Pathophysiology of Urinary Tract Obstruction

1. Pathophysiology of Urinary Tract Obstruction Jamie Bartley D.O. PGY 3..almost 4 5/27/09 MSU-COM Metro Detroit Urology

2. Outline • I. Background • II. Pathophysiology and pathological changes with urinary tract obstruction • III. Patient work-up and management • IV. Causes of urinary tract obstruction

3. Definitions • Hydronephrosis- Dilation of the renal pelvis or calyces • Obstructive uropathy- functional or anatomic obstruction of urine flow at any level of the urinary tract • Obstructive nephropathy- when obstruction causes function or anatomic renal damage

4. Prevalence • 3.1% in autopsy series • No gender differences until 20 years • Females more common 20-60 • Males more common older than 60 • 2-2.5% of children at autopsy

5. Causes of Obstructive Nephropathy • Table 37-1 -- Possible Causes of Obstructive Nephropathy • Renal- • Congenital, Polycystic kidney, Renal cyst, Fibrous obstruction at ureteropelvic junction, Peripelvic cyst, Aberrant vessel at ureteropelvic junction • Neoplastic- Wilms' tumor, Renal cell carcinoma, Transitional cell carcinoma of the renal pelvis, Multiple myeloma • Inflammatory- Tuberculosis, Echinococcus Infection • Metabolic- Calculi • Miscellaneous- Sloughed papillae, Trauma, Renal artery aneurysm • Ureter • Congenital- Stricture, Ureterocele, Ureterovesical reflux, Ureteral valve, Ectopic kidney, Retrocaval ureter, Prune-belly syndrome • Neoplastic- Primary carcinoma of ureter, Metastatic carcinoma • Inflammatory- Tuberculosis, Schistosomiasis, Abscess, Ureteritis cystica, Endometriosis • Miscellaneous- Retroperitoneal fibrosis, Pelvic lipomatosis, Aortic aneurysm, Radiation therapy, Lymphocele, Trauma, Urinoma, Pregnancy • Bladder and Urethra • Congenital- Posterior urethral valve, Phimosis, Urethral stricture, Hypospadias and epispadias, Hydrocolpos • Neoplastic- Bladder carcinoma, Prostate carcinoma, Carcinoma of urethra, Carcinoma of penis • Inflammatory- Prostatitis, Paraurethral abscess • Miscellaneous-Benign prostatic hypertrophy, Neurogenic bladder

6. Global Renal Functional Changes • Obstruction can affect hemodynamic variables and GFR • Degree of affect depends on extent and severity of obstruction, whether UUO or BUO, and whether it has been relieved or not • GFR= Kf(PGC-PT-PGC) • Need to understand in order to comprehend the relationships between changes in renal hemodynamics and alterations in GFR during and after obstruction • RPF= (aortic pressure-renal venous pressure) renal vascular resistance • Influences PGC • Constriction of the afferent arteriole will result in a decrease of PGC and GFR • An increase in efferent arteriolar resistance will increase PGC • Kf- flomerular ultrafiltration coeffecient related to the surface area and permeability of the capillary membrane • PGC- glomerular capillary pressure. Influenced by renal plasma flow and the resistance of the afferent and efferent arterioles • PT- Hydraulic pressure of fluid in the tubule • P- the oncotic pressure of the proteins in the glomerular capillary and efferent arteriolar blood

7. Hemodynamic Changes with Unilateral Ureteral Occlusion • Triphasic patternof renal blood flow and ureteral pressure changes • 1. RBF increases during the first 1-2 hours and is accompanied by a high PT and collecting system pressure • 2. For another 3-4 hours, the pressures remains elevated but the RBF begins to decline • 3. 5 hours after obstruction, further decline in RBF occurs. A decrease in PT and collecting system pressure also occurs

8. Triphasic pattern of UUO

9. Hemodynamic Changes with Unilateral Ureteral Occlusion • Alterations in flow dynamics within the kidney occur dye to changes in the biochemical and hormonal milieu regulating renal resistance • Phase I- The increased PT is counterbalanced by an increase in renal blood flow via net renal vasodilation, which limits the fall of GFR • PGE2, NO – Contribute to net renal vasodilation early in UUO • Phase II and III- An increase in afferent arteriolar resistance occurs causing a decrease RPF. A shift in RBF from the outer cortex to the inner cortex also occurs all reducing GFR • Angiotensin II, TXA2, Endothelin - mediators of the preglomerular vasoconstriction during the 2nd and 3rd phase of UUO

10. Hemodynamic Changes with Bilateral Ureteral Occlusion • Only a modest increase in RBF lasting 90 minutes followed by a prolonged and profound decrease in RBF that is even more than with UUO • The intrarenal distribution of blood flow changes from the inner to the outer cortex (opposite from UUO) • Accumulation of vasoactive substances (ANP) in BUO that contributes to preglomerular vasodilation and postglomerular vasoconstriction • With UUO, these substances would be excreted by the normal kidney • When obstruction is released, GFR and RBF remain depressed due to persisent vasoconstriction of the afferent arteriole • The post-obstructive diuresis is much greater than with UUO

11. Summary of UUO and BUO

12. Partial Ureteral Occlusion • Changes in renal hemodynamics and tubular function are similar to complete models of obstruction • Develop more slowly • Animal Studies- Difficult to imitate partial obstruction • 14 days- normal functional recovery • 28 days- recover 31% of function • 60 days- recovery 8% of function

13. Effects of Obstruction on Tubular Function • Dysregulation of aquaporin water channels in the proximal tubule, thin descending loop, and collecting tubule • Lead to polyuria and impaired concentrating capacity • Sodium Transport • Decreased which leads to a role in the postobstructed kidney’s impaired ability to concentrate and dilute urine • Much greater sodium and water excretion after release of BUO than UUO • Thought to be due to the retention of Na, water, urea nitrogen and increased ANP, all which stimulate a profound naturesis • Potassium and phosphate excretions follow changes in sodium • Decreased with UUO • Increased transiently with BUO in parallel with the massive diuresis • Deficit in urinary acidification • Magnesium excretion is increased after release of UUO or BUO • Changes in pepetide excretion mark renal damage

14. Cellular and Molecular Changes lead to Fiborosis and Tubular Cell Death • Obstruction leads to biochemical, immunologic, hemodynamic, and functional changes of the kidney • A cascade of events occur which lead to release of angiotensin II, cytokines, and growth factors (TGF-B, TNF-a, NFkB) • Some mediators are produced directly from the renal tubular and interstitial cells • Others are generated by way of fibroblasts and macrophages • Progressive and permanent changes to the kidney occur • Tubulointerstitial fibrosis • Tubular atrophy and apoptosis • Interstitial inflammation

15. Pathologic Changes of Obstruction(porcine model) • Gross Pathologic Changes • 42 hours- Dilation of the pelvis and ureter and blunting of the papillary tips. Kidney also heavier • 7days- Increased pelviureteric dilation and weight. Parenchyma is edematous • 21-28 days- External dimensions of kidneys are similar but the cortex and medullary tissue is diffusely thinned • 6 weeks- Enlarged,cystic appearing, weighs less than non-obstructed kidney • Did not see such differences in partially obstructed kidneys

16. Pathologic Changes of Obstruction(porcine model) • Microscopic Pathologic Findings • 42 hours- Lymphatic dilation, interstitial edema, tubular and glomerular preservation • 7 days- Collecting duct and tubular dilation, widening of Bowman’s space, tubular basement membrane thickening, cell flattening • 12 days- Papillary tip necrosis, regional tubular destruction, inflammatory cell response • 5-6 weeks- widespread glomeular collapse and tubular atrophy, interstitial fibrosis, proliferation of connective tissue in the collecting system

17. Compensatory Renal Growth • Enlargement of the contralateral kidney with unilateral hydronephrosis or renal agenesis • A reduction in compensatory growth occurs with age • An increase in the number of nephrons or glomeruli does not occur, despite enlargement

18. Renal Recovery after Obstruction • Degree of obstruction, age of patient, and baseline renal function affect chance of recovery • Two phases of recovery may occur • Tubular function recovery • GFR recovery • Duration has a significant influence • Full recovery of GFR seen with relief of acute complete obstruction • Longer periods of complete obstruction are associated with diminished return of GFR • DMSA scan is predicative of renal recovery

19. Now on to the Clinical Stuff…

20. Management of Patients with ObstructionDiagnostic Imaging • Renal US • Safe in pregnant and pediatric patients • Good initial screening test • No need for IV contrast • May have false negative in acute obstruction (35%) • Hydronephrosis= anatomic diagnosis • Can have caliectasis or pelviectasis in an unobstructed system • Doppler- measures renal resistive index (RI), an assessment of obstruction • RI= (PSV-EDV)/PSV • RI > 0.7 is suggestive elevated resistance to blood flow suggesting obstructive uropathy

21. Excretory Urography Applies anatomic and functional information Limited use in patients with renal insufficiency Increased risk of contrast-induced nephropathy Cannot use in patients with contrast allergy Diagnostic Imaging

22. Retrograde Pyelography Gives accurate details of ureteral and collecting system anatomy Good if renal insufficiency or other risks for contrast Loopogram- use for evaluation of patients with cutaneous diversions Antegrade Pyelography Can do if RGP is not possible and other imaging doesn’t offer enough details Diagnostic Imaging

23. Diagnostic Imaging • Whitaker Test • “True pressure” within the pelvis = Collecting system pressure – intravesicle presure • Saline or contrast though a percutaneous needle or nephrostomy tube at a rate of 10mL/ min • Catheter in bladder to monitor intravesicle pressure • Invasiveness and discordant results limit clinical usefulness Normal < 15 cm H2OIndeterminate = 15-22 cm H2OObstruction > 22 cm H2O

24. Diagnostic Imaging • Nuclear Renography • Provides functional assessment without contrast • Obstruction is measured by the clearance curves • Tc 99m DTPA- glomerular agent • Tc 99m MAG3 – tubular agent • Diuretic renogram- maximizes flow and distinguishes true obstruction from dilated and unobstructed Normal = T ½ < 10 minIndeterminate = T ½ 10-20 minObstructed T ½ > 20 min

25. CT Most accurate study to diagnose ureteral calculi More sensitive to identify cause of obstruction Helpul in surgical planning **Preferred initial imaging study in those with suspected ureteral obstruction MRI Can identify hydro but unable to identify calculi and ureteral anatomy of unobstructed systems Diuretic MRU can demonstrate obstruction Especially accurate with strictures or congential abnormalities IV gadopentetate-DTPA allows functional assessment of collecting system while providing anatomic detail GFR assessment Renal clearance Still several limitations in its use Diagnostic Imaging

26. Issues in Patient Management • Hypertension • Can be caused by ureteral obstruction • Especially BUO or obstruction of a solitary kidney • Less common with UUO • Volume-mediated • Increased ANP with obstruction which normalizes after drainage • Decreased plasma renin activity

27. Issues in Patient Management • Renal Drainage • Endourologic or IR procedures allow prompt temporary and occasionally permanent drainage • No statistically significant difference in HRQL between the two techniques • Patients with extrinsic compression causing obstruction have a high risk of ureteral stent failure • 42-56.4 % failure rate at 3 months • 43% failed within 6 days of placement in one study • High failure rate at even getting placement(27%) • Stent diameter did not predict risk of failure • Ultrasound guided percutaneous drainage should be initial consideration in pregnant patients • Percutaneous placement with suspected pyonephrosis • Large diameter ureteral stents

28. Issues in Patient ManagementConsiderations in Surgical Intervention • Reconstruction • Endoscopic, open and laparoscopic techniques should be considered • Need for nephrectomy? • Allow 6-8 weeks for adequate drainage before proceeding • Nuclear imaging provides accurate functional information • < 10% contribution to global renal function is considered threshold for nephrectomy

29. Issues in Patient ManagementPain • Increases in collecting system pressure and ureteral wall tension contribute to renal colic • Results in spinothalamic C-fiber excitation • Treating Pain • Narcotics • Rapid onset, nausea, sedation, abuse • NSAIDS • Targets the inflammatory basis of pain by inhibiting prostaglandin synthesis • Reduces collecting system pressure by decreasing renal blood flow • Avoid in patients with renal insufficiency, GI bleeds

30. Issues in Patient ManagementPostobstructive Diuresis • Usually with BUO or solitary kidney • Urine output > 200ml/hour • A normal physiologic response to volume expansion and solute accumulation • Elimination of sodium, urea, and free water • Diuresis ends when homeostasis returns • Pathologic postobstructive diuresis • Impaired concentating abilility or sodium absorption • Downregulation of sodium transporters and sodium reabsorption in the thick ascending loop of Henle • Increased production and altered regulation of ANP • Poor response of collecting system to ADH

31. Issues in Patient ManagementPostobstructive Diuresis • Management • Monitor those with BUO or UUO in solitary kidney for POD • Electrolytes, Mg, BUN, Cr • Intensity of monitoring depends on clinical factors • If no signs of POD If alert, no fluid overload, normal renal function, normal lytes,  discharge and follow up • If signs of POD  If alert, able to consume fluids, normal VS continue in-patient observation, free access to oral fluids, and daily labs until diuresis resolves (No IV Fluids) • If signs of POD and signs of fluid overload, poor renal function, hypovolemia, or MS changes Frequent VS and u.o records, labs q 12 hrs (or more), urinary osmolarity, restrict oral hydration (Minimal IV fluid hydration) • Most have self-limiting physiologic diuresis • If pathologic diuresis occurs- very intense monitoring is indicated

32. Selected Causes of Extrinsic Ureteral Obstruction

33. Retroperitonal Fibrosis • Condition in which an inflammatory mass, a fibrous whitish plaque, envelops and potentially obstructs retroperitoneal structures • Usually extends from the renal hilum to pelvic brim • May involve the mediastinum and the pelvis • 2 phases lead to its development 1. Autoimmune reaction thought to occur due to leakage of ceroid from the atheromatous plaques in the aorta • Local inflammatory reaction characterized by plasma cells, lymphocytes, macrophages, eosinophils 2. Fibrotic maturation with development of homogeneous fibrous tissue with limited cellularity

34. Retroperitoneal Fibrosis • 1: 200,000, 3:1 Male: Female, Age 50 • 2/3s of Cases are “Idiopathic” • 8-10% of cases have underlying malignancy • Other causes: Medications (methysergide, hydralazine, Haldol, B-Blockers, LSD, Phenacetin, Amphetamines), RP hemorrhage, urinary extravasation, trauma, radiation, IBD, Gonorrhea, collagen disease, peri-aneurysmal inflammation • Symptoms- Dull, non-colicky pain in a “girdle” distribution, ureteral or vascular obstruction (late)

35. Retroperitoneal Fibrosis • Diagnosis • IVP- Medial deviation of the ureters • Can be seen in 18% of normal subjects • CT – well demarcated mass that is isodense with muscle (non-contrast study) • MRI- Allows superior soft tissue discrimination and can more accurately distinguish the plaque from the great vessels

36. Diagnosis of Retroperiteoneal Fibrosis

37. Retroperitoneal Fibrosis • Treatment 1. Correct obstructive uropathy 2. Biopsy to exclude malignancy 3. If biopsy is negative, medical therapy is preferred • Discontinue any offending medications • Corticosteroids- prednisolone 60mg qod x 2 mos, tapered to 5mg daily over the next 2 months, then continue 5mg daily for 2 years • Tamoxifen • Immunotherapy 4. Ureterolysis- if patient not a candidate for medical therapy or if it fails - May do open or laparoscopic - Bilateral treatment is recommended even if unilateral disease - To prevent recurrent ureteral involvement bring ureter intraperitoneal, or wrap in omentum - Stents can usually be removed 6-8 wks after ureterolysis Experimental

38. Pelvic Lipomatosis • Rare benign proliferative disease involving the mature fatty tissues of the pelvic retroperitoneum • 18:1 Male to female • More common in African American men • Unknown etiology • Obesity? • Genetic?

39. Pelvic Lipomatosis • Patient Presentation and Diagnosis • LUTS, Constipation, non-specific pain, HTN • Physical Exam- suprapubic mass, high riding prostate, indistinct pelvic mass • Younger patients are thought to have a more progressive course than older patients who have a more indolent course

40. Pelvic Lipomatosis • Imaging • KUB- Pelvic lucency • IVP- Bladder is pear-shaped and elevated, hydronephrosis may be evident • CT- pelvic fat is readily demonstrated

41. Pelvic Lipomatosis • Other evaluation • Cystoscopy- cystitis cystica, cystitis glandular (40%), adenocarcinoma, chronic UTI • High bladder neck, pelvic fixation, and elongated prostatic urethra may impair rigid cystoscopy • Treatment • Exploration is not recommended due to the obliteration of normal planes and increased vascularity of the mass • In patients with obstructive uropathy stents, PCNs, ureteral reimplanation, urinary diversion

42. Pregnancy • Reported to occur in 43-100% • Right > Left • Etiology • Hormonal- progesterone thought to promote ureteral dilation • Mechanical – increased degree of dilation after 20 weeks when the uterus reaches the pelvic brim

43. Pregnancy • Diagnosis • Usually asymptomatic • If symptoms, may have flank pain or pyelonephritis • US will show dilation to the pelvic brim • If it extends below this, consider other etiologies (stone) • Limited IVU or MRI to diagnose • Treatment • Most respond to conservative treatment • IVF, analgesics, antibiotics • If signs of sepsis or compromised renal function may need ureteral stents or nephrostomy tubes

44. Endometriosis • GU involvement • Bladder 70-80% • Ureter 15-20% • May be intrinsic or extrinsic (80%) • Cyclical flank pain, dysuria, urgency, UTI, hematuria, or no GU symptoms (silent loss of renal function may occur) • Recommended to image the Upper tracts in all patients with pelvic endometriosis (RUS or EXU)

45. Endometriosis • Treatment • Hormone therapy- if normal renal function with mild hydro and no functional obstruction seen on renogram • GnRH agonists • Surgery- treatment of choice for patients with significant disease • TAH with BSO • Unilateral oopherectomy • Ureterolysis if extrinsic disease • Distal ureterectomy with reimplantation

46. Vascular Causes of Ureteral Obstruction • Abdominal Aortic Aneurysm • Ureteral obstruction may be the first sign • Medial deviation of the ureters associated with the desmoplastic reaction of inflammatory AAA (IAAA) more likely to cause obstruction than lateral deviation • Stent placement usually recommended prior to aneurysmal repair • Ureterolysis usually not needed and obstruction resolves with correction of the aneurysm

47. Circumcaval Ureter • Anomalous course of the ureter to the IVC leading to extrinsic obstruction • Thought to be due to the persistence of the subcardinal vein as the infrarenal IVC, causing medial migration and compression of the right ureter • Other theories involve persistence of the posterior cardinal vein as the infrarenal cava • Both, theories note failure of the supracardinal vein to develop into the infrarenal IVC

48. Circumcaval Ureter

49. Circumcaval Ureter • Treatment is performed only in presence of obstruction • Divide ureter proximally and at the distal point it emerges lateral to the IVC • Spatulated ureterostomy performed

50. Other causes of vascular obstruction • Iliac Artery Aneurysm • Typically place internal ureteral stents prior to aneurysmal repair • Obstruction after Vascular Graft placement • Usually resolves spontaneously • Graft transection and repositioning • Chronic stenting • Puerperal Ovarian Vein Thrombophlebitis • Antiobiotic therapy usually resolves