CHAPTER IV
Diagnosis of Lower Nephron Nephrosis Resulting from Traumaand Shock ("Shock Kidney")
As Derived from Clinicopathologic Correlation
The clinical syndrome of renal insufficiency following traumatic shockhad not yet, to our knowledge at the time of this study, been defined inthe medical literature. In the interval preceding publication Lucké1has described, from both clinical and pathologic points of view, a groupof similar cases under the term "lower nephron nephrosis." The presentstudy, though now no longer novel, was done independently before his publicationand therefore offers unbiased confirmation which seems worthy of record.Since civilian practice brings so few apposite cases under the observationof any single group of investigators, one of our clearest obligations wasto attempt definition of this syndrome.
In exploration of a new syndrome the first necessity is establishmentof a base of departure; that is, an apparently new combination of symptoms,signs, laboratory observations, or distinctive morphologic lesions. Withwidening experience, additions to and subtractions from this combinationare made until the pattern becomes stabilized, the diagnostic importanceof each feature or group of features being assessed by the frequency withwhich it occurs in the disease in question as compared with its infrequencyin other conditions.
Since the case fatality rate of this condition was high, there is littlerisk of distorting the picture by using the fatal cases to establish thebase of departure. In 38 of 60 cases in which necropsy material was available,pigment nephropathy,
1LUCKÉ, B.: Lower nephron nephrosis. Mil. Surg. 99: 371-396, November 1946.
111
the characteristic renal lesion of "shock kidney" which will be describedin Chapter IX, was present. In the following discussion the symptomatologyin these cases will be presented, comparing the findings as we proceedwith the control group of 22 cases in which pigment nephropathy was provedabsent at necropsy. To determine whether diagnosis of renal injury canbe established beyond reasonable doubt, the fatal cases will be furthercompared with nonfatal cases in which there was evidence of kidney dysfunction.
Objective Evidence of Renal Insufficiency in Casesof Histologically Proved Nephropathy
Oliguria and Anuria
For purposes of this study, oliguria was defined as a 24-hour outputof urine greater than 100 cc. and less than 600 cc.; anuria as an outputnot exceeding 100 cc. per day. Urine output, known in 35 of the above-mentioned38 patients with the characteristic renal lesion, had been subnormal forone or more days in all, 15 patients remaining in the oliguric and 20 reachingthe anuric level. Oliguria or anuria was present from the onset of shockin all but one case, and in this case the delay was apparent rather thanreal. The initial shock had been mild, but secondary shock of greater severityoccurred after operation and was promptly followed by anuria. The majorityof patients showed progression from oliguric to anuric levels, but occasionallyanuria was present from the start. In 15 patients with clinical uremiaand histologically proved nephropathy, the urine output never declinedbelow the oliguric level. It is worth emphasis that these individuals,often casually referred to as "anuria cases," may never in fact becomeanuric. Unless 24-hour outputs are carefully measured, significant oliguriamay easily be missed.
Nine patients with oliguria (or anuria) failed to show a significantrenal lesion at necropsy. This is not surprising, considering the varietyof conditions from which these severely wounded men suffered which wouldtend to lower urine output, such as deficient blood volume, prolonged hypotension,paralytic ileus, infection, and exudation into traumatized areas and intoinfected serous cavities. In two of the nine oliguria or anuria was intermittent;in both the clinical picture was dominated by severe peritonitis.
112
Azotemia
"High azotemia," arbitrarily defined as a nonprotein nitrogen levelin the plasma of 65 mg. per 100 cc. or higher, was found in 36 of the 38proved nephrotic cases; in 1 case no determination was available, and inthe remaining 1, death occurred within 35 hours of injury. In this patientthe nonprotein level had already climbed to 63 mg. per 100 cc., only 2points below our arbitrary limit, and there can be no reasonable doubtthat this limit would have been passed had he lived a few hours longer.Like oliguria, nitrogen retention was evident from the outset. The retentionlevel climbed steadily, usually from 30 to 40 points a day, the maximallevel depending solely on the length of time elapsing before death ensuedor, in those who survived, before onset of diuresis. Nitrogen retention,like oliguria, was also observed in the absence of a renal lesion (7 instances)and is explainable on similar grounds.
Hypertension
We defined hypertension for purposes of this study as an elevation ofthe systolic blood pressure to or above 135 mm. Hg and of the diastolicto 90 mm. Hg or higher. By civilian standards these figures must seem low,but it is to be remembered that we were dealing primarily with a homogeneousgroup of young men between 18 and 30 years of age who had recently sufferedsevere trauma usually associated with the loss of considerable amountsof blood. By this standard, 20 of 32 patients with the renal lesion whoseblood pressures had been recorded were judged to have significant elevationsof systolic or diastolic pressure or both. Hypertension rarely appearedwithin the first 48 hours; it was frequent by 72 hours, and was the ruleby 96 hours.
Of the remaining 12 patients with the characteristic renal lesion whofailed to show an elevation of blood pressure, 3 died within 2 days ofinjury and 6 on the third day. In only 3 patients living beyond the 3-dayperiod did hypertension fail to develop. One died on the fourth, 1 on thefifth, and 1 on the seventh day respectively. The last 2 patients alsohad a severe progressive peritonitis. It seems reasonable to conclude thathypertension is a characteristic if not constant symptom of the syndrome.
The importance of hypertension is increased when viewed from the conversepoint of view. No patient in this series whose kidneys failed to show pigment
113
nephropathy at necropsy had a sustained elevation of blood pressure,although an occasional determination might have been above the arbitrarylimit. It must be remembered, however, that no cases of cerebral injurywere included in our series. In such cases hypertension secondary to increasedintracranial pressure is of course frequent.
Pigment Excretion in the Urine
As part of the routine urine examination of all patients included inthis study, the supernatant urine after centrifugation was tested withbenzidine for the presence of dissolved heme-containing pigments,2which, as will be discussed fully in Chapter VIII, were largely hemoglobinand myoglobin.
All patients with morphologic evidence of renal damage excreted benzidine-positivematerial in the urine. In 11 patients (exclusive of those in whom therewas direct trauma to the urinary tract) enough pigment was excreted tomake the urine grossly red or brown. In some cases descriptions such as"dark amber" suggest a pigment element, but in the majority amber and yellowwere the colors recorded, and only the benzidine test revealed the pigmentelement. Pigment excretion, furthermore, was in most instances transitoryand usually disappeared on the third or fourth day. On the other hand,pigment excretion was observed in 6 patients whose kidneys did not showsignificant lesions at necropsy.
Other Urinary Findings
Other chapters of this volume contain complete discussions of the chemicalabnormalities found in the blood and urine and the results of renal functiontests performed during the course of the studies. Repetition would be pointless,especially since these factors have little diagnostic value. However, threeurinary abnormalities, determination of which lies within the realm ofroutine clinical pathology, are worthy of mention since, although of limiteddiagnostic value, they were constant features of the syndrome.
1. Proteinuria.-All patients with proved renal lesions showedproteinuria. However, since proteinuria was absent in only 14 of the entireseries of casualties studied and was present in 51 patients without clinicalor anatomic evidence of nephropathy, its diagnostic import is negligible.
2See Appendix C, section on routine, urinalyses, for technique of performing the test.
114
2. Persistent Acidity.-The urine of all patients manifestingnephropathy at necropsy was acid on initial examination. The range of pHwas from 5.0 to 6.9 with an average value of 5.8. The urines of the controlgroup ranged from 5.0 to 8.4 with an average of 6.2, overlapping too muchto give the figures any diagnostic value. In succeeding specimens the urinefrom the nephropathic group remained persistently acid with few exceptions,occasionally even despite a therapeutically-induced alkalosis.
3. Fixation of Specific Gravity.-The specific gravities of theinitial specimens varied from 1.009 to 1.032, though the majority of specimensfell within the range of 1.020 to 1.026. No significant difference wasfound in patients with and without nephropathy. Diversity in these initialspecimens is not surprising, since it is probable that in many instancespart of the urine may have been excreted by the kidney before the patientwas wounded. With the passage of time the specific gravity of subsequentspecimens declined in the nephropathic group, despite oliguria, and a tendencyto fixation between 1.010 and 1.015 became apparent in all the patientswith proved renal lesions. Evidence of continued power of urine concentrationoccasionally helped to distinguish cases of "extrarenal" oliguria and azotemiafrom the true nephropathies.
Summary: Diagnosis of Lower Nephron Nephrosis ("ShockKidney")
Seven phenomena have been described which are characteristic of therenal lesion following traumatic shock. One of these, proteinuria, hasno diagnostic value because of its frequency in non-nephropathic cases.Two others, persistent acidity of the urine and fixation of specific gravityat a low level despite oliguria, are of great interest in defining thephysiologic abnormality, but proved of limited diagnostic value since therapeuticemergencies frequently prevented verification by suitable test. A tetradof findings--oliguria, azotemia, pigment excretion, and hypertension--wereof practical diagnostic value.
Each of these may be present singly in patients with normal kidneys.So may any pair. The combination of oliguria and azotemia, for instance,was found five times; even the triad of oliguria, azotemia, and pigmentexcretion was found twice in patients with morphologically normal kidneys.The complete tetrad, however, was never found in this series in patientswith normal kidneys. Barring the complication of a head injury, it wasconcluded that this tetrad might be considered reliable evidence of renaldamage.
115
Uremic Symptomatology
Subjective symptoms of the type commonly to be expected in uremia wereconspicuous primarily by their absence. In the initial stages of the disorderminor symptoms might well have been masked by the greater discomforts ofrecent trauma, surgery, and anesthesia, or been suppressed by postoperativenarcosis. As the days pass, these distractions cease to be of importance,yet again and again statements such as "patient comfortable" and "no complaints"appeared in the records. A brief review of the usual symptoms of renalinsufficiency, noting their frequency in this material, is in order.
Headache.-Headache was not mentioned in any case record. Minorcomplaints might not have been recorded, but even so headache could nothave been a conspicuous feature.
Nausea and Vomiting.-Many of our patients had abdominal woundswith subsequent gastric and intestinal surgery complicated by various gradesof peritoneal irritation. They were often treated by Wangensteen drainage,making interpretation of gastro-intestinal symptoms difficult. Nausea appearedin three of the crush-syndrome cases and also in three others not complicatedby abdominal wounds. In only two of these was it associated with vomiting,once on the seventh and once on the thirteenth day. Persistent hicuppingwas twice recorded.
Vision-No patient complained of visual difficulties. Eyegroundexaminations were recorded in nine cases. In six patients the eyes werefound to be normal when examined at intervals of from 3 to 10 days, andin three patients were found to be abnormal. Two of the latter patientsshowed retinal hemorrhages on the fifth and tenth days of disease, respectively,and one showed papilledema on the ninth day.
Consciousness.-Drowsiness was the most frequent cerebral symptomand was noted in 17 instances. Its onset was recorded as early as the secondday, as late as the ninth. Very frequently the notation was accompaniedby a statement such as "patient drowsy but when aroused answers questionsclearly and intelligently." One patient was frankly disoriented, and twowere irrational. In 11 patients drowsiness progressed to stupor; in 6 ofthese the condition was described as coma. This stage seldom antedateddeath by many hours. Onset of coma was recorded as early as the third andas late as the tenth day. At the time of onset, the nonprotein nitrogenlevels ranged from 89 to 305 mg. per 100 cc. of plasma. One patient regainedconsciousness after a lapse of 2 hours at a time when the
116
nonprotein nitrogen level was 339 mg. per 100 cc. of plasma.
Twitchings and Convulsions.-These were very uncommon phenomena.Twitchings were recorded in two patients, convulsions in four; one of thesefour recovered. Neuromuscular irritability was noted in two other patientsin whom Chvostek`s sign developed. In both, the symptoms followed vigorousalkali therapy.
Hyperpnea.-Dyspnea or hyperpnea was recorded on 12 occasions,with onset ranging from the fourth to the twelfth day. In six instancesit appeared approximately coincidentally with the onset of pulmonary edemaand may well have been an effect of the latter. In only a few instanceswas respiration clearly of the Kussmaul type.
Edema.-Evidence of edema was observed in 25 patients. It appearedas early as the third and as late as the eleventh day, largely dependingon the extent of intravenous fluid therapy. Clinical evidence of pulmonaryedema was recorded in 12 instances. Either pulmonary or peripheral edemamight appear first, and each was observed in the absence of the other.Facial edema was noted only 8 times.
Nonfatal Cases
In examining the clinical records of nonfatal cases in this series tosee if diagnosis of renal injury could be established beyond reasonabledoubt, we were hampered by incompleteness of observation and record. Thefindings in 44 patients whose records were fairly complete and who manifested1 or more of the 4 criteria described above are summarized in the accompanyingtable.
Three patients presented the complete tetrad of characteristic findings.Two showed the triad of pigment excretion, azotemia, and hypertension,but in both there was uncertainty regarding urine output during the first48 hours after injury. Two presented the combination of pigment excretion,oliguria, and azotemia, but blood pressure determinations at appropriatetime intervals were not recorded. In five others with the same triad, hypertensioncould be definitely excluded.
Among those with a combination of two principal signs, one patient showedoliguria and hypertension, but nonprotein nitrogen was not determined andthe urine was not tested with benzidine. In one case hypertension of notablelevel (170/120) and azotemia were observed, but urine output was not recorded
117
TABLE 51.-PRINCIPAL FINDINGSIN 44 SURVIVING PATIENTSSUSPECTED OF HAVING RENALINSUFFICIENCY
nor was the urine tested with benzidine during the first 5 days. InCase 130, oliguria and unimpressive azotemia of 69 mg. per 100 cc. weredemonstrated, but again the urine was not tested and no postoperative bloodpressures were recorded. In another patient, azotemia and pigment excretionwere present but no elevation of blood pressure occurred, and the urineexcretion for the first 24 hours was 750 cc., which was above our arbitrarylimit but nevertheless in the lower range of normality.
Three patients presented the remaining pair of findings: pigment excretionand oliguria. Six patients manifested only transitory oliguria withoutsupporting evidence of nephropathy, and 19 pigment excretion with similarlack of confirmatory findings. In the light of the above findings, letus again evaluate our diagnostic criteria.
As in the fatal group, no patient with other evidence of renal insufficiencyfailed to show pigment excretion if the urine was tested with benzidinewithin the first 48 hours after injury. Nineteen patients out of the 44,however, who at no time showed any other evidence of renal damage, excretedbenzidine-positive material.
118
Oliguria was demonstrated in 15 patients with 1 or more otherpositive findings. In 3 patients its presence was uncertain and in 6 itwas observed in the absence of any other sign. In one questionable case,in which there was pigment excretion and azotemia, oliguria was absent.Oliguria in these patients who survived was, however, sometimes extremelytransitory. Among the patients manifesting the complete tetrad, oliguriawas of only a day`s duration in two cases, and lasted only 2 days in one.The longest duration of oliguria did not exceed 4 days. In none of thecases was output depressed to anuric levels; i.e., below 100 cc. in 24hours.
Azotemia was observed in 15 of the 44 patients. In no instancewas it the sole finding. A plasma nonprotein nitrogen concentration of88 mg. per 100 cc. accompanied only by pigment excretion occurred in oneinstance. In 7 patients the maximal level was below 100 mg. per 100 cc.,and in 6 the range was between 100 and 150 mg. per 100 cc. of plasma. Twodesperately ill patients recovered despite nonprotein nitrogen levels of247 and 217 mg. per 100 cc. respectively. In 3 patients the azotemia wasof such low degree (74, 77, and 69 mg. per 100 cc. respectively) and sotransitory (lasting only 1 and 2 days) as to be of doubtful significance.In the other patients it lasted from 3 to 21 days.
Seven patients showed definite hypertension which ranged from128/90 in Case 54 to 180/115 in Case 138. Blood pressure was not recordedfor two patients who presented the triad of pigment excretion, oliguria,and azotemia, but did not become elevated in five other patients presentingthe same combination. The remaining two patients in this group had, respectively,azotemia of more than 17 days` duration with a maximum nonprotein nitrogenlevel of 247 mg. per 100 cc., and azotemia of over 7 days`duration witha nonprotein nitrogen level of 140 mg. per 100 cubic centimeters. Hypertensionwas never observed without other evidence of renal insufficiency. Oncehypertension developed it was very persistent, even after the nonproteinnitrogen had dropped to normal levels. The shortest duration of hypertensionobserved was 12 days, and in one patient it was still present at 22 days.
In summary, pigment excretion appeared to be a constant phenomenon inthe shock kidney but was seen also in many patients who never showed evidenceof renal failure. Oliguria likewise was frequently seen in the absenceof renal failure. In positive cases it might be extremely transitory andthe volume not greatly depressed. Azotemia was a constant and, except inthe presence of severe complications or in the moribund state, a reliablesign of renal failure. Eleva-
119
tion of blood pressure in the absence of a head injury was inconstant.When present it constituted the most important confirmatory criterion.
On these grounds it is reasonable to conclude that all seven survivingpatients manifesting hypertension did, in fact, have "shock kidney." Insix of these azotemia was proved, and in the seventh the nonprotein nitrogenlevel was not recorded. Eight other patients showed azotemia supportedby one or more other criteria of renal injury. In three patients azotemiawas so slight and transitory as to be of doubtful significance. In theremainder it was of sufficient severity or was bolstered by enough otherconfirmatory evidence to justify the diagnosis of renal injury.
We conclude, then, that a minimum of 11 and a possible maximum of 14of our patients developed and survived "shock kidney." In comparison with38 fatal cases of histologically proved shock kidney, this indicates acase fatality rate of approximately 75 percent.
SUMMARY AND CONCLUSIONS
The clinical records of 60 patients on whom necropsy was performed wereanalyzed from the standpoint of factors relating to renal function, andthe findings in the group of 38 with histologically demonstrated pigmentnephropathy were compared with those of the 22 in whom this lesion wasnot present. It became apparent that the clinical syndrome of renal insufficiencywhich follows shock is remarkable chiefly for the scarcity and mildnessof its symptoms. Little that the patient complained of served to call attentionto the condition. Drowsiness slowly deepening into stupor was the mostcommon symptom, but it might be absent almost until death. The only commonsign was edema, either pulmonary or peripheral.
Laboratory and blood pressure findings provided more useful criteria.Seven findings were present with great constancy in the nephropathic casesthat appeared only sporadically or never in the control group. These werein ascending order of diagnostic importance: proteinuria, persistent acidityof the urine, excretion of benzidine-positive material, oliguria, azotemia,fixation of specific gravity of the urine at a low level, and hypertension.It was found that the diagnosis of nephropathy could only be made by thesystematic recording of four factors in every patient who was resuscitatedfrom shock: (1) the total urinary output, (2) the presence of benzidine-positivematerial in the urine, (3) the nonprotein
120
nitrogen level in the blood plasma, and (4) the systolic blood pressure.The symptom complex of oliguria, pigment excretion, azotemia, andhypertensionestablished the diagnosis. It is probable that in some cases oliguriawas too transient to be recognizable, and certain that in some cases hypertensiondid not develop. If the patient survived beyond 4 days, fixation of specificgravity and constant acidity of the urine afforded important confirmatoryevidence.
These diagnostic criteria of nephropathy were then applied in a reviewof the records of the nonfatal cases in the series. It was concluded thata minimum of 11 and a possible maximum of 14 had had a pigment nephropathy.Using the former figure, the case fatality rate is approximately 75 percent.
CASES OF SPECIAL INTEREST IN THIS CHAPTER
Nonfatal
13 44 72 109 133
27 54 81 112 138
29 60 87 125 150
37 71 104 130
Fatal
8 26 52 85 108 122
12 31 55 86 116 123
22 41 65 88 117 129
24 47 66 95 118 131
25 49 74 97 120 136
80 98 A-30
Crush Syndrome Fatalities
69 70 78 93 132
