CHAPTER 15

The calcium: magnesium balance of the ration and the role of the phosphates and sulphates in tetany

DUCKWORTH, for example, found that young rats on a diet of this nature (magnesium content 6 p.p.m.) died from convulsions after 12 days when the calcium content of the ration was 0-10%. If the calcium content was increased to 0-90%, however, the rats survived for only half the time, namely 6 days.¹

Guinea pigs were fed a ration very low in magnesium (0-005%) and containing 0-9%, calcium. The daily weight gain of these animals fell from 19 to 4 gm. when the phosphorus content (P) rose from 0-4 to 1-7%. At the same time the deposits of calcium (in the form of phosphate) in the heart, muscles and kidneys were of a very much higher order.⁵ The result was a greater requirement of magnesium with a ration rich both in calcium and phosphoric acid.⁶

Hypomagnesaemic tetany has been successfully produced experimentally by the administration of phosphates.⁷ In Norway ENDER established that the administration to sheep or cows of dipotassium phosphate reduced the magnesium content of the blood serum by about 15-30%. The effect was the same if the dipotassium phosphate was replaced by disodium phosphate: an indication that the phosphate anion is the cause of this effect on magnesium.
In Holland SJOLLEMA found that simultaneous administration of potassium (or sodium) acetate and dipotassium (or disodium) phosphate to cows previously attacked by tetany ⁸ gave rise to hypomagnesaemia ⁹ and possibly the appearance of tetany.¹⁰

"The most striking metabolic lesion we have noted in animals suffering from magnesium deficiency is the disturbance of the calcium metabolism."

MAYNARD, for example, recorded the results contained in Table 15. It will be seen that, for the same level of calcium (Ca) (1-28%) and phosphorus (P) (0-84%) in the ration,¹⁸ the calcium contents of the kidney, liver and heart increase considerably when that ration is deficient in magnesium (reduction from 0-40 to 0-07%). This phenomenon is particularly marked in the kidney, the calcium content of which (in 100 gm. dry matter) was 88 mg. in the control animals against 2229 mg., that is, twenty times more, in the animals on the magnesium-deficient diet. The result was the appearance of nephro-calcinosis, that is to say, a deposit of calcareous salts in the kidneys.¹⁹ This is one of the first pathological manifestations to appear in an animal deficient in magnesium.

Nephro-calcinosis caused by magnesium deficiency favours tetany

As will be seen in dealing with anatomical lesions observed in autopsies, calcification of the heart,²⁰ muscles, kidneys, etc., is almost always present in cows that have died from tetany, nephro-calcinosis apparently being the most common and most marked calcification. This deterioration of the kidneys resulting from upset of the magnesium metabolism is the more serious, as the kidney is an organ with very little capacity for regeneration.
Thanks to an adaptation mechanism, controlled mainly by the adrenal glands, the organism that absorbs absolute and/or relatively excessive quantities of potassium in grass excretes more potassium in the urine in order to avoid the injurious effects of an excess of this element. It is obvious that this defence mechanism can function efficiently only if the kidney is in perfect condition and if there has been no deterioration as a result of nephro-calcinosis: that is, as a result of calcareous deposits due to an insufficiency of magnesium in relation to the quantities of calcium and phosphorus present in the herbage.

Buccal administration of large quantities of sulphate causes hypomagnesaemia

The question of the role of the phosphates in the calcium-magnesium balance and of their possible influence on tetany cannot be passed over without saying a word at the same time on the probable role of the sulphates. This problem derives its importance from the fact that the application of sulphate of ammonia to the soil, which raises the sulpher content ²¹ of the herbage, appears to favour hypomagnesaemia and tetany (Table 24).
ENDER, in Norway, observed that when sheep were fed large quantities of sodium (or potassium) sulphate,²² sulphur, sulphite or thiosulphate there was a sudden drop in the magnesium content of the blood serum and a simultaneous increase in its phosphorus content. This sulphate administration makes the level of hydrogen sulphide in the rumen rise.
In another connexion KOETSVELD has emphasized that grass tetany is most frequent in spring, and it is at this time that the herbage's content of total and of mineral sulphur is at its highest. In addition, the Dutch worker established that the content of sulphate ions (S0₄) in the blood serum was slightly higher in cows suffering from tetany.²³ It is not impossible, therefore, that the sulphur content of the herbage contributes towards tetany, although the quantities of sulphates used in the various experiments reported here are much higher than those ingested by grazing animals. Nevertheless, this is another fact apparently confirming a possible part played by sulphur in tetany caused by very young grass.

Very young grass considerably increases the hydrogen sulphide content of the rumen

The effect of very young, spring grass in considerably increasing the production of hydrogen sulphide in the rumen is exactly the same as that of a sodium sulphate supplement in the ration. This is illustrated in Figure 7.

Figure 7: Greatly increased hydrogen sulphide content in the rumen liquid following the ingestion of very young grass

It has just been said that there is a maximum content of sulphate ions in young, spring grass, and this may possibly be one of the factors contributing to the very high level of hydrogen sulphide production when the animal goes out to grass in the spring. It is probable, however, as MEYER suggests, that this rapid and intensive production of hydrogen sulphide is due, above all, to the fact that the crude protein of young grass, by its very nature, is very rapidly decomposed by the rumen bacteria. The result is that the sulphur amino acids (cysteine (or cystine) and methionine) are equally subject to this rapid decomposition, giving rise to an exaggerated increase in the hydrogen sulphide content of the rumen, in exactly the same way as the rapid breakdown of the proteins is the cause of excessive ammonia production (see Figure 13).
It still appears difficult to explain how this excess of hydrogen sulphide ²⁴ is able to favour the appearance of hypomagnesaemia and grass tetany.

1. It will be seen that from the point of view of neuro-muscular transmission calcium and magnesium are antagonistic to the ejection of acetyl choline at the nerve ending and are analogous in their effect on the stability of the muscle end-plate. It appears, therefore, that under the conditions of these experiments it is the antagonistic effect of calcium and magnesium that is dominant. *

2. The same antagonistic effect of calcium on magnesium is observed in the animal as is discernible under certain conditions in the soil and in the plant (see Figure 4). *

3. It has just been seen in the preceding chapter that the addition of calcium lactate to milk accelerates the manifestation of hypomagnesaemia in milk calves. *

4. A high content of phosphorus in the ration has been seen to increase the antagonistic effect of potassium with regard to magnesium. *

5. Magnesium deficiency in itself gives rise to calcification of this nature in certain organs. *

6. O'DELL determined the magnesium content necessary in a ration to get optimum growth results in guinea pigs. With a ration containing in the dry matter 1-06% calcium (Ca) and 0-47% phosphorus (P), a magnesium (Mg) content of 0-10% is sufficient. But if, for the same calcium content, the phosphorus (P) content is increased to 2%, then 0-28% magnesium (Mg) is required for optimum growth. *

7. There is a phosphate tetany that can be caused experimentally by the intravenous injection of neutral, alkaline or slightly acid sodium phosphate. Associated with this tetany is a diminution in the calcium content of the blood serum. *

8. That is to say, "physiologically conditioned" to the factors causing tetany. *

9. The magnesium content of the blood serum fell to very low levels (0-1 - 0-4 mg./100 c.c.). At the same time the phosphoric acid content of the blood serum rose. SJOLLEMA states that the urine of cows suffering from tetany has a higher phosphorus content, which he considers to be indicative of a change in the phosphorus metabolism. *

10. Buccal administration of magnesia (MgO) proved effective against this hypomagnesaemia, as is generally the case. *

11. There appears, moreover, to be a reciprocal relation between magnesium and phosphoric acid in plant nutrition. Magnesium would act specifically as a transporter of phosphorus. Workers at the University of Wisconsin showed, for example, that the application of magnesium fertilizer increased the phosphorus content of peas more than increased dressings of phosphoric fertilizers. From this they concluded that an insufficiently high level of magnesium in the soil can reduce the effectiveness of phosphoric fertilizers. *

12. Which can have undesirable effects on the health of the animal, and particularly on its fertility. *

13. As O'DELL pointed out, there is in the animal as in the plant a reciprocal effect of magnesium on phosphorus, and one of the main effects of magnesium deficiency is to upset phosphorus metabolism. *

14. In the milk calf buccal administration of a magnesium salt effects a rapid rise in the calcium content of the blood serum that had fallen to a low level simultaneously with the magnesium content. *

15. In rats deficient in magnesium it was noted that the amount of calcium absorbed was equivalent to the total amount of calcium and magnesium absorbed in the normal rat group. From the first day of magnesium deficiency less calcium was excreted in the urine, despite the presence of hypercalcaemia.
       There was no change in the glomerule filtration level, and it is probable that the reduction of calcium excretion in the urine is due to increased absorption of the filtered calcium by the cells of the tubules.
        MCINTYRE considered that a more probable explanation of these findings was that there is a common transport system for calcium and magnesium not only in the digestive tract but also in the renal tubules. This seems to be confirmed by in vitro experiments undertaken by SCHACHTER revealing that, in the isolated intestines of rats, rabbits and guinea pigs, less calcium was transported through the organ as the content of magnesium ions increased. *

16. The hypertrophied kidneys have a bleached appearance and may often weigh double the normal weight. Very severe calcification is present.
        Recent work by GERSHOFF has shown that in rats deficient in pyridoxine and magnesium, deposits of calcium oxalate form in the kidneys and that there is an inverse relationship between the extent of these oxalate deposits and the magnesium content of the ration. *

17. The liver is marked by striations and small white spots. It is a case of local necroses accompanied by calcification. *

18. On the average, pasture grass contains 0-40 - 0-90% calcium in the dry matter. White clover has a mean content of 1-70% calcium in the dry matter, and the figure may be as high as 2-20% in lucerne. Obviously these figures can vary within wide limits (see Tables 26 and 27). *

19. In 1962, at the University of Oklahoma, SMITH confirmed that magnesium deficiency very quickly gave rise to pathological changes in the renal tubules of rats, thus upsetting the functioning of the kidney. *

20. The result is a persistent alteration of the electro-cardiogram in the case of cows that have previously suffered from tetany (the RT and PT intervals are shorter).
       In addition, the lower the magnesium content of the blood serum, the more rapid the pulse. *

21. Sulphate of ammonia seemed to be more toxic in its effect than the others. Although it did not reduce the magnesium content of the serum, however, it did reduce the calcium content.
       The administration of large quantities of the various sulphates was accompanied by fairly severe scouring.
       A.I.V. silage, which is made with sulphuric acid, produced the same effects as sodium sulphate. *

22. Which rose from 4-6 to 8-10mg./100c.c. It is not stated whether there was any increase in the sulphate ion content of the blood serum. *

23. Normal serum contains 10-15 mg./ 100 c.c. SO₄ ions against 15-20 mg. in cows suffering from tetany. The difference appears to be slight. *

24. Hydrogen sulphide is known to be able to pass easily through the walls of the rumen into the bloodstream; this is brought to our attention by MEYER. It is not impossible, therefore, that it may be able to produce toxic effects directly by combining with the haemoglobin in the blood. As yet, however, there is no proof of this.
        It is equally possible that hydrogen sulphide forms non-assimilable compounds with magnesium, as happens with copper, the sulphur of which cannot be resorbed. *