Micturition

What muscle makes up the wall of the bladder itself?

Detrusor muscle

What tissue composes the internal “sphincter” of the neck of the bladder?

• Smooth muscle and elastic tissue

  • Not a true anatomical sphincter, but stretching of the bladder muscle puts tension at the neck, contracting it and blocking it off

What tissue composes the external sphincter of the bladder/urethra?

skeletal muscle

• True anatomical sphincter

The bladder is under _____, _______ and _________ nervous control.

somatic, parasympathetic, sympathetic

What nerve runs to the external sphincter of the bladder?

Pudendal Nerve

• Containing both somatic sensory and motor nerves

• Acts on the skeletal muscle of external sphincter, giving voluntary control

What sympathetic nerve runs to the smooth muscle (detrusor muscle) of the bladder?

• Hypogastric nerves (Sympathetic nervous system)

  • Sympathetic chain - pre-ganglion fibers make contact with post-ganglionic fibers at level of caudal mesenteric ganglion (Hypogastric nerves)

  • Influence smooth muscle at neck of the bladder (Internal sphincter)

What parasympathetic nerve runs to the smooth muscle (detrusor muscle) of the bladder?

• Long preganglion fibers synapse with short post-ganglion fibers (In end organ)

  • Afferent Fibers - Information into CNS

  • Efferent Fibers - Information out of CNS (Pelvic N.)

Information transmitted from the nerves in the bladder can be integrated in the _____ ______ where ____ ______ of ______ can be sensed.

sensory cortex, pain awareness, distension

What are the three processes the bladder needs to do?

Prevent urine escape (during bladder filling)

Allow urine Storage

Allow micturition-voiding

Describe the physiological mechanisms in place that prevent the escape of urine during bladder filling.

Internal Sphincter

• Tension passively exerted by elastic elements in the neck of the bladder as bladder stretches, brings about blockage of the internal sphincter

• Not true anatomical sphincter (Involuntary control)

External Sphincter

• Stimulate pudendal nerve, which stimulates skeletal muscle in external sphincter, contracts urethalis muscle which prevents urine flow

• True sphincter (voluntary control)

What physiological mechanisms are in place to allow the storage of urine?

• Detrusor must RELAX

• Sphincter must CONTRACT

• Hypogastric Nerve is critical

  • Excitation of sympathetic nervous system causes - relaxation of detrusor muscle (Inhibiting Muscle - inhibitory receptors) and contraction of smooth muscle at internal sphincter (Create contraction - stimulatory receptors)

  • Internal sphincter passively occludes opening at bladder neck

• Pelvic Nerve

  • If bladder is empty, afferent pelvic nerve fibers register low distension at S1-S3. Leads to inhibition of sacral spinal cord reflex by brain relfex center. (Inhibits parasympathetic nervous system)

  • Causes detrusor muscle to relax as bladder fills

Where do the sympathetic nerves innervating the bladder originate in dogs and cats?

L1-4 dogs

L2-5 cats

Where do the parasympathetic nerves innervating the bladder originate in dogs and cats?

Sacral Spinal Segments S1 - S3

What physiological mechanisms are in place to allow micturition or voiding to occur?

• Bladder is distended, causing high activity in afferent fibers triggers the efferent parasympathetic nervous system, this causes contraction of the detrusor muscle of bladder

• Stretch receptors inhibit activity at the hypogastric nerves, which prevent it from relaxing (Allow contraction)

• Stretch receptors also inhibit activity of somatic pudendal nerves, urethral muscle relaxes and urethra opens

What does the voluntary control of the urethra or external sphincter allow for?

• Allows for training, micturition permitted when appropriate, training/behavioral

What causes urinary retention?

Incomplete emptying (or voiding) of urine, with no obstruction of the urinary tract

What may cause urinary retention?

Trauma, pelvic nerve, spinal cord

Spinal disease

Slipped disc in recumbent patients

• No exchange of information between bladder and brain

Chronic bladder distention

Electrolyte disturbances

Neuropathy, midbrain disorders

Dysautonomia

Excessive adrenal steroids (Cushing's disease)

What is urinary incontinence?

Involuntary loss of urine

What are some possible causes of urinary incontinence?

Possible causes:-

• Age

• Spay incontinence (Up to 80% bitches)

• Diabetes

• Kidney disease

• Nerve damage/trauma (local spinal, brain)

• Urinary tract (usually bladder) infections

• Overactive bladder syndrome

• Pressure on the bladder caused by a mass

REMINDER**

• Describe the neurotransmitters and associated receptors for the parasympathetic, sympathetic and somatic nervous system.

Adrenoreceptors all bind _______ or ______ as ___-_____ ______ _____.

• ____ or ____

adrenaline, noradrenaline, G-protein coupled receptors

• Alpha, Beta

a1 adrenoreceptors are ______.

• Which controls what?

stimulatory

• Increase IP3 and DAG → Increased Calcium

• Vasoconstriction of SM (Except in GI)

• i.e. internal urinary sphincter

a2 adrenoreceptors are _______

• Which controls what?

inhibitory

• Decrease adenylyl cyclase → Decreased cAMP

• Presynaptic inhibition, contraction of

B1 adrenoreceptors are ________

• Which controls what?

stimulatory

• Increase adenylyl cyclase → cAMP → Increased PKA → Increased calcium

• Increase cardiac HR, Force, Conduction

B2 adrenoreceptors are ________

inhibitory

• Increase or decrease cAMP

• But cause relaxation of SM (e.g. detrusor bronchodilation, vasodilation in skeletal muscle)

REMINDER**

What can the parasympathetic actylcholine receptors be divided into?

What are the ligand-gated ion channels composed of?

• Pentameric structure

What happens when the nicotinic receptors in the PNS are stimulated?

• What are the three types?

Increase permeability to Nat and K+ (stimulatory)

3 types

• Skeletal muscle, Nu (a1)2ß1,0,8

• Ganglia, Ng (a3)2(4)3 and a3,a5,a7,34, 37

• The brain, NN. (a4)2(B2) 3 and (a7)5

Differentially sensitive to drugs!

Describe the five muscarinic receptors in the PNS.

M1 (neural), ganglia, CNS, gastric parietal cells; activate PLC leading to IP3 and DAG formation, + K+ conductance

M2 (cardiac), all areas of heart, also in the brain stem. Presynaptic inputs to peripheral and central neurones; inhibit adenylate cyclase and open K+ channels inhibiting Ca2+ channels

M3 (glandular/SM), smooth muscle and glandular tissue and the cerebral cortex; activate PLC. Also relaxation of vascular SM, due to NO

M4 (CNS), inhibit adenylate cyclase

M5 (CNS) activate PLC

Green - Stimulatory

Red - Inhibitory

Describe the distribution of muscarinic receptors in the urinary system.

• M3 Receptors (Wall) + M2 Receptors (Wall and neck)

• B2 Receptors (Wall and neck)

• a1 Receptors (Neck of bladder)

Describe the activity of receptors in the bladder during the filling / storage phase.

Sympathetic Dominance

• STIMULATE a1 Receptors at neck of the bladder, contracting smooth muscle at internal sphincter

• STIMULATE B2 Receptors in the detrusor muscle (Leading to relaxation of muscle)

• Inhibits SNS → M2 → Relaxation

Describe the activity of receptors in the bladder during the micturition phase.

Parasympathetic Dominance

• STIMULATE M3 and M2 Receptors

• M3 - Stimulatory, contracts the Detrusor muscle

• M2 - Inhibitory, relax internal sphincter, inhibits SNS

• a1 adrenoceptor - inhibition, allowing sphincter to relax

Under or over activity of receptors in the smooth muscle may cause…

Disorders of storage - Urinary incontinence

• Over-stimulation: Hypercontractile detrusor

• Under-stimulation: Hypocontractile sphincter/urethra

Disorders of storage - Urinary retention

• Over-stimulation: Hypercontractile Sphincter / urethra

• Under-stimulation: Hypocontractile detrusor

Agonists and Antagonists can be ____ and ________.

• Meaning?

specific, nonspecific

• Specific - binds to one type of receptor

• Non-specific - binds to multiple receptors

What are the direct acting agonists and antogonists?

• Agonists - Sympathomimetics, Parasympathomimetics

• Antagonists - Sympatholytics, Parasympatholytics

What are the indirect acting agonists and antogonists?

INDIRECT ACTING

• Sympathomimetics - displace NA

• Parasympathomimetics - ACHEs, displace ACh

What are common causes of situations where the detrusor is hypercontractile or spastic? (Too much voiding)

• What drugs can be used? What is the aim of these drugs?

• Common causes - bladder infections, neurogenic disorders

• AIM: decrease detrusor activity - use antimuscarinic (Decrease M3 stimulation)

• Non specific muscarinic antagonists

  • Oxybutalin, Propantheline, flavoxate, Atropine

What could be some potential issues of giving a non-specific muscarinic antagonist? (As in the case of detrusor hypercontractility).

Side effects reflect the systemic distribution of all muscarinic receptors.

• LOW SALIVA, GI stasis, tachycardia, excitement, sedation, Increase in IOP, mydriasis, antispasmodic effects on GI tract.

What are common causes of destrusor atony? (Too little voiding)

• What drugs can be used? What is the aim of these drugs?

• What side effects might be produced?

Cause - Urinary retention, neurogenic disorders, overdistension

• AIM - increase detrusor activity - cholinergic agonists (M3 Receptors)

• Bethanechol, non specific muscarinic agonists (higher affinity for M3)

• Oral administration of a non-specific drug, still can cause side effects

  • Gl stimulation, hypersalivation, defecation

Which animal is urethral sphincter incontinence common in?

How can it be treated?

What are potential side effects?

• Common in spayed bitches - aetiology not full characterized

• Steroids (Oestradiol) - common treatment, not directly ANS

• AIM - increase sphincter tone - a1 agonists

  • Increase tone - improves continence

• Oral Phenylpropanolamine (non specific alpha adrenergic agonists) and ephedrine (stimulates NA release, less predictable).

• NOTE - systemic distribution, think about where else a1

  adrenoreceptors are located within the body.

  • Hypertension, restlessness, TOP (contraindicated patient groups)

What are common causes urethral spasticity?

• What drugs can be used? What is the aim of these drugs?

• What side effects might be produced?

Cause - Infections, inflammatory neurological disorders, urethral obstruction, Bethanacol treatment

• AIM - decrease sphincter tone - a1 adrenergic antagonist

• Opens internal sphincter, allowing urination to occur

• Can use Phenoxybenzamine (non selective a (a1>a2) IRREVERSIBLE)

  • Can cause: Hypotension, reflex tachycardia, TOP, Gl upset

• Alternatively: Prazosin, terazosin (SELECTIVE a1 antagonist)

  • Can Cause: Hypotension, Gl upset