1. THE DIGESTIVE SYSTEM 3- Small Intestine to Large Intestine
PHYSIOLOGY-2
PHL226
Dr/ Abdulaziz bin Saeedan Pharmacy College

2. Small Intestine (Bowel)
The small intestine is a long tube (6 m long), SO it fills most of the abdominal cavity.
The small intestine is called small because the diameter or the width of the tube is much less than the large intestine.
The small intestine plays the most important role in the digestion and absorption of nutrients.
The digestive process in the small intestine is completed by bile, pancreatic juice and intestinal juice.
90% of nutrient absorption occurs in the small intestine, and the other 10% occurs in the stomach and large intestine.
The small intestine consists of 3 segments:
1- The duodenum (25 cm long).
2- The jejunum (1.5 m long).
3- The ileum (3.5 m long).
Each segment performs an important role in digestion and/ or absorption.

3. The surface area of the small intestine is increased in three ways.
1- Circular Folds (the plicae circulares):
The intestinal mucosa is not smooth, but arranged into circular folds.
These folds occur from the duodenum to the middle of the ileum.
The circular folds increases the surface area and force the chyme forward in spiral movement causing more contact with the intestinal mucosa SO helps in mixing the chyme with the digestive juice.
2- Villi:
The intestinal mucosa forms finger like projections (1 mm in length) called villi that are covered with the epithelial cells.
The wall of villi is very thin; it is only one cell thick.
The deep cavities between villi are called intestinal crypts (crypts of Lieberkühn).
The intestinal crypts contain the intestinal glands that secretes the intestinal enzymes.

4. 3- Microvilli (brush border):
The epithelial cells which line villi forms little hair-like projections called microvilli which gives brush-like appearance.
The intestinal enzymes are embedded within the plasma membrane of the microvilli SO, they are called brush border enzymes.
NOTE:
The plicae circulares, villi and microvilli increase the surface area SO increase the rate of digestion and absorption.

5. The epithelial cells covering villi are of 2 types:
1- Absorptive epithelial cells (Enterocytes):
Enterocytes synthesize the intestinal digestive enzymes which called brush border enzymes.
They transport the digested nutrient from the lumen of the intestine to the circulatory system.
NOTE:
The chyme must contact the brush border for digestion to occur.
2- Goblet cells:
Goblet cells secrete mucus that protects the epithelial cells against digestion.

6. The process of digestion:
The duodenum is the shortest part of the small intestine (25 cm long) in which most of the digestion of food substances occur.
It receives the chyme from the stomach and digestive secretions from the liver (gallbladder), the pancreas, and from the intestinal glands.
The presence of fatty chyme in the duodenum, stimulates the enteroendocrine cells to release cholecystokinin hormone (CCK) into the bloodstream.
The presence of acid chyme in the duodenum, stimulates the enteroendocrine cells to release secretin hormone and gastric inhibitory peptide (GIP).
NOTE:
Enteroendocrine cells locate in the lower portion of the intestinal crypts.

7. The main functions of cholecystokinin (CCK):
CCK inhibits the gastric motility indirectly; by inhibiting G-cells that produce gastrin.
It stimulates the liver to produce bile.
It stimulates the contraction of gallbladder and relaxes the sphincter of Oddi so, bile releases into the duodenum.
It stimulates the exocrine regions of the pancreas to secret pancreatic enzymes.
The main functions of secretin:
Secretin inhibits both the chief and parietal cells of the stomach.
It stimulates the pancreatic ducts to secrete sodium bicarbonate which neutralizes the acidic chyme in the duodenum.
It stimulates Brunner's glands (found only in the duodenum) to secrete alkaline mucus that neutralizes the acidic chyme in the small intestine.
The main functions of gastric inhibitory peptide (GIP):
GIP has the opposite effects of gastrin.
It inhibits the gastric motility.
It inhibits the gastric acid secretion.
It stimulates the release of insulin in response to infusions of glucose.

8. Digestive juices in the SI:
I. Bile II. Pancreatic secretions III. Intestinal secretions
I.  Bile:
Bile is a digestive juice that is secreted by the liver cells (hepatocytes) and stored in the gallbladder.
The liver secretes 600 – 1000 mL of bile in a day.
It is golden yellow (or greenish) in color due to the presence of bile pigments (bilirubin).
Bile is secreted by the liver continuously, but released into the duodenum only under the stimulation of CCK.
Secretion of bile into the duodenum occurs according to the amount of fat in the food.
Bile composition:
Water.
Bile salts (derivatives of cholic acid as sodium cholate).
Bile pigment (bilirubin).
Phospholipids and cholesterol.
Electrolytes as sodium, potassium, calcium, chlorine and bicarbonate ions.

9. Functions of the bile:
1- Emulsification of lipids (fats):
In the duodenum, the bile salts act to separate the large fat globules into smaller droplets called micelles through a process called emulsification.
Emulsification is the process by which large globules of fats are broken down into smaller droplets called micelles.
Micelles are water soluble droplets so they can mix with water and digested by pancreatic juice.
2- The bile elevates the pH of the duodenal contents, to provide an ideal neutral or slightly alkaline environment for the digestive enzymes in the small intestine.
3- The bile help the absorption of vitamin K from the diet.

10. NOTES:
Bile does not contain digestive enzymes but contain bile salts that have a digestive function.
Bilirubin (bile pigment) is a metabolic breakdown product of hemoglobin that give bile its characteristic greenish color. Bilirubin is further metabolized by bacteria in the colon into stercobilin, which give the feces its characteristic brown color.

11. II.  Pancreatic secretions:
At the same time that bile is released by the gall bladder, pancreatic juices are secreted by the pancreas into the duodenum.
The pancreas is a large gland located below the stomach that secretes pancreatic juice into the duodenum via the pancreatic duct.
The pancreas has 2 main functions :
A- Endocrine functions that regulates blood sugar.
B- Exocrine functions that helps in digestion.
A- Endocrine functions: include hormone secretion
1- Insulin: (50– 80%)
It is a hormone that is produced by beta cells that are locate in the islets of Langerhans of the pancreas.
High blood glucose level stimulates beta cells to release insulin
Insulin decreases blood glucose level by stimulating the cells in the liver and skeletal muscles to take up glucose from the blood.
In the liver and skeletal muscles, glucose is stored as glycogen.

12. 2- Glucagon: (15 – 20%).
It is a hormone that is produced by pancreatic alpha cells.
Low blood glucose level stimulates alpha cells to release glucagon.
Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream, so raises blood glucose level
NOTE:
Effect of glucagon is opposite to that of insulin.
3- Somatostatin: (3– 10%).
It is a hormone that is produced by pancreatic delta cells.
Somatostatin suppresses the release of gastrointestinal hormones (Gastrin, CCK, Secretin, GIP).
It suppresses the release of pancreatic hormones (insulin, glucagon).
It suppresses the exocrine secretory action of pancreas.

13. B- Exocrine functions:
The exocrine functions of the pancreas include secretion of digestive juice called pancreatic juice
CCK and secretin are digestive hormones that stimulates the pancreas to release the pancreatic juice.
Components of the pancreatic juice :
1- Sodium bicarbonate Pancreatic enzymes Zymogens
1- Sodium bicarbonate:
Sodium bicarbonate neutralizes the acidic chyme entering the duodenum and elevates the duodenal pH to about which is the optimum pH for the pancreatic and the intestinal enzymes.
The neutralization is important because the enzymes in the small intestine need a neutral environment or slightly alkaline pH.

14. Fats 𝐿𝑖𝑝𝑎𝑠𝑒 Fatty acids+glycerol
2- Pancreatic enzymes:
a- Pancreatic amylase :
All carbohydrates in the small intestine must be hydrolyzed to monosaccharides prior to absorption.
Amylase enzyme hydrolyzes starch to the disaccharide; maltose.
Carbohydrates OR Starch 𝑝𝑎𝑛𝑐𝑟𝑒𝑎𝑡𝑖𝑐 𝑎𝑚𝑦𝑙𝑎𝑠𝑒 maltose
b- Lipase enzyme:
It helps in the digestion of fats/ lipids into fatty acids and glycerol, which can be easily absorbed by the intestinal surface.
Fats 𝐿𝑖𝑝𝑎𝑠𝑒 Fatty acids+glycerol

15. c- Zymogens: Trypsinogen and Chymotrypsinogen.
Zymogens are digestive enzymes that synthesized inside the exocrine cells of the pancreas and released into the duodenum in inactive forms (so called proenzymes).
If they are synthesized in an active form, they will digest the internal protein structures of the exocrine cells (auto-digestion).
Trypsinogen is secreted from the pancreas in an inactive form, and then activated by the intestinal enzyme enterokinase (enteropeptidase) into trypsin.
Chymotrypsinogen is secreted from the pancreas in an inactive form, and then activated by trypsin into chymotrypsin.
Trypsin and chymotrypsin are proteolytic enzymes (proteases). They are known as endopeptidases. They are responsible for the initial breakdown of polypeptides into short peptide chains (dipeptides).
The dipeptides are then digested to individual amino acids by carboxypeptidase enzyme from the pancreas and aminopeptidase enzyme from the intestinal epithelium.
NOTE:
Trypsin and chymotrypsin are much more powerful than pepsins, so the greater part of protein digestion occurs in the duodenum and upper jejunum.

16. III.  Intestinal secretions:
The intestinal glands in the intestinal crypts secrete 1 to 2 L of intestinal juice per day in response to acid and distension of the intestine.
The intestinal secretions contains:
a- Bicarbonate:
Cells in the duodenum produce large amounts of bicarbonate to completely neutralize any gastric acid that passes down into the digestive tract.
b- Mucus:
Brunner's glands in the duodenum secrete alkaline mucus containing bicarbonate (in response to secretin).
This alkaline mucus in combination with bicarbonate from the pancreas and bile, neutralizes the gastric acid in the incoming chyme.
Goblet cells in the duodenal mucosa also produce mucus.
This mucus lubricates the intestinal contents and protects the duodenal wall against the digestive juices.

17. c- Intestinal enzymes (brush border enzymes):
Enterokinase - activates trypsinogen into trypsin.
Aminopeptidase - hydrolyzes dipeptides into amino acids.
Enzymes that hydrolyzes disaccharides into monosaccharides are:
maltase hydrolyzes maltose into glucose.
sucrase hydrolyzes sucrose (common table sugar) into glucose and fructose.
lactase hydrolyzes lactose (milk sugar) into glucose and galactose.
NOTE:
Lactose becomes indigestible after age 4 in many humans due to decline in lactase production (lactose intolerance).

18. NOTES:
Enzymes released into the duodenum are still active in the jejunum, and can digest carbohydrates, fats and protein.
Digestion of starch starts in the mouth by salivary amylase and completed in the small intestine by pancreatic amylase.
Digestion of protein starts in the stomach by pepsin and ends in the small intestine by trypsin, chymotrypsin, carboxypeptidase and aminopeptidase enzymes.
Digestion of fat starts in the small intestine and ends in the small intestine by lipase enzyme.
All proteolytic enzymes are secreted in an inactive form, to prevent auto-digestion, and are activated in the lumen of the gut:
by HCl in case of the stomach pepsin.
by enterokinase (enteropeptidase) in case of trypsin.
by trypsin in case of chymotrypsin.
Minerals, vitamins, and cholesterol are not broken down and are absorbed unchanged.
Peyer's patches are clusters of lymphatic nodules found in the ileum. They represent a part of the gastrointestinal immune system that destroys the pathogenic microorganisms in the GIT.

19. Absorption
Absorption is the movement of the digested material from the GIT into the bloodstream.
Each villus contains both blood capillaries and a lacteal (lymph vessel) for the absorption of nutrients.
The blood capillaries absorbs glucose, fructose, galactose, amino acids in addition to vitamins, minerals and transport them to the liver via the hepatic portal vein.
The lacteals absorbs the products of fat digestion (fatty acids and glycerol) into the lymphatic system then to the bloodstream.

20. The majority of nutrient absorption occurs in the duodenum and jejunum.
The duodenum absorbs carbohydrates, proteins, and minerals including calcium and iron.
The jejunum absorbs remaining carbohydrates and proteins passed from the duodenum in addition to vitamin C,
vitamin B-2, B-6 and folic acid.
The ileum absorbs vitamine B12, bile salts, fat, cholesterol and fat-soluble vitamins (A, D, E and K).
Vitamin B12 and bile salts are absorbed in the terminal ileum.
Removal of this portion of the ileum will necessitate supplementary vitamin B12 doses for rest of the life (by injection).
Water (90-95% of the daily fluid intake) is absorbed through the small intestine.

21. Function of the small intestine:
1- Digestion:
Carbohydrates into monosaccharides.
Proteins into amino acids.
Fats into fatty acids and glycerol.
2- Absorption of monosaccharides, amino acids, fatty acids, glycerol as well as water, vitamins and electrolytes into the bloodstream.

22. To build the cells and tissues. To provide energy.
In the liver:
The liver processes nutrients by filtering out any harmful substances or wastes before the nutrients can be carried in the blood to the rest of the body.
The processed nutrients are used by different organs:
To build the cells and tissues.
To provide energy.
2. Blood glucose levels are regulated.
Excess glucose is stored in the liver in the form of glycogen in response to the hormone insulin.
When blood glucose level begin to drop, (eg. between meals), the glycogen is re-converted to glucose in response to the hormone glucagon.
At the end of the SI, the non digested chyme (fibers, 3-5% of ingested protein and water) passes through the ileocecal valve to the large intestine.
Ileocecal valve is a sphincter that controls the flow of materials from the ileum into the cecum of the large intestine and prevent back flow of fecal contents from the large intestine into small intestine.

23. The large intestine (Colon)
The large intestine is a muscular tube that connects the small intestine to the rectum.
It forms the last section of the digestive tract, which is about 1.5 m long.
The large intestine performs the vital function of converting food into feces.
There is no secretion of digestive enzymes and any digestion that takes place in the colon is carried out by microbes.

24. The LI is composed of 4 segments:
1- Cecum Colon
3- Rectum Anal canal (ends with anus).
The appendix is a small tube attached to the cecum.
The appendix contain a lymphoid tissue that is filled with lymphocytes, but its removal has no any negative effect on the immune system.
The cecum leads to the colon before entering the rectum.
The colon is consists of 4 sections:
1- Ascending colon (right).
2- Transverse colon.
3- Descending colon (left).
4- Sigmoid colon.
The colon is the major reservoir for intestinal bacteria.

25. There are trillions of microbial population in the LI called the microflora.
Importance of microflora:
1- Digestion of substances in the chyme that are not digestible by the SI (bacterial fermentation).
NOTE:
Gases such as CO2 and methane are produced as a byproduct of bacterial fermentation that lead to flatulence (passing of gases through the anus).
2- Synthesis of some vitamins:
a- Vitamin K:
It is a fat-soluble vitamin that the liver needs in order to synthesize 4 clotting factors, including prothrombin.
Intestinal bacteria produces about half of our daily vitamin K requirements.

26. b- Vitamin B12:
It is a water-soluble vitamin that is necessary for the normal function of nerve cells in the body and for the formation of red blood cells.
c- Biotin:
It is a water-soluble vitamin that is important to various reactions, especially those of glucose metabolism.

27. Functions of the LI:
1- Little absorption occurs in the large intestine
it absorbs most of the remaining water. The colon absorbs on average 1–1.5 liters of fluid every day.
it absorbs electrolytes, particularly sodium and potassium.
it absorbs vitamins produced by bacteria.
2- Bacterial digestion:
The large population of bacteria digest fiber content of the chyme through the process of fermentation to produce short chain fatty acids.
3- Storage of fecal material (stool) until defecation .
NOTES:
The stool itself is mostly food debris and bacteria.
Normal stool weight is approximately 250 g daily, of which 10 to 20% is bacteria. It contains indigestible fiber, water, electrolytes, and small amounts of protein and fat.
Q- What occurs when too much water is removed from stools in the large intestine?
A. Constipation