Liver function
Functions of the liver:
Filtration and storage of the blood
Synthesis of bile
Detoxification
Metabolism of carbohydrates,proteins,fats,hormones
Storage of vitamins and iron eg vitamins
B12,D,K,copper and iron- Excess iron- stored as
ferratin in the liver
Formation of coagulation factors
Liver receives nutrient rich blood from GI tract via hepatic portal vein
Toxins received through blood will be chemically modified through detoxification
Pressure into the liver via hepatic vein=9mmHg
Pressure leaving the liver via the vena cava=0 mmHg
=resistance to blood flow through hepatic sinusoids=low
Liver is expandable- large quantities of blood can be stored
Resevoir of blood=in excess blood volume
Source of blood- in diminished blood volume
Liver lobule=functional unit of the liver
Liver lobule:
Assembled around a central vein
Empties into the hepatic vein-vena cava
Space of disse-perisinusoidal spaces- connect with lymphatic vessels
Endothelium has Large pores- substances can move freely into the space
and out
Excess fluid in removed from the space of disse through lymphatics
Kupffer cells- resident macrophages that line the sinusoids
Remove aging erythrocytes and particulate matter from the blood
Healthy liver- tolerogenic phenotype- prevent undesired immune responses
Diseased liver- pathologically activated state- inflammation, hepatocellular injury and
damage
Absence/lowered function- increased pathogen invasion and systemic inflammation
Activation-uncontrolled state
Transport
Blood- space of disse- hepatocytes
Hepatocytes- secretory epithelial cells- exchanges solutes from the space of disse-bile
canaliculi
, Can uptake, metabolise and excrete a wide range of solutes
Processing of compounds:
Uptake from the blood across the sinusoidal membrane
Transport within the cell
Control chemical modification/degradation
Export into the bile across the canalicular membrane
Stellate cells- vitamin A storage
Morphologically-large lipid droplets
Upon injury myofibroblast phenotype
Fibrogenesis
Type 1 Collagen deposition
Production of cytokines
Remodelling of the ECM
=cirrhosis
Alcohol:
Upregulates factors which activate
Stellate cells
Kuppfer cells
Hepatocytes
Production of cytokines and chemokines
Increased IL-8
Decreases proteasome activity
Increase ROS
Formation of protein adducts- serve as antigens
=accumulation of T and B cells
Cholesterol metabolism
Acetyl coA- derived from glucose,fatty acid and amino acids catabolism
Acetyl CoA-HMG coA- mevalonate-cholesterol-VLDL-IDL-LDL-HDL
HMG coA reductase- enzyme
Lipoproteins- transport vehicles for moving water-insoluble lipids around the body
HDL-Picks up excessive cholesterol to the liver for use/disposal
LDL-delivers cholesterol to tissues (BAD CHOLESTEROL)
Primary Bile acids synthesised directly from cholesterol
Dehydroxylated by bacteria in the terminal ileum and colon- secondary bile acids
Enterohepatic circulation:
Bile acids secretion
Reabsorption
Return to the liver in portal blood
Functions of the liver:
Filtration and storage of the blood
Synthesis of bile
Detoxification
Metabolism of carbohydrates,proteins,fats,hormones
Storage of vitamins and iron eg vitamins
B12,D,K,copper and iron- Excess iron- stored as
ferratin in the liver
Formation of coagulation factors
Liver receives nutrient rich blood from GI tract via hepatic portal vein
Toxins received through blood will be chemically modified through detoxification
Pressure into the liver via hepatic vein=9mmHg
Pressure leaving the liver via the vena cava=0 mmHg
=resistance to blood flow through hepatic sinusoids=low
Liver is expandable- large quantities of blood can be stored
Resevoir of blood=in excess blood volume
Source of blood- in diminished blood volume
Liver lobule=functional unit of the liver
Liver lobule:
Assembled around a central vein
Empties into the hepatic vein-vena cava
Space of disse-perisinusoidal spaces- connect with lymphatic vessels
Endothelium has Large pores- substances can move freely into the space
and out
Excess fluid in removed from the space of disse through lymphatics
Kupffer cells- resident macrophages that line the sinusoids
Remove aging erythrocytes and particulate matter from the blood
Healthy liver- tolerogenic phenotype- prevent undesired immune responses
Diseased liver- pathologically activated state- inflammation, hepatocellular injury and
damage
Absence/lowered function- increased pathogen invasion and systemic inflammation
Activation-uncontrolled state
Transport
Blood- space of disse- hepatocytes
Hepatocytes- secretory epithelial cells- exchanges solutes from the space of disse-bile
canaliculi
, Can uptake, metabolise and excrete a wide range of solutes
Processing of compounds:
Uptake from the blood across the sinusoidal membrane
Transport within the cell
Control chemical modification/degradation
Export into the bile across the canalicular membrane
Stellate cells- vitamin A storage
Morphologically-large lipid droplets
Upon injury myofibroblast phenotype
Fibrogenesis
Type 1 Collagen deposition
Production of cytokines
Remodelling of the ECM
=cirrhosis
Alcohol:
Upregulates factors which activate
Stellate cells
Kuppfer cells
Hepatocytes
Production of cytokines and chemokines
Increased IL-8
Decreases proteasome activity
Increase ROS
Formation of protein adducts- serve as antigens
=accumulation of T and B cells
Cholesterol metabolism
Acetyl coA- derived from glucose,fatty acid and amino acids catabolism
Acetyl CoA-HMG coA- mevalonate-cholesterol-VLDL-IDL-LDL-HDL
HMG coA reductase- enzyme
Lipoproteins- transport vehicles for moving water-insoluble lipids around the body
HDL-Picks up excessive cholesterol to the liver for use/disposal
LDL-delivers cholesterol to tissues (BAD CHOLESTEROL)
Primary Bile acids synthesised directly from cholesterol
Dehydroxylated by bacteria in the terminal ileum and colon- secondary bile acids
Enterohepatic circulation:
Bile acids secretion
Reabsorption
Return to the liver in portal blood
