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.

Willc.o.x 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 a.s.sociated 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 inst.i.tution 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 petechiae to large infiltrations of blood.

A very striking picture is sometimes presented by the pale, edematous intestinal wall dotted or streaked with vivid red.

[29] For details regarding the intestinal lesions in infantile scurvy, the reader is referred to Barlow's description of the case of Stephen Mackenzie, to one necropsy report by Theodor Fischer, one by Hirschsprung, one by Meyer, and five by Schoedel and Nauwerk. The prevailing lesions are hemorrhages, pigmentation, follicular ulceration, and enlargement of the mesenteric glands.

[30] The potato crop largely failed this year, and there was considerable scurvy in the spring, as described in the chapter on antis...o...b..tics.

=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-j.a.panese 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 haematuria 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 a.s.sociated with intestinal ulceration.

[31] Lind writes: "In the months of July and August I opened near seventy large swellings in the groin, proceeding entirely from scurvy."

... "We found the glands under their arm-pits much enlarged and surrounded with purulent matter, as well as the muscles of their arms and thighs." ... "The glands of the mesentery are generally obstructed and swelled. Some of these were found partly corrupted and imposthumated."

=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.

[32] In view of the report of Hart and Lessing of calcium deposits in the adrenal glands of monkeys suffering from scurvy, special attention should be given to this point in necropsies on human beings.

=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 ill.u.s.trated 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 pa.s.sed 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 s...o...b..tic 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.

[33] The beading may have the usual, rounded, smooth, k.n.o.bby character.

There may be, however, what one might term "angular beading," the junction taking on a step-like form, as if the ab.u.t.ting ends of the cartilage and the bone were of unequal size and not well fitted to each other. The cartilage overtops the bone, so that on palpating the joint there is a precipitous fall as we run the finger outward from the surface of the cartilage, or a sudden elevation on palpating the rib from without inward toward the sternum.

This beading of the ribs, which involves mainly the middle tier, was described by Holst and Froelich in their cla.s.sic 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 s...o...b..tic 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.

[34] There seems to be some misconception as to the pathogenesis of the subperiosteal hemorrhage in scurvy. In most reports this lesion is described as if it resulted from a hemorrhage burrowing its way beneath the periosteum and raising it from the subjacent bone. In point of fact, such an event is impossible, as will be fully realized when one experiences the great difficulty in separating periosteum from normal bone. Scurvy involves a periosteum which is not normal; it is insecurely attached to the shaft of the bone, so that it is readily stripped off by hemorrhage.

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 c.o.xa vara. In the author's case, the condition was found in a s...o...b..tic infant who had never stood on its feet. Schoedel suggests that scurvy may at times be the etiologic factor in c.o.xa 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 sh.e.l.l and very brittle. The trabeculae 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 a.n.a.logous 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 const.i.tutes 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 Laseque 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 role in the etiology of these bleedings. Laseque 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 s.p.a.ces. 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 const.i.tute the prevailing cause of death. Tuberculous lesions are also frequently present, and are stated to a.s.sume 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 p.r.o.nounced 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, spirillae, 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 const.i.tute 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 a.s.sociated 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 pseudoleukaemia. 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.