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Chapter XII



General Pathology of Traumatic Shock

To demonstrate a relationship between a parenchymal degenerative change or pattern of changes and the clinical state of shock several conditions must be satisfied. The lesions must first be sufficiently distinctive, so that there can be no possibility of confusion with postmortem degeneration or the artefacts of poor fixation and faulty histologic technique. Second, they must be clearly distinguishable from the group of agonal changes seen in the tissues of any person whose death has not been instantaneous or at least relatively rapid. Specificity of individual lesion cannot reasonably be expected, but the changes should be demonstrable in a high proportion of shock cases, absent in cases of sudden death, and relatively infrequent in cardiac, metabolic, or cerebral deaths in which shock-like states are comparatively uncommon. There should be a demonstrable time-relationship between the onset of shock and appearance of the lesions, and conversely between recovery from shock and their disappearance. So far as could be ascertained, no pattern of lesions which fulfills these conditions1 in man has been described in the literature.

The anatomic changes associated with shock may be usefully divided into (1) those which occur concomitantly with the state of shock and therefore are of interest in relation to its pathogenesis and (2) those which follow shock and therefore may be considered as its consequences. In studies of the pathology of human shock attention has heretofore been concentrated primarily on the former. In the present work attention is particularly devoted to the latter, but two brief sections dealing with pulmonary edema and with fat embolism have been included because of the extensive consideration given to them by previous investigators.

In our own preliminary investigations, the search for possible sequelae of

    1MOON, V. H.: Analysis of shock. Brit. M. J. 1: 773-779, June 10, 1944.


shock seemed fruitless for many months. The postmortem material of several hundred battle casualties was vainly examined for any lesion or combination of lesions which would fulfill the imposed conditions. The organs of patients dying after 4, 8, or 12 hours of prolonged shock showed little evidence of histologic change and none which could not readily be duplicated in a series of non-shock cases. When, however, the range of investigation was broadened to include material from casualties who lived more than 18 hours after injury, and when frozen sections stained for fat with Sudan IV were substituted for paraffin sections, a fairly constant pattern was disclosed. Evidence was obtained that approximately 18 hours after a shock-producing injury, fat vacuolation appears in the parenchymal cells of the heart, liver, and kidneys. These changes increased in frequency and severity up to 96 hours after injury, then progressively declined with longer periods of convalescence from the episode of shock, unless complicating factors, such as fat embolism or severe infection, prevented resolution of the process.

The pancreas and adrenal were also studied in the same group of cases. In the pancreas no lesion was recognized which appeared to correlate with shock. In the adrenal gland a series of changes was readily demonstrable: swelling of the cortex, pseudotubular degeneration, and depletion of stainable lipid, particularly of doubly refractile lipid. Since these changes did not differ qualitatively and were less marked quantitatively than those seen in cases with infection and in other types of control material, their significance is questionable. Only one factor, the depletion of doubly refractile lipid elements, showed a tendency to reversibility with increasing time intervals following resuscitation from shock.


The nucleus of material for this section of the study was provided by the necropsy protocols and corresponding microscopic preparations from 60 cases that had been studied clinically by members of the Board. As the work progressed, the importance of sepsis as a complicating factor became apparent. Additional cases were therefore selected from the files of the 15th Medical General Laboratory in which the clinical data were sufficiently detailed to establish the diagnosis of shock and in which major sepsis could be excluded. Numerous additional examples of acute shock were included in order to cover a


wider time-range than was provided by the Board's cases. In the tables to follow, these supplementary cases have been included unless the tables are designated as "Board Cases."

Control material was drawn both from the 15th Laboratory and from the Army Institute of Pathology. This included several groups of cases: (1) instantaneous or sudden deaths, such as homicides and motor vehicle accidents, (2) "medical deaths" unselected except for elimination, as far as possible, of "shock-like" states (the group included cerebral, cardiac, and infectious diseases), (3) deaths primarily due to starvation (from necropsies done in a German concentration camp), and (4) deaths from aplastic anemia. Not all organs were available for fat stains in all of these cases; consequently the number of controls varies somewhat from one section to another. The starvation and aplastic anemia groups were selected because of the known frequency with which fatty vacuolation of various organs occurs under these conditions.

The majority of necropsies on the combat soldier had been performed under field conditions by an officer of a field or evacuation hospital whose experience in pathology was often limited. (In the original 60 cases, one of the Board members was usually present at the necropsy.) Deaths were most numerous at times of heightened military activity when hospital staffs were overworked in caring for the living. Necropsies were sometimes conducted in hospital operating rooms but more often in tents without benefit of flooring, heat, or adequate illumination. Scales were rarely available. The examinations and records were inevitably incomplete. The central nervous system was rarely examined, the intestinal tract seldom opened, and wounds of the extremities were given but cursory attention to determine the presence or absence of gross infection, major vascular involvement, or extensive necrosis of muscle. Blocks of representative tissues were fixed in formalin, occasionally in Zenker's solution, and transmitted to the Pathology Section of the 15th Medical General Laboratory where they were sectioned and the histologic findings were reviewed by the author.



The Board's cases include no examples of sudden death; hence the lungs were never normal. Congestion was described in every case; edema in approxi-


mately 85 percent; atelectasis in 70 percent; fat embolism in 65 percent; intra-alveolar hemorrhage in 55 percent; interstitial hemorrhage in 25 percent, and pneumonia in 30 percent. Because two of these lesions, pulmonary edema and fat embolism, have received considerable attention in relation to the mechanism of shock, their significance is worth examining in more detail.

Pulmonary Edema.-Estimation of the severity of pulmonary edema is difficult from the available data in view of the large number of prosectors and the few lung weights recorded. A rough classification into three grades has been attempted for 47 cases in which adequate information was recorded in the necropsy protocols: Grade I, little or no edema (classified as "slight") with lung weights probably below 800 Gm.; Grade II, moderate edema with lung weights between 800 and 1,200 Gm.; Grade III, severe edema with lung weights from 1,200 to 1,800 grams. Fifteen cases were Grade I (slight), 14 Grade II (moderate), and 18 Grade III (severe).

Several factors might influence the development of pulmonary edema in these patients. It has been suggested2 that pulmonary edema is a constant and integral part of the shock mechanism. It is certainly a common sequela of renal insufficiency, from which a large proportion of the patients in this series suffered. It could be due to myocardial failure and evidence will be presented later in this chapter that myocardial degeneration actually was present in many cases. It might be influenced by fat embolism and finally it could be brought about, or at least intensified, by over-enthusiastic intravenous fluid therapy.

In Table 101 the degree of pulmonary edema is compared with the period of survival in 47 shock cases. The patients dying in less than 48 hours represent by and large the group in which resuscitation was unsuccessful. One patient (Case 22) briefly appeared to be resuscitated only to develop two secondary attacks of circulatory failure, in the last of which he died. These patients may fairly be considered to have died in, perhaps of, severe and prolonged shock. Five had minimal, 2 moderate, and only 3 severe edema. All had received repeated infusions of plasma and whole blood.

In the patients who survived into the third or fourth days, it is safe to assume that shock had disappeared. In the majority of these, incipient renal insufficiency was manifest, and only one patient failed to show a nephropathy at

    2MOON, V. H.: Shock, its mechanism and pathology. Arch. Path. 24: 642-663 (November) and 794-813 (December), 1937.



postmortem examination. They were oliguric or anuric, and the plasma nonprotein nitrogen had climbed to levels of 90 to 130 mg. per 100 cc., though few or no symptoms of uremia were manifest. In nine of these cases there was a moderate or severe pulmonary edema, but since in five of them there was also histologic evidence of myocardial degeneration, it would be impossible to assess the relative importance of cardiac and renal factors.

The 25 patients dying from the fifth day onward have been divided into uremic and non-uremic groups. Pulmonary edema of moderate degree was present in 6, and of severe degree in 7 of the 17 cases in the former group despite the fact that many of these patients were treated in consultation with clinical members of the Board and the intake of fluid was rigidly restricted. Since there was histologic evidence of myocardial injury in only 3 patients of this group, the evidence points strongly to renal insufficiency as the primary cause of the pulmonary edema. In the non-uremic group, 4 of 8 patients showed moderate and only 1 severe edema. In this group the most frequent cause of death was peritonitis.

In summary, pulmonary edema was less frequent and less severe in patients who were never successfully resuscitated from shock than in those patients who


did recover from the acute stage of shock but subsequently displayed evidence of renal insufficiency. Our anatomic data offer no confirmation for the hypothesis that loss of fluid into the alveoli is an important factor in the development of shock.

Pulmonary Fat Embolism.-Pulmonary fat embolism is a very frequent complication of battle casualties, as the 65-percent incidence in the present group of cases shows. Its significance is extremely difficult to assess. In the early stages of World War I, much attention was given to it and it was considered by some investigators3 to be an important, perhaps the most important cause of shock. Further experience failed entirely to substantiate the hypothesis, the theories of Bayliss and Cannon4 became dominant, and fat embolism was forgotten.

Frozen sections were cut and stained for fat in all of the present series of cases in which lung tissue was available (51 cases). An attempt was made to estimate the severity of the embolism in three grades as follows: In Grade I only an occasional droplet is seen. In Grade II droplets are fairly numerous; they are found chiefly in large vessels or arterioles and seldom have passed into the capillaries of the alveolar walls. In Grade III a considerable proportion, a quarter to half or more, of the arterioles are plugged, and in numerous areas capillaries are filled as if by an injection mass. Systemic fat embolism of significant grade was never found in association with Grades I and II but was present in about a fifth of the cases in Grade III. Judged by experience covering several hundred battle casualties, the author considers it improbable that Grades I and II of pulmonary fat embolism are functionally significant.

In Table 102 the grade of fat embolism is compared with the degree of shock. It is apparent from inspection of the table that Grade III fat embolism was present in only 8 of the 39 cases of moderately severe or severe shock. Conversely, of 10 patients with significant fat embolism, 8 were estimated to have moderate or severe shock. It is evident that fat embolism is not the cause of shock in any considerable proportion of cases. Conversely, severe pulmonary fat embolism was always associated with shock, usually of moderate or severe

    3PORTER, W. T.: Fat embolism, a cause of shock. Boston M. & S. J. 176: 248, February 15, 1917.
    4GREAT BRITAIN. MEDICAL RESEARCH COMMITTEE. Special Report Series, No. 26. Traumatic Toxaemia as a Factor in Shock. Oxford, His Majesty's Stationery Office, 1919. IV. CANNON, W. B., and BAYLISS, W. M.: Note on muscle in relation to shock, p. 19-23. V. BAYLISS, W. M.: Further observations on the results of muscle injury and their treatment, p. 23-26. VI. CANNON, W. B.: Some characteristics of shock induced by tissue injury, p. 27-32.


degree. To determine whether or not this relationship is causal would require the study of a much larger series of cases than the present one.


Fat Embolism and Pulmonary Edema.-In Table 103 the grade of pulmonary fat embolism is compared with the degree of pulmonary edema. It is obvious that there is no correlation.



Material was available from 45 of the Board cases and 61 cases from the supplemental series, the latter including 10 shock cases and 51 control cases. Fat vacuolation was found in 24 of the cases from both series. This consisted


FIGURE 29. Frozen section of myocardium stained with Sudan IV. The patient died 48 hours after a shock-producing wound. Many cells are apparently filled with minute vacuoles, from 2 to 3 microns in diameter, which appear as bright red granules. The affected cells are not swollen and the nuclei appear normal. X 70

of very minute vacuoles, seldom more than 2 microns in diameter, arranged in parallel rows between the myofibrils (Fig. 29). When present in a cell, tht vacuolation was apparent throughout the cell's entire length and breadth, rarely segmentally or focally. It was entirely independent of the amount of lipochrome demonstrable at the nuclear poles. The affected cell often seemed slightly swollen in the frozen section but this change could not be recognized with certainty in the paraffin sections. Sometimes single cells, more often groups of from 10 to 50 adjacent fibers, were affected. Vacuolation was never diffuse throughout the myocardium. In appearance it was strongly reminiscent of, though usually less severe than the patchy fat vacuolation seen in severe anemia. However, no gross changes suggestive of "tigering" were ever noted.

The severity of the change, estimated by the number and size of the vacuoles per cell and the proportion of cells involved, was roughly quantitated on a zero to 3-plus scale. The degree of involvement is compared with the survival period in Table 104. It is evident that fat vacuolation of cardiac muscle cells was not observed in previously healthy young men who developed shock following trauma but failed to survive at least 18 hours. In patients manifesting shock who lived from 18 to 96 hours, fat vacuolation of the myocardium was found


in 75 percent. With longer periods of survival the incidence dropped sharply to 17 percent, and there were no cases of grade 3+ severity.


Focal fat vacuolation of cardiac muscle cells has been noted frequently by the author in cases of systemic fat embolism with embolization of the myocardial capillaries. In only two of the group under consideration was this complication present. These two men died on the fifth and sixth days after injury. If they are excluded, the incidence of fat vacuolation in the patients surviving more than 4 days falls to 11 percent.

In Table 105 the degree of shock and the severity of fat vacuolation are compared in 14 patients among those dying within the 18- to 96-hour period who had been examined during life by a clinical member of the Board. The number of cases is small, but increasing intensity of fat vacuolation is apparent as shock becomes more severe.



Control Cases.-A group of 51 non-shock control cases is shown in Table 106. They include a number of instances of sudden death and a miscellaneous group of medical conditions. Since fat vacuolation can be produced in experimental animals by short periods of starvation,5 6 it seemed appropriate to study some cases of starvation deaths from prison camps. And, because fatty change in the myocardium has long been recognized as a sequela of severe anemia, a series of cases of aplastic anemia was included. Analysis of the material from the point of view of the presence or absence of peritonitis, an important factor in relation to liver and adrenal lesions, yielded no evidence that infection was important in the production of the myocardial changes.


Summary.-Fat vacuolation of cardiac muscle fibers is a pathologic process not seen in previously healthy persons who die suddenly or who die following a shock-producing injury in a period of less than 18 hours. It is found in 75 percent of individuals who have survived a similar injury for periods of 18 to 96 hours, but becomes unusual in those living more than 4 days after injury. In a small sample group the degree of fatty change appeared to parallel the severity of shock. Though the lesion is found inconstantly in a variety of medical conditions, particularly those associated with severe grades of anoxemia, the frequency is considerably below that observed following shock.

    5DIBLE, J. H.: Fat mobilization in starvation. J. Path. & Bact. 35: 451-466, May 1932.
    6DIBLE, J. H., and LIBMAN, J.: Further observations on fat mobilization in starvation. J. Path. & Bact. 38: 269-284, May 1934.


FIGURE 30. Frozen section of liver stained with Sudan IV. The patient died 72 hours after a shock-producing wound. The illustration shows fine fat vacuolation of liver cells.


Fat vacuolation of the liver appears in such a variety of conditions and may be present in so many apparently normal individuals that one is often tempted to regard it as not significant unless the amount is very great. The usual form observed consists of vacuoles of considerable size, ranging from 5 to 20 microns in diameter. Such vacuoles are readily visible in paraffin sections with low magnification (from 16- to 30-mm. objectives) inasmuch as they occupy the full thickness of the section and appear as sharply outlined holes. Because of their large size there are never many vacuoles in a single cell.

Fat vacuolation of this type was rarely seen in shock cases, and when found probably existed before the shock-producing injury. Extensive fat vacuolation was nevertheless readily demonstrable in shock if sufficient time had elapsed for its development. This form of fat vacuolation consisted almost entirely of very fine droplets in the range from 2 to 4 microns in diameter (Fig. 30). Even when the process was severe, though slightly larger droplets were found, there was little tendency for them to fuse, and as many as 15 or 20 might be present in a single cell. The vacuolation is readily seen in paraffin sections if the 4-mm. lens is used. Few of them extend through the thickness of the section, but two or more layers can be seen by varying the depth of focus. Because of the small


size of the vacuoles, some difficulty may be experienced in frozen sections in distinguishing them from the normal pigment which is often slightly sudanophilic. The fat vacuoles are a little larger than the pigment granules and are rounder. Very often they show a crescentic intensification of the stain on one margin.

The affected cells in the initial stages were always centrally located in the lobule; with increasing severity the involvement spread to the periphery. There was little evidence of swelling of the cells and the organ as a whole was not enlarged, yellow, or greasy. For this reason it seems improbable that the amount of fat in the liver could have been greatly increased, though a check by chemical methods would be necessary to decide this point.

The occurrence of small-droplet fat in relation to the survival period in 51 Board cases is shown in Table 107. It is evident that in shock patients surviving from 18 to 96 hours, moderate to severe fat vacuolation was an almost constant finding. With longer survival periods, the proportion of cases with mild or no fat vacuolation increased but instances of severe vacuolation were still found. In reviewing the group of 31 patients who survived more than 4 days, it became apparent that severe fatty changes were particularly frequent in patients with peritonitis, the only common cause of prolonged sepsis in this series. This is also shown in the table.


Since 26 of the 51 Board cases were complicated by peritonitis, the significance of the figures in Table 107 is open to doubt. In Table 108, which includes 28 supplementary cases from the 15th Laboratory, all cases of peritonitis or


other major sepsis have been excluded. In this selected series, it is apparent that fat vacuolation of more than minimal degree was seldom seen in shock patients who failed to survive at least 18 hours. Of those who survived from 18 to 96 hours, 87 percent showed the presence of fat, 59 percent in moderate or severe degree. With survival beyond 96 hours, the tendency to return to normal is seen, the total dropping to 47 percent and that for the more severe grades to 29 percent.


Control Cases.-Since fat vacuolation of the liver is such a common phenomenon and can be produced by so many etiologic factors, numerous control cases seemed necessary. Seventeen instances of sudden death were selected at random from the laboratory files. Fifteen cases of "medical" deaths (cardiac, cerebral, nephritic) without obvious shock-like states, 20 instances of death from aplastic anemia, and 38 starvation deaths were included-a total of 90 control cases. The incidence of centrolobular fat vacuolation in 36 shock cases and 90 controls is shown in Table 109.

The occurrence of moderate or severe fat vacuolation in 24 percent of the sudden-death group is worthy of comment. This group was compiled largely from motor-vehicle accident and homicide cases in base-section troops. The proportion of limited-service personnel and older men was higher in such troops than in combat organizations. Two of the men in the group studied had been intoxicated at the time of death and had enlarged, grossly fatty livers suggestive of chronic alcoholism. In contrast, the acute-shock group, with survival periods shorter than 18 hours, was made up almost entirely of battle


casualties, all previously healthy and vigorous young men, and therefore represents a better control group than the "sudden deaths." The relatively high incidence (40 percent) in the miscellaneous medical deaths is not surprising in view of the multiple etiology of fat deposit in the liver, but is still not as high as the frequency (59 percent) in the 18- to 96-hour shock group. The low incidence in the anemia group proved surprising in view of the known frequency of myocardial fat vacuolation in such conditions. The starvation cases provided a most interesting contrast to the shock material. Although fat was present in the majority of these cases, it was always manifest at the periphery, never at the center of the lobule.


Summary.-Eighteen hours after a shock-producing injury, fat vacuolation was demonstrable in the liver cells at the center of the lobule in 87 percent of 53 cases uncomplicated by major infection and was of moderate or severe grade in 59 percent. After the fourth day it tended to disappear in cases uncomplicated by peritonitis. The incidence in the 18- to 96-hour cases was somewhat higher than in any of the control group studied.



The histologic changes in the kidney following shock have been described in detail in Chapter IX. Fat vacuolation in the ascending limb of Henle's loop (see Figures 9 and 10, Chapter IX) was shown to be the first definite histologic evidence of renal injury. In the present analysis, only this feature of the numerous renal changes which may develop will be considered. The findings in 90 cases are summarized in Table 110. Supplementary shock cases, as previously described, have been added to the Board's cases.


As in the heart and liver, fat vacuolation was rarely found in shock patients surviving less than 18 hours after injury. It was already present in 55 percent of the 18- to 24-hour group and was evident in 85 percent of those surviving from 1 to 4 days. With survival beyond that period it decreased somewhat in frequency to 58 percent, and considerably in severity, the 2+ and 3+ grades dropping from 81 percent to 39 percent. In the kidney as in the heart, the severity of fat vacuolation was uninfluenced by the presence or absence of peritonitis.

Control Cases.-The degree of fat vacuolation in the ascending limbs in 55 control cases is shown in Table 111. Fat vacuolation in the ascending limbs of Henle's loop is found with sufficient frequency (43 percent of the "medical" deaths in the present group) to have led some authors7 to consider it normal.

    7MÖLLENDORF, WILHELM VON, ed. Handbuch der mikroskopischen Anatomie des Menschen ... Berlin, J. Springer, 1930. vol. VII, Part I. Harn- und Geschlechtsapparat, p. 86.


Its complete absence in 19 cases of sudden death and its presence in only 15 percent of 20 shock cases representing patients who died in less than 18 hours following injury clearly indicate that it is not a normal finding in healthy young men in the 18- to 35-year age group. Dible8 9 has shown that fat rapidly appears in this segment of the nephron in starvation experiments in rabbits. The data on starvation deaths included in our series showed an incidence of 50 percent, with 38 percent of 2+ or 3+ grade. These figures are nevertheless well below those (85 percent and 81 percent) of the 1- to 4-day shock cases shown in Table 110.


Summary.-Fat vacuolation of the ascending limbs of Henle's loop is abnormal in men from 18 to 35 years of age. It was found in only 15 percent of shock patients dying in less than 18 hours but was present in 85 percent of shock patients surviving from 1 to 4 days after injury. From the fourth day onward, a decrease in frequency and severity was demonstrable, regardless of whether a hemoglobinuric nephrosis developed.


A normal adrenal gland is rarely seen at necropsy by the civilian pathologist who does not have opportunity to perform postmortem examinations upon

    8See footnotes 5 and 6.
    9DIBLE, J. H., and POPJAK, G.: Distribution of fatty change in kidneys and some factors influencing its production. J. Path. & Bact. 53: 133-146, July 1941.


persons who have died suddenly without previous disease. The adrenal gland of the healthy young male has a narrow cortex which ranges from 1.0 to 1.3 mm. in width. The cells are richly packed with lipid (stainable with Sudan IV), predominantly in the fascicular layer, but numerous vacuoles are also demonstrable in the zona glomerulosa and reticularis. Limited to the zona reticularis are large quantities of doubly refractile lipid which serve to outline this layer sharply when viewed with crossed Nicol prisms.

In our shock cases no medullary changes but a variety of cortical changes were observed. The amount of stainable lipid decreased and the optically active fraction was markedly depleted. The cortex was slightly swollen and frequently showed the pseudoacinar type of degeneration described and illustrated by F. B. Mallory in 1914,10 more recently emphasized by Rich11 in relation to sepsis, and noted by Mallory and Brickley12 in the burn victims of the Cocoanut Grove disaster. The changes observed did not differ qualitatively from and were less severe quantitatively than those of sepsis or of such control conditions as aplastic anemia and starvation, though some degree of terminal infection may have complicated much of this control material. Only one feature, the doubly refractile lipid depletion, showed evidence of reversibility with recovery from shock.

In Tables 112 and 113 the stainable and the doubly refractile lipids are compared in a group of 40 shock cases free from septic complications and a control group of 18 cases of sudden death. The amount of lipid, as in other organs, was visually estimated on a zero to 3+ scale. In this instance, however, the maximal 3+ figure represents the normal and zero the stage of maximal depletion.

A moderate depletion of the total stainable fat is evident in the shock group surviving from 18 to 96 hours. There is, however, no evidence of return to normal with longer intervals of survival after recovery from shock; the process is, in fact, much intensified in the group surviving more than 4 days. In contrast to the stainable lipid, the doubly refractile fraction was occasionally below the usual level in cases of sudden death (17 percent) and was depleted in

    10MALLORY, F. B.: Principles of Pathologic Histology. Philadelphia, W. B. Saunders, 1914, p. 653.
    11RICH, A. R.: Peculiar type of adrenal cortical damage associated with acute infections, and its possible relation to circulatory collapse. Bull. Johns Hopkins Hosp. 74: 1-15, January 1944.
    12MALLORY, T. B., and BRICKLEY, W. J.: Symposium on management of Cocoanut Grove burns at the Massachusetts General Hospital; pathology, with special reference to pulmonary lesions. Ann. Surg. 117: 865-884, June 1943.




27 percent of shock patients dying in less than 18 hours, in one case severely depleted. In the shock cases of 18 to 96 hours' survival, this type of lipid was diminished in all but one instance (92 percent of the cases) and markedly so


in eight cases, or 61 percent. In those patients surviving more than 4 days, some evidence of a tendency to return to normal is shown by a drop in the percentage of severe depletion from 61 to 38 percent.

Control Material.-It was difficult to know what kind of control material would be suitable inasmuch as most types of illness which lead to death produce similar and even more marked adrenal changes. Four groups of control cases are listed in Table 114. It is evident that a wide variety of factors affect the storage of lipidic substances in the adrenal cortex, many of them more profoundly than does shock.


Summary.-Although numerous changes occur in the adrenal cortex following shock, they do not differ in character from, and are less severe than those seen in infection and in a wide variety of lethal disorders. The only factor which was found to change abruptly 18 hours after a shock-producing injury was the amount of doubly refractile lipid in the zona reticularis. This was diminished in 92 percent of the cases in the 18- to 96-hour group (Table 114). This factor also was the only one in which any tendency could be established to return toward normal with increasing time intervals following recovery from shock.


The possible roles of pulmonary edema and of fat embolism in the pathogenesis of shock in men wounded in battle have been discussed in the sections devoted to these phenomena. The pattern of parenchymal degenerative changes


described in the heart, liver, kidneys, and adrenals deserves further consideration as a probable consequence of shock. None of the changes described are specific for the state of shock. Fat is known to make its appearance in one or another of these organs in response to a variety of pathologic conditions such as anoxemia, starvation, and chemical or bacterial toxic agents--and lipids disappear from the adrenal under an even greater variety of conditions. Critical examination of the data is therefore necessary before concluding that the observed changes were due to shock.

Errors of subjective interpretation in relying upon such vague changes as "parenchymatous degeneration" and "cloudy swelling," which are readily confused with postmortem degeneration and the artefacts of faulty histologic technique, have been avoided by the use of frozen sections and fat stains; general histologic experience indicates that there is no significant shift in the proportion of stainable fat up to 12 hours after death. Less is known of the behavior of doubly refractile lipids, but in the material included in this study no evidence was discovered that this fraction of the fatty substance was affected by postmortem degeneration within the same time limit. The observed variations from the normal are therefore vital phenomena.

Next in importance are the time relationships to shock. Table 115 shows the percentage of all cases with abnormal fat vacuolation in the heart, liver, and kidney, and depletion of the doubly refractile lipid in the adrenal, for each group and for the sudden-death control group. In each of the four organs studied no significant difference in demonstrable fat is apparent between the sudden-death series and the shock cases in which death occurred in less than 18 hours. Abnormal changes are evident, however, in these organs in from 75 to 92 percent of shock patients who survived from 18 to 96 hours after injury. The almost synchronous appearance of the lesions 18 hours after injury in all four organs suggests a single causative factor. The delay in appearance of the morphologic evidence of injury in many instances until shock has been relieved is not incompatible with a causal relationship. Days and even weeks may intervene between injury and reaction with such widely varying agents as diphtheria toxin and x-rays.

Of equal importance in establishing an etiologic relationship between shock and the lesions which have been described is evidence of reversibility, of return to or at least toward normal with increasing intervals after the episode of shock. As all the necropsy material in this series necessarily derived from individuals


with lethal disorders, it is not surprising that a complete return to normal was not usually demonstrable. Clear evidence of a tendency to reversibility is shown in Table 116, in which the more severe grades of changes in the 18- to 96-hour group are compared with those in the group surviving 4 days or longer. It is noteworthy that the time interval before recovery was demonstrable was essentially the same for all four organs, the change becoming demonstrable on the fourth day in each instance. The possible contention that the changes described were merely agonal, like depletion of liver glycogen, is refuted by this evidence of reversibility in a large number of cases progressing to a fatal outcome due to other factors.



Though it has been repeatedly stressed that none of the changes described can be considered pathognomonic of shock, it is not impossible that the pattern


of changes may be. This is suggested by the data shown in Table 117. The incidence of the lesions under consideration has been compared in shock patients surviving from 18 to 96 hours with three groups of control cases: a miscellaneous group of "medical" deaths, a group of aplastic anemia fatalities, and one of starvation deaths. Only in the shock group did more than three-quarters of the cases show involvement of all four organs.

Subsequent to making the observations upon the adrenal gland which we have recorded, our attention was called to the investigations of Popjak13 on the lipids in the rat adrenal in experimental shock. He found swelling of the cortex and marked depletion of both stainable and doubly refractile lipid. This occurred regularly 15 to 24 hours after the shock-producing crush injury, a time interval essentially the same as in our human material. In his animals restoration to normal in 48 hours was the rule.


We have little evidence of what the significance of these lesions may be from the functional point of view. The renal lesion has already been discussed in Chapter IX. No electrocardiograms were made on these patients and no determinations of adrenal cortical hormone excretion were made. In Chapter II the results of bromsulfalein tests in shock patients were discussed. A transitory period of retention of the dye was observed, which it seems reasonable to cor-

    10POPJAK, G.: Lipids of rat adrenal in shock caused by experimental crushing injury. J. Path. & Bact. 56: 485-496, October 1944.


relate with the fatty changes in the liver which have been described. Although no morphologic evidence of bile stasis was observed in liver sections, the possibility of a hepatic as well as a hemolytic factor must be borne in mind in interpreting the elevated plasma bilirubin often noted in these patients.


Two morphologic phenomena which have been implicated in the pathogenesis of shock, pulmonary edema and pulmonary fat embolism, were studied in a series of fatal battle casualties. Pulmonary edema was found to be too inconstant and too late in development to be an important factor in the initiation of shock in severely wounded men. Pulmonary fat embolism proved to be a frequent coincidental lesion. It was absent or minimal in degree in the majority of cases, and its significance in the small remaining proportion could not be established.

A standard pattern of visceral changes was found in patients with traumatic shock who survived a minimum of 18 hours after injury. This consisted of fat vacuolation of the heart, the central cells of the liver lobules, and the ascending limbs of Henle's loops in the kidney. In the adrenal gland, the doubly refractile lipid became depleted after the same time interval. In all four organs these changes persisted for 3 days after injury. From the fourth day onward in cases uncomplicated by infection, a tendency to return to normal could be demonstrated. The incidence of this pattern of changes proved higher in shock cases than in a variety of control material. It was concluded that they constitute evidence of parenchymatous injury produced by shock.