Pathophysiology of Urinary Tract Obstruction

Jamie Bartley D.O. PGY 3..almost 4

5/27/09MSU-COM Metro Detroit Urology

Outline

• I. Background• II. Pathophysiology and

pathological changes with urinary tract obstruction

• III. Patient work-up and management

• IV. Causes of urinary tract obstruction

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

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

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

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-GC)– 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 membranePGC- glomerular capillary pressure. Influenced by renal plasma flow and the resistance of the afferent and efferent arteriolesPT- Hydraulic pressure of fluid in the tubule- the oncotic pressure of the proteins in the glomerular capillary and efferent arteriolar blood

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

Triphasic pattern of UUO

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

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

Summary of UUO and BUO

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

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

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-, TNF-, NF)– 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

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

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

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

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

Now on to the Clinical Stuff…

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

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

Diagnostic Imaging

• 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

• 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 usefulnessNormal < 15 cm H2O Indeterminate = 15-22 cm H2O Obstruction > 22 cm H2O

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 10-20 min Obstructed T ½ > 20 min

Diagnostic Imaging

• 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

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

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

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

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

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

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

Selected Causes of Extrinsic Ureteral Obstruction

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 development1. 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

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)

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

Diagnosis of Retroperiteoneal Fibrosis

Retroperitoneal Fibrosis

• Treatment1. Correct obstructive uropathy2. Biopsy to exclude malignancy3. 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

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?

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

Pelvic Lipomatosis• Imaging

– KUB- Pelvic lucency– IVP- Bladder is pear-shaped and elevated,

hydronephrosis may be evident– CT- pelvic fat is readily demonstrated

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

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

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

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)

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

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

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

Circumcaval Ureter

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

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