Liver - Clinical Chemistry

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Primary functions of liver synthesis, metabolism, detoxification, excretion
total serum protein, albumin, prealbumin, PT/INR (clotting pro-
Examples of liver function tests and what they are testing for teins, prothrombin time), bilirubin (red blood cell metabolism),
ammonia, enzymes (ALP, 5NT, GGTP, AST, ALT, LDH)
- albumin: synthesized by liver, half life of 20 days, low values
due to decreased serum synthesis, decreased in those with liver
Compare albumin vs. prealbumin
disease, decreased in those with hepatitis
- prealbumin: half life of 2 days, protein nutrition
- cholestatic: obstruction of bile duct or inhibition of bilirubin and
What are the two types of liver disease based on cellular physiol-
bile synthesis or secretion
ogy?
- hepatocellular: damage or inflammation of liver cells
alkaline phosphatase (ALP), 5-nucleotidase (5-NT), gamma-glu-
What are the indicators of cholestatic liver disease?
tamyl transpeptidase (GGTP)
- diagnoses hepatobiliary disorders
How is ALP interpreted to suggest a cholestatic disorder? - bile accumulation causes liver cells to synthesize more ALP and
leaks into serum
Why are additional tests needed to confirm source of ALP in-
needed to confirm source of ALP increase, either GGTP or 5-NT
crease?
What conditions other than liver disease can cause an increase
skeletal disease, pregnancy
ALP?
- ratio of GGTP/ALP > 2.5
What biochemical changes can be used to assess chronic alcohol
- high AST
use or alcoholic liver disease?
- increased ALT
What are the indicators of hepatocellular injury? AST, ALT, LDH
- found in liver, heart, skeletal muscle, kidneys, and pancreas
- elevated levels indicate hepatitis or alcoholic cirrhosis
- 20: acute viral hepatitis, drug induced hepatic injugry
AST and levels
- 10-20: severe infectious mononucleosis, alcoholic cirrhosis
- 5-10: chronic hepatitis
- 2.5: hepatic tumors or unexplained (vigorous exercise)
- found in liver, heart, and muscles
- more specific than AST
- high: viral or drug induced hepatitis
ALT and levels - moderate: chronic hepatitis, early viral hepatitis, hepatic conges-
tion due to heart failure
- slight to moderate: active cirrhosis, drug induced or alcoholic
hepatitis
Compare ALT to AST in terms of specificity toward liver disease ALT is more specific to the liver than AST
- skeletal muscle, liver, kidney, and heart (not specific)
Is LDH specific to the liver? What can be done to distinguish the - MI: LDH1>LDH2
origin of LDH increase? - increase of LCH2 and LCH3 indicate lung injury
- LDH5>LDH4 suggestive of liver disease
- PT normalizes after vitamin K: malabsorption, malnutrition, an-
tibiotics
How to interpret PT/INR values in terms of blood coagulation
- PT remains prolonged after vitamin K: liver failure
function. What's the relationship between PT and INR?
- PT: prothrombin time
- INR: international normalized ratio
- unconjugated = indirect, insoluble, requires dissolving agents to
Understand the generation and differences between unconjugat-
be detected
ed and conjugated bilirubin (indirect vs. direct)?
- conjugated = direct, soluble, detected by van der Bergh reaction
- unconjugated: hemolytic anemia, Gilbert's syndrome
What are the causes of increased bilirubin? - conjugated: bile duct obstruction, hepatitis, drugs
- both: hepatitis
How to interpret increase of unconjugated vs. conjugated bilirubin
in context of ALT, AST, GGTP.
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What are the potential causes of liver disease?
allopurinol, antibiotics, cardiovascular, carbamazepine, hormonal
What drugs can cause cholestasis?
agents
What drugs can cause hepatocellular injury?
What are the common features of alcoholic liver disease?
What's the main toxic metabolite of alcohol?
Why does alcohol use lead to fatty liver?
What are the biochemical markers for alcoholic liver disease?
- inflammation of the liver with accompanying liver cell damage or
cell death
What's hepatitis? What can cause hepatitis?
- causes: viral infection, drug or chemical induced, metabolic
disorder, autoimmune reaction
What are the common biochemical changes in hepatitis?
What are the main pathway of infection/spreading for HAV, HBV,
and HCV?
How are HAV, HBV, and HCV detected?
Understand the meaning of hepatitis B markers' abbreviation
Know how to distinguish successful HBV vaccination from previ-
ous infection, active infection, and resolving infection
Know the relationship between HCV and liver cirrhosis. How is
HCV treated?
- 1) direct (N) indirect (++) ALT, AST, GGTP (N)
- 2) direct (++) indirect (N) ALT, AST, GGTP (N)
- 3) direct (+) indirect (++) ALT, AST, GGTP (++)
- drug-induced
- alcohol
- viruses
- genetic
- cancer
acetaminophen, allopurinol, amiodarone, antiseptic agents, an-
timicrobial agents, cisplatin, methotrexate, glyburide, trazodone,
phenothiazines, NSAIDs, statins
- major cause of liver disease
- risk dose is 80 grams of alcohol
- daily drinking is riskier than intermittent drinking
- women are at greater risk than men
Acetaldehyde
accumulation of cholesterol or triglycerides
- AST:ALT > 2
- high concentrations of GGTP with GGTP:ALP > 2.5
- early disease is reversible with cessation of alcohol intake
- increased bilirubin
- decreased serum albumin
- increase in gamma globulin
- moderate increase in ALP
- increase up to 10X in ALT and AST
- GGTP increase
- HAV: spread through contact with infected persons
- HBV: transmitted through blood transfusions, needle sharing,
sexual encounters, placenta
- HCV: spread parenterally, vertically, and sexually
- HAV: antibodies to the virus that are produced by the patient,
anti-HAV antibodies
- HBV: immunoassay or PCR
- HCV: ELISA and PCR
HBsAg: hepatitis B surface antigen
HBeAg: hepatitis B e antigen
Anti-HBc IgM: IgM antibody to hepatitis B core antigen
Anti-HBc: antibody to hepatitis B core antigen
Anti-HBe: antibody to hepatitis B e antigen
Anti-HBs: antibody to hepatitis B surface antigen
- previous infection (+) anti-HBs and anti-HBc
- active infection (+) HBs Ag and anti-HBc
- resolving infection/vaccination (+) anti HBs
- many with HCV also have been diagnosed with cirrhosis
- interferon-ribavirin combination, protease inhibitors, RNA poly-
merase inhibitors, and viral protein inhibitor

Which of the following substances is administered to a patient

with a long prothrombin time to determine if the cause is liver
C
malfunction or malnutrition?

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 Liver - Clinical Chemistry
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A) Ascorbic acid
B) Vitamin E
C) Vitamin K
D) Warfarin
Which of the following is not increased during hepatitis infection?

A) Serum albumin
B) Bilrubin
A
C) Gamma globulin
D) ALT
E) AST
F) GGTP
Unconjugated bilirubin (indirect) is insoluble in aqueous con-
ditions and cannot be directly detected by the van der Bergh
reaction. Conjugated bilirubin is formed in the liver by UFT1A1
catalyzed glucuronidation and can be detected by the van der True
Bergh reaction.

True or False
Which of the following is indicative of alcoholic liver disease?

A) AST:ALT > 2 and/or GGTP:ALP > 2.5

A
B) SCr > 3 mg/dL
C) AST > 10 x ULN
D) BUN:SCr > 20
Elevated ALP and normal 5-NT means the problem is probably a
non hepatic etiology
True
True or False
If a patient's total bilirubin is high, which of the following lab tests
would be consistent with the bilirubin being high due to hemolysis
rather than liver dysfunction?
B
A) ALT
B) indirect bilirubin
C) ALP
D) GGTP
Which of the below is considered the primary toxin generated
by the liver following alcohol ingestion that is believed to be the
causes of alcoholic liver disease?

A) Acetaldehyde A
B) Lactic acid
C) Ascorbic acid
D) Methanol
E) Glutathione
Elevated ALP and normal 5-NT means the problem is probably a
non hepatic etiology.
True
True or False
Which of the following proteins has a half-life of approximately 20
days and decreased concentrations in serum are indicative of liver
disease?

A) Alkaline phosphatase E
B) Prealbumin
C) Aspartate aminotransferase
D) Prothrombin
E) Albumine

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Which markers indicated late seroconversion in patients with
chronic HBV?

A) - HBsAg and + anti-HBs B

B) - HBeAg and + anti-HBe
C) + HBeAg and + anti-HBc
D) + HBeAg and + HBsAg
Which test is positive for healthcare workers after a successful
HBV vaccination?

A) HBsAg
B) Anti-HBs B
C) Anti-HBs and anti-HBc
D) HBeAg
E) Anti-HBe and anti-HBc
F) HBcAg

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