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Evaluation of Liver Injury PowerPoint Presentation

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Description : Check out this medical presentation on Alanine Aminotransferase (alanine transaminase), which is titled "Evaluation of Liver Injury", to know about the evaluation of liver injury and liver function tests including Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Lactate dehydrogenase (LDH), Alkaline phosphatase, Bilirubin, and Albumin.

Tags : Alanine Aminotransferase, alanine transaminase, Evaluation, Liver Injury, liver function tests, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Lactate dehydrogenase (LDH), Alkaline phosphatase, Bilirubin, Albumin

Published on : Jul 05, 2021 | Views : 1908 | Downloads : 12

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Slide 1-

Evaluation of Liver Injury Mark J. Czaja Liver Research Center Albert Einstein College of Medicine Bronx, N.Y.
Slide 2-

Liver Function Tests Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Lactate dehydrogenase (LDH) Alkaline phosphatase Bilirubin Albumin
Slide 3-

Mechanisms of Liver Dysfunction Direct cellular injury Blockage in bile flow Impaired blood flow
Slide 4-

Direct Cellular Injury - HCV Infection
Slide 5-

Blockage in Bile Flow - Biliary Atresia
Slide 6-

Impaired Blood Flow - CHF
Slide 7-

Consequences of Liver Injury liver cell injury liver cell death proliferation matrix deposition sufficient inadequate altered architecture recovery liver failure cirrhosis
Slide 8-

Types of Liver Tests True tests of liver function Biochemical markers of liver injury Biochemical markers of specific liver diseases
Slide 9-

Testable Biochemical Liver Function Ability to transport organic anions Capacity to metabolize certain substances Capability to synthesize various proteins
Slide 10-

Steps in Organic Anion Transport Delivery and uptake Metabolic alteration Secretion and excretion
Slide 11-

Bilirubin Tetrapyrole Toxic in neonates - kernicterus Derived from: Senescent RBC (70-80%) Hemoproteins (20-30%) Ineffective erythropoiesis
Slide 12-

Bilirubin Formation heme biliverdin bilirubin heme oxygenase biliverdin reductase Transport: hydrophobic due to internal H-bonding circulates bound to albumin
Slide 13-

Bilirubin Metabolism UCB ligandin glucuronyl transferase BMG BDG Alb UCB BMG BDG Plasma Hepatocyte Bile BMG BDG
Slide 14-

Bilirubin Elimination Intestine BMG (20%) + BDG (80%) +UCB (trace) Deconjugated to urobilinogen Excreted or reab-sorbed (20%) Urine BMG and BDG No UCB
Slide 15-

Measurement of Serum Bilirubin Normal concentration < 1 mg/dl Conjugated < 5% Jaundice if > 3 mg/dl Detected by diazo reaction - cleaved to colored azo-dipyrole Conjugated reacts rapidly (direct) Unconjugated reacts slowly (indirect)
Slide 16-

Differential Diagnosis I Prehepatic Intrahepatic Congenital Acquired Posthepatic
Slide 17-

Differential Diagnosis II Unconjugated hyperbilirubinemia Increased bilirubin production (hematological) Decreased uptake (drug) Decreased conjugation (congenital) Conjugated hyperbilirubinemia Congenital Drug Liver disease Biliary obstruction
Slide 18-

Inherited Disorders Causing Unconjugated Hyperbilirubinemia Crigler-Najjar syndrome Type 1 – absent GT Type 2 – reduced GT activity Gilbert’s syndrome – reduced GT activity due to genetic defect in TATAA element of GT promoter
Slide 19-

Inherited Disorders Causing Conjugated Hyperbilirubinemia Dubin-Johnson syndrome – mutations in multidrug resistance associated protein 2 (MRP2) Rotor’s syndrome – genetic defect
Slide 20-

Hepatic Metabolic Capacity Clearance must depend on total functional mass or metabolic activity Hepatic drug metabolism - [14C]amino-pyrine breath test Galactose elimination Not used clinically
Slide 21-

Hepatic Synthetic Capacity Most major plasma proteins are made in the liver Decreased hepatocytes = decreased protein synthesis and release Albumin and coagulation factors are clinically important
Slide 22-

Albumin 50% of all synthesized hepatic protein Determinant of plasma oncotic pressure Important transport protein
Slide 23-

Serum Albumin Levels Long half-life of 20 days Large hepatic synthetic reserve Decreased with persistent, large injury Decreased in chronic liver disease Poor prognostic sign
Slide 24-

Non-hepatic Causes of Hypoalbuminemia Severe malnutrition Renal or GI loss Glomerulopathy, HIV enteropathy High catabolism Infections, burns
Slide 25-

Coagulation Factors Half-lives of hours to days Liver synthesizes I, II, V, VII, IX, and X Large synthetic reserve
Slide 26-

Prothrombin Time (PT) PT detects abnormalities in I, II, V, VII and X (extrinsic pathway) PT is increased in liver disease Best prognostic indicator Acute liver disease Chronic liver disease
Slide 27-

Non-hepatic Causes of Elevated PT Congenital coagulation factor deficiencies Consumptive coagulopathies Vitamin K deficiency (II, VII, IX, X)
Slide 28-

To Rule Out Vitamin K Deficiency Any patient with an elevated PT Parental vitamin K for 3 days Normalization of PT - vitamin K deficiency Failure to normalize - hepatocellular disease
Slide 29-

Serum Immunoglobulins Not produced by hepatocytes Frequently elevated in liver disease Secondary to inflammatory process ? produced by antigen shunting
Slide 30-

Biochemical Markers of Liver Injury
Slide 31-

Liver Enzymes Low levels always present in serum Leak out from cell after injury Very sensitive Magnitude of abnormality does not correlate well with degree of injury
Slide 32-

Aspartate Aminotransferase (AST) Serum glutamic-oxaloacetic transaminase (SGOT) Transfers an a-amino group of aspartate to a-keto group of ketoglutaric acid Present in skeletal muscle, kidney, brain
Slide 33-

Alanine Aminotransferase (ALT) Serum glutamic-pyruvic transaminase (SGPT) Transfers an a-amino group of alanine to a-keto group of ketoglutaric acid Present principally in liver
Slide 34-

AST and ALT Elevated in most liver diseases Highest levels are in acute liver diseases Only slight elevations in chronic liver diseases Usually increase in parallel
Slide 35-

AST/ALT in Alcoholic Hepatitis Transaminases rarely exceed 300 AST:ALT >2
Slide 36-

Factors Affecting AST/ALT Depressed by pyridoxine (vit. B6) deficiency Decreased by uremia and renal dialysis
Slide 37-

AST/ALT Controversies Should lower normal limits be used in females? Females < 30 vs. males < 40 Are the normal limits too high? Females < 20 and males < 30
Slide 38-

Lactate Dehydrogenase (LDH) Component of classic LFT’s Highly non-specific
Slide 39-

Tests of Impaired Hepatic Excretion Increased In Cholestasis Intra-hepatic biliary tract obstruction Extra-hepatic biliary obstruction
Slide 40-

Alkaline Phosphatase Hydrolyzes phosphate esters at alkaline pH Also present in bone, kidney, placenta, intestine Mainly liver and bone in adults Increased in children from bone growth Placental form during pregnancy
Slide 41-

Elevated Alkaline Phosphatase Can occur in any liver disease Highest with cholestasis or biliary tract obstruction Elevated in infiltrative diseases Due to increase synthesis and secretion
Slide 42-

Alkaline Phosphatase Isoenzymes
Slide 43-

5'-Nucleotidase Hydrolyzes 5'- adenosine monophosphate Mainly present in liver Increases along with alkaline phosphatase
Slide 44-

g-Glutamyl Transpeptidase (GGTP) Transfers g-glutamyl groups Widely distributed Sensitive correlate to alkaline phosphatase Non-specific (alcoholism, MI, DM, pancreatic disease, renal failure)
Slide 45-

Biochemical Markers of Specific Liver Diseases
Slide 46-

Etiology-specific Liver Tests Viral hepatitis serologies Serum ferritin level Ceruloplasmin level Alpha1-antitrypsin level Antimitochondrial antibody titer
Slide 47-

Viral Hepatitis Serology HAV – anti-HAV IgM and IgG HBV – HBsAg, anti-HBsAg, and anti-HBcAg HCV – anti-HCV, HCV RNA
Slide 48-

Serum Ferritin Widely distributed storage protein Levels reflect body iron stores Elevated in primary hemochromatosis Elevated in acute inflammation and cirrhosis
Slide 49-

Serum Ceruloplasmin Copper-binding protein Decreased in 95% of patients with Wilson’s disease 20% of heterozygotes have decreased levels
Slide 50-

a1-Antitrypsin Inhibits serum trypsin Major component of a1-globulin Deficiency cause of neonatal hepatitis
Slide 51-

Antimitochondrial Antibody (AMA) Directed against mitochondrial enzyme pyruvate dehydrogenase complex Positive in 90% of patients with primary biliary cirrhosis
Slide 52-

Interpretation of Abnormal LFT’s Examine multiple tests Consider non-hepatic causes Determine the most abnormal tests
Slide 53-

Hepatocellular vs. Cholestatic
Slide 54-

Case 1 ALT 2045 (15-45) AST 2300 (15-45) Alk Phos 273 (50-150) Bili 3.9 (0.1-1.0) Alb 4.2 (3.5-5.5) PT 11.5 (10-12) 25 yo IVDA c/o 1 week of nausea, vomiting, and myalgias. Physical exam revealed jaundice.
Slide 55-

Hepatocellular W/U H & P EtOH, medications, transfusions Risk for viral hepatitis Risk factors for NASH Autoimmune features Etiology-specific LFT’s USG and liver biopsy
Slide 56-

HBV Infection - HBcAg Staining
Slide 57-

Case 2 ALT 75 (15-45) AST 115 (15-45) Alk Phos 650 (50-150) Bili 10.2 (0.1-1.0) Alb 4.2 (3.5-5.5) PT 11.0 (10-12) 67 yo c/o several months of weight loss, and 1 week of nausea, vomiting, and myalgias. Physical exam revealed cachexia and jaundice.
Slide 58-

Cholestatic W/U H & P medications, gallstones, weight loss AMA USG ERCP liver biopsy dilated ducts normal
Slide 59-

Pancreatic Carcinoma - ERCP