Page 687 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

652 SECTION | IX Gases, Solvents and Other Industrial Toxicants

VetBooks.ir ethanol (Berger and Ayyar, 1981). However, EG is is a consistent finding in animals producing urine (Grauer
et al., 1984; Thrall et al., 1984b). As mentioned
biotransformed to highly toxic metabolites that results in
previously, renal toxicity may also be due to the cytotox-
severe metabolic acidosis and acute renal failure, hall-
marks of EG poisoning (Thrall et al., 1984b; Dial et al., icity of other EG metabolites. Renal failure is evident
1994a,b; Davis et al., 1997). EG is initially oxidized by 36 72 h following ingestion in dogs and by 12 24 h
to glycoaldehyde by ADH, and glycoaldehyde is then following ingestion in cats. Anuria often develops
oxidized to glycolic acid, and then to glyoxylic 72 96 h after ingestion. The kidneys are often swollen
acid (Fig. 49.2). Glyoxylic acid is primarily converted to and painful, particularly in cats. The three stages of acute
oxalic acid but may follow other metabolic pathways; end EG toxicity may overlap depending on the amount of
products may also include glycine, formic acid, hippuric EG ingested. Delayed neurological symptoms, though
acid, oxalomalic acid, and benzoic acid. Oxalic acid uncommon, may present.
forms calcium oxalate crystals with calcium. Cats are
unusually sensitive to EG due to their high baseline pro-
duction of oxalic acid (LaKind et al., 1999). Early Laboratory Abnormalities
Abnormal laboratory findings can be divided into those
Mechanism of Action associated with early EG intoxication, which may be
related to the presence of EG per se or to its toxic meta-
EG and its first metabolite, glycoaldehyde, are mainly
bolites, and those associated with late EG intoxication,
responsible for CNS toxicity (LaKind et al., 1999). The
most of which are related to renal failure. Early abnormal-
accumulation of glycolic acid and glyoxylic acid leads to
ities are primarily due to the presence of acid metabolites
metabolic acidosis. Acidosis is also thought to lead to
of EG in the serum that result in metabolic acidosis and
altered levels of consciousness and cerebral damage. 2
include decreased plasma bicarbonate (HCO ) concentra-
Calcium oxalate crystal deposition in various organs is 3
tion and increased anion gap. In addition, hyperphospha-
widespread but is most severe in the kidney producing
temia may occur due to ingestion of a phosphate rust
renal damage. Renal toxicity may also be due to the cyto-
inhibitor present in some commercial antifreeze products
toxicity of other EG metabolites.
(Grauer et al., 1984; Connally et al., 1996). The decreased
plasma HCO 2 concentration can be seen as early as 1 h
3
Clinical Signs following EG ingestion. Metabolites of EG significantly
Initial symptoms (Stage I, 30 min to 12 h after ingestion) increase the pool of unmeasured anions and cause an
may be similar to drunkenness, but without the character- increased anion gap. The anion gap is increased by 3 h
istic breath odor of alcohol. EG also causes GI irritation after ingestion, peaks at 6 h after EG concentration, which
and high EG blood concentrations. Symptoms in Stage I peaks 1 6 h following ingestion. EG is usually no longer
include nausea, vomiting, ataxia and knuckling, muscle detectable in the serum or urine 48 72 h after ingestion
fasciculations, decreased withdrawal reflexes and righting (Thrall et al., 1982; Grauer et al., 1984; Dial et al., 1994a,
ability, hypothermia, and osmotic diuresis with resultant b). Kits (e.g., Ethylene Glycol Test Kit, PRN Pharmacol,
polyuria and polydipsia (Grauer et al., 1984; Thrall et al., Pensacola, Florida) are available that accurately estimate
1984b; Connally et al., 1996). As CNS depression blood EG concentrations with a minimum detection limit
increases in severity, dogs drink less but osmotic diuresis of 50 mg/dL, and the results correlate well with other
persists, resulting in dehydration. In dogs, CNS signs established methods of measuring EG concentrations such
abate after approximately 12 h, and patients may briefly as gas chromatography (Dasgupta et al., 1995), although
appear to have recovered. Cats usually remain markedly the presence of propylene glycol or glycerol in the blood
depressed and do not exhibit polydipsia. Animals may be may cause a false-positive test result. Ethanol and metha-
severely hypothermic. Stage II is characterized by pulmo- nol do not result in a false-positive test result. Cats may
nary toxicity. Symptoms may include tachycardia, tachyp- be intoxicated with a lethal dose of EG that is below the
nea, pulmonary edema, hyperventilation, and shallow and 50 mg/dL detectable level of the EG test kit. Therefore, if
rapid breathing. Over time, as a result of glycolic and the test kit is negative and historical findings as well as
glyoxylic acid accumulation during metabolism, profound clinical signs are compatible with EG ingestion, the rec-
acidosis will present. Glycolic acid accumulates because ommendation is to initiate appropriate therapy for EG
the lactic dehydrogenase enzyme that metabolizes glyco- intoxication as well as submit a serum sample to a refer-
lic to glyoxylic acid becomes saturated. As glycolic acid ence laboratory capable of determining a quantitative
is further metabolized to oxalic acid, which then crys- concentration.
talizes with calcium, hypocalcemia may occur along with Determination of serum osmolality is also useful for
the precipitation of calcium oxalate crystals in the kidney, diagnosing early EG toxicosis, although other osmotically
which will produce renal toxicity in Stage III. Crystalluria active, low-molecular-weight alcohols and glycols could