Nephrology: NaCl Cotransporter Function

Metabolic Alkalosis

• High concentrations of poorly reabsorbable anions in the distal renal tubule increase luminal flow rate and luminal electronegativity, leading to enhanced secretion of potassium and hydrogen ions, resulting in hypokalemia and metabolic alkalosis.

Factors Contributing to Metabolic Alkalosis

• Primary hyperaldosteronism (e.g., chronic hypertension) and secondary hyperaldosteronism (e.g., dehydration, CHF, chronic use of diuretics, and sepsis) contribute to metabolic alkalosis.
• Hepatorenal syndrome in liver cirrhosis: RAAS overactivation to maintain perfusion to the liver.

Regulation of Sodium Reabsorption

• Sodium is mostly reabsorbed (70%) passively in the proximal tubules due to hyperosmolarity from surrounding tissues after filtration.
• 30-40% of sodium is reabsorbed in the loop of Henle and distal convoluted tubules, influenced by aldosterone.

Intracellular Shift of Hydrogen and Retention/Addition of Bicarbonate

• Hydrogen ions are shifted intracellularly, leading to an imbalance in the buffer system and a relative increase in bicarbonate.
• Processes that drive hydrogen intracellularly include hypokalemia.
• The net concentration of bicarbonate increases, resulting in metabolic alkalosis.

Maintenance of Metabolic Alkalosis

• Abnormality in renal function prevents the excretion of excess bicarbonate, leading to metabolic alkalosis.
• Hypovolemia, hypokalemia, hypochloremia, reduced glomerular filtration rate, and hyperaldosteronism can impair the ability to eliminate bicarbonate, perpetuating metabolic alkalosis.

Effects of Hypovolemia

• Hypovolemia reduces effective arterial blood volume, leading to decreased renal perfusion and increased aldosterone secretion.
• Decreased filtered chloride is a major stimulus for aldosterone secretion, which enhances sodium absorption in the collecting tubules.

Effects of Hypokalemia

• Hypokalemia exacerbates hypovolemia, decreases GFR, and promotes bicarbonate resorption.
• Low potassium increases sodium delivery to the distal nephron, leading to increased hydrogen excretion and bicarbonate retention.

Treatment of Metabolic Alkalosis

• Administration of chloride as hypertonic NaCl, with supplemental potassium, can restore circulating volume and provide sodium and chloride to decrease distal sodium delivery and remove the stimulus for aldosterone secretion and acid excretion.

Paradoxical Aciduria in Metabolic Alkalosis

• Vomit-induced metabolic alkalosis can lead to paradoxical aciduria due to increased renal acid excretion.

Differential Diagnosis of Metabolic Alkalosis

• Etiology of metabolic alkalosis includes vomiting, diarrhea, primary or secondary hyperaldosteronism, and other factors.

Pathways Leading to Metabolic Alkalosis

• Volume contraction, dyselectrolytemia, and other mechanisms can lead to metabolic alkalosis.

Compensation for Metabolic Alkalosis

• Respiratory response to metabolic alkalosis is hypoventilation, which results in an increased PaCO2.
• Respiratory compensation is initiated within hours when the central and peripheral chemoreceptors sense an increase in pH.
• PaCO2 increases by 0.6 mmHg for every mmol/l that HCO3- is above 24 mmol/l within 1-1.5 days.