NS 3310 1st Edition Lecture 5Outline of Past LectureI. Cells in glands in gastric pitsII. Gastric juiceIII. Regulation of gastric secretionIV. Small IntestineOutline of Current LectureI. Basics of LiverII. Bile Synthesis in Liver III. Enterohepatic Circulation of BileIV. Clinical RelevanceV. PancreasVI. Absorptive ProcessesCurrent LectureI. Basics of Liver- The liver receives nutrient-rich blood from the hepatic portal system -After food enters the enterocyte, it goes into a vein called the hepatic portal vein-This vein goes to the liver delivering nutrientsThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- The liver is composed of lobes made of lobules, which are a functional unit that is made up of plates or sheets of hepatocytes-Hepatocytes are arranged in rows that radiate out from the central vein; they are bathed in blood- There are some important structures to know -Portal vein: this is where the nutrients come from-Hepatic artery: allows hepatocytes to quickly take up nutrients and metabolize them-Bile duct: branches off into bile canaliculi and collects bile from bile acids, which come from hepatocytes-Central vein: blood and nutrients from intestine is moving from portal vein to this central vein- The two main cells that are present are sinusoid and kupfferII. Bile Synthesis in Liver- Bile is produced and secreted by hepatocytes into a special duct called bile canaliculus- Bile synthesis: -Formation of bile acids cholic acid and chenodeoxycholic acid from cholesterol (cholesterol is the precursor for bile acids)-Rate-limiting enzyme is cholesterol 7a-hydroxylase and it is negatively regulated by bile acids and FXR (a member of the nuclear receptor superfamily): catalyzes conversion of cholesterol to bile acid -Then conjugated with glycine and taurine - Bile is concentrated, stored and secreted by the gallbladder -Secreted through bile duct and sphincter of Oddi into the lumen of the duodenum- Due to its high pH, most conjugated bile acids are present as bile salts with sodium - The constituents of bile are: bile acids/salts, cholesterol, phospholipids, and bile pigments dissolved in alkaline solution- Function of bile: to act as detergents to emulsify lipids (break down large fat globules into small droplets which allow enterocytes to absorb) and to form small spherical complexes called micellesIII. Enterohepatic Circulation of Bile- Over 90% of bile acids and salts that are secreted into the duodenum are reabsorbed by active transport in the ileum- 50% of cholesterol contained within the bile is reabsorbed by the jejunum and used in forming chylomicrons - Process of enterohepatic circulation-Bile is made in the liver and is transported to the gallbladder and stored-When the gallbladder contracts, bile is released into the cystic duct. The cystic duct joins the common bile duct-Bile aids in lipid digestion by enabling large lipid globules to disperse in the watery environment of the small intestine -After aiding in lipid digestion, the bile constituents are reabsorbed from the ileum and returned to the liver by the hepatic portal vein-The liver uses these constituents to resynthesize bile which is then stored in the gallbladderIV. Clinical Relevance- Bile acid sequestrants-Drug therapy and functional foods to treat high blood cholesterol (hypercholesterolemia) -Medications: Questran-Functional food: add plant stanols and sterols to food to target enterohepatic circulation. Plant stanols and sterols can bind to cholesterol and bile acids/bile salts reducing reabsorption/circulation. Reducing circulation is so important because if less circulation, the body has to make more and since bile acids are made of cholesterol, this lowers cholesterolV. Pancreas- Pancreas has two different parts: endocrine and exocrine-Endocrine part secretes hormones into blood circulation, specifically insulin (secreted by beta cells) and glucagon (secreted by alpha cells)-Exocrine part has acinar cells that form a circular pattern that are connected to a duct; this duct connects to a bigger duct called the pancreatic duct. There are duct cells along the duct and they secrete bicarbonate solution for neutralizing acidic chyme- Function of exocrine pancreas:-Digestive enzymes produced by acinar exocrine cells-Pancreatic juice contains bicarbonate, electrolytes, and pancreatic digestive enzymes-Regulation of pancreatic secretionsVI. Absorptive Processes- Digestion: breaking nutrients down occurs in lumen and at brush border- Most digestion and absorption occur in small intestine; unabsorbed materials continue to colon- The colon or large intestine contracts to mix materials; intestinal bacterial populations exist here- Absorption may be by diffusion, facilitated diffusion, active transport or pinocytosis/endocytosis - Mechanism of absorption depends on solubility, concentration or electrical gradient and size of