Amyloid/TSE Flashcards
What is Amyloid?
Class of insoluble abnormal protein deposits
T/F: Amyloid is located both extracellularly and intracellularly?
True
Why does amyloid stain with iodine like starch?
Amyloid contains some carbohydrate components such as GAG and P-component
Amyloidosis
disease condition
Microscopically, what stain can be used to ultimately determine the presence of amyloid?
congo red stain - the appearance of green birefringence by using cross polarized light ultimately concludes amyloid presence
Systemic vs Localized
Systemic - involves more than one organ
Define Amyloid Fibrils
polymerized repetitive homologous peptide subunits
Amyloid Secondary structure?
B pleated sheet
Why does amyloid accumulate in tissues?
Due to its insolubility - this results in disruption of normal structures and impaired function
T/F: Amyloid oligomers and/or fibrils do not induce the cell stress response such as apoptosis?
False! Amyloid may be cytotoxic and thus induce the cell stress response
Briefly describe the 3 pathogenic types of amyloidosis.
- increased precursor protein production
- mutation to precursor protein (increased ability to form B pleated sheets)
- abnormal processing of precursor protein (Alzheimer’s disease)
What is the most serious systemic form of amyloidosis in mammals and birds?
secondary AA or secondary amyloid associated
- causes renal and hepatic failure
How does AA (secondary or reactive) amyloidosis occur?
IL-1 causes the liver to increase SAA (serum amyloid associated), macrophages degrade this 104 aa residue into a 76 aa fragment which leads to amyloid (AA?)
Canine amyloidosis is typically systemic or localized?
Systemic AA
Clinical signs in canine amyloidosis are typically?
renal failure - related to the glomerulus with marked proteinuria
The familial form of AA amyloidosis in ____________ dogs develops secondary to _____________?
Shar Pei dogs, Shar Pei Fever
T/F AA amyloid sequence in Shar Pei dogs is not the same as other breeds, and thus is the link to the genetic cause?
False - AA amyloid sequence IS the same as other breeds and thus IS NOT the genetic cause – HAS2 gene mutation is linked to this condition
Pulmonary vascular amyloid is a very common systemic form in canines. This is typically found in young/old dogs?
Old - over 10 years old
Pulmonary vascular amyloid is derived from what protein?
Apolipoprotein A1
T/F canine pulmonary vascular amyloid typically has clinical manifestations?
False - no clinical manifestations but rarely may see pulmonary hemorrhages
Beta protein derived cerebral amyloid is common in what canine breed?
Beagles
What is the neuropathology of beta-protein derived cerebral amyloid?
senile plaques (amyloid and cerebral vascular amyloidosis associated with cognitive dysfunction
Beta protein derived cerebral amyloid is similar pathologically and clinically to what human disease?
Alzheimer’s disease
Systemic AA amyloidosis is uncommon among felines except for? Name a few breeds!
Abyssinian, Siamese, & Oriental - develop a familial form
T/F Renal amyloidosis is typically seen with feline systemic AA amyloidosis?
False, hepatic amyloidosis is typically seen - sometimes renal
T/F Renal failure and rupture may occur in cats affected with systemic AA amyloidosis?
False! Hepatic failure and rupture may occur!
A mutation in what gene appears to increase amyloidogenicity in feline amyloidosis?
SAA gene (serum amyloid A)
A localized form of this organs functional unit is typically seen in feline amyloidosis?
Islet amyloidosis - nearly all type 2 diabetic cats have partial replacement of their islets with amyloid derived from islet amyloid polypeptide (IAPP)
Long standing insulin resistance (obesity) leads to an increased production of what pancreatic B cell hormone?
IAPP
What is the amyloid forming protein in feline islet amyloidosis? Why does it occur?
IAPP - this B cell protein is co-secreted with insulin and production is increased in obese cats who are insulin sensitive. Small IAPP amyloid oligomers are most cytotoxic and may also disrupt cell membranes
T/F Bovine systemic AA typically involves renal (proteinuria) and/or GI (severe diarrhea)?
True!! also associated with foot abscesses and necrotizing pododermatitis (i.e.. chronic inflammation/infection)
Systemic AA forms in equine amyloidosis usually involves ___________ and ___________?
liver and GI
Localized forms (AL - light chain origin) of equine amyloidosis occurs as a nodular _____________ form or a multinodular _____________ from leading to difficult breathing?
skin, nasopharyngeal
