04b: Liver Stuff Flashcards
Liver disease longer than (X) period of time is considered chronic
X = 6 months
Patients considered to be in fulminant hepatic failure presented with which symptoms only (X) weeks after onset of liver disease.
X = 6
Encephalopathy, hypoglycemia, hypoalbuminemia, low coag factors
The jaundice seen in liver disease is almost always associated with which other symptom?
Dark urine (due to high direct BR)
T/F: pruritis and maculopapular rash are important features of liver disease
False - rash-less pruritis is
T/F: liver disease symptoms include hypercoaguable states
True - decreased synthesis of antithrombin III, Protein C and S
List the key clinical signs that make liver disease in a patient obvious.
- Jaundice
- Muscle wasting
- Ascites
- Palmar erythema
- Spider angioma
Enlargement of the spleen in the setting of liver disease is usually due to:
portal hypertension
A cirrhotic liver feels (X) upon palpating
Firm and nodular
Liver function tests usually include (X) hepatocellular enzymes and (Y) canalicular enzymes.
X = AST, ALT Y = ALP, GGT
Most commonly used tests of hepatic synthetic function include:
- Albumin
2. PT (replaced by INR)
Most commonly used tests of hepatic excretory function include:
BR
(ALT/AST) is less specific to liver since it is also found in high concentrations in (X) cells.
AST
Pancreas, RBCs, muscle, kidney
An increase in (AST/ALT) that’s out of proportion to (AST/ALT) suggests alcoholic hepatitis/drug-induced injury.
AST»_space; ALT
Likely due to extra-hepatic release as well
Increased levels of alkaline phosphatase is found as result of extra-hepatic reasons such as:
- bone disease (Paget’s)
- pregnancy
- intestinal injury (ischemia).
Increased levels of alkaline phosphatase (with normal AST/ALT) is found as result of hepatic diseases such as:
- Bile duct obstruction
2. Cholestatic liver diseases (primary biliary cirrhosis, sclerosing cholangitis, drug-induced cholestatic liver injury)
Hepatic cause for high ALP can be confirmed with (X) test.
X = GGT (should see parallel increase)
GGT is a (specific/sensitive) test for liver injury.
Sensitive (but not specific for any one disease since elevated in nearly all forms of liver disease)
T/F: liver disease can be ruled out with normal serum albumin levels.
False - long half-life of albumin means acute liver disease in patient may present with normal albumin
Based on the (short/long) half life of (X), which test is extremely useful for monitoring liver function in patients with acute liver injury?
Short;
X = clotting factors
PT/INR
List examples of diseases that present with hepatitic pattern of disease (high ALT/AST).
- Viral/autoimmune hepatitis
2. Acute drug toxicity (ex: acetaminophen)
List the most common diseases that would cause AST/ALT rise over 1000!
- Viral hepatitis
- Drug/toxin-mediated hepatitis
- Ischemic hepatitis
“Mixed” (cholestatic and hepatitic) pattern of liver disease is only really seen in which cases?
chronic diseases (cirrhosis, some cases of metastasis)
What are some causes for cholestatic pattern of liver disease (high ALP/GGT)?
- Bile duct obstruction
- Metastatic disease to liver
- Infiltrative disorders
- Granulomatous disease
- Autoimmune (preferentially affecting biliary ductules)
BR is formed from breakdown of:
Heme:
- Myoglobin
- Hemoglobin
- Cytochromes
T/F: Liver is major site of BR production.
False - spleen! 70-80% BR from hemoglobin from senescent RBCs
In ecchymoses (bruises), (X) process is occurring in (Y) cells.
X = Heme breakdown and BR formation Y = macrophages
BR formation: here is converted to (X) by (Y). What color is (X)?
X = biliverdin Y = heme oxygenase
Blue/green
Biliverdin is converted to (X) via cytosolic (Y).
X = BR Y = Biliverdin reductase
T/F: both biliverdin and BR are water insoluble.
False - biliverdin water soluble
Which structural feature of BR accounts for its poor water solubility?
Intramolecular H bonds
T/F: unconjugated BR is transported to liver bound to albumin
True
T/F: Hepatic uptake of BR is rate-limiting in its metabolism.
False - very rapid carrier mediated uptake
Once BR enters hepatocyte, (X) regulate its cytosolic diffusion and prevent efflux back into plasma.
X = ligandins and FA binding proteins (bind to BR)
BR conjugating enzyme:
UGT (BR Uridine diphosphate glucoronosyltransferase)
BRDG transported across (X) and into biliary tree via which transporter?
X = canalicular membrane
MRP2 transporter
In the gut, bacteria have which effect on BRDG?
- Deconjugation (back to BR)
2. Reduction (to urobilinogen)
T/F: Urobilinogen is yellow.
False - colorless
T/F: Urobilinogen is mainly excreted by the kidneys.
False - only 2%
Urine urobilinogen (increases/decreases) when there’s total bile duct obstruction.
Decreases/disappears
Urine urobilinogen is increased in which general disease states?
BR overproduction (ex: hemolysis)
Jaundice with no bilirubinuria usually means that the serum bilirubin is (conjugated/unconjugated). Why?
Unconjugated (can’t be excreted in urine); conjugated BR would be excreted by kidney if significant amounts were circulating in serum
DDx for conjugated hyperbiliruminemia.
Mnemonic: BICH
- Bile duct obstruction
- Inherited (Dubin-Johnson, Rotor’s)
- Cholestatic disease
- Hepatitis
Dubin-Johnson follows (X) inheritance pattern and involves point mutation in gene for (Y). Highest incidence in which ethnic group?
X = AR Y = MRP2 protein (nonfunctional)
Iranian Jews
24 y.o. M presents with upper resp tract infection and jaundice. He reports this has happened before when he had the flu. Serum BR is 4 mg/dL and mostly conjugated. Likely diagnosis is (X).
X = Dubin-Johnson Syndrome
In (X) inherited etiology of hyperbilirubinemia, liver tissue is darkly pigmented, often black.
X = Dubin-Johnson Syndrome
DDx for unconjugated hyperbiliruminemia.
- Hemolysis
- Ineffective erythropoeisis
- Neonatal/breast milk jaundice
- Drug-induced
- Inherited (Crigler-Najjar, Gilbert’s)
T/F: Over 90% of newborns have high BR levels with over 50% becoming jaundiced.
True
T/F: Hemolysis usually causes severe elevation of BR (over 10 mg/dL).
False - usually mild between 1-4 mg/dL
Why might ineffective erythropoeisis be a cause for (conjugated/unconjugated) hyperbilirubinemia?
RBC destruction in bone marrow leads to large BR load
Crigler-Najjar Syndrome is inherited in (X) pattern involving (Y) protein.
X = AR Y = UGT (conjugates BR)
Crigler-Najjar Type I: (X) protein is (defective/absent) and therapy involves (Y).
X = UGT
Absent (severe, death by 18 mo)
Y = liver transplant
Crigler-Najjar Type II: (X) protein is (defective/absent) and therapy involves (Y).
X = UGT
Defective (mild form, survival to adulthood)
Y = Phenobarbital therapy (increases expression of UGT)
Patient with Crigler-Najjar Type II presents with jaundice. You would expect urine BRDG to be (low/normal/high).
Normal (high circulating BR is unconjugated)
Gilbert’s Syndrome is condition characterized by (constant/intermittent) (conjugated/unconjugated) hyperbilirubinemia. Which protein involved?
Intermittent (bouts);
unconjugated
UGT (levels either reduced or protein defective with reduced activity)
T/F: Gilbert’s Syndrome patients typically don’t require Rx.
True
