6. Liver Flashcards
What are the main functions of the liver?
- Metabolic and catabolic
- Secretory and excretory
- Detoxification and immunological
What is bile secreted by the liver used for?
- Emulsification and absorption of fats
- Cholesterol homeostasis
- Toxin excretion - endogenous e.g. bilirubin, and exogenous
- Secondary absorption of lipid-voluble vitamins (ADEK)
Describe the macroanatomy of the liver
• 2 lobes (left and right)
- separated by falciform ligament
• Dual blood supply - hepatic artery and hepatic portal vein
• Each lobe is split into segments
- I => VIII
- IV split into a and b (upper and lower)
• Each subsection drains into its own vein
• Left, middle and right hepatic vein => Vena Cava
What is the hepatic lobule?
• Structural unit • Hexagonal • Each corner = portal triad (linkage of 3 adjacent lobules) • Central vein runs through the centre - collects blood from hepatic sinusoids • Rows of hepatocytes within lobules - sinusoid and canaliculi facing side
What does the portal triad consist of?
• Branch of hepatic portal vein - 80% of blood
- mixed venous blood from GI organs and spleen
- hepatocytes process nutrients, detoxify blood and excrete waste
• Branch of hepatic artery
- 20% of perfusion
- oxygen-rich blood
- supports hepatocyte high energy demands
• Bile ducts
- bile produced by hepatocytes
- bile canaliculi => cholagiocyte-lined bile ducts
(blood flows towards centre, bile flows towards perimeter)
What are sinusoids?
- Specialised capillaries
- Wider than normal
- Allow blood to flow slower
- Fenestrated
- Space of Disse - extravascular space of plasma between sinusoids and hepatocytes
What are Kuppfer cells?
- Sinusoidal macrophages
- Phagocytose bacteria
- Release cytokines to activate hepatic stellate cells in the Space of Disse
- Stellate shaped and high in number
- Attached to endothelial cells
What are hepatic stellate cells?
- Quiescent state (dormant)
- Store Vitamin A in liver cytosolic droplets when inactive
- Activated via liver damage or Kuppfer cells => fibroblasts
- Proliferate and deposit collagen in ecm
- Too much => fibrosis/cirrhosis
Describe the function hepatocytes (including what they produce and contain)
• 80% of liver mass • Cubical • Synthesise: - albumin - clotting factors - bile salts • Contain: - glycogen - lysozymes - cytoplasmic enzymes - peroxisomes • Drug metabolism • Receive nutrients • Secrete bile into bile canuliculi
What are cholangiocytes?
• Secrete bicarbonate and water to form bile
Describe the anatomy of the biliary system in the liver?
- Bile canaliculi
- Small ductules
- Small bile ducts
- Larger bile ducts
- Right/left hepatic ducts
- Common hepatic duct
- cystic duct => common bile duct
- Pancreatic duct (at the Ampulla of Vater)
- Duodenal papilla
What is bile made up of?
- Cholesterol
- Bile salts
- Bilirubin and drug metabolites
Summarise the production of bile?
• Hepatocytes - 60% of bile - primary secretion • Cholangiocytes - 40% of bile - secondary modification - reabsorption and secretion - pH alteration, HCO3- secretion, sugar/acid reabsorption - IgA exocytosed into bile
Describe the structure of a micelle
• Hydrophilic bile salts face out • Hydrophobic bile salts face in - reduce surface tension • Phospholipids on outside • Water and soluble fats condensed in lipid core
What are the bile acids?
• 2 primary acids - cholic acid - chenodeoxycholic acid • 2 secondary acids (made from primary acids via cut bacteria) - deoxycholic acid - lithocholic acid
What is the function of the gall bladder?
- Small muscular storage organ
- Can store 50ml of bile
- Modifies bile - reabsorption via endothelial cells
- Concentrates bile - reabsorbes water
What is eneterohepatic circulation?
- Substances cycling between gut and liver
- Continuous reabsorption in gut
- Recycling of bile salts
Outline carbohydrate metabolism in the liver
- Liver stores carbohydrates as glycogen
- Glycogen => glucose when glucose drops
- 24hr fast - lactate => pyruvate => glucose to muscle (6ATP)
- Gluconeogenesis via deamination and triglycerides too
Outline protein metabolism in the liver
• Transamination (switching amine group to a ketoacid)
• Makes a ketoacid - usually pyruvic acid
• Glutamic acid made - common intermediate for many amino acids
• Deamination - carbohydrate skeleton as an energy source, muscle liberates alanine and liver converts it into glucose
• Liver convert ammonia (NH3) to urea
- NH3 is highly toxic to CNS
- urea is water soluble and non-toxic
Outline fat metabolism in the liver
- Stored in adipose tissue and liver
- Full glycogen - glucose => fat storage
- Metabolism - fatty acids => acetyl CoA (TCA cycle)
- Triglyceride in adipose tissue => fatty acids
- Fatty acids enter liver => acetyl CoA via beta-oxidation
- Can become ketone body or TCA cycle
- 2 acetyl-CoA => acetoacetate
- Thiophorase in skeletal muscle and brain (not liver) allows it to be used there
• Liver also synthesises lipoproteins, cholesterol and phospholipids
• Lipoprotein synthesis allows for easy transport in blood
- VLDL - lots of triglyceride
- LDL - high cholesterol and phospholipids
- HDL - high protein
What does a lack of vitamin B12 cause?
- Pernicious anaemia
* Nerve demyelination
How does synthesis of cholesterol occur?
- In liver
* Begins with 2x acetyl-CoA in the mevalonate pathway
