Physiology lecture 28

Pancreas and bile

gross anatomy of GI system

Gross anatomy​ in liver

Pancreatic exocrine secretion​ to know

• Functions​

• Mechanisms of secretion​

• Control

Organisation of Pancreas​

Pancreatic juice​

• Enzymes​ - Digestion, Pancreas is key organ for digestion​, Acinar cells​

​Fluid & electrolyte (HCO3-)​

• Wash out enzymes​

• Alkaline (~pH 8) to neutralise gastric acid in duodenum​

• pH optimum for intestinal digestion​

• Primary secretion from acinar cells ​

• Modified to HCO3- rich juice by duct cells​

• Around 1.5 litres per day

Pancreatic enzymes​

• Amylolytic (carbohydrate digestion)​ - Amylase​

• Proteolytic (protein digestion)​ - Trypsin, chymotrypsin, elastase​

• Lipolytic (fat digestion)​ - Lipase, phospholipase​

• Nucleolytic (nucleic acid digestion)​ - DNAse, RNAse​

​Mostly inactive precursors (zymogens) - to prevent autodigestion

enzymes in small I lumen from pancreas

trypsinogen also secreted from pancreatic duct with an anti enzyme to prevent ductal damage

This allows other enzymes to be digested

Pancreatic proteases​

• Secreted as zymogens​

• Activation by enterokinase in the intestine​

• Trypsin can auto-activate​

• so trypsin Inhibitor​ also secreted

​

• Many different proteases​

• Endo- and exopeptidases​

• Amino acid specificity​

• Protein digestion completed by intestinal peptidases​ - Brush-border membrane and cytosolic

Pancreatic HCO3- secretion​

• Acinar cell primary secretion ​- Isotonic NaCl secretion​

• Duct HCO3- secretion​

• Isotonic via apical Cl-/HCO3- exchange & CFTR Cl- channels​

​

• Cystic fibrosis​

• Absence of CFTR channels​

• Lack of fluid secretion​

• Lack of washout of enzymes​

• Damage to pancreas​

• Poor nutrition

Pancreatic secretion - control​

• Secretin​

• Duodenal S cells​

• Release stimulated by acid​

• Increases HCO3- rich secretion​

• Cholecystokinin-Pancreozymin (CCK)​

• Duodenal I cells​

• Release stimulated by fat and protein​

• Stimulates gall bladder contraction​

• Stimulates pancreatic enzyme secretion

• Neural: Vagus ​

• Stimulates both acinar cells and duct cells

S cells

I cells

bile functions

• Elimination of waste products​

• Cholesterol​

• Bile pigments (e.g. bilirubin)​

• Minerals​

• Lipophilic drugs and metabolites​

• Heavy metals​

​

• Promotion of lipid digestion and absorption

Structure of biliary tree​

Bile ​

• Hepatocytes secrete bile into canaliculi​

• Bile ducts secrete HCO3- rich fluid (like pancreas)​

• Bile enters duodenum by common bile duct​

• Between meals approximately 50% bile stored and concentrated in gall bladder

Bile ​components

• Biliary lipids​

• Bile acids (67%)​

• Phospholipids (22%)​

• lecithins​

• Cholesterol (4%)​

• Bile pigments​

• Bilirubin (0.3%) ​

• Jaundice ​

​

• Bile acids keep cholesterol in solution

Bile acids (salts)​

• Primary​

• Liver synthesis from cholesterol​

• e.g. cholic acid (cholate)

• Secondary​

• Modification by intestinal bacteria (dehydroxylation)​

• e.g. deoxycholate​

• Conjugation​

• To amino acids (glycine or taurine)​

• Increases solubility​

• e.g taurocholate ​

• Enterohepatic circulation​

• Recycling of bile acids through intestine and liver

Enterohepatic circulation of bile acids​

• Synthesis of primary bile acids in liver​

• 0.6g synthesised/ day​

• Conjugated​

• Secretion into duodenum in bile​

• 12-36g/ day secreted​

• Involved in lipid digestion/absorption​

• Reabsorption in terminal ileum​

• 0.6g lost to faeces (cholesterol excretion)​

• Recirculation through hepatic portal vein to liver​

• 3g pool in portal blood​ - very efficient

• Taken up by liver and secreted into bile​

• Can be recycled <12 times/ day

emulsification

• Bile salts coat lipids to make emulsions​

• Also phospholipids (lecithins) and cholesterol​

• Emulsification of dietary lipids increases the surface area exposed to lipases and therefore promotes digestion

allows for more efficient action of lipase

Function of gall bladder​

• Concentrates bile (< x 20)​

• Absorbs electrolytes and water​

• Isotonic​

• Na+ with bile salts​

• ~0.9l bile secreted by liver but only ~0.5l added to duodenum (mixture of dilute and concentrated bile).

Control of biliary secretion​

• Bile acid-dependent​

• Bile acid concentration in plasma​

• Ductal​

• Secretin​

• Gall bladder contraction​

• Cholecystokinin (CCK)​

• Vagal nerves (ACh)​

• integrated with pancreatic enzyme secretion

Gallstones – a failure to keep cholesterol in solution​

• Cholesterol ​

• 80%​

• Super-saturated with cholesterol​

• High ratio of cholesterol to bile salts/lecithin​

• High fat diet, females

• Or

• Pigment​

• Conjugation compromised – free bilirubin​

• Stasis – sluggish flow of bile

LOs

• List the functions of pancreatic exocrine secretions​

• Describe the mechanisms of pancreatic exocrine secretion​

• Give an account of the control of pancreatic exocrine secretions​

• Explain the functions of bile and the gall bladder​

• Give an account of the control of gall bladder contraction