Liver Functions, Bile Acid Synthesis and Gallstones

• The material provides an overview of the transport and metabolic functions of the liver, bile acid synthesis, and gallstone formation

Functional Anatomy

• Key components include hepatocytes, cholangiocytes, endothelial cells, and Kupffer cells
• The liver filters blood from the GIT, receiving blood via portal vein
• The structural unit of the liver is the Acinus
• The branches of the hepatic vein, hepatic artery, and bile ducts are where the Hepatic Triad can be located
• Periportal/Zone 1 is closest to the hepatic triad, having the greatest oxygen and nutrient supply and is more active in detoxification
• Pericentral/Zone 3 lies closest to branches of the central vein, is more sensitive to ischemia, and is most active in bile acid synthesis

Biliary System

• Canaliculus are formed by apical membranes of adjacent hepatocytes and drain bile from the liber
• The biliary ductules are lined by columnar epithelial cells
• The biliary ductules drain into larger bile ducts which then form the common hepatic duct

Metabolic Functions of the Liver

• The liver Stores glucose as glycogen when glucose levels are high and releases it when needed
• Lipids are metabolized through fatty acid oxidation which convert products to lipids and produce lipoproteins, cholesterol, and phospholipids
• It converts a portion of synthesized cholesterol to bile acids
• Nonessential amino acids are synthesized, interconverted, and deaminated so the products can enter biosynthetic pathways for carbohydrate synthesis
• Almost all plasma proteins are synthesized in the liver
• Ammonia generated from protein catabolism is converted to urea for renal excretion

Liver and Detoxification

• The liver limits entry of toxic substances into the bloodstream
• It extracts potential toxic metabolic products and converts them into chemical forms that can be excreted

Substance Removal and Detoxification

• Kupffer cells are phagocytic and remove particulate material from portal blood, bacteria can also enter through the colon
• Endogenous and exogenous toxins undergo biochemical modification into water-soluble products less susceptible to reuptake in the intestine
• Phase I reactions: oxidation, hydroxylation, and other reactions by cytochrome P450 enzyme
• Phase II reactions: conjugation promotes excretion
• Liver disease can result in apparent overactivity of the relevant hormone system and affect drug metabolism

Bile

• The liver produces bile and the gallbladder stores it
• Bile is composed of bile salts, bile pigments, and other substances dissolved in an alkaline electrolyte solution
• Bile aids in digestion and absorption of lipids
• Bile also facilitates the excretion of waste products like bilirubin and excess cholesterol

Bile Composition

• Water comprises 97.0%
• Bile acids account for 0.7%
• Bile pigments contribute 0.2%
• Cholesterol makes up 0.06%
• Bile pools daily synthesis equals ~10% of the fraction lost in stool

Enterohepatic Circulation of Bile Acids

• Bile acids recirculate between the liver, gallbladder, and small intestine
• About 94% of bile salts are reabsorbed into the blood from the small intestine
• Problems arise if there is damage or a tumor of the small intestine especially the ileum
• Small quantities of bile salts lost are replaced by new amounts from the liver synthesis

Bilirubin Formation and Excretion

• Bilirubin is a metabolite of heme
• Heme oxygenase liberates iron from the heme molecule and produces biliverdin

Jaundice

• This occurs accumulation in the circulation caused by liver disease
• Skin and membranes turn yellow as a result of high unconjugated bilirubin

Bile Acid Synthesis

• Hepatocytes produce bile acids as end products of cholesterol metabolism
• Bile acid secretion occurs in hepatocytes and canaliculi

Bile Constituents

• Mixed micelles are composed of bile acids, cholesterol, and phosphatidylcholine
• This is osmotically active, and the junctions that link cells are relatively leaky water is drawn into the canal lumen

Bile Modification in Ductules

• Cholangiocytes, which line biliary ductules, modify the composition of bile
• Useful solutes are reclaimed for activity transport

Role of the Gallbladder

• The gallbladder stores bile and removes the sodium

Biliary Secretion

• Cholecystokinin is critical mediator

Gallstone Formation

• There are two formation types
• Calcium bilirubinate comes from hematologic dyscrasia from accumulation of Heme.
• Cholesterol as a the most common from fatty food which overwhelm the production of bile