Pathophysiology of Urinary Tract Obstruction

chapter 40Dr.Mariam MalallahDr.Abdullatif Al-Terki

Obstruction of the urinary tract

• Obstruction of the urinary tract can occur during fetal development, childhood, or adulthood.

• The point of obstruction:Proximal -> calyces Distal -> urethral meatus.

• lead to permanent renal damage limiting the excretion of metabolic wastes altering water and electrolyte balance.

• Hydronephrosis:- Is the dilation of the renal pelvis or calyces. - Associated with obstruction. - may be present in the absence of obstruction.

• Obstructive uropathy:- The functional or anatomic obstruction of urinary flow at any level of the urinary tract. - The obstruction causes:functional or anatomic renal damage.

GLOBAL RENAL FUNCTIONAL CHANGESGlomerular Filtration, Renal Blood Flow, Collecting System Pressure

• Functional changes associated with obstructive nephropathy. - Renal hemodynamic variables- Glomerular filtration.

• influenced by:- The extent and severity of obstruction- Unilateral or bilateral- Persists or has been relieved.

• Factors influencing GFR are expressed in the following equation:

GFR = Kf (PGC −PT −πGC)• Kf: glomerular ultrafiltration coefficient • PGC: glomerular capillary pressure

Influenced by:- Renal plasma flow (RPF)- The resistances of the afferent and efferent arterioles.

• The hydraulic pressure of fluid in the tubule (PT)• oncotic pressure (π) of the proteins

• RPF depends upon: - The renal perfusion pressure - Intrarenal resistance to flow is mediated by the resistances in the afferent and efferent arterioles.

RPF = aortic pressure − renal venous pressure renal vascular resistance

• Obstruction can transiently or permanently alter GFR and some or all of the determinants of GFR.

• Unilateral and bilateral ureteral obstructions differ in- the patterns of hemodynamic- ureteral pressure changes- distribution of renal blood flow.

Hemodynamic Changes with Unilateral Ureteral Occlusion

• Animal experiments have demonstrated a triphasic pattern of RBF and ureteral pressure changes in UUO

• first 1 to 2 hours-RBF increases -high PT and collecting system pressure

• second phase lasting 3 to 4 hours-pressure parameters remain elevated -RBF begins to decline.

• third phase beginning about 5 hours after obstruction -a further decline in RBF -decrease in PT and collecting system pressure.

• Triphasic relationship between ipsilateral renal blood flow and left ureteral pressure during 18 hours of left-sided occlusion. • The three phases are designated by roman numerals and separated by vertical dashed lines. • In phase I, renal blood flow and ureteral pressure rise together. • In phase II, the left renal blood flow begins to decline and ureteral pressure remains elevated and, in fact, continues to rise. • In phase III, the left renal blood flow and ureteral pressure decline together.

• It is likely that both PGE2 and NO contribute to the net renal vasodilation that occurs early following UUO.

• Thus reduced whole kidney GFR at this stage of obstruction is due not only to reduced perfusion of individual glomeruli, related to afferent vasoconstriction and reduced PGC,but also to global reduction in filtration related to no perfusion or underperfusion of many glomeruli.

Hemodynamic Changes with Bilateral Ureteral Occlusion

• A modest increase in RBF with BUO that lasts approximately 90 minutesfollowed by a prolonged and profound decrease in RBF that is greater than found with UUO.

• The intrarenal distribution of blood flow is quite different with BUO than with models of UUO.

• Thus the shift seen with UUO of blood flow from outer to inner cortex is the opposite of that with BUO.

• Ureteral pressure is higher with BUO than with UUO.

• In both cases ureteral and tubular pressures are increased for the first 4 to 5 hours. -The ureteral pressure remains elevated for at least 24 hours with BUO-The ureteral pressure begins to decline and approaches preocclusion pressures by 24 hours with UUO.

• This difference between the two pathophysiologic

conditions has been hypothesized to be

-due to an accumulation of vasoactive substances in BUO that could contribute to preglomerular vasodilation and postglomerular vasoconstriction.

-Such substances would not accumulate in UUO because they would be excreted by the contralateral kidney. E.g. Atrial natriuretic peptide (ANP)

In summary, • both UUO and BUO involve increases in renal vascular resistances

and increases in ureteral pressures. the timing and regulation of these changes differ• With UUO, early renal vasodilation primarily mediated by

prostaglandins and NO is followed by prolonged vasoconstriction and normalization of intratubular-ureteral pressure as the contralateral kidney contributes to fluid balance.

• With BUO, little early vasodilation is seen, and vasoconstriction is more profound. When the obstruction is released, the postobstructive diuresis is much greater with BUO because volume expansion, urea and other osmolytes, and secreted ANP contribute to a profound diuresis and natriuresis.

Partial Ureteral Occlusion• Formation of glomeruli and tubules may be

compromised so that irreversible changes occur without total loss of kidney function.

• Partial neonatal obstruction can impair nephrogenesis independently of renal functional decline

• these changes may depend upon : -species-stage of renal development-degree of occlusion.

Egress of Urine from the Kidney

• urine may still egress from the kidney. • extravasation at the calyceal fornix

(pyelosinus) that occurs with acute obstruction, typically ureteral stones.

• Extravasation of urine into the venous (pyelovenous) and lymphatic system (pyelolymphatic)

• In chronic obstruction, fluid is thought to exit into the renal venous system.

Effects of Obstruction on Tubular Function

• Postobstructive diuresis:- Commonly after reversal of BUO - uncommonly after release of UUO probably as a consequence of the contralateral renal unit’s functional capacities that are enhanced by an upregulation of ion transporters

Urinary Concentrating Ability

• Normal urine concentrating ability requires:- Hypertonic medullary interstitial gradient because of active salt reabsorption from the thick ascending limb of Henle. - Urea back flux from the inner medullary collecting duct - Water permeability of the collecting duct mediated by vasopressin and aquaporin water channels.

• Obstructive nephropathy can disrupt some or all of these mechanisms.

• Thus dysregulation of aquaporin water channels contribute to the long-term polyuria and impaired concentrating capacity

• These defects are enduring and correct slowly with time.

Sodium Transport

• Although ANP appears to play a role in sodium diuresis after release of BUO, it is unlikely to affect sodium transport defects associated with UUO.

• Sodium excretion is greater after relief of BUO because extracellular volume is expanded and ANP directly affects transport and glomerular filtration.

• The sodium transport defects associated with UUO is most likely due to selective cell membrane changes in the nephron that reduce the number and effectiveness of sodium transporters. Such changes may also occur with BUO.

• Ischemia can also be a mediator of reduced transporter expression. • changes in renal interstitial pressure and local generation of

natriuretic substances. • Thus substrate delivery may be a regulatory step in the expression

of sodium and possibly other transporters.• Intrarenal and extrarenal substances and hormones can also

modulate sodium transport. E.g. PGE2 in the renal medulla• The FENa following relief of BUO is typically greater than that

after UUO because BUO causes retention of Na, water, urea nitrogen, and other osmolar substances and increased production of ANP, all of which stimulate a profound natriuresis.

Potassium Transport• Potassium and phosphate excretions follow changes in sodium;

they are decreased with UUO because of altered transporters and postobstructive retention and increased transiently with BUO in parallel with the massive natriuresis.

• there is a decrease in K+ excretion, with the relief of UUO.-due to reduced delivery of Na+ to the distal nephron -low volume flow rate that would minimize the transmembrane gradient for K+ secretion. -an intrinsic defect in K+ secretion

• K+ excretion increases , with the relief of BUO. -due to the massive increases in Na+ and water delivery to the collecting duct acting as stimuli to secretion - also to the presence of high levels of ANP that can stimulate K+ secretion in the distal nephron

Hydrogen Ion Transport and Urinary Acidification

• Obstruction causes a deficit in urinary acidification that has been demonstrated in human subjects as well as animal models.

• A number of causes for the lack of acidification, including:- defects in H+-ATPase or H+- K+-ATPase- Cl−/HCO3− exchange- Back leak of protons into the renal interstitium- Failure to generate a satisfactory transluminal electrical gradient.

Effects of Obstruction on Anion and Other Cation Transport

• The effects on phosphate reabsorption after the release of obstruction vary depending upon whether it was bilateral or unilateral.

• When BUO is released, accumulated phosphate is rapidly excreted in proportion to sodium

• Conversely, a decrease in phosphate excretion and a net retention occur with release of UUO.

• Magnesium excretion is markedly increased after the release of either UUO or BUO.

• calcium excretion may be increased or decreased, depending to a degree on the type of obstruction and the species.

Effect of Obstruction on the Excretion of Peptides and Proteins

• Changes in peptide excretion reflect mediators and markers of renal damage.

• Monocyte chemoattractant protein 1- Its excretion in the urine after UUO increases - an index of tubular damage.

• - Epidermal growth factor (EGF) excretion- The renal cortical and outer medullary concentration of pre-pro-EGF- The excretion of Tamm-Horsfall protein All decrease with obstruction.

• Urinary enzymes derived from the proximal tubule, e.g. alkaline phosphatase, γ-glutamyltransferase, N-acetyl-β-D-glucosaminidase, and leucine aminopeptidase - elevated in patients with obstructed kidneys

Metabolic Determinants of Ion Transport

• Renal obstruction provokes a number of changes in the metabolic cascade.

• There is a shift from oxidative metabolism to anaerobic respiration.

• This shift results in a reduction of renal ATP levels, an increase in amounts of adenosine diphosphate (ADP) and adenosine mono- phosphate (AMP), and an increase in the renal lactate- to-pyruvate ratio

Cellular and Molecular Mechanisms Leading to Tubular Cell Death through

Apoptosis

• Renal obstruction tubular atrophy and cell death.

• Apoptosis triggered by both intrinsic and extrinsic factors degradation and condensation of the nucleus cells further degrades into apoptotic bodies phagocytized by healthy cells

• Glomerular cells appear to be resistant to obstruction-induced apoptosis.

• Caspases mediate apoptotic cell death in obstructed kidneys

• Two distinct pathways of caspase1- activation of membrane death receptors by extrinsic

binding of tumor necrosis factor alpha (TNF-α) to its receptor.

2- involves intrinsic stress signals that result in mitochondrial release of proapoptotic proteins such as cytochrome c.

• The two pathways activate effector caspases cleave nuclear and cytoplasmic components condensation of nuclear material cell death.

• Angiotensin blockade or ACE inhibition has been shown by some investigators to reduce apoptosis in the early phases of renal obstruction

• TNF-α can be a directly cytotoxic cytokine that can induce apoptosis in addition to its role in renal inflammation.

Cellular and Molecular Changes Leading to Fibrosis

• Urinary tract obstruction leads to progressive and, eventually, permanent changes in the structure of the kidney, including:-tubulointerstitial fibrosis-tubular atrophy and apoptosis-interstitial inflammation.

• In other words:Ureteral obstruction leads to renal inflammation, increased extracellular matrix formation, tubulointerstitial fibrosis, and apoptosis of renal tubule cells.

• Although the events leading to fibrosis are thought to be initiated by increased angiotensin II, other profibrotic factors appear to play a significant role because inhibition of angiotensin synthesis by ACE inhibitors or antagonism of the AT1 receptors blunts but does not completely abolish the fibrotic process

Experimental Treatment Approaches to Attenuate Renal Fibrosis and

Functional Impairment

• These studies suggest an important role of angiotensin-mediated profibrotic and apoptotic events occurring with renal obstruction that can be reduced with currently available inhibitors of angiotensin synthesis or receptor blockade.

Compensatory Renal Growth• An increase in contralateral renal volume has been detected

ultrasonographically when contralateral hydronephrosis or unilateral renal agenesis is present.

• influenced by several factors including:-age-degree of obstruction-duration of obstruction.

• Both hyperplastic and hypertrophic CRG• Studies of humans subjected to nephrectomy, a functional

surrogate for obstruction, have demonstrated that a reduction in CRG occurs with increasing age

• less prominent with partial than with total UUO• While the kidney enlarges -an increase in the number of nephrons

or glomeruli does not occur.

• Insulin-like growth factor I (IGF- I) may play a role.

• Other growth factors, cytokines, and enzymes may be involved in regulating CRG, including IGF binding protein–3 (IGFBP-3), vascular endothelial growth factor (VEGF), matrix metalloproteinase–9 (MMP-9), interleukin-10 (IL-10), and TGF-β

• CRG may be influenced by mitochondrial respiration

Renal Recovery after Obstruction

• When acute, complete ureteral obstruction is promptly relieved, full recovery of global GFR can occur.

• Longer periods of complete ureteral obstruction are associated with diminished return of GFR.

• Histopathological findings may predict recovery of renal function.

• Renal parenchymal thickness based on computed tomography (CT) Further studies are needed to corroborate these results before this approach is used in clinical practice.

• Other factors influence functional returnFactors that have a positive influence on functional recovery include:

- a smaller degree of obstruction- greater compliance of the collecting system- presence of pyelolymphatic backflow

Predictors of diminished recovery of renal function -older age-decreased renal cortical thickness

• Nuclear renography - is the best predictor.• For example:

dimercaptosuccinic acid (DMSA), a cortical agent, has been shown to be superior to tubular selective agents, such as diethylenetriaminepentaacetic acid (DTPA) or mercaptoacetyltriglycine (MAG3), for the prediction of renal recovery

PATHOLOGIC CHANGES OF OBSTRUCTION

• These may be affected by:-the presence of infection-duration of obstruction-intra versus extrarenal localization of the renal

pelvis.

Gross Pathologic Findings• at 42 hours after obstruction :

Dilation of the pelvis and ureter blunting of the papillary tips the weight of this renal unit heavier.

• at 7 days. Pelviureteric dilationweight further increased parenchyma became edematous

• at 12 days The cortex remained slightly enlarged increased calyceal dilatation

• at 21 and 28 daysthe external renal dimensions of both kidneys were similar. the cortex and medullary tissue diffusely thinned.

• At 6 weeksThe totally obstructed kidneys enlarged, had a cystic appearance, and weighed less than the contralateral renal unit The partially obstructed kidneys no gross differences in appearance

Microscopic Pathologic Findings• Widespread glomerular collapse and tubular

atrophy, interstitial fibrosis, and proliferation of connective tissue in the collecting system were reported at 5 to 6 weeks after obstruction

• This is believed to be a result of interplay of several cellular and molecular mechanisms that collectively lead to the subtle development of tubular atrophy, macrophage infiltration/proliferation in the renal interstitial tissue, interstitial fibrosis and progressive loss of nephrons

Electron Microscopic Pathologic Findings

• Including:-tubular atrophy-glomerular collapse-renal pelvic smooth muscle atrophy at 5 to 6 weeks after obstruction

• other changes including:-a cell-poor stroma composed of elastic and collagen fibers in the renal interstitium-obstructed portions of the collecting system.

GENERAL ISSUES IN MANAGEMENT OF PATIENTS

• Diagnostic Imaging- Ultrasonography- excretory urography (EXU)- retrograde pyelography- antegrade pyelography- isotopic renograph - computed tomography (helical)- magnetic resonance imaging- pressure flow study (Whitaker test).

Ultrasonography

• Although it is primarily an anatomic study, Doppler modifications may add a functional component.

- A prospective study of ultrasonography in obstruction revealed a 35% false-negative rate in acute obstruction, underscoring the need to correlate the clinical picture carefully with the radiologic findings.

• Doppler ultrasonography allows measurement of the renal resistive index (RI), which has been used to assess for obstruction. The RI is defined as peak systolic velocity (PSV) minus the end-diastolic velocity (EDV) divided by the PSV.

• values greater than 0.7 reflecting elevated resistance to blood flow and thus suggesting obstructive uropathy.

• Although the presence of hydronephrosis associated with an abnormally elevated RI may be indicative of the severity of obstruction

Excretory Urography• the “gold standard” for the evaluation of the upper urinary

tract

• Advantages:it provides both anatomic and functional information:

• Disadvantages:- the utility of EXU is limited in those with renal

insufficiency. - risk of contrast nephropathy increases with increasing

serum creatinine. - Radiation exposure limits its utility in pregnancy

Retrograde Pyelography• Defines ureteral and collecting system anatomy• considered in:

- renal insufficiency - risks for receiving intravenous iodinated contrast material- anatomy is not sufficiently defined with other imaging studies.

• Loopogram:- another form of retrograde pyelography - evaluating patients with cutaneous urinary diversion when obstruction is suspected.

Antegrade Pyelography

• Helpful- when other imaging studies do not adequately define collecting system or ureteral anatomy- when retrograde pyelography is not technically feasible.

Whitaker Test (pressure flow study)

• First described by Whitaker in 1973• Measurement of renal pelvic pressure during infusion of either

saline or contrast material into the collecting system through a percutaneous needle or nephrostomy at a fixed rate of 10 mL/min.

• A catheter is placed in the bladder to monitor intravesical pressure• subtracted from the measured collecting system pressures to

calculate the “true pressure” within the pelvis.• -A true intrapelvic pressure of less than 15 cm H2O is considered

normal- greater than 22 cm H2O indicative of obstruction- between 15 and 22 cm H2O indeterminate.

• The noted discordant results and the invasiveness of the study limited its applicability in clinical practice.

Nuclear Renography

• noninvasive test • It provides a functional assessment • without exposure to iodinated contrast

material.• The glomerular agent technetium (Tc) 99m

DTPA and The tubular agent 99mTc-MAG3 are most commonly used in the evaluation of obstruction.

• Obstruction can be assessed by measuring the clearance curves, either:from a visual assessment of the pattern or from calculation of the half-time (time at which 50% of the radiopharmaceutical is eliminated from the collecting system).-a half-time less than 10 minutes is considered normal-greater than 20 minutes is considered obstructed-between 10 and 20 minutes is equivocal

• The diuretic renogram is a modification, distinguish truly obstructed collecting systems from those that are dilated but unobstructed.

• In diuretic renography, the diuretic, typically furosemide (F)

• although an F+20 study is reliable when obstruction is demonstrated, both the F−15 and F+0 sequences can induce obstructed patterns in previously equivocal cases

• With the emergence of such techniques in isotopic renography, the differential renal function and drainage can be estimated with greater precision

Computed Tomography and Magnetic Resonance Imaging

• Both CT and MRU provide superior imaging of the obstructed upper urinary tract as compared to EXU

• Other advantages include its speed, reproducibility, and ability to detect other pathologic entities

• Noncontrast CT directly demonstrates calculi classically considered radiolucent when evaluated by plain radiography, including uric acid, xanthine, dihydroxyadenine, and many drug-induced stones. Exceptions, however, are calculi composed of protease inhibitors, which are not visualized by noncontrast CT.

• both MRU and CT have critical roles in evaluating select patients with urinary tract obstruction.

• Although these studies can estimate renal function nuclear renography remains the current gold standard.

Hypertension• A well-recognized sequela of BUO or obstruction

of a solitary kidney. • Hypertension is significantly less common,

however, with UUO• UUO the contralateral, unobstructed kidney

compensates and eliminates excess volume and solutes.

• In summary, there is a good chance of reversal of new-onset hypertension with relief of BUO, but this is less likely with UUO.

Renal Drainage• immediate drainage of the affected renal unit(s) in case of Ureteral

obstruction that is- symptomatic- accompanied by fever- complicated by an undrained infection- high grade- bilateral- inducing renal failure

• may allow temporary drainage until a definitive procedure is performed

• may be a permanent form of management. • urinalysis and culture• Antibiotic therapy• The choice of drainage ultimately depends on the clinical setting.

indwelling ureteral stents and percutaneous nephrostomy tubes

• Ureteral stenting may not be as effective for treating patients with extrinsic ureteral obstruction.

• A diagnosis of cancer, metastatic disease requiring chemotherapy or radiation, and renal insufficiency were predictors of stent failure in this series.

• Closer monitoring for stent failure should thus be considered in patients with extrinsic ureteral obstruction

• risk factors for stent failure:- higher serum creatinine value-The presence of extrinsic ureteral obstruction due to bladder or prostatic pathology, especially advanced malignancies -Encrustation: pregnant patients, due to increased calcium excretion during pregnancy urinary tract infection (UTI)stasisdehydrationrenal insufficiencyprolonged dwell timehistory of nephrolithiasis

Choice of Surgical Intervention

• Definitive management is based upon:- cause of the obstruction-functional recovery of the affected kidney-condition of its counterpart-patient’s age-medical status.

• Endoscopic, open, or laparoscopic ablative and reconstructive procedures may all be used.

• The decision to remove a kidney should be made only after the affected kidney has been adequately drained for a sufficient period of time, 6 to 8 weeks

Pain Management

• Five classes of drugs are used to treat pain associated with acute renal colic:- nonsteroidal anti-inflammatory drugs (NSAIDs)- narcotic analgesics- calcium channel blockers- corticosteroids- α1 blockers

• The present level of evidence supports the role of NSAIDs as first-line drugs for the management of renal colic presenting to the emergency department, with narcotics being reserved as second-line drugs.

• The choice of pain management should be based on the patient’s clinical profile.

• NSAIDs should not be used in patients with renal insufficiency, because this could be exacerbated by the induced reduction in RBF.

• COX-1 inhibitors should not be administered to patients at risk for gastrointestinal bleeding or when optimal platelet function is needed.

• the market withdrawal of some COX-2 inhibitors, related to increased risk of cardiac morbidity, underscores the need for prospective trials to assess their long-term safety in managing patients with renal colic.

• Patients may be fluid depleted as a result of anorexia and emesis, and therefore should receive intravenous hydration.

• there is no evidence that intravenous hydration facilitates stone passage

Post obstructive Diuresis• Mechanisms• Following the relief of urinary tract obstruction, post-

obstructive diuresis—a period of significant polyuria— may ensue.

• Urine outputs of 200 mL/hr or greater may be encountered.

• Postobstructive diuresis occurs primarily with BUO and is usually self-limiting.

• mainly after relief of BUO or obstruction of a solitary kidney • rarely occur when there is a normal, contralateral kidney

• a “pathologic” postobstructive diuresis may ensue, characterized by: inappropriate renal handling of water or solutes, or both.

• It is due to a number of mechanisms, including:- a derangement of the medullary solute gradient

- a number of altered signaling and transport pathways.

• Downregulation of sodium transporters • The increased ANP induce a saline diuresis • other natriuretic peptides, such as the

Dendroaspis natriuretic peptide, may play a role. • poor responsiveness of the collecting duct to

antidiuretic hormone (ADH). due to a downregulation of aquaporin water channels in this segment of the nephron and perhaps in the proximal tubule

Clinical Management of Postobstructive Diuresis

• The majority of patients do not demonstrate a clinically significant postobstructive diuresis following relief of urinary tract obstruction.

• Those who are susceptible to this phenomenon typically have signs of fluid overload:-edema-congestive heart failure-hypertension

• A catheter should be placed to drain the bladder rapidly in those with urinary retention.

• should be monitored for a postobstructive diuresis. -Serum electrolytes-magnesium-blood urea nitrogen (BUN)-creatinine

• monitoring depends on:-presence of risk factors for postobstructive diuresis-mental status-renal function-electrolyte status.

• Those with normal renal function and electrolytes, no evidence of fluid overload, and who are mentally alert - should have their vital signs and urine output monitored. - They are allowed free access to oral fluids, - and if they do not manifest signs of a postobstructive diuresis they can be discharged and return later for further urologic evaluation and care.

• If they show signs of a postobstructive diuresis but are alert, able to consume fluids, and have normal vital signs. - observation is continued and the patients may consume fluids as desired.

• If patients have signs of fluid overload, azotemia, or poor cognitive function, or if hypotension or other indicators of hypovolemia develop-more intense monitoring should be instituted. -Vital signs - urine output are checked more frequently. - Electrolytes, BUN, magnesium, and creatinine are assessed every 12 hours, and more frequently if necessary. - Urinary osmolarity should be checked in this setting.

• The clinically stable patient with good cognitive function -free access to oral fluids. -Intravenous fluids should probably not be administered, because this may prolong the period of diuresis. However, there may be a theoretical role for maintenance of volume expansion in this setting

• Those with poor cognitive function • should receive intravenous hydration, but below the

normal maintenance amounts. • The majority have a self-limiting physiologic diuresis.

On rare occasions, a pathologic diuresis develops and the patients can become hypovolemic because of excess water loss.

• These patients warrant the most intense monitoring and require careful electrolyte and fluid replacement, initially by an intravenous route.

• The urine is usually isosthenuric initially and intravenous fluid replacement with 0.45% saline administration at a rate lower than the urine output is recommended

SELECTED EXTRINSIC CAUSES OF URETERAL OBSTRUCTION

Retroperitoneal Fibrosis• uncommon • a fibrotic and inflammatory mass envelops

and potentially obstructs retroperitoneal structures including either or both ureters.

• Grossly, retroperitoneal fibrosis appears as:a fibrous, whitish plaque that encases -the aorta,-inferior vena cava, -their major branches, -the ureters, -other retroperitoneal structures-intra- peritoneal structures including the gastrointestinal tract.

• Its longitudinal axis extends from the renal hilum to the pelvic brimmay extend into the pelvis, mediastinum, and even the optic orbit.

• The etiology - not well characterized. • A number of mechanisms have been proposed. - the development of vasculitis in the adventitial

vessels of the aorta and perioaortic small vessels. - Other immunologic events may play a role. - The presence of clonal and oligoclonal B cells

suggest that an errant B-cell disorder may play a role.

- Environmental toxins may play a role

• Epidemiology:• It is more common in males, with a 2 to 3 : 1

male-to-female ratio. • The mean age at onset is typically 50 to 60 years, • it may manifest in children as well as the elderly • Genetic influence is not thought to play a major

role• Retroperitoneal fibrosis is associated with HLA-

DRB1*03, an allele linked to a number of autoimmune diseases.

• Numerous medications have been associated with the development of retroperitoneal fibrosis

• An underlying malignancy should always be considered, because one is reported to be present in 8% to 10% of such cases

• Unique infections such as tuberculosis, histoplasmosis, and actinomycosis.- It can occur after abdominal or pelvic surgery as well as abdominal trauma.

• Radiation and systemic chemotherapy .• systemic diseases including autoimmune and

inflammatory processes.

• Symptoms:back, abdominal, or flank pain, weight loss, anorexia, and malaise.

• Signs: hypertension (in 50%), fever, and lower extremity edema. signs or symptoms attributable to ureteral or vascular obstruction

• laboratory abnormalities:- elevations in acute phase reactants e.g. ESR and CRP- elevated serum creatinine- hypergammaglobulinemia- normochromic, normocytic anemia.- Tests for autoimmune diseases may also be positive

• The classic radiologic findings:-medial deviation of extrinsically compressed ureters -hydronephrosis. - smooth, well- demarcated, hypoechoic or isoechoic mass anterior to the lumbar or sacral spine

• Retrograde pyelography demonstrates hydronephrosis, with medially deviated and segmentally narrowed ureters without filling defects

• CT or MRI- CT typically reveals a well- demarcated retroperitoneal mass,

isodense with muscle on unenhanced studies- MRI allows superior soft tissue discrimination and can more

accurately distinguish the plaque from the great vessels than unenhanced CT.

• If there is evidence of obstructive uropathy at presentation, therapy should be first directed at its correction. -internalized ureteral stents-percutaneous nephrostomy

• Biopsy to exclude malignancy should be performed next. This can be attempted percutaneously with CT, MRI, or ultrasound guidance.

• The potential morbidity of ureterolysis, accurate image-guided biopsy techniques, and more sensitive cross-sectional imaging studies for diagnosis and follow-up have made medical therapy the preferred approach in this setting.

• no randomized prospective studies addressing the merits of initial medical therapy versus a surgical approach.

• Medical therapy has been directed to address the presumed autoimmune and inflammatory components of retroperitoneal fibrosis.

• corticosteroids• Tamoxifen, a nonsteroidal antiestrogen

• Ureterolysis is undertaken if medical therapy fails or if the patient is not a candidate for medical therapy.

• Bilateral ureterolysis is recommended - progresses to involve the contralateral side.

• The ureteral dissection - care to avoid devascularization of the ureter.

• A biopsy should be repeated - sampling error associated with percutaneous biopsy.

• Several strategies have been employed to prevent recurrent ureteral involvement in the fibrotic process:- The ureter may be displaced to a lateral position - brought to an intraperitoneal location by closing the peritoneum behind it, or wrapped within a sleeve of omentum.

• No single method has been definitively demonstrated to generate superior results

• alternatives include:ileal ureter replacementautotransplantationchronic ureteral stentingnephrostomy tube drainage.

• Ureteral stents can generally be removed 6 to 8 weeks after ureterolysis

• Long-term follow-up in those subjected to medical or surgical therapy is warranted.

• Serial cross-sectional imaging to assess recurrence, progression, malignancy.

• Renal function monitored.

Pelvic Lipomatosis• Rare

benign conditionmarked by exuberant pelvic overgrowth of nonmalignant but infiltrative adipose tissue, usually in the abdominal and pelvic cavities.

• Occur in perivesical and perirectal spaces• The etiology and incidence are unknown. • Obesity play a role • radiographic improvement and worsening in

response to weight loss and gain, respectively.

• Possible genetic etiology :- An abnormality in the chromatin-regulating high-mobility group A (HMGA) proteins has been implicated- genetic mutations have been traced to the HMGA2 gene located on the hypermobile cluster on chromosome 12

• chronic inflammatory response triggered by urinary tract infection.

• Presentation: - one half of patients present with lower urinary tract symptoms - one quarter with bowel symptoms, typically constipation.- Suprapubic, back, flank, or perineal discomfort

• Physical findings:- a suprapubic mass- a high-riding prostate- indistinct pelvic mass. - Hypertension

• Radiologic signs:- On plain film, increased pelvic lucency - On excretory urography, the bladder characteristically assumes a pear or gourd shape, extrinsically compressed and elongated, and the bladder base is frequently elevated

• leads to severe bilateral hydronephrosis. • causes significant displacement of the distal

ureters medially• Hydroureteronephrosis • CT demonstrates

-pelvic fat -Extrinsic compression of the rectum -differentiating pelvic lipomatosis from other

• MRI - permits characterization of fat deposits

• Evaluation should include cystoscopy- because some form of proliferative cystitis has been found in 75% of patients, including cystitis glandularis in up to 40% However, the majority of patients with cystitis glandularis do not have pelvic lipomatosis.

• cystitis glandularis due to accumulation of perivesical fatcausing compression of the bladder that leads to venous stasis, and the development of an edematous urothelium that subsequently sloughs off. As the urothelium regeneratesundergo a metaplastic change leading to development of cystitis glandularis.

• Continued cystoscopic surveillance is recommended - risk of bladder adenocarcinomaElongation of the prostatic urethra, elevation of the bladder neck, and pelvic fixation may impair cystoscopic access to the bladder.

• flexible cystoscopy may be required if anatomic distortion precludes rigid cystoscopy.

• The clinical signs and symptoms:lower urinary tract symptomshematuriapassage of debris in the urineproblems with defecation.

• there is agreement that in light of the potential for progressive ureteral obstruction, long-term follow-up is mandated.

• steroids, chemotherapy, radiotherapy, and chronic antibiotic therapy have not been reported to be successful.

• Surgical options include:ureteral stentingpercutaneous nephrostomyureteral reimplantationurinary diversion with or without cystoprostatectomy.

• Pelvic exploration – cautiously due to obliteration of normal anatomic planes and increased vascularity within the fatty mass.

Obstetric and Gynecologic

Pregnancy• Hydronephrosis develops commonly during

pregnancy• occurrence varying between 43% and 100%.• Approximately one third of patients may

have persistent hydronephrosis during the first postpartum week, but it resolves in the majority within 6 weeks

• Two etiologies for hydronephrosis of pregnancy:- hormonal - mechanical.

• nonmechanical mechanism.Progesterone promote ureteral dilatation and subsequent development of hydronephrosis

• mechanical etiologyafter the 20th week of gestation, a time when the uterus is large enough to compress the ureters extrinsically

• Ultrasonographic finding: hydroureteronephrosis extending to the pelvic brim.

• Magnetic resonance urography has been advocated by some as a noninvasive, nonradiating method of assessing those with hydronephrosis of pregnancy. The presence of hydroureter below the pelvic brim is readily apparent on high-resolution T2 sequences, and filling defects representing stones or soft tissue may be seen

• Mx:• conservative measures:

- intravenous hydration- analgesics- antibiotic therapy

• placement of ureteral stents may be necessary - Rapid stent encrustation may be problematic, as urinary calcium excretion increases during pregnancy- necessitate more frequent stent changes.

• Percutaneous nephrostomy is an alternative

Benign Pelvic AbnormalitiesTubo-ovarian Abscess.• Tubo-ovarian abscess, occurring in approximately 15% of those afflicted with

PID, may cause extrinsic ureteral obstruction, lead to anuria• Ureteral obstruction may resolve with:

- antibiotic therapy - transvaginal drainage of the abscess. - open surgical or laparoscopic intervention - Placement of an internalized ureteral stent or percutaneous nephrostomy

Endometriosis. • Defined as the presence of functional endometrial tissue

in an ectopic site. • potential for malignant transformation • 10% to 20% of women of reproductive age• peak incidence in the mid-20s

• Genitourinary endometriosis is a rare condition • involvement of the urinary tract in 1% to 5% of

those afflicted with this disorder.• - found in the bladder, accounting for 70% to

80%. - The ureter may be involved in 15% to 20% - Rarely, renal and urethral involvement

• may be either intrinsic or extrinsic.

• -Eighty percent of ureteral endometriosis is extrinsic

• One theory for ureteral involvement:is the occurrence of retrograde menstruation and implantation of endometrial cells.

• Vesical endometriosis- solitary - involves the dome of the bladder.

• Notably, a significant portion of patients with ureteral endometriosis do not have genitourinary symptoms.

• Because a large percentage of patients with ureteral endometriosis can have asymptomatic obstruction of the kidney with a loss of renal function, it has been recommended to image the upper urinary tract in all patients with pelvic endometriosis.

• Treatment goals: (1) preservation of renal function, with long-term relief of urinary obstruction, (2) management of the ongoing disease process by completely excising or ablating the endometriotic tissue with its reactive fibrotic component, (3) maintenance of the patient’s fertility(4) relief of the patient’s symptoms with the least invasive methods available.

• If renal function is normal and there is minimal to mild hydronephrosis with no functional obstruction as determined by radionuclide renal scanning, hormone therapy may be prescribed.

• Ovarian hormonal ablation with gonadotropin-releasing hormone agonists

• Postmenopausal patients controlled withluteinizing hormone–releasing hormone (LHRH) analogues.

• Surgical intervention:

• total abdominal hysterectomy and bilateral salpingo-oophorectomy.- If not desire future pregnancy

• lesser extirpative procedures, such as unilateral oophorectomy. - If pregnancy is desired

• Ureterolysis – ureteral obstruction with extrinsic disease. If laparoscopic ureterolysis - Success rates of 85%

• ureteroscopic resection or ablation- If intraluminal ureteral • distal ureterectomy with reimplantation. by an open surgical, laparoscopic

or robotic-assisted approach.- if unsuccessful or extensive disease

• Surveillance with sonography is advisable to detect recurrent ureteral obstruction in patients with ureteral endometriosis treated by hormones, endourological ablation, or surgical extirpation

Ovarian Remnants• from residual, viable ovarian tissue after bilateral

salpingo-oophorectomy. • complication of a technically difficult oophorectomy• Mass effect or a localized fibrosis may cause extrinsic

ureteral obstruction.• Treatment:

surgical excision of the mass and ureterolysis. • Preoperative ureteral stenting • Medical management

leuprolide acetate therapy - chronic medical therapy to prevent recurrence

Mass Lesions of the Uterus and Ovaries. • include uterine fibroids, ovarian cysts, and

ovarian fibromas. • Uterine fibroids, the most common tumor of the

upper female genital tract, are also the most common, benign gynecologic neoplasm causing ureteral obstruction

• The most common site of extrinsic ureteral obstruction at the level of the pelvic brim.

• Surgical resection or ablation of the leiomyomas

Vascular Causes of Ureteral Obstruction

Arterial Causes of ObstructionAbdominal Aortic Aneurysm. • Clinical signs and symptoms of ureteral obstruction may be the initial

manifestation of an abdominal aortic aneurysm (AAA)• due to a mass effect or localized inflammation • CT scanning • Ureteral findings vary.

- pushed laterally on both sides- one side may deviate laterally while the opposite side is drawn medially within the perianeurysmal inflammation- both may be medially deviated.

• lateral deviation of the ureter with AAA - not associated with obstruction• The medial deviation of the ureter associated with the desmoplastic reaction of

inflammatory aneurysms (IAAA), however, carries a more significant risk of ureteral obstruction. Placement of internalized ureteral stents

• open surgery or an endovascular approach warrant close monitoring for recurrent or de novo ureteral obstruction

Arterial Causes of ObstructionIliac Artery Aneurysms. • can cause ureteral obstruction, which may even lead to renal failure• 35% of those with common iliac artery aneurysms • 19% of those involving the internal iliac artery. • if a pulsatile mass is palpated on rectal examination. • ultrasonography, MRI, and CT. • extrinsic compression or localized inflammation • Treatment options for obstructing common iliac artery aneurysm include:

-ureterolysis -aneurysm resection and graft placement -endovascular graft placement.

• Options for obstructing internal iliac artery aneurysms include:-open surgical ligation-ureterolysis-initial endovascular occlusion and subsequent retrograde placement of an iliac artery endovascular graft.

Arterial Causes of Obstruction

• Internalized ureteral stents are typically placed before these procedures and are removed 6 to 8 weeks later.

• observed closely - ureteral obstruction resolves or recurs.

• If it recurs, management options include:-chronic internalized ureteral stenting-ureterolysis,-ureteral reconstruction

Arterial Causes of Obstruction• An additional cause is the retroiliac ureter • Treatment :

- transection of the ureter and transposition to the normal, anterior position.

• Other genitourinary abnormalities are associated with this condition, including renal hypoplasiavesicoureteral refluxureteral ectopia,ectopic vas deferenshypospadiasbifid scrotumhypoplastic or duplex uterushydrometrocolpos.

• Therefore a search for other genitourinary abnormalities should be undertaken in patients with retroiliac ureter.

Arterial Causes of ObstructionUreteral Obstruction after Vascular Graft Placement. • Hydronephrosis occur 10% to 20% after aortic bypass graft surgery. • several possible causes

- Mechanical obstruction of the ureter due to graft placement anterior to the ureter- ureteral entrapment in perigraft fibrosis- ureteral devascularization- unidentified ureteral ligation- ureteral compression from a postoperative pseudoaneurysm .

• Symptoms and signs :- arise in the first postoperative year - flank pain- anorexia- hypertension- anuria- renal failure or insufficiency. - asymptomatic

Arterial Causes of Obstruction• Management of this problem varies. • If hydronephrosis early in the postoperative and renal function is not

compromised: - close observation - Temporary internalized ureteral stent or percutaneous nephrostomy drainage

• If not resolve spontaneously and the graft is placed anteriorly- transposition of the ureter - vascular graft

• To reduce the risk of graft infection- vascular graft transected and repositioned

• if persistent ureteral obstruction to perigraft fibrosis.- steroid or tamoxifen therapy- careful follow-up is mandatory - because delayed treatment failure.

• if the former is not feasible or if medical therapy is not successful. - Ureterolysis, and ileal ureter substitution

• Chronic ureteral stenting - not candidates

Arterial Causes of Obstruction

Uterine Artery Aneurysms/Pseudoaneurysms (UAA).

• associated with pregnancy. • Symptomatic ureteral obstruction leading to

hydronephrosis • Managed:

-radiographic embolization-surgical ligation.

Venous Causes of ObstructionPuerperal Ovarian Vein Thrombophlebitis• a mechanical effect from a dilated ovarian vein• “ovarian vein syndrome.” • Puerperal ovarian vein thrombophlebitis• postpartum condition - cause ureteral obstruction -due to perivenous phlegmon formation and

resultant periureteritis • more common on the right• may occur in either or both ovarian veins. • signs and symptoms:

-nonspecificu sually beginning 2 to 3 days after birth. -abdominal or flank pain and fever

• On physical examination:- abdominal tenderness and guarding - A tender indurated adnexal mass may be discerned in 50% of patients

• - The majority of patients respond to conservative measures, including antibiotic therapy- Internalized ureteral stent placement - Laparoscopic or open surgical ureterolysis - ovarian vein resection

Venous Causes of Obstruction

Testicular Vein Thrombophlebitis.• Thrombophlebitis of the left testicular vein • causing extrinsic obstruction of the left ureter • surgical exploration revealed

a dilated and thrombosed left testicular vein impinging upon the proximal ureter.

• Ureterolysis and excision of the thrombosed vein eradicated the obstruction.

• Also occur on the right side

Venous Causes of ObstructionCircumcaval Ureter. • an anomalous course posterior, medial, anterior, and finally lateral to the

inferior vena cava (IVC) may lead to extrinsic obstruction of the ureter. • incidence of circumcaval ureter is approximately 1 in 1100. • 2.8-fold male predominance• Symptomatic patients - in the third or fourth decade of life• This vascular anomaly is not always associated with ureteral obstruction • The majority involve the right ureter• although left-sided circumcaval ureter has been reported in association

with a duplicated IVC and in association with situs inversus • Other genitourinary anomalies may be present.• Circumcaval right ureter with a retrocaval horse-shoe isthmus

Venous Causes of Obstruction• Circumcaval ureter classified using different parameters

based on intravenous urography or retrograde pyelographic findings.

• Bateson and Atkinson (1969) classified a ureter with an S-shapedfish hookshepherd’s crook appearance as type I

• A less-angulated “sickle-shaped” ureteral deformity is classified as type II

• The point of maximal obstruction in type I is lateral to the lateral margin of the IVC and is associated with a greater degree of hydronephrosis thantype II, in which the point of obstruction is at the lateral border of the IVC

Venous Causes of Obstruction

• Another classification scheme is based on the level of obstruction:- type I crosses at the level of the third lumbar vertebra- type II crosses at the level of the ureteropelvic junction.

• The diagnosis:pyelographic findings confirmed with CT and MRI Diuretic renography

Venous Causes of Obstruction• Treatment is undertaken only in the presence of

obstruction. - The ureter is divided proximally and at the distal point, from which it emerges lateral to the IVC. - A spatulated ureteroureterostomy is performed. by open, laparoscopic, and retroperitoneoscopic approaches and is best dictated by the surgeon’s experience.- pure robotic repair of retrocaval ureter

• The most common complication: ureteral stricture 13%