Diarrhea, the most common cause of metabolic acidosis in children, causes a loss of

bicarbonate from the body. The amount of bicarbonate lost in the stool depends
on the volume of diarrhea and the bicarbonate concentration of the stool, which tends to
increase with more severe diarrhea. The kidneys attempt to balance the losses
by increasing acid secretion, but metabolic acidosis occurs when this compensation is
inadequate. Diarrhea often causes volume depletion as a result of losses of
sodium and water, potentially exacerbating the acidosis by causing hypoperfusion and a
lactic acidosis. In addition, diarrheal losses of potassium lead to hypokalemia.
Moreover, the volume depletion causes increased production of aldosterone. This
stimulates renal retention of sodium, helping to maintain intravascular volume, but
also leads to increased urinary losses of potassium, exacerbating the hypokalemia.
There are three forms of renal tubular acidosis (RTA): distal (type I), proximal (type II),
and hyperkalemic (type IV) (see Chapter 521 ). In distal RTA, children may have
accompanying hypokalemia, hypercalciuria, nephrolithiasis, and nephrocalcinosis.
Failure to thrive caused by chronic metabolic acidosis is the most common
presenting complaint. There are autosomal dominant and autosomal recessive forms of
distal RTA. The autosomal dominant form is relatively mild; many patients do
not present until adulthood. Autosomal recessively inherited distal RTA is more severe
and is often associated with deafness. Patients with distal RTA cannot acidify
their urine and, thus, have a urine pH > 5.5 despite a metabolic acidosis.
Proximal RTA is rarely present in isolation. In most patients, proximal RTA is part of
Fanconi syndrome, a generalized dysfunction of the proximal tubule. This leads to
glycosuria, aminoaciduria, and excessive urinary losses of phosphate and uric acid. The
presence of a low serum uric acid level, glycosuria, and aminoaciduria is
helpful diagnostically. Chronic hypophosphatemia ultimately leads to rickets in children.
Rickets and/or failure to thrive may be the presenting complaint. The ability to
acidify the urine is intact in proximal RTA; thus, untreated patients have a urine pH <
5.5. However, bicarbonate therapy increases bicarbonate losses in the urine and
the urine pH increases.
In hyperkalemic RTA, renal excretion of acid and potassium is impaired. Hyperkalemic
RTA is due to either an absence of aldosterone or an inability of the kidney to
respond to aldosterone (see Chapter 521 ). In severe aldosterone deficiency, as occurs
with congenital adrenal hyperplasia due to 21a-hydroxylase deficiency, the
hyperkalemia and metabolic acidosis are accompanied by hyponatremia and volume
depletion from renal salt wasting. Incomplete aldosterone deficiency causes less
severe electrolyte disturbances; children may have isolated hyperkalemic RTA,
hyperkalemia without acidosis, or isolated hyponatremia. Patients may have
aldosterone deficiency due to decreased renin production by the kidney; renin normally
stimulates aldosterone synthesis. Children with hyporeninemic
hypoaldosteronism usually have either isolated hyperkalemia or hyperkalemic RTA. The
manifestations of aldosterone resistance depend on the severity of the
resistance. In the autosomal recessive form of pseudohypoaldosteronism type I, which
is due to an absence of the sodium channel that normally responds to
aldosterone, there is often severe salt wasting and hyponatremia. In contrast, the
aldosterone resistance in kidney transplant patients usually produces either isolated
hyperkalemia or hyperkalemic RTA; hyponatremia is unusual. Similarly, the medications
that cause hyperkalemic RTA do not cause hyponatremia.
Pseudohypoaldosteronism type II, an autosomal recessive disorder called Gordon
syndrome, is a unique cause of hyperkalemic RTA because the genetic defect
causes volume expansion and hypertension.