Module 7 Outline: Pathophysiology PDF

PATHOPHYSIOLOGY MODULE 7 OUTLINE o hepatomegaly plus RUQ pain o splenomegaly and cervical I. Hepatobiliary Tree Disorders lymphadenopathy (10-...

PATHOPHYSIOLOGY MODULE 7 OUTLINE o hepatomegaly plus RUQ pain o splenomegaly and cervical I. Hepatobiliary Tree Disorders lymphadenopathy (10-20% of cases) a. Hepatitis i. Viral - hepatic enzymes ii. Drug – induced o hepatocellular necrosis which causes b. Cholelithiasis increased AST, ALT > 10-20X normal c. Cholecystitis o ALP and bilirubin minimally i. Acute increased ii. Chronic o WBC normal or slightly decreased II. Disorders of the Stomach initially, a. Gastritis i. Peptic Ulcer Disease Viral Hepatitis - (A&E=Acute, B&D=Acute & ii. H. Pylori associated Chronic, C=Chronic) III. Disorders of the Pancreas a. Acute Pancreatitis a. HEPATITIS A VIRUS (Acute): IV. Disorders of the Intestines Etiology a. Gastroenteritis - Hepatitis A Virus (Most Common Viral i. Bacterial Hepatitis Worldwide) ii. Viral b. Constipation Pathogenesis: V. Parasitic Gut Infections - Fecal-Oral Transmission - 2-6wk Incubation I. HEPATOBILIARY TREE DISORDERS - Virus is Directly Cytopathic to the Liver - But Does NOT lead to Cirrhosis a. Hepatitis - liver inflammation Clinical Features: Etiology - Acute Symptoms ONLY; No Chronic. - viral infection - Viremia > Fever, Malaise, Anorexia, Nausea, - toxins Arthralgia - drugs Signs: - other (immune mediated - Jaundice (After 1-2wks) (Due to Intrahepatic Cholestasis) i. Viral Hepatitis o Inc Conjugated Bilirubin ▪ > Pale Stools ACUTE VIRAL HEPATITIS ▪ > Dark Urine Definition - +/- Hepatomegaly - viral hepatitis lasting < 6 months - +/- Splenomegaly - +/- Tender Lymphadenopathy Clinical Features - Rarely - Hepatic Encephalopathy & Death. - most are subclinical - prodrome (flu-like illness) may precede Investigations jaundice by 1-2 weeks - LFTs - (Everything Raised) - nausea, vomiting, anorexia, taste/smell - Hep A Serology disturbance (aversion to cigarettes) - Hep A PCR headaches, fatigue, malaise, myalgias - low-grade fever may be present Prognosis arthralgia and urticaria (especially hepatitis - Usually Self-Limiting with Supportive B) Treatment Only. - clinical jaundice (icteric) phase (50% of b. HEPATITS E VIRUS (Acute): cases) lasting days to weeks - (Very Similar to Hep A; But HIGH MORTALITY in PREGNANCY [20% > DIC in o pale stools and dark urine 1-5 days 3rd Trimester]) prior to icteric phase [MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD 1  PATHOPHYSIOLOGY - Both HBsAg and HBeAg are present during Etiology acute hepatitis B - Hepatitis E Virus (A Herpesvirus) - Anti-HBs follows HBsAg clearance and confers long-term immunity Pathogenesis - Anti-HBe and anti-HBc appear during the - Virus is Directly Cytopathic to the Liver acute and chronic phases of the illness but Clinical Features do not provide immunity! - Fecal-Oral Transmission (Incl. Vectors: - Anti - HBe indicates low infectivity Dogs/Pigs/Rodents) Clinical Picture - (Same as Hep A) Prevention - HBV vaccine = recombinant HBsAg Investigations - Seroconversion rates about 94% after 3 - LFTs ʹ (Everything Raised) injections - Hep E Serology - Hepatitis B immune globulin (HBIG) = anti- - Hep E PCR HBs o for needle stick, sexual contact, and Prognosis neonates born to mothers with - 1-2% Mortality (From Fulminant Hepatic acute or chronic infection Failure) - 20% Mortality in Pregnancy (From DIC in b. HEPATITIS C VIRUS (HCV) 3rd Trimester) - Transmission is chiefly parenteral o Transfusions (HCV is the most ACUTE AND CHRONIC VIRAL HEPATITIS common cause of post-transfusion hepatitis) a. HEPATITIS B VIRUS (HBV) o IV drugs use - transmission via parenteral route or o Sexual transmission occurs but risk is equivalent less than with HBV - vertical transmission o 40% of cases have no risk factors o occurs during 3rd trimester or early - Clinical incubation period 5-10 weeks post-partum - AST and ALT levels fluctuate (unlike Hep A o HBsAg +ve, HBeAg +ve mothers ––> or B) 90% of infants infected - More than half progress to chronic liver o HBsAg +ve, anti-HBe +ve mothers –– disease (see below) > 10-15% infected - Serology o give HBIG and full HBV vaccination o HCV RNA (detected by PCR assay) to newborns of HBsAg +ve mothers o anti-HCV (90% effective) o develops in 6-8 weeks in 85% of - incubation period 6 weeks to 6 months patients - infectivity: during HBsAg positivity o persists in chronic infection and - high-risk groups does not confer immunity o neonates of carriers (“vertical transmission”) Prevention: no accepted vaccine for HCV o partners of acutely and chronically infected individuals, with male c. HEPATITIS D (HDV) homosexuals at particular risk - infectious only in the presence of HBV o IV drug users because HBV surface antigens are required o hospital employees for replication o patients from endemic country - 2 patterns of transmission Hepatitis B serology (Refer to PowerPoint) o nonparenteral transmission by close - HBsAg: surface antigen personal contact in endemic areas - HBeAg: e antigen (a component of HBV (Mediterranean) core); marker of viral replication o transmission by blood products in - HBcAg: core antigen (cannot be measured non-endemic areas (IV drugs, blood in serum) transfusions) - Types of infection [MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD 2  PATHOPHYSIOLOGY o coinfection: simultaneous HBV and - Blood levels of acetaminophen correlate HDV infection with the severity of hepatic injury o superinfection: appears as clinical - Therapy exacerbation in a chronic HBV o Gastric lavage/emesis (if < 2 hrs patient after ingestion) - predisposes to severe or fulminant course o Oral charcoal - Serology: HBsAg, anti-HDV IgM or anti-HDV o N-acetylcysteine PO/IV within 8-10 IgG hours of ingestion, most effective for up to 72 hours (promotes Prevention: HBV vaccine hepatic glutathione synthesis) d. HEPATITIS E VIRUS (HEV) II. Chlorpromazine - fecal-oral transmission occurring in - Cholestasis in 1% after 4 weeks; often with epidemics in Asia, Africa, Central America fever, rash, jaundice, pruritus and - most have mild disease, but in 3rd trimester eosinophilia of pregnancy 10-20% have fulminant liver failure III. INH - serology: anti-HEV - 20% develop elevated transaminases but < 1% develop clinically significant disease Prevention: no vaccine available - susceptibility to injury increases with age IV. Methotrexate ii. Drug induced liver disease / Drug induced - May rarely cause cirrhosis, especially in the hepatitis presence of obesity, diabetes, alcoholism - Scarring develops without symptoms or SPECIFIC DRUGS changes in liver enzymes, therefore biopsy may be needed in long-term treatment I. Acetaminophen - metabolized by hepatic cytochrome P450 V. Amiodarone system - can cause fulminant hepatic failure - can cause same histology and clinical (transaminases > 1,000 U/L) outcome as alcoholic hepatitis - requires 10-15g in normals, 4-6g in alcoholics/anticonvulsant users b. Cholelithiasis - Mechanism: o high acetaminophen dose saturates Pathogenesis glucuronidation and sulfation - Imbalance of cholesterol and its solubilizing elimination pathways, therefore a agents, bile salts and lecithin concentrations reactive metabolite is formed which - If hepatic cholesterol secretion is excessive covalently binds to hepatocyte then bile salts and lecithin are membrane “overloaded”, supersaturated cholesterol - Presentation precipitates and can form gallstones o first 24 hrs.: nausea and vomiting usually within 4-12 hours Types of Stones o next 24-48 hrs.: hepatic necrosis - Cholesterol (80%) = mixed (> 70% resulting in increased cholesterol by weight), radiolucent aminotransferases, jaundice, o risk factors possibly hepatic encephalopathy, ▪ female, fat, fertile, forties acute renal failure, death ▪ North American First Nations o after 48 hrs: continue hepatic peoples have highest necrosis/resolution incidence o note: potential delay in presentation ▪ diabetes mellitus (DM), in sustained-release products pancreatitis [MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD 3  PATHOPHYSIOLOGY ▪ malabsorption, terminal ileal - Systemic signs – low grade fever (>38.5 resection or disease (e.g. degC); tachycardia inflammatory bowel diseases - Focal peritoneal findings - Pigment stones (20%), may be radio- o Murphy's sign (sudden cessation of opaque inspiration with deep RUQ o smooth green/black to brown: palpation) ▪ composed of unconjugated - Palpable gallbladder in one third of patients bilirubin, calcium, bile acids o black pigment stones Differential diagnosis ▪ associated with cirrhosis, - Perforated or penetrating peptic ulcer, MI, chronic hemolytic states pancreatitis, hiatus hernia, right lower lobe o calcium bilirubinate stones pneumonia, appendicitis, hepatitis, herpes associated with bile zoster stasis, (biliary strictures, dilatation Diagnostic investigation and biliary infection - elevated WBC, left shift (Clonorchis sinensis) - mildly elevated bilirubin, ALP Natural History - sometimes slight elevation AST, ALT - 80% are asymptomatic - U/S shows distended, edematous - 18% develop symptoms over 15 years gallbladder, pericholecystic fluid, large stone stuck in gallbladder neck, sonographic Clinical Presentation (in severity of increasing Murphy's sign (maximum tenderness order) elicited by probe over site of gallbladder) - asymptomatic stones o most asymptomatic gallstones do II. DISORDERS OF THE STOMACH NOT require treatment a. Gastritis o consider operating if calcified "porcelain" gallbladder, sickle cell GASTRITIS: disease (15-20% associated cancer), - Inflammation of the Stomach Lining DM, history of biliary pancreatitis Etiology & Pathogenesis - biliary colic - Acute: - cholecystitis - acute and chronic o 15% Alcohol - complications of cholecystitis o NSAIDs > Inhibits COX > dec - choledocholithiasis (CBD stones) Prosƚaglandin > Hyperacidity > - cholangitis Inflammation - biliary induced pancreatitis o Severe Burns > dec Plasma Volume > - biliary induced ileus Sloughing of Stomach Mucosa - Chronic: c. Cholecystitis o **80% Bacterial - Helicobacter Pylori (Most Common) A. ACUTE CHOLECYSTITIS - Atrophic: o Autoimmune ʹPernicious Anemia ʹ Mechanism (Antibodies against Parietal Cell & IF - Inflammation of gallbladder resulting from > B12 Deficient) sustained obstruction of cystic duct by gallstone (80%) Clinical Features: - No cholelithiasis in 20% (acalculous) - Symptoms: o Abdo Pain, Dyspepsia, Bloating, Nausea/Vomiting, +/- Hematemesis Signs and symptoms (if PUD), +/- Anemia (If Pernicious - Often have history of biliary colic B12 Deficiency) - Severe constant epigastric or RUQ pain – - Anorexia, nausea and vomiting are common [MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD 4  PATHOPHYSIOLOGY Investigations: Treatment: - **C13 Urea Breath Test - (H.Pylori) - Conservative - (Avoid Precipitating Factors - Serology (IgG) - (H.Pylori) (Alcohol/NSAIDs) - H.pylori Fecal Antigen Test - (H.Pylori) - Antacids - Endoscopy + Gastric Biopsy - (H.Pylori - PPIs - (Omeprazole) or H2-Antagonists - Microscopy + ?Gastric Cancer) (Ranitidine) - H. Pylori Triple Eradication Therapy ʹ Treatment: (Clarithromycin + Amoxicillin +/- - Conservative Metronidazole) o (Avoid Precipitating Factors - *Emergency Surgery ʹ (If Hematemesis / (Alcohol/NSAIDs)) Rupture / Peritonitis / CANCER o Antacids o PPIs - (Omeprazole) or H2- Complications: Antagonists - (Ranitidine) - GI Bleeding > Anemia o H.Pylori Triple Eradication Therapy - Perforation > Hemorrhage/Shock, ▪ (Clarythromycin + Amoxicillin Peritonitis, or Into Pancreatitis. +/- Metronidazole) - Pyloric Stenosis (Scarring) > Gastric Outlet o If Pernicious ʹ (B12 Injections) Obstruction > Vomiting - **GASTRIC CANCER (NB: H. Pylori > 6x Risk PEPTIC ULCER DISEASE: of Cancer) Etiology: Either - inc. Attack (Hyperacidity, Zollinger Ellison III. DISORDER OF THE PANCREAS Syndrome) Or - dec Defense (**H.Pylori, Stress, Drugs a. ACUTE PANCREATITIS: [NSAIDs & Corticosteroids], Smoking) Etiology: - 50% - Gallstones (Cholelithiasis) > Morphology: Ampulla/Common Bile Duct Obstruction - Small, Single, Round, Punched out Ulcer - 40% - Alcohol Abuse - 90% in Duodenum or Lesser-Curve of - 10% Infections/Metabolic (inc. Ca in Stomach. hyperparathyroidism) DKA͕, Uremia͕ - Healing Peptic Ulcers have Radiating Pregnancy/ Trauma/ Ischemia /Duodenal Mucosal Folds due to scar contraction. Ulcer/Scorpion Venom/Drugs/Unidentified Clinical Features: Pathogenesis: - Burning Epigastric Pain; (Most Severe when - Autodigestion of Pancreas > Reversible Hungry. Relieved by Food) Inflammation > +/- Necrosis - Nausea & Vomiting - Can lead to Systemic Inflammatory - Anorexia & Weight Loss Response Syndrome - Hematemesis/Melena o > Shock - (Perforation > Acute Peritonitis) o > Acute Renal Failure o > Acute Respiratory Distress Investigation: Syndrome - Clinical History Clinical Features: - Endoscopy + Biopsy (Ulcer? H. Pylori? - An Acute Medical Emergency: Gastric Cancer?) - Signs/Symptoms: - **C13 Urea Breath Test - (H. Pylori? The o Epigastric/Abdo Pain Best NON-Invasive Diagnosis) o Precipitated by Large Meal OR - Serology (IgG) - (H. pylori) Alcohol - H. Pylori Fecal Antigen Test - (H.pylori) o Peritonitis - (Guarding + Rigidity) o Vomiting o If Hemorrhage > Hypotension & Shock > Grey Turner’s and Cullen sign o Local Complications: [MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD 5  PATHOPHYSIOLOGY ▪ Pancreatic Abscess/Infection - Stool OCP if worried. ▪ Pseudocysts ▪ Duodenal Obstruction Treatment: - Supportive Treatment - (Fluid & Electrolyte o Systemic Complications: Replacement) ▪ Jaundice - Anti-Diarrheal Controversial > Symptomatic ▪ DIC (Diss.Iv.Coag) but decreases toxin expulsion ▪ ARDS (Resp. Distress) ▪ Acute Renal Failure 2. ESCHERICHIA COLI – (“TRAVELLER’S DIARRHEA”): Diagnosis: - Rule out Other Causes of Acute Abdomen͟ - ETEC: (Enterotoxigenic E. coli) o Appendix/#Diverticulitis/#Peptic o Produces Toxins: Ulcer/#Cholecystitis/Isch.Bowel/ o Travelers Diarrhea Bowel Obstruction. - EIEC: (Enteroinvasive E. coli) - Inc Serum Amylase (Within 24hrs) o Active Intestinal - Inc Serum Lipase (After 72hrs/3days) Invasion/Destruction - CBC - Neutrophil Leukocytosis o Traveller͛s Dysentery - Inc Alkaline Phosphatase ;If Biliary StasisͿ - Inc Bilirubin - EPEC: (Enteropathogenic E. coli) - (ERCP/MRCP if Indicated) o Sporadic disease in babies and - !!NOT Biopsy!!! ʹ HAZARDOUS children Prognosis: - EHEC: (Entero-Hemorrhagic E. coli) - 80% - Self-Limiting with Supportive o The Serious One: Treatment o Produce Verotoxin > Destroys - 20% - Life Threatening & 1/More-Organ Platelets & RBCs > HEMOLYTIC- Failure (Requires ICU) UREMIC SYNDROME > Kidney Failure + Bleeding + Dysentery IV. DISORDERS OF THE INTESTINES 3. SALMONELLA; TYPHOID͟ Etiology: a. GASTROENTERITIS - Salmonella typhi: (Bacterial Gastroenteritis) (Food Poisoning): Pathogenesis: - > Dysentery 1. TOXIGENIC DIARRHEA (FOOD POISONING): - Can cause Septicemia - Also, Fever - rose spots - delirium - Etiology: perforation of bowel - Staph Aureus (Poor Food Handling) Management: - Bacillus Cereus (Mostly found in cereal - Ceftriaxone +/- Ciprofloxacin Symptoms: 4. LISTERIOSIS (LISTERIA): - Onset Within 4hrs Etiology: o *Vomiting, *Stomach Cramps, - Listeria Monocytogenes – (G-Pos) Diarrhea - (Soft Cheeses & Cold Deli Meats) Pathogenesis: - Toxigenic Diarrhea Risk to Pregnant Women & Immunocompromised - (NB: Some toxins are Heat Stable) 5. CHOLERA: Diagnosis: Etiology: Vibrio Cholerae - History + Clinical Course Symptoms: Profuse Rice-Water Stools o - Retrospective Epidemiology > Find Common Management: Denominator. (Who ate what??) - Fluid Replacement o Prognosis: Self-Limiting [MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD 6  PATHOPHYSIOLOGY o Medication side effects NB: DYSENTERIC ORGANISMS: o Salmonella, (antidepressants, codeine) Shigella, Entamoeba Histolytica o Left sided colon cancer (consider in older patients) Viral o Metabolic ▪ DM Etiology: ▪ Hyperthyroidism - 80% Norovirus (Adult Diarrhea) ▪ Hypercalcemia - Rotavirus (Kid Diarrhea Gastroenteritis ▪ Parkinson’s disease - Produces ͚Toxic Rotavirus Protein͛ - NSP4 > ▪ Multiple sclerosis Induces Chloride Secretion > Inhibits Water Investigations: Absorption in gut - Swallow radio opaque markers to quantitate colonic transit time (normal: 70 Clinical Features: hours) - Timeframe: Treatment: (in increasing order of potency) o Incubation Period = 2 days - Surface acting (soften and lubricate) o Duration of Symptoms = 6 days o Docusate salts and mineral oils o Still infective for = 2 days after - Bulk forming symptoms subside. o Bran, psyllium seeds - Any kid with vomiting/diarrhea should stay - Osmotic agents home for >1wk to minimize transmission o Lactulose, sorbitol, magnesium citrate, magnesium sulfate, Symptoms: magnesium hydroxide, sodium - Vomiting (projectile) phosphate - Diarrhea - Cathartics - + Flu-Like Illness - (Fever, Irritability, Poor o Castor oil, senna (watch out for Feeding, Myalgia) melanosis coli) Diagnosis: V. PARASITIC GUT INFECTIONS - Clinical Diagnosis of Gastroenteritis - Definitive Diagnosis via Stool Sample PARASITIC GUT INFECTIONS o Enzyme Immunoassay (Protozoa & Helminths): o Or RT-PCR Management: Transmission: - Supportive Mx - Fecal-Oral - (Ingestion of Dormant Cysts in - FLUID REPLACEMENT! Contaminated Food/Water) - Quarantine (Especially for Immunocompromised/Chemo Pts!) Diagnosis: - Stool Samples (Looking for cysts) under b. Constipation Direct Microscopy - Antigen Testing - The passage of infrequent or hard stools with straining ( Malabsorption a. Strongyloides stercoralis (threadworm) Diagnosis: b. Ancylostoma duodenale (hookworm) - - Cysts in Stools Complications: Management: - Chronic Infection - Albendazole - Malabsorption o > Malnutrition ********END OF MODULE 7******** o > Fatty Stools Treatment: - Metronidazole b. CRYPTOSPORIDIUM: Transmission: - Ingestion of oocysts (Contaminated Drinking Water/Public Pools) - Can survive Chlorination Pathogenesis is mostly unknown. - Possibly induces inflammatory response > Disrupts absorptive surface - Damages Villi > Crypt Cells Replicate faster to replace them > Immature cells in the villus > Poor absorption. Treatment: - Nitazoxanide (Normally Self-Limiting if Immunocompetent) Long term Effects: - AIDS PATIENTS DO NOT RECOVER > Chronic Infection Diagnosis: - Cysts in Stools c. ENTAMOEBA HISTOLYTICA (The Amoebic Dysentery): Transmission: - Ingestion of oocysts (Fecal Oral) Pathogenesis: - Intestinal Invasions > Ulcerations > Dysentery (Bloody Diarrhea) Diagnosis: - Cysts in Stools Management: - Metronidazole HELMINTHIC INFECTIONS - clinically significant helminths are “soil transmitted” [MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD 8