USMLE STEP I Review Week 1: Cell Bio & Histology

1. Chase Findley, MSIV USMLE STEP I Review Week 1: Cell Bio & Histology

2. Basic Cell Biology

3. Cell Cycle Phases • Checkpoints control transitions between cell phases. Regulated by cyclins, cdks, and tumor suppressors.

4. Cell Cycle Phases • Permanent cells • Remain in G0, regenerate from stem cells • Neurons, skeletal and cardiac muscle, RBC’s • Stable cells • Enter G1 from G0 when stimulated • Hepatocytes, lymphocytes • Labile cells • Never go to G0, divide rapidly with short G1 • Bone marrow, gut epithelium, skin, hair follicles

5. Plasma Membrane Composition • Asymmetric fluid bi-layer • 50% cholesterol, 50% phospholipids • Small amounts of protein, sphingolipids, glycolipids • High cholesterol or long saturated fatty acid content increases melting temperature

6. Endoplasmic Reticulum • Rough • Site of synthesis of secretory (exported) proteins and N-linked oligosaccharide addition • In neurons, (Nissl bodies) synthesize enzymes and peptide neurotransmitters • Mucous secreting goblet cells and antibody secreting plasma cells are rich in RER

7. Rough Endoplasmic Reticulum

8. Endoplasmic Reticulum • Smooth • Site of synthesis of steroids • Detoxification of drugs and poisons • Liver hepatocytes and adrenal cortex are rich in SER

9. Smooth Endoplasmic Reticulum

10. Golgi Apparatus • “Distribution center” of proteins and lipids from ER to plasma membrane, lysosomes, secretory vesicles • Adds mannose-6-phosphate to proteins, targeting to lysosome • Failure results in I-cell disease, enzymes secreted outside cell • Proteoglycan assembly and sulfation

11. Golgi Apparatus

12. Microtubules • Helical array of polymerized dimers of α and β tubulin • Each dimer has 2 GTP bound • Incorporated into flagella, cilia, mitotic spindles, neurons • Chediak-Higashi syndrome • Defect in microtubule polymerization with decreased phagocytosis • Target of mebendazole, taxol, griseofulvin, vincristine, vinblastine, colchicine

13. Cilia Structure • 9+2 arrangement of microtubules • Dynein (ATPase) links peripheral 9 doublets, causes bending by differential sliding of doublets • Dynein=retrograde Kinesis=anterograde • Kartagener’s syndrome • Dynein defect, immotile cilia, infertility, recurrent infections

14. Collagen • Most abundant protein in body • Organizes, strengthens extracellular matrix • Type I • Bone, skin, tendon, dentin, fascia, cornea • Type II • Cartilage, vitreous body, nucleus pulposus • Type III (Reticulin) • Skin, blood vessels, uterus, fetal tissue • Type IV • Basement membrane

15. Collagen Synthesis • Inside fibroblasts • Synthesis (RER) • Translation of collagen α-chains (preprocollagen) • Hydroxylation (ER) • Specific proline and lysine residues, requires Vitamin C • Glycosylation (Golgi) • Pro-α chain residues, formation of procollagen (triple helix of α-chains) • Exocytosis • Procollagen exocytosed to extracellular space

16. Collagen Synthesis • Outside fibroblasts • Proteolytic processing • Cleavage of terminal regions of procollagen, transforms into insoluble tropocollagen • Cross-linking • Reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross-linkage, produces collagen fibrils • Defective collagen synthesis causes Ehlers-Danlos syndrome.

17. Elastin • “Stretchy” protein • Rich in proline, lysine • Found in lungs, large arteries, elastic ligaments • α-1 antitrypsin inhibits elastase, excessive elastase activity causes emphysema

18. Phosphotidylcholine (Lecithin) Function • Major component of RBC membranes, surfactant, myelin, bile • Used in esterification of cholesterol

19. Immunohistochemical Stains • Connective Tissue • Muscle • Epithelial Cells • Neurons • Neuroglia • Vimentin • Desmin • Cytokeratin • Neurofilaments • Glial fibrillary acid proteins

20. Gastrointestinal Histology

21. Digestive Tract Histology • Mucosa • Contains epithelium, lamina propria, muscularis mucosa • Absorptive function, villae • Submucosa • Contains submucosal nerve plexus • Muscularis externa • Contains Myenteric nerve plexus • Inner circular, outer longitudinal • Serosa/adventitia

22. Digestive Tract Histology • Submucosal nerve plexi • Submucosal layer • Coordinates secretions, blood flow, absorption • Myenteric nerve plexi • Muscularis externa layer • Coordinates motility

23. Digestive Tract Histology • Brunner’s Glands • Located in duodenal submucosa • Secrete alkaline mucous, neutralize acidic stomach contents • Hypertrophy in peptic ulcer disease

24. Digestive Tract Histology • Peyer’s Patches • Unencapsulated lymph tissue in mucosa and submucosa of small intestine • Take up antigen, stimulate local B cells to differentiate into IgA-secreting plasma cells • IgA secreted into lumen

25. Digestive Tract Histology • Barrett’s Esophagus • Replacement of non-keratinized, squamous epithelium with intestinal columnar epithelium in distal esophagus • Caused by acid reflux, may lead to adenocarcinomas • Example of metaplasia

26. Liver Histology • Zone 1 • Periportal • Sensitive to toxicinjury • Zone 2 • intermediate • Zone 3 • Pericentral • Sensitive to ischemic injury

27. GI Secretory Cells (More thoroughly covered in GI session) • Parietal Cells (Stomach) • Intrinsic factor • B12 absorption, destroyed in pernicious anemia • Gastric acid (HCl) • Chief Cells • Pepsin • Protein digestion • Mucosal Cells • Bicarbonate • G Cells • Gastrin

28. Hematological Histology

29. Erythrocytes • Anucleate • Biconcave • High surface area to volume ratio for easy gas exchange • Life span: 120 days • Glucose energy source • 90% anaerobically degraded to lactate • Membrane contains chloride-bicarbonate antiport, involved in “physiologic chloride shift”

30. Erythrocytes • Anisocytosis • Varying size • Poikilocytosis • Varying shape • Reticulocyte • Immature erythrocyte • Larger, bluish tinge

31. Neutrophils • Multilobed nucleus • Mediate acute inflammatory response • Phagocytic • Primary granules contain hydrolytic enzymes, lysozyme, myeloperoxidase • Hypersegmented in B12/folate deficiency

32. Neutrophils • Normal • Hypersegmented

33. Leukocytes • Granulocytes • Basophils, eosinophils, neutrophils • Mononuclear cells • Lymphocytes, monocytes

34. Lymphocytes • Round, densely staining nucleus • Little cytoplasm • T & B lymphocytes

35. T Lymphocytes • Mediate cellular immune response • Originate from stem cells in bone marrow, mature in thymus • Differentiate into: • Cytotoxic T cells • MHC I, CD8 • Helper T cells • MHC II, CD4 • Suppressor T Cells

36. B Lymphocytes • Mediate humoral immune response • Originate from stem cells in bone marrow, mature in marrow • Migrate to peripheral lymph tissue • Differentiate into plasma cells, produce antibody when presented with antigen • Function as APC via MHC II

37. Mast Cells • Mediate allergic reaction • Contain histamine, heparin, chemotactic factors • Bind IgE to cell membrane • Found in tissue • Cromolyn sodium prevents degranulation

38. Eosinophils

39. Monocytes • Kidney shaped nucleus • Differentiates to macrophages in tissue

40. Macrophages • Phagocytic for bacteria, cell debris, senescent blood cells • Activated by gamma interferon • Function as antigen presenting cell via MHC II

41. Plasma Cells • Off-center nucleus, clock-face chromatin • Abundant rough endoplasmic reticulum and Golgi apparatus • Differentiate from B cells, produce antibody

42. Eosinophils • Bilobate nucleus • Highly phagocytic for antigen-antibody complexes • Defend against helminth and protozoan infections • Elevated in allergies, asthma certain neoplasms, collagen vascular diseases

43. Basophils • Bilobate nucleus • Mediate allergic reaction • Contain histamine, heparin, leukotrienes • Found in blood

45. Dermatological Histology

46. Epidermal Layers *Langerhan’s cells are dendritic cells that function as APC’s in skin. Remember Birbeck granules!

47. Epithelial Cell Junctions • Zona occludens (tight junction) • Creates semi-permeable barrier • Macula adherens • Small discrete points of attachment • Gap junction • Allows adjacent cells to communicate via metabolic/electrical processes • Hemidesmosome • Anchors cells to extracellular matrix • Integrin • Maintains integrity of basement membrane

48. Epithelial Cell Junctions

49. Muscular Histology

50. Skeletal Muscle Cell Structure • Sarcomere • Skeletal muscle unit from Z line to Z line • A band • Area of overlap of actin and myosin • I band • Area of actin only Contraction causes I band shortening, A band stays same