Transcript Metabolic Acidosis

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
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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
Metabolism of toxic alcohols
• Ethylene glycol
• Methanol
• Glyceraldehyde
• Formaldehyde
• Glycolate
• Formate
• Glyoxylaye
• Oxalate
The mountain
Mycyk & Aks, 2003
Common causes of normal AG metabolic
acidosis
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Acetazolamide
Acids (NH4 Cl, HCl)
Cholestyramine
Mg Cl
Mafenide acetate
Topiramate
Ureteroenterostomy
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Diarrhoea
Hyper-alimentation
Pancreatic fistula
Post-hypocapnia
Rapid IV fluid
administration
• Renal tubular 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