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Metabolic acidosis in poisoning. Taken from Metabolic acidosis: differentiating the causes in the poisoned patient B Judge Med Clinic N Am 2005, 89:1107. Metabolic acidosis. Definition: process that lowers serum HCO 3 -
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Metabolic acidosis in poisoning • Taken from Metabolic acidosis: differentiating the causes in the poisoned patient B Judge Med Clinic N Am 2005, 89:1107
Metabolic acidosis • Definition: process that lowers serum HCO3- • Occurs when H+ ion production exceeds body’s ability to compensate adequately via buffering or ventilation Mechanisms of metabolic acidosis in poisoning • Increased acid production • Impaired acid elimination
Calculations • Note the low pH (or high H+) • Then calculate Anion Gap (AG) AG = [Na+] – ([Cl-] + [HCO3-]) Usual range = 12 +/- 4 m/Eq/L (more recently 7 +/- 4) • If toxic alcohols suspected, calculate osmolality: 2 x [Na+] + [glucose] + [urea] and request a measured osmolality on a blood sample Osmol Gap = measured osmolality – calculated osmolality
AG & metabolic acidosis • High AG Occurs when an acid is paired with an unmeasured anion (eg lactate, formate) • Normal AG Occurs with gain of both H+ and Cl- ions, or a loss of HCO3- and retention of Cl-, preserving electroneutrality • However, AG can be affected by errors of calculation or assay, and by numerous disease states. So the lack of a high AG does not exclude any particular cause
Classical causes of high AG metabolic acidosis • Methanol • Uremia • Diabetic ketoacidosis, alcoholic ketoacidosis, starvation ketoacidosis • Paraldehyde • Iron, isoniazid • Lactic acidosis • Ethylene glycol • Salicylates
Common toxicological causes of high AG metabolic acidosis • Paracetamol • Amphetamines • Carbon monoxide • Cocaine • Toluene, benzene • Valproate • Salicylates • [NSAIDs, metformin, glycols] • [ARVs: Zidovudine, didanosine, stavudine]
Use of the osmol gap in patients with a high AG metabolic acidosis • Osmol gap may provide extra information if a toxic alcohol is suspected. • However, be aware that other medical conditions such as ketoacidosis and renal failure also cause a raised OG • Normal osmol gap = less than 10 +/- 6 mOsm/L • However, normal range has problems due to wide variability between people and assays
Toxins associated with a high osmol gap • Mannitol • Alcohols: ethanol, etylene glycol, isopropanol, methanol, propylene glycol • Diatrizoate (amidothizoate) • Glycerol • Acetone • Sorbitol
Ethylene glycol Glyceraldehyde Glycolate Glyoxylaye Oxalate Methanol Formaldehyde Formate Metabolism of toxic alcohols
The mountain Mycyk & Aks, 2003
Acetazolamide Acids (NH4 Cl, HCl) Cholestyramine Mg Cl Mafenide acetate Topiramate Ureteroenterostomy Diarrhoea Hyper-alimentation Pancreatic fistula Post-hypocapnia Rapid IV fluid administration Renal tubular acidosis Common causes of normal AG metabolic acidosis
Mechanisms of increased acid production • Toxins are acids (eg HCl vs. sulphuric acid) • Toxins have acid metabolites (eg metabolism of alcohols to acids) • Toxins affect ATP consumption/production in mitochondria (eg pcm, valproate, ARVs, metformin, CO, cyanide, formate, +++ adrenergic stimulation) [uncoupling oxidative phosphorylation or inhibiting cytochromes of the electron transport chain] • Toxins create ketoacids (eg ethanol, isoniazid)
Mechanisms of impaired acid elimination • Toxin metabolites damage kidneys (ethylene glycol) • Toxin causes distal RTA (eg toluene)
Treatment • Give supportive care and stop offending drug • HCO3- administration generally not recommended Appropriate for increasing poison elimination (eg salicylates) and countering Na channel block (eg TCA) • Consider antidotes where available (eg ethanol or fomepizole for toxic alcohol ingestion) • Thiamine, pyridoxine and folate for toxic alcohols