Transcript USMLE STEP I Review Week 1: Cell Bio & Histology
Chase Findley, MSIV
Cell Cycle Phases
Checkpoints control transitions between cell phases. Regulated by cyclins, cdks, and tumor suppressors.
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
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
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
Rough Endoplasmic Reticulum
Endoplasmic Reticulum
Smooth Site of synthesis of steroids Detoxification of drugs and poisons Liver hepatocytes and adrenal cortex are rich in SER
Smooth Endoplasmic Reticulum
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
Golgi Apparatus
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
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
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
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
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.
Elastin
“Stretchy” protein Rich in proline , lysine Found in lungs, large arteries, elastic ligaments α-1 antitrypsin inhibits elastase, excessive elastase activity causes emphysema
Phosphotidylcholine (Lecithin) Function Major component of RBC membranes , surfactant , myelin , bile Used in esterification of cholesterol
Immunohistochemical Stains
Connective Tissue Muscle Epithelial Cells Neurons Neuroglia Vimentin Desmin Cytokeratin Neurofilaments Glial fibrillary acid proteins
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
Digestive Tract Histology
Submucosal nerve plexi ○ Submucosal layer ○ Coordinates secretions , blood flow, absorption Myenteric nerve plexi ○ Muscularis externa layer ○ Coordinates motility
Digestive Tract Histology
Brunner’s Glands ○ Located in duodenal submucosa ○ Secrete alkaline mucous , neutralize acidic stomach contents ○ Hypertrophy in peptic ulcer disease
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
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
Liver Histology
Zone 1 ○ Periportal ○ Sensitive to toxic injury Zone 2 ○ intermediate Zone 3 ○ Pericentral ○ Sensitive to ischemic injury
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
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”
Erythrocytes
Anisocytosis Varying size Poikilocytosis Varying shape Reticulocyte Immature erythrocyte ○ Larger, bluish tinge
Neutrophils
Multilobed nucleus Mediate acute inflammatory response Phagocytic Primary granules contain hydrolytic enzymes, lysozyme, myeloperoxidase Hypersegmented in B12/folate deficiency
Neutrophils
Normal Hypersegmented
Leukocytes
Granulocytes Basophils, eosinophils, neutrophils Mononuclear cells Lymphocytes, monocytes
Lymphocytes
Round, densely staining nucleus Little cytoplasm T & B lymphocytes
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
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
Mast Cells
Mediate allergic reaction Contain histamine, heparin, chemotactic factors Bind IgE to cell membrane Found in tissue Cromolyn sodium prevents degranulation
Eosinophils
Monocytes
Kidney shaped nucleus Differentiates to macrophages in tissue
Macrophages
Phagocytic for bacteria, cell debris, senescent blood cells Activated by gamma interferon Function as antigen presenting cell via MHC II
Plasma Cells
Off-center nucleus, clock-face chromatin Abundant rough endoplasmic reticulum and Golgi apparatus Differentiate from B cells , produce antibody
Eosinophils
Bilobate nucleus Highly phagocytic for antigen-antibody complexes Defend against helminth and protozoan infections Elevated in allergies , asthma certain neoplasms, collagen vascular diseases
Basophils
Bilobate nucleus Mediate allergic reaction Contain histamine, heparin, leukotrienes Found in blood
Epidermal Layers
*Langerhan’s cells are dendritic cells that function as APC’s in skin. Remember Birbeck granules !
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
Epithelial Cell Junctions
Skeletal Muscle Cell Structure Sarcomere Skeletal muscle unit from Z line to Z line A band Contraction causes I band shortening, A band stays same Area of overlap of actin and myosin I band Area of actin only
Skeletal Muscle Cell Structure Striated Peripheral nuclei Linear fibers
Cardiac Muscle Structure
Striated Central nuclei Branching fibers Intercalated disks Contain gap junctions which allow electrical impulse to pass between adjacent cells
Smooth Muscle
Non-striated Central, elongated nucleus “Network” muscle fibers
Neuron Structure, Schwann Cells Individual Schwann cells myelinate a single PNS axon Impulse travels via saltatory conduction
Peripheral Nerve Layers
Endoneurium Invests single nerve fiber Perineurium Surrounds a fascicle of fibers Must be rejoined for limb re attachment Epineurium Surrounds entire nerve, and associated vessels
Oligodendroglia
Each oligodendroglia myelinates multiple CNS axons Predominate glial cell in white matter Destroyed in multiple sclerosis
Microglia
CNS phagocytes Mesodermal origin (all others from ectoderm) Enlarge to large amoeboid cells in response to tissue damage Fuse into multinucleated giant cells when infected by HIV
Astrocytes
Physical support and repair of axons K+ metabolism Maintain blood-brain barrier
Sensory Corpuscles: Meissner’s Small, encapsulated nerve endings Dermis of palms, soles, digits ( hairless skin) Light discriminatory touch
Sensory Corpuscles: Pacinian
Large, encapsulated nerve endings Deep skin layers at ligaments, joint capsules, serous membranes, mesenteries Pressure, coarse touch, vibration, tension
Sensory Corpuscles: Merkel’s
Cup-shaped nerve ending Dermis of fingertips, hair follicles , hard palate Light, crude touch
Blood-Brain Barrier
Formed by: Tight junctions between nonfenestrated capillary endothelial walls Basement membrane Astrocyte foot processes
Blood-Brain Barrier
Glucose and amino acids carrier-mediated transport cross by Non-polar molecules cross more readily than polar molecules Infection destroys tight junctions, leads to vasogenic edema
Renal Structure
Glomerular Structure
Sperm Structure
Head (acrosome) Derived from Golgi apparatus Neck Contains mitochondria, energy supply from fructose Tail Derived from centrioles
Spermatogenesis
Spermatogonium Diploid, 2N Primary spermatocyte Diploid, 4N Secondary spermatocyte Haploid, 2N Spermatid Haploid, 1N Mitosis Meiosis I Meiosis II Occurs in seminiferous tubules Sertoli cells create blood-testis barrier, prevent autoimmunity
Spermatogenesis
Oogenesis
Oogenesis
Respiratory Tree
Conducting zone Warms, humidifies, filters air Smooth muscle Anatomic dead space Nose, trachea, pharynx, trachea, bronchi, bronchioles, terminal bronchioles Respiratory zone Participates in gas exchange Bronchioles, alveolar ducts, alveoli
Pneumocytes
Type I pneumocytes 97% of alveolar surface, line alveoli Responsible for gas exchange
Pneomocytes
Type II pneumocytes Secrete pulmonary surfactant Precursors to Type I and other Type II cells Proliferate during lung damage
Bronchopulmonary Segments
1 Bronchopulmonary segment has: 1 tertiary (segmental) bronchus 2 arteries (bronchial, pulmonary) Veins and lymphatics