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