Pathology Flashcards
Apoptosis
Intrinsic: increased Bax, now Bcl2 and Cy2 release
Extrinsic
1) Fas ligand binding to CD95
2) Cytotoxic T cells releasing perforin and granzyme B
Apoptosis characteristic
Nuclear shrinkage (pyknosis)
Basophila,
Membrane blebbing
Nuclear fragmentation (karyorrhexis)
Necrosis
Coag: heart, liver, kidney
Liquefactive: brain, bacterial abscess, pleural effusion
Caseous: TB, systemic fungi
Fatty: peripancreatic fat
Fibrinoid: blood vessels
Gangrenous: dry or wet, common in GI or limbs
Cell injury reversible
low ATP synthesis
Cellular swelling (no ATP, impaired Na/K)
Nuclear chromatin clumping
Low glycogen
Fatty change
Ribosomal detachment (low protein synthesis)
Cell injury irreversible
Nuclear pyknosis, karyolysis, karyorrhexia Ca influx => caspase activation Plasma membrane damage Lysosomal rupture Mitochondrial permeability
Ischemia
Brain: ACA/MCA/PCA boundary areas
Heart: subendocaridum
Kidney: straight segment of proximal tube (medulla), thick ascending limb (medulla)
Liver: area around the central vein (zone III)
Colon: splenic flexure, rectum
Hypoxic ischemic encephalopathy affects myramidal cells of hippocampus and Purkinje cells.
Atrophy
Decreased hormone (uterus/vagina)
Decreased innervation (motor neuron damage)
Decreased blood flow
Decreased nutrients
High pressure (nephrolithiasis)
Occlusion of secretory ducts (cystic fibrosis)
Extravasation
Rolling: epithelial (E and P-selection), leuk(Sialyl Lewis)
Tight binding: epithelial (ICAM-1=CD54), leuk (LFA1)
Diaspedesis: epithelial AND leuk (PECAM-1)
Migration: bacterial products (c5a, IL8, LTB4, Kallikrekin)
Free radial injury
Via radiation, metabolism of drug, redox rxn, NO, transition medals, oxidative burst.
Eliminated by enzymes (catalase, superoxide, dismutase, glutathion peroxidase) spontanous decay, antioxidants.
Pathologides: retinopathy of prematurity, bronchopulmonary dysplasia, CCl4 (liver necrosis and fatty change), acetaminophen (fulminant hepatitis), iron overload, reperfusion after anoxia.
Wound healing
Inflammatory: plt, neutrophil, MP
Proliferative (2-3 days): fibroblasts, myofibroblasts, endothelial cells, keratinoctes, MP
Remodeling (1wk after): fibroblasts, Type III replaced by Type I.
Granulomatous diseases
TB, fungal, syphilis, M leprae, Bartonella henselae, sarcoidosis, Crohns, Wegeners, Churg-Strauss, Berylliosis, silicosis
ESR
Elevated: Infection, inflammation (temporal arteritis), cancer, pregnancy, SLE
Reduced: sickle (atered shaped), polycythemia (too many), CHF(unknown)
*In general, when aggregated, precipitate faster
Iron poisoing
Causes membrane peroxidation
Acute: gastric bleeding
Chronic: metabolic acidosis, scarring leading to GI obstruction.
Amyloidosis
Abnormal aggregation of proteins or their fragments into beta pleated sheet structures, leading to cell damage and apoptosis. Affected tissue has waxy appearance.
AL: deposition of Ig LIGHT chain, with MM
AA: Amyloid A from chronic diseases such as RA, IBD, spondyloarthropathy, chronic infection.
Dialysis: b2-microglobulin in ESRD and long-term dialysis, often presenting with CARPAL TUNNEL and other joint issues.
Heritable: examples, ATTR neurologic/cardiac due to transthyretin (TTR or prealbumin) gene mutation
Age related (senile): normal WT TTR in myocardium and other sites. slower progression of cardiac dysfunction than AL amyloidosis
Organ-specific: Amyloid deposition localized to a single organ. Most important form is amyloidosis in Alzheimer’s disease due to deposition of amyloid beta protein cleaved from APP.
Neoplasma
Hyperplasia: increase in number
Dysplasia: abnormal proliferation with loss of size, shape, and orientation
Carcinoma in situ: not invaded basement membrane, high nuclear/cytoplasmic ratio and clumped chromatin. Neoplastic cells encompass entire thickness
Invasive: express collagenases and hydrolases to metastasize.
