An ECG in a person with a potassium level of 1.1 meq/L showing the classical changes ofST segment depression, invertedT waves, largeU waves, and a slightly prolongedPR interval.
Causes of hypokalemia include vomiting,diarrhea, medications likefurosemide andsteroids,dialysis,diabetes insipidus,hyperaldosteronism,hypomagnesemia, and not enough intake in the diet.[1] Normal potassium levels in humans are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels below 3.5 mmol/L defined as hypokalemia.[1][2] It is classified as severe when levels are less than 2.5 mmol/L.[1] Low levels may also be suspected based on anelectrocardiogram (ECG).[1] The opposite state is calledhyperkalemia that means high level of potassium in the blood serum.[1]
The speed at which potassium should be replaced depends on whether or not there are symptoms or abnormalities on anelectrocardiogram.[1] Potassium levels that are only slightly below the normal range can be managed with changes in the diet.[3] Lower levels of potassium require replacement with supplements either taken by mouth or givenintravenously.[3] If given intravenously, potassium is generally replaced at rates of less than 20 mmol/hour.[1] Solutions containing high concentrations of potassium (>40 mmol/L) should generally be given using acentral venous catheter.[3]Magnesium replacement may also be required.[1]
Mild hypokalemia is often without symptoms, although it may causeelevation ofblood pressure,[6] and can provoke the development of anabnormal heart rhythm. Severe hypokalemia, with serum potassium concentrations of 2.5–3 meq/L (Nl: 3.5–5.0 meq/L), may causemuscle weakness,myalgia, tremor, andmuscle cramps (owing to disturbed function ofskeletal muscle), andconstipation (from disturbed function ofsmooth muscle). With more severe hypokalemia,flaccid paralysis andhyporeflexia may result. Reports exist ofrhabdomyolysis occurring with profound hypokalemia with serum potassium levels less than 2 meq/L.[7]Respiratory depression from severe impairment of skeletal muscle function is found in some people.[8] Psychological symptoms associated with severe hypokalemia can include delirium, hallucinations, depression, or psychosis.[9][10]
Noteating a diet with enough potassium-containing foods or fasting can cause the gradual onset of hypokalemia. This is a rare cause and may occur in those withanorexia nervosa or those on aketogenic diet.[citation needed]
A more common cause is excessive loss of potassium, often associated with heavy fluid losses that flush potassium out of the body. Typically, this is a consequence ofdiarrhea, excessiveperspiration, losses associated withcrush injury, orsurgical procedures.Vomiting can also cause hypokalemia, although not much potassium is lost from the vomitus. Rather, heavy urinary losses of K+ in the setting of post-emetic bicarbonaturia force urinary potassium excretion. (Seediscussion of alkalosis below.) Othergastrointestinal causes includepancreatic fistulae and the presence ofadenoma.[citation needed]
A low level of magnesium in the blood can also cause hypokalemia.Magnesium is required for adequate processing of potassium. This may become evident when hypokalemia persists despite potassium supplementation. Other electrolyte abnormalities may also be present.[citation needed]
An increase in the pH of the blood (alkalosis) can cause temporary hypokalemia by causing a shift of potassium out of theplasma andinterstitial fluids into the urine via a number of interrelated mechanisms. 1) Type Bintercalated cells in thecollecting duct reabsorb H+ and secrete HCO3, while in type A intercalated cells protons are secreted via both H+-K+ATPases and H+ ATP-ases on the apical/luminal surface of the cell. By definition, the H+-K+ATPase reabsorbs one potassium ion into the cell for every proton it secretes into the lumen of the collecting duct of a nephron. In addition, when H+ is expelled from the cell (by H+ATP-ase), cations—in this case potassium—are taken up by the cell in order to maintain electroneutrality (but not through direct exchange as with the H+-K+ATPase).[13] In order to correct the pH during alkalosis, these cells will use these mechanisms to reabsorb great amounts of H+, which will concomitantly increase their intracellular concentrations of potassium. This concentration gradient drives potassium to be secreted across the apical surface of the cell into the tubular lumen through potassium channels (this facilitated diffusion occurs in both Type B intercalated cells and Principal cells in the collecting duct). 2) Metabolic alkalosis is often present in states of volume depletion, such as vomiting, so potassium is also lost viaaldosterone-mediated mechanisms. 3) During metabolic alkalosis, the acute rise of plasmaHCO3− concentration (caused by vomiting, for example) will exceed the capacity of the renalproximal tubule to reabsorb thisanion, and potassium will be excreted as an obligatecation partner to the bicarbonate.[14]
Disease states that lead to abnormally highaldosterone levels can cause hypertension and excessive urinary losses of potassium. These includerenal artery stenosis andtumors (generally nonmalignant) of theadrenal glands, e.g.,Conn's syndrome (primaryhyperaldosteronism).Cushing's syndrome can also lead to hypokalemia due to excess cortisol binding the Na+/K+ pump and acting like aldosterone. Hypertension and hypokalemia 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 asapparent mineralocorticoid excess syndrome—can either be congenital or caused by consumption ofglycyrrhizin, which is contained in extract oflicorice, sometimes found inherbal supplements,candies, and chewing tobacco.[citation needed]
Rarehereditary defects of renal salt transporters, such asBartter syndrome orGitelman 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.[citation needed]
Rare hereditary defects of muscular ion channels and transporters that causehypokalemic periodic paralysis can precipitate occasional attacks of severe hypokalemia and muscle weakness. These defects cause a heightened sensitivity to the normal changes in potassium produced bycatecholamines and/orinsulin and/orthyroid hormone, which lead to movement of potassium from the extracellular fluid into the muscle cells.[citation needed]
A handful of published reports describe individuals with severe hypokalemia related to chronic extreme consumption (4–10 L/day) ofcola.[20] The hypokalemia is thought to be from the combination of thediuretic effect ofcaffeine[21] and copious fluid intake, although it may also be related todiarrhea caused by heavyfructose ingestion.[22][23]
Pseudohypokalemia is a decrease in the amount of potassium that occurs due to excessive uptake of potassium by metabolically active cells in a blood sample after it has been drawn. It is a laboratory artifact that may occur when blood samples remain in warm conditions for several hours before processing.[24]
Potassium is essential for many body functions, includingmuscle andnerve activity. The electrochemical gradient of potassium between the intracellular and extracellular space is essential for nerve function; in particular, potassium is needed to repolarize thecell membrane to a resting state after anaction potential has passed. Lower potassium levels in the extracellular space cause hyperpolarization of the resting membrane potential. Thishyperpolarization is caused by the effect of the altered potassium gradient onresting membrane potential as defined by theGoldman equation. As a result, a greater-than-normal stimulus is required for depolarization of the membrane to initiate an action potential.[citation needed]
In the heart, hypokalemia causes arrhythmias because of less-than-complete recovery from sodium-channel inactivation, making the triggering of an action potential less likely. In addition, the reduced extracellular potassium (paradoxically) inhibits the activity of the IKr potassium current and delays ventricular repolarization. This delayed repolarization may promotereentrant arrhythmias.[25]
Hypokalemia leads to characteristicECG changes (PR prolongation, ST-segment and T-wave depression, U-wave formation).[4]
The earliest ECG findings, associated with hypokalemia, are decreased T wave height. Then, ST depressions and T inversions appear as serum potassium levels reduce further. Due to prolonged repolarization of ventricularPurkinje fibers, prominent U waves occur (usually seen at V2 and V3 leads), frequently superimposed upon T waves, therefore producing the appearance of prolonged QT intervals, when serum potassium levels fall below 3 mEq/L.[27]
The amount of potassium deficit can be calculated using the following formula: Kdeficit (in mmol) = (Knormal lower limit − Kmeasured) × body weight (kg) × 0.4 Meanwhile, the daily body requirement of potassium is calculated by multiplying 1 mmol to body weight in kilograms. Adding potassium deficit and daily potassium requirement would give the total amount of potassium need to be corrected in mmol. Dividing mmol by 13.4 will give the potassium in grams.[28]
Treatment includes addressing the cause, such as improving the diet, treatingdiarrhea, or stopping an offending medication. People without a significant source of potassium loss and who show no symptoms of hypokalemia may not require treatment. Acutely, repletion with 10 mEq of potassium is typically expected to raise serum potassium by 0.1 mEq/L immediately after administration. However, for those with chronic hypokalemia, repletion takes time due to tissue redistribution. For example, correction by 1 mEq/L can take more than 1000 mEq of potassium over many days.[6]
Eating potassium-rich foods may not be sufficient for correcting low potassium; potassium supplements may be recommended. Potassium contained in foods is almost entirely coupled with phosphate and is thus ineffective in correcting hypokalemia associated withhypochloremia that may occur due to vomiting, diuretic therapy, or nasogastric drainage. Additionally, replacing potassium solely through diet may be costly and result in weight gain due to potentially large amounts of food needed. An effort should also be made to limit dietary sodium intake due to an inverse relationship with serum potassium. Increasing magnesium intake may also be beneficial for similar physiological reasons.[30]
Potassium chloride supplements by mouth have the advantage of containing precise quantities of potassium, but the disadvantages of a taste which may be unpleasant, and the potential for side-effects includingnausea and abdominal discomfort.Potassium bicarbonate is preferred when correcting hypokalemia associated withmetabolic acidosis.[30]
Severe hypokalemia (<3.0 mEq/L) may requireintravenous supplementation. Typically, asaline solution is used, with 20–40 meq/L KCl per liter over 3–4 hours.[31] Giving IV potassium at faster rates (20–25 meq/hr) may inadvertently expose the heart to a sudden increase in potassium, potentially causing dangerousabnormal heart rhythms such asheart block orasystole.[25] Faster infusion rates are therefore generally only performed in locations in which the heart rhythm can be continuously monitored such as acritical care unit.[31] When replacing potassium intravenously, particularly when higher concentrations of potassium are used, infusion by acentral line is encouraged to avoid the occurrence of a burning sensation at the site of infusion, or the rare occurrence ofdamage to the vein.[32] When peripheral infusions are necessary, the burning can be reduced by diluting the potassium in larger amounts of fluid, or adding a small dose of lidocaine to the intravenous fluid,[31] although adding lidocaine may increase the likelihood of medical errors.[33] Even in severe hypokalemia, oral supplementation is preferred given its safety profile. Sustained-release formulations should be avoided in acute settings.[citation needed]
Hypokalemia which is recurrent or resistant to treatment may be amenable to a potassium-sparingdiuretic, such asamiloride,triamterene,spironolactone, oreplerenone. Concomitant hypomagnesemia will inhibit potassium replacement, as magnesium is a cofactor for potassium uptake.[30]
The plot of the science fiction novelDestiny's Road byLarry Niven centers around the setting's scarcity of available potassium, and the resulting deficiency and its effects on the world's colonists and their society.[34][35][36][37]
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