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 pattern of 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 Obstruction Diagnostic 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. Diagnostic Imaging 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

22. Diagnostic Imaging Retrograde Pyelography Antegrade 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

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 H2O Indeterminate = cm H2O Obstruction > 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 min Indeterminate = T ½ min Obstructed T ½ > 20 min

25. Diagnostic Imaging MRI CT
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 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

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
% 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 Management Considerations 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 Management Pain
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 Management Postobstructive 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 Management Postobstructive Diuresis
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 Treatment
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 Treatment 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