Jaundice harrison's Flashcards
Bilirubin level if you have scleal icterus
51 umol/L or 3mg/dL
Green color is produced by oxidation of bilirubin to
Biliverdin
Drug that causes skin discoloration in 4-37%
Quinacrine
Yellowing of the skin that is concentrated on palms, soles, forehead, nasolabial fold and sparing of the sclerae
Carotenoderma
Each day about 250/300mg of bilirubin is produced and ___% is from the breakdown of hemoglobin (heme)
70-80%
Another name for heme
Ferroprotoporphyrin IX
Formation of bilirubin occurs in which cellsnin which organs
Reticuloendorhelial cells
Spleen/liver
First reaction in metabolism of bilirubin is the cleaving of the alpha bridge of the porphyrin group opening the heme ring prodicing 3:
Iron
Carbon monoxide
Biliverdin
Converts biliverdin to bilirubin
Biliverdin reductase
The conjugation of glucoronic acid to bilirubin is catalyzed by
UDPGT
uridine diphosphate glucoronyl transferase
Where is bilirubin hydrolyzed to unconjugated bilirubin and by what enzyme
Distal ileum and colon
Bacterial beta glucuronidases
Urobilirubin is reduced by normal gut bacteria to urobilinogens and this is excreted in three ways
80-90% feces
10-20 passiveley absorbed and are re excreted by the kiver
<3mg/dL escapes hepatic uptake and is excreted in urine
Half life of bilirubin
4 h
Drugs that cause problem with hepatic uptake or conjugation of bilirubin causing unconjugated hyperbilirubinemia
Rifampicin
Probenacid
Ribavirin
Complete absence if UDPGT activity due to mutations in the critical 3’ domain of the UDPGT gene
Found in neonates
Kernicterus
Death in infancy or childhood
Crigler-Najjar Type I
Reduction of UDPGT activity but patients survive into adulthood
Serum bilirubin of 6-25mgdL
Crigler-Najjar Type II
Reduced UDPGT activity but serum lbilirubin usually <6 (mild hyperbilirubinemia) sue to impairment in transcription of bilirubin UDPGT gene
impaired conjugation of bilirubin due to reduced bilirubin UDPGT activity (typically 10–35% of normal).
Jaundice during periods of fasting, stress, alcohol
Gilbert’s syndrome
Incidence of gilbert’s symptoms
3-7%
2-7:1 (Male to female)
Asymptomatic jaundice
Altered excretion of bilirubin into the bile ducts
Dubin-Johnson syndrome
Gene affected in dubin johnson
MRP2 gene mutation
Asymptomatic jaundice with deficiency in major hepatic drug uptake transporters OATP1B1 and OATP1B3
Rotor Syndrome
Alcoholic cirrhosis
Another name
Laennec’s
Alcoholic hepatitis has an AST/ALT ratio of
2:1
Screening for Wilson’s Disease
Ceruloplasmin
Hepatoroxin in Jamaic bush tra or kava kava
Pyrrolizidine alkaloids
Chronic Cholestasis associated with which drugs
Chlorpromazine and prochlorperazine
autoimmune disease p inantly affecting middle-aged women and characterized by progressive Destruction of interlobar bile ducts
+ antimitochondrial antibody 95%
Promary biliary cirrhosis
Destruction and fibrosis of larger bile ducts
Has pathognomonic segmental strictures
Associated with IBD and cholangiocarcinoma.
Prinary sclerosing cholangitis
Percentage of patients with PSC eith IBD
75%
Progressive familial intrahepatic cholestasis types 1 choldhood) and benign recurrent cholestasis (adulthood) has this gene mutation
ATP8B1 gene (encodes P type ATPases)
PFIC2 gene mutation
ABCB11 gene
PFIC3 mutation
P-glycoprotein 3
Intrahepatic choletasis that is associated with renal cell cancer
Stauffer’s syndrome
Most common cause of extrahepatic cholestasis
Choledocholithiasis
Differentials for Yellowing of the skin
carotenoderma, the use of the drug quinacrine, and excessive exposure to phenols
half life albumin
12-14 hours
Unconjugated bilirubin is always bound to albumin in the serum, is not filtered by the kidney, and is not found in the urine.
t
A false-negative result is possible in patients with prolonged cholestasis due to the predominance of delta bilirubin, which is covalently bound to albumin and therefore not filtered by the renal glomeruli.
t
In evaluating jaundice in patients with chronic hemolysis, it is important to remember the high incidence of pigmented (calcium bilirubinate) gallstones found in these patients,
t
Impaired bilirubin conjugation occurs in three genetic conditions:
Crigler-Najjar syndrome types I and II and Gilbert’s syndrome.
Bilirubin UDPGT activity can be induced by the a tration of phenobarbital, which can reduce serum bilirubin levels in these patients.
phenobarbital,
dRUGS Causing indirect hyperbole
- Rifampin
- Probenecid
- Ribavirin
- Protease inhibitors (Atazanavir, Indinavir)
Dubin Johnson and Rotor syndrome both have asymptomatic jaundice
TRUE
. A history of arthralgias and myalgias predating jaundice suggests hepatitis, either viral or drug-related.
true
Stigmata of chronic liver disease
spider nevi, palmar erythema, gynecomastia, caput medusae, Dupuytren’s contractures, parotid gland enlargement, and testicular atrophy, are commonly seen in advanced alcoholic (Laennec’s) cirrhosis and occasionally in other types of cirrhosis
vThe absence of biliary dilation suggests intrahepatic cholestasis, while its presence indicates extrahepatic cholestasis.
t
CT scanning and MRCP are better than ultrasonography for assessing the head of the pancreas and for identifying choledocholithiasis in the distal common bile duct, particularly when the ducts are not dilated.
t
the “gold standard” for identifying c holedocholithiasis
ERCP
. Both hepatitis B and C viruses can cause cholestatic hepatitis (fibrosing cholestatic hepatitis) seen in which population
patients who have undergone solid organ t plantation
anabolic and contraceptive steroids cause what kind of drug toxicity
Pure cholestasis
chlorpromazine, imipramine, tolbutamide, sulindac, cimetidine, and erythromycin estolate, trimethoprim; s azole;; and penicillin-based antibiotics such as ampicillin, dicloxacillin, and clavulanic acid
Cholestatic hepatitis
Chronic cholestasis
chlorpromazine and prochlorperazine
rare conditions in which a decreased number of bile ducts are seen in liver biopsy specimens
This picture is seen in patients who develop chronic rejection after liver transplantation and in those who develop graft-versus-host disease after bone marrow transplantation.
also occurs in rare cases of sarcoidosis,
vanishing bile duct syndrome and adult bile ductopenia
characterized by episodic attacks of pruritus, cholestasis, and jaundice beginning at any age, which can be debilitating but does not lead to chronic liver disease. Serum bile acids are elevated during episodes, but serum γ-glutamyltransferase (γ-GT) activity is normal.
benign recurrent i hepatic cholestasis (BRIC) types 1 and 2.
d orders begin at childhood and are progressive in nature. All three types of PFIC are associated with progressive cholestasis, elevated levels of serum bile acids, similar phenotypes but different genetic mutations. Only type 3 PFIC is associated with high levels of γ-GT
progressive f ial intrahepatic cholestasis (PFIC) types 1–3
occurs in the second and third trimesters and resolves after delivery. Its cause is unknown, but the condition is probably inherited, and cholestasis can be triggered by estrogen administration.
Cholestasis of pregnancy
Other causes of intrahepatic cholestasis paraneoplastic syndrome associated with a number of different malignancies
number of different malignancies, including Hodgkin’s disease, medullary thyroid cancer, renal cell cancer, renal sarcoma, T cell lymphoma, prostate cancer, and several gastrointestinal malignancies.
cholestasis in the intensive care unit, the major considerations should be
sepsis, ischemic hepatitis (“shock liver”), and TPN jaundice
Jaundice occurring after bone marrow transplantation is most likely due to
eno-occlusive disease or graft-versus-host disease.
Plasmodium falciparum malaria
The jaundice in these cases is due to a combination of indirect hyperbilirubinemia from hemolysis and both cholestatic and hepatocellular jaundice.
has the highest surgical cure rate of all the tumors that present as painless jaundice
Ampullary carcinoma
is the most common cause of extrahepatic cholestasis.
Choledocholithiasis
is a condition that is usually due to infection of the bile duct epithelium with CMV or cryptosporidia and has a cholangiographic appearance similar to that of PSC. The affected patients usually present with greatly elevated serum alkaline phosphatase levels (mean, 800 IU/L), but the bilirubin level is often near normal. These patients do not typically present with jaundice.
AIDS cholangiopathy
