Thin basement membrane disease pathophysiology: Difference between revisions
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{{Thin basement membrane disease}} | {{Thin basement membrane disease}} | ||
{{CMG}} | {{CMG}} | ||
{{AE}} {{MMT}} | |||
==Overview== | ==Overview== | ||
[[Thin basement membrane disease]] is usually caused by [[Heterozygous]] [[mutation]] in [[COL4A3]] and [[COL4A4]] [[gene]] in [[autosomal]] nonprogressive [[dominant]] pattern and [[heterozygous]] [[mutation]] in [[COL4A5]] [[gene]] in [[X-chromosome]] may cause [[Thin basement membrane disease]] in [[female.]]. [[Alport syndrome]], [[IgA nephropathy]] are among the most common to have association with [[Thin basement membrane disease]]. Gross [[pathology]] usually shows no distinctive features although [[Diffuse]] thinning of [[GBM]] in [[electron microscopy]], [[Erythrocytes]] in between [[renal tubules]] ad [[bowman's membrane]], Minimal [[glomerular]] change or [[Mesangial cell|mesangial]] expansion on [[light microscopy]] are seen on [[microscopic]] [[histopathological]] analysis. | |||
==Pathophysiology== | ==Pathophysiology== | ||
The | '''[[Physiology]]''' | ||
[[Glomerular]] [[Basement membrane|Basement membrane]]<nowiki/>e consists of [[laminin]], [[Type-IV collagen|Type 4 collagen]], [[heparan sulfate]] proteoglycan and [[nidogen]]. [[Type-IV collagen|Type 4 collagen]] is generally composed of Gly-X-Y [[amino acids]] rich in six alpha chains (alpha 1-6) that gives [[Type-IV collagen|type 4 collagen]] a [[trimeric]] shape. The nascent [[GBM]] is made up of [[alpha 1 and 2]] initially, then alpha 3-4 [[trimers]] are secreted after [[glomerular]] [[capillaries]] formation which becomes the major component of [[Type-IV collagen|type 4 collagen]] and giving the [[GBM]] its stability.<ref name="pmid22410250">{{cite journal |vauthors=Miner JH |title=The glomerular basement membrane |journal=Exp. Cell Res. |volume=318 |issue=9 |pages=973–8 |date=May 2012 |pmid=22410250 |pmc=3334451 |doi=10.1016/j.yexcr.2012.02.031 |url=}}</ref> | |||
'''[[Pathology]]''' | |||
[[Heterozygous]] [[mutation]] in [[COL4A3]] and [[COL4A4]] [[gene]] is responsible for causing [[autosomal]] [[dominant]] pattern of 40-50% of [[Thin basement membrane disease]] in which people have defective alpha 3, alpha 4 , alpha 5 chains. <ref name="pmid22410250">{{cite journal |vauthors=Miner JH |title=The glomerular basement membrane |journal=Exp. Cell Res. |volume=318 |issue=9 |pages=973–8 |date=May 2012 |pmid=22410250 |pmc=3334451 |doi=10.1016/j.yexcr.2012.02.031 |url=}}</ref> And [[heterozygous]] [[mutation]] in [[COL4A5]] [[gene]] in [[X-chromosome]] may cause [[Thin basement membrane disease]] in [[female.]]. | |||
'''[[Genetics]]''' | |||
[[Thin basement membrane disease]] is an [[inherited]] pattern [[disease]] affecting successive generations. It may be due to- | |||
*[[Autosomal dominant inheritance]] due to [[heterozygous]] [[mutation]] in [[COL4A3]] and [[COL4A4]] [[gene]] | |||
*[[Heterozygous]] [[mutation]] in [[COL4A5]] gene in [[X-chromosome]] causing [[Thin basement membrane disease|Thin basement membrane]] like disease in [[female]] | |||
*'<nowiki/>'''[[De novo]]'''' [[mutation]].<ref name="pmid15880327">{{cite journal |vauthors=Rana K, Wang YY, Buzza M, Tonna S, Zhang KW, Lin T, Sin L, Padavarat S, Savige J |title=The genetics of thin basement membrane nephropathy |journal=Semin. Nephrol. |volume=25 |issue=3 |pages=163–70 |date=May 2005 |pmid=15880327 |doi=10.1016/j.semnephrol.2005.01.008 |url=}}</ref> | |||
'''Associated condition''' | |||
Condition associated with [[Thin basement membrane disease]] include: | |||
*[[Alport syndrome]] | |||
**[[Alport syndrome]] is caused by [[homozygous]] or [[heterozygous]] [[mutation]] of both or either [[COL4A3]], [[COL4A4]] and [[COL4A5]] gene, thus 36% of cases of [[Thin basement membrane disease|TBMD]] with [[COL4A3]], [[COL4A4]] [[mutation]] are shown to be associated with [[Alport syndrome]].<ref name="pmid11318937">{{cite journal |vauthors=Buzza M, Wilson D, Savige J |title=Segregation of hematuria in thin basement membrane disease with haplotypes at the loci for Alport syndrome |journal=Kidney Int. |volume=59 |issue=5 |pages=1670–6 |date=May 2001 |pmid=11318937 |doi=10.1046/j.1523-1755.2001.0590051670.x |url=}}</ref> | |||
*[[IgA nephropathy]]. | |||
'''Gross pathology''' | |||
On gross [[pathology]], there is no distinctive features suggesting [[Thin basement membrane disease|TBMD.]] | |||
'''Microscopic pathology''' | |||
On [[microscopic]] [[histopathological]] analysis, the followings features are noted: | |||
*[[Erythrocytes]] in between [[renal tubules]] ad [[bowman's membrane]]<ref name="pmid2371004">{{cite journal |vauthors=Bailey RR |title=Familial haematuria due to thin basement membrane nephropathy |journal=N. Z. Med. J. |volume=103 |issue=893 |pages=312–3 |date=July 1990 |pmid=2371004 |doi= |url=}}</ref> | |||
*[[Diffuse]] thinning of [[GBM]] in [[electron microscopy]] in around 50% of [[population]] with [[Thin basement membrane disease|TBMD]].<ref name="pmid15880325">{{cite journal |vauthors=Foster K, Markowitz GS, D'Agati VD |title=Pathology of thin basement membrane nephropathy |journal=Semin. Nephrol. |volume=25 |issue=3 |pages=149–58 |date=May 2005 |pmid=15880325 |doi=10.1016/j.semnephrol.2005.01.006 |url=}}</ref> Occassionally, segmental thinning of [[GBM]] is present in [[Thin basement membrane disease|TBMD.]]<ref name="pmid17090197">{{cite journal |vauthors=Ivanyi B, Pap R, Ondrik Z |title=Thin basement membrane nephropathy: diffuse and segmental types |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=10 |pages=1533–7 |date=October 2006 |pmid=17090197 |doi=10.1043/1543-2165(2006)130[1533:TBMNDA]2.0.CO;2 |url=}}</ref> | |||
*Minimal [[glomerular]] change or [[Mesangial cell|mesangial]] expansion may be present on [[light microscopy]].<ref name="urlRedirecting">{{cite web |url=https://doi.org/10.1016/B978-1-4160-3966-2.00029-1 |title=Redirecting |format= |work= |accessdate=}}</ref> | |||
==References== | ==References== | ||
Latest revision as of 09:31, 21 December 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Marufa Marium, M.B.B.S[2]
Overview
Thin basement membrane disease is usually caused by Heterozygous mutation in COL4A3 and COL4A4 gene in autosomal nonprogressive dominant pattern and heterozygous mutation in COL4A5 gene in X-chromosome may cause Thin basement membrane disease in female.. Alport syndrome, IgA nephropathy are among the most common to have association with Thin basement membrane disease. Gross pathology usually shows no distinctive features although Diffuse thinning of GBM in electron microscopy, Erythrocytes in between renal tubules ad bowman's membrane, Minimal glomerular change or mesangial expansion on light microscopy are seen on microscopic histopathological analysis.
Pathophysiology
Glomerular Basement membranee consists of laminin, Type 4 collagen, heparan sulfate proteoglycan and nidogen. Type 4 collagen is generally composed of Gly-X-Y amino acids rich in six alpha chains (alpha 1-6) that gives type 4 collagen a trimeric shape. The nascent GBM is made up of alpha 1 and 2 initially, then alpha 3-4 trimers are secreted after glomerular capillaries formation which becomes the major component of type 4 collagen and giving the GBM its stability.[1]
Heterozygous mutation in COL4A3 and COL4A4 gene is responsible for causing autosomal dominant pattern of 40-50% of Thin basement membrane disease in which people have defective alpha 3, alpha 4 , alpha 5 chains. [1] And heterozygous mutation in COL4A5 gene in X-chromosome may cause Thin basement membrane disease in female..
Thin basement membrane disease is an inherited pattern disease affecting successive generations. It may be due to-
- Autosomal dominant inheritance due to heterozygous mutation in COL4A3 and COL4A4 gene
- Heterozygous mutation in COL4A5 gene in X-chromosome causing Thin basement membrane like disease in female
- 'De novo' mutation.[2]
Associated condition
Condition associated with Thin basement membrane disease include:
- Alport syndrome
- Alport syndrome is caused by homozygous or heterozygous mutation of both or either COL4A3, COL4A4 and COL4A5 gene, thus 36% of cases of TBMD with COL4A3, COL4A4 mutation are shown to be associated with Alport syndrome.[3]
- IgA nephropathy.
Gross pathology
On gross pathology, there is no distinctive features suggesting TBMD.
Microscopic pathology
On microscopic histopathological analysis, the followings features are noted:
- Erythrocytes in between renal tubules ad bowman's membrane[4]
- Diffuse thinning of GBM in electron microscopy in around 50% of population with TBMD.[5] Occassionally, segmental thinning of GBM is present in TBMD.[6]
- Minimal glomerular change or mesangial expansion may be present on light microscopy.[7]
References
- ↑ 1.0 1.1 Miner JH (May 2012). "The glomerular basement membrane". Exp. Cell Res. 318 (9): 973–8. doi:10.1016/j.yexcr.2012.02.031. PMC 3334451. PMID 22410250.
- ↑ Rana K, Wang YY, Buzza M, Tonna S, Zhang KW, Lin T, Sin L, Padavarat S, Savige J (May 2005). "The genetics of thin basement membrane nephropathy". Semin. Nephrol. 25 (3): 163–70. doi:10.1016/j.semnephrol.2005.01.008. PMID 15880327.
- ↑ Buzza M, Wilson D, Savige J (May 2001). "Segregation of hematuria in thin basement membrane disease with haplotypes at the loci for Alport syndrome". Kidney Int. 59 (5): 1670–6. doi:10.1046/j.1523-1755.2001.0590051670.x. PMID 11318937.
- ↑ Bailey RR (July 1990). "Familial haematuria due to thin basement membrane nephropathy". N. Z. Med. J. 103 (893): 312–3. PMID 2371004.
- ↑ Foster K, Markowitz GS, D'Agati VD (May 2005). "Pathology of thin basement membrane nephropathy". Semin. Nephrol. 25 (3): 149–58. doi:10.1016/j.semnephrol.2005.01.006. PMID 15880325.
- ↑ Ivanyi B, Pap R, Ondrik Z (October 2006). "Thin basement membrane nephropathy: diffuse and segmental types". Arch. Pathol. Lab. Med. 130 (10): 1533–7. doi:10.1043/1543-2165(2006)130[1533:TBMNDA]2.0.CO;2. PMID 17090197.
- ↑ "Redirecting".