Diarrhea 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. Diarrhea often causes volume depletion because of losses of sodium and water, potentially exacerbating the acidosis by causing hypoperfusion (shock) and a lactic acidosis. There are three forms of renal tubular acidosis (RTA):
In distal RTA, children may have accompanying hypokalemia, hypercalciuria, nephrolithiasis, and nephrocalcinosis; rickets is a less common finding. Failure to thrive, resulting from chronic metabolic acidosis, is the most common presenting complaint. Autosomal dominant and autosomal recessive forms of distal RTA exist. The autosomal dominant form is relatively mild. Autosomal recessive distal RTA is more severe and often associated with deafness secondary to a defect in the gene for a H+-ATPase that is present in the kidney and the inner ear. Distal RTA also may be secondary to medications or congenital or acquired renal disease. Patients with distal RTA cannot acidify their urine and have a urine pH greater than 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. Along with renal wasting of bicarbonate, Fanconi syndrome causes glycosuria, aminoaciduria, and excessive urinary losses of phosphate and uric acid.The chronic hypophosphatemia is more clinically significantbecause it ultimately leads to rickets in children. Rickets orfailure to thrive may be the presenting complaint. Fanconisyndrome is rarely an isolated genetic disorder, with pediatriccases usually secondary to an underlying genetic disorder, mostcommonly cystinosis. Medications, such as ifosfamide or valproate, may cause Fanconi syndrome. The ability to acidify theurine is intact in proximal RTA, and untreated patients have aurine pH less than 5.5. However, bicarbonate therapy increasesbicarbonate losses in the urine, and the urine pH increases.
In hyperkalemic RTA, renal excretion of acid and potassium is impaired because of either an absence of aldosterone
Lactic acidosis (shock) Ketoacidosis (diabetic, starvation, or alcoholic) Kidney failure Poisoning (e.g., ethylene glycol, methanol, or salicylates) Inborn errors of metabolism *[HCO3–] is expressed in mEq/L.
or an inability of the kidney to respond to aldosterone. Insevere aldosterone deficiency, as occurs with congenital adrenal hyperplasia secondary to 21α-hydroxylase deficiency, the hyperkalemia and metabolic acidosis are accompanied byhyponatremia and volume depletion from renal salt wasting.Incomplete aldosterone deficiency causes less severe electrolytedisturbances; children may have isolated hyperkalemic RTA,hyperkalemia without acidosis, or isolated hyponatremia.
Lactic acidosis most commonly occurs when inadequate oxygen delivery to the tissues leads to anaerobic metabolism and excess production of lactic acid. Lactic acidosis may be secondary to shock, severe anemia, or hypoxemia. Inborn errors of carbohydrate metabolism produce a severe lactic acidosis (see Chapter 52). In diabetes mellitus, inadequate insulin leads to hyperglycemia and diabetic ketoacidosis (see Chapter 171). Renal failure (see Chapter 165) causes a metabolic acidosis because the kidneys are unable to excrete the acid produced by normal metabolism.