Functions of the GI Tract

Ingestion: Taking in food

Digestion: Chemical and Mechanical

Absorption: moving nutrients from the lumen of the GI tract into the cells of the body

Excretion: getting rid of undigested and unabsorbed material

Movement: movement of ingested food throughout the GI tract

Organs of the Digestive System

Accessory Digestive Organs:

– Salivary glands

– Liver, gall bladder

– Pancreas

Digestive Tract:

– Oral Cavity

– Pharynx

– Esophagus

– Stomach

– Small Intestine

– Large Intestine

Histology of the Stomach• Cell types:

Chief cells: produce pepsinogen (inactive precursor to pepsin)

Parietal cells: produce HCl and intrinsic factor (absorption of vitamin B12; important in RBC maturation)

“Endocrine” cells:

• G cells: gastrin

• D cells: somatostatin (paracrine)

• Enterochromaffin-like cells: histamine (paracrine)

The gastrointestinal hormones (or gut hormones) constitute a group of hormones secreted by

enteroendocrine cells in the stomach, pancreas, and small intestine that control various

functions of the digestive organs.

Enteroendocrine cells do not form endocrine glands but are spread throughout the digestive

tract. They exert their autocrine and paracrine actions that integrate all of gastrointestinal

function.

GI Hormone

Regulation of GI function

Endocrine regulation : Enteroendocrine cells (EEC) secretes regulatory peptide or hormones

that travel via blood stream to remote target organ. Ex. gastrin, secretin

Paracrine regulation : Regulatory peptide secreted by EEC acts on a nearby target cell by

diffusion through interstitial space. Ex. histamine, 5-HT

Classification of GI hormones

The gastrointestinal hormones can be divided into the following groups based upon their

chemical structure.

Gastrin-cholecystokinin family: gastrin and cholecystokinin

Secretin family: secretin, glucagon, vasoactive intestinal peptide (VIP) and gastric inhibitory

peptide (GIP)

Somatostatin family

Motilin family

Substance P

GI Hormone Gastrin

Gastrin is a peptide hormone that stimulates secretion of

gastric acid (HCl) by the parietal cells of the stomach and

aids in gastric motility.

It is released by G cells in the antrum of the stomach,

duodenum, and the pancreas.

It binds to cholecystokinin B receptors to stimulate the

release of histamines in enterochromaffin-like cells.

It induces the insertion of K+/H+ ATPase pumps into the

apical membrane of parietal cells (which in turn increases

H+ release).

Release is inhibited by highly acidic pH (< 2.0).

Regulation of gastrin secretion

↑ gastrin secretion

Luminal : peptide, amino acids (Phy, Tryp), gastric distention

Neural : vagal stimulation via GRP (can’t be blocked by atropine)

Blood : Ca, epinephrine

↓ gastrin secretion

Luminal : acid, somatostatin

Blood : secretin, GIP, VIP, glucagon, calcitonin

Gastrin secretion and regulation

Feedback inhibition of gastrin

Acid in antrum inhibit gastrin secretion by two ways

1. Direct action on G cell

2. Stimulate release of somatostatin by D cell

In condition which parietal cells are damaged, pernicious anemia, gastrin level is elevated.

Gastrin is produced at excessive levels.

Often by a gastrinoma (gastrin-producing tumor, mostly benign)

of the duodenum or the pancreas.

In autoimmune gastritis, the immune system attacks the

parietal cells leading to hypochlorhydria (low stomach

acidity).

This results in an elevated gastrin level in an attempt to

compensate for increased pH in the stomach

Eventually, all the parietal cells are lost and achlorhydria

results leading to a loss of negative feedback on gastrin

secretion.

How it occurs:

Zollinger-Ellison syndrome

Cholecystokinin-Pancreozymin (CCK)

Cholecystokinin (CCK or CCK-PZ) is a peptide hormone of the gastrointestinal system

responsible for stimulating the digestion of fat and protein.

Cholecystokinin (pancreozymin) is synthesized by I-cells in the mucosal epithelium of

the small intestine.

Secreted in the duodenum, the first segment of the small intestine.

Causes the release of digestive enzymes and bile from the pancreas and gallbladder.

CCK secretion

Cholecystokinin-Pancreozymin (CCK)

CCK is composed of varying numbers of amino acids depending on post-translational modification

of the CCK gene product, preprocholecystokinin.

CCK8, CCK22, CCK33 : principal circulating forms secreted in response to meal.

Every forms has the same 5 aa at C-terminal as gastrin

Action of CCK

Gall bladder contraction, sphincter of Oddi

relaxation

↑ pancreatic enzyme secretion

Augment effect of secretin in producing

alkaline pancreatic juice

↓ gastric emptying

Induced satiety by acting through hypothalamus

Mechanism of action

Through CCK receptor (2 type)

1. CCK-A : Primarily gastrointestinal tract, lesser

amounts in the CNS

2. CCK-B : Primarily CNS, lesser amounts in the

gastrointestinal tract

CCK bind to receptor activate phospholipase

C → IP3, DAG → ↑ intracellular Ca → activate

protein kinase → release of granule

(pancreatic enzyme)

Mechanism of action Pancreatic cell type

Control of CCK secretion

Most potent stimulator of CCK release is lipid

Peptones, amino acid also increase CCK release.

Also secreted in response to CCK-releasing factor

Positive feedback : CCK → enzyme release → more digestive products → more CCK (stop when

digestive products move to next part)

CCK-releasing peptide & monitor peptide

CCK-RP is secreted from duodenal mucosa, andmonitor peptide by pancreatic acinar cell

Secreted in response to fat, protein digestive products,and also to neural input (cephalic phase)

These peptides are degraded by pancreatic trypsin (ifthere are proteins in duodenum, these peptides won’tbe degraded and CCK will be released )

Secretin 27 amino-acid polypeptide

Secreted by S cell located deeply in the mucosal gland of duodenum and jejunum

Similar structure with glucagon, VIP, GIP

Only 1 form has been isolated

t1/2 : 5 min

Stored in an inactive form (prosecretin)

Action of secretin

Most potent humoral stimulator of fluid and HCO3 secretion by pancrease

Acts in concert with CCK, Ach to stimulate HCO3 secretion

↑ HCO3 secretion by duct cells of pancrease and biliary tract→ ↑secretion of a watery,

alkaline pancreatic juice

Acting through cAMP

↑ pancreatic enzyme secretion (augment CCK)

↓ gastric acid secretion

Pyloric sphincter contraction

Stimulate growth of exocrine pancrease (work with CCK)

Action of secretin

Mechanism of action

Action of secretin & CCK in pancrease Control of secretin secretion

Secretin is secreted in response to protein digestive products, bile acid, fatty food and increased acidity in duodenal content (pH< 4.5-5)

Inhibited by somatostatin and Met-enkephalin

Secretin release may be mediated by secretin-releasing peptide

Gastric inhibitory polypeptide (GIP)

GIP is a member of the secretin family of hormones.

It is derived from a 153-amino acid proprotein encoded by the GIP gene and circulates as

a biologically active 42-amino acid peptide.

It is synthesized by K cells, which are found in the mucosa of the duodenum and the

jejunum of the gastrointestinal tract.

Like all endocrine hormones, it is transported by blood.

GIP receptors are seven-transmembrane proteins found on beta-cells in the pancreas.

Action of GIP

Stimulated by glucose and fat in duodenum, acid in stomach

Mild effect in decreasing gastric motility

Inhibit gastric acid secretion by directly inhibit parietal cells or indirectly inhibit gastrin

release from antral G cells (via somatostatin)

Stimulate insulin release from pancreatic islet in response to duodenal glucose and fatty acid

For this action, it has also been referred to as glucose-dependent

insulinotropic peptide.

Vasoactive intestinal peptide (VIP)

28 amino-acid polypeptide

Released in response to esophageal

and gastric distention, vagal

stimulation, fatty acid and ethanol in

duodenum

Amino acid and glucose don’t affect

VIP release

Half life 2 min in circulation

Action of VIP

VIP seems to induce smooth muscle relaxation

(stomach, gallbladder), stimulate secretion of

water into pancreatic juice and bile, and cause

inhibition of gastric acid secretion and

absorption from the intestinal lumen.

It also has the function of stimulating

pepsinogen secretion by chief cells.

VIP a crucial component of the mammalian

circadian timekeeping machinery.

It is also found in the heart and has significant

effects on the cardiovascular system. It causes

coronary vasodilation.

Somatostatin

Growth hormone inhibitory hormone (GH-IH)

First found in hypothalamus

Secreted by D cell in stomach, duodenum,

pancreatic islet

Secreted in larger amount into gastric lumen

> circulation

Released in response to acid in stomach

Presented in 2 forms

1.Somatostatin 14 : prominent in hypothalamus

2.Somatostatin 28 : prominent in GI tract

Acts through G-protein couple receptor (inhibit adenylate cyclase)

Somatostatin

Action of somatostatin

Inhibit secretion of gastrin, VIP, GIP, secretin, motilin, GH, insulin, glucagon

↑ fluid absorption and ↓ secretion from intestine

↓ endocrine and exocrine pancreatic secretion

↓ bile flow and gall bladder contraction

↓ gastric acid secretion and motility

↓ absorption of glucose, amino acid, triglyceride