Gastrointestinal System (Motility) Flashcards
What does the GI tract do?
Th GI tract takes in food, digests it to extract and absorb metabolities for the growth and energy needs of the body plus fluid and electrolytes to replace losses, and expel the remaining waste.
What does the GI system consist of?
A long epitehlium lined tube - with functional secretions seperated by sphincters and connected to accessory exocrine glands.
mouth
pharynx
esophagus
stomach
large intestine
small intestine
anus
What are the three sections of the small intestine?
Duodenum
Jejunum
llium
What are the sphincters of the GI tract?
Upper esophageal sphincter
Lower esophageal spincter
Pyloric sphincter
Sphincter of Oddi (or hepatopancreatic sphincter)
Illeocecal valve
Anal sphincter (internal and external)
What are the salivary glands of the GI tract?
Parotid salivary glands
Sublingial salivary glands
Submandibular salivary glands
What are the accessory exocrine glands of the GI tract?
Salivary glands
Pancreas
Liver
Gall bladder
What are the 4 layers of the GI tract wall?
Mucosal layer
Sub-mucosal layer
Muscularis layer
Serosal layer
What are the two secretoary glands of GI tract wall?
intestinal glands
Submucosal gland
What are the two seperate layers of the muscular layer of GI tract wall?
Circular (inner) and longitudinal (outer) layer
What are the components of the mucosa?
Epithelium
Villi
Lamina Propria
Muscularis mucosae
What are the components of the sub-mucosal layer (the supporting mucosa layer)?
Submucosal plexus, connective tissue blood vessels
What layer of the GI tract wall si the myenteric plexus located in?
Muscularis layer
What is a plexus?
Network of vessels and nerves (layer of neurons)
What is the serosal layer?
The outer sheath of the GI tract wall
What are GI reflexes initiated and senses by?
Stretch = mechanoreceptors
Chemical compositon of luminal contents = osmoreceptors
Concentration of products of digestion in the chyme = chemoreceptors
What is chyme?
Semi-fluid mass of partly digested food
What are the signal pathways of the GI tract?
Neural = CNS and ENS
Hormonal
What are the effectors of the GI tract?
GIT smooth muscle (motility)
Epithelial cells (secretion and absorption of the luminal content)
What are the phases of GI regulation?
1) cephalic phase
2) gastric phase
3) intestinal phase
What is the cephalic phase?
Preparative phase - it prepares the stomach for the arrival of food.
Prepares the GIT lumen by initiating CNS via ENS
What is the cephalic phase stimulated by?
Sensory stimuli: The sight, smell, taste and swallowing of food
Explain how the cephalic phase prepares the stomach:
Inhibits muscles in the proximal stomach (Receptive relaxation)
Triggers low level stimulation of antral contraction by modulation of ENS (antrum = lowest part of the stomach)
Stimulates the release of gastrin from G cells
Starts the regulation of gastric secretion
Is the pyloric sphincter opened or closed during the cephalic phase?
Closed
What is the gastric phase?
The digestive phase in the stomach
What is the gastric phase mediated by?
Mechanoreceptors that responds to the distention by food and chemoreceptors (amino acids and short peptides).
Detects distension, pH and nutrients
Prepares stomach by sending signals ENS, CNS and hormones (gastrin)
Explain how the gastric phase works:
Inhibits muscles in the proximal stomach for gastric accommodation
Stimulates contraction in distal stomach through the release of Ach and Substance P (for retropulsion)
Stimulation of G cell to release gastrin
Is the pyloric sphincter opened or closed during the gastric phase?
Closed
What is the intestinal phase?
The controlled delivery to the duodenum.
Detects stretch, acid osmolarity and nutrient concentrations
Prepares: ENS, CNS, hormones (CCK and secretin)
Explain how the intestinal phase works:
Reduces contraction in the distal stomach > pyloric sphincter periodically opens based on meal composition and size
Does the stomach digest a large or small meal faster?
Large
Does the stomach digest liquids or solids faster?
Liquids
Is high energy food such as fats digested slow or fast?
Slower
Is isosmotic or hyperosmotic food digested faster?
Isosmotic
*Because hyperosmotic needs to undergo osmotic adjustment first
What factors determine the speed of digestion?
Size of meal
Composition
Osmolarity
What hormone is involved in gastric phase of digestion?
Gastrin
What hormones are involved in the intestinal phase?
CCK and secretin
What is the order of the GI tract wall starting from the lumen (outside word)?
Mucosa > sub-mucosa > muscuylaris externa > serosa
When is neural signalling used?
When rapid and precise regulation is required
What are extrinsic reflexes?
Regulation and co-ordination of GI function over long distances e.g., complex behaviours such as swallowing.
Involves the CNS via the ENS.
What neural system is involved in extrinsic reflexes?
CNS - but always act via the ENS
What are intrinsic reflexes?
Regulation over centimeters (local reflexes) e.g., the relaxation of the internal anal sphincter in repsonse to rectal distention
Involves ENS only.
What neural system is involved in intrinsic reflexes?
ONLY the ENS
What is the function of the ENS?
Respond to internal stimuli (GI lumen contents)
What is the ENS response?
Occurs via two short reflex pathways:
(1) Myenteric Plexus - which controls motility.
(2) Submucosal plexus - which controls secretion and absorption.
Can the ENS function independantly of the CNS?
Yes
The ENS is a self contained system - it can perform short local reflexes (over cm’s) independant from the CNS.
What does myenteric plexus control?
muscularis layer = motlity
*located between inner circular msucle and outer longitudinal muscle layers.
What does the submucosal plexus control?
mucosa layer = secretion, absorption and movement of villi
What provides a route between CNS and ENS?
The autonomic NS neurons (PSNS and SNS) that include both motor (efferent) and sensoru (afferent) neurons.
*they are not part of the ENS themselves
What are the ENS neurons?
Afferent sensory (mechano/chemo sensory)
Interneurons
Efferent neurons (motor and secretory)
What are the stimulatory neurotransmitters of the GI tract?
Acetylcholine and tachykinins (substance P, neurokinin A)
*PSNS
What are the inhibitory neurotransmitters of the GI tract?
NO (+ VIP and ATP)
*SNS
What are the 2 functions of the CNS in the GI tract?
(1) Intergration of responses to external stimuli - senses and emotions via ANS.
(2) Response to internal stimulus - GI lumen contents via long reflex path (ENS to CNS and back to ENS again = gut to brain and back again).
Does the sympathetic or parasympathetic pathway inhibit GI activity?
Sympathetic pathway
What does the sympathetic pathway release and what does it bind to?
Noradremaline and binds to a adrenergic receptors
What pathway stimulates GI activity?
Parasympathetic
What does the parasympathetic pathway release and what is it detected by?
ACh detected by muscarinic cholinergic receptors
What do afferent fibres of sensory ENS neurons detect?
Information regarding the state of gut and relay it to the CNS
What do efferent fibers of the ENS signal a repsonse to?
Smooth muscle cells or epithelial cells
Does the CNS directly innervate the GI tract?
No - it acts through the ENS
*Some exceptions
What are the exceptions to the rule that there is no direct innervation of the GI tract from CNS?
The upper structures involved ni swallowing and the external anal sphincters –> reason being that they both have skeletal muscle rather than GI tract smooth muscle
What is the relavtive length of pre and post ganaglionic axons in the SNS and PSNS?
SNS short then long
PSNS long then short
What layers of the gut are ENS sensory neurons located?
All layers
What is the speed of hormone interaction?
Slow and sustained
What are GI hormones secreted by?
enteroendocrine cells that are throughout the intestinal tract
What are the mechanisms of GI hormones?
Endocrine
Paracrine
Neurocrine
What memebrane are the receptors of enteroendocrine cells on?
Apical - meaning they respond to luminal changes - they respond by releasing granules containing homrones from their basolateral pole via exocytosis.
What is the difference between endocrine, paracrine and neurocrine?
Endocrine = released into blood to tarvel to target cell
Paracrine = neighbouring cells receptor on membrane
Neurocrine = release of neurotransmitter
What is the function of the GI tract immune system?
Barrier function
Active immune response
Modulator of GI tract and systemic physiology
What does the GI tract immune system respond to?
Food antigens, pathogens, commensal/mutualistic bacteria
What does the GI tract release in its immune response?
Histamine, prostaglandins, leukotrines, cytokines
How often is gut epithelia replaced?
Every 5 days = cell shedding
What are the components of the barrier function of gut epithelia?
Aborpsitve cells
Secretory cells
Stem cells
Paneth cells
Where are secretory cells located?
In crypts or glands
What houses a range of GI tract immune cells?
Mesenteric lympth nodes and Peyers patches
What are the GI tract immune cells?
Intraepitehlial lymphocytes
B cells
T cells
Mast cells
macrophages
eosinophils
What is the difference between phasic and tonic contractions?
Phasic contractions occur in the esophagus, gastric antrum (stomach), small intestine and large intestine. Whereas tonic contractions occur in the lower esophageal sphincter, pyoric sphincter, ileocecal and internal anal sphincters.
Phasic contractions are rhythmic contractions with each individual contraction lasting several seconds and repeating waves of contractions continuing for minutes to hours. Whereas, tonic contractions are long-acting sustained contractions with individual contractions lasting minutes to hours.
What is fasting motility and when does it occur?
The clearing of undigested material and secretions regulating the intestinal microflora and stimulating epitehlial cell turnover. Occurs 4 hours after eating.
What is fed motility?
It is the storage, propulsion and movement at a controlled rate and mixing when there is food/chyme in the GI tract.
When does the migrating motor complex start?
4-5 hours post meal absorption - during fasting
How long does the migrating motor complex last for?
2 hours (to get from stomach to end of the large intestine)
What are the phases of the migrating motor complex?
(1) Intense
(2) Inactive
(3) Intermittent
What is the function of the migrating motor complex?
It is the process that occurs during fasting and referred to as “housekeeping”.
Its clears undigested materials and secretions, r egulates intestinal microflora and is involved in epithelial cell turnover.
What regulates the migrating motor complex (fasting)?
Motilin
Where is motilin released from?
Hormonally it is released by intestinal m-cells to directly modulate muscle
What is the neuronoal effect of motilin?
It stimuates both the enteric and autonomic NS (neurocrine effect).
What allows for fed motility storage?
Relaxation of smooth muscle that allows the volume of the luminal contents to increase without change in pressure
Where does fed motility storage occur?
Stomach and the colon
What are two examples of storage in the stomach?
(1) Receptive relaxation - swallowing trigers reduced muscle tone as food is moved down to esophagus - allows food to enter the stomach without a change in pressure preventing gastrix reflux.
(2) Accommodation - Progressive relaxation in reposne to a volume chnage/stretch.
What is fed motility movement?
Motility patterns that move or propel chyme/food through the GI tract.
Can combine with other motility to produce complex patterns e.g., retropulsion which has a mixing function
Where does fed motility movement occur?
Oesophagus, stomach, small intestine and large intestine.
What is peristelsis?
The wave-like movements that push the contents of the GI lumen forward.
Movement is the result of contraction in ciruclar muscle layer forcing bolus forward = like squeezing bottom of toothpaste
What is fed motility mixing?
Motility patterns that mix chyme with enzymes and other secretions and expose chyme to absorptive surfaces.
*in the stomach mixing also contributes to mechanical digestion but this is complete by the time chyme gets released to the small intestine.
What is an example of motility mixing?
Segmentation
What is segmentation?
Circular muscle contraction in alternating segments causing the chyme to be moved back and forth in the intestinal tube.
What are the two types of smooth muscle?
Multi-unit (e.g., vascualr smooth muscle)
Unitary (e.g., GI tract smooth muscle)
What is multi-unit smooth muscle?
Individual muscle cells contracting independantly
What is unitary smooth muscle?
Cells contracting together = act as a syncytium.
What is the arrangement of unitary smooth muscle that enables cells to contract together?
There is extensive intercellualr communication: gap junctions electrically connect cells and adherens junctions physically connect cells.
What regulates unitary smooth muscle?
Hormones and ENS neurons
Myenteric plexus between muscle layers
How big are unitary smooth muscle cells?
5-20 um in diameter and around 500 um in length
What filaments are contained in unitry smooth muscle?
Actin and myosin
How does the arrangement of GI smooth muscle differ to skeletal muscle?
GI muscle is irregualr arrangements whereas SKM is striated
What are the interstitial cells of the Cajal (ICC)?
The pacemakers of the gut - they generate slow waves - therefore determine the frequency of contractions.
What do ICC cause rhythmic changes in?
The activity of Na+/K+ ATPase and membrane K+ conductance
Where are ICC’s located?
Stomach and small intestine - In smooth muscle layer close to myenteric plexus
Colon - In the boundary between the muscle and submucosal layer.
What determines the frequency of contractions in the GI tract?
ICC
What is the relationship between slow waves and GI tract contractions?
the frequency of slow waves is a property of the ICC in each region - faster in the proximal regions (digestion in duodenum) and slower in the distal regions (absorption in colon).
Approx how many contractions per a minute is there in the duodenum during digestion?
12-20
How many contractions per minute in the colon during absorption?
6-8
What determines the size of contraction in GI tract?
Action Potentials (if the memmbrane potential does not reach threshold there is no contract and the longer the potential is above threshold the more APS and the biggeer the contraction).
How is GI smooth muscle contraction initiated?
Increases cytisolic Ca2+, Ca2+ binds to calmodulin, activation of myosin light chain (MLCK), MLCK uses ATP to phosphoryalte myosin, actin and myosin interact and cross bridge cycles produce tension.
How does Ca2+ levels contribute to phasic contractions?
The more Ca2+ the more calmodulin/MLCK activation therefore the more contraction
*calmodulin is the Ca2+ binding protein - when Ca2+ binds to it MLCK is actiavted. MLCK causes the phosphorylation of light chains of myosin - a motor protein that is crucial for enabling the interaction between myosin and actin to form cross bridges that drive muscle contraction.
What are the methods of upregualtion of phasic contractions?
(1) Depolarisation
(2) Increase in intracellular Ca2+
How does depolarisation of the cell membrane upregualtion contractions:
Depolarisation opens up the voltage gated Na+ and Ca2+ channels in sarcolemma resulting in influx of Ca2+ which actiavtes the ryanodine receptor resulting in release of Ca2+ from the SR (Ca2+ induced Ca2+ release).
Activates contraction and increases the magnitude of contractions by increase duration of AP.
Increased duration of AP = more Ca2+ = more cross bridges.
How does an increase in the intracellualr Ca2+ upregulate contraction (Pharmomechanical contraction)?
Hormones and neurotransmitters bind to a receptor to induce Ca2+ release - Gaq siganlling pathway is actiavted > phhospholipase C > IP3 induced release of Ca2+ from SR to increase magnitude of contractions.
What are the three signals that contribute to the down-regualtion of phasic contractions?
(1) Hyperpolarisation of smooth muscle cell membrane (or decrease Ca2+)
(2) Increased activity of myosin light chain phosphatase (removes phosphate from myosin so cannot no longer enables myosin + actin interaction).
(3) Inhibtion/blocking of excitatory neurotransmission
What is an example of the inhibition of excitatory ENS neurotransmissions?
Opioid drugs
What does an increase in activity of myosin light chain kinase (MLCK) cause?
Phosphorylation of mysosin which is crucial for regulating actin-myosin interactions = increases contraction
What do hormones and neurotransmitteres regulate?
The magnitude/strength of contraction only - little effect on frequency of contractions
What determines the frequency of contractions?
ICC (varies by region)
What will increasing the amount of myosin light chain phosphatase do?
De-phosphorylate myosin and reduce cross bridge cycling = blocking excitatory neurotransmission decreases contraction.
How does stress effect GI motility?
Referring to the brain gut connection as a result of the ENS = “second brain”.
When we are stressed this is detected by the CNS which sends a message to the ENS via the SNS = causing activation of the CNS and deactivation of the PSNS.
When SNS is activated blood flow in the body is redirected away from non-vital organs which includes the GI tract.
ENS has a adrenergic receptors which sends inhibitory signal to smooth muscles decreasing the trigger forperistalisis waves.
NO increases the amount of myosin light chain phosphatase de-phosphorylates myosin and reduces cross bridge cycling decreasing strength of any contraction.
How does relaxation influence GI motility?
When you relax, your body is in a “rest and digest” state controlled by the PSNS. This state helps increase GI motility, promoting smoother and more efficient digestion by the release of ACh which binds to smooth muscle in the GI tract.
In contrast when you’re stressed, the body releases hormones like adrenaline and cortisol, which activate the “fight or flight” response. This can slow down or disrupt GI motility (the movement of food through the digestive system) because energy is redirected away from digestion to other parts of the body.
How do opioid drugs influence GI motility?
Inhibiton of excitatory ENS neurotransmission = opioid binds to opioid receptors in the myenteric plexus. These are Gai receptors which inhibit neurotransmission by ENS neurons. Excitatory signals are blocked and don’t get to the GI smooth muscle.
What is the technical word for chewing?
Mastication
What is the function of chewing?
Mechanical digestion - it allows for swallowing
Mixes food with salvia - tasting and diluting food
Stimulus for cephalic phase of gastric digestion
Is chewing under voluntary or involuntary control?
Chewing is under volunatily control but with involunatry reflex components from the brainstem.
What is chewing initiated by?
The bolus in the mouth
What is the function of swallowing?
Swallowing is the rapid transfer of food from mouth to the stomach.
It converts mouth and pahrynx pathways from gas transfer to food transfer function.
Prevents reflux.
Explain the swallowing process:
Swallowing is the combination of oral and esophageal events:
It is initiated from food being forced into the pharynx by the tounge activated stretch receptors that send siganls to the brainstrem to intitate swallowing.
Soft palate pushes forward preventing food from entering the nasal passage (stops food going out nose).
The epiglottis moves down to cover the entrance of the trachea preventing the aspiration of food (stops food going into the lungs).
Upper esophageal sphincter relaxes and opens to allwo food to enter the esophagus.
The loweresophageal sphincter opens at the start of swallowing so that food can enter the stomach and closes after peristalsis wave.
Esophagus smooth muscle contracts ad a peristaltic wave pushes food to the stomach - this lasts about 9 sections.
How long does esophagus peristalsis last?
About 9 seconds
Does the upper or lower esophageal sphincter open first?
Upper
When does the lower esophageal sphincter close?
After peristalsis wave
What is receptive relaxation?
Receptive relaxation in the stomach is part of the swallowing process - it is when the smooth muscles of the proximal part of the stomach relaxes and dilates for food entering the stomach.
it is the reduction of gastric tone with swallowing controlled by CNS.
What are the controls of swallowing?
oral events are under volunatry control (we decide when we initiate swallowing).
But once we swallow stretch receptors are activated which activates an involuntary response (relfex).
What muscles are under involuntary control during swallowing?
Pharyngeal muscles
Esophageal msucle
Lower smooth muscle
What is the difference btween striated muscle and smooth muscle control?
Striated muscle is controlled directly by swallowing center whereas smooth muscle is controlled indirectly (e.g., the ENS modulated by swallowing centre).
What is the junction of smooth and striated muscle called?
The transition zone
What does food in the esophagus initiate?
Primary peristaltic wave
What happens if food is not cleared from the esophagus by the primary peristaltic wave?
A secondary peristaltic wave occurs - this is repeated until food is cleared.
What does relaxation of proximal stomach cause?
Reduction in stomach pressure below esophageal pressure to prevent gastric reflux
What does GERD stand for?
Gastroesophageal reflux disease
What is gastroesophageal reflux disease (GERD)?
Reflux of acid chyme into the esophagus causing irritation to esophageal mucosa - leading to symptoms such as heart burn, cough etc
What is a symptom of irriatetd esophageal mucosa?
Heart burn
What are the causes of GERD?
Abnormal relaxation of LES
Damage to the gastroesophageal barrier (causing coughing and vomiting)
Lack of receptive relaxation for gastric accomodation
Conditions that increase gastric pressure
Excessive gastric secretion
Infection with H. Pylori
What is treatment for GERD?
Antacids that neutralise gastric HCI
Antihistamines and protein pump inhibitors that stop HCI production
Diet and other lifestyle changes
Surgery to treat H. Pylori
What is the anti reflux role of the upper esophageal sphincter?
prevents air entering the esophagus
What is the anti reflux role of the lower esophageal sphincter?
3-5cm zone of high pressure that is higher than gastric pressure = prevent movement from stomach back into eso because wouldn’t move from low to high pressure.
What are the anti reflux roles of the stomach?
Storage functions to maintain low pressure as volume increases
Receptive relaxation - stomach relaxes when esophagus sends food down
Reduction of gastric tone with swallowing - tone decreases to allow stomach tp be more compliant and thus smoother accomodation.
Gastric Accomodation - stomach accomodation of shape and size to ampunt of food it recieves.
Reflex relaxation of proximal stomach with gastric detention
What are the three key sections of the stomach?
Proximal stomach
Mid body
Distal stomach
What is the primary function of the proximal stomach?
It is the site of storage
Where is the fundus of the stomach?
In the proximal stomach
What is the primary function of the mid body of the stomach?
It is the transitional area - chyme is moved from storage in the proximal stomach for active mechanical digestion
What are the components of the distal stomach?
Distal body, antrum and pylorus
What is the primary function of the distal stomach?
Mechanical digestion and controlled release
What are the types of gastric motility?
Storage
Propulsion (peristalsis)
Retropulsion
Controlled delviery to the duodenum
What is retropulsion?
Mixing function - combination of peristalic contraction (which pushes food forward) and pyloric sphincter contraction (that pushes food backwards)
What is the controlled released to the duodenum?
Changing contraction/relaxation of the pyloric sphincter - short periods of opening that allows the entry of food to match capacity (volume and secretion rate).
What does storage in the proximal stomach allow for?
Relaxing motilty allows the stomach to accommodate food without changes in pressure
What are the two types of proximal stomach storage?
Receptive Relaxation
Gastric Accomodation
What two things is peristalsis the basis of?
Retropulsion and the controlled release to the duodenum
Is the pyloric sphincter open or closed during retropulsion?
Closed (open for the controlled relase to the duodenum).
When does peristelsis begin?
5-10 minutes after the arrival of food
What occurs 0-60 minutes after eating?
Gentle ripples
What results in the backwards retrograde flow of content towards the fundus?
The pyloric sphincter contracting at the same time as peristaltic contractions occur.
Explain the sieve effect in the release to the duodenum:
The pyloric sphincter opens more or less during peristalsis depending on the rate of release. This is to match delievery of food to small intentine with its ability to handle food e.g., its enzyme and bicarbonate content.
Does the frequency of contractions change throughout the GI tract?
No
What is the frequency of contractions in the GI tract determined by?
Slow waves/pacemaker cells = ICC
What is the frequency of contractions in the GI tract?
3 per minute
What does force of contractions in the GI tract depend on?
Depends on the amount of time of each wave is above threshold
During peristalsis in the small intestine - is ascending or descending circualr muscle movement contraction?
Ascending circular muscle contraction
Descending circular muscle relaxation
How many times a day do high intensity peristelic contractions occur?
once or twice a day (propels contents into the rectum = defecation)
What stops spontaneous opening of the external anal sphincter?
Rectoanal inhibitory reflex (RAIR)
Is the opening of the external anal sphincter under voluntary or involuntary control?
Voluntary - conscious control of skeletal muscle - it relaxes when defecation is appropriate.
What is the most common feed motility pattern in the small intestine?
Segmentation
