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23 Cards in this Set
- Front
- Back
Apoptosis
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ATP required; activation of caspases; DNA laddering 180-bp; no inflammation
Intrinsic--Bcl-2 prevents cytochrome c release; dec IL-2 after completed immunological rxn triggers apoptosis Extrinsic--FAS or T-cell release of perforin & granzyme *FAS mutation-->autoreactive lymphocytes-->autoimmune disease |
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Hypoxic ischemic encephalopathy
Red neuron |
Affects pyramidal cells of hippocampus and purkinje cells of cerebellum
Red neuron: a neuron responding to irreversible injury, typically evident 12-24 hrs after injurious event; eosinophilic cytoplasm, pyknotic nucleus, loss of nissl substance |
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Areas susceptible to ischemia:
Brain Heart Kidney Liver Colon |
B: ACA/MCA/PCA boundary areas
H: subendocardium K: PCT and thick loop L: zone III (area around central vein) C: splenic flexure, rectum **CNS & neurons most susceptible; ischemia causes liquefactive necrosis and cystic astroglial scar |
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Dystrophic versus Metastatic calcification
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Dy: localized calcium deposition in tissues secondary to necrosis; pancreatic saponification, breast trauma; pts are normally normocalcemic!!
Me: widespread deposition of calcium secondary to hypercalcemia; favors kidney, lungs, and GI due to increased pH; pts are hypercalcemic |
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Axonal rxn~chromatolysis
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Seen in neural cell body following axonal injury-->increased protein synthesis and repair
Round cellular swelling Displacement of nucleus to periphery Dispersion of Nissl substance throughout cytoplasm |
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Leukocyte extravasation
Margination Tight-binding Diapedesis Migration |
Occurs at postcapillary venule
M: endothelial selectin interacts with leukocyte sialyl-lewisX protein; essentially speed bumps T: interaction btw endothelial ICAM/VCAM and leukocyte CD18/integrin/LFA-1 D: actually exits blood vessel; PECAM to PECAM M: C5a, IL-8, LTB4 are main chemotactic products |
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Free Radicals Pathologies
Radiation tx |
Retinopathy of prematurity
Bronchopulmonary dysplasia Iron overload (hemochromatosis) Reperfusion injury (ypac post tPA tx) **Acetaminophen OD (fulminant hep, renal papillary necrosis) **CCl4-->RER swelling (free radical damage)->dec protein synthesis->dec apolipoproteins-->fatty liver necrosis RTX: induces dsDNA break and forms free radicals |
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Wound healing mediators
PDGF FGF EGF TGF-b Metalloproteinases |
PDGF: secreted by activated platelets and M0's; vascular remodeling and smooth muscle recruitment
**FGF: stimulates all aspects of angiogensis EGF: stimulates cell growth via tyrosine kinase TGF-b: angiogenesis, fibrosis, cell cycle arrest **Metalloproteinases (collagenase, hydrolase): degrades collagen during tissue remodeling; **also used by invasive Ca to invade basement membrane |
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Granulomatous disease
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TH1 cells secrete IFN-g to activate M0's. TNF-a from M0's maintains granuloma formation.
Anti-TNF drugs can cause granuloma breakdown-->disseminated disease. Always screen for latent TB before starting anti-TNF tx |
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ESR elevation
Common causes |
Products of inflammation (fibrinogen) coat RBCs and cause aggregation--RBCs group (rouleax) and fall at faster rate
Anemia, infection, inflammation, cancer, pregnancy, autoimmune disorders |
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Iron poisoning
Mechanism Sx's Tx |
Iron kills cells by peroxidation of membrane lipids
n/v, gastric bleeding chelation (deferoxamine) and dialysis |
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Amyloidosis
AL (primary) AA (secondary) Dialysis-related Heritable Organ-specific |
Due to misfolded proteins; stains congo red, apple green birefringence
AL--Ig Light chain; common in multiple myeloma or other plasma cell disorder AA--acute phase reactant, seen in chronic conditions like RA D: b2-microglobulin; may present as carpal tunnel syndrome H: often due to transthyretin gene mutation-->cardiac amyloidosis and restrictive CM O: amyloid-b protein in alzheimer; amylin in DM type II |
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P-glycoprotein
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AKA multidrug resistance protein 1 (MDR1)
Expressed by some cancer cells to pump out toxins & chemotherapeutic agents. One mechanism of resistance to CTX. |
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Tumor Grade versus Stage
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G: determined by degree of cellular differentiation and mitotic activity; low grade (well differentiated), high grade (anaplastic)
S: based on site and size of primary lesion, spread to lymph nodes and mets |
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Cachexia
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Weight loss, muscle atrophy, and fatigue that occur in chronic disease (Ca, AIDS, CHF, TB). Mediated by TNF-a, IFN-g, and IL-6.
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PSaMMoma bodies
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Laminated, concentric, calcific spherules
Papillary thyroid carcinoma Serous papillary cystadenocarcinoma of ovary Meningioma Malignant mesothelioma |
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Carcinogens--
Alfatoxins (aspergillus) Alkylating agents Aromatic amines (naphthylamine) Asbestos CCL4 Cigaretter smoke |
Alf: liver-HCC
Alk: blood-leukemia, lymphoma Aro: bladder-transitional cell carcinoma Asbestos: lung-bronchogenic>mesothelioma CCL4: liver-centrilobar necrosis, fatty change Cigs: transitional CC; esophagus-squamous & adenocarcinoma; RCC; larynx-squamous; lung-squamous & small CC; pancreas-adenocarcinoma |
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Carcinogens--
Ethanol Ionizing radiation Nitrosamines (smoked foods) Vinyl chloride |
Eth: liver-HCC
Ion: thyroid-papillary thyroid carcinoma Nit: stomach-gastric Ca Vin: liver-angiosarcoma |
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Oncogenic Microbes
HBV, HCV H. pylori Liver fluke (Clonorchis sinensis) Schistosoma haematobium |
HBV, HCV--HCC
H. pylori--gastric adenocarcinoma & MALT lymphoma Clonorchis--cholangiocarcinoma, pigmented gall stones; tx praziquantel Schistosoma--bladder Ca (squamous), painless hematuria, snails are host; tx praziquantel |
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Oncogenes--
BCR-ABL bcl-2 BRAF c-kit c/n/l myc Her2-neu (c-erbB2) ras ret |
Cause gain of fxn; need to damage only 1 allele
BCR-ABL--TK; CML & ALL bcl-2--anti-apoptosis BRAF--melanoma c-kit--GIST GI stromal tumor c/n/l myc--transcription factor; burkitt, lung tumor, neuroblastoma Her2-neu (c-erbB2)--TK; breast, ovarian ras--GTPase; colon, lung, pancreatic Ca ret--TK; MEN 2A & 2B |
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Tumor suppressor genes--
APC DCC NF1 NF2 p53 Rb |
Loss of fxn; both alleles must be lost--two hits
Loss of heterogeneity--"first hit" APC: colorectal Ca (associated w/FAP) BRCA1/2: DNA repair protein DCC: deleted in colon Ca NF1: RAS GTPase activating protein NF2: merlin protein p53: Li-Fraumeni syndrome; TF for p21; blocks G1 to S Rb: retinoblastoma, osteosarcoma; inhibits E2F, blocks G1 to S |
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Tumor markers
Alkaline phosphatase AFP b-HCG CA-19-9 CA-125 CEA S-100 TRAP |
ALP: mets to bone, liner, paget disease of bone, seminoma (placental ALP)
AFP: HCC, yolk sac tumor, testicular cancer, mixed germ cell tumors; normally made by fetus (commonly elevated due to underestimation of gestational age) b-HCG: hydatidiform moles & choriocarcinomas CA-19-9: pancreatic adenocarcinoma CA-125: ovarian cancer CEA: nonspecific; colorectal, pancreatic Ca S-100: neural crest origin (melanomas, neural tumors, schwannomas), langerhans cell histiocytosis (tennis racket) TRAP: Tartrate-Resistant Acid Phosphatase; hairy cell leukemia (B-cell neoplasm) |
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Tumor nomenclature
Carcinoma versus Sarcoma Method of spread & exceptions |
C: implies epithelial origin
S: implies mesenchymal origin Carcinomas typically spread via lymphatics, while sarcomas spread via blood Notable exceptions: RCC (renal vein); HCC (hepatic vein); follicular carcinoma of thyroid, and choriocarcinoma |