Gastrointestinal Tract 5 - Liver and Biliary System Flashcards
Liver is the largest internal organ?
True
The liver contains how many lobes ? What kind of overall strucure does the liver have?
4 different lobes, hepatic lobule structure
Hepatic Lobule Structure
- Hexagonal structure with
- Central vein running through the centre
- Portal triads at each corner
Each of the royal triads is composed of:
- Hepatic artery
- Portal vein
- Bile duct
Cell types in the liver
1) Epithelial Cells
- Hepatocytes: ~70% of the cells in the liver
- Bile duct epithelium or cholangiocytes: 3-5%
2) Kupffer cells-macrophages
3) Endothelial cells-lining the sinusoids-”fenestrated”
Exocrine gland in the liver forms
Forms and secrets bile
Liver functions
Metabolism and storage of nutrients
- Liver matches supply to demand (e.g., storage of glucose as glycogen)
Deactivation and detoxification
- Drugs, hormones, waste products, toxicants
Production of circulating proteins
- e.g., blood coagulation factors, lipoproteins
Constituents of bile
- Bile acids-synthesized within the hepatocyte from cholesterol-amphipathic
- Cholesterol (slightly amphipathic)
- Salts (e.g., Na+, K+, and HCO3-) and water
- Phospholipids e.g., phosphatidyl choline-amphipathic
- Bile pigments e.g., bilirubin
- Trace metals
Pancreatic lipase is a water soluble enzyme and can only work at the surface of lipid droplets,
Therefore
Large lipid droplets need to be made smaller for efficient access by lipase
Emulsification
Making large droplets of fat into smaller ones so lipase can have access
Emulsification requires
- Mechanical disruption to make lipid droplets smaller (GI motility)
- Emulsifying agent to prevent droplets from re-aggregating
- Amphipathic bile acids
- Phospholipids
Bile acids also form “mixed micelles” with
phospholipids and products of lipase digestion (free fatty acids and monoglycerides)
“micelle” is a soluble cluster of
amphipathic molecules with nonpolar groups in the middle and polar groups on the outer layer
Micelle function
- Micelles keep monoglycerides and fatty acids in small soluble aggregates
- Equilibrium between the micelle and free fatty acid and monoglycerides
- Free forms diffuse across the small intestine epithelium
- Micelles are like a “holding station” for small nonsoluble lipids
Which cells produce bile acids?
Hepatocytes
The formation of bile is done by:
- hepatocytes: produce bile acids, phospholipids, cholosterol, and bile pigments (into bile canaliculi), via active transport
- bile duct: add HCO3 and H2O to bile.
- gall bladder: stores and concentrates bile
b/w meals the expels it into duodenum after.
Enterohepatic circulation of bile acids
- 20-40 g of bile acids are released into the intestine each day ~ 0.5 g is lost in the feces (95% recovered).
- This recycles the bile acid.
What does the enterohepatic circulation of bile acids allow?
Allows the secretion rate to greatly exceed the synthesis rate.
Steps for bile acid recycling
- Bile acids are released by the liver/gall bladder into the duodenum for fat digestion
- Bile acids are reabsorbed across the small intestine (ileum) into the portal circulation
- Bile acids are transported back into hepatocytes
What causes bile acids to be lost in feces?
Dietary fibre sequesters bile acids preventing them from cycling back to the liver and resulting in their loss in feces
- More bile acids are then synthesized from cholesterol
- Lowers plasma cholesterol
Can drugs undergo enterohepatic circulation, and if so which ones?
- Can be beneficial (e.g.,loperamide)
- Can be a disadvantage (reducing bioavailability)
What’s regulates hepatobiliary secretion during intestinal phase? And how
- Secretin
Or
- cholecystokinin (chole “bile”, cysto “bladder”, kinin “to move”
Where and how is secretin produced?
Secretin is produced and released by S-cells in the duodenum
(Stimulated by acid in the duodenum)
How does secretin regulate hepatobiliary secretion during intestinal phase?
Secretin increases HCO3- secretion by the bile duct cells (and the pancreas)
How does cholecystokinin regulate hepatobiliary secretion during intestinal phase?
CCK increases contraction of the gall bladder and relaxes the sphincter of Oddi.
- bile is released into the duodenum
Where and how is cholecystokinin produced?
Produced by the I cells in the duodenum and jejenum
- Stimulated by digested fats/proteins in upper small intestine
Two types of gallstones
- cholesterol stones (majority)
- pigment stones (less common)
Cholesterol is water insoluble and only kept in solution in
bile through the formation of micelles with bile acids and phospholipids
If the concentration of cholesterol in bile becomes high relative to bile acids, cholesterol starts to
precipitate out , “nucleating” agent also required (e.g., protein, bacteria)
Pigment stones
Caused by excessive hemolysis (red blood cell breakdown) which increases bile pigment concentration in bile, pigments form precipitates with Ca2+
Gallstones consequences
- Depends on location of stones; may cause obstruction/infection of gall bladder, liver, pancreas
- Pain, nausea, jaundice, malabsorption of fats and fat soluble vitamins
Treatment for gallstones?
- Cholecystectomy (removal of gallbladder)
- Need to reduce fat in diet
- Removal of stones
- Drugs to dissolve gallstones
