Liver and Gallbladder Anatomy

• The liver and gallbladder are essential organs in the digestive system

Functional Anatomy of the Liver and Biliary System

• Liver functions as both a secretory and excretory organ
• Largest gland in the human body, weighing about 1.5 kg
• Located on the upper right side of the abdominal cavity, just below the diaphragm

Liver

• Composed of hepatic lobes, which consist of multiple hepatic lobules

Hepatic Lobules

• Liver's structural and functional units with 50,000 to 100,000 lobules
• Exhibiting a honeycomb-like structure made of liver cells known as hepatocytes

Hepatocytes and Hepatic Plates

• Hepatocytes arrange in columns to create hepatic plates, each formed by two columns of cells with bile canaliculus in between
• Sinusoid, a blood space, exists between neighboring plates, lined by endothelial cells and Kupffer cells (special macrophages)

Portal Triads

• Portal triads surround each lobule and contain three vessels
• A branch of the hepatic artery
• A branch of the portal vein
• A tributary of the bile duct
• Hepatic artery and portal vein branches flow into the sinusoid, which then opens into the central vein that empties into the hepatic vein

Biliary System

• Consists of the gallbladder and extrahepatic bile ducts
• Right and left hepatic ducts merge to form the common hepatic duct
• Common hepatic duct joins the cystic duct from the gallbladder forming the common bile duct
• The common bile duct merges with the pancreatic duct forming the hepatopancreatic duct (ampulla of Vater), which empties into the duodenum
• Sphincter of Oddi, located at the lower part of the common bile duct controls bile flow into the intestine

Blood Supply to Liver

• Liver receives ~1,500 mL/minute of blood from the hepatic artery and portal vein

Hepatic Artery

• Originates directly from the aorta and supplies the liver with oxygenated blood
• After entering the liver, the hepatic artery divides into many branches and enters a portal triad

Portal Vein

• Formed by the superior mesenteric and splenic veins
• Carries deoxygenated blood from the stomach, intestine, spleen, and pancreas
• Blood is rich in monosaccharides, amino acids, bile salts, bilirubin, urobilinogen, and GI hormones, but has lower oxygen content
• Blood flow from the intestine to the liver via the portal vein is known as enterohepatic circulation

Hepatic Vein

• Substances synthesized by hepatic cells, waste products, and carbon dioxide are discharged into sinusoids
• Sinusoids drain into the central vein of the lobule
• Central veins unite to form bigger hepatic veins, which empty into the inferior vena cava

Properties and Composition of Bile

• Daily volume secreted is 800 to 1,200 mL
• Alkaline with a pH of 8 to 8.6
• Specific gravity ranges from 1.010 to 1.011
• Color: golden yellow or green

Composition of Bile

• Consists of 97.6% water and 2.4% solids, including organic and inorganic substances

Secretion of Bile

• Hepatocytes secrete bile containing bile acids, bile pigments, cholesterol, lecithin, and fatty acids
• Bile is released into canaliculi, then passes through small ducts, hepatic ducts, and the common hepatic duct
• From the common hepatic duct, bile is diverted into either the intestine or gallbladder
• Sodium, bicarbonate, and water is added in the ducts; these substances are secreted by the epithelial cells of the ducts, increasing the total quantity of bile

Storage of Bile

• Most of the bile enters the gallbladder for storage, and it is released into the intestine when needed

Changes in Bile During Storage

• Volume decreases due to absorption of water and electrolytes (except calcium and potassium)
• Concentrations of bile salts, bile pigments, cholesterol, fatty acids, and lecithin increase
• pH decreases slightly
• Specific gravity increases
• Mucin is added

Bile Salts

• Sodium and potassium salts of bile acids, conjugated with glycine or taurine

Formation of Bile Salts

• Bile salts form from bile acids, primary being cholic acid and chenodeoxycholic acid
• Primary bile acids are converted by bacteria into secondary bile acids
  • Cholic acid converted to deoxycholic acid
  • Chenodeoxycholic acid converted to lithocholic acid
• Secondary bile acids are transported back to the liver via enterohepatic circulation and conjugated with glycine or taurine, creating glycocholic and taurocholic acids which combine with sodium or potassium ions

Enterohepatic Circulation of Bile Salts

• Substances transport from the small intestine to the liver via the portal vein
• 90-95% of bile salts are transported to the liver
• Remaining 5-10% enter the large intestine where they are converted into deoxycholate and lithocholate, then excreted in feces

Functions of Bile Salts

• Digestion and absorption of fats in the intestine
• Emulsification
  • Fat globules are broken down into minute droplets forming an emulsion
  • Lipolytic enzymes cannot digest fats directly due to their insolubility in water
  • Bile salts reduce surface tension which allows fats to be easily digested
• Absorption of Fats
  • Bile salts combine with digested fats, forming micelles, that are easily absorbed
• Choleretic Action
  • Stimulate bile secretion from the liver
• Cholagogue Action
  • Cause contraction of the gallbladder
• Laxative Action
  • Stimulate peristaltic movements of the intestine
• Prevention of Gallstone Formation
  • Keep cholesterol and lecithin in solution

Bile Pigments

• Excretory products found in bile; bilirubin is the major pigment

Fate of Conjugated Bilirubin

• Stages of excretion
  • 50% of conjugated bilirubin is converted to urobilinogen by intestinal bacteria (deconjugated to free bilirubin then reduced to urobilinogen)
  • Remaining 50% is absorbed into blood and re-excreted through bile (enterohepatic circulation)
  • Most urobilinogen from the intestine enters the liver and is re-excreted through bile
  • About 5% of urobilinogen is excreted by the kidney into urine
  • Some urobilinogen is excreted in feces as stercobilinogen

Normal Plasma Levels of Bilirubin

• Normal bilirubin content is 0.5 to 1.5 mg/dL
• Levels exceeding 1 mg/dL is hyperbilirubinemia and levels exceeding 2 mg/dL indicates jaundice

Functions of Bile

• Most functions are due to bile salts
• Digestive - See functions of bile salts
• Absorptive - See functions of bile salts
• Excretory
  • Bile pigments are major excretory component
  • Heavy metals such as copper and iron
  • Some bacteria, like typhoid
  • Some toxins
  • Cholesterol
  • Lecithin
  • Alkaline phosphatase
• Laxative - Bile salts act as laxatives
• Antiseptic - Inhibits certain bacteria growth
• Choleretic - Bile salts have choleretic action
• Maintenance of pH in GI Tract
  • Alkaline, neutralizes acidic chyme to help digestive enzymes action
• Prevention of Gallstone Formation
  • Refer function of bile salts
• Lubrication - Mucin acts as a lubricant
• Cholagogue - Bile as cholagogues

Functions of Liver

• Largest gland and vital organ of the body
• Metabolic
  • Site for metabolic reactions like carbs, proteins, fats, and vitamins
• Storage
  • Stores glycogen, amino acids, iron, folic acid, vitamins A, B12, and D
• Synthetic
  • Produces glucose
  • Synthesizes plasma proteins, clotting factors, complement factors, hormone-binding proteins, steroids, somatomedin, and heparin
• Secretion of Bile
  • Bile contains bile salts, bile pigments, cholesterol, fatty acids, and lecithin. Bile salts digest and absorb fats
• Excretory
  • Excretes cholesterol, bile pigments, heavy metals, toxins, bacteria, and viruses through bile
• Heat Production
  • Produces large amounts of heat
• Hemopoietic
  • Produces blood cells in the fetus and stores vitamin B12 and iron

Liver Functions Continued

• Production of thrombopoietin to promote thrombocytes
• Hemolytic - Senile RBCs (120 days lifespan) are destroyed by reticuloendothelial cells (Kupffer cells)
• Inactivation of Hormones and Drugs
  • Catabolizes hormones (growth, parathormone, cortisol, insulin, glucagon, estrogen)
  • Inactivates drugs (fat-soluble are converted to water-soluble substances and excreted through bile or urine)
• Defensive and Detoxification
  • Reticuloendothelial cells (Kupffer) in liver defend the body
  • Swallows and digests, produces substances activitating immune system/removes harmful substances

Gallbladder

• Stores bile secreted from the liver
• Gallbladder capacity is ~50 mL
• Not essential for life, can be removed without major disadvantage

Functions of Gallbladder

• Storage - Stores bile until required
• Concentration - Concentrates bile by reabsorbing water and electrolytes, bile increases 5-10 times
• Alteration of pH - pH decreases and is less alkaline in gallbladder
• Secretion of Mucin - Secretes mucin, which acts as a lubricant in the intestine
• Maintenance of Pressure - Maintains pressure in the biliary system for bile release

Filling and Emptying of Gallbladder

• Sphincter of Oddi is usually closed so bile from liver moves to gallbladder
• When food is taken, the gallbladder contracts, pressure increases which sends more bile into inestine. Contraction is influenced by neural and hormonal factors

Regulation of Bile Secretion

• Continuous process, decreasing during fasting
  • Increases post meals, lasting three hours
• Influenced by neural and hormonal factors

Neural Factor

• Parasympathetic nerve (vagus) stimulates contraction of the gallbladder by releasing acetylcholine

Hormonal Factor

• Fatty chyme in the intestine stimulates secretion of cholecystokinin/contraction of gallbladder

Chemical Factors Influencing Bile Secretion

• Choleretics
  • Increase bile secretion from the liver (i.e. acetylcholine and bile salts)
• Cholagogues
  • Increase the release of bile into the intestine by contracting the gallbladder
• Hydrocholeretic agents
  • These cause the secretion of bile with a large amount of water

Applied Physiology

• Jaundice (Icterus)
  • Yellow coloration of skin due to increased bilirubin
  • Normal level is 0.5 to 1..5mg/dL
  • Exceeds 2 mg/Dl to be considered jaundice

Types of Jaundice

• Prehepatic
  • Hemolytic jaundice (excess destruction RBC resulting in increased bilirubin)
• Hepatic
  • Hepatocellular or cholestatic jaundice is damage to hepatic cells
• Posthepatic/Obstructive
  • Bile is unable to be excreted in SI, increasing bile salts and pigments entering circulation

Hepatitis

• Liver damaged caused by agents, which is characterized by swelling and inadequate functioning
• This can be acute or chronic, leading to liver failure

Cirrhosis of Liver

• Inflammation and damage to parenchyma, results in degeneration

Gallstones

• Solid crystal deposit consisting of cholesterol, calcium ions, and bile pigments
• Cholelithiasis is gallstones In the gallbladder
• Choledocholithiasis is gallstones in the bile ducts

Formation of Gallstones

• Excess cholesterol precipitates
• Small quantity begins to precipitate
• Growing crystals attach to bile pigments and calcium forming gallstones

Causes For GallStone Formation

• Reduction in bile salts
• Excess Cholesterol
• Disturbed cholesterol metabolism
• Excess of Calcium
• Altered Absorbtive function of epithelium
• Obstructed Bile Flow