Transport along and across the GI Tract

Question 1

What is the emptying of the gastric reservoir caused by?

Answer 1

• The transport of digesta from the gastric reservour into the antral pump is caused by two mechanims:
  
  • tonic contraction and peristaltic waves in the region of the gastric corpus.
• Tonic contractions are contractions that are maintained from minutes to up to hours at a time. They can occur in the stomach and the sphincters of the GIT.

Question 2

Describe storage and gastric emptying (and a disorder relating to it).

Answer 2

• STORAGE:
  
  • The proximal stomach relaxes to store food at a low pressure whilst it is acted upon by acid, enzymes and mechnically.
• EMPTYING:
  
  • This is carefully regulated to ensure adequate acidification/neutralisation, action of enzymes, mechanical breakdown and to avoid swamping of the duodenum (If the acidic conditions in the duodenum are not neutralised it could lead to the formation of a duodenal ulcer).
• Disorder: Gastroparesis:
  
  • ​It is a chronic (long-term) condition in which the stomach cannot empty itself of food in the normal way, causing food to pass through it slowly.

Question 3

What is gastric emptying dependent upon?

Answer 3

Gastric emptying is dependent upon:

1. The propulsive force generated by the tonic contractions of the proximal stomach.
2. The stomach’s ability to differentiate types of meals ingested and their components (weather it has carbohydrates, proteins, lipids in it).
   
   • Fatty, hypertonic, acidic chyme in the duodenum decreases the force and rate of gastric emptying.

Question 4

Summarise the emptying of different food components (liquids, solids, fatty foods and indigestable solids).

Answer 4

1. LIQUIDS:
   
   • Rapidly disperse, empty without lag time (There is no lag time because the size is small).
   • Rate of emptying is influenced by the nutrient content (nutrient-containing liquids retained longer).
2. SOLIDS:
   
   • 2 phases (lag time and linear/emptying phase).
   • Duration of lag time is related to size of particle.
   • Liquids part is emptied and solid component is retained in proximal stomach.
   • If the solid is large it has to be broken down (triturated) to 1-2mm in size in order to pass into the duodenum.
   • The pylorus regulates the passage of materal.
3. FATTY FOODS:
   
   • Liquefy at body temperature and float on top of liquid layer and empty slowly.
   • Fats are potent inhibitors of gastric motor events and gastric emptying.
4. INDIGESTIBLE SOLIDS:
   
   • They do not empty during the immediate post-prandial period (the period that comprises and follows a meal)
   • They are cleared by vomiting or MMC (migrating motor complex) that allows the cleansing of the stomach.

Question 5

List some determinants of the rate of gastruic motility.

Answer 5

• Type of food eaten:
  
  • carbs > proteins > fatty foods > indigestible solids.
• Osmotic pressure of duodenal contents:
  
  • hyperosmolar (increase in the osmolar concentration of body fluids) chyme decreases emptying.
• Vagal innervation upon over-distension decreases gastric motility.
• Hormones (somatostatin, secretin, CCK, GIP): inhibit emptying.
• Injury to intestinal wall and bacterial infections decreases motility.

Question 6

Describe the myogenic control of gastric motility.

Answer 6

• The Intestinal Cells of Cajal (ICC) are specialised pacemaker cells located in the wall of the stomach, small intestine and large intestine.
• The cell membranes of the pacemaker cells undergo a rhythmic depolarisation and repolarisation.
• This rhythm of depolarisation-repolarisation of the cell membrane creates a slow wave known as a BER, and it is transmitted to the smooth muscle cells.
• The intrinsic basal or basic electrical rhythm (BER) or electrical control activity (ECA) determines the frequency of the contractions in the GI tract.
• Contraction of the smooth muscle can occur when the BER reaches its plateau.
• The basal electrical rhythm allows the smooth muscle cell to depolarise and contract rhythmically when exposed to hormonal signals.
• Depolarisation of the GI smooth muscle is caused by calcium-sodium entry.
• Repolarisation of the GI smooth muscle is caused by K+ efflux (flowing out).

Question 7

List some factors that will mediate a decrease in fundic motor activity.

Answer 7

• Cholecystokinin (CCK).
• Secretin.
• VIP.
• Somatostatin.
• Duodenal distention, duodenal acid.
• Gastrin-releasing peptide (GRP).
• Motilin, on the other hand, increases fundic contractions.
• Glucagon also decreases fundic motor activity.

Question 8

How is movement through the small intestine controlled?

Answer 8

• Hormonal and nervous factors initiate and maintain peristalsis and mixing.
• Localised distention of the duodenum.
• Cholecystokinin (CCK), gastrin and motilin increase intestinal motility (colonic motility).
• Secretin (and insulin) decreases intestinal motility (colonic motility).

Question 9

Describe the feedback control of gastric emptying.

Answer 9

• Gastric emptying is regulated by negative feedback systems.
• When you have distension of the fundus that initiates exitatory effects within the antrum, leading to the contraction of the antrum. This contraction will tend to send inhibitory signals (inhibitory signals tend to be prolonged). Examples:-
  
  • Antral over-distension: Vago-vagal reflex.
  • Duodenal over-distension and chemical stimulation: Vago-vagal reflex and hormones (such as CCK).
• Note : the pyloric sphincter contracts in response to antral or duodenal rhythm; fatty acids in duodenum cause contraction of pylorus.

Question 10

Describe the regulation of gastric motility and emptying.

Answer 10

• When the duodenum has no food inside it, then the factors that promote the relaxation of the pyloric sphincter (NO and VIP) are released which allow the pylorus to relax and the middle antrum to contract. This is called the descending inhibitory reflex.
• If acidic chyme has just been squirted into the duodenum, it will be sensed by the enteric nervous system and it will not allow more acidic chyme to be squirted in. It will cause the pylorus to contract and increases the tone. This is called the ascending excitatory reflex. This prevents the forming of duodenal ulcer.

Question 11

What are the different components of motility in the intestine?

Answer 11

• Segmentation (mixing contractions): stationary contractions and relaxation (allows greater mixing of chyme with the secretions of the intestines).
• Peristalsis (propulsive): in the stomach [3 waves/min] (allows the mixing, continued digestion and absorption if nutrients of chyme in the intestines).
• Migrating motor complex: They are waves of electrical activity that sweep through the intestines in a regular cycle during fasting to cleanse the remaining food out of the intestines.
• Mass movements (evacuation): Getting rid of undigested material.

Question 12

What are the phases of motor activity?

Answer 12

• PHASE 1: quiscence / quiet period.
• PHASE 2: irregular propulsive contractions.
• PHASE 3: burst of uninterrupted phasic contractions (peristaltic rush) (its the rumbling sounds your stomach makes).

Question 13

Describe segementation and its role in the GI tract.

Answer 13

• Segmentation originates in the pacemaker cells (ICC) and tends to be more of a churning action.
• Segmentation creates divisions and subdivisions of chyme, bringing chyme in contact with intestinal walls.
• Segmentation causes the slow migration of chyme towards the ileum.
• The duodenum/jejunum contract 10-12 times per minute, whereas the ileum contracts 8-9 times per minute.

Question 14

Describe peristalsis and its role in the GI tract.

Answer 14

• On the outer surface of the GI tract there are longitudinal muscles which contract infront of the bolus of food. This shortens the area of the GI tract immediately infront of the bolus of food.
• On the inner surface of the GI tract there are circular muscles which contract behind the bolus of food. This pushes the food along the GI tract.

Question 15

Explain the circuit for the small intestinal peristaltic reflex.

Answer 15

• Whatever is in the intestinal lumen (food particles) such as glucose, long chain fatty acids, amino acids these can initiate activity within the gut.
• If there is fat present (lipids) CCK will be released.
• This will set in motion reflexs which will allow (in the case of CCK the gall bladder to contract and release bile.
• It doesnt have to rely on the higher centres of the brain as some of these processes can occur within the enteric nervous system in the gut lumen.
• This leads to the activation of specific motor neurones that are responsible for specific contractile pattern.

Question 16

What is the difference between peristalsis and segmentation?

Answer 16

• Peristaltic (propulsive) contractions spread the food out, allowing digestive enzymes to mix with it, but primarily push the good towards the anus (global movement).
• Segmenting (mixing) contractions primarily churn the food, but also propel it towards the anus (some localisation).

Question 17

Describe the migrating motor complex (MMC).

Answer 17

• It is highly organised motor activity, a cyclically recurring sequence of events.
• It occurs between meals, when the stomach / intestines are ‘empty’.
• It starts in the lower portion of the stomach.
• Only Phase 3 is of interest.
• There is a burst of high frequency, large amplitude contractions that migrate along the length of the intestine and die out.
• The interval between Phase 3s waves is 90 - 120 minutes.

Question 18

What are the functions of the MMC?

Answer 18

• It is the ‘intestinal housekeeper’.
• Indigestible residues are moved out of the stomach by large contractions and there is the wide opening of the pyloric sphincter during Phase 3.
• It removes dead epithelial cells by abrasion (scraping away).
• It prevents bacterial overgrowth.
• It prevents colonic bacteria from entering the small intestine.
• It occurs following digestion and absorption of a meal (empty stomach).

Question 19

Describe the control of the MMC.

Answer 19

• The control of MMC is not fully known.
• We know that the smooth muscle cells of the stomach can produce ‘slow waves’.
• These contractions are coordinated by the enteric nervous system by pacemaker cells (ICC).
• This is initiated by the vagus nerve in the upper tract.
• There is some evidence for cyclical secretion of the hormones motilin from the stomach and duodenum.
• Feeding inhibits the release of motilin.

ICC is for a complex network of specialised smooth muscle fibres; they lie between smooth muscle layers and can form synaptic connections with GI smooth muscle fibres.

Question 20

Describe the motor activity in the small intestine in the fed state.

Answer 20

• There are mixing contractions, such as segmentation, which mixes and stirs the contents with enzymes, and prevents an unstirred layer formation.
• There are peristaltic contractions (slow waves); these mover the contents in an oral to anal directions (law of the gut).
• It is a local reflex mediated via the ENS, but can be enhacned or suppressed by extrinsic innervation (ie. parasympathetic/sympathetic).
• Sympathetic and parasympathetic activity inhibit and stimulate the smotility, respectively.
• Pain and fear decrease motility.

Question 21

Describe storage in the large intestine.

Answer 21

• Storage occurs in the large intestine, particularly whilst water is absorbed from the contents.
• Intensive mixing and slow movements of waste and indigestible material occur aborally (away from the mouth).
• It contains ‘fermentation chambers’ which allow for the hydrolysis of fibre and indigestible nutrients, leading to faeces formation.

Question 22

Describe the motility of the large intestine.

Answer 22

1. Segmental or haustral contractions: mix the contents; this is a key role for taenia coli longitudinal muscle (these are a muslce structure that run along the middle of the large colon. Its presence allows the large intestine to have folds or sacculations. Within the sacculations you can have fragmentations occuring there).
2. Peristalsis: slow in the large intestine in comparison to the small intestine, moves the contents towards the anus; the distention initiates contraction.
3. Mass movement: powerful contraction of the mid-transverse colon that sweeps the colon contents into the rectum (responsible for colonic evacuation).

• Features of motility in the large intestine: -
  
  • Intensive mixing.
  • Fermentation.
  • Slow propagating - slow aboral flow (away from the mouth).
• The inflammation of the appendices epiploicae (fat filled peritoneum) can cause a lot of pain and can be mistaken for appendicitis.

Question 23

Describe diarrhoea and constipation.

Answer 23

Disorders of motility, fluid secretion and absorption are important in the pathogenesis of diarrhoea and constipation.

• Diarrhoea is the frequent (> 3 times / day) discharge of liquid faeces.
• Constipation is the difficulty / some constraint in emptying bowels (hard faeces).

Question 24

Describe the gross and microscopic structure of the small intestine.

Answer 24

• The small intestine is thin, has a large surface area (an internal surface area of 200 m²) and highly vascularised.
• The surface area is increased by the presence of epithelial folds, villi and microvilli.
• The small intestine can also replace itself (it has stem cells within the crypt cells that allow rejuvenation and replacement of dead cells).
• All dietary nutrients, water and electrolytes that enter the upper small intestine are absorbed.

Question 25

What are the two types of solute transport across the enterocyte.

Answer 25

1. Transcellular transport :-
   
   • Transport of solutes by a cell through a cell. E.g., transport of glucose from the intestinal lumen to extracellular fluid by epithelial cells.
2. Paracellular transport :-
   
   • Passage of solutes between cells.

Question 26

Describe carbohydrate (CHO) digestion and absorption.

Answer 26

• Carbohyrates can only be absorbed in the form of monosaccharides.
• Complex CHO is reduced disaccharides by amylase.
• Specific brush border enzymes convert disaccharides to monosaccharides (eg. glucose and galactose).

Question 27

Describe the transport of glucose and galactose across the apical membrane.

Answer 27

• The basolateral side (blood side) of the enterocyte (gut cell) tends to be transporting Na+ into the blood from the lumen.
• This creates a Na+ gradient.
• This driving force of Na+ allows glucose to come in with it.
• This cotransporter is called the Na+/glucose cotransporter (SGLT1).
• This same transporter is also good at transporting galactose.
• If galactose is able to get to the blood first it will inhibit glucose.
• Once glucose is within the cell there are glucose transporters called Glut-2 that will transport it to the blood.
• Fructose does not need any transporter, it is passively transported and moves from the cell to the blood via the Glut-5 transporter.

Question 28

Describe protein digestion and absorption.

Answer 28

• Polypeptides are produced by the action of pepsin.
• Polypeptides, di- and tri- peptides are produced by the action of the pancreatic proteases.
• Di-peptidases in the brush border complete their digestion to amino acids.
• Hydrolytic digestive products such as tripeptides, dipeptides and amino acids can be absorbed intact across the intestinal mucosa and into the blood.

Question 29

Describe amino acid transport.

Answer 29

• Amino acids are transported on a sodium-coupled carrier system similar to that for glucose.
• There are seperate carriers for different types of amino acids.
• Some di- and tri-peptdies are transported on a carrier system using an inwardly directed H+ gradient.

Question 30

Generally, describe the digestion of lipids.

Answer 30

• Triglycerides(TGs) are the majority (90%) of dietary lipids.
• These also include phospholipids, cholesterol, fat-soluble vitamins (A,D,E,K).
• Dietary triglycerides are broken down into simpler units to facilitate absorption.
• In the mouth, salivary lipase digests a small fraction of the triglycerides.
• However, most dietary triglycerides are digested in the small intestine.
• But TGs are water-insoluble; chyme (emulsion of large fat particles in water); lipase is water-soluble.
• So, triglycerides must be dissolved in the aqueous phase before they can be digested.

Question 31

In detail, describe the digestion of lipids.

Answer 31

• The digestion and absorption of lipids are facilitated by two important processes:
  
  1. Emulsification.
  2. Micelle formation.
• Gastric lipase breaks down approximately 10-30% of fats, the remainder is digested by pancreatic lipase.
• When the duodenum detects the presence of lipids in the squirted liquid the gall bladder will contract under the influence of CCK to release bile into the duodenum.
• This is done because the lipid needs to be emulsified and allow micelle formation to occur.
• These processes make the lipid molecules much smaller and increase their surface area.
• This allows the enzymes secreted from the pancreas (pancreatic lipase) to get to the core of the lipid.
• Pancreatic lipase binds to the surface of the small emulsion particles and breaks down triglycerides to fatty acids and glycerol.

Question 32

Summarise the digestion and transport of lipids

Answer 32

1. Dietary fat in the form of large fat globules composed of TGs is emulsified by the detergent action of bile salts into a suspension of smaller fat droplets. This lipid emulsion prevents the fat droplets from coalescing and thereby increases the surface area available for the attack fo pancreatic lipase.
2. Lipase hydrolyses TGs into monoglycerides and free fatty acids.
3. These water-insoluble products are carried in the interior of water-soluble micelles, which are formed by bile salts and other bile constituents, to the luminal surface of the small intestine epithelial cells.
4. When a micelle approaches the absorptive epithelial surface, the monoglycerides and fatty acids leave the micelle and passively diffuse through the lipid bilayer of the luminal membranes.
5. The monoglyceride and free fatty acids are resynthesised into TGs in the epithelial cells.
6. These TGs aggregate and are coated with a layer of lipoprotein to form water-soluble chylomicrons, which are extruded through the basal membrane of the cells by exocytosis.
7. Chylomicrons are unable to cross the basement membrane of blood capillaries, so instead they enter the lympathic vessels via the central lacteals.

Question 33

Describe disorders of fat digestion/ absorption.

Answer 33

Disorders such as gallstones (they affect the release of bile into the duodenum which affects the digestion of fats), pancreatitis, Crohn’s Disease (inflammations of the gut), and liver disease (prodlem in the synthesis of bile) can lead to fat malabsorption (steatorrhoea or fat-diarrhoea = excess fat in the faeces).