Physiology of the Liver

liver and gall bladder function

1. Digestion of fat 2. Excretion of waste product

Composition of Bile

A yellow-green, alkaline solution containing bile salts, bile pigments, cholesterol, neutral fats, phospholipids, and electrolytes

Lipids

Almost 98% of dietary lipids are triglycerides (TG)

§Lipids have one thing in common - they do not mix well with water. §Lipids are hydrophobic, and thus are poorly soluble in the aqueous environment of the digestive tract. §Detergent property

Bile salt is polar and water soluble. Emulsification: In the small intestine lipids are emulsified by bile acids (i.e. formation of small droplets of lipids coated with bile acids). Bile salts function as detergents. Emulsion droplets allow access of the water-soluble lipolytic enzymes by increasing surface area. Detergent are chemical compounds that possess two characteristics: hydrophilic and hydrophobic.

•Which of the following is true regarding to bile function a)It is essentially fat insoluble b)It is essentially water insoluble c)The amount lost in the stool each day represents daily loss of cholesterol d)Bile acids are more effective detergents than bile salts e)The majority of the bile are absorbed by passive diffusion ●

C (rest are false)

Internal Structure of the Liver lobular structure

Portal triad = portal area Kupffer cells Hepatocytes

The liver is responsible for removing the small numbers of bacteria that enter the portal circulation from the intestines. Which cell type fulfills this function? A. Sinusoidal epithelial cells B. Hepatocytes C. Kupffer cells D. Stellate cells E. Dust cells

Rationale: a. Incorrect. A liver sinusoid (Sinusoidal epithelial cells) is a type of sinusoidal blood vessel (with fenestrated, discontinuous endothelium) that serves as a location for the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein b. Incorrect. A hepatocyte is a cell of the main parenchymal tissue of the liver c. Correct. Kupffer cells are liver macrophages which kills bacteria d. Incorrect. Hepatic stellate cell is the major cell type involved in liver fibrosis, which is the formation of scar tissue in response to liver damage. e. Incorrect. Dust cells (alveolar macrophages) is a type of macrophage found in the pulmonary alveolus, near the pneumocytes

Bile micelles initially form in the: A. Hepatocyte cytoplasm B. Hepatic cell membrane C. Bile canaliculi D. Large bile ducts E. Gallbladder

Rationale: a. Incorrect. Cytoplasmic formation could damage hepatocytes. b. Incorrect. Bile acids and salts are transported through the membrane by carriers. c. Correct. Bile micelles form in canaliculi because the bile components reach a critical concentration in the canaliculi. d. Incorrect. Micelles form in canaliculi. e. Incorrect. Micelles form in canaliculi.

A patient presented with history of diarrhea with steatorrhea. Which of the following best explains the cause of excessive fat in the stools? A. Delayed gastric emptying B. Decrease secretion of amylase C. Decrease bilirubin secretion from liver D. Decreased bile salt pool E. Decreased pepsinogen secretion

Rationale: a. Incorrect. Delayed gastric emptying doesn't cause steatorrhea b. Incorrect. Decrease secretion of amylase doesn't cause steatorrhea as amylase is CHO digesting enzyme c. Decrease bilirubin secretion doesn't cause steatorrhea d. Correct. Decreased bile salt pool can results in an increased delivery of fats into the colon which in turn inhibits fat absorption and promotes water secretion e. Incorrect. Decreased pepsinogen secretion doesn't cause steatorrhea as this is protein digesting enzyme

The carrier or channel that drives reabsorption of water in the gallbladder and causes the bile to be concentrated is: A. Cystic fibrosis transmembrane regulator B. Cl:HCO3 exchanger C. Na+, K+-ATPase D. Na:K:2Cl carrier E. Na:HCO3 carrier Rationale:

The carrier or channel that drives reabsorption of water in the gallbladder and causes the bile to be concentrated is: A. Cystic fibrosis transmembrane regulator B. Cl:HCO3 exchanger C. Na+, K+-ATPase D. Na:K:2Cl carrier E. Na:HCO3 carrier Rationale: a. Incorrect. Regulator is not involved in gallbladder water reabsorption. b. Incorrect. Cl:HCO3 exchanger is not involved in gallbladder water reabsorption. c. Correct. Sodium pump action creates an osmotic difference that causes water reabsorption in the gallbladder. d. Incorrect. Na:K:2Cl carrier is not involved in gallbladder water reabsorption. e. Incorrect. Na:HCO3 carrier is not involved in gallbladder water reabsorption.

Bile Salt Deficiency: Cholelithiasis

The movement of cholesterol from the liver into the bile must be accompanied by the simultaneous secretion of phospholipid and bile salts. If this dual process is disrupted and more cholesterol enters the bile than can be solubilized by the bile salts, the cholesterol may precipitate in the gallbladder, initiating the occurrence of cholesterol gallstone disease—cholelithiasis

Bile salts are transported out of hepatocytes by: A. Active transport B. Secondary active transport C. Facilitated diffusion D. Diffusion through lipid bilayer E. Exocytosis

a

The correct statement about the function of the gall bladder is: A. Concentrates bile by removal of water B. Adds bile salts to bile C. Dilutes and neutralizes bile by adding bicarbonate and water D. Removes cholesterol from bile E. Stores bile but does not modify it in any way

a

What structure in the liver permits chylomicron remnants to access the basolateral membranes of hepatocytes? A. Canaliculi B. Sinusoidal fenestrae C. Kupffer cells D. Bile ducts E. Tight junctions

a. Incorrect. Portal blood brings nutrients towards sinusoidal fenestrae to get them enter into hepatocytes. Bile is secreted into canaliculi b. Correct. Sinusoi Portal blood brings nutrients towards sinusoidal fenestrae to get them enter into hepatocytes. c. Incorrect. Kupffer cells are macrophages in liver. d. Incorrect. Bile ducts drain bile into canaliculi. e. Incorrect. Portal blood brings nutrients towards sinusoidal fenestrae to get them enter into hepatocytes. Basolateral membrane of hepatocytes have leaky channels.

Bile acid binding proteins are found in: A. Hepatocyte cell membranes B. Bile C. Hepatocyte cytoplasm D. Succus entericus E. Small intestine absorptive cell membranes

c

Opening of the sphincter of Oddi is regulated by: A. Gastrin B. Secretin C. Cholecystokinin D. Histamine E. Molitin

c

The relative solubilities of bile steroids in body fluids are: A. Cholesterol >bile acids >bile salts B. Bile acids >cholesterol >bile salts C. Cholesterol = bile acids >bile salts D. Bile salts >bile acids >cholesterol E. Bile acids >bile salts = cholesterol

d

Glycine or taurine is a component of: A. Cholesterol B. Biliverdin C. Bile acids D. Phospholipids E. Bile salts

e

enterohepatic circulation §Recycles bile salts between the blank and blank §blank% of Bile reabsorbed in the terminal blank §They are actively transported from the intestinal mucosal cells into the portal blood.

recycling mechanism that conserves bile salts §Recycles bile salts between the small intestine and the liver §95% of Bile reabsorbed in the terminal ileum. §They are actively transported from the intestinal mucosal cells into the portal blood.

Micelles small transport carriers in the intestine that enable fatty acids and other compounds to be blank •Allow lipids access to blank •Provide a large surface area for the action of pancreatic blank •Micelles are about 200 times smaller than emulsion droplets (4-7nm versus 1µm for emulsion droplets). •Micelles contain fblank and blank

small transport carriers in the intestine that enable fatty acids and other compounds to be absorbed •Allow lipids access to enterocytes •Provide a large surface area for the action of pancreatic lipase •Micelles are about 200 times smaller than emulsion droplets (4-7nm versus 1µm for emulsion droplets). •Micelles contain fat soluble vitamins and cholesterol.

Bile §Bile is composed of §Bile is yellow-green fluid, produced in the blankr, stored in the blank, and secreted into the blank.

§Bile is composed of bile salts (bile acids conjugated to glycine or taurine), phospholipids, cholesterol, bilirubin , water and ions. §Bile is yellow-green fluid, produced in the liver, stored in the gallbladder, and secreted into the duodenum.

§Bile salts in the small intestine are absorbed via:

§Bile salts in the small intestine are absorbed via: 1.Active Carrier-mediated transmembrane process - Sodium-Bile Salt Cotransporter - Active Transport 2.Passive Diffusion

Functions of Bile immunoglobin

§Digestion and absorption of lipids and fat-soluble vitamins. Emulsification: when exposed to water, bile salts forms micelles §Cholesterol excretion §Antimicrobial activity (via membrane disruption) §Immunoglobulin A inhibit bacterial growth in the small intestine §Creates optimum pH for pancreatic enzymes to work in duodenum §DOES NOT contain enzymes Fat soluble vitamins : A, D, E and K? Bile breaks down large lumps of fat into smaller lumps and help to neutralize stomach acids

Action of intestinal flora on bile acids primary to secondary bile acid §Intestinal bacteria can convert some of the primary bile acids into secondary bile acids by removing a blank group, producing deoxycholic acid from cholic acid and lithocholic acid from chenodeoxycholic acid.

§Intestinal bacteria can convert some of the primary bile acids into secondary bile acids by removing a hydroxyl group, producing deoxycholic acid from cholic acid and lithocholic acid from chenodeoxycholic acid.

Functions of the Liver (in terms of bile)

§Production of bile, which: §Helps carry away waste. Cholesterol excretion (only route) §Detoxification ( drugs, harmful substances) §Conversion of harmful ammonia to urea §Removes a number of substance from the plasma, such as bilirubin (heme, product of hemoglobin degradation) §Synthesis of fatty acids, cholesterol and many of the plasma proteins §Break down fats in the small intestine during digestion §Store glucose as glycogen, iron, vitamin B12 §Resisting infections by producing immune factors

Gallbladder Function §Store blank. §Contains smooth blank §Concentrate the bile by removal of water. Reabsorption of water can increase the concentration of bile salt as much as twenty times. §blank and blank are actively absorbed by the gallbladder epithelium

§Store bile. §Contains smooth muscle §Concentrate the bile by removal of water. Reabsorption of water can increase the concentration of bile salt as much as twenty times. §Chloride and bicarbonate are actively absorbed by the gallbladder epithelium

Lipid Digestion & Absorption •Free fatty acids and monoglycerides reformed into blanks inside the enterocytes. •CHYLOMICRONS formation •Chylomicrons pass through the thoracic duct before passing through the liver

•Free fatty acids and monoglycerides reformed into triglycerides inside the enterocytes. •CHYLOMICRONS formation •Chylomicrons pass through the thoracic duct before passing through the liver Delivery of triglycerides digestion products from micelles - Diffusion across apical membrane - Synthesis of triglycerides. Because chylomicrons are too large to enter the capillaries, they are transferred to lymphatic vessels and are added to the bloodstream via the thoracic duct.

Bile Synthesis •Hepatocytes synthesize bile from cholesterol by adding blankl groups •Primary bile acids: blank and blank Acid •Bile acids get conjugated in the liver with blank and blanke: BILE SALT •Bile salts are more effective blank than bile acids •Bile salts have greater solubility in blankr than bile acids (salt vs acid)

•Hepatocytes synthesize bile from cholesterol by adding hydroxyl groups •Primary bile acids: Cholic and Chenodeoxycholic Acid •Bile acids get conjugated in the liver with taurine and glycine: BILE SALT •Bile salts are more effective detergents than bile acids •Bile salts have greater solubility in water than bile acids