W4 L11: Liver & gall bladder physiology

Where is the liver in the body?
  • Largest solid organ
  • Located underneath diaphragm & v close proximity to pancreas, small intestine & gallbladder
  • Underneath liver is gallbladder
  • Gallbladder stores bile

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Structure of the gall bladder
  • Thin-walled muscular sac on ventral surface of liver & diverticulum from bile duct
  • Stores & concentrates bile
  • Contracts when there’s food in duodenum to release bile into GI tract

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Function of Liver and Gallbladder

Liver function:
  • Red blood cell (erythrocyte) turnover
  • Digestion
  • Storage
  • Detoxification
  • Hormone production
Role of liver in erythrocyte maintenance
  • Phagocytosis of old red blood cells by Kupfer (stellate reticuloendothelial) cells generating:
    • iron
    • globin
    • bilirubin
  • Storage of iron as ferritin & hemosiderin
  • After erythropoietin (Epo) release these proteins are transported to the bone marrow by transferrin, iron is released for erythrocyte precursor gen.
Influence on protein metabolism
  • Major site for protein synth.
    • plasma proteins
    • coagulation factors
    • Ca & Fe binding factors
  • Protein catabolism to generate urea
Influence on glucose metabolism

Maintenance of plasma glucose:

  • Breakdown of glycogen to glucose by glycogenolysis
  • Glycogenic amino acids broken down to generate glucose via gluconeogenesis (GNG)
  • Release glucose directly into the bloodstream

Storage of glycogen:

  • Under conditions of high blood glucose (e.g. after a meal) glucose is converted glycogen & triglycerides for storage

Β Β Liver storage:

  • glycogen
  • fat
  • steroid vits. (A, B12 & D) & vits. E & K
  • minerals iron & copper
Role of liver in lipid metabolism

Synthesis:

  • Dietary fat processed to generate very-low-density lipoproteins (VLDL) generated from triglycerides, apolipoprotein & cholestrol
  • cholesterol
  • bile salts

Breakdown:

Fatty acids are broken down to generate ATP

Storage:

Hepatocytes store some triglycerides

The liver produces Bile
  • Bile β†’ secretion of liver consisting of water, bile salts, bile pigments, cholesterol, lecithin & several ions
  • yellow, brownish or olive-green liquid
  • pH of 7.6-8.6
  • Daily secrets 250-1000mL of bile
Bile salts
  • Na or K salts of bile acids (mostly chenodeoxycholic acid or cholic acid)
  • Emulsification or fats into lipid globules β†’ uniformly distributed particles
  • Allow suspension of small lipid globules to form in aq sol. ↑ solubility
    • aids absorption of lipids following their digestion

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Detoxification by liver
  • Detoxifies many metabolites & substances e.g. alcohol
  • Excrete drugs e.g. antibiotics & sulphonamides into bile
  • Chemically Ξ” or secrete thyroid hormones & steroid hormones e.g. Oestrogen & Aldosterone

Secretion of bile:

  • multiple routes of entry of bile acids

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Role of the liver in control of digestion
Enterohepatic circulation

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Hormone that regulate digestion

Secretin

  • Secreted in response to acid in the duodenum
  • Stimulates biliary duct cells to secrete bicarbonate & H2O β†’ expands vol. of bile & ↑ flow out into intestine

Chloecystokinin

  • Fat in duodenum stim. chloecystokinin release
  • Stim. contractions of gallbladder & common bile duct β†’ delivery of bile into duodenum
Bile secretion

Pattern & control of bile secretion

  • During fasting, bile accumulates in gallbladder for conc
  • Chyme entry into small intestine & partially digested fats & proteins stim. secretion of enteric hormone which are important for secretion & flow of bile - also initiates pancreatic exocrine secretion
  • Secretin released in response to acid in duodenum
  • Cholecystokinin released in response to fat in duodenum

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  1. Bile produced by hepatocytes & secreted into bile caniliculi
  2. Secretin released in response to acid in duodenum
  3. Secretin stim. bile secretion by bile ductules - can double bile production for up to several hrs after a meal
  4. Bile drains into hepatic duct to be stored in gallbladder - where it’s concentrated
  5. Cholecystokinin released in response to fat in duodenum
  6. Emptying starts by rhythmic contractions of gall bladder wall, stim. most strongly by cholecystokinin - but also by vagal & enertic nerve stim.
  7. Effective emptying required simultaneous relaxation of Sphincter of Oddi
Liver as a gland
  • Synthesises angiotensinogen
  • Synthesis & release of thrombopoietin (TPO)
  • Synthesis & activation of vit D

Relationship b/w structure & function

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Relevance of blood pressure to liver
  • ↑ pressure in hepatic portal vein (portal hypertension)
    • leads to ↑ sinusoid pressure
  • Result β†’ fluid moves into interstitial fluid - then leaks into peritoneal space
Gall stones

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Jaundice
  • Yellowish colouration of sclera of eye, skin & mucous membranes caused by accumulation of bilirubin
  • Other symptoms: light stools & dark urine
  • 4 types include:
    • pre-haptic jaundice β†’ excess production bilirubin (high [bilirubin] in blood) β†’ Sign of haemolytic disease
    • (Intra)-hepatic jaundice β†’ prevents proper function of hepatocytes - congenital liver disease, cirrhosis or hepatitis can be a cause
    • Extra-hepatic jaundice β†’ hepatocyte function ↓ due to accumulation of bile β†’ blockage of bile drainage (gallstones or cancer)
    • Neonatal (physiological) jaundice β†’ observed commonly in newborns due to poor function in 1st week, disappears quickly β†’ treated by exposing to blue light