Bartter syndrome pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
==Pathophysiology== | ==Pathophysiology== | ||
*The thick ascending limb of the loop of Henle is not permeable to water and reabsorbs a large proportion of the filtered sodium chloride as shown in figure, which leads to interstitial hypertonicity that powers the countercurrent exchange and urinary concentration mechanisms. In case of impairment of this function, a major loss of water and sodium occurs, as seen with loop diuretics.<ref name="pmid21503667">{{cite journal| author=Seyberth HW, Schlingmann KP| title=Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects. | journal=Pediatr Nephrol | year= 2011 | volume= 26 | issue= 10 | pages= 1789-802 | pmid=21503667 | doi=10.1007/s00467-011-1871-4 | pmc=3163795 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21503667 }} </ref> | *The [[Loop of Henle|thick ascending limb of the loop of Henle]] is not permeable to water and reabsorbs a large proportion of the filtered [[sodium chloride]] as shown in figure, which leads to interstitial hypertonicity that powers the [[countercurrent exchange]] and urinary concentration mechanisms. In case of impairment of this function, a major loss of [[water]] and [[sodium]] occurs, as seen with [[Loop diuretic|loop diuretics]].<ref name="pmid21503667">{{cite journal| author=Seyberth HW, Schlingmann KP| title=Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects. | journal=Pediatr Nephrol | year= 2011 | volume= 26 | issue= 10 | pages= 1789-802 | pmid=21503667 | doi=10.1007/s00467-011-1871-4 | pmc=3163795 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21503667 }} </ref> | ||
*Bartter syndrome is a renal tubular salt-wasting disorder in which the kidneys cannot reabsorb sodium and chloride in the thick ascending limb of the loop of Henle. | *[[Bartter syndrome]] is a [[Renal tubular disorder|renal tubular salt-wasting disorder]] in which the kidneys cannot reabsorb [[sodium]] and [[chloride]] in the [[Loop of Henle|thick ascending limb of the loop of Henle]]. | ||
*Impairment of sodium and chloride reabsorption is the primary defect in the Bartter syndrome that initiates the cascade. | *Impairment of [[sodium]] and [[chloride]] reabsorption is the primary defect in the [[Bartter syndrome]] that initiates the cascade. | ||
*This leads to increased delivery of salt to the distal tubules and excessive salt and water loss from the body. The resultant volume depletion causes activation of the renin-angiotensin-aldosterone system (RAAS) and subsequent secondary hyperaldosteronism. Long-term stimulation causes hyperplasia of the juxtaglomerular apparatus and elevates renin levels.<ref name="pmid21941653">{{cite journal| author=Deschênes G, Fila M| title=Primary molecular disorders and secondary biological adaptations in bartter syndrome. | journal=Int J Nephrol | year= 2011 | volume= 2011 | issue= | pages= 396209 | pmid=21941653 | doi=10.4061/2011/396209 | pmc=3177086 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21941653 }} </ref><ref name="pmid13969763">{{cite journal| author=BARTTER FC, PRONOVE P, GILL JR, MACCARDLE RC| title=Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndrome. | journal=Am J Med | year= 1962 | volume= 33 | issue= | pages= 811-28 | pmid=13969763 | doi=10.1016/0002-9343(62)90214-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13969763 }} </ref> | *This leads to increased delivery of salt to the [[Distal convoluted tubule|distal tubules]] and excessive salt and water loss from the body. The resultant volume depletion causes activation of the [[Renin-angiotensin system|renin-angiotensin-aldosterone system (RAAS)]] and subsequent [[Hyperaldosteronism|secondary hyperaldosteronism]]. Long-term stimulation causes hyperplasia of the [[juxtaglomerular apparatus]] and elevates [[Renin|renin levels]].<ref name="pmid21941653">{{cite journal| author=Deschênes G, Fila M| title=Primary molecular disorders and secondary biological adaptations in bartter syndrome. | journal=Int J Nephrol | year= 2011 | volume= 2011 | issue= | pages= 396209 | pmid=21941653 | doi=10.4061/2011/396209 | pmc=3177086 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21941653 }} </ref><ref name="pmid13969763">{{cite journal| author=BARTTER FC, PRONOVE P, GILL JR, MACCARDLE RC| title=Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndrome. | journal=Am J Med | year= 1962 | volume= 33 | issue= | pages= 811-28 | pmid=13969763 | doi=10.1016/0002-9343(62)90214-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13969763 }} </ref> | ||
*Excessive distal delivery of sodium follows by sodium (Na) reabsorption in the distal convoluted tubule. Na reabsorption exchange with the secretion of positively charged potassium or hydrogen ion and leads to increased loss of potassium (K+) in urine and increased hydrogen (H+) secretion. | *Excessive distal delivery of [[sodium]] follows by [[sodium]] (Na) reabsorption in the [[distal convoluted tubule]]. [[Na+-exporting ATPase|Na]] reabsorption exchange with the secretion of positively charged [[potassium]] or [[hydrogen]] ion and leads to increased loss of [[potassium]] (K+) in urine and increased [[Hydrogen|hydrogen (H+)]] secretion. | ||
*Decreased chloride (Cl-) reabsorption decreases the exchange with bicarbonate (HCO3-). Thus, increased bicarbonate retention and hypokalemia result in metabolic alkalosis.<ref name="pmid30851722">{{cite journal| author=Soylu Ustkoyuncu P, Nalcacioglu H, Bastug F, Yel S, Altuner Torun Y| title=Association of Mucopolysaccharidosis Type 4A and Bartter Syndrome. | journal=Iran J Kidney Dis | year= 2019 | volume= 13 | issue= 1 | pages= 71-72 | pmid=30851722 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30851722 }} </ref> | *Decreased [[Chloride|chloride (Cl-)]] reabsorption decreases the exchange with [[bicarbonate]] (HCO3-). Thus, increased [[bicarbonate]] retention and [[hypokalemia]] result in [[metabolic alkalosis]].<ref name="pmid30851722">{{cite journal| author=Soylu Ustkoyuncu P, Nalcacioglu H, Bastug F, Yel S, Altuner Torun Y| title=Association of Mucopolysaccharidosis Type 4A and Bartter Syndrome. | journal=Iran J Kidney Dis | year= 2019 | volume= 13 | issue= 1 | pages= 71-72 | pmid=30851722 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30851722 }} </ref> | ||
*Defective sodium reabsorption in the loop of Henle impairs the concentration of urine as water follows sodium.<ref name="pmid26140272">{{cite journal| author=Al Shibli A, Narchi H| title=Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations. | journal=World J Methodol | year= 2015 | volume= 5 | issue= 2 | pages= 55-61 | pmid=26140272 | doi=10.5662/wjm.v5.i2.55 | pmc=4482822 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26140272 }} </ref> | *Defective [[Sodium|sodium reabsorption]] in the [[loop of Henle]] impairs the concentration of urine as [[water]] follows [[sodium]].<ref name="pmid26140272">{{cite journal| author=Al Shibli A, Narchi H| title=Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations. | journal=World J Methodol | year= 2015 | volume= 5 | issue= 2 | pages= 55-61 | pmid=26140272 | doi=10.5662/wjm.v5.i2.55 | pmc=4482822 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26140272 }} </ref> | ||
*Calcium and magnesium reabsorb in the ascending limb of the loop of Henle as a result of a positive electrochemical gradient in the lumen created by the back leak of K+ ion in the lumen, pushes these ions into the cells as shown in the figure. The defective sodium chloride transport in the ascending limb of the loop of Henle associated with Bartter syndrome leads to the impaired electrochemical gradient leading to increased urinary loss of calcium and magnesium. This leads to the development of nephrocalcinosis in Bartter syndrome.<ref name="pmid18695706">{{cite journal| author=Seyberth HW| title=An improved terminology and classification of Bartter-like syndromes. | journal=Nat Clin Pract Nephrol | year= 2008 | volume= 4 | issue= 10 | pages= 560-7 | pmid=18695706 | doi=10.1038/ncpneph0912 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18695706 }} </ref> | *[[Calcium]] and [[magnesium]] reabsorb in the [[Loop of Henle|ascending limb of the loop of Henle]] as a result of a [[Electrochemical gradient|positive electrochemical gradient]] in the lumen created by the [[Potassium ion channels|back leak of K+ ion]] in the lumen, pushes these ions into the cells as shown in the figure. The defective [[sodium chloride]] transport in the [[Loop of Henle|ascending limb of the loop of Henle]] associated with [[Bartter syndrome]] leads to the impaired [[electrochemical gradient]] leading to increased urinary loss of [[calcium]] and [[magnesium]]. This leads to the development of [[nephrocalcinosis]] in [[Bartter syndrome]].<ref name="pmid18695706">{{cite journal| author=Seyberth HW| title=An improved terminology and classification of Bartter-like syndromes. | journal=Nat Clin Pract Nephrol | year= 2008 | volume= 4 | issue= 10 | pages= 560-7 | pmid=18695706 | doi=10.1038/ncpneph0912 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18695706 }} </ref> | ||
[[File:Bartter Syndrome.PNG|600px|center]] | [[File:Bartter Syndrome.PNG|600px|center]] | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]
Overview
Pathophysiology
- The thick ascending limb of the loop of Henle is not permeable to water and reabsorbs a large proportion of the filtered sodium chloride as shown in figure, which leads to interstitial hypertonicity that powers the countercurrent exchange and urinary concentration mechanisms. In case of impairment of this function, a major loss of water and sodium occurs, as seen with loop diuretics.[1]
- Bartter syndrome is a renal tubular salt-wasting disorder in which the kidneys cannot reabsorb sodium and chloride in the thick ascending limb of the loop of Henle.
- Impairment of sodium and chloride reabsorption is the primary defect in the Bartter syndrome that initiates the cascade.
- This leads to increased delivery of salt to the distal tubules and excessive salt and water loss from the body. The resultant volume depletion causes activation of the renin-angiotensin-aldosterone system (RAAS) and subsequent secondary hyperaldosteronism. Long-term stimulation causes hyperplasia of the juxtaglomerular apparatus and elevates renin levels.[2][3]
- Excessive distal delivery of sodium follows by sodium (Na) reabsorption in the distal convoluted tubule. Na reabsorption exchange with the secretion of positively charged potassium or hydrogen ion and leads to increased loss of potassium (K+) in urine and increased hydrogen (H+) secretion.
- Decreased chloride (Cl-) reabsorption decreases the exchange with bicarbonate (HCO3-). Thus, increased bicarbonate retention and hypokalemia result in metabolic alkalosis.[4]
- Defective sodium reabsorption in the loop of Henle impairs the concentration of urine as water follows sodium.[5]
- Calcium and magnesium reabsorb in the ascending limb of the loop of Henle as a result of a positive electrochemical gradient in the lumen created by the back leak of K+ ion in the lumen, pushes these ions into the cells as shown in the figure. The defective sodium chloride transport in the ascending limb of the loop of Henle associated with Bartter syndrome leads to the impaired electrochemical gradient leading to increased urinary loss of calcium and magnesium. This leads to the development of nephrocalcinosis in Bartter syndrome.[6]
References
- ↑ Seyberth HW, Schlingmann KP (2011). "Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects". Pediatr Nephrol. 26 (10): 1789–802. doi:10.1007/s00467-011-1871-4. PMC 3163795. PMID 21503667.
- ↑ Deschênes G, Fila M (2011). "Primary molecular disorders and secondary biological adaptations in bartter syndrome". Int J Nephrol. 2011: 396209. doi:10.4061/2011/396209. PMC 3177086. PMID 21941653.
- ↑ BARTTER FC, PRONOVE P, GILL JR, MACCARDLE RC (1962). "Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndrome". Am J Med. 33: 811–28. doi:10.1016/0002-9343(62)90214-0. PMID 13969763.
- ↑ Soylu Ustkoyuncu P, Nalcacioglu H, Bastug F, Yel S, Altuner Torun Y (2019). "Association of Mucopolysaccharidosis Type 4A and Bartter Syndrome". Iran J Kidney Dis. 13 (1): 71–72. PMID 30851722.
- ↑ Al Shibli A, Narchi H (2015). "Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations". World J Methodol. 5 (2): 55–61. doi:10.5662/wjm.v5.i2.55. PMC 4482822. PMID 26140272.
- ↑ Seyberth HW (2008). "An improved terminology and classification of Bartter-like syndromes". Nat Clin Pract Nephrol. 4 (10): 560–7. doi:10.1038/ncpneph0912. PMID 18695706.