GI motility

Question 1

What is the structure of the GI tract wall?

Answer 1

Mucosal layer - epithelium, lamina propria (CT), muscularis mucosae
Submucosal layer - collagen, elastin, glands, blood vessels
Muscularis mucosae - smooth muscle cells - oblique, circular, longitudinal
Serosa

Question 2

Smooth muscle in the GI tract

Answer 2

• Non-striated muscle cells type - not orderly arranged in sarcomeres
• Actin = thin filaments
• Myosin = thick filaments
• Intermediate filaments (desmin and dense bodies) anchor points for contractile filaments
• Specialised for long term contraction using little ATP

Question 3

What is the basic mechanism for Ca2+ dependent smooth muscle contraction?

Answer 3

Ca2+ conc in the cytosolic fluid of smooth increases due to influx of calcium
Ca2+ bin reversibly to calmodulin (CaM) = calmodulin-calcium complex
CCM joins and activates myosin light chain kinase (MLCK)
One light chain of each myosin head is phosphorylated in response to myosin kinase
- The head has capability of binding repetitively with the actin filament
- Causes muscle contraction and ATP consumption

Question 4

What is the basic mechanism of Ca2+ dependent smooth muscle relaxation?

Answer 4

When Ca2+ levels fall, kinase becomes inactive, activity of MLCP dominates
Myosin P is dephosphorylated = muscle relaxes

Question 5

Electromechanical coupling

Answer 5

Membrane depolarisation opens the voltage gated Ca2+ channels causing rise in intracellular Ca2+

Question 6

Pharmacomechanical coupling

Answer 6

Ca2+ levels rise from SR and enter via non-voltage gated channels
Chemicals bind to membrane receptors and activate G protein
PLC activation increases concentration of IP3 and DAG - initiates rise in concentration of Ca2+
STIM1 is a Ca2+ sensor that activates store operated Ca2+ channels

Question 7

When may Ca2+ independent contraction occur?

Answer 7

Increase in rate of myosin phosphorylation by MLCK
or
from decrease in rate of myosin dephosphorylation by MLCP

Question 8

What is the latch state hypothesis?

Answer 8

Smooth muscle can maintain high force at low rate of ATP hydrolysis - reduce fatigue
Dephosphorylating myosin already on actin reduces off rate = latch state
Decreased detachment rate increases cross bridge no., lower rate of cross bridge cycling and ATP hydrolysis = low energy consumption/high tension state
After Ca2+ return to normal, smooth muscle retain some tension without spending high ATP

Question 9

Slow waves in smooth muscle

Answer 9

Cyclical changes in membrane potential that underlie phasic contraction and relaxation
originate from interstitial cells of cajal (ICCs) network
Precede events in smooth muscle

Question 10

What are the roles of ICCs?

Answer 10

ICCs (interstitial cells of cajal)
Act as electrical pacemakers
Cells form network through smooth muscle layers
Pacemaker activity cause slow waves which influence depolarisation leading to Ca2+

Question 11

What is the rate of passage through the GI tract controlled by?

Answer 11

Contraction of sphincters
Changing rate of peristalsis

Question 12

What reflexes occur in the GI tract that controls passage of food? (5)

Answer 12

Gastroileal reflex - stomach activity promotes opening of ileocaecal sphincter
Gastrocolic/duodenocolic reflexes - food entering the stomach stomach/duodenum promotes motility of colon
Enterogastric reflex - distension of SI/LI inhibits stomach motility and secretion
Intestinointestinal reflex - over distention of one part of intestine leads to relaxation of the rest of the intestine
Colonoileal reflex - inhibits ileal emptying when colon is stretched

Question 13

What is achalasia?

Answer 13

• Failure of oesophageal peristalsis and relaxation of the LOS in response to swallowing
• Symptoms: dysphagia, chest pain, heart burn, regurgitation
• Caused by loss of vasoactive intestinal polypeptide (VIP) and nitric oxide-releasing inhibitory interneurons in the myenteric plexus
• Excitatory neural tone dominates, preventing LOS relaxation

Question 14

ENS (4)

Answer 14

Enteric nervous system
Myenteric plexus controls GI motility
Submucosal plexus controls both GI motility and secretion
Can work independently to elicit local reflexes -> changes in motility or secretion

Question 15

CNS role in GI tract (3)

Answer 15

CNS can act indirectly on GI via ENS
Parasympathetic - promotes motility/secretion
Sympathetic - inhibits motility/secretion and contracts sphincters
- originates in preganglionic cholinergic neurons
- decrease release of ACh from enteric neurons = inhibits motility/secretion

Question 16

What are the different types of GI peptides? (3)

Answer 16

Hormones: secreted by endocrine cell, portal circulation, liver, systematic circulation, target cell
Paracrines: act locally within same tissue
Neurocrines: released after AP, diffuse across synaptic cleft -> target cell

Question 17

What role does ACh have in the GI system? (5)

Answer 17

• Contraction of smooth muscle in wall
• Relaxation of sphincters
• Increased salivation
• Increased gastric secretion
• Increased pancreatic secretion

Question 18

What are the roles of NE in the GI tract? (3)

Answer 18

• Relaxation of smooth muscle in wall
• Contraction of sphincters
• Increased salivary secretion

Question 19

What are the roles of VIP in the GI tract? (3)

Answer 19

-Relaxation of smooth muscle
- Increased intestinal secretion
- Increased pancreatic secretion

Question 20

What are the role of neuropeptide Y? (2)

Answer 20

• Relaxation of smooth muscle
• Increased intestinal secretion

Question 21

What are the role of peptide YY? (3)

Answer 21

• Decreased gastric H+ secretion
• Decreased pancreatic secretion
• Decreased Ghrelin (decreased appetite)

Question 22

What occurs during receptive relaxation of the stomach? (3)

Answer 22

• Active relaxation of the smooth muscle -> intraluminal pressures fall before bolus arrives
• Relaxation occurs with each swallow, large volumes can be accommodated without rise of intragastric pressure
• After passage of bolus, pressure returns to normal = receptive relaxation

Question 23

What does receptive relaxation of the stomach allow? (2)

Answer 23

• Stomach to be a temporary food store
• Allows time for controlled release of chyme into duodenum

Question 24

How is receptive relaxation mediated? (2)

Answer 24

• Vasovagal reflex - act through serotonin receptors to release NO to cause muscle relaxation
• Mechanoreceptors detect distention > relay to CNS > efferent information to smooth muscle wall of the orad stomach > relaxation

Question 25

What is gastroparesis? (3)

Answer 25

- Delayed gastric emptying without any blockage in the stomach - Symptoms: satiety, bloating, nausea, vomiting - Cause by vagal injury > reduced strength of stomach contraction and failure of pyloric sphincter to effectively relax

Question 26

What is segmentation? Duration? Function? (4)

Answer 26

- Small intestinal motility - non-propagated focal contractions of intestine occurring simultaneously - Different regions of circular muscle of the gut contract to pinch off lengths of contents - Lasts 4-6 hours after eating - Mixes contents of GI with digestive secretions and brings them into contact with the mucosa aswell as contractions of villi and muscularis mucosa

Question 27

What is peristalsis?

Answer 27

- Intrinsic local reflex that moves food through the GI tract towards the anus

Question 28

How peristalsis carried out?

Answer 28

Orchestrated by interstitial cells of Cajal CNS can also elicit effects through stimulation of the ENS - Excitatory neurons cause longitudinal muscle in segment ahead of bolus to contract - Inhibitory neurons cause circular muscles layer to relax in same segment > expansion of lumen - Excitatory neurons cause contraction of circular muscle layer in segment behind bolus - Inhibitory neurons cause relaxation of longitudinal muscle layer in same segment > propulsion of contents

Question 29

What stimulates motor neuron activity in peristalsis? (5)

Answer 29

Luminal distention triggers - direct activation of mechanoreceptive endings of intrinsic primary afferent neurons (IPANs) - Indirect activation of IPANs upon serotonin release from enterochromaffin cells in the epithelium IPANs activate - ascending interneurons > stimulate excitatory motor neurons - descending interneurons > stimulate inhibitory motor neurons Motor neuron activity > propulsion of contents proximal-distal direction

Question 30

What is Hirschsprung's disease?

Answer 30

No migration of neurons of the myenteric plexus into the rectum = faeces become stuck

Question 31

What is the migrating motor complex? (5)

Answer 31

-Cycle of electrical and motor activity that occurs in the fasting state from the stomach down to the terminal ileum - Clears the stomach and SI contents before next meal 3 Phases 1: Quiescence (inactivity) 2: Low grade contractions - ghrelin stimulates and maintains through vagal efferent nerves 3: intense contractions - elicited by motilin, ghrelin also acts on stomach and initiates gastrcic phase 3 contractions

Question 32

What neurological structures are involved to lead to nausea and vomiting? (3)

Answer 32

Stimuli converge on neurons located in emetic centre in medulla Chemoreceptor trigger zone within the area postrema allows chemical changes in blood to induce nausea and vomiting Antiemetics will block the signalling here

Question 33

What stimuli can induce vomiting? (6)

Answer 33

- Pain - Foul odours - Food poisoning - Cancer chemotherapy - Pregnancy sickness - Psychological factors

Question 34

What muscular changes lead to vomiting? (5)

Answer 34

- Retroperistaltic response moves food from duodenum back into the stomach (distension of duodenum, pyloric sphincter and stomach relaxes to accomodate) - Contractions in duodenum and stomach - Contraction of skeletal muscle - abdo wall and downward contraction of diaphragm > squeezes stomach between diaphragm and abdo muscles > forced inspiration - Increased in abdo pressure and decrease in thoracic pressure, propels stomach contents out - Movement of larynx up and forward and relaxation of upper and lower oes sphincter > allows contents from stomach through oes and mouth

Question 35

Describe the movement of contents through the colon (5)

Answer 35

- Entry controlled by ileocecal sphincter continuously - Contents pushed by mass movement under autonomic control (initiated by stimulation of parasympathetic sacral outflow tracts) - Gastrocolic reflex increases colonic motility within 30 min of a meal - neurally mediated by CCK release - Giant peristaltic contraction = peristaltic reflex = high amplitude and long duration contractions - Contents semisolid in distal colon, harder to move, final mass movement propels contents into rectum

Question 36

What is defacation controlled by?

Answer 36

Prevented by tonic contraction of internal and external anal sphincters - Internal = smooth muscle - subconsciously controlled - External = skeletal muscle - voluntarily controlled