2012B10 Outline the mechanisms by which the kidney maintains potassium homeostasis.

· Intro

· Filtration

· Reabsorption

· Secretion

Normal values

· ECF 3.5-5mM (tight control required for cell function)

· ICF 150mM

· Intake 1-1.5mmol/kg/day

· Output: urine >> faeces, sweat

Renal potassium handling

· Freely filtered

· Fixed fraction reabsorbed (~95%)

· Variable secretion

· Small amount compulsory excretion (5%)

Significance

· Lower priority than sodium reabsorption

· Compulsory excretion means compulsory intake ~0.5mmol/kg/day

Freely filtered

· 180L/day x 4mM = 720mmol/day

Minimal variation

· Minimal variation in ECF concentration

· Minimal variation in GFR: autoregulation to 125mL/min

o Myogenic: ↓afferent arteriolar stretch -> reflex dilatation (effective for mAP 70-170mmHg)

o Chemical (tubuloglomular feedback): ↓NaCl at distal tubule -> reflex dilatation

o Hormonal (renin-angiotensin): ↓afferent arteriolar stretch or ↓NaCl at distal tubule -> ↑renin

Proximal tubule

(65%)

· Paracellular transit:

o Solvent drag

o Passive diffusion

Loop of Henle

(~20%)

· Secondary active transport (major)

· Passive paracellular diffusion (minor)

Collecting ducts

(~10%)

(alpha intercalated cell)

· Active transport

Location	· Principal cell of the connecting tubule and collecting duct
Mechanism	· Secondary active transport
Effect of aldosterone	· Stimuli for release: o CRH -> ACTH (necessary for synthesis; minor stimulus for release) o Angiotensin 2 (major) o Hyperkalaemia (minor) · Effect on principal cell o ↑Na⁺K⁺ATPase synthesis and activity o ↑ENaC and ROMK activity o i.e. ↑Na⁺ reabsorption at expense of ↑K⁺ secretion
Other physiology	Factors increasing K⁺ secretion: · ↑ECF [K⁺] (↑Na⁺K⁺ATPase activity independent of aldosterone) · ↑Urine or Na+ flow rate (e.g. glycosuria) · ↑Non-Cl^- anions
Drugs	· Loop diuretics: inhibit Na⁺K⁺2Cl^- symporter, hence ↑tubular flow, ↑K⁺ secretion · Thiazide: inhibit Na⁺Cl^- reabsorption in distal convoluted tubule -> ↑tubular flow, ↑K⁺ secretion · MR antagonist: ↓Na⁺K⁺ATPase synthesis and activity, ↓ROMK activity -> ↓K⁺ secretion
Pathology	· Renal failure: ↓GFR -> ↓tubular flow -> ↓K⁺ secretion -> risk hyperkalaemia