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Revista do Hospital das Clínicas

On-line version ISSN 1678-9903

Rev. Hosp. Clin. vol.54 n.2 São Paulo Mar./Apr. 1999

http://dx.doi.org/10.1590/S0041-87811999000200003 

MEGABLADDER IN EXPERIMENTAL CHAGAS DISEASE: PATHOLOGICAL FEATURES OF THE BLADDER WALL

 

 

Luciano Henrique Gazoni Scremin, Carlos Eduardo Pereira Corbett, Márcia Dallastra Laurenti, Elizabeth Visone Nunes, Joaquim José Gama-Rodrigues and Masayuki Okumura

 

  RHCFAP/2960

SCREMIN, L.H.G. et al. - Megabladder in experimental Chagas disease. Pathological features of the bladder wall. Rev. Hosp. Clin. Fac. Med. S. Paulo, 54 (2): 43 - 46,1999.

 

SUMMARY: Mega-organs, primarily in the digestive tract, are well known to occur in chronic Chagas disease. Acute experimental infection with Trypanosoma cruzi results in parasitism of a wide range of cells, tissues, and organs, including the urinary bladder. Infection of BALB/c mice with 100,000 bloodstream forms of the Y strain of T. cruzi induced acute infection with intense parasitism of all layers of the urinary bladder. Parasites were found in the mucosa, lamina propria, muscular, adventitial connective, and fat tissue. Desquamate epithelial cells with amastigotes in the bladder lumen were also found. After 60 days of infection, mice inoculated with 50 bloodstream forms developed dilated, thin-walled bladders that had inflammatory infiltrates and foci of fibrosis replacing areas of damaged muscular layer. These lesions result from direct damage to the muscle fibers by the T. cruzi, leading to myosites, muscle damage, and scarring. Direct damage of paraganglia cells secondary to parasitism, leading to dilatation, damage of muscle fibers, and scarring with replacement of muscular tissue with connective tissue, should also be considered as a cause of functional disturbance of the urinary bladder.

 

DESCRIPTORS: Trypanosoma cruzi. Urinary bladder. Pathology.

 

 

The development of mega-organs in the digestive tract in victims of Chagas disease has been well documented in man and experimental models1,2. In an experimental murine model of Chagas disease, BALB/c mice infected with the Y strain of Trypanosome cruzi3 developed widespread parasitism of multiple organs. Parasites causing lesions in the mucosa, muscular layers and parasympathetic ganglions are believed to play a role in the etiopathogenesis of the lesions in the digestive tract4. Identification of a hydro-soluble T. cruzi antigen fraction in urine has been reported5,6. Parasitized epithelial cells were found in the lumen of urinary bladder3. The purpose of this study is to describe the pathologic features in the urinary bladder of the BALB/c mice after inoculation with T. cruzi, and to establish a relationship between this pathogenesis and the development of megabladder in experimental Chagas disease.

 

MATERIALS AND METHODS

Forty BALB/c mice (mean weight 20g) were inoculated intraperitoneally with 50 bloodstream forms of T. cruzi, Y strain. Five animals were sacrificed weekly during the first month, and from the 30th to the 90th day, five animals were sacrificed monthly; only two animals remained alive by the 90th day after inoculation.

To study the acute phase of the disease, another group of 10 BALB/c mice (mean weight 20g) were also inoculated with 100,000 bloodstream forms of T. cruzi, Y strain, and were sacrificed after one and two weeks of infection.

Fragments from different organs including the urinary bladder were obtained from all groups. The tissues were processed for histopathological studies, embedded in paraffin, and stained with H&E and Masson's stain.

 

RESULTS

In the acute phase, all animals had parasites in tissues from the heart, esophagus, stomach, and bowel, as well as the urinary bladder. Parasites could be detected in all phases of the experiment, in varying densities. After 2 months of infection, enlarged urinary bladders were observed.

In the acute phase, the bladders had parasites in all layers: the mucosa, own flide (Fig.1), muscular, adventitial connective, and fat tissue (Fig.2). Desquamate epithelial cells with amastigotes in the bladder lumen were found. The amastigotes proliferated within epithelial cells, muscle, mononuclear cell infiltrates, and interstitial cells scattered throughout the bladder wall.

 

Figure 1 - Parasites in the mucosa ( ­ ) and proper lamina ( ­ ). OM.200x

 

 

Figure 2 - Pseudocystis in muscular layers ( ­ ) and the adventitial tissue ( ­ ). OM. 400x

 

In three of the five animals killed after two months of infection, but in neither of the two remained animals after three months of infection, enlarged, dilated, and thin-walled bladders were observed. The bladders were enlarged to at least twice the normal size (Fig.3). Foci of mononuclear inflammatory cells in the muscular layer and in the connective tissue of the bladder wall were present. Bundles of collagen intermixed with muscle fibers were evident (Fig.4), as well as a reduced number of epithelial cell layers, indicating a distended transitional cell epithelium (Fig.5). Parasites were not seen in he megabladders.

 

Figure 3 - Megabladder: urinary bladder enlarged twice or more than normal size.

 

 

Figure 4 - Foci of connective tissue intermixed with muscle fibers ( ­ ). Om. 100x

 

 

Figure 5 - Distended transitional epithelium ( ­ ) and connective tissue intermixed with muscle fibers ( ­­ ). OM. 100x

 

 

DISCUSSION

Trypanosoma cruzi infection inducing mega-organ development in the digestive tract is well documented, as are enlarged bladders due to diseases such as diabetes mellitus7 and transections of pelvic enervation. However, the development of a megabladder due to Chagas disease has not been well characterized. There are only a few references in the literature concerning parasitism in the genito-urinary tract8. In experimental acute infection, widespread parasitism of many different organs, tissues, and cells has been documented3,9. Amastigotes proliferating in the urinary bladder wall are easily found in epithelial, interstitial, muscle, ganglia cells, macrophages, or other mesenchymal cells in the serosa. The parasitism in epithelial cells and in most types of cells of all layers of the bladder wall seen in the acute phase of T. cruzi infection may represent early pathological features of the urinary pathogenesis in Chagas disease. Later, after chronic infection, dilatation and thinning bladder walls lead to the diagnosis of chagasic megabladder. The pathological features of the chronic phase are mild inflammatory cell infiltrates together with collagen intermixed with muscle fibers, suggesting muscular repair after muscle cell damage. Whereas there is no report of megabladder in human Chagas disease cases, severely affected urinary bladders were described in man in a case of transplacental transmission to twins10.

Pseudocysts in smooth muscles of the urinary bladder were reported in dogs experimentally infected with T. cruzi11. Tropism to smooth muscle of the urinary bladder was also seen in mice experimentally infected with a wild strain isolated from D. marsupials12.

The megabladder in Chagas disease is characterized by collagen intermixed with muscle bundles, which probably results from direct damage by T. cruzi of muscle fibers, leading to myositis as is described for smooth muscle of the digestive tract3. Another mechanism of damage could be secondary to overdistention due destruction of the pelvic nervous system, similar to the flaccid neurogenic bladder8,13. Urologists and nephrologists should be aware that Chagas disease may be a possible cause of megabladder.

 

ACKNOWLEDGMENT: This work was supported by FAPESP, HC-FMUSP LIM-50 and CNPq. We are grateful to Márcio Carlos Baptista and Miguel da Silva Passos Jr. for photographic assistance; Cícero Geraldo dos Santos and Carmen do Socorro Guilherme for technical assistance, and Maria Daisi de Moraes and Lia Aparecida dos Santos Negrão for secretarial help.

 

RESUMO

RHCFAP/2960

SCREMIN, L.H.G. e col. - Mega bexiga na Doença de Chagas experimental. Caracteristicas patológicas da parede vesical. Rev. Hosp. Clín. Fac. Med. S. Paulo 54 (2): 43 - 46,1999.

 

Os "mega-órgãos" na Doença de Chagas são bem conhecidos, especialmente os desenvolvidos no sistema digestivo. A infecção aguda apresenta parasitismo de diversas células, tecidos e órgãos, dentre eles a bexiga urinária. Camundongos Balb/c infectados com 100.000 formas sanguíneas de cepa Y de T. cruzi mostraram intenso parasitismo de todas camadas da bexiga urinária na fase aguda. Os parasitas foram encontrados na mucosa, submucosa, lâmina própria, muscular, adventícia e tecido adiposo, além das células descamadas para a luz do órgão. Para produzir a fase crônica, os animais foram inoculados com a mesma cepa, porém apenas inóculo com 50 formas sangüíneas. Após sessenta dias de infecção, detectamos dilatações da parede vesical, assim como infiltrado inflamatório e focos de fibrose substituindo áreas musculares lesadas. Este achado pode ser resultado da ação direta do T. cruzi sobre as fibras musculares levando a miosite, destruição das fibras e consequente reparo. Lesão das células paraganglionares secundário ao parasitismo deve também ser considerado como causa de distúrbio urodinâmico evoluindo com dilatação, lesão das fibras musculares e substituição das mesmas por tecido conectivo.

 

DESCRITORES: T. cruzi. Bexiga urinária. Patologia.

 

REFERENCES

1. OKUMURA, M. & CORRÊA NETTO, A. - Produção experimental de "megas"em animais inoculados com Trypanosoma cruzi. Rev Hosp Clin Fac Med S Paulo 1961; 16 (5): 338-341.         [ Links ]

2. KÖBERLE, F. - Patogenese dos "megas". Rev Goiana de Med 1956; 2: 101-110.         [ Links ]

3. OKUMURA, M.; FRANÇA, L.C.M. & CORRÊA NETTO, A. - Comentários sobre a patogenia da Doença de Chagas: especial referência à infecção experimental em camundongos. Rev Hosp Clín Fac Med S Paulo 1963; 18: 151-164.         [ Links ]

4. OKUMURA, M. & CORRÊA NETTO, A. - Etiopatogenia do megacolon chagásico (Contribuição experimental). Rev Hosp Clín Fac Med S Paulo 1963; 18: 351-360.         [ Links ]

5. BONGERTZ, V. & HUNGERER, K.D. - Trypanosoma cruzi: circulating antigens. In: CONGRESS INTERNATIONAL OF CHAGAS DISEASE, Rio de Janeiro, 1979. Rio de Janeiro, s.n.t., 1979. p. 10-13.         [ Links ]

6. UMEZAWA, E.S. et al. - Trypanosoma cruzi: Detection of a circulating antigen in urine of chagasic patients sharing common epitopes with an immunodominant repetitive antigen. Exp Parasitol 1993; 76: 352-357.         [ Links ]

7. ROCHA, JN. - Disautonomia da bexiga urinária e seus tratamentos em pacientes diabéticos. Rev Bras Neurol 1991; 27(supl 1) 32S-36S.         [ Links ]

8. FIORANI, S.A.; FERREIRA, A.L.; CICONELLI, A.J. & MARTINS, A.C.- Lesions of neurons of the juxtaprostatic pelvic ganglions in acute experimental trypanosomiasis of mice. Rev Assoc Med Bras 1976; 22(2): 41-44.         [ Links ]

9. HANSON, W.L. & ROBERSON, E.L. - Density of parasites in various organs and the relation to the numbers of trypomastigotes in the blood during acute infection of the Trypanosoma cruzi in mice. J Protozool 1974; 21(4): 512-517.         [ Links ]

10. HOFF, R. et al. - Congenital Chagas disease in an urban population: investigation of infected twins. Trans R Soc Trop Med Hyg 1978; 72(3): 247-250.         [ Links ]

11. BARR, S.C. et al. - Pathologic features of dogs inoculated with North American Trypanosoma cruzi isolates. Am J Vet Res 1991; 52:2033-9.         [ Links ]

12. HERRERA, L. & URDANETA-MORALES, S. - Didelphis marsupialis: a primary reservoir of Trypanosoma cruzi in urban areas of Caracas, Venezuela. Ann Trop Med Parasitol 1992; 86:607-12.         [ Links ]

13. MAYO, ME. & HINMAN, F. - Structure and function of rabbit bladder altered by chronic obstruction or cystitis. Invest Urol 1976; 14(1): 6-9.         [ Links ]

 

 

Received for publication on the 05/11/98

 

Research developed in the Infectious Diseases Pathology Laboratory (LIM-50) of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo.

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