Module 7 Pathophysiology PDF

Summary

This document provides detailed information about liver inflammation, viral hepatitis (A, B, C, D, E), and associated factors. It covers etiology, clinical features, and diagnostic aspects. This is a study guide.

Full Transcript

MODULE 7: PATHOPHYSIOLOGY I. HEPATOBILLIARY TREE DISORDERS [A. Hepatitis] -- liver inflammation Etiology: \- viral infection \- toxins \- drugs \- other immune mediated **I. Viral Hepatitis** Acute Viral Hepatitis Definition -- viral hepatitis lasting [\< 6 months] Clinical Features: \-...

MODULE 7: PATHOPHYSIOLOGY I. HEPATOBILLIARY TREE DISORDERS [A. Hepatitis] -- liver inflammation Etiology: \- viral infection \- toxins \- drugs \- other immune mediated **I. Viral Hepatitis** Acute Viral Hepatitis Definition -- viral hepatitis lasting [\< 6 months] Clinical Features: \- most are subclinical \- early symptoms or prodrome ([flu-like illness]) may precede jaundice by 1-2 weeks \- nausea, vomiting, anorexia, taste/smell disturbance (aversion to cigarettes) headaches, fatigue, malaise, myalgias \- low-grade fever may be present arthralgia and urticaria (especially hepatitis B) \- clinical jaundice (icteric) phase (50% of cases) lasting days to week - Pale stools and dark urine 1-5 days prior to icteric phase - Hepatomegaly plus RUQ pain - Splenomegaly and cervical lymphadenopathy (10-20% of cases) \- Hepatic enzymes - Hepatocellular necrosis which causes increased AST, ALT \> 10-20X normal - ALP and Bilirubin minimally increased - WBC normal or slightly decreased initially [Viral Hepatitis -- (A&E=Acute, B&D= Acute & Chronic, C=Chronic)] [**A**. HEPATITIS A VIRUS (Acute) ] ETIOLOGY \- Hepatitis A Virus (Most Common Viral Hepatitis Worldwide) PATHOGENESIS \- Fecal-Oral Transmission \- 2-6wk Incubation \- Virus is Directly Cytopathic to the Liver -- But Does NOT lead to Cirrhosis Clinical Features: \- Acute Symptoms ONLY; No Chronic. \- Viremia \> Fever, Malaise, Anorexia, Nausea, Arthralgia Signs: \- Jaundice (After 1-2wks) (Due to Intrahepatic Cholestasis) - Inc Conjugated Bilirubin \- +/- Hepatomegaly \- +/- Splenomegaly \- +/- Tender Lymphadenopathy \- Rarely - Hepatic Encephalopathy & Death. Investigations: \- LFTs - (Everything Raised) \- Hep A Serology \- Hep A PCR Prognosis: \- Usually Self-Limiting with Supportive Treatment Only [B. HEPATITIS E VIRUS (ACUTE)] \- (Very Similar to Hepatitis A; But HIGH MORTALITY in PREGNANCY \[20% \> DIC in 3rd Trimester\]) Etiology: -- Hepatitis E Virus (A Herpesvirus) Pathogenesis: \- Virus is Directly Cytopathic to the Liver Clinical Features: \- Fecal-Oral Transmission (Incl. Vectors: Dogs/Pigs/Rodents) Clinical Picture: \- (Same as Hep A) Investigations: \- LFTs ʹ (Everything Raised) \- Hep E Serology \- Hep E PCR Prognosis: \- 1-2% Mortality (From Fulminant Hepatic Failure) \- 20% Mortality in Pregnancy (From DIC in 3rd Trimester) [ACUTE AND CHRONIC VIRAL HEPATITIS] [A. HEPATITIS B VIRUS (HBV)] \- transmission via parenteral route or equivalent \- vertical transmission - occurs during 3rd trimester or early post-partum - HBsAg +ve, HBeAg +ve mothers ----\> 90% of infants infected - HBsAg +ve, anti-HBe +ve mothers ---- \> 10-15% infected - give HBIG and full HBV vaccination to newborns of HBsAg +ve mothers (90% effective) \- incubation period 6 weeks to 6 months \- infectivity: during HBsAg positivity \- high-risk groups - neonates of carriers ("vertical transmission") - partners of acutely and chronically infected individuals, with male homosexuals at particular risk - IV drug users - hospital employees - patients from endemic country **[Hepatitis B serology:]** \- HBsAg: surface antigen \- HBeAg: e antigen (a component of HBV core); marker of viral replication \- HBcAg: core antigen (cannot be measured in serum) \- Both HBsAg and HBeAg are present during acute hepatitis B \- Anti-HBs follows HBsAg clearance and confers long-term immunity \- Anti-HBe and anti-HBc appear during the acute and chronic phases of the illness but do not provide immunity! \- Anti - HBe indicates low infectivity Prevention: \- HBV vaccine = recombinant HBsAg \- Seroconversion rates about 94% after 3 injections \- Hepatitis B immune globulin (HBIG) = antiHBs - for needle stick, sexual contact, and neonates born to mothers with acute or chronic infection [B.] [HEPATITIS C VIRUS (HCV)] \- Transmission is chiefly parenteral - Transfusions (HCV is the most common cause of post-transfusion hepatitis) - IV drugs use - Sexual transmission occurs but risk is less than with HBV - 40% of cases have no risk factors \- Clinical incubation period 5-10 weeks \- AST and ALT levels fluctuate (unlike Hep A or B) \- More than half progress to chronic liver disease (see below) \- Serology - HCV RNA (detected by PCR assay) o anti-HCV - develops in 6-8 weeks in 85% of patients - persists in chronic infection and does not confer immunity Prevention: \- no accepted vaccine for HCV [C. HEPATITIS D (HDV)] \- infectious only in the presence of HBV because HBV surface antigens are required for replication \- 2 patterns of transmission - nonparental transmission by close personal contact in endemic areas (Mediterranean) - transmission by blood products in non-endemic areas (IV drugs, blood transfusions) \- coinfection: simultaneous HBV and HDV infection \- superinfection: appears as clinical exacerbation in a chronic HBV patient \- predisposes to severe or fulminant course \- Serology: HBsAg, anti-HDV IgM or anti-HDV IgG Prevention: HBV vaccine D. HEPATITIS E VIRUS (HEV) \- fecal-oral transmission occurring in epidemics in Asia, Africa, Central America \- Most have mild disease, but in 3^rd^ trimester of pregnancy 10-20% have fulminant liver failure \- Serology: Anti-HEV Prevention: no vaccine available DRUG INDUCED LIVER DISEASE / DRUG INDUCED HEPATITIS SPECIFIC DRUGS: I. [Acetaminophen ] - Metabolized by hepatic cytochrome P450 system - Can cause fulminant hepatic failure (transaminases \> 1,000 U/L) - Requires 10-15g in normals, 4-6g in alcoholics/anticonvulsant users **Mechanism:** - High acetaminophen doses saturate glucuronidation and sulfation elimination pathways, therefore a reactive metabolite is formed which covalently binds to hepatocyte membrane **Presentation:** - First 24 hrs: nausea and vomiting usually within 4-12 hours - Next 24-48 hrs: hepatic necrosis resulting in increased aminotransferases, jaundice, possibly hepatic encephalopathy, acute renal failure death - After 48 hrs: continue hepatic necrosis/resolution - Note: potential delay in presentation in sustained-release products **-** Blood levels of acetaminophen correlate with the severity of hepatic injury **Therapy:** - Gastric lavage/emesis (if 2 hrs after ingestion) - Oral charcoal - N-acetylcysteine PO/IV within 8-10 hours of ingestion, most effective for up to 72 hours (promotes hepatic glutathione synthesis) [II. Chlorpromazine] - Cholestasis in 1% after 4 weeks; often with fever, rash, jaundice, pruritus and eosinophilia [III. INH] - 20% develop elevated transaminases but \< 1% develop clinically significant disease - Susceptibility to injury increases with age [IV. Methotrexate ] - May rarely cause cirrhosis, especially in the presence of obesity, diabetes, alcoholism - Scarring develops without symptoms or changes in liver enzymes, therefore biopsy may be needed in long-term treatment [V. Amiodarone] - Can cause same histology and clinical outcome as alcoholic hepatitis A. [Cholelithiasis] **Pathogenesis:** - Imbalance of cholesterol and its solubilizing agents, bile salts and lecithin concentrations - If hepatic cholesterol secretion is excessive then bile salts and lecithin are "overloaded", supersaturated cholesterol precipitates and can form gallstones **Types of Stones:** \- Cholesterol (80%) = mixed (\>70% cholesterol by weight), radiolucent - Risk factors: - Female, fat, fertile, forties - North American First Nations People have highest Incidence - Diabetes Mellitus (DM), Pancreatitis

Use Quizgecko on...
Browser
Browser