CHAPTER 14

Hypomagnesaemic tetany of milk calves and the magnesium reserves of the organism

This is illustrated by Figure 6, which shows that as the milk calf grows older the magnesium and calcium levels ⁵ in its blood serum progressively diminish.⁶ Convulsions ensue when these levels become dangerously low.

SMITH, for example, recorded the figures contained in Table 14. These were obtained by depriving calves of magnesium by means of special rations (artificial milks). As the magnesium deficiency became accentuated the following phenomena were manifested:

The percentage of ash in the bones did not alter perceptibly. On the other hand, the percentage of magnesium 13 in the bone ash fell steeply from the normal 0-76 to 0-29 that is, less than half the normal.14

The magnesium lost from the calf's bones is replaced by calcium

In the young calf each magnesium ion that leaves the bones is replaced by a calcium ion.¹⁵ In other words, the loss of magnesium from the hones does not involve for them a simultaneous loss of calcium. In most cases, indeed, it appears that the percentage of calcium in the bones increases as the percentage of magnesium diminishes. The process of impoverishing the bones with regard to magnesium probably takes place on the surface of the bone crystals following an exchange ¹⁶ between the atoms.¹⁷ The result is a rapid increase in the calcium : magnesium ratio as the magnesium deficiency becomes more marked.¹⁸ Table 14 shows that the Ca:Mg ratio, normally 52-55, rises to 91-135 in the magnesium-deficient calf. Conversely, when a magnesium supplement is fed to the young animal stricken with hypomagnesaemia, magnesium is again deposited in the bones, enabling them to build up their reserves once more. The calcium : magnesium ratio consequently diminishes.

The content of magnesium in the bones of cows that have died from tetany is not reduced

In the young animal, therefore, almost the whole skeleton acts as a source of magnesium mobilizable in case of need. The same is not true of the adult animal, the greater part of the magnesium in whose skeleton is metabolically inert. In the cow, therefore, the magnesium of the skeleton is no longer available to help to maintain the magnesium content of the blood serum at a constant level. This explains why, in the case of cows that have died from grass tetany, analysis reveals only a very small diminution, or most often no diminution at all,¹⁹ in the magnesium content of the bones, whereas it has just been seen that the bones of young calves that have died from hypomagnesaemic tetany can have lost up to 60% of their magnesium. It is clear, therefore, that the adult animal does not have available in the bones of its skeleton the reserve of mobilizable magnesium that is at the disposal of the young calf, or, more generally, the young animal. This "stabilization" of the magnesium in the bones is accentuated with age,²⁰ which would explain the tendency towards hypomagnesaemic grass tetany found in older cows.²¹

Low reserve of mobilizable magnesium in the muscles of the adult animal

Unlike the very young animal, therefore, the adult animal does not possess a reserve of mobilizable magnesium in its bones. The question has been asked, however, whether there is not possibly ²² a mobilizable reserve of magnesium, small though it may be, in the organism of the adult.²³
In 1958 MCINTYRE and DAVIDSON, contrary to different experiments undertaken previously, observed that the magnesium content of the muscles diminishes as magnesium deficiency develops²⁴ in rats. This finding was brilliantly confirmed in 1959 by one of these two scientists using radio-active magnesium. He succeeded in demonstrating that, in the adult rat, magnesium is present in the muscles in two forms:

	a rapidly exchangeable form;
	a form that is only very slowly exchangeable.25

In 1960 HANNA and MCINTYRE, using aldosterone injections in adult rats, came to the conclusion that this hormone had a direct effect on the muscle cells, causing them to lose magnesium.²⁶
This experiment confirms, therefore, not only the presence of a small mobilizable reserve of magnesium in the muscles but also that a hormone, aldosterone, secreted by the cortex of the adrenal glands, influences the movements of the mobilizable magnesium of that reserve. All the consequences of this will be better understood when it is realized that the low sodium content of the ration characteristic of tetany-producing pasture increases considerably the secretion of aldosterone. Indirectly, therefore, the extreme poverty of the herbage with regard to sodium will have a marked influence on the movements of the small mobile reserve of magnesium in the muscles.

The small reserve of magnesium in the muscles is not effected in exactly the same way in all forms of grass tetany

It must be stressed that this reserve of magnesium in the muscles of the adult animal is very small and apparently capable of only very slow mobilization ²⁷ in most normal circumstances. It can play a very important part, however, in the phenomena associated with grass tetany. From the practical point of view its consequences are as follows:

	Previous administration of magnesium does not allow the animal to accumulate reserves to improve its resistance to a subsequent period of deficiency.
	The protective effect of a magnesium supplement administered during a period of deficiency ceases almost immediately this supplementation stops.

It will be seen that under-feeding gives rise to slow hypomagnesaemia, which indicates that these few reserves of magnesium are gradually exhausted.
In spring grass tetany physiological shock is present, due probably to the reduced resorption of magnesium in the digestive tract and at the same time to a disturbance of the neuro-endocrine mechanisms ²⁸ that keep the content of the blood serum constant, causing the latter to fall rapidly before the small, slowly mobilizable reserves of magnesium in the muscles have had time to play their part.²⁹
Some authors are of the opinion that this difference in the movements of the magnesium reserve in the muscles may be the explanation for the slight effect achieved by magnesium injections in cases of grass tetany caused by under-feeding. In such cases it would appear that a single injection is incapable of replenishing the reserves, a replenishment that can take place only very slowly, at the same rate as they are exhausted. Many points remain to be clarified, however.

1. It likewise attacks suckling calves at grass. *

2. With hypomagnesaemia in calves there is no vasodilation or hyperaemia, as in rats deficient in magnesium. A certain exophthalmus is observed. *

3. In Research Institutes it has been found that the introduction of the needle to take a blood sample is sometimes sufficient to produce convulsions. *

4. This lower magnesium content in the blood serum is correlated with a considerable reduction in the excretion of magnesium in the urine. The same phenomenon is encountered in cows deficient in magnesium. *

5. BLAXTER is of the opinion that this diminution in the calcium content of the blood serum is due not to a deficiency of calcium but to a "metabolic rearrangement". The exchanges that take place between calcium and magnesium ions on the surface of the bone crystals of young animals will be dealt with below. *

6. The copper content of the blood serum also diminishes. See the observations made by Mrs. ALLCROFT on the author's own calves as reported in Soil, Grass and Cancer (pp. 59-60). *

7. 28 gm. magnesium carbonate per calf per day. *

8. Some workers have noted that the addition of Vitamin D to milk (which contains relatively little of this vitamin, particularly in winter) could lessen or suppress hypocalcaemia in these calves. The results are highly irregular. It has been wisely concluded, therefore, by SMITH that the primary cause of hypocalcaemia is not a deficiency of Vitamin D, although in certain exceptional cases large Vitamin D supplements could be effective. *

9. In fact, it has been observed by ALLCROFT that the addition of calcium lactate to milk accelerated the appearance of hypomagnesaemia in the milk calf. It will be seen in the following chapter that a high content of calcium in the ration accentuates the effects of magnesium deficiency. *

10. Chapter 12 addressed the question of magnesium resorption in the digestive tract. *

11. This is the percentage of apparent digestibility. *

12. SMITH has been able to show that this inferior utilization of magnesium in older milk calves does not result from a particular effect on the part of the milk, but is a normal physiological phenomenon manifested by the animal.
        It appears, moreover, in a more general way, that magnesium requirements increase with age, as has been observed in young dogs. *

13. No diminution in the magnesium of the soft tissues has been observed, even in calves with a very high degree of hypomagnesaemia. *

14. This impoverishment of the bones of the growing animal with regard to magnesium makes them very fragile, as was noted by LAVOLLAY as long ago as 1936. *

15. This phenomenon is explained by a simple exchange between the ions of the extra-cellular liquid bathing the bone cells and the ions present on the surface of the bone crystals. The surface of the crystals of the bones of the young animal act in effect as a reservoir of magnesium from which a certain amount is removed when the demands of the tissues increase, as in the case of the young growing animal not getting sufficient magnesium in its diet (or resorbing only an inadequate percentage).
        Conversely, absorption of magnesium by the bones of the young animal can take place only if a relatively high content of magnesium ions is maintained in relation to the calcium ions in the extra-cellular liquid bathing the surface of the crystals.
        The exchanges do not take place with equal rapidity, however, in both directions: deficiency experiments with calves indicate that it takes 40-50 days to deprive the skeleton of its reserve of labile magnesium. To reconstitute this reserve again, however, takes very much longer. *

16. Note that excessive magnesium in the ration, particularly of young animals, can have a rachitogenic effect, causing heavy losses of calcium and phosphorus. *

17. DUCKWORTH estimates that one-third of the bone magnesium in young rats is easily exchangeable. *

18. BLAXTER considers that a calcium : magnesium ratio of less than 60 : 1 is to be considered as normal. If the ratio reaches 90 : 1, it is a sign of magnesium impoverishment. The higher the ratio above 90 : 1, the more serious the magnesium deficiency and the greater the danger of tetany. Note that the method of analysing bones can be applied to the living calf, a caudal vertebra being removed from the tip of the tail. *

19. The ash of the bones of healthy adult cows has been found to contain 0-42 - 0-64% magnesium compared with 0-45 - 0-67% in the case of bovine victims of tetany. For the corresponding ash contents in the bones of calves see Table 14. *

20. BLAXTER considers that this "stabilization" of magnesium in the animal as it grows older is due to the three following factors:
    
    • alteration of the proportion of magnesium present on the surface of the bone crystals relative to the bones as a whole;
    • change in the rate of bone recrystallization;
    • alteration of the ionic balances in the extra-cellular liquid.
    *

21. See Table 31. it appears that the tendency towards hypocalcaemia increases even more rapidly with the age of the cow than the tendency towards hypomagnesaemia.
        TAYLOR believes that magnesium occurs in the bones in two forms, the one relatively soluble, the other relatively insoluble in dilute acids. The difficulty for the older animal in mobilizing the small fraction of soluble magnesium in the bones appears to be the reduced blood circulation in its osseous tissues. This is even more true of calcium, and would explain the greater incidence of milk fever in adult cows as well as the higher percentage of hypocalcaemia in cows attacked by hypomagnesaemic tetany at an older age. *

22. It has been seen that the magnesium content of the erythrocytes in animals deficient in magnesium is diminished. A very small amount of magnesium that can be considered as mobilizable may possibly be released in this way. *

23. Certain experiments conducted with human adults had already led to the supposition that such a reserve, though small, did indeed exist, although the storage organ (or organs) could not be determined. *

    

24. It is interesting to note that the potassium content of the muscles diminishes simultaneously in such a way that the potassium: magnesium ratio (K/Mg) remains more or less constant in the muscle throughout the deficiency. *

25. It was assumed that the most rapidly exchangeable magnesium of the muscle existed in the form of ions in the intra-cellular fluid, in physico-chemical balance with the magnesium of the extra-cellular fluid. The slowly exchangeable magnesium fraction would be in combination with intra-cellular anions.
        It should be remembered that magnesium is principally an intra-cellular element. Its concentration in extra-cellular fluid (blood serum, for example) is of the order of 2-40 mg./100 c.c. against 36-50 mg./100 c.c. in intra-cellular fluid, or fifteen times more.
        The magnesium content of the intra-cellular fluid, in the cells of the neuro-muscular system in particular, is probably correlated to a much greater degree with the convulsions of tetany than the magnesium content of the blood serum. In practice, however, practically all that can be easily determined is the magnesium content of the extra-cellular fluid. Finally, it should be noted that work with radio-active magnesium has shown that magnesium can traverse the cell membrane. *

26. The important role of aldosterone in magnesium metabolism will be dealt with in Chapter 24. *

27. There is one particular case where this small reserve appears to be rapidly mobilizable, namely, tetany convulsions, which are accompanied by the sudden liberation of the magnesium in the muscles to increase the magnesium content of the blood serum that has become very dangerously low (Figure 5). *

28. Not to mention the possible effect of particularly tetanigenic, factors. *

29. It is not impossible that shock of this kind may be superimposed on the effect of underfeeding. *