Untitled Quiz

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.