patoloji-ders-notlari

Title

Serdar Balcı

Pulmonary Infections

Serdar BALCI, MD

Innate defenses in lung

Entrapment in the mucous blanket

Removal by means of the mucociliary elevator

Phagocytosis by alveolar macrophages

Phagocytosis and killing by neutrophils recruited by macrophage factors

Serum complement may enter the alveoli and be activated by the alternative pathway to provide the opsonin C3b, which enhances phagocytosis

Draining lymph nodes initiate immune responses

Robbins Basic Pathology

Adaptive immunity

• Secreted IgA
  • Block attachment of the microorganism to epithelium in the upper respiratory tract
• IgM, IgG
  • In the lower respiratory tract, in the alveolar lining fluid
  • Activate complement more efficiently by the classic pathway, C3b
  • IgG is opsonic
• Accumulation of immune T cells

Robbins Basic Pathology

Predisposing factors for infection

• Mutations in MyD88
  • Adaptor protein downstream of many Toll-like receptors
    • Microbial sensors in innate immunity
  • Extremely susceptible to severe necrotizing pneumococcal infections
• Defects in TH1 cell–mediated immunity
  • Increased infections with intracellular microbes
  • Atypical mycobacteria
• Cigarette smoke
  • Compromises mucociliary clearance
  • Pulmonary macrophage activity
• Alcohol
  • Impairs cough and epiglottic reflexes
    • Increasing the risk of aspiration
  • Interferes with neutrophil mobilization and chemotaxis

Pneumonia

Any infection in the lung

Acute, fulminant clinical disease

Chronic disease with a more protracted course

Inflammation types in Pneumonia

• Fibrinopurulent alveolar exudate
  • Acute bacterial pneumonias
• Mononuclear interstitial infiltrates
  • In viral and other atypical pneumonias
• Granulomas and cavitation
  • Chronic pneumonias

Acute bacterial pneumoniasBronchopneumonia

A patchy distribution of inflammation

Involves more than one lobe

Initial infection of the bronchi and bronchioles

Extension into the adjacent alveoli

Robbins Basic Pathology

Bronchopneumonia

Patchy consolidation around small bronchi and bronchioles

Autopsy Pathology: A Manual and Atlas

necrotizing bronchopneumonia confluent gray areas

Autopsy Pathology: A Manual and Atlas

Lobar pneumonia

Contiguous air spaces of part or all of a lobe

Homogeneously filled with an exudate

Visualized on radiographs as a lobar or segmental consolidation

Streptococcus pneumoniae 90%

Robbins Basic Pathology

Gray hepatization stage

Gray-brown, dry, and firm

Right middle and lower lobes in this case

Autopsy Pathology: A Manual and Atlas

Pneumonia

• Anatomic distinction between lobar pneumonia and bronchopneumonia can often become blurry
  • Many organisms cause infections either patterns
  • Confluent bronchopneumonia can be hard to distinguish radiologically from lobar pneumonia
• Best to classify pneumonias either by the specific etiologic or clinical setting

Robbins Basic Pathology

Community-Acquired Acute Pneumonias

Bacterial

Infection follows a viral upper respiratory tract infection

S. pneumoniae most common cause

Streptococcus pneumoniae

• Underlying chronic diseases
  • CHF, COPD, diabetes
• Congenital or acquired immunoglobulin defects
  • AIDS
• Decreased or absent splenic function
  • Sickle cell disease, splenectomy
  • Spleen contains the largest collection of phagocytes, major organ responsible for removing pneumococci from the blood
  • Spleen important organ for production of antibodies against polysaccharides
    • Encapsulated bacteria.
• Lobar or bronchopneumonia
• Bronchopneumonia at the extremes of age
• Aspiration of pharyngeal flora
  • The lower lobes or the right middle lobe is most frequently involved
• Before antibiotics
  • Involved entire lobes
  • Four stages
    • Congestion
    • Red hepatization
    • Gray hepatization
    • Resolution

Congestion

Heavy, red, and boggy

Vascular congestion

Proteinaceous fluid, scattered neutrophils, and many bacteria in the alveoli

Within a few days red hepatization

Liver-like consistency

The alveolar spaces are packed with neutrophils, red cells, and fibrin

Lobar pneumonia in the stage of red hepatization, the entire right lower lobe is inflamed, hyperemic, and consolidated

Autopsy Pathology: A Manual and Atlas

Robbins Basic Pathology

Gray hepatization

Lung is dry, gray, and firm

Red cells are lysed, while the fibrinosuppurative exudate persists within the alveoli

Robbins Basic Pathology

Gross view of lobar pneumonia with gray hepatization

The lower lobe is uniformly consolidated

Robbins Basic Pathology

• Resolution
  • Uncomplicated cases
  • Exudates enzymatically digested
  • Granular, semifluid debris
  • Resorbed, ingested by macrophages
  • Organized by fibroblasts growing into it

Robbins Basic Pathology

• Pleural reaction

  • Fibrinous or fibrinopurulent pleuritis

• Resolve or undergo organization

• Fibrous thickening or permanent adhesions

• Bronchopneumonic pattern

  • Bilateral and basal
  • Well-developed lesions up to 3 or 4 cm
  • Slightly elevated
  • Gray-red to yellow
  • Lobar consolidation
  • Pleural involvement is less common
  • Focal suppurative exudate that fills the bronchi, bronchioles, and adjacent alveolar spaces

S. pneumoniae complications

• Serotype 3 pneumococci
• Tissue destruction and necrosis
  • Abscess
• Suppurative material accumulate in the pleural cavity
  • Empyema
• Organization of the intra-alveolar exudate
  • Fibrosis
• Bacteremic dissemination
  • Meningitis, arthritis, infective endocarditis

Robbins Basic Pathology

Community-Acquired Atypical Pneumonias

Acute febrile respiratory disease

Patchy inflammatory changes in the lungs

Confined to the alveolar septa and pulmonary interstitium

Mycoplasma pneumoniae most common

• Attachment of the organisms to the respiratory epithelium
• Necrosis of the cells
• Inflammatory response
• Extends to alveoli → interstitial inflammation
• Outpouring of fluid into alveolar spaces
• Damage to and denudation of the respiratory epithelium
  • Inhibits mucociliary clearance
  • Predisposes to secondary bacterial infections

Patchy

Whole lobes bilaterally or unilaterally

Red-blue, congested

Inflammatory reaction is largely confined within the walls of the alveoli

Septa are widened and edematous

Mononuclear inflammatory infiltrate of lymphocytes, histiocytes, and, occasionally, plasma cells

Alveolar spaces in atypical pneumonias are remarkably free of cellular exudate

• In severe cases, full-blown diffuse alveolar damage with hyaline membranes may develop
• In less severe, uncomplicated cases
  • Subsidence of the disease
  • Reconstitution of the native architecture
• Superimposed bacterial infection
  • Results in a mixed histologic picture

Viral pneumonia

Thickened alveolar walls infiltrated with lymphocytes and some plasma cells, spilling over into alveolar spaces.

Focal alveolar edema

Early fibrosis at upper right

Robbins Basic Pathology

Robbins Basic Pathology

Hospital-Acquired Pneumonias

Acquired in the course of a hospital stay

Severe underlying disease

Immunosuppressed

Prolonged antibiotic regimens

Mechanical ventilation

Robbins Basic Pathology

Aspiration Pneumonia

• Debilitated patients
• Unconscious, stroke
• Repeated vomiting
• Chemical
  • Extremely irritating effects of the gastric acid
• Bacterial
  • Aerobes more commonly than anaerobes

Robbins Basic Pathology

Lung abscess

• Localized area of suppurative necrosis
• Resulting in the formation of one or more large cavities
• Anaerobic bacteria are present in almost all lung abscesses
  • Commensals normally found in the oral cavity
  • Prevotella, Fusobacterium, Bacteroides, Peptostreptococcus, microaerophilic streptococci
• Aspiration of infective material
  • From carious teeth
  • Infected sinuses or tonsils
  • Oral surgery, anesthesia, coma, alcoholic intoxication, debilitated patients with depressed cough reflexes
• Aspiration of gastric contents
  • Accompanied by infectious organisms from the oropharynx
• Complication of necrotizing bacterial pneumonias
  • S. aureus, Streptococcus pyogenes, K. pneumoniae, Pseudomonas spp., and, rarely, type 3 pneumococci
  • Mycotic infections and bronchiectasis
• Bronchial obstruction
  • Bronchogenic carcinoma
  • Impaired drainage, distal atelectasis, aspiration of blood and tumor fragments
• Septic embolism
  • Septic thrombophlebitis, infective endocarditis of the right side of the heart
• Hematogenous spread of bacteria
  • Disseminated pyogenic infection
  • Staphylococcal bacteremia
  • Multiple lung abscesses
• From a few millimeters to large cavities 5 to 6 cm across
• Localization and number depend on their mode of development
  • Aspiration of infective material
    • Common on the right side (more vertical airways)
    • Single
• Pneumonia or bronchiectasis
  • Multiple, basal, and diffusely scattered
• Septic emboli, hematogenous seeding
  • Multiple
  • Any region

Necrotizing bronchopneumoni

Multiple abscess cavities

S. aureus

Autopsy Pathology: A Manual and Atlas

Lung abscess complications

• Suppuration enlarges → Ruptures into airways
  • Exudate may be partially drained
    • Air-fluid level on radiographic examination
• Rupture into the pleural cavity
  • Bronchopleural fistulas
  • Pneumothorax, empyema
• Embolization of septic material to the brain
  • Meningitis, brain abscess
• Amyloidosis

Lung abscess

• Histologically;
• Suppurative focus
• Variable amounts of fibrous scarring
• Mononuclear infiltration
  • Lymphocytes, plasma cells, macrophages

Robbins Basic Pathology

Chronic pneumonia

• Localized lesion in an immunocompetent person
• With or without regional lymph node involvement
• Granulomatous inflammation
  • Bacteria (M. tuberculosis)
  • Fungi
• Immunocompromised patients
• Debilitating illness
• Immunosuppressive regimens
• HIV
• Systemic dissemination of the causative organism

Histoplasmosis, Coccidioidomycosis, Blastomycosis

• Dimorphic fungi
  • isolated pulmonary involvement
  • disseminated disease in immunocompromised
• T cell–mediated immune responses

Endemic in the Ohio and central Mississippi River valleys

Warm, moist soil, growth of the mycelial form, which produces infectious spores

Robbins Basic Pathology

Disseminated coccidioidomycosis causing miliary-like lesions, diffuse alveolar damage, and cyst formation

Autopsy Pathology: A Manual and Atlas

C. Immitis

Thick-walled, nonbudding spherules, 20 to 60 µm in diameter, often filled with small endospores

Endemic in the southwestern and far western regions of the United States

Robbins Basic Pathology

B. dermatitidis : round to oval and larger than Histoplasma (5 to 25 µm in diameter); reproduce by characteristic broad-based budding

Robbins Basic Pathology

Robbins Basic Pathology

Robbins Basic Pathology

Pneumonia in the Immunocompromised Host

• Opportunistic pathogens
• Bacterial
  • P. aeruginosa , Mycobacterium spp., L. pneumophila, Listeria monocytogenes
• Viral
  • Cytomegalovirus and Herpesvirus
• Fungal
  • P. jiroveci, Candida spp., Aspergillus spp., Cryptococcus neoformans

CMV

Herpesvirus

Gigantism of both the entire cell and its nucleus

Nucleus is an enlarged inclusion surrounded by a clear halo (“owl’s eye”)

Organizing diffuse alveolar damage in cytomegalovirus pneumonia

Autopsy Pathology: A Manual and Atlas

Patchy necrosis related to Herpes simplex virus pneumonia

Autopsy Pathology: A Manual and Atlas

Robbins Basic Pathology

P. jiroveci

Everyone exposed to Pneumocystis during the first few years of life

Most the infection remains latent

Reactivation in immunocompromised

Necrotizing and cavitating infection with Pneumocystis carinii in a child with congenital AIDS

Autopsy Pathology: A Manual and Atlas

“cotton candy” exudate

septa are thickened by edema and a minimal mononuclear infiltrate

Robbins Basic Pathology

__ intracystic bodies but without budding in alveolar exudate__

Robbins Basic Pathology

Candidiasis

• Candida albicans
• Normal inhabitant of the oral cavity, gastrointestinal tract, and vagina
• Yeastlike forms (blastoconidia), pseudohyphae, and true hyphae
• Candida pneumonia
  • Bilateral nodular infiltrates

Robbins Basic Pathology

Aspergillus

• Invasive aspergillosis
  • Immunosuppressed
  • Localizes to the lungs
  • Necrotizing pneumonia
  • Systemic dissemination, to the brain, is an often fatal complication

Invasive aspergillosis causing necrotizing pneumonia and diffuse alveolar damage

Autopsy Pathology: A Manual and Atlas

Robbins Basic Pathology

Robbins Basic Pathology

• Allergic bronchopulmonary aspergillosis
  • Type I hypersensitivity against the fungus growing in the bronchi
  • IgE antibodies against Aspergillus
  • Peripheral eosinophilia
• Aspergilloma (fungus ball)
  • Colonization of preexisting pulmonary cavities
  • Ectatic bronchi, Lung cysts, Posttuberculosis cavitary lesions

Mucormycosis

Rhizopus and Mucor

Nondistinctive, suppurative, sometimes granulomatous reaction with a predilection for invading blood vessel walls, causing vascular necrosis and infarction

Localized necrotizing infection related to zygomycosis (mucormycosis)

Autopsy Pathology: A Manual and Atlas

Cryptococcosis

• C. neoformans
• 5-10 µm yeast, has a thick, gelatinous capsule and reproduces by budding
• Pseudohyphal or true hyphal forms are not seen
• Routine H&E stains, the capsule is not directly visible,
  • Clear “halo” can be seen surrounding the individual fungi representing the area occupied by the capsule
• India ink or periodic acid–Schiff
• Capsular polysaccharide antigen cryptococcal latex agglutination assay

Acquired by inhalation from the soil or from bird droppings

Localizes in the lungs and then disseminates to other sites, particularly the meninges

Robbins Basic Pathology

Pulmonary Disease in HIV

• Bacterial pneumonias
  • More common, more severe, and more often associated with bacteremia than in those without HIV infection
  • S. pneumoniae, S. aureus, H. influenzae, and gram-negative rods

Neoplastic lesions occur with increased frequency and must be excluded

Kaposi sarcoma

Non-Hodgkin lymphoma

Primary lung cancer

• Bacterial and tubercular infections are more likely at higher CD4+ counts
  • > 200 cells/mm 3
• Pneumocystis pneumonia
  • CD4+ counts <200 cells/mm 3
• CMV and M. avium complex infections are uncommon until the very late stages of immunosuppression
  • CD4+ counts < 50 cells/mm 3
• Pulmonary disease in HIV-infected persons
  • May result from more than one cause
  • Common pathogens may be responsible for disease with atypical manifestations