Potassium balance Flashcards
What is our daily intake of potassium?
A typical daily intake in the UK is 50-125mmol.
Where do we obtain potassium from?
- Potassium is found particularly in leafy vegetables and most fruit and fruit juice, and in potatoes, especially if they are fried* or baked.
- high salt content
Describe potassium homeostasis
On image
What does regulation of potassium homeostasis imply?
Acute regulation:
- Distribution of K+ through ICF and ECF compartments
Chronic regulation:
- Achieved by the kidney adjusting K+ excretion & reabsorption
How does a sodium-potassium pump work?
On image
When does ECF pool change?
ECF pool will change more dramatically with changes in body K distribution e.g. after a meal, get slight increase in plasma [K+], which is shifted into ICF compartment
When does internal balance and acute regulation shift?
Shift mainly subject to hormonal control: Insulin Adrenaline Aldosterone pH changes
Define Hyperkalaemia and Hypokalaemia
Hyperkalaemia = plasma [K+] > 5.5mM
Hypokalaemia = plasma [K+] < 3.5mM
What creates a resting membrane potential?
Ionic gradients (i.e. combination of chemical & electrical gradients)
What does the Nerst equation determine?
Resting membrane potential of the ions (potassium and sodium)
These ions determine resting membrane potential
What happens when plasma [K+] is altered above or below normal (its effect on the membrane potential)
Normal: [K]o=3.5mM and [K]i=140mM ⇒ EK = -98.5
Hyperkalemia: [K]o=7mM and [K]i=140mM ⇒ EK = -80
Hypokalemia: [K]o=1.5mM and [K]i=140mM ⇒ EK = -121.5
What can changes in potassium cause?
Can severely affect the heart - cardiac cell membrane potential (depolarisations/hyperporlarisations) producing characteristic changes in ECG
What is cell membrane hyperpolarisation and depolarisation?
Cell membrane hyperpolarization – increased negativity of voltage across membrane, hence decreased excitability of neurones & muscle cells
Cell membrane depolarization – decreased negativity of voltage, hence threshold approached quicker, increased excitability & muscle contractions
What effect does Hyperkalaemia and Hypokalaemia have on the ECG?
Hyperkalaemia: ↑QRS complex, ↑amplitude T-wave, eventual loss P-wave
Hypokalaemia: ↓amplitude T-wave, prolong Q-U interval, prolong P-wave
When can Hypokalaemia caused by renal or extra-renal loss of K+ or by restricted intake occur and cause?
Long-standing use of diuretics w/out KCl compensation Hyperaldosteronism/Conn’s Syndrome (increases aldosterone secretion) Prolonged vomiting → Na+ loss → aldosterone secretion → K+ excretion in kidneys Profuse diarrhoea (diarrhoea fluid contains 50mM K+)
What does Hypokalaemia result in?
Hypokalaemia results in ↓release of adrenaline, aldosterone & insulin
When does acute hyperkalaemia normally occur?
Acute hyperkalaemia normal following prolonged exercise → normal kidneys excrete K+ easily
What disease states can occur as a result of Hyperkalaemia?
Insufficient renal excretion
Increased release from damaged body cells eg. during chemotherapy, long-lasting hunger, prolonged exercise or severe burns
Long-term use of Potassium-sparing diuretics
Addison’s disease (adrenal insufficiency)
When plasma concentration of potassium is greater than 7mM what can it cause?
asystolic - > cardiac arrest
How does insulin and glucose drive potassium back into cells?
Insulin extremely important – mechanism unclear, may stimulate Na-K-ATPase. Why is glucose given with it?
What other hormones stimulate the Na+-K+ pump?
Other hormones (aldosterone, adrenaline) stimulate Na+-K+ pump -> cellular K+ influx
What is external balance of potassium maintained by?
The kidney
How is potassium involved in the treatment of CVD?
Drugs like β-blockers, ACE inhibitors etc raise serum [K] →risk of hyperkalaemia
Conversely loop diuretics, used to treat heart failure, enhance risk of hypokalaemia
K+ excretion in the stools is not under regulatory control ⇒large amounts can be lost by extra-renal routes
What is the concentration of soidum and potassium in the BC
On image
What percentage of Na/+K+ is reabsorbed in the PCT?
60-70%
Fraction that is reabsorbed in PCT is ~ constant
Although absolute amount reabsorbed varies with GFR
Describe potassium movement on PCT
What happens if this Na+/ K+ pump is inhibited by dopamine?
- Potassium diffuses from the sodium-potassium pump from the epithelial cell into the capillaries
- Also passive across by passive and paracellular mechanisms (K+, Cl-, Na+)
If this is inhibited (by for eg dopamine, digitalis) then the Na gradient is dissipated, eventually loose primary Na transport and the associated secondary active solute transport and also NO osmotic gradient for water transport.
What determines K+ secretion in DCT?
How is this achieved?
- Increased K+ intake
- Changes in blood pH
- Alkalosis ⇒ ↑excretion of K+ ⇒ ↓serum [K+]
- *Acute Acidosis ⇒ ↓excretion of K+ ⇒ ↑serum [K+] - activity of Na-K-ATPase pump
- electrochemical gradient
- permeability of luminal membrane channel
What does aldosterone do?
Aldosterone is major regulator of K balance in the body. It acts to:
↑activity of Na+/K+ pump -> ↑K+ influx -> ↑[K+]i -> cell-lumen concentration gradient
↑ENaC channels -> ↑Na+ reabsorption -> ↓cell negativity and ↑lumen negativity -> voltage gradient
Redistributes ENaC from intracellular localization to membrane
↑permeability of luminal membrane to K+
On image
How does an ↑Plasma [K] increases K secretion?
slows exit from basolateral membrane -> ↑[K+]i -> cell-lumen concentration gradient
↑activity of Na+/K+ ATPase -> ↑[K+] within cell
↑Plasma [K] -> stimulates aldosterone secretion
On image
Describe the pathway that leads to an increase in potassium excretion
On image
How does alkalosis and acidosis effect secretion of potassium ions?
On image
What other factors can cause an increase in potassium excretion?
↑Flow rate by:
↑GFR
Inhibition of re-absorption
K-wasting diuretics
How are alpha-intercalated cells of late DCT/ CD involved in severe hypokalemia?
- Activation of potassium-hydrogen ATPase increases reabsorption into peritubular capillary
Dependence of potassium secretion on sodium and flow poses problems
WHY?
Changing effects of sodium or potassium may have unwanted effects on one of these but wanted effects on the other
How does a decrease in ECFV cause secretion/ excretion of potassium ions?
On image
Describe the RAAS cascade
On image
What factors shift K+ into cells and what factors shift potassium out of cells?
On table
Describe addisons disease
What does the cortex produce?
What can damage to the cortex cause?
What does a deficiency in aldosterone cause?
What treatment option is available for people with Addison’s disease?
Cortex produces: glucocorticoid hormones (e.g. Cortisol) Mineralocorticoid hormones (e.g. Aldosterone) Sex hormones (androgens & estrogens)
Primary Adrenal Insufficiency aka Addison’s disease (very rare ) as opposed to secondary adrenal insufficiency
Damage to cortex -> ↓↓ hormone production -> numerous symptoms
Deficiency in aldosterone ->
body secreting large amounts Na ->
low serum Na levels
body retaining K-> hyperkalaemia
Treatment usually involves corticosteroid (steroid) replacement therapy for life.
What does secondary adrenal insufficiency cause?
Pituitary ACTH -> Cortisol Decrease-> Adrenal glands shrink
What causes Primary Aldosteronism aka Conn’s Syndrome?
What does it cause?
Primary Aldosteronism aka Conn’s Syndrome
due to aldosterone-producing adenoma of ZG of adrenal gland
usually <3cm, unilateral & renin-unresponsive
Hyperaldosteronism (excess release of aldosterone) due to variety chronic disease
Most common (50-60%) due to Conn’s syndrome, remaining 40-50% due to bilateral adrenal hyperplasia Aldosterone release in absence of stimulation by Angiotensin II
↑↑↑ Plasma Aldosterone -> kidneys to stimulate Na+ reabsorption & K+ excretion -> develop hypertension* -> ↑fluid volume -> hypokalaemia (↓[K+]), hypernatremia and alkalosis
*↑bp & Na delivery to macula densa -> ↓↓release of renin -> renin-independent cause of hypertension (very difficult to control)
Treatment:
surgical removal of tumour-containing adrenal gland
hypertension & hypokalaemia controlled with K+-sparing agents e.g spironolactone
