Human Form & Function 2. Exocrine Secretory Functions of The Liver and Pancreas. Dr. Neil Docherty

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1 Human Form & Function 2 Exocrine Secretory Functions of The Liver and Pancreas Dr. Neil Docherty

2 Teaching Objec5ves Describe the structure of the exocrine pancreas and identify the major acinar and ductular secretions Discuss key aspects of the cellular physiology of exocrine pancreatic secretion Describe the lobular structure of the liver and the fundamental aspects of bile production, storage and recirculation, and its role in digestion and absorption. Highlight the causes of choleostasis and its consequences for the digestive and absorptive processes.

3 The Sphincter of Oddi Delivers Pancreatic and Biliary Secretions to the Duodenum Sphincter of Oddi EXOCRINE PANCREATIC SECRETIONS 1)Ductular -Bicarbonate solution 2) Acinar -Enzyme rich secretion Duodenal Cluster Unit ACINAR SECRETIONS REACH DUCTS AND ARE CARRIED TOWARDS THE DUODENUM WHERE THEY ARE DELIVERED ALONG WITH BILE

4 Basics of Pancreatic Secretion ACINUS INTERCALATED DUCT Enzymes /zymogens H 2 O HCO3 - ALKALINE ENZYME MIX

5 Acinar Cell Secretions Digestive enzymes Stored as granules Released by regulated compound exocytosis PROTEASES AMYLOLYTICS LIPASES NUCLEASES OTHERS Trypsinogen Amylase Lipase DNase Procolipase Chymotrypsinogen Esterase RNase Trypsin inhibitor Proelastase Phospholipase A 2 Procarboxypeptidase A Procarboxypeptidase B

6 Regulated Exocytosis Pancreatic Acinar Cells Lumen of Acinus T.E.M. of Pancreatic Acinar Cell

7 Route from Acini to Duodenum Acini Intercalated ducts Intralobular duct Interlobular duct Main pancreatic duct (Wirsung s duct) Accessory pancreatic duct (Duct of Santorini) Common bile duct Sphincter of Oddi Duodenal Ampulla

8 Ductular Cell Secretions Secrete bicarbonate in response tp secretin Water follows paracellularly PROVIDES FOR ACID NEUTRALISATION AIDS IN ESTABLISHING ph OPTIMUM FOR PANCREATIC ENZYME ACTIVITY

9 Secre5n and Cholecystokinin (CCK)

10 CCK-More Detail on Effect on Pancreas Fat and protein in duodenal lumen CCK releasing peptide release Duodenal I cells CCK Ductular cells Direct endocrine and vago-vagal Acinar cells Potentiation of bicarbonate release Enzyme secretion N.B. As levels of active trypsin elevate in gut lumen, proteolytic cleavage of releasing peptide Release ensues (negative feedback control)

11 Secretin-More Detail Gastric acid in duodenum Potentiation of bicarbonate release Duodenal S cells Elevation in ph shuts down secretin release SECRETIN RELEASE Bloodstream Acid neutraliztion and enzyme activation in duodenum Stimulation of pancreatic ductular secretion of bicarbonate

12 Mutant gene code In Cystic Fibrosis Cellular Physiology of Ductular Bicarbonate Secretion Ductular Epithelium D U C T L U M E N Cl - HCO 3 - Cl - Cl - /HCO 3 - exchange CFTR HCO 3 phosphorylation H 2 O + CO 2 PKA Carbonic anhydrase II H camp Na + HCO 3-2K + K + Na + / HCO 3 - Na + Na + Na + / K + ATPase 3Na + Na + / H + H + K+ channel K + H 2 O Transepithelial osmotic gradient DILUTE ALKALINE SECRETION SECRETIN

13 Cystic Fibrosis Ireland has highest incidence in World Mutations in CFTR chloride channel gene Although lung disease most widely known correlate, named for characteristic pancreatic lesions Inability to secrete bicarbonate from pancreas Pancreas is not flushed. In duodenum, acid remains unneutralised and pancreatic enzymes remain inactive. In severe homozygous mutations, exocrine pancreas destroyed during foetal life Pancreatic insufficiency=antacid and enzyme supplements

14 Liver Largest and most important metabolic organ in the body -metabolic processing of nutrient -detoxification and biotransformation for excretion -metabolic activation -Synthesis of plasma proteins -Immune function -Storage of minerals and vitamins -Production of bile Relevant to excretory, digestive and absorptive function

15 Destination of Absorbed Materials 3 circulations meet and mingle TAGs Via lymphatics And thoracic duct Glucose Amino acids SCFAs Soluble vitamins

16 Lobular Structure of Liver

17 Bile Principal Components -bile acids, -cholesterol -phosphotidylcholine -conjugated bilirubin Fat dispersal Mixed micelle formation digestion and absorption

18 Bile acids ( mg/day) HEPATOCYTES HIGH WATER SOLUBILITY LOW WATER SOLUBILITY INTESTINAL BACTERIA

19 Bile Acid Conjugation and Deconjugation In hepatocyte Glycine and taurine conjugation of primary and secondary bile acids-increases solubility Bacterial deconjugation -Decreases solubility

20 Bile Processing on Journey Through Liver Canaliculi Hyperosmotic secretion, addition of calcium, phosphotidylcholine and cholesterol Ductules glucose and amino acid reabsorption, addition of bicarbonate, free water and secretory IgA. Renders isotonic alkaline solution Ducts Addition of mucus

21 The Gall Bladder Bile Storage and Mobilisation Bile Related Effects of CCK -Gall bladder contraction -Sphincter of Oddi Relaxation

22 Micelle Formation (RE: Lipid Absorption) Allows for trapping of lipid soluble compounds in intestine

23 Enterohepatic Recirculation of Bile Acids Apical Sodium Dependent Bile Acid Transporter (ASBAT) Kidney mg produced per day However, During feeding, mg/h

24 Cholestasis Production and/or excretion of bile impaired Causes Primary biliary cirrhosis Primary Sclerosing Cholangitis Consequences Hereditary Cholestasis Syndromes pruritis, hypercholesterolaemia, Malabsorption, hepatic fibrosis Obstructive Jaundice

25 Your Learning From Today Should focus on being able to; 1) Describe the structure of the exocrine pancreas and identify the major acinar and ductular secretions 2) Discuss key aspects of the cellular physiology of exocrine pancreatic secretion and the consequences and causes of insufficiency 3) Describe the role of the liver in digestion and absorption 4) List common causes of choleostasis and describe its consequences for the digestive and absorptive processes.

THE DIGESTIVE SYSTEM Secretion Graphics are used with permission of: Pearson Education Inc., publishing as Benjamin Cummings (http://www.aw-bc.

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