Hypokalemia

A cellular shift of potassium from the extracellular to the intracellular compartment may result in hypokalemia. This occurs with metabolic alkalosis, with insulin or beta-agonist administration, with hyperthyroidism, and in the periodic paralysis syndromes. In general, the magnitude of the hypokalemia that accompanies cellular shifts is modest. In healthy volunteers, a single dose of aerosolized albuterol lowers serum potassium by 0.2-0.4 milliequivalents/L (mEq/L), and this effect may persist for several hours.

In delirium tremens, serum potassium may decline by 1 mEq/L due to the effects of high levels of intrinsic beta-agonists (primarily epinephrine and norepinephrine). When patients with delirium tremens present with serum potassium less than 2.5 mEq/L, this is almost always due to the additive effects of other etiologies (such as vomiting, alkalosis associated with volume depletion, and hypomagnesemia).

In distinction to other diseases that cause intracellular shift of potassium, the hypokalemia seen with the periodic paralysis syndromes (hypokalemic periodic paralysis, thyrotoxic periodic paralysis, and Andersen syndrome) may result in very low levels of serum potassium (less than 2.5 mEq/L).

Extra-renal losses of potassium occur with vomiting and diarrhea. The potassium content in diarrhea is much higher than in vomitus (20-50 mEq/l vs. 5-10 mEq/L), but hypokalemia associated with vomiting is usually much more profound than that with diarrhea. This is because vomiting is much more frequently associated with metabolic alkalosis and volume depletion. These two conditions result in inappropriate renal loss of potassium; a more minor effect is the intracellular shift of potassium that accompanies vomiting-associated alkalosis. Rare extrarenal causes of hypokalemia include the chronic poor potassium intake sometimes seen in chronic beer drinkers who also have hyponatremia (beer potomania), excessive sweating, plasmapheresis, and dialysis.

Renal loss etiologies of hypokalemia include diseases of the kidney (renal tubular acidosis, salt losing nephropathies, Bartter syndrome, and Gitelman syndrome); states associated with delivery of non-reabsorbable anions to the distal nephron (such as ketoacids, bicarbonate, toluene, and penicillins); states of excess mineralocorticoids (Conn’s syndrome, Cushing’s syndrome, corticosteroid administration); hypomagnesemia; and certain drugs (diuretics, amphotericin, and platinum).

B. Describe a diagnostic approach/method to the patient with this problem

In over 90% of hospitalized patients, hypokalemia is associated with one of three clinical conditions: diuretic use, vomiting, or diarrhea. Thus for the hospitalist, the cause of hypokalemia does not usually present diagnostic uncertainty. Even though patients often have more than one cause of hypokalemia, potassium supplementation and treatment of the major underlying cause (discontinuing diuretics, treatment of vomiting or diarrhea) corrects the hypokalemia.

A practical approach to the hospitalized patient with hypokalemia is to initiate treatment and defer laboratory investigation of etiology if the patient has vomiting, diarrhea, or used diuretics. In the absence of one of these etiologies, and in the patient in whom treatment does not correct the hypokalemia, then a more detailed laboratory investigation is warranted.

1. Historical information important in the diagnosis of this problem

Historical inquiry of primary importance includes ascertaining an accurate medication list, and determining whether or not the patient has had vomiting and/or diarrhea. Certain historical features may suggest one of the more unusual causes of hypokalemia, such as a history of recent onset hypertension in Conn’s syndrome, a history of renal stones in renal tubular acidosis, or glue-sniffing in toluene poisoning.

Muscle weakness may accompany serum potassium of less than 2.5 mEq/L due to any etiology, but significant muscle weakness is uncommon and suggests the possibility of one of the periodic paralysis syndromes.

In the periodic paralysis syndromes, muscle weakness is typically worse proximally and in lower extremities. With these syndromes, episodes of weakness and hypokalemia are often precipitated by exercise, stress, or high carbohydrate meals. Most, but not all, patients with thyrotoxic periodic paralysis are Asian men who have had symptoms of hyperthyroidism for several months.

Though the periodic paralysis syndromes are rare, they are important to recognize for two reasons. First, these patients often experience hyperkalemia during the recovery phase of their illness as potassium shifts back into the extracellular compartment, and therefore more cautious potassium replacement is warranted. Secondly, preventive therapies are available and may be offered to these patients to prevent or ameliorate subsequent episodes. Thus, patients with hypokalemia and acute muscle weakness should be carefully questioned about the presence of previous episodes of muscle weakness and symptoms of hyperthyroidism (such as weight loss, tremor, and palpitations).

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

Severe hypokalemia (serum potassium less than 2.5 mEq/l) may be accompanied by muscle weakness and ileus, but in general the physical examination is usually not helpful diagnostically in hospitalized patients with hypokalemia. The exception to this is patients with one of the periodic paralysis syndrome. These patients typically have proximal motor weakness and hyporeflexia in the presence of a normal level of consciousness.

Patients with vomiting often have findings of volume depletion (tachycardia, low blood pressure, fall in blood pressure with standing), and these findings would suggest the need for volume repletion in addition to potassium administration. Rare causes of hypokalemia may be accompanied by such physical examination signs such as abdominal striae and centripetal obesity in Cushing’s syndrome.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

As noted above, laboratory investigation into the etiology of hypokalemia may be deferred if the patient has vomiting, diarrhea, or used diuretics. In patients in whom the etiology is less obvious, determination of acid-base status (pH from an arterial blood gas) and an estimate of urine potassium secretion are the first diagnostic steps.

Determining renal potassium excretion is most accurately done with a 24-hour collection. In the presence of hypokalemia, 24-hour potassium loss of more than 30 mEq suggests some component of inappropriate renal loss. Random urine potassium measurements can result in misleading results.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Specific diagnoses are suggested by examining the blood pH and urine potassium secretion (Table II).