Control of K+ levels

Question 1

Where is K+ mostly found

Answer 1

Intracellularly

Normal concentration 3.5.-5.5mmol/l

Question 2

Effect of [K+] on the membrane potential

Answer 2

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.

Question 3

Effect of hypokalemia on ECG

Answer 3

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

Question 4

ECG changes seen in hyperkalemia

Answer 4

High T wave

prolonged PR interval/absent P waves

widened QRS complex

Question 5

Why is plasma [K+] not a good estimation of total body K+

Answer 5

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+

Question 6

Factors that alter K+ distribution in the body

Answer 6

Catecholamines
Insulin
Aldosterone
Acid-base balance
Plasma osmolality
Cell lysis
Exercise

Question 7

How do catecholamines alter K+ distribution

Answer 7

Catecholamines activate alpha and beta adrenergic receptors. Stimulation of alpha receptors releases K+ and stimulation of b2 receptors promotes K+ uptake by cells

Question 8

How does acid-base balance alter K+ distribution?

Answer 8

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

Question 9

How does an increase in plasma osmolality cause release of K+ ?

Answer 9

Increase plasma osmolality causes water to leave the cells. Cells shrink and [K+]i increases so K+ leaves the cells.

Question 10

Why can muscle damage lead to hyperkalemia?

Answer 10

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+

Question 11

What is the effect of insulin on serum K+ levels?

Answer 11

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

Question 12

State three things which cause increased plasma [K+]

Answer 12

Insulin deficiency (diabetes mellitus)

Metabolic acidosis

Increases plasma osmolality

Muscle damage (particularly crush injuries)

Strenuous exercise

Aldosterone deficiency (Addison’s)

Question 13

Factors that affect renal excretion of K+

Answer 13

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

Question 14

Describe the process of ion exchange in the cortical collecting duct

Answer 14

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.

Question 15

Name four factors that affect the regulation of K+ secretion from the CCD

Answer 15

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)

Question 16

How does hyperkalemia affect secretion of K+ in the CCD?

Answer 16

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

Question 17

How does aldosterone alter K+ secretion?

Answer 17

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

Question 18

Causes of hypokalemia

Answer 18

Metabolic alkalosis

Insulin excess

beta-adrenergic activity

GI problems: (diarrhoea, vomiting)

Hyperaldosteronism

Loop diuretics

Renal disease

Question 19

Treatment of hypokalemia

Answer 19

Change diet

Change/stop any diuretics

Infusion of K+ if necessary

Question 20

Causes of hyperkalemia

Answer 20

Metabolic acidosis

NSAIDs

Insulin deficiency

Haemolysis

Cell destruction/trauma

ACEi

Chronic renal failure (decreased excretion)

Question 21

Treatment of hyperkalemia

Answer 21

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

Question 22

How does acid-base balance affect K+ levels?

Answer 22

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

Question 23

How is K+ affected in acute acidosis?

Answer 23

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.

Question 24

How is K+ affected in chronic acidosis

Answer 24

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.

Question 25

How does vomiting affect K+ levels?

Answer 25

Prolonged vomiting causes metabolic alkalosis because there is a loss of gastric H+ from the stomach (and K+) while HCO3- is secreted into the blood.

Kidneys respond to this by increasing filtration of HCO3-. Some of the filtered load is reabsorbed in the PCT, while the rest binds to Na+ and passes to the DCT where it stimulates K+ and H+ secretion. (also causes Cl- depletion)

Reduction of extracellular fluid volume activates RAAS and K+ secretion.