Kaplan USMLE Step 1 Lecture 2018 - ANATOMY PDF

www.ebook2book.ir  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...

www.ebook2book.ir  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. www.ebook2book.ir  STEP 1 ® USMLE Lecture Notes 2018 Anatomy www.ebook2book.ir USMLE Step 1 Anatomy.indb 1 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. 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For more information or to purchase books, please call the Simon & Schuster special sales department at 866-506-1949. www.ebook2book.ir 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 www.ebook2book.ir USMLE Step 1 Anatomy.indb 3 9/15/17 10:50 AM www.ebook2book.ir  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 www.ebook2book.ir 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 www.ebook2book.ir USMLE Step 1 Anatomy.indb 6 9/15/17 10:50 AM  PART I Early Embryology and Histology: Epithelia www.ebook2book.ir USMLE Step 1 Anatomy.indb 1 9/15/17 10:50 AM www.ebook2book.ir  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 tes- ticular 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 migrat- ing 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 www.ebook2book.ir USMLE Step 1 Anatomy.indb 3 9/15/17 10:50 AM  Part I l Early Embryology and Histology: Epithelia Anatomy Immunology 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. Pharmacology Biochemistry MIF: Müllerian-inhibiting factor TDF: testis-determining factor Primordial Physiology Medical Genetics germ cells Yolk sac Urogenital ridge Pathology Behavioral Science/Social Sciences Mesonephric duct (Wolffian) MIF: Müllerian-inhibiting factor Paramesonephric duct TDF: testis-determining factor (Müllerian) Microbiology Indifferent gonad TDF Testosterone No factors MIF Testis Ovary and male and female genital system 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 www.ebook2book.ir USMLE Step 1 Anatomy.indb 4 9/15/17 10:50 AM  Chapter 1 l Gonad Development Type B Spermatogonia (46, 2n) (Diploid) Oogonia Meiosis I Primary spermatocyte DNA replication Primary (46, 4n) oocyte Synapsis Crossover Cell division Alignment and disjunction Centromeres do not split Secondary spermatocyte (23, 2n) Secondary oocyte Meiosis II Cell division Alignment and disjunction Centromeres split Gamete (23, 1n) (Haploid) Figure I-1-2. Meiosis Figure I-1-2. Meiosis 5 www.ebook2book.ir USMLE Step 1 Anatomy.indb 5 9/15/17 10:50 AM  Part I l Early Embryology and Histology: Epithelia Anatomy Immunology SPERMATOGENESIS At week 4, primordial germ cells arrive in the indifferent gonad and remain dormant until puberty. Pharmacology Biochemistry 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. Type B spermatogonia enter meiosis I to form primary spermatocytes. Physiology Medical Genetics Primary spermatocytes form 2 secondary spermatocytes. Secondary spermatocytes enter meiosis II to form 2 spermatids. Spermatids undergo spermiogenesis, which is a series of morphologi- Pathology Behavioral Science/Social Sciences cal changes resulting in the mature spermatozoa. Microbiology OOGENESIS At week 4, primordial germ cells arrive in the indifferent gonad and differ- entiate 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 second- ary 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 www.ebook2book.ir 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 ❏❏ Demonstrate understanding of the formation of the bilaminar I 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 e: mito g va lea C Day 2 Day 3 Embryoblast (forms embryo) 2-cell Blastula 4-cell Blastula Day 4 Trophoblast (forms placenta) Morula Day 5 (46, 2N) Zygote Blastocyst Day 1 Fertilization Day 6 (Implantation begins) Ovary Zona Corona Cytotrophoblast pellucida radiata cells Ampulla Blastocyst cavity of oviduct Embryoblast Secondary oocyte arrested in metaphase of meiosis II Syncytiotrophoblast FigureFigure I-2-1. Week I-2-1.1Week 1 7 www.ebook2book.ir USMLE Step 1 Anatomy.indb 7 9/15/17 10:50 AM  Part I l Early Embryology and Histology: Epithelia Anatomy Immunology Prior to fertilization, spermatozoa undergo 2 changes in the female genital tract: Capacitation consists of the removal of several proteins from the plasma membrane of the acrosome of the spermatozoa. It occurs over Pharmacology Biochemistry about 7 hours in the female reproductive tract. Hydrolytic enzymes are released from the acrosome used by the sperm to penetrate the zona pellucida. This results in a cortical reaction that prevents other spermatozoa penetrating the zona pellucida thus pre- venting polyspermy. Physiology Medical Genetics 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 Pathology Behavioral Science/Social Sciences 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, form- ing 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 www.ebook2book.ir USMLE Step 1 Anatomy.indb 8 9/15/17 10:50 AM  Chapter 2 l First 8 Weeks of Development Hypoblast Bilaminar disk Epiblast Endometrial blood vessel Lacuna spaces Endometrial gland Syncytiotrophoblast Prechordal Implantation plate hCG Chorionic cavity Connecting Yolk sac stalk Amniotic cavity Primary villi Chorion Extraembryonic mesoderm Cytotrophoblast FigureI-3-1. Figure I-2-2.Week Week22 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 www.ebook2book.ir USMLE Step 1 Anatomy.indb 9 9/15/17 10:50 AM  Part I l Early Embryology and Histology: Epithelia Anatomy Immunology Clinical Correlate Human chorionic gonadotropin (hCG), a glycoprotein produced by the syncytiotrophoblast, stimulates progesterone production by the corpus luteum. hCG can Pharmacology Biochemistry 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 H  igh hCG level may predict a multiple pregnancy, hydatidiform mole, or gestational trophoblastic disease. Pathology Behavioral Science/Social Sciences WEEKS 3–8: EMBRYONIC PERIOD All major organ systems begin to develop during the weeks 3–8. By the end of this Microbiology 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 Hypoblast Endoderm B Figure I-4-1. Week Figure 3 I-2-3. Week 3 10 www.ebook2book.ir 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 www.ebook2book.ir USMLE Step 1 Anatomy.indb 11 9/15/17 10:50 AM  Part I l Early Embryology and Histology: Epithelia Anatomy Immunology Table I-2-1. Germ Layer Derivatives Ectoderm Mesoderm Endoderm Surface ectoderm Muscle Forms epithelial lining of: Pharmacology Biochemistry Epidermis Smooth GI track: foregut, midgut, and Hair Cardiac hindgut Nails Skeletal Lower respiratory system: larynx, trachea, bronchi, and lung Physiology Inner ear, external ear Medical Genetics Connective tissue Genitourinary system: urinary Enamel of teeth All serous membranes bladder, urethra, and lower vagina Lens of eye Bone and cartilage Pharyngeal pouches: Anterior pituitary (Rathke’s pouch) Blood, lymph, cardiovascular organs Pathology Behavioral Science/Social Sciences Auditory tube and middle ear Parotid gland Adrenal cortex Palatine tonsils Anal canal below Gonads and internal reproductive Parathyroid glands pectinate line organs Spleen Thymus Microbiology Neuroectoderm Kidney and ureter Forms parenchyma of: Neural tube Dura mater Liver Central nervous system Retina and optic nerve Notochord Pancreas Pineal gland Nucleus pulposus S  ubmandibular and sublingual glands Neurohypophysis Follicles of thyroid gland Astrocytes 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 www.ebook2book.ir USMLE Step 1 Anatomy.indb 12 9/15/17 10:50 AM  Histology: Epithelia 3 Learning Objectives ❏❏ Demonstrate understanding of epithelial cells ❏❏ Use knowledge of epithelium I ❏❏ 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, tis- sues form organs, organs form organ systems, and systems make up the organ- ism. 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 histol- ogy 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, anti- bodies, 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 tra- chea, bronchi, intestine, and pancreatic ducts transport chloride from baso- lateral surface to lumen via pumps in the basolateral surface and channels in 13 www.ebook2book.ir USMLE Step 1 Anatomy.indb 13 9/15/17 10:50 AM  Part I l Early Embryology and Histology: Epithelia Anatomy Immunology 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. Pharmacology Biochemistry 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 Physiology Medical Genetics 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 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 trans- port solutes from one side of the barrier to the other. Microbiology 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 ei- ther 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 www.ebook2book.ir USMLE Step 1 Anatomy.indb 14 9/15/17 10:50 AM  Chapter 3 l Histology: Epithelia Copyright CopyrightMcGraw-Hill McGraw-HillCompanies. Used Companies. with Used permission. with permission. Figure FigureI-5-1. I-3-1.Kidney tubule simple Kidney tubule simple cuboidal cuboidal epithelium epithelium(arrow) (arrow) stained stainedwith withH&E, H&E, L-lumen L-lumen Eosin is a pink-to-orange dye which stains acidophilic substrates such as ba- sic 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 Copyright McGraw-Hill Companies. Companies.Used with Used permission. with permission. FigureI-3-2. Figure I-5-2.Small SmallIntestine Intestine Simple Simple Columnar Columnar Epithelium Epithelium Enterocytes(arrow), Enterocytes (arrow),Goblet Goblet cells cells (arrowhead) (arrowhead) 15 www.ebook2book.ir USMLE Step 1 Anatomy.indb 15 9/15/17 10:50 AM  Part I l Early Embryology and Histology: Epithelia Anatomy Immunology 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. Pharmacology Biochemistry Physiology Medical Genetics Pathology Behavioral Science/Social Sciences Microbiology Copyright McGraw-Hill Copyright McGraw-Hill Companies. Companies.Used with Used permission..with permission. Figure Figure I-5-3. Kidneysimple I-3-3. Kidney simplesquamous squamousepithelium epithelium(arrows), (arrows), simple cuboidal epithelium simple cuboidal epithelium (arrowheads) (arrowheads) Pseudostratified columnar epithelium is found in the nasal cavity, trachea, bronchi, and epididymis. Copyright McGraw-Hill Copyright McGraw-HillCompanies. Companies.Used Usedwith withpermission. permission. Figure FigureI-5-4. I-3-4. Trachea pseudostratifiedcolumnar Trachea pseudostratified columnarepithelium epitheliumwith with true cilia (arrow) and goblet cells (arrowhead), basement true cilia (arrow) and goblet cells (arrowhead), basement membrane (curved arrow) membrane (curved arrow) 16 www.ebook2book.ir 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 Copyright McGraw-Hill Companies. Companies.Used with Used permission. with permission. Figure I-5-5. Bladder Figure I-3-5. BladderTransitional TransitionalEpithelium Epithelium Stratified squamous epithelium is found in the oral cavity, pharynx, and esophagus (non-keratinized) and in the skin (keratinizing). Copyright McGraw-Hill Copyright McGraw-HillCompanies. Companies.Used Usedwith permission. with permission. Figure FigureI-5-6. I-3-6.Stratified Stratified Squamous Epithelium(Thick Squamous Epithelium (ThickSkin) Skin) (1)(1)stratum stratumbasale basale(2) (2)stratum stratum spinosum spinosum (3)(3) stratum stratum granulosum granulosum (4) (4)stratum stratum lucidum lucidum (5) (5) stratum corneum stratum 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 www.ebook2book.ir 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 Copyright McGraw-Hill Companies. Companies.Used with Used permission. with permission. Microbiology FigureI-3-7. Figure I-5-7.Ducts Ductsofof salivary salivary gland gland with with stratified stratified cuboidalepithelium cuboidal epitheliumsmall smallblood bloodvessels vessels with with endotheliumand endothelium andsmooth smoothmuscle muscle(arrows) (arrows) 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 Copyright McGraw-HillCompanies. Companies.Used Usedwith withpermission. permission. Figure I-5-8.Submandibular Figure I-3-8. SubmandibularGland gland This gland Mixed is a mixed salivary glandsalivary glandacini with mucous with (arrow) mucus andacinidarker (arrow) and darker staining serous acini; small blood vessels (arrowheads) staining serous acini; small blood vessels (arrowheads) 18 www.ebook2book.ir 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 polymeriza- tion 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 mo- tile 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 Clinical Correlate Intermediate filaments are 10-nm-diameter filaments that are usually stable once A first step in the invasion of malignant formed. These filaments provide structural stability to cells. There are 4 types: cells through an epithelium results Type I: keratins (keratins are found in all epithelial cells) from a loss of expression of cadherins that weakens the epithelium. Type II: intermediate filaments comprising a diverse group –– Desmin is found in skeletal, cardiac, and GI tract smooth muscle cells. Clinical Correlate –– Vimentin is found in most fibroblasts, fibrocytes, endothelial cells, Changes in intermediate filaments and vascular smooth muscle. are evident in neurons in Alzheimer’s –– Glial fibrillary acidic protein is found in astrocytes and some disease and in cirrhotic liver diseases. 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 intra- cellular transport of vesicles and molecules. Such transport exists in all cells but Clinical Correlate is particularly important in axons. Transport requires specific ATPase motor Colchicine prevents microtubule molecules; dynein drives retrograde transport and kinesin drives anterograde transport. polymerization and is used to prevent neutrophil migration in gout. Microtubules are found in true cilia and flagella, and utilize dynein to convey Vinblastine and vincristine are used motility to these structures. Microtubules form the mitotic spindle during in cancer therapy because they inhibit mitosis and meiosis. the formation of the mitotic spindle. 19 www.ebook2book.ir USMLE Step 1 Anatomy.indb 19 9/15/17 10:51 AM  Part I l Early Embryology and Histology: Epithelia Anatomy Immunology 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 adhe- Pharmacology Biochemistry sion 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). Physiology Medical Genetics 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 Pathology Behavioral Science/Social Sciences transmembrane surface molecules with extracellular domains that bind to fi- bronectin and laminin, which are components of extracellular basement mem- brane. The cytoplasmic portions of integrins bind to actin filaments. Integrins form a portion of hemidesmosomes but are also important in interactions be- tween leukocytes and endothelial cells. Microbiology CELL SURFACE SPECIALIZATIONS Cell Adhesion A cell must physically interact via cell surface molecules with its external Clinical Correlate environment, whether it be the extracellular matrix or basement membrane. Pemphigus Vulgaris The basement membrane is a sheet-like structure underlying virtually all epithelia, which consists of basal lamina (made of type IV collagen,  Autoantibodies against glycoproteins [e.g., laminin], and proteoglycans [e.g., heparin sulfate]), and desmosomal proteins in skin cells reticular lamina (composed of reticular fibers). Cell junctions anchor cells to  Painful flaccid bullae (blisters) in each other, seal boundaries between cells, and form channels for direct transport oropharynx and skin that rupture and communication between cells. The 3 types of junctional complex include easily anchoring, tight, and gap junctions.  Postinflammatory hyperpigmentation Cell Junctions Treatment: corticosteroids Tight junctions (zonula occludens) function as barriers to diffusion and determine cell polarity. They form a series of punctate contacts of adjacent Bullous Pemphigoid epithelial cells near the apical end or luminal surface of epithelial cells. The  Autoantibodies against major components of tight junctions are occludens (ZO-1,2,3) and claudin basement-membrane proteins. These proteins span between the adjacent cell membranes and their hemidesmosomal proteins cytoplasmic parts bind to actin microfilaments.  Widespread blistering with Zonula adherens forms a belt around the entire apicolateral circumference of pruritus the cell, immediately below the tight junction of epithelium. Cadherins span between the cell membranes. Like the tight junctions immediately above them,  Less severe than pemphigus the cytoplasmic parts of cadherins are associated with actin filaments. vulgaris Desmosomes (macula adherens) function as anchoring junctions. Desmo- Rarely affects oral mucosa somes provide a structural and mechanical link between cells. Cadherins span  Can be drug-induced (e.g., between the cell membranes of desmosomes and internally desmosomes are middle-aged or elderly patient on anchored to intermediate filaments in large bundles called tonofilaments. multiple medications) Hemidesmosomes adhere epithelial cells to the basement membrane. The base- Treatment: corticosteroids ment membrane is a structure that consists of the basal membrane of a cell 20 www.ebook2book.ir 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 reticu- lar 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, com- posed of reticular fibers. Through the binding of extracellular components of hemidesmosomes to inte- grins, 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 em- bryogenesis, and cell invasion by malignant neoplasms. Gap junctions (communicating junctions) function in cell-to-cell communi- cation between the cytoplasm of adjacent cells by providing a passageway for ions such as calcium and small molecules such as cyclic adenosine monophos- phate (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 junc- tions, gap junctions are not associated with any cytoskeletal filament. Apical surface Microvilli Plasma membrane Tight Actin microfilaments junction Intermediate filaments Zonula (keratin) adherens Desmosome Gap junction Cell A Cell B Cell C Cell D Hemidesmosome Basal lamina Figure I-5-9.Junctions Figure I-3-9. Junctions 21 www.ebook2book.ir USMLE Step 1 Anatomy.indb 21 9/15/17 10:51 AM  Part I l Early Embryology and Histology: Epithelia Anatomy Immunology Sealing strands of tight junction Pharmacology Biochemistry Physiology Medical Genetics Pathology Behavioral Science/Social Sciences Microbiology Copyright Lippincott Copyright Williams Lippincott & Wilkins. Williams Used with & Wilkins. Usedpermission. with permission. Figure I-5-10. Freeze-fracture of tight junction Figure I-3-10. Freeze-fracture of Tight Junction Connexon ce l a r spa A t r a cellu of cell I n e r bilay 2–4 nm Lipid cell B y e r of bila ce Lipid l a r spa cellu Intra 1.5 nm 7 nm Figure Figure I-5-11. I-3-11. Gap junction 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 epi- thelial 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 www.ebook2book.ir 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. FigureApical CellApical I-5-12. Surface/Cell Junctions junctions cell surface/cell Cilia Clinical Correlate Cilia contain 9 peripheral pairs of microtubules and 2 central microtubules. The Kartagener syndrome is characterized microtubules convey motility to cilia through the ATPase dynein. Cilia bend by immotile spermatozoa and and beat on the cell surface of pseudostratified ciliated columnar respiratory infertility. It is due to an absence of epithelial cells to propel overlying mucous. They also form the core of the fla- dynein that is required for flagellar gella, the motile tail of sperm cells. 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 Copyright LippincottWilliams Williams& Wilkins. Used & Wilkins. withwith Used permission. permission. Figure I-5-13. Cilia Figure I-3-13. Cilia 23 www.ebook2book.ir USMLE Step 1 Anatomy.indb 23 9/15/17 10:51 AM  Part I l Early Embryology and Histology: Epithelia Anatomy Immunology Dynein arms B A Pharmacology Biochemistry 1 Nexin link 2 Spoke 9 3 Physiology Medical Genetics 8 Central 4 singlet 7 Pathology Behavioral Science/Social Sciences 5 6 Plasma membrane Microbiology Central sheath Bridge Figure FigureI-5-14. I-3-14.Structure Structure of of the