Editing Digestive system, Metabolism

*started here on 04/19/10.

==The digestive system==
*Sedentary body requireds ~30 kcal / kg body weight per day.

===Functions of the digestive system===
*Ingestion, getting food in.
*Secretion, we'll talk about all the secretions. (pancreas, liver, gall bladder, stomach acid, salivery glands).
*Digestion proper
**Three different parts:
***Mechanical: physical breakdown
***Chemical breakdoyn, different than enzymes; think HCL in the stomach, not enzymes like in the small intestine.
***Enzymatic; more specific.
*Absorption, that is how do we get the nutrients from lumen into blood.
*Defectation; getting rid of stuff that isn't useful.

*We're gong to think about microvilli to maximize absorption, peristalsis (mixing and physical breakdown).

===Major components===
*The tube.
*Accessory structures that protude into it or communicate with it via ducts.

====Oral cavity====
*There is a surface lining called the mucosa
**There is lots of friction and abrasion so we want something that is stratified, so we have a stratified epithelial that is non-keratinized.
**It is moist.
**Some areas are keratinized where abrasion is occuring: surface of the tongue, hard pallat, too.

=====Tongue=====
*Intrinsic and extrinsic muscles.
*Extrinsic anchor muscle in mouth, way back to the highway bone.  These are responsible for the general movement of the tongue and for formation and movement of the bolus.
*Intrinsic muscles are responsible for shaping the tongue for things like speach.
*Taste buds on the surface of the tongue has receptor cells.
**These occur in the papillae of the tongue.

=====Salivary glands=====
*We have three major areas of where we find salivary glands: sublingual ducts, submandibular, and paratoid.
*Not all generate the same amount.
*Minor ducts are located around the lips and throat.
*Stones in the salivary glands can be very painful.
*The internal structure is similar between types.
*Along the sides of the ducts are cells that form the acinus (plural acini).
*Serous cells are watery.  Glucocells are thicker.
**These two cell typhes generate the saliva.
**You can determine which type they are by histology.

=====Saliva=====
*You produce 1.5L per day (up to 2L).
*Secretions from different glands aren't necessarily of the same composition.
*Also, the ion composition will change based on the flow rate (as it goes up, NaCL release increases).
*Saliva is slightly acidic; this correlates with the preferable pH of alpha amylase.
*There is buffering, too, through bicarbonate.
*Amylase is in the secretion to break down carbohydrates.
*Lipase is also released but it is only active in the stomach.
*Lysozyme is also released.
*Antibodies like IgA are released, too, which is common around many openings.
*Last point.

=====Mucus=====
*Lubrication is one function, also helps cause fecal material to adhere to form a stolid stool.
*Along the GI tract we need to protect the underlying epithelium, so it is interesting that the mucus helps to protect the epithelia.
*The mucus creates a physical barrier to the epithelia and also generates a microenvironment.
*Bicarbonate is found in the mucus, so we call this the neutralizing barrier.

=====Fluids=====
*We secrete about 10L of liquids into the GI tract but only excrete 100 ml / day b/c the intestine is good at reabsorbing.

=====Mumps=====
*Caused by RNA virus.
*Gets into salivary gland such that there is a huge swelling on the side of the neck.
*Can cause sterility in males through epididymysis.
*Unilateral paratoid gland swelling is generally caused by obstruction like a tumor.

=====Teeth=====
*Gingevitis is an infection of the gingeval tissue (the gum line), caused by a bacteria.  Generally contributed to plaque which encourages the build up of bacteria because plaque is a biofilm (a place where bacteria can grow and hide from antibiotics).
**Biofilms are also seen in bladder infections.
*Abscessess

====Pharynx====
*Divided into regions: nasal pharynx (connects GI and respiratory), oral pharynx (connects with bottom of pharynx), laryngopharynx (connects to esophagus).
*In swallowing, the soft pallate has to elevate to block off nasopharynx.  AAnd the epiglottis must come down to block trachea.
*Then bolus moves to the back of the tongue / mouth where it is '''involuntarily''' swallowed.

====Esophagus====
*Connects pharynx to stomach.
*Has sphincter muscles: circular smooth muscles tha thelp open and close openings.
**Some skeletal, some smooth.
*Air in the system causes noises.

=====Barrett's esophagus=====
*Can cause serious problems.
*1% of the population.
*Reflux is coming back from the stomach.
*Acid causes irritation.
*In severe cases, epithelum of the esophagus will take on a new, more gastric-like epithelial state.
**Not clear why, but thought to be a protective response because gastric cells can withstand acid environment more easily.
*1-5% of patients will get esophageal cancer.

=====Acid reflux disease=====
*The cardiac sphincter fails to remain tightly closed such that stomach contents can go back into the esophagus.

=====Hiatal hernia=====
*Can live with this if not too severe.
*A portion of the stomach protrudes back through the diaphram into the hiatus yielding a hernia.

====Stomach====

=====Functions=====
*Storage of food.
*Mechanical breakdown of food.
*Chemical breakdown via HCl.
*Enzymatic break down via salivary lipase and pepsin.
**Pepsin breaks down connective tissue.
*Production of intrinsic factors
**Stimulates absorption of B12.
**I think he called this an endocrine function.

=====Anatomy=====
*Rugae are the pleats that allow for expansion from 50-100mL area.
*In the body of the stomach we have gastric pits.
**Lined by different types of pits that contribute to gastric secretions.
**Two types of cells, primarily: chief cells and parietal cells.
**Chief cells are responsible for secreting pepsinogen (inactive).
**Parietal cells secrete HCl and intrinsic factor.
*How does the pepsinogen get from in the pit into the lumen without getting digested by HCl?
**Because of a process called "fingering".
*Infants secrete rennin which coagulates milk proteins and allows them to digest some fat in the stomach.

=====HCl secretion=====
*This is an active process, so we're physically moving H+ ions from the blood and putting them in the lumen.
*At the same time we're moving HCO3 into the blood.
*This process is moved by NaK atpase and requires the bicarb / Cl cotransporter.
**Exchanged from blood into cell to maintain balance (HCO3 into blood).
*Carbonanic anyhdrase is found in the epithelial cells.
*As before, the H+ is coming from the conversion of Co2 and H20 into Hc03 and H via CA and chance.
 Does K+ move?

=====Gastric fingering=====
*The acid shoots up and through the mucus layer to end up in the lumen of the stomach.
*If some of the acid lands on the mucus gel in contact with the epithelial surface, it will be neutralized by the bicarbonate that is held close to the epithelial cells.  This is why we care about the chemical microenvironment.

=====pH of stomach=====
*Varies by time of day and meals.
*Most acidic between meals.
*As you eat, it changes the composition of the lumen, causing the pH to rise.
*There is also a change in the amount of somatostatin that is released.  It affects gastrin secretion.  Gastrin secretion affects HCl release.

=====Enterooendocrine cells=====
*G cells secrete gastrin
**stimulates HCl secretion, pepsinogen synthesis and muscle contractions.
*D cells secrete somatostatin
**This inhibits gastrin secretion and thus impacts the amount of HCl produced and released.
*The nervous system can affect these cells as can the consumption of food.

=====Involuntary protein spills=====
*These are severe vomiting spells.
*Tooth enamal erosion can occur.
*Can cause alkylosis and dehydration.
*Zollinger-Ellison syndrome
**Tumor of duodenom
**Can cause overproduction of gastrin and HCl causing a very acidic stomach.
*Several brain stem areas control vomitting.
**Feedback to the vomitting center occurs from the intestine, the stomach, the pharynx, and esophagus.
**The outward signals go to the abdominal muscles and diaphragm because we squeeze the stomach.
*The signal to induce this is reverse peristalsis, that is, reverse peristalsis.
**Irritation of the stomach and duodenum can cause this reversal of peristalsis which will move food backward until the stomach is distended and stomach is squeezed.
**Not unusual for bile to be in the vomit.
*The chemoreceptor trigger zone is found in the fourth ventrical (base of cerebellum) is also involved in vomitting.
**Can be stimulatee by electrical or chemica signals.
**Electrical signals come from motion sickness (sent from ears).
**Chemicals like drugs (morphine) can directly stimulate the chemorecptor trigger zone.

=====Pyloric problems affecting infants=====
*Pylormic spasms:
**If the pyloric sphincter doesn't relax, the stomach becomes distended and the baby has to remove food via projectile vomitting.
**Routine projectile vomitting indicates a blockage.

=====Hormones involved in digestion======
*CCK = cholecystokinin
*Secretin
*One other

====Regulation of gastric activity====
*Cephalic phase: prepares stomach to receive food.
*Gastric phase: while food is in stomach.
*Intestinal phase: getting rid of food

=====Gastric secretion: Cephalic phase=====
*Nerves tell G cells of the stomach to release HCl.
*Negative nerves activit on D cells causes release of gastrin.

=====Gastric secretion: Gastric phase=====
*Stretching causes feedback such that....?
*Protein begins to break down which stimulates G cells to produce gastrin.
*Gastrin feeds back to increase HCl production.
*The D cell is released from inhibition such that they stimulate (via gastrin) G cells to release HCl.

=====Gastric secretion: Intestinal phase=====
*Breakdown of carbs stimulates cells of intestine to release hormones.
*This feeds back on chief and parietal cells in the stomach to turn off whatever they produce.

====Digestion in the stomach====
*10-20% of the protein is broken down.
**Most protein being broken down by pepsin is the connective tissue.
*Some carb breakdown occurs via salivary amylase until it gets deactivated by pH.

=====Absorption in the stomach=====
*Lipids can be absorbed.
*Alcohol can be converted to acetaldehyd bye alcohol dehydrogenase.
**Acetaldehyde is poisonous!
*Alcohol is continuously absorbed in the stomach.  This explains the delay of blood alcohol level and stomach alcohol level.
*Most fat absorbed in the duodenum.

*stopped here on 04/19/10.
*started here on 04/21/10.

=====Food propulsion and mixing=====
*One of the main ideas is peristolis which is facilitated by smooth muscle contraction, some segmented, some in waves.
*Essentially, the pyloric sphincter opens to let some of the chyme into the small intestine.
*There are two different environments in the stomach: more liquid and thicker.
**By way of the muscle contractions, the lighter fluid will come into contact with the sphincter.  This causes a stirrinig that keeps the solid material on the inside and the liquid will get dumped ito the duodenom
*Not everything moves through the stomach at the same rate.
**Carbs 3ish hours; protein about 6 hours.  Recall that lipids aren't really digested in the stomach.

=====Peptic ulcers=====
*Ulcers are one of the diseases of this area of the stomach.
*It is a bacterial infection.
*It interferes with the mucosal layer including the bicarbonate barrier.
*This exposes the stomach lining to the acid and degrades the epithelium.
*This generates ulcers in several locations: cardiac end, pyloric end (more common), and even in the duodenom.  So ulcers aren't usually in a particular area.
*Caused by pylori bacteria.

=====Other contributing issues=====
*Smoking stimulates secretion of gastric material like HCl.
*Alcohol leads to breakdown of mucosal barrier.
*Aspirin and NSAIDS breakdown barrier.
**Bits make it really far down into the intestinal tract, actually.  And it can generate ulcers way down in the intestine.

===After the stomach===

====Hepatic protal system====
*As we get down into the intestines, the circulation is set up such that the material is absorbed and taken directly to the liver via the portal system.
*The only exception is the breakdown of fats.
**Short chains, carbon chains of 16 or less, will go into the blood stream to bind with albumin.
*Fatty acids and glycerides and such go straight into the portal system
*Splanchnic circulation = hepatic portal system.
*Through this system, the liver absorbs the majority of the stuff we absorb and reprocesses.

====Liver, gall bladder, duodenom connections====
*Liver, gall bladder, and pancreas are all in contact with the duodenum.

====Liver====
*Liver has four lobes with further divisions into lobules.
*Each lobule has a specific blood supply: artery and vein, and a lymphatic drainage route, too.
*There is an hexagonal pattern to the lobules.
**The corners have the blood flow and the bile duct which runs to the gall bladder.

=====Lobule organization=====
*Here we have sinusoidal capillaries which are leaky.  The openings are very important.  The spaces allow for nutrients to be absorbed by the hepatocytes.  This is the important part of the sinusoidal capillaries in the lobule.
*We also have kupffer cells which are like macrophages and help keep bacteria in check.
*Hepatocytes make bile which is passed down to be stored in the gall bladder.
**So if you take out the gall bladder, the patient will have trouble braeking down fats because they don't have much stored up (only what is in the ducts).
*The liver is also used for storage.
*Toxins in the blood are purified out by the liver.
**Alcohol, ammonia, etc.
*Hepatocytes also generate some blood components like albumin, lipoproteins, clotting factors, and angiotensinogen.

=====Bile=====
*1 liter per day is made.
*It is alkaline.
*So bile comes in just as the acidic content of the stomach is dumped into the duodenum.
*Bile contains salts and acids.  these help in physical breakdown of fat droplets but also help us with ....?
*The gall bladder dehydrates the bile it stores which causes it to be more concentrated than the bile in the lobules.

====Stimulation of the gall bladder====
*Small intestine releases CCK when fat enters the duodenum and triggers release of CCK.
 Missed some stuff here.
*Liver is involved in secreting secretin which is important in bicarb production.
*Bile is highly conserved, as it passes through the intestine about 95% is reabsorbed.
**So we have to generate new bile salts, so we require a cholesterol level to be maintained.
**So why fiber in the diet?  It helps move the lipid biproducts (like cholesterol) out of the GI tract which means that the body will "draw down on" its cholesterol levels.
**As cholesterol precipitates out we generate gall stones.  Can be passed, can use sonification, too.
**Bottom line: gall stones come from too-concentrated bile.

====Jaundice====
*The primary reason in infants is bilirubin buildup as the result of blood cell breakdown.\
 I thought it was because of an underdeveloped liver?
*Hepatic jaundice
*Extrahepatic jaundice, some blockage by gallstones, or cancers or something.

====Cellular structures of pancrease====
*Acini cells genreate one set of compounds and the ducts another.
*Ducts: bicarb; acini cells, enzymes for pancreatic secretions.
*Pancreatic secretions are a "complete mixture".
**Anything we haven't broken down at this point must be broken down by the enzymes of the pancrease or by ...?

=====Secretions of the acini cells=====
*Enzymes in pancreatic secretions contains all the enzymes we need for each type of molecule.

====Stimulus of pancreas====
*Secretin stimulates pancreas.
*HCl in the chyme is responsible stimulating release of secretin by intestinal cells.
*CCK also has an effect.
*Overall, most enzymes are released because of pancreatic activities.

====Pancreatic problems====
*Pancreatitis
*Really painful
*Idiopathic

====Pancreatic cancer====
*4th most common cancer in the US.
*Generally over 50 and more frequent in males
*Usually when you find it you're too late.
*Very rare to treat; fatality rate is 95%.
*Removing the pancreas has its own problems with circulation and digestion; so it isn't easy.

====Intestingal fluid and electrolyte movement====
*Most digestion occurs in the duodenom (the digestive part).
*The rest is all about absorption.
*The SI is a major area for water reasorption with Na and K.
*We secrete some bicarb.
*Large intestine is the fine tuning of water reclaiming and secretion of K and bicarb.

====Small intestine====
*Duodenum (shortest), Jejunum, ilium.

====Intestinal secretion====
*The chloride ion is the ion responsible for fluid secretion.
*Na and bicarb are also secreted.
*CFTR is the transporter so CF affects the intestine.
*There is hypertonic material coming from the stomach (so it wants to draw water into the lumen) and  <the second force that is drawing water from blood into lumen>.
*The small intestine is highly pleated and has lots of microvilli.
*There are glands associated with the intestine: the duodenal glands.
**One thing secreted is mucus and we've talked about the need for that.
*There is also hormone production (urogastrone).  It is is important in regulating the overall level of intestinal secretions.
**Found in urine, found in gastrotract.
*Lymphoid nodules of the intestinal tract.
**Peyer's patches are the immune environment that respondes to anything that leaves the GI tract.

====Small intestine wall====
*The many microvilli generate a brush boarder.
*There are also goblet cells.
*Within the folds we also have papillae which are the extension of the lymphatic and circulatory systems up into the folds.
*Note that this papillae structure generates a countercurrent structure.
**This isn't necessarily good because some oxygen that is in the arterial side gets moved straight into the venous side.
**So in some disease states we cannot meet the oxygen demands at the very tip of the papillae.

====Movements of nutrients in the SI====
*Peristalsis is a unified contraction of smooth muscle.
*It can occur in several forms.
*It can occur on a constant period such that there are segments that mixe the food up nicely thus increasing exposure to enzymes.

====Protein digestion====
*Though previously broken down, too, the final breakdown occurs in the intestine.
*Here we're trying to absorb the protein.
*They have to be broken down in AAs before going into the blood stream, but they can be absorbed from the GI tract in 3 or 4 aa peptides.
*In fact, immune reactions can occur when a peptide gets into the blood.

====Lipids====
*The liver produces bile which helps with emulsification (suspension of fat droplet in water; break large droplet into smaller ones).
*Think dish soap commercial.
*The other piece of the puzzele is colipase which is activated by trypsin such that the lipase can bind and interact with the micell and then break the fats down into three things (short chain fatty acids, amino acis, ?).
*These materials get absorbed by the epithelial cells which either use it or put it into the blood or put it into chilomicron (or something like that).
**Don't eat just before giving blood because chilomicron will be high.

====Lipoproteins and lipid transport====
*HDL, LDL.
*Depositing cholesterol = bad, getting rid of cholesterol = good.
*HDL is able to pick up cholesterol and remove it from the environment.
*LDL will donate cholesterol for deposition throughout the body.

====Carbohydrate digestion====
*This is actually finished in the cells associated with the brushboarder.
*Material coming into the intestine is in three groups: sucrose, lactose, or maltose (ore some polymer of these).
*Sucrase, lactose, and maltase and alpha dextrinase are there to break these down.
*So glucose, galactose, and fructose are what actually gets taken into the cells.
*There is an active transport process to get them into the cells from the lumen and then from the cell into the blood.  This is Na coupled.
**Note that we are taking glucose up the concentration gradient.

=====Problems=====
*Celiac disease.
*Gluten is an additive in baked products; gives texture.
*Immune response to gluten.
*There are irritation and circulation issues.

=====Lactose intolerance=====
*Lactase deficiency.
*Not initially an issue but this is a good place for bacteria to grow and cause gas and other problems like diarrhea.

====Large intestine====
*Secum (appendix).
**We weren't sure what it does but we now know that it and the appendix probably harbor cells that help activate the immune system.
*Then move on to the colon and rectom.
*Distension of the rectum stimulates deficationt.
*Mostly just secretion, not much digestion.
*We do have some good activity going on because of bacteria, though, which give us our vitamin K.
*there is some Na absorption along with Cl.  This is aldosterone controled.
*Bicarb and Chloride are exchanged (bicarb out) in order to keep the ion balance.
**This causes some obligatory water absorption to maintain osmolality.
*800 species of bacteria in our colon.
**Take care of vitamin synthesis.
**Help with protein breakdown to amino acids.
**Help breakdown bilirubin which gives tool its color.
**Bacteria generate gas, too.  ABout 500 ml / day.
**We're looking for ways to reduce cow flatulance through diet.

====Osmotic diarrhea====
*We have several types.
*Osmotic diarrhea
**When something causes water to be secreted and not reabsorbed.
**One example is lactose intolerance, or infection and inflammation.  
**It is something in the digestive tract proper.

====Secretory====
*Something is secreted into the luman dand water is following.
**Chloride is the main ion.
**cholera toxin can cause this because it constitutively activates chlorid secretion.
***Can cause 20 l / day to move through the tract.
***So we ahve to think about maintaining ion composition and water when treating diarrhea.

====Motility disorder diarrhea====
*We can have diarrhea if we aren't moving food as we should.
*Too fast = diarrhea, too slow = constipation.

====Inflammation====
*Generally this type of problem comes with other issues like fever and abdominal pain or blood in the stool.

====Constipation====
*Water retention.
*WAter mobility decrease, fiber issues (fiber helps take chol out of the system so liver uses excess chol to produce bile salts and ythus reduce circulating levels).

====Defecation reflex====
*As rectum is distended, it sends a reflex response that cuases sphincter to relax.
*At some point the pressure builds up enough that voluntary inhibition cannot inhibit the sphincter.
*You can't train kids before they are able to voluntarily control if they physiologically can't control the sphincter.
*Strethc of rectom causes signal then reflexes back down to cause contraction of surrounding muscles such that poop comes out.

====Aging====
*The blood supply changes so absorption changes.
*Motility will become an issue so absorption and secretion will be different.
*Flavors and smells will decrease.
*Cancers increase.

*Gastric bypass skips the duodenum so we have less time to digest and resorb and thus reduce caloric intake.

*stopped here on 04/21/10.