Gastrointestinal tract motility Flashcards
The GI tract is composed of the same 4 layers along its length.
- Name these 4 layers
- What layers contain the enteric nervous system.
1- Mucosa
- epithelium
- lamina propria
- muscularis mucosa
2- Submucosa
- Submucosal plexus
3- Muscularis externa
- Myenteric plexus (located between CM and LM) - responsible for peristalsis
4- Serosa
Describe the structure of Smooth muscle which is found along GI tract.
- How does it structure relate to its function?
-
Dense bodies act as attachment points for cytoskeletal proteins at points through the cell membrane.
> Actin and myosin filaments overlap between dense bodies. - Intermediate filaments such as desmin lie between dense bodies and act to scaffold the interaction of the thick and thin filaments.
- No T-tubules and poorly developed sarcoplasmic reticulum.
-
Latch bridges
> Specialised for long-term, maintained contraction using limited amounts of ATP.
What is the difference between smooth muscle and skeletal muscle?
Smooth muscle is not striated and involves more long term contraction maintained with limited ATP whereas striated muscle is more short term powerful contractions with high ATP use
What are the differences between the two types of smooth muscle and the need for both?
- Multi-Unit
- Individual fibres
- Stimulated independently
- Fine contractions
- Unitary
- Bundles of tissue
- Connected by gap junctions
- Contract as single unit
- Coordinated contractions in circumference and specific direction eg GI tube
What is ATPase activity?
- Ability of myosin to hydrolyze ATP to release energy for muscle contraction.
Describe the process of smooth muscle contraction.
1- Intracellular [Ca2+] increase when Ca2+ enters cell from ECF or SR
2- Ca2+ binds to Calmodulin.
3- Ca2+/ Calmodulin complex activates myosin light chain kinase (MLCK)
4- MLCK phosphorylates myosin light chains in myosin heads → increasing myosin ATPase activity (hydrolysis of ATP)
5- Phosphorylated myosin binds with actin forming cross-bridges
6- Actin slide along myosin → contraction
How is smooth muscle contraction regulated by 2 regulatory proteins?
- Low Ca2+ → Caldesmon
binds to tropomyosin & actin blocking myosin-actin binding
(Ca2+/Calmodulin complex is needed to bind to Caldesmon and Calponin to unlock the binding sites on actin)
Describe the process of smooth muscle relaxation.
1- Calcium is pumped out cell or moved to intracellular stores (SR)
2- ↓ MLCK activity
3- Dephosphorylation of myosin light chain by myosin phosphatase (not calcium dependent)
4- Crossbridge formation prevented
5- Muscle relation
What are the ways smooth muscle increases intracellular Ca2+?
1- Electrochemical - membrane depolarisation → opening of voltage-gated Ca2+ channels
2- Pharmacomechanical -
- Binding of endocrine messenger to receptor activates Gq protein coupled receptor
- DAG and IP3 (by PLC) produced
- DAG activates receptor activated Ca2+ channel
- IP3 binds to intracellular IP3 receptor on sarcoplasmic reticulum = Ca2+ release from SR
3- IF SR Ca2+ STORES ARE DEPLETED….
- SR Ca2+ sensor (STIM1) usually bound to Ca2+ undergoes a conformational change
- Binds to Store operated Ca2+ channel (Orai1) on plasma membrane → Ca2+ moves into the cell
Calcium decrease in cystol can lead to 2 states which are?
1- Caldesmon and calponin are no longer bound to Ca2+ and bind to actin binding sites → block crossbridge cycling = NO TENSION/CONTRACTION
- Latch Bridge State = MAINTAINS SOME CONTRACTION/TENSION IN ATP DEFICIT
Describe how the latch bridge state is brought about.
1- MLCP (phosphatase) dephosphorylates the phosphorylated myosin light chains whilst still bound to actin
2- Decreases ATPase activity of phosphorylated Myosin light chain → prevents hydrolysis of ATP necessary for detachment of myosin to actin
3- Myosin is bound to actin for longer in each crossbridge cycle until ATP hydrolysis for another cycle
What is Ca2+ independent smooth muscle contraction?
-
Protein Kinase C Activated by DAG
-> Activates MLCK and inhibits MLCP so the proportion of phosphorylated myosin light chains is greater
-> sensitises the cell to contraction as the ATPase activity is greater by more phosphorylated myosin light chains = more crossbridge cycling
What is the enteric nervous system?
- Works independently of any other control system to elicit local reflexes
→ Myenteric plexus – controls GI motility
→ Submucosal plexus – controls both GI motility and secretion - CNS can also elicit effects on GIT indirectly through its stimulation of the ENS.
How does the autonomic nervous system affect GIT.
-> ANS increases or decreases the likelihood of threshold being reached for action potential in ENS
- Parasympathetic – Promotes Motility/secretion
- Sympathetic – Inhibits Motility/secretion and contracts sphincters
The rate of passage through the gastrointestinal tract can be controlled by:(2)
- Contraction of sphincters
- Changing the rate of peristalsis
Coordination of the motility of the GIT as a whole is achieved by long-range neural reflexes where activity in one segments affects the motility in others.
These include the: (5)
1- Gastroileal reflex – Stomach activity promotes the opening of the ileocaecal sphincter.
2- **Colonoileal reflex **- Inhibits ileal emptying when the colon is stretched.
3- Gastrocolic/Duodenocolic reflexes- Food entering the stomach or duodenum promotes the motility of the colon.
4- Enterogastric reflex - Distension of the small and large intestines inhibits stomach motility and secretion.
5- Intestinointestinal reflex – over distension of one part of the intestine leads to relaxation of the rest of the intestine.
Describe the 3 phases of deglutition.
-
Oral phase - Voluntary
Food is chewed/lubricated with saliva to form a bolus. > Tongue pushes bolus to back of mouth.
= Triggers somatosensory receptors which via the medullary swallowing centre triggers a reflex closure of the upper oesophageal sphincter. -
Pharyngeal phase - Involuntary
Propels food from pharynx into esophagus. Soft palate is raised to stop the bolus entering the nasopharynx. Epiglottis contracts to block larynx and prevent aspiration into the trachea. Upper esophageal sphincter opens and allow food to enter the esophagus. -
Esophageal Phase - Involuntary
Bolus is propelled from the pharynx into the esophagus.
Upper esophageal sphincter contracts to prevent reflux. A primary peristaltic wave propels the food bolus from the esophagus into the stomach. If this is not effective a secondary peristaltic wave can be initiated to clear the food.
Peristalsis is an intrinsic local reflex. What muscles are contracting/relaxing in this process?
Remember that ACh + Substance P produce contraction at excitatory neurone, whereas NO + VIP produce relaxation at inhibitory neurone
Describe the process of peristalsis.
- Food causes distension and leads to sheer stress of mucosal cells
- Epithelial cells release 5-HT serotonin
- Activates Intrinsic Primary Afferent Neuron (IPAN)
-> Releases ACh at synapse with excitatory motor neuron
1. Excitatory neuron releases ACh and Substance P
2. Causes contraction of CM at oral end
-> Releases ACh/5-HT at inhibitory motor neuron
1. Inhibitory neuron releases NO and vasoactive intestinal peptide (VIP)
2. Causes relaxation of CM at anal end which decreases resistance to downstream movement
What is Hirschsprung disease?
-
Severe constipation > congenital megacolon
> Characterized by an absence of the ENS in the distal colon (no migration of neurons of the myenteric plexus into rectum).
> The involved segment exhibits increased tone, has a very narrow lumen, and is devoid of propulsive activity.
> As a result, the colon proximal to the diseased segment becomes dilated, thus producing a megacolon. - This condition is treated through surgical removal of the diseased segment.
Slow wave frequency varies through the GI tract:
Small intestine - 10 to 20 times/minute
Stomach & large intestine - 3 to 8 times/minute
- What are slow waves and how are they generated?
- Cyclical changes in membrane potential on GIT smooth muscle
- Waves of partial depolarization in smooth muscle sweep along the digestive tube for long distances
- Resting membrane potential = -50/-60 BUT spontaneous fluctuations by 5/15mv spread to adjacent sections of smooth muscle, giving rise to the “slow waves.”
- Prepare the smooth muscle cells contractions by controlling the appearance of “spike potentials,” which are a type of depolarisation event that can lead to muscle contractions. Slow waves set the basic rhythm of smooth muscle contractions.
-> Generated by pacemaker cells - Interstitial cells of Cajal (ICC)
How do we get from the bolus distending the gut and stretching walls to contraction?
-COORDINATED MUSCLE CONTRACTIONS
How can slow waves be modulated by other inputs to trigger contractions?
- The modulation of slow waves in the GI tract involves the integration of various inputs, including neural, hormonal, mechanical, and chemical factors. These inputs can influence the activity of ICCs and smooth muscle cells, adjusting the timing and strength of contractions to optimize the digestive process.
> Tonic (continuous) slow waves + ANS or endocrine input = Phasic (in phases) contraction
Describe the process of the Migrating motor complex.
- ENS signals initiate onset of MMC (fasting)
-> Phase 1: Quiescence
GIT tract has minimal or no contractile activity.= resting period before the initiation of the MMC cycle
-> Phase 2: Phase II: Initiation
Activation of the ENS leads to the onset of irregular, Low amplitude contractions.
(Gradually increase in frequency & amplitude, preparing for the upcoming active phase.)
-> Phase III: Active phase
Characterized by Intense coordinated contractions.
Stomach → terminal ileum.
= Propel luminal contents forward, clearing out residual material, bacteria, and debris.
* Thought to be elicited by motilin – amino acid peptide released from M cells in the duodenum.
What is Achalasia + Causes?
Treatment?
- A failure of esophageal peristalsis and relaxation of the lower esophageal sphincter in response to swallowing.
> Caused by the loss of the VIP and nitric oxide-releasing inhibitory interneurons in the myenteric plexus. Excitatory neural tone dominates preventing LES relaxation.
- Possibly an autoimmune disease as activated cytotoxic T-cell infiltration has been observed in patients, as well as antibodies to myenteric neurons.
Heller myotomy, botulinum toxin & endoscopic pneumatic dilatation.
What is the gastric accommodation reflex? What is its function?
- Reflex that allows stomach to relax and increase compliance to accommodate food volume.
- Mediated by vagovagal reflex pathway that activates inhibitory motor neurons in the gastric wall to release nitric oxide and vasoactive intestinal polypeptide VIP
FUNCTIONS:
1- Prevents pressure rising in the stomach
2- Provides time to allow efficient mixing & breakdown of food & controlled release of chyme into the duodenum
3- Allows stomach to be a temporary food store
Explain the process of the gastric accommodation reflex.
Describe how we get churning in the stomach.
1- Slow waves generate peristaltic contractions starting in body → antrum (propels food to antrum & pyloric sphincter)
2- At pylorus, the slow wave triggers pyloric sphincter contraction –preventing chyme release into duodenum
>A stronger wave follows behind which helps grind food up against itself into smaller pieces
3- Increased pressure in antrum pushes stomach contents back towards body (called retropulsion) → grinding motion to break up large food particles → creates liquid chyme to release into the duodenum
4- Liquid chyme slowly released in resting phases between contractions
> Particles <2mm pass through pyloric sphincter
> Remaining large particles cleared by MMC
What role do the:
- Vomiting centre
- Area Postrema
- Nucleus of the solitary tract
have in emesis?
- Vomiting centre (VC), in the medulla oblongata, is the main site of neural control of vomiting.
= receives signals from other centres (e.g. CTZ) & coordinates output - The area postrema (anti-emetic target) includes a chemoreceptor trigger zone (CTZ) (outside BBB), which allow chemical changes in bloodstream to induce feelings of nausea & triggers vomiting
- Nucleus of the solitary tract plays critical role in the initiation & integration of a wide variety of reflexes (e.g. GIT motility)
Describe the 3 phases of emesis.
What is segmentation? What brings them about?
- Segmentation plays a role in mixing the contents of the small & large intestines.
- Different regions of the circular muscle of the gut contract to pinch off lengths of gut contents.
- As one set of contractions end, the next begins but with contractions in different places. This helps mix the contents of the GI tract with digestive secretions and bring them into close contact with the mucosa.
*Elicited by slow waves – a series of waves creates phasic contractions that allow these pinching events to occur at relatively regular intervals
What is haustration of the colon?
- Mixing
- Like segmentation but larger segments
- Motor events in proximal colon
- Contractions of circular muscles create pockets (haustra)
What is mass movement of the colon?
What triggers this?
- Propulsion
- Enhanced rate of peristalsis
- Motor events in distal colon
- Strong contractions preceded by disappearance of haustra and relaxation of circular muscle to facilitate rapid movement of colonic contents for up to 30 minutes
Gastrocolic and duodenocolic reflexes trigger mass movements – triggers faster peristalsis to help empty colon to accommodate new food
