lecture 16 Flashcards
Reactions to Injury of the Liver - 1
What does the normal liver look like?
- reddish brown in colour
- 1.5kg
- in the right upper part of the abdomen attached to the undersurface of the diaphragm
- hidden by the ribcage
- smooth anterior surface
What are the major vessels in the liver?
- hepatic portal vein (from intestines)
- common bile duct (to intestines, stored temporarily in the gall bladder, released e.g. when eating a fatty meal)
- hepatic artery (from abdominal aorta)
- blood in portal vein and hepatic artery returns to heart via the inferior vena cava
What happens to the major vessels when they enter the liver?
- ensheathed in connective tissue that extends from the porta hepatis (entry point) (aka hilum)
- also contains lymphatics and nerves
- portal tract
- structures divide
- portal vein/hepatic artery branches = sinusoids
What are the specialised cells of the liver?
Cell types by percentage of total liver cells
- hepatocytes - 60%
- cholagiocytes (BEC) - 4.5%
- endothelial cells - 21%
- kupffer cells - 8.5%
- hepatic stellate cells - 5.5%
- pit cells (NK cells) - <1%
By relative volume of liver mass
- hepatocytes - 80%
- non-hepatocytes - 6%
- extracellular space - 14%
What are the functions of hepatocytes?
Metabolic
- glucose homeostasis
- glycogen storage
- glycogenolysis and gluconeogenesis
- lipid metabolism
- uptake of fatty acids, conversion to triglycerides and secretion of lipoproteins
Synthetic
- most plasma proteins - albumin
- clotting factors - almost all and natural anticoagulants (Antithrombin III and protein C & S)
- complement and other acute phase reactants
- specific binding proteins e.g. Fe, Cu, Vit A
- cholesterol
Storage
- glycogen, triglycerides, lipid soluble vitamins, Fe, Cu
Catabolic
- endogenous substances – hormones and serum proteins
- detoxification of foreign compounds e.g. drugs, industrial chemicals, bacterial products
- activation of drugs and foreign compounds
- removal of ammonia via urea synthesis
Excretory
- bile formation and excretion into the gut – bilirubin, IgA, bile acids, cholesterol, elimination of environmental toxins, carcinogens and drugs and their metabolites
What is the structure of hepatocytes? How do they fit in their environment?
- liver cell plates are like bricks laid out one on top of the other – a wall, muralium
- hexagonal bricks - 8 faces: 6 facing each other, attached firmly with (?) studs (attached firmly like lego)
- groove between large face, sealed with tight junctions but where the bile drains through
- forms continuous network which drains out to the bile tracts
- biliary canaliculus
- surfaces facing sinusoids are covered with microvilli for increased absorption and secretion function (SA)
What is the structure of sinusoids?
- lined by endothelial cells which have little grooves/holes in them called fenestrae (.15microns) to allow the free access of plasma and small products (certain particles and proteins) to hepatocytes = sieve plates
- kupffer cells (macrophages) on inside of sinusoid –> trap particular matter passing through the blood stream from the gut, including toxins, endotoxins and so on, clear the blood before it goes back via circulation to the heart
What is inside the space between the endothelium of the sinusoids and the hepatocytes?
- space of Disse
- collagen fibres called reticulum (important in fibrosis and chronic liver disease)
- hepatic stellate cells in sinusoidal space, between hepatocytes, contain lipids which store vitamin A (unknown why)
What do we see when we look at the 3D arrangement of liver cells?
- hepatocytes are organised in single cell thick walls (called liver cell plates)
- separated by sinusoids in space that separate the labyrinth of hepatocytes (called lakuning?)
- portal vein penetrates limiting plate and then gives off branches
- bile duct attaches to limiting plate and biliary canaliculi drain into it (canal of Hering)
Where are liver stem cells located?
canals of Hering
How much blood goes through the liver?
1L/min in portal vein
500mL/min in hepatic artery
- so 1.5L/min; massive blood flow
What does a normal portal tract lack?
inflammatory cells
How do we describe the structure of a liver?
- lobule and acinus with zones 1, 2 and 3
- 3 portal tracts around each ‘lobule’
- according to the lobular model, the liver is divided into 1- to 2mm hexagonal lobules oriented around the terminal tributaries of the hepatic vein, with portal tracts at the periphery of the lobule
- in the acinar model (more according to function), triangular shaped, bases are formed by the penetrating septal venules from the portal vein extending out of the portal tracts
- in the acinus the parenchyma is divided into three zones, zone 1 being the closest to the vascular supply, zone 3 abutting the terminal hepatic venule and most remote from the afferent blood supply, zone 2 intermediate
Why is zonation of the parenchyma an important concept?
- gradient of activity displayed by many hepatic enzymes, and the zonal distribution of certain types of hepatic injury
- zone 1 closest to blood therefore oxygen
- zone 3 prone to anoxia (e.g. when in shock, cardiac arrest)
What are the contents of a hepatocyte?
- large amounts of ER where breakdown and detoxification of compounds and so on occurs
- rough ER where protein synthesis occurs
- smooth ER with lots of glycogen
