Grass Tetany by André Voisin

CHAPTER 13

Some physiological effects of magnesium deficiency

SUMMARY FOR NON-SPECIALIST READERS
A ration with a very low magnesium content fed to rats reduces the level of magnesium in the blood serum and gives rise to hyperexcitability, with the result that the least excitement produces convulsions.
Feeding young female rats on a ration moderately low in magnesium, but not giving rise to convulsions, nevertheless renders them susceptible to tetany in their subsequent lactation.
Triggering of the convulsions is followed by a sudden increase in the level of magnesium in the blood serum, which can make diagnosis difficult either in a single animal or in a herd. Despite this increase, however, the tendency towards convulsions remains.

General physiological effects of magnesium deficiency

At the beginning of this book it was stated that grass tetany was due to a disturbance in the metabolism of magnesium, one of the causes of which could be a deficiency of magnesium in the ration. In the present chapter the general physiological effects of true magnesium deficiency, that is, the effects of a low-magnesium diet, will be studied.
In the years between 1930 and 1940 many experiments 1 undertaken particularly with rats and dogs revealed the physiological consequences of a deficiency of magnesium, all the other elements in the diet remaining normal. The most important of these effects are the following:
  1. Growth retardation.
  2. Very considerable diminution in the magnesium 2 content of the blood serum without any necessary diminution in the latter's calcium content.3 In certain cases the phosphorus content of the blood serum is increased.
  3. The magnesium content of the red blood corpuscles (erythrocytes) drops a little less rapidly 4 than the magnesium content of the blood serum.
  4. The magnesium content of the tissues varies but little;5 but magnesium deficiency produces a considerable increase in the calcium content of the heart, 6 muscles and kidneys, the increase being most marked in the latter and rising as high as 500%.
  5. Considerable drop in the amount of magnesium excreted in the urine 7 with a less marked reduction in the amount excreted in the faeces.
  6. Vaso-dilation 8 of the peripheral blood vessels along with hyperaemia which is often of a transitory nature and disappears after a period.9
  7. Considerable rise in the cholesterol content of the blood plasma with a relatively even greater increase in the cholesterol esters.10 The fatty acid content of the plasma is reduced.
  8. Hyperexcitability, which makes a more rapid appearance, the lower the magnesium and the higher the calcium contents of the ration. Any noise 11 or excitement is enough to trigger off convulsions. Where the rations are very low in magnesium the animals generally die in the course of such a convulsion.
The present chapter will confine itself to such details of these manifestations as may aid our understanding of certain phenomena that occur in association with grass tetany.

Lactation makes magnesium-deficient rats susceptible to tetany

The lower the percentage of magnesium, the more rapidly convulsive attacks develop in animals being fed a low-magnesium ration.
Tetany convulsions make their appearance after 10-14 days in rats being fed a ration containing 1 mg.12 magnesium per 100 gm. If the ration contains 1 - 5 mg magnesium per 100 gm. convulsions appear only after 22 days, whereas with a content of 2 mg. the delay is 33 days. When the magnesium content of the ration is raised to 5 mg. per 100 gm. there may be some hyperexcitable animals to start with but by the time 3 weeks have elapsed they appear to have become completely resistant. A new period of excitability appears, however, after approximately 150-200 days in females that have dropped their young and are now lactating adults. In such female rats the least excitement is sufficient to trigger off convulsions.

A magnesium-deficient diet can turn a calf into a cow with a predisposition to tetany

This American experiment with rats is of particular interest in the present connexion, lactating cows and ewes being particularly susceptible to grass tetany.13 It provides us with two important pieces of information:
  • For a given deficiency of magnesium the lactating female is much more sensitive to phenomena triggering convulsions.
  • If a female has been reared on a magnesium-deficient diet 14 she will exhibit a more marked tendency towards convulsions during lactation.15
It is possible, therefore, that female calves that have been reared on rations containing little magnesium and/or have been grazing pastures that would upset their magnesium metabolism will subsequently exhibit a special tendency towards convulsions once they have become lactating cows. This is what happens on farms where the management practised favours disturbance of the magnesium metabolism: the "dietary history" of the calf can sensitize the future cow to tetany. These practical farming conditions obviously do not enter into play in many of the experiments undertaken by research centres.

The two phases of magnesium deficiency

There appear to be two phases in the development, in young growing rats, of the phenomena that accompany marked magnesium deficiency.
During the first phase, which is characterized by vaso-dilation, hyperaemia and hyperirritability, there is a considerable drop in the magnesium content of the blood plasma which falls from 2-7 to 0-4/100 c.c. (Figure 5).
The onset of convulsions, as the result of which magnesium is released by the muscles,16 causes the magnesium content of the plasma to rise suddenly. It will return to a normal level for a period. The convulsions thus appear to be a defence mechanism or, to use SELYE'S terminology, "a desperate adaptation syndrome". In effect, they enable a normal magnesium content to be re-established for a time in the blood plasma: a content that had fallen to a dangerously low level. They appear to be deputizing for defective endocrine mechanisms that are no longer capable of maintaining the magnesium in the blood plasma at a constant level.

Figure 5: Variations in the magnesium content of the blood plasma of rats deficient in magnesium.

During the second period of deficiency, characterized by under-nourishment, general debility and kidney lesions, the magnesium content of the blood plasma, although showing a tendency to diminish, remains more or less normal.17 During this period, however, the hyper-irritability persists and convulsive attacks can be brought on by a loud noise or any other disturbance. In other words, hyper-irritability and the tendency towards convulsions are almost as marked during this second deficiency phase as in the first when the serum contained less magnesium.18

Following an attack of tetany the magnesium in the blood serum of cows increases again

It would be assuming too much to transpose to all animals, and particularly to adult cows and ewes, these results obtained with young growing rats.19 It is noteworthy, however, that as long ago as 1930 SJOLLEMA, in Holland, had noted that when a tetany attack commences the magnesium content of the blood serum is low, whereas following the attack the content becomes relatively high. Twelve years later, in India, RAY, at the Izatnagar Research Institute, produced hypomagnesaemia and tetany by feeding young heifers a natural ration,20 low in magnesium. He recorded an immediate increase in the diminished magnesium level following the convulsions.21
This, then, is a general phenomenon. Consequently, this increase in the magnesium level in the blood serum, following a more or less marked and observed attack, may confuse the diagnosis. It is generally not until one or more cows in a herd have been attacked by tetany that the magnesium levels in the blood serum throughout the herd are determined. One is often surprised to find that these levels are relatively high. Figure 5 can explain these apparent anomalies: it is possible that certain beasts that have previously suffered from slight, unobserved tetany convulsions may exhibit a relatively high magnesium content in the blood serum 22 from the very fact of having suffered these moderately severe convulsions.

Hypomagnesaemia and tetany produced experimentally in ruminants fed on rations very low in magnesium

In view of the size of their rations, it has proved to be quite a difficult matter to compound for cows, and even for ewes, rations that contain only small quantities of magnesium.
At the University of Illinois MCALEESE and FORBES fed lambs aged 9-10 weeks on an artificial ration containing 0-03% magnesium and 0-33% calcium in the dry matter.23 After a few weeks on this diet the lambs became nervous and apprehensive. The magnesium content of their serum fell to 0-5 - 0-7 mg./100 c.c.24 and several suffered from convulsions. After six weeks four of the six lambs had died from tetany convulsions.25
However informative the hypomagnesaemia produced by F0RBES may be, there is the objection that it was done with artificial rations. Another American experiment undertaken at the University of Maryland used a natural regime, namely dried forage crops.
Cows from beef and dairy breeds were fed exclusively on dried timothy, the magnesium content in the dry matter of which was extremely low,26 0.08%.27 This diet lasted for 4-6 months, from 30 days before calving to 14 days after calving. The magnesium contents in the blood serum of these cows fell to very low levels, below 0-50 mg./100 c.c. and sometimes as low as 0-06 mg./100 c.c. There was no hypocalcaemia. Two of the three cows from beef breeds were attacked by tetany.28 This proves, therefore, that simple magnesium deficiency can trigger off tetany convulsions in cows as well as in rats.

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Notes



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  1. 
Note that the magnesium contents of these synthetic rations varied from 0-18 
to 5-00 mg. per 100 gm. of ration, or from approximately 0-20 to 6-00 mg. 
magnesium in 100 gm. dry matter.
    
    
The minimum magnesium encountered by the author in the dry matter of herbage 
is 0-05%, or 50 mg. magnesium in 100 gm. dry matter: this in the case of 
pastures having received regularly large quantities of
liquid manure. But there are many other imbalances in tetany swards which 
accentuate the effects of magnesium deficiency. *


    

    


  2. 
In almost all the experiments the total magnesium in the blood serum was
 measured and no account taken of the different forms of magnesium present 
in the serum. Magnesium occurs in blood serum in at least two forms which 
can be separated by ultrafiltration. It is thought that the
 ultrafilterable form of magnesium is ionized and constitutes 20-50% of 
the total magnesium. Ionized magnesium is the active form of the element
and it will be seen that some workers hold the opinion that the consumption
of very young grass produces in the blood a factor that blocks ionized 
magnesium, probably by means of chelatization. * 
    
       


    

    


  3. 
Sometimes, indeed, the calcium in the blood serum has been seen to drop.
* 
           


    

    


  4. 
Normal magnesium contents in the red corpuscles of rats vary from 6-O to 
9-5 mg. per 100 c.c. After 10 days of deficient feeding the content falls 
to 3-0 mg. per 100 c.c., but thereafter this level is apparently 
maintained. * 
    
       


    

    


  5. 
It will be seen that the magnesium content of the muscles was subsequently
observed to fall slightly as magnesium deficiency developed in rats.
 * 
          


    

    


  6. 
This question of calcification of soft tissues will be dealt with in greater 
detail below when studying magnesium-calcium antagonism. * 
    
       

    

    


  7. 
For further details see chapter 24. * 
    
       

    

    


  8. 
Vaso-dilation gives a reddish, shiny appearance to the readily visible parts 
of the skin, particularly the external parts of the ears, base of the claws, 
tongue, mucous membranes of the mouth and conjunctiva. * 
    
       


    

    


  9. 
BELANGER supposed that this hyperaemia (increased blood flow in a part of
the body) was caused by the histamine liberated in the mast cells as a 
result of the low content of magnesium in the blood serum. This theory 
seems to be confirmed by recent work at the University of Montreal.
* 
           


    

    


  10. 
As long ago as 1939 KRUSE'S findings showed that magnesium deficiency 
could be one of the causes of hypercholesteraemia. They demonstrated 
more generally that magnesium plays a considerable part in the 
metabolism of cholesterol and lipids in the blood.
    
    
This work appears to have received little attention until very recently when
 numerous investigations revealed the enormous part played by magnesium in
 thrombosis, athero and arterio-sclerosis.
 * 
          


    

    


  11. 
See the question of adrenalin, hormone of the emotions (chapter 21).
* 
                  


    

    


  12. 
This ration and the following contained 0-87% calcium (or about 1-02%. calcium 
in the dry matter). With a higher calcium content the tetany appeared more 
quickly (see chapter 15). * 
    
       


    

    


  13. 
See chapter 33. It will be seen, moreover, that this susceptibility to 
tetany on the part of the lactating female can be explained by increased 
thyroid activity.
 * 
          


    

    


  14. 
The phenomenon may also be at work, and more obviously perhaps, if the 
mother of this female was fed a magnesium-deficient diet during her 
gestation.
* 
           


    

    


  15. 
These females could be said to be suffering from "latent tetany" or 
"crypto-tetany".
    
    
The reader is referred in this connexion to the notable research on 
hypomagnesaemic tetany in Man carried out by the Belgian worker 
ROSSELLE. 
    
Rosselle, N. and Doncker, K. DE. "Cryptotétanie" 
(Latent-Tetany), Acta Clinica Belgica, 14, 162 - 172 [1959].

    Rosselle, N., and Doncker, K. DE. "Étude expérimentale et
 clinique d'une tétanie larvée" (Experimental and clinical
 study of a hidden tetany"), World Neurology, 2, 908 - 919 [1961].
 * 
    


    

    


  16. 
The muscle in action releases magnesium, probably from the intra-cellular
 region. (With regard to the magnesium reserve of the muscles see chapter 14)
  * 
          

    

    


  17. 
The magnesium content of the red corpuscles is reduced to half at the beginning 
of the first period, subsequently remaining constant for the rest of that 
period and throughout the second period. * 
    
       



    

    


  18. 
On the subject of hyper-irritability associated with an almost 
normal magnesium content of the plasma during this period an American 
worker writes: "The reduced magnesium content of the plasma is not 
directly responsible for the hyper-irritability." It is probable that 
this is too sweeping a statement and that it would be
preferable to say that the disturbance of the magnesium metabolism is 
not necessarily manifested in a diminution of the magnesium content of 
the blood serum.
    
    
Magnesium is primarily an intra-cellular element, and the magnesium
content of the blood serum, an extra-cellular fluid, possibly may not 
always be correlated with the intra-cellular concentration.
    * 
           

    

    


  19. 
It should be borne in mind that in the young growing animal part of the 
magnesium in the bones is mobilizable in case of need; this is not so in 
the adult animal. The same phenomenon is encountered in the young calf.
 * 
          

    

    


  20. 
Composed mainly of wheat straw. * 
    
       

    

    


  21. 
In three heifers made hypomagnesaemic in this way, the magnesium content 
of the blood serum (in mg./100 c.c.) rose after convulsions from 0-75 to 
0-93, from 0-81 to 1-10 and from 0-70 to 1-10. * 
    
       

    

    


  22. 
The susceptibility of these cows to tetany convulsions persists, as in rats.
* 
    



    

    


  23. 
The contents of other mineral elements in the ration are not stated. As 
EVERED remarked, this ration of MCALEESE and FORBES contained a great deal 
of corn cobs, thus being rich in phytate which can reduce the absorption 
of magnesium in the digestive tract. * 
    
       

    

    


  24. 
Hypocalcaemia was present simultaneously. * 
    
       

    

    


  25. 
Intravenous injections of 10 c.c. of a 10% magnesium acetate solution proved 
quite effective, although their improvement of the magnesium content in the 
blood serum was only transitory. * 
    
       

    

    


  26. 
Bear in mind that if forage crops are washed by rain while drying they 
lose a large part of their magnesium. * 
    
       

    

    


  27. 
It appears that timothy is low in magnesium (see Table 25).
* 
           

    

    


  28.   
It is a curious fact that the dairy breed cows, although their serum was 
very low in magnesium, did not suffer from convulsions.
*