Liver Disease atf.pdf

AfraTafreeh.com Liver Disease Jason Ryan, MD, MPH Liver Tests Aspartate Aminotransferase (AST) Located in mitochondria Alcohol is mitochondrial toxin ↑ AST> ↑ALT in alcoholic hepatitis Alanine Aminotransferase (ALT) AfraTafreeh.com Lo...

AfraTafreeh.com Liver Disease Jason Ryan, MD, MPH Liver Tests Aspartate Aminotransferase (AST) Located in mitochondria Alcohol is mitochondrial toxin ↑ AST> ↑ALT in alcoholic hepatitis Alanine Aminotransferase (ALT) AfraTafreeh.com Located in cytoplasm ↑ ALT > ↑AST in most types of hepatitis with cellular damage  AfraTafreeh.com Liver Tests Alkaline phosphatase (Alk Phos) Enzyme from liver, bones, GI tract Precise function not known ↑ synthesis with obstructed bile flow (cholestasis) Serum levels rise with cholestasis Levels rise in many non-liver conditions Pregnancy (placenta) Thyroid disease Bone disease Liver Tests Gamma-glutamyl transpeptidase (GGT) Similar to alk phos but not elevated in bone disease Used to determine origin of alk phos elevation ↑ Alk Phos plus ↑ GGT = hepatobiliary cause of ↑ Alk Phos Also elevated after heavy alcohol consumption AfraTafreeh.com 5'-Nucleotidase Bilirubin (total, direct, indirect)  AfraTafreeh.com Liver Tests Tests of Synthetic Function Albumin PT/PTT (coagulation factors) Glucose Need liver for glycogen breakdown and gluconeogenesis Abnormalities = severe liver disease Alcoholic Liver Disease Three ways alcohol (ethanol) can damage liver #1: Alcoholic fatty liver disease #2: Acute hepatitis #3: Cirrhosis AfraTafreeh.com Wikipedia/Public Domain  AfraTafreeh.com Alcoholic Fatty Liver Disease Accumulation of fatty acids (fatty infiltration of liver) Usually asymptomatic among heavy drinkers May cause hepatomegaly on exam Abnormal LFTs (AST>ALT) Often reversible with cessation of alcohol ↑ risk of cirrhosis ToNToNi/Wikipedia Liver Lobules AfraTafreeh.com 1 2 3 Reytan /Wikipedia  AfraTafreeh.com Portal Triad Reytan /Wikipedia  Fatty infiltration in Liver Zones Alcoholic Liver Disease begins here Hepatic Artery (also fibrosis in cirrhosis) Hepatic Vein Portal Vein Bile Duct Zone I Zone II Zone III AfraTafreeh.com Periportal Mid Zone Centrilobular  AfraTafreeh.com NAFLD Non-alcoholic Fatty Liver Disease Fatty infiltration of liver not due to alcohol NAFL: Fatty liver NASH: Steatohepatitis (fat and inflammation) Often asymptomatic Abnormal LFTs (ALT>AST) May progress to cirrhosis Associated with obesity May improve with weight loss Alcoholic Hepatitis Classically occurs after heavy, binge drinking on top of long history of alcohol consumption Toxic effects from acetaldehyde Symptoms Fever AfraTafreeh.com Jaundice RUQ pain/tenderness Alexandre Normand/Flikr  AfraTafreeh.com Mallory bodies Classic histopathology finding alcoholic liver disease Cytoplasmic inclusions Damaged intermediate filaments in hepatocytes Wikipedia Budd Chiari Syndrome Thrombosis of hepatic vein Abdominal pain, ascites, hepatomegaly Zone 3 congestion, necrosis, hemorrhage Common causes: AfraTafreeh.com Myeloproliferative disorder (P. vera, ET, CML) Hepatocellular carcinoma OCP/Pregnancy Hypercoagulable states  AfraTafreeh.com Right Heart Failure “Cardiac cirrhosis” Rare cause of liver failure Chronic liver edema → cirrhosis Results in nutmeg liver Mottled liver like a nutmeg Also seen Budd Chiari David Monniaux/Wikipedia Reye’s Syndrome Rare cause of liver failure and encephalopathy Children with viral infections who take aspirin Classically chicken pox (varicella zoster) and influenza B Rapid, severe liver failure Evidence that aspirin inhibits beta oxidation AfraTafreeh.com Mitochondrial damage seen Fatty changes in liver (hepatomegaly) Vomiting, coma, death Avoid aspirin in children (except Kawasaki’s)  AfraTafreeh.com α1 Anti-trypsin Deficiency Inherited (autosomal co-dominant) Decreased or dysfunctional AAT AAT balances naturally occurring proteases Proteases Anti-Proteases α1 Anti-trypsin Deficiency Lung Emphysema Imbalance between neutrophil elastase (destroys elastin) and elastase inhibitor AAT (protects elastin) Liver AfraTafreeh.com Cirrhosis Abnormal α1 builds up in liver (endoplasmic reticulum) Pathologic polymerization of AAT Occurs in endoplasmic reticulum of hepatocytes  AfraTafreeh.com α1 Anti-trypsin Deficiency AAT polymers stain with PAS resist digestion by diastase (unlike glycogen) Jerad M Gardner, MD Liver Abscess Walled-off infection of the liver In the US usually bacteria Bacteremia Cholangitis (GN Rods; Klebsiella often identified) Entamoeba histolytica (protozoa) AfraTafreeh.com Cysts in contaminated water → bloody diarrhea (dysentery) Ascends in the biliary tree Echinococcus (helminth) Fecal-oral ingestion of eggs Massive liver cysts Hellerhoff/Wikipedia  AfraTafreeh.com Viral Hepatitis Hepatitis A, B, C, D, or E Very high AST/ALT Often >1000 (>25x normal) Hyperbilirubinemia and jaundice If severe, may see abnormal synthetic function Hypoglycemia, elevated PT/PTT, low albumin Diagnosed via viral antibody tests Autoimmune Hepatitis Autoimmune inflammation of the liver Most common among women in 40s/50s Range of symptoms Asymptomatic → acute liver disease → cirrhosis Anti-nuclear antibodies (ANAs) AfraTafreeh.com Most common antibody abnormality Sensitive, not specific Anti-smooth muscle antibodies (ASMA) More specific for AHA Treatment: steroids and immunosuppressants  AfraTafreeh.com Tylenol Overdose Acetaminophen, Paracetamol, APAP (N-acetyl-para-aminophenol) Maximum recommended dose = 4 grams per 24 hours Overdose causes acute liver failure (hepatic necrosis) Extremely high AST/ALT (in 1000s) Katy Warner/Wikipedia Tylenol Overdose Treatment Activated charcoal may prevent absorption N-acetylcysteine is treatment of choice Used to replenish glutathione Usually given orally to patients with overdose AfraTafreeh.com N-acetylcysteine Cysteine Glutathione  AfraTafreeh.com Tylenol Overdose Treatment Three metabolites of acetaminophen NAPQI is toxic to liver N-acetyl-p-benzoquinone imine Metabolized by glutathione Wikipedia/Public Domain Shock Liver Ischemic Hepatitis Diffuse liver injury from hypoperfusion Often seen in ICU patients with shock from any cause Markedly elevated AST/ALT (1000s) Usually self-limited AfraTafreeh.com Pathology: zone 3 necrosis (near central vein)