Potassium balance

Question 1

What is our daily intake of potassium?

Answer 1

A typical daily intake in the UK is 50-125mmol.

Question 2

Where do we obtain potassium from?

Answer 2

• Potassium is found particularly in leafy vegetables and most fruit and fruit juice, and in potatoes, especially if they are fried* or baked.
• high salt content

Question 3

Describe potassium homeostasis

Answer 3

On image

Question 4

What does regulation of potassium homeostasis imply?

Answer 4

Acute regulation:
- Distribution of K+ through ICF and ECF compartments
Chronic regulation:
- Achieved by the kidney adjusting K+ excretion & reabsorption

Question 5

How does a sodium-potassium pump work?

Answer 5

On image

Question 6

When does ECF pool change?

Answer 6

ECF pool will change more dramatically with changes in body K distribution e.g. after a meal, get slight increase in plasma [K+], which is shifted into ICF compartment

Question 7

When does internal balance and acute regulation shift?

Answer 7

Shift mainly subject to hormonal control:
Insulin
Adrenaline
Aldosterone
pH changes

Question 8

Define Hyperkalaemia and Hypokalaemia

Answer 8

Hyperkalaemia = plasma [K+] > 5.5mM

Hypokalaemia = plasma [K+] < 3.5mM

Question 9

What creates a resting membrane potential?

Answer 9

Ionic gradients (i.e. combination of chemical & electrical gradients)

Question 10

What does the Nerst equation determine?

Answer 10

Resting membrane potential of the ions (potassium and sodium)

These ions determine resting membrane potential

Question 11

What happens when plasma [K+] is altered above or below normal (its effect on the membrane potential)

Answer 11

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

Question 12

What can changes in potassium cause?

Answer 12

Can severely affect the heart - cardiac cell membrane potential (depolarisations/hyperporlarisations) producing characteristic changes in ECG

Question 13

What is cell membrane hyperpolarisation and depolarisation?

Answer 13

Cell membrane hyperpolarization – increased negativity of voltage across membrane, hence decreased excitability of neurones & muscle cells

Cell membrane depolarization – decreased negativity of voltage, hence threshold approached quicker, increased excitability & muscle contractions

Question 14

What effect does Hyperkalaemia and Hypokalaemia have on the ECG?

Answer 14

Hyperkalaemia: ↑QRS complex, ↑amplitude T-wave, eventual loss P-wave

Hypokalaemia: ↓amplitude T-wave, prolong Q-U interval, prolong P-wave

Question 15

When can Hypokalaemia caused by renal or extra-renal loss of K+ or by restricted intake occur and cause?

Answer 15

Long-standing use of diuretics w/out KCl compensation
Hyperaldosteronism/Conn’s Syndrome
(increases aldosterone secretion)
Prolonged vomiting → Na+ loss → aldosterone secretion → K+ excretion in kidneys
Profuse diarrhoea (diarrhoea fluid contains 50mM K+)

Question 16

What does Hypokalaemia result in?

Answer 16

Hypokalaemia results in ↓release of adrenaline, aldosterone & insulin

Question 17

When does acute hyperkalaemia normally occur?

Answer 17

Acute hyperkalaemia normal following prolonged exercise → normal kidneys excrete K+ easily

Question 18

What disease states can occur as a result of Hyperkalaemia?

Answer 18

Insufficient renal excretion
Increased release from damaged body cells eg. during chemotherapy, long-lasting hunger, prolonged exercise or severe burns
Long-term use of Potassium-sparing diuretics
Addison’s disease (adrenal insufficiency)

Question 19

When plasma concentration of potassium is greater than 7mM what can it cause?

Answer 19

asystolic - > cardiac arrest

Question 20

How does insulin and glucose drive potassium back into cells?

Answer 20

Insulin extremely important – mechanism unclear, may stimulate Na-K-ATPase. Why is glucose given with it?

Question 21

What other hormones stimulate the Na+-K+ pump?

Answer 21

Other hormones (aldosterone, adrenaline) stimulate Na+-K+ pump -> cellular K+ influx

Question 22

What is external balance of potassium maintained by?

Answer 22

The kidney

Question 23

How is potassium involved in the treatment of CVD?

Answer 23

Drugs like β-blockers, ACE inhibitors etc raise serum [K] →risk of hyperkalaemia

Conversely loop diuretics, used to treat heart failure, enhance risk of hypokalaemia

K+ excretion in the stools is not under regulatory control ⇒large amounts can be lost by extra-renal routes

Question 24

What is the concentration of soidum and potassium in the BC

Answer 24

On image

Question 25

What percentage of Na/+K+ is reabsorbed in the PCT?

Answer 25

60-70% Fraction that is reabsorbed in PCT is ~ constant Although absolute amount reabsorbed varies with GFR

Question 26

Describe potassium movement on PCT What happens if this Na+/ K+ pump is inhibited by dopamine?

Answer 26

1. Potassium diffuses from the sodium-potassium pump from the epithelial cell into the capillaries 2. Also passive across by passive and paracellular mechanisms (K+, Cl-, Na+) If this is inhibited (by for eg dopamine, digitalis) then the Na gradient is dissipated, eventually loose primary Na transport and the associated secondary active solute transport and also NO osmotic gradient for water transport.

Question 27

What determines K+ secretion in DCT? How is this achieved?

Answer 27

1. Increased K+ intake 2. Changes in blood pH - Alkalosis ⇒ ↑excretion of K+ ⇒ ↓serum [K+] - *Acute Acidosis ⇒ ↓excretion of K+ ⇒ ↑serum [K+] 1. activity of Na-K-ATPase pump 2. electrochemical gradient 3. permeability of luminal membrane channel

Question 28

What does aldosterone do?

Answer 28

Aldosterone is major regulator of K balance in the body. It acts to: ↑activity of Na+/K+ pump -> ↑K+ influx -> ↑[K+]i -> cell-lumen concentration gradient ↑ENaC channels -> ↑Na+ reabsorption -> ↓cell negativity and ↑lumen negativity -> voltage gradient Redistributes ENaC from intracellular localization to membrane ↑permeability of luminal membrane to K+ On image

Question 29

How does an ↑Plasma [K] increases K secretion?

Answer 29

slows exit from basolateral membrane -> ↑[K+]i -> cell-lumen concentration gradient ↑activity of Na+/K+ ATPase -> ↑[K+] within cell ↑Plasma [K] -> stimulates aldosterone secretion On image

Question 30

Describe the pathway that leads to an increase in potassium excretion

Answer 30

On image

Question 31

How does alkalosis and acidosis effect secretion of potassium ions?

Answer 31

On image

Question 32

What other factors can cause an increase in potassium excretion?

Answer 32

↑Flow rate by: ↑GFR Inhibition of re-absorption K-wasting diuretics

Question 33

How are alpha-intercalated cells of late DCT/ CD involved in severe hypokalemia?

Answer 33

1. Activation of potassium-hydrogen ATPase increases reabsorption into peritubular capillary

Question 34

Dependence of potassium secretion on sodium and flow poses problems WHY?

Answer 34

Changing effects of sodium or potassium may have unwanted effects on one of these but wanted effects on the other

Question 35

How does a decrease in ECFV cause secretion/ excretion of potassium ions?

Answer 35

On image

Question 36

Describe the RAAS cascade

Answer 36

On image

Question 37

What factors shift K+ into cells and what factors shift potassium out of cells?

Answer 37

On table

Question 38

Describe addisons disease What does the cortex produce? What can damage to the cortex cause? What does a deficiency in aldosterone cause? What treatment option is available for people with Addison's disease?

Answer 38

``` Cortex produces: glucocorticoid hormones (e.g. Cortisol) Mineralocorticoid hormones (e.g. Aldosterone) Sex hormones (androgens & estrogens) ``` Primary Adrenal Insufficiency aka Addison’s disease (very rare ) as opposed to secondary adrenal insufficiency Damage to cortex -> ↓↓ hormone production -> numerous symptoms Deficiency in aldosterone -> body secreting large amounts Na -> low serum Na levels body retaining K-> hyperkalaemia Treatment usually involves corticosteroid (steroid) replacement therapy for life.

Question 39

What does secondary adrenal insufficiency cause?

Answer 39

Pituitary ACTH -> Cortisol Decrease-> Adrenal glands shrink

Question 40

What causes Primary Aldosteronism aka Conn’s Syndrome? What does it cause?

Answer 40

Primary Aldosteronism aka Conn’s Syndrome due to aldosterone-producing adenoma of ZG of adrenal gland usually <3cm, unilateral & renin-unresponsive Hyperaldosteronism (excess release of aldosterone) due to variety chronic disease ``` Most common (50-60%) due to Conn’s syndrome, remaining 40-50% due to bilateral adrenal hyperplasia Aldosterone release in absence of stimulation by Angiotensin II ``` ↑↑↑ Plasma Aldosterone -> kidneys to stimulate Na+ reabsorption & K+ excretion -> develop hypertension* -> ↑fluid volume -> hypokalaemia (↓[K+]), hypernatremia and alkalosis *↑bp & Na delivery to macula densa -> ↓↓release of renin -> renin-independent cause of hypertension (very difficult to control) Treatment: surgical removal of tumour-containing adrenal gland hypertension & hypokalaemia controlled with K+-sparing agents e.g spironolactone