Hypokalemia

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Hypokalemia Definition

Hypokalemia is an imbalance in metabolism, where the serum potassium (K+) concentration is low (hypo means- low, kalium- potassium, emia- in blood). Potassium amount < 2.5 mmol/L may be life-threatening, and will require urgent medical attention.

Nearly 95% of the total potassium in the body is found intracellular, whereas, the remaining amount is found in the blood. Na+/K+ pump maintains this concentration gradient. Hypokalemia can either be a disease symptom, or diuretic drug side effect. Normally, hormone insulin secretion stimulated by food is capable of preventing diet-induced hypokalemia that occurs temporarily, thereby increasing the absorption of potassium by the cells.

Thus, in hypokalemia, there occurs an imbalance, as a result of dysfunction of the normal above-mentioned process, or due to loss of sweat or urine rapidly without being able to replace the lost potassium.

  • Normal serum potassium– 3.5-5.5 mEq/L
  • Normal plasma potassium– 3.5-5.0 mEq/L

Hypokalemia Epidemiology

  • Nearly five people being hospitalized in the US, has low serum potassium level.
  • People with anorexia nervosa and bulimia, AIDS, alcoholics, and having past history of bariatric surgery have chances of getting hypokalemia more than the other population.

Hypokalemia Synonyms

  • Hypokalemic Syndrome
  • Low Potassium Syndrome
  • Hypopotassemia Syndrome
  • Potassium Loss Syndrome
  • Nephritis, Potassium-Losing

Potassium Benefits

  • Potassium, primarily found in the bone and skeletal muscle, combines with sodium to contribute in the flowing of body fluids from one cell to the other.
  • It helps in the protein functioning and muscle contraction, including heart muscles.
  • The cardiac muscles need potassium for regulating blood pressure, and maintaining normal heartbeats.
  • Potassium concentration is regulated and maintained by the kidneys via urine excretion.
  • Normal kidneys utilize the potassium attained from diet, and excrete the excess potassium through sweat and urine.
  • Hormones like aldosterone regulate the balance of potassium as well.
  • It co-regulates the adenosine triphosphate along with sodium.

Hypokalemia Pathophysiology

Increased levels of potassium in the ECF causes resting membrane potential’s hyperpolarization, as a result of the altered potassium gradient of the resting membrane potential; the Goldman equation defines this. Thus, for initiation of an action potential, an extremely greater stimulus compared to normal stimulus is essential for membrane depolarization.

In the heart, low potassium levels make the myocytes hypo-polarized or hyper excitable. Thus, arrhythmia occurs as a result of the atrium’s lowered membrane potential due to recovery from inactivation of the Na channel, which may trigger an action potential. In addition to this, reduced potassium in the extracellular space inhibits the IKr potassium current activity, and ventricular depolarization is delayed, which thereby promotes reentrant arrhythmias.

Hypokalemia Causes

Gastrointestinal/integument Potassium loss:

  • Chronic kidney failure
  • Diarrhea
  • Vomiting
  • Excessive sweating
  • Prescribed diuretic use (water /fluid pills) : most common cause
  • Excessive use of laxatives
  • Diabetic ketoacidosis
  • Primary aldosteronism
  • Pancreatic fistulae
  • Post ileostomy
  • Villous adenoma: it is a colon polyp, where the colon leaks potassium.

Inadequate potassium intake (rare cause)

  • Low potassium diet
  • Starvation (anorexia, bulimia)

Urinary loss

1. Diuretics

  • Thiazide diuretics (Hydrochlorothiazide)
  • Loop diuretics (furosemide)

2. Antibiotics (penicillin, carbenicillin, nafcillin, amphotericin B, gentamicin, foscarnet)
3. Antifungals (amphotericin B)
4. Cancer drug (ciplatin)
5. Diabetic ketoacidosis (here polyuria occurs)
6. Magnesium deficiency (as magnesium is necessary for potassium to be processed)
7. Alkalosis : This causes low potassium level by 2 mechanisms.

  1. Alkalosis causes shifting of potassium from interstitial fluids and plasma into cells, due to Na+-H+ exchange stimulation and the resultant Na+/K+-ATPase activation.
  2. Acute increase of HCO3- concentration in the plasma, caused due to vomiting. This increase is beyond the capacity of reabsorption of the ion by the renal tubule. Thus, potassium excretes as bicarbonate’s cation partner.

Diseases causing high aldosterone levels

These diseases cause excessive potassium loss through urine along with hypertension.

  • Renal artery stenosis
  • Non-malignant adrenal gland tumors (Conn’s syndrome/primary hyperaldosteronism)
  • Cushing’s syndrome
  • Apparent mineralocorticoid excess syndrome : This can be congenital or due to glycyrrhizin consumption, which is found in licorice extract, candies, chewing tobacco, herbal supplements, etc.
  • Bartter syndrome/Gitelman syndrome : This is a rare hereditary non-functioning of renal salt transporters, where the blood pressure may be low. Potassium loss occurs similar to diuretic mechanism.

Distribution away from Extracellular fluid

  • Insulin, epinephrine, and few other beta agonists like salbutamol/salmeterol), and Xanthines like Theophylline
  • Hypokalemic periodic paralysis : This makes the potassium to shift from the ECF to the muscle cells.

Others

  • Thyrotoxic periodic paralysis
  • Cola consumption: this is due to the increased cola intake (4-10L/day), the caffeine’s diuretic effect, and resultant diarrhea. Chronic consumption of such carbonated beverages offset acidosis.

Pseudohypokalemia

  • When blood is drawn, metabolically active cells take excess potassium from the blood and hence, temporary hypokalemia occurs. This is mainly due to the laboratory artifact, which occurs as a result of blood being in warm environment for many hours prior to processing.

Hypokalemia Symptoms

Moderate hypokalemia

  • Weakness, tiredness, or even cramping sensation in arm or leg muscles, which may cause inability to move upper limbs and lower limbs due to weakness (similar to paralysis). This occurs in moderate hypokalemia.
  • Myalgia (moderate hypokalemia)
  • Tingling or numbness
  • Abdominal cramping and bloating
  • Nausea or vomiting
  • Diarrhea
  • Passing large quantity of urine or frequent excess thirst
  • Constipation (due to disturbed muscle function)
  • Fatigue
  • Hypertension
  • Depression, psychosis, confusion, delirium, or hallucinations.

Severe hypokalemia

  • Hyporeflexia or decreased reflexes (severe hypokalemia)
  • Muscle damage (rhabdomyolysis)
  • Palpitations (feeling your irregular heart beat)
  • Respiratory depression
  • Cardiac arrhythmias

Hypokalemia Diagnosis

  • Blood tests
  • Basic/comprehensive metabolic panel
  • Aldosterone test
  • BUN (Blood Urea Nitrogen) & Creatinine (for assessing kidney function)
  • Calcium, magnesium, glucose, phosphorus, thyroxine
  • Digoxin level (to rule out cardiac arrhythmias)
  • Arterial blood gas

Electrocardiogram (ECG or EKG) :

  • A ‘U’ wave: This is due to prolonged ventricular Purkinje fiber repolarization. Hence, prolonged QT interval is seen.
  • Inverted or flattened T waves
  • Wide PR interval
  • ST depression

Hypokalemia Treatment

Mild hypokalemia

  • Oral potassium chloride supplements(during acute stage, avoid sustained release formulations)
  • Diet rich in potassium

Severe hypokalemia

  • Intravenous potassium supplementation: Usually, saline solution with 20-40 mEq of KCl/Liter over 3 to 4 hours is given. Faster IV potassium at the rate of 20-25 mEq/hr. can cause ventricular tachycardia that necessitates intensive monitoring. Hence, the safe dose is 10 mEq/hr.
  • Taking magnesium along with potassium is essential, as it helps in bringing the potassium level to a normal range.
  • To prevent vein damage and burning sensation experienced during IV infusion, prefer central line for replacing the lost potassium intravenously. The burning sensation can also be decreased by dilution of potassium in greater amounts of IV fluid, or by mixing 1% lidocaine (3 ml) to every 10 meq KCl /50 ml IV fluid. However, adding lidocaine may pose serious medical errors.

Difficult/resistive cases:

  • Diuretics (water pills): These increase the serum potassium levels, as the kidneys are allowed to retain potassium, when extra fluid is urinated. For instance, Spirinolactone, amiloride and triamterene
  • Drugs to decrease the hormone level responsible for potassium loss, as in thyrotoxic periodic paralysis.

Hypokalemia Complications

  • Paralysis (in severe cases)
  • Cardiac arrhythmias
  • Hypokalemic nephropathy

Association of hypokalemia and hypertension

The common causes include:-

  • Diuretic use
  • Renal vascular disease
  • Cushing’s syndrome
  • Pheochromocytoma
  • Primary aldosteronism
  • Malignant hypertension

Treatment

  • Initially treat hypokalemia by supplementing the lost potassium.
  • Next, take a random PAC:PRA, to conclude that the patient is not taking any aldosterone-receptor antagonist. Ratio of greater than 30 with PAC (>15NG/dL) is an indication of primary aldosteronism that is causing the resultant hypertension.
  • To rule out renal vascular disease, a CT angiography or MRI is essential, is the activity of plasma renin is high.
  • If clinical suspicion of Cushing’s syndrome, pheochromocytoma, etc., is suspected, then an urinary fractionated metanephrines (24 hour) or dexamethasone-suppression test (low dose), or urinary free cortisol(24 hour) is given.
  • Endocrinology and Nephrology consultation is recommended for evaluating and interpreting the results obtained.

Hypokalemia Prognosis

Regular intake of potassium supplements may correct hypokalemia. However, in untreated hypokalemia, severe potassium level drop is seen that can cause life-threatening arrhythmia.

Things to do when diagnosed as hypokalemia:

1. Follow your doctor’s instructions regarding correction of hypokalemia. He may recommend you to take potassium supplements in the form of pill or IV.
2. Cardiac patients having chronic hypokalemia are advised to consume potassium rich diet.
3. Potassium rich diet includes:

  • Oranges and orange juice
  • Potatoes
  • Green leafy vegetables (collard and kale, spinach)

4. Avoid alcohol and caffeine, as these can cause disturbances of electrolytes.
5. Follow all the recommendations of your physician for blood work, laboratory tests and follow-up.

When to Call Your Doctor in hypokalemia?

  • Nausea interfering with your eating ability, and is unrelieved by the prescribed medication.
  • Vomiting (more than 4-5 times every 24 hour period).
  • Severe diarrhea (more than 5 stools per day)
  • Palpitations (feeling your rapid heartbeats).
  • Weak or absent heartbeat.
  • Chest pain or discomfort, breathing difficulty (needs immediate evaluation)
  • Feeling your rapid heartbeats (palpitations)
  • Loss of consciousness.
  • Muscle weakness, and non-improving poor appetite.

Hypokalemia Prevention

1. Follow the prescribed schedule always.

2. Never start or stop any medicines without your doctor’s permission.

3. Disclose details of any medicines, supplements or vitamins taken or currently taking

4. Eat foods rich in potassium, which includes:

  • Sweet potatoes/baked potatoes
  • Oranges and juice
  • Tomato paste, juice and sauce
  • Beans, lentils, and soybeans
  • Mushrooms, beets and peas
  • Yogurt and milk (low-fat)
  • Tuna, rockfish, halibut and cod
  • Bananas, apricots, prunes, peaches, grapefruit and cantaloupe
  • Spinach

References

http://en.wikipedia.org/wiki/Hypokalemia

http://www.mayoclinic.com/health/low-potassium/MY00760

http://www.nlm.nih.gov/medlineplus/ency/article/000479.htm

http://www.medicinenet.com/low_potassium_hypokalemia/article.htm

http://www.emedicinehealth.com/low_potassium/article_em.htm

http://www.hypokalemia.net/

http://www.chemocare.com/managing/hypokalemia-low-potassium.asp

http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/748/viewAbstract

http://www.myoptumhealth.com/portal/Information/item/Hypokalemia%3A+When+Your+Potassium+Is+Too?archiveChannel=Home%2FArticle&clicked=true

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