L11- Gastroduodenal Secretions & Control Flashcards

1
Q

Gastric Secretions

A
  • HCl
  • Intrinsic factor
  • Pepsinogen
  • Mucus
  • Bicarbonate
  • Gastrin
  • Histamine
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2
Q

Secretions of Gastric Cell Types

A

A. Surface Epithelial Cells

  • Secretes mucus and an alkaline fluid (bicarbonate)
  • Protects epithelium from mechanical injury & gastric juice

B. Neck Mucous Cells

  • secretes mainly mucus, some pepsinogen

C. Chief (Peptic) Cells

  • secretes pepsinogen

D. Parietal (Oxyntic) Cells

  • Secretes HCl & Intrinsic Factor

E. Enterochromaffin-Like Cells

  • secretes histamine

F. D-cells

  • secretes somatostatin

G. G-cells

  • mainly pyloric glands
  • secretes gastrin
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3
Q

Functional Anatomy of the Stomach

A

A) Cardiac glandular region

  • secretes mucus

B) Proximal/body (80%)

  • oxyntic gland mucosa
  • parietal, chief and mucous neck cells
  • Secretes HCl, Intrinsic factors, pepsinogen

C) Pylorus Distal (Antral, 20%)

  • Pyloric gland mucosa
  • Mainly Gastrin & Mucous cells, few chief cells, almost no parietal cells
  • Secretes gastrin, small amount of pepsinogen, mucus
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4
Q

Rate of secretion of gastric juice

A

Rate of secretion controlled by endocrine, neural and paracrine signals.

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5
Q

Property and ionic composition of gastric juice

A
  • Gastric juice is isotonic to plasma
  • pH ranges about 2-3
  • Ionic composition various with the rate of gastric secretion
  • Basal rate: primarily NaCl
  • Increase [H+] [Cl-] with incease in secretion rate
  • Basal rate greater at night, lowest in early morning
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6
Q

Gastric Acid Functions

A
  • Converts inactive pepsinogen to active pepsin
  • Provides optimal pH for pepsin activity
  • Denatures ingested protein
  • Breaks up cells & connective tissue
  • Bacteriostatic
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7
Q

Intracellular mechanism of HCl secretion

A

The followings occur in parietal cells:

1) Intracellularly, CO2 and H2O react to form carbonic acid, catalyzed by Carbonic anhydrase (high concentration in parietal cells)
2) Carbonic acid then dissociates into H+ ion and HCO3-
3) The bicarbonate ions move out of the parietal cells on the capillary side, in exchange for chloride ions through an exchange pump
4) Cl- released on lumneal side
5) Intracellular H2O, on the other hand, breakdown into Hydrogen ion and hydroxide ion
6) Hydrogen ion produced by breakdown of water then secreted into the lumen by primary active transport and exchange pump
7) Hydroxide ions formed from water are neutralized by combination with hydrogen ions generated from CO2 and H2O

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8
Q

Control of Gastric acid secretion

A

STIMULANTS

Paracrine - Histamine

  • Histamine released from ECL cells
  • Act on H2 receptors on parietal cells
  • Strongest stimulant of HCl secretion

Neurocrine - vagal stimulation

  • Depends on neural input from vagal nerve
  • ACh acts on muscarinic receptors (M1 in ECL cells, M3 in parietal cells)
  • Stimulates release of HCl by parietal cells; histamine by ECL cells; (gastrin by G-cells?)

Endorcine - Gastrin

  • Secreted by G cells
  • Stimulates histamine release and synthesis by ECL cells
  • Trophic effects on ECL cells
  • Stimulates acid secretion by parietal cells via CCKB receptors

INHIBITOR

Somatostatin

  • inhibits gastric secretion
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9
Q

Secondary messengers in gastric acid secretion control

A

Histamine (Paracrine)

  • Histamine binding with H2 receptor will activate adenylyl cyclase, leading to increase in cAMP

Vagal Nerve (Neurocrine)

  • Acetylcholine binding with muscarinic receptors will lead to IP3, increasing intracellular calcium ion concentration [Ca2+] i

Gastrin (Endocrine)

  • After gastrin binding with CKKB receptor, intracellular calcium concentration will increase

Increased Calcium ion & cAMP concentration will activate protein kinase.

Ultimately these intracellular secondary messagers will control the transfer of H+/K+-ATPase (aka Proton Pumps) from cytoplasmic vesicles to plasma membrane, where it can allow the secretion of H+

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10
Q

Drugs targeted to reduce gastric acid secretion

A

1) H-2 receptor blockers

**- **Tagamet (cimetidine)

  • Zantac (ranitidine)
  • Pepcid (famotidine)

2) Proton pump inhibitors (PPI)

  • Prilosec (omeprazole)
  • Nexium
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11
Q

Antrectomy

A

Antrectomy (distal gastrectomy) is a procedure in which the portion of the stomach distal to the antrum is excised.

Before availability of effective antacid drugs, this is used to treat hypersecretion of HCl as it will remove majority of the G cells in antrum. Leading to decreased gastrin release and reduced HCl secretion

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12
Q

Gastrinoma

A

A tumor in the pancreas or duodenum that secretes excess of gastrin. There is hypersecretion of the HCl acid into the duodenum leading to ulceration. Excessive HCl acid production also causes hyperperistalsis, and inhibits the activity of lipase, causing severe diarrhea.

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13
Q

Functional Phases of Gastric Secretion

A

1) Cephalic Phase
2) Gastric Phase
3) Intestinal Phase

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14
Q

Cephalic Phase of HCl Secretion stimulation

A

Stimuli: Chewing, swallowing, taste and smell of food

-> Vagal impulse excite enteric secretomotor neurons to parietal, G and ECL celss

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15
Q

Gastric Phase of HCl Secretion stimulation

A

Stimuli:

1) Gastric distension (-> Local and vagovagal reflexes stimulate parietal cells and release of histamine and gastrin)

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16
Q

Intestinal Phase of HCl Secretion stimulation

A
  • Contributes about 10% of total secretion
  • Due to some G cells extending from antrum to duodenum
  • The most important aspect of intestinal phase is feedback regulation and inhibition
  • Involves feedback regulations between duodenal content & duodenal hormones including secretin & CCK (cholecystokinin)
  • These hormones have effect on pancreas, liver, gall bladder and stomach

Stimuli:

1) Peptides or amino acids in blood or lumen (–> Release gastrin from G cells in stomach)
2) Protein digestion products in duodenum (–> Release gastrin from G cells in intestine and enterooxyntin
3) Distension of duodenum (–> Enteric and vagovagal reflex to ECL, G and parietal cells)

17
Q

Regional inhibition of gastric acid secretion

A

Important in balancing the secretory activity of stomach with the digestive & absorptive capacities of the small intestine:

A) Stomach Oxyntic gland area

1) stimulated by: Acid (pH < 3)
- Mediated by: Somatostatin (D-cells)
- Effect: Inhibits acid secretion by parietal cells

B) Stomach antrum

1) stimulated by: Acid (pH < 3)
- Mediated by: Somatostatin (D-cells)
- Effect: inhibits gastrin release by G-cells

C) Duodenum

1) stimulated by: Acid
- Mediated by:

i) Secretin
- Effect: inhibits gastrin and acid release

ii) Nervous relfex
- Effect: inhibits acid secretion

2) Stimulated by: Hyper-osmotic solutions
- Mediated by: unidentified enterogasteron
- Effect: inhibits HCl secretion

D) Duodenum & Jejunum

1) stimulated by: Fatty acids
- Mediated by:

i) GIP (Gastric inhibitory polypeptide)
- Effect: inhibits gastrin and acid release

ii) Unidentified enterogasteron
- Effect: inhibits acid secretion

18
Q

Enteric Reflexes vs Vagovagal Reflexes

A

(?)

Enteric/short Reflexes: A series of nerve circuits that carry signals from one region of GIT, to sympathetic ganglia, and back to the gut wall

Vagovagal Reflexes: from GIT to afferent nerve fibres of CN X, from afferent nerves to autonomic centre in medulla, then through efferent nerve fibres of CN X to GIT

19
Q

Pepsinogen and Pepsin

A
  • Pepsinogen has no digestive activity
  • At intragastric pH < 5, pepsinogen is converted into active pepsin by cleavage of acid-labile linkages
  • Pepsin catalyses further conversion of pepsinogen to pepsin
  • Pepsin splits interior peptide bonds
  • Pepsin may digest up to 20% of protein in a typical meal
  • Pepsin most active at pH about 3
20
Q

Control of Pepsinogen Secretion

A

Stimulated by:

  • ACh from vagus or enteric nerve plexuses

When gastric acidity <3, feedback inhibition of acid on:

  • Gastric secretion of acid & pepsinogen
  • Gastrin production
  • ** Functions to prevent peptic ulceration & maintain optimal pH for enzyme action
21
Q

Secretion of Mucus and Bicarbonate (Source, function)

A

Source:

  • Mucus secreted by mucous neck cells of gastric glands & surface epithelial cells of stomach and duodenum
  • Bicarbonate secreted by surface epithelial cells

Function:

  • Forms a physical and alkaline barrier (i.e. Gastric mucosal barrier) on stomach surface protecting the mucosa against acidic, proteolytic gastric secretion
  • Maintain a almost neutral pH at stomach surface
  • Prevent peptic ulceration & maintain optimal pH for enzyme action
22
Q

Effect of Adrenergic agonists on gastric secretions

A

Adrenergic agonists decrease HCO3- secretion, leading to stress ulcers

23
Q

Effect of NSAIDs to gastric secretions

A

NSAID inhibits mucus & HCO3- secretion, prolonged use cause peptic ulcers and gastritis

24
Q

Secretion of Intrinsic Factor (Nature & Regulations)

A
  • Glycoprotein secreted by parietal cells
  • Regulation of secretion same as that of HCl as they both involves parietal cells

STIMULANTS

Paracrine - Histamine

  • Histamine released from ECL cells
  • Act on H2 receptors on parietal cells
  • Strongest stimulant of HCl secretion

Neurocrine - vagal stimulation

  • Depends on neural input from vagal nerve
  • ACh acts on muscarinic receptors
  • Stimulates release of HCl by parietal cells; histamine by ECL cells; (gastrin by G-cells?)

Endorcine - Gastrin

  • Secreted by G cells
  • Stimulates histamine release and synthesis by ECL cells
  • Trophic effects on ECL cells
  • Stimulates acid secretion by parietal cells via CCKB receptors

INHIBITOR

Somatostatin

  • inhibits gastric secretion
25
Q

Functions and Deficiency of Intrinsic factors

A
  • Required for absorption of Vitamin B12 at ileal mucosa
  • Vitamin B12 required for DNA synthesis & RBC maturation
  • Absence of intrinsic factor leads to vitamin B12 deficiency & megaloblastic anaemia
  • Pernicious anaemia caused by autoimmunity against gastric parietal cells or intrinsic factor itself
  • Secretion of intrinsic factor is the one gastric function that is essential for human life
  • Patients with pernicious anaemia and total gastrectomy require lifetime parenteral replacement of Vitamin B12
26
Q

Possible causes for reduced B12 absorption

A

1) Decreased intrinsic factor secretion
2) Inflammatory bowel disease leading to reduced ileal mucosa for B12 absorption

27
Q

Secretions of Small Intestine

A

 Mucus & bicarbonate from Brunner’s gland in duodenum: mucus protects duodenal wall from digestion by highly acidic gastric juice; bicarbonate neutralizes acid

 Mucus from intestinal globet cells: lubricates & protects the intestinal surface

 Aqueous isotonic fluid from enterocytes: important for dissolution and absorption of nutrients

 Digestive enzymes from enterocytes on villi: digestion of small peptides, dissacharides and lipids

 Control of secretion mainly by local enteric reflexes; hormones are also involved e.g. secretin, CCK