45) Potassium Balance

Question 1

Where are the potassium ions found within the body?

Answer 1

• They are either found intracellularly (in cells) or extracellularly (outside of cells)
• A vast majority of K+ is found intracellularly
• Some cells have higher [K+] than others

Question 2

How are K+ balanced between the two stores?

Answer 2

• There is an internal balance between intracellular and extracellular K+ which is under the control of factors such as insulin, adrenaline, pH or aldosterone
• There is an external balance between intracellular and extracellular K+ which consists of a balance between the input and output of K+

Question 3

How can we influence the amount of K+ in the body?

Answer 3

• We take in K+ through our diet

- We give out K+ through urine, stools (faeces) and sweat

Question 4

What are the different regulation of K+?

Answer 4

• Acute/short term: Distribution of K+ between intracellular and extracellular fluid compartments (i.e. the internal K+ balance)
• Chronic/long term: Achieved by adjusting K+ excretion and absorption (i.e. the output part of the external K+ balance)

Question 5

What is the function of K+?

Answer 5

• It determines the intracellular fluid osmolality which impacts the volume of the cell
• It determines the resting membrane potential which is very important for the functioning of excitable cells (those that deal with electrophysiology, e.g. heart muscle cells and neurones)
• It affects vascular resistance and blood flow

Question 6

How is the difference in intracellular and extracellular K+ concentrations maintained?

Answer 6

• This is done mainly through the Na+/K+ ATPase (Na+/K+ pump)
• The pump utilises the hydrolysis of ATP to ADP and inorganic phosphate to pull K+ into the cell and expel Na+ from the cell
• This is the reason where this is a high [K+] located intracellularly and only a tiny amount is found in extracellular fluid (ECF)

Question 7

How is a slight change in plasma [K+] dealt with when regulating K+ distribution?

Answer 7

• When there is slight increase in plasma [K+] (e.g. after a meal), the extra K+ is shifted into the Intracellular Fluid (ICF) compartment
• The change in balance is regulated and controlled by hormones such as insulin, adrenaline, aldosterone and blood pH changes

Question 8

What are deficiencies in K+ concentration called?

Answer 8

• Hyperkalaemia: When plasma [K+] is higher than normal

- Hypokalaemia: When plasma [K+] is lower than normal

Question 9

What is the resting membrane potential?

Answer 9

• Membrane potentials are created when a plasma membrane acts as a barrier which creates an ionic gradient (i.e. a combination of chemical and electrical gradients)
• The resting potential difference is a ratio of the extracellular and intracellular [K+]
• The normal resting membrane potential is maintained by the dynamic balance between Na+ and K+ concentrations

Question 10

Why are small changes in plasma [K+] dangerous?

Answer 10

• Small changes in plasma [K+] can cause the membrane potential in all excitable cells to be altered
• This has severe effects on cardiomyocyte membrane potential affecting their function.
• These changes also produce characteristic changes in ECG

Question 11

What changes are seen in an ECG when a patient suffers from hyperkalaemia and hypokalaemia?

Answer 11

• Hypokalaemia: Decreased amplitude of T-wave, prolonged Q-U interval and prolonged P-wave
• Hyperkalaemia: Increased QRS complex, increased amplitude of T-wave and eventual loss of P-wave

Question 12

What is the threshold potential?

Answer 12

• The membrane potential which a cell must surpass in order for the cell to fire an action potential

Question 13

How are excitable cells affected by hypokalaemia and hyperkalaemia?

Answer 13

• In hypokalaemia the cells are more hyperpolarised. This means they have a more negative resting potential causing them to be less excitable
• In hyperkalaemia the cells are more depolarised. This means they have a more positive resting potential causing them to be more excitable

Question 14

How is hypokalaemia caused?

Answer 14

• It is caused by extra-renal loss of K+ or by restricted intake. This can be due to:
• Extended use of diuretics without KCl compensation
• Hyperaldosteronism (increased secretion of aldosterone)
• Prolonged vomiting leading to increased Na+ loss causing increased aldosterone secretion and hence causing K+ to be excreted by the kidney
• Profuse diarrhoea

Question 15

What does hypokalaemia cause?

Answer 15

• Decreased resting potential

- Decreased release of adrenaline, aldosterone and insulin

Question 16

How is hyperkalaemia caused?

Answer 16

• Acute hyperkalaemia is normal during prolonged exercise
• It can be caused by disease states. This includes:
• Insufficient renal excretion
• Increased release from damaged body cells (e.g. during chemotherapy)
• Long-term use of potassium-sparing diuretics
• Addison’s disease

Question 17

What can hyperkalaemia cause?

Answer 17

• It can be life threatening as it causes asystolic cardiac arrest

Question 18

How is hyperkalaemia treated?

Answer 18

• Insulin and glucose infusion used to drive K+ into cells as insulin stimulates the Na+/K+ ATPase
• Other hormones (e.g. aldosterone and adrenaline) can also stimulate the Na+/K+ ATPase to increase K+ uptake into cells

Question 19

How does the concentration of Na+ and K+ within the glomerular filtrate and plasma relate?

Answer 19

• The [Na+] and [K+] in the GF and plasma are equal

- This is because Na+ and K+ pass freely into the glomeruli

Question 20

Describe the movement of the Na+ in the proximal convoluted tubule?

Answer 20

• In the proximal convoluted tubule majority of the Na+ are absorbed.
• The fraction of Na+ being absorbed stays the same no matter what however the amount be absorbed changes depend on the GFR
• Na+ enters the epithelial cell from the tubular lumen via a Na+/Glucose symporter
• Na+ also enters the epithelium cell from the tubular limen vai a Na+/H+ antiporter
• Na+ is transported out of the cell into the ECF and K+ is transported into the epithelial cell from the ECF via the Na+/K+ ATPase

Question 21

Describe the movement of K+ in the proximal convoluted tubule

Answer 21

• A small amount of K+ is able to leak into the ECF from epithelial cells via pores
• As more substances are removed from the tubular lumen the K+ gets more concentrated
• This allows for passive diffusion of K+ (and other substances) through gap junctions in between the epithelial cells in the ECF. This diffusion is passive and paracellular

Question 21

Describe the movement of K+ in the proximal convoluted tubule

Answer 21

• A small amount of K+ is able to leak into the ECF from epithelial cells via pores
• As more substances are removed from the tubular lumen the K+ gets more concentrated
• This allows for passive diffusion of K+ (and other substances) through gap junctions in between the epithelial cells in the ECF. This diffusion is passive and paracellular

Question 21

Describe the movement of K+ in the proximal convoluted tubule

Answer 21

• A small amount of K+ is able to leak into the ECF from epithelial cells via pores
• As more substances are removed from the tubular lumen the K+ gets more concentrated
• This allows for passive diffusion of K+ (and other substances like Cl-) through gap junctions in between the epithelial cells in the ECF. This diffusion is passive and paracellular
• From here they are reabsorbed into the proximal convoluted tubule

Question 22

Describe the movement of substances in/out of the loop of Henle.

Answer 22

• In the descending arm of the loop of Henle there is excretion of water from the Loop of Henle into the surrounding interstitial fluid
• In the ascending arm there is a three way transporter which transports Na+, Cl- and K+ into the cell
• There is a Na+/K= ATPase which drives Na+ out of the epithelial cell into interstitial fluid and drives K+ into the cell from the surroundings
• K+ can also be excreted via pores in the cell membrane
• Finally the cell is impermeable to water so cannot directly take it in

Question 23

How do loop diuretics affect [K+]?

Answer 23

• They inhibit the three way transporter which is responsible for bringing in Cl-, K+ and Na+ into the cell

Question 24

How is secretion of K+ into urine controlled?

Answer 24

• At the distal convoluted tubule majority of the K+ that was filtered by the glomerulus has been reabsorbed by the proximal convoluted tubule and loop of Henle
• Excretion of K+ into the urine is controlled by K+ secretion mechanism which is carried out by principle cells in the late distal convoluted tubules and collecting ducts

Question 25

Describe the movement of K+ in the principle cells of the late Distal Convoluted Tubule and collecting ducts?

Answer 25

• Na+ moves out of the cell into the blood and K+ moves into the principle cell from the blood via the Na+/K+ ATPase.
• This creates a high concentration of K+ in the cell which will leak out into the blood via pores in the membrane
• The activation of epithelial Na+ channels (ENaC) by aldosterone causes Na+ to move from the tubular lumen into the principle cell
• This causes a shift in the electrochemical gradient such that K+ will pass from the principle cells into tubular lumen
• K+ also pass out with Cl- into the tubular lumen via a symporter

Question 26

How do potassium sparing diuretics affect K+ transport in principle cells?

Answer 26

• K-sparing diuretics inhibit ENaCs to prevent the movement of Na+ into the principle cell from the tubular lumen
• As a result the shift in electrochemical gradient will not occur and finally the K+ will not dissolve into the tubular lumen

Question 27

What determines K+ secretion in the DCT?

Answer 27

• Increased K+ intake
• Changes in pH as alkalosis causes increased excretion of K+ and decreased serum [K+] whereas in acidosis there is decreased excretion of K+ and increased serum [K+]

Question 28

How does increased [K+] cause increased secretion of K+?

Answer 28

• It slows exit from basolateral membrane as it prevents K+ leaking from the pores into the blood. This causes an increase in the intracellular [K+] causing a concentration gradient between the cell and the lumen of the tubule
• Increases activity of Na+/K+ ATPase which further increases intracellular [K+] which will further increase the movement of K+ into the lumen of the tubule which is facilitated by ENaCs
• It stimulates aldosterone secretion

Question 29

How does aldosterone affect K+ in the body?

Answer 29

• Aldosterone is the major regulator of K+ balance in the body
• Increased K+ intake in the diet leads to increased plasma K+
• This stimulates an increase in the secretion of aldosterone in the adrenal cortex
• This means there is more aldosterone in the plasma leading to increased secretion of K+ in the distal convoluted tubules and collecting ducts
• Finally this leads to an increased excretion of K+ in the urine

Question 30

How does aldosterone work to control K+ secretion?

Answer 30

• Aldosterone increases the activity of the K+/Na+ ATPase which increases K+ influx
• Ultimately this increases intracellular K+ creating a concentration gradient that favours K+ secretion
• It also increases the activity of ENaCs causing increased Na+ reabsorption in the principle cells
• This creates an electrochemical gradient which further assists with the secretion of K+ into the tubular lumen
• It redistributes ENaCs from intracellular organelles to the membrane allwoing for increased influx of Na+
• Finally it also increases the permeability of the luminal membrane to K+ allowing increased secretion of K+

Question 31

How does pH affect K+ movement?

Answer 31

• In a high pH environment the activity of the Na+/K+ ATPase is increased so that we have an increase in intracellular [K+] .
• This favours the K+ secretion into the tubular lumen
• In a low pH environment the activity of the Na+/K+ ATPase is inhibited so that we have a decrease in intracellular [K+] .
• This lowers the K+ secretion into the tubular lumen

Question 32

How does tubular flow rate affect K+ movement?

Answer 32

• An increase in flow rate of fluid in the tubules (caused by increased GFR, inhibition of reabsorption or K-wasting diuretics) dilute the K+ as it is continually washed away
• This favours the electrochemical gradient in which K+ can move from the cells into the tubular lumen (favouring K+ secretion)

Question 33

How does ADH affect K+ movement?

Answer 33

• ADH promotes K+ secretion through the increased activation of K+ channels
• This is similar to aldosterone however it is not as strong/powerful

Question 34

What happens to K+ movement in hypokalaemia?

Answer 34

• In hypokalaemia extra reabsorption of K+ must take place with little to no secretion occurring
• α-Intercalated cells within the late DCT and CD activate to provide additional reabsorption of K+
• It is believed that there is the activation of K+/H+ ATPase which release H+ from the cell into the tubular lumen and takes in K+ from the tubular lumen into the cell
• This promotes K+ reabsorption and so the amount of K+ excreted in the urine is very low

Question 35

How is K+ and Na+ levels balanced at low Extra Cellular Fluid Volume (ECFV)?

Answer 35

• Upon decrease of ECFV the [K+] would rise which stimulates aldosterone secretion in the renal cortex
• This would cause increased K+ secretion and excretion in the CD and late DCT
• Furthermore the decrease in ECFV also causes increased Na+ reabsorption in the PCT which is further supported in the presence of the aldosterone
• The increased absorption of Na+ causes a fall in the flow rate within the tubules
• This fall in flow rate will decrease K+ secretion and excretion
• These two mechanisms work simultaneously to balance each other out resulting in unchanged K+ excretion

Question 36

How does the RAAS system interact with the renal system?

Answer 36

• A fall in blood pressure would be detected by the juxtaglomerular apparatus and a fall in Na+ is detected by the macula densa
• The detection of these stimuli triggers the release of renin
• Renin is converted to angiotensin II which causes the adrenal cortex to secrete aldosterone
• The angiotensin II causes vasoconstriction which increases blood pressure
• High levels of angiotensin II can also inhibit renin secretion
• Aldosterone can also be secreted when there are high levels of plasma [K+]
• This aldosterone promotes Na+ reabsorption and water secretion in principle cells of the late DCT and CD
• By increasing the volume of the blood (through water reabsorption) it increases blood pressure and increases Na+ levels in the blood (and opposes our initial stimuli)
• Aldosterone also promotes K+ and Na+ reabsorption while promoting H+ secretion in α-Intercalated cells

Question 37

Where is the adrenal gland located?

Answer 37

• It sits on top of the kidneys

Question 38

What does the adrenal cortex produce?

Answer 38

• Glucocorticoid hormones (e.g. cortisol)
• Sex hormones (androgens and estrogens)
• Mineralocorticoid hormones (e.g. aldosterone)

Question 39

What is Addison’s disease?

Answer 39

• A primary adrenal insufficiency (lack of activity of the adrenal gland) which is rare compared to secondary adrenal insufficiency
• It is caused by damage to the adrenal cortex which decreases hormone production and numerous symptoms
• It causes a deficiency in aldosterone which leads to the body secreting large amounts of Na+ and low serum Na+ levels (low Na+ levels in the blood)
• This means the body retains more K+ leading to hyperkalaemia
• Treatment involves corticosteroids to replace the ones the adrenal glands are unable to produce

Question 40

What is secondary adrenal insufficiency?

Answer 40

• This is when a condition or a disease ultimately leads to the hinderance in function of the adrenal cortex
• Normal the pituitary glands secrete adrenocorticotropin which is required for adrenal gland function
• Some conditions can impair adrenocorticotropin release which decrease cortisol release
• Ultimately this causes the adrenal glands to shrink which means the patient is unable to produce sufficient amounts of adrenal hormones

Question 41

What is Conn’s syndrome?

Answer 41

• This is primary aldosteronism whihc is caused due to an aldosterone producing adenoma in the adrenal gland
• As a result it leads to hyperaldosteronism without any control mechanism
• An increase in plasma aldosterone will stimulate the kidneys to reabsorb more Na+ and excrete more K+
• This leads to hypertension which increases fluid volume
• Ultimately we end up with hypokalaemia, hypernatremia (excess Na+) and alkalosis
• Furthermore an increase in the blood pressure and Na+ delivery to the macula densa we end up with a decrease in renin
• As a result we experience hypertension which is independent of renin so is very difficult to control using drugs which control the RAAS

Question 42

How is Conn’s syndrome treated?

Answer 42

• The tumour is surgically removed from the adrenal gland

- Hypertension and hypokalaemia controlled with K+-sparing agents