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The Digestive System Digestive System: Overview • The alimentary canal or gastrointestinal (GI) tract digests and absorbs food • Alimentary canal – mouth, pharynx, esophagus, stomach, small intestine, and large intestine • Accessory digestive organs – teeth, tongue, gallbladder, salivary glands, liver, and pancreas Digestive System: Overview Alimentary canal Accessory digestive organs Digestive Process • The GI tract is a “disassembly” line – • Nutrients become more available to the body in each step There are six essential activities: 1. 2. 3. 4. 5. 6. Ingestion Propulsion Mechanical digestion Chemical digestion Absorption Defecation Digestive Process GI Tract • The GI tract is controlled at three levels: 1. Mechanical and chemical stimuli 2. Extrinsic control by CNS centers 3. Intrinsic control by local centers 1. Mechanical and chemical stimuli • Mechano- and chemoreceptors respond to: – Stretch, osmolarity, and pH – Presence of substrate, and end products of digestion • They initiate reflexes that: – Activate or inhibit digestive glands – Mix lumen contents and move them along 2. Extrinsic and 3. Intrinsic Controls • 2. Extrinsic controls – Long reflexes arising within or outside the GI tract – Involve CNS centers and extrinsic autonomic nerves • 3. Intrinsic controls – Nerve plexuses near the GI tract initiate short reflexes – Short reflexes are mediated by local enteric plexuses (gut brain) Enteric Nervous System • Composed of two major intrinsic nerve plexuses that control glands (submucosal) and mobility (myenteric). • Segmentation and peristalsis are largely automatic involving local reflex arcs • Linked to the CNS via long autonomic reflex arc Pathology: Colic • What causes colic? No one is really sure, but there are a few suspected causes, such as intestinal gas, food sensitivity or allergy, or an immature nervous system. Peritoneum and Peritoneal Cavity • Peritoneum – serous membrane of the abdominal cavity – Visceral – covers external surface of most digestive organs – Parietal – lines the body wall • Peritoneal cavity – Lubricates digestive organs – Allows them to slide across one another Peritoneum and Peritoneal Cavity • Peritoneum – serous membrane of the abdominal cavity – Visceral – covers external surface of most digestive organs – Parietal – lines the body wall • Peritoneal cavity – Lubricates digestive organs – Allows them to slide across one another Peritoneum and Peritoneal Cavity • Mesentery – double layer of peritoneum that provides: – Vascular and nerve supplies to the viscera – A means to hold digestive organs in place and store fat • Peritoneal organs (intraperitoneal) – organs surrounded by peritoneum • Retroperitoneal organs – organs outside the peritoneum Pathology: Peritonitis • Inflammation of the peritoneum. Pathology: Hernia • A hernia is a protrusion of a tissue, structure, or part of an organ through the muscular tissue or the membrane by which it is normally contained. The hernia has three parts: the orifice through which it herniates, the hernial sac, and its contents. Histology of the Alimentary Canal • From esophagus to the anal canal the walls of the GI tract have the same four tunics – From the lumen outward they are the 1. 2. 3. 4. • Mucosa Submucosa Muscularis externa Serosa Each tunic has a predominant tissue type and a specific digestive function Histology of the Alimentary Canal Mucosa: Other Sublayers • Mucosa: Moist epithelial layer that lines the lumen of the alimentary canal 1. Secretion of mucus 2. Absorption of the end products 3. Protection against invaders • Submucosa – dense connective tissue containing elastic fibers, blood and lymphatic vessels, lymph nodes, and nerves • Muscularis externa – responsible for segmentation and peristalsis • Serosa – the protective visceral peritoneum Mucosa: Other Sublayers • Mucosa: Moist epithelial layer that lines the lumen of the alimentary canal 1. Secretion of mucus 2. Absorption of the end products 3. Protection against invaders • Submucosa – dense connective tissue containing elastic fibers, blood and lymphatic vessels, lymph nodes, and nerves • Muscularis externa – responsible for segmentation and peristalsis • Serosa – the protective visceral peritoneum Review of Digestive Tract Mucosa - Absorbs food Submucosa - Contains blood vessels and nerves Muscularis -Propels food Serosa - Provides protection Mouth • Oral or buccal cavity: – Is bounded by lips, cheeks, palate, and tongue – Has the oral orifice as its anterior opening – Is continuous with the oropharynx posteriorly • To withstand abrasions: – The mouth is lined with stratified squamous epithelium – The gums, hard palate, and dorsum of the tongue are slightly keratinized Lips and Cheeks • Have a core of skeletal muscles • Labial frenulum – median fold that joins the internal aspect of each lip to the gum • Vestibule – bounded by the lips and cheeks externally, and teeth and gums internally • Oral cavity proper – area that lies within the teeth and gums Lips and Cheeks • Have a core of skeletal muscles • Labial frenulum – median fold that joins the internal aspect of each lip to the gum • Vestibule – bounded by the lips and cheeks externally, and teeth and gums internally • Oral cavity proper – area that lies within the teeth and gums Oral Cavity and Pharynx: Anterior View Palate • There are two palates: – Hard palate – underlain by palatine bones and palatine processes of the maxillae • Assists the tongue in chewing • Slightly corrugated on either side of the raphe (midline ridge) – Soft palate – mobile fold formed mostly of skeletal muscle • Closes off the nasopharynx during swallowing • Uvula projects downward from its free edge and when touched, causes the soft palate to widen. If you forget which is which, use your tongue. Tongue • • Occupies the floor of the mouth and fills the oral cavity when mouth is closed Functions include: 1. Gripping and repositioning food during chewing 2. Mixing food with saliva and forming the bolus 3. Initiation of swallowing, and speech Tongue • Intrinsic muscles change the shape of the tongue • Extrinsic muscles alter the tongue’s position • Lingual frenulum secures the tongue to the floor of the mouth Tongue • Superior surface bears three types of papillae – Filiform – give the tongue roughness and provide friction – Fungiform – scattered widely over the tongue and give it a reddish hue – Circumvallate – V-shaped row in back of tongue • Sulcus terminalis – groove that separates the tongue into two areas: – Anterior 2/3 residing in the oral cavity – Posterior third residing in the oropharynx Tongue Salivary Glands • Produce and secrete saliva that: 1. 2. 3. 4. • • Cleanses the mouth Moistens and dissolves food chemicals Aids in bolus formation Contains enzymes that break down starch Three pairs of extrinsic glands – parotid, submandibular, and sublingual Intrinsic salivary glands (buccal glands) – scattered throughout the oral mucosa Salivary Glands • Parotid – lies anterior to the ear between the masseter muscle and skin – Parotid duct – opens into the vestibule next to the second upper molar • Submandibular – lies along the medial aspect of the mandibular body – Its ducts open at the base of the lingual frenulum • Sublingual – lies anterior to the submandibular gland under the tongue – It opens via 10-12 ducts into the floor of the mouth Pathology: Mumps • A viral disorder infection of the parotid salivary gland. Iowa to launch mass clinics for mumps shots State to target young adults caught up in growing epidemic (4/2006) Control of Salivation • Intrinsic glands keep the mouth moist • Extrinsic salivary glands secrete serous, enzyme-rich saliva in response to: – Ingested food which stimulates chemoreceptors and pressoreceptors – The thought of food • Strong sympathetic stimulation inhibits salivation and results in dry mouth Teeth • Primary – 20 deciduous teeth that erupt between 6 and 24 months • Permanent – enlarge and develop causing the root of deciduous teeth to be resorbed and fall out between the ages of 6 and 12 years – All but the third molars have erupted by the end of adolescence – There are usually 32 permanent Deciduous Teeth Permanent Teeth Classification of Teeth • Teeth are classified according to their shape and function – Incisors – chisel-shaped teeth adapted for cutting or nipping – Canines – conical or fanglike teeth that tear or pierce – Premolars (bicuspids) and molars – have broad crowns with rounded tips and are best suited for grinding or crushing Tooth Structure • Two main regions – crown and the root • Crown – exposed part of the tooth above the gingiva (gum) • Enamel – acellular, brittle material composed of calcium salts and hydroxyapatite crystals is the hardest substance in the body – Encapsules the crown of the tooth • Root – portion of the tooth embedded in the jawbone Tooth Structure • Two main regions – crown and the root (and the intervening neck) • Crown – exposed part of the tooth above the gingiva (gum) • Root – portion of the tooth embedded in the jawbone Tooth Structure • Cementum – calcified connective tissue – Covers the root – Attaches it to the periodontal ligament • Enamel – acellular, brittle material composed of calcium salts and hydroxyapatite crystals is the hardest substance in the body – Encapsules the crown of the tooth Tooth Structure • Dentin – bonelike material deep to the enamel cap that forms the bulk of the tooth • Pulp – connective tissue, blood vessels, and nerves • Root canal – portion of the pulp cavity that extends into the root Tooth Structure Tooth and Gum Disease • Dental caries – gradual demineralization of enamel and dentin by bacterial action 1. Dental plaque, a film of sugar, bacteria, and mouth debris, adheres to teeth 2. Acid produced by the bacteria in the plaque dissolves calcium salts 3. Without these salts, organic matter is digested by proteolytic enzymes 4. Daily flossing and brushing help prevent caries by removing forming plaque Tooth and Gum Disease: Periodontitis • Gingivitis – 1. as plaque accumulates, it calcifies and forms calculus, or tartar 2. Calculus disrupts the seal between the gingivae and the teeth 3. Puts the gums at risk for infection • Periodontitis –Immune system attacks intruders as well as body tissues, carving pockets around the teeth and dissolving bone Normal Pharynx: The Basics – Nasopharynx: just air – Oropharynx: food comes in to epiglottis – Laryngopharynx : epiglottis to the larynx Pathology: Cranial Nerve Lesions • Cranial nerve lesions can lead to paralysis of the tongue(11) or pharynx (10). • Damage to 5, 9 or 10 can lead to difficulty swallowing. Polio, encephalitis, botulism, MD, mysasthenia gravis Esophagus • Muscular tube going from the laryngopharynx to the stomach • Travels through the mediastinum and pierces the diaphragm • Joins the stomach at the cardiac orifice Pathology: Esophageal Cancer • May occlude the esophagus • May impose on the trachea as well. Pathology: GERD (gastroesophageal reflux disorder) Gas is trapped in the fundus of the stomach. – This gas may cause the pyloric valve to become misshapen and open. Either this alone will allow acid access to the sphinchter and esophagus or the escaping gas will carry acid with it. Pathology: Achalasia • The lower esophageal sphincters fails to relax during swallowing. – Minutes to hours and then up until it will hold 1 L Deglutition (Swallowing) • Involves the coordinated activity of the tongue, soft palate, pharynx, esophagus and 22 separate muscle groups • Buccal phase – bolus is forced into the oropharynx • Pharyngeal-esophageal phase – controlled by the medulla and lower pons – All routes except into the digestive tract are sealed off • Peristalsis moves food through the pharynx to the esophagus Pathology: Choking Stomach • Chemical breakdown of proteins begins and food is converted to chyme • Cardiac region – surrounds the cardiac orifice • Fundus – dome-shaped region beneath the diaphragm • Body – midportion of the stomach • Pyloric region – made up of the antrum and canal which terminates at the pylorus • The pylorus is continuous with the duodenum through the pyloric sphincter Stomach Stomach • Greater curvature – entire extent of the convex lateral surface • Lesser curvature – concave medial surface • Lesser omentum – group of ligaments that run from the liver to the lesser curvature • Greater omentum – drapes inferiorly from the greater curvature to the small intestine Omentums Lesser Greater Stomach • Nerve supply – sympathetic and parasympathetic fibers of the autonomic nervous system • Blood supply – celiac trunk, and corresponding veins (part of the hepatic portal system) Stomach Microscopic Anatomy of the Stomach • Muscularis – has an additional oblique layer that: – Allows the stomach to churn, mix, and pummel food physically – Breaks down food into smaller fragments • Epithelial lining is composed of: – Goblet cells that produce a coat of alkaline mucus – Gastric pits contain gastric glands that secrete gastric juice, mucus, and gastrin Microscopic Anatomy of the Stomach Glands of the Stomach Fundus and Body • Gastric glands of the fundus and body have a variety of secretory cells – Mucous neck cells – secrete acid mucus – Parietal cells – secrete HCl and intrinsic factor – Chief cells – produce pepsinogen • Pepsinogen is activated to pepsin by: – HCl in the stomach – Pepsin itself via a positive feedback mechanism – Enteroendocrine cells – secrete gastrin, histamine, endorphins, serotonin, cholecystokinin (CCK), and somatostatin into the lamina propria Stomach Lining • The stomach is exposed to the harshest conditions in the digestive tract • To keep from digesting itself, the stomach has a mucosal barrier with: – A thick coat of bicarbonate-rich mucus on the stomach wall (basic barrier) – Epithelial cells that are joined by tight junctions (no holes for acid to leak through) – Gastric glands that have cells impermeable to HCl (the cells don’t let the acid through) • Also, damaged epithelial cells are quickly replaced Digestion in the Stomach • The stomach: 1. Holds ingested food 2. Degrades this food both physically and chemically 3. Delivers chyme to the small intestine 4. Enzymatically digests proteins with pepsin 5. Secretes intrinsic factor required for absorption of vitamin B12 Release of Gastric Juice Response of the Stomach to Filling • Stomach pressure remains constant until about 1L of food is ingested • Relative unchanging pressure results from reflex-mediated relaxation and plasticity • Reflex-mediated events include: – Receptive relaxation – as food travels in the esophagus, stomach muscles relax – Adaptive relaxation – the stomach dilates in response to gastric filling Gastric Contractile Activity • Peristaltic waves move toward the pylorus at the rate of 3 per minute • This basic electrical rhythm (BER) is initiated by pacemaker cells (cells of Cajal) • Most vigorous peristalsis and mixing occurs near the pylorus • Chyme is either: – Delivered in small amounts to the duodenum or – Forced backward into the stomach for further mixing Gastric Contractile Activity Regulation of Gastric Emptying • Gastric emptying is regulated by: – The neural enterogastric reflex – Hormonal (enterogastrone) mechanisms • These mechanisms inhibit gastric secretion and duodenal filling • Carbohydrate-rich chyme quickly moves through the duodenum • Fat-laden chyme is digested more slowly causing food to remain in the stomach longer (Atkins diet). Regulation of Gastric Emptying Digestive Problems • Ulcers – Peptic ulcer – Helicobactor pylorii infection – Use of certain anti-inflammatory drugs – Disorders that cause excessive acid secretion – Poor mucous production form poor nutrition or circulation. Pathology: Peptic Ulcer • 80% of ulcers are caused by helicobactor pylori. • About 25% of us have H. Pylori in our stomach right now. Gastritis • Inflammation of the stomach. • May be mild to severe. Gastric Atrophy • With prolonged gastritis, it can lead to atrophy. • This can lead to nutritional deficiencies because the stomach makes intrinsic factor, an enzyme necessary to absorbe B12 (and B12 is methionine) Small Intestine: Gross Anatomy • Runs from pyloric sphincter to the ileocecal valve • Has three subdivisions: duodenum, jejunum, and ileum • The bile duct and main pancreatic duct empty into the duodenum. • The jejunum extends from the duodenum to the ileum • The ileum joins the large intestine at the ileocecal valve Small Intestine: Microscopic Anatomy • Structural modifications of the small intestine wall increase surface area – Plicae circulares: deep circular folds of the mucosa and submucosa – Villi – fingerlike extensions of the mucosa – Microvilli – tiny projections of absorptive mucosal cells’ plasma membranes Small Intestine: Microscopic Anatomy Plicae circulares Sprue • Several diseases can caused decreased absorption of the small intestine mucosa. These are termed sprue. – Celiac Disease – Chrohn’s – Ischemic Death of Microvilli • All will cause… – sever nutritional deficiency – Possible osteomalacia – Lack of blood clotting due to loss of Vit. K – Anemia due to lack of Vit. B12 Pathology: Coeliac/Crohn’sDisease Pathology: Coeliac/Crohn’sDisease • Due to a “error in design” the tips of microvilli usually get less oxygen. – The O2 diffuses straight from artery to vein before reaching the tip. • In systemic ischemia, the microvilli can be damaged. Small Intestine: Histology of the Wall • The epithelium of the mucosa is made up of: – Absorptive cells and goblet cells – Enteroendocrine cells – Interspersed T cells called intraepithelial lymphocytes (IELs) Small Intestine: Histology of the Wall • Cells of intestinal crypts secrete intestinal juice • Peyer’s patches are found in the submucosa (lymphatics follicles) • Brunner’s glands in the duodenum secrete alkaline mucus Liver • The largest gland in the body • Superficially has four lobes – right, left, caudate, and quadrate Liver • The falciform ligament: – Separates the right and left lobes anteriorly – Suspends the liver from the diaphragm and anterior abdominal wall Liver: Associated Structures • The lesser omentum anchors the liver to the stomach • The hepatic blood vessels enter the liver at the porta hepatis • The gallbladder rests in a recess on the inferior surface of the right lobe Liver: Associated Structures • Bile leaves the liver via: – Bile ducts, which fuse into the common hepatic duct 1. Liver 2. Common Bile Duct 3. Gall Stones 4. Gall Bladder Jaundice Unconjugated Urobilinogen Blood Conjugated Urobilinogen Jaundice Unconjugated Urobilinogen Blood Conjugated Urobilinogen High Unconjugated Biliruben means… 1. Excess hemolysis • Hemolytic jaundice 2. Liver isn’t converting to conjugated biliruben. • Hepatic Jaundice 3. Blockage of bile duct • Biliary obstruction Liver: Microscopic Anatomy • Hexagonal-shaped liver lobules are the structural and functional units of the liver – Composed of hepatocyte (liver cell) plates radiating outward from a central vein – Portal triads are found at each of the six corners of each liver lobule • Portal triads consist of a bile duct and – Hepatic artery – supplies oxygen-rich blood to the liver – Hepatic portal vein – carries venous blood with nutrients from digestive viscera Microscopic Anatomy of the Liver Liver: Microscopic Anatomy • Hepatocytes’ functions include: 1. 2. 3. 4. Production of bile Processing bloodborne nutrients Storage of fat-soluble vitamins Detoxification Liver: Microscopic Anatomy • Hepatocytes’ functions include: 1. 2. 3. 4. Production of bile Processing bloodborne nutrients Storage of fat-soluble vitamins Detoxification Liver Function Gallbladder and Associated Ducts Pathology: Cirrhosis • Cirrhosis is most commonly caused by alcoholism, hepatitis B and fatty liver disease but has many other possible causes. Hepatitis C is also an important cause. Pathology: Cirrhosis • Cirrhosis is most commonly caused by alcoholism, hepatitis B and fatty liver disease but has many other possible causes. Hepatitis C is also an important cause. Composition of Bile • A yellow-green, alkaline solution containing bile salts, bile pigments, cholesterol, neutral fats, phospholipids, and electrolytes • Bile salts are cholesterol derivatives that: – Emulsify fat – Facilitate fat and cholesterol absorption – Help solubilize cholesterol • The chief bile pigment is bilirubin, a waste product of heme The Gallbladder • Thin-walled, green muscular sac on the ventral surface of the liver • Stores and concentrates bile • Releases bile via the cystic duct, which flows into the bile duct Pathology: Cholecystitis • Inflammation of the gall bladder. • Choleliths (gall stones block the cystic duct. – Leads to inspissation (thickening) of bile, bile stasis, and secondary infection Regulation of Bile Release Pancreas • Location – Lies deep to the greater curvature of the stomach – The head is encircled by the duodenum and the tail abuts the spleen Pancreas • Exocrine function – Secretes pancreatic juice which breaks down all categories of foodstuff – Acini (clusters of secretory cells) contain zymogen granules with digestive enzymes • The pancreas also has an endocrine function – release of insulin and glucagon Acinus of the Pancreas Composition and Function of Pancreatic Juice • Water solution of enzymes and electrolytes (primarily bicarbonate (HCO3–)) – Neutralizes acid chyme – Provides optimal environment for pancreatic enzymes • Enzymes are released in inactive form and activated in the duodenum Composition and Function of Pancreatic Juice • Examples include – Trypsinogen is activated to trypsin – Procarboxypeptidase is activated to carboxypeptidase • Active enzymes secreted – Amylase, lipases, and nucleases – These enzymes require ions or bile for optimal activity Pancreatic Excretions Regulation of Pancreatic Secretion Pancreatitis • Caused by excessive alcohol or gallstones. Digestion in the Small Intestine • As chyme enters the duodenum: – Carbohydrates and proteins are only partially digested – No fat digestion has taken place Digestion in the Small Intestine • Digestion continues in the small intestine 1. Chyme is released slowly into the duodenum 2. Because it is hypertonic and has low pH, mixing is required for proper digestion 3. Required substances needed are supplied by the liver 4. Virtually all nutrient absorption takes place in the small intestine Motility in the Small Intestine • The most common motion of the small intestine is segmentation – It is initiated by intrinsic pacemaker cells (Cajal cells) – Moves contents steadily toward the ileocecal valve • After nutrients have been absorbed: – Peristalsis begins with each wave starting distal to the previous – Meal remnants, bacteria, mucosal cells, and debris are moved into the large intestine Control of Motility • Local enteric neurons of the GI tract coordinate intestinal motility • Cholinergic neurons cause: – Contraction and shortening of the circular muscle layer – Shortening of longitudinal muscle – Distension of the intestine Control of Motility • Other impulses relax the circular muscle • The gastroileal reflex and gastrin: – Relax the ileocecal sphincter – Allow chyme to pass into the large intestine Large Intestine • Has three unique features: – Teniae coli – three bands of longitudinal smooth muscle in its muscularis – Haustra – pocketlike sacs caused by the tone of the teniae coli – Epiploic appendages – fat-filled pouches of visceral peritoneum Large Intestine Large Intestine • Is subdivided into the cecum, appendix, colon, rectum, and anal canal • The saclike cecum: – Lies below the ileocecal valve in the right iliac fossa – Contains a wormlike vermiform appendix Large Intestine Colon • Has distinct regions: ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, and sigmoid colon • The transverse and sigmoid portions are anchored via mesenteries called mesocolons • The sigmoid colon joins the rectum • The anal canal, the last segment of the large intestine, opens to the exterior at the anus Large Intestine Constipation • Slow movement of feces through the large intestine. • Increased time to absorb bicarbonate, which results in alkalosis. • Can lower K+ levels and thus affect heart, neurons, muscles and respiration. • Diarrhea Fast movement of feces through the large intestine. • Electrolytes released to intestine and water follows. • Decreased time to absorb bicarbonate, which results in alkalosis. • Can raise K+ levels and thus affect heart, neurons, muscles and respiration. Hirschsprung’s/Megacolon • http://aliveandwellcoloncare.com/_wsn/pa ge9.html Valves and Sphincters of the Rectum and Anus • The anus has two sphincters: – Internal anal sphincter composed of smooth muscle – External anal sphincter composed of skeletal muscle • These sphincters are closed except during defecation Mesenteries of Digestive Organs Mesenteries of Digestive Organs Mesenteries of Digestive Organs Large Intestine: Microscopic Anatomy • Colon mucosa is simple columnar epithelium except in the anal canal • Has numerous deep crypts lined with goblet cells • Anal canal mucosa is stratified squamous epithelium • Anal sinuses exude mucus and compress feces • Superficial venous plexuses are associated with the anal canal • Inflammation of these veins results in itchy varicosities called hemorrhoids Structure of the Anal Canal Bacterial Flora • The bacterial flora of the large intestine consist of: – Bacteria surviving the small intestine that enter the cecum and – Those entering via the anus • These bacteria: – – – – Colonize the colon Ferment indigestible carbohydrates Release irritating acids and gases (flatus) Synthesize B complex vitamins and vitamin K Functions of the Large Intestine • Other than digestion of enteric bacteria, no further digestion takes place • Vitamins, water, and electrolytes are reclaimed • Its major function is propulsion of fecal material toward the anus • Though essential for comfort, the colon is not essential for life Motility of the Large Intestine • Haustral contractions – Slow segmenting movements that move the contents of the colon – Haustra sequentially contract as they are stimulated by distension • Presence of food in the stomach: – Activates the gastrocolic reflex – Initiates peristalsis that forces contents toward the rectum Defecation • Distension of rectal walls caused by feces: – Stimulates contraction of the rectal walls – Relaxes the internal anal sphincter • Voluntary signals stimulate relaxation of the external anal sphincter and defecation occurs Defecation Digestion Chemical Digestion: Carbohydrates • 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 Chemical Digestion: Proteins • Absorption: similar to carbohydrates • Enzymes used: pepsin in the stomach • Enzymes acting in the small intestine – Pancreatic enzymes – trypsin, chymotrypsin, and carboxypeptidase – Brush border enzymes – aminopeptidases, carboxypeptidases, and dipeptidases Chemical Digestion: Proteins Chemical Digestion: Fats • Absorption: Diffusion into intestinal cells where they: – Combine with proteins and extrude chylomicrons – Enter lacteals and are transported to systemic circulation via lymph • Glycerol and short chain fatty acids are: – Absorbed into the capillary blood in villi – Transported via the hepatic portal vein • Enzymes/chemicals used: bile salts and pancreatic lipase Chemical Digestion: Fats Fatty Acid Absorption • Fatty acids and monoglycerides enter intestinal cells via diffusion • They are combined with proteins within the cells • Resulting chylomicrons are extruded • They enter lacteals and are transported to the circulation via lymph Fatty Acid Absorption Chemical Digestion: Nucleic Acids • Absorption: active transport via membrane carriers • Absorbed in villi and transported to liver via hepatic portal vein • Enzymes used: pancreatic ribonucleases and deoxyribonuclease in the small intestines Electrolyte Absorption • Most ions are actively absorbed along the length of small intestine – Na+ is coupled with absorption of glucose and amino acids – Ionic iron is transported into mucosal cells where it binds to ferritin • Anions passively follow the electrical potential established by Na+ Electrolyte Absorption • K+ diffuses across the intestinal mucosa in response to osmotic gradients • Ca2+ absorption: – Is related to blood levels of ionic calcium – Is regulated by vitamin D and parathyroid hormone (PTH) Water Absorption • 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 • Water uptake is coupled with solute uptake, and as water moves into mucosal cells, substances follow along their concentration gradients Malabsorption of Nutrients • Results from anything that interferes with delivery of bile or pancreatic juice • Factors that damage the intestinal mucosa (e.g., bacterial infection) • Gluten enteropathy (adult celiac disease) – gluten damages the intestinal villi and reduces the length of microvilli – Treated by eliminating gluten from the diet (all grains but rice and corn) Cancer • Stomach and colon cancers rarely have early signs or symptoms • Metastasized colon cancers frequently cause secondary liver cancer • Prevention is by regular dental and medical examinations Cancer • Colon cancer is the 2nd largest cause of cancer deaths in males (lung cancer is 1st) • Forms from benign mucosal tumors called polyps whose formation increases with age • Regular colon examination should be done for all those over 50 Appendicitis •Usually caused by fecal obstruction or anatomical “kinking” of the appendix. •A rupture leads to peritonitis. Diverticulitis •Small herniations of the mucosa in the large intestine. •These areas can become inflamed and possibly rupture. •Prevention is the treatment of choice. A diet high in fiber will help prevent diverticulitis. Diarrhea •Movement of fecal material through the GI Tract too rapidly. •May be caused by microbes, spicy foods, stress, etc. Constipation •Infrequent defecation of fecal material. •Usually caused by a diet low in fiber and water. Buliemia Nervosa •Condition where a patient binges on food and then purges with either laxatives or vomiting. •Considered a psychological disorder where the patient has a fear of gaining weight. •Treated with psychotherapy. Anorexia Nervosa •Psychological disorder where the patient has a false perception of their own weight. •Patient denies their own appetite. •Patients are usually 15 - 20 % below normal body weight. •Extreme cases are lethal. •Closely associated with bulimia nervosa. Flatulence •Excessive intestinal gas resulting from bacteria in the intestines, diet, or swallowing air. Cystic Fibrosis •Genetic disorder where excess mucous is produced. •Causes a blocking of the pancreatic duct, therefore enzymes cannot enter the duodenum from the pancreas. •Treated by giving digestive enzymes orally. Nutrition, Metabolism, and Body Temperature Regulation Nutrition • Nutrient – a substance that promotes normal growth, maintenance, and repair • Major nutrients – carbohydrates, lipids, and proteins • Other nutrients – vitamins and minerals (and technically speaking, water) Carbohydrates • Complex carbohydrates (starches) are found in bread, cereal, flour, pasta, nuts, and potatoes • Simple carbohydrates (sugars) are found in soft drinks, candy, fruit, and ice cream • Glucose is the molecule ultimately used by body cells to make ATP • Neurons and RBCs rely almost entirely upon glucose to supply their energy needs • Excess glucose is converted to glycogen or fat and stored Lipids • The most abundant dietary lipids, triglycerides, are found in both animal and plant foods • Essential fatty acids – linoleic and linolenic acid, found in most vegetables, must be ingested • Dietary fats: – Help the body to absorb vitamins – Are a major energy fuel of hepatocytes and skeletal muscle – Are a component of myelin sheaths and all cell membranes Proteins • Proteins supply: – Essential amino acids, the building blocks for nonessential amino acids – Nitrogen for nonprotein nitrogen-containing substances • Daily intake should be approximately 0.8g/kg of body weight Vitamins • Organic (carbon) compounds needed for growth and good health • They are crucial in helping the body use nutrients and often function as coenzymes • Only vitamins D, K, and B are synthesized in the body; all others must be ingested • Water-soluble vitamins (B-complex and C) are absorbed in the gastrointestinal tract – B12 additionally requires gastric intrinsic factor to be absorbed Minerals • Seven minerals are required in moderate amounts – Calcium, phosphorus, potassium, sulfur, sodium, chloride, and magnesium • Dozens are required in trace amounts • Minerals work with nutrients to ensure proper body functioning • Calcium, phosphorus, and magnesium salts harden bone Minerals • Sodium and chloride help maintain normal osmolarity, water balance, and are essential in nerve and muscle function • Uptake and excretion must be balanced to prevent toxic overload Metabolism • Metabolism – all chemical reactions necessary to maintain life • Cellular respiration – food fuels are broken down within cells and some of the energy is captured to produce ATP – Anabolic reactions – synthesis of larger molecules from smaller ones – Catabolic reactions – hydrolysis of complex structures into simpler ones Metabolism • Enzymes shift the high-energy phosphate groups of ATP to other molecules • These phosphorylated molecules are activated to perform cellular functions Stages of Metabolism • Energy-containing nutrients are processed in three major stages 1. Digestion – breakdown of food; nutrients are transported to tissues 2. Anabolism and formation of catabolic intermediates where nutrients are: 1. Built into lipids, proteins, and glycogen 2. Broken down by catabolic pathways to pyruvic acid and acetyl CoA 3. Oxidative breakdown – nutrients are catabolized to carbon dioxide, water, and ATP Stages of Metabolism Carbohydrate Metabolism • Since all carbohydrates are transformed into glucose, it is essentially glucose metabolism • Oxidation of glucose is shown by the overall reaction: C6H12O6 + 6O2 6H2O + 6CO2 + 36 ATP + heat • Glucose is catabolized in three pathways 1. Glycolysis 2. Krebs cycle 3. The electron transport chain and oxidative phosphorylation Carbohydrate Catabolism Glycolysis • A three-phase pathway in which: 1. Glucose is oxidized into pyruvic acid 2. NAD+ is reduced to NADH + H+ 3. ATP is synthesized by substrate-level phosphorylation • Pyruvic acid: – Moves on to the Krebs cycle in an aerobic pathway (with O2) – Is reduced to lactic acid in an anaerobic environment (if no O2) 3 Outcomes of Glycolysis 3. ATP is synthesized by substrate-level phosphorylation 2. NAD+ is reduced to NADH + H+ 1. Glucose is oxidized into pyruvic acid Glycolysis: Phase 1 and 2 • Phase 1: Sugar activation – Two ATP molecules activate glucose into fructose-1,6-diphosphate • Phase 2: Sugar cleavage – Fructose-1,6-bisphosphate is cleaved into two 3-carbon isomers • Bishydroxyacetone phosphate • Glyceraldehyde 3-phosphate Glycolysis: Phase 3 • Phase 3: Oxidation and ATP formation – The 3-carbon sugars are oxidized (reducing NAD+) – Inorganic phosphate groups (Pi) are attached to each oxidized fragment – The terminal phosphates are cleaved and captured by ADP to form four ATP molecules Glycolysis: Phase 3 • The final products are: 1. Two pyruvic acid molecules 2. Two NADH + H+ molecules (reduced NAD+) 3. A net gain of two ATP molecules Krebs Cycle: Preparatory Step • Occurs in the mitochondrial matrix and is fueled by pyruvic acid and fatty acids Krebs Cycle: Preparatory Step • Pyruvic acid is converted to acetyl CoA in three main steps: 1. Decarboxylation • • Carbon is removed Carbon dioxide is released 2. Oxidation • • Hydrogen atoms are removed from pyruvic acid NAD+ is reduced to NADH + H+ 3. Formation of acetyl CoA – the resulting acetic acid is combined with coenzyme A, a sulfur-containing coenzyme, to form acetyl CoA Krebs Cycle • An eight-step cycle in which each acetic acid is decarboxylated and oxidized, generating: 1. 2. 3. 4. • Three molecules of NADH + H+ One molecule of FADH2 Two molecules of CO2 One molecule of ATP For each molecule of glucose entering glycolysis, two molecules of acetyl CoA enter the Krebs cycle Krebs Cycle Electron Transport Chain • Food (glucose) is oxidized and the released hydrogens: 1. Are transported by coenzymes NADH and FADH2 2. Enter a chain of proteins bound to metal atoms (cofactors) 3. Combine with molecular oxygen to form water 4. Release energy • The energy released is harnessed to attach inorganic phosphate groups (Pi) to ADP, making ATP by oxidative phosphorylation Mechanism of Oxidative Phosphorylation • The hydrogens delivered to the chain are split into protons (H+) and electrons – The protons are pumped across the inner mitochondrial membrane by: • NADH dehydrogenase (FMN, Fe-S) • Cytochrome b-c1 • Cytochrome oxidase (a-a3) – The electrons are shuttled from one acceptor to the next Mechanism of Oxidative Phosphorylation 1. Electrons are delivered to oxygen, forming oxygen ions 2. Oxygen ions attract H+ to form water 3. H+ pumped to the intermembrane space: – Diffuses back to the matrix via ATP synthase – Releases energy to make ATP Mechanism of Oxidative Phosphorylation 1. Hydrogens are split into protons and electrons Mechanism of Oxidative Phosphorylation 2. Protons are shuttled across membrane Mechanism of Oxidative Phosphorylation 3. Electrons cross membrane as well but fall back sooner Mechanism of Oxidative Phosphorylation 4. When electrons fall back, you have 2 gradients, a pH gradient and a strong charge gradient Mechanism of Oxidative Phosphorylation 5. When H comes back, it can give off energy that is used to make ATP Summary of ATP Production Lipid Metabolism • Most products of fat metabolism are transported in lymph as chylomicrons • Lipids in chylomicrons are hydrolyzed by plasma enzymes and absorbed by cells • Catabolism of fats involves two separate pathways Glycerol Fatty Acids – Glycerol pathway – Fatty acids pathway Lipid Metabolism Lipogenesis and Lipolysis • Excess dietary glycerol and fatty acids undergo lipogenesis to form triglycerides • Glucose is easily converted into fat since acetyl CoA is: – An intermediate in glucose catabolism – The starting molecule for the synthesis of fatty acids Lipogenesis and Lipolysis • Lipolysis, the breakdown of stored fat, is essentially lipogenesis in reverse • Oxaloacetic acid is necessary for the complete oxidation of fat – Without it, acetyl CoA is converted into ketones (ketogenesis) Lipogenesis and Lipolysis The main point here is that lipids and sugars are interconvertible Protein Metabolism • Excess dietary protein results in amino acids being: – Oxidized for energy – Converted into fat for storage • Amino acids must be deaminated prior to oxidation for energy Protein Metabolism Synthesis of Proteins • Amino acids are the most important anabolic nutrients, and they form: – All protein structures – The bulk of the body’s functional molecules State of the Body • The body exists in a dynamic catabolicanabolic state • Organic molecules (except DNA) are continuously broken down and rebuilt • The body’s total supply of nutrients constitutes its nutrient pool Absoprtive and Postabsorptive States • Metabolic controls equalize blood concentrations of nutrients between two states • Absorptive – The time during and shortly after nutrient intake • Postabsorptive – The time when the GI tract is empty – Energy sources are supplied by the breakdown of body reserves Absorptive State (Full Stomach) • The major metabolic thrust is anabolism and energy storage – Amino acids become proteins – Glycerol and fatty acids are converted to triglycerides – Glucose is stored as glycogen • Dietary glucose is the major energy fuel • Excess amino acids are deaminated and used for energy or stored as fat in the liver Absorptive State Principal Pathways of the Absorptive State • In muscle: – Amino acids become protein – Glucose is converted to glycogen • In the liver: – Amino acids become protein or are deaminated to keto acids – Glucose is stored as glycogen or converted to fat Principal Pathways of the Absorptive State • In adipose tissue: – Glucose and fats are converted and stored as fat • All tissues use glucose to synthesize ATP Principal Pathways of the Absorptive State Insulin Effects on Metabolism • Insulin controls the absorptive state and its secretion is stimulated by: – Increased blood glucose – Elevated amino acid levels in the blood – Gastrin, CCK, and secretin • Insulin enhances: – Active transport of amino acids into tissue cells – Facilitated diffusion of glucose into tissue Insulin Effects on Metabolism Diabetes Mellitus • A consequence of inadequate insulin production (Type I) or abnormal insulin receptors (Type II) • Glucose becomes unavailable to most body cells • Metabolic acidosis, protein wasting, and weight loss result as fats and tissue proteins are used for energy Postabsorptive State • The major metabolic thrust is catabolism and replacement of fuels in the blood – Proteins are broken down to amino acids – Triglycerides are turned into glycerol and fatty acids – Glycogen becomes glucose • Glucose is provided by glycogenolysis and gluconeogenesis • Fatty acids and ketones are the major energy fuels • Amino acids are converted to glucose in the liver Postabsorptive State Principle Pathways in the Postabsorptive State • In muscle: – Protein is broken down to amino acids – Glycogen is converted to ATP and pyruvic acid (lactic acid in anaerobic states) Principle Pathways in the Postabsorptive State • In the liver: – Amino acids, pyruvic acid, stored glycogen, and fat are converted into glucose – Fat is converted into keto acids that are used to make ATP • Fatty acids (from adipose tissue) and ketone bodies (from the liver) are used in most tissue to make ATP • Glucose from the liver is used by the nervous system to generate ATP Principle Pathways in the Postabsorptive State Hormonal and Neural Controls of the Postabsorptive State • Decreased plasma glucose concentration and rising amino acid levels stimulate alpha cells of the pancreas to secrete glucagon (the antagonist of insulin) • Glucagon stimulates: – Glycogenolysis and gluconeogenesis – Fat breakdown in adipose tissue – Glucose sparing Hormonal and Neural Controls of the Postabsorptive State • In response to low plasma glucose, the sympathetic nervous system releases epinephrine, which acts on the liver, skeletal muscle, and adipose tissue to mobilize fat and promote glycogenolysis Cholesterol • Is the structural basis of bile salts, steroid hormones, and vitamin D • Makes up part of the hedgehog molecule that directs embryonic development • Is transported to and from tissues via lipoproteins Cholesterol • Lipoproteins are classified as: – HDLs – high-density lipoproteins have more protein content – LDLs – low-density lipoproteins have a considerable cholesterol component – VLDLs – very low density lipoproteins are mostly triglycerides Lipoproteins • High levels of HDL are thought to protect against heart attack • High levels of LDL, especially lipoprotein (a), increase the risk of heart attack Metabolic Rate • Rate of energy output (expressed per hour) equal to the total heat produced by: – All the chemical reactions in the body – The mechanical work of the body • Measured directly with a calorimeter or indirectly with a respirometer Metabolic Rate • Basal metabolic rate (BMR) – Reflects the energy the body needs to perform its most essential activities • Total metabolic rate (TMR) – Total rate of kilocalorie consumption to fuel all ongoing activities Factors that Influence BMR • Surface area, age, gender, stress, and hormones • As the ratio of surface area to volume increases, BMR increases • Males have a disproportionately high BMR • Stress increases BMR • Thyroxine increases oxygen consumption, cellular respiration, and BMR