Hepatobiliary system Flashcards
Where is the liver?
Top right hand quadrant of the abdomen
Why is the liver’s proximity to the stomach, pancreas, and duodenum relevant?
Efficiency of processes
The biliary tree
The biliary tree is a series of gastrointestinal ducts allowing newly synthesised bile from the liver to be concentrated and stored in the gallbladder (prior to release into the duodenum)
Gallbladder
Small sac under the liver that branches from the common hepatic duct
Salts and water in bile are absorbed
Concentrates the bile organic molecules (5x)
Holds between 30 – 60 ml bile
Most common cell in the liver
Hepatocytes, making up about 80%
Hepatic portal vein
brings highly nutrient rich blood to liver
Hepatic artery (??)
Brings oxygen rich blood to liver??
Functions of the liver
Storage of nutrients e.g. vitamins, glycogen, minerals
Metabolism (enzyme activation): of nearly everything from digested nutrients to toxins to drugs
Endocrine function: hormone production (insulin-like growth factor, angiotensinogen, thrombopoietin); synthesis of plasma proteins such as albumin, clotting factors etc
Exocrine function: bile acids, bilirubin, cholesterol, nutrient signalling hormones
Processing and “recycling” of haemoglobin
Discovery of bile acids
Earliest mention in Ebers Papyrus of the 16th century BCE
First chemical structures discovered in 1849 by Heinrich Otto Wieland
Bile
secretory product from liver and bile ducts
Functions of bile
Elimination of toxins, heavy metals and xenobiotics
Regulation of whole body lipid homeostasis
Bile salts stimulate peristalsis
Contributes to maintenance of duodenal pH
Signalling molecules
Cholestasis
Liver toxicity associated with bile secretion abnormalities
Bile flows back into liver and causes toxicity (I think??)
Components of bils
Bile acids (4-20mM in small intestine)
Similar electrolyte composition to plasma
Higher bicarbonate concentration
Phospholipids (Lecithin)
HCO3- and other salts
Cholesterol (around 80% is synthesises by the body and around 20% is consumed in the diet)
Bile pigments & small amounts of other metabolic end products
Trace metals (eg copper)
NB: Bile salts = sodium/potassium addition to bile acids
Main two bile acids
Chenodeoxycholic acid
Cholic acid
Biosynthesis of bile acids
Cholesterol -> Cholic acid or Chenodeoxycholic acid
She’s going really fast check the pathways and stuff later I’m lost
Primary bile acids - synthesised in the liver
Secondary bile acids - by intestinal bacteria
Bile’s role in lipid digestion
Emulsification and digestion of dietary triglyceride by lipase/colipase in the presence of bile acids
Formation of micelles in the presence of bile acids and movement of micelles to the enterocyte brush border
Cellular metabolism, chylomicron formation and entry into lymph
Dietary fat
component of diet extracted by organic solvents
Non-polar dietary lipids
Cholesteryl ester, hydrocarbons and carotene
Polar dietary lipids
Insoluble non-swelling amphiphiles
Insoluble swelling amphiphiles
Soluble amphiphiles
Insoluble non-swelling amphiphiles
Triacylglcyerol (triglycerides)
Diacylglycerol
Nonionized long-chain fatty acids
Cholesterol
Fat soluble vitamins
Bile acids - role in lipid digestion
Soluble amphiphiles that solubilise polar lipids during digestion
Absorption of dietary lipids
Bile acids are amphipathic
Polar and non-polar faces
Anti-bacterial properties
Denaturing proteolysis
pH for enzyme function e.g. lipase/colipase
Lipid digestion - emulsification
Fats in ingested food are insoluble in water
Aggregate into large lipid droplets
Stomach major site of emulsification
Intestinal aggregates are 0.5 μm in diameter
Emulsification:
Mechanical disruption of lipid droplets
Emulsifying agents – bile acids
Lipid digestion - micelle formation
Emulsion droplets require further breakdown
Bile salts play a role in formation of micelles (4-7 nm in diameter)
Lipid molecules released from micelles diffuse into intestinal epithelium
Importance of micellar solubilisation
Intestinal brush border
Separated from bulk fluid phase by unstirred water layer
Access across unstirred layer by diffusion
Solubility of lipids is low so few gain access to the epithelium
Micellar solubilisation increases aqueous concentration
Rate of diffusion slower but more efficient in mixed micelles containing fatty acids
Bilirubin metabolism
Biliverdin is water soluble, bilirubin is not
Bilirubin mops up free radicals
Bilirubin transported in complex to avoid excretion in urine
Liver conjugates bilirubin (glucuronyl transferase) – water soluble
Bacteria deconjugate bilirubin in the gut
Most urobilinogen absorbed, stercobilin excreted in faeces
^^process generally happens in macrophages and other phagocytic cells
Bile storage
Liver produces bile at a rate of 0.5 – 1 L/day (<- reprocessing takes much less energy that it would otherwise need)
Bile secreted by hepatocytes into small ducts (bile canaliculi)
Form a single duct - common hepatic duct
Bile fills the common hepatic duct
Overflow of bile enters the gallbladder
During a resting/fasting state bile is stored in the gallbladder
Bile secretion
Bile salt secretion is primarily controlled by the concentration of bile salts in the hepatic portal blood
During a meal bile salts are absorbed from the intestine, causing ↑ plasma concentration
↑ plasma concentration leads to ↑ secretion into the bile canaliculi
Secretion is greatest during and after a meal
Bile caniculus
a thin tube that collects bile secreted by hepatocytes
Hormonal control
Fat in duodenum stimulates CCK release, gall bladder contraction, relaxation of sphincter of Oddi
Secretin stimulates alkaline bile secretion from bile ducts
Neural control - parasympathetic stimulation
(during cephalic phase of digestion)
Gall bladder contraction
Relaxation of Sphincter of Oddi
Increased bile formation
Neural control - sympathetic stimulation
Relaxation of gall bladder
Reduced bile secretion
Enterohepatic circulation
synthesis and processing of BAs in the liver
down the bile duct
sphincter of odi
i’m lost
