Liver Function Notes PDF

1 Approach to Liver Diseases Liver Function Evaluation 2 LIVER ▪Largest organ/ gland in the body ▪Weighs 1–1.5 kg Blood Supply ▪Hepatic Artery - 20% of the blood flow ▪Portal Vein- 80% is nutrient-rich blood 3 Portal triad...

1 Approach to Liver Diseases Liver Function Evaluation 2 LIVER ▪Largest organ/ gland in the body ▪Weighs 1–1.5 kg Blood Supply ▪Hepatic Artery - 20% of the blood flow ▪Portal Vein- 80% is nutrient-rich blood 3 Portal triad Branches of hepatic artery Portal vein, Tributary of bile duct 4 LIVER Cells 1. Hepatocytes- 2/3 of the organ’s mass. 2. Kupffer cells - members of RES 3. Stellate - Ito or fat-storing cells 5 LIVER Acinus - physiologic unit of the liver 3 Zones Zone 1- Hepatic arterial and portal venous blood entering acinus from portal areas Zone 2- Hepatocytes Zone 3- Sinusoids to terminal hepatic veins 6  LIVER Kupffer cells ▪lie within sinusoidal vascular space ▪represent largest group of fixed macrophages in the body. Stellate cells – fat storing cells ▪ located in the space of Disse ▪not prominent unless activated, when they produce collagen and matrix. 7 Hepatocytes Functions ▪Synthesis of proteins (albumin, coagulation factors) ▪Production of bile 8 Hepatocytes Functions ▪Regulation of nutrients (glucose, glycogen, lipids, cholesterol, amino acids) ▪Metabolism and conjugation of lipophilic compounds (bilirubin, anions, cations, drugs) 9 Liver Function Tests Measure of hepatic conjugation and excretion Bilirubin Measures of protein synthesis Serum albumin level Prothrombin time 10  LIVER DISEASES Category 1. Hepatocellular- inflammation and necrosis Viral hepatitis , Alcoholic liver disease 2. Cholestatic (obstructive)- inhibition of bile flow Gallstone, Malignant obstruction Primary biliary cholangitis Drug-induced liver diseases 3. Mixed- both hepatocellular and cholestatic injury 11 CLINICAL HISTORY S/S Fatigue, Weakness Nausea Poor appetite Malaise Jaundice, dark urine Light stools, Pruritus abdominal pain 12  Signs and Symptoms Fatigue - most common most characteristic symptom of liver disease Diarrhea - uncommon in liver disease except with severe jaundice 13 S/S Pain from stretching or irritation of Glisson’s capsule which surrounds the liver and is rich in nerve endings. 14 Severe pain Gallbladder disease Liver abscess Veno-occlusive disease 15 S/S Itching Acute and chronic liver disease Cholestatic forms Primary biliary cholangitis and sclerosing cholangitis (Biliary obstruction, Drug-induced cholestasis) 16 Jaundice ▪Hallmark symptom of liver disease ▪Most reliable marker of severity 17 Liver disease Familial Causes Wilson disease Hemochromatosis α1 antitrypsin deficiency Intrahepatic cholestasis 18 PHYSICAL EXAMINATION ▪Icterus ▪Hepatic tenderness ▪Splenomegaly ▪Spider angiomata ▪Palmar erythema 19 Advanced Liver disease ▪Ascites, Edema ▪Dilated abdominal veins ▪Hepatic fetor, Asterixis ▪Mental confusion, Stupor, Coma 20 Advanced Liver Disease Umbilical Hernia from ascites Caput medusa collateral veins radiating from the umbilicus results from recanulation of the umbilical vein. 21  PHYSICAL EXAMINATION In male patients with cirrhosis Hyperestrogenemia Gynecomastia Testicular atrophy , Loss of male-pattern hair Icterus - Sclera Yellow tinge to the skin Dark-skinned - mucous membranes below tongue 22 Factors contributes to edema ▪Hypoalbuminemia ▪Venous insufficiency ▪Heart failure ▪Medications. 23 Fulminant hepatitis Hepatic encephalopathy during acute hepatitis 24 Hepatic failure S/S of hepatic encephalopathy in severe acute or chronic liver disease 25 Hepatic encephalopathy Change in sleep patterns Disorientation Stupor , Coma 26 Hepatic encephalopathy Asterixis Flapping tremors – body, tongue Fetor hepaticus slightly sweet, ammoniacal odor develops in liver failure 27 Factors precipitating encephalopathy Gastrointestinal bleeding Over-diuresis Uremia Dehydration Electrolyte imbalance Infection, constipation Use of narcotic analgesics 28 Hepatopulmonary Syndrome In long-standing cirrhosis & portal hypertension Triad Liver disease Hypoxemia Pulmonary arteriovenous shunting 29 Hepatopulmonary syndrome ▪characterized by 1. Platypnea 2. Orthodeoxia- shortness of breath oxygen desaturation occur paradoxically upon assumption of an upright position. 30 Skin disorders Slate-gray pigmentation of the skin ▪seen with hemochromatosis ▪if iron levels are high for a prolonged period. Mucocutaneous vasculitis with palpable purpura ▪Cryoglobulinemia of chronic hepatitis C ▪Chronic hepatitis B 31 Skin changes Kayser-Fleischer rings ▪Wilson disease ▪consist of a golden-brown copper pigment deposited in Descemet’s membrane at periphery of the cornea ▪best seen by slit-lamp examination 32 Liver Biopsy ▪gold standard in evaluation of patients with liver disease, particularly chronic liver disease. 33 Laboratory Diagnosis γ-glutamyl transpeptidase (γGT) -To define whether AlkP elevations due to liver disease Antimitochondrial antibody- Primary biliary cholangitis 34 Diagnostic Imaging Ultrasound and CT -Sensitive for detecting biliary duct dilation - Obstructive jaundice. 35 Diagnostic Imaging For visualization of the biliary tree 1. Magnetic resonance cholangiopancreatography (MRCP) Choledocholithiasis Useful in Dx : Bile duct obstruction Congenital biliary abnormalities 2. Endoscopic retrograde cholangiopancreatography (ERCP) 36 Diagnostic Imaging MRCP advantages over ERCP No need for contrast media or ionizing radiation images can be acquired faster Procedure is less operator dependent No risk of pancreatitis. 37 ERCP ▪More valuable in ampullary lesions and primary sclerosing cholangitis ▪Permits biopsy ▪Direct visualization of the ampulla and common bile duct 38 ERCP ▪Provides several therapeutic options in obstructive jaundice Sphincterotomy Stone extraction Placement of nasobiliary catheters and biliary stents. 39 Child-Pugh score Predicts the likelihood of major complications of cirrhosis Bleeding from varices spontaneous bacterial peritonitis. 40 MELD score ▪measure of hepatic decompensation ▪to allocate organs for liver transplantation Components INR Total serum bilirubin Creatinine 41 Model for End-Stage Liver Disease (MELD) system Noninvasive variables Prothrombin time expressed as (INR) Serum bilirubin level Serum creatinine concentration. 42 MELD score Model for End-Stage Liver Disease, Tool used to estimate survival of patients with end- stage liver disease Assess operative risk of patients with cirrhosis. 43 Serum Bilirubin Bilirubin breakdown product of the porphyrin ring of heme-containing proteins found in the blood in 2 fractions—conjugated and unconjugated. Unconjugated fraction - indirect fraction insoluble in water bound to albumin in the blood. Conjugated (direct) bilirubin fraction water-soluble can be excreted by the kidney. 44 Total serum bilirubin 1- 1.5 mg/dL If direct-acting fraction is 15% of total- indirect. Conjugated bilirubin 0.3 mg/dL. Higher serum bilirubin, greater hepatocellular damage. 45 Increased Unconjugated bilirubin Hemolytic disorders Genetic conditions Crigler-Najjar and Gilbert’s syndromes 46 Conjugated hyperbilirubinemia Almost always implies liver or biliary tract disease. Rate-limiting step in bilirubin metabolism not conjugation of bilirubin transport of conjugated bilirubin into the bile canaliculi. 47 Unconjugated bilirubin bound to albumin in the serum not filtered by the kidney. Conjugated bilirubin bilirubin in urine Bilirubinuria→ presence of liver disease. 48 Aminotransferases ALT is found primarily in the liver and is therefore a more specific indicator of liver injury. AST found in liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes, erythrocytes 49 Aminotransferases (transaminases) - sensitive indicators of liver cell injury , hepatitis. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Aminotransferases 10 to 40 IU/L. 50 γ-glutamyl transpeptidase (GGT) ▪located in the endoplasmic reticulum and in bile duct epithelial cells. ▪elevation in serum is less specific for cholestasis 51 Alkaline phosphatase Consists of Isoenzymes ▪Liver ▪Bone ▪Placenta ▪Small intestine 52 Increased Alkaline phosphatase ▪Patients > 60 yo 1–1.5x ▪Blood types O and B after eating a fatty meal ▪Children and adolescents undergoing rapid bone growth ▪Late in normal pregnancies due to influx of placental ALP ▪ Liver-derived alkaline phosphatase - not totally specific for cholestasis, < 3x elevation- seen in type of liver disease. 53 Increased Alkaline phosphatase > 4x Cholestatic liver disorders Infiltrative liver diseases Cancer Amyloidosis Bone conditions rapid bone turnover (Paget’s disease). 54 Hypoalbuminemia Decreased albumin synthesis. Chronic liver disorders Reflects severe liver damage 55 Serum Globulins ▪Group of proteins made up of γ globulins (immunoglobulins) ▪γ globulins - increased in chronic liver disease- chronic hepatitis and cirrhosis. 56 Serum Globulins Diffuse polyclonal increases in IgG levels - autoimmune hepatitis Increases in the IgM levels - primary biliary cirrhosis Increases in the IgA levels - alcoholic liver disease. 57 COAGULATION FACTORS Clotting factors made exclusively in hepatocytes. single best acute measure of hepatic synthetic function Prothrombin time- measures factors II, V, VII, and X. 58 COAGULATION FACTORS Biosynthesis of factors II, VII, IX, X depends on vitamin K. Increased Prothrombin time- vitamin K deficiency such as obstructive jaundice fat malabsorption of any kind. International normalized ratio (INR) -used to express the degree of anticoagulation on warfarin therapy. 59 Ammonia detoxification Ammonia by converted to urea, excreted by kidneys. Striated muscle combined with glutamic acid to form glutamine. Poor correlation of serum ammonia and hepatic function. 60 Transient elastography (TE) ▪marketed as FibroScan ▪uses ultrasound waves to measure hepatic stiffness noninvasively ▪accurate for identifying advanced fibrosis 61 Transient elastography (TE) ▪FibroScan Chronic hepatitis C Primary biliary cirrhosis Hemochromatosis Nonalcoholic fatty liver disease Recurrent chronic hepatitis after liver transplantation 62 Ultrasonography In Cholestasis Identifies ▪ Gallstones, Dilated intrahepatic or extrahepatic biliary tree ▪ Space-occupying lesions within the liver ▪ Cystic and solid masses ▪ Direct percutaneous biopsies. 63 Ultrasound with Doppler imaging ▪detects patency of portal vein, hepatic artery, hepatic veins ▪determines the direction of blood flow. ▪first test ordered in Budd Chiari syndrome. 64 Referrences Harrison’s Principles of Internal Medicine 20th Ed 65 66