Metabolic alkalosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marufa Marium, M.B.B.S[2]

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.

Alkalosis is defined as elevation of physiologic blood pH above 7.45. Metabolic alkalosis is caused by metabolic imbalance causing alkalosis by trapping Bicarbonate ions or loss of hydrogen in body. The discovery of electrochemistry of gas and electricity was first explored in 17th and 18th centuries . Later in late 1880s definition of acid was first developed and modified by numerous scientists from 1880s to 1950s until the epidemic era of Polio. Stewart combined all the ideas from pre-1950 and proposed a way of studying acid-base balance in clinical settings.

Metabolic Alkalosis can be classified according to pathophysiology, etiology and chloride responsiveness or urinary chloride concentration.

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 elevates from 0.5 to 0.7 mmHg per 1.0 millimole 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 of Metabolic Alkalosis are Vomiting, Diarrhea, Diuretics, Cystic Fibrosis, Primary Hyperaldosteronism, Secondary hyperaldosteronism, laxative use, CKD, elactrolyte and nutritional imbalances, Milk-alkali syndrome, Blood transfusion, Genetic diseases for instances Bartter, Liddle, Gitelman syndrome etc. Among them, life threatening causes are loss of gastric acid, excessive use of loop and thiazide diuretics.

Metabolic alkalosis might be consequence of several conditions such as exogenous HCO3− loads, medications and poisoning, gastrointestinal, renal, endocrine, and systemic diseases.

Metabolic Alkalosis has the highest incidence and prevalence rate among the other acid base disorder in hospitalized patient. Limited data are found on its predilection to race, age, gender, region.

Common risk factors in the development of Metabolic Alkalosis include Vomiting, Milk-alkali syndrome, Severe hypokalemia, Primary hyperaldosterinism, Cushing syndrome, Diuretics use and genetic disease for instances- Bartter and gitelman Disease.

There is insufficient evidence to recommend routine screening for Metabolic alkalosis.

Common complications of Metabolic alkalosis include hypokalemia, hypomagnesaemia, hypophosphatemia, coronary arterial blood flow reduction, arrhythmia, anaerobic glycolysis, reduced ventilation leading to low arterial oxygen saturation, increased CO2, decreased blood flow to cerebral arteries leading to altered mental status, lethargy, tetany, delirium, seizure.

Arterial Blood Gas Analysis(ABG) is gold standard for diagnosis of Metabolic Alkalosis. Other laboratory tests, for instance Basic metabolic panel, serum aldosterone, serum renin, Urine analysis, urine pH, Urine chloride and sodium, Chest X-ray, Abdominal USG/CT are done to rule out the causes of metabolic alkalosis.

The hallmark of Metabolic Alkalosis is elevated HCO3 ion in serum primarily. A positive history of cystic fibrosis, Congenital Adrenal Hyperplasia, CHF, Uncontrolled HTN, Excess Antacid consumption, Calcium over supplementation, Penicillin use, Recent diuretics use, Vomiting, Diarrhea, Licorice consumption, Massive Blood transfusion are suggestive of Metabolic Alkalosis. The most common symptoms of Metabolic Alkalosis include nausea, vomiting, diarrhea, irritability, restlessness. Common symptoms of metabolic alkalosis include muscle cramp, tingling, tremor, slow respiration. Less common symptoms of metabolic alkalosis include loss of consciousness, altered mental status etc.

Patients suffering from Metabolic alkalosis usually appear restless, irritable. Patients with metabolic alkalosis is usually remarkable for tachycardia/dysrhythmia, hypoxemia, Hypoxemia, Compensatory hypoventilation, Muscle cramps, Tremor, tingling and numbness in extremities, Weakness on clinical examination.

Laboratory findings consistent with the diagnosis of Metabolic Alkalosis include ABG (pH >7.45, HCO3 >26 mEq/L, PCO2 compensates for increased HCO3 by decreasing.), high or low Serum aldosterone/Serum renin, and Urine analysis with Urine pH and high or low Urine chloride and sodium.

An ECG may be helpful in the diagnosis of Hypokalemia, an etiology of metabolic alkalosis. Findings on an ECG diagnostic of Hypokalemia include Depression in ST segment with decreased T wave and , prominent U wave, and prolonged PR interval with widened QRS .

There are no x-ray findings associated with Metabolic alkalosis. However, an x-ray may be helpful in the diagnosis of etiology of metabolic alkalosis, which include Cystic Fibrosis, Heart failure, Nephroblastoma, NG Suction.

There are no echocardiography/ultrasound findings associated with Metabolic alkalosis. However, an echocardiography/ultrasound may be helpful in the diagnosis of etiology of Metabolic Alkalosis, which include Heart failure, Cirrhosis, Cystic fibrosis, Pyloric stenosis, Adrenal adenoma, renal cell carcinoma, Renin producing tumor, Gastrocystoplasty and nephroblastoma.

There are no CT scan findings associated with Metabolic alkalosis. However, an echocardiography/ultrasound may be helpful in the diagnosis of etiology of Metabolic Alkalosis, which include Heart failure, Cirrhosis, Cystic fibrosis, Pyloric stenosis, Adrenal adenoma, renal cell carcinoma, Renin producin tumor, Gastrocystoplasty and nephroblastoma.

There are no MRI findings associated with Metabolic alkalosis. However, an echocardiography/ultrasound may be helpful in the diagnosis of etiology of Metabolic Alkalosis, which include Heart failure, Cirrhosis, Cystic fibrosis, Pyloric stenosis, Adrenal adenoma, renal cell carcinoma, Renin producin tumor, Gastrocystoplasty and nephroblastoma.

There are no other imaging findings associated with Metabolic alkalosis.

Genetic testing for identifying genes involved in the pathogenesis of Metabolic Alkalosis include CFTR, SCNN1A/SCNN1B/SCNN1G, NKCC2;, SLC12A3/CLCNKB, SLC26A3 causing Cystic Fibrosis, Liddle Syndrome, Bartter syndrome, Gitelman syndrome and Congenital Chloride Diarrhhea respectively.

Supportive therapy for Metabolic alkalosis includes volume repletion, electrolyte repletion, removal of inducing source and after stabilizing patient treatment according to etiology. Pharmacologic medical therapy is recommended among patients with electrolyte imbalances, hypervolemia, loss of GI hydrogen.

The mainstay of treatment for metabolic alkalosis is medical therapy. Surgery is usually reserved for patients with either pyloric stenosis), Zollinger- Ellison syndrome, Villous adenoma, Conn syndrome or adrenal adenoma/ hyperplasia /carcinoma, Reno vascular hypertension, juxtaglomerular cell(renin producing) tumor, renal cell carcinoma, hemangiopericytoma, nephroblastoma.

There are no available vaccines against Metabolic alkalosis.

Effective measures for the secondary prevention of metabolic alkalosis include resuscitation with airway, breathing, circulation, correction of electrolyte imbalance, and removal of inciting sources.

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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]

Alkalosis is defined as elevation of physiologic blood pH above 7.45. Metabolic alkalosis is caused by metabolic imbalance causing alkalosis by trapping Bicarbonate ions or loss of hydrogen in body. The discovery of electrochemistry of gas and electricity was first explored in 17th and 18th centuries . Later in late 1880s definition of acid was first developed and modified by numerous scientists from 1880s to 1950s until the epidemic era of Polio. Stewart combined all the ideas from pre-1950 and proposed a way of studying acid-base balance in clinical settings.

In the beginning era of exploration of acid-base physiology, there are contribution of many scientists from 1880s to modern time. In 1880s Arrhenius defined acid for the first time as a substance which helped in increasing hydrogen ions concentration when dissolving with water. Naunyn combined definitions from Arrhenius and Faraday and came up with ideas of electrolytes determining acid-base physiology.^[1] Van Slyke modified the definition of acid by Naunyn in 1920. Bronsted and Lowry defined acid as a substance donating hydrogen ion just after World War One, whereas Lewis suggested acid as acceptor of electron pair. Henderson and Hasselbalch contributed in development of Henderson-Hasselbalch equation linking pH, PCO2, HCO3 concentration in 1908 and 1916 respectively. The role of HCO3 in acid-base physiology first came up in 1950s.^[2][3]

A group of physicians from Denmark erroneously discovered metabolic alkalosis by using bicarbonate concentration in plasma during the emergence of polio epidemic in 1952.^[4]

The Polio epidemic triggered the development of glass electrode and detection of pH by Astrup in blood. He worked with Siggard-Anderson to build the foundation od clinical acid-base balance.^[5]

From 1970 to 1980s Stewart showed detailed integration of clinical acid-base physiology and applied HCO3 centered in clinical settings.^[6]

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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]

Metabolic Alkalosis can be classified according to pathophysiology, etiology and chloride responsiveness or urinary chloride concentration.

• 1.The following classification of Metabolic Alkalosis is based on Pathophysiology^[1]:

Metabolic Alkalosis

Stimulation on Collecting Duct

Primary stimulation by Mineralocorticoid Excess causing HTN: •Congenital Adrenal Hyperplasia •Cushing Syndrome •Primary aldosteronism •Renin Secreting tumors •Medications(Fluoroprednisolone, Fludrocortisone) •Liddle Syndrome •11 beta hydroxysteroid dehydrogenase deficiency

Secondary Stimulation by Chloride depletion causing normal or low blood pressure: •Vomiting •NG tube intubation •Congenital Chloridorrhea •Ileostomy •Cystic fibrosis •Diuretics •Bartter syndrome •Gitelman syndrome •Hypokalemia

• 2.The classification based on etiologies are following:

• 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
  • Chronic kidney disease
• 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.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marufa Marium, M.B.B.S[2]

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 elavates from 0.5 to 0.7 mmHg per 1.0 millimole 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. Supportive Treatment is usually given according to cause of the disease.

• • [[Emesis] (most commonly seen in pyloric stenosis), NG suction , Zollinger-ellison syndrome, Bulimia.^[1]
  • Diuretics: Loop and thiazide diuretics.
  • Diarrhea: Villous adenoma^[2], congenital chloride diarrhea^[3]
  • Cystic fibrosis.^[4]
  • Chloride deficient infant formula.
  • Gastrocystoplasty ^[5]
  • Post hypercapneic metabolic alkalosis.

• • Dietary potassium depletion.^[6]
  • 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.^{[7] [8]}
  • Bartter and Gitelman syndrome. ^[9]

• Intake of NaCO3, citrate, baking powder, lactate and acetate.

• Occurs in hypokalemia. Decreased extracellular K+, potassium transports from the cells, and to keep electrical potential in a balanced state, Transport of H+ to IC space.

• Loss of low concerntation of HCO3 mixed H2O in EC space by diuretics. HCO3 is elevated in serum..

• hypoventilation (respiratory compensation) elevates pH by restoring carbon dioxide (CO₂) through . Carbonic acid is generated by CO₂. The acidic medium is created for compensation.
• The pCO2 elevates from 0.5 to 1 per 1 u serum HCO3 elevation.
• Body can compensate up tp 55-60 mmHg of partial pressure of CO2.
• Increased secretion of HCO₃^– (bicarbonate) by kidney is done.

• Genes involved in the pathogenesis of Metabolic Alkalosis include CFTR, SCNN1A/SCNN1B/SCNN1G^[10], NKCC2^[11] SLC12A3/CLCNKB^[12] and SLC26A3 ^[13] causing Cystic Fibrosis, Liddle Syndrome, Bartter syndrome, Gitelman syndrome and Congenital Chloride Diarrhhea respectively.

Conditions associated with metabolic alkalosis :

• • Vomiting (most commonly seen in pyloric stenosis
  • NG suction
  • Zollinger-ellison syndrome
  • Bulimia.^[1]
  • Diuretics: Loop and thiazide diuretics.
  • Villous adenoma^[2]
  • congenital chloride diarrhea^[3]
  • Cystic fibrosis^[4]
  • Chloride deficient infant formula.
  • Gastrocystoplasty ^[5]
  • Post hypercapneic metabolic alkalosis.
  • Dietary potassium depletion.^[6]
  • 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.^{[7] [8]}
  • Bartter and Gitelman syndrome. ^[9]
  • Laxative
  • Chronic kidney disease
  • Hypovolemia or massive diuresis with loop diuretics.
  • 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.

• • There is no specific gross pathological finding related to metabolic alkalosis. Gross characteristics are dependent on specific cause of metabolic alkalosis.

• • There is no specific microscopic pathological finding related to metabolic alkalosis. Gross characteristics are dependent on specific cause of metabolic alkalosis.

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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]

Causes of Metabolic Alkalosis are Vomiting, Diarrhea, Diuretics, Cystic Fibrosis, Primary Hyperaldosteronism, Secondary hyperaldosteronism, laxative use, CKD, elactrolyte and nutritional imbalances, Milk-alkali syndrome, Blood transfusion, Genetic diseases for instances Bartter, Liddle, Gitelman syndrome etc. Among them, life threatening causes are loss of gastric acid, excessive use of loop and thiazide diuretics.

There are several causes of metabolic alkalosis. 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]

• Loss of gastric acid
• Loop or thiazide diuretics

• 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
  • Cystic fibrosis.^[3]
  • Chloride deficient infant formula.
• Potassium depletion or Mineralocorticoids excess or Renal loss of hydrogen
  • Dietary potassium depletion.^[4]
  • 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, nephroblastoma
  • Mineralocorticoid excess due to primary decorticosterone excess (11 beta, 17 alpha hydroxylase deficiency), licorice(glycyrrhetinic acid) Closing </ref> missing for <ref> tag
  • congenital chloride diarrhea^[5]
  • Bartter and Gitelman syndrome. ^[6]
  • liddle syndrome</ref> ^[7]
  • hemangiopericytoma
  • Gastrocystoplasty ^[8]
  • Post hypercapneic metabolic alkalosis.

Cardiovascular	Dilated cardiomyopathy, Malignant hypertension, Renovascular hypertension
Chemical / poisoning	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	Aldosterone, Carbenoxolone, Diuretics, Ethacrynic Acid, Fludrocortisone, Glucocorticoids, Intravenous Pencillins, Laxatives, Lydia Pinkham’s vegetable compound, Mineralocorticoids, Pramipexole, Sodium bicarbonate, Tolazoline, Tromethamine
Ear Nose Throat	No underlying causes
Endocrine	Cushing syndrome, Glucocorticoid-remediable hyperaldosteronism, Hyperaldosteronism, 11 beta hydroxylase deficiency, C17-hydroxylase deficiency, Conn syndrome, Bilateral adrenal hyperplasia, Adrenal adenoma, Adrenal carcinoma
Environmental	No underlying causes
Gastroenterologic	Gastric fistula, Villous adenoma, VIPoma, Congenital chloride diarrhea, Cystic fibrosis
Genetic	11 beta hydroxylase deficiency, Bartter syndrome, C17-hydroxylase deficiency, Congenital chloride diarrhea, Cystic fibrosis, Gietelman syndrome, Glucocorticoid receptor defect, Liddle syndrome, SeSAME syndrome
Hematologic	No underlying causes
Iatrogenic	Massive blood transfusion, Nasogastric suction
Infectious Disease	No underlying causes
Musculoskeletal / Ortho	No underlying causes
Neurologic	No underlying causes
Nutritional / Metabolic	Hypercalcemia, Hypokalemia, Hypomagnesemia, Refeeding syndrome, Glucocorticoid receptor defect, Glycyrrhizic acid, Licorice
Obstetric/Gynecologic	No underlying causes
Oncologic	Adrenal adenoma, Adrenal carcinoma, Conn syndrome, Hemangiopericytoma,VIPoma, Juxtaglomerular cell tumor
Opthalmologic	No underlying causes
Overdose / Toxicity	Aldosterone, Carbenoxolone, Diuretics, Fludrocortisone, Glucocorticoids, Intravenous Pencillins, Laxatives, Lydia Pinkham’s vegetable compound, Mineralocorticoids, Sodium bicarbonate, Tolazoline, Tromethamine
Psychiatric	No underlying causes
Pulmonary	Cystic fibrosis
Renal / Electrolyte	Bilateral adrenal hyperplasia, Hypokalemic distal renal tubular acidosis, Juxtaglomerular cell tumor, Milk-alkali syndrome, Renovascular hypertension, Bartter syndrome, Gietelman syndrome, Liddle syndrome, Adrenal adenoma, Adrenal carcinoma
Rheum / Immune / Allergy	No underlying causes
Sexual	Cystic fibrosis
Trauma	No underlying causes
Urologic	No underlying causes
Dental	No underlying causes
Miscellaneous	Chewing tobacco, Glycyrrhizic acid, Licorice, Posthypercapnia, Vomiting, Laxatives, Refeeding syndrome, Milk-alkali syndrome

11 beta hydroxylase deficiency Adrenal adenoma Adrenal carcinoma Aldosterone Bartter syndrome Bilateral adrenal hyperplasia C17-hydroxylase deficiency Carbenoxolone Chewing tobacco Congenital chloride diarrhea Conn syndrome Cushing syndrome Cystic fibrosis Dilated cardiomyopathy Diuretics Fludrocortisone Gastric fistula Gietelman syndrome Glucocorticoid receptor defect Glucocorticoid-remediable hyperaldosteronism Glucocorticoids Glycyrrhizic acid Hemangiopericytoma Hyperaldosteronism Hypercalcemia

Hypokalemia Hypokalemic distal renal tubular acidosis Hypomagnesemia Intravenous Pencillins Juxtaglomerular cell tumor Laxatives Licorice Liddle syndrome Lydia Pinkham’s vegetable compound Malignant hypertension Massive blood transfusion Milk-alkali syndrome Mineralocorticoids Nasogastric suction Posthypercapnia Refeeding syndrome Renovascular hypertension SeSAME syndrome Sodium bicarbonate Tolazoline Tromethamine Villous adenoma VIPoma Vomiting

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2]

Metabolic alkalosis might be consequence of several conditions such as exogenous HCO₃⁻ loads, medications and poisoning, gastrointestinal, renal, endocrine, and systemic diseases.

Differential diagnosis of metabolic alkalosis is as follow:

Category	Disease		Mechanism				Clinical						Paraclinical												Gold standard diagnosis	Other findings
							Symptoms			Signs			Lab data
													ABG			Chemistry					Enzyme	Renal function
			Hydrogen loss	Accumulation of base	Chloride depletion	Mineralocorticoid excess	Fever	Dyspnea	Edema	Toxic/ill	BP	Dehydration	HCO3−	paCO2	O2	Cl−	K+	Na+	Ca+	Mg+	Renin	Bun	Cr	Urine Cl−
Exogenous HCO3− loads	Acute alkali administration[1]		−	+	−	−	−	+	−	+	↓	−	↑	↑	↓	↓	↓	↓	↑	Nl	Nl	↑	↑	Nl	Clinical manifestations	Post treatment of lactic acidosis or ketoacidosis Increased risk of renal stones
	Milk−alkali syndrome[2]		−	+	−	+	−	+	−	+	↓	+	↑	↑	↓	↓	↓	↓	↑	↓	↑	↑	↑	Nl	Clinical manifestationsk + exclusion of other causes of hypercalcemia	Ingestion of large amounts of calcium and absorbable alkali Acute kidney injury
	Transfusion[3]		−	+	−	−	±	±	−	+	↓	−	↑	↑	↓	↓	↓/↑	↓	↓	↑	↑	Nl to ↑	Nl to ↑	Nl	History of administration of large quantities of blood products that contain sodium citrate	Associated with renal impairment
Drugs/Medication	Chloruretic diuretics[4]	Bumetanide Chlorothiazide Metolazone	+	−	+	+	−	−	−	−	↓	+	↑	↑	Nl	↓	↓	↑	Nl	Nl	↑	Nl to ↑	Nl to ↑	↑	History of diuretic use	Contraction alkalosis
	Penicillin[5]		+	−	−	−	−	−	−	−	Nl	−	↑	↑	Nl	↓	↓	↑	Nl	↓	↑	Nl	Nl	Nl	History of penicillin use	Not applicable
	Licorice[6][7]		+	−	−	+	−	−	−	+	Nl to ↑	−	↑	↑	Nl	↓	↓	↑	Nl	Nl	↑	Nl to ↑	Nl to ↑	Nl	Clinical manifestations	Muscle weakness Paralysis
	Laxative abuse[8]		+	−	+	−	−	−	±	+	↓	+	↑	↑	Nl	↓	↓	↑	Nl	↑	↑	Nl to ↑	Nl	↓	High level of suspicion	Large−volume, watery diarrhea Cramping abdominal pain Weight loss
	Antacids[9][10]	Aluminum hydroxide Sodium polystyrene sulfonate	+	+	−	−	−	−	−	−	Nl	−	↑	↑	Nl	↓	↓	↑	Nl	↑	Nl	Nl to ↑	Nl to ↑	Nl	Clinical manifestations	Not applicable
Category	Disease		Hydrogen loss	Accumulation of base	Chloride depletion	Mineralocorticoid excess	Fever	Dyspnea	Edema	Toxic/ill	BP	Dehydration	HCO3−	paCO2	O2	Cl−	K+	Na+	Ca+	Mg+	Renin	Bun	Cr	Urine Cl−	Gold standard diagnosis	Other findings
Gastrointestinal origin	Vomiting[11]		+	−	+	−	±	−	−	+	↓	+	↑	↑	Nl	↓	↓	↑	Nl	Nl	↑	Nl to ↑	Nl	↓	Clinical manifestations	Not applicable
	Nasogastric tube suction[12]		+	−	+	−	−	−	−	+	↓	+	↑	↑	Nl	↓	↓	↑	Nl	Nl	↑	Nl to ↑	Nl	↓	Clinical manifestations	GERD Pulmonary aspiration
	Zollinger−Ellison syndrome[13]		+	−	+	−	−	−	−	+	↓	+	↑	↑	Nl	↓	↓	↑	Nl	Nl	↑	Nl to ↑	Nl	↓	Serum gastrin concentration + secretin stimulation test	Multiple or refractory peptic ulcers Chronic diarrhea MEN1
	Bulimia nervosa[14]		+	−	+	−	−	−	±	+	↓	+	↑	↑	Nl	↓	↓	↓	Nl	↓	↑	Nl to ↑	Nl	↓	High level of suspicion	Lethargy Irregular menses Abdominal pain Constipation Salivary gland hypertrophy
	Congenital chloridorrhea[15]		+	−	+	−	−	−	±	+	↓	+	↑	↑	Nl	↓	↓	↓	↓	↓	↑	Nl to ↑	Nl to ↑	Nl to ↑	Clinical manifestations+ lab findings	Profuse diarrhea Polyhydramnios
	Pyloric stenosis[16]		+	−	+	−	−	−	−	+	↓	+	↑	↑	Nl	↓	↓	↓ ↑	Nl	Nl	↑	Nl to ↑	Nl	↓	Physical exam + imaging	Palpation of the “olive”
	Villous adenoma[17]		+	−	+	−	−	−	−	+	↓	+	↑	↑	Nl	↓	↓	↓	↓	↓	↑	Nl to ↑	Nl	↑	Colonoscopy	Metabolic acidosis
	Gastrocystoplasty[18]		−	−	+	−	−	−	+	−	↓	−	↑	↑	Nl	↓	Nl	Nl	Nl	Nl	Nl	Nl to ↑	Nl to ↑	Nl	History of operation	Hematuria−dysuria syndrome
Category	Disease		Hydrogen loss	Accumulation of base	Chloride depletion	Mineralocorticoid excess	Fever	Dyspnea	Edema	Toxic/ill	BP	Dehydration	HCO3−	paCO2	O2	Cl−	K+	Na+	Ca+	Mg+	Renin	Bun	Cr	Urine Cl−	Gold standard diagnosis	Other findings
Renal origin	Posthypercapnic state[19]		−	−	+	+	−	±	−	−	Nl	−	↑	↑↑	↓	↓	↓	↑	Nl	Nl	↑	Nl	Nl	Nl	Lab findings	Chronic respiratory acidosis
	Hypomagnesemia[20]		+	−	−	−	−	−	−	−	Nl	−	↑	↑	Nl	↓	↓	↑	Nl	Nl	↑	Nl	Nl	Nl	Lab findings	Not applicable
	Hypokalemia[21]		+	−	−	−	−	−	−	−	Nl	−	↑	↑	Nl	↓	↓	↑	Nl	Nl	↑	Nl	Nl	Nl	Lab findings	Not applicable
	Bartter’s syndrome[22]		+	−	−	+	−	−	−	−	Nl	+	↑	↑	Nl	↓	↓↓	↓	↓	Nl	↑	Nl to ↑	Nl to ↑	Nl	Genetic testing	Constipation Muscle cramps and weakness Failure to thrive Sensorineural deafness Focal segmental glomerulosclerosis Hypercalciuria
	Gitelman’s syndrome[23][24]		+	−	−	+	−	−	−	−	↓	+	↑	↑	Nl	↓	↓↓	↓	Nl	↓	↑	Nl	Nl	Nl	Genetic testing	Less severe Constipation Muscle cramps and weakness Hypocalciuria
	Renal artery stenosis[25]		+	−	+	−	−	+	+	+	↑	+	↑	↑	↓	↓	↑	↓	↑	Nl	↑	↑	↑	Nl	Clinical manifestations+ imaging	Chronic kidney disease Acute rise in Cr following ACEIs or ARBs
	Liddle syndrome[26]		+	−	−	+	−	−	−	−	↑	+	↑	↑	Nl	↓	↓↓	↓	Nl	↓	↑	Nl	Nl	Nl	Genetic testing	Not applicable
	Renal tumors[27]		+	−	+	−	−	+	+	+	↑	+	↑	↑	↓	↓	↑	↓	↑	Nl	↑	↑	↑	Nl	Biopsy	Not applicable
Endocrine	Cushing’s syndrome[28]		+	−	+	−	−	−	+	−	↑	+	↑	↑	Nl	↓	↑	↓	↑	Nl	↓	↑	↑	Nl	24−hour urinary cortisol excretion + low−dose dexamethasone suppression test	Obesity Lethargy Hirsutism Menstrual changes
	Hyperaldosteronism	Primary[29]	+	−	+	−	−	−	+	−	↑	+	↑	↑	Nl	↓	Nl to ↓	↓	↑	Nl	↓	↑	↑	Nl	Lab findings	Resistant HTN Aldosterone−producing adenomas Bilateral adrenal hyperplasia
		Secondary[30]	+	−	+	−	−	+	+	+	↑	+	↑	↑	Nl	↓	↓	↑	Nl	↓	↑	↑	↑	Nl	Lab findings	Renin−producing tumor Renal artery stenosis Left ventricular heart failure Cor pulmonale Cirrhosis with ascites
	Congenital adrenal hyperplasia	11β−Hydroxylase deficiency[31]	−	−	−	+	−	−	+	−	↑	+	↑	↑	Nl	↓	↓	↓	↑	Nl	↓	Nl	Nl	Nl	Genetic testing	Virilization Skin hyperpigmentation Bilateral adrenal gland enlargement
		17α−Hydroxylase deficiency[32]	−	−	−	+	−	−	+	−	↑	+	↑	↑	Nl	↓	↓	↓	↑	Nl	↓	Nl	Nl	Nl	Genetic testing	Ambiguous genitalia Undescended testes Lacks 2° sexual development Skin hyperpigmentation Bilateral adrenal gland enlargement
Systemic	Cystic fibrosis[33]		+	−	+	−	−	+	−	+	↓	+	↑	↑	Nl	↓	↓	Nl	Nl	Nl	↑	Nl to ↑	Nl	↑	Genetic testing	Fatigue Persistent pulmonary infection Pancreatic insufficiency
Category	Disease		Hydrogen loss	Accumulation of base	Chloride depletion	Mineralocorticoid excess	Fever	Dyspnea	Edema	Toxic/ill	BP	Dehydration	HCO3−	paCO2	O2	Cl−	K+	Na+	Ca+	Mg+	Renin	Bun	Cr	Urine Cl−	Gold standard diagnosis	Other findings

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Metabolic Alkalosis has the highest incidence and prevalence rate among the other acid base disorder in hospitalized patient. Limited data are found on its predilection to race, age, gender, region.

• The incidence of metabolic alkalosis is highest among all other acid based disorders. The incidence of metabolic alkalosis is approximately 51% in hospitalized patient.^[1]

• Metabolic Alkalosis is shown to occur in 70% of 13430 cases in a study.^[2]

• 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.

• Patients of all age groups may develop Metabolic Alkalosis.

• There is no racial predilection to Metabolic alkalosis.

• Metabolic Alkalosis affects men and women equally.

• There is no regional predilection for Metabolic Alkalosis.

• There is no sufficient data specifically mentioning population from developed countries.

• There is no sufficient data specifically mentioning population from developing countries.

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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]

Common risk factors in the development of Metabolic Alkalosis include Vomiting, Milk-alkali syndrome, Severe hypokalemia, Primary hyperaldosterinism, Cushing syndrome, Diuretics use and genetic disease for instances- Bartter and gitelman Disease.

• Common risk factors in the development of Metabolic Alkalosis include Vomiting, Milk-alkali syndrome, Severe hypokalemia, Primary hyperaldosterinism, Cushing syndrome, Diuretics use and genetic disease for instances- Bartter and Gitelman Disease.

• Common risk factors in the development of Metabolic Alkalosis in patients who have conditions include:
  • Vomiting (most commonly seen in pyloric stenosis), NG suction
  • Diuretics: Loop and thiazide diuretics.
  • Diarrhea
  • Cystic fibrosis.^[1]
  • Dietary potassium depletion.^[2]
  • 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, nephroblastoma
  • Mineralocorticoid excess due to primary decorticosterone excess (11 beta, 17 alpha hydroxylase deficiency), licorice(glycyrrhetinic acid) Closing </ref> missing for <ref> tag
  • Chloride deficient infant formula.
  • Villous adenoma^[3]
  • congenital chloride diarrhea^[4]
  • Bartter and Gitelman syndrome. ^[5]
  • liddle syndrome</ref> ^[6]
  • hemangiopericytoma
  • Gastrocystoplasty ^[7]
  • Post hypercapneic metabolic alkalosis.

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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]

There is insufficient evidence to recommend routine screening for Metabolic alkalosis.

There is insufficient evidence to recommend routine screening for Metabolic alkalosis. But there are certain etiologies of metabolic alkalosis should be screened for early diagnosis.

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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]

Common complications of Metabolic alkalosis include hypokalemia, hypomagnesaemia, hypophosphatemia, coronary arterial blood flow reduction, arrhythmia, anaerobic glycolysis, reduced ventilation leading to low arterial oxygen saturation, increased CO2, decreased blood flow to cerebral arteries leading to altered mental status, lethargy, tetany, delirium, seizure.

• The mortality rate with metabolic alkalosis is 45% with arterial blood pH 7.55 to 80% with arterial blood pH of 7.65.

• Common complications of Metabolic alkalosis include:
  • Electrolyte imbalances: hypokalemia, hypomagnesaemia, hypophosphatemia
  • Coronary arterial blood flow reduction leading to angina, refractory arrhythmia
  • Anaerobic glycolysis
  • Reduced ventilation leading to low arterial oxygen saturation, increased CO2
  • Decreased blood flow to cerebral arteries leading to altered mental status, lethargy, tetany, delirium, seizure. .

• Early stabilization of patient is associated with the most favorable prognosis.

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