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

III. Clinical Manifestations of Hepatic Insufficiency
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C . Hepatic Photosensitivity
Photosensitivity is the result of hypersensitivity to sunlight
induced by the presence of exogenous or of endogenously
produced photodynamic substances. Clinical signs develop
when photosensitive animals are exposed to light and are
caused by inflammation and necrosis of unpigmented skin
(photodermatitis). A distinction is made between sunburn
and photosensitization. Animals with unpigmented skin
that are maintained for long periods of time indoors and are
abruptly exposed to sunlight may sustain sunburn, which
is a direct response of the unpigmented and unprotected
skin to ultraviolet radiation (320 μ M). Photosensitization
is, characteristically, a more severe reaction caused by the
interaction of a photodynamic substance and solar radiation.
The effective wavelength of light causing photosensitization
is determined by the absorption spectrum of the
photosensitizing substance, which may extend into the
visible region of light. Sunburn and photosensitization
also differ in that sunburn apparently can develop in the
absence of molecular oxygen, whereas photosensitization
occurs only in the presence of molecular oxygen ( Cook
and Blum, 1959 ; Schothorst et al., 1970 ). With sunburn,
there is a characteristic delay between exposure to light
and the development of erythema of the skin, soreness, or
pruritus. With photosensitization, initial clinical signs may
be noted within minutes after exposure to sunlight.
In domestic animals, three forms of photosensitization
are recognized. Photosensitivity may occur when a photodynamic
substance not present normally in the diet is
ingested and absorbed. Examples are the ingestion of the
poisonous plants Hypericum perforatum (St. John’s wort,
Klamath weed) and Fagopyrum esculentum (buckwheat).
Photosensitization caused by administration of the parasiticide
phenothiazine also is a form of primary photosensitization.
The photosensitizing compound is phenothiazine
sulfoxide, which accumulates in the skin and in the aqueous
humor inducing keratitis. A second form of photosensitization
is caused by photosensitizing compounds that are
produced endogenously. Congenital porphyria (pink tooth)
of cattle is one of the best characterized examples in which
a marked increase in production of uroporphyrin I results
in deposition of the porphyrin in the teeth and bones, and
large quantities are excreted in the urine. The teeth and
urine readily fluoresce when exposed to ultraviolet light.
The photodermatitis and hemolytic anemia associated with
the disease are directly related to the photodynamic effects
of endogenous porphyrins ( Kaneko et al., 1971 ; Scott et al.,
1979 ). Other inherited forms of porphyria in domestic
animals (reviewed by Tennant [1998] ) are described in
Chapter 8 .
A third group of diseases associated with photosensitivity
are those that are secondary to hepatic disease (hepatic
photosensitization). Photodermatitis associated with both
acute and chronic liver disease is recognized primarily in
herbivorous animals. The photodynamic agent responsible
for hepatic photosensitivity is phylloerythrin, a porphyrin
derivative from chlorophyll ( Rimington and Quin
et al., 1934 ). Chlorophyll is converted to phylloerythrin
by microorganisms of the rumen or large intestine that
remove the magnesium atom from the chlorophyll molecule
and hydrolyze the phytyl and carboxy methoxy side
chains leaving the porphyrin nucleus of chlorophyll intact.
Phylloerythrin produced in the alimentary tract is excreted
primarily in the feces. A small fraction of the relatively
nonpolar phylloerythrin is absorbed into the portal circulation.
In normal animals, phylloerythrin is quantitatively
removed by the liver and excreted in the bile and does not
reach the peripheral circulation. Phylloerythrin may be
found in the bile and feces of herbivores that are consuming
chlorophyll-containing diets and may be demonstrated
in other species that ingest chlorophyll. The comparatively
large amount excreted by ruminants is attributed to
their frequently high chlorophyll intake and to the favorable
conditions for microbial production of phylloerythrin
within the gastrointestinal tract.
In hepatic insufficiency, phylloerythrin is incompletely
cleared from the hepatic portal circulation, enters the systemic
circulation, and ultimately accumulates in the skin.
In the superficial layers of the unpigmented skin, phylloerythrin
absorbs solar energy resulting in formation of free
radicals. Reactive oxygen species cause peroxidation of
cellular lipids and cellular components (e.g., lysosomes).
Inflammation and necrosis of the skin are the result of
direct oxidative injury and the secondary action of lysosomal
enzymes ( Slater and Riley, 1966 ). The critical
range of wavelengths (action spectrum) that result in photodermatitis
in hepatic photosensitivity was shown in geeldikkop
to be between 380 and 650 μ m (Riemershmid and
Quin, 1941) and in facial eczema between 400 to 620 σ m,
ranges that are consistent with the known absorption
spectrum of phylloerythrin.
The types of hepatic disease of ruminants and horses
that are associated with photosensitivity vary considerably,
but the effects attributable to the photodynamic action of
phylloerythrin are similar. The nature and severity of the
cutaneous lesions depend on the amount of phylloerythrin
in the skin and on the intensity and the duration of light
exposure. The most common site of photodermatitis in the
horse is the muzzle, which has a sparse protective covering
of hair and often is unpigmented. Unpigmented areas of
the distal extremities also are frequently affected ( Fowler,
1965 ; Tennant et al., 1973 ). In cattle, unpigmented areas
of the muzzle, back, escutcheon, and the lateral aspects of
teats are especially susceptible to photodynamic injury.
The areas of skin affected in sheep are those that
receive the greatest exposure to light and that lack protection
provided by black pigment or wool and include the
ears, eyelids, face, lips, and coronets ( Riemerschmid and
Quin, 1941 ). The first clinical signs of photodermatitis in