Hypokalemia

Hypokalemia is a serum potassium concentration of less than 3.5 mEq/L caused by a deficiency of total body potassium or abnormal movement of potassium into cells. The most common causes are increased renal or gastrointestinal losses. Clinical manifestations include muscle weakness, polyuria; myocardial hyperexcitability may develop with severe hypokalemia.

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Causes hypokalemia

Hypokalemia is conventionally divided into so-called pseudohypokalemia, i.e. occurring without loss of potassium, and hypokalemia with loss of potassium.

Pseudohypokalemia develops with inadequate intake of potassium into the body (depletion syndrome) or potassium shift from the extracellular space to the intracellular space. Hormones (insulin and adrenaline) promote the electrolyte shift into the intracellular space. Hypokalemia is caused by an increase in insulin levels caused by hyperglycemia or the introduction of exogenous insulin. Endogenous release of catecholamines during stress or the use of beta ₂ -adrenomimetics are also accompanied by a decrease in the concentration of potassium in the blood serum. Redistribution of potassium with its shift into cells occurs with hereditary hypokalemic periodic paralysis, thyrotoxicosis (thyrotoxic hypokalemic paralysis).

In clinical practice, hypokalemia caused by potassium loss is more common. Potassium losses are divided into extrarenal (usually through the gastrointestinal tract) and renal. The distinction between these conditions is based on determining the concentration of chlorides in the urine. If chlorides are excreted in the urine <15 mmol/l, there is a high probability that electrolytes are lost through the gastrointestinal tract.

The main causes of extrarenal potassium losses are: persistent vomiting (neurogenic anorexia, gastrointestinal diseases), diarrhea (gastrointestinal diseases, excessive use of laxatives). In these situations, hypokalemia is usually accompanied by the development of metabolic alkalosis, which occurs due to the depletion of chloride reserves in the body, which adaptively leads to intensive reabsorption of chlorides in the kidneys and increased renal excretion of potassium.

Renal potassium loss is diagnosed when patients with hypokalemia are found to have excessive excretion of potassium and chlorides in the urine that is “not appropriate to the condition” (kaliuria over 20 mmol/day, chloride excretion over 60 mmol/l). Diseases that occur with similar electrolyte disturbances differ in the level of arterial pressure. In this regard, the classification of causes of renal potassium loss is divided into 2 groups of pathological conditions: normotensive (group A) and hypertensive (group B) conditions. The latter group is further subdivided depending on the level of circulating aldosterone and plasma renin.

Normotensive conditions (group A):

• abuse of diuretics (loop, thiazide, acetazolamide);
• Bartter's syndrome;
• Gitelman syndrome;
• immune potassium penic interstitial nephritis;
• renal tubular acidosis type I and II.

Hypertensive conditions (group B):

• with high levels of aldosterone and renin (primary aldosteronism due to adenoma and adrenal hyperplasia);
• with high aldosterone and low renin levels (malignant hypertension, renovascular hypertension, renin-secreting tumor);
• with low levels of aldosterone and renin (use of mineralocorticoids, glycyrrhizic acid, carbenonesolone);
• with normal levels of aldosterone and renin (Itsenko-Cushing syndrome).

Among the renal potassium losses of group A, the most common are diuretic abuse and Gitelman syndrome.

In clinical practice, hypokalemia often develops due to abuse of diuretics or laxatives. As a rule, this situation is typical for young women who strictly monitor their figure due to their character or profession. The main clinical and laboratory manifestations are weakness, hypokalemia and hypochloremia, metabolic alkalosis, high concentration of potassium and chlorine in urine (chlorine concentration over 60 mmol/l), normal blood pressure values. To diagnose this condition, it is necessary to carefully collect the patient's anamnesis and confirm the presence of diuretics in several urine samples.

Less frequently diagnosed Bartter syndrome is indistinguishable from diuretic abuse in its clinical and laboratory manifestations. However, Bartter syndrome is usually a pathology of early childhood. It is most often detected in children with intrauterine developmental disorders (intrauterine growth retardation, polyhydramnios), and often in premature births. The main clinical signs are hypokalemia, polyuria with potassium depletion, low blood pressure, secondary hyperaldosteronism, and metabolic alkalosis. The content of Mg2 ⁺ in the blood and excretion of Ca2 ⁺ in the urine are within normal values. In Bartter syndrome, hyperplasia of the juxtamedullary apparatus is detected, which is accompanied by a sharp increase in the production of renin and aldosterone. The severe electrolyte disturbances in this syndrome are caused by gene defects associated with a mutation in the TALH gene, which is responsible for chloride reabsorption in the distal straight tubule.

Gitelman syndrome, described in the late 1960s, is currently considered the most common cause of hypokalemic kidney damage. More than 50% of all cases of hypokalemia are associated with this syndrome. The disease develops in adults and is manifested by moderate hypokalemia (serum potassium is within 2.4-3.2 mmol / l), which does not reduce the quality of life, does not cause heart rhythm disturbances and muscle weakness. Examination often reveals a decrease in the concentration of Mg ²⁺ in the blood, borderline hypochloremia, mild metabolic alkalosis and secondary hyperaldosteronism. The kidney function of these patients remains intact for a long time. Increased excretion of chlorides and hypocalciuria are noticeable during urine examination. A decrease in the level of magnesium in the blood serum and hypocalciuria are considered diagnostically significant signs. The cause of Gitelman syndrome is associated with a mutation of the thiazide-sensitive Na ⁺ -Q~ cotransporter in the distal tubules of the nephron, which makes it possible to diagnose this condition using genotyping. Potassium-rich foods and potassium supplements are used to correct hypokalemia. The prognosis for patients with Gitelman syndrome is favorable.

Rare causes of hypokalemia are immune potassiumpenic interstitial nephritis. This disease also has hypokalemia (moderate to severe), hyperkaliumuria, metabolic alkalosis, and moderate hyperaldosteronism. The concentration of calcium and phosphorus in the blood serum is usually within normal values. A distinctive feature of the disease is the presence of concomitant autoimmune manifestations (iridocyclitis, immune arthritis, or detection of high titer rheumatoid factor or autoantibodies). Lymphocytic infiltrates in the interstitium are often found in kidney biopsies. The cause of electrolyte disturbances in this situation is associated with damage to ion transporters, but, in contrast to Bartter and Gitelman syndromes, it is not of gene-determined origin, but of immune origin.

A common cause of hypokalemia, along with the conditions presented above, is renal tubular acidosis of the distal (I) and proximal (II) type. The predominant clinical manifestations of the disease are severe hypokalemia and metabolic acidosis. A similar clinical picture is also caused by long-term use of carbonic anhydrase inhibitors (acetazolamide).

In patients with potassium loss in hypertensive conditions (group B), the main cause of hypokalemia is excessive production of mineralocorticoid hormones, primarily aldosterone. These patients usually develop hypochloremic metabolic alkalosis. The combination of high aldosterone concentrations and low plasma renin activity is observed in primary aldosteronism, which develops in adenoma, hyperplasia, or carcinoma of the zona glomerulosa of the adrenal cortex. Hyperaldosteronism with high plasma renin levels is usually detected in malignant hypertension, renovascular hypertension, and renin-secreting tumors. Hypokalemia against the background of hypertension with normal plasma aldosterone and renin levels develops in Itsenko-Cushing syndrome.

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Symptoms hypokalemia

Mild hypokalemia (plasma potassium level 3-3.5 mEq/L) rarely causes symptoms. When plasma potassium level is less than 3 mEq/L, muscle weakness usually develops, which may lead to paralysis and respiratory arrest. Other muscle abnormalities include cramps, fasciculations, paralytic ileus, hypoventilation, hypotension, tetany, and rhabdomyolysis. Persistent hypokalemia may impair the renal concentrating ability, causing polyuria with secondary polydipsia.

The cardiac effects of hypokalemia are minimal until plasma potassium is < 3 mEq/L. Hypokalemia causes ST-segment depression, T-wave depression, and U-wave elevation. With significant hypokalemia, the T-wave progressively decreases and the U-wave increases. Sometimes a flat or upright T-wave merges with an upright U-wave, which may be mistaken for a prolonged QT. Hypokalemia may cause premature atrial and ventricular contractions, ventricular and atrial tachyarrhythmias, and second- or third-degree atrioventricular blocks. Such arrhythmias increase with more severe hypokalemia; ventricular fibrillation may result. Patients with underlying heart disease and/or taking digoxin are at high risk for cardiac conduction abnormalities even with mild hypokalemia.

Symptoms of hypokalemia are as follows:

• skeletal muscle damage (muscle weakness, fatigue, flaccid paralysis, rhabdomyolysis);
• smooth muscle damage (decreased motility of the stomach and small intestine);
• damage to the heart muscle (decrease in the T wave, prolongation of the QT interval, appearance of a pronounced U wave, widening of the QRS complex and development of atrioventricular block);
• damage to peripheral nerves (paresthesia and rigidity of the limbs);
• kidney damage with the development of polyuria, nocturia (due to impaired concentrating ability of the kidneys) and primary polydipsia.

Long-term depletion of potassium stores can cause interstitial nephritis and the development of renal failure, and in some cases, the formation of cysts in the kidneys.

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Diagnostics hypokalemia

Hypokalemia is diagnosed when the plasma K level is less than 3.5 mEq/L. If the cause is not obvious from the history (eg, medications), further evaluation is necessary. After ruling out acidosis and other causes of intracellular K shift, 24-hour urinary K levels are measured. In hypokalemia, K secretion is usually less than 15 mEq/L. Extrarenal K loss or decreased dietary K intake is seen in cases of chronic unexplained hypokalemia, when renal K secretion is < 15 mEq/L. Secretion > 15 mEq/L suggests a renal cause for K loss.

Unexplained hypokalemia with increased renal K secretion and hypertension suggests an aldosterone-secreting tumor or Liddle's syndrome. Hypokalemia with increased renal K loss and normal BP suggests Bartter's syndrome, but hypomagnesemia, occult vomiting, and diuretic abuse are also possible.

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Treatment hypokalemia

Symptoms of hypokalemia, confirmed by the detection of low serum electrolyte levels, require immediate correction of the electrolyte balance, since a decrease in serum potassium by 1 mmol/l (in the concentration range of 2-4 mmol/l) corresponds to a decrease in its total reserves in the body by 10%.

There are various oral K preparations. Because they cause gastrointestinal irritation and occasional bleeding, they are usually given in divided doses. Liquid KCI, when given orally, increases K levels within 1-2 hours but is poorly tolerated at doses greater than 25-50 mEq because of its bitter taste. Film-coated KCI preparations are safe and better tolerated. GI bleeding is less common with microencapsulated preparations. Several preparations are available that contain 8-10 mEq per capsule.

In severe hypokalemia unresponsive to oral therapy or in hospitalized patients in the active phase of the disease, K replacement should be performed parenterally. Since K solutions can have an irritating effect on peripheral veins, the concentration should not exceed 40 mEq/L. The rate of correction of hypokalemia is limited by the period of K movement into cells; normally, the rate of administration should not exceed 10 mEq/hour.

In hypokalemia-induced arrhythmias, intravenous KCI should be given more rapidly, usually via the central vein or using several peripheral veins simultaneously. KCI 40 mEq/h may be given, but only with ECG monitoring and hourly plasma K levels. Glucose solutions are undesirable because an increase in plasma insulin levels may lead to a transient worsening of hypokalemia.

In K deficiency with high plasma K concentrations, as seen in diabetic ketoacidosis, intravenous K administration is delayed until plasma K levels begin to decline. Even in cases of severe K deficiency, it is usually not necessary to administer more than 100-120 mEq K in 24 hours unless K loss continues. In cases of hypokalemia and hypomagnesemia, correction of K and Mg deficits is necessary to avoid continued renal K loss.

Patients taking diuretics do not need constant intake of K. However, when taking diuretics, it is necessary to monitor the plasma K level, especially in patients with decreased left ventricular function, taking digoxin, in the presence of diabetes mellitus, in patients with asthma receiving beta-agonists. Triamterene at a dose of 100 mg orally once a day or spironolactone at a dose of 25 mg orally do not increase the excretion of K and can be taken by patients who develop hypokalemia, but who cannot refuse to take diuretics. If hypokalemia develops, K replacement is necessary. If the K level is less than 3 mEq / L, oral administration of KCI is necessary. Since a decrease in the plasma K level by 1 mEq / L correlates with a total K deficit in the body of 200-400 mEq, an intake of 20-80 mEq / day is necessary for several days to correct the deficit. When resuming feeding after a prolonged fast, it may be necessary to take K supplements for several weeks.

Hypokalemia against the background of diuretic intake and Gitelman syndrome is rarely pronounced (from 3 to 3.5 mmol/l), and in patients not treated with digitalis, the above changes rarely lead to severe complications. Due to the concomitant loss of potassium in the urine and depletion of magnesium reserves, an electrolyte involved in the functioning of many enzymes that occur with the participation of adenosine triphosphate (ATP) and, accordingly, participate in the regulation of the cardiovascular and nervous systems, even a mild degree of hypokalemia should be corrected. In these situations, the physician's tactics should be aimed at discontinuing potassium-sparing diuretics (if possible given the patient's condition) or additionally prescribing potassium-sparing diuretics in combination with the administration of potassium preparations. A low sodium diet (70-80 mmol/day) also helps to reduce the severity of hypokalemia.

In cases of more severe and poorly corrected hypokalemia, potassium homeostasis is normalized by administering large doses of potassium chloride orally in combination with potassium-sparing diuretics (amiloride, triamterene, or spironolactone).

Treatment of hypokalemia in metabolic alkalosis involves the use of potassium chloride, and in the treatment of renal tubular acidosis - potassium bicarbonate. Intravenous administration of these drugs is justified in the case of severe hypokalemia (serum potassium concentration less than 2.5 mmol/l and the presence of clinical signs of potassium deficiency - changes in the electrocardiogram, muscle weakness). The named potassium preparations are administered intravenously in doses that provide potassium intake at a concentration of 0.7 mmol/kg over 1-2 hours.

In case of severe hypokalemia (serum potassium below 2.0 mmol/l) or development of arrhythmia, the dose of administered potassium is increased to 80-100 mmol/l. It should be remembered that the introduction of potassium into a peripheral vein at a dose exceeding 60 mmol/l, even at a low rate of administration (5-10 mmol/h), is extremely painful. If rapid intravenous administration of potassium is necessary, the femoral vein can be used. In the development of urgent conditions, potassium solutions are administered at a rate exceeding the calculated rate of potassium loss (from 20 to 60 mmol/h). The administered potassium is initially distributed in the extracellular fluid and then enters the cell. Intensive treatment of hypokalemia is stopped when the degree of hypokalemia no longer poses a threat to the patient's life. This is usually achieved by administering about 15 mmol of potassium in 15 minutes. Subsequently, the potassium deficiency is replenished more slowly under constant monitoring of the electrocardiogram and its level in the blood serum.