Osmolality Case Study

Question 1

A garage mechanic was admitted to the emergency room unconscious, having been found in this state at home by his flat-mate. He had been acutely depressed since the death of his girlfriend in a road traffic accident two weeks before. On examination, he was not able to be
aroused. Temperature, blood pressure and pulse were normal but he was hyperventilating.
Investigations
Sodium 138 mmol/L
Potassium 5.2 mmol/L
Bicarbonate 4 mmol/L
Urea 7.0 mmol/L
Creatinine 110 umol/L
Glucose 4.5 mmol/L
Calcium 1.5 mmol/L
Osmolality 326 mmol/kg
(phosphate, protein, ‘liver function” tests were within reference intervals)
acetaminophen, salicylate: not detected
blood gases: PCO2 25 mmHg (reference 35-45)
Urine: negative: glucose and ketones
present: calcium oxalate crystals

1. Calculate the osmolal gap.
2. Based on the patients results what is the most probable diagnosis?
3. How would the patient be treated?

Answer 1

1. 38 or 49 (based on what formula you use)
2. There is a severe non-respiratory acidosis:diabetic ketoacidosis is excluded by the normal glucose and lack of ketonuria. The calculated osmolality is approximately 288 (or 277) mmol/kg, giving an osmolal gap of 38 (or 49) mmol/kg, suggesting the presence of some other osmotically active substance(s) in the blood. A lactate concentration this high in lactic acidosis would be exceptional. The substance could be ethanol (although the acidosis of ethanol poisoning is usually ketoacidosis) or some other alcohol. The clue to the diagnosis is provided by the low calcium concentration. The combination of severe acidosis and hypocalcaemia is characteristic of ethylene glycol poisoning. This substance is metabolized to various organic acids, including oxalic acid, which combines with calcium to form insoluable calcium oxalate.
3. Ethylene glycol is present in antifreeze products and is ingested either accidentally or for the purpose of inebriation or suicide. Ethylene glycol is relatively non-toxic and initially the CNS effects resemble those of ethanol. The metabolism of ethylene glycol by ADH results in the formation of a number of acidic metabolites including oxalic acid and glycolic acid. The clinical manifestations include neurological abnormalities (CNS depression, coma and convulsions), severe metabolic acidosis, acute renal failure and cardiopulmonary failure. Due to the rapid elimination of ethylene glycol (half-life of approx 3 hours), its serum concentration may be low or undetectable at a time when that for glycolic acid remains elevated. Therefore the determinations of both ethylene glycol and glycolic acid gives very useful clinical and information. Other clinical findings with ethylene glycol poisoning include increased serum osmolal and anion gaps, decreased serum calcium, and the presence of calcium oxalate crystals in the urine. The decreased serum calcium results from calcium oxalate deposition in tissues, from a possible interference in normal parathyroid hormone response, or both.
   The treatment for ethylene glycol intoxications includes the administration of ethanol to
   saturate ADH and thereby inhibit metabolism of ethylene glycol or the administration of the
   ADH inhibitor, 4-methylpyrazole (Antizol [fomepizole]), aggressive therapy with sodium
   bicarbonate to alleviate the acidosis, and hemodialysis or forced diuresis to enhance the
   removal of ethylene glycoland acid metabolites. A serum ethanol concentration of approx. 100 mg/dL is sufficient to saturate ADH and thus prolong the elimination half-life of ethylene glycol from approx. 3 hours (metabolism and renal excretion) to about 17 hours (renal excretion).
   Administration of ethanol or –methylpyrazole generally is recommended when the serum ethylene glycol is greater than 20mg/dL. When the serum ethylene glycol concentration is
   greater than 50 mg/dL hemodialysis will effectively remove ethylene glycol and glycolic acid. (or in severe cases of metabolic acidosis or vascular collapse).