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==Pathophysiology==
==Pathophysiology==
'''Physiology'''
'''[[Physiology]]'''


Glomerular Basement membrane 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.<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>
[[Glomerular]] [[Basement membrane|Basement membran]]<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'''
'''[[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 mamebrane disease in female.   
[[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'''
'''[[Genetics]]'''


Thin basement membrane disease is an inherited pattern disease affecting successive generations. It may be due to-  
[[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  
*[[Autosomal dominant inheritance]] due to [[heterozygous]] [[mutation]] in [[COL4A3]] and [[COL4A4]] [[gene]]
*''''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>  
*[[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'''
'''Associated condition'''


Condition associated with Thin basement membrane disease include:
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 TBMN 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>  
*[[Alport syndrome]]
*IgA nephropathy.
**[[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]].<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'''
'''Gross pathology'''


On gross pathology, there is no distinctive features suggesting TBMD.
On gross [[pathology]], there is no distinctive features suggesting [[TBMD.]]


'''Microscopic pathology'''
'''Microscopic pathology'''


On microscopic histopathological analysis, the followings features are noted:
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>
*[[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 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 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>
*[[Diffuse]] thinning of [[GBM]] in [[electron microscopy]] in around 50% of [[population]] with [[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 [[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 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>
*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>




Revision as of 07:58, 20 October 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Pathophysiology

Physiology

Glomerular Basement membrane 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]

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. [1] 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-

Associated condition

Condition associated with Thin basement membrane disease include:

Gross pathology

On gross pathology, there is no distinctive features suggesting TBMD.

Microscopic pathology

On microscopic histopathological analysis, the followings features are noted:


References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ Bailey RR (July 1990). "Familial haematuria due to thin basement membrane nephropathy". N. Z. Med. J. 103 (893): 312–3. PMID 2371004.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ "Redirecting".

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