45) Potassium Balance Flashcards
1
Q
Where are the potassium ions found within the body?
A
- 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
2
Q
How are K+ balanced between the two stores?
A
- 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+
3
Q
How can we influence the amount of K+ in the body?
A
- We take in K+ through our diet
- We give out K+ through urine, stools (faeces) and sweat
4
Q
What are the different regulation of K+?
A
- 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)
5
Q
What is the function of K+?
A
- 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
6
Q
How is the difference in intracellular and extracellular K+ concentrations maintained?
A
- 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)
7
Q
How is a slight change in plasma [K+] dealt with when regulating K+ distribution?
A
- 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
8
Q
What are deficiencies in K+ concentration called?
A
- Hyperkalaemia: When plasma [K+] is higher than normal
- Hypokalaemia: When plasma [K+] is lower than normal
9
Q
What is the resting membrane potential?
A
- 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
10
Q
Why are small changes in plasma [K+] dangerous?
A
- 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
11
Q
What changes are seen in an ECG when a patient suffers from hyperkalaemia and hypokalaemia?
A
- 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
12
Q
What is the threshold potential?
A
- The membrane potential which a cell must surpass in order for the cell to fire an action potential
13
Q
How are excitable cells affected by hypokalaemia and hyperkalaemia?
A
- 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
14
Q
How is hypokalaemia caused?
A
- 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
15
Q
What does hypokalaemia cause?
A
- Decreased resting potential
- Decreased release of adrenaline, aldosterone and insulin
16
Q
How is hyperkalaemia caused?
A
- 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
17
Q
What can hyperkalaemia cause?
A
- It can be life threatening as it causes asystolic cardiac arrest
18
Q
How is hyperkalaemia treated?
A
- 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
19
Q
How does the concentration of Na+ and K+ within the glomerular filtrate and plasma relate?
A
- The [Na+] and [K+] in the GF and plasma are equal
- This is because Na+ and K+ pass freely into the glomeruli
20
Q
Describe the movement of the Na+ in the proximal convoluted tubule?
A
- 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
21
Q
Describe the movement of K+ in the proximal convoluted tubule
A
- 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
21
Q
Describe the movement of K+ in the proximal convoluted tubule
A
- 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
21
Q
Describe the movement of K+ in the proximal convoluted tubule
A
- 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
22
Q
Describe the movement of substances in/out of the loop of Henle.
A
- 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
23
Q
How do loop diuretics affect [K+]?
A
- They inhibit the three way transporter which is responsible for bringing in Cl-, K+ and Na+ into the cell
24
Q
How is secretion of K+ into urine controlled?
A
- 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
25
Q
Describe the movement of K+ in the principle cells of the late Distal Convoluted Tubule and collecting ducts?
A
- 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
26
Q
How do potassium sparing diuretics affect K+ transport in principle cells?
A
- 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
27
Q
What determines K+ secretion in the DCT?
A
- 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+]
28
Q
How does increased [K+] cause increased secretion of K+?
A
- 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
29
Q
How does aldosterone affect K+ in the body?
A
- 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
30
Q
How does aldosterone work to control K+ secretion?
A
- 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+
31
Q
How does pH affect K+ movement?
A
- 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
32
Q
How does tubular flow rate affect K+ movement?
A
- 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)
33
Q
How does ADH affect K+ movement?
A
- ADH promotes K+ secretion through the increased activation of K+ channels
- This is similar to aldosterone however it is not as strong/powerful
34
Q
What happens to K+ movement in hypokalaemia?
A
- 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
35
Q
How is K+ and Na+ levels balanced at low Extra Cellular Fluid Volume (ECFV)?
A
- 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
36
Q
How does the RAAS system interact with the renal system?
A
- 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
37
Q
Where is the adrenal gland located?
A
- It sits on top of the kidneys
38
Q
What does the adrenal cortex produce?
A
- Glucocorticoid hormones (e.g. cortisol)
- Sex hormones (androgens and estrogens)
- Mineralocorticoid hormones (e.g. aldosterone)
39
Q
What is Addison’s disease?
A
- 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
40
Q
What is secondary adrenal insufficiency?
A
- 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
41
Q
What is Conn’s syndrome?
A
- 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
42
Q
How is Conn’s syndrome treated?
A
- The tumour is surgically removed from the adrenal gland
- Hypertension and hypokalaemia controlled with K+-sparing agents
