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192

SA

MEDIESE

TYD

KRIF

4 Augustu

1979

Asymptomatic Arsine
H. LEVY,

ephrotoxicit)
H. R. SCH EIDER, F. J. MIL TE

A Case Report
J. R. LEWI

D.T.

SUMMARY
A completely asymptomatic patient wi:h arsine nephrotoxicity is described. The light and electron microscopic appearances of the kidney biopsy specimen are documented. The pathogenesis of the lesions, the usual manifestations of arsine exposure, and how these differed from those seen in our patient, are discussed.

S. Afr. med. J.. 56. 192 (1979).

Arsine is one of the most toxic gases known to man and causes cough with pyrexia. haemolysis, jaundice. gastro-intestinal di turbances and haematuria or haemoglobinuria. The prognosis depends on the degree of kidney damage and is directly related to the recovery of renal function. Anuria is usually fatal. unle s exchange transfusion. haemodialysis or peritoneal dialysi is instituted. Mild presentations have been recorded in the literature. but all were of sufficient severity to attract medical attention. Blood transfu ions are given for anaemia and urine i alkalinized. Our patient was totally asymptomatic and would have escaped detection had arsine not been incriminated in the illnesses and deaths of others in his work environment.

CASE REPORT
The patient is a 37-year-old man who works as an analyst at a platinum metal refinery on the East Rand. On 28 February 197 he received small samples of an aluminium/ platinum group metal alloy which he crushed with a standard hammer and buckboard method. Further samples were handled in a similar manner on 7 March 1978. and. in the intervening period. the first set of samples sub equently joined by (he o(her samples was left in his office. These samples were later shown to be evolving arsine ga on standing in ambient air. Approximately 2 weeks before our patient presented. a worker in the refinery had died as a result of arsine poi oning. He had al 0 been handling the aluminium pla(inum group metal allav. After the death of the worker. personnel were informed of the possibility of arsine

OeparrmcnI of Mcdicine. nivcrsirv of the Witwatersrand and Johannesburg General Hospital. Johannesburg 11. LE\')'. R,.,' .. ~I.Jl. 13.( 11 .. IlIterll

11. H. SCII1'\EIDEH ..\I.B. (lI.B. F.e.p. (S ..~.I . .\/edical Registrar F. .I. \IlL:'-JE. F.CP. (s ..~.l. ~l.n .. Sellior Physiciall. Rellal Ullit
School of Palhology. Soulh African Instilule for Medical Research and ni\'ersity of IheWitwaiersrand, Johannesburg

.I.
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H. LE\\T\'. T. NL\'J'\'.

~l.U. U.CH .. ~I.R. n.CH ..

F.F.

PATH ..

Sellior Pathologist

Regivtmr

Dote received: 5 January 1979.

exposure and everyone in the refinery and laboratory was examined. On 12 March 197 , the patient presented for examination. ystematic questioning revealed that he was fit, having been passed as normal for an insurance examination in 1971 and by the Phthisis Board in September 1977. He had no burning on micturition, no urgency, and no frequency. There wa no hesitancy on passing urine and hiS stream wa good. There had been no period of oliguria or anuria. Careful questioning failed to reveal any previous ymptoms of urinary tract abnormality or any other cause of haematuria or proteinuria. He is a blood donor. and after having given 5 I units he wa.· told he had become Australia antigen-positive. He had not been ill and had never been jaundiced. He had had no gastrointestinal symptom during the preceding year. Examination on the same day revealed an alert. completely normal middle-aged man. His blood pressure was 110 80 mmHg. rine testing showed moderate haematuria. and mild proteinuria was revealed with dipsticks, although he had been completely well during the intervening period. Ophthalmoscopic examination was negative. There was no renal angle tenderness or renal artery bruit. A radiograph of the chest and an ECG were normal. On admission to the Chamber of Mines Hospital, the haemoglobin concentration was 14.2 g/dl. and there was no evidence of haemolysis. The ESR was 14 mm/h. The serum electrolyte level was normal, the serum urea level was 9,8 mmoJ/l, and the serum creatinine level was 132.6 fJ.mol/1. The results of a midstream urine examination and 24-h urine collections are shown in Tables I and JI respectively. The cercarial indirect fluorescent antibody test was negative. TO arsenic was found in the specimen of hair submitted for examination. An excretory urogram performed on 11 April 1978 was normal. with an excellent nephrogram phase. The kidneys excreted the contrast medium simultaneously. On admission to the Johannesburg General Hospital on 17 April 1978 the full blood count was normal. the ESR was 5 mm/h and the liver function tests were negative. The erum electrolyte level wa normal, the erum urea level wa elevated (8,5 mmol/I), and the serum creatinine level was normal (123,8 fJ.molll). The midstream urine examination and the 24-h urine collections showed a total protein of 0, I g/l. The Addis count was normal. no casts were een (Table 11). and Au tralia antigen wa ab ent. Serum immunoglobulin and complement level were normal, and nephritic factor was present in trace amounts. The renal biopsy specimen obtained on 20 April 1978 con isted of cortical tissue in which the main pathological change were een in the proximal tubules. The lining epithelial cells were swollen and many of the nuclei contained prominent nucleoli.

5 123. with the tubules in this area showing mild atrophy and thickening uf their ba emem membrane (Fig. and on the histological appear· ance of the kidney pecimen. ny ore Fig. No 9rowth No 9rowth Not done 24·HOUR URINE COLLECTIONS 5 Apnl 1978 1 710 8840 7. Fig. A large nucleolus is \'isible (electron microscopy x 8 700). The cell on the right shows nuclear degeneration with chromatin clumping and shrinkage of the nucleus. except for mild glomerular tamponade. 3). 2.8 132.mol/l) Serum urea (mmol/I) Serum creatinine (J1.8 104 73'1. with the basement membranes remaining intact and of normal thicknes (Fig.mol/l) Creatinine clearance (ml/min) Urea clearance Addis count 1220 320 9724 9. . . Swollen /Ubular epithelial cell showing rupture of cytoplasmic membrane and liberation of cytoplasmic organelles into lumen (arrow). A small focal area of interstitial fibrosi wa present. with liberation of ytoplasmi organelles into the tubular lumens (Fig.of normal 1 900 000 erythrocytes and leucocytes 29 March 1978 Volume (ml) Urine urea (mmol/I) Urine creatinine (jJ.6 62 56 10 of normal Not done A number of these cells showed rupture of the cytoplasmic membranes. There were len glomeruli which appeared normal. 1. +. Tubule lumen filled with necrotic ccll~ in which Ihe gho I outline of nuclei can be seen I ilver melhcn3minefH and E x lOO). A diagno i of arsine nephrotoxicity wa made on the ba is of the history and elimination of other eau e of haematuria and proteinuria. while in others scattered binucleated cells were observed which were suggestive of tubular regeneration (Fig. 4). some were dilated and lined by an extremely flattened epithelium showing pyknotic nuclei. Within some tubules the changes had progressed to frank necrosis of the lining cells. Of the viable tubules.6 85 Not done 19 Apnl 1978 1900 292 9724 8. The blood vessels were normal.8 132. Direct immunofluorescence tests were negative for immunoglobulins and for complement. DISCUSSIO Arsine (A H:. 2).4 August 197Y SA MI:DICAL JOURNAL 193 TABLE I. MIDSTREAM URINE EXAMINATION 23 March 1978 Leucocyte count (/ml) Erythrocyte count (/ml) pH Protein Glucose Blood Culture 2000 13000 6 12 Apnl 1978 1000 1000 20 Apnl 1978 1000 25000 6 5 May 1978 1000 10000 6 trace 6 trace trace Staphylococcus epidermis and diphtheroids <100oo/ml TABLE 11.hydrogen arsenide) is a colourles nonirritating ga with an odour resembling that of garlic. I).' It i found whenever na~cem hydrogen i~ produced ID the pre ence of compounds which contain arsenic.

Initially.. (1958): S. P.' ItS properties became known in 1815 when Gehlen. 68. Dark red urine is passed 4 . E. Binucleatcd epithelial cells suggestive of regeneration (arrows) and dilated tubules lined by a flatlened epithelium (silvcr methenamine/H and E x 40). secondary to the haemolytic anaemia or sludging of renal circulation. and is independent of haemolysis. There is usually a 2 . Comad. H. S. 4. 3. 32. 1171. and haemolysis. Chamber of Mines Hospital. (1976): Ala. peripheral neuropathy may occur. C. 101. 8. 65. which becomes focal. A. Interstitial fibrosis with tbe tubules showing mild atrophy and thickened basemcUl membranes (H and E x-lO). which can be total. P . Muehrcke. R. et al. et al. Fowler. with the subsequent release of hydrogen in the presence of water to permit the formation of arsine. 4. J. G. et tll. industr.194 SA MEDTESE TVDSKRIF 4 Augustus 1979 Fig. . Bradlow. 559. dizziness and dyspnoea. med.• Ennis. C.. and recommend that persons who are at risk in their occupations regularly have their urine examined for arsenic and have routine urine and blood tests for detection of renal damage. Mazey. and the condition would have remained undetected had a specimen of urine not been examined.. 1433. Transverse white striae of the finger nails (Mees' stripes) have been observed 2 .. Arsine exposure occurs despite precautions. 7. (1970): Brit. 3. Editorial (1974): Lancet. REFERE CES J. weakness. and Weissberg.'" Encephalopathy and. L.' ecrotic renal tubules containing haemoglobin casts are characteristically observed at autopsy. Fig. and died 9 days later:" The first cases in South Africa were reported in 1958 in workers shovelling zinc ash into boiling sulphuric acid.. occur. Uldall. Jaundice is seen 24 . C.'" Sequential renal biopsies were performed by Muehrcke and Pirani' who demonstrated extensive tubular damage followed by rapid regeneration of tubular cells. Med . In the proximal tubule. Jenkins. nausea and vomiting. Greig. E.·. J. M.' Massive haemolysis with minimal impairment of renal function was described by Jenkins eT al. malai e. a Munich chemist. J. (1965): Tbid.48 hours after exposure and a bronze tint of the skin has been described. Horsiey. J. 7 .' Marrow depression has also been described·'" The prognosis of any patient depends on the degree of kidney damage and is directly related to urine output. AIr. B. B. and is consistent with previously reported biopsy findings. 372. Severe tubular damage has been described in arsine poisoning in the absence of extensive haemoglobinuria. unless heroic measures such as complete exchange transfusion.24-hour delay before symptoms occur. later. McHugb. J. (1975): Brit. results. (1968): Ann. these cells have a modified and apparently functionally defective structure. E. Hard'on. haemodialysis or peritoneal dialysis are instituted. sniffed some and was ill within an hour..' It is one of the most toxic gases known to man and has been incorporated into lewisite. W . med. B. and Reed. 13. 191. Ind. et al. R . accompanied by gastrointestinal disturbance or abdominal pain.. 1. Wilkinson. The glomerular basement membrane is thickened and diffuse interstitial fibrosis. Kazanuis.' For prevention. E. R. 6. Oliguria or anuria may result from either a direct toxic effect of inhibition of renal tubular cell respiration or hypoxia. and recent attempts at using geothermal and fossil fuel energy sources high in arsenic content may increase the incidence of exposure. Khan. 1. When anuria develops death is inevitable. Med . 2. develops.. M. 3.' or massive precipitation of the arsenic-haemoglobin-haptoglo- bin complex in the tubular lumen. .'·.. P . with vomiting and fever. Med . J.. C. strict industrial surveillance for the presence of arsine is necessary.' The renal biopsy specimen in our patient was suggestive of an episode of tubular necrosis followed by tubular regeneration with tubular obstruction and glomerular tamponade. J. B. H. We believe that asymptomatic exposure to arsine may occur...."'·' Arsine combines with haemoglobin... G. The arsenichaemoglobin complex is filtered by the glomeruli. intern. 1. 53. the commonest method of arsine generation has been a reaction between arsenic and aluminium. Arsine enters the body through inhalation. S. A. (1974): ew Eng!. Alteration in renal function may persist owing to basement membrane thickening' and may continue for prolonged periods after recovery from arsineinduced renal failure. headache. haematuria and jaundice and who recovered spontaneously with only transient renal impairment. for referring the patient.3 weeks after exposure. Our patient is unique in that he was totally asymptomatic at all times.6 hours later. J. Enslin.'" During recent years. A.' Uldall eT al: described 2 patients who were mildly affected with cystitis. Se. 27. contaminated with arsenic will liberate arsine when treated with acid. and Pi rani. 5. We should like to thank Dr R. med. and profound nephron atrophy occurs. a war gas.