18.4

Question 1

what is the pathophys of jaundice

Answer 1

two fxns of bile: 1. Emulsification of fats through detergent action of bile salts, enabling its abs in the gut lumen and 2. Elimination of bilirubin, excess cholesterol, xenobiotics, trace metals and other waste products that are insufficiently water-soluble to be excreted in the urine.

Breakdown of heme (RBC) by macrophages in the liver (& spleen/bone marrow) produces bilirubin, a toxic end product. It is then taken from circulation, intracell storage, conjugation via glucuronic acid and then excreted in bile. If serum bilirubin rises to 2-2.5 mg/dL, pt can present w/ jaundice.

Question 2

what is unconjugated hyperbili?

what dz’s are associated w/ this

Answer 2

= insoluble and unable to be excreted in the urine

tightly bound to albumin in the blood, however excess levels cause increase in unbound unconjugated bilirubin–> diffuse into the tissues (esp in the brain of infants- fetal hydrops) and cause neuro damage (kernicterus)

causes: excess prodcution, reduced uptake, impaired conjugation

Question 3

differentiate crigler najjar I and II and gilbert syndrome

Answer 3

Question 4

what is conjugated hyperbili?

what are causes of this

Answer 4

hepatocellular dz, bile duct injury and biliary obstruction

= water-soluble and loosely bound to albumin, so can be excreted in the urine

Causes: def in canalicular membrane transport, hepatocell dz, impaired bile flow from obstruction or AI cholangiopathies

Question 5

compare/contrast dubin johnson and rotor syndrome

Answer 5

Question 6

what is cholestasis

what are hallmarks, causes and complications?

Answer 6

Decrease in bile flow due to impaired secretion by hepatocytes or obstruction of flow through intra/extrahepatic ducts.

Hallmark = green-brown plug of bile pigment in hepatocytes and dilated canaliculi

due to primary hepatolithiasis or sepsis- intrahepatic infxn, ischemia or microbial products (MCC, esp w/ gram (-))

high prevalent in E. Asia –> increased risk for cholangioCA

Question 7

what is the morphology of hepatocytes in cholestasis

Answer 7

enlarged cells w/ dilated canalicular spaces, possible apoptotic cells, possible kupffer cells, and freq involvement of regurgitates bile pigments

Question 8

what is the etiology of cholestasis in adults

Answer 8

Obstruction due to:

1. Stone (extrahepatic cholelithasis)
2. Tumor (malignancy of biliary tree or pancreas)
3. Strictures

Question 9

what is the consequence of persistent obstruction in cholestasis

Answer 9

Persistent obstruction can lead to fibrosis and biliary cirrhosis

increase chance of ascending cholangitis- a bacterial infxn of the biliary tree caused by enteric organisms (coliforms and enterococci),

Question 10

what are histology hallmarks of ascending cholangitis

Answer 10

influx of periductal neutrophils directly into the bile duct epithelium and lumen

Question 11

how does ascending cholangitis present

Answer 11

“Charcot’s triad”- fever, RUQ abd pain, jaundice

& severe cases (suppurative cholangitis - purulent bile fills/distend bile duct)- abscess, sepsis, death

Question 12

what are causes of neonatal cholestasis

Answer 12

obstruction (biliary atresia)

non obstruction (Alegielle syndrome - paucity of bile duct, infxn/metabolic, genetic, idiopathic)

Question 13

what is biliary atresia

Answer 13

complete/partial obstruction of lumen of EXTRAhepatic biliary tree

w/i 1st 3 months of life → W/O SRG = DEATH

MCC death by liver dz in early childhood

could be perinatal (MCC- infxn, toxin or AI) or fetal (ineffective establishment of laterality of thoracic and abd organs during development)

Question 14

what are effects of elevated bilirubin

Answer 14

jaundice, icterus,

pruritus,

skin xanthomas (focal accumulation of cholesterol),

malabs (fat soluble - ADK)

Question 15

what are characterisic lab findings in cholestatis

Answer 15

increased ALP and GGT enzymes on canalicular (apical) membrane of hepatocytes and bile duct epithelial cells