bubble_chart Overview

Metabolic alkalosis is characterized by an increase in HCO₃- (>26 mmol/L) and elevated pH (>7.45) in the body.

bubble_chart Etiology

The fundamental cause of metabolic alkalosis is the loss of acid (H⁺) or the gain of base (HCO₃^-). It commonly occurs in the following situations: a. Excessive loss of H⁺, such as persistent vomiting (pyloric obstruction) or continuous gastrointestinal decompression; b. Excessive intake of HCO₃^-, such as ingesting large amounts of sodium bicarbonate for peptic ulcers; c. Excessive chloride excretion due to diuresis, leading to excessive loss of Cl^- and Na⁺ in the urine, resulting in hypochloremic alkalosis. When plasma HCO₃^- levels rise, blood pH increases, inhibiting the respiratory center and causing slower, shallower breathing to retain CO₂. This increases blood H2CO₃ to compensate. Simultaneously, the renal tubules reduce the generation of H⁺ and NH₃, while increasing the excretion of HCO₃^- in the urine, thereby restoring the plasma HCO₃^-/H₂CO₃ ratio to 20:1.

bubble_chart Pathogenesis

1. Excessive loss of hydrogen ions

(1) Gastric fluid loss: Commonly seen in severe vomiting due to pyloric obstruction or high intestinal obstruction, where gastric acid (HCl) is directly lost. Gastric parietal cells produce HCl, with H⁺ derived from the reaction CO₂+H₂O→H₂CO₃→H⁺＋HCO₃^- in the parietal cells, while Cl^- comes from plasma. Carbonic anhydrase in parietal cells accelerates this reaction. H⁺ and Cl^- combine in the gastric gland lumen to form HCl, which is secreted into the stomach. Upon entering the small intestine, HCl is neutralized by NaHCO₃ in alkaline digestive fluids such as intestinal juice, pancreatic juice, and bile. The secretion of alkaline fluids is stimulated by the entry of H⁺ into the intestine. Therefore, if HCl is lost due to vomiting, the secretion of NaHCO₃ in intestinal fluid decreases, leading to retention in the body. Moreover, NaHCO₃ already secreted into the intestine is not neutralized by HCl, inevitably causing an increase in [HCO₃^-] in intestinal fluid and enhancing its reabsorption. This raises the blood [HCO₃^-], resulting in metabolic alkalosis.

Significant gastric fluid loss may also be accompanied by the loss of Cl⁺

and K⁺, as well as reduced extracellular fluid volume, which are also factors contributing to metabolic alkalosis in this context. Low blood Cl^- leads to an increase in the negatively charged ion HCO₃^- to compensate, while low blood K⁺ causes H⁺ to move into cells due to ion shifts. Reduced extracellular fluid volume increases aldosterone secretion, promoting Na⁺ reabsorption and enhancing the excretion of H⁺ and K⁺, all of which can lead to metabolic alkalosis.

(2) Excessive renal excretion of H⁺: Increased renal excretion of H⁺ is primarily caused by elevated aldosterone secretion. Aldosterone promotes the excretion of H⁺ and K⁺ in the distal convoluted tubules and collecting ducts while enhancing Na⁺ reabsorption. Increased H+ _{excretion results from the reaction H}2_COH3^→H+_＋HCO3-_{, leading to greater HCO}3- ^{generation, which is reabsorbed along with Na}+{|189|}, thereby causing metabolic alkalosis and concurrent hypokalemia.

Increased aldosterone secretion is observed in the following conditions: ① Primary hyperaldosteronism. ② Cushing's Syndrome—often caused by ACTH-secreting pituitary tumors, primary adrenal cortical hyperplasia, or tumors. The increased production and release of hormones such as cortisol, which also has mineralocorticoid activity, can lead to metabolic alkalosis. ③ Congenital adrenal hyperplasia—divided into two types: 17-hydroxylase deficiency (non-virilizing) and 11-hydroxylase deficiency (virilizing). The deficiency of these enzymes reduces cortisol synthesis, leading to decreased blood cortisol levels, which feedback to cause excessive ACTH secretion by the pituitary, promoting adrenal cortical synthesis and secretion of more deoxycorticosterone (DOC) and corticosterone. DOC exhibits significant mineralocorticoid activity. ④ Bartter's Syndrome—a syndrome characterized by hyperplasia of the juxtaglomerular apparatus and increased renin secretion. The renin-angiotensin-aldosterone system leads to increased aldosterone secretion. The absence of hypertension in patients is due to reduced vascular responsiveness to angiotensin II. Because patients have increased prostaglandin secretion, recent studies suggest that sympathetic stimulation increases prostaglandins, thereby enhancing renin secretion. For example, using indomethacin to inhibit prostaglandin synthesis can lower renin and aldosterone levels in patients and restore metabolic alkalosis and Na⁺

, K⁺ to normal. ⑤ Juxtaglomerular apparatus tumors, whose cells secrete large amounts of renin, causing hypertension and metabolic alkalosis. ⑥ Prolonged and excessive use of Liquorice Root and its preparations—since glycyrrhizic acid has mineralocorticoid activity, it can cause metabolic alkalosis similar to hyperaldosteronism. ⑦ Reduced extracellular fluid volume increases aldosterone secretion to enhance Na⁺ reabsorption and preserve volume, which can lead to metabolic alkalosis. This commonly occurs with loop diuretics like furosemide and ethacrynic acid or significant gastric fluid loss. In such cases, for every 1-liter reduction in extracellular fluid, plasma [HCO₃^-] increases by approximately 1.4 mmol/L. Besides reducing extracellular fluid, furosemide and ethacrynic acid inhibit the reabsorption of Cl^- and Na⁺ in the ascending limb of the loop of Henle, increasing the delivery of Na⁺ to the distal tubule and enhancing the distal tubule's H⁺ secretion in exchange for Na⁺, which also contributes to metabolic alkalosis. ⑧ Stress responses during trauma and surgery increase adrenal cortical hormone secretion, often accompanied by metabolic alkalosis.

2. Excessive intake of alkaline substances

(1) Excessive bicarbonate intake: For example, ulcer patients taking excessive sodium bicarbonate to neutralize stomach acid can lead to a significant increase in intestinal NaHCO₃, especially in patients with impaired kidney function. Due to the decreased ability of the kidneys to regulate HCO₃^-, alkalosis can occur. Additionally, excessive administration of sodium bicarbonate when correcting acidosis can also lead to alkalosis.

(2) Excessive lactate intake: Metabolized by the liver to produce HCO₃^-. Seen when excessive lactate solution is administered to correct acidosis.

(3) Excessive citrate intake: Citrate is commonly used as an anticoagulant in blood transfusions. Every 500 milliliters of blood contains 16.8 mEq of citrate, which is metabolized by the liver to produce HCO₃^-. Therefore, massive blood transfusions (e.g., rapid infusion of 3000–4000 milliliters) can lead to metabolic alkalosis.

3. Potassium deficiency

A decrease in serum potassium due to various causes can lead to an increase in plasma NaHCO₃

and result in metabolic alkalosis. The mechanisms include: ① When serum K⁺ decreases, renal tubular epithelial cells correspondingly reduce K⁺ excretion and increase H⁺ excretion, exchanging for increased Na⁺ and HCO₃^-. In this case of metabolic alkalosis, unlike typical alkalosis where alkaline urine is excreted, acidic urine is excreted instead, termed paradoxical acidic urine. ② When serum potassium decreases, due to ion exchange, K⁺ moves out of cells to replenish extracellular K⁺, while H⁺ enters cells to maintain electrical neutrality, thus leading to metabolic alkalosis (though intracellular acidosis occurs, intracellular buffers can mitigate the entering H⁺).

4. Chloride deficiency

Since Cl^- is the only anion in the renal tubules that is easily reabsorbed in conjunction with Na⁺, when the [Cl^-] in the original urine decreases, the renal tubules increase the excretion of H⁺ and K⁺ to exchange for Na⁺, leading to increased reabsorption of HCO₃^- and thus the production of NaHCO₃. Therefore, in hypochloremia, due to the loss of H⁺ and K⁺ and increased NaHCO₃ reabsorption, metabolic alkalosis can occur. In this seasonal disease, urinary Cl^- is decreased. Additionally, the aforementioned furosemide and ethacrynic acid can inhibit the active reabsorption of Cl^- in the thick ascending limb of the loop of Henle, leading to Cl^- deficiency. In this case, the distal convoluted tubule increases the excretion of H⁺ and K⁺ to exchange for the excessive Na⁺ reaching the distal convoluted tubule. Thus, metabolic alkalosis can also occur. In this seasonal disease, urinary Cl^- is increased.

Vomiting loses HCl, which means losing Cl^-. The Cl^- levels in plasma and urine decrease, and through the aforementioned mechanism of reduced Cl^- in the original urine, metabolic alkalosis is promoted.

bubble_chart Clinical Manifestations

a. Shallow and slow breathing (retaining CO₂, leading to increased blood H₂CO₃); b. Mental symptoms: agitation, excitement, delirious speech, drowsiness, and in severe cases, unconsciousness; c. Increased neuromuscular excitability, with symptoms such as hand and foot convulsions, hyperactive tendon reflexes, etc.; d. Elevated blood pH and SB, increased CO₂CP, BB, and BE, and possible decreases in blood K⁺ and Cl^-.

bubble_chart Diagnosis

Based on medical history and clinical manifestations, a preliminary diagnosis can be made, and blood gas analysis can confirm the diagnosis and its severity. In decompensation, blood pH and [HCO₃^-] are significantly increased, while P_CO2 is normal; in partial compensation, blood pH, [HCO₃^-], and P_CO2] are all elevated to some extent.

bubble_chart Treatment Measures

1. Actively prevent and treat the primary diseases causing metabolic alkalosis and eliminate the disease cause.

2. Correct hypokalemia or hypochloremia, such as supplementing KCl, NaCl, CaCl₂, NH₄Cl, etc. Among them, NH₄Cl can correct both alkalosis and supplement Cl^-, but it should not be used in patients with liver dysfunction, as NH₄Cl requires hepatic metabolism.

3. Correct alkalosis

- Grade I alkalosis can be effectively treated with isotonic saline infusion, as the Cl^- content in saline is about 1/3 higher than that in serum, thereby correcting hypochloremic alkalosis. - Severe alkalosis patients may be given a certain amount of acidic drugs, such as arginine or ammonium chloride.

- The required acid dose can be calculated using the following formula:

**Acid dose (mmol) = (measured SB or CO₂CP - normal SB or CO₂CP) × body weight (kg) × 0.2**

- Carbonic anhydrase inhibitors, such as acetazolamide, can be used to inhibit the synthesis of H₂CO₃ in renal tubular epithelial cells, thereby reducing H⁺ excretion and HCO₃^- reabsorption. - Dilute HCl can also be used to neutralize excess NaHCO₃ in body fluids. Approximately 1 mEq of acid can reduce plasma [HCO₃^-] by about 5 mEq/L. - Aldosterone antagonists can reduce the renal excretion of H⁺ and K⁺, providing certain therapeutic effects.