Nelson: Liver Flashcards
What is jaundice?
Yellow discoloration of the SKIN d/t retention of bilirubin
When is jaundice clinically evident?
as total serum bilirubin approaches 2-3 mg/dl
What is icterus?
yellow discoloration of the SCLERA d/t retention of bilirubin
What is cholestasis?
impaired secretion of BILE
What are the steps involved in bilirubin metabolism?
Reticuloendothelial cells convert heme (brkdown of old RBC, hepatic heme, marrow RBC precursors) to bilirubin>
bilirubin is transported to the liver complexed w/ ALBUMIN (unconjugated bilirubin)>
cbilirubin is conjugated w/ glucuronic acid in liver cells (conjugated bilirubin)>
conjugated bilirubin is excreted in BILE (brown stools)
What form of bilirubin is toxic to tissues?
Unconjugated (indirect)
- water soluble
- bound to albumin
- not excreted in the urine
Which form of bilirubin is water soluble, not toxic to tissues and is excreted in the urine when present at high serum levels?
conjugated bilirubin
What are some of the causes of unconjugated bilirubinemia?
- Increased bilirubin production
- impaired hepatic bilirubin uptake
- impaired bilirubin conjugation
What increases bilirubin production?
- Extravascular hemolysis
- Extravastation of blood into tissues
- Intravascular hemolysis
- Dyserythropoiesis
What impairs hepatic bilirubin uptake?
- Heart failure
- Portosystemic shunts
- Gilbert’s syndrome
- Drugs
What impairs bilirubin conjugation?
- Crigler-Najjar syndrome (I or II)
- Gilbert’s syndrome
- Neonatal jaundice
- Hyperthyroidism
- Ethyinyl estradiol
- Liver disease
What causes conjugated hyperbilirubinemia?
- extrahepatic cholestasis (biliary obstruction)
2. interhepatic cholestasis
What causes biliary obstruction?
- Choledocholithiasis
- Tumors
- PSC
- AIDS
- Pancreatitis
- Strictures
- Parasitic infxns
What causes intrahepatic cholestasis?
- Hepatitis (many types)
- Drugs & toxins
- Primary biliary cirrhosis
- Sepsis & hypoperfusion
- Infiltrative diseases
- Total parenteral nutrition
- Following organ transplant
- Hepatic crisis in sickle cell
- Pregnancy
- End-stage liver disease
What causes normal neonatal alterations in bilirubin metabolism?
- Increased bilirubin production (neonates have relatively more RBCs with a shorter life span)
- Decreased bilirubin clearance (due to physiologic decrease in UGT1A1 activity)
- Increased enterohepatic circulation*
What are pathological causes of unconjugated hyperbilirubinemia?
- Immune-mediated hemolysis (ABO or Rh(D) incompatibility)
- Inherited RBC membrane or enzyme defect
- Sepsis
- Inherited defects in UGT1A1 activity (e.g. Crigler-Najjar syndrome, Gilbert’s syndrome)
- Breast milk jaundice*
- Intestinal obstruction*
- Breastfeeding failure jaundice*
What are normal TB levels in almost all term and near term newborn inftants?
> 1 mg
If an infant has mild unconjugated hyperbilirubinemia w/ peak TB what can you expect the levels to be?
— 7 to 9 mg/dl in Caucasian & AA infants
— 10 to 14 mg/dl in Asian infanats
A TB >25-30 mg/dl in an infant is indicative of….
How do you treat it?
severe hyperbilirubinemia
Phototherapy
How does severe hyperbilirubinemia affect other organ systems?
- Bilirubin-induced neurologic dysfunction (BIND)
- Acute bilirubin encephalopathy (ABE)
- Long-term neurologic sequelae or kernicterus (if inadequately tx)
What is Gilbert’s syndrome?
AR, BENIGN disorder
What causes Gilbert’s syndrome?
decreased GTF activity (UGT1A1 is 30% of normal)
What lab findings are associated w/ gilbert’s sndrome?
increased unconjugated bilirubin
Morphological findings show:
bile w/in hepatocytes
canalicular bile stasis
feathery degeneration of hepatocytes
intrahepatic cholestasis
Morphological findings show: Canalicular bile stasis Feathery degeneration of hepatocytes Bile lakes Bile w/in distended bile ducts PORTAL TRACT EDEMA Bile duct proliferation w/in portal tracts
Extrahepatic cholestasis
What is acute cholangitis? What is seen morphologically?
secondary bacterial infection of the biliary tree
Extrahepatic biliary obstruction → ascending cholangitis
What is chronic passive congestion?
centrilobular congestion
WHat is centrilobular hemorrhagic necrosis?
centrilobular congestion w/ cenrilobular necrosis
What is cardiac sclerosis?
fibrosing rxn following long standing CPC and or centrilobular necrosis
Pathology–centrilobular fibrosis
What are the common causes of CPC, CHN and CS?
RHF, LHF, shock, hepatic vein thrombosis>
congestion and hypoperfusion> centrilobular necrosis
What is a hepatic infarct?
rare
secondary to double blood supply
What is a hepatic infarct often caused by?
vasculitis, embolism, or tumor
What is hepatic vein thrombosis (bud chiari syndrome)?
thrombosis of 2+ hepatic vein branches
What is the classical clinical triad for HVT?
hepatomegaly
ascites
abd pain
What often causes HVT?
conditions htat make clotting more likely
May also have a thrombosis in the IVC
How do you dx HVT?
imaging of thrombi
What si the pathology of HVT?
centrilobular hemorrhagic necrosis
cardiac sclerosis
What is sinusoidal obstruction syndrome?
presence of obstructive, non-thrombotic lesions of small hepatic veins in pts exposed to radiation &/or hepatoxins
What is the pathogenesis of sinusoidal obstruction syndrome?
toxic damage to hepatic sinusoidal endothelium, secondary to cytoreductive agents (e.g. chemotherapy)> MARKED NARROWING/OBLITERATION OF CENTRAL VEIN lumens by SUBENDOTHELIAL SWELLING AND FIBROSIS
What is the acute form of sinusoidal obstruction syndrome associated with?
painful hepatomegaly
sudden wt gain
increased serum bilirubin
What is the chronic form of sinusoidal obstruction syndrome associated with?
Toxic effects of pyrrolizidine alkaloids found in certain herbal teas
sx of budd chiari
How do you dx sinusoidal obstruction syndrome?
clinical features
imaging
liver biopsy (chronic form)
What complications are associated wtih portal vein thrombosis?
portal HTN (no ascites b/c obstruction is presinusoidal)
What are extrahepatic causes of portal htn?
- Intraabdominal sepsis
- hypercoaguable disorders
- trauma
- pancreatitis or pancreatic cancer
What are intrahepatic causes of PVT?
- cirrhosis
2. invasion of portal vein by hepatocellular carcinoma
What is Peliosis Hepatis?
primary hepatic sinusoidal dilation w/ sinusoidal rupture> blood filled spaces
typically resolves after correction of underlying disorder
How is hepatitis A transmitted?
Fecal- oral (contaminated food & water)
How does Hepatits A cause infection?
Incubates 2-6 wks>
Virus infects liver cells → hepatocellular injury d/t CD8+ T-cell & lysis of infected hepatocytes
How does HAV usually present?
majority are asymptomatic
some present w/ acute hepatitis
does NOT cause chronic hepatitis
How is HBV transmitted?
Parenteral, Sexual/close contact, perinatal
Blood & body fluids (saliva, semen, vaginal secretions)
How does HBV cause infection?
Incubation period = 4-26 wks
Virus infects liver cells → hepatocellular injury d/t CD8+ T-cell & lysis of infected hepatocytes
What percent of HBV pts are asymptomatic? acute? chronic?
Majority (70%) of pts asymptomatic
Some (30%) clinical acute hepatitis
90% of infections resolve
5% develop chronic hepatitis
(1) → Non-progressive disease
(2) → Progressive disease→ cirrhosis
(3) → Hepatocellular carcinoma
(4) → Asymptomatic carrier state (esp. if exposed as young
How is HCV transmitted?
Parenterally (blood, IV drug use), Sexual/close contact, rarely perinatally
What percent of pts develop chronic HCV?
20% develop acute hepatitis
80% develop chronic hepatitis
• 20-30% → cirrhosis
• Most pts asymptomatic
What is the MCC of chronic liver disease in the US?
HCV
Genotype 1a
How is HDV transmitted?
Individual w/ chronic HBV (superinfection)
Transmitted simultaneously w/ HBV (coinfection)
What does HVC need in order to replicate?
Only able to replicate in presence of HBV, encapsulated by HBsAg
How does an infection w/ HBV and HDV compare to one w/ HBV alone?
MORE SEVERE
• Increased mortality from acute hepatitis
• Increased progression to chronic hepatitis (superinfection form only)
What populations is HDV commonly found in?
See in IV drug users or certain geographical locations (Brazil, Africa, Middle East, S. Italy)
Can you distinguish and acute coinfection of HBV and HDV from HBV?
No
transiet & self-limited, increased severity, increased risk of liver failure, rate of progression to chronic no different
What can an HDV superinfection cause?
- Convert mild chronic HBV hepatitis →acute liver failure (7-10%)
- Cause acute hepatitis to erupt in a healthy, inactive HBV carrier
- → chronic hepatitis (80%, compared to 4% with HBV alone)
- Carrier state also exists
How is HEV transmitted?
Fecal oral
What population can HEV cause mortality in?
Generally self-limited, but can cause mortality in pregnant women
Does NOT cause chronic hepatitis or carrier state
Very prevalent in underdeveloped countries
Very rare in US
We have vaccines for all forms of hepatitis except?
HCV
HEV does have a vaccine but is not available commercially
What serological tests are used for HAV?
Infected pts develop Ab response
• IgM HAV preceeds IgG HAV
• IgG persists & provides protective immunity
How do you dx HAV?
pt w/ clinical features of acute hepatitis & positive test for IgM anti-HAV.
Describe the serological tests associated w/ HBV. HBsAg HBeAg and HBV DNA IgM anti-HBc IgG anti HBc Anti HBs Anti HBe
HBsAg-ongoing HBV infection
HBeAg and HBV DNA- active viral replication, progression to chronic hepatitis
IgM anti-HBc- acute hepatitis
IgG anti HBc- past exposure to HBV
Anti HBs- recovery and immunity from HBV infection
Anti HBe- infection is resolving
How do you dx acute HBV?
Acute Hepatitis B = pt w/ clinical features HBsAg IgM anti-HBc both positive
*If pt has + HBsAg, but – IgM anti-HBc → think chronic hepatitis or carrier state
How do you dx chronic HBV?
clinical features & HBsAg + for > 6 mo.
• Also order HBeAg & HBV DNA to look for active viral replication
What serologic tests are used for HCV?
Anti-HCV Ab develop 10 wks post infection, do NOT confer recovery or immunity in most pts
What is the preferred screening test for HCV?
Ab detection using immunoassays = preferred screening test
How do you confirm an active HCV infection?
Active infection confirmed by measuring viral load by HCV PCR – used to assess response to therapy
Describe the serologic tests associated w/ HDV. IgM anti-HDV IgG anti-HDV Anti-HDV HDAg and HDV RNA
IgM anti-HDV- acute or recent HDV
IgG anti-HDV- previous infection w/ HDV, confers immunity
Anti-HDV- acute or chronic exposure
HDAg and HDV RNA- acute viral replication, ongoing infection
What serological marker persists in superinfecions w/ chronic HDV?
IgM anti-HDV can also persist
How do you dx HDV?
HBsAg positive Evidence of HDV infection — HDAg or HD RNA positive — IgM anti-HDV positive — anti-HDV positive
What marks an HDV coinfection?
IgM anti-HBc positive (acute or recent HBV
What marks an HDV superinfection?
IgM anti-HBc negative (chronic HBV)
How do you test for HDV?
— pts w/ high risk factors
— Present w/ unusually severe sx
— Acute hepatitis occurring in chronic HBV carrier
How do you detect acute HEV infections?
anti-IgM HEV & HEV RNA
WHat are the tests used to screen blood to avoid transfusion trasnmitted hepatitis?
- HBsAg
- anti-HBc
- HBV DNA
- anti-HCV
- HCV RNA
How is perinatally acquired HBV prevented?
Infants of mothers who are positive for hepatitis B surface antigen should receive hepatitis B immune globulin and hepatitis B vaccination within 12 hours of birth, and other infants should receive hepatitis B vaccination before hospital discharge.
What is the incubation phase of acute viral hepatitis?
variable, dependent on viral type
What are the 4 phases of the clincial presentation of acute viral hepatitis?
- Incubation phase: variable, dependent on viral type
- Preicteric prodrome: nonspecific, constitutional symptoms (malaise, fatigue, nausea, loss of appetite, arthralgias etc.); elevated serum levels of liver enzymes (ALT: alanine aminotransferase; AST: aspartate aminotransferase).
- Icteric (jaundice) phase: jaundice is not always present (anicteric hepatitis); conjugated hyperbilirubinemia mainly; dark urine (bilirubinuria).
- Convalescence (recovery) vs. acute liver failure vs. chronic hepatitis (with or without progression to cirrhosis) vs. “healthy” carrier.
How do you assess hte degree of liver damage w/ chronic viral hepatitis?
liver biopsy
clinical findings are highly variable
What are hte pathological findings associated w/ acute viral hepatitis?
lobular hepatitis
o Diffuse liver cell degeneration (ballooning degeneration)
o Focal hepatocellular necrosis (“dropout necrosis” – loss of hepatocytes) & apoptosis (councilman bodies)
o Confluent necrosis (seen in severe cases)
o Kupffer cell hyperplasia and hepatocellular regeneration
o Mononuclear inflammation (predominantly lymphocytes) w/in portal tracts and lobules
o “Lobular disarray”
Is acute viral hepatitis biopsied?
No
What defines chronic viral hepatitis?
hepatitis lasting more than 6 mos.
What pathological findings are associated w/ chronic hepatitis and ongoing necroinflammatory changes?
Periportal hepatitis
o Piecemeal necrosis
o Bridging necrosis & progressive fibrosis between periportal tracts → cirrhosis (severe cases)
Why is a biopsy required to assess liver damage in chronic viral hepatitis?
clinical findings of chronic viral hepatitis are highly variable
What is a councilman body?
apoptotic body in chronic viral hepatitis
Ground glass hepatocytes are associated w/…
chronic HBV
Spotty, focal pattern of mild periportal hepatitis with mild steatosis is associated w…
chronic HCV
What are some of the causes of acute massive hepatic necrosis?
o Acute viral hepatitis o Drug/toxin induced hepatitis (acetaminophen OD = 50%) o Vascular liver diseases o Autoimmune hepatitis o Wilson’s disease
If patients w/ acute massive hepatic necrosis survive, do they always get cirrhosis?
NO!
Pts suffer from acute liver failure
If pt survives, may not cause cirrhosis (if toxic agengent doesn’t cause fibrosis, liver can regenerate normally)
What abs are used to dx type 1 autoimmune hepatitis?
Type 1:
anti-nuclear (ANA),
anti-smooth muscle actin (SMA)
anti-soluble liver antigen/liver-pancreas (anti-SLA/LP) antibodies
What abs are used to dx type 2 autoimmune hepatitis?
Type 2:
anti-liver/kidney microsome-1 (anti-ALKM-1)
&/or
antibodies to a liver cytosol antigen (ALC-1)
What features seen on biopsy may suggest a dx of AIH?
Chronic hepatitis with increased plasma cells in the periportal lymphocytic inflammatory infiltrate along with lobular inflammation
What is the MC AIH and who does it commonly affect?
Type I
middle aged females
type II (children and adolescents)
How do you tx AIH?
immunosuppressive steroids
Differs from chronic viral hepatitis b/c you wouldn’t want to suppress the immune system to fight infxn.
What is seen on an acute hepatitis paneL/
- IgM anti-HAV
- HBsAg
- IgM anti-HBc
- Anti-HCV
What is seen on a chronic hepatitis panel?
- HBsAg
- Anti-HBs
- Anti-HBc
- Anti-HCV
