Amyloidosis

Question 1

What does amyloid consist of?

Answer 1

Physical nature of amyloid
All types of amyloid consist of continuous, non-branching fibrils. Cross--pleated sheet conformation.

Chemical nature of amyloid
95% amyloid material consists of fibrils protein, 5% P component and other glycoproteins.

Question 2

What are the common forms of amyloid?

Answer 2

Common forms of amyloid:
AL (amyloid light chain) protein is made up of complete immunoglobulin light chains (mostly ), the amino terminal fragments of light chains, or both.

AA (amyloid-associated) type is derived from a unique non-Ig protein made by the liver. AA fibrils are derived by proteolysis of SAA (serum amyloid-associated) protein. It’s production increase in inflammatory state and its associated with chronic inflammation.
-amyloid protein (A) consists the core of cerebral plaque fond in Alzheimer disease. A is derived by the proteolysis of amyloid precursor protein.

Protein that deposit as amyloid

• Transthyretin (TTR) is a normal serum protein that binds and transport thyroxin and retinol. Mutant form causes its deposition.
• beta-2-microglobulin is a component of MHC I.
• Misfolded prion proteins can aggregate in ECM in CNS.
• Serum amyloid P protein contribute to amyloid deposition by stabilizing the fibrils and decreasing their clearance.

Question 3

What is primary amyloidosis?

Answer 3

Primary amyloidosis- when its associated with plasma cell disorder. It is systemic and usually AL type. It is caused by a clonal proliferation of plasma cells that synthesized an Ig that is likely to form amyloid due to its intrinsic physiochemical properties.
- Malignant plasma cells synthesize abnormal amount of single Ig (depends on it amino acid). The plasma cell often secret free, unpaired  and  light chains. These can be found in urine, serum and deposited in tissue (as amyloid).

Question 4

What is reactive systemic amyloidosis?

Answer 4

Reactive systemic amyloidosis- It’s systemic in distribution and are composed of AA protein. In this form of amyloidosis, SAA synthesis, by the liver cells, is stimulated by IL-6 & IL-1 that are produced during inflammation.

Question 5

Heredofamilial amyloidosis?

Answer 5

Heredofamilial amyloidosis – Most common is a condition called familial Mediterranean fever. It’s an autosomal recessive syndrome associated with excessive production of cytokine IL-1 in response to inflammatory stimuli.

Question 6

What is hemodialysis-associated amyloidosis?

Answer 6

Hemodialysis-associated amyloidosis – result of deposition of 2 microglobulin, which is presented in high concentration in the serum of person with renal disease.

Question 7

What is localized amyloidosis?

Answer 7

Localized amyloidosis – Deposit are limited to a certain organ. The deposition produces grossly nodular mass.

Question 8

What are the morphologies of amyloidosis?

Answer 8

Morphology
Histologically, the amyloid deposition is always extracellular and begin between cells, often adjacent to the base membrane. As the amyloid accumulates, its encroaches on the cell and destroy them.

Question 9

What are the symtoms of amyloidosis?

Answer 9

Symptoms
Depends on magnitude of deposition and organ affected. Include weakness, weight loss, light headedness and bleeding.

• Amyloidosis of the tongue may cause sufficient enlargement and inelasticity to hamper speech and swallowing.
• In some cases: AL amyloid binds and inactivate factor x, a critical coagulation factor, leading to a life-threatening bleeding disorder.