The liver is critical for the removal of circulating toxins. When liver function fails due to disease there is an associated build-up of toxins, some of which can have substantial impacts on the nervous system. The compound of most interest has traditionally been ammonia. Ammonia is produced in the intestine, absorbed and cleared by the healthy liver, through conversion of ammonia to urea. When the clearance is impaired then ammonia levels rise, crossing the blood-brain barrier (BBB) where it is toxic to neurons, leading to a loss of neuronal energy (ATP).
There are other important biochemical processes that also contribute to the neurological signs of HE. Altered amino acid metabolism is also at play, with up-regulation of the so-called aromatic amino acids (such as phenylalanine, tryptophan, tyrosine) and down regulation of branched-chain amino acids (BCAAs, including valine, leucine and isoleucine). Disruption to the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate are also important.
A relatively common cause of HE is the ingestion of certain toxic plants, such as Crotalaria species (Kimberley Walkabout Disease) or Paterson’s Curse (Echium plantagineum).
Signs of HE
The signs may vary. They may be intermittent or continuous. There is usually altered mentation, from dullness through somnolence and possibly coma. Some horses may become aggressive to owners and other horses. Some will “head press”, may appear blind, and develop compulsive behaviour, such as aimless walking or circling. The suspicion is increased through measurement of blood ammonia levels, along with changes in hepatobiliary indicators.
Treatment and Outcome
The signs can potentially be reversed by reducing blood levels of ammonia and treating the liver dysfunction. Some liver diseases, if acute, can be successfully managed but many chronic diseases, such as ingestion of toxic plants. One approach to reducing ammonia levels is to acidify the colon by giving lactulose, causing ammonia inside the gut to be converted to the ammonium cation, which unlike ammonia cannot easily penetrate the intestinal barrier.
Diet is also helpful, with the ideal diet being high in carbohydrates, low in protein, and rich in branched-chain amino acids. Frequent feeding is also recommended to prevent fluctuations in blood glucose. Beet pulp, sorghum, bran and milo are feedstuffs that are rich in the beneficial branched-chain amino acids. Mixing molasses into the diet is also helpful.
Ultimately success requires treatment of the underlying liver disease. An ultrasound and liver biopsy are typically required.
Tags: Liver; Neurology