Micturition

Question 1

What is micturition?

Answer 1

Micturition is the act of urination (emptying the bladder). The basic process is broken down into:

1) urine made in the kidneys (1 ml/min)
2) urine stored in the bladder
3) urine released from the bladder

Question 2

Describe the basic process of micturition.

Answer 2

Urine passes from the collecting ducts of the renal tubules into the renal pelvis. The renal pelvis is funnel-like dilated proximal part of the ureter in the kidney. Contraction of the smooth muscle of the pelvis aids in the movement of the urine into the ureter.

As the ureter gets distended, the smooth muscle which is arranged circularly contracts. This contraction closes the junction between the pelvis and the ureter, and pushes urine further into the ureter, causing distension and further contraction. A peristaltic wave is initiated and propagated along the length of the ureter until it propels urine into the bladder. Peristaltic waves are initiated about 5 times per minutes from the renal pelvis.

Ureters open at an oblique angle to the wall of the bladder. This arrangement helps ensure that when the pressure within the bladder rises, the ureters are compressed, so preventing the reflux of urine back up into the ureters. Ureteric peristalsis is myogenic in origin, ie. originating in the smooth muscle. The ureters seem to function normally when their extrinsic nerves are cut, so neural control by the CNS is not important. We still require the coordination of peristaltic waves and the response to changes in volume of urine produced by the kidney.

Question 3

Describe kidney stones.

Answer 3

Kidney stones (renal calculi) are the most common disorder of the urinary tract [note that they are not the same as gall stones]. They develop from crystals that separate from the urine within the urinary tract.
Normal urine contains inhibitors (citrate) to prevent this.

Calcium is present in nearly all stones (80%), usually as calcium oxalate, or less often as calcium phosphate. Others are made up of uric acid (<10%), struvite (<10%) and cystine (<5%).

They are more common in men than women (2-3:1) due to the testosterone levels. It is caused by poor urine output/ obstruction, altered urinary pH, low concentration of inhibitors, infection, and excess dietary intake of stone-forming substances.

Question 4

What are the symptoms of kidney stones?

Answer 4

Kidney stones can form anywhere within the urinary tract: kidney, ureter or in the bladder.

The symptoms are:

• dysuria (painful urination)
• haematuria
• loin pain/ back pain
• reduced urine flow
• urinary tract obstruction: pressure reaches 50 mmHg which causes considerable pain known as ‘renal colic’
• if the stone approaches the tip of the urethra, the intense pain can inhibit micturition; this is known as ‘strangury’

Question 5

What are some key features of the bladder?

Answer 5

1) The mucosal lining of the bladder is transitional epithelium which is capable of stretching without damage. It consists of ridges that flatten out the bladder as it fills. It has unique properties: it is very impermeable to salts and water, so there is no exchange between the urine and the capillaries of the bladder wall.

2) The muscle coat around, lining the epithelium, is made up of bundles of smooth muscle interlacing and running in various directions. This is considered as a single structure known as the detrusor muscle.
The mucosal layer is generally loosely attached to the underlying muscle except at the base of the bladder. This is where the entrance of the 2 ureters and the exit of the urethra form a triangle known as the ‘trigone’. This is where the mucosa is firmly attached, making the thickest and least distensible part of the bladder.

3) The outlet of the bladder into the urethra is guarded by 2 sphincters: the internal and external sphincter.

Question 6

Describe the two sphincters of the bladder.

Answer 6

INTERNAL SPHINCTER:
The internal sphincter is formed by a loop of muscle that is an extension of the detrusor, such that when the detrusor contracts, the fibres forming this loop shorten and open the sphincter.
It is not under voluntary control.

EXTERNAL SPHINCTER:
The external sphincter is composed of skeletal muscle and is continuous with the levator ani (a muscle situated on either side of the pelvis).
It has 2 striated muscles, the compressor urethrae and the bulbocavernosus. They surround the urethra; they are responsible for continence, so they are under conscious, voluntary control.

Females require both sphincters for effective continence, but males can manage with either sphincter intact because of different anatomical arrangement concerning the urethra.

Question 7

Describe the (anatomical) differences between a male and female bladder.

Answer 7

The female urethra is a much simpler structure than the male urethra because it only carries urine, whereas the male urethra also serves as a duct for the ejaculation of semen as part of its reproductive function.

In women, these structures around the neck of the bladder are the end of the system and point of exit if urine from the body. The external sphincter is poorly developed, and women are more prone to incontinence, particularly after childbirth (keep doing pelvic floor exercises??).

In men, the urethra continues through the penis - urine remaining in the urethra can be expelled by contractions of the bulbocavernosus muscles.

These different arrangements mean that men and women develop different pathologies.

Question 8

Generally, describe the bladder innervation.

Answer 8

Micturition is a process by which the neural circuits of the brain and spinal cord coordinate the activity of the smooth muscle in the bladder and urethra. These circuits act as on/off switches to alternate the lower urinary tract between the two modes of operation: storage and elimination.

It is important to understand these because any injury or disease of the nervous system in adults can disrupt the voluntary control of micturition and cause the re-emergence of reflex micturition, which results in bladder hyperactivity and urge incontinence.

The lower urinary tract is innervated by 3 sets of peripheral nerves involving the parasympathetic, sympathetic and somatic nervous systems.

Question 9

What are the two types of bladder innervation?

Answer 9

Bladder innervation is:
SENSORY: gives sensation (awareness) of fullness, and also pain from disease

MOTOR: causes contraction and relaxation of the detrusor muscle and the external sphincter to control micturition

Question 10

Describe the motor innervation of the bladder.

Answer 10

The parasympathetic arises in the ventral/anterior horn at the sacral region of the spinal cord, and the preganglionic fibres synapse onto postganglionic fibres on the wall of the bladder and internal sphincter.

The sympathetic arises in the lateral/ posterior horn at the lumbar region of the spinal cord. It follows a complex route and the preganglionic fibres synapse onto the postganglionic neurones in the hypogastric ganglia. Some postganglionic neurones supply the internal sphincter, while others innervate with the parasympathetic ganglia in the bladder wall (inhibiting transmission). A few sympathetic neurones actually end in the detrusor muscle; more are found in the trigone area.

The somatic also arises from the sacral region of the spinal cord and supply the striated muscle of the external sphincter.

Question 11

Describe the innervation of the detrusor muscle.

Answer 11

The main parasympathetic transmitter is acetylcholine, but it also releases ATP. Acetylcholine is much more important because atropine (muscarinic agonist) inhibit detrusor contraction.

The sympathetic transmitter is noradrenaline which acts on α-receptors to inhibit transmission at the parasympathetic ganglion. Some relaxation of the bladder body is caused by the direct release of noradrenaline acting on β-receptors (usually in the trigone area).
It is thought to be more important during ejaculation in men, whereby it acts to relax the bladder and close the internal sphincter to stop semen entering the bladder.

Question 12

Describe the innervation of the sphincters.

Answer 12

The parasympathetic nerves release nitric oxide to act on muscarinic receptors, which relaxes the internal sphincter.

The sympathetic nerves release noradrenaline to act on the α1-receptors, which contracts the internal sphincter.

The somatic nerves release acetylcholine, which acts on nicotinic receptors, which, with tonic (continual) activity, holds the external sphincter closed.

Question 13

Describe the sensory innervation of the bladder.

Answer 13

The pelvic, hypogastric and pudendal nerves contain afferent axons that transmit information from the lower urinary tract to the lumbosacral spinal cord.

The main afferent pathway is via the pelvic nerve (parasympathetic). There are small myelinated Aδ–fibres, which cause a micturition reflex; they have stretch receptors to signal wall tension, and volume receptors to signal bladder filling. There are also unmyelinated C fibres with ending in or near the epithelium, they are nociceptors for pain (eg. during an infection of the bladder lining, such as cystitis, excessive distension, etc.).

There are also the hypogastric (sympathetic) and pudendal (somatic) pathways. They involve nociceptors and flow receptors (on the external sphincter).

Question 14

With afferent (sensory) nerves, what is the difference between A and C fibres?

Answer 14

A FIBRES: sense tension in the detrusor:

• filling of the bladder
• detrusor contraction
• bladder fullness, discomfort

C FIBRES: respond to damage and inflammatory mediators.
- PAIN as an urgent desire to micturate

Question 15

Describe the changes in the bladder nerve stimulation when its being filled.

Answer 15

Initially, the bladder is empty. The sphincters are closed (due to the tonic activity from the sympathetic and somatic nerves). The bladder pressure is low.

With the arrival of urine, the detrusor muscle begins to relax progressively (as the sympathetic activity is inhibiting the parasympathetic transmission). There is a little increase in pressure, though the sphincters are still closed.

Question 16

What is receptive relaxation?

Answer 16

It is the phenomenon of a hollow organ relaxing as it fills (as seen in the bladder and stomach).

Question 17

How do we feel the bladder filling and its pressure?

Answer 17

We first become conscious of the bladder filling when there’s 100-150 ml of urine in the bladder. Above this volume, the sensation becomes more distinct till discomfort begins between 300-400 ml. Further distension beyond this causes mounting distress and, eventually, frank pain.

The threshold volume differs from person to person.

Question 18

Describe the changes in the bladder nerves activity during the micturition (emptying) reflex.

Answer 18

Receptors detect tension in the bladder wall - afferent activity is excited - this triggers activity in the parasympathetic efferents which supply the detrusor and internal sphincter by the spinal reflex arc. The detrusor muscle contracts due to acetylcholine, and it is reinforced by ATP. Other parasympathetic fibres relax the internal sphincter (with acetylcholine and nitric oxide) and urine flows out.
The entry of the urine into the first part of the urethra triggers the afferent nerves. These reinforce micturition by inhibiting the somatic nerves which tonically contract the external sphincter.

So, by now, the detrusor muscle is contracting, both the internal and external sphincters are relaxed and urine flow is established. These all depend on the sacral reflex.

NOTE: The continued positive feedback from the tension receptors in the bladder walls and urine in the urethra all reinforce micturition until the bladder is empty.

Question 19

How can the micturition reflex be modified by higher centres?

Answer 19

After looking at the activation pattern during micturition superimposed on averaged MRI scans, we can conclude that a widespread involvement of the cortical and subcortical areas is disclosed in accordance with clinical and animal studies.

Many neuron populations are involved, including the specific pontine micturition centre (PMC).

Question 20

Describe the voluntary modification of the micturition reflex.

Answer 20

Higher centres can modify the micturition reflex for a while:

• you can contract the external sphincter and levator muscle consciously
• you can increase the sympathetic firing to the bladder and the internal sphincter (not directly, but it is thought that maybe due to the contraction of the levator and external sphincter muscles, the urethra compresses and this allows the increase in sympathetic firing)
• (following the one above) it interferes with the positive feedback to the bladder emptying by the inhibition of parasympathetic transmission and tightens the internal sphincter.
• the urine stream can be halted by ‘strangury’ (urethral pain) due to urethritis (the inflammation of the urethra from an STI or renal calculi)
• pinching the glans penis can inhibit micturition
• at night, if the bladder fills to capacity, it is recognised by the PMC and the arousal centre wakes you up

Question 21

Describe the normal control of micturition.

Answer 21

To stop the micturition message from reaching the micturition inhibitory centre in the frontal lobe and the micturition centre in the pons, we increase sympathetic activity to block parasympathetic activity and hence keep the bladder relaxed and the internal sphincter closed. So, in essense, to allow the voluntary release of urine, the pons and cerebrum quieten the sympathetic input into the bladder and allow the parasympathetic system to take over (as in the reflex).

This is usually brought about by contracting abdominal muscles which increase the pressure in the bladder. Hence, the urine enters the bladder neck and the urethra under pressure, stimulating stretch receptors in the wall, which excite the micturition reflex as described.

Question 22

What is the importance of the bladder emptying?

Answer 22

The main function is to release the urine in the bladder.
Urine is normally sterile, however, there is the occasional bacterial entry. Complete emptying restores sterility. Ordinarily, all the urine is emptied, with rarely more than 5-10 ml left in the bladder. The bacteria in the retained urine seeds fresh urine.

Retained urine can lead to a clinical infection (UTI). Repeated infections can destroy renal function if they ascend to the kidney.

Question 23

Describe UTIs (urinary tract infections.

Answer 23

A urinary tract infection is an infection that can happen anywhere along the urinary tract. UTIs have different names depending on what part of the urinary tract is infected.

They are more common in women as they have a shorter urethra. They are also common in men over 40 due to prostatic disease, causing bladder outflow obstruction.

Some risk factors:

• diabetes mellitus
• long-term catheterisation
• pregnancy
• enlarged prostate
• prolonged immobility
• kidney stones
• bowel incontinence
• advanced age

Question 24

UTIs have different names depending on what part of the urinary tract is infected.

Elaborate.

Answer 24

BLADDER: an infection in the bladder is also called CYSTITIS or a bladder infection

KIDNEYS: an infection of one/both kidneys is called PYELONEPHRITIS

URETERS: rarely a site of infection

URETHRA: an infection of the urethra is called URETHRITIS

Question 25

What are some problems associated with an aging bladder?

Answer 25

They will have a slow urine stream. This is commonly due to prostate enlargement (BPH - benign prostatic hyperplasia); it is the most common cause of lower urinary tract symptoms in men (occurring in 25% of men >40 years).

As a consequence of a slow urine stream, we have incomplete emptying of the bladder, which could lead to an infection.

The sphincters will also weaken with age. If the sphincters weaken, then even normal bodily functions such as coughing, stooping or laughing raises bladder pressure sufficiently enough to squeeze urine past them - this is frequently seen in women who’ve had many children. It is socially very embarrassing and distressing.

In people with an overactive bladder (OAB), the layered, smooth muscle that surrounds the bladder (detrusor muscle) contracts spastically, sometimes without a known cause, which results in sustained, high bladder pressure and the urgent need to urinate. People with OAB often experience urgency at inconvenient and unpredictable times and sometimes lose control before reaching the toilet (urge incontinence). Thus, an overactive bladder interferes with work, daily routine, intimacy and sexual function. It causes embarassment, and can diminish self-esteem and quality of life.

Question 26

Describe stress urinary incontinence.

Answer 26

Normally, increased intra-abdominal pressure forces the urethra against the intact pubocervical fascia, closing the urethra and maintaining continence.

With stress urinary incontinence, defective fascial support allows posterior rotation of the UV junction due to the increased pressure, opening the urethra and causing urine loss. The ureterovesical junction (UV junction) is located where the ureter (the tube that drains urine from the kidney) meets the bladder.

Question 27

How would we treat incontinence?

Answer 27

• These medications are antimuscarinics, which affect the central nervous system and muscarinic receptors in smooth muscle. They relax the smooth muscle of the bladder, reducing detrusor contraction and subsequent wetting accidents, usually within two weeks. Side effects such as dry mouth, constipation, headache, blurred vision, dry eyes, hypertension, drowsiness and urinary retention occur in approximately 50% of those who use these medications. These should be used with caution in patients with narrow-angle glaucoma or certain types of kidney, liver and urinary problems.
• Kegel exercises can also be used for bladder retraining (used for stress and urge incontinence). You ‘squeeze’ your pelvic flow muscles (as if trying to stop urine flow) for 10 seconds, then rest for 10 seconds. Doing this 10 to 20 times a day for several weeks can make a huge difference.
• There are different types of surgery for incontinence, including: bladder neck suspension or sling, collagen injections around the urethra, implantation of an artificial urinary sphincter, tension-free vaginal tape (TVT). Also, Botox is injected into the sides of the bladder to treat urge continence and OAB; it relaxes the bladder and lasts for several months before repeat injections are needed.
• In sacral nerve stimulation, an electrical current is applied to the sacral nerve, supplying the lower urinary tract via an implanted pulse generator. It provides complete continence in 50% of patients and improvements in 80% of patients with urge incontinence. It works better in women than in men.
• Stem cell therapy is also available, where cultured stem cells are inserted into the bladder wall. 90% of people found that there was no leakage; however, it was limited by the supply of stem cells (bone marrow).
• We could also get a tissue engineered bladder. Synthetic and natural scaffolds are used to form a 3D structure using human tissues. It is currently in Phase II trials.