Normal anion gap acidosis is also quite common in critically ill patients and may coexist with increased anion gap acidosis. It is characterized by hyperchloremia and is due to HCO3- loss and Cl- gain. Thus it is also called hyperchloremic acidosis. Normal anion gap acidosis can be classified by the presence or absence of normal urinary NH4+ excretion, which can be detected by calculating the urinary anion gap as follows:
urinary anion gup = ((Na" ] + [Kk ]) — [(11" ].
This value is negative in the presence of normal (unmeasured) NH 4+ excretion, as in diarrhea with gastrointestinal HCO3- loss. It is positive or neutral in the absence of renal acidification and NH4+ excretion. For example, this occurs with a distal renal tubular dysfunction due to mineralocorticoid defect. Thus calculation of the urinary anion gap is occasionally useful in assessing mixed or complex metabolic acidosis in the critically ill.
Proximal renal tubular acidosis is a rare cause of normal anion gap acidosis in the critically ill and is due to a defect in proximal tubule secretion of H + and reclamation of HCO3- (type II renal tubular acidosis) (.E,.m..m..eit.et§L 1992; Schmidt.1992.). Bicarbonate loss is offset by normal ammoniagenesis and NH4+ excretion. Proximal renal tubular acidosis may be due to HCO3- wasting in isolation or with other tubular resorption abnormalities (Fanconi syndrome), inhibition of carbonic anhydrase by acetazolamide, other disorders of amino acid and carbohydrate metabolism, Wilson's disease, myeloma (due to the toxic effects of Bence-Jones and other proteins on tubular cells), hyperparathyroidism, vitamin D deficiency, defects or inhibition by acetazolamide or Sulfamylon® of tubular carbonic anhydrase, and interstitial renal diseases (such as Sjogren's syndrome, amyloidosis, renal transplant rejection, and renal vein thrombosis).
Excessive loss of HCO3- in the gastrointestinal tract also causes normal anion gap acidosis. Bicarbonate is lost due to diarrhea, pancreatic or biliary fistulas, ureteric diversions to the gastrointestinal tract, particularly ureterosigmoidostomy, and vomiting in the presence of achlorhydria ( Emmett.et,a[, 1992.; Schmidi1992).
Less common causes of hyperchloremic acidosis with normal NH4+ excretion include recovery from chronic hypocapnia (associated with a HCO3- diuresis), administration of HCl and HCl precursors, such as NH4Cl and CT-containing amino acids in parenteral nutrition, and administration of large volumes of
HCO3--depleted solutions (such as normal saline) in the setting of volume contraction ( Emmettefal 1992).
Distal renal tubular acidosis is another uncommon cause of normal anion gap acidosis in the critically ill. It may be primary or secondary, due to familial hypercalciuria and nephrocalcinosis, hyperparathyroidism, hypervitaminosis D, hyperthyroidism, and tubular epithelial defects caused by drugs (such as amphotericin B, lithium, toluene, analgesics, particularly phenacetin and acetaminophen (paracetamol), and cyclamates). Tubulointerstitial defects, such as those occurring with polyclonal gammopathies, Sjogren's syndrome, chronic renal transplant rejection, chronic obstructive uropathy, and chronic active hepatitis, are important causes.
Hyperkalemic renal tubular acidosis is caused by a mineralocorticoid defect resulting from impaired adrenal gland aldosterone synthesis (i.e. adrenal insufficiency), reduced angiotensin II stimulation of aldosterone (as occurs in hyporeninemia in diabetes or pharmacological prostaglandin or angiotensin-converting enzyme inhibition), and renal resistance to mineralocorticoid (from receptor abnormalities, tubular destruction, or pharmacological interference by spironolactone, amiloride, and cyclosporin). In hyperkalemic renal tubular acidosis, reduced mineralocorticoid activity decreases Na + resorption and K+ and H+ secretion, which therefore causes impaired acid excretion, reduced tubular trapping of NH3 as NH 4+, volume depletion, and hyperkalemia.
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