Potassium homeostasis

Question 1

K+ in a 70kg person

Answer 1

3500mEq/L

Question 2

How much K+ is in muscle cells?

Answer 2

80% in muscle cells and

Question 3

How much K+ is in ECF?

Answer 3

Around 70mEq/L (2%) in their ECF

Question 4

Intracellular K+

Answer 4

140mM

Question 5

Extracellular K+

Answer 5

4mM

Question 6

What helps maintain the 30 fold ICF/ECF K+ gradient?

Answer 6

Em of K+, high permeability to K+

Na/KATPase (2K+ in, 3Na+ out)

Question 7

What organ is responsible for LT regulation of K+?

Answer 7

Kidney

Question 8

Hypokalemia

Answer 8

Low extracellular K+ (<3.6mM). Caused by excessive diuretic use, severe burns and diarrheal infections such as cholera.

Question 9

Hyperkalemia

Answer 9

High extracellular K+ (>4.4mM). Causes by crush injuries and renal failure.

Question 10

Factors that affect extracellular [K+] homeostasis via effect on the Na+/K+ATPase

Answer 10

Insulin: Decreases (upreg pump)

Acid/base balance: acid increases, alkali decreases

Catecholamines: increase and decrease

Hypoxia: increase

Exercise: increase

Hyperosmolarity: increase

Question 11

Insulin role on K+

Answer 11

When there is increased extracellular K+, more insulin is released by pancreas beta cells (by more than 1mmol/L).

Insulin acts on muscle cell insulin receptors and upregulates the Na+/K+ pump (likely a protein kinase mechanism).

Shifts K+ into cells temporarily so a good clinical treatment for hyperkalemia.

Given as a clinical treatment with dextrose (to prevent hypoglycaemia)

Question 12

Catecholamine role on K+

Answer 12

Can cause both hyper and hypokalemia

Beta 2 agonists: Such as catecholamines and salbutamol act to stimulate the Na+/K+ pump.

Can lead to hypokalemia if taken too heavily in a non-hyperkalemic state. Selective alpha agonists: Cause hyperkalemia

Non-selective adrenergic agonists (adrenaline): detected with an ion sensitive electrode -can cause both states, there is an initial rise in [K+] then a fall to below normal levels.

(Alpha acts first - initial rise in K+, then Beta 2 acts, causes fall in K+)

Question 13

Aldosterone action on K+

Answer 13

Involved in the long term regulation of the Na/K+ pump.

Acts on the nuclear mineralocorticoid receptors (MR) within the principal cells of the distal tubule and the collecting duct of the kidney nephron, it upregulates and activates the basolateral Na+/K+ pump.

This results in more reabsorption of sodium (Na+) and secretion of potassium (K+) ions into the urine (lumen of collecting duct), explains why aldosterone release is also stimulated by increased [K+] in plasma.

Question 14

In exercise what effect does aldosterone have? Why can it lead to hypokalemia (arrhythmias) post exercise?

Answer 14

During exercise, aldosterone production is increased, thereby decreasing urine production and conserving fluid volume, while promoting excretion of potassium.

Helps reduce the accumulation of potassium in blood due to efflux from active skeletal muscle, but contributes to the fall in potassium levels after exercise ceases.

Maintenance of blood volume by moderate fluid intake is likely to minimise excessive engagement of the renin-angiotensin-aldosterone system.

Question 15

Hypoxia on K+

Answer 15

Low levels of O2 lead to decreased ATP availability, thus, less opening of Na+/K+ATP pump - and less movement of K+ into the cells.

Hypoxia leads to hyperkalemia

Question 16

Acidosis on K+

Answer 16

Mineral acid causes a 0.1 unit decrease in pH but an increase of 0.7 mmol/L of [K+]

Low pH inhibits Na/KATPase.

Question 17

What is the only acid to effect EC K+?

Answer 17

Mineral acid NOT organic acid (lactate)

Question 18

Why does mineral acid cause hyperkalemia?

Answer 18

Mineral acid - entry of H+ is incompletely accompanied by Cl-, for cell electroneutrality K+ provides a counter flow exiting the cell.

Renal failure patients often experience rise in potassium this way.

Question 19

Exercise induced hyperkalemia

Answer 19

Exercise causes the efflux of K+ from muscle cells (through delayed rectifier K+ channels).

Hyperkalemia arrises as a result of incomplete K+ reuptake by the Na pump during repolarization of the action potential.

Question 20

Hyperkalemia causing skeletal muscle fatigue

Answer 20

Loss of force generating activity of the muscle

Likely caused by increased K+, causing burning sensation and affected AP propagation.

K+ activates C fibres - causing pain soon after exercise, lactate however peaks 2-3 mins after excersise, thus unlikely to cause pain.

Question 21

Hyperkalemia regulates exercise blood flow

Answer 21

Exercise increases muscle blood flow, K+ is a potent vasodilator (metabolic hyperaemia)

Question 22

Hyperkalemia regulates arterial bp

Answer 22

Muscle pressor reflex - activation of C fibres by K+ in muscles, afferent signal causes sympathetic efferent response, causes vasoconstriction in non-exercising vascular beds (increase BP) also increases HR/CO via sympathetic on the heart.

Question 23

Hyperkalemia increases arterial chemoreceptor sensitivity

Answer 23

K+ can target carotid body chemoreceptors (sensitive to changes in K+).

Afferent via glossopharyngeal, efferent down phrenic nerve.

Hyperkalemia can cause increase in breathing via excitation of arterial chemoreceptors

Question 24

Myocardial stability

Answer 24

The combination of noradrenaline (sympathetic) and K+ released in exercise are able to offset eachothers potentially catastrophic effects on the body (and heart).

Question 25

Cardiac effect of high sympathetic drive

Answer 25

Pro-arrhythmogenic

less filling time, likely to cause after depolarisations

Question 26

Cardiac effect of hyperkalemia

Answer 26

Negatively inotropic

Inward rectifier K+ channels are overactive (higher gradient) which leads to rapid repolarizations.

Smaller calcium transient - negatively inotropic.

Lack of calcium for CICR - acidemia also likely - H+ binds to TrpC before calcium can - negative inotropic.

This can lead to the heart going into cardiac arrest

Question 27

How does the combination of hyperkalemia and high sympathetic drive produce myocardial stability?

Answer 27

Noradrenaline increases inward calcium current negates the negative ionotropic effect that the K+ can have on the heart

Conversely, high potassium shortens the AP by activating IK1 for fast repolarisation, prevents the sympathetic arrhythmic effects of a longer repolarisation.

Question 28

Hyperkalemia ECG

Answer 28

T wave elevation can exceed the R wave, Q-T interval is shorter

Question 29

Hypokalemia ECG

Answer 29

T wave flatter, Q-T interval is longer, appearance of a U wave and long AP duration.

Question 30

How can hypokalemia be pro-arrhythmogenic

Answer 30

Inactivation of inward rectifier K+ channels prevents repolarization.

More calcium into the cell due to longer plateau phase - pro-arrhythmogenic as a more active NCX means net introduction of Na+ into the cell, positive membrane potential - patient at risk of after -depolarization/arrhythmia.

Question 31

Name three circumstances in which plasma potassium rises.

Answer 31

Exercise
Renal failure
Metabolic acidosis

Question 32

Name two consequences of a doubling of plasma potassium.

Answer 32

Skeletal muscle fatigue

Decrease inotropy

Question 33

Name two conditions which can raise plasma potassium.

Answer 33

Diabetes type 1 (decreased insulin)
Addisons disease (decreased aldosterone)

Question 34

Name two hormones which act on non-renal mechanisms to lower plasma potassium.

Answer 34

Insulin

Adrenaline

Question 35

The two most important hormones for the regulation of extracellular K+ concentration within normal limits are

Answer 35

Insulin and aldosterone

Question 36

Normal K+ intake and output per day

Answer 36

100mmol

Question 37

Hyperkalaemia in severe case treated with low doses of

Answer 37

Catecholamines