Histological Structure of Liver, Pancreas, Gall Bladder

Organs Associated with the Digestive Tract

• Major Salivary Glands
• Pancreas
• Liver
• Gallbladder
• Functions:
  • Facilitate movement & digestion within the gastrointestinal tract
  • Secrete digestive enzymes, bile, and immune components

Salivary Glands

• Main Functions:
  • Moisten and lubricate food & oral mucosa
  • Initiate carbohydrate and lipid digestion (amylase & lipase)
  • Secrete innate immune factors (lysozyme, lactoferrin)

Liver & Gallbladder

Liver:

• Exocrine secretion: bile for fat digestion
• Metabolism of carbohydrates & proteins
• Detoxifies substances & drugs
• Synthesizes plasma proteins and coagulation factors

Gallbladder:

• Stores and concentrates bile
• Releases bile into the duodenum

Pancreas Overview

• Mixed exocrine–endocrine gland
• Retroperitoneal, elongated organ
• Divided into head, body, and tail
• Thin connective tissue capsule with septa separating lobules

Pancreatic Structure

• Exocrine Portion: Serous acini produce digestive enzymes
• Endocrine Portion: Islets of Langerhans produce hormones
• Rich capillary network
• Sparse stroma, delicate reticular fiber sheath

Pancreatic Cancer

• Usually carcinoma of duct cells
• Most frequent in pancreatic head
• Often asymptomatic until advanced
• Early detection is difficult, prognosis poor
• Facilitated by sparse connective tissue around ducts

Exocrine Pancreas - Histology

• Serous acini: Protein-secreting pyramidal cells
• Central lumen, no myoepithelial cells
• Drained by intercalated ducts lined by centroacinar cells (unique)
• Intercalated → Intralobular → Interlobular → Main pancreatic duct

Pancreas Low-Power View

• Includes several islets (I) surrounded by many smaller serous acini (A).
• The larger intralobular ducts (D) are lined by simple columnar epithelium.
• The ducts and blood vessels (V) are embedded in connective tissue, which also provides a thin capsule to the entire gland and thin septa separating the lobules of secretory acini.

Pancreatic Juice & Digestive Enzymes

• Secretes 1.5 L/day of alkaline pancreatic juice
• HCO₃ ⁻ neutralizes gastric acid in duodenum
• Enzymes:
  • Proteases (as zymogens: trypsinogen, chymotrypsinogen, etc.)
  • α-Amylase
  • Lipases
  • Nucleases (DNAase, RNAase)

Enzyme Activation & Protection Mechanisms

• Protease activation restricted to duodenum
• Trypsin inhibitor in zymogen granules
• High pH in ducts (HCO₃ ⁻) keeps enzymes inactive

Centroacinar and Intercalated Duct Cells

• Under the influence of secretin, the centroacinar and intercalated duct cells secrete a copious HCO3^−-rich fluid that hydrates, flushes, and alkalinizes the enzymatic secretion of the acini

Pancreatic Acinar Cell

• TEM of a pancreatic acinar cell shows its pyramidal shape and the round, basal nucleus (N) surrounded by cytoplasm packed with cisternae of rough ER (RER).
• The Golgi apparatus (G) is situated at the apical side of the nucleus and is associated with condensing vacuoles (C) and numerous secretory granules (S) with zymogen.
• The small lumen (L) of the acinus contains proteins recently released from the cell by exocytosis.
• Exocytosis of digestive enzymes from secretory granules is promoted by CCK, released by enteroendocrine cells of the duodenum when food enters that region from the stomach.

Pancreatitis

Acute Pancreatitis:

• Proenzymes activated within pancreas → autodigestion
• Causes: infection, gallstones, alcohol, drugs, trauma

Chronic Pancreatitis:

• Progressive fibrosis
• Loss of pancreatic function

Regulation of Exocrine Secretion

By Enteroendocrine Hormones:

• Cholecystokinin (CCK): Stimulates acinar enzyme secretion
• Secretin: Stimulates HCO₃ ⁻ and water secretion from ducts

By Nervous Control:

• Parasympathetic (autonomic) nerve fibers stimulate both acinar & ductal cells

The Liver

• Is the largest internal organ (~1.5 kg, ~2% body weight)
• Located in the right upper quadrant beneath the diaphragm
• Supported by ligaments; divided into left and right lobes
• Covered by Glisson’s capsule and visceral peritoneum

Blood & Bile Supply

• Dual blood supply:
  • 75% via nutrient-rich portal vein
  • 25% via oxygen-rich hepatic artery
• Bile produced by hepatocytes → bile canaliculi → bile ducts → gallbladder or duodenum

Hepatocyte Functions

• Exocrine: bile production
• Endocrine: plasma proteins (albumin, fibrinogen, transferrin)
• Gluconeogenesis
• Detoxification of drugs & toxins
• Amino acid deamination → urea
• Storage: glycogen, triglycerides, vitamins, iron
• Phagocytosis: aged RBCs by Kupffer cells

Hepatic Lobule Diagram

• (a) Diagram showing a small central vein in the center of a hepatic lobule and several sets of blood vessels at its periphery. The peripheral vessels are grouped in connective tissue of the portal tracts and include a branch of the portal vein, a branch of the hepatic artery, and a branch of the bile duct (the portal triad).
• (b) This diagram indicates the flow of arterial (red) and venous (blue) blood from two vessels in the portal tract, and how this blood mixes in the hepatic sinusoids. Both blood vessels branch and join sinusoids which run between plates of hepatocytes and drain into the central vein. Flow of bile to a bile ductule is also shown here (green)
• (c) Micrograph of a lobule shows the central vein (C), plates of hepatocytes (H), and in an adjacent portal area a small lymphatic (L) and components of the portal triad: a portal venule (PV), hepatic arteriole (HA), and bile ductule (B).

Hepatic Lobule Structure

• Classic lobule: hexagonal unit with central vein
• Portal triads at periphery:
  • Portal vein branch
  • Hepatic artery branch
  • Bile ductule
• Blood flows from portal triads → sinusoids → central vein

Hepatic Lobules

• Cut transversely, hepatic lobules appear as polygonal units with numerous irregular plates of hepatocytes converging on a central venule (C)
• Small bile ductules (D), venule (V) branches of the portal vein, and arteriole (A) branches of the hepatic artery.

Hepatic Lobule Microvasculature

Sinusoids and Key Cells

• Hepatic sinusoids: fenestrated endothelial lining
• Kupffer cells: phagocytose RBCs, antigens, debris
• Hepatic stellate (Ito) cells: store vitamin A, ECM production, myofibroblast transformation in injury

Bile Canaliculi

• Canaliculi: tiny channels between hepatocytes for bile flow
• Form bile canaliculi network → canals of Hering → bile ductules
• Bile flow: center → periphery (opposite to blood flow)

Hepatocyte Cytoplasmic Organization

• (2) Potentially toxic compounds bilirubin (bound to albumin) and bile acids are taken up from the perisinusoidal space, processed by enzymes in the tubulovesicular system of the SER, and secreted into the bile canaliculi.
• (3) Glucose is taken up from the perisinusoidal space and stored in glycogen granules, with the process reversed when glucose is needed.

Bile Ductules

• Near the periphery of each hepatic lobule, many bile canaliculi join with the larger bile canals of Hering, which are lined by cuboidal epithelial cells called cholangiocytes. These canals soon join the bile ductules in the portal areas and drain into the biliary tree.

Hepatic Acinus Zones

• Zone I (periportal): highest O₂, active protein synthesis
• Zone II: intermediate
• Zone III (centrilobular): lowest O₂, lipid metabolism, drug detoxification, ischemic injury site

Cirrhosis

• Chronic liver injury → fibrosis & stellate cell activation
• Disrupts hepatocyte- sinusoid exchange
• Leads to hypoalbuminemia, clotting issues

Fatty Liver Disease (Steatosis)

• Triglyceride accumulation in hepatocytes
• Linked to alcohol, obesity
• Can progress to steatohepatitis, fibrosis

Neonatal Jaundice

• Due to immature hepatocyte SER & low bilirubin conjugation
• Treated with blue light phototherapy
• A frequent cause of jaundice in newborns is an underdeveloped state of the hepatocyte SER (neonatal hyperbilirubinemia).
• A treatment in these cases is exposure to blue light from ordinary fluorescent tubes, which transforms unconjugated bilirubin into a water-soluble photoisomer that can be excreted by the kidneys

Liver Regeneration

• Strong regenerative capacity via hepatocyte mitosis
• Compensatory hyperplasia after injury/ resection
• Role of liver stem (oval) cells in severe injury

Malignant Liver Tumors

• Most malignant tumors of the liver derive from hepatocytes or cholangiocytes of the hepatic ducts.
• The pathogenesis of liver carcinoma is associated with a variety of acquired disorders, such as chronic viral hepatitis (B or C) and cirrhosis

Biliary Tract & Gallbladder

• Bile from hepatocytes → bile canaliculi → ducts → gallbladder/duodenum
• Gallbladder: stores/ concentrates bile
• CCK stimulates bile release after fatty meals

Gallbladder

• The gallbladder consists of a saclike structure that stores and concentrates bile, and releases it into the duodenum after a meal

Bile Ducts

• Bile leaves the liver in the left and right hepatic ducts (1), which merge to form the common hepatic duct, which connects to the cystic duct serving the gallbladder.
• The latter two ducts merge to form a common bile duct (2).
• All these ducts are lined by cuboidal or low columnar cells called cholangiocytes, similar to those of the small bile ductules in the liver.
• The main pancreatic duct merges with the common bile duct at the hepatopancreatic ampulla, which enters the wall of the duodenum at a major papilla (of Vater) (3).
• The accessory pancreatic duct enters the duodenum at a minor papilla.
• Bile and pancreatic juice mix before their release into the duodenum at the major papilla (4)

Gallstones (Cholelithiasis)

• Excess cholesterol or bilirubin in bile → stone formation
• Can cause cholecystitis, bile duct obstruction

Gallstone Composition

• Gallstones are chiefly composed of cholesterol, bilirubin, calcium salts, and smaller quantities of other constituents.
• Based on the presence and amount of cholesterol, they are divided into: