Scurvy, Past and Present

by Alfred F. Hess

Pathogenesis of Guinea-pig Scurvy.—From a pathogenetic point of view guinea-pig scurvy and human scurvy show remarkable points in common. Any diet that leads to the development of scurvy in man likewise brings it about in the guinea-pig, and contrariwise, any food which cures the disorder has the same beneficent effect on both species. This similarity extends so far that, as will be shown in the chapter on antiscorbutics, the relative potency of the various foods is approximately the same for man and for the guinea-pig. The parallelism generally is striking. The dietary which has been commonly employed in experimental scurvy has been that first suggested by Holst and Froelich, namely, oats, hay and water. Recently, however, this dietary has been enlarged in order to make it more complete, so as to include adequate protein, water-soluble and fat-soluble vitamine, and inorganic salts. To this end the group of workers at the Lister Institute (Chick and co-workers, Harden and Zilva) place their animals on a basal diet of one part of crushed oats and two of wheaten bran, and a daily ration of 50 to 60 c.c. of milk autoclaved for one hour at 120° C. This milk still retains a small amount of antiscorbutic vitamine. Cohen and Mendel have employed, apparently with good result, a “soy bean cracker,” containing soy bean flour which has been heated for 30 minutes at 15 pounds’ pressure (120° C.), 3 per cent. of sodium chloride, the same percentage of calcium lactate and of dried brewers’ yeast, and raw milk sufficient to supply 5 per cent. of butter-fat.

The use of raw milk was introduced by Jackson and Moore, and adopted by McCollum and Pitz and again by Pitz in a series of interesting experiments. The milk was given ad libitum. The results of these investigations were puzzling at first, until it was shown by Chick, Hume and Skelton that the dietary on which they were based contained a fundamental error which accounted for their lack of consistence. Although milk is not rich in the antiscorbutic factor, it possesses it in moderate degree, so that the outcome will be quite different according to whether a guinea-pig takes, for example, 50 c.c. or 100 c.c. daily. It is quite evident, therefore, that a food of this kind cannot be offered ad libitum, and that if this rule is not observed, most disconcerting results will follow.[36] This basic error in framing the dietary has made it impossible to accept the deductions of these authors. The conclusions of McCollum and Pitz are so striking and have led to such wide discussion, that they require consideration, in spite of the fact that the error in the dietary is now recognized. These authors found that the cæcum of their animals was greatly distended with putrefying fæces. As the cæcum is extraordinarily large and delicate in this species, they drew the deduction that the development of scurvy in the guinea-pig was due principally to the retention of fæces. “An impacted cæcum, the seat of putrefaction, may cause injury to the cæcal wall, sufficient to permit the invasion of the tissues by bacteria, or the animals may perhaps be injured primarily by the absorption of toxic products of bacterial origin.” Accessory dietary factors or vitamines, according to this theory, are supposed to play no part in the disorder, and antiscorbutics, such as orange juice, are considered to owe their efficacy mainly to their laxative properties, and to be replaceable by other laxatives such as phenolphthalein or oleum petrolatum. The efficacy of orange juice is supposed to be due to its content of citrates, and to be replaceable by what was termed “artificial orange juice,” a mixture composed of the various salts, citric acid and sucrose, in the proportions in which they are found in the natural juice.

These reports stimulated renewed interest in experimental scurvy, suggesting new aspects, and therefore directing attention to points requiring investigation. There were no data at hand on the consistency of the contents of the bowel in guinea-pigs, so that it was necessary to make appropriate observations in normal and in scorbutic animals. It was soon reported by various workers, Rappleye, Cohen and Mendel, Hess and Unger, and others, that there was no definite relationship between the occurrence of scurvy and impaction of the cæcum. In [Fig. 8] we see portrayed the stool output of a guinea-pig during the period in which it was developing scurvy, and during a subsequent period when it was being cured by means of orange juice. It is clear that there was no significant variation in the output during these divergent periods. A similar conclusion was arrived at by those who examined the cæcums of animals postmortem. Cohen and Mendel write: “Summarizing our experience with nearly one hundred scorbutic animals, we conclude that actual impaction of the fæces in the cæcum occurred in about one-quarter of the cases, and visible damage to wall, i.e., congestion or hemorrhage, or impaction, or both, was found in perhaps half of the cases. It should be noted that this statement covers all the diets we have tried.” We concur in this conclusion. Not infrequently we found the cæcums of markedly scorbutic pigs to contain semi-fluid fæces, the consistency of its contents depending on the character of the diet, quite apart from its adequacy and lack of the antiscorbutic factor. For example, a diet rich in milk, containing 100 c.c. or more, led to the formation of rather solid fæces; if oats were added to the milk diet the fæces in the cæcum were found to be still more solid, and this portion of the gut more often impacted. This condition could be detected by palpation even during life. Just as we encountered scorbutic animals on an oat, hay and water diet, who had semi-fluid fæces in the cæcums, so we met with others which were on a milk diet, and showed no signs of scurvy, although their cæcums were impacted with fæces of a putty-like consistence. Guinea-pigs do not seem to be able to tolerate a diet containing a large quantity of the fat of cow’s milk. Such a diet leads to impaction of the large intestine resulting in death, but does not induce scurvy. Jackson and Moore produced a condition of this kind by feeding pigs with cream containing 26 to 28 per cent. fat. “In every case,” they write, “the large intestine was distended with light mustard-colored semi-solid fæces.” This pathological condition is not understood, but is quite distinct from scurvy, and remarkable in view of the fact that the milk of the guinea-pig contains as high as 25 per cent. of fat. It is an interesting illustration of the marked biological difference in the butter-fat of various species.

Fig. 8.—Shows a period with the development of scurvy, and one where it was cured by giving orange juice. It will be noted that there was no marked constipation while the animal had scurvy. During a period of a few days the amount of stool was scanty, corresponding to the decreased intake of oats and hay on the days preceding. Broken line represents clinical course of scurvy.

Nor was it found, as McCollum and Pitz claimed, that antiscorbutics were replaceable by laxatives in the diet. Without entering into the details of this aspect of the subject, which will be considered in the chapter on symptomatology, it may be stated that attempts to prevent the occurrence of scurvy or to cure it by means of laxatives invariably failed. Chick, Hume and Skelton, as well as Hess and Unger, gave oleum petrolatum to a series of pigs without the slightest favorable effect. Hart, Steenbock and Smith recently reported that they had administered 1 c.c. of this oil on alternate days to one series of pigs, and 2 mg. of phenolphthalein on alternate days to another series, without relieving the scurvy. Cohen and Mendel, in order to test the adequacy of their diet as to roughage, supplemented it with additions of considerable filter paper and sawdust, “without averting the appearance of scurvy.” It is evident, therefore, that constipation does not play an essential rôle in the pathogenesis of scurvy in the guinea-pig, and that antiscorbutics are by no means synonymous or interchangeable with laxatives. These results accord with observations on infantile scurvy.

The Pathology.—The pathology of guinea-pig scurvy is essentially that of human scurvy. Hemorrhages and separations of the epiphyses or fractures of the long bones dominate the macroscopic picture. The hemorrhages are found rarely in the gums, but are common about the joints, in the muscles of the jaw or in those of the hind legs. They may be subcutaneous and appear as bluish discolorations at various parts of the body, especially if the disorder has resulted in death or if infection has been superadded. On stripping the skin we often note hemorrhages in the intercostal muscles, and beading of the ribs at the site of the costochondral junctions, least marked in the upper and in the floating ribs. This has been frequently described in connection with guinea-pig scurvy; its similarity to the rosary of human rickets has been drawn attention to recently by Jackson and Moore. It should not be regarded as “pseudo-rhachitic,” but as typically scorbutic, from a microscopic as well as a macroscopic viewpoint. On closer examination a yellowish-white transverse line may be seen at the epiphyseal junction of the ribs, and frequently some subperiosteal hemorrhage. Beading of this character has been reported by Ingier also in the “snuffles” of hogs and as the result of trauma. A similar enlargement of the chondral junctions of the sternum may be found on examining its posterior surface.

The joints of the body always show some changes. The epiphyses are enlarged to a variable degree, resembling the epiphyses typical of human rickets. As in infants, this change is met with most commonly at the wrist joint, involving the ulna and the radius. The knee-joint is likewise often involved, especially the ends of the tibia; the elbow, ankle, and the shoulder may also show an articular swelling of the bones. About these joints hemorrhages in the subcutaneous tissues may be seen, or edema extending along the extremities. Not infrequently a fracture of one of the long bones is found, which may or may not have been diagnosed during life. The common site of fracture is the lower part of the tibia or fibula. Much more frequent than fractures are separations of the epiphyses, which long since have been recognized as typical of infantile scurvy. Even gentle handling in the course of performing the necropsy may occasion a lesion of this kind—of the tibia at the knee, of the radius or ulna at the wrist, or indeed at any of the epiphyseal junctions. The infracted ends occasionally may be seen held insecurely by a delicate band of periosteum. The shafts of the bones are brittle, rarefied, and easily broken.

On opening the chest, slight hemorrhages may be noted in the pericardium and in the visceral and costal pleuræ. The heart is frequently enlarged, and the pericardial sac contains an excess of serum; the right ventricle, however, is not found disproportionately hypertrophied. Pneumonia is met with very frequently and constitutes a common terminal infection.

On opening the abdomen we may note subperitoneal hemorrhages of the muscular wall or of the coils of intestine. The liver and spleen are generally normal, as is the pancreas. The kidney frequently shows minute hemorrhages beneath the capsule and on section.