Amyloidosis

Question 1

primary amyloidosis

Answer 1

• MC amyloidosis
• amyloid light chain (AL)
• fibrillary protein = kappa or lambda light chains
• seen in plasma cell disorders (multiple myeloma, B cell lymphomas, etc)
• light chains are made by plasma cells –> tumor plasma cells –> excess light chains –> amyloidosis)
• amyloid deposits EXTRACELLULARLY!!!

Question 2

secondary amyloidosis

Answer 2

• aka reactive systemic amyloidosis (see in chronic inflammation) highest risk = untreated infection i.e. osteomyelitis
• amyloid associated amyloid (AA)
• fibrillary protein = serum amyloid A (SAA) = acute phase reactant produced by liver that’s elevated with ongoing chronic inflammation and neoplasia
• seen in RA (MCC in US), SLE, TB, bronchiectasis, osteomyelitis, Chrons, cancer

Question 3

familiar mediterranean fever

Answer 3

• amyloid associated amyloid (AA)
• fibrillary protein = serum amyloid A (SAA)
• AR
• recurrent inflammation, fever, neutrophil dysfunction

Question 4

hemodialysis associated amyloidosis

Answer 4

• Aβ2M amyloid
• fibrillary protein composed of β2- micro globulin
• may cause carpal tunnel syndrome (accumulates in median nerve)
• may accumulate in joints –> joint disease
• renal failure –> YEARS of dialysis

Question 5

senile cerebral amyloidosis

Answer 5

• alzheimers
• Aβ type amyloid with fibrillary protein composed of β-amyloid precursor protein (βAPP)
• found in alzheimer plaques and cerebral vessels
• gene for βAPP is on Ch 21 –> assoc with Downs

Question 6

senile cardiac/systemic amyloidosis

Answer 6

• ATTR type amyloid with fibrillary protein composed of transthyretin
• ATRR = transporter of thyroxine as well as retinal (Vit A) or retinol
• seen in men >70y
• may cause heart failure (restrictive/infiltrative cardiomyopathy)
• 4% of AA have transthyretin (TTR) V1221 mutation with 1% being homozygous –> risk for cardiac disease

Question 7

endocrine type amyloidosis

Answer 7

• seen in medullary carcinoma of thyroid (S 100+) –> produces procalcitonin –> amyloid deposits around tumor cells (only tumor in neck surrounded by amyloid)
• also seen in adult-onset diabetes (amylin) and pancreatic islet cell tumors (amylin)

Question 8

Systemic amyloidosis clinical features

Answer 8

• poor prognosis
• deposits EXTRACELLULARLY
• Kidney = MC involved organ –> nephrotic syndrome (proteinuria) and/or progressive renal failure
• cardiac (see between cardiac myocytes) –> restrictive cardiomyopathy, low voltage EKG, arrhythmias, CHF
• hepatosplenomegaly
• GI involvement –> malabsorption
• macroglossia (tongue enlargement; esp in AL type)
• best location to diagnose: abdominal fat pad (also tongue, rectal mucosa, gingiva)
• stains congo red and apple green birefringence