Weakness in a Young Woman

April 15, 2007

A 24-year-old woman presents to the emergency department (ED) withgeneralized weakness, headache, and muscle cramping that have progressivelyworsened over the past week. Recently, she has also had nauseaand vomiting. She denies chest pain, palpitations, dyspnea, cough, fever,chills, diarrhea, and urinary symptoms. She has a history of type 1 renaltubular acidosis.

A 24-year-old woman presents to the emergency department (ED) with generalized weakness, headache, and muscle cramping that have progressively worsened over the past week. Recently, she has also had nausea and vomiting. She denies chest pain, palpitations, dyspnea, cough, fever, chills, diarrhea, and urinary symptoms. She has a history of type 1 renal tubular acidosis.

Temperature is 36.2°C (97.1°F); heart rate, 71 beats per minute; respiration rate, 18 breaths per minute; and blood pressure, 98/68 mm Hg. Chest is clear, and results of a cardiac examination are normal. Sensation and motor strength are intact; her gait is steady but slow. Because the patient's complaints are nonspecific, an ECG is obtained (shown here).

Which of the following diagnoses is best supported by the ECG and clinical findings?

A.

Digitalis effect.

B.

Hypokalemia.

C.

Hypothyroidism.

D.

Hypercalcemia.

E.

Romano-Ward syndrome.

(Continued on next page.)

Figure 1

CORRECT ANSWER: BWHAT THE ECG SHOWS
The ECG shows sinus rhythm with prominent U-wave deflections following the T waves (Figure 1). This finding is readily apparent in the precordial leads and is most consistent with a diagnosis of hypokalemia (B). Other ECG findings associated with low serum potassium levels include flattened or inverted T waves, ST-segment depression and, in severe cases, ventricular dysrhythmias (Table).

The computer analysis of the ECG reported a QTc interval prolonged to a remarkable 0.627 second. This might suggest classic prolonged QT syndrome, possibly of congenital origin (eg, Romano-Ward syndrome [E]) or resulting from a metabolic disease, such as hypothyroidism (C). However, because the T wave has a diminished amplitude, the U-wave deflection in this patient's ECG overlaps both the preceding T wave and the P wave of the next cardiac cycle. This gives the appearance of a long QT interval, when the interval is, in fact, a QTU interval.

 Table - ECG findings associated with hypokalemia
ST-segment depression 

 

Digitalis (A) shortens the QTc interval, as does hypercalcemia (D) (calcium levels are in inverse proportion to the QT interval).

THE U WAVE
The U wave itself is a small rounded deflection with an ascent that is shorter than its descent, although it can have a symmetric appearance. A U wave on the ECG can be a normal finding. U waves are normally no more than one quarter the height of the T waves they follow.1,2 At normal heart rates, the duration from the apex of the T wave to the apex of the U wave is 0.10 second. The normal U wave is directed leftward and anteriorly, with an axis of approximately +60 degrees (similar to that of the T wave). U waves are usually most prominent in leads II and V2 through V4, and least prominent in leads I and aVL; they typically appear as negative deflections in leads aVR, aVF, and III. The U wave is often inconspicuous in appearance in healthy persons and can be mistaken for part of the T wave or a prolonged QT interval.

The exact mechanism that produces the U wave is unknown. Several hypotheses have been proposed to explain this last deflection of ventricular repolarization; these include:

  • Delayed repolarization of the Purkinje fibers.
  • Afterpotentials generated by mechanico-electrical coupling during ventricular relaxation.
  • Longer duration of the action potential of conducting myocytes.
  • Repolarization of the papillary muscle cells or other portion of the ventricular myocardium.3

U waves of increased amplitude can be seen with exercise, pheochromocytoma, and certain medications, including digoxin and other inotropic agents, amiodarone, and quinidine. Larger U waves may also be seen in the cardiac cycle that immediately follows a long pause, such as occurs with extrasystole beats. Similarly, larger U waves can be seen with significant bradycardia. Young athletes may have large U waves with amplitudes of up to 2 mm. Prominent U waves with amplitudes greater than 1.5 mm can occur in patients who have experienced an acute CNS event, such as a cerebrovascular infarct or isch- emia. In these patients, however, the U waves are often obscured by a rapid heart rate and increased T-wave amplitude.

U WAVES IN HYPOKALEMIA
Although they can have a variety of causes, pathologic U waves are most commonly associated with hypokalemia. Low serum potassium levels affect the transmembrane gradient across the cardiac cells, with the following results:

  • Elevation in the resting membrane potential.
  • Increase in the duration of the action potential and refractory period.
  • Prolongation of phase 3 repolarization of the cardiac cycle.

Progressive declines in the serum potassium level have a pronounced effect on the ECG. The earliest sign of hypokalemia is often a decrease in T-wave amplitude. As hypokalemia becomes more severe, ST-segment depression and T-wave inversion may be seen. With significant decreases in the serum potassium level, prominent U waves appear, particularly in the mid-precordial leads. Prominent U waves are considered a classic ECG finding associated with hypokalemia.4

With severe hypokalemia, giant U waves can occur; often, these mask the smaller preceding T waves. In addition, the PR interval and the QT interval-or more correctly, the QTU interval-can be prolonged. As a result, patients with severe hypokalemia are at risk for life-threatening dysrhythmias, including ventricular tachycardia, torsade de pointes, and ventricular fibrillation.5

Treatment of severe hypokalemia focuses primarily on aggressive parenteral and oral potassium repletion. In addition, identification of the cause of the hypokalemia, such as inadequate intake or excessive renal or GI losses, is essential.

Figure 2

Figure 3

OUTCOME OF THIS CASE
This patient had a history of chronic episodic hypokalemia as a result of her renal tubular acidosis. She had run out of her potassium supplement 4 days before her presentation. In the ED, her serum potassium level was 1.9 mEq/L. She was admitted to the hospital for intravenous and oral potassium supplementation.

On the first day of admission, a second ECG was obtained (Figure 2), which showed diminishment of the giant U waves. However, U waves were still present, most notably in leads V4 and V5. The patient's serum potassium level at this time was 2.2 mEq/L. She continued to receive aggressive repletion and electrolyte correction, and by day 4 of her hospitalization her condition had improved. An ECG obtained before discharge showed resolution of the changes associated with hypokalemia (Figure 3). The patient went home in good condition, with a potassium level of 3.6 mEq/L.

References:

REFERENCES:1.Yan GX, Lankipalli RS, Burke JF, et al. Ventricular repolarization components in the electrocardiogram. J Amer Coll Cardiol. 2003;42:401-409.
2.Surawicz B. U waves: facts, hypotheses, misconceptions, and misnomers. J Cardiovasc Electrophysiol. 1998;9:1117-1128.
3.Surawicz B. Electrolytes and the electrocardiogram. Postgrad Med. 1974;55:123-129.
4.Diercks DB, Shumaik GM, Harrigan RA, et al. Electrocardiographic manifestations: electrolyte abnormalities. J Emerg Med. 2004;27:153-160.
5.Helfant RH. Hypokalemia and arrhythmias. Am J Med. 1986;80:13-22.