Potassium regulation Flashcards
Extracellular K+ conc
3.5-5.0mM
Intracellular K+ conc
140mM
Describe short-term and long-term control of K+
Short term - movement of K+ into and out of cells
Long term - kidney
What do many of. the short-term mechanisms involve?
Na+/K+-ATPase
What factors affect short-term control?
- insulin
- catecholamines
- aldosterone
- acid base balance
- plasma tonicity
- cell lysis
- strenuous exercise
Describe how insulin affects K+
- short term rises may occur after a meal
- Insulin → binds to its receptor leads to phosphorylation of the insulin receptor substrate protein (IRS-1) → this binds to PI3K → this interaction leads to the activation of a kinase, known as PDK1 → aPKC activation then leads to Na+/K+-ATPase insertion
Loss of the insulin signalling pathway in diabetes mellitus results in hyperkalemia
This can be corrected via insulin injections
Describe how catecholamines may affect K+
β2 also acts via Na+/K+-ATPase → cAMP and PKA-dependent pathway
In contrast, α receptors impair cellular entry
Describe aldosterone in short term control
Serves functions modulating NA+/K+-ATPase but its actions are mainly involved in mediating renal excretion
Describe how acid base balance may have an effect?
- acidosis = hyperkalemia through mechanisms that are not well-understood
- Causes K+ loss from cells
- acidosis → increased rate of Na+/H+ exchange (NHE1_ and inward Na+-3HCO3- cotransport
Consequently, the intracellular Na+ concentration drops, and so Na+-K+-ATPase activity drops, causing a net reduction in cellular K+.
Furthermore, the decrease in extracellular HCO3- concentration favours Cl–HCO3- exchange, increasing the intracellular Cl- concentration. This provokes an increase in K+ efflux by K+-Cl- cotransport.
Describe effects of plasma tonicity
If hyperglycemia occurs, water moves out of the cell, down its water potential gradient, and this movement also causes K+ to exit the cell via solvent drag.
Alternatively, in cell shrinkage, the intracellular K+ concentration rises, favouring K+ efflux.
Describe the role the colon plays in long-term control
GI tract plays minor role in K+ excretion –colon can adjust its K+ excretion in response to certain stimuli (e.g. adrenal hormones, changes in dietary K+, and decreased capacity of the kidneys to excrete K+), but the colon isn’t capable of increasing K+ secretion sufficiently to maintain external K+ balance.
Describe effects of catecholamine agonists and antagonists on K+ levels
Agonists, including adrenaline, salbutamol and insulin, increase uptake of K+ by cells
Beta-antagonists (beta blockers, such as atenolol) prevent this and cause hyperkalaemia in overdose
Describe K+ reabsorption in the PCT
Mainly passive and occurs paracellularly in relation to Na+ and water reabsorption
Describe K+ reabsorption in the LOH
Additional transcellular pathway → NKCC2
Where does K+ secretion begin?
Early DCT and increases along the distal nephron, most occurs in the principal cells of the PD
Describe the process of K+ secretion
Firstly, the K+ is taken up from the interstitium by a sodium-potassium ATPase basolaterally into the epithelial cell
This maintains a favourable gradient for K+ efflux and therefore K+ diffuses out of the cell luminally (and basolaterally)
What is apical K+ permeability in the distal nephron maintained by?
Presence of renal outer medullary potassium channels (ROMK) and big potassium (BK) channels, as well as K+-Cl- cotransporter
What channel can also contribute to K+ rebasorption in the CD in conditions of K+ depletion
apical H+-K+-ATPase on alpha intercalated cells
What are the two key determinants of K+ secretion?
- mineralocorticoid activity
- distal delivery of Na+ and water
What is the body’s major mineralocorticoid?
Aldosterone
Where is aldosterone release from?
Zone glomerulsa of adrenal cortex
What state of K+ triggers aldosterone synthesis? What does aldosterone do to K+ levels?
Released in response to increased plasma K+
Stimulates K+ secretion
How does aldosterone stimulate K+ secretion?
- stimulate Na+/K+-ATPase synthesis and activity → increased intracellular K+
- Upregulating ENaC synthesis → increases NaC reabsorption and increases electronegativity of the lumen, increasing electrical gradient, which favours K+ secretion
- Directly increases K+ permeability of the luminal membrane, thought to be mediated by ROMK
Describe effect of Conn’s on K+?
PRIMARY HYPERALDOSTERONISM → hypokalemia
