Page 491 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Fluid, Electrolyte, and Acid-Base Disturbances in Liver Disease 479

BOX 19-2 Putative Hepatoencephalopathic Toxins and Their Mechanisms

Ammonia Altered Neuroreceptors
þ
þ
# Microsomal Na ,K -ATPase in the brain Abnormal mediators and response
# ATP availability (ATP consumed in glutamine production) " Production false neurotransmitters
" Excitability (if mild " NH 3 ) Methionine ! Toxic Metabolites: Mercaptans
Disturbed malate-aspartate shuttle: # energy
(Methanethiol and dimethyldisulfide)
# Glycolysis
Synergistic with other toxins: NH 3 , SCFA
Brain edema (acute liver failure)
Gut derived ! fetor hepaticus (distinct breath odor in HE)
# Glutamate, altered glutamate receptors
# NH 3 detoxification in brain
" BBB transport: glutamate, tryptophan, octopamine þ þ
# Microsomal Na ,K -ATPase
Bile Acids Tryptophan
Membranocytolytic effects alter cell or membrane
Directly neurotoxic
permeability
" Serotonin: neuroinhibition
BBB more permeable to other HE toxins
Impaired cellular metabolism because of cytotoxicity Glutamine
Alters BBB amino acid transport
Endogenous Benzodiazepines NH 3 transfer
Neural inhibition: hyperpolarize neuronal membrane
Induction of peripheral (mitochondrial) benzodiazepine SCFA
receptors # Microsomal Na ,K -ATPase in brain
þ
þ
Uncouples oxidative phosphorylation
GABA Impairs oxygen use
Neural inhibition: hyperpolarize neuronal membrane Displaces tryptophan from albumin !"free tryptophan
" BBB permeability to GABA in HE
Phenol (Derived from Phenylalanine and
# a-Ketoglutarate: impairs energy metabolism, NH 3
detoxification Tyrosine)
Diversion from TCA cycle for NH 3 detoxification Synergistic with other toxins
# ATP availability # A multitude of cellular enzymes
Aromatic Amino Acids Neurotoxic and hepatotoxic
# Neurotransmitter synthesis: # dopa False Neurotransmitters (Tyrosine !
# Gluconeogenesis: compete with BCAA for CNS transporter Octopamine, Phenylalanine !
Accumulation of octopamine, phenylethanolamine, Phenylethylamines)
Serotonin Impair norepinephrine action
Octopamine and phenylethanolamine compete with dopa,
Norepinephrine

ATP, adenosine triphosphate; BBB, blood-brain barrier; HE, hepatic encephalopathy; GABA, g-aminobutyric acid; TCA, tricarboxylic acid;
BCAA, branched chain amino acids; CNS, central nervous system; SCFA, short-chain fatty acids.

CLINICAL MANAGEMENT NUTRITIONAL CONSIDERATIONS IN
OF PATIENTS WITH LIVER LIVER DISEASE
DISEASE The primary goal of nutritional support is to achieve pos-
itive (or at least neutral) nitrogen balance and to provide
Important therapeutic considerations in the patient with adequate energy, vitamin, and micronutrient intake.
liver disease include provision of appropriate nutrition for Protein and Sodium Intake
the stage of disease including assessment of protein and
sodium tolerance, as well as maintenance of euglycemia, Protein intake should be restricted only in the presence of
hydration, and electrolyte balance. Circumstances that hyperammonemia, ammonium biurate crystalluria, or
promote development of HE should be avoided, and clinically apparent HE or as a therapeutic trial when subtle
HE should be treated aggressively if it does develop. clinical signs suggest occult HE. In the latter situation,
Therapy to eliminate or ameliorate ascites should be car- protein intake should be increased cautiously according
ried out as necessary, and coagulation abnormalities to individual patient tolerance so as to avoid inadequate
should be identified and managed. nutrition. Nitrogen tolerance is estimated based on