Secretory Functions of the GIT

Question 1

Functions of the secretory glands of the GIT

Answer 1

1. Secretion of digestive juices, which starts the process of assimilation of nutrient intake.
2. Mucous glands, from the mouth to the anus, provide mucin for lubrication and protection of all parts of the GIT.

Question 2

Stimulation of the secretion of secretory substances:

Four mechanisms which causes glands of the GIT to secrete juices.

Answer 2

1. Local epithelial stimulation especially of the secretion of mucin by mucous cells - a direct mechanical stimulation of the surface of glandular cells by food molecules.
2. Local neurogenic stimulation through the enteric nervous system -via chemoreceptors with direct mechanical stimulation by food molecules, or via stretch receptors with distention of the gut wall.

The resulting nervous reflexes stimulate both the mucous cells and other secretory glandular cells.

3.Central neurogenic stimulation via parasympathetic
nerves is the major pathway of control in the upper GIT.

4.Local hormonal stimulation of glandular secretion in especially the stomach and small intestine help regulate the volume and character of the secretions - local gastro-intestinal hormones are polypeptides
or polypeptide derivatives.

Question 3

Gastric Secretions and the three types of gastric Glands

Answer 3

Oxyntic

Cardiac

Pyloric

Question 4

Name the three cell
types present in the
gastric glands
and list their
secretions.

Answer 4

The surface epithelium and gastric pits are lined with mucin-secreting columnar cells.

The majority of cells in the cardiac and pyloric glands are also mucous, specialised for the secretion of mucin glycoproteins.

Cardiac: Mucin

Pyloric: Mucus and Gastrin( G cells)

The cells in the gastric (or oxyntic) glands are secreting either HCl, mucus or pepsinogen, or intrinsic factor.

Note: G cells, lying in-between the mucous cells of the pyloric (or antral) glands, secrete the
hormone gastrin into the portal circulation - they are, therefore, enteroendocrine cells.

Question 5

What do stimulated parietal cells secrete?

Answer 5

Stimulated parietal cells secrete an HCl solution of about 160 mM into the lumen of parietal canaliculi, which is isotonic with the body fluids. The pH of this acid is about 0.8 - extremely acidic!

Question 6

Discuss the formation of HCL(10)

Answer 6

Water becomes dissociated into H+ and OH in the cytosol.

The protons are then actively
transported against an enormous concentration gradient into the lumen of the canaliculi in
exchange for luminal K+: a specific proton pump, H+,K+
-ATPase, catalyses this active exchange process.

K+ is accumulated within the cell by the Na+,K+-ATPase in the basolateral membrane. Potassium ions move down their electrochemical gradient, leaking through conductance channels on both canalicular and basolateral membranes.

A Cl-/HCO3-antiport in the basolateral membranes transports Cl from the extracellular fluid
into the parietal cell in exchange for HCO3-, which leave the cell down a concentration gradient.

The chloride ions then move by passive diffusion via conductive channels into the lumen of the canaliculus, giving a strong solution of H+Clin the canaliculus.

Water passes into the canaliculi by osmosis because of the accumulation of ions in the canaliculi.

Thus, the final secretion contains a hydrochloric acid solution of 0.16 N, which moves outward through the open end of the canaliculi into the lumen of the gland.

An important step is that CO2, either formed during metabolism in the cell or entering the cell
from the blood, combines under the influence of carbonic anhydrase (CA) with OH to form
bicarbonate ions necessary to increase the rate of the Cl-/HCO3-antiport.

Therefore, the movement of Cl from the blood to the lumen against its electrochemical gradient is achieved due to excess OHin the cell after H+ has been pumped out.

Drugs that bind to the gastric H+, K+-ATPase (proton pump inhibitors - PPI, such as omeprazole, or lansoprazole) give effective inhibition of HCl secretion.

Question 7

Pepsinogen

Answer 7

Secreted: Mucous cells as well as peptic(chief) cells

Activation: When in contact with Hydrochloric acid and by previously activated pepsin-split to smaller molecule

Function:

Environment: Highly acidic medium, 1.8-3.5 pH

Question 8

Intrinsic Factor(IF)

Answer 8

Secreted: Oxyntic/Parietal Cells

It is essential for Vit. B12 absorption

Absence: Pernicious Anaemia-Gastric atrophy

IF binds vit.b12 in stomach-Protecting it from destruction in small intestines»IF binds with receptors in ileum and vit. b12 is absorbed

NO IF-Not vit. b12 to mature red blood cells in the bone marrow.

Question 9

Regulation of Gastric Secretion

Answer 9

1. Neurogenic Mechanism

2. Hormonal Mechanism

Question 10

Neurogenic Mechanism for gastric stimulation and how acid secretion is brought about

Answer 10

Acetylcholine: excites secretion by all the secretory cell types in the gastric glands, including secretion:

1. Pepsinogen by the chief cells
2. HCl by the parietal cells
3. Mucin by the mucous cells.

Acid secretion in particular is increased by acetylcholine acting on M3 muscarinic receptors on the parietal cells to increase intracellular
Ca2+
.

Question 11

Hormonal Mechanism for gastric secretion

Answer 11

Both histamine and gastrin stimulate the secretion of HCL by the parietal cells.

1. Gastrin: Acts on parietal cells by binding on the gastric receptors to increase intracellular Ca2+.
2. Histamine: binds to the H2 receptors via Gs increases Adenylyl Cyclase(AC) activity which results in an increase of intracellular cyclic AMP.

Question 12

Control of HCL secretion

Answer 12

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Question 13

CONTROL OF HCL Secretion

Answer 13

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Question 14

control of hcl secretion

Answer 14

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Question 15

Where is Gastrin secreted from?

Answer 15

Secreted from G cells located in the pyloric glands in the antral mucosa.

G- cells lie in between the mucous cells of the pyloric/antral glands,secrete gastrin into the portal circulation

Small quantities are also secreted by the duodenal mucosa, pancreatic islets (foetal life), pituitary gland, and the central nervous system.

Question 16

Stimuli that increase gastrin secretion from the G cells include the
following:

Answer 16

Increased vagal discharge: non-cholinergic, probably GRP (gastrin releasing-peptide!). Probably initiated via antral luminal distention.

Luminal peptides and some free amino acids present in the chyme that reaches the antral stomach.

Antral luminal distention (local mechanical effect)

Question 17

Where is Gastrin released?

What are the functions of G-17 In physiological concentration

Answer 17

Released into the portal circulation to reach the fundus and body of the stomach.

Funtions:

1. Stimulation of gastric acid secretion by two mechanisms.

Gastrin binds directly to gastrin receptors (CCK-B receptors) present on the parietal cells.

CCK-B receptors are also present on the ECL(Enterochromaffin Like) cells,
and gastrin thus stimulates acid secretion indirectly via the release of histamine - this axis provides a potent effect on the production of HCl.

2. Stimulation of gastric motility.
3. Trophic action - causes increased proliferation of the mucosal epithelial cells.

(Its effect on contraction of the LES may only be in large doses.)

Question 18

Paracrine inhibitors:

Answer 18

Paracrine D cells release somatostatin, which inhibits gastrin
release from the G cells in the antrum as well as histamine release
from ECL cells in the oxyntic region.

Patients taking acetylsalicylate and other anti-inflammatory
drugs (NSAIDs) that inhibit prostaglandin synthesis by blocking
the cyclo-oxygenase (COX) enzymes have an increased
incidence of ulcers and subsequent upper gastrointestinal
bleeding. The normal inhibiting effect of PGE is absent.

Question 19

Paracrine inhibitors:

Answer 19

Paracrine D cells release somatostatin, which inhibits gastrin
release from the G cells in the antrum as well as histamine release
from ECL cells in the oxyntic region.

Question 20

Pharmacological effects of NSAIDS and Acetylsalicyclate

Answer 20

Patients taking acetylsalicylate and other anti-inflammatory drugs (NSAIDs) that inhibit prostaglandin synthesis by blocking the cyclo-oxygenase (COX) enzymes have an increased incidence of ulcers and subsequent upper gastrointestinal bleeding. The normal inhibiting effect of PGE is absent.

Question 21

Phases of control of gastric secretion rate

Answer 21

Both motility and secretory processes in the GIT are traditionally divided into three phases: a
cephalic phase, a gastric phase and an intestinal phase.

Question 22

Feedback inhibition of acid secretion during the gastric phase

Answer 22

The acidity of the chyme in the antral stomach plays an important role in feedback inhibition of gastric juices.

When the acidity increases to a
pH below 3.0, the secretion of gastrin by the G cells is blocked. (Most probably due to the fact that acid is a potent inhibitor of G cell proliferation and thus renewal).

A low pH may also cause an inhibitory
neurogenic reflex that inhibits oxyntic gland secretion.

This feedback inhibition by acid protects the gastric mucosa againstexcessive acidity and excessive proteolytic activity (high pepsin
concentration), which could promote peptic ulceration.

In addition, the feedback mechanism is also important in maintaining optimal pH for function of the peptic enzymes in the protein digestive process, which is a pH of about 3.0.

Question 23

Intestinal phase: inhibition of gastric secretion

Answer 23

The post-stomach intestinal factors that inhibit gastric secretion are similar to those inhibiting the motility of the stomach.

Revise the four duodenal factors mentioned on page 3/15:

 The degree of distention of the duodenum.

 The degree of acidity of the duodenal chyme.

 The presence of degraded proteins.

 Hormonal feedback inhibiting gastric secretion (mainly via CCK).

Question 24

Gastric mucosal barrier:

Answer 24

The cardiac and pyloric glands are structurally similar to the oxyntic (gastric) glands but contain
mostly mucous cells that are identical with the mucous neck cells of the oxyntic glands:

1. Together they all secrete large quantities of a very viscous and alkaline mucus.
2. Insoluble
3. Coats the stomach mucosa with a gel layer of mucus
   often more than 1 mm thick.
4. Providing a major shell of protection for the gastric mucosa against the highly acidic, proteolytic gastric juice.
5. Contributes to the lubrication of food transport.

Question 25

What is the Hollander Hypothesis

Answer 25

A two-component gastric barrier which protects the gastric epithelium against its own luminal acid and proteolytic enzymes-If damaged, gastric irritation develops leading to ulceration and consequent autodigestion

Question 26

What should the mucosa of the stomach and small intestine allow.

Answer 26

The mucosa of both the stomach and the small intestine has to allow efficient transport of
nutrients across the epithelium while rigorously excluding passage of harmful molecules and
micro-organisms. These exclusionary properties of the gastric and intestinal mucosa are
referred to as the “gastrointestinal barrier”.

Question 27

What does the two component hypothesis in the stomach include

Answer 27

It includes an intrinsic as well as a extrinsic barrier

Question 28

The intrinsic barrier:

Answer 28

The defense provided by the apical membranes of epithelial cells, and the tight junctions between the
epithelial cells. Continual cell renewal contributes to this intrinsic barrier.

Question 29

The extrinsic barrier:

Answer 29

Secreted mucin and HCO3
-that form a viscoelastic surface gel layer on the mucosal cells in a continuous sheet, with a pH of 7.0.

The role of gastric mucus is:
1. To prevent contact
between pepsin and the underlying mucosa.

2. To impede back diffusion of protons through the gel.
3. Stabilize an unstirred gel layer

Question 30

What may affect the integrity of the intrinsic barrier:

Answer 30

The integrity of the intrinsic barrier may be affected by a large number of endocrine and paracrine factors.

Question 31

Mention the cytokines which have the potential in barrier maintenance:

Answer 31

1. Epidermal growth factor (EGF)-secreted in saliva and from duodenal glands.
2. Transforming growth factor alpha (TGF-alpha)- secreted by gastric epithelial cells

Both peptides bind to a common receptor and stimulate epithelial cell proliferation and renewal
renewal.

Question 32

How can the gastrointestinal barrier be disrupted

Answer 32

By local infections by bacteria and viruses, exposure to toxins or physical insults, and a variety of systemic
diseases lead to its disruption.

Question 33

Discuss Helicabacter pylori

Answer 33

Helicobacter pylori exist solely in the juxtamucosal portion of the gastric mucus gel,
thriving in an alkaline* pH microenvironment.

Infection with H. pylori may degrade the gastric
mucous gel layer or damage the cell membranes.

It is therefore accepted that patients infected
with H. pylori have at least gastritis, and the infection may be involved in the pathophysiology of both gastric ulcer and duodenal ulcer disease.

H. pylori produces urease on its outer surface, resulting in the formation of NH4
+, alkalinizing its microenvironment.

Question 34

Discuss Ischemic injury and reperfusion

Answer 34

Damage to the gastrointestinal barrier due to ischaemic injury and reperfusion injury is a
common and serious condition.

Ischaemic injury occurs when blood flow is insufficient to deliver enough oxygen and nutrients necessary for maintenance of cell integrity.

Reperfusion injury occurs when blood flow is restored to ischemic tissue, but reactive free oxygen radicals
are generated within the mucosa, especially within the numerous local leukocytes activated during the course of the ischemic incident.

Question 35

What is meant by back diffusion of Acid

Answer 35

When the disrupted barrier permits H+ ions to penetrate into the gastric mucosa resulting in changes in the lamina propria