Principles of the Bladder and Micturition Reflex Control

Introduction to Bladder Control and the Micturition Reflex

• This lecture (Lecture 3, Part 1 for MMED 2931) focuses on the physiological control of the bladder and regulation of urine output.

• The central mechanism discussed is the micturition reflex, which involves complex spinal and nerve pathways.

• Reference material includes several textbooks, with specific credit given to the work of Chet De Groat regarding bladder sensory endings.

Anatomical Structures of the Bladder and Urethra

• Ureters: These tubes drain urine from the kidneys into the bladder.

• Detrusor Muscle: The main smooth muscle layer of the bladder wall responsible for contraction during voiding.

• Urethra: The canal through which urine is discharged to the external environment.

• Sphincters:

  • Internal Urethral Sphincter: Composed of smooth muscle.

  • External Urethral Sphincter: Composed of skeletal muscle.

• Innervation: Each component is communicated with by distinct nervous systems (parasympathetic, sympathetic, and somatic) and specific nerves.

Neurotransmitters and Receptor Mechanisms

• The physiological response of the bladder and sphincters is determined by the specific receptors expressed on the muscle tissue, rather than the neurotransmitter itself.

• Acetylcholine (ACh):

  • Released by parasympathetic nerves.

  • Acts on Muscarinic ($M_3$) receptors on the detrusor muscle to cause contraction.

  • Acts on Nicotinic receptors (ligand-gated channels) for fast activation elsewhere.

• Noradrenaline (NA):

  • Released by sympathetic nerves.

  • Acts on $\beta_3$ receptors on the detrusor muscle to cause relaxation (inhibition).

  • Acts on $\alpha$ receptors on the internal urethral sphincter to cause contraction (constriction).

• ATP (Adenosine Triphosphate):

  • Acts as a neurotransmitter released from both sympathetic and parasympathetic pathways.

  • In the bladder detrusor, ATP binds to $P_2X$ receptors (ligand-gated channels) to cause contraction (excitatory).

  • This differs from the gut, where ATP binds to $P_2Y$ receptors to cause relaxation (inhibitory).

• Nitric Oxide (NO):

  • An unusual neurotransmitter that is not stored but produced on demand.

  • Typically inhibitory; it serves to relax the urethra and detrusor muscle.

Physiology of the Filling and Micturition Phases

• Voiding (Micturition): The release of urine to the outside world when socially convenient.

• The Filling Phase:

  • Detrusor Muscle: Must remain relaxed to allow for bladder expansion. To achieve this, parasympathetic nerve activity is inhibited.

  • Internal Urethral Sphincter: Must remained constricted to prevent leakage. This is achieved through activation of the sympathetic nervous system.

  • External Urethral Sphincter: Must remain constricted. This is achieved via the somatic nervous system (pudendal nerve).

• The Micturition (Voiding) Phase:

  • Detrusor Muscle: Stimulated to contract through the activation of the parasympathetic nervous system (releasing Acetylcholine).

  • Sphincters: Both the internal and external sphincters are inhibited/relaxed to allow urine flow.

  • This cycle is essentially the reverse of the filling phase.

Sensory Neural Pathways of the Bladder

• Sensory Neurons: The cell bodies (containing nucleus and DNA) for bladder sensation are located in the Dorsal Root Ganglia (DRG).

• Location of Nerve Endings: There are no nerve cell bodies within the bladder itself. Instead, the bladder contains sensory nerve endings (long axons).

• Mechanism of Activation: These endings are stimulated by distension (stretching of the bladder wall) as it fills with urine.

• Signal Transmission: Once activated, these inputs are sent to the spinal cord and then to the brain to be registered as the urge to void.

• Note: Bladder sensory endings were not definitively identified until the year $2018$.

Motor (Efferent) Neural Pathways

• Sympathetic Nervous System:

  • Originates in the thoracolumbar region of the spinal cord ($T_{10}$ to $L_1$).

  • Neurons are located in prevertebral ganglia outside the spine: the Inferior Mesenteric Ganglia and the Pelvic Ganglia.

  • Releases Noradrenaline and ATP.

• Parasympathetic Nervous System:

  • Originates in the sacral spinal cord ($S_2$ to $S_4$).

  • Preganglionic neurons in the spine synapse onto postganglionic neurons in the Pelvic Ganglia (or Pelvic Plexus).

  • Primarily releases Acetylcholine to contract the detrusor.

• Somatic Nervous System:

  • Controlled voluntarily via the Pudendal Nerve.

  • Innervates the external urethral sphincter (skeletal muscle).

  • Allows the individual to override the micturition reflex when voiding is not socially convenient by keeping the external sphincter constricted.