Transport along and across the GI tract Flashcards
What does gastric accommodation decrease?
Decreases cholinergic activity
What factors promote accommodation?
VIP/NO promote accommodation
Where does tonic contraction start from?
Starts from the top of the antrum
What does tonic contraction impact on?
Impact on the propulsive forces
What does tonic contraction lead to?
Lead to the emptying of gastric reservoirs
What does the proximal stomach do to store food at low pressure?
the proximal stomach relaxes to store food at low pressure whilst it is acted upon
by acid, enzymes and mechanically
Why is emptying carefully regulated?
o this is carefully regulated to ensure adequate acidification/neutralisation, action of enzymes, mechanical breakdown and to avoid swamping of the duodenum.
What is gatroparesis and what is the stomach unable to do?
gastroparesis is a chronic condition in which the stomach cannot empty itself of food in the normal way, causing food to pass through it slowly
Steps involved in the emptying of food contents
1) contraction around the antrum area
2) pyloric sphincter will be contracted
a. grinding action of the antrum will make the particles smaller
What happens to large food particles?
- Large food particles are retained in the proximal part of the stomach; antrum repulses them→ mixing and grinding with digestive juices
What is gastric emptying dependent on ?
- Propulsive force generated by the tonic contractions of proximal stomach
- Stomach’s ability to differentiate types of meals ingested and their components
What decrease the force and rate of gastric emptying?
fatty, hypertonic, acidic chyme in the duodenum
How does gastric emptying of a liquid occur?
- Liquids pass in spurts
How does Gastric emptying of solids occur?
- Solids are broken down to 1-2mm sizes
How does gastric emptying of large indigestive materials occur?
- Large indigestive materials remain
o Cleared by Migrating Motor Complex or vomiting
Emptying of liquids
- Rapidly disperse, empty without lag time
* Rate of emptying is influenced by nutrient content (nutrient-containing liquids retained longer)
In how many phases are solids emptyed and what are those phases?
• 2 phases (lag time and linear phase)
When solids are emptied, what happens to the liquid and solid component?
• Liquid part emptied and solid component is retained in proximal stomach
What regulates the passage of material?
• Pylorus regulates passage of material
What happens to fatty food at body temperature when they’re being emptied?
• Liquefy at body temperature; float on top of liquid layer and empty slowly
What are fats potent inhibitors of?
• Fats are potent inhibitors of gastric motor events and gastric emptying
How are indigestible solids emptied?
• Not emptied in immediate post-prandial period
What activity is involved with the emptying of indigestible solids?
MMC activity
What are determinants of the rate of gastric motility?
- Type of food eaten
- Osmotic pressure of duodenal contents
- Vagal innervation upon over-distension of the duodenum
- Hormones
- Injury to intestinal wall and bacterial infections
What does BER allow?
BER allows the smooth muscle cell to depolarise and contract rhythmically when exposed to hormonal signals
What do stomach muscle cells produce and what does it move?
Stomach muscle cells produce electric depolarisations from resting potential
And move ripples towards the antrum
What control is the fundus under?
Fundus is under vagal excitatory control
What can alter GI membrane potential and consequently what?
Stretch, ACh, parasympathetic stimulation and GI hormones can alter the GI resting membrane potential (-50mv to -60mV; average = -56mV) and consequently BER of GI smooth muscle.
What do slow waves not allow?
Slow waves alone do not allow action potential generation and contraction to occur
What determines the frequency of contraction in the GI?
The basal or basic electrical rhythm (BER) or electrical control activity (ECA) determines the frequency of the contractions in the gastrointestinal tract
When can the contraction of smooth muscle occur in gastric motility?
Contraction of the smooth muscle can occur when the BER reaches its plateau.
What does BER allow smooth muscles to do?
The basal electrical rhythm allows the smooth muscle cell to depolarise and contract rhythmically when exposed to hormonal signals.
What are ICC and where are they located?
The intestinal cells of cajal (ICC) are specialised pacemaker cells located in the wall of the stomach, small intestine, and large intestine.
What do the cell membranes of the ICC undergo?
The cell membranes of the pacemaker cells undergo a rhythmic depolarisation and repolarisation
What does the rhythm of depolarization-repolarisation of the cell membranes of the ICC create?
This rhythm of depolarization-repolarisation of the cell membrane creates a slow wave known as a BER, and it is transmitted to the smooth muscle cells.
What are factors which decrease BER?
Sympathetic system → NA
What are the effects of NA or adrenaline on membrane of GI smooth muscle?
Depolarisation of GI smooth muscle is caused by calcium-sodium entry
Repolarisation of GI smooth muscles is caused by K+ efflux
What mediate a decrease in fundic motor activity?
Cholecystokinin (CCK) Secretin VIP Somatostatin Duodenal distension, duodenal acid
What does motilin increase?
Increases fundic acitvity
What factors initiate and maintain peristalsis and mixing in the movement through small intestines?
Hormonal and nervous factors initiate and maintain peristalsis and mixing
What happens to the duodenum during movement through small intestine?
Localised distention of the duodenum
What increases intestinal motility?
Serotonin, insulin, Cholecystokinin (CCK), gastrin and motilin increase intestinal motility
What decreases intestinal motility?
Secretin decreases the activity
What does glucagon do to fundic motor activity?
decreases fundic motor activity
What system is gastric emptying regulated by?
regulated by negative feedback systems
Examples of negative feedback systems which control gastric emptying
Antral over-distension:
Vago-vagal reflex
Duodenal over-distension and chemical stimulation:
Vago-vagal reflex and
hormonesWhat can the pyloric sphincter contract in response to?
pyloric sphincter can contract in response to antral or duodenal rhythm (e.g. fatty acids in duodenum)
Where is regulation elicited from in gastric motility and emptying?
Regulation is elicited from the small intestine
Steps involved in motility in the intestine during gastric emptying
Segmentation (mixing contractions): stationary contraction & relaxation
Peristalsis (propulsive): in stomach (3 waves/min)
Migrating Motor Complex
Mass movements (evacuation)
What are the phases of motor activity on the motility of intestines?
Phase I: quiescence (state of inactivity)/quiet period
Phase II: irregular propulsive contractions
Phase III: burst of uninterrupted phasic contractions (peristaltic rush)
Where does segmentation originate?
Originates in the pacemaker cells(ICC)
What does segmentation lead to and what does it move?
Segmentation → divisions and subdivisions of chyme, bringing chyme in contact with intestinal walls
Moves chyme close to the surface of the intestinal mucosal cells
What does segmentation cause the slow migration of and towards what?
Segmentation causes the slow migration of chyme towards ileum
What is the difference between peristaltic contractions and segmenting contractions?
Peristaltic (propulsive) contractions spread the food out allowing digestive enzymes to mix with it, but primarily push the food towards the anus (global movement)
Segmenting (mixing) contractions primarily churn the food, but also propel it towards the anus - some localisation
What sort of activity is the migrating motor complex?
Highly organised motor activity
Where does migrating motor complex start from?
Starts in lower portions of the stomach
What is the functions of the MMC?
Removes dead epithelial cells by abrasion
Prevents bacterial overgrowth
Prevents colonic bacteria from entering small intestine
When does activity of the MMC occur?
Occurs following digestion and absorption of a meal
How are the contraction involved in MMC coordinated?
Contractions are coordinated by the enteric nervous system by pacemaker cells (interstitial cells of Cajal)
What is the activity of the MMC initiated by?
Initiated by the vagus nerve in upper tract
What does feeding inhibit the release of?
Feeding inhibits release of motilin
What decreases motility?
Pain and fear
What is the large intestine used for whilst what is happening?
- It is used for storage, particularly whilst water is absorbed from the contents
What chambers does the large intestine contain and this allows what and leads to the formation of what?
- Contains “fermenting chambers” which allow the hydrolysis of fibre and indigestible nutrients
o → Faeces formation
Steps involved in the motility of the large intestine
- Segmental or haustral contractions-mix contents/ key role for taenia coli longitudinal muscle (Haustra = sacculations of colon between taenia)
- Peristalsis: slow in large intestine in comparison to small intestine; moves contents towards the anus; distension initiates contraction
- Mass movement: powerful contraction of mid-transverse colon that sweeps colon contents into rectum (responsible for colonic evacuation).
- Large amplitude, long duration, slow propagating velocity is associated with motility in the large intestine
What are some features of motility in the large intestine?
- Intensive mixing;
- Fermentation;
- Slow propagating-Slow aboral flow
The disorders of motility, fluid secretion and absorption are important in the pathogenesis of what?
Disorders of motility, fluid secretion and absorption are important in the pathogenesis of diarrhoea and constipation
What is diarrhoea?
Diarrhoea = frequent (> 3x/day) discharge of liquid faeces
What is constipation?
o Difficulty/some constraint in the opening/emptying of the bowels (hard faeces)
What system does the guthave?
The gut has an intrinsic, enteric nervous system
What does the 1. Submucosal Meissner plexus regulate?
regulates the digestive glands
What is the Myenteric Auerbach plexus connected with?
- Myenteric Auerbach plexus: primarily connected with gut motility
What do nerve plexi contain and for what purpose?
- The nerve plexi contain local sensory and motor neurons as well as interneurons for communication
What receptors do motor neurons in the myenteric plexus contain and what substance is released?
Motor neurons in the myenteric plexus: ACh (M receptors) and Substance P release
What do inhibitory motor neurons release and what does this lead to?
Inhibitory motor neurons release VIP and NO= relaxation
What is the outer muscle layer of the gut covered by and what is this continuous with?
- The outer muscle layer of the gut is covered by the serosa, which is continuous with the mesentery containing blood vessels, lymph vessels and nerve fibres.
What are sensory neurons connected to and what do they detect and what do they respond to?
- Sensory neurons are connected to mucosal chemoreceptors, which detect different chemical substances in the gut lumen, and to stretch receptors, which respond to the tension in the gut wall, caused by the food and chyme.
What is there along the length of the sympathetic trunks and what are they distinguished as?
- Along the length of the sympathetic trunks are ganglia known as ganglia of sympathetic trunk, sympathetic ganglia or paravertebral ganglia. The ganglia are distinguished as cervical, thoracic, lumbar, and sacral and, except in the neck
How are crypts formed in the small intestine?
- The epithelia of the villi extend down into the lamina propria where they form crypts.
What resides in crypts and what are they involved in?
Many important cells reside in the crypts, including those involved in host defence and signalling.
Crypts cells contain stem cells, which replenish what?
The crypt cells also contain stem cells that replenish the epithelial cells further up the villi
Where does the lamina propria layer lie?
- The lamina propria layer lies beneath the epithelium
Function of villus cells
Absorption
Function of Crypt cells
Secretion
What is trans-cellular transport?
It is transport of solutes by a cell through a cell
What is paracellular transport?
It is the passage of solutes between cells
How can carbohydrates only be absorbed?
- Can only be absorbed in the form of monosaccharides
What are complex carbohydrates reduced to and by what for digestion and absorption?
- Complex CHO reduced to disaccharides by amylases
What enzymes convert disaccharides to monosaccharides?
- Specific brush border enzymes convert disaccharides to monosaccharides
In how many phases does digestion occur?
Occurs in 2 phases
What happens in the luminal phase?
- Luminal phase
o Amylase = hydrolyses starch into maltose
What are glucose oligomers?
o Molecular complex that consist of a few monomer units
How are glucose and galactose absorbed?
- Glucose and galactose are rapidly absorbed by a secondary active transport process
How else is galactose actively transported?
- Galactose is also actively transported by the luminal glucose carrier system
What is the luminal glucose carrier system a competitive inhibitor of?
competitive inhibitor of glucose transport
What does phlorizin block and when?
Phlorizin (phloritin/phloridzin) blocks the glucose absorption, when its glucose moiety binds to the transporter instead of glucose
Process by which glucose is transported
- Cytoplasmic Na+ is actively pumped out through the basolateral membrane by the Na+-K+-pump. The low intracellular [Na+] creates the Na+ gradient and energises the transport of hexoses over the luminal enterocyte membrane. Glucose symporter SGLT1, co-transports one glucose molecule into the cell for every two sodium ions it imports into the cell
Effect of fructose on absorption of glucose and galactose
- Fructose has no effect on the absorption of glucose and galactose
What is GLUT-5 specific for?
- GLUT5 is specific for fructose with no ability to transport glucose or galactose
What is GLUT-5 insensitive to?
insensitive to phloretin and cytochalasin B.
What is GLUT-2 responsibe for?
- GLUT2 is responsible for fructose uptake across the hepatic plasma membrane into the liver and in the basolateral membrane of the intestinal and renal epithelial cells
What happens to fructose after apical transfer and whats it mediated by?
After apical transport mediated by GLUT5, fructose is transported across the basolateral membrane by GLUT2.
By the action of what are polypeptides produced from?
Polypeptides produced by action of pepsin
What completes digestion of polypeptides to amino acids and where?
Di-peptidases in brush border complete digestion to amino acids
What do Cytoplasmic peptidases from the enterocytes and brush border peptidases cleave?
- Cytoplasmic peptidases from the enterocytes and brush border peptidases cleave the small peptides into single amino acids
What are cytoplasmic peptidases particularly active against?
cytoplasmic peptidases are abundant and particularly active against di- and tri-peptides.
How are amino acids transported?
- Amino-acids (AAs) are transported on a sodium-coupled carrier system similar to that for glucose.
How are some di, tri peptides transported?
- Some di- and tri- peptides are transported on a carrier system using inwardly directed H+ gradient
How are basic amino acids and phenylalanine absorbed?
- Basic amino acids and phenylalanine are absorbed primarily through facilitated diffusion from the gut lumen to the blood.
Where are most dietary TGs digested?
- Most dietary TGs are digested in the small intestine
What must happen to TGs before they’re digested?
o TGs must be dissolved in the aqueous phase before they can be digested
How is the digestion and absorption of lipids facilitated?
- Emulsification
2. Micelle formation
What else digests lipids?
digested by pancreatic lipase
What does lipase action require
- Lipase action requires the emulsification of TGs by bile salts
What does pancreatic lipase bind to?
Pancreatic lipase binds to the surface of the small emulsion particles
What are micelles?
- Micelles are lipid molecules that arrange themselves in a spherical form in aqueous solutions
What is the formation of micelles in response to?
The formation of a micelle is a response to the amphipathic nature of fatty acids
What do emulsion droplets lead to the formation of and what does digestion occur on?
- Emulsion droplets → micelles (200x smaller than emulsion droplets); digestion occurs on the micelles
Property of colipase
Amphiphatic
When micelles are small enough, where do they travel to?
The micelles are now small enough to be taken up by the enterocyte and into the lacteals and into the lymphatic system before travelling to the blood via the thoracic duct
What are the largest lipoproteins?
- Chylomicron
How do chylomicrons enter the lymphatic system?
- Chylomicrons enter the lymphatic system via lacteals, and then travel via lymph vessels and enter the blood via thoracic duct located near the neck – connect with left subclavian vein
What are Triacylglycerols of Chylomicrons & VLDL hydrolysed by and how are they released?
- So the chylomicrons are extruded from the absorptive cell by fusion of Golgi vacuole membranes with the plasma membrane, a process of reverse pinocytosis.
What can the chylomicrons not cross and so how do they enter the lymphatic syestem?
so they enter the lymphatics, via lacteals
What does absorption of a large number of chylomicrons cause?
Absorption of large numbers of chylomicrons causes the lymph draining from the small intestine to appear milky
What can lead to fat malabsorption?
- Disorders such as gallstones, pancreatitis, Crohn’s disease, and liver disease can lead to fat malabsorption
