What is the largest visceral organ
Liver 1.5 kg
What is the importance of the liver
detoxifies blood, processes nutrients, and produces bile and proteins essential for digestion and clotting.
What is the hepatic lobule
Hexagonal functional unit of liver that filters blood and produces essential substances like bile.
What cells are in the liver
Hepatocytes(60%) - perform most metabolic functions
Kupffer cells- type of tissue macrophage found in sinusoids
liver sinusoidal endothelial cells (LSEC)
What are LSECs
specialised porous liver vessel cells that filter waste and regulate nutrient exchange between blood and liver tissue.
What do hepatocytes synthesise
blood clotting factors -
Fibrinogen
Prothrombin
Nearly all the other factors e.g. V, VII, IX, X, XII, C
What are hepatocytes storage functions
Important depots for storage of fat-soluble vit A, D, E and K Vit
Stores Vit B12 and enough stored to last 2-3 years
Stores folate, which is required in early pregnancy.
How is bile synthesised?
Cholesterol → converts to bile acids in hepatocytes
Conjugation with glycine/taurine → bile salts (more water-soluble)
Secreted into canaliculi → mix with bilirubin + phospholipids to form bile
How is bile secreted
Triggered by the hormone cholecystokinin (CCK) during a meal.
What is the gallbladder’s function
stores about 30-50ml bile; has neural & hormonal control
How are gallstones formed
imbalance in the chemical make-up of bile inside the gallbladder
What is jaundice
the yellowing of the skin and the whites of the eyes due to an excess of bilirubin in the bloodstream.
What is the livers central role in metabolism
To maintain blood glucose
Regulation of fat metabolism
Regulation of protein metabolism-urea formation
Cholesterol synthesis and excretion
Synthesis of specialized molecules-bile acids
Where does the liver receive blood from
gastrointestinal tract via the portal vein
What are the 2 routes of metabolism of ethanol
Oxidation through the activity of alcohol dehydrogenase (90%)
Microsomal oxidation using cytochrome P450 (10-20%)
What happens in the first step of metabolism of ethanol
Ethanol → Acetaldehyde
Enzyme: Alcohol dehydrogenase (ADH)
Location: Cytosol
Cofactor: NAD⁺ → NADH
What happens in the second step of metabolism of ethanol
Acetaldehyde → Acetate
Enzyme: Aldehyde dehydrogenase (ALDH)
Location: Mitochondria
Cofactor: NAD⁺ → NADH
What happens in the third step of metabolism of ethanol
Acetate → Acetyl-CoA
Enzyme: Acetyl-CoA synthetase
What happens in the fourth step of metabolism of ethanol
Acetyl-CoA enters metabolism
Used in Krebs cycle or fat synthesis
Name 3 factors of acetylaldehyde
highly reactive
can inhibit enzyme function.
In the liver this can lead to a reduction in the secretion of both serum protein and VLDL - results in fatty liver
What are the 3 stages of alcohol liver damage
1)Fatty liver
2)alcoholic hepatitis, groups of cells die resulting in inflammation
3)Cirrhosis which includes fibrosis, scaring and cell death
What ate the consequences of high ethanol metabolism
High NADH inhibits gluconeogenesis
and stimulates lactate production causing lactate acidosis
stimulates fatty acid synthesis
inhibits TCA cycle
What are xenobiotics
compounds with no nutritional value e.g plant metabolites, cosmetics and food additives
What is the livers role in xenobiotic metabolism
to make xenobiotics harmless and more readily disposed of by the kidney in urine or the gut in faeces
