Pathology Lung Infection 2 (2025) - Pneumonia

LUNG INFECTIONS 2 Department of Anatomical Pathology 11 February 2025 Dr N Buthelezi OUTLINE Pulmonary host defences Classification of pneumonia Aetiological Anatomical Clinical Pneumonia - special types Pneumonia in immunocompromise PULMONARY HOST DEFENSE...

LUNG INFECTIONS 2 Department of Anatomical Pathology 11 February 2025 Dr N Buthelezi OUTLINE Pulmonary host defences Classification of pneumonia Aetiological Anatomical Clinical Pneumonia - special types Pneumonia in immunocompromise PULMONARY HOST DEFENSE MECHANISMS Impairment of any of these mechanisms can lead to pneumonia Compromise In Pulmonary Host Defense Mechanisms Loss of suppression of cough reflex Coma, anaesthesia, neuromuscular disorders, drugs, post- surgery, chest pain Injury to mucociliary apparatus Impairment of ciliary function, destruction of ciliated epithelium due to cigarette smoke, inhalation of hot or corrosive gases, viral diseases or immotile cilia syndromes Interference with phagocytic action of alveolar macrophages Alcohol, tobacco smoke, anoxia, oxygen intoxication Pulmonary congestion and oedema Accumulation of secretions Cystic Fibrosis and bronchial obstruction PNEUMONIA Definition: infection of the lung parenchyma Due to infection affecting distal airways and alveoli, with the formation of an inflammatory exudate. Caused by a wide variety of infective pathogens. Pneumonia results when the lung defense mechanisms are impaired or When resistance of the host is lowered. TYPE AETIOLOGICAL AGENTS COMMUNITY-ACQUIRED ACUTE PNEUMONIA Streptococcus pneumonia, Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, Legionella pneumophila, Enterobacteriaceae (Klebsiellapneumoniae) and Pseudomonas spp. COMMUNITY-ACQUIRED ATYPICAL PNEUMONIA Bacteria Mycoplasma pneumonia, Chlamydia spp. (C. pneumoniae, C. psittaci, C. trachomatis) Coxiellaburnetii(Q fever) Viruses Respiratory syncytial virus, parainfluenza virus and human metapneumovirus (children); influenza A and B (adults); adenovirus (military recruits); SARS virus HOSPITAL-ACQUIRED PNEUMONIA Gram-negative rods, Enterobacteriaceae (Klebsiellaspp., Serratiamarcescens, Escherichia coli) and Pseudomonas spp. Staphylococcus aureus (usually methicillin-resistant) HEALTH CARE-ASSOCIATED PNEUMONIA Staphylococcus aureus, methicillin-sensitive Staphylococcus aureus, methicillin-resistant Pseudomonas aeruginosa Streptococcus pneumoniae ASPIRATION PNEUMONIA Anaerobic oral flora (Bacteroides, Prevotella, Fusobacterium, Peptostreptococcus), admixed with aerobic bacteria (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa) CHRONIC PNEUMONIA Nocardia, Actinomyces Granulomatous: Mycobacterium tuberculosis and atypical mycobacteria, Histoplasmacapsulatum, Coccidioidesimmitis, Blastomycesdermatitidis NECROTIZING PNEUMONIA AND LUNG ABSCESS Anaerobic bacteria (extremely common), with or without mixed aerobic infection Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pyogenes, and type 3 pneumococcus (uncommon) PNEUMONIA IN THE IMMUNOCOMPROMISED HOST Cytomegalovirus, Pneumocystis jiroveci Mycobacterium avium-intracellulare Invasive aspergillosis, Invasive candidiasis “Usual” bacterial, viral, and fungal organisms CLASSIFICATION OF PNEUMONIA ANATOMICAL CLASSIFICATION OF PNEUMONIA Lobar pneumonia Bronchopneumonia Whole lobe of the lung is affected There is patchy consolidation involving the lung OVERLAP BRONCHOPNEUMONIA PREDISPOSING CONDITIONS Extremes of age: infants and elderly Debilitating diseases: cardiac failure, chronic renal failure, CVA Pre-existing lung conditions: acute bronchitis, chronic obstructive airway disease , cystic fibrosis. Failure to clear respiratory secretions: post-operative. Manifestation 2º to viral infection: influenza, measles. AETIOLOGICAL AGENTS Streptococcus pneumoniae Klebsiella pneumoniae Staphylococcus aureus Streptococcus pyogenes Haemophilus influenzae Pseudomonas aeruginosa Legionella pneumophila CLINICAL FEATURES Fever Reduced consciousness Crackles (crepitations) on auscultation Septicaemia PATHOGENESIS Organisms colonise the bronchioles to cause bronchiolitis. Inflammation spreads through the wall of a bronchiole into surrounding alveoli. There may be significant damage to bronchiolar walls. PATHOLOGY GROSS MORPHOLOGY Patchy consolidation Basal and bilateral lesions Initially focal, involving one or more lobes Findings: Elevated, dry, granular, grey-red to yellow lesions Poorly delimited at their margins MICROSCOPIC FEATURES Neutrophil-rich exudate that fills the bronchi, bronchioles, and adjacent alveolar spaces. Ciliated epithelium of bronchioles is damaged. Capillaries are congested Intervening lung tissue is not affected unless areas of bronchopneumonia become confluent. If bronchioles are blocked, lung tissue can develop compensatory emphysema. LOBAR PNEUMONIA Consolidation of entire lobe/large part of a lobe Inflammatory cells in alveoli and airways PREDISPOSING CONDITIONS Adults ages 20-50 Male predominance Elderly, diabetics, alcoholics AETIOLOGICAL AGENTS Streptococcus pneumoniae infection common Klebsiella pnumoniae CLINICAL FEATURES -Acute onset -Fever, rigors -Dry cough -Rusty sputum -Pleuritic chest pain PATHOGENESIS Organism inhaled into bronchial tree and reaches alveoli. Bacteria cause an inflammatory exudate which is initially watery. Later, there is exudation of fibrin and neutrophils in the alveoli. Alveoli filled with exudate = consolidation. Exudate flows directly into the next alveolus via pores of Kohn, carrying bacteria with it. Infection spread is through lumen rather than through walls. This is important in that the damage to bronchioles is much less than in bronchopneumonia. Four stages of lobar pneumonia 1. Congestion (1-2 days) Capillary congestion, alveolar oedema, numerous bacteria and few neutrophils Lung is heavy, boggy and red. 2. Red hepatization ( Also called early consolidation) (2-4 days). Macroscopic Red, firm and airless. Mass is increased (up to 1kg). Surface of lung shows fibrinous pleurisy/pleuritis. Sharp demarcation between normal and abnormal lung Lung has liver-like consistency. Lung tissue friable and sinks in water. Microscopic Congestion, neutrophils, fibrin, bacteria, oedema. Four stages of lobar pneumonia 3.Grey hepatization (late consolidation)(4-8 days). Disintegration of red blood cells Persistence of fibrinosuppurative exudate Microscopic Neutrophils still present Fibrin is denser Bacteria hard to find Four stages of lobar pneumonia 4. Resolution (starts at around 8 days. Takes 1-3 weeks.) Lung goes back to normal. Macroscopic Lung becomes patchy grey and red. Pleurisy begins to resolve -> Fibrous thickening or adhesions Microscopic Macrophages remove degenerate cells and exudate. Neutrophil enzymes help to liquefy the exudate. Fluid in the alveolar spaces is drained away by lymphatics and capillaries. Lung gradually undergoes re-aeration and returns to normal. COMPLICATIONS OF PNEUMONIA Healing with fibrosis leading to bronchiectasis Lung Abscess: due to tissue destruction and necrosis (particularly common in pneumococcal or Klebsiella infections) Empyema: pus collection in pleural space following spread of infection to pleura (pleuritis/pleurisy) – more common in lobar pneumonia. Spread of inflammation Local Eg. pericarditis (contiguous spread) Via bloodstream Septicaemia Heart valves (endocarditis) Pericardium Brain (meningitis) Kidneys Spleen Joints (suppurative arthritis) Complications of pneumonia Organization with fibrosis and bronchiectasis Lung abscess  Community-acquired Atypical Pneumonias Acute febrile respiratory disease characterized by patchy inflammatory changes in the lungs, largely confined to the alveolar septa and pulmonary interstitium. The term "atypical" denotes The moderate amounts of sputum and absence of physical findings of consolidation, Only moderate elevation of white cell count, and lack of alveolar exudates. Community-acquired Atypical Pneumonias Mycoplasma pneumoniae Particularly common among children and young adults. Occur sporadically or as local epidemics in closed communities (schools, military camps, prisons). Chlamydia pneumoniae Milder pneumonia Relatively common in asthmatics Legionella pneumophila Causes severe pneumonia Legionnaires’ disease Viral pneumonia Influenza Human metapneumovirus Coronavirus Influenza Single-stranded RNA virus, bound by a nucleoprotein that determines the virus type (A, B, or C). The spherical surface of the virus contains the viral hemagglutinin and neuraminidase, which determine the subtype (e.g., H1N1, H3N2, etc.). The type A viruses infect humans, pigs, horses, and birds and are the major cause of pandemic and epidemic influenza infections. Influenza Commercially available influenza vaccines provide reasonable protection against the disease, especially in vulnerable infants and elderly individuals. A particular subtype of avian influenza ("bird flu," H5N1) has caused massive outbreaks in domesticated poultry in parts of Southeast Asia. This strain is particularly dangerous, since it has the potential to "jump" to humans and thereby cause an unprecedented, worldwide influenza pandemic. Human metapneumovirus Paramyxovirus Common in young, elderly, immunocompromised Can develop severe infection Human coronavirus Enveloped, positive-sense RNA viruses Infect humans and other vertebrate species Cold-like URTI to severe pneumonia Bind ACE2 protein on surface of alveolar epithelium Host immune response and locally released cytokines often produce Acute Respiratory Distress Syndrome (ARDS)  SEVERE ACUTE RESPIRATORY SYNDROME (SARS) Caused by coronavirus (SARS-CoV). Able to infect the lower respiratory tract and induce viraemia. Spread is through person-to-person, mainly through infected secretions Symptoms include fever, myalgias, headache, chills, and occasionally diarrhoea. Respiratory symptoms include dry cough and dyspnea. The lungs of patients dying of SARS usually demonstrate diffuse alveolar damage. NOSOCOMIAL INFECTIONS Also known as hospital-acquired, pneumonias are defined as pulmonary infections acquired in the course of a hospital stay. Common in hospitalized persons with severe underlying disease, immunosuppression, or prolonged antibiotic therapy. Those on mechanical ventilation represent a particularly high-risk group, and infections acquired in this setting are given the distinctive designation ventilator-associated pneumonia.  ASPIRATION PNEUMONIA Aspiration pneumonia occurs in debilitated patients or those who aspirate gastric contents either while unconscious (e.g. after a stroke) or during repeated vomiting. These individuals have abnormal gag and swallowing reflexes that facilitate aspiration. The resultant pneumonia is partly chemical, resulting from the irritating effects of gastric acid, and partly bacterial. Although it is commonly assumed that anaerobic bacteria predominate, recent studies implicate aerobes more commonly than anaerobes. This type of pneumonia is often necrotizing, pursues a fulminant clinical course, and is a frequent cause of death in persons predisposed to aspiration. Abscess formation is a common complication. LUNG ABSCESS A localized area of suppurative necrosis within the pulmonary parenchyma, resulting in the formation of one or more large cavities. More common on right side following aspiration More common basally and bilaterally in pneumonia The causative organism may be introduced into the lung by any of the following mechanism Aspiration of infective material (the most frequent cause). acute alcoholism, coma, anesthesia, sinusitis, gingivodental sepsis, and debilitation. Aspiration first causes pneumonia which progresses to tissue necrosis and formation of lung abscess. Antecedent primary lung infection. Usually associated with S. aureus, K. pneumoniae, and type 3 pneumococcus. Post-transplant or otherwise immunosuppressed individuals are at special risk. Septic embolism. Infected emboli from thrombophlebitis or due to vegetations of infective bacterial endocarditis on the right side of the heart. Neoplasia. Secondary infection is particularly common in the bronchopulmonary segment obstructed by a primary or secondary malignancy (postobstructive pneumonia). Miscellaneous. Direct traumatic penetrations of the lungs; spread of infections from a neighboring organ, such as suppuration in the oesophagus, spine, subphrenic space or pleural cavity; and hematogenous seeding of the lung by pyogenic organisms. LUNG ABSCESS Suppurative destruction of the lung parenchyma within the central area of cavitation. CHRONIC PNEUMONIA Histoplasmosis capsulatum Warm, moist soil contaminated by droppings from bats and birds containing fungal spores More common in immunocompromised Cause granulomatous inflammation in lung Yeast forms: round to oval, 2 to 4 μm in diameter. Coccidioides immitis Endemic in the Southwest and Far West of the United States, particularly in California's San Joaquin Valley, where it is known as "valley fever.“ Yeast forms: thick-walled, non-budding spherules, 20 to 60 μm in diameter, often filled with small endospores. Blastomyces dermatitidis Three clinical forms: Pulmonary blastomycosis Disseminated blastomycosis Rare primary cutaneous form (from direct inoculation of organisms into the skin). Cause suppurative granulomatous inflammation Yeast forms: round to oval and larger than Histoplasma (5-15 μm in diameter). Thick double- contoured wall. Broad-based budding.  Pneumonia in the Immunocompromised Host Immunocompromised: By disease – eg. HIV By immunosuppressive therapy – eg. for organ transplant By chemotherapy or irradiation for cancers Usual pathogens plus opportunistic infections Can be polymicrobial Pneumonia in the Immunocompromised Host Common bacterial Less common pathogens bacterial pathogens  S. pneumonia M. catarrhalis  H. influenza N. asteroides  S. aureus M. avium complex  M. tuberculosis M. kansasii & spp. Fungi: -Pneumocystis jirovecii - C. neoformans - H. capsulatum - C. immitis - Aspergillus spp. Protozoa: - T. gondii - Cryptosporidium - Strongyloides stercoralis Viruses - Cytomegalovirus Cytomegalovirus Herpesvirus Cause interstitial pneumonitis with necrosis Can progress to ARDS Giant cells with giant nuclei Nuclear inclusion surrounded by clear halo (“owls eye”) CMV in the lung Pneumocystis jiroveci Previously known as Pneumocystis Carinii Pneumonia (PCP) Now classified as a fungus Condition : Pneumocystis Jirovecii Pneumonia (PJP) Often initial presentation of HIV and can affect 60-80% of HIV patients Variety of changes on CXR Widespread bilateral consolidation Alveoli filled with bubbly pink exudates Round or crescent shaped organisms identified on methenamine silver or toludine blue stain Pathology Interstitial lung disease Lymphoplasmacytic interstitial infiltrates (LIP) Nodular and granulomatous PJP Cavitary PJP Microscopically, Intra-alveolar foamy, pink- staining exudate ("cotton candy" exudate). Silver stains show cup-shaped cyst walls (5-8 μm in diameter) in the alveolar exudates resembling crushed ping pong balls  Aspergillus fumigatus Mould Hyphae Fruiting bodies Pathology Allergic bronchopulmonary aspergillosis Aspergilloma (fungal ball) Invasive and septicaemic Septicaemic aspergillosis Chronic necrotising aspergillus pneumonia Mucormycosis Caused by Rhizopus and Mucor fungi of the Zygomycetes class. Hyphae Both Zygomycetes and Aspergillus Cause a nondistinctive, suppurative, sometimes granulomatous reaction Have a predilection for invading blood vessel walls, causing vascular necrosis and infarction. Common in diabetic patients. Thank you Kumar, Abbas, Aster. Robbins & Contran Pathologic Basis of Disease 10th Ed. Elsevier.