1. The Digestive System-Chapters 62-66; 70; 78
Well come to your articulate file for the Digestive system –or alimentary tract. The alimentary tract begins with the oral cavity, continues into the oropharynx and laryngopharynx to the esophagus, to the stomach, to the small intestine with its three parts (duodenum, jejunum, and ileum—I remember this as “Down Jones Industrial” finally the ingested contents travel through the one-way ileocecal valve and enter the large intestine leading to the rectum and anus. Many accessory digestive organs are passed along the way: such as the pancreas, liver, and gallbladder.
The alimentary tract provides the body with continual supply of water, electrolytes, and nutrients. This requires (1) movement of food through the alimentary tract; (2) secretion of digestive juices and digestion of food; (3) absorption of digestive products, water, and various electrolytes; (4) circulation of blood to carry away absorbed substances; and (5) nervous and hormonal control of all these functions. I will be discussing the basic principles and function of the entire alimentary tract during this lecture
Figure 62-1; Guyton & Hall

2. Digestive Processes Ingestion Propulsion
Digestion: Mechanical and Chemical digestion
Absorption- nutrients and water
Defecation
For food to be processed optimally in the alimentary tract, the length of time it remains in each part of the tract is critical, and appropriate mixing must occur. First lets cover the ingestion of food: When food is ready for swallowing, it is voluntarily pushed into the pharynx by the tongue. The food is now propelled forward into the other portions of the alimentary tract through involuntary mechanisms. The upper esophageal sphincter relaxes and this allows food to pass from the pharynx to the upper esophagus. A fast peristaltic wave originating in the pharynx forces the bolus of food into the upper esophagus. What is peristalsis? Peristalsis is the basic propulsive movement of the gastrointestinal tract. It occurs because distention of the digestive tract causes a reflexive contractile ring to appear around the gut (remember that with smooth muscle more stretch causes contraction) and this contractile ring moves forward a few centimeters before ending and therefore propels the food bolus forward. At the same time, the gut sometimes relaxes several centimeters down toward the anus, which is called receptive relaxation, allowing the food to be propelled more easily toward the anus. This complex pattern does not occur in the abscence of the myenteric plexus (which I will describe soon); therefore, the complex is called the myenteric reflex, or peristaltic reflex. The peristaltic reflex plus the direction of movement toward the anus is called the “law of the gut,” or as I like to say, food in- food out. Children obey the law of the gut quite well: you can bet money on their regularity. 20 minutes after they eat, they have to poop. Once the bolus of food is in the stomach and intestines digestion can occur. Digestion occurs through mechanical and chemical means. First mechanical. Our mouth begins mechanical and chemical break down of food through chewing and secretion of saliva. But, this is not the only place in our body where mechanical and chemical breakdown occurs. In fact, the stomach and intestines also provide mechanical breakdown of food through churning in the stomach and segmentation of the intestines. Segmentation occurs when some areas of the intestine have local constrictive contractions that occur every few centimeters in the gut wall. These constrictions last for only a few seconds; then new constrictions occur at other points in the gut, “chopping” the contents first here and then there. The chemical digestion of our food will be discussed later as will the processes of absorption of the nutrients and water. Finally, any ingested material that is not absorbed is defecated out of the body. “Mass movements” are important for propelling the fecal contents through the large intestine. A “Mass movement” is characterized by the following sequence of events: A constrictive ring occurs at the distended point in the colon, and then the colon distal to the constriction contracts as a unit, forcing the fecal material in this segment en masse down the colon. When they have forced a mass of feces into the rectum, the desire for defecation is felt. These “mass peristalsis movments” are reflexes that result from distention of the stomach and duodenum (again- food in—food out). When feces enter the rectum, distention of the rectal wall initiates afferent signals that spread through the myenteric plexus to initiate peristaltic waves in the descending colon, sigmoid, and rectum, forcing feces towardt he anus. As the peristaltic wave approaches the anus, the internal anal sphincter is relaxed by inhibitory signals from the myenteric plexus; if the external anal sphincter is consciously relaxed a the same time, defecation occurs. To be effective in causing defecation, the reflex usually must be fortified by a parasympathetic defecation reflex that involves the sacral segments of the spinal cord (S2-S4). Parasympathetic signals greatly intensify the peristaltic waves, relax the internal anal sphincter, and thus convert the intrrinsic defecation reflex from a weak movement into a powerful process of defecation.

3. Layers Alimentary Canal
1. Serosa
2. Longitudinal muscle (muscularis externa)
3. Myenteric (Auerbach’s) nerve plexus
4. Circular muscle
5. Submucosa
6. Submucosal (Meissner’s) nerve plexus
7. Muscularis mucosae
8. Mucosa
9. Epithelial lining
Before we move on with the physiology of the alimentary canal, let’s review the histology of it. The innermost layer is the mucosa, or mucous membrane. The typical digestive mucosa contains three sublayers shown here in the circle: a lining of columnar epithelium, a lamina propria and a muscularis mucosae. The epithelium is continuous with the ducts and secretory cells of the various digestive glands called intrinsic glands. The lamina propria is a loose areolar or reticular connective tissue whose capillaries nourish the epithelium and absorb digested nutrients. The lamina propria contains most of the mucosa-associated lymphoid tissue (MALT) which defends against invasion by bacteria and other microorganisms in the alimentary canal. External to the lamina propria is the muscularis mucosae, a thin layer of smooth muscle that produces local movements of the mucosa. It is not thick enough to propel food, rather it dislodges sharp food particles that become embedded in the mucosa.

4. Autonomic nerve fibers
Both divisions found in myenteric and submucosal nerve plexi—What do they do?
Sensory neurons that monitor tension, and efferent visceral motor fibers. OWN SYSTEM!
Myenteric-GI motility control
Stimulatory influences -
 tonic contraction (tone)
 contraction frequency / intensity ( propulsion)
Inhibitory influences
Decreased Sphincter tone (relax) - pyloric sphincter, ileocecal sphincter, LES
Submucosal- Local control
Secretion
Absorption
Contraction of muscularis mucosa
The gastrointestinal tract has its own nervous system called the enteric nervous system. It lies entirely in the wall of the gut, beginning in the esophagus and extending all the way to the anus. It is composed of two plexuses, the myenteric and submucosal plexus. I want you to understand that the enteric nervous system is its own system of nerves; it has its own sensory neurons and visceral motor fibers and as such, there are gastrointestinal reflexes that don’t require the central nervous system. These enteric reflexes control gastrointestinal secretion, peristalsis, segmentation, just to name a few. The myenteric plexus, or Auerbach’s plexus is an outer plexus located between the muscle layers. Stimulation causes increased tone of the gut wall, increased intensity of rhythmical contractions, increased rate of contraction, and increased velocity of conduction. The myenteric plexus is also useful for inhibiting the pyloric sphincter and ileocecal valve.
The submucosal, or Meissner’s plexus, is an inner plexus that lies in the submucosa. It is mainly concerned with controlling function in the inner wall of each minute segment of the intestine for local control of intestinal secretion, absorption, and contraction of the submucosal muscle.
There are parasympathetic and sympathetic fibers that synapse with the enteric nervous system that can modify the activity of the enteric nerves. Yet again, the emphasis is on the word “modify” as the enteric nervous system controls most of its own activity.

5. Control of the digestive system
Movement of materials along the digestive tract is controlled by:
Neural mechanisms
Parasympathetic (Ach) and local reflexes
Hormonal mechanisms
Enhance or inhibit smooth muscle contraction
Local mechanisms
Coordinate response to changes in pH or chemical stimuli and stretching
Direct contact of food with the mucosa can cause movement of the food along the gi tract. Additionally, the direct mechanical stimulation can lead to the glandular cells of local glands to secrete digestive juices. Epithelial stimulation also activates the enteric nervous system of the gut wall. Stimuli that cause the local mechanisms to occur are tactile stimulation, chemical irritation such as eating acidic or spicy foods, and gut wall stretching. Neural mechanisms of the enteric nervous system also cause changes in gut motility and absorption. As described earlier, the parasympathetic nervous system can modify the enteric nervous system activity by secreting acetylcholine which will lead to increases in gut motility and absorption. This is especially true of salivary glands, esophageal glands, gastric glands, the pancreas, Brunner’s glands (duodenal glands), and the glands of the distal portion of the large intestine.
There are four major GI hormones: secretin, gastrin, cholecystokinin, and gastric inhibitory peptide. These hormones are secreted in the portal circulation and exert physiological actions in target cells with receptors for the hormones. The effects of these hormones will be discussed in more detail later.

6. Digestive Enzymes Salivary glands -amylase lingual lipase Stomach
pepsin
Intestinal Mucosa
enterokinase
sucrase
maltase
lactase
amino-oligopeptidase
dipeptidase
Pancreas
amylase
trypsin
chymotrypsin
carboxypeptidase
lipase
cholesterolesterase

7. The mouth opens into the oral or buccal cavity
Primary Secretion
Alpha-amylase
Its functions include:
Analysis of material before swallowing
Mechanical processing by the teeth, tongue, and palatal surfaces
Lubrication
Limited digestion
Lingual lipase (negligible fat digestion)
Salivary amylase (limited carbohydrate digestion)
Antibodies and proteolytic enzymes
Lets now focus on the chemical breakdown of food and our story will begin with the mouth. In addition to the mechanical breakdown (chewing) of food performed with the teeth, tongue, and palate, the mouth also begins chemical breakdown of the food. Saliva contains a serous secretion and a mucous secretion. The salivary glands include the parotid, sublingual and submandibular. The parotid secretes primarily a serous secretion and the sublingual secretes primarily a mucous secretion and the submandibular secretes a combination of the two. The serous secretion contains an enzyme called alpha-amylase (or salivary amylase) and this enzyme marks the beginning of carbohydrate breakdown. There is some lingual lipase also secreted but its fat digestion is negligible. Lastly the serous secretion has antibodies and proteolytic enzymes that breakdown bacteria, virus and other microorganisms. Without this serous secretion we would have sores arising in our mouth. You secrete about a liter a day of salivary juices and these range in pH from

8. Digestion and absorption in the stomach
Short-term storage reservoir
Secretion of intrinsic factor
Pepsinogen
gastrin
Chemical and enzymatic digestion is initiated, particularly of proteins
Liquefaction of food
Slowly released into the small intestine for further processing
Before I discuss the secretions and absorption of the stomach, let me first describe the motor functions of the stomach. The motor functions of the stomach are threefold: 1) storage of food until the food can be processed in the duodenum; 2) mixing of food with gastric secretions until it forms a semifluid mixture called chyme; 3) emptying of food into the small intestine at a rate suitable for proper digestion and absorption.
The stomach relaxes when food enters it and can accommodate approximately 1.5 liters of food when completely relaxed. Each time a peristaltic wave passes over the antrum toward the pylorus, the pyloric muscle contracts which further impedes emptying through the pylorus and the food in the antrum is squirted backward toward the body of the stomach for more churning and mixing of food with gastric juices.
I will talk about the secretions of the stomach only briefly here, but will expand more on the next few slides. You will learn in more detail later that the stomach has parietal cells that secrete hydrochloric acid and intrinsic factor and you will learn that there are Chief cells that secrete pepsinogen.
Very little absorption occurs across the stomach epithelium due to the gastric mucosal barrier which is composed of the mucus secreted by mucous cells and the tight junctions in between the gastric epithelial cells. Some substances are able to be absorbed: substances like aspirin or other NSAIDS and alcohol are examples.

9. Gastric glands Gastric - HCl Pyloric - gastrin Two types glands -
(oxyntic) pepsinogen
intrinsic factor
mucus
Pyloric - gastrin

10. Gastric glands- 3 types of cells
80%
Mucous Neck cell (goblet)- release mucus to protect mucosa from acid and pepsin
Parietal cells- HCl and intrinsic factor (B12 absorption by small intestine).
Chief- numerous and release pepsinogen
The stomach has tow important types of tubular gland shown here in its mucosa: the oxyntic (acid forming or gastric gland) and the pyloric gland. The Gastric gland is found in the body and fundus. The three types of cells are mucous neck cells which secrete mainly mucus but also some pepsinogen; peptic (chief cells) which secrete pepsinogen; and parietal (oxyntic) cells, which secrete hydrochloric acid and intrinsic factor.
The pyloric glands are located in the antrum and secrete mainly mucus for protection of the pyloric mucosa but also some pepsinogen and, importantly, the hormone gastrin.
Let’s talk about the parietal cells in more detail: They secrete HCl and HCl is as necessary as pepsin for protein digestion in the stomach. They pepsinogens have no digestive activity when they are first secreted; however, as soon as they come into contact with the HCl, they are changed to form active pepsin. Parietal cells also secrete intrinsic factor which is essential for the absorption of vitamin B12 in the ileum. When acid-producing cells of the stomach are destroyed, which frequently occurs with chronic gastritis, the person develops not only achlorhydria but often also pernicious anemia owing to failure of the red blood cells to mature.
The chief cells release pepsinogen which is an enzyme released in an inactive form. HCl, with its low pH, is needed to activate the pepsionogen. Pepsin breaks down proteins into smaller peptides. But, it is the HCl that denatures the proteins—that means it merely unravels them from their quaternary and tertiary and secondary structures down to its primary structure. That means that the pepsin now has an easier time to start to break the amine bonds between adjacent amino acids.
So, you should be hearing that protein digestion begins in the stomach with the action of pepsin. Pepsinogen is secreted by Chief cells and has no enzymatic activity until exposed to the HCl acid secreted by the parietal cells. The HCl secreted has a pH of 0..8, but by the time it mixes with the stomach contents its pH climbs a bit to which happens to be the most optimal pH range for pepsin activity. Pepsin will lose its enzymatic activity at pH’s above 5. Pepsin only initiates the protein digestion, usually providing only 10-20% of total protein digestion. The majority of protein digestion is going to occur in the duodenum through enzymes secreted by the pancreas. These will be discussed later.

11. Acid production and secretionK+
Na+ H+
Cl-
H2O
osmosis
HO- +
HCO3
CO2
C.A.
Final Results
HCl mEq/L
KCl - 15 mEq/L
NaCl - 3 mEq.L
pH = 0.8 P
BLOOD
LUMEN
Gastric acid is secreted by Parietal cells under stimulation from the hormone Gastrin. Gastrin is secreted under Vagal stimulation and local enteric reflexes by the Gastrin cells also called G cells Gastrin is carried by blood to the oxyntic glands where it strongly stimulates parietal cells.
How do Parietal cells secrete hydrogen? The following is a postulated mechanism; you should know there are many postulates on this mechanism. Guyton and Hall presents a different one than the one I’m presenting here……mine’s easier to wrap your head around. Parietal cells have carbonic anhydrase, as such, the enzyme combines water and carbon dioxide into carbonic acid which dissociates into bicarbonate and H+. There is a bicarbonate/ Chloride antiporter on the basolateral side of the parietal cell and on the lumenal side active transport for Hydrogen through a H+ ATPase and chloride passively diffuses down its concentration gradient into the lumen of the stomach. The pH of this secretion can be as low as 0.8 reflecting that the hydrogen ion concentration is 3 million times that of arterial blood.
Tripe is the stomach from another animal. So, if we can eat tripe, why don’t we digest our own stomach. Well, under healthy conditions, we don’t digest our stomach for several reasons: There are many mucous neck cells that secrete a thick layer of mucus that protects the lumenal side of the stomach epithelium. Second, the simple columnar cells of the stomach epithelium has high mitotic rates. Third, there are tight junctions between the epithelial cells which prohibit the movement of digestive enzymes and acid into the interstitial space and destroy the lamina propria. Additionally, these three mechanisms also explain why the stomach does not absorb nutrients (except hydrophilic compounds that can diffuse across the mucus and cell membranes). However, these impediments to gastric absorption, or the gastric mucosal barrier, become leaky during gastritis and hydrogen is allowed to diffuse into the stomach epithelium and can lead to a gastric or peptic ulcer. Additionally chronic gastritis can cause atrophy of the gastric mucosal glandular function and lead to achlorhydria (failure to secrete HCl) or hypochlorydria (diminished HCl secretion). If parietal cells are affected, then diminished intrinsic factor is released which means less vit B12 is absorbed across the ileum and this leads to pernicious anemia.
Shown in the bottom left picture is an ulcer. At least 75% of peptic ulcer patients have recently been found to have chronic infection of the gastric and duodenal mucosa by the bacterium Helicobacter pylori. The bacterium releases digestive enzymes hat liquefy the gastric mucosal barrier and thereby allow gastric secretions to digest the epithelial cells.

12. 2 cell types of Pyloric gland
G-cells - release gastrin
Enteroendocrine cells -stimulates parietal cells to secrete acid and increases pyloric contraction; relaxes pyloric sphincter
Mucus neck cells
- mucous
20%

13. Gastric and Duodenal ulcers
Strengthens
mucus, HCO3- secretion, gastrin, PGs, epidermal growth factor
Weakens
H. pylori, aspirin, ethanol, NSAIDs,
bile salts
Peptic ulcers occur when damaging effects of acid and pepsin overcome ability of mucosa to protect itself
Gastric ulcers - main problem is decreased ability of mucosa to protect itself
Duodenal ulcers - main problem is exposure to increased amounts of acid and pepsin

14. What is the Gastric Mucosal Barrier?
alkaline mucus resists the acid and enzymes
Tight junctions-gastric juice can’t seep into lamina propria
Epithelial cell replacement- 3-6 day life span.
Physiological - diffused H+ ions are transported back to lumen
Damaged Gastric Mucosal Barrier
H+ back-leaks into mucosa in exchange for Na+. This is a forerunner to gastric ulcer -
Decreased cell pH leads to cell death
Damaged mast cells (ECL cells) leak histamine
Viscous cycle Histamine .. vascular damage .. local ischemia .. greater leakage of H+.. more cell death ...

15. Helicobacter pylori
H. pylori found in 95% patients with DU and 100% patients with GU (when alcohol, aspirin, NSAIDS are eliminated)
Gram negative bacterium
High urease activity - high NH4+ activity
- can withstand acid environment
- NH4+ damages epithelial cells (GU)
- Increases acid secretion (DU)

16. Treatment of Peptic Ulcers
Antacids
H2 receptor blockers - Rantidine (Zantac)
- Cimetidine (Tagamet)
Proton pump inhibitors - Omeparazole (Prilosec)
Antibiotics
Surgical (rare) - vagotomy
- antrectomy

17. Stimulation of acid secretion
Seeing, smelling and anticipating food is perceived in brain. Brain tells stomach to prepare for receipt of meal
Accounts for 30% of acid response to meal
Gastric secretion is stimulated by local (distention), neural, and endocrine mechanisms
Acetylcholine - HCl secretion
- mucus, pepsinogen, and gastrin
Histamine HCl secretion
Gastrin HCl secretion (1500x more powerful compared to histamine)
60%
10%

18. Small intestine Important digestive and absorptive functions
Secretions and buffers provided by pancreas, liver, gall bladder
Three subdivisions:
Duodenum
Jejunum
Ileum
Ileocecal sphincter
Transition between small and large intestine
Once the chyme leaves the stomach through the pylorus, it enters the small intestine. The three parts of the small intestine include the duodenum, jejunum, and ileum. The duodenum is the site where the chyme enters from the stomach and it is here that pancreatic, hepatic, and intestinal secretions will meet to start processing the chyme. These secretions will be discussed in detail in subsequent slides.
There are three parts to the small intestine. Starting from the proximal end near the stomach is the duodenum. The middle portion is the jejunum, and the part leading to the large intestine is the ileum. The sphincter that controls one-way movement of the chyme into the large intestine is the ileocecal valve. On the ileum side, chyme is found in the lumen, once the chyme passes through the ileocecal valve into the large intestine, it is now called feces.

19. Histology of the small intestine
Plicae
Transverse folds of the intestinal lining
Villi
Fingerlike projections of the mucosa
Lacteals
Terminal lymphatic in villus
Microvilli
Brush border: increases surface area 20-fold
Lets look at the small intestine more carefully. First, there are two macroscopic structures: plicae circulares (known also as folds of Kerckring) and villi. Plicae circulares increase the surface area of the absorptive mucosa about 3 fold. These folds promote a tumbling action of the chyme to allow proper mixing of the chyme with digestive enzymes. They work in a similar way to the projections in your clothes dryer that promote tumbling of your clothes so that warm air has more contact with your clothes. There is another macroscopic structure that increases surface area in the small intestine as well: the villi. The villi are an extension of the mucosal surface and can project up to 1 mm from the mucosa into the lumen. Their presence enhances the surface area 10-fold. The microvilli are the extensions of the cell membrane from individual simple columnar cells on the surface of the villi; they create the brush border. Within these microvilli digestive enzymes secreted by the epithelial cells accumulate and further increases surface area. Over all, these three modifications increase your absorptive area almost by 1000 fold.

20. Intestinal glands
secretin to stimulate pancreas to release bicarbonate mucus
cholecystokinin to stimulate pancreas and gallbladder
Gastric Inhibitory peptide (GIP)- inhibits gastrin secretion and decreases stomach emptying
Duodenal glands- bicarbonate mucus.
The four major GI hormones are Gastrin, Cholecystokinin, and Gastric Inhibitory Peptide. I have briefly discussed gastrin, but will elaborate further here: Gastrin is secreted by the G cells (Gastrin cells) of the antrum of the stomach in response to stretch of the stomach and the presence of peptides or amino acids or under nervous stimulation from the vagus or the enteric nervous system. It stimulates the parietal cells to secrete HCl.
The remaining 3 hormones are secreted by intestinal glands of the small intestine, specifically the duodenum and/or the jejunum. Secretin is secreted by the duodenum in response to acidic gastric juice emptying into the duodenum. Secretin promotes pancreatic secretion of bicarbonate mucus from the pancreas. It also promotes pespin secretion from Chief cells and inhibits gastric acid secretion by parietal cells. Gastric inhibitory peptide is secreted by the mucosa of the duodenum and jejunum, mainly in response to fatty acids and amino acids. Its job is to inhibit gastric acid secretion and slows the emptying of the gastric contents into the duodenum. CHoleycystokinin is secreted by the cells of the duodenum and jejunum mainly in response to digestive products of fat, fatty acids, and monoglycerides in the intestinal contents. Cholecystokinin stimulates pancreatic enyzme secretion and gallbladder contraction so that the bile stored in the gallbladder is released into the duodenum and can emulsify fats.
Not a hormone, but still found within the intestinal glands are duodenal glands (also called Brunner’s glands) and these secrete bicarbonate mucus so that the acidic contents of the stomach do not promote digestion of the intestinal mucosa.
Right about now I’d like to take some time to revisit metabolic acidosis and alkalosis. Remember that we learned that vomiting of gastric juices causes metabolic alkalosis due to the loss of Hydrogen through vomiting and the synthesis of new bicarbonate by the parietal cell. If there is excessive diarrhea this leads to metabolic acidosis due to the loss of bicarbonate mucus from the intestine and pancreas and concomitant untitrated hydrogen that remains in the body. IF a person vomits from the duodenum, then there is loss of both bicarbonate buffer and gastric juices and there usually isn’t an acid base problem that results—again, we need a net loss of one or the other, hydrogen or bicarbonate, in order to see an imbalance in acid/base chemistry.

21. The Activities of Major Digestive Tract Hormones
Let’s do the hormones again, this time with the big picture involved. Once food enters the stomach, the G-cells within the gastric glands of the antrum release Gastrin. Gastrin stimulates the parietal cells to release more acid and also promotes more motility of the stomach. This means the contents of the stomach are churned and mixed to form chyme. Next, the chyme travels through the pylorus and enters the duodenum. The presence of chyme now triggers the release of the other 3 major digestive tract hormones: cholecystokinin, secretin, and gastric inhibitory peptide. Secretin stimulates the pancreas to release bicarbonate rich buffer. Gastric inhibitory peptide primarily slows down stomach motility and slows the rate at which the stomach empties chyme into the duodenum. Cholecystokinin stimulates the liver, gallbladder and pancreas. The liver and gallbladder are stimulated to secrete and release, respectively, bile into the duodenum through the hepatopancreatic ampulla. CCK stimulates the pancreas to release its digestive enzymes that include enzymes for carbohydrate digestion, lipase, nucleases, and peptidases. All four hormones stimulate the pancreas to release insulin in a sort of “anticipatory” effect for food. The insulin then stimulates insulin dependent cells of the body to start inserting glucose transport proteins into the cell membranes. These glucose transporters bind to glucose and facilitate its movement from the plasma to the cytoplasm. OF the four hormones, Gastric inhibitory peptide seems to have the strongest influence on insulin release.
Figure 24.22

22. Small Intestine- digestive enzymes
Maltase- splits maltose into 2 glucose units
Lactase- splits lactose into glucose and galactose
Sucrase- splits sucrose into glucose and fructose
Peptidase- breaks down small peptides into amino acids
Intestinal lipase- breaks down triglycerides into free fatty acids and monoglycerides
Enterokinase- Activates trypsinogen to trypsin (trypsin then activates chymotrypsinogen and procarboxypeptidase)
In the brush border of the small intestinal cells one can isolate several different enzymes that help in digestion. First, there are a few enzymes involved in carbohydrate digestion such as maltase, lactase, and sucrase. These enzymes basically split larger sugars (tri and disaccharides) into monosaccharides. There is also an intestinal peptidase. A peptidase breaks down small peptides into individual amino acids. There is also an intestinal lipase that digests triglycerides into free fatty acids and monoglycerides.
Lastly, and this is really important, there is an enzyme called enterokinase. This job has the important job of activating a pancreatic enzyme, trypsinogen, into active trypsin. Once trypsin has been formed, then it can activate its cousin enzymes, also secreted by the pancrease). These enzymes include chymotrypsinogen and procarboxypeptidase. I will have further discussion of these enzymes towards the end of this lecture.

23. Pancreas As chyme floods into small intestine two things must happen:
Acid must be neutralized to prevent damage to duodenal mucosa
Macromolecular nutrients - proteins, fats and starch must be broken down much further so their constituents can be absorbed
Pancreas plays vital role in accomplishing both objectives
Digestive enzymes for all food types
Bicarbonate solution to neutralize acid chyme

24. Regulation of Pancreatic Secretion
Secretin and CCK are released when fatty or acidic chyme enters the duodenum
CCK and secretin enter the bloodstream
Upon reaching the pancreas:
CCK induces the secretion of enzyme-rich pancreatic juice
Secretin causes secretion of bicarbonate-rich pancreatic juice
Vagal stimulation also causes release of pancreatic juice
I want to go over again the control over the exocrine function of the pancreas. When fatty or acidic chyme from the stomach arrives in the duodenum, hormones released from the intestinal gland will signal the pancreas to release its secretions.
Secretin stimulates the pancreas to release the bicarbonate rich pancreatic juice to neutralize the stomach acids.
Cholecystokinin will stimulate the pancreas to release its digestive enzymes that can digest lipids, nucleic acids, carbohydrates and proteins.
In addition to this hormonal control over the pancreas, stimulation of the parasympathetic system can also cause the pancreas to release its secretions. This parasympathetic stimulus would be conveyed through the Vagus nerve (or Cranial nerve number 10) and its interesting how the stimulus arrives.
The vagus nerve actually carries impulses to the digestive tract starting with the moment you see or even think about food. For example, 30% of the response to a meal is initiated by the anticipation of eating and the odor and taste of food. The vagus carries impulses to the stomach and GI tract and stimulates them—the stomach starts to secrete HCl. The gastric phase accounts for 60% of the acid response to a meal. It is initiated by distention of the stomach which leads to nervous stimulation of gastric secretion. During these first two phases, the vagus nerve is also transmitting stimuli to the pancreas and the pancreas is starting to secrete bicarbonate juices and enzymatic secretions in anticipation of chyme arriving soon. Then, the intestinal phase accounts for the last 10% and is initiated again by nervous stimuli associated with distention of the small intestine.

25. The Pancreas Exocrine function (98%) Endocrine function –
Acinar cells make, store, and secrete pancreatic enzymes
Endocrine function –
( cells) release somatostatin (inhibitory to gastrin and insulin and glucagon)
β-cells –release insulin
α-cells-Release glucagon
Although the stomach has an enzyme to start protein digestion, and the small intestine has multiple enzymes within its brush border for carbohydrate digestion, protein digestion, and lipid digestion, the organ that releases the most substantial digestive enzymes is the pancreas. 98% of its physiology is dedicated to an exocrine function in the synthesis and release of digestive enzymes by the Pancreatic Acini (that’s the cell type in the pancreas that makes these enzymes—and I will cover all of these in the next few slides.
The remainder of the pancreas is dedicated to an endocrine function with the production and secretion of hormones into the blood stream. These hormones include insulin (which stimulates insulin dependent cells of the body to express glucose transporters and then glucose can be imported within the cell’s cytoplasm. As glucose leaves the blood plasma and enters insulin dependent cells, the blood plasma glucose levels declines. Insulin is synthesized and released by the Beta-cells of the Islets of Langerhans.
In contrast, when blood glucose levels decline too much, the alpha-cells of the islets of Langerhans release glucagon which stimulates the liver to cleave glycogen (a polymerized form of glucose) into single monomers of glucose.
There are other endocrine cells within the Islets of Langerhans (delta cells for example) that release hormones like somatostatin which is a hormone that shuts down all hormonal functions of the kidney and stops gastrin.

26. The Pancreas as an Endocrine Gland
Insulin
Beta cells
Skeletal muscle and adipose tissue need it to make glucose receptors
Promotes glucose uptake
Prevents fat and glycogen breakdown and inhibits gluconeogenesis
Increases protein synthesis
Promotes fat storage
Epi/Norepi inhibit insulin!
Help maintain glucose levels during times of stress and increase lipase activity in order to conserve glucose levels
Insulin is the only hormone known to have a direct effect in lowering blood glucose levels. It is synthesized and released into the blood stream by the beta cells of the islets of Langerhans. Most tissues of the body, like skeletal muscle and adipose tissue are insulin dependent in order to move glucose into the body tissues. The main exception is the brain. Because most cell membranes are impermeable to glucose, they require a special carrier, called a glucose transporter, to move glucose from the blood into the cell. Within seconds of binding insulin, the membranes fo about 80% of body tissues increase their uptake of glucose by means of special glucose transporters. This is particularly true of skeletal muscle and adipose tissue.
In addition to promoting glucose uptake, insulin prevents fat and glycogen breakdown and inhibits gluconeogenesis, and increases protein synthesis. Gluconeogenesis means the synthesis of new glucose molecules by converting amino acids or glycerol into new glucose molecules. Insulin also promotes fat storage by increasing the rate of movement of glucose into fat cells which is then converted into fat. Insulin also inhibits protein breakdown and increases protein synthesis.
As a side note: catecholamines (like epi/norepi) help to maintain blood glucose levels during periods of stress. Epinephrine inhibits insulin release and promotes glycogenolysis by stimulating the conversion of muscle and liver glycogen to glucose. Muscle glycogen cannot be released into the blood; nevertheless, the mobilization of these stores for muscle use conserves blood glucose for use by other tissues such as the brain and the nervous system. During periods of exercise and other types of stress or fear, epinephrine inhibits insulin release from the beta cells and thereby decreases the movement of glucose into muscle cells. The catecholamines also increase lipase activity and thereby increase mobilization of fatty acids, a process that conserves glucose. The blood glucose-elevating effect of epinephrine is an important homeostatic mechanism during periods of hypoglycemia in insulin-treated patients with diabetes. I will talk about Diabetes Mellitus type 1 and type II in the next two slides.
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27. The Pancreas as an Endocrine Gland
Glucagon
Maintains blood glucose between meals and during periods of fasting.
Nervous tissue (brain) do not need insulin; but are heavily dependent on glucose levels!
Increases blood glucose levels.
Initiates glycogenolysis in liver (within minutes)
Stimulates amino acid transport to liver to stimulate gluconeogenesis
Glucagon is a polypeptide molecule produced by the alpha cells of the islets of Langerhans and maintains blood glucose levels between meals and during periods of fasting. The most dramatic effect of glucagon is its ability to initiate glycogenolysis or the breakdown of liver glycogen as a means of raising blood glucose, usually within a matter of minutes. Glycogenolysis means that the liver hydrolyzes glycogen to release free glucose molecules into the blood stream.
Although many tissues and organ systems are able to use other forms of fuel, such as fatty acids and ketones, the brain and nervous system rely almost exclusively on glucose as a fuel source. Because the brain can neither synthesize nor store more than a few minutes’ supply of glucose, normal cerebral function requires a continuous supply from the circulation. Severe and prolonged hypoglycemia can cause brain death and even moderate hypoglycemia can result in brain dysfunction.
Glucagon also increases the transport of amino acids into the liver and stimulates their conversion into glucose.
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28. Disorders of the Pancreas: Diabetes Mellitus
Gestational Diabetes
Type I diabetes – develops suddenly, usually before age 15
Destruction of the beta cells
Skeletal tissue and adipose cells must use alternative fuel and this leads to ketoacidosis
Hyperglycemia results in diabetic coma
Diabetes Mellitus is a chronic health problem affecting more than 18 million people in the United States. There are 800,000 new cases of diabetes per year; almost all of these are type 2 diabetes. Diabetes is a significant risk factor in coronary heart disease and stroke, and it is the leading cause of blindness and end-stage renal disease, as well as a major contributor to lower extremity amputations.
Type I diabetes develops when the beta cells have been destroyed, say from an autoimmune response, or an environmental triggering event (like an infection). These patients, therefore, lack the ability to make sufficient insulin. Because of this, the insulin dependent cells of the body (skeletal muscle and adipose tissue) can not insert their glucose transporters into their cell membranes. Even though the patient has ingested sufficient glucose, the skeletal muscle and adipose cells can not internalize the glucose and then resort to using fatty acids and proteins as fuel sources. These cells are literally starving in the face of plenty. Because these cells use alternative fuel sources that feed into metabolic pathways used by glucose, they generate many ketone bodies (this process will be discussed during your metabolism lecture). Because ketones are organic acids, they cause ketoacidosis when they are present in excessive amounts. These events can lead to diabetic coma due to the inability of the glucose to enter the insulin dependent cells of the body.
The patient will need to take insulin for the remainder of their lifetime and need to regulate its use carefully—an overdose of insulin would result in hypoglycemia and now insulin independent cells (like the brain tissue) would not have any fuel and this would also result in diabetic coma.

29. Disorders of the Pancreas: Diabetes Mellitus
Type II diabetes and metabolic syndrome– adult onset
Usually occurs after age 40
Cells have lowered sensitivity to insulin
Controlled by dietary changes and regular exercise
As I said earlier, the majority of the new cases of diabetes mellitus constitute the type II variety- this is usually associated with adult onset, although more and more of our obese children are presenting with type II. Type 2 diabetes describes a condition of hyperglycemia despite the availability of insulin. Among the acquired risk factors I mention in slide 25, obesity and physical activity are of paramount importance. Obese people have increased resistance to the action of insulin and impaired suppression of glucose production by the liver, resulting in both hyperglycemia and hyperinsulinemia. Central obesity (or abdominal fat) is more closely linked with insulin resistance than is peripheral obesity (gluteal/subcutaneous). The metabolic abnormalities that lead to type 2 diabetes include: peripheral insulin resistance, deranged secretion of insulin by the pancreatic beta cells, and increased glucose production by the liver.
I’d like to talk further about insulin resistance and the metabolic syndrome: there is increasing evidence to suggest that when people with type 2 diabetes present predominantly with insulin resistance, the diabetes may represent only one aspect of a syndrome of metabolic abnormalities. Hyperglycemia in these people is frequently associated with obesity, high levels of plasma triglycerides and low levels of high-density lipoproteins (HDL), hypertension, systemic inflammation, abnormal fibrinolysis, abnormal funciton of the vascular endothelium, coronary artery disease, cerebrovascular disease, and periopheral arterial disease. This constellation of abnormalities often is referred to as the insulin resistance syndrome, syndrome X, or the preferred term, metabolic syndrome.
The best treatment for these people is to lose weight and mange their diet-studies have shown with these changes that insulin sensitivity can return.

30. You need to start appreciating the following concept before your metabolism lecture.
DNA and RNA are polymers. That means they are long strands of monomers that have been bound together. What are the monomers of nucleic acids? The nucleotides: adenine, guanine, thymine, cytosine, and uracil. When the individual monomers are linked together, this occurs by dehydration synthesis, that means a water is lost- one nucleotide loses an OH group and the other nucleotide loses a hydrogen.
Same concept applies to protein synthesis: individual monomers (amino acids) are bound together through dehydration synthesis. This bond between amino acids is called a peptide bond.
Yes, the same applies when making triglycerides: a glycerol has 3 OH groups and each one can have a fatty acid linked to it by dehydration synthesis.
Care to guess how individual glucose molecules are linked together to create glycogen (the polymer of glucose that is created by the liver to store glucose for the body)? That’s right, dehydration synthesis. Now, you have just eaten in your meal a whole bunch of polymers: carbohydrates, proteins, fats, and even nucleic acids. Your GI tract has to break these polymers down into individual monomers for two good reasons: One, the polymers are too big to get through the cell membrane so they have to be cleaved into their monomers. The monomers are absorbed across the epithelial lining following sodium’s diffusion by using secondary active transport. The second reason: by taking one large polymer and breaking it down to individual monomers and then absorbing the multiple monomers, water will follow this osmotic gradient and your body can absorb a tremendous amount of water this way.
So, This is a list of the digestive enzymes secreted by the pancreatic acini. The more important enzymes for digestion of proteins include trypsin, chymotryprsin, and carboxypeptidase which are secreted in the inactive forms of trypsinogen, chymortrypsinogen, and procarboxypeptidase. I want to take some time to discuss these special enzymes more. Because their names end with the suffix ‘ogen’ or begin with the prefix “pro” this should tell you that these enzymes are zymogens- or inactive precursors. What will activate them into their functional forms? Well, the small intestinal glands release an enzyme called enterokinase and it is this enzyme that cleaves trypsinogen into its active form: trypsin. Once trypsin is formed then it can activate its 2 partners into chymotrysin and carboxypeptidase. It is important that the proteolytic enzymes of the pancreas don’t become activated until after they have been secreted into the intestine because the trypsin and the other enzymes would digest the pancreas itself leading to a very painful condition called pancreatitis. Fortunately, the same cells in the pancreas that make these enzymes also make another substance called trypsin inhibitor and it inhibits the activity of trypsin. Why just trypsin? Turns out that trypsinogen has an autocatalytic effect and can convert itself into active trypsin which then activates the other two peptidases. When the pancreas becomes severely damaged or when a duct becomes blocked, large quantities of pancreatic secretion sometimes becomes pooled in the damaged areas of the pancreas and the trypsin inhibitor is often overwhelmed. The trypsinogen autocatalytically converts itself and within a few hours the pancreas is being digested: this is called acute pancreatitis and it is life-threatening.
The pancreatic enzyme for carbohydrates is pancreatic amylase, which hydrolyzes starches, glycogen and most other carbohydrates (except cellulose) to form disaccharides and a few trisaccharides.
The main enzyme for fat digestion is pancreatic lipase, which hydrolyzes neutral fat into fatty acids and monoglycerides; cholesterol esters; and phospholipase, which splits fatty acids from phospholipids.
There are also pancreatic nucleases that can break down both Ribonucleic acids and Deoxyribonucleic acids.
As you experienced in your digestive system physioEx lab, these enzymes are substrate specific-which means they only have action on a particular polymer and the enzymes are all hydrolases which means they use water to break bonds that connect the monomers to form polymers. Doesn’t that make sense? If dehydration synthesis was used to make the polymer, then hydrolysis is used to break up the polymer into monomers. You also learned in physioEx that the activity of the enzymes is dependent on temperature and pH.
The pancreatic enzymes would be denatured right away and lose activity if the stomach acid was not neutralized. Well, the pancreas has this covered, too! Notice that the pancreas secretes copious amounts of sodium bicarbonate to neutralize stomach acids and generate a pH to allow the efficient enzymatic activity.

31. Pancreatic Failure
Digestion is abnormal when pancreas fails to secrete normal amounts of enzymes.
Pancreatitis
Removal of pancreatic head - malignancy
Without pancreatic enzymes -
60% fat not absorbed (steatorrhea)
30-40% protein and carbohydrates not absorbed

32. Pancreatitis Chronic pancreatitis - (multiple shared causes)
Pancreatitis means inflammation of pancreas. Autodigestion theory can explain condition.
Chronic pancreatitis - (multiple shared causes)
alcohol most common cause in adults
cystic fibrosis - most common cause in childre
CF patients lack chloride transporter at apical membrane.
Watery ductal secretion decreases which concentrates acinar secretions in ducts.
Precipitation of proteinaceous secretions block ducts and can destroy gland by autodigestion.
Acute pancreatitis - (multiple shared causes)
Gallstones - most common cause

33. Absorption of digested polymers is linked to Salt Absorption in Small Intestine
Sodium is absorbed across apical cell membrane by 4 mechanisms -
1. Diffusion - through water-filled channels
2. Co-transport - with AA and glucose
3. Co-transport - with chloride
4. Counter-transport - in exchange for H+
Chloride follows electrical gradient created by absorption of sodium

34. Sodium Absorption in Small Intestine
Na+ S
Cl- H+ P K+ 1 2 3 4
Aldosterone increases
Na+ reabsorption and K+ secretion in S.I. and colon.

35. Chemical Digestion: Carbohydrates
Begins in the mouth (minimal) and mostly occurs in small intestine when pancreatic enzymes are released
Absorption of monosaccharides occurs across the intestinal epithelia Absorption: via cotransport with Na+, and facilitated diffusion
Enter the capillary bed in the villi
Transported to the liver via the hepatic portal vein
Enzymes used: salivary amylase, pancreatic amylase, and brush border enzymes (maltase, lactase, and sucrase)
lumen
So let’s have a quick review for the digestion of carbohydrates and where it occurs. First, carbohydrate digestion begins in the mouth with salivary amylase and there is no absorption that occurs here. Salivary amylase breaks down starch into a disaccharide called maltose. Once the smaller carbohydrates reach the stomach, the acidic environment stops the activity of salivary amylase. Once the chyme enters the small intestine, now there are several enzymes found in the brush border that can digest carbohydrates such as maltase, lactase, and sucrase. Additionally, the pancreas releases copious amounts of pancreatic amylase- which works like the salivary amylase and breaks down carbohydrates to the small disaccharide, maltose.
Once the maltose has been broken down into 2 molecules of glucose, now glucose can be transported across the small intestine epithelium. Glucose is transported by a sodium co-transport mechanism. As I describe the events, feel free to draw this in the picture above showing two small intestine epithelial cells with their microvilli. Just like in the kidney, there are two stages in the transport of sodium through the intestinal membrane. First is the active transport of sodium ions through the basolateral membranes of the epithelial cells into the blood using the sodium/potassium ATPase. As the sodium levels inside the cell decrease, this creates an electrochemical gradient for sodium to enter the cell through the apical side that faces the lumen. This decrease of sodium inside the cells causes sodium from the intestinal lumen to move through the brush border of the epithelial cells to the cell interiors by a process of facilitated diffusion. In the case of glucose, sodium binds to a transporter and is allowed to diffuse down its electrochemical gradient and as it does, energy from this process allows glucose to be pulled into the cell. So, this secondary active-transport is initiated by the active transport of sodium through the basolateral membranes of the intestinal epithelial cells and provides the motive force for the moving of glucose through the membranes.
This same secondary active transport mechanism will occur for absorbing amino acids and nucleic acids in the lumen. I will review the process (again) for amino acids, but not for nucleic acids as you really should have mastered this concept of secondary active transport by now.

36. Chemical Digestion: Proteins
Absorption: similar to carbohydrates (sodium co-transport)
Enzymes used: pepsin in the stomach
Enzymes acting in the small intestine
Pancreatic enzymes – trypsin, chymotrypsin, and carboxypolypeptidase (these must be activated!)
Brush border enzymes – peptidases
So, let’s review the digestive process for amino acids. The digestion process for protein first begins in the stomach with activation of pepsinogen by HCl into pepsin. Once the chyme enters the small intestine, the bicarbonate rich buffers neutralize the stomach acid and pepsin loses activity. Now, there are pancreatic enzymes, such as trypsin, chymotrypsin, and carboxypolypeptidase (which I will discuss more later) that are present and can digest proteins into smaller peptide chains. Additionally, the brush border enzymes like aminopeptidase, carboxypeptidase, and dipeptidase digest the peptides into single amino acids, dipeptides or tripeptides.
This picture shows the amino acids, dipeptides and tripeptides, moving across the epithelium of the intestine on their own. But, you and I both know that this does not happen. Rather, the energy for most of this transport is supplied by a sodium co-transport mechanism in the same way that sodium co-transport of glucose occurs. That is, the sodium-potassium ATPase on the basolateral side of the epithelial cells removes sodium from the cell and establishes an electrochemical gradient. ON the luminal side, there is a sodium- amino acid co-transporter. Here, sodium binds to the transporter as does the amino acid (or dipeptide or tripeptide) and then sodium moves down its electrochemical gradient to the interior of the cell and pulls the amino acid or small peptide along with it.

37. Lipid digestion and absorption
Lipid digestion utilizes lingual and pancreatic lipases, cholesterol esterase (cleaves ester bond to release cholesterol) and phospholipases release fatty acids and monoglycerides.
Bile salts improve chemical digestion by emulsifying lipid drops
Lipid-bile salt complexes called micelles are formed
I’d like to start the discussion of this slide with addressing the role of bile salts. Simply put, bile salts form micelles, which are small spherical cylindrical globules– shown here as the small structures at the bottom of the picture. These develop because each bile salt molecule has a fat-loving sterol group (i.e., it is hydrophobic) and a water loving group (hydrophilic) The fat loving portion surrounds a portion of the ingested fat globule and the water-loving portions will project outward to cover the surface of the micelle. Because these polar groups are negatively charged, they allow the entire micelle globule to dissolve in the water of the digestive fluids in the small intestine and remain in solution until the fat is digested and the fatty acids absorbed in the blood. The micelles are important for ferrying the resulting fatty acids and monoglycerides to the brush border, and once the fats are absorbed by the blood then the bile salts can be reused to ferry more digested fats to the brush border.
So, once the bile salts form micelles of fat droplets, the cholesterol esters and phospholipids we consumed in our diet are broken down by cholesterol esterase and phospholipase, respectively. These enzymes release free cholesterol and fatty acids.
I will leave this slide with a stern caution: bile salts from the liver and gallbladder do NOT DIGEST INJESTED FATS! Rather, they only emulsify the fats—packaging into smaller portions to increase the surface area so that the lipases have an easier time digesting the fats.

38. Fatty Acid Absorption
Fatty acids and monoglycerides enter intestinal cells via diffusion; bile salts can be reused to ferry more monoglycerides
They are combined with proteins within the cells
Resulting chylomicrons are extruded
They enter lacteals and are transported to the circulation via lymph
As I said in the previous slide, the bile salt micelles transport monoglycerides and fatty acids to the brush border. The digested fats diffuse into the epithelial cells. The fatty acids are used to form triglycerides and combine with proteins to form chylomicrons. CHylomicrons then transport the phospholipids to the underlying lacteal vessel which then transports the chylomicrons back to the circulating venous blood. The half life of a chylomicron is about 1 hour and most of the chylomicrons are removed from the circulating blood as they pass through the capillaries of adipose tissue or the liver. Adipose tissue and liver both contain large quantities of the enzyme lipoprotein lipase. Once the free fatty acids cross the cell membrane, they are resynthesized into triglycerides so they can be stored in the cells.
If free fatty acids need to be released from storage cells like adipocytes, then the triglycerides are hydrolyzed into free fatty acids and glycerol (we will discuss hydrolysis during your metabolism lecture). And free fatty acids are transported by albumin for the body’s energy needs.
In the post-absorptive state, the lipids are then transported in plasma in the form of lipoprotein. You’ve heard of “good cholesterol” and bad cholesterol. These terms are really referring to lipoproteins. HDL stands for high density lipoprotein and it is high density because there is mostly protein in this molecule and fewer fats. LDL stands for low density lipoprotein and this molecule has many more fats transported within it—hence the term “bad cholesterol.” The LDL transport triglycerides synthesized by the liver mainly to adipose tissue, whereas the HDL are important for the different stages of phospholipid and cholesterol transport from the liver to the peripheral tissues or from the peripheral tissues back to the liver. I always remember that HDL is the “good cholesterol” for two reasons: It contains more protein than fat and the fats being transported are either going to be used by the cells of the body for energy or removed from the body by the liver and expelled into the gi tract. LDL is “bad cholesterol” because it contains mostly fats and is merely transporting them to adipocytes for storage. Thus, we want a greater HDL to LDL ratio. Having a high HDL to LDL ratio also prevents atherosclerosis. Atherosclerosis is a disease of the large and intermediate-sized arteries in which fatty lesions or plaques, develop on the inside surfaces of the arterial walls. So how can you help your body excrete more fats? Eat more fiber. Remember the fiber is going to keep the fats soluble in the gi tract and makes it easier to defecate. IF you have pure fats being excreted from the gi tract this is called steatorrhea, an upleasant fatty diarrhea.

39. Sprue
Diseases that result in decreased absorption even when food is well digested are often classified as “sprue” -
- Nontropical sprue - also called celiac disease
- allergic to gluten (wheat, rye)
- destroys microvilli and sometimes villi
- Tropical sprue - bacterium (?)
- treated with antibacterial agents
Steatorrhea - if stool fat is in the form of FFA - digestion has occurred

40. Fluid Entering and Exiting the Gut
Volume
entering
Volume
absorbed 10
95% of water is absorbed in the small intestines by osmosis
Water moves in both directions across intestinal mucosa
Net osmosis occurs whenever a concentration gradient is established by active transport of solutes into the mucosal cells
Diet (2)
Duodenum
and
Jejunum (4) 8
Saliva (1)
Volume (L/day) 6
Stomach
(2)
Ileum
(3.5) 4
Bile (1)
Pancreas (1) 2
Volume
Excreted ml
S.I. (2)
Colon (1.4)

41. The Liver Digestive function – bile production; emulsifies fats
Bilirubin- decomposed hemoglobin
Urobilinogen- by-product of bilirubin metabolism
bile salts- keep cholesterol dissolved in bile
Performs many metabolic functions- stores vitamins, processes fats, detoxifies,
makes blood proteins
It is said that the liver provides over 500 services for the body.....thank goodness we don’t have time to discuss all the functions of the liver. So, lets review a few key functions of the liver. First, you already know that it detoxifies your blood through the hepatic portal system, stores vitamins like vit B 12 and another coenzyme called folic acid. It also processes fats through B-oxidation (a process that will be described in your metabolism lecture) and can convert glycerol and amino acids into new glucose molecules through gluconeogenesis. The liver is also responsible for making most of your blood plasma proteins (albumin being the most significant). The liver also makes most of your clotting factors. In this powerpoint I hope you now appreciate that the liver makes bile and the bile is secreted. If the hepatopancreatic sphincter leading from the hepatopancreatic ampulla is closed, then the bile backs up to the gallbladder where it is stored and concentrated. Remember, bile does not have any digestive enzymes associated with it. Bile merely emulsifies fats in order to increase the surface area for lipase activity.

42. Physiology of the large intestine
Reabsorption in the large intestine includes:
Water and electrolets
Bacteria make: Vitamins – K, biotin, and B5
Organic wastes – urobilinogens and sterobilinogens
Bile salts
Toxins
Mass movements of material through colon and rectum
Defecation reflex triggered by distention of rectal walls
By the time our chyme passes through the ileocecal valve, the volume has diminished from 9L down to 1200ml. In the large intestine, the proximal half of the colon is important for absorption of electrolytes and water. The mucosa of the large intestine has a high capability for active absorption of sodium, and the electrical potential created by absorption of sodium causes chloride absorption as well. The tight junctions of the large intestine are tighter than those of the small intestine, which decreases back diffusion of ions through these junctions. This allows the large intestinal mucosa to absorb sodium ions against a higher concentration and prevents back leak of ions into the lumen. Thus the absorption of sodium and chloride ions creates an osmotic gradient across the large intestinal mucosa, which in turn causes absorption of water. The large intestine can reabsorb about 5-7 liters of fluid and electrolytes a day. If the total quantity of chyme entering the large intestine is greater than this, then the excess appears in the feces as diarrhea.
What is in feces? It is about 30% dead bacteria, percent fat, percent inorganic matter, 2-3 percent protein, and 30% undigested roughage of food and bile and sloughed epithelial cells. The brown color is from the stercobilin and urobilin, which are derivatives of bilirubin.
This concludes our discussion on the physiology of the digestive tract.

43. Figure 8-18 Agents that stimulate and inhibit H+ secretion by gastric parietal cells. ACh, Acetylcholine; cAMP, cyclic adenosine monophosphate; CCK, cholecystokinin; ECL, enterochromaffin-like; IP3, inositol 1,4,5-triphosphate; M, muscarinic.
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© 2005 Elsevier

44. Figure 8-19 Regulation of HCl secretion during cephalic and gastric phases. ACh, Acetylcholine; GRP, gastrin-releasing peptide (bombesin).
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© 2005 Elsevier

45. Figure 8-20 Balance of protective and damaging factors on gastroduodenal mucosa. H. pylori, Helicobacter pylori; NSAIDs, nonsteroidal anti-inflammatory drugs.
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© 2005 Elsevier

46. Figure 8-15 Secretory products of various gastric cells.
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© 2005 Elsevier