Multiple Organ Dysfunction Syndrome PDF

MULTIPLE ORGAN DYSFUNCTION SYNDROME (MODS) Marcela Lizarraga, MHS, PA(ASCP)CM, PhD. 1 OBJECTIVES Define MODS, sepsis and SIRS Propose how MODS, sepsis and SIRS relate to each other Explain the etiology of sepsis and shock Describe the mac...

MULTIPLE ORGAN DYSFUNCTION SYNDROME (MODS) Marcela Lizarraga, MHS, PA(ASCP)CM, PhD. 1 OBJECTIVES Define MODS, sepsis and SIRS Propose how MODS, sepsis and SIRS relate to each other Explain the etiology of sepsis and shock Describe the macroscopic and microscopic findings in sepsis and shock Propose how you would prepare for an autopsy case with suspected sepsis and shock Explain the findings of MODS, sepsis and shock in cases of: Bronchopneumonia Infective endocarditis Clostridium enterocolitis Viral hepatitis Urosepsis Explain MODS in the setting of neoplasia-associated death Explain MODS in the setting of paraneoplastic effect 2 CHAPTER 13 QUOTE… Some [microorganisms] will get into our deepest tissues and set forth in the blood, but it is our response to their presence that makes the disease. Our arsenals for fighting off bacteria are so powerful, and involve so many different defense mechanisms, that we are in more danger from them than from the invaders. LEWIS THOMAS, 19721 3 MULTIPLE ORGAN DYSFUNCTION Multiple organ dysfunction syndrome (MODS) is an acute (develops rapidly) and serious illness in which two or more organ systems stop working as they should.  Trauma  Infection/Sepsis  Disease 4 SEPSIS AND SHOCK - TERMINOLOGY Important abbreviations  Systemic inflammatory response syndrome (SIRS)  Multiple organ dysfunction syndrome (MODS)  Synonyms = MODS: Multi-organ failure, multiple systems organ failure Definitions  Shock: Inability to meet cellular metabolic requirements due to global hypoperfusion from inadequate circulating blood or plasma volume  MODS: Physiologic dysfunction of ≥ 2 organ or physiologic systems not directly related to primary cause of shock  e.g., acute tubular injury and coagulopathy following cardiogenic shock due to acute myocardial infarction  SIRS: Systemic activation of innate immune response, regardless of cause, clinically manifested as 2 or more of the following  Temperature > 38°C or < 36°C; heart rate (HR) > 90 beats/min; hyperventilation (respiratory rate > 20 breaths/min or PaCO2 < 32mmHg); white blood cell (WBC) count > 12,000/μL or < 4,000/μL or 10% bands  Sepsis: Probable or documented infection plus SIRS manifestations  Severe sepsis: Sepsis plus infection-induced organ dysfunction, tissue hypoperfusion, or hypotension  Organ dysfunction: Altered mental status, generalized edema, acute lung injury, acute renal injury, oliguria, edema, coagulopathy, hyperbilirubinemia, hyperglycemia, ileus, thrombocytopenia  Tissue hypoperfusion: Lactate > 1mmol/L, ↓ capillary refill, or mottling  Hypotension: Systolic blood pressure (BP) < 90mmHg or mean arterial pressure < 70mmHg  Septic shock: Sepsis plus hypotension persisting despite administration of adequate fluid resuscitation  Stigmata of shock: Nonspecific pathologic findings reflecting pattern of organ injury due to tissue hypoperfusion 5 6 SEPSIS AND SHOCK - ETIOLOGY Causes of Shock  Hypovolemic: Massive loss of blood or plasma volume  e.g., hemorrhage, burns, massive vomiting or diarrhea, anaphylaxis  Cardiogenic: Inability of heart to pump blood due to intrinsic failure (e.g., infarction, arrhythmia, cardiomyopathy) or external factors (e.g., cardiac tamponade, pulmonary embolism, tension pneumothorax) Pathogenesis of Shock  Initial phase: ↓ tissue perfusion → sympathetic nervous system activation → ↑ HR, ↑ myocardial contractility, ↑ arterial & venous tone; activation of renin-angiotensin system → BP maintained with blood preferentially shunted to heart & brain  Progressive phase: ↓ BP & tissue perfusion → global tissue hypoxia, ↑ lactic acid, ↓ pH → arteriolar dilation, venous constriction, ↑ capillary permeability → loss of intravascular volume → organ dysfunction  Irreversible phase: Refractory hypotension, multiple system organ failure, and death Causes of SIRS  Overwhelming microbial infection or release of microbial toxins  Deaths due to sepsis: Gram negative bacteria > Gram positive bacteria > fungal >> opportunistic bacteria & fungi, viruses  Tissue injury: Massive trauma, severe burns, surgery, ischemia/reperfusion injury, transplant rejection, pancreatitis, erythroderma  Metabolic: Thyroid storm, acute adrenal insufficiency  Therapy related: Blood products, granulocyte-macrophage colony-stimulating factor, anesthesia-related malignant hyperpyrexia, neuroleptic malignant syndrome, opiates, benzodiazepines  Malignancy: Lymphoma, tumor lysis syndrome  Neurologic: Subarachnoid hemorrhage 7 SEPSIS AND SHOCK - ETIOLOGY Predisposing Factors to SIRS  Inherited or acquired defects in innate or adaptive immune system  Age (↑ risk neonates & elderly) Pathogenesis of SIRS  Systemic activation of innate immune response  Activation of neutrophils, monocytes/macrophages, & endothelium  Early phase: Excessive pro-inflammatory cytokines release → vasodilation, edema  Late phase: Diminished innate immune function → diminished adaptive immune function  Pro-oxidant state: ↑ reactive oxygen & nitrogen species, ↓ free radical scavengers → vasodilation, edema  Pro-coagulation state: Complement, coagulation cascade, & endothelial activation → disseminated intravascular coagulation (DIC)  → metabolic derangements, organ dysfunction, and shock 8 SEPSIS AND SHOCK – CLINICAL ISSUES Epidemiology  SIRS: Most critically ill patients are at highest risk  Sepsis: Most common cause of death in noncoronary intensive care unit (ICU)  600,000 cases annually in USA  Incidence and number of deaths increasing in USA and worldwide Presentation  Shock: Varies with etiology; most common clinical manifestations are hypotension, tachycardia, cyanosis, and evidence of organ dysfunction  Sepsis: Most common primary sites of infection (in ↓ frequency) are lung, bloodstream, abdomen, skin and soft tissue, urinary tract, and central nervous system Treatment  Shock: Identify and treat underlying cause  Sepsis: Supportive therapy only Prognosis  Mortality rate of shock: Varies according to severity and etiology  Mortality rate of sepsis:  Average: 20-30%; range: 5-50%  Varies according to predisposing factors, degree of organ dysfunction, type and site of infectious agent Clinical Organ Dysfunction Scoring Systems  Commonly used scoring systems for assessing severity of illness and predicting mortality in ICU patients  General prognostication scores: Acute physiology and chronic health evaluation (APACHE), simplified acute physiology score (SAPS), mortality probability models (MPM)  Organ dysfunction scores: Sequential organ failure assessment (SOFA), multiple organ dysfunction score (MODS), logistic organ dysfunction system (LODS) 9 SEPSIS AND SHOCK – IMAGING FINDINGS  Radiographic Findings  Lungs: Diffuse bilateral infiltrates (“white out”)  Ultrasonographic Findings  Heart: Systolic and diastolic ventricular dysfunction  Low ejection fraction is predictor of mortality in septic shock  CT Findings  Brain: Hypodensities in bilateral watershed areas progressing to whole brain edema  Other: Evidence of specific underlying cause of shock &/or sepsis 10 SEPSIS AND SHOCK – MACROSCOPIC FINDINGS External Examination  Extensive petechia &/or ecchymoses  Pallor of conjunctiva &/or nailbeds  Cyanosis of distal extremities  Severe peripheral edema  Jaundice Internal Examination  Evidence of specific cause of shock such as massive acute myocardial infarction, gastrointestinal hemorrhage, perforated viscus with fecopurulent exudate  Macroscopic stigmata of shock  Soft tissue edema &/or hemorrhage  Serous effusions  Brain: Diffuse cerebral swelling ± uncal or cerebellar herniation  Lungs: Firm, heavy, wet ± hemorrhage, frothy fluid within airways  Heart: Epicardial &/or endocardial petechia, acute subendocardial ischemia  Liver: Mottled cut surface (“nutmeg” appearance)  Pancreas: Fat saponification  Gastrointestinal tract: Serosal and mucosal petechia, mucosal erosions  Kidneys: Cortical pallor with medullary congestion 11 SEPSIS AND SHOCK - MICROSCOPIC Histologic Features  Shock: Diffuse vascular congestion, hemorrhage, fibrin thrombi of microvasculature involving any organ system  Sepsis: Evidence of primary infection (e.g., acute bronchopneumonia, meningitis), septic emboli to any organ (highly specific), widespread bacterial overgrowth disproportional to postmortem interval Organ Examination  Microscopic stigmata of shock  Brain: Hypoxic nerve cell change, cerebritis (sepsis)  Heart: Subendocardial ischemia (demand ischemia)  Lungs: Alveolar edema, capillary congestion, diffuse alveolar damage  Liver: Centrolobular hemorrhagic necrosis, canalicular or ductal cholestasis, steatosis  Gastrointestinal tract: Submucosal hemorrhages, erosions, or ulcerations  Kidneys: Acute tubular necrosis, pigmented casts (hemoglobin, myoglobin, or bile)  Spleen: Acute splenitis, congestion  Bone marrow: Reactive hypercellularity  Adrenal glands: Cortical cell lipid depletion, microscopic foci of hemorrhage within cortex 12 SEPSIS AND SHOCK – ANCILLARY TESTS Histochemistry  GMS (Gomori methenamine silver)  Gram Laboratory Tests  Supporting evidence of organ dysfunction (if antemortem samples not available)  e.g., troponin level, CBC, chemistry panel  Postmortem blood cultures: High false positive rate due to agonal bacteremia, postmortem bacterial transmigration  Positive postmortem blood cultures should correlate with gross and histologic evidence of infection Specialty Consultation  Centers for Disease Control and Prevention Infectious Diseases Pathology Branch  Provides important information and guidelines related to transport of pathology materials and clinical samples for ancillary testing 13 SEPSIS SIGNS Hemorrhage Bacterial endocarditis Colon hemorrhage 14 SEPSIS SIGNS “Nutmeg” liver Peritonitis Infected PEG line 15 BRONCHOPNEUMONIA Terminology  Pathologic definition of bronchopneumonia based on anatomic distribution of acute inflammatory changes  Distribution can be appreciated grossly as patchy foci of airway-centered consolidation with intervening areas of normal lung parenchyma (lobular distribution)  Lobular pattern is in contrast to lobar pneumonia (consolidation of an entire lobe)  Pneumonia is classified by specific etiologic agent Etiology  Most often result of inhalation of microorganisms or aspiration  A preceding viral pneumonia increases susceptibility to secondary infection (bronchopneumonia)  Nosocomial pneumonia is leading cause of death from hospital-acquired infection  Gram-negative organisms predominate in ICU-acquired infections and ventilator-associated pneumonia Macroscopic Pathology  May involve 1 or multiple lobes and is frequently bilateral  Most pronounced changes often in basilar regions Microscopic Pathology  Airway-centered acute inflammation with contiguous involvement of peribronchial/peribronchiolar alveolated parenchyma  Focal or extensive organization may be present 16 INFECTIVE ENDOCARDITIS Terminology = Infective endocarditis: Inflammation of endocardium (typically refers to infections on valve surfaces) Etiology  Staphylococcus aureus (31%), Streptococcus viridans (17%)  Microbe portal of entry  Intravenous drug abuse, dental procedure  Valve surface damage  Degenerative, rheumatic, congenital  Clinical Issues  3-10 episodes per 100,000 person-years  Mean age: 51-65 years  M > F (1.2-2.5:1)  Hospital mortality rate 9.6-26% Macroscopic Pathology  Vegetations  Fleshy, soft, clot-like, friable  Septic emboli and infarcts (brain, spleen, kidneys, liver) Microscopic Pathology  Vegetations  Acute: Fibrin, platelets, neutrophils, microorganisms  Subacute: Granulation tissue, fibroblasts, collagen, plasma cells, absent microbes  Valve annulus abscess  Myocardial abscess 17 CLOSTRIDIUM DIFFICILE ENTEROCOLITIS Etiology  Altered gut flora → colonization (usually nosocomial), fecal-oral  Host factors + organism virulence → disease  Disease due to effects of toxins A and B  A: Enterotoxin: Marked fluid exudation from bowel  B: Cytotoxin: Affects actin polymerization Macroscopic Pathology  Changes due to prolonged severe diarrhea, colitis, and protein-losing enteropathy  Dehydration changes (skin tenting, sunken eyes), raw-appearing anal tissue with possible tissue breakdown, often with decubitus ulcer  Distended abdomen  Generalized edema (anasarca) Microscopic Pathology  Patchy process involving clusters of crypts surrounded by normal-appearing mucosa  Dilated crypt erupts into bowel lumen as pseudomembrane  Epithelial cells lining involved crypts are necrotic  Inflammation is superficial in crypts and pseudomembrane  Pseudomembrane composed of mucus, neutrophils, fibrin and necrotic epithelium  Severe disease has mucosal necrosis and deep mural inflammation  Other organ changes  Sepsis-related acute tubular injury, patchy hepatic necrosis 18 VIRAL HEPATITIS Etiology  Hepatotropic viruses: Hepatitis A, B, C, D, and E  Herpes virus group: HSV, CMV, EBV, VZV, HHV-6  Viral hemorrhagic fevers: Yellow fever, dengue fever, Ebola, hantavirus, etc. Clinical Issues  Important elements of chart review: Travel, food consumption, and sexual history, history of injection drug use, blood transfusions, tattoos/piercings, blood/body fluid exposures, immunosuppression Macroscopic Pathology  Acute hepatitis: Hepatomegaly, cholestasis, necrosis, regenerative nodules, hemorrhage  Chronic hepatitis: Hepatomegaly or atrophy, cirrhosis, masses Microscopic Pathology  Acute hepatitis (HAV, HBV ± HDV, HCV, HEV): Lobular inflammation, acidophil bodies, variable necrosis, swollen hepatocytes, lobular disarray, cholestasis, variable portal inflammation  Chronic hepatitis (HBV ± HDV, HCV, rarely HEV): Portal inflammation, variable interface and lobular activity, fibrosis, cirrhosis, ± siderosis, dysplastic nodules, hepatocellular carcinoma  Reporting Considerations  Final report should include: Type of viral hepatitis, extent of hepatic disease, associated extrahepatic findings, whether the virus was the cause of death or a contributing factor 19 UROSEPSIS  Urosepsis is defined as SIRS in the setting of complicated urinary tract infection  Accounts for 25% of all cases of sepsis  Certain groups are at increased risk of urosepsis  Patients with abnormal urinary tract anatomy  Patients with urinary tract catheters/hardware or history of urinary tract procedure  Patients with certain underlying conditions: Diabetes, sickle cell, neurogenic bladder  Usually the result of ascending infection  Most often gram-negative enteric bacteria  Enterococci: In institutional settings in catheterized patients  Secondary involvement of urinary tract by bloodstream infection is less common  Typically, Staphylococcus aureus  Urinary tract findings  Obstructive lesions: Extrinsic tumors, prostatic enlargement, bladder distension and trabeculation, hydroureter, hydronephrosis  Inflammatory urinary tract changes: Cystitis, pyelonephritis, renal abscess  Findings associated with sepsis  Changes of disseminated intravascular coagulation: Petechiae, ecchymoses, microthrombi  Anasarca, effusions  Diffuse alveolar damage  Changes of septic organ injury and failure 20  NEOPLASIA- ASSOCIATED DEATH  Paraneoplastic syndromes (PNS) are systemic effects of tumors not due to metastatic disease  2 main mechanisms for PNS: Secreted tumor product and immunologic cross-reactivity between tumor and normal tissues  Tumor lysis syndrome: Metabolic derangement usually seen 48-72 hours after initial treatment due to massive lysis of lymphoma/leukemia cells  Graft-vs.-host disease (GVHD): Immune-mediated disease following allogeneic stem cell transplantation  3 criteria for GVHD to occur: Immune competent graft, disparate (nonidentical) recipient, immunocompromised recipient  Manifestations of thrombophilia in malignancy  Trousseaus syndrome: Often associated with pancreatic adenocarcinoma and other mucinous adenocarcinomas  Venous thromboembolism  Nonbacterial thrombotic endocarditis (NBTE): Sterile thrombi usually along closing edge of valves; can embolize (marantic endocarditis)  Thrombotic microangiopathy (TMA): Usually related to cancer therapy 21 DEATH DUE TO PARANEOPLASTIC EFFECT Paraneoplastic syndromes are remote effects of tumors, not related to invasion, metastasis, or obstruction  Typically produced by 1 of 2 mechanisms  Tumor-elaborated substance (hormones, cytokines, enzymes, etc.)  Cross-reacting antitumor antibodies (especially in neuromuscular paraneoplastic syndromes)  Clinical syndrome of a paraneoplastic syndrome may present before or after diagnosis of underlying tumor  Demonstration of paraneoplastic syndromes may be challenging  Occur in an estimated 1-20% of cases of malignant tumors  Tumors may be occult and small  Clinical presentations are often nonspecific and may be seen unassociated with tumors  Clinicopathologic correlation is essential  Review clinical records, including laboratory and imaging results, carefully  Perform a diligent external examination  Perform a thorough gross and histologic examination  Sample thoroughly for histology  Almost any tumor may be associated, but most common are lung (especially small cell carcinoma), hematolymphoid, kidney, breast, and ovary 22 PARANEOPLASTIC SIGNS Lester-Trelat sign Scleroderma Melanosis cutis 23 THANK YOU 1. Autopsy Pathology: A Manual and Atlas (13, 16) 2. Handbook of Autopsy Practice () 3. DiMaio’s Forensic Pathology () 4. Handbook of Pediatric Autopsy Pathology () 5. Forensic Pathology Review () 6. The Hospital Autopsy: a manual of fundamental autopsy practice () 7. Diagnostic Pathology: Hospital Autopsy (Part III) Michiel van Mierevelt (1566–1641) and Pieter van Mierevelt (1596–1623), The Anatomy Lesson of Dr. Willem van der Meer (1617), oil on canvas, 146.5 x 202 cm, Museum Prinsenhof Delft, Delft, The Netherlands. Wikimedia Commons.