Amin A. Nanji

Sensitivity and Specificity of Liver Function Tests in the Detection of Parenteral Nutrition-Associated Cholestasis

We carried out a study to determine which of the liver function tests was the most sensitive and/or specific in detecting parenteral nutrition associated cholestasis. The tests utilized were alkaline phosphatase, gamma-glutamyl transpeptidase, cholylglycine, sulfolithocholylglycine, and bilirubin. Fifty-nine patients with no prior evidence of liver dysfunction were studied. We found gamma-glutamyl transpeptidase to be the most sensitive (89.5%) and also the least specific (61.9% specificity). Specificity of gamma-glutamyl transpeptidase was improved when it was combined with alkaline phosphatase. We recommend the combination of these two enzymes as the most cost effective way of detecting parenteral nutrition-associated cholestasis.

Acute liver failure: a possible consequence of severe hypophosphatemia

A patient with acute liver failure, in whom no infectious, toxic, or other cause of hepatic damage could be found, developed severe hypophosphatemia along with hepatocellular necrosis. We propose that phosphate depletion may be responsible for the liver cell damage, as hypophosphatemia impairs tissue oxygenation and depletes cellular ATP.

Hypomagnesemia Associated with Gentamicin Therapy

Two patients developed symptomatic hypomagnesemia most likely secondary to gentamicin therapy. Both patients were on regular doses of the antibiotic and had hypokalemia and hypocalcemia secondary to hypomagnesemia. Mechanisms postulated for the occurrence of hypomagnesemia secondary to gentamicin therapy include drug-induced hyperaldosteronism and tubular toxicity. Patients on gentamicin therapy should have serum magnesium, calcium, and potassium levels monitored routinely.

Antibody interference with biochemical tests and its clinical significance.

Antibody interference with routine biochemical tests is becoming increasingly recognized as a cause of spurious results. It is important to recognize these interferences because inappropriate investigation may be instituted in response to the abnormal test result. The present review deals with the various biochemical tests in which antibody interference occurs. The tests include measurement of enzymes, hormones, immunoglobulins, vitamin B12, and a variety of other molecules and ions.

Drug-Induced Electrolyte Disorders

A wide variety of pharmacologic agents have been implicated in a number of electrolyte disorders. The present review focuses on abnormalities of sodium, potassium, calcium, magnesium, and phosphate. Several mechanisms are involved in the pathogenesis of these disorders. These involve stimulation and modulation of other hormones (e.g., antidiuretic hormone, renin-angiotensin system, parathyroid hormone), damage to renal tubules, and, in some cases, a combination of factors. Recognition of these abnormalities is important because their presence may be life threatening or may aggravate the side effects of the drug itself.

Ticarcillin associated hypokalemia

We evaluated the presence and degree of hypokalemia associated with ticarcillin disodium (ticarcillin) therapy in 16 patients. Four of these patients who received less than 10 grams of ticarcillin did not develop significant hypokalemia, but this condition developed in 6 of 9 patients receiving a daily dose of greater than 18 grams of this drug, and the mean urinary potassium was elevated in this group (mean = 78 mEq/24 hrs). The degree of hypokalemia was correlated with the volume status of the patient as judged by the serum urea nitrogen: creatinine ratio. A positive correlation (r = 0.66, p less than 0.05) was obtained between the two parameters. Hypokalemia did not develop in three patients with the syndrome of inappropriate secretion of anti-diuretic hormone who were receiving more than 18 grams of ticarcillin daily, indicating the absence of a stimulus for sodium conservation. Aggressive potassium and fluid replacement should be considered in patients with hypokalemia associated with ticarcillin therapy.

Ketone interference in estimation of urinary creatinine; effect on creatinine clearance in diabetic ketocidosis

Acetoacetate is known to spuriously raise serum creatinine concentration in patients with diabetic ketoacidosis. Its effect on urinary creatinine has not been studied. Since the renal threshold for ketoacids is low, large amounts of acetoacetate may be present in the urine of uncontrolled diabetics. We investigated this interference using three different automated analysers. We found that +3 or +4 reactions with Ketostix, equivalent to greater than 10 - 15 mmol/L of acetoacetate caused significant interference with the Abbott VP and Beckman Astra instruments. This could cause errors in the calculation of creatinine clearance especially when serum creatinine is close to a normal level. We recommend that measurement of creatinine clearance be delayed until better diabetic control is achieved or the creatinine be measured by a method which is free from ketone interference, e.g., by the Dupont aca.

Relationship between Serum Albumin and Parenteral Nutrition-Associated Cholestasis

In a prospective study of 59 patients receiving total parenteral nutrition we found that patients with low serum albumin were more likely to develop cholestasis than patients with normal serum albumin. Only 25% of patients with a normal serum albumin developed cholestasis. Seventy-nine percent of patients with low serum albumin (less than 3.5 g/dl) developed cholestasis (p less than 0.01). In those patients who developed cholestasis, there was a significant correlation (r = 0.63, p less than 0.01) between the serum albumin and the number of days after onset of total parenteral nutrition when cholestasis appeared. The role of hypoalbuminemia in the development of total parenteral nutrition-associated cholestasis deserves further study.

Artefactual decrease in total protein concentration in patients with monoclonal gammopathies: A method-dependent error

We found total protein estimates in patients with monoclonal gammopathies to be erroneously low when using the Cobas-Bio centrifugal analyzer. This problem occurred only when a serum-water blank was used. This probably results from the precipitation of these proteins under conditions of low ionic strength resulting in high blank readings. The problem can be avoided if a serum-saline blank is used.

Lactulose-induced hypernatremia.

We describe severe hypernatremia in a patient with hepatic encephalopathy, who was treated with lactulose. Lactulose produces hypernatremia via its osmotic effect and its degradation to organic acids. We recommend that patients who receive large quantities of lactulose and who lack access to free water have their electrolytes monitored and the dose tapered as quickly as possible.