gastric secretion I

what is the function of the stomach?

1. stores food for 2-4 hours

2. secretes gastric juice → HCl, pepsinogen, intrinsic factor

3. allows controlled emptying of stomach contents into the small intestine

what is the function of the pyloric antrum?

the major area of endocrine secretion - production & release of gastrin

what is the function of the body of the stomach?

the major area of exocrine secretion

what is the histology of gastric glands?

• ~100 gastric pits per mm² of gastric surface - occupies ~50% of the total surface area

what is the structure of gastric exocrine glands?

• gastric glands:

  • surface mucous cell

  • parietal cell

  • enterochromaffin-like cell (histamine)

  • chief cell (pepsinogen)

• pyloric glands - antrum:

  • surface mucous cell

  • mucous neck cell

  • G cell (gastrin)

  • D cell (somatostatin)

what is the composition of gastric secretions?-

~2L gastric secretion/day, isotonic, pH 2-3

• HCl:

  • kills bacteria, denatures dietary protein, activates pepsinogen, cofactor for pepsin action

• pepsin:

  • initiates protein digestion

• intrinsic factor:

  • essential for Vitamin B12 uptake in lower ileum

what changes occur after eating?

• HCl acid secretion & changes in gastric pH after eating

where is HCl produced?

Parietal cell

• plasma - production of H+ incl involvement of carbonic anhydrase

• lumen - H+/K+ ATPase pump at membrane, K+ recycled at luminal membrane (alkaline tide)

  • PPI - omeprazole

what changes occur in the parietal cell during secretion?

50-100 fold increase in canalicular surface area

where is pepsinogen released & activated?

• made in chief cells

  • pepsinogen & HCl secreted into lumen

  • HCl converts pepsinogen to pepsin

what is the function of pepsin?

• an endopeptidase that initiates protein digestion

• responsible for about 15% of protein digestion

• a pH <2 is required for optimum proteolytic activity

how is intrinsic factor functioned and secreted?

• intrinsic factor is a glycoprotein secreted from parietal cells

• forms a complex with dietary B12 in the upper small intestine which protects it from enzymatic digestion

• the only gastric secretion that is essential for life as B12 is needed for maturation of erythrocytes and maintenance of CNS

• absense of intrinsic factor causes pernicious anaemia

how is vitamin B12 absorbed?

• occurs in the terminal ileum

• receptor mediated endocytosis

• only B12 is transferred to the blood

• in the circulation it is bound to a B12 binding protein

• excess B12 is stored in the liver

how is gastric secretion controlled?

gastric response to food ingestion involves:

• parasympathetic nerves

• endocrine hormones

• paracrine hormones

  • interactions between these systems at the parietal cells level

how is the gastric system autonomically controlled?

parasympathetic:

• increases secretion via direct and indirect mechanisms

sympathetic:

• no major control over secretion

enteric nervous system:

• submucosal and myenteric plexus secretion

what are the effects of increased parasympathetic nerve activity?

• HCl production

• pepsinogen release

• gastrin release

• mucous release

• gastric smooth muscle contraction

how is gastric secretion controlled by the endocrine hormones?

gastrin is the main endocrine hormone that promotes gastric secretion

it increases:

• HCl production

• pepsinogen release

• mucous release

other functions of gastrin:

• maintenance of gastric mucosal structure

• increases motility of GI smooth muscle

what paracrine hormones are involved in gastric acid secretion?

histamine

• stimulates HCl

• parietal cells forms

somatostatin

• inhibits HCl secretion

• direct effects on parietal cells forms

• inhibiting release of the positive regulators histamine & gastrin

what determines HCl secretion?

• PPIs (proton pump inhibitors) - omeprazole

• H2 receptor antagonists - famotidine

  • intracellular cAMP and Ca2+ levels determine HCl secretion.

what are the three phases of gastric secretion?

• cephalic phase - 30-35% of total secretion

• gastric phase - ~60% of total secretion

• intestinal phase - 5-10% of total secretion

describe the cephalic phase of gastric secretion.

• occurs before food enters the stomach

• short duration

function:

• prepares stomach for receiving food

stimuli:

• anticipation, sight, smell of food, chewing

components:

• direct - vagal stimulation and activation of submucosal plexus

• indirect - release of gastrin from g cells

describe the gastric phase of gastric secretion.

• occurs while the food is in the stomach

• long duration, 2-4 hrs

function:

• homogenise and acidify chyme, initiate digestion of proteins by pepsin

stimuli:

• distention, elevated pH and peptides and amino acids in the stomach

components:

• distention initiates a vago-vagal & enteric reflexes causing direct and indirect effects on parietal cells

• peptides cause secretion of gastrin

• NB: low luminal pH inhibits secretion

describe the intestinal phase of gastric secretion.

• occurs when chyme enters the duodenum

• largely hormonal

• long duration, hours

function:

• controls the rate of chyme entry into the duodenum

stimuli:

• duodenal stretch, presence of lipids and CHO and decreased pH

components:

• initial, short lived, stimulation of gastric secretion caused by gastrin release from G cells in duodenum in response to peptides in chyme.

• release of CCK and secretin have an inhibitory effect on acid secretion and gastric emptying

with all the acid during digestion, why doesn’t the stomach digest itself?

because of the gastric mucosal barrier

• 5 micrometer thicken during fasting

• 200 micrometer thick during digestive phase

• effectiveness reduced by:

  • aspirin

  • helicobacter pylori

  • leads to gastritis, ulceration

what is H+ secretion accompanied by?

• delivery of HCO3- into the perfuming blood (alkaline tide)

• this HCO3- is carried to the surface epithelium where it is secreted into the surface mucosal layer