Metabolic Alkalosis causes, pathophysiology and treatment

Metabolic Alkalosis

1. METABOLIC ALKALOSIS DR.VASANTHAKUMARI U

2. Definition:A primary increase in serum bicarbonate concentration. Mechanism:Caused by hydrogen ion loss or bicarbonate gain. Compensation:Hypoventilation to increase CO2 levels. Impact:Can lead to hypokalemia and electrolyte imbalances. Importance:Early identification and treatment are crucial.

3. CAUSES Exogenous HCO3- Loads:Acute alkali administration, milk-alkali syndrome. ECFV Contraction, Normotension, K+ Deficiency:Vomiting , gastric aspiration, congenital chloridorrhea , villous adenoma. Renal Origin:Diuretics , posthypercapnic state, hypercalcemia, hypoparathyroidism. Recovery from Acidosis:Recovery from lactic acidosis or ketoacidosis. Nonreabsorbable Anions:Including penicillin, carbenicillin.

4. Magnesium Deficiency:Mg2+ deficiency leading to alkalosis. Potassium Depletion:K + depletion and its role in alkalosis. Bartter’s Syndrome:Loss of function mutations of transporters in TALH. Gitelman’s Syndrome:Loss of function mutation in Na+-Cl- cotransporter in DCT. High Renin States:Renal artery stenosis, accelerated hypertension, renin-secreting tumors, estrogen therapy.

5. Primary Aldosteronism:Adenoma , hyperplasia, carcinoma. Adrenal Enzyme Defects:11 β- Hydroxylase deficiency, 17 α- Hydroxylase deficiency. Cushing's Syndrome/ Disease:Excess cortisol production. Other Causes:Licorice , carbenoxolone, chewer’s tobacco. Gain-of-Function Mutations:Mutations in renal sodium channels, e.g., Liddle’s syndrome.

6. Initial Assessment:Clinical history and physical examination. Laboratory Tests:Serum electrolytes, blood gas analysis, urine chloride concentration. Additional Tests:Hormonal assays (renin, aldosterone), imaging studies for adrenal or renal abnormalities. Differential Diagnosis:Rule out other causes of alkalosis (respiratory alkalosis). Confirmatory Tests:Specific tests based on suspected underlying cause (genetic testing, urine studies).

7. Treat Underlying Cause:Correct primary disorder (e.g., discontinue diuretics, treat hyperaldosteronism). Electrolyte Management:Potassium and magnesium supplementation. Fluid Therapy:Intravenous saline for volume depletion. Medications:Carbonic anhydrase inhibitors (e.g., acetazolamide) for bicarbonate excretion. Monitoring:Regular follow-up of blood gases, electrolytes, and clinical symptoms.

8. Acute Alkali Administration Common Sources and Examples:Overuse of antacids (e.g., sodium bicarbonate). Excessive intake of alkaline medications. Clinical Scenarios:Often seen in patients self-medicating for dyspepsia or chronic kidney disease. Can occur in a hospital setting due to administration errors.

9. Milk-Alkali Syndrome Pathophysiology:Caused by excessive intake of calcium and absorbable alkali. Leads to hypercalcemia and renal impairment. Risk Factors and Prevalence: Common in individuals consuming large amounts of calcium carbonate supplements. Increased incidence with the use of calcium for osteoporosis prevention.

10. Effective ECFV Contraction Effective extracellular fluid volume (ECFV) contraction refers to a perceived or actual decrease in the volume of fluid in the extracellular space. Normotension K+ Deficiency Secondary Hyperaldosteronism: Increased aldosterone production in response to decreased ECFV.

11. Gastrointestinal Origin Vomiting Mechanism: Loss of stomach acid (HCl) through vomiting reduces the amount of acid in the body, leading to alkalosis. Common in conditions like gastroenteritis, pyloric stenosis, and during chemotherapy. Gastric Aspiration Mechanism: Aspiration of gastric contents removes acid from the body.

12. Congenital Chloridorrhea A rare genetic disorder characterized by excessive chloride loss in stool. Mutations in the SLC26A3 gene leading to defective chloride-bicarbonate exchange in the intestine. Clinical Presentation:Chronic diarrhea, abdominal distension, and failure to thrive in infants. Diagnosis:Elevated stool chloride levels, genetic testing. Management:Electrolyte supplementation, dietary modifications.

13. Villous Adenoma A type of polyp found in the colon with a high risk of malignancy. Secretes large amounts of mucous rich in bicarbonate, leading to metabolic alkalosis. Symptoms include diarrhea, rectal bleeding, and abdominal pain. Colonoscopy and histological examination. Surgical removal and regular follow-up.

14. Renal Origin Metabolic alkalosis can originate from various renal causes Common Causes:Diuretics , posthypercapnic state, and electrolyte imbalances. Impaired renal bicarbonate excretion or increased renal bicarbonate reabsorption. Clinical Manifestations:Muscle cramps, weakness, and cardiac arrhythmias.

15. Diuretics Types:Loop diuretics (e.g., furosemide), thiazides. Mechanism:Increase renal excretion of sodium and chloride, leading to volume contraction and increased bicarbonate reabsorption. Commonly causes metabolic alkalosis in patients with heart failure or hypertension. Symptoms:Dehydration , muscle cramps, and arrhythmias. Management:Dose adjustment, potassium-sparing diuretics, and electrolyte monitoring.

16. Posthypercapnic State Metabolic alkalosis following the correction of chronic respiratory acidosis. Renal compensation leads to bicarbonate retention during chronic hypercapnia, which persists after CO2 levels normalize. Seen in patients with chronic obstructive pulmonary disease (COPD) after ventilation.

17. Hypercalcemia/Hypoparathyroidism Mechanism: Hypercalcemia can cause renal bicarbonate retention; hypoparathyroidism leads to decreased calcium and compensatory alkalosis. Symptoms of hypercalcemia include polyuria, polydipsia, and nephrolithiasis. Blood tests for calcium, parathyroid hormone (PTH), and bicarbonate levels. Address underlying hypercalcemia or hormone replacement in hypoparathyroidism. Regular follow-up of calcium and bicarbonate levels.

18. Recovery from Lactic Acidosis or Ketoacidosis Mechanism: Bicarbonate levels rise as acidosis is corrected and excess organic acids are metabolized. Seen in diabetic ketoacidosis (DKA) and severe sepsis after treatment. Fatigue, confusion, and electrolyte imbalances. Gradual correction of underlying acidosis, close monitoring of electrolytes.

19. Nonreabsorbable Anions Examples:Penicillin , carbenicillin, and other nonreabsorbable anions. Mechanism:These anions bind with sodium in the renal tubules, leading to increased bicarbonate reabsorption. Can cause metabolic alkalosis in patients on high doses of these antibiotics. Management:Adjusting antibiotic dosage, monitoring renal function.

20. Mg2+ Deficiency Pathophysiology: Magnesium deficiency impairs renal potassium retention, leading to hypokalemia and metabolic alkalosis. Clinical Significance:Common in malnutrition, chronic alcoholism, and certain medications. Symptoms:Muscle cramps, seizures, and cardiac arrhythmias. Treatment:Magnesium supplementation, addressing the underlying cause.

21. K+ Depletion Mechanism:Low potassium levels stimulate renal bicarbonate reabsorption and hydrogen ion excretion. Common Causes:Diuretics , vomiting, diarrhea, and certain medications. Symptoms:Weakness , muscle cramps, and arrhythmias. Management:Potassium supplementation, dietary modifications, and addressing the underlying cause.

22. Bartter's Syndrome A rare inherited disorder affecting the kidneys' ability to reabsorb sodium and chloride. Pathophysiology:Caused by mutations affecting ion channels and transporters in the thick ascending limb of Henle's loop (TALH). Clinical Features:Hypokalemia , metabolic alkalosis, hyperreninemia, and hyperaldosteronism. Diagnosis:Genetic testing, serum electrolytes, renin, and aldosterone levels.

23. Gitelman's Syndrome A genetic disorder similar to Bartter's syndrome but affecting the distal convoluted tubule (DCT). Mutations in the gene encoding the thiazide-sensitive Na-Cl cotransporter. Clinical Features:Hypokalemia , hypomagnesemia, metabolic alkalosis, and low blood pressure. Diagnosis:Genetic testing,serum electrolytes, magnesium, and urinary calcium excretion.

24. ECFV Expansion, Hypertension, K+ Deficiency, and Mineralocorticoid Excess Metabolic alkalosis associated with extracellular fluid volume (ECFV) expansion and increased mineralocorticoid activity. Seen in conditions like hyperaldosteronism and certain adrenal enzyme defects. Symptoms:Hypertension , muscle weakness, and alkalosis. Diagnosis:serum electrolytes, renin, and aldosterone levels. .

25. High Renin States Conditions with elevated renin levels leading to secondary hyperaldosteronism. Common Causes:Renal artery stenosis, accelerated hypertension, renin-secreting tumors, and estrogen therapy. Clinical Features:Hypertension , hypokalemia, and metabolic alkalosis. Diagnosis:Renal imaging, blood tests for renin and aldosterone levels. Management:Treating the underlying cause, antihypertensive medications.

26. Renal Artery Stenosis Narrowing of the renal arteries leading to decreased kidney perfusion. Reduced renal blood flow triggers renin release, causing secondary hyperaldosteronism. Resistant hypertension, hypokalemia, and metabolic alkalosis. Diagnosis:Renal Doppler ultrasound, CT angiography, MR angiography.

27. Accelerated Hypertension A severe form of hypertension with rapid onset and progression. Marked elevation in blood pressure leading to endothelial damage and renin release. Clinical Features:Severe headache, visual disturbances, and symptoms of hypertensive encephalopathy. Blood pressure measurement, fundoscopic exam, renal function tests. Immediate antihypertensive therapy, often in an ICU setting.

28. Renin-Secreting Tumor A rare tumor that secretes excess renin, causing secondary hyperaldosteronism. Pathophysiology:Excess renin leads to increased aldosterone production, hypertension, and metabolic alkalosis. Clinical Features:Severe hypertension, hypokalemia, and muscle weakness. Imaging studies (CT, MRI), serum renin and aldosterone levels. Management:Surgical removal of the tumor, antihypertensive medications.

29. Estrogen Therapy Estrogen increases renin substrate production, leading to increased renin and aldosterone levels. Seen in patients undergoing hormone replacement therapy or certain contraceptive methods. Hypertension, hypokalemia, and metabolic alkalosis. Diagnosis:serum electrolytes, renin, and aldosterone levels. Management:Adjusting estrogen dosage, switching to alternative therapies.

30. Low Renin States Conditions with low renin levels but high aldosterone production. Common Causes:Primary aldosteronism, adrenal hyperplasia, and adrenal carcinoma. .

31. Primary Aldosteronism A condition characterized by excessive aldosterone production from the adrenal glands. Common Causes:Adenoma , hyperplasia, carcinoma. Clinical Features:Hypertension , hypokalemia, metabolic alkalosis. Serum aldosterone and renin, adrenal imaging. Surgical removal of adenomas, aldosterone antagonists.

32. Adrenal Enzyme Defects Genetic defects in enzymes involved in cortisol and aldosterone synthesis. Common Defects:11 β- hydroxylase deficiency, 17 α- hydroxylase deficiency. Hypertension, hypokalemia, metabolic alkalosis, ambiguous genitalia in some cases. Diagnosis:Hormonal assays, genetic testing. Management:Hormone replacement therapy, surgical intervention for ambiguous genitalia.

33. 11β- Hydroxylase Deficiency A genetic disorder affecting cortisol synthesis, leading to excess mineralocorticoid activity. Reduced cortisol production causes increased ACTH, leading to adrenal hyperplasia and excess deoxycorticosterone. Hypertension, hypokalemia, virilization in females. Hormonal assays, genetic testing. Glucocorticoid replacement, blood pressure control.

34. 17α- Hydroxylase Deficiency A genetic disorder affecting cortisol and sex steroid synthesis. Reduced cortisol and sex steroids lead to increased ACTH, adrenal hyperplasia, and excess deoxycorticosterone. Hypertension, hypokalemia, delayed puberty, and ambiguous genitalia. Diagnosis:Hormonal assays, genetic testing. Glucocorticoid and sex steroid replacement, surgical intervention for genital anomalies.

35. Cushing's Syndrome or Disease A condition characterized by excessive cortisol production (syndrome) or due to an ACTH-secreting pituitary tumor (disease). Excess cortisol leads to hypertension, hypokalemia, and metabolic alkalosis. Central obesity, moon face, buffalo hump, muscle weakness. Diagnosis:24-hour urinary free cortisol, dexamethasone suppression test, pituitary MRI. Surgery for pituitary adenomas, medications to reduce cortisol production.

36. Other Causes: Licorice, Carbenoxolone, Chewer’s Tobacco These substances inhibit 11 β- hydroxysteroid dehydrogenase, increasing cortisol activity and mimicking mineralocorticoid excess. Chronic consumption can lead to hypertension, hypokalemia, and metabolic alkalosis. Weakness, muscle cramps, and high blood pressure. Diagnosis:History of substance use, blood tests for electrolytes, and cortisol. Discontinuation of the causative substance, electrolyte correction.

37. Liddle's Syndrome A genetic disorder characterized by increased activity of the epithelial sodium channel (ENaC). Mutations in the SCNN1B or SCNN1G genes lead to sodium retention and potassium excretion. Potassium-sparing diuretics (e.g., amiloride).