Gastrointestinal Physiology

1. Sites of absorption of major nutrients[1]

Stomach

Alcohol, weak acid (eg. Asprin)

Proximal small intestine (duodenum/proximal Jejunum)

Iron, Calcium, Fat, Sugars, Amino Acids

Middle Small Intestine (distal Jejunum/proximal ileum)

Sugars, Amino Acids

Distal Small Intestine (Ileum)

Bile Salts

Vitamin B₁₂

2. Bile production and enterohepatic circulation[2]

- Bile is composed of:

1. Bile salts

a. Bile salts are organic anions synthesized by hepatocytes from cholesterol (this is a major route for cholesterol removal)

i. They become conjugated to amino acids

ii. Bile synthesis is dependent on the presence of 7α-hydroxylase

b. Note: rate of bile synthesis is dependent on the amount of bile acids returned to the liver – only 5% of bile salts is lost in feces

2. Phospholipids

3. Cholesterol – from the blood

4. Bilirubin

a. Heme catabolism in reticuloendothelial system

b. Bilirubin-albumin complex is transported to the liver

c. Bilirubin is excreted w/ bile into Duodenum

5. Water (97%)

- Bile salts are the key component of bile – responsible for micelle formation and the solubilization of lipids for absorption

- Bile salts are then reabosorbed in the terminal ileum and transported back to the liver via the portal system

3. Glucose cotransport into cells of gut[3]

- Glucose is taken up by a membrane transporter (a sodium linked glucose transporter) in the brush border of jejunal enterocytes

1. this transporter uses the Na⁺ concentration gradient (High lumenal, low intracellular) to co-transport glucose

2. GLUT2 transporter is on the basal side of the enterocytes and transports glucose into the blood

4. Fat digestion and absorption[4]

1. emulsification in the stomach (bile acids are not necessary for emulsification) – the breakdown of fat and stabilization by lecithin and proteins

2. In the duodenum, fat is further digested by pancreatic lipase (remember that colipase is needed to anchor lipase to the fat droplets)

a. Cholesterolesterase (nonspecific esterase) cleaves cholesterol

b. Phospholipase A2 digests phospholipids

3. in the Small intestine, fatty acids are solubilized by Bile acids (this is when they are necessary) to form a mixed micelle and are transported to the lumen brush border of jejunum

4. At the brush border there is a low local pH of 6 – this allows for the release of free fatty acids, phospholipids and cholesterol – and they can diffuse across the lipid bilayer

5. in the enterocytes, fatty acids and monoglycerides are resynthesized into triglycerides; phospholipids are resynthesized; and cholesterol is resynthesized in the smooth ER.

6. The newly formed TG’s, phospholipids, and cholesterol are packaged into chylomicrons mixed with lipoproteins.

7. These are transported via the lacteals into the blood stream via the thoracic duct

8. Note: glycerol and middle chain FA’s are small enough to enter capillaries and are transported in the blood.

5. Secretion and actions of GI hormones[5]

a. Cholecystokinin

- Secreted in response to amino acids and fatty acids entering the duodenum

- Secreted by I cells of duodenum and jejunum

- Stimulates contraction of gallbladder

- Causes pancreatic secretion of HCO₃^-

- Inhibits gastrin H⁺ secretion

- Inhibits gastric emptying

b. Gastrin

- Secreted by parietal cells in response to stomach distension, amino acids, peptides, vagus innervation

- Inhibited by secretin and stomach acid pH<1.5

- Stimulated secretion of HCl, intrinsic factor, and pepsinogen

- Stimulates gastric motility

c. Secretin

- Secreted in response to acid and fatty acids entering the duodenum

- Secreted by S cells of duodenum

- Stimulates pancreatic secretion of HCO₃^-

- Inhibits gastrin H⁺ secretion

d. Somatostatin

- Secreted in response to acid, inhibited by vagus

- Secreted by D cells in pancreatic islets, gastrointestinal mucosa

- Inhibits gastric acid and pepsinogen secretion

- Inhibits pancreatic small intestine fluid secretion

- Inhibits gallbladder contraction

- Inhibits release of both insulin and glucagon

e. Vasoactive Intestinal Peptide (VIP)

- Secreted by smooth muscle and nerves of intestines

- Relaxes intestinal smooth muscle

- Causes pancreatic secretion of HCO₃^-

- Inhibits gastrin H⁺ secretion

[1] GI: Integrated Physiology of Digestion lecture from Dr. Williams (scribe: R. Soyomboa, Tuesday 1/9/01 p.5)

[2] First Aid: p. 376, GI: Liver Physiology lecture from Dr. Van Dyke (scribe: D. Ward, Tuesday, 1/16/01 p. 7)

[3] GI: Integrated Physiology of Digestion lecture from Dr. Williams (scribe: R. Soyomboa, Tuesday 1/9/01 p.3)

[4] GI: Integrated Physiology of Digestion lecture from Dr. Williams (scribe: R. Soyomboa, Tuesday 1/9/01 p.4)