Lecture 12: Digestive Physiology BIO108 PDF

Lecture 12: Digestive Physiology BIO108 - General Physiology Thucydides L. Salunga, Ph.D. © 2015 Pearson Education Ltd Digestive System Interactions © 2015 Pearson Education Ltd  Digestion and Nutrition Nutrition – includes all of those processes by...

Lecture 12: Digestive Physiology BIO108 - General Physiology Thucydides L. Salunga, Ph.D. © 2015 Pearson Education Ltd Digestive System Interactions © 2015 Pearson Education Ltd  Digestion and Nutrition Nutrition – includes all of those processes by which an animal takes in, digests, absorbs, stores and uses food (nutrients) to meet its metabolic needs Digestion – chemical and/or mechanical breakdown of food into particles that the individual cells of an animal can absorb. An animal’s diet must provide Chemical energy for cellular processes Organic building blocks for macromolecules Essential nutrients © 2015 Pearson Education Ltd  Ingestion is the act of eating or feeding Digestion is the process of breaking food down into molecules small enough to absorb Absorption is uptake of nutrients by body cells Elimination is the passage of undigested material out of the digestive system Mechanical digestion 1 INGESTION Chemical digestion 2 DIGESTION (enzymatic hydrolysis) Nutrient 3 ABSORPTION molecules enter body cells 4 ELIMINATION Undigested material © 2015 Pearson Education Ltd  Dietary categories 1. Herbivores - plant life © 2015 Pearson Education Ltd  Dietary categories 2. Carnivores - herbivores and other carnivores © 2015 Pearson Education Ltd  Dietary categories 3. Omnivores - plants and animals © 2015 Pearson Education Ltd  Dietary categories 4. Saprophagous - decaying organic matter Woodlice (Trachelipus deer fly (Chrysops callidus) ratzeburgii) hermit beetle (Osmoderma eremita) © 2015 Pearson Education Ltd red ant (Formica pallidefulva )  Dietary categories Insectivores/Insectivorous – animals that feed primarily on arthropods Photo: CSIRO © 2015 Pearson Education Ltd  Feeding Adaptations 1. Suspension Feeders Many aquatic animals are suspension feeders, which sift small food particles from the water Filter feeding Baleen © 2015 Pearson Education Ltd  Feeding Adaptations 2. Substrate feeders are animals that live in or on their food source Substrate feeding Caterpillar © 2015 Pearson Education Ltd Feces  Feeding Adaptations 3. Fluid feeders suck nutrient-rich fluid from a living host Fluid feeding © 2015 Pearson Education Ltd  Feeding Adaptations 4. Bulk feeders eat relatively large pieces of food Bulk feeding © 2015 Pearson Education Ltd  Feeding Adaptations 5. Deposit feeder – eats its way through dirt or sediments and extract partially decayed organic material (detritus) consumed along with the soil or sediments © 2015 Copyright © 2002 Pearson Education Ltd Pearson Education, Inc., publishing as Benjamin Cummings Earthworm  Intracellular Digestion protists and sponges - cells take in food and break it down via enzymes within the cell. food particles are engulfed by phagocytosis food vacuoles, containing food, fuse with lysosomes containing hydrolytic enzymes © 2015 Pearson Education Ltd  Extracellular Digestion breakdown of food via enzymes usually occurs within a special organ or cavity. occurs in compartments that are continuous with the outside of the animal’s body large animals have special organs for digestion. © 2015 Pearson Education Ltd  Mouth Tentacles Food 1 Digestive enzymes are released from a gland cell. 2 Enzymes break food down into small particles. 3 Food particles are engulfed and digested in food vacuoles. Epidermis Gastrodermis © 2015 Pearson Education Ltd  Digestive Systems Incomplete digestive system – A saclike gut with one opening in the body surface for food to enter and waste to leave Complete digestive system – A tubular gut with an opening at both ends – Includes mouth, pharynx, esophagus, stomach, small and large intestines, and anus © 2015 Pearson Education Ltd  Digestive Digestive Structures: Systems Vertebrates ▪ a one-way system leading from the mouth, pharynx, esophagus, stomach, small intestine, large intestine, rectum and anus. ▪accessory glands of the mammalian digestive system are three pairs of salivary glands, the liver, and the gallbladder © 2015 Pearson Education Ltd  Diversity in Digestive Structures The evolution and structure of the digestive system in various animals reflect their: – Eating habits – Their rate of metabolism – Their body size © 2015 Pearson Education Ltd  Dietary Adaptations ▪A tongue or tongue-like structure evolved in the floor cavity of many vertebrates. Figure 27.6b Fish Tongue. © 2015 Pearson Education Ltd  Diversity in Digestive Structures: Vertebrates Frogs, salamanders, and some lizards can rapidly project part of the tongue from the mouth to capture an insect. http://www.nature.com/nature/journal/v389/n6646/fig_t ab/389027b0_F1.html © 2015 Pearson Education Ltd  Dietary Adaptations Figure 27.6c A Chameleon Catching an Insect. © 2015 Pearson Education Ltd  Dietary Adaptations www.nebraskabirds.org Figure 27.6d The Tongue of a Woodpecker. © 2015 Pearson Education Ltd  Dietary Adaptations ▪ Bird adaptations Size and shape of bills adapted to different diets © 2015 Pearson Education Ltd  Dietary Adaptations rhamphotheca.tumblr.com www.reddit.com © 2015 Pearson Education Ltd  Dietary Adaptations Mammal adaptations – Teeth adapted to different diets © 2015 Pearson Education Ltd  Dietary Adaptations employ toxins that paralyze Figure 27.6a or kill prey at time of capture Rasping Tongue of a Lamprey. © 2015 Pearson Education Ltd  Dietary Adaptations ▪distensible jaw in fishes © 2015 Pearson Education Ltd  Dietary Adaptations distensible jaw in snakes © 2015 Pearson Education Ltd  Dietary Adaptations © 2015 Pearson Education Ltd  Dietary Adaptations Bird adaptations – Crops and gizzards © 2015 Pearson Education Ltd  Mammalian Digestive Systems Multiple stomach chambers in ruminants Figure 27.9 Ruminant Mammal. © 2015 Pearson Education Ltd  Some Adaptations of Mammalian Digestive Systems © 2015 Pearson Education Ltd  Chambers of the Stomach Rumen © 2015 Pearson Education Ltd  Chambers of the Stomach Reticulum © 2015 Pearson Education Ltd  Chambers of the Stomach Omasum © 2015 Pearson Education Ltd  Chambers of the Stomach Abomasum © 2015 Pearson Education Ltd  The Human Digestive System © 2015 Pearson Education Ltd  Three Categories 1. Batch reactors blind tubes or cavities that receive food and eliminate wastes in a pulsed fashion one batch is processed and eliminated before the next one is brought in E.g. Coelenterates © 2015 Pearson Education Ltd  2. Continuous-flow stirred tank reactor GI tract extending through the organism and open at both ends Processing goes on continuously with new food ingested while older food is still being processed E.g. forestomach of ruminants © 2015 Pearson Education Ltd  3. Plug-flow reactor bolus of food is progressively digested as it winds its way through a long, tube like digestive reactor Composition of food varies according to its position along the reactor tube E.g. vertebrate midgut © 2015 Pearson Education Ltd  High quality food - maximum energy is extracted with minimal time spent if the reactor Low quality food – requires a longer periods spent in the reactor and longer transit times trough the GI tract © 2015 Pearson Education Ltd  Transit time through the GI tract – mean retention time o varies with anatomic design, body mass and body temperature © 2015 Pearson Education Ltd  Digestive System of Invertebrates Variation is observed Simple to highly complex Headgut, midgut and hindgut © 2015 Pearson Education Ltd  Digestive System of Vertebrates Parts: Headgut – receives ingested material Midgut – digests and absorbs nutrients Hindgut – absorbs water before digetsive materials are espelled during defecation © 2015 Pearson Education Ltd  the length of the vertebrate digestive system is also correlated with diet Small intestine Small intestine Stomach Cecum Colon (large Carnivore intestine) Herbivore © 2015 Pearson Education Ltd  1. Food is partially digested in the mouth and forced into the pharynx by swallowing 2. Food is moved through the esophagus by peristalsis through a sphincter to the stomach, which adds acids and enzymes to food and mixes them together to form chyme 3. In the small intestine, carbohydrates, lipids and proteins are digested by secretions from liver and pancreas; nutrients and water are absorbed 4. The large intestine absorbs water and ions, and compacts wastes, which collect in the rectum, and are expelled from the anus © 2015 Pearson Education Ltd  The Human Digestive System © 2015 Pearson Education Ltd  1. Food is partially digested in the mouth and forced into the pharynx by swallowing 2. Food is moved through the esophagus by peristalsis through a sphincter to the stomach, which adds acids and enzymes to food and mixes them together to form chyme 3. 3. In the small intestine, carbohydrates, lipids and proteins are digested by secretions from liver and pancreas; nutrients and water are absorbed 4. 4. The large intestine absorbs water and ions, and compacts wastes, which collect in the rectum, and are expelled from the anus © 2015 Pearson Education Ltd Histological layers of the alimentary canal Histolo © 2015 Pearson Education Ltd  waves of contraction of circular muscle behind the gut and relaxation in front of bolus sweeps food down the gut alternate constriction of rings of smooth muscle of the intestine constantly divide and squeeze contents back and forth for mixing of food Segmentation of the intestine © 2015 Pearson Education Ltd  Tongue Oral cavity Salivary Mouth glands Pharynx Salivary glands Esophagus Esophagus Gall- Stomach Liver bladder Sphincter Small Gall- Liver intestine bladder Sphincter Pancreas Stomach Pancreas Large Small intestine intestine Anus Rectum Large intestine Duodenum of Rectum small intestine Anus © 2015 Pearson Education Ltd  Process of Deglutition © 2015 Pearson Education Ltd  1.Digestion begins when teeth mechanically break down food into smaller bits making the food easier to swallow and increasing its surface area. 2. Presence of food stimulates the salivary glands to deliver saliva through ducts to the oral cavity. 3.Saliva initiates chemical digestion while also protecting the oral cavity. 4.Amylase (enzyme in the saliva) hydrolyses starch and glycogen into smaller polysaccharides and the disaccharide maltose. 5.Musin, a sliperry glycoprotein in saliva, protects the lining of the mouth from abrasion. it also lubricates food for easier swallowing. 6.Saliva also contains buffers which neutralizes acid thus preventing tooth decay. 7.Tongue – helps distinguish which food (taste buds) should be processed further. 8.Tongue movement manipulate the food, helping shape it into a ball called bolus. 9.During swallowing tongue helps by pushing the bolus to the back of the oral cavity and into the pharynx. © 2015 Pearson Education Ltd  The sphincters of the food tube © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd  Stomach Structure Stores food and controls the rate of passage to the small intestine Mechanically mixes and breaks down food Secretes substances used in chemical digestion © 2015 Pearson Education Ltd  1. Structure of the stomach wall. The outermost layer, the serosa, is connective tissue covered by epithelium. Beneath the serosa, three layers of smooth muscle differ in their orientation and direction 2. The stomach has three digestive functions Stores food and controls the rate of passage to the small intestine Mechanically mixes and breaks down food Secretes substances used in chemical digestion Cardiac end and pyloric end 3. Stomach mucosa secretes gastric fluid containing hydrochloric acid and enzymes that begin protein digestion Gastrin signals secretion of acid and pepsinogens Acid unfolds proteins Pepsin breaks proteins into peptides Chyme passes into the small intestine © 2015 Pearson Education Ltd  Three major glandular regions of the stomach cardiac glandular mucosa - with mucus secreting cells (mucus neck cells) oxyntic glandular mucosa - with parietal cells pyloric glandular mucosa - with chief cells © 2015 Pearson Education Ltd  Chemical Digestion in the Stomach Gastric juice has a low pH of about 2, which kills bacteria and denatures proteins Gastric juice is made up of hydrochloric acid (HCl) and pepsin Pepsin is a protease, or protein-digesting enzyme, that cleaves proteins into smaller peptides © 2015 Pearson Education Ltd  Parietal cells secrete hydrogen and chloride ions separately into the lumen (cavity) of the stomach Stomach Gastric pit on the interior Epithelium 3 surface of stomach Pepsinogen Pepsin 2 HCl (active Gastric gland Chief enzyme) 1 cell H+ Cl− Mucous cell Parietal Chief cell cell Parietal cell © 2015 Pearson Education Ltd  Chief cells secrete inactive pepsinogen, which is activated to pepsin when mixed with hydrochloric acid in the stomach Mucus protects the stomach lining from gastric juice Stomach Gastric pit on the interior Epithelium 3 surface of stomach Pepsinogen Pepsin 2 HCl (active Gastric gland Chief enzyme) 1 cell −H+ Cl Mucous cell Parietal Chief cell cell Parietal cell © 2015 Pearson Education Ltd  3 Production of gastric juice Pepsinogen Pepsin 1 Pepsinogen and 2 (active HCl secreted into HCl enzyme) lumen Chief 1 cell 2 HCl converts pepsinogen to pepsin. H+ Cl− 3 Pepsin activates more pepsinogen, starting a chain Parietal reaction. cell © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd  Gastric ulcers, lesions in the lining, are caused mainly by the bacterium Helicobacter pylori © 2015 Pearson Education Ltd  Midgut Major site for chemical digestion of proteins, fats, and CHO Digested materials are absorbed in the midgut and transported away from GI tract to the blood © 2015 Pearson Education Ltd  Small Intestine Duodenum – lining secretes mucus and fluid; receives secretion from pancreas and liver Jejunum – secretes fluid, digestion and absorpion Ileum – absorption © 2015 Pearson Education Ltd  Intestinal Epithelium amplify the surface area available for absorption of nutrients. Rate of absorption - proportional to the area of the apical surface membrane of the cells lining the epithelium. Circular folds - slow the progress of food through the intestine, allowing more time for digestion © 2015 Pearson Education Ltd  Intestinal Epithelium © 2015 Pearson Education Ltd  1. A villus covered with the mucosal epithelium, which consists primarily of absorptive cells and occasional goblet cells. 2. Within each villus is a network of blood vessels formed by arterioles, capillaries and venules. A network of lymph vessels, the largest of which is the central lacteal. 3. Nutrients taken up from the intestine are transferred into the blood and lymph vessels for transport to other tissues; the central lacteal can take up large particles. 4. The membrane of microvillus is continuous with the plasma membrane of the epithelium and surrounds with the plasma membrane of the epithelium and surrounds the actin filaments that form cross-bridge links with myosin filaments present in the base of each microvillus. 5. Intermittent actin-myosin interaction produces rhythmic motions of the microvilli which are thought to help mix and exchange the intestinal chyme near the absorptive area. © 2015 Pearson Education Ltd  6. Adjacent absorptive area are held together by desmosomes. 7. Near the apex, the tight junctions with neighboring cells from the zonula occludens that encircle each cells. 8. The tight junctions are especially tight in the interstitial epithelium, so that the apical membranes of the absorptive cells effectively form a continuous sheet of membrane without breaks between cells. 9. Because of the virtual impermeability of the tight junctions, all nutrients must pass across the apical membrane and through the absorptive cell cytoplasm to get from the lumen to the blood and lymph vessels within the villi. 10. Little paracellular passage occurs. © 2015 Pearson Education Ltd  This figure shows the enormous amplifying effect that the microstructure of the mammalian intestine has on its surface area and thus on its absorptive properties © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd  Hindgut Consolidates undigested material and bacteria growing into the hindgut into feces Feces pass into the cloaca/rectum and then expelled through anus (defecation) Absorption of inorganic ions and excess water © 2015 Pearson Education Ltd  Major site for bacterial digestion of intestinal contents in some herbivores Large animals – hindgut fermenters – colon as a modified plug-flow reactor Smaller hindgut fermenters - reactor cecum acts as a continuous-flow, stirred-tank © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd  Accessory Organs Accessory organs along the length of the gut secrete enzymes and other substances that break down food into its component molecules – Salivary glands – Pancreas – Liver – Gallbladder © 2015 Pearson Education Ltd  Liver and Pancreas 1.Digestion of fats and other lipids begins in the small intestine and relies on the production of bile (mixture of substances that is made by the liver). 2.Bile – contains bile salt, which act as detergents/emulsifiers that aid in digestion and absorption of lipids. 3.Bile is stored and concentrated in the gallbladder. © 2015 Pearson Education Ltd  Liver Function The liver detoxifies dangerous substances (alcohol, NH3), and stores fat-soluble vitamins (A, D) and glucose (as glycogen) Between meals, the liver provides the brain with glucose by breaking down stored glycogen © 2015 Pearson Education Ltd  Lipid (fat) digestion in the small intestine requires enzymes and bile, which is produced by the liver and stored in the gallbladder Bile – A mixture of salts, pigments, cholesterol and lipids that emulsifies fats into small drops that enzymes can break down into fatty acids and monoglycerides © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd  Liver and Gallbladder The liver detoxifies dangerous substances (alcohol, NH3), and stores fat-soluble vitamins (A, D) and glucose (as glycogen) Between meals, the liver provides the brain with glucose by breaking down stored glycogen © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd  Liver and Gallbladder Gallbladder – small green sac embedded in the inferior surface of the liver - stores bile secreted by the liver © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd  Pancreas: Two components 1. exocrine portion – produces digestive enzymes in the alveoli (acini) which is transported via pancreatic ducts to the duodenum 2. endocrine portion – bears pancreatic islets (islands of Langerhans), lacks ducts; secretes its hormonal products, insulin and glucagon, into the bloodstream © 2015 Pearson Education Ltd  BORBORYGMI rumbling sounds are normal part of digestion. generated from muscular activity in the stomach and small intestine as food, gas, and fluids are mixed together and pushed through the intestine © 2015 Pearson Education Ltd  Control of Motility Intrinsic control oMyogenic - muscles are capable of producing an intrinsic cycle of electrical activity that leads to muscle contraction without external neuronal stimulation. oBER – basic electric rhythm – rhythmic depolarization and repolarization generated by pacemaker cells of the alimentary canal in mammals © 2015 Pearson Education Ltd  Extrinsic control Control of Motility oGastrointestinal peptide hormones oAutonomic nervous system ▪Parasympathetic (cholinergic neurons) – myenteric & submucosal plexi; excitatory ▪Sympathetic – inhibitory; postganglionic neurons; norepinephrine © 2015 Pearson Education Ltd  Extrinsic Control © 2015 Pearson Education Ltd  Digestive Secretions © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd  Pepsin 1.The powerful proteolytic enzyme pepsin is secreted in an inactive form (pepsinogen), which is then activated by HCl. 2.The chief cells in the gastric glands secrete pepsinogen, while the parietal © 2015 Pearson cells secrete HCl as well as intrinsic factor Education Ltd  Regulation of Digestion © 2015 Pearson Education Ltd  1. CCK – cholecystokinin – amino acids and fatty acids trigger its release; stimulates release of enzymes from the pancreas and of bile from the gallbladder. 2. Secretin – stimulates the pancreas to release sodium bicarbonate, which neutralizes chyme 3. Gastrin – circulates via the bloodstrema back to the stomach, where it stimulates production of gastric juices 4. When chyme rich fats enters the duodenum, secretin and CCK inhibits peristalsis and acid secretion by the stomach, thereby slowing digestion. © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd  CARBOHYDRATE DIGESTION ORAL Polysaccharides Disaccharides CAVITY, (starch, glycogen) (sucrose, lactose) PHARYNX, ESOPHAGUS Salivary amylase Smaller Maltose polysaccharides PROTEIN DIGESTION STOMACH Proteins Pepsin Small polypeptides NUCLEIC ACID DIGESTION FAT DIGESTION SMALL DNA, RNA Fat (triglycerides) INTESTINE (enzymes Pancreatic amylases from Pancreatic trypsin and Pancreatic pancreas) chymotrypsin nucleases Disaccharides Nucleotides Pancreatic lipase Smaller polypeptides Pancreatic carboxypeptidase Glycerol, fatty acids, Small peptides monoglycerides SMALL Nucleotidases INTESTINE (enzymes Dipeptidases, carboxy- Nucleosides from Disaccharidases peptidase, and intestinal aminopeptidase Nucleosidases epithelium) and phosphatases Nitrogenous bases, Monosaccharides Amino acids sugars, phosphates © 2015 Pearson Education Ltd  Nutrient Uptake in the Intestine © 2015 Pearson Education Ltd  Transport of Nutrients in the blood Products of TGC digestion Form micelles w/ bile salts Micelles transport products to the brush border Products enter absorptive cells w/in cells resynthesized into TGC in the ER TGC + phospholipids& cholesterol = chylomicrons stored in Golgi complex Chylomicrons enter central lacteal Circulating blood © 2015 Pearson Education Ltd  Lipid digestion and absorption © 2015 Pearson Education Ltd  Water and Electrolyte Balance in the Gut Ion re-absorption in the lower part of SI Most water & electrolyte absorption occurs at or near the tips of the villi Fluid fluxes occur all along the length of the GI tract Excessive uptake of water – constipation and prevented by gastrin, CCK, cholic acid and fatty acids © 2015 Pearson Education Ltd  Regulation of Digestion Each step in the digestive system is activated as needed The enteric division of the nervous system helps to regulate the digestive process The endocrine system also regulates digestion through the release and transport of hormones © 2015 Pearson Education Ltd  1 2 Liver Food Gallbladder Bile Stomach Chyme Gastric Gastrin juices CCK Pancreas HCO3−, enzymes Duodenum of small intestine Secretin CCK 3 Secretin and CCK Gastric juices Stimulation Inhibition © 2015 Pearson Education Ltd  Regulation of Energy Storage The body stores energy-rich molecules that are not needed right away for metabolism In humans, energy is stored first in the liver and muscle cells in the polymer glycogen Excess energy is stored in fat in adipose cells When fewer calories are taken in than expended, the human body expends liver glycogen first, then muscle glycogen and fat © 2015 Pearson Education Ltd  Glucose Homeostasis Glucose is a major fuel for cellular respiration and a key source of carbon skeletons for biosynthesis The hormones insulin and glucagon regulate the breakdown of glycogen into glucose The liver is the site for glucose homeostasis A carbohydrate-rich meal raises insulin levels, which triggers the synthesis of glycogen Low blood sugar causes glucagon to stimulate the breakdown of glycogen and release glucose © 2015 Pearson Education Ltd  Insulin Transport of Secretion glucose into of insulin body cells by beta and storage cells of the of glucose pancreas as glycogen Blood glucose Blood glucose level rises level falls. (such as after eating). NORMAL BLOOD GLUCOSE (70–110 mg glucose/ 100 mL) Blood glucose Blood glucose level rises. level falls (such as after fasting). Secretion of Breakdown of glucagon by glycogen and alpha cells release of of the glucose into blood Glucagon pancreas © 2015 Pearson Education Ltd  Insulin acts on nearly all body cells to stimulate glucose uptake from blood Brain cells are an exception; they can take up glucose whether or not insulin is present Glucagon and insulin are both produced in the islets of the pancreas Alpha cells make glucagon and beta cells make insulin © 2015 Pearson Education Ltd Regulation of Appetite and Consumption a) Overnourishment causes obesity, which results from excessive intake of food energy with the excess stored as fat b) Obesity contributes to diabetes (type 2), cancer of the colon and breasts, heart attacks, and strokes c) Researchers have discovered several of the mechanisms that help regulate body weight © 2015 Pearson Education Ltd  Appetite-regulating hormones ghrelin (stomach wall) o triggers feelings of hunger as meal times approach leptin (adipose tissue) - suppresses appetite PYY (small intestine) o after meals o appetite suppressant; counters ghrelin insulin (pancreas) o a rise in blood sugar level after a meal o suppresses appetite by acting on the brain © 2015 Pearson Education Ltd  Nutritional Requirements A nutritionally adequate diet satisfies three needs: o fuel (chemical energy) for all the cellular work of the body o organic raw materials animals use in biosynthesis (carbon skeletons to make many of their own molecules) o essential nutrients (materials that an animal’s cells require but cannot synthesize; obtained from dietary sources) © 2015 Pearson Education Ltd  Essential Nutrients 1. Essential amino acids animals require 20 amino acids to make proteins must be obtained from food in prefabricated form o eight amino acids are essential in the adult human (phenylalanine, lysine, isoleucine, leucine, valine, methionine, tryptophan, and threonine) with histidine and arginine essential for normal growth of children © 2015 Pearson Education Ltd  Essential Nutrients protein deficiency from a vegetarian diet can be avoided by eating a combination of plant foods that complement each other to supply all essential amino acids © 2015 Pearson Education Ltd  Essential Nutrients 2. Essential fatty acids unsaturated seeds, grains, vegetables © 2015 Pearson Education Ltd  Essential Nutrients 3. Vitamins are organic molecules required in the diet in small quantities 13 vitamins essential to humans have been identified water-soluble vitamins generally function as co- enzymes © 2015 Pearson Education Ltd © 2015 Copyright © 2002 Pearson Education Ltd Pearson Education, Inc., publishing as Benjamin Cummings © 2015 Copyright © 2002 Pearson Education Ltd Pearson Education, Inc., publishing as Benjamin Cummings  Essential Nutrients 4. Minerals are simple inorganic nutrients, usually required in small amounts humans and other vertebrates require large quantities of calcium and phosphorus for the construction and maintenance of bone iron is a component of the cytochromes and of hemoglobin while sodium, potassium, and chloride have a major influence on the osmotic balance between cells and the interstitial fluids, excess consumption of salt (sodium chloride) is harmful © 2015 Pearson Education Ltd © 2015 Pearson Education Ltd  Hormones and Hunger in mammals, a hormone called leptin, produced by adipose cells, is a key player in a complex feedback mechanism regulating fat storage and use © 2015 Pearson Education Ltd MSG-mouse an animal model for non-alcoholic steatohepatitis Nonalcoholic fatty liver disease (NAFLD) NAFLD is the most common cause of chronic liver disease with a prevalence of 25%. The spectrum of NAFLD includes fatty liver (NAFL) and steatohepatitis (NASH) which may progress to fibrosis and eventually cirrhosis. It shares the major lifestyle-related causative factors with obesity, and type 2 diabetes (insulin resistance). Is considered to be the hepatic component of metabolic syndrome. The classic NAFLD patient has persistently elevated liver enzymes (aspartate aminotransferase -AST and alanine aminotransferase - ALT). Clinical impact of NAFLD The prevalence of NAFLD in Japan: 14-21% NASH in NAFLD: 15% 10 years - Cirrhosis 20% Death 3% Clark. J.M., et al. Gastroenterology 2002; 122:1649-1657 ⚫Free fatty acids Two-hit theory ⚫TNF ⚫Other peptide mediators ⚫Genetic predisposition Nonalcoholic fatty Insulin resistance Other factors liver - which organ? mutations (e.g. apoB, MTTP) ⚫ ⚫deficiencies (e.g. choline) 1st hit Reversible - which signaling ⚫excess carbohydrates (e.g. TPN) pathway? ⚫drugs (e.g. tamoxifen) Fat accumulation ⚫toxins (e.g. hydrocarbons) (NAFL) Irreversible 2nd hit oxidative stress Nonalcoholic steatohepatitis Cell injury (steatohepatitis) (NASH) ⚫genetic polymorphisms? ⚫environmental or dietary factors? Inflammation Fibrosis/cirrhosis Morphologic changes e.g. ballooning, Mallory bodies Liver cirrhosis Neuschwander-Tetri, B.A. and Caldwell, S.H. Hepatology 2003; 37:1202-1219 HCC  Typical NASH histopathology Micro/macro-vesicular fatty change Ballooning Neutrophil aggregation Mallory body  Monosodium Glutamate (MSG) Glutamate occurs naturally in protein-containing foods , produced by the human body and is vital for metabolism and brain function. MSG - sodium salt of glutamic acid/glutamate. Used as a food additive and is a flavour enhancer. Current average daily intake is 10g/day – supported by MSG optimal safety profile. Toxic effects described in human adults, as manifested by the MSG symptom complex (Chinese restaurant  Could impair memory retention and induce damage in the hypothalamic neurons in mice. Alteration in lipid peroxidation and antioxidant status in different brain regions, (cerebral hemispheres, cerebellum, brain stem and diencephalons). Alteration in the levels of carbohydrates, lipid and proteins in rats treated with MSG. Animal models – based on genetic defects (gal-3 KO mouse), or diet-induced (high fat/cholesterol diet).  Monosodium glutamate (MSG) mouse model Animal: Mouse - Crj:CD-1(ICR) Treatment: MSG (2mg/g) was injected for five consecutive days (0～4 postnatal) Nagata M, et al. Exp Anim. 55(2), 109- 115, 2006 © 2015 Pearson Education Ltd  Materials © 2015 Pearson Education Ltd  Materials © 2015 Pearson Education Ltd  MSG-mouse (6-month-old) Control F MSG-F Control M MSG-M Central obesity Obesity and diabetes mellitus Higher incidence (70%) in male mice © 2015 Pearson Education Ltd  MSG-mouse female - 138.8% increased at 29 wks MSG-mouse MALE – 118.3% increased at 29 wks © 2015 Pearson Education Ltd Nagata M, et al. Exp Anim. 55(2), 109-115, 2006  Higher blood glucose level of MSG-mouse male – decrease in glucose tolerance Higher glucose reduction in MSG- mouse male – insulin resistance © 2015 Pearson Education Ltd Nagata M, et al. Exp Anim. 55(2), 109-115, 2006  Blood concentration levels of MSG-mouse were higher than in control Nagata M, et al. Exp Anim. 55(2), 109-115, 2006 © 2015 Pearson Education Ltd  Organ weights of MSG-mice were heavier than in control. Nagata M, et al. Exp Anim. 55(2), 109-115, 2006 © 2015 Pearson Education Ltd  SUMMARY Body mass index of MSG-mouse is higher than control. No polyphagia or polydipsia was observed indicating that obesity was not caused by polyphagia but due to the amount and frequency of MSG injection. High rate (70%) of glycosuria (increased glucose level in the plasma), decrase in glucose tolerance and appearance of insulin resistance in MSG-mouse males. Confirming that MSG-mouse males develop obesity without polyphagia and Type 2 diabetes mellitus. © 2015 Pearson Education Ltd  Control mice M (6 mos.) F (6 mos.) ×200 ×200 M (12 mos.) F (12 mos.) ×200 ×200 © 2015 Pearson Education Ltd  NAFLD-like change (MSG-mouse 6M ♂) Microvesicular fatty change CV P ×100 CV: central vein P: portal tract Ballooning ×400 © 2015 Pearson Education Ltd  NASH-like change (MSG-mouse 12M ♂) Micro- and macrovesicular fatty change Portal inflammation ×100 ×200 Mallory body ×400 Neutrophil aggregation © 2015 Pearson Education Ltd  Sudan IV staining C-M (6 mos.) CV P C V P MSG- M (12 mos.) MSG- M (6 mos.) CV: central vein P: portal tract © 2015 Pearson Education Ltd  Azan staining CV: central vein P: portal tract C- M (6 MSG- M mos.) (6 mos.) P C ×200 ×200 V MSG- M MSG- M (12 mos.) (12 mos.) C V Pericellular and ×200 ×400 perivenular fibrosis © 2015 Pearson Education Ltd  NAFLD-like features (6-month-old) P