Etiopathogenesis Of Amyloidosis

Describe etiopathogenesis
Or
Describe etiopathogenesis and classify amyloidosis.
Answer:

Etiopathogenesis Of Amyloidosis

Different mechanisms are involved in different types of amyloid. In general amyloidogenesis in vivo occurs in the following sequence:

A pool of amyloidogenic precursor protein is present in the circulation in different clinical settings and in response to stimuli, For Example. increased hepatic synthesis of AA or ATTR, increased synthesis of AL, etc.
Nidus for fibrillogenesis: Thereby an alteration in the microenvironment to stimulate the deposition of amyloid protein. This alteration involves changes and interactions between basement membrane proteins and amyloidogenic proteins.
Partial degradation or proteolysis: It occurs prior to the deposition of fibrillar protein which may occur in macrophages or reticuloendothelial cells, For Example. inAL, AA, etc. Exceptions to this generalization are seen in ATTR, Ab2M, and prognosis.
The role of non-fibrillar components such as AP, apoE, and GAGs in amyloidosis is unclear; probably they facilitate the aggregation of proteins and protein folding leading to fibril formation, substrate adhesion, and protection from degradation.

Etiopathogenesis of amyloidosis

Deposition of AL Amyloid

The stimulus for the production of AL amyloid is some disorder of immunoglobin synthesis, For Example. multiple myeloma, B cell lymphoma, and other plasma cell dyscrasias.
Excessive immunoglobulin production is in the form of monoclonal gammopathy, i.e. there is the production of either intact immunoglobulin, or λ light chain, or κ light chain, or rarely heavy chains. This takes place through monoclonal
the proliferation of plasma cells, B lymphocytes, or their precursors.
Partial degradation in the form of limited proteolysis of larger protein molecules occurs in macrophages which are anatomically closely associated with AL amyloid.
Non-fibrillar components like AP and GAGs play some role in the folding and aggregation of viral proteins.

Amyloidosis causes and mechanism

Deposition of AA Amyloid

AA amyloid is directly related to SAA levels. SAA is a high-density lipoprotein the levels of which are elevated in long-standing tissue destruction accompanied by chronic inflammation.
SAA is synthesized by the liver in response to cytokines, notably interleukin l and 6, from activated macrophages. However, SAA levels in isolation do not always lead to AA amyloid.
As in AL amyloid, partial degradation in the form of limited proteolysis takes place in reticuloendothelial cells.
In AA amyloid, a significant role is played by glycoprotein, amyloid enhancing factor (AEF). The composition of AEF is not known. It is elaborated in chronic inflammation, cancer, and familial Mediterranean fever. Possibly AEF acts as a nidus for the deposition of fibrils in AA amyloid.
As in AL amyloid, there is the role of the AP component and glycosaminoglycans in the final protein aggregation and to protect it from disaggregation again.

Reader Interactions