Pulmonary Infectious Diseases PDF

Pulmonary Infectious Diseases Eugen Petcu, MD, PhD Associate Professor Department of Biomedical Sciences [email protected] Office of Academic Affairs Session Objectives 1. This presentation will offer you the opportunity to become familiar with the mechanisms leading to (community acquired) bacteri...

Pulmonary Infectious Diseases Eugen Petcu, MD, PhD Associate Professor Department of Biomedical Sciences [email protected] Office of Academic Affairs Session Objectives 1. This presentation will offer you the opportunity to become familiar with the mechanisms leading to (community acquired) bacterial pneumonia and (community acquired) interstitial pneumonia and their morphology. 2. You will be able to define health care (nosocomial pneumonia), aspiration pneumonia including lung abscess. 3. In addition, you will be able to discuss and explain the morphology of chronic pneumonia caused by Mycobacterium tuberculosis, Histoplasma capsulatum, Blastomyces dermatitides and Coccidioides immitis. 3. Also, you will be able to describe morphology of the most common forms of pneumonia caused by opportunistic agents in HIV patients. Please note that unless mentioned otherwise, all the images and information included in this presentation are from Robbins and Cotran, Pathologic Basis of Disease, 10th edition  Pneumonia Pneumonia is an infection of the lung parenchyma : a. Lowered (decreased) systemic resistance of the host : chronic diseases, immunologic deficiencies, leukopenia treatment with immunosuppressive agents b. Impaired local defense mechanisms: Loss or suppression of the cough reflex: altered sensorium (e.g., coma), anesthesia, neuromuscular disorders, leading to aspiration of gastric contents. Dysfunction of the mucociliary apparatus: cigarette smoke, inhalation of hot or corrosive gases, viral diseases, or genetic defects of ciliary function (e.g., immotile cilia syndrome). Accumulation of secretions : cystic fibrosis and bronchial obstruction. Interference with the phagocytic and bactericidal activities of alveolar macrophages by alcohol, tobacco smoke, anoxia, or oxygen intoxication. Pulmonary congestion and edema. Classification Bacterial Pneumonia The alveoli show an inflammatory exudate, causing consolidation (“solidification”) of the pulmonary tissue. Predisposing conditions: -extremes of age, chronic diseases (congestive heart failure, COPD, and diabetes), -congenital or acquired immune deficiencies -decreased or absent splenic function: risk for infection with encapsulated bacteria such as pneumococcus. The clinical picture is markedly modified by the Clinical Features administration of effective antibiotics. Appropriately -abrupt onset of high fever, shaking chills, treated patients may become afebrile with few and cough producing mucopurulent sputum clinical signs 48 to 72 hours after the initiation of and occasionally hemoptysis. antibiotics. The identification of the organism and the -If there is associated pleuritis the patient determination of its antibiotic sensitivity are the will develop pleuritic pain (on inspiration) keystones of therapy and pleural friction rub. Bacterial Pneumonia Morphology Bronchopneumonia: patchy consolidation; extension of previous bronchitis or bronchiolitis; seen in infancy and old age The patchy involvement may become confluent, producing lobar consolidation. Lobar Pneumonia: consolidation of a large portion of a lobe or entire lobe or the whole lung. The same organisms may produce either pattern depending on patient susceptibility. First Aid Step I USMLE, 2022 Natural history of lobar pneumonia Red Hepatization Congestion of lung The congested septal capillaries and numerous intra-alveolar neutrophils. Fibrin nets have not yet formed. Grey Hepatization The lower lobe is uniformly consolidated Exudate full of neutrophils and fibrin strands deposition Bronchopneumonia Morphology It is characterized by patchy areas of pulmonary consolidation, which are firmer than the surrounding lung. The inflammatory exudate may be confined to one lobe or may be multi-lobar. Well-developed lesions: slightly elevated, dry, granular, gray-red to yellow, and poorly delimited at their margins Cut surface of lung shows areas of tan- yellow consolidation. Histologically, the reaction usually elicits a neutrophil-rich exudate that fills the bronchi, Webpath bronchioles, and adjacent alveolar spaces Bronchopneumonia Complications: -Tissue destruction and necrosis causing abscess formation -Empyema which represents spread of inflammation and destruction to pleura -Organization of exudate to solid tissue -Bacteremia with dissemination to heart valves, pericardium, brain, kidneys, spleen, joints Interstitial (atypical) Pneumonia Atypical = moderate amount of sputum, no physical findings of consolidation, lack of alveolar exudate Viral Pneumonia Viruses have epithelial respiratory cells tropism. Viral replication and gene expression leads to cytopathic changes, inducing cell death and secondary inflammation. The resulting damage and impairment of local pulmonary defenses, such as mucociliary clearance, may predispose to bacterial superinfections, which are often more serious than the viral infection itself. Factors that favor extension of the infection to the lung : Extremes of age, Malnutrition, Alcoholism Viral Pneumonia: Morphology All viral infections produce similar morphologic changes Upper respiratory infections : - mucosal hyperemia and swelling -overproduction of mucus secretions The swollen mucosa and viscous exudate may plug the nasal channels, sinuses, or the Eustachian tubes, leading to secondary suppurative bacterial infection. Histology -Interstitial inflammatory reaction in the Children: virus-induced tonsillitis causing hyperplasia of walls of the alveoli. the lymphoid tissue within the Waldeyer ring -The alveolar septa are thick: mononuclear inflammatory infiltrate. Macroscopic lung involvement : -patchy or may involve whole lobes bilaterally or - If associated with ARDS, pink hyaline unilaterally membranes line the alveolar walls. -the affected areas are red-blue and congested Pleuritis or pleural effusions are infrequent Adenovirus Necrotizing pneumonia with cellular debris in alveolar spaces Cytomegalovirus Viral inclusions: dark nucleus in the Cytomegaly with basophilic center of this image cytoplasmic inclusions and nuclear inclusions Viral Pneumonia: Influenza type A Represents a major cause of pandemic and epidemic influenza. : humans, pigs, horses, and birds Influenza type A: Influenza A has a viral envelope containing 2 proteins: antigenic drift: mutations of the hemagglutinin and neuraminidase. hemagglutinin and neuraminidase which allow virus to escape host Hemagglutinin: viral attachment antibodies. Neuraminidase: promote release of newly formed antigenic shift: hemagglutinin and virions neuraminidase are replaced through recombination of RNA segments with other viruses or dif strains of influenza A Cellular destruction release chemokines and cytokines which will exacerbate inflammation. Influenza type B and C: No antigenic drift and shift, mostly peds Influenza type A: Morphology Mucosa: hyperaemia and swelling Submucosa: lymphocytes, monocytes, and plasma Overproduction of mucus, bacterial superinfection and ARDS may occur Macroscopic: lungs are congested, Microscopic: Alveolar walls are heavier and redder than normal and thickened, and there is deposition of uniformly firm throughout. hyaline membranes Interstitial (atypical) Pneumonia: Mycoplasma pneumoniae It is common among children and young adults It may occur sporadically or as local epidemics in closed communities Clinical Fever without chills Mp has adherence proteins; Dry cough: inhibition of ciliary movement It secretes hydrogen peroxide damaging the Diffuse crackles respiratory epithelium Complications Activation of cytokines and other inflammatory Hemolysis factors ITP IgM and IgG antibodies act as autoantibodies that Acute hepatitis cross react with neural cells and RBC Arthritis Transverse myelitis GI symptoms Heart Disease Morphology Respiratory epithelial injury occurs after attachment of Mp to resp mucosa Lesions may be patchy or may involve whole lobes bilaterally or unilaterally Mp secretes peroxide: ulceration of mucosa. Histology Inflammatory reaction, localized within walls of alveoli; The alveolar septa are widened by an infiltrate: lymphocytes, histiocytes, and some plasma cells (short arrows). Alveoli may show intra-alveolar proteinaceous material  Health-care (Nosocomial) Pneumonia : pulmonary infections acquired during a hospital stay: -in patients with severe underlying disease, immunosuppression, prolonged antibiotic therapy, invasive access devices such as intravascular catheters. -patients on mechanical ventilation are at particularly high risk. These patients have a higher mortality than those with community- acquired pneumonia. Methicillin-resistant S. aureus: Bronchopneumonia Pseudomonas aeruginosa In patients with cystic fibrosis, emphysema and long-term hospitalizations Macro P. aeruginoas: Erythematous patch surrounded by a tan rim. Cavitation will develop and may Micro P aeruginosa: Blue areas: neutrophilic result in abscess formation debris surrounding large vessels. Aspiration Pneumonia It is partly chemical due to the irritating effects of gastric acid It is partly bacterial from inoculation of the the oral flora More than one organism is recovered on culture, aerobes being more common than anaerobes. Morphology: Necrotizing lung inflammation: frequent cause of death. In patients who survive we may see lung abscess development. Micro: Inflammatory infiltrate: PMNs, Eosinophils, Lymphocytes. Lung Abscess Aspiration of oropharyngeal content/Bronchial obstruction Aspiration of infective material: the most frequent cause: Bacteroides, Fusobacterium, and Peptococcus Antecedent primary lung infection: S. aureus, K. Clinical features –Cough and copious amounts pneumoniae, and pneumococcus. of foul-smelling purulent sputum, fever Chest pain, and weight loss are common. Neoplasia: Secondary infection is common in Clubbing of the fingers and toes may appear. bronchopulmonary segments obstructed by a primary or The diagnosis must be confirmed radiologically. secondary malignancy (postobstructive pneumonia). Abscess is in elderly: rule out an underlying carcinoma, which is present in 10% to 15% of Septic embolism: thrombophlebitis, infective bacterial cases. endocarditis on the right side of the heart Therapy -antibiotics Miscellaneous: Traumatic penetrations of the lungs; direct Complications : pleural effusion, hemorrhage, extension of suppurative infections from the esophagus, brain abscesses or meningitis from septic spine, subphrenic space, or pleural cavity emboli, and (rarely) secondary amyloidosis. Lung Abscess Morphology Two abscesses Aspiration: R side abscess as right main bronchus is vertical; single. After pneumonia or bronchiectasis: abscesses Histology: suppurative destruction of lung are usually multiple, basal, and diffusely tissue within central area of cavitation; chronic scattered abscesses have fibrosis.  Chronic Pneumonia It is most often a localized lesion in the immunocompetent patient, with or without regional lymph node involvement. The inflammatory reaction is granulomatous and is caused by bacteria (Mycobacterium tuberculosis ) or fungi. Mycobacteria tuberculosis -Granulomatous inflammation Fungal: Histoplasmosis Blastomycosis Coccidioidomycosis -Histo: Ohio and Mississippi Rivers and Caribbean -Blasto: Southeastern US -Coccidio: Southwest and West US and Mexico Chronic Pneumonia: Mycobacterium tuberculosis Primary TB: Granuloma and Acute pneumonia which later becomes chronic It occurs in previously unexposed, unsensitized person: approx. 1 cm grey-white inflammatory consolidation in lung, GHON FOCUS (central necrosis)-subpleural, often upper lobe nodule; The micro-organisms drain to nearby lymph nodes which also caseate; The lung lesion + lymph node involvement = GHON COMPLEX= GHON FOCUS plus lymphatic or hilar lymph node involvement Histology: elongated/epithelioid histiocytes, Most common location for Ghon complex: lower giant cells with a peripheral cuff of lobe or anterior segment of the upper lobe. lymphocytes and plasma cells. Identification: Sputum smear stained with carbolfuchsin –Ziehl- Neelson method Mycobacteria are acid-fast (retain stains when treated with acid and alcohol) because of waxy cell wall made of mycolic acid Gold standard for dx: culture Key elements of pathogenesis: -M. tuberculosis morphological changes can be explained as the outcome of a Th1 response. -CD4 lymphocytes aka Helper T cells: Th1 and Th2 lymphocytes Macrophages are primary cells infected and after 3 weeks, a Th1 response (produce IFN-gamma) against organisms occurs which activates macrophages to kill the mycobacteria; Acid fast bacili : Ziehl- However, at the same time a Th1 response also promotes Neels/Carbolfuchsin coloration granuloma formation and necrosis: hypersensitivity response leads to tissue destruction. Degenerated cells  Secondary (Reactivation) Pulmonary tuberculosis Represents M. Tuberculosis in an immunocompetent individual. It is also known as Post-primary Tuberculosis. Only 5% to 10% of patients with primary tuberculosis will develop secondary form. It begins at the apex of lung as a small focus (