Amyloidosis Pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Amyloid is an abnormal insoluble extracellular protein that deposits in the different tissues and causes organic dysfunction and a wide variety of clinical syndromes. In systemic amyloidosis, amyloid gradually accumulate and amyloid deposition is widespread in the viscera, blood vessel walls, and in the different connective tissues. Primary (AL) amyloidosis) is the most common type of amyloidosis. It results from aggregation and deposition of monoclonal immunoglobulin (Ig) light chains that usually produced by plasma cell clones. Secondary amyloidosis is associated with chronic inflammation (such as tuberculosis or rheumatoid arthritis). Hereditary (or familial) amyloidosis are autosomal dominant diseases that inherited variant proteins cause the production and deposition of amyloid fibrils. Some neurodegenerative disorders such as Parkinson's disease, Alzheimer, and Huntington's disease may occur in localised amyloidosis. On microscopic pathology, typical green birefringence under polarized light after Congo red staining (appears in red under normal light).
Pathophysiology
- Amyloid is an abnormal insoluble extracellular protein that deposits in the different tissues and causes organic dysfunction and a wide variety of clinical syndromes.
- These abnormal amyloids derived from misfolding and aggregation of normally soluble proteins.
- Amyloid deposition can disrupt tissue structure of involved organ and consequently leads to organ failure.
Systemic Amyloidosis
- In systemic amyloidosis, amyloid gradually accumulate and amyloid deposition is widespread in the viscera, blood vessel walls, and in the different connective tissues.[1][2]
Primary Amyloidosis (AL)
- Primary (AL) amyloidosis) is the most common type of amyloidosis. It results from aggregation and deposition of monoclonal immunoglobulin (Ig) light chains that usually produced by plasma cell clones.
- Change in the secondary structure or tertiary structure of a monoclonal light chain results in abnormal folding of the light chain that abnormally form amyloid fibrils.
- This type of amyloidosis most frequently involve the kidney (usually proteinuria with the nephrotic syndrome) and the heart.
- In primary (AL) amyloidosis survival rate depends on:
- Type of organ involvement (amyloid heart disease is the main prognostic factor)
- The severity of different organs involvement
- Haematological response to treatment
- The median survival of patients with AL amyloidosis is aproximately 3.8 years.
For more information about primary amyloidosis click here.
Secondary Amyloidosis (AA)
- Secondary amyloidosis is associated with chronic inflammation (such as tuberculosis or rheumatoid arthritis).[3]
- Secondary or reactive amyloidosis (AA) is approximately 45% of all systemic amyloidosis.
- Pathogenesis of secondary amyloidosis is multifactorial that include:
- Primary structure of the precursor protein
- Acute phase response
- Nonfibril proteins (amyloid P component, apo E, GAGs, proteoglycans and basement membrane proteins)
- Receptors
- Lipid metabolism
- Proteases
For more information about secondary amyloidosis click here.
Hereditary Amyloidosis
- Hereditary (or familial) amyloidosis are autosomal dominant diseases that inherited variant proteins cause the production and deposition of amyloid fibrils.[3]
- Hereditary amyloidosis are due to amyloidogenic mutations and subsequently deposition of amyloids, include:
Organ-specific Amyloidosis
- In this type of amyloidoses, amyloid deposition occurs only in the origin organ or tissue of precursor protein.
- Some neurodegenerative disorders such as Parkinson's disease, Alzheimer, and Huntington's disease may occur in localised amyloidosis.
- Localised amyloidoses can accure due to deposition of intracellular and/or extracellular amyloid.
- Huntington's disease: intracellular protein deposition
- Parkinson's disease: intracellular protein deposition
- Alzheimer's disease: intracellular (Tau protein fibrils) and extracellular (amyloid β fibrils) deposition
Microscopic Pathology
In microscopy pathology of amyloidosis, amyloid is detectable as:[4][3]
- Typical green birefringence under polarized light after Congo red staining (appears in red under normal light)
- Linear non-branching fibrils (indefinite length with an approximately same diameter)
- Distinct X-ray diffraction pattern consistent with Pauling's model of a cross-beta fibril
References
- ↑ Baker KR, Rice L (2012). "The amyloidoses: clinical features, diagnosis and treatment". Methodist Debakey Cardiovasc J. 8 (3): 3–7. PMC 3487569. PMID 23227278.
- ↑ Pepys MB (2006). "Amyloidosis". Annu. Rev. Med. 57: 223–41. doi:10.1146/annurev.med.57.121304.131243. PMID 16409147.
- ↑ 3.0 3.1 3.2 Khan MF, Falk RH (November 2001). "Amyloidosis". Postgrad Med J. 77 (913): 686–93. PMC 1742163. PMID 11677276.
- ↑ Röcken C, Shakespeare A (February 2002). "Pathology, diagnosis and pathogenesis of AA amyloidosis". Virchows Arch. 440 (2): 111–122. doi:10.1007/s00428-001-0582-9. PMID 11964039.