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 nose and 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 some edema about 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 determining the 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 to hemorrhage. 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 exudate may 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 of enlargement 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 pyorrhoea 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.

The stomach shows 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.

The duodenum shows often intense congestion. This occurs with sufficient frequency to demand attention, especially as a similar condition has been described in other disorders 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.

The intestine may present a variety of lesions.29 The 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.30 Dysentery, 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 presented by the pale, edematous intestinal wall dotted or streaked with vivid red.

Liver.—The liver is frequently congested, as would be expected in view of the involvement of the right heart. Erdheim found congestion, however, in only nine among thirty-one necropsies, although enlargement of the heart was present twenty-one times. There may be hemorrhages in the glandular tissue or under the peritoneum. “Cloudy” and fatty degenerations occur occasionally, and in some cases an early cirrhosis. Lind found abscess of the liver, and wrote that in a few instances “the matter or corruption was hardened, as it were, into a stone.”

Spleen.—This organ is usually somewhat enlarged and congested. Charpentier, in the Paris epidemic of 1871, found it often three to four times the normal size and very soft, and Lind tells us that “the spleen was three times bigger than natural, and fell to pieces, as if composed of congealed blood.” It must be remembered that the pathologic as well as the clinical picture of the scurvy of Lind and his time was generally complicated by infection. The enlargement is usually by no means so great, and no doubt is due in part to intercurrent infections. On section, it is found frequently to contain much reddish-brown pigment. Hemorrhage may also occur. In beriberi, Andrews observed frequent congestion of the spleen and also a loss of normal markings.

Pancreas.—There is but one reference to a lesion of the pancreas in scurvy, that of Sato and Nambu, who encountered hemorrhage of this organ in one case among the necropsies performed in the course of the Russo-Japanese War.

Kidneys.—Here again, congestion and hemorrhage are the two lesions most commonly found. The kidneys also may show any of the forms of nephropathy ordinarily recognized, but these must be regarded as complicating conditions and not a part of the true scurvy.

Small hemorrhages may be found in the uterus, bladder or urethra. They are especially common in the bladder, both in man and in the guinea-pig, and in some instances may be the cause of the hÆmaturia noted during life.

Lymph-nodes.—General enlargement of the lymph-nodes has been described, but occurs probably only in advanced cases where a general infection has been superadded. As a rule the enlargement is confined to nodes draining areas where hemorrhage has occurred. On section these nodes are reddish or brownish as the result of the pigment which they contain, the “black and red spots of different sizes” mentioned by Lind. Following infection they may become purulent, resulting in the inguinal buboes so frequently mentioned by the older authors,31 or in the purulent mesenteric nodes associated with intestinal ulceration.

Organs of Internal Secretion.—Until recently these organs have received but little attention. It is probable, however, that in the near future they will be the object of close study and that new information will be acquired as to their condition in this disorder. Hemorrhages are commonly seen in the adrenals, enlarging them greatly and giving them a deep red color; the hemorrhage generally involves mainly the medullary portion.32 It is probable that careful scrutiny will disclose hemorrhages in the other glands of internal secretion. The question of the involvement of these glands will be again considered under the microscopic anatomy, and has been taken up from a functional standpoint in treating of the possible indirect action of the vitamines.

The brain and the spinal cord likewise have been but little studied. It is hardly to be expected that much will be learned from an investigation of the gross pathology of these organs, but the microscopic anatomy offers a promising field of research. Hemorrhage may occur into the brain substance, into the cord or the membranes surrounding them. Pachymeningitis hemorrhagica interna has been described frequently (Meyer, Hayem, Sutherland, Sato and Nambu) and may give rise to the symptoms of meningitis. Sutherland reports an instance where thrombosis of the basal artery was found postmortem. In one case, that of Feigenbaum, hemorrhage of the cord was diagnosed during life and confirmed at necropsy.

The peripheral nerves may be the seat of hemorrhages, the blood lying between the nerve trunk and its sheath. This is particularly well illustrated in the recent work of Aschoff and Koch.

Bones.—Palpation of the body will often reveal distinct lesion of the bones, such as fractures, either ununited or healed with the formation of large calluses; subperiosteal hemorrhages, especially of the distal end of the femur or of the tibia, may be evident to the eye as well as to the touch. Crepitation of the bones may serve to further establish the break in continuity of the bones. This lesion was well known to the older writers. Lind writes that “in some, when moved, we heard a small grating of the bones. Upon operating those bodies the epiphyses were found entirely separated from the bones; which, by rubbing against each other, occasioned this noise.” “All the young persons under 18 had in some degree their epiphyses separated from the body of the bone, this water having penetrated into the very substance of it.” Poupart was also struck by this phenomenon in young adults.

Another bony alteration which is readily palpable is “beading” of the ribs, the counterpart of the rhachitic rosary. This has not been considered a sign of scurvy, and when noted clinically or at postmortem has been passed over without comment, just as has been the case with cardiac hypertrophy. In infants the beading has been attributed to rickets, and this error has been largely responsible for the general opinion that almost all infants suffering from scurvy suffer also from rickets. If we scan the literature with this question in mind, we find numerous casual references to beading of the ribs in scurvy. Fraenkel’s frequently cited case of a child of seven who died of acute scurvy, showed beading of the ribs during life as well as after death. The true scorbutic character of these enlargements was substantiated by microscopic examination. In their pathologic studies on scurvy among soldiers, Aschoff and Koch frequently describe beading of the ribs, which they attribute to an infraction of the costochondral junctions.33 There may be fracture at this junction, or a separation of the cartilages from the sternum, as described by Lind.

This beading of the ribs, which involves mainly the middle tier, was described by Holst and Froelich in their classic report of guinea-pig scurvy, and has been noted by all subsequent investigators in this field. It has usually been called “rhachitic” or “pseudo-rhachitic” in spite of the fact that this junction is the site of typical scorbutic microscopic lesions. Hart and Lessing refer to the “rhachitic rosary” in monkeys, likewise not realizing that it is the product of scurvy.

The subperiosteal hemorrhage has long been recognized as a lesion characteristic of scurvy.34 It occurs exceptionally in the upper extremities, and most commonly at the lower end of the femur; it may, however, involve almost any of the bones, and has been described in connection with the scapula, cranial vault, orbital plate of the frontal bone, ribs, etc. It varies greatly in its size, being confined to a small area or extending a long distance on the shaft of the bone. It rarely is as large as one would expect from external appearance, as much of the swelling is due to edema and hemorrhage into the soft parts. The periosteum rarely becomes separated at the line of junction of the epiphysis and diaphysis. The underlying blood coagulates rapidly, and the periosteum begins to calcify within a few weeks, as shown by the X-ray.

The most frequent site of fracture, or separation of the epiphysis, is the lower end of the femur. This may be accompanied by local swelling, or be discovered at necropsy, or during life by means of the X-ray in cases in which it has not been suspected. An interesting fracture reported by the author, and also mentioned by Kaufmann and by Schoedel, is that of the head of the femur leading to the development of coxa vara. In the author’s case, the condition was found in a scorbutic infant who had never stood on its feet. Schoedel suggests that scurvy may at times be the etiologic factor in coxa vara as well as in some cases diagnosed as congenital dislocation of the hip.

On sectioning the bones longitudinally the cortex is noted to be exceedingly thin, a mere shell and very brittle. The trabeculÆ are so thin and reduced in number that the bone has become a very fragile structure. The marrow is no longer deep red at the ends of the long bones, but yellowish, frequently presenting a patchy appearance. It has a gelatinous consistency. This “Geruestmark” is one of the characteristic anatomical changes of scurvy, and will be fully described in considering the microscopic picture. Hemorrhages can be clearly distinguished in the marrow, and are of varying shades denoting their irregular occurrence. These hemorrhages were considered by Looser to be the cause of the connective-tissue formation in the marrow, but do not occur with sufficient constancy to warrant this interpretation. Moreover, this “frame-work marrow” is found where there is no evidence of previous hemorrhage.

MICROSCOPIC PATHOLOGY

Skin.—As pointed out by Aschoff and Koch, examination of skin which to gross appearance was the seat of typical small hemorrhages, showed various lesions. In some, perhaps the most typical forms, there had been a fresh extravasation of red blood-cells. This condition is found usually in the subepidermal layers, especially in the papillary stratum. These small hemorrhages occur very frequently about the hair follicles and sweat glands, especially when they have been diseased. Where the bleeding has been of long standing, dark brownish pigment deposits are found and all blood-cells may have disappeared. Phagocytic cells are almost always present and may be of the “wandering” or of the more fixed connective-tissue type. Many round cells may be seen in these areas lying between the connective-tissue strands or around the blood-vessels. Rheindorf, as quoted by Tuechler, has called attention to this round-celled reaction, which in many instances gives a picture analogous to the granulomas, and which leads him to infer an infectious origin for these lesions. Other areas which appeared to be the seat of hemorrhage are shown by the microscope to be small abscesses or new connective tissue often loaded with pigment and detritus, apparently representing the final stage of these lesions. Aschoff and Koch have found that suitably-stained preparations frequently show a loss of elastic fibres, which Rheindorf states constitutes one of the earliest changes of this disorder. The blood-vessels in the vicinity of the hemorrhages are congested, especially the capillaries and small venules.

The muscles also present a similar diverse picture of old and recent hemorrhages, pigment deposit and round-celled infiltration. Increase of connective tissue is usually found between the fibre bundles and in some cases where the hemorrhages are apparently of long standing, as evidenced by loss of contour of the red cells and pigmentation of the surrounding areas, this scar tissue formation is very marked. Changes in the muscle fibres themselves have not been encountered by all observers. Hayem describes widespread fatty degeneration and a deposit of pigment within the fibres, Leven a loss of sarcolemma, while LasÈque and Legroux found fatty changes which were equally marked in muscles showing no hemorrhage. On the other hand, Aschoff and Koch, in their careful studies, did not find noteworthy fatty change of the fibres, but observed often that the fibres within the hemorrhagic areas seemed shrunken and were stained abnormally deep with eosin.

In monkeys dying of experimental scurvy, Hart and Lessing describe granules in the muscles, which, judged by their staining affinities, evidently contained calcium and were similar to those found in the adrenal glands.

Blood-vessels.—A similar difference of opinion obtains in regard to the changes in the walls of the blood-vessels, especially of those in hemorrhagic areas. This question is of particular interest because of its bearing on the problem of the mechanism involved in the escape of the blood. Since it has been demonstrated that neither the clotting time nor the viscosity of the blood is markedly changed in scurvy but that weakness of the vessel walls exists, as demonstrated by “the capillary resistance test,” it is natural that we should seek an explanation in the microscopic pathology of the vessels. So far no change has been found. The application of some of the newer stains, such as those for mitochondria and other cell granules, has not been resorted to for this study, and might furnish valuable information.

Hayem found fatty infiltration of the walls of the small veins and capillaries, and believed this to play an important rÔle in the etiology of these bleedings. LasÈque and Legroux also found occasional fatty changes. Other authors have failed to demonstrate similar lesions, or have considered them due to postmortem change. Koch searched in vain for “rents” in the vessel walls to account for the escape of blood. Hyaline degeneration has also been described, but is believed to result from secondary infections and not to be an intrinsic lesion of scurvy (Sato and Nambu, Aschoff and Koch).

Thrombosis of vessels is found both in the neighborhood of hemorrhage and elsewhere, the thrombi at times completely occluding the vessels and giving rise to typical wedge-shaped infarcts. The lung often shows areas of this kind.

Lungs.—Hemorrhages of various size occur in the tissue of the lung or in the air spaces. Hemorrhagic infarcts also have been described, and Sato and Nambu report hyaline degeneration of the blood-vessel walls. Secondary pneumonias, usually broncho-pneumonic in type, are of common occurrence, and in many epidemics constitute the prevailing cause of death. Tuberculous lesions are also frequently present, and are stated to assume fresh activity as the result of the nutritional disorder. Edema occurs frequently, the fluid in the acini often containing red blood-cells. Subpleural hemorrhages, thickening of the pleura, purulent or fibrinous pleurisy are common lesions.

Heart.—Although hypertrophy and dilatation of the heart have been noted by several observers, microscopic changes have rarely been recorded. Meyer, and also Leven, report fatty degeneration of the muscle fibres, which, however, was found by Aschoff and Koch in only one case. Sato and Nambu described an increase of connective tissue, and others anemia and pigmentation. Thickening of the pericardium and subserous hemorrhages also occur.

ALIMENTARY TRACT

Gums.—Where it has been possible to examine the gums of early cases, where swelling, redness or bluish discoloration are the chief symptoms and before secondary infection has set in, the microscopic picture is very similar to that of the skin. Small hemorrhages, round-celled infiltration, increase of connective tissue, clumps of pigment containing cells, or a diffuse deposit of brownish granules complete the picture. Congestion and edema are usually evident. The changes are most pronounced in the deeper layers of the submucosa and about the muscles, leaving the superficial layers strikingly intact, beneath an apparently normal epithelium. In the later stages, erosion of the mucosa occurs, and the upper layers of submucosa become involved. Polynuclear cells appear in great numbers, abscesses and ulcers are formed, which with proper staining can be shown to harbor the various types of mouth bacteria, cocci, spirillÆ, etc. The pigmentation becomes intense, and a marked increase of the newly-formed connective tissue takes place.

The lesions of the stomach are neither characteristic nor, as a rule, very striking. Hemorrhages occur, the larger ones generally in the subperitoneal layers, the smaller ones in any of the coats. Thickening of the wall follows or accompanies these hemorrhages. Superficial erosions of the mucosa or even ulcers may be seen.

The striking congestion of the duodenum has been fully discussed in considering the gross pathology. At any level in the intestinal tract hemorrhage may take place, with the resulting pigmentation and scar tissue formation. The lymphoid structures—solitary follicles and Peyer’s patches—are usually intensely congested and often the seat of hemorrhage. They constitute the sites of predilection for ulcerative processes of the gut. Bacteria can be demonstrated at times in the submucous layers; however, no type has been found to predominate, the flora being composed of the usual intestinal forms. Aschoff and Koch have demonstrated in these ulcers the spirilla and fusiform bacilli so commonly found in the mouth. These follicular ulcers may be found in any part of the intestine, and may be shallow erosions, or extend through the follicle into the deeper tissues. Hemorrhages are commonly located about the follicles. The epithelial layer is edematous, often showing an increased number of cells.

The lymph-nodes may be congested, or edematous and hemorrhagic. Pigment is usually present and in some cases the peripheral sinus is distended with pigment-loaded cells. Where secondary infection has occurred, extensive necrosis of the glands is seen. This is found frequently in mesenteric nodes where severe intestinal lesions are present. The nodes lying in the drainage paths of hemorrhagic areas, especially the inguinal nodes, show active resorption of blood and blood pigments, and, as noted above, may be the seat of infection.

Liver.—In this organ, likewise, no change is found with sufficient regularity to warrant its acceptance as a distinctive lesion of scurvy. Fatty infiltration is, however, very common in the centre as well as in the periphery of the lobules. It is frequently associated with congestion, which may be so great as to lead to atrophy. In one case of Aschoff and Koch the picture resembled that of primary liver atrophy. The organ frequently contains extravasated blood or depositions of old blood pigment. It should be noted that Boerich described early cirrhosis in several of his cases, and that Aschoff and Koch record that one of their severe, acute cases showed “a recent cellular cirrhosis.” An exceptional lesion is reported by Reinert—a “leucocytic” infiltration of the liver and spleen occurring in a three-year-old child, and resembling that seen in pseudoleukÆmia. Finally, it should be remembered in this connection that Hart and Lessing found calcium deposits not only in the muscles and adrenal glands of their monkeys, but also in the liver.

The spleen shares the general congestion of the internal organs. Sato and Nambu invariably found large numbers of pigment granules in this organ. Hirschsprung noted many Malpighian corpuscles, Reinert describes a true hyperplasia of the splenic pulp, and others mention infarcts and subcapsular hemorrhages.

The kidneys are often normal. On the other hand, various forms of nephritis are found, with cloudy swelling or interstitial change—a not infrequent complication of scurvy. More typical of the primary disease are congestion and hemorrhages, the bleedings occurring either under the capsule, into the interstitial tissues, or into the lumina of the tubules. Hayem found fatty infiltration of this organ and Aschoff and Koch a slight change of this kind in one case.

Adrenals.—A new interest in the study of the adrenals in diseases of the “deficiency” group has been created by the recent work of McCarrison. This author found the adrenals increased in size and weight in guinea-pigs dying of scurvy, whereas the adrenalin content of these glands was markedly decreased. On section there was hemorrhagic infiltration, “usually circumscribed in extent and situated around the periphery of the adrenal cortex.” This was seen even in early cases before hemorrhage had occurred elsewhere in the body. He describes also “degenerative changes in the cellular elements of cortex and medulla” consisting of vacuolation and disintegration of the cells with disappearance or loss of staining reactions of their nuclei. Rondoni, some years previously, had called attention to this increase in size and hyperÆmia of the adrenals in guinea-pigs fed exclusively cereal diets. He, as well as McCarrison, noted an increase, though much less marked, as the result of starvation. LaMer and Campbell recently have confirmed McCarrison’s report of an augmentation in the weight of the adrenal glands in guinea-pigs fed on diets deficient in the antiscorbutic factor.

Comparable lesions have as yet not been found in human scurvy. These glands have been found normal by Jacobsthal, Schoedel and Nauwerk, Ingier and Epstein. In the cases of Aschoff and Koch no abnormality was noted except an almost constant increase in lipoid content. In those of Boerich the glands were normal in all but one case; in this instance the medulla was somewhat increased in size. In passing, we may repeat that Hart and Lessing found calcium deposits in the adrenals of four of their five monkeys, a lesion which has never been recorded in man.

It is valuable in this connection to compare the adrenal in scurvy with that of beriberi. In this disorder, Albert found the adrenal normal in one case, and Andrews describes only congestion in his eighteen necropsies. Ono found an increased adrenalin content in nine fatal cases, and states that the medulla appeared “fatter” than normal. More data will have to be obtained before it can be determined whether characteristic changes occur in scurvy, and how to interpret the hypertrophy described by several authors as common to guinea-pig scurvy.

Pancreas.—Sato and Nambu appear to be the only investigators who have described lesions in the pancreas. They found hemorrhages in one case among thirteen.

Thymus.—This organ has rarely been examined. Aschoff and Koch found no abnormalities in adults, nor did Jacobsthal in a case of infantile scurvy. Boerich noted enlargement in one instance.

Other Organs of Internal Secretion.—Very little attention has been paid to these organs. Aschoff and Koch state that the thyroids and hypophyses were normal in their cases.

Generative Organs.—No abnormalities have been described.

Central Nervous System.—The most frequent abnormality of the central nervous system is, as would be expected, hemorrhage; this has been discussed in the section dealing with gross pathology. No specific changes have been found in nerve-cells or fibres of the brain.

In a case of fatal scurvy in an infant a “focal degeneration of the lumbar cord” has been described, extending for a distance of about a quarter of an inch (Hess). The lesion differed from that of poliomyelitis in the absence of round-celled infiltration and of the characteristic changes in the anterior horn cells (Figs. 3 and 4). The outstanding feature was a loss of cells in the lateral groups of the left anterior horn; there were also fewer nerve fibres in this region, but this diminution was less striking. No definite interpretation of this case can be made as the data are insufficient to permit a conclusion as to whether the lesion was truly scorbutic or the result of an associated process. Schoedel and Nauwerk found no change in the spinal cord stained by Marchi’s method.

Peripheral Nerves.—The sheaths of the large nerves as well as those of the vessels are very often invaded by hemorrhage. The extravasated blood is found to lie around but rarely among the nerve fibres, which do not show any pathological alteration. Ingier is one of the very few to describe a degeneration of the nerve fibres. In one guinea-pig in which scurvy was induced she found “many marked degenerated fibrillar bundles of both sciatic and peroneal nerves, slight degeneration of the phrenic nerves and one vagus and its cardiac branch.” Another animal is referred to as having shown “very marked and well-developed degeneration of the nerves of the lower extremities.” It is open to question whether starvation played a rÔle in the causation of these lesions. Schoedel and Nauwerk, and Aschoff and Koch examined these nerves but failed to find any lesions; the latter directed their attention especially to the vagus of twenty-two cases.

Retinal hemorrhages were found by Jacobsthal, and by Kitamura, who records “decided edema of the retina, marked bleeding and circumscribed hypertrophy of the nerve fibres” such as is found in albuminuric retinitis. These changes are considered again under the symptomatology of scurvy.

Bones.—Our knowledge of the minute pathology of the bones is far more complete and detailed than that of any other structure. This was to be expected in view of the fact that this is the only tissue in which the lesions are diagnostic. In considering the microscopic pathology it must be remembered that all the bones are rarely affected by scurvy, and that those that are involved show the scorbutic changes to a varying degree. One of the peculiarities of the lesion is that it involves the end of the diaphysis or rather the junction of the diaphysis and the cartilage. The bones most apt to show typical changes are the ribs; we shall therefore describe a section made through a costochondral junction.

The costochondral junction is generally swollen, somewhat beaded, and when cut longitudinally shows on gross examination a transverse yellowish bar, corresponding to the area of disorganization which will be described below. Under the microscope the line of juncture is not sharp and straight as is normally the case, but presents a wavy or irregular contour, the cartilage jutting into the bony end of the rib, instead of abutting in neat apposition to it. The bone is hollowed out and irregularly concave, whereas the cartilage presents a convex appearance. At the site of the junction is the Truemmerfeld area, where the normal tissue is splintered and fragmented. Everything in a state of disorder—trabeculÆ of bone of various shapes and sizes lie scattered about, the cells irregularly arranged and much distorted, signs of recent hemorrhage, unrecognizable detritus. The picture is that of weakened bone having been crushed by the pressure of the more compact cartilage. Higher magnification shows that there are few osteoblasts (generally associated with the deeper fragments of bone), a varying number of intact red cells, according to the occurrence of hemorrhage, and occasional spindle- and star-shaped connective-tissue cells. Covering this mass of detritus there is frequently, as Aschoff and Koch have emphasized, more or less protective fibrin which has undergone some hyaline or connective-tissue organization.

The cartilage is also not normal. Its cells do not present an orderly arrangement, the proliferating columns having disappeared in the central convex portion, and being present to a varying extent near the periosteal borders. If we judge from sections of early scurvy in guinea-pigs, this disturbance of the columnar formation of the proliferating cartilage is one of the early signs of scurvy, and is associated with an unevenness and irregularity in shape and size of the bone trabeculÆ. In young individuals, where cartilage activity is great, these changes are most marked and the entire zone of active cells may be somewhat widened.

Below the Truemmerfeld is the Geruestmark or framework marrow, another distinguishing feature of scurvy. This extends for about 5 to 10 mm. toward the lymphoid marrow, where it ends more or less abruptly. It is composed of a loosely-constructed fibrillar tissue on a gelatinous-appearing groundwork, of sparsely scattered cells, and bony trabeculÆ which are markedly thin and weak. Here and there are hemorrhages and blood pigment, especially adjacent to the “Truemmerfeld.” Another feature which strikes one at first glance is that the entire marrow area is incompletely filled by the thin and greatly-depleted trabeculÆ of the spongiosa. The question has been raised whether this rarification is to be considered entirely of scorbutic origin. It is due evidently to a lack of function of the osteoblasts, which are diminished in number, and are represented by a layer of shrivelled spindle cells along the walls of the atrophied bony columns. They may fail almost entirely, as may its osteoid border, which is significant of active bone tissue. The lack of bony structure and rarification clearly is not due to an increase in the number or the function of the osteoclasts, for these do not appear in excess. It is mainly the result of normal bone resorption with a lack of normal bone regeneration. Aschoff and Koch suggest that the framework marrow may be able to manufacture bone, but cannot accomplish this because there is a lack of material from which to make osteoid tissue. This, they believe, constitutes the primary deficiency—a lack or faulty development of cement substance, which in turn may depend on an alteration of colloid material. Regarded in this light, the lesions of the bones resulting in fracture and those of the blood-vessels resulting in rupture and hemorrhage are dependent on a deficiency of the same basic material.

Hemorrhage occurs in the bone as elsewhere; it is almost never lacking. It appears either as large hemorrhages in the spongiosa, especially where the normal marrow joins either the Geruestmark or the Truemmerfeld, or merely as scattered cells, possibly the result of diapedesis. The blood-vessels in these areas are narrow and extremely thin-walled. The most typical site of hemorrhage is beneath the periosteum, a lesion widely known on account of its clinical significance (Fig. 16). Here the blood may extend for a considerable distance along the shaft, but rarely beyond the epiphyseal line. The clot forms readily, demonstrating that the nature of the hemorrhage is not a defect in coagulation, and in its midst may be seen fibrin, pigment, granulation tissue, and more or less firm connective tissue—constituting the callus. The inner surface of the periosteum is frequently lined with newly-formed bone and with a more or less dense deposition of lime salts, which becomes heavier in the course of the healing process, and is readily observed in radiographs. This periostitis ossificans may result in the clot being surrounded by a perfect shell of bone, with bony columns penetrating the deeper layers.

As the result of the lack of bone formation and the consequent weakening of the corticalis and the spongiosa, frequently a separation of the diaphysis from the epiphysis results. This lesion should not be regarded as a true separation, for, as Barlow pointed out, the line of cleavage is not at the junction, but below it, involving the uppermost region of the diaphysis. It is therefore correct to speak of a fracture or infraction. This lesion is generally accompanied by a deformity of the surface contour of the junction, due to a displacement of the cartilage, as a result of which “angular beading” of the rib is brought about. In some instances the cartilage is “telescoped” into the crushed end of the bone. To a varying extent fibrin covers the end of the fractured bone; the angles adjacent to the periosteum contain blood which becomes organized into dense connective tissue, thus serving as a splint for the fractured parts. In the course of healing a large number of foreign body giant-cells appear, blood-vessels sprout from the periosteum as well as the bony surface, and the necrosed tissue gives place to an active formation of callus, which generally leads to complete regeneration and restitution. It is remarkable how quickly and perfectly an epiphysis may become reunited to its shaft (Figs. 6 and 7). Sometimes, however, this takes place with resulting deformity, as in the development of coxa vara of the femur.

As Czerny and Keller have stated, it is difficult to define sharply the relation of bone fragility to scurvy. Histologically there is great similarity between the “osteotabes infantum” described by Ziegler and conditions sometimes found in infantile scurvy. The main distinction is that in the latter disorder the lesion is less generally distributed throughout the skeleton, and is particularly marked in a limited area of the bones (epiphyses). In considering this question it should be borne in mind that, experimentally, osteoporosis and scurvy can be brought about by diets which are absolutely dissimilar. For example, Bartenstein showed that young guinea-pigs develop osteoporosis and multiple fractures on a diet of raw milk containing an adequate quota of antiscorbutic vitamine.

Rickets and infantile scurvy are commonly found associated, although they bear no causal relationship to each other. The distinctive characteristic of rickets is the broad area of osteoid tissue which is formed at the epiphyseal junction, a broad band of incompletely calcified cartilage not found in scurvy. In the latter disease osteoblastic bone growth is greatly inhibited, but what growth does take place occurs in a normal and orderly manner. The osteophytes, for example, which so commonly develop at right angles to the axis of the bone in the subperiosteal hemorrhages, are composed of apparently normal bone. Another marked distinction between the two conditions is the paucity of blood-vessels in the cartilaginous area and in the marrow in scurvy, compared with the increased vascularity so generally encountered in rickets. It is evident, therefore, that although these two nutritional disorders bear a superficial resemblance to each other pathologically, they are radically different and almost antithetical.