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Development of Silica Calculi after Oral Administration of Magnesium Trisilicate
THE JOURNAL OF UROLOGY
Vol. 87, No. 6 ,Tune 1962 Copyright © 1962 by The Williams & Wilkins Co. Printed in U.S.A.
DEVELOPMENT OF SILICA CALCULI AFTER ORAL ADMIKISTRATION OF MAGNESIUM TRISILICATE CURT LAGERGREN From the Department of Diagnostic Radiology F, Karolinska sjukhuset, Karolinska Instit1itet, Stockholm, Sweden
Synthetic magnesium trisilicate is widely used in the treatment of hyperacidity in gastritis and gastric and duodenal ulcers. It was introduced in 1936 by Mutch,1- 3 who considered it to be superior to other antacids and absorbents by virtue of its strong neutralizing action. It has been stated that neither magnesium trisilicate nor the hydrated silica that is formed on the breakdown of the trisilicate in contact with hydrochloric acid is soluble, and therefore cannot be reabsorbed from the digestive tract. 2 • 4 In this respect these substances differ from, for instance, sodium bicarbonate, which can give rise to alkalosis through disturbance of the acid base equilibrium. The mechanism of breakdown and excretion of magnesium trisilicate has been studied by, among others, Page and associates. 5 When a silicate is acted on by an acid, part of the silica so formed is precipitated as a gel and part remains in solution as a colloid. It is probable that as a silicate passes through the digestive tract other breakdown products than silica are formed. In theory, these may include ortho-silicic acid (H,SiO,), which is soluble, meta-silicic acid (H2SiQ3) and tri-silicic acid (H.SisOs), which are partially soluble, and di-silicic acid (H2Si205), which is practically insoluble. Since the reaction between magnesium trisilicate and an acid is more complex than has previously been thought, Page and associates 5 considered it possible that part of the silica can be reabsorbed and excreted in the urine. They accordingly measured the excretion of Accepted for publication November 28, 1961. 1 Mutch, N.: Silicates of magnesium. Brit. M.
J., 1: 143-148, 1936. 2 Mutch, N.: Synthetic magnesium trisilicate. Its action in the alimentary tract. Brit. M. J., 1: 205-208, 1936. 3 Mutch, N.: Hydrated magnesium trisilicate in peptic ulceration. Brit. M. J., 1: 254-257, 1936. 4 Kraenier, M. and Aaron, B.: Use of hydrated trisilicate of magnesium for peptic ulcer. Am. J. Digest Dis., 7: 57-60, 1940. 5 Page, R. C., Heffner, R. R. and Frey, A.: Urinary excretion of silica in humans following oral administration of magnesium trisilicate. Am. J. Digest Dis., 8: 13-15, 1941.
994
silica in the urine of five healthy subjects before and after supply of magnesium trisilicate. It was found that the amount of silica excreted increased after intake, though not, it seemed, to a harmful extent. There appears to have been no mention in the literature of urinary calculus composed of silica until Hammarsten and associates 6 reported in 1953 a case of recurrent renal calculus, where chemical analysis of a stone showed it to be composed chiefly of silica. The patient had been taking tablets containing trisilicate regularly for several years for gastric ulcer. Hammarsten has since analyzed a further silica stone from a patient with a similar history. 7 Studying x-ray absorption in a plane ground rock crystal (Si02), she found that it closely resembles calcium oxalate and ammonium magnesium phosphate in this respect. The silica stones, however, had a fairly low radiopacity and this is ascribed to the calculus in the renal pelvis being in the gel state and to its being mixed with much fibrin. 6 One similar case with calculus caused by antacid therapy has later been reported. 8 In contradistinction to human being silica calculi are common in some animals and a serious problem among cattle in many areas. 9 • 10 The formation of calculus in connection with magnesium trisilicate therapy is presumably more common that would appear from the literature, and for this reason it has been considered of in6 Hammarsten, G., Helldorff, I., Magnusson, W. and Rilton, T.: Dubbelsidiga nj urstenar av
kiselsyra efter bruk av silikathaltigt antacidum. Svensk Lakartidning, 50: 1242-1246, 1953. 7 Hammarsten, G.: Terapi-inducerade urinvagskonkrement. Opuscula Medica, 3: 19-22, 1958. 8 Herman, J. R. and Goldberg, A. S.: New type of urinary calculus caused by antacid therapy. JAMA 174: 1206-1207, 1960. 9 Whiting, F., Conell, R. and Forman, S. A.: Silica urolithiasis in beef cattle. Can. J. Comp. Med. 22: 332-337, 1958. 1°Forman, S. A., Whiting, F. and Conell, R.: Silica urolithiasis in beef cattle. 3. Chemical and physical composition of the uroliths. Can. J. Comp. Med. 23: 157-162, 1959.
DEVELOPMENT OF SILICA CALCULI
99S
Fm. 1. Microradiograrn. of 100 microns thick section of silica stone. Central area is in structure and contains organic substance and silica. Alternating rings indicate silica and apatite. 15X.
terest to report 5 cases of silica stones where there had been regular medication with the trisilicate over a number of years. At the Department of Radiologic Diagnosis of this hospital x-ray crystallographic analysis is performed on urinary tract calculus from some 400 patients annually. During 1960 and 1961 there have been altogether 5 cases of silica stones. In three of them there were also small quantities of calcium hydroxyapatite, Ca10(PQ4)s(OH)2; in one, small quantities of calcium oxalate mono- and di-hydrate, while the fifth consisted only of silica. ]n all cases the silica was present in a fine crystalline form, and as a consequence the primary diffraction pattern in 3 cases consisted only of uninterpretable diffraction rings. The two other samples showed weak but readily identifiable powder diagrams. After the samples had been heated, clear diagrams that were characteristic of silica were obtained. In order to study the structure of the calculi, in 3 cases one half of the calculus was imbedded in methyl methac:rylatc and cut into thin slices. These were ground to 100 microns, and microradiographcd11 ln all cases the part of the stone consisting of silica gave similar pictures. As is seen from figure 1, where the central region of the 11 Lagergren, C.: Biophysical investigations of urinary calculi. x . ray crystallographic a.nd microradiogra.phic study. Acta. radio!. suppl., 133: pp. 1-71, 1956.
stone consists of silica, the structure is and mossy, with parts of low x-ray containing organic substance, alternating with areas of more radiopa.que silica. Within the surface layer there are concentric alternate rings oi silica and hyclroxyapatite with a still higher x-ray absorption. In the 3 cases where the underwent radiologic examination prior to the passage of the stone the ca.!culus was described a,, being of fairly low radiopacity, which property was clearly due to its structure. The structural picture and the finely crystalline form of the silica support Hammarsten's supposition that during the formation of the calculus the silica precipitated in the gel form. All ,5 patients had been taking tablets con taining magnesium trisilicate for gastric- ulcer and gastritis more or less regularly; in 2 cases daily, for 2-5 years. There was no evidence that any of them had exceeded the closes specified the respective manufacturers. Two of the had previously had attacks of the rena.l calculus type during trisilicatc therapy hut no stone been discovered. Since silica stones in the urinary tract do not occur unless trisilicate has been taken over a period as an antacid, the occurrence of these stones may be confidently ascribed to this substance. There is reason to doubt the wisdom of prolonged use of such preparations. In those. cases where they have been taken over a
996
CURT LAGERGREN
period an examination of the renal status should be made. SUMMARY
fJ.X-ray crystallographic analyses of calculi of the urinary tract from 800 patients disclosed 5 cases where the calculi consisted mainly of silica, which was present in a finely crystalline form. All 5 patients had been taking magnesium trisili-
cate in tablet form regularly over several years as an antacid for gastritis or ulcer. The dose had apparently not been remarkably large. Since oral administration of magnesium trisilicate evidently can give rise to the formation of silica stones, the renal status of patients on this therapy should be checked. As equally effective antacids are available they are to be preferred.
Vol. 87, No. 6 ,Tune 1962 Copyright © 1962 by The Williams & Wilkins Co. Printed in U.S.A.
DEVELOPMENT OF SILICA CALCULI AFTER ORAL ADMIKISTRATION OF MAGNESIUM TRISILICATE CURT LAGERGREN From the Department of Diagnostic Radiology F, Karolinska sjukhuset, Karolinska Instit1itet, Stockholm, Sweden
Synthetic magnesium trisilicate is widely used in the treatment of hyperacidity in gastritis and gastric and duodenal ulcers. It was introduced in 1936 by Mutch,1- 3 who considered it to be superior to other antacids and absorbents by virtue of its strong neutralizing action. It has been stated that neither magnesium trisilicate nor the hydrated silica that is formed on the breakdown of the trisilicate in contact with hydrochloric acid is soluble, and therefore cannot be reabsorbed from the digestive tract. 2 • 4 In this respect these substances differ from, for instance, sodium bicarbonate, which can give rise to alkalosis through disturbance of the acid base equilibrium. The mechanism of breakdown and excretion of magnesium trisilicate has been studied by, among others, Page and associates. 5 When a silicate is acted on by an acid, part of the silica so formed is precipitated as a gel and part remains in solution as a colloid. It is probable that as a silicate passes through the digestive tract other breakdown products than silica are formed. In theory, these may include ortho-silicic acid (H,SiO,), which is soluble, meta-silicic acid (H2SiQ3) and tri-silicic acid (H.SisOs), which are partially soluble, and di-silicic acid (H2Si205), which is practically insoluble. Since the reaction between magnesium trisilicate and an acid is more complex than has previously been thought, Page and associates 5 considered it possible that part of the silica can be reabsorbed and excreted in the urine. They accordingly measured the excretion of Accepted for publication November 28, 1961. 1 Mutch, N.: Silicates of magnesium. Brit. M.
J., 1: 143-148, 1936. 2 Mutch, N.: Synthetic magnesium trisilicate. Its action in the alimentary tract. Brit. M. J., 1: 205-208, 1936. 3 Mutch, N.: Hydrated magnesium trisilicate in peptic ulceration. Brit. M. J., 1: 254-257, 1936. 4 Kraenier, M. and Aaron, B.: Use of hydrated trisilicate of magnesium for peptic ulcer. Am. J. Digest Dis., 7: 57-60, 1940. 5 Page, R. C., Heffner, R. R. and Frey, A.: Urinary excretion of silica in humans following oral administration of magnesium trisilicate. Am. J. Digest Dis., 8: 13-15, 1941.
994
silica in the urine of five healthy subjects before and after supply of magnesium trisilicate. It was found that the amount of silica excreted increased after intake, though not, it seemed, to a harmful extent. There appears to have been no mention in the literature of urinary calculus composed of silica until Hammarsten and associates 6 reported in 1953 a case of recurrent renal calculus, where chemical analysis of a stone showed it to be composed chiefly of silica. The patient had been taking tablets containing trisilicate regularly for several years for gastric ulcer. Hammarsten has since analyzed a further silica stone from a patient with a similar history. 7 Studying x-ray absorption in a plane ground rock crystal (Si02), she found that it closely resembles calcium oxalate and ammonium magnesium phosphate in this respect. The silica stones, however, had a fairly low radiopacity and this is ascribed to the calculus in the renal pelvis being in the gel state and to its being mixed with much fibrin. 6 One similar case with calculus caused by antacid therapy has later been reported. 8 In contradistinction to human being silica calculi are common in some animals and a serious problem among cattle in many areas. 9 • 10 The formation of calculus in connection with magnesium trisilicate therapy is presumably more common that would appear from the literature, and for this reason it has been considered of in6 Hammarsten, G., Helldorff, I., Magnusson, W. and Rilton, T.: Dubbelsidiga nj urstenar av
kiselsyra efter bruk av silikathaltigt antacidum. Svensk Lakartidning, 50: 1242-1246, 1953. 7 Hammarsten, G.: Terapi-inducerade urinvagskonkrement. Opuscula Medica, 3: 19-22, 1958. 8 Herman, J. R. and Goldberg, A. S.: New type of urinary calculus caused by antacid therapy. JAMA 174: 1206-1207, 1960. 9 Whiting, F., Conell, R. and Forman, S. A.: Silica urolithiasis in beef cattle. Can. J. Comp. Med. 22: 332-337, 1958. 1°Forman, S. A., Whiting, F. and Conell, R.: Silica urolithiasis in beef cattle. 3. Chemical and physical composition of the uroliths. Can. J. Comp. Med. 23: 157-162, 1959.
DEVELOPMENT OF SILICA CALCULI
99S
Fm. 1. Microradiograrn. of 100 microns thick section of silica stone. Central area is in structure and contains organic substance and silica. Alternating rings indicate silica and apatite. 15X.
terest to report 5 cases of silica stones where there had been regular medication with the trisilicate over a number of years. At the Department of Radiologic Diagnosis of this hospital x-ray crystallographic analysis is performed on urinary tract calculus from some 400 patients annually. During 1960 and 1961 there have been altogether 5 cases of silica stones. In three of them there were also small quantities of calcium hydroxyapatite, Ca10(PQ4)s(OH)2; in one, small quantities of calcium oxalate mono- and di-hydrate, while the fifth consisted only of silica. ]n all cases the silica was present in a fine crystalline form, and as a consequence the primary diffraction pattern in 3 cases consisted only of uninterpretable diffraction rings. The two other samples showed weak but readily identifiable powder diagrams. After the samples had been heated, clear diagrams that were characteristic of silica were obtained. In order to study the structure of the calculi, in 3 cases one half of the calculus was imbedded in methyl methac:rylatc and cut into thin slices. These were ground to 100 microns, and microradiographcd11 ln all cases the part of the stone consisting of silica gave similar pictures. As is seen from figure 1, where the central region of the 11 Lagergren, C.: Biophysical investigations of urinary calculi. x . ray crystallographic a.nd microradiogra.phic study. Acta. radio!. suppl., 133: pp. 1-71, 1956.
stone consists of silica, the structure is and mossy, with parts of low x-ray containing organic substance, alternating with areas of more radiopa.que silica. Within the surface layer there are concentric alternate rings oi silica and hyclroxyapatite with a still higher x-ray absorption. In the 3 cases where the underwent radiologic examination prior to the passage of the stone the ca.!culus was described a,, being of fairly low radiopacity, which property was clearly due to its structure. The structural picture and the finely crystalline form of the silica support Hammarsten's supposition that during the formation of the calculus the silica precipitated in the gel form. All ,5 patients had been taking tablets con taining magnesium trisilicate for gastric- ulcer and gastritis more or less regularly; in 2 cases daily, for 2-5 years. There was no evidence that any of them had exceeded the closes specified the respective manufacturers. Two of the had previously had attacks of the rena.l calculus type during trisilicatc therapy hut no stone been discovered. Since silica stones in the urinary tract do not occur unless trisilicate has been taken over a period as an antacid, the occurrence of these stones may be confidently ascribed to this substance. There is reason to doubt the wisdom of prolonged use of such preparations. In those. cases where they have been taken over a
996
CURT LAGERGREN
period an examination of the renal status should be made. SUMMARY
fJ.X-ray crystallographic analyses of calculi of the urinary tract from 800 patients disclosed 5 cases where the calculi consisted mainly of silica, which was present in a finely crystalline form. All 5 patients had been taking magnesium trisili-
cate in tablet form regularly over several years as an antacid for gastritis or ulcer. The dose had apparently not been remarkably large. Since oral administration of magnesium trisilicate evidently can give rise to the formation of silica stones, the renal status of patients on this therapy should be checked. As equally effective antacids are available they are to be preferred.