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VI. Animal Factors in Hypomagnesemia
GRASS TETANY OF RUMINANTS
traction, and oxidative phosphorylation. Therefore, he believes that the
function of Mg probably extends to all of these enzymes.
In a review, Aikawa ( 1963, pp. 49-52) illustrated that in carbohydrate
metabolism, most of the enzymes along the glycolytic pathway to pyruvate require Mg at least in vitro. The initial oxidation of pyruvic acid requires Mg. In the tricarboxylic acid cycle, Mg is necessary for converting
a-ketoglutaric acid to succinic acid.
Aikawa also reported that, in lipid metabolism, transformation of pyruvic acid to acetyl-CoA and cholic acid to cholyl-CoA both are dependent
on Mg. He wrote that in vitro, the synthesis of DNA and RNA is inhibited by lack of Mg, and Mg activates all the enzymes that catalyze
the transfer of phosphate from ATP to a phosphate receptor or from a
phosphorylated compound to ADP. In vitro, many of these enzymes may
also be activated by Mn.
Wacker (1965) reported that the activity of the ATPases in vitro was
usually maximal when the concentrations of Mg and ATP were equimolar. Magnesium is known to form a 1 : 1 complex with ATP in the physiological pH range. This has been interpreted to indicate that either a Mg
ATP complex is the active substrate or that a Mg enzyme complex is the
active catalyst in phosphorylation.
Skou ( 1 965) proposed an enzyme system that functions in the active
transport of Na and K across cell membranes. The enzyme or enzymes
involved break down ATP by a two-step reaction. The first step requires
Na and Mg for maximum rate of transfer of the energy-rich phosphate
bond to a compound in the system. The second step is a dephosphorylation due to the effect of K. The optimum Mg-ATP ratio has been found
to be 2: I , for this enzyme system, when Mg, Na, and K are in the medium.
In a review article concerning tetany in cattle, Mershon indicated
(1964) that the four major cations of physiological importance (Na, K,
Ca, and Mg) play a role in nerve impulse transmission. He suggested the
physiologically maintained concentration gradient of K and N a propagates
the electrical potential at the membrane surface, and Ca and Mg stabilize the membrane. Further, the normal impulse transmission depends
on the antagonistic effects of Ca and Mg ions on the synthesis and release
of acetylcholine (ACH). At peripheral nerve endings ACH is formed,
stored, released, and hydrolyzed whenever a nerve impulse is transmitted. When Ca ions are relatively less depleted than Mg ions in tetany, the
rate of spontaneous ACH release increases. Tetany results, then, from
the increased irritability and spontaneous discharge of the sensory, motor,
and muscle fibers. Cells become more irritable as they more readily admit
Na ions or lose K ions. When the sum of Ca and Mg ions is reduced, the
GRUNES, P. R. STOUT, AND J. R. BROWNELL
integrity of the semipermeable membrane is lost, allowing the above
leakage. Mershon (1964) suggested the following unique biochemical
lesion of tetany : an electrolyte imbalance that permits spontaneous peripheral generation of nerve impulses. He presented a table recalculated
from Harbaugh and Dennis (1947) suggesting that Ca:K ratios are important factors in the physical response of the animal. He also implicated
low P levels, with tetany induced by a limiting of the ATP phosphorylation system, that is, a failure to maintain the last step in the energy-transfer system.
Underwood ( 1966) indicated that the hypomagnesemia that develops
in calves on milk diets, or on low-Mg rations or pastures, appears to be
a dietary deficiency of Mg. It develops gradually over a period of weeks,
and is accompanied by a fall in bone Mg to as low as 30-60% below normal. He also indicated that some of the slowly developing seasonal hypomagnesemia that develops in cows, as well as the tetany that occurs in
Norwegian cows maintained for long periods on rations of fodder cellulose, may also be attributed to a dietary deficiency of Mg, complicated
in the latter case by other factors such as undernutrition. He indicated
that the hypomagnesemia with tetany that arises suddenly in cows and
ewes turned out to spring grass cannot be considered a simple dietary
Mg deficiency because it is too rapid, it can occur on pastures or rations
of normal or even high Mg content, and it is not accompanied by any
gross fall in skeletal Mg. He emphasized, however, that several dietary
factors, including the level of Mg, exert a profound influence on the incidence of grass tetany.
C. TYPEOF ANIMALFEED
G. K. Davis (1965) stated that one of the peculiarities of the whole
picture of hypomagnesemic tetany has been that chemical analysis of the
forage has usually shown Mg to be adequate for nutritional requirements.
Why, then, is the Mg not available or utilized by the livestock? The problem is really one of Mg availability to the animal from the plant, and then
utilization within the animal after absorption from the intestinal tract.
Rook and Storry (1962) reported that ruminants on diets consisting mainly of roughage and succulent feeds absorbed only 5-30% of the Mg ingested. They presented evidence suggesting that Mg was less available
than average in young grass cut early in the season, especially if N and
K were high.
GRASS TETANY OF RUMINANTS
Considerable attention has been given to Mg availability as related to
the chemical composition of the feedstuff. Kemp ( I 958) showed hypomagnesemia and tetany in a field trial to be positively related to high rates
of K fertilization, with a superimposed (less drastic) effect from high N
fertilization. G . W. Butler and Metson ( 1967) compared forages from
tetany and nontetany pastures. They found that tetany pastures contained
lower Mg, Ca, Na, crude fiber, and possibly soluble carbohydrates, while
having higher concentrations of N and K. No generalization could be
made as to critical levels, however.
As indicated in Section V,D, Kemp et af. (1966) indicated that the concentration of higher fatty acids increased with the N concentration in the
forage. They also indicated that additions of higher fatty acids to winter
rations of cattle decreased the availability of Mg to the animals. Lomba
et af. ( 1968) and Paquay et af. ( 1968) conducted a comprehensive feeding
trial on 162 dairy cows and 55 dietary rations. They showed that.Mg absorption was enhanced by increasing Mg and Ca intake. However, N and,
to a lesser extent fat, gave higher fecal losses. They found no significant
correlation between K intake and the fate of dietary Mg.
It is often mentioned that Mg in the ruminant gut may be precipitated
as Mg ammonium phosphate and is therefore unavailable for absorption.
Phosphate-dependent precipitation of Mg in the ileal digesta of the ruminant calf has been demonstrated (Smith and McAllan, 1966). Further
experiments (Smith and McAllan, 1967) indicated that increasing the
NH, concentration increased the precipitation of Mg when phosphate,
but no Ca, was added. They concluded that precipitation of Mg with
phosphate would be appreciable only in the most distal portion of the
ileum where the pH is above about 6.5-7.0, and then only with fairly
high phosphate concentrations.
L’Estrange et al. (1967) found no association between serum Mg concentrations and high rates of N fertilization, the milk yield, or energy
intake of lactating ewes. The N fertilization more than tripled the estimated yield of herbage from April to July and increased the percentage
of nitrate N in the forage, but did not depress either the Mg or Ca concentration of the herbage. No clinical grass tetany developed, although
some of the ewes became hypomagnesemic, especially during the first
3 weeks of the experiment. The hypomagnesemia was independent of the
fertilizer treatment. Serum Ca concentrations (with one exception) remained normal throughout the trial and also were not affected by the N
D. L. GRUNES, P. R. STOUT, A N D I. R. BROWNELL
As indicated in Section V,F, Burt and Thomas (1961) showed that
adding sodium citrate to the diet of Ayrshire heifers for 8 weeks reduced
serum Mg below values obtained for cattle on a diet containing NaCI.
The level of Na was the same in both diets. Hirst and Ramstad (1957)
reported citric acid levels of 0.4-0.7% in fresh perennial ryegrass. Jones
and Barnes ( 1 967) reported a significant positive correlation between concentrations of nonvolatile organic acids in grasses and “preference rankings” (a visual estimation of animal grazing preference). The inference
was that animals tended to select those grasses with higher organic acid
concentrations. However, a higher correlation was found between “preference ranking” and total water-soluble dry matter.
Burau and Stout ( 1965) and Stout et al. ( 1 967) reported on trans-aconitate in range forage species. Forty-seven percent of the grasses studied,
and 17% of the nongrass species studied, contained higher than 1 % transaconitate. They suggested that aconitate and citrate could chelate Ca and
Mg, and might thus affect the normal transference pathways of Ca and
Mg within the animal. J . F. Hodgson (U. S. Plant, Soil and Nutrition
Laboratory, Ithaca, New York, unpublished data) found that citric acid
complexed Ca more strongly than did trans-aconitic acid. As indicated
in Section lll,C, Bohman et al. (1969) induced visible symptoms of grass
tetany in cattle by oral administration of KCI and either trans-aconitic
acid or citric acid. It was also mentioned that Scotto et al. ( 1 969) found
that adding KCI and citric acid increased the level of citrate in blood
plasma of cattle. High levels of citrate or aconitate in blood may be complexing Mg, and thus rendering the Mg less available to animals.
Camp et al. (1968) dosed sheep with K trans-aconitate and trunsaconitic acid. They then assayed serum samples for pyruvic acid, lactic
acid, citric acid, Na, K, Ca, Mg, P, globulin, albumin, total protein, and
urea-N. The most significant changes observed were an increase in organic P and progressive decrease in serum Mg. The trans-aconitic ion
was toxic to sheep; however, the mode of action of this substance could
not be attributed to any specific biochemical constituent assayed in that
investigation. They indicated that it was not possible to conclude that
trans-aconitate is the most common or essential etiologic factor for all
forms of the entire grass tetany complex.
Kennedy ( 1 968) indicated that sheep fed trans-aconitate maintained
normal levels of blood citrate, ketones, and aconitate, but showed large
increases in urinary citrate. The aconitate additions did not substantially
change the concentration of Mg and Ca in blood plasma and serum. Intravenously injected Na trans-aconitate increased citrate concentrations
GRASS TETANY OF RUMINANTS
in blood and urine. Plasma Ca and Mg concentrations were not depressed
by intravenous trans-aconitate administration, but urinary Ca excretion
increased and urinary Mg decreased.
ANI M AL
Underwood ( 1966) stated that evidence from Norway and New Zealand indicates that the energy balance of the animal is a further complicating factor in hypomagnesemic tetany. The utilization of Mg is decreased in animals on low-energy rations. This raises the dietary requirement for Mg, and makes it more difficult to maintain serum Mg values.
A N D PREGNANCY
Underwood ( 1966) stated: “Hypomagnesaemic tetany is most common
in older milking cows in the first 10 weeks after calving, although it can
occur at any stage of lactation in animals of any age, including suckling
calves 3 to 6 months old. All European breeds of cattle, whether dairy
or beef breeds, are susceptible and the disease is not restricted to females.
In ewes the highest incidence occurs in those with twin lambs, during the
first month after parturition.”
Hjerpe (1964) indicated that during a major outbreak in California in
which 4000-6000 head were lost, generally only pregnant and lactating
female cattle were affected. However, there was one confirmed case of a
bull with grass tetany, and 12-15 cases of tetany in steers. The disease
appears to be secondarily sex-linked, being related to Mg demands for
lactation and pregnancy. Thomas ( 1 965) concluded that the most likely
mechanism causing grass tetany is a decrease in Mg intake (from low Mg
concentrations in the feed) and/or low forage intake coupled with comparatively high Mg requirements. He believes that the tetany manifestation probably results from ionic imbalances within body tissues that influence the enzymatic activity of ion transport mechanisms and muscle
Blaxter and McGill ( 1956) presented a table (Table VI) calculated from
the data of other British workers. The greatest incidence of hypomagnesemic tetany occurred in cows which had had their third or fourth calf.
However, one needs to consider the age structure of the herds. In the last
column of Table VI, it can be seen that animals which had had six calves
were 15.2 times as susceptible to tetany as those which had had only one
calf. No breed differences were apparent, and both beef cows and dairy
cows were affected. In West Virginia, Horvath (1959) indicated that grass
tetany generally occurred in beef and dairy cows that had calved I to 3
D. L. GRUNES, P. R. STOUT, AND J. R. BROWNELL
TABLE V I
Effect of Number of Lactations on the Susceptibility
of Cows to Grass Tetany"
(% of total calved cows)
More than 6
(1st lactation = 1)
From Blaxter and McGill (1956).
weeks previously. The tetany generally occurred the second time they
had calved and often the fourth or fifth.
Hjerpe ( 1 967) considered hypomagnesemia to occur when Mg absorption from intake was exceeded by Mg losses in milk, feces, and urine.
As already stated (Section III,C) when the serum Mg level falls below
the renal threshold, Mg losses in urine fall essentially to zero. He presented a diagram showing total Mg storage in an animal and indicating
relative losses through feces, lactation, and urine.
Allcroft and Burns (1968) suggested that hormonal effects may be
involved in grass tetany. The increased incidence of grass tetany during
cold, wet, windy weather may be associated with changes in thyroid activity. Thyroid, parathyroid, and adrenal hormones may have regulatory
effects on absorption of Mg from alimentary tract, and on plasma Mg
concentration (Care et al., 1967).
Wilson (1964) suggested that a controlling factor may be wide variations in the amount of secretion of endogenous Mg into the digestive
juices. He speculated that spring herbage may have some pharmacologically active component that would cause an increase in the endogenous
excretion of Mg. He reported that aldosterone has been found to inhibit
the uptake of Mg by cells of the small intestine, and that aldosterone production was increased in response to high-K and low-Na intake. Therefore,
a high-K, low-Na ratio would tend to decrease Mg uptake. R. Allcroft and
GRASS TETANY OF RUMINANTS
Burns (1968) and Dobson et al. (1966) indicated that secretion of aldosterone by the adrenal gland may decrease the availability of dietary Mg.
However, Dobson et al. ( 1 966) suggested that increased secretion of
aldosterone probably has only a minor role in the production of hypomagnesemia.
R. Allcroft and Burns (1968) indicated that the onset of estrus can precipitate clinical symptoms in cattle in which some degree of hypomagnesemia is already present. However, the influence of steroid hormones
on the metabolism of Mg and Ca is not yet known.
I N STUDIES
Care et al. ( 1967) studied the effects of Na, K energy, and of bacterial
activity on the absorption of Mg from the mid-ileum of sheep. Absorption
of asMg from the gastrointestinal tract was much less on a diet of mowed
spring grass than on hay. This was not merely the consequence of bound
Mg in spring grass. The Mg concentration of the supernatant liquid from
duodenal digesta (obtained by centrifuging at 30,000 g for one-half hour)
was 16% higher with grass diet than with hay. Bound Mg, then, was meant
to be the Mg that was removed by centrifuging at 30,000 g. Magnesium
determined in the supernatant would include ionic as well as that chelated
and that in the form of ion pairs, such as that associated with sulfate or
phosphate, but still essentially in the solution.
Factors that may affect the absorption of Mg from the mid-ileum were
studied in conscious sheep with a Thiry-Vella loop. Magnesium absorption increased with either Na concentration or osmotic pressure within
the loop, but decreased with an increase in K concentrations. To test the
theory that bacterial absorption of Mg reduced the amount available for
absorption by the sheep, chloramphenicol was administered orally, greatly reducing the bacterial population in the mid-ileum, but this did not prevent acute hypomagnesemia.
Kemp (1958) followed serum Mg levels in 16 animals throughout the
tetany season. At any given time, the levels in the group varied over a
considerable range. This variation was greatest when the group mean was
somewhere in the midrange, 16-20 ppm of Mg. The variability decreased
as the group mean either increased or decreased from this point. He also
stated that “it was quite obvious, however, that there were individual
differences between the serum Mg contents, and some interesting information comes to light when these contents are studied over an entire
D . L. GRUNES, P. R. STOUT, A N D J . R. BROWNELL
year, for instance, in the case of a number of individual animals. It is then
found that serum Mg contents of 2 animals over an entire season rise and
fall fairly simultaneously but on a different level.”
In California, Stout, Brownell, and co-workers have used this observation to select animals for field tetany research, selecting animals from the
low portion of an entire herd. However, even within a group selected in
this manner, individuals were found to differ and to have very consistently
followed this same pattern. That is, the animal that was high at any given
time was likely to be found high at any other sampling time. This is based
on four groups of four animals sampled 28 times during the tetany season.
Independent of the supplemental feed treatment, animals within groups
maintained relative rank based on serum Mg level.
Kemp et al. (1961), summarizing several experiments, stated “that all
cows with serum Mg levels ranging from .5 to 1.8 mg./ 100 ml. (5- 18 ppm)
showed very low percentages of Mg not excreted in the feces (7-14%).
Other cows in the same experiments, receiving the same herbage, showed
normal serum Mg concentrations ranging from 2. I to 2.75 mg./ 100 ml.
(2 I to 27.5 ppm) and higher percentages of Mg not excreted in the feces
( 1 1-23%).” This is in agreement with the general assumption that some
cows are more susceptible to hypomagnesemia than others, although
differences in Mg intake and bone mobilization may play a role and were
not evaluated in the experiments summarized here.
G. W.Butler and Metson (1967) stated that the most consistent blood
chemical abnormality associated with grass staggers (grass tetany) was
low blood Mg. The fact remains, however, that low Mg levels are also
quite common in unaffected cows. It may be that much of the individual
variation in blood Mg level is genetically inherited, and that selected
breeding might reduce proneness to grass tetany. In a trial comparing
identical twin lactating cows, it was not possible to incriminate a particular nervous or hormonal mechanism to explain the variation in blood Mg
levels. The sudden failure or inadequacy of the regulatory mechanism involving Mg, or the significant effect of the negative energy balance on Mg
requirements, could not be explained in physiological or biochemical
terms. However, Care et al. ( 1 967) have suggested that much of the wide
individual variation in the reaction of different animals to the factors
causing hypomagnesemia may be ascribed to endocrine influences.
Smith ( I 963), in studying Mg absorption by milk-fed calves, considered
intestinal transit time to explain the variations in efficiency of Mg absorption. The regression line of absorption against transit time through the
distal ileum showed a mean increase of 8.5% Mg intake for each extra
hour of transit time.
GRASS TETANY OF RUMINANTS
VII. Treatment of Affected Animals
A detailed discussion of treatment of affected animals is presented by
R. Allcroft and Burns ( 1 968). The usual treatments involve administration of Mg and Ca compounds. If the convulsions and tetany are severe,
sedatives may also be administered. In the United States, commercial
solutions often used for intravenous injections contain Ca and Mg gluconate with added dextrose and phosphate. R. Allcroft and Burns ( 1968)
indicated that intravenous hiections should be given slowly, and the response watched carefully, because of the danger of death from cardiac
arrest. They mentioned that Mg lactate is considered safer than Mg sulfate, but even so must be administered with care. They stated that intravenous Ca injections are sometimes combined with subcutaneous Mg
Unless the animal is removed from the tetany-producing pasture and
fed hay and concentrates, the blood Mg level is likely to become dangerously low 24-37 hours after the intravenous or subcutaneous injection.
R. Allcroft and Burns ( 1 968) suggested that follow-up treatment should
consist of daily oral administration of about 30 g of Mg (2 oz calcined
magnesite, containing 85% MgO). After a week, the oral dose can be
gradually reduced. They indicated that absorption of Mg by animals has
been shown to be better from the oxide than from sulfate or carbonate.
VIII. Prevention of Grass Tetany
As was discussed in Section IV, Mg fertilization is recommended for
good plant growth when the exchangeable Mg is less than 10% of the
cation exchange capacity of the soil, or less than 100 Ib of exchangeable Mg per acre. The latter figure is about 0.41 meq per 100 g of soil,
or 5.0 mg of Mg per 100 g of soil. When cattle are grazed on pastures,
higher values for soil Mg are advisable. For grazing animals in West
Virginia, it has been recommended (Horvath and Todd, 1968) that soil
Mg equal at least twice the percent saturation of K , and that the Ca:Mg
ratio not be higher than 5 : 1.
There has been appreciable research relating Mg fertilization to concentrations of Mg necessary for good plant growth. Magnesium deficiency
symptoms of plants frequently occur at 0.05-0.10% Mg, although some
higher values for Mg-deficient plants are also found in the literature (Embleton, 1966). However, as discussed earlier, cattle require Mg concentrations of 0.20% Mg or more in the forage.
D. L. GRUNES, P. R. STOUT, AND .I. R. BROWNELL
The effect of fertilization on content of rye forage grown on coarsetextured soil is indicated in Table IV, which is adapted from Lowrey
and Grunes ( 1968). Although K fertilization decreased the concentrations
of Mg in the plants, the addition of Mg with the K did increase the concentrations of Mg. Potassium fertilization decreased the concentrations
of Ca in the plants, and the addition of both K and Mg decreased the Ca
concentrations still further. As expected, fertilization with K increased the
K concentrations in the plants. However, the further addition of Mg did
not consistently affect the K concentrations. The addition of K increased
the ratios of K/(Ca Mg). However, the further addition of Mg did not
change this ratio, since Ca concentrations were decreased.
The aforementioned rye forage was harvested at periodic intervals and
fed to milking Jersey cows. As indicated earlier, hypomagnesemic tetany
often occurs when Mg in the blood serum is 5-10 ppm. For those treatments which received no Mg fertilizer, the Mg in blood serum dropped
after the feeding of rye forage was initiated, but rose again later in the
season (Lowrey and Grunes, 1968). However, in no case did the Mg in
the blood drop below 18 ppm of Mg in the blood serum. [Rook and Storry
( 1962) have reported a temporary decrease in Mg concentrations in the
blood of dairy cattle during spring grazing.] The serum Mg level did not
drop for the cattle fed Mg-fertilized forage (Lowery and Grunes, 1968).
The concentration of Mg in the urine dropped rapidly for those cattle
fed rye forage grown on land not fertilized with Mg (Lowrey and Grunes,
1968). In fact, the level approached the concentration of 5- I0 ppm of Mg,
which Rook and Balch (1958) indicated was typical of animals suffering
from grass tetany. The Mg in the urine did not decrease below 50 ppm of
Mg for animals fed the rye forage from the Mg-fertilized area (Lowrey and
Wolton ( I 963) reviewed the effect of Mg fertilization on Mg concentrations in forage. She indicated that, in the British Isles, high rates of
Mg (365 and 1620 kg of Mg per hectare) have consistently increased
herbage Mg to levels above 0.2% and have prevented hypomagnesemia,
sometimes for a number of years. She indicated that low rates (68 kg/ha
or less) of applied Mg have often been ineffective in increasing herbage
Mg. Low and medium rates of Mg fertilization were most effective on
coarse-textured soils of low base-exchange capacity, and on soils with
a low Ca content.
She stated that calcined magnesite, Kieserite, and Epsom salts were
more effective sources of Mg than dolomite for grassland, especially on
soils with a high Ca content. (Calcined magnesite is Mg carbonate heated
to a high temperature, resulting in MgO. It contains about 50% Mg.