Normal Liver Physiology Flashcards
Describe the bloody supply to the liver
70% blood via hepatic portal vein:
- Superior mesenteric vein: Small intestine, large intestine, stomach and pancreas
- Splenic vein: spleen, stomach, pancreas and large intestine
30% of blood from hepatic artery (from AA)
Describe the venous drainage of the liver
Hepatic veins to the inferior vena cava
What makes up the splanchnic circulation?
Blood flow through the stomach, small and large intestines, pancreas, spleen and liver.
How are products exported by the hepatocytes?
Some metabolites excreted across the same membrane that they entered the hepatocyte through, into the central vein and IVC to be exported via kidneys.
Others (large drug metabolites) are excreted through the canalicula membrane into the bile duct to enter the gall bladder, small intestine and be excreted in faeces. Constituents of bile also excreted in this way.
Describe the functional zones of liver lobules
Zone 1: periportal hepatocytes, most oxygenated: specialise in oxidative metabolism, gluconeogenesis and urea synthesis.
Zone 2: intermediate properties
Zone 3: pericentral hepatocytes, least oxygenated: specialise in drug metabolism, glycolysis and lipogenesis.
What type of cell surrounds each lobule?
Reticuloendothelial cells
What types of cells exist in the liver?
Hepatocytes
Cholangiocytes
Reticuloendothelial cell mesh:
- Endothelial cells
- Kupffer cells
- Lipocytes (stellate cells)
What cells exist in the space of Disse?
Lipocytes (stellate cells)
What are the functions of the cholangiocytes?
Line the bile duct
Secrete HCO3- ions and water into the bile
What are the major functions of the liver?
Energy metabolism and substrate interconversion Synthesis of plasma proteins Drug metabolism and detoxification Immune functions Production of bile Cholesterol processing Storage of vitamins and minerals Excretion of bilirubin
What roles does the liver play in energy metabolism and substrate interconversion?
Carbohydrate metabolism
- Glycogenolysis
- Gluconeogenesis
- Glycogen synthesis
- Glycolysis, citric acid cycle and fatty acid synthesis
Lipid metabolism:
- Ketogenesis
- Triglyceride synthesis from fatty acids
Protein metabolism:
- Deamination
- Urea formation
What plasma proteins does the liver synthesise?
Major plasma proteins: albumin
Factors involved in haemostasis and fibrinolysis:
Fibrinogen (coagulation), coagulation inhibitors (e.g. alpha1 anti-trypsin), plasminogen (fibrinolysis)
Carriage proteins:
- e.g. transferrin
- sex hormine bnding globulin (SHBG)
- thyroid-binding globulin (TBG)
Pro-hormones, apolipoproteins
What is the function of albumin?
Maintains the osmotic pressure of the plasma
Transports substances in blood
What is the role of Kupffer cells in the liver?
Tissue macrophages located in hepatic sinusoids attached to endothelial cell lining..
Ingest bacteria and inflammatory mediators by phagocytosis.
Describe the process of production, storage and secretion of bile
Bile is produced by the liver and exported into the gall bladder where it is concentrated (by removing water and salts from the organic molecules in bile) and stored.
Released from the gall bladder via the bile duct into the duodenum during eating.
What stimulates the contraction of the gall bladder to eject bile into the duodenum?
Cholecystokinin (CCK)
How do cholecystokinin (CCK) and secretin work?
In response to the stomach emptying its contents, walls of the intestine secrete CCK and secretin.
Secretin: acts on exocrine pancreas to stimulate secretion of bicarbonate ions. Acts on the liver to stimulate bile production.
CCK: Acts on the exocrine pancreas to secrete enzymes into the small intestine. Also stimulates gallbladder contraction to release bile into the duodenum.
What are the 6 major components of bile and their roles?
Bile salts conjugated with taurine (solubilise fat in small intestine)
Lecithin (a phospholipid)
HCO3- and other salts (neutralises acid in duodenum)
Cholesterol
Bile pigments and metabolic end products
Trace metals
What are the functions of bile?
Solubilise dietary fat in small intestine (carried out by bile salts)
Neutralises acid in duodenum (by HCO3- secretion)
How are bile salts formed?
Primary bile acids synthesised from cholesterol and conjugated with taurine or glycine.
Secondary (recycled) bile acids are conjugated with glycine. This forms bile salts which are transported out of the hepatocyte across the canalicula membrane via the bile canaliculus into the bile duct.
Describe the enterohepatic circulation
Bile salts are released into the small intestine.
95% are recycled in the terminal ileum and returned to the liver via the portal circulation.
-75% are recycled as intact bile salts
-25% are deconjugated (taurine or glycine removed) by bacteria in the terminal ileum and colon to yield primary bile acids.
–Some of these are dehydroxylated by bacteria to yield secondary bile acids
(primary and secondary bile acids are both recycled- re-conjugated in the liver)
-5% are excreted in faeces - the liver synthesised new bile salts to replace them.
What hormones are secreted into the small intestine upon the emptying of stomach contents?
Cholecystokinin (CCK) and Secretin
What do hepatocytes secrete?
Bile salts
Cholesterol
Lecithin
Bile pigments
How does the liver export excess cholesterol not used to make bile salts?
Excess cholesterol is removed from the hepatocytes and exported across the canalicula membrane to be exported in faeces
