62 - GI Liver and Gallbladder Flashcards
Describe the directional flow of blood and bile through the liver
- Liver is divided into left and right lobes
- Each lobe is divided into lobules
- Lobules are arranged as stacks/plates of cells (primarily hepatocytes)
- At the “corner” of each lobule there is a bile duct, hepatic artery and portal vein known as the “portal triad”
- In the center of the lobule is the hepatic (central) vein
- Blood flows from the hepatic artery and portal vein to the hepatic vein while bile flows away from the hepatic vein toward the bile duct
How does intestinal blood relate to this blood flow?
Intestines dump into portal vein which goes to the liver, out comes the hepatic vein that drains into vena cava – 70% of blood to the liver is from the portal vein. The liver is a FILTER for things that you take into your system
What is the role of hepatocytes?
Hepatocytes act as filters
What are the steps in biotransformation in the hepatocytes (think transformation of drugs that enter the body by the liver)
- Uptake across basolateral membrane
- Intracellular transport
- Biotransformation (chemical modification and degradation)
- Secretion across apical or basolateral membrane into blood or bile
How does uptake occur?
Uptake can occur via diffusion or protein transport
What are the two phases of biotransformation?
Phase I = molecular modification
Phase II = Conjugation
What is the overall goal of biotransformation?
To make molecules more water soluble
What does phase I accomplish?
Molecular modification
- This exposes a functional group via oxidation, reduction or hydrolysis
What does phase II accomplish?
Conjugation
- This is accomplished by using the exposed group from phase I in order to make the molecule more water soluble by glucoronidation, sulfation and acetylation
What is the bile salt biosynthetic pathway
From start to finish…
- Cholesterol
- Bile acid
- Bile salt
- Duodenum
The most common bile acid is CHOLIC ACID (know this)
What is the difference between primary and secondary bile acids?
Primary
- Primary bile acids are secreted by the liver
Secondary
- Secondary are modified and secreted into the duodenum, go through the GI tract and are modified by intestinal flora
- Secondary bile acids are the ones that bacteria change the chemical structure of
Where is bile stored and concentrated?
The gallbladder
How much bile is synthesized and secreted each day? What accounts for this?
Secretion
- 12-36 grams of bile salt secretion per day
Synthesized new
- Only 600 mg synthesized each day
Reasoning
The newly synthesized amount is the amount is lost in feces daily
- The rest is recycled after it goes through the GI tract
- The enterohepatic circulation is the recycling system
- 95% gets reabsorbed in the ileum
What is the key stimuli to promote the secretion of bile into the duodenum?
Primary simulus
- CCK (cholicystokinin)
- CCK induces gallbladder contraction and releases bile by relaxation of the sphincter of Oddi
- This allows the ampulla to empty its cotents into the major duodenal papilla
Another stimulus
- Acetylcholine
- Not the main one, but plays a significant role
What is the key stimuli to inhibit the secretion of bile into the duodenum?
Primary inhibitor
- Somatostatin is the key negative regulator of gallbladder secretion of bile
What role does the enterohepatic circulation play in this process?
Reabsorbs 95% of bile from the GI tract for recycling and reuse
Pathophysiology of jaundice
- Jaundice is a condition of hepatocellular failure that is characterized by a yellowing of the skin due to elevated blood levels of bilirubin
- Bilirubin is a product of heme metabolism following lysis of red blood cells in the liver
- Impaired hepatic excretion of bilirubin causes an accumulation of bilirubin in the blood
What does jaundice indicate?
Jaundice is therefore a clinical indicator of hepatic dysfunction
What are the two types of jaundice?
- Hemolytic
- Obstructive
Describe hemolytic jaundice
Hemolytic jaundice (HJ) is simply caused by excessive breakdown of red blood cells
Describe obstructive jaundice
Two types
- Extrahepatic obstructive jaundice (EOJ) is caused by an obstruction, such as in the bile duct, which impedes bilirubin excretion outside the liver
- Intrahepatic obstructive jaundice (IOJ) is caused by an obstruction in the liver, such as impaired hepatocyte function or blocked bile caniculi
What is portal hypertension?
- Portal hypertension is defined as high blood pressure in the portal venous system
What causes portal hypertension?
The causes of portal hypertension are disorders that impede blood flow through the liver or vena cava
What does long term portal hypertension lead to?
1 - varices: distension of collateral veins in the esophagus, rectum, and stomach.
2 - splenomegaly: enlarged spleen
3 - ascites: accumulation of fluid in the peritoneal cavity
4 - hepatic encephalopathy: accumulation of toxins resulting in cell death in the central nervous system
