see also:

• liver diseases
• assessment of hepatic function
• liver function tests (LFTs)
• jaundice (icterus)
• hepatomegaly
• hepatosplenomegaly
• steatohepatitis (fatty liver)
• cirrhosis
• prescribing drugs in patients with liver impairment
• hepatic encephalopathy
• hepatocellular carcinoma

• the adult liver normally weighs ~1.5kg
• it has a dual blood supply, both vessels entering the liver via the porta hepatis hilum on the under surface of the liver in the transverse fissure:
  • 60-70% provided by the portal vein
  • 30-40% provided by the hepatic artery
• branches of these vessels along with bile ducts form portal ducts which branch out into 17-20 orders of branching throughout the liver
• the transit time for blood to pass from the portal venule through the sinusoids of the hepatic lobule and into the central hepatic vein is ~8 seconds
• the liver has a lobular architecture:
  • a hepatic lobule is hexagonal in cross section and consists of:
    • 6 triangular acini which drain into a central hepatic vein
    • each pair of acini have a portal duct system on its perimeter
    • each acinus can be divided into 3 zones of distance from the portal duct blood supplies and contain hepatocytes organised into a one cell thick cribriform plate pattern

• the liver receives the venous blood from the GIT via the portal vein
• numerous phagocytic macrophages (Kupffer cells) line the sinusoids and are a primary defence against pathogens derived from the GIT
• excess glucose is converted by the liver into glycogen stores

• this is commonly achieved through conjugation with glucuronyl transferase in a similar manner to bilirubin
• toxins
• steroids
• hormones
• medications
• etc

• the liver produces bile which passes into the hepatic ducts into the common bile duct which transports it to the duodenum to aid digestion of foods, and to the gall bladder for storage
• liver bile is an alkaline electrolyte solution resembling pancreatic juice and is 97% water but also consists of:
  • bile salts
    • reduce surface tension
    • emulsify fats to aid digestion and absorption in the small intestine (aided by monoglycerides and phospholipids)
      • as they tend to form micelles at certain concentrations, these micelles are important for keeping lipids in solution and they can then be transported across the intestinal brush border epithelium - most are absorbed in the terminal ileum via Na⁺-bile salt co-transport system
    • they are the sodium and potassium salts of bile acids conjugated with cysteine derivatives - glycine or taurine
      • primary bile acids are synthesized in the liver from cholesterol at a rate of 0.2-0.4g/d:
        • cholic acid 50%
        • chenodeoxycholic acid 30%
      • secondary bile acids are synthesized by intestinal bacteria from the 5-10% of primary bile acids which make it to the colon:
        • deoxycholic acid 15% - the salts are mostly reabsorbed in the colon
        • lithocholic acid 5% - 99% of these salts are excreted as they are quite insoluble
  • bile pigments
    • bilirubin - the main breakdown product of haemoglobin
      • most is formed in the tissues by the breakdown of Hb and is then transported to the liver bound to albumin
      • free bilirubin enters hepatocytes where it binds to cytoplasmic proteins and then is conjugated with glucuronic acid catalyzed by glucuronyl transferase in the smooth endoplasmic reticulum to form the more water soluble bilirubin diglucuronide which is actively transported into the bile canaliculi (some escapes into the blood “conjugated biluribin” and this is excreted in urine as it binds to albumin less than free bilirubin does). Most of the conjugated bilirubin enters the intestines where it is is poorly absorbed by intestinal epithelium but instead is converted by bacteria to colourless urobilinogens which then can be absorbed as part of the entero-hepatic circulation while some reach systemic circulation when it can be excreted in urine.
      • see also jaundice (icterus)
    • biliverdin
  • other substances
    • cholesterol
    • alkaline phosphatase
    • steroid hormones (enter enter-hepatic circulation)
    • conjugated drug metabolites
• ~500mL is secreted each day
  • substances which stimulate bile secretion are called “choleretics”:
    • bile salts - these are among the most important physiologic choleretics
    • vagal nerve stimulation
    • secretin
• some are reabsorbed in the intestine (esp. the terminal ileum) to be re-used by the liver (“enter-hepatic circulation”)
  • without a enter-hepatic circulation, the liver cannot sufficiently replace bile salts
• without bile, half of ingested fats will be excreted in stool resulting in steatorrhea and malabsorption of fat soluble vitamins

• stores bile when the sphincter of Oddi is closed (it opens when food enters the mouth)
• the bile becomes concentrated by absorption of water to ~89% water
• the gall bladder also acidifies the bile reducing pH from 7.8-8.6 down to 7.0-7.4
• substances which stimulate GB contraction (usually via CCK release which also opens the sphincter of Oddi) are called “cholagogues” such as duodenal fatty acids and amino acids
• cholelithiasis
  • cholesterol stones form when there is a nucleation factor in super-saturated bile that is sequestrated in the GB (rather than flowing)
  • cholesterol is quite insoluble in bile and requires the correct balance of bile salts and lecithin to keep it in micellar solution
  • stones take at least 2-3 weeks to form in bile
• cholecystectomy
  • results in a constant flow of bile to the sphincter of Oddi and dilatation of the common bile duct
  • flows still tend to be somewhat increased after meals but very high fat intakes may be problematic in exceeding bile capacity resulting in steatorrhoea

• liver is the main production factory of the body producing:
  • albumin
  • clotting factors
  • steroid binding proteins
  • hormone binding proteins
  • acute phase proteins in response to systemic circulating cytokine signals, in particular, IL-6
  • other proteins

• glucose to maintain blood glucose levels via gluconeogenesis and glycogenolysis
• amino acids
• lipids
  • fatty acids
  • cholesterol
  • lipoproteins
• fat soluble vitamins
• water soluble vitamins