Term
| What are the 4 serum lab markers for necrosis? |
|
Definition
1) troponins
2) transaminases
3) lactate dehydrogenase
4) amylase & lipase |
|
|
Term
| What are the 3 subunits of troponins? |
|
Definition
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Term
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Definition
| components of an intracellular protein complex integral to striated muscle contraction |
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Term
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Definition
| regulate the calcium-mediated interaction b/w actin & myosin |
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Term
| What can cause elevated serum levels of cardiac troponins? |
|
Definition
| cellular damage due to necrosis => increased permeability & leakage |
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|
Term
| What are the 3 clinical uses of testing for serum troponins? |
|
Definition
1) sensitive & specific for early indication myocardial necrosis
2) persistant elevated levels => myocardial injury (up to 2 weeks)
3) prognostic |
|
|
Term
| What are the 2 transaminases tested for in the serum? |
|
Definition
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Term
|
Definition
| catalyze removal & transfer of an amino group from an amino acid to an α-keto acid |
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Term
| What do transaminases use as a co factor? |
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Definition
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Term
| What are transaminases important for in the liver? |
|
Definition
| energy production & nitrogen excretion |
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|
Term
| What causes elevated serum ALT & AST? |
|
Definition
| hepatic membrane damage due to necrosis => increased permeability & leakage |
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|
Term
Are ASTs or ALTs more specific for liver damage?
Why? |
|
Definition
| ALTs since AST is found in other tissues |
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|
Term
| Are AST & ALT used for prognostic purposes? |
|
Definition
| No, since levels of elevation don't correlate with extent of liver damage or prognosis |
|
|
Term
| Where are lactate dehydrogenases (LDs) found? |
|
Definition
| widely distributed in various tissue |
|
|
Term
| How many tetrameric isoenzymes does LD have? |
|
Definition
|
|
Term
| *What are the 5 tetrameric isoenzymes of LD composed of? |
|
Definition
| various combination of H & M chains |
|
|
Term
| What are the 5 LD tetrameric isoenzymes? |
|
Definition
|
|
Term
| Which LD isoenzyme has 4 M chains? |
|
Definition
|
|
Term
| Which LD isoenzyme has 4 H chains? |
|
Definition
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Term
|
Definition
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Term
|
Definition
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Term
|
Definition
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Term
|
Definition
| kidneys, pancreas, & placenta |
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Term
|
Definition
|
|
Term
| *Which LD isoenzyme predominates in the serum? |
|
Definition
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|
Term
Function
Lactate Dehydrogenase |
|
Definition
| catalyze conversion of pyruvate to lactate & vice versa |
|
|
Term
| What causes elevated serum levels of LD? |
|
Definition
| membrane damage in necrosis => increased permeability & leakage |
|
|
Term
| What are the 2 clinical uses of increased serum LD? |
|
Definition
nonspecific indication of necrosis
if LD-1>LD-2, indicated MI |
|
|
Term
|
Definition
| pancreas & saliva (salivary α-amylase) |
|
|
Term
|
Definition
|
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Term
|
Definition
| catalyze hydrolysis of α(1-4) glycoside bonds in starch to form simple sugars |
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Term
|
Definition
| catalyze hydrolysis of triglycerides into monoglycerides & free fatty acids |
|
|
Term
| What causes increased serum amylase & lipase? |
|
Definition
| pancreatic duct obstruction/acinar cell injury => inappropriate pancreatic enzyme release & activation => pancreatic lysis and increased serum amylase & lipase |
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|
Term
| Is elevated lipase or amylase more sensitive for acute pancreatisis? |
|
Definition
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|
Term
|
Definition
| highly regulated pattern of cell death occuring via cascade |
|
|
Term
| Can apoptosis coexist with necrosis? |
|
Definition
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|
Term
| How is apoptosis used physiologically? |
|
Definition
| mechanism for removal of cells which become unecessary or deleterious to the individual |
|
|
Term
| What are 4 examples of physiological use of apoptosis? |
|
Definition
1) embryologic development
2) loss of hormonal/GF stimulation
3) cytotoxic T-cell response
4) deletion of lymphocytes that recognize self-Ag |
|
|
Term
| What are 3 examples of when might apoptosis be used pathologically? |
|
Definition
1) viral inf.
2) irreparable damage to DNA (radiation)
3) accumulation of lg. quantities of defective folded proteins |
|
|
Term
| What are the 4 key mechanisms to apoptosis initiation? |
|
Definition
1) extrinsic, death receptor-mediated
2) intrinsic, mitochondrial
3) p53
4) perforin/granzyme |
|
|
Term
| What is the extrinsic, death receptor-mediated pathway of apoptosis? |
|
Definition
| binding of Fas ligan to Fas receptor => cross-linking Fas receptors => binding cytoplasmic domains of receptors to FADD (Fas-associated death domain) adapter protein => activation of caspase cascade |
|
|
Term
| What is the intrinsic, mitochondrial pathway of apoptosis? |
|
Definition
| decreased hormonal/GF stimulation => replacement of anti-apoptotic proteins in mitochondrial membrane => increased mitochondrial permability => release of pro-apoptotic molecules to cytosol => activation of caspase cascade |
|
|
Term
| What is the p53 pathway of apoptosis? |
|
Definition
detection of DNA damage => increased levels & activation of p53 => cell-cycle arrest & attempted DNA repair
if unsuccessful repair => p53-induced transcriptional activation of pro-apoptotic genes => caspase activation |
|
|
Term
| What is the perforin/granzyme pathway of apoptosis? |
|
Definition
| cytotoxic T-cell (CTL) recognition of foreign Ag presented by MHC I => CTL secretion of perforin & subsequent release of granzyme B => activation of caspase cascade |
|
|
Term
| How is apoptosis executed? |
|
Definition
| caspase cascade (proteases activated by cleavage of inactive pro-enzyme) |
|
|
Term
| What degrades first in apoptosis? |
|
Definition
| cytoskeletal & nuclear matrix proteins |
|
|
Term
| What nust be activated prior to DNA cleavage in apoptosis? |
|
Definition
|
|
Term
| What 3 biochemical alterations occur in apoptotic cells? |
|
Definition
1) proteolysis
2) DNA fragmentation
3) cell membrane modification |
|
|
Term
|
Definition
| breakdown of nuclear structure & cytoskeleton |
|
|
Term
| What causes the DNA ladder pattern in electrophoresis (DNA fragmentation) in apoptosis? |
|
Definition
| DNase activation => enzymatic cleavage of nuclear DNA |
|
|
Term
| How are apoptotic cells removed without an inflammatory response? |
|
Definition
| expression of unique cell surface molecules & secretion of substances => enhanced macrophage recruitment, recognition, opsonization & phagocytosis |
|
|
Term
| Why are apoptotic cells frequently inapparent? |
|
Definition
1) targeting of single cells
2) rapidity
3) absence of inflammation |
|
|
Term
| What do apoptotic cells look like microscopically? |
|
Definition
| rounded, condense, hypereosinophilic cell with peripherally compacted nuclear chromatin (eventual nuclear/cytoplasmic fragmentation) => formation of dense apoptotic bodies |
|
|
Term
| What apoptotic disorders are there? |
|
Definition
1) decreased apoptosis (s.a autoimmune)
2) increased apoptosis (s.a. neurodegenerative) |
|
|
Term
| What influences cellular aging? |
|
Definition
| genetic & exogenous factors |
|
|
Term
|
Definition
| short, repetitive nucleotide sequences located at the ends of chromosomes which help protect replication of intervening DNA |
|
|
Term
|
Definition
| enzyme that helps restore telomeres are incomplete nucleotide duplication during cell divion |
|
|
Term
| Where are telomerases active? |
|
Definition
| Germ cells & lesser extent in stem cells (none in somatic cells) |
|
|
Term
| What helps germ cells retain cellular replicative capacity? |
|
Definition
| telomerase activity to maintain chromosomal telomeres |
|
|
Term
| What happens in somatic cells without telomerase activity? |
|
Definition
| gradual loss of telomere length => eventual damage to ends of intervening DNA => cellular senescence |
|
|
Term
|
Definition
| inabilit for further cell division |
|
|
Term
| What happens as somatic cells lose the length of their telomeres? |
|
Definition
| Gradual loss of functional abilities |
|
|
Term
| What affects cumulative nonlethal cell injury? |
|
Definition
| amount of cellular damage, accumulation of abnormal metabolic byproducts, & cellular reparative ability |
|
|
Term
| What 3 parts of the cell can see cumulative nonlethal cellular injury? |
|
Definition
1) membranes
2) chromosomes
3) organelles |
|
|
Term
| What are the 2 major types of calcification? |
|
Definition
|
|
Term
|
Definition
| normal serum levels & metabolism of calcium. It's site specific & disrupts function. |
|
|
Term
| What causes dystrophic calcification? |
|
Definition
| tissue injury/death => increased membrane permeability & formation of extracellular vesicles => influx of Ca2+ & blinding of Ca2+ to the vesicle membrane => addition of phosphate (PO4) groups => development & propagation of intra- & extra- cellular calcium phosphate crystals |
|
|
Term
| What are 3 examples of dystrophic calcification? |
|
Definition
1) atherosclerotic plaques
2) pulmonary nodule secondary to histoplasmosis
3) long-standing, congenital bicuspid aortic valve |
|
|
Term
|
Definition
| calcium deposits systemically, but doesn't disrupt function (initially) |
|
|
Term
| What causes metastatic calcification? |
|
Definition
| increased serum levels of Ca2+ => systemic deposition of Ca2+ salts |
|
|
Term
| What are 3 examples of metastatic calcification? |
|
Definition
1) increased PTH => bone resorption
2) lytic skeletal disorders => done destruction
3) inceased Vit D activity |
|
|
Term
| Where does dystrophic calcification occur? |
|
Definition
| focal sites of tissue damage & necrosis |
|
|
Term
| Where does metastatic calcification occur? |
|
Definition
| normal organ with relatively alkaline interstitium |
|
|
Term
| What does calcification look like grossly? |
|
Definition
| hard, white foci (if sufficient quantity) |
|
|
Term
| What does calcification look like microscopicly? |
|
Definition
| basophilic particulate matter |
|
|
Term
| What unique variants can be seen microscopicly in dystropic calcification? |
|
Definition
| psammoma bodies & ectopic bone |
|
|
Term
|
Definition
| circular concretions with concentric layering |
|
|
Term
| Does dystrophic or metastatic calcification cause tissue dysfunction? |
|
Definition
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