Metabolic Alkalosis: Pathogenesis
Authors: Wazaira Khan Reviewers: Jessica Krahn, Emily Wildman, Austin Laing, Huneza Nadeem, Ran (Marissa) Zhang, Adam Bass* * MD at time of publication
Primary hyperaldosteronism E.g., aldosterone- secreting mass, adrenal hyperplasia
Secondary hyperaldosteronism E.g., renin-secreting mass, renal artery stenosis
Pseudo- hypoaldosteronism E.g., Liddle’s Syndrome
Unregulated aldosterone production in adrenal cortex
Excess aldosterone suppresses renin production
Unregulated renin production by juxtaglomerular cells
Sustained ↑ in mineralocorticoid (aldosterone) activity
Insertion of epithelial sodium channels on principal cells in collecting duct
↑ Water retention by the kidney
↑ Na+ reabsorption by principal cells
↑ EABV
• ↑ Jugular venous pressure • Hypertension
• Urine Na+ > 40 mEq/L
Low renin, high aldosterone state
Activation of renin- angiotensin-aldosterone system (RAAS)
Release of aldosterone from adrenal cortex
High renin, high aldosterone state
↑ Negative charge in collecting duct lumen
K+ leaks into collecting duct lumen by principal cell to maintain electroneutrality
Hypokalemia
Intracellular K+ leaks out of any cell in the body to compensate for low serum K+ levels
Extracellular H+ enters cell to maintain electroneutrality
Intracellular acidosis
Activation of compensatory acid secreting mechanisms in kidney
Impaired tubular function
E.g., loop/thiazide diuretics, Bartter’s/ Gitelman’s Syndrome
Upper GI Loss
E.g., vomiting, nasogastric suction
Unregulated epithelial sodium channel activity in collecting duct mimicking aldosterone function
↑ in Na+ and water retention à RAAS inhibition
↓ Na+ and Cl- reabsorption in thick ascending limb or distal convoluted tubule
Low renin, low aldosterone state
↑ Na+, Cl- and water secretion through kidney
RAAS activation
See “Physiology of RAAS” slide
↓ EABV • • •
Temporary ↑ in mineralocorticoid (aldosterone) activity
↓ Jugular venous pressure Orthostatic hypotension Dry mucous membranes Urine Na+ < 20 mEq/L • Loss of fluid through GI tract ↓ HCl delivery to small intestine ↑ NH + secretion and 4 ↑ HCO3- reabsorption in proximal tubule ↑ H+ secretion in cortical collecting duct Loss of gastric contents, including HCl ↓ HCO3- secretion by pancreas, liver and intestines to neutralize HCl Loss of intrinsic acid to neutralize HCO3- ↑ Plasma [HCO3-] Metabolic Alkalosis Arterial blood gas pH > 7.40 Plasma [HCO3-] > 24 mEq/L
Effective Arterial Blood Volume (EABV): component of arterial blood volume that is effectively perfusing organs
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published May 31, 2022 on www.thecalgaryguide.com