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

III. Fat-Soluble Vitamins
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doses of retinoids, epithelial cells undergo a “ terminal differentiation.
” Epithelial cells lose their normal columnar
shape, become flattened or squamous, and increase their
cytosolic content of keratin (stabilized by transglutaminase
catalyzed cross-links).
In dermis, this process normally results in a protective
outer layer, scales, and other specialized surfaces. With
a deficiency, however, the skin can thicken and become
hyperkeratinized. If the primary function of the epithelial
cell is the provision of a moist surface or absorption (e.g.,
an enterocyte or lung secretory cell), squamous hyperkeratinization
leads to loss of functional integrity. Lack of
protective mucus secretions sets the stage for infections
of the lungs and other tissues that depend on a mucus barrier.
In the intestine, hyperkeratinization induces premature
sloughing of enterocytes and malabsorption. The gradient
delivery of retinoids to epithelial cells helps to explain
why some epithelial cells undergo terminal differentiation,
whereas others undergo cell cycling and periodic turnover,
although important details need to be resolved. Other cells
that are responsive to retinoids include phagocytic cells
and cells associated with the immune response (e.g., the
normal proliferation of the B cells and T cells requires
vitamin A) ( Ross et al., 2000 ).
6 . Requirements
For any given animal, the requirement for vitamin A depends
on age, sex, rate of growth, and reproductive status. For optimal
maintenance, the allowance for many animals ranges
from 100 to 200 international units per kilogram of body
weight per day (one international unit is equal to 0.3 μg of
retinol). In young growing animals, a more precise method
of expressing the vitamin A requirement is on an energetic
basis. In animal feeds, 4000 to 10,000 international units per
kilogram of feed is considered adequate in the United States
to provide vitamin A requirements for most animals.
Pathological conditions that influence vitamin A status
include malabsorption, including pancreatic insufficiency
and cholestatic disease, cystic fibrosis, liver disease, and
kidney disease. Many forms of liver disease interfere with
the production or release of RBP, which results in a lower
plasma level of vitamin A. Renal failure can result in loss of
RBP in urine. Factors that impair lipid absorption and transport
might also be expected to influence vitamin A status.
7 . Evaluation of Vitamin A Status of Animals
The vitamin A status of animals may be evaluated on the
basis of physiological, clinical, and biochemical procedures.
Clinical testing for night blindness and the elevation
of CSF pressure has been used to indicate vitamin A status.
The concentration of retinol and its esters is readily measured
in biological samples by HPLC using various detectors
and indicates the vitamin A status. As the concentration
of retinol in plasma is well maintained until liver reserves
are depleted, plasma retinol is not an index of vitamin A
reserves. The latter is best provided by analysis of liver
biopsy samples. In many carnivores, the plasma contains, in
addition to retinol, equal or greater concentrations of retinyl
palmitate and retinyl stearate bound to albumin, the immunoglobulin
fraction, or to VLDL. Plasma retinol concentrations
in excess of 30 μ g/dl generally indicate that vitamin
A is not limiting. In most species, liver concentrations of
100 μ g of retinol/g liver are generally adequate.
8 . Pharmacology and Toxicity
Vitamin A and various retinoids are used increasingly
to treat skin disorders (acne and psoriasis) and certain
forms of cancer. A vitamin A responsive dermatosis in
cocker spaniels is well recognized and has been previously
described ( Scott, 1986 ). Retinyl- β -glucuronide and
hydroxyethyl retinamide are commercial preparations of
retinoids that have such activity but are less toxic than retinoic
acid. The mechanisms by which these agents function
most probably relate to the complex pathways involved in
epithelial and epidermal cell differentiation.
Vitamin toxicities may be classified under three broad
categories: acute, chronic, and teratogenic. When a single
dose of vitamin A (greater than 100 mg) is injected into
animals (20 to 50-kg weight range), symptoms such as nausea,
vomiting, increased cerebral spinal fluid pressure, and
impaired muscular coordination result. A lethal dose of vitamin
A (100 mg) given to young monkeys has been reported
to cause coma, convulsions, and eventual respiratory failure.
Chronic toxicity may be induced by intakes of vitamin
A in amounts 10 times the normal requirements. Doses of
vitamin A in this range can lead to alopecia, ataxia, bone
and muscle pain, and purities. Although cats have a high
tolerance to excessive intakes of vitamin A, hypervitaminosis
A occurs in cats that are given a diet largely of liver.
Affected cats exhibit skeletal deformations, particularly
exostoses of the cervical vertebra, which precludes effective
grooming. Vitamin A is also a powerful teratogen. A
single large dose during pregnancy (in the 50- to 100-mg
range) for an animal weighing 20 to 50 kg can result in
fetal malformations. Chronic intakes (exceeding 10 times
the requirements for given animals) can also be teratogenic.
Carotenoids, unlike retinoids, are generally nontoxic,
and many animals routinely ingest gram amounts of
carotenoids on a daily basis with no deleterious effects (old
world primates, herbivores, etc.).
9 . Other Carotenoids
In addition to β -carotene, of the other carotenoids, the most
information is available for α -carotene, lycopene, lutein, zeaxanthin,
and cryptoxanthin. To reiterate, these carotenoids
along with hundreds of others are the natural pigments in