1. Pathophysiology of Peptic Ulceration
Gastric Acid Secretion
Gastric Mucosal Barrier
Pathogenesis of Peptic Ulceration
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gastric secretion

2. Gastric Secretion Gastric juice HCl Electrolytes Mucus, Water
Intrinsic factor
Bicarbonate
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gastric secretion

3. Gastric Gland Gastric (oxyntic) gland
Gastric lumen
Gastric (oxyntic) gland
Surface epithelia cells (mucus cells)
Alkaline mucus- viscid
Mucous neck cells (neck chief cells)
Soluble mucus
pepsinogen
Columnar mucus cells
Mucous neck cell
Parietal cell
Peptic cell
From Physiology Book by H.T. Sherrief
27-Apr-17
gastric secretion

4. Gastric Gland Parietal cells (oxyntic cells) Hydrochloric acid
Gastric lumen
Parietal cells (oxyntic cells)
Hydrochloric acid
Intrinsic factor
Chief [peptic] cells (zymogen cells)
Pepsinogen
Columnar mucus cells
Mucous neck cell
Parietal cell
Peptic cell
From Physiology Book by H.T. Sherrief
27-Apr-17
gastric secretion

5. Gastric Gland Enterochromaffin cells Specialized cells serotonin
Gastric lumen
Enterochromaffin cells
serotonin
Histamine
Specialized cells
vasoactive intestinal peptide (VIP)
Substance P
Glucagon
Columnar mucus cells
Mucous neck cell
Parietal cell
Peptic cell
From Physiology Book by H.T. Sherrief
27-Apr-17
gastric secretion

6. Gastric Gland Parietal cell Produce a solution containing
Gastric lumen
Parietal cell
Produce a solution containing
Approx. 160 mmol of HCl/l; pH 0.8 (H+ conc. = 3 to 4 million time that in plasma)
Energy cost = 1500 calories/l of HCl
Columnar mucus cells
Mucous neck cell
Parietal cell
Peptic cell
From Physiology Book by H.T. Sherrief
27-Apr-17
gastric secretion

7. Gastric Gland Parietal cell
Gastric lumen
Intrinsic factor (vit. B12 - R factor binding macromolecule)
Parietal cell
Also produce
Gastric lipase
Gastric amylase
Gelatinase
Columnar mucus cells
Mucous neck cell
Parietal cell
Peptic cell
From Physiology Book by H.T. Sherrief
27-Apr-17
gastric secretion

8. Gastric Gland Chief cells
Gastric lumen
Chief cells
Produce small volume of electrolyte similar to ECF
Contain Pepsinogen( PG I, PG II)
Some individuals secrete ABO blood group antigen in their gastric juice
Columnar mucus cells
Mucous neck cell
Parietal cell
Peptic cell
From Physiology Book by H.T. Sherrief
27-Apr-17
gastric secretion

9. Pyloric Gland Similar structure like the oxyntic gland Have G-cells
Gastric lumen
Similar structure like the oxyntic gland
Contain few peptic (chief) cells
No parietal cells
Contain mucus cells
Have G-cells
Columnar mucus cells
Mucous neck cell
G-cells
Peptic cell
From Physiology Book by H.T. Sherrief
27-Apr-17
gastric secretion

10. Pyloric Gland secrete G cells produce Gastrin
Gastric lumen
secrete
Mucus and electrolytes
G cells produce Gastrin
Peptic cells produce pepsinogen
Columnar mucus cells
Mucous neck cell
G-cells
Peptic cell
From Physiology Book by H.T. Sherrief
27-Apr-17
gastric secretion

11. HCl Secretion Function of HCl
Participates in the breakdown of proteins
Provide optimal ph for pepsin
Hinders growth of pathogenic bacteria
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gastric secretion

12. Mechanisms of HCL Secretion
Chloride ions are actively secreted into lumen of canaliculi
Against concentration gradient
creates a negative potential -40 to -70 mv in canaliculi
passive diffusion of K+, Na+
KCl, NaCl
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gastric secretion

13. Mechanism of Acid Secretion
The H+ conc. In parietal cells
3 to 4 million fold higher than in blood
Cl- is secreted against
Concentration and electrical gradient
Ability of parietal cell to secrete acid
Dependent on active transport
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gastric secretion

14. Mechanism of Acid Secretion
Key player in acid secretion
H+/K+ATPase or “proton pump”
Mg++ dependent
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gastric secretion

15. Mechanisms of Acid Secretion
Dissociation of H2O
H2O  H+ + OH -
The H+ is then actively secreted into the lumen by active pump in exchange of K+
Proton pump
H+/K+ ATPase
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gastric secretion

16. Mechanism of Acid Secretion
Na+ is actively reabsorbed by a separate pump
Thus most of the Na+, K+ that had diffused into canaliculi
Reabsorbed into the cell
H+ take their place
Giving strong soln of HCL
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17. Mechanism of Acid Secretion
The OH - combine with CO2 to form HCO3-
Carbonic Anhydrase
The HCO3 - diffuses to ECF and into blood
Alkaline tide
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gastric secretion

18. Mechanism of Acid Secretion
H2O passes through cell and into canaliculi by OSMOSIS
Final secretion from the canaliculi contain
HCL at a conc of 150 to 160 mEq/l
KCl at conc of 15 mEq/l
Small amount of NaCl
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gastric secretion

19. CO2 CO2 H20 CO2 + OH- H+ HCO3- HCO3- K+ H+ K+ K+ K+ Na+ Na+ K+ K+ Na+
Cl-
Cl-
Cl-
H20
H20
H20
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gastric secretion

20. Pepsinogen Secretion Precursor of pepsin Produced by the Chief Cells
Stored in secretory granules
Vagal stimulation, Histamine, Gastrin
Cause preformed granules to be released into lumen
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gastric secretion

21. Intrinsic Factor Mucoprotein Essential for vitamin B12 absorption
Secreted by parietal cells
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gastric secretion

22. Control of Gastric Acid Secretion
Basal secretion
During fasting gastric juice secretion occurs
Postprandial
Cephalic, gastric and intestinal phases
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gastric secretion

23. Cephalic Phase Before food gets into the stomach
Sight , smell, thought, taste, hunger,appetite center
Cause reflex stimulation of gastric secretion
This phase of secretion
Accounts for 20% of total gastric secretion associated with eating a meal
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gastric secretion

24. Gastric Phase Presence of food in the stomach excite
Stretch receptors, chemoreceptors
Local enteric reflexes
gastrin production
All these lead to stimulation of gastric secretion
Gastric phase of secretion
Account for 70% of total gastric secretion associated with eating a meal
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gastric secretion

25. Intestinal Phase Presence of food in the intestines
Release of Gastrin by duodenum
Continue to stimulate secretion of some gastric juice
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gastric secretion

26. Control of Gastric Acid Secretion
Neural mechanisms
Stimulation of vagus
Stimulates intramural plexuses
Which then stimulates PARIETAL, CHIEF, MUCUS cells
Neurotransmitter is Acetylcholine
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gastric secretion

27. Control of Gastric Acid Secretion
Vagal stimulation increases secretion by
Stimulating histamine releasing cells
Histamine then diffuses to stimulate parietal cells
Vagal stimulation activates antral G – cells
Produce Gastrin
Gastrin acts on parietal and chief cells
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gastric secretion

28. Control of Gastric Acid Secretion
Humoral
Gastrin
Secreted by G - cells
Peptide G34, G17
G17 more abundant and potent than G34 for acid secretion
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gastric secretion

29. Control of Gastric Stimulation
Stimulus for Gastrin secretion
Vagus
Secretagougues (AA,peptides, alcohol,caffeine,Ca++
Distension of stomach
Gastrin release intracellular Ca++
promote proton pump
Cl- channel insertion
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gastric secretion

30. Control of Gastric Acid Secretion
Histamine
Enterochromaffin cells
Mast cells
Acts on H2 receptors
Increases cAMP
This then promote proton pump function
increases H+ secretion
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gastric secretion

31. Control of Gastric Acid Secretion
H2 receptor blockers
Cimetidine etc
Prostaglandin E1, E2 inhibit histamine release
Pentagastrin stimulates HCl and Gastrin release
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gastric secretion

32. + + - - + - + + Ach Gastrin Histamine Somatostatin ECL Cells D- Cells
H2 receptor
Histamine
ATP - +
Adenyl cyclase -
D- Cells
cAMP +
Prot kinase K+
Somatostatin H+
G - Receptor
 Ca++
Ach - Receptor +
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gastric secretion

33. Inhibition of Gastric Juice Secretion
Acidity of gastric juice to pH <3.0
Gastrin mechanism is blocked
Enterogastric reflex
Presence of food in SI
Distension, acidity, FA, AA
Secretin, cholecystokinin
Oppose stimulatory effect of Gastrin
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gastric secretion

34. Enterogastric Reflex CCK GIP gastric inhibitory peptide
Initiates enterogastric reflex
Slows gastric emptying
Inhibit gastric secretion
GIP gastric inhibitory peptide
Inhibit Histamine
VIP vasoactive Intestinal peptide; somatostatin
Have moderate inhibitory effects on gastric secretion
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gastric secretion

35. Gastric Mucosal Barrier
Protect the gastric lining cells from
Damage by intra-luminal HCL
Autodigestion
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gastric secretion

36. Gastric Mucosal Barrier
Compact arrangement of epithelial cells with TIGHT JUNCTION
Epithelial cells secrete bicarbonate (under influence of prostaglandin)
Thick layer of adherent MUCUS (alkaline mucus) 1 mm thick
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gastric secretion

37. Gastric Mucosal Barrier
Regenerative capacity of mucosa
Trophic effect of Gastrin
High turn over rate:
Entire mucosa replaced within 3 days
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gastric secretion

38. Peptic Ulcer Peptic ulcer is a mucosal lesion of Gastric acid & pepsin
Stomach (gastric ulcer)
Or duodenum (duodenal ulcer)
Gastric acid & pepsin
Play major pathogenic role
Helicobacter pylori infection
Play a major role as well
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gastric secretion

39. Peptic Ulcer
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gastric secretion

40. Peptic Ulcer Peptic ulcer also include
Gastric ulcers & duodenal ulcers associated with
Stress
Ingestion of drugs
Aspirin, NSAIDS
Gastrin producing tumours
Zollinger – Ellison syndrome
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gastric secretion

41. Peptic Ulcer Thought to result from imbalance between
Aggressive factors
Protective factors
Aggressive factors
Protective factors
Gastric mucus, bicarbonate, prostaglandins, blood supply
Acid & pepsin H. pylori, irritation, aspirin, NSAIDS
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gastric secretion

42. Helicobacter Pylori Infection occurs in about
95% of patients with duodenal ulcers
75% to 85% of patients with gastric ulcers
The infection is also found in
25% of people without peptic ulcers
Thus other factors
Must be present to trigger ulcer formation
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gastric secretion

43. Helicobacter Pylori Spiral shaped bacillus Gram negative
Acid
Gastric lumen
Spiral shaped bacillus
Gram negative
Penetrate mucus layer
Adheres to luminal surface of gastric epithelial cells
Does not invade the gastric mucosa
pH2
mucus
pH 7
H. Pylori
Parietal cell
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44. Helicobacter Pylori Thrives in highly acid environment
Produces urease enzyme
For ammonia formation
Neutralize the acid
Produces a number of toxins
Cause inflammation & damage to epithelium
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gastric secretion

45. Helicobacter Pylori Produces proteases & phospholipases
Degrade the glyco-lipid complex of mucus gel
 The thickness of mucus gel
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gastric secretion

46. Helicobacter Pylori Stimulate chronic gastritis associated with
Depletion of somatostatin from d-cells
Gastric release from G-cells
Stimulate acid production
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47. Other Pathogenic Factors
DU patients as a group
Secrete more acids than normal individuals
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gastric secretion

48. Other Pathogenic Factors
Some DU patients have
True G cell hyperplasia
G cell hyperfunction or
Increased sensitivity of parietal cells to stimulation
Increased capacity to secrete acid and pepsin
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gastric secretion

49. Other Pathogenic Factors
However, some patients with DU secrete normal amount of acid. May be
Secrete abnormal mucus
Failure of protective barrier
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gastric secretion

50. Other factors Gastric emptying Stress and DU Accelerated
More acid is being delivered to duodenal bulb than in normal
Stress and DU
Emotions and anger increase GASTRIC ACID and PEPSIN secretion
Smocking
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gastric secretion

51. Other factors Renal failure Severe Burns Increased incidence of DU
Have high level of circulating Gastrin
Severe Burns
Develop stress ulcers (curling Ulcers)
? Hypergastrinaemia
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gastric secretion

52. Other Factors Zollinger – Ellison syndrome
Excessive production of Gastrin from islet cell tumor (Gastrinoma)
Hyper-secretion of gastric acid
Rapid recurring ulceration despite therapy
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gastric secretion

53. Physiological Basis of Treatment
Helicobacter pylori eradication
Successfully prevents relapses
Eliminate need for
The long term therapy
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gastric secretion

54. Physiological Basis of Treatment
Treatment regiment include
Proton pump inhibitor
Taken together with 2 antibiotics
Amoxicillin + metronidazole
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gastric secretion

55. Physiological Basis of Treatment
Antacids
Widely available for self medication
Relief of minor dyspepsia
Majority of drugs based on
Combinations with
Calcium, aluminium, magnesium salts
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56. Physiological Basis of Treatment
However, have side effects
Calcium compound
Cause constipation
Magnesium compounds
Cause diarrhoea
Aluminium compounds
Block absorption of other drugs
Digoxin, tetracycline
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gastric secretion

57. Physiological Basis of Treatment
Histamine – H2 receptor antagonists
Competitive inhibition of histamine at H2 receptor on parietal cell
Cimetidine, ranitidine
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gastric secretion

58. Physiological Basis of Treatment
Proton pump “H+/K+ ATPase” inhibitor
Irreversible inhibition of “H+/K+ ATPase” pump in the parietal cell
 Gastric acid production
Most powerful inhibitor of
Gastric acid secretion
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59. Achlorhydria and Hypo-secretion
Hypo-secretion of gastric acid
Usually when acid is not secreted pepsin is also not secreted
Correlate with histological lesions and the extent of gastritis
Gastric atrophy
Complete failure of gastric secretion
ACHLORHYDRIA
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peptic ulcers

60. Type A Gastritis Associated with possible parietal cell antibodies
Diffuse involvement of mucosa
Little or no gastric acid secretion
Familial occurrence
Associated with pernicious anaemia
Intrinsic factor
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peptic ulcers

61. Type B Gastritis More common than type A
Parietal cell antibodies are absent
Gastric mucosa and antrum may be involved
Acid secretion is only moderately impaired
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62. Hypo-secretion
Occurring as a result of gastritis or by use of H2 receptor blockers
May lead to bacterial overgrowth
Production of Nitrosamine
Has been implicated in the pathogenesis of gastric cancer
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peptic ulcers