Liver Physiology Bile and Jaundice Flashcards
What are the functions of the liver?
Removal and detoxification and first pass metabolism of orally administered drugs
Storage
Synthesis eg. albumin, bile, transport proteins
What is the role of the Portal Vein?
Drains GIT from the lower esophagus to the rectum
What does capillary bed 1 do?
Drains contents from small intestine
Where is capillary bed two found?
Within the liver
What is the structural unit of the liver called?
The hepatic lobule
What three ducts make up the triad found on each apices?
hepatic portal vein, hepatic artery and the bile duct
How do we know it’s the bile duct in a histology image?
small lumen, presence of epithelium cells line duct systems
What are the white spaces in-between pink cells?
Hepatic sinusoids
What types of cells are found in the liver?
Hepatocytes
Reticuloendothelial cells - structure
Endothelial cells
Hepatic stellate cells
cholangiocytes - bile secretion and motility
What is the function of the hepatic lobule?
Drains blood from portal vein and hepatic artery to hepatic/central vein
What is the function of the portal lobule?
Drains bile from hepatocytes to the bile duct
What is the function of the Hepatic Acinus?
Supplies oxygenated blood to hepatocytes
What Zone is the most oxygenated and what zone is the least oxygenated
Zone 1 = most oxygenated
Zone 3 = least oxygenated
What are the functions of zone 1?
Gluconeogenesis
Oxidation of fatty acids
What are the functions of zone 3?
Glycolysis
Lipogenesis
P450 enzyme mediated detoxification
What causes portal vein oxygenation to decrease?
Increasing GIT activity and O2 demand
What does zone 1 create?
Local microenviroments/
What happens when we move further away from the shirt axis?
Nutrients start to deplete
Where is bile produced and stored?
Produced in the liver
Stored in the gall bladder
What are the functions of bile?
Emulsification of lipids
Hormonal action
Elimination of waste products eg. bilirubin
What are the main components of bile?
Water, bile acids, HCO3-, Bilirubin
What synthesizes bile acids?
Hepatocytes
What is the aqueous component contributed by?
Bile duct epithelial cells (cholangeocytes)
What stimulates duct cells?
Secretin but does not affect bile salt synthesis
What are examples of primary bile acids?
Cholic acid
Chenodeoxycholic acid
Synthesized by hepatocytes from cholesterol
What are examples of secondary bile acids?
Deoxycholic acid
Lithocholic acid
Generated by de-hydroxylation of bile acids by intestinal bacteria
How are conjugated bile acids formed?
Addition of glycine or taurine groups to primary or secondary acids in the liver
How is conjugation beneficial?
Helps solubility of acids for emulsifying lipids
How are lipids emulsified by bile?
Hydrophobic side of bile acid binds to lipid
Hydrophilic side has polar regions - lipid can’t reform - allows lipases to come in and aggregate lipid
Surface area for digestion increased
Fat droplets coated with bile salts are suspended in water
What is urso-deoxycholic acid?
Bile acid used to treat liver and neurodegenerative disease
Inhibit apoptosis
Abundant in bear bile - only produced in small amounts in human colon
What bile acid can act as a signaling molecule?
GPBA
control peristalsis, energy homeostasis and anti-inflammatory
How does bile enter the duodenum?
Via the sphincter of Oddi
Common exit with pancreatic secretions - allows for mixing
How are bile acids returned to the hepatocytes?
Via sodium dependent organic anion transporter
What does conjugation do to bile acids in the entero-hepatic recirculation?
Increases water solubility of bile salts - renders them relatively impermeable to the duodenum
Accumulate in the lumen
Where are bile acids reabsorbed?
In the terminal ileum
What is the function of the gall bladder?
Storage and concentration of bile
Contract to release bile when required
What are the three phases of for the gall bladder?
Cephalic, gastric and intestinal phase
What is the cephalic phase triggered by?
Thought and taste -> GB emptying
What is the gastric phase triggered by?
vagus stimulated by gastric distension -> GB emptying
What is the intestinal phase stimulated by?
Presence of acid in the duodenum -> secretin & ductal epithelial cells produce bicarb rich secretion
Presence of fat in the duodenum -> CCK & stimulation of contraction of GB
How are gall stones formed?
Disregulation or an imbalance of cholesterol, phospholipids and bile salts in bile
What are the consequences of removing your gall bladder?
Bile won’t be as concentrated
Bile is more dilute - less effective at absorbing lipids
How is bilirubin removed?
Conjugated to glucuronic acid in the liver
Enters biliary system in bile
Enters small intestine where bacterial proteases turn it into urobilinogen
Mostly emoved as faeces or enters portal vein
Goes back into the blood and is excreted in urine via kidneys
What is bilirubin?
A breakdown product of heme from red blood cells
What is jaundice?
Elevated unconjugated bilirubin in the blood
How does jaundice occur?
High levels of Heme breakdown or incomplete conjugation