03 September 2016

Lecture #8: THE GASTROINTESTINAL TRACT: ANATOMY & PHYSIOLOGY



Digestion is the process of reducing food to smaller molecules that can be absorbed in the body. Three organs play an important role in the digestion process. These are the gastrointestinal tract, the liver and the pancreas.

The organs that compose the GIT are the:

1.      Mouth
2.      Pharynx
3.      Esophagus
4.      Stomach
5.      Small intestine
6.      Large intestine

THE STOMACH

Structure

1.      The size of the stomach varies according to factors such as gender and amount of distention.

2.      When no food is in the stomach, it is about the size of a large sausage.

a.      In adults, capacity ranges from 1.0 to 1.5 L.

3.      Stomach location: upper part of the abdominal cavity under the liver and diaphragm.

4.      Divisions of the stomach

a.      Fundus – enlarged portion to the left and above the opening of the esophagus into the stomach.

b.      Body – central portion of the stomach.

c.       Pylorus – lower part of the stomach.

5.      Curves of the stomach

a.      Lesser curvature – upper right curve of the stomach.
b.      Greater curvature – lower left curve of the stomach.

6.      Sphincter muscles – circular fibers arranged so that there is an opening in the center when relaxed and no opening when contracted

The Stomach Wall

1.      Gastric mucosa

a.      Epithelial lining has rugae marked by gastric pits

b.      Gastric glands – found below level of the pits which secrete most of the gastric juice.

c.       Chief cells – secretory cells found in the gastric glands and secrete the enzymes of the gastric juice.

d.     Parietal cells – secretory cells found in the gastric gland which secrete hydrochloric acid and thought to produce intrinsic factors needed for Vitamin B12 absorption.

2.      Gastric muscularis – thick layer of muscle with three distinct sublayers of smooth muscle tissue arranged in a crisscrossing patter. This pattern allows the stomach to contrast strongly at many angles.


Functions of the stomach

1.      Reservoir for food until it is partially digested and moved further along the GI tract
2.      Secretes gastric juice to aid in digestion of food.
3.      Breaks food into small particles and mixes them with gastric juice.
4.      Secretes intrinsic factor
5.      Limited absorption
6.      Produces gastrin
7.      Helps protect body from pathogenic bacteria swallowed with food.


Major constituents secreted by the stomach

1.      Hydrochloric acid

2.      Mucus

a.      Major function is to protect the mucosal epithelium from mechanical damage during the passage of food.

b.      Provides a lubricant for the passage of food and its strongly adhesive properties ensure that much of the mucus remains stuck to the mucosa.

c.       It does not provide and impenetrable barrier to acid since it is permeable to H+.

3.      Electrolytes

a.      In the basal states, the major electrolytes in gastric juice are Na+ and Cl with small amounts of H+ and K+.

b.      As the rate of secretion increases, there is a marked increase in H+ concentration and small increases in Cl and K+ concentrations. The sodium concentration decreases.

c.       At all rates of secretion, H+, K+ and Cl concentration are greater than those in serum, whereas, Na+ is lower than that found in serum.

4.      Enzymes

a.      Pepsinogen – secreted by the gastric mucosa as a zymogen and converted to proteolytically active pepsis by the acid pH of the stomach.

(1)   Pepsin aids in the digestion of protein by splitting peptide bonds, especially those involving aromatic amino acids such as phenylalanine, tyrosine and leucine.

(2)   The activity of pepsin is terminated when the acid gastric contents are mixed with alkaline pancreatic secretions in the small intestine.

b.      Gastric lipase – has a broad pH optimum of 4.0 to 7.0 and is stable at pH 2.0. It is important in the digestion of short–chain triglycerides in milk.

5.      Hormones

a.      Gastrin – produced and stored within the G cells located in the antral mucosa, however, is release is inhibited by an acid pH (usually 2.0).

b.      Biologically active forms of gastrin:

(1)   Big gastrin or G34 – twice as abundant as “little gastrin” in blood sample, eventhough it only accounts for 10% of the gastrin contained within the G cells. The reason for this difference is that big gastrin has a half–life of 42 minutes while little gastrin only has 7 minutes. 

(2)   Little gastrin or G17 – results from the cleavage of G34

(3)   Minigastrin or G14

Physiologic effects of gastrin

a.      Gastrin stimulation

(1)   Acid secretion by parietal cell
(2)   Pepsinogen secretion
(3)   Gastric blood flow
(4)   Contraction of the circular muscle of the stomach
(5)   Growth of gastric and small intestinal mucosa and pancreas

b.     Gastrin inhibition

(1)   Contraction of the pyloric sphincter, ileocecal sphincter and sphincter of the hepatopancreatic ampulla.
(2)   Gastric emptying
(3)   Absorption of glucose and electrolytes in the small intestine

c.       Gastrin release

(1)   Insulin
(2)   Glucagon
(3)   Calcitonin

Stimulants for gastrin release

(1)   Major stimulants

Phenylalanine, cysteine, tryptophan, hydroxyproline, tyrosine

(2)   Minor stimulants

(a)   Calcium, beer, wine, coffee
(b)   Vagal stimulation by electric current
(c)    Insulin hypoglycemia
(d)  Injection of 2–deoxyglucose

Concentration

            Fasting = 21 – 105 pg/ml
            Postprandial = increase to 42 – 84 pg/ml (20 – 40 pmol/L)


THE SMALL INTESTINE

Structure

1.      The tube is approximately 2.5 cm in diameter and 6 m in length; coiled loops fill most of the abdominal cavity.

2.      It has the following divisions:

a.      Duodenum – uppermost division; approximately 25 cm long, shaped roughly like the letter C.

b.      Jejenum – approximately 2.5 m long.

c.       Ileum – approximately 3. 5 m long.

3.      Wall of the small intestine:

a.      Intestinal lining has plicae with villi.

b.      Villi – important modification of the mucosal layer.

(1)   Each villus contains an arteriole, venule and lacteal
(2)   Covered by a brush border made up of 1,700 ultrafine microvilli per cell.
(3)   Villi and microvilli increase the surface area of the small intestine hundreds of time.

Function

1.      Completion of digestion of food.

2.      Selective absorption of nutrients and water.

3.      Passage of unabsorbed foodstuff along the digestive tract.

The process of absorption

1.      Absorption is the passage of substance through the intestinal mucosa into the blood or lymph.

2.      Mechanism of absorption

a.      Secondary active transport (e.g. Na+)
b.      Sodium cotransport (coupled transport) – e.g. glucose
c.       Fatty acids, monoglycerides, cholesterol are transported with the aid of bile salts from lumen to absorbing cells of villi.

3.      After food is absorbed, it travels to the liver via the portal system.


Major constituents absorbed by the small intestine

1.      Water and electrolytes

a.      The average daily volume of fluid secreted in the small intestine is approximately 12L. If this volume was not absorbed, death from dehydration would result within 24 hours.

b.      Actively transported ions include Na+, Cl, Fe2+, Ca2+, HCO3

c.       Passively transported ions include Li+, K+, Br, I

d.     Urea and other non–electrolyte are absorbed by means of solvent drag, a movement of solute in conjunction with water flow.

2.      Calcium, magnesium and phosphate

3.      Vitamins

a.      Lipid–soluble vitamins are absorbed after being solubilized with lipid micelles. Once absorbed, these vitamins are incorporated into chylomicrons and transported via the blood.

b.      Water–soluble vitamins are absorbed via passive diffusion except for Vitamin B12, folic acid, thiamine and ascorbic acid.


Major constituents secreted by the small intestine

1.      Enzymes

a.      Salivary and pancreatic alpha amylase
b.      Amylopectin and glycogen
c.       Alpha–limit dextrin
d.     Lactase
e.      Isomaltase
f.        Sucrose and glucoamylase
g.      Enterokinase
h.      Trypsin

2.      Hormones

a.      Cholecystokinin (CCK)

Functions of CCK

(1)   Regulation of gallbladder contraction and gastric emptying
(2)   Neurotransmitter
(3)   Induces satiety signals
(4)   Pancreatic enzyme secretion
(5)   Relaxation of sphincter of Oddi via an indirect neural mechanism.

Stimulants of CCK release

(1)   L–tryptophan, phenylalanine, lysine
(2)   Increase serum calcium level
(3)   Pancreatic juice
(4)   Partially digested fats and proteins

Inhibitors of CCK release

(1)   Somatostatin
(2)   Bile acids

b.     Secretin

Function

(1)   Stimulation of pancreatic bicarbonate and water secretion

(2)   Use clinically in evaluating pancreatic function

Stimulants for secretin release

(1)   Duodenal acidification, below pH 4.0, release of secretion is maximal and is proportional to the amount of acid entering the duodenum.

(2)   Presence of fatty acids

c.       Gastric inhibitory peptide (GIP)

(1)   Inhibition of gastric acid secretion

(2)   Stimuli in insulin release from beta cells of the pancreas and are primarily responsible for the rapid metabolism of an oral glucose load. It has been thus renamed glucose –dependent–insulinotropic peptide.

(3)   Secretion of fluid and electrolyte by the ileal mucosa

d.     Vasoactive intestinal polypeptide (VIP)

Functions of VIP

(1)   Stimulates pancreatic secretion

(2)   Relaxation of lower esophageal sphincter, gastric fundus and anal sphincter

(3)   Gut blood flow and penile erection

(4)   Inhibits pentagastrin and histamine–stimulated gastric acid and pepsin secretion

(5)   Stimulates lipolysis, glycogenolysis and secretion by the small intestine and pancreas

(6)   Neurotransmitter

Stimulants of VIP release

(1)   G proteins
(2)   Activation of adenyl cyclase


MISCELLANEOUS HORMONES OF GI ETIOLOGY

1.      Somatostatin

a.      Functions

(1)   Inhibits release and action of gastrin, CCK, secretin, VIP, motilin, GIP, insulin, glucagon.

(2)   Inhibits gut secretion, gastric acid, pancreatic enzymes, bicarbonate, intestinal fluid and electrolytes.

(3)   At lower doses, it initiates migratory motor complex and increases the rate of gastric emptying

(4)   At higher doses, it inhibits gut motility and gallbladder contraction

(5)   Antitrophic effects in normal tissues.

b.     Stimulants for release

(1)   Ingestion of meal

c.       Inhibitor for release

(1)   Cholinergic stimulation
(2)   Antral acidification

2.      Gastrin–releasing polypeptide

a.      Function

(1)   Stimulates gastrin release from antral G cells.

(2)   Stimulates smooth muscle contraction in the gallbladder, duodenum and stomach

(3)   In brain, has a role in thermoregulation and pain perception

3.      Calcitonin gene–related peptide

a.      Function

(1)   Sensory neurotransmitter

(2)   Inhibits gastric and pancreatic secretion

(3)   Inhibits smooth muscle contraction

(4)   Stimulates somatostatin and acetylcholine release

(5)   Increases mucosal blood flow

(6)   Gastric mucosal cytopectin

4.      Galanin

a.      Function

(1)   Inhibition of postprandial release of neurohumoral substances such as insulin, neurotensin, somatostatin and pancreatic polypeptide.

(2)   Inhibits intestinal motility

5.      Substance P

a.      Functions

(1)   Neurotransmitter substance in small diameter, unmyelinated sensory C fibers and in motor neurons of the myenteric plexus
(2)   Smooth muscle contraction
(3)   Epithelial secretion
(4)   Vasodilation

6.      Enkephalins

a.      Function

(1)   Inhibits gut motility and mucosal secretion
(2)   Stimulates sphincter tone
(3)   Inhibits acetylcholine release from myenteric plexus neurons.

7.      Neurotensin

a.      Function

(1)   Stimulates pancreatic and bicarbonate secretion
(2)   Stimulates colonic motility
(3)   Trophic effects on gastric, small bowel and colonic mucosa
(4)   Binds to mast cells thus releases histamine

8.      Motilin

a.      Functions

(1)   Induction of myoelectric complexes in the antroduodenal region which propagate distally.
(2)   Contraction of duodenal ileal, colonic and gallbladder smooth muscle.
(3)   Gallbladder emptying
(4)   Stimulates pepsis, pancreatic and chloride secretion

9.      Pancreatic polypeptide family

a.      Function

(1)   Inhibits pancreatic bicarbonate and protein secretion
(2)   Relaxation of gallbladder
(3)   Inhibits cholinergic neurotransmitter and activation of inhibitory G proteins.

(4)   Vasoconstrictor 







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