection; associated with venous thrombosis, trazodone, and sickle cell disease

Priapism

Inflammation of the glans associated with poor hygiene

Balanitis

Bent penis due to acquired fibrous tissue formation

Peyronie disease

Twisting of the testicular vasculature; may be spontaneous or the result of trauma

Torsion

Collection of serous fluid in the tunica vaginalis

Hydrocele

Palpable, ”bag of worms” dilation of multiple veins of the pampinif orm venous plexus of the spermatic cord

Varicocele

Acute purulent urethritis caused by gram-negative diplococci

Gonorrhea

Fever, chills, and dysuria; tender, boggy prostate; > 10 WBCs per high-power field on examination of prostatic secretions

Acute bacterial prostatitis

What are the possible sequelae of cryptorchidism?

5 to 10 × ↑ risk of germ cell tumors (GCTs), atrophy, sterility, and inguinal hernias

What is the treatment for cryptorchidism?

Orchiopexy. Note: ↓ risk of sterility, but no ↓ risk of malignancy

What are the most common etiologies of orchitis?

Mumps virus (1 week postparotiditis)

Name the most likely organism(s) responsible for epididymitis in the following groups:

Pediatric patients

Gram-negative rods

Sexually active, 35-year-old (y/o)

Neisseria gonorrhoeae, Clamydia trachomatis

Older men

Escherichia coli, Pseudomonassp.

Name the penile neoplasm associated with each of the following:

Human papillomavirus (HPV) types 6 and 11

Condyloma acuminate

Single, grayish plaque on shaft/scrotum; associated with ↑ risk of visceral malignancy

Bowen disease

Premalignant, multiple wart-like, reddish lesions with HPV type 16 viral sequence

Bowenoid papulosis

HPV types 16,18, 31, and 33

Squamous cell carcinoma of the penis

Single erythematous plaque representing carcinoma in situ of the penis, often on glans

Erythroplasia of Queyrat

What category of testicular tumors accounts for ~95% of all cases and has a peak incidence of 15- to 34-y/o?

GCTs

Name the testicular tumor associated with each of the following:

Malignant, painless enlargement of testis; most common GCT, radiosensitive

Seminoma

Malignant, chemosensitive GCT

Nonseminoma GCT

Malignant, painful GCT that has peak incidence in childhood; ↑ α-fetoprotein (AFP)

Yolk sac tumor (endodermal sinus tumor)

Malignant GCT made of 2+ embryonic layers and multiple tissue types; more common in kids

Teratoma

Malignant, aggressive GCT with > 1 neoplastic pattern

Mixed GCT

Benign, androgen-producing stromal tumor with intracytoplasmic Reinke crystals

Leydig cell tumor (interstitial)

Malignant, hemorrhagic tumor arising from trophoblastic cells; ↑ β-hCG

Choriocarcinoma

Most common testicular cancer in older men

Testicular lymphoma

Benign prostatic nodular hyperplasia or prostatic carcinoma?

Commonly affects peripheral zone

Prostatic carcinoma

Caused by age-related increase in DHT, testosterone, and estrogen

Nodular hyperplasia

Associated with bladder distention and urinary tract infections (UTIs)

Nodular hyperplasia

Enlarged, firm, nodular prostate on digital rectal examination (DRE)

Prostatic carcinoma

Commonly presents with nocturia and hesitancy

Nodular hyperplasia

Primarily affects central zone Primarily affects corpora amylacea

Nodular hyperplasia

↑ Total prostate-specific antigen (PSA), with ↓ fraction of free PSA

Prostatic carcinoma

↑ Total PSA, with proportionate ↑ in fraction of free PSA

Nodular hyperplasia

Hypermethylation of which gene is commonly associated with prostatic carcinoma?

GSTP1

What do the following findings suggest in a patient with prostatic carcinoma?

↑ Prostatic acid phosphatase

Capsule of the prostate has been penetrated.

↑ Alkaline phosphatase

Osteoblastic lesions from bony metastasis

Female Reproductive Pathology

Name the gynecologic infectious disorder characterized by each of the following features:

Clue cells in pap smear; ⊕ “whiff test”

Bacterial vaginosis (eg, Gardnerella vaginitis)

Thick, white discharge with vulvovaginal pruritis; most common form of vaginitis

Candidiasis

Fever, vomiting, diarrhea with desquamating rash; caused by exotoxins from Staphylococcus aureusassociated with tampon use

Toxic shock syndrome

Soft, painful ulcerative lesion caused by Haemophilus ducreyi

Chancroid

Firm, painless chancre caused by a spirochete Treponema pallidum

1° syphilis

Small papule/ulcer associated with lymphadenopathy and caused by C. trachomatisserotypes LI, L2, or L3

Lymphogranuloma venereum

Donovan bodies on biopsy

Granuloma inguinale

Most common STD; frequent cause of pelvic inflammatory disease (PID) (though often asymptomatic); associated with Reiter syndrome

Chlamydial cervicitis (types D-K)

Sexually transmitted infection often associated with extragenital manifestations (eg, proctitis, arthritis, and neonatal conjunctivitis)

Gonorrhea

STD resulting in benign venereal warts caused by HPV types 6 and 11

Condyloma acuminatum

Painful vesicles/ulcers; cytologic evidence of multinuclear giant cells with viral inclusions

Herpes genitalis (most often HSV type 2)

STD caused by flagellated protozoan; #2 cause of vaginitis

Trichomoniasis

Commonly caused by C. trachomatis or N. gonorrhoeae;findings may include cervical motion tenderness, salpingitis, endometritis, or tubo-ovarian abscess

PID—at ↑ risk for ectopic pregnancy and infertility

Name the female reproductive disorder associated with each of the following features:

Triad of 2° amenorrhea, obesity, and hirsutism, ↑ testosterone, ↑ LH, ↓ FSH

Polycystic ovary (Stein-Leventhal) syndrome

Menstrual disorder associated with excessive bleeding during or between menstrual periods

Dysfunctional uterine bleeding

Cyclic pain and bleeding from proliferation of ectopic endometrial tissue

Endometriosis

Islands of endometrium found in the myometrium that may cause the uterus to grow to two to four times its normal size

Adenomyosis

Chocolate cysts

Endometriosis (in ovaries)

Name the tumor of the vulva or vagina associated with each of the following statements:

Eczematous lesion; biopsy shows large cells in epidermis with marginal clearing

Paget disease of vulva. Note: not always associated with underlying adenocarcinoma

Rare, malignant tumor of vagina associated with maternal use of diethylstilbesterol (DBS) during pregnancy

Clear cell adenocarcinoma

Associated with HPV types 16,18, 31, 33, and 45; #1 malignancy of vulva; ↑ in older women

Squamous cell carcinoma of vulva

“Bunch of grapes” protruding from vagina; usually in girls 5-y/o, desmin positive

Sarcoma botryoides

Accounts for 95% of neoplasms of vagina; usually from extension of cervical cancer

Squamous cell carcinoma of vagina

Name the uterine tumor associated with each of the following statements:

Neoplastic changes in the endometrium occurring at squamocolumnar junction; associated with HPV infection

Cervical intraepithelial neoplasia (CIN)

Invasive carcinoma evolving from CIN

Squamous cell carcinoma of the cervix

Very common, benign, estrogen-sensitive smooth muscle tumor of the uterus; usually 20- to 40-y/o

Leiomyoma (fibroid)

Most common gynecologic malignancy; associated with prolonged estrogen exposure; usually 55- to 65-y/o

Endometrial carcinoma

Highly aggressive, bulky tumor with areas of necrosis; arises de novo; ↑ incidence in blacks

Leiomyosarcoma

What HPV types are commonly associated with a high risk of squamous cell carcinoma?

Types 16,18, 31, 33

What are the HPV viral proteins associated with squamous cell carcinoma?

E6 and E7

What role do HPV viral proteins play in the development of invasive cervical carcinoma?

Proteins E6 and E7 bind to and inactivate gene products of p53and Kb,respectively.

What are the distinguishing histopathologic features of carcinoma in situ (CIN 3)?

Atypical changes extending through entire thickness of the epithelium

Name four factors associated with increased risk for invasive cervical carcinoma:

1. Early sexual activity

2. Multiple sex partners

3. ↓ Socioeconomic status

4. Cigarette smoking

What is the most effective screening tool for cervical cancer?

Routine pap smears

Name five factors that predispose to endometrial carcinoma:

1. Nulliparity

2. Obesity

3. Diabetes

4. Unopposed estrogen exposure (eg, estrogen-producing tumors, hormone replacement therapy [HRT])

5. Tamoxifen

How does endometrial carcinoma typically present?

Postmenopausal vaginal bleeding

Name the ovarian cyst associated with each of the following statements:

Distention of unruptured graaf ian follicle; may be associated with ↑ estrogen endometrial hyperplasia

Follicular cyst

Hemorrhage into persistent corpus luteum; menstrual irregularity

Corpus luteum cyst

Due to gonadotropin stimulation; often bilateral/multiple; associated with choriocarcinoma and moles

Theca-lutein cyst

Name the ovarian tumor associated with each of the following statements:

Malignant tumor of epithelial origin; two-thirds are bilateral; psammoma bodies

Serous cystadenocarcinoma

Benign adenoma; frequently bilaterally; lined with fallopian tubelike epithelium

Serous cystadenoma

Malignant GCT that is homologous to seminoma and may occur in childhood

Dysgerminoma

Malignant tumor of epithelial origin; can rupture and cause pseudomyxoma peritonei

Mucinous cystadenocarcinoma

Benign multilocular cyst lined by mucus-secreting epithelium

Mucinous cystadenoma

Benign GCT with elements from multiple embryonic layers; most common GCT

Mature teratoma (dermoid cyst)

Benign tumor; cells resembling bladder transitional epithelium

Brenner tumor

GCT with Schiller-Duval bodies; ↑ AFP

Yolk sac (endodermal sinus) tumor

GCT associated with struma ovarii (mature thyroid tissue)

Teratoma (monodermal)

Malignant, aggressive tumor arising from syncitiotrophoblastic cells; ↑ serum β-hCG

Choriocarcinoma

Stromal tumor associated with Meigs syndrome (ascites, hydrothorax)

Thecoma-fibroma

Benign, estrogen-secreting tumor; Call-Exner bodies

Granulosa-theca tumor

Stromal tumor secreting androgens and causing virilization

Sertoli-Leydig cell tumor

Metastatic tumor from gastric adenocarcinoma; signet ring cells

Krukenberg tumor

Most ovarian carcinomas are associated with an increase in what serologic marker?

CA-125

What two genes are associated with a predisposition to ovarian cancer?

1. BRCA1

2. HNPCC

What is the most common type of ovarian neoplasm in women older than 20 years?

Epithelial cell neoplasms (~75% of all ovarian cancers)

What is the most common type of ovarian neoplasm in women younger than 20 years?

Germ cell neoplasms

Breast Disorders

Name the breast disease associated with each of the following statements:

Benign, firm, painless, rubbery mass; most common tumor 25-y/o

Fibroadenoma

Inflammatory lesion caused by S. aureus;often occurs during nursing

Acute mastitis

”Blue-domed” cysts; usually bilateral; breast tenderness during menstruation

Fibrocystic change

Benign tumor of lactiferous ducts; most common cause of serous or bloody discharge in females 35-y/o

Intraductal papilloma

Large, malignant form of fibroadenoma

Cystosarcoma phyllodes

Invasive, malignant tumor; cells arranged in linear fashion; bloody discharge; often bilateral

Invasive lobular carcinoma

Malignant, firm mass with cells in glands; most common carcinoma of breast

Invasive ductal carcinoma

Eczematous lesion of nipple or areola containing large cells with marginal clearings

Paget disease of the breast

Name six risk factors for breast cancer:

1. Age > 45-y/o

2. Early menarche and late menopause (↑ span of reproductive period)

3. Family history of (1° relative with history of [h/o]) premenopausal breast cancer

4. Personal h/o breast cancer

5. Inherited mutation (eg, HER-2/neu oncogene)

6. Obesity and high animal fat diet

Note: risk is not increased by fibroadenoma or nonhyperplastic cysts.

Which disease is almost always associated with Paget disease of the breast?

Ductal carcinoma in situ

In which quadrant of the breast are most cancers located?

~50% found in upper, outer quadrant

What is the significance of estrogen/progesterone receptors on breast cancer?

Presence of estrogen and progesterone receptors reflects good prognosis (because tumor will likely respond to hormonal therapy).

What is the single most important prognostic factor in breast cancer?

Lymph node involvement (metastatic spread)

What two tumor suppressor genes are associated with a genetic predisposition for breast cancer?

1. BRCA1

2. BRCA2

What is the general function of the BRCA1 and BRCA2 genes?

DNA repair

Trastuzumab (Herceptin) treatment of breast cancers is directed at the protein product of which overexpressed gene?

HER2/neu

Pregnancy

Name the disorder of pregnancy associated with each of the following statements:

An ovum without DNA → “honeycombed uterus” and “cluster of grapes” appearance; formed from intrauterine proliferation of trophoblasts and cystic swelling of chorionic villi; ↑ serum β-hCG

Hydatidiform mole

Tear in placental membranes → sudden peripartal respiratory distress → shock → death

Amniotic fluid embolism

Placental attachment directly to myometrium → impaired separation and massive bleeding at delivery

Placenta accreta

Placental attachment to the lower uterine segment, extending to or obstructing the inner cervical os; painless bleeding in any trimester

Placenta previa

Premature detachment of a normally situated placenta; painful bleeding often in third trimester

Abruptio placentae

Hydatidiform mole with 46, XX genotype and markedly elevated β-hCG; no embryo; paternal chromosomes

Complete mole

Hydatidiform mole with triploid genotype and ↑ β-hCG; fetal parts may be present; (2 sperm + 1 egg)

Incomplete mole

Malignant, aggressive tumor that may arise from mole, ectopic, or normal pregnancy

Gestational choriocarcinoma

Toxemia of pregnancy with triad of HTN, edema, and proteinurea

Preeclampsia

Association with preeclampsia; can lead to death by cerebral hemorrhage or ARDS

Hemolysis, Elevated LFTs,

Low Platelets (HELLP syndrome)

Preeclampsia plus convulsions; DIC may be present

Eclampsia

What are some causes of polyhydramnios (> 1.5-2 L of amniotic fluid)?

Maternal diabetes, esophageal/duodenal atresia, anencephaly, Down syndrome

What are some causes of oligohydramnios (0.5 L of amniotic fluid) and what sequence can result?

Genitourinary obstruction (esp. posterior urethral valves in boys), bilateral renal agenesis; can result in Potter syndrome/sequence

Name the six clinically important and dangerous infections of pregnancy:

“ToRCHeS”

1. Toxoplasma

2. Rubella

3. CMV

4. and 5. HSV and HIV

6. Syphilis

Pituitary Disorders

Name the pituitary disorder associated with each of the following statements:

Most common pituitary adenoma

Prolactinoma (prolactin-secreting adenoma)

Deficiency of GnRH → lack of 2° sexual characteristics; associated with anosmia

Kallmann syndrome

Polyuria, polydipsia, hypernatremia from ↓ ADH; associated with a pituitary or hypothalamic injury

Central/neurogenic diabetes insipidus

Panhypopituitarism 2° to brain tumor, ischemia, or trauma

Simmonds disease. Note: > 75% of cells must be destroyed before clinically evident.

Hypopituitarism caused by postpartum pituitary necrosis

Sheehan syndrome

Somatotrophic adenoma causing excess GH and IGF-1

Acromegaly (adults)/gigantism (kids)

Pituitary hypersecretion of ADH→ hyponatremia, ↓ urine output, mental status changes

Syndrome of inappropriate antidiuretic hormone (SIADH)

What are the most important hormones to replace in Sheehan syndrome or pituitary apoplexy?

Cortisol and thyroid hormones

Name the endocrine/renal disorder associated with the following statements:

↓ sNa, ↑ Uosm with Uosm > Sosm

Syndrome of inappropriate ADH (SIADH)

High-normal sNa, ↑ Sosm, ↓ Uosm but no change in Uosm with H_2O deprivation test

Diabetes insipidus (DI)

Low-normal sNa, ↓ Uosm but ↑ Uosm toward normal w/H_2O deprivation test

Primary polydipsia

What are the two common presentations of a pituitary tumor?

1. Mass effect (bitemporal hemianopia, cranial nerve [CN] palsies)

2. Endocrine effects (amenorrhea, galactorrhea, hyperthyroidism, ↓ libido)

Thyroid

What are the symptoms and physical findings of hypothyroidism?

Cold intolerance, ↓ HR, hypertension, hypercholesterolemia, pericardial effusion, periorbital myxedema, hypoactive deep tendon reflexes, coarse, dry skin; hair loss, weight gain, constipation, amenorrhea, ↓ pitch of voice, depression

What are symptoms and physical findings of hyperthyroidism?

Heat intolerance, hypertension, ↑ CO, ↑ HR, palpitations, cardiomegaly (long-term), staring gaze, lid lag, ↑ sympathetic activity, fine tremor, warm, moist, and flushed skin; fine hair; Graves disease → pretibial myxedema, weight loss despite hyperphagia, ↑ motility, menstrual abnormalities, osteoporosis, anxiety

Name four laboratory findings common in hyperthyroidism:

1. ↓ TSH (in 1°)

2. ↑ free T_4

3. ↑ total T_4

4. ↑ T_3 uptake

Name four laboratory findings common in hypothyroidism:

1. ↑ TSH (very sensitive for 1°)

2. ↓ free T_4

3. ↓ total T_4

4. ↓ T_3 uptake

Name the thyroid disorder associated with each of the following statements:

Child with coarse facial features, short stature, mental retardation, and umbilical hernia

Congenital hypothyroidism (cretinism)

Goiter occurring with high frequency in iodine-deficient areas

Endemic goiter

Painless enlargement of thyroid of autoimmune etiology; Hiirthle cells and germinal centers; hypothyroid

Hashimoto thyroiditis

Triad of diffuse thyroid hyperplasia, ophthalmopathy, dermopathy; hyperthyroid

Graves disease

Normal thyroid replaced by fibrous tissue; hypothyroid

Riedel thyroiditis

Postviral, painful inflammation of thyroid; associated with HLA-B35

Subacute (granulomatous, de Quervain) thyroiditis

Painless goiter that may occur in the postpartum period; lymphocytic infiltrates without germinal centers

Subacute lymphocytic (painless) thyroiditis

Thryoid-stimulating immunoglobluin (TSI) and TSH-receptor antibody (AB)

Graves disease

Thyroid peroxidase antibody

Hashimoto disease

Extreme thyroid enlargement (> 2 kg) causing mass effects; most patients euthyroid

Multinodular goiter

Most common thyroid carcinoma

Papillary carcinoma

Calcitonin-secreting tumor with amyloid deposits

Medullary carcinoma

Biopsy shows “Orphan Annie” nuclei, “fingerlike” projections, and psammoma bodies

Papillary carcinoma

Carcinoma presenting as a single nodule with uniform follicles

Follicular carcinoma

Aggressive carcinoma of older patients with pleomorphic cells; dismal prognosis

Anaplastic (undifferentiated) carcinoma

Carcinoma associated with Hashimoto thyroiditis

Lymphoma

What type of nodules is more likely to be benign: hot or cold?

Hot

Which gene is associated with medullary carcinoma of the thyroid?

RET

What is the function of the two genes associated with papillary carcinoma of the thyroid?

Tyrosine kinase receptors

1. RET

2. NTRK1

Name the multiple endocrine neoplasia (MEN) syndrome characterized by the following features:

Pheochromocytoma, thyroid medullary carcinoma, and parathyroid adenomas

MEN 2 (Sipple syndrome)

Tumors of the pituitary, pancreatic islet cells, and parathyroid gland

MEN 1 (Wermer syndrome)

Mutation of RET oncogene on chromosome lOq

MEN 2

Tumors in MEN 2 plus tall, thin habitus, prominent lips, and ganglioneuromas of the tongue and eyelids

MEN 3 (MEN 2b)

Mutation of MEN 1 gene on chromosome 11 q

MEN1

Autosomal-dominant (AD) inheritance

All MEN syndromes

Parathyroid Disorders

Name the parathyroid disorder associated with each of the following statements:

Caused by chronic renal failure or ↓ vitamin D

2° hyperparathyroidism

Most commonly due to parathyroid adenomas

1° hyperparathyroidism

Etiologies include congenital gland absence, surgically induced, and autoimmune destruction

Hypoparathyroidism

Due to autonomous hormone-secreting adenoma, often occurs after correction of chronic renal failure

3° hyperparathyroidism

Autosomal-recessive (AR) end-organ resistance to PTH → short stature and short third/fourth metacarpals

Pseudohypoparathyroidism

What four systems are primarily targeted by hyperparathyroidism?

1. Painful bones: osteitis fibrosa cystica, osteoporosis

2. Renal stones: nephrolithiasis, nephrocalcinosis

3. Abdominal groans: constipation, peptic ulcer disease (PUD), pancreatitis

4. Psychic moans: depression, lethargy, seizures

Up to 20% of parathyroid adenomas are commonly associated with altered activity of which gene?

PRAD1

Adrenal Disorders

Name the four etiologies for hypercorticism (Gushing syndrome):

1. Exogenous glucocorticoids (most common overall)

2. Pituitary ACTH hypersecretion (eg, adenoma)

3. Hypersecretion of cortisol (eg, adrenal hyperplasia)

4. Paraneoplastic (ectopic) ACTH secretion from a tumor

What is the most common cause of endogenous hypercortisolism?

Cushing syndrome (pituitary adenoma)

What finding specific to an ACTH-producing pituitary adenoma differentiates it from adrenal cortisol-producing and ectopic ACTH-producing tumors?

↓Cortisol level after high-dose dexamethasone suppression test

In most cases of congenital adrenal hyperplasia, deficiency in which enzyme is associated with defective conversion of progesterone to 11-deoxycorticosterone?

21-Hydroxylase

Name nine clinical findings of Gushing syndrome:

1. Hyperglycemia (insulin resistance)

2. Virilization and menstrual irregularities in women

3. Moon facies

4. Truncal obesity

5. Buffalo hump

6. Skin changes (thinning, striae)

7. Osteoporosis

8. Immune suppression

9. Proximal muscle weakness

Name the adrenal disorder associated with each of the following statements:

Aldosterone-secreting adenoma causing HTN and hypokalemic, metabolic alkalosis

Conn syndrome

(1° hyperaldosteronism)

Endotoxin-mediated massive adrenal hemorrhage

Waterhouse-Friderichsen syndrome (N. meningitidis)

Deficiency of aldosterone and cortisol due to adrenal atrophy or destruction

1° chronic adrenocortical insufficiency (Addison disease)

Hypothalemic pituitary axis (HPA) disturbance causing failure of ACTH secretion

2° adrenocortical insufficiency

Bilateral hyperplasia of zona glomerulosa caused by stimulation of renin-angiotensin-aldosterone (RAA) system

2° hyperaldosteronism

Results from rapid steroid withdrawal or sudden ↑ in glucocorticoid requirements

1° acute adrenocortical insufficiency (adrenal crisis)

Chromaffin cell tumor usually in adults; results in episodic hyperadrenergic symptoms

Pheochromocytoma

Malignant, “small blue cell” tumor of medulla in kids associated with N-myc oncogene amplification

Neuroblastoma

How are 1° and 2° adrenocortical insufficiencies differentiated?

Hyperpigmentation is absent in 2° adrenocortical insufficiency (POMC is not increased).

Measurement of what substance can differentiate between 1° and 2° hyperaldosteronism?

Renin (↑ in 2° hyperaldosteronism)

What is the drug of choice for hyperaldosteronism?

Spironolactone (aldosterone antagonist)

What is the “rule of 10’s” for pheochromocytomas?

10% malignant

10% bilateral

10% extra-adrenal

10% pediatric

10% familial

10% calcified

Besides MEN, name three familial syndromes associated with pheochromocytomas:

1. Sturge-Weber syndrome

2. von Recklinghausen syndrome

3. von Hippel-Lindau syndrome

What substances are secreted from pheochromocytomas and how are they detected?

Epinephrine and norepinephrine; detected by ↑ urinary secretion of catecholamines and their metabolites (metanephrine, VMA, and so forth)

Adrenogenital Syndromes

Name the enzyme deficiency responsible for each of the following androgenital syndromes:

↓ Sex hormones, ↓ cortisol, ↑ mineralocorticoids; HTN, hypokalemia, phenotypic female without maturation

17α-Hydroxylase deficiency

↓ Cortisol, aldosterone, and corticosterone; ↑ sex hormones; virilization, HTN

llβ-Hydroxylase deficiency

↓ Cortisol, aldosterone, and corticosterone; ↑ sex hormones; virilization, hypotension, hyperkalemia, “salt wasting”

21-Hydroxylase deficiency

What is the phenotypic result of androgen insensitivity syndrome (testicular feminization)?

“Hairless woman”; XY with undescended testes but female/ambiguous genitalia

List the three syndromes associated with 21-hydroxylase deficiency:

1. Salt-wasting adrenogenitalism

2. Simple virilization adrenogenitalism (ambiguity and adrenal hyperplasia)

3. Asymptomatic

Diabetes

Describe the acute presentation of type 1 diabetes niellitus (DM).

Polydipsia, polyuria, polyphagia, weight loss, and diabetic ketoacidosis (DKA) if extreme

What causes hyperglycemia in type 1 DM?

Lack of insulin from decreased β-cell mass

What is the proposed mechanism of islet cell destruction in type 1 DM?

Environmental triggering of autoimmunity to islet β-cells

What is the theorized cause of type 2 DM?

Obesity increases insulin resistance and causes derangement of β-cell insulin secretion.

What are three ways to diagnose DM?

1. Fasting serum glucose > 126 (100-126 = impaired fasting glucose)

2. Oral glucose tolerance test > 200 (148-200 = impaired glucose tolerance)

3. Symptoms + random glucose > 200

What is HbA1c and what is it used for?

Percent of glycosylated hemoglobin in blood; correlates with glycemic control over the last 90 to 120 days

Type 1 or type 2 DM?

Relatively common in the US population

Type 2

Younger average age of onset

Type 1

Strong, polygenic predisposition

Type 2

Associated with obesity

Type 2

Insulin treatment required from the time of diagnosis

Type 1

Associated with HLA-DR3 and -DR4

Type 1

May present with hyperosmolar coma

Type 2

May present initially as DKA

Type 1

Amyloid deposition in the islets

Type 2

What two cleavage products of proinsulin are stored in the granules of β-islet cells?

1. Insulin

2. C-peptide

Which membrane protein mediates glucose uptake by β-islet cells?

GLUT-2

Increased cytoplasmic concentration of which ion stimulates the secretion of insulin?

Calcium

By what mechanism is the cytoplasmic concentration of calcium increased in β-cells following uptake of glucose?

Decreased activation of adenosine triphosphate (ATP)-sensitive potassium channels leads to membrane depolarization, resulting in an influx of extracellular calcium via a voltage-dependent calcium channel.

Glucose uptake in which organ is independent of insulin?

The brain

What signal transduction pathway mediates the mitogenic effects of insulin binding?

MAP-kinase pathway

Activation of the PI-3K signal transduction pathway by insulin results in the translocation of what molecule to the surface of myocytes in order to transport glucose into myocytes?

GLUT-4

List four potential effects of advanced glycation end products (AGEs) in type 1 diabetes:

1. Cross-linking of collagen

2. Accumulation of extracellular matrix proteins resistant to proteolytic degradation

3. Generation of reactive oxygen species

4. NF-κB activation

What is the most common cause of death in diabetics?

Myocardial infarction (MI) due to accelerated atherosclerosis

What is the most common morphologic change in the microvasculature of a diabetic?

Diffuse thickening of the basement membrane

Describe the long-term effect(s) of DM on each of the f ollowing organ systems:

Cardiovascular (large vessels)

Atherosclerosis → cerebrovascular accident (CVA), MI, peripheral vascular disease (PVD)

Renal/urinary

Glomerular: glomerulosclerosis, proteinuria

Vascular: arteriosclerosis → HTN, chronic renal failure

Infectious: UTIs, pyelonephritis, necrotizing papillitis

Nervous

Motor and sensory peripheral neuropathy, autonomic degeneration

Eye

Retinopathy, cataract formation

Skin

Xanthomas, cutaneous infections, poor wound healing, fungal infections

Name four causes of 2° DM:

1. Pancreatic disease (eg, hemochromatosis, pancreatitis, pancreatic carcinoma)

2. Pregnancy (gestational diabetes)

3. Gushing syndrome

4. Other endocrine disorders (eg, acromegaly, glucagonoma, hyperthyroidism)

Pancreatic Endocrine Tumors

Name the islet cell tumor associated with each of the following statements:

Most common islet cell tumor

Insulinoma (β-cell tumor)

2° DM, necrolytic migratory erythema

Glucagonoma (α-cell tumor)

Associated with Zollinger-Ellison syndrome

Gastrinoma

Associated with watery diarrhea, hypokalemia, and achlorhydria (WDHA) syndrome

VIPoma

2° DM, cholelithiasis, steatorrhea

Somatostatinoma (δ-cell tumor)

Clinically characterized by Whipple triad

Insulinoma (β-cell tumor)

Name the clinical findings of Whipple triad:

Hypoglycemia, concurrent central nervous system (CNS) dysfunction, and reversal of symptoms with glucose

What is Zollinger-Ellison syndrome?

Hypersecretion of gastric HC1, recurrent PUD, and hypergastinemia

PHARMACOLOGY

Pituitary

For each of the following drugs, provide:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects and uniquetoxicity (TOX) (if any)

Octreotide

MOA: somatostatin analog

IND: acromegaly, secretory diarrhea from VIPoma, carcinoid symptoms, high-output fistulas

Leuprolide

MOA: GnRH analog. Note: given pulsatile = agonist; given continuous = antagonist

IND: continuous →prostate cancer, endometriosis, uterine fibroids. Pulsatile → infertility

TOX: antiandrogenic effects, nausea, vomiting

Oxytocin

MOA: ↑ uterine contraction

IND: induce/reinforce labor; control uterine hemorrhage

TOX: uterine rupture, hypertensive crisis

Desmopressin

MOA: vasopressin analog

IND: central diabetes insipidus, nocturnal enuresis

TOX: HTN, overhydration, coronary constriction

Thyroid and Parathyroid

For each of the f ollowing drugs, provide:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects and uniquetoxicity (TOX) (if any)

Levothyroxine (T_4)

MOA: synthetic T_4 → converted to T_3

IND: hypothyroidism (maintenance replacement)

TOX: nervousness, palpitations, ↑ HR, heat intolerance

Propylthiouracil/methimazole

MOA: blocks thyroid peroxidase, propylthiouracil also ↓ peripheral conversion of T_4 → T_3

IND: hyperthyroidism (propylthiouracil okay in pregnancy)

TOX: rash, agranulocytosis (rare), +ANCA vasculitis, hepatotoxicity, lupuslike syndrome

Risedronate

MOA: bisphophonate (inhibits osteoclastic function)

IND: osteoporosis, Paget disease, metastatic bone cancer, hyperparathyroidism

TOX: GI upset, esophagits

Calcitonin

MOA: ↓ bone resorption, ↓ serum Ca2+and phosphate

IND: acute hypercalcemia, Paget disease, osteoporosis

Which other drug is used to treat the symptoms of hyperthyroidism?

Propanolol (β-blocker)

Diabetes

Sulfonylureas (eg, tolbutamide, glyburide, chlorpropamide)

MOA: pancreas, closes K+ channels in (β-cell membrane → depolarization → ↑ Ca2+ influx → insulin release

IND: type 2 diabetes (not used in type 1 because it requires some residual (β-cell activity)

TOX: hypoglycemia, weight gain

Metformin (Glucophage)

MOA: liver, ↓ gluconeogenesis; ↑ glycolysis; ↓ postprandial glucose

IND: newly diagnosed diabetic (no islet cell function required)

TOX: potentially life-threatening lactic acidosis, ↓ vitamin B_12 absorption, contraindicated in renal insufficiency

Glitazones (eg, rosiglitazone, pioglitazone)

MOA: ↑ target cell response to insulin

IND: type 2 diabetes (monotherapy or combination)

TOX: hepatotoxicity (troglitazone), upper respiratory infection (URI), weight gain, edema, congestive heart failure, and anemia (rosiglitazone)

α-Glucosidase inhibitor (eg, acarbose)

MOA: inhibits α-glucosidase at brush border → ↑ glucose absorption

IND: type 2 diabetes

TOX: GI upset (flatulence, diarrhea)

Insulin

MOA: tyrosine kinase activity →↑ glycogen and protein synthesis, triglyceride (TG) storage, and K+ uptake

IND: type 1 and refractory type 2 diabetes; life-threatening hyperkalemia

TOX: hypoglycemia and rare hypersensitivity reaction

For each of the following types of insulin, state the peak and duration of action:

Insulin lispro

Peak = 30 to 60 minutes; duration = 3 to 4 hours

NPH insulin

Peak = 8 to 12 hours; duration = 18 to 24 hours

Lente insulin

Peak = 8 to 12 hours; duration = 18 to 24 hours

Ultralente insulin

Peak = 8 to 16 hours; duration = 18 to 28 hours

Insulin glargine

Peak = none (peakless); duration 20 to 24+ hours

Adrenal Gland

Describe the mechanism of action of corticosteroids:

Corticosteroids bind to cytoplasmic receptors, pass into the nucleus complexed with their receptors, and act as transcription factors for specific target genes.

How do glucocorticoids affect arachidonic acid metabolism?

Glucocorticoids inhibit phospholipase A2, blocking the release of arachidonic acid and ↓ production of prostaglandins and leukotrienes.

Select the most appropriate corticosteroid for each of the following clinical situations:

Diagnosis of Gushing syndrome

Dexamethasone

Autoimmune disorder

Prednisone

Addison disease

Hydrocortisone (+/- fludrocortisone)

Relief of inflammation

Prednisone, cortisone

Asthma/allergies

Beclomethasone or triamcinolone aerosol

Used to ↑ fetal lung maturity

Betamethasone

Cancer chemotherapy

Prednisone

List the effect of glucocorticoids on each of the f ollowing systems:

Metabolic

↑ Gluconeogenesis; net ↑ in fat deposition in prototypical areas

Muscle

↑ Muscle protein catabolism; myopathy → weakness

Bone

↑ Bone catabolism

Immune

Inhibits cell-mediated immunity; ↑ PMNs; ↓ lymphocytes, basophils, eosinophils, and monocytes; ↓ leukocyte migration

Psych

Behavioral changes, psychoses

GI

↓ Resistance to ulcers

Vascular

↓ Capillary permeability →↓ edema at sites of inflammation

What is the consequence of abrupt discontinuation of corticosteroid use?

Acute adrenal insufficiency syndrome (potentially lethal)

Name eight commonly observed effects of long-term corticosteroid use:

1. Osteoporosis

2. HTN

3. Insulin resistance

4. Edema

5. Psychoses

6. Peptic ulcers

7. ↑ Susceptibility to infections

8. Cataracts

What classic toxicity is associated with excess corticosteroid use?

latrogenic Gushing syndrome

For each of the following drugs, provide:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects and uniquetoxicity (TOX) (if any)

Spironolactone

MOA: spironolactone binds estrogen receptors

IND: hirsutism (eg, in PCOS), prostate/breast cancer

TOX: gynecomastia, thrombocytopenia, hepatotoxicity

Clomiphene

MOA: blocks negative feedback → ↑ GnRH →↑ LH and FSH → ovulation

IND: infertility

TOX: ovarian enlargement, multiple births, hot flashes

Tamoxifen

MOA: competes for estrogen receptors → blocks binding to ER ⊕ cells

IND: breast cancer

TOX: ↑ risk of endometrial carcinoma, hot flashes

Finasteride

MOA: 5α-reductase inhibitor →↓ DHT

IND: benign prostatic hyperplasia (BPH), hair loss

TOX: impotence, gynecomastia

Flutamide

MOA: competitive androgen receptor blocker

IND: prostatic carcinoma

Mifepristone (RU486)

MOA: competitive progesterone receptor blocker

IND: abortion

TOX: GI upset, metrorrhagia

Dinoprostone

MOA: PGE_2 analog causes cervical dilation and uterine contraction

IND: induction of labor; abortion

Ritodrine, terbutaline

MOA: β_2-agonists relax the uterus

IND: preterm labor

TOX: maternal and fetal tachycardia, fluid retention, and hyperglycemia

Sildenafil, vardenafil

MOA: inhibits phosphodiesterase type 5 →↑ cGMP → smooth muscle relaxation of corpus cavernosum

IND: erectile dysfunction

TOX: hypotension if also taking a nitrate, priapism, headache, color vision changes

Name five benefits of oral contraceptives (OCPs):

1. ↓ Risk of ovarian and endometrial cancer

2. ↓ Genitourinary infections

3. Regulates menstrual cycle

4. Low failure rate (if taken appropriately)

5. ↓ Risk of ectopic pregnancy

Name five disadvantages of OCPs:

1. Requires daily pill ingestion

2. Not protective against STDs

3. ↑ Triglycerides

4. ↑ Risk of hepatic adenoma

5. Induces hypercoagulable state

Name four contraindications to OCPs:

1. Pregnancy

2. H/o thromboembolism or stroke

3. H/o breast cancer or endometrial cancer

4. Smoking (in women > 35-y/o)

CHAPTER 9

Renal and Genitourinary

EMBRYOLOGY

Name the structure(s) derived from each of the following:

Nephrogenic cord (three structures)

1. Pronephros

2. Mesonephros

3. Metanephros

Ureteric bud

C CUP (”see you pee”): Collecting tubules, Calyces, Ureter, Pelvis

Genital Ridge

Gonads

Reproductive structures from the mesonephric (Wolffian) duct

”SEED” (in males only):Seminal vesicles, Epididymis, Ejaculatory duct, Ductus deferens

Reproductive structures from the paramesonephric (Miillerian) duct

In women only:Fallopian tubes, uterus, superior portion of vagina

Metanephros

Definitive adult kidney

Name the embryologic tissue layer that following components of the genitourinary system develop from:

Kidneys (ie, nephrons)

Mesoderm (intermediate mesoderm)

Collecting tubules, calyces, pelvis, ureters

Mesoderm (intermediate mesoderm)

Bladder, urethra

Endoderm (cloaca)

Name the parts of the external genitalia in males and females derived from the following embryologic structures:

Genital tubercle

Males: glans penis; females: glans clitoris

Urogenital sinus

Males: corpus spongiosum, bulbourethral (Cowper) glands, prostate gland; females: vestibular bulbs, Bartholin and Skene glands

Urogenital folds

Males: ventral shaft of penis; females: labia minora

Labioscrotal swelling

Males: scrotum; females: labia majora

Describe the following congenital disorders:

Exstrophy of the bladder

Congenital defect in the anterior wall of the bladder and adjacent abdominal wall causing the bladder to be exposed at birth; associated with epispadias

Horseshoe kidney

Fusion of the lower (or upper) poles of kidneys → kidney fails to ascend → often malrotated and remains in pelvis

Hypospadias

Penile abnormality resulting in urethra opening on the ventral (inferior) side of penis; most common congenital penile abnormality

Epispadias

Penile abnormality resulting in urethral opening on the dorsal (superior) side of penis; associated with bladder exstrophy

Renal agenesis

Results from failure of the ureteric bud to form; associated with Potter syndrome

Potter syndrome

Renal agenesis → oligohydramnios → limb deformities and pulmonary hypoplasia

What structure limits the ascent of a fused horseshoe kidney?

Inferior mesenteric artery

What substance secreted by the testes

Suppresses development of paramesonephric ducts in males?

Müler ian-inhibiting substance

Promotes development of the mesonephric ducts?

Fetal androgens

Describe the gonads and external genitalia of the following:

Female (XX) infant with congenital adrenal hyperplasia (CAH)

Female gonads with masculinized genitalia

Male (XY) infant with androgen-insensitivity syndrome

Male gonads with female external genitalia, but no uterus or fallopian tubes

ANATOMY

Name the structures contained in the retroperitoneal space:

Ureters, kidneys, adrenals, pancreas, duodenum (2nd, 3rd, and 4th parts), ascending/descending colon, rectum, aorta, IVC

What is the approximate vertebral level of the kidneys?

T12 to L3 (The right kidney is slightly lower because of liver.)

Name the renal blood vessel that runs posterior to the superior mesenteric artery (SMA) and anterior to the aorta:

Left renal vein

What vessel does the left gonadal vein drain into?

Left renal vein

What important structures do the ureters pass under on their way to the bladder?

Females: uterine artery; males: ductus deferens; water (ureters) under the bridge (uterine artery, ductus deferens)

Which terminal vessels carry blood toward the glomerulus?

Afferent arterioles

What specialized cells are found between the afferent and efferent glomerular arterioles and have receptors for angiotensin II (AT II) and atrial natriuretic peptide (ANP)?

Lacis cells (extraglomerular mesangial cells)

What makes up the juxtaglomerular apparatus (JGA)?

JG cells, lacis cells, and the macula densa

What hormone do the JG cells secrete?

Renin

What anatomic feature makes stress incontinence more common in women?

External urethral sphincter does not completely surround female urethra.

Name the sensory and motor components of the micturition reflex:

Pelvic splanchnic nerves (parasympathetic S2-S4)

PHYSIOLOGY

What percentage of body weight is total body water (TBW)?

~60%

What proportion of TBW is accounted for by intracellular fluid (ICF) and extracellular fluid (ECF)?

Two-thirds ICF, one-third ECF (60 = 40 + 20. Rule: 40% body weight is ICF, 20% is ECF.)

Name the major cations and anions found in ICF:

Cations = K+, Mg2+; anions = proteins, organophosphates (eg, ADP, ATP)

Name the major cations and anions found in ECF:

Cations = Na+; anions = CF, HCO−3

What are the relative proportions of plasma and interstitial fluid in ECF?

One-fourth plasma volume, three-fourths interstitial volume

What is considered normal ECF osmolality?

~290 mOsm

Clearance of what chemical can be used to measure glomerular filtration rate (GFR)?

Inulin (Inulin is freely filtered, but neither secreted nor reabsorbed.)

What is a useful clinical measure to estimate GFR?

Creatinine clearance

What is considered normal GFR?

~120 mL/min

Effective renal plasma flow (ERPF) can be measured by calculating the clearance of what substance?

Para-aminohippuric acid (PAH). PAH is filtered and secreted.

Complete the following calculations:

UxV/Px (urine concentration X urine volume/plasma concentration) =

Renal clearance (Cx)

ERPF/(1 - hematocrit) =

Renal blood flow (RBF)

GFR/RPF (renal plasma flow) =

Filtration fraction (FF)

GFR × (plasmax) =

Filtered load

Vurine flow − (Uosm V/Posm) =

Free water clearance

Define GFR using the Starling formula.

Kf[(PGC − PBS) − (πGC − πBS)], where Kf = filtration coefficient, GC = glomerular capillary, BS = Bowman space

List the three components of the glomerular filtration barrier:

1. Fused basement membrane (negative charge barrier)

2. Fenestrated capillary endothelium (size barrier)

3. Epithelial or podocyte foot process layer

If Cx > GFR then there is net ...

tubular secretion of substance X

If Cx

tubular absorption of substance X

If Cv = GFR then there is ...

no net tubular absorption or secretion of substance X

What proportion of total cardiac output does RBF account for?

~25%

How is RBF maintained at a constant level?

Autoregulation (via myogenic response to stretch and the activity of the JGA)

How do the following substances affect the renal arterioles, RPF, GFR, and FF?

Prostaglandins

Prostaglandins dilate afferent arterioles: ↑ RPF, ↑ GFR, thus FF stays constant

AT II

AT II constricts efferent arterioles: ↓ RPF, ↑ GFR, thus FF increases

What effect do the following have on RPF, GFR, and FF?

Afferent arteriole constriction

Decreased RPF and GFR, no change in FF

Efferent arteriole constriction

Decreased RPF, increased GFR, increased FF

Increased plasma protein concentration

No change in RPF, decreased GFR andFF

Decreased plasma protein concentration

No change in RPF, increased GFR andFF

What is the maximum plasma glucose concentration at which glucose will no longer be reabsorbed?

~200 to 250 mg/dL (Concentrations of > 250 mg/dL glucose will be lost in the urine.)

What is the transport maximum (Tm)) for glucose?

At 350 mg/min, carriers are saturated (Tm = renal threshold/GFR).

What factors cause K+ to shift out of cells?

↓ Insulin, (β-blockers, acidosis, digitalis, extreme exercise, cell lysis, hyperosmolarity

What factors cause K+ to shift into cells?

Insulin, (β-agonists, alkalosis

List four causes of decreased distal K+ secretion:

1. Low-K+ diet

2. Hypoaldosteronism

3. Acidosis

4. K+-sparing diuretics

List six causes of increased distal K+ secretion:

1. High-K+ diet

2. Hyperaldosteronism

3. Alkalosis

4. Thiazide diuretics

5. Loop diuretics

6. Luminal anions

Describe a clinical scenario which might lead to each of the following physiologic changes:

Isosmotic volume contraction

Diarrhea

Isosmotic volume expansion

Isotonic fluid infusion (eg, normal saline IV)

Hyperosmotic volume contraction (two scenarios)

1. Profuse sweating

2. Diabetes insipidus

Hyperosmotic volume expansion

High NaCl intake, infusion of hypertonic saline

Hypo-osmotic volume contraction

Adrenal insufficiency (hypoaldosteronism)

Hypo-osmotic volume expansion

Syndrome of inappropriate antidiuretic hormone (SIADH)

FUNCTIONAL REGIONS OF THE NEPHRON

Name the part of the nephron where each of the following processes occur:

Site of reabsorption of all glucose and amino acids, and the majority of bicarbonate, sodium, and water

Proximal convoluted tubule (PCT)

Site of active reabsorption K+, Na+, Cl−

Thick ascending loop of Henle

Site of 50% of urea reabsorption

PCT (passively)

Site of active reabsorption of Na+, Cl-

Early distal convoluted tubule (DCT)

Site of action of thiazide diuretics

DCT

Site of action of K+-sparing diuretics

Collecting tubules

Sections that are impermeable to water

Thick ascending loop of Henle, collecting ducts (in absence of ADH)

Site where ammonia is excreted to act as a buffer for secreted H+ ions

PCT

Portion of the nephron which is impermeable to Na+ and passively reabsorbs water

Thin descending loop of Henle

Aldosterone-sensitive site where Na+ is exchanged for K+ or H+

Collecting tubules

Site of active Ca2+ reabsorption that is controlled by PTH

Early DCT

Site of action of loop diuretics

Thick ascending loop of Henle

Section where reabsorption of water is regulated by vasopressin (ADH)

Collecting tubules

Site of action of carbonic anhydrase inhibitors

PCT

Section which contains principal cells and intercalated cells

Collecting tubules

Site of 85% of all phosphate reabsorption (via cotransport)

PCT

ENDOCRINE FUNCTIONS OF THE KIDNEYS

List the four main endocrine functions of the kidneys:

1. PTH-mediated conversion of 25-OH vitamin D to 1, 25-OH vitamin D by 1α-hydroxylase

2. Secretion of renin by JG cells in response to arterial pressure changes and in response to Na+ and Cl- delivery to the macula densa

3. Secretion of prostaglandins (to increase GFR by dilating afferent arteriole)

4. Secretion of erythropoeitin in response to hypoxia by peritubular endothelial cells

Name the effect of each of the following on the kidneys:

ANP

↓ Na+ reabsorption, ↑ GFR

Aldosterone

↑ Na+ reabsorption, ↑ K+ secretion, ↑ H+ secretion in collecting tubule

Vasopressin (ADH)

↑ Na+/K+/2Cl- transporters in thick ascending limb, ↑ water permeability in principal cells (via aquaporins), ↑ urea absorption in collecting duct

Where is angiotensin-converting enzyme (ACE) primarily found?

Lung capillaries

Briefly describe the renin-angiotensin-aldosterone cascade:

↓ BP (↓ stretch of cells in afferent arterioles) → secretion of renin → conversion of angiotensinogen to angiotensin I (AT I) → AT I converted to AT II by ACE

What is the function of AT II?

Increases intravascular volume and ↑ vascular tone → ↑ BP

Name six specific actions of AT II:

1. Causes potent vasoconstriction

2. Releases vasopressin and adrenocorticotropic hormone (ACTH) from the pituitary

3. Promotes release of aldosterone from adrenal cortex

4. Stimulates hypothalamus to increase thirst

5. Stimulates catecholamine release from the adrenal medulla

6. Increases Na+ and HCO_3- reabsorption in proximal tubule

What cells in the kidneys produce and secrete erythropoietin?

Peritubular capillary cells

What stimulates erythropoietin production and release?

Hypoxia

PATHOLOGY

Polycystic Kidney Disease

Name the disease characterized by multiple 3 to 4 cm renal cysts, bilateral enlargement of the kidneys, and chronic renal failure in adults:

Autosomal dominant (adult) polycystic kidney disease (ADPKD)

What are the signs and symptoms of ADPKD?

Flank pain, hypertension, hematuria, and UTI

Which gene is most commonly associated with ADPKD?

PKD1 (85% of cases)

Name three extra renal manifestations of ADPKD:

1. Liver cysts (40%)

2. Berry aneurysms (10%-30%)

3. Mitral valve prolapse (25%)

What is the prognosis of patients with autosomal recessive polycystic kidney disease (ARPKD)?

Poor; majority die in infancy or early childhood

What type of renal lesions are characteristic of ARPKD?

Multiple cylindrical cysts found perpendicular to cortex in an enlarged kidney

Which of the cystic renal diseases is associated with an increased risk of renal cell carcinoma?

Dialysis-associated cystic disease

Nephrotic and Nephritic Syndromes

What are the classic features of the following:

Nephrotic syndrome

Massive proteinuria (>3.5 g/d), hypoalbuminemia, hyperlipidemia, edema

Nephritic syndrome

Hypertension, azotemia, RBC casts, oliguria, hematuria

Glomerulonephropathies

What term describes the type of immune deposits found outside of the glomerular BM (GBM) but within the podocytes?

Subepithelial

What term describes the type of immune deposits found outside the endothelium but inside the GBM?

Subendothelial

Name the immunof luorescence pattern of deposition of immunoglobulins and/or complement associated with the following diseases:

Membranous glomerulonephritis (GN)

Granular or “starry-sky”

Goodpasture syndrome

Linear

IgA nephropathy (Berger disease)

Mesangial

Poststreptococcal

Granular or “starry-sky”

Name the electron microscopic (EM) appearance of the immunoglobulin and/or complement deposits in the following diseases:

Membranous GN

“Spike and dome” subepithelial deposits

Membranoproliferative GN (MPGN)

Subendothelial humps, “tram track”

Poststreptococcal GN

Subepithelial humps

Name the glomerulopathy most closely associated with each of the following statements:

X-linked syndrome of glomerulonephritis, lens dislocation, nerve deafness, and posterior cataracts

Alport syndrome

Nodular glomerulosclerosis, glomerular capillary basement membrane thickening

Diabetic glomerulosclerosis (Kimmelstiel-Wilson disease)

Commonly associated with HIV infection, heroin abuse, sickle cell disease, and obesity

Focal-segmental glomerulonephritis (FSGN)

Diffuse loss of foot processes of the visceral epithelial cells on EM, but normal appearance on light microscopy

Minimal change disease (lipoid nephrosis)

Apple green birefringence on Congo red stain

Amyloidosis

C-ANCA

Wegener granulomatosis

Most common cause of nephrotic syndrome in kids

Minimal change disease (lipoid nephrosis)

Electron dense deposits in the GBM proper and autoantibody to C3 nephritic factor

MPGN type II (aka dense deposit disease)

Crescents seen in glomeruli on light microscopy

Rapidly progressive glomerulonephritis (RPGN)

Most common cause of end-stage renal disease

Diabetic glomerulosclerosis

Basement membrane thickening and splitting (train tracks)

MPGN type I

Syndrome of hematuria and hemoptysis caused by anti-GBM antibodies

Goodpasture syndrome

Mesangial widening, recurrent hematuria, and proteinuria

Ig A nephropathy

Associated with hepatitis C

MPGN

Responds well to steroids

Minimal change disease (aka steroid responsive nephropathy)

X-linked recessive defect in collagen type IV

Alport syndrome

Asymptomatic familial hematuria

Thin membrane disease (GBM is only 50%-60% of normal thickness.)

“Wire loop lesions”

Systemic lupus erythematosus (SLE)— lupus nephropathy (diffuse proliferative pattern)

Henoch-Schönlein purpura

IgA nephropathy

Irregularly thick GBM with splitting of lamina densa seen on EM

Alport syndrome

Upper respiratory vasculitis and granulomas

Wegener granulomatosis

Renal Tubular Acidosis

Name the type of renal tubular acidosis (RTA) associated with the following statements:

Decreased bicarbonate reabsorption

Type II (proximal)

Dysfunction of principal cells

Type IV

Decreased acidification and acid excretion

Type I (distal)

Hyperkalemia

Type IV

Nongap metabolic acidosis

Types I, II, IV

Fanconi syndrome

Type II (proximal)

Aldosterone deficiency/resistance

Type IV

Most common RTA

Type IV

Acid-Base Disturbances

Name the simple acid/base disturbance and the associated compensatory response:

pH > 7.4, Pco_2 > 40 mm Hg

Metabolic alkalosis → hypoventilation

pH 7.4, Pco_2 > 40 mm Hg

Respiratory acidosis → renal HCO_3- reabsorption

pH > 7.4, Pco_2 40 mm Hg

Respiratory alkalosis → renal HCO_3- secretion

pH 7.4, Pco_2 40 mm Hg

Metabolic acidosis → hyperventilation

What is the formula for calculating anion gap?

Na+ - (Cl- + HCO-3)

What is a normal anion gap range?

8 to 12 mEq/L

List three common causes of nongap metabolic acidosis:

1. Diarrhea

2. Renal tubular acidosis

3. Hyperchloremia

Name the most common cause of respiratory acidosis:

Hypoventilation (which can be caused by acute/chronic lung disease, sedatives, weakening of respiratory muscles)

List three common causes of respiratory alkalosis:

1. Hyperventilation

2. Early aspirin ingestion

3. Gram-negative sepsis

List five common causes of metabolic alkalosis:

1. Excessive vomiting

2. Diuretic abuse

3. Antacid use

4. Hyperaldosteronism

5. Gushing syndrome

List nine possible causes of anion gap metabolic acidosis:

“MUD FILERS”

1. Methanol

2. Uremia

3. Diabetic ketoacidosis

4. Paraldehyde

5. Isoniazid (INH) or Iron tablet overdose

6. Lactic acidosis

7. Ethylene glycol or Ethanol

8. Rhabdomyolysis (massive)

9. Salicylate toxicity

Acute Renal Failure

List the three main types of acute renal failure (ARF):

1. Prerenal

2. Intrinsic

3. Postrenal

List four common prerenal causes of ARF:

1. Hypovolemia

2. Decreased RBF (eg, decreased cardiac output, renal artery stenosis)

3. High peripheral vascular resistance

4. Drugs (eg, diuretics, NSAIDs)

List five common causes of intrinsic ARF:

1. Acute tubular necrosis (ischemic, nephrotoxic, sepsis)

2. Acute glomerulonephritis

3. Autoimmune vasculitis (eg, lupus, scleroderma)

4. Interstitial nephritis

5. Hemolytic uremic syndrome (children)

What is the general mechanism for the development of postrenal ARF?

Any outflow obstruction (benign prostatic hyperplasia [BPH], bladder-neck, stones, prior gynecologic surgery, bilateral ureteric). Note: postrenal ARF accounts for 5% of all causes of ARE

Name the type of ARF associated with each of the following:

Oliguria and FeNa 1%

Prerenal

Oliguria and FeNa > 1%

Intrinsic

Hyaline urine casts

Prerenal

Muddy brown/granular casts

Intrinsic (muddy brown casts are particularly associated with ATN)

Blood urea nitrogen (BUN): creatinine ratio > 20

Prerenal

Urine osmolality > 500 mOsm

Prerenal

List the effects of uremia on each of the f ollowing organs or systems:

Nervous system

Asterixis, confusion, seizures, coma

Cardiovascular system

Fibrinous pericarditis

Hematologic system

Coagulopathy, immunosuppression

Gastrointestinal system

Nausea, vomiting, gastritis

Skin

Pruritis

Endocrine system

Glucose intolerance

List six nonuremic complications of renal failure:

1. Metabolic acidosis

2. Hyperkalemia → arrhythmias

3. Na+ and H_2O excess → pulmonary edema and congestive heart failure (CHF)

4. Hypocalcemia → osteodystrophy (from failure to secrete active vitamin D)

5. Anemia (↓ EPO secretion)

6. Hypertension (from renin hypersecretion)

Which type of ATN often causes GBM rupture?

Ischemic

What substances cause direct injury to the proximal tubules?

Nephrotoxins: drugs (aminoglycosides), toxins, and massive amounts of myoglobin (typically in the setting of a crush injury or strenuous exercise)

Renal Infections

What infection commonly presents with flank pain, costovertebral angle tenderness, fever, dysuria, pyuria, bacteriuria?

Acute pyelonephritis

What are the two major causes of pyelonephritis?

1. Ascending infection

2. Hematogenous seeding

What are the most common organisms responsible for acute pyelonephritis?

Escherichia coli (most common), Proteus, Klebsiella, Enterobacter, Pseudomonas. (Think enteric gram-negative rods.)

What is the greatest risk factor for pyelonephritis?

Vesicoureteric reflux (or incompetence)

List five possible sequelae of acute pyelonephritis:

1. Abscess

2. Necrotizing papillitis

3. Renal scars

4. Perinephric abscess

5. Pyonephrosis

What condition is characterized by broad renal scarring, deformed calyces, progressive loss of renal parenchyma, and thyroidization of kidneys?

Chronic pyelonephritis

What finding on microscopic examination of urine is pathognomonic for pyelonephritis?

WBC casts

Tubulointerstitial Diseases

Name the tubulointerstitial disease associated with each of the following clinical scenarios:

Abuse of phenacetin-containing compounds

Renal papillary necrosis

Penicillin and NSAID use; associated with eosinophilia

Interstitial nephritis

AR syndrome characterized by dysfunction of proximal tubules, leading to impaired reabsorption of amino acids, glucose, phosphate, and bicarbonate

Fanconi syndrome

AR disease characterized by impaired tryptophan reabsorption; clinically resembles pellagra

Hartnup disease

AR syndrome characterized by impaired active chloride reabsorption in the loop of Henle; clinically mimics the actions of loop diuretics

Bartter syndrome

Name the five diseases associated with renal papillary necrosis:

1. Diabetes mellitus

2. Acute pyelonephritis

3. Analgesic nephropathy

4. Sickle cell disease

5. Urinary tract obstruction

Renal Vascular Disease

Name the renal vascular pathology associated with each of the following statements:

Macroscopically, kidneys have a fine granular surface; hyaline arteriolosclerosis, interstitial f ibrosis, glomerular sclerosis

Benign nephrosclerosis

Hyperplastic arteriolitis (onion skinning); presents with diastolic BP > 130, encephalopathy, proteinuria, hematuria, and papilledema

Malignant nephrosclerosis

Pediatric syndrome characterized by ARF, microangiopathic hemolytic anemia, thrombocytopenia, and hypertension

Classic hemolytic-uremic syndrome (HUS)

Syndrome characterized by ARF, microangiopathic hemolytic anemia, hypertension, fever, and mental status changes; associated with ADAMTS-13 defect

Thrombotic thrombocytopenic purpura (TIP)

What is the most common cause of HUS?

Escherichia coliO157:H7 (75% of cases)

What three groups of patients are at increased risk of developing renal failure from benign nephrosclerosis?

1. African Americans

2. Diabetics

3. Patients with hypertension

What type of infarction typically occurs in the kidneys?

”White,” due to end-organ type arterial supply of kidneys

What conditions are associated with diffuse cortical necrosis?

Obstetric catastrophes (eg, severe placental abruption) and septic shock

Name two major causes of renal artery stenosis (RAS):

1. Atherosclerosis (70%)

2. Fibromuscular dysplasia (30%)

What group of people are most likely to have secondary hypertension due to f ibromuscular dysplasia-induced RAS?

Women in their 20’s and 30’s

Urolithiasis

Name the type of renal calculi associated with each of the following statements:

Radiopaque (two types)

1. Calcium stones

2. Struvite stones

Staghorn calculi

Struvite (aka ammonium magnesium phosphate)

Infection with urease-positive bacteria

Struvite (think Proteus)

Most common type of calculus

Calcium

Gout (or any other hyperuricemic condition)

Uric acid stones

Elevated PTH

Calcium

Secondary to inherited defect of amino acid transporter

Cystine (due to cystinuria)

What are the signs and symptoms associated with urinary stone disease?

Renal colic (flank pain radiating to groin), hematuria, and pyelonephritis

Renal and Urinary Tract Tumors

What must be ruled out in an older adult with hematuria?

Urinary tract malignancies (renal and bladder)

Name the renal or urinary neoplasm associated with each of the following statements:

Large, palpable flank mass in a toddler

Wilms tumor (aka nephroblastoma) or neuroblastoma

Most common tumor of the renal pelvis

Transitional cell carcinoma

Benign tumor of kidney often associated with tuberous sclerosis

Angiomyolipoma

Most common renal malignancy

Renal cell carcinoma

Clear cells

Renal cell carcinoma

Associated with phenacetin abuse, cigarette smoking, cyclophosphamide, and aniline dyes

Transitional cell carcinoma

Large, benign tumor of kidney, composed of eosinophilic cells; arises from the intercalated cells of collecting duct

Oncocytoma

Secondary polycythemia

Renal cell carcinoma

Associated with Schistosoma haematobium

Squamous cell carcinoma of the bladder

Invades renal vein and sometimes IVC

Renal cell carcinoma

Painless hematuria in an older patient who smokes

Transitional cell carcinoma of the bladder

Classically manifests clinically with hematuria, flank pain, and a flank mass

Renal cell carcinoma

Which gene is most commonly altered in clear cell carcinomas?

VHL (von Hippd-Lindau) gene (mutated or hypermethylated)

Which gene is most commonly altered in papillary renal cell carcinomas?

MET

Which hormone is secreted by 5% to 10% of all renal cell carcinomas?

Erythropoeitin

Renal cell carcinomas (RCC) are associated with ectopic production of which other hormones?

ACTH, renin, parathyroid hormone receptor protein (PTHrp), prolactin

Why is RCC often refractory to chemotherapy?

Expression of P-glycoprotein, a marker of multidrug resistance

Name the syndrome characterized by Wilms tumor plus each of the following findings:

Gonadal dysgenesis, nephropathy associated with WT1 gene mutations

Denys-Drash syndrome

WT1 gene mutation, aniridia, GU malformations, and mental/motor retardation

WAGR complex

Organomegaly, hemihypertrophy, macroglossia, gigantism, neonatal hypoglycemia associated with the WT2 gene

Beckwith-Wiedemann syndrome

Name the most common genetic defect associated with each of the following:

Transitional cell carcinoma

Chromosome 9p and 9q alterations

Renal cell carcinoma

Alterations of chromosome 3 affecting the VHLgene

Wilms tumor

Deletion of WTLgene (tumor suppressor gene on llplS)

Beckwith-Wiedemann syndrome

WT2 gene deletion (11p15.5)

What is the inheritance pattern of Beckwith-Wiedemann syndrome?

Genomic (paternal) imprinting

Urinary System

Name the urinary disease associated with each of the following statements:

Michaelis-Gutmann bodies

Malakoplakia

Fibrous masses over the sacrum and lower aorta that encroach on the ureters causing obstruction and hydronephrosis

Sclerosing retroperitonitis

Disease characterized by chronic bacterial cystitis with yellow and gray plaques in the mucosa of the bladder

Malakoplakia

How does chronic urinary outlet obstruction affect the bladder wall?

Chronic obstruction causes bladder wall hypertrophy

What are the common symptoms of lower urinary tract infection (cystitis)?

Dysuria, frequency, urgency

What is the most common source of bacteria that causes cystitis?

Colon (E. coli = 80%)

Why are women at 10 times the risk of men for developing a urinary tract infection (UTI)?

The female urethra is shorter and more likely to be colonized with fecal flora.

List the most common UTI organisms:

”SEEKS PP”

Serratia marcescens

Escherichia coli

Enterobacter cloacae

Klebsiella pneumoniae

Staphylococcus saprophyticus

Proteus mirabilis

Pseudomonas aeruginosa

Which UTI-causing bacterium is frequently nosocomial, drug-resistant, and may produce a red pigment?

Serratia marcescens

Isomorphic red cells in the urine suggest bleeding from what portion of the urinary tract?

Lower urinary tract (ie, nonglomerlular bleeding)

What type of trauma commonly causes extravasation of urine into the superficial perineal space?

Straddle injury (rupture of urethra below urogenital diaphragm)

Name the four types of urinary incontinence:

1. Stress

2. Urge

3. Overflow

4. Total

Name the type of voiding dysfunction or incontinence associated with the following characteristics:

A small urinary bladder and detrusor overactivity resulting in bladder wall thickening

Hypertonic neurogenic bladder

A large urinary bladder and detrusor areflexia that may result in overflow incontinence

Atonic neurogenic bladder

Small amounts of urine leakage associated with coughing, laughing, or straining

Stress incontinence

Leakage of urine associated with sudden, strong need to urinate

Urge incontinence

PHARMACOLOGY—RENAL

For each of the f ollowing drugs, provide the following:

1. The mechanism and locationof action (MLOA)

2. Indication(s) (IND)

3. Significant side effects and uniquetoxicity (TOX) (if any)

Furosemide, ethacrynic acid

MLOA: inhibitor of Na+/K+/2CF cotransporter in thick ascending loop of Henle

IND: diuresis, hypertension, CHF, and other edematous states (ascites, nephrotic syndrome, etc.)

TOX: “CHIA DOG”

Calciuria

Hypokalemic metabolic alkalosis

Interstitial nephritis

Allergy to sulfa

Dehydration

Ototoxicity

Gout

Spironolactone

MLOA: competitive aldosterone receptor antagonist; acts in collecting duct (CD)

IND: diuresis, CHF

TOX: hyperkalemic metabolic acidosis, gynecomastia, antiandrogen effects

Triamterene and amiloride

MLOA: block Na+/K+ channels in collecting duct

IND: used in combination with other diuretics (especially loop and thiazide diuretics) for their K+-sparing properties

TOX: leg cramps (triamterene)

Acetazolamide

MLOA: carbonic anhydrase inhibitor (CAI) →↓ HCO_3- reabsorption in PCT →↑ urine osmolarity

IND: diuresis, glaucoma

TOX: metabolic acidosis, ammonia toxicity, neuropathy. Note: sulfa allergy

Mannitol

MLOA: ↑ tubular fluid osmolarity →↑ urine flow; acts in PCT, thin descending limb, and CD

IND: diuresis, elevated intracranial pressure (ICP)

TOX: pulmonary edema, dehydration

Thiazides—chlorothiazide, hydrochlorothiazide

MLOA: inhibitor of NaCl reabsorption in early DCT →↑ urine osmolarity

LOA: DCT

IND: hypertension, CHF

TOX: may cause hyperglycemia, hyperlipidemia, hypercalcemia, and allergic response in patients sensitive to sulfa drugs

ACE inhibitors—captopril, lisinopril, enalapril

MLOA: inhibitor of ACE →↓ levels of AT II (→↑); prevents inactivation of bradykinin (potent vasodilator)

IND: hypertension, renal protective effects in diabetics, CHF

TOX: ”CAPTOPRIL”

Cough

Angioedema

Proteinuria

Taste changes

HypOtension

Pregnancy issues (fetal renal toxicity)

Rash

Increased renin and K+

Lowers AT II

Contraindicated in bilateral RAS

Losartan

MLOA: AT II receptor antagonist

IND: hypertension

TOX: dizziness, headache; teratogenic

Demeclocycline

MLOA: ADH antagonist in CD

IND: SIADH

Name the diuretic of choice in the following situations:

Diuresis in sulfa-allergic patient

Ethacrynic acid

Hypercalcemia

Loop diuretics (eg, furosemide)

Hyperaldosteronism

Spironolactone

Nephrogenic DI

Thiazide diuretics (eg, chlorothiazide)

Severe edematous states

Loop diuretics (eg, furosemide)

Elevated ICP

Mannitol

Altitude sickness

Acetazolamide

Calcium stones

Thiazide diuretics (eg, chlorothiazide)

Used in shock to maintain RBF

Mannitol

Which diuretics decrease blood pH?

CAIs and K+-sparing diuretics

Which diuretics increase blood pH?

Loop and thiazide diuretics

Which diuretics increase urinary Ca^2+?

Loop diuretics and spironolactone

Which diuretics decrease urinary Ca^2?

Thiazide diuretics and amiloride

Which diuretics increase urinary NaCl?

All classes

CHAPTER 10

Hematology and Oncology

EMBRYOLOGY

From what embryonic layer are angioblasts derived?

Mesoderm

Name the site(s) of red blood cell (RBC) production during each of the following developmental phases:

First trimester

Yolk sac

Second trimester

Liver and spleen

Third trimester

Central and peripheral skeleton

Postpartum

Axial skeleton

PATHOLOGY

Coagulopathy

What is the most common inherited hypercoagulable state?

Factor V Leiden

The factor V Leiden mutation inhibits factor V cleavage by which protein?

Protein C

What is the effect of estrogen, endogenous or exogenous, on thrombosis?

Estrogen induces a hypercoagulable state.

What clotting factors require vitamin K for their synthesis?

Factors II, VII, IX, X, and proteins C and S

What common laboratory test is used to assess the intrinsic coagulation system?

Partial thromboplastin time (PTT)

What common laboratory test is used to assess the extrinsic coagulation pathway?

Prothrombin time (PT)

What commonly used anticoagulant interferes with the extrinsic pathway?

Warfarin. Remember: “WEPT“—Warfarin affects the Extrinsic pathway and is monitored by PT.

The use of the chelator, ethylene diamine tetra acetate (EDTA), as an anticoagulant, in tubes is designed to inactivate what factor in the blood?

Calcium

What inhibitor of the coagulation cascade inactivates factors Va and VIIIa?

Protein C

What are the two major functions of von Willebrand factor?

1. Transport of factor VIII

2. Linkage of platelets and collagen

Dysfunction of what clotting component results in mucous membrane hemorrhage, petechiae, purpura, and prolonged bleeding time?

Platelet abnormalities

Dysfunction of what clotting component results in hemarthroses, purpura, and prolonged PT and/or PTT?

Coagulation factor abnormalities

Name the coagulopathy associated with the following clinical and pathologic features:

Most common hereditary bleeding disorder

von Willebrand disease

Most common type of hemophilia

Hemophilia A (factor VIII deficiency)

Most common cause of acquired platelet dysfunction

Aspirin use

Autosomal dominant (AD) disorder causing increased bleeding time

von Willebrand disease

Autosomal recessive (AR) defect in platelet adhesion caused by lack of GpIIb/IX

Bernard-Soulier disease

AR defect in platelet aggregation caused by deficiency of GpIIb/GpIIIa, a membrane receptor responsible for binding fibrinogen

Glanzmann thrombasthenia

Common presentation includes hemarthroses and easy bruising, ↑ PTT, normal PT

Hemophilia (A and B)

Prolonged bleeding time with normal platelet count, normal PT, and ↑ PTT

von Willebrand disease

Prolonged PT, PTT, ↑ bleeding time, thrombocytopenia, presence of fibrin split products

Disseminated intravascular coagulation (DIC)

Normal PT, PTT, normal platelet count, ↑ bleeding time

Aspirin use

Syndrome characterized by antiplatelet antibodies (commonly anti-Ib-IX or IIb-IIIa), often post-viral infections

Idiopathic thrombocytopenia (ITP)

Syndrome characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, and neurologic symptoms

Thrombotic thrombocytopenic purpura (TTP)

Widespread hyaline microthrombi in arterioles and capillaries causing schistocytes and helmet cells

Microangiopathic hemolytic anemia

Splenomegaly, epistaxis, petechiae, generalized tender lymphadenopathy, serum antibodies (+)

SLE-autoimmune thrombocytopenia

Anemias

List five of the most common causes of microcytic anemia:

1. Iron deficiency

2. Lead poisoning

3. Chronic disease (sometimes normocytic)

4. Sideroblastic

5. Thalassemia

List four of the most common causes of normocytic anemia:

1. Sickle cell anemia

2. Aplastic anemia

3. Acute blood loss

4. Hemolytic anemia

List five of the most common causes of macrocytic anemia:

1. Liver disease

2. Vitamin B_12 deficiency

2. Folate deficiency

4. Alcoholism

5. Hypothyroidism

What is the primary site of iron absorption? Vitamin B_12? Folate?

Duodenum; terminal ileum (need intrinsic factor); jejunum (respectively)

What is the major cause of iron deficiency anemia in adults?

Menorrhagia or gastrointestinal (GI) bleeding (ie, colon cancer, ulcers)

What are two common clinical complaints in an anemic patient?

1. Dyspnea on exertion

2. Fatigue

Which amino acid substitution in the β-globin gene is most commonly seen in sickle cell anemia?

Glu6 → Val

What is the major type of hemoglobin in homozygous sickle cell anemia?

HbS

In sickle cell disease, what is the mechanism of ischemic necrosis of the bones, lungs, liver, brain, spleen, or penis?

↓ O_2 tension → abnormal RBCs sickle → microvascular occlusions

What is the major regulatory enzyme in heme biosynthesis?

Aminolevulinate (ALA) synthase

What two common enzyme deficiencies can cause hemolytic anemia?

1. Glucose-6-phosphate dehydrogenase (G6PD)

2. Pyruvate kinase

What hemolytic anemia is associated with exposure to oxidant stress?

G6PD deficiency

What two common RBC membrane defects can cause hemolytic anemia?

1. Hereditary spherocytosis

2. Paroxysmal nocturnal hematuria (PNH)

What common cause of atypical pneumonia is associated with cold autoimmune hemolytic anemia?

Mycoplasma pneumoniae

What type of anemia is caused by lack of intrinsic factor (IF) secretion by gastric parietal cells?

Pernicious anemia (vitamin B_12 deficiency)

What two autoimmune diseases of the GI tract can cause megaloblastic anemia?

1. Pernicious anemia (due to lack of IF production)

2. Crohn disease of the distal ileum (due to lack of IF-B_12 complex reabsorption)

What parasites are capable of causing megaloblastic anemia?

Diphyllobothrium latum (by depleting B_12) and Giardia lamblia (by depleting folate)

How does gastric resection cause megaloblastic anemia?

Parietal cells, which are responsible for IF production may be removed when the gastric fundus is resected.

What type of malignancy is associated with pernicious anemia?

Gastric carcinoma

Name three medications capable of causing autoimmune hemolytic anemia:

1. Penicillin

2. Cephalosporins

3. Quinidine

What types of malignancies are associated with autoimmune hemolytic anemia?

Leukemias and lymphomas

What laboratory tests are seen in hemolytic anemia?

↑ Unconjugated bilirubin, ↑ urine urobilinogen, ↓ hemoglobin, hemoglobinuria, ↓ haptoglobin, hemosiderosis

Name two commonly used medications that can cause aplastic anemia:

1. Nonsteroidal anti-inflammatory drugs (NSAIDs)

2. Chloramphenicol

What happens to the total iron binding capacity (TIBC), serum iron concentration, and percent saturation of transferrin in each of the following diseases?

Iron deficiency anemia

↑ TIBC, ↓ serum iron, ↓ % saturation

Anemia of chronic disease

↓ TIBC, ↓ serum iron, normal saturation

Iron overload

Normal TIBC, ↑ serum iron, maximal saturation

Name the type(s) of anemia associated with the following clinical and pathologic features:

Most common type of anemia

Iron deficiency anemia

Abnormal Schilling test

Pernicious anemia

ABO incompatibility, lymphoid neoplasm, Raynaud phenomena, anti-i antibodies

Cold autoimmune hemolytic anemia

Atrophic glossitis

Pernicious anemia

Autosplenectomy

Sickle cell anemia

Basophlilic stipling of erythrocytes, blue/gray discoloration at gumline, wrist/foot drop

Anemia from lead poisoning

Celiac sprue

Folate deficiency anemia (megaloblastic)

Chronic atrophic gastritis

Pernicious anemia

Colon cancer

Iron deficiency anemia (early) and anemia of chronic disease (late)

Crescent-shaped erythrocytes and Howell-Jolly bodies

Sickle cell anemia

Deficiency of α- or β-globin gene synthesis

Thalassemia

Deficiency of decay accelerating factor

Paroxysmal nocturnal hemoglobinuria

Demyelination of the dorsal and lateral tracts of the spinal cord

Pernicious anemia

End-stage liver disease

Macrocytic anemia

Helmet cells, burr cells, triangular cells

Microangiopathic anemia (2° to DIC, thrombotic thrombocytopenic purpurahemolytic-uremic syndrome [TTPHUS], or mechanical heart valves)

Hypersegmented polymorphonuclears (PMNs)

Vitamin B_12 or folate deficiency anemia

Increased serum lactate dehydrogenase (LDH)

Hemolytic anemia

Microcytosis, atrophic glossitis, esophageal webs (Plummer-Vinson syndrome)

Iron deficiency anemia

Pancytopenia and fatty infiltration of bone marrow

Aplastic anemia

Systemic lupus erythematosus (SLE), chronic lymphocytic leukemia (CLL), lymphomas, drugs; + direct Coombs test (due to IgG autoantibodies)

Warm autoimmune hemolytic anemia

AD deficiency of spectrin, positive osmotic fragility test

Hereditary spherocytosis

Reduced erythropoietin

Anemia of chronic disease

Ringed sideroblasts

Sideroblastic anemia

Susceptibility to infection by encapsulated organisms

Sickle cell anemia (from splenic autoinfarction)

Transient normocytic anemia

Anemia of acute blood loss

What is the genetic defect in thalassemias?

Splicing defect, causing decreased α or β sub-chain production

Name the type of thalassemia responsible for each of the following findings:

β-Thalassemia associated with growth retardation, frontal bossing, and hepatosplenomegaly (HSM) (from extramedullary hematopoesis), jaundice, and iron overload (2° to transfusions), and ↑ Hgb F

β-Thalassemia major (β–/β–); Note: β-thalassemia minor (β+/β-), typically asymptomatic

α-Thalassemia associated with mild microcytic anemia, usually asymptomatic

α-Thalassemia minor (two alleles affected); Note: when only one allele involved (carrier state) → no anemia

α-Thalassemia associated with pallor, splenomegaly, chronic hemolytic anemia, and intraerythrocytic inclusions

Hgb H disease (three alleles affected)

α-Thalassemia associated with stillborn fetus

Hydrops fetalis (all four alleles affected)

White Blood Cell (WBC) Neoplasms

What are the two major categories of lymphoma?

1. Hodgkin disease (HD)

2. Non-Hodgkin lymphoma (NHL)

Name the general type of lymphoma (HD or NHL) associated with the following clinical and pathologic features:

Interleukin (IL)-5 secreting Reed Sternberg (RS) cells

HD

Commonly arises from B cells NHL

NHL

Constitutional symptoms including Both fever, night sweats, weight loss

Both

Mediastinal lymphadenopathy, contiguous spread

HD

Many cases associated with Epstein-Barr virus (EBV)

HD

Peripheral lymphadenopathy, noncontiguous spread

NHL

Bimodal age distribution, but most common in young men

HD

Peak incidence from 20 to 40 years of age

NHL

Associated with immunosuppression including AIDS

NHL

Painful lymphadenopathy with alcohol consumption

HD

Name the type of HD associated with each of the following clinical and pathologic findings:

Most common type

Nodular sclerosis

Abundance of RS cells

Mixed cellularity

Lacunar cells and collagen banding

Nodular sclerosis

Commonly seen in older patients with HD

Mixed cellularity

Widely disseminated disease with poor prognosis

Lymphocyte depletion

More common in females

Nodular sclerosis

Abundance of lymphocytes

Lymphocyte predominance

Commonly seen in men 35 years presenting with cervical or axillary lymphadenopathy

Lymphocyte predominance

High proportion of RS cells relative to lymphocytes

Lymphocyte depletion

Name the type of NHL associated with each of the following clinical and pathologic findings:

Overexpression of cyclin D1

Mantle cell lymphoma

Starry-sky appearance on histopathology

Burkitt lymphoma

Clinically similar to CLL; characterized by nodules of small lymphocytes

Small cell lymphocytic lymphoma

Older adults with BCL2 gene mutations

Follicular lymphoma

Often appears at extranodal sites and can cause small bowel obstruction

Diffuse large cell lymphoma

Child presenting with enlarging mandibular mass

Burkitt lymphoma

Common in children who present with a mediastinal mass and a syndrome similar to that of acute lymphocytic leukemia (ALL)

Lymphoblastic lymphoma

TdT+ lymphocytes

Precursor B- or T-cell acute lymphoblastic leukemia/lymphoma

Endemic in Africa and associated with EBV

Burkitt lymphoma

Name the specific leukemia associated with the following age brackets:

0 to 14 years old

ALL

15 to 39 years old

AML

40 to 59 years old

AML and CML

> 60 years old

CLL

Name the specific leukemia associated with each of the following findings:

Very high white cell counts, often >200,000

Chronic myelogenous leukemia (CML)

Isolated lymphocytosis

CLL

TdT+ lymphoblasts

ALL

Large, immature myeloblasts predominate

Acute myelogenous leukemia (AML)

Neoplastic pre-T or pre-B lymphocytes, CD10 ©

ALL

CD19/CD20 and CD5 © malignant cells

CLL

Bone marrow is replaced with myeloblasts

AML

Philadelphia chromosome t(9:22)

CML

Auer rods

AML (M3 > M2 > M1)

Low leukocytic alkaline phosphatase

CML (also seen in paroxysmal nocturnal hematuria)

Associated with fatigue, thrombocytopenia, signs of anemia, frequent infections, leukemia cutis, and DIC

AML (M3)

Bone pain, fever, generalized lymphadenopathy, HSM, and signs of central nervous system (CNS) spread

ALL

Excellent prognosis if treated early

ALL

May progress to AML

CML

Most responsive to therapy

ALL

Associated with prior exposure to radiation

CML

Peripheral leukocytes containing tartarate-resistant acid phosphatase (TRAP) and cytoplasmic projections

Hairy cell leukemia (Remember: “TRAP the Hairy beast”)

Myeloproliferative Disorders

Name the four chronic myeloproliferative disorders:

1. CML

2. Polycythemia vera

3. Essential thrombocytosis

4. Myelofibrosis with myeloid metaplasia

Name the myeloproliferative disorder associated with each of the following clinical and pathologic findings:

↑ RBC mass and low/normal erythropoietin

Polycythemia vera

Tear drop deformity of erythrocytes, bone marrow hypercellularity

Myelofibrosis with myeloid metaplasia

Plethoric complexion, pruritus after showering, blurred vision, splenomegaly, and epistaxis

Polycythemia vera

Erythromelalgia (throbbing or burning of hands and feet)

Essential thrombocytosis

Basophilia

Polycythemia vera

Widespread extramedullary hematopoesis with megakaryocytic proliferation in the bone marrow

Myelofibrosis with myeloid metaplasia

Hyperviscosity syndrome

Polycythemia vera and essential thrombocytosis

Peripheral thrombocytosis, bone marrow megakaryocytosis, and splenomegaly

Essential thrombocytosis

Name the plasma cell disorder associated with the following clinical and pathologic findings:

Bone pain, osteopenia, pathologic fractures, and “punched-out” lytic lesions on x-ray

Multiple myeloma

Russel bodies and “plymphocytes” (plasmacytoid lymphocytes)

Waldenstrom macroglobulinemia

Bence-Jones proteinuria

Multiple myeloma and Waldenstrom macroglobulinemia

Small M-spike on plasma electrophoresis in an otherwise healthy patient

Monoclonal gammopathy of undetermined significance (MGUS)

Hypercalcemia; renal insufficiency

Multiple myeloma

Hyperviscosity syndrome

Waldenstrom macroglobulinemia

Large M-spike on plasma electrophoresis

Multiple myeloma and Waldenstrom macroglobulinemia

Primary amyloidosis

Multiple myeloma

Peripheral Blood Smear

Name the condition associated with each of the following peripheral blood smear findings:

Defective PMN degranulation → accumulation of giant granules in PMNs and other leukocytes

Chediak-Higashi anomaly

Atypical lymphocytes

Infectious mononucleosis

Large numbers of Auer rods (Faggot cells)

AML (M3 subtype)

Basophilic stippling

Lead poisoning

Burr cells (echinocytes)

Burns, uremia

Dumbbell-shaped bilobed nuclei

Pelger-Huet anomaly

Giant platelets

Bernard-Soulier disease, May-Hegglin anomaly

Heinz bodies, bite cells

G6PD deficiency

Helmet cells, schistocytes

Microangiopathic hemolytic anemia (DIC, TTP, HUS)

Howell-Jolly bodies

Asplenia

Hypersegmented PMN nuclei

Megaloblastic anemia

Intracytoplasmic rings

Malaria, babesiosis

Lymphocytic cerebriform nuclei

Sézary syndrome

Nucleated erythrocytes

Hemolytic anemia

Rouleau formation

Multiple myeloma and Waldenstrom macroglobulinemia

Small platelets

Wiskott-Aldrich syndrome

Smudge cells

CLL

Spherocytes

Hereditary spherocytosis

Spur cells (acanthocytes)

Abetalipoproteinemia, liver disease

Target cells (codocytes)

Thalassemias, iron deficiency anemia, liver disease, sickle cell anemia

Teardrop cells (dacryocytes)

Myelofibrosis

Toxic granulations in leukocytes (Dohle bodies)

Sepsis

Chromosomal Translocations

Name the neoplasm associated with the following chromosomal translocations and genes/gene products:

t(11:14) protooncogene under Ig promoter

Mantle cell lymphoma

t(11:22) EWS (EWS-FLI1 fusion protein)

Ewing sarcoma

t(14:18) BCL2

Follicular lymphoma

t(15:17) (PML/RAR-β [retinoic acid receptor alpha])

AML (M3 subtype, treated with retinoic acid)

t(3:6) VHL

von Hippel-Lindau syndrome (t[3:8] and t[3:11] are two common variants seen in VHL)

t(8:14) c-myc and IgH

Burkitt lymphoma (t[8:22] and t[2:8] are two common variants seen in Burkitt lymphoma)

t(9:22) bcr-abl fusion protein

CML (treated with imatinib)

Tumor Markers

Name the neoplasm associated with the following tumor markers:

α_1-AT

Liver cancer, yolk-sac tumors

α-Fetoprotein (AFP)

Germ cell tumors, hepatocellular carcinoma

Alkaline phosphatase

Metastatic bone involvement, Paget disease

β-HCG

Hydatiform moles, Choriocarcinoma, Gestational trophoblastic tumors

CA-125

Ovarian cancers

Carcinoembryonic antigen (CEA)

Colon, pancreatic, and other cancers of the GI tract

Prostate-specific antigen (PSA)

Prostate cancer

S-100

Melanoma, neural tumors

Cancer Genetics

For each of the following tumor suppressor genes, state the function and the malignancy/malignancies they are associated with:

APC

Function: regulation of β-catenin in the Wnt/β-catenin signaling pathway—promotes cell adhesion and regulates cell proliferation

Associated malignancies: familial adenomatosis polyposis (FAP) and many GI cancers

BRCA1 and BRCA2

Function: DNA repair and transcriptional regulation

Associated malignancies: breast and ovarian cancers

NF1 and NF2

Function: regulates signal transduction through the ras pathway

Associated malignancies: neurofibromas, schwannomas; (NF-2 also associated with meningioma)

p16

Function: regulates cell cycle by inhibiting cyclin-dependent kinases

Associated malignancies: pancreatic and esophageal carcinomas and malignant melanoma

p53

Function: regulates cell death and proliferation in response to DNA damage

Associated malignancies: most human cancers

Rb

Function: regulates transition from G1 to S in the cell cycle by sequestering E2Fs, a family of transcription factors

Associated malignancies: retinoblastoma, osteosarcoma

WT1

Function: inhibits transcription of genes promoting cell proliferation

Associated malignancies: Wilms tumor

For each of the following oncogenes, state the function and the malignancy/malignancies they are associated with:

abl

Function: promotes cell proliferation through tyrosine kinase activity

Associated malignancies: CML, ALL

BCL2

Function: overexpression prolongs cell survival by inhibiting apoptosis

Associated malignancies: follicular and undifferentiated lymphomas

cyclin D

Function: promotes cell proliferation by stimulating the phosphorylation of pRb

Associated malignancies: lymphoma, breast, liver, and esophageal cancers cyclin D

CDK4

Function: promotes cell proliferation by phosphorylating pRb

Associated malignancies: sarcoma, glioblastoma multiforme, malignant melanoma

HER2/neu

Function: amplification promotes cell proliferation by enhancing growth factor signal transduction

Associated malignancies: breast, ovarian, lung, stomach cancers

myc

Function: promotes cell proliferation by transcriptional activation of specific genes

Associated malignancies: Burkitt lymphoma, small cell carcinoma of the lung, neuroblastoma

ras

Function: signal transduction through the MAP kinase pathway

Associated malignancies: colon cancer and many other human cancers

ret

Function: receptor tyrosine kinase that promotes cell proliferation in response to growth factors

Associated malignancies: multiple endocrine neoplasia 2A and 2B; familial medullary thyroid carcinoma

sis

Function: β-chain of PDGF which promotes cell proliferation

Associated malignancies: astrocytomas, osteosarcomas

Miscellaneous Oncology

Name the type of neoplasm associated with the following diseases:

Actinic keratosis

Squamous cell carcinomas of skin

AIDS

Aggressive malignant lymphomas, Kaposi sarcoma, brain lymphomas

Barrett esophagitis

Esophageal adenocarcinoma

Chronic atrophic gastritis

Gastric adenocarcinoma

Cirrhosis

Hepatocellular carcinoma

Down syndrome

ALL

Dysplastic nevus

Malignant melanoma

Immunodeficiency states

NHL

Myasthenia gravis

Thymoma

Paget disease of bone

Secondary osteosarcoma and fibrosarcoma

Plummer-Vinson syndrome Tuberous sclerosis

Squamous cell carcinomas of esophagus

Ulcerative colitis

Colonic adenocarcinoma

Xeroderma pigmentosa

Squamous and basal cell carcinomas of skin

List the four major differences between benign and malignant neoplasms:

1. Differentiation and anaplasia

2. Rate of growth

3. Local invasion

4. Metastases (most important difference)

What are the three ways a tumor can spread?

1. Invasion of lymphatic system (eg, carcinoma of the breast)

2. Hematogenous (typical of sarcomas)

3. Seeding of body cavity (eg, ovarian cancer)

What four classes of genes are the primary targets for genetic mutation leading to cancer?

1. Protooncogenes (promote cellular growth)

2. Tumor suppressor genes (inhibit cellular growth)

3. Genes that regulate and mediate apoptosis

4. Genes that regulate and mediate DNA repair

What three genetic mechanisms can lead to the activation of protooncogenes?

1. Point mutations

2. Chromosomal rearrangements

3. Amplification

What three chromosomal abnormalities are characteristic of tumor cells?

1. Amplification

2. Deletion

3. Translocation

What three factors influence tumor growth?

1. Doubling time of tumor cells

2. Cell proliferation

3. Cell death (apoptosis)

Name the six small, round, blue cell tumors of childhood:

1. Ewing sarcoma

2. Lymphoma

3. Neuroblastoma

4. Medulloblastoma

5. Rhabdomyosarcoma

6. Primitive neuroectodermal tumors

Chemical Carcinogens

What are the two steps in the process of chemical carcinogenesis?

1. Initiation: cells undergo irreversible genetic mutation.

2. Promotion: chemicals promote growth of initiated cells.

Name the neoplasm associated with each of the following chemical, viral, and microbial carcinogens and types of radiant energy:

Aflatoxin

Hepatocellular carcinoma

Aniline dyes

Bladder cancer

Aromatic hydrocarbons

Lung cancer (aromatic hydrocarbons found in cigarettes)

Asbestos

Malignant mesothelioma

EBV

Burkitt lymphoma, nasopharyngeal cancer, B-cell lymphoma in AIDS patients, some types of HD

Estrogen

Breast carcinoma and endometrial carcinoma

Helicobacter pylori

Gastric adenocarcinoma and marginal zone lymphoma (MALToma)

Hepatitis B virus

Hepatocellular carcinoma

Human papilloma virus

Cervical squamous cell carcinoma and genital warts

Human T-cell lymphocytic virus-1 (HTLV-1)

T-cell leukemia/lymphoma

Ionizing radiation Nitrosamines

Myeloid leukemias and thyroid cancers

Polyvinylchloride (PVC) assembly

Hepatic hemangiosarcoma

Ultraviolet radiation

Skin cancers

Schistosoma haematobium

Squamous cell carcinoma of the urinary bladder

Paraneoplastic Syndromes

Name the process of profound weight loss and weakness due to muscle and fat loss in a patient with an advanced neoplasm:

Cancer cachexia

Name the tumor associated with the following paraneoplastic syndromes:

Acanthosis nigracans

Many types of visceral malignancies

Carcinoid syndrome

Carcinoid and neuroendocrine carcinomas of the bronchi or GI tract

Clubbing of fingers

Pulmonary or thoracic malignancies

Cushing syndrome

Adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma or a cortisol-secreting adrenal adenoma

DIC

AML (M3)

Hypercalcemia

Parathyroid hormone (PTH)-secreting squamous cell carcinoma of the lung

Lambert-Eaton myasthenic syndrome

Small cell carcinoma of the lung

Thrombophlebitis

Pancreatic or lung adenocarcinoma

Syndrome of inappropriate antidiuretic hormone (SIADH)

Antidiuretic hormone (ADH)-secreting small cell carcinoma of the lung

PHARMACOLOGY

Medication for Anemia

Name the drug of choice for each of the following groups of anemic patients:

Adolescent girls with heavy periods and pregnant women

Iron

Patients on methotrexate who develop megaloblastic anemia

Folate

Elderly patients with atrophic gastritis who develop megaloblastic anemia

Cyanocobalamin (vitamin B_12)

Patients with anemia secondary to end-stage renal disease

Erythropoietin

Patients with extremely low WBC count and prone to infection

G-CSF, GM-CSF

Chemotherapeutic Agents

For each of the following drugs, provide:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects and unique toxicity (TOX) (if any)

Methotrexate

MOA: folate analog that inhibits dihydrofolate reductase and, consequently, S phase of the cell cycle

IND: leukemia, lymphoma, carcinoma, sarcoma

TOX: myelosuppression (reversible with leucovorin)

5-Fluorouracil

MOA: inhibits pyrimidine synthesis which inhibits S phase progression

IND: colon cancer and other solid tumors

TOX: myelosuppression and phototoxicity

Cytarabine

MOA: inhibits pyrimidine synthesis which inhibits S phase progression

IND: acute leukemias

TOX: neurotoxicity

6-Mercaptopurine or 6-thioguanine

MOA: inhibits purine synthesis which inhibits S phase progression

IND: leukemia, lymphoma

TOX: myelosuppression, hepatotoxicity

Busulfan

MOA: DNA alkylating agent

IND: palliative role in CML treatment

TOX: pulmonary fibrosis, hyperpigmentation

Cyclophosphamide

MOA: DNA alkylating agent

IND: NHL, breast and ovarian carcinomas

TOX: hemorrhagic cystitis (prevented with mesna), myelosuppression

Nitrosureas (carmustine, lomustine, streptozocin)

MOA: DNA alkylating agent capable of crossing the blood-brain barrier

IND: brain tumors

TOX: CNS toxicity including dizziness and ataxia

Cisplatin

MOA: DNA alkylating agent

IND: testicular cancer, female reproductive tract cancers, bladder and testicular cancers

TOX: nephrotoxicity and acoustic nerve damage

Doxorubicin/adriamycin

MOA: intercalates into DNA and inhibits DNA replication

IND: Hodgkin disease, myeloma, sarcoma, solid tumors

TOX: cardiotoxicity, alopecia, myelosuppression

Bleomycin

MOA: intercalates into DNA and causes DNA strand breaks

IND: testicular cancer, lymphomas

TOX: pulmonary fibrosis, myelosuppression

Etoposide

MOA: inhibits topoisomerase, causing double-stranded breaks in DNA

IND: small cell carcinoma of lung, prostate cancer, testicular cancer

TOX: Bone marrow suppression, hypotension

Prednisone

MOA: may trigger apoptosis

IND: CLL, HD, lymphomas

TOX: cushingoid reaction, immunosuppression, cataracts, acne, osteoporosis, hypertension (HTN), peptic ulcers, hyperglycemia

Tamoxifen/raloxifene

MOA: estrogen receptor agonist/antagonist

IND: breast cancer

TOX: increased risk of endometrial cancer

Vinblastine/vincristine

MOA: binds tubulin to inhibit formation of the mitotic spindle

IND: HD, lymphoma, Wilms tumor, choriocarcinoma

TOX: vincristine: peripheral neuropathy and paralytic ileus; vinblastine: myelosuppression

Paclitaxel

MOA: binds tubulin to inhibit formation of the mitotic spindle

IND: ovarian and breast cancers

TOX: myelosuppression, hypersensitivity

Anticoagulants

What test is used to monitor anticoagulation in a patient treated with heparin?

PTT

What test is used to monitor anticoagulation in a patient treated with warfarin?

PT

Warfarin

MOA: causes synthesis of dysfunctional vitamin K-dependent clotting factors (II, VII, IX, X)

IND: chronic treatment and prophylaxis of DVT

TOX: hemorrhage, teratogenic, osteoporosis

Heparin

MOA: increases PTT by activating antithrombin III

IND: acute treatment of DVT, pulmonary embolus, angina, myocardial infarction (MI), ischemic stroke

TOX: hemorrhage, Heparin-Induced Thrombocytopenia Syndrome (HITS)

Low-molecular-weight heparin (LMWH) (eg, enoxaparin)

MOA: similar to heparin

IND: anticoagulation outside of the hospital, commonly for DVT

Thrombolytics (streptokinase, urokinase, tissue plasminogen activator, anistreplase)

MOA: facilitate the conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots

IND: acute therapy for MI and ischemic stroke

TOX: hemorrhage

Clopidogrel and ticlopidine

MOA: antiplatelet agent that blocks adenosine diphosphate (ADP) receptors to inhibit platelet aggregation

IND: acute coronary syndrome, interventional cardiology procedures, transient ischemic attacks, and stroke

TOX: hemorrhage, leukopenia, diarrhea

Eptifibatide and tirofiban

MOA: prevent platelet aggregation by blocking glycoprotein IIb/IIIa receptors

IND: acute coronary syndromes

TOX: hemorrhage

CHAPTER 11

Skin and Connective Tissues

EMBRYOLOGY/ANATOMY/HISTOLOGY

Name the embryonic structures that give rise to each of the following:

Epidermis

Ectoderm

Melanocytes

Neural crest cells

Name the layers of the epidermis:

“Californians Like Girls in String Bikinis” (from surface → base)

Stratum Corneum

Stratum Lucidum (lacking in thin skin of face and genitalia)

Stratum Granulosum

Stratum Spinosum

Stratum Basalis

What epidermal dendritic cells are responsible for antigen presentation?

Langerhans cells

Name the type of collagen described by the following statements:

Found in Bone, tendons, skin, fascia, cornea, and dentin; replaces reticulin later in wound repair

Type I (Remember: bONE)

Found in Cartilage, nucleus pulposus, and ocular vitreous body

Type II (Remember: carTWOlage)

Found in skin, blood vessels, uterus, fetal tissues, and involved in early wound repair (granulation tissue)

Type III (Reticulin)

Component of Basement membrane or basal lamina

Type IV (Remember: type IV, under the floor/basement membrane)

Found at epiphyseal plates

Type X

Accounts for ~90% of collagen in the body

Type I

Mnemonic for collagen types I to IV

“Be Cool, Read Books”

Name the epithelial cell specialization described by the following statements:

Allows adjacent cells to communicate via connexons

Gap junction. Note: missing in cancer cells

Connects cells to underlying extracellular matrix

Hemidesmosomes

Extends around entire perimeter; contains E-cadherin and actin filaments

Zona adherens

Prevents diffusion across intracellular space; extends around entire perimeter

Zona occludens (tight junction)

Small, discrete sites of attachment; contains desmoplakin and keratin

Macula adherens (desmosome)

Helical array of polymerized dimmers of α and β tubulin

Microtubules

How are the internal structures of cilia organized?

9 + 2 arrangement of microtubules (9 doublets around 2 central microtubules)

Which enzyme causes bending of cilia and how does it work?

Dynein is an adenosine triphosphatase (ATPase) that links the 9 doublets and causes bending by differential sliding.

Name the cytoskeletal elements that perform the following functions:

Microvilli, muscular contraction, cytokinesis, adhering junction

Actin and myosin

Cilia, flagella, mitotic spindle, neurons, centrioles

Microtubules

Vimentin, desmin, cytokeratin, glial fibrillary acid protein, neurofilaments

Intermediate filaments

Where are apocrine sweat glands found?

Axilla, mons pubis, and anal regions

PATHOLOGY

Give the dermatologic term for each of the following descriptions:

Flat, nonpalpable, circumscribed lesion 1 cm in diameter; different color than surrounding skin

Macule

A macule > 1 cm in diameter

Patch

Palpable, solid, elevated skin lesion Papule ≤5 mm in diameter

Papule

A papule > 5 mm in diameter

Plaque

Fluid-containing blister 0.5 cm in diameter

Vesicle

Fluid-containing blister > 0.5 cm in diameter

Bulla

Pus-filled, raised area

Pustule

Solid, round lesion; diameter = thickness, > 5 mm in diameter

Nodule

Name the dermatologic disorder characterized by the following descriptions:

Autosomal recessive (AR) defect in melanin synthesis → predisposition to multiple skin disorders

Albinism (oculocutaneous)

Acquired loss of epidermal melanocytes → depigmented white patches

Vitiligo

Masklike facial hyperpigmentation associated with pregnancy

Melasma

Tan-brown, evenly pigmented, localized overgrowth of melanin-forming cells of the skin present at birth with benign behavior and variable histology

Nevocellular nevus (mole)

Often multiple, atypical, irregularly pigmented lesions and on non-sun-exposed skin, that have the potential to transform into malignant melanoma

Dysplastic nevus

Eruption of comedones and pustules; ↑ during puberty and adolescence; associated with proliferation of Propionibacterium

Acne vulgaris

Umbilicated, pearly, dome-shaped papules typically occurring in the genitals; caused by poxvirus infection

Molluscum contagiosum

Benign papilloma caused by HPV infection, most commonly found on dorsum of hand; koilocytes are characteristic

Verruca vulgaris (common wart)

Common benign neoplasm of older adults; sharply demarcated, tan-brown plaques with a “pasted on” appearance

Seborrheic keratosis (senile keratosis)

Benign, flesh-colored, dome-shaped, > 1 cm nodule with central keratin-filled plug-craterlike that resembles squamous cell carcinoma; may resolve without treatment

Keratoacanthoma

Yellowish papules or nodules that tend to occur on the eyelids; associated with hypercholesterolemia

Xanthoma (on the eyelids = xanthelasma)

Accumulation of excessive dermal collagen that can occur following skin trauma; results in large, raised tumorlike scar

Keloid

Proliferation of Langerhans cells; electron microscopy (EM) shows Birbeck granules

Histiocytosis X

A T-cell lymphoproliferative disease arising in the skin; initially simulates eczema or other inflammatory dermatoses

Mycosis fungoides (cutaneous T-cell lymphoma)

Rough, scaling epidermal lesion, usually 1 cm, due to chronic sunlight exposure; may be a precursor for squamous cell carcinoma

Actinic keratosis

Thickened, hyperpigmented skin in the flexural areas; may be suggestive of visceral malignancy

Acanthosis nigricans

Capillary hemangioma appearing as a purple-red area on the face or neck

Port-wine stain

Name the inflammatory dermal lesion associated with each of the following findings:

Pruritic, inflammatory disorders due to infection, atopy, chemicals, UV light, or repeated trauma

Dermatitis

Characteristic “target” macule or papule; associated with infections, drugs, cancers, and autoimmune disease

Erythema multiforme

Silvery scaling plaques over the knees, Psoriasis elbows, and scalp

Psoriasis

“Saw toothing” of rete ridges

Lichen planus

Munro microabscesses in the stratum corneum

Psoriasis

Pruitic eruption commonly on flexor surfaces. Associated with asthma and allergic rhinitis

Atopic dermatitis (eczema)

Wickham stria

Lichen planus

Purple, pruritic, polygonal, papules

Lichen planus

Characteristic rete elongation and parakeratosis

Psoriasis

Fever combined with erosions and hemorrhagic crusting of mucosal surfaces

Stevens-Johnson syndrome

Type IV hypersensitivity reaction following exposure to allergens such as poison ivy or poison oak

Allergic contact dermatitis

Sometimes associated with severe destructive rheumatoid arthritis-like lesions of the fingers

Psoriasis (psoriatic arthritis)

Name the blistering dermal disease associated with each of the following descriptions:

Subepidermal bullae causing detachment of the entire thickness of the epidermis

Bullous pemphigoid

Pruritic subepidermal blisters occurring in groups; eosinophils and IgA deposits at tips of dermal papillae; seen in patients with celiac disease

Dermatitis herpetiformis

Intraepidermal/suprabasal blisters that often rupture; may be fatal

Pemphigus vulgaris

Immunofluorescence demonstrates linear deposition of complement and antibodies to hemidesmosome proteins BPAG1 and BPAG2

Bullous pemphigoid

IgA and IgG antibodies to gluten

Dermatitis herpetiformis

Antibodies (Abs) to the desmosomal protein desmoglein 3 in the macula adherens

Pemphigus vulgaris

Name the neurocutaneous syndrome characterized by each of the following features:

Port-wine stains of the face, ipsilateral glaucoma, retinal lesions, and hemangiomas of the meninges

Sturge-Weber syndrome

Hypopigmented macules (ash-leaf spots), adenoma sebaceum, seizures, and mental retardation

Tuberous sclerosis

Multiple organ hemangioblastomas, cysts, and paragangliomas throughout the body

von Hippel-Lindau disease

Café au lait spots, acoustic neuromas, and meningiomas

Neurofibromatosis

Which syndrome is characterized by mycosis fungoides, erythema, and scaling?

Sézary syndrome, cutaneous T-cell lymphoma

Connective Tissue Disorders

Name the connective tissue disorder characterized by each of the following descriptions:

Immune complex deposition in almost any organ, characteristic butterfly malar rash, wire loop lesions in kidney, Libman-Sacks endocarditis, ANA, anti-dsDNA, anti-Smith antibodies

Systemic lupus erythematous

Calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, telangiectasias; anticentromere antibodies

CREST syndrome

Autosomal dominant (AD) mutation in the fibrillin-1 gene (FBN1) on chromosome 15q

Marfan syndrome

Most common form is an AD defect in collagen type I synthesis; may be confused with child abuse

Osteogenesis imperfecta

Proximal muscle weakness, elevated serum creatine kinase, less often associated with malignancy

Polymyositis

Abnormal collagen synthesis causing bleeding tendency, hypermobile joints, and hyperextensible skin

Ehlers-Danlos syndrome

Blue sclera and brittle bones

Osteogenesis imperfecta

Proximal muscle weakness, heliotrope rash, more often associated with malignancy

Dermatomyositis

Antinuclear ribonucleoprotein (anti-nRNP) antibodies

Mixed connective tissue disease

Widespread visceral involvement; anti-Scl-70 antibodies

Diffuse scleroderma

Triad of xeropthalmia (dry eyes), xerostomia (dry mouth), arthritis; anti-Ro, anti-La antibodies

Sjögren syndrome

Skin Cancer

Name the skin malignancy associated with each of the following statements:

The most common skin malignancy

Basal cell carcinoma

Associated with excessive sunlight exposure; may arise from dysplastic nevus cells

Malignant melanoma

Actinic keratosis is a precursor lesion

Squamous cell carcinoma

Locally aggressive, ulcerating, and hemorrhagic; almost never metastases

Basal cell carcinoma

Occurs in sun-exposed areas and tends to involve the lower part of the face

Squamous cell carcinoma

Occurs in sun-exposed areas and tends to involve the upper part of the face

Basal cell carcinoma

Histopathology characterized by “keratin pearls”

Squamous cell carcinoma

Histopathology shows darkly staining cells with palisading nuclei

Basal cell carcinoma

Radial phase precedes vertical growth phase

Malignant melanoma

Associated with arsenic and radiation exposure

Squamous cell carcinoma

What are the characteristics worrisome for malignant melanoma?

ABCDE’s

Asymmetry

Border (irregular)

Color

Diameter

Evolving

What is the most important prognostic factor in malignant melanoma?

Depth of invasion

What clinical variant of malignant melanoma has the poorest prognosis?

Nodular melanoma

What clinical variant of malignant melanoma often appears on the hands and feet of dark-skinned people?

Acral-lentiginous melanoma

Miscellaneous Skin Disorders

Name the dermatologic finding(s) associated with each of the following diseases:

Gastric adenocarcinoma

Acanthosis nigricans

Addison disease

Hyperpigmentation and striae

Rheumatic fever

Erythema marginatum

Kawasaki syndrome

Erythematous palms and soles; dry, red lips; desquamation of fingertips

Insulin resistance, diabetes mellitus type 2

Acanthosis nigricans

Sézary syndrome

Mycosis fungoides (lymphoma of the skin-simulating eczema)

Severe chronic renal failure

Uremic frost

Bacterial endocarditis

Osler nodes (tender, raised lesions on pads of fingers or toes) and Janeway lesions (small, erythematous lesions on palms or soles)

Xeroderma pigmentosum

Dry skin and melanoma

Henoch-Schönlein purpura

Purpuric lesions on extensor surfaces of arms, legs, buttock

Hypothyroidism

Cool, dry skin with coarse brittle hair

Graves disease

Warm, moist skin with fine hair; pretibial myxedema

Graft-versus-host disease

Maculopapular rash

von Recklinghausen disease (NF-1)

Multiple café au lait spots

Familial hypercholesterolemia

Xanthomas

Systemic lupus erythematosus

Malar rash and photosensitivity

Pellagra

Dermatitis

Name the dermatologic finding(s) associated with each of the following infectious diseases:

Anthrax

Vesicular papules covered by black eschar

Parvovirus B19

Erythema infectiosum (slapped cheek appearance)

Lyme disease

Erythema chronicum migrans

Primary syphilis

Painless chancre

Secondary syphilis

Rash over palms and soles, condyloma latum

Rocky Mountain spotted fever

Rash over palms and soles (migrates centrally)

Congenital cytomegalovirus

Pinpoint petechial “blueberry muffin” rash

HPV (in genital region)

Condylomata acuminata

Herpes simplex virus (type 1)

Painful vesicles (at border of lips)

Leprosy

Hypopigmented, anesthetic skin patches

CHAPTER 12

Musculoskeletal

ANATOMY

Name the peripheral nerve or region of the brachial plexus injured in each of the following scenarios:

Erb-Duchenne or Waiter’s tip palsy

Upper trunk of the brachial plexus (C5, C6)

Klumpke injury due to sudden upward jerk of the arm; associated with Horner syndrome

Lower trunk of the brachial plexus (C8, T1)

Claw hand (impaired wrist flexion and adduction)

Ulnar nerve

Wrist drop

Radial nerve

Vague pain in wrist with tingling, burning sensation in hand (carpal tunnel syndrome)

Median nerve

Deltoid paralysis

Axillary nerve

Winged scapula after mastectomy (paralyzed serratus anterior)

Long thoracic nerve

Foot drop

Common peroneal nerve

Loss of ability to plantarflex

Tibial nerve

Anterior shoulder dislocation

Axillary nerve

Positive distal tingling on percussion of anterior wrist (Tinel) and tingling on forced flexion (Phalen) tests

Median nerve (at wrist)

Anterior hip dislocation resulting in loss of adduction of the thigh

Obturator nerve

Loss of ability to rise from a seated position or climb stairs due to loss of gluteus maximus function

Inferior gluteal nerve

Positive Trendenlenburg sign (when contralateral leg is raised, contralateral hip falls secondary to ipsilateral gluteus medius weakness)

Superior gluteal nerve

Posterior hip dislocation

Sciatic nerve

Name the fracture associated with the following statements:

Laceration of the deep brachial artery and/or radial nerve

Midshaft fracture of the humerus

Greatest risk of upper extremity compartment syndrome in children (Volkman contracture)

Supracondylar fracture of the humerus

Young person with fall on outstretched hand, tenderness in the anatomic snuffbox

Scaphoid fracture

Caused by closed fist striking a hard object

Boxer’s fracture or fracture of the fifth metacarpal

Elderly woman falling on an outstretched hand with the wrist extended

Colles fracture (fracture of the distal radius with dorsal displacement of hand)

Associated with foot drop due to injury of common peroneal nerve

Fracture of fibular neck

Lower extremity fracture caused by landing on foot from a large vertical drop

Calcaneal fracture (must check lumbar spine x-rays for associated fracture)

List the muscles that make up the hypothenar eminence:

Opponens digiti minimi, Abductor digiti minimi, Flexor digiti minimi (OAF)

List the muscles that make up the thenar eminence:

Opponens pollicis, Abductor pollicis brevis, Flexor pollicis brevis

What are the functions of the thenar and hypothenar muscles?

Oppose, Abduct, and Flex

What muscles ADduct at the metacarpophalangeal (MCP) joints?

Palmar interosseous muscles (PAD)

What muscles ABduct at the MCP joints?

Dorsal interosseous muscles (DAB)

What ligaments make up the borders of the anatomic snuffbox?

Extensor pollicis longus, extensor pollicis brevis, abductor pollicis longus

What artery passes through the anatomic snuffbox?

Radial artery

How can one test for radial or ulnar artery patency?

Allen test (used before arterial blood sampling from the radial artery)

What structures are damaged by lateral impact to the knee/twisting injury?

The terrible triad: anterior cruciate ligament (ACL), medial collateral ligament (MCL), and medial mensicus

What does a positive anterior drawer/Lachman sign suggest?

Torn ACL

What does abnormal passive abduction (valgus instability) of the leg suggest?

Torn MCL

What is the most common site for a clavicular fracture?

Middle one-third

What is the term for increased pressure within a fascial compartment that causes damage to muscles and neurovascular structures?

Compartment syndrome

What are the six P’s of compartment syndrome?

1. Pain out of proportion/pain with passive stretch

2. Parasthesias

3. Paralysis

4. Pallor

5. Pulselessness

6. Poikilothermia (cold)

What ligaments can be stretched or torn by inversion of the ankle?

Anterior talofibular ligament (most common, “Always Tears First”), calcaneofibular (second most common), posterior talofibular ligament (least common)

What common carpal bone fracture can lead to avascular necrosis?

Scaphoid fracture

What are the muscles of the rotator cuff?

Supraspinatus, Infraspinatus, Teres minor, Subscapularis (SITS) muscles

What term is used to describe the syndrome of pain on extension of the wrist and fingers?

Lateral epicondylitis (tennis elbow)

Name the syndrome characterized by sensory loss of the medial forearm and hand, disappearance of radial pulse on turning head away from affected side, with atrophy of thenar, hypothenar, and interosseous muscles:

Thoracic outlet syndrome (often due to cervical accessory rib)

Fracture that presents with leg in abduction, external rotation, and appearing shorter than the contralateral leg

Femoral neck fracture

Injury that presents with an internally rotated and adducted leg appearing shorter than the contralateral leg?

Posterior dislocation of the hip

PHYSIOLOGY

State the key cellular events in excitation-contraction coupling in skeletal muscle:

1. Action potentials cause depolarization of T tubules.

2. Ca^2+ release from sarcoplasmic reticulum.

3. Ca^2+ binds troponin C, causes conformational change.

4. Tropomyosin moves to expose actin-binding site.

5. Actin and myosin interact to generate contractile force.

6. Ca2+ reuptake by sarcoplasmic reticulum.

How does Ca2+ activate contraction in smooth muscle cells?

By binding to calmodulin, activating myosin light-chain kinase (MLCK)

Name the type(s) of muscle fiber associated with each of the following cellular or histologic features:

Peripherally located nucleus

Skeletal muscle fibers

Centrally located nucleus

Smooth and cardiac muscle fibers

Distinct banding pattern

Cardiac and skeletal muscle fibers; bands are appearance of sarcomeres

Capacity to regenerate

Smooth muscle fibers

Z-lines

Cardiac and skeletal muscle fibers; Z-lines are borders that separate sarcomeres

Gap junctions

Smooth muscle fibers

Intercalated disks

Cardiac muscle fibers

Synapse with peripheral nerves

Skeletal muscle fibers

Inositol triphosphate (IP_3)-mediated calcium release

Smooth muscle fibers

Ca2+-mediated calcium release

Cardiac muscle fibers

Voltage-mediated, T-tubule-mediated calcium release

Skeletal muscle fibers

Troponin is the major calcium-binding protein

Cardiac and skeletal muscle fibers

Name the type of skeletal muscle fiber associated with each of the following features:

Slow twitch

Type 1—one slow

Fast twitch

Type 2

Abundant lipid stores

Type 1—fat

Red color

Type 1—red

White color

Type 2

Primarily uses anaerobic metabolism, few mitochondria

Type 2

Primarily uses aerobic metabolism, many mitochondria

Type 1—ox

Abundant glycogen stores

Type 2

Generation of a sustained force

Type 1

Generation of a sudden movement

Type 2

Mneumonic for type 1 fibers

Remember: “One Slow, Fat, Red Ox”

MUSCULOSKELETAL AND CONNECTIVE TISSUE PATHOLOGY

Nonneoplastic Bone Disorders

Name the bone disease associated with the following clinical and pathologic features:

AD disorder characterized by short limbs due to narrow epiphyseal plates, normal torso, enlarged head, frontal bossing, and bow legs

Achondroplasia, most common cause of dwarfism

A group of disorders characterized by abnormalities of type 1 collagen

Osteogenesis imperfecta

Inadequate proline and lysine hydroxylation of procollagen

Scurvy

Vitamin D deficiency → failure of bone mineralization

Rickets (children) or osteomalacia (adults)

Vitamin C deficiency → bone lesions, bleeding from gums. and petechial hemorrhages

Scurvy

Associated with blue sclera and multiple fractures

Osteogenesis imperfecta

↑ Parathyroid hormone (PTH) → “Brown tumor” of bone (fibrosis, giant cells, osteoclasts hemorrhagic debris, and cyst formation)

Osteitis fibrosa cystica (von Recklinghausen disease of bone)

Slow paramyxovirus infection of osteoblasts and osteoclasts that results in multiple fractures and ↑ serum alkaline phosphatase

Paget disease of bone (osteitis deformans)

Marrow fibrosis, moth-eaten bones on x-ray (XR), and metastatic calcifications

Osteitis fibrosa cystica (von Recklinghausen disease of bone), caused by hyperparathyroidism

Multiple lytic lesions of spine and skull

Multiple myeloma

Progressive decrease in bone mass most pronounced in menopausal women

Osteoporosis

Hereditary disorder of increased bone density caused by defective osteoclast function and bone overgrowth

Osteopetrosis

Lateral curvature of spine, usually with rotational component; most common in adolescent females

Scoliosis

Subperiosteal hemorrhage, failure of ephiphyseal cartilage replacement by osteoid, osteoporosis

Scurvy (vitamin C deficiency)

Delayed fontanelle closure, “Rachitic rosary” (thickening of costochondral junction), and Harrison groove

Rickets (vitamin D deficiency)

Marked cortical thinning and attenuation of bone trabeculae

Osteogenesis imperfecta

Poor calcification of bone leading to skeletal abnormalities, including bowing of legs, craniotabes, and pigeon breast deformity in children

Rickets

Mosaic pattern of lamellar bone, increased serum alkaline phosphatase

Paget disease of bone (osteitis deformans)

Bone infection → sequestrum and involucrum around the inflammatory focus

Pyogenic osteomyelitis

Infarction of osteocytes leading to joint pain and osteoarthritis

Avascular necrosis

Avascular necrosis of the head of the femur; typically presents with painless limp in obese adolescent

Legg-Calve-Perthés disease

Partial avulsion of tibial tuberosity; typically presents as knee pain in an active adolescent

Osgood-Schlatter disease

Bacterial infection of bone, causing an acute febrile illness and localized pain and inflammation at the site of infection

Pyogenic osteomyelitis

Granulomatous disease caused by spread of tuberculosis to spine

Pott disease

Vertebral compression fractures causing pain, kyphosis, and loss of height in the elderly

Osteoporosis

What is the most likely etiology of Paget diease?

Slow reaction to paramyxovirus infection of osteoblasts

What are the three phases of Paget disease of bone?

1. Osteolytic phase: bone reabsorption by large osteoclasts

2. Mixed phase: osteoblastic and osteoclastic activity results in mosaic pattern of bone

3. Burnt-out phase: osteoblastic activity predominates

Name six complications of Paget disease of bone:

1. High-output cardiac failure due to intraosseous atrioventricular (AV) shunting

2. Hearing loss

3. Leonitiasis ossea

4. Osteosarcoma

5. Osteoarthritis

6. Bone pain from fractures

Osteomyelitis

Name the most common organism(s) responsible for pyogenic osteomyelitis in each of the following patients:

Otherwise healthy adult

Staphylococcus aureus

Intravenous drug user

Pseudomonas spp.

Sickle cell anemia patient

Salmonella

Newborn

Streptococci spp. or Escherichia coli

Child

Staphylococcus aureus

Most common mechanism of seeding for adults

Traumatic

Most common mechanism of seeding for children

Hematogenous

Neoplasia of Bone

Name the bone tumor associated with the following clinical and pathologic findings:

Most common bone tumor

Metastatic tumors to bone

Most common primary bone tumor

Multiple myeloma

Most common benign tumor of bone

Osteochondroma or exostosis

Most common primary malignant tumor of bone

Osteosarcoma

Benign sessile tumor attached to the bone surface, usually affecting skull and facial bones

Osteoma

Benign tumor (2 cm) that is painful at night (due to excess PGE_2), relieved with aspirin and common in males 25 years old (y/o)

Osteoid osteoma

Malignant tumor typically occurring in the metaphyseal region prior to epiphyseal closure in patients 25 y/o

Osteosarcoma

Mushroom-shaped, laterally protruding tumor that may result from lateral displacement of the growth plate

Osteochondroma or exostosis

Benign tumor composed primarily of mature hyaline cartilage

Chondroma

Benign tumor composed of fibrous trabeculae of woven bone resembling Chinese characters

Fibrous dysplasia

Nodule of hyaline cartilage encased in reactive bone

Enchondroma

Malignant, painful, small round blue cell tumor of childhood occurring typically in the appendicular skeleton (may also affect ribs)

Ewing sarcoma/primitive neuroectodermal tumor (PNET)

Malignant tumor composed of multinucleated giant cells within a fibrous stroma, occurring in the epiphyses of long bones

Giant cell tumor of bone

Lacelike pattern of bone produced by tumor cells

Osteosarcoma

Homer-Wright pseudorosettes, onion skin appearance on x-ray

Ewing sarcoma/PNET

Malignant tumor of cartilage found in the central skeleton

Chondrosarcoma

Double bubble or soap bubble appearance on XR

Giant cell tumor of bone

Benign but painful bone tumor that appears as a radiolucent nidus surrounded by dense bone

Osteoid osteoma or osteoblastoma

Codman triangle on x-ray forms as tumor, causing periosteal elevation

Osteosarcoma

Onion skin appearance on x-ray

Ewing sarcoma

What is the most common genetic defect associated with Ewing sarcoma/PNET?

t(11;22)(q24;q12) translocation (85%) associated with an EWS-FLI1 fusion gene product

Mutation of what gene increases the risk of osteosarcoma by 1000 X x?

Rb gene

What malignancies are most likely to metastasize to bone?

Breast, lung, thyroid, kidney, and prostate (BLT with a Kosher pickle)

What pediatric disease is characterized by the triad of skull lesions, diabetes insipidus, and exophthalmos?

Hand-Schüller-Christian disease or histiocytosis X

What pediatric disease is characterized by polyostotic fibrous dysplasia, cafe au lait spots, precocious puberty, and other endocrine disorders?

McCune-Albright syndrome

Arthritis

Name the arthritic joint disease associated with the following clinical and pathologic findings:

Most common type of arthritis

Osteoarthritis

Most common type of infective arthritis and most common cause of arthritis in sexually active adults

Gonococcal arthritis

Anti-IgG Fc antibodies

Rheumatoid arthritis (RA); anti-IgG Fc antibodies are called rheumatoid factor

Subcutaneous rheumatoid nodules

RA

Heberden (DIP) and Bouchard (PIP) nodes

Osteoarthritis

PIP and MCP involvement

RA (Note: RA almost never affects DIP)

Most commonly affects great toe (podagra)

Gout

Presents as pain in weight-bearing joints after use, improves with rest

Osteoarthritis

Infrequent complication of psoriasis asymmetrically affecting DIP and PIP joints in the lower extremities

Psoriatic arthritis

Swan-neck and boutonniere deformity

RA

Chronic low back pain, rigidity, fixation of spine causing a condition referred to as bamboo spine

Ankylosing spondylitis

Infection causing migratory polyarthritis and erythema chronicum migrans; may lead to pericarditis and aseptic meningitis

Lyme disease

Arthritic joint disease associated with inflammatory bowel disease

Ankylosing spondylitis

Presents as morning stiffness improving with use, symmetric joint involvement, systemic symptoms

RA

Arthritis in the absence of systemic symptoms

Osteoarthritis

Extraskeletal manifestations of this arthritic disease include pulmonary fibrosis, aortic insufficiency, and cauda equina syndrome

Ankylosing spondylitis

Triad of conjunctivitis or anterior uveitis, urethritis, and arthritis

Reactive arthritis, previously know as Reiter syndrome (Remember: can’t see, can’t pee, can’t climb a tree)

Tophi (nodules of fibrous tissue) and crystals may be found on Achilles tendon or at external ear

Gout

Osteophyte formation at edge of articular surface and at sites of ligamentous attachment

Osteoarthritis

Filling of the joint space by granulation tissue (ie, a pannus)

RA

Frayed fragments of cartilage and osteophytes released into synovium forming “joint mice”

Osteoarthritis

Associated with hyperuricemia, thiazide diuretic use, and urate kidney stones

Gout

Eburnation of bone due to cartilage erosion

Osteoarthritis

Marginal erosion of subchondral bone

RA

Cystic changes in bones underlying affected joints

Osteoarthritis

Precipitation of urate crystals in joints resulting in an inflammatory response

Gout

Precipitation of calcium pyrophosphate dihydrate crystals in joints → inflammatory response

Pseudogout (aka calcium pyrophosphate deposition disease [CPPD])

Infective arthritis common in individuals with complement deficiencies; associated with ↑ susceptibility to meningitis

Gonococcal arthritis

Associated with deficiency of hypoxanthine guanine phosphoribosyl transferease (HGPRT)

Lesch-Nyhan syndrome (X-linked disease which may include gout as one of its manifestations)

Positively birefringent, rhomboid-shaped crystals

Pseudogout = Positively birefringent

Negatively birefringent, needle-shaped crystals in synovial fluid

Gout

Infective monoarticular arthritis typically causing knee pain and a pustular rash

Gonococcal arthritis

Infective polyarticular arthritis caused by Borrelia burgdorferi

Lyme disease

Monoarticular arthritis with gram-positive organisms on synovial fluid analysis

Nongonococcal septic arthritis

Stress, alcohol binge, or a large meal may precipitate an attack of this type of arthritis

Gout

Treatment for acute gout attack

Indomethacin (NSAID), Colchicine (use limited by GI side effects)

Treatment for chronic gout

Allopurinol (inhibits xanthine oxidase), probenecid (inhibits reabsorption of uric acid)

Anticytokine therapy for RA is directed at which two cytokines?

1. Interleukin (IL)-1

2. Tumor necrosis factor (TNF)

What is the factor produced by activated T cells and fibroblasts that promotes bone destruction by osteoclasts?

Receptor Activator of Nuclear Factor k B Ligand (RANKL), also known as TNF-related activation-induced cytokine (TRANCE)

What group of diseases is associated with high incidence (90%) in HLA-B27-positive patients?

Seronegative spondyloarthropathies (ankylosing spondylitis, reactive arthritis, arthritis associated with inflammatory bowel disease [IBD])

Name four extra-articular manifestations of RA:

1. Pleural and pericardial effusions

2. Acute vasculitis

3. Inflammatory lesions of lungs, pleura, myocardium, pericardium, peripheral nerves, and eyes

4. Amyloidosis (in severe, long-term disease)

What chemotactic factors are generated by urate crystal activation of complement?

C3a and C5a

How is tissue injury mediated in gout?

Release of lysosomal enzymes from neutrophils

Why are leukemia, multiple myeloma, and other neoplastic processes associated with gout?

High cell turnover releases uric acid and predisposes to an attack of gout.

What is the renal complication of longstanding gout?

Urate nephropathy

Which syndrome is characterized by cutaneous pigmentation, leg ulcerations, splenomegaly, neutropenia, and RA?

Felty syndrome

What two bacteria most commonly cause nongonococcal septic arthritis?

Staphylococcus aureus and Streptococcus spp.

CHAPTER 13

Behavioral Sciences

LIFE CYCLE

Development

At what age is an average child expected to do each of the following:

Hold his/her head up

3 months

Sit up without support

6 months

Crawl

9 months

Walk

12 months

Ride a tricycle

36 months (tricycle at 3 years)

Display stranger anxiety

7 months

Use a pincer grasp

9 months (Remember: an upside-down pincer grasp forms the number “9”)

Say their first word

12 months (1 word at 1 year)

Use two-word combinations

24 months (2 words at 2 years)

Use three-word sentences

36 months (3 words at 3 years)

Understand object permanence

12 to 24 months

Toilet training

30 to 36 months

“No” phase, repeated temper tantrums

24 months (address tantrums by ignoring behavior)

Show abstract reasoning (formal operations)

Adolescence/puberty

At what age are the following reflexes considered normal:

Babinski

0 to 12 months

Palmar

0 to 2 months

Rooting

0 to 3 months

Name the components of the Apgar score:

APGAR (0, 1, or 2 in each category)

Appearance/color (blue/pale, trunk pink, all pink)

Pulse (0, 100, >100)

Grimace (0, grimace, grimace + cough)

Activity/muscle tone (limp, some, active)

Respiratory effort (0, irregular, regular)

Determine the Apgar score for these patients:

Newborn with a pink trunk, heart rate (HR) = 50, a grimace and cough when stimulated, strong muscle tone, and an irregular respiratory effort

7

A blue newborn, HR = 30, a grimace when stimulated, appears limp, and has no respiratory effort

2

What is the definition of low birth weight?

Less than 2500 g

Name four sequelae of low birth weight:

1. Infections

2. Respiratory distress syndrome

3. Persistent fetal circulation

4. Necrotizing enterocolitis

What term describes the act of a child reverting to a more primitive mode of behavior due to stress?

Regression

Name four long-term effects of depriving affection from infants:

The 4 W’s:

1. Weak

2. Wordless

3. Wary

4. Wanting

What term describes depression in an infant due to sustained separation from the caregiver?

Anaclitic depression (results in impaired social, emotional, and physical development)

Name three findings that are suggestive of each type of abuse listed below:

Physical child abuse

1. Fractures at different stages of healing

2. Cigarette burns

3. Retinal hemorrhage/detachment (32% of kids 5 years old [y/o] are physically abused)

Sexual child abuse

1. Genital/anal trauma

2. STDs

3. UTIs (25% of kids 8 y/o are sexually abused)

Elder abuse

1. Evidence of depleted finances

2. Poor hygiene

3. Spiral fractures

Aging

Name the changes found in the elderly in each of the following categories:

Psychiatric

Depression and anxiety more common; ↑ suicide rate

Sexual

Men: slower erection/ejaculation, ↑ refractory period; women: vaginal shortening, thinning, and dryness

Note: sexual interest does not decrease.

Sleep patterns

↓ Rapid eye movement (REM), slow-wave sleep; ↑ sleep latency, awakenings

Cognitive

↓ Learning speed; intelligence stays the same

Name three conditions that would qualify normal bereavement as pathologic grief:

1. Prolonged grief (> 1 year)

2. Excessively intense grief (sleep disturbances, significant weight loss, suicidal ideations)

3. Grief that is delayed, inhibited, or denied

Name the Kübler-Ross stages of dying:

Denial, anger, bargaining, depression, acceptance. Note: one or more stages can occur at once and not necessarily in this order.

PHYSIOLOGY

Sleep

Name the sleep stage associated with each of the following descriptions:

Light sleep, peacefulness, ↓ HR and BP

Stage 1

Deepest non-REM sleep; sleepwalking, bedwetting

Stages 3 and 4

Deeper sleep; EEG shows sleep spindles and K-complexes; occupies ~half of total sleep time in young adults

Stage 2

Beta waves (↑ frequency, ↓ amplitude) only

Awake (eyes open) and alert REM

Beta, alpha, and theta waves → “sawtoothing”

REM

Alpha waves

Awake (eyes closed)

Dreaming, loss of motor tone, ↑ brain O_2use, erections; occurs every 90 minutes

REM

Delta (slow) waves(↓ frequency, ↑ amplitude)

Stages 3 and 4

Name the sleep disorder described in each of the following statements:

Abnormal behavior associated with sleep or sleep-wake transitions (eg, sleep terrors, enuresis, somnabulism)

Parasomnia

Disturbance in amount, quality, or timing of sleep (eg, insomnia, narcolepsy)

Dyssomnia

Nighttime respiratory effort against an impeded airway, resulting in 10-second lapses in breathing and chronic fatigue

Obstructive sleep apnea

What is a useful drug for night terrors and sleepwalking?

Benzodiazepines (shortens stage 4 sleep)

Which drug treats enuresis in children by decreasing stage 4 sleep?

Imipramine

What is the main neurotransmitter involved in REM sleep?

Acetylcholine (ACh)

Name four physiologic changes that occur in REM sleep:

1. Increased and variable pulse

2. Increased and variable BP

3. Penile/clitoral tumescence

4. Rapid eye movements

Name four clinical findings of narcolepsy:

1. Sleep paralysis (brief paralysis upon awakening)

2. Hypnagogic (go ing to sleep) and hypnopompic (waking) hallucinations

3. ↓ REM latency (sleep episodes all start in REM)

4. Cataplexy (sudden loss of muscle tone, especially with extreme emotion)

How is narcolepsy treated?

Stimulants (eg, amphetamines), scheduled naps

What three sleep pattern changes are typical of depressed patients?

1. Reduced slow-wave sleep

2. ↓ REM latency

3. “Terminal insomnia” (early-morning awakenings)

Sexuality

Name the four stages of the sexual response cycle:

1. Excitement

2. Plateau

3. Orgasm

4. Resolution

Name three possible etiologies of sexual dysfunction:

1. Drugs (eg, selective serotonin reuptake inhibitors [SSRIs], ethanol [ETOH], antihypertensives)

2. Disease (eg, depression, diabetes, myocardial infarction [MI])

3. Psychologic (eg, aversion, hypoactive desire, premature ejaculation)

What disorder of sexual function is characterized by painful spasm of the outer one-third of the vagina during intercourse or pelvic examination?

Vaginismus

What is a paraphilia?

Unusual sexual activities or sexual desire for unusual objects (eg, pedophilia, voyeurism, and so forth)

Behavioral Neurochemistry

For each of the following diseases, describe the associated neurotransmitter activity:

Schizophrenia

↑ Dopamine (DA) and 5-hydroxytryptamine (5-HT)

Depression

↓ Norepinephrine (NE) and 5-HT

Anxiety

↑ NE, ↓ γ-aminobutyric acid (GABA), and 5-HT

Alzheimer dementia

↓ ACh in Alzheimer dementia

Parkinson disease

↓ DA

Huntington disease

↓ GABA and ACh

SUBSTANCE ABUSE

What is the lifetime prevalence of substance abuse/dependence?

13%

How is “dependence” defined?

Withdrawal occurs if substance is stopped and patient has tolerance to substance.

Excluding tobacco and caffeine, what is the most commonly abused substance?

Alcohol

What is a short, useful alcoholism screening tool?

“CAGE” questions

Have you felt the need to Cut down?

Have you ever felt Annoyed by criticism of your drinking?

Have you ever felt Guilty about drinking?

Have you ever had an Eye opener?

What is the major complication of alcohol withdrawal and when is it most likely to occur?

Delirium tremens (DTs); peak occurrence is 2 to 7 days. Note: DTs are a medical emergency.

What is the mortality rate of DTs?

15% to 20%

Name three gastrointestinal (GI) complications of alcoholism:

1. GI bleeding (from ulcers, gastritis, esophageal varices, or Mallory-Weiss tears)

2. Pancreatitis

3. Liver disease

Which syndrome of anterograde amnesia, confabulations, ataxia, and nystagmus results from thiamine deficiency in chronic alcoholics?

Wernicke-Korsakoff syndrome— Remember: Wobbly-Konfabulations (associated with bilateral mammillary body necrosis)

What am I high on?

Central nervous system (CNS) and respiratory depression, euphoria, pinpoint pupils, nausea, and ↓ GI motility

Opioids; inspect for track marks along veins

Psychomotor agitation, dilated pupils, euphoria, ↑ HR and BP, prolonged wakefulness and attention, delusions, ↑ pain threshold

Amphetamines

All of the above, plus tactile hallucinations, angina, and sudden cardiac death

Cocaine

Belligerence, psychomotor agitation, nystagmus, ataxia, homicidality, psychosis, delirium, ↑ HR, and fever

Phencyclidine hydrochloride (PCP)

Delusions, visual hallucinations, postuse “flashbacks”

Lysergic acid diethylamide (LSD)

Euphoria, ↑ appetite, dry mouth, paranoid delusions, erythematous conjunctiva

Marijuana

Disinhibition, emotional lability, slurred speech, ataxia, blackouts, coma

Alcohol

What is the drug of choice for opioid overdose?

Naloxone and naltrexone (competitively inhibit opioid receptors)

Which drug is used for heroin detoxification?

Methadone (long-acting oral opioid)

PSYCHOLOGY

What are the three parts of Freud’s structural theory of the mind?

1. Id

2. Superego

3. Ego

Which of these parts is described by the following statements:

Represents conscience and moral values

Superego

Controlled by primitive wishes and pleasures; represents instinctive sexual and aggressive drives

Id

Bridges unconscious mind and external world

Ego

What Freudian term encompasses repressed sexual feelings of a child for the opposite-sex parent, plus a rivalry with the same-sex parent?

Oedipus complex

What type of insight therapy, developed by Freud, may be useful for chronic personality problems?

Psychoanalysis

What describes a scenario in which a patient’s unconscious feelings from past relationships are experienced in the present relationship with the physician?

Transference reaction

What reaction occurs when the physician unconsciously reexperiences feelings about his/her parents (or other important persons) with the patient?

Countertransference reaction

Name the four mature ego defense mechanisms:

1. Suppression

2. Altruism

3. Sublimation

4. Humor

Note: defense mechanisms are automatic and unconscious.

Name the type of learning that is described by each of the following statements:

Reflexive response is elicited by a learned stimulus

Classical conditioning

Tendency of an organism to follow the first thing they see after birth

Imprinting

Behavior is eliminated when not reinforced

Extinction

Behavior is determined by its consequences

Operant conditioning

Unwanted behavior is paired with painful stimulus

Aversive conditioning

Type of classical conditioning where the subject learns that it cannot escape a painful stimulus

Learned helplessness

In what type of reinforcement schedule is a reward presented after a random, unpredictable number of responses?

Variable ratio (slowest extinction when not rewarded); example = slot machine

In what type of reinforcement schedule is a reward presented after every response?

Continuous (rapid extinction when not rewarded); example = vending machine

Criteria for mental retardation begin below what IQ level?

Less than 70 (2 SD below the mean of 100)

PSYCHIATRY

Name the type of amnesia described below:

Inability to remember things that occurred before insult to CNS

Retrograde amnesia

Inability to remember things that occurred after a CNS injury → no new memory formation

Anterograde amnesia

Complication of electroconvulsive therapy (ECT)

Retrograde amnesia

Thiamine deficiency causing bilateral mammillary body necrosis; seen in alcoholics

Korsakoff (anterograde) amnesia

Delirium or dementia?

Waxing and waning level of consciousness

Delirium

Rapid onset; transient

Delirium

Characterized by memory loss

Dementia (think deMEMtia)

Associated with disturbances in sleep wake cycle

Delirium

Often irreversible

Dementia

Associated with changes in sensorium Delirium (hallucinations and illusions)

Delirium

Name four major causes of delirium:

“HIDE”:

1. Hypoxia

2. Infection (often UTIs)

3. Drugs

4. Electrolyte abnormalities

What is the most common etiology for dementia?

Dementia of Alzheimer type (DAT) = 70% to 80% of cases

Name some other etiologies for dementia:

“DEMENTIASS”

Degenerative diseases (Parkinson, Huntington)

Endocrine (thyroid, pituitary, parathyroid)

Metabolic (electrolytes, glucose, hepatorenal dysfunction, ETOH)

Exogenous (CO poisoning, drugs, heavy metals)

Neoplasia

Trauma

Infection (encephalitis, meningitis, cerebral abscess, syphilis, prion diseases, HIV, Lyme disease)

Affective disorders (depression may mimic dementia)

Stroke (multi-infarct dementia, ischemia, vasculitis). Note: vascular causes ~10% of dementias

Structure (normal-pressure hydrocephalus [NPH]).

Note: NPH is one of the few reversible causes of dementia.

Mood Disoders

Name the nine key features of major depressive disorder (MDD):

“SIG E CAPSS”

1. Sleep changes (insomnia/hypersomnia)

2. Inability to experience pleasure, Interest decreases

3. Guilt or feelings of worthlessness

4. Energy ↓ (fatigue)

5. Concentration ↓, indecisiveness increases

6. A ppetite disturbance with weight change (> 5% body weight in 1 month)

7. Psychomotor changes (agitation or retardation)

8. Suicidal ideations

9. Sadness (depressed mood for most of day)

What features are required to make the diagnosis of MDD?

Two episodes (involving five of the above nine including # 1 or 2) of impaired functioning for 2 weeks, separated by 2 months

What is the suicide rate in MDD?

Approximately 15% to 30%

Name the risk factors for suicide:

“SAD PERSONS”

Sex—male (women > attempts; men > actual suicides)

Age (↓ 15-24 and the elderly)

Depression

Previous attempts = #1 risk factor

Ethanol

Rational thought

Sickness

Organized plan

No spouse

Social support lacking

What is the first-line pharmacotherapy for MDD?

SSRIs

Name two other alternate pharmacotherapies:

1. Tricyclic antidepressants (TCAs)

2. Monoamine oxidase inhibitors (MAOIs)

What is a safe, effective treatment for refractory MDD?

ECT

What is the distinctively abnormal, elevated, expansive mood that lasts > 1 week or is severely impairing (eg, requiring hospitalization)?

Manic episode

What are the seven key features of mania?

“DIG FAST” (at least three of the following for diagnosis):

1. Distractibility

2. Insomnia

3. Grandiosity

4. Flight of ideas or racing thoughts

5. Psychomotor Agitation

6. Speech that is pressured (hyperverbal)

7. Thoughtlessness (↑ pleasurable activities with ↑ consequences)

Name the following mood disorders:

Chronic disorder > 2 years (alternating hypomania and mild depression); no period of euthymia > 2 months and no significant impairment

Cyclothymia

Less severe features for several days that are not impairing; no psychotic features

Hypomania

History of major depressive episodes and at least one hypomanic episode

Bipolar II disorder

Manic episodes that often alternate with depressive episodes

Bipolar I disorder

Somatoform Disorders

Name the somatoform disorder associated with each of the following descriptions:

Preoccupation with an imagined physical defect, causing significantly impaired social and occupational functioning

Body dysmorphic disorder

Multiple, unrelated physical complaints leading to excessive medical attention seeking and severely impaired functioning

Somatization disorder (requires four pain, two GI, one sexual/GU, and one pseudoneurologic complaints). Note: cannot be intentional or fake

Prolonged preoccupation with concerns of having a serious illness (despite negative medical work-ups) and exaggerated attention to bodily or mental sensations

Hypochondriasis

Conscious simulation of physical or psychologic illness solely to receive attention from medical personnel

Factitious disorder (Munchausen syndrome). Note: technically not a somatoform disorder because it is intentional

Intentionally simulating illness for personal gain (usually financial)

Malingering. Note: also not a somatoform disorder; suspect in cases involving litigation

Sudden onset of motor/sensory neurologic disorder following traumatic emotional event

Conversion disorder

Name the type of gain associated with each of the following descriptions:

Interpersonal or social advantages gained indirectly from illness

Secondary gain

Benefits of illness on the patient’s internal psychic economy

Primary gain

Advantage gained by the caretaker

Tertiary gain

Name the type of anxiety disorder associated with each of the following:

Maladaptive reaction to environmental or psychologic stress that interferes with functioning and does not remit after the stress ends

Adjustment disorder

Marked, persistent fear of an object/situation that is excessive and unreasonable → stimulus is avoided; patient has insight (treat by exposure therapy)

Specific phobia

Occurs after a person is subjected to a traumatic event; lasts >1 month; may be debilitating

Posttraumatic stress disorder (PTSD)

Symptoms of PTSD that occur within 4 weeks of the stressor and last 4 weeks

Acute stress disorder

Moments of intense fear characterized by palpitations, choking sensation, GI upset, perspiration, chest pain, and chills

Panic disorder

Excessive worrying for the majority of days over the past 6 months that causes significant impairment

Generalized anxiety disorder

Recurrent, intrusive, senseless thoughts and impulses; plus the repetitive behaviors driven by the will to decrease the anxiety caused by them

Obsessive-compulsive disorder (OCD)

Name the dissociative disorder characterized by the following statements:

Two or more separate personalities in one individual; ↑ in women and sexually abused

Dissociative identity disorder (formerly multiple personality disorder)

A complete, often transient, inability to remember important personal information

Dissociative amnesia

Amnesia plus sudden wandering from home and taking on a different identity

Dissociative fugue

Psychoses

Give the appropriate term for each of the following psychotic symptoms:

False belief or wrong judgment held with conviction despite incontrovertible evidence to the contrary

Delusion

False perception of an actual external stimulus

Illusion

Thought disorder whereby ideas are not logically connected to those that occur before or after

Loose association

Misinterpreting others’ actions or environmental cues as being directed toward one’s self when, in fact, they are not

Ideas of reference

Subjective perception of an object or event when no such external stimulus exists

Hallucination

Name the psychotic disorder characterized by each of the following findings:

Two or more psychotic symptoms and disturbed behavior for > 6 months; results in impaired functioning

Schizophrenia

Psychotic symptoms lasting 1 to 6 months

Schizophreniform disorder

Psychotic symptoms lasting > 1 day, but 1 month (often with obvious precipitating psychosocial stressor)

Brief psychotic disorder

Fixed, nonbizarre delusional system; without other thought disorders or impaired functioning

Delusional disorder

Symptoms of major mood disorder as well as of schizophrenia (with psychotic features occurring before mood disturbance); chronic social and occupational impairment

Schizoaffective disorder

Clouded consciousness, predominantly visual hallucinations, often occurring in inpatient setting

Psychotic disorder due to a general medical condition

Adopting the delusional system of a psychotic person

Shared psychotic disorder (Folie-à-deux)

Name the five subtypes of schizophrenia:

1. Disorganized

2. Catatonic

3. Paranoid

4. Undifferentiated

5. Residual

Give two examples of positive symptoms of schizophrenia:

1. Hallucinations

2. Delusions

Positive symptoms respond best to what type of drugs?

Typical antipsychotics

Give four examples of negative symptoms that are characteristic of schizophrenia:

The 4 A’s:

1. Affect flat

2. Alogia

3. Anhedonia

4. Avolition

Negative symptoms respond best to what type of drugs?

Atypical antipsychotics. Note: worse prognosis if negative symptoms predominate

Childhood Disorders

Name the disorder of childhood described by each of the following statements:

Repetitive behaviors (in patient 18 y/o) that violate social norms; may exhibit physical aggression, cruelty to animals, vandalism, and robbery, along with truancy, cheating, and lying

Atypical antipsychotics. Note: worse actions)

Recurrent pattern of negativistic, hostile, and disobedient behavior toward authority figures; loss of temper and defiance (but not theft or lying)

Oppositional defiant disorder (predominantly words)

Developmentally inappropriate degrees of inattention, impulsiveness, and hyperactivity at home, in school, and in social situations

Attention deficit hyperactivity disorder (ADHD)

Pervasive developmental disorder (PDD) with stereotyped movements and nonprogressive impairments in social interactions, communication, and behavior

Autism

Progressive syndrome of autism, dementia, ataxia, and purposeless hand movements; regression of development; mainly in girls

Rett syndrome

PDD with severe impairment in social skills and repetitive behaviors, leading to impaired social and occupational functioning but without significant delays in language development

Asperger disorder

Personality Disorders

List the three cluster A personality disorders:

“Weird”

1. Paranoid

2. Schizoid

3. Schizotypal

List the four cluster B personality disorders:

“Wild”

1. Histrionic

2. Borderline

3. Antisocial

4. Narcissistic

List the three cluster C personality disorders:

“Worried”

1. Avoidant

2. Obsessive-compulsive

3. Dependent

Name the personality disorder characterized by each of the following statements:

Socially inhibited, sensitive to rejection, feels inferior

Avoidant (C)

Peculiar appearance, interpersonal awkwardness, “magical” or odd thought patterns, no psychosis

Schizotypal (A)

Impulsive, unstable mood, chaotic relationships, feels empty and alone, self-mutilation, females >> males

Borderline (B)

Sense of entitlement, grandiosity, lacks empathy for others, insists on special treatment when ill

Narcissistic (B)

Suspicious and distrustful, uses projection as primary defense mechanism

Paranoid (A)

Lacks self-confidence, submissive, and clingy

Dependent (C)

Unable to maintain intimate relationships, extroverted, melodramatic, sexually provocative

Histrionic (B)

Disregards and violates rights of others, criminality, males > females; if 18 y/o = conduct disorder

Antisocial (B)

Lifelong pattern of voluntary social withdrawal, no psychosis, shows minimal emotions

Schizoid (A)

PHARMACOLOGY—PSYCHOPHARMACOLOGY

For each of the following drugs, provide:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects and unique toxicity (TOX) (if any)

Antidepressants

TCAs (imipramine, clomipramine, amitriptyline, desipramine, nortriptyline, doxepin, amoxapine)

MOA: prevents reuptake of NE and 5-HT

IND: depression, enuresis (imipramine), depression in elderly (nortriptyline), OCD (clomipramine), depression with psychotic features (amoxapine), neurologic pain

TOX: sedation (desipramine is least sedating), anticholinergic effects, lethal in overdose → respiratory depression, hyperpyrexia, and Tri-C’s: Cardiac arrhythmia, Convulsions, Coma

SSRIs (fluoxetine, paroxetine, sertraline, citalopram, fluvoxamine, escitalopram)

MOA: selectively blocks reuptake of 5-HT (usually requires 2-3 weeks to take effect)

IND: depression, premenstrual syndrome (fluoxetine), OCD (fluvoxamine)

TOX: agitation, insomnia, sexual dysfunction, “serotonin syndrome” with MAOIs (muscle rigidity, hyperthermia, cardiovascular collapse)

Bupropion

MOA: heterocyclic agent, mechanism not well known

IND: depression, smoking cessation

TOX: agitation, seizures, insomnia (↓ sexual side effects)

Trazodone

MOA: mainly inhibits serotonin reuptake

IND: depression

TOX: postural hypotension, sedation, priapism

Venlafaxine

MOA: inhibits 5-HT and NE reuptake

IND: depression, generalized anxiety disorder

TOX: stimulant effects, minimal effects on P-450

Mirtazapine

MOA:5-HT_2 receptor antagonist and α_2-antagonist →↑ NE and 5-HT release

IND: depression

TOX: sedation, ↑ appetite, ↑ cholesterol

MAOIs (TIP: T ranylcypromine, I socarboxazid, phenelzine)

MOA: nonselective MAOIs

IND: atypical depressions, anxiety disorders, pain disorders, eating disorder

TOX: hypertensive crisis with tyramine or meperidine ingestion, “serotonin syndrome” with SSRIs

Lithium

MOA: prevents generation of inositol triphosphate (IP_3) and diacylglycerol (DAG) 2° messenger systems

IND: bipolar disorder (prevents and treats acute mania)

TOX: hypothyroidism, nephrogenic DI, teratogenesis (Ebstein anomaly)

Carbamazepine

MOA: blocks sodium channels and inhibits action potentials

IND: bipolar disorder, mixed episodes, and rapid cycling form

TOX: hematologic SEs, elevated LFTs, teratogenesis (neural tube defects)

Valproic acid

MOA: increases CNS levels of GABA

IND: bipolar disorder, mixed manic episodes, and rapid cycling form

TOX: hepatotoxicity, thrombocytopenia, teratogenesis (neural tube defects)

Antipsychotics

What is the name for the stereotyped oral-facial movements that occur as a result of long-term antipsychotic use?

Tardive dyskinesia

Describe the chronology of extrapyramidal side effects from neuroleptic medications:

Rule of 4’s: 4 hours—acute dystonia, 4 days—akinesia, 4 weeks—akathesia, 4 months—tardive dyskinesia (usually irreversible)

What is the characteristic triad of neuroleptic malignant syndrome (NMS)?

Muscle rigidity, autonomic instability, and hyperpyrexia

What is the treatment for NMS?

Dantrolene and DA agonists

For each of the following drugs, provide:

1. The mechanism of action (MOA)

2. Indication(s) (IND)

3. Significant side effects and unique toxicity (TOX) (if any)

Typical antipsychotics—high potency (haloperidol, perphenazine, trifluoperazine)

MOA: block D_2 DA receptors (less blockade of α_2, muscarinic, and histaminic receptors)

IND: schizophrenia, psychosis (especially positive symptoms)

TOX:↑ neurologic (eg, extrapyramidal) SEs, NMS, tardive dyskinesia, Parkinsonism, hyperprolactinemia

Typical antipsychotics—low potency (chlorpromazine, thioridazine)

MOA: block D_2 DA receptors (more blockade of α_2, muscarinic, and histaminic receptors)

IND: schizophrenia, psychosis

TOX:↓ neurologic SEs, ↑ anticholinergic and endocrine SEs; cardiac conduction defects and retinal pigmentation (thioridazine), corneal and lenticular deposits (chlorpromazine)

Atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine)

MOA: block 5-HT_2; block D_4 and D_1 > D_2 receptors

IND: schizophrenia, psychosis (especially negative symptoms); OCD/anxiety disorder (olanzapine)

TOX:↓ anticholinergic and extrapyramidal symptoms (EPS); metabolic syndrome (hyperlipidemia, glucose intolerance), agranulocytosis (clozapine)

MEDICAL ETHICS

What are four key components to informed consent?

The patient must:

1. Understand the health implications of their diagnosis

2. Be informed of risks, benefits, and alternatives to treatment

3. Be aware of outcome if they do not give their consent

4. Have the right to withdraw consent at any time

Name four exceptions to informed consent:

1. Patient not legally competent to make decisions

2. In an emergency (implied consent)

3. Patient waives the right to informed consent

4. Therapeutic privilege—withholding info that would severely harm the patient or undermine decision-making capacity if revealed

What are five situations in which parent/legal guardian consent is not required to treat a minor?

1. Emergencies

2. STDs

3. Prescription of contraceptives

4. Treatment of ETOH/drug treatment

5. Care during pregnancy

What four criteria qualify a minor as emancipated?

1. Self-supporting

2. In the military

3. Being married

4. Having children that they support

What type of directive is based on the incapacitated patient’s prior statements and decisions?

Oral advance directive (substituted judgment standard)

What type of written advance directive gives instructions for the patient’s future health care should he/she become incompetent to make decisions?

Living will

What type of document allows the patient to designate a surrogate to make medical decisions in case the patient loses decision-making capacity?

Durable power of attorney

Name the ethical responsibility of the physician described by each of the following statements:

Requires physicians to “do no harm”

Nonmaleficence

Requires physicians to act in the best interests of the patient

Beneficence (may conflict with patient autonomy)

Demands respect for patient privacy and autonomy

Confidentiality

Name five exceptions to confidentiality:

1. Suspected child and/or elder abuse

2. Suicidal/homicidal patient

3. Impaired automobile driver

4. Specific infectious diseases—physician duty to report to public officials or individuals at risk

5. Tarasoff decision-law requiring physician to directly inform/protect potential victim from harm

What elements are required in order to prove a malpractice claim?

The “4 D’s”: must prove that the physician showed Deriliction (deviation from standard of care) of a Duty that caused Damages Directly to the patient

What is the legal standard of death?

Failure to meet cardiorespiratory criteria and irreversible cessation of all brain functions (including brainstem)

BIOSTATISTICS

For each description, name the proper term and the equation used to calculate the value described below:

Probability that a person without the disease will be correctly identified

Specificity TN/(TN + FP)

Probability that a person who tests positive actually has the disease

Positive predictive value TP/(TP + FP)

Probability that a person who has a disease will be correctly identified

Sensitivity TP/(TP + FN)

Total number of cases in a population at any given time

Prevalence TP + FN/(entire population)

Number of new cases that arise in a population over a given time interval

Incidence Prevalence × duration of disease (approximately)

Used in case-control studies to approximate the relative risk if the disease prevalence is too high

Odds ratio TP × TN/FP × FN

Used in cohort studies to compare incidence rate in exposed group to that in unexposed group

Relative risk (TP/[TP + FP])/(FN/[FN + TN])

Probability that patient with a negative test actually has no disease

Negative predictive value TN/(FN + TN)

How are incidence and prevalence related?

Incidence × disease duration = prevalence

Prevalence > incidence for chronic diseases; prevalence = incidence for acute diseases

What quality is desirable for a screening tool?

High sensitivity (SNOUT—SeNsitivity rules OUT)

What quality is desirable for a confirmatory test?

High specificity (SPIN—Specificity rules IN)

Name four ways to reduce bias:

1. Use of placebo

2. Blinded studies (single, double)

3. Crossover studies (each subject is own control)

4. Randomization

Name the type of statistical distribution described below:

Asymmetry with tail to the right

Positive skew

Two peaks

Bimodal

Scores cluster in the high end

Negative skew

Bell-shaped

Normal (Gaussian)

What percent of the area under a normal curve falls within 1, 2, and 3 standard deviations (SD) of the mean?

68% (1 SD), 95% (2 SD), 99.7% (3 SD)

How is standard error of the mean (SEM) calculated?

/square root of sample size

Name the term for each of the following descriptions:

Refers to the reproducibility of a test

Reliability

Refers to the appropriateness of a test (whether the test measures what it is supposed to)

Validity

Absence of random variation in a test; consistency and reproducibility of a test

Precision

Closeness of a measurement to the truth

Accuracy

Test that compares the difference between two means

t-test

Test that analyzes the variance of three or more variables

Analysis of variance (ANOVA)

Test that compares percentages or proportions

X^2 (chi-squared test)

Absolute value that indicates the strength of a relationship

r (always between -1 and 1)

Observational study where the sample is chosen based on presence/absence of risk factors

Cohort study (eg, prospective, historical)

Experimental study comparing benefits of two or more alternative treatments

Clinical trial

Observational study where the sample is chosen based on disease presence/absence

Case-control study (usually retrospective)

Assembling data from multiple studies to achieve great statistical power

Meta-analysis

Hypothesis postulating that there is no difference between groups

Null hypothesis (H_0)

Error of mistakenly rejecting H_0 (stating that there is a difference when there really is not)

Type I error (α)

Error of failing to reject H_0 (stating there is no difference when there really is)

Type II error (β)

Probability of rejecting H_0 when it is in fact false

Power (1-β)

Probability of making an α error

P value

PUBLIC HEALTH/EPIDEMIOLOGY

Name four reportable STDs:

1. Gonorrhea

2. Syphilis

3. Hepatitis B

4. Acquired immunodeficiency syndrome (AIDS) (nonreportable = HIV, chlamydia, genital herpes)

What is the leading cause of mortality in each of the following age groups:

1 y/o

Congenital anomalies

1 to 14 y/o

Unintentional injuries

15 to 24 y/o

Unintentional injuries (mostly car accidents)

25 to 64 y/o

Cancer (#1 lung, #2 breast/prostate, #3 colon)

65 years and older

Heart disease

What is 1° disease prevention?

Aims to prevent disease occurrence (eg, vaccination, education)

What is 2° disease prevention?

Early detection of disease; screening programs

What is 3° disease prevention?

Reduces disability resulting from disease (eg, physical therapy for stroke)

What is the current definition of “obese”?

BMI> 30, BMI> 25 is overweight

Approximately what percentage of the US population is obese?

~30%, > 50% overweight

What is the divorce rate in the United States?

~50%

Name three risk factors for divorce:

1. Teenage marriage

2. Mixed religions

3. Low SES. Note: peaks during second and third years

What is the criterion to qualify for hospice care?

Medically anticipated death within 6 months

What federal program addresses health care needs of the elderly?

MedicarE (Elderly)

What federal and state program addresses health care needs of the underprivileged?

MedicaiD (Destitute)

What 1996 law helps to protect rights to health coverage during events such as changing or losing jobs, pregnancy, moving, or divorce?

Health insurance portability and accountability act (HIPAA)

CHAPTER 14

Make the Diagnosis

NUTRITION

1-year-old (y/o) impoverished child presents with lethargy and poor wound healing; physical examination (PE): low-grade fever, pallor, oral mucosal petechiae, and bleeding gums.

Scurvy

50-y/o with history of (h/o) long-term treatment of psoriasis with methotrexate presents with nausea and fatigue; PE: within normal limits (WNL); workup (W/U): MCV > 100, hypersegmented neutrophils, and normal vitamin B_12 levels.

Folic acid deficiency

42-y/o alcoholic presents with ataxia and shortness of breath (SOB); PE: nystagmus, cardiomegaly with flow murmur, ↓ DTRs, ↓ peripheral sensation, and hepatomegaly.

Beriberi

48-y/o Scandinavian woman presents with weakness, ataxia, and SOB; PE: ↓ balance and vibratory sensation in lower extremities; W/U: MCV > 100, hypersegmented PMNs, and positive Schilling test.

Pernicious anemia

MICROBIOLOGY AND INFECTIOUS DISEASES

4-y/o with a superficial skin infection consisting of erythematous pustules with honey-colored scabs.

Impetigo, most commonly due to Staphylococcus aureus

6-y/o child with poor hygiene presents with complaints of severe perianal itching that is worse at night; W/U: a “scotch tape test” reveals eggs visualized under the microscope.

Pinworm infection

36-y/o man presents with flu-like symptoms since moving to a farm in Ohio 2 months ago; PE: fever and generalized lymphadenopathy; chest x-ray (CXR): bilateral hilar adenopathy.

Histoplasmosis

Patient with recent h/o antibiotic use presents with fever, bloody diarrhea, and abdominal pain; PE: tender abdominal examination, guiaic + stool; complete blood count (CBC): leukocytosis; colonoscopy: tan nodules seen attached to erythematous bowel wall with superficial erosions.

Pseudomembranous colitis (Clostridium difficile colitis)

18-y/o student returns to clinic with a rash after being treated with ampicillin for fever and sore throat; PE: tonsilar exudates and enlarged posterior cervical lymph nodes; W/U: ↑ lymphocytes and ⊕ heterophile antibody test.

Infectious mononucleosis due to Epstein Barr virus (EBV)

28-y/o with h/o treatment for 2° syphilis 5 hours ago with intramuscular (IM) penicillin presents with fever, chills, muscle pain (myalgias), and headache.

Jarisch-Herxheimer reaction

33-y/o northern European with h/o eating raw fish presents with shortness of breath and weakness; W/U: megaloblastic anemia, operculated eggs on stool examination.

Diphyllobothrium latum infection (with vitamin B_12 deficiency)

17-y/o swimmer presents with pain and discharge from the left ear; PE: movement of tragus is extremely painful; Gram stain shows gram-negative rods.

Otitis externa (most likely due to Pseudomonas aeruginosa)

10-y/o with sickle cell disease and recent h/o prodromal illness presents with sudden-onset pallor, fatigue, and tachycardia; CBC: pancytopenia with reticulocytes 1%.

Parvovirus B19 aplastic crisis

44-y/o parrot owner presents with fever, chills, headache, and cough; PE: Horder spots on abdomen and splenomegaly; CXR: bilateral, interstitial infiltrates.

Psittacosis

33-y/o epileptic with recent loss of consciousness presents with fever and cough with purulent, putrid sputum; W/U: Gram stain reveals mixed oral flora; CXR: consolidation of right lower lobe.

Aspiration pneumonia

50-y/o man presents with a fever of unknown origin. One month ago he had a dental procedure. He has a history of rheumatic heart disease; PE: significant for a heart murmur, splinter hemorrhages, Janeway lesions, Roth spots, and Osler nodes.

Subacute bacterial endocarditis due to Streptococcus viridans

9-y/o with recent viral prodomal illness presents to ER vomiting and lethargic after being given aspirin for fever; W/U: impaired liver function; computed tomography (CT): cerebral edema.

Reye syndrome

15-y/o new pet owner presents with painful axillary lumps and fever; PE: cervical lymphadenopathy.

Catscratch disease

2-month-old with maternal h/o rash and flu in first trimester presents with a rash and failure to attain milestones; PE: microcephaly, cataracts, jaundice, continuous machinery-like murmur at left upper sternal border, and hepatosplenomegaly (HSM).

Congenital rubella

8-y/o from Connecticut presents with fever, rash, headache, and joint pain after playing in the woods; PE: distinctive macule with surrounding 6 cm target-shaped lesion.

Lyme disease

35-y/o man with h/o urinary catheterization presents with fever, chills, dysuria, and perineal pain; PE: swollen, tender, hot prostate; urinalysis (UA): WBCs and culture ⊕ for Escherichia coli.

Acute bacterial prostatitis

38-y/o man with h/o asthma presents with recurrent fever, wheezing, and cough productive of brown mucous plugs; CBC: eosinophilia, high IgE titers; CXR: mucoid impaction of dilated central bronchi.

Allergic bronchopulmonary aspergillosis

6-y/o unvaccinated child presents with rhinorrhea, cough, conjunctivitis; PE: oral lesions are noted which are bluish with an erythematous border.

Measles

37-y/o man with a recent h/o upper respiratory infection (URI) presents with fever and severe chest pain; PE: friction rub and Kussmauls sign; W/U: ↑ ESR, normal cardiac enzymes, and diffuse ST elevations on ECG.

Acute pericarditis

4-y/o presents with barking cough, fever, and rhinorrhea; PE: respiratory distress and tachypnea; x-ray of soft tissues of neck reveals “steeple sign.”

Croup

18-y/o sexually active woman with h/o treatment for purulent vaginitis presents with a fever and tenderness, warmth, and swelling of her right knee.

Gonococcal arthritis

Newborn presents with rash and maternal h/o intrauterine growth retardation (IUGR) and flu during first trimester; PE: petechial rash, chorioretinitis, microcephaly, ↓ hearing, and HSM; W/U: ↓ platelets and periventricular calcifications on head CT.

Congenital cytomegalovirus (CMV)

25-y/o West Virginian man presents with fever, headache, myalgia, and a petechial rash that began peripherally but now involves his whole body, even his palms and soles; W/U: shows +OX19 and OX2 Weil-Felix reaction.

Rocky Mountain spotted fever

10-y/o presents with fevers and a pruritic rash spreading from the trunk to the arms; PE: vesicles of varying stages.

Varicella

29-y/o athlete presents with a red, pruritic skin eruption with an advancing peripheral, creeping border on the forearm; W/U shows septate hyphae in KOH scraping.

Tinea corporis (ringworm)

8-y/o presents with fever, photophobia, stiff neck, and headache; PE: ⊕ Kernig and Brudzinski signs; lumbar puncture shows normal glucose and ↓ WBCs.

Viral meningitis

21-y/o presents with nausea, vomiting, bloating, and foul-smelling stools on returning from a camping trip; W/U: binucleate, flagellated trophozoites in stool.

Giardiasis

14-y/o adolescent boy with h/o recent travel to Mexico now presents with jaundice and dark yellow urine; PE: icterus and firm hepatomegaly; W/U: ↑ bilirubin (BR), ↑ LFTs with alanine transaminase (ALT) > aspartate transaminase (AST).

Hepatitis A infection

26-y/o sexually active, native Caribbean presents with painless, beefy-red ulcers of the genitalia and inguinal swelling; W/U: Donovan bodies on Giemsa-stained smear.

Granuloma inguinale

Patient presents with sudden onset of severe watery diarrhea, vomiting, and abdominal discomfort 4 hours after eating potato salad at a picnic; the symptoms resolve spontaneously within 24 hours.

Staphylococcus aureus-induced diarrhea

6-y/o with recent h/o sore throat presents with multiple joint pain and swelling, fever, and SOB; PE: erythema marginatum, subcutaneous nodules, and apical systolic murmur; W/U: ↑ ESR and CRP.

Acute rheumatic fever

25-y/o woman presents with malodorous vaginal discharge; W/U: visualization of the discharge under the microscope demonstrates multiple vaginal epithelial cells covered in bacteria.

Bacterial vaginosis due to Gardenella vaginalis

73-y/o presents with a painful, unilateral, vesicular rash in the distribution of the CN V_1; cornea shows diminished sensation and stains with fluorescein.

Herpes zoster ophthalmicus

29-y/o missionary with h/o travel to rural India presents with high fever and right upper quadrant (RUQ) pain; PE: severe hepatomegaly and dullness over right lower lung; abdominal CT: large, cavitating lesion in liver.

Amebic liver abscess

25-y/o sexually active man presents with dysuria, irritation, and cloudy discharge; W/U: a Gram stain of the discharge reveals neutrophils, but no organisms are visualized.

Nongonococcal urethritis, most likely due to Chlamydia trachomatis

31-y/o obese woman presents with pruritis in her skin fold beneath her pannus; PE: whitish curd-like concretions beneath the abdominal panniculus; W/U shows budding yeast on 10% KOH preparation.

Cutaneous candidiasis

NEUROSCIENCE

55-y/o man presents with lower extremity weakness and muscle atrophy; PE: positive Babinski reflex, upper extremity hyperreflexia, and spasticity.

Amyotrophic lateral sclerosis (ALS)

65-y/o presents with a gradual decline in memory and inability to complete activities of daily living; W/U: CT shows marked enlargement of ventricles and diffuse cortical atrophy.

Alzheimer disease

65-y/o woman with h/o spinal metastases from breast cancer presents with pain radiating down the back of her leg, saddle anesthesia, urinary retention; PE: absent ankle jerk reflexes; W/U: CT shows large bony fragment in lumbar spinal canal.

Cauda equina syndrome

65-y/o man with h/o carotid atherosclerosis presents with aphasia and right-sided weakness; PE: dense right-hemiparesis, positive Babinski on right; W/U: CT shows left middle cerebral artery (MCA) territory infarction and edema.

Left MCA cerebrovascular accident

20-y/o presents with nausea, vomiting, and headache 2 hours after being hit in the temple with a baseball; patient lost consciousness initially but recovered quickly; W/U: CT shows lens-shaped, right-sided hyperdense mass adjacent to temporal bone.

Epidural hematoma

40-y/o with h/o Campylobacter enteritis 1 week ago presents with ascending symmetric muscle weakness; CSF shows ↑ protein, normal cellularity (albuminocytologic dissociation).

Guillain-Barré syndrome

37-y/o man with family history (FH) of a father who died at 45 with worsening tremor and dementia presents with poor memory, depression, choreiform movements, and hypotonia; W/U: MRI demonstrates marked atrophy of the caudate nucleus.

Huntington disease

25-y/o with h/o bilateral temporal lobe contusions 1 week ago presents with a sudden increase in appetite, sexual desire, and hyperorality.

Klüver-Bucy syndrome

30-y/o woman with insidious onset of diplopia, scanning speech, paresthesias, and numbness of right upper extremity and urinary incontinence; W/U: MRI shows discrete areas of periventricular demyelination and CSF analysis is positive for oligoclonal bands.

Multiple sclerosis

65-y/o woman with h/o neurofibromatosis type 2 presents with headache, right-sided leg jerking, and worsening mental status; PE: papilledema and right-sided pronator drift; W/U: CT scan shows dural-based, enhancing, left-sided softball-sized tumor.

Meningioma

55-y/o with a h/o squamous cell carcinoma of the lung presents with nausea, vomiting, headache, and diplopia; PE: papilledema, left oculomotor palsy, right pronator drift; MRI: multiple round, hyperintense cortical and cerebellar lesions.

Metastases to brain

30-y/o woman presents with unilateral throbbing headache, nausea, photophobia, scotoma; similar symptoms occur monthly at the same time of her menstrual cycle.

Migraine

65-y/o with urinary incontinence, loss of short-term memory, and dementia; PE: wide based, magnetic gate; W/U: CT scan shows massively dilated ventricular system.

Normal pressure hydrocephalus

60-y/o presents with gradual onset of pill-rolling tremor; PE: masked facies, stooped posture, festinating gait, cogwheel muscle rigidity.

Parkinson disease

30-y/o presents with loss of libido, galactorrhea, and irregular menses; PE: bitemporal hemianopia; W/U: negative beta human chorionic gonadotropin (β-hCG).

Prolactinoma (prolactin-secreting pituitary adenoma)

45-y/o presents with the gradual onset of sharp pain radiating from his buttocks down his leg that began 2 weeks ago when he began to lift a heavy box; PE: positive straight leg raise test.

Sciatica from acute herniation of a lumbar disc

50-y/o with h/o polycystic kidney disease presents with “worst headache of life,” photophobia, nausea; PE: right eye deviated down and out; W/U: CSF is xanthrochromic.

Subarachnoid hemorrhage from ruptured berry aneurysm

32-y/o man with h/o Arnold-Chiari malformation presents with bilateral upper extremity muscle weakness; PE: loss of pain and temperature sensation, ↓ DTR in upper extremities and scoliosis; MRI shows central cavitation of the thoracic spinal cord.

Syringomyelia

75-y/o alcoholic man on warfarin for h/o atrial fibrillation presents with declining mental status, headache, and papilledema; CT shows crescenteric, hypodense, 2 cm fluid collection along convexity.

Chronic subdural hematoma

36-y/o woman with family h/o renal cell carcinoma presents with gait disturbance and blurred vision; PE: retinal hemangiomas, nystagmus, cerebellar ataxia, dysdiadokinesia; MRI shows two cerebellar cystic lesions.

von Hippel-Lindau disease

A 50-y/o with h/o alcoholism presents with psychosis, opthalmoplegia, and ataxia; MRI: mamillary body atrophy and diffuse cortical atrophy.

Wernicke encephalopathy

CARDIOVASCULAR

56-y/o woman presents with dyspnea on exertion (DOE); PE: loud S_1, delayed P_2, and a diastolic rumble; W/U: transesophageal echocardiogram shows mobile, pedunculated left atrial mass.

Atrial myxoma

60-y/o presents with chest pain relieved by sitting up and leaning forward; PE: pericardial friction rub; ECG: diffuse ST segment elevation; echocardiogram: pericardial effusion with thickening of the pericardium.

Acute pericarditis

65-y/o man presents with 1-week h/o fever, DOE, and orthopnea; PE: new, blowing holosystolic murmur at apex radiating into left axilla; W/U: blood cultures show Viridans spp. streptococci; echocardiogram: oscillating mass attached to mitral valve.

Acute infective endocarditis

60-y/o presents with dyspnea and palpitations; PE: 20 mm Hg decline in systolic BP with inspiration (pulsus paradoxus), ↓ BP, jugular venous distention, diminished S_1 and S_2; echocardiogram: large pericardial effusion.

Tamponade

58-y/o man with Marfan syndrome presents with the abrupt onset of “tearing” chest pain radiating to the back; PE: ↓ BP, asymmetric pulses, declining mental status; CXR: widened mediastinum.

Aortic dissection

70-y/o diabetic with hypercholesterolemia presents with angina, syncope, DOE, and orthopnea; PE: diminished, slowly rising carotid pulses, crescendo-decrescendo systolic murmur at second interspace at the right upper sternal border.

Aortic stenosis

80-y/o diabetic with HTN and a h/o rheumatic heart disease presents with left-sided weakness; PE: pulses are irregularly irregular; ECG: absence of P waves and irregularly irregular QRS complexes.

Atrial fibrillation (leading to embolic stroke)

70-y/o with h/o coronary artery disease (CAD) presents with worsening DOE, orthopnea, and paroxysmal nocturnal dyspnea; PE: jugular venous distention, S_3 gallop, positive hepatojugular reflex, bibasilar rales, and peripheral edema; CXR: cardiomegaly, bilateral pleural effusions.

Congestive heart failure (CHF)

50-y/o alcoholic presents with worsening DOE, orthopnea, and paroxysmal nocturnal dyspnea; PE: laterally displaced apical impulse; ECG: four-chamber dilation, mitral and tricuspid regurgitation.

Alcoholic dilated cardiomyopathy

35-y/o man with FH of sudden cardiac death presents with DOE and syncope; PE: double apical impulse, S_4 gallop, holosystolic murmur at apex and axilla; ECG: left ventricular hypertrophy and mitral regurgitation.

Hypertrophic cardiomyopathy

40-y/o black man with a h/o HTN presents with chest pain, dyspnea, and severe headache; PE: BP = 210/130 mm Hg in all four extremities, flame-shaped retinal hemorrhages, papilledema; W/U: negative vanillylmandelic acid (VMA), urine catecholamines, and cardiac enzymes.

Malignant hypertension

35-y/o woman with a h/o rheumatic fever presents with worsening DOE and orthopnea; PE: loud S_1, opening snap and low-pitched diastolic murmur at the apex; CXR: left atrial enlargement.

Mitral stenosis

65-y/o man presents with substernal pressure for the past hour with radiation of the pain into the jaw and left arm, nausea, diaphoresis, and dyspnea; PE: S_4 gallop; W/U: ↑ serum troponin and CK-MB; ECG: ST segment elevation in leads aVL, V_1 to V_6.

Anterior myocardial infarction

PULMONARY

7-y/o with h/o environmental allergies presents in acute respiratory distress; PE: tachypnea, expiratory wheezes, intercostal retractions, accessory muscle usage during respiration; CXR: hyperinflation; CBC: eosinophilia.

Bronchial asthma

60-y/o with a 50 pack-year h/o smoking presents with fever and cough productive of thick sputum for the past 4 months; PE: cyanosis, crackles, wheezes; W/U: Hct = 48, WBC = 12,000; CXR: no infiltrates.

Chronic bronchitis

60-y/o with a 50 pack-year h/o smoking presents with DOE and dry cough, but no chest pain; PE: ↓ breath sounds, ↑ heart rate (HR), hyperresonant chest, distant S_1 and S_2; CXR: hyperlucent lung fields.

Emphysema

60-y/o with 50 pack-year h/o smoking presents with fatigue, DOE, hoarseness, anorexia; PE: miosis, ptosis, anhydrosis, dullness to percussion at right apex; CXR: large, hilar mass extending into the right superior pulmonary sulcus.

Pancoast tumor (most likely bronchogenic squamous cell carcinoma, causing Horner syndrome)

60-y/o 4 days s/p total knee replacement has a sudden onset of tachycardia, tachypnea, sharp chest pain, hypotension; W/U: arterial blood gas (ABG) shows respiratory alkalosis; ECG: sinus tachycardia; lower extremity venous duplex ultrasound (U/S): clot in right femoral vein.

Pulmonary embolism (most likely from DVT)

30-y/o black woman presents with DOE, fever, arthralgia; PE: iritis, erythema nodosum; W/U: eosinophilia, ↑ serum ACE levels; PFT: restrictive pattern; CXR: bilateral hilar lymphadenopathy, interstitial infiltrates; lymph node biopsy: noncaseating granulomas.

Sarcordosis

40-y/o white man presents with chronic rhinosinusitis, ear pain, cough, dyspnea; PE: ulcerations of nasal mucosa, perforation of nasal septum; W/U: ↑ C-ANCA; U/A: red cell casts; biopsy of nasal lesions: necrotizing vasculitis and granulomas.

Wegener granulomatosis

GASTROENTEROLOGY

20-y/o woman presents with bloody diarrhea and joint pain; PE: abdominal tenderness, guaiac ⊕ stool; laboratory values: ↑ ESR and CRP, HLA-B27 +; colonoscopy: granular, friable muscosa with pseudopolyps throughout the colon.

Ulcerative colitis (UC)

28-y/o patient with h/o of UC presents with severe abdominal pain, distention, and high fever; PE: severe abdominal tenderness; CBC: leukocytosis; abdominal x-ray (AXR): dilated (> 6 cm) transverse colon.

Toxic megacolon

cirrhotic patient presents with massive hematemesis; PE: jaundice, ↓ BP, ↑ HR, ascites; W/U: stems pancytopenia, ↑ ALT and AST; EGD: actively bleeding vessel with numerous cherry red spots.

Esophageal varices

38-y/o man with recent h/o fatigue, excessive thirst, and impotence presents with hyperpigmentation of his skin; PE: cardiomegaly, HSM; W/U: ↑ glucose, ferritin, transferrin, and serum iron.

Hemochromatosis (hereditary)

19-y/o woman with recent h/o behavioral disturbance presents with jaundice and resting tremor; PE: pigmented granules in cornea and HSM; W/U: ↓ serum ceruloplasmin.

Wilson disease

29-y/o with h/o intermittent jaundice since receiving blood transfusion after motor vehicle accident (MVA) 2 years ago; PE: RUQ tenderness, hepatomegaly; W/U: negative HBV serology.

Hepatitis C infection

31-y/o woman presents with 10-month h/o foul-smelling, greasy diarrhea; PE: pallor, hyperkeratosis, multiple ecchymoses, and abdominal distention; W/U: abnormal D-xylose test.

Celiac disease

60-y/o white man presents with steatorrhea, weight loss, arthritis, and fever; small bowel biopsy shows PAS ⊕ macrophages and gram-positive bacilli.

Whipple disease

19-y/o Jewish woman with h/o chronic abdominal pain presents with recurrent UTIs and pneumaturia; PE: diffuse abdominal pain; CT: enterovesical fistula; colonoscopy: skip lesions of linear ulcers and transverse fissures giving cobblestone appearance to mucosa.

Crohn’s disease

21-y/o man presents with hematemesis after ingestion of aspirin and seven shots of whiskey; PE: diaphoretic, ↑ HR, epigastric tenderness; EGD: edematous, friable, reddened gastric mucosa.

Acute gastritis

patient with h/o peptic ulcer disease (PUD) presents with melena; PE: ↑ HR, diaphoretic, diffuse abdominal pain; W/U: nasogastric tube (NGT) aspirate is bloody; EGD: visible bleeding vessel distal to the pylorus.

Bleeding duodenal ulcer

40-y/o obese, mother of four children presents with constant RUQ pain radiating to right scapula, N/V; PE: fever, tenderness, and respiratory pause induced by RUQ palpation, painful palpable gallbladder; W/U: ↑ WBC, ↑ ALP; U/S: thickened gallbladder wall, pericholecystic fluid with gallstones present.

Acute cholecystitis

39-y/o man presents with dull, steady epigastric pain radiating to the back after an alcohol binge, N/V; PE: fever, ↑ BP, epigastric tenderness, guarding, and distention; W/U: ↑↑ amylase/lipase, ↑ WBC; AXR: ⊕ sentinel loop and colon cutoff sign.

Acute pancreatitis

65-y/o black man with h/o smoking presents with anorexia, weight loss, pruritis, and painless jaundice; PE: palpable, nontender, distended gallbladder, migratory thrombophlebitis; W/U: ↑ direct BR, ALP, carcinoembryonic antigen (CEA), and CA 19-9.

Pancreatic adenocarcinoma

60-y/o black man with h/o gastroesophageal reflux disease (GERD) presents with weight loss and dysphagia; EGD: partially obstructing mass near GE junction.

Esophageal carcinoma

65-y/o presents with severe worsening left lower quadrant (LLQ) pain, N/V, and diarrhea; PE: fever, LLQ tenderness, local guarding, and rebound tenderness; W/U: ↑ WBC; abdominal CT: edematous colonic wall with localized fluid collection.

Diverticulitis

30-y/o woman presents with periumbilical pain which has now migrated to the RLQ followed by anorexia, N/V; PE: low-grade fever, local RLQ guarding, rebound tenderness, RLQ tenderness on LLQ palpation; W/U: β-hCG negative, ↑ WBC with left shift.

Appendicitis

55-y/o presents with colicky abdominal pain, small-caliber stools, and occasional melena; PE: cachexia, abdominal discomfort, guaiac ⊕ colonoscopy shows obstructing mass seen in ascending colon.

Right-sided colon carcinoma

80-y/o woman presents with halitosis, dysphagia, and regurgitation of undigested foods; W/U: barium swallow shows posterior midline pouch greater than 2 cm in diameter arising just above the cricopharyngeus muscle.

Zenker diverticulum

55-y/o Asian woman with h/o HBV presents with dull RUQ pain; PE: weight loss, painful hepatomegaly, ascites, jaundice; W/U: ↑ ALT/AST, ↑ α-fetoprotein; abdominal CT: mass seen in right lobe of liver.

Hepatocellular carcinoma

55-y/o with h/o choledocholithiasis presents with fever, chills, and RUQ pain; PE: jaundice; W/U: ↑ WBC, BR, and ALP; U/S: stone in common bile duct.

Cholangitis

43-y/o man presents with epigastric pain, diarrhea, and recurrent peptic ulcers; PE: epigastric tenderness; W/U: ↑ fasting gastrin levels, paradoxic ↑ in gastrin with secretin challenge; Octreotide scan: detects lesion in pancreas.

Zollinger-Ellison syndrome

72-y/o presents with recurrent, low-grade, painless hematochezia; PE: guaiac ⊕ stool; colonoscopy reveals slightly raised, discrete, scalloped lesion with visible draining vein in right colon.

Angiodysplasia

63-y/o Japanese man with h/o atrophic gastritis presents with weight loss, indigestion, epigastric pain, and vomiting; PE: supraclavicular lymph node; W/U: anemia, ⊕ fecal occult blood.

Gastric carcinoma

48-y/o with chronic watery diarrhea, hot flashes, and facial redness; PE: shows II/VI right-sided ejection murmur; W/U: ↑ 5-hydrocyindoleacetic acid (5-HIAA) in urine.

Carcinoid syndrome

40-y/o presents with dysphagia, regurgitation, and weight loss; W/U: barium swallow demonstrates dilated esophagus with distal narrowing (bird beak appearance).

Achalasia

16-y/o with strong FH of colorectal CA presents with rectal bleeding and abdominal pain; W/U: anemia; flexible sigmoidoscopy: > 100 adenomatous polyps visualized.

Familial adenomatous polyposis (FAP)

34-y/o bulimic presents with sudden-onset retrosternal pain after vigorous vomiting; upper GI series shows extravasation of contrast into mediastinum.

Boerhaave syndrome

44-y/o heavy smoker presents with heartburn and regurgitation that is worse when lying down and is relieved with antacids; upper GI series reveals mild hiatal hernia.

GERD

5-day-old infant presents with abdominal distention and failure to pass meconium until after a rectal examination; XR shows massively dilated colon.

Hirschsprung disease

39-y/o woman with h/o rheumatoid arthritis presents with fatigue and pruritus; PE: jaundice and HSM; W/U reveals ↑↑ ALP and γ-glutamyl transpeptidase (GGT) and presence of antimitochondrial antibodies.

Primary biliary cirrhosis

2-week-old first-born male infant presents with projectile vomiting and dehydration; PE: visible peristalsis and palpable knot in epigastrum.

Hypertrophic pyloric stenosis

50-y/o with long h/o retrosternal pain drinks and smokes despite undergoing treatment for GERD; biopsy of distal esophagus shows metaplasia.

Barrett s esophagus

34-y/o woman with factor V Leiden deficiency presents with abdominal distention and jaundice; PE: pitting pedal edema, markedly visible leg veins, HSM, and absent hepatojugular reflex; U/S shows obstruction of hepatic veins.

Budd-Chiari syndrome

7-month-old infant presents with vomiting and currant jelly-appearing stools; PE: right-sided, sausage-shaped, palpable mass in abdomen; barium enema (BE) shows telescoping of intestines.

Intussusception

REPRODUCTIVE/ENDOCRINE

31-y/o presents with loss of libido, galactorrhea, and irregular menses; PE: bitemporal hemianopia; W/U: negative β-hCG.

Prolactinoma

7-month-old with history of multiple infections turns cyanotic when aggravated; PE: abnormal facies, cleft palate, heart murmur; W/U: hypocalcemia, tetrology of Fallot.

DiGeorge syndrome (22qll)

Patient presents to clinic with polyuria and polydipsia; W/U: urine specific gravity 1.005, urine osmolality 200 mOsm/kg, hypernatremia.

Diabetes insipidus

30-y/o white woman presents with weight loss, tremor, and palpitations; PE: brisk DTRs, ophthalmopathy, pretibial myxedema; W/U: ↓ TSH, ↑ T_4, ↑ T_3 index.

Graves disease

40-y/o woman presents with fatigue, constipation, and weight loss; PE: puffy face, cold dry hands, coarse hair, and enlargement of thyroid gland; W/U: ↑ TSH, ↓ T_3 and T_4, ⊕ antimicrosomal and antithyroglobulin AB.

Hashimoto disease

32-y/o woman with h/o recurrent PUD presents with episodes of hypocalcemia and nephrolithiasis; W/U: fasting hypoglycemia, ↑ gastrin levels, and hypercalcemia.

Multiple endocrine neoplasia (MEN) 1

70-y/o presents with episodal hypertension, nephrolithiasis, and diarrhea; PE: ↑ BP, thyroid nodule; W/U: ↑ calcitonin levels, ↑ urinary catecholamines.

MEN 2

Female patient presents with bone pain, kidney stones, depression, and recurrent ulcers; W/U: hypercalcemia, hypophosphatemia, and hypercalciuria.

Hyperparathyroidism

35-y/o woman presents with weightgain, irregular menses, and HTN; PE: ↑ BP, ↑ weight in face and upper back, hirtuism, multiple ecchymoses; W/U: ↑ ACTH levels and suppression with high-dose dexamethasone suppression test.

Cushing disease

50-y/o woman presents with HTN, muscle weakness, and fatigue; W/U: hypokalemia, hypernatremia, and metabolic alkalosis.

Conn syndrome

30-y/o woman presents with progressive weakness, weight loss, N/V; PE: hyperpigmentation of skin, ↓ BP; W/U: hyperkalemia, hyponatremia, and eosinophilia.

Addison disease

40-y/o presents with episodes of HA, diaphoresis, palpitations, and tremor; PE: ↑ BP, ↑ HR; W/U: ↑ in urinary VMA and homovanillic acid.

Pheochromocytoma

17-y/o white adolescent with h/o diabetes mellitus (DM) presents with diffuse abdominal pain, N/V, and slight confusion; PE: ↓ BP, shallow, rapid breathing pattern; W/U: glucose = 300, hypokalemia, hypophosphatemia, and metabolic acidosis.

Diabetic ketoacidosis (DKA)-DM type 1

60-y/o diabetic obese patient found at home confused and disoriented; PE: ↓ BP, ↑ HR; W/U: glucose > 1000.

Hyperosmolar hyperglycemic non-ketotic (HHNK)-DM type 2

50-y/o woman presents with h/o weakness, blurred vision, and confusion several hours after meals, which improves with eating; W/U: ↑ fasting levels of insulin and hypoglycemia.

Insulinoma (with Whipple triad)

Newborn presents with ambiguous genitalia; PE: lethargy and ↓ BP; W/U:↓ Na+, ↑ K+, ↓ 17 α-OH-progesterone, ↑ ACTH, and karyotype of 46, XX.

Congenital adrenal hyperplasia (21α-hydroxylase deficiency)

7-y/o girl presents with breast buds andmonthly vaginal bleeding; PE: height and weight >> 95 percentile, full pubic and axillary hair; hand x-ray shows advanced bone age.

Precocious puberty

21-y/o woman presents with no h/o menarche; PE: normal breast tissue, no axillary or pubic hair, vagina ending in blind pouch, no palpable cervix or uterus; karyotype shows 46, XY.

Androgen insensitivity (testicular feminization) syndrome

45-y/o with recent h/o coarsening of facial features presents with headaches and states that his shoes no longer fit; PE: enlarged jaw, tongue, hands, and feet, and bitemporal hemianopia.

Acromegaly

65-y/o smoker with h/o lung cancer presents with fatigue and oliguria; W/U: ↓ Na+, ↓ serum osmolarity, ↑↑ urine osmolarity.

Syndrome of inappropriate antidiuretic hormone (SIADH)

22-y/o sexually active woman presents with dysuria, dyspareunia, vulvar pain for the past 3 days. PE: soft ulcer on labia majora, inguinal lymphadenopathy; W/U: culture grows Haemophilus ducreyi.

Chancroid

20-y/o sexually active woman presents with crampy abdominal pain and purulent vaginal discharge; PE: fever and adnexal tenderness; W/U: ↑ WBCs, ↑ ESR, and combined infection with C. trachomatis and Neisseria gonorrhoeae.

Pelvic inflammatory disease (PID)

18-y/o woman with 3 days of vaginal pruritis; PE: thick, white discharge; W/U: budding yeast on KOH preparation.

Vaginal candidiasis

28-y/o woman postpartum day 1 with excessive hemorrhage in labor becomes weak and loses consciousness. PE: hypotension; W/U: ↓ cortisol, ↓ TSH, ↓ fT_4, ↓ LH, ↓ FSH.

Sheehan syndrome (pituitary apoplexy)

31-y/o woman with h/o PID presents with sudden-onset nausea and LLQ pain; PE: ↓ BP, ↑ HR, rebound tenderness in LLQ; W/U shows ⊕ β-hCG and fluid in cul-de-sac on U/S.

Ruptured ectopic pregnancy

28-y/o man presents with gynecomastia and painless lump in his left testicle for 3 months; PE: firm 4 cm mass on left testis; W/U: ↑↑ serum hCG and AFP.

Testicular carcinoma

35-y/o man with sensation of heaviness in left scrotum; appears like a “bag of worms” on examination.

Varicocele

62-y/o obese nun with h/o menopause at age 57 presents with vaginal bleeding for the past 4 months; PE shows normal-sized uterus; Pap smear reveals abnormal endometrial cells.

Endometrial carcinoma

52-y/o obese patient presents with numbness in hands and feet; PE: ↑ BP and retinopathy; W/U: ↑ HbA1c and glycosuria.

DM type 2

55-y/o woman presents with an itching, scaling, oozing rash over her left nipple; PE: serosanguinous discharge and eczematous redness of left nipple with axillary lymphadenopathy.

Paget disease of the breast

4-y/o girl presents with a “bunch of grapes” protruding from her vagina. W/U: desmin positive.

Sarcoma botryoides

37-y/o woman presents with dysmenorrhea, dyspareunia, menorrhagia, and pain coinciding with her menstrual cycle; PE: nodularity of uterosacral ligaments and cul-de-sac.

Endometriosis

22-y/o woman with 6-month h/o amenorrhea presents for infertility evaluation; PE: obesity, hirsutism; W/U: ↑ LH:FSH ratio, ↑ testosterone, and enlarged ovaries on U/S.

Polycystic ovarian syndrome (Stein-Leventhal syndrome)

44-y/o with recent h/o thyroidectomy presents with muscle cramping; PE: circumoral numbness, positive Trousseau and Chvostek signs.

Hypoparathyroidism

23-y/o woman marathon runner presents with lack of menses for 5 months; PE shows no signs of pregnancy; W/U: negative β-hCG, normal prolactin and thyroid hormones.

Secondary amenorrhea

28-y/o black woman at 35 weeks gestation in her first pregnancy presents with swollen legs; PE: ↑ BP and pitting pedal edema; W/U: 3+ proteinuria.

Preeclampsia

2-y/o child presents with developmental delay; PE: macroglossia, short stature, and protuberant abdomen; W/U: ↑ TSH, ↓ T_3 and T_4.

Congenital hypothyroidism (cretinism)

51-y/o woman with 9-month h/o amenorrhea presents with fatigue and flushing of skin; PE: atrophic vaginal mucosa; W/U: ↑ FSH and LH.

Menopause

24-y/o woman presents with painless lump in her left breast; PE: small, firm, palpable, and freely mobile, rubbery mass in the upper-outer quadrant of the breast.

Fibroadenoma

19-y/o man is brought to you for failure of pubertal maturation; PE: anosmia, ↓ muscle mass, no axillary or pubic hair, and hypogonadism; W/U: ↓ LH and FSH.

Kallmann syndrome

9-y/o girl presents with muscle cramps; PE: rounded face with flat nasal bridge, abnormal dentition, positive Trousseau and Chvostek sign, and shortened third and fourth metacarpals.

Albright hereditary osteodystrophy (pseudohypoparathyroidism)

22-y/o pregnant woman at 27 weeks with painless vaginal bleeding that stopped after an hour. W/U: placenta overlying the cervical os on ultrasound.

Placenta previa

19-y/o woman with h/o recent hydatidiform mole presents with vaginal bleeding, nausea, and vomiting; PE: vascular growth at cervical os and enlarged uterus; W/U: ↑↑ β-hCG.

Choriocarcinoma

35-y/o man presents for sterility evaluation; PE: eunuchoid body habitus, small testicles, and gynecomastia; karyotype reveals 47, XXY.

Klinefelter syndrome

RENAL AND GENITOURINARY

Patient hospitalized for CHF is started on an aminoglycoside for a UTI and develops oliguria, N/V, and malaise; PE: ↑ BP and asterixis; serum electrolytes: ↑ creatinine (Cr), K+; UA: “muddy brown” casts, FeNa+ > 3%.

Acute renal failure (drug-induced ATN)

70-y/o black man with h/o of life-long DM presents with peripheral edema, SOB, and oliguria; PE: auscultatory rales, pitting edema, myoclonus, and uremic frost; serum electrolytes: ↑ Cr, hyperkalemia, hypocalcemia, hyperphosphatemia.

Chronic renal failure

Teenage female presents with fever, chills, and flank pain; PE: costovertebral angle (CVA) tenderness; UA: leukocyte esterase ⊕, 30 WBC/hpf with WBC casts.

Pyelonephritis

32-y/o man presents with pain and hematuria; PE: ↑ BP, palpable kidney, and midsystolic ejection click; abdominal U/S: multiple cysts of renal parenchyma; cerebral angiogram: unruptured berry aneurysm.

Adult polycystic kidney disease

20-y/o man presents with significant blood loss following a trauma and begins to have decreased urine output. W/U: oliguria, FeNa 1%, and BUN:Cr > 20.

Acute renal failure—prerenal

12-y/o girl with recent h/o sore throat presents with low urine output and dark urine; PE: periorbital edema; W/U: hematuria, ↑ BUN and Cr, ↑ antistreptolysin O (ASO) titer.

Poststreptococcal glomerulonephritis

45-y/o Asian man with h/o hepatitis B presents with malaise, edema, and foamy urine; PE: anasarca; W/U: proteinuria (> 3.5 g/day), hyperlipiduria; hyperlipidemia and hypoalbuminemia.

Membranous glomerulonephritis

Male infant is born with flattened facies, joint position abnormalities, and hypoplastic lungs. Oligohydramnios was noted prior to delivery.

Potter sequence—secondary to renal agenesis

80-y/o man presents with urinary hesitancy, nocturia, and weak urinary stream; PE: diffusely enlarged rubbery prostate; serum electrolytes: ↑ Cr, UA is WNL.

Benign prostatic hyperplasia (BPH)

68-y/o man, who is a smoker, presents with flank pain and hematuria; PE: fever, palpable kidney mass; W/U: hypercalcemia, polycythemia.

Renal cell carcinoma

20 y/o man presents with acute onset of left testicular pain and N/V; PE: swollen, tender testicle in transverse position, absent cremasteric reflex on left side; Doppler: no flow detected in left testicle.

Testicular torsion

65-y/o man, who is a smoker, presents with painless hematuria and occasional urinary urgency and frequency; PE: unremarkable; urine cytology positive for malignant cells.

Bladder—urothelial carcinoma

85-y/o man presents with back pain, weight loss, and weak urinary stream; PE: palpable firm nodule on digital rectal examination (DRE); W/U: ↑ PSA.

Prostate cancer

25-y/o Asian man presents with N/V and colicky right flank pain; PE: acute distress and CVA tenderness; W/U: hematuria and discrete radiopacities on abdominal XR.

Renal stones

45-y/o with documented h/o aortic atheromatous plaques presents with recent-onset, severe left flank pain, and hematuria; abdominal CT: wedge-shaped lesion in the left kidney.

Renal infarct

3-y/o boy presents with h/o flank mass found recently by his mother while bathing him; PE: palpable mass in left flank; abdominal CT: large mass growing out of left kidney.

Wilms tumor

55-y/o with long h/o DM presents with increasing fatigue and edema; PE: ↑ BP, retinopathy, and pitting edema; W/U: severe proteinuria and glycosuria.

Diabetic nephropathy (glomerulosclerosis)

21-y/o sexually active woman presents with frequency and dysuria; PE: suprapubic tenderness; W/U: E. coli-positive urine cultures.

Urinary tract infection (UTI)

25-y/o man presents with hemoptysis, dark urine, and fatigue; PE: bilateral crackles at lung bases; W/U: oliguria, hematuria, and anti-GBM antibodies.

Goodpasture syndrome

7-y/o presents in stupor after ingesting antifreeze; PE: Kussmaul respirations and mental status changes; W/U reveals anion gap of 21 mEq/L.

Metabolic acidosis (ethylene glycol toxicity)

6-y/o boy presents with hematuria and worsening vision; PE: corneal abnormalities, retinopathy, sensorineural hearing loss; W/U: hematuria with dysmorphic red cells.

Alport syndrome

3-y/o boy with h/o recent URI presents with facial edema; PE: ascitic fluid in abdomen and pedal edema; W/U reveals 4+ proteinuria and ↓ serum albumin.

Minimal change disease

HEMATOLOGY/ONCOLOGY

50-y/o with h/o bone marrow transplant for chronic myelogenous leukemia (CML) 3 weeks ago presents with severe pruritis, diarrhea, and jaundice; PE: violaceous rash on palms and soles; W/U: ↑ BR, ALT, and AST.

Graft-versus-host disease

1-y/o Greek child presents with pallor and delayed milestones; PE: skeletal abnormalities, splenomegaly; peripheral blood smear (PBS): hypochromic microcytic RBCs, target cells, fragmented RBCs; skull XR: “hair-on-end” appearance.

β-Thalassemia

10-y/o with a h/o recurrent chest pain presents with fever and bilateral leg pain; PE: febrile, multiple leg ulcers; PBS shows sickle-shaped erythrocytes; Hb electrophoresis shows HbS band.

Sickle cell anemia

60-y/o with headache, vertigo, blurry vision, pruritus, joint pain; PE: ↑ BP, plethoric splenomegaly; W/U: Hct = 60, mild leukocytosis, and hyperuricemia.

Polycythemia vera

4-y/o boy with a 1-week h/o fever, pallor, headache, and bone tenderness; PE: fever, HSM, and generalized, nontender lymphadenopathy; PBS reveals absolute lymphocytosis with abundant TdT+ lymphoblasts.

Acute lymphoblastic leukemia

27-y/o presents with 2-month h/o fatigue, oropharyngeal candidiasis, pseudomonal UTI, and epistaxis; PE: numerous petechiae and ecchymoses of skin, gingival mucosal bleeding, guaiac ⊕ stools; W/U: ↑ WBC; PBS shows >30% myeloblasts with Auer rods.

Acute myelocytic leukemia

17-y/o man presents with a 2-month h/o fever, night sweats, and weight loss; PE: nontender, cervical lymphadenopathy, and HSM; CBC: leukocytosis; CXR: bilateral hilar adenopathy; lymph node biopsy: Reed-Sternberg cells.

Hodgkin disease

60-y/o man presents with fatigue and anorexia; PE: generalized lymphadenopathy and HSM; W/U: WBC = 250,000, positive direct Coombs test; PBS: small, round lymphocytes predominate with occasional smudge cells.

Chronic lymphocytic leukemia

10-y/o African child presents with a 3-week h/o a rapidly enlarging, painless mandibular mass; CBC: mild anemia and leukopenia; cytogenetics reveal a t(8:14) translocation; excisional biopsy: “starry-sky” pattern.

Burkitt lymphoma

35-y/o presents with a 3-year h/o mild weight loss, anorexia, worsening DOE; PE: splenomegaly; CBC: mild anemia, WBC = 125,000; PBS: granulocytosis with 10% myeloblasts; cytogenetics reveal a t(9:22) translocation.

Chronic myelocytic leukemia

55-y/o with a recent h/o streptococcal pneumonia presents with bone pain and weight loss; W/U: mild anemia, hypercalcemia; PBS: roleau formation; UA: Bence-Jones proteinuria; serum electrophoresis: M spike; XR: cranial “punched-out” lesions.

Multiple myeloma

18-y/o woman develops dyspnea and declining mental status 1 hour after a C-section complicated by excess blood loss; PE: mucosal bleeding, large clot in the vaginal vault; W/U: ↑ D-dimer, ↑ PT/PTT, ↓ antithrombin III, and thrombocytopenia.

Disseminated intravascular coagulation

7-y/o with h/o viral URI 1 week ago presents with epistaxis; PE: petechial hemorrhages of nasal mucosa and extremities; W/U: ↓ platelets, normal PT and PTT; bone marrow biopsy: ↑↑ megakaryocytes.

Idiopathic thrombocytopenic purpura

8-y/o with a h/o vomiting and diarrhea after eating a hamburger last week presents with fatigue, periorbital edema, and oliguria; PE: purpuric rash; CBC: ↓ platelets; PBS: burr cells, helmet cells; UA: RBC casts, proteinuria, hematuria.

Hemolytic uremic syndrome

8-y/o with a h/o environmental allergies presents with a painful rash on the legs, abdominal discomfort, joint pain; UA: hematuria and RBC casts; renal biopsy: glomerular mesangial IgA deposits.

Henoch-Schonlein purpura

8-y/o boy presents with a swollen painful knee; FH: maternal grandfather died from hemorrhage after a cholecystectomy; PE: cutaneous ecchymoses; W/U: gross blood in swollen knee joint, ↑ PTT, normal PT and platelet count, ↑ bleeding time.

Hemophilia A

2-y/o boy with a h/o recurrent epistaxis presents with the third episode of otitis media in 4 months; PE: eczematous dermatitis; W/U: thrombocytopenia, ↓ IgM, ↑ IgA.

Wiskott-Aldrich syndrome

Newborn develops jaundice rapidly during the first day of life; PE: HSM; W/U: severe anemia, ⊕ indirect Coombs test in both mother and newborn.

Rh incompatibility

16-y/o adolescent with a h/o menorrhagia presents with fatigue; PE: multiple cutaneous bruises; guiaic ⊕ stools; W/U: ↑ bleeding time, ↓ factor VIII, normal platelet count, PT, and PTT.

von Willebrand disease

SKIN AND CONNECTIVE TISSUES

30-y/o man with h/o recurrent sinusitis presents for sterility evaluation; PE: heart sounds are best heard over right side of chest.

Kartagener syndrome

9-y/o with h/o easy bruising and hyperextensible joints presents to the ER after dislocating his shoulder for the fifth time this year.

Ehlers-Danlos syndrome

5-y/o presents to the ER with his sixth bone fracture in the past 2 years; PE: bluish sclera and mild kyphosis; XR: fractures with evidence of osteopenia.

Osteogenesis imperfecta

8-y/o with a long h/o severe sunburns and photophobia presents to the dermatologist for evaluation of several lesions on the face that have recently changed color and size.

Xeroderma pigmentosum

6-y/o boy presents to the ophthalmology clinic with sudden ↓ visual acuity; PE: unusual body habitus, long and slender fingers, pectus excavatum, and superiorly dislocated lens.

Marfan syndrome

36-y/o with h/o celiac disease presents with clusters of erythematous vesicular lesions over the extensor surfaces of the extremities.

Dermatitis herpetiformis

5-y/o patient presents with honey-colored crusted lesions at the angle of his mouth; Gram stain of pus: gram-positive cocci in chains.

Impetigo

29-y/o HIV-positive patient presents with multiple painless pearly-white umbilicated nodules on the trunk and anogenital area.

Molluscum contagiosum

68-y/o fair-skinned farmer presents with large, telangiectatic, and ulcerated nodule on the bridge of the nose.

Basal cell carcinoma

11-y/o presents with bilateral wrist pain and a rash; PE: erythematous, reticular skin rash of the face and trunk with a “slapped-cheek appearance.”

Erythema infectiosum

43-y/o woman presents with difficulty swallowing; PE: bluish discoloration of the hands and shiny, tight skin over her face and fingers.

Progressive systemic sclerosis (scleroderma)

5-y/o Asian boy presents with fever and diffuse rash including the palms and soles; PE: cervical lymphadenopathy, conjunctival injection, and desquamation of his fingertips; echocardiogram reveals dilation of coronary arteries.

Kawasaki syndrome (mucocutaneous lymph node syndrome)

33-y/o patient presents with itchy, purple plaques over her wrists, forearms, and inner thigh; PE: Wickham striae.

Lichen planus

25-y/o woman with h/o Raynaud phenomenon presents with arthralgias and myositis; W/U reveals esophageal hypomotility and ↑ anti-nRNP titers.

Mixed connective tissue disease

MUSCULOSKELETAL

25-y/o man presents with morning stiffness, heel pain, and photophobia; PE: ↓ lumbar spine extension and lateral flexion, tenderness on lumbar spinous processes and iliac crests; W/U: HLA-B27 ⊕; XR: bamboo spine.

Ankylosing spondylitis

7-y/o girl presents with a limp, anorexia, and spiking fevers; PE: salmon-pink linear rash on trunk and extremities and swelling of bilateral hip, knee, elbow, and wrist joints; W/U: ↑ ESR.

Juvenile rheumatoid arthritis

50-y/o woman presents with long-standing h/o morning stiffness and diffuse joint pain; PE: boutonierre and swan neck deformities of fingers, shoulder tenderness, and ↓ range of motion (ROM), symmetric and bilateral knee swelling; W/U: RF positive.

Rheumatoid arthritis

25-y/o man with a h/o urethritis 2 weeks ago presents with unilateral knee pain, stiffness, and eye pain; PE: conjunctivitis, edema, and tenderness of left knee, mucoid urethral discharge; W/U: urethral swab ⊕ for Chlamydia.

Reiter syndrome

45-y/o woman presents with dry eyes and dry mouth, PE: parotid gland enlargement, bibasilar rales; W/U: ⊕ ANA, RF, SS-A/Ro titers.

Sjögren syndrome

70-y/o woman presents with pain in hands that is worse with activity, PE: Heberden and Bouchard nodes, bony enlargement at DIP and PIP joints, bilateral knee effusions; W/U: negative RF, normal ESR; hand XR: joint space narrowing, osteophytes.

Osteoarthritis

72-y/o woman presents with a 6-week h/o morning stiffness in neck and shoulders; PE: low-grade fever, tenderness to palpation, and decreased ROM in neck, shoulder, hip joints; W/U: ↓ ESR and CRP, but negative RF.

Polymyalgia rheumatica

50-y/o man presents with acute onset of sharp pain in the left great toe; PE: severe tenderness, swelling, and warmth of the left MTP joint; synovial fluid analysis shows negatively birefringent crystals.

Gout

25-y/o woman with a 1-week h/o pain in several joints presents with swelling, redness, and pain in her right knee; PE: pustular lesions on palms, right knee shows erythema, tenderness, and ↓ ROM; W/U: gram-negative diplococci in synovial fluid.

Gonococcal arthritis

28-y/o woman presents with difficulty keeping her eyelids open and holding her head up during the day; PE: weakness of facial muscles, deltoids; W/U: anti-ACh titer +; CXR: anterior mediastinal mass.

Myasthenia gravis (associated with thymoma)

20-y/o black woman presents with fatigue, arthralgias, Raynaud phenomenon, and pleuritic chest pain; PE: butterfly malar facial rash; W/U: ↓ platelets, proteinuria, and ⊕ ANA, anti-dsDNA, and anti-Smith Abs.

Systemic lupus erythematosus (SLE)

20-y/o with a h/o developmental delay presents with facial weakness; PE: cataracts, marked weakness in muscles of hand, neck, and distal leg with sustained muscle contraction; genetic testing: CTG repeat expansion within DMPK gene.

Myotonic dystrophy

BEHAVIORAL SCIENCE

20-y/o woman presents with excessive anxiety about a variety of events for more than half of the days for the last 7 months.

Generalized anxiety disorder

8-y/o boy presents with a 5-month h/o regular bedwetting episodes; PE is unremarkable and fasting glucose is WNL.

Enuresis

28-y/o man who systematically checks each lock in his house every time before leaving, often causing him to be over an hour late for meetings.

Obsessive-compulsive disorder

29-y/o man presents with a 9-month h/o insatiable urges to rub himself against strangers, which he has regretably acted on several times.

Frotteurism

22-y/o woman college student who is 20% below her ideal body weight complains of not having any menstrual cycles and “feeling fat.”

Anorexia nervosa

26-y/o woman medical student is convinced for the past 9 months that she has SLE and despite numerous negative workups, she fears she will have to drop out of school.

Hypochondriasis

17-y/o woman presents with complaints of “feeling fat” and h/o eating dinner alone in her bedroom; PE shows normal height and weight, dental erosions, and scars on the back of her hand.

Bulimia

21-y/o woman with no h/o trauma presents to the ER because she cannot feel or move her legs; W/U is WNL; detailed history reveals that her boyfriend left her this morning.

Conversion disorder

43-y/o alcoholic with h/o confabulation and amnesia presents to ER after falling down; PE shows nystagmus and ataxic gait; W/U reveals macrocytic anemia.

Wernicke-Korsakoff syndrome

6-y/o presents with 8-month h/o hyperactivity, inattentiveness, and impulsivity both at school and at home; PE and W/U are WNL.

Attention deficit hyperactivity disorder (ADHD)

33-y/o woman presents to your office distressed after turning down a lucrative job offer because of the requirement to speak in front of people.

Social phobia

9-y/o boy with 2-year h/o involuntary tics is brought to your office because he has recently been shouting obscenities.

Tourette syndrome

33-y/o woman nurse presents with recent occurrences of hypoglycemia; PE reveals multiple crossed scars on abdomen; W/U shows insulin/C-peptide ratio > 1.0.

Factitious disorder (Munchausen syndrome)

33-y/o is referred to you for reports of random episode of shouting and screaming during the night; he has no recollection of the event and denies having nightmares.

Sleep terror disorder

16-y/o with h/o sudden-onset daytime sleep attacks with loss of muscle tone and audiovisual hallucinations while waking and falling asleep.

Narcolepsy

19-y/o with an 8-month h/o deteriorating grades and social withdrawal presents with auditory hallucinations; PE shows odd thinking patterns, tangential thoughts, and flattened effects.

Schizophrenia

24-y/o with h/o depression presents with ↓ need for sleep and auditory hallucinations; PE reveals easy distractibility and pressured speech; W/U shows normal TSH and negative toxicology screen.

Bipolar disorder—type 1 (manic episode)

48-y/o woman presents with recent h/o early morning waking, ↓ appetite, feelings of guilt, and loss of interest in her usual hobbies over the past 3 months; PE and laboratory results are WNL.

Major depressive disorder

68-y/o veteran presents with complaints of vivid flashbacks, hypervigilance, and difficulty falling asleep for the past several years; patient appears very anxious during the PE.

Posttraumatic stress disorder

6-month-old child presents with unyielding crying; PE reveals multiple bruises in different stages of healing and bilateral retinal hemorrhages; XR shows multiple, healing fractures along posterior ribs.

Shaken baby syndrome

43-y/o woman from Boston finds herself in Utah, but does not remember why she is there or how she got there; PE and W/U are WNL; detailed history reveals that her son suddenly died 1 week ago.

Dissociative fugue

3-y/o boy with h/o of poor cuddling presents with severely delayed language and social development; PE reveals below normal intelligence with unusual calculating abilities and repetitive behaviors.

Autism

APPENDIX

Abbreviations

AA

amino acid

Ab

antibody

ABG

arterial-blood gas

ACE

angiotensin-converting enzyme

ACEi

ACE inhibitor

ACh

acetylcholine

ACL

anterior cruciate ligament

ACTH

adrenocortiotropic hormone

AD

autosomal dominant

ADH

antidiuretic hormone

ADHD

attention deficit hyperactivity disorder

ADP

adenosine diphosphate

AFP

α-fetoprotein

Ag

antigen

AIDS

acquired immunodeficiency syndrome

ALL

acute lymphocytic leukemia

ALP

alkaline phosphatase

ALS

amyotrophic lateral sclerosis

ALT

alanine transaminase

AML

acute myelogenous leukemia

ANA

antinuclear antibody

ANOVA

analysis of variance

ANS

autonomic nervous system

AR

autosomal recessive

ARB

angiotensin receptor blocker

ARDS

acute respiratory distress syndrome

ASA

aspirin

ASD

atrial septal defect

ASO

antistreptolysin O

AST

aspartate transaminase

ATN

ischemic acute tubular necrosis

ATP

adenosine triphosphate

ATPase

adenosine triphosphatase

AV

atrioventricular

AXR

abdominal x-ray

AZT

azidothymidine

BAL

British anti-Lewisite

BM

basement membrane

BP

blood pressure

BPG

bisphophoglycerate

BPH

benign prostatic hyperplasia

BR

bilirubin

BUN

blood urea nitrogen

Bx

biopsy

CA

cancer/carcinoma

CAD

coronary artery disease

cAMP

cyclic adenosine monophosphate

cANCA

cytoplasmic pattern of antineu trophil cytoplasmic antibodies

CBC

complete blood count

CCK

cholecystokinin

CEA

carcinoembryonic antigen

CF

cystic fibrosis

CFTR

cystic fibrosis transmembrane regulator

cGMP

cyclic guanosine monophosphate

CHF

congestive heart failure

CIN

cervical intraepithelial neoplasia

CK

serum creatine kinase

CLL

chronic lymphocytic leukemia

CML

chronic myelogenous leukemia

CMV

cytomegalovirus

CN

cranial nerve

CNS

central nervous system

CO

cardiac output

CoA

coenzyme A

COMT

catechol-O-methyltransferase

COPD

chronic obstructive pulmonary disease

COX

cyclooxygenase

Cp

concentration in plasma

CPK

creatine phosphokinase

Cr

creatinine

CRP

C-reactive protein

CSF

cerebrospinal fluid

CT

computed tomography

CV

cardiovascular

CVA

cerebrovascular accident or costovertebral angle

CXR

chest x-ray

D or DA

dopamine

d

day(s)

d/o

disorder

DAG

diacylglycerol

DES

diethylstilbesterol

DHT

dihydrotestosterone

DI

diabetes insipidus

DIC

disseminated intravascular coagulation

DIP

distal interphalangeal joint

DKA

diabetic ketoacidosis

DM

diabetes mellitus

DNA

deoxyribonucleic acid

DOE

dyspnea on exertion

DRE

digital rectal examination

ds

double stranded

DSM

diagnostic and statistical manual

DTR

deep tendon reflex

DTs

delerium tremens

DVT

deep venous thrombosis

E

epinephrine

EBV

Epstein-Barr virus

ECF

extracellular fluid

ECG

electrocardiogram

ECT

electroconvulsive therapy

EDV

end-diastolic volume

EEG

electroencephalogram

EF-2

elongation factor 2

EGD

esophagogastroduodenoscopy

ELISA

enzyme-linked immunosorbent assay

EM

electron microscopy

EOM

extraocular muscle

EPO

erythropoetin

EPS

extrapyramidal symptoms

ER

endoplasmic reticulum or emergency room

ESR

erythrocyte sedimentation rate

ESV

end-systolic volume

ETOH

ethanol

FAs

fatty acids

FAD

flavin adenine dinucleotide (oxidized)

FADH_2

flavin adenine dinucleotide (reduced)

FAP

familial adenomatous polyposis

FENa+

fractional excretion of sodium

FFP

fresh frozen plasma

FH

family history

FSH

follicle-stimulating hormone

FN

false negatives

FP

false positives

FTA-ABS

fluorescent treponemal antibody-absorbed

Fx

fracture

G3P

glucose-3-phosphate

G6PD

glucose-6-phosphate dehydrogenase

GABA

γ-aminobutyric acid

GBM

glomerular basement membrane

GCT

germ cell tumor

GFR

glomerular filtration rate

GGT

γ-glutamyl transpeptidase

GH

growth hormone

GI

gastrointestinal

Gi

G protein, inhibitory

GMP

guanosine monophosphate

GN

glomerulonephritis

GnRH

gonadotropin-releasing hormone

Gs

G protein, stimulatory

GSE

general somatic efferent

GTP

guanosine triphosphate

GU

genitourinary

GVE

general visceral efferent

HA

headache

Hb

hemoglobin

HBV

hepatitis B virus

hCG

human chorionic gonadotropin

HDL

high-density lipoprotein

HGPRT

hypoxanthine guanine phosphoryltransferase

HHV

human herpesvirus

HIV

human immunodeficiency virus

HMG-CoA

hydroxymethylglutaryl-CoA

h

hour(s)

h/o

history of

HPETE

hydroperoxyeicosatetraenoic acid

HPV

human papillomavirus

HR

heart rate

HRT

hormone replacement therapy

HSM

hepatosplenomegaly

HSV

herpes simplex virus

HTLV

human T-cell leukemia/lymphoma virus

HUS

hemolytic-uremic syndrome

HTN

hypertension

IBD

inflammatory bowel disease

ICAM

intracellular adhesion molecule

ICF

intracellular fluid

ICP

intracranial pressure

IF

intrinsic factor

Ig

immunoglobulin

IL

interleukin

IM

intramuscular

IND

indication(s)

INH

isoniazid

IOP

intraocular pressure

IP_3

inositol triphosphate

IPV

inactivated polio vaccine

IUGR

intrauterine growth retardation

IV

intravenous

IVC

inferior vena cava

IVIG

IV immunoglobulin

JG

juxtaglomerular

JVD

jugular venous distension

L

left

LAD

left anterior descending

LCA

left coronary artery

LDH

lactate dehydrogenase

LDL

low-density lipoprotein

LES

lower esophageal sphincter

LFT

liver function test

LH

leutinizing hormone

LLQ

left lower quadrant

LLSB

left-lower sternal border

LMN

lower motor neuron

LP

lumbar puncture

LPS

lipopolysaccharide

LT

leukotriene

LUSB

left-upper sternal border

LUQ

left upper quadrant

LV

left ventricle

MAOI

monoamine oxidase inhibitor

MCA

middle cerebral artery

MCP

metacarpel phalangeal

MCL

medial collateral ligament

MCV

mean corpuscular volume

MEN

multiple endocrine neoplasia

MHC

major histocompatibility complex

MI

myocardial infarction

MLF

medial longitudinal fasciculus

mm

millimeters or muscles

MMR

measles, mumps, rubella

MOA

mechanism of action

MPTP

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MRI

magnetic resonance imaging

MS

multiple sclerosis

MTP

metatarsal-phalangeal

MVA

motor vehicle accident

NAD

nicotinamide adenine dinucleotide (oxidized)

NADH

nicotinamide adenine dinucleotide (reduced)

NADP

nicotinamide adenine dinucleotide phosphate (oxidized)

NADPH

nicotinamide adenine dinucleotide phosphate (reduced)

NE

norepinephrine

NSAID

nonsteroidal anti-inflammatory drug

N/V

nausea/vomiting

OAA

oxaloacetic acid

OCP

oral contraceptive pills

OPV

oral polio vaccine

PABA

para-aminobenzoic acid

PAF

platelet activity factor

PAH

para-aminohippuric acid

PALS

periarterial lymphoid sheath

PAN

polyarteritis nodosa

P-ANCA

perinuclear pattern of antineutrophil cytoplasmic antibodies

PAS

periodic acid-Schiff (stain)

PBS

peripheral blood smear

PCAM

platelet cell adhesion molecule

PCI_2

prostacyclin I_2

PCL

posterior cruciate ligament

PCP

phencyclidine hydrochloride

PCR

polymerase chain reaction

PCWP

pulmonary capillary wedge pressure

PDA

patent ductus arteriosus

PDE

phosphodiesterase

PDGF

platelet-derived growth factor

PE

physical examination

PFK

phosphofructokinase

PFT

pulmonary function tests

PG

prostaglandin

PID

pelvic inflammatory disease

PIP

proximal interphalangeal

PIP_2

phosphatidylinositol-4,5-bisphosphonate

PK

pyruvate kinase

PKU

phenylketonuria

PMN

polymorphonuclear

PNH

paroxysmal nocturnal hemoglobinuria

PNS

peripheral nervous system

PPi

pronton-pump inhibitor

PPRF

parapontine reticular formation

PSA

prostate-specific antigen

PT

prothrombin time

PTH

parathyroid hormone

PTT

partial thromboplastin time

PVD

peripheral vascular disease

R

right

RA

right atrium

RAA

Renin angiotensin aldosterone

RBC

red blood cell

RBF

renal blood flow

RCA

right coronary artery

REM

rapid eye movement

RER

rough endoplasmic reticulum

RF

rheumatoid factor

RLQ

right lower quadrant

ROM

range of motion

RPF

renal plasma flow

RPR

rapid plasma reagin

RR

respiratory rate

RSV

respiratory syncytial virus

RUQ

right upper quadrant

RV

right ventricle

RVH

right ventricular hypertrophy

s

second(s)

S1(2,3,4)1st

heart sound (2nd, 3rd, 4th)

SA

sinoatrial

SC

subcutaneous or sickle cell

SD

standard deviation

SEM

standard error of the mean

SES

socioeconomic status

SGOT

serum glutamic oxaloacetic transaminase

SGPT

serum glutamic pyruvate transaminase

SLE

systemic lupus erythematosus

SMX

sulfamethoxazole

SOB

shortness of breath

ss

single stranded

SSA

special somatic afferent

SSPE

subacute sclerosing panencephalitis

SSRI

selective serotonin reuptake inhibitor

STD

sexually transmitted disease

SV

stroke volume

SVA

special visceral afferent

SVT

supraventricular tachycardia

Sx

symptom(s)

s/p

status post

t1/2

half-life

T_3

triiodothyronine

T_4

thyroxine

TB

tuberculosis

TBW

total body water

TG

triglyceride

TIBC

total iron binding capacity

TMP

trimethoprim

TN

true negatives

TNF

tissue necrosis factor

TNM

tumor node metastasis

TOX

toxicity

TP

true positives

tPA

tissue plasminogen activator

TPR

total peripheral resistance

TRH

thyrotropin-releasing hormone

TSH

thyroid-stimulating hormone

TSS

toxic shock syndrome

TTP

thrombotic thrombocytopenic purpura

Tx

treatment/therapy

TXA

thromboxane

UA

urinalysis

UMN

upper motor neuron

UGI

upper GI

URI

upper respiratory infection

UTI

urinary tract infection

U/S

ultrasound

Vd

volume of distribution

VCAM

vascular cell adhesion molecule

VDRL

venereal disease research laboratory

Vfib

ventricular fibrillation

VHL

von Hippel-Lindau

VLDL

very low-density lipoprotein

VMA

vanillylmandelic acid

V/Q

ventilation/perfusion ratio

VSD

ventricular septal defect

vWF

von Willebrand factor

VZV

varicella-zoster virus

WBC

white blood cell

WNL

within normal limits

XL

x-linked

XR

x-ray

y/o

year-old

ZE

Zollinger-Ellison

5-FU

5-fluorouracil

5-HIAA

5-hydrocyindoleacetic acid

5-HT

5-hydroxytryptamine (serotonin)

↑

High or increases

↓

Low or decreases

→

Leads to or causes

1°/2°/3°

primary/secondary/tertiary

~

Approximately

⊕

positive

>>>

much greater than

much less than

Index

A

Abetalipoproteinemia

Abruptio placentae

Abscess

Absorption, drug

Acanthosis nigricans

Accuracy

ACE inhibitors. See Angiotensin-converting enzyme inhibitors

Acebutolol

Acetaminophen (Tylenol)

Acetazolamide

Acetylcholine (ACh)

Acetylcholinesterase poisoning

ACh. See Acetylcholine

Achalasia

Achondroplasia

Acid-base disturbances

Acidosis

Acinus of the lung

Acne vulgaris

Acquired immunodeficiency syndrome (AIDS)

Acromegaly

ACTH. See Adrenocorticotropic hormone

Actinomyces

Activator

Acute postinfectious glomerulonephritis

Acute renal failure (ARF)

Acyclovir

AD disorders. See Autosomal dominant disorders

Addison disease

Adenocarcinoma

Adenomas

Adenosine deaminase deficiency

Adenosine triphosphate (ATP)

Adenovirus

ADH. See Antidiuretic hormone

ADHD. See Attention deficit hyperactivity disorder

Adipose tissue

Adjustment disorder

ADPKD. See Autosomal dominant polycystic kidney disease

Adrenal glands

Adrenocortical insufficiency

Adrenocorticotropic hormone (ACTH)

Adrenogenital syndromes

Adrenoleukodystrophy

Adriamycin

Adult respiratory distress syndrome (ARDS)

African sleeping sickness

Aging

Agonist

AIDS. See Acquired immunodeficiency syndrome

Alanine

Albendazole

Albinism

Albuterol

Alcohol

abuse

teratogenic effects

Alcoholic dilated cardiomyopathy

Aldosterone

Alkalinze urine

Alkalosis

Alkaptonuria

Allergic bronchopulmonary aspergillosis

Allopurinol

α-Glucosidase inhibitor

α-Methyldopa

α-Tocopherol

Alport syndrome

ALS. See Amyotrophic lateral sclerosis

Aluminum hydroxide

Aluminum sucrose sulfate

Alzheimer disease

Amantadine

Amenorrhea

Amiloride

Amino acids

Aminocaproic acid

Aminoglycosides

Aminolevulinate synthase

Amiodarone

Amitriptyline

Amnesia

Amniotic fluid embolism

Amoxapine

Amoxicillin

Amphetamine

Amphotericin

Ampicillin

Amprenavir

Amyloidoses

Amyotrophic lateral sclerosis (ALS)

ANA. See Antinuclear antibodies

Anaclitic depression

Analgesics

Analysis of variance (ANOVA)

Anaphylactic shock

Anaplastic carcinoma

Anatomic snuffbox

Anatomy

cardiovascular system

connective tissues

endocrine system

gastrointestinal system

genitourinary system

musculoskeletal system

reproductive system

respiratory system

skin

Androgen insensitivity syndrome

Anemia

Anemic infarcts

Anencephaly

Anesthetics

Aneurysms

Angina

Angiodysplasia

Angiotensin II

Angiotensin receptor blockers (ARBs)

Angiotensin-converting enzyme (ACE) inhibitors

Ankylosing spondylitis

Anorexia nervosa

ANOVA. See Analysis of variance

Antacids

Anterior pituitary

Anthracosis

Anthrax

Antiacetylcholine esterase

Antianginal agents

Antiarrhythmics

Antibiotics. See also specific drugs

Anticholinergic agents

Anticholinesterases

Anticoagulants

Antidepressants

Antidiuretic hormone (ADH)

Antiepileptics

Antihistamines

Antihypertensives

Antinuclear antibodies (ANA)

Antiparkinsonian agents

Antiphospholipid antibody syndrome

Antipsychotics

Antisocial personality disorders

Antiviral agents. See also specific drugs

Anxiety

Aortic dissection

Aortic regurgitation

Aortic stenosis

Apgar score

Aplasia

Apolipoprotein

Apoptosis

Appendicitis

Apraxia

AR disorders. See Autosomal recessive disorders

Arachidonic acid

Arboviruses

ARBs. See Angiotensin receptor blockers

Arenaviridae

ARF. See Acute renal failure

Argyll-Robertson pupil

Arnold-Chiari malformation

Arsenic

Arteriolosclerosis

Artery(ies)

CNS

coronary

in stroke

Arthritis

Asbestosis

Ascending cholangitis

Aschoff bodies

Ascorbic acid

ASD. See Atrial septal defect

Asperger syndrome

Aspergillus sp.

Aspirin (salicylates)

Asthma

Astrovirus

Ataxia-telangiectasia

Atelectasis

Atenolol

Atherosclerosis

ATP. See Adenosine triphosphate

Atracurium

Atrial fibrillation

Atrial myxoma

Atrial natriuretic peptide

Atrial septal defect (ASD)

Atrophy

Atropine

Attention deficit hyperactivity disorder (ADHD)

Auerbach plexus. See Myenteric plexus

Autism

Autoantibodies

Autoimmune connective tissue disorders

Automaticity

Autonomics

Autoregulation

Autosomal dominant (AD) disorders

Autosomal dominant polycystic kidney disease (ADPKD)

Autosomal recessive (AR) disorders

Aversive conditioning

Avoidant personality disorders

Axonal transport

Azithromycin

Azole family

AZT. See Zidovudine

B

B lymphocyte

Babesia

Babinski reflex

Bacillus

Bacteria. See also specific bacteria

binding and phagocytosis of

gram-positive

infectious diseases from

taxonomy

Bacterial vaginosis

Bacteroides

Bactrim

Balanitis

Bang disease

Barbiturates

Barrett’s esophagus

Bartter syndrome

Basal cell carcinoma

Basophil

Beckwith-Wiedemann syndrome

Beclomethasone

Behavioral neurochemistry

Beneficence

Benign prostatic nodular hyperplasia

Benzodiazepines

Benztropine

Beriberi

Bernard-Soulier disease

Berry aneurysm

α-Agonists

β-Blockers

β-Endorphin

β-Lactam antibiotics

β-Lactamase inhibitors

Betamethasone

Bethanechol

Bias

Bicarbonate

Bicuspid aortic valve

Bile

Biliary atresia

Bilirubin

Biostatistics

Biotin

Bipolar disorder

Bismuth subsalicylate

Black fever

Bleomycin

Blood pressure maintenance

Body dysmorphic disorder

Boerhaave syndrome

Bone

fractures

neoplasia of

nonneoplastic disorders

osteomyelitis

Borderline personality disorders

Bordetella pertussis

Borrelia

Botulinum

Brachial plexus

Brain tumors

Branchial arches

Breast disorders

Bretylium

Brief psychotic disorder

Brodmann areas

Bromocriptine

Bronchiectasis

Bronchitis

Bronchodilators

Brucella

Bubonic plague

Buccopharyngeal membrane

Budd-Chiari syndrome

Buerger disease

Bulimia

Bulla

Bullous pemphigoid

Bunyaviridae

Bupivacaine

Bupropion

Burns

Busulfan

C

Calcitonin

Calcium

Calcium channel blockers

Calcium regulation

Calicivirus

cAMP. See Cyclic adenosine monophosphate

Campylobacter jejuni

Cancer. See specific types and organs

Candida albicans

Candidiasis

Carbamazepine

Carbidopa

Carbohydrates

Carbon monoxide

Carcinogens

Carcinoid syndrome

Carcinoid tumors

Carcinoma. See specific types and organs

Cardiac contractility and output

Cardiac electrophysiology

Cardiac infectious disorders

Cardiac muscle

Cardiac tumors

Cardiogenic shock

Cardiomyopathy. See also Hypertrophic cardiomyopathy

Cardiovascular system

anatomy

disorders

aneurysms

arteriolosclerosis

atherosclerosis

cardiac tumors

cardiomyopathy

case presentations

congenital heart disease

dissection

heart failure

hypertension

infectious

ischemic heart disease

murmurs

pericarditis

vascular tumors

vasculitides

embryology

pharmacology

antianginal agents

antiarrhythmics

antihypertensives

autonomics

inotropic support

lipid-lowering agents

physiology

Case-control study

Catscratch disease

Cauda equina syndrome

CCK. See Cholecystokinin

CDR. See Complementary determining region

Ceftriaxone

Celecoxib

Celiac disease

Cell changes/accumulations

Cell cycle

Cell injury

Cell membranes

Cellular adaptations

Central nervous system (CNS)

arteries

cerebellum, thalamus, hypothalamus of

cerebral cortex

cranial nerves

energy sources

lymphoma

spinal tracts

Cephalosporins

Cerebellar cortex

Cerebellum

Cerebral cortex

Cerebral ischemia

Cerebrospinal fluid (CSF)

Cervical carcinoma

Cervical intraepithelial neoplasia (CIN)

CF. See Cystic fibrosis

Chancroid

Chediak-Higashi disease

Chemotherapeutic agents

CHF. See Congestive heart failure

Child abuse

Childhood psychiatric disorders

Chi-squared test

Chlamydia

Chloramphenicol

Chloroquine

Chlorpromazine

Chlorpropamide

Cholangiocarcinoma

Cholangitis

Cholecystitis

Cholecystokinin (CCK)

Cholelithiasis

Cholesterol

Cholesterolosis

Cholestyramine

Chondroma

Chondrosarcoma

Choriocarcinoma

Chorion

Chromosomes

Chronic granulomatous disease

Chronic obstructive pulmonary disease (COPD)

Churg-Strauss syndrome

Cimetidine

CIN. See Cervical intraepithelial neoplasia

Ciprofloxacin

Cirrhosis

Cisplatin

Citalopram

Citric acid cycle

Classical conditioning

Clavulanic acid

Clearance

Cleft lip, palate

Clindamycin

Clinical testing

Clofazimine

Clofibrate

Clomiphene

Clomipramine

Clonidine

Clopidogrel

Clostridium

Clozapine

CMV. See Cytomegalovirus

CNS. See Central nervous system

Coagulopathy

Cobalamin

Cocaine

Coccidioides immitis

Coccidioidomycosis

Cohort study

Colchicine

Collagen

Collecting tubule

Colon

Colon carcinoma

Common bile duct

Common variable immunodeficiency

Compartment syndrome

Complement system

Complementary determining region (CDR)

Complementation

Conduction velocity

Condyloma acuminatum

Cones

Confidentiality

Confirmatory test

Congenital heart disease

Congestive heart failure (CHF)

Conjunctivitis

Conn syndrome

Connective tissues

anatomy

disorders

embryology

histology

Construction apraxia

Contrecoup injury

Conversion disorder

COPD. See Chronic obstructive pulmonary disease

Cor pulmonale

Cori cycle

Coronary arteries

Coronary occlusion

Corticosteroids

Cortisol

Cortisone

Corynebacterium

Countertransference reaction

Coup injury

Courvoisier law

COX pathway

Coxsackie viruses

Cranial nerves

Craniopharyngioma

CREST syndrome

Cretinism

Creutzfeldt-Jacob disease

Crigler-Najjar syndrome

Crocodile tears syndrome

Crohn’s disease

Cromolyn

Croup

Cryptococcosis

Cryptorchidism

Cryptosporidium

CSF. See Cerebrospinal fluid

Cyanide

Cyanocobalamin

Cyclic adenosine monophosphate (cAMP)

Cyclophosphamide

Cyclothymia

Cystic fibrosis (CF)

Cysticercosis

Cystinuria

Cystosarcoma phyllodes

Cytarabine

Cytogenetic disorders

Cytokines

Cytomegalovirus (CMV)

D

Dandy-Walker malformation

Dantrolene

Dapsone

ddC. See Zalcitabine

ddI. See Didanosine

Deafness

Death

Decerebrate rigidity

Decorticate rigidity

Deferoxamine

Delavirdine

Deletion disorder

Delirium

Delirium tremens

Delusion

Demeclocycline

Dementia

Demyelinating disorders

Dental caries

Denys-Drash syndrome

Depression

Dermatitis

Dermatomyositis

DES. See Diethylstilbestrol

Desipramine

Desmopressin

Developmental stages

Dexamethasone

d4T. See Stavudine

Diabetes

Diabetic glomerulosclerosis

Diabetic ketoacidosis

Dialysis

Diaphragm

Diarrhea

Diastolic blood pressure

Diazepam

DIC. See Disseminated intravascular coagulation

Didanosine (ddI)

Diethylcarbamazine

Diethylstilbestrol (DES)

DiGeorge syndrome. See Thymic aplasia

Digitalis

Digoxin

Dilantin

Dilated cardiomyopathy

Diltiazem

Dimercaprol

Dinoprostone

Diphenhydramine

Diphenoxylate

Diphyllobothrium latum

Disaccharide deficiency

Discoid lupus erythematosus

Disease prevention

Disopyramide

Dissection

Disseminated intravascular coagulation (DIC)

Dissociative identity disorder

Distribution, drug

Disulfide bonds

Disulfiram

Diuretics

Diverticular disease

Divorce

DNA

mutations

replication

transfer procedures

viruses

Dobutamine

Dopamine

Dose-response curve

Down syndrome

Doxazosin

Doxepin

Doxorubicin

Doxycycline

Drug development. See also Pharmacology

Dubin-Johnson syndrome

Ductal carcinoma

Dumping syndrome

Duodenal atresia

Duodenal ulcer

Duodenum

Durable power of attorney

Dysfunctional uterine bleeding

Dyssomnia

Dystrophic calcification

E

Ebstein anomaly

EBV. See Epstein-Barr virus

ECF. See Extracellular fluid

Echinococcus granulosus

Echothiophate

Eclampsia

Ectoderm

Ectopic pregnancy

Edema

Edrophonium

Efavirenz

Effective dose

Efficacy

Ego

Ehlers-Danlos syndrome

Ejection fraction

Elder abuse

Elimination, drug

ELISA. See Enzyme-linked immunosorbent assay

Embolism

Embryology

cardiovascular system

connective tissues

endocrine system

gastrointestinal system

general

genitourinary system

nervous system

red blood cell production

reproductive system

respiratory system

skin

Emphysema

Encainide

Encephalitis

Encephalocele

Enchondroma

Endocarditis

Endocrine system

anatomy

disorders

adrenal

adrenogenital syndromes

case presentations

diabetes

pancreatic endocrine tumors

parathyroid

pituitary

thyroid

embryology

kidney

pharmacology

adrenal gland

diabetes

parathyroid

pituitary

thyroid

physiology

Endoderm

Endometrial carcinoma

Endometriosis

Endotoxin

Enhancer

Enkephalins

Entamoeba histolytica

Enteric nervous system

Enterobacter

Enterobius vermicularis

Enterococcus

Enuresis

Enzyme-linked immunosorbent assay (ELISA)

Enzymes

Eosinophil

Eosinophilic granuloma

Ependymoma

Ephedrine

Epidemiology

Epididymis

Epididymitis

Epidural hematoma

Epiglottitis

Epilepsy

Epinephrine

Epispadias

Epstein-Barr virus (EBV)

Eptifibatide

Erb-Duchenne palsy

Erythema infectiosum

Erythema multiforme

Erythromycin

Erythropoietin

Escherichia coli

Escitalopram

Esmolol

Esophageal atresia

Esophageal carcinoma

Esophageal varices

Esophagus

Essential fructosuria

Essential thrombocytosis

Estrogen

Ethacrynic acid

Ethics

Ethosuximide

Ethylene glycol

ETOH. See Hepatic ethanol

Etoposide

Ewing sarcoma

Exotoxins

Exstrophy of the bladder

Extinction

Extracellular fluid (ECF)

Exudate

F

Fabry disease

Facial nerve

Factitious disorder

Factor V Leiden

Factor XIIa

Fallopian tube

Familial adenomatous polyposis (FAP)

Familial hypercholesterolemia

Famotidine

Fanconi syndrome

FAP. See Familial adenomatous polyposis

Fat digestion

Fat emboli

Fatal familial insomnia

Fat-soluble vitamins

Felty syndrome

Female reproductive system disorders

Fetal alcohol syndrome

Fetal hydantoin syndrome

Fibroadenoma

Fibrocystic change

Fibrous dysplasia

Filoviridae

Finasteride

First-pass metabolism

Fitz-Hugh and Curtis syndrome

Flecainide

Flexor withdrawal reflex

Fluconazole

Flucytosine

Flumazenil

Fluorescent treponemal antibody-absorption test (FTA-ABS)

Fluoroquinolones

Fluoxetine

Flutamide

Fluticasone

Fluvoxamine

Focal-segmental glomerulonephritis (FSGN)

Folate

Folic acid deficiency

Follicle-stimulating hormone (FSH)

Follicular carcinoma

Fomepizole

Foregut

Foscarnet

Fractures

Fragile X syndrome

Francisella

Frank-Starling relationship

Freudian theory

Frey syndrome

Friedreich ataxia

Frotteurism

Fructose intolerance

FSGN. See Focal-segmental glomerulonephritis

FSH. See Follicle-stimulating hormone

FTA-ABS. See Fluorescent treponemal antibody-absorption test

Fungi

Furosemide

G

Gait apraxia

Galactosemia

Gall bladder disorders

Gallstone

Ganciclovir

Gardner syndrome

Gardnerella vaginalis

Gastric acid

Gastric carcinoma

Gastric inhibitory peptide (GIP)

Gastric ulcer

Gastrin

Gastritis

Gastrocolic reflex

Gastrointestinal (GI) system

alcoholism influencing

anatomy

disorders

case presentations

diverticular disease

gall bladder

gastritis

infectious diarrhea

inflammatory bowel disease

liver

malabsorption

neoplastic

nonneoplastic

pancreatic cancer

pancreatitis

pediatric

peptic ulcer disease

viral hepatitis

embryology

pharmacology

physiology

Gaucher disease

Gemfibrozil

Genes

Genitalia

Genitourinary system. See also Kidney(s)

anatomy

disorders

acid-base disturbances

acute renal failure

case presentations

glomerulonephropathies

nephrotic and nephritic syndromes

polycystic kidney disease

renal infections

renal tubular acidosis

renal tumors

renal vascular disease

tubulointerstitial diseases

urinary system

urinary tract tumors

urolithiasis

embryology

pharmacology

physiology

Gentamicin

Genu

GERD

Germinoma

Gestational choriocarcinoma

GFAP. See Glial fibrillary acidic protein

GFR. See Glomerular filtration rate

GH. See Growth hormone

GHRH. See Growth hormone-releasing hormone

GI lymphomas

GI system. See Gastrointestinal system

Giant cell tumor of bone

Giardia lamblia

Gigantism. See Increased linear growth

Gilbert syndrome

GIP. See Gastric inhibitory peptide

Glanzmann thrombasthenia

Glial fibrillary acidic protein (GFAP)

Glioblastoma multiforme

Glitazones

Glomerular filtration rate (GFR)

Glomerulonephropathies

Glucagon

Glucocorticoids

Gluconeogenesis

Glucose-6-phosphate dehydrogenase

Glutamine synthetase

Glyburide

Glycine

Glycogen storage diseases

Glycogenolysis

Glycolysis

Glyconeogenesis

Goiter

Golgi tendon organs

Golgi tendon reflex

Gonococcal arthritis

Gonorrhea

Goodpasture syndrome

Gout

Grafts

Graft-versus-host disease

Gram-positive bacteria

Granisetron

Granuloma inguinale

Grapefruit

Graves disease

Griseofulvin

Growth hormone (GH)

Growth hormone-releasing hormone (GHRH)

GTP. See Guanosine triphosphate

Guanethidine

Guanosine triphosphate (GTP)

Guillain-Barré syndrome

H

HAART. See Highly active antiretroviral therapy

Haemophilus ducreyi

Haemophilus influenzae

Hageman factor. See Factor XIIa

Half-life, drug

Hallucination

Haloperidol

Halothane

hand-foot-and-mouth disease

Hand-Schüller-Christian disease

Hansen disease

Hantavirus

Hapten

Hartnup disease

Hashimoto disease

Haustra

Health insurance portability and accountability act (HIPAA)

Heart

amyloidosis influencing

disease

energy sources

failure

sounds

Helicobacter pylori

HELLP syndrome

Helminths

Hemangioblastoma

Hemangiosarcoma

Hematology

Heme

Hemicholinium

Hemochromatosis

Hemodynamic dysfunction

Hemoglobin

Hemolytic uremic syndrome (HUS)

Hemophilia

Hemorrhages

Hemosiderin

Hemostasis

Henoch-Schönlein purpura

Heparin

Hepatic adenoma

Hepatic ethanol (ETOH)

Hepatic failure

Hepatitis

Hepatitis A

Hepatitis B

Hepatitis C

Hepatitis E

Hepatocellular carcinoma

Hereditary hemorrhagic telangiectasia

Hereditary nonpolyposis colorectal carcinoma (HNPCC)

Hernias

Herpes genitalis

Herpes labialis

Herpes simplex virus (HSV)

Herpes zoster ophthalmicus

Herpesviridae

HHV. See Human herpesvirus

High altitude, acclimatization to

Highly active antiretroviral therapy (HAART)

HIPAA. See Health insurance portability and accountability act

Hirschsprung disease

Histamine

Histiocytosis X

Histones

Histoplasma capsulatum

Histoplasmosis

Histrionic personality disorders

HIV. See Human immunodeficiency virus

HLA subtypes

HNPCC. See Hereditary nonpolyposis colorectal carcinoma

Hodgkin disease

Homocystinuria

Hormones. See also specific hormones

Horner syndrome

Horseshoe kidney

Hospice care

Hot-tub folliculitis

HPV. See Human papillomavirus

HSV. See Herpes simplex virus

HTLV. See Human T-cell leukemia/lymphoma virus

HTN. See Hypertension

Human herpesvirus (HHV)

Human immunodeficiency virus (HIV)

Human papillomavirus (HPV)

Human T-cell leukemia/lymphoma virus (HTLV)

Hunter syndrome

Huntington disease

Hurler syndrome

HUS. See Hemolytic-uremic syndrome

Hydralazine

Hydrocele

Hydrocephalus

Hydrocortisone

Hydrops fetalis

Hydroxylase deficiencies

Hyperaldosteronism

Hyperbilirubinemia

Hypercalcemia

Hypercorticism (Cushing syndrome)

Hyperemia

Hyper-IgM syndrome

Hyperparathyroidism

Hyperplasia

Hyperpolarization

Hypersensitivity reactions

Hypertension (HTN)

Hyperthyroidism

Hypertrophic cardiomyopathy

Hypertrophy

Hypervariable region

Hypochondriasis

Hypoglycemia

Hypomania

Hypoparathyroidism

Hypoplasia

Hypospadias

Hypothalamus

Hypothenar eminence

Hypothyroidism

Hypovolemic shock

Hypoxic encephalopathy

I

Ibutilide

ICAM. See Intercellular adhesion molecule

I-cell disease

ICF. See Intracellular fluid

Id

Ideas of reference

Idiopathic pulmonary fibrosis

Idiopathic thrombocytopenia

IF. See Intrinsic factor

Ig. See Immunoglobulins

IL-. See Interleukins

Ileum

Illusion

Imipramine

Immune system

autoantibodies

cells

disorders

hypersensitivity reactions

immunoglobulins in

transplant rejection and

Immunodeficiencies

Immunoglobulins (Ig)

Impetigo

Imprinting

Incidence

Inclusions

Increased linear growth (gigantism)

Indinavir

Indomethacin

Infarcts

Infectious diarrhea

Infectious diseases. See also specific diseases

bacterial

cardiac

case presentations

fungal

protozoal

viral

Infective endocarditis

Inflammation

Inflammatory bowel disease

Influenza

Informed consent

Inherited diseases

Inotropic support

Insulin

Insulinoma

Intention tremor

Intercellular adhesion molecule (ICAM)

Interferon-α

Interleukins (IL-)

Interstitial nephritis

Intestines

Intracellular fluid (ICF)

Intracranial hemorrhage

Intraductal papilloma

Intranuclear ophthalmoplegia

Intrinsic factor (IF)

Intussusception

Inversion disorder

Iodoquinol

Ipratropium

Iron

Ischemic heart disease

Ischemic/hypoxic cell injury

Isocarboxazid

Isoniazid

Isonicotinic acid

Isoproterenol

Isotretinoin

Ivermectin

J

Jarisch-Herxheimer reaction

Jaundice

JC virus

Jejunum

Job syndrome

Joints

Juvenile pilocytic astrocytoma

K

Kallmann syndrome

Kaposi sarcoma

Kartagener syndrome

Kawasaki disease

Keloid

Keratoacanthoma

Keratosis

Ketamine

Ketoconazole

Kidney(s)

disorders

endocrine functions of

horseshoe

pharmacology

Kimmelstiel-Wilson disease

Klebsiella

Klinefelter syndrome

Klüver-Bucy syndrome

Korsakoff psychosis

Krabbe disease

Kübler-Ross stages of dying

Kuru

Kwashiorkor

L

Labetalol

Lactobacillus

Lactose intolerance

Lactulose

Lacunar infarctions

Lambert-Eaton syndrome

Lamivudine (3TC)

Lamotrigine

Langerhans cells

Lansoprazole

Large cell carcinoma

Laryngotracheobronchitis

Lateral epicondylitis

Learned helplessness

Left MCA cerebrovascular accident

Legg-Calvé-Perthes disease

Legionella

Leiomyoma

Leiomyosarcoma

Leishmania

Leprosy

Lesch-Nyhan Syndrome

Lethal dose

Leukemia

Leukocytes

Leukodystrophies

Leukotriene inhibitors

Leuprolide

Levodopa

Levofloxacin

Levothyroxine

LH. See Luteinizing hormone

Lichen planus

Lidocaine

Life cycle

Ligaments

Linitis plastica

Lipid metabolism

Lipid-lowering agents

Lipofuscin

Lipogenesis

Listeria

Lithium

Liver

disorders

energy sources

metabolism and

nutmeg

Living will

Loa loa

Loading dose

Lobular carcinoma

Local anesthetics

Locked-in syndrome

Loose association

Loperamide

Loratadine

Losartan

Low birth weight

Lung(s). See also Respiratory system

capacity and volume

compliance and resistance

disorders

zones

Luteinizing hormone (LH)

Lyme disease

Lymph nodes

Lymphocytes

Lymphogranuloma venereum

Lymphomas

M

Macrolides

Macrophages

Macule

Mad cow disease

Magnesium hydroxide

Major depressive disorder (MDD)

Malabsorption

Malabsorption syndromes

Malakoplakia

Malaria

Malassezia furfur

Male reproductive system disorders

Male sexual response cycle

Malignant melanoma

Malignant mesothelioma

Malingering

Mallory-Weiss tear

Malpractice

Mania

Mannitol

MAOIs

Maple syrup urine disease

Marasmus

Marcus Gunn pupil

Marfan syndrome

Marijuana

Massive pulmonary embolus

Mastitis

McCune-Albright syndrome

MDD. See Major depressive disorder

Measles virus (rubeola)

Mebendazole

Meckel diverticulum

Meclizine

Meconium ileus

Medicaid

Medical ethics

Medicare

Medulloblastoma

Mefloquine

Meissner corpuscle

Meissner plexus. See Submucosal plexus

Melanin

Melanoma

Melarsoprol

Melasma

Melatonin

MEN syndrome. See Multiple endocrine neoplasia syndrome

Ménétrier disease

Meninges

Meningioma

Meningitis

Meningocele

Menopause

Menstrual cycle

Meperidine

6-mercaptopurine

Merkel tactile disc

Mesna

Mesoderm

Meta-analysis

Metabolic acidosis

Metabolism

carbohydrate, protein, and lipid

drug

Metabolites

Metachromatic leukodystrophy

Metaplasia

Metastases

Metastatic calcification

Metformin

Methadone

Methanol

Methemoglobin

Methimazole

Methotrexate

Methylene blue

Methylprednisolone

Metoclopramide

Metoprolol

Metronidazole

Mexiletine

MGUS. See Monoclonal gammopathy of undetermined significance

MHC molecules

MI. See Myocardial infarction

Michaelis-Menten kinetics

Miconazole

Microbiology

Microglia

Microscopic polyangiitis

Midazolam

Midgut

Mifepristone

Migraine

Military TB

Minimal change disease

Minors

Minoxidil

Mirtazapine

Misoprostol

Mitral regurgitation

Mitral stenosis

Mitral valve

prolapse

Mixed connective tissue disease

Molecular biology techniques

Moles

Molluscum contagiosum

Monoclonal gammopathy of undetermined significance (MGUS)

Monocytes

Mononucleosis

Montelukast

Mood disorders

Morphine

Mosaicism

Motor fibers

Mucor sp.

Mucormycosis

Multi-infarct dementia

Multiple endocrine neoplasia (MEN) syndrome

Multiple myeloma

Multiple sclerosis

Mumps virus

Mural thrombus

Murmurs

Musculoskeletal system

anatomy

disorders

arthritis

case presentations

neoplasia of bone

nonneoplastic bone

physiology

Mutations

Myasthenia gravis

Mycobacterium avium-intracellulare

Mycobacterium leprae

Mycobacterium scrofulaceum

Mycobacterium tuberculosis

Mycology

Mycoplasma pneumoniae

Mycosis fungoides

Myelofibrosis

Myelomeningocele

Myeloproliferative disorders

Myenteric (Auerbach) plexus

Myocardial infarction (MI)

Myositis

Myotonic dystrophy

N

Nalbuphine

Naloxone

Naltrexone

Narcissistic personality disorders

Narcolepsy

NE. See Norepinephrine

Necrosis

Negative predictive value

Neisseria gonorrhea

Neisseria meningitides

Nelfinavir

Neocortex

Neonatal respiratory distress syndrome (RDS)

Neoplasia of bone

Neoplastic disorders

Neoplastic polyp

Neostigmine

Nephron, functional regions of

Nephrosclerosis

Nephrotic and nephritic syndromes

Nervous system. See also Central nervous system

disorders

brain tumors

congenital

demyelinating

encephalitis

intracranial hemorrhage

leukodystrophies

meningitis

miscellaneous

neurocutaneous syndromes

neurodegenerative

seizures

spinal cord

stroke

embryology

enteric

parasympathetic

pharmacology

analgesics

anesthetics

antiepileptics

antiparkinsonian agents

sympathetic

Neuroblastoma

Neurocutaneous syndromes

Neurodegenerative disorders

Neurofibromatosis

Neurogenic shock

Neuroleptic malignant syndrome (NMS)

Neurotransmitters

Neutrophils

Nevirapine

Niacin

Niclosamide

Niemann-Pick disease

Nifedipine

Nifurtimox

Nitrate

Nitrates

Nitric oxide (NO)

Nitrofurantoin

Nitroprusside

Nitrosoureas

Nitrous oxide

Nizatidine

NMS. See Neuroleptic malignant syndrome

NO. See Nitric oxide

Nocardia

Nodule

Nondisjunction disorder

Nongonococcal septic arthritis

Non-Hodgkin lymphoma

Nonmaleficence

Nonneoplastic bone disorders

Nonneoplastic GI disorders

Nonnucleoside RT inhibitors

Nonsteroidal anti-inflammatory drugs (NSAIDS)

Norepinephrine (NE)

Northern blot

Nortriptyline

Norwalk virus

NSAIDS. See Nonsteroidal anti-inflammatory drugs

Nucleoside RT inhibitors

Null hypothesis

Nutmeg liver

Nutrition

Nystatin

O

Oat cell carcinoma

Obese

Obsessive-compulsive disorder (OCD)

Obstructive lung disease

Obstructive sleep apnea

OCD. See Obsessive-compulsive disorder

OCPs. See Oral contraceptives

Octreotide

Odds ratio

Oedipus complex

Olanzapine

Oligodendrocyte

Oligodendroma

Omeprazole

Onchocerca volvulus

Ondansetron

Operant conditioning

Operon

Opioids

Opisthorchis sinensis

Oppositional defiant disorder

Opsonization

Oral advance directive

Oral contraceptives (OCPs)

Oral hairy leukoplakia

Oral hypoglycemics

Organophosphates

Orthomyxoviridae

Oseltamivir

Osgood-Schlatter disease

Osler nodes

Osteitis fibrosa cystica

Osteoarthritis

Osteoblastoma

Osteochondroma

Osteogenesis imperfecta

Osteoma

Osteomalacia

Osteomyelitis

Osteopetrosis

Osteoporosis

Osteosarcoma

Otitis

Ovarian carcinoma

Ovarian cysts

Ovarian neoplasm

Ovarian tumors

Oxytocin

P

P value

Pacinian corpuscle

Paclitaxel

Paget disease

Palmar reflex

Pancoast syndrome

Pancreas

Pancreatic cancer

Pancreatic duct

Pancreatic endocrine tumors

Pancreatitis

Panic disorder

Pantoprazole

Pantothenate

Pantothenic acid

Papez circuit

Papillary carcinoma

Papovavirus

Papule

Paracoccidioidomycosis

Parainfluenza viruses

Paraneoplastic syndromes

Paraphilia

Parasitology

Parasomnia

Parasympathetic nervous system

Parathyroid adenomas

Parathyroid glands

Parathyroid hormone (PTH)

Parkinson disease

Paroxetine

Paroxysmal nocturnal hemoglobinuria

Parvovirus

Pasteurella

Patch

Patent ductus arteriosus (PDA)

Pathologic grief

PCAM. See Platelet cell adhesion molecule

PCP. See Phencyclidine hydrochloride

PDA. See Patent ductus arteriosus

Pectinate line

Pediatric disorders, of gastrointestinal system

Pellagra

Pelvic inflammatory disease (PID)

Pemphigus vulgaris

Penicillamine

Penicillin

Penile neoplasm

Pentamidine

Pentose phosphate pathway

Pepsinogen

Peptic ulcer disease

Peptidoglycan

Pericarditis

Pericardium

Peripheral blood smear

Permeability

Perphenazine

Personality disorders

Peutz-Jeghers syndrome

Peyer patches

Peyronie disease

p53

P–450

Pharmacodynamics

Pharmacology. See also specific drugs

basic

cardiovascular system

endocrine system

gastrointestinal system

genitourinary system

nervous system

for psychiatric disorders

respiratory system

Pharyngitis

Phencyclidine hydrochloride (PCP)

Phenelzine

Phenobarbital

Phenoxybenzamine

Phentolamine

Phenylalanine

Phenylephrine

Phenylketonuria

Phenytoin

Pheochromocytoma

Phobia

Phrenic nerve

Physical child abuse

Physiology

cardiovascular system

endocrine system

gastrointestinal system

genitourinary system

musculoskeletal system

reproductive system

respiratory system

sleep

Physostigmine

Pick disease

Picornaviruses

PID. See Pelvic inflammatory disease

Pigments

Pilocarpine

Pindolol

Pinworm infection

Pioglitazone

Piperacillin

Pituitary adenoma

Pituitary gland

Pituitary tumor

Placenta accreta

Placenta previa

Plaque

Platelet aggregation

Platelet cell adhesion molecule (PCAM)

Pleomorphic adenoma

Pleural effusion

Pneumocystis

Pneumonia

Poliomyelitis

Poliovirus

Polycystic kidney disease

Polycystic ovarian syndrome

Polycythemia vera

Polymyalgia rheumatica

Polymyositis

Polymyxins

Pontiac fever

Porta hepatis

Portal-systemic shunt

Port-wine stain birthmark

Posaconazole

Positive predictive value

Posterior pituitary

Posttraumatic stress disorder (PTSD)

Potassium iodide

Potency

Pott disease

Potter syndrome

Poxviridae

PPD test. See Purified protein derivative test

PR interval

Pralidoxime

Praziquantel

Prazosin

Precision

Precocious puberty

Prednisone

Preeclampsia

Pregnancy

Presbycusis

Prevalence

Priapism

Primaquine

Primary biliary cirrhosis

Prions

Probenecid

Procainamide

Procaine

Progesterone

Progressive multifocal leukoencephalopathy

Prolactin

Prolactinoma

Propafenone

Propofol

Propranolol

Propylthiouracil

Prostaglandins

Prostate cancer

Prostate gland

Prostatic carcinoma

Prostatitis

Protamine sulfate

Protease inhibitors

Protein(s)

digestion of

metabolism

Proteus

Protozoa

P-selectin

Pseudogout

Pseudohyperparathyroidism

Pseudohypoparathyroidism

Pseudomembranous colitis

Pseudomonas

Psittacosis

Psoriasis

Psychiatric disorders

childhood

mood

personality

psychopharmacology

psychoses

somatoform

Psychiatry

Psychoanalysis

Psychology

Psychopharmacology

Psychoses

PTH. See Parathyroid hormone

PTSD. See Posttraumatic stress disorder

Public health

Pulmonary edema

Pulmonary embolism

Pulmonary fibrosis

Pulmonary infections

Pulmonary thrombus

Pulmonic stenosis

Pulse pressure

Pulvinar

Pupillary dilation

Purified protein derivative (PPD) test

Purkinje system

Pustule

Pyelonephritis

Pyloric stenosis

Pylorus

Pyogenic osteomyelitis

Pyrantel pamoate

Pyridostigmine

Pyridoxine

Pyrimethamine

Pyruvate dehydrogenase deficiency

Q

Q fever

QRS complex

Quetiapine

Quinidine

Quinine

Quinolones

R

RA. See Rheumatoid arthritis

Rabies

Rabies virus

Radiation

Radioimmunoassay (RIA)

Raloxifene

Ranitidine

Rapidly progressive glomerulonephritis (RPGN)

RAS. See Renal artery stenosis

Raynaud disease

RBF. See Renal blood flow

RDS. See Neonatal respiratory distress syndrome (RDS)

Reactive arthritis

Reactive oxygen species

Reassortment

Receptive relaxation

Recombination

Red blood cell production

Regression

Reiter syndrome

Reliability

REM sleep

Renal agenesis

Renal artery stenosis (RAS)

Renal blood flow (RBF)

Renal cell carcinoma

Renal crisis

Renal dysgenesis

Renal failure

Renal infarct

Renal infections

Renal papillary necrosis

Renal stones

Renal tubular acidosis (RTA)

Renal tumors

Renal vascular disease

Renin-angiotensin-aldosterone system

Reoviruses

Reproductive system

anatomy

disorders

breast

case presentations

female

male

embryology

physiology

pregnancy and

Reserpine

Respiration, neurologic regulation of

Respiratory syncytial virus (RSV)

Respiratory system

anatomy

disorders

ARDS

case presentations

cystic fibrosis

lung cancer

neonatal RDS

obstructive lung disease

other pathology

pulmonary edema

pulmonary embolism

pulmonary infections

restrictive lung disease

embryology

pharmacology

physiology

Restriction fragment length polymorphism analysis

Restrictive cardiomyopathy

Restrictive lung disease

Retinol

Retrovirus

Rett syndrome

Reye syndrome

Rh incompatibility

Rheumatic fever

Rheumatic heart disease

Rheumatoid arthritis (RA)

Rhinoviruses

Rhizopus sp.

RIA. See Radioimmunoassay

Ribavirin

Riboflavin

Rickets

Rickettsia

Rifampin

Rimantadine

Risedronate

Risperidone

Ritodrine

Ritonavir

RNA

Rocky Mountain spotted fever

Rods

Rooting reflex

Rose gardener disease

Rosiglitazone

Rotavirus

Roth spots

Rotor syndrome

RPGN. See Rapidly progressive glomerulonephritis

RSV. See Respiratory syncytial virus

RTA. See Renal tubular acidosis

Rubella virus

Rubeola. See Measles virus

Ruffini corpuscle

S

SA node. See Sinoatrial node

Salicylates. See Aspirin

Salicylic acid

Saliva

Salivary glands

Salmonella

San Joaquin fever

Saquinavir

Sarcoidosis

Sarcoma botryoides

Scalded skin syndrome

Scar formation

Scarlet fever

Schistosoma

Schizoaffective disorder

Schizoid personality disorders

Schizophrenia

Schizophreniform disorder

Schizotypal personality disorders

Schwannoma

Sciatica

Scleroderma

Sclerosing retroperitonitis

Scoliosis

Screening tools

Scurvy

Second messengers

Secretin

Seizures

Selegiline

Selenium sulfide

SEM. See Standard error of the mean

Sensory fibers

Septic shock

Seronegative spondyloarthropathies

Serotonin

Sertraline

Severe combined immunodeficiency

Sex hormones

Sexual child abuse

Sexual response cycle

Sexuality

Sézary syndrome

Shaken baby syndrome

Shared psychotic disorder

Sheehan syndrome

Shigella dysenteriae

Shock

Shy-Drager syndrome

SIADH. See Syndrome of inappropriate antidiuretic hormone

Sildenafil

Silicosis

Simmonds disease

Sinoatrial (SA) node

Sjögren syndrome

Skeletal muscle

Skin

anatomy

disorders

embryology

histology

SLE. See Systemic lupus erythematosus

Sleep

Sleep terror disorder

Smooth muscle

SMX. See Sulfamethoxazole

Sodium bicarbonate

Sodium stibogluconate

Somatization disorder

Somatoform disorders

Somatostatin

Sotalol

Southern blot

Specificity

Sperm

Spherocytosis

Sphincter of Oddi

Spider telangiectasia

Spina bifida

Spinal cord disorders

Spinal tracts

Spiral valve

Spironolactone

Spleen

Spongiform encephalopathy

Squamous cell carcinoma

SSRIs

Standard error of the mean (SEM)

Staphylococcus aureus

Staphylococcus epidermidis

Starling equation

Statins

Statistical distributions

Stavudine (d4T)

STDs

Steatorrhea

Steroid hormones

Steroids

Stevens-Johnson syndrome

Stomach

Streptococcus sp.

agalactiae

pneumoniae

pyogenes

viridans

Stretch reflex

Striatal motor system

Stroke

Sturge-Weber syndrome

Subarachnoid space

Subdural hematoma

Subependymal germinal matrix bleed

Submucosal (Meissner) plexus

Suboptimal renal perfusion

Substance abuse

Substance P

Succimer

Succinylcholine

Suicide

Sulfadoxine

Sulfamethoxazole (SMX)

Sulfonamides

Sulfones

Sulfonylureas

Sulfoxone

Superego

Superior vena cava syndrome

Suramin

Surfactant

Sympathetic nervous system

Syncope

Syncytiotrophoblast

Syndrome of inappropriate antidiuretic hormone (SIADH)

Syphilis

Syringomyelia

Systemic lupus erythematosus (SLE)

Systemic sclerosis

Systolic blood pressure

T

T lymphocyte

Tabes dorsalis

Taenia solium

Takayasu arteritis

Tamoxifen

Tamponade

Tardive dyskinesia

Tay-Sachs disease

Tazobactam

TB. See Tuberculosis

TCAs

TEF. See Tracheoesophageal fistula

Teichoic acid

Temporal arteritis

Teniae coli

Teratogens

Terazosin

Terbinafine

Terbutaline

Terfenadine

Testes

Testicular tumors

Testosterone

Tetracaine

Tetracycline

Tetralogy of Fallot

Thalamus

Thalassemia

Thalidomide

T-helper cell

Thenar eminence

Theophylline

Therapeutic index

Thiabendazole

Thiamine

Thiazides

6-thioguanine

Thiopental

Thioridazine

Thiosulfate

Thoracic outlet syndrome

3TC. See Lamivudine

Thrombolytics

Thrombosis

Thrombotic thrombocytopenic purpura (TTP)

Thrush

Thymic aplasia (DiGeorge syndrome)

Thyroid gland

Thyroiditis

Ticlopidine

Tinea corporis

Tinea cruris/capitis/corporis/unguium/pedis

Tinea nigra

Tinea versicolor

Tirofiban

Tissue repair

TMP. See Trimethoprim

TMP-SMX

TNF. See Tumor necrosis factor

Tocainamide

Tolbutamide

Torsion

Tourette syndrome

Toxic megacolon

Toxic shock syndrome

Toxocara canis

Toxoplasma

tPA

Tracheoesophageal fistula (TEF)

Transference reaction

Transient ischemic attack

Transitional cell carcinoma

Transmural infarction

Transplant rejection

Tranylcypromine

Trastuzumab

Trazodone

Trench fever

Triamcinolone

Triamterene

Trichinella spiralis

Trichomonas vaginalis

Trichomoniasis

Trichophyton

Tricuspid regurgitation

Tricyclic antidepressants

Trifluoperazine

Trigeminal neuralgia

Trimethoprim (TMP)

Trisomy 21

Troponin test

Trousseau syndrome

Trypanosoma

Trypsin

t-test

TTP. See Thrombotic thrombocytopenic purpura

Tuberculosis (TB)

Tuberous sclerosis

Tubocurarine

Tubulointerstitial diseases

Tumor markers

Tumor necrosis factor (TNF)

Turcot syndrome

Tylenol. See Acetaminophen

Type I and II errors

Tyramine

Tyrosine

U

UC. See Ulcerative colitis

Ulcerative colitis (UC)

Undulant fever

Urea cycle

Urethritis

Urinary incontinence

Urinary system. See Genitourinary system

Urinary system disorders

Urinary tract infection (UTI)

Urinary tract tumors

Urobilinogen

Urolithiasis

Urothelial carcinoma

Uterine ligaments

Uterus

UTI. See Urinary tract infection

V

Vaccines

Vaginismus

Vaginitis

Vagus nerve

Valacyclovir

Validity

Valproic acid

Valsalva maneuver

Vancomycin

Vardenafil

Variable ratio

Varicella-zoster virus (VZV)

Varicocele

Vascular cell adhesion molecule (VCAM)

Vascular tumors

Vasculitides

Vasoconstriction

Vasodilation

Vasopressin

VATER syndrome

VCAM. See Vascular cell adhesion molecule

Vecuronium

Venlafaxine

Veno-occlusive disease

Ventral spinal artery occlusion

Ventricular septal defect (VSD)

Verapamil

Verruca vulgaris

Vesicle

Vestibular schwannoma

Vestibular system

Vibrio

Vinblastine

Vincristine

Viral hepatitis

Virchow node

Viruses. See also specific viruses

antiviral agents and

infectious diseases

taxonomy

Vitamins

Vitiligo

Volume, lung

Volume of distribution

Volvulus

Von Hippel-Lindau disease

Von Recklinghausen disease

Von Recklinghausen disease of bone

Von Willebrand disease

Voriconazole

VSD. See Ventricular septal defect

VZV. See Varicella-zoster virus

W

Waiter’s tip palsy

Waldenstrom macroglobulinemia

Wallerian degeneration

Warfarin

Waterhouse-Friderichsen syndrome

WBC neoplasms. See White blood cell neoplasms

Wegener granulomatosis

Weil disease

Weil-Felix reaction

Werdnig-Hoffman disease

Wernicke encephalopathy

Wernicke-Korsakoff syndrome

Western blot

Whipple disease

White blood cell (WBC) neoplasms

Wilson disease

Wiskott-Aldrich syndrome

Woolsorter’s disease

Wuchereria bancrofti

X

Xanthoma

Xeroderma pigmentosa

XL agammaglobulinemia. See X-linked agammaglobulinemia

XL recessive disorders. See X-linked recessive disorders

X-linked (XL) agammaglobulinemia

X-linked (XL) recessive disorders

Y

Yaws

Yellow fever virus

Yersinia

Z

Zafirlukast

Zalcitabine (ddC)

Zanamivir

Zenker diverticulum

Zidovudine (AZT)

Zileuton

Zollinger-Ellison syndrome

Содержание

Contributors

Student Reviewers

Preface

Acknowledgments

Chapter 1 BASIC PRINCIPLES

Molecular Biology, Biochemistry, and Genetics

Nutrition

General Embryology

Basic Pathology

Basic Pharmacology

Chapter 2 IMMUNOLOGY

Immunology Basics

Pathology Immune System

Chapter 3 MICROBIOLOGY AND INFECTIOUS DISEASES

Bacteriology

Antibiotics

Virology

Antiviral Agents

Mycology

Antifungals

Parasitology

Chapter 4 NEUROSCIENCE

Embryology

Neuroanatomy and Neurophysiology

Pathology of the Nervous System

Pharmacology of the Nervous System

Chapter 5 CARDIOVASCULAR

Embryology

Anatomy

Physiology

Cardiovascular Pathology and Pathophysiology

Pharmacology

Chapter 6 PULMONARY

Embryology

Anatomy

Physiology

Pathology

Other Pathology

Pharmacology

Chapter 7 GASTROENTEROLOGY

Embryology

Anatomy

Physiology

Pathology

Pharmacology

Chapter 8 REPRODUCTION AND ENDOCRINOLOGY

Embryology

Anatomy

Physiology

Pathology

Pharmacology

Chapter 9 RENAL AND GENITOURINARY

Embryology

Anatomy

Physiology

Functional Regions of the Nephron

Endocrine Functions of the Kidney

Pathology

Pharmacology—Renal

Chapter 10 HEMATOLOGY AND ONCOLOGY

Embryology

Pathology

Pharmacology

Chapter 11 SKIN AND CONNECTIVE TISSUES

Embryology/Anatomy/Histology

Pathology

Chapter 12 MUSCULOSKELETAL

Anatomy

Physiology

Musculoskeletal and Connective Tissue Pathology

Chapter 13 BEHAVIORAL SCIENCES

Life Cycle

Physiology

Substance Abuse

Psychology

Psychiatry

Pharmacology—Psychopharmacology

Medical Ethics

Biostatistics

Public Health/Epidemiology

Chapter 14 MAKE THE DIAGNOSIS

Nutrition

Microbiology and Infectious Diseases

Neuroscience

Cardiovascular

Pulmonary

Gastroenterology

Reproductive/Endocrine

Renal and Genitourinary

Hematology/Oncology

Skin and Connective Tissues

Musculoskeletal

Behavioral Science

Appendix ABBREVIATIONS

Index