Flashcards in EXAM #2: LIVER PATHOLOGY Deck (73)
What are the four most common causes of chronic liver disease in US? (List in order of prevalence)
1) Hepatitis C
2) Alcoholic liver disease
3) Non-alcoholic fatty liver disease
4) Hepatitis B
What is meant by hepatocyte integrity?
Membrane integrity of hepatocytes
****When damaged, hepatocytes are "leaky"****
What are the two classic liver lab tests?
*****Finding these enzymes in the serum indicates that there has been damage to the hepatocytes that have made them "leaky"*****
What three lab tests test hepatocyte function? What happens to these tests with impaired liver function?
1) Serum albumin--decreased
2) Prothrombin time--increased
3) Serum ammonia--increased
What lab tests are associated with obstructed bile flow?
2) 5'-Nucleotidase (5'-NT)
What are the two types of bilirubin? What is the difference between direct and indirect bilirubin?
- Conjugated= Direct, has sugar moieties added and can be excreted
- Unconjugated= Indirect, no sugar moieties
*****Unconjugated is "indirect" b/c it is an indirect measurement (Total- conjugated= unconjugated)*****
What is the normal serum total bilirubin level?
What are the clinical manifestations of hyperbilirubinemia?
- Cholestasis= slowing of the flow of bile
How high does the serum bilirubin need to be for there to be clinical symptoms?
Carvenale= greater than 2 mg/dL
Pathoma= greater than 2.5 mg/dL
Outline normal bilirubin metabolism.
1) RBCs are consumed by splenic macrophages
2) Protoporphyrin (from heme) is converted into UNCONJUGATED bilirubin (UCB)
- Heme oxygenase= Biliverdin
- Biliverdin reductase= Unconjugated Bilirubin
3) UCB binds albumin and is carried to the liver
4) In the hepatocyte ER, UCB is CONJUGATED to CB, via Uridine Glucuronyl Transferase (UGT)
5) CB is transferred to bili canaliculi via MDR-2 and MDR-3 transporters to form bile
6) Bile is stored in the gallbladder
7) Bile is released into the duodenum
8) Intestinal flora convert CB to UROBILINOGEN in the bowel
9) Urobilinogen is oxidized to STERCOBILIN and UROBILIN
What enzyme conjugates UCB in the hepatocyte?
UGT, Uridine Glucuronyl Transferase
- Adds one sugar to bilirubin i.e. monoglucuronides
- OR adds 2x sugars to make diglucuronides
What heme degradation product gives stool its color?
What heme degradation product gives urine its color?
What is the etiology of hyperbilirubinemia seen in extravascular hemolysis or ineffective erythropoiesis?
- Increased UCB b/c of heme degradation
- UCB overwhelms liver's ability to conjugate
What is the lab finding in extravascular hemolysis/ ineffective erythropoiesis?
What are the clinical features of extravascular hemolysis/ ineffective erythropoiesis?
1) Dark urine due to increased urine UROBILINOGEN
2) Increased risk for pigmented bilirubin gallstones (excess UCB must eventually be converted to CB--hyperaccumulation of which can cause gallstones)
****Note that UCB is NOT water soluble and will NOT be in urine****
What is the etiology of physiologic jaundice of the newborn?
Newborns have transiently low UGT (UCB-->CB)
What is the lab manifestation in physiologic jaundice of the newborn?
What is the clinical manifestation of physiologic jaundice in the newborn?
- UCB is fat soluble
- Deposits in the basal ganglia and causes neurologic deficits/death
How is physiologic jaundice of the newborn treated?
Phototherapy, which makes UCB more water souble
****Note that phototherapy does NOT conjugate UCB*****
What is the etiology of Gilbert Syndrome?
Mildly low UGT activity due to a promoter mutation
What is the inheritance pattern of Gilbert Syndrome?
What lab finding is associated with Gilbert Syndrome?
What are the clinical features associated with Gilbert Syndrome?
1) Predominantly asymptomatic
2) STRESS e.g. severe infection causes hyperbilirubinemia
What is the etiology of Crigler-Najjar Syndrome Type I?
Autosomal recessive absence of UGT
What is the lab finding in Crigler-Najjar Syndrome?
Extremely elevated UCB
What are the clinical manifestations of Crigler-Najjar Syndrome?
Kernicterius that is typically fatal
How does Crigler-Najjar Syndrome Type 2 differ from Type 1?
- AUTOSOMAL DOMINANT with variable penetrance
- Moderate decrease in UGT activity
- Only occasional kernicterus
****NOTE that this is TREATED WITH PHENOBARBITAL*****
What is the etiology of Dubin-Johnson Syndrome?
Autosomal recessive mutation in MDR-2 transporter that impairs CB transfer to bile canaliculi