Chapter 046. Sodium and Water (Part 14) pptx

Chapter 046. Sodium and Water (Part 14) Liddle's syndrome is a rare familial (autosomal dominant) disease characterized by hypertension, hypokalemic metabolic alkalosis, renal K + wasting, and suppressed renin and aldosterone secretion. Increased distal delivery of Na + with a nonreabsorbable anion (not Cl – ) enhances K + secretion. Classically, this is seen with proximal (type 2)renal tubular acidosis (RTA) and vomiting, associated with bicarbonaturia. Diabetic ketoacidosis and toluene abuse (glue sniffing) can lead to increased delivery of β-hydroxybutyrate and hippurate, respectively, to the CCD and to renal K + loss. High doses of penicillin derivatives administered to volume-depleted patients may likewise promote renal K + secretion as well as an osmotic diuresis. Classic distal (type 1) RTA is associated with hypokalemia due to increased renal K + loss, the mechanism of which is uncertain. Amphotericin B causes hypokalemia due to increased distal nephron permeability to Na + and K + and to renal K + wasting. Bartter's syndrome is a disorder characterized by hypokalemia, metabolic alkalosis, hyperreninemic hyperaldosteronism secondary to ECF volume contraction, and juxtaglomerular apparatus hyperplasia. Finally, diuretic use and abuse are common causes of K + depletion. Carbonic anhydrase inhibitors, loop diuretics, and thiazides are all kaliuretic. The degree of hypokalemia tends to be greater with long-acting agents and is dose-dependent. Increased renal K + excretion is due primarily to increased distal solute delivery and secondary hyperaldosteronism (due to volume depletion). See also Chap. 278. Clinical Features The clinical manifestations of K + depletion vary greatly between individual patients, and their severity depends on the degree of hypokalemia. Symptoms seldom occur unless the plasma K + concentration is <3 mmol/L. Fatigue, myalgia, and muscular weakness of the lower extremities are common complaints and are due to a lower (more negative) resting membrane potential. More severe hypokalemia may lead to progressive weakness, hypoventilation (due to respiratory muscle involvement), and eventually complete paralysis. Impaired muscle metabolism and the blunted hyperemic response to exercise associated with profound K + depletion increase the risk of rhabdomyolysis. Smooth-muscle function may also be affected and manifest as paralytic ileus. The electrocardiographic changes of hypokalemia (Fig. 221-16) are due to delayed ventricular repolarization and do not correlate well with the plasma K + concentration. Early changes include flattening or inversion of the T wave, a prominent U wave, ST-segment depression, and a prolonged QU interval. Severe K + depletion may result in a prolonged PR interval, decreased voltage and widening of the QRS complex, and an increased risk of ventricular arrhythmias, especially in patients with myocardial ischemia or left ventricular hypertrophy. Hypokalemia may also predispose to digitalis toxicity. Hypokalemia is often associated with acid-base disturbances related to the underlying disorder. In addition, K + depletion results in intracellular acidification and an increase in net acid excretion or new HCO 3 – production. This is a consequence of enhanced proximal HCO 3 – reabsorption, increased renal ammoniagenesis, and increased distal H + secretion. This contributes to the generation of metabolic alkalosis frequently present in hypokalemic patients. NDI (see above) is not uncommonly seen in K + depletion and is manifest as polydipsia and polyuria. Glucose intolerance may also occur with hypokalemia and has been attributed to either impaired insulin secretion or peripheral insulin resistance. Diagnosis (Fig. 46-3) In most cases, the etiology of K + depletion can be determined by a careful history. Diuretic and laxative abuse as well as surreptitious vomiting may be difficult to identify but should be excluded. Rarely, patients with a marked leukocytosis (e.g., acute myeloid leukemia) and normokalemia may have a low measured plasma K + concentration due to white blood cell uptake of K + at room temperature. This pseudohypokalemia can be avoided by storing the blood sample on ice or rapidly separating the plasma (or serum) from the cells. Figure 46-3 . Chapter 046. Sodium and Water (Part 14) Liddle's syndrome is a rare familial (autosomal dominant) disease. tubular acidosis (RTA) and vomiting, associated with bicarbonaturia. Diabetic ketoacidosis and toluene abuse (glue sniffing) can lead to increased delivery of β-hydroxybutyrate and hippurate, respectively,. volume contraction, and juxtaglomerular apparatus hyperplasia. Finally, diuretic use and abuse are common causes of K + depletion. Carbonic anhydrase inhibitors, loop diuretics, and thiazides are