Secretion of GI

1. Secretory function
of Gastrointestinal tract

2. Salivary Secretion
Principal Salivary glands are
• Parotid glands : Serous glands ,watery secretion.
• Sublingual glands & Submandibular glands: secretes mixed serous & viscous
secretion.
Composition:
• varies with flow rate
• Average secretion -800 ml to 1500 ml daily
• pH between 6.0 - 7.0, optimum range for action of Amylase [ptyalin].
• 99% water & 1% solids [organic & inorganic substances],
• Organic substances : ptyalin , lingual lipase , lysozyme, kallikerin , small
amount of urea , uric acid , cholesterol & mucin.
• Inorganic substances : low level of Na+, Cl-, High level of K+ and HCO3–

3. Mechanism of Saliva Secretion
• Parotid gland [serous gland] innervated by
glossopharyngeal nerve [CN IX]
• Secretes water, electrolytes and enzyme [
nonviscous or serous secretion]
• Submandibular and sublingual [mixed gland]
innervation-Facial nerve [CN VIII]
• Viscous saliva rich in mucin glycoprotein
• Initial secretion is isotonic to plasma [Acinar
cells]
• Ductal cells modify primary secretion
• impermeable to water
• Increased absorption of Na+ and Cl-
• Secretion of K+ and HCO3-

5. Function of Salivary Secretion
• Salivary amylase for digestion of starch.
• Lingual lipase begins fat digestion.
• Also contain immunoglobulin A, lysozymes, thiocyanate,
lactoferrin, and HCO3− provide protective & cleansing function
• HCO3− helps to neutralize acid refluxed from the stomach and
inhibits dental cavity formation by neutralizing acid produced
by bacteria acting on food.

6. • Endocrine: Epidermal growth factor (EGF)
• Prevent tooth eruption,
• Facilitate maturation of the cellular lining of the gut, and
cytoprotection of the esophagus.
• Excretory: excretion of certain substances in saliva, produce certain
symptoms may indicate the presence of poisons or viruses in saliva
e.g. blue gums are diagnostic for lead poisoning.
• Lubrication: Mucins provide the lubrication needed to facilitate
speech and swallowing.
• Water balance: When body water tables are low, the mouth
becomes dry, stimulating thirst.
Function of Salivary Secretion

7. Regulation of salivary secretion
• Salivary glands are controlled mainly by
parasympathetic nervous signals from the
superior and inferior salivatory nuclei in the
brain stem.
• Salivary secretion is increased by
parasympathetic nervous stimulation [PNS]
• Sympathetic stimulation can also increase
salivation a slight amount, much less so than
does parasympathetic stimulation
• Food conditioning, taste & tactile sensation
through tongue, smell, nausea are stimulants
of salivary secretion-
• Dehydration, fear, sleep inhibit secretion.

8. Regulation of salivation
• Parasympathetic stimulation mediated by muscarinic receptor
• Cholinergic agonists increases secretion
• Anticholinergic drugs – inhibit secretion
• Salivation also increases due local gastric reflex initiated by irritable food-
protective mechanism [dilute the irritants]
• Copious salivation partly due to increased blood flow to the gland because of
• Parasympathetic nerve signals
• Vasodilator effect is caused by kallikrein secreted by the activated
salivary cells,
• Xerostomia- Dryness of the mouth caused by diminished function of the
salivary glands due to aging, disease, drug reaction

9. Major concepts
• Tonicity of primary and secondary secretion?
• Major cations and anions in saliva
• Activation of adrenergic α1 receptor increases enzymatic
secretion
• Factors affecting salivary secretion and effects of cholinergic
agonist and anticholinergic drugs
• For example:
• Myasthenia gravis

10. Gastric juice secretion
Stomach act as
• Holding area for food - waiting for digestion in small intestine
• Prepares food as chyme - for action of enzymes of pancreas and small
intestine
• Regulate release of chyme to small intestine
Composition
• 2-2.5L / day, Acidic pH 0.8
• Water 99.45% & solids 0.55% [electrolytes , enzymes, mucin, intrinsic
factor].
• Enzymes -pepsin, gastric lipase, gastric gelatinase, gastric amylase,
lysozyme , carbonic anhydrase.
• Organic substances : Intrinsic factor and Mucin.

11. Oxyntic glands also called gastric glands:
• located on the inside surfaces of the body and
fundus of the stomach, constituting the proximal 80
percent of the stomach.
• Secrete hydrochloric acid & intrinsic factor by
parietal or oxyntic cells, Pepsinogen by chief cell,
Histamine by Enterochromaffin-like (ECL) cells and
Mucus by mucus neck cells
Pyloric glands:
• located in the antral portion of the stomach, the
distal 20 percent of the stomach
• Secrete mucus and hormone gastrin- stimulate
secretion of HCl
• Other secreting cells:
• D cells : secretes somatostatin
Gastric juice secreting Cells

13. Formation of HCl by the Parietal Cell
• Basic stimulants for Gastric
Secretion Acetylcholine, Gastrin, and
Histamine
• Acetylcholine released by
parasympathetic stimulation excites
secretion of pepsinogen by peptic
cells, hydrochloric acid by parietal
cells, and mucus by mucous cells.
• Gastrin and histamine strongly
stimulate secretion of acid by parietal
cells but have little effect on the other
cells.
• Main driving force HCl secretion by
the parietal cells is a hydrogen-
potassium pump [H+-K+ ATPase].

14. Phases of Gastric Secretion

15. Regulation of HCl Secretion
• Direct action of Vagal stimulation- mediate via
M3 receptor-release H+
• Ach by vagus nerve also release Gastrin-
mediates its action on G cell via releasing
GRP
• Distension of stomach-release Ach- release
gastrin- release H+
• Protein rich food- release gastrin-release H+
• Gastrin also act on EC cells to release
Histamine, potentiates action of Ach to
release H+
• Gastrin- act on D cell to inhibit somatostatin
secretion
• Low pH: inhibit gastrin release [ feedback
inhibition]

17. Stimulation of Gastric Secretion

18. Inhibition of Gastric Secretion

19. Factors affecting of HCl Secretion

21. Factors inhibiting HCl secretion
• Enterogastric Reflex, initiated by distending the small bowel, by the
presence of acid in the upper inhibits stomach secretion also reduces
stomach emptying to already filled intestines
• The hormones such as secretin, gastric inhibitory peptide GLIP (glucose
like insulin peptide), vasoactive intestinal polypeptide, and somatostatin-
also have slight to moderate effects in inhibiting gastric secretion
released due to The presence of acid, fat, protein breakdown products,
hyperosmotic or hypo-osmotic fluids, or any irritating factor in the upper
small intestine
• Prostaglandins: inhibit HCl secretion and increases secretion of mucus
cell [mucin + HCO32-]

22. Regulation of Pepsinogen Secretion
• Occurs in response to two main types of signals:
• Stimulation of the peptic cells by acetylcholine released from the vagus
nerves or from the gastric enteric nervous plexus
• Stimulation of peptic cell secretion in response to acid in the stomach,
directly related to the amount of acid in the stomach.
• Loss the ability to secrete normal amounts of acid, results in decrease in
secretion of pepsinogen [chief cells are normal]
• CCK inhibit the secretion of pepsinogen by chief cells

23. Mechanism for the regulation of Gastrin
Release
• D cells located close to the G cells.
• D cell secretes somatostatin, acting as a
paracrine, inhibits gastrin release.
• Vagal stimulation release GRP at the G
cells, stimulating them directly to release
gastrin.
• Other inhibitory to the D cell, where they
release acetylcholine, which inhibits
somatostatin release.
• Distention or Digested protein act directly on
the G cell to stimulate gastrin release

24. ECL
P
G D
D
High Acid
in Antrum
High Acid in lumen

25. Effects of Abnormal HCl Secretion
• Pernicious anemia: in Atrophic gastritis, the person develops because of
failure of absorption of vitamin B12 stimulation in absence of intrinsic
factor [Gastritis results in achlorhydria -lack of stomach acid secretion]
• Zollinger–Ellison syndrome: Occurs when a gastrin-secreting tumor of
the pancreas causes increased gastrin- stimulating parietal cell to
secrete increased acid.
• High level of gastrin in this syndrome are non-physiologic i.e. not
regulated by feedback of increased acid content in stomach.
• Pentagastrin stimulation test – show no change in HCl production–
suggest gastrin-secreting tumor of the pancreas or gastrinoma

26. The Gastric Mucosal Barrier
• Complex system made up of submucosal,
epithelial and mucus elements, Protect the
stomach against hydrochloric acid and
noxious agents
• Pre-epithelial protection is made up by the
mucus-bicarbonate barrier, create a pH
gradient maintaining the epithelial cell
surface at near neutral pH.
• Rapid regeneration of damaged cells
• Prostaglandins maintain optimum blood
flow and prevent vascular endothelial
injury [adequate supply of nutrients and
removal of toxic agents]
• Epithelial layer is impermeable to HCl
• Tight junction impermeable to luminal fluid
containing H+

27. The Gastric Mucosal Barrier

29. Gastric ulcer
• An ulcerative lesion of the gastric or duodenal mucosa.
• Occurrence: due to imbalance between aggressive factors and mucosal
protective mechanisms.
Aggressive factors
• Pepsin secretion – excessive acid secretion due to Helicobacter pylori (H.
pylori), non -steroidal anti-inflammatory drugs (NSAIDs) [decrease the
secretion of the mucin and bicarbonate], stress, smoking and alcohol.
Protective factors:
• Prostaglandins (E2 & I2 )- decreases blood flow
• Mucus/bicarbonate secretion- neutralizes H+ ions of gastric secretion
• Mucosal blood flow- decreases blood flow
• Rapid turnover of gastric mucosa

30. H. Pylori and Gastric ulcer
• Damage of mucosal barrier due to excess H+ secretion attributed to
excessive response of gastrin to meal
• H.Pylori is gram negative bacteria with high activity of urease enzyme-
catalyzes the formation of ammonia from urea.
• NH3 + H+ [ pH of Gastric juice] form ammonium ions [NH4- damages the
epithelial cells of gastric mucosal barrier]
• Also increases parietal cell density- increases HCl production
• H.Pylori causes inhibition of somatostatin release
• Increased release of gastrin in response of meal
• Inhibit release of HCO3- [failure to neutralize H+ ions]

31. Diagnostic value for Duodenal Ulcer
wide variation in normal- basal level of acid 1-5 mEq/hour ,
maximal level 6-40 mEq/h.
In duodenal ulcer patient, rate of acid production: basal rate is
2-10 mEq/hour - maximal rate is 30-80 mEq/h]
a. Endoscopy: ideal
b. Gastrin level and rate of Acid production- misleading

32. Drugs that block gastric H+ secretion
• Atropine blocks H+ secretion by inhibiting cholinergic
muscarinic receptors on parietal cells, thereby inhibiting H+
secretion.
• Cimetidine: Block H2 receptor and thus inhibit binding of
histamine- thus reduces H+ ions secretion
• Omeprazole is a proton pump inhibitor directly inhibits H+ K+
ATPase and stops acid secretion.

33. • Which of the following can virtually stop secretion of
gastric acid during gastric phase?
a. Proton pump inhibitor
b. Antacids
c. Histamine receptor blocker
d. Antigastrin antibodies
e. Atropine

34. • Which of the following can virtually stop secretion of
Gastric acid during cephalic phase?
a. Antacids
b. Histamine receptor blocker
c. Antigastrin antibodies
d. Vagotomy
e. Sympathectomy

35. • What will be the effect of distension of stomach on
secretion of gastrin releasing peptide [GRP], gastrin,
and somatostatin level?

36. • Which of the following best describes the nature of
saliva produced at high flow rates?
a. Isosmotic fluid with ionic composition similar to plasma
b. Hypertonic fluid rich in NaCl
c. Hypotonic fluid rich in NaCl
d. Hypotonic fluid rich in KHCO3
e. Hypertonic fluid rich in KHCO3

37. • Which of the following substance, responsible for
damage of gastric mucosa barrier, increased by H.
pylori?
a. Bile salts
b. Gastrin
c. Pepsin
d. NSAIDS
e. Prostaglandins E2
f. Ammonium ions