Medical Physiology, 3rd Edition

The Ureters and Bladder

As discussed in Chapters 44 and 45, the epithelium of the gastrointestinal (GI) system continues to modify the contents of the GI tract up until the point where the contents finally exit the body. The situation is very different in the mammalian urinary system. By the time the fluid leaves the most distal portion of the collecting duct, the fluid has the composition of final urine. Thus, the renal pelvis, ureters, bladder, and urethra do not substantially modify the urine volume or composition.

The ureters propel urine from the renal pelvis to the bladder by peristaltic waves conducted along a syncytium of smooth-muscle cells

The ureters serve as conduits for the passage of urine from the renal pelvis into the urinary bladder (see Fig. 33-1A). Located in the retroperitoneum, each ureter loops over the top of the common iliac artery and vein on the same side of the body and courses through the pelvis. The ureters enter the lower posterior portion of the bladder (ureterovesical junction), pass obliquely through its muscular wall, and open into the bladder lumen 1 to 2 cm above, and lateral to, the orifice of the urethra (Fig. 33-11A). The two ureteral orifices, connected by a ridge of tissue, and the urethral orifice form the corners of a triangle (bladder trigone). A flap-like valve of mucous membrane covers each ureteral orifice. This anatomical valve, in conjunction with the physiological valve-like effect created by the ureter's oblique pathway through the bladder wall, prevents reflux of urine back into the ureters during contraction of the bladder.

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FIGURE 33-11 A, Anatomy of the ureters and bladder. B, Ureteral smooth-muscle cells generally have a resting membrane potential of about −60 mV, mainly determined by a high K+ membrane permeability. Na+ channels speed the upstroke of the action potential, although Ca2+ channels are mainly responsible for the action potential.

The lumen of each ureter is lined by transitional epithelium, which is above a submucosal layer of connective tissue, as well as an inner longitudinal and an outer circular layer of smooth muscle. Ureteral smooth muscle functions as a syncytium and is thus an example of unitary smooth muscle (see pp. 243–244). Gap junctions (see pp. 158–159) conduct electrical activity from cell to cell at a velocity of 2 to 6 cm/s. Chemical or mechanical stimuli (e.g., stretch) or a suprathreshold membrane depolarization may trigger an action potential (see Fig. 33-11B) of the plateau type (see p. 244).

Contraction of ureteral smooth muscle is similar to that of other smooth muscle (see pp. 247–248), in which Ca2+-calmodulin activates myosin light-chain kinase (MLCK). cAMP-dependent protein kinase (protein kinase A, or PKA) can phosphorylate MLCK, thereby lowering the affinity of MLCK for Ca2+-calmodulin and impairing phosphorylation of myosin light chains. This mechanism may, at least in part, account for the relaxing effect of cAMP on smooth muscle.

Ureteral peristaltic waves originate from electrical pacemakers in the proximal portion of the renal pelvis. These waves propel urine along the ureters and into the bladder in a series of spurts at frequencies of 2 to 6 per minute. The intraureteral hydrostatic pressure is 0 to 5 cm H2O at baseline but increases to 20 to 80 cm H2O during peristaltic waves. Blockade of ureteral outflow to the bladder, as by a kidney stone, causes the ureter to dilate and increases the baseline hydrostatic pressure to 70 to 80 cm H2O over a period of 1 to 3 hours. This pressure is transmitted in retrograde fashion to the nephrons, creating a stopped-flow condition in which glomerular filtration nearly comes to a halt. Hydronephrosis, dilation of the pelvis and calyces of the kidney, can evolve over hours to days. Patients complain of severe pain (renal colic) resulting from distention of involved structures. If not cleared, the obstruction can cause marked renal dysfunction and even acute renal failure. With persistent obstruction, the pressure inside the ureter declines to a level that is only slightly higher than the normal baseline. Even though the patient produces no urine (anuria), glomerular filtration continues, albeit at a markedly reduced rate, a condition reflecting a balance between filtration and fluid reabsorption by the tubules.

Although ureteral peristalsis can occur without innervation, the autonomic nervous system can modulate peristalsis. As in other syncytial smooth muscle, autonomic control of the ureters occurs by diffuse transmitter release from multiple varicosities formed as the postganglionic axon courses over the smooth-muscle cell. Sympathetic input (via aortic, hypogastric, and ovarian or spermatic plexuses) modulates ureteral contractility as norepinephrine acts by excitatory α-adrenergic receptors and inhibitory β-adrenergic receptors. Parasympathetic input enhances ureteral contractility via acetylcholine, either by directly stimulating muscarinic cholinergic receptors (see p. 341) or by causing postganglionic sympathetic fibers to release norepinephrine, which then can stimulate α adrenoceptors. Some autonomic fibers innervating the ureters are afferent pain fibers. In fact, the pain of renal colic associated with violent peristaltic contractions proximal to an obstruction is one of the most severe encountered in clinical practice.

Sympathetic, parasympathetic, and somatic fibers innervate the urinary bladder and its sphincters

The urinary bladder consists of a main portion (body) that collects urine and a funnel-shaped extension (neck) that connects with the urethra (see Fig. 33-11A). A transitional epithelium lines the bladder lumen. Three poorly defined layers of smooth muscle make up the bulk of the bladder wall, the so-called detrusor muscle. At the lower tip of the trigone, the bladder lumen opens into the posterior urethra (i.e., distal part of bladder neck), which extends over 2 to 3 cm. The wall of the posterior urethra contains smooth-muscle fibers of the detrusor muscle interspersed with elastic tissue, together forming the internal sphincter (Table 33-3). Immediately adjacent is the external sphincter, made up of voluntary, mainly slow-twitch striated-muscle fibers.

TABLE 33-3

Urethral Sphincters

 

INTERNAL SPHINCTER

EXTERNAL SPHINCTER

Type of muscle

Smooth

Skeletal

Nerve reaching the structure

Hypogastric

Pudendal

Nature of innervation

Autonomic

Somatic

In humans, bladder smooth muscle appears to lack gap junctions, which would indicate the absence of electrotonic coupling between cells. Thus, bladder smooth muscle is probably “multiunit” (see p. 243), with a 1 : 1 ratio between nerve endings and smooth-muscle cells. Contraction of bladder smooth muscle is typical of that of other smooth-muscle cells.

The bladder and sphincters receive sympathetic and parasympathetic (autonomic) as well as somatic (voluntary) innervation (Fig. 33-12). The sympathetic innervation to the bladder and internal sphincter arises from neurons in the intermediolateral cell column of the tenth thoracic to the second lumbar spinal cord segment (see pp. 335–339). The preganglionic fibers then pass via lumbar splanchnic nerves to the superior hypogastric plexus, where they give rise to the left and right hypogastric nerves. These nerves lead to the inferior hypogastric/pelvic plexus, where preganglionic sympathetic fibers synapse with postganglionic fibers. The postganglionic fibers continue to the bladder wall via the distal portion of the hypogastric nerve. This distal portion also contains the preganglionic parasympathetic axons discussed in the next paragraph.

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FIGURE 33-12 Autonomic and somatic innervation of the bladder.

The parasympathetic innervation of the bladder originates from the intermediolateral cell column in segments S2 through S4 of the sacral spinal cord (see p. 338). The parasympathetic fibers approaching the bladder via the pelvic splanchnic nerve are still preganglionic. They synapse with postganglionic neurons in the body and neck of the urinary bladder.

The somatic innervation originates from motor neurons arising from segments S2 to S4. Via the pudendal nerve, these motor neurons innervate and control the voluntary skeletal muscle of the external sphincter (see Fig. 33-12).

Bladder filling activates stretch receptors, initiating the micturition reflex, a spinal reflex under control of higher central nervous system centers

Bladder tone is defined by the relationship between bladder volume and internal (intravesical) pressure. One can measure the volume-pressure relationship by first inserting a catheter through the urethra and emptying the bladder, and then recording the pressure while filling the bladder with 50-mL increments of water. The record of the relationship between volume and pressure is a cystometrogram (Fig. 33-13, blue curve). Increasing bladder volume from 0 to ~50 mL produces a moderately steep increase in pressure. Additional volume increases up to ~300 mL produce almost no pressure increase; this high compliance reflects relaxation of bladder smooth muscle. At volumes >400 mL, additional increases in volume produce steep increments in passive pressure. Bladder tone, up to the point of triggering the micturition reflex, is independent of extrinsic bladder innervation.

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FIGURE 33-13 A cystometrogram.

Cortical and suprapontine centers in the brain normally inhibit the micturition reflex, which the pontine micturition center (PMC) coordinates. The PMC controls both the bladder detrusor muscle and the urinary sphincters. During the storage phase, stretch receptors in the bladder send afferent signals to the brain via the pelvic splanchnic nerves. One first senses the urge for voluntary bladder emptying at a volume of ~150 mL and senses fullness at 400 to 500 mL. Nevertheless, until a socially acceptable opportunity to void presents itself, efferent impulses from the brain, in a learned reflex, inhibit presynaptic parasympathetic neurons in the sacral spinal cord that would otherwise stimulate the detrusor muscle. Voluntary contraction of the external urinary sphincter probably also contributes to storage.

The voiding phase begins with a voluntary relaxation of the external urinary sphincter, followed by relaxation of the internal sphincter. When a small amount of urine reaches the proximal (posterior) urethra, afferents signal the cortex that voiding is imminent. The micturition reflex now continues as pontine centers no longer inhibit the parasympathetic preganglionic neurons that innervate the detrusor muscle. As a result, the bladder contracts, expelling urine. Once this micturition reflex has started, the initial bladder contractions lead to further trains of sensory impulses from stretch receptors, thus establishing a self-regenerating process (see Fig. 33-13, red spikes moving to the left). At the same time, the cortical centers inhibit the external sphincter muscles. Voluntary urination also involves the voluntary contraction of abdominal muscles, which further raises bladder pressure and thus contributes to voiding and complete bladder emptying.

The basic bladder reflex that we have just discussed, although inherently an autonomic spinal cord reflex, may be either facilitated or inhibited by higher centers in the central nervous system that set the level at which the threshold for voiding occurs.

Because of the continuous flow of urine from the kidneys to the bladder, the function of the various sphincters, and the nearly complete emptying of the bladder during micturition, the entire urinary system is normally sterile (Box 33-1).

Box 33-1

Pathophysiology of Micturition

Lesions in the nervous system can lead to bladder dysfunction, the characteristics of which will depend on the site of the neural lesion. Three major classes of lesions can be distinguished:

1. Combined afferent and efferent lesions. Severing both afferent and efferent nerves initially causes the bladder to become distended and flaccid. In the chronic state of the so-called decentralized bladder, many small contractions of the progressively hypertrophied bladder muscles replace the coordinated micturition events. Although small amounts of urine can be expelled, a residual volume of urine remains in the bladder after urination.

2. Afferent lesions. When only the sacral dorsal roots (sensory fibers) are interrupted, reflex contractions of the bladder in response to stimulation of the stretch receptors are totally abolished. The bladder frequently becomes distended, the wall thins, and bladder tone decreases. However, some residual contractions remain because of the intrinsic contractile response of smooth muscle to stretch. As a rule, a residual urine volume is present after urination.

3. Spinal cord lesions. The effects of spinal cord transection (e.g., in paraplegic patients) include the initial state of spinal shock in which the bladder becomes overfilled and exhibits sporadic voiding (“overflow incontinence”). With time, the voiding reflex is re-established, but with no voluntary control. Bladder capacity is often reduced and reflex hyperactivity may lead to a state called spastic neurogenic bladder. Again, the bladder cannot empty completely, so that significant residual urine is present. Urinary tract infections are frequent because the residual urine volume in the bladder serves as an incubator for bacteria. In addition, during the period of “overflow incontinence,” before the voiding reflex is re-established, these patients have to be catheterized frequently, which further predisposes to urinary tract infections.