بسم الله الرحمن الرحيم ( وقل ربي زدني علما )

1. بسم الله الرحمن الرحيم ( وقل ربي زدني علما )

2. VESICOURETERIC REFLUX Dr.NaifAlqarni K.F.H;J

3. DEFINITION A retrograde flow of bladder urine into the upper urinary tract.

4. DEMOGRAPHICS Prevalence - 10% in general population. - 70% in infants with UTI. - 30% in children with UTI - 15-25% asymptomatic infants with Antenatal hydronephrosis.

5. GENDAR - VUR usually high grade and bilateral in boys compared with girls. - Seventy six percent of refluxing infants in male ( Ring et al, 1993 ). - Even though the great majority (85%) of prevailing reflux in older children occurs in females.

6. DEMOGRAPHIC Age Incidence of Reflux in Patients with Urinary Tract Infections Age (yr) Incidence (%) <1 70 4 25 12 15 Adults 5.2

7. INHERITANCE AND GENETICS Sibling Reflux - The prevalence of VUR in siblings to be approximately 32% ( Hollowell and Greenfield, 2002 ). - Screening? - 75% are asymptomatic.

8. INHERITANCE AND GENETICS Sibling Reflux Reach to 100% in identical twin siblings; (Kaefer et al, 2000 ) The genetic mode of transmission may be autosomal dominant.

9. INHERITANCE AND GENETICS Genes Involved A prospective screen of the progeny of refluxing patients revealed a 66% rate of reflux in the offspring ( Noe et al, 1992 ), PAX 2 , chromosome 10q: mutations involving renal anomalies (dysplasia, hypoplasia) and VUR.

10. INHERITANCE AND GENETICS Genes Involved Glial-derived neurotrophic factor (GDNF) and it’s receptor RET: over expression of RET in mice leads to abnormal placement of the ureteral bud with 30% VUR at birth.

11. INHERITANCE AND GENETICS Genes Involved Uroplakin III gene (UPK3) depletion: only in animal and fatal in humans. Angiotensin receptor 2 (AGTR2): implicated in renal and ureteral developmental anomalies (UPJ obstruction, Megaureter).

12. FUNCTIONAL ANATOMY OF THE ANTIREFLUX MECHANISM A balance of several factors; 1- functional integrity of the ureter UVJ allow intermittent passage of a urinary bolus fashion from the ureter into the bladder and prevent the retrograde flow of bladder urine back toward the upper tracts during storage and micturition.

13. FUNCTIONAL ANATOMY OF THE ANTIREFLUX MECHANISM 2-anatomic composition of the UVJ The ureter enters the bladder wall with an oblique intramural path (intramural ureter) and extends through a submucosal tunnel of appropriate length (submucosalureter) to open onto the trigone in a correct location.

14. FUNCTIONAL ANATOMY OF THE ANTIREFLUX MECHANISM 2-anatomic composition of the UVJ At the extravesical bladder hiatus, the three muscle layers of the ureter separate, The outer ureteral muscle merges with the outer detrusor muscle to form Waldeyer's sheath. The latter contributes to formation of the deep trigone. The middle circular ureteral muscle ends at the level of the hiatus. The inner longitudinal ureteral fibers form the superficial trigone.

15. FUNCTIONAL ANATOMY OF THE ANTIREFLUX MECHANISMThe intramural ureter remains passively compressed by the bladder wall during bladder filling to prevent urine from entering the ureterFlap-valve’ .Adequate intramural length plus fixation of the ureter between its extravesical and intravesical points is required to create this antirefluxing compression valve.

16. The UVJ in children revealed an approximate 5:1 ratio of tunnel length to ureteral diameter in nonrefluxing junctions versus a 1.4:1 ratio in refluxing UVJs ( Paquin, 1959 ).

17. I.U.L: intravesialureteral length S.U.L:submucosalureteral length U.D: ureteraldeameter at UVJ Mean Ureteral Tunnel Length and Diameter in Normal Children Age (yr) I.U.L (mm) S.U.L (mm) U.D at UVJ (mm) 1-3 7 3 1.4 3-6 7 3 1.7 6-9 9 4 2.0 9-12 12 6 1.9 From Paquin AJ: Ureterovesicalanastomosis: The description and evaluation of a technique. J Urol 1959;82:573.

18. FUNCTIONAL ANATOMY OF THE ANTIREFLUX MECHANISM3-functional compliance of the bladderThe existence of local efferent and afferent neuromuscular coordination between the UVJ and the periureteric bladder wall is suggested by neurophysiologic studies that induce an elevation or decrease in intraluminal UVJ pressure during bladder filling ( Shafik, 1996 ).

19. ETIOLOGY OF VESICOURETERAL REFLUXPrimary RefluxRepresents a congenital defect in the structure and therefore the function of the UVJ. Reflux occurs despite an adequately low-pressure urine storage profile in the bladder. The length-diameter ratio of the intramural ureteral tunnel is almost always less than 5:1 ratio.

20. ETIOLOGY OF VESICOURETERAL REFLUX Secondary reflux In normal, mature urinary tract, increasing the intravesical pressure alone does not necessarily induce VUR.

21. ETIOLOGY OF VESICOURETERAL REFLUX Secondary reflux Secondary obstruction can be due to anatomical; ureterocele, uretheralstenosis or PUV. OR functional ; neurogenic bladder, non-neurogenicneurogenic bladder, bladder instability.

22. ETIOLOGY OF VESICOURETERAL REFLUX Secondary reflux Anatomical Causes of Secondary Reflux; PUV: Most common cause, Reflux is present in 48% to 70% of patients with PUVs. Relief of PUV obstruction appears to be responsible for resolution of reflux in one third of patients only.

23. ETIOLOGY OF VESICOURETERAL REFLUX Secondary reflux Anatomical Causes of Secondary Reflux; In females, anatomic bladder obstruction is rare. The most common structural obstruction is from a ureterocele that prolapses into the bladder neck ( Merlini and LelliChiesa, 2004 )

24. ETIOLOGY OF VESICOURETERAL REFLUX Secondary reflux Functional causes Poorly compliant bladder along with its abnormal interaction with dyssynergic urinary sphincters can lead to increase interavesical pressures which then weakens and alters the UVJ to cause VUR. McGuire established a strong correlation of bladder pressure more than 40 cmH2O with VUR raised to 80% in patients with neurogenic bladder.

25. ETIOLOGY OF VESICOURETERAL REFLUX Secondary reflux Functional causes Increase in bladder voiding pressures, continence is exchanged for incomplete emptying. Gradual distortion of bladder and UVJ architecture. Structural failure of the UVJ is a critical determinant in creating secondary VUR.

26. ETIOLOGY OF VESICOURETERAL REFLUX Secondary reflux Functional Causes of Secondary Reflux; UTI: ureteralatony lessens compliance, increases intravesical pressures, distorting and weakening the UVJ ; transient VUR can appear during UTI and resolve after treatment.

27.  International Classification of Vesicoureteral Reflux Grade Description IInto a nondilatedureter. II Into the pelvis and calyces without dilatation. III Mild to moderate dilatation of the ureter, renal pelvis, and calyces with minimal blunting of the fornices. IV Moderate ureteraltortuosity and dilatation of the pelvis and calyces. V Gross dilatation of the ureter, pelvis, and calyces; loss of papillary impressions; and ureteraltortuosity.

29. DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX - Antenatal hydronephrosis. - UTI. - Fever; VUR present in 56% of patients less than 6months and temp. 38.5. Renal scarring can occur with a single UTI, even in the absence of a fever.

30. DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX Radiographic investigation for VUR has generally been directed to; - Children with UTI and younger than 5 years, - All children with a febrile UTI regardless of age, - Any male with a UTI regardless of age or fever.

31. DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX ASSESSMENT OF THE LOWER URINARY TRACT Cystographic Imaging The basis of reflux detection lies in demonstrating the retrograde passage of an imaging contrast material from the bladder to the ureter and pelvicalyceal system.

32. DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX ASSESSMENT OF THE LOWER URINARY TRACT Cystographic Imaging VCUG -provides information on both the functional dynamics and the structural anatomy of the urinary tract. -Static images record bladder contour, the presence of diverticula or ureteroceles, the grade of reflux, the configuration and blunting of calyces, and intrarenal reflux. -Passive or active reflux is demonstrated dynamically during fluoroscopy while filling and voiding.

33. Normal VCUG

34. Grad V VUR

35. PUV

36. DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX ASSESSMENT OF THE LOWER URINARY TRACT Cystographic Imaging Radionuclide Cystogram: - Reduces radiation exposure. - More sensitive in some cases. - Greater role in follow up. - Bladder wall trabeculation, diverticuli, ureteral duplications and posterior urethral valve cannot be seen.

39. DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX ASSESSMENT OF THE upper URINARY TRACT Renal Sonography - Nonionizing, noninvasive imaging platform - Quantitative assessment of renal dimensions, which can then be used to monitor renal growth over time.

40. u/s Rt. Kidney in pt. with g II reflux In Rt. Duplex system

41. DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX ASSESSMENT OF THE upper URINARY TRACT Di-mercapto-succinic acid (DMSA); - The gold standard for imaging functioning renal parenchyma. - Document congenital dysplasia. - Assessment of renal growth and development - Need 2 studies separated by 8-12 weeks to differentiate pyelonephritis from scar.

42. Normal DMSA

43. Left kidney scar

44. Sever scared Rt. kidney

45. DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX ASSESSMENT OF THE UPPER URINARY TRACT Magnetic Resonance Imaging: - Used with gadolinium based contrast material. - Diagnose reflux, and assess renal parenchymal scarring. - Catheter to introduce contrast. - Not sensitive. - Need sedation. - Child cannot void during study.

46. CORTICAL DEFECTS Renal scarring CongenitalRenal Scarring   Grade of VUR Normal Slight Damage Severe Damage I-III 13 (100%) IV 8 (53%) 5 (34%) 2 (13%) V 2 (15%) 5 (38%) 6 (46%) Adapted from Marra G, Barbieri G, Dell'Agnola CA, et al: Congenital renal damage associated with primary vesicoureteric reflux. Arch Dis Child Fetal Neonatal Ed 1994;70:F147.

47. CORTICAL DEFECTS Acquired Renal Scarring Reflux provides a mechanical hydrodynamic mechanism that facilitates the ascension of micro-organisms from the bladder to the kidneys. As such, reflux may be considered an accelerant for renal tissue infection after bacterial colonization of the bladder.

48. Factors important for acquired renal scarring; Grade The frequency of scarring itself appears to be directly proportional to the grade of reflux with which it is associated ( Winter et al, 1983 ; Weiss et al, 1992b ). Age The greatest risk for postinfectious renal scarring occurs within the first year of life ( Winberg, 1992 ). The kidney's predilection for postpyelonephritic scarring is inversely proportional to age. Scarring may still occur beyond 5 years of age ( Smellie et al, 1985 ; Benador et al, 1997 ).

49. Factors important for acquired renal scarring; Age scarring in older children is frequently the result of late diagnosis, delayed or inadequate treatment of infection, and social factors that often interfere with patient management. Adults with pyelonephritis and normal urinary tract rarely have scarring.

50. Complication of renal scarring; Hypertension, - 10-20% of children with reflux nephropathy. - Related to reflux grade, scarring severity and bilaterality. - Correction of reflux alone is unlikely to ameliorate blood pressure ( Wallace et al, 1978 ).