Hyperkalemia (↓ Renal Excretion): Pathophysiology
Non-steroidal anti- inflammatory drugs (NSAIDs)
Inhibition of prostaglandins which promote renin secretion (see NSAIDs and the Kidney: Mechanism of Action and Side Effects slide)
Diabetic Nephropathy
Acute (AIN)and chronic (CIN) interstitial nephritis
Immune-mediated damage of the kidney tubule and interstitium
Damage to distal tubule leads to aldosterone resistance at principal cell
Aldosterone cannot ↑ EnaC insertion on principal cell of CCD
Epithelial sodium channel (ENaC) blockers
Acute kidney injury and chronic kidney disease
↓ Effective arterial blood volume (volume of blood effectively perfusing tissue)
↓ Oxygen perfusion to renal tissue causing renal ischemia
Autonomic neuropathy ↓ sympathetic drive to produce renin
Chronic juxtaglomerular cell damage ↓ synthesis of renin
Blockage of ENaC on the principal cells of the CCD
Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs)
Angiotensin II is either not formed (ACEi), or blocked at its receptor (ARBs)
Angiotensin II cannot stimulate the release of aldosterone from the adrenal cortex
Adrenal Insufficiency
Adrenal gland cannot produce sufficient amounts of aldosterone
↓ Renin secretion by the afferent arteriole prevents RAAS activation
↓ Aldosterone release from adrenal cortex
↓ ENaC (Na+ reabsorption channel) expression on principal cells of the cortical collecting duct (CCD)
Damage to kidney causes renal impairment and ↓ glomerular filtration rate
↓ Glomerular filtrate production means ↓ tubular flow rate
↓ Na+ delivery to the distal tubule
↓ Na+ reabsorption by ENaCs at the principal cell in CCD
↓ Na+ and water reabsorption by ENaCs in CCD ↓ Effective arterial blood volume (EABV)
Activates renin-angiotensin-aldosterone system (RAAS) leads to ↑ renin secretion in the afferent arteriole (see Physiology of the renin-angiotensin-aldosterone system (RAAS) slide)
↑ Na+ and water loss in tubular lumen
↑ Positive charge in tubular lumen
↓ Electronegativity gradient in tubular lumen
of CCD
↓ K+ excretion by the principal cell in the CCD as there is less of a electronegative gradient
↑ Accumulation of K+ in blood Hyperkalemia
Serum [K+] > 5.1 mmol/L
See Hyperkalemia: Clinical Findings slide
In the case of diabetic nephropathy and NSAIDS ↓ EABV does not stimulate RAAS and therefore aldosterone production
↓ Renin
↓ Aldosterone
↑ Renin secretion activates an ↑ in aldosterone production but aldosterone action at the principal cell is blocked because of ENaCs or resistance in AIN and CIN
↑ Renin
↑ Aldosterone
In the case of ACEi, ARBs, or adrenal insufficiency ↑ renin secretion does not lead to ↑ aldosterone
↑ Renin
↓ Aldosterone
Note: as described in the above flow chart, measuring serum renin and aldosterone levels can be used to help diagnose the cause of hyperkalemia.
Authors: Mannat Dhillon, Joshua Low, Emily Wildman, Huneza Nadeem Reviewers: Andrea Kuczynski, Marissa (Ran) Zhang, Adam Bass*, Kevin McLaughlin* * MD at time of publication
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published Aug 2, 2022 on www.thecalgaryguide.com