Potassium Balance

Question 1

What is the typical daily intake of potassium? Name some foods with high potassium.

Answer 1

About 50-125mmol. Potassium is found in particularly leafy vegetables and most fruit and fruit juice and in potatoes, especially if they are fried (high salt) or baked.

Question 2

Where is most potassium in the body found?

Answer 2

About 95% is within cells (around 150mmol/L), the rest is extracellular (around 4.5mmol/L). Note that different cell types also have different amounts of potassium.

Question 3

What is the main regulator between the intracellular and extracellular compartments?

Answer 3

3Na+/2K+ ATPase pump. This is known as internal balance.

Question 4

Name some hormones which are responsible for regulating internal balance.

Answer 4

insulin, adrenaline, aldosterone and it can be affected by pH.

Question 5

What is external balance?

Answer 5

The homeostasis that occurs between what is taken into the body in the diet and what is excreted out and it is the kidneys that play a major role in this. External balance regulates urinary K+ excretion/retention to affect the overall K+ balance in the body.

Question 6

What are the two types of potassium regulation?

Answer 6

• Acute regulation – Which is distribution of K+ through the ICF and ECF compartments
• Chronic regulation – Achieved by the kidney adjusting K+ excreting and reabsorption

Question 7

List the functions of potassium.

Answer 7

1. Its levels are so high intracellularly, it has an important role in determining intracellular fluid osmolality and hence cell volume.
2. It determines the resting membrane potential (RMP).
3. It affects vascular resistance.

Question 8

Clinically, define the terms Hyperkalemia and Hypokalemia.

Answer 8

• Plasma [K+] > 5.5mM = Hyperkalemia
• Plasma [K+] <3.5mM = Hypokalaemia
Plasma [K+] MUST NOT rise above 6.5mmol/L

Question 9

What is an ionic gradient?

Answer 9

Two gradients combined, the combination of chemical and electrical gradients. Mainly potassium and sodium which determine these gradients.

Question 10

What is the Nernst Equation?

Answer 10

E = (RT/zF) x (ln[X]0)/[X]i
E = Nerst equilibrium potential
R = Ideal gas constant
T = Temperature (in kelvin)
z = Charge of ion
F = Faradays number
X = the element (either Na or K)

Question 11

What does the Nernst equation tell us?

Answer 11

The Nerst equation tells us the equilibrium potential (i.e. when net movement stops) and we can use this to calculate the membrane potential. Because you have conc. gradient pushing K+ out but the electrical positivity on outside pushing it in.

Question 12

What happens to the Ek (Nernst equilibrium potential for K) values when patient is hyperkalaemic and hypokalaemic?

Answer 12

Normal: [K+]o = 3.5mM and [K+]i = 140Mm - EK = -98.5
Hyperkalemia: [K+]o = 7mM and [K+]i = 140mM - EK = -80
Hypokalemia: [K+]o = 1.5mM and [K+]i = 140mM EK = -121.5
In hyperkalemia, the equilibrium potential for K+ is more positive, i.e. so RMP is closer to a position of depolarisation. When you drop the K+ equilibrium potential in hypokalemia you move the RMP closer to hyperpolarisation.

Question 13

What part of the body do the changes in RMP have an effect on and how?

Answer 13

Changes in RMP can severely affect the heart, this is by causing cardiac cell membrane potential depolarisations/hyperpolarisations, this produces characteristic changes in ECG.

Question 14

Causes of Hypokalaemia

Answer 14

Renal or extra-renal loss (stool, sweat) of K+ or by restricted intake. E.g.
• Long standing use of diuretics without KCl compensation
• Hyperaldosteronism/Conn’s syndrome
• Prolonged vomiting -> fluid loss/(Na+ loss? )= Increased aldosterone secretion = K+ excretion in kidneys
• Profuse diarrhoea (diarrhoea fluid contains 50mM K+)

Question 15

What does hypokalaemia result in?

Answer 15

In decreased release of adrenaline, aldosterone and insulin, to prevent shifting into the cell.

Question 16

Causes of Hyperkalaemia

Answer 16

Hyperkalaemia is normal following prolonged exercise, as muscle breaks down (and muscle cell contains very high K+) it gets released into plasma. The kidneys do cope with this easily by excreting it.

Question 17

What disease states can result in Hyperkalaeimia?

Answer 17

disease states can result in problems:
• Insufficient renal excretion
• Increased release from damaged body cells (e.g. during chemotherapy, long-lasting hunger, prolonged exercise or severe burns)
• Long term use of potassium-sparing diuretics
• Addisons disease (adrenal insufficiency)

Question 18

What happens if the concentration of plasma K+ is above 7mM and how can this be solved?

Answer 18

This is life-threatening, can result in asystolic cardiac arrest. So, in this situation you can give insulin/glucose infusion to drive K+ back into cells.
Insulin is extremely important, the mechanism however is unclear, it may stimulate the Na+/K+ pump. Glucose is given with it to prevent hypoglycemia.

Question 19

Why is maintenance of normal K+ homeostasis an increasingly important limiting factor in therapy of CVD?

Answer 19

• Various drugs like beta-blockers, ACE inhibitors etc. raise serum [K+], increasing risk of hyperkalemia.
• Conversely loop diuretics, used to treat heart failure, enhance the risk of hypokalemia.

Question 20

Where is the majority of K+ and Na+ reabsorbed in the kidneys?

Answer 20

Between 60-70% of Na+ and K+ is reabsorbed in the PCT. The fraction that is reabsorbed in the PCT is always kept constant, but the absolute amount reabsorbed will vary with GFR (always same %). 90% of filtered K+ is reabsorbed in PCT and LoH
*Human kidneys are designed to conserve Na+

Question 21

What substances are absorbed at the end of the early PCT?

Answer 21

So [Na+] is high in the tubular lumen compared to cells, so it moves down its concentration gradient and in doing so carries various other substances with it. Essentially all glucose, AA and most bicarb has been reabsorbed.

Question 22

What are the different ways the ions can be reabsorbed in the PCT?

Answer 22

K+ can passively diffuse down its concentration gradient through leak channels back into blood.
Can also be Cl-, K+ and to a degree Na+ just passively diffusing into blood down their gradients via the paracellular route through the tight junctions, they do this as water moves across.

Question 23

Why does water flow from the tubular lumen into the ECF? How can this be stopped?

Answer 23

The Na+/K+ pump transports Na+ out of the cell and into the ECF. This creates an osmotic gradient.
If the channel is blocked e.g. by dopamine or digitalis.

Question 24

Describe the permeability of the LoH to water.

Answer 24

Descending limb is very permeable to water but the ascending limb (both thin and thick) are impermeable (water cannot move out).

Question 25

Describe what happens to the filtrate as it moves through the LoH.

Answer 25

Filtrate enters the descending limb and water leaves (down its osmotic gradient), the filtrate gets more and more concentrated reaching a peak of 1200mOsm/L at the tip of LoH.
In ascending limb, the characteristics change (it is impermeable to H2O but permeable to solutes). NaCl leaves the tubule and enters into the ECF. Because water can’t leave, the fluid becomes more dilute and osmolality decreases, it becomes hyposomotic (100mOsm/L)

Question 26

What happens to the filtrate in the ascending limb of the LoH?

Answer 26

Na/2Cl-/K+ symporter, present on the luminal membrane (taking from lumen into cell). This is driven by the [Na+] gradient, from lumen to cell (caused by Na+/K+ ATPase on basolateral). On luminal side you also have the Na+/H+ antiporter.
On basolateral side, as said you have the Na+/K+ pump. As there will be a lot of K+ in the cell there is a lot of movement out of the cell into blood, contributing to interstitial fluid making it hyperosomtic, it will also diffuse in vasa recta and small amount into descending limb.
**Na/2Cl-/K+ symporter is inhibited by loop diuretics.