Page 551 - Small Animal Internal Medicine, 6th Edition

CHAPTER 33 Clinical Manifestations of Hepatobiliary and Pancreatic Disease 523

portovascular anomalies and severe primary hepatobiliary protein restriction just worsens the hyperammonemia in
disease with acquired shunting have been ruled out, con- these cases. Certain conditions are known to accentuate or
VetBooks.ir genital urea enzyme cycle deficiencies and organic acide- precipitate HE and should be avoided or treated aggressively
when detected (Box 33.2). In fact, in many cases it is the
mias, in which NH 3 cannot be degraded to urea, are
considered. HE has also been reported in congenital cobala-
important in triggering HE. It is particularly important to
min deficiency in dogs. Animals with systemic diseases precipitating factors (rather than the diet) that are most
having hepatic manifestations do not undergo sufficient loss identify and treat any concurrent inflammatory disease that
of hepatic mass or change in hepatic blood flow to develop can trigger HE episodes in susceptible individuals. Recent
signs of HE. work in humans, experimental animals, and dogs with spon-
The sources of increased blood ammonia levels in animals taneous disease has highlighted the importance of inflam-
with liver disease are outlined in Fig. 33.4 and include the mation and inflammatory cytokines in triggering HE. It is
following: known that clinically relevant episodes of HE in dogs and
cats with congenital or acquired PSS are often precipitated
• Small intestinal enterocyte catabolism of glutamine as not just by feeding but also by stress and infections, empha-
their main energy source sizing the role of hypermetabolism, inflammation, and
• Endogenous hepatic protein metabolism from excess breakdown of body protein in the development of HE. A
dietary protein, GI bleeding, or breakdown of lean body
mass
• Bacterial breakdown of undigested amino acids and BOX 33.2
purines that reach the colon
• Bacterial and intestinal urease action on urea, which Precipitating Factors for Hepatic Encephalopathy in
freely diffuses into the colon from the blood Susceptible Individual

It is very important to realize that the traditional view that Increased Generation of Ammonia in the Intestine
the toxins causing HE are predominantly of dietary origin is • High-protein meal (e.g., puppy or kitten food)
misleading; although the gut is an important source of NH 3 • Very poorly digestible protein reaching the colon and
in animals on high-protein diets, in many animals, particu- allowing bacterial metabolism to ammonia
larly those with protein-calorie malnutrition, endogenous • Increased glutamine metabolism in small intestine as
sources of NH 3 may be more important, and further dietary energy source from large meal or increased energy
requirements for digestion
• GI bleeding (e.g., bleeding ulcer in acquired shunts
with portal hypertension) or ingestion of blood
Ammonia derived from Hepatic transamination • Constipation (increases contact time between colonic
other organs: and deamination of bacteria and feces and therefore increases ammonia
Metabolism of body protein amino acids for energy
when in negative nitrogen balance or to make other amino production)
Accentuated by inflammatory acids when excess or • Azotemia (urea freely diffuses across colonic
disease and likely by poor quality amino membrane and is split by bacteria to ammonia)
cytokines/inflammatory mediators acids are fed
Increased Generation of Ammonia Systemically
• Transfusion of stored blood
• Catabolism, hypermetabolism, protein-calorie
malnutrition (increases breakdown of lean body mass
with release of NH 3 )
Liver • Feeding a poor-quality protein (excessive deamination
as protein is used for energy)
Effects on Uptake, Metabolism, and Action of Ammonia
in the Brain
• Metabolic alkalosis (increases amount of nonionized
NH 3 in circulation, which increases passage across
Gut derived ammonia: Bacterial degradation of blood-brain barrier)
Metabolism of glutamine undigested protein in • Hypokalemia (results in alkalosis with consequences
by small intestinal the colon (should be
enterocytes as their main minimal on a digestible previously outlined)
energy source (obligate) protein diet) • Sedatives or anesthetics (direct interaction with various
neurotransmitters)
FIG 33.4 • Estrus (may be caused by production of neurosteroids
Sources of ammonia that can contribute to hepatic with neurologic effects)
encephalopathy. Note that it is now believed that bacterial • Inflammation (inflammatory cytokines have been
degradation of undigested protein in the colon is not the implicated in having a direct central effect)
most important factor in dogs fed a normal diet.