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Pathobio Exam 1
Set 4: Cellular Alterations 5
78
Pathology
Graduate
10/07/2011

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Cards

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
T, I, & C
Term
def

troponins
Definition
components of an intracellular protein complex integral to striated muscle contraction
Term
Function

troponins
Definition
regulate the calcium-mediated interaction b/w actin & myosin
Term
What can cause elevated serum levels of cardiac troponins?
Definition
cellular damage due to necrosis => increased permeability & leakage
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
ALT & AST
Term
Function

Transaminases
Definition
catalyze removal & transfer of an amino group from an amino acid to an α-keto acid
Term
What do transaminases use as a co factor?
Definition
Vit B6
Term
What are transaminases important for in the liver?
Definition
energy production & nitrogen excretion
Term
What causes elevated serum ALT & AST?
Definition
hepatic membrane damage due to necrosis => increased permeability & leakage
Term
Are ASTs or ALTs more specific for liver damage?

Why?
Definition
ALTs since AST is found in other tissues
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
5
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
LD-1 thru LD-5
Term
Which LD isoenzyme has 4 M chains?
Definition
LD-5
Term
Which LD isoenzyme has 4 H chains?
Definition
LD-1
Term
Where are LD-1 seen?
Definition
myocardium & RBCs
Term
Where are LD-2 seen?
Definition
WBCs
Term
Where are LD-3 seen?
Definition
lungs
Term
Where are LD-4 seen?
Definition
kidneys, pancreas, & placenta
Term
Where are LD-5 seen?
Definition
skeletal muscle & liver
Term
*Which LD isoenzyme predominates in the serum?
Definition
LD-2
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
Where is amylase found?
Definition
pancreas & saliva (salivary α-amylase)
Term
Where is lipase found?
Definition
pancreas
Term
Function

Amylase
Definition
catalyze hydrolysis of α(1-4) glycoside bonds in starch to form simple sugars
Term
Function

Lipase
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
Term
Is elevated lipase or amylase more sensitive for acute pancreatisis?
Definition
lipase
Term
def

Apoptosis
Definition
highly regulated pattern of cell death occuring via cascade
Term
Can apoptosis coexist with necrosis?
Definition
yes
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
endonuclease
Term
What 3 biochemical alterations occur in apoptotic cells?
Definition
1) proteolysis
2) DNA fragmentation
3) cell membrane modification
Term
def

proteolysis
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
def

Telomere
Definition
short, repetitive nucleotide sequences located at the ends of chromosomes which help protect replication of intervening DNA
Term
def

Telomerase
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
def

cellular senescence
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
Dystrophic & Metasatic
Term
def

*Dystrophic
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
def

Metastatic
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
def

psammoma bodies
Definition
circular concretions with concentric layering
Term
Does dystrophic or metastatic calcification cause tissue dysfunction?
Definition
dystrophic
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