Metabolic alkalosis resident survival guide: Difference between revisions
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{{SK}} | {{WikiDoc CMG}}; {{AE}} {{MMT}} | ||
{{SK}} Approach to Metabolic alkalosis, Metabolic alkalosis management, Metabolic alkalosis work-up | |||
==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 the [[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 an increased amount of [[Bicarbonate|Bicarbonate(HCO3)]] in the body or a decreased amount of [[carbon dioxide]] or a loss of [[hydrogen ions]], it causes [[alkalosis]]. [[Metabolic alkalosis]] occurs due to the trapping of [[Bicarbonate|Bicarbonate ions]] (HCO3) or loss of [[hydrogen ions]] in the 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 increased 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 the [[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 [[PCO2]]elevates from 0.5 to 0.7 mmHg per 1.0 [[mill mole]] elevation 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. | |||
==Causes== | ==Causes== | ||
===Life Threatening Causes=== | ===Life Threatening Causes=== | ||
Life-threatening causes | Life-threatening causes of severe [[Metabolic alkalosis|metabolic alkalosis (]]<nowiki/>pH 7.55 to 7.65) may result in death (45% to 80%) or permanent disability within 24 hours if left untreated.<ref name="pmid20436691">{{cite journal |vauthors=Tripathy S |title=Extreme metabolic alkalosis in intensive care |journal=Indian J Crit Care Med |volume=13 |issue=4 |pages=217–20 |date=October 2009 |pmid=20436691 |pmc=2856150 |doi=10.4103/0972-5229.60175 |url=}}</ref> | ||
* [[ | |||
* [[ | *[[Gastric acidity reduced|Loss of gastric acid]] | ||
*[[Loop diuretics|Loop]] or [[thiazide diuretics]] | |||
===Common Causes=== | ===Common Causes=== | ||
* [[ | |||
* [[ | *'''[[Chloride]] depletion''' o[[Gastrointestinal|r '''Gastrointestinal''']] '''loss of [[hydrogen]]''' | ||
* [[ | **[[Gastrointestinal tract|GI]] loss: [[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> | ||
* [[ | **[[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]]. | |||
*'''[[Potassium]] depletion''' or '''[[Mineralocorticoids]] excess''' or '''[[Renal]] loss of [[hydrogen]]''' | |||
**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> | |||
**[[Primary Hyperaldosteronism|Primary hyperaldosteronism]]: [[Conn syndrome]] or [[adenoma]], [[hyperplasia]], [[carcinoma]], [[renin]] or [[glucocorticoid]] responsive. | |||
**[[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> | |||
**[[Laxative]] | |||
*'''Reduced [[Glomerular filtration rate]]''' | |||
**[[Chronic kidney disease]] | |||
*'''[[Extracellular fluid|ECF volume]] depletion/ [[Volume depletion|Volume contraction]]''' | |||
**[[Hypovolemia]] or [[Diuresis|massive diuresis]] with [[loop diuretics]]. | |||
*'''Miscellanous''' | |||
**[[Hypercalcemia]] due to [[Milk-alkali syndrome]] or [[bone metastasis]]. | |||
**Massive [[blood transfusion]]. | |||
**[[Acetate]] containing [[Colloid|colloid sollution]]. | |||
**[[Exogenous]] [[alkali]] admintration. | |||
**Combined [[antacid]] and cation exchange resin administration. | |||
**Sodium [[Penicillin|penicillins]]. | |||
==Diagnosis== | ==Diagnosis== | ||
Shown below is an algorithm summarizing the diagnosis of < | Shown below is an [[algorithm]] summarizing the [[diagnosis]] and [[treatment]] of [[Metabolic alkalosis|Metabolic Alkalosis]].<ref name="pmid20436691">{{cite journal |vauthors=Tripathy S |title=Extreme metabolic alkalosis in intensive care |journal=Indian J Crit Care Med |volume=13 |issue=4 |pages=217–20 |date=October 2009 |pmid=20436691 |pmc=2856150 |doi=10.4103/0972-5229.60175 |url=}}</ref> | ||
{{familytree | {{familytree/start |summary=Sample 1}} | ||
{{familytree | | | | | {{familytree | | | | | | | | | | | | A01 | | | | | |A01='''History''': • H/O [[Cystic fibrosis]]/[[Congenital adrenal hyperplasia]]/[[CHF]]/[[Uncontrolled HTN]]?<br>• Excess [[antacid]] consumption?<br>• [[Calcium]] over supplementation?<br>• [[Beta lactum antibiotic]] use?<br>• Recent or current [[diuretic]] use?<br>• [[Vomiting]] or [[diarrhea]]?<br>• massive use of [[licorice]]?<br>• H/O recent [[hypercapneic]] [[respiratory failure]]?}} | ||
{{familytree | | | | |!| | | | }} | {{familytree | | | | | | | | | | | | |!| | | | | | | | }} | ||
{{familytree | | | | | {{familytree | | | | | | | | | | | | B01 | | | | | |B01='''Physical Examination''': •'''General [[appearance]]''': [[Restlessness]]/ [[Irritable]]/[[lethargic]]?<br>• '''[[Skin]]''': decreased or normal [[turgor]]?<br>• '''[[HEENT]]''': [[Headache]]/[[Dizziness]]?<br>• '''[[CVS]]''': [[Dysrhythmia]]/[[Tachycardia]]?<br>• '''[[Respiratory]]''': [[Hypoxemia]], [[Compensatory]] [[hypoventilation]], [[Pulmonary]] [[microatelactasis]], Increased [[V/Q mismatch]]<br>• '''[[GI]]''': [[Nausea]]/[[vomiting]]/[[diarrhea]]?<br>• '''[[GU]]''': [[Urine output]], [[frequency]]?<br>• '''[[CNS]]''': [[Confusion]], loss of [[consciousness]]/[[Mental obtundation]], [[Neuromuscular excitability]]/[[Muscle cramps]], [[Tremor]], [[tingling]] and [[numbness]] in [[extremities]], [[Weakness]]? }} | ||
{{familytree | | |,|-|^|-|.| | }} | {{familytree | | | | | | | | | | | | |!| | | | | | | | }} | ||
{{familytree | | | {{familytree | | | | | | | | | | | | C01 | | | | | |C01='''[[Laboratory Tests]]''' •[[ABG]](pH >7.45, [[HCO3]] >26 mEq/L, [[PCO2]] compensates for increased [[HCO3]] by decreasing)<br>• [[Basic metabolic panel]]<br>• [[Serum Aldosterone]] And [[renin]]<br>• [[Urine analysis]], [[Urine pH]], [[Urine Chloride]] and [[sodium]]<br>• [[Chest]] [[X-ray]]<br>• [[Abdominal]] [[USG]]/[[CT]] to rule out [[mass]]}} | ||
{{familytree | | | | | |,|-|-|-|-|-|-|+|-|-|-|-|-|-|.| }} | |||
{{familytree | | | | | D01 | | | | | D02 | | | | | D03 |D01='''Expanded [[EABV]](No sign of [[volume depletion]] or [[Saline]] unresponsive)''' •'''[[Treatment]]''': Treat underlying cause.|D02='''Contracted [[EABV]](sign of [[volume depletion]] or [[saline]] responsive)''' •'''[[Treatment]]''': Replace [[volume]] with [[NaCl]] if depleted, correct [[electrolyte imbalance]], reduction of [[gastric secretion]] by [[H2 blocker]] or [[PPI]], discontinue [[diuretics]], [[Acetazolamide]], [[NH4Cl]] and [[HCl]] should be reserved for severe cases. |D03='''Rule out by [[history]]''' •'''[[Treatment]]''': According to cause with discontinuation of offending agents. }} | |||
{{familytree | | | | | |!| | | | | | |!| | |,|-|-|-|^|-|-|-|-|.|}} | |||
{{familytree | | | | | |!| | | | | | |!| | E01 | | | | | | | E02 |E01=[[Transient]]|E02=[[Renal failure]] with ingestion}} | |||
{{familytree | | | | | |!| | | | | | |!| | |!| | | | | | | | |!| | }} | |||
{{familytree | | | | | |!| | | | | | |!| | F01 | | | | | | | F02 |F01=• [[IV]] [[HCO3]]<br>• Acute correction of [[hypercapnea]]|F02=• [[Milk-alkali syndrome]]<br>• [[HCO3]] ingesion }} | |||
{{familytree | | | | | |!| | |,|-|-|-|^|-|-|-|-|.|}} | |||
{{familytree | | | | | |!| | G01 | | | | | | | G02 |G01='''[[GI]] loss(low [[urine Cl]])'''|G02='''[[Renal]] loss(high [[urine Cl]])'''}} | |||
{{familytree | | | | | |!| | |!| | | | | | | | |!| | }} | |||
{{familytree | | | | | |!| | H01 | | | | | | | H02 |H01=• '''[[Gastric]]''': [[Vomiting]], [[NG suction]]<br>• '''[[Lower]] [[bowel]]''': [[Villous adenoma]], [[chloridorrhea]], [[laxative]] abuse|H02=• [[Non-reabsorbed]] ions: [[Penicillin]]<br>• ='''Impaired [[tubular]] [[transport]]''': [[Loop]] and [[thiazide diuretics]], [[Barrter's]] and [[Gitelman's]] disease, [[Hypomagnesaemia]] }} | |||
{{familytree | |,|-|-|-|+|-|-|-|.|}} | |||
{{familytree | E01 | | E02 | | E03 | |E01='''High [[Renin]], High [[aldosterone]]''':• [[Malignant hypertension]]<br>• [[renovascular hypertension]]<br>• [[Renin secretin tumor]]|E02='''Low [[Renin]], High [[aldosterone]]''':• [[Aldosterone secreting tumor]]<br>• [[Adrenal hyperplasia]]<br>• [[Glucocorticoid]] remediable [[aldosteronism]] |E03='''Low [[Renin]], Low [[Aldosterone]]''':• [[Licorice]]<br>• [[Liddle's syndrome]]<br>• [[Enzyme]] deficiency}} | |||
{{familytree/end}} | {{familytree/end}} | ||
== | ==Dos== | ||
*Maintenance of airway, breathing, circulation if there is an unstable patient.<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> | |||
{{ | *Correction of the underlying cause for [[Bicarbonate|HCO3]] production. | ||
*Removal of inciting factors that reabsorb [[Bicarbonate|HCO3]]. | |||
*Patient should be monitored carefully with [[Oxygen saturation|SaO2]], vital signs monitor and [[the electrocardiogram|EKG]]. | |||
*Consider [[Respiratory|respiratory suppor]]<nowiki/>t in hypoxemic patient. | |||
== | ==Don'ts== | ||
== | *Avoid [[hyperventilation]] as it will worsen [[Alkalosis|alkalemia]].<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> | ||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
[[Category:Resident survival guide]] | [[Category:Resident survival guide]] | ||
[[Category: | [[Category:Up-To-Date]] | ||
Latest revision as of 15:32, 2 April 2021
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marufa Marium, M.B.B.S[2]
Synonyms and keywords: Approach to Metabolic alkalosis, Metabolic alkalosis management, Metabolic alkalosis work-up
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 the 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 an increased amount of Bicarbonate(HCO3) in the body or a decreased amount of carbon dioxide or a loss of hydrogen ions, it causes alkalosis. Metabolic alkalosis occurs due to the trapping of Bicarbonate ions (HCO3) or loss of hydrogen ions in the 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 increased 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 the respiratory center to cause hypoventilation, thus decreased PCO2 leading to compensatory respiratory acidosis. The PCO2elevates from 0.5 to 0.7 mmHg per 1.0 mill mole elevation 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.
Causes
Life Threatening Causes
Life-threatening causes of severe metabolic alkalosis (pH 7.55 to 7.65) may result in death (45% to 80%) or permanent disability within 24 hours if left untreated.[1]
Common Causes
- Chloride depletion or Gastrointestinal loss of hydrogen
- GI loss: Vomiting (most commonly seen in pyloric stenosis), NG suction , Zollinger-ellison syndrome, Bulimia.[2]
- Diuretics: Loop and thiazide diuretics.
- Diarrhea: Villous adenoma[3], congenital chloride diarrhea[4]
- Cystic fibrosis.[5]
- Chloride deficient infant formula.
- Gastrocystoplasty [6]
- Post hypercapneic metabolic alkalosis.
- Potassium depletion or Mineralocorticoids excess or Renal loss of hydrogen
- Dietary potassium depletion.[7]
- Primary hyperaldosteronism: Conn syndrome or adenoma, hyperplasia, carcinoma, renin or glucocorticoid responsive.
- Secondary hyperaldosteronism: Reno vascular hypertension, edema (cirrhosis, heart failure, nephrotic syndrome), juxtaglomerular cell(renin producing) tumor, renal cell carcinoma, hemangiopericytoma, nephroblastoma
- Mineralocorticoid excess due to primary decorticosterone excess (11 beta, 17 alpha hydroxylase deficiency), licorice(glycyrrhetinic acid), liddle syndrome.[8] [9]
- Bartter and Gitelman syndrome. [10]
- Laxative
- Reduced Glomerular filtration rate
- ECF volume depletion/ Volume contraction
- Hypovolemia or massive diuresis with loop diuretics.
- Miscellanous
- Hypercalcemia due to Milk-alkali syndrome or bone metastasis.
- Massive blood transfusion.
- Acetate containing colloid sollution.
- Exogenous alkali admintration.
- Combined antacid and cation exchange resin administration.
- Sodium penicillins.
Diagnosis
Shown below is an algorithm summarizing the diagnosis and treatment of Metabolic Alkalosis.[1]
Dos
- Maintenance of airway, breathing, circulation if there is an unstable patient.[10]
- Correction of the underlying cause for HCO3 production.
- Removal of inciting factors that reabsorb HCO3.
- Patient should be monitored carefully with SaO2, vital signs monitor and EKG.
- Consider respiratory support in hypoxemic patient.
Don'ts
- Avoid hyperventilation as it will worsen alkalemia.[10]
References
- ↑ 1.0 1.1 Tripathy S (October 2009). "Extreme metabolic alkalosis in intensive care". Indian J Crit Care Med. 13 (4): 217–20. doi:10.4103/0972-5229.60175. PMC 2856150. PMID 20436691.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Sabatini S (March 1996). "The cellular basis of metabolic alkalosis". Kidney Int. 49 (3): 906–17. doi:10.1038/ki.1996.125. PMID 8648937.
- ↑ 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.
- ↑ 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.
- ↑ 10.0 10.1 10.2 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.