Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
35 Cards in this Set
- Front
- Back
|
Mutations in the HFE gene are responsible for which liver dz?
Explain the pathogenesis and the 2 postulated mechanisms of disease progression. Inheritance pattern? |
HHC
HFE: nonclassical MHC class I molecule; cmplxes w/ transferring receptor (TfR1) --> facilitates uptake of iron. - Muts in this gene impair b/ing 1.Cells sense iron deficiency, signal with DMT1 for more intestinal Fe abs. 2. not enough hepcidin --> it can't downregulate Fe absorption... - hepcidin also is supposed to limit the export of Fe from enterocytes and macrophages... so without it, there is too much release --> more abs. autosomal recessive. |
|
|
What is the most common autosomal recessive dz in Caucasians?
Which sex presents later with this dz? Why is it important to think about this dz early in the diffdx? |
HHC
Women, because menstruation allows them to lose some iron. It's tx'able with phlebotomy, but it can present asymptomatically in up to 75%. |
|
|
28-yo male presents with elevated ALT, Hepatomegaly, and some joint pain.
Would you run iron labs on this pt? Which? Why? Are the arthropathies reversible? Can the dz we're worried about in this pt have any cardiac sequelae? If they're present, are they reversible? Can these pts have hypogonadism? |
Yes, may have HHC.
Fe / TIBC; serum ferritin No. Yes, dilated cardiomyopathy, conduction disturbances. Yes. Yes, dues to direct deposition and pituitary deposition --> \FSH, \LH |
|
|
What is the gold standard of dx for HHC?
|
Liver Biopsy -->
- Hepatic iron content (HIC) - Hepatic Iron Index (HII) |
|
|
What dz is characterized by a failure of hepatocytes to excrete copper into biliary canaliculi, as well as a mut in ATP7B on Crm 13?
Which age group does this dz affect? |
Wilson's Dz.
<30y, M>F |
|
|
What are Kayser-Fleischer Rings and which dz do they associate with?
|
golden-brown pigment around periphery of cornea
Wilson's Dz |
|
|
26 yo Male presents with hemolytic anemia, tremors, and fulminant ALF.
Which dz should be foremost on your mind? How would you make the dx? What is the relationship of alk-phos lvls to total bili lvls in this dz? What is the gold standard of dx? |
Wilson's Dz.
test for low serum ceruloplasmin High serum copper high urine copper usually relatively low alk-phos and high total bili Liver Biopsy; do NOT use unless needed |
|
|
Is elevated serum copper lvls a specific indicator of Wilson's dz?
|
no, other things can elevated those lvls, like chronic cholestatic dz, etc.
|
|
|
What is the tx of Wilson's dz?
|
Copper chelation:
D-penicillamine, Trientine, Zinc bad enough --> liver txplt |
|
|
Lung dz associated with a1 antitrypin mutations are due to what?
Liver dz? What can be noted on histological specimens that can suggest this dz? |
low circulating A1AT
Buildup of A1AT in the liver b/c it cannot be secreted eosinophilic cytoplasma granules (fuzzy) |
|
|
Can Heterozygotes for A1AT get liver sx of the dz?
Do homozygotes (ZZ) for this autosomal recessive disorder always get liver dz? |
not unless there is another liver problem like alcohol abuse.
No. |
|
|
How do you have to make the dx of Granulomatous hepatitis?
|
Pathologically
|
|
|
Tell me which dz the following sx/labs typically describe:
fatigue pruritus jaundice elevated alk-phos NORMAL aminotransferase Elevated ACE |
Sarcoid or Primary biliary cirrhosis (PBC); could be another granulomatous dz if the ACE lvls were more normal.
|
|
|
Which dz is associated with "clay pipe stem" fibrosis, which describes marked portal fibrosis w/calcification?
What other sx commonly present with this dz? |
Schistosomiasis
Hepatosplenomegaly Portal HTN w/ esophageal varicies |
|
|
What is the pathophysiology of PBC?
Gender predisposition? Age? |
Destruction of small intrahepatic bile ducts à cholestasis (impaired bile flow)
- impaired fat absorption 95% female; most b/t 40-60 |
|
|
What is Xanthelasma?
Which dz is it associated with? Is this dz autoimmune? Etiology? |
yellow eyelids and weird growths on the skin as a result of impaired metabolism of cholesterol seen in PBC.
Yes. Unknown. |
|
|
53yo Woman presents with fatigue, and occasional pruritus.
Lab values: - High AMA - High Alk phos - norm/mod.high transaminases - elevated Serum IgM Which dz should be first on your mind? How is a definitive dx made? Negative prognostic indicators? (2) |
PBC
Exclusion w/ evaluation of the biliary tree (rule out larger obstruction such as gallstones, etc.) Jaundice, cirrhosis |
|
|
What are some of the complications of fat malabsorption seen in PBC? (3)
Can Portal HTN (and it's associated complications) also be seen in PBC? |
weight loss, steatorrhea, fatsol vitamin deficiency
Yes, later on in the dz progression. |
|
|
Do AMA lvls predict survival in PBC patients?
What is the tx for PBC? Does it delay dz progression? improve survival? Are steroids indicated? Transplant? |
No.
Bear Bile! (Ursodiol) may do both, if given early enough. No, contraindicated. Yes, for advanced enough dz |
|
|
Of the four following dz, which can be tx'ed with liver txplt?
Hereditary hemochromatosis Wilson’s disease Alpha-1-antitrypsin deficiency Granulomatous hepatitis |
Wilson's and A1AT can be tx'ed with txplt.
The liver is a 'bystander' in the other two disorders. |
|
|
What can cholestyramine help tx? How does it work? Can it be given at the same time as something like ursadiol?
|
Pruritis from liver failure (which occurs because the liver can't eliminate bile)
Bileacid b/ing agent No, it would b/ that and defeat the point. |
|
|
Which inflammatory, probably autoimmune dz is chacterized by obliteration of medium-sized and/or large biliary (intra- and/or extrahepatic) ducts --> cholestasis?
|
Primary Sclerosing Cholangitis (PSC)
|
|
|
PSC:
- gender? - age? - does it present early or late? Why do we think this may be? What does this mean re: jaundice? |
- men!
- 20-40y, usually - later, maybe because men wait longer before going to the doctor. Jaundice is seen more often in PSC than PBC, most likely as a result of this skew. |
|
|
~75% of those with PSC have what other dz?
Is the converse true? |
ulcerative colitis (UC)
no, only ~5% of those with UC have PSC. |
|
|
A 47 year-old male athlete walks into your clinic with jaundice and fatigue. Which of the following is he most likely to have:
Primary biliary cirrhosis Primary sclerosing cholangitis Autoimmune hepatitis |
PSC
|
|
|
Fatigue, itching, jaundice, fever/chills, RUQ pain (from Hepatomegaly)....
Can these Sx describe PSC? |
yes, but note that they're very unspecific.
|
|
|
In which dz are history and serology more helpful: PSC or PBC?
What lab values are helpful in PSC? |
PBC
elevated serum alk-phos out of proportion to AST/ALT (same as PBC) p-ANCA (80% sensitivity) Hypergammaglobulinemia Other autoantibodies. ..... Gotta Rule out secondary causes as well.... |
|
|
Is Ultrasound dx of PSC? What is?
What is seen in the case of dz? |
No.
Cholangiography (imaging of bile vessels) - using ERCP (old way) or MRCP (becoming more accepted) Multifocal stricturing and dilation of intrahepatic +/or extrahepatic bile ducts “Beads-on-a-string” |
|
|
If PSC pts have UC (ulcerative colitis) as well, which complication become far more likely?
Does just PSC predispose you to Choloangiocarcinoma? |
Colon cancer
Yes. |
|
|
The natural hx of PSC is a slowly progressive dz with a med. survival/time to txplt of 12yrs from dx. What is acute deterioration in this dz a sign of?
Does Tx of PSC help? Should ursodiol, colchicine, or methotrexate be used? |
poor prog, often heralds the development of cholangiocarcinoma
It doesn't impact progression of dz. Not effective; Ursadiol was recently shown to have adverse effects on life expectancy. |
|
|
Which autoimmune dz of the liver produces hepatocellular injury, not cholestatic dz?
|
Autoimmune Hepatitis
|
|
|
Can PBC or PSC lead to fulminant hepatitis? Autoimmune Hepatitis?
Are the follow sx possible for autoimmune hepatitis? Fatigue, malaise Nausea Abdominal pain Pruritus Jaundice Hepatomegaly Arthralgias signs of chronic liver dz fulminant hepatitis |
He doesn't think so.
Yes, it can. Yes, all are - not that arthralgias can show up here too! |
|
|
Elevated AST and ALT; disproportionate to alk phos and bilirubin
elevated ANA > 1:80 Elevated Immunoglobulins Negative HBV and HCV testing What should we think? What does a liver biopsy show in this dz? |
Autoimmune hepatitis
plasma cells |
|
|
Type I autoimmune hepatitis is ANA __, ASMA __, and Anti-LKM (liver, kidney, muscle) __.
Type II? |
+ + -
- - + |
|
|
The natural hx of autoimmune hepatitis:
Can be relatively asymptomatic, or have protean symptoms Relapsing and remitting course with elevations in AST/ALT Progressive evolution to fibrosis and cirrhosis ...tx's? (1st line and 2nd) |
1st: immunosuppression
2nd: cycolosporine, tacrolimus, mycophenolate mofetil (these are used only in refractory dz) |
