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

 

List:

        Intro

        Filtration

        Reabsorption

        Secretion

 

Intro:

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

 

Filtration:

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

 

Reabsorption:

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

 

Secretion:

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

 

Recommended reading: https://cjasn.asnjournals.org/content/10/6/1050.full