Hyperkalemia pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]
Overview
Potassium is the most abundant intracellular cation and is critically important for many physiologic processes.The normal range of potassium in blood is 3.5-5.1meq/L .Hyperkalemia develops when the level of potassium exceeds 5.5 meq/L in blood which can be due to an increase in intake of potassium, excessive production as seen in tissue breakdown, ineffective elimination of potassium or some drugs. The potassium levels in the body are highly regulated mainly by renal excretion.The gut excretes a minimal amount of dietary potassium (approximately 10%). Hyperkalemia is very common in patients with chronic kidney disease as potassium is not effectively excreted from the body.Potassium is involved in maintaining transmembrane potentials of cells,so imbalance in potassium levels can lead to disruption of cell membrane potentials and can cause hyperexcitablity leading to fatal cardiac arrhythmias and effecting nervous system.
Pathophysiology
Physiological role of potassium
Potassium is the major intracellular cation and sodium is the major extracellular cation.Almost all cells possess an Na+-K+-ATPase, which pumps Na+ out of the cell and K+ into the cell and leads to a K+ gradient across the cell membrane (K+in>K+out) that is partially responsible for maintaining the potential difference across the membrane.This potential difference called the transmembrane potential is responsible for the excitability of the cells.
Factors affecting transcellular shift of potassium
The distribution of potaasium inside and outside the cells is maintained by various pumps,osmolarity,ph and the hormones insulin, aldosterone, beta 2-catecholamines, alpha-catecholamines, and prostaglandins.
- Insulin regulates potassium uptake into the cells through GLUT receptors on the cell membranes by increasing the activity of Na+-K+-ATPase pump.
- Catecholamines regulate potassium uptake into the cells through β2-Receptor–induced stimulation of Na+-K+-ATPase pump.
- Increased osmolarity as in hyperglycemia causes water efflux from the cells that drags potassium along.
- In acidosis,the decreased extracellular ph decreases the rate of Na+-H+ exchange (NHE1) and inhibit the inward rate of Na+-3HCO3 cotransport,thus decreasing intracellular Na+ levels which in turn decreases the activity of Na+-K+-ATPase pump and decreasing intracellular K+ levels.
- In alkalosis,the increased extracellular ph increases the rate of Na+-H+ exchange (NHE1) and increases the inward rate of Na+-3HCO3 cotransport,thus increasing intracellular Na+ levels which in turn increases the activity of Na+-K+-ATPase pump and increasing intracellular K+ levels.
Role of kidneys
The source of potassium to the body is diet.The potassium levels in the body are dependent on dietary intake,tissue breakdown,gastrointestinal absorption and losses and most important is renal regulation via absorption and secretion.Kidney play a important role in keeping the balance of potassium. At the glomerulus, potassium is freely filtered and then largely reabsorbed in the proximal tubule and thick ascending loop of Henle (>60 % of filtered potassium). The cortical collecting duct receives 10–15% of filtered potassium and constitutes the kidney’s major site of potassium excretion. Potassium excretion at the cortical collecting duct depends on the amount of sodium delivered there and the activity of aldosterone.It does so by the following ways.
- increases intracellular K+ concentration by stimulating the activity of the Na+-K+-ATPase in the basolateral membrane.
- stimulates Na+ reabsorption across the luminal membrane, which increases the electronegativity of the lumen, thereby increasing the electrical gradient favoring K+ secretion.If the rate of delivery of sodium and water is very high in the distal tubules then it will cause more Na+ reabsorption and more K+ secretion.
- has a direct effect on the luminal membrane to increase K+ permeability.
Aleration in the levels of potassium occur due to disruption in the above mentioned mechanisms that regulate potassium homeostasis. Hyperkalemia is the increased levels of potassium (>5.1 meq/L) in blood.It can be caused by increase in transcellular shift of potassium,impaired excretion from the kidneys or excessive intake.