Extracellular Accumulations Flashcards
Hyaline Substances
variety of EC proteinaceous accumulations have hyaline appearance in histology:
- protein casts in renal tubules
- serum/plasma in blood vessels
- plasma protein in vessel walls
- collagen fibers in some scars or collagen fibers encrusted with proteins from degranulated eosinophils
- thickened basement membranes
- hyaline membranes of diffuse alveolar damage in acute respiratory distress syndrom
- fibrin thrombi in DIC
- amyloid
Amyloidosis + Mechanisms
amyloidosis = disorders w/ common pathogenesis (protein misfolding) + generic morphologic appearance (fibrillar polypeptide chains rich in cross B sheets)
mechanisms include:
1) propagation of misfolded proteins that serve as template for self-replication
2) accumulation of misfolded precursor proteins d/t failure in degradation
3) genetic mutations that promote misfolding of precursor proteins
4) protein overproduction bc of abnormality or proliferation in sythesizing cells
5) loss of chaperoning mol. or other essential components of protein assembly process
Amyloid
if visible macroscopically = appears as yellow, waxy, coalescing nodular or amorphous deposits
iodine used as gross technique to stain amyloid
at light microscopic level = homogenous to indistinctly fibrillary + pale eosinophillic
with congo red stain = more orange-red hue (congophillia)
ultrastructurally = EC bundles of non-branching filaments
has characteristic apple-green birefringence in polarized light
- amyloid is anisotropic
AL amyloid
consisits of Ig light chains derived from dyscrasic/neoplastic plasma cells -> considered primary
can be systemic but can be limited to stroma
retains congophillia + apple-green birefringence after pretx with potassium permanganate
horses -> nasal amyloidosis
- conjunctiva + skin can also be affected
AA amyloid
consists of amyloid A protein produced mainly by hepatocytes
assoc. w/ chronic inflammation -> considered secondary
fibrils deposited in various tissues
- particular renal glomeruli, liver space of disse + splenic white pulp
hereditary or familial forms
sensitive to potassium permanganate -> loses congophillia + birefringence after pretx
shar-pei + abyssinians = deposits most abundant in renal medullary interstitium instead
Systemic Amyloidosis
more likely to be life threatening -> depends on organs involved + volume of amyloid deposits
diffuse + severe renal glomerular amyloidosis results in protein-losing nephropathy
Localized Amylodoisis
severity of dz depends more on biochemical nature of amyloid fibrils
-precursor oligomers rather than fibrils thought to be injurious agent
cats + human = deposited in pancreatic islets from islet amyloid polypeptide (IAPP) secreted by beta cells
- can be associated with insulin resistance (Type II) DM
accumulation of beta amylooid in cerebral cortex in aged dogs with CCD + human’s with alzheimers
Fibrinoid Change
result of leakage of plasma proteins into wall of BVs
**
observed in septic or immune-mediated vasculitis**
injury to endothelial cells, basement membrane or smooth muscle cells of tunica media can activate acute phase inflammatory response leading to circumferential deposition of plasma proteins in BVs wall
these proteins, esp. fibrin, are intensely eosinophillic + can be accompanied by leukocytic infiltration
Collagen (Fibrosis)
excess in fibrous collagen, mainly Type I collagen fibers, in interstitium
necrosis that destroys epithelial basement membranes + necrosis of mesenchymal tissues tend to induce proliferation of fibroblasts
in many injured tissues, especially beneath ulders or in wound healing, fibrosis is accompanied by endothelial proliferation with formation of granulation tissue
in liver, stellate cells are source of collagen in fibrosis
- macrophages direct fibrosis by releasing cytokines + growth factors
Fatty Infiltration
increase in # +/or vol. of adipocytes in interstitium of organ/tissue
increases in myocardiul interstitium = obesity, certain cardiomyopathies, skeletal myopathies
adipocytes also accumulate in atrophied tissues
Gout
dosition of sodium urate crystals (or urates) in tissue
- occurs in primates, birds, reptiles (not in domestics)
tophi may be visible grossly = pathognomonic
urate crystals acicular (needle-shaped) + negatively birefringent
birds + reptiles affected by 2 forms:
1) articular type (rare)
2) visceral type = affects visceral serosae -> gross appearance is diagnostic
- seen sporadically as result of vit. A deficiency, high protein diets + renal injury
- renal form = deposits in renal tubules + ureters
humans = urate crystals deposited in articular + periarticular tissues
elicit inflammatory response characterized by presence of neutrophils, macrophages + aggregates of urate crystals = tophi
Pseudogout
deposits of calcium pyrophosphate crystals
reported rarely in dogs
unknown pathogenesis
grossly, chalky white deposits of crystalline material in joints
Cholesterol
crystals dissolved out during histo processing -> leaves acicular clefts
form at sites of hemorrhage or necrosis + elicit granulomatous inflammation
present in atheromas + hypothyroid dogs
cholesteatomas = choroid plexus of lateral or 4th ventricles in old horses
- friable + pale + yellow nodules
- often an incidental finding
