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Giriş ve amaç: İntraabdominal basınç (İAB) artışının üriner sistemde anatomik ve işlevsel anormalliklere yol açabileceği öne sürülmüş ve artmış intraamniotik basıncın (İAMNB) fetüs mesanesinin kasılma özelliklerini değiştirdiği gösterilmiştir. Bu çalışma, tavşan fetüslerinde İAMNB artışının üriner sistem gelişimine etkilerini incelemek amacıyla kurgulanmıştır.

Gereç ve yöntem: Dokuz tane gebe Yeni Zelanda tavşanı kullanıldı. Kontrol (KG, n=5) ve deney grubu (DG, n=4) tavşanlara gebeliğin 15. gününde intraperitoneal kateter yerleştirildi. 20. günden başlayarak terme kadar (30.gün) İAB 17cmHO olacak şekilde pnömoperiton uygulamaları yapıldı. Gebeliğin sonunda fetüs vücut ağırlığı (VA), total böbrek ağırlığı (TBA) ve mesane ağırlığı (MA) ölçüldü, TBA/VA ve MA/VA oranları hesaplandı. Organ histolojisi ve apopitoz (TUNEL yöntemi) incelendi.

Bulgular: 27 fetüs (KG; n=10, DG; n=17) değerlendirildi. KG ve DG karşılaştırıldığında; DG fetüslerde VA (38,65 ± 8,34g ve 49,36 ± 8,81g; p=0,008 ), TBA (0,406 ± 0,132g ve 0,531 ± 0,129g; p=0,02), MA  (0,067 ± 0,014 ve  0,114 ± 0,026g; p=0,00) ve MA / VA oranı (0,00175 ± 0,00026 ve 0,00229 ± 0,00036; p=0,001) artmış, TBA / VA oranı değişmemiştir (0,0103 ± 0,001 ve 0,0107 ± 0,001; p=0,33). Deney grubu böbreklerde; kortekste glomerüllerin daha immatür ve az gelişmiş olduğu görülmüş, medullada toplayıcı tübül epitelinde bazal vakuoller ve apikal çekirdek, ödem ve staz oluşmuş, ayrıca glomerül ve tübül hücrelerinde apopitoz (p<0,05 ve p<0,05) artmıştır. Deney grubu üreterlerde; kas tabakasının inceldiği, adventisyada konjesyone damarlar olduğu, epitel hücrelerinde ve daha belirgin ve yaygın olarak kas tabakasında apopitozun arttığı saptanmıştır (p=0,002 ve p=0,02). Deney grubu mesanelerde; epitelin döküldüğü, bağ dokusunun az gelişmiş kas tabakası ve mezenşimal hücreler içerdiği, kas tabakasında apopitozun arttığı (p=0,004) ve çoğu epitel hücresinin apopitotik olduğu (p=0,043) bulunmuştur.

Sonuç ve yorum: Gebeliğin son trimesterinde İAMNB’ ın artması fetüs üriner sistem gelişimini olumsuz etkilemektedir. Böbrek parankimi, üreter ve mesane kas tabakaları gelişimi bozulmaktadır. Bu gözlemler İAMNB artışının hipoplastik/displastik böbrek, hidroüreteronefroz ve primer megaüreter, megasistis, nonnörojenik nörojenik mesane, işeme disfonksiyonu ve bazı doğmalık karmaşık hipoperistaltik üriner sistem patolojilerinin etyopatogenezinde rolü olabileceğini akla getirmektedir. Üriner sistem gelişiminin kritik evrelerinde İAMNB artışının etkileri daha ağır olabilir.

Background/Purpose: It has been previously suggested that increased intraabdominal pressure (IAP) may predispose development of various types of anatomic and functional abnormalities in the urinary system. Additionally increased intraamniotic pressure (IAMNP) has been proved to effect on contractile properties of the fetal bladder. An intrauterine experiment was conducted to investigate the effects of increased IAMNP on the development of urinary system in the fetal rabbits.

Materials and method: New Zealand pregnant rabbits were used for the study. Control (CG, n=5) and experiment (EG, n=4) groups animals underwent intraperitoneal catheter placement in the 15^th day of gestation. Intraperitoneal air insufflations were performed between 20 and 30 days of gestation in the EG. IAP was increased to 17 cmH₂O which generates an IAMNP of 15.6 cmH₂O. Fetuses were extracted at term (30 days) in both groups, and kidneys and bladder were weighed and placed into 10 % formalin solution. Body weight (BW), total renal weight (TRW), bladder weight (BLW), TRW / BW and BLW / BW was noted. The specimens were evaluated under light microscope by means of morphological changes and apoptosis following hematoxylen-eosin staining or TUNEL procedure respectively. Statistical analysis was performed between the mean apoptotic indexes.

Results: The morphometric data were available for 10 and 17 fetuses for CG and EG respectively. BW and TRW was significantly increased in the EG (38.65 ± 8.34 vs. 49.36 ± 8.81g; p=0.008 and 0.406 ± 0.132 vs. 0.531 ± 0.129g; p=0.02 respectively). TRW / BW ratio did not differ between groups (0.0103 ± 0.001 vs. 0.0107 ± 0.001; p=0.33). Bladder weight and BLW / BW ratio was also significantly increased in the EG (0.067 ± 0.014 vs. 0.114 ± 0.026g; p=0.00 and 0.00175 ± 0.00026 vs. 0.00229 ± 0.00036; p=0.001 respectively).

Histological examination revealed following findings; Kidneys: The gromeruli were immature and incompletely developed in the cortex, basal vacuoles and apical nuclei were seen in the collecting tubule epithelium in the medulla, in addition to interstitial edema and vascular stasis in the EG. Apoptotic cells were seen in both groups. Apoptotic cell index was significantly different in the EG (p=0,00). Ureters: The muscular layer was thin and congested vessels were encountered in the adventitia in EG. Apoptosis was present in both epithelial and muscle layers however it was much prominent and diffuse in the muscle layer in EG (p= 0.002 and p=0.020). Bladders: The lumen epithelium was exfoliated and underlying connective tissue contained underdeveloped muscle cells and mesenchymal cells and apoptosis was significantly different  in the muscle layer in EG (p=0.004) Most of the intact epithelial cells were apoptotic. Apoptotic cell index was significant (p=0,043).

Conclusion: Increased IAMNP in the last trimester of gestation results deterioration in the development of fetal urinary system. The spectrum of changes in the urinary organs varies between incomplete development of glomeruli of the kidney and muscle layers of ureters and bladder. This observation suggests that increased IAP and IAMNP may play role in the pathogenesis of various congenital abnormalities of the urinary system such as hypoplastic and/or dysplastic kidney, hydroureteronephrosis and primary megaureter, megacystis, nonneurogenic neurogenic bladder and dysfunctional voiding and some complex forms of hypoperistaltic urinary system pathologies. These findings may imply that increase in the IAMNP and thus fetal IAP during pregnancy may reveal more profound effect during the critical stages of development urinary system of the fetus.