Nelson- Amyloidosis Flashcards
Define amyloidosis
group of disorders where amyloid is deposited in extracellular space of tissues and organs> tissue organ and dysfunction
What is the characteristic appearance of amyloid in tissue sections?
Pathological proteins w similar physical properties (4-6 fibrils wound around one another)
Linear non branching fibrils in cross beta pleated sheet configuration > characteristic staining
What special stain is used to view amyloidosis?
H&E- amorphous, eosinophillic, hylaline, extracelluar substance–> pressure atrophy of adjacent cells
Congo red- appears red
On polarization= red stained amyloid exhibits green birefringence
Is amyloidosis a single disease entity or a group of diseases?
Group of disorders that have amyloid deposited in places
How does amyloid injure adjacent cells?
Deposited amyloid–> tissue and organ dysfunciton
What are the 5 types of amyloid protein?
AL- amyloid light chain AA- amyloid associated AB- beta amyloid protein TTR- transthyretin B2- microglobluin
AL- pathological mechanism
monoclonal population of plasma cells>
produces free Ig light chain protein>
AL
AL- precursor proteins
complete Ig light chains (lamda L)
amino terminal fragments of L chains or both
AA- pathological mecahnism
Increased SAA production + enzyme defect>
incomplete SAA break down>
deposition
**SAA production increased in inflammatory conditions> chronic inflammation
AA- precursor proteins
Proetolysis of serum amyloid protein (SAA)
often associated w/ high density lipoprotein
AB- precursor proteins
Proetolysis of amyloid precursor protein
AB- pathological mechanism
Found in cerebral plaques and walls of cerebral vessels in Alzheimers disease
TTR- precursor protein
Mutated TTR
Normal serum protein that binds and transports thyroxine and retinol
TTR- pathological mechanism
Mutated TTR (Heritable neuropathic/cardiomyopathic amyloidosis) > amyloid deposition
Non-mutated TRR (senile systemic amyloidosis) > TRR deposition in heart of aged pts
B2 microglobulin- precursor protein
normal serum protein
B2 microglobluin- pathological mechanism
Cannot be filtered through dialysis membranes>
accumulates in long term dialysis
(hemodialysis associated amyloidosis)
What can cause localized amyloidosis?
prion diseases>
accumulation in CNS
What is the mechanism for amyloidosis?
abnormal protein folding into fibrils>
increased resistance to normal degradation>
accumulation of mysfolded protein
(classified by type of protein produced)
Define systemic amyloidosis
involving several organ systems
Define localized amyloidosis
involving a single organ (heart)
Define primary amyloidosis
associated w/ an immunocyte (plasma cell, B cell disorder)
Define secondary amyloidosis
complication of an underlying chronic inflammatory process
Define hereditary/familal amyloidosis
group of heterogenous heritable forms of amyloidosis w/ several distinctive patterns of organ involvement
Describe primary amyloidosis.
AL- most common type in the US
Monoclonal proliferation of plasma cells>
production of monoclonal IgL/Ig H chains (w/out H chain= bence jones protein)>
AL/AH>
systemic>
heart, kidney, periohperal nerve, GI tract
What type of light chain deposition is seen in pts w/ multiple myeloma?
Monoclonal free L chain>
deposition
Describe reactive systemic amyloidosis.
2nd most common type
Chronic inflammatory condition (RA), ct disorder, inflammatory bowel disorder>
serum AA>
AA amyloidosis (high density apolipoproteins)>
systemic>
kidney, liver, spleen
What is the most common type of amyloidosis in the developing world and why?
AA is most common b/c of chronic infectious disease
AA (reactive) is associated w/ what cancers?
REneal cell carcinoma
Hodgkin lymphoma
Describe hemodialysis associated amyloidosis.
Prolonged periods of dialysis to treat end stage renal disease> B2 microglobulin> Ab2m> deposition of B2 microglobulin> bone structures
Describe Heredofamilial amyloidosis (two types)
Mutated TTR (heritable/cardiomyopathic amyloidosis)> amyloid deposition
Non-mutated TTR (senile systemic amyloidosis)>
TTR deposition in heart of aged pts
Describe age related systemic amyloidosis
Cardiac amyloidosis d/t normal TTR
Normal TTR protein>
deposition in heart>
cardiomyopathy and arrhythmia
*elderly 70-80s
What is a hereditary type of amyloidosis commonly seen in african americans?
Mut in Ile22 indicates cardiac amyloidosis d/t mut TRR
mut allele commonly seen in African americans-> screen for this
Describe localized (organ specific) amyloidosis
Nodular deposition in lung, larynx, skin, urininary bladder, tongue, orbi
*limited to 1 organ/tissue
most common: amyloid plaques and amyloid laden cerebral vessels in AD
What precursor protein is associated w/ alzheimers and where is it distributed?
APP> AB
cerebral plaques
cerebral vessels
What organ systems are most commonly affected by systemic amyloidosis?
kidneys, heart , liver
What are some of the key clinical sxs associated w/ systemic amyloidosis?
waxy skin easy bruising enlarged muscles heart failure cardiac conduction abnormalities heptatomegaly renal dysfunciton peripheral/autnomic neuropathy impaired coagulation (factor X def)
How do you dx amyloidosis/
Gold standard: tissue biopsy w/ amyloid stainging
How do you dx suspected systemic disease?
fat pad aspiration (from abdomen) or rectal biopsy
How do you determine the type of ayloid present?
immunohistochemistry
liquid chromatography
mass spec
How do you treat amyloidosis?
AA
AL
Dialysis realted
herediatry forms w/ TTR
Varies w/ amt of amyloid produced
AA- target underlying infection/inflamm disorder
AL- underlying PC disorder
Dialysis related- alter mode of dialysis or renal transplant
herediatry forms w/ TTR- liver transplant
