Podcast
Questions and Answers
What does the International Normalized Ratio (INR) primarily indicate in patients on warfarin therapy?
What does the International Normalized Ratio (INR) primarily indicate in patients on warfarin therapy?
Which condition is NOT accurately identified by Transient Elastography (TE)?
Which condition is NOT accurately identified by Transient Elastography (TE)?
In cholestasis, ultrasonography is primarily used to identify which of the following?
In cholestasis, ultrasonography is primarily used to identify which of the following?
The primary use of ultrasound with Doppler imaging in liver assessments is to determine what?
The primary use of ultrasound with Doppler imaging in liver assessments is to determine what?
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What metabolic process removes ammonia from the body?
What metabolic process removes ammonia from the body?
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What is a common symptom of hepatic encephalopathy related to sleep?
What is a common symptom of hepatic encephalopathy related to sleep?
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Which of the following factors can precipitate hepatic encephalopathy?
Which of the following factors can precipitate hepatic encephalopathy?
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Which skin disorder is characterized by slate-gray pigmentation?
Which skin disorder is characterized by slate-gray pigmentation?
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What is one of the triad symptoms of hepatopulmonary syndrome?
What is one of the triad symptoms of hepatopulmonary syndrome?
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Which laboratory test is used to determine if alkaline phosphatase elevations are due to liver disease?
Which laboratory test is used to determine if alkaline phosphatase elevations are due to liver disease?
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What collection of laboratory findings is characteristic of Wilson's disease?
What collection of laboratory findings is characteristic of Wilson's disease?
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What is the gold standard for evaluating chronic liver disease?
What is the gold standard for evaluating chronic liver disease?
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What condition is indicated by the presence of fetor hepaticus?
What condition is indicated by the presence of fetor hepaticus?
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What is the primary function of hepatocytes concerning glucose management?
What is the primary function of hepatocytes concerning glucose management?
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Which liver disease category is characterized by inflammation and necrosis of liver cells?
Which liver disease category is characterized by inflammation and necrosis of liver cells?
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Which of the following tests measures liver function related to protein synthesis?
Which of the following tests measures liver function related to protein synthesis?
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What are Kupffer cells primarily responsible for in the liver?
What are Kupffer cells primarily responsible for in the liver?
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In which zone of the liver acinus do hepatocytes primarily reside?
In which zone of the liver acinus do hepatocytes primarily reside?
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Which condition indicates a cholestatic liver disease?
Which condition indicates a cholestatic liver disease?
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What role do Stellate cells play when not activated?
What role do Stellate cells play when not activated?
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Which liver function test specifically evaluates hepatic excretion?
Which liver function test specifically evaluates hepatic excretion?
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Study Notes
Liver Function Evaluation
- The liver is the largest organ/gland in the body, weighing 1-1.5 kg.
- The hepatic artery provides 20% of the blood flow, and the portal vein brings in 80% of nutrient-rich blood.
Portal Triad
- Branches of the hepatic artery, portal vein, and a bile duct tributary.
Liver Cells
- Hepatocytes make up 2/3 of the liver's mass.
- Kupffer cells are part of the reticuloendothelial system (RES).
- Stellate cells (Ito cells) store fat.
Liver Acinus
- A physiologic unit in the liver.
- Consists of 3 zones.
- Zone 1 receives blood from the hepatic artery and portal vein, and hepatocytes in this zone are first exposed to the blood.
- Zone 2 has hepatocytes in the middle.
- Zone 3 has hepatocytes close to the terminal hepatic veins.
Kupffer Cells
- Located within the sinusoidal vascular space
- The largest group of fixed macrophages in the body
Stellate Cells
- Located in the space of Disse
- Not prominent unless activated, in which case they create collagen and matrix.
Hepatocyte Functions
- Synthesize proteins like albumin and coagulation factors.
- Produce bile.
- Regulate nutrients such as glucose, glycogen, lipids, cholesterol, and amino acids.
- Metabolize and conjugate lipophilic compounds (bilirubin, anions, cations, drugs).
Liver Function Tests
- Measure hepatic conjugation and excretion of bilirubin.
- Measure protein synthesis using serum albumin level and prothrombin time.
Liver Diseases Category
- Hepatocellular: Inflammation and necrosis (viral hepatitis, alcoholic liver disease).
- Cholestatic: Inhibition of bile flow (gallstones, malignant obstruction, primary biliary cholangitis, drug-induced liver diseases).
- Mixed: A combination of hepatocellular and cholestatic injury.
Clinical History: Signs and Symptoms
- Common: Fatigue (most common and characteristic symptom), weakness, poor appetite
- Less common: Nausea, malaise, light stools, pruritus, dark urine, abdominal pain
- Other: diarrhea is uncommon except for severe jaundice, pain from stretching/irritation of Glisson's capsule (rich in nerve endings), severe pain with gallbladder disease, liver abscess, veno-occlusive disease; itching with acute and chronic liver disease (cholestatic types like primary biliary cholangitis and sclerosing cholangitis) are other symptoms.
- Jaundice: Hallmark symptom, most reliable marker of severity
Liver Disease: Familial Causes
- Wilson disease
- Hemochromatosis
- α1-antitrypsin deficiency
- Intrahepatic cholestasis
Physical Examination
- General: Icterus (jaundice), hepatic tenderness, splenomegaly, spider angiomata, palmar erythema
- Advanced Disease: Ascites, edema, dilated abdominal veins, hepatic fetor, asterixis, mental confusion/stupor/coma, enlarged umbilicus, caput medusae
- Male Cirrhosis: Hyperestrogenemia, gynecomastia, testicular atrophy, loss of male-pattern hair, yellow tinge to skin, mucous membranes below tongue in light skinned individuals
Factors Contributing to Edema
- Hypoalbuminemia
- Venous insufficiency
- Heart failure
- Medications
Fulminant Hepatitis
- Hepatic encephalopathy during acute hepatitis
Hepatic Failure
- Signs and symptoms of hepatic encephalopathy in severe acute or chronic liver disease.
Hepatic Encephalopathy
- Changes in sleep patterns
- Disorientation
- Stupor, Coma
- Asterixis (flapping tremors of body and tongue)
- Fetor hepaticus (slightly sweet/ammoniacal odor) developing in liver failure
Factors Precipitating Encephalopathy
- Gastrointestinal bleeding
- Over-diuresis
- Uremia
- Dehydration
- Electrolyte imbalances
- Infections
- Constipation
- Narcotic analgesics
Hepatopulmonary Syndrome
- Characterized by:
- Platypnea (shortness of breath)
- Orthodeoxia (oxygen desaturation) worsening in upright positions
- Related to long-standing cirrhosis and portal hypertension
Skin Disorders
- Slate-gray pigmentation with hemochromatosis (high iron levels)
- Mucocutaneous vasculitis with palpable purpura (with cryoglobulinemia in chronic hepatitis C or B)
- Kayser-Fleischer rings (golden-brown copper pigment deposits in Descemet's membrane; Wilson disease)
Liver Biopsy
- Gold standard in evaluating liver diseases, particularly chronic liver disease
Laboratory Diagnosis
- γ-glutamyl transpeptidase (GGT): To determine if elevated alkaline phosphatase (AlkP) is due to liver disease.
- Antimitochondrial antibody: Helps diagnose primary biliary cholangitis.
Diagnostic Imaging
- Ultrasound and CT: Detection of biliary duct dilation (obstructive jaundice)
- MRCP: Visualizes the biliary tree (choledocholithiasis, bile duct obstruction, congenital abnormalities)
- ERCP: Visualizes the biliary tree, allows for biopsy, and provides therapeutic options (sphincterotomy, stone extraction, nasobiliary catheter/biliary stent placement).
- MRCP is often preferred over ERCP due to no contrast media or ionizing radiation needed, images acquired faster, and the procedure being less operator dependent.
Child-Pugh Score
- Predicts the risk of major complications in cirrhosis such as bleeding from varices and spontaneous bacterial peritonitis.
MELD Score
- Measures hepatic decompensation for liver transplantation.
- Components include INR, total serum bilirubin, and creatinine.
Model for End-Stage Liver Disease (MELD) System
- Noninvasive variables such as prothrombin time (INR), serum bilirubin, and serum creatinine.
Serum Bilirubin
- Breakdown product of heme proteins
- Found in blood as conjugated and unconjugated fractions.
- Unconjugated (indirect): Insoluble in water, binds to albumin
- Conjugated (direct): Water-soluble, excreted by kidneys (bilirubinuria indicates liver disease)
- Elevated levels indicate liver damage.
Increased Unconjugated Bilirubin
- Hemolytic disorders
- Genetic conditions (Crigler-Najjar & Gilbert's)
Conjugated Hyperbilirubinemia
- Usually indicates liver or biliary tract disease.
Aminotransferases
- ALT: Found primarily in the liver, more specific for liver injury.
- AST: Found in liver, cardiac muscle, skeletal muscle, etc.; less specific than ALT for liver injury.
- Levels of 10-40 IU/L are considered normal.
γ-Glutamyl Transpeptidase (GGT)
- Located in the endoplasmic reticulum and bile duct epithelial cells.
- Elevated serum levels are less specific for cholestasis.
Alkaline Phosphatase
- Consists of isoenzymes found in liver, bone, placenta, and small intestine.
- Increased levels can be due to various factors like age, diet, pregnancy, bone growth, and liver/biliary tract or other diseases.
Hypoalbuminemia
- Decreased albumin synthesis in chronic liver disorders.
- Indicates severe liver injury.
Serum Globulins
- Group of proteins, including γ-globulins (immunoglobulins)
- Increased γ-globulins in chronic hepatitis and cirrhosis.
- Diffuse polyclonal increases in IgG – autoimmune hepatitis
- Increases in IgM – primary biliary cirrhosis
- Increases in IgA –alcoholic liver disease
Coagulation Factors
- Clotting factors are made exclusively in hepatocytes.
- Prothrombin time (PT) measures factors II, V, VII, and X; a prolonged PT indicates decreased hepatic synthetic function.
- Vitamin K is essential for the synthesis of factors II, VII, IX, and X.
- Increased PT can result from vitamin K deficiency (obstructive jaundice, fat malabsorption).
- The international normalized ratio (INR) expresses the degree of anticoagulation with warfarin therapy.
Ammonia Detoxification
- Ammonia converted to urea and excreted by the kidneys.
- Ammonia also combines with glutamic acid to form glutamine within striated muscles.
- Poor correlation between serum ammonia and hepatic function
Transient Elastography (TE)
- FibroScan - Uses ultrasound to measure liver stiffness.
- Non-invasive.
- Useful in identifying advanced fibrosis. Types that are used include chronic hepatitis C, primary biliary cirrhosis, hemochromatosis, nonalcoholic fatty liver disease, recurrent chronic hepatitis after liver transplantation.
Ultrasonography
- Identifying gallstones, dilated intrahepatic/extrahepatic biliary trees, space-occupying lesions, cysts, masses, and percutaneous biopsies. Useful in cholestasis.
Ultrasound with Doppler Imaging
- Detects patency of portal vein, hepatic artery, and hepatic veins.
- Determines blood flow direction in blood vessels.
- First test in Budd-Chiari syndrome.
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