Upper Tract Urodynamics

8/4/2019 Upper Tract Urodynamics

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UPPER TRACTURODYNAMICS

DR.R.SRIVATHSAN1ST YEAR

MCH UROLOGY


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CELLULAR ANATOMY

The primary functional anatomic unit of the ureteris the ureteral smooth muscle cell.

The cell is extremely small

250 to 400 m in length

5 to 7 m in diameter

Endoplasmic reticulum and sarcoplasmic reticulumfor Ca2+ storage.

Contractile proteins - actin and myosin

Dark bands along the cell surface are referred to as attachmentplaques

Caveolae - function is not known - ? Nutritive ? Ion transport. A double-layer cell membrane surrounds the cell -inner plasma

membrane & the outer basement membrane which is absent at areasof close cell-to-cell contact - intermediate junctions.


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General organization of the guinea-pig upper urinary tractLow magnification electron micrographsthrough the pelvi-calyceal junction (A), the proximal renal pelvis (B) and the ureter (C) of the guinea-

pig, illustrating the layered appearance of the epitheliUM

Klemm M F et al. J Physiol 1999;519:867-884


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DEVELOPMENT OF THE URETER

The ureter arises as an outpouching from the mesonephric

duct.

Ureteric bud formation & branching is induced by glial cellline derived neurotrophic factor (GDNF) derived from

adjacent metanephrogenic mesenchyme.

GDNF signals through the c-Ret receptor tyrosine kinasewhich results in increased phosphatidylinositol 3-kinase

(PI3K) activity and AKT/PKB phosphorylation.


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[Transforming growth factor (TGF-), hepatocyte

growth factor (HGF), fibroblast growth factors (FGF 1, 2,

7, and 10)

Matrix molecules such as heparin sulfate proteoglycans,

laminins, integrins, and matrix metalloproteinases(MMPs).

Apoptosis is involved in branching of the ureteric bud and

subsequent nephrogenesis.

Inhibitors of caspases inhibit ureteral bud branching.

Angiotensin II acting through the Angiotensin II type I

receptor is involved in the recanalisation process of ureter.


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ELECTRICAL ACTIVITY

Pacemaker Potentials and Pacemaker Activity:

Electrical activity arises in a cell either spontaneously or in response to

an external stimulus. Spontaneously pacemaker cell.

The ionic conduction underlying pacemaker activity is due to the

opening and slow closure of voltage activated L ca channels

amplified by prostanoids.

Nervous system has little or no role in maintaining pyeloureteral

motility.

The pacemaker cells are located near the pelvicalycealborderC-kit containing Cajal cell?

Latent pacemaker cells are present in all regions of the ureter


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Immunohistochemical staining for Kit in the rat

2009 by American Physiological Society


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URETERAL CONTRACTION

The ureter is a functional syncytium. Engelmann -stimulation contraction propagates

proximally and distally

But under normal conditions, electrical activity

arises proximally and is conducted distally thru

intermediate junctions

Gap junctions - groups of channels in the plasma

membrane - enable exchange of ions and smallmolecules and play a role in electrical coupling

between adjacent cells and in electromechanical

coupling (18-Glycyrrhetinic acid)


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URETERAL FUNCTION

Ureter transports urine from the kidney to the bladder. Under normal conditions,

ureteral peristalsis originates at pacemaker sites located inthe proximal portion of collecting systemelectricalactivity propagated distallymechanical event of

peristalsis - ureteral contraction which propels the bolusof urine distally.

Efficient propulsion of the urinary bolus depends on theureter's ability to coapt its walls completely

Urine passes into the bladder by way of the ureterovesicaljunction (UVJ), which, under normal conditions, permitsurine to pass from the ureter into the bladder but not viceversa.


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Conduction velocity in the ureter is 2 to 6 cm/sec

Vary with temperature, the time interval between stimuliand the pressure within the ureter.

CV : 1.5 to 2 m/sec in Purkinje fibers

: 10 to 100 m/sec in the dorsal and ventral roots.

Conduction is similar to that in cardiac tissue [evenWenckebach phenomenon (a partial conduction block) hasbeen demonstrated]


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MECHANICAL PROPERTIES OF URETER

Force-length relations: HYSTERESIS

Express the relation between the force developed bymuscle when it is stimulated under isometric conditionsand the resting length of the muscle at the time of

stimulation. The resting or contractile force developed at any given

length depends on the direction in which the change inlength is occurring and on the rate of length changehysteresis

For the ureter, at any given length, the resting force is lessand the contractile force is greater when the ureter isallowed to shorten than when the ureter is being stretched


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HYSTERESIS

Resting and contractile (active) forceof cat ureter during musclelengthening and shortening.

Force is on the ordinate;

change in length (L) is on theabscissa.

Solid symbols and solid lines showdata obtained during musclelengthening.

Open symbols and dashed lines showdata obtained during muscle

shortening. Circles show resting force, and

triangles show active or contractileforce.

Length and the direction of lengthchange influence resting andcontractile force


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Stress Relaxation:

When the ureter is stretched, the resting force increases. If the

length is kept constant at its new longer length after a

stretch, changes occur that result in a decrease in the

resting force, or stress relaxation


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Creep:

Ureteral muscle arrangement: longitudinal, circumferential

& spiral configuration.

After application of an intraluminal pressure, the ureter

increases in both length and diameterCREEP


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ROLE OF THE NERVOUS SYSTEM IN

URETERAL FUNCTION

The ureter is a syncytial type of smooth muscle without

discrete neuromuscular junctions

Ureteral peristalsis can occur without innervation.

[Transplant]

However, analysis of the data in the literature clearly

indicates that the nervous system plays at least a

modulating role in ureteral peristalsis


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Parasympathetic Nervous System

The prototypic cholinergic agonist is ACh, which serves as the

neurotransmitter at

(1) neuromuscular junctions of somatic motor nerves (nicotinic

sites)

(2) preganglionic parasympathetic and sympathetic neuroeffector

junctions (nicotinic sites)(3) postganglionic parasympathetic neuroeffector sites (muscarinic

sites).

Cholinergic agonists (ACh, methacholine,carbachol, bethanechol) -Excitatory effect on ureteral and renal pelvic function, that is, to

increase the frequency and force of contractions.

Atropine itself has little direct effect on ureteral activity effects are

frequently minimal and inconsistentno use in ureteric colic


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Sympathetic Nervous System

The ureter contains excitatory -adrenergic and inhibitory

-adrenergic receptors

(NA inc, IP dec)


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OTHERS

Tachykinins and calcitonin generelated peptide (CGRP)(peripheral endings of sensory nerves)

Tachykinins stimulate and CGRP inhibits electrical and

contractile activity.

Capsaicin-sensitive sensory nerves are located in the ureter

Renal pelvic sensory nerves contain both substance P and

CGRP

CGRP potentiates the afferent renal nerve activity responses

to substance P by retarding the metabolism of substance P


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RENAL PELVIC PHYSIOLOGY

The pressure within the renal pelvis is normally close to zero.

When this pressure increases (obstruction or reflux) pelvicalycesdilate.

The degree of hydronephrosis that develops depends on theduration, degree, and site of the obstruction (output pbl) or inputpbl (diuresis)

The higher the obstruction, the greater the effect on the kidney.

Intrarenal pelvis all the pressure will be exerted on theparenchyma.

Extrarenal pelvis only part of the pressure is exerted on theparenchyma (extrarenal renal pelvis embedded in fat dilates more

readily) In the earlier stages, the pelvic musculature hypertrophy in its

effort to force urine past the obstruction.

Later, however, the muscle becomes stretched and atonic (anddecompensated).


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Three phases of urine transport.

At flow rates from 0 to 2 ml per minute, transport occurs atlow pressure with a low resistance to flow through ureter.

Between 2 ml and 4 ml per minute significant increasein intrapelvic pressure due to increased resistance in theureter, probably caused by an impediment to passive filling(due to the previous ureteral contraction)

Above 4 ml per minute, transport takes place as acontinuous flow through the ureter, which functions as atube


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In many cases of UPJ obstruction there is no gross

narrowing at the UPJ but abnormal propagation of the

peristaltic impulse is a causative factor in the obstruction.

It appears possible that, at least in some instances,

disruption of cell-to-cell propagation of peristaltic activity

results in impairment of urine transport across the UPJ


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Theories of PUJO

Murnaghan - an alteration in the configuration of the musclebundles at the UPJ

Foote et al - decrease in musculature at the UPJ

Hanna - abnormalities in the musculature of the renal pelvis anddisruption of intercellular relations at the UPJ itself.

Murakumo - Increased accumulation of collagen (differences intype I and type III collagen)

Wang - decrease in nerves and in NGF messenger RNA(mRNA) expression

A vessel or adhesive band crossing the UPJ may potentiate thedegree of dilatation in any of the forms of UPJ obstruction


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URINE TRANSPORTBOLUS

At normal urine flows, the frequency of calyceal and renalpelvic contractions is greater than that in the upper ureter,and there is a relative block of electrical activity at the UPJ

At these flows, the renal pelvis fills; as renal pelvic

pressure rises, urine is extruded into the upper ureter,which is initially in a collapsed state

Ureteral contractile pressures that move the bolus of urineare higher than renal pelvic pressures, and a closed UPJmay be protective of the kidney in dissipating backpressure

from the ureter. As the flow rate increases, the block at the UPJ ceases and

a 1:1 correspondence between pacemaker and ureteralcontractions develops


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The contraction wave originates in the most proximalportion of the ureter and moves the urine in front of it in adistal direction.

The urine that had previously entered the ureter is formedinto a bolus.

In order to propel the bolus of urine efficiently, thecontraction wave must completely coapt the ureteral wallsand the pressure generated by this contraction waveprovides the primary component of what is recorded byintraluminal pressure measurements.

The bolus that is pushed in front of the contraction wavelies almost entirely in a passive, noncontracting part of theureter


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Baseline, or resting, ureteral pressure is approximately 0 to

5 cm H2O, and superimposed ureteral contractions ranging

from 20 to 80 cm H2O occur two to six times per minute.

At extremely high flows (Whitaker) the ureteral walls do

not coapt, and a continuous column of fluid, rather than a

series of boluses, is transported.

Effects of diuresis and obstruction appear to be

complementary and additive with respect to thedevelopment of renal pelvic and calyceal dilatation


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Griffiths andNotschaele (1983)


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Physiology of the Ureterovesical

Junction

Impediment of efficient bolus transfer across

the UVJ occurs

1. when there is an obstruction at the UVJ

2. when intravesical pressure is excessive,

3. when flow rates are so high as to exceedthe transport capacity of the normal UVJ.


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the pressure within the bolus increases & exceedsthe pressure in the contraction wave inability ofthe contraction wave to occlude the ureter

completely retrograde flow of urine from thebolus fraction of the urinary bolus passes acrossthe UVJ into the bladder.

large boluses occurring at high-flow conditionswould not be completely discharged into thebladder because the contraction wave pushing thebolus would be forced open and intraureteralreflux would occur.


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VESICAL PRESSURE

The pressure within the bladder during the storage phase isof paramount importance in determining the efficacy of

urine transport across the UVJ

The ureter has been shown to decompensate whenintravesical pressure approaches 40 cm H2O


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Thank you

Upper Tract Urodynamics

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