CHAPTER II
PATHOGENESIS AND ETIOLOGY
Table of Contents At the outset it may be stated that there is no longer any reason to doubt that adult scurvy and infantile scurvy are one and the same disease, having an identical pathogenesis. For many years, far longer than the facts warranted, there was discussion whether Barlow's disease was true scurvy or merely a form or a complication of rickets, or perhaps a distinct hemorrhagic disease. This question may be relegated to the past, so that we may proceed to consider the pathogenesis of scurvy in the infant and in the adult under a common heading.
There is no need of studying all the theories which have been advanced to account for scurvy. They have been manifold and most of them have died a natural death. For many years the potassium deficiency theory, suggested by Garrod, gained wide acceptance. That scurvy should be attributed to a lack of this salt is readily comprehensible in view of the abundance of potassium in the antiscorbutic foodstuffs, the fruits and the vegetables. It was not long before it was evident that this was not the correct solution, as the salts of potassium served neither to prevent nor to cure scurvy. This theory was accordingly modified to include only organic potassium. Experiment, however, failed to support the validity of this hypothesis, and it was gradually abandoned.
Another theory which had a short but popular career was the citric acid theory, which was maintained vigorously by Netter. This explanation seemed logical in view of the marked potency of the citrous fruits, and particularly when it was shown that human milk contains a greater percentage of the salts of citric acid than cow's milk, and that some of these salts are lost in the course of heating. This hypothesis withstood neither the practical test nor chemical investigation. It was found that the various salts of citric acid, either singly or in combination, are unable to cure scurvy. This treatment has been employed repeatedly on man and on animals with little or no success; we also have resorted to it in vain. It was shown, furthermore, that it rested on an insecure chemical basis, as boiled milk contains but 0.1 g. per litre less citric acid than raw milk-an amount which is negligible from a therapeutic point of view.
Before considering what may be termed the prevailing theories, a few lines must be devoted to the acidosis theory championed by Sir Almroth Wright. According to this writer scurvy is due primarily to an excess of acid compared with alkaline food.5 A theory of this nature was open to verification, and soon collapsed when put to the test. It was found, in the first place, that an addition of alkali was unable to cure experimental scurvy. It may be added that we have found it of no value in infantile scurvy. Holst and Froelich pointed out that potatoes and peas, two excellent antiscorbutic vegetables, have an alkaline and not an acid ash; that adding hydrochloric acid to dandelion juice improves rather than diminishes its potency; that 1 g. of cabbage, which suffices to protect a guinea-pig from scurvy, does not contain sufficient alkali to neutralize an acid state; and, finally, that scurvy is not encountered in the well-established acidosis of diabetes.
Let us turn to some of the current theories of the etiology of scurvy. For years many have held to the toxic theory, believing that poisons either were consumed in the food or formed in the intestine by means of bacterial action. At present this view is held by the minority. The situation in this respect may be compared to that of beriberi, about which there is also no consensus of opinion, a minority attributing it to the action of an unknown toxin.
A consideration of the clinical course of scurvy sheds but little light on this aspect, and can be interpreted as well for as against the action of a toxin. The nervous system, which is well known to be particularly vulnerable to toxins, is but slightly affected-the cardiorespiratory phenomena (indicating an involvement of the pneumogastric nerves), the occasional changes in the optic disks, and the abnormality of the tendon reflexes constitute the aggregate. In a general way it may be stated that the symptoms resemble those brought about by poisons of various kinds-the cottonseed poisoning in swine, the toxic products of the wheat embryo, or even mercurial poisoning in man.6 The nervous symptoms, especially the irritability of the heart, remind one of the enterogenous intoxication or enterotoxic polyneuritis described by Von Noorden. Such analogies are interesting and suggestive, but can be accorded little weight in deciding the question at issue.
If a toxin is to be regarded as the proximate cause of infantile scurvy, the question naturally arises as to the nature of the toxin. Is it exogenous or endogenous? There is sound basis for believing that the hypothetical poison is not introduced preformed in the food. In the first place, infantile scurvy frequently develops in babies who receive milk of the very best grade indeed, in contradistinction to rickets, this is not preëminently a disease of the poor. Furthermore, there is no relation between the concentration of the food mixture and its liability to induce scurvy. For example, if among a large number of infants receiving pasteurized milk from a common source, some are given the milk diluted by one-half, others given it diluted by one-third, and still others whole milk, the last group will show the least tendency to scurvy, which we should not expect were the poison contained in the food. Nor is it at all uncommon to encounter scurvy in an infant which has been fed with a very dilute milk mixture. Another side of this question should, however, be mentioned-stale pasteurized milk is more apt to produce scurvy than the freshly pasteurized, but here again the injury is in inverse ratio rather than in direct ratio to the amount consumed. There are reports of adult scurvy having been occasioned by decomposed food, such as Torup's investigation of Nansen's polar expedition, but the diet had not been faultless in other respects. The experiments of Jackson and Harley, who produced scurvy in monkeys by feeding tainted tinned meat, cannot be unreservedly accepted, as they are substantiated by no pathological examination of the bones, and the diarrhoa and the blood and mucus in the stools do not suggest simple scurvy.
Of those who held to the toxic origin of scurvy the majority had in mind an endogenous toxin, although the conception of the nature of this poison varied greatly. The minority report of the American Pediatric Society states that "scurvy appears to be a chronic ptomaine poisoning due to the absorption of toxins." Neumann considered scurvy a chronic poisoning, formed probably from the albumin of the milk, and considered the fact that the infant refused to take the harmful food as weighty evidence of its toxic nature. Kohlbrugge included scurvy in his group of "fermentive diseases," due to the overgrowth of harmful bacteria in the intestine, which are normally restrained by the acid reaction of the chyme. McCollum and Pitz, on the basis of a study of experimental scurvy, suggested that as the result of a break in the metabolism it might be due to the retention of fæces and consequent absorption of toxins. Still more recently Gerstenberger suggested that as the result of the break in the metabolism of carbohydrates, a defunctioning substance, possibly oxalic acid, is produced, which has a strong affinity for calcium.
It is of no avail to discuss these various hypotheses-the formation of intestinal toxins-except where they are based on observations which can be tested and controlled. This is true solely of the relation of constipation to scurvy, and we shall confine ourselves therefore to a consideration of this aspect of the question.
There can be no question whether retention of fæces of itself can bring about scurvy; this is excluded by the marked instances of constipation frequently encountered among thriving babies. The majority of bottle-fed babies and a large number of the breast-fed suffer from a greater or less degree of constipation. On looking over our records of infantile scurvy from this point of view, and comparing them with non-scorbutic infants, we have not been able to note a characteristic distinction. Some of the infants had normal stools, others suffered from constipation, while the records of a great number showed occasional loose stools. Furthermore, in cases of latent or subacute infantile scurvy, it was of no moment whether a laxative was given or whether constipation was induced by means of opium. The report of the American Pediatric Society shows that the majority have had a similar experience; the bowels were regular in seventy-four instances, irregular in fifteen, constipated in one hundred and twenty-six, and diarrhoal in seventy-seven. In this connection, it may be pointed out that the preparation termed "malt soup," the diet which in our experience has been most frequently associated with scurvy, is essentially laxative, and, on the other hand, that one of the most potent antiscorbutics is potato, which has no definite laxative property. It may be added, as noted elsewhere, that scurvy developed in infants in spite of their receiving cod liver oil or olive oil for long periods. It is evident, therefore, that the retention of fæces is not the essential factor in the etiology of scurvy. Its secondary rôle, especially after scurvy has developed, will be considered later in this chapter.
TABLE 1
Fecal Flora of Scorbutic...
