Metabolic alkalosis resident survival guide: Difference between revisions
Jump to navigation
Jump to search
(→Don'ts) |
No edit summary |
||
| Line 5: | Line 5: | ||
{{SK}} | {{SK}} | ||
==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 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 | 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.]] | ||
==Causes== | ==Causes== | ||
===Life Threatening 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.<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> | 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> | ||
* [[Loss of gastric acid]] | |||
* [[Loop or thiazide diuretics]] | *[[Gastric acidity reduced|Loss of gastric acid]] | ||
*[[Loop diuretics|Loop]] or [[thiazide diuretics]] | |||
===Common Causes=== | ===Common Causes=== | ||
* '''Chloride depletion''' | |||
**GI loss: Vomiting (most commonly seen in pyloric stenosis), NG suction , Zollinger-ellison syndrome, 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> | *'''[[Chloride]] depletion''' o[[Gastrointestinal|r '''Gastrointestinal''']] '''loss of [[hydrogen]]''' | ||
**Diuretics: Loop and thiazide diuretics. | **[[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]]. | ||
**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> | **[[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> | ||
**Chloride deficient infant formula. | **[[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> | **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. | **Post hypercapneic [[metabolic alkalosis]]. | ||
* '''Potassium depletion''' or ''' | *'''[[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> | **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: Conn syndrome or adenoma, hyperplasia, carcinoma, renin or glucocorticoid responsive. | **[[Primary Hyperaldosteronism|Primary hyperaldosteronism]]: [[Conn syndrome]] or [[adenoma]], [[hyperplasia]], [[carcinoma]], [[renin]] or [[glucocorticoid]] responsive. | ||
**Secondary hyperaldosteronism: Renovascular hypertension, edema (cirrhosis, heart failure, nephrotic syndrome), | **[[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 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> | **[[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 | **[[Laxative]] | ||
*'''Reduced Glomerular filtration rate''' | *'''Reduced [[Glomerular filtration rate]]''' | ||
**Chronic kidney disease | **[[Chronic kidney disease]] | ||
*'''ECF volume depletion/ Volume contraction''' | *'''[[Extracellular fluid|ECF volume]] depletion/ [[Volume depletion|Volume contraction]]''' | ||
**Hypovolemia or massive diuresis with loop diuretics. | **[[Hypovolemia]] or [[Diuresis|massive diuresis]] with [[loop diuretics]]. | ||
*'''Miscellanous''' | *'''Miscellanous''' | ||
**Hypercalcemia due to Milk alkali syndrome or bone metastasis. | **[[Hypercalcemia]] due to [[Milk-alkali syndrome]] or [[bone metastasis]]. | ||
**Massive blood transfusion. | **Massive [[blood transfusion]]. | ||
**Acetate containing colloid sollution. | **[[Acetate]] containing [[Colloid|colloid sollution]]. | ||
**Exogenous alkali admintration. | **[[Exogenous]] [[alkali]] admintration. | ||
**Combined antacid and cation exchange resin adminstration. | **Combined [[antacid]] and cation exchange resin adminstration. | ||
**Sodium penicillins. | **Sodium [[Penicillin|penicillins]]. | ||
==Diagnosis== | ==Diagnosis== | ||
Shown below is an algorithm summarizing the diagnosis and treatment of Metabolic Alkalosis. | Shown below is an [[algorithm]] summarizing the [[diagnosis]] and [[treatment]] of [[Metabolic alkalosis|Metabolic Alkalosis]]. | ||
{{familytree/start |summary=Sample 1}} | {{familytree/start |summary=Sample 1}} | ||
{{familytree | | | | | | | | | | | | A01 | | | | | |A01=History:* H/O Cystic fibrosis/Congenital adrenal hyperplasia/CHF/Uncontrolled HTN? *Excess antacid consumption? * Calcium over supplementation? * Beta lactum use? *Recent or current diuretic use? Vomiting or diarrhea? *massive use of licorice? * H/O recent hypercapneic respiratory failure?}} | {{familytree | | | | | | | | | | | | A01 | | | | | |A01=History:* H/O Cystic fibrosis/Congenital adrenal hyperplasia/CHF/Uncontrolled HTN? *Excess antacid consumption? * Calcium over supplementation? * Beta lactum use? *Recent or current diuretic use? Vomiting or diarrhea? *massive use of licorice? * H/O recent hypercapneic respiratory failure?}} | ||
| Line 64: | Line 66: | ||
==Do's== | ==Do's== | ||
*Maintenance of Airway, breathing, circulation if there is unstable patient. | *Maintenance of Airway, breathing, circulation if there is unstable patient. | ||
*Correction of underlying cause for HCO3 production. | *Correction of underlying cause for HCO3 production. | ||
| Line 71: | Line 74: | ||
==Don'ts== | ==Don'ts== | ||
*Avoid hyperventilation as it will worsen alkalemia. | *Avoid hyperventilation as it will worsen alkalemia. | ||
Revision as of 03:38, 8 December 2020
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahmoud Sakr, M.D. [2]
Synonyms and keywords:
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.
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 adminstration.
- Sodium penicillins.
Diagnosis
Shown below is an algorithm summarizing the diagnosis and treatment of Metabolic Alkalosis.
| History:* H/O Cystic fibrosis/Congenital adrenal hyperplasia/CHF/Uncontrolled HTN? *Excess antacid consumption? * Calcium over supplementation? * Beta lactum use? *Recent or current diuretic use? Vomiting or diarrhea? *massive use of licorice? * H/O recent hypercapneic respiratory failure? | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Physical Examination: *General appearence: Restlessness/ Irritable/lethargic? *Skin: decreased or normal turgor? *HEENT: Headache/Dizziness? *CVS: DYsarrythmia/Tachycardia? * Respiratory: Hypoxemia, Compensatory hypoventilation, Pulmonary microatelactasis, Increased V/Q mismatch *GI: Nausea/vomiting/diarrhea? *GU:Urine output, frequency? *CNS: Confusion, loss of consciousness/Mental obtundation, Neuromuscular excitability/Muscle cramps, Tremor, tingling and numbness in extremities, Weakness? | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laboratory Tests: ABG(pH >7.45, HCO3 >26 mEq/L, PCO2 compensates for increased HCO3 by decreasing), Basic metabolic panel, Serum Aldosterone And renin, Urine analysis, Urine pH, Urine Chloride and sodium, Chest X-ray, Abdominal USG/CT to rule out mass | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Expanded EABV(No sign of volume depletion or Saline unresponsive) *Treatment:Treat underlying cause. | 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. | Rule out by history | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Transient | Renal failure with ingesion | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| *IV HCO3 *Acute correction of hypercapnea | *Milk alkali syndrome *HCO3 ingesion | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| GI loss(low urine Cl) | Renal loss(high urine Cl) | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| *Gastric:Vomiting, NG suction *Lower bowel:Villous adenoma, chloridorrhea, laxative abuse | *Non-reabsorbed ions:Penicillins *Impaired tubular transport:Loop and thiazide diuretics, Barrter's and Gitelman's disease, Hypomagnesemia | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| High Renin, High aldosterone: Malignant hypertension, renovascular hypertension, Renin-secretin tumor | Low Renin, High aldosterone: Aldosterone secreting tumor, Adrenal hyperplasia, Glucocorticoid remediable aldosteronism | Low Renin, Low Aldosterone: Licorice, Liddle's syndrome, Enzyme deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||
Do's
- Maintenance of Airway, breathing, circulation if there is unstable patient.
- Correction of underlying cause for HCO3 production.
- Removal of inciting factors those 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.
References
- ↑ 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.
- ↑ 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.