Obstruction of Urinary Tract

Introduction

Blockage at ureter level (acutely) or distally in bladder or at urethra (most common cause in man is prostatic enlargement)

Site of Obstruction:

in urinary tractÞ enlarged prostrate, urethral stricture; cancer of the kidney; bladder stones, papillary necrosis, clot, tumor; phimosis (foreskin is tight), paraphimosis (foreskin is drawn back)

outside urinary tract Þ ovarian cancer, dilated aortic aneurysm, testicular or lymph node cancer

Diagnosis: Patient History, examination, blood tests, radiologic evaluation

Treatment: depends on gravity of situation; nephrostomy tubes, urinary stents, urinary catheter to alleviate, obstruction, dialysis

Four Main Effects

(1) Acute ß in GFR (information from animal model experiments)

(a) bilateral ureteral obstruction

initially, ureteral smooth muscle contraction Þ ureteral constriciton Þ acute Ý intratubular pressure

relatively rapidly (hours) smooth muscle relaxation Þ ureteral dilatation Þ ß intratubular pressure

GFR/RBF initially Ý (1-4 h) followed by dramatic ß (6-24 h) Þ do not result from the tubular pressure changes!!!

initial Ý (1-4 h) due to arteriolar vasodilation of afferent arteriole; mediators: dilators (PGE₂, NO)

dramatic ß (6-24 h) due to marked arteriolar vasoconstriction of afferent arteriole Þ ß in perfusion pressure

Þ some nephrons not perfused at all (redistribution of blood flow to only a portion of the nephrons) and SNGFR ß in those that are perfused; mediators: constrictors (ANG II, Thromboxane A2, Leukotriene)

Ý TxA₂ Þ Ý MCP-1 (chemoattractant for macrophages and T-cells) Þ cellular changes (fibrosis/atrophy)

Ý ANG II Þ infiltration and Ý TGF beta Þ profibrogenesis (ACE Inhibitor may be a possible treatment)

Acute obstruction leads to macrophage rich infiltrate in the tubulointerstitium within only a few hours

possibly due to chemoattractants released by tubular/interstitial cells
these macrophages (or mesangial cells) could be the possible source of the vasoconstrictive mediators

ß GFR Þ kidney thinks ß volume Þ proximal tubule reabsorbs Na/water/urea (BUN/Cr ratio is very high)

Can begin the initial stages of interstitial fibrosis

Possible Mechanisms of Fibrosis and Atrophy Þ further decrease in GFR

interstitial fibrosis occurs by 7-16 d after initiation of obstruction in animal models and is manifested by Ý in collagen deposition and fibroblasts with an associated mononuclear cell infiltrate

TGF-b is Ý Ý Ý ; Collagen I, III, IV are Ý ; Metallic proteinases are ß ; RNA metallic proteinase inhibitors are Ý :

Produce collagen deposition and ß metalloproteins

induces influx of other cells into the area, resulting in fibrosis

apoptosis appears to participate in tubular atrophy and ß in renal cortex size; unclear which cells induce apoptosis

(b) Prostate obstruction Þ overflow incontinence Þ polyuric; thus polyuric does not rule out obstruction

(c) Unilateral obstruction Þ normally no significant change in GFR unless you start off with an abnormal Cr level (say 4) then once the unilateral obstruction occurs, Cr raises from 4 to 8 and GFR is affected

(2) CRF (chronic renal failure) – wasn’t discussed

(3) Ý K, Metabolic Acidosis (hyperchloremic metabolic acidosis with hyperkalemia) – due to defects in tubular function

NET EFFECT: volume overload with hyperkalemic metatbolic acidosis out of proportion to renal failure

(a) Defects in sodium reabsorption –due to downregulation of specific transporter activity needed for reabs. of Na⁺; can result in inability to retain Na⁺ after obstruction is resolvedÞ post obstructive diuresis(see below)

vol. overloaded (Ý total body Na⁺) when in acute obstructive renal failure (markedly ß GFR, ß Na⁺ excretion)

(b) Defects in urinary concentration/dilution – cannot produce osmolar interstitial gradient (Na⁺not resorbed)

although ADH may be present, it does not function due to a post receptor defect (effectively nephrogenic DI)

leads to excess loss of water after the obstruction is resolved Þ post obstructive diuresis (see below)

(c) Defects in potassium transport – some patients have inappropriately low renin and aldo. Þ unable to excrete K⁺

in some cases there may be damage to Na⁺ or K⁺ channels in the distal tubule resulting in inability to excrete

Hyperkalemia can be a presenting sign

(d) Defects in acid excretion – patients can present with a renal tubular acidosis (non anion gap)

ß cortical collecting tubular H⁺excretion (H⁺ATPase either nonfunctional, fewer present, or wrong distribution)

ß proximal tubular NH3 production

50% of patients with Urinary pH of 5.5 and ß Urinary NH3 Þ indicative of type 4 RTA

Other 50% of patients Þ Urinary pH of 7.5

Give Na⁺ and SulfateÞ if don’t excrete H⁺ and reabsorb Na⁺as expected, but just pee it outÞ typical result for RTA

(4) Post Obstructive Diuresis – rarely, after release of bilateral ureteral obstruction or obstruction of a solitary kidney, significant diuresis takes place due to basic tubule and glomerular defects (see above)

(a) ß reabsorption in the proximal tubule

(b) ß Na⁺ and ß fluid reabsorbed in TAL and DT, so CD does not concentrate

become polyureic Þ excrete a lot urine due to volume overload Þ want to get rid of NaCl in their urine

In small % of patients Þ NaCl wasting Þ nephrogenic diabetes insipidis and/or hypovolemic

ObstructionÞ Hydronephrosis

imbalance between urine formation and resorptionÞ distended, flaccid kidney

fluid exits renal pelvis by extravasation and backflowÞ kidney continues functioning, with collecting system distention

causes:

(1) obstruction (acute or chronic)

(2) structural abnormalities of termination (e.g. vesicoureteral reflux) which may lead to retrograde flow of urine in the urinary tract

(3) functional obstruction due to failure of propulsion of urine from neuromuscluar dysfunction (e.g. neurogenic bladder) – non-obstructive neuropathy