Potassium Control Flashcards
What maintains the potassium concentrations?
3Na-2K-ATPase
Normal [K+] in ICF and ECF?
ICF = 120-150 mmol/L ECF = 3.5-5 mmol/L
Why is high potassium inside cells and mitochondria essential?
Maintains cell volume Regulates intracellular pH Controls cell-enzyme function DNA and protein synthesis Cell growth Low potassium outside cells is largely responsible for the membrane potential of excitable and non-excitable cells
How does hyper and hypokalaemia affect the membrane potential?
Hyperkalaemia: depolarises it
Hypokalaemia: hyperpolarises it
What can hypokalaemia cause?
Inability of kidney to form concentrated urine
Metabolic alkalosis
Enhancement of renal ammonium secretion
What can hyperkalaemia cause?
Cardiac arrhythmias
Where in the nephron is potassium reabsorbed?
PCT
Thick ascending limb
DCT
Cortical collecting duct
Where in the nephron is potassium secreted?
Distal tubule
Cortical collecting duct
Both by principal cells
What percentage of potassium is reabsorbed in the PCT and by what processes?
67%
Paracellular diffusion
What percentage of potassium is reabsorbed in the thick ascending limb and by what processes?
20%
Na-K-2Cl transporter in apical membrane
(Driven by Na-ATPase)
How much potassium is secreted in principal cells of the DCT and cortical CD?
15-20%
What percentage of potassium is reabsorbed by intercalated cells of the DCT and CD? By which transporter?
10-12%
Hydrogen-potassium transporter
Describe process of secretion of potassium
Na-K-ATPase on basolateral membrane increases intracellular K conc and decreases Na conc
High intracellular K creates gradient for potassium secretion
Na moves from lumen to cell via ENaC making lumen negatively charged
Favourable electrochemical gradient for K+ secretion via apical K+ channels
How does high ECF potassium concentration stimulate more potassium secretion?
Directly stimulates Na-K-ATPase and increases permeability of apical K+ channels
Also stimulates aldosterone secretion
How does aldosterone stimulate K secretion?
Increases transcription of Na-K-ATPase in basolateral membrane and ENaC/K+ channels in apical membrane
What luminal factors affect potassium secretion?
Increased distal tubular flow rate - washes away luminal K+, increasing K+ loss
Increased Na+ delivery to distal tubule - more sodium can the. Be absorbed so more potassium is lost
How does external balance control extracellular potassium concentration?
Adjusts renal potassium excretion to match intake - regulates total body content
Depends on dietary intake and excretion by GI and kidneys
Responsible for long term control
Slow acting - 6-12 hours to secrete a load
How does internal balance regulate potassium concentration?
Immediate effect
Shift potassium between extracellular fluid and intracellular fluid
-If ECF [K] increases - K+ into cells via Na-K-ATPase
-If ECF [K] decreases - K+ out of cells via ROMK
What are the main things that promote potassium uptake into cells?
Hormones
- insulin
- aldosterone
- catecholamines
Increased [K+] in ECF
Alkalosis (low ECF H+ concentration)
What are the general factors that promote potassium shift into ECF out of cells?
Low [K+] ECF Exercise Cell lysis Increased plasma/ECF osmolarity Acididosis
How does insulin promote uptake of potassium into cells (causing hypokalaemia)
K+ in splanchnic blood stimulates insulin secretion by pancreas
Insulin stimulates K+ uptake by muscle and liver via increase in Na-K-ATPase
How does aldosterone reduce ECF [K+]
K+ in blood stimulates aldosterone secretion
Stimulates Na-K-ATPase
Stimulates K+ secretion in kidneys
How do catecholamines reduce [K+] in ECF?
Act via β2 adrenoreceptors
Stimulate Na-K-ATPase
How does alkalosis cause hypokalaemia?
H+ excreted from cells to correct alkalosis
Get reciprocal K+ shift into cells because the inside becomes electronegative
How does exercise increase ECF potassium conc?
Skeletal muscle contraction causes net release of potassium during recovery phase of action potential so K+ exits cells
Skeletal muscle damage also releases K+
How is hyperkalaemia prevented in exercise?
Uptake of potassium by non-contacting tissues
Release of catecholamines
How can cessation of exercise lead to hypokalaemia?
Non-respiring tissues still taking up potassium
Can drop to <3mmol
Cause sudden death
What can cause cell lysis and release of potassium into ECF?
Trauma in skeletal muscle causing muscle fell necrosis
Intravascular haemolysis due to eg incompatible blood transfusion or G6PD deficiency
Chemotherapy - release of potassium from tumour cell lysis
Why can diabetics become hyperkalaemic?
If they go into diabetic ketoacidosis
Increase in plasma and ECF toxicity causes water to move from ICF to ECF
Increases [K+] in cells so K+ leaves down conc gradient
Also acidosis causes increased uptake of H+ increased loss of K+ from cells.
Can hypokalaemia cause acidosis or alkalosis?
Alkalosis
How does hypokalaemia cause cardiac arrhythmias?
Hyperpolarises cardiac cells
More fast Na+ channels available in active form
Heart more excitable
Causes of hypokalaemia?
Alkalosis Inadequate intake Excessive loss -vomiting -diarrhoea -diuretics -osmotic diuresis (diabetes) -high aldosterone
Clinical features of hypokalaemia?
Heart and neuromuscular dysfunction
- paralytic ileus
- muscle weakened
- dysfunction of CD cells - unresponsive to ADH - nephrogenic diabetes
Treatment of hypokalaemia?
Treat cause
K+ replacement (IV/oral)
If due to high aldosterone - K+ sparing diuretics blocking action of aldosterone on principal cells eg Amiloride
Aldosterone antagonist - spironolactone
How does hyperkalaemia cause heart arrhythmias?
Depolarises cardiac cells
More fast Na+ channels inactive
Heart less excitable
Causes of hyperkalaemia?
Inadequate renal excretion Acute/chronic kidney injury Reduced mineralocorticoid effect K+ sparing diuretics ACE inhibitors Adrenal insufficiency Acidaemia Cell lysis K+ shift
Clinical features of hyperkalaemia?
Heart and neuromuscular dysfunction
- paralytic ileus
- acidosis
Treatment of hyperkalaemia?
Emergency
- Ca2+ gluconate to reduce effect on heart
- IV insulin and glucose
- dialysis to remove excess K+
Long term
- dialysis
- oral potassium binding resins - bind in the gut
- reduce intake
- treat cause