Amyloidosis pathophysiology: Difference between revisions
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==== Secondary Amyloidosis (AA) ==== | ==== Secondary Amyloidosis (AA) ==== | ||
* Secondary amyloidosis is associated with chronic [[inflammation]] (such as tuberculosis or rheumatoid arthritis).<ref name=" | * Secondary amyloidosis is associated with chronic [[inflammation]] (such as tuberculosis or rheumatoid arthritis).<ref name="pmid116772762">{{cite journal |vauthors=Khan MF, Falk RH |title=Amyloidosis |journal=Postgrad Med J |volume=77 |issue=913 |pages=686–93 |date=November 2001 |pmid=11677276 |pmc=1742163 |doi= |url=}}</ref> | ||
* Secondary or reactive amyloidosis (AA) is approximately 45% of all systemic amyloidosis.<ref name="pmid119640392">{{cite journal |vauthors=Röcken C, Shakespeare A |title=Pathology, diagnosis and pathogenesis of AA amyloidosis |journal=Virchows Arch. |volume=440 |issue=2 |pages=111–122 |date=February 2002 |pmid=11964039 |doi=10.1007/s00428-001-0582-9 |url=}}</ref> | * Secondary or reactive amyloidosis (AA) is approximately 45% of all systemic amyloidosis.<ref name="pmid119640392">{{cite journal |vauthors=Röcken C, Shakespeare A |title=Pathology, diagnosis and pathogenesis of AA amyloidosis |journal=Virchows Arch. |volume=440 |issue=2 |pages=111–122 |date=February 2002 |pmid=11964039 |doi=10.1007/s00428-001-0582-9 |url=}}</ref> | ||
* [[Pathogenesis]] of secondary or reactive amyloidosis is multifactorial that include: | * [[Pathogenesis]] of secondary or reactive amyloidosis is multifactorial that include: | ||
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==== Hereditary Amyloidosis ==== | ==== Hereditary Amyloidosis ==== | ||
* Hereditary (or familial) amyloidosis are autosomal dominant diseases that inherited variant proteins cause the production and deposition of amyloid fibrils.<ref name=" | * Hereditary (or familial) amyloidosis are autosomal dominant diseases that inherited variant proteins cause the production and deposition of amyloid fibrils.<ref name="pmid116772762">{{cite journal |vauthors=Khan MF, Falk RH |title=Amyloidosis |journal=Postgrad Med J |volume=77 |issue=913 |pages=686–93 |date=November 2001 |pmid=11677276 |pmc=1742163 |doi= |url=}}</ref> | ||
* 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> | * 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|Transthyretin (TTR)]] (most common inherited mutation) | ** [[Transthyretin|Transthyretin (TTR)]] (most common inherited mutation) | ||
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===Gross Pathology=== | ===Gross Pathology=== | ||
===Microscopic Pathology=== | ===Microscopic Pathology=== | ||
In microscopy pathology of amyloidosis, [[amyloid]] is detectable as:<ref name="pmid119640392">{{cite journal |vauthors=Röcken C, Shakespeare A |title=Pathology, diagnosis and pathogenesis of AA amyloidosis |journal=Virchows Arch. |volume=440 |issue=2 |pages=111–122 |date=February 2002 |pmid=11964039 |doi=10.1007/s00428-001-0582-9 |url=}} | In microscopy pathology of amyloidosis, [[amyloid]] is detectable as:<ref name="pmid119640392">{{cite journal |vauthors=Röcken C, Shakespeare A |title=Pathology, diagnosis and pathogenesis of AA amyloidosis |journal=Virchows Arch. |volume=440 |issue=2 |pages=111–122 |date=February 2002 |pmid=11964039 |doi=10.1007/s00428-001-0582-9 |url=}}<ref name="pmid116772762">{{cite journal |vauthors=Khan MF, Falk RH |title=Amyloidosis |journal=Postgrad Med J |volume=77 |issue=913 |pages=686–93 |date=November 2001 |pmid=11677276 |pmc=1742163 |doi= |url=}}</ref> | ||
* Typical green [[birefringence]] under [[Polarization|polarized]] light after [[Congo red]] staining (appears in red under normal light) | * Typical green [[birefringence]] under [[Polarization|polarized]] light after [[Congo red]] staining (appears in red under normal light) | ||
* Linear non-branching [[Fibril|fibrils]] (indefinite length with an approximately same diameter) | * Linear non-branching [[Fibril|fibrils]] (indefinite length with an approximately same diameter) | ||
Revision as of 14:18, 6 June 2018
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Amyloidosis Microchapters |
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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]
- Amyloid deposition can disrupt tissue structure of involved organ and consequently leads to organ failure.[4]
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 (AL)
- Primary amyloidosis (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 or tertiary structure of a monoclonal light chain results in abnormal folding of the light chain that abnormally form amyloid fibrils.[5]
- This type of amyloidosis most frequently involve the kidney (usually proteinuria with the nephrotic syndrome) and the heart.[6]
Secondary Amyloidosis (AA)
- Secondary amyloidosis is associated with chronic inflammation (such as tuberculosis or rheumatoid arthritis).[6]
- Secondary or reactive amyloidosis (AA) is approximately 45% of all systemic amyloidosis.[7]
- 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 (or familial) amyloidosis are autosomal dominant diseases that inherited variant proteins cause the production and deposition of amyloid fibrils.[6]
- Hereditary amyloidosis are due to amyloidogenic mutations and subsequently deposition of amyloids, include:[8]
- Transthyretin (TTR) (most common inherited mutation)
- Fibrinogen
- Apolipoprotein A1
- Apolipoprotein A2
- Lysozyme
- Gelsolin genes
Organ-specific Amyloidosis
Gross Pathology
Microscopic Pathology
In microscopy pathology of amyloidosis, amyloid is detectable as:
- 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
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.
- ↑ Jerzykowska S, Cymerys M, Gil LA, Balcerzak A, Pupek-Musialik D, Komarnicki MA (2014). "Primary systemic amyloidosis as a real diagnostic challenge - case study". Cent Eur J Immunol. 39 (1): 61–6. doi:10.5114/ceji.2014.42126. PMC 4439975. PMID 26155101.
- ↑ Desport E, Bridoux F, Sirac C, Delbes S, Bender S, Fernandez B, Quellard N, Lacombe C, Goujon JM, Lavergne D, Abraham J, Touchard G, Fermand JP, Jaccard A (August 2012). "Al amyloidosis". Orphanet J Rare Dis. 7: 54. doi:10.1186/1750-1172-7-54. PMC 3495844. PMID 22909024.
- ↑ 6.0 6.1 6.2 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.
- ↑ 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.