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Renal Papillary Necrosis: Case Report
THE JOURNAL OF UROLOGY
Vol. 68, No. 2, August 1952 Printed in U.S.A.
RENAL PAPILLARY NECROSIS: CASE REPORT ALVIN SLIPYAN
AND
SAMUEL BARLAND
Although this condition was first described by Friedreich1 in 1877, it is only during the past 13 years that definite attempts have been made to separate this disease from pyelonephritis as a distinct clinical entity. Numerous theories as to pathogenesis have been suggested, although none, at the present time, is entirely logical. In 1937, Gunther 2 made an extensive survey of the disease and stressed the association with diabetes mellitus and urinary obstruction and infection. He definitely and conclusively associated diabetes as part of this disease to his m,vn satisfaction. In 1942, Harrison and Bailey3 demonstrated that 50 per cent of diabetics had asymptomatic urinary tract infection. In 1944, Robbins and Tucker4 reported from the Mallory Institute of Pathology, 307 autopsied cases. The cause of death in 6.7 per cent of diabetic patients was pyelonephritis, and most of this group had necrotizing papillitis. In 1946, Robbins, Mallory, and Kinney 5 reported 2.6 more cases from the Mallory Institute of Pathology, Boston City Hospital, and the Peter Bent Brigham Hospital. Nineteen were in diabetics, and seven were in nondiabetics. Evidence of urinary tract obstruction was not found in the diabetics usually, but the nondiabetics always exhibited evidence of chronic obstruction. The degree or duration of the diabetes was no factor in the pathogenesis. The nondiabetics were in men between 61 and 71 years of age. The acute fulminating cases created the most perplexing problems, and many divergent diagnoses were expressed. The authors believed that the necrotizing papillitis was simply a form of acute pyelonephritis; the pathogenesis being the coalescence of small abscesses at the base of the pyramids with distal ischemic infarction. In 1947, Edmonston, Martin, and Evans 6 reviewed the literature once again and reported on 27 cases, proven by autopsy. Here, too, the same pathological lesions were stressed and the same clinical differentiations reported. In 1949, Robbins and Angrist7 reported 14 cases, autopsied at the Queens General Hospital. They classified the disease clinically as acute or subacute. The acute cases occur usually in diabetics with the sudden onset of coma, either with or without acidosis, and generally with azotemia. Pyuria, hematuria, high fever, and leukocytosis were found. The course was rapid and fatal in a few days. The subacute cases were found in: a) Diabetics with pyelonephritis for a few weeks, and who suddenly become worse. 1
von Friedreich, N.: Virch. Arch. f. path. Anat., 69: 308, 1877. Gunther, G. W.: Muchen med. Wochnschr., 84: 1695, 1937. 3 Harrison, J. H. and Bailey, 0. T.: J. A. M.A., 118: 15, 1942. 4 Robbins, S. L. and Tucker, A. W. Jr.: New Eng. J. Med., 231: 865, 1944. 5 Robbins, S. L., Mallory, K. G. and Kinney, T. D.: New Eng. J. Med., 235: 885, 1946. 6 Edmondson, H. A., Martin, H. E. and Evans, N.: Arch. Int. Med., 79: 148, 1947. 7 Robbins, E. D. and Angrist, A.: Necrosis of renal papillae. Ann. Int. Med., 31: 773, 1949. 430 1
2
RENAL PAPILLARY NECROSIS
431
b) Diabetics in whom septicemia developes from some focus of infection, and who are found to have pyuria and azotemia. c) Diabetics with chronic obstruction of the urinary tract, in whom an ascending infection develops with sepsis, azotemia, and resemble suppurative pyelonephritis, without papillary necrosis. During the attack a sloughing papilla will result in renal colic and hematuria, with a defect of the calyces on pyelography, which suggests stone, tumor, or tuberculosis, according to Gunther. 2 In addition to the previous theories of infection, mechanical factors, circulatory disturbances, role of the diabetic state, these authors commented on the parallelism between disturbed fat metabolism in diabetics, and in nondiabetics with chronic urinary tract obstruction with sepsis. In support of this hypothesis they quote the work of Burr and Burr, 8 pertaining to the production of a deficiency of unsaturated long chain fatty acids by a fat free diet in rats. This deficiency can also occur in diabetics. Muirhead, Vanatta, and Grollman9 reported 3 cases of papillary necrosis, and the experimental production of papillary necrosis in dogs by obstructing the ureters of one or both sides. They concluded from the results of their studies in dogs that the papillary necrosis of the kidney was due to an acute obstruction of the urinary tract, and may be produced bilaterally or unilaterally by mechanical means. In diabetics, however, they infer that the interstitial infection is the primary cause. CASE REPORT
A. L., a 54 year old man, was admitted to the Parsons Hospital on September 16, 1949. On the evening of September 14, 1949, after bowling, he suddenly experienced pain in both lower abdominal quadrants, dysuria, frequent urination of small amounts of urine. No blood or pus was noted in the urine at that time. His previous history was not relative. He presumably had healed tuberculosis of the lungs?, an operation for tic douloureux, and the finding of a right bundle branch block on electrocardiography a few months previously. He complained at that time of some precordial pains on exertion, but had no other symptoms referable to the heart. No history of rheumatic fever or other acute illness was elicited. His mother and father had diabetes and 2 brothers also had diabetes, but at no time were abnormal amounts of sugar found in the urine and blood of the patient, although numerous urines and blood examinations were done. Physical examination revealed a well nourished man, apparently in acute distress because of pain in the right lower abdominal quadrant. No nausea, vomiting, diarrhea, constipation, cyanosis, jaundice, nor respiratory distress was noted. The skin was dry and cool. The head and neck revealed no abnormalities. The heart percussed normally and the tones were of fair quality, regular, 72/min. with no audible murmurs. The lungs percussed normally and the sounds were physiological and no rales were heard. The abdomen was soft but definitely tender in the right lower quadrant with an equivocal peritoneal res Burr, G. 0. and Burr, M. M.: J. Biol. Chem., 87: 345, 1929. Muirhead, E. E., Vanatta, J. and Grollman, A.: J. A. M.A., 142: 627, 1950.
9
432
ALVIN SLIPYAN AND SAMUEL BARLAND
bound. The right Murphy sign was 2 plus. Reflexes were physiological. Temperature was 99F rectally. A diagnosis of right ureteral obstruction, probably calculus, was made, and the patient was referred to the urological department. Urinalysis, cystoscopy, pyelography, both excretory and retrograde, revealed no unusual features. Three hours following the cystoscopic examination, the patient became feverish. His temperature was 104F and his pulse became very rapid. He did not pass any urine during the next 18 hours, and a repeat cystoscopy was performed at 1 a.m. on September 17, 1949. At this examination a large blood clot was seen protruding from the left ureter and no urine could be obtained from the right ureter. The clot was removed and the patient began to excrete urine again. A blood count on admission revealed a leukocytosis of 13,350 with 75 per cent polymorphonuclears and 25 per cent lymphocytes, 4.5 million red blood cells and 15 gm. hemoglobin. Following the episode of acute renal suppression, the urea nitrogen was 50 mg. per cent and the nonprotein nitrogen 100 mg. per cent. The blood sugar was 112 mg. per cent. Since the fever did not abate and the symptoms of anuria persisted, another cystoscopic examination was performed and indwelling ureteral catheters inserted. The day following this procedure, the urea nitrogen dropped to 23 mg. per cent. Although the urine was now draining adequately, the patient appeared worse. His face was flushed and pinched. He kept complaining constantly of right abdominal pains. He was now vomiting and had a persistent diarrhea. There was definite right abdominal tenderness and spasticity with a positive rebound phenomenon. Another urologist who was consulted thought that the patient had some intra-abdominal disease. A medical consultant concurred in this opinion, and stated that the trouble was not in the kidneys. On September 23, 1949, one week after admission, a blood culture was positive for B. coli. A urine culture was also positive for B. coli. The patient had become jaundiced and coarse rales were present at both lung bases. The abdomen was still tender on the right side with persistent peritoneal rebound. A chest film was interpreted as within normal limits. Surgical consultation advised waiting and the continued use of penicillin, streptomycin and aureomycin therapy. The patient improved and the jaundice subsided and repeated blood cultures were negative. Patient was given intravenous fluids and protein, and blood transfusions. The pain in the right abdomen persisted with peritoneal rebound, in spite of the marked general improvement. The temperature remained elevated and continued to spike. An exploratory laparotomy was done on September 28, 1949. No evidence of any intra-abdominal disease was found. A needle biopsy of the right kidney was reported as negative. Following the operation the patient seemed to improve. But on October 3, 1949, he suddenly became irrational; he responded to orders but appeared quite detached from his surroundings. The left pupil was smaller than the right but reacted well to light. The swallowing mechanism was disturbed. Definite nuchal rigidity was present. The heart was rapid with a loud systolic murmur at the
RENAL PAPILLARY NECROSIS
433
apex transmitted over the precordium. Lungs were clear. A diagnosis was made of uremia and blood chemistry again revealed an elevated urea nitrogen and a positive blood culture for B. coli. Death occurred October 3, 1949. Autopsy: On gross examination both kidneys were found similar in size and their combined weight was 350 gm. The capsules were easily stripped and revealed smooth cortical surfaces. On the posterior surface of the left kidney there was a match-head sized cortical abscess. Adjacent to this area the peripelvic fat was found covered by a patch of brownish fibrinous exudate. The cut surfaces of each kidney presented a remarkable appearance. Each pyramid had a yellowish opaque texture and was covered by a narrow rim of green tissue measuring 1 mm. in width. Beyond this there was a zone of hyperemia which quickly faded as it extended toward the periphery of the kidney. The perfectly constant anatomic distribution, symmetry and sharp delimitation of the morbid
FrG. 1. a, Yellow necrotic area of pyramid. b, Zone of leukocytic infiltration. c, Zone of congestion.
pathology to the pyramids was most impressive. The papillae were slightly irregular and granular, but no definite sloughing could be demonstrated. Several pinhead sized abscesses were scattered irregularly throughout the cortex, but with the exception of the lesion described previously in the left kidney none had penetrated through the capsule. The pelves and calyces were somewhat dilated and contained a turbid odorless fluid. The histology was almost schematic in its uniformity and the sharp division of anatomic changes. The pyramids showed a complete ischemic necrosis with the original architecture represented by a faint but distinct outline. The greenish layer described grossly was found to consist of neutrophiles. The hyperemic area consisted of congested vessels. Bacterial stains showed gram negative rods limited almost entirely to the suppurative layer and the papillae (fig. 1). The gross tissue and sections were submitted to Dr. Alfred Angrist who commented that it was the most perfect and exquisite example of papillary necrosis that he had seen.
434
ALVIN SLIPYAN AND SAMUEL BARLAND
The remainder of the findings consisted of multiple miliary abscesses of the lungs. COMMENT
The primary function of any medical scientific investigation is the separation and classification of clinical and pathological entities. However, it will be observed in reading the literature that there is a definite reluctance in regarding papillary necrosis as a specific disease. The tendency is to imply that the distinctive and peculiar alteration in structure encountered in this condition is a form or progression of pyelonephritis. The basis of this hesitancy is produced by the fact that the lesion produced in these cases is not consistent with our present knowledge of the anatomic structure of the kidney. In essence we find multiple areas of ischemic infarction, limited to the conical renal pyramids, surrounded by a zone of leukocytic reaction. This type of alteration in structure is one of the oldest described patterns in pathological anatomy. The pathogenesis of this state has been attributed to vascular occlusion, either mechanical or spastic, supplying the affected area. The difficulty, at present, consists in our inability to demonstrate any vascular system whose sole and only function is to supply the pyramids and the occlusion of which would result in the observed lesion. The view advanced by Robbins, Mallory and Kinney 5 is that small abscesses form at the corticomedullary junction which by coalescence result in vascular obstruction and subsequent infarction. It would, however, be most difficult to explain by what route the bacteria reached this selective site of localization, and were limited practically exclusively to this site. Certainly neither septicemia nor ascending pyelonephritis can be suggested as an adequate explanation, since neither of these processes involve this area exclusively. Furthermore it could be reasonably expected that at least in some instances the early stages of such a process could be demonstrated. Robbins and Angrist 7 commented that the pathogenesis is related to the abnormal fat metabolism. That such abnormal chemical physiology exists in diabetics is not disputed. However it must be kept in mind that many abnormal chemical changes in diabetics exist, for example, a marked increase of glycogen in the renal tubules. The simultaneous occurrence of multiple abnormalities does not necessarily indicate that there is a causal relationship. Furthermore it has been clearly demonstrated that the condition is not related to the duration or severity of the diabetes. 5 It is, of course, apparent that in the considerable group of cases not associated with diabetes, the concept would be entirely inapplicable. Our criticism of this postulation is not to be construed as denying a relationship between diabetes and papillary necrosis, but as suggesting that this relationship is at present obscure and not an essential factor. The third explanation offered is based on the mechanism of either acute or chronic urinary obstruction. The arguments in support of this theory are based on experimental lesions produced in dogs by ureteral ligation. 9 The deductions drawn from such experimentation must be applied to human material with great caution as must the results of all animal experimentation. The lesions
RENAL PAPILLARY NECROSIS
435
produced as described by the authors, have only a superficial resemblance, and at times are completely unlike those found in papillary necrosis. Perhaps it would avoid confusion if the terminology were corrected since the disease is one of pyramidal necrosis. Papillary necrosis is a descriptive term of a type of pathologic alteration which is most frequently found as a complication of renal tuberculosis or nonspecific pyelitis and may occur in this disease. The lesion described in the animals is chiefly one of internal tubular hydronephrosis complicated by suppurative infection and streaked abscesses extending into the cortex. The lesion we are considering is one of ischemic coagulative necrosis of the pyramids bordered by a zone of reaction characteristic of all infarcts, the cortical involvement being entirely incidental and the result of old injuries or miliary abscesses as may occur in any septicemia. In our case many more foci of seeding were found in the lung parenchyma than in the kidney cortex. Furthermore, the authors concede that this mechanism would be entirely inadequate to explain the frequent association with diabetes, the usual bilateral distribution of the lesion and those cases not complicated by pyelitis or obstruction. From a statistical point of view it would also be quite strange that papillary necrosis is so rare though pyelitis and obstructive uropathy are very common. It was the homologue of this very same problem, bilateral cortical necrosis, that stimulated Trueta10 and his colleagues in the search for the vascular shunts for the efferent paraglomerular vessels, since the anatomic distribution of cortical necrosis could be explained only by postulating that such shunts did, in fact, exist. It is, however, apparent that this demonstration of a dual vascular supply to the medulla both from the efferent and afferent vessels of the glomerulus can in no way be used to elucidate the mechanism of pyramidal infarction. vVe are, therefore, faced with the dilemma of having no adequate anatomical basis for the lesion. The case we have presented, representing the occurrence of this lesion in a relatively young, well nourished, nondiabetic subject, with no evidence of any previous genito-urinary disturbance, provoked our curiosity and caused us to question the validity of the previous assumptions. Although we can offer no complete explanation of the pathogenesis of the disease, there are certain features which we believe have a significant relationship. Embryologically the kidney is formed by the fusion of the serrated cap of nephrogenic tissue from the dorsal wall with the grooved mass of metanephros extending cephalad from the bladder. These two structures of different origin carry along with them their individual nerve supply and the failure of this fusion results in various well known congenital anomalies. The nephrogenic tissue forms the cortex and columns of Bertin, while the metanephros forms the ureter, pelvis, calyxes and series of conical masses known as the pyramids.11 It appears to us more than accidental that some disease processes such as 10 11
Trueta, J. et al.: Studies of the Renal Circulation. Oxford: Blackwell, 1947, p. 187. Patton, B. M.: Human Embryology. Philadelphia: Blakiston, 1946, p. 559.
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ALVIN SLIPYAN AND SAMUEL BARLAND
bilateral cortical necrosis are limited almost entirely to tissue derived from the nephrogenic tissue, while others such as papillary necrosis are limited to the structures derived from the metanephros. Many other renal lesions show a peculiar limitation of distribution, not readily explained, such as glomerular nephritis and nephrosis. The observation that there is some overlapping of lesions is not inconsistent with the hypothesis of different function and response of these separately derived segments of tissue which on fusion form the kidney organ. It is apparent by analogy to such organs as the adrenal and pancreas, which are composed of tissues of totally different origin and function, that an infectious process, which involves one portion of the structure will by progression affect contiguous areas. It is also possible, in so far as the kidney is concerned, to demonstrate its dual character by experimental methods. The intraperitoneal injections of adrenalin results in spasm of the cortical vessels, the medullary vessels being uninvolved. 11 In the experimental investigations of the Schwartzman reaction by protein injections, the production of bilateral cortical necrosis is one of the most constant and distinctive features. 12 It is our belief that this different approach may serve to lead us to a clearer understanding of both the pathogenesis and pathology of renal disease. Although the case we have presented is unusual in many respects, these very features should act as a test of the validity of our previous assumption.
5501 Van Horn St., Elmhurst, N. Y. 12
Schwartzman, G.: J. Mt. Sinai Hosp., 16: 207, 1949.
Vol. 68, No. 2, August 1952 Printed in U.S.A.
RENAL PAPILLARY NECROSIS: CASE REPORT ALVIN SLIPYAN
AND
SAMUEL BARLAND
Although this condition was first described by Friedreich1 in 1877, it is only during the past 13 years that definite attempts have been made to separate this disease from pyelonephritis as a distinct clinical entity. Numerous theories as to pathogenesis have been suggested, although none, at the present time, is entirely logical. In 1937, Gunther 2 made an extensive survey of the disease and stressed the association with diabetes mellitus and urinary obstruction and infection. He definitely and conclusively associated diabetes as part of this disease to his m,vn satisfaction. In 1942, Harrison and Bailey3 demonstrated that 50 per cent of diabetics had asymptomatic urinary tract infection. In 1944, Robbins and Tucker4 reported from the Mallory Institute of Pathology, 307 autopsied cases. The cause of death in 6.7 per cent of diabetic patients was pyelonephritis, and most of this group had necrotizing papillitis. In 1946, Robbins, Mallory, and Kinney 5 reported 2.6 more cases from the Mallory Institute of Pathology, Boston City Hospital, and the Peter Bent Brigham Hospital. Nineteen were in diabetics, and seven were in nondiabetics. Evidence of urinary tract obstruction was not found in the diabetics usually, but the nondiabetics always exhibited evidence of chronic obstruction. The degree or duration of the diabetes was no factor in the pathogenesis. The nondiabetics were in men between 61 and 71 years of age. The acute fulminating cases created the most perplexing problems, and many divergent diagnoses were expressed. The authors believed that the necrotizing papillitis was simply a form of acute pyelonephritis; the pathogenesis being the coalescence of small abscesses at the base of the pyramids with distal ischemic infarction. In 1947, Edmonston, Martin, and Evans 6 reviewed the literature once again and reported on 27 cases, proven by autopsy. Here, too, the same pathological lesions were stressed and the same clinical differentiations reported. In 1949, Robbins and Angrist7 reported 14 cases, autopsied at the Queens General Hospital. They classified the disease clinically as acute or subacute. The acute cases occur usually in diabetics with the sudden onset of coma, either with or without acidosis, and generally with azotemia. Pyuria, hematuria, high fever, and leukocytosis were found. The course was rapid and fatal in a few days. The subacute cases were found in: a) Diabetics with pyelonephritis for a few weeks, and who suddenly become worse. 1
von Friedreich, N.: Virch. Arch. f. path. Anat., 69: 308, 1877. Gunther, G. W.: Muchen med. Wochnschr., 84: 1695, 1937. 3 Harrison, J. H. and Bailey, 0. T.: J. A. M.A., 118: 15, 1942. 4 Robbins, S. L. and Tucker, A. W. Jr.: New Eng. J. Med., 231: 865, 1944. 5 Robbins, S. L., Mallory, K. G. and Kinney, T. D.: New Eng. J. Med., 235: 885, 1946. 6 Edmondson, H. A., Martin, H. E. and Evans, N.: Arch. Int. Med., 79: 148, 1947. 7 Robbins, E. D. and Angrist, A.: Necrosis of renal papillae. Ann. Int. Med., 31: 773, 1949. 430 1
2
RENAL PAPILLARY NECROSIS
431
b) Diabetics in whom septicemia developes from some focus of infection, and who are found to have pyuria and azotemia. c) Diabetics with chronic obstruction of the urinary tract, in whom an ascending infection develops with sepsis, azotemia, and resemble suppurative pyelonephritis, without papillary necrosis. During the attack a sloughing papilla will result in renal colic and hematuria, with a defect of the calyces on pyelography, which suggests stone, tumor, or tuberculosis, according to Gunther. 2 In addition to the previous theories of infection, mechanical factors, circulatory disturbances, role of the diabetic state, these authors commented on the parallelism between disturbed fat metabolism in diabetics, and in nondiabetics with chronic urinary tract obstruction with sepsis. In support of this hypothesis they quote the work of Burr and Burr, 8 pertaining to the production of a deficiency of unsaturated long chain fatty acids by a fat free diet in rats. This deficiency can also occur in diabetics. Muirhead, Vanatta, and Grollman9 reported 3 cases of papillary necrosis, and the experimental production of papillary necrosis in dogs by obstructing the ureters of one or both sides. They concluded from the results of their studies in dogs that the papillary necrosis of the kidney was due to an acute obstruction of the urinary tract, and may be produced bilaterally or unilaterally by mechanical means. In diabetics, however, they infer that the interstitial infection is the primary cause. CASE REPORT
A. L., a 54 year old man, was admitted to the Parsons Hospital on September 16, 1949. On the evening of September 14, 1949, after bowling, he suddenly experienced pain in both lower abdominal quadrants, dysuria, frequent urination of small amounts of urine. No blood or pus was noted in the urine at that time. His previous history was not relative. He presumably had healed tuberculosis of the lungs?, an operation for tic douloureux, and the finding of a right bundle branch block on electrocardiography a few months previously. He complained at that time of some precordial pains on exertion, but had no other symptoms referable to the heart. No history of rheumatic fever or other acute illness was elicited. His mother and father had diabetes and 2 brothers also had diabetes, but at no time were abnormal amounts of sugar found in the urine and blood of the patient, although numerous urines and blood examinations were done. Physical examination revealed a well nourished man, apparently in acute distress because of pain in the right lower abdominal quadrant. No nausea, vomiting, diarrhea, constipation, cyanosis, jaundice, nor respiratory distress was noted. The skin was dry and cool. The head and neck revealed no abnormalities. The heart percussed normally and the tones were of fair quality, regular, 72/min. with no audible murmurs. The lungs percussed normally and the sounds were physiological and no rales were heard. The abdomen was soft but definitely tender in the right lower quadrant with an equivocal peritoneal res Burr, G. 0. and Burr, M. M.: J. Biol. Chem., 87: 345, 1929. Muirhead, E. E., Vanatta, J. and Grollman, A.: J. A. M.A., 142: 627, 1950.
9
432
ALVIN SLIPYAN AND SAMUEL BARLAND
bound. The right Murphy sign was 2 plus. Reflexes were physiological. Temperature was 99F rectally. A diagnosis of right ureteral obstruction, probably calculus, was made, and the patient was referred to the urological department. Urinalysis, cystoscopy, pyelography, both excretory and retrograde, revealed no unusual features. Three hours following the cystoscopic examination, the patient became feverish. His temperature was 104F and his pulse became very rapid. He did not pass any urine during the next 18 hours, and a repeat cystoscopy was performed at 1 a.m. on September 17, 1949. At this examination a large blood clot was seen protruding from the left ureter and no urine could be obtained from the right ureter. The clot was removed and the patient began to excrete urine again. A blood count on admission revealed a leukocytosis of 13,350 with 75 per cent polymorphonuclears and 25 per cent lymphocytes, 4.5 million red blood cells and 15 gm. hemoglobin. Following the episode of acute renal suppression, the urea nitrogen was 50 mg. per cent and the nonprotein nitrogen 100 mg. per cent. The blood sugar was 112 mg. per cent. Since the fever did not abate and the symptoms of anuria persisted, another cystoscopic examination was performed and indwelling ureteral catheters inserted. The day following this procedure, the urea nitrogen dropped to 23 mg. per cent. Although the urine was now draining adequately, the patient appeared worse. His face was flushed and pinched. He kept complaining constantly of right abdominal pains. He was now vomiting and had a persistent diarrhea. There was definite right abdominal tenderness and spasticity with a positive rebound phenomenon. Another urologist who was consulted thought that the patient had some intra-abdominal disease. A medical consultant concurred in this opinion, and stated that the trouble was not in the kidneys. On September 23, 1949, one week after admission, a blood culture was positive for B. coli. A urine culture was also positive for B. coli. The patient had become jaundiced and coarse rales were present at both lung bases. The abdomen was still tender on the right side with persistent peritoneal rebound. A chest film was interpreted as within normal limits. Surgical consultation advised waiting and the continued use of penicillin, streptomycin and aureomycin therapy. The patient improved and the jaundice subsided and repeated blood cultures were negative. Patient was given intravenous fluids and protein, and blood transfusions. The pain in the right abdomen persisted with peritoneal rebound, in spite of the marked general improvement. The temperature remained elevated and continued to spike. An exploratory laparotomy was done on September 28, 1949. No evidence of any intra-abdominal disease was found. A needle biopsy of the right kidney was reported as negative. Following the operation the patient seemed to improve. But on October 3, 1949, he suddenly became irrational; he responded to orders but appeared quite detached from his surroundings. The left pupil was smaller than the right but reacted well to light. The swallowing mechanism was disturbed. Definite nuchal rigidity was present. The heart was rapid with a loud systolic murmur at the
RENAL PAPILLARY NECROSIS
433
apex transmitted over the precordium. Lungs were clear. A diagnosis was made of uremia and blood chemistry again revealed an elevated urea nitrogen and a positive blood culture for B. coli. Death occurred October 3, 1949. Autopsy: On gross examination both kidneys were found similar in size and their combined weight was 350 gm. The capsules were easily stripped and revealed smooth cortical surfaces. On the posterior surface of the left kidney there was a match-head sized cortical abscess. Adjacent to this area the peripelvic fat was found covered by a patch of brownish fibrinous exudate. The cut surfaces of each kidney presented a remarkable appearance. Each pyramid had a yellowish opaque texture and was covered by a narrow rim of green tissue measuring 1 mm. in width. Beyond this there was a zone of hyperemia which quickly faded as it extended toward the periphery of the kidney. The perfectly constant anatomic distribution, symmetry and sharp delimitation of the morbid
FrG. 1. a, Yellow necrotic area of pyramid. b, Zone of leukocytic infiltration. c, Zone of congestion.
pathology to the pyramids was most impressive. The papillae were slightly irregular and granular, but no definite sloughing could be demonstrated. Several pinhead sized abscesses were scattered irregularly throughout the cortex, but with the exception of the lesion described previously in the left kidney none had penetrated through the capsule. The pelves and calyces were somewhat dilated and contained a turbid odorless fluid. The histology was almost schematic in its uniformity and the sharp division of anatomic changes. The pyramids showed a complete ischemic necrosis with the original architecture represented by a faint but distinct outline. The greenish layer described grossly was found to consist of neutrophiles. The hyperemic area consisted of congested vessels. Bacterial stains showed gram negative rods limited almost entirely to the suppurative layer and the papillae (fig. 1). The gross tissue and sections were submitted to Dr. Alfred Angrist who commented that it was the most perfect and exquisite example of papillary necrosis that he had seen.
434
ALVIN SLIPYAN AND SAMUEL BARLAND
The remainder of the findings consisted of multiple miliary abscesses of the lungs. COMMENT
The primary function of any medical scientific investigation is the separation and classification of clinical and pathological entities. However, it will be observed in reading the literature that there is a definite reluctance in regarding papillary necrosis as a specific disease. The tendency is to imply that the distinctive and peculiar alteration in structure encountered in this condition is a form or progression of pyelonephritis. The basis of this hesitancy is produced by the fact that the lesion produced in these cases is not consistent with our present knowledge of the anatomic structure of the kidney. In essence we find multiple areas of ischemic infarction, limited to the conical renal pyramids, surrounded by a zone of leukocytic reaction. This type of alteration in structure is one of the oldest described patterns in pathological anatomy. The pathogenesis of this state has been attributed to vascular occlusion, either mechanical or spastic, supplying the affected area. The difficulty, at present, consists in our inability to demonstrate any vascular system whose sole and only function is to supply the pyramids and the occlusion of which would result in the observed lesion. The view advanced by Robbins, Mallory and Kinney 5 is that small abscesses form at the corticomedullary junction which by coalescence result in vascular obstruction and subsequent infarction. It would, however, be most difficult to explain by what route the bacteria reached this selective site of localization, and were limited practically exclusively to this site. Certainly neither septicemia nor ascending pyelonephritis can be suggested as an adequate explanation, since neither of these processes involve this area exclusively. Furthermore it could be reasonably expected that at least in some instances the early stages of such a process could be demonstrated. Robbins and Angrist 7 commented that the pathogenesis is related to the abnormal fat metabolism. That such abnormal chemical physiology exists in diabetics is not disputed. However it must be kept in mind that many abnormal chemical changes in diabetics exist, for example, a marked increase of glycogen in the renal tubules. The simultaneous occurrence of multiple abnormalities does not necessarily indicate that there is a causal relationship. Furthermore it has been clearly demonstrated that the condition is not related to the duration or severity of the diabetes. 5 It is, of course, apparent that in the considerable group of cases not associated with diabetes, the concept would be entirely inapplicable. Our criticism of this postulation is not to be construed as denying a relationship between diabetes and papillary necrosis, but as suggesting that this relationship is at present obscure and not an essential factor. The third explanation offered is based on the mechanism of either acute or chronic urinary obstruction. The arguments in support of this theory are based on experimental lesions produced in dogs by ureteral ligation. 9 The deductions drawn from such experimentation must be applied to human material with great caution as must the results of all animal experimentation. The lesions
RENAL PAPILLARY NECROSIS
435
produced as described by the authors, have only a superficial resemblance, and at times are completely unlike those found in papillary necrosis. Perhaps it would avoid confusion if the terminology were corrected since the disease is one of pyramidal necrosis. Papillary necrosis is a descriptive term of a type of pathologic alteration which is most frequently found as a complication of renal tuberculosis or nonspecific pyelitis and may occur in this disease. The lesion described in the animals is chiefly one of internal tubular hydronephrosis complicated by suppurative infection and streaked abscesses extending into the cortex. The lesion we are considering is one of ischemic coagulative necrosis of the pyramids bordered by a zone of reaction characteristic of all infarcts, the cortical involvement being entirely incidental and the result of old injuries or miliary abscesses as may occur in any septicemia. In our case many more foci of seeding were found in the lung parenchyma than in the kidney cortex. Furthermore, the authors concede that this mechanism would be entirely inadequate to explain the frequent association with diabetes, the usual bilateral distribution of the lesion and those cases not complicated by pyelitis or obstruction. From a statistical point of view it would also be quite strange that papillary necrosis is so rare though pyelitis and obstructive uropathy are very common. It was the homologue of this very same problem, bilateral cortical necrosis, that stimulated Trueta10 and his colleagues in the search for the vascular shunts for the efferent paraglomerular vessels, since the anatomic distribution of cortical necrosis could be explained only by postulating that such shunts did, in fact, exist. It is, however, apparent that this demonstration of a dual vascular supply to the medulla both from the efferent and afferent vessels of the glomerulus can in no way be used to elucidate the mechanism of pyramidal infarction. vVe are, therefore, faced with the dilemma of having no adequate anatomical basis for the lesion. The case we have presented, representing the occurrence of this lesion in a relatively young, well nourished, nondiabetic subject, with no evidence of any previous genito-urinary disturbance, provoked our curiosity and caused us to question the validity of the previous assumptions. Although we can offer no complete explanation of the pathogenesis of the disease, there are certain features which we believe have a significant relationship. Embryologically the kidney is formed by the fusion of the serrated cap of nephrogenic tissue from the dorsal wall with the grooved mass of metanephros extending cephalad from the bladder. These two structures of different origin carry along with them their individual nerve supply and the failure of this fusion results in various well known congenital anomalies. The nephrogenic tissue forms the cortex and columns of Bertin, while the metanephros forms the ureter, pelvis, calyxes and series of conical masses known as the pyramids.11 It appears to us more than accidental that some disease processes such as 10 11
Trueta, J. et al.: Studies of the Renal Circulation. Oxford: Blackwell, 1947, p. 187. Patton, B. M.: Human Embryology. Philadelphia: Blakiston, 1946, p. 559.
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bilateral cortical necrosis are limited almost entirely to tissue derived from the nephrogenic tissue, while others such as papillary necrosis are limited to the structures derived from the metanephros. Many other renal lesions show a peculiar limitation of distribution, not readily explained, such as glomerular nephritis and nephrosis. The observation that there is some overlapping of lesions is not inconsistent with the hypothesis of different function and response of these separately derived segments of tissue which on fusion form the kidney organ. It is apparent by analogy to such organs as the adrenal and pancreas, which are composed of tissues of totally different origin and function, that an infectious process, which involves one portion of the structure will by progression affect contiguous areas. It is also possible, in so far as the kidney is concerned, to demonstrate its dual character by experimental methods. The intraperitoneal injections of adrenalin results in spasm of the cortical vessels, the medullary vessels being uninvolved. 11 In the experimental investigations of the Schwartzman reaction by protein injections, the production of bilateral cortical necrosis is one of the most constant and distinctive features. 12 It is our belief that this different approach may serve to lead us to a clearer understanding of both the pathogenesis and pathology of renal disease. Although the case we have presented is unusual in many respects, these very features should act as a test of the validity of our previous assumption.
5501 Van Horn St., Elmhurst, N. Y. 12
Schwartzman, G.: J. Mt. Sinai Hosp., 16: 207, 1949.