potassium balance Flashcards
where is potassium found (food)?
leafy vegetables, most fruit/fruit juice and in potatoes, especially if they are fried or baked
is the concentration of potassium high inside cells or outside cells?
inside
ways in which we can lose potassium
urine, regulated by the kidneys - can be loss OR retention
stools and sweat - increase loss when there is intense hear/diarrhoea
what organ controls the day to day regulation of potassium levels?
kidneys
what substances cause potassium to shift into cells?
insulin, adrenaline and aldosterone
the way we gain potassium
diet
regulation of K+ homeostasis
Acute regulation:
Distribution of K+ through ICF and ECF compartments
Chronic regulation:
Achieved by the kidney adjusting K+ excretion & reabsorption
Potassium functions
- Determines ICF osmolality → cell volume
- Determines resting membrane potential → very important for normal functioning of excitable cells
(i. e. repolarisation of myocardial, skeletal muscle & nerve cells) - Affects vascular resistance
do intracellular concentrations of ions change?
intracellular concentrations of ions don’t change commonly, but the the extracellular concentration can and does change in certain clinical situations
where is 90% of body K located?
intracellularly
what maintains low Na+ and high K+ levels?
Na+-K+-ATPase pump
role of the sodium potassium pump?
uses the energy from hydrolysis of ATP to do following:
establish a net charge across the plasma membrane (salty banana, inside more negative)
the resting potential prepares nerve and muscle cells for the propagation of action potentials leading to nerve impulses and muscle contraction
accumulation of sodium ions outside of the cell draws water out of the cell and thus enables it to maintain osmotic balance (otherwise it would swell and burst from the inward diffusion of water)
after a meal what happens?
slight increase in plasma [K+], which is quickly shifted into ICF compartment
shift is mostly under hormonal control (Insulin, Adrenaline, Aldosterone, pH changes)
Hyperkalaemia
Hypokalaemia
plasma [K+] > 5.5mM
plasma [K+] < 3.5mM
how is a membrane potential formed?
the creation of ionic gradients
-an ionic gradient is the combination of an electrical and a chemical gradient
at rest, is the cell membrane more permeable to potassium or sodium?
potassium
how does hypokalaemia (low potassium outside the cell) affect the heart?
- makes the resting membrane potential more negative
- causes hyperpolarisation
-this means it will take even longer to reach the threshold than normal – which will delay firing off an AP, changing the rhythm of the heart (ECG changes)
how does hyperkalaemia (high potassium outside the cell) affect the heart?
increase the resting potential, making it less negative, so it approaches the threshold more quickly - firing off AP’s too quickly (ECG changes)
what is hypokalaemia caused by?
-renal or extra-renal loss of K+ -restricted intake of K+
eg.
- Long-standing use of diuretics w/out KCl compensation
- Hyperaldosteronism/Conn’s Syndrome (increased aldosterone secretion)
- Prolonged vomiting → Na+ loss → increased aldosterone secretion → K+ excretion in kidneys
- Profuse diarrhoea
what happens as a result of hypokalaemia?
↓release of adrenaline, aldosterone and insulin
what causes hyperkalaemia?
- acute hyperkalaemia can occur normally following prolonged exercise (released from skeletal muscle into ECF)
- insufficient renal excretion
- increased release from damaged body cells eg. during chemotherapy, long-lasting hunger or severe burns
- long-term use of potassium-sparing diuretics
when the plasma K+ concentration becomes greater than 7mM what happens?
asystolic cardiac arrest
a rise in plasma K+ stimulates what substance?
insulin - enhances uptake of K+ into cell, lowering plasma levels
what infusion can be used to help decrease plasma K+ levels?
Insulin/Glucose infusion used to drive K+ back into cells
-glucose is given with it to prevent hypoglycaemia (drop in blood glucose)
how do aldosterone and adrenaline affect K+ levels?
stimulate Na+-K+ pump and cellular K+ influx, lowering plasma K+ levels
what increases the RISK of hyperkalaemia?
drugs like β-blockers, ACE inhibitors etc. raise serum [K]
what increases the RISK of hypokalaemia?
loop diuretics (used to treat heart failure)
Na+ and K+ in the glomerulus
Na+ & K+ filtered freely at glomeruli
Plasma & GF have same [Na+] & [K+]
how much of the Na+ and K+ is reabsorbed in the GFR?
60-70%
Fraction that is reabsorbed in PCT is constant, although the absolute amount reabsorbed varies with GFR
K+ movement in PCT
look at slide 19 diagram for Na+ movement
in the PCT, K+ reabsorption is passive and paracellular through tight junctions
Na+/K+ ATPase pump on the basolateral side - acts to maintain high potassium levels within the kidney cells, so K+ will diffuse down the concentration gradient through channels in the basolateral membrane into the blood
Na+/K+ movement in LoH
look at slide 20 diagram
thin ascending limb get Na & Cl diffusing out
as move up into the thick ascending limb, active reabsorption/pumping of Na & Cl out of the fluid and water cannot follow, thereby making stuff in the tubule more and more dilute
this is done via a Na/2Cl/K symporter on the luminal membrane which is driven by the [Na] gradient from lumen-cell
K+ moves into the medullary interstitial fluid, contributing to the medullary osmotic gradient
over 90% of the K+ that is filtered out of the glomerulus goes where?
reabsorbed in PCT and LoH
which specific parts of the nephron are in control of the day to day variations of K+ excretion?
the principle cells of the late DCT and collecting duct
excretion of K+ –> how it works (slide 21 diagram)
So if we have excess K and want to excrete it out, K+ enters the secreting cells from the blood via the Na-K-ATPase pump.
It then diffuses from the cell down the electrochemical gradient through K channels that exist in the luminal/apical membrane into the tubular fluid.
The electrical gradient across the luminal membrane normally opposes the exit of K+ from the cell but that gradient is reduced by the Na flux through the EnaC channel in that membrane which is stimulated by aldosterone
This is mainly why K+ secretion is coupled with Na+ reabsorption, i.e., the more Na+ reabsorbed by the principle cell, the more K+ secreted
A K-Cl cotransporter (symporter) also exists in the apical membrane and transport both K and Cl from the cell into the lumen
EnaC channels can be…
inhibited
what determines the secretion of K+ into the DCT?
K+ intake
Changes in pH
-alkalosis will cause more secretion of K+/decrease in [serum K+], and acute acidosis will decrease secretion of pH as you want to retain more in the blood
what 3 things help cause a switch between K+ secretion and reabsorption?
1) activity of Na-K-ATPase pump
2) (altering the) electrochemical gradient
3) (altering the) permeability of luminal membrane channel
Aldosterone and K+ secretion
aldosterone increases the activity of the Na+/K+ pump, increasing K+ influx into the tubular lumen
this contributes to the cell - lumen concentration gradient
aldosterone also increases the activity of the ENaC channels, so Na+ reabsorption increases,
and the permeability of luminal membrane to K+ increases
how does increased plasma [K+] increase K+ secretion? (3 ways)
slows exit from basolateral membrane which increases the intracellular concentration of calcium
increased activity of the Na+/K+ pump which increases [K+] within the cell
aldosterone secretion is stimulated
alkalosis causes what?
an increase in the activity of the Na+/K+ pump
how does acidosis limit K+ excretion?
the increase in [H+] of ECF reduces activity of Na/K ATPase pump – this decreases intracellular [K+] so less is excreted
how does an increase in tubule fluid flow rate come about?
- ↑GFR
- Inhibition of re-absorption
- K-wasting diuretics
sweeps away secreted K
how does ADH affect potassium excretion?
stimulates K secretion
when there is severe hypokalaemia which cells become activated?
α-Intercalated Cells of late DCT/CD, which act to reabsorb K+
Potassium hydrogen ATPase pump that gets activated under this situation
A fall in ECFV leads to increased Na & fluid reabsorption in PCT, which should cause K secretion into urine to decrease, but it doesn’t - why not? slide 30
because, the reduction in ECFV stimulates aldosterone release which stimulates distal potassium secretion
as a result of K excretion remains relatively constant
what happens when someone is losing a lot of Na+, eg. when vomiting?
the change in Na+ will be picked up as a change in osmolality and detected by the macula densa, which interacts with the JGA and results in renin being released
Angiotensin II stimulates the adrenal cortex to release aldosterone – causes increase in sodium retention and increase in water
this reabsorption which restores BP, volume and sodium
however, we could then be in a situation where we are losing a lot of potassium, so to counteract that if potassium levels get too low we can activate intercalated cells to increase K+ retention.
Addison’s Disease
primary adrenal insufficiency
rare disease, adrenal glands produce insufficient steroid hormones
damage to cortex, leads to decreased hormone production (sex hormones, cortisol, aldosterone) leads to numerous symptoms
eg. deficiency in aldosterone means the body is secreting large amounts of Na, so low serum Na levels, body retaining K - hyperkalaemia
Treatment - corticosteroid replacement therapy for life
secondary adrenal insufficiency
much more common than Addisons disease
the pituitary gland fails to produce enough adrenocorticotropin (ACTH) - hormone that stimulates the adrenal glands to produce cortisol
low ACTH output = drop in cortisol production
adrenal glands shrink due to lack of ACTH stimulation
what is the primary cause of hyperaldosteronism?
Conns Syndrome
what happens in Conns syndrome?
excess release of aldosterone - released in the absence of stimulation by Angiotensin II
aldosterone stimulates kidneys to increase Na+ reabsorption and K+ excretion - causing hypertension
increase in fluid volume causing hypokalaemia, hypernatremia and alkalosis
