Liver Flashcards
How do you distinguish between conjugated bilirubinemia and unconjugated bilirubinemia (a test)? What is the differential diagnosis for unconjugated bilirubinemia?
Conjugated bilirubinemia will end up in the urine, and you can test that shit.
DDx: Newborn (esp. if there is hemolytic dz of the newborn –> hemolysis + limited conjugation ability), Crigler-Najjar, Gilbert, hemolysis
Does direct bilirubin measure conjugated, or unconjugated bilirubin?
Conjugated
Regarding labs, how can you distinguish between the two major forms of conjugated bilirubinemia: cholestatic jaundice and hepatocellular jaundice?
In cholestatic jaundice, ALT and AST are only mildly elevated while ALKPhos is markedly elevated (>3x upper normal limit).
In hepatocellular jaundice, ALT and AST will be super high (>300 IU) while the ALKPhos will be <3x upper limit of normal
What diagnostic tests are good to distinguish between intrahepatic and extrahepatic cholestasis?
Ultrasound or CT helps you visualize dilated ducts. If they are dilated = extrahepatic obstruction
Hepatocytes in zone ___ of the liver acinus are most susceptible to ischemia.
zone 3
What is the specific mechanism by which rifampin can cause bilirubinemia? What type of bilirubinemia is it (conjugated vs. unconjugated)?
Inhibition of OATP-2, which aids in uptake of UCB by hepatocytes. It leads to unconjugated bilirubinemia.
How does Gilbert syndrome present? What is the pathophysiology behind this disease? What is the treatment?
Presents with jaundice/bilirubinemia during times of stress (lack of sleep, starvation, etc.). It is unconjugated because the defect is in the glucuronosyl transferase enzyme (low activity). No treatment; bouts of jaundice are self-limited.
What specific transporter in the liver is particularly sensitive to stress (ie. infection, drugs), which can potentially lead to bilirubinemia and bilirubinuria? What is its function?
MRP-2 transporter - transports conjugated bili into bile canaliculi
Which cell type in the liver mediates the fibrosis that is characteristic of cirrhosis?
stellate cells
Describe the pathogenesis of ascites.
Increased pressure in the sinusoids -> lymphatics on the surface of the liver dilate and weep fluid into the peritoneal cavity.
Hypertension of the portal system at which of the following locations is likely to lead to splenomegaly and hypersplenism: pre-hepatic, intrahepatic, post-hepatic?
Intrahepatic and pre-hepatic hypertension typically cause marked splenomegaly and hypersplenism
What are the mechanisms by which one could get unconjugated hyperbilirubinemia?
- Hemolysis
- Impaired delivery (ex. right heart failure)
- Impaired uptake (OATP-2)
- Impaired storage in hepatocytes
- UDP transferase gets messed up (Gilbert, Crigler-Najjar)
What is the genetic defect that causes Gilbert syndrome?
Mutation of UGT1A1 gene on chromosome 2
What are cholesterol stones made out of?
Cholesterol
What are mixed pigment and black pigment stones made out of?
Black pigment stones are made out of unconjugated bilirubin and calcium and mixed stones are made out of bilirubin, calcium, and cholesterol
What causes biliary colic?
Blockage of the cystic duct by a stone.
What is a drug that you can use to treat gallstones and cholestasis? How does it work?
Ursodiol/ursodeoxycholic acid - decreases rate of cholesterol absorption
Why does acute hepatitis cause an elevation of serum B12 and iron?
When hepatocytes die, they release B12 and ferritin
What is the treatment for acetaminophen toxicity and how does it work?
Acetylcysteine replenishes reduced glutathione so toxic NAPQI can be converted to a water soluble metabolite for excretion
What are the risk factors of NAFLD?
Female, fat, forty, fertile
What is the treatment for early hepatorenal syndrome?
Plasma volume expansion w/ albumin
What is the treatment for late hepatorenal syndrome?
Vasopressors like octreotide, midodrine. Albumin helps restore effective arterial blood volume.
Liver and biliary tree disorders can sometimes refer pain to the _______.
Shoulder
Which cell type in the liver do FFAs cause damage to? What is the mechanism by which fibrosis occurs in this case?
FFAs –> oxidation products –> Kuppfer cells make TNF-a –> Stellate cells make collagen
What is the carrier protein for unconjugated bilirubin?
albumin
What is the rate-limiting step of bilirubin metabolism?
Uptake of unconjugated bilirubin into hepatocytes
Which step in bilirubin metabolism is most resistant to dysfunction?
conjugation
What are the essential factors for gallstone formation?
- Saturation (thermodynamics)
- Stasis
- Nucleation (kinetics)
What enzyme is responsible for unconjugating bilirubin after it has been secreted into the bile ducts?
Ductal epithelial cells express beta-glucuronidase
Explain why INR can be elevated without hypoalbuminemia in the setting of hepatitis.
The half life of clotting factors is shorter than albumin, so there will be a time when clotting factors are low while there is still plenty of albumin
Right-sided heart failure may cause necrosis of zone ____ hepatocytes.
3
Describe the pathogenesis of hepatorenal syndrome.
Cirrhosis -> increased portal venous pressure, liver endothelial cells make vasoconstrictors and have increased sensitivity to vasoconstrictors, and they also make less NO
Splanchnic circulation increases NO production to increase flow, which leaks out into into the systemic circulation -> low BP -> increased cardiac output
The splanchnic vessels act as a third space and keep the EABV low
Low BP triggers the RAAS and SNS systems –> epinephrine and a lot of angiotensin II constricts both afferent and efferent arterioles in the kidneys -> kidney failure
Is a stone in the cystic duct likely to cause bilirubinemia?
No, conjubated bilirubin can still get down the common bile duct
What are the mechanisms by which a severe GI bleed in a cirrhotic patient can cause oliguria?
Low BP -> RAAS activation and concentration of urine
If the patient has cirrhosis already, this can precipitate hepatorenal syndrome -> kidney failure
What are the mechanisms by which a severe GI bleed in a cirrhotic patient can cause somnolence?
Hypoperfusion from blood loss
Blood in the GI tract liberates ammonia and is absorbed, then bypasses the liver from portosystemic shunts and goes to the brain (hepatic encephalopathy)
