What do thyroid tumor cells in an amyloid background indicate?
medullary carcinoma of the thyroid
This is systemic deposition of AL amyloid derived from the Ig light chain; assoc with plasma cell dyscrasias.
1a amyloidosis
What is amylin?
an amyloid that is a byproduct of insulin that can deposit in the islets of the pancreas
What is senile cardiac amyloidosis?
non-mutated serum transthyretin deposits in the heart present in 25% of individuals >80yo usually asymptomatic
What is 1a amyloidosis?
systemic deposition of AL amyloid derived from the Ig light chain; assoc with plasma cell dyscrasias
What is systemic deposition of AA amyloid derived from SAA called?
2a amyloidosis
What are non-mutated serum transthyretin deposits in the heart called?
senile cardiac amyloidosis
dx? mutated serum transthyretin deposits in the heart leads to restrictive cardiomyopathy 5% of African Americans are carriers
familial amyloid cardiomyopathy
Name the localized amyloidoses.
- familial amyloid cardiomyopathy 2. senile cardiac amyloidosis 3. DM associated 4. Alzheimers 5. dialysis-associated amyloidosis 6. medullary carcinoma of the thyroid
What is dialysis-associated amyloidosis?
beta-2-microglobulin deposits in joints dialysis pts
What is medullary carcinoma of the thyroid?
a thyroid tumor derived from C cells, leading to overproduction of calcitonin and then amyloid deposition in the thyroid
Dx? beta-2-microglobulin deposits in joints
dialysis-associated amyloidosis
How does amyloid look under the microscope?
congo red staining with apple green birefringence
What is the usual configuration of amyloid-damaged tissue?
Beta-pleated sheets
How can amyloidosis occur in Alzheimers disease?
beta-amyloid precursor protein on chromosome 21 deposits into the brain as ABeta forms amyloid plaques
Systemic amyloidosis is divided into ____ and ____ types.
1a; 2a
What are non-mutated serum transthyretin deposits in the heart called?
senile cardiac amyloidosis
How can amyloidosis occur in DM?
type 2 DM: too much insulin = insulin byproduct produced (amylin) amylin deposits into islets of the pancreas
What are the features of Familial Mediterranean Fever?
dysfunction of the neutrophils causing activation w/o infection auto recessive inheritance in persons of Mediterranean origin fever; serosal surfaces inflamed; tongue enlargement, hepatosplenomegaly, malabsorption
How is amyloidosis definitively diagnosed?
a tissue biopsy (usu a fat pad- abdominal or rectal)
What is the usual configuration of amyloid-damaged tissue?
Beta-pleated sheets
Name the localized amyloidoses.
- familial amyloid cardiomyopathy 2. senile cardiac amyloidosis 3. DM associated 4. Alzheimers 5. dialysis-associated amyloidosis
What is restrictive cardiomyopathy?
stiffened heart can’t dilate as well or pump properly, leading to HF
How can amyloidosis occur in Alzheimers disease?
beta-amyloid precursor protein on chromosome 21 forms ABeta amyloid forms amyloid plaques in the brain
What is 2a amyloidosis?
systemic deposition of AA amyloid derived from SAA
Where does amyloid most commonly deposit? What does this cause?
the kidney; nephrotic syndrome
What is an amyloid?
a misfolded protein that deposits into the extracellular space
What is SAA?
an acute phase reactant increased in inflammation, malignancy, and Familial Mediterranean fever
What kind of amyloidosis category does senile cardiac amyloidosis fall into?
localized amyloidosis
What is familial amyloid cardiomyopathy?
mutated serum transthyretin deposits in the heart leads to restrictive cardiomyopathy 5% of African Americans are carriers
What is nephrotic syndrome?
a large loss of protein (>3g in 24 hours) in the urine
How are the affected organs treated in amyloidosis?
no tx- they have to be transplanted
Where does amyloid tend to deposit?
around BVs
What is the 2nd most common protein in the blood?
serum transthyretin
What is AA amyloid?
an amyloid derived from SAA
What is the difference btw familial amyloid cardiomyopathy and senile cardiac amyloidosis ?
familial = mutated serum transthyretin senile = non-mutated serum transthyretin
Why does dialysis-assoc amyloidosis occur?
Dialysis pts have increased amounts if Beta-2-microglobulin in the blood bc it isn’t filtered out properly- it then accumulates in joints
What are the features of Familial Mediterranean Fever?
dysfunction of the neutrophils causing activation w/o infection auto recessive inheritance in persons of Mediterranean origin fever; serosal surfaces affected
Dx? dysfunction of the neutrophils causing activation w/o infection auto recessive inheritance in persons of Mediterranean origin fever; serosal surfaces affected
Familial Mediterranean Fever
What is the link btw Alzheimers and Down Syndrome?
the beta-amyloid precursor protein is on chromosome 21 and DS = trisomy 21 early Alzheimers seen in DS individuals
What are the features of Familial Mediterranean Fever?
dysfunction of the neutrophils causing activation w/o infection auto recessive inheritance in persons of Mediterranean origin fever; serosal surfaces inflamed
What is the amyloid that is a byproduct of insulin that can deposit in the islets of the pancreas?
amylin
What is a misfolded protein that deposits into the extracellular space called?
an amyloid
How is medullary carcinoma of the thyroid definitively diagnosed?
fine needle aspiration of the thyroid
What is AL amyloid derived from?
Ig light chain
Where does amyloid most commonly deposit? What does this cause?
the kidney; nephrotic syndrome
What is restrictive cardiomyopathy?
stiffened heart can’t dilate as well or pump properly, leading to HF
Systemic amyloidosis is divided into ____ and ____ types.
1a; 2a
What is the difference btw familial amyloid cardiomyopathy and senile cardiac amyloidosis ?
familial = mutated serum transthyretin senile = non-mutated serum transthyretin
2a amyloidosis can result from a _____, like autoimmune disease (SLE, RA, Crohn’s, etc), ______, or _____.
chronic inflammatory state; malignancy; Familial Mediterranean fever
Why are amyloids bad?
they damage tissues
What can happen to the heart in amyloidosis?
restrictive cardiomyopathy arrhythmia
Where does amyloid tend to deposit?
around BVs
Where does amyloid most commonly deposit? What does this cause?
the kidney; nephrotic syndrome
What are non-mutated serum transthyretin deposits in the heart called?
senile cardiac amyloidosis
Amyloid deposition can be _____ or _____.
systemic; localized
What is the difference btw familial amyloid cardiomyopathy and senile cardiac amyloidosis ?
familial = mutated serum transthyretin senile = non-mutated serum transthyretin
How are the affected organs treated in amyloidosis?
no tx- they have to be transplanted
What kind of amyloidosis is dialysis-associated?
localized
2a amyloidosis can result from a _____, like autoimmune disease (SLE, RA, Crohn’s, etc), or _____.
chronic inflammatory state; malignancy
What is AL amyloid derived from?
Ig light chain
What is the link btw Alzheimers and Down Syndrome?
the beta-amyloid precursor protein is on chromosome 21 and DS = trisomy 21 early onset Alzheimers seen in DS individuals
What is Beta-2-microglobulin?
a supportive protein for MHCI expression
What is serum transthyretin?
the 2nd most common protein in the blood
What is dialysis-associated amyloidosis?
beta-2-microglobulin deposits in joints
What is AA amyloid?
an amyloid derived from SAA
How is amyloidosis definitively diagnosed?
a tissue biopsy (usu a fat pad- abdominal or rectal)
What is a large loss of protein (>3g in 24 hours) in the urine called?
nephrotic syndrome
What is medullary carcinoma of the thyroid?
a thyroid tumor derived from C cells, leading to overproduction of calcitonin, leading to amyloid deposition in the thyroid
Why does dialysis-assoc amyloidosis occur?
Dialysis pts have increased amounts if Beta-2-microglobulin in the blood bc it isn’t filtered out properly- it then accumulates in joints
Where is the beta-amyloid precursor protein gene located?
on chromosome 21
What can happen to the heart in amyloidosis?
restrictive cardiomyopathy arrhythmia
What is localized amyloidosis?
amyloid deposition localized to a single organ or tissue
What are non-mutated serum transthyretin deposits in the heart called?
senile cardiac amyloidosis
