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3. 
3.2.3.5. GIT Splanchnic circulation - regulation mostly metabolic
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Gastrin
[WG21:p489]
Produced by G cells in the lateral walls of the glands in antral portion of stomach
4 forms: G34, G17, G14, and carboxyl terminal tetrapeptide
G17 is the main one. T1/2=2-3min
Actions
Stimulation of
- Gastric acid secretion
- Pepsin secretion
- Mucosa growth in stomach, and small and large intestines
- Gastric motility
- Insulin secretion (only after a protein meal, not a carbohydrate meal)
- Glucagon secretion
Regulation
Stimulated by
- Gastrin-releasing polypeptide
* Not by Ach - Presence of penylalanine and tryptophan
Inhibited by
- Acid in antrum
* By direct action on G cells and by release of somatostatin
Cholecystokinin (CCK)
Aka cholecystokinin-pancreozymin (CCK-PZ)
Secreted by endocrine cells (I cells) in the upper intestine
Also found in other places e.g. nerves, brain
T1/2 = 5 min
Action
- Contraction of the gallbladder
- Secretion of pancreatic juice rich in ENZYMES
- Augments action of secretin (which causes secretion rich in HCO3)
- Inhibis gastric emptying
- Trophic effect on pancreas
- Increases secretion of enterokinase
- May enhance motility of small bowel and large bowel
- Contraction of pyloric sphincter
* Along with secretion - Stimulate glucagon secretion
* With gastrin
Regulation
Increased by
- Contact of intestinal mucosa with products of digestion
* Esp peptides and amino acids, fatty acids (more than 10 carbon)
NB:
- Positive feedback situation
--> Stimulation release of bile and pancreatic juice
--> Bile and pancreatic juice break down fat and protein
--> These products stimulates further CCK
Secretin
Secreted by S cells deep in the glands of the mucosa of the upper portion of small intestine
T1/2 = 5 min
Actions
- Increases secretion of bicarbonate by duct cells of the pancreas and biliary tract
--> Causes watery, alkaline pancreatic juice
* via cAMP - Decreases gastric acid secretion
- May cause contraction of pyloric sphincter
Gastric inhibitory polypeptide (GIP)
Produced by K cells in mucosa in duodenum and jejunum.
Action
- In large doses, inhibits gastric secretion and motility
--> But not in physiological level - May stimulate insulin secretion at physiological level
Regulation
- Stimulated by glucose and fat in duodenum
VIP
Markedly stimulates intestinal secretion of electrolyte and water
Relaxation of intestinal smooth muscle
Dilation of peripheral blood vessels
Inhibition of gastric acid secretion
Potentiates action of acetylcholine in salivary gland
Motilin
Secreted by enterochromaffin cells and Mo cells in the stomach and bowels
Acton
Contraction of smooth muscle in the stomach and intestine
Major regulator of MMC (migrating motor complexes)
Somatostatin
Inhibits secretion of gastrin, VIP, GIP, secretin, and motilin
Secretion stimulated by acid in stomach
Saliva
Contains
Lingual lipase
Salivary alpha-amylase
Mucin
IgA
Lactoferrin
Proline-rich protein
Function
Facilitates swallowing
Keep mouth moist
Solvent for taste
Aid speech
Keep mouth and teeth clean
Some antibacterial action
Stimulated by parasympathetic nerve
Swollow involves afferent impulse in trigeminal, glossopharyngeal, and vagus nerve
Effecterent to pharyngeal musculature and tongue via trigeminal, facial and hypoglossal
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3 components of lower oesophageal sphincter
[WG21:p494]
Oesophageal smooth muscle
* i.e. intrinsic sphincter
Fibres of the crural portion of the diaphragm
* i.e. extrinsic sphincter
Oblique or sling fibres of the stomach wall
* Creating a flap valve
Tone of LES is under neural control
Release of Ach from vagal endings
--> Intrinsic sphincter to contract
Release of NO and VIP from interneurons innervated by other vagal fibres
--> Relax of LES
Extrinsic sphincter is innervated by the phrenic nerve
--> Coordination with respiration and contractions of chest and abdo muscles
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[WG21:p501]
Pancreatic juice
1500mL of pancreatic juice secreted per day
Contains
- Trypinogen
* Converted to trypsin by brush border enzyme enteropeptidase (enterokinase) - Trypsin inhibitor
- HCO3
- Chymotrypsinogen
- Proelastase
- Procarboxypeptidase
- Pancreatic lipase
- Pancreatic alpha-amylase
- Phospholipase A2
Trypsin converts chymotrypsinogen into chymotrypsin and also activate trypsinogen
Regulation
- Secretin
--> Increase HCO3 content and volume
(acting on pancreatic ducts) - CCK
--> Increase enzyme content but low in volume
(acting on acinar cells) - Ach
--> Also increase enzyme content
(acting on acinar cells via phospholipase C)
NB: In small ducts, HCO3 is secreted
In larger ducts, HCO3 is reabsorbed in exchange for Cl-
[WG21:p502]
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[WG21:p504]
Blood flow from portal space (with bile duct, portal vein, and hepatic artery)
--> Towards central vein
Functions of liver
- Formation and secretion of bile
- Metabolism and vitamin metabolism
- Inactivation of substances
- Synthesis of plasma protein
- Immunity
Bile salt
2 principle bile salts are cholic acid and chenodeoxycholic acid
In colon, bacterial conversion:
Cholic acid --> deoxycholic acid
Chenodeoxycholic acid --> lithocholic acid
Percentage in bile:
- Cholic acid = 50%
- Chenodeoxycholic acid = 30%
- Deoxycholic acid = 15%
- Lithocholic acid = 5%
Function
Reduce surface tension
Emulsification of fat (in conjunction with phospholipids, monoglycerides)
--> Forming micelles
Micelles are only formed when bile salt reach a certain level
- 95% of bile salts are absorbed from small intestines
- Most are absorbed from terminal ileum
* By Na-bile salt symporter
* Powered by basolateral Na-K ATPase
Remaining bile salts enter the colon and are converted to salts of deoxycholic acid and lithocholic acid
Lithocholic acids are relatively insoluble and is mostly excreted in stools
* Only 1% resorbed
Total bile pool =3.5g
Rate of synthesis = 0.2-0.4g/day
Bile recycles about twice per meal and 6-8 times per day
Regulation
Cholagogues (Gallbladder contraction)
- CCK
* Triggered by presence of fatty acids and amino acid in duodenum
Choleretics (Increase in secretion)
- Stimulation of vagus nerve
- Secretin
- Bile salt