Metabolic Alkalosis

Metabolic alkalosis is a condition of high blood pH (pH>7.45) due to excess bicarbonate in the body and/or a loss of acid (H+).

Metabolic Alkalosis Causes

Metabolic Alkalosis is caused either by an increase of bicarbonate (HCO₃^–) or a loss of protons (i.e. acid) leading to HCO^– retention. Regardless of initial cause, persistence of metabolic alkalosis indicates that the kidneys have increased their HCO₃^– reabsorption, because HCO₃− is normally freely filtered by the kidneys and hence excreted. Stomach acid depletion and hypokalemia are the most common stimuli for increased HCO₃^– reabsorption, but any condition that elevates aldosterone or mineralocorticoids (which enhance sodium [Na⁺] reabsorption and potassium [K⁺] and hydrogen ion [H⁺] excretion) can elevate HCO₃^–. Thus, hypokalemia is both a cause and a frequent consequence of metabolic alkalosis.

Excessive HCO₃^– Administration

Excessive HCO₃^– can occur by ingesting excessive amounts of base: antacids for GI upset, being a typical example. However, HCO₃^– administration can also occur during blood transfusion where blood plasma is suddenly introduced. You may recall that plasma is rich in HCO₃^– and that a whole blood/plasma transfusion is, in essence, a HCO₃^– infusion.

Gastric Loss of H⁺ (Stomach Acid)

The generation of stomach acid requires the use of many protons. When a patient is continuously vomiting or losing stomach acid from continuous nasogastric suction, they are shedding protons through the loss of stomach acid. When the serum proton level drops, there is more free bicarbonate throwing the patient into an alkalotic state. ^[2]

Extracellular fluid Loss of H⁺: Hypokalemia

When a patient has a low extracellular potassium level, protons migrate out of the intracellular space to maintain the gradient across the membrane, in order to maintain electroneutrality against other anions. As a result, H⁺ migrates INTO the intracellular space making the blood less acidic, thus driving a metabolic alkalosis. ^[5]

Renal Loss of H⁺: Loop Diuretics

When a patient takes a loop diuretic, the the Na+/K+/2Cl− cotransporter is blocked leading to leakage of Na+, K+ & Cl- and water into the filtrate. The loss of K+ can lead to hypokalemia which, as just mentioned, can lead to H+ being shifted intracellularly.  The loss of Cl- will promote HCO3- retention leading to potentially alkalosis.  In addition, diuretics will cause volume depletion and thus activation of RAAS.  Aldosterone secretion will promote Na+ reabsorption and hence, increases action of the sodium-hydrogen antiporter. This will transfer more H+ into the urine, thus a loss of acid in the body.  This puts the patient at further risk for metabolic alkalosis.^[4] For a quick review on kidney physiology, please see Physiology of urine formation.

Renal Loss of H⁺ and Retention of HCO₃^–: Hyperaldosteronism

Excess aldosterone will lead to increased sodium absorption in the collecting ducts resulting in the excretion of hydrogen and potassium. This increased proton clearance leads to retention of more bicarbonate.^[4] Potassium loss can worsen metabolic alkalosis because the body will adjust to this potassium lost by shifting intracellular K⁺ to the extracellular space, resulting in H⁺ shifting into the intracellular space, in exchange. This will cause the pH to increase in the extracellular fluid.

Compensation to Metabolic Alkalosis

The body detects pH through chemoreceptors in the aorta, carotid, glossopharyngeal and vagus nerve. In response, both the lungs and kidneys can compensate for metabolic alkalosis:

Respiratory compensation: If pH is alkalotic, a signal is sent to the respiratory centres in the brain and breathing is slowed in order to retain carbonic acid in the blood (i.e. less CO₂ is exhaled and can be converted to carbonic acid, thus lowering pH).

Renal compensation: Assuming that the cause of the metabolic alkalosis is not from renal causes, the kidneys will try to compensate by filtering more bicarbonate for excretion.

Complications

In the kidneys potassium is reabsorbed by the potassium proton exchanger. Protons are brought into the urine filtrate and potassium is reabsorbed. When the proton concentration drops, it slows the action of the potassium proton exchanger, leading to excessive potassium excretion, which in turn causes hypokalemia in the patient. Thus, hypokalemia can be both a cause and a complication of metabolic alkalosis.

Hypokalemia is a dangerous electrolyte disturbance as K⁺ is so important for electrical activity. Thus, disturbances in electrical conduction in the heart (arrhythmias), muscles (weakness), and nervous system (altered mental status) can manifest.

Clinical Manifestations

The clinical manifestation of metabolic alkalosis is highly variable, as many pathologies induce alkalosis. For example, if the cause of metabolic alkalosis is due to loss of gastric acid, manifestations would include vomiting with or without diarrhea. If the cause is due to hyperaldosteronism, clinical manifestation may be hypertension, peripheral edema, and signs of fluid overload.

More importantly, signs of hypokalemia (whether the cause or consequence of metabolic alkalosis) is most worrisome as they will affect all electrically excitable tissue such as the nervous system, heart, and muscles. Nervous symptoms may be dizziness, paresthesia, tingling, or changes in cognition. Cardiac symptoms may be abnormal rate (tachycardia) and/or rhythm. Muscular signs may be muscle weakness or twitching.

Patients present with dyspnea, fever, chills, peripheral edema, orthopnea, dizziness, paresthesia, abdominal pain, nausea, vomiting, or tinnitus. Neuropathic symptoms such as tingling, numbness, muscle weakness, twitching. ^[4]

References

1. 1. Acid Base Disorders
   2. Fluid, Electrolyte and Acid-Base Disorders: Clinical Evaluation and Management
   3. Acute Kidney Injury
   4. Alkalosis
   5. https://www.uptodate.com/contents/causes-of-metabolic-alkalosis#H37637759