GI Physiology 5 Flashcards
Some key functions of the liver include
Nutrient metabolism Synthesis of serum proteins Storage of nutrients Immune function Detoxification/Biotransformation
Biliary system consists of
Network of ducts that carry the hepatic secretory product (bile) to the intestine; and a bile storage site (the gallbladder)
Biliary system is critical for
Assimilation of dietary lipids
Excretion of hydrophobic compounds
Neutralization of gastric acid
Blood flow in the liver - The GI organs drain into the
portal vein
Blood flow in the liver - what percentage of blood that flows to the liver comes from the portal vein?
75%
The remaining 25% is delivered by the hepatic artery
Blood flow in the liver - from the liver, the blood drains from the ____ into ___
From the hepatic veins into the IVC
Blood flow in the liver - the portal venous system delivers blood to the liver - thus….
Contents absorbed via the GI tract have to “pass through” the liver
Portal hypertension
Inc in pressure in the portal venous system that occurs when there is dysfunction within the portal system
You will end up with pooling of blood in the GI organs
Thus - looking at GI organs can be indicator for liver dysfunction
Lobules of the liver - Blood and bile flow in same/opp directions in the liver lobules
OPPOSITE
Lobules of the liver - blood from the portal vein and hepatic artery empty into
Sinusoids - It flows toward the central vein
Lobules of the liver - Bile will flow
Away from the central vein and towards the bile duct
Describe the structure of the biliary system
Tree like
Biliary tree - a small ductal system referred to as ____ empty into the ___ ____
Canaliculi empty into the bile ductule
The canaliculi interface directly with the hepatocyte
Biliary tree The bile ductile then empties into
The bile or hepatic ducts that then drain into the common bile duct
Cells of the liver
Hepatocytes
Kupffer
Endothelial
Stellate cells
Cells of the liver - Hepatocytes
Functional cells of the liver
Polarized epithelial cells
Interface blood and bile
Cells of the liver - Kupffer
Phagocytic macrophades
Exposed to portal blood
Host defense mechanism
Cells of the liver - endothelial
Large pores between cells
Minimal basement membrane - they are not packed together tightly and have pores btw them
Cells of the liver - Stellate
In the pores of the endothelial cells
The regulate the flow of blood (or bile) to the hepatocytes
Key steps in hepatocyte biotransformation
Uptake
Transport
Biotransformation
Secretion
Key steps in hepatocyte biotransformation - Uptake
Import of compound across the basolateral membrane
Key steps in hepatocyte biotransformation - Transport
Intracellular transport (they will bind to other transports and will be carried within the cell)
Key steps in hepatocyte biotransformation - Biotransformation
Chemical modification of degredation
Key steps in hepatocyte biotransformation - Secretion
Secrete products across apical or basolateral membrane
Put it back into the blood or put it into the bile
Water soluble - into blood
Less water soluble - into bile
Key steps in hepatocyte biotransformation - Biotransformation - phase 1
Chemical rxns like oxidation, reduction, hydrolysis – You are taking the compound and adding a functional group to make them more water soluble/more polar
Key steps in hepatocyte biotransformation - Biotransformation - phase 2
Conjugation rxn
We add a large/bulky group to the molecule to make it more water soluble
Add things like Glucoronidation, Sulfation, Acetylation, Glycine Conjugation, Glutathione conjugatin
Key steps in hepatocyte biotransformation - goal of biotransformation
Take compounds and make them more water soluble
Bile acid synthesis - Bile acids and bile salts use what for synthesis
Biotransformation
Bile acid synthesis - One way is that primary bile acid (cholic acid) is first
Secreted into the bile
Goes through to bile duct and then duodenum
Primary is then converted to secondary and we inc diversity of our bile salts
Bile acid synthesis - Another way is that primary bile acid (cholic acid) can undergo
Biotransformation process (phase 1 and 2) and then we convert it to bile salt (which is more water soluble)
Bile acid synthesis - summary
From the liver, we get a mixture of bile acids and bile salts to be secreted into the duodenum
Cholesterol is used to synthesize the bile acids and bile salts along with the biotransformation process
Enterohepatic circulation of bile acids and salts - liver will secrete bile - how many grams of bile acids and salts are in the bile that is secreted compared to how many bile acids/salts we make in a day
4-6 grams
So liver makes 0.5 g of bile acid/salt a day - but 4-6 g is secreted in bile
Enterohepatic circulation allows for
Recycling of approx 90-95% of the bile acid/salt
Enterohepatic circulation - Ileum
Plays important role
Ileum expresses a Na bile salt co transporter and is the primary site for update of bile acid/salt
Enterohepatic circulation - Two important things taken up by the small intestine
Bile acids/salts and Vit B12
Regulation of bile secretion
CCK stimulates gallbladder to contract and release bile
CCK also causes relaxation of sphincter of oddi which allows passage opening of bile into intestine
Regulation of bile secreteion - key players
CCK and Ach
Somatostatin will counteract both Ach and CCK
Liver function evaluation - Hepatocyte damage
Elevation of enzymes like alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the systemic circulation
Elevated ALT and AST indicates hepatocyte damage (markers of cell death)
Liver function evaluation - Impaired protein synthesis
Dec in serum proteins in systemic circulation (albumin, clotting factors)
Indirectly can measure clotting time
Liver function evaluation - Impaired biotransformation
You will get an increase in concentration of compounds that require conjugation for elimination - like estrogen, or bilirubin
Can also get accumulations of toxins line ammonia
Liver function evaluation - Impaired bile flow (so blockage, liver is not damaged)
Inc concentration of conjugated bilirubin in the systemic circulation (leads to jaundice)
Dec bile pigments in stool (leading to gray color of it)
Dec bile secreted into the intestine (leading to fatty stool)
Hepatocytes and conjugation
We need hepatocytes to conjugate molecules
Liver function evaluation - do we have hepatocyte toxicity or do we have impaired bile flow
If there is conjugated bilirubin for example, that suggests that the liver function is good, but flow has decreased (so there is a blockage)
If it were unconjugated - then we would think liver damage
Portal hypertension is a sign of what
Liver dysfunction
High blood pressure in the portal venous system
Consequences of portal hypoertension
Varices
Splenomegaly
Ascites
Hepatic encephalopathy
