Micturition

Question 1

What happens in the ureter?

Answer 1

Urine enters ureter- distends it and smooth muscles around the contract
Peristaltic waves in the ureter occur at a frequency of around 1 to 6 per minute
Ureter squeeze urine to pressure of 10-20mmHg

Question 2

How does urine pass from the ureter to the bladder?

Answer 2

Ureters open obliquely into the bladder,
Prevents reflux of urine back into ureters by passive flap-valve effect- the filling the bladder puts pressure on the ureter closing it
Ureteric peristalsis is myogenic in origin and NOT under CNS control
The coordination required between peristalsis and changing urine volume
The bladder can hold up to 400ml without much increase in pressure-> spherical structure

Question 3

What are the sphincters of the bladder like?

Answer 3

Internal Sphincter:
Extension of detrusor muscle is NOT under voluntary control
External Sphincter:
Two striated muscles (compressor urethrae & bulbocavernosus) surrounding urethra
these muscles are responsible for continence
These muscles are under conscious, voluntary control

Question 4

What are the female bladder and urethra like?

Answer 4

Short urethra - only carries urine
External sphincter less well developed
More prone to incontinence particularly after childbirth.

Question 5

What is the male bladder and urethra like?

Answer 5

The urethra passes through the middle of the prostate gland
Carries urine and semen
Urine elimination aided by contraction of bulbocavernosus muscles in the penis

Question 6

What are the characteristics of the bladder?

Answer 6

Lining – transitional epithelium
Bladder muscle - detrusor
Impermeable to salt & water
Permeable to lipophilic molecules
NB composition of urine does not change in bladder
Outlet of bladder into urethra:
Internal Sphincter – smooth muscle, involuntary control
External Sphincter – striated muscle, voluntary control

Question 7

What are kidney stones?

Answer 7

A most common disorder of urinary tract
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 made up of uric acid (<10%), struvite (<10%), cysteine (<5%).

Question 8

What are kidney stones caused by?

Answer 8

NOT the same as gall stones
More common in men than women (2-3:1) – due to testosterone (Liang et al, 2014, Mol. Endo. 28:1291-1303)
Caused by: 
-excess dietary intake of stone-forming substances
-poor urine output/obstruction
-altered urinary pH
-low concentration of inhibitors
-infection

Question 9

What is ureterolithiasis?

Answer 9

Kidney stones can form anywhere within urinary tract: kidney, ureter or bladder
Symptoms:
Dysuria (painful urination)
Haematuria
Loin pain/back pain
Reduced urine flow
Urinary tract obstruction: pressure reaches 50mmHg - causes considerable pain “renal colic”
If stone approaches tip of urethra – intense pain can inhibit micturition

Question 10

What is staghorn calculus?

Answer 10

Crystals growing within the kidney-like a crystallised plaster cast of the kidney

Question 11

What are the ‘players’ of bladder innervation?

Answer 11

Micturition is governed by the brain and spinal cord
Neural circuits in brain & SC co-ordinate activity of bladder & sphincters
Circuits act as on-off switches to alternate between storage & elimination
We have 3 main branches of nerves each one with an afferent and efferent innervation
Typically what is detected is a stretch in the bladder by the afferent and the efferent controls the bladder muscles
Three branches each correspond to a different type of nervous system
The nerves:
Sympathetic- hypogastric nerve
Parasympathetic - pelvic nerve
Somatic- pudendal nerve

Question 12

What are the types of innervation in the bladder?

Answer 12

Sensory (afferent):
Gives sensation (awareness) of fullness and also pain from disease
Motor (efferent):
Causes contraction and relaxation of detrusor muscle and external sphincter to control micturition

Question 13

What do the motor types of nerves do in the bladder?

Answer 13

Efferent innervation of the bladder
Parasympathetic- pelvic nerve
Sympathetic- hypogastric nerve with hypogastric ganglia
Somatic- pudendal nerve governing the external sphincter

Question 14

How does the efferent innervation of the detrusor work?

Answer 14

We have the parasympathetic nerve, between ganglia Ach is released and that interacts with nicotinic receptors on the post-ganglion
At the neuromuscular junction Ach is released to interact with muscarinic receptors while ATP reacts with purinergic receptors
Ach and ATP cause detrusor muscle to contract, causing the bladder to squeeze
Atropine can inhibit the action of ACh on the muscarinic receptor at the neuromuscular junction inhibiting detrusor contraction
Sympathetic post-ganglion can synapse on the parasympathetic post-ganglion so NA inhibits transmission at parasympathetic ganglia indirectly causing detrusor to relax
Sympathetic nerve will innervate directly on the detrusor muscle causing NA to also directly via b-Rs (also in trigone area) causes detrusor to relax

Question 15

How are the sphincters innervated?

Answer 15

Parasympathetic:
Nitric oxide and Ach are released
Nitric oxide (NO) and Ach relax internal sphincter
Sympathetic:
NA released act on alpha1 receptors
Noradrenaline (NA) contracts internal sphincter
Somatic:
We believe its Ach acting via nicotinic receptors
Tonic (continual) ACh activity holds external sphincter closed

Question 16

(In summary) what does motor innervation do to the bladder?

Answer 16

Encourage micturition
Parasympathetic neurons:
Contract detrusor via ACh (muscarinic R) & ATP (purigenic R)
Relax internal sphincter via  NO (cGMP) & ACh (nicotinic R?)
Inhibit micturition
Sympathetic neurons
Relax detrusor 
indirectly via NA (α-R) 
Directly via NA (β-R)
Contract internal sphincter via NA (α-R)
Somatic neurons:
Contract external sphincter via ACh (nicotinic R)

Question 17

What are the types of afferent (sensory) nerve fibres?

Answer 17

“A fibres”: sense tension in detrusor so detect:
i. Filling of bladder
ii. Detrusor contraction
These are the nerve fibres that detect bladder fullness, discomfort
“C fibres”: respond to damage & inflammatory mediators
⇒Cause PAIN (urgent desire to micturate)

Question 18

What do each of the sensory nerves do?

Answer 18

Main afferent pathway is via pelvic nerve (parasympathetic):
Small myelinated Aδ–fibres ⇒control micturition reflex
They work via stretch receptors ⇒ signal wall tension
They also have volume receptors ⇒ signal bladder filling
Unmyelinated C fibres ⇒ endings in/near epithelium
So they are nociceptors ⇒ pain (e.g. during infection of bladder lining – cystitis; excessive distension)

Hypogastric (sympathetic) & Pudendal (somatic) pathways:
Nociceptors
Flow receptors (external sphincter)

Question 19

How does the bladder fill?

Answer 19

Initially – bladder empty:
Sphincters closed 
Maintained by the tonic activity sympathetic & somatic nerves
Bladder pressure low
Arrival of urine:
Detrusor relaxes progressively - sympathetic activity inhibiting parasympathetic transmission
Little increase in pressure
Sphincters still closed
This is called receptive relaxation

Question 20

How does the bladder empty (micturition)

Answer 20

Micturition is an autonomic reflex
e.g. in babies (<18months), adults with spinal cord transected above sacral region
Reflex is modified by voluntary control
-Inhibited or initiated by higher centres in the brain
-Maturation of bladder complete by >6 years
Basic circuits act as on/off switches to alternate between 2 modes of operation: storage and elimination
Disease/injury/ageing to nervous system in adults disrupts voluntary control of micturition
-bladder hyperactivity & urge incontinence
-stress incontinence

Question 21

How does the micturition reflex occur?

Answer 21

The filling of the bladder will be detected as receptors in the bladder wall “fire off’ with increasing tension, at this stage would be Ad-fibres (afferent) signalling to the spinal cord
This will return via parasympathetic efferent pathway, this will have two effects:
Contraction of detrusor muscles
Relaxation of the internal sphincter
Urine will begin to leave the bladder
The flow of urine will be detected by flow receptors in urethra activating pudendal afferent nerves
Then the tonic contraction of external sphincter is removed by inhibition of somatic input to maximise urine flow
This sacral reflex is important to reinforce micturition till bladder is empty

Question 22

How can the micturition reflex be modified voluntarily?

Answer 22

Higher centres can modify micturition reflex for a while:
Contract external sphincter & levator muscle consciously
Increase sympathetic firing to bladder and internal sphincter (voluntary??)
-Interferes with positive feedback to bladder emptying by inhibition of parasympathetic transmission
-Tightens internal sphincter

Urine stream can be halted by “strangury” (urethral pain) due to urethritis (inflammation of urethra from STI or renal calculi)
Pinching glans of the penis can inhibit micturition
At night, if bladder fills to capacity, recognised by PMC and arousal centre wakes you up

Question 23

How is micturition controlled normally (i.e. the pathway)

Answer 23

The cerebral cortex and frontal lobe as well as the brainstem pons (the micturition inhibitory centres) signal via spinal cord through spinal efferents via the sympathetic pathway to block parasympathetic activity
But as the bladder expands this will be detected by Ad myelinated afferent, which will feed to the spinal tract and registered within the brain stem, and then if unresolved later by the C unmyelinated afferents

Question 24

What is the importance of bladder emptying?

Answer 24

Urine
Normally sterile
Occasional bacterial entry
Complete emptying restores sterility
Bacteria in retained urine seeds fresh urine
Retained urine causes clinical infection (UTI)
Repeated infections can destroy renal function if ascend to kidney

Question 25

Where do UTIs happen?

Answer 25

Can happen anywhere along the urinary tract
UTIs have different names, depending on the area of infection:
Bladder – an infection in the bladder is called cystitis or a bladder infection
Kidneys – an infection of one/both kidneys is called pyelonephritis
Ureters – rarely the site of infection
Urethra – an infection of the urethra is called urethritis

Question 26

What are the UTI risk factors?

Answer 26

More common in women because of short urethra
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 27

What are the problems of an ageing bladder?

Answer 27

Incontinence
Causes:
Weakening of sphincters (e.g. stress incontinence)- common in women after child-birth, weakened pelvic floor muscles
Failure of nervous control
Overactive bladder (OAB) – detrusor contracts spastically – results in sustained high bladder pressure– urge incontinence
Consequences:
Socially embarrassing
Diminishes self-esteem
Reduces quality of life

Question 28

How do you treat bladder problems?

Answer 28

Anti-muscarinics ⇒ relax smooth muscle & ↓ detrusor contraction
(e.g. non-specific muscarinic receptor antagonist Oxybutynin – wide ranging side effects)
Bladder retraining (used for stress & urge incontinence):
Timetable & Kegel exercises
KEGEL exercises:
Clench the muscles you would use to stop the flow of urine.
Hold the squeeze for 10 seconds, then relax.
Do three or four sets every day.
As these muscles grow stronger so will your bladder control.
Surgery:
Bladder neck suspension
botulinum toxin/collagen injections into muscles around urethra → relaxes bladder (OAB)
Sacral Nerve Stimulation (SNS):
implanted neurostimulation system
electrical impulses to sacral nerve
Stem cell therapy potentially in the future:
Frauscher et al (2004) cultured stem cells into bladder wall
⇒ 90% no leakage
Limited by supply of stem cells (bone marrow)
Tissue engineered bladder also in the future:
Synthetic and natural scaffolds to form 3D structure using human tissue.
Currently in phase II trials.