BHS 116.2 – Physiology Notetaker: Vivien Yip Date: 1/23/2013, 1st hour Page1 Clicker Q True or false, aceylcholine inhibits gastrin secretion False Acetylcholine is parasympathetic stimulation and stimulates digestion Question dropped from test Adrenal Cushing syndrome ocular symptoms - Least likely to occur: o Glaucoma o Diplopia o Cataracts o Retinopathy Inhibit glucose uptake, hyperglycemia is major symptom Hypertension in addition to hyperglycemia Will get retinopathy and cataracts Could possibly get diplopia with fat distribution in the eye Trigger neuronal defects resulting in EOM palsies and diplopia (reason why it is dropped) Lecture 15 GI Secretory Functions continued and absorption in the GI tract Describe the various secretions of the GI tract as well as their functions and regulations – pancreas, liver, small intestine, large intestine Pancreatic secretion - CHO digestion w/ salivary amylase - Begin some protein digestion with pepsin in the stomach - But minimal digestion of nutrients up to this point - Pancreas play major role in changing that o Secrete vast majority of enzymes that will break down the nutrient components - Endocrine function o Islets: insulin and glucagon - Exocrine function o Acinar cells Glandular cells Release a number of digestive enzymes to break down CHO (carbohydrates), PRO (protein), fats o Ductal cells Leave to the ducts and release contents Release sodium bicarbonate and neutralize acidic chyme - Each cell type produce very important things in digestive process Pancreatic Secretion - List of major enzymes released from exocrine portion of pancreas - Released in their inactive form (-ogen) o Trypsinogen Digests proteins into peptides o Chymotrypsinogen Digests proteins into peptides o Procarboxypeptidase Digests peptides into amino acids o Pancreatic amylase Digests carbohydrates into disaccharides o Pancreatic lipase Primary lipid enzyme Digests fat (TG) into fatty acids and monoglycerides o BHS 116.2 – Physiology Notetaker: Vivien Yip Date: 1/23/2013, 1st hour Page2 o Cholesterol esterase Hydrolyzes cholesterol esters o Phospholipase Digests phospholipids into fatty acids - Proteolytic enzymes are secreted in their inactive forms - Also trypsin inhibitor released with them to help prevent activation of trypsinogen until it gets to GI tract - Small enzyme on duodenal epithelial cells called enterokinase o Once these proteases enter the duodenum, the enterokinase will convert trypsinogen into active trypsin o Trypsin is now formed, it will convert procarboxypeptidase to carboxypeptidase and chymotrypsinogen to chymotrypsin o Now all proteases are active - Lipase is active already - Pancreatic amylase is already active when secreted - Ductal epithelial cells will release bicarbonate to increase the pH and reduce acidity of chyme o Enzymes work much better when pH is neutralized Regulation of pancreatic secretion - Neuronal (from vagus) o Acetylcholine (parasympathetic nerves) - Hormonal o CCK When food enters the duodenum, this is secreted Cause acinar cells to release enzymes o Secretin Response to acid in duodenum Activate ductal epithelial cells to release sodium bicarbonate to reduce acidity of chime - Acid in duodenum causes secretin release Fat and protein cause CCK release CCK will cause acinar cells to release enzymes to break down those components Secretion of bile by the liver - Produced by the liver - 2 important functions o Primary aids in fat digestion, without bile present, we would have very inefficient digestion of lipids Emulsify fat particles into smaller particles o Role in absorption aiding the transfer of fats into the intestinal epithelium once they are broken down - Also functions to get rid of waste products and cholesterol Bile is continuously made in the liver - Continuously secreted - If no digestion occurring, no chyme in small intestine, bile will go into gallbladder and stored until it is needed - No active digestion, bile is still continuously secreted by the liver BHS 116.2 – Physiology Notetaker: Vivien Yip - Date: 1/23/2013, 1st hour Page3 (hormonal regulation) CCK stimulates the gallbladder to contract and release bile into the small intestine (neuronal regulation) Acetylcholine causes gall bladder contraction Secretions of Small intestines - Primarily mucous, water - First part of duodenum: Brunner’s gland o Where chyme is most acidic, just came from stomach o Some sodium bicarb from pancreas to neutralize that o Secrete alkaline mucus protects epithelium, both from acid and the proteases help neutralize pH o Mucus is released just in response to tactile stimuli As soon as chyme is released Physical pressure on the epithelial cells Aided by vagus innervation CCK and secretin also help with stimulating alkaline mucus secretion o Sympathetic stimulation inhibits this process - Further down intestine: Crypts of Leiberkuhn o Small valleys throughout entire length of small intestines o Goblet cells secrete mucus o More of a protective mechanism to help movement of chyme through small intestines o Enterocytes, main epithelial cell Secrete and absorb water and electrolytes about 2L/day - Regulated by neuronal and hormonal influences (CCK and secretin) - Non secretory function o Small digestive enzymes physically attached to surface of enterocytes o Not secreted, membrane bound Break down anything that is left over from the other enzymes Peptidase (peptides amino acids) Sucrose, maltase, isomaltase, lactase (disaccharides monosaccharides) Intestinal lipase (fats glycerol + FA) Secretion of the Large Intestine - Only really secretes mucus to protect epithelial lining and help movement of chyme Describe the digestion process for CHO, PRO, fats and their absorption by the GI epithelium – enzymes, bile, transport into and out of epithelium Digestion of CHO - Digestion starts in mouth w/ salivary amylase - Only 3 major sources of CHO in the normal human diet o Starches (large polysaccharides) Salivary amylase will break it down into maltose Any of the larger polysaccharides will be broken down by pancreatic amylase o Lactose (disaccharide in milk) o Sucrose (disaccharide, cane sugar) - CHO are broken down into monosaccharides after disaccharides - 3 monosaccharides o Glucose o Galactose o Fructose These are the only ones absorbed in GI tract - Digestion begins in the mouth w/ salivary amylase (enzyme ptyalin) - Continues in esophagus and for a brief time in stomach until the acid inhibits function of the amylase - CHO digestion finishes in the duodenum of the small intestines BHS 116.2 – Physiology Notetaker: Vivien Yip Date: 1/23/2013, 1st hour Page4 o - Disaccharides then are broken down into monosaccharides by the enzymes that are attached to the surface of the enterocytes Maltase, lactase, sucrose (on surface of enterocytes), complete the last digestive reaction - - - o o o Starches, big polysaccharides broken down by pancreatic and salivary amylase into disaccharides Further broken down by lactase, sucrase and maltase found on the surface of the enterocytes into monosaccharides Glucose is found in one of the components in all of the disaccharides Maltose = gluc + gluc Lactose = galactose + gluc Fructose = sucrose + glucose Protein digestion does not start until it gets to the stomach - Starts w/ pepsin, requires HCl - Pepsinogen is what is secreted and needs the conversion to pepsin to begin that process - Only enzyme to break down collagen (component of muscle in meat) - Vast majority of protein digestion occurs in the pancreas o Pancreatic enzymes Break down into tripeptides, dipeptides, amino acids o Peptidase enzymes on surface of the enterocytes will carry out last process (lining the intestinal villi) Break down any peptides left over into amino acids Some dipeptides are taken up by the enterocytes, there is a peptidase inside the enterocytes that will break it down Vast majority of the peptides is broken down already at the surface of enterocytes - - - Most of the break down occurs via pepsin and pancreatic proteolytic enzymes Smaller peptides are further broken down to aminopeptidase on surface of enterocytes If some dipeptides get through, will have intracellular peptidase that will break down into individual amino acids BHS 116.2 – Physiology Notetaker: Vivien Yip Date: 1/23/2013, 1st hour Page5 Digestion of fats - More complicated process - Most abundant dietary fat is triglyceride - Do get a little digestion in the stomach – but is mechanical, not enzymatic - Just by force of stomach, can break larger fat particles into smaller fat particles - Essentially, all of fat digestion occurs in the small intestine - First step is emulsification of fat by breaking down the larger fat particles into smaller fat particles and getting them to be water soluble so lipase can physically break down and digest the fat particles - Mixing movements that occur with the small intestines, help physically break down - Bile also plays key role in emulsification process - Fat is not water soluble - Bile salt will bind to these water insoluble fat molecules and incorporate into the large fat particles into smaller fat particles - Bile salts are both lipid soluble and insoluble components, water soluble portion are exposed on outside, which makes the fat droplets water soluble - Now broken down to smaller parts, lipase can act on these surfaces Pancreatic lipase is the most important enzyme in fat digestion - Left over is fatty acid and glycerol - - Large fat particle, primarily triglycerides Bile salts help emulsify into smaller lipid particles so pancreatic lipase can act on it Lipase can break it down to glycerol and free fatty acids Bile salts will now bind to individual fatty acids and help solubilize those fats and allow them to be brought to surface of enterocytes so they can be broken down there o Aid in absorption Role in digestion Absorption in the stomach - Only a few highly lipid soluble substances are absorbed in the stomach (except for alcohol and aspirin) o No nutrient absorption in the stomach Describe the various folds and absorptive surfaces of the small intestines Vast majority of absorption occurs in the small intestines - Absorptive surface area of the small intestine is increased almost 1000 fold due to folding o Tremendous amount of absorptive area for nutrients released from enzymatic processes - Gross circular fold, can physically see - Next we have forming of villi, blood vessels and lymph vessels projecting - Enterocytes are all lining the villi - On the surface of each enterocytes are microvilli (brush border) o Finger like projections on the surface Describe the process of absorption of ions and in the GI tract Absorption of ions - Water is absorbed by osmosis into pericellular spaces (follows Na+) - Na+ is absorbed into the blood by diffusion into and between the enterocytes followed by active transport out of the enterocytes BHS 116.2 – Physiology Notetaker: Vivien Yip Date: 1/23/2013, 1st hour Page6 CHO absorption - All CHO are absorbed as monosaccharides o Glucose and galactose via sodium co-transport mechanism o Fructose is transported via facilitated diffusion mechanism and is converted into glucose in the epithelium (or in the liver) - Sodium is prevalent in the lumen, monosaccharides, glucose taken up through active transport - Fructose via GLUT 5 is (main transporter) for enterocytes– does not require insulin - Once those monosaccharides are inside the enterocytes, they need to be pumped out - Both fructose and glucose leave enterocytes via GLUT 2 - Taken up into the blood, carried to cells or liver to be stored Protein absorption - Taken up as individual amino acids or as di or tripeptides - This is a process of co transport with sodium - Sodium amino acid transporter in membrane of enterocytes - Same process as CHO - Small peptides taken up, intracellular peptidase will break it down into individual amino acids Only amino acids leave enterocytes to be taken up by the blood through facilitated diffusion High concentration inside the cell, facilitated diffusion out into the blood Fat absorption - Primarily taken up as monoglycerides and free fatty acids - Dissolved in bile micelles which makes them water soluble and can get down to villi and microvilli to diffuse into the cell - Diffuse directly through enterocyte membrane, lipid soluble - When they get inside the enterocyte, they are reconverted to triglycerides - Triglycerides packaged into chylomicrons o Chylomicrons contain triglycerides, cholesterol and protein - Chylomicrons have to undergo exocytosis to leave the cell - Do not enter blood o Capillaries cannot uptake chylomicrons (too large) and no receptors o Instead, they enter the lymph system Absorption in large intestine - Mostly water and electrolytes in the chyme are absorbed in the proximal half of the large intestines - Bacteria digests small amounts of cellulose - Bacteria can produce vitamins: o Vitamins K, B12, thiamine, Riboflavin Clicker Q Where does digestion of proteins begin? - Stomach