Page 1121 - Small Animal Clinical Nutrition 5th Edition

Hepatobiliary Disease 1167

VetBooks.ir Table 68-6. Metabolic alterations in hepatic failure.* Mechanisms

Alterations
Portosystemic shunting
Hyperglucagonemia
Impaired hepatic degradation
Increased plasma aromatic amino acid levels
Hyperammonemia
Hyperinsulinemia Increased peripheral insulin resistance
Decreased insulin to glucagon ratio
Impaired hepatic degradation
Increased plasma cortisol levels Deranged feedback mechanism
Decreased liver and muscle carbohydrate stores Accelerated glycogenolysis
Impaired glycogenesis
Increased gluconeogenesis Hyperglucagonemia
Hyperglycemia (fasting and postprandial) Portosystemic shunting
Increased gluconeogenesis
Decreased insulin-dependent glucose uptake
Decreased insulin-hepatic glycolysis
Increased plasma aromatic amino acid levels Decreased hepatic clearance and incorporation into
proteins
Increased release into the circulation
Decreased plasma branched-chain amino acid levels Hyperinsulinemia and excessive uptake
Increased usage as an energy source
Increased plasma methionine, glutamine, asparagine and histidine levels Decreased hepatic clearance

*Adapted from Marks SL, Rogers QR, Strombeck DR. Nutritional support in hepatic disease. Part I. Metabolic alterations and nutritional
considerations in dogs and cats. Compendium on Continuing Education for the Practicing Veterinarian 1994; 16: 972.

the type of hepatic failure present. In health, the AAA (i.e., ty- occur in dogs with PSS (Rothuizen and Mol, 1987). Attempts
rosine, phenylalanine and tryptophan) are efficiently extracted to show that normalization of the BCAA:AAA ratio in cere-
from the portal circulation and metabolized by the liver. Re- brospinal fluid would restore dopaminergic inhibition at the
duced liver function is associated with an increase in circulating pituitary level have failed in dogs with induced HE (Meyer,
levels of AAA because of continued mobilization of amino 1998a).
acids for gluconeogenesis and impaired hepatic AAA metabo-
lism (Center, 1996; Strombeck and Rogers, 1978). Plasma con- Lipid Alterations
centrations of BCAA (i.e., leucine, isoleucine and valine), and Lipid metabolic processes in the liver include: 1) fatty acid and
most other amino acids metabolized in peripheral tissues are triglyceride synthesis, 2) phospholipid and cholesterol synthe-
reduced because of an increased rate of usage by muscle and sis, 3) lipoprotein metabolism and 4) bile salt synthesis. The
adipose tissue (Center, 1996; Strombeck and Rogers, 1978). liver synthesizes fatty acids from carbohydrate precursors by
The molar ratio between BCAA and the AAA (BCAA:AAA converting these precursors to acetyl-CoA. Fatty acids are gen-
ratio) in healthy dogs usually ranges between 3.0 to 4.0. This erally stored in the liver as triglycerides. After hepatic glycogen
ratio is often reduced to 1.0 or less in dogs with portosystemic stores are depleted, fatty acids are mobilized from adipose tis-
vascular anomalies and chronic hepatitis (Meyer, 1998; Center, sue and their rate of hepatic oxidation increases. The ketone
1996e; Strombeck et al, 1983, 1984; Rutgers et al, 1987). Con- bodies produced are an important energy source for peripheral
versely, massive, acute hepatic necrosis in dogs (which is a rare tissues (i.e., brain, skeletal muscle) and decrease the rate of glu-
disorder in dogs and cats) increases the plasma concentrations cose usage.
of all amino acids except arginine (Strombeck and Rogers, The liver is a site for β-oxidation of fatty acids, producing
1978). Increased circulating catecholamines, insulin and energy from fatty acid substrates (Chapter 5 and 6). L-carni-
glucagon concentrations are thought to contribute to the al- tine functions to transport long-chain fatty acids across the
tered amino acid metabolism seen in patients with liver disease inner mitochondrial membrane to the mitochondrial matrix
(Center, 1996; Strombeck et al, 1983). Because all neutral for β-oxidation.The liver is also a major site of cholesterol syn-
amino acids (which includes BCAA, AAA and glutamine) use thesis from acetyl-CoA. Cholesterol is found throughout the
the same carrier to cross the blood-brain barrier, the decreased body as a structural component of cell membranes, a substrate
BCAA:AAA ratio is even more pronounced in cerebrospinal for synthesis of steroid hormones and is important in the liver
fluid than in plasma. Alterations in plasma amino acid profiles as the precursor for bile acid synthesis. The liver secretes
may also play a role in the pathogenesis of HE (Fischer et al, lipoprotein particles and is an essential organ for their uptake
1975; Maddison,1992; Meyer,1998a).Increased cerebral AAA and metabolism.
levels have been hypothesized to form “false neurotransmit- The composition of plasma lipids and lipoproteins is altered
ters,” leading to decreased dopaminergic tone. Dopaminergic in patients with liver disease. These abnormalities are associat-
disinhibition at the pituitary level has been documented to ed with changes in lipoprotein and cholesterol synthesis, lec-