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• Microscopic anatomy of the liver (cont.) – Hepatocytes have increased rough and smooth ER, Golgi apparatus, peroxisomes, and mitochondria – Hepatocyte functions • Produce ~900 ml bile per day • Process bloodborne nutrients – Example: store glucose as glycogen and make plasma proteins • Store fat-soluble vitamins • Perform detoxification – Example: converting ammonia to urea • Bile: Composition and enterohepatic circulation – Yellow-green, alkaline solution containing: • Bile salts: cholesterol derivatives that function in fat emulsification and absorption • Bilirubin: pigment formed from heme – Bacteria break down in intestine to stercobilin that gives brown color of feces • Cholesterol, triglycerides, phospholipids, and electrolytes – Enterohepatic circulation • Recycling mechanism that conserves bile salts • Bile salts are: – Reabsorbed into blood by ileum (the last part of small intestine) – Returned to liver via hepatic portal blood – Resecreted in newly formed bile • About 95% of secreted bile salts are recycled, so only 5% is newly synthesized each time • Composition of pancreatic juice – 1200–1500 ml/day is produced containing: • Watery, alkaline solution (pH 8) to neutralize acidic chyme coming from stomach • Electrolytes, primarily HCO3− • Digestive enzymes – Proteases (for proteins): secreted in inactive form to prevent self-digestion – Amylase (for carbohydrates) – Lipases (for lipids) – Nucleases (for nucleic acids) – Proteases are secreted in an inactive form; they are activated after they reach duodenum • Enteropeptidase, enzyme bound to plasma membrane of duodenal epithelial cells, activates pancreatic protease trypsinogen to trypsin • Once trypsin is activated, it can then activate: – More trypsinogen – Procarboxypeptidase to active carboxypeptidase – Chymotrypsinogen to active chymotrypsin • Bile duct and pancreatic duct unite in wall of duodenum – Fuse together in bulblike structure called hepatopancreatic ampulla • Ampulla opens into duodenum via volcano-shaped major duodenal papilla • Hepatopancreatic sphincter controls entry of bile and pancreatic juice into duodenum • Accessory pancreatic duct: smaller duct that empties directly into duodenum • Regulation of bile and pancreatic secretions – Bile and pancreatic juice secretions are both stimulated by neural and hormonal controls – Hormonal controls include: • Cholecystokinin (CCK) • Secretin • -Bile secretion is increased when: • Enterohepatic circulation returns large amounts of bile salts • Secretin, from intestinal cells exposed to HCl and fatty chyme, stimulates gallbladder to release bile • Hepatopancreatic sphincter is closed, unless digestion is active • Bile is stored in gallbladder and released to small intestine only with contraction Small intestine is the major organ of digestion and absorption • 2–4 m long (7–13 ft) from pyloric sphincter to ileocecal valve, point at which it joins large intestine • Small diameter of 2.5–4 cm (1.0–1.6 inches) • Blood supply: • Superior mesenteric artery brings blood supply • Veins (carrying nutrient-rich blood) drain into superior mesenteric veins, then into hepatic portal vein, and finally into liver • Nerve supply • Parasympathetic innervation via vagus nerve, and sympathetic innervation from thoracic splanchnic nerves • Blood supply: • Superior mesenteric artery brings blood supply • Veins (carrying nutrient-rich blood) drain into superior mesenteric veins, then into hepatic portal vein, and finally into liver • Nerve supply • Parasympathetic innervation via vagus nerve, and sympathetic innervation from thoracic splanchnic nerves • Modifications of small intestine for absorption • Small intestine’s length and other structural modifications provide huge surface area for nutrient absorption • Surface area is increased 600 to ~200 m2 (size of a tennis court) • Modifications include: • Circular folds • Villi • Microvilli • Histology of the small intestine wall (cont.) • Goblet cells: mucus-secreting cells found in epithelia of villi and crypts • Enteroendocrine cells: source of enterogastrones (examples: CCK and secretin) • Found scattered in villi but some in crypts • Paneth cells: found deep in crypts, specialized secretory cells that fortify small intestine’s defenses • Secrete antimicrobial agents (defensins and lysozyme) that can destroy bacteria • Stem cells that continuously divide to produce other cell types • Villus epithelium renewed every 2–4 days • Ileocecal valve control • Ileocecal sphincter relaxes and admits chyme into large intestine when: • Gastroileal reflex enhances force of segmentation in ileum • Gastrin increases motility of ileum • Ileocecal valve flaps close when chyme exerts backward pressure • Prevents regurgitation into ileum • Large intestine contains thicker mucosa made up of simple columnar epithelium • Except in anal canal, where it becomes stratified squamous epithelium to withstand abrasion • Does not contain circular folds, villi, or digestive secretions • Contains abundant deep crypts with many mucus-producing goblet cells • Mucosa of anal canal hangs in long ridges or folds referred to as anal columns • Anal recesses: located between anal columns; secrete mucus to aid in emptying • Pectinate line: horizontal line that parallels anal sinuses • Visceral sensory nerves innervate area superior to this line • Region insensitive to pain • Somatic nerves innervate inferior to this line • Region sensitive to pain • Superficial venous plexuses of anal canal form hemorrhoids if inflamed • Bacterial flora: consist of 1000+ different types of bacteria • Outnumber our own cells 10 to 1 • Enter from small intestine or anus to colonize colon • Metabolic functions • Fermentation • Ferment indigestible carbohydrates and mucin • Release irritating acids and gases (~500 ml/day) – Vitamin synthesis • Synthesize B complex and some vitamin K needed by liver to produce clotting factors • Keeping pathogenic bacteria in check – Beneficial bacteria outnumber and suppress pathogenic bacteria – Immune system destroys any bacteria that try to breach mucosal barrier • Epithelial cells recruit dendritic cells to mucosa to sample microbial antigens and present to T cells of MALT, triggering production of IgA that restricts microbes • Residue remains in large intestine 12–24 hours • No food breakdown occurs except what enteric bacteria digest • Vitamins (made by bacterial flora), water, and electrolytes (especially Na+ and Cl−) are reclaimed • Major functions of large intestine is propulsion of feces to anus and defecation • Motility of the large intestine – Haustral contractions: most contractions of colon, where haustra sequentially contract in response to distension • Slow segmenting movements, mostly in ascending and transverse colon – Gastrocolic reflex: initiated by presence of food in stomach • Results in mass movements: slow, powerful peristaltic waves that are activated three to four times per day – Descending colon and sigmoid colon act as storage reservoir Digestion of Carbohydrates • Only monosaccharides can be absorbed • Starch and disaccharides are broken down to oligosaccharides and disaccharides – Begins in mouth with salivary amylase • Further broken down into lactose, maltose, and sucrose • Final breakdown into monosaccarides (glucose, fructose, galactose) • Steps in lipid digestion in intestine – Emulsification: triglycerides and their breakdown products are insoluble in water • Need pre-treatment with bile salts that break large fat globules into smaller ones – Digestion: pancreatic lipases break down fat into monoglyceride plus two free fatty acids – Micelle formation: products from digestion become coated with bile salts and lecithin – Diffusion: lipid products leave micelles and cross epithelial membrane via diffusion • Steps in lipid digestion in intestine (cont.) – Chylomicron formation: lipid products are converted back into triglycerides and packaged with lecithin and lipoproteins, forming chylomicron – Chylomicron transport: chylomicrons are exocytosed from basolateral side and enter lymphatic lacteal • Eventually emptied into venous blood at thoracic duct • Once in blood, chylomicrons are broken into free fatty acids and glycerol by lipoprotein lipase so they can be used by cells • Short-chain fatty acids can diffuse directly into blood • Vitamin absorption – In small intestine • Fat-soluble vitamins (A, D, E, and K) are carried by micelles; diffuse into absorptive cells • Water-soluble vitamins (C and B) are absorbed by diffusion or by passive or active transporters • Vitamin B12 (large, charged molecule) binds with intrinsic factor and is absorbed by endocytosis – In large intestine: vitamin K and B vitamins from bacterial metabolism are absorbed • Malabsorption can be caused by anything that interferes with delivery of bile or pancreatic juice – Damaged intestinal mucosa (e.g., from bacterial infection or some antibiotics) • Gluten-sensitive enteropathy (celiac disease): common malabsorption disease – Immune reaction to gluten – Gluten causes immune cell damage to intestinal villi and brush border – Treatment: eliminate gluten from diet