SEARCH RESULTS FOR: Primary-Aldosteronism-Pathogenesis

Primary Aldosteronism Pathogenesis

Primary Aldosteronism: Pathogenesis and clinical findings Unilateral aldosterone producing adenoma Benign tumours of the adrenal glands develop ion channel mutations ↑ Na+ movement into adrenal gland cellsàcell depolarizationà↑ Ca+ entry into zona glomerulosa Bilateral adrenal hyperplasia Unknown mechanisms cause bilateral adrenal hyperplasia of the zona glomerulosa ↑ Ca+ leads to cellular replication and hyperplasia of the zona glomerulosaà ↑aldosterone release Adrenocortical carcinoma Abnormal and excessive growth of the zona glomerulosa (neoplasia)à↑ aldosterone Overproduction of aldosterone, independent from renin-angiotensin- aldosterone system (RAAS) Ectopic aldosterone secreting tumor adrenocortical tissue outside of the adrenal glands produce aldosterone Familial hyperaldosteronism (FH) Type I Rare mutation causing ACTH- sensitive aldosterone production in the zona fasciculata Aldosterone binds its receptor on the principal cells located in the collecting duct of the kidney ↑ Na+ and K+ channel insertion on luminal surface of the principal cell and ↑ Na/K ATPase activity on basolateral surface Na+ follows the concentration gradient and moves into the principal cell cytoplasmàK+ moves into the collecting duct to maintain electroneutrality Aldosterone binds its receptor on the alpha intercalated cells located in the late distal tubule and collecting duct of the kidney ↑ H+ ATPase and Na/H+ ATPase activity on the luminal surface of alpha intercalated cellsà↑ H+ excretion H+ loss permits HCO3- to move down the electrochemical gradient across the luminal surfaceà↑ HCO3- resorption into peritubular capillaries Metabolic alkalosis K+ efflux (or hypokalemia of any etiology) is counterbalanced by influx of H+ into tubular cells to maintain electroneutrality ↓ pH in tubular cells activates glutaminase (a pH dependent enzyme) generating glutamate from glutamine Glutamate within renal tubules dissociates into NH4+, HCO3- Intracellular acidosis within tubular cells Disrupted cellular signaling within the collecting duct results in reduced APQ2 translocation to luminal surface Authors: Kyle Moxham Reviewers: Emily Wildman Austin Laing Yan Yu* Matthew Harding* * MD at time of publication Hypertension ↑ Na+ reabsorption H2O follows active reabsorption of solute into circulationà ↑ effective arterial blood volume (EABV) Chronic EABV expansion resets hypothalamic osmotic sensitive ADH releaseàdecreased ADH production ↑ K+ excretion Hypokalemia (see our Hypokalemia: Clinical Findings Slide) ↓ Na+ delivery to macula densa in the distal convoluted tubule ↓Endogenous renin secretion by juxtaglomerular apparatus while aldosterone continues to be independently produced Polydipsia & Polyuria Mild hypernatremia ↓ Renin: Aldosterone ratio Nephrogenic diabetes insipidus: ↓ urinary concentrating ability Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2021 on www.thecalgaryguide.com