Flashcards in Path Pre-Unifieds Deck (138)
Amyloid light chain. Usually associated with lambda B cell diseases. Primary systemic amyloidosis.
Amyloid associated non-ig protein from SAA. SAA is high in chronic inflammatory diseases, produced in liver. Chronic inflammation --> macrophage activation --> IL-1 and 6 --> liver cells --> SAA protein-- >limited proteolysis, AA protein buildup.
Immunocyte dyscrasias with Amyloidosis
Deposition of AL or their fragments in extracellular spaces throughout body. Abnormal clones of B cells ie multiple myeloma. Excess Ig and light chains only (Bence Jones proteins).
Reactive systemic amyloidosis
Deposition of AA protein in EC space of most organs and systems. Used to be called secondary amyloidosis bc often associated with chronic inflamm processes. Usually secondary to autoimmune disease, neoplasms (hodgkins), and chronic skin infections. TBC, chronic osteomyelitis, bronchiectasis.
Extreme iron overload, genetic. Cardiac failure, hepatic cirrhosis, and diabetes. Bronze like appearance "bronze diabetes". Also increased risk of malignant tumours of liver (hepatocellular carcinoma)
Familial Systemic Amyloidosis
Buildup of AA or transthyretin (Mediterranean fever, neuropathies)
Familial Mediterranean fever
AR disorder of PMN function, AA deposits occur
Familial amyloidotic neuropathies
AD , many mutations in amyloidogenic proteins. Most common subtype is transthyretin mutation
Senile localized amyloidosis of Heart
Less severe, don't really understand. Associated with transthyretin, often asymptomatic and discovered at autopsy.
Urate crystal precipitation. (1) Activation of complement, neutrophil chemotax, phagocytosis, lysis of neutrophils, release of more crystals, lysosomal enzymes, tissue injury inflamm. (2) phagocytosis by macrophages, release of LTB4, PGI, free radicals - neutrophil chemotax, activation of inflammasome, release of IL-1B, secretion of chemokines and other cytokines, protases, tissue injury and inflamm.
Cell Injury: Lysosomes
Usually due to drugs and antibiotics. Can cause autophagy by activation of lysosomal enzymes with enzymatic digestion of cell components --> necrosis. Can cause incomplete degradation of phagocytosed material (lysosomes lose ability to degrade if lose enzymes).
Cell injury: mitochondria
Usually due to any agent that affects oxidative phosphorylation ie hypoxia, hypoglycemia. Lack of O2 as the final electron acceptor
Cell injury mechanisms leading to necrosis
Hypoxia, ischemia, decreased ATP --> necrosis. Increase in ROS from injurious stimuli, damage to lipids proteins and nucleic acids --> necrosis. Inflammation, releases toxic molecules, necrosis (or apoptosis)
Cell injury mechanisms leading to apoptosis
Mutations, cell stress, infections => Accumulation of mis-folded proteins in ER => apoptosis.
Radiation, other insults => DNA damage => apoptosis
Inflammation from infections, immuno disorders => toxic molecules => apoptosis (or necrosis)
Reversible Ischaemic injury
Impaired aerobic resp., decreased ATP, anaerobic glycolysis, glycogen depletion, lactic acidosis and nuclear chromatin clumping.
ATP deficiency --> energy loss --> cell membrane integrity --> failure of NA pump --> cel swelling and calcium influx --> Lactate accumulation (also leads to cell swelling) --> detachment of ribosomes --> blebs, myelin figures (cell membrane) --> mitochondrial swelling.
IRREV ischaemic injury
Severe vacuolization of mitochondria, damage of plasma membranes, swelling of lysosomes and MASSIVE Calcium influx, marked intracellular acidosis, ruptured lysosomal membrane, cell digestion and death. Inability of mitochondria to recover. Calcium influx denatures proteins and causes cell coagulation.
When is injury irreversible?
Mitochondria unable to recover after re-oxygeniation --> lloss of phospholipids --> damage to cytoskeleton --> O2 free radicals and lipid break products (ROS), influx of calcium fater re-ox with protein denaturation (coagulation of cells).
Free radical injury
Most affect cell membranes. Most common are activatd oxygen radicals (aging, chemical, infections, inflamm etc). Free radicals affect cell membranes by lipid peroxidation, and affect nucleic acids with mutations. Protective mechanisms = catalase and glutathione.
Chemical injury (direct or indirect)
Direct: mercury binds to protiens and cell membranes
indirect: by metabolic activation ie CCl4 --> Ccl3 in ER (irreversible fatty change)
Accumulation of lipid in cells (ER) because of lack of lipoproteins necessary for TAGs to leave the cell --> fatty liver.
Viral injury (cytopathic or cytolytic or oncogenic effect)
Cytopathic - rapid replication within cell, immune response, inflammation, and cell lysis
Often cell specific (receptors)
Also effects on cell skeleton--> multinucleation, inclusino bodies etc.
Physiological usually. Cell shrinks. Eventual fragmentation of nucleus and cell--> apoptotic body --> phagocytized --> residual (acidophilic) body. NO INFLAMMATION.
Most common type. Ischaemic, coagulation of cells, loss of nuclei, denatured proteins. Acidophilic mass on H&E. Wedge shaped infarcts.
Hydrolytic enzymes. Brain, bacterial infections.
Can occur anywhere there is fat. Dystrophic calcification, metastatic calcification. Release of lipases fro pancreas or inflammatory cells, FFAs plus calcium --> soaps. Chalky cheesy nodules deposit.
TB. Combination of coagulative and liquefactive. Cheesy-milky. Eosinophilic (ie acidophilic, pink).
affects limbs. Ischemia and infection. Dry or wet - wet once liquefactive (bacteria), infection of dry one.
Intracellular accumulation. Accumulation of Immunoglobulins in RER of plasma cells --> eosinophilic.
Mechanisms of intracellular accumulations
Abnormal metabolism (fatty liver, defect in protein folding, transport, lack of enzyme (lysosomal storage diseases, endogenous materials), ingestion of indigestible materials (exogenous, ie carbon pigment accumulation)
Simple columnar to stratified squamous. Squamous metaplasia. Due to multiple kids, HPV, etc. Pap smear to test.