Histology of the Liver

Liver Overview

• The liver is the 2nd largest organ in the body and the largest gland.
• It receives blood from the portal vein and hepatic artery, and drains into the IVC.

Functions of the Liver

• Detoxification of metabolic waste products (e.g., de-amination of amino acids to produce urea)
• Destruction of spent RBCs
• Synthesis and secretion of bile
• Synthesis of plasma proteins (e.g., albumin, clotting factors)
• Synthesis of plasma lipoproteins
• Metabolic functions (e.g., glycogen synthesis, gluconeogenesis, storage of glycogen, vitamins, and lipids)
• Detoxification of various drugs and toxins (e.g., alcohol)

Stroma of the Liver

• Connective tissue (Glisson's capsule) surrounds the liver
• Thick at the hilum, with blood vessels and ducts surrounded by connective tissue
• Reticular fibers support liver cells and sinusoids

Hepatic Lobule

• Hepatocytes are epithelial cells
• Lobules are the structural unit of the liver (0.7 x 2 mm)
• Each lobule has a portal area (portal triad), central vein, and 3-6 portal spaces
• Hepatocytes form interconnecting plates that branch and anastomose

Portal Triad

• A branch of the portal vein, hepatic artery, bile duct, lymphatics, and nerves
• Portal vein is the largest structure, thin-walled, and lined with endothelium
• Hepatic artery is the smallest structure
• Bile duct is lined with cuboidal epithelium
• Lymphatics are delicate and collapsed
• Nerves are present

Hepatic Sinusoids

• Dilated veins with incomplete basement membrane
• Supported by reticular fibers
• Contain endothelial cells (fenestrated, without diaphragm), Kupffer cells (macrophages), and stellate cells

Perisinusoidal Space (of Disse)

• A subendothelial space between hepatocytes and sinusoids
• Microvilli of hepatocytes project into the space
• Fat-storing (Ito) cells that store vitamin A are present
• The space is continuous with sinusoids and drains into lymphatics of the portal triad

Medical Applications

• Ito cells acquire myofibroblast features in chronic liver disease
• Alcoholic liver disease can lead to fibrosis
• Vitamin A-rich lipid inclusions, uptake, storage, and release of retinoids, and synthesis and secretion of ECM proteins and proteoglycans

Blood Supply

• Portal vein (70%) and hepatic artery (30%)
• Direction of blood flow is from the periphery to the center of the lobule
• Difference in properties and functions of peripheral and centrolobular hepatocytes

Hepatocytes

• Polyhedral cells (20-30µm), eosinophilic, with a large nucleus and binucleate
• Bile canaliculi are present, and gap junctions exist between hepatocytes
• Surfaces relate to perisinusoidal space, adjacent hepatocyte, and bile canaliculi

Fine Structure of Hepatocytes

• Rough endoplasmic reticulum (protein synthesis)
• Smooth endoplasmic reticulum (oxidation, methylation, and synthesis of bile acids)
• Golgi apparatus (formation of lysosomes, secretion of proteins, glycoproteins, and lipoproteins)
• Lysosomes (turnover and degradation of organelles)
• Mitochondria (oxidative phosphorylation)
• Peroxisomes (β-oxidation of fatty acids, oxidation of hydrogen peroxide)

Bile Canaliculi

• 1-2µm in diameter, limited by the plasma membrane of hepatocytes
• Tight junctions are present, and canaliculi empty into bile ductules lined by cuboidal cells (cholangiocytes)
• Bile ducts are present in portal spaces, and the direction of bile flow is opposite to that of blood flow

Medical Applications

• Disorders of peroxisome function can lead to inherited diseases (e.g., adrenoleukodystrophy)
• Jaundice can occur when bilirubin or bilirubin glucuronide is not excreted properly
• Neonatal hyperbilirubinemia can be treated with blue light exposure
• Gallstone formation can cause obstruction of bile flow and jaundice