Saturday, January 28, 2012

Physiology of Continence

Factors maintaining urinary continence

Urinary continence depends on many physiological factors that are not equally important or necessarily operative at the same time but all act in concert together to preserve the two main functions of the lower urinary tract that maintain continence, storage and emptying. These factors are partially local and partially due to central coordination and include:
1. Functioning bladder (storage and emptying). This depends mainly on bladder compliance, detrusor stability and contractility.
2. Intact urethral sphincters, mucosa and submucosa.
3. Intact pelvic floor muscles (Peri-urethral muscles).
4. Neural control (autonomic and somatic innervations)
1-   Physiology of the Bladder in relation to continence
The bladder is composed of mucosa, lamina propria, smooth muscle cells, nerve endings, fibroblasts and extracellular matrix. It is this dynamic combination of elements interacting together that makes the bladder is one of the most compliant organs in the body, enabling its volume to expand dramatically without significant increases in pressure until a critical point is reached .
The detrusor (smooth) muscles of bladder consist of sheets containing many small spindle-shaped cells that contain actin (thin filament), myosin (thick filament) and cytoskeletal intermediate filaments that assist in transmission of the force generated during contraction. The actin and myosin filaments are arranged as myofibrils that cross obliquely in a lattice-like arrangement. The contraction of smooth muscle is slow, sustained, and resistant to fatigue maintaining a steady level of contraction and tone.
Tone is important in maintaining the capacity of the bladder and depends on many factors, some intrinsic and some extrinsic. Extrinsic factors include activity in the autonomic nerves and circulating hormones; Intrinsic factors include the response to stretch, local metabolites, locally secreted agents such as nitric oxide, and temperature .
2-   Physiology of the urethra in relation to continence
The urethra is composed of mucosa, submucosa, smooth and striated muscles.
The urethral mucosa and submucosa function as a filler substance to effectively close the urethral lumen after narrowing of lumen by urethral sphincter .
Impaired arterial blood supply to the urethra decreases the intraluminal urethral pressure due to decreased vascular filling and hypoxic effect on the urethral smooth muscle .
The proximal urethral sphincter has inner longitudinal and outer circular smooth muscle layers. Contraction of the inner longitudinal smooth muscle plays a role in resting continence, stabilizing the urethra and allowing force generated by the circular muscle elements to occlude the lumen .
The distal urethral sphincter consists of an inner longitudinal thin smooth muscle layer and an outer circular striated muscle composed predominately of slow-twitch fibers (type I) which are responsible for continence at rest. Despite the horseshoe configuration of the DUS (see the anatomy), the urethral pressure recording at the external sphincter during bladder filling increases uniformly along the entire circumference like an iris. Hypogastric nerve stimulation augments this pressure, suggesting a role for adrenergic receptors and sympathetic nerves in the function of the external urethral sphincter .

3-   Physiology of the Striated Muscles of the Pelvic Floor (Peri-urethral muscles)
The peri-urethral striated muscles of the pelvic floor contain predominatly fast-twitch fibres (type IIa) and few slow-twitch fibers. They are adapted for the rapid recruitment of motor units required during increases in abdominal pressure (active continence).
It has been speculated that the successful treatment of stress incontinence by pelvic floor muscle training (PFMT) or electro-stimulation (ES) is caused by the conversion of fast-twitch fibers to slow-twitch fibers that maintain continence at rest .
Types of Striated Muscle Fibers
The Striated muscle fibers are classified into: slow-twitch fibers and fast-twitch fibers.
The slow-twitch fibers (type I): found in greater percentage in muscles that require sustained tension, such as the DUS and to a lesser degree in the pelvic floor muscles.
These muscle fibers are recruited slowly, fatigue slowly and can perform high rates of oxidative metabolism because they possess less of the myosin ATPase activity and contain an increased expression of a slow iso-form of the Ca2+-ATPase.
The fast-twitch fibers (type II): are found mainly in pelvic floor muscles that maintain continence in stress conditions when intra-abdominal pressure is abruptly increased by adding to sphincter tone rapidly (Such conditions as cough, abdominal straining or voluntary interruption of the urinary stream). Fast-twitch fibers can be recruited rapidly, tend to fatigue rapidly and perform predominantly anaerobic metabolism. Fast-twitch fibers are rich in myosin ATPase that catalyzes the actin-myosin interaction and  fast iso-form of the Ca2+-ATPase. Fast-twitch fibres can be classified into fatigue-resistant (type IIa) as pelvic levator and fatiguable (type IIb) which is not related to continence .

Micturition Cycle (Fig. 1)
The micturition cycle is divided into two relatively discrete phases: Bladder filling phase and Bladder emptying phase.

Figure (1):  Mechanism of storage and voiding phase reflexes.
A, Storage reflexes. distention of bladder produces low-level bladder afferent firing which stimulates the sympathetic outflow to bladder outlet (base and urethra) and pudendal outflow to  external urethral sphincter. These responses occur by spinal reflex pathways and represent “guarding reflexes,” which promote continence. Sympathetic firing also inhibits detrusor muscle.
B, Voiding reflexes. At initiation of micturition, intense vesical afferent activity activates PMC, which inhibits spinal guarding reflexes and stimulates parasympathetic outflow to bladder and internal sphincter smooth muscle. Maintenance of voiding reflex is through ascending afferent input from the spinal cord, which may pass through the periaqueductal gray matter (PAG) before reaching the PMC .

4-    The Neural Control of Micturition & Continence (Fig. 2)
The apparently simple lower urinary tract function comprising the storage and periodic elimination of urine is under a complex regulatory control of neural system that involves: central and peripheral neural control.

Figure (2): Neural control of the lower urinary tract. Showing the somatic, sympathetic and parasympathetic peripheral nerves; the pontine micturition centre, the periaqueductal gray and the suprapontine areas involved in control of storage and voiding of urine. There are extensive interactions at all levels (not shown) (Chapple et al., 2009).

A)     Central (Spinal and Sura-spinal) Control of Micturition (Fig. 3)
The spinal center of micturition is located in the lumbo-sacral spinal cord and responsible of voiding reflexes. It is controlled by higher supraspinal micturition centers.
The supra-spinal centers controlling micturition include the pontine micturition center (PMC) (Fig. 3), the periaqueductal grey (PAG) and supra-pontine centers which include the frontal cortex, the hypothalamus, the para-central lobule, the limbic system and the cingulate gyrus .

Figure (3): Pontine micturition center (Horizontal section showing significantly increased blood flow with PET in the dorsal pons during micturition). L, left side; R, right side of the brain .

Role of spinal center in control of micturition
The spinal micturition center controls a number of involuntary reflexes. With bladder filling, the sympathetic activity is increased, the parasympathetic activity is inhibited and the pudendal (somatic) neurons are activated (guarding reflex). Micturition reflex is also a spinal reflex which is controlled by higher supra-spinal centers .
Role of supra-spinal centers in control of micturition
The brain supra-spinal centers allow for the perception of bladder fullness, determine the “social correctness” of the micturition act and coordinate the activities of the striated and smooth muscles involved in the micturition reflex to maintain a reciprocal relationship between the bladder and the urethral outlet .
The PAG is an integrative brain center that receives sensory stimuli of bladder fullness via the spinal cord then sends it to the PMC.
The PMC is essential in co-ordinating the micturition process and is itself under the control of the suprapontine area .

B)   Peripheral Control of Micturition (Fig. 4)
The bladder is supplied by three sets of nerve fibres: the pelvic nerve, the pudendal nerve and the hypogastric nerve.

Figure (4): The sympathetic, parasympathetic, and somatic innervation of the urogenital tract of the male.
Sympathetic preganglionic pathways emerge from lumbar cord to symp. chain ganglia (SCG) then through inferior splanchnic nerves (ISN) to infer. mesenteric ganglia (IMG). Pre- and post-ganglionic sympathetic axons travel in hypogastric nerve (HGN) to pelvic plexus and urogenital organs.
Parasympathetic preganglionic axons originate in the sacral cord & pass in pelvic nerve to ganglion cells in pelvic plexus and to distal ganglia in organs.
Sacral somatic pathways are contained in pudendal nerve, which innervates penis and ischiocavernosus (IC), bulbocavernosus (BC), and distal urethral sphincter (DUS) muscles. The pudendal and pelvic nerves also receive postganglionic axons from the caudal sympathetic chain ganglia. These three sets of nerves contain afferent axons from lumbosacral dorsal root ganglia. (PG: prostate gland; U: ureter; VD: vas deferens).
1- The pelvic nerves (S2–S4)–(Parasympathetic):
The principal nerve supply of the bladder is by way of the pelvic nerves, which connect with the spinal cord through the sacral plexus, mainly connecting with cord segments S-2 and S-3. The pelvic nerves contains both sensory and motor nerve fibers. The sensory fibers detect the degree of stretch in the bladder wall and posterior urethra and responsible for initiating the reflexes that cause bladder emptying. The motor nerves are parasympathetic fibers that innervate the detrusor muscle . 
2- The pudendal nerve (Somatic):
Motor innervation to skeletal muscle fibers of the distal urethral sphincter is transmitted through the pudendal nerve.
3- The hypogastric nerves (T11–L2)-(Sympathetic):
Sympathetic innervation emerges from the sympathetic chain through the hypogastric nerves, connecting mainly with the L-2 segment of the spinal cord. These sympathetic fibers stimulate mainly the blood vessels and have little to do with bladder contraction .



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