Pathophysiology

Pathophysiology

Potassium is essential for many body functions, including muscle and nerve activity. The electrochemical gradient of potassium between the 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. 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, a greater than normal stimulus is required for depolarization of the membrane in order to initiate an action potential.
In certain conditions, this will make cells less excitable. However, in the heart, it causes myocytes to become hyperexcitable. Lower membrane potentials in the atrium may cause arrhythmias because of more complete recovery from sodium-channel inactivation, making the triggering of an action potential more likely. In addition, the reduced extracellular potassium (paradoxically) inhibits the activity of the I_Kr potassium current^[11] and delays ventricular repolarization. This delayed repolarization may promote reentrant arrythmias.

Urinary loss

Urinary loss

• Certain medications can cause excess potassium loss in the urine. Diuretics, including thiazide diuretics (e.g. hydrochlorothiazid) and loop diuretics (e.g. furosemide) are a common cause of hypokalemia. Other medications such as the antifungal, amphotericin B, or the cancer drug, cisplatin, can also cause long-term hypokalaemia.
• A special case of potassium loss occurs with diabetic ketoacidosis. In addition to urinary losses from polyuria and volume contraction, there is also obligate loss of potassium from kidney tubules as a cationic partner to the negatively charged ketone, β-hydroxybutyrate.
• Hypomagnesemia can cause hypokalemia. Magnesium is required for adequate processing of potassium. This may become evident when hypokalaemia persists despite potassium supplementation. Other electrolyte abnormalities may also be present.
• Alkalosis can cause transient hypokalemia by two mechanisms. First, the alkalosis causes a shift of potassium from the plasma and interstitial fluids into cells; perhaps mediated by stimulation of Na⁺-H⁺ exchange and a subsequent activation of Na⁺/K⁺-ATPase activity.^[3] Second, an acute rise of plasma HCO₃^- concentration (caused by vomiting, for example) will exceed the capacity of the renal proximal tubule to reabsorb this anion, and potassium will be excreted as an obligate cation partner to the bicarbonate.^[4] It should be noted that metabolic alkalosis is often present in states of volume depletion, so potassium is also lost via aldosterone-mediated mechanisms.
• Disease states that lead to abnormally high aldosterone levels can cause hypertension and excessive urinary losses of potassium. These include renal artery stenosis and tumors (generally non-malignant) of the adrenal glands. Hypertension and hypokalaemia can also be seen with a deficiency of the 11-beta-hydroxysteroid dehydrogenase type 2 enzyme which allows cortisols to stimulate aldosterone receptors. This deficiency -- known as apparent mineralocorticoid excess syndrome -- can either be congenital or caused by consumption of glycyrrhizin, which is contained in extract of licorice, sometimes found in herbal supplements, candies and chewing tobacco.
• Rare hereditary defects of renal salt transporters, such as Bartter syndrome or Gitelman syndrome, can cause hypokalemia, in a manner similar to that of diuretics. As opposed to disease states of primary excesses of aldosterone, blood pressure is either normal or low in Bartter's or Gitelman's.