Lecture 3

Question 1

Ethylene Glycol (sources & toxicity)

Answer 1

Sources: Anti-freeze products, De-icers (products can be made by Propylene-glycol = less toxic, but expensive)
Most common: Oct-Nov, March-May. Less frequent in neutered animals
Dogs: LD50= 5 ml/kg
Cats: LD50= 1 ml/kg

Question 2

EG- TK

Answer 2

PO -> quick & complete absorption -> metabolism (liver) within 3h, good prognosis within 8-12 h, after that bad prognosis -> elimination of EG + toxic metabolites

Question 3

EG: Metabolism

Answer 3

EG, by alcohol DH -> Glycolaldehyde, by aldehyde DH ->
Glycolic acid + Glyoxylic acid (-> formic acid, Glycine. Life threatening: pH=6.5. Give B1 & B6 -> liver protection, Na-Carbonate -> neutralizes pH) + Oxalate -> Ca-Oxalate (= crystal -> damages tubular cells => acute tubulonephrosis & acute RF => oliguria, anuria, hyperkalaemia => cardiac arrest => death, uraemia, hypocalcaemia = seizures)

Question 4

Mechanism of effect & clinical signs

Answer 4

1. CNS signs (0.5-3 h): drunken animals, gastric irritation => vomiting, alcohol & aldehydes -> dizziness & ataxia!!!! (= 95% of signs).
   EG (M= 69000 D) -> incr osmolality => body tissues DH -> water in the blood -> RAAS deactivated => PU, PD, polyparesis, paralysis
2. Acidotic & CV effects (5-8 h): acidic metabolites (Glycolic acid) -> serious acidosis: HF => comatose state, Kaussmaul dyspnoe (labored breathing), tachypnoe, tachycardia (low contractility -> tries to compensate), HF (hypocalcaemia, acidosis, hyperkalaemia)
3. Renal insufficiency (9-12 h): Ca-Oxalate & acidosis -> damage the kidney (give Na-hydrocarbonate infusion -> protects kidney, heart, alkalizes).
   Nephrotoxicity -> Albuminuria, Haematuria (diagnose: infusion -> still empty bladder).
   Acute RF -> oliguria, anuria => uraemia, azotaemia -> lethargy, vomiting, ulcers (oral cavity & stomach -> haematemesis, melaena. Perfusion of the stomach wall is decreased & bicarbonate is produced => no protection), convulsions, tremors (CNS signs). Anterior Uveitis, haemorrhages in the vitreous humor (Ca-Oxalate -> eye -> damages inner bv -> blood, euthanasia is recommended)

(4. Ca-Oxalate -> brain vasculature => life long epilepsy if they survive stage 3).

Question 5

Pathology

Answer 5

1. Edema throughout the body
2. Acute Tubulonephrosis (multifocal degeneration, necrosis)
3. Uraemic signs (gastric ulcers, haemorrhagic gastritis)

Question 6

Diagnosis

Answer 6

Anamnesis (spring & autumn)
Wood lamp (UV-light: anti-freeze product contain fluorescent dye => check mouth for traces)
US, blood chemistry (high creatinine 1000mmol/L ppt of albumin -> centrifuge => crystals (immediate Ethanol treatment)
No time for GC, TLC (slow)
Colorimetric kits (blood sample -> croos reactions with propylene-glycol, Glycerine

Question 7

Treatment

Answer 7

1. Inducing emesis (xylazine, apomorphine- useless), adsorption (activated charcol PO- not effective), elimination (saline laxatives- too slow).
2. Fluid therapy ( RBF, GFR, Ringer Lactate= best!!, NaHCO3: Alkaligen infusion, protocol for anunria to initiate kidney function: why Mannitol is best? Osmotic diuretic because concentrated & cannot be reabsorbed, cannot croos biological membrane, only finest rated membr in the glomerulus so only present in blood & urine)
3. 20% Ethanol IV every 4-6 h, for 3 days= most important. It’s a competitive antagonist of EG for alcohol DH. Disadvantage: hepatotoxic, resp depression -> asphyxia, further incr osmolality (low BT => worse)
4. Fomepizole: inhibits alcohol DH (with no SE)
5. Supportive therappy: Glucocorticoids -> edemas, Ca-supplements 40-60 mg/kg, Omperazole IV (gastroprotectives), Thiamine & Pyridoxine 100 mg/animal (poor prognosis)

Question 8

Xylitol

Answer 8

1g can kill a 10kg dog, cats not really sensitive.
Causes serious hypoglycaemia, insulin trigger, hepatotoxic.
Clin.signs: ataxia, lethargy, incoordinated mvm, convulsions.

Treatment: Glucose IV every 4-6h (first: 20%, then 5%), hospitalization