Medicine Marrow Pg No 985-994 (Hepatology)
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Questions and Answers

What is the primary purpose of the FibroScan device?

  • To check liver enzyme levels
  • To assess liver stiffness (correct)
  • To perform liver biopsies
  • To measure liver weight
  • A FibroScan reading of 77.5 kPa indicates nonalcoholic steatohepatitis (NASH).

    False

    Which diagnostic tool is considered the best option for liver diagnosis but is also more expensive than FibroScan?

    MR Elastography

    The FibroScan uses a technique known as __________ elastography.

    <p>transient</p> Signup and view all the answers

    Match the liver conditions with their corresponding interpretations in the chronic setting:

    <p>Not significant = Chronic setting Poor prognosis = Fulminant hepatic failure (FHF) Acute INR ≥ 1.5 = Acute setting</p> Signup and view all the answers

    What level of alkaline phosphatase (ALP) suggests cholestasis?

    <blockquote> <p>560 units/L</p> </blockquote> Signup and view all the answers

    What is the primary precursor of bilirubin?

    <p>Heme substances</p> Signup and view all the answers

    Wilson's disease is associated with increased levels of alkaline phosphatase (ALP).

    <p>False</p> Signup and view all the answers

    Heme oxygenase is one of the enzymes involved in the metabolism of bilirubin.

    <p>True</p> Signup and view all the answers

    How much bilirubin is produced daily in a typical adult?

    <p>300 mg</p> Signup and view all the answers

    List two sources of alkaline phosphatase (ALP) in the human body.

    <p>Liver, Bone</p> Signup and view all the answers

    Intrahepatic cholestasis is often associated with __________ due to bile acid accumulation.

    <p>pruritis</p> Signup and view all the answers

    The production of bilirubin occurs at a rate of ____ mg/kg.

    <p>4</p> Signup and view all the answers

    Match the following markers with their sources:

    <p>ALP = Liver, Bone, Intestine, Kidney, Placenta GGT = Only liver 5' nucleotidase = Liver + Bone Delta bilirubin = Binds to Albumin</p> Signup and view all the answers

    Match the following sites with their relevance to hemoglobin metabolism:

    <p>Reticuloendothelial system = Location of major breakdown of hemoglobin Liver = Site for bilirubin metabolism Bone marrow = Production of red blood cells Spleen = Removal of aged red blood cells</p> Signup and view all the answers

    What is the normal range for total bilirubin levels in mg/dL?

    <p>1-1.3</p> Signup and view all the answers

    High levels of urobilinogen in urine indicate obstruction of the biliary tract.

    <p>False</p> Signup and view all the answers

    What is the primary substance excreted in feces resulting from deconjugation of bilirubin?

    <p>Stercobilinogen</p> Signup and view all the answers

    The condition _____ may progress to cirrhosis with portal hypertension.

    <p>chronic hepatitis</p> Signup and view all the answers

    Match the following aspects of liver disease progression with their associated complications:

    <p>Acute Hepatitis = Chronic hepatitis Chronic hepatitis = Cirrhosis Cirrhosis = Functional failure</p> Signup and view all the answers

    Which of the following drugs is associated with Bland cholestasis?

    <p>Steroids</p> Signup and view all the answers

    Cholestatic hepatitis can be caused by NSAIDs.

    <p>True</p> Signup and view all the answers

    What condition is associated with Amoxiclav?

    <p>Vanishing bile duct syndrome</p> Signup and view all the answers

    Normal albumin levels in the blood range from _____ g/dL.

    <p>3.5–5.5</p> Signup and view all the answers

    Match the following drugs with their associated liver conditions:

    <p>Chlorpromazine = Cholestatic hepatitis Allopurinol = Granulomatous hepatitis ACE (-) = Vanishing bile duct syndrome Estrogens = Bland cholestasis</p> Signup and view all the answers

    Which of the following viruses is most common in children?

    <p>HAV</p> Signup and view all the answers

    AST levels are always higher than ALT in chronic alcoholic liver disease.

    <p>True</p> Signup and view all the answers

    What enzyme level is indicative of alcoholic liver disease?

    <p>300 - 500 U/ltr</p> Signup and view all the answers

    The condition where AST is greater than ALT at levels exceeding 1000 U/ltr is known as __________.

    <p>acute on chronic alcoholic liver disease</p> Signup and view all the answers

    Match the liver conditions with their respective enzyme ratio:

    <p>Alcoholic hepatitis = AST &gt; ALT (2:1) Definitive Alcoholic hepatitis = AST &gt; ALT (3:1) Acute on chronic liver disease = AST &gt; ALT (&gt;1000 U/ltr) Mild chronic hepatitis = Normal or slight elevation</p> Signup and view all the answers

    Which of the following is the most common virus causing acute hepatitis in children?

    <p>Hepatitis A (HAV)</p> Signup and view all the answers

    Hepatitis E is primarily transmitted through feco-oral routes.

    <p>True</p> Signup and view all the answers

    Name one autoimmune cause of acute hepatitis.

    <p>Autoimmune hepatitis</p> Signup and view all the answers

    The incubation period for Hepatitis A (HAV) is approximately ____ days.

    <p>30</p> Signup and view all the answers

    Match the following hepatitis viruses with their corresponding family:

    <p>Hepatitis A (HAV) = Picornaviridae Hepatitis E (HEV) = Calcivirus Hepatitis B (HBV) = Hepadnaviridae Hepatitis D (HDV) = Defective virus</p> Signup and view all the answers

    What is the recommended preventive measure for Hepatitis A prior to travel?

    <p>HAVRIX 1 mL IM in 2 doses, 6-12 months apart</p> Signup and view all the answers

    Hepatitis E has a higher incidence of complications during pregnancy compared to Hepatitis A.

    <p>True</p> Signup and view all the answers

    What constitutes Acute Liver Failure (ALF)?

    <p>Acute hepatitis, encephalopathy, and coagulopathy without pre-existing liver disease.</p> Signup and view all the answers

    The typical duration for Hepatitis A infection is _____ weeks.

    <p>8</p> Signup and view all the answers

    Match the following conditions with their associated characteristics:

    <p>Hepatitis A = Duration: 8 weeks, Treatment: Conservative Hepatitis E = Duration: 12 weeks, 1-2% incidence Acute Liver Failure = Characterized by encephalopathy and coagulopathy Pregnancy complications = 20% for both HAV and HEV</p> Signup and view all the answers

    What type of hyperbilirubinemia is characterized by indirect bilirubin making up 85% or more of total bilirubin?

    <p>Indirect Hyperbilirubinemia</p> Signup and view all the answers

    Gilbert Syndrome results in total absence of UDP-Glucuronosyltransferase activity.

    <p>False</p> Signup and view all the answers

    What condition is indicative of mixed hyperbilirubinemia in conjunction with transaminitis?

    <p>Crigler-Najjar Syndrome</p> Signup and view all the answers

    Direct hyperbilirubinemia occurs when direct bilirubin constitutes ______% or more of total bilirubin.

    <p>50</p> Signup and view all the answers

    Match the following syndromes with their characteristics:

    <p>Gilbert Syndrome = Partial deficiency of UDP-Glucuronosyltransferase Crigler-Najjar Syndrome I = Complete absence of UDP-Glucuronosyltransferase activity Crigler-Najjar Syndrome II = Reduced UDP-Glucuronosyltransferase activity</p> Signup and view all the answers

    What is the primary function of the canalicular membrane in hepatocytes?

    <p>Excretion of conjugated bile acids</p> Signup and view all the answers

    The sinusoidal membrane is involved in the activation of stellate cells.

    <p>False</p> Signup and view all the answers

    Which syndrome is associated with defects in the canalicular membrane of hepatocytes?

    <p>Dubin-Johnson syndrome</p> Signup and view all the answers

    The space between sinusoids and hepatocytes is known as the __________.

    <p>Space of Disse</p> Signup and view all the answers

    Match the liver disorders with their respective site and affected cell type:

    <p>Hepatic vein thrombosis = Vascular - hepatic vessels/portal vein Primary biliary cirrhosis = Biliary - cholangiocyte Cirrhosis = Parenchymal - hepatocyte &amp; sinusoids Cirrhotic pathology = Vascular - stellate/Ito cells</p> Signup and view all the answers

    What condition arises due to the activation of myofibroblasts in the liver?

    <p>Cirrhosis</p> Signup and view all the answers

    Vitamin A is stored in stellate cells located in the space of Disse.

    <p>True</p> Signup and view all the answers

    What protein is contained in the canalicular membrane of hepatocytes?

    <p>MRP-a protein</p> Signup and view all the answers

    Study Notes

    FibroScan

    • Measures liver stiffness
    • Non-invasive method to differentiate between NASH and cirrhosis
    • Reading of 77.5 kPa indicates cirrhosis
    • Transient elastography device
    • MR Elastography is another tool used
    • Considered the best diagnostic tool but more expensive
    • Used to confirm FibroScan results

    Alkaline Phosphatase (ALP)

    • Indicates cholestasis when levels are > 4x normal (>560 units/L)
    • Normal range: 40-140 units/L
    • Decreased levels can indicate Wilson's disease
    • Major source: Liver - canalicular membrane of hepatocyte
    • Other sources include bone, intestine, kidney, and placenta

    Cholestasis

    • Associated with: Pruritis (due to bile acid accumulation)
    • Jaundice may or may not be present
    • Causes:
      • Drugs
      • Cholangitis
      • Sarcoid
      • Primary biliary cirrhosis
      • Primary sclerosing cholangitis
      • Sepsis

    Conjugated Hyperbilirubinemia

    • Hyperbilirubinemia: >50% direct bilirubin
    • ALP > 4 times normal + GGT significantly elevated

    Bilirubin

    Features

    • Production rate: 4mg/kg (300mg/day)
    • Precursor: Heme substances
    • Metabolizing enzymes: Heme Oxygenase (HOX) and Biliverdin reductase

    Hemoglobin (80%)

    • Site: Reticuloendothelial system, liver, bone marrow
    Excretion
    • Pathway: Bile → Biliary pathway → Small intestine
    • Urobilinogen in urine:
      • Traces: Normal
      • High: Extravascular hemolysis
      • Absent: Obstruction of biliary tract
    • Ileocecal junction & Colon: Degradation by colonic bacteria
    • Deconjugation:
      • 80%: Excreted in feces (Stercobilinogen)
      • 20%: Via enterohepatic circulation → Small amount → Systemic Circulation

    Liver Function Test

    • Total Bilirubin: 1-1.3 mg/dL
    • Unconjugated/Indirect Bilirubin: 0.2-0.9 mg/dL
    • Conjugated/Direct Bilirubin: 0-0.3 mg/dL
    • Estimated by: HPLC (High-performance liquid chromatography)
    • Note: Liver diseases, Hepatic parenchymal disorders, Vascular disorders, Biliary disorders

    Progression of Liver Disease

    • Acute Hepatitis → may progress → Chronic hepatitis → may progress → Cirrhosis with:
      • Portal hypertension
      • Hepatocellular carcinoma (HCC)
      • Functional failure

    Drugs causing cholestasis

    Bland cholestasis

    • Steroids
    • Estrogens

    Cholestatic hepatitis

    • NSAIDs
    • Azathioprine
    • Chlorpromazine

    Granulomatous hepatitis

    • Allopurinol
    • Carbamazepine
    • Procainamide

    Vanishing bile duct syndrome

    • Amoxiclav (Amoxicillin + clavulanate)
    • Macrolides
    • ACE inhibitors (-)

    Other Investigations

    Synthetic Functions of Liver

    Albumin
    • Normal levels: 3.5–5.5 g/dL
    • Hypoalbuminemia: May indicate liver disease

    Hepatocyte Membranes

    • Contiguous Membrane:
      • Gap junctions between hepatocytes
      • Contains MRP-a protein
    • Canalicular Membrane:
      • Gene: ABCCa
      • Function: Excretion of conjugated bile acids (bile salts)
      • Defect: Dubin-Johnson syndrome
    • Sinusoidal/Basolateral Membrane:
      • Cells: Stellate/Ito cells and lipocytes
      • Location: Space of Disse
      • Function: Storage of vitamin A
      • Pathology: Cirrhotic pathology: activation of myofibroblasts → cirrhosis. TGF-β releases

    Liver Disorders

    Site Vessel/Cell Disorder
    Vascular Vessel: hepatic vessels/portal vein etc. Hepatic vein thrombosis (Budd-Chiari Syndrome)
    Parenchymal Hepatocyte & sinusoids Any disease leading to cirrhosis
    Biliary Cholangiocyte Primary biliary cirrhosis, primary sclerosing cholangitis

    Basic Physiology of Liver

    Causes of Liver Disease

    • Virus (most common):
      • HAV (common in children)
      • HEV (common in adults)
    • Drug/toxin induced
    • Ischemic hepatitis
    • Alcohol (Values: 300 - 500 u/ltr)
      • Note: Severe acute elevations also seen in Acute bile duct obstruction (>1000 U/Ltr).

    Alcoholic Liver Disease

    • Enzyme level: 300 - 500 U/ltr
    • AST > ALT: ALT requires more amount of PLP.
      • 2:1: Almost always alcoholic hepatitis.
      • 3:1: Definitive Alcoholic hepatitis.
    • Acute on chronic alcoholic liver disease: AST > ALT (values >1000 u/ltr).

    Chronic Hepatitis

    • Mild elevation: Indicates ongoing liver inflammation

    Hepatology

    Hepatitis A (HAV)

    • Rare (1 in 2 lakhs)
    • Duration: 8 weeks
    • Treatment:
      • Conservative (fluid and glucose repletion)
      • 150 ml 10% Dextrose
    • Complications:
      • 1-2% cases
      • 20% in pregnancy
      • 12 weeks
      • Conservative treatment
      • Long standing cholestasis
      • Steroids
    • Prevention:
      • HAVRIX 1 mL IM in 2 doses, 6-12 months apart.
      • Pre-exposure: at least 2 weeks of travel.
      • Post-exposure: within 4 weeks.
      • No vaccine

    Hepatitis E (HEV)

    • 1-2%
    • 20% in pregnancy
    • Duration: 12 weeks

    Note:

    • If ALT/AST, AST > ALT > 1000: underlying alcoholic d/s.
    • If MELD score: 300-500: alcoholic hepatitis.
    • Lab tests: INR, s.Bilirubin, s.Creatinine

    Acute Liver Failure (ALF)

    • Acute hepatitis + encephalopathy (cerebral edema) + coagulopathy (INR ≥ 1.5) without any pre-existing liver disease.
    • Onset:
      • Fulminant (hyperacute): Rapid progression (days to weeks)
      • Subfulminant: Slow onset (weeks)

    Hyperbilirubinemia

    • Indirect Hyperbilirubinemia (unconjugated hyperbilirubinemia):

      • Indirect bilirubin: ≥ 85% of total bilirubin
    • Mixed Hyperbilirubinemia/Hepatic jaundice:

      • Direct bilirubin: 15-50% of total
    • Direct Hyperbilirubinemia (Conjugated hyperbilirubinemia):

      • ≥ 50% total Bilirubin
      • Cholestasis

    Inherited causes of Hyperbilirubinemia:

    • Gilbert Syndrome: Partial deficiency of UDP-Glucuronosyltransferase (only 30% activity)
    • Crigler-Najjar Syndrome I/II: Reduced UDP-Glucuronosyltransferase activity
    • Rotor Syndrome: Defective transport of bilirubin into canaliculi
    • Dubin-Johnson Syndrome: Defective transport of bilirubin into bile. Leads to pigment accumulation in the liver

    Acute Hepatitis and Acute Liver Failure

    Acute Hepatitis

    • Recovery (most common)
    • Chronic Hepatitis
    • Fulminant Hepatic Failure (rare)

    Fulminant Hepatic Failure

    • Portal Hypertension (Portal HTN)
    • Hepatocellular Carcinoma (HCC)
    • Liver Failure

    Acute Hepatitis Causes

    • Viral:
      • HAV (most common in children)
      • HEV (most common in adults)
      • HBV
      • HBV + HDV (coinfection)
    • Drugs:
      • Paracetamol
      • ATT
    • Toxins:
      • Rat poison (Yellow Phosphorus)
      • Mushroom
      • Alcohol
    • Others:
      • Autoimmune hepatitis
      • Wilson's disease
      • AFLP (Acute Fatty Liver of Pregnancy)
      • Budd Chiari syndrome

    Hepatitis A (HAV) vs Hepatitis E (HEV)

    Feature HAV HEV
    Virus Picornaviridae family, SS-RNA Calcivirus family, RNA
    Mode of transmission Feco-oral, Sexual/parenteral Feco-oral >> vertical
    Incubation period 30 days 40 days
    Heat sensitivity Sensitive (>85°C)
    Features
    - Prodromal phase (2-3 days)
    - Anorexia, nausea, vomiting
    - Malaise, low-grade fever, jaundice
    Cholestatic Hepatitis
    - Extrahepatic features Tender hepatomegaly (max 2 cm), rash/arthralgia (most common)
    - Progression of chronicity Rare Not seen
    - Lab investigations ↑ALT, AST, ↑S.Bilirubin (mixed pattern), Anti HAV IgM (+) ↑ ALT, AST, ↑ S.Bilirubin (conjugated), Anti HEV IgM (+) (upto 4 months)

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    Description

    Test your knowledge on key diagnostic tools and markers for liver diseases. This quiz covers important topics such as FibroScan, alkaline phosphatase levels, and cholestasis. Assess your understanding of liver conditions and their indicators to better grasp their clinical implications.

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