UPPER TRACT URODYNAMICS

DR.R.SRIVATHSAN 1ST YEAR MCH UROLOGY

CELLULAR ANATOMY
The primary functional anatomic unit of the ureter is 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 reticulum for Ca2+ storage. Contractile proteins - actin and myosin Dark bands along the cell surface are referred to as attachment plaques 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 areas of close cell-to-cell contact - intermediate junctions.

General organization of the guinea-pig upper urinary tractLow magnification electron micrographs through the pelvi-calyceal junction (A), the proximal renal pelvis (B) and the ureter (C) of the guineapig, illustrating the layered appearance of the epitheliUM

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

DEVELOPMENT OF THE URETER

The ureter arises as an outpouching from the mesonephric duct. Ureteric bud formation & branching is induced by glial cell line derived neurotrophic factor (GDNF) derived from adjacent metanephrogenic mesenchyme. GDNF signals through the c-Ret receptor tyrosine kinase which results in increased phosphatidylinositol 3-kinase (PI3K) activity and AKT/PKB phosphorylation.

 [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.

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 pelvicalyceal

border

C-kit containing Cajal cell?

Latent pacemaker cells are present in all regions of the ureter

Immunohistochemical staining for Kit in the rat

2009 by American Physiological Society

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 small molecules and play a role in electrical coupling between adjacent cells and in electromechanical coupling (18-Glycyrrhetinic acid)

URETERAL FUNCTION
Ureter transports urine from the kidney to the bladder. Under normal conditions, ureteral peristalsis originates at pacemaker sites located in the proximal portion of collecting system electrical activity propagated distally mechanical event of peristalsis - ureteral contraction which propels the bolus of urine distally. Efficient propulsion of the urinary bolus depends on the ureter's ability to coapt its walls completely Urine passes into the bladder by way of the ureterovesical junction (UVJ), which, under normal conditions, permits urine to pass from the ureter into the bladder but not vice versa.

 Conduction velocity in the ureter is 2 to 6 cm/sec Vary with temperature, the time interval between stimuli and 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 [even Wenckebach phenomenon (a partial conduction block) has been demonstrated]

MECHANICAL PROPERTIES OF URETER

Force-length relations: HYSTERESIS Express the relation between the force developed by muscle when it is stimulated under isometric conditions and 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 in length is occurring and on the rate of length change hysteresis For the ureter, at any given length, the resting force is less and the contractile force is greater when the ureter is allowed to shorten than when the ureter is being stretched

HYSTERESIS

Resting and contractile (active) force of cat ureter during muscle lengthening and shortening. Force is on the ordinate; change in length (L) is on the abscissa. Solid symbols and solid lines show data obtained during muscle lengthening. Open symbols and dashed lines show data obtained during muscle shortening. Circles show resting force, and triangles show active or contractile force. Length and the direction of length change influence resting and contractile force

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

Creep:
Ureteral muscle arrangement: longitudinal, circumferential & spiral configuration. After application of an intraluminal pressure, the ureter increases in both length and diameter

CREEP

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

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 inconsistent no use in ureteric colic

Sympathetic Nervous System

The ureter contains excitatory -adrenergic and inhibitory -adrenergic receptors (NA inc, IP dec)

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

RENAL PELVIC PHYSIOLOGY

The pressure within the renal pelvis is normally close to zero. When this pressure increases (obstruction or reflux) pelvicalyces dilate. The degree of hydronephrosis that develops depends on the duration, degree, and site of the obstruction (output pbl) or input pbl (diuresis) The higher the obstruction, the greater the effect on the kidney. Intrarenal pelvis all the pressure will be exerted on the parenchyma. Extrarenal pelvis only part of the pressure is exerted on the parenchyma (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 (and decompensated).

Three phases of urine transport. At flow rates from 0 to 2 ml per minute, transport occurs at low pressure with a low resistance to flow through ureter. Between 2 ml and 4 ml per minute significant increase in intrapelvic pressure due to increased resistance in the ureter, probably caused by an impediment to passive filling (due to the previous ureteral contraction) Above 4 ml per minute, transport takes place as a continuous flow through the ureter, which functions as a tube

 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

Theories of PUJO
Murnaghan - an alteration in the configuration of the muscle bundles at the UPJ Foote et al - decrease in musculature at the UPJ Hanna - abnormalities in the musculature of the renal pelvis and disruption of intercellular relations at the UPJ itself. Murakumo - Increased accumulation of collagen (differences in type 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 the degree of dilatation in any of the forms of UPJ obstruction

URINE TRANSPORT BOLUS

At normal urine flows, the frequency of calyceal and renal pelvic 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 urine are higher than renal pelvic pressures, and a closed UPJ may 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 ureteral contractions develops

 The contraction wave originates in the most proximal portion of the ureter and moves the urine in front of it in a distal direction. The urine that had previously entered the ureter is formed into a bolus. In order to propel the bolus of urine efficiently, the contraction wave must completely coapt the ureteral walls and the pressure generated by this contraction wave provides the primary component of what is recorded by intraluminal pressure measurements. The bolus that is pushed in front of the contraction wave lies almost entirely in a passive, noncontracting part of the ureter

 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 the development of renal pelvic and calyceal dilatation

Griffiths and Notschaele (1983)

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 exceed the transport capacity of the normal UVJ.

 the pressure within the bolus increases & exceeds the pressure in the contraction wave inability of the contraction wave to occlude the ureter completely retrograde flow of urine from the bolus fraction of the urinary bolus passes across the UVJ into the bladder. large boluses occurring at high-flow conditions would not be completely discharged into the bladder because the contraction wave pushing the bolus would be forced open and intraureteral reflux would occur.

VESICAL PRESSURE
The pressure within the bladder during the storage phase is of paramount importance in determining the efficacy of urine transport across the UVJ The ureter has been shown to decompensate when intravesical pressure approaches 40 cm H2O

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