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Flashcards in GI V & VI Deck (57):
1

Describe the major functions of the stomach.

2 main functions, secretions

The major functions of the stomach are: (storage and motility)
Storage: temporary storage of meal

Secretion of H+: killing microorganisms and conversion of pepsinogen → pepsin

Secretion of Intrinsic factor (IF): essential for the absorption of vitamin B12

Secretion of mucus and HCO3- : protection of gastric mucosa

Secretion of water: lubrication of bolus, suspension of nutrients in solution

Motor Activity: mixing secretions (H+ and pepsin) with bolus.

Coordination of motor activity of smooth muscle and emptying of stomach contents into duodenum.

2

Describe the importance of the following secretions in the stomach:

H+
Intrinsic factor
mucus and HCO3
water

Secretion of H+: killing microorganisms and conversion of pepsinogen → pepsin

Secretion of Intrinsic factor (IF): essential for the absorption of vitamin B12

Secretion of mucus and HCO3- : protection of gastric mucosa

Secretion of water: lubrication of bolus, suspension of nutrients in solution

3

What would happen if one underwent gastric surgery? What would be the effect (in regards to gastric secretions?)

intrinsic factor is req for vit. b12 absorption which really happens further in intestine but factor required for absorption is intrinsic factor (synthesized in stomach)

gastric surgery- lose intrinsic factor so bc not synthesized elsewhere in body, those ppl will have problems w vitamin b12 absorption.

4

Describe the regulation of motor and secretory responses in the stomach. Provide examples for neural, endocrine, and paracrine.

Regulation of both motor and secretory responses are via:

Neural: Intrinsic and extrinsic

Paracrine: histamine is a powerful stimulator of H+ secretion.

Endocrine:
gastrin (stomach and duodenum)- stimulates gastric acid secretion.

somatostatin (stomach, duodenum, and pancreas) - inhibits gastric secretion.

5

Describe the importance of somatostatin.

imp. negative regulator of acid secretion (negative feedback system) when pH drops, acid secretion, then drop of pH stimulates somatostatin which will inhibit further secretion. neg. feedback

6

Describe the functional anatomy of the LES and cardia.

What is the region? Luminal secretion? Motility?

LES and cardia (LES part of esophagus)

luminal secretion: mucus and bicarb

motility:
-prevention of reflux
-entry of food
-regulation of belching

7

Describe the functional anatomy of the fundus and body of stomach.

Luminal secretion? Motility?

Luminal secretion:
H+
Intrinsic factor
mucus
HCO3-
pepsinogens
lipase

Motility:
-reservoir
-tonic force during emptying

8

Describe the functional anatomy of the antrum and pylorus.

Luminal secretion? Motility?

luminal secretion: mucus and HCO3-

motility: mixing, grinding, sieving, regulation of emptying

9

What are the three regions the stomach is divided into?

What are the 2 functional parts the stomach is divided into (to discuss physiology)?

The cardia
The corpus (or fundus, body)
The antrum

The proximal part (closer to mouth) (thin wall)

The distal part (further away from mouth). (thick wall)

10

Describe gastric pits and glands.

Slide 8
The lining of the stomach contains columnar epithelium – folded into gastric pits.

Each gastric pit is the opening where gastric glands empty.

Note in Pylorus:
Long pits and short
glands

gastric pit- columnar epithelial cells, in pits have openings where diff glands we find will empty their contents and now transported into lumen
surface epithelial cells -careful to protect those cells or else they are eroded (like we can see in esophagus)

11

The gastric mucosa is divided into three distinct regions based on the gland structure. Describe.

Small cardiac glandular region (below LES) – primarily mucus and HCO3- - secreting gland cells, that provide mechanical and chemical protection of the gastric mucosa

The remaining portion of the gastric mucosa is divided into:
Oxyntic or parietal gland region (fundus)
Pyloric gland region (antrum).

12

Describe the 6 types of secretory cells the fundus and antrum contain.

parietal or oxyntic cells

mucuous neck cells

peptic or chief cells

enterochromaffin-like cells

D cells

G cells

13

What do parietal or oxyntic cells secrete?

HCl: kills bacteria, allows activation of pepsin from pepsinogen, low pH for effective pepsin action.

HCl (hydrochloric acid): H+ activates pepsinogen into pepsins.

Intrinsic factor: glycoproteins that bind vitamin B12 making it absorbable by the ileum mucosa. It is an ESSENTIAL FACTOR!

Intrinsic Factor: glycoprotein, required for normal absorption of vitamin B12 in the ileum.

14

What do mucous neck cells secrete?

Mucus: protection of gastric mucosa.

Bicarbonate [HCO3]- + MUCUS : important for protection of gastric mucosa against acidic and peptic luminal environment.

15

What do Peptic or Chief cells secrete?

Pepsinogens: In acidic environment they are cleaved into pepsins (mixture of various proteases). Pepsins are only active in ACIDIC environments.

Pepsin initiates protein digestion in the stomach (20%) but that is not essential.

Pepsinogen: is the inactive proenzyme of pepsin.

16

What do ECL cells secrete?

Histamine (paracrine): most powerful stimulator of HCl secretion;

17

What do D cells secrete?

Somatostatin (endocrine) - powerful inhibitor of HCl secretion.

18

What do G cells (pyloric region) secrete?

Gastrin (endocrine): HCl secretagogue.

19

In the gastric juice (The cells of the gastric mucosa secrete a fluid called Gastric Juice) what is the only essential component?

In a healthy human, intrinsic factor is the only essential component of gastric juice, the functions of other components are redundant.

20

Describe how the parietal cell is different when resting vs active.

Slide 18

Resting parietal cell cytoplasm contains numerous tubules and vesicles – tubulovesicular system, their membranes contain transport proteins needed for secretion of H+ and Cl-. Intracellular secretory canaliculi are present.

Once activated, the tubulovesicular membranes fuse with the plasma membrane of the secretory canaliculi – (increases the number of H+-K+ antiporters on the secretory canaliculi membrane) – and opens to the lumen of the gland.

21

Describe the blood, lumen, and intracellular gastric parietal cell.

What is the combination of all events?

In the intracellular fluid: Carbonic anhydrase produces H2CO3 from CO2 + H2O.
-H2CO3 then dissociates into H+ and HCO3-.

In the Lumen (or apical membrane): H+ is secreted via the H+-K+ ATPase – active process that transports both H+ and K+ against electrochemical gradient (uphill).

-Cl- follows H+ by diffusing through Cl- channels.
-Increased intracellular Ca++ and cAMP increase luminal conduction of Cl- and K+.

In the basolateral membrane: HCO3- is absorbed into the blood via Cl- - HCO3- exchanger.

Combination of all these events leads to a net secretion of HCl and net absorption of HCO3-.

22

What does omeprazole do?

In the Lumen (or apical membrane): H+ is secreted via the H+-K+ ATPase – active process that transports both H+ and K+ against electrochemical gradient (uphill). This is inhibited by the drug omeprazole- used to treat ulcers to reduce H+ secretion.

23

What is alkaline tide?

In the basolateral membrane: HCO3- is absorbed into the blood via Cl- - HCO3- exchanger. This absorbed HCO3- is the reason for the “alkaline tide” (high pH) in gastric venous blood after a meal. This HCO3- is eventually secreted back in the GI tract by the pancreas.

24

What ions do surface epithelial cells of stomach secrete?

Which ion concentrations are higher or similar to plasma?

The surface epithelial cells of stomach also secrete a watery fluid that contains Na+, Cl-, K+ and HCO3-.

Although Na+, Cl- concentrations are similar to plasma, the K+ and HCO3- concentrations are higher.

This HCO3- is entrapped by the viscous mucus that coats the stomach lumen – together forms the mucosal barrier.

25

Decribe mucus, and intact mucin structure. Which part is susceptible to pepsin activity? What are the implications for this?

Slide 23
Mucus- Secretions containing mucins are viscous and sticky – collectively called mucus.

Secreted by mucus neck cells.

They are ~80% carbohydrate.

Intact mucins are tetramers of 4 similar monomers, 500 KD each.

The central portion of the mucin tetramer, near the disulfide crosslinks is susceptible to proteolytic digestion by pepsins.

Proteolytic fragments do not form gels – dissolves the protective mucus layer.

26

Why doesn't H+ and pepsin corrode the stomach surface?

Mucus and HCO3- protects the surface of the stomach from H+ and pepsins.

good defense mechanism in mucus layer w bicarb thats why don't see gastric ulcer on regular basis
how gastric cells reproduce acid in stomach area-how cells are protected. defense of mucus layer as long as mucin activity is high and can form this thick mucus gel the epithelial cells are okay..

27

What forms the gastric mucosal barrier?

The protective mucus layer on the luminal side and the alkaline secretions trapped within this – form the gastric mucosal barrier – protects gastric mucosa.

The mucus layer (~0.2mm thick) – separates the HCO3- -rich secretions of the surface epithelial cells from the acidic contents of the gastric lumen.

28

What is the strongest stimulant for gastric H+ secretion?

What else will be secreted?

Parasympathetic stimulation via vagus nerve is the strongest stimulant for gastric H+ secretion. Extrinsic efferent fibers terminate on intrinsic neurons that innervate:
Parietal cells, ECL cells, G cells.

Vagal stimulation also secretes pepsinogen, mucus, HCO3- and intrinsic factor.

29

What three substances stimulate H+ secretion by parietal cells?

Which has a different second messenger?

Acetylcholine (neurocrine)
Histamine (paracrine)
Gastrin (endocrine)

Histamine has diff second messenger (cAMP) others have Ca and IP3

30

Describe Ach. From where is it released? What does it bind to? Second messangers? What inhibits its effects?

-released from vagus nerve innervating the gastric mucosa

-binds to muscarinic (M3) receptors on the parietal cells-

-2nd messengers are – IP3/Ca++ - stimulates H+ secretion

-Atropine (inhibits muscarinic receptors) blocks Ach effects on parietal cells.

31

Describe histamine. From where is it released? What does it bind to? Second messangers? What inhibits its effects?

-released from gastric ECL cells – paracrine effect on parietal cells

-binds to H2 receptors

-2nd messenger cAMP – stimulates H+ secretion by parietal cells

-Cimetidine blocks H2 receptors – blocks histamine effect.

32

Describe gastrin. How is it secreted into circulation? What does it bind to? What second messengers?

-Secreted into circulation by stomach G cells – endocrine effect on parietal cells

-Binds to cholecystokinin B (CCKB) receptors on the parietal cells

-The 2nd messengers are IP3/Ca++.

33

What is potentiation?

The rate of H+ secretion can be regulated by each of these independently as well as by interactions among the three – this is called potentiation – the reason is unclear - might be due to the fact that each agent works via a different receptor and in case of histamine via a different 2nd messenger.

34

Histamine potentiates the actions of Ach and gastrin...what will cimetidine do?

block direct histamine effects
block histamine-potentiated effect of Ach and gastrin.

35

Ach potentiates the actions of histamine and gastrin- atropine will ...

block the direct effects of Ach
block Ach-potentiated effects of histamine and gastrin.

36

Describe the stimulation of gastric acid secretion by drawing the effects of Ach, Gastrin, Histamine, somatostatin, and prostaglandins.

Slide 30

37

How much HCl secretion takes place in cephalic and oral phase?

What are the stimuli?

What are the direct and indirect mechanisms that promote HCl secretion during the cephalic and oral phases?

30% of total HCl secretion

stimuli are smelling, tasting, chewing, swallowing and conditioned reflexes (in anticipation of food).

Several mechanisms that promote HCl secretion during this phase:

Direct stimulation of the parietal cells by vagus via Ach (muscarinic receptors) – neural effect.

Indirect stimulation of the G cells by vagus via GRP (Gastrin-releasing peptide) to produce gastrin- endocrine effect.

Indirect stimulation of the ECL cells by vagus (Ach) and gastrin (CCKB receptors)- to produce histamine- paracrine effect

slide 32.

38

What proportion of total HCl secretion takes place in the gastric phase?

What is the stimuli?

What 3 additional mechanisms exist?

60% of total HCl secretion

Stimuli are distension of stomach, presence of amino acids, small peptides.

All the mechanisms that are present in cephalic, oral phase also operate here.

Two additional mechanisms exist:
1) distension of the stomach activates vagovagal reflexes – stimulate gastrin release.

2) A direct effect of amino acids and small peptides on G cells - stimulate gastrin release.

3) Alcohol and caffeine also stimulate HCl secretion.

39

What percent of HCl secretion takes place in intestinal phase? What is it mediated by?

Only 10% of total HCl secretion and is mediated by products of protein digestion.

40

Describe the feed-back inhibition.

Acidic chyme in the distal stomach (antrum) initiates a negative feedback loop – inhibits acid secretion.

When the pH of lumen is below 3, somatostatin (SS) is released (by endocrine cells) – inhibits via direct and indirect pathways:
In direct pathway, SS binds to receptors in parietal cells – inhibits stimulatory effect of histamine.

In indirect pathway, SS inhibits - histamine release from ECL cells and gastrin release from G cells.

Prostaglandins – inhibit stimulatory effect of histamine.

41

What can be a long term side effect of hyper-secretion/patients treated for GERD with proton pump inhibitors?

proton pump inhibitors for people w hyper-secretion. GERD. must control acid secretion. use proton pump inhibitors

people not really prod. acid so pH drop not there
so expect that negative feedback not there… means somatostatin.

kind of problem (not in terms of acid secretion.. medicine are effective for GERD) secondary effect tho bc long term prod. of gastrin…indirect way somatostatin inhibits acid secretion by inhibiting G cells so no gastrin release …this not happening so as result, gastrin secretion not controlled in these patients. so long term their gastrin levels are really high. usually not problem

42

Describe the digestion that occurs in the stomach. When might the digestion action in stomach be important?

Some digestion occurs in the stomach, but it is not required.

Pepsin digests proteins (20%) but that is not essential;

Some amylase digestion in the stomach occurs. Amylase is inactive at low pH but not when the active site is occupied by carbohydrates (substrate protection). Yet, that digestion is not important;

The digestion of lipids start in the stomach (10%)- Gastric Lipases attach to the surface of lipid droplets – generates free fatty acids and monoglycerides, but this is not essential.

However, in pancreatic disorders the action of gastric lipases may be important.

43

Describe the 2 regions of the stomach.

Orad (proximal)- contains fundus, proximal part of body – thin walled.

Caudad (distal) – contains distal part of the body and antrum – thick walled.

Contractions in the caudad region (generated by strong muscles) mix the food and propel it into the small intestine.

44

What is receptive relaxation? How does it occur?
Describe the innervation. Describe neurotransmitter released.

Distension of the lower esophagus by food causes relaxation of LES – also relaxation of the orad stomach - called receptive relaxation.

This is via vagovagal reflex- mechanoreceptors detect stomach distension, relay this to CNS via sensory neurons. CNS sends efferent information to smooth muscle of orad stomach to relax.

Neurotransmitter released from postganglionic peptidergic vagal fibers is VIP.

45

Describe mixing and digestion in caudad region. Where do waves of strong contraction begin?

What is retropulsion?

Caudad region- waves of strong contraction start in the mid portion of stomach – move distally towards pylorus, increasing in strength towards pylorus.

They mix the gastric contents and periodically propel a portion of these in the duodenum through pylorus- followed by closure of pylorus.

Much of the chyme (not emptied into duodenum) is propelled back to stomach for further mixing and break-down – this is known as retropulsion.

46

Describe the gastric phase of gastric motility.

Describe the sensory receptors, intramural plexuses.

What is initiated to control acid secretion?

What effect will parasympathetic innervation have, excitatory or inhibitory? Describe what det. the rate of antral contractions and magnitude of contractions.

Is pylorus closed or open in gastric phase? What is the purpose of the antral contractions?

Sensory receptors (stretch and receptors sensitive to aminoacids and small peptides) in the gastric mucosa connect directly to intramural plexi.

Intramural plexuses connect with sensitive vagal fibers leaving the stomach. Vagovagal Reflexes are initiated to control acid secretion, distension of gastric wall, and gastric motility.

Parasympathetic innervation via vagus nerves is excitatory (Ach and substance P) in the lower stomach causing ↑ motility (strong smooth muscle contractility); the rate of antral contractions is set by gastric pacemaker, but the magnitude of contractions is regulated by neural input.

In the gastric phase, pylorus is usually closed, the antral contractions mix the gastric contents and reduce size (grinding function).

47

Describe gastric emptying. Draw graph glucose vs protein.

After a meal how much material does the stomach contain?

Describe the pace of emptying of gastric contents. How do liquids differ from solids? Isotonic/hypotonic/hypertonic contents?

To what amount must solids be reduced to enter duodenum?

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

48

Describe the pylorus. What does it consist of?

Pylorus consists of a two ring-like thickenings of circular smooth muscle cells;

49

Describe the coordination of contraction/relaxation in the gastroduodenal junction.

Coordination of contraction/relaxation follows the general rule in the GI tract: antrum contracts while initial portion of duodenum relaxes.

50

What are the functions, control, and common pathologies of gastroduodenal junction.

Functions:
-Filtering large size particles of food
-Emptying gastric content at a rate consistent with duodenum’s ability to digest chyme
-Prevention of reflux of bolus into stomach;

Control by hormonal, paracrine and nervous factors.

Common pathologies - include gastric ulcerations (gastric mucosa is sensitive to bile – basic pH) and duodenum ulcerations (intestinal mucosa is sensitive to gastric secretion- acid pH).

51

What happens if pylorus is not working properly? Why?

if pylorus not working working properly bile can reflux back into gastric area… can cause ulcers, gastric mucosa not designed for alkaline pH

52

Describe the control of the pyloric muscle tone.

Describe significant hormonal effects, parasympathetic and sympathetic innervation..

What are vagal excitatory and inhibitor fibers and responses?

Slide 47

53

What is peptic ulcer disease? How is it caused?

Ulcerative lesion of gastric or duodenal mucosa.

This is caused by the erosive and digestive action of H+ and pepsin on mucosa.

Causes are
Loss of protective mucous barrier or other protective factors
Excessive H+ and pepsin secretion or other damaging factors
A combination of both.
Based on location, peptic ulcers can be gastric or duodenal.

54

What are some protective and damaging factors contributing to peptic ulcer disease?

protective factors:
-HCO3- and mucus
-prostaglandins
-mucosal blood flow
-growth factors

damaging factors:
-H+ and pepsin
-H pylori
-NSAIDs
-stress
-smoking
-alcohol

55

Describe gastric ulcers:

Why do they form?
What results?
What is a major causative agent?
How is net H+ secretory rate and secretion of gastrin affected?

Forms primarily because of defects in the mucosal barrier.

This allows H+ and pepsin to digest a portion of the mucosa.

Major causative agent is gram-negative bacteria H. pylori.

They release cytotoxins (e.g. cagA toxin) that destroys the protective barrier and cells underneath.

Surprisingly, in these patients, net H+ secretory rates are lower and thus the secretion rate of gastrin is increased (lacking the negative feedback).

56

Describe duodenal ulcers.

More common than gastric ulcers and form because H+ secretory rates are higher.

Excess H+ delivered to the duodenum overpowers the buffering capacity of pancreatic HCO3-.

This excess H+ combined with pepsin damages the duodenal mucosa.

57

What is Zollinger-Ellison Syndrome?

What is the effect?

What is treatment?

In these patients usually a tumor (or gastrinoma) located in the pancreas – secretes high quantities of gastrin.

High gastrin produces two direct effects:
Increased H+ secretion by parietal cells
Increased parietal cell mass

The excess H+ produces duodenal ulcer.

This also leads to steatorrhea (fatty stool), since low duodenal pH inactivates pancreatic lipase.

Gastrin secretion by the tumor does not undergo feedback inhibition by H+ (as normal gastrin secretion), so gastrin levels continue to increase.

Treatment includes
inhibitors of H+ secretion – e.g. Cimetidine, Omeprazole
Surgical removal of tumor.