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Acute renal failure and methaemoglobinaemia due to copper sulphate poisoning KC Patel, BS Kulkarni, Vidya N AcharyaDepartment of Medicine, K. E. M. Hospital and Seth G. S. Medical College, Parel, Bombay-400 012., India
Correspondence Address: Source of Support: None, Conflict of Interest: None PMID: 1032833
Four cases of acute renal failure following copper sulphate poisoning have been described. All of them had intravascular haemolysis with varying degree of methaemoglobinaemia, -needing specific therapy for the same. They also were icteric due to acute hepatic damage and two of them died from irreversible hepatic damage despite dialysis which were given to them with a view to remove copper and uremic metabolites.
Copper sulphate poisoning is not un common in India, and until now many cases have been reported. [2],[4],[5],[7],[10],[11] Poisoning may be produced by various salts of copper which are commonly used in agriculture and in leather industry [10] as well as for medical purposes. [6] It is also reported after ingestion of beverages from contaminated pipes and vessels. [12] However, copper sulphate is the commonest salt used for suicidal purposes, especially among the lower income group in India [4] because of its easy availability at the counter. This salt is usually taken as a paste, powder or mixture [2] Exact dose in an individual case may be difficult to assess as neither the patient nor the relations are able to give proper information. Fatal dose is variable but on an average it is about 30 gms. No two cases show identical signs and symptoms as the emetic effect of the salt limits its toxicity. An excellent correlation between blood, RBC and plasma copper levels in acute copper sulphate poisoning with complication and prognosis is established very recently by Wahal et al [11] in 1976. They also stressed the relationship of prognosis to the time elapsing between ingestion of copper sulphate and institution of therapy. Though in an autopsy review of copper sulphate poisoning, renal changes of glomerular congestion and tubular necrosis have been described by Deodhar et al [4] there are no case reports of acute renal and hepatic failure, together with methaemoglobinaemia following copper sulphate poisoning treated during life. We are describing below 4 cases admitted to the K. E. M. Hospital for the management of copper sulphate poisoning associated with acute renal failure and methaemoglobinaemia.
Case No. 1: N.S. a 20 years old unmarried girl presumed to have taken about 3 gms. of copper sulphate on 11.4.1967 was admitted on 15.4.1967 with a history of emesis of 5 days' duration gradually increasing jaundice and oliguria of 4 days' duration. She had tonic as well as clonic convulsions preceeded by bifrontal headache of 2 days' duration. Past, personal, and family history was non-contributory. On examination, she was found to have puffiness of the face, icteric conjunctivae and normal temperature, blood pressure, pulse and respiration. Liver was one finger palpable and tender. Laboratory investigations revealed the following: Hb was 4.5 gms% ; Hematocrit was 19%, R.B.C. count 1.9 millions/cubic mm; Retic count 5%; W.B.C. 10400/cmm with differential count of P-69%, L-31%. BUN was 130 mg % , Creatinine 12.4 mg% and CO, content of 22.5 mMol/L. Urine showed a Sp. Gr. of 1015, pH of 6.7, Albumin +++, bile salts and pigments positive with numerous RBC casts. There was definite evidence of haemoglobinemia, hemoglobinuria and hemosiderinuria. Serum total bilirubin was 4.1 mg% with SGPT of 600 units. Serum Copper oxidase was 0.235 units. Total Serum Copper was 278 leg% with direct reacting copper of 52.32µg%. This patient was treated with Penicillamine 2 gms. daily together with 30 mgs. of Prednisolone without any diuretic response for 1 week. Hence she was given a hemodialysis and the corticoids were tapered off. Slowly with this her direct reacting copper came down to 2.01 µg% with a similar fall in the total serum copper level. She gradually started passing urine which showed frank blood in it. After recovery her radio-hippurate renogram showed normal function on the right side and no parenchymal rise on the left side. Repeat renogram after about 2 months showed only slight improvement of function on the left side. I.V.P. confirmed grossly impaired function on the left side. Aortogram done subsequently showed infarct in the left kidney. The patient slowly recovered and was in good health on 27.11.1967 when last, seen by us. Case No. 2: K.L. a 26 years old male was admitted to the K. E. M. Hospital on 15.3.1973 with a history of having taken about 25 gms of copper sulphate in half a glass of alcohol 4 days earlier. He had profuse vomitting on the following day and gradually lost consciousness, developed melena and went into anuria. On examination, the patient was found to be blue with warm extremities, icteric, acidotic, normotensive, drowsy with depressed deep reflexes and equivocal plantars response. He had ecchymotic patches on the left upper limb. Liver was palpable and tender. His investigations revealed Hb of 9 gms%, Hematocrit 27%; R.B.C. Count of 3.3 millions per cmm, W.B.C. 32,200/cmm with differential count of P-75% , L-19%, M-5% and E-1%. His BUN was 42 mg% and Creatinine 7 mg% CO 2 content was 19 mMol/L; Na-120 mEq/L, K-6 mEq/L Cl.-90 mEq/L. Patient's blood was chocolate coloured. His methaemoglobin level was 34%, Serum bilirubin was 22 mg% with direct reacting bilirubin 15 mg%, SGPT was greater than 200 units. E.C.G. showed sino-ventricular conduction. Patient was given hemodialysis and exchange transfusion of 1500 mls. of fresh blood together with Vitamin C 1000 mg. every 4 hourly and methylene blue 7 mls of 1% solution 3 doses, Patient did not respond to the treatment and died on 17.3.1975. Autopsy revealed fatty liver, congested oedematous lungs and kidneys together with petechial hemorrhage in the brain. Histopathology revealed focal hepatic necrosis with acute renal tubular necrosis See [Figure 1] and [Figure 2] on page 184A. Case No. 3: O.A., a 25 years old unmarried male took 25 gms. of copper sulphate and half a packet of tugone on 16.3.1974. He developed vomiting, epigastric pain, started passing high coloured urine, developed icterus and was admitted to the K. E. M. Hospital on the next day. Examination revealed a fully conscious icteric and normotensive person. His investigations were as follows: Hb 10.5 gms%; Hematocrit 31%; W.B.C. 9500/cmm with P-81%, L-18% and M-1%. Retic Count was 5.5% . His urine showed Sp. Gr. of 1008, pH of 8.5 Albumin ++++ together with free haemoglobin and few W.B.Cs. BUN was 50 mg% , serum creatinine was 6 mg% and serum electrolytes were normal. Serum total bilirubin was 6.2 mg% with direct 4.9 gm% together with SGPT of 40 units. Patient developed cyanosis with warm extremities 24 hours after admission when methaemoglobin level was found to be 30.3% His direct reacting serum copper level was 178.7 µg%. Patient was treated with Penicillamine together with Vitamin C and methylene blue. He was given a prolonged peritoneal dialysis. With this therapy, his serum copper fell serially to 85.02µ g% with other biochemical tests slowly returning to normality. Subsequently recovery was uneventful and patient was discharged on 25.3.1973. Case No. 4: A 21 years old male patient took 25gms of copper sulphate on 24.2.1975. He developed vomiting and abdominal pain. Next day he developed oliguria and hematuria for which he was admitted to K. E. M. Hospital on 26.2.1975. Examination revealed a fully conscious, normotensive dehydrated and icteric patient with ecchymosis. His investigations revealed a Hb of 6.4 gm%, Hematocrit 18%, BUN 98 mg%, Creatinine 9.9 mg%, CO 2 , content of 19.1 mMol/L. Na was 130 mEq/L, K-5.5 mEq/ L, C1.-97.5 mEq/L. Patient's plasma hemoglobin was 3.2%. His urine showed acidic pH and albumin ++++. Serum bilirubin was 10 mg%. Methaemoglobin was 38%. R.B.Cs. were very much fragile -fragility beginning with 0.65% of NaCl. Patient's blood used to get spontaneously hemolysed on collection. Hence serum copper estimations could not be done. Patient was put on peritoneal dialysis. His dialysate fluid coming out of peritoneal cavity was also positive for free haemoglobin. Patient did not respond to treatment and died on 1.3.1975. His autopsy revealed enlarged congested kidney with enlarged liver showing haemorrhages and areas of necrosis.
Genesis of acute renal failure is easily understood in the cases described. Intravascular haemolysis and direct nephrotoxic effect of copper can lead to tubular necrosis as seen in case No. 2 and 4. In intravascular haemolysis the renal failure results from tubular obstruction by cell debris and haemoglobin with back diffusion of filtrate through the damaged tubular walls. In case No. 1, renal infarct was an additional factor responsible for renal shut down. Case No. 3 appears to have developed reversible hepatic and renal tubular necrosis. That is why this patient recovered from anuria. Appearance of methaemoglobinaemia due to copper sulphate poisoning in sheep was recorded by Todd and Thompson [8] in 1961 and subsequently many reports have appeared in literature denoting this pathology. Copper salts are usually good oxidizing agents and when absorbed in general circulation it is likely that a fair amount of normal oxyhaemoglobin will be oxidized to ferric state viz, hemiglobin. In this ferric state hemoglobin loses its oxygen binding capacity. This clinical appearance of cyanosis will depend upon the amount of methemoglobin formed. Out of 4 cases two had developed clinical cyanosis and biochemical estimation of methaemoglobin showed that about one third of the total haemoglobin was converted to methaemoglobin. In the other two patients methaemoglobin levels were comparatively low with no clinical cyanosis. Normal serum copper level as reported by various authors in Western world ranges between 75-106 ug%. [1],[9] Some authors have reported high normal values. However, Indian normal level tallies with the former values viz. 75-106 µg%. Two of our patients where we have estimated -copper level showed values well above normal, and the percentage of methaemoglobin was also high indicating that a fair amount of copper is absorbed into the general circulation and this has oxidized hemoglobin to hemiglobin i.e. ferric state. The transfer of the electrons of NADH, NADPH and GSH systems usually restores the hemiglobin to hemoglobin state. Copper is supposed to affect these enzyme systems resulting into the decrease of glutathione and G-6-PD. At the time of admission, it was not possible to document whether our patients had a pre-existing G-6-PD1 enzyme deficiency or it was secondarily induced by high copper levels in the blood, Nevertheless it has been proved to be the result of excessive oxidant stress produced by copper in the production of methaemoglobin. [3] Two of our patients who survived were not found to have any G-6-PD deficiency on follow up. All our patients were treated with large amount of Vitamin 'C' and methylene blue to combat methaemoglobinemia which resulted in reduction of cyanosis. Two of our patients (Case No. 1 and 3) were given penicillamine and recovered. Both these cases were clinically much less moribund as compared to other two (case 2 and 4) who did not receive penicillamine and died of irreversible hepatic damage. Peritoneal and hemodialysis were used in our patients to reduce methaemoglobin levels and remove the copper and other uremic metabolites. However, we were able to salvage only 2 patients. The other two who succumbed despite dialysis had very high serum bilirubin levels indicating a severe damage to liver and erythropoietic system. Peritoneal dialysis, we feel, is a better method to remove the high levels of copper, since it is protein bound and since large amount of protein is lost in the dialysate during the dialysis procedure. This, in turn, will reduce the damaging effect of copper and hasten clinical recovery.
We would like to express our grateful thanks to Dr: Dorab K. Dastoor of Neuropathology Laboratory of J. J. Group of Hospital, for having done the copper levels for us. Our sincere thanks are due to the Dean, K. E. M. Hospital for granting us permission to use the hospital records to publish the cases.
[Figure 1], [Figure 2]
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