Hyperammonemia (HA), commonly defined as blood ammonium (NH4+) concentration higher than 60 µmol/L, can develop by increased production, increased absorption, decreased clearance, or a combination of these mechanisms. Hyperammonemia in horses has most frequently been associated with decreased clearance of NH4+ secondary to severe hepatic disease with subsequent development of hepatic encephalopathy. More recently, a different syndrome of increased blood NH4+ concentrations in the absence of hepatic disease has been recognized clinically and documented in the equine literature. The increased NH4+ concentrations are thought to originate from the gastrointestinal tract, and the syndrome is therefore referred to as intestinal HA. Intestinal HA is presumed to be caused by either overgrowth of urease-producing bacteria in the large or small intestine or increased absorption of NH4+ from the gastrointestinal tract because of altered permeability of the intestinal barrier.
Ammonium ion is primarily produced in two organ systems: the liver and the intestine. The NH4+ released by deamination of amino acids is quickly converted into urea by the liver and, to a limited degree, the kidney, thereby minimizing exposure of the body to the potentially harmful substance. In the intestine, NH4+ can be produced by breakdown of urea, luminal amino acids, or proteins by urease-producing bacteria. This occurs mainly in the large intestine, but cases of HA in horses with predominately small intestinal disease have also been observed. Urease-producing bacteria include many Enterobacteriaceae, in particular Proteus mirabilis, Pseudomonas spp, Klebsiella spp, Staphylococcus spp, Corynebacterium spp, Ureaplasma urealyticum, and Proteus penneri. Apart from two horses with intestinal HA, in which Clostridium sordellii was isolated in one horse and Clostridium perfringens was isolated in the other, no other potential pathogens have been identified in horses with intestinal HA.
The syndrome has been reported in a variety of horse and pony breeds across all age groups, including neonates. Most commonly, individual horses are affected, but small outbreaks involving multiple animals have been reported anecdotally. No consistent predisposing factors have been identified so far. The case history is often nonspecific, but gastrointestinal disease, such as colic, diarrhea, or both, as well as depression and fever are frequently described. Clinical signs are often suggestive of large or small intestinal disease with moderate to severe cardiovascular compromise; however, occasionally no obvious signs of intestinal involvement are apparent. Neurologic signs can be present during the first evaluation, develop during the course of the disease, or might be the only clinical signs. Ataxia, central blindness, aimless wandering, head pressing, salivation, bruxism, sudden aggression, violent behavior, compulsive walking and circling, grand mal seizures, collapse, and recumbency have all been reported. Laboratory findings include hemoconcentration, azotemia, severe metabolic acidosis with often dramatically increased blood lactate concentrations, hyperglycemia, and electrolyte abnormalities. Hypocalcemia has been reported and can be associated with synchronous diaphragmatic flutter. Other abnormalities indicative of severe gastrointestinal disease, such as leukopenia, hypoproteinemia, and coagulopathies, are also common. Postmortem examination might reveal no or very few gross and histologic lesions in any organ system or may reveal severe gastrointestinal pathology such as ulcerative or necrotizing colitis. It is conceivable that horses with few organ lesions might have had primary bacterial overgrowth, whereas horses with severe gastrointestinal lesions developed HA secondary to increased intestinal permeability.