Amylodosis Flashcards
amyloid
pathological proteinaceous substance deposited in extracellular space in various tissues and organs of the body
what is an amyloid
amorphous
eosinophils
hyaline
how does amyloid damage?
with progressive accumulation it encroaches on and produces pressure atrophy of adjacent cells. it itself is not toxic
amyloidosis
should not be considered a signle disease–group of diseases having in common deposition of similar appearing proteins
amyloid protein is made up of
continuous, nonbranching fibrils in a cross-B-pleated sheet conformation (responsible for distinctive congo red staining) -95%
remaining 5%- P component and other glycoproteins
5 types of amyloidosis
primary amy secondary amy familial amy senile systemic amy dialysis amy
primary amyloidosis
K or gamma light chain/AL type
–multiple myeloma
but most cases do not have neoplasms
secondary amyloidosis
protein A (major component of amyloid fibril)
- -derived frm acute phase protein during chronic inflammation
- -serum amyloid A (precursor) is elevated with rheumatoid arthritis and Crohn’s disease
3 types of familial amyloidosis
neuropathic
cardiopathic
nephropathic
neuropathic familial amylodosis
portgual, sweden, japan, and other countries
- transthyretin mutant (prealbumin)
- ->peripheral neuropathy; sub of methionine for valine at residue 30
cardiomyopathy familial amylodosis
denmark and appalachia in US
-transthyretin mutant (prealbumin)
renal familial amylodosis
mediterranean fever
issue with neutrophils–> acute infammation because of this malfunction
mutation of fibrinogen a chain (leu 554 or Glu 526), or mutations of fibronogen a chain (protein a)
“autoinflammatory”-high IL1
senile systemic amylodosis
senile cardiac
transthryetin (TTR) normal (prealbumin)
ASYMPTOMATIC
dialysis amyloidosis
B2 microglobulin deposition
unknown carcinogen stimulus
monoclonal b lymphocyte proliferation–>plasma cells-
sol precursor misfolded protein: immunoglobulin light chain–> limited proteolysis–>AL protein
chronic inflammation stimulus
MO activation–>IL1 and IL6–>liver cells
sol. misfolded precursor preotein: Saa protein–>limited proteolysis–>AA protein
lichen amyloidosis
nodular amyloid deposits in skin
congo red makes amyloid appear
granny apple smith green
ATTR protein
what is made from normal ttr
mutation–>mutant ttr–>aggregation–>ATTR rotein
proteins of amyloid
AL-amyloid light chain AA-amyloid-associated AB amyloid Mutant Transthyretin (TTR) B2 microglobulin Prions
AA protein derived from
unique non-ig protein synthesized in liver
AB amyloid
produced from B amyloid precursor protein found in cerebral lesions of alzheimer disease
amyloid proteins fall in two categories
normal proteins that have inherent tendency to fold improperly, associate and form fibrils
mutant proteins that are prone to misfolding and subsequent aggregation
primary vs secondary amyloidosis
primary: associated with immunocyte disorder
secondary: complication of an underlying chronic inflammatory or tissue-destructive process
what is primary amyloidosis associated with?
plasma cell dyscrasia
most common organ of deposition
kidney- nephrotic syndrome (proteinuria)
type II diabetes
deposition of amylin in islets of pancreas
