hyperkalemia hyperkalemia hyperkalemia is an elevated level of potassium (k+) in the blood. normal potassium levels are between 3.5 and 5.0 mmol/l (3.5 and 5.0 meq/l) with levels above 5.5 mmol/l defined as hyperkalemia. typically hyperkalemia does not cause symptoms. occasionally when severe it can cause palpitations, muscle pain, muscle weakness, or numbness. hyperkalemia can cause an abnormal heart rhythm which can result in cardiac arrest and death. hyperkalemiaother nameshyperkalaemiaelectrocardiography showing precordial leads in hyperkalemia.pronunciation/ˌhaɪpərkeɪˈliːmiə/ specialtycritical care medicine, nephrologysymptomspalpitations, muscle pain, muscle weakness, numbnesscomplicationscardiac arrestcauseskidney failure, hypoaldosteronism, rhabdomyolysis, certain medicationsdiagnostic methodblood potassium > 5.5 mmol/l, electrocardiogramdifferential diagnosispseudohyperkalemiatreatmentmedications, low potassium diet, hemodialysismedicationcalcium gluconate, dextrose with insulin, salbutamol, sodium bicarbonatefrequency~2% (people in hospital) common causes of hyperkalemia include kidney failure, hypoaldosteronism, and rhabdomyolysis. a number of medications can also cause high blood potassium including spironolactone, nsaids, and angiotensin converting enzyme inhibitors. the severity is divided into mild (5.5–5.9 mmol/l), moderate (6.0–6.4 mmol/l), and severe (>6.5 mmol/l). high levels can be detected on an electrocardiogram (ecg). pseudohyperkalemia, due to breakdown of cells during or after taking the blood sample, should be ruled out. initial treatment in those with ecg changes is salts, such as calcium gluconate or calcium chloride. other medications used to rapidly reduce blood potassium levels include insulin with dextrose, salbutamol, and sodium bicarbonate. medications that might worsen the condition should be stopped and a low potassium diet should be started. measures to remove potassium from the body include diuretics such as furosemide, potassium-binders such as polystyrene sulfonate and sodium zirconium cyclosilicate, and hemodialysis. hemodialysis is the most effective method. hyperkalemia is rare among those who are otherwise healthy. among those who are hospitalized, rates are between 1% and 2.5%. it is associated with an increased mortality, whether due to hyperkalaemia itself or as a marker of severe illness, especially in those without chronic kidney disease. the word hyperkalemia comes from hyper- 'high' + kalium 'potassium' + -emia 'blood condition'. signs and symptoms the symptoms of an elevated potassium level are generally few and nonspecific. nonspecific symptoms may include feeling tired, numbness and weakness. occasionally palpitations and shortness of breath may occur. hyperventilation may indicate a compensatory response to metabolic acidosis, which is one of the possible causes of hyperkalemia. often, however, the problem is detected during screening blood tests for a medical disorder, or after hospitalization for complications such as cardiac arrhythmia or sudden cardiac death. high levels of potassium (> 5.5 mmol/l) have been associated with cardiovascular events. causes ineffective elimination decreased kidney function is a major cause of hyperkalemia. this is especially pronounced in acute kidney injury where the glomerular filtration rate and tubular flow are markedly decreased, characterized by reduced urine output. this can lead to a dramatically elevated potassium in conditions of increased cell breakdown as the potassium is released from the cells and cannot be eliminated in the kidney. in chronic kidney disease, hyperkalemia occurs as a result of reduced aldosterone responsiveness and reduced sodium and water delivery in distal tubules. medications that interfere with urinary excretion by inhibiting the renin–angiotensin system is one of the most common causes of hyperkalemia. examples of medications that can cause hyperkalemia include ace inhibitors, angiotensin receptor blockers, non-selective beta blockers, and calcineurin inhibitor immunosuppressants such as ciclosporin and tacrolimus. for potassium-sparing diuretics, such as amiloride and triamterene; both the drugs block epithelial sodium channels in the collecting tubules, thereby preventing potassium excretion into urine. spironolactone acts by competitively inhibiting the action of aldosterone. nsaids such as ibuprofen, naproxen, or celecoxib inhibit prostaglandin synthesis, leading to reduced production of renin and aldosterone, causing potassium retention. the antibiotic trimethoprim and the antiparasitic medication pentamidine inhibits potassium excretion, which is similar to mechanism of action by amiloride and triamterene. mineralocorticoid (aldosterone) deficiency or resistance can also cause hyperkalemia. primary adrenal insufficiency are: addison's disease and congenital adrenal hyperplasia (cah) (including enzyme deficiencies such as 21α hydroxylase, 17α hydroxylase, 11β hydroxylase, or 3β dehydrogenase). type iv renal tubular acidosis (aldosterone resistance of the kidney's tubules) gordon's syndrome (pseudohypoaldosteronism type ii) ("familial hypertension with hyperkalemia"), a rare genetic disorder caused by defective modulators of salt transporters, including the thiazide-sensitive na-cl cotransporter. excessive release from cells metabolic acidosis can cause hyperkalemia as the elevated hydrogen ions in the cells can displace potassium, causing the potassium ions to leave the cell and enter the bloodstream. however, in respiratory acidosis or organic acidosis such as lactic acidosis, the effect on serum potassium are much less significant although the mechanisms are not completely understood. insulin deficiency can cause hyperkalemia as the hormone insulin increases the uptake of potassium into the cells. hyperglycemia can also contribute to hyperkalemia by causing hyperosmolality in extracellular fluid, increasing water diffusion out of the cells and causes potassium to move alongside water out of the cells also. the co-existence of insulin deficiency, hyperglycemia, and hyperosmolality is often seen in those affected by diabetic ketoacidosis. apart from diabetic ketoacidosis, there are other causes that reduce insulin levels such as the use of the medication octreotide, and fasting which can also cause hyperkalemia. increased tissue breakdown such as rhabdomyolysis, burns, or any cause of rapid tissue necrosis, including tumor lysis syndrome can cause the release of intracellular potassium into blood, causing hyperkalemia. beta2-adrenergic agonists act on beta-2 receptors to drive potassium into the cells. therefore, beta blockers can raise potassium levels by blocking beta-2 receptors. however, the rise in potassium levels is not marked unless there are other co-morbidities present. examples of drugs that can raise the serum potassium are non-selective beta-blockers such as propranolol and labetalol. beta-1 selective blockers such as metoprolol do not increase serum potassium levels. exercise can cause a release of potassium into bloodstream by increasing the number of potassium channels in the cell membrane. the degree of potassium elevation varies with the degree of exercise, which range from 0.3 meq/l in light exercise to 2 meq/l in heavy exercise, with or without accompanying ecg changes or lactic acidosis. however, peak potassium levels can be reduced by prior physical conditioning and potassium levels are usually reversed several minutes after exercise. high levels of adrenaline and noradrenaline have a protective effect on the cardiac electrophysiology because they bind to beta 2 adrenergic receptors, which, when activated, extracellularly decrease potassium concentration. hyperkalemic periodic paralysis is an autosomal dominant clinical condition where there is a mutation in gene located at 17q23 that regulates the production of protein scn4a. scn4a is an important component of sodium channels in skeletal muscles. during exercise, sodium channels would open to allow influx of sodium into the muscle cells for depolarization to occur. but in hyperkalemic periodic paralysis, sodium channels are slow to close after exercise, causing excessive influx of sodium and displacement of potassium out of the cells. rare causes of hyperkalemia are discussed as follows. acute digitalis overdose such as digoxin toxicity may cause hyperkalemia through the inhibition of sodium-potassium-atpase pump. massive blood transfusion can cause hyperkalemia in infants due to leakage of potassium out of the red blood cells during storage. giving succinylcholine to people with conditions such as burns, trauma, infection, prolonged immobilisation can cause hyperkalemia due to widespread activation of acetylcholine receptors rather than a specific group of muscles. arginine hydrochloride is used to treat refractory metabolic alkalosis. the arginine ions can enter cells and displace potassium out of the cells, causing hyperkalemia. calcineurin inhibitors such as cyclosporine, tacrolimus, diazoxide, and minoxidil can cause hyperkalemia. box jellyfish venom can also cause hyperkalemia. excessive intake excessive intake of potassium is not a primary cause of hyperkalemia because the human body usually can adapt to the rise in the potassium levels by increasing the excretion of potassium into urine through aldosterone hormone secretion and increasing the number of potassium secreting channels in kidney tubules. acute hyperkalemia in infants is also rare even though their body volume is small, with accidental ingestion of potassium salts or potassium medications. hyperkalemia usually develops when there are other co-morbidities such as hypoaldosteronism and chronic kidney disease. pseudohyperkalemia pseudohyperkalemia occurs when the measured potassium level is falsely elevated. this condition is usually suspected when the patient is clinically well without any ecg changes. mechanical trauma during blood drawing can cause potassium leakage out of the red blood cells due to haemolysis of the blood sample. repeated fist clenching during the blood draw can cause a transient rise in potassium levels. prolonged length of blood storage can also increase serum potassium levels. hyperkalemia may become apparent when a person's platelet concentration is more than 500,000/microl in a clotted blood sample (serum blood sample). potassium leaks out of platelets after clotting has occurred. a high white cell count (greater than 120,000/microl) in people with chronic lymphocytic leukemia increases the fragility of red blood cells, thus causing pseudohyperkalemia during blood processing. this problem can be avoided by processing serum samples, because clot formation protects the cells from haemolysis during processing. a familial form of pseudohyperkalemia, a benign condition characterised by increased serum potassium in whole blood stored at cold temperatures, also exists. this is due to increased potassium permeability in red blood cells. mechanism physiology potassium is the most abundant intracellular cation and about 98% of the body's potassium is found inside cells, with the remainder in the extracellular fluid including the blood. membrane potential is maintained principally by the concentration gradient and membrane permeability to potassium with some contribution from the na+/k+ pump. the potassium gradient is critically important for many physiological processes, including maintenance of cellular membrane potential, homeostasis of cell volume, and transmission of action potentials in nerve cells. potassium is eliminated from the body through the gastrointestinal tract, kidney and sweat glands. in the kidneys, elimination of potassium is passive (through the glomeruli), and reabsorption is active in the proximal tubule and the ascending limb of the loop of henle. there is active excretion of potassium in the distal tubule and the collecting duct; both are controlled by aldosterone. in sweat glands potassium elimination is quite similar to the kidney, its excretion is also controlled by aldosterone. regulation of serum potassium is a function of intake, appropriate distribution between intracellular and extracellular compartments, and effective bodily excretion. in healthy individuals, homeostasis is maintained when cellular uptake and kidney excretion naturally counterbalance a patient's dietary intake of potassium. when kidney function becomes compromised, the ability of the body to effectively regulate serum potassium via the kidney declines. to compensate for this deficit in function, the colon increases its potassium secretion as part of an adaptive response. however, serum potassium remains elevated as the colonic compensating mechanism reaches its limits. elevated potassium hyperkalemia develops when there is excess production (oral intake, tissue breakdown) or ineffective elimination of potassium. ineffective elimination can be hormonal (in aldosterone deficiency) or due to causes in the kidney that impair excretion. increased extracellular potassium levels result in depolarization of the membrane potentials of cells due to the increase in the equilibrium potential of potassium. this depolarization opens some voltage-gated sodium channels, but also increases the inactivation at the same time. since depolarization due to concentration change is slow, it never generates an action potential by itself; instead, it results in accommodation. above a certain level of potassium the depolarization inactivates sodium channels, opens potassium channels, thus the cells become refractory. this leads to the impairment of neuromuscular, cardiac, and gastrointestinal organ systems. of most concern is the impairment of cardiac conduction, which can cause ventricular fibrillation and/or abnormally slow heart rhythms. diagnosis an ecg of a person with a potassium of 5.7 showing large t waves and small p waves to gather enough information for diagnosis, the measurement of potassium must be repeated, as the elevation can be due to hemolysis in the first sample. the normal serum level of potassium is 3.5 to 5 mmol/l. generally, blood tests for kidney function (creatinine, blood urea nitrogen), glucose and occasionally creatine kinase and cortisol are performed. calculating the trans-tubular potassium gradient can sometimes help in distinguishing the cause of the hyperkalemia. also, electrocardiography (ecg) may be performed to determine if there is a significant risk of abnormal heart rhythms. physicians taking a medical history may focus on kidney disease and medication use (e.g. potassium-sparing diuretics), both of which are known causes of hyperkalemia. definitions normal serum potassium levels are generally considered to be between 3.5