Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 13 Hepatic Function
sheep may be apparent restlessness with shaking of the
head or rubbing of affected parts. Individual animals may
seek relief in the shade. Erythema and edema are the first
cutaneous manifestations of photosensitization. Swelling
of the lips, ears, and face have led to the descriptive terms
“ big head ” and “ facial eczema. ” Following edema, serum
may ooze from damaged skin. Ultimately, second- or
third-degree burns may develop, and the morbidity and
mortality attributable to lesions of the skin may be more
important than any other aspect of the underlying liver disease
( Riemerschmid and Quin, 1941 ). In the early stages
of the disease, Southdown sheep with congenital photosensitivity
have no morphological abnormalities of the liver,
but the photodermatitis that is observed as soon as affected
lambs begin to consume green plants is associated with
significant biochemical defects in hepatic organic anion
excretion (Cornelius and Gronwall, 1968).
D . Ascites
The clinical sign of ascites is the result of abnormal accumulation
of fluid in the peritoneal cavity. In normal animals,
there is significant bidirectional movement of fluid,
electrolytes, and, to a lesser degree, protein across mesenteric
capillaries, through the interstitial space, and across
the peritoneal mesothelium into the abdominal cavity. Such
movements are determined by osmotic and hydrostatic
forces that are described by Starling’s equation: plasma
colloidal osmotic pressure minus ascitic fluid colloidal
osmotic pressure equals portal capillary pressure minus
intra-abdominal hydrostatic pressure. Normal portal capillary
pressure on the arterial side of the capillary bed favors
formation of an ultrafiltrate of plasma, which is nearly
protein free. On the venous side of the capillary bed, reabsorption
of interstitial fluid occurs because the hydrostatic
pressure is below that of the colloidal osmotic pressure primarily
exerted by plasma proteins within the capillary bed.
Under normal conditions, only a small volume of free fluid
is present in the peritoneal cavity.
During investigation of the mechanical factors that
influence formation of lymph, Starling (1894) observed
that obstruction of hepatic venous flow by ligation of the
thoracic vena cava cranial to the site of entry of the hepatic
veins produced significant increase in lymph flow through
the thoracic duct, and the lymph was high in protein.
Obstruction of the hepatic portal vein as it entered the liver
also increased the flow of thoracic duct lymph, but the
protein content was found to be low. Starling concluded
that the increased flow of thoracic duct lymph following
ligation of the thoracic vena cava arose from hepatic
lymph, and after ligation of the portal vein, increased thoracic
duct lymph was derived from mesenteric capillaries.
Hepatic lymph is produced primarily in the sinusoids
and contributes 25% to 50% of lymph flow in the thoracic
duct ( Brauer, 1963 ). In the dog and other species, hepatic
lymph has a much higher protein content than lymph from
other tissues because hepatocytes are not associated with
a conventional basement membrane and because of the
unique permeability of the sinusoids to plasma proteins
because of fenestrations between the endothelial cells that
line the sinusoids (Bissel and Maher, 1996). In experimental
cirrhosis in the dog and other species, the flow rate of
thoracic duct lymph is increased two to five times and the
protein content is higher than that of lymph derived from
other tissues ( Nix et al., 1951a, 1951b ).
Ascites caused by cirrhosis of the liver may be associated
with increased portal vein pressure (portal hypertension).
Experimental ligation of the portal vein before it
enters the liver, however, results only in minimal and transient
ascites or no ascites ( Schilling et al., 1952 ; Volwiler
et al., 1950 ). In the dog, ligation of either the hepatic vein
( Orloff and Snyder, 1961a, 1961b ; Orloff et al., 1963,
1964a, 1964b, 1966 ) or the caudal vena cava at a site cranial
to entry of the hepatic vein ( Berman and Hull, 1952 ;
Schilling et al., 1952 ; Witte et al., 1968, 1969a, 1969b )
produces prompt and intractable ascites. Lymph fluid
has been observed to form droplets said to “ weep ” from
the surface of the liver following experimental obstruction
of hepatic vein outflow ( Hyatt et al., 1955 ). Because
of its origin as hepatic lymph, the protein content of such
ascitic fluid may be 3.0 to 3.5 g/dl or higher. This observation
is consistent with the finding that the protein content
of ascitic fluid in the initial stages of cirrhosis may
be higher than that of conventional transudates (a modified
transudate) because of its hepatic origin. As progressive
fibrosis and “ capillarization ” of the hepatic sinusoids
develop ( Bissell and Maher, 1996 ), the protein content of
hepatic lymph decreases and correspondingly the protein
content of ascitic fluid decreases. It is probable in cases of
cirrhosis that there is increased production of both hepatic
lymph and mesenteric lymph and that ascites develops
when lymph from both sources fails to return to the systemic
venous circulation ( Witte et al., 1971a, 1971b ). The
protein content of ascitic fluid is influenced not only by the
relative proportions of mesenteric and hepatic lymph but by
the protein concentration of plasma. In advanced cirrhosis,
when hypoalbuminemia may be present, the protein content
of ascitic fluid can be expected to be proportionately low.
Although experimental portal vein obstruction per se
does not result in ascites, only transient portal hypertension
is actually produced by this procedure. When persistent
portal hypertension is produced experimentally
by aortic-portal anastomosis or when such anastomoses
occur congenitally, the ascitic fluid is characteristically
low in protein content because of its origin in mesenteric
capillaries.
Serum albumin is synthesized exclusively in the liver
and is the major determinant of plasma and tissue fluid
oncotic pressure. Hypoalbuminemia associated with