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U SM LE ® STEP 1 Lecture Notes 2018 Anatomy Behavioral Science and Social Sciences Biochemistry and Medical Genetics Immunology and Microbiology Pathology Pharmacology Physiology USMLE® is a joint program of the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME), neither of which sponsors or endorses this product. USMLE Step 1 ® LECTURE NOTES USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners. Copyright © 2018 Kaplan, Inc. ISBN: 978-1-5062-2838-9 All rights reserved. No part of this book may be reproduced in any form, by photostat, microfilm, xerography, or any other means, or incorporated into any information retrieval system, electronic or mechanical, without the written permission of Kaplan, Inc. This book may not be duplicated or sold. USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners. USMLETM* STEP 1 ANATOMY USMLETM* STEP 1 BEHAVIORAL SCIENCE USMLETM* STEP 1 BIOCHEMISTRY AND MEDICAL GENETICS USMLETM* STEP 1 IMMUNOLOGY AND MICROBIOLOGY USMLETM* STEP 1 PATHOLOGY USMLETM* STEP 1 PHARMACOLOGY USMLETM* STEP 1 PHYSIOLOGY USMLE ® USMLE Step 1 Anatomy.indb 1 STEP 1 Lecture Notes 2018 Anatomy 9/15/17 10:50 AM USMLE® is a joint program of the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME), neither of which sponsors or endorses this product. This publication is designed to provide accurate information in regard to the subject matter covered as of its publication date, with the understanding that knowledge and best practice constantly evolve. The publisher is not engaged in rendering medical, legal, accounting, or other professional service. If medical or legal advice or other expert assistance is required, the services of a competent professional should be sought. This publication is not intended for use in clinical practice or the; delivery of medical care. To the fullest extent of the law, neither the Publisher nor the Editors assume any liability for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this book. © 2018 by Kaplan, Inc. Published by Kaplan Medical, a division of Kaplan, Inc. 750 Third Avenue New York, NY 10017 10 9 8 7 6 5 4 3 2 1 Course ISBN: 978-1-5062-2823-5 All rights reserved. The text of this publication, or any part thereof, may not be reproduced in any manner whatsoever without written permission from the publisher. This book may not be duplicated or resold, pursuant to the terms of your Kaplan Enrollment Agreement. Retail ISBN: 978-1-5062-3952-1 Kaplan Publishing print books are available at special quantity discounts to use for sales promotions, employee premiums, or educational purposes. For more information or to purchase books, please call the Simon & Schuster special sales department at 866-506-1949. USMLE Step 1 Anatomy.indb 2 9/15/17 10:50 AM Editors James White, PhD Assistant Professor of Cell Biology School of Osteopathic Medicine Rowan University Stratford, NJ Adjunct Assistant Professor of Cell and Developmental Biology University of Pennsylvania School of Medicine Philadelphia, PA David Seiden, PhD Professor of Neuroscience and Cell Biology Rutgers–Robert Wood Johnson Medical School Piscataway, NJ USMLE Step 1 Anatomy.indb 3 9/15/17 10:50 AM We want to hear what you think. What do you like or not like about the Notes? Please email us at firstname.lastname@example.org. USMLE Step 1 Anatomy.indb 4 9/15/17 10:50 AM Table of Contents Part I: Early Embryology and Histology: Epithelia Chapter 1: Gonad Development ����������������������������������������������������������������������3 Chapter 2: First 8 Weeks of Development ������������������������������������������������������7 Chapter 3: Histology: Epithelia������������������������������������������������������������������������13 Part II: Gross Anatomy Chapter 1: Back and Autonomic Nervous System����������������������������������������27 Chapter 2: Thorax��������������������������������������������������������������������������������������������41 Chapter 3: Abdomen, Pelvis, and Perineum������������������������������������������������� 93 Chapter 4: Upper Limb����������������������������������������������������������������������������������187 Chapter 5: Lower Limb��������������������������������������������������������������������������������� 203 Chapter 6: Head and Neck���������������������������������������������������������������������������� 215 Part III: Neuroscience Chapter 1: Nervous System Organization and Development������������������� 235 Chapter 2: Histology of the Nervous System ��������������������������������������������� 245 Chapter 3: Ventricular System����������������������������������������������������������������������257 Chapter 4: The Spinal Cord������������������������������������������������������������������������� 263 Chapter 5: The Brain Stem����������������������������������������������������������������������������287 Chapter 6: The Cerebellum ��������������������������������������������������������������������������321 Chapter 7: Basal Ganglia ����������������������������������������������������������������������������� 329 v USMLE Step 1 Anatomy.indb 5 9/15/17 10:50 AM Chapter 8: Visual Pathways��������������������������������������������������������������������������� 337 Chapter 9: Diencephalon������������������������������������������������������������������������������� 347 Chapter 10: Cerebral Cortex������������������������������������������������������������������������� 353 Chapter 11: Limbic System ����������������������������������������������������������������������������371 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377 Additional resources available at www.kaptest.com/usmlebookresources vi USMLE Step 1 Anatomy.indb 6 9/15/17 10:50 AM PART I Early Embryology and Histology: Epithelia USMLE Step 1 Anatomy.indb 1 9/15/17 10:50 AM USMLE Step 1 Anatomy.indb 2 9/15/17 10:50 AM Gonad Development 1 Learning Objectives ❏❏ Explain information related to indifferent gonad ❏❏ Interpret scenarios on testis and ovary ❏❏ Answer questions about meiosis ❏❏ Interpret scenarios on spermatogenesis ❏❏ Solve problems concerning oogenesis INDIFFERENT GONAD Although sex is determined at fertilization, the gonads initially go through an indifferent stage weeks 4–7 when there are no specific ovarian or testicular characteristics. The indifferent gonads develop in a longitudinal elevation or ridge of intermediate mesoderm called the urogenital ridge. The components of the indifferent gonads are as follows: • Primordial germ cells provide a critical inductive influence on gonad development, migrating in at week 4. They arise from the lining cells in the wall of the yolk sac. • Primary sex cords are finger-like extensions of the surface epithe- lium which grow into the gonad that are populated by the migrating primordial germ cells. • Mesonephric (Wolffian) and the paramesonephric (Mullerian) ducts of the indifferent gonad contribute to the male and female genital tracts, respectively. TESTIS AND OVARY The indifferent gonad develops into either the testis or ovary. Development of the testis and male reproductive system is directed by the following: • Sry gene on the short arm of the Y chromosome, which encodes for testis-determining factor (TDF) • Testosterone, which is secreted by the Leydig cells • Müllerian-inhibiting factor (MIF), which is secreted by the Sertoli cells • Dihydrotestosterone (DHT): external genitalia 3 USMLE Step 1 Anatomy.indb 3 9/15/17 10:50 AM Part I l Early Embryology and Histology: Epithelia Anatomy Immunology Pharmacology Biochemistry Development of the ovary and female reproductive system requires estrogen. Ovarian development occurs in the absence of the Sry gene and in the presence of the WNT4 gene. MIF: Müllerian-inhibiting factor TDF: testis-determining factor Physiology Primordial germ cells Medical Genetics Yolk sac Pathology Behavioral Science/Social Sciences Urogenital ridge Mesonephric duct (Wolffian) MIF: Müllerian-inhibiting factor TDF: testis-determining factor Paramesonephric duct (Müllerian) Microbiology Indifferent gonad TDF Testosterone MIF No factors Testis and male genital system Ovary and female genital system Figure I-1-1. Development of Testis and Ovary Figure I-1-1. Development of Testis and Ovary MEIOSIS Meiosis occurs within the testis and ovary. This is a specialized process of cell division that produces the male gamete (spermatogenesis) and female gamete (oogenesis). There are notable differences between spermatogenesis and oogenesis. Meiosis consists of 2 cell divisions. In meiosis I, the following events occur: • Synapsis: pairing of 46 homologous chromosomes • Crossing over: exchange of segments of DNA • Disjunction: separation of 46 homologous chromosome pairs (no centromere-splitting) into 2 daughter cells, each containing 23 chromosome pairs In meiosis II, synapsis does not occur, nor does crossing over. Disjunction does occur with centromere-splitting. 4 USMLE Step 1 Anatomy.indb 4 9/15/17 10:50 AM Chapter 1 Type B Spermatogonia Oogonia l Gonad Development (46, 2n) (Diploid) Meiosis I Primary spermatocyte DNA replication (46, 4n) Primary oocyte Synapsis Crossover Cell division Alignment and disjunction Centromeres do not split Secondary spermatocyte Secondary oocyte (23, 2n) Meiosis II Cell division Alignment and disjunction Centromeres split Gamete (23, 1n) (Haploid) Figure I-1-2. Meiosis Figure I-1-2. Meiosis 5 USMLE Step 1 Anatomy.indb 5 9/15/17 10:50 AM Part I Anatomy Pharmacology l Early Embryology and Histology: Epithelia Immunology Biochemistry SPERMATOGENESIS At week 4, primordial germ cells arrive in the indifferent gonad and remain dormant until puberty. • When a boy reaches puberty, primordial germ cells differentiate into type A spermatogonia, which serve as stem cells throughout adult life. • Some type A spermatogonia differentiate into type B spermatogonia. Physiology Medical Genetics • Type B spermatogonia enter meiosis I to form primary spermatocytes. • Primary spermatocytes form 2 secondary spermatocytes. • Secondary spermatocytes enter meiosis II to form 2 spermatids. Pathology Microbiology Behavioral Science/Social Sciences • Spermatids undergo spermiogenesis, which is a series of morphologi- cal changes resulting in the mature spermatozoa. OOGENESIS At week 4, primordial germ cells arrive in the indifferent gonad and differentiate into oogonia. Oogonia enter meiosis I to form primary oocytes. All primary oocytes are formed by month 5 of fetal life; they are arrested the first time in prophase (diplotene) of meiosis I and remain arrested until puberty. • Primary oocytes arrested in meiosis I are present at birth. • When a girl reaches puberty, during each monthly cycle a primary oocyte becomes unarrested and completes meiosis I to form a secondary oocyte and polar body. • The secondary oocyte becomes arrested the second time in meta- phase of meiosis II and is ovulated. • At fertilization within the uterine tube, the secondary oocyte com- pletes meiosis II to form a mature oocyte and polar body. 6 USMLE Step 1 Anatomy.indb 6 9/15/17 10:50 AM First 8 Weeks of Development 2 Learning Objectives ❏❏ Solve problems concerning beginning of development I ❏❏ Demonstrate understanding of the formation of the bilaminar embryo ❏❏ Solve problems concerning embryonic period WEEK 1: BEGINNING OF DEVELOPMENT Fertilization occurs in the ampulla of the uterine tube when the male and female pronuclei fuse to form a zygote. At fertilization, the secondary oocyte rapidly completes meiosis II. sis mito : e g va ea l C Day 2 2-cell Blastula Day 3 Embryoblast (forms embryo) 4-cell Blastula Day 4 Morula Trophoblast (forms placenta) Day 5 (46, 2N) Zygote Blastocyst Day 1 Day 6 (Implantation begins) Fertilization Ovary Zona pellucida Corona radiata cells Secondary oocyte arrested in metaphase of meiosis II Ampulla of oviduct Cytotrophoblast Blastocyst cavity Embryoblast Syncytiotrophoblast FigureFigure I-2-1. Week I-2-1.1Week 1 7 USMLE Step 1 Anatomy.indb 7 9/15/17 10:50 AM Part I Anatomy l Early Embryology and Histology: Epithelia Immunology Prior to fertilization, spermatozoa undergo 2 changes in the female genital tract: • Capacitation consists of the removal of several proteins from the Pharmacology Biochemistry plasma membrane of the acrosome of the spermatozoa. It occurs over about 7 hours in the female reproductive tract. • Hydrolytic enzymes are released from the acrosome used by the sperm Physiology Pathology Medical Genetics Behavioral Science/Social Sciences to penetrate the zona pellucida. This results in a cortical reaction that prevents other spermatozoa penetrating the zona pellucida thus preventing polyspermy. During the first 4–5 days of week 1, the zygote undergoes rapid mitotic division (cleavage) in the oviduct to form a blastula, consisting of increasingly smaller blastomeres. This becomes the morula (32-cell stage). A blastocyst forms as fluid develops in the morula. The blastocyst consists of an inner cell mass known as the embryoblast, and the outer cell mass known as the trophoblast, which becomes the placenta. Microbiology At the end of week 1, the trophoblast differentiates into the cytotrophoblast and syncytiotrophoblast and then implantation begins. Clinical Correlate Ectopic Pregnancy Tubal (most common form) usually occurs when the blastocyst implants within the ampulla of the uterine tube because of delayed transport. Risk factors include endometriosis, pelvic inflammatory disease, tubular pelvic surgery, and exposure to diethylstilbestrol (DES.) Clinical signs include abnormal or brisk uterine bleeding, sudden onset of abdominal pain that may be confused with appendicitis, missed menstrual period (e.g., LMP 60 days ago), positive human chorionic gonadotropin test, culdocentesis showing intraperitoneal blood, and positive sonogram. Abdominal form usually occurs in the rectouterine pouch (pouch of Douglas). Implantation For implantation to occur, the zona pellucida must degenerate. The blastocyst usually implants within the posterior wall of the uterus. The embryonic pole of blastocyst implants first. The blastocyst implants within the functional layer of the endometrium during the progestational phase of the menstrual cycle. WEEK 2: FORMATION OF THE BILAMINAR EMBRYO In week 2, the embryoblast differentiates into the epiblast and hypoblast, forming a bilaminar embryonic disk. The epiblast forms the amniotic cavity and hypoblast cells migrate to form the primary yolk sac. The prechordal plate, formed from fusion of epiblast and hypoblast cells, is the site of the future mouth. 8 USMLE Step 1 Anatomy.indb 8 9/15/17 10:50 AM Chapter 2 Hypoblast Epiblast l First 8 Weeks of Development Bilaminar disk Endometrial blood vessel Lacuna spaces Endometrial gland Syncytiotrophoblast • Implantation • hCG Prechordal plate Chorionic cavity Yolk sac Connecting stalk Amniotic cavity Primary villi Chorion Extraembryonic mesoderm Cytotrophoblast FigureI-3-1. I-2-2.Week Week22 Figure Extraembryonic mesoderm is derived from the epiblast. Extraembryonic somatic mesoderm lines the cytotrophoblast, forms the connecting stalk, and covers the amnion. Extraembryonic visceral mesoderm covers the yolk sac. The connecting stalk suspends the conceptus within the chorionic cavity. The wall of the chorionic cavity is called the chorion, consisting of extraembryonic somatic mesoderm, the cytotrophoblast, and the syncytiotrophoblast. The syncytiotrophoblast continues its growth into the endometrium to make contact with endometrial blood vessels and glands. No mitosis occurs in the syncytiotrophoblast. The cytotrophoblast is mitotically active. Hematopoiesis occurs initially in the mesoderm surrounding the yolk sac (up to 6 weeks) and later in the fetal liver, spleen, thymus (6 weeks to third trimester), and bone marrow. 9 USMLE Step 1 Anatomy.indb 9 9/15/17 10:50 AM Part I Anatomy Pharmacology l Early Embryology and Histology: Epithelia Immunology Biochemistry Clinical Correlate Human chorionic gonadotropin (hCG), a glycoprotein produced by the syncytiotrophoblast, stimulates progesterone production by the corpus luteum. hCG can be assayed in maternal blood or urine and is the basis for early pregnancy testing. hCG is detectable throughout pregnancy. • Low hCG level may predict a spontaneous abortion or ectopic pregnancy. Physiology Medical Genetics Pathology Behavioral Science/Social Sciences • H igh hCG level may predict a multiple pregnancy, hydatidiform mole, or gestational trophoblastic disease. WEEKS 3–8: EMBRYONIC PERIOD Microbiology All major organ systems begin to develop during the weeks 3–8. By the end of this period, the embryo begins to look human, and the nervous and cardiovascular systems start to develop. Week 3 corresponds to the first missed menstrual period. Dorsal View Cranial Prechordal plate Primitive node Primitive pit B Primitive streak Cloacal membrane Caudal A Sectional View Cranial Primitive node & streak Epiblast (ectoderm) Amnion Notochord Yolk sac Mesoderm B Endoderm Hypoblast Figure 3 I-2-3. Week 3 Figure I-4-1. Week 10 USMLE Step 1 Anatomy.indb 10 9/15/17 10:50 AM Chapter 2 l First 8 Weeks of Development During this time gastrulation also takes place; this is the process by which the 3 primary germ layers are produced: ectoderm, mesoderm, and endoderm. It begins with the formation of the primitive streak within the epiblast. • Ectoderm forms neuroectoderm and neural crest cells. • Mesoderm forms paraxial mesoderm (35 pairs of somites), intermedi- ate mesoderm, and lateral mesoderm. Clinical Correlate Sacrococcygeal teratoma: a tumor that arises from remnants of the primitive streak; often contains various types of tissue (bone, nerve, hair, etc) Chordoma: a tumor that arises from remnants of the notochord, found either intracranially or in the sacral region Hydatidiform mole: results from the partial or complete replacement of the trophoblast by dilated villi • In a complete mole, there is no embryo; a haploid sperm fertilizes a blighted ovum and reduplicates so that the karyotype is 46,XX, with all chromosomes of paternal origin. In a partial mole, there is a haploid set of maternal chromosomes and usually 2 sets of paternal chromosomes so that the typical karyotype is 69,XXY. • Molar pregnancies have high levels of hCG, and 20% develop into a malignant trophoblastic disease, including choriocarcinoma. 11 USMLE Step 1 Anatomy.indb 11 9/15/17 10:50 AM Part I Anatomy Early Embryology and Histology: Epithelia l Immunology Table I-2-1. Germ Layer Derivatives Ectoderm Muscle Surface ectoderm Pharmacology Physiology Pathology Biochemistry Epidermis Smooth Hair Cardiac Nails Skeletal Endoderm Forms epithelial lining of: GI track: foregut, midgut, and hindgut Lower respiratory system: larynx, trachea, bronchi, and lung Inner ear, external ear Medical Genetics Connective tissue Enamel of teeth All serous membranes Genitourinary system: urinary bladder, urethra, and lower vagina Lens of eye Bone and cartilage Pharyngeal pouches: Anterior pituitary (Rathke’s pouch) Blood, lymph, cardiovascular organs Parotid gland Behavioral Science/Social Sciences Anal canal below pectinate line Microbiology Mesoderm Neuroectoderm Neural tube Adrenal cortex Gonads and internal reproductive organs Spleen Kidney and ureter • Auditory tube and middle ear • Palatine tonsils • Parathyroid glands • Thymus Forms parenchyma of: Central nervous system Dura mater • Liver Retina and optic nerve Notochord • Pancreas Pineal gland Neurohypophysis Astrocytes Nucleus pulposus • Submandibular and sublingual glands • Follicles of thyroid gland Oligodendrocytes Neural crest ectoderm Adrenal medulla Ganglia Sensory—Pseudounipolar Neurons Autonomic—Postganglionic Neurons Pigment cells Schwann cells Meninges Pia and arachnoid mater Pharyngeal arch cartilage Odontoblasts Parafollicular (C) cells Aorticopulmonary septum Endocardial cushions Extra embryonic structures Yolk sac derivatives: Primordial germ cells Early blood cells and blood vessels 12 USMLE Step 1 Anatomy.indb 12 9/15/17 10:50 AM Histology: Epithelia 3 Learning Objectives ❏❏ Demonstrate understanding of epithelial cells I ❏❏ Use knowledge of epithelium ❏❏ Interpret scenarios on cytoskeletal elements ❏❏ Explain information related to cell adhesion molecules ❏❏ Answer questions about cell surface specializations Histology is the study of normal tissues. Groups of cells make up tissues, tissues form organs, organs form organ systems, and systems make up the organism. Each organ consists of 4 types of tissue: epithelial, connective, nervous, and muscular. Only certain aspects of epithelia will be reviewed here; other aspects of histology are reviewed elsewhere in this book. EPITHELIAL CELLS Epithelial cells are often polarized: the structure, composition, and function of the apical surface membrane differ from those of the basolateral surfaces. The polarity is established by the presence of tight junctions that separate these 2 regions. Internal organelles are situated symmetrically in the cell. Membrane polarity and tight junctions are essential for the transport functions of epithelia. Many simple epithelia transport substances from one side to the other (kidney epithelia transport salts and sugars; intestinal epithelia transport nutrients, antibodies, etc.). There are 2 basic mechanisms used for these transports: • Transcellular pathway through which larger molecules and a combina- tion of diffusion and pumping in the case of ions that pass through the cell • Paracellular pathway that permits movement between cells Tight junctions regulate the paracellular pathway, because they prevent backflow of transported material and keep basolateral and apical membrane components separate. Epithelial polarity is essential to the proper functioning of epithelial cells; when polarity is disrupted, disease can develop. For example, epithelia lining the trachea, bronchi, intestine, and pancreatic ducts transport chloride from basolateral surface to lumen via pumps in the basolateral surface and channels in 13 USMLE Step 1 Anatomy.indb 13 9/15/17 10:50 AM Part I l Early Embryology and Histology: Epithelia Anatomy Immunology Pharmacology Biochemistry Physiology Medical Genetics the apical surface. The transport provides a driving force for Na by producing electrical polarization of the epithelium. Thus NaCl moves across, and water follows. In cystic fibrosis the apical Cl channels do not open. Failure of water transport results in thickening of the mucous layer covering the epithelia. Transformed cells may lose their polarized organization, and this change can be easily detected by using antibodies against proteins specific for either the apical or basolateral surfaces. Loss of polarity in the distribution of membrane proteins may eventually become useful as an early index of neoplasticity. Epithelia are always lined on the basal side by connective tissue containing blood vessels. Since epithelia are avascular, interstitial tissue fluids provide epithelia with oxygen and nutrients. Pathology Microbiology Behavioral Science/Social Sciences Epithelia modify the 2 compartments that they separate. The epithelial cells may either secrete into or absorb from each compartment, and may selectively transport solutes from one side of the barrier to the other. Epithelia renew themselves continuously, some very rapidly (skin and intestinal linings), some at a slower rate. This means that the tissue contains stem cells that continuously proliferate. The daughter cells resulting from each cell division either remain in the pool of dividing cells or differentiate. The epithelial subtypes are as follows: • Simple cuboidal epithelium (e.g., renal tubules, salivary gland acini) • Simple columnar epithelium (e.g., small intestine) • Simple squamous epithelium (e.g., endothelium, mesothelium, epithe- lium lining the inside of the renal glomerular capsule) • Stratified squamous epithelium: nonkeratinized (e.g., esophagus) and keratinizing (e.g., skin) • Pseudostratified columnar epithelium (e.g., trachea, epididymis) • Transitional epithelium (urothelium) (e.g., ureter and bladder) • Stratified cuboidal epithelium (e.g., salivary gland ducts) EPITHELIUM Hematoxylin-and-Eosin Staining The most common way to stain tissues for viewing in the light microscope is to utilize hematoxylin-and-eosin (H&E) staining. Hematoxylin is a blue dye which stains basophilic substrates that are the acidic cellular components such as DNA and RNA. Hematoxylin stains nuclei blue, and may tint the cytoplasm of cells with extensive mRNA in their cytoplasm. 14 USMLE Step 1 Anatomy.indb 14 9/15/17 10:50 AM Chapter 3 l Histology: Epithelia Copyright Companies. Used with permission. CopyrightMcGraw-Hill McGraw-Hill Companies. Used with permission. Figure tubule simple simple cuboidal cuboidal epithelium epithelium(arrow) (arrow) FigureI-5-1. I-3-1.Kidney Kidney tubule stained stainedwith withH&E, H&E, L-lumen L-lumen Eosin is a pink-to-orange dye which stains acidophilic substrates such as basic components of most proteins. Eosin stains the cytoplasm of most cells and many extracellular proteins, such as collagen, pink. Epithelial Subtypes Simple columnar epithelium is found in the small and large intestine. Copyright McGraw-Hill Companies. Used with permission. Copyright McGraw-Hill Companies. Used with permission. FigureI-3-2. I-5-2.Small SmallIntestine Intestine Simple Columnar Epithelium Figure Simple Columnar Epithelium Enterocytes cells (arrowhead) Enterocytes(arrow), (arrow),Goblet Goblet cells (arrowhead) 15 USMLE Step 1 Anatomy.indb 15 9/15/17 10:50 AM Part I l Early Embryology and Histology: Epithelia Anatomy Immunology Pharmacology Biochemistry Physiology Medical Genetics Pathology Behavioral Science/Social Sciences Simple squamous epithelium forms an endothelium that lines blood vessels, a mesothelium that forms part of a serous membrane or forms the epithelium lining of the inside of the renal glomerular capsule. Microbiology Copyright McGraw-Hill Companies. Used with permission. Copyright McGraw-Hill Companies. Used .with permission. Figure Kidneysimple simplesquamous squamousepithelium epithelium(arrows), (arrows), Figure I-5-3. I-3-3. Kidney simple cuboidal epithelium epithelium (arrowheads) (arrowheads) simple cuboidal Pseudostratified columnar epithelium is found in the nasal cavity, trachea, bronchi, and epididymis. Copyright McGraw-Hill Used permission. Copyright McGraw-HillCompanies. Companies. Usedwith with permission. Figure pseudostratifiedcolumnar columnarepithelium epitheliumwith with FigureI-5-4. I-3-4. Trachea Trachea pseudostratified true cilia (arrow) and goblet cells (arrowhead), basement true cilia (arrow) and goblet cells (arrowhead), basement membrane (curved arrow) arrow) membrane (curved 16 USMLE Step 1 Anatomy.indb 16 9/15/17 10:50 AM Chapter 3 l Histology: Epithelia Transitional epithelium is found in the ureter and bladder. Copyright McGraw-Hill Companies. Used with permission. Copyright McGraw-Hill Companies. Used with permission. Figure I-5-5. Bladder BladderTransitional TransitionalEpithelium Epithelium Figure I-3-5. Stratified squamous epithelium is found in the oral cavity, pharynx, and esophagus (non-keratinized) and in the skin (keratinizing). Copyright McGraw-Hill Used with permission. Copyright McGraw-HillCompanies. Companies. Used with permission. Figure Epithelium(Thick (ThickSkin) Skin) FigureI-5-6. I-3-6.Stratified Stratified Squamous Squamous Epithelium stratumbasale basale(2) (2)stratum stratum spinosum spinosum (3) (1)(1)stratum (3) stratum stratum granulosum granulosum (4)stratum stratum lucidum lucidum (5) (5) stratum stratum corneum (4) corneum Simple cuboidal epithelium is the epithelium of the renal tubules and the secretory cells of salivary gland acini. Stratified cuboidal epithelium is found in the ducts of salivary glands. 17 USMLE Step 1 Anatomy.indb 17 9/15/17 10:50 AM Part I l Early Embryology and Histology: Epithelia Anatomy Immunology Pharmacology Biochemistry Physiology Medical Genetics Pathology Behavioral Science/Social Sciences Copyright McGraw-Hill Companies. Used with permission. Copyright McGraw-Hill Companies. Used with permission. Microbiology FigureI-3-7. I-5-7.Ducts Ducts salivary gland with stratified Figure ofof salivary gland with stratified cuboidalepithelium epitheliumsmall smallblood bloodvessels vessels with cuboidal with endotheliumand andsmooth smoothmuscle muscle(arrows) (arrows) endothelium Glands Unicellular glands are goblet cells found in the respiratory and GI epithelium. Multicellular glands may be exocrine (salivary gland) or endocrine (thyroid gland), but all have tubules or acini formed mainly by a simple cuboidal epithelium. Only exocrine glands have ducts, which serve as conduits for glandular secretions to a body surface or to a lumen. Copyright McGraw-Hill permission. Copyright McGraw-HillCompanies. Companies.Used Usedwith with permission. Figure I-5-8.Submandibular SubmandibularGland gland Figure I-3-8. Mixed salivary glandsalivary with mucous This gland is a mixed glandacini with (arrow) mucus and acinidarker (arrow) staining serous acini; small blood vessels (arrowheads) and darker staining serous acini; small blood vessels (arrowheads) 18 USMLE Step 1 Anatomy.indb 18 9/15/17 10:50 AM Chapter 3 l Histology: Epithelia CYTOSKELETAL ELEMENTS Microfilaments Microfilaments are actin proteins. They are composed of globular monomers of G-actin that polymerize to form helical filaments of F-actin. Actin polymerization is ATP dependent. The F-actin filaments are 7-nm-diameter filaments that are constantly ongoing assembly and disassembly. F-actin has a distinct polarity. The barbed end (the plus end) is the site of polymerization and the pointed end is the site of depolymerization. Tread milling is the balance in the activity at the 2 ends. In conjunction with myosin, actin microfilaments provide contractile and motile forces of cells including the formation of a contractile ring that provides a basis for cytokinesis during mitosis and meiosis. Actin filaments are linked to cell membranes at tight junctions and at the zonula adherens, and form the core of microvilli. Intermediate Filaments Intermediate filaments are 10-nm-diameter filaments that are usually stable once formed. These filaments provide structural stability to cells. There are 4 types: • Type I: keratins (keratins are found in all epithelial cells) • Type II: intermediate filaments comprising a diverse group Clinical Correlate A first step in the invasion of malignant cells through an epithelium results from a loss of expression of cadherins that weakens the epithelium. –– Desmin is found in skeletal, cardiac, and GI tract smooth muscle cells. Clinical Correlate –– Vimentin is found in most fibroblasts, fibrocytes, endothelial cells, and vascular smooth muscle. Changes in intermediate filaments are evident in neurons in Alzheimer’s disease and in cirrhotic liver diseases. –– Glial fibrillary acidic protein is found in astrocytes and some Schwann cells. –– Peripherin is found in peripheral nerve axons. • Type III: intermediate filaments forming neurofilaments in neurons • Type IV: 3 types of lamins forming a meshwork rather than individual filaments inside the nuclear envelope of all cells Microtubules Microtubules consist of 25-nm-diameter hollow tubes. Like actin, microtubules undergo continuous assembly and disassembly. They provide “tracks” for intracellular transport of vesicles and molecules. Such transport exists in all cells but is particularly important in axons. Transport requires specific ATPase motor molecules; dynein drives retrograde transport and kinesin drives anterograde transport. Microtubules are found in true cilia and flagella, and utilize dynein to convey motility to these structures. Microtubules form the mitotic spindle during mitosis and meiosis. Clinical Correlate Colchicine prevents microtubule polymerization and is used to prevent neutrophil migration in gout. Vinblastine and vincristine are used in cancer therapy because they inhibit the formation of the mitotic spindle. 19 USMLE Step 1 Anatomy.indb 19 9/15/17 10:51 AM Part I l Early Embryology and Histology: Epithelia Anatomy Immunology Pharmacology Biochemistry Physiology Medical Genetics Pathology Behavioral Science/Social Sciences CELL ADHESION MOLECULES Cell adhesion molecules are surface molecules that allow cells to adhere to one another or to components of the extracellular matrix. The expression of adhesion molecules on the surface of a given cell may change with time, altering its interaction with adjacent cells or the extracellular matrix. Cadherin and selectin are adhesion molecules that are calcium ion-dependent. The extracellular portion binds to a cadherin dimer on another cell (trans binding). The cytoplasmic portions of cadherins are linked to cytoplasmic actin filaments by the catenin complex of proteins. Integrins are adhesion molecules that are calcium-independent. They are transmembrane surface molecules with extracellular domains that bind to fibronectin and laminin, which are components of extracellular basement membrane. The cytoplasmic portions of integrins bind to actin filaments. Integrins form a portion of hemidesmosomes but are also important in interactions between leukocytes and endothelial cells. Microbiology CELL SURFACE SPECIALIZATIONS Cell Adhesion • Painful flaccid bullae (blisters) in oropharynx and skin that rupture easily A cell must physically interact via cell surface molecules with its external environment, whether it be the extracellular matrix or basement membrane. The basement membrane is a sheet-like structure underlying virtually all epithelia, which consists of basal lamina (made of type IV collagen, glycoproteins [e.g., laminin], and proteoglycans [e.g., heparin sulfate]), and reticular lamina (composed of reticular fibers). Cell junctions anchor cells to each other, seal boundaries between cells, and form channels for direct transport and communication between cells. The 3 types of junctional complex include anchoring, tight, and gap junctions. • Postinflammatory hyperpigmentation Cell Junctions Clinical Correlate Pemphigus Vulgaris • Autoantibodies against desmosomal proteins in skin cells • Treatment: corticosteroids Bullous Pemphigoid • Autoantibodies against basement-membrane hemidesmosomal proteins • Widespread blistering with pruritus • Less severe than pemphigus vulgaris • Rarely affects oral mucosa • Can be drug-induced (e.g., middle-aged or elderly patient on multiple medications) • Treatment: corticosteroids Tight junctions (zonula occludens) function as barriers to diffusion and determine cell polarity. They form a series of punctate contacts of adjacent epithelial cells near the apical end or luminal surface of epithelial cells. The major components of tight junctions are occludens (ZO-1,2,3) and claudin proteins. These proteins span between the adjacent cell membranes and their cytoplasmic parts bind to actin microfilaments. Zonula adherens forms a belt around the entire apicolateral circumference of the cell, immediately below the tight junction of epithelium. Cadherins span between the cell membranes. Like the tight junctions immediately above them, the cytoplasmic parts of cadherins are associated with actin filaments. Desmosomes (macula adherens) function as anchoring junctions. Desmosomes provide a structural and mechanical link between cells. Cadherins span between the cell membranes of desmosomes and internally desmosomes are anchored to intermediate filaments in large bundles called tonofilaments. Hemidesmosomes adhere epithelial cells to the basement membrane. The basement membrane is a structure that consists of the basal membrane of a cell 20 USMLE Step 1 Anatomy.indb 20 9/15/17 10:51 AM Chapter 3 l Histology: Epithelia and 2 underlying extracellular components, the basal lamina and the reticular lamina. The basal lamina is a thin felt-like extracellular layer composed of predominantly of type IV collagen associated with laminin, proteoglycans, and fibronectin that are secreted by epithelial cells. Fibronectin binds to integrins on the cell membrane, and fibronectin and laminin in turn bind to collagen in the basal lamina. Internally, like a desmosome, the hemidesmosomes are linked to intermediate filaments. Below the basal lamina is the reticular lamina, composed of reticular fibers. Through the binding of extracellular components of hemidesmosomes to integrins, and thus to fibronectin and laminin, the cell is attached to the basement membrane and therefore to the extracellular matrix components outside the basement membrane. These interactions between the cell cytoplasm and the extracellular matrix have implications for permeability, cell motility during embryogenesis, and cell invasion by malignant neoplasms. Gap junctions (communicating junctions) function in cell-to-cell communication between the cytoplasm of adjacent cells by providing a passageway for ions such as calcium and small molecules such as cyclic adenosine monophosphate (cAMP). The transcellular channels that make up a gap junction consist of connexons, which are hollow channels spanning the plasma membrane. Each connexon consists of 6 connexin molecules. Unlike other intercellular junctions, gap junctions are not associated with any cytoskeletal filament. Apical surface Microvilli Plasma membrane Tight junction Actin microfilaments Intermediate filaments (keratin) Zonula adherens Desmosome Cell A Cell B Cell C Gap junction Cell D Hemidesmosome Basal lamina Figure I-5-9.Junctions Junctions Figure I-3-9. 21 USMLE Step 1 Anatomy.indb 21 9/15/17 10:51 AM Part I l Early Embryology and Histology: Epithelia Anatomy Immunology Pharmacology Biochemistry Physiology Medical Genetics Pathology Behavioral Science/Social Sciences Sealing strands of tight junction Microbiology Copyright Lippincott Williams & Wilkins. Used with permission. Copyright Lippincott Williams & Wilkins. Used with permission. Figure I-5-10. Freeze-fracture of tight junction Figure I-3-10. Freeze-fracture of Tight Junction Connexon ce spa r a l A cellu of cell a r t r n I e bilay B Lipid cell r of e y bila ce spa Lipid r a l cellu Intra 2–4 nm 1.5 nm 7 nm Figure junction Figure I-5-11. I-3-11. Gap Gap Junction Microvilli Microvilli contain a core of actin microfilaments and function to increase the absorptive surface area of an epithelial cell. They are found in columnar epithelial cells of the small and large intestine, cells of the proximal tubule of the kidney and on columnar epithelial respiratory cells. Stereocilia are long, branched microvilli that are found in the male reproductive tract (e.g., epididymis). Short stereocilia cap all sensory cells in the inner ear. 22 USMLE Step 1 Anatomy.indb 22 9/15/17 10:51 AM Chapter 3 l Histology: Epithelia Glycocalyx Microvilli Zonula occludens (tight junction) Zonula adherens Desmosome Figure I-3-12. Apical CellApical Surface/Cell Junctions junctions Figure I-5-12. cell surface/cell Cilia Clinical Correlate Cilia contain 9 peripheral pairs of microtubules and 2 central microtubules. The microtubules convey motility to cilia through the ATPase dynein. Cilia bend and beat on the cell surface of pseudostratified ciliated columnar respiratory epithelial cells to propel overlying mucous. They also form the core of the flagella, the motile tail of sperm cells. Kartagener syndrome is characterized by immotile spermatozoa and infertility. It is due to an absence of dynein that is required for flagellar motility. It is usually associated with chronic respiratory infections because of similar defects in cilia of respiratory epithelium. B = Basal body B: basal body IJ = Intermediate junction MIJ:=intermediate Microvillus junction OJM:=microvillus Occluding junction OJ: occluding junction Copyright Lippincott & Wilkins. Used withwith permission. Copyright LippincottWilliams Williams & Wilkins. Used permission. Figure I-5-13. Cilia Figure I-3-13. Cilia 23 USMLE Step 1 Anatomy.indb 23 9/15/17 10:51 AM Part I Anatomy l Early Embryology and Histology: Epithelia Immunology B Pharmacology Biochemistry Dynein arms A 1 Spoke Nexin link 2 9 3 Physiology Medical Genetics 8 Central singlet Pathology 4 7 Behavioral Science/Social Sciences 6 Microbiology 5 Plasma membrane Central sheath Bridge Figure of aaCilium cilium FigureI-5-14. I-3-14.Structure Structure of of the the axoneme Axoneme of 24 USMLE Step 1 Anatomy.indb 24 9/15/17 10:51 AM PART II Gross Anatomy USMLE Step 1 Anatomy.indb 25 9/15/17 10:51 AM USMLE Step 1 Anatomy.indb 26 9/15/17 10:51 AM Back and Autonomic Nervous System 1 Learning Objectives ❏❏ Solve problems concerning vertebral column ❏❏ Demonstrate understanding of spinal meninges ❏❏ Use knowledge of spinal nerves ❏❏ Use knowledge of autonomic nervous system VERTEBRAL COLUMN Embryology During week 4, sclerotome cells of the somites (mesoderm) migrate medially to surround the spinal cord and notochord. After proliferation of the caudal portion of the sclerotomes, the vertebrae are formed, each consisting of the caudal part of one sclerotome and the cephalic part of the next. Vertebrae The vertebral column is the central component of the axial skeleton which functions in muscle attachments, movements, and articulations of the head and trunk. • The vertebrae provide a flexible support system that transfers the weight of the body to the lower limbs and also provides protection for the spinal cord. • The vertebral column is composed of 32–33 vertebrae (7 cervical, 12 thoracic, 5 lumbar, and the fused 5 sacral, and 3–4 coccygeal), intervertebral disks, synovial articulations (zygapophyseal joints) and ligaments. 27 USMLE Step 1 Anatomy.indb 27 9/15/17 10:51 AM Part II Gross Anatomy l Anatomy Immunology Pharmacology Biochemistry ~33 vertebrae ~33 vertebrae 31 spinal nerves Physiology 31 spinal nervesMedical Genetics Anterior view Pathology Atlas (C1)Behavioral Science/Social Sciences Axis (C2) Lateral view Posterior view Cervical curvature C7 T1 C7 T1 Microbiology Intervertebral disk Intervertebral foramen T12 L1 Thoracic curvature Cervical vertebrae (7) Thoracic vertebrae (12) T12 L1 Lumbar vertebrae (5) L5 Lumbar curvature L5 Sacrum (S1–5) Coccyx Interlaminar space Sacrum (5) Sacral curvature Sacral hiatus (caudal block) Coccyx Figure II-1-1. Vertebral Column Figure II-1-1. Vertebral Column 28 USMLE Step 1 Anatomy.indb 28 9/15/17 10:51 AM Chapter 1 l Back and Autonomic Nervous System A typical vertebra consists of an anterior body and a posterior vertebral arch consisting of 2 pedicles and 2 laminae. The vertebral arch encloses the vertebral (foramen) canal that houses the spinal cord. Vertebral notches of adjacent pedicles form intervertebral foramina that provide for the exit of the spinal nerves. The dorsal projecting spines and the lateral projecting transverse processes provide attachment sites for muscles and ligaments. Spinous process Lamina Transverse process Vertebral foramen Pedicle Body A Facet on superior articular process Pedicle Body Inferior vertebral notch B Spinous process Superior and inferior articular processes Figure II-1-2. Typical Vertebra Figure II-1-2. Typical Vertebra Intervertebral Disks The intervertebral disks contribute to about 25% of the length of the vertebral column. They form the cartilaginous joints between the vertebral bodies and provide limited movements between the individual vertebrae. • Each intervertebral disk is numbered by the vertebral body above the disk. • Each intervertebral disk is composed of the following: –– Anulus fibrosus consists of the outer concentric rings of fibrocartilage and fibrous connective tissue. The anuli connect the adjacent bodies and provide limited movement between the individual vertebrae. –– Nucleus pulposus is an inner soft, elastic, compressible material that functions as a shock absorber for external forces placed on the vertebral column. The nucleus pulposus is the postnatal remnant of the notochord. 29 USMLE Step 1 Anatomy.indb 29 9/15/17 10:51 AM Part II l Gross Anatomy Anatomy Immunology Intervertebral disk Intervertebral foramen Biochemistry Ventral Pharmacology Pedicle Anterior longitudinal ligament Physiology Medical Genetics Annulus fibrosus Pathology Nucleus pulposus L4 Spinal nerve Behavioral Science/Social Sciences Posterolateral herniation Posterior longitudinal ligament Posterior longitudinal ligament Microbiology Dorsal A. Intervertebral Disk Zygapophyseal joint Anterior longitudinal ligament B. Intervertebral Foramen Figure II-1-3. Intervertebral Disks Figure II-1-3. Intervertebral Disks Clinical Correlate Ligaments of the Vertebral Column The herniation of a nucleus pulposus is most commonly in a posterolateral direction due to the strength and position of the posterior longitudinal ligament (Figure II-1-3-A). The vertebral bodies are strongly supported by 2 longitudinal ligaments. Both ligaments are firmly attached to the intervertebral disks and to the bodies of the vertebrae. • Anterior longitudinal ligament forms a broad band of fibers that connects the anterior surfaces of the bodies of the vertebrae between the cervical and sacral regions. It prevents hyperextension of the vertebrae and is often involved in “whiplash” accidents. • Posterior longitudinal ligament connects the posterior surfaces of the vertebral bodies and is located in the vertebral canal. It limits flexion of the vertebral column. This ligament causes the herniation of a disk to be positioned posterolaterally. 30 USMLE Step 1 Anatomy.indb 30 9/15/17 10:51 AM Chapter 1 l Back and Autonomic Nervous System Herniated Disk The nucleus pulposus may herniate through the anulus fibrosus. The herniated nucleus pulposus may compress the spinal nerve roots, resulting in pain along the involved spinal nerve (sciatica). • Herniation usually occurs in the lower lumbar (L4/L5 or L5/S1) or lower cervical (C5/C6 or C6/C7) parts of the vertebral column. • The herniated disk will usually compress the spinal nerve roots one number below the involved disk (e.g., the herniation of the L4 disk will compress the L5 roots, or herniation of the C7 disk will compress the C8 nerve roots). 4th lumbar spinal nerve Nucleus pulposus L4 Herniation of the L4 nucleus pulposus into vertebral canal Compresses roots of 5th lumbar spinal nerve L5 S1 Herniated Intervertebral FigureFigure II-1-4.II-1-4. Herniated Intervertebral DiskDisk Intervertebral Foramen The intervertebral foramina are formed by successive intervertebral notches and provide for the passage of the spinal nerve. The boundaries of the foramina are: • Anterior: bodies of the vertebrae and intervertebral disks • Posterior: zygapophyseal joint and articular processes • Superior and inferior: pedicles of the vertebrae SPINAL MENINGES The spinal cord is protected and covered by 3 connective tissue layers within the vertebral canal: the dura mater, arachnoid, and pia mater. 31 USMLE Step 1 Anatomy.indb 31 9/15/17 10:51 AM Part II Anatomy l Gross Anatomy Immunology Epidural space Vertebral body Pia mater Pharmacology Biochemistry Epidural fat Arachnoid mater Dura mater Subarachnoid space Ventral root of spinal nerve Physiology Medical Genetics Pathology Behavioral Science/Social Sciences Spinal nerve Dorsal root of spinal nerve Intervertebral foramen Denticulate ligament Microbiology Internal vertebral venous plexus Figure II-1-5. of Vertebral Canal Figure II-1-5.Cross-Section Cross-Section of Vertebral Canal Dura Mater The dura mater is a tough, cylindrical covering of connective tissue forming a dural sac which envelops the entire spinal cord and cauda equina. • The dura mater and dural sac terminate inferiorly at the second sacral vertebra level. • Superiorly, the dura mater continues through the foramen magnum and is continuous with the meningeal layer of the cranial dura. Arachnoid The arachnoid is a delicate membrane which completely lines the inner surface of the dura mater and dural sac. It continues inferiorly and terminates at the second sacral vertebra. Pia Mater The pia mater is tightly attached to the surface of the spinal cord and provides a delicate covering of the cord. • The spinal cord, with its covering of pia mater, terminates at the L1 or L2 vertebral levels in the adult. • There are 2 specializations of the pia mater that are attached to the spinal cord: –– The denticulate ligaments are bilateral thickenings of pia mater that run continuously on the lateral sides of the midpoint of the cord. They separate the ventral and dorsal roots of the spinal nerves and anchor to the dura mater. 32 USMLE Step 1 Anatomy.indb 32 9/15/17 10:51 AM Chapter 1 Back and Autonomic Nervous System l –– The filum terminale is a continuation of the pia mater distal to the lower end of the spinal cord. The filum terminale is part of the cauda equina which is composed of ventral and dorsal roots of lumbar and sacral nerves that extend below the inferior limit of the spinal cord. There are 2 spaces related to the meninges. The epidural space is located between the inner walls of the vertebral canal and the dura mater. It contains fat and the internal vertebral venous plexus. The venous plexus runs the entire length of the epidural space and continues superiorly through the foramen magnum to connect with dural venous sinuses in the cranial cavity. The subarachnoid space is a pressurized space located between the arachnoid and pia mater layers. It contains cerebrospinal fluid (CSF), which bathes the spinal cord and spinal nerve roots within the dural sac, and terminates at the second sacral vertebral level. Clinical Correlate The internal vertebral venous plexus is valveless and connects with veins of the pelvis, abdomen, and thorax. It provides a route of metastasis of cancer cells to the vertebral column and the cranial cavity. There are 2 important vertebral levels. The L1 or L2 vertebrae is the inferior limit of the spinal cord in adults (conus medullaris). S2 vertebra is the inferior limit of the dural sac and the subarachnoid space (cerebrospinal fluid). Thoracic vertebrae L2 vertebra Lumbar vertebrae S2 vertebra Sacrum A Coccyx Epidural anesthesia Lumbar puncture Pia mater Skin Lamina Fascia Epidural space Ligamentum flavum Conus medullaris End of dural sac Subarachnoid space containing CSF Dura mater Epidural space B L1 L2 L3 L4 L5 S1 Filum terminale (Pia mater) S4 S5 S2 S3 Sacrum Arachnoid Coccyx Figure II-1-6. Important Vertebral Levels Figure II-1-6. Important Vertebral Levels SPINAL NERVES There are 31 pairs of spinal nerves attached to each segment of the spinal cord: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal. The spinal nerves with the cranial nerves form part of the peripheral nervous system. 33 USMLE Step 1 Anatomy.indb 33 9/15/17 10:51 AM Part II l Gross Anatomy Anatomy Pharmacology Immunology Dorsal ramus (mixed) Arachnoid White matter Supplies: • Skin of back and dorsal neck • Deep intrinsic back muscles (Erector spinae) Biochemistry Dura mater Gray matter Pia mater Dorsal root (sensory) Physiology Medical Genetics Pathology Behavioral Science/Social Sciences Dorsal root ganglion Ventral root (motor) Microbiology Spinal nerve (mixed) Ventral ramus (mixed) Sympathetic ganglion Supplies: • Skin of anterolateral trunk and limbs • Skeletal muscles of anterolateral trunk and limbs Figure II-1-7.ofCross Section Spinal Cord and Nerve Figure II-1-7. Cross Section Spinal Cord of and Parts of Spinal Parts of Spinal Nerve Each spinal nerve is formed by the following components: • Dorsal root carries sensory fibers from the periphery into the dorsal aspect of the spinal cord; on each dorsal root there is a dorsal root ganglion (sensory) containing the pseudounipolar cell bodies of the nerve fibers that are found in the dorsal root • Ventral root arises from the ventral aspect of the spinal cord and car- ries axons of motor neurons from the spinal cord to the periphery; the cell bodies of the axons in the ventral root are located in the ventral or lateral horns of the spinal cord gray matter • Spinal nerve is formed by the union of the ventral and dorsal roots; it exits the vertebral column by passing through the intervertebral foramen • Dorsal rami innervate the skin of the dorsal surface of the back, neck, zygapophyseal joints, and intrinsic skeletal muscles of the deep back • Ventral rami innervate the skin of the anterolateral trunk and limbs, and the skeletal muscles of the anterolateral trunk and limbs (ventral rami form the brachial and lumbosacral plexuses) 34 USMLE Step 1 Anatomy.indb 34 9/15/17 10:51 AM Chapter 1 l Back and Autonomic Nervous System The spinal nerves exit the vertebral column by a specific relationship to the vertebrae. The cervical nerves C1–C7 exit the intervertebral foramina superior to the pedicles of the same-numbered vertebrae. The C8 nerve exits the intervertebral foramen inferior to the C7 pedicle. This is the transition point. All nerves beginning with T1 and below will exit the intervertebral foramina inferior to the pedicle of the same-numbered vertebrae. Lumbar Puncture A lumbar puncture is used to inject anesthetic material in the epidural space or to withdraw CSF from the subarachnoid space. • A spinal tap is typically performed at the L4-L5 interspace. • A horizontal line drawn at the top of the iliac crest marks the level of the L4 vertebra. • When a lumbar puncture is performed in the midline, the needle passes through the interlaminar space of the vertebral column found between the laminae of the lumbar vertebrae. • The interlaminar spaces are covered by the highly elastic ligamenta flava. Clinical Correlate Lumbar vertebrae Interlaminar spaces (covered by ligamentum flavum) During a lumbar puncture, a needle is passed through the interlaminar space while the vertebral column is flexed. The needle passes through the following layers: • Skin • Superficial fascia • Deep fascia • Supraspinous ligament Sacrum • Interspinous ligament • Interlaminar space Coccyx FigureII-1-8. II-1-8. Interlaminar Spaces Figure Interlaminar Spaces • Epidural space • Dura • Arachnoid • Subarachnoid space 35 USMLE Step 1 Anatomy.indb 35 9/15/17 10:51 AM Part II Anatomy Pharmacology l Gross Anatomy Immunology Biochemistry AUTONOMIC NERVOUS SYSTEM The autonomic nervous system (ANS) is concerned with the motor innervation of smooth muscle, cardiac muscle, and glands of the body. Anatomically and functionally, it is composed of 2 motor divisions: sympathetic and parasympathetic. In both divisions, 2 neurons form an autonomic pathway. • Preganglionic neurons have their neuronal cell bodies in the CNS Physiology (formed by neuroectoderm); their axons exit in cranial and spinal nerves. Medical Genetics • Postganglionic neurons have cell bodies in autonomic ganglia in the peripheral nervous system (PNS) (formed by neural crest cells) Pathology Behavioral Science/Social Sciences Central nervous system (CNS) Motor ganglion Preganglionic nerve fiber Microbiology Postganglionic nerve fiber Target Figure FigureII-1-9. II-1-9.Autonomic AutonomicNervous Nervous System System Sympathetic Nervous System The preganglionic cell bodies of the sympathetic nervous system are found in the lateral horn gray matter of spinal cord segments T1–L2 (14 segments). The postganglionic cell bodies of the sympathetic system are found in one of 2 types of motor ganglia in the PNS: • Chain or paravertebral • Collateral or prevertebral (found only in abdomen or pelvis) Table II-1-1. Sympathetic = Thoracolumbar Outflow Origin (Preganglionic) Site of Synapse (Postganglionic) Innervation (Target) Spinal cord levels T1–L2 Sympathetic chain ganglia (paravertebral ganglia) Smooth muscle, cardiac muscle and glands of body wall and limbs (T1–L2), head (T1–2) and thoracic viscera (T1–5). Thoracic splanchnic nerves T5–T12 Prevertebral ganglia (collateral) (e.g., celiac, aorticorenal, superior mesenteric ganglia) Smooth muscle and glands of the foregut and midgut Lumbar splanchnic nerves L1–L2 Prevertebral ganglia (collateral) (e.g., inferior mesenteric and pelvic ganglia) Smooth muscle and glands of the pelvic viscera and hindgut 36 USMLE Step 1 Anatomy.indb 36 9/15/17 10:51 AM Chapter 1 Hypothalamus Back and Autonomic Nervous System Head (sweat glands, dilator pupillae m., superior tarsal m.) III IV V VI VII VIII l Internal carotid a. External carotid a. IX X XI X C1 Descending hypothalamic fibers (drive all preganglionic T1 sympathetic neurons) m: muscle a: artery (Periarterial carotid nerve plexus) Superior cervical ganglion Middle cervical ganglion Lesions at arrows result in ipsilateral Horner syndrome (ptosis, miosis, and anhydrosis). Cervicothoracic ganglion Heart, trachea, bronchi, lungs (thorax) * Thoracic *Splanchnic * nerves (T5–T12) L1 L2 Prevertebral ganglia Sympathetic chain Smooth muscle and glands of the foregut and midgut Prevertebral ganglia *Gray rami carry postganglionic sympathetic axons from the sympathetic ganglion to the spinal nerve. Lumbar splanchnic nerves (L1-L2) Smooth muscle and glands of the hindgut and pelvic viscera Preganglionic Postganglionic Figure II-1-10. Overview of Sympathetic Outflow Figure II-1-10. Overview of Sympathetic Outflow 37 USMLE Step 1 Anatomy.indb 37 9/15/17 10:51 AM Part II Anatomy l Gross Anatomy Immunology Preganglionic Postganglionic Pharmacology Biochemistry Physiology Medical Genetics Lateral horn (T1–L2) Dorsal ramus Pathology Ventral ramus Behavioral Science/Social Sciences Spinal nerve Gray ramus communicans– postganglionics (31) (to body wall) Microbiology White ramus communicans– preganglionics (14) To smooth muscles and glands of body wall and limbs Sympathetic chain ganglion Figure II-1-11. Cross Section of Section Spinal Cord Showing Sympathetic OutflowOutflow Figure II-1-11. Cross of Spinal Cord Showing Sympathetic Note Parasympathetic Nervous System White rami are preganglionic sympathetics that all enter the sympathetic trunk of ganglia. They may synapse with ganglion at point of entry or go up or down and synapse above or below point of entry. If a white ramus does not synapse, it passes through ganglion and becomes a root of a thoracic or lumbar splanchnic nerve. The preganglionic cell bodies of the parasympathetic nervous system are found in the CNS in one of 2 places: • Gray matter of brain stem associated with cranial nerves III, VII, IX, and X, or • Spinal cord gray in sacral segments S2 3, and 4 (pelvic splanchnics) The postganglionic cell bodies of the parasympathetic nervous system are found in terminal ganglia in the PNS that are usually located near the organ innervated or in the wall of the organ. Table II-1-2. Parasympathetic = Craniosacral Outflow Origin (Preganglionic) Site of Synapse (Postganglionic) Innervation (Target) Cranial nerves III, VII, IX 4 cranial ganglia Glands and smooth muscle of the head Cranial nerve X Terminal ganglia (in or near the walls of viscera) Viscera of the neck, thorax, foregut, and midgut Pelvic splanchnic nerves S 2, 3, 4 Terminal ganglia (in or near the walls of viscera) Hindgut and pelvic viscera (including the bladder, rectum, and erectile tissue) 38 USMLE Step 1 Anatomy.indb 38 9/15/17 10:51 AM Chapter 1 l Back and Autonomic Nervous System Parasympathetic Nervous System Ciliary Pupillary sphincter Ciliary m. ganglion Submandibular III ganglion Submandibular gland V Pterygopalatine Sublingual gland Head ganglion VII Lacrimal gland Nasal and oral IX mucosal glands X Otic Parotid gland ganglion Viscera of the Terminal thorax and abdomen ganglia (foregut and midgut) Midbrain Pons Medulla C1 T1 Preganglionic Postganglionic L1 Hindgut and pelvic viscera (including the bladder, erectile tissue, and rectum) Terminal ganglia Pelvic splanchnics S2 S3 S4 Figure II-1-12. Outflow Figure II-1-12. Overview OverviewofofParasympathetic Parasympathetic Outflow 39 USMLE Step 1 Anatomy.indb 39 9/15/17 10:51 AM USMLE Step 1 Anatomy.indb 40 9/15/17 10:51 AM N II Thorax 2 Learning Objectives ❏❏ Solve problems concerning the chest wall ❏❏ Use knowledge of embryology of lower respiratory system ❏❏ Use knowledge of pleura and pleural cavity ❏❏ Interpret scenarios on respiratory histology ❏❏ Use knowledge of alveolar ducts, alveolar sacs, and the alveoli ❏❏ Answer questions about embryology of the heart ❏❏ Solve problems concerning the mediastinum ❏❏ Interpret scenarios on heart histology ❏❏ Solve problems concerning the diaphragm CHEST WALL Breast The breast (mammary gland) is a subcutaneous glandular organ of the superficial pectoral region. It is a modified sweat gland, specialized in women for the production and secretion of milk. A variable amount of fat surrounds the glandular tissue and duct system and is responsible for the shape and size of the female breast. • Cooper ligaments are suspensory ligaments that attach the mammary gland to the skin and run from the skin to the deep fascia. • There is an extensive blood supply to the mammary tissues. The 2 prominent blood supplies are: –– Internal thoracic artery (internal mammary), a branch of the subclavian artery which supplies medial aspect of the gland –– Lateral thoracic artery, a branch of the axillary artery which contributes to the blood supply to lateral part of the gland; lateral aspect of the chest wall, the lateral thoracic artery courses with the long thoracic nerve, superficial to serratus anterior muscle Clinical Correlate The presence of a tumor within the breast can distort Cooper ligaments, which results in dimpling of the skin (orange-peel appearance). Clinical Correlate During a radical mastectomy, the long thoracic nerve (serratus anterior muscle) may be lesioned during ligation of the lateral thoracic artery. A few weeks after surgery, the patient may present with a winged scapula and weakness in abduction of the arm above 90°. The thoracodorsal nerve supplying the latissimus dorsi muscle may also be damaged during mastectomy, resulting in weakness in extension and medial rotation of the arm. 41 USMLE Step 1 Anatomy.indb 41 9/15/17 10:51 AM Part II l Anatomy Gross Anatomy Immunology • The lymphatic drainage of the breast is critical due to its important role in metastasis of breast cancer. The lymphatic drainage of the breast follows 2 primary routes: Pharmacology Biochemistry Physiology Medical Genetics Pathology Behavioral Science/Social Sciences (Parasternal) internal thoracic nodes Microbiology –– Laterally, most of the lymphatic flow (75%) drains from the nipple and the superior, lateral, and inferior quadrants of the breast to the axillary nodes, initially to the pectoral group. –– From the medial quadrant, most lymph drains to the parasternal nodes, which accompany the internal thoracic vessels. It is also through this medial route that cancer can spread to the opposite breast. Subclavian nodes Interpectoral nodes Sagittal View of Breast Axillary nodes Subcutaneous fat Brachial nodes Subscapular nodes Pectoral nodes Suspensory ligaments (Cooper) Gland lobules Lactiferous duct Lactiferous sinus Figure II-2-1. Breast Figure II-2-1. Breast EMBRYOLOGY OF LOWER RESPIRATORY SYSTEM During week 4 of development, the lower respiratory system (trachea, bronchi, and lungs) begins to develop as a single respiratory (laryngotracheal) diverticulum of endoderm from the ventral wall of the foregut. The respiratory epithelium develops from endoderm while the muscles, connective tissues, and cartilages develop from mesoderm. • The respiratory diverticulum enlarges distally to form the lung bud. • The diverticulum and lung bud then bifurcate into the 2 bronchial buds, which then undergo a series of divisions to form the major part of the bronchial tree (main, secondary, and tertiary bronchi) by month 6. • The tertiary segmental bronchi are related to the bronchopulmonary segments of the lungs. 42 USMLE Step 1 Anatomy.indb 42 9/15/17 10:51 AM Chapter 2 l Thorax • To separate the initial communication with foregut, the tracheoesophageal septum forms to separate the esophagus from the trachea. • A critical time in lung development is the 25–28th weeks. By this time, the Type I and II pneumocytes are present and gas exchange and surfactant production are possible. Premature fetuses born during this time can survive with intensive care. The amount of surfactant production is critical. Tracheoesophageal septum Foregut Esophagus Respiratory diverticulum Lung bud Trachea Esophagus Bronchial buds Figure II-2-2. Development the Lower Respiratory Figure II-2-2. Development of theofLower Respiratory System System A tracheoesophageal fistula is an abnormal communication between the trachea and esophagus caused by a malformation of the tracheoesophageal septum. It is generally associated with the following: • Esophageal atresia and polyhydramnios (increased volume of amni- otic fluid) • Regurgitation of milk • Gagging and cyanosis after feeding • Abdominal distention after crying • Reflux of gastric contents into lungs causing pneumonitis The fistula is most commonly (90% of cases) located between the esophagus and distal third of the trachea. 43 USMLE Step 1 Anatomy.indb 43 9/15/17 10:51 AM Part II l Gross Anatomy Anatomy Immunology Clinical Correlate Pulmonary hypoplasia occurs when lung development is stunted. This Pharmacology condition has 2 congenitalBiochemistry causes: (1) congenital diaphragmatic hernia (a herniation of abdominal contents into the thorax, which affects the or (2) Physiologydevelopment of the left lung), Medical Genetics bilateral renal agenesis (this causes oligohydramnios, which increases the pressure on the fetal thorax and Potter’s sequence). One of the features Pathology Behavioral Science/Social Sciences of Potter’s sequence is bilateral pulmonary hypoplasia. Microbiology Trachea Tracheoesophageal fistula Esophagus Bronchi Gastric acids Figure Fistula(Most (MostCommon Common Type) FigureII-2-3. II-2-3.Tracheoesophageal Tracheoesophageal Fistula Type) ADULT THORACIC CAVITY The thoracic cavity is kidney-shaped on cross section and is bounded anterolaterally by the bony thorax (sternum, ribs, and intercostal spaces) and posteriorly by the thoracic vertebrae. Superiorly, the thoracic cavity communicates through the thoracic inlet with the base of the neck. (Note, however, that clinically this region is usually called the thoracic outlet.) Inferiorly, the thoracic outlet is closed by the diaphragm which separates the thoracic from the abdominal cavity. The thoracic cavity is divided into 2 lateral compartments: the lungs and their covering of serous membranes, and a central compartment called the mediastinum which contains most of the viscera of the thorax. Clinical Correlate Passage of instruments through the intercostal space is done in the lower part of the space to avoid the intercostal neurovascular structures (as during a thoracentesis). An intercostal nerve block is done in the upper portion of the intercostal space. Intercostal Spaces • There are 11 intercostal spaces within the thoracic wall (Figure II- 2-4A). The spaces are filled in by 3 layers of intercostal muscles and their related fasciae and are bounded superiorly and inferiorly by the adjacent ribs. • The costal groove is located along the inferior border of each rib (upper aspect of the intercostal space) and provides protection for the intercostal nerve, artery, and vein which are located in the groove. The vein is most superior and the nerve is inferior in the groove (VAN). • The intercostal arteries are contributed to anteriorly from branches of the internal thoracic artery (branch of the subclavian artery) and posteriorly from branches of the thoracic aorta. Thus, the intercostal arteries can provide a potential collateral circulation between the subclavian artery and the thoracic aorta. 44 USMLE Step 1 Anatomy.indb 44 9/15/17 10:51 AM Chapter 2 First rib Clavicle Sternum Second rib Scapula Rib 2 Rib 6 Rib 8 Posterior mediastinum T12 Body of sternum Anterior mediastinum Esophagus Left lung Right lung Thoracic vertebra Costochondral junction A. Thoracic Wall Thorax Middle mediastinum Manubrium of sternum Sternal angle (of Louis) l Descending aorta B. (Transverse section) thoracic cavity Figure II-2-4. Thoracic Cavity Figure II-2-4. Thoracic Cavity PLEURA AND PLEURAL CAVITY Clinical Correlate Within the thoracic and abdominal cavities there are 3 serous mesodermalderived membranes which form a covering for the lungs (pleura), heart (pericardium), and abdominal viscera (peritoneum). Respiratory distress syndrome is caused by a deficiency of surfactant (type II pneumocytes). This condition is associated with premature infants, infants of diabetic mothers, and prolonged intrauterine asphyxia. Thyroxine and cortisol treatment increase the production of surfactant. Each of these double-layered membranes permits friction-reducing movements of the viscera against adjacent structures. The outer layer of the serous membranes is referred to as the parietal layer; and the inner layer which is applied directly to the surface of the organ is called the visceral layer. The 2 layers are continuous and there is a potential space (pleural cavity) between the parietal and visceral layers containing a thin layer of serous fluid. Pleura The pleura is the serous membrane that invests the lungs in the lateral compartments of the thoracic cavity (Figure II-2-5). The external parietal pleura lines and attaches to the inner surfaces of the chest wall, diaphragm, and mediastinum. The innermost visceral layer reflects from the parietal layer at the hilum of the lungs and is firmly attached to and follows the contours of the lung. Visceral and parietal pleura are continuous at the root of the lung. Surfactant deficiency may lead to hyaline membrane disease, whereby repeated gasping inhalations damage the alveolar lining. Hyaline membrane disease is characterized histologically by collapsed alveoli (atelectasis) and eosinophilic (pink) fluid covering the alveoli. The parietal pleura is regionally named by its relationship to the thoracic wall and mediastinum (Figure II-2-5): • Costal parietal pleura is lateral and lines the inner surfaces of the ribs and intercostal spaces • Diaphragmatic parietal pleura lines the thoracic surface of the dia- phragm 45 USMLE Step 1 Anatomy.indb 45 9/15/17 10:51 AM Part II l Gross Anatomy Anatomy Immunology • Mediastinal parietal pleura is medial and lines the mediastinum. The mediastinal pleura reflects and becomes continuous with the visceral pleura at the hilum. Pharmacology Biochemistry • Cervical parietal pleura extends into the neck above the first rib where it covers the apex of the lung. Physiology Medical Genetics Clinical Correlate Inflammation of the parietal pleural layers (pleurisy) produces sharp pain Pathology Behavioral Science/Social Sciences upon respiration. Costal inflammation produces local dermatome pain of the chest wall via the intercostal nerves; whereby mediastinal irritation produces referred pain via the phrenic Microbiology nerve to the shoulder dermatomes of C3–5. The visceral pleura tightly invests the surface of the lungs, following all of the fissures and lobes of the lung. Innervation of Pleura The parietal pleura has extensive somatic sensory innervation provided by nerves closely related to different aspects of the pleura. • The intercostal nerves supply the costal and peripheral portions of the diaphragmatic pleura. • The phrenic nerve supplies the central portion of the diaphragmatic pleura and the mediastinal pleura. The visceral pleura is supplied by visceral sensory nerves that course with the autonomic nerves. Clinical Correlate Open pneumothorax occurs when air enters the pleural cavity following a penetrating wound of the chest cavity. Air moves freely through the wound during inspiration and expiration. During inspiration, air enters the chest wall and the mediastinum will shift toward other side and compress the opposite lung. During expiration, air exits the wound and the mediastinum moves back toward the affected side. Tension pneumothorax occurs when a piece of tissue covers and forms a flap over the wound. During inspiration, air enters the chest cavity, which results in a shift of the mediastinum toward the other side, compressing the opposite lung. During expiration, the piece of tissue prevents the air from escaping the wound, which increases the pressure and the shift toward the opposite side is enhanced. This severely reduces the opposite lung function and venous return to the heart and can be life-threatening. Cervical pleura Hilum Mediastinal pleura Lung Costal pleura Parietal pleura Visceral pleura Pleural cavity Diaphragm Costodiaphragmatic recess 8th rib Diaphragmatic pleura 10th rib Figure II-2-5. Layers of the Pleura Figure II-2-5. Layers of the Pleura The pleural cavity is the potential space between the parietal and visceral layers of the pleura. It is a closed space which contains a small amount of serous fluid that lubricates the opposing parietal and visceral layers. The introduction of air into the pleural cavity may cause the lung to collapse, resulting in a pneumothorax which causes shortness of breath and painful respiration. The lung collapses due to the loss of the negative pressure of the pleural cavity during a pneumothorax. 46 USMLE Step 1 Anatomy.indb 46 9/15/17 10:51 AM Chapter 2 l Thorax Pleural Reflections Pleural reflections are the areas where the parietal pleura abruptly changes direction from one wall to the other, outlining the extent of the pleural cavities. • The sternal line of reflection is where the costal pleura is continuous with the mediastinal pleura posterior to the sternum (from costal cartilages 2–4). The pleural margin then passes inferiorly to the level of the sixth costal cartilage. • Around the chest wall, there are 2 rib interspaces separating the inferior limit of parietal pleural reflections from the inferior border of the lungs and visceral pleura: between ribs 6–8 in the midclavicular line, ribs 8–10 in the midaxillary line, and ribs 10–12 at the vertebral column (paravertebral line), respectively. Midclavicular line Costomediastinal recesses Midaxillary line Paravertebral line Rib 8 Rib 8 Rib 10 Rib 10 Costodiaphragmatic recesses Costodiaphragmatic recesses Anterior View Posterior View Costodiaphragmatic recesses Lateral View Figure II-2-6. Pleural Reflections and Recesses Figure II-2-6. Pleural Reflections and Recesses Pleural Recesses Note Pleural recesses are potential spaces not occupied by lung tissue except during deep inspiration. Visceral Pleura Parietal Pleura Midclavicular line 6th rib 8th rib Midaxillary line 8th rib 10th rib Paravertebral line 10th rib 12th rib • Costodiaphragmatic recesses are spaces below the inferior borders of the lungs where costal and diaphragmatic pleura are in contact. • The costomediastinal recess is a space where the left costal and mediastinal parietal pleura meet, leaving a space caused by the cardiac notch of the left lung. This space is occupied by the lingula of the left lung during inspiration. 47 USMLE Step 1 Anatomy.indb 47 9/15/17 10:51 AM Part II l Gross Anatomy Anatomy Immunology Pharmacology Biochemistry Physiology Medical Genetics LUNGS The lungs and the pleural membranes are located in the lateral compartment of the thoracic cavity. The lungs are separated from each other in the midline by the mediastinum. The hilum of the lung is on the medial surface and serves for passage of structures in the root of the lung: the pulmonary vessels, primary bronchi, nerves, and lymphatics. Surfaces and Regions Each lung has 3 surfaces: • The costal surface is smooth and convex and is related laterally to the Pathology Behavioral Science/Social Sciences ribs and tissues of the chest wall. • The mediastinal surface is concave and is related medially to the Microbiology middle mediastinum and the heart. The mediastinal surfaces contain the root of the lung and a deep cardiac impression, more pronounced on the left lung. • The diaphragmatic surface (base) is concave and rests on the superior surface of the diaphragm. It is more superior on the right owing to the presence of the liver. Clinical Correlate A tumor at the apex of the lung (Pancoast tumor) may result in thoracic outlet syndrome. Apex Hilum Lung Costal surface Mediastinal surface Diaphragm 8th rib Costodiaphragmatic recess 10th rib Diaphragmatic surface Figure II-2-7. Surfaces of the Lung Figure II-2-7. Surfaces of the Lung The apex (cupola) of the lung projects superiorly into the root of the neck above the level of the first rib and is crossed anteriorly by the subclavian artery and vein. Lobes and Fissures The right lung is divided into 3 lobes (superior, middle, inferior) separated by 2 fissures, the horizontal and oblique fissures. The horizontal fissure separates the superior from the middle lobe and the oblique fissure separates the middle from the inferior lobe. 48 USMLE Step 1 Anatomy.indb 48 9/15/17 10:51 AM Chapter 2 The left lung is divided into 2 lobes (superior, inferior) separated by an oblique fissure. The lingula of the upper lobe of the left lung corresponds to the middle lobe of the right lung. • The oblique fissure of both lungs projects anteriorly at approximately the 5th intercostal space in the midclavicular line, ending medially deep to the 6th costal cartilage. • The horizontal fissure runs horizontally from the oblique fissure in the right 5th intercostal space to the right 4th costal cartilage. l Thorax Clinical Correlate The superior lobe of the right lung projects anteriorly on the chest wall above the 4th rib and the middle lobe projects anteriorly below the 4th rib. A small portion of the inferior lobe of both lungs projects below the 6th rib anteriorly but primarily projects to the posterior chest wall. Clinical Correlate • T o listen to breath sounds of the superior lobes of the right and left lungs, the stethoscope is placed on the superior area of the anterior chest wall (above the 4th rib for the right lung). Horizontal fissure Trachea Right lung Left lung Superior lobe Superior lobe Middle lobe Oblique fissure Inferior lobe Oblique fissure Inferior lobe Diaphragm Mediastinum FigureII-2-8. II-2-8.Lobes Lobes and and Fissures Fissures ofofLungs Figure Lungs Lymphatic System • F or breath sounds from the middle lobe of the right lung, the stethoscope is placed on the anterior chest wall inferior to the 4th rib and medially toward the sternum. • F or the inferior lobes of both lungs, breath sounds are primarily heard on the posterior chest wall. Clinical Correlate Aspiration of a foreign body will more often enter the right primary bronchus, which is shorter, wider, and more vertical than the left primary bronchus. When the individual is vertical, the foreign body usually falls into the posterior basal segment of the right inferior lobe. The lymphatic system consists of an extensive network of lymph capillaries, vessels, and nodes that drain extracellular fluid from most of the body tissues and organs. The lymph flow will return to the blood venous system by 2 major lymphatic vessels, the right lymphatic duct and the thoracic duct on the left (Figure II-2-10A). These 2 vessels drain into the junction of the internal jugular and the subclavian veins on their respective sides. 49 USMLE Step 1 Anatomy.indb 49 9/15/17 10:51 AM Part II l Gross Anatomy Anatomy Immunology • The thoracic duct carries all lymphatic drainage from the body below the diaphragm and on the left side of the trunk and head above the diaphragm (Figure II-2-10B). Pharmacology Biochemistry • The right lymphatic duct drains lymph flow from the right head and neck and the right side of the trunk above the diaphragm (Figure II2-10B). Physiology Pathology Medical Genetics Behavioral Science/Social Sciences Lymphatic Drainage The lymphatic drainage of the lungs is extensive and drains by way of superficial and deep lymphatic plexuses. The superficial plexus is immediately deep to the visceral pleura. The deep plexus begins deeply in the lungs and drains through pulmonary nodes which follow the bronchial tree toward the hilum. The major nodes involved in the lymphatic drainage of these 2 plexuses are: Microbiology • Bronchopulmonary (hilar) nodes are located at the hilum of the lungs. They receive lymph drainage from both superficial and deep lymphatic plexuses, and they drain into the tracheobronchial nodes. • Tracheobronchial nodes are located at the bifurcation of the trachea, and they drain into the right and left bronchomediastinal nodes and trunk. • Bronchomediastinal nodes and trunk are located on the right and left sides of the trachea, and they drain superiorly into either the right lymphatic duct or the thoracic duct on the left. Right Lung Clinical Correlate The lymphatic drainage from the lower lobe of the left lung also drains across the midline into the right bronchomediastinal lymphatic trunk and nodes, then continues along the right pathway to the right lymphatic duct. This is important to consider with metastasis of lung cancer. To right lymphatic duct Trachea Bronchomediastinal nodes Left Lung To thoracic duct Tracheobronchial nodes Tracheobronchial nodes Bronchopulmonary nodes Bronchopulmonary nodes Diaphragm Figure II-2-9. Lungs Figure II-2-9.Lymphatics Lymphaticsofofthe the Lungs 50 USMLE Step 1 Anatomy.indb 50 9/15/17 10:51 AM Chapter 2 From head and neck Right lymphatic duct Thoracic duct From upper limb & neck Right bronchomediastinal trunk Left internal jugular vein Area draining to right lymphatic duct l Thorax Area draining to thoracic duct From upper limb and neck Left subclavian vein Left bronchomediastinal trunk A. Right lymphatic and thoracic ducts B. General lymphatic drainage Figure II-2-10. Drainage Figure II-2-10. Lymphatic RESPIRATORY HISTOLOGY The lung is an organ that functions in the intake of oxygen and exhaling of CO2. Approximately 14 times each minute, we take in about 500 mL of air per breath. Inspired air will be spread over 120 square meters of the surface area of the lungs. The air–blood barrier has to be thin enough for air to pass across but tough enough to keep the blood cells inside their capillaries. Because lungs are opened to the outside world, they are susceptible to environmental insults in the form of pollution and infectious bacteria. The lungs receive the entire cardiac output and are positioned to modify various blood components. The pulmonary endothelium plays an active role in the metabolic transformation of lipoproteins and prostaglandins. The enzyme that converts angiotensin I to angiotensin II is produced by the lung endothelial cells. Clinical Correlate Any disease that affects capillaries also affects the extensive capillary bed of the lungs. Bacteria which colonize the lungs may damage the barriers between the alveoli and the capillaries, gaining access to the bloodstream (a common complication of bacterial pneumonia). • W ith allergies, smooth-muscle constriction reduces the diameter of air tubes and results in reduced air intake. • L ung cancers commonly develop from bronchi (smoking, asbestos, and excessive radiation are the main causes). esothelioma is a malignant • M tumor of the pleura (causative agent: asbestos dust). 51 USMLE Step 1 Anatomy.indb 51 9/15/17 10:51 AM Part II l Gross Anatomy Anatomy Immunology Paranasal sinuses Pharmacology Biochemistry Frontal sinus Physiology Medical Genetics Olfactory area Pathology Sphenoid sinus Pharyngeal tonsil Behavioral Science/Social Sciences Nasal conchae Nasopharynx Microbiology Oropharynx Larynx Laryngopharynx Trachea Figure II-2-11.Respiratory RespiratoryPathways Pathways Figure II-2-11. Table II-2-1. Histologic Features of Trachea, Bronchi, and Bronchioles Trachea Bronchi Bronchioles Epithelia Pseudostratified ciliated columnar (PCC) cells, goblet cells PCC to simple columnar cells Ciliated, some goblet cells, Clara cells in terminal bronchioles Cartilage 16–20 C-shaped cartilaginous rings Irregular plates None Glands Seromucous glands Fewer seromucous glands None Smooth muscle Between open ends of C-shaped cartilage Prominent Highest proportion of smooth muscle in the bronchial tree Elastic fibers Present Abundant Abundant 52 USMLE Step 1 Anatomy.indb 52 9/15/17 10:51 AM Chapter 2 l Thorax TRACHEA The trachea is a hollow tube, about 10 cm in length (and about 2 cm in diameter), extending from the larynx to its bifurcation at the carina to form a primary bronchus for each lung. The most striking structures of the trachea are the C-shaped hyaline cartilage rings. In the human there are 16–20 of them distributed along the length of the trachea. The rings overlap in the anterior part of the trachea. The free posterior ends of the C-shaped cartilages are interconnected by smooth-muscle cells. Copyright McGraw-Hill Used permission. Copyright McGraw-HillCompanies. Companies. Usedwith with permission. Figure II-2-12. Trachea with a hyaline cartilage ring (arrow) Figure II-2-12. Trachea with a hyaline cartilage ring (arrow) and and pseudostratified columnar epithelium pseudostratified columnar epithelium The trachea is composed of concentric rings of mucosa, submucosa, an incomplete muscularis, and an complete adventitia. • The mucosa has 3 components: a pseudostratified epithelium, an underlying vascularized loose connective tissue (lamina propria) that contains immune cells, and a thin layer of smooth-muscle cells (muscularis mucosa). • The submucosa is a vascular service area containing large blood ves- sels. Collagen fibers, lymphatic vessels and nerves are also present in this layer. • The outside covering of the trachea, the adventitia, is composed of several layers of loose connective tissue. The epithelial lining of the trachea and bronchi is pseudostratified columnar in which all cells lie on the same basal membrane but only some reach the luminal surface. The only other place in the body with this epithelium is the male reproductive tract. 53 USMLE Step 1 Anatomy.indb 53 9/15/17 10:51 AM Part II l Gross Anatomy Anatomy Immunology Clinical Correlate If mucosal clearance is ineffective, or the mechanism overwhelmed, Pharmacology Biochemistryor infection (pathogenic bacteria) pneumoconiosis (dust-related disease) may follow. In cystic fibrosis, the secreted mucous Medical Genetics is thick or viscous and the cilia have a difficult time moving it toward the pharynx. Patients with this disease have frequent infections of the Pathologyrespiratory system. Behavioral Science/Social Sciences Physiology Microbiology Copyright McGraw-Hill Companies. Used with permission. Copyright McGraw-Hill Companies. Used with permission. Figure II-2-13. Pseudostratified columnar epithelium with goblet Figure II-2-13. Pseudostratified Columnar Epithelium with Goblet Cells cells (arrowhead) surrounded by ciliated cells (arrow) (arrowhead) Surrounded by Ciliated Cells (arrow) Clinical Correlate Patients lacking dynein have immotile cilia or Kartagener syndrome. With immotile cilia, patients are subject to many respiratory problems because their cilia cannot move this mucous layer with its trapped bacteria. Males also possess immotile sperm. Tracheal Epithelial Cell Types Columnar cells extend from the basal membrane to the luminal surface. These cells contain 200–300 apical cilia per cell that are intermingled with microvilli. The cilia are motile and beat to help move the secreted mucous layer over the lining of the trachea and out of the respiratory system. Goblet cells secrete a polysaccharide mucous material into the lumen of trachea. Mucous production is supplemented by secretions of the submucosal mixed glands. The mucous layer of the respiratory system traps particulate substances (dust, bacteria, and viruses) and absorbs noxious water-soluble gases such as ozone and sulfur dioxide. The mucous sticky layer is moved by the beating cilia toward the pharynx where it is swallowed. This movement is known as the mucociliary escalator system. Most material (dust and bacteria) is trapped in the mucous layer, and is removed and digested. Pulmonary neuroendocrine (PNE) cells are comparable to the endocrine cells in the gut. These epithelial neuroendocrine cells have been given various names: • APUD cells (Amino-Precursor-Uptake-Decarboxylase), DNES cells (Diffuse Neuro Endocrine System) and K (Kulchitsky) cells. These cells occur in clusters and are often located at airway branch points. • Brush cells may represent goblet cells that have secreted their products or intermediate stages in the formation of goblet or the tall ciliated cells. They have short microvilli on their apical surfaces. Some of these cells have synapses with intraepithelial nerves, suggesting that these cells may be sensory receptors. 54 USMLE Step 1 Anatomy.indb 54 9/15/17 10:51 AM Chapter 2 Basal cells are stem cells for the ciliated and goblet cells. The stem cells lie on the basal membrane but do not extend to the lumen of the trachea. These cells, along with the epithelial neuroendocrine cells, are responsible for the pseudostratified appearance of the trachea. BRONCHI The bronchial tree forms a branching airway from the trachea to the bronchioles. When the primary bronchi enter the lung, they give rise to 5 secondary or lobar bronchi—3 for the right lung and 2 for the left. The 5 lobes are further subdivided into 10 tertiary or segmental bronchi in each lung, which form bronchopulmonary segments. l Thorax Clinical Correlate The columnar and goblet cells are sensitive to irritation. The ciliated cells become taller, and there is an increase in the number of goblet cells and submucosal glands. Intensive irritation from smoking leads to a squamous metaplasia where the ciliated epithelium becomes a squamous epithelium. This process is reversible. Clinical Correlate Bronchial metastatic tumors arise from Kulchitsky cells. Copyright McGraw-Hill McGraw-Hill Companies. permission. Copyright Companies.Used Usedwith with permission. Figure II-2-14. Bronchus with a plate of cartilage (arrow) Figure II-2-14. Bronchus with a Plate of Cartilage (arrow) The epithelial lining of the bronchi is also pseudostratified. It consists of ciliated columnar cells, basal cells, mucous cells, brush cells and neuroendocrine (APUD, DNES, or K) cells. There are also seromucous glands in the submucosa that empty onto the epithelial surface via ducts. The walls of bronchi contain irregular plates of cartilage and circular smooth-muscle fascicles bound together by elastic fibers. The number of goblet cells and submucosa glands decreases from the trachea to the small bronchi. BRONCHIOLES The wall of a bronchiole does not contain cartilage or glands. The smooth-muscle fascicles are bound together by elastic fibers. The epithelium is still ciliated, but is a simple cuboidal or columnar epithelium rather than pseudostratified. The epithelial lining of the airway is composed of ciliated cells (goblet and basal cells are absent in the terminal bronchioles) and an additional type called the Clara cell. Clinical Correlate Cystic fibrosis can result in abnormally thick mucous, in part due to defective chloride transport by Clara cells. 55 USMLE Step 1 Anatomy.indb 55 9/15/17 10:51 AM Part II l Gross Anatomy Anatomy Immunology Pharmacology Biochemistry Physiology Medical Genetics Clara cells (also called bronchiolar secretory cells) are nonciliated and secrete a serous solution similar to surfactant. They aid in the detoxification of airborne toxins, and serve as a stem cell for the ciliated cells and for themselves. The number of Clara cells increases in response to increased levels of pollutants like cigarette smoke. Clara cells are most abundant in the terminal bronchioles, where they make up about 80% of the epithelial cell lining; they are also involved with chloride ion transport into the lumens of the terminal bronchioles. Clinical Correlate Chronic obstructive pulmonary disease Behavioral Science/Social Sciences (COPD) affects the bronchioles and includes emphysema and asthma. Pathology Microbiology • Emphysema is caused by a loss of elastic fibers and results in chronic airflow obstruction. • Asthma is a chronic process characterized by a reversible narrowing of airways. • Asthma is reversible; emphysema is not. Copyright McGraw-Hill Used with permission. Copyright McGraw-HillCompanies. Companies. Used with permission. Figure II-2-15. Terminal bronchiole lumen (asterisk) with epithelium Figure II-2-15.containing Terminal bronchiole lumen with epithelium containciliated cells and(asterisk) Clara cells (arrows) ing ciliated cells and Clara cells (arrows) The terminal bronchiole is the last conducting bronchiole. This bronchiole is followed by respiratory bronchioles which are periodically interrupted by alveoli in their walls. The goblet cells are absent from the epithelial lining of the respiratory bronchioles; however, this epithelium is still lined with a sparse ciliated cuboidal epithelium which prevents the movement of mucous into the alveoli. After the last respiratory bronchiole, the wall of the airway disappears and air enters the alveoli. ALVEOLAR DUCTS, ALVEOLAR SACS, AND THE ALVEOLI The alveolar ducts and sacs have little or no walls and consist almost entirely of alveoli. The alveoli constitute 80–85% of the volume of the normal lung. There are 300 million alveoli in the lungs, each ~200 microns in diameter. The cuboidal epithelium of the respiratory bronchioles and the alveolar ducts are continuous with the squamous cells lining the alveoli. 56 USMLE Step 1 Anatomy.indb 56 9/15/17 10:51 AM Chapter 2 Thorax Alveolar macrophage Type I cell Alveolus Alveolar macrophage l Connective tissue Surfactant Type II cells Capillary Red blood cell Alveolus Endothelial cell Type I cell Basal lamina Endothelial cell Capillary Figure II-2-16. Alveolus andand Blood–Air Barrier Figure II-2-16. Alveolus blood–air barrier The type I pneumocyte is the major cell lining cell of the alveolar surfaces (also called small alveolar cell or alveolar type I cell). • Represent only 40% of the alveolar lining cells, but are spread so thinly they cover 90–95% of the surface • Primarily involved in gas exchange • Post-mitotic The type II pneumocyte is the other major alveolar cell (also called great alveolar cell [because of its size], granular pneumocyte, septal cell, corner cell, niche cell, or alveolar type II). • Constitute 60% of the cell lining the alveoli, but form only 5–10% of the surface • Produce and secrete surfactant • Large, round cells with “myelin figures” in their apical cytoplasm which represent the remnants of surfactant after histological processing • Serve as stem cells for themselves and the type I cell 57 USMLE Step 1 Anatomy.indb 57 9/15/17 10:51 AM Part II l Gross Anatomy Anatomy Immunology Pharmacology Biochemistry Physiology Medical Genetics Pathology Behavioral Science/Social Sciences Copyright McGraw-Hill Companies. Used with permission. Copyright McGraw-Hill Companies. Used with permission. Microbiology Figure II-2-17. Alveoli with type I pneumocytes (arrowhead), type II Figure II-2-17. Alveoli with Type I Pneumocytes (arrowhead), Type II Pneumopneumocytes (arrow), and alveolar macrophage (curved arrow) cytes (arrow), and Alveolar Macrophage (curved in the alveolar wall.arrow) in the Alveolar Wall Surfactant Clinical Correlate Corticosteroids induce the fetal synthesis of surfactant. High insulin levels in diabetic mothers antagonize the effects of corticosteroids. Infants of diabetic mothers have a higher incidence of respiratory distress syndrome. Surfactant is essential to maintain the normal respiratory mechanics of the alveoli. Production of surfactant in the fetus is essential for the survival of the neonate as it takes its first breath. Surfactant is composed of a mixture of phospholipids and surfactant proteins whose function is to aid in the spreading of the surfactant at the alveolar air–water interface. The phospholipids act as a detergent which lowers the surface tension of the alveoli and prevents alveolar collapse during expiration. Most surfactant is recycled back to Type II cells for reutilization; some of it undergoes phagocytosis by macrophages. Alveolar Wall In the alveolar wall under the alveolar epithelium is a rich network of capillaries arising from pulmonary arteries. The alveolar wall contains a variety of cells and extracellular fibers. The cells include fibroblasts, macrophages, myofibroblasts, smooth-muscle cells, and occasional mast cells. Type I and II collagens, as well as elastic fibers, are in the septa. Type I collagen is present primarily in the walls of the bronchi and bronchioles. Twenty percent of the mass of the lung consists of collagen and elastic fibers. Elastic fibers are responsible for the stretching and recoiling activities of the alveoli during respiration. These microscopic elements are responsible for the recoil of the lungs during expiration. Gas exchange occurs between capillary blood and alveolar air across the blood– gas barrier. This barrier consists of surfactant, the squamous Type I pneumocytes, a shared basal lamina, and capillary endothelium. The distance between the lumen of the capillary and the lumen of the alveolus can be as thin as 0.1 microns. There are openings in the wall of most alveoli that form the pores of Kohn. These pores are thought to be important in collateral ventilation. The diameter of these alveolar pores can be as large as 10 to 15 microns. 58 USMLE Step 1 Anatomy.indb 58 9/15/17 10:51 AM Chapter 2 l Thorax Alveolar Macrophages Clinical Correlate The alveolar macrophages are derived from monocytes that exit the blood vessels in the lungs. The resident alveolar macrophages can undergo limited mitoses to form additional macrophages. These cells can reside in the interalveolar septa as well as in the alveoli. Alveolar macrophages that patrol the alveolar surfaces may pass through the pores of Kohn. Alveolar macrophages have several other names: dust cells because they have phagocytosed dust or cigarette particles, and heart failure cells because they have phagocytosed blood cells that have escaped into the alveolar space during congestive heart failure. There are ~1–3 macrophages per alveolus. Alveolar macrophages vary in size, 15–40 microns in diameter. These macrophages represent the last defense mechanism of the lung. Macrophages can pass out of the alveoli to the bronchioles and enter the lymphatics or become trapped in the moving mucous layer and propelled toward the pharynx to be swallowed and digested. EMBRYOLOGY OF THE HEART Formation of Heart Tube The heart begins to develop from splanchnic mesoderm in the latter half of week 3 within the cardiogenic area of the cranial end of the embryo. Neural crest cells migrate into the developing heart and play an important role in cardiac development. The cardiogenic cells condense to form a pair of primordial heart tubes which will fuse into a single heart tube during body folding. • The heart tube undergoes dextral looping (bends to the right) and rotation. • The upper truncus arteriosus (ventricular) end of the tube grows more rapidly and folds downward and ventrally and to the right. • The atria and sinus venosus lower part of the tube fold upward and dorsally and to the left. These foldings begin to place the chambers of the heart in their postnatal anatomic positions. The primitive heart tube forms 4 dilatations and a cranial outflow tract, the truncus arteriosus. The fates of these are shown below. Arterial (outflow) Truncus arteriosus Blood flow Bulbus cordis Ventral Dorsal Primitive ventricle Atria Primitive atrium Sinus venosus Venous (Inflow) Ventricles Figure II-2-18. Development of the Heart Tube Figure II-2-18. Development of the Heart Tube 59 USMLE Step 1 Anatomy.indb 59 9/15/17 10:51 AM Part II Anatomy Pharmacology l Gross Anatomy Immunology Table II-2-2. Adult Structures Derived From the Dilatations of the Primitive Heart Embryonic Dilatation Adult Structure Truncus arteriosus (neural crest) Aorta; Pulmonary trunk; Semilunar values Biochemistry Bulbus cordis Smooth part of right ventricle (conus arteriosus) Smooth part of left ventricle (aortic vestibule) Physiology Primitive ventricle Medical Genetics Trabeculated part of right ventricle Trabeculated part of left ventricle Primitive atrium* Pathology Microbiology Trabeculated part of right atrium (pectinate