PATHOLOGY
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
NECROPSY REPORTS OF SCURVY
======================================================================
Number| | | |
of | Author |Date| Gross | Microscopic
Cases | | | |
------+------------------+----+---------------+-----------------------
ADULTS
Many |Lind |1772|Brief summaries|
51 |von Himmelstein |1843|Brief summaries|
8 |Hayem |1871|Résumé |Brief résumé.
7 |Lasèque & Legroux |1871|Fairly detailed|
7 |Charpentier |1871|Brief summaries|
13 |Sato & Nambu |1908|Fairly detailed|Fairly detailed.
2 |Urizio |1917|Brief summaries|Brief summaries.
1 |Feigenbaum |1917|Brief summary |Brief summary.
23 |Aschoff & Koch |1919|Very complete |Very complete.
INFANTS AND CHILDREN
1 |Smith |1876|Brief report |
3 |Barlow |1883|Fairly detailed|Bones, brief report.
1 |MacKenzie |1883|Brief summary |
1 |Northrup |1892|Brief report |
1 |Cassel |1893|Brief report |
2 |Sutherland |1894|Fairly detailed|Brain and liver, 1 case
1 |Reinert |1895|Very complete |Fairly complete.
1 |Hirschsprung |1896|Summary |
3 |Meyer |1896|Fairly detailed|
1 |Baginsky |1897|Fairly detailed|Brief, bones more in
| | | | detail.
1 |Naegeli |1897|Fairly detailed|Bones only.
1 |Manz |1899|Summary |
5 |Schoedel & Nauwerk|1900|Very complete |Very complete.
1 |Jacobsthal |1900|Very complete |Very complete.
1 |Stoos |1903|Fairly complete|Bones only.
1 |Looser |1905|Summary |
1 |Hoffmann |1905|Summary |Bones only.
1 |Stoeltzner |1906|Bone only |Bone only.
22 |Fraenkel |1908|Résumé |Bones only.
1 |Nobécourt et al |1913|Brief report |Bone only.
3 |Ingier |1913|Brief report |Bones, very complete.
1 |Bahrdt & Edelstein|1913|Complete |Bones, brief report.
31 |Erdheim |1918|Brief summaries|Brief résumé.
1 |Epstein |1918|Very detailed |
----------------------------------------------------------------------
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.
[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
antiscorbutics.
=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.
[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
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.
[33] The beading may have the usual, rounded, smooth, knobby character.
There may be, however, what one might term "angular beading," the
junction taking on a step-like form, as if the abutting 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 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.
[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 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.
[Illustration: FIG. 3.--High power. Section of lumbar cord showing
normal cells in lateral group of right anterior horn.]
[Illustration: FIG. 4.--High power. Section of lumbar cord showing focal
degeneration and absence of cells in lateral group of left anterior
horn.]
=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.
[Illustration: FIG. 5.--Infantile scurvy. Epiphyseal junction of lower
end of femur: (a) calcified cartilage at "Truemmerfeld"; (b) hemorrhage
in the fibrous marrow (Gernest-mark). Bone cortex and trabeculae
abnormally thin. McCallums' Text Book of Pathology. W. B. Saunders Co.]
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.
[Illustration: FIG. 6.--Posterior-anterior view of shoulder of infant
(R. S.) 17 months old. Severe scurvy. Subperiosteal hemorrhage of
humerus, and separation of upper epiphysis.]
[Illustration: FIG. 7.--Anterior-posterior view of same shoulder (see
fig. 6) 22 months later. Complete restitution of epiphysis without
deformity of humerus.]
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.