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Potassium Paresis Following Ureterosigmoidostomy
THE JOURNAL OF UROLOGY
Yol. 85, No. 4 April 1961 'Copyright © 1961 by The Williams & Wilkins Co.
Printed in U.S.A.
POTASSIUM PARESIS FOLLOWING URETEROSIGMOIDOSTOMY LEE R. SATALINE, *
AND
JOSEPH M. SIMONELLI
From the Department of Medicine, Hospital of St. Raphael, New Haven, Conn.
The potassium ion is essential for muscle and nerve function. Excitation and conduction of the impulse along the fiber is electrochemical in nature and is made possible by the difference in the electrical potentials of the inner or negative, and the outer or positive surfaces of the cell membrane.1· 2 The difference in the concentrations of intracellular and extracellular potassium appears to be the major factor in the potential difference and alterations in the potassium concentration, either within or outside of the fiber, result in impaired function. The effects of potassium on muscle function have been extensively studied by Grob and his group. 3 Hypokalemic paralysis occurring as a result of medical or surgical treatment has been described in several illnesses including treated diabetic acidosis, cathartic induced diarrhea and massive diuresis following the anuric phase of renal failure, or with the use of diuretics. 4 Although potassium deficiency had been previously noted following ureterosigmoidostomy, 5 Diefenbach and his associates 6 first reported hypopotassemia with flaccid quadriplegia as a sequela to this procedure. The rarity of this condition is borne out by the fact that only 7 cases have been described since 1951. 5 - 11 -YVhile weakness and lethargy have been Accepted for publication June 23, 1960. * Present address: Veterans Administration Hospital, Dayton, Ohio. 1 Ling, G. and Gerard, R. W.: The normal membrane potential of frog sartorius fibers. J. Cell. & Comp. Physiol., 34: 383-396, 413-438, 1949. 2 N astuk, W. L. and Hodgkin, A. L.: The electrical activity of single muscle fibers. J. Cell. & Comp. Physiol., 35: 39-73, 1950. 3 Groh, D., Liljestrand, A. and Johns, R. J.: Potassium movement in normal subjects: Effect on muscle function. Am. J. Med., 23: 340-355, 1957. 4 Fourman, P.: In: Clinical Effects of Electrolyte Disturbances, edited by E. J. Ross. Philadelphia: J. B. Lippincott Co., 1959, p. 97. 5 Foster, F. P., Drew, D. W. and Wiss, E. J.: Hyperchloremic acidosis and potassium deficiency following total cystectomy and bilateral ureterosigmoidostomy. Lahey Clin. Bull., 6: 231-238, 1950. 6 Diefenbach, W. C. L., Fisk, S. C. and Gilson, S. B.: Hypopotassemia following bilateral ureterosigmoidostomy. New Eng. J. Med., 244: 326-328, 1951. 559
noted in other cases, potassium levels were either not obtained or were normal. The case reported here is similar to the second case of Straffon and Coppridge11 in that our patient was also considered originally to have a neurological disorder and because the paralysis occurred 14 years after the transplantation. However, it is unique because the ureterointestinal anastomosis was unilateral, one kidney having been removed previously. CASE REPORT
A 53-year-old nun was admitted to The Hospital of St. Raphael on June 8, 1959 with a flaccid quadriplegia. She had been well until the clay of admission when she had noted extreme weakness first in her legs and later progressing to involve the trunk and arms. Shortly before admission to the hospital she became lethargic and incontinent. An accurate past history was not available at that time. Physical examination revealed a pale and dehydrated white woman in a stuporous condition. Her speech was garbled and respirations were diaphragmatic with a rate of 30 per minute. She moved only her head and upper thorax. The blood pressure was 120/76 mm. Hg.; the pulse 80 and regular; the temperature lOOF. The pupils were equal and reacted to light. The tongue and mucous membranes were dry and coated. The lung fields were clear and the heart sounds were of good quality. No murmurs were heard. The abdomen 7 Matern, D. I.: Hypokalemia accompanying hyperchloremic acidosis after ureterosigmoidostomy. New Eng. J. Med., 250: 941-944, 1954. 8 Skanse, B. and Widen, T.: Potassium deficiency syndrome following bilateral ureterosigmoidostomy. J. Urol., 73: 62-66, 1955. 9 Loughlin, J. F.: Quadriplegia, hypopotassemia and hyperchloremic acidosis after bilateral ureterosigmoidostomy. New Eng. J. Nied., 25~: 329-332, 1956. 10 Steinbeck, A. W. and Tyrer, J. H.: Hypokalemic paresis after bilateral ureterosigmoidostomy and treatment of a case. Brit. J. Urol., 31: 280-283, 1959. 11 Straffon, R. A. and Coppridge, A. J.: Respiratory paralysis and severe potassium depletion after ureterosigmoidostomy. J.A.M.A., 171: 139142, 1959.
560
SATALINE AND SIMONELLI
was slightly distended but soft. No tenderness or masses were noted. The bowel sounds were absent. Several old incisional scars were present. The rectal examination was negative except for a decrease in the sphincter tone. Neurological examination revealed hypoactive to absent tendon re.flexes in the extremities. No clonus or Babinski reflexes were present. The cranial nerves appeared to be intact. Passive movement of the limbs caused the patient to cry out as if in pain. Shortly after her admission the patient had a generalized convulsive episode which was controlled with sodium amytal. A lumbar puncture revealed normal pressure and spinal fluid. Therapy was supportive for the first 12 hours. The initial impression was acute polyneuritis or Landry's paralysis. The following day a review of her records revealed that the patient had undergone a hysterectomy in 1944 at which time a vesicovaginal fistula developed. Numerous attempts were made to close the fistula and during one of these procedures the left ureter was transected and a left ureterosigmoidostomy was performed. However the anastomosis broke down and the kidney became severely infected. In 1945 a left nephrectomy was performed. Between 1945 and 1947 many more attempts to close the fistula were made. It was during one of these procedures that the right ureter was injured and it was anastomosed to the sigmoid colon. Several days of anuria occurred postoperatively but renal function ultimately returned. The fistula was finally closed in 1948. She was next seen in 1953 when she was readmitted with severe pyelonephritis. An intravenous urogram demonstrated moderate hydronephrosis and a dilated ureter but without definite obstruction. She was again lost to followup until January 1958 when readmission was prompted by a second episode of severe pyelonephritis. An ileus was present and the patient appeared "apathetic and drowsy." These findings were thought to be sequelae of the severe infection. (Her serum potassium was 2.1 meq/L at this time and although electrolytic solutions were given to correct this deficit, it appears that its clinical significance was overlooked.) She was discharged asymptomatic. In March 1959 she was treated for a fractured rib. Severe osteoporosis was noted on the x-rays at this time. She was not seen again until her present admission. Laboratory studies on the morning following
admission revealed a hemoglobin of 10 gm. per cent with a 36 per cent hematocrit. The white blood cells, nonprotein nitrogen, fasting blood sugar, creatinine, calcium and phosphorus estimations were normal. The urinalysis was inaccurate due to fecal contamination. The serum sodium was 130 meq., the chloride 118 meq., the carbon dioxide 18 meq. and the potassium 2.3 meq. per liter. An electrocardiogram was normal. Serum protein electrophoresis revealed a small decrease in the albumin and a slight increase in the gamma globulin fraction. Intravenous and oral fluids containing large amounts of potassium were given. On the second hospital day the serum potassium had risen to 3 meq. per liter and muscle function and tendon reflexes returned. On the third day the potassium was 3.5 meq. per liter. At this time the patient noticed severe mid-back pain and a roentgenogram of the spine revealed pronounced osteoporosis and a compression fracture of vertebra T-6. A Taylor brace was prescribed by the orthopedic consultant. Therapy from this point on consisted of daily supplemental potassium as well as a high protein diet and norethandrolone (nilevar) was prescribed in an attempt to correct the osteoporosis. For the remainder of her hospital stay the serum potassium and sodium remained normal. Mild acidosis persisted as shown by elevated serum chloride levels (115-118 meq. per liter) and decreased carbon dioxide combining powers (16-18 meq. per liter). An intravenous urogram showed a slight decrease in the hydronephrosis. Renal function did not seem to be impaired since the dye promptly appeared in the kidney following injection. The patient has been followed regularly since discharge and 8 months later she was well and able to carry out her duties as a teacher. Mild hyperchloremic acidosis persists but no episodes of weakness have been noted. DISCUSSION
The mechanism of potassium loss following ureterosigmoid transplant has been ascribed to two mechanisms. The first is renal tubular dysfunction which results from repeated bouts of pyelonephritis caused by colon organisms ascending the ureter. Infection inevitably occurs following transplantation12 • 13 and Creevy and Reiser14 •2
Pool, T. L. and Cook, E. N.: Urographic
POTASSIUM PARESIS FOLLOvVING URETEROSIGMOIDOS'l'OMY
claimed that electrolyte disturbances were more common if there was pyelographic evidence of renal disease. The pathological changes in the tubular cell ·were considered secondary to infection and the tubular loss of potassium had been compared to that occurring in renal tubular acidosis.15 However, one obvious difference is noted: Whereas in the latter condition the kidneys are unable to acidify the urine, the urine obtained directly from the ureters of a patient with a ureterosigmoidostomy is ac:id. 16 , 17 The alkaline urine described in earlier reports was obtained from the colon and had undergone important electrolyte changes. Mitchell and Valk18 found that electrolyte disturbances would still occur in cases where renal tubular function as measured by CPAH and TmPAH was still within normal limits. Furthermore, it is known that electrolyte imbalance is absent or minimal in those subjects in whom rapid evacuation of the urine from the colon occurs. It would appear that renal tubular dysfunction is not the primary factor in producing potassium depletion. Indeed the pathological, and to some extent the electrolyte alterations described in patients with ureterosigrnoid anastomoses may actually be the result rather than the cause of the hypokalemia. The reasons for such conclusions will be discussed later. The second mechanism which has been proposed to explain the hypokalemia is based on the electrolyte disturbance,3 which occur when urine is diverted into the colon. Boyd in 1931'9 first described the hyperchloremic acidosis which follows ureterosigmoidostomy. Ferris and Odel 20 found that this complication occurred in 79 per cent of the 141 subjects they investigated but the vast majority were asymptomatic. Although both soclium and chloride ions are reabsorbed by the bowel mucosa, the causes of hyperchloremia are twofold: 1) The reabsorption of chloride is slightly study of the upper part of the urinary tract prior to and after cutaneous ureterostomy and ureterosigmoidostomy. J. Urol., 63: 228-231, 1950. 13 Graves, R. C. and Buddington, W. T.: Uretero-intestinal anastomosis. J. Urol., 63: 261-275, 1950. 14 Creevy, C. D. and Reiser, M. P.: 0 bservations upon the absorption of urinary constituents after ureterosigmoidostomy: The importance of renal damage. Surg., Gynec. & Obst., 95: 589-596, 1952. 15 Lapides, J.: Mechanism of electrolyte imbalance following ureterosigmoid transplantation. Surg., Gynec. & Obst., 93: 691-704, 1951. 16 Rosenberg, M. L.: Physiology of hyperchloremic acidosis following ureterosigmoid-
5Gl
greater than that of sodium. 17 , 21 The amount of C'hloride absorbed increases proportionately the nearer the anastomoses are to the cecum, the reason being the greater length of bowel mucosa traversed by the urine in its passage to the rectum.22 Polyvalent ions such as sulphates ancl phosphates which are normally present in the urine also increase chloride reabsorption. 23 2) The fluid compartment in which chloride is diluted following reabsorption is approximately seventenths that of sodium. 24 The sodium and chloride ions which are reabsorbed from the urine are replaced by the potassium and bicarbonate ions respectively and the colonic urine becomes alkaline.2 5 It is evident, therefore, that the serum potassium levels are lowered by the increased amounts of this ion which are secreted into the urine by the bowel. These electrolytic changes have been studicxl extensively by Stamey? 5 who believes that the potassium loss is a protective mechanism, whereby the severity of the acidosis is reduced. Because potassium and hydrogen ions compete for the same cellular enzyme systems 26 an increase in one ostomy: Study of urinary reabsorption with radioisotopes. J. Urol., 70: 569-580, 1953. 17 Parsons, F. M., Powell, F. G. N. and Pyrah, L. N.: Chemical imbalance following ureterocolic anastomosis. Lancet, 2: 599-602, 1952. 18 Mitchell, A. D. and Valk, W. L.: Hyperchloremic acidosis of ureterosigmoidostomies. J. Urol., 69: 82-95, 1953. 19 Boyd, J. D.: Chronic acidosis secondary to ureter al transplantation. Am. J. Dis. Child., 42: 366-371, 1931. 2°Ferris, D. 0. and Ode!, H. M.: Electrolyte pattern of blood after bilateral ureterosigmoidostomy. J.A.M.A., 142: 634-640, 1950. 21 Annis, D. and Alexander, M. K.: Differential absorption of electrolytes from the large bowel in relation to ureterosigmoid anastomosis. Lancet, 2: 603-606, 1952. 22 Kekwick, A., Paulley, J. W., Riches, E. W. and Semple, R.: Renal failure following ureterocolostomy. Brit. J. Urol., 23: 112-122, 1951. 23 Goldschmidt, S. and Dayton, A. B.: Studies in the mechanism of absorption from the intestine. V: The colon. The effect of sodium sulfate upon the absorption of sodium chloride when the salts are introduced simultaneously into the intestine. Am. J. Physiol., 48: 459-472, 1919. 24 Pyrah, L. N., Care, A. D., Reed, G. W. and Parsons, F. M.: The migration of sodium., chloride and potassium ions across the mucous membrane of the ileum. Brit. J. Surg., 42: 357-367, 1955. 25 Stamey, T. A.: The pathogenesis and implications of the electrolyte imbalance in ureterosigmoidostomy. Surg., Gynec. & Obst., 103: 736-758, 1956. 26 Berliner, R. W., Kennedy, T. J. Jr. and Orloff, J.: Relationship between acidification of the
562
SATALINE AND SIMONELLI
will therefore produce a decrease in the other. This can be proven by the use of carbonic anhydrase inhibitors which block hydrogen ion excretion thereby producing hyperkaluria, and by infusions of alkaline fluid which draw the hydrogen ion from the cells with its replacement by potassium. 26 In patients with ureterosigmoidostomies potassium depletion allows the hydrogen ion to shift from the vascular compartment to the intracellular space thus increasing the serum bicarbonate level in an attempt to combat the hyperchloremic acidosis. The effects of hypopotassemia on the kidney have only recently been emphasized and studied. Evidence has been presented that there is an increased susceptibility to kidney infection in rats that have been depleted of potassium. 27 The various clinical and pathological aspects of potassium nephropathy have been reviewed by Relman and Schwartz. 28 Vacuolar lesions of the tubules as seen in potassium depletion were found by Stamey25 in 30 per cent of the 57 autopsies performed on patients with ureterocolic anastomoses. In three or four of these cases the findings of pyelonephritis were minimal. While it is generally agreed that the renal lesions of hypokalemia are reversible in the earlier stages, at some time damage becomes irreversible. 28 The typical lesions of hypokalemic nephropathy may be masked by other kidney diseases which destroy renal tissue and thereby make accurate diagnoses impossible. It would be of paramount importance to know whether or not positive potassium balance in patients with ureterosigmoidostomies would limit or prevent recurrent episodes of pyelonephritis. The impaired renal concentrating power which occurs in hypopotassemia28 could explain the polyuria and resulting dehydration seen in many patients. Why severe potassium depletion should occur only in a few subjects may possibly be eA1Jlained by the variations in the sites of anastomoses, the length of time urine is retained in the colon and the amount of potassium in the diet. The occurrence of paralysis in potassium depletion is most apt to occur in subjects with acidosis29 but the urine and potassium metabolism. Am. J. Med., 11: 274-282, 1951. 27 Fourman, P., McCance, R. A. and Parker, R. A.: Chronic renal disease in rats following a temporary deficiency of potassium. Brit. J. Exp. Path., 37: 40-43, 1956. 28 Relman, A. S. and Schwartz, W. B.: The kidney in potassium depletion. Am. J. Med., 24: 764-773, 1958.
degree of hypokalemia necessary to produce paralysis varies from subject to subject. Depletion experiments conducted by Fourman and AinleyWalker30 on themselves produced marked weakness in both subjects but only one had a low serum potassium level. When the dehydration and acidosis were corrected the symptoms were minimal although the serum potassium was still below 3 meq./L in Fourman. It appears, therefore, that the lowered serum potassium is compensated by a decrease in the intracellular potassium thereby maintaining the electrical potential necessary for nerve and muscle function. The variability of electrocardiogram changes may be similarly explained. When paralysis occurs the administration of potassium will ameliorate the neurological manifestations long before the total deficit is corrected. It is believed this occurs as a result of the increased extracellular electrical potential which restores the proper potential difference between the inner and outer surfaces of the cell membrane. 3 Other late complications of ureterosigmoidostomy have been described. Osteomalacia following this operation was investigated by Harrison31 with calcium balance studies. Patients with acidosis were found to be in negative calcium balance. With the correction of the acidosis by alkali, positive calcium balance occurred. Maximum positive balance was attained only by the concurrent administration of vitamin D. The bone lesions in our patient appeared to be those of osteoporosis both roentgenographically and by laboratory studies. Silberman32 has reported a case of ammonia intoxication occurring in a patient with cirrhosis following ureterosigmoidostomy. Again the mechanism is uncertain but the ammonia formed when urea is split by the colon organisms may be absorbed as ammonium chloride. In the presence of impaired hepatic function, this excess ammonia may not be completely metabolized. Impaired carbohydrate metabolism characterized by elevated fasting blood sugar levels and a 29 Bland, J. H.: Disturbances of Body ;Fluids. 2nd ed. Philadelphia: W. B. Saunders Co.;p. 494. 3° Fourman, P.: Depletion of potassium induced in man with an exchange resin. Olin. Sc., 13: 93-110, 1954. 31 Harrison, A. R.: Clinical and metabolic observations on osteomalacia following ureterosigmoidostomy. Brit. J. Urol., 30: 455-461, 1958. 32 Silberman, R.: Ammonia intoxication following ureterosigmoidostomy in a patient with liver disease. Lancet, 2: 937-938, 1958.
POTASSIUM PARESIS FOLLOWING URETEROSIGMOIDOSTOMY
diabetic glucose tolerance curve was reported by Wilder and Cotton. 33 They postulated that the hyperchloremic acidosis interfered with normal glucose metabolism. The subJect was more recently studied by Wilson 34 but this author was unable to demonstrate any reduction in glucose tolerance. The treatment of electrolyte disturbances resulting from ureterosigmoidostomy is fraught with dangerous paradoxes. By administering large amounts of potassium the hydrogen ion is replaced in the cell thereby aggravating the acidosis. Bicarbonate therapy, on the other hand, will magnify the potassium deficit by increasing the renal excretion of this ion (the so-called hyperkaluria of alkalosis). It would seem logical, therefore, that therapy of any type should contain adequate amounts of both ions. Stamey25 recommends a potassium-sodium-citrate mix:ture and cautions the physician on the use of solutions containing no potassium which could produce death if the hypokalemia is severe enough. The recurrent bouts of pyelonephritis should be treated vigorously and for at least 14-21 days to minimize exacerbation. Although contaminated by the bacterial :flora of the colon, the urine should
l
33 Wilder, C. E. and Cotton, R. T.: Reabsorptive hyperchloremic acidosis following ureterosigmoidostomy. Report of a case showing disturbed carbohydrate metabolism. Am. J. Med., 15:
423-430, 1953.
34 Wilson, G.: The significance of impaired carbohydrate tolerance following ureterocolic .anastomosis. Brit. J. Urol., 30: 163-169, 1958.
1 !
563
be cultured and sensitivity obtained. In this way some degree of accuracy will be had in the selection of an antibiotic. SUMMARY
The case of a 53-year-old woman with hypokalemic paralysis secondary to ureterosigmoidostomy is described. The pathogenesis of the electrolyte changes is discussed. The concept of renal tubular dysfunction resulting from pyelonephritis appears to be inaccurate. The hyperchloremic acidosis apparently results from the selective colonic absorption of chloride in excess of sodium with the secretion of potassium into the urine retained within the bowel. Other complications of ureterosigmoidostomy are osteomalacia, impaired carbohydrate metabolism and ammonia intoxication. Therapy for the electrolyte disturbances should include adequate amounts of potassium as well as bicarbonate. We would like to thank Drs. Theodore Evans and Joseph Mignone of the Department of Medicine and Dr. William Perham of the orthopedic service for their assistance in preparing this paper. ADDENDUM
Since submitting this paper for publication, Angeloni and Scott have described a similar case of :flaccid quadriplegia in a patient who underwent unilateral ureterosigmoidostomy. (Lancet, 1: 1005-1006, 1960) .
Yol. 85, No. 4 April 1961 'Copyright © 1961 by The Williams & Wilkins Co.
Printed in U.S.A.
POTASSIUM PARESIS FOLLOWING URETEROSIGMOIDOSTOMY LEE R. SATALINE, *
AND
JOSEPH M. SIMONELLI
From the Department of Medicine, Hospital of St. Raphael, New Haven, Conn.
The potassium ion is essential for muscle and nerve function. Excitation and conduction of the impulse along the fiber is electrochemical in nature and is made possible by the difference in the electrical potentials of the inner or negative, and the outer or positive surfaces of the cell membrane.1· 2 The difference in the concentrations of intracellular and extracellular potassium appears to be the major factor in the potential difference and alterations in the potassium concentration, either within or outside of the fiber, result in impaired function. The effects of potassium on muscle function have been extensively studied by Grob and his group. 3 Hypokalemic paralysis occurring as a result of medical or surgical treatment has been described in several illnesses including treated diabetic acidosis, cathartic induced diarrhea and massive diuresis following the anuric phase of renal failure, or with the use of diuretics. 4 Although potassium deficiency had been previously noted following ureterosigmoidostomy, 5 Diefenbach and his associates 6 first reported hypopotassemia with flaccid quadriplegia as a sequela to this procedure. The rarity of this condition is borne out by the fact that only 7 cases have been described since 1951. 5 - 11 -YVhile weakness and lethargy have been Accepted for publication June 23, 1960. * Present address: Veterans Administration Hospital, Dayton, Ohio. 1 Ling, G. and Gerard, R. W.: The normal membrane potential of frog sartorius fibers. J. Cell. & Comp. Physiol., 34: 383-396, 413-438, 1949. 2 N astuk, W. L. and Hodgkin, A. L.: The electrical activity of single muscle fibers. J. Cell. & Comp. Physiol., 35: 39-73, 1950. 3 Groh, D., Liljestrand, A. and Johns, R. J.: Potassium movement in normal subjects: Effect on muscle function. Am. J. Med., 23: 340-355, 1957. 4 Fourman, P.: In: Clinical Effects of Electrolyte Disturbances, edited by E. J. Ross. Philadelphia: J. B. Lippincott Co., 1959, p. 97. 5 Foster, F. P., Drew, D. W. and Wiss, E. J.: Hyperchloremic acidosis and potassium deficiency following total cystectomy and bilateral ureterosigmoidostomy. Lahey Clin. Bull., 6: 231-238, 1950. 6 Diefenbach, W. C. L., Fisk, S. C. and Gilson, S. B.: Hypopotassemia following bilateral ureterosigmoidostomy. New Eng. J. Med., 244: 326-328, 1951. 559
noted in other cases, potassium levels were either not obtained or were normal. The case reported here is similar to the second case of Straffon and Coppridge11 in that our patient was also considered originally to have a neurological disorder and because the paralysis occurred 14 years after the transplantation. However, it is unique because the ureterointestinal anastomosis was unilateral, one kidney having been removed previously. CASE REPORT
A 53-year-old nun was admitted to The Hospital of St. Raphael on June 8, 1959 with a flaccid quadriplegia. She had been well until the clay of admission when she had noted extreme weakness first in her legs and later progressing to involve the trunk and arms. Shortly before admission to the hospital she became lethargic and incontinent. An accurate past history was not available at that time. Physical examination revealed a pale and dehydrated white woman in a stuporous condition. Her speech was garbled and respirations were diaphragmatic with a rate of 30 per minute. She moved only her head and upper thorax. The blood pressure was 120/76 mm. Hg.; the pulse 80 and regular; the temperature lOOF. The pupils were equal and reacted to light. The tongue and mucous membranes were dry and coated. The lung fields were clear and the heart sounds were of good quality. No murmurs were heard. The abdomen 7 Matern, D. I.: Hypokalemia accompanying hyperchloremic acidosis after ureterosigmoidostomy. New Eng. J. Med., 250: 941-944, 1954. 8 Skanse, B. and Widen, T.: Potassium deficiency syndrome following bilateral ureterosigmoidostomy. J. Urol., 73: 62-66, 1955. 9 Loughlin, J. F.: Quadriplegia, hypopotassemia and hyperchloremic acidosis after bilateral ureterosigmoidostomy. New Eng. J. Nied., 25~: 329-332, 1956. 10 Steinbeck, A. W. and Tyrer, J. H.: Hypokalemic paresis after bilateral ureterosigmoidostomy and treatment of a case. Brit. J. Urol., 31: 280-283, 1959. 11 Straffon, R. A. and Coppridge, A. J.: Respiratory paralysis and severe potassium depletion after ureterosigmoidostomy. J.A.M.A., 171: 139142, 1959.
560
SATALINE AND SIMONELLI
was slightly distended but soft. No tenderness or masses were noted. The bowel sounds were absent. Several old incisional scars were present. The rectal examination was negative except for a decrease in the sphincter tone. Neurological examination revealed hypoactive to absent tendon re.flexes in the extremities. No clonus or Babinski reflexes were present. The cranial nerves appeared to be intact. Passive movement of the limbs caused the patient to cry out as if in pain. Shortly after her admission the patient had a generalized convulsive episode which was controlled with sodium amytal. A lumbar puncture revealed normal pressure and spinal fluid. Therapy was supportive for the first 12 hours. The initial impression was acute polyneuritis or Landry's paralysis. The following day a review of her records revealed that the patient had undergone a hysterectomy in 1944 at which time a vesicovaginal fistula developed. Numerous attempts were made to close the fistula and during one of these procedures the left ureter was transected and a left ureterosigmoidostomy was performed. However the anastomosis broke down and the kidney became severely infected. In 1945 a left nephrectomy was performed. Between 1945 and 1947 many more attempts to close the fistula were made. It was during one of these procedures that the right ureter was injured and it was anastomosed to the sigmoid colon. Several days of anuria occurred postoperatively but renal function ultimately returned. The fistula was finally closed in 1948. She was next seen in 1953 when she was readmitted with severe pyelonephritis. An intravenous urogram demonstrated moderate hydronephrosis and a dilated ureter but without definite obstruction. She was again lost to followup until January 1958 when readmission was prompted by a second episode of severe pyelonephritis. An ileus was present and the patient appeared "apathetic and drowsy." These findings were thought to be sequelae of the severe infection. (Her serum potassium was 2.1 meq/L at this time and although electrolytic solutions were given to correct this deficit, it appears that its clinical significance was overlooked.) She was discharged asymptomatic. In March 1959 she was treated for a fractured rib. Severe osteoporosis was noted on the x-rays at this time. She was not seen again until her present admission. Laboratory studies on the morning following
admission revealed a hemoglobin of 10 gm. per cent with a 36 per cent hematocrit. The white blood cells, nonprotein nitrogen, fasting blood sugar, creatinine, calcium and phosphorus estimations were normal. The urinalysis was inaccurate due to fecal contamination. The serum sodium was 130 meq., the chloride 118 meq., the carbon dioxide 18 meq. and the potassium 2.3 meq. per liter. An electrocardiogram was normal. Serum protein electrophoresis revealed a small decrease in the albumin and a slight increase in the gamma globulin fraction. Intravenous and oral fluids containing large amounts of potassium were given. On the second hospital day the serum potassium had risen to 3 meq. per liter and muscle function and tendon reflexes returned. On the third day the potassium was 3.5 meq. per liter. At this time the patient noticed severe mid-back pain and a roentgenogram of the spine revealed pronounced osteoporosis and a compression fracture of vertebra T-6. A Taylor brace was prescribed by the orthopedic consultant. Therapy from this point on consisted of daily supplemental potassium as well as a high protein diet and norethandrolone (nilevar) was prescribed in an attempt to correct the osteoporosis. For the remainder of her hospital stay the serum potassium and sodium remained normal. Mild acidosis persisted as shown by elevated serum chloride levels (115-118 meq. per liter) and decreased carbon dioxide combining powers (16-18 meq. per liter). An intravenous urogram showed a slight decrease in the hydronephrosis. Renal function did not seem to be impaired since the dye promptly appeared in the kidney following injection. The patient has been followed regularly since discharge and 8 months later she was well and able to carry out her duties as a teacher. Mild hyperchloremic acidosis persists but no episodes of weakness have been noted. DISCUSSION
The mechanism of potassium loss following ureterosigmoid transplant has been ascribed to two mechanisms. The first is renal tubular dysfunction which results from repeated bouts of pyelonephritis caused by colon organisms ascending the ureter. Infection inevitably occurs following transplantation12 • 13 and Creevy and Reiser14 •2
Pool, T. L. and Cook, E. N.: Urographic
POTASSIUM PARESIS FOLLOvVING URETEROSIGMOIDOS'l'OMY
claimed that electrolyte disturbances were more common if there was pyelographic evidence of renal disease. The pathological changes in the tubular cell ·were considered secondary to infection and the tubular loss of potassium had been compared to that occurring in renal tubular acidosis.15 However, one obvious difference is noted: Whereas in the latter condition the kidneys are unable to acidify the urine, the urine obtained directly from the ureters of a patient with a ureterosigmoidostomy is ac:id. 16 , 17 The alkaline urine described in earlier reports was obtained from the colon and had undergone important electrolyte changes. Mitchell and Valk18 found that electrolyte disturbances would still occur in cases where renal tubular function as measured by CPAH and TmPAH was still within normal limits. Furthermore, it is known that electrolyte imbalance is absent or minimal in those subjects in whom rapid evacuation of the urine from the colon occurs. It would appear that renal tubular dysfunction is not the primary factor in producing potassium depletion. Indeed the pathological, and to some extent the electrolyte alterations described in patients with ureterosigrnoid anastomoses may actually be the result rather than the cause of the hypokalemia. The reasons for such conclusions will be discussed later. The second mechanism which has been proposed to explain the hypokalemia is based on the electrolyte disturbance,3 which occur when urine is diverted into the colon. Boyd in 1931'9 first described the hyperchloremic acidosis which follows ureterosigmoidostomy. Ferris and Odel 20 found that this complication occurred in 79 per cent of the 141 subjects they investigated but the vast majority were asymptomatic. Although both soclium and chloride ions are reabsorbed by the bowel mucosa, the causes of hyperchloremia are twofold: 1) The reabsorption of chloride is slightly study of the upper part of the urinary tract prior to and after cutaneous ureterostomy and ureterosigmoidostomy. J. Urol., 63: 228-231, 1950. 13 Graves, R. C. and Buddington, W. T.: Uretero-intestinal anastomosis. J. Urol., 63: 261-275, 1950. 14 Creevy, C. D. and Reiser, M. P.: 0 bservations upon the absorption of urinary constituents after ureterosigmoidostomy: The importance of renal damage. Surg., Gynec. & Obst., 95: 589-596, 1952. 15 Lapides, J.: Mechanism of electrolyte imbalance following ureterosigmoid transplantation. Surg., Gynec. & Obst., 93: 691-704, 1951. 16 Rosenberg, M. L.: Physiology of hyperchloremic acidosis following ureterosigmoid-
5Gl
greater than that of sodium. 17 , 21 The amount of C'hloride absorbed increases proportionately the nearer the anastomoses are to the cecum, the reason being the greater length of bowel mucosa traversed by the urine in its passage to the rectum.22 Polyvalent ions such as sulphates ancl phosphates which are normally present in the urine also increase chloride reabsorption. 23 2) The fluid compartment in which chloride is diluted following reabsorption is approximately seventenths that of sodium. 24 The sodium and chloride ions which are reabsorbed from the urine are replaced by the potassium and bicarbonate ions respectively and the colonic urine becomes alkaline.2 5 It is evident, therefore, that the serum potassium levels are lowered by the increased amounts of this ion which are secreted into the urine by the bowel. These electrolytic changes have been studicxl extensively by Stamey? 5 who believes that the potassium loss is a protective mechanism, whereby the severity of the acidosis is reduced. Because potassium and hydrogen ions compete for the same cellular enzyme systems 26 an increase in one ostomy: Study of urinary reabsorption with radioisotopes. J. Urol., 70: 569-580, 1953. 17 Parsons, F. M., Powell, F. G. N. and Pyrah, L. N.: Chemical imbalance following ureterocolic anastomosis. Lancet, 2: 599-602, 1952. 18 Mitchell, A. D. and Valk, W. L.: Hyperchloremic acidosis of ureterosigmoidostomies. J. Urol., 69: 82-95, 1953. 19 Boyd, J. D.: Chronic acidosis secondary to ureter al transplantation. Am. J. Dis. Child., 42: 366-371, 1931. 2°Ferris, D. 0. and Ode!, H. M.: Electrolyte pattern of blood after bilateral ureterosigmoidostomy. J.A.M.A., 142: 634-640, 1950. 21 Annis, D. and Alexander, M. K.: Differential absorption of electrolytes from the large bowel in relation to ureterosigmoid anastomosis. Lancet, 2: 603-606, 1952. 22 Kekwick, A., Paulley, J. W., Riches, E. W. and Semple, R.: Renal failure following ureterocolostomy. Brit. J. Urol., 23: 112-122, 1951. 23 Goldschmidt, S. and Dayton, A. B.: Studies in the mechanism of absorption from the intestine. V: The colon. The effect of sodium sulfate upon the absorption of sodium chloride when the salts are introduced simultaneously into the intestine. Am. J. Physiol., 48: 459-472, 1919. 24 Pyrah, L. N., Care, A. D., Reed, G. W. and Parsons, F. M.: The migration of sodium., chloride and potassium ions across the mucous membrane of the ileum. Brit. J. Surg., 42: 357-367, 1955. 25 Stamey, T. A.: The pathogenesis and implications of the electrolyte imbalance in ureterosigmoidostomy. Surg., Gynec. & Obst., 103: 736-758, 1956. 26 Berliner, R. W., Kennedy, T. J. Jr. and Orloff, J.: Relationship between acidification of the
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SATALINE AND SIMONELLI
will therefore produce a decrease in the other. This can be proven by the use of carbonic anhydrase inhibitors which block hydrogen ion excretion thereby producing hyperkaluria, and by infusions of alkaline fluid which draw the hydrogen ion from the cells with its replacement by potassium. 26 In patients with ureterosigmoidostomies potassium depletion allows the hydrogen ion to shift from the vascular compartment to the intracellular space thus increasing the serum bicarbonate level in an attempt to combat the hyperchloremic acidosis. The effects of hypopotassemia on the kidney have only recently been emphasized and studied. Evidence has been presented that there is an increased susceptibility to kidney infection in rats that have been depleted of potassium. 27 The various clinical and pathological aspects of potassium nephropathy have been reviewed by Relman and Schwartz. 28 Vacuolar lesions of the tubules as seen in potassium depletion were found by Stamey25 in 30 per cent of the 57 autopsies performed on patients with ureterocolic anastomoses. In three or four of these cases the findings of pyelonephritis were minimal. While it is generally agreed that the renal lesions of hypokalemia are reversible in the earlier stages, at some time damage becomes irreversible. 28 The typical lesions of hypokalemic nephropathy may be masked by other kidney diseases which destroy renal tissue and thereby make accurate diagnoses impossible. It would be of paramount importance to know whether or not positive potassium balance in patients with ureterosigmoidostomies would limit or prevent recurrent episodes of pyelonephritis. The impaired renal concentrating power which occurs in hypopotassemia28 could explain the polyuria and resulting dehydration seen in many patients. Why severe potassium depletion should occur only in a few subjects may possibly be eA1Jlained by the variations in the sites of anastomoses, the length of time urine is retained in the colon and the amount of potassium in the diet. The occurrence of paralysis in potassium depletion is most apt to occur in subjects with acidosis29 but the urine and potassium metabolism. Am. J. Med., 11: 274-282, 1951. 27 Fourman, P., McCance, R. A. and Parker, R. A.: Chronic renal disease in rats following a temporary deficiency of potassium. Brit. J. Exp. Path., 37: 40-43, 1956. 28 Relman, A. S. and Schwartz, W. B.: The kidney in potassium depletion. Am. J. Med., 24: 764-773, 1958.
degree of hypokalemia necessary to produce paralysis varies from subject to subject. Depletion experiments conducted by Fourman and AinleyWalker30 on themselves produced marked weakness in both subjects but only one had a low serum potassium level. When the dehydration and acidosis were corrected the symptoms were minimal although the serum potassium was still below 3 meq./L in Fourman. It appears, therefore, that the lowered serum potassium is compensated by a decrease in the intracellular potassium thereby maintaining the electrical potential necessary for nerve and muscle function. The variability of electrocardiogram changes may be similarly explained. When paralysis occurs the administration of potassium will ameliorate the neurological manifestations long before the total deficit is corrected. It is believed this occurs as a result of the increased extracellular electrical potential which restores the proper potential difference between the inner and outer surfaces of the cell membrane. 3 Other late complications of ureterosigmoidostomy have been described. Osteomalacia following this operation was investigated by Harrison31 with calcium balance studies. Patients with acidosis were found to be in negative calcium balance. With the correction of the acidosis by alkali, positive calcium balance occurred. Maximum positive balance was attained only by the concurrent administration of vitamin D. The bone lesions in our patient appeared to be those of osteoporosis both roentgenographically and by laboratory studies. Silberman32 has reported a case of ammonia intoxication occurring in a patient with cirrhosis following ureterosigmoidostomy. Again the mechanism is uncertain but the ammonia formed when urea is split by the colon organisms may be absorbed as ammonium chloride. In the presence of impaired hepatic function, this excess ammonia may not be completely metabolized. Impaired carbohydrate metabolism characterized by elevated fasting blood sugar levels and a 29 Bland, J. H.: Disturbances of Body ;Fluids. 2nd ed. Philadelphia: W. B. Saunders Co.;p. 494. 3° Fourman, P.: Depletion of potassium induced in man with an exchange resin. Olin. Sc., 13: 93-110, 1954. 31 Harrison, A. R.: Clinical and metabolic observations on osteomalacia following ureterosigmoidostomy. Brit. J. Urol., 30: 455-461, 1958. 32 Silberman, R.: Ammonia intoxication following ureterosigmoidostomy in a patient with liver disease. Lancet, 2: 937-938, 1958.
POTASSIUM PARESIS FOLLOWING URETEROSIGMOIDOSTOMY
diabetic glucose tolerance curve was reported by Wilder and Cotton. 33 They postulated that the hyperchloremic acidosis interfered with normal glucose metabolism. The subJect was more recently studied by Wilson 34 but this author was unable to demonstrate any reduction in glucose tolerance. The treatment of electrolyte disturbances resulting from ureterosigmoidostomy is fraught with dangerous paradoxes. By administering large amounts of potassium the hydrogen ion is replaced in the cell thereby aggravating the acidosis. Bicarbonate therapy, on the other hand, will magnify the potassium deficit by increasing the renal excretion of this ion (the so-called hyperkaluria of alkalosis). It would seem logical, therefore, that therapy of any type should contain adequate amounts of both ions. Stamey25 recommends a potassium-sodium-citrate mix:ture and cautions the physician on the use of solutions containing no potassium which could produce death if the hypokalemia is severe enough. The recurrent bouts of pyelonephritis should be treated vigorously and for at least 14-21 days to minimize exacerbation. Although contaminated by the bacterial :flora of the colon, the urine should
l
33 Wilder, C. E. and Cotton, R. T.: Reabsorptive hyperchloremic acidosis following ureterosigmoidostomy. Report of a case showing disturbed carbohydrate metabolism. Am. J. Med., 15:
423-430, 1953.
34 Wilson, G.: The significance of impaired carbohydrate tolerance following ureterocolic .anastomosis. Brit. J. Urol., 30: 163-169, 1958.
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be cultured and sensitivity obtained. In this way some degree of accuracy will be had in the selection of an antibiotic. SUMMARY
The case of a 53-year-old woman with hypokalemic paralysis secondary to ureterosigmoidostomy is described. The pathogenesis of the electrolyte changes is discussed. The concept of renal tubular dysfunction resulting from pyelonephritis appears to be inaccurate. The hyperchloremic acidosis apparently results from the selective colonic absorption of chloride in excess of sodium with the secretion of potassium into the urine retained within the bowel. Other complications of ureterosigmoidostomy are osteomalacia, impaired carbohydrate metabolism and ammonia intoxication. Therapy for the electrolyte disturbances should include adequate amounts of potassium as well as bicarbonate. We would like to thank Drs. Theodore Evans and Joseph Mignone of the Department of Medicine and Dr. William Perham of the orthopedic service for their assistance in preparing this paper. ADDENDUM
Since submitting this paper for publication, Angeloni and Scott have described a similar case of :flaccid quadriplegia in a patient who underwent unilateral ureterosigmoidostomy. (Lancet, 1: 1005-1006, 1960) .