THE STOMACH

Phosphorus works in the stomach to stabilize sugars and activate starches by the twofold process of phosphorylation. Phosphorus in conjunction with HCl, pepsin, zinc, and vitamin C via the thymus helps in the:

1. Stabilization of sugar-simple sugars are easily oxidized (combusted) before they reach the liver, resulting in low sugar levels. Pepsin stabilizes these simple sugars, so they can be transferred to the liver for storage.

2. Activation of starches-HCl is necessary to breakdown oily carbohydrates (grains), which are difficult to oxidize (combust), thus making them readily available for oxidation.

The above two mechanisms establish an HCl-pepsin balance in the stomach for proper pH digestion.

The presence of both HCl and pepsin in the stomach are critical for preparing carbohydrates and proteins for further digestion in the small intestines. Phosphorus indicates the amount of acid balance in the body. It does this by regulating secretions of HCl and pepsin in the stomach by the foods you eat. For example, when you eat foods that are high in phosphoric acid, there will be a release of pepsin to neutralize the acid. On the other hand, foods low in phosphoric acid content will cause large amounts of HCl to be released. Phosphorus then carries carbohydrates across the intestinal wall for absorption by the liver. Phosphorus also affects the intrinsic factor function by releasing alkaline B vitamins into inorganic foods, converting them into organic foods for storage in the liver sinusoids.

Patients that have an acid pH in their stomach should avoid excessive amounts of acid forming foods such as meats, dairy, grains and junk foods.

Patients that have an alkaline pH should avoid excessive amounts of alkaline forming foods such as fruits and vegetables.

Diet has a dramatic affect on the acidity or alkalinity of the stomach and is usually the culprit in stomach conditions.

The 3 Phases Of Gastric Secretion

1. The Cephalic Phase- which is the result of hunger, sight, smell and thought about food neurologically controlled by the cerebral cortex that project to appetite centers in the amygdala or hypothalamus. This phase accounts for 1/5th of the digestive juices produced.

2. The Gastric Phase- when the food enters the stomach it excites long vasovagal and local enteric nerves that stimulate the release of gastric juices accounting for 2/3rds of the 1500 ml’s released daily.

3. The Intestinal Phase – once the food enters the duodenum, it triggers the release of gastrin from the intestinal mucosa thus inhibiting the release of gastric juices. The presence of food in the small intestines initiates an enterogastric reflex, which also inhibits gastric secretions. The presence of secretin and cholecystokinin are responsible for pancreatic enzyme release. Cholecystokinin releases bile via the gallbladder and also inhibits gastric function. Acids, protein by-products, gastric inhibitory peptide, vasoactive intestinal polypeptide, and somatostatin all inhibit gastric secretions. Since the stomach is poor at absorption, very little takes place. It is only when you reach the small intestines that you find folds known as valvulae conniventes, which increase the surface area of the small intestines 3 fold. Extending from these conniventes are small projections called villi, which increase the absorption another 10 fold. These villi are close together and their outer epithelial cells form a brush border protruding into the chyme. This increases the absorptive power another 600 fold. This makes the surface of the small intestines 250 sq. meters (About the size of a tennis court). The absorptive capacity of the small intestines is astounding. It can absorb several kilograms of carbohydrates, 500-1000 grams of fat (20-40 ounces), 500-700 grams (20-28 ounces) of protein, and 20 or more liters of water daily.

There are four types of glands that are found in the gastrointestinal tract:

1. Salivary cells are found in the mouth, pancreas, and the liver

2. Mucous glands- Mucous contains, water, electrolytes, glycoproteins, and HCO3

ions. The function of mucous is to adhere tightly to the food while it coats the

intestinal wall. Mucous prevents food from contacting the mucosa. Mucous also

causes fecal particles to adhere together to form a mass. Mucous is also very

resistant to digestive juices, and can buffer acids or alkaline enzymes. The

esophagus also secretes mucous. The mucous glands secrete mucous in response

to vagal stimulation, gastrointestinal enzymes, and irritating factors. Mucous glands

that are in the upper duodenal area between the pylorus and papilla of vata are

called “Brunner’s glands”. Crypts of Lieberkuhn are found in the small intestines.

3. Tubular cells- are found in the stomach and are of 2 types: the oxyntic or gastric and the pyloric. The first, oxyntic, are your parietal and chief cells. The parietal cells secrete HCl, intrinsic factor for B12 absorption, and histamine. The chief cells secrete pepsinogen, intrinsic factor and mucous. The second type of tubular gland is called the pyloric gland. The pyloric glands mainly secrete mucous

but also pepsinogen and gastrin. The oxyntic glands are located in the body and fundus of the stomach comprising 80% of the stomach; the pyloric glands are found in the antral portion of the stomach. These tubular cells are also found in the upper part of the small intestines. Pepsinogen, which is not reactive, is activated and transformed into pepsin by coming in contact with HCl. Pepsin is a proteolytic

enzyme that is highly reactive in an acid media between (1.8-3.5). Therefore, both HCl and pepsin are responsible for protein digestion. Other enzymes of the stomach include gastric lipase and amylase; both are extremely weak and play a minor role in the digestion of fats and starches. Gelatinase, another enzyme, is responsible for liquification of proteoglycans found in meat. The stomach also secretes intrinsic factor, which is responsible for B12 absorption in the ileum.

B12 is responsible for red blood cell maturation. Gastric secretions have a pH of 1.0-3.5.

4. The stomach also secretes gastric amylase and lipase.

The Neurotransmitters Affecting Gastric Secretions Are:

1. Acetylcholine-which is responsible for pepsinogen via peptic cells, gastrin via gastric cells, HCl via parietal cells and mucous secretions.

2. Gastrin (2 types G17 and G34) named for the number of amino acids that make them up, and histamine (an amino acid derivative) both stimulate HCl production.

When gastric or acetylcholine are present histamine has a much stronger effect on acid production. All of these neurotransmitters activate receptor sites on secretory cells, which stimulate the secretory process. Amino acids, caffeine and alcohol can also stimulate gastric secretory activity.

Neural Control Of The Gastrointestinal System

The GI tract is controlled by:

A. Reflex activity between the brain stem (vagus nerve dorsal motor nuclei), such as the stomach motor and secretory activity, pain and strong powerful colonic contractions.

B. The spinal cord via the autonomic nervous system. The sympathetic division extends from T5-L3 forming the celiac and mesenteric plexuses and the sympathetic chain ganglion, which inhibits peristalsis and digestive secretions by the inhibition of the myenteric and submucosal plexus with norepinephrine. Usually, they control long range communication between the stomach, small intestine, ileocecal valve and the colon, by controlled slowing or speeding up of movement of food and fecal material.

C. The parasympathetic outflow division originates from S1-S3 and stimulates the movement of fecal material and reabsorption of H2O and electrolytes. Remember that almost all sympathetic or parasympathetic activity is afferent in nature. This means that distention, mucosal irritation from foods, drugs, preservatives, pH etc. send afferent messages to the brain stem initiating the proper course of action to occur.

D. The GI tract has its own nervous system called the enteric nervous system and is found in the gut wall extending from the esophagus to the anus (100 million neurons are the number of neurons in the spinal cord). The enteric nervous system releases the following neurotransmitters: acetylcholine, norepinephrine, ATP, serotonin, dopamine, cholecystokinin, substance P, vasoactive intestinal polypeptide, somatostatin, and leu-enkephalin. Acetylcholine stimulates intestinal activity norepinephrine inhibits intestinal activity.

The enteric nervous system is composed of 2 plexuses

1. myenteric plexus (Auerbach’s) found between the circular and longitudinal fibers and controls peristaltic movement. The myenteric plexus is composed of linear chains of interconnecting neurons. When stimulated it increases:

• Tonic contractions

• Rhythmic contractions

• Velocity of conduction

• Rate of rhythm

· · ·

Please note that the myenteric plexus does play a role in inhibition of the pyloric sphincter and the ileocecal valve.

2. Submucosal plexus (Meissner’s plexus) is found in the submucosa and is responsible for digestive secretions and blood flow. The purpose of the enteric nervous system is to control peristalsis and digestive secretions short range over small distances. This is most beneficial since the body uses a finer control over the local digestive process.

Digestion And Absorption In The Gastrointestinal Tract

Carbohydrate Digestion- There are 3 major sources of carbohydrates in the diet

Sucrose, a disaccharide known as cane sugar

Lactose, a disaccharide known as milk sugar

Starches (grains), which are long polysaccharides

When monosaccharides form disaccharides, hydrogen is removed from one monosaccharide and a hydroxyl group is removed from the other monosaccharide, forming water in a process (condensation). When disaccharides split into monosaccharides the process is called hydrolysis (the addition of water to form the 2 monosaccharides). Humans cannot digest cellulose.

Carbohydrate digestion starts in the mouth via an alpha amylase known as ptyalin, secreted by the parotid glands. This enzyme hydrolyzes starches into maltose and other small polymers of glucose (3-9 glucose molecules long.). 3-5% of all starches are digested in the mouth. As the food enters the stomach ptyalin continues to digest the carbohydrates so that within 1 hour, upon entering the stomach, most of the carbohydrates are converted into maltose. When the pH falls below 4.0 ptyalin starts to become inactive. By the time the chyme reaches the duodenum and jejunum, pancreatic amylase, which is much more potent then ptyalin (more concentrated), converts the remaining polymers into maltose.

In the lining membranes of the intestinal lumen (microvilli brush border) there are four enzymes produced:

Lactase, which splits lactose into galactose and glucose

Sucrase, which splits sucrose into fructose and glucose

Maltase, which splits maltose into glucose.

Alpha Dextrinase, which splits all of the above as well as dextrins

2. Protein Digestion-Protein digestion starts in the stomach via pepsin. Pepsin is also important for digesting collagen, an albuminoid found in meats. Pepsin is most active at a pH of 2-3. The HCl produced by the body has a pH of .8. When proteins leave the stomach they are mostly in the form of proteases, peptones, and large polypeptides. When the chyme reaches the small intestines the pancreatic enzymes trypsin and chymotrypsin split proteins into small peptides and carboxypolypeptidase then split a small percentage of these into amino acids. The bulk of the peptides are broken down by the multiple peptidases located in the brush border of the intestinal membrane.

The most important peptidases are aminopolypeptidase and several dipeptidases. These split the proteins down to di and tri-peptides, which enter the microvilli membrane into the interior of the epithelial cell where other peptidases break up the remaining di and tripeptides into amino acids to be absorbed into the blood stream. Please note that di, tri, and polypeptides can still enter the blood stream and can cause allergic reactions. 99 % of all protein is absorbed as amino acids.

3. Fat Digestion The most abundant fat in the diet is in the form of triglycerides, which contains a glycerol nucleus and 3 fatty acids (stearic, and palmitic acid, which are saturated and oleic acid which is unsaturated). All 3 come from animal and not plant origin. The usual diet contains phospholipids, cholesterol and cholesterol esters.

Cholesterol is formed in the liver from degraded products of fatty acid molecules, which give cholesterol its fatty characteristics. Fat (butterfat) is digested in the stomach via gastric lipase (tributyrase) in very small amounts. 99% of fat digestion takes place in the intestines via bile. Bile contains bile salts and a phospholipid known as lecithin in the form of ionized sodium salts. Bile salts have the ability to form micelles, small globules of fat attached to the bile salt. This occurs because the sterol portion of the bile salt is highly soluble in fat and a polar portion of the bile salts and lecithin are highly soluble in water. This reducing and changing the polarity reduces the interfacial tension between the fat cells so digestive enzymes can continue to break down the fat. This increases the total surface area of the fat a 1000 fold. Pancreatic lipase is responsible for splitting 99% of the triglycerides into 3 fatty acids and 2 monossachrides.

Cholesterol, its ester (cholesterol +1 molecule of a fatty acid) and phosopholipids (via cholesterol ester hydrolase and phospholipidase respectively) are broken down via hydrolysis of the fatty acids from their molecular structures. The bile salts, when attached to lipids create micelles, which are highly charged and increase the absorption of these fatty acids, glycerol, free cholesterol and the remaining portion of the phospholipids. Please note that without bile salts much of the fat will be blocked from entering the blood stream.

THE GALLBLADDER

The purpose of the gallbladder is to store bile, which was produced via the liver (600-1200 mL are produced daily) and received the precursors from the spleen and the adrenals. Biliverdin and bilirubin are pigments that are used in red blood cell production. When red blood cells reach the 120-day mark, they are broken down via the spleen and tissue macrophages (reticuloendothelial cells). These pigments are released and utilized to form bile.

Hemoglobin is also split into globin and heme. The heme is transferred in the blood with transferrin to form with the pyrrole nuclei. Biliverdin is then reduced to form bilirubin. The salts that help produce bile for emulsification of fat are produced via the adrenal glands. The precursor of bile salts is cholesterol, which is also produced via the liver and then converted into cholic acid or chendodeoxycholic acid equally. 80% of all cholesterol is converted into these two acids. These acids combined with glycine and taurine to form glyco and tauro conjugated bile acids, with the salts of the acids being secreted in the bile. The release of bile via gallbladder contractions is caused by cholecystokinin.

The purpose of bile is three-fold:

• The first is to transform a fat into soap via saponification (oxidation of fat), which leads to emulsification. In order for the salts to be infused into the fat, lecithin must be present. This decreases the surface tension of the fat molecule allowing agitation to break up the fat into small sizes. Therefore, the components of bile are lecithin, which are choline and inositol, cholesterol and bile salts.

• The second thing bile salts do is to help absorb fatty acids, monoglycerides, cholesterol and other lipids by forming minute complexes called “micelles.” These are highly soluble, highly charged and are easily absorbed, increasing absorption of fat by 40 percent.

• The third purpose of bile is to excrete waste products, such as excessive cholesterol produced by the liver and bilirubin, which is the end product of hemoglobin degradation.

The following tests determine liver function:

1. SGPT (SERUM GLUTAMIC PYRUVIC TRANSAMINASE) (ALT) -SGPT has a maximum concentration in the liver sinusoid membranes. SGPT is also found in large amounts in the kidneys, heart and skeletal muscle. SGPT is the primary Krebs cycle expresser. It occurs as the result of the catabolic release of fat. Pyruvates are those substances that balance fats in an anti-oxidant media. The oxygen from the iron, and the antioxidant media from fat, which is the lubricator vitamin known as vitamin A, is balanced by pyruvates. Vitamin A is also used in the sinusoids of the lungs, spleen, kidney, sinuses and lymphatic tissue.

SGPT exists in the blood serum as a consequence of substances being released by the fatty membranes of the liver sinusoids and lymphatic ducts. The liver sinusoids store food while the lymphatic ducts house toxins. Picture a layer of vitamin A that holds food or toxins in the cell. Now, as that layer of fat (vitamin A) is being burned off, oxidized via iron, foods or toxins are released from the sinusoids or lymphatic in a controlled manner, allowing foods or toxins to be released and directed to the next destination.

SGPT shows the fat and the fatty acid storage ability that takes place in the liver. SGPT is the primary kreb cycle expresser, which occurs as the result of the release of catabolic fats from the liver.

2. TOTAL IRON-is the indicator of the process of oxidation vs. the antioxidation (fat). This occurs in the liver, as mentioned above.

3. GGTP-SERUM GAMMA GLUTAMYL TRANSFERASE (TRANSPEPTIDASE) is another liver enzyme test that is more concerned with liver/gallbladder/pancreatic problems and alcoholism. SGPT is more concerned with the release of foodstuffs from the liver.

4. TOTAL BILIRUBIN-as mentioned above, bilirubin is formed by the destruction of hemoglobin by the liver (kupfer cells), bone marrow and spleen. Impaired production or excretion of hemoglobin results in jaundice/liver disease. Total bilirubin is made up of direct and in-direct bilirubin. Direct bilirubin is what is called the post hepatic form, which has already been reacted on by the liver (conjugated). The elevation is usually caused by biliary obstruction. Indirect bilirubin is the pre-hepatic form, which has not been reacted on by the liver (unconjugated) and elevation occurs during liver failure. As you can see, SGPT and total iron are liver function tests, and GGTP and total bilirubin are related more to gallbladder dysfunction.

THE PANCREAS

The pancreas is composed of a head and a tail. The purpose of the pancreatic head is used to secrete pancreatic enzymes. The purpose of the pancreatic tail is to produce insulin. For more information check the pancreatic head and tail sections.

THE STOMACH

Phosphorus works in the stomach to stabilize sugars and activate starches by the twofold process of phosphorylation. Phosphorus in conjunction with HCl, pepsin, zinc, and vitamin C via the thymus helps in the:

1. Stabilization of sugar-simple sugars are easily oxidized (combusted) before they reach the liver, resulting in low sugar levels. Pepsin stabilizes these simple sugars, so they can be transferred to the liver for storage.

2. Activation of starches-HCl is necessary to breakdown oily carbohydrates (grains), which are difficult to oxidize (combust), thus making them readily available for oxidation.

The above two mechanisms establish an HCl-pepsin balance in the stomach for proper pH digestion.

The presence of both HCl and pepsin in the stomach are critical for preparing carbohydrates and proteins for further digestion in the small intestines. Phosphorus indicates the amount of acid balance in the body. It does this by regulating secretions of HCl and pepsin in the stomach by the foods you eat. For example, when you eat foods that are high in phosphoric acid, there will be a release of pepsin to neutralize the acid. On the other hand, foods low in phosphoric acid content will cause large amounts of HCl to be released. Phosphorus then carries carbohydrates across the intestinal wall for absorption by the liver. Phosphorus also affects the intrinsic factor function by releasing alkaline B vitamins into inorganic foods, converting them into organic foods for storage in the liver sinusoids.

Patients that have an acid pH in their stomach should avoid excessive amounts of acid forming foods such as meats, dairy, grains and junk foods.

Patients that have an alkaline pH should avoid excessive amounts of alkaline forming foods such as fruits and vegetables.

Diet has a dramatic affect on the acidity or alkalinity of the stomach and is usually the culprit in stomach conditions.

The 3 Phases Of Gastric Secretion

1. The Cephalic Phase- which is the result of hunger, sight, smell and thought about food neurologically controlled by the cerebral cortex that project to appetite centers in the amygdala or hypothalamus. This phase accounts for 1/5th of the digestive juices produced.

2. The Gastric Phase- when the food enters the stomach it excites long vasovagal and local enteric nerves that stimulate the release of gastric juices accounting for 2/3rds of the 1500 ml’s released daily.

3. The Intestinal Phase – once the food enters the duodenum, it triggers the release of gastrin from the intestinal mucosa thus inhibiting the release of gastric juices. The presence of food in the small intestines initiates an enterogastric reflex, which also inhibits gastric secretions. The presence of secretin and cholecystokinin are responsible for pancreatic enzyme release. Cholecystokinin releases bile via the gallbladder and also inhibits gastric function. Acids, protein by-products, gastric inhibitory peptide, vasoactive intestinal polypeptide, and somatostatin all inhibit gastric secretions. Since the stomach is poor at absorption, very little takes place. It is only when you reach the small intestines that you find folds known as valvulae conniventes, which increase the surface area of the small intestines 3 fold. Extending from these conniventes are small projections called villi, which increase the absorption another 10 fold. These villi are close together and their outer epithelial cells form a brush border protruding into the chyme. This increases the absorptive power another 600 fold. This makes the surface of the small intestines 250 sq. meters (About the size of a tennis court). The absorptive capacity of the small intestines is astounding. It can absorb several kilograms of carbohydrates, 500-1000 grams of fat (20-40 ounces), 500-700 grams (20-28 ounces) of protein, and 20 or more liters of water daily.

There are four types of glands that are found in the gastrointestinal tract:

1. Salivary cells are found in the mouth, pancreas, and the liver

2. Mucous glands- Mucous contains, water, electrolytes, glycoproteins, and HCO3

ions. The function of mucous is to adhere tightly to the food while it coats the

intestinal wall. Mucous prevents food from contacting the mucosa. Mucous also

causes fecal particles to adhere together to form a mass. Mucous is also very

resistant to digestive juices, and can buffer acids or alkaline enzymes. The

esophagus also secretes mucous. The mucous glands secrete mucous in response

to vagal stimulation, gastrointestinal enzymes, and irritating factors. Mucous glands

that are in the upper duodenal area between the pylorus and papilla of vata are

called “Brunner’s glands”. Crypts of Lieberkuhn are found in the small intestines.

3. Tubular cells- are found in the stomach and are of 2 types: the oxyntic or gastric and the pyloric. The first, oxyntic, are your parietal and chief cells. The parietal cells secrete HCl, intrinsic factor for B12 absorption, and histamine. The chief cells secrete pepsinogen, intrinsic factor and mucous. The second type of tubular gland is called the pyloric gland. The pyloric glands mainly secrete mucous

but also pepsinogen and gastrin. The oxyntic glands are located in the body and fundus of the stomach comprising 80% of the stomach; the pyloric glands are found in the antral portion of the stomach. These tubular cells are also found in the upper part of the small intestines. Pepsinogen, which is not reactive, is activated and transformed into pepsin by coming in contact with HCl. Pepsin is a proteolytic

enzyme that is highly reactive in an acid media between (1.8-3.5). Therefore, both HCl and pepsin are responsible for protein digestion. Other enzymes of the stomach include gastric lipase and amylase; both are extremely weak and play a minor role in the digestion of fats and starches. Gelatinase, another enzyme, is responsible for liquification of proteoglycans found in meat. The stomach also secretes intrinsic factor, which is responsible for B12 absorption in the ileum.

B12 is responsible for red blood cell maturation. Gastric secretions have a pH of 1.0-3.5.

4. The stomach also secretes gastric amylase and lipase.

The Neurotransmitters Affecting Gastric Secretions Are:

1. Acetylcholine-which is responsible for pepsinogen via peptic cells, gastrin via gastric cells, HCl via parietal cells and mucous secretions.

2. Gastrin (2 types G17 and G34) named for the number of amino acids that make them up, and histamine (an amino acid derivative) both stimulate HCl production.

When gastric or acetylcholine are present histamine has a much stronger effect on acid production. All of these neurotransmitters activate receptor sites on secretory cells, which stimulate the secretory process. Amino acids, caffeine and alcohol can also stimulate gastric secretory activity.

Neural Control Of The Gastrointestinal System

The GI tract is controlled by:

A. Reflex activity between the brain stem (vagus nerve dorsal motor nuclei), such as the stomach motor and secretory activity, pain and strong powerful colonic contractions.

B. The spinal cord via the autonomic nervous system. The sympathetic division extends from T5-L3 forming the celiac and mesenteric plexuses and the sympathetic chain ganglion, which inhibits peristalsis and digestive secretions by the inhibition of the myenteric and submucosal plexus with norepinephrine. Usually, they control long range communication between the stomach, small intestine, ileocecal valve and the colon, by controlled slowing or speeding up of movement of food and fecal material.

C. The parasympathetic outflow division originates from S1-S3 and stimulates the movement of fecal material and reabsorption of H2O and electrolytes. Remember that almost all sympathetic or parasympathetic activity is afferent in nature. This means that distention, mucosal irritation from foods, drugs, preservatives, pH etc. send afferent messages to the brain stem initiating the proper course of action to occur.

D. The GI tract has its own nervous system called the enteric nervous system and is found in the gut wall extending from the esophagus to the anus (100 million neurons are the number of neurons in the spinal cord). The enteric nervous system releases the following neurotransmitters: acetylcholine, norepinephrine, ATP, serotonin, dopamine, cholecystokinin, substance P, vasoactive intestinal polypeptide, somatostatin, and leu-enkephalin. Acetylcholine stimulates intestinal activity norepinephrine inhibits intestinal activity.

The enteric nervous system is composed of 2 plexuses

1. myenteric plexus (Auerbach’s) found between the circular and longitudinal fibers and controls peristaltic movement. The myenteric plexus is composed of linear chains of interconnecting neurons. When stimulated it increases:

• Tonic contractions

• Rhythmic contractions

• Velocity of conduction

• Rate of rhythm

· · ·

Please note that the myenteric plexus does play a role in inhibition of the pyloric sphincter and the ileocecal valve.

2. Submucosal plexus (Meissner’s plexus) is found in the submucosa and is responsible for digestive secretions and blood flow. The purpose of the enteric nervous system is to control peristalsis and digestive secretions short range over small distances. This is most beneficial since the body uses a finer control over the local digestive process.

Digestion And Absorption In The Gastrointestinal Tract

Carbohydrate Digestion- There are 3 major sources of carbohydrates in the diet

Sucrose, a disaccharide known as cane sugar

Lactose, a disaccharide known as milk sugar

Starches (grains), which are long polysaccharides

When monosaccharides form disaccharides, hydrogen is removed from one monosaccharide and a hydroxyl group is removed from the other monosaccharide, forming water in a process (condensation). When disaccharides split into monosaccharides the process is called hydrolysis (the addition of water to form the 2 monosaccharides). Humans cannot digest cellulose.

Carbohydrate digestion starts in the mouth via an alpha amylase known as ptyalin, secreted by the parotid glands. This enzyme hydrolyzes starches into maltose and other small polymers of glucose (3-9 glucose molecules long.). 3-5% of all starches are digested in the mouth. As the food enters the stomach ptyalin continues to digest the carbohydrates so that within 1 hour, upon entering the stomach, most of the carbohydrates are converted into maltose. When the pH falls below 4.0 ptyalin starts to become inactive. By the time the chyme reaches the duodenum and jejunum, pancreatic amylase, which is much more potent then ptyalin (more concentrated), converts the remaining polymers into maltose.

In the lining membranes of the intestinal lumen (microvilli brush border) there are four enzymes produced:

Lactase, which splits lactose into galactose and glucose

Sucrase, which splits sucrose into fructose and glucose

Maltase, which splits maltose into glucose.

Alpha Dextrinase, which splits all of the above as well as dextrins

2. Protein Digestion-Protein digestion starts in the stomach via pepsin. Pepsin is also important for digesting collagen, an albuminoid found in meats. Pepsin is most active at a pH of 2-3. The HCl produced by the body has a pH of .8. When proteins leave the stomach they are mostly in the form of proteases, peptones, and large polypeptides. When the chyme reaches the small intestines the pancreatic enzymes trypsin and chymotrypsin split proteins into small peptides and carboxypolypeptidase then split a small percentage of these into amino acids. The bulk of the peptides are broken down by the multiple peptidases located in the brush border of the intestinal membrane.

The most important peptidases are aminopolypeptidase and several dipeptidases. These split the proteins down to di and tri-peptides, which enter the microvilli membrane into the interior of the epithelial cell where other peptidases break up the remaining di and tripeptides into amino acids to be absorbed into the blood stream. Please note that di, tri, and polypeptides can still enter the blood stream and can cause allergic reactions. 99 % of all protein is absorbed as amino acids.

3. Fat Digestion The most abundant fat in the diet is in the form of triglycerides, which contains a glycerol nucleus and 3 fatty acids (stearic, and palmitic acid, which are saturated and oleic acid which is unsaturated). All 3 come from animal and not plant origin. The usual diet contains phospholipids, cholesterol and cholesterol esters.

Cholesterol is formed in the liver from degraded products of fatty acid molecules, which give cholesterol its fatty characteristics. Fat (butterfat) is digested in the stomach via gastric lipase (tributyrase) in very small amounts. 99% of fat digestion takes place in the intestines via bile. Bile contains bile salts and a phospholipid known as lecithin in the form of ionized sodium salts. Bile salts have the ability to form micelles, small globules of fat attached to the bile salt. This occurs because the sterol portion of the bile salt is highly soluble in fat and a polar portion of the bile salts and lecithin are highly soluble in water. This reducing and changing of the polarity reduces the interfacial tension between the fat cells so digestive enzymes can continue to break down the fat. This increases the total surface area of the fat a 1000 fold. Pancreatic lipase is responsible for splitting 99% of the triglycerides into 3 fatty acids and 2 monossachrides.

Cholesterol, its ester (cholesterol +1 molecule of a fatty acid) and phosopholipids (via cholesterol ester hydrolase and phospholipidase respectively) are broken down via hydrolysis of the fatty acids from their molecular structures. The bile salts, when attached to lipids create micelles, which are highly charged and increase the absorption of these fatty acids, glycerol, free cholesterol and the remaining portion of the phospholipids. Please note that without bile salts much of the fat will be blocked from entering the blood stream.

LIVER

The liver has at least 500 separate functions. If we looked at the classification of these functions we could narrow them down to 2 classifications. The first classification would be one of food processing. The liver is responsible for changing inorganic food to organic food, via the process of denitrification, in which thyroxin is necessary. Lipid metabolism of cholesterol, triglycerides and phospholipids occurs mainly in the liver. Such is the case with carbohydrate, as well as lipoprotein metabolism.

1. CLASSIFICATION ONE-FOOD PROCESSING

For example, when it comes to carbohydrate metabolism the liver does the following:

• Causes gluconeogenesis from fats and proteins

• Acts as a storage center for glycogen and balances blood sugar by the method called “glucose buffer function.”

As far as fat metabolism is concerned, the liver does the following:

• Forms lipoproteins, phospholipids, and cholesterol, of which 80% is used to make bile salts. Both phospholipids and cholesterol are used to make cell membranes, hormones, and intracellular structures. The liver also converts carbohydrates and proteins into fats. The liver also oxidizes fatty acids quickly. Fat is quickly turned into glycerol and three fatty acids, and then through beta-oxidation, becomes acetyl coenzyme A, via the Kreb cycle. It is then sent to other cells in the form of acetoacetic acid, which cells convert back to acetyl coenzyme A.

As far as protein metabolism is concerned:

• The liver forms all major plasma proteins except for gamma globulins. The liver also forms fibrinogen, prothrombin and accelerator globulin.

As far as vitamins and minerals are concerned:

• The liver also stores vitamin A, D, and B12

• The liver also stores iron as ferritin, by using apoferritin to attach to the iron forming ferritin. When there is a decrease of iron in the blood, ferritin releases the iron from the liver.

According to Dr. Brockman, iodine is responsible for catabolism, which is a release of the foods from the liver sinusoids. Vanadium is responsible for anabolism, by storing foods in the liver sinusoids.

2. CLASSIFICATION TWO-IMMUNITY AND TOXIC REMOVAL-The endo-reticular portion, which is the most distal area, is responsible for blood filtration of all poisons, toxins, bacteria, virus, parasites, environmental pollutants, pesticides, industrial chemicals, food additives, metabolic wastes, excessive hormones, medications, and any and all filth that one can put into their body. At the present time, there are thought to be 200,000 foreign chemicals in the environment. The liver, through its various enzyme pathways, is responsible for neutralization of the various poisons.

The first system is the cytochrome P450 group of enzymes known to contain 500 different enzymes. This group of enzymes is also known as the “Phase 1” system. Phase 1 enzymes chemically oxidize substances into more toxic compounds. It is interesting to note that these intermediates can be very reactive and carcinogenic. The substrates that make up the cytochrome P450 group are thought to originate from steroids, sterols, and fatty acids.

The second system, known as the Phase 2 system, converts these substances into nontoxic and readily excreted substances. So, the cytochrome P450 group oxidizes a substance with oxygen, and the Phase 2 system often uses the oxygen site for further metabolism. The phase 2 conjugation pathway system is the addition of an endogenous substance, such as a carbohydrate derivative (glucuronic acid), or amino acids glycine and glutathione, or sulfate, to a foreign compound.

This conjugated compound is now less polar and less lipid soluble, thus facilitating excretion and reducing the likelihood of toxicity. There are three conjugation systems: glycine, sulfate, and glucuronides conjugation. The liver must identify food from toxins. It must program and reconstruct those substances that the thyroid has prepared.

Through the use of copper and iron (cytochromes), the liver tags the microbe or toxin. The iron is used to fight infection and for transportation for beneficial hosting. An example of this would be monocytes attacking a virus and engulfing it and transporting it away from the liver.

Copper is used to neutralize toxins. Once a substance leaves the liver, whether it is food, microbe, or chemical poison, the process of oxidation starts. Iron or copper, prior to its proper destination, must not oxidize the substance. Antioxidants, such as cholesterol and triglycerides, surround the substance so that you can have sufficient time for oxidation and proper combustion of the surrounded substance at the proper time.

Premature oxidation is what allows toxins, microbes, food and metabolic wastes to be released into the system before it reaches its destination.

THE PANCREAS

The pancreas is composed of a head and a tail. The purpose of the pancreatic head is used to secrete pancreatic enzymes. The purpose of the pancreatic tail is to produce insulin. I will first discuss the pancreatic head.

THE PANCREATIC HEAD

The pancreatic head synthesizes and produces the following enzymes, which are released by the acini cells:

1. Trypsinogen

2. Chymotrypsinogen

3. Pro carboxy polypeptidase

All are enzymatically inactive until they are activated by enterokinase when they enter the intestinal tract.

Once these enzymes are activated, they are called trypsin and chymotrypsin, which cleave proteins into peptides. Carboxypolypeptidase, which is now the activated form of pro carboxy polypeptidase, then splits these peptides into amino acids. Pancreatic lipases include cholesterol esterase, which hydrolyzes cholesterol esters and phospholipase, which splits fatty acids from phospholipids.

The pancreas also secretes pancreatic amylase, which breaks down carbohydrates.

Bicarbonate ions (sodium) also make up a portion of pancreatic secretions, which alkalize the gastric secretions of the stomach. If necessary, bicarbonate ions can be increased by five times the normal amount. There are four stimuli of pancreatic secretions:

1. The first is acetylcholine via the vagus nerve

2. The second is gastrin produced by the stomach

3. The third is cholecystokinin secreted by the duodenum, which is responsible for pancreatic enzyme release

4. The fourth is secretin, which increases sodium bicarbonate ions

The primary job of pancreatic enzymes is to oxidize fatty acids (complex sugars) through the use of chromium via amylase. Chromium is trivalent and is very acceptable to oxygen. Chromium, therefore, causes immediate oxidation (injects oxygen between the oil and sugar of the fatty acid causing pre-combustion, which readies the fatty acids for combustion and energy exchange. The head of the pancreas regulates the most alkaline substance, which is starch, and when there is an increased alkalinity of the blood, there is an increase in fatty acid oxidation via chromium.

It is worth mentioning that there are three steps necessary in the breakdown of fatty acids, which are as follows:

1. Fatty acids are first prepared via ptyalin in the saliva, (which contains large amounts of potassium), activated by having the mumps.

2. The second step is through aerobic enzymation in the small intestines, which is the chromium oxidation step I just spoke about. According to Dr. Brockman having the chickenpox activates this step.

3. The final step is an anaerobic step, which occurs, between the liver-gallbladder and the head of the pancreas (duct of worsung) where trypsin and chymotrypsin are secreted. According to Dr. Brockman, this is stimulated or activated by having the measles.

The measles encourages the expression, appropriate potency, and types of pancreatic enzymes. Patients who continually contract the measles are trying to kick in their pancreas to release the pancreatic enzymes.

The following blood tests are used to determine pancreatic head conditions:

1. CALCIUM-besides bonding to lipoproteins, calcium also bonds to the oily portion of fatty acids. This is necessary if the fatty acids want to pass through the intestinal wall. If there is poor oxidation of fatty acids, then there will be a certain amount of calcium, which will be needed to bond to the fatty acids, decreasing the calcium levels in the blood.

2. LACTIC ACID DEHYDROGENASE (LDH)-is a glycolytic enzyme that functions as a catalyst in carbohydrate metabolism, which aids the pyruvic and lactic acid interchange. LDH is a byproduct of muscle metabolism. When sugar and water (fatty acid metabolism) are exchanged across a muscle cell interface, the byproduct left is called lactic acid. Lactic acid is also a byproduct of fatty acid metabolism via the alkalizing and oxidizing affects of the pancreatic head. When lactic acid combines with the venous blood (carbon dioxide), there is a hydrogen displacement. The lactic acid then bonds to a double hydrogen forming lactic acid dehydrogenase.

LDH is then a byproduct of carbohydrate and fatty acid metabolism. The organs and glands that that are most responsible for sugar and water interchange across the muscle cell interface are the pancreas and the posterior pituitary (via antidiuretic hormone.) LDH is found chiefly in the heart, kidneys, liver, skeletal muscles, as well as all tissues. LDH is a normal component of cerebral spinal fluid.

THE PARATHYROIDS

Located on the posterior portion of the thyroid are four-five parathyroid glands weighing 120 grams total, with an ellipsoidal shape having the dimensions of 6x5x2 millimeters. The blood supply for the parathyroids is the inferior thyroid artery. The chief cells, which are the major cells of the parathyroids, synthesize and secrete parathormone (PTH) (which is 84 amino acid’s long) that comes from a pre-proparathormone, which is 110 amino acids long.

Though calcium is the major factor controlling the secretion of PTH, secretion of newly synthesized PTH is from preformed pools of PTH, where cAMP only stimulates these pools. cAMP is the major regulator of PTH secretion. Beta-androgenic catecholamines, dopamine, secretin and prostaglandin E can activate adenylate cylclase and increase cAMP, thereby stimulating PTH regulation.

The basic function of PTH is to control calcium concentration in the extracellular fluid (ECF). Parathyroid hormone, calcitonin and calciferous are the principle calcitrope hormones. Sodium, calcium, and potassium play a central role in the transmission of information between cells.

Phosphates act as:

• Cytoplasmic buffers

• Participate in energy exchange

• Makeup membranes and nucleic acids

The bulk of calcium, phosphates, and magnesium in the body are found in the skeleton. RDA’s of calcium is between 8-1200 mgs, for magnesium 4-600 mgs and 8-1200 mgs for phosphate. Less than 2% of calcium, magnesium and phosphates are found in the plasma and extracellular fluid and are controlled in narrow limits. Steady states of calcium, magnesium and phosphorus approximate urine loss against intestinal absorption and skeletal mineral apposition against mineral absorption. Magnesium in the cells is complexed to phosphate, citrates and anions such as ATP, AMP, and ADP (such as MgATP2).

Phosphates are covalently incorporated into proteins, lipids, and nucleic acids. Many enzymes go thru dramatic shifts in activity via phosphorylation and dephosphorylation.

Ionized cellular calcium regulates secondary cell messengers. Calcium can increase in a cell due to electrical impulses, hormones, and intracellular signals. Calcium also interacts with proteins such as protein kinase C, and ion channels found in plasma membranes and the sarcoplasmic reticulum.

Parathormone levels elevate cell calcium levels in the renal tubules and the osteoblasts. Calcium is transported from the cytoplasm by exchange with sodium. Contracted striated muscle relaxes with rapid removal of calcium from the cytoplasm into the sarcoplasmic reticulum. Plasma membranes undergo many complex interactions with cellular calcium via membrane permeability and pump activity.

In erythrocytes, cellular calcium increases potassium permeability. Mitochondria contain most of the intracellular calcium. There are many cytoplasmic enzyme changes via calcium such as adenylate cylclase, guanylate cylclase, cAMP, ATPase and protein C kinase. Since calcium can regulate contractile proteins, it can affect striated muscle, secretory granule contraction, exocytosis, mitotic spindle function and ciliary beating.

Calcium concentrations can be reduced quickly via repetitive nerve stimulation. Albumin accounts for 70% of the protein binding of calcium. Magnesium bonds to the same site on the albumin molecule as calcium, but with a lower affinity, thereby having more magnesium in a diffusible form. Magnesium is also affected just the way calcium is to parathormone, and to a lesser degree calcitonin.

70 % of phosphates are bound to phospholipids and phosphoproteins and are also affected in and out of plasma compartments by parathormone, calcitonin, and calciferols.

PTH enhances phosphate secretion and inhibits sodium reabsorption in the proximal tubules. PTH stimulates both bone formation and reabsorption (catabolism and anabolism) via influencing osteoclasts, osteoblasts, and osteocytes. PTH enhances synthesis of hyaluronate and inhibits citrate decarboxylation and collagen synthesis while it increases alkaline phosphatase levels.

Other affects of PTH include changes in blood flow, mitosis of lymphocytes, enhanced lipolysis and increased gluconeogenesis from the liver and kidney. PTH reacts with specific receptors on the bone and kidney (renal cortex) activating adenylate cylclase and intracellular messenger cAMP

According to Guyton’s Physiology on the physiology of calcium and phosphate “phosphates act as buffers, participate in energy exchange, and are an essential component of membranes and nucleic acids. 70 % of phosphates are bound to phospholipids and phosphoproteins.”

Phosphates do not affect PTH or calcitonin (CT) levels, but PTH and CT affect phosphate levels. The function of vitamin D and the formation of bone and teeth are all tied together in a common system, along with the two regulatory hormones parathyroid hormone (parathormone), calcitonin and the calciferols. In mammals, the bulk of calcium, phosphates and magnesium are found in the skeleton as hydroxyapatite. Less than 2% are found in the extracellular fluid.

Plasma calcium is used for clotting and kinin formation, regulates plasma membrane potential and exocytosis. As stated above, albumin accounts for 70% of the bound calcium. Magnesium also binds to albumin, and since it has a lower specificity for the receptors, it creates more free magnesium in the plasma. Calcium, magnesium, and phosphates continuously enter the plasma via the kidneys (intestinal brush borders) and the ruffled border of bones.

Calcium, phosphates, and magnesium are depressed in vitamin D deficiencies. Phosphates are reabsorbed by the proximal convoluted tubules due to PTH, and PTH also absorbs magnesium and calcium from the distal tubules. Calcium is poorly absorbed in the intestinal tract, as are most other bivalent cations. Calcium absorption can be dramatically affected by vitamin D, which has a potent effect on increased calcium absorption in the intestinal tract. In fact calcium, magnesium and phosphates are depressed in vitamin D deficiencies and increased with vitamin D excess. Calcium absorption is also increased by dietary sugars.

The D vitamins (calciferols) are steroid molecules of 4 rings. Calciferols are absorbed in the chylomicrons of the small intestines (60-90%) and are bound to alpha globulins. Vitamin D is also stored in the adipose tissue. It is not actually vitamin D, but a vitamin D compound that is formed between the liver and the kidneys, known as 1,2,5-dihydroxycholecalciferol. This 1,2,5-dihydroxycholecalciferol is also stimulated by parathyroid hormone. Another vitamin D compound that is important is D3 (cholecalciferol), found in the skin.

BONE FORMATION

Skeletal tissue consists of an extracellular matrix 55% organic and 45% inorganic and cells. The purpose on the skeletal system is to regulate the distribution of inorganic compounds, such as calcium, for the remodeling and the formation and reabsorption of the matrix.

There are 3 types of cells

1. Osteoblasts-derived from pre-osteoblasts from the mesenchyme. They are cuboid in shape, have a lot of Golgi apparatus for collagen processing, and lots of alkaline phosphatase. Osteoblasts are located in the bone-forming surface and are responsible for elaborating organic compounds from the extracellular matrix and the mineralized bone. The unmineralized matrix forms the osteoid zone and is separated from the mineralized bone via the calcification front. Osteoblasts form bone by the release of alkaline phosphatase, which increases the concentration of phosphate into the bone matrix.

2. Osteocytes-once osteoblasts, they are surrounded by an organic matrix and are now called osteocytes.

3. Osteoclasts-are also found on the bone surface. They are multinucleated, highly mobile moving along the bone surface reabsorbing bone. Osteoclasts break bone down. The cytoplasm contains abundant mitochondria, vacuoles, and lysosomes containing acid hydrolases such as carbonic anhydrate. Other cells found in bone are endothelial cells, fibroblasts, preosteoclasts, and preosteoblasts. Other inorganic components that make up the inorganic matrix are calcium, phosphate in a crystalline structure known as hydroxyapatite, with fluorine, sodium, potassium, magnesium and carbonate.

80% of the skeletal mass is made of cortical (compact) bone (long bones). Cortical bone is composed of packed osteons (haversian systems) surrounding a central canal, and volkmann canals, which radiate from the central canal connecting neighboring osteons to form an anatomizing network for blood and lymph. 20% is trabeculae bone (spongy) (vertebra, the ends of long bones and flat bones.) In trabeculae bone, lamellas are arranged in longitudinal bundles and anastomose with the marrow cavity. Please note that the surface area of trabeculae bone is 5 times that of compact bone.

Bone formation is controlled by osteoblast differentiation, proliferation, matrix formation and mineralization (by alkaline phosphatase cleaving phosphate groups.)

Bone contains many growth factors such as:

• Transforming growth factor B produced by the osteoblasts, which stimulate mitogenesis and collagen synthesis

• IGF 1 and IGF 2

Bone proteins consist of 13 forms of collagen, osteonectin (a carbohydrate containing protein), osteocalcin, osteopontin (produced by osteoblasts) and proteoglycans (glycosaminoglycans), which are controlled by autocrine, paracrine and systemic hormone regulation. Osteocalcin is a protein making up 1-2% of the total bone protein and depends on vitamins D, K, and C.

PROMOTERS OF BONE FORMATION

• INSULIN

• IGF 1 and 2

• ESTROGENS/ANDROGENS

• GROWTH HORMONE

• THYROID HORMONE

• PTH

PROMOTERS OF BONE REABSORPTION

• PTH

• Interleukin 1

• Prostaglandins

• Thyroid hormone

• Epidermal growth factor

• Vitamin A

• Tumor necrosing factor

INHIBITS BONE REABSORPTION

• Calcitonin

• Phosphate

• Glucocorticoids

FORMATION OF THE CALCIFEROLS

7-DEHYDRO CHOLESTEROL OR ERGOSTEROL

PLUS LIGHT

LUMSTEROL PREVITAMIN D TACHYSTEROL

VITAMIN D2 D3

(CHOLECALCIFEROL) (ERGOCALCIFEROL)

DIHYDROTACHYSTEROL

D3 is formed through irradiation of 7 dehydrocholesterol. Dihydroxycholecalciferol lines the intestinal epithelium, absorbing large quantities of calcium when needed in the blood or bone. On the other hand, phosphorus is easily absorbed, unless there are large quantities of calcium that combine with phosphate creating an insoluble calcium phosphate compound that is excreted from the bowel. Ninety percent of all calcium loss is from the bowel. Ten percent is excreted in the urine. The ten percent that is excreted in the urine is controlled by parathyroid hormone, which also causes the excretion of phosphorus.

Plasma calcium is found in three different forms:

• 40% is combined with plasma proteins

• 10% is bound to phosphates and is not usable

• 50% is in the ionized and diffusible state necessary for heart function, bone formation, and nervous system control.

Phosphates exist in two states HPO4, HPO4. When the pH of the extracellular fluid becomes acid, there is an increase in HPO4 and a decrease in HPO4, with the reverse also being true. Phosphorus levels can dramatically change without affecting function. On the other hand, increased amounts of calcium in the blood can cause central nervous system depression. Decreased calcium in the blood can lead to tetney.

Parathormone controls calcium ion concentration in the extracellular fluid by controlling calcium absorption in the intestines, excretion via the kidneys (increases distal tubular reabsorption of calcium and magnesium) and release of calcium from the bones.

Magnesium can exert control over PTH retention.

Calcitonin (CT) is secreted by the parafollicular cells of the thyroid gland as mentioned above, has the opposite effect of parathormone. Although the effect is much weaker than parathormone, there is still that balance necessary to be maintained.

Calcium also stimulates the secretion of CT, as does beta androgenic catecholamines, gastrin, and cholecystokinin. CT decreases alkaline phosphatase, pyrophosphatase activity, and hydroxyproline production. CT inhibits calcium reabsorption from bone.

Therefore parathormone, which is a polypeptide (110 amino acids long), together with calcitonin (32 amino acid’s long), regulates the calcium-phosphorus ratio. If you lack calcium/phosphorus in the blood, then parathormone will shift them out of the bone and decrease excretion from the distal kidney tubules.

Bone is composed of:

• 90-95% collagen (protein)

• 5% ground substance, which is composed of fluid, proteoglycans, chondroitin sulfate and hyaluronic acid.

• 5% bone salts composed of calcium and phosphorus. The major crystalline salt is hydroxyapatite (CA10 (PO4) 6 (OH) 2), along with other bone salts such as magnesium, sodium, carbonate, uranium, plutonium, strontium and K.

PHOSPHORUS AND CALCIUM INVOLVEMENT IN DIGESTION

Phosphorus is also the regulator of the stomach. Phosphorus regulates the amount of HCl and pepsin in the stomach, which controls carbohydrate metabolism via the process of phosphorylation. Phosphorylation is the process that hydrogenates the carbohydrate, which alters the pH for glycogen storage in the liver. Oxygen, on the other hand, oxidizes carbohydrates for immediate use.

The thymus, which will be covered later, assists the parathyroids in the process of phosphorylation. If the phosphorus in the stomach is too low, then the carbohydrate cannot be hydrogenated and the HCl content of the stomach increases, causing an acid stomach. When the phosphorus content is too high, there is a depletion of HCl content in the stomach. This creates an alkaline stomach.

Calcium is the regulator of the small intestines. Calcium, along with B12 and folic acid, attach to lipoproteins so that they can be polarized through the intestinal wall, via magnesium. At the proper time, the calcium will be severed from the lipoprotein when needed for hormone, enzyme, and antibody formation. At that point, the calcium will be released back into the body. The following tests can be used to assess parathyroid function:

1. CALCIUM

2. PHOSPHORUS

THE PANCREAS

The pancreas is composed of a head and a tail. The purpose of the pancreatic head is used to secrete pancreatic enzymes. The purpose of the pancreatic tail is to produce insulin. I will first discuss the pancreatic head.

THE PANCREATIC TAIL

The pancreatic tail (islets of Langerhan) produces the following hormones:

1. Insulin-which has a molecular weight of 5,808, is produced by the beta cells and has the following functions:

a. Inhibits liver phosphorylate for prevention of glycogen breakdown

b. Increases activities of enzymes that promote glycogen synthesis

a. Increases the flow of glucose to the liver

b. Increases sugar flow into fat cells, causing the production of glycerol for fat production with fatty acids

c. Increases membrane permeability for glucose, amino acids, potassium, magnesium, and phosphates

f. Increases translation of messenger RNA and the formation of proteins

g. Decreases the rate of gluconeogenesis in the liver

h. Decreases catabolism of proteins

It is interesting to note that gastrin, secretin, cholecystokinin, somatotrophin, cortisol, glucagon, progesterone and estrogen all affect the release of insulin.

It is also interesting that resting muscles use fatty acids for energy and, when working hard, use glucose for energy.

2. Glucagon-which has a molecular weight of 3,485 and is 29 amino acids long, is produced by the alpha cells and has the following functions:

a. Promotes the breakdown of glycogen in the liver (glucogenesis) by the following process. Glycogen is activated by adenyl cylclase, which is found in the hepatic cell membranes. This forms cAMP (adenosine mono-phosphate), which activates the protein kinase. The protein kinase then activates phosphorylate B kinase, which is converted into phosphorylate A kinase, which causes the degradation of glycogen into glucose 1 phosphate, which is then dephosphorylated into glucose and released into the bloodstream.

b. Promotes gluconeogenesis in the liver

3. Somatostatin-which is 14 amino acids long, produced by delta cells and does the following:

a. Decreases insulin and glucagon secretion

b. Decreased motility, secretions of the stomach and the GI tract

It is interesting that somatostatin is the same chemical substance as somatotrophin inhibiting hormone, which is released by the hypothalamus and suppresses the anterior pituitary from releasing growth hormone.

4. Pancreatic polypeptide secreted by the PP cells and has uncertain functions.

The overall purpose of the pancreatic tail is to regulate muscle tone by balancing sugar and water across the muscle cell interface (membrane.) The pancreas via insulin utilizes zinc as a carrier mechanism to create this effect. As you may recall, actin is the active fiber that is burning and myosin, the stable protein block that contracts and is dramatically affected by this process.

If sugar and water are not balanced accurately, then we have a loss or increased amount of insulin penetration into the cell. This will cause the body great difficulty with sugar metabolism. This may lead to a crystalline blockage, especially at the level of the motor end plate, creating neurological problems. The true pancreatic patient does not have stamina and ages quickly. One of the first complaints of a diabetic is that they sweat a lot and have increased urination, which causes the diabetic to drink a lot of water.

The hypoglycemic, on the other hand, has poor circulation and muscle coordination. The tone of the blood vessels is poor and causes the blood vessel walls to prolapse, allowing blood to pool in the central cavity of the body. The hypoglycemic patient breaks out into cold sweats with spastic trembling to get sugar across the muscle wall. Hypoglycemics also hold fluid, as the kidneys go alkaline which prevents urination.

In order for sugar to be handled properly it must go through the following four processes:

Reaction 1-Copper via the parotids must first tag the carbohydrate. The parathyroids, through the process of “phosphorylation,” add phosphorus to the carbohydrate. So, the first thing that takes place with the preparation of sugar is the phosphorus injecting ability of choline and inositol into the sugar, creating the proper acid-alkaline balance within that sugar for further breakdown. Therefore, the first step in preparing the sugar zinc compound (insulin) occurs in the stomach via pepsin. Chlorine is then added to the compound via HCl acid/pepsin release in the stomach, which is controlled by the adrenal medulla. Once the carbohydrate is properly prepared, it now enters the bloodstream and travels to the liver.

Reaction 2-Once in the liver, the thyroid converts sugar into glycogen by removing nitrogen via iodine. Then glycogen is released by epinephrine and is then activated on by adenyl cylclase that is found in the hepatic cell membranes. This forms cAMP (adenosine mono-phosphate), which activates protein kinase. The protein kinase then activates phosphorylate B kinase, which is converted into phosphorylate A kinase, which causes the degradation of glycogen into glucose 1 phosphate, which is then dephosphorylated into glucose and released into the bloodstream. This only occurs if there are sufficient amounts of zinc and selenium (insulin) outside the liver, which will draw the sugar out of the liver and into the blood.

Zinc is also used to make peptidases for protein digestion and is a component part of LDH via inter-conversion of pyruvic acid into lactic acid. Zinc is also an integral part of carbonic anhydrase, which is found in red blood cells. The purpose of carbonic anhydrase is to adhere to carbon dioxide and water so that it can be expired by the lungs.

Carbonic anhydrase is also found in the gastrointestinal tract and kidneys.

Reaction 3-In order for the insulin/sugar compound to leave the blood and enter the extracellular fluid, glucagon is now necessary for this to occur. When zinc is in higher quantities in the extracellular fluid, in combination with selenium, they draw sugar out of the blood and into the extracellular fluid. The uterus and prostate control selenium. This will be discussed later.

Reaction 4-When the sugar/insulin compound reaches the cell membrane, the selenium draws the sugar into the membrane. At this point, there is a selenium and potassium regulator known as oxytocin, which is released by the posterior pituitary (and closely resembles antidiuretic hormone), which holds the sugar for storage in the cell membrane. This membrane oxytocin is the regulator at every cell membrane for sugar and water entry into the cell to be metabolized. The oxytocin now causes the internal potassium to oxidize the chloride, shifting chloride out of the way, allowing the sugar and water to pass into the cell, which is then combusted to form lactic acid and converted back into lactic acid dehydrogenase in the veins.

The following blood tests determine pancreatic tail function:

1. PHOSPHORUS-indicates the amount of acid balance in the body. It does this via regulating secretions of HCl/pepsin ratios in the stomach. For example, if the food you eat contains large amounts of phosphoric acid, pepsin will be released to neutralize the acid. If the food contains very little phosphoric acid, large amounts of HCl will be released. Phosphoric acid, as explained before, creates the proper balance of choline and inositol into the sugar, affecting sugar metabolism from this point forward. Increases in blood acidity may be due to an increase of zinc and sugar. Alkaline blood is due to a decrease of zinc and sugar. The pancreatic tail regulates this acidity/alkalinity via insulin/glucagon.

2. LACTIC ACID DEHYDROGENASE-is a byproduct of sugar metabolism, as mentioned above. Lactic acid dehydrogenase (LDH) is a glycolytic enzyme that functions as a catalyst in carbohydrate metabolism, which aids the pyruvic and lactic acid interchange. LDH is a byproduct of muscle metabolism. When sugar and water (fatty acid metabolism) are exchanged across a muscle cell interface, a byproduct known as lactic acid is produced. Lactic acid is a byproduct of fatty acid metabolism via the alkalizing and oxidizing effect of the pancreatic head. When lactic acid combines with the venous blood (carbon dioxide), there is a hydrogen displacement. Lactic acid then bonds to a double hydrogen, forming lactic acid dehydrogenase. The organs and glands most responsible for the sugar and water interchange across a muscle cell interface are the pancreas and posterior pituitary (via antidiuretic hormone.)

LDH is chiefly found in the heart, kidneys, liver, skeletal muscle, as well as all tissues. LDH is a normal component of the cerebral spinal fluid.

THE PITUITARY GLAND

The pituitary, the existence of which has been known for 2000 years, sits in the sella turcica of the sphenoid bone. The sella turcica forms the roof of the sphenoid sinus. The lateral walls are comprised of durra or bone, which abut the cavernous sinuses and can affect the 3rd, 4th, and 6th cranial nerves and the internal carotid arteries since they transverse thru this area.

The cavernous sinuses can exert a great deal of CSF pressure but, due to the diaphragm sellae, the gland will not become compressed nor will the optic chiasm and tracts, which lie immediately above the diaphragm sellae. Also lying in close proximity to the cavernous sinuses are the internal carotid arteries, cranial nerves 3, 4, 5 and 6, the third ventricle and the optic chiasm, which lies above the diaphragm sellae.

The pituitary is divided into three parts:

1. ADENOHYPOPHYSIS-is the anterior portion, which is derived from Rathke’s pouch. This is divided into three lobes: the pars distalis (anterior lobe,) the pars intermedia (intermediate lobe) and the pars tuberalis.

2. NEUROHYPOPHYSIS-is the posterior portion and is composed of the pars nervosa, the infundibular stalk, and the median eminence. The major supply of axons to the neural lobe is the magnocellular secretory neurons from the paraventricular and supraoptic nuclei of the hypothalamus. These axon terminals also secrete AVP (regulating blood osmolarity, pressure, and fluid balance) and oxytocin into the surrounding capillary beds leading into the hypophyseal veins. The infundibular stalk is surrounded by the pars tuberalis, and together they make up the hypophyseal stalk.

3. VESTIGIAL INTERMEDIATE LOBE

.

The pituitary gland is regulated by the hypothalamus via feedback mechanisms of hormones and from paracrine and autocrine secretions from the pituitary itself. It attaches to the hypothalamus via the stalk thru the diaphragm sellae and into the median eminence.

The pituitary is derived from the:

• ECTODERM-which forms the pars distalis/tuberalis and the intermediate lobe

• NEURAL PORTION-which forms the infundibulum, posterior pituitary, and neural stalk

The pituitary weighs between 4-900 mgs (during pregnancy up to 1 gram), is bean shaped and brownish in color with dimensions of 9 mm A/P, 6mm S/I, 13 mm laterally. The hypothalamus receives its blood supply from the superior (provides 10-20 % of the blood supply) and inferior hypophyseal arteries (supply blood to the posterior pituitary), which are derived from the internal carotid arteries. These arteries form a capillary network in the median eminence (external to the blood-brain barrier).

This capillary network picks up hypothalamic secretions from the hypothalamic nerve endings delivering them into the long and short hypophyseal portal veins, which are now transported to the anterior pituitary. Please note that retrograde blood flow causes bi-directional movement of blood between the hypothalamus and pituitary. Once the hypothalamic releasing hormones reach the pituitary, they activate G protein receptors on the cell membrane, creating a cascading chain reaction for the production of their pituitary hormone counterparts. Blood drainage of the pituitary leaves through the cavernous sinuses and the petrosal veins and out the jugular foramina via the jugular vein. Note that the blood supply to the pituitary via the hypothalamus is not unidirectional and can flow both ways creating ultra-short biofeedback loops.

The hypothalamus releases its secretions via hypothalamic neurons, which end in the infundibulum and permeate into the fenestrations at the perigomitolar capillaries. This enters the portal vein, which enters the capillary circulation of the anterior pituitary (which provides 80-90 % of the blood supply to the pituitary). The pituitary, as stated above, is attached to the hypothalamus via the pituitary infundibulum.

The diaphragm sellae has a 5mm opening for the hypophyseal stalk and allows transmission of pulsations of CSF. The purpose of the pituitary infundibulum is to act as a direct pathway for hormonal secretion between the hypothalamus and the pituitary. Pituitary hormones are released as pulsations, which does affect hormonal levels minute, by minute, which may give false positives when measuring hormonal levels.

Each releasing factor (hormone) that is released from the hypothalamus causes a release of a hormone from the anterior pituitary. The hypothalamus also produces two hormones called antidiuretic hormone and oxytocin. Anti-diuretic hormone is formed primarily by the supraoptic nuclei, whereas oxytocin is formed primarily in the paraventricular nuclei. The major nerve tracts of the neurohypophysis arise from these two nuclei, from large cells termed magnocellular cells forming the supra optico hypophyseal tract and the paraventricular hypophyseal tract. AVP and oxytocin tracts are also distributed widely and project into the brain stem affecting the vagal nuclei, glossopharyngeal nuclei, and the spinal cord, sending information to the ANS to evaluate blood pressure. Vasopressinergic and oxytocin fiber pathways (which have different effects than those that end in the posterior pituitary) also terminate in the choroid plexus, which influences salt and water exchange between the brain (especially regions associated with emotion and memory) and the CSF.

Neurological impulses from the two nuclei above, cause secretory granular release of these two hormones into the posterior pituitary, which are then released into the adjacent capillaries. It is interesting to note that the differences between oxytocin and anti-diuretic hormone are two amino acids. Otherwise, the chains are identical. The functions are entirely different, as you will see.

The anterior pituitary is controlled by the hypothalamus in a slightly different manner than the posterior pituitary. Oxytocin and anti-diuretic hormone (AVP) are produced in the hypothalamus and are released into the posterior pituitary, via the neurological tracts of those nuclei mentioned above in the hypothalamus. Other neurological tracts secrete other neuropeptides called TRH (thyrotrophin releasing factor), CRH (corticotrophin releasing hormone), VIP and neurotensin. Paraventricular hypophyseal tracts located on either side of the ventricles are both unmylenated and descend thru the infundibulum. The releasing factors from the hypothalamus are transmitted to nerve endings, which then release these factors into a primary plexus of veins known as the hypophyseal portal system. These veins are located in the pituitary infundibulum and travel into the anterior pituitary, releasing the hypothalmic hormones into and stimulating the anterior pituitary.

THE POSTERIOR PITUITARY

(NEUROHYPOPHYSIS, INFUNDIBULAR PROCESS)

The posterior pituitary includes the pars nervosa, infundibular stalk, and the median eminence, and is directly innervated by the supraoptic hypophyseal and the tuber hypophyseal neurological tracts. The median eminence, which lies in the tuber cinereum, has an internal zone from which the supraoptic and paraventricular magna cellular neurons control the posterior pituitary and an external zone, which receives information from the hypophyseal trophic neurons (sensory trophic neurons.) The magnocellular neurons embrionically arise out of neuroepithelial cells lining the third ventricle, which form the supraoptic nuclei above the optic chiasm, and the paraventricular nucleus located in the third ventricle.

A third structure, which is also considered part of the median eminence, is the pars tuberalis, which surrounds the infundibulum and pituitary stalk. The median eminence is composed of nerve endings and blood vessels and is truly the functional link between the hypothalamus and the pituitary. The median eminence receives blood supply from the posterior communicating and superior hypophyseal artery (from the internal carotid) and drains thru the cavernous sinuses.

The blood then flows thru capillary loops, which anastomose and drain into the sinusoids, which become the pituitary portal veins. The pituitary portal veins drain into the pituitary, the neural stalk and specialized neuro tissues that lie at the base of the hypothalmic pituitary juncture. This forms the base of the third ventricle, creating a funnel (infundibulum), and literally draining into the CSF as well as releasing neurosecretions into the anterior pituitary.

The 2 major hypothalamic/posterior pituitary nerve tracts, which arise from magnicellular cells, are the bilateral supraoptic nucleus and the paraventricular nucleus and they produce (via ribosome protein synthesis) a pre-prohormone. Then, via glycosylation in the Golgi apparatus, the pre-prohormone is made into the prohormone and transported via neurosecretory granules (inactive state), where the secretory granular membrane adheres to the plasma membrane, releasing the granular material into the cell. It is then stored in the posterior pituitary as a neurophysin.

Then, through the process of exocytosis, anti-diuretic hormone (AVP) and neurophysin 2 are released via neuron bombardment into the blood stream. There are two receptor sites: V1 found in smooth muscle, and V2 found in renal epithelial. V2 activates antidiuretic activity by activation of adenylate cylclase.

Once the neurophysin is cleaved, the hormones are released. Capillaries and glue like non-secretory cells (pituicytes) help bind together the posterior pituitary. The capillaries are different in that they allow diffusion of the neurosecretory cells into the blood stream, unlike other capillaries in the brain that are subject to the blood brain barrier, preventing diffusion into circulation. The purpose of the posterior pituitary is to regulate body cell osmolarity by regulating sodium concentration, and by effective extracellular fluid regulation via osmoreceptors.

Osmoreceptors for thirst and AVP release respond to slight changes in extracellular fluid osmolarity. The primary osmoreceptors that are triggered are triggered by urea and glucose for sensing changes in osmolarity and are found in the brain and outside the blood brain barrier. For example, an increase in ECF (extracellular fluid) osmolarity causes shrinkage of the cells, stimulating the osmoreceptors inside the cells to stimulate the release of AVP and angiotensin 2, conserving H20. Bar receptors are of two types:

• Low pressure found in the right side and left atrium of the heart

• High pressure found in the carotid sinus and aortic arch. This stimulates the vagus nerve and the glossly pharyngeal to the nucleus tractus solitarius then via noradrengic projections into the PVN and SON, which then inhibits the release of AVP

To a lesser degree, a drop in blood volume stimulates angiotensin 2 and AVP release, stimulating thirst and increasing blood volume. Once blood volume is up, the oropharyngeal reflex and the release of atrial natriuretic peptide suppresses thirst. In actuality, the purpose then becomes regulating cell volume against extracellular fluid. The goal is to create a balance in Intra and extracellular osmolarity, whereby permeability would be perfect for passive and active transport (keeping the highways open between the cells and the extracellular fluids they bathe in.) This allows cell metabolites, CO2, hormones, enzymes and antibodies to diffuse with ease out of the cell while letting food, enzymes, hormones and oxygen to enter the cell.

From an active standpoint, sodium constantly leaks into the cell, and potassium leaks out of the cell. This is due to their respective concentration gradients. Via active transport, the sodium-potassium ATPase extrudes the sodium to outside the membrane, and at the same time potassium is pulled back in. As potassium is leaking out via passive diffusion, it is being pulled back in via active transport.

The following hormones, which are octal peptides with similar structural formulas, are released from the posterior pituitary:

1. ANTI-DIURETIC HORMONE (AKA VASOPRESSIN, ARGININE VASOPRESSIN, AVP) and its related neurophysin one (propressophysin, prohormone) cause the kidneys to retain water, excrete sodium while retaining potassium, and raising blood pressure through vasoconstriction. The most important factor regulating vasopressin is blood osmolarity and circulating blood volume. Increases in osmolarity and decreases in volume both increase vasopressin release. Blood osmolarity is kept within a fine range +- 1.8% of 282 mmo/kg. Other factors that affect blood osmolarity include emotional stress, nausea and blood pressure.

1) Aldosterone has the opposite effect, as well as constricting blood vessels and elevating blood pressure.

The glucocorticoids and mineral corticoids, released by the adrenal cortex, counteract the function of antidiuretic hormone.

Since glucocorticoids control sugar levels in the body, you can see how diabetes insipidus can occur. AVP release is also enhanced by prostaglandin E 2, morphine, nicotine, acetylcholine, histamine, barbiturates and hypoxia. Other factors that suppress AVP are alcohol and atrial natriuretic peptide.

DIABETES INSIPIDUS

This is a condition where there is a large volume of urine that is dilute (hypotonic) and tasteless (insipidus.) In diabetes mellitus, the urine is hypertonic and sweet tasting like honey (mellitus.)

1. OXYTOCIN AND ITS RELATED NEUROPHYSIN 2 (PROOXYPHYSIN) causes contraction of the uterus during the birth process and causes the contraction of the myo-epithelial cells in the breasts when the baby suckles. Oxytocin is also involved in maintaining the uterus in a quiet state during pregnancy. Oxytocin is also responsible for maternal behavior. Oxytocin is found in the ovary, placenta, testis, renal medulla, thymus and anterior pituitary. Oxytocin may also affect feeding behavior, gonadotrophin secretion, response to stress (decreasing stress), stimulation of the tubules in the spermatic ducts, regulating blood pressure, temperature, and heart rate. Just like AVP, oxytocin release is stimulated by plasma hypertonicity and suppressed by plasma hypotonicity via binding to high-affinity receptors. It stimulates cAMP, which increases natriferic and hydro-osmotic responses of the tissue.

4. 4. The posterior pituitary and the adrenal glands regulate mineral, water and sugar levels in the body. Factors that stimulate oxytocin secretion are nausea, saity, cholecystokinin and angiotensin 2. Factors that inhibit oxytocin are opiods, relaxing and ANP.

Both oxytocin and AVP and their related neurophysin are synthesized in both the supra-optical (most oxytocinergic) (dorsal portion) and vasopressin (ventral portion), which project into the posterior pituitary and via the paraventricular nucleus, which is divided into 3 distinct magno cellular divisions consisting of:

• Oxytocinergic neurons

• Vasopressin neurons

• Par cellular division that synthesizes peptides, corticotrophin releasing hormone, thyrotrophin releasing hormone, somatostatin, and opiods. Projections from pare cellular neurons project into the median eminence, brain stem and the spinal cord for autonomic function. The supra chiasmic nucleus in the third ventricle secretes only vasopressin and controls circadian and seasonal rhythms. Ventricular neurons triggered by nerve action potentials, via cholinergic and noradrenergic neurotransmitters, and several other neuropeptides including angiotension 2, atrial peptide (AP), and atrial natriuretic factor (ANF) cause an influx of calcium. This induces movement of the neuro secretory granules to the membrane surface, causing a release of the hormones from the granules into per vascular space. From there, it enters into the capillary system of the posterior pituitary, or via microtubule tracts. Acetylcholine stimulates AVP via nicotinic acid receptor stimulation and oxytocin release where adrenergic influences inhibit oxytocin and AVP secretion thru beta androgenic receptors. They are then transported via vesicles into the axons to the neural lobe. Both hormones and their neurophysins are released in fixed ratios.

Other substances released from the posterior pituitary include:

• Somatostatin

• SRIF (somatotrophin release inhibiting factor)

• TRH

• Substance P

• LHRH

• GNRH (gonadotrophin- releasing hormone)

• Dopamine

• Serotonin

• Histamine

• Beta-melanocyte-stimulating hormone (b-MSH)

• An opium peptide named dynorphin a 1-8, which is present in AVP-containing neurons

From a biochemical perspective, the posterior pituitary controls biochemistry by maintaining potassium levels in all cells. As you may already be aware, potassium levels are highest within the cell. The purpose of potassium within cells is to maintain water levels. Potassium has been coined the “oxidative life principle” of the body. If this balance is affected, cells can either burst or shrink.

In so doing, potassium literally pulls foodstuffs (that are stored in the cell membrane) through the membrane of the cell and into the mitochondria for energy. Now, via the demand of the cell, the potassium, which is controlled by the posterior pituitary, donates oxygen to this hydrogenated foodstuff on the membrane and draws it into the cell. When the pressure gradient of potassium becomes too high on the inside of the cell, potassium, along with metabolic waste products, is transported out of the cell. Therefore, by balancing water levels in body, the posterior pituitary can balance the body’s pH.

The posterior pituitary also balances the pH of the body by affecting sugar levels (which are acids) and minerals (which are alkaline). So, in essence, the posterior pituitary, the pancreas, and adrenals dramatically affect the above.

The following blood tests assess the functions of the posterior pituitary:

1. POTASSIUM as mentioned above is the primary indicator for posterior pituitary function.

2. TRIGLYCERIDES are composed of a molecule of glycerol and three molecules of fatty acids. The energy necessary for active transport across a cell membrane, via the influence of potassium, is supplied by fatty acids.

3. GLUCOSE although affected by many other organs and glands, glucose is also affected by the posterior pituitary.

4. BUN/CREATININE RATIO blood urea nitrogen and creatinine are residue byproducts found at the end of protein and muscle metabolism. They are kept in continual balance via the water content in our body. The kidneys flush out the blood urea nitrogen and creatinine when the concentrations get too high, via antidiuretic hormone release from the posterior pituitary.

THE PITUITARY GLAND

The pituitary, the existence of which has been known for 2000 years, sits in the sella turcica of the sphenoid bone. The sella turcica forms the roof of the sphenoid sinus. The lateral walls are comprised of durra or bone, which abut the cavernous sinuses and can affect the 3rd, 4th, and 6th cranial nerves and the internal carotid arteries since they transverse thru this area.

The cavernous sinuses can exert a great deal of CSF pressure but, due to the diaphragm sellae, the gland will not become compressed nor will the optic chiasm and tracts, which lie immediately above the diaphragm sellae. Also lying in close proximity to the cavernous sinuses are the internal carotid arteries, cranial nerves 3, 4, 5 and 6, the third ventricle and the optic chiasm, which lies above the diaphragm sellae.

The pituitary is divided into three parts:

1. ADENOHYPOPHYSIS-is the anterior portion, which is derived from Rathke’s pouch. This is divided into three lobes: the pars distalis (anterior lobe,) the pars inter-media (intermediate lobe) and the pars tuberalis.

2. NEUROHYPOPHYSIS-is the posterior portion and is composed of the pars nervosa, the infundibular stalk, and the median eminence. The major supply of axons to the neural lobe is the magnicellular secretory neurons from the paraventricular and supraoptic nuclei of the hypothalamus. These axon terminals also secrete AVP (regulating blood osmolarity, pressure, and fluid balance) and oxytocin into the surrounding capillary beds leading into the hypophyseal veins. The infundibular stalk is surrounded by the pars tuberalis, and together they make up the hypophyseal stalk.

3. VESTIGIAL INTERMEDIATE LOBE

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The pituitary gland is regulated by the hypothalamus via feedback mechanisms of hormones and from paracrine and autocrine secretions from the pituitary itself. It attaches to the hypothalamus via the stalk thru the diaphragm sellae and into the median eminence.

The pituitary is derived from the:

• ECTODERM-which forms the pars distalis/tuberalis and the intermediate lobe

• NEURAL PORTION-which forms the infundibulum, posterior pituitary, and neural stalk

The pituitary weighs between 4-900 mgs (during pregnancy up to 1 gram), is bean shaped and brownish in color with dimensions of 9 mm A/P, 6mm S/I, 13 mm laterally. The hypothalamus receives its blood supply from the superior (provides 10-20 % of the blood supply) and inferior hypophyseal arteries (supply blood to the posterior pituitary), which are derived from the internal carotid arteries. These arteries form a capillary network in the median eminence (external to the blood-brain barrier).

This capillary network picks up hypothalamic secretions from the hypothalamic nerve endings delivering them into the long and short hypophyseal portal veins, which are now transported to the anterior pituitary. Please note that retrograde blood flow causes bi-directional movement of blood between the hypothalamus and pituitary. Once the hypothalamic releasing hormones reach the pituitary, they activate G protein receptors on the cell membrane, creating a cascading chain reaction for the production of their pituitary hormone counterparts. Blood drainage of the pituitary leaves through the cavernous sinuses and the petrosal veins and out the jugular foramina via the jugular vein. Note that the blood supply to the pituitary via the hypothalamus is not unidirectional and can flow both ways creating ultra-short biofeedback loops.

The hypothalamus releases its secretions via hypothalamic neurons, which end in the infundibulum and permeate into the fenestrations at the perigomitolar capillaries. This enters the portal vein, which enters the capillary circulation of the anterior pituitary (which provides 80-90 % of the blood supply to the pituitary). The pituitary, as stated above, is attached to the hypothalamus via the pituitary infundibulum.

The diaphragm sellae has a 5mm opening for the hypophyseal stalk and allows transmission of pulsations of CSF. The purpose of the pituitary infundibulum is to act as a direct pathway for hormonal secretion between the hypothalamus and the pituitary. Pituitary hormones are released as pulsations, which does affect hormonal levels minute, by minute, which may give false positives when measuring hormonal levels.

Each releasing factor (hormone) that is released from the hypothalamus causes a release of a hormone from the anterior pituitary. The hypothalamus also produces two hormones called anti-diuretic hormone and oxytocin. The anti-diuretic hormone is formed primarily by the supraoptic nuclei, whereas oxytocin is formed primarily in the paraventricular nuclei. The major nerve tracts of the neurohypophysis arise from these two nuclei, from large cells termed magnocellular cells forming the supra optico hypophyseal tract and the paraventricular hypophyseal tract. AVP and oxytocin tracts are also distributed widely and project into the brain stem affecting the vagal nuclei, glossopharyngeal nuclei, and the spinal cord, sending information to the ANS to evaluate blood pressure. Vasopressinergic and oxytocin fiber pathways (which have different effects than those that end in the posterior pituitary) also terminate in the choroid plexus, which influences salt and water exchange between the brain (especially regions associated with emotion and memory) and the CSF.

Neurological impulses from the two nuclei above, cause a secretory granular release of these two hormones into the posterior pituitary, which are then released into the adjacent capillaries. It is interesting to note that the differences between oxytocin and anti-diuretic hormone are two amino acids. Otherwise, the chains are identical. The functions are entirely different, as you will see.

The anterior pituitary is controlled by the hypothalamus in a slightly different manner than the posterior pituitary. Oxytocin and anti-diuretic hormone (AVP) are produced in the hypothalamus and are released into the posterior pituitary, via the neurological tracts of those nuclei mentioned above in the hypothalamus. Other neurological tracts secrete other neuropeptides called TRH (thyrotrophin releasing factor), CRH (corticotrophin releasing hormone), VIP and neurotensin. Paraventricular hypophyseal tracts located on either side of the ventricles are both unmylenated and descend thru the infundibulum. The releasing factors from the hypothalamus are transmitted to nerve endings, which then release these factors into a primary plexus of veins known as the hypophyseal portal system. These veins are located in the pituitary infundibulum and travel into the anterior pituitary, releasing the hypothalmic hormones into and stimulating the anterior pituitary.

THE ANTERIOR PITUITARY

(PARS DISTALIS, PARS GLANDULARIS)

The anterior lobe is composed of 3 divisions:

1. PARS DISTALIS – largest and produces most of the hormones

2. THE INTERMEDIA-the least developed

3. TUBERALIS-attached to the pituitary stalk and produces many of the glycoproteins. At this poin, there are cells that produce specific hormones, from specific releasing factors released from specific areas in the hypothalamus. There are 5 specific secreting cells that arise from totipotential pituitary stem cells of the anterior pituitary. They are:

• CORTICOTROPHIC CELLS-which express POMC (pro-opiomelanocortin) peptides including ACTH

• SOMATOTROPH CELLS-which express growth hormone

• THYROTROPHS-which express TSH

• GONADOTROPHS-which express FSH and LH

• LACTOTROPH CELLS-which produce prolactin

These hormones are produced in the anterior pituitary and are now released into the hypophyseal portal veins. They continue down through the circulatory system to target sites in the body. Any hormones that are now released from the target sites reenter the bloodstream and are transported back to the hypothalamus via the hypothalamic artery and to the pituitary via the hypophyseal artery. This is why it should be looked at as a “neuroendocrine axis” due to this dual control mechanism. It makes much more sense and is more reliable to have each system checking and balancing each other.

The following hormones are released from the anterior pituitary:

1. FOLLICLE STIMULATING HORMONE (GONADOTROPHINS) -are released by lutenizing hormone-releasing hormone (LHRH) via the hypothalamus. Gonadotrophin cells make up 10-15 % of the anterior pituitary. FSH and LH regulate gonadal steroid hormone biosynthesis and germ cell production. FSH, LH, TSH, and HCG are all glycoproteins. The purpose of follicle stimulating hormone is to stimulate the growth of the follicle on the ovary. FSH, LH, TSH AND HCG all have identical alpha subunit chains. These are polypeptides containing 92 amino acids, whereas the beta subunit chains contain 117, 121, and 145 amino acids. LHRH synthesizes these alpha and beta gonadotrophin subunits forming and secreting FSH, LH, CRH (corticotrophin releasing hormone) and progesterone.

The follicle-stimulating hormone increases estrogen levels. As estrogen levels rise in the bloodstream, they enter the hypothalamic artery and decrease the output of LHRH from the hypothalamus. There are also a group of peptide hormones produced by the gonads called inhibins, which are produced by the follicular-luteal and sertoli cells of the gonads that inhibit FSH secretion, without affecting LH secretion. Activins also produced by the above cells stimulate GnRF, which induces FSH production. Activins and inhibins regulate granulose cell growth, differentiation, steroid hormone production, oocyte maturation and follicular development.

You will notice that most hormones either increase or decrease the output of other hormones through this kind of a feedback mechanism. If a hormone increases the output of another hormone, then it is said to be a positive feedback mechanism. On the other hand, if a hormone decreases the output of another hormone, then it is said to be a negative feedback mechanism.