Metabolic alkalosis

Metabolic alkalosis is a disturbance of the acid-base balance characterized by decreased hydrogen and chloride ions in the extracellular fluid, high blood pH, and high blood bicarbonate concentrations. Impaired renal excretion of HCO3~ is required for alkalosis to be maintained. Symptoms and signs in severe cases include headache, lethargy, and tetany. Diagnosis is based on clinical findings and arterial blood gas and plasma electrolyte measurements. Correction of the underlying cause is necessary; intravenous or oral acetazolamide or HCI is sometimes indicated.

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Causes metabolic alkalosis

The main reasons for the development of metabolic alkalosis are the loss of H ⁺ by the body and the load of exogenous bicarbonate.

Losses of H ⁺ by the body with the development of metabolic alkalosis are observed, as a rule, with damage to the gastrointestinal tract and kidney pathology. In these situations, chlorides are lost simultaneously with the loss of hydrogen ions. The body's response aimed at replenishing chloride losses depends on the type of pathology, which is reflected in the classification of metabolic alkalosis.

Loss of H ⁺ through the gastrointestinal tract

This is the most common cause of metabolic alkalosis in internal medicine.

Classification and causes of development of metabolic alkalosis

Classification	Cause
Gastrointestinal tract lesions
Chloride-resistant alkalosis
Chloride-sensitive alkalosis	Vomiting, gastric drainage, vippous adenoma of the rectum or colon
Kidney damage
Chloride-sensitive alkalosis	Diuretic therapy, posthypercapnic alkalosis
Chloride-resistant alkalosis with arterial hypertension	Conn's syndrome, Itsenko-Cushing's syndrome, adrenogenital, renovascular hypertension, drugs with mineralocorticoid properties (carbenoxolone, licorice root), treatment with glucocorticoids
Chloride-resistant alkalosis with normal pressure	Bartter's syndrome, severe potassium depletion
Bicarbonate loading	Massive bicarbonate therapy, massive blood transfusion, treatment with alkaline exchange resins

Gastric juice contains high concentrations of sodium chloride and hydrochloric acid, and lower concentrations of potassium chloride. Secretion of 1 mmol/l H ⁺ into the lumen of the stomach is accompanied by the formation of 1 mmol/l of bicarbonates in the extracellular fluid. Therefore, the loss of hydrogen and chlorine ions during vomiting or suction of gastric juice through a tube is compensated by an increase in the concentration of bicarbonates in the blood. At the same time, potassium is lost, which leads to the release of K ⁺ from the cell with its replacement by H ⁺ ions (development of intracellular acidosis) and stimulation of bicarbonate reabsorption. The developed intracellular acidosis acts as an additional factor contributing to the loss of hydrogen ions due to a compensatory reaction manifested in increased secretion by cells, including the renal tubules, which leads to acidification of the urine. This complex mechanism explains the so-called “paradoxical acid urine” (low urine pH values in conditions of metabolic alkalosis) during prolonged vomiting.

Thus, the development of metabolic alkalosis caused by the loss of gastric juice is due to the accumulation of bicarbonates in the blood in response to several factors: direct loss of H ⁺ with the contents of the stomach, the development of intracellular acidosis in response to hypokalemia, and the loss of hydrogen ions by the kidneys as a compensatory reaction to intracellular acidosis. For this reason, to correct alkalosis, it is necessary to administer solutions of sodium chloride, potassium chloride or HCL.

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Loss of H ⁺ through the kidneys

In this case, alkalosis usually develops with the use of powerful diuretics (thiazide and loop), which remove sodium and potassium in a form bound with chlorine. In this case, a large amount of fluid is lost and hypovolemia develops, a sharp increase in the total excretion of acids and chlorine, resulting in the development of metabolic alkalosis.

At the same time, with prolonged use of diuretics against the background of developed hypovolemia and persistent metabolic alkalosis, compensatory retention of sodium and chlorides occurs, and their excretion with urine decreases to values less than 10 mmol/l. This indicator is important in the differential diagnosis of chloride-sensitive and chloride-resistant variants of metabolic alkalosis. With a chloride concentration of less than 10 mmol/l, alkalosis is assessed as hypovolemic, chloride-sensitive, and it can be corrected by the introduction of sodium chloride solutions.

Symptoms metabolic alkalosis

Symptoms and signs of mild alkalosis are usually related to the etiologic factor. More severe metabolic alkalosis increases protein binding of ionized calcium, leading to hypocalcemia and symptoms of headache, lethargy, and neuromuscular excitability, sometimes with delirium, tetany, and seizures. Alkalemia also lowers the threshold for the onset of symptoms of angina and arrhythmia. Associated hypokalemia may cause weakness.

Forms

Posthypercapnic alkalosis

Posthypercapnic alkalosis usually develops after respiratory failure has been eliminated. The development of posthypercapnic alkalosis is associated with the restoration of the acid-base balance after respiratory acidosis. In the genesis of posthypercapnic alkalosis, the main role is played by increased renal reabsorption of bicarbonates against the background of respiratory acidosis. Rapid restoration of PaCO2 _to normal _with the help of artificial ventilation of the lungs does not reduce the reabsorption of bicarbonates and is replaced by the development of alkalosis. This mechanism of development of acid-base balance disorders requires a careful and slow decrease in _PaCO2 in the blood of patients with chronic hypercapnia.

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Chloride-resistant alkalosis

The main cause of chloride-resistant developmental alkalosis is an excess of mineralocorticoids, which stimulate the reabsorption of potassium and H ⁺ in the distal parts of the nephron and the maximum reabsorption of bicarbonates by the kidneys.

These variants of alkalosis may be accompanied by an increase in blood pressure due to increased primary aldosterone production (Conn's syndrome) or due to activation of the renin RAAS (renovascular hypertension), increased production (or content) of cortisol or its precursors (Itsenko-Cushing's syndrome, treatment with corticosteroids, administration of drugs with mineralocorticoid properties: carbenoxolone, licorice root).

Normal blood pressure is found in diseases such as Bartter syndrome and severe hypokalemia. In Bartter syndrome, hyperaldosteronism also develops in response to activation of the RAAS, but the extremely high production of prostaglandins that occurs in this syndrome prevents the development of arterial hypertension.

The cause of metabolic alkalosis is the disruption of chloride reabsorption in the ascending limb of the loop of Henle, which leads to an increase in the excretion of chlorides in the urine, associated with H ⁺, sodium, and potassium. Chloride-resistant variants of metabolic alkalosis are characterized by a high concentration of chlorides in the urine (more than 20 mmol/l) and resistance of alkalosis to the introduction of chlorides and replenishment of the circulating blood volume.

Another cause of metabolic alkalosis may be bicarbonate overload, which occurs with continuous administration of bicarbonates, massive blood transfusions, and treatment with alkali-exchange resins, when the alkali load exceeds the ability of the kidneys to excrete it.

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Diagnostics metabolic alkalosis

To recognize metabolic alkalosis and the adequacy of respiratory compensation, it is necessary to determine the gas composition of arterial blood and plasma electrolyte levels (including calcium and magnesium).

Often the cause can be determined from the history and physical examination. If the cause is unknown and renal function is normal, urine K and Cl~ concentrations should be measured (values are not diagnostic in renal failure). Urine chloride levels less than 20 mEq/L indicate significant renal reabsorption and suggest a Cl-dependent cause. Urine chloride levels greater than 20 mEq/L suggest a Cl-independent form.

Urinary potassium levels and the presence or absence of hypertension help differentiate Cl-independent metabolic alkalosis.

Urine potassium <30 mEq/day suggests hypokalemia or laxative misuse. Urine potassium >30 mEq/day without hypertension suggests diuretic overuse or Bartter or Gitelman syndrome. Urine potassium >30 mEq/day in the presence of hypertension requires evaluation for hyperaldosteronism, mineralocorticoid excess, or renovascular disease; testing typically includes plasma renin activity and aldosterone and cortisol levels.

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Treatment metabolic alkalosis

Treatment of metabolic alkalosis is closely related to the immediate cause that determines the development of this acid-base imbalance. Treatment of the underlying causes with correction of hypovolemia and hypokalemia is necessary.

Patients with Cl-dependent metabolic alkalosis are given 0.9% saline intravenously; the rate is usually 50-100 mL/hour above urinary and other fluid losses until the urine chloride level is greater than 25 mEq/L and the urine pH has returned to normal after the initial rise due to bicarbonaturia. Patients with O-independent metabolic alkalosis usually do not respond to rehydration.

In patients with severe metabolic alkalosis (e.g., pH > 7.6), more urgent correction of plasma pH is sometimes necessary. Hemofiltration or hemodialysis may be used, especially in hypervolemic patients. Acetazolamide 250-375 mg orally or intravenously once or twice daily increases HCO3- excretion but may also increase urinary K+ or PO4 losses; greatest benefit may be seen in patients with hypervolemia and diuretic-induced metabolic alkalosis or in patients with posthypercapnic metabolic alkalosis.

Intravenous administration of hydrochloric acid in 0.1-0.2 normal solution is safe and effective, but can only be performed through a central catheter due to hyperosmoticity and sclerosis of peripheral veins. The dose is 0.1-0.2 mmol/(kg h) with the need for frequent monitoring of arterial blood gas composition and plasma electrolyte levels.

In case of intensive loss of chlorides and H ⁺ through the gastrointestinal tract, it is necessary to administer chlorine-containing solutions (sodium chloride, potassium chloride, HCl); in case of simultaneous decrease in the volume of circulating blood, its volume must be replenished.

In case of severe hypokalemia against the background of excess mineralocorticoids in the body (Conn's syndrome, Itsenko-Cushing's syndrome, Bartter's syndrome, adrenogenital syndrome), it is necessary to use a low-salt diet, perform surgical treatment of the tumor that caused excess production of mineralocorticoids, use mineralocorticoid antagonists (diuretics: amiloride, triamterene, spironolactone), administer potassium chloride solutions, use indomethacin, and antihypertensive drugs.

In addition, to eliminate metabolic alkalosis in severe hypokalemia that has developed as a result of long-term administration of diuretics, it is necessary to stop their use; with exogenous administration of bicarbonates, stop infusions of alkaline solutions and blood.