Poisons affecting the liver
The liver is a multifunction organ involved in metabolism and synthesis of essential compounds. As the first organ after the gut to receive ingested substances and because of its role in metabolism, it is at particular risk of damage from ingested poisons and their toxic metabolites. Poisons affecting the liver are discussed in this second article on poisons by organ system. Among the most readily accessible liver toxicants are xylitol and paracetamol, which are commonly available in the home. The mechanism of xylitol-induced liver toxicity is unknown, but paracetamol is metabolised to toxic metabolites when normal mechanisms are overwhelmed and/or inadequate. Various natural sources of hepatotoxins are also discussed including some mushroom species (e.g. some Amanita species and Gyromitra esculenta), some cyanobacteria (blue-green algae) and plants such as cycads which can be grown as houseplants. The mechanism of liver damage with these natural sources includes direct hepatotoxins and toxic metabolites. The management of toxic liver damage is generally supportive with gut decontamination where appropriate and liver protectants, such as acetylcysteine and S-adenosyl-L-methionine (SAMe).
The liver is an amazing organ. It performs hundreds of essential functions including metabolism (of fats, proteins and carbohydrates), detoxification, synthesis of plasma proteins (albumin, globulins and coagulation proteins), storage of glycogen and gluconeogenesis (the generation of glucose from non-carbohydrate substrates), immunological functions and the synthesis of many essential compounds. The liver is at particular risk of the effects of poisons because it is one of the first organs exposed to ingested substances and is the major metabolising organ of the body.
Liver damage from poisoning can occur through various mechanisms. Some substances contain hepatotoxic substances or compounds that are metabolised to hepatotoxic chemicals. In some cases the mechanism of liver toxicosis is unknown. In the second article looking at poisons by organ system we discuss some poisons that affect the liver.
Xylitol has been much in the news lately and is well recognised as causing liver failure, although the mechanism of liver damage remains unknown. It may be due to prolonged adenosine triphosphate (ATP) depletion from xylitol metabolism resulting in cellular necrosis or production of reactive oxygen species that damage cell membranes and macromolecules (Dunayer and Gwaltney-Brant, 2006). In addition to liver damage, xylitol also causes hypoglycaemia as it is a potent stimulator of insulin release in dogs and this causes a decrease in blood glucose. A dose of 0.05 g/kg (50 mg/kg) xylitol can cause hypoglycaemia in dogs and more than 0.5 g/kg (500 mg/kg) can cause liver failure (Dunayer, 2006), although this may be idiosyncratic rather that a dose-related effect (Dunayer, 2006) since not all dogs that ingest more than 0.5 g/kg develop liver failure (Piscitelli et al, 2010). It is important to note that liver failure can occur in the absence of, or lack of diagnosis of, hypoglycaemia.