deck_5597883 Flashcards
What is cholestasis?
cholestasis= when there is systemic retention of not only bilirubin but also other solutes eliminated in bile.
What are the main functions of bile?
(1) the emulsification of dietary fat in the lumen of the gut through the detergent action of bile salts, and(2) the elimination of bilirubin and other waste products
When does jaundice occur?
Jaundice occurs when there is bilirubin overproduction, hepatitis, or obstruction of the flow of bileDisruption of the equilibrium between bilirubin production and clearance.
What are some pathologies that lead to jaundice via excess production of bilirubin?
Hemolytic anemiasResorption of blood from internal hemorrhage (e.g., alimentary tract bleeding, hematomas)Ineffective erythropoiesis (e.g., pernicious anemia, thalassemia)
What are some pathologies that lead to jaundice via reduced hepatic uptake of bilirubin?
Drug interference with membrane carrier systemsSome cases of Gilbert syndrome
What is Gilbert Syndrome?
Gilbert’s syndrome(GS) is a common geneticliver disorderfound in 3-12% of the population.It produces elevated levels of unconjugated bilirubin in the bloodstream (hyperbilirubinemia), but this normally has no serious consequences, although mildjaundicemay appear under conditions of exertion or stress.
What causes the hyperbilirubinemia in Gilbert syndrome?
The cause of this hyperbilirubinemia is the reduced activity of theenzyme glucuronyltransferase (UGT1A1),whichconjugates bilirubin in the liver and a few other lipophilic molecules. Conjugation renders the bilirubin water-soluble, after which it is excreted inbileinto theduodenum. There are a number of variants of the gene for the enzyme, so the genetic basis of the condition is complex.Similar to Type II Crigler-Najjar Syndrome
What are some pathologies that lead to jaundice via impaired bilirubin conjugation?
Physiologic jaundice of the newborn (decreased UGT1A1 activity, decreased excretion)Breast milk jaundice (β-glucuronidases in milk)Genetic deficiency of UGT1A1 activity (Crigler-Najjar syndrome types I and II)Gilbert syndromeDiffuse hepatocellular disease
What is the function ofUGT1A1?
TheUGT1A1gene belongs to a family of genes that provide instructions for making enzymes called UDP-glucuronosyltransferases. These enzymes perform a chemical reaction called glucuronidation, in which a compound called glucuronic acid is attached (conjugated) to one of a number of different substances.The protein produced from theUGT1A1gene, called the bilirubin uridine diphosphate glucuronosyl transferase (bilirubin-UGT) enzyme, is the only enzyme that glucuronidates bilirubin, a substance produced when red blood cells are broken down. This enzyme converts the toxic form of bilirubin (unconjugated bilirubin) to its nontoxic form (conjugated bilirubin), making it able to be dissolved and removed from the body.
Describe Type I Crigler Najjar syndrome
AR genetic disease marked by absence of UGT1A1 activity that is fatal to neonates
Describe Type II Crigler Najjar syndrome
AD disease (with variable penetrance) that is marked by decreased UGT1A1 activity causing mild kernicterus
What iskernicterus?
bilirubin-induced brain dysfunction
What is Dubin Johnson Syndrome?
An AR disorder marked byImpaired biliary excretion of bilirubin glucuronides due to mutation in canalicular multidrug resistance protein 2 (MRP2)
What is Rotor Syndrome?
An AR disorder marked by increases in conjugated bilirubin levels andnon-itchingjaundice
How is Rotor Syndrome differentiated from Dubin-Johnson Syndrome?
What is this?
Dubin-Johnson Syndrome-impaired excretion due to canalicular membrane-carrier defect, have darkly pigmented cytoplasmic globules in liver
What is this?
•Cholestasis - caused by impaired bile formation and bile flow that gives rise to accumulation of bile pigment in the hepatic parenchyma.
What is this showing?
Acute large duct obstruction-There is marked edema of the portal tract stroma (white spaces) and a ductular reaction with admixed neutrophils at the interface between portal tract and hepatocellular parenchyma.
Describe ascending cholangitis
•Individuals with large bile duct obstruction risk bacterial infections of the static bile within the biliary tree.•Enteric organisms such as coliforms and enterococci are common culprits.
What is the result of untx ascending cholangitis/duct obstruction?
•Ductular reactions initiate periportal fibrosis, eventually leading to hepatic scarring and nodule formation, generatingsecondary or obstructive biliary cirrhosis.
What is this?
biliary cirrhosis-Unlike other forms of cirrhosis, nodules of liver cells in biliary cirrhosis are often not round but irregular, like jigsaw puzzle shapes
What are the histo features ofchronic biliary obstruction?
-feathery degeneration of periportal hepatocytes-cytoplasmic swelling often withMallory-Denk bodies(differing from those in alcohol-induced liver disease and non-alcoholic fatty liver disease by their periportal predominance), and-formation ofbile infarcts
Cholestasis is also seen in sepsis most often due to in response to circulating microbial products. What is the most common form?
•The most common form iscanalicular cholestasis,with bile plugs within predominantly centrilobular canaliculi.
What is this?
•Ductular cholestasis- ominous•dilated canals of Hering and bile ductules at the interface of portal tracts and parenchyma become dilated•contain obvious bile plugs (Fig).Not a typical feature of biliary obstruction, but septic shock
What isHepatolithiasis?
is the presence ofgallstonesin thebiliary ductsof theliver.
What does primary hepatolithiasis lead to?
-repeated bouts of ascending cholangitis,-progressive inflammatory destruction of hepatic parenchyma, and-predisposes to biliary neoplasia
What does this show?
atrophic right hepatic lobe with characteristic findings of primary hepatolithiasis including markedly dilated and distorted bile ducts containing large pigment stones and broad areas of collapsed liver parenchyma.
What does this show?
Neonatal Cholestasis caused by neonatal hepatitis-persisting conjugatedhyperbilirubinemiain thenewbornwith conjugatedbilirubinlevels exceeding 15% (5.0mg/dL) of total bilirubin level.
