Control of K+ levels Flashcards
Where is K+ mostly found
Intracellularly
Normal concentration 3.5.-5.5mmol/l
Effect of [K+] on the membrane potential
K+ contributes -91mV to the membrane potential (nernst) and is therefore the major determinant of the resting potential
Low K+ levels makes the membrane potential more negative. Causes reduced excitability and muscle weakness.
High K+ levels move the resting potential closer to threshold, which can result in increased firing. High K+ causes cardiac arrhythmias and VF.
Effect of hypokalemia on ECG
As K+ moves out of the cell during repolarisation, ST wave is seen.
Low K+ can result in low T wave, high U wave, low ST segment
ECG changes seen in hyperkalemia
High T wave
prolonged PR interval/absent P waves
widened QRS complex
Why is plasma [K+] not a good estimation of total body K+
The majority of K+ in the body is intracellular. K+ readily moves in and out of cells in order to keep plasma concentration within the normal range.
Therefore a person may have low intracellular K+ stores but have a normal serum K+
Factors that alter K+ distribution in the body
Catecholamines
Insulin
Aldosterone
Acid-base balance
Plasma osmolality
Cell lysis
Exercise
How do catecholamines alter K+ distribution
Catecholamines activate alpha and beta adrenergic receptors. Stimulation of alpha receptors releases K+ and stimulation of b2 receptors promotes K+ uptake by cells
How does acid-base balance alter K+ distribution?
Metabolic acidosis increases plasma [K+] because the increase in [H+] causes H+ to move into the cell to balance the concentration gradient. K+ then moves out of the cell to balance the charge across the membrane.
Reverse for metabolic alkalosis
How does an increase in plasma osmolality cause release of K+ ?
Increase plasma osmolality causes water to leave the cells. Cells shrink and [K+]i increases so K+ leaves the cells.
Why can muscle damage lead to hyperkalemia?
Skeletal muscles constitute the largest fraction of cell mass in the body and contain 2/3 of the body’s K+. Abnormal leakage of K+ from muscle cells can lead to serious hyperkalemia.
Na/K-ATPase pumps K+ into cells. If this is inhibited as a result of tissue hypoxia hyperkalemia may result.
Tissue trauma, infection, haemolysis and extreme exercise also release K+ from cells and can cause high K+
What is the effect of insulin on serum K+ levels?
Insulin promotes the uptake of K+ by skeletal muscles and the liver by stimulating Na/K-ATPase.
High plasma K+ stimulates the release of insuln.
Rise in plasma K+ following a meal is greated in patients with diabetes mellitus. Insulin/dextrose infusions are used in emergencies for the treatment of hyperkalemia
State three things which cause increased plasma [K+]
Insulin deficiency (diabetes mellitus)
Metabolic acidosis
Increases plasma osmolality
Muscle damage (particularly crush injuries)
Strenuous exercise
Aldosterone deficiency (Addison’s)
Factors that affect renal excretion of K+
Plasma [K+]: increases levels increase secretion of aldosterone and uptake of K+ by the collecting duct.
Tubular flow rate: washes K+ away from secreting cells and maintains a concentration gradient
Secretion into the tubule
ADH: Na+ reabsorption favours secretion and excretion of K+
Aldosterone: increases K+ secretion
Describe the process of ion exchange in the cortical collecting duct
CCD is the primary site for K+ secretion. This is carried out by principal cells which actively take up K+ via a Na/K-ATPase on the basolateral membrane. K+ then diffuses out of the cell, down its concentration gradient into the lumen via K+ channels.
Intercalated A cells remove K+ ions from the interstitial tissue into the lumen by secreting H+ in exchange for K+ ions. Carbonic acid dissociates into HCO3- and H+ ions. H+/K+ATPase pumps H+ into the lumen and K+ into the cell. K+ ions diffuse out into the interstitium.
Name four factors that affect the regulation of K+ secretion from the CCD
Electrochemical gradient between the cells and lumen (controls the driving force of K+ across the luminal membrane)
Changes in permeability of the apical membrane to K+
Activity of the Na?K-ATPase (greater the pump activity, greter the secretion. Increased amounts of Na+ in the CCD lumen e.g. patients on diuretics, results in increased activity)
How does hyperkalemia affect secretion of K+ in the CCD?
Stimulate Na+K+-ATPase (increased uptake basolateral membrane, increased [K+]i, electrochemical gradient leading to K+ secretion.
permeability apical membrane to K+ increased
Stimulates aldosterone secretion
Increased tubular flow rate
How does aldosterone alter K+ secretion?
Aldosterone activates and increases the numbers of Na+ and K+ channels.
Na+ entry into the collecting duct is via diffusion through the ENaC channel. Entry of Na+ through this channel is increased by aldosterone. Aldosterone activates serum and glucocorticoid induced kinase (SGK) which increases Na+ and K+ transport.
Aldosterone also increases activity of the Na/K-ATPase
Na+ is reabsorbed, K+ is secreted into the urine
Causes of hypokalemia
Metabolic alkalosis
Insulin excess
beta-adrenergic activity
GI problems: (diarrhoea, vomiting)
Hyperaldosteronism
Loop diuretics
Renal disease
Treatment of hypokalemia
Change diet
Change/stop any diuretics
Infusion of K+ if necessary
Causes of hyperkalemia
Metabolic acidosis
NSAIDs
Insulin deficiency
Haemolysis
Cell destruction/trauma
ACEi
Chronic renal failure (decreased excretion)
Treatment of hyperkalemia
Immediate: calcium gluconate IV (decrease excitability muscles)
Short term (redistribution): insulin/dextrose (encourage uptake into cells) Na bicarb IV - corrects acidosis (forces K+ into cells) (induces metabolic alkalosis, but Na will increase fluid load)
Long term (K+ removal):
Loop diuretics
Cation exchange resins (Ca resonium) to hold K+ in stomach
Dialysis
How does acid-base balance affect K+ levels?
pH changes:
acidic: H+ enters the cell and K+ leaves the cell (hyperkalemia)
alkaline: H+ leaves the cell and K+ enters (hypokalemia)
K+ is transported with HCO3- to maintain electroneutrality. Therefore in acidosis where HCO3- in the ECF is low, both ions leave the cells, causing hyperkaemia. In alkalosis where HCO3- is high, both ions enter the cell, causing hypokalemia
How is K+ affected in acute acidosis?
Acute acidosis occurs over mins-hrs and causes reduced K+ secretion leading to hyperkalemia.
There is increased H+ secretion, and so K+ secretion falls. Permeability of the apical membrane is reduced because K+ channels are blocked by H+. High [H+] also inhibits the Na/K-ATPase, intracellular K+ concentration falls so there is less of a concentration gradient.
Chronic acidosis causes an increase in K+ excretion.
How is K+ affected in chronic acidosis
Chronic acidosis occurs over several days and leads to increased K+ excretion.
H+/K+ exchangers in skeletal muscle have increased activity so H+ is taken into cells and plasma [K+] increases. This stimulates the release of aldosterone.
Aldosterone acts on the DCT and principal cells of the CCD to increase permeability of the apical membrane to K+ and increase activity of the Na+/K+ATPase. The K+ gradient at the apical membrane increases so more K+ is secreted into the tubules and excreted from the kidneys.
Acidosis also causes decreased NaCl and water absorption from the PCT which increases tubular flow rate and decreases ECV. These also contribute to increased excretion by the same mechanism.
