Editing Liver (section)

== '''Functions''' ==

* Energy
** Glycogenolysis from glycogen      and gluconeogenesis from lactate pyruvate, glycerol, propionate, and      alanine
* Blood flow
** Portal pressure is normally      6-10mmHg and sinusoidal pressure is normally 2-4mmHg
** Arteriolar tone is regulated      by autonomic nervous system, circulating hormones, bile salts, and      metabolites
** Hepatic arterial flow can be      increased to compensate decreased portal vein flow, but the opposite does      not occur
** Total portal vein occlusion      cannot be fully compensated by the hepatic artery, leading to ipsilateral      atrophy
* Bile formation
** Bile is used to dispose of      secreted substances and to provide enteric bile salts to aid in digestion      of fats, and absorption of fat-soluble vitamins (ADEK) and lipophilic      drugs
** Secreted by hepatocytes into      canaliculi
** 1500mL of bile is secreted      daily, and 80% of this is secreted by hepatocytes into canaliculi      (largely the result of water flow in response to active solute transport.
** Bile flow has a linear      relationship with bile acid secretion, known as bile acid-dependent flow
** Epithelial cells of the      biliary tract continue to actively reabsorb and secrete water and      electrolytes into and from bile, but usually with a net secretion,      accounting for the other 20% of biliary secretion
** Gallbladder acts as the      reservoir of the biliary tree - function is to store bile in the fasting      state
** The gallbladder reabsorbs      water, concentrating stored bile, and secretes mucin
** Bile contents
***
*** Osmolality is approximately       300mOsm/kg (similar to blood) and is accounted for by the inorganic       solutes
*** Major organic solutes are       bile acids, bile pigments, cholesterol and phospholipids
* Enterohepatic circulation
** Bile salts (primarily cholic      acid and chenodeoxycholic acid) are produced in the liver from      cholesterol
** These primary bile acids are      modified by intestinal bacteria to form the secondary bile acids      (deoxycholic acid and lithocholic acid), which are reabsorbed passively      in the jejunum and actively in the ileum
** After returning to      hepatocytes in the portal venous circulation, up to 90% of the bile acids      are extracted, and only a small proportion spill over into the systemic      circulation
** A small amount of intestinal      bile acids are not reabsorbed and are excreted in the stool
** This circulation is also the      major mechanism for excreting excess cholesterol
* Bilirubin metabolism
** Bilirubin-albumin complex in      blood enters the peri-sinusoidal space, and is disassociated
*** Portosystemic shunts       (cirrhosis and portal HTN) decrease first-pass hepatic clearance of       bilirubin, leading to mildly increased serum levels
** Free bilirubin is taken up      by the hepatocyte, where it is conjugated with glucuronic acid and then      secreted against a concentration gradient into canalicular bile
** The majority of conjugated      bilirubin-glucuronic acid is deconjugated within the intestine to a group      of compounds known as urobilinogens
*** The majority passes through       the GIT without reabsorption and is excreted in the stool as stercobilin
*** Some urobilinogens are       further oxidised and reabsorbed into the enterohepatic circulation. Some       is re-conjugated and cleared by the liver, and some reaches the systemic       circulation.
*** A small percentage of the       reabsorbed urobilinogens are excreted into urine - contributing to the       yellow colour of urine
* Carbohydrate metabolism
** Contains up to 65g of      glycogen/kg of liver tissue, which can be broken down through      glycogenolysis
** Between meals, the liver is      the primary source of glucose; especially important for brain and      erythrocytes, which rely on glucose for metabolism
** In fasting, liver uses      lactate to produce glucose via the Cori cycle
** During a prolonged fast,      fatty acids from adipose breakdown are beta-oxidised in the liver, which      releases ketone bodies that then become the primary fuel for the brain
** Transition between metabolic      states is mostly dependent on hormones and sinusoidal glucose      concentration
** Derangements of carbohydrate      metabolism are common in cirrhotics and liver disease in general. Only      with massive hepatocyte loss in fulminant liver failure does      gluconeogenesis fail and hypoglycaemia ensue.
* Lipid metabolism
** Fatty acids synthesised in      the liver during states of glucose excess, which are then stored in      adipose tissue
** Prolonged increased      circulating fatty acids will override the liver's ability to handle them,      resulting in fatty accumulation in the liver, known as steatosis, and      when added to chronic inflammation in more advanced states,      steatohepatitis. Diabetes, steroid use, starvation, obesity, and      chemotherapeutic agents are associated with this state.
* Protein metabolism
** Excess amino acids not used      by peripheral tissues are either oxidised for energy or converted to      other energy sources in the liver
** Ammonia, glutamine,      glutamate and aspartate are produced through catabolisation of amino      acids throughout the body, then processed in the liver, where waste      nitrogen is converted to urea in the urea cycle, and the urea is      generally excreted in the urine
** Liver is responsible for      production of albumin, ceruloplasmin, iron storage and binding proteins,      and alpha-1 antitrypsin
** Liver is also responsible      for many acute phase response proteins
* Vitamin metabolism
** Metabolism of fat-soluble      vitamins ADEK
** Vitamin is solely stored in      the liver, and overdose can result in hepatic toxicity
** Cholestasis syndromes can      result in inadequate absorption secondary to poor micellization in the      intestine
*** Metabolic bone disease (vit       D deficiency)
*** Neurologic disorders (vit E       deficiency)
*** Coagulopathy (vit K       deficiency)
* Coagulation
** Synthesises almost all the      identified coagulation factors, and for clearing coagulation products
** Hepatic synthetic      dysfunction leads to abnormal PT, mostly through inability to activate      factor VII by vitamin K in the liver
* Metabolism of drugs and     toxins
** Phase 1 reactions increase      the polarity and thus water-solubility of compounds, to allow easier      excretion, and occur in the cytochrome P450 system
** Phase 2 reactions generally      act to create a less toxic or less active by-product, generally through      transferase reactions
* Regeneration
** Hyperplastic response of all      cell types in the liver, in which the microscopic anatomy is maintained
** Maximal hepatocyte DNA      synthesis occurs 24-36 hours post-partial hepatectomy, and most of the      increase in hepatic mass is seen by 3 days in rodents, and it is usually      almost complete after 7 days
** A variety of factors have      been implicated, but many questions still remain, and we are not able to      induce hepatic growth in a normal host yet

[[Category:Anatomy]]