CHAPTER XII
General Pathology of Traumatic Shock
To demonstrate a relationship between a parenchymal degenerative changeor pattern of changes and the clinical state of shock several conditionsmust be satisfied. The lesions must first be sufficiently distinctive,so that there can be no possibility of confusion with postmortem degenerationor the artefacts of poor fixation and faulty histologic technique. Second,they must be clearly distinguishable from the group of agonal changes seenin the tissues of any person whose death has not been instantaneous orat least relatively rapid. Specificity of individual lesion cannot reasonablybe expected, but the changes should be demonstrable in a high proportionof shock cases, absent in cases of sudden death, and relatively infrequentin cardiac, metabolic, or cerebral deaths in which shock-like states arecomparatively uncommon. There should be a demonstrable time-relationshipbetween the onset of shock and appearance of the lesions, and converselybetween recovery from shock and their disappearance. So far as could beascertained, no pattern of lesions which fulfills these conditions1in 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 thereforeare of interest in relation to its pathogenesis and (2) those which followshock and therefore may be considered as its consequences. In studies ofthe pathology of human shock attention has heretofore been concentratedprimarily on the former. In the present work attention is particularlydevoted to the latter, but two brief sections dealing with pulmonary edemaand with fat embolism have been included because of the extensive considerationgiven to them by previous investigators.
In our own preliminary investigations, the search for possible sequelaeof
1MOON, V. H.: Analysis of shock. Brit. M. J.1: 773-779, June 10, 1944.
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shock seemed fruitless for many months. The postmortem material of severalhundred battle casualties was vainly examined for any lesion or combinationof lesions which would fulfill the imposed conditions. The organs of patientsdying after 4, 8, or 12 hours of prolonged shock showed little evidenceof histologic change and none which could not readily be duplicated ina series of non-shock cases. When, however, the range of investigationwas broadened to include material from casualties who lived more than 18hours after injury, and when frozen sections stained for fat with SudanIV were substituted for paraffin sections, a fairly constant pattern wasdisclosed. Evidence was obtained that approximately 18 hours after a shock-producinginjury, fat vacuolation appears in the parenchymal cells of the heart,liver, and kidneys. These changes increased in frequency and severity upto 96 hours after injury, then progressively declined with longer periodsof 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 withshock. In the adrenal gland a series of changes was readily demonstrable:swelling of the cortex, pseudotubular degeneration, and depletion of stainablelipid, particularly of doubly refractile lipid. Since these changes didnot differ qualitatively and were less marked quantitatively than thoseseen in cases with infection and in other types of control material, theirsignificance is questionable. Only one factor, the depletion of doublyrefractile lipid elements, showed a tendency to reversibility with increasingtime intervals following resuscitation from shock.
Material
The nucleus of material for this section of the study was provided bythe necropsy protocols and corresponding microscopic preparations from60 cases that had been studied clinically by members of the Board. As thework progressed, the importance of sepsis as a complicating factor becameapparent. Additional cases were therefore selected from the files of the15th Medical General Laboratory in which the clinical data were sufficientlydetailed to establish the diagnosis of shock and in which major sepsiscould be excluded. Numerous additional examples of acute shock were includedin order to cover a
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wider time-range than was provided by the Board`s cases. In the tablesto follow, these supplementary cases have been included unless the tablesare designated as "Board Cases."
Control material was drawn both from the 15th Laboratory and from theArmy 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 faras 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 fromaplastic anemia. Not all organs were available for fat stains in all ofthese cases; consequently the number of controls varies somewhat from onesection to another. The starvation and aplastic anemia groups were selectedbecause of the known frequency with which fatty vacuolation of variousorgans occurs under these conditions.
The majority of necropsies on the combat soldier had been performedunder field conditions by an officer of a field or evacuation hospitalwhose experience in pathology was often limited. (In the original 60 cases,one of the Board members was usually present at the necropsy.) Deaths weremost numerous at times of heightened military activity when hospital staffswere overworked in caring for the living. Necropsies were sometimes conductedin hospital operating rooms but more often in tents without benefit offlooring, heat, or adequate illumination. Scales were rarely available.The examinations and records were inevitably incomplete. The central nervoussystem was rarely examined, the intestinal tract seldom opened, and woundsof the extremities were given but cursory attention to determine the presenceor absence of gross infection, major vascular involvement, or extensivenecrosis of muscle. Blocks of representative tissues were fixed in formalin,occasionally in Zenker`s solution, and transmitted to the Pathology Sectionof the 15th Medical General Laboratory where they were sectioned and thehistologic findings were reviewed by the author.
Findings
Lungs
The Board`s cases include no examples of sudden death; hence the lungswere never normal. Congestion was described in every case; edema in approxi-
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mately 85 percent; atelectasis in 70 percent; fat embolism in 65 percent;intra-alveolar hemorrhage in 55 percent; interstitial hemorrhage in 25percent, and pneumonia in 30 percent. Because two of these lesions, pulmonaryedema and fat embolism, have received considerable attention in relationto the mechanism of shock, their significance is worth examining in moredetail.
Pulmonary Edema.-Estimation of the severity of pulmonary edemais difficult from the available data in view of the large number of prosectorsand the few lung weights recorded. A rough classification into three gradeshas been attempted for 47 cases in which adequate information was recordedin the necropsy protocols: Grade I, little or no edema (classified as "slight")with lung weights probably below 800 Gm.; Grade II, moderate edema withlung weights between 800 and 1,200 Gm.; Grade III, severe edema with lungweights 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 inthese patients. It has been suggested2 that pulmonary edemais a constant and integral part of the shock mechanism. It is certainlya common sequela of renal insufficiency, from which a large proportionof the patients in this series suffered. It could be due to myocardialfailure and evidence will be presented later in this chapter that myocardialdegeneration actually was present in many cases. It might be influencedby 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 periodof survival in 47 shock cases. The patients dying in less than 48 hoursrepresent by and large the group in which resuscitation was unsuccessful.One patient (Case 22) briefly appeared to be resuscitated only to developtwo secondary attacks of circulatory failure, in the last of which he died.These patients may fairly be considered to have died in, perhaps of, severeand 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 safeto assume that shock had disappeared. In the majority of these, incipientrenal insufficiency was manifest, and only one patient failed to show anephropathy at
2MOON, V. H.: Shock, its mechanism and pathology.Arch. Path. 24: 642-663 (November) and 794-813 (December), 1937.
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TABLE 101.-SEVERITY OF PULMONARYEDEMA AND SURVIVAL PERIODIN 47 SHOCK CASES
postmortem examination. They were oliguric or anuric, and the plasmanonprotein 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 casesthere was a moderate or severe pulmonary edema, but since in five of themthere was also histologic evidence of myocardial degeneration, it wouldbe impossible to assess the relative importance of cardiac and renal factors.
The 25 patients dying from the fifth day onward have been divided intouremic and non-uremic groups. Pulmonary edema of moderate degree was presentin 6, and of severe degree in 7 of the 17 cases in the former group despitethe fact that many of these patients were treated in consultation withclinical members of the Board and the intake of fluid was rigidly restricted.Since there was histologic evidence of myocardial injury in only 3 patientsof this group, the evidence points strongly to renal insufficiency as theprimary cause of the pulmonary edema. In the non-uremic group, 4 of 8 patientsshowed moderate and only 1 severe edema. In this group the most frequentcause of death was peritonitis.
In summary, pulmonary edema was less frequent and less severe in patientswho were never successfully resuscitated from shock than in those patientswho
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did recover from the acute stage of shock but subsequently displayedevidence of renal insufficiency. Our anatomic data offer no confirmationfor the hypothesis that loss of fluid into the alveoli is an importantfactor in the development of shock.
Pulmonary Fat Embolism.-Pulmonary fat embolism is a very frequentcomplication of battle casualties, as the 65-percent incidence in the presentgroup of cases shows. Its significance is extremely difficult to assess.In the early stages of World War I, much attention was given to it andit was considered by some investigators3 to be an important,perhaps the most important cause of shock. Further experience failed entirelyto substantiate the hypothesis, the theories of Bayliss and Cannon4became dominant, and fat embolism was forgotten.
Frozen sections were cut and stained for fat in all of the present seriesof cases in which lung tissue was available (51 cases). An attempt wasmade 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 arefairly numerous; they are found chiefly in large vessels or arteriolesand seldom have passed into the capillaries of the alveolar walls. In GradeIII a considerable proportion, a quarter to half or more, of the arteriolesare plugged, and in numerous areas capillaries are filled as if by an injectionmass. Systemic fat embolism of significant grade was never found in associationwith Grades I and II but was present in about a fifth of the cases in GradeIII. Judged by experience covering several hundred battle casualties, theauthor considers it improbable that Grades I and II of pulmonary fat embolismare functionally significant.
In Table 102 the grade of fat embolism is compared with the degree ofshock. It is apparent from inspection of the table that Grade III fat embolismwas present in only 8 of the 39 cases of moderately severe or severe shock.Conversely, of 10 patients with significant fat embolism, 8 were estimatedto have moderate or severe shock. It is evident that fat embolism is notthe cause of shock in any considerable proportion of cases. Conversely,severe pulmonary fat embolism was always associated with shock, usuallyof 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`sStationery Office, 1919. IV. CANNON, W. B., and BAYLISS, W. M.: Note onmuscle in relation to shock, p. 19-23. V. BAYLISS, W. M.: Further observationson 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.
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degree. To determine whether or not this relationship is causal wouldrequire the study of a much larger series of cases than the present one.
TABLE 102.-FAT EMBOLISMAND SHOCK IN 51 BOARDCASES
Fat Embolism and Pulmonary Edema.-In Table 103 the grade of pulmonaryfat embolism is compared with the degree of pulmonary edema. It is obviousthat there is no correlation.
TABLE 103.-FAT EMBOLISMAND PULMONARY EDEMA IN44 BOARD CASES
Heart
Material was available from 45 of the Board cases and 61 cases fromthe supplemental series, the latter including 10 shock cases and 51 controlcases. Fat vacuolation was found in 24 of the cases from both series. Thisconsisted
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of very minute vacuoles, seldom more than 2 microns in diameter, arrangedin 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 amountof lipochrome demonstrable at the nuclear poles. The affected cell oftenseemed slightly swollen in the frozen section but this change could notbe recognized with certainty in the paraffin sections. Sometimes singlecells, more often groups of from 10 to 50 adjacent fibers, were affected.Vacuolation was never diffuse throughout the myocardium. In appearanceit was strongly reminiscent of, though usually less severe than the patchyfat vacuolation seen in severe anemia. However, no gross changes suggestiveof "tigering" were ever noted.
The severity of the change, estimated by the number and size of thevacuoles per cell and the proportion of cells involved, was roughly quantitatedon a zero to 3-plus scale. The degree of involvement is compared with thesurvival period in Table 104. It is evident that fat vacuolation of cardiacmuscle cells was not observed in previously healthy young men who developedshock following trauma but failed to survive at least 18 hours. In patientsmanifesting shock who lived from 18 to 96 hours, fat vacuolation of themyocardium was found
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in 75 percent. With longer periods of survival the incidence droppedsharply to 17 percent, and there were no cases of grade 3+ severity.
TABLE 104.-MYOCARDIALFAT VACUOLATION IN 55 SHOCKCASES*
Focal fat vacuolation of cardiac muscle cells has been noted frequentlyby the author in cases of systemic fat embolism with embolization of themyocardial capillaries. In only two of the group under consideration wasthis complication present. These two men died on the fifth and sixth daysafter injury. If they are excluded, the incidence of fat vacuolation inthe patients surviving more than 4 days falls to 11 percent.
In Table 105 the degree of shock and the severity of fat vacuolationare compared in 14 patients among those dying within the 18- to 96-hourperiod who had been examined during life by a clinical member of the Board.The number of cases is small, but increasing intensity of fat vacuolationis apparent as shock becomes more severe.
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Control Cases.-A group of 51 non-shock control cases is shownin Table 106. They include a number of instances of sudden death and amiscellaneous group of medical conditions. Since fat vacuolation can beproduced in experimental animals by short periods of starvation,56 it seemed appropriate to study some cases of starvation deathsfrom prison camps. And, because fatty change in the myocardium has longbeen recognized as a sequela of severe anemia, a series of cases of aplasticanemia was included. Analysis of the material from the point of view ofthe presence or absence of peritonitis, an important factor in relationto liver and adrenal lesions, yielded no evidence that infection was importantin the production of the myocardial changes.
TABLE 106.-FAT VACUOLATIONOF MYOCARDIUM IN 51 CONTROLCASES
Summary.-Fat vacuolation of cardiac muscle fibers is a pathologicprocess not seen in previously healthy persons who die suddenly or whodie 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 injuryfor periods of 18 to 96 hours, but becomes unusual in those living morethan 4 days after injury. In a small sample group the degree of fatty changeappeared to parallel the severity of shock. Though the lesion is foundinconstantly in a variety of medical conditions, particularly those associatedwith severe grades of anoxemia, the frequency is considerably below thatobserved 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 mobilizationin starvation. J. Path. & Bact. 38: 269-284, May 1934.
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Liver
Fat vacuolation of the liver appears in such a variety of conditionsand may be present in so many apparently normal individuals that one isoften tempted to regard it as not significant unless the amount is verygreat. The usual form observed consists of vacuoles of considerable size,ranging from 5 to 20 microns in diameter. Such vacuoles are readily visiblein paraffin sections with low magnification (from 16- to 30-mm. objectives)inasmuch as they occupy the full thickness of the section and appear assharply outlined holes. Because of their large size there are never manyvacuoles in a single cell.
Fat vacuolation of this type was rarely seen in shock cases, and whenfound probably existed before the shock-producing injury. Extensive fatvacuolation was nevertheless readily demonstrable in shock if sufficienttime had elapsed for its development. This form of fat vacuolation consistedalmost entirely of very fine droplets in the range from 2 to 4 micronsin diameter (Fig. 30). Even when the process was severe, though slightlylarger 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 vacuolationis readily seen in paraffin sections if the 4-mm. lens is used. Few ofthem extend through the thickness of the section, but two or more layerscan be seen by varying the depth of focus. Because of the small
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size of the vacuoles, some difficulty may be experienced in frozen sectionsin distinguishing them from the normal pigment which is often slightlysudanophilic. The fat vacuoles are a little larger than the pigment granulesand are rounder. Very often they show a crescentic intensification of thestain on one margin.
The affected cells in the initial stages were always centrally locatedin 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 wholewas not enlarged, yellow, or greasy. For this reason it seems improbablethat 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 periodin 51 Board cases is shown in Table 107. It is evident that in shock patientssurviving from 18 to 96 hours, moderate to severe fat vacuolation was analmost constant finding. With longer survival periods, the proportion ofcases with mild or no fat vacuolation increased but instances of severevacuolation were still found. In reviewing the group of 31 patients whosurvived more than 4 days, it became apparent that severe fatty changeswere particularly frequent in patients with peritonitis, the only commoncause of prolonged sepsis in this series. This is also shown in the table.
Since 26 of the 51 Board cases were complicated by peritonitis, thesignificance of the figures in Table 107 is open to doubt. In Table 108,which includes 28 supplementary cases from the 15th Laboratory, all casesof peritonitis or
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other major sepsis have been excluded. In this selected series, it isapparent that fat vacuolation of more than minimal degree was seldom seenin shock patients who failed to survive at least 18 hours. Of those whosurvived from 18 to 96 hours, 87 percent showed the presence of fat, 59percent in moderate or severe degree. With survival beyond 96 hours, thetendency to return to normal is seen, the total dropping to 47 percentand that for the more severe grades to 29 percent.
Control Cases.-Since fat vacuolation of the liver is such a commonphenomenon and can be produced by so many etiologic factors, numerous controlcases seemed necessary. Seventeen instances of sudden death were selectedat 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 wereincluded-a total of 90 control cases. The incidence of centrolobularfat vacuolation in 36 shock cases and 90 controls is shown in Table109.
The occurrence of moderate or severe fat vacuolation in 24 percent ofthe sudden-death group is worthy of comment. This group was compiled largelyfrom motor-vehicle accident and homicide cases in base-section troops.The proportion of limited-service personnel and older men was higher insuch troops than in combat organizations. Two of the men in the group studiedhad been intoxicated at the time of death and had enlarged, grossly fattylivers suggestive of chronic alcoholism. In contrast, the acute-shock group,with survival periods shorter than 18 hours, was made up almost entirelyof battle
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casualties, all previously healthy and vigorous young men, and thereforerepresents a better control group than the "sudden deaths." Therelatively high incidence (40 percent) in the miscellaneous medical deathsis not surprising in view of the multiple etiology of fat deposit in theliver, 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 surprisingin view of the known frequency of myocardial fat vacuolation in such conditions.The starvation cases provided a most interesting contrast to the shockmaterial. Although fat was present in the majority of these cases, it wasalways manifest at the periphery, never at the center of the lobule.
TABLE 109.-CENTROLOBULARFAT VACUOLATION OF LIVERIN SHOCK CASES AND CONTROLS
Summary.-Eighteen hours after a shock-producing injury, fat vacuolationwas demonstrable in the liver cells at the center of the lobule in 87 percentof 53 cases uncomplicated by major infection and was of moderate or severegrade in 59 percent. After the fourth day it tended to disappear in casesuncomplicated by peritonitis. The incidence in the 18- to 96-hour caseswas somewhat higher than in any of the control group studied.
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Kidney
The histologic changes in the kidney following shock have been describedin detail in Chapter IX. Fat vacuolation in the ascending limb of Henle`sloop (see Figures 9 and 10, Chapter IX) was shown to be the first definitehistologic evidence of renal injury. In the present analysis, only thisfeature of the numerous renal changes which may develop will be considered.The findings in 90 cases are summarized in Table 110. Supplementary shockcases, as previously described, have been added to the Board`s cases.
TABLE 110.-FAT VACUOLATIONOF ASCENDING LIMBS OFHENLE IN 90 SHOCK CASES
As in the heart and liver, fat vacuolation was rarely found in shockpatients surviving less than 18 hours after injury. It was already presentin 55 percent of the 18- to 24-hour group and was evident in 85 percentof those surviving from 1 to 4 days. With survival beyond that period itdecreased somewhat in frequency to 58 percent, and considerably in severity,the 2+ and 3+ grades dropping from 81 percent to 39 percent. In the kidneyas in the heart, the severity of fat vacuolation was uninfluenced by thepresence or absence of peritonitis.
Control Cases.-The degree of fat vacuolation in the ascendinglimbs in 55 control cases is shown in Table 111. Fat vacuolation in theascending limbs of Henle`s loop is found with sufficient frequency (43percent of the "medical" deaths in the present group) to haveled some authors7 to consider it normal.
7MÖLLENDORF, WILHELM VON, ed. Handbuchder mikroskopischen Anatomie des Menschen ... Berlin, J. Springer, 1930.vol. VII, Part I. Harn- und Geschlechtsapparat, p. 86.
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Its complete absence in 19 cases of sudden death and its presence inonly 15 percent of 20 shock cases representing patients who died in lessthan 18 hours following injury clearly indicate that it is not a normalfinding in healthy young men in the 18- to 35-year age group. Dible89 has shown that fat rapidly appears in this segment of the nephronin starvation experiments in rabbits. The data on starvation deaths includedin our series showed an incidence of 50 percent, with 38 percent of 2+or 3+ grade. These figures are nevertheless well below those (85 percentand 81 percent) of the 1- to 4-day shock cases shown in Table 110.
TABLE 111.-FAT VACUOLATIONOF ASCENDING LIMBS OFHENLE IN 55 NON-SHOCKCONTROL CASES
Summary.-Fat vacuolation of the ascending limbs of Henle`s loopis abnormal in men from 18 to 35 years of age. It was found in only 15percent of shock patients dying in less than 18 hours but was present in85 percent of shock patients surviving from 1 to 4 days after injury. Fromthe fourth day onward, a decrease in frequency and severity was demonstrable,regardless of whether a hemoglobinuric nephrosis developed.
Adrenal
A normal adrenal gland is rarely seen at necropsy by the civilian pathologistwho does not have opportunity to perform postmortem examinations upon
8See footnotes 5 and 6.
9DIBLE, J. H., and POPJAK, G.: Distribution of fatty changein kidneys and some factors influencing its production. J. Path. &Bact. 53: 133-146, July 1941.
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persons who have died suddenly without previous disease. The adrenalgland of the healthy young male has a narrow cortex which ranges from 1.0to 1.3 mm. in width. The cells are richly packed with lipid (stainablewith Sudan IV), predominantly in the fascicular layer, but numerous vacuolesare also demonstrable in the zona glomerulosa and reticularis. Limitedto the zona reticularis are large quantities of doubly refractile lipidwhich serve to outline this layer sharply when viewed with crossed Nicolprisms.
In our shock cases no medullary changes but a variety of cortical changeswere observed. The amount of stainable lipid decreased and the opticallyactive fraction was markedly depleted. The cortex was slightly swollenand frequently showed the pseudoacinar type of degeneration described andillustrated by F. B. Mallory in 1914,10 more recently emphasizedby Rich11 in relation to sepsis, and noted by Mallory and Brickley12in the burn victims of the Cocoanut Grove disaster. The changes observeddid not differ qualitatively from and were less severe quantitatively thanthose of sepsis or of such control conditions as aplastic anemia and starvation,though some degree of terminal infection may have complicated much of thiscontrol 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 lipidsare compared in a group of 40 shock cases free from septic complicationsand a control group of 18 cases of sudden death. The amount of lipid, asin other organs, was visually estimated on a zero to 3+ scale. In thisinstance, however, the maximal 3+ figure represents the normal and zerothe stage of maximal depletion.
A moderate depletion of the total stainable fat is evident in the shockgroup surviving from 18 to 96 hours. There is, however, no evidence ofreturn to normal with longer intervals of survival after recovery fromshock; the process is, in fact, much intensified in the group survivingmore than 4 days. In contrast to the stainable lipid, the doubly refractilefraction was occasionally below the usual level in cases of sudden death(17 percent) and was depleted in
10MALLORY, F. B.: Principles of PathologicHistology. Philadelphia, W. B. Saunders, 1914, p. 653.
11RICH, A. R.: Peculiar type of adrenal cortical damage associatedwith 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 managementof Cocoanut Grove burns at the Massachusetts General Hospital; pathology,with special reference to pulmonary lesions. Ann. Surg. 117: 865-884, June1943.
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27 percent of shock patients dying in less than 18 hours, in one caseseverely depleted. In the shock cases of 18 to 96 hours` survival, thistype of lipid was diminished in all but one instance (92 percent of thecases) and markedly so
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in eight cases, or 61 percent. In those patients surviving more than4 days, some evidence of a tendency to return to normal is shown by a dropin the percentage of severe depletion from 61 to 38 percent.
Control Material.-It was difficult to know what kind of controlmaterial would be suitable inasmuch as most types of illness which leadto death produce similar and even more marked adrenal changes. Four groupsof control cases are listed in Table 114. It is evident that a wide varietyof factors affect the storage of lipidic substances in the adrenal cortex,many of them more profoundly than does shock.
TABLE 114.-ADRENALCORTICAL LIPIDS IN 44 CONTROLCASES
Summary.-Although numerous changes occur in the adrenal cortexfollowing shock, they do not differ in character from, and are less severethan 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-producinginjury 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 couldbe established to return toward normal with increasing time intervals followingrecovery from shock.
COMMENT
The possible roles of pulmonary edema and of fat embolism in the pathogenesisof shock in men wounded in battle have been discussed in the sections devotedto these phenomena. The pattern of parenchymal degenerative changes
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described in the heart, liver, kidneys, and adrenals deserves furtherconsideration as a probable consequence of shock. None of the changes describedare specific for the state of shock. Fat is known to make its appearancein one or another of these organs in response to a variety of pathologicconditions such as anoxemia, starvation, and chemical or bacterial toxicagents--and lipids disappear from the adrenal under an even greater varietyof conditions. Critical examination of the data is therefore necessarybefore concluding that the observed changes were due to shock.
Errors of subjective interpretation in relying upon such vague changesas "parenchymatous degeneration" and "cloudy swelling,"which are readily confused with postmortem degeneration and the artefactsof faulty histologic technique, have been avoided by the use of frozensections and fat stains; general histologic experience indicates that thereis no significant shift in the proportion of stainable fat up to 12 hoursafter death. Less is known of the behavior of doubly refractile lipids,but in the material included in this study no evidence was discovered thatthis fraction of the fatty substance was affected by postmortem degenerationwithin the same time limit. The observed variations from the normal aretherefore vital phenomena.
Next in importance are the time relationships to shock. Table 115 showsthe percentage of all cases with abnormal fat vacuolation in the heart,liver, and kidney, and depletion of the doubly refractile lipid in theadrenal, for each group and for the sudden-death control group. In eachof the four organs studied no significant difference in demonstrable fatis apparent between the sudden-death series and the shock cases in whichdeath occurred in less than 18 hours. Abnormal changes are evident, however,in these organs in from 75 to 92 percent of shock patients who survivedfrom 18 to 96 hours after injury. The almost synchronous appearance ofthe lesions 18 hours after injury in all four organs suggests a singlecausative factor. The delay in appearance of the morphologic evidence ofinjury in many instances until shock has been relieved is not incompatiblewith a causal relationship. Days and even weeks may intervene between injuryand reaction with such widely varying agents as diphtheria toxin and x-rays.
Of equal importance in establishing an etiologic relationship betweenshock and the lesions which have been described is evidence of reversibility,of return to or at least toward normal with increasing intervals afterthe episode of shock. As all the necropsy material in this series necessarilyderived from individuals
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with lethal disorders, it is not surprising that a complete return tonormal was not usually demonstrable. Clear evidence of a tendency to reversibilityis shown in Table 116, in which the more severe grades of changes in the18- to 96-hour group are compared with those in the group surviving 4 daysor longer. It is noteworthy that the time interval before recovery wasdemonstrable was essentially the same for all four organs, the change becomingdemonstrable on the fourth day in each instance. The possible contentionthat the changes described were merely agonal, like depletion of liverglycogen, is refuted by this evidence of reversibility in a large numberof cases progressing to a fatal outcome due to other factors.
TABLE 116.-INCIDENCE OF SEVEREFATTY CHANGES IN SHOCKCASES
Though it has been repeatedly stressed that none of the changes describedcan be considered pathognomonic of shock, it is not impossible that thepattern
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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 shockpatients surviving from 18 to 96 hours with three groups of control cases:a miscellaneous group of "medical" deaths, a group of aplasticanemia fatalities, and one of starvation deaths. Only in the shock groupdid more than three-quarters of the cases show involvement of all fourorgans.
Subsequent to making the observations upon the adrenal gland which wehave recorded, our attention was called to the investigations of Popjak13on the lipids in the rat adrenal in experimental shock. He foundswelling of the cortex and marked depletion of both stainable and doublyrefractile lipid. This occurred regularly 15 to 24 hours after the shock-producingcrush injury, a time interval essentially the same as in our human material.In his animals restoration to normal in 48 hours was the rule.
TABLE 117.-DISTRIBUTION OFLESIONS IN CONTROL GROUPSCOMPARED WITH SHOCK CASES
We have little evidence of what the significance of these lesions maybe from the functional point of view. The renal lesion has already beendiscussed in Chapter IX. No electrocardiograms were made on these patientsand no determinations of adrenal cortical hormone excretion were made.In Chapter II the results of bromsulfalein tests in shock patients werediscussed. A transitory period of retention of the dye was observed, whichit seems reasonable to cor-
10POPJAK, G.: Lipids of rat adrenal in shockcaused by experimental crushing injury. J. Path. & Bact. 56: 485-496,October 1944.
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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 bornein mind in interpreting the elevated plasma bilirubin often noted in thesepatients.
SUMMARY AND CONCLUSIONS
Two morphologic phenomena which have been implicated in the pathogenesisof shock, pulmonary edema and pulmonary fat embolism, were studied in aseries of fatal battle casualties. Pulmonary edema was found to be tooinconstant and too late in development to be an important factor in theinitiation of shock in severely wounded men. Pulmonary fat embolism provedto be a frequent coincidental lesion. It was absent or minimal in degreein the majority of cases, and its significance in the small remaining proportioncould not be established.
A standard pattern of visceral changes was found in patients with traumaticshock who survived a minimum of 18 hours after injury. This consisted offat vacuolation of the heart, the central cells of the liver lobules, andthe 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. Fromthe fourth day onward in cases uncomplicated by infection, a tendency toreturn to normal could be demonstrated. The incidence of this pattern ofchanges proved higher in shock cases than in a variety of control material.It was concluded that they constitute evidence of parenchymatous injuryproduced by shock.
