Week 6 - Potassium control Flashcards
Why does small shifts of K result in such a big increase in ECF concentrations?
-The ECF is kept at such a low conc (approx 4.5mmol) that a shift of 1% of ICF results in a 50% rise in ECF
What maintains the difference between ECF and ICF?
-NaKATPase
What effect does K have on the resting membrane potential during normal, decreased ECF and increased ECF?
-K+ establishes a gradient across the cell membrane which sets up the RMP
normal -> steady RMP
decreased ->increases the gradient across the cell and hyperpolarises
increased -> decreases the gradient across the cell and depolarises
By what two mechanisms is potassium regulated?
-Internal and external balance
What is the purpose of internal balance?
-To have an immediate effect by shifting K between ECF and ICF -> does not solve the problem only helps cope with it
What is the function of external balance?
-To adjust renal K excretion to correct K imbalance
Describe the events which occur to deal with K after ingestion of a meal
1)Intestine and colon absorb dietary K -> large amount of K enters ECF
2)4/5ths of ingested K moved into cells within minutes
3)After a slight delay kidneys begin to excrete K and K is slowly released from cells
Excretion is complete within 6-12 hours.
By what mechanism is ECF shifted to ICF in internal balance?
-Mediated via NaKATPase
By what mechanism is K shifted from ICF to ECF in internal balance?
-Through ROMK
What are the three factors which increase K uptake by cells?
- Hormones
- Increased [K] in ECF
- Alkalosis
What hormones cause cellular uptake of K?
- Insulin
- Aldosterone
- Catecholamines
How does alkalosis cause cellular uptake of K?
-ECF K is exchanged for H+ in order to correct alkalosis
How do hormones promote cellular uptake of K?
-Increase NaKATPase activity
What factors influence K to be shifted out of cells?
- Exercise
- Cell Lysis
- Increased ECF osmolarity
- Low ECF [K]
- Acidosis
How does exercise promote K to be released from cells? How is this corrected?
- Skeletal muscle contraction releases K in proportion to intensity of exercise
- Surrounding non-contracting tissues uptake K and prevent hyperkalaemia
- Exercise also increases catecholamines to offset increase in ECF [K]
Give 3 examples of clinical conditions/treatments which cause cell lysis
- Rhabdomyolysis
- Intravascular haemolysis
- Cancer chemotherapy
How does increase in plasma osmolarity effect K?
- Water moves from ICF to ECF to decrease osmolarity
- Increases [K] in ICF so K leaves down conc gradient
Describe the renal handling of potassium
- K is freely filtered at the glomerulus
- Most reabsorbed in PCT and LoH
- Control occurs in DCT and CD where potassium secretion/absorbtion is altered to match ingestion
From which cells in the nephron is potassium secreted?
-Principal cells of DCT and cortical CD
Describe K secretion in principal cels off DCT/CD
- NaKATPase basolateral activity maintains high ICF [K]
- this creates a chemical gradient for secretion
- Na influx produces a high electrical gradient
- K leaves the cell down the electro-chemical gradient via apical K channels
How does [K] ECF effect K secretion by principle cell
-high [K] ECF stimulates NaKATPase, increases permeability of apical K channels and stimulates aldosterone
How does aldosterone affect K secretion by principle cells?
-Aldosterone increases expression of NaKATPase, K channels and ENaC thus increasing secretion
How does acid base status influence K secretion by principle cells?
- Acid base status -> acidosis decreases secretion via inhibition of NaKATPase and decreased K channel permeability
- > alkalosis increases secretion via stimulating NaKATPase and increasing K channel permeability
What luminal factors affect K secretion by principal cells?
- Increased DCT flow rate washes away luminal K -> Increased gradient = increased secretion
- Increased Na delivery to distal tubule -> more Na resorbed, more K secreted
Which cells of the DCT and CD resorb K?
-Intercalated cells
Describe K resorption by intercalated cells
-Active process mediated by H+K+ATPase in apical membrane
When is hyperkalaemia defined?
-[K]>5.0mmol/L
When can increased intake cause hyperkalaemia?
-When there is renal dysfunction
What can cause decreased renal excretion of potassium?
- Acute/chronic injury
- Drugs which block potassium excretion eg ACEI, K sparing diuretics
- Low aldosterone states eg addisons
How can diabetic ketoacidosis cause hyperkalaemia?
- No insulin ->Decreased internal balance shifting K from ECF to ICF
- Increased plasma osmolarity
- Metabolic acidosis
What are the clinical features of hyperkalaemia?
- Altered excitability of the heart -> arrhythmias or heart block
- Gastrointestinal neuromuscular dysfunction -> paralytic ileus
- Acidosis
How does hyperkalaemia cause arrhythmias?
-Increased ECF conc -> decreased gradient -> depolarisation of cardiac tissue -> more fast Na channels remain inactive -> heart less excitable
Describe the ECG changes seen in hyperkalaemia
- Tented T wave
- Prolonged PR interval
- Depressed ST
- Absent P wave
- Ventricular fibrillation
What is the emergency treatment of hyperkalaemia?
- IV calcium gluconate
- Glucose + insulin IV
- Nebulised Salbutamol
Describe long term treatment of hyperkalaemia
- Treat cause eg stop medications, treat DKA etc
- Reduce intake
- Measures to removes excess K -> dialysis, binding resins
When is hypokalaemia defined?
-[K] less than 3.5mmol/L
What problems with external balance can lead to hypokalaemia?
- Excessive GI loss via diarrhoea, bulimia, vomiting
- Renal loss via diuretic drugs, high aldosterone
What problems with internal balance can cause hypokalaemia?
- excess insulin, aldosterone and catecholamines
- low ICF
- Metabolic alkalosis
Describe the clinical features of hypokalaemia
- Arrthymias
- Paralytic ileus
- Muscle weakness
Why does hypokalaemia cause arrhythmias?
- Increased gradient between ICF and ECF
- Hyperpolarisation of cell
- More fast Na channels in active form
- Heart more excitable
What is the main ECG change in hypokalaemia?
-Low T wave
How do you treat hypokalaemia?
- Treat cause
- K replacement via IV/oral
- potassium sparing diuretics if due to increased aldosterone
Where is most of the bodys K?
-ICF (98%) mostly skeletal muscle
