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 tume. 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 mechanically.

EMPTYING: this is carefully regulated to ensure adequate acidification/neutralisation, action of enzymes, mechanical breakdown and to avoid swamping of the duodenum.

Gastroparesis 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

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

LIQUIDS:

• rapidly disperse, empty without lag time
• rate of emptying is influenced by the nutrient content (nutirnet-containing liquids retained longer)

SOLIDS:

• 2 phases (lag time and linear phase); duration of lag time is related to size of particle
• liquids part is emptied and solid component is retained in proximal stomach
• trituration of larger particles to smaller ones (trituration is a form of reducing particle size or creating a homogenous solution through thorough mixing)
• the pylorus regulates the passage of materal

FATTY FOODS:

• liquefy at body temperature; float on top of liquid layer and empty slowly
• fats are potent inhibitors of gastric motor events and gastric emptying

INDIGESTIBLE SOLIDS:

• not empties in immediate post-prandial period
• MMC acitivity (see later)

Question 5

List some determinants of the rate of gastric motility.

Answer 5

• type of food eaten: carbs > protein > fatty foods > indigestible solids
• osmotic pressure of duodenal contents: hyperosmolar 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 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.

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)
• glucagon

Motilin, on the other hand, increases fundic contractions.

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 decreases intestinal motility (colonic motility)

Question 9

Describe the feedback control of gastric emptying.

Answer 9

Contraction of the middle antrum elicits a descending inhibitor reflex, causing the relaxation of the pylorus (via NO/VIP).
Another part of the reflex is that duodenal stimuli (eg. presence of acidic chyme or oleic acid) induces the excitatory reflex, leading to contractions of the pylorus (increased tone). This prevents the duodeno-gastric reflux.

Note that the pyloric sphincter can contract on response to antral or duodenal rhythm (eg. fatty acids in the duodenum). The contraction of the pylorus may cause liquids in the antrum to be squirted into the duodenum.

Gastro-gastric reflexes provide a balance between the gastric reservoir and the antral pump. The distention of the reservoir stimulates antral contractions. The distension of the antrum enhances and prolongs relaxation of the reservoir.

Question 10

What are the different components of motility in the intestine?

Answer 10

• segmentation (mixing contractions): stationary contractions and relaxation
• peristalsis (propulsive): in the stomach (3 waves/min)
• migrating motor complex
• mass movements (evacuation)

Question 11

What are the phases of motor activity?

Answer 11

PHASE 1: quiscence/ quiet period
PHASE 2: irregular propulsive contractions
PHASE 3: burst of uninterrupted phasic contractions (peristaltic rush)

Question 12

Describe segementation and its role in the GI tract.

Answer 12

Segmentation originates in the pacemaker cells (ICC). Segmentation creates divisions and subdivisions of chyme, bringing chyme in contact with intestinal walls. The chyme is divided, subdivided and mixed with luminal contents and pushed back and forth. Segmentation causes the slow migration of chyme towards the ileum.

The duodenum/jejunum contract 10-12 times per minute, while the ileum contracts 8-9 times per minute.

Question 13

What is the difference between peristalsis and segmentation?

Answer 13

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 properl it towards the anus (some localisation).

Question 14

Describe the migrating motor complex (MMC).

Answer 14

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 is 90-120 minutes.

Question 15

What are the functions of the MMC?

Answer 15

• ‘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 removed dead epithelial cells by abrasion
• 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 16

Describe the control of the MMC.

Answer 16

Breifly, 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 17

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

Answer 17

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 enhanced or suppressed by extrinsic innervation (ie. parasympathetic/sympathetic). Sympathetic and parasympathetic activity inhibit and stimulate the motility, respectively.

Pain and fear decrease motility.

Question 18

Describe storage in the large intestine.

Answer 18

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.

It contains ‘fermentation chambers’ which allow for the hydrolysis of fibre and indigestible nutrients, leading to faeces formation.

Question 19

Describe the motility of the large intestine.

Answer 19

1. Segmental or haustral contractions mix the contents; this is a key role for taenia coli longitudinal muscle.
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 missing
• fermentation
• slow propagating - slow aboral flow

Question 20

How does the hypothalamus detect food in the gut?

Answer 20

The outer muscle layer of the gut is covered by the serosa, which is continuous with the mesentery containg blood vessels, lymph vessels and nerve fibres.
Sensory neurones are connected to the 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.

Along the length of the sympathetic trunks are ganglia known as the ganglia of the sympathetic trunk, sympathetic ganglia or paravertebral ganglia. The ganglia are distinguished as cervical, thoracic, lumbar, and sacral, except in the neck.

Question 21

Describe carbohydrate (CHO) digestion and absorption.

Answer 21

• they 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 22

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

Answer 22

Galactose is actively transported by the luminal glucose carrier system, and is a competitive inhibitor of glucose transport.

Fructose has no effect on the absorption of glucose and galactose. Fructose is not actively transported by the enterocytes, but is absorbed by a carrier-mediated, facilitated diffusion system, where energy is not required.
The sodium-potassium ATPase pump is located in the basolateral membrane.

Question 23

Describe the movement of fructose from the intestinal lumen to the blood and various tissues.

Answer 23

GLUT5 is specific for fructose, with no ability to transport glucose or galactose. It is also insensitive to phloretin and cytochalasin B (GLUT2 transports fructose, glucose and galactose; it is sensitive to phloretin and cytochalasin B; responsible for fructose uptake across the hepatic plasma membrane into the liver and the basolateral membrane of the intestinal and renal epithelial cells).

After apical transport mediated by GLUT5, fructose is transported across the basolateral membrane by GLUT2.

Question 24

Describe protein digestion and absorption.

Answer 24

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 25

Describe amino acid transport.

Answer 25

Amino acids are transported on a sodium-coupled carrier system similar to that for glucose. There are separate 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 26

Generally, describe the digestion of lipids.

Answer 26

Triglycerides(TGs) are the majority (90%) of dietary lipids. These also include phospholipids, cholesterol, fat-soluble vitamins (A,D,E,K).

Dietary TGs are broken down into simpler units to facilitate absorption.
In the mouth, salivary lipase digests a small fraction of the TGs. However, most dietary TGs are digested in the small intestine.

TGs must be dissolved in the aqueous phase before they can be digested.

Question 27

In detail, describe the digestion of lipids.

Answer 27

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.

Lipase action requires the emulsification of TGs by bile salts (which dissolve TGs in water). Pancreatic lipase binds to the surface of the small emulsion particles.

Question 28

Describe micelles.

Answer 28

Micelles are lipid molecules that arrange themselves in a spherical form in aqueous solutions. The formation of a micelle is a response to the amphipathic nature of fatty acids; that is that they contain both hydrophilic and hydrophobic regions (polar head group and long hydrophobic chain).

Simple lipid molecules (such as cholesterol, phospholipids, fatty acids, 2-monoglycerides or 2-MG, fat-soluble vitamins, and lyso-lecithin_ diffuse into the lipophilic core of the simple bile micells and form a mixed micelle. The mixed micelles carry the major part of all the lipids that are absorbed by the intestinal microvilli.

Question 29

Summarise the digestion and transport of lipids

Answer 29

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 MGs and FFAs.
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 MGs and fatty acids leave the micelle and passively diffuse through the lipid bilayer of the luminal membranes.
5. The MGs and FFAs 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, the central lacteals.

Question 30

Describe disorders of fat digestion/ absorption.

Answer 30

Disorders such as gallstones, pancreatitis, Crohn’s Disease, and liver disease can lead to fat malabsorption (steatorrhoea or fat-diarrhoea = excess fat in the faeces).