Weight curve of scorbutic baby. Effect of alkalization of milkFig. 2.—Human scurvy: weight curve of a baby that developed scurvy on a diet of malt soup (period 1). During period 2 the flour and malt soup were omitted from the diet, the same amount of milk and potassium carbonate being continued. The disorder did not abate. The only change in period 3 was a discontinuation of the potassium carbonate. This brought about a gain in weight and cure, showing the destructive effect of the alkali on the vitamine.
A test of this kind once more raises the question whether carbohydrates lead to the development of scurvy. As previously stated, there are many who believe that the carbohydrates, especially starch, have this harmful effect by requiring a large amount of the various vitamines for their metabolism. This relationship was first brought forward by Bradden and Cooper in regard to beriberi. It is a suggestion which cannot be disregarded in view of the great amount of scurvy which comes about on diets rich in carbohydrates, especially those containing malt sugar. We do not believe, however, that the harmful effect which this foodstuff exerts can be explained on the above hypothesis, as experience has shown that infants may receive for many months equally large amounts of carbohydrates—cane sugar, flour, or a combination of both—and nevertheless not manifest a similar tendency to develop scurvy.
Age Incidence.—Scurvy may occur at any age if thediet does not furnish sufficient antiscorbutic factors. As a matter of fact, it is encountered most often among infants and adults, not because these two age-groups are particularly susceptible, but because there are peculiar attendant circumstances. In the case of the infant, it is due to the fact that for almost the entire first year of its life it is dependent entirely upon milk, a foodstuff poor in antiscorbutic vitamine, and containing, under favorable conditions, barely enough to meet its requirement. If, therefore, the potency of the milk is weakened, or if an insufficient quantity is fed, and more particularly when both of these factors are involved, a scorbutic condition will ensue. The reason why older children, those over one and a half or two years of age, do not develop scurvy is largely due to their varied and liberal diet, which is amply provided by the mother or guardian, so that even in times of want they receive more than their due share of the available food supply.17
From a clinical standpoint scurvy may be said to occur in infants during the second half year of their lives. There is general agreement on this point; it is borne out by the investigation of the American Pediatric Society and by the statistics of various individuals. On the basis of a large experience, Still states that nearly eighty per cent. of the cases appear between the ages of six and ten months,and that in no case did the disorder occur before the age of five months. It is of importance from both the etiologic and the therapeutic standpoint to distinguish clearly between the age when infantile scurvy is commonly diagnosed, and the earlier stage when it appears as a general nutritional disorder. We must remember that scurvy generally takes from six to nine months to become manifest, this developmental period varying mainly in proportion to the degree of the dietary deficiency. It is evident, therefore, that there must be a prolonged period of nutritional failure which precedes the diagnosis. This stage consists of two early phases, the first months where the faulty diet causes no apparent change and seems to have no deleterious effect on the infant, and the second, of latent and subacute scurvy. The “latent” condition is one merely of unsatisfactory nutrition and retarded growth, which it is not possible to interpret; “subacute scurvy,” which develops subsequently, is distinguished by characteristic signs and symptoms. We shall not review their symptomatology, as it is given in the chapter devoted to this topic. The subject is brought forward in this connection to emphasize the fact that the scorbutic condition occurs far earlier than is generally realized, and furthermore, that if the earlier and more subtle symptoms of scurvy were comprehended, the age incidence would fall earlier than the current figures indicate. The earliest instance of this disorder which we have seen occurred in a baby four and a half months of age.
Age does not seem to play a definite rôle in regard to the incidence among adults. Scurvy frequently has been encountered among old men, and is of common occurrence among the most vigorous of the nation, the young soldiers and sailors. Some have stated that it takes placeless often among soldiers in the twenties than among those in the thirties, but this has not been demonstrated. The fewest cases have been reported among children over two years of age. It was due to the apparent immunity of this age-group that, until very recently, German writers doubted the identity of infantile and adult scurvy. The exclusion of children of this age is merely fortuitous and, moreover, is by no means absolute. One of the earliest cases of scurvy in children, reported by Montfalcon, occurred in a child six years old. Bateman in America described a case in a child of about this age. Barlow, in one of his first articles, reported scurvy in a small group of older children. The case so frequently quoted by German authors in this connection is that of Fraenkel, who described both clinically and pathologically a case of scurvy in a boy eight years of age. These cases by no means exhaust the number which are reported. Recently, Tobler has given us an account of scurvy, occurring during the war, in a Viennese foundling asylum which harbored children between the ages of two and fourteen.
Season and Climate.—Many of the older writers laid great stress on the influence of season on the occurrence of scurvy, which they believed broke out particularly in the cold and damp months of the fall, winter and early spring. It is true that most of the epidemics have occurred at these seasons of the year. This is merely what should be expected, considering that the disease depends mainly upon the supply of fresh fruits and vegetables. Where conditions are abnormal, as in war, there have been notable exceptions to this seasonal incidence. In the “Report of the War of the Rebellion” there is an instructive graph illustrating the occurrence of scurvy in our Civil War and in the Crimean War, which shows that thisdisease prevailed to the greatest extent during the winter months in the former, whereas in Crimea, the season of greatest frequency was the summer time. One of the severest outbreaks of scurvy on record is that which occurred at the siege of Thorn in Germany in the year 1703. During the months of July and August, when the weather was excessively hot, scurvy ravaged the besieged army. There are, furthermore, many reports of scurvy in the tropics during the dry season. In the island of Aruba, in the Dutch West Indies, which has been visited by scurvy year after year, and which is referred to elsewhere, the disease is endemic during the dry, hot season. Formerly it broke out on the men-of-war and vessels of the mercantile marine while they were in southern waters. As regards infantile scurvy, it has always seemed to us that season played a slight rôle; that cases which occurred in the summer tended to be less severe and to be characterized by periods of intermission rarely observed in the winter time.
The effect ofclimatehas been accorded a variable place in the etiology of scurvy. Lind believed that a damp, cold climate, such as that of the Low Countries, was conducive to scurvy. On the other hand, since it is realized that diet is the essential element, all other factors have been regarded as of no moment whatsoever. It is difficult to pass judgment on this question, since scurvy is now endemic in such a limited area of the world. It seems quite possible that a damp, cold climate, which depresses the various functions of the body, may exert an influence where the quota of antiscorbutic foodstuff is not quite adequate. Exposure to infection is also greater under such climatic conditions.
Economic status has to be considered in connection with infantile scurvy. Numerous writers have drawn attention to the fact that scurvy is seen relatively more frequently among the infants of the well-to-do and the rich than among those of the poor. This curious and paradoxical situation is due to the zealous care which the former receive—the extreme precautions in sterilizing the milk, the addition to the formulas of expensive proprietary foods, the watchfulness to avoid the child’s obtaining a chance bit of fruit or vegetable. Since the popularization of commercially-pasteurized milk in the larger municipalities, and the advertising propaganda for the sale of “baby foods” which has extended their use among the masses, this distinction in the social status has been largely obliterated.
Sex seems to play no part in the etiology of scurvy. Several writers have claimed, however, that there is a certain degree of racial immunity. For example, Sheppard reports that the Zhob Kakai seldom develops scurvy, although he naturally excludes vegetables from his diet, and Boerich noted among the prisoners of war that the Slavs, especially the White Russians, were more susceptible.18Of course a lack of susceptibility of this nature can be merely relative. Such a racial distinction may seem far-fetched, but if we admit that disposition and habits of life can play a rôle, it is quite possible for races to vary in their predisposition to this disorder. Moreover, we shall see that individuals differ markedly in this respect. Lind and others repeatedly emphasize the fact thatthe indolent and slothful sailor was stricken with scurvy far oftener than the one who was active, and claimed that physical exercise even tended to bring about a cure.19Those who have had a large experience with scurvy in adults are almost unanimous in believing that apsychic elemententers into its etiology. In this way, in a measure, they account for the frequency of scurvy among defeated troops, in besieged armies, and among men depressed by homesickness, fatigue, and discouragement. This point of view cannot be lightly disregarded, bearing in mind that depressed mental states alter the functions of the organs and markedly affect secretion. The many cases and epidemics in institutions for the insane cannot, however, be attributed to this cause, but are probably almost entirely due to a want of supervision of the dietary. Among infants, the question of the influence of race and of the mental state needs but little consideration.20For some time we have carefully observed the course of scurvy among happy and contented infants compared with those of an unhappy and fretful disposition; in some instances the former, although the diet was similar, seemed to develop scurvy less readily than the latter.
There can be no doubt that there ispredispositionto scurvy, as there is, probably, to every nutritional disorder. Among soldiers and sailors a certain number develop scurvy on the same ration which does not harm others. Some years ago when scurvy developed amonga group of infants fed on pasteurized milk, this idiosyncrasy was noted. The distinction, however, is rarely sharply defined. Careful clinical investigation will generally show that the infants which seem to be spared are not thriving quite normally; they are somewhat pale, and do not gain in weight as they should, and their appetite is poor. The most interesting experience of this kind is the following which is frequently cited: In a family where the first child developed scurvy, Finkelstein took the precaution, in the case of the second child, to have the milk boiled for as short a time as possible, and to begin mixed feeding early. In spite of these precautions this boy also developed scurvy. Finkelstein states that once before he had met with a similar mishap. An experience which he relates, regarding a foster-mother, an excellent nurse, who had three infants in succession develop scurvy in spite of preventive measures, is also of interest in this connection. The latter occurrence evidently cannot be attributed to hereditary or family predisposition, and serves to emphasize the inherent difficulties of the subject. v. Starck’s report of an instance where twins were fed on similar milk mixtures and one developed scurvy, whereas the other thrived satisfactorily, is a striking illustration of the rôle of idiosyncrasy. This case, as well as many others, fails to be absolutely convincing in view of the fact that the daily intake of milk is not recorded.
A predisposition to scurvy cannot be ascribed to a condition of general malnutrition. For example, among infants it has never seemed that those suffering from marasmus or atrophy were particularly prone to develop scurvy. Whether syphilis, tuberculosis or malaria tendsto precipitate the onset of this disorder cannot be stated.21In view of the fact that prematurity is such an important factor in the pathogenesis of rickets, it would be of interest to know whether a similar relationship exists between infantile scurvy and prematurity. The only clinical condition which we have found predisposing to scurvy is the “exudative diathesis” of Czerny, a term which implies a tendency to develop exudations of the skin or of the mucous membranes. Probably it is not without significance that in this diathesis the blood-vessels may evince a decided weakness, an increased permeability, as demonstrated by the “capillary resistance test.” (SeeSymptomatology.)
Nothing whatsoever is known regarding the possible influence of the fat, protein, carbohydrate and salt content of the diet on the development of scurvy. Is it entirely immaterial whether one or another food element largely predominates, or is the antiscorbutic factor to some extent modified by other components of the food? Influences of this kind, which at most are secondary, cannot be ascertained by the biologic test which at present has to be relied on to measure the development of scurvy and the potency of antiscorbutics. It is quite possible that the course of scurvy may be affected by the character of gastric and intestinal digestion, by the activity of the glands which pour their secretions into these organs, by the destruction or elimination of the antiscorbutic factor in the food. The frequent association of dysentery and scurvy noted during the recent war and referred to by many previous writers, shows the effect of intestinal disorders. These hypotheses are tentatively advanced becauseit is evident that some factor exists, apart from the mere antiscorbutic value of the diet, which at times exerts a potent influence on the development of scurvy. Cases developing in spite of a moderate amount of antiscorbutic food, and others not responding to the addition of vegetables or fruit to the diet—although not numerous—have occurred too frequently and have been reported by too experienced observers to be brusquely disregarded. For example, Neumann, one of the keenest clinical students of scurvy, stated that he had met with four instances of this nature. Hess and Fish reported two similar experiences.
The secondary etiologic factors are mainly predisposing; a few words, however, must be added concerning what may be termedexciting factors. Infection is the most important condition which may suddenly and precipitously induce scurvy. This fact was brought to our attention in 1912 in connection with the outbreak of scurvy among infants receiving pasteurized milk. Its explanation was not clear at the time, but was elucidated by subsequent experience, and was described in 1917 as follows: “Latent scurvy was prematurely changed to florid scurvy by the presence of a ward infection; an epidemic of ‘grippe’ precipitated an epidemic of scurvy exceptional in its hemorrhagic tendency.” The association of scurvy and infection has been recently emphasized by McCarrison and others, and seems to hold good for the other so-called deficiency diseases. In this connection one other exciting cause of scurvy may be mentioned, namely, trauma. The older writers noticed that following a fall or an accident, a sailor frequently developed scurvy, and Barlow in 1894 remarked on the influence of trauma in connection with infantile scurvy. As might be inferred, its effect is mainly to induce premature rupture of the weakened blood-vessels;in infants we have seen this occasioned by pressure exerted on the lower end of the thigh to ascertain the presence of tenderness. Viewing the situation broadly, it must be acknowledged that except for the realization that scurvy is due to a new food factor—a vitamine—our fundamental understanding of its pathogenesis has advanced but little, in spite of the employment of experimental methods and the availability of modern technic.
It is doubtful whether mere clinical studies will contribute in a large measure to the solution of the pathogenesis of scurvy. Much may, however, be learned by investigations of the metabolism in human scurvy—an aspect of the problem which, as will be brought out in a subsequent chapter, hardly has been explored. By this means may be acquired a clearer understanding of the effect of an antiscorbutic deficiency on the tissues and on cellular activity. Much may be expected from physiologic and pharmacologic studies of the specific vitamine, although it is not yet available in a pure state. Finally, it is probable that the solution of similar questions relating to the pathogenesis of cognate disorders—a study which is engaging the best efforts of so many workers throughout the world—will shed light on this particular disease.
We shall not discuss the subject of vitamines in general, but confine ourselves to the more limited field of the antiscorbutic vitamine. The recognition of the “accessory” dietary factors is of such recent date, however, that it will be well to consider briefly how attention came to be directed to them and how their existence was ascertained. As in the case of so many scientific discoveries, it is difficult to point to the exact time when the advance was made. On looking back we find that Lunin, in 1881, noting that mice were unable to live on a diet consisting of protein, fats, carbohydrates, salts and water, came to the conclusion “that other substances indispensable to nutrition must be present in milk besides caseinogen, fat, lactose and salts.” This work did not stimulate similar investigations, nor did Lunin, as might have been expected, allude to scurvy. The work which focussed attention on this novel aspect of dietetics was the report of Eijkman, in 1897, to the effect that when fowl are fed decorticated rice, they develop a disease resembling beriberi, and that the paralytic symptoms disappear on feeding them rice polishings or its alcoholic extract. Here, for the first time, was a positive rather than a negative experiment, and one capable of simple verification. The subject was placed on a scientific basis by the classic investigation of Hopkins, who experimented with purifiedfood substances, and demonstrated how diets which were deficient could be rendered adequate. As early as 1906 he wrote “the animal body is adjusted to live either upon plant tissues or other animals, and these contain countless substances other than the proteins, carbohydrates and fats.” “In diseases such as rickets, and particularly in scurvy, we have had for long years knowledge of a dietetic factor, but though we know how to benefit these conditions empirically, the real errors in the diet are to this day quite obscure.” The work of Osborne and Mendel, and McCollum and Davis in this country, of Schaumann, Funk, Stepp and others, all led to the conclusion that purified diets are unable to satisfy the nutritive requirements of rats or mice, and that extracts of the natural foods suffice to render the diet adequate.
The same rule holds for man, who, when deprived of these vitamines, develops the so-called deficiency diseases—typically modern disorders. Regarded as a group, they are a consequence of our altered mode of life and peculiar civilization. They follow naturally upon the development of immense cities housing millions of people, who necessarily must receive perishable foodstuffs produced at a great distance. To even a greater extent they are the product of countless ingenious methods devised mainly to render foods stable—drying, heating, the addition of preservatives—most of which accomplish their object, but incidentally rob the food of its essential vitamine.
None of the vitamines has been isolated in a pure state. The nearest approach to this desired end has been the work of Funk, who obtained the water-soluble vitamine in a state of such concentration that about 3 mg. sufficed to cure a pigeon of polyneuritis. In considering the attributes of the antiscorbutic vitamine, it must be bornein mind that this factor is referred to as it exists in various foods; for example, in orange juice or in cabbage, and furthermore, that the method of ascertaining its presence or concentration is limited to the crude biological test of animal feeding.
The antiscorbutic factor is distinguished by being the most sensitive of the three vitamines, the most unstable, the least resistant to physical or chemical processes. It may be regarded as one of the most delicate indicators of the biological integrity of foodstuffs; however, as Falk and his co-workers have shown, the enzyme property of living matter is still more readily destroyed. The antiscorbutic vitamine is soluble in water, and therefore is termed by some the “water-soluble C” factor. It is also soluble in alcohol, as shown by the experiments of Hess and Unger and of Harden and Zilva, and the therapeutic tests on infants of Freise and of Freudenberg.23It possesses, therefore, the solubility of the water-soluble vitamine. Some have suggested that it may be derived from this vitamine, others that instead of one there may be a series of antiscorbutic factors—suggestions based on pure hypothesis. Holst and Froelich showed that this vitamine passes, without appreciable loss, through dialyzing parchment, and Harden and Zilva (2) that it can pass through a porcelain filter. The latter, using the method of Seidell, demonstrated that this vitamine is not adsorbed by fine precipitates such as fuller’s earth, differing in this respect from the water-soluble vitamine; and that in a mixture of equal volumes of autolyzed yeast andorange juice, the antiscorbutic vitamine remained unaffected, whereas the water-soluble A was entirely removed.
One of the most distinctive characteristics of the antiscorbutic factor is itssensitiveness to even moderately high degrees of heat. In this respect it differs markedly from the water-soluble or so-called “antineuritic vitamine” which withstands exposure to high temperature. The reaction of the antiscorbutic vitamine in this regard is not a simple one, and cannot be expressed by a mere statement of the degree of heat and the length of exposure. Numerous other factors, especially the reaction of the medium, but also the physical environment, must be taken into consideration—for example, cabbage is more resistant to the action of heat than its juice. An understanding of the relation of antiscorbutics to heat may perhaps best be obtained by considering the subject in connection with some definite foodstuffs. The most exhaustive study from a quantitative standpoint is that of Delf. She showed that when cabbage is subjected for an hour to a temperature of 80° to 100° C., 90 per cent. of its antiscorbutic vitamine is lost, and that 80 per cent. is lost when a temperature of 90° to 100° is maintained for twenty minutes, or a temperature of 60° for a period of sixty minutes. This experiment shows that the destructive influence of heat is enhanced to a comparatively slight degree by a rise of temperature, only about threefold when it is raised from 60° C. to the boiling point. This result points to a temperature coefficient of about 1.5 to 10° C. of temperature. It is suggested by Delf that this low coefficient of destruction is opposed to the enzyme or protein-like theory of the nature of the vitamine, and suggests a simpler constitution. On the otherhand, we must bear in mind that the proteins which have been used in experiments and found to possess a high coefficient of heat, have been tested in the pure state, whereas the vitamine of the cabbage is bound up in the cell.
Experiments with this vitamine as found in milk accord with the above investigation, demonstrating that intensity of heat is not as destructive as prolonged heating. This agrees with the clinical experience that milk which has been boiled for a few minutes does not induce scurvy as readily as pasteurized milk which has been heated for 45 minutes to 140° or 165° F. (Hess and Fish).
As demonstrated by tests with orange and with lemon juice, the antiscorbutic vitamine is greatly protected from the destructive effect of heat when it is associated with an acid. This was shown first by Holst and Froelich and has been confirmed by numerous observers. An excellent example of marked thermostability conferred on a food by its acid reaction is furnished by the tomato, which is strongly antiscorbutic even after it has been subjected to the canning process. Conversely, Harden and Zilva have shown that the vitamine is destroyed by alkali even when dilute (one-fiftieth normal sodium hydrate) and kept in contact at room temperature; this alteration does not take place at once, but in the course of several hours.
It is true that the antiscorbutic factor is peculiarly sensitive todrying, but there are exceptions to this rule, so that it is incorrect to state, as does the British Report of the Medical Research Committee, that “it may be regarded as an axiom that dry or dried foodstuffs will not prevent scurvy.” We have shown that fresh milk dried by the Just-Hatmaker process may retain by far the greater moiety of its virtue. In this regard rapidity of desiccation and subsequent protection from oxidativeprocesses are important factors. The general rule holds true, however, that this vitamine, in contradistinction to the “water-soluble” vitamine, is readily damaged and destroyed by drying.
This vitamine is peculiarly sensitive toaging, especially when it is present in an alkaline or neutral medium; but even in an acid medium its potency soon diminishes. Harden and Zilva found this to be the case with lemon juice stored for a fortnight in the cold room, and our experience has been similar in regard to orange juice kept in the refrigerator under a layer of liquid petrolatum. In milk the antiscorbutic factor diminishes with age, especially following pasteurization, in the course of which most of the acid-forming bacteria have been destroyed. Aging has the least effect when the food with which the vitamine is associated has been dried. This is true not only of lemon and of orange juice as demonstrated experimentally and clinically, but even of milk, which even after it has been dried and stored for months, may still possess marked curative value.24
Experiments by Harden and Zilva showed that exposure of lemon juice toultra-violet raysfor eight hours does not influence its antiscorbutic activity, that exposure of autolyzed yeast for the same length of time likewise does not impair its “antineuritic” potency, but that under identical conditions the fat-soluble factor in butter becomes inactivated. Similar tests carried out by the author with orange juice led to the same result. It thus appears that one of the vitamines—not the most unstable—manifests a peculiar sensitiveness to a certain form of physical or chemical action.
In view of the fact thatshakingpartly destroys pepsin and rennin, as shown by Shaklee and Meltzer, it would be of interest to ascertain whether this process brings about any impairment of the antiscorbutic vitamine. Particular interest is attached to this question because it is generally recognized that milk loses some of its potency in the course of handling—whatever may be comprised by this term. In experiments on the fat-soluble vitamine Steenbock and his co-workers found that “somewhere in the course of the manipulation to which the butter fat had been subjected, factors had been introduced which were responsible for a vitamine destruction.”
Before discussing the question of the manner in which the antiscorbutic vitamine functionates, it may be well to state briefly the type of the disturbance which its deficiency occasions. The chief manifestation is damage to the integrity of the endothelium of the vessels, resulting in hemorrhage—whether from diapedesis or from rhexis or both of these conditions, the microscope does not inform us. Nor can it be stated positively that the endothelium has not been injured by a secondary toxic or bacterial factor. However this may be, the end result of the deficiency is endothelial damage, a pathologic condition which may be demonstrated clinically in scurvy by the “capillary resistance test” (chapter VII). The other marked functional alteration in scurvy is increased susceptibility to infection; but how a vitamine deficiency induces this vulnerability cannot be explained. Clinical tests show that the blood contains sufficient antitoxin (diphtheria) to afford protection. Harden and Zilva found that “guinea-pigs fed on an unrestricted mixed diet, on a quantitatively restricted mixed diet, and a scorbutic diet showed no differentiation in amboceptor and agglutinin titres, and inthe complement activity of the blood.” If this is to be interpreted as indicating that the protective substances of the body undergo but little alteration, we must consider whether susceptibility to infection, as well as tendency to hemorrhage, is not due largely to alteration in the cement substance of the endothelial and epithelial membranes.
The Mode of Action of the Vitamine.—One of the most interesting as well as puzzling questions in regard to the antiscorbutic vitamine concerns the manner in which it prevents or cures scurvy. It is a subject which at present is in a state of flux, hardly having emerged from the realm of hypothesis, so that detailed consideration will profit little. At first themodus operandiwas explained and accepted as enzyme action, but it was soon evident, in view of the thermostability of the vitamine, that it could not be classed as a ferment or enzyme in the generally-accepted sense of this term. In general, it may be stated that there are two main views: one that the vitamine acts directly, and the other that it acts indirectly through the function of the endocrine glands.Direct action, furthermore, may be accomplished in at least one of three ways. The vitamine may (1) serve as a source of nutriment for the tissues, (2) exert an antitoxic effect on toxic products, or (3) function as a catalyzer. The first interpretation is evidently the simplest and conforms to the long-established knowledge of caloric food factors. That such small amounts as 2 c.c. of orange juice daily should suffice to protect an animal from nutritional disaster runs counter, however, to former conceptions of food nutrition. Further than this there is little against this viewpoint. In its favor is the fact that, up to a certain point, antiscorbutics act in direct ratio to the amount given; for example, 2 c.c. of canned tomato juice is insufficient to prevent scurvy inguinea-pigs, 3 c.c. will protect some but not all of a series, whereas when the amount is increased to 4 c.c. daily all animals will be saved. As we are considering new food factors it is manifestly unwise to judge them by old standards, and to decide offhand that they cannot possess such a high degree of nutritive power. This question must be regarded as still open.
The antitoxic theory suffers from the fact that the toxic origin of scurvy cannot be established. Before this is possible, it is clear that it will be difficult to bring forward convincing evidence of a neutralizing substance. Against this theory is the fact that elimination therapy is of no avail in the treatment of infantile scurvy. Hess and Unger (1919) failed to alleviate the symptoms by means of catharsis, diuresis, sweating and repeated intravenous injections of normal salt solution. In its favor it may be advanced, in a general way, that the vitamine, in many characteristics, resembles an antitoxin—in its extreme lability, its destruction by heat, aging and alkalies. On the other hand, antitoxins also are readily destroyed by acid which, as has been shown, exerts a protective influence on the antiscorbutic factor. The rapidity of action of the vitamines, one of the most impressive phenomena, calls to mind the neutralizing action of an antitoxin, and probably has given rise to the analogy. Williams suggests that the vitamines have “a general, non-specific, antitoxic or eliminative action” on toxic substances resulting from the metabolic decomposition of food.
The theory has been advanced that the action of the vitamines is catalytic. Although this viewpoint has been taken regarding the water-soluble rather than the antiscorbutic vitamine, it will be well to review briefly the work on which it is based. Among the first to suggestthis hypothesis were Vedder and Clark, who noted a relationship between the amount of vitamine required by fowls and their carbohydrate intake. Funk in 1913 made a similar observation in regard to beriberi, and in the following year, with von Schoenborn, showed that a vitamine-free diet led to hyperglycæmia, with diminished amount of hepatic glycogen, and that the addition of water-soluble vitamine diminished the hyperglycæmia and increased the liver glycogen. The work of Burge and his co-workers on the catalase content of tissue led to a similar conclusion. Their results may be summarized by the statement that the oxidative processes are hampered and fail to balance the autolytic changes, and, furthermore, that a relationship exists between the catalase activity, acidosis and normal oxidative processes. This theory would presuppose that scurvy is due to the formation of toxins which are normally in process of continual destruction in the body. According to some, these catalyzed toxic substances are metabolic in character, originating from incompletely oxidized food; according to another interpretation, they are the product of autolyzed tissue cells (tissue toxins). The difficulty with this explanation is that scurvy cannot be prevented or cured by a diet containing food of high catalytic power. For example, wheat embryos which, according to recent investigations of Crocker and Harrington, have a high catalytic activity, were found of no therapeutic value in relation to infantile scurvy (Hess, 3).
This problem has been approached from quite a different angle. As is well known, certain bacteria require serum, blood, milk, etc., in order to grow satisfactorily on artificial culture media. It has been established recently, primarily by the work of Lloyd, thatthis peculiarity in the cultivation of microörganisms is due largely to their requirement of vitamine. She found a relationship of the inverse order between the amount of amino acid present in the culture medium and the amount of vitamine required to stimulate the growth of strains of meningococcus. Reasoning from this experience, she suggests that the action of the accessory growth factors is to increase the reaction velocity of the proteolytic metabolism. Here we find the vitamines once more regarded as catalyzers. This author, however, associates their activity with proteolytic rather than with carbohydrate metabolism. Interesting and suggestive work of similar nature has been carried out in relation to the growth of protozoa and of yeasts (Eddy). Investigations of this kind, dealing with unicellular organisms propagated on a simple food, have the advantage of greatly simplifying the problem.
The recent work of Dutcher falls under this caption, differing merely in the fact that he attributes to the vitamines anindirect action. He has demonstrated that the tissues of polyneuritic birds show a decrease in catalase activity to a point 56 per cent. below normal, and that this activity is largely restored when the birds are cured with vitamine. According to this writer the vitamine functions as a metabolic stimulant, and its lack results in a depression of the body oxidations with an accompanying formation of toxic metabolic products, injurious to the nervous system. The action is regarded as coming about in an indirect manner, being accomplished through the hormone action of the vitamines on one or more glands of internal secretion.
Theendocrine hypothesis, suggested by Funk in his monograph, is not without some corroborative evidence. In testing the pharmacologic action of the water-solublevitamine, Uhlmann found that it stimulated the various glands of the digestive tract, in this respect acting like pilocarpine. Some years ago Albert expressed the opinion that the action of this vitamine was “vagotropic” like atropine, and recently Dutcher has reported definite relief and cessation of polyneuritic symptoms by means of pilocarpine (0.5 mg. subcutaneously). He claims equally good results from thyroxin, the hormone of the thyroid gland, from desiccated thyroid and from tethelin (pituitary). Voegtlin and Myers conclude, as the result of experiments with brewers’ yeast, that the chemical and physical properties of secretin and vitamine are identical.
The early work of Funk and Douglas, which showed that variousglands of internal secretiondiminish in size and undergo degenerative changes when the diet is vitamine-free, the newer work of McCarrison and of Dutcher to the same effect, clearly point to an intimate relationship between some of the endocrine glands and the vitamines. As regards scurvy, the only work is that of Rondoni, McCarrison and of LaMer and Campbell on the adrenal glands, which were found by all to be enlarged in guinea-pigs suffering from this disorder. These investigations must be regarded as tentative rather than conclusive until confirmed by similar necropsy reports in man. In this connection it should be noted that thyroid, parathyroid or suprarenal extract is of no avail in the treatment of scurvy. This failure may, however, be explained by the fact that the normal balance of glandular activity was not established. We must bear in mind, however, that although the vitamines may influence the secretion of the glands of internal secretion, this explanation does not satisfactorily account for the symptoms of the “deficiency diseases.” These disorders do not in the slightest respect resemblethe clinical pictures which we are accustomed to associate with a lack of activity of the glands of internal secretion. If the polyneuritis of beriberi and the hemorrhages of scurvy are attributable to a diminished secretion of the endocrine glands, then it will be necessary to revise present conceptions of their physiologic functions.
The Fate of the Vitamine in the Body.—One of the most important questions in relation to the antiscorbutic vitamine, quite apart from its chemical nature, physiologic function, and its source, is its fate in the human body after it has reached the alimentary canal or been carried to the tissues. It can be readily appreciated that our knowledge of this aspect is very meagre. We shall endeavor, however, to detail what little is known of this subject, conscious of the fact that investigations of the next few years may contradict our present viewpoints.
Most of the constituents necessary for the construction of tissue or for carrying on its functions can be synthesized by the animal body from the basal foodstuffs. It has been ascertained within the past decade that certain constituents—for example, some amino-acids of the protein molecule—are building-stones which cannot be primarily elaborated by the cells, but must be supplied by the food. At present the vitamines—including the antiscorbutic vitamine—are included in this new and essential group of substances which the human organism cannot manufacture. Animal experiments seem to bear out this conception of the vitamine whether we regard them as dynamic or as indispensable tissue elements in the structural sense.
A closely-related but less fundamental question is that ofthe ability of man to store vitamines—whether the tissues can hoard an excess of these factors, or whether, in this respect, we are carrying on a precarious hand-to-mouthexistence in regard to cellular nutrition. It is of course clear that at all times the various organs and tissues must contain a certain amount of the vitamines. This has been shown for the water-soluble or “antineuritic vitamine” by the fact that even the organs of birds which have died of polyneuritis contain an appreciable quantity of the specific vitamine, although an insufficiency of this very factor has led to their death. That such is the case is demonstrated for the antiscorbutic vitamine by the fact that muscle tissue contains sufficient antiscorbutic to protect individuals subsisting largely on a diet of which raw meat constitutes the sole antiscorbutic agent (Stefánsson). It is very probable that some organs contain more of the vitamines than others; this has been proved for the “antineuritic” factor, and seems to hold good for the antiscorbutic—the liver being particularly rich. No quantitative study has been carried out from this point of view regarding the antiscorbutic vitamine, and it would be well worth our while to ascertain the relative antiscorbutic potency of the various organs of the body. Some time ago we undertook experiments to determine whether the guinea-pig is capable of storing this vitamine. One series of guinea-pigs was fed daily 6 c.c. of orange juice for a period of two weeks, whereas another series, of about the same weight, was given, in addition to the basal ration, only 3 c.c. per capita (the minimal protective dose). After this preliminary period both series were placed on a diet containing practically no antiscorbutic. Both groups came down with scurvy after about the same interval, leading to the conclusion that there could have been little if any storing of the excess vitamine by those which received twice the “minimal protective dose.” The experiments of Harden and Zilva, who fed aconcentrated lemon juice, showed that this potent agent also was unable to provide against a subsequent period of antiscorbutic deficiency. It should be realized that the results of these tests on guinea-pigs cannot be applied to man without tests on other species.
It might be thought thatthe blood—the purveyor of the vitamines to the tissues—would be particularly rich in these essential factors. Such, however, was not our experience in respect to the antiscorbutic vitamine. The blood possibly varies greatly in this respect according to the diet of the individual, or even according to the interval elapsing after the ingestion of antiscorbutic food. Our opinion is based on the surprisingly poor therapeutic effect of blood transfusion in the treatment of scurvy. To illustrate: An infant weighing about fifteen pounds received six intravenous injections of citrated blood—one of 200 c.c., given by the direct method, and a month later five smaller transfusions with citrated blood, which aggregated 205 c.c.25In spite of this addition of blood, the hemorrhage and congestion of the gums did not disappear, nor the general condition improve, as would have happened had 50 or 75 c.c. of orange juice been given by mouth. It seems probable that small quantities of vitamine are being transmitted at all times by the blood and supplied to the cells, but that its normal content of this factor is not great. The antiscorbutic potency of blood may perhaps be compared to that of milk. Animal investigation may show that various vessels—for example, those supplying or draining certain glandular organs—differ in the antiscorbutic quality of the blood which theycarry. It is evident, therefore, that many transitory factors may influence the vitamine content of the blood, and that—as in the case of milk and fruits and vegetables—we are not dealing with a constant and unvarying agent.
Nothing whatsoever is known concerning theexcretionof the antiscorbutic vitamine. No attempts have been made to recover it from the urine, or to ascertain if, when large amounts are ingested, the excess is thrown off by the body. This suggests the question—a corollary of that raised in connection with the vitamine content of the blood—whether it is immaterial if the vitamine is taken frequently in small amounts, or is provided only occasionally and at longer intervals in larger amounts. Is it of no moment whether the infant receive its quota of antiscorbutic every few hours through the medium of the breast milk, or only once a day in the form of orange juice or tomato? If we turn to studies on the other vitamines for enlightenment as to the possibility of excretion, we find that Muckenfuss recovered the water-soluble factor from ox bile and from human urine.26In this article he proposes the interesting question of a possible variation in the vitamine output under pathological conditions, which may be responsible for the development of functional disturbances in children.
It would be of interest to know thefate of the antiscorbutic vitamine in the gastro-intestinal tract. How is it affected by a lack of the acid gastric juice, or by the alkaline intestinal secretions, or by the bacteria in the lumen of the gut? From which part of theintestine is it largely absorbed? May an appreciable amount undergo destruction before this is accomplished? None of these questions can be answered satisfactorily in the present state of our knowledge, but they suggest that the mere fact that an adequate quota of antiscorbutic vitamine is provided in the food does not necessarily insure an adequate supply for the tissues. If in addition to the question of intake we must take into account that the vitamines may suffer various vicissitudes, it may come to pass that pathological conditions at times destroy or render them partially inactive. In this way we may account for irregularities in the clinical course of disorders associated with vitamine deficiency.
Of prime importance, however, is the effect of the vitamineson the glands of the alimentary tract and on the digestive processes. A diminution of gastric juice, or in some instances a total absence, has been observed in adult scurvy, and noted by us in two cases of infantile scurvy. As mentioned elsewhere, some consider the function of the water-soluble vitamine analogous to that of secretin. In applying this hypothesis to scurvy it must be borne in mind that the sequence may be reversed, that the lack of vitamine may not lead to the gastric achylia, but that the achylia may come about secondarily as the result of the malnutrition.
We have referred to“irregularities” in the course of the “deficiency diseases.”A careful perusal of the literature leaves one with the impression that the most experienced observers are not entirely satisfied with the exclusively etiologic relationship of the vitamine to its respective nutritional disorder. In regard to scurvy, more particularly, there are numerous scattered reports where the disorder did not yield to antiscorbutic foods as mighthave been expected, or where, on the other hand, it suddenly and inexplicably retrogressed, although there had been no alteration in the dietary.27These instances are not common, but they occur from time to time, and their occurrence must be accounted for. In relation to beriberi and avian polyneuritis improvement of this kind has frequently been explained on the theory of a sudden mobilization of vitamines from the tissues. There is, however, no data on which to base such explanations, and it may be that a lack of parallelism between vitamine intake and the clinical course may be due at times to processes taking place in the alimentary tract.
The fat-soluble vitamine has been termed by some the growth vitamine. All the vitamines, however, are closely associated with the function of growth, which their deficiency tends to inhibit. In the chapter on symptomatology, it will be pointed out that infants suffering from scurvy fail to grow normally both in length and in weight. To a certain extent this may be due to a loss of appetite, which is one of the characteristic phenomena accompanying the scorbutic condition. On the other hand, this anorexia may be secondary and not primary to the impairment of the growth impulse, which may lead to a dysfunction of various body processes.
It is of little value to look ahead and try to foresee what the next decade will bring forth in regard to the nature of the vitamines. Investigation has broadened remarkably during the past few years and now embraces the chemical field—chemical and adsorption methods, thelarge realm of biology, including studies in physiology and pharmacology; and recently pathology has once more been called upon to aid in the solution of the problem. Probably additional vitamines will be discovered. From time to time it has been suggested that a specific growth vitamine exists quite distinct from the three which are recognized, and recently Mellanby has suggested still another food factor—a specific “rachitic vitamine.” When we reflect that the characteristic functions of the various organs—the kidneys, liver, etc.—must depend on essential differences in chemical structure, the complexity of the entire problem of unidentified factors becomes evident.28
Physicians have had a general knowledge of the pathology of scurvy for a great many years. Lind, in his “Treatise on the Scurvy,” published in 1772, included a chapter on “dissections” and a postscript on “Appearances on Dissections of Scorbutic Bodies,” based on a large, although indefinite, number of postmortem examinations. In the century which followed, there are to be found many reports of scurvy, especially in connection with the frequent wars, but it is surprising how little detailed pathologic information they furnish. Barlow’s publication in 1883, establishing the identity of the scurvy of adults and of infants, must be regarded as the modern milestone in the study of the pathology of this disorder. This work did not contribute richly to the data of the subject, or suggest novel interpretations, but directed attention to a new source of material—the increasing number of cases of infantile scurvy—at a critical moment when the opportunity for the study of scurvy in the adult was rapidly becoming less. At the time of Barlow’s exposition of the true nature of “acute rickets,” scientific medicine was concentrating its interest on pathology. Tissues were being carefully studied by means of the microscope, and scurvy was subjected to this new method of investigation. As a result of intensive application of this technic, a lesion of the bones was identified and established as characteristic of scurvy. Study was focussed so exclusively on the bones, that for many years, indeed until very recently, the other organs of the body were neglected.This is true of the gross as well as of the microscopic anatomy. Protocol after protocol gives a hasty account of the appearance of the various organs, merely as a routine introduction to a careful and often minute study of the bones (Table 2). As the result of this myopic vision,enlargement of the heart, for example, which should have been noted many years ago, was, until recently, unobserved—indeed, the heart is but occasionally mentioned in the protocols.
TABLE 2
A new era in the pathology of scurvy was inaugurated by the availability of experimental scurvy and also by the stimulation occasioned by the recent conception of vitamines and the so-called deficiency diseases. In endeavoring to elucidate this fascinating problem, it has gradually been realized that pathology may be of service—for example, in relation to the involvement of the endocrine glands. Accordingly, studies of the minute pathology of the various organs have been undertaken in many laboratories throughout the world (Italy, India, England, Germany and the United States). An additional stimulus to investigation in pathology has been furnished by the recent war, which, as shown elsewhere, led to a great increase in scurvy among both the military and civilian population. The excellent report of Aschoff and Koch from Roumania was made possible by this catastrophe, and will no doubt soon be followed by others of similar character.
Gross Pathology.—General Appearance.—The skin usually is pale, livid, and dotted with numerous petechiæ. These vary in size from the tiniest pin-points, barely recognizable to the naked eye, to ecchymoses of moderately large size. The most frequent site is the lower extremities. The trunk is always less affected, hemorrhages tending to occur along the mid-line and especially around the umbilicus. There may be also larger superficial hemorrhages, showing great differences in color, from the redder tone of the more recent, to the blues, browns and greens of the older lesions. Bleeding from the noseand mouth is not uncommon in fatal scurvy, and occasionally exophthalmos is present, usually unilateral, and due to subperiosteal hemorrhage of the orbital plate of the frontal bone. Rigor mortis is generally slight, and, according to Lind and to von Opitz, decomposition takes place rapidly.
There may be great emaciation, especially where secondary infection has supervened. General wasting occurs, however, in uncomplicated scurvy due to starvation—the result of lack of appetite or a deficiency of the general food supply. Children, especially infants, are undersized, as illustrated in treating of the symptomatology, and their bones may be decidedly smaller than normal. Generally there is someedemaabout the ankles, and in children a somewhat characteristic puffiness about the eyes. General anasarca also occurs, in some cases associated with renal involvement. Peculiar boggy, “tumor-like” masses of localized edema may be present, which were considered by the earlier writers (Lind) to be one of the typical lesions of this condition.
Hemorrhages.—Hemorrhage is such a striking manifestation that it is not surprising to find it was regarded by the older writers as the pathognomonic sign of scurvy. The bleeding may take place into almost any organ, and vary from small petechiæ to very extensive extravasations. The hair follicles and sweat glands are particularly susceptible, as Lasèque and Legroux noticed in cases occurring in the French prisons. Aschoff and Koch, during the recent war, noted the same peculiarity of involvement, calling attention also to the fact that previous skin diseases such as keratosis or seborrhea seemed to predispose to this localization.
Trauma plays a very important rôle in determiningthe location of the deeper as well as of the superficial hemorrhages. In adults, especially in soldiers, in whom the greater number of cases have been recorded, the lower extremity is the commonest site, between the knee and ankle, the area most exposed to blows as well as acted upon by static congestion. In infants, the inner aspect of the thighs is a frequent site due to the trauma of the diaper.
The most characteristic hemorrhage, the subperiosteal, will be fully discussed when considering the bone lesions. The deeper hemorrhages may be very extensive. They tend to follow the connective-tissue strata, and in the muscles are usually limited by the muscle sheaths. The blood surrounds the muscle fibres, which appear quite intact. The neighboring blood-vessels are congested and may contain thrombi, both venous and arterial. Such thrombi are found also in areas where extravasation has not taken place, and conversely, hemorrhages occur where no thrombi are demonstrable, so that a mutual causal relationship cannot be proved. Further evidence in regard to the mechanism of these extravasations is presented in the discussion of the minute anatomy. Brownish pigment, undoubtedly derived from the blood, is frequently found in the neighborhood of the hemorrhagic areas. New connective tissue also grows in these areas, so that in healing cases a marked formation of scar tissue will be found. Bizarre forms of hemorrhage at times have given rise to confusion in diagnosis; hemorrhage involving the right lower abdominal quadrant may simulate appendicitis; when occurring in the region of the transverse colon it has been mistaken for an epigastric new-growth.
Certain parts of the body seem less predisposed tohemorrhage. The central nervous system is often spared, notwithstanding extensive bleeding elsewhere, the meninges being somewhat more frequently involved. Hemorrhage of the lungs is also less common than might be expected, and it is probably true as Lasèque and Legroux suggested, that previous pulmonary disease, particularly tuberculosis, is an important predisposing factor.
Anasarca.—This comprises the second characteristic lesion found in scurvy at necropsy and was referred to in the earliest records of the disease. In the account of his dissections Lind writes: “The breast, belly and several other parts of the body were filled with this water or serum,” mentioning also the pericardium and ventricles of the brain. He also noted that all the tissues seemed to contain an excessive amount of fluid, a condition which may be so striking that the muscles appear bathed in serum. In one of his first cases with postmortem verification, Barlow described this appearance as follows: “The muscular walls of the thorax were pale yellow and watery, as though they had been bathed in serum.” In many cases this edema is most marked in the neighborhood of the hemorrhages, for example, in the muscles of the thigh when subperiosteal hemorrhage has taken place; less frequently it is produced by venous thrombosis.
Any or all of the serous cavities may be involved in this hydrops, the order of frequency being pericardium, pleuræ, peritoneum, and joint surfaces, especially the knee. The fluid is clear and straw-colored, or, in the event of secondary infection, becomes cloudy and fibrino-purulent. Later the exudate may become organized so that the entire cavity is filled with a solid mass, which binds the organs together and obliterates the cavity. The exudatemay be blood-stained or apparently consist entirely of clotted blood.
Heart.—In the protocols of most necropsies, the heart is passed over with scant mention. For example, Lind’s only statement in this regard is that “all those who died suddenly, without any visible cause of their death, had the auricles of their heart as big as one’s fist, and full of coagulated blood.” Barlow accords it no attention, nor do most of the writers who immediately followed him. The first careful description of the heart is to be found in the excellent work of Schoedel and Nauwerk, which contains the following record in regard to three of the five necropsies on infantile scurvy: (1) Pericardial fluid somewhat increased, both ventricles moderately dilated, the right somewhat hypertrophic. (2) The heart showed a hypertrophy of the right and left ventricles, as well as dilatation of the right ventricle. (3) The right ventricle is dilated and slightly hypertrophied, the muscles pale and tough. There is no word of comment relative to these cardiac changes, which evidently were considered fortuitous. The same observation holds true in regard to a necropsy on an eight-year-old child reported by Ingier, which showed a moderate hypertrophy of the left ventricle. We look in vain, likewise, for information on the subject in the work on guinea-pig scurvy by Holst and Froelich, and that on scurvy in the monkey by Hart and Lessing. The first linking of cardiac enlargement with scurvy is found in a paper by Darling, who described “right-sided hypertrophy and degenerative changes in the vagus and all its branches.” Hess described and demonstrated by means of roentgenograms the enlarged heart in infantile scurvy. Recently Erdheim, in an article entitled “Das Barlowherz,” reported the occurrence ofenlargement of the heart, especially of the right ventricle, in 21 out of 31 necropsies of infantile scurvy, and concluded that a direct ratio exists between the degree of enlargement and the intensity of the disorder. These reports gain added interest in view of the enlargement of the right heart so frequently encountered in beriberi, and described by Andrews in infants dying of this condition. In addition to the definite statement of Darling regarding adults, mention may be made of the observation of Aschoff and Koch, that in two cases of uncomplicated scurvy there were fatty degeneration and dilatation of the heart. Fatty degeneration of the muscle is frequent, brown atrophy exceptional. Sato and Nambu also found hyperæmia and atrophy with increase of connective tissue between the muscle fibres.
The pericardial cavity contains almost invariably an increased quantity of fluid, which may be so great as to impede the heart’s action. Adhesive pericarditis has been described. The cardiac valves are normal, unless previously damaged.
Lungs.—The lungs are almost always congested, but apart from this are remarkably free from abnormality. Smaller or larger hemorrhages are described occasionally, which are usually considered truly scorbutic; Andrews, however, found similar lesions in beriberi. In the necropsy of Stephen Mackenzie’s case, described by Barlow, these small hemorrhages are stated to have resembled small red tubercles scattered throughout the lung. There may be pulmonary infarcts. Edema of the lungs is not uncommon, as we should expect, especially as a terminal condition. Pneumonia, lobular or lobar, is one of the most frequent complications and causes of death. Active tuberculosis is a not uncommon secondary manifestation.
Subserous hemorrhages are almost the rule; if infection supervenes, the pleuræ become thickened and covered with an exudate of pus and fibrin.
Alimentary Tract.—The lesions of the gums so well recognized clinically are fully discussed under symptomatology. The remarkable fact that these hemorrhages do not appear in edentulous gums has been the centre of the controversy as to the identity of adult scurvy and Barlow’s disease. This same lack of involvement is noted in adults whose teeth have been extracted. Where teeth are present, the gums are swollen and edematous, often of a livid, reddish color; less frequently, pale and pouting. Hemorrhage is seen at the edge of the gum adjacent to the teeth. In advanced cases the gums are enormously swollen, fungous, ulcerated and covered with a foul, greenish, necrotic mass, which may extend widely over the buccal mucous membrane. The teeth become loosened and fall out. Secondary infection undoubtedly plays the chief rôle in producing this condition, for the most severe forms are found only where caries and pyorrhœa preëxisted. This seat of infection may serve as the source of dissemination throughout the body, giving rise to many of the lesions found at postmortem, especially in the lower part of the intestinal tract.
Thestomachshows no characteristic changes. Congestion of the mucosa is frequent, at times associated with small superficial erosions; the latter gain added interest in view of their occurrence in guinea-pig scurvy. Hemorrhages occur here also and may involve any of the mural coats.
Theduodenumshows often intense congestion. This occurs with sufficient frequency to demand attention, especially as a similar condition has been described in otherdisorders grouped with scurvy. Willcox and others found congestion of the duodenum and of the lower intestine in beriberi, and Andrews described not only congestion but even minute hemorrhages. Small duodenal ulcers are by no means infrequent both in human and in guinea-pig scurvy (Holst and Froelich). The presence of such marked congestion surrounding the papilla of Vater would lead us to expect the occurrence of catarrhal jaundice associated with scurvy. But, on the contrary, icterus has rarely been noted in scurvy. Urizio has described jaundice in this connection, but it is difficult to decide whether his cases were true scurvy, as they occurred in an epidemic of jaundice and no histologic examination of the bones was carried out.
Theintestinemay present a variety of lesions.29The mucosa is frequently congested and swollen, and the solitary follicles and Peyer’s patches enlarged. These changes may progress to necrosis and extensive ulceration. In an outbreak of scurvy occurring in this country in 1917, in a large institution for epileptics, ulceration was a frequent lesion at necropsy.30Dysentery, a frequent complication of scurvy in some epidemics, may add to this ulceration and lead to even complete sloughing of the inner lining of the intestine. Hemorrhages are found in the mucous, serous or muscular layers. Here, as elsewhere, the hemorrhages vary in size from petechiæ to large infiltrations of blood. A very striking picture is sometimes presentedby the pale, edematous intestinal wall dotted or streaked with vivid red.