Hyperkalemia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]; Raviteja Guddeti, M.B.B.S. [3];Mahmoud Sakr, M.D. [4]

Synonyms and keywords: Hyperkalaemia.

Overview

Hyperkalemia (AE) or Hyperkalaemia (BE) is an elevated blood level (above 5.0 mmol/L) of the electrolyte potassium. The prefix hyper- means high (contrast with hypo-, meaning low). The middle kal refers to kalium, which is Latin for potassium. The end portion of the word, -emia, means "in the blood". Extreme degrees of hyperkalemia are considered a medical emergency due to the risk of potentially fatal arrhythmias

Pathophysiology

Potassium is the most abundant intracellular cation. It is critically important for many physiologic 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 and the kidney.

The renal elimination of potassium is passive (through the glomeruli), and resorption 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.

Hyperkalemia develops when there is excessive production (oral intake, tissue breakdown) or ineffective elimination of potassium. Ineffective elimination can be hormonal (inaldosterone 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. This depolarization opens some voltage-gated sodium channels, but not enough to generate an action potential. After a short while, the open sodium channels inactivate and become refractory, increasing the threshold to generate an action potential. 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.

Patients with the rare hereditary condition of hyperkalemic periodic paralysis appear to have a heightened sensitivity of muscular symptoms that are associated with transient elevation of potassium levels. Episodes of muscle weakness and spasms can be precipitated by exercise or fasting in these subjects.==[[Hyperkalemia ==Risk factors

Risk Factors

The kidneys normally remove excess potassium from the body. Most cases of hyperkalemia are caused by disorders that reduce the kidneys' ability to get rid of potassium. This may result from disorders such as:

• Acute kidney failure
• Chronic kidney failure
• Glomerulonephritis
• Obstructive uropathy
• Rejection of a kidney transplant

The hormone aldosterone regulates kidney removal of sodium and potassium. Lack of aldosterone can result in hyperkalemia with an increase in total body potassium.Addison's disease is one disorder that causes reduced aldosterone production.

Any time potassium is released from the cells, it may build up in the fluid outside the cells and in the bloodstream. Acidosis leads to the movement of potassium from inside the cells to the fluid outside the cells. Tissue injury can cause the cells to release potassium. Such injury includes:

• Burns
• Disorders that cause blood cells to burst (hemolytic conditions)
• Gastrointestinal bleeding
• Rhabdomyolysis from drugs, alcoholism, coma, or certain infections
• Surgery
• Traumatic injury
• Tumors

If the kidney is working properly, and there is enough aldosterone, tissue trauma alone rarely leads to hyperkalemia. A normally functioning kidney will remove the excess potassium that has been released from the cells.

Increased intake of potassium can cause hyperkalemia if kidney function is poor. Salt substitutes often contain potassium, as do many "low-salt" packaged foods.

Hyperkalemia may be caused by medications, including medications that affect kidney function (potassium sparing diuretics, such as spironolactone, amiloride, ortriamterene) and potassium supplements (especially intravenous potassium).

Causes

Common Causes

• ACE inhibitors
• Acidosis
• Addisonian crisis
• Beta blockers
• Blood transfusion and complications
• Cirrhosis
• Diabetic nephropathy
• Increased ingestion of high potassium foods
• Malnutrition
• Renal tubular acidosis
• Renal failure

Causes by Organ System

Cardiovascular	Heart failure, Volume depletion
Chemical / poisoning	Ammonium Bifluoride, Arsenicals, Fluoride toxicity, Foxglove Poisoning, Oleander Poisoning, Tungsten, White ChameleonPoisoning
Dermatologic	No underlying causes
Drug Side Effect	ACE inhibitors, Acetylsalicylic Acid, Aldosterone antagonists, Amiloride, Angiotensin receptor blockers, Beta blockers,Celecoxib, Cyclosporine, Diazoxide, Digoxin, Eplerenone, Epsilon amino caproic acid (EACA), Erythropoietin, Heparin, Ibuprofen,Indomethacin, Isoflurane, Ketoprofen, Low-molecular weight heparin, Mannitol, Melarsoprol, Methotrexate, Minoxidil, Naproxen,Pancuronium bromide, Pimecrolimus, Potassium chloride, Potassium citrate, Propofol infusion syndrome, Sodium thiopental, Somatostatin therapy,Spironolactone, Succinylcholine, Suxamethonium, Tacrolimus, Triamterene, Trimethoprim
Ear Nose Throat	No underlying causes
Endocrine	ACTH Deficiency, Addisonian crisis, Addison's disease, Adrenal gland disorders, Adrenal hyperplasia, congenital type 3, Autoimmune adrenalitis, Congenital adrenal hyperplasia -- sodium-wasting form, Diabetes, Diabetic ketoacidosis, Hyperglycemia, Hypoadrenocorticism --hypoparathyroidism -- moniliasis, Hyporeninemic hypoaldosteronism, Isolated aldosterone synthase deficiency, Lipoid congenital adrenal hyperplasia,Pseudohypoaldosteronism type 1, Pseudohypoaldosteronism type 2
Environmental	No underlying causes
Gastroenterologic	Cirrhosis, Gastrointestinal bleeding
Genetic	18-Hydroxylase deficiency, Congenital adrenal hyperplasia type 3, Congenital adrenal hyperplasia -- sodium-wasting form, Isolated aldosterone synthase deficiency, Lipoid congenital adrenal hyperplasia, Pseudohypoaldosteronism type 1, Pseudohypoaldosteronism type 2
Hematologic	Hemolytic anemia, Leukaemia, Leukocytosis, Sickle cell disease, Thrombotic thrombocytopenic purpura, congenital
Iatrogenic	Oxalate blood sample, Blood transfusion and complications, Cuffed blood sample, Delayed separation blood sample, Drip arm sample,EDTA blood sample, Hemolysed blood sample, IV fluids containing potassium, Using clenched fist while collection of blood
Infectious Disease	HIV infection
Musculoskeletal / Ortho	Muscle damage, Muscle wasting
Neurologic	Amelo-cerebro-hypohidrotic syndrome, Kohlschutter-Tonz syndrome
Nutritional / Metabolic	Arginine hydrochloride, Increased ingestion of high Potassium foods, Increased ingestion of Potassium containing drugs, Malnutrition
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Opthalmologic	No underlying causes
Overdose / Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal / Electrolyte	Acidosis, Acute glomerulonephritis, Acute renal failure, Chronic Interstitial nephritis, Chronic renal failure, Diabetic nephropathy, Distal chloride shunt, Distal renal tubular acidosis type IV, Gordon's syndrome, Hemolytic uremic syndrome, Hyperkalemic periodic paralysis, Hyperkalemic Renal tubular acidosis, Hypernatremia, Hyperosmolality, Hyperphosphataemia, Lupus nephritis, Obstructive uropathy,Polycystic kidney disease, Familial Pseudohyperkalemia-due to red cell leak, Distal Renal tubular acidosis type 1, Transplanted kidneys, Tubulointerstitial disease, Urinary tract obstruction, Urolithiasis, Hyporeninemic hypoaldosteronism, Amyloidosis - Renal
Rheum / Immune / Allergy	Systemic lupus erythematosus, Autoimmune adrenalitis
Sexual	No underlying causes
Trauma	Crush syndrome
Urologic	No underlying causes
Dental	No underlying causes
Miscellaneous	Amyloidosis - Renal, Burns, Dehydration, Fasting, Hypothermia, Internal bleeding, Intravenous infusion, hyperpyrexia, Phlebotomy complication, Rhabdomyolysis, Sea snake poisoning, Selective impairment of potassium excretion, exercise,Transplant rejection, Tumor lysis syndrome, Ureterojejunostomy

Causes in Alphabetical Order

Acidosis ACTH Deficiency Acute glomerulonephritis Acute renal failure Addisonian crisis Addison's disease Adrenal gland disorders Adrenal hyperplasia, congenital-type 3 Aldosterone antagonists Amelo-cerebro-hypohidrotic syndrome Amiloride Ammonium Bifluoride Amyloidosis - Renal Angiotensin receptor blockers Arginine hydrochloride Arsenicals Autoimmune adrenalitis Beta blockers Blood transfusion and complications Burns Celecoxib Chronic interstitial nephritis Chronic renal failure Cirrhosis Congenital adrenal hyperplasia -- sodium-wasting form Crush syndrome Cuffed blood sample Cyclosporine Dehydration Delayed separation blood sample Diabetes Diabetic ketoacidosis Diabetic nephropathy Diazoxide Digoxin Distal chloride shunt Drip arm sample EDTA blood sample Eplerenone Epsilon amino caproic acid (EACA) Erythropoietin Fasting Fluoride toxicity Foxglove poisoning Gastrointestinal bleeding Gordon's syndrome Heart failure Hemolysed blood sample Hemolytic anemia Hemolytic uremic syndrome Heparin HIV infection Hyperglycemia Hyperkalemic periodic paralysis Hyperkalemic Renal tubular acidosis Hypernatremia Hyperosmolality Hyperphosphataemia Hypoadrenocorticism -- hypoparathyroidism -- moniliasis Hyporeninemic hypoaldosteronism Hypothermia Ibuprofen Increased ingestion of high potassium foods Increased ingestion of potassium containing drugs

Indomethacin Internal bleeding Intravenous infusion Isoflurane Isolated aldosterone synthase deficiency IV fluids containing Potassium Ketoprofen Kohlschutter-Tonz syndrome Leukaemia Leukocytosis Lipoid congenital adrenal hyperplasia Low-molecular weight heparin Lupus nephritis Malignant hyperpyrexia Malnutrition Mannitol Melarsoprol Methotrexate Minoxidil Muscle damage Muscle wasting Naproxen Obstructive uropathy Oleander Poisoning Oxalate blood sample Pancuronium bromide Phlebotomy complication Pimecrolimus Polycystic kidney disease Potassium chloride Potassium citrate Propofol infusion syndrome Pseudohyperkalaemia, familial, due to red cell leak Pseudohypoaldosteronism type 1 Pseudohypoaldosteronism type II Pyrimidifen Renal tubular acidosis, distal-type 1 Renal tubular acidosis, distal-type 4 Rhabdomyolysis Sea snake poisoning Selective impairment of potassium excretion Sickle cell disease Sodium thiopental Somatostatin therapy Spironolactone Strenuous exercise Succinylcholine Suxamethonium Systemic lupus erythematosus Tacrolimus Thrombotic thrombocytopenic purpura-congenital Thrombocytosis Transplant rejection Transplanted kidneys Triamterene Trimethoprim Tubulointerstitial disease Tumor lysis syndrome Tungsten Ureterojejunostomy Urinary tract obstruction Urolithiasis Using clenched fist while collection of blood Volume depletion White Chameleon poisoning

History

A detailed history taking is very helpful in diagnosing the cause of hyperkalemia.

• Dietary history (diets with low sodium and rich in potassium)
  • Diets recommended for patients with cardiac disease, hypertension, and diabetes mellitus
  • Potassium supplements in herbal supplements, salt substitutes
  • Fruits, dried fruits, juices, banana and vegetables

• Medications history (drugs causing a decreased excretion of potassium)
  • Nonsteroidal anti-inflammatory drugs
  • Angiotensin-converting enzyme inhibitors
  • Angiotensin receptor blockers (potassium-sparing diuretics, especially popular in the treatment of cirrhosis and congestive heart failure)
  • Cyclosporine or tacrolimus
  • Antibiotics, such as pentamidine or trimethoprim/sulfamethoxazole

• Medical history
  • Renal failure
  • Diabetes mellitus
  • Sickle cell disease or trait
  • Urinary tract obstruction - Type IV renal tubular acidosis, also called hyperkalemic renal tubular acidosis. It can be seen with polycystic kidney disease,amyloidosis and diabetes mellitus.
  • The combination of abdominal pain, hypoglycemia and hyperpigmentation, often in the context of a history of other autoimmune disorders, may be signs of Addison's disease, itself a medical emergency.

Symptoms

Hyperkalemia often has no symptoms and the problem may be detected during screening blood tests for another medical disorder, or it may only come to medical attention after complications have developed, such as cardiac arrhythmia or sudden death. Patients may present with the symptoms such as, irregular heartbeat, nausea, slow, weak, or absent pulse. Extreme degrees of hyperkalemia are considered a medical emergency due to the risk of potentially fatalarrhythmias. Symptoms are fairly nonspecific and may include:

• Malaise
• Palpitations
• Muscle weakness
• Mild breathlessness may indicate metabolic acidosis, one of the settings in which hyperkalemia may occur.

Physical Examination

Vitals

Pulse

• Bradycardia (heart block)

Respiratory Rate

• Tachypnea (respiratory muscle weakness)

Neurologic

• Muscle weakness
• Flaccid paralysis
• Depressed or absent deep tendon reflexes
• Muscle tenderness associated with muscle weakness (rhabdomyolysis)

Laboratory Findings

Initial

• Calcium
• Phosphate
• Magnesium
• Blood urea nitrogen (BUN)/creatinine

Extensive Evaluation

• Cortisol
• Renin
• Aldosterone levels
• Transtubular potassium gradient (by assessing potassium+ secretion)

Electrocardiogram

There appears to be a direct effect of elevated potassium on some of the potassium channels that increases their activity and speeds membrane repolarization. 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.

Moderate Hyperkalemia

With moderate hyperkalemia, there is reduction of the size of the P wave and development of tent-shaped T waves.

Severe Hyperkalemia

Further hyperkalemia will lead to widening of the QRS complex, and the QRS complex may ultimately become sinusoidal in shape (sine wave pattern).

EKG Examples

The EKG below demonstrates Peaked T waves of hyperkalemia.

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The EKG below demonstrates characteristics of hyperkalemia including: Broad QRS complexes circled in green; fusion of the QRS complex and the Twave as circled in blue; and tall peaked T waves as circled in red.

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Tall, Narrow, and Peaked T waves

• Earliest sign of hyperkalemia
• Occurs with K > 5.5 meq/li
• Differential diagnosis of this EKG change includes the T wave changes of bradycardia or stroke.
• Prominent U waves and QTc prolongation are more consistent with stroke than hyperkalemia.

Shown below is the EKG demonstrating Tall, narrow and peaked T waves:

Shown below is the EKG demonstrating Tall, narrow and peaked T waves:

Intraventricular Conduction Defect

• Observed when K > 6.5 meq/li
• There is a modest correlation of the QRS duration with serum K
• As the K rises, the QRS complexes may resemble sine waves
• Generally the widening is diffuse and usually there is no resemblance of the morphology to that of either LBBB or RBBB

Intraventricular Conduction Defect on EKG Before and After Treatment for Hyperkalemia

Shown below are the series of EKG images before, during and after treatment:

Before Treatment

During Treatment

After Treatment

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Decrease of the Amplitude of the P wave or an Absent P Wave

• Decreased P wave amplitude occurs when the K is > 7.0 meq/li
• P waves may be absent when the K is > 8.8 meq/li
• The impulses are still being generated in the SA node and are conducted to the ventricles through specialized atrial fibers without depolarizing the atrial muscle
• Moderate or sever hyperkalemia can cause sinus arrest

ST Segment Changes Simulating Current of Injury

• Have been labeled the dialyzable current of injury

Cardiac arrhythmias: bradyarrhythmias, tachyarrhythmias, atrioventricular conduction defects

• Occurs with severe hyperkalemia, not mild to moderate hyperkalemia

Medical Therapy

• Calcium supplementation (calcium gluconate 10% (10ml), preferably through a central venous catheter as the calcium may cause phlebitis) does not lower potassium but decreases myocardial excitability, protecting against life threatening arrhythmias.
• Insulin (e.g. intravenous injection of 10-15u of (short acting) insulin (e.g. Actrapid) {along with 50ml 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.
• Bicarbonate therapy (e.g. 1 ampule (45mEq) infused over 5 minutes) is effective in cases of metabolic acidosis. The bicarbonate ion will stimulate an exchange of cellular H⁺ for Na⁺, thus leading to stimulation of the sodium-potassium ATPase.
• Salbutamol (albuterol, Ventolin^®) is a β₂-selective catacholamine that is administered by nebuliser (e.g. 10-20 mg). This drug promotes movement of K into cells, lowering the blood levels.
• Polystyrene sulfonate (Calcium Resonium, Kayexalate) is a binding resin that binds K within the intestine and removes it from the body by defecation. Calcium Resonium (15g three times a day in water) can be given by mouth. Kayexelate can be given by mouth or as an enema. In both cases, the resin absorbs K within the intestine and carries it out of the body by defecation. This medication may cause diarrhea.
• Refractory or severe cases may need dialysis to remove the potassium from the circulation.
• Preventing recurrence of hyperkalemia typically involves reduction of dietary potassium, removal of an offending medication, and/or the addition of a diuretic (such asfurosemide (Lasix^®) or hydrochlorothiazide).