NBME PATHOLOGY FINAL TEST BANK EXAM NEWEST ACTUAL EXAM COMPLETE QUESTIONS AND CORRECT DETAILED ANSWERS

NBME PATHOLOGY FINAL TEST BANK EXAM NEWEST ACTUAL EXAM COMPLETE QUESTIONS AND CORRECT DETAILED ANSWERS Apoptosis: Programmed cell death. REQUIRES ATP. Can occur via the intrinsic or extrinsic pathways, both of which involve activation of cytosolic caspases which mediate cellular breakdown. **Unlike necrosis, apoptosis does not involve significant inflammation. Involves eosinophilic cytoplasm, cell shrinkage, pyknosis and basophilia, membrane blebbing and karyorrhexis, and formation of apoptotic bodies which are phagocytosed. DNA laddering is a sensitive indicator of apoptosis* Occurs because during karyorrhexis endonucleases yield 180bp fragments. Radiation therapy does what? Causes apoptosis of cancer cells because it causes formation of free radicals which lead to dsDNA breakage. rapidly dividing cells like skin and GI mucosa are highly susceptible to radiation-induced apoptosis. Intrinsic pathway of apoptosis: what is its general purpose / when does it occur? It's involved in tissue remodeling in embryogenesis. Often occurs when a regulating factor is withdrawn from a proliferating cell population. For example, low IL-2 after completion of an immunological reaction causes apoptosis of proliferating effector cells. Also occurs in response to injury from radiation, toxins, hypoxia,etc. Changes in proportions of pro- and anti-apoptotic factors leads to an increase in mitochondrial permeability and cyt c release. BAK, BAX, Bcl-2: Which of these are pro- and which are anti-apoptotic? BAX and BAK are pro. Bcl-2 is anti-apoptotic. How does Bcl-2 function? It prevents cyt c release by binding to an inhibiting Apaf-1, which normally INDUCES caspases. What happens if Bcl-2 is overexpressed? This occurs in follicular lymphoma. Apaf-1 is over-inhibited which leads to tumorigenesis because of lowered caspase activation. Extrinsic pathway of apoptosis: 2 basic pathways? 1. Ligand receptor interactions. FasL binding to Fas (CD95). 2. Immune cell-->cytotoxic T-cell release of perforin and granzyme B. Where is Fas-FasL interaction required? In thymic medullary negative selection. Mutations in Fas increases the numbers of circulating self-reactive lymphocytes due to failure of clonal deletion. *Defective fas-fasL interactions is the basis of autoimmune disorders* How does Fas initiate cell death? After it crosslinks with FasL, multiple Fas molecules coalesce. This makes a binding site for a death domain. Necrosis: Exogenous injury causes enzymatic degradation and protein denaturation of a cell. IC components extravasate. *There's an inflammatory process unlike apoptosis* Coagulative necrosis occurs in the: Caused by ischemia or infarction typically. heart, liver, kidney. Occurs in tissues supplied by end arteries. High cytoplasmic binding of acidophilic dye. Proteins denature first followed by enzymatic degradation. Liquefactive necrosis occurs in the: brain, bacterial abscess and pleural effusion. Occurs in CNS because of high fat content there. Unlike coag necrosis, enzymatic degradation due to release of lysosomal enzymes occurs first. Caseous necrosis: TB, systemic fungi, Nocardia. Tissue maintains a cheese-like appearance. Tissue is a proteinaceous dead cell mass. Fatty necrosis: Enzymatic--Pancreas. Saponification. Released fatty acids interact with calcium to form soaps. Calc deposits appear dark on staining. Nonenzymatic--breast trauma. Fibroid necrosis: Occurs in blood vessels. Henoch-Schonlein purpura, Churg-Strauss syndrome. Malignant hypertension. Accumulation of amorphous, basic proteinaceous substances resembling fibrin. Gangrenous necrosis: Dry (ischemic coagulative) and wet (infection). Common in limbs and GI tract. Reversible cell injury with O2: low ATP synthesis, cellular swelling because with no ATP there's impaired Na/K pump. Nuclear chromatin clumping. Low glycogen. Fatty change. Ribosomal detachment (low protein synthesis). Irreversible cell injury: nuclear pyknosis, karyolysis and karyorrhexis. Ca2+ influx--> caspase activation. PM damage. lysosomal rupture. mitochondrial permeability. Areas of the brain susceptible to ischemia: ACA / MCA / PCA boundary areas. The watershed areas, or border zones, receive dual blood supply from most distal branches of two arteries. However, systemic hypoperfusion may cause ischemia in these areas. **Hypoxic ischemic encephalopathy affects pyramidal cells of the hippocampus and Purkinjie cells of the cerebellum. Areas of heart: Subendocardium (LV) Areas of kidney: Straight segment of the proximal tubule (medulla) and thick ascending loop (medulla). Areas of liver: Area around central vein (zone III) Areas of colon: splenish flexure, colon Red infarct: Occur in loose tissues with multiple blood supplies such as liver, lung, intestines. Pale infarcts: Occur in solid tissues with a single blood supply such as heart, kidney and spleen. What is the first sign of shock? tachycardia. Shock in the setting of DIC (disseminated intravascular coagulation) secondary to trauma is likely due to... ?