Chapter 23: Digestive System Flashcards
Digestive Tract:
o About 9 meters or 30 feet long (in cadaver).
o Accessory organs: Teeth, Tongue, Salivary glands, Liver, Gall bladder, Pancreas.
o Most of “stuff” inside tube has not yet entered body tissues!
Nutrient Disassembly:
o Carbohydrates become monosaccharides (Glucose, Fructose, Galactose).
o Triglycerides become Fatty acids + glycerol, some monoglycerides.
o Proteins become amino acids (few di- and tri- peptides).
o Vitamins stay as vitamins.
o Minerals stay as minerals.
o Water stays as water.
Processes of Digestive System:
o Ingestion. o Mechanical Digestion (mixing). o Chewing = Mastication. o Propulsion: o Deglutition = swallowing. o Peristalsis. o Mass movements. o Secretion (water, mucus, bile, enzymes, hormones). o Chemical Digestion = breaking nutrients down into small pieces. o Absorption (small intestine). o Defecation.
Histology of the Digestive Tract:
o 4 Tunics (Layers): Mucosa, Submucosa, Muscularis Externa, and Serosa.
Mucosa:
o Mucous epithelium: o Many types. o Exocrine cells. o Endocrine cells. o Lamina propria: o Very vascular!! o Lymphatic follicles. o Glands. o Muscularis mucosae.
Submucosa:
o Thick c.t. layer. o Bigger blood and lymphatic vessels. o Glands. o Lymphatic follicles. o Submucosal plexus (Meissner’s plexus).
ENS (Enteric Nervous System):
o Nervous network regulating digestive motility, secretions, and blood flow
o More neurons than spinal cord!
o Definitely influenced by ANS:
o Parasympathetic:
o Enhances gland secretion.
o Enhances motility.
o Sympathetic:
o Inhibits gland secretions.
o Inhibits smooth muscle contraction (exception: some sphincters are excited by sympathetic nerv. system).
o Causes vasoconstriction of blood vessels to the digestive tract.
Regulation of Digestive System:
o Local neuronal control: o Enteric sensory neurons (detect stretch & chemicals). o Enteric motor neurons (activate glands or change motility). o CNS control: o ANS: vagus and sympathetic control. o Conscious sight/smell/taste. o Hormonal control: o Systemic (gastrin, CCK, secretin). o Paracrine (histamine, PGs).
Muscularis Externa:
o Circular layer of smooth muscle. o Can form sphincters! o Myenteric (Auerbach) plexus. o Longitudinal layer of smooth muscle. o Exceptions.
Peristalsis:
o Adjacent segments of alimentary tract organs alternately contract and relax moving food along the tract distally.
Serosa:
o Outermost layer.
o Usually represents visceral peritoneum.
o Sometimes not part of peritoneum = adventitia.
Peritoneum:
o Largest serous membrane of body.
o Visceral peritoneum.
o Peritoneal cavity.
o Parietal peritoneum.
o Mesentery = double layer of peritoneum that stabilizes intestines/keeps them from becoming entangled during digestion.
o Examples: Mesentary “proper”, mesocolons, lesser omentum, greater omentum, and falciform ligament.
Retroperitoneal Organs:
o Intraperitoneal: organ is almost completely surrounded by peritoneum.
o Retroperitoneal: lies against the posterior body wall and is covered by peritoneum only on the anterior side:
o Examples: Duodenum, Pancreas, Ascending and descending colon, Rectum, Kidneys, ureters, urinary bladder and Adrenal glands.
Blood Supply of the Digestive System:
o Arteries: o Celiac trunk o Superior mesenteric a. o Inferior mesenteric a. o Veins from pancreas, stomach, GB, spleen, small and large intestines drain into the HEPATIC PORTAL VEIN. o Hepatic portal system.
Tongue:
o Skeletal muscle. o Lingual papillae: o Filiform. o Fungiform. o Foliate. o Circumvallate. o Lingual tonsils. o Lingual glands: o Mucus and lingual lipase.
Salivary Glands:
o Parotid: below ear/over masseter muscle.
o Submandibular: lower edge of mandible.
o Sublingual: deep to tongue in mouth floor.
o All have ducts emptying into oral cavity.
o Secrete salivary amylase, lysozyme, IgA.
Functions of Saliva:
o Deglutition: Swallowing. o Taste. o Buffer. o Chemical digestion. o Salivary amylase. o Protection: o Lysozyme enzyme. o IgA. o Rinsing action—1 to 1.5 quarts/day!!!
Tooth Composition:
o Enamel: o Calcium phosphate or carbonate. o Hardest substance in the body. o Dentin = calcified c.t. that is harder than bone! o Cementum: o Bone-like. o Attaches root to periodontal ligament.
Dentition:
o Primary = deciduous = baby teeth:
o 20 teeth that start erupting at 6 months.
o Permanent teeth:
o 32 teeth that erupt between 6 to 12 years.
o Differing structures indicate function.
o Incisors for biting.
o Canines for tearing.
o Premolars and molars to crush/grind.
Pharynx:
o Skeletal muscle lined by mucous membrane.
o DEGLUTITION pushes bolus of food into oropharynx.
o Soft palate elevated.
o Larynx lifted as epiglottis closes.
Digestive Processes of Esophagus:
o 1. Buccal Phase: The upper esophageal sphincter is contracted (closed). The tongue presses against the hard palate forcing the food bolus into the oropharynx.
o 2. Pharyngeal-esophageal phase begins: The tongue blocks the mouth. The soft palate and its uvula rise, closing off the nasopharynx. The larynx rises so that the epiglottis blocks the trachea. The upper esophageal sphincter relaxes; food enters the esophagus.
o 3. Pharyngeal-esophageal phase continues: The constrictor muscles of the pharynx contract, forcing food into the esophagus inferiorly. The upper esophageal sphincter contracts after food enters.
o 4. Peristalsis moves food through the esophagus to the stomach.
o 5. The gastroesophageal sphincter surrounding the cardial orifice opens. After the food enters the stomach, the sphincter closes, preventing regurgitation.
Esophageal Disorders:
o Dysphagia: difficult swallowing.
o Esophageal obstructions (tumors, constrictions).
o Impaired peristalsis (neuromuscular disorders).
o Acute esophagitis: ingestion of irritating substances, viral inflammation, intubation.
o Barrett’s esophagus (dysplasia).
o GERD = gastroesophageal reflux disease.
o LES fails to close adequately.
o Stomach contents “reflux”.
o HCl from stomach irritates esophageal lining = heartburn (radiating substernal pain).
Risk Factors for GERD:
o Hiatal hernia
o Recurrent vomiting (bulimia)
o Lying down right after a meal
o Delayed gastric emptying (common in DM)
o Increased abdominal pressure: Pregnancy or obesity, Tight fitting clothing, Large meals.
o Reduced LES muscle tone: Smoking, OCAs, Pregnancy (or even late menstrual cycle stages), Large amounts of dietary fat, Alcohol and caffeine, Carminatives (peppermint and spearmint).
Hiatal Hernia:
o Protrusion of stomach through the esophageal hiatus of the diaphragm.
o 2 types of Hiatal Hernia:
o Sliding hiatal hernia (95 percent); Very common.
o Paraesophageal.
o Most common GI d/o !!!!!
o LES fails to close adequately →stomach acid “refluxes” leads to irritation esophageal mucosa.
o Causes severe esophagitis due to excessive gastric reflux: GERD.
Gross Anatomy of the Stomach:
o Size:
o 50 mL – 1.5 L
o Regions:
o Cardiac region, Fundus of stomach, Body of stomach, Pyloric region.
o Gastric emptying:
o Solid food has been liquified to chime.
o Pyloric stenosis.
Protection of Stomach Mucosa:
o Thick coat (1 to 3 mm) of alkaline mucus.
o Tight junctions of epithelial cells.
o External membranes of glandular cells are not permeable to HCl.
o Pepsin is secreted in an inactive form (pepsinogen).
o Damaged mucosal cells are SHED every 3 to 6 days.
o Constant balance between acid and mucus.
Peptic Ulcer Disease (PUD):
o Erosion from chronic inflammation.
o 80 percent of peptic ulcers are actually in duodenum.
o 10 percent of US adults will have an ulcer.
o Caused by: Hypersecretion of HCl, hyposecretion of mucus, Helicobacter pylori infection.
Mucosa and Gastric Glands:
o No goblet cells.
o Mucous neck cells.
o Parietal cells— secrete:
o HCl, and Intrinsic factor.
o Chief cells— secrete inactive pepsinogen enzyme (gastric lipase and rennin in infants).
o HCl converts pepsinogen to pepsin (active form).
Parietal Cell Secretion of HCl:
o Stimulus: Ach, Histamine, and Gastrin. (All three are needed)
Parietal Cells:
Secrete Intrinsic Factor:
o B-12 bound to dietary protein in food.
o Pepsin and acid free it from this dietary pro.
o B-12 combines with cobalophilin (a protein from saliva).
o Pancreatic proteases cleave this bond.
o B-12 binds with intrinsic factor.
o Receptor mediated endocytosis in ileum.
Enteroendocrine Cells:
o Gastrin hormone (g cell)
o “get it out of here”
o Target tissue = stomach, LES, ileocecal sphincter, large intestine
o Release more gastric juice
o Increase gastric motility
o Relax pyloric sphincter
o Constrict esophageal sphincter preventing entry
o Histamine: target tissue = parietal cells, which have H-2 receptors.
o Serotonin: target tissue = gastric smooth muscle (contraction).
o Ghrelin: increases appetite.
Chemical Digestion in Stomach:
o Protein digestion begins:
o HCl denatures (unfolds) protein molecules.
o HCl transforms pepsinogen into pepsin that breaks peptides bonds between certain amino acids.
o Rennin = Chymosin, important in kids, enzyme that acts on casein in milk.
o Fat digestion continues:
o Gastric lipase splits the triglycerides in milk fat.
o most effective at pH 5 to 6 (infant stomach).
o HCl lowers stomach pH to 1.5 to 3.5, kills microbes in food and inactivates some natural enzymes found in food.
Absorption in Stomach:
o Alcohol (usually only a little).
o Meals containing large amounts of fat will slow the rate of ETOH absorption.
o ETOH adheres to the fat droplets in chyme!
o Most alcohol absorbed in small intestine.
o Aspirin and some lipid soluble meds.
o Short chain fatty acids.
o Water and electrolytes.
Cephalic Phase:
Stomach Getting Ready
o Cerebral cortex =sight, smell, taste & thoughts of food.
o Stimulate parasympathetic nervous system.
o Vagus nerve:
o Increases stomach muscle and glandular activity.
o Sympathetic N.S.:
o Inhibits stomach activity.
Gastric Phase:
Stomach Working
o Nervous control keeps stomach active.
o Stretch receptors & chemoreceptors provide information.
o Vigorous peristalsis and glandular secretions continue (myenteric and vagal reflexes).
o Chyme is released into the duodenum.
o Endocrine influences over stomach activity
o Distension and presence of caffeine or protein cause G cells to secrete GASTRIN into blood.
o GASTRIN hormone increases stomach glandular secretion.
o GASTRIN hormone increases stomach churning and pyloric sphincter relaxation.
o Histamine and ACh (parasympathetic nervous system) also stimulate gastric secretions (acid).
2 Central Reflexes Triggered by Stimulation of Stretch Receptors in Stomach Wall:
o Gastroenteric Reflex: Stimulates motility and secretion along the entire small intestine.
o Gastroileal Reflex: Triggers the opening of the ileocecal valve, allowing materials to pass from the small intestine into the large intestine.
Intestinal Phase:
Stomach Emptying
o Stretch receptors in duodenum slow stomach activity and increase intestinal activity.
o Distension, fatty acids or sugar signals medulla .
o Sympathetic nerves slow stomach activity.
o Decreased parasympathetic activity (vagus).
o Regulated by hormones from small intestine:
o Secretin hormone decreases stomach secretions.
o Cholecystokinin (CCK) decreases stomach emptying.
o Gastric inhibitory peptide (GIP) (secreted by small intestine) decreases. stomach secretions, motility and emptying.
Liver:
o Largest gland in body; 2nd largest organ, exocrine and an endocrine organ.
o Located just underneath the diaphragm in the upper right quadrant of abdominal cavity.
o Has 4 gross (macroscopic) lobes.
o Right lobe, left lobe (seen anteriorly), divided by the falciform ligament (mesentery).
o Quadrate lobe, caudate lobe (underview).
o Enclosed by thin c.t. capsule, very little c.t. in rest of liver compared to other organs (mainly supportive reticular fibers).
o Almost completely covered by visceral peritoneum.
Porta Hepatis:
o Inferior surface.
o Blood vessels, ducts, nerves, lymph vessels enter/exit the liver.
o Beginning here, the c.t. capsule sends a branching network of SEPTA into the liver, dividing it into hexagon-shaped lobules.
Portal Area (Portal Triad):
o Branch of common hepatic artery.
o Brings in oxygenated blood from aorta.
o Branch of hepatic portal vein.
o Brings in nutrient rich blood from intestines, as well as venous blood from the pancreas and spleen.
o Bile duct receiving bile from canaliculi in liver cells that will eventually form either the right or left hepatic duct.
o Lymphatic vessels.
o Liver produces large quantities of lymph!
Unique Blood Supply to Liver:
o Receives blood from two sources:
o Oxygenated blood from hepatic arteries.
o Venous blood from hepatic portal vein (coming from nutrient -rich venous blood of intestines, as well as the spleen and pancreas).
o Blood “percolates” through hepatic sinusoidal capillaries in between plates of liver cells (VERY leaky).
o Sinusoidal capillaries empty into a central vein at the center of a hepatic lobule.
o Central veins of all hepatic lobules drain eventually into several hepatic veins.
o Hepatic veins drain into inferior vena cava.
Specialized Cells of the Liver:
o Hepatocytes = 80 percent of cells of liver.
o Kupffer cells = fixed macrophages.
o Line hepatic sinusoids.
o Remove and recycle worn out RBCs.
o Attack pathogens and remove debris.
o Endothelial cells lining liver sinusoids.
o Ito cells = stellate shaped cells.
o Store Vitamin A and lipids.
o Acquire features of myofibroblasts with liver injury or liver disease (fibrosis).
Hepatocytes:
o Polyhedral cells, with 6 or more surfaces.
o Form hepatic plates (plates of hepatocytes in-between hepatic sinusoids).
o Round nuclei; 25% of cells binucleate; 50 percent of nuclei are oddly polyploid!!!
o Contain glycogen granules, lipid droplets, thousands of mitochondria, peroxisomes, lots of endoplasmic reticulum.
o MAKE BILE and secrete it into tiny ducts called bile canaliculi.
General Functions of the Liver:
o Production/secretion of bile.
o Excretion of bilirubin/other wastes.
o Phagocytosis by Kupffer cells (helps spleen filter the blood).
o Detoxification of alcohol, meds, hormones.
o Converts NH3 to urea (via ornithine cycle).
o Synthesizes clotting factors and TPO.
o Makes hormones: EPO, TPO, hepcidin, IGFs.
o Helps to activate Vitamin D (makes calcidiol).
o Makes 90 percent of plasma proteins.
o Stores stuff: glycogen, fat, Vit. B-12, iron.
Bile Formation:
o Hepatocytes produce 500 -1000 mL/day.
o Composition:
o Water (mostly) and electrolytes.
o Cholesterol.
o Bile acids (salts of cholesterol byproducts).
o Bilirubin (primarily as bilirubin glucuronide).
o Phospholipids (e.g., lecithin).
o Metabolic byproducts of meds.
o Contains NO digestive enzymes!!!
o Excreted by hepatocytes into bile canaliculi formed between hepatocytes.
Functions of Bile:
o Bile has alkaline pH (7.6 to 8.6); can neutralize acid pH of stomach juices.
o Emulsifies fat (separates it into smaller clumps) which makes it easier to digest.
o Facilitates fat and cholesterol absorption.
o Contains excretory products.
o Bile pigments (e.g., bilirubin).
o Fat-soluble hormones and med by-products.
Enterohepatic Circulation:
o Most bile salts are reabsorbed in the distal ileum (small intestine). o Only 20 percent excreted into feces. o 1. Reabsorbed into intestinal capillaries. o 2. Superior mesenteric vein. o 3. Hepatic portal vein. o 4. Liver sinusoidal capillaries. o 5. Captured by hepatocytes. o 6. Resecreted into new bile.
Metabolic Functions of the Liver:
o The liver gets “first dibs” at nutrient-rich blood coming from recent absorption in the small intestine.
o Liver processes/metabolizes blood-borne nutrients in a multitude of ways:
o Carbohydrate metabolism.
o Lipid metabolism.
o Protein metabolism.
o ETOH metabolism.
Carbohydrate Metabolism:
o Liver is essential for maintaining normal blood glucose levels!!
o Metabolic pathways that increase serum glucose (i.e., between meals):
o Glycogenolysis: converts glycogen to glucose.
o Gluconeogenesis: forms NEW glucose.
o Metabolic pathways that decrease serum glucose (i.e., after a meal):
o Glycogenesis: converts glucose to glycogen.
o Lipogenesis: converts excess carbs to TG (fat).
Lipid Metabolism:
o Liver can make fat (TG) = lipogenesis.
o Liver can store some fat as TG.
o Liver stores fat-soluble vitamins.
o 85 percent of cholesterol in our bodies is made by liver and intestinal cells (only 15 percent comes from our diet).
o Liver synthesizes lipoproteins that carry cholesterol to/from body cells.
o Liver can break down TG into fatty acids (F.A.) to make ATP: lipolysis.
Protein Metabolism:
o Liver deaminates many amino acids (a.a.) = removes the amino group.
o Amino group converted to ammonia (NH3) ,which is toxic, so NH3 is converted to urea (less toxic).
o Liver synthesizes most plasma proteins.
o Liver synthesizes proteins that it needs for itself (e.g., enzymes needed in these biochemical pathways!)
Alcohol Metabolism:
o 80 percent of ETOH is absorbed in small intestine; 20 percent absorbed in stomach.
o Detoxified by a liver enzyme called alcohol dehydrogenase:
o ETOH turns into acetaldehyde.
o High levels of acetaldehyde are toxic:
o Causes inflammation of liver and pancreas.
o Decreases ability to oxidize fatty acids leads to fatty and enlarged liver (hepatomegaly).
o Actually destroys hepatocytes.
Hepatitis:
o Inflammation of the Liver.
o Causes include overconsumption of ETOH, toxic chemicals, pathogens, obesity!
o Viral hepatitis:
o HVA = “infectious” hepatitis (about 30 percent of cases).
o HVB = “serum” hepatitis (about 40 percent).
o HVC = “non-A, non-B” hepatitis (about 20 percent).
o HVD = mutated virus that needs HVB at same time to be infectious.
o HVE = spread enterically like HVA.
o HVF = very little known about this virus.
Cirrhosis:
o Chronic inflammation of liver.
o Death of hepatocytes and replacement by fibrous c.t.
o Fibrous bands of c.t. destroy the normal architecture of the liver—portal hypertension.
o Necrotic cells replaced by regenerative nodules in between the fibrous c.t.
o Causes of cirrhosis:
o Alcoholism.
o Biliary obstruction.
o Chronic and severe hepatitis.
o Non-alcoholic fatty liver dz (NAFLD) (30 percent of US).
Liver Regeneration:
o Liver cells have a remarkable capacity for regeneration in many species, including humans.
o If 60 to 75 percent of the organ is removed in humans, it will completely regenerate to normal size within 4 weeks!!!
o Controlled by transforming growth factor-alpha (TGF-alpha), TGF-beta, hepatopoietin, and other hormones.
Liver Exocrine Function:
Bile into ducts.
Liver Endocrine Function:
Hormones into the blood stream. (TPO, EPO, Angiotensin II).
Gall Bladder:
o Pear-shaped sac on underside of liver.
o Receives, concentrates, and stores bile made in the liver.
o Can hold about 40 to 100 mL of fluid.
o Has a fundus, a body, and a neck leading to the cystic duct.
Cholelithiasis (Gallstones):
o Occurs in 20 percent of women and 8 percent of men over the age of 40.
o Risk factors:
o Estrogen (multiple births and OCAs).
o Obesity.
o Rapid weight loss.
o Disease of the terminal ileum.
o Two types:
o Cholesterol gallstones (75 – 80 percent).
o Pigmented gallstones (20 – 25 percent).
Pancreas:
o Head lies within curve of duodenum, body extends across abdominal cavity, tail lies close to spleen.
o Most of the pancreas is posterior to the stomach.
o Most of the pancreas is retroperitoneal.
o Exocrine Gland and Endocrine Gland.
Endocrine Functions of the Pancreas:
o 1 percent of pancreas = hormone secreting cells arranged in clusters called PANCREATIC ISLETS or ISLETS OF LANGERHANS.
o Pancreatic islets contain different cell populations, each of which secrete specific hormones (e.g., beta cells secrete insulin AND amylin).
o The hormones produced in the pancreatic islets are released into blood (NOT into the pancreatic ducts).
o Pancreas has a rich blood supply!
Hormones Secreted by Islets of Langerhans:
o Alpha cells: glucagon, increases blood glucose.
o Beta cells: insulin, decreases blood glucose.
o Beta cells also secrete AMYLIN!
o D cells: somatostatin causes inhibition secretion of both glucagon and insulin secretion.
Exocrine Functions of the Pancreas:
o 99 percent of pancreas = clusters of glandular epithelial cells called serous acini AND their ducts.
o 1. Serous (pancreatic) acinar cells secrete digestive ENZYMES into pancreatic DUCTS for the chemical digestion of chime.
o 2. The DUCT CELLS leading away from the acinar clusters secrete alkaline juices (pH 7.1-8.2) rich in bicarbonate ions to help neutralize acidic chyme coming from the stomach.
o Pancreas secretes 1200 – 1500 mL of these “pancreatic juices” each day.
Secretions of Serous Acini:
o Acini secrete essential digestive enzymes:
o Pancreatic amylase.
o Pancreatic lipase.
o Nucleic acid digesting enzymes (nucleases):
• Ribonuclease.
• Deoxyribonuclease .
o Pancreatic proteases—most in an inactive (zymogen) form.
o Trypsinogen.
o Chymotrypsinogen.
o Procarboxypeptidase.
o Pancreatic proteases are not activated until they are released into the duodenum.
Pancreatic Alpha-Amylase:
o Carbohydrase.
o An enzyme that breaks down certain starches. Pancreatic alpha-amylase is almost identical to salivary amylase.
Pancreatic Lipase:
Breaks down certain complex lipids, releasing products (such as fatty acids) that can be easily absorbed.
Nucleases:
Break down RNA or DNA.
Proteolytic Enzymes:
o Breaks proteins apart.
o Secreted as inactive proenzymes that become active once they are in the duodenal lumen.
o Include trypsin, chymotrypsin, carboxypeptidase, and elactase.
o Together they break down proteins into a mixture of dipeptides, tripeptides, and amino acids.
6 Steps of Pancreatic Regulation:
o 1. Chyme entering duodenum causes duodenal enteroendocrine cells to release cholecystokinin (CCK) and secretin.
o 2. CCK and secretin enter the bloodstream.
o 3. CCK induces secretion of enzyme-rich pancreatic juice. Secretin causes secretion of HCO3 rich pancreatic juice.
o 4. Bile salts and, to a lesser extent, secretin transported via bloodstream stimulate liver to produce bile more rapidly.
o 5. CCK (via bloodstream) causes gallbladder to contract and hepatopancreatic sphincter to relax. Bile enters duodenum.
o 6. During cephalic and gastric phases, vagal nerve stimulates gallbladder to contract weakly.
Pancreatic Regulation by ANS:
o Parasympathetic nervous system (“rest and digest”):
o Stimulates secretion of bile AND pancreatic juices via the vagus nerve.
o Weak contraction of GB smooth muscle.
o Stimulates secretion of insulin from beta cells of pancreas, even before you start eating!
o Sympathetic nervous system:
o Inhibits secretion of bile AND pancreatic juices.
o Inhibits secretion of insulin from beta cells of pancreas.
Pancreatic Regulation by Hormones:
o Small intestine releases CCK (when stimulated by fats/amino acids arriving from stomach):
o Stimulates bile secretion by exciting smooth muscle in gall bladder to contract and release bile.
o Stimulates pancreatic acinar cells to release digestive enzymes.
o Relaxes Sphincter of Oddi (hepatopancreatic sphincter) to allow secretions to enter duodenum.
o Small intestine releases SECRETIN (when stimulated by acidic chyme from stomach):
o Stimulates pancreatic duct cells to release alkaline juices (bicarbonate ions).
o Stimulates hepatic bile ducts to release bicarb.
o Increases rate of production/secretion of bile.
o Gastrin (released by the stomach and the duodenum):
o Stimulates pancreatic enzyme secretion.
o Stimulates gall bladder contraction.
o Only 50 percent as strong as CCK in these actions.
o Small intestine also releases INCRETINS which stimulate the secretion of insulin (among other things):
o GLP-1 (glucagon-like peptide).
o GIP (glucose-dependent insulinotropic peptide).
o New diabetic meds try to enhance incretins!!
Disorders of Pancreas:
o Pancreatitis o Can be acute or chronic. o Midabdominal pain radiating to back. o Fever, N and V, edema in peritoneal cavity. o Potentially very serious disorder. o Associated with several clinical d/o: o Alcoholism. o Obstructive biliary tract disease (cholelithiasis). o Peptic ulcers. o Hyperlipidemia (outrageous). o Trauma and pathogen infections. o Cause unknown in 10 to 20 percent of causes.
Chronic Pancreatitis Leads to Pancreatic Cancer:
o Chronic pancreatitis:
o Most common cause = chronic alcohol abuse.
o Can lead to insulin-dependent DM.
o Risk factor for pancreatic cancer.
o Pancreatic Cancer:
o 4th cause of cancer death in men; 5th in women.
o Nearly 100 percent mortality.
o Risk Factor = cigarette smoking and chronic pancreatitis; cause usually unknown.
Duodenum:
o C-shaped. o Brunner’s glands: o Alkaline mucus. o pH of 8.2 to 9.3. o Papilla of Vater: o Bile. o Pancreatic enzymes. o Enzymes: o Enteropeptidase o Hormones: o CCK, Secretin, incretins, VIP, even gastrin.
Hormones of Duodenum:
CCK
o Secreted when fats/a.a. arrive from stomach
o Target tissues:
o Gall bladder: contract.
o Pancreatic acinar cells: Increase digestive enzymes.
o Spinhcter of Oddi: relax.
o Stomach: Decrease secretions and Decrease motility.
o Brain: Decrease appetite.
Hormones of Duodenum:
Secretin
o Secreted when acidic chyme arrives from stomach (low pH).
o Target Tissues:
o Pancreatic DUCT cells:
o Secrete alkaline juices, rich in bicarbonate ion.
o Hepatocytes:
o Increase secretion bile.
o Hepatic BILE DUCT cells:
o Secrete alkaline juices, rich in bicarbonate ion.
Hormones of Duodenum:
Misc.
o VIP:
o Vasoactive intestinal peptide.
o Dilates capillaries in intestines.
o Stimulates alkaline secretions of intestinal glands.
o Decreases acid secretions of stomach.
o Gastrin:
o Stimulates gall bladder contraction.
o Stimulates pancreatic enzyme secretion.
o Only 50 percent as strong as CCK(stimulates gastric acid).
Other Hormones from Small Intestine:
Incretins
o Secreted in response to carbs and a.a. from stomach.
o Target tissue:
o Pancreatic islets.
o Stomach.
o GLP-1:
o Stimulates insulin secretion from beta cells of pancreas.
o Inhibits glucagon secretion from alpha cells of pancreas.
o GIP (glucose-dependent insulinotropic peptide):
o Stimulates insulin secretion.
o Inhibits gastric secretions and motility (minor effect).
Jejunum and Ileum:
o Jejunum: o Most absorption of nutrients occurs here. o Spectacular blood supply. o Ileum: o Fine-tuning of absorption. o Absorption of Vit B-12. o Enterohepatic circulation. o Peyer’s patches.
Plicae Circulares (Circular Folds):
o 1 cm tall.
o Permanent ridges.
o Greatest number in jejunum.
o Increase surface area AND cause the chyme to SPIRAL rather than move in a straight line.
Villi:
o 0.5 to 1 mm long, many MANY villi covering the surface of ONE plica circularis. o Lined by 2 cell types: o Simple columnar epithelium. o Goblet cells. o Core of villus = lamina propria. o Capillaries. o Lacteals. o Smooth muscle fibers.
Microvilli:
o 1 micron tall.
o Microvilli are extensions from one cell, typically more than 2500 to 3000 microvilli extending from each intestinal cell!!
o Look like bristles on a brush = the “brush border” or “striated border” under a regular light microscope.
o Contain enzymes to fine-tune chemical digestion.
Surface Area Amplification:
o Plicae circulares: o Increase surface area 2 to 3 fold. o Intestinal villi: o Increase surface area 8 to 10 fold. o Microvilli on each cell: o Increase surface area 400 to 600 fold. o Total surface area = 2200 square feet!
Intestinal Crypt (Crypt of Lieberkuhn):
o Contain intestinal cells that dip below the surface and between the bases of the intestinal villi.
o Contain: Goblet cells, Enteroendocrine cells, Paneth cells, Stem cells.
o Cells are involved in secretion (not much absorption).
o Produce 1-2 liters of intestinal “juice” each day.
o Found in large intestine also.
Digestive Processes of Small Intestine:
o Ingestion (if feeding tube).
o Mechanical digestion:
o Segmentation.
o Propulsion:
o Pushes chyme about 1 cm/minute.
o Secretion
o Chemical Digestion Up to this point, only 10-20% of dietary protein has been digested, less than 10% of lipids, and only a very minor amount of carbohydrates.
o Absorption: 90% will take place in small intestine!
o Defecation (rare–only if ostomy bag starts in distal ileum).
Secretions of Small Intestine:
o 1 to 2 liters of slightly alkaline fluid/day (pH of about 7.6).
o Water, lytes, mucus, very few digestive enzymes.
o Brush border enzymes (not actual secretions—part of plasma membrane of simple columnar cell’s microvilli).
o 6 carb-digesting enzymes: Glucoamylase, Sucrase, Maltase, Alpha-dextrinase, Lactase, Alpha-glucosidase.
o Some peptidases: Aminopeptidase, Dipeptidases.
o Some nucleotide-digesting enzymes.
Chemical Digestion in Small Intestine:
o Small intestine is a “MIXING BOWL” that receives secretions from accessory digestive organs:
o Bile and alkaline juices from the liver.
o Digestive enzymes and alkaline juices from the pancreas.
o It is the PANCREATIC ENZYMES (all the different peptidases, pancreatic amylase, pancreatic lipase) that do MOST of the chemical breakdown into smaller fragments, but the small intestinal brush border enzymes break these fragments into absorbable molecules!
Carb Digestion in Small Intestine:
o Pancreatic amylase breaks down both glycogen and starch into smaller chains of glucose. o Alpha dextrinase and glucoamylase & alpha-glucosidase (brush border enzymes) break these smaller chains (oligosaccharides) into disaccharides. o Disaccharidases (brush border enzymes): o Sucrase: sucrose (table sugar) turns into glucose and fructose. o Lactase: lactose (milk sugar) turns into glucose and galactose. o Maltase: maltose turns into glucose and glucose.
Lactose Intolerance:
o Caused by insufficient LACTASE production by mucosal cells.
o Genetic vs. acute loss of enzyme.
o Undigested lactose in chyme retains fluid in feces.
o Bacterial fermentation of the lactose produces gases .
o Symptoms: bloating, flatulence, diarrhea.
o Treat: avoid foods containing lactose vs. using lactase enzyme tablets.
Carb Absorption in Small Intestine:
o Sodium-glucose transport proteins (SGLT) in membrane help absorb glucose and galactose.
o Fructose absorbed by facilitated diffusion (GLUT-5 transporter).
o All 3 monosaccharides leave intestinal cell by facilitated diffusion using a GLUT2 transporter.
Protein Digestion and Absorption in Small Intestine:
o Pepsin has optimal pH of 1.5 to 3.5; inactivated in duodenum.
o Pancreatic enzymes take over protein digestion by hydrolyzing polypeptides into shorter oligopeptides.
o Brush border enzymes finish task, producing amino acids that are absorbed into intestinal epithelial cells.
o Amino acid cotransporters move a.a. into epithelial cells and facilitated diffusion moves amino acids out into blood stream.
Steps of Protein Digestion and Absorption in Small Intestine:
o 1) Proteins and protein fragments are digested to amino acids by pancreatic proteases(trypsin, chymotrypsin, and carboxy-peptidase) and by brush border enzymes (carboxypeptidase, aminopeptidase, and dipeptidase) of mucosal cells.
o 2) The amino acids are then absorbed by active transport into the absorptive cells, and move to their opposite side.
o 3) The amino acids leave the villus epithelial cell by facilitated diffusion and enter the capillary via intercellular clefts.
Digestion of Lipid in Small Intestine:
o Fats are insoluble in water.
o Bile emulsifies lipids into 1 micron droplets.
o Pancreatic lipase usually removes 2 of the 3 fatty acids from the glycerol, leaving individual F.A. and monoglycerides.
Absorption of Lipids in Small Intestine:
o Short and medium-chain fatty acids (less than 10 to 12 carbons) diffuse through mucosal epithelial cells and into villus capillaries.
o Long chain F.A. (less than 13 carbons), monoglycerides, cholesterol, and Vitamins A, D, E, K diffuse from MICELLES into mucosal epithelial cells.
o Epithelial cells recombine these lipid fragments into a CHYLOMICRON (specific type of lipoprotein).
o Chylomicron leaves epithelial cell by exocytosis, then enters villus LACTEAL.
Composition and Fate of Chylomicrons:
o Composition of Chylomicrons: o 90 percent triglyceride. o 5 percent cholesterol. o 4 percent phospholipid. o 1 percent protein. o Fate: o Enter lacteals to cisterna chili to thoracic duct to left subclavian vein. o Within 10 minutes, half of the chylomicrons have been removed from the blood as they pass by capillary beds serving adipose tissue, skeletal muscle, and the liver.
Absorption of Vitamins in Digestive Tract:
o Fat-soluble vitamins (A, D, E, K):
o Travel in micelles & are absorbed by simple diffusion.
o Water-soluble vitamins (C & B vitamins):
o Absorbed by active/passive transporters.
o Vit B12 combines with intrinsic factor before it is transported into the cells:
o Receptor-mediated endocytosis.
o Absorption does decrease with age (increased risk of pernicious anemia).
o Vit B-12 is absorbed in the distal ileum.
Absorption of Minerals (Electrolytes) in Digestive Tract:
o Lytes enter epithelial cells by diffusion and active transport:
o Sodium co-transported with sugars and a.a.
o Chloride, iodide and nitrate = passively follow.
o POTASSIUM typically absorbed by simple diffusion or facilitated diffusion once water is absorbed.
o If water is not absorbed (diarrhea), then K+ absorption is hinderedà HYPOKALEMIA.
o Hormone-facilitated absorption: (regulated!)
o Calcium, phosphate, magnesium (calcitriol).
o Iron (hepcidin).
Absorption of Water in Digestive Tract:
o About 9 liters of fluid dumped into GI tract each day.
o About 8 liters absorbed in small intestine each day.
o 90 Percent of last liter absorbed by large intestine.
o Water is absorbed by osmosis (following the absorption of salts and organic nutrients) through cell walls into vascular capillaries inside the lamina propria of villi.
Disorders of Small Intestine:
o Ileus:
o Digestive tract movements STOPS.
o Lyte imbalances or blockage of parasympathetic activity by meds.
o Enteritis:
o Any inflammatory process of intestines.
o Infection vs. chemical irritation vs. disease.
o PUD: 80 Percent in duodenum and 20 Percent in stomach.
o Malabsorption syndromes: Multiple etiologies, often present with diarrhea.
Diarrhea:
o Increase in Volume of stool, increase in number of stools per day, or decrease in solid consistency of stool.
o Normally 1 percent of the stool is water.
o 3 Types: Osmotic, Secretory, and Increased Motility.
Cecum and Vermiform Appendix:
o Entrance of chyme into cecum is regulated via the ileocecal valve.
o Gastroilial reflex.
o Vermiform appendix
o About 3” long, narrow lumen, Dense lymphocyte population, Peyer’s patches, Appendicitis.
Appendicitis:
o Inflammation of the appendix due to blockage of the lumen by chyme, foreign body, carcinoma, stenosis, or kinking.
o Symptoms:
o High fever, elevated WBC count, neutrophil count above 75 percent.
o Referred pain, anorexia, nausea and vomiting.
o Pain localizes in right lower quadrant.
o Infection may progress to gangrene and perforation within 24 to 36 hours.
Histology of the Colon:
o Mucosa is much smoother, with no plicae circulares and no villi.
o Intestinal glands (in intestinal crypts) are primarily mucus-secreting cells.
o Thinner wall than small intestine.
o Longitudinal muscle layer of muscularis externa is modified to 3 bands: teniae coli.
o Same general cell types as in small intestine, but more goblet cells and fewer “everything else.”
o Lifespan of surface absorptive cells and goblet cells is about 7 days; replaced by stem cells in the depths of the Crypts of Lieberkuhn (intestinal crypts).
Functions of the Large Intestine:
o Absorption of water and electrolytes:
o Feces are semisolid once they reach transverse colon.
o Secretion of mucus and bicarbonate ions to minimize damage to intestinal wall.
o Absorption of important vitamins made or liberated by bacterial flora of intestinal tract. Vitamin K, Biotin (a B vitamin).
o Concentration, storage and elimination of feces (defecation).
o There are no digestive enzymes released in the large intestine (except by bacteria)!
Normal Bacterial Flora:
o Ferment some indigestible carbohydrate (e.g., cellulose).
o Convert bilirubin into simpler substances that produce color.
o Keep pathogenic bacteria in check.
o Make vitamins.
o Release irritating acids and flatus: Dimethyl sulfide and H2S (stinky), Methane (CH4), H2, N2, CO2, Amines (indoles and skatoles)(stinky).
o Make up 30 percent of dry weight of feces!!
Composition of Feces:
o Water and inorganic salts.
o Sloughed off epithelial cells.
o Bacteria.
o Unabsorbed materials (could not be chemically digested/absorbed):
o Insoluble fibers: Cellulose, lignins; speed up motility and contributes to bulk of stool.
o Soluble fibers: Pectins, gels; slow motility and bind bile salts.
Steps of Defecation:
o 1) Feces move into and distend the rectum, stimulating stretch receptors there. The receptors transmit signals along afferent fibers to spinal cord neurons.
o 2) A spinal reflex is initiated in which parasympathetic motor (efferent) fibers stimulate contraction of the rectum and sigmoid colon, and relaxation of the internal anal sphincter.
o 3) If it is convenient to defecate, voluntary motor neurons are inhibited, allowing the external anal sphincter to relax so feces may pass.
Disorders of Large Intestine:
o Appendicitis: 500,000 cases/year US o Diarrhea. o Constipation = infrequent or difficult defecation. o Inadequate water intake (dehydration). o Decrease in intestinal motility. o Excessive water absorption. o Lack of exercise. o Stress and sympathetic stimulation. o Meds (e.g., codeine, morphine). o Diverticulosis: Herniation of “pouches” of colon through circular muscle of muscularis externa that is NOT supported by teniae coli. o Inflammatory bowel disease (IBD): o Ulcerative colitis. o Crohn’s disease. o Colorectal cancer.
Crohn’s Disease (Regional Enteritis):
o Chronic inflammatory process of ANY part of digestive tract, but most common in ileocecal area.
o Inflammation extends from mucosa, thru submucosa, muscularis externa and serosa.
o Ulcerations and fistulas.
o Thickened intestinal wall constricts lumen.
Inflammatory Bowel Disease (Ulcerative Colitis):
o Inflammation of MUCOSA of the colon and rectum.
o Usually accompanied by rectal bleeding.
o Diarrhea, abdominal pain, fatigue, malaise.
o Abnormal immune response; Sometimes hereditary.
Colorectal Cancer:
o Third most common cancer in US.
o Risk Factors: (HINT: important to remember!)
o Genetics (especially acquired mutations of the p53 tumor suppressor gene).
o Diets high in saturated fat, red meat and alcohol.
o Polyps = Adenomas = Adenomatous polyp (benign mucosal tumors), 10 years to change.
o Familial adenomatous polyposis (FAP).
o Chronic inflammatory diseases.
Screening for Colorectal Cancer:
o Normal blood work:
o Unexplained iron deficiency anemia.
o Fecal occult blood:
o Check stools for presence of blood.
o Flexible sigmoidoscopy + barium enema:
o 50 percent of cancers located between rectum & splenic flexure of colon, esp. sigmoid colon.
o Colonoscopy:
o Remove polyps.
o Recommended for everyone over the age of 50 years.
o 90 percent 5-yr survival if caught at Stage 1 vs. 5 percent survival if found at Stage 4.
