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{{Metabolic alkalosis}}
{{Metabolic alkalosis}}


{{CMG}}; {{AE}}  
{{CMG}}; {{AE}} {{MMT}}
==Overview==
==Overview==
The normal [[physiological]] pH of [[blood]] is 7.35 to 7.45. An increase above this range is known to be [[Alkalosis]]. [[Metabolic Alkalosis]] is defined as a [[disease]] state where [[blood pH]] is more than 7.45 due to secondary metabolic processes. The primary [[PH buffer|pH]] buffers in maintaining [[chemical equilibrium]] of physiological [[Blood pH]] are [[alkaline]] [[Bicarbonate|Bicarbonate ions(HCO3]]) and [[acidic]] [[Carbon dioxide|carbon dioxide(CO2)]]. When there is increase amount of [[Bicarbonate|Bicarbonate(HCO3)]] in body or decrease amount of [[carbon dioxide]] or loss of [[hydrogen ions]] it causes [[alkalosis]].  [[Metabolic alkalosis]] occurs due to trapping of [[Bicarbonate|Bicarbonate ions]] (HCO3) or loss of [[hydrogen ions]] in body due to some [[metabolic]] causes for example- [[Gastrointestinal|gastrointestinal loss]] of [[hydrogen ions]], [[Intracellular|intracellular shifting]] of [[hydrogen ions]], [[renal]] [[hydrogen]] loss, increased [[Bicarbonate|bicarbonate ions]] in [[extracellular]] [[Compartments|compartment]], [[Diuretic|diuretic i]]<nowiki/>nduced [[alkalosis]] or [[contraction alkalosis]]. Patient with normal [[renal physiology]] will compensate this increase amount of [[bicarbonate]] through excretion. But impaired [[renal function]] [[secondary]] to [[Chloride|chloride depletion]], [[hypokalemia]], [[hyperaldosteronism]], reduced [[Glomerular filtration rate|glomerular function rate]], reduced [[Effective circulating volume|effective arterial blood volume]] ([[EABV|EABV)]]) in [[heart failure]] or [[cirrhosis]] will lead to [[metabolic alkalosis]]. When the [[physiologic]] [[blood pH]] is above 7.45, it triggers [[Respiratory centre of the medulla|respiratory center]] to cause [[hypoventilation]], thus decreased [[Carbon dioxide|PCO2]] leading to [[Compensatory responses for acid-base disorders|compensatory]] [[respiratory acidosis]]. The [[Carbon dioxide|PCO2]] increases about 0.5 to 0.7 mmHg to every 1.0 mM increase in [[Bicarbonate|plasma bicarbonate concentration]]. In severe [[Metabolic alkalosis]] [[Carbon dioxide|PCO2]] can reach 60 mmHg. The [[mortality rate]] with [[metabolic alkalosis]] is 45% with [[Arterial blood ph|arterial blood pH]] 7.55 to 80% with arterial blood pH of 7.65. [[Treatment]] is usually supportive based on cause of the [[Disease|disease.]]
The normal [[physiological]] pH of [[blood]] is 7.35 to 7.45. An increase above this range is known to be [[Alkalosis]]. [[Metabolic Alkalosis]] is defined as a [[disease]] state where [[blood pH]] is more than 7.45 due to secondary metabolic processes. The primary [[PH buffer|pH]] buffers in maintaining [[chemical equilibrium]] of physiological [[Blood pH]] are [[alkaline]] [[Bicarbonate|Bicarbonate ions(HCO3]]) and [[acidic]] [[Carbon dioxide|carbon dioxide(CO2)]]. When there is increase amount of [[Bicarbonate|Bicarbonate(HCO3)]] in body or decrease amount of [[carbon dioxide]] or loss of [[hydrogen ions]] it causes [[alkalosis]].  [[Metabolic alkalosis]] occurs due to trapping of [[Bicarbonate|Bicarbonate ions]] (HCO3) or loss of [[hydrogen ions]] in body due to some [[metabolic]] causes for example- [[Gastrointestinal|gastrointestinal loss]] of [[hydrogen ions]], [[Intracellular|intracellular shifting]] of [[hydrogen ions]], [[renal]] [[hydrogen]] loss, increased [[Bicarbonate|bicarbonate ions]] in [[extracellular]] [[Compartments|compartment]], [[Diuretic|diuretic i]]<nowiki/>nduced [[alkalosis]] or [[contraction alkalosis]]. Patient with normal [[renal physiology]] will compensate this increase amount of [[bicarbonate]] through excretion. But impaired [[renal function]] [[secondary]] to [[Chloride|chloride depletion]], [[hypokalemia]], [[hyperaldosteronism]], reduced [[Glomerular filtration rate|glomerular function rate]], reduced [[Effective circulating volume|effective arterial blood volume]] ([[EABV|EABV)]]) in [[heart failure]] or [[cirrhosis]] will lead to [[metabolic alkalosis]]. When the [[physiologic]] [[blood pH]] is above 7.45, it triggers [[Respiratory centre of the medulla|respiratory center]] to cause [[hypoventilation]], thus decreased [[Carbon dioxide|PCO2]] leading to [[Compensatory responses for acid-base disorders|compensatory]] [[respiratory acidosis]]. The [[Carbon dioxide|PCO2]] increases about 0.5 to 0.7 mmHg to every 1.0 mM increase in [[Bicarbonate|plasma bicarbonate concentration]]. In severe [[Metabolic alkalosis]] [[Carbon dioxide|PCO2]] can reach 60 mmHg. The [[mortality rate]] with [[metabolic alkalosis]] is 45% with [[Arterial blood ph|arterial blood pH]] 7.55 to 80% with arterial blood pH of 7.65. [[Treatment]] is usually supportive based on cause of the [[Disease|disease.]]
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===Loss of hydrogen ions===
===Loss of hydrogen ions===
====GI loss====
====GI loss====
* [[Vomiting]] (excretion of hydrogen ions and the retention of bicarbonate)
[[Vomiting]] (most commonly seen in [[pyloric stenosis]]), [[Nasogastric tube|NG suction]] , [[Zollinger-Ellison syndrome|Zollinger-ellison]] syndrome, [[Bulimia nervosa|Bulimia]].<ref name="pmid1928424">{{cite journal |vauthors=Galla JH, Gifford JD, Luke RG, Rome L |title=Adaptations to chloride-depletion alkalosis |journal=Am J Physiol |volume=261 |issue=4 Pt 2 |pages=R771–81 |date=October 1991 |pmid=1928424 |doi=10.1152/ajpregu.1991.261.4.R771 |url=}}</ref>
* [[Nasogastric tube]] suction
**[[Diuretic|Diuretics]]: [[Loop diuretic|Loop]] and [[thiazide diuretics]].
**[[Diarrhea]]: [[Villous adenoma]]<ref name="pmid5927076">{{cite journal |vauthors=Babior BM |title=Villous adenoma of the colon. Study of a patient with severe fluid and electrolyte disturbances |journal=Am J Med |volume=41 |issue=4 |pages=615–21 |date=October 1966 |pmid=5927076 |doi=10.1016/0002-9343(66)90223-3 |url=}}</ref>, [[congenital chloride diarrhea]]<ref name="pmid8896562">{{cite journal |vauthors=Höglund P, Haila S, Socha J, Tomaszewski L, Saarialho-Kere U, Karjalainen-Lindsberg ML, Airola K, Holmberg C, de la Chapelle A, Kere J |title=Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea |journal=Nat Genet |volume=14 |issue=3 |pages=316–9 |date=November 1996 |pmid=8896562 |doi=10.1038/ng1196-316 |url=}}</ref>
**[[Cystic fibrosis]].<ref name="pmid7618650">{{cite journal |vauthors=Pedroli G, Liechti-Gallati S, Mauri S, Birrer P, Kraemer R, Foletti-Jäggi C, Bianchetti MG |title=Chronic metabolic alkalosis: not uncommon in young children with severe cystic fibrosis |journal=Am J Nephrol |volume=15 |issue=3 |pages=245–50 |date=1995 |pmid=7618650 |doi=10.1159/000168839 |url=}}</ref>
**[[Chloride]] deficient [[Infant formula|infant formula.]]
**Gastrocystoplasty <ref name="pmid7609133">{{cite journal |vauthors=Plawker MW, Rabinowitz SS, Etwaru DJ, Glassberg KI |title=Hypergastrinemia, dysuria-hematuria and metabolic alkalosis: complications associated with gastrocystoplasty |journal=J Urol |volume=154 |issue=2 Pt 1 |pages=546–9 |date=August 1995 |pmid=7609133 |doi=10.1097/00005392-199508000-00066 |url=}}</ref>
**Post hypercapneic [[metabolic alkalosis]].
====Renal====
====Renal====
* Over-[[diuresis]]
**Dietary [[potassium]] depletion.<ref name="pmid8648937">{{cite journal |vauthors=Sabatini S |title=The cellular basis of metabolic alkalosis |journal=Kidney Int |volume=49 |issue=3 |pages=906–17 |date=March 1996 |pmid=8648937 |doi=10.1038/ki.1996.125 |url=}}</ref>
* [[Hyperaldosteronism]] causing retention of sodium followed with compensatory excretion of hydrogen
**[[Primary Hyperaldosteronism|Primary hyperaldosteronism]]: [[Conn syndrome]] or [[adenoma]], [[hyperplasia]], [[carcinoma]], [[renin]] or [[glucocorticoid]] responsive.
* Administration of non-resorbable anions such as, [[penicillin]], [[carbenicillin]], which complexs with positively-charged hydrogen ions in the [[renal tubules]].
**[[Secondary hyperaldosteronism]]: [[Renovascular hypertension|Reno vascular hypertension]], [[edema]] ([[cirrhosis]], [[heart failure]], [[Nephrotic syndrome|nephrotic syndrome)]], [[Juxtaglomerular apparatus|juxtaglomerular cell]]([[Renin-secreting tumors|renin producing) tumor]], [[renal cell carcinoma]], [[hemangiopericytoma]], [[nephroblastoma]]
**[[Mineralocorticoid]] excess due to primary decorticosterone excess ([[11β-hydroxylase deficiency|11 beta]], [[17 alpha-hydroxylase deficiency|17 alpha hydroxylase deficienc]]<nowiki/>y), [[licorice]]([[glycyrrhetinic acid]]), [[Liddle's syndrome|liddle syndrome]].<ref name="pmid1731223">{{cite journal |vauthors=Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S, Lalouel JM |title=A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension |journal=Nature |volume=355 |issue=6357 |pages=262–5 |date=January 1992 |pmid=1731223 |doi=10.1038/355262a0 |url=}}</ref> <ref name="pmid9452995">{{cite journal |vauthors=Warnock DG |title=Liddle syndrome: an autosomal dominant form of human hypertension |journal=Kidney Int |volume=53 |issue=1 |pages=18–24 |date=January 1998 |pmid=9452995 |doi=10.1046/j.1523-1755.1998.00728.x |url=}}</ref>
**[[Bartter syndrome|Bartter]] and [[Gitelman syndrome]]. <ref name="pmid9767561">{{cite journal |vauthors=Kurtz I |title=Molecular pathogenesis of Bartter's and Gitelman's syndromes |journal=Kidney Int |volume=54 |issue=4 |pages=1396–410 |date=October 1998 |pmid=9767561 |doi=10.1046/j.1523-1755.1998.00124.x |url=}}</ref>


===Increase in the serum bicarbonate===
===Increase in the serum bicarbonate===
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==Genetics==
==Genetics==
*[Disease name] is transmitted in [mode of genetic transmission] pattern.
 
*Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
*Genes involved in the pathogenesis of Metabolic Alkalosis include CFTR, SCNN1B/SCNN1G, NKCC2<ref name="pmid8841184">{{cite journal |vauthors=Simon DB, Karet FE, Rodriguez-Soriano J, Hamdan JH, DiPietro A, Trachtman H, Sanjad SA, Lifton RP |title=Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK |journal=Nat Genet |volume=14 |issue=2 |pages=152–6 |date=October 1996 |pmid=8841184 |doi=10.1038/ng1096-152 |url=}}</ref> SLC12A3/CLCNKB and SLC26A3 <ref name="pmid31145360">{{cite journal |vauthors=Kamal NM, Khan HY, El-Shabrawi MHF, Sherief LM |title=Congenital chloride losing diarrhea: A single center experience in a highly consanguineous population |journal=Medicine (Baltimore) |volume=98 |issue=22 |pages=e15928 |date=May 2019 |pmid=31145360 |pmc=6709049 |doi=10.1097/MD.0000000000015928 |url=}}</ref> causing Cystic Fibrosis, Liddle Syndrome, Bartter syndrome, Gitelman syndrome and Congenital Chloride Diarrhhea respectively.
*The development of [disease name] is the result of multiple genetic mutations.
 


==Associated Conditions==
==Associated Conditions==

Revision as of 03:06, 1 February 2021

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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

The normal physiological pH of blood is 7.35 to 7.45. An increase above this range is known to be Alkalosis. Metabolic Alkalosis is defined as a disease state where blood pH is more than 7.45 due to secondary metabolic processes. The primary pH buffers in maintaining chemical equilibrium of physiological Blood pH are alkaline Bicarbonate ions(HCO3) and acidic carbon dioxide(CO2). When there is increase amount of Bicarbonate(HCO3) in body or decrease amount of carbon dioxide or loss of hydrogen ions it causes alkalosis. Metabolic alkalosis occurs due to trapping of Bicarbonate ions (HCO3) or loss of hydrogen ions in body due to some metabolic causes for example- gastrointestinal loss of hydrogen ions, intracellular shifting of hydrogen ions, renal hydrogen loss, increased bicarbonate ions in extracellular compartment, diuretic induced alkalosis or contraction alkalosis. Patient with normal renal physiology will compensate this increase amount of bicarbonate through excretion. But impaired renal function secondary to chloride depletion, hypokalemia, hyperaldosteronism, reduced glomerular function rate, reduced effective arterial blood volume (EABV)) in heart failure or cirrhosis will lead to metabolic alkalosis. When the physiologic blood pH is above 7.45, it triggers respiratory center to cause hypoventilation, thus decreased PCO2 leading to compensatory respiratory acidosis. The PCO2 increases about 0.5 to 0.7 mmHg to every 1.0 mM increase in plasma bicarbonate concentration. In severe Metabolic alkalosis PCO2 can reach 60 mmHg. The mortality rate with metabolic alkalosis is 45% with arterial blood pH 7.55 to 80% with arterial blood pH of 7.65. Treatment is usually supportive based on cause of the disease.

Pathophysiology

Loss of hydrogen ions

GI loss

Vomiting (most commonly seen in pyloric stenosis), NG suction , Zollinger-ellison syndrome, Bulimia.[1]

Renal

Increase in the serum bicarbonate

Shift of hydrogen ions into intracellular space

  • Seen in hypokalemia. Due to a low extracellular potassium concentration, potassium shifts out of the cells, and in order to maintain electrical neutrality, hydrogen shifts into the cells, leaving behind bicarbonate.

Contraction alkalosis

  • This results from a loss of water in the extracellular space which is poor in bicarbonate, typically from diuretic use. Since water is lost while bicarbonate is retained, the concentration of bicarbonate increases.

Compensation for Metabolic Alkalosis

  • The body attempts to compensate for the increase in pH by retaining carbon dioxide (CO2) through hypoventilation (respiratory compensation). CO2 combines with elements in the bloodstream to form carbonic acid, thus decreasing pH.
  • The pCO2 rises 0.5 - 1 for every 1 unit increase in serum HCO3 from a baseline of 24.
  • The maximum pCO2 in compensation is 55-60.
  • Renal compensation for metabolic alkalosis consists of increased excretion of HCO3- (bicarbonate), because the filtered load of HCO3- exceeds the ability of the renal tubule to reabsorb it.

Genetics

  • Genes involved in the pathogenesis of Metabolic Alkalosis include CFTR, SCNN1B/SCNN1G, NKCC2[10] SLC12A3/CLCNKB and SLC26A3 [11] causing Cystic Fibrosis, Liddle Syndrome, Bartter syndrome, Gitelman syndrome and Congenital Chloride Diarrhhea respectively.


Associated Conditions

Gross Pathology

  • On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology

  • On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

References

  1. ↑ Galla JH, Gifford JD, Luke RG, Rome L (October 1991). "Adaptations to chloride-depletion alkalosis". Am J Physiol. 261 (4 Pt 2): R771–81. doi:10.1152/ajpregu.1991.261.4.R771. PMID 1928424.
  2. ↑ Babior BM (October 1966). "Villous adenoma of the colon. Study of a patient with severe fluid and electrolyte disturbances". Am J Med. 41 (4): 615–21. doi:10.1016/0002-9343(66)90223-3. PMID 5927076.
  3. ↑ Höglund P, Haila S, Socha J, Tomaszewski L, Saarialho-Kere U, Karjalainen-Lindsberg ML, Airola K, Holmberg C, de la Chapelle A, Kere J (November 1996). "Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea". Nat Genet. 14 (3): 316–9. doi:10.1038/ng1196-316. PMID 8896562.
  4. ↑ Pedroli G, Liechti-Gallati S, Mauri S, Birrer P, Kraemer R, Foletti-Jäggi C, Bianchetti MG (1995). "Chronic metabolic alkalosis: not uncommon in young children with severe cystic fibrosis". Am J Nephrol. 15 (3): 245–50. doi:10.1159/000168839. PMID 7618650.
  5. ↑ Plawker MW, Rabinowitz SS, Etwaru DJ, Glassberg KI (August 1995). "Hypergastrinemia, dysuria-hematuria and metabolic alkalosis: complications associated with gastrocystoplasty". J Urol. 154 (2 Pt 1): 546–9. doi:10.1097/00005392-199508000-00066. PMID 7609133.
  6. ↑ Sabatini S (March 1996). "The cellular basis of metabolic alkalosis". Kidney Int. 49 (3): 906–17. doi:10.1038/ki.1996.125. PMID 8648937.
  7. ↑ Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S, Lalouel JM (January 1992). "A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension". Nature. 355 (6357): 262–5. doi:10.1038/355262a0. PMID 1731223.
  8. ↑ Warnock DG (January 1998). "Liddle syndrome: an autosomal dominant form of human hypertension". Kidney Int. 53 (1): 18–24. doi:10.1046/j.1523-1755.1998.00728.x. PMID 9452995.
  9. ↑ Kurtz I (October 1998). "Molecular pathogenesis of Bartter's and Gitelman's syndromes". Kidney Int. 54 (4): 1396–410. doi:10.1046/j.1523-1755.1998.00124.x. PMID 9767561.
  10. ↑ Simon DB, Karet FE, Rodriguez-Soriano J, Hamdan JH, DiPietro A, Trachtman H, Sanjad SA, Lifton RP (October 1996). "Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK". Nat Genet. 14 (2): 152–6. doi:10.1038/ng1096-152. PMID 8841184.
  11. ↑ Kamal NM, Khan HY, El-Shabrawi M, Sherief LM (May 2019). "Congenital chloride losing diarrhea: A single center experience in a highly consanguineous population". Medicine (Baltimore). 98 (22): e15928. doi:10.1097/MD.0000000000015928. PMC 6709049 Check |pmc= value (help). PMID 31145360. Vancouver style error: initials (help)

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