Motility I week 1 Flashcards
Describe the excitation-contraction coupling process of smooth muscle.
electromechanical coupling
pharmacomechanical coupling
Electromechanical coupling: Contractions are triggered by membrane depolarization and action potentials (APs) that travel from cell to cell through gap junctions.
Pharmacomechanical coupling: Contractions occur in the absence of action potentials e.g. in response to neurotransmitter or hormones.
both are equally important in force production.
What is resting membrane potential for intestinal smooth muscle?
What are slow waves (aka basic electrical rhythm)? How/where are they produced? How are they modulated?
Slow waves: electrical control activity of the GI tract): low frequency (3/min stomach; 11-13/min duodenum) wave like oscillations of the membrane potential. Generation of slow waves is autonomous (i.e. neuronal input not required, autonomous smooth muscle function).
Pacemaker activity: Thin layer of interstitial cells (interstitial cells of Cajal) between circular and longitudinal cell layer. The interstitial cells of Cajal generate the slow waves
which are conducted to the neighboring smooth muscle cells via gap junctions.
Modulation of slow waves by enteric neurons: Excitatory motoneurons (ACh, Substance P), increase the amplitude, frequency and duration of the plateau phase of the slow waves.
How do APs modify intestinal smooth muscle contraction? How long do APs typically last?
Action potentials: when slow-waves reach electrical threshold typically a burst of action potentials (APs) is triggered. APs last 10-20 ms. APs enhance contractions.
Describe how smooth muscle cells develop tone and how APs influence muscle tone.
What is baseline tension at membrane potentials more negative than electrical threshold?
Contraction begins when depolarizing phase reaches mechanical threshold. Development of muscle tone and contraction correlate with the degree of depolarization and can occur in the absence of APs. Baseline tension at membrane potentials more negative than electrical threshold is ‘non-zero’ (constant basal tone).
tonic contraction
phasic contraction
Define motility and the two types that occur in the GI tract.
motility: muscular contractions that mix and move the contents of the gastro-intestinal tract to the appropriate sites of digestion and absorption (normally orthograde propulsion; retrograde propulsion occurs, e.g. vomiting)
Functions of GI motility:
propulsion
mixing
reservoir
Give definitions/reasons for each.
Propulsion: controlled transport of mixture of ingested foords, liquids, and GI secretions to the appropriate sites of digestion, absorption, and elimination
Mixing: decreases particle size of ingested foods and provides optimal contact with digestive juices and digestive enzymes
Reservoir: sections of the GI tract serve as reservoirs (stomach, colon) to allow sufficient time for digestive and absorptive tasks of the GI system
Define the following types of motility and state where they occur in the GI tract.
propulsive peristalsis
reverse peristalsis (antipropulsion)
mass movements
segmentation
haustration
propulsive peristalsis:
- esophagus
- lower 2 thirds of stomach
- small intestine
- large intestine
- rectum
reverse peristalsis (antipropulsion): prolongs time that contents are in that compartment to allow for absorption. water is reabsorbed in the colon
- proximal colon
mass movements: large perstaltic waves that travel over long distances
- ascending, transverse, and descending colon
segmentation: local contractile activity that primarily serves the purpose of mixing contents - small intestine
haustration: same as segmentation, use this word for same activity in large intestine - acending, transverse, and descending colon
In the oral cavity, chewing (mastication) of food occurs. List 3 purposes of chewing and how it is generally regulated.
Describe the swallowing reflex and what occurs at each of the listed phases:
oral/voluntary phase
pharyngeal phase
esophageal phase
What type of reflex is swallowing? (long or short range)
Swallowing reflex = sequence of events that result in propulsion of food from the mouth to the stomach. It is a long-range reflex.
1. Oral/voluntary phase: food bolus is moved to pharynx by tongue –> stimulation of tactile receptors (afferent limb of swallowing reflex; initiation of motor impulses to musculature of pharynx and upper esophagus from ‘swallowing center’ in medulla and pons via cranial nerves)
2. Pharyngeal phase (approx. 1 second duration): upwards movement of soft palate (prevents reflux of food into nasopharynx) –> pulling together of vocal cords and movement of epiglottis to cover larynx (prevents food entry into trachea) –>relaxation of upper esophageal sphincter –> initiation of peristaltic wave.
Respiration is reflexly inhibited.
3. Esophageal phase: mainly controlled by swallowing center. Primary peristaltic wave: 3-5 cm/sec –> bolus reaches stomach in 5-10 seconds.
What is the function of the esophagus? What kind of muscle is found in the upper third, middle third, and lower third of the esophagus?
esophagus: Tubular conduit (about 20 cm long) for food transport from mouth to stomach.
Structural aspects:
• Upper third of the esophagus: circular and longitudinal muscle layers are striated
• Middle third: coexistence of skeletal and smooth muscle
• Lower third: smooth muscle
Describe the afferent and efferent innervation of the esophagus in both the striated and smooth muscle parts.
What nerve supplies efferent innervation to the esophagus?
What types of synapses and NTs are involved?
What is the function of the upper esophageal sphincter (UES)?
prevents entry of air into the esopagus
What is the function of the lower esophageal sphincter (LES)? Is the resting pressure positive or negative?
What regulates the tone of the LES?
Describe the control (nerves, NTs, hormones) of contraction and relaxation of the LES.
Lower esophageal sphincter (LES): LES = zone of elevated resting pressure (~ 30 mm Hg) prevents reflux of corrosive acidic stomach content. LES tone is regulated by nerves, hormones and neuromodulators
- *Contraction**: vagal cholinergic nerves (nicotinic, i.e. atropine insensitive) and sympathetic nerves (α-adrenergic). the nicotinic receptors is an exception! typically excitatory synapses on GI smooth muscle are muscarinic.
- *Relaxation**: primary peristalsis –> inhibitory vagal nerve input to circular muscle of LES neurotransmitters (VIP and NO) and reduced activity of vagal excitatory fibers (cholinergic, nicotinic). see attached figure (slide 31 of notes)
Describe the neural circuit (local and central) of the control of esophageal motility.
Describe the pressure profiles of the pharynx, UES, esophagus, and LES during swallowing.
At rest, esophageal pressure is btwn -6 and -1 mmHg. What would be the consequence of having this negative pressure if the LES malfunctioned?
Negative pressure with a sphincter that doesn’t close properly-food goes back from the stomach into the esophagus
What is a secondary peristaltic wave? What is the law of intestine? Describe the NTs involved.
What type of reflex is the law of intestine? (long or short range)
In the event that the bolus gets stuck or moves slower than the primary peristaltic wave (as can happen when it is poorly lubricated), stretch receptors in the esophageal lining are stimulated and a local reflex response causes a secondary peristaltic wave, forcing it further down the esophagus until the bolus enters the stomach.
The secondary peristaltic wave is an example of a local or short intrinsic reflex: Sensory inputs (e.g. mechanical deformation of the intestinal wall, chemical stimuli such as changes of pH) are integrated in myenteric ganglia and efferent fibers to muscle, gland and epithelial cells are activated. Stretching a segment of the GI tract is sensed by sensory enteric neurons. This signal is transmitted via excitatory and inhibitory interneurons to excitatory (proximal) (ACh, Substance P released) and inhibitory (distal) (VIP, NO released) motor neurons, causing ascending excitation and descending inhibition of smooth muscle cells. As a consequence GI content is transported in aboral direction (”law of intestine”). see slide 40 of notes
Describe the following disorders:
achalasia
diffuse esophageal spasms
sclerodermia
gastroesophageal reflux disease (GERD)
hiatal hernia
Achalasia: neurogenic disorder with impairment of esophageal peristalsis and failure of LES to relax and open appropriately
Diffuse esophageal spasms: neurogenic disorder with painful contractions of lower esophagus, loss of normal peristalsis and reflux esophagitis
Sclerodermia: replacement of smooth muscle with fibrous tissue and nerve degeneration. can cause difficulty swallowing
GERD: leaking of stomach contents into the esophagus due to issues with the LES
Hiatal hernia: Protrusion of the stomach above the diaphragm
What are some complications of a hiatal hernia? How is it typically treated?
A hiatal hernia causes backflow of fluid into the esophagus. Because the stomach has protruded through the diaphragm, the diaphragm can no longer help with closure of the LES. Pts can also have difficulty breathing and heart issues because the hernia may displace the heart. Typically requires surgical repair-narrowing of the passage through the diaphragm.
