EFFECTS
JOHN
OF OBSTRUCTION
G. ROSE,
ON URETERAL
FUNCTION
M.D.
JAY Y. GILLEN\V,4TEK,
M.D.
Frown the Department of Urology, Universit>Virginia School of Medicine, Charlottesville.
Impairment of Ilrinary flow will lead to significant renal damage, uremia, and death. It is this link hetwern the loss of renal function and obstnlction that has brought about a rather recent interest in the hydrodynamics of the iirinar\ q~stem. Hisk~rically. the urinary tract is cli\ided into an upper arid lower tract, consisting of the collecting system, rt~il pelvis, and ureter, on the OIIV hand, and the bladder and ~ux&ra, on the otller. From the urodynamic viewpoint, this system should he regarded as one physiologic unit that is completely interdependent. Olxtruction at any point along the tract hecause of increased volume and pressure proximally will affect all proximal lmits, alter their normal traILsporting function, and lead to Thus, while this article is nephron damage. concerned with changes that occur in the ureter following obstruction, these same changes apply whethrhr thcb obstrllction is primaril>. in the lipper tract or secondary to a lower tract ol~striiction. The impairment of urine flow within the upper urinary tract may result from either mechanical or fllnctional obstruction. Of the former. fixeign bodies, tumors, inflammatory processes. and congenital and acquired stnlc-
of b’irginia
tural anomalies lead the list; while of‘ the latter. l~laddel (1retero\,esical reflus and nerlrog~~nic are the most common couditiol(s. c~ncountered. In any case, the result is the same: the uppc11 tract does ilot drain satisfktoril;,~, alterations irr Ilreteral structure and function result, and renal filnction is ultimatelv afrec ted. Normal
Peristalsi:,
To gain some insight into the rt’t;Bct of ol)ctruction on transporting fiiuctiol~ \vithin the upper urinary conduit, it is necessq. to discuss normal ureteral function. Trallsporting function within the normal lIpper Ilrinx]c tract is accomplished by both active and passive forces. The active forces result from peristalsis within
5001 LEFT URE:TER
DOG #
--~
Ureteral Pressure mmHg
_
_
-
20 I5 10 ___Jq_ 5
0
__>L’.‘.
8: ~_
during contraciim=4.86
X IO4 dynes/cm2
t 3 MINUTES
POST
URETERAL
TENSION
t IO MINUTES
OCCLUSION
URETERAL
al rest = 3.24 X104 dynes/cm2 during contraction = 4 70 X IO” dyws/cmz
POST
OCCLUSION
TENSION
01 resl = 8.50
X IO4 dynes/cm2
dumq ccmiraclim = 8.34 X 104dyne&m2
intraluminal ureteral pressure, outside ureteral diameter, FIGURE 2. Recording of aortic blood pressure, and respirations in acutely obstructed canine ureter. After ureter is obstructed, baseline intraluminal ureteral pressure is built up behind obstruction, ureteral contractions diminish in face and eventually cease, and ureteral pressure waves also diminish in force and eventually cease.
the calyces, renal pelvis, and ureter, while the passive forces result from the filtration pressure in the kidney. Active peristalsis within the system is dependent upon the contractibility of smooth muscle within the walls of the conduit. As with other muscular organ systems, contractile activity within this system is preceded by an electrical impulse. As the impulse passes distally, a wave of depolarization occurs that induces the smooth muscle to contract causing the conduit to shorten and to oppose its walls. With each contraction, a lo-cm. section of ureter will shorten less than 1 mm.’ The role that this slight decrease in length plays in urine transport is probably minimal. More important is opposition of the conduit walls which results in luminal constriction. The force that acts to bring about opposition of the conduit walls is termed wall tension.’ Tension is a circumferentially directed force which, when increased, will effect luminal constrictions. Several phenomena result from these constrictions that serve to explain the mechanics of active* urine transport. First, urine in the conduit just proximal to constricting segments is formed into boluses. Second, intraluminal pressure within each constricting segment, and therefore behind each bolus, is markedly increased (Fig. 1). The increase in pressure behind each bolus acts to propel the
bolus toward the bladder as contractions pass distally. In this manner, the active transport of urine is accomplished. In addition to these propulsive forces that are dependent upon active peristalsis, urine within the upper urinary conduit is also transported by hydrostatic pressure that is generated through filtration in the kidney. As urine is formed and passes into the collecting ducts, it is transported to the calyces by pressure that is directly related to the glomerular filtration pressure and oncotic pressures. This intratubular hydrostatic pressure may be considered a “passive” means of urinary transport in that it is independent of active ureteral peristalsis. Acute
Obstruction
Following obstruction, the balance of active and passive forces within the upper urinary tract is disturbed, and the mechanics of normal transporting function is altered. The alterations that occur are not entirely the result of simple blockade and the back up of urine. Since the system is a dynamic, biological unit, obstruction will produce changes within the conduit wall that will effect the transmission of electrical impulses3 and the ability of the wall to generate contractions4 and actively propel urine. z-g This is clearly manifested during episodes of acute urinary obstruction. For
Ureteral Diameter mm
9.0
7.0 /
5.0 -
I
I
I 0 URETERAL
I
I
IO
TIME
TENSION
ot rest
I 20
= 3.24
X IO4
dynes/cm*
durfng contaction= 4.66
X IO4
dynes/cm2
t 30
I 40
I
I
50
I 60
(seconds)
FIGURE 3. Recording of nor-tic blood pressure, intraluminal ureteral pressure. outside ureteral diameter, and rc~,spiration.v in chronically obstructed ctrnine ureter. Chronically obstructed ureter gerwrcltc~s irwglclar clnd rctwkcv~etl contractions that produce intmlurninal prmwrrr ILYIIY~Sof .slight amplitudr~ or t1o~e what.wcr:er.
\vhen the llreter lxxwmes acutely o~eluded, the kidne!, continues to produce llrine that cannot freely pass the point of obstruction. This proximal to the obcauses a back up of urine struction and a buildup of hydrostatic pressure Lvithin the conduit lumen that is recorded as an illcrease in baseline intraluminal pressure iFig. 21.1.“.10.11 Th is increase in baseline intraluminal pressure and urine volume acts to distend the conduit walls increasing theil diameter. The initial response of the upper urinary conduit to these changes is threefold. First, there is an increase in resting or baseline \~a11 tension that is generated to maintain wall tone and structural integrity against the forces of dilatation: second, there is an increase in the contractile force that the conduit generates as evidenced l)!. increases in peak of contractile \~a11 tensions (Fig. 2); and third, there is an increase in tile frequency of contractions. Thus, \\.ithin the first few minutes of an activcb ureter-al occlusion, pressure rises within the upper urinary tract. ureteral walls increase their tone to resist dilatation, ant1 more forceful contractions are generated at an increased rate. \Vithin three to five minutes after acute hydrostatic pressure within ureteral otrclusion, thcb systenl continues to rise. and the concliiit
wall applies even greater ~tniounts of its tensile force toward the maintenance 01‘wall tone. As ;I result, less force is applied tLi- tht generation of contractions and they become w aker.’ After about ten to thirt!, minu tots of acute obstruction, hydrostatic pressllre within the conduit lumen becomes marked11 elevated (Fig. 2). This is accompanied l+ ;I lnarkrad increase in resting wall tension siilcc* the conduit applies essentially all of its foi~w toward the maintenance of its wall tone ;tncl struc*tural integrity leaving little or ii0 force fi)r the grw~ration of contractions. Thus, after th irt), minutes of acute occlusion, the dynamics Lvithin tht upper llrinary conduit is altered to Lvhere the rlreter ciiii no longer gencratt: significant contractions. and active transport is lost. At this point, \vhatever transportii~g function remains is entirely passive in natiirca and dependent upon hydrostatic, forces gerwratc~d 1)~ the kidney.~‘~‘2 The dynamics of the renal pelvis tlllrinq rble\xtions of pressure has recentl!. hwn studied in \.ivo in pigs 1,~. Djurhuus. “’ \\‘hen the renal pressure was increasing, thtl freqiienc’!, of pelvic action pottwtials increased up to t\vtbl\ e ,wtion potentials per minute. \;I:ith maintt*nance of tllrx stable hi,& pressiire, pel\ ic acti\.itTi- ftbll o\.er 3
FIGURE 4. (A) Mean baseline nd peak ureteral wall tensions and (B) mean baseline ,,_.,~““, , i..,l and peak intraluminal ureteral prxssuws in normal ureters, CHRONICALLYO;;;R;;~;~ND chronically obstructed ureters, OBSTRUCTED AND URETER INFECTED URETER INFECTED chronically obstructed and inWITH ANTIBIOTKS FOLLOWING WLIASE 01OBSTRUCTION fected ureters, chronically and infected obstructed ureters treated with antibiotics alone and those treated with release of their obstruction in conjunction with antibiotic therapy.
minute or so to original activity. It was postulated, rapid flow changes increased renal pelvic volume and stretched the muscle of the renal pelvis. Tension in the pelvic wall is increased which is reflected by increase in frequency of pelvic action potentials. Thereafter, an adaptation to stretch occurs (stress relaxation), and tension and frequency of action potentials reduce rapidly toward the original values. Chronic
Obstruction
As occlusion continues for days and weeks, dynamics within the system continue to change. Renal blood flow to the obstructed system is diminished.‘” This brings about a concomitant reduction in the glomerular filtration rate and intratubular hydrostatic pressure’” with increased reabsorption of urine into the venous and lymphatic channels all of which serve to lower intralurninal ureteral pressure. As a result, resting or baseline pressure within the chronically obstructed system is reduced to levels that approximate the range for normal, unobstructed ureters (Figs. 3 and 4).“,‘+ In addition, the chronically obstructed conduit regains its ability to generate contractions, although these contractions are less forceful than normal (Figs. 3 and 4).” A combination of the weakened nature of contractions and the fact that the conduit is distended secondary to dilatation makes it difficult for the chronically obstructed ureter to coapt its walls. The failure of complete coaptation impairs the ability of the ureter to constrict its
lumen effectively. As a result the increases in intraluminal pressure associated with contractions are somewhat less than those of a normal ureter (Figs. 3 and 4).“,6*“,“*1fi Since these pressure increases constitute the active, propulsive force which is directly responsible for the distal transport of urine, it becomes apparent that transporting function within the chronically obstructed system will be impaired. The magnitude of this impairment is dependent upon the degree of dilatation that must be overcome to achieve luminal constrictions and the degree to which contractibility is weakened. Most likely, decent contractile ability will be retained if obstruction produces smooth muscle hypertrophy within the conduit wall; whereas, if scar formation and collagen replacement of smooth muscle units occur as a result of obstruction, contractile capacity will be lost. l7 Recently, Hanna18 studied the histology of obstructed ureters and reports these findings from children at the Toronto Children’s Hospital. In light microscopic studies on 35 specimens of ureteropelvic junction obstruction, 23 per cent had no abnormality, 37 per cent had muscle continuity with replacement interrupted by connective tissue, 40 per cent had various abnormalities of either muscle bulk, muscle orientation, or the surrounding adventitia. Electron microscopy on these specimens of ureteropelvic junction obstruction showed excessive collagen between muscle cells, normal orientation of muscle cells with attenuated intimate contacts between cells, and normal nerve fibers. Refluxing megaureters (5
DOG # Blood Pressure mmHg
5057
LEFT
URETER
Obstruction
and Infection
200 I50 i 00 50 0 .I
40
3o
Ureteral Pressure mmHg
20
IO,, 01
,)
:
I
:
I
”
-
JOHN
OF OBSTRUCTION
G. ROSE,
ON URETERAL
FUNCTION
M.D.
JAY Y. GILLEN\V,4TEK,
M.D.
Frown the Department of Urology, Universit>Virginia School of Medicine, Charlottesville.
Impairment of Ilrinary flow will lead to significant renal damage, uremia, and death. It is this link hetwern the loss of renal function and obstnlction that has brought about a rather recent interest in the hydrodynamics of the iirinar\ q~stem. Hisk~rically. the urinary tract is cli\ided into an upper arid lower tract, consisting of the collecting system, rt~il pelvis, and ureter, on the OIIV hand, and the bladder and ~ux&ra, on the otller. From the urodynamic viewpoint, this system should he regarded as one physiologic unit that is completely interdependent. Olxtruction at any point along the tract hecause of increased volume and pressure proximally will affect all proximal lmits, alter their normal traILsporting function, and lead to Thus, while this article is nephron damage. concerned with changes that occur in the ureter following obstruction, these same changes apply whethrhr thcb obstrllction is primaril>. in the lipper tract or secondary to a lower tract ol~striiction. The impairment of urine flow within the upper urinary tract may result from either mechanical or fllnctional obstruction. Of the former. fixeign bodies, tumors, inflammatory processes. and congenital and acquired stnlc-
of b’irginia
tural anomalies lead the list; while of‘ the latter. l~laddel (1retero\,esical reflus and nerlrog~~nic are the most common couditiol(s. c~ncountered. In any case, the result is the same: the uppc11 tract does ilot drain satisfktoril;,~, alterations irr Ilreteral structure and function result, and renal filnction is ultimatelv afrec ted. Normal
Peristalsi:,
To gain some insight into the rt’t;Bct of ol)ctruction on transporting fiiuctiol~ \vithin the upper urinary conduit, it is necessq. to discuss normal ureteral function. Trallsporting function within the normal lIpper Ilrinx]c tract is accomplished by both active and passive forces. The active forces result from peristalsis within
5001 LEFT URE:TER
DOG #
--~
Ureteral Pressure mmHg
_
_
-
20 I5 10 ___Jq_ 5
0
__>L’.‘.
8: ~_
during contraciim=4.86
X IO4 dynes/cm2
t 3 MINUTES
POST
URETERAL
TENSION
t IO MINUTES
OCCLUSION
URETERAL
al rest = 3.24 X104 dynes/cm2 during contraction = 4 70 X IO” dyws/cmz
POST
OCCLUSION
TENSION
01 resl = 8.50
X IO4 dynes/cm2
dumq ccmiraclim = 8.34 X 104dyne&m2
intraluminal ureteral pressure, outside ureteral diameter, FIGURE 2. Recording of aortic blood pressure, and respirations in acutely obstructed canine ureter. After ureter is obstructed, baseline intraluminal ureteral pressure is built up behind obstruction, ureteral contractions diminish in face and eventually cease, and ureteral pressure waves also diminish in force and eventually cease.
the calyces, renal pelvis, and ureter, while the passive forces result from the filtration pressure in the kidney. Active peristalsis within the system is dependent upon the contractibility of smooth muscle within the walls of the conduit. As with other muscular organ systems, contractile activity within this system is preceded by an electrical impulse. As the impulse passes distally, a wave of depolarization occurs that induces the smooth muscle to contract causing the conduit to shorten and to oppose its walls. With each contraction, a lo-cm. section of ureter will shorten less than 1 mm.’ The role that this slight decrease in length plays in urine transport is probably minimal. More important is opposition of the conduit walls which results in luminal constriction. The force that acts to bring about opposition of the conduit walls is termed wall tension.’ Tension is a circumferentially directed force which, when increased, will effect luminal constrictions. Several phenomena result from these constrictions that serve to explain the mechanics of active* urine transport. First, urine in the conduit just proximal to constricting segments is formed into boluses. Second, intraluminal pressure within each constricting segment, and therefore behind each bolus, is markedly increased (Fig. 1). The increase in pressure behind each bolus acts to propel the
bolus toward the bladder as contractions pass distally. In this manner, the active transport of urine is accomplished. In addition to these propulsive forces that are dependent upon active peristalsis, urine within the upper urinary conduit is also transported by hydrostatic pressure that is generated through filtration in the kidney. As urine is formed and passes into the collecting ducts, it is transported to the calyces by pressure that is directly related to the glomerular filtration pressure and oncotic pressures. This intratubular hydrostatic pressure may be considered a “passive” means of urinary transport in that it is independent of active ureteral peristalsis. Acute
Obstruction
Following obstruction, the balance of active and passive forces within the upper urinary tract is disturbed, and the mechanics of normal transporting function is altered. The alterations that occur are not entirely the result of simple blockade and the back up of urine. Since the system is a dynamic, biological unit, obstruction will produce changes within the conduit wall that will effect the transmission of electrical impulses3 and the ability of the wall to generate contractions4 and actively propel urine. z-g This is clearly manifested during episodes of acute urinary obstruction. For
Ureteral Diameter mm
9.0
7.0 /
5.0 -
I
I
I 0 URETERAL
I
I
IO
TIME
TENSION
ot rest
I 20
= 3.24
X IO4
dynes/cm*
durfng contaction= 4.66
X IO4
dynes/cm2
t 30
I 40
I
I
50
I 60
(seconds)
FIGURE 3. Recording of nor-tic blood pressure, intraluminal ureteral pressure. outside ureteral diameter, and rc~,spiration.v in chronically obstructed ctrnine ureter. Chronically obstructed ureter gerwrcltc~s irwglclar clnd rctwkcv~etl contractions that produce intmlurninal prmwrrr ILYIIY~Sof .slight amplitudr~ or t1o~e what.wcr:er.
\vhen the llreter lxxwmes acutely o~eluded, the kidne!, continues to produce llrine that cannot freely pass the point of obstruction. This proximal to the obcauses a back up of urine struction and a buildup of hydrostatic pressure Lvithin the conduit lumen that is recorded as an illcrease in baseline intraluminal pressure iFig. 21.1.“.10.11 Th is increase in baseline intraluminal pressure and urine volume acts to distend the conduit walls increasing theil diameter. The initial response of the upper urinary conduit to these changes is threefold. First, there is an increase in resting or baseline \~a11 tension that is generated to maintain wall tone and structural integrity against the forces of dilatation: second, there is an increase in the contractile force that the conduit generates as evidenced l)!. increases in peak of contractile \~a11 tensions (Fig. 2); and third, there is an increase in tile frequency of contractions. Thus, \\.ithin the first few minutes of an activcb ureter-al occlusion, pressure rises within the upper urinary tract. ureteral walls increase their tone to resist dilatation, ant1 more forceful contractions are generated at an increased rate. \Vithin three to five minutes after acute hydrostatic pressure within ureteral otrclusion, thcb systenl continues to rise. and the concliiit
wall applies even greater ~tniounts of its tensile force toward the maintenance 01‘wall tone. As ;I result, less force is applied tLi- tht generation of contractions and they become w aker.’ After about ten to thirt!, minu tots of acute obstruction, hydrostatic pressllre within the conduit lumen becomes marked11 elevated (Fig. 2). This is accompanied l+ ;I lnarkrad increase in resting wall tension siilcc* the conduit applies essentially all of its foi~w toward the maintenance of its wall tone ;tncl struc*tural integrity leaving little or ii0 force fi)r the grw~ration of contractions. Thus, after th irt), minutes of acute occlusion, the dynamics Lvithin tht upper llrinary conduit is altered to Lvhere the rlreter ciiii no longer gencratt: significant contractions. and active transport is lost. At this point, \vhatever transportii~g function remains is entirely passive in natiirca and dependent upon hydrostatic, forces gerwratc~d 1)~ the kidney.~‘~‘2 The dynamics of the renal pelvis tlllrinq rble\xtions of pressure has recentl!. hwn studied in \.ivo in pigs 1,~. Djurhuus. “’ \\‘hen the renal pressure was increasing, thtl freqiienc’!, of pelvic action pottwtials increased up to t\vtbl\ e ,wtion potentials per minute. \;I:ith maintt*nance of tllrx stable hi,& pressiire, pel\ ic acti\.itTi- ftbll o\.er 3
FIGURE 4. (A) Mean baseline nd peak ureteral wall tensions and (B) mean baseline ,,_.,~““, , i..,l and peak intraluminal ureteral prxssuws in normal ureters, CHRONICALLYO;;;R;;~;~ND chronically obstructed ureters, OBSTRUCTED AND URETER INFECTED URETER INFECTED chronically obstructed and inWITH ANTIBIOTKS FOLLOWING WLIASE 01OBSTRUCTION fected ureters, chronically and infected obstructed ureters treated with antibiotics alone and those treated with release of their obstruction in conjunction with antibiotic therapy.
minute or so to original activity. It was postulated, rapid flow changes increased renal pelvic volume and stretched the muscle of the renal pelvis. Tension in the pelvic wall is increased which is reflected by increase in frequency of pelvic action potentials. Thereafter, an adaptation to stretch occurs (stress relaxation), and tension and frequency of action potentials reduce rapidly toward the original values. Chronic
Obstruction
As occlusion continues for days and weeks, dynamics within the system continue to change. Renal blood flow to the obstructed system is diminished.‘” This brings about a concomitant reduction in the glomerular filtration rate and intratubular hydrostatic pressure’” with increased reabsorption of urine into the venous and lymphatic channels all of which serve to lower intralurninal ureteral pressure. As a result, resting or baseline pressure within the chronically obstructed system is reduced to levels that approximate the range for normal, unobstructed ureters (Figs. 3 and 4).“,‘+ In addition, the chronically obstructed conduit regains its ability to generate contractions, although these contractions are less forceful than normal (Figs. 3 and 4).” A combination of the weakened nature of contractions and the fact that the conduit is distended secondary to dilatation makes it difficult for the chronically obstructed ureter to coapt its walls. The failure of complete coaptation impairs the ability of the ureter to constrict its
lumen effectively. As a result the increases in intraluminal pressure associated with contractions are somewhat less than those of a normal ureter (Figs. 3 and 4).“,6*“,“*1fi Since these pressure increases constitute the active, propulsive force which is directly responsible for the distal transport of urine, it becomes apparent that transporting function within the chronically obstructed system will be impaired. The magnitude of this impairment is dependent upon the degree of dilatation that must be overcome to achieve luminal constrictions and the degree to which contractibility is weakened. Most likely, decent contractile ability will be retained if obstruction produces smooth muscle hypertrophy within the conduit wall; whereas, if scar formation and collagen replacement of smooth muscle units occur as a result of obstruction, contractile capacity will be lost. l7 Recently, Hanna18 studied the histology of obstructed ureters and reports these findings from children at the Toronto Children’s Hospital. In light microscopic studies on 35 specimens of ureteropelvic junction obstruction, 23 per cent had no abnormality, 37 per cent had muscle continuity with replacement interrupted by connective tissue, 40 per cent had various abnormalities of either muscle bulk, muscle orientation, or the surrounding adventitia. Electron microscopy on these specimens of ureteropelvic junction obstruction showed excessive collagen between muscle cells, normal orientation of muscle cells with attenuated intimate contacts between cells, and normal nerve fibers. Refluxing megaureters (5
DOG # Blood Pressure mmHg
5057
LEFT
URETER
Obstruction
and Infection
200 I50 i 00 50 0 .I
40
3o
Ureteral Pressure mmHg
20
IO,, 01
,)
:
I
:
I
”
-
