Overview
This lecture covers metabolic alkalosis, focusing on its differential diagnosis, underlying mechanisms, common and rare causes, and a stepwise clinical approach to identifying its etiology.
Classification of Metabolic Alkalosis
- Causes are classified by organ (GI tract or kidneys) and mechanism (hydrogen loss or bicarbonate gain).
- Common mechanisms: loss of hydrogen via vomiting/NG suction or diuretics; gain of bicarbonate via milk alkali syndrome or sodium bicarbonate ingestion.
Common and Uncommon Causes
- Common causes: contraction alkalosis (volume depletion), diuretics, vomiting, NG suction.
- Uncommon causes: mineralocorticoid excess, hypokalemia, milk alkali syndrome, sodium bicarbonate ingestion, Bartter and Gitelman syndromes, congenital chloride diarrhea.
Pathophysiology of Common Causes
Contraction Alkalosis
- Triggered by volume depletion or decreased effective circulation (e.g., heart failure).
- Low blood volume increases renin, angiotensin II, and aldosterone, promoting sodium/bicarbonate reabsorption and hydrogen secretion, causing alkalosis.
Diuretics
- Loop and thiazide diuretics inhibit sodium reabsorption in the nephron, causing dehydration or increased sodium delivery to the collecting duct, leading to hydrogen/potassium secretion and alkalosis.
Vomiting and NG Suction
- Directly remove hydrogen ions and cause volume depletion, leading to both direct and secondary contraction alkalosis.
Pathophysiology of Uncommon Causes
Mineralocorticoid Excess
- Presents with hypertension, hypokalemia, and alkalosis; due to hyperaldosteronism (primary or secondary), Cushing syndrome, or rare disorders (e.g., Liddle syndrome).
Hypokalemia
- Promotes intracellular hydrogen shifts and increased renal bicarbonate reabsorption, contributing to alkalosis.
Milk Alkali Syndrome
- Results from high intake of calcium and absorbable alkali, presenting with hypercalcemia, alkalosis, and renal insufficiency.
Bartter and Gitelman Syndromes
- Genetic defects in nephron transporters; mimic loop (Bartter) or thiazide (Gitelman) diuretic effects; characterized by alkalosis, hypokalemia, and high renin/aldosterone without hypertension.
Diagnostic Approach
- First, assess volume status: low volume suggests common causes; normal/high volume requires assessment of blood pressure and potassium.
- Hypertension suggests mineralocorticoid excess; check renin and aldosterone levels to differentiate primary/secondary/other causes.
- Consider rare syndromes or exogenous/substance causes if routine workup is negative.
Key Terms & Definitions
- Metabolic Alkalosis — Increase in blood pH due to primary excess of bicarbonate or loss of hydrogen.
- Contraction Alkalosis — Alkalosis from volume depletion and increased hormone-driven kidney reabsorption.
- Mineralocorticoid — Steroid hormone (e.g., aldosterone) that increases sodium reabsorption in the kidney.
- Milk Alkali Syndrome — Triad of hypercalcemia, metabolic alkalosis, and renal insufficiency from calcium/alkali ingestion.
- Bartter Syndrome — Rare inherited defect in thick ascending limb transporter, mimics loop diuretics.
- Gitelman Syndrome — Rare inherited defect in distal tubule transporter, mimics thiazide diuretics.
- Hyperaldosteronism — Excess aldosterone production, either primary (adrenal) or secondary (renin-driven).
Action Items / Next Steps
- Review upcoming lectures on primary respiratory disorders.
- Study kidney hormone regulation and nephron transporter functions for better understanding of acid-base disturbances.