Hepatocytes and Bile

HEPAT OCYTES AND BILE Hepatocytes • • • • • 5-12 sided polygonal cells 2 domains: o Lateral domains form bile canaliculi conveying bile to periphery of the classical lobules o Sinusoidal domains: ▪ Have microvilli that project into the space of Disse ▪ Facilitate the exchange of material between the hepatocyte and the plasma Manufacture bile and endocrine secretion o Protein synthesis ▪ Free ribosomes ▪ RER ▪ Golgi complex: each cell has several sets of Golgi apparatuses, located near bile canaliculi ▪ Mitochondria: up to 2000 ▪ SER: for detoxification in cisternae of SER • Greater number of SER in zone 3 Inclusions o Lipid droplets: VLDLs o Glycogen varies depending on: ▪ Location i.e. more in zone 1 of liver acinus and fewer in zone 3 ▪ Fasting state Lipid metabolism o CMs released by surface absorbing cells of small intestine → reach liver via common hepatic artery • o Hepatocytes remove CM remnants from space of Disse o CMs are degraded into FAs and glycerol Carbohydrate storage o Source and sink for glucose ▪ High glucagon → glucose liberation from glycogen ▪ Glycogenolysis ▪ Gluconeogenesis ▪ Hepatocytes also synthesize glucose from other sugars o Insulin ▪ Promotes glycogen synthesise and inhibits glycogen breakdown ▪ Inhibits gluconeogenesis ▪ Promotes lipogenesis ▪ Stimulates protein synthesis Bile • • • • 600-1200ml bile/day Watery fluid containing: o Bile salts o Bilirubin glucuronide (bile pigment) o Phospholipids, lecithin, cholesterol o Plasma electrolytes e.g. sodium, bicarbonate Function: o Sole excretory route for solutes not excreted by kidneys i.e. cholesterol, bile pigments, drugs, metabolites o Bile salts and acids promote dietary lipid absorption (supply micelle forming properties) Enterohepatic recirculation of bile salts o Secretion → intestinal reabsorption → portal blood o 12-36g/day secreted but only 600mg/day produced o Denovo synthesis starting in SER by conjugation of cholic acid to taurine or glycine → cholic acid and chenodeoxycholic acid o Bile collects in canaliculi → ductules → interlobular bile ducts → hepatic duct o o CBD transports bile directly to the duodenum or diverts it to the gall bladder via cystic duct Sodium transport through epithelium is responsible for bile concentration Cells of the liver • • Cholangiocytes are epithelial cells of bile duct o Morphology of cells changes along tract o Cuboidal to columnar and mucus secreting as approach porta hepatis o Modify bile by water reabsorption o Secretin from diffuse neuroendocrine system promotes secretion of bicarbonate fluid Endothelial cells o Highly fenestrated o Facilitate movement of molecules between blood and Space of Disse o Pores are dynamic e.g. enlarge in response to increased pressure and low O2, decrease in response to noradrenaline • • • • Kupffer cells: hepatic phagocytic system o Found in sinusoids o Mostly fixed macrophages (checkpoints) → positioned to scavenge bacteria o Major cellular system for the removal of undesirable particulate matter and expired RBCs ▪ Portal blood is subject to bacterial invasion → Kupffer cells rapidly phagocytose bacteria Ito (hepatic stellate) cells o Liver-specific pericyte (cells around capillary) o Fat storing cells lining sinusoids o Store and accumulate vitamin A o Synthesize ▪ Extracellular matrix molecules (ECM) ▪ Extracellular matrix degrading metalloproteinases ▪ Cytokines and growth factors In response to cellular stress, Ito cells transdifferentiate into a myofibroblastic phenotype Pit cells o o o o o Liver specific natural killer T cells (innate immune system) ▪ Natural killer (NK) cells attack certain tumour cells, virus infected cells, bacteria, parasites ▪ NK cells also found in spleen, lung, intestine, lymph and bone marrow Found in sinusoids Activated by Ito cells May contact Kupffer cells Pseudopdia of pit cells can pass through fenestrations and through space of Disse ▪ Lysosomal enzymes Lymph production (~½ in liver) • • • • Fluid and protein in blood flow into space of Disse Lymph flows through space of Disse to collect in small lymphatic capillaries associated with portal triads If pressure in the sinusoids increases much above normal, there is a corresponding increase in the rate of lymph production In severe cases the liver literally sweats lymph which accumulates in the abdominal cavity as ascitic fluid