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Nitrate Toxicity and Sodium Deficiency Associated
with Hypomagnesemia, Hypocalcemia and the Grass
Tetany Syndrome in Herbivores
T.W. Swerczek, DVM, PhD.
The factors inducing the grass tetany syndrome
have been a mystery to scientists since the
syndrome was first described in 1930. It is
hypothesized that important factors for the
pathogenesis of the grass tetany syndrome are
nitrate toxicity and a dietary sodium deficiency
which induces an electrolyte and mineral imbalance.
The grass tetany syndrome is associated with
a deficiency of magnesium (hypomagnesemia),
and a coexisting calcium deficiency (hypocalcemia),
and sodium deficiency (hyponatremia) and an
excess of potassium (hyperkalemia) in the blood
of affected animals.
Grass tetany affects cattle and other herbivores
that are high producing and being fed a ration
excessive in protein which includes non-protein
nitrogenous compounds. A common factor is excessive
nitrogen fertilization of pastures. Yet, the mechanism
of action by which excessive nitrogen or nitrogenous
compounds predispose cattle to grass tetany has
not been adequately investigated. The following
discussion will disclose the current important
scientific literature and the author's clinical
and pathological experience with the grass tetany
syndrome in herbivores. During the last decade
the unprecedented late frosts and freezes to lush
pasture forages provided important clues to the
current knowledge on the grass tetany syndrome
as well as other disorders associated with nitrate
toxicity in ruminant and non-ruminant herbivores.
In
1930, the original scientific report on the
pathogenesis of grass tetany, Sjollema states that
grass staggers (tetany) occurs most frequently
during springs when there is a superabundance of
young, rank, quick-growing grasses rich in proteins.
He also notes that it occurs during the winter
when feed is excessive in protein. In some herds,
cattle manifest pica suggesting that some necessary
ingredient is lacking in the fodder. He also observed
animals grazing in strongly manured pastures stripped
all trees within their reach of herbage until they
were barren. Interestingly, he also found that
the sodium-content in the blood was subject to
fluctuations, probably greater than in normal animals.
8 It is likely that the pica the cattle were experiencing
was due to a sodium deficiency.
There has been very
little progress in the understanding of the factors
responsible for the syndrome since the original
report by Sjollema.8 However, he and other early
workers did observe some very important clues that
were later confirmed by other workers, but these
clues have not been appreciated until recently.
He observed that high nitrogenous diets and an
unknown factor, which was later identified as sodium
by other workers, are important in the pathogenesis
of hypomagnesemia and hypocalcemia in cattle.
In
1954 Smith and Aines experimentally deprived
sodium from dairy cows and induced clinical signs
of grass tetany. 9 This landmark research was confirmed
by other workers. Paterson and Crichton found
that low concentrations of sodium were found in
tetany-prone grass, and they prevented grass tetany
by supplementing cows with sodium chloride. 7 In
a field study, Butler observed an increased incidence
of grass tetany at low sodium concentrations in
the grass and the incidence of grass tetany disappeared
at sodium concentrations above 0.2% in the grass.
3
Unfortunately, this early work on the importance
of adequate sodium has been either overlooked
or ignored, as the majority of mineral supplements
currently used in an attempt to prevent grass
tetany are deficient in sodium and excessive
in magnesium. This is causing weight loss, wasting,
severe diarrhea, and reduced milk production
when fed with high protein rations. The consequence
of excessive magnesium supplementation was reported
by Urdas, et. al. They reported on the importance
of appropriate amounts of magnesium in rations
for dairy cows, especially in rations high in
protein, as excessive magnesium had drastic adverse
effects on milk production and other clinical
signs, including diarrhea. 14
The clinical signs
of grass tetany or hypomagnesemia are unlikely
to occur unless there is also a hypocalcemia.
In many cases the clinical signs of grass tetany
and milk fever are similar, and probably the triggering
mechanisms or factors inducing the syndromes
are similar. The clinical signs are usually seen
in animals in full lactation and high producing
cows. The increase in feed and forage intake, even
with adequate magnesium and calcium, may only partially
compensate for loss of magnesium and calcium
in the milk. Without exception, most researchers
have observed that clinical signs of grass tetany
rarely occur unless affected animals are high producing
and being fed a ration high, or excessive in
protein which includes non-protein nitrogenous
compounds. 2
Most researchers agree that a common factor associated
with grass tetany is excessive nitrogen fertilization
of pastures. 1 Yet, very few have investigated
why excessive nitrogen, or nitrogenous compounds
predispose cattle to grass tetany. Martens and
Schweigel summarized work on excessive nitrogen
as it relates to grass tetany. These studies suggest
that excessive NH4+ may interfere with the absorption
of magnesium from the gut, but did not offer any
other explanation. 6 However, their research shows
that the lack of sodium and excessive potassium
seemingly also interferes with the absorption of
magnesium from the gut. 5,6
Since the first report
and all subsequent research on the pathogenesis
of grass tetany in cattle, excess nitrogen was
suggested as the primary initiating factor for
inducing hypomagnesemia and hypocalcemia. Yet,
the factor associated with excessive nitrogen
has not been identified. It is hypothesized that
the nitrogen factor is related to the nitrate anion.
The subsequent discussion will outline the observations
and findings that suggest that excessive nitrate
is involved in the pathogenesis of hypomagnesemia,
hypocalcemia, hyponatremia and hyperkalemia,
all of which are involved in the grass tetany syndrome
in cattle and other herbivores.
Several researchers
report that hypomagnesemia may occur in animals
foraging on diets low in magnesium, but it may
also occur when diets have adequate magnesium in
the forages or rations. This suggests that there
is some factor(s) that is either tying up the magnesium
and/or chelating the magnesium making it unavailable,
or causing it to be removed from the body excessively
through the kidneys, mammary glands and in the
feces, thus causing an acute hypomagnesemia. This
was suggested by Grunes, et. al. after demonstrating
that fertilization with high nitrogen appreciably
increased the nitrogen in plants, thus increasing
their potential for causing grass tetany. In addition,
they found that fertilization with broiler litter
markedly increased the potassium and magnesium
concentrations, as well as the ratio of K/ (Ca+Mg),
which would make the forage more likely to produce
grass tetany. They also found that there was an
increase in organic acids and suggested that these
anionic organic acids may be chelating with magnesium
and calcium creating a hypomagnesemia and hypocalcemia
when forages were high in organic acids. 4 Organic
acids are more likely to be excessively high in
diets high in carbohydrates, but when the diets
are high in protein and non-protein nitrogenous
compounds, the anionic ions likely to be excessive
are related to nitrate.
Numerous researchers have
found that grass tetany occurs most often in older
brood cows grazing lush growth of pastures in early
spring, and the triggering of the grass tetany
syndrome includes environmental conditions of cool,
cloudy and wet weather, promoting rapid, lush growth
of cool season grasses. These environmental conditions,
which also include frosts and freezes, will cause
acute spikes in potassium as well as nitrate in
affected growing pastures. Analyses of these affected
pastures during and after periods of frosts and
freezes revealed elevated levels of potassium and
nitrate. 11 Nitrate in the form of potassium nitrate
is reportedly the form which herbivores are exposed
to nitrate. During periods of stress to pastures
forages, the acute spike in potassium and nitrate
is seemingly causing an electrolyte and mineral
imbalance in affected herbivores. These imbalances,
in pastures forages include an increase in the
ratio of K/ Ca+Mg, and a deficiency in sodium.
These imbalances may not be readily apparent, unless
blood samples are obtained while animals are suffering
from marked clinical signs, as the body can obtain
cations from tissues until they are depleted, then
severe acute clinical signs and death occur.
Since
sodium aids in the prevention of hypomagnesemia
and hypocalcemia, and these syndromes are both
associated with high producing cows on high nitrogenous
rations, it was suspected that similar syndromes
are occurring in other herbivores including horses
where high nitrogenous diets are suspected of inducing
an immune suppression, reproductive losses and
other syndromes associated with a host of opportunistic
diseases, likely related to an increase in nitrate
in the diet. 11 Also, as with cattle, adequate
sodium in the diet seemingly aids in the prevention
of these syndromes. To test this hypothesis, horses
were given a high protein diet with and without
the addition of sodium in the diet and the levels
of nitrate in the blood were analyzed. Diets without
the addition of sodium chloride caused a marked
elevation of nitrate in the blood, whereas, the
supplementation of sodium chloride, sodium bicarbonate,
or zeolytes high in sodium, to the same high protein
ration returned the nitrate levels in the blood
to normal levels or levels seen in horses on low
protein diets, within 24 hours after the addition
of sodium to the diet. 12 These findings suggest
that sodium indeed is neutralizing the nitrate
in the blood, and/or gut by excreting the excessive nitrate that is exogenously in the diet, or the
nitrate that is endogenously produced by bacteria
in the gut. The excess nitrate is likely being
eliminated as an anionic complex associated with
sodium by the kidneys, in the feces, or in the
milk in lactating animals. The high nitrate in
the milk, associated with the feeding of high protein
diets in herbivores, may also affect suckling neonates
with the same detrimental effects as in adults.
This explains why neonates on dams that are fed
excessive proteins seemingly are affected with
a multitude of opportunistic gastrointestinal diseases,
including gastric ulcers and other intestinal disorders.
Conversely, dams fed a low protein diet and adequate
sodium, their neonates rarely suffer from these
gastrointestinal disorders.
When there is a deficiency
of calcium and sodium and excessive potassium and
nitrogen in the soil, there is likely a more dramatic
spike in potassium and nitrate in plants during
and after stress, like frosts and freezes, to pasture
forages. If the excessive potassium and nitrate
in affected forages is consumed by herbivores,
it may induce a toxicity and/or mineral and electrolyte
imbalances. Nitrate in the diet is utilized in
protein metabolism. However, if the nitrate is
excessive in ruminants, in some cases, nitrate
is converted to nitrite by the gut bacteria and
methemoglobinemia may occur. The majority of excessive
nitrate is eliminated through the gut and kidneys,
or mammary glands in lactating herbivores.
Since
cations utilized to eliminate the excessive nitrate
from the body have different solubilities and affinities
for nitrate, the body will utilize the cations,
if available in adequate concentrations that have
the highest affinity for nitrate. Magnesium, calcium
and then sodium are the most soluble and potassium
the least soluble 13, and likely the affinity of
each cation for nitrate is similar to their solubility
with nitrate. It is hypothesized that if there
is a deficiency of sodium, and most forages and
rations are deficient in sodium and excessive in
potassium, and when there is a spike in nitrate,
or excessive nitrate in the body, anionic nitrate
is eliminated from the body as an ionic complex
associated with magnesium and calcium. If nitrate
is excessive, a hypomagnesia and/or hypocalcaemia
may develop as the body is eliminating magnesium
and calcium with the excessive anionic nitrate.
However, if there is adequate sodium in the diet
and organs and tissues, the excessive anionic nitrate
is removed by the gut, kidneys, and mammary glands
in lactating animals, as an ionic complex associated
with sodium, and magnesium and calcium are maintained
at physiologic levels and hypomagnesia and/ or
hypocalcaemia will not occur. For this reason adequate
levels of sodium in the body and ration will lessen
or prevent the drastic effects of nitrate toxicity.
Also, it explains why adequate sodium in the diet
will aid in the prevention of grass tetany, which
is associated with high potassium and low magnesium
levels. It also explains why the grass tetany syndrome
cannot be readily induced experimentally unless
cattle are exposed to high nitrogen or nitrate
forages, and likely low sodium diets.
Most cattlemen
assume they have adequate sodium if cattle are
exposed to salt blocks. Cattle and other herbivores
cannot obtain enough salt or sodium from hard salt
blocks during periods of acute needs. The most
dominate animals in a herd will horde a salt block
and the remainder will leave without any salt.
Even the animals that horde the block cannot consume
enough salt to neutralize the acute excessive dietary
nitrate during periods of acute stress to forages,
like frosts and freezes to high nitrogenous forages.
Therefore, it is imperative to either have adequate
sodium in the complete rations, which is preferable,
and/ or to have readily available sodium in the
form of sodium chloride, and/or sodium bicarbonate
in the loose form always available, especially
in times when environmental conditions are conducive
for nitrate spikes in forages. Seemingly, the excessive
potassium in forages, which occurs along with the
excessive nitrate after a frost and freeze, discourages
animals to consume salt, or sodium compounds free
choice as potassium substitutes for sodium in plants
as well as in animals. This further increases the
ratio of K/Ca+Mg and for this reason sodium needs
to be force fed in complete rations for optimum
results. It is important to have fresh water available
and place salt mixtures near water sources.
The
livestock industry has limited sodium chloride
in mineral supplements to encourage livestock to
consume more minerals, and this has led to the
over consumption of essential minerals that are
normally not toxic if fed at correct levels, but
can be toxic if fed in excessive amounts. The restriction
of sodium is seemingly contributing to a multitude
of syndromes, including hypomagnesemia, hypocalcemia
and the downer cow syndrome as well as a host of
opportunistic diseases. Also, the restriction of
sodium and the prolonged over feeding of magnesium
may result in decreased performance, especially
milk production in dairy cows and severe reduction
of calf weights in calves on beef cows. Furthermore,
the forced feeding and overfeeding minerals that
are contaminated with heavy metals have drastic
effects on performance due to toxicities, mineral
imbalances, immune suppression, and the induction
of a host of opportunistic diseases. It is important
to have adequate, pure forms of calcium and magnesium
of high quality in the diet for high producing
animals. Most diets have adequate calcium and magnesium,
but when there are acute spikes in anionic ions,
the calcium and magnesium may be acutely depleted,
resulting in hypocalcemia, hypomagnesemia and a
hyponatremia. But, adequate access to sodium appears
to help alleviate these acute deficiencies during
spikes in nitrate.
It is not an uncommon practice
for some cattlemen to either intentionally or unintentionally
allow cattle to go without salt. The practice is
sometimes used to allow the easily gathering of
cattle that are salt starved. If there is a spike
in potassium and nitrate due to adverse environmental
conditions while cattle are deprived of salt, cattle
are often found dead, or suffering from a host
of metabolic and opportunistic diseases. Seemingly,
cattlemen with the healthiest cattle are very aware
of the need for cattle to have unlimited access
to loose salt and/ or loose trace mineralized salt
at all times. These same cattlemen have observed
that if cattle are without salt, even for short
periods of time, some may be found dead, or suffering
from clinical signs of grass tetany, especially
after periods of severe environmental stress, like frosts or freezes to lush
pastures containing legumes. 10
According to the scientific literature, nitrate
is relatively non toxic, unless the excessive nitrate
is converted to nitrite by bacteria in the gastrointestinal
tract. This may lead to methemoglobinemia and anoxia in affected animals. However,
another form of nitrate toxicity that is likely more common and more detrimental,
and previously overlooked may occur when the nitrate depletes essential cations
in an attempt to maintain critical ionic balances. The excessive nitrate anions
are excreted along with cations to maintain a critical ionic balance. This may
result in mineral and electrolyte imbalances that may initiate a host of metabolic
diseases in ruminants, as well as monogastric animals, including horses. This
explains why cattle and other ruminants and horses appear to be suffering from
a host of metabolic disorders when exposed to forages and diets high in protein,
non-protein nitrogenous compounds and nitrate. The nitrate anion per se may not
be that toxic in cattle and horses, but indirectly it appears to be inducing
mineral, electrolyte and ionic imbalances, and secondary immune suppression associated
with these disorders. Sodium chloride, sodium bicarbonate, and high sodium zeolite
compounds appear to neutralize the toxic effects of excessive nitrogenous diets,
including nitrate toxicity.
Nitrate toxicity is difficult to evaluate and
it is imperative to consider nitrate levels in
forages and well as in the blood and biological
fluids of affected animals. Nitrate levels in the
blood are difficult to interpret as both the amount
and the duration of exposure need to be considered.
The excessive nitrate in the blood is eliminated
by excretion with essential cations, thus giving
the false impression that nitrate toxicity did
not occur as the nitrate level in the blood may
appear to be too low to be significant. However,
the excessive nitrate may have been previously
excreted along with essential cations inducing
imbalances which are manifested clinically as hypocalcemia,
hypomagnesemia, hyponatremia, and often a hyperkalemia.
Nitrate toxicity, that may have induced these disorders,
may not be apparent when blood or biological fluids are analyzed. Also, nitrate
toxicity may be overlooked by only analyzing forages for nitrate levels. The
over feeding of protein and non-protein nitrogenous compounds may lead to nitrate
toxicity by the endogenous production of nitrate by the bacteria of the gut.
This too may induce mineral and electrolyte imbalances, and a host of opportunistic
diseases that have been confusing to the livestock industry because the primary
cause, nitrate toxicity is not apparent and overlooked.
Cattle and horses with
apparent nitrate toxicity, and cattle with clinical
signs of grass tetany, will have elevated levels
of aldosterone suggesting a sodium deficiency,
yet the blood levels of sodium may be in the low
normal range, suggesting that a sodium deficiency
is not present, but it drops below normal levels
shortly before death. Unless blood samples are
obtained shortly before death, the severe sodium
deficiency may not be apparent. Aldosterone is
a steroid hormone belonging to the mineralocorticoid
family that is produced by the adrenal gland and
acts to conserve sodium and secrete potassium,
and increase blood pressure. The elevated aldosterone
indicates that the system is attempting to conserve
sodium, which is deficient, and substituting potassium,
which is excessive, for sodium. While the system
is sparing sodium, likely calcium and magnesium
is being utilized to eliminate the excessive nitrate,
thus creating hypomagnesemia and hypocalcemia.
Therefore, aldosterone levels may be the best indicator
of ionic imbalances induced by the excessive nitrate
anion.
In summary, hypomagnesemia and hypocalcemia
are more likely to occur in high producing animals
that are fed diets high or excessive in protein,
and non-protein nitrogenous compounds, including
nitrate. When these components of the diets are
high, anionic imbalances due to nitrate occur in
forages as exogenous sources, but they are further
produced endogenously by the bacteria of the gut
of affected animals. When this occurs, the excessive
anionic ions need to be neutralized by cations
and this causes a "washing out" effect
of essential cations including calcium, magnesium
and sodium in the urine, feces and milk, and then
hypocalcemia, hypomagnesemia and hyponatremia occur. Even when these cations
are at recommended levels in the diet, they may not be adequate and become acutely
depleted during periods of environmental stresses. A simple prophylaxis is not
to over feed protein to herbivores, but this is not always practical when producers
are striving for maximum production. When there are severe environmental stresses
like frosts and freezes to lush forages, especially forages containing legumes,
cationic and anionic imbalances in affected forages are further exacerbated.
However, the over feeding of protein can be somewhat alleviated by feeding adequate
calcium, magnesium and sodium preferably in complete rations, but also they should
be available free choice if affected animals desire and need more to neutralize
the anionic excesses. Calcium and sodium if fed at optimum concentrations are
non toxic, but magnesium if fed at high levels for prolonged periods, may be
toxic and may result in chronic wasting, reduced milk production and diarrhea.
Seemingly, the feeding of adequate levels of magnesium and increased levels of
calcium and sodium during period of environmental stress will aid in the prevention
of grass tetany that is induced by acute anionic imbalances due to nitrate in
high producing animals.
It is apparent that nitrate toxicity in herbivores
is much more prevalent than previously reported.
A well documented form of nitrate toxicity occurs
in ruminants when nitrate is converted to nitrite
by the microflora of the gastrointestinal tract
and then the nitrite induces a methemoglobinemia
and anoxia. However, it is hypothesized that
a much more common mode of nitrate toxicity, and
previously not recognized, is when nitrate toxicity
induces a severe electrolyte and mineral imbalance
in ruminant and non-ruminant herbivores. This
form of nitrate toxicity is an important factor
in the pathogenesis of the grass tetany syndrome
and likely other syndromes in herbivores, including
reproductive disorders in all herbivores, including
horses. Seemingly, adequate dietary sodium not
only protects against nitrate toxicity, but also
aids in the prevention of the grass tetany syndrome
in herbivores, and other metabolic and reproductive disorders induced by nitrate
in herbivores.
References:
1. Bartlett, S. et. al.: The Influence of Fertilizer
Treatment of Grassland on the Incidence of
Hypomagnesaemia in Milking Cows. Brit. Vet.
J. (1954)110:3-19.
2. Burns, K.N. and Allcroft, R.: Hypomagnesaemia Tetany in Cattle. I. Incidence,
aetiology, diagnosis and treatment. Br. Vet. J. (1967)123.340-347.
3. Butler, E.J.: The Mineral Element Content of Spring Pasture in Relation
to the Occurrence of Grass Tetany and Hypomagnesaemia in Dairy Cows. J. Agric
Soc (1963)60:329.
4. Grunes, D.L. et.al.: Effect of Broiler Litter and Nitrogen Fertilizer
on the Grass Tetany Potential of Tall Fescue. 1974, Agron. Abstr. Am. Soc.
Agron., Madison, Wisconsin. p. 139.
5. Martens, H.: Outstanding Salt Article. Beef Magazine, August, 2003
6. Martens, H. and Schweigel, M.: Pathophysiology of Grass Tetany and Other
Hypomagnesemias. In Veterinary Clinics of North America: Food Animal Practice.
Vol 16, No. 2, July 2000.pp 339-368.
7. Paterson, R. and Crichton C.H: Grass Staggers in Large Scale Dairying
on Grass. Journal of the British Grassland Society (1960)15:100.
8. Sjollema, B.: On the Nature and Therapy of Grass Staggers. The Veterinary
Record.(1930), Vol 10, pp. 425-430.
9. Smith, S.E. and Aines, P.D.: 1. Bartlett, S. et. al.: 1954. The Influence
of Fertilizer Treatment of Grassland on the Incidence of Hypomagnesaemia
in Milking Cows. Brit. Vet. J. 110:3-19.
10. Swerczek, T.W.: Don't Short Salt. Beef Magazine, June, 2003. P.14
11. Swerczek, T.W. et. al.: Mare Reproductive Loss Syndrome: A Forage Induced
Electrolyte and Mineral Imbalance. Kentucky Association Equine Practitioners,
Emerging Disease Seminar. March 7, 2002. Lexington, KY.
12. Layton, G.E. and Swerczek, T.W.: Effect of Sodium on Endogenous Nitrate
in Horses Fed a High Protein Diet. 2007, Unpublished data.
13. Weast, R.C.: Editor, Handbook of Chemistry and Physics. 52nd edition.
The Chemical Rubber Co. 18901 Cranwood Parkway, Cleveland, Ohio. 44128.
14. Urdaz, J.H. et. al. Importance of Appropriate Amounts of Magnesium in
Rations for Dairy Cows. Vet Med Today, Timely Topics in Nutrition. JAVMA,
222. No. 11, June 1, 2003, 1518-1523.
This paper was presented at the Annual Growers Mineral Solutions meeting,
Milan, Ohio, December, 4, 2007. Dr. Swerczek's address is 664 Providence
Road, Lexington, KY. 40502
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