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Questions and Answers
What does an R value of ≥5 indicate in liver function tests?
Which enzyme is primarily found in the liver and is a marker for liver function?
Which condition is associated with an AST/ALT ratio greater than 2?
What is the half-life of ALT in liver function tests?
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In which scenario is the De Ritis ratio expected to be normal or less than 1?
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What does a De Ritis ratio greater than 1 generally indicate?
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What is true regarding the specificity of AST compared to ALT for liver disease diagnosis?
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What common condition may lead to a significant increase in AST levels due to mitochondrial damage?
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What is one unique characteristic of the liver compared to other organs?
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Which of the following is NOT a metabolic function of the liver?
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What role does bile play in digestion?
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Which of the following substances does the liver convert into urea?
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Which of the following vitamins is NOT stored in the liver?
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What type of proteins are primarily synthesized by the liver?
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Which of the following is a role of the liver in cholesterol management?
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What is the primary function of detoxification in the liver?
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Which liver biochemical test primarily reflects the synthetic function of the liver?
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What is a limitation of liver function tests (LFTs)?
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Which condition is characterized by elevated levels of ALT and AST?
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In which liver syndrome would you expect an increase in alkaline phosphatase (ALP)?
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What does an increased prothrombin time typically indicate in liver function tests?
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Which liver enzyme is primarily located in the mitochondria and cytosol of hepatocytes?
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What type of liver injury does a high R value indicate?
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Which of the following is NOT typically a marker of liver dysfunction?
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What condition is most likely to cause the highest elevations in AST levels?
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Which of the following is NOT a common cause of severe elevations in aminotransferase levels?
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Which evaluation test is used specifically to look for evidence of vascular occlusion in patients with elevated aminotransferases?
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What is the main purpose of measuring acetaminophen levels in patients with elevated aminotransferases?
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Which of the following conditions is associated with acute fatty liver of pregnancy?
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Which of these is a common method to evaluate for Wilson disease in patients with elevated aminotransferases?
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Which of the following is NOT typically evaluated in patients suspected of acute viral hepatitis?
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What is the significance of finding more than 15 times the upper limit of normal in aminotransferase levels?
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Which of the following is a symptom associated with muscle disorders leading to elevated aminotransferases?
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Which of the following viruses is NOT typically included when assessing serologies for acute viral hepatitis?
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Study Notes
Liver Characteristics
- The liver is the largest gland in the body, weighing approximately 1.5 kg.
- Located under the diaphragm, within the rib cage in the upper right quadrant of the abdomen.
- The only human organ that can self-regenerate.
- Performs over 500 functions.
Liver Functions
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Metabolic:
- Carbohydrates, lipids, and protein metabolism (glucose to glycogen, amino acids to ammonia and urea, fatty acids to energy, lipids to GNG).
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Excretion:
- Synthesis of bile in the liver emulsifies lipids and fat-soluble vitamins for digestion, preventing cholesterol precipitation in the gallbladder.
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Synthetic:
- Produces and regulates triglycerides, phospholipids, lipoproteins, and cholesterol.
- Synthesizes proteins (100% albumin, 75-90% α globulins, 50% β globulins, Ƴ globulins (RES)).
- Converts proteins to non-essential amino acids and functional proteins for clotting, ferritin for iron transport, lipoprotein for cholesterol transport, albumin for oncotic pressure, and globulins for immune function.
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Detoxification:
- Converts ammonia to urea.
- Detoxifies alcohol, synthetic and natural drugs, steroidal and non-steroidal hormones (corticosteroids, testosterone, progesterone, estrogen, thyroid hormones, insulin, growth hormones).
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Storage:
- Stores fat-soluble Vitamins (A, D, E, K), B12, and minerals like Zn, Fe, Cu, Mg.
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Immune:
- Synthesizes immunoglobins in RES, Kupffer cells.
Liver Biochemical Tests (LBTs)
- Used to screen for liver disease, differentiate types of liver disease, assess severity and prognosis, monitor response to treatment.
- LFTs is a misleading term as it includes tests reflecting liver injury, not liver function.
- Liver function is assessed by serum albumin, bilirubin, and prothrombin time.
- Abnormal LBT values can be caused by conditions unrelated to the liver.
- Tests may be normal in patients with advanced liver disease.
LBTs Classification by Liver Function
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Synthetic Function:
- Plasma proteins (albumin, globulins), prothrombin time, INR.
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Detoxification:
- Ammonia
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Excretion:
- Serum bilirubin, urine bilirubin, urine and fecal urobilinogen.
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Storage Function:
- Vitamins A, D, E, K, B12.
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Metabolic Function:
- Serum proteins, cholesterol.
- Liver Enzymes (AST, ALT, ALP, LDH, Ƴ-GT):
Location of Enzymes in Hepatocytes
- AST: Mitochondria, cytosol.
- ALT: Cytosol.
- ALP: Canalicular surface.
- Ƴ-GT: Canalicular surface, microsomes.
- LDH: Cytosol.
Liver Syndrome Classification
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Hepatocellular Syndrome:
- Elevated AST (aspartate aminotransferase)
- Elevated ALT (alanine aminotransferase)
- Elevated LDH
- Elevated Iron, ferritin
- Elevated B12
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Cholestatic Syndrome:
- Elevated ALP (alkaline phosphatase)
- Elevated Ƴ-GT (gamma-glutamyl transpeptidase)
- Elevated bilirubin
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Liver Failure Syndrome:
- Elevated bilirubin
- Decreased albumin
- Elevated prothrombin time.
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Inflammatory Syndrome:
- Elevated serum proteins, globulins, Ƴ-globulins, IgA, IgM, IgG.
- Positive antibodies (anti-DNR, ANA, SMA, LKM-1, AMA, SLA).
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Infiltrative Syndrome:
- Elevated ALP, Ƴ-GT, tumor markers (Ca19.9, αFTP).
R Value for Liver Injury Type
- Determines type of liver injury (hepatocellular vs. cholestatic) in patients with elevated aminotransferases and alkaline phosphatase.
- R value = (ALT ÷ ULN ALT) / (ALP ÷ ULN ALP)
- R value interpretation:
- ≥5: Hepatocellular injury
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2 to 5: Cholestatic injury
AST, ALT Location and Clearance
- ALT found primarily in the liver.
- AST is present in liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes, and erythrocytes.
- AST is less specific for liver disease than ALT.
- Hepatocyte membrane damage increases permeability, releasing enzymes even without necrosis.
- Major site of transaminase clearance is the hepatic sinusoidal cell (RES).
- Elimination half-life for AST is 17 hours, ALT 47 hours.
De Ritis Ratio (AST/ALT)
- Normal range ≤1.
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“Inflammatory” type: ≤1
- Viral hepatitis, NAFLD.
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“Necrotic” type: >2
- Alcoholic hepatitis, fulminant Wilson's disease, drugs, toxins, non-hepatic causes, ischemic hepatitis.
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Liver Cirrhosis: >1
- Alcoholic hepatitis has higher AST due to mitochondrial damage and reduced ALT synthesis due to B6 deficiency.
- Chronic viral hepatitis, alcoholism, NAFLD, and an elevated AST/ALT ratio are associated with long-term complications including fibrosis and cirrhosis.
Alcoholic/Nonalcoholic Fatty Liver Disease Score (ANI Score )
- Uses AST, ALT, gender, weight, and MCV to determine the likelihood of alcoholic or nonalcoholic fatty liver disease.
- Available on the Mayo Clinic website.
Causes of Severe Elevations in Aminotransferase Levels
- Acetaminophen (paracetamol) toxicity
- Idiosyncratic drug reactions
- Acute viral hepatitis (hepatitis A, B, C, D, E, herpes simplex virus, varicella zoster virus, EBBV, CMV, other viral infections, an acute exacerbation of chronic viral hepatitis (hepatitis B)
- Alcoholic hepatitis
- Autoimmune hepatitis (elevations above 15 times the upper limit of normal)
- Wilson disease
- Ischemic hepatitis
- Budd-Chiari syndrome
- Sinusoidal obstruction syndrome (veno-occlusive disease)
- HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome
- Acute fatty liver of pregnancy
- Malignant infiltration (breast cancer, small cell lung cancer, lymphoma, melanoma, myeloma)
- Partial hepatectomy
- Toxin exposure (mushroom poisoning)
- Sepsis
- Heat stroke
- Muscle disorders (acquired muscle disorders, seizures, heavy exercise)
Evaluation of Markedly Elevated Aminotransferases (1)
- Acetaminophen level and toxicology screen
- Acute viral hepatitis serologies (IgM anti-hepatitis A virus, Hepatitis B surface antigen (HBsAg), IgM anti-hepatitis B core antigen (anti-HBc), antibody to HBsAg, Anti-hepatitis C virus antibody (HCV), hepatitis C viral RNA, anti-herpes simplex virus antibodies, anti-varicella zoster antibodies, anti-CMV antibodies, CMV IgM, Epstein-Barr IgM)
- Serum pregnancy test in women of childbearing potential
- Autoimmune markers (antinuclear antibodies, anti-smooth muscle antibodies, anti-liver/kidney microsomal antibodies type 1, IgG)
- Transabdominal ultrasonography with Doppler imaging for vascular occlusion (Budd-Chiari syndrome)
Evaluation of Markedly Elevated Aminotransferases (2)
-
Additional Tests:
- Ceruloplasmin level and urinary copper quantitation for Wilson disease
- Hepatitis D virus antibodies for patients with acute or chronic hepatitis B
- Hepatitis E virus antibodies for patients from endemic areas, especially pregnant patients (due to high rates of liver failure in pregnant women with hepatitis E)
- Urinalysis for proteinuria in pregnant women
- Serum creatinine kinase or aldolase for patients with muscle disorders.
- If testing negative, liver biopsy is recommended, especially if elevations fail to decline, suggesting developing acute liver failure.
- If the elevation is due to a clear cause and resolves with treatment, no further investigation is required.
- If the elevation is unexplained, further investigation is needed to determine the underlying cause.
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Description
Test your knowledge on the liver's unique characteristics and vital functions in the human body. This quiz covers aspects of liver metabolism, excretion, and synthetic roles that underscore its importance for overall health. Gain insights into how this remarkable organ maintains bodily functions and contributes to various metabolic processes.
