SEARCH RESULTS FOR: Primary-Aldosteronism

Primary-Aldosteronism

Primary Aldosteronism: Clinical findings Note: This condition is also known as “Primary Hyper-Aldosteronism” or “Conn’s Syndrome” Authors: Samin Dolatabadi Reviewers: Amanda Henderson, Hannah Yaphe, Yan Yu*, Hanan Bassyouni* Juliya Hemmett* * MD at time of publication ↑ Expression of Cl-/HCO3- exchanger in the basolateral membrane of intercalated cell of cortical collecting duct ↑ HCO3- reabsorption into bloodstream ↑ Autonomous aldosterone secretion from zona glomerulosa of adrenal cortex (e.g. aldosterone producing adenoma) ↑ Serum aldosterone level ↑ Circulating aldosterone activates mineralocorticoid receptors on cardiac myocytes ↑ Transcription of proinflammatory and profibrotic genes in cardiac myocytes Cardiac fibrosis and hypertrophy In the rest of the body, K+ moves from intracellular to extracellular environment (down it's concentration gradient) to compensate for decreased serum K+ Loss of positively charged K+ànegative intracellular chargeàcells take up H+ to remain electrostatically neutral ↑ Expression of epithelial sodium channels in principal cells of cortical collecting duct ↑ Na+ reabsorption from cortical collecting duct into blood vessels + Water follows Na into the blood vessels to balance the osmotic pressure between the blood and the renal tubules ↑ blood volume within the volume- constrained space of blood vessels ↑ Activation of Na+/K+ ATPase in principle cells of cortical collecting duct Removal of positively charged Na+ from tubular lumenà lumen becomes electronegative versus the interstitial space & inside tubular epithelial cells Positively charged K+ follows the electrical gradient and is secreted into tubular lumen ↓ Serum K+ concentration ↑ Expression of H+ ATPase in the apical (luminal) membrane of intercalated cell of cortical collecting duct H+ is secreted into cortical collecting duct → renal loss of H+ from the body Metabolic Alkalosis (blood becomes more basic; ↑ serum pH) Hypertension Muscle weakness, fatigue, polyuria ↓ pH in intercalated cell ↓ pH in cells of proximal convoluted tubule ↑ loss of H+ through kidneys H+ secretion into cortical collecting duct ↑ H+ ATPase activity in intercalated cell Activation of glutaminase in proximal convoluted tubule HCO3- pumped into blood ↑ production of HCO3- (product of glutamine breakdown) ↑ breakdown of glutamine Hypokalemia (See Hypokalemia: Clinical Findings slide) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 16, 2020 on www.thecalgaryguide.com

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