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Etiologies of Chronic Liver Disease

Mechanisms of Chronic Liver Injury. Hepatocyte InjuryInflammation primaryInjury primary

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Etiologies of Chronic Liver Disease

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    1. Etiologies of Chronic Liver Disease Infections, esp. viral Toxins Genetic Drugs Autoimmune Vascular Biliary

    2. Mechanisms of Chronic Liver Injury Hepatocyte Injury Inflammation primary Injury primary – followed by inflammation Biliary Obstruction Hepatic venous obstruction

    8. Etiologies of Chronic Hepatitis Hepatitis C Hepatitis B (w/wo Delta) Autoimmune Hepatitis Drugs Wilson’s Disease

    9. Pathogenesis of Liver Injury with Chronic Biliary Obstruction Obstruction of bile flow Bile acid, copper accumulation Alterations in cannicular membrane and tight junctions Condensation of pericannicular microfilaments Fibrosis (necrosis and inflammation)

    12. Cirrhosis

    16. Why Do Varices Bleed?

    17. Options for Control of Variceal Bleeding Medical Vasopressin (or glypressin) + NTG Somatostatin (or octreotide) Beta blockers Procedures SB, Minnesota, or Linton tube Endoscopic sclerotherapy or band ligation TIPS Surgical Shunts Variceal interruption Transplant

    19. Elements of Ascites Formation in Cirrhosis Portal hypertension Decreased renal excretion of Na and water Decreased serum oncotic pressure Lead to an increased formation of hepatic lymph exceeding the capacity of the thoracic duct

    20. Classical Underfilling Theory Overflow Theory Sinusoidal Portal Hypertension

    22. Hepatorenal Syndrome (Functional Renal Failure) Kidney pathologically normal Reduced blood flow to renal cortex Reduced GFR Hypertonic urine, reduced urine Na Distinguish from other causes of renal failure

    23. Complicated Ascites in Cirrhosis Spontaneous bacterial peritonitis Tuberculous peritonitis Pancreatic ascites Cancer (esp. hepatoma) Budd-Chiari syndrome

    26. First Known Description of Hepatic Encephalopathy “I’m a great eater of beef but believe it does harm to my wit”

    27. Stages of Hepatic Encephalopathy Stage 0 - Subclinical; psychomotor test abnormalities Stage 1 - Lethargy and confusion or excitation, sleep disturbance, decreased attention Stage 2 - Somnolence, inappropriate behavior Stage 3 - Stupor but arousable, speech incomprehensible Stage 4 - Coma

    31. Hypotheses Concerning the Mechanism of Hepatic Encephalopathy Ammonia Synergistic toxins – ammonia, mercaptans, and free fatty acids Increased activity of GABA – benzodiazepine neurotransmission False neurotransmitters – aromatic amines

    34. Precipitants of Hepatic Encephalopathy Excess nitrogen load Drugs (sedatives, analgesics, diuretics) Renal failure Electrolyte/acid-base abnormalities Infection Surgical procedures Constipation

    35. Management of Hepatic Encephalopathy Search for and correction of precipitating factors Reduce dietary protein (40 g or less) Laxatives, enemas Lactulose, antibiotic (neomycin), or combination Criteria of response

    36. Lactulose: Mechanism of Altering Colonic Nitrogen Metabolism Stimulate bacterial growth and nitrogen incorporation Inhibit bacterial catabolism of amino acids, peptides, … Cathartic effect (Ammonia trapping)

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