Page 513 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

480 SECTION | V Metals and Micronutrients

VetBooks.ir including frozen water sources, unpalatable water sources, Once the hypernatremia situation is corrected, the idio-
genic osmoles will take 48 72 h to decrease back to nor-
mechanical failure, overcrowding or naive animals, and
mal levels. As in the acute situation, a rapid decrease in
owner neglect.
serum sodium will develop an osmotic gradient causing
water to move into the brain with resulting cerebral
PHARMACOKINETICS edema and the development of clinical signs.
AND MECHANISM OF ACTION
TOXICITY
An increase in sodium intake leads to a rise in sodium
concentration in the serum and a rapid distribution In all situations involving salt intake, the intake of water
throughout the body. Osmolarity of the ECF is monitored will have great impact and must also be considered. The
by osmoreceptors in the hypothalamus and the body acute toxic dose of sodium chloride is approximately
reacts to increases by stimulating thirst for increased 2.2 g/kg in swine, equine and bovine species with the
water intake. Additionally, the release of antidiuretic hor- ovine toxic dose approximately 6 g/kg (Osweiler et al.,
mone from the posterior pituitary will cause increased 1985). Swine appear to be the most sensitive domestic
water retention by the kidneys. These responses should animal and involve the greatest number of clinical reports.
function to quickly restore normal osmolarity but may Both swine and poultry can be severely affected when
only be effective if the osmolar changes are gradual and water intake is greatly restricted or with high-salt diets
sufficient water is available to the animal. As the sodium and only moderate water restriction. Increased water
ion concentration of the serum increases, water will move requirements will increase the susceptibility of lactating
out of the interstitium and intracellular fluid into the ECF cows and sows to salt poisoning, making them more sen-
along the osmotic gradient. Sodium will passively diffuse sitive to sudden restrictions in water. The acute toxic
across the blood brain barrier increasing the sodium con- dose of sodium chloride in dogs is given as 4 g/kg, but
centration of the cerebral spinal fluid above the normal clinical signs have been reported for lesser ingestions
range (135 150 mmol/L). During this developing hyper- (Barr et al., 2004) and an ingestion greater than this was
natremia, the cells of the brain will also increase their reported with only mild clinical signs. Cats and dogs can
intracellular osmolarity to prevent excess water loss to safely tolerate 3.7% salt in the diet if fresh water is con-
the ECF, which would cause cell shrinkage. If the tinuously available (NRC, 2005). Horses appear to be
hypernatremia develops too quickly and this protective rarely affected with classic salt poisoning but can
mechanism fails, significant cell shrinkage occurs and develop it with conditions of increased salt intake and
the entire brain shrinks and pulls away from the calvar- sudden water restriction. Horses are, however, subject to
ium resulting in the disruption of the blood supply to dehydration and electrolyte abnormalities especially
the brain. This can result in subarachnoid, subdural or under conditions of exercise and high ambient tempera-
intravascular hemorrhages (Hardy, 1989). In severe tures (Cohen et al., 1993).
cellular dehydration, the result can be seizure-like activ- Clinical signs have best been described in swine and
ity and death. If the increase in sodium concentration of include loss of appetite, thirst, restlessness, pruritus and
the brain cells continues, there will be an inhibition of constipation. These early clinical signs can progress over
glycolysis and a decrease in the energy available in the several days to aimless wandering, head pressing, circling
cell. While sodium will passively diffuse into the brain, or pivoting around a limb. The animal may display
it is an energy-requiring active process that transports seizure-like activity and assume a dog-sitting position,
sodium out. Thus the brain response to a rapid decrease draw its head back in a jerking motion and fall over on its
in serum sodium is delayed and the developing osmotic side (Osweiler et al., 1985; Niles, 2004). Terminally, the
gradient will cause water to move into the brain causing animal will be in lateral recumbency with paddling and
swelling, cerebral edema, and the development of clini- opisthotonus. Cattle with acute excess salt intake may
cal signs. develop gastroenteritis, weakness, dehydration, tremors,
Changes in cellular osmolarity will occur in both acute and ataxia. The cattle may appear to be blind and develop
and chronic hypernatremia situations, but changes to seizure-like activity or partial paralysis including knuck-
osmolarity on a chronic basis will involve the accumula- ling over at the fetlocks. Terminally, cattle can also be in
tion of more osmotically active organic compounds, lateral recumbency with paddling and opisthotonus. Cattle
termed idiogenic osmoles. These include taurine, myoino- can die within 24 h following the appearance of severe
sitol, glycerophosphoryl-choline, glutamate, glutamine, clinical signs. Recovered animals may drag the rear feet
betaine, and phosphocreatine. Maximum concentrations or knuckle over at the rear fetlock without exhibiting pain
of idiogenic osmoles occur within 48 72 h and can (Osweiler et al., 1985). Poultry and other birds may
account for 60% of the change in cellular osmolarity. exhibit clinical signs of depression, weakness, dyspnea