ORJGINAL ARTICLES

* The Pathogenesis ef Bilharzia] Hydroureter

S. B. Bhagwandeen, M.D., Senior Lecturer, Dept. of Pathology, University of Natal.**

Surgeons and Urologists working in endemic areas of bilharziasis have long recognized bilharzia! ureteric disease with its sequelae of hydroureter and hydroneph­rosis. What is not fully appreciated, however is the PATHOGENESIS of these ureteric changes.

It is generally believed that bilharzia! hydroureter is a late complication of a stenotic lesion (Ibrahim 1923: Girges, 1934; Ragheb, 1939; Campbell-Begg, 1944; Sayegh, 1950; Honey & Gelfand, 1960; and · Gregory, 1964). Thus the "golf-hole" ureteric orifice recognised by Fairley (1919) and Dew (1923), and the descriptions of Ibrahim (1923), Girges (1934) and Campbell-Begg (1944) all indicate late lesions. Vermooten (1937) believed that the ureteric lesions only became manifest about 8-10 years after the initial exposure.

Some authors have also admitted causes other than late stenotic lesions for the hydronephrosis. Vermooten, from both clinical experience and experimental evidence, postulated that if a segment of ureter was the seat of bilharzia! infection that segment would undergo dilation, either due to distal partial obstruction or to vesico­ureteral reflux. Marcks (1956) suggested a similar mechanism when he defined "ureterectasia".

Several authors also concede that in a small minority of cases vesicoureteral reflux may be the prime factor in producing hydroureter (Makar, 1948; Kirkaldy­Willis, 1948; Honey & Gelfand, 1960 and Gregory, 1964).

Despite the early observations of Fairley (1920) and Dew (1923), ureteric obstructive lesions in early acute bilharziasis have been recognised by few observers (Makar, 1948 and Kisner, 1952).

PRESENT STUDY

This investigation into the pathogenesis of bilharzia! hydroureter was undertaken at the University of Natal and is based on a CLINICAL study of 108 unselected patients presenting with active urinary bilharziasis. Each patient had a complete clinical examination, I.V.P., cystoscopic examination and ureteric catheterisation. Fellow-up I.V.P., and cystoscopy was done on 25 cases. The clinical findings were correlated with autop3y observations. For the AUTOPSY study 30 consecutive

*This article was read at the Medical Congress at Kitwe (1968)

** Present Address:- Head, Dept. of Pathology, University of Zambia.

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cases with macroscopic evidence of vesical bilharziasis. were selected. Microscopic and macroscopic examination was done of the bladder, ureters and kidneys.

From this study it became evident that several pathological progresses gave rise to a common manifes­tation of hydroureter and subsequent hydronephorsis. The causes may be summarised as follows:-

1. OBSTRUCTIVE: i. Acute phase-proliferative granul omata

occluding lumen. ii. Chronic phase-stricture of the ureter.

iii. Secondary ureteric calculi.

2. FUNCTIONAL: i. Uretero-Vesical reflux.

ii. Paralytic megaloureter.

1. OBSTRUCTIVE LESIONS: i. Acute Granulomata.

It is generally recognised that severe acute lesions in the bladder produce polypoid, granulomatous lesions. However, surprisingly few workers have recognised that similar lesions are frequently found in the lower third of the ureter.

Such an acute granuloma (Fig. 1) accompanied by the attendant odema and congestion of an acute inflamma­tion in the narrow confines of the ureter or at the orifice (Fig. 2) will result in partial if not complete, obstruction.

The diagnostic features of such an acute lesion have ~ been described elsewhere (Bhagwandeen, 1967). ~

ii. Stricture of the Ureter.

Bilharzia! stricture of the ureter is unfortunately generally believed to be the cause of hydroureter. It is by no means as common as believed. However it is easy to understand the progression of this lesion. Acute bilharzia! panureteritis (Fig. 3) results in muscle destruc­tion and subsequent healing by dense fibrous scar tissue. The scar tissue subsequently contracts producing a stricture (Fig. 4).

The commonest site of the stricture in this study was found to be in the vesical portion of the ureter (in its passage through the bladder wall). This produces the typical I.V.P. appearences-the "cobra-head" deformity in the early stage (Fig. 5) and the very gross picture in the long standing case (Fig. 6). Stricture of the upper end of the ureter is extremely rare (Simpson, 1963).

MEDICAL JOURNAL OF ZAMBIA July, 1969

iii. Ureteric Calculi.

Makar (1948) demonstrated that sheets of calcified ova may form a nidus forcalculus formation. In the present study no case of urinary calculosis was found. It is my view that a diathesis for calculi formation pre-exists and that calculi formation is subsequently promoted by the obstruction, stagnation and infection-the sequelae of chronic ureteric bilharziasis (Fig. 7).

2. FUNCTIONAL CAUSES: i. Uretero-V esical Incompetence.

Hutch et al. (1961), Zinner (1963), and Mathiesen (1964), have recently demonstrated the anatomical relationship and the physiological function of the U-V junction. All have emphasised the importance of the "sphincteric" function and its dependence on proper anatomical relationships.

Mathisen, moreover, demonstrated that chronic in-flammatory fibrosis, surgical trauma to the ureteric orifice,

I loss of elasticity of the intravesical ureter or a neurogenic

, bladder would irreversibly damage the U-V sphincter - _and precipitate reflux.

In vesical bilharziasis, as I have already shown there is considerable destruction of the normal structures. It has also been shown that bilharzia! involvement of the bladder is especially common around the trigone. Consequently chronic fibrosis and extensive calcification (Fig . 8) must surely deform normal anatomical relations and thus upset the normal physiologic functions.

Histopathology in the present study has revealed gross disturbance consequent on fibrosis and calcification of the lower end of the ureter and the bladder, especially in the U-V area (Fig. 9). Consequently permanent damage to the U-V sphincter is implicit and in the absence of an obstructive lesion proximally, will result in reflux.

If there is no extravesical ureteric muscular atony (due to segmental bilharzial involvement), the resultant back pressure manifests itself as a dilatation and tortuo­sity at the pelvi-ureteric junction (Fig. 10); but if there is co-existent segmental ureteritis, the back pressure will . produce segmental hydroureter (Fig. 11).

I ii. Paralytic Megaloureter.

Beach (1931) and Bobbit (1937) believed that neuromuscular disturbances of the ureter could lead to atony with secondary hydroureter and hydronephrosis . Benjamin (1956) demonstrated that an ob3tructive lesion also eventually resulted in an atonic ureter.

More recent work by Mathiesen (1964) reveals that the peristaltic wave in the ureter can move in both directions and the direction is dependent on the pressure gradient. The conduction of the peristaltic wave has been shown to be a myogenic impulse conducted locally and independent of the nervous system.

It is apparent then that a segmental destruction of the ureteric musculature will result in a failure of transmis­sion of the myogenic impulse. Such focal muscular destruction and atrophy (Fig. 12) is, as has been shown (Bhagwandeen, 1967), a common manifestation of

MEDICAL JOURNAL OF ZAMBIA July , 1969

ureteric bilharziasis. In such a ureter the bolus of urine transmitted by the peristaltic wave will be arrested aTllfe site of muscular destruction. There is as a result, local stagnation and an increase in the pressure gradient. Furthermore, a minimal obstructive element (not uncommon in the intra-vesical portion) and/or U-V reflux will compound the raised pressure gradient in the ureter. This increase in pressure gradient at the localised point,togetherwiththe loss of muralelasticitywillproduce a situation not unlike that pertaining in an arterial anaurysm. This will explain the common 1.V.P. finding of segmental hydroureter in the absence of any stenotic lesion. Such areas are found, on microscopy, to be the sites of chronic bilharziasis (Fig. 13).

Not infrequently the entire ·· length of the ureter is transformed by mural calcification into a rigid tube (Fig. 14). It is apparent that such a ureter will be incapable of initiating or propagating a peristaltic wave. This would mean in fact that the column of urine from the renal pelvis to the ureteric orifice would have a much higher pressure gradient than if it were interrupted by peristaltic waves acting as valves . The condition is aggravated by any degree of U-V reflux. Consequently we have an analogous situation to that of incompetent valves of the Saphenous system of veins of the lower limb. And these, as we know, would in similar situations rapidly progress to varicosities. In fact the tortuous varicose veins have their counterpart in the dilated tortuous ureters coverted by chronic bilharziasis into rigid tubes-but without appreciable obstruction. (Fig. 15). This finding bas been confirmed by autopsy studies.

DISCUSSION:

The above findings are significant and not merely an exercise in orderly classification. They have practical implications in the surgical management of these patients.

Where the obstruction is due to stenosis, resection and reimplantation of the affected ureter is justified.

However, it is obvious that such intervention is hardly indicated where the obstruction is due to an acute granulomatous bilharzia! lesion.

Functional causes of bilharzia! hydroureter are even more challenging. Surgical intervention implies recons­truction of an efficient U-V sphincter from permanently diseased tissue. It is obvious from the histopathology as demonstrated here that attempted reconstruction from grossly damaged and deceased tissue would be highly suspect.

The Surgeon and Urologist must therefore be highly critical in the evaluation of the cause of the hydroureter in each case.

Finally, various authors (Elsdon-Dew, 1962; Powell, 1967) have commented on or implied the benig­nity of urinary bilharziasis and on its self-limiting course. Surgeons and Urologists who see the complica­tions and Pathologists critically evaluating the histo­pathology will appreciate that it is wishful thinking to expect grossly scarred and deformed ureters to return to normal function unaided.

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MEDICAL JOURNAL OF ZAMBIA July, 1969 51

SUMMARY:

It is generally believed that bilharzia! hydroureter is a late manifestation of chronic fibrotic stricture. Clinical observations correlated with autopsy studies have demonstrated varied patho-physiological factors with a common presentation of hydroureter.

The significance of these causes are discussed and the importance of their recognition to the management of an individual case stressed.

Finally the myth of " benign bilharziasis" is exposed.

REFERENCES

Beach, W. (1931) J. Urol. 25: 367. Benjamin, J.A., Betheil, J.J., Emmel, V.M., Ramsay,

G.H. & Watson, J.S. (1956) J. Urol., 75 : 25. Bhagwandeen, S.B. (1967) S. Afr. m.j., 41: 950. Bobbit, R .M. (1937): J. Urol., 38; 562. Campbell-Begg, R. (1944): S. Afr. m.j., 18: 239. Dew, H .R. (1923); J. Path. Bact., 26: 27. Elsdon-Dew, R. (1962): in "Bilharziasis"-Ciba Founda­

tion Symposium. Ed. Wolstenholme, G .E.W. & O'Connor, M. (J. & A. Churchill, Ltd.) London. p.207.

Fairley, N .H. (1919): Quart. J. Med., 12: 391. (1920): J. Path. Bact., 23: 289.

Girges, R. (1934) : op. cit. Gelfand, M. (1950): "Schisto­somiasis in South Central Africa": Juta & Co., Ltd., Cape Town.

Gregory, l.L. (1964) : C. Afr. J. Med ., 10: 119. Honey, R .M. &. Gelfand, M (1960): C. Afr. J. Med., 6:

1,58, 109, 153, 199, & 248 .

Legend for illustrations on Pages 56, 59, 82

Fig. 1. Acute bilharzia! granuloma of the lower third of the ureter. All layers of the ureter are involved and the proliferative nature of the lesion is evident. The overgrowth into the lumen of the ureter is self-evident.

HEX20 Fig. 2. An acute granuloma abutting into the lumen in the region of the ureteric orifice. The narrowing of the lumen is apparent.

HEX20 Fig. 3. Acute bilharzia! granulomatous lesion involving all layers of the lower third of the ureter. The complete destruction of the normal architecture is evident.

HEX20 Fig. 4. Histology of a stenotic lesion at the ureteric orifice reveals whorls of dense scar tissue formed around clusters of calcified ova. The muscle is atrophic and replaced by tissue.

HEX20 Fig. 5. I.V.P. study demonstrating bilateral "cobra-head" eformity produced by stenotic lesions.

Fig. 6. I.V.P. appearances of long standing ureteric Fricture with gross hydroureter and hydronephrosis.

Fig. 7. Bilharzia! ureteritis with orate deposits. This could form the nidus of a ureteric calculus.

HEX20 Fig. 8. Histological example of chronic bilharziasis with

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Hutch, J.A., Ayres, R .D . & Loquvam, G.S. (1961J: J. Urol., 85: 531.

Ibrahim, A.B. (1923): Lancet, 2: 1184. Kirkaldy-Willis (1948): E. Afr. m.j . 25: 333. Kisner, C.D. (1952): "Vesical Bilharziasis in South

Africa" ; Unpublished Thesis, Witwaterstand University.

Makar, N. (1948): Brit. J. Sug. 36: 148. Marcks, C. (1956): S. Afr. Practit., 1: 460. Mathiesen, W. (1964): Surg. Gynae. Obstet., 118: 965. Powell, S.J. (1967): S. Afr. m.j. 41: 991. Raghab, M. (1939) : Brit. J. Radio!., 12: 21. Sayegh, E.S. (1950): J. Urol. 63: 353. Simpson, T.R. (1963): C. Afr. J. Med., 9: 364. Vermooten, V. (1937): J. Urol., 38 : 430. Zinner, N .R ., Foster, E.A., Spalding, B.H. & Paquin

A.J. (1963): J. Urol., 90: 405.

ACKNOWLEDGEMENTS

I wish to thank Prof. D. S. Chapman, Head of the Department of Surgery, University of Natal, for facilities for the clinical study and for his guidance; Dr. R . Elsdon Dew for his patience and valuable criticism ; Prof. J, Wainwright, Head of the Department of Pathology, for his invaluable guidance; Dr. H. Engelbrecht for assist­ance in interpretation of X-Rays and Dr. T. M. Adnams former Sup3rintendent of King Eduard VIII Hospital for facilities. This work was partly financed by a generous Grant from Roche Products.

myriads of calcified ova in all layers of the bladder wall, There is considerable destruction of the muscle fibres.

HEX20 Frig. 9. Stage of chronic fibrotic bilharziasis in the U/V anea. The dense whorls of scar tissue are prominent with interruption and destruction of the muscle fibres.

Masson's TrichromeX20 Fig. 10. I.V.P. demonstrating dilatation and tortuosity especially marked in the upper third.

Fig. 11. I.V.P. pattern of segmental bilharzia! hydroureter, • due to focal segmental disturbance of muscular wall of • ureter.

Fig. 12. Stage of chronic bilharziasis with plaques of bilharzia! eggs and considerable atrophy and destruction of the muscle layers.

HEX20 Fig. 13. Another example of chronic bilharziasis with masses of calcified ova separating and splitting the muscle layers with consequent atrophy and fibrosis. Myogenic paralysis is the inevitable end result.

HEX20 Fig. 14. Scout X-Ray demonstrating a calcified bladder and calcified ureters. The histological appearance of such a ureter is as demonstrated in Fig. 14.

Fig. 15. I.V.P. demonstrating bilateral hydroureter and hydronephrosis with tortuosity. Ureteric catheterisation failed to demonstrate strictures.

MEDICAL JOURNAL OF ZAMBIA July , 1969