Metabolic alkalosis 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.

# Historical Perspective
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.

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

# Pathophysiology
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
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.

# Differentiating Xyz from Other Diseases
Metabolic alkalosis might be consequence of several conditions such as exogenous HCO3 loads, medications and poisoning, gastrointestinal, renal, endocrine, and systemic diseases.

# Epidemiology and Demographics
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.

# Risk Factors
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.

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

# Natural History, Complications, and Prognosis
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.

# Diagnosis

## Diagnostic Study of Choice
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.

## History and Symptoms
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.

## Physical Examination
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
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.

## Electrocardiogram
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 .

## X-ray
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.

## Echocardiography and Ultrasound
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.

## CT scan
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.

## MRI
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.

## Other Imaging Findings
There are no other imaging findings associated with Metabolic alkalosis.

## Other Diagnostic Studies
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.

# Treatment

## Medical Therapy
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.

## Surgery
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.

## Primary Prevention
There are no available vaccines against Metabolic alkalosis.

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