Potassium Regulation Flashcards
What is the consequence of changes in potassium on the cell membrane resting potential?
Increased [K+]ECF -> reduces gradient -> depolarises cell (less negative)
Decreased [K+]ECF -> increases gradient -> hyperpolarises cell (more negative)
What is the difference in [K+] in the ICF & ECF? Why is this significant?
98% of K+ in ICF, 2% in ECF
Intracellular > interstitial = plasma
(interstitial fluid & plasma separated by potassium permeable wall)
Difference maintained by Na+/K+-ATPase (K+ gradient creates the resting membrane potential)
Only a shift of 1% K+ between the ICF & ECF would raise the [K+]ECF by 50%
How is potassium regulated?
5%-10% lost via GI tract, rest absorbed
EXTERNAL: (slow)
Adjust renal excretion of K+ to match intake of K+ (by controlling K+ secretion)
Controls total body K+ content over the long term
INTERNAL:
Shifts K+ between the ECF and ICF (via ROMK & H+/K+ antiporter, controlled by Na+/K+-ATPase)
ROMK stimulated by:
- reduced [K+]ECF
- exercise
- cell lysis (K+ leaks out)
- increase in ECF osmolarity
- reduced pH of ECF (shift of H+ into cells, reciprocal K+ shift out of cell -> inhibits H+/K+ antiporter)
Na+/K+ATPase stimulated by:
- insulin, aldosterone, catecholamines
- increased [K+]ECF
- reduced [K+]ICF (H+ moves out of cell to correct alkalosis, causing reciprocal K+ shift into cell via H+/K+ antiporter)
What factors promote K+ uptake into cells?
Insulin = K+ in splenic artery stimulates insulin secretion by the pancreas, increases activity of Na+/K+-ATPase to stimulate K+ uptake (liver & muscle cells)
Therefore treat hyperkalaemia by giving IV insulin
Aldosterone = stimulates Na+/K+-ATPase
Catecholamines = act on beta-2-adrenoceptors to stimulate Na+/K+-ATPase (note: effect of nebulised salbutamol)
What factors promote K+ shift out of cell?
Exercise = skeletal muscle contraction causes net release of K+ during recovery phase of AP (amount released directly proportional to intensity of exercise)
note: during exercise, the increased catecholamine secretion offsets the release of K+ by increasing K+ uptake
Cell lysis = releases K+ e.g. rhabdomyolysis, intravascular haemolysis (RBCs break down outside spleen) due to incompatible blood transfusion/G6PDH deficiency + primaquine, tumour cell lysis (chemotherapy)
Increased plasma tonicity = water moves from cells into ECF -> relative increase in [K+]ICF -> K+ leaves cell down conc. gradient
Where in the kidney is K+ reabsorbed & secreted?
Reabsorbed: PCT, thick ascending limb, DCT & collecting duct (intercalated cells)
K+ reabsorbed via H+/K+ antiporter (requires ATP)
Secreted: DCT & cortical collecting duct (principal cells)
Na+ movement into cell via ENaC depolarises cell (electrical gradient for K+ secretion) & high [K+]ICF (chemical gradient for K+ secretion)
note: increased DCT flow rate -> luminal K+ washes away & more Na+ delivered to cell -> increased K+ secreted
Increased pH & aldosterone stimulate K+ exporter
Aldosterone stimulates ENaC
Increased [K+]ECF, increased pH, & aldosterone stimulate Na+/K+-ATPase
What can cause hyperkalaemia?
External balance:
Increased K+ intake + renal dysfunction (unless K+ was given IV or inadequately excreted)
e.g. acute/chronic kidney disease, reduced aldosterone (caused by: adrenal insufficiency e.g. Addison’s disease, drugs reducing/blocking action of aldosterone, K+ sparing diuretics, ACE inhibitors)
Internal balance: Diabetic ketoacidosis (reduced insulin causes K+ shift into cells, metabolic acidosis, & hyperosmolarity of plasma) Metabolic acidosis Cell lysis Exercise
What are the clinical features of hyperkalaemia? How does this relate to the membrane potential?
Membrane resting potential: depolarised cardiac tissue -> more fast Na+ channels remain inactive (initially heart more excitable) -> heart less excitable (hyperpolarisation does not occur)
Heart = arrhythmias, heart block
GI = paralytic ileus (abdominal distension & reduced bowel sounds)
Acidosis
ECG: reduced rate of conduction (prolonged PR interval, depressed ST, P wave absent, VF)
Treatment:
EMERGENCY = IV calcium gluconate (stabilises membrane of cardiac cells -> reduces depolarisation) + IV insulin + glucose
OR salbutamol
+ dialysis (if required)
Longterm: dialysis + oral K+ binding resins (prevents reabsorption)
What can cause hypokalaemia?
External: excessive loss of K+ e.g. diarrhoea/vomiting, diabetes, diuretics, increased aldosterone (Conn’s syndrome - adrenal adenoma)
note: inadequate K+ unlikely; only caused by malnourishment/anorexia nervosa
Internal: metabolic alkalosis
What are the clinical features of hypokalemia? How does this relate to the membrane potential?
Membrane potential: cardiac tissue hyperpolarised -> more fast Na+ channels available in active form -> heart more excitable
(initial decrease in excitability as more stimulation is required to reach threshold)
Heart = palpitations (extra systoles) —> arrhythmias
GI = constipation, reduced bowel sounds (paralytic ileus)
Skeletal muscle weakness
Renal = nephrogenic diabetes insipidus (collecting duct insensitive to ADH)
ECG: low T wave, high U wave
Treatment: IV/oral K+ replacement
note: if due to increased mineralocorticoids, K+ sparing diuretics given to block action of aldosterone)
What are the three critical substances lost from the body from vomiting?
Electrolytes: sodium, chloride, some potassium (but not enough for hypokalaemia)
Water —> dehydration (more difficult to excrete bicarbonate: kidney attempts to reabsorb water by limiting secretion of electrolytes, including bicarbonate —> metabolic alkalosis)
H+ —> metabolic alkalosis (H+ also moves into ECF to reduce alkalosis, driving K+ into cells —> hypokalaemia)
What drugs affect potassium levels in the blood?
ACE inhibitors (reduce aldosterone secretion —> K+ retained —> hyperkalaemia)
Laxatives (high intestinal fluid content —> K+ in intestine relatively dilute —> more K+ lost from cells)
Diuretics
How is potassium involved in heavy exercise?
Mechanically ruptured RBCs release K+
ATP depleted —> ATP sensitive K+ channels unblocked —> K+ leaks out of cells
K+ ions act as vasodilators —> increases blood flow to exercising muscle
What is Liddle’s syndrome? What symptoms does this cause and why?
Hyperconductivity of sodium ion channels in DCT
Hypertension: systemic sodium overload —> increase in ECF volume
Hyporeninaemia: chronic hypertension —> down-regulation of RAAS
Hypokalaemia: excessive depolarisation of luminal membrane —> increased potassium leakage
Metabolic acidosis: increased availability of H+ for secretion (due to equilibrium shift to the left)
