Amyloidosis pathophysiology: Difference between revisions
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====Primary Amyloidosis==== | ====Primary Amyloidosis==== | ||
* | *Systemic light chain (AL) amyloidosis is the most common type: in which the amyloidogenic protein is a monoclonal light chain secreted by an underlying clonal plasma cell (or rarely B lymphoid) dyscrasia | ||
==== Secondary Amyloidosis ==== | ==== Secondary Amyloidosis ==== | ||
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** [[Lipid metabolism]] | ** [[Lipid metabolism]] | ||
** [[Protease|Proteases]] | ** [[Protease|Proteases]] | ||
==== Hereditary Amyloidosis ==== | |||
* Hereditary amyloidosis are due to amyloidogenic [[Mutation|mutations]] and subsequently deposition of [[Amyloid|amyloids]], include:<ref name="pmid24497558">{{cite journal |vauthors=Mahmood S, Palladini G, Sanchorawala V, Wechalekar A |title=Update on treatment of light chain amyloidosis |journal=Haematologica |volume=99 |issue=2 |pages=209–21 |date=February 2014 |pmid=24497558 |pmc=3912950 |doi=10.3324/haematol.2013.087619 |url=}}</ref> | |||
** Transthyretin (TTR) | |||
** Fibrinogen | |||
** Apolipoprotein A1 | |||
** Apolipoprotein A2 | |||
** Lysozyme | |||
** Gelsolin genes | |||
=== Organ-specific Amyloidosis === | === Organ-specific Amyloidosis === | ||
Revision as of 19:52, 8 May 2018
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Amyloidosis Microchapters |
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Diagnosis |
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Amyloidosis pathophysiology On the Web |
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Risk calculators and risk factors for Amyloidosis pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2]
Overview
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.[1][2]
- These abnormal amyloids derived from misfolding and aggregation of normally soluble proteins.[3]
- Approximately 27 amyloidogenic proteins that are associated with known human disease have been identified. The mutual feature of these proteins is their tendency to form β-pleated sheets that arranged in an antiparallel pattern. These sheets form rigid, non-branching fibrils that are proteolysis resistant. These sheets eventually cause mechanical disruption and local oxidative stress in affected organs.
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.[2][3]
Primary Amyloidosis
- Systemic light chain (AL) amyloidosis is the most common type: in which the amyloidogenic protein is a monoclonal light chain secreted by an underlying clonal plasma cell (or rarely B lymphoid) dyscrasia
Secondary Amyloidosis
- Secondary or reactive amyloidosis (AA) is approximately 45% of all systemic amyloidosis.[4]
- Pathogenesis of secondary or reactive 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
Hereditary Amyloidosis
- Hereditary amyloidosis are due to amyloidogenic mutations and subsequently deposition of amyloids, include:[5]
- Transthyretin (TTR)
- Fibrinogen
- Apolipoprotein A1
- Apolipoprotein A2
- Lysozyme
- Gelsolin genes
Organ-specific Amyloidosis
Gross Pathology
Microscopic Pathology
In microscopy pathology of amyloidosis, amyloid is detectable as:[4]
- Typical green birefringence under polarized light after Congo red staining
- 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
Other Diseases Associated with the Amyloid Protein
References
- ↑ Gillmore JD, Hawkins PN (October 2013). "Pathophysiology and treatment of systemic amyloidosis". Nat Rev Nephrol. 9 (10): 574–86. doi:10.1038/nrneph.2013.171. PMID 23979488.
- ↑ 2.0 2.1 Baker KR, Rice L (2012). "The amyloidoses: clinical features, diagnosis and treatment". Methodist Debakey Cardiovasc J. 8 (3): 3–7. PMC 3487569. PMID 23227278.
- ↑ 3.0 3.1 Pepys MB (2006). "Amyloidosis". Annu. Rev. Med. 57: 223–41. doi:10.1146/annurev.med.57.121304.131243. PMID 16409147.
- ↑ 4.0 4.1 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.
- ↑ Mahmood S, Palladini G, Sanchorawala V, Wechalekar A (February 2014). "Update on treatment of light chain amyloidosis". Haematologica. 99 (2): 209–21. doi:10.3324/haematol.2013.087619. PMC 3912950. PMID 24497558.