Hypokalemia pathophysiology

; Associate Editor-In-Chief: ; Assistant Editor(s)-In-Chief: Jack Khouri

Overview
Potassium regulation is essential to maintain a normal activity of excitable cells. Failure to regulate potassium serum levels can have severe consequences on several organs especially the heart and the nervous system. Normally, total potassium excretion in stool is low and most ingested potassium is absorbed. The kidney is the main regulator of potassium balance through excretion (the kidney excretes 90-95% of dietary potassium); the gut excretes a minimal amount of dietary potassium (approximately 10%).

The role of the kidney
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. The absorption of sodium by the principal cells of the cortical collecting ducts is mediated by the apical epithelial sodium channels (ENaC); when the amount of sodium delivered to the cortical collecting duct is very high, the absorption of sodium increases without concomitant absorption of the accompanying anions (eg, bicarbonates and chloride ions) which are not easy to absorb. This physiologic process causes the formation of a negative charge within the cortical collecting duct lumen causing potassium and proton secretion. Aldosterone increases sodium absorption at the cortical collecting duct by means of enhancing the activity of Na-K-ATPase pumps, and augmenting the number of the ENaC channels.

Factors increasing kidney potassium excretion

 * Aldosterone
 * High urine flow rate
 * High distal sodium delivery
 * Metabolic alkalosis

Some factors affecting potassium distribution between the cells and the extracellular fluid

 * Na/K ATPase
 * Insulin
 * Catecholamines
 * plasma potassium concentration
 * Extracellular pH
 * Hyperosmolarity

The physiologic role of potassium
Potassium is essential for many body functions, especially excitable cells such as muscle and nerve cells. Diet, mostly meats and fruits, is the major source of potassium for the body. Potassium is the principal intracellular cation, with a concentration of about 145 mEq/L, as compared with a normal value of 3.5 - 5.0 mEq/L in extracellular fluid, including blood. More than 98% of the body's potassium is intracellular; measuring it from a blood sample is relatively insensitive, with small fluctuations in the blood corresponding to very large changes in the total bodily reservoir of potassium.

The cellular effect of Hypokalemia
The electrochemical gradient of potassium between intracellular and extracellular space is essential for nerve function; in particular, potassium is needed to repolarize the cell membrane to a resting state after an action potential has passed. Decreased potassium levels in the extracellular space will cause hyperpolarization of the resting membrane potential ie, it becomes more negative. This hyperpolarization is caused by the effect of the altered potassium gradient on resting membrane potential as defined by the Goldman equation. As a result, the cell becomes less sensitive to excitation and a greater than normal stimulus is required for depolarization of the membrane in order to initiate an action potential. Clinically, this membrane hyperpolarization results in muscle flaccid paralysis, rhabdomyolysis (in severe hypokalemia) and paralytic ileus. At the Renal level, hypokalemia can cause metabolic alkalosis due to potassium/proton exchange across the cells and nephrogenic diabetes insipidus.

Pathophysiology of Hypokalemic Heart Arrhythmias
Potassium is essential to the normal muscular function, in both voluntary (i.e skeletal muscle, e.g. the arms and hands) and involuntary muscle (i.e. smooth muscle in the intestines or cardiac muscle in the heart). Severe abnormalities in potassium levels can seriously disrupt cardiac function, even to the point of causing cardiac arrest and death. As explained above, hypokalemia makes the resting potential of potassium [E(K)] more negative. In certain conditions, this will make cells less excitable. However, in the heart, it causes myocytes to become hyperexcitable. This is due to two independent effects that may lead to aberrant cardiac conduction and subsequent arrhythmia:
 * 1) There are more inactivated sodium (Na) channels available to fire, and
 * 2) The overall potassium permeability of the ventricle is reduced (perhaps by the loss of a direct effect of extracellular potassium on some of the potassium channels), which can delay ventricular repolarization.