Acid-Base

Metabolic acidosis of extrarenal origin is suggested by a large, negative urine anion gap, whereas metabolic acidosis of kidney origin is suggested by a positive urine anion gap.

Treatment of proximal renal tubular acidosis may require sodium bicarbonate, and the addition of a thiazide diuretic may be warranted.

Treatment of hypokalemic distal renal tubular acidosis includes correction of hypokalemia followed by administration of alkali therapy.

Ethylene glycol and methanol poisoning are characterized by a severe anion gap metabolic acidosis accompanied by an osmolal gap greater than 10 mosm/kg H2O (10 mmol/kg H2O).

Fomepizole is the agent of choice to inhibit alcohol dehydrogenase and prevent formation of toxic metabolites in patients with ethylene glycol and methanol poisoning.

An unexplained anion gap metabolic acidosis in the presence of recent acetaminophen ingestion should raise suspicion for pyroglutamic acidosis.

Saline-responsive metabolic alkalosis is characterized by a low effective arterial blood volume and a urine chloride level less than 15 meq/L (15 mmol/L).

Reassurance and rebreathing into a paper bag or other closed system are indicated for patients with respiratory alkalosis associated with the hyperventilation syndrome.

Serum bicarbonate concentrations higher or lower than the expected compensation suggest the presence of a mixed respiratory and metabolic acid-base disorder.

Patients with acute respiratory acidosis are primarily at risk for hypoxemia rather than hypercapnia or acidemia.

Correction of induced posthypercapnic metabolic alkalosis can usually be achieved with saline and discontinuation of loop diuretics if these agents are being used.

UAG = (Urine Na + Urine K) - Urine Cl

The UAG is normally between 30 to 50 meq/L (30 to 50 mmol/L). Metabolic acidosis of extrarenal origin is suggested by a large, negative UAG caused by significantly increased urine ammonium excretion. Conversely, metabolic acidosis of kidney origin is suggested by a positive UAG related to minimal urine ammonium excretion.

Proximal or type 2 RTA should be suspected in patients with a normal anion gap metabolic acidosis, a normal UAG, hypokalemia, and an intact ability to acidify the urine to a pH of less than 5.5 while in a steady state. In the steady state, the serum bicarbonate concentration is usually between 16 and 18 meq/L (16 and 18 mmol/L).

Proximal RTA can be an isolated finding but most commonly is accompanied by generalized dysfunction of the proximal tubule, which manifests as glycosuria, phosphaturia, uricosuria, aminoaciduria, and tubular proteinuria and is known as Fanconi syndrome (Table 10 ). Proximal RTA is not associated with nephrolithiasis or nephrocalcinosis. However, osteomalacia can develop as a result of chronic hypophosphatemia and/or deficiency in the active form of vitamin D. Patients with proximal RTA may develop osteopenia due to acidosis-induced demineralization of bone.

Correction of acidosis in patients with proximal RTA is often not possible even with administration of large amounts of sodium bicarbonate, because bicarbonate is rapidly excreted in the urine. In addition, this therapy accelerates kidney potassium losses. The addition of a thiazide diuretic may increase the efficacy of alkali therapy by inducing volume depletion, lowering the glomerular filtration rate (GFR) and thereby decreasing the filtered load of bicarbonate. The addition of a potassium-sparing diuretic may limit the degree of kidney potassium wasting. Once therapy is initiated, close monitoring of serum electrolyte levels is indicated to prevent severe derangements in these levels.

Hypokalemic distal RTA (type 1 RTA) should be considered in patients with a normal anion gap acidosis, hypokalemia, a positive UAG, and an inability to maximally decrease the urine pH; a urine pH greater than 5.5 in the setting of systemic acidosis is consistent with this condition

Patients with hypokalemic distal RTA frequently have nephrolithiasis and nephrocalcinosis. This predisposition to kidney calcification results from the combined effects of increased urine calcium excretion due to acidosis-induced bone mineral dissolution, a persistently alkaline urine pH, and low urine citrate excretion.

Administration of alkali therapy in an amount equal to daily acid production (usually 1 to 2 meq/kg daily) usually corrects the metabolic acidosis in patients with hypokalemic distal RTA. The potassium deficit should be corrected in these patients before correcting the acidosis. Potassium citrate is the preferred form of alkali therapy for patients with persistent hypokalemia or calcium stone disease.

Hyperkalemic distal RTA (type 4 RTA) should be suspected in patients with a normal anion gap metabolic acidosis associated with hyperkalemia and a slightly positive UAG (Table 12 ). Patients in whom this condition is caused by a defect in mineralocorticoid activity typically have a urine pH higher than 5.5.

• The primary goal of treatment in patients with hyperkalemic distal RTA is to correct the hyperkalemia. A decrease in the serum potassium level often results in correction of the acidosis by restoring kidney ammonium production and therefore increasing the buffer supply for distal acidification. Alkali therapy with sodium bicarbonate may treat the acidosis and hyperkalemia in patients with hyperkalemic distal RTA.
• Drugs known to interfere in the synthesis or activity of aldosterone should be discontinued. In patients who do not have hypertension or fluid overload, administration of a synthetic mineralocorticoid such as fludrocortisone is an effective treatment for aldosterone deficiency; in patients with hypertension, a thiazide diuretic would be an appropriate alternative treatment. In addition, loop diuretics are indicated in patients with an estimated GFR of less than 30 mL/min/1.73 m2; these agents increase distal sodium delivery, which stimulates potassium and hydrogen secretion in the collecting duct.

D-Lactic acidosis is a form of metabolic acidosis that can occur in patients who have the short-bowel syndrome, which may be caused by small-bowel resection or jejunoileal bypass surgery. In these patients, the colon receives large amounts of carbohydrates that are normally extensively reabsorbed in the small intestine. In the presence of colonic bacterial overgrowth, these substrates are metabolized into D-lactate and absorbed into the systemic circulation. Accumulation of D-lactate produces an anion gap metabolic acidosis that is associated with normal serum lactate levels, because the standard test for lactate is specific for L-lactate.

Patients with D-lactic acidosis typically seek medical attention after ingesting a high-carbohydrate meal and present with neurologic abnormalities such as confusion, slurred speech, and ataxia.

Management of this condition primarily involves sodium bicarbonate therapy for acute acidosis and a low-carbohydrate diet and antimicrobial therapy to decrease the degree of bacterial overgrowth.

Aspirin poisoning leads to increased lactic acid production. The accumulation of lactic acid, salicylic acid, ketoacids, and other organic acids results in an anion gap metabolic acidosis. Salicylates also have a concomitant direct stimulatory effect on the respiratory center. Increased ventilation lowers the arterial PCO2, which contributes to the development of a respiratory alkalosis.

Clinical manifestations of salicylate poisoning in adults may include tinnitus, tachypnea, tachycardia, excessive sweating, and nausea and vomiting. Patients with severe toxicity may develop hyperthermia, pulmonary edema, hematemesis, and mental status changes.

• In addition to supportive therapy, initial management of salicylate poisoning includes correcting the systemic acidemia and increasing the urine pH. Increasing the systemic pH leads to an increase in the ionized fraction of salicylic acid, which results in decreased accumulation of the drug in the central nervous system. An alkaline urine pH also favors increased urine excretion of the salicylate.
• Hemodialysis is warranted in patients with serum salicylate concentrations above 80 mg/dL (5.8 mmol/L) or in the setting of severe clinical toxicity.

Pyroglutamic acidosis occurs in critically ill patients who receive therapeutic doses of acetaminophen; in this setting, acetaminophen metabolism and oxidative stress associated with critical illness lead to a decrease in glutathione levels, which causes pyroglutamic acid to accumulate.

Pyroglutamic acidosis manifests as an anion gap metabolic acidosis accompanied by mental status changes ranging from confusion to coma. An unexplained anion gap metabolic acidosis in the presence of recent acetaminophen ingestion should raise suspicion for this condition.

Those who have a low EABV and Urine chloride < 15 mEq/L.

Isopropyl alcohol poisoning is characterized by an increased osmolal gap in the setting of positive serum and urine ketones and does not cause metabolic acidosis.

Toluene, an industrial solvent that can be abused as an inhalant, may cause confusion and disorientation in addition to metabolic acidosis, hypokalemia, hypophosphatemia, rhabdomyolysis, and elevated creatine kinase level.

The process for determining if a complicating metabolic disturbance is present along with an anion gap metabolic acidosis involves calculating the corrected bicarbonate level. If the corrected bicarbonate level is less than 24 ± 2 meq/L (24 ± 2 mmol/L), a coexisting normal anion gap metabolic acidosis is present; conversely, if the corrected bicarbonate level is greater than 24 ± 2 meq/L (24 ± 2 mmol/L), a coexisting metabolic alkalosis is present.The corrected bicarbonate level is obtained using the following formula:

Corrected HCO3 = [Measured HCO3] + [Anion gap - 12]