Path - Inflammation (Amyloidosis & Lipofuscin)

Question 1

What is amyloidosis? What 2 major effects does it have?

Answer 1

Abnormal aggregation of proteins (or their fragments) into Beta-pleated sheet structures => damage and apoptosis

Question 2

What are 6 common types of amyloidosis?

Answer 2

(1) AL (primary) (2) AA (secondary) (3) Dialysis-related (4) Heritable (5) Age-related (senile) systemic (6) Organ-specific

Question 3

What is the amyloid in AL amyloidosis? Is this primary or secondary amyloidosis?

Answer 3

Due to deposition of proteins from Ig Light chains; AL (primary); Think: “aL = ig Light chains”

Question 4

What is the amyloid in AA amyloidosis? Is this primary or secondary amyloidosis?

Answer 4

Fibrils composed of serum Amyloid A; AA (secondary); Think: “AA = serum Amyloid A”

Question 5

What are 2 conditions in which AL amyloidosis can occur?

Answer 5

Can occur as a plasma cell disorder or associated with multiple myeloma

Question 6

To what extent does AL (primary) amyloidosis usually affect the body? Give 5 examples.

Answer 6

Often affects multiple organ systems, including (1) renal (nephrotic syndrome), (2) cardiac (restrictive cardiomyopathy, arrhythmia), (3) hematologic (easy bruising), (4) GI (hepatomegaly), and (5) neurologic (neuropathy)

Question 7

In what type of conditions is AA (secondary) amyloidosis seen? Give 4 examples of such conditions.

Answer 7

Seen with chronic conditions, such as rheumatoid arthritis, IBD, spondyloarthropathy, protracted infection

Question 8

How does AA (secondary) amyloidosis compare/contrast to AL (primary) amyloidosis in terms of its effects/extent?

Answer 8

Often multisystem like AL amyloidosis

Question 9

What is the amyloid in dialysis-related amyloidosis? What are 2 patient populations/settings in which this may occur?

Answer 9

Fibrils composed of Beta2-microglobulin in patients with ESRD and/or on long-term dialysis

Question 10

How may dialysis-related amyloidosis present?

Answer 10

May present as carpal tunnel syndrome

Question 11

Briefly describe heritable amyloidosis (in terms of how it is defined).

Answer 11

Heterogenous group of disorders

Question 12

What is an example of heritable amyloidosis? What causes this?

Answer 12

Example is ATTR neurologic/cardiac amyloidosis due to transthyretin (TTR or prealbumin) gene mutation

Question 13

What amyloid causes age-related (senile) systemic amyloidosis, and where?

Answer 13

Due to deposition of normal (wildtype) TTR in myocardium and other sites

Question 14

How does age-related (senile) systemic amyloidosis compare to AL amyloidosis in terms of progression of cardiac dysfunction?

Answer 14

Slower progression of cardiac dysfunction relative to AL amyloidosis

Question 15

What is the definition of organ-specific amyloidosis?

Answer 15

Amyloid deposition localized to a single organ

Question 16

What disease is the most important form of organ-specific amyloidosis, and what is the amyloid?

Answer 16

Most important form is amyloidosis in Alzheimer disease due to deposition of amyloid-Beta protein cleaved from amyloid precursor protein (APP).

Question 17

What kind of amyloidosis is Islet amyloid peptide (IAPP)? In what condition is it commonly seen, and what causes it?

Answer 17

Organ-specific; Islet amyloid polypeptide (IAPP) is commonly seen in diabetes mellitus type 2 and is caused by deposition of amylin in pancreatic islets

Question 18

What stain shows amyloidosis? What special visualization technique can be used, and how does amyloidosis appear in this case?

Answer 18

Congo red stain shows amyloid deposit; Congo red stain shows apple green birefringence under polarized light

Question 19

What is lipofuscin? With what process is it associated?

Answer 19

A yellow-brown “wear and tear” pigment associated with normal aging

Question 20

What mechanism(s) form(s) lipofuscin?

Answer 20

Formed by oxidation and polymerization of autophagocytosed organellar membranes

Question 21

In autopsy of what patient population is lipofuscin seen, and where in the body?

Answer 21

Autopsy of elderly person will reveal deposits in heart, liver, kidney, eye, and other organs