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
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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+
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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

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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)
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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
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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)
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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
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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

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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
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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
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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
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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
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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
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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
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15
Q

What does hypokalaemia cause?

A
  • Decreased resting potential

- Decreased release of adrenaline, aldosterone and insulin

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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
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17
Q

What can hyperkalaemia cause?

A
  • It can be life threatening as it causes asystolic cardiac arrest
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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
How do loop diuretics affect [K+]?
- They inhibit the three way transporter which is responsible for bringing in Cl-, K+ and Na+ into the cell
24
How is secretion of K+ into urine controlled?
- 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
Describe the movement of K+ in the principle cells of the late Distal Convoluted Tubule and collecting ducts?
- 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
How do potassium sparing diuretics affect K+ transport in principle cells?
- 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
What determines K+ secretion in the DCT?
- 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
How does increased [K+] cause increased secretion of K+?
- 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
How does aldosterone affect K+ in the body?
- 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
How does aldosterone work to control K+ secretion?
- 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
How does pH affect K+ movement?
- 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
How does tubular flow rate affect K+ movement?
- 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
How does ADH affect K+ movement?
- ADH promotes K+ secretion through the increased activation of K+ channels - This is similar to aldosterone however it is not as strong/powerful
34
What happens to K+ movement in hypokalaemia?
- 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
How is K+ and Na+ levels balanced at low Extra Cellular Fluid Volume (ECFV)?
- 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
How does the RAAS system interact with the renal system?
- 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
Where is the adrenal gland located?
- It sits on top of the kidneys
38
What does the adrenal cortex produce?
- Glucocorticoid hormones (e.g. cortisol) - Sex hormones (androgens and estrogens) - Mineralocorticoid hormones (e.g. aldosterone)
39
What is Addison's disease?
- 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
What is secondary adrenal insufficiency?
- 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
What is Conn's syndrome?
- 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
How is Conn's syndrome treated?
- The tumour is surgically removed from the adrenal gland | - Hypertension and hypokalaemia controlled with K+-sparing agents