CHAPTER 23

Sodium deficiency and its effect on the adrenal cortex

Sodium requirements of the cow

On the basis of these and other findings the Cornell workers estimated the sodium requirements of a cow to be as follows:

1.	A 10-cwt. [500-kg. ] cow not in milk requires per day:8 20 gm. salt, which is 12 gm. sodium.
2.	To this must be added per 2-2 gal. [10 litres] milk about 40 gm. salt, or 24 gm. sodium. A 10-cwt. [500-kg.] cow, therefore, yielding 3-3 gal. [15 litres] of milk, requires per day: 80 gm. salt or 50 gm. sodium.9

Minimum sodium content of grass necessary to satisfy the requirements of the cow

On the cautious assumption that a 10-cwt. [500-kg.] cow harvests an average of 22 lb. [10 kg.] dry matter per day,¹⁰ then if the requirements of the cow yielding 3-3 gal. [15 litres] milk are to be met, the dry matter of the herbage must contain: 0-50% sodium.
On the assumption that the cow is dry, the minimum content must be: 0-12% sodium.¹¹
It is understood that these requirements can vary as the result of many factors, particularly the potassium content of the ration, which increases the sodium requirements of the animal.¹² It appears, wise, therefore, to consider that the dry matter of the herbage must never contain less than 0 - 25% sodium (Na) and that it is even desirable that it should contain 0 - 50 % in the case of high-yielding dairy stock.
Even the inadequate minimum figure is very rarely, if ever, attained in herbage that has received potassium, small though the dressings may be, in the form of potassium fertilizer or liquid manure. Consideration of Tables 26 and 27 produces a definite feeling of anxiety,¹³ as does the statement in a Dutch report that 91-2% of the hundreds of herbage samples examined contained less than 0 - 18 % sodium. This helps to explain the "salt hunger" so frequently observed today in the grazing animal, especially on pastures with a high incidence of tetany.
Fertilizer dressings containing sodium have been seen to increase clearly and even considerably the sodium content of herbage. In addition, the question of sodium supplements for the animal will be examined below. But, to understand how this deficiency of sodium in herbage can contribute towards tetany, its effects on the adrenal cortex will now be examined.

A ration low in sodium considerably increases the production of aldosterone by the adrenal cortex

The hormones of the adrenal cortex,¹⁴ especially the mineralo-corticoides (such as aldosterone) have a marked influence on the excretion of potassium and sodium in the urine. An injection or increased secretion of aldosterone by the adrenal ¹⁵ cortex, for example, has the following simultaneous consequences.

1.	Increased excretion of potassium in the urine;
2.	diminution in the excretion of sodium in the urine.16

In other words, greater secretion of aldosterone by the adrenal cortex tends to impoverish the organism with regard to potassium and retain sodium.
After rats had been fed for a period of a few dozen days on a ration extremely low in sodium, hypertrophy of the zona glomerulosa ¹⁷ (the outermost layer) and increased aldosterone production ¹⁸ were ascertained. Likewise, the increased quantities of potassium ¹⁹ ingested causes the secretion of aldosterone to increase: which is admirable proof of the fact that it is the potassium : sodium ratio that is the deciding factor.²⁰
It is interesting to note the speed with which these changes in the adrenal cortex take place in animals deficient in sodium or who have been the victims of such a deficiency, in so far as the latter has not yet damaged the adrenal cortex:²¹ four days after the rats receive the sodium-deficient ration the changes in the different zones of the adrenal cortex have already reached their maximum, where they remain for the forty days of the experiment, a period during which no further aggravation of the biochemical lesion takes place. When, after 43 days of experimentation, the normal quantity of sodium chloride is added to the ration the hypertrophy of the zona glomerulosa is already diminished one day later, and another day later still the layers of the adrenal cortex have returned to normal.
Here, then, is a further example in the animal of the metabolic antagonism of potassium and sodium, which is very marked in the plant also.

Thanks to the adrenal cortex the cow adapts itself to herbage low in sodium and rich in potassium

To use SELYE'S terminology, inadequate sodium and/or excessive potassium in the ration creates a "stress" which will cause an adaptation reaction consisting of hypertrophy of the zona glomerulosa in order that it may secrete increased quantities of aldosterone and thus reject as much potassium and retain as much sodium as possible ²² in the urine. This adaptation mechanism of the adrenal cortex will permit the organism to "suffer" as little as possible from the excessively high potassium: sodium ratio in the ration.
The herbage that causes tetany is too rich in potassium and extremely low in sodium, due to excessive dressings of potassium fertilizers (solid or liquid). Before leaving this subject of sodium and the adrenal cortex, therefore, it is of interest to examine the very clear defence reaction on the part of the organism of the cow put out to graze such a sward. This is illustrated by Table 18. Cows were fed herbage of normal composition ²³ that had not received potassium fertilizer. Then they received herbage to which very large quantities of potassium fertilizers had been applied and which were very rich in potassium with a low content of sodium.²⁴
To combat this imbalance in herbage composition (caused by excessive dressings of potassium fertilizer) the organism, through the action of the adrenal cortex,²⁵ reduces the sodium content of the urine from about 160 to about 8 mg./100 c.c., that is, twenty times less, while doubling the potassium content. This, in the case of the dairy cow at grass, is the same finding as was reached in many other experiments concerning rats, dogs, humans, etc., receiving a ration deficient in sodium and rich in potassium: namely, that the organism tries to:

a.

get rid in the urine of as much as possible of the potassium supplied to it in excessive quantities by the herbage;

b.

retain the maximum amount of sodium, which the herbage supplies in extremely small quantities.26

TABLE 18: Immediate adaptation mechanism of the cow when fed herbage low in sodium and rich in potassium

Adaptation of the cow to herbage rich in potassium and low in sodium is possible only if the kidneys and adrenal glands are in perfect condition

The organism of the cow consuming this herbage extremely low in sodium and excessively rich in potassium will only be able to rid itself in the urine of the excess of potassium and retain as much sodium as possible on two conditions:

the renal filter 27 must be intact;

the adrenal cortex must not be damaged.

Unfortunately it is known that tetany-producing herbage, because of its tendency to give rise to hypomagnesaemia, causes calcium to be deposited in the kidneys.²⁸ A moderate and even transitory deficiency of magnesium, recurring chronically, is sufficient to produce severe calcification of the kidneys, or, to be more exact, of the renal tubules. The organism's mechanism for adaptation to an excess of potassium ²⁹ and a deficiency of sodium in the herbage will then no longer be able to function satisfactorily. In addition, to achieve this change in the movements of potassium and sodium in the kidney, the organism is obliged to hypertrophy the zona glomerulosa of the adrenal cortex in order to considerably increase the secretion of aldosterone which regulates the excretion of potassium and retention of sodium. This effort is the more marked as the calcification of the kidney checks these movements. The result is accentuated hypertrophy of the zona glomerulosa of the adrenal cortex. Finally, the "syndrome of exhaustion" succeeds the "syndrome of adaptation": the adrenal cortex is degenerate and necrosed and no longer able to fulfil its functions. This has been seen to be the case in many cows that have died from tetany.

The previous "dietary record" of the animal determines its capacity for adaptation to tetanigenic herbage

It cannot be sufficiently emphasized that it does not amount to the same thing to use in experiments on grass tetany cows that have or have not already suffered, repeatedly and chronically, deficiencies of magnesium and sodium, moderate though these may be. If, in consequence of such deficiencies, cows have kidneys overloaded to some degree with calcium deposits and adrenal glands that have suffered some deterioration, their capacities to resist effects produced by mineral imbalances in the herbage will vary. It can even be said that this state of the kidneys and adrenal glands, resulting from the previous "dietary record" of the animal ³⁰ contributes as much as, if not much more than, hereditary characteristics to the individual susceptibility of cows to tetany.
The farmer, then, is dealing with cows that have suffered the various effects of tetanigenic herbage since birth or, to be more exact, since conception.

1. The ration comprised corn silage, concentrates and forage, particularly timothy hay, a species which is especially low in sodium. *

2. They were given water from a stream containing no sodium at all. *

3. Note that this was iodized salt. The question of the effect of this iodine on the experimental animals was not dealt with in this study. *

4. Some were able to be cured by the daily administration of 100 gm. salt. This was a deficiency of sodium and not of chloride, for the administration of bicarbonate of soda produced the same effects as the salt. *

5. Severe hypertrophy of the adrenal glands was seen above to be common in cattle victims of grass tetany. *

6. This was confirmed, for example, on herbage very low in sodium (0-07%) and rich in potassium (2-90% in the dry matter), that is, having a K/Na weight ratio of 41, which is extremely high. *

7. For the role of sodium in bone metabolism, see FORBES. *

8. These are round figures. The sodium chloride must be multiplied by 0-6 to get the amount of sodium it contains. *

9. With all the reservations that must surround these requirements, which can vary very considerably as a function of multiple internal and external factors.
   FRENS estimated that a cow weighing 10 cwt. [500 kg.] and producing 4-4 gal. [20 litres] of milk per day has a daily requirement of 23 gm. sodium, which is obviously lower than the Cornell figure. Moreover, FRENS draws attention to the fact that his calculations do not take into account increased sodium requirements resulting from the consumption of young grass very rich in potassium. *

10. Frequently it harvests even less. See Grass Productivity (pp. 77 and 82). *

11. FRENS' basis is a daily sodium requirement of 23 gm., and he assumes that a cow "harvests" an average of 29 lb. [13 kg.] dry matter per day. From this he deduces that the minimum sodium content in the dry matter of herbage must be 0-18%. *

12. As Nutrition Reviews, examining Australian experiments regarding the supplementary feeding of fattening sheep with salt, remind us: "These results tend to confirm the current opinion that farm animals require salt to compensate for the antagonistic effect of a high content of potassium in foodstuffs." *

13. This inadequacy of sodium does not give rise to visible deficiency symptoms in the herbage, but it is extremely dangerous for the animal. As was stressed in dealing with the problem of magnesium, this illustrates the danger of the over-simple logic behind the statement: "So long as there are no pathological symptoms in the plant there is nothing to fear for the animal." It has already been said that iodine and cobalt, apart from magnesium and sodium, are sufficient to make the error in such reasoning quite clear. *

14. Briefly and in very simplified terms it may be stated that the adrenal cortex comprises three layers (or zones) which, starting from the outside inwards (that is, towards the medulla), are as follows:
    
    1. Zona glomerulosa, the centre of the formation of the most of the mineralo-corticoides, hormones as aldosterone and D.O.C., which affect mainly the metabolism of the mineral elements, particularly potassium, sodium and magnesium.
    2. Zona fasciculata, where the greater part of the gluco-corticoides are formed, that is, such hormones as cortisone, 17-oxy-corticosterone, hydrocortisone, all of which primarily affect carbohydrate metabolism.
    3. Zona reticularis, where the androgen hormones are formed (also secreted by the testes).
    
    The divisions, both from the point of view of the zones and the distribution of hormone production between these zones, are far from being absolute. *

15. More correctly, by the zona glomerulosa of the adrenal cortex. *

16. Note that within the normal limits of aldosterone concentration (as well as of the other mineralo-corticoides) this hormone exerts a less-marked influence on the excretion of potassium than of sodium in the urine. *

17. At the same time there is often atrophy of the zona fasciculata (the central zone) that produces the gluco-corticoides. It has been proven, moreover, that a diet low in sodium impoverishes the blood plasma of rats with regard to corticosterone, a gluco-corticoide secreted by the zona fasciculata. In other words, as PFEFFER has stressed, sodium deficiency causes "dissociation" of the functions of the adrenal cortex by diminishing the production of gluco-corticoides and at the same time increasing production of the mineralo-corticoides. *

18. And of the other mineralo-corticoides. It has likewise been shown that feeding humans with a ration low in sodium stimulates aldosterone secretion, increased quantities of which appear in the urine. *

19. Cf. P. 113 for the influence of potassium on the adrenal medulla, which is an extension of the nervous system. *

20. Administering a potassium supplement with a ration rich or low in sodium does not amount to the same thing. LARAGH'S work on the mechanisms of aldosterone secretion by the adrenal cortex has shown, for example, that buccal administration of potassium chloride to dogs causes hyperpotassaemia only if the animals were simultaneously deficient in sodium. These two conditions are realized in young grass that has received excessive quantities of potassium fertilizer. *

21. Irreversibly. *

22. In fact, it is a question of much more complex balances. Unfortunately, it is impossible within the framework of this book to examine the influence of the mineralo-corticoides on the exchange of sodium and potassium between intra- and extra-cellular fluid. For example, buccal administration of potassium chloride to humans deficient in sodium causes an increase in the sodium content of the blood serum although the sodium balance is unaltered. But the potassium administered releases in the cells sodium ions, which pass into the extra-cellular liquid, increasing the latter's content of this element.
    In effect, the mineralo-corticoides influence the ion balances of all the tissues. *

23. 0-57% sodium and 1-89% potassium in the dry matter. Weight ratio of K : Na is 3 - 33. *

24. Namely, 0-13% sodium and 3-30% potassium in the dry matter or a K : Na weight ratio of 25 - 04, which is eight times higher than that of normal herbage that has received no potassium fertilizer. Note that the maximum acceptable for this ratio is 8 but that it is not wise to exceed 5. *

25. That is to say, thanks to increased secretion of mineralo-corticoides particularly aldosterone. *

26. Relatively few accurate data are available on variations in the sodium content of the blood plasma during grazing. From recent work published by STORRY of the Rowett Institute it appears that when the animal goes out to grass in spring there is a slight fall in the sodium content of the blood plasma while the sodium content of the red corpuscles increases. *

27. There are many variants and not a few points that still need clarification, but it is generally assumed today that the proximal tubule of the kidney reabsorbs all the potassium filtered by the glomerule and that the potassium excreted in the urine stems from the distal tubule secretion which has the capacity to exchange potassium against sodium ions. It is likewise assumed that a very large fraction (about 80%) of the sodium of the glomerular filtrate is reabsorbed in the proximal tubule and that variations in the urinary excretion of sodium are due to variations in the reabsorption of the remaining fraction (20%) which Passes into the distal tubule where the reabsorption mechanism, as has just been stated, is closely linked with the tubular secretion of potassium ions. These exchanges are regulated, directly or indirectly, by the mineralo-corticoides, especially aldosterone which is secreted by the adrenal cortex. *

28. The effect is accentuated if the herbage is rich in calcium and phosphoric acid. *

29. LATTEUR has rightly stressed the importance of the renal system being in good condition if the animal is to adapt itself to the excess of potassium in the ration. He writes: "Experimental tetany cannot be produced by potassium in cows whose renal filter is in good condition." *

30. Regarding the role of the "dietary record" in determining the individual character of the animal and its susceptibility to tetany. It will be seen, moreover, that deterioration of other organs, such as granulo-fatty degeneration of the liver, can accentuate the susceptibility of the animal to tetany. *