Potassium homeostasis Flashcards
K+ in a 70kg person
3500mEq/L
How much K+ is in muscle cells?
80% in muscle cells and
How much K+ is in ECF?
Around 70mEq/L (2%) in their ECF
Intracellular K+
140mM
Extracellular K+
4mM
What helps maintain the 30 fold ICF/ECF K+ gradient?
Em of K+, high permeability to K+
Na/KATPase (2K+ in, 3Na+ out)
What organ is responsible for LT regulation of K+?
Kidney
Hypokalemia
Low extracellular K+ (<3.6mM). Caused by excessive diuretic use, severe burns and diarrheal infections such as cholera.
Hyperkalemia
High extracellular K+ (>4.4mM). Causes by crush injuries and renal failure.
Factors that affect extracellular [K+] homeostasis via effect on the Na+/K+ATPase
Insulin: Decreases (upreg pump)
Acid/base balance: acid increases, alkali decreases
Catecholamines: increase and decrease
Hypoxia: increase
Exercise: increase
Hyperosmolarity: increase
Insulin role on K+
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)
Catecholamine role on K+
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+)
Aldosterone action on K+
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.
In exercise what effect does aldosterone have? Why can it lead to hypokalemia (arrhythmias) post exercise?
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.
Hypoxia on K+
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
Acidosis on K+
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.
What is the only acid to effect EC K+?
Mineral acid NOT organic acid (lactate)
Why does mineral acid cause hyperkalemia?
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.
Exercise induced hyperkalemia
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.
Hyperkalemia causing skeletal muscle fatigue
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.
Hyperkalemia regulates exercise blood flow
Exercise increases muscle blood flow, K+ is a potent vasodilator (metabolic hyperaemia)
Hyperkalemia regulates arterial bp
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.
Hyperkalemia increases arterial chemoreceptor sensitivity
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
Myocardial stability
The combination of noradrenaline (sympathetic) and K+ released in exercise are able to offset eachothers potentially catastrophic effects on the body (and heart).
Cardiac effect of high sympathetic drive
Pro-arrhythmogenic
less filling time, likely to cause after depolarisations
Cardiac effect of hyperkalemia
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
How does the combination of hyperkalemia and high sympathetic drive produce myocardial stability?
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.
Hyperkalemia ECG
T wave elevation can exceed the R wave, Q-T interval is shorter
Hypokalemia ECG
T wave flatter, Q-T interval is longer, appearance of a U wave and long AP duration.
How can hypokalemia be pro-arrhythmogenic
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.
Name three circumstances in which plasma potassium rises.
Exercise
Renal failure
Metabolic acidosis
Name two consequences of a doubling of plasma potassium.
Skeletal muscle fatigue
Decrease inotropy
Name two conditions which can raise plasma potassium.
Diabetes type 1 (decreased insulin) Addisons disease (decreased aldosterone)
Name two hormones which act on non-renal mechanisms to lower plasma potassium.
Insulin
Adrenaline
The two most important hormones for the regulation of extracellular K+ concentration within normal limits are
Insulin and aldosterone
Normal K+ intake and output per day
100mmol
Hyperkalaemia in severe case treated with low doses of
Catecholamines
