Digestive system

STOMACH
• Gastric secretions
• Gastric emptying
• Mechanical and chemical
digestion in stomach
Stomach
 Gastric Juice
Tubular glands
• Oxyntic (gastric) glands
– HCl
– Pepsinogen
– Intrinsic factor
– Mucus
• Pyloric glands
– Mainly mucus
– Pepsinogen
– Gastrin (hormone)

The gastric glands secrete about 2500 mL of gastric juice daily.

Parietal (oxyntic) cells secrete HCl
& Intrinsic factor
Composite diagram of a parietal cell, showing the resting state
(lower left) and the active state (upper right).
The resting cell has
intracellular canaliculi (IC),
which open on the apical
membrane of the cell, and
many tubulovesicular
structures (TV) in the
cytoplasm. When the cell is
activated, the TVs fuse with
the cell membrane and
microvilli (MV) project into
the canaliculi, so the area of
cell membrane in contact
with gastric lumen is greatly
increased.
Mechanism of secretion of HCl
 In kidney H+ is transported into the tubular lumen by an
antiport in exchange for Na+. But in stomach H+ is secreted
into the gastric lumen in exchange for K+ by H+-K+ ATPase.
Regulation of gastric secretion
Acid secretion is increased by acetylcholine
acting on M3 muscarinic receptors to increase
intracellular Ca2+ and by gastrin acting on
gastrin receptors to increase intracellular Ca2+.
In addition, gastrin stimulates
histamine secretion by entero
chromaffin-like (ECL) cells, and
this is the principal way in which
gastrin stimulates H+ secretion.
Histamine binds to H2 receptors,
and via Gs, this increases adenylyl
cyclase (AC) activity and
intracellular cAMP. PGE2 acts via
Gi to decrease adenylyl cyclase
activity and intracellular cAMP.
Cyclic AMP and Ca2+ act via
protein kinases to increase the
transport of H+ into the gastric
lumen by H+-K+ ATPase.
 Peptic ulcer
• Helicobacter pylori - disrupts the barrier
• Aspirin and other NSAIDs - inhibit the production of
prostaglandins and consequently decrease mucus and HCO3–
secretion.
• Zollinger–Ellison syndrome, gastrinomas with tumors secreting
gastrin causes prolonged hypersecretion of acid.
• Inhibition of acid secretion – cimetidine - block the H2 histamine
receptors on parietal cells or omeprazole and related drugs that
inhibit H+–K+ ATPase.
• H. pylori can be eradicated with antibiotics, and NSAID-induced
ulcers - treatment with the prostaglandin agonist misoprostol.
• Gastrinomas can sometimes be removed surgically.
 Digestion in stomach
• Protein digestion begins in the stomach, where pepsins cleave the
bonds between aromatic amino acids such as phenylalanine or tyrosine
and a second amino acid.
• The pepsin precursors are called pepsinogens (proenzymes) and are
activated by gastric hydrochloric acid (pH optimum of 1.6-3.2).
• A gelatinase that liquefies gelatin is also found in the stomach.
• Stomach also secretes a lipase. It is of little importance except in
pancreatic insufficiency, but lingual lipase is active in the stomach and
can digest as much as 30% of dietary triglyceride.
• Intrinsic factor (IF) binds with Vitamin B12, but its absorption takes
place in ileum. Deficiency of IF leads to pernicious anemia.
 Gastric Motility
• Receptive relaxation of stomach – prepares ahead of time
to receive the food propelled down the esophagus during
swallowing.
• Mixing waves – weak peristaltic constrictor waves –
initiated by the basic electrical rhythm (slow waves) –
mainly helps along with retropulsion in mixing food with
gastric juice.
• Emptying of stomach – Pyloric pump
 Gastric Emptying
• In the regulation of gastric emptying, the antrum, pylorus, and
upper duodenum apparently function as a unit.
• Contraction of the antrum is followed by sequential contraction of
the pyloric region and the duodenum.
• In the antrum, partial contraction ahead of the advancing gastric
contents prevents solid masses from entering the duodenum, and
they are mixed and crushed instead.
• The more liquid gastric contents are squirted a bit at a time into the
small intestine.
• Normally, regurgitation from the duodenum does not occur, because
the contraction of the pyloric segment tends to persist slightly
longer than that of the duodenum.
• The prevention of regurgitation may also be due to the stimulating
action of CCK and secretin on the pyloric sphincter.
 Regulation of gastric emptying
Gastric factors
• ↑ food volume in stomach promotes ↑ emptying
• Gastrin slightly ↑ activity of pyloric pump
Type of food ingested
• Gastric emptying is slowed maximally by fat, then by
protein, and then by carbohydrates.
Duodenal factors (inhibitory)
• Enterogastric nervous feedback reflexes
• Hormonal feedback
– Cholecystokinin (CCK) – stimulated by fatty substance
in chyme – act as inhibitor of gastrin.
– Secretin & GIP (gastric inhibitory peptide)