0022-5347/78/1201-0106$02. 00/0 Vol. 120, July Printed in U.SA.
THE JOURNAL OF UROLOGY
Copyright © 1978 by The Williams & Wilkins Co.
Clinicopathologi cal Conference COMA AND HYPERCHLOREMIC ACIDOSIS JAMES MANDELL*
AND
FLOYD A. FRIEDt
From the Department of Surgery, Division of Urology, The University of North Carolina School of Medicine, Chapel Hill, North Carolina
PRESENTATION OF CASE:j:
Dr. James Mandell. A 43-year-old black woman was admitted to a local hospital in a comatose state. This condition had been preceded by a 2-day history of extreme lethargy, unresponsiveness and poor oral alimentation. The patient apparently had been without complaints, other than headaches, for 3 days before the onset of the stuporous state. There was no history of drug or alcohol ingestion, head or other trauma, seizures, hypertension, fever or renal disease. Pertinent physical findings on that hospitalization included blood pressure 150/90 mm. Hg, pulse 76, respiration 18 and temperature •100.4C. The patient was lethargic and uncommunicative but moved all extremities. The neck was supple. Chest, heart and abdominal examinations were normal. Neurologic examination revealed no other localizing signs. The hematocrit was 34 per cent, white blood count 5,000/mm. 3 with 70 per cent segmented neutrophils and urinalysis was normal except for a specific gravity of 1.009 and occasional rod-shaped bacteria. The serum sodium was 131 mEq./1., potassium 3.9 mEq./1., chloride 108 mEq./1. and phosphorus 5 mg. per cent. An SMA-12 survey was normal. The blood urea nitrogen was 82 mg. per cent, alkaline phosphatase 95 units and lactic dehydrogenase 204 units. Stool for occult blood was negative. Skull and chest x-rays were within normal limits. A lumbar puncture showed an opening pressure of 300 mm. water, with clear fluid that was microscopically negative. The patient was referred to our hospital. Physical findings when the patient was admitted to this institution remained unchanged except for the questionable appearance of blurred optic disks bilaterally. The medical history was unremarkable except for an operation 1¼ years earlier for internal drainage of a pancreatic pseudocyst. Admission laboratory data revealed serum sodium 151 mEq./1., potassium 3.5 mEq./1., chloride greater than 130 mEq./1., carbon dioxide 8 mEq./1., blood urea nitrogen 70 mg. per cent, creatinine 1.4 mg. per cent, glucose 100 mg. per cent, calcium 8.5 mg. per cent and phosphorus 3.1 mg. per cent. The serum bromide level was 7 mEq./1. and the salicylate level was 5 mg. per cent. Blood gases revealed an arterial oxygen pressure of 97 mm. Hg, carbon dioxide pressure 17 mm. Hg and a pH of 7.20. An initial electrocardiogram demonstrated 10 to 12 premature ventricular contractions but a repeat study the next day was normal. Urinalysis showed a pH of 6.0, greater than 50 red blood cells per high power field, 2 plus proteinuria and a specific gravity of 1.009. Upon the advice of a neurological consultant a right carotid arteriogram was performed on the night of admission to the hospital and was normal. Urine culture on the day of hospitalization yielded greater than 100,000 Escherichia coli and a blood culture was negative.
* Fellow in Pediatric Urology, University of North Carolina at Chapel Hill. t Professor of Surgery, Chief of Urology, University of North Carolina at Chapel Hill. :j: Case presented at Urological Grand Rounds University of North Carolina at Chapel Hill, on October 13, 1977. '
Hydration, alkalization and potassium supplementation returned the patient to an alert conscious state within 12 hours. Questioning of the patient at this time revealed that she had not been taking medication other than an occasional analgesic for headaches. She reported that she had been in good health until the abdominal operation 18 months earlier. Since that time she had noticed progressive weakness, weight loss, anorexia and diarrhea. After correction of the initial electrolyte and fluid imbalance the serum electrolytes remained normal with the exception that the woman required persistent bicarbonate supplementation to prevent return of acidosis. After the patient had been hospitalized 3 days the serum creatinine value stabilized at 1.3 mg. per cent, with a blood urea nitrogen of 50 mg. per cent. Further neurologic evaluation, including an electroencephalogram and repeat lumbar puncture, were non-revealing. The woman was treated with ampicillin for the E. coli urinary tract infection and urologic consultation was obtained. DIFFERENTIAL DIAGNOSIS
Dr. Floyd A. Fried. An extensive neurologic evaluation had been performed without revealing the etiology of the coma. There was no apparent central nervous system lesion or underlying septicemia. The fact that the sensorium cleared rapidly after correction of the metabolic acidosis suggests that the stuporous state was secondary to the fluid and electrolyte imbalances. The essentials of the problem are a patient with mild renal insufficiency and hyperchloremic acidosis. Causes for hyperchloremic acidosis can be divided into 5 major categories: 1) renal tubular diseases, 2) ingestion of exogenous agents, 3) lactic or diabetic acidosis, 4) chronic diarrheal states and 5) urinary enteric fistulas. With regard to primary renal tubular acido:;;is, the form of the disorder seen in adults predominates in women. There is significant loss of potassium in the urine to the point at which periodic paralysis may be seen. 1 The 24-hour excretion of potassium in this case was a modest 9 mEq./1. , which would make this diagnosis unlikely. Other renal tubular problems, such as oculocerebrorenal dystrophy (Lowe's syndrome), which is associated with congenital glaucoma, cataracts, mental retardation and rickets, 2 and consumption of large amounts of calcium cyclamate, which has been reported to produce a reversible form of renal tubular acidosis, 3 can be eliminated since neither of these entities applyies to our patient. Chronic ingestion of therapeutic doses of salicylates can produce a respiratory alkalosis through direct stimulation of the medullary respiratory center. This results in hyperventilation with a subsequent fall in carbon dioxide pressure. These changes ensue when plasma salicylate levels are in the range of 35 mg. per cent. Toxic doses of salicylates can produce a severe metabolic acidosis. 4 However, the salicylate level in this patient was 5 mg. per cent, effectively eliminating this as a possibility. Although the serum bromide was elevated moderately, levels less than 10 mEq./1. should not alter the
106
107 sensorium nor this of acidosis. questioning of patient is to have failed to any other exogenous agents that were ingested and could produce a state of acidosis. Various clinical entities that produce shock are associated with a lactic acidosis. This patient had no findings suggesting shock. An electrocardiogram and vital signs were normal. Although the hematocrit was 34 per cent there was no suggestion of acute blood loss. A blood culture revealed no growth. All of these data indicate that the acidosis was not secondary to shock. Diabetic acidosis also is eliminated from consideration with the findings of normal blood sugar levels. Chronic diarrheal states can result in depletion of sodium, potassium and bicarbonate with the development of a hyperchlorernia. The patient reported that she had long-standing diarrhea, which had developed since the operation 18 months earlier. Persistent diarrhea of this degree of severity with resultant acidosis brings to mind inflammatory bowel disease, neoplasia and villous adenoma. The only data we are afforded concerning the bowel is that the stool contained no blood. In view of the paucity of data I believe that it is likely that the chronic diarrhea certainly is aggravating the acidosis but it appears unlikely that it is the primary problem. Thus, the obvious causes for acidosis, renal tubular disease, exogenous agents, diabetes, shock and primary bowel disease seem to be unlikely. A review of the history revealed that 1½
earlier the had had a internally a of small The 1-1u,o;,,iu111uv that a fistula had been created inadvertently between urinary tract and small intestine is intriguing. A urinary enteric fistula could explain the development of chronic diarrhea with hyperchloremic acidosis. Of the renal problems that could be mistaken for pancreatic pseudocyst, a large renal cyst or distended renal pelvis com.es to mind. Since most renal cysts have no significant communication with the renal collecting system I would favor the diagnosis of a large hydronephrotic renal pelvis, perhaps secondary to congenital ureteropelvic junction obstruction with an iatrogenic fistula to the small bowel. The creation of such a fistula would result in increased fluid loss with loss of sodium, potassium and bicarbonate. The large amount of urea entering the bowel would further explain the elevated blooC: urea nitrogen with a near normal serum creatinine. DISCUSSANTS' DIAGNOSES
Stupor secondary to metabolic acidosis. Hyperchloremic acidosis secondary to chronic diarrhea state with possible urinary enteric fistula as underlying source. DISCUSSION OF FINDINGS AND SURGERY
Doctor Mandell. An excretory urogram (IVP) demonstrated bilateral pyelocaliectasis. Gradual opacification of the small
Fm. 1. A, IVP reveals bilateral pyelocaliectasis, worse on right side, with contrast medium seen in small intestine (arrow). B, left retrograde pyelogram reveals ureteropelvicjunction obstruction and communication between renal pelvis and small intestine (arrow).
Fm. 2. A, photomicrograph of intestinal epithelium demonstrates Brunner's glands with edema and inflammation of mucosa. B, photomicrograph of renal pelvis demonstrates diffuse edema and chronic inflammation.
CLINICOPATHOLOGICAL CONFERENCE
108
bowel was noted. A retrograde pyelogram of the left upper tract demonstrated a ureteropelvic junction obstruction and a left urinary enteric fistula (fig. 1). Left pyeloplasty and takedown of the fistulous tract were performed and, subsequently, a right pyeloplasty was performed without event. DISCUSSION OF PATHOLOGY
Dr. Charles N. Carney. The surgically resected specimen consisted of a segment of small intestine and attached renal pelvis. The intestinal tissue has mucosal glands lined by tall columnar intestinal epithelium with goblet cells and columnar epithelium like that of the Brunner's glands with flattened basal nuclei and granular acidophilic cytoplasm. There is focal edema and inflammation of the mucosa (fig. 2, A). In other areas foreign body giant cells can be seen associated with fragments of suture material. The renal pelvis is covered partially by transitional epithelium. The wall is edematous, chronically inflamed with areas of focal squamous metaplasia and has bundles of smooth muscle (fig. 2, B). ANATOMICAL DIAGNOSES
Fistulous tract between intestinal wall and urinary tract tissue with chronic inflammation and scarring.
Renal pelvis with chronic inflammation and focal squamous metaplasia. POSTOPERATIVE COURSE
The patient did well after the operation with serum electrolytes and renal function returning to normal. A followup IVP revealed decreased size of the renal pelves bilaterally with improved excretion and visualization of both ureters. Dr. Charles N. Carney, Associate Professor, Department of Pathology, University of North Carolina at Chapel Hill provided assistance in preparation of the pathology material. REFERENCES
1. Milne, M. D.: Renal tubular dysfunction. In: Diseases of the Kidney, 2nd ed. Edited by M. B. Strauss and L. G. Welt. Boston: Little & Brown, Inc., p. 1071, 1971. 2. Abbassi, V., Lowe, C. U. and Calcagno, P. L.: Oculo-cerebrorenal syndrome: a review. Amer. J. Dis. Child., 115: 145, 1968. 3. Yong, J.M. and Sanderson, K.V.: Photosensitive dermatitis and renal tubular acidosis after ingestion of calcium cyclamate. Lancet, 2: 1273, 1969. 4. Woodbury, D. M.: Analgesics-antipyretics, anti-inflammatory agents and inhibitors of uric acid synthesis. In: The Pharmacological Basis of Therapeutics, 4th ed. Edited by L. S. Goodman and A. Gilman. New York: Macmillan Co., p. 317, 1970.
THE JOURNAL OF UROLOGY
Copyright © 1978 by The Williams & Wilkins Co.
Clinicopathologi cal Conference COMA AND HYPERCHLOREMIC ACIDOSIS JAMES MANDELL*
AND
FLOYD A. FRIEDt
From the Department of Surgery, Division of Urology, The University of North Carolina School of Medicine, Chapel Hill, North Carolina
PRESENTATION OF CASE:j:
Dr. James Mandell. A 43-year-old black woman was admitted to a local hospital in a comatose state. This condition had been preceded by a 2-day history of extreme lethargy, unresponsiveness and poor oral alimentation. The patient apparently had been without complaints, other than headaches, for 3 days before the onset of the stuporous state. There was no history of drug or alcohol ingestion, head or other trauma, seizures, hypertension, fever or renal disease. Pertinent physical findings on that hospitalization included blood pressure 150/90 mm. Hg, pulse 76, respiration 18 and temperature •100.4C. The patient was lethargic and uncommunicative but moved all extremities. The neck was supple. Chest, heart and abdominal examinations were normal. Neurologic examination revealed no other localizing signs. The hematocrit was 34 per cent, white blood count 5,000/mm. 3 with 70 per cent segmented neutrophils and urinalysis was normal except for a specific gravity of 1.009 and occasional rod-shaped bacteria. The serum sodium was 131 mEq./1., potassium 3.9 mEq./1., chloride 108 mEq./1. and phosphorus 5 mg. per cent. An SMA-12 survey was normal. The blood urea nitrogen was 82 mg. per cent, alkaline phosphatase 95 units and lactic dehydrogenase 204 units. Stool for occult blood was negative. Skull and chest x-rays were within normal limits. A lumbar puncture showed an opening pressure of 300 mm. water, with clear fluid that was microscopically negative. The patient was referred to our hospital. Physical findings when the patient was admitted to this institution remained unchanged except for the questionable appearance of blurred optic disks bilaterally. The medical history was unremarkable except for an operation 1¼ years earlier for internal drainage of a pancreatic pseudocyst. Admission laboratory data revealed serum sodium 151 mEq./1., potassium 3.5 mEq./1., chloride greater than 130 mEq./1., carbon dioxide 8 mEq./1., blood urea nitrogen 70 mg. per cent, creatinine 1.4 mg. per cent, glucose 100 mg. per cent, calcium 8.5 mg. per cent and phosphorus 3.1 mg. per cent. The serum bromide level was 7 mEq./1. and the salicylate level was 5 mg. per cent. Blood gases revealed an arterial oxygen pressure of 97 mm. Hg, carbon dioxide pressure 17 mm. Hg and a pH of 7.20. An initial electrocardiogram demonstrated 10 to 12 premature ventricular contractions but a repeat study the next day was normal. Urinalysis showed a pH of 6.0, greater than 50 red blood cells per high power field, 2 plus proteinuria and a specific gravity of 1.009. Upon the advice of a neurological consultant a right carotid arteriogram was performed on the night of admission to the hospital and was normal. Urine culture on the day of hospitalization yielded greater than 100,000 Escherichia coli and a blood culture was negative.
* Fellow in Pediatric Urology, University of North Carolina at Chapel Hill. t Professor of Surgery, Chief of Urology, University of North Carolina at Chapel Hill. :j: Case presented at Urological Grand Rounds University of North Carolina at Chapel Hill, on October 13, 1977. '
Hydration, alkalization and potassium supplementation returned the patient to an alert conscious state within 12 hours. Questioning of the patient at this time revealed that she had not been taking medication other than an occasional analgesic for headaches. She reported that she had been in good health until the abdominal operation 18 months earlier. Since that time she had noticed progressive weakness, weight loss, anorexia and diarrhea. After correction of the initial electrolyte and fluid imbalance the serum electrolytes remained normal with the exception that the woman required persistent bicarbonate supplementation to prevent return of acidosis. After the patient had been hospitalized 3 days the serum creatinine value stabilized at 1.3 mg. per cent, with a blood urea nitrogen of 50 mg. per cent. Further neurologic evaluation, including an electroencephalogram and repeat lumbar puncture, were non-revealing. The woman was treated with ampicillin for the E. coli urinary tract infection and urologic consultation was obtained. DIFFERENTIAL DIAGNOSIS
Dr. Floyd A. Fried. An extensive neurologic evaluation had been performed without revealing the etiology of the coma. There was no apparent central nervous system lesion or underlying septicemia. The fact that the sensorium cleared rapidly after correction of the metabolic acidosis suggests that the stuporous state was secondary to the fluid and electrolyte imbalances. The essentials of the problem are a patient with mild renal insufficiency and hyperchloremic acidosis. Causes for hyperchloremic acidosis can be divided into 5 major categories: 1) renal tubular diseases, 2) ingestion of exogenous agents, 3) lactic or diabetic acidosis, 4) chronic diarrheal states and 5) urinary enteric fistulas. With regard to primary renal tubular acido:;;is, the form of the disorder seen in adults predominates in women. There is significant loss of potassium in the urine to the point at which periodic paralysis may be seen. 1 The 24-hour excretion of potassium in this case was a modest 9 mEq./1. , which would make this diagnosis unlikely. Other renal tubular problems, such as oculocerebrorenal dystrophy (Lowe's syndrome), which is associated with congenital glaucoma, cataracts, mental retardation and rickets, 2 and consumption of large amounts of calcium cyclamate, which has been reported to produce a reversible form of renal tubular acidosis, 3 can be eliminated since neither of these entities applyies to our patient. Chronic ingestion of therapeutic doses of salicylates can produce a respiratory alkalosis through direct stimulation of the medullary respiratory center. This results in hyperventilation with a subsequent fall in carbon dioxide pressure. These changes ensue when plasma salicylate levels are in the range of 35 mg. per cent. Toxic doses of salicylates can produce a severe metabolic acidosis. 4 However, the salicylate level in this patient was 5 mg. per cent, effectively eliminating this as a possibility. Although the serum bromide was elevated moderately, levels less than 10 mEq./1. should not alter the
106
107 sensorium nor this of acidosis. questioning of patient is to have failed to any other exogenous agents that were ingested and could produce a state of acidosis. Various clinical entities that produce shock are associated with a lactic acidosis. This patient had no findings suggesting shock. An electrocardiogram and vital signs were normal. Although the hematocrit was 34 per cent there was no suggestion of acute blood loss. A blood culture revealed no growth. All of these data indicate that the acidosis was not secondary to shock. Diabetic acidosis also is eliminated from consideration with the findings of normal blood sugar levels. Chronic diarrheal states can result in depletion of sodium, potassium and bicarbonate with the development of a hyperchlorernia. The patient reported that she had long-standing diarrhea, which had developed since the operation 18 months earlier. Persistent diarrhea of this degree of severity with resultant acidosis brings to mind inflammatory bowel disease, neoplasia and villous adenoma. The only data we are afforded concerning the bowel is that the stool contained no blood. In view of the paucity of data I believe that it is likely that the chronic diarrhea certainly is aggravating the acidosis but it appears unlikely that it is the primary problem. Thus, the obvious causes for acidosis, renal tubular disease, exogenous agents, diabetes, shock and primary bowel disease seem to be unlikely. A review of the history revealed that 1½
earlier the had had a internally a of small The 1-1u,o;,,iu111uv that a fistula had been created inadvertently between urinary tract and small intestine is intriguing. A urinary enteric fistula could explain the development of chronic diarrhea with hyperchloremic acidosis. Of the renal problems that could be mistaken for pancreatic pseudocyst, a large renal cyst or distended renal pelvis com.es to mind. Since most renal cysts have no significant communication with the renal collecting system I would favor the diagnosis of a large hydronephrotic renal pelvis, perhaps secondary to congenital ureteropelvic junction obstruction with an iatrogenic fistula to the small bowel. The creation of such a fistula would result in increased fluid loss with loss of sodium, potassium and bicarbonate. The large amount of urea entering the bowel would further explain the elevated blooC: urea nitrogen with a near normal serum creatinine. DISCUSSANTS' DIAGNOSES
Stupor secondary to metabolic acidosis. Hyperchloremic acidosis secondary to chronic diarrhea state with possible urinary enteric fistula as underlying source. DISCUSSION OF FINDINGS AND SURGERY
Doctor Mandell. An excretory urogram (IVP) demonstrated bilateral pyelocaliectasis. Gradual opacification of the small
Fm. 1. A, IVP reveals bilateral pyelocaliectasis, worse on right side, with contrast medium seen in small intestine (arrow). B, left retrograde pyelogram reveals ureteropelvicjunction obstruction and communication between renal pelvis and small intestine (arrow).
Fm. 2. A, photomicrograph of intestinal epithelium demonstrates Brunner's glands with edema and inflammation of mucosa. B, photomicrograph of renal pelvis demonstrates diffuse edema and chronic inflammation.
CLINICOPATHOLOGICAL CONFERENCE
108
bowel was noted. A retrograde pyelogram of the left upper tract demonstrated a ureteropelvic junction obstruction and a left urinary enteric fistula (fig. 1). Left pyeloplasty and takedown of the fistulous tract were performed and, subsequently, a right pyeloplasty was performed without event. DISCUSSION OF PATHOLOGY
Dr. Charles N. Carney. The surgically resected specimen consisted of a segment of small intestine and attached renal pelvis. The intestinal tissue has mucosal glands lined by tall columnar intestinal epithelium with goblet cells and columnar epithelium like that of the Brunner's glands with flattened basal nuclei and granular acidophilic cytoplasm. There is focal edema and inflammation of the mucosa (fig. 2, A). In other areas foreign body giant cells can be seen associated with fragments of suture material. The renal pelvis is covered partially by transitional epithelium. The wall is edematous, chronically inflamed with areas of focal squamous metaplasia and has bundles of smooth muscle (fig. 2, B). ANATOMICAL DIAGNOSES
Fistulous tract between intestinal wall and urinary tract tissue with chronic inflammation and scarring.
Renal pelvis with chronic inflammation and focal squamous metaplasia. POSTOPERATIVE COURSE
The patient did well after the operation with serum electrolytes and renal function returning to normal. A followup IVP revealed decreased size of the renal pelves bilaterally with improved excretion and visualization of both ureters. Dr. Charles N. Carney, Associate Professor, Department of Pathology, University of North Carolina at Chapel Hill provided assistance in preparation of the pathology material. REFERENCES
1. Milne, M. D.: Renal tubular dysfunction. In: Diseases of the Kidney, 2nd ed. Edited by M. B. Strauss and L. G. Welt. Boston: Little & Brown, Inc., p. 1071, 1971. 2. Abbassi, V., Lowe, C. U. and Calcagno, P. L.: Oculo-cerebrorenal syndrome: a review. Amer. J. Dis. Child., 115: 145, 1968. 3. Yong, J.M. and Sanderson, K.V.: Photosensitive dermatitis and renal tubular acidosis after ingestion of calcium cyclamate. Lancet, 2: 1273, 1969. 4. Woodbury, D. M.: Analgesics-antipyretics, anti-inflammatory agents and inhibitors of uric acid synthesis. In: The Pharmacological Basis of Therapeutics, 4th ed. Edited by L. S. Goodman and A. Gilman. New York: Macmillan Co., p. 317, 1970.
