GI VII

Question 1

What is the most significant site for digestion and absorption of nutrients in the GI system?

Describe.

Answer 1

small intestine

Intense motility and secretions in the lumen and a large surface area of mucosal cells are the basis for digestion/absorption of nutrients.

Increased gallbladder contraction.

Relaxation of the sphincter of Oddi.

Secretion of pancreatic and biliary juices.

Regulation of gastric emptying (control of pylorus).

Inhibition of gastric secretion.

Question 2

Describe gastric emptying into the duodenum. How does glucose differ from protein?

After a meal about bow much food does the stomach contain?
What is the rate of emptying gastric contents to the duodenum?

How do liquids/solids differ? Isotonic/hypotonic/hypertonic?

What size must particles be to enter the duodenum?

Answer 2

Slide 4
After a meal, the stomach contains about 1.5L of material (solid, liquid, secretions).

Emptying of the gastric contents to the duodenum is slow – takes ~3hours.

Liquids empty more rapidly, but solids empty after a log phase.

Isotonic contents empty more rapidly than either hypotonic or hypertonic contents.

Solids must be reduced to particles of

Question 3

Gastric emptying happens after…

4 factors

Answer 3

An increase in tone (intraluminal pressure) in the proximal portion of stomach

Increased strength of antral contractions

Opening of the pylorus so the contents can move

Simultaneous inhibition of duodenal segmental contractions.

Question 4

What happens to gastric emptying as the meal enters duodenum?

Describe the nature of the chyme and the neural response as it enters the duodenum.

What serves to decrease the strength of antral contractions? What else results in they pylorus and proximal gastric motility?

What is the net result?

What happens as chyme moves further down small intestine?

Answer 4

As meal enters the duodenum, it initiates feedback inhibition of gastric emptying.

This involves both neural and hormonal pathways based on the nature of chyme.

Vagal afferents respond to nutrients (H+ and hyperosmotic content) of chyme as it enters duodenum.

Reflex activation of vagal efferent outflow decrease the strength of antral contractions, contracts the pylorus, and decreases proximal gastric motility.

The net result is an inhibition (slowing) of gastric emptying.

As chyme moves further down the small intestine, the feedback inhibition is reduced- gastric emptying starts again.

Question 5

What are the two major factors that contribute to inhibition or slowing of gastric emptying?

Answer 5

The presence of fat in the duodenum

The presence of H+ (low pH) in the duodenum.

Question 6

What mediates the effect of fat?

Answer 6

The effect of fat is mediated by Cholecystokinin (CCK) – secreted when fatty acids are present in the duodenum.

Question 7

What is the effect of CCK?

Answer 7

CCK slows gastric emptying – pylorus contraction, to ensure that there is adequate time for fat to be digested and absorbed.

CCK also regulates gallbladder contraction, relaxation of sphincter of Oddi and pancreatic secretion.

Question 8

What mediates the effect of H+?

What do H+ receptors in duodenal mucosa detect?
What is the effect?

Answer 8

The effect of H+ is mediated via reflexes in the enteric nervous system.

H+ receptors in the duodenal mucosa detect low pH of chyme and relay this to gastric smooth muscle via interneurons in the myenteric plexus.

This reflex ensures that gastric contents are delivered slowly to the duodenum, so ample time is available for neutralization of acid by pancreatic HCO3-.

This neutralization is critical for pancreatic enzymes to function properly.

Question 9

Describe the exocrine pancreas’ contributions toward digestion process.

What are the components of the pancreatic secretion? Describe each.

Answer 9

It secretes about 1L of fluid per day into the lumen of duodenum (10 times its weight).

Pancreatic secretion has two components:
An aqueous component, high in HCO3-
An enzymatic component.

The HCO3- - containing aqueous component neutralizes the H+ delivered to the duodenum from incoming chyme.

The enzymatic component is enriched with enzymes that digests carbohydrates, proteins and lipids into absorbable molecules.

Question 10

Draw/describe the anatomy of the gall bladder and the ducts.

Answer 10

Slide 11.

Question 11

Describe the structure of pancreatic exocrine glands:

endocrine pancreas
exocrine pancreas

Answer 11

Endocrine pancreas – islets of Langerhans (2% of pancreatic volume): insulin, glucagon, somatostatin (inhibitor of G stomach cells), pancreatic polypeptide;

Exocrine pancreas – (90% of pancreatic volume) - Secretion of enzymatic and aqueous components.

Question 12

Describe how the exocrine is organized. What does it consist of? Describe each component.

Answer 12

Slide 16.
The exocrine pancreas is organized very similar to the salivary glands – consists of ducts and acini.

The acinus – is the blind end of a branching ductular system – lined by acinar cells.

The acinar cells secrete the enzymatic component.

The ducts are lined with ductal epithelial cells, which extend into a region of centroacinar cells in the acinus.

The centroacinar and ductal cells secrete the aqueous component

Question 13

Draw a model of the pancreatic secretions (ducts/acinus) Which are stimulated by CCK or secretin?

Answer 13

Slide 17.

Question 14

What regulates pH?

Describe the role of secretin. When is it released? What does it stimulate?

How does release stop?

Answer 14

Flow chart slide 18
The ducts are the effector arms of a pH regulatory system.

When luminal pH is below ~4.5, the S cells (in the small intestinal epithelium) are triggered to release Secretin.

Secretin then stimulates secretion of bicarbonate – results in increase of pH in the intestinal lumen.

This then produces negative feedback to stop secretin release.

Question 15

What is the second messenger of secretin? What is the downstream effect? Describe.

What is the net result?

Answer 15

Slide 19
Secretin increases cAMP in duct cells.

This opens the CFTR Cl- channels and an outflow of Cl- into the duct lumen.

This drives the antiporter that exchanges chloride ions for bicarbonate.

H+ is transported into blood by Na+ -H+ exchanger (NHE-1).

Net result
Secretion of HCO3- in the lumen
Absorption of H+, acidification of pancreatic venous blood

Question 16

What are the two courses for bicarb?

Answer 16

Two sources for bicarbonate:
Some taken across basolateral membrane via symporter NBC-1 (Na-bicarbonate cotransporter type 1).

Some generated intracellularly by carbonic anhydrase.

Question 17

What is Cystic fibrosis? Explain why pancreatic function is defective in this disease.

Answer 17

A genetic disease that affects function of various epithelial organs – lung, intestine, biliary system and pancreas.

In cystic fibrosis, CFTR (cystic fibrosis transmembrane conductance regulator) is mutated (inactive).

As a result, the bicarbonate secretory process is defective – CFTR not functional.

This results in a decrease in pancreatic ductal secretion, high concentration and precipitation of the acinar enzymes in the duct - ultimately destroying gland.

This explains why pancreatic function is defective in this disease.

Question 18

Describe control of pancreatic acinar secretion by CCK.

What type of cell releases CCK?

What stimulates these cells?

Draw.

Answer 18

Slide 21

CCK release from I cells (in the small intestinal epithelium) is triggered by:

Direct interaction of fatty acids or amino acids or both with I cells themselves.

Binding of fatty acids or amino acids or both to sensor paracrine cells that release CCK-RP (CCK-releasing factor or peptide).

By the release of monitor peptide by pancreatic acinar cells.

Question 19

What are the two ways by which CCK stimulates pancreatic acinar secretion?

Draw a diagram.

Answer 19

Slide 22
As an endocrine factor and binds to acinar cell CCK1 receptor.

It also stimulates neural reflexes that impinge on the pancreas – activates vagovagal reflex that leads to the release of ACh, GRP and VIP by pancreatic enteric neurons.

Question 20

By what mechanism do CCK, Ach, and GRP act?

What does stimulation of acinar cells lead to?

What is the effect?

Answer 20

Slide 23
CCK, ACh and GRP acts via mobilizing intracellular Ca++ .

The secretory products here are already pre-synthesized and stored in granules (zymogen granules).

Stimulation of acinar cells leads to phosphorylation of various regulatory and structural proteins.

This moves the granules closer to the apical membrane, where they fuse with plasma membrane.

Granular contents are released into the lumen (exocytosis) – and subsequently washed by ductal secretions.

Question 21

Summarize the main pathways for stimulation of pancreatic secretions in cephalic phase, gastric phase, and intestinal phase.

Answer 21

Slide 26

Question 22

Describe bile. What is it? Where is it synthesized and secreted?

Where is it stored?

What does in help digest/absorb?

What factor stimulates contraction of gallbladder and relaxation of sphincter of Oddi.

Answer 22

Another important digestive juice that is mixed with chyme in the small intestinal lumen is bile.

Bile is synthesized and secreted by hepatocytes into the bile canaliculi that drain into the bile ducts.

It is stored and concentrated in the Gallbladder.

Bile helps in the digestion and absorption of lipids.

CCK stimulates the contraction of Gallbladder and relaxation of Sphincter of Oddi.

Question 23

Describe the major constituents of bile.

Describe the structure. What do they form and why?

Answer 23

Major constituents of bile:

Bile acids – 65%
Phospholipids (mainly lecithins = PC) – 20%
Proteins – 5%
Cholesterol – 4%
Bile pigments (bilirubin for example) – 0.3%
Electrolytes (similar and isotonic to plasma) – 5-6%

Bile acids are detergents and form micelles.

These micelles shield the hydrophobic products of lipid digestion from the aqueous environment of lumen.

Question 24

What is enterohepatic circulation?

Can conjugated bile acids cross intestinal epithelial lining?

When are conjugated bile acids reabsorbed? How?

Answer 24

Flow chart slide 29

Majority of bile acid pool is recycled from the intestine back to the liver – via enterohepatic circulation.

Conjugated bile acids are unable to passively cross the intestinal epithelial lining.

When chyme reaches the terminal ileum and lipid absorption is completed, conjugated bile acids are reabsorbed by a symporter known as apical Na+ -dependent bile acid transporter (asbt).

A minor fraction of bile acids enters the colon –become deconjugated and is reabsorbed passively.

Question 25

Describe the motility of the small intestine.

What is mixed in the lumen?

What purpose does contractility of small intestine serve?

What are the two contractile activities that exist in the small intestine?

Answer 25

In the lumen of the small intestine we now have pancreatic and biliary secretions mixed with chyme.

The contractile activity of the small intestine allows the fragmentation of chyme into smaller pieces- exposing their surfaces to enzymes and detergents.

This increases the biochemical reactions significantly yielding small molecules that can be absorbed by the intestinal mucosa.

Contractile activity also propels the bolus for absorption of nutrients, water and ions.

Two contractile activities exist in the small intestine:
Segmentation
Peristalsis

Question 26

Where do segmentation contractions occur?

What is the purpose? Where does chyme go?

Answer 26

Segmentation contractions occur predominantly in the small and large intestine.

These allow mixing of the luminal contents with GI tract secretions and increase exposure to the mucosal surfaces where absorption occurs.

A small section contracts, splitting the chyme, sending it in both orad and caudad directions.

This section then relaxes allowing chyme to merge – this serves to mix chyme but produces no forward movement.

Question 27

Describe peristaltic contractions. Where do they occur?

What happens to chyme? How?

Answer 27

Peristaltic contractions occur in the pharynx, esophagus, gastric antrum, small and large intestine.

These contractions help to propel the chyme along the GI tract.

Here a contraction occurs at a point orad to the bolus, simultaneously, the portion caudad to the bolus relaxes; the chyme is thus propelled in the caudad direction.

Question 28

What is responsible for pattern of muscle segmentation?

What regulates each orad and caudad contractions in peristaltic contractions?

Answer 28

Bursts of highly localized action potentials in circular muscle are responsible for the pattern of muscle segmentation.

In Peristaltic contraction:

Orad contraction is regulated by acetylcholine and Substance P

Caudad relaxation is regulated by VIP and nitric oxide.

Question 29

Describe the migrating motor complex (MMC) during fasting in the small intestine.

When do these contractions occur? What hormone is involved?

What does this look like on a graph?

Answer 29

Slide 35
MMC in the duodenum and jejunum from a fasting human subject.

These are periodic contractions- mediated by the hormone motilin.

These occur at 90 min intervals – to clear any remaining gastric and intestinal contents out into the colon.

After a meal, motilin levels fall, MMC is suspended.

Question 30

Describe the following histological features of small intestine.

Brunners glands
Lieberkuhn glands
Paneth cells

Answer 30

Brunner glands: cells secreting mucus and Bicarbonate. is found in the submucosa of the duodenum. Its main physiological function is the secretion of alkaline-based mucus to protect the duodenal lining from the acid secreted in the stomach.

Lieberkühn glands: also Lieberkühn crypts,
secrete peptidases and enzymes that
digest carbohydrates.

Paneth cells reside at the bottom of villi and secrete antimicrobial peptides and enzymes (ribonuclease, esterases, etc.).

Question 31

Describe the villi and crypts in small intestine.

What three structures increase the absorption area?

Answer 31

Small intestine (long villi; short crypts)

Long and thin Villi

Absorption area increases because of:
Simple columnar epithelium with brush border (~3000 microvilli/cell)

Villi

Plica circularis in jejunum

Thus all 3 structure increase area to several hundred fold (600 fold) for a total area of 200 m2

Question 32

How can a secretin test be used to diagnose Zollingers Syndrome? How?

Answer 32

gastrinoma-gastrin prod. tumors. usually located in pancreas. prod. gastrin but these are not pancreatic or gastric cells but have property of both of them, have property of gastric cells bc secrete gastrin but location in pancreas and respond to secretin. normally gastric cells don’t respond to secretin (bc secretin receptors in ductal cells) but bc these cells in pancreas they may have secretin receptors. and these cells v sensitive to secretin test. if gastronoma and do secretin test gastrin goes way higher than normal.

Question 33

How is CCK inhibited?

Answer 33

when trypsin has digested food… then more and more trypsin available to digest monitor peptide and release peptide (and then we don’t need them anymore) so trypsin will digest those and CCK release will be inhibited.
trypsin (proteolytic enzyme) capable of breaking down enzymes . during active phase of digestion when plenty of proteins to work on, less trypsin diverted to these peptides so these peptides protected and go on stimulating CCK. when trypsin finished digesting protein then it will go digest monitor peptide and CCK-RP and CCK release will be inhibited

Question 34

How can a gallstone lead to pancreatitis?

Answer 34

gall stone in that area where bile duct meets pancreatic duct- problem w bile secretion and pancreatic secretion … (then enzymes build up and get pancreatis)

Question 35

If someone had surgery of terminal ileum what problems may arise? What might you see in the stool?

Answer 35

so people w surgery of terminal ileum they will have problems w bile absorption. no asbt activity so bile acids more and more lost in feces. lose bile acids so liver senses that and tries to prod. more and more but not efficient process. so their lipid digestion is compromised. will have fatty stools, etc.