Liver Path- Nelson Flashcards
Define jaundice
Yellow discoloration of the skin due to retention of bilirubin
Defice icterus
Yellow discoloration of the sclera due to retention of billirubin
*earliest sign of jaundice
Define cholestasis
Impaired secretion of bile
What cells are responsible for taking RBCs out of circulation to break them down? Then what happens?
Reticuloendothelial cells (macrophages)
Many located in spleen
Break down hemoglobin into: heme + globin
Globin = protein, so broken down to amino acids
Heme = broken down into Fe and protoporphyrin
Fe = recycled
Protoporphyrin is converted to unconjugated bilirubin
What protein transports bilirubin to the liver?
Albumin
What gets conjugated to bilirubin in the liver?
Glucuronic Acid
*makes CONJUGATED BILIRUBIN
What enzyme is responsible for conjugating bilirubin?
UDP-glucuronyl-transferase
Is unconjugated bilirubin able to be excreted in the urine?
NO!!!! it is water INSOLBULE so it cannot get excreted
It is bound to albumin
Toxic to tissues
How is conjugated bilirubin excreted? Is it soluble?
It is SOLUBLE
-Conjugated in hepatocytes
- Canicular transport protein transfers it to bile caniculi
- Goes into bile ducts, and released into duodenum
- Intestinal flora convert it to urobilinogen
- 80% is excreted in feces = WHY YOUR POOP IS BROWN!!
How much total serum bilirubin is needed to produce jaundice?
2-3 mg/dL
Which form of bilirubin is toxic to tissues?
Unconjugated bilirubin
Potential causes of unconjugated hyperbilirubinemia?
- Extravascular hemolysis
- Jaundice of newborn
- Gilbert Syndrome
- Crigler-Najjar Syndrome
Potential causes of conjugated hyperbilirubinemia?
- Dubin-Johnson Syndrome
- Obstructive jaundice
What would cause an increase in BOTH conjugated and unconjugated bilirubin?
Viral hepatitis!
Inflammation disrupts hepatocytes and small bile ductules
Why do newborns sometimes get jaundice?
Newborn liver has transiently low UGT activity
Leads to high unconjugated bilirubin
What is a severe complication of jaundice in a neonate?
UCB is fat soluble and can deposit in the basal ganglia = KERNICTERUS
Leads to neurological damage and death
What is treatment for neonatal jaundice?
Phototherapy
Does phototherapy conjugate bilirubin???
NO!!!!!!!!!!!!!!!!!!!!
It transforms unconjugated bilirubin to a water soluble form so it can be excreted in the urine….. BUT IT DOES NOT CONJUGATE IT!
What is Gilbert’s Syndrome?
Mildly low UGT activity
Leads to increased unconjugated bilirubin (
What is Crigler-Najjar Syndrome?
ABSENCE of UGT in fetus
Leads to increased unconjugated bilirubin
Kernicterus = usually fatal
What is Dubin-Johnson Syndrome?
Deficiency of bilirubin canalicular transport protein
Increased CONJUGATED bilirubin
Liver is DARK, otherwise not clinically significant
What syndrome produces a DARK LIVER and no other clinically significant consequences?
Dubin-Johnson Syndrome = deficiency of bilirubin canalicular transport protein
Morphological findings in hepatocellular cholestasis
- Bile with-in hepatocytes
- Canalicular bile stasis
- Feathery degeneration of hepatocytes
What is ascending cholangitis?
Secondary bacterial infection of the biliary tree due to extrahepatic biliary obstruction
Morphologic findings in canalicular cholestasis?
- Canaicular bile stasis
- Feathery hepatocytes
- Bile with-in distended bile ducts
- Bile duct proliferation with in portal tracts
Which 2 hepatitis viruses are transmitted fecal-oral?
Hep A
Hep E
The vowels hit your bowels
What does carrier state mean in regards to hepatitis?
Persistent hepatitis infection without significant ongoing necroinflammatory disease
Typically occurs as a result of exposure at childbirth (perinatal transmission)
What hepatitis virus must be encapsulated by HBV to be infective?
Hep D
-defective ssRNA virus
Difference between superinfection and coinfection?
Superinfection = HDV infects individual with chronic HBV infection
Co-infection= Hep D is transmitted simultaneously with Hep B (infected at same time)
Which is worse, superinfection or coinfection?
Superinfection!
What causes hepatocellular injury in hepatitis infeciton?
Patient’s cellular immune response
CD8+ T cells
Subsequent lysis of infected cells
Which hepatitis viruses can cause chronic disease?
Hep B
Hep C
Hep D (with Hep B infection)
consonants can cause chronic hepatitis!
What viruses can cause viral hepatitis?
Hepatitis Viruses (A, B, C, D, E)
EBV
CMV
When is acute viral hepatitis defined as chronic viral hepatitis
When symptoms last > 6 months
Jaundice Dark urine Fever Malaise Nausea Elevated liver enzymes ALT>AST
What do you think it is?
Acute Hepatitis!
Jaundice- increased CB and UCB!
Dark urine- increased CB
Is acute viral hepatitis frequently biopsied?
Nope!
Pathological findings associated with acute viral hepatitis?
Lobular hepatits:
- Diffuse liver cell degeneration w/ necrosis & apoptosis
- Kupffer cell hyperplasia
- Mononuclear (predominately lymphocytes) with in portal tracts and lobules
Why is it sometimes necessary to perform a liver biopsy in chronic viral hepatitis?
Often required for assessing the degree of liver damage
-clinical findings of chronic viral hepatitis are highly variable
Pathologic findings in chronic viral hepatitis?
Periportal hepatits with piecemeal necrosis
Bridging necrosis
Progressive fibrosis leading cirrhosis
What pathologic clue can be seen on liver biopsy that would suggest chronic HBV infection?
Ground glass hepatocytes
Do patients with acute massive hepatic necrosis always get cirrhosis?
Nope!
Clinically suffer acute liver failure- acute toxic agent causes no fibrosis
Reticulin framework is intact, liver can regenerate without much architectural distortion
How is perinatal HBV prevented?
Treat with Hep B immune globulin (HBIG) and Hep B vaccine 2-12 hours after birth
85-95% effective in preventing development of HBB chronic carrier state
Define autoimmune hepatitis
Liver injury due to a T-cell mediated autoimmune pathogenesis
Treatment for autoimmune hepatitis?
Immunosuppressive agents (steroids)
Define cirrhosis
End stage liver damage characterized by disruption of the normal hepatic parenchyma by bands of fibrous and regenerative nodules of hepatocytes.
Most common cause of cirrhosis?
Alcoholic liver disease (60-70%)
3 complications associated with cirrhosis?
Hepatic Failure
Portal Hypertension
Hepatocellular carcinoma
Most common cause of acute liver failure?
Acetaminophen overdose (50% of cases)
Most common cause of chronic liver failure?
Chronic liver disease associated with cirrhosis
Who gets reye’s syndrome?
Children and teenagers following a viral infection that was treated with aspirin
What is reye’s syndrome?
Rare, often fatal childhood hepatic encephalopathy
What is found on liver biopsy for Reye’s syndrome?
Microvesicular steatosis
Widespread mitochondrial injury
Most common cause of portal hypertension?
Liver cirrhosis
Four main complications of portal hypertension
- Ascites
- Portosystemic shunts (anastamoses- esophageal varices)
- Splenomegaly (congestive)
- Hepatic Encephalopathy
Complication of portal vein thrombosis?
Portal hypertension
But as obstruction is often before the liver, ascites does not typically occur
Which two Hepatitis viruses are non-enveloped?
A and E
