11.2: Physiology

Normal voiding is a complex interaction of supraspinal and spinal control. This will cause relaxation of the urethra and sustained contraction of the detrusor to facilitate complete empting of the bladder.

Neural control of normal micturition is a complicated system. A simplified summary is as follows:

The supra-pontine control centres in the frontal cortex of the limbic area and the cerebellum have an inhibitory effect on the function of the bladder. The pons has two regions, the M- region for stimulation and the L- region for inhibition. The spinal cord will relay the sympathetic, parasympathetic and somatic fibers to the lumbar and sacral areas and the parasympathetic system will stimulate the detrusor muscle whereas the sympathetic system will increase outflow resistance. The somatic system has control of the rhabdo muscle of the urethra as well as control of the pelvic floor muscles. All 3 systems must work in balance to create normal storage and voluntary voiding of the bladder.

A neurogenic bladder can be described as the effect of neurological disease on lower urinary tract function.

To understand the function better the different systems will be discussed separately.

Central nervous system (CNS)

The cortical pathways originate in the pre central gyrus, lateral prefrontal cortex and anterior cingulate gyrus. These centers mainly inhibit the midbrain area, the so-called pontine micturition center (PMC). CNS control of micturition centers around the middle pons. Barrington showed in cats that the motor tone of the bladder arises in this region. The Pontine Micturition Centre (PMC) is called the M-region and causes stimulation of detrusor muscle and relaxation of the sphincter. Stimulation of this center will lower urethral pressure, inhibit pelvic floor contraction and stimulate detrusor contraction.

Stimulation on the same level as the M-Region but more lateral, the so called L-region, will stimulate Onuf’s nucleus to contract the urethra. Thus the midbrain will control either storage or emptying function of the bladder through the M and L pontine micturition regions.

CNS control centers around the middle pons, where Barrington showed in cats that the motor tone of the bladder arises, is the most important.

The midbrain gets inhibitory and stimulatory control from many different regions in the brain namely frontal cortex, cerebellum, and hypothalamus.
The main neurotransmitters in the CNS are glutamate for stimulation and GABA and glycine for inbibition.

A central concept in the development and organization of the brain is plasticity. This means that the brain can adjust its hardwiring through conditioning or external stimuli.

This is mainly achieved by the organization of the interconnections through the white matter. It is now understood that the white matter is an extremely dynamic part of brain development.

The changes of aging on the brain have a variable effect and may cause abnormal sensory perceptions or reduced inhibition of bladder function.

Parasympathetic System

Parasympathetic stimulation will start in the M-regions of the pontine micturition center to the intermedial grey matter of the spinal cord at level S2-4.These fibres will then emerge from the piriformis muscle overlying the sacral foramina and form the pelvic plexus which in turn supplies the pelvic organs. The fibres terminate in ganglia in the wall of the bladder making it vulnerable to injuries of the bladder e.g. overstretching, infection or fibrosis.

In the ganglia, the nerves are stimulated by nicotinic acetylcholine receptors. Other neurotransmitters are also active at ganglia level but not as important.
Postganglionic parasympathetic fibres diverge and store neurotransmitters in synaptic vesicles. On electrical impulse the vesicle binds to the synaptic membrane and deposits the acetylcholine in the synapse to stimulate muscarinic receptors on the muscle fibres stimulating muscle contraction through intracytoplasmic calcium release.

Sympathetic system

Sympathetic stimulation reaches the bladder through preganglionic fibres from thoracolumbar spinal segments that synapse in paravertebral and paravertebral sympathetic pathways. Postganglionic neurons reach the upper vagina, bladder, proximal urethra and lower ureter through the hypogastric and pelvic plexuses. The sympathetic preganglionic neurotransmitter is mainly acethylcholine, acting on nicotinic receptors and post ganglionic transmitters, primarily norepinephrine. Stimulation of B-adrenergic receptors in the bladder causes relaxation of the smooth muscle and stimulation of alpha-one receptors in the bladder base and smooth muscle of the urethra causing muscle contraction.

Norepinephrine also suppress secretion of the presynaptic parasympathetic cholinergic neurotransmitter. Urine storage is thus attained by detrusor relaxation, urethral muscle contraction and inhibition of parasympathetic stimulation all through sympathetic stimulation.

Somatic innervation Skeletal muscle is present in the distal portion of the urethra and pelvic-floor muscles. The innervations come from Onuf’s somatic nucleus in the anterior horn of S2-4 segments. This nucleus gives rise to the pudendal nerve, which supplies the rhabdo urethral sphincter. Important neurotransmitters include serotonin and norepinephrine.

These increase the effect of the excitatory neurotransmitter, glutamate, on pudendal motor neurons. The effects on the rhabdo sphincter are achieved by acetylcholine stimulation of nicotinic cholinergic receptors.

Sensory pathways

The two important sensory feedbacks are transported to the central nervous system through the parasympathetic and sympathetic system. They have a contra and ipsilateral supply.

Proprioceptive endings are present in collagen bundles in the bladder and these are responsible for stretch and contraction sensations.
Free nerve endings (C fibres) are in the mucosa and s

ubmucosa and stimulated through pain and temperature. The sensory endings contain acetylcholine and substance P. Urethral sensation is transmitted mainly through pudendal nerve.

Central areas that receive bladder and urethral sensation are the periaqueductal grey matter (PAG), insula and anterior cingulate gyrus. An area in the frontal cortex is also activated at times of filling. A study of both normal patients and those with overactivity of the bladder showed different areas of predominant activity. Using functional magnetic resonance imaging (fMRI)4), the insula is stimulated to a greater extent anteriorly with unpleasant bladder sensations. These sensations are received by the PAG and mapped in the insula. It would therefore seem that not only normal sensory impulses but also abnormal impulses or abnormal mapping are responsible for overactivity of the bladder. It is easy to understand that diffuse neurologic disorders might have an effect on the perception of sensory impulses of a normal LUT.