Alcoholic, Metabolic, & Autoimmune Liver Disease - Franco Flashcards
Why is “primary biliary cirrhosis” a misnomer?
Describe this disease’s etiology.
There is generally little cirrhosis of the liver parenchyma
Usually autoimmune; IgM antimicrobial antibodies (AMA) target PDC-E2. (pyruvate dehydrogenase complex) on the canalicular
Describe the epidemiology of PBC. Who is affected and at what age?
Almost entirely (caucasian) women, mean age 52 at presentation.
(look for a familial pattern)
What are the expected lab findings in primary biliary cirrhosis?
What symptoms do the patients complain of?
Increased alkaline phosphatase (disease is cholestatic) and positive AMAs. Other autoimmune diseases may be copresent. Elevated cholesterol.
Lethargy and pruritus, some xanthomas/atheromas
Why does primary biliary cirrhosis result in fat soluble vitamin deficiency?
What are the consequences of this?
Biliary obstruction causes decreased bile salt excretion which reduces the ability for the GI tract to absorb lipids (and fat-soluble vitamins).
Vitamin D deficiency causes osteomalacia. Vitamin K deficiency causes prolonged bleeding (both uncommon)
What autoimmune diseases are most associated with primary biliary cirrhosis?
Sjogren’s disease > Thyroiditis > Rheumatoid Arthritis > many others…
Why does primary biliary cirrhosis result in intense pruritis?
With this in mind, give three treatment options that relieve this symptom.
The bile salts not excreted through the biliary tree accumulate elsewhere, eg in the skin and provoke itching.
Ursodeoxycholic acid (also improve labs and survival), cholestyramine (bind and remove more bile), diphenhydramine (anti-histamine and drowsy for nighttime relief)
What gene causes hereditary hemochromatosis?
What chromosome is the gene located on?
HFE gene
Short arm of chromosome 6
What does the HFE protein do?
Why does this cause hemochromatosis?
regulates the expression of transferrin
When iron levels in the blood are high, transferrin should be down-regulated; without functional HFE, transferrin levels stay high and iron accumulates
What causes secondary hemochromatosis?
Ineffective hematopoiesis
Liver disease
Red cell transfusions
Iron-dextran injections
Long-term dialysis
Who gets diagnosed with primary hemochromatosis?
What is the mutation?
Causcasians of northern european ancestry
C282Y/C282Y or
C282Y/H63D
What symptoms are seen in hemochromatosis?
Liver function abnormalities
Lethargy
Hyperpigmentation
Diabetes
Impotence
Arthralgia
(AKA bronze diabetes)
How does hemochromatosis present differently in women?
Typically presents later due to blood loss during menstrual cycle
What tests are needed to diagnoses hereditary hemochromatosis?
- Look at fasting transferrin saturation
- normal is <45%
- Genetic Testing
- if compound heterozygote, consider biopsy
- if homozygote, phlebotomy
- if homozygote over 40 or with elevated AST/ALT, biopsy
What stain is used with liver biopsys to see diagnose hemochromatosis?
How does iron appear with this stain?
Prussian Blue stain
Iron appears blue
How should phlebotomy be used to treat hemochromatosis?
Ferritin <50
Initially weekly, but moved to quarterly after stable levels reached
How is copper typically handled in a healthy human?
What is decreased in Wilson’s disease?
Bound to ceruloplasmin, excreted in bile, or excreted in urine
Ceruloplasmin levels are decreased and bile excretion is decreased
How common is Wilson’s disease?
Who should Wilson’s disease be considered in?
30 cases per million
patients age 30-40 with liver problems
Why is Wilson’s disease so difficult to diagnose?
Wide variety of neurological or psychiatric symptoms including:
Depression
Migraines
Insomnia
Psychosis
Movement disorders
Seizures
What can lead to false negatives in Wilson’s disease diagnoses?
Wilson’s disease typically has ceruloplasmin levels less than 20mg/dL, but inflammation raises levels
What are three physical signs of Wilson’s disease?
Urinary excretion of Copper
Kayser-Fleischer Rings
Increased copper concentration in liver biopsy
What three therapies are available for Wilson’s disease?
How do they work?
D-penicillamine- chelates copper and induces cupruria
Trientine-chelates copper and induces cupruria
Zinc- blocks absorption and induces metallothionein
(wikipedia has no entries on cupruria, but it brings up a lot of entries in Spanish)
What is Alpha-1 anti-trypsin?
What pathologies does alpha-1 anti-trypsin deficiency cause?
An elastase inhibitor
Hepatitis, cirrhosis, liver cancer, genetic emphysema
What are three gene variations associated with alpha-1 antitrypsin?
How do their severitys compare?
M- main or WT
S- uncommon mutant
Z-common mutant
MM>MS>MZ>SS (no lung or liver disease)
SZ> null-null (lung disease)
ZZ (lung and liver disease)
How does alpha-1 antitrypsin cause disease in the lungs?
How does it cause disease in the liver?
Loss-of-function; A1AT does not inhibit elastase and tissue is generally destroyed, causing emphysema
Protein accumulation; A1AT misfolds and accumulates in hepatocytes
How is Alpha-1 antitrypsin deficiency diagnosed?
Serum A1AT levels
A1AT genotyping
Liver biopsy to look for protein accumulation
What is autoimmune hepatitis?
What are some risk factors for autoimmune hepatitis?
inflammation of hepatocytes caused by autoantibodies in the serum
female, with other autoimmune diseases
What lab results are seen in autoimmune hepatitis?
What is seen on histology in autoimmune hepatitis?
- ALT, AST elelvation
- Elevated gamma-globulin or IgG
- Autoantibodies
- Interface hepatitis
- portal plasma cell infiltration