: thin connective tissue capsule covering the liver
Lobes divided into lobules which contain hepatocytes and sinusoids hexagonal structure
Hepatocytes
are radially alligned in layers 1 cell thick and directed from the periphery of the lobule to its center
Sinusoids
are dilated capillaries that run in between the hepatocytes
Central vein
is found at the center of the lobule Þ where the sinusoids drain
Portal triads
occupy each corner of the lobule Þ portal vein (largest struct), hepatic artery (smallest of the three), bile duct (lined with cuboidal epith) and lymphatic vessels (nerves and capillaries may be found here as well) surrounded by a sheath of connective tissue (collagen type III reticular fibers)
Blood supply
Hepatic portal vein
: carries 75% of the blood supply to the liver, large intestine, and stomach which is nutrient rich but oxygen poor (collects blood from spleen, pancreas and small intestine)
Portal vein enters liver at portus hepatus and branches
Þ sends small venules to the portal triads of lobules Þ blood empties into liver sinusoids Þ sinusoids converge to the central vein Þ central veins converge to form large hepatic veins Þ empty into inferior vena cava
Hepatic artery
: carries oxygen rich blood to the liver (remaining 25% of blood supply)
Hepatic artery branches
Þ forms interlobular arteries Þ empty into liver sinusoids Þ same as above
Thus, blood from both sources mix in the sinusoids
Structural and functional liver units
Classic hepatic lobule
Þ central vein forms the center of the classic lobule with portal triads at its periphery Þ blood flows from the periphery to the center of the lobule while bile flows from the center to the periphery of the lobule
Portal lobule
Þ portal triad forms the center of the portal lobule with the central vein at its periphery Þ blood flows from the center to the periphery while bile flows from the periphery to the center
Hepatic acini (zones 1, 2 and 3) of Rappaport
Þ hepatic acinus represents a liver lobule that is divided into 3 regions based on their proximity to the distributing veins
Zone I
Þ cells closest to the vessels (portal triad) and 1st to be affected by incoming blood
Zone II
Þ cells which are 2nd to respond to blood (in between portal triad and central vein)
Zone III
Þ cells near the central vein which see blood that has already been altered by cells in zones I and II
Sinusoidal lining cells
Endothelial cells
line the sinusoids; contain fenestrae of about 100m m diameter, grouped together in sieve plates
Unlike cells of vascular endothelium, liver endothelial cells lack an underlying basement memb
Space of Disse
a subendothelial space separating the endothelial cells from the underlying hepatocytes
Kupffer cells
resident macrophages of the liver (15% of total liver cells); comprise 80-90% of total macrophages in the body; normally located in sinusoidal lumen anchored to the endothelium by a long cytoplasmic process
Predominant location is periportal, but found in every region of liver
Function
Þ remove particulate and other foreign materials from portal blood via phagocytosis
Fat-storing (Ito, stellate) cells
reside in space of Disse; contain vitamin A- rich lipid droplets
Function
Þ uptake, storage and release of retinoids; synthesis and secretion of ECM proteins (collagenase)
May be responsible for the production of collagen in hepatic cirrhosis
To produce extracellular matrix proteins, these cells undergo activation (morphologic and metabolic change) EtOH is a stimulus for activation
During activation, fat-storing cells lose retinoid stores, express receptors for fibrogenic cytokines, and transform into a cell with fibroblast-like features
Pit cells
large granular lymphocytes that play defensive roles against viral infection and tumor metastasis
Hepatocytes
parenchymal cells
Microvilli project into the subendothelial space of Disse and into the bile canaliculus
In direct contact with blood on at least two sides
Takes up bile acids and bilirubin, and secretes it into the bile canalicus (located at the junction between 2 hepatocytes)
Bile acids reabsorbed from the intestine
Bilirubin obtained from the breakdown of Hb
Cell membranes near canaliculus are firmly joined by tight junctions tight links to each other
From the bile canaliculi, bile empties thru canals of Hering to bile ducts in portal triads (lined with cuboidal epith)
Thus excrete via bile duct and reabsorb via hepatic portal vein
Þ enterohepatic circulation (decreases the need for new synthesis)
Cytology and ultrastructure
often binucleate and polyploid; contain glycogen (PAS +) and fat droplets; mito occupy 20-25% of the cell volume; SER and RER are abundant; golgi complexes are near canaliculi; lysosomes are important in the turnover and degradation of intracellular organelles; play role in receptor-mediated endocytosis of macromolecular ligands (coated pits); peroxisomes (microbodies) are also abundant
More mito and RER near portal triad area
Hepatic functions
exocrine function (bile formation and secretion); endocrine function (glucose release and uptake, hormone metabolism ie albumin, prothrombin); excretion (bilirubin via the bile); synthesis (plasma proteins, cholesterol); intermediary metabolism; drug detoxification; filter for foreign matter, bacteria, etc
Gallbladder
Left hepatic duct + right hepatic duct
Þ common bile duct Þ connects with major pancreatic duct Þ enters duodenum at the major duodenal papilla
Hollow, pear-shaped organ attached to lower surface of liver has folds that extend into the lumen
Epithelium
: simple columnar with microvilli, intercellular spaces near the base of the cells, and no goblet cells
Lamina propria
: loose irregular connective tissue (contains plasma cells, macrophages and capillaries) no glands in the mucosa
No
muscularis mucosa or submucosa
Muscularis externa
: consists of smooth muscle layer with abundant collagen and elastic fibers
External to muscularis externa is dense connective tissue with large blood vessels, lymphatics, and nerves
Adventitia
outermost connective layer where it is attached to the liver surface
Serosa
the unattached surface consisting of simple squamous epith
Functions storage and concentration of bile
Þ secreted into lumen Þ diffuses into blood capillaries
Fat in duodenum
Þ CCK secreted into bloodstream via enterochromaffin cells Þ contracts gallbladder Þ bile secreted into duodenum (smooth muscle surrounds the duct Þ relaxes Þ Sphincter of Oddi opens Þ bile enters duodenum) Þ emulsifies fat pancreas concurrently secretes trypsin
Pancreas (exocrine)
Compound acinar gland Surrounded by a loose connective tissue capsule which extends as septa between the lobules;
Pancreatic acinus
irregular cluster of secretory cells packed with zymogen granules (pancreatic enzymes proteases, lipases, amyolytic enzymes, nucleases, trypsin inhibitor amongst others); released into lumen by exocytosis); drains into intercalated duct
Pancreatic acinus
(secrete pancreatic enzymes)
Þ centroacinar cells located at center of secretory acinus (intra-acinar portion of intercalated duct) Þ intercalated ducts (secrete HCO3- and water) Þ intralobular collecting ducts Þ interlobular ducts (lined with low columnar epith) Þ main pancreatic duct (extends from head to tail of pancreas)Þ secretes alkaline, enzyme-rich fluid into duodenum
Pancreatic secretions are stimulated by neural and humoral mechanisms
Humoral = CCK (act on acinus), secretin (act on ductule)
Neural = ACh (act on acinus or ductule), GRP (act on acinus), VIP (act on acinus)
No striated ducts in the pancreas
Functions secretion of digestive enzymes and bicarbonate
Islets of Langerhans (lobule structure) are penetrated with capillaries and surrounded by acinar cells