L72 Flashcards
2 normal roles of bile
- Elim wastes - bilirubin
2. Emulsify dietary fats for absorption
Bilirubin synthesis. Include steps to get it into bile
- Heme broken down
- Biliverdin -> bilirubin
Occurs in blood - Bilirubin + albumin (otherwise BR would be insoluble in blood) -> uptake into liver
- Bilirubin + glucuronic acid via UGT1A1 = water soluble for excretion in bile
What is indirect jaundice?
3 causes
Excess unconjugated bilirubin
1. Too much bilirubin made b/c of hemolysis issue
2. ↓hepatic uptake
3. Impaired intrahepatic conj
PROBLEM b/c means can’t be excreted in urine = TOXIC
What is kernicterus?
Bilirubin depositing in brain - complication of excess unconjugated BR that can’t get out of the body
What is direct jaundice?
Excess conjugated bilirubin Due to: - Impaired transport out of hepatocytes - Faulty excretion aka bile duct problem Not a huge issue b/c conj BR can be excreted into urine
What is unconj hereditary hyperbilirubinemia?
UGT1A1 defect - aka BR isn’t getting conj to glucuronic acid
Most concerned about autosomal dominant form
Are you worried about conj hereditary hyperbilirubinemia?
Not really b/c all forms are benign
If a newborn shows up with jaundice, what 3 things are you thinking of?
- Normal
- Biliary atresia - surgical emergency
- Neonatal hepatitis
What is cholestasis? 2 general categories
Bile building up in the liver
“Static bile”
Obstructive - something blocking the bile from leaving
Non-obstructive
If the cholestasis is obstructive, what is your next step in determining the etiology?
Intra vs extrahepatic block
What are lab findings to make you think an intrahepatic cause of obstructive cholestasis? Name 2 major intrahepatic diseases
↑Alk phos + BR
PBC = primary biliary cirrhosis
PSC = primary sclerosing cholangitis
Primary biliary cirrhosis (PBC)
- Cause
- Pathophys of cirrhosis
- Men or women?
- Unique lab findings
PBC - women - AMA
Idiopathic
T cells + granulomas destroy bile ducts inside the liver
AMA + = anti-mitochonridal Ab
What does PBC look like on histo?
Inflammatory cells + granuloma gradually compress the bile duct out of existence
Primary sclerosing cholangitis (PSC)
- Pathophys
- Associated diseases
- Male vs women
- Increased risk of what disease
Cause unknown Intra and/or extrahepatic bile duct damage due to - Inflam - Obliterative fibrosis **Associated with CHRON's + UC** ↑risk cholangiocarcinoma
PSC histo
Onion skin fibrosis around bile duct
Skip pattern
- Might miss on biopsy
- MRI better dx
Secondary biliary cirrhosis
- Aka cirrhosis is secondary to something else… what?
- Intra or extra hepatic bile duct block
- How will entire liver look?
INTRAhepatic Secondary to: - Tumors - Bile stones - Pancreatitis Liver is GREEN
Secondary biliary cirrhosis on histo
Large, irregular islands of fibrosis
- *Bile ductules
- Liver is tring to make new ducts but don’t work
- Non-fxnal but used for dx
What test would you order if you suspect:
PBC
PSC
Obstruction as cause for biliary block
PBC - AMA
PSC + obstruction = cholangiogram
Acute hepatitis histo
Lobular disarray
- Liver looks disorganized b/c cells have been lost and regenerated irregularly
Injury markers:
- Ballooning -> apoptosis -> bridging necrosis
IF see inflam cells - makes you think viral cause
What is the difference between toxic liver injury due to intrinsic vs idiosyncratic hepatotoxins?
Intrinsic = toxins that if you give a big enough dose will damage anyone's liver (acetaminophen, alcohol) Idiosyncratic = causes injury only in rare cases
Which zone sees necrosis in acetaminophen injury?
Zone 3 = closest to central vein (furthest from O2 supply)
Disorders in blood flow can damage the liver. 3 classifications of vascular disorders leading to hepatitis - examples of each
Where is the impaired flow:
- Prehepatic
- Thrombosis - Intrahepatic
- Cirrhosis - Post-hepatic aka hepatic venous outflow
- Budd Chiari
Does the liver usually infarct if the inflow is impaired?
NO B/c dual vasc blood supply - Hepatic artery - Portal vein EXCEPT transplant pts
Remember, what is Budd Chiari?
IVC or portal vein thrombosis
