Lecture 15: Pancreas & Liver Fall 2024 PDF

1502 Pancreas & Liver Fall 2024 Lecture 15 Wednesday Sept. 25 - 9am Dr. L. Al-Nakkash [email protected] 1  Learning Objectives: Pancreas 1. Identify the differences between endo...

1502 Pancreas & Liver Fall 2024 Lecture 15 Wednesday Sept. 25 - 9am Dr. L. Al-Nakkash [email protected] 1  Learning Objectives: Pancreas 1. Identify the differences between endocrine & exocrine pancreas. 2. Describe how pancreatic exocrine function is regulated. 3. Identify the types of and roles of pancreatic proteolytic enzymes, pancreatic amylase, pancreatic lipase. 4. Describe pancreatic duct secretion. 5. Pancreatic pathophysiology: Cystic fibrosis 6. Examine the role of secretin on the pancreas. 7. Examine the role of CCK on the pancreas. © L. Al-Nakkash 2024 2  Pancreas Found throughout pancreatic tissue: Insulin, Glucagon Sherwood Fig. 16-11 © L. Al-Nakkash 2024 1. Identify the differences between endocrine & exocrine pancreas. 3  Pancreas & ANS Sympathetic Parasympathetic vagus inhibits stimulates Pancreatic secretion Pancreatic secretion Opposite effects!! Note: different to salivary secretion!! How? PNS & SNS BOTH stimulatory for salivary secretion © L. Al-Nakkash 2024 2. Describe how pancreatic exocrine function is regulated. 4  Pancreatic Enzymes Acinar cells secrete 3 types of pancreatic enzymes: – Pancreatic proteases – digest what food type? proteins Inactive - Trypsinogen, chymotrypsinogen & procarboxypeptidase Converted to their active forms in the duodenal lumen – Pancreatic α-amylase – digest what food type? carbohydrates Active – cleaves polysaccs into disaccs what other enzyme digests carbs? Salivary amylase – Pancreatic lipase – digest what food type? fats – Active – hydrolyzes dietary TG into MG +2FA 5 © L. Al-Nakkash 2024 3. Identify the types of and roles of pancreatic proteolytic enzymes, pancreatic amylase, pancreatic lipase.  Pancreatic Proteolytic Enzymes From duodenal mucosal cells inactive active trypsinogen enteropeptidase trypsin enterokinase What other enzyme is similar to trypsinogen? pepsinogen inactive active Chymotrypsinogen + trypsin Chymotrypsin + Procarboxypeptidase carboxypeptidase In duodenum lumen 6 © L. Al-Nakkash 2024 3. Identify the types of and roles of pancreatic proteolytic enzymes, pancreatic amylase, pancreatic lipase.  Pancreatic Aqueous Alkaline Secretion Pancreatic enzymes – function best in slightly alkaline environment. Acidic chyme emptied into duodenum – Must be neutralized quickly: 1. It allows optimal functioning of pancreatic enzymes 2. It prevents acidic damage to duodenal wall What is acid chyme neutralized by? NaHCO3-rich fluid secreted by the pancreas into the duodenum This aqueous NaHCO3 component is the largest part of pancreatic secretion. 3. Identify the types of and roles of pancreatic proteolytic enzymes, pancreatic amylase, pancreatic lipase. 7 © L. Al-Nakkash 2024 4. Describe pancreatic duct secretion.  Pancreatic Aqueous Alkaline Secretion CFTR CF chlorideCl- Na+ channel K+ 2Cl- CF H2O Net secretion of HCO3 Net absorption of H+ Costanzo How is this different to salivary secretions? Isotonic, hypotonic 8 © L. Al-Nakkash 2024 4. Describe pancreatic duct secretion.  Cystic Fibrosis Thickened secretions build up in pancreatic ducts→leads to inability of pancreatic enzymes to get into the duodenum. cause of pancreatic exocrine failure in children Insufficient pancreatic digestive enzymes released. How would this affect food digestion? It is incomplete Pancreas is a major source of lipase. – With pancreatic enzyme deficiency → fats maldigested. Would digestion of protein & carbs be equally affected? NO. Salivary, Gastric, SI enzymes → contribute towards their digestion. CF symptoms; – Steatorrhea Excess undigested fat excreted in feces Stools are greasy, odorous & float. – Poor weight gain Require Pancreatic enzyme supplements What about the ability to absorb Vits A,D,E & K? ↓ Why? All fat-soluble vitamins 9 © L. Al-Nakkash 2024 5. Pancreatic pathophysiology: Cystic fibrosis  Pancreatic Exocrine Secretion Regulated by CCK & Secretin Pancreatic exocrine secretion – mainly regulated by hormonal control. Major stimulation of pancreatic secretion – During the intestinal phase of digestion As chyme enters the SI. Pancreatic secretion is stimulated 2 major enterogastrones are released: – Secretin and cholecystokinin, CCK 10 © L. Al-Nakkash 2024 6. Examine the role of secretin on the pancreas. 7. Examine the role of CCK on the pancreas.  Regulation of Pancreatic Secretion S cells I cells Sherwood Fig. 16-12 11 © L. Al-Nakkash 2024 6. Examine the role of secretin on the pancreas. 7. Examine the role of CCK on the pancreas. Enzyme secretion from pancreatic acinar cells Gastrin released during cephalic and gastric phases Most important pathway Gastrin-releasing peptide=Bombesin Secretin/CCK released during intestinal phase Inhibitory 12 © L. Al-Nakkash 2024 6. Examine the role of secretin on the pancreas. 7. Examine the role of CCK on the pancreas.  Learning Objectives: Liver 1. Identify the basic structure & functions of the liver. 2. Identify the composition of bile salts 3. Examine the role of bile salts and the enterohepatic circulation. 4. Describe the importance of bile salts to aid fat digestion. 5. Assess what bilirubin is. 6. Liver Pathophysiology: Cirrhosis. 13 © L. Al-Nakkash 2024  A gatekeeper: Storage -processes useful substances -detoxifying orally ingested Glycogen, fat, proteins, vitamins harmful products Produce cellular fuel Removal Glucose, FA Bacteria/ old RBC It supports a high rate of oxidation of fatty acids →energy source. Detoxification Secrete drugs Liver functions Bile salts Mostly served by Kupffer cells (phagocytes) Synthesis Excretion plasma proteins bilirubin & clotting factors Activation i.e. Prothrombin. vitamin D 14 © L. Al-Nakkash 2024 1. Identify the basic structure & functions of the liver.  Liver functional units are lobules. Lobule = hexagonal tissue surrounding a central vein Outer edge has 3 vessels Portal triad 15 © L. Al-Nakkash 2024 1. Identify the basic structure & functions of the liver.  Bile Salts Bile, consists of: – Aqueous alkaline fluid – continuously secreted by hepatocytes – organic constituents: M ajor bile salts constituents Phospholipids Cholesterol Bilirubin Electrolytes water 16 © L. Al-Nakkash 2024 2. Identify the composition of bile salts  Bile Salts Bile salts are: 1. derivatives of cholesterol. Bile salt = a bile acid Conjugated with AA’s taurine or glycine 2. actively secreted into bile. 3. reabsorbed into blood via active transport mechanisms in the terminal ileum – (after participating in fat dig & abs). 4. returned to liver via hepatic portal system. – resecretes them into bile – This daily recycling of bile salts between the SI and liver what circulatory system is this known as? Enterohepatic circulation 17 © L. Al-Nakkash 2024 3. Examine the role of bile salts and the enterohepatic circulation.  When chyme enters SI Intestinal phase Costanzo ↑ gallbladder emptying Chyme in SI CCK released BI LE STORAGE relaxes Bile salts emulsify fats: Lipid absorption Enterohepatic circulation Na+-bile cotransport When lipid absorption complete: bile salts recirculated back to liver This reduces the demand to synthesize new bile salts 18 © L. Al-Nakkash 2024 3. Examine the role of bile salts and the enterohepatic circulation. Bile Salts Aid Fat Digestion & Absorption Bile salts have a detergent action: Bile salts convert fat globules into a lipid emulsion – consists of many fat droplets suspended in aqueous chyme What will this do to the available area for attack by pancreatic lipase? Increased 19 © L. Al-Nakkash 2024 4. Describe the importance of bile salts to aid fat digestion  Micelles Bile salts facilitate fat absorption - by micelle formation. Micelles; bile salts & lecithin aggregate in clusters. Products of fat digestion can now be transported through lumen to absorptive surface of SI Amphipathic= hydrophilic + hydrophobic regions 20 © L. Al-Nakkash 2024 4. Describe the importance of bile salts to aid fat digestion  Bilirubin Another constituent of bile Yellow pigment Waste product Not involved in digestion Excreted in bile From degradation of heme part of hemoglobin in RBC. – hepatocytes take up bilirubin, modify it to increase solubility & excrete it into bile. In the intestines, bacterial enzymes modify bilirubin, and this yields a normal fecal color. If bile secretions are blocked will fecal color change? Yes, a more gray fecal color In addition, small amounts of bilirubin are reabsorbed from the intestines & excreted in urine Gives urine the typical color 21 © L. Al-Nakkash 2024 5. Assess what bilirubin is.  Cirrhosis – Prolonged hepatic inflammation. Usually associated with intake of ? ALCOHOL > 60% of cases in US – Damaged hepatocytes are replaced by connective tissue and collagen deposition, which will ↓ active liver tissue → chronic liver failure. – Symptoms: jaundice, weight-loss, abdominal pain, abdominal ascites Fluid retention – Treatment: No alcohol, diuretics, antibiotics https://www.verywellhealth.com/cirrhosis-what-you-need-to-know-1759889 22 © L. Al-Nakkash 2024 6. Liver Pathophysiology: Cirrhosis.  Both the PNS and SNS stimulate pancreatic secretions True / False All pancreatic proteases are secreted in their active form True / False K cells in the duodenal mucosa release CCK True / False CCK acts on acinar cells & increases enzyme release True / False The liver has 2 outer edge vessels True / False Bile salt release can be increased by CCK True/False Micelles help carry products of protein digestion True/False 23 © L. Al-Nakkash 2024  Both the PNS and SNS stimulate pancreatic secretions True / False PNS stimulates SNS inhibits All pancreatic proteases are secreted in their active form True / False All Inactive: trypsinogen, chymotrypsinogen, procarboxypeptidase K cells in the duodenal mucosa release CCK True / False I cells release CCK CCK acts on acinar cells & increases enzyme release True / False ↑ enzyme release Mediated by ↑ IP3 & Ca 2+ The liver has 2 outer edge vessels True / False 3: hepatic artery, hepatic portal vein, bile duct Bile salt release can be increased by CCK True/False Yes; this causes release of Bile salts from the gallbladder Micelles help carry products of protein digestion True/False Fat digestion: cholesterol 24 © L. Al-Nakkash 2024