Chapter 195:  Serum Potassium

Hypokalemia

Serum potassium concentration does not always reflect total body potassium; therefore, hypokalemia could coexist with both normal or low total body potassium (see Table 195.3).

Hypokalemia with normal total body potassium, by definition, is due to a shift of potassium into the cell. This shift could occur in alkalemia, states of high endogenous or exogenous insulin or catecholamines, and, in very rare situations, for unknown reasons (hypokalemic periodic paralysis). In clinical practice, alkalemia is the most common cause of hypokalemia. Table 195.2 indicates the extent of expected changes in serum potassium with alkalemia of either respiratory or metabolic origin. The figure of 0.25 mEq/L per 0.1 U increase in pH could be used to correct the measured serum potassium.

Hypokalemia without intracellular shift of potassium is seen only when there is marked potassium deficiency. As an approximation, a 1.0 mEq/L decrease in serum potassium is associated with a deficit of 200 to 300 mEq, while a 2.0 mEq/L decrease is associated with a 500 to 600 mEq deficit in total body potassium. It should be noted that any judgment regarding the state of total body potassium is, at best, a gross approximation, and one should utilize all historical, physical, and laboratory information available to make this approximation more accurate. As Table 195.3 indicates, hypokalemia associated with a low total body potassium is either due to poor dietary intake or increased potassium loss from the body. Poor intake is an uncommon cause, for most foods contain some potassium. Nevertheless, patients with extremely poor dietary intake (most commonly alcoholics) and patients on severe weight-reduction programs are in danger of developing severe potassium deficiency. Hypokalemia due to an increase in potassium loss is most commonly secondary to gastrointestinal disorders. Although the potassium content of gastrointestinal fluids is quite low (Table 195.4), the resultant dehydration stimulates aldosterone production, which increases urinary potassium significantly. The renal potassium wasting continues as long as dehydration persists. If gastrointestinal fluid loss is from the stomach, hypokalemia is partly due to intracellular shift of potassium secondary to alkalemia and partly due to increased renal potassium loss due to high aldosterone level. Sweat contains only a small amount of potassium, and excess sweating is rarely the cause of significant hypokalemia.

Renal potassium loss is most commonly associated with a high aldosterone level (either as a primary or secondary event). The most common cause of renal potassium wastage is the use of diuretics that induce kaliuresis through several mechanisms (including increase in aldosterone level, increase in urine volume, increase in the delivery of sodium to the exchange sites, hypochloremia, and metabolic alkalosis). Less commonly, renal potassium wasting results from a primary increase in circulating mineralocorticoids, such as occurs in Cushing's syndrome or primary hyperaldosteronism.

As noted, urinary potassium excretion tends to be elevated in the gastrointestinal as well as the renal causes of hypokalemia. However, the urine potassium is usually below 20 mEq/L in the former and above 20 mEq/L in the latter. The most critical data to differentiate these two large groups are historical (e.g., history of vomiting, diarrhea, or diuretic use) and physical data (blood pressure, pulse, and other volume parameters). More sophisticated laboratory studies are often needed to reach a specific diagnosis in either category.

Hyperkalemia

Serum potassium above 5.5 mEq/L should be worked up rapidly and treated appropriately. Serum potassium above 6.5 mEq/L is associated with significant morbidity and mortality and should be handled as an emergency.

Table 195.5 categorizes hyperkalemia into three groups: pseudohyperkalemia, hyperkalemia with normal total body potassium, and hyperkalemia with high total body potassium.

Pseudohyperkalemia signifies an in vitro phenomenon (i.e., the in vivo serum potassium is normal). This is caused by the release of potassium from cellular components of blood during the process of clotting and, less commonly, by the release of potassium from ischemic muscle cells due to tight tourniquet or hand/arm exercise during the blood-drawing process. If the latter is suspected, blood should be drawn in a proper manner again and serum potassium repeated. If the former is suspected, the platelet and white cell counts should be checked, and serum should be inspected for significant hemolysis. Hyperkalemia occurs when there is thrombocytosis (platelet count greater than 600,000), leukocytosis (WBC greater than 200,000) or significant hemolysis (serum hemoglobin greater than 1.5 g/dl). If thrombocytosis or severe leukocytosis is present, then plasma potassium should be measured. If hemolysis is present, blood drawing should be carefully repeated.

Hyperkalemia with normal total body potassium is caused by the shift of potassium out of the cell and is commonly seen in acidemia, sudden increase in plasma osmolality, massive tissue breakdown and, in very rare circumstances, adrenergic blockade and hyperkalemic periodic paralysis (Table 195.5). Acidemia is by far the most important cause of hyperkalemia. As Table 195.2 shows, mineral acidosis (e.g., renal failure acidosis) is associated with the greatest shift (1.0 mEq/L for each 0.1 U decrease in pH) of potassium, whereas organic acidosis (e.g., lactic acidosis) is associated with little or no change. Respiratory acidosis results in a modest shift (0.2 mEq/L for each 0.1 pH change). These figures, while approximate, can be used to correct the measured serum potassium. Beta blockade can result in significant hyperkalemia during and immediately after exercise. This is because the potassium initially released from the muscle cells is normally taken up by these cells through the stimulation of beta-2 receptors by catecholamines. A sudden rise in osmolality can result in a modest increase in serum potassium (0.3 to 0.5 mEq/L); this rise, however, can be much greater in diabetic patients, who lack normal insulin and aldosterone responses to hyperkalemia.

Hyperkalemia with increase in total body potassium is almost always caused by a decrease in renal excretion of potassium and is rarely the result of an increase in intake alone. Patients with normal kidney function can adapt to increase in potassium intake unless the potassium is given rapidly (e.g., intravenous infusion) or is given to a patient with a renal defect in potassium excretion.

A decrease in renal potassium excretion is either primary renal in origin or caused by a defect in the renin-angiotensin-aldosterone axis. Although potassium excretion is primarily a secretory phenomenon, marked decreases in glomerular filtration rate (GFR) to below 20 ml/min can be associated with hyperkalemia. In patients with relatively normal GFR, hyperkalemia is usually due to a defect in the renin-angiotensin-aldosterone axis or to a defect in the renal tubular responsiveness to aldosterone. In these patients, measurement of plasma aldosterone level and, if needed, further evaluation of the renin-angiotensin-aldosterone axis may be required for definitive diagnosis.