Biomedical Engineering Reference
In-Depth Information
accidental ingestion or as a substitute for EtOH. Patients often present
with central nervous system (CNS) depression, metabolic acidosis,
ocular toxicity, regional brain damage (primarily in the putamen), and
death (Suit and Estes, 1990). Plasma concentrations of MeOH and its
metabolite FA of the patients are often measured and monitored upon
arrival at the hospital and throughout treatment. Metabolic acidosis due
to FA accumulation, as indicated by a lower blood pH, is believed to be
the cause of ocular toxicities and death in humans. This deviation from
normal physiological pH disrupts the anion gap and inhibits cytochrome
oxidase on the mitochondrial membrane, localized in the optic nerve
and retina (Baumbach et al., 1977; Hayreh et al., 1977). FA inhibits
cytochrome oxidase when at concentrations between 5 and 30mM,
which overlaps with concentrations observed in patients demonstrating
acute MeOH intoxication (Nicholls, 1975, 1976). If cells are
sufficiently damaged, swelling and edema result, which can compress
the optic nerves and potentially lead to cell death. As metabolic acidosis
worsens, further symptoms may include shallow respiration, cyanosis,
coma, and electrolyte disturbances, which eventually lead to death (Suit
and Estes, 1990). The blood MeOH concentration required to cause
these acute effects vary, but has been reported to fall within the range of
6-16mM for CNS effects, 16-47mM for ocular toxicity, and 42-
62mM for fatalities (IPCS, 1997) (Figure 7.12). These concentrations,
however, are an inaccurate representation of the actual blood levels
required to cause these acute effects of MeOH toxicity, as several
factors must be taken into consideration: (1) the amount and composi-
tion of the ingested MeOH solution is unknown; (2) the time since
initial ingestion is unknown, and therefore it is unknown how much of
the MeOH has already been metabolised; and (3) patients will receive
some form of intervention to alleviate the symptoms of MeOH poison-
ing. This includes treatment with EtOH, which acts as a competitive
inhibitor of ADH1 owing to its higher affinity than MeOH for the
metabolizing enzyme, ADH1 (Mani et al., 1970; Ekins et al., 1985). By
saturating ADH1, further metabolism of MeOH and the subsequent
acute toxicities due to FA accumulation are inhibited. Hemodialysis,
treatment with bicarbonate for acidotic patients, or treatment with drugs
