|Classification and external resources|
Hyperkalemia (hyperkalaemia in British English, hyper- high; kalium, potassium; -emia, "in the blood") refers to the condition in which the concentration of the electrolyte potassium (K+) in the blood is elevated. The symptoms of elevated potassium are nonspecific, and the condition is usually discovered on blood tests performed for another reason. Extreme hyperkalemia is a medical emergency due to the risk of potentially fatal abnormal heart rhythms (arrhythmia).
- 1 Signs and symptoms
- 2 Causes
- 3 Pathophysiology
- 4 Diagnosis
- 5 Prevention
- 6 Treatment
- 7 References
- 8 External links
Signs and symptoms
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Symptoms are fairly nonspecific and generally include malaise, palpitations and muscle weakness; mild 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.
During the medical-history intake, physicians focus on kidney disease and medication use (see below), as these are the main causes. The combination of abdominal pain, hypoglycemia, and hyperpigmentation, often in the context of other autoimmune disorders, may be signs of Addison's disease, which is a medical emergency.
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- Renal insufficiency
- Medication that interferes with urinary excretion:
- Mineralocorticoid deficiency or resistance, such as:
- 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
- Rhabdomyolysis, burns or any cause of rapid tissue necrosis, including tumor lysis syndrome
- Massive blood transfusion or massive hemolysis
- Shifts/transport out of cells caused by acidosis, low insulin levels, beta-blocker therapy, digoxin overdose, or the paralyzing agent succinylcholine
- Box jellyfish venom
- Digoxin toxicity decreases sodium potassium ATPase activity preventing potassium from entering cells.[unreliable medical source?]
- Excessive intake with salt-substitute, potassium-containing dietary supplements, or potassium chloride (KCl) infusion. Note that, for a person with normal kidney function and normal elimination (see above), hyperkalemia by potassium intake would be seen only with large infusions of KCl or oral doses of several hundred milliequivalents of KCl.[unreliable medical source?]
Pseudohyperkalemia is a rise in the amount of potassium that occurs due to excessive leakage of potassium from cells, during or after blood is drawn. It is a laboratory artifact rather than a biological abnormality and can be misleading to caregivers.[unreliable medical source?] Pseudohyperkalemia is typically caused by hemolysis during venipuncture (by either excessive vacuum of the blood draw or by a collection needle that is of too fine a gauge); excessive tourniquet time or fist clenching during phlebotomy (which presumably leads to efflux of potassium from the muscle cells into the bloodstream);[unreliable medical source?] or by a delay in the processing of the blood specimen. It can also occur in specimens from patients with abnormally high numbers of platelets (>500,000/mm³), leukocytes (> 70 000/mm³), or erythrocytes (hematocrit > 55%). People with "leakier" cell membranes have been found, whose blood must be separated immediately to avoid pseudohyperkalemia.[unreliable medical source?]
A familial form of pseudohyperkalemia occurs, which is a dominant red-cell trait characterized by increased serum potassium in whole blood stored at or below room temperature, without additional hematological abnormalities.[unreliable medical source?] It appears to be due to mutations in Langereis blood group antigen, which encodes an erythrocyte membrane porphyrin transporter. The gene, known as ABCB6, is located on the long arm of chromosome 2 (2q36).
Normal serum potassium levels are between 3.5 and 5.0 mEq/L. 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.
Its main dietary sources are vegetables (tomato and potato), fruits (orange and banana) and meat. Elimination is through the gastrointestinal tract, kidney and sweat glands. The renal 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.
Hyperkalemia develops when there is excessive production (oral intake, tissue breakdown) or ineffective elimination of potassium. Ineffective elimination can be hormonal (in aldosterone deficiency) or due to causes in the renal parenchyma 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 result in ventricular fibrillation or asystole.
During extreme exercise, potassium is released from active muscle, and the serum potassium rises to a point that would be dangerous at rest. 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.
Patients with the rare hereditary condition of hyperkalemic periodic paralysis appear to have a heightened muscular sensitivity that is associated with transient elevation of potassium levels. Episodes of muscle weakness and spasms can be precipitated by exercise or fasting in these subjects.
To gather enough information for diagnosis, the measurement of potassium needs to 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 mEq/L. Generally, blood tests for renal function (creatinine, blood urea nitrogen), glucose and occasionally creatine kinase and cortisol will be performed. Calculating the trans-tubular potassium gradient can sometimes help in distinguishing the cause of the hyperkalemia.
With mild to moderate hyperkalemia, there is reduction of the size of the P wave and development of peaked T waves. Severe hyperkalemia results in a widening of the QRS complex, and the ECG complex can evolve to a sinusoidal shape. There appears to be a direct effect of elevated potassium on some of the potassium channels that increases their activity and speeds membrane repolarization. Also, (as noted above), hyperkalemia causes an overall membrane depolarization that inactivates many sodium channels. The faster repolarization of the cardiac action potential causes the tenting of the T waves, and the inactivation of sodium channels causes a sluggish conduction of the electrical wave around the heart, which leads to smaller P waves and widening of the QRS complex.
The serum potassium concentration at which electrocardiographic changes develop is somewhat variable. Although the factors influencing the effect of serum potassium levels on cardiac electrophysiology are not entirely understood, the concentrations of other electrolytes, as well as levels of catecholamines, play a major role.
ECG findings are not a reliable finding in hyperkalemia. In retrospective review, blinded cardiologists documented peaked T-waves in only 3 of 90 ECGs with hyperkalemia. Sensitivity of peaked-Ts for hyperkalemia ranged from 0.18 to 0.52 depending on the criteria for peak-T waves.
Preventing recurrence of hyperkalemia typically involves reduction of dietary potassium, removal of an offending medication, and/or the addition diuretic (such as furosemide or hydrochlorothiazide). Sodium polystyrene sulfonate and sorbital (combined as Kayexalate) are occasionally used on an ongoing basis to maintain lower serum levels of potassium. Concerns regarding its use are noted in the previous section.
When arrhythmias occur, or when potassium levels exceed 6.5 mmol/l, emergency lowering of potassium levels is mandated. Several agents are used to transiently lower K+ levels. Choice depends on the degree and cause of the hyperkalemia, and other aspects of the patient's condition.
Calcium (calcium chloride or calcium gluconate) increases threshold potential through a mechanism that is still unclear, thus restoring normal gradient between threshold potential and resting membrane potential, which is elevated abnormally in hyperkalemia. A standard ampule of 10% calcium chloride is 10 mL and containe 6.8 mmol of calcium. A standard ampule of 10% calcium gluconate is also 10 mL but has only 2.26 mmol of calcium. Clinical practice guidelines recommend giving 6.8 mmol for typical EKG findings of hyperkalemia. This is 10 mL of 10% calcium chloride or 30 mL of 10% calcium gluconate. Though calcium chloride is more concentrated, it is caustic to the veins and should only be given through a central line. Onset of action is less than five minutes and lasts about 30-60 min. The goal of treatment is to normalize the EKG and doses can be repeated if the EKG does not improve in 3 minutes.
Some textbooks suggest that calcium should not be given in digoxin toxicity as it has been linked to cardiovascular collapse in humans and increased digoxin toxicity in animal models. Recent literature questions if this is a real concern.
Several medical treatments shift potassium ions from the bloodstream into the cellular compartment, thereby reducing the risk of complications. The effect of these measures tends to be short-lived, but may temporize the problem until potassium can be removed from the body.
- Insulin (e.g. intravenous injection of 10-15 units of regular insulin along with 50 ml of 50% dextrose to prevent hypoglycemia) will lead to a shift of potassium ions into cells, secondary to increased activity of the sodium-potassium ATPase. Its effects last a few hours, so it sometimes needs to be repeated while other measures are taken to suppress potassium levels more permanently. The insulin is usually given with an appropriate amount of glucose in order to prevent hypoglycemia following the insulin administration.
- Salbutamol (albuterol, Ventolin), a β2-selective catecholamine, is administered by nebulizer (e.g. 10–20 mg). This drug also lowers blood levels of K+ by promoting its movement into cells.
- Though previously recommended, IV bicarbonate as a method to shift potassium into cells is no longer recommended. Not only has it not been effective in controlled trials but it lowers ionized calcium levels, theoretically increasing the risk of cardiac arrhythmia.
Severe cases require hemodialysis or hemofiltration, which are the most rapid methods of removing potassium from the body. These are typically used if the underlying cause cannot be corrected swiftly while temporizing measures are instituted or there is no response to these measures.
Potassium can be trapped by binding agents within the bowel. The only product approved by the FDA to treat hyperkalemia is sodium polystyrene sulfonate with sorbitol (Kayexalate), which can be given either orally or rectally to lower potassium over several hours. Removal of potassium is assumed to require defecation. However, careful clinical trials to demonstrate the effectiveness of sodium polystyrene are lacking, and use of sodium polystyrene sulfonate, particularly if formulated with high sorbitol content, is uncommonly but convincingly associated with colonic necrosis. ZS-9 is an investigational selective oral sorbent which traps potassium in the gastrointestinal tract.
Fludrocortisone, a synthetic mineralocorticoid, can also increase renal potassium excretion in patients with functioning kidneys. Trials of fludrocortisone in patients on dialysis have shown it to be ineffective.
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- "High potassium (hyperkalemia) Causes - Symptoms". Mayo Clinic. 2011-11-18. Retrieved 2014-02-28.
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- USDA National Nutrient Database for Standard Reference, Release 26
- List of foods rich in potassium
- National Kidney Foundation site on potassium content of foods