These notes are intended to accompany lectures in Human Physiology by Dr. Peter King at Francis Marion University, Florence, SC 29501.

No vertebrate animals can absorb food directly into their bodies.
Even if liquified to avoid the necessity for physical breakup, the molecules of proteins, lipids and carbohydrates are too big to transport across cell membranes in the digestive tract.

Digestion is the process of breaking down organic molecules into pieces small enough to cross the cell membranes of the digestive tract.
The process of absorption allows the membranes to be crossed and "pieces" to enter the blood.
Eventually they are delivered to cells where they can be used.

Digestion takes place in the digestive tract or gastrointestinal tract, starting at the mouth and ending at the anus, including the esophagus, stomach, duodenum, jejunum, ileum, ascending, transverse and descending colons and the rectum.
Organs closely associated with the GI tract are the liver and the pancreas.

Most of our food falls into the three major groups of organic molecules, namely...
Proteins
Carbohydrates
Lipids

These three food groups are polymers or and can be broken down by enzymes into smaller subunits by a hydrolysis reaction.

Enzymes are biological catalysts.

Enzymes facilitate a chemical reaction without being directly involved.
i.e. AB + enzyme -> A + B + enzyme

Enzymes often end in -ase and are descriptive of the molecules they act on.
i.e. protease, lipase, endopeptidase, carboxypeptidase, amylase.

Many proteases are stored in the body in inactive forms called zymogens.

Proteins
Proteins are made up of amino acid monomers (20 possible) joined together by peptide bonds.
Primary structue - list of AAs
Secondary structure - planes or helices
Tertiary - three dimensional shape
Quaternary - more than one chain

Protein Digestion
Proteases cleave peptide bonds i.e. they breakdown the primary structure.
Exopeptidases cleave the first or last peptide bond.
Endopeptidases cleave internal peptide bonds.
Proteases attract amino acids to an active site in the enzyme and cleave (break) a peptide bond associated with the amino acid.

Different proteases have unique active sites that can attract specific amino acids and only peptide bonds associated with those amino acids will be cleaved.

For example trypsin, secreted by the pancreas, cleaves bonds after lysine and arginine.

Anabolism
Individual amino acids, plus some dipeptides and tripeptides are absorbed by the endothelial cells of the intestine.
Dipeptides and Tripeptides are broken down in these cells and only individual amino acids are absorbed into the blood and distributed around the body.
They are recombined in cells according to RNA templates to form new proteins.

Amino acids may be broken down further in times of energy crisis.
Some amino acids can be synthesized in the body of vertebrates (non essential amino acids).
Others must be ingested (essential amino acids).
Adults must ingest 8 essential amino acids and young children 9.

Carbohydrate digestion
Carbohydrates are complex sugars made up of monomers of monosaccharides.
Generally only monosaccharides are absorbed.
Animals and plants use glucose as an energy currency within the organism.
Plants store this as amylose and animals, including humans, store it as glycogen.

Amylases secreted in the saliva and from the pancreas break up starch and glycogen into smaller oligosaccharides, maltose, maltriose.
Many specific enzymes such as sucrase, lactase, maltase are attached to the intestinal brush border. These enzymes facilitate the breakdown to monosaccharides which will allow absorption.

Lactose is the disaccharide in milk, broken down by the enzyme lactase.
Suckling of young is a characteristic of mammals and all young mammals have the enzyme lactase to allow digestion of lactose. Most mammals do not drink milk after they are weaned.
We have not evolved to have a high milk diet as adults and after the age of 4, lactase becomes less active.
Some adults (possibly up to 50% worldwide) have minimal lactase activity leading to lactose intolerance (see page 662).

Lipid digestion
Most fats ingested are triglycerides i.e. three fatty acid chains connected to a glycerol molecule.
Most lipid digestion takes place in the small intestine, but some gastric lipase is sectreted in the stomach and some lingual lipase is secreted in saliva and remains active in the low pH of the stomach. The most functionally important lipase is pancreatic lipase.
Lipases cleave two of the fatty acid chains from the triglyceride producing free fatty acids and monoglycerides which are absorbed in the intestine.

Problem: How is a non soluble fat digested by enzyme?
Lipases in the mouth and stomach are not very effective because they do not mix well with the lipids. Bile from the liver (via the gall bladder) emulsifies the lipids and increases surface area for action by lipases in the small intestine.

Monoglycerides and fatty acids combine with bile salts and lecithin to form micelles in the intestinal lumen.

Micelles are small and remain suspended in water.

Micelles are transported across the brush border into the cells of the intestinal epithelium, i.e. lipids are absorbed.

Triglycerides are reformed in the epithelium cells of the intestine, combined with cholesterol, phospholipids and proteins to form soluble chylomicrons. Chylomicrons are transported across the basolateral membrane into the interstitial fluid.
Chylomicrons are too big to enter capillaries and are absorbed by lymph vessels (lacteals).

Lets follow the food trail.
Mouth -
Saliva contains amylase and lingual lipase, that begins the breakdown of carbohydrates and lipids.
Chewing (mastication) physically breaks apart the food to allow faster enzymatic digestion

Food moves from mouth to stomach via the esophagus, a muscular tube that moves food by peristalsis.
Can you stand on your head and drink water? ______
How does a giraffe drink from a pond? _______
The epiglottis closes the entrance to the larynx to prevent food entering the lungs.


Stomach
Secretion of pepsinogen from chief cells in stomach lining and hydrochloric acid from parietal cells. Some gastric lipase is also secreted.
HCl causes pH to fall to as low as 2.
Amylase inactivated and pepsinogen activated by low pH. Lingual lipase still active.
Mucus with bicarbonate buffer (from parietal cells) protects stomach lining.

Food is mixed with fluid secreted by the stomach lining to produce chyme.
The mixture of enzymes, water and other exocrine secretions make up the acidic gastric juice (about 2 liters/day).
Circular, longitudinal and oblique muscles distort and distent the stomach in regular waves of contraction to mix the chyme.
Cardiac sphincter prevents chyme going back up the esophagus (acid reflux).

Some protein digestion takes place in stomach to form smaller polypeptides.
Small amount of lipid digestion takes place.
Very little absorption happens in the stomach.
Low pH kills most microorganisms ingested with food.

Small Intestine
Chyme is squirted into the duodenum in small amounts through the pyloric sphincter.

The small intestine is the site of continuing digestion and most nutrient absorption.
It is comprised of the duodenum, jejunum and ileum.
Surface area is increased by many villi and microvilli to facilitate absorption.
Circular and longitudinal muscle control movement of chyme through peristalsis.

Intestinal smooth muscle actually undergoes spontaneous contractions in a similar way to cardiac muscle.
Peristaltic movement does not need autonomic stimulation, but this does increase (parasympathetic) or decrease (sympathetic) activity.

Exocrine secretions of pancreas
The Pancreas secretes bicarbonate buffer into the duodenum from duct cells leading fromsecretory units called acini. Secretions bring pH up to about 7.

Cells in the acini secrete a number of proteases into the duodenum, namely
trypsinogen, chymotrypsinogen and procarboxypeptidase.

Enzyme cascade
Enterokinase produced by small intestine (located in the duodenum brush border) activates trypsinogen.
Trypsin in turn activates trypsinogen, chymotrypsinogen and procarboxypeptidase to form the active enzymes
trypsin, chymotrypsin and carboxypeptidase.
Carboxypeptidase and another brush border enzyme aminopeptidase are endopeptidases.

Pancreas also secretes amylase for carbohydrate breakdown.
Pancreas also secretes lipases for lipid breakdown.
Pancreas also secretes nucleases for nucleic acid breakdown.

The gall bladder secretes bile to emulsify fats.
Bile produced by liver and stored in gall bladder.
Bile salts are recycled, absorbed in small intestine and returned to liver (entero hepatic circulation).

The Liver
The liver has a rolle in digestion with the production of bile and is important in removing toxins from our blood. Blood from the intestine flows via the hepatic portal system to the liver before returning to the heart.
Biologically active molecules such as hormones as well as toxins are broken down or modified by enzymes associated with hepatic cells and excreted in bile.

Other compounds are inactivated or modified and stay in the blood to be filtered in the kidneys (e.g. ammonia converted to urea).
Kupffer cells in the liver use phagocytosis to and digest some compounds.

Some hormones such as estrogen and progesterone are removed by the liver and secreted in bile but reabsorbed in the intestine.
Reabsorption depends on breakdown of hormone complex by bacteria.
If antibiotics are taken, bacteria are killed and less hormone reabsorbed;
hence antibiotics can reduce the effectiveness of birth control pill.

Most absorption takes place in the ileum and jejunum of the small intestine.

The Large intestine
Mainly water and inorganic ion absorption and compaction of feces.
About 9 liters of water per day are ingested and secreted by the stomach and small intestine to make chyme and keep it moving along the gastrointestinal (GI) tract.
About 500 ml per day gets to the large intestine and less than about 100ml is excreted.

Dysentary and other forms of diarrhea are one of the leading causes of infant death.
It is very difficult to replace fluid secreted in the GI tract if it is not reabsorbed.
We normally only drink 1-2 liters of water per day.

Large bacterial community - necessary for normal function (includes E. coli).
Bacteria breakdown some cellulose (fiber) that cannot be digested by humans.
Bacteria synthesize vitamin K and folic acid that is absorbed.

From the large intestine, feces enter the rectum.
Stretch receptors monitor levels and stimulate the defecation reflex which can be overidden by the central nervous system.
Anal sphincter under autonomic and somatic nervous control.

Control of digestive secretions
Enzyme secretion is largely controlled by endocrine secretions from cells in the gastric mucosa.
Nervous control also plays a part and the thought of food or the smell of food can induce salivary secretions in the mouth and some gastric secretion. This is called the cephalic stage.
Secretion is achieved via vagus nerve stimulation (parasympathetic ns).

Gastric stage.
As food enters the stomach mechanoreceptors and chemoreceptors are stimulated.
Short polypeptides and amino acids stimulate chief cells to secrete pepsinogen and parietal cells to secrete HCl.They also stimulate G cells in the stomach to secrete the hormone gastrin.

Gastrin stimulates pepsinogen and HCl secretion also. Pepsinogen is involved in a positive feedback system.
Glucose in the stomach has no effect on gastric secretion and lipids inhibit gastric secretion.
Negative feedback controls the system - as pH in stomach drops gastrin secretion is inhibited, stopping completely at pH of 1.

HCl secretion is also stimulated by paracrine secretion of histamine from ECL (enterochromaffin-like) cells. ECL cells are stimulated by the ACh from the parasympathetic nervous system and gastrin.
Somatostatin from D cells inhibit HCl secretion.

Intestinal phase
As chyme enters the duodenum its presences stimulates chemoreceptors, mechanoreceptors and osmoreceptors to stimulate release of enterogastrones from cells in the wall of the duodenum and jejunum.

Secretin
Falling pH stimulate mucosal cells to secrete the hormone secretin. Secretin acts on duct cells of the pancreas to release bicarbonate rich pancreatic juice.
Secretin also stimulates the liver to increase secretion of bile.

Cholecystokinin
Lipids in the duodenum stimulate release of the hormone cholecystokinin (CCK).
CCK stimulates acinar cells in the pancreas to secrete digestive enzymes and contraction of muscle in the gall bladder to secrete bile.

Secretin and CCK are cross reactive and potentiate the action of each other.

Glucose-dependent insulinotropic peptide
Glucose, lipids, acid and distension in the duodenum also stimulate release of Glucose-dependent insulinotropic peptide, GIP, (an enterogastrone) that inhibits gastric secretion and motility. GIP also stimulates the release of insulin from the pancreas.

Enteric Nervous System
There are about the same number of nerve cells in the enteric nervous system as in the spinal cord.
Many structural similarities to the CNS like interneurons, and large numbers of glial cells and acts with some independence (some people call it the enteric brain).
Controls motility of chyme through the system.
Reflex systems react to stretch and chemicals.

The enteric nervous system integrates the motility throughout the GI tract
examples:
ileogastric reflex - distension of the ileum inhibits gastric activity
intestino/intestinal reflex - overdistension in one section causes relaxation in other parts of the intestine.

Lipoproteins
Chylomicrons, that first transport lipids from the intestine are lipoproteins.
Lipoproteins are large particles containing triglycerides, cholesterol and other fatty acids on the inside and phospholipids (and other amphipathic lipids) and proteins on the outside.
Proteins and amphipathic lipids allow the particle to dissolve in water and act as sites for enzyme and receptor binding.

The liver synthesizes lipoproteins (from stored or manufactured lipids) to distribute lipids via the blood.
Liver produces Low Density Lipoproteins, LDLs, so called because of the high proportion of low density lipids.
As LDLs circulate lipids are absorbed by cells, increasing their density and they are converted to IDLs and HDLs.
LDLs are thought to cause artherosclerotic plaques, cholesterol rich deposits in blood vessels.

HDLs can be broken down in the liver and their cholesterol secreted in bile.
Circulating HDLs absorb cholesterol from cells and other lipoproteins and transfer it back to the liver for excretion.
HDLs have been called good cholesterol and LDLs bad cholesterol because of their probable role in heart disease.
The ratio of HDLs/LDLs can be increased by reduced intake if saturated fats, regular exercise, quit smoking, and weight reduction.

Vitamins
Vitamins are organic molecules needed in very small quantities. They are ingested in their absorptive form and need no digestion.
Hydrophobic vitamins (A, D, E, K) are absorbed along with other lipids.
Hydrophilic vitamins need transporter proteins for absorption.
Vitamin B12 needs intrinsic factor secreted by parietal cells in the stomach for absorption in the ileum.

Clinical questions.

What is the cause of lactose intoleanc?

What is diverticulitis? Is diet a contributor to this problem?

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This webpage was created by Peter King. Please contact the the author with comments at pking@fmarion.edu.
Last edited July 20, 2010.
http://people.fmarion.edu/pking/humanphys/digestion.html
copyright Peter King.