Transport Along and Across the Alimentary Tract

Question 1

How is the gastric reservoir emptied?

Answer 1

Its emptying is controlled by tonic contractions and peristaltic waves
Tonic contractions are under the influence of pacemaker cells, the interstitial cells of cajal and the depolarisation that occurs within those cells
We also have this backflow which allows the churning of digesta in the stomach
Tonic contractions can last from mins to hrs

Question 2

What is gastric emptying dependent upon?

Answer 2

It is dependent upon:
1. Propulsive force generated by the tonic contractions of proximal stomach (where the fundus is)
2. Stomach’s ability to differentiate types of meals ingested and their components
The effects of fatty, hypertonic, acidic chyme in the duodenum on gastric emptying:
They decrease the force and rate of gastric emptying

Question 3

How is each consistency emptied?

Answer 3

Gastric emptying of a liquid, semi-solid meal; normal curves
Liquids pass in spurts
Solids are broken down to 1-2mm sizes
Large indigestible materials remain; cleared by MMC or vomiting
The use of MMC is called the housekeeping process

Question 4

What are the determinants of the rate of gastric motility?

Answer 4

Type of food eaten: carbohydrates>protein>fatty foods> indigestible solids
Osmotic pressure of duodenal contents; hyperosmolar chyme (lots of solid food) ↓ gastric emptying
Vagal innervation upon over-distention ↓ gastric motility
Hormones (somatostatin, secretin, CCK, GIP): inhibit emptying
Injury to intestinal wall and bacterial infections ↓ motility

Question 5

How is gastric motility controlled myogenically?

Answer 5

Intrinsic basic electric rhythm (BER)
BER allows the smooth muscle cell to depolarise and contract rhythmically when exposed to hormonal signals
Stomach muscle cells produce electric depolarisations form resting potential
And move ripples towards the antrum
Fundus is under vagal excitatory control
Slow waves from ICC- regular recurring migrating ripples (3 waves/min) known as BER (a rhythm of depolarisation-repolarisation)

Question 6

How is gastric motility controlled through neurohormonal control?

Answer 6

The following mediate a decrease (generally) in fundic motor activity:
Cholecystokinin (CCK)
Secretin
VIP
Somatostatin
Duodenal distension, duodenal acid
Gastric-releasing peptide (GRP)
Motilin increase fundic contractions

Question 7

How is movement of chyme controlled in the small intestine?

Answer 7

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

Question 8

How is gastric emptying regulated through negative feedback?

Answer 8

Gastric emptying is regulated by negative feedback systems e.g.
Antral over-distension- vago-vagal reflex
Duodenal over-distention and chemical stimulation- vago-vagal reflex and hormones
Note that pyloric sphincter contracts in response to antral or duodenal rhythm; fatty acids in duodenum cause contraction of pylorus

Question 9

How is gastric motility regulated?

Answer 9

Regulation elicited from the small intestine and middle antrum
If there is acidic chyme in the duodenum it will initiate an ascending excitatory reflex
That will cause pyloric contraction stopping the acidic chyme from moving along
Note that the behaviour of the pylorus is context-driven

Question 10

What is the motility in the intestine like?

Answer 10

Segmentation (mixing contractions)- stationary contraction and relaxation
Peristalsis (propulsive)- in stomach (3waves/min)
Migrating motor complex
Mass movement (evacuation)
Phases of motor activity:
Phase 1- quiescence/quiet period- when you have just eaten
Phase 2- irregular propulsive contractions- allow movement of food to duodenum
Phase 3- burst of uninterrupted phasic contractions ( called the peristaltic rush)

Question 11

How does segmentation happen?

Answer 11

Originates in the pacemaker cells (ICC)
Segmentation -> divisions and subdivisions of chyme, bringing chyme in contact with intestinal walls
Segmentation causes the slow migration of chyme towards ileum
Duodenum/jejunum- 10-12 contraction/min,
Ileum- 8-9 contractions/min so as you move towards the ileum it slows down

Question 12

Why does the regulation of peristalsis require neural reflexes?

Answer 12

Distension of that distended area, area is innervated by neurons, causes the neurons to pick that distension up, as that happens there is a need to contract to move it along
As the bolus moves to next segment that segment needs to relax

Question 13

What role do circular muscles play in peristalsis?

Answer 13

The circular muscles contract behind the bolus of food but the longitudinal muscles relax
As they relax, that will allow the bolus of food to move along as it causes the area to be less ridged
The circular muscles next to the bolus relax as the circular muscles behind push it from the back

Question 14

What is the circuit for the small intestinal peristaltic reflex?

Answer 14

Luminal stimuli elicit vago-vagal reflexes which activate integrating and program circuits of the enteric nervous system
These activate specific motor-neurones responsible for specific contractile pattern

Question 15

What is the migrating motor complex (MMC)?

Answer 15

Highly organised motor activity
Cyclically recurring sequence of events
Occurs between meals when the stomach/intestine are ‘empty’
Starts in lower portion of stomach and tends to sweep the length of the stomach
Only phase III is of interest
Burst if high frequency, large amplitude contractions that migrate along the length of the intestine and die out
Interval between phase IIIs is 90-120min

Question 16

What is motor activity in the small intestine in the fed state?

Answer 16

Mixing contractions; segmentation, mixes and stirs contents with enzymes, prevents unstirred layer formation
Peristaltic contractions (slow waves): these move the contents in an oral to anal direction (law of the gut)
Local reflex mediated via ENS but can be enhanced or suppressed by extrinsic innervation (i.e. parasympathetic/sympathetic); ↑sympathetic and parasympathetic inhibit and stimulate motility, respectively
Pain and fear ↓ motility

Question 17

What is motility like in the large intestine?

Answer 17

Motility in the large intestine is complex and poorly understood
Storage particularly whilst water is absorbed from contents
Intensive mixing and slow movement of waste and indigestible material aborally
Contain ‘fermenting chambers’ which allow the hydrolysis of fibre and indigestible nutrients
-> faeces formation

Features of motility in the large intestine:
Intensive mixing
Fermentation
Slow propagating- slow aboral flow

Question 18

What are the stages of motility in the large intestine?

Answer 18

1. Segmental or haustra; contraction-mix contents/ key role for taenia coli longitudinal muscle
   
   2. Peristalsis; slow in large intestine in comparison to small intestine; moves contents towards the anus; distension initiates contraction
   3. Mass movement; powerful contraction of mid-transverse colon that sweeps colon contents into rectum (responsible for colonic evacuation)

Question 19

Why do diarrhoea and constipation happen?

Answer 19

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

Question 20

What is the gross and microscopic structure of the small intestine?

Answer 20

The small intestine; epithelial folds, villi and microvilli (large surface area- an internal surface area of 200m2)
All dietary nutrients, water and electrolytes that enter the upper small intestine are absorbed
Crypt cells are important for signalling and defence, they detect things that should not be there
They can also regenerate

Question 21

How are things transported across the enterocytes?

Answer 21

Transcellular is when you have transport through a cell (in this case enterocyte)
Tight junctions allow the transport of solutes
Paracellular is when you have transport from one cell to another

Question 22

How are carbohydrates digested and absorbed?

Answer 22

Can only be absorbed in the form of monosaccharides
Complex CHO reduced to disaccharides by amylases
Specific brush border enzymes convert disaccharides to monosaccharides (e.g. glucose and galactose
Digestion of carbohydrates occurs in two stages:
In the intestinal lumen where you have the salivary and pancreatic amylases (pancreatic amylases will be secreted with the pancreatic juices coming from the gallbladder)
So when starch is broken down into different components; sucrose, glucose oligomers, lactose brush border enzymes can then act on them
The sucrose can be acted on by brush border enzymes called sucrase (enzymes just around the brush border around the villi)
The sucrose can be converted to glucose and fructose
Lactose is broken down by lactase to give glucose and galactose
Glucose oligomers can be acted upon by glucoamylase to give you glucose

Question 23

How are glucose and galactose transported?

Answer 23

Glucose and galactose are rapidly absorbed by a secondary active transport process
So when you look towards the basolateral end, usually there is a lot of sodium coming out of the cell into blood making a gradient where sodium needs to come in
So when going back 2 sodium ions a glucose or galactose molecules goes with them
So this is done through this transporter called the SGLT1
Now the glucose is inside the blood the glucose goes through a transporter called Glut-2 from the basolateral end to the blood
Fructose can get into the cell passively through facilitated diffusion and then into the blood through a transporter called Glut-5
Glut5 and Glut2 function in series to promote fructose absorption

Question 24

How are proteins digested and absorbed?

Answer 24

Polypeptides produced by action of pepsin
Pepsin to start with is inactive as pepsinogen and activated through hyperacidity
Polypeptides, di- and tr-peptides by action of pancreatic proteases
Di-peptidases in brush border complete digestion to amino acids
Amino acids enter enterocytes quite easily
Once di and tripeptides are in the enterocytes there are cytoplasmic peptidases which break them down to amino acids so they can be transported across the basolateral side into the blood
Some dipeptides and tripeptides can escape this

Question 25

How are amino acids transported?

Answer 25

Amino acids (AAs) are transported on a sodium-coupled carrier system similar to that for glucose
The basolateral side is easily permeable to amino acids
Separate carriers for different types of Aa
Some di- and tri-peptides are transported on a carrier system using inwardly directed H+ gradient (so the same way that they enter the enterocytes)

Question 26

Where are lipids digested?

Answer 26

Triglycerides (TGs) form the majority (90%) of dietary lipids
Also include phospholipids, cholesterol, fat soluble vitamins (A, D, E, K)
Dietary TGs are broken into simpler units to facilitate absorption
Mouth- salivary lipase digests a small fraction of the TGs
Most dietary TGs are digested in the small intestine
But TGs are water-insoluble; chyme (has got an emulsion of large fat particles in water); lipase is water-soluble and these two things don’t work together so
TGs must be dissolved in the aqueous phase before they can be digested

Question 27

How are lipids digested?

Answer 27

Digestion and absorption of lipids are facilitated by two important processes:
-Emulsification, aided by the secretion of bile salts
-Micelle formation, accumulation of triglycerides and fatty acids into the micelle helping bring them closer tot eh epithelial surface of the brush border
Gastric lipase breaks down approx. 10-30% of fats (inefficient)
Remainder digested by pancreatic lipase
Triglycerides are 1 glycerol and 3 fatty acids
Lipase action requires the emulsification of TGs by bile salts, stored in the gal bladder (dissolves TGs in water) and so that the pancreatic lipase can get to the core of the particles
Pancreatic lipase binds to the surface of the small emulsion particles
Most bile is reabsorbed (around 95%)

Question 28

How are micelles further digested?

Answer 28

These micelle will make its way very close to the brush border
Once it gets close to the brush border, it kind of fuses through exocytosis/pinocytosis
These monoglycerides will reform into triglycerides then getting coated by an apolipoprotein forms chylomicrons which are extruded and go into the lymphatic system, into the lymph via the lacteals (it can’t go into blood directly)
Then from the lymphatic system it goes into the blood through thoracic duct located near the subclavian vein near the neck
The short free fatty acids go into a portal vein

Question 29

What are some disorders of fat digestion/absorption?

Answer 29

Disorders such as gallstones, pancreatitis, Crohn’s disease and liver disease can lead to fat malabsorption
When gallstone happen they can impact on the cystic duct blocking the secretions from the gallbladder specifically bile salts
Steatorrhea or fat-diarrhoea= excess fat in faeces