- Definition
- Pathophysiology
- Systems Affected
- Genetics
- Incidence/Prevalence
- Geographic Distribution
- Signalment
- Signs
- Causes
- Risk Factors
BASICS
- Free ammonia (NH3) is a nonprotein nitrogen compound that can permeate cells and result in hyperammonemia. At physiologic pH, almost all blood ammonia is the ammonium ion (NH4+), which is less permeable for cells. In order to eliminate waste nitrogen as ammonia, mammals convert it to an excretable form—urea. To a lesser extent, ammonia is eliminated by conversion to glutamine
- Reference intervals for plasma ammonia concentrations are dependent on the type of assay and reported units. Hyperammonemia occurs when concentrations exceed the established laboratory reference intervals
- The major source of blood ammonia is derived primarily from dietary nitrogen via the GI tract bacterial proteases, ureases, and amine oxidases
- Ammonia also may be derived from catabolism of glutamine and protein, and skeletal muscle exertion
- Ammonia is delivered to the liver via the portal vein or hepatic artery, where functional hepatocytes remove ammonia to form urea by means of the Krebs–Henseleit urea cycle
- Often, 70% of the liver mass has inadequate function before serum hyperammonemia is detected. If functional liver mass is inadequate, ammonia is not converted to urea, and plasma ammonia concentration increases. Urea concentrations also rise when glomerular filtration is inadequate. Acid–base status affects the absorption of ammonia
- As blood pH increases, free ammonia (NH3) increases and can permeate cells via nonionic diffusion to produce toxicity. Ammonia is one of the compounds responsible for clinical signs of hepatic encephalopathy
- Hyperammonemia has a toxic effect on neuron cell membranes by inhibition of ATP and alteration of the tricarboxylic acid cycle; both lead to neuronal cell energy depletion
- Other neurotoxins in hepatic encephalopathy are the result of—alterations in monoamine neurotransmitters due to altered aromatic amino acids, increased activity of GABA, glutamate receptor alterations, and increased endogenous benzodiazepine-like substances. Additionally, GI-derived neurotoxins are implicated, such as mercaptans, short-chain fatty acids, and phenols
- Nervous—ammonia is neurotoxic and the brain is affected by high plasma concentrations
- The degree of hyperammonemia does not necessarily correlate with the severity of hepatic encephalopathy signs since other compounds are involved. Ammonia interferes with the blood–brain barrier, cerebral blood flow, cellular excitability, neurotransmitter metabolism, and ratios of neurotransmitter precursor amino acids
- Degenerative changes of the neurons and supporting cells have been observed in chronically affected animals
- Clinical signs of hyperammonemia are primarily those of hepatic encephalopathy, although this is not the only substance responsible for clinical signs
- Signs may be sporadic, progressive, and worsen after feeding
Ptyalism, behavior changes, visual deficits (blindness), compulsive circling, pacing, anxiety, head pressing, stupor, coma, unusual positions/posture, sudden falling to the ground, violent thrashing.
Stunted growth, loss of body condition, poor hair coat, mentation changes and aberrant behavior. Similar findings as discussed in liver disease (e.g. icterus) may be observed, especially in horses with acute hepatitis. In animals affected chronically, neuronal degeneration occurs and signs become persistent.
- Liver disease resulting in inadequate functional mass. Hepatic encephalopathy is a prominent clinical feature of hepatic failure in the horse, and is associated with hepatitis and hepatic cirrhosis. Abnormalities of the urea cycle, abnormal portal blood flow, or any disorder that results in markedly impaired liver function can cause hyperammonemia
- Decreased functional hepatic mass can result from toxins such as pyrrolizidine alkaloids, excess iron, blue-green algae, mycotoxins, urea poisoning, ammonium salt fertilizers, and other hepatotoxic drugs or chemicals; infectious diseases such as Tyzzer's disease due to Clostridium piliforme in foals, virus-associated Theiler's disease; and syndromes including hyperlipidemia in ponies and occasionally in horses, with associated hepatic dysfunction
- Portosystemic shunts; acquired or congenital
- Intestinal hyperammonemia in the absence of liver disease is thought to occur when intestinal disease induces increased ammonia production by microflora and a concurrent increase in GI permeability
DIAGNOSIS
TREATMENT
MEDICATIONS
FOLLOW-UP
MISCELLANEOUS