Pulmonary Infections PDF

PULMONARY INFECTIONS Dr Tshepile Tlali Anatomical Pathology Registrar Wits University 14 May 2024 [email protected]  PULMONARY IMMUNITY In the United States, pulmonary infections responsible for approximately one- sixth of...

PULMONARY INFECTIONS Dr Tshepile Tlali Anatomical Pathology Registrar Wits University 14 May 2024 [email protected]  PULMONARY IMMUNITY In the United States, pulmonary infections responsible for approximately one- sixth of all deaths Risen during the COVID-19 pandemic. Pneumonia can be broadly defined as any infection in the lung. Normally, the lung remains sterile because of immune and nonimmune defense mechanisms present throughout the respiratory system from the nasopharynx to the alveolar air spaces Vulnerability of the lung to infection despite these defenses is not surprising because Many microbes are airborne and readily inhaled into the lungs Nasopharyngeal flora is regularly aspirated during sleep, even by healthy individuals Lung diseases often lower local immune defenses.  PULMONARY IMMUNITY Importance of immune defenses in preventing pulmonary infections emphasized by impact of inherited or acquired defects in innate immunity (including neutrophil and complement defects) or adaptive immunity (e.g., humoral immunodeficiency). All of which increase the incidence of bacterial pneumonia. Much more commonly, environmental stresses interfere with pulmonary immune defense mechanisms, e.g. Cigarette smoke compromises mucociliary clearance and pulmonary macrophage function Alcohol impairs neutrophil function as well as cough and epiglottic reflexes (thereby increasing the risk for aspiration), and Exposure to air pollution may impair the function of macrophages and epithelial cells.  PULMONARY IMMUNITY Bacterial pneumonias classified according to specific etiologic agent or by clinical setting in which the infection occurs. Specific clinical settings are associated with distinct group of pathogens. Thus, consideration of the clinical setting can be a helpful when antimicrobial therapy must be given empirically.  COMMUNITY ACQUIRED BACTERIAL PNEUMONIA Commonly follow viral URTI S. pnemoniae most common cause. Occurs mostly in two clinical settings: Chronic diseases such as chronic heart failure, COPD, or diabetes Congenital or acquired defects in immune responses. H. influenzae B and M. catarrhalis also common. The latter common cause for COPD exacerbation.  PATTERNS OF PNEUMONIA  PATTERNS OF PNEUMONIA “Consolidation,” used frequently, refers to “solidification” of the lung due to replacement of the air by exudate in the alveoli. Patchy consolidation of the lung is the dominant characteristic of bronchopneumonia. Consolidation of a large portion of a lobe or of an entire lobe defines lobar pneumonia. Two patterns can overlap. Organisms can produce either pattern depending on susceptibility.  LOBAR PNEUMONIA In lobar pneumonia, four stages of the inflammatory response have classically been described. First stage of congestion Lung is heavy, wet, and red. Characterized by vascular engorgement, intra-alveolar fluid with few neutrophils, and often numerous bacteria. Second stage of red hepatization Characterized by massive confluent exudation, as neutrophils, red cells, and fibrin fill the alveolar spaces. On gross examination, the lobe is red, firm, and airless, with a liverlike consistency, hence the term hepatization. Third stage of gray hepatization Marked by progressive disintegration of red cells and the persistence of a fibrinosuppurative exudate Resulting in a color change to grayish brown. In the final stage of resolution Exudate within the alveolar spaces is broken down by enzymatic digestion to produce granular, semifluid debris that is resorbed, ingested by macrophages, expectorated, or organized by fibroblasts. Extension of the pneumonia to the lung periphery often produces a pleural fibrinous reaction (pleuritis). May resolve or undergo organization, leaving fibrous thickening or permanent adhesions.  BRONCHOPNEUMONIA In bronchopneumonia there are focal areas of consolidation resulting from acute suppurative inflammation. Consolidation may be confined to one lobe but is more often multilobar and frequently bilateral and basal. Well-developed lesions are slightly elevated, dry, granular, gray-red to yellow, and poorly delimited at their margins. Histologically, a neutrophil-rich exudate fills the bronchi, bronchioles, and adjacent alveolar spaces.  COMPLICATIONS OF PNEUMONIA Tissue destruction and necrosis, causing abscess formation. Spread of infection to the pleural cavity, causing pleuritis and the intrapleural fibrinosuppurative reaction known as empyema Bacteraemic dissemination to: Heart valves Pericardium Brain Kidneys Spleen Joints Causing abscesses, endocarditis, meningitis, or suppurative arthritis.  CLINICAL FEATURES The major symptoms of typical community-acquired acute bacterial pneumonia are: Abrupt onset of high fever Shaking chills Cough producing mucopurulent sputum Occasionally, patients have hemoptysis. When pleuritis is present, it is accompanied by pleuritic pain and pleural friction rub. The whole lobe is radiopaque in lobar pneumonia, whereas there are focal opacities in bronchopneumonia. Clinical course is markedly modified by the administration of effective antibiotics. Treated patients may be afebrile with few clinical signs 48 to 72 hours after initiation of antibiotics. Identification of the organism and the determination of its antibiotic sensitivity are the keystones of therapy. Fewer than 10% of patients with pneumonia severe enough to merit hospitalization succumb Most such instances, death results from a complication, such as empyema, meningitis, endocarditis, or pericarditis, or to some predisposing influence, such as debility or chronic excess alcohol use.  COMMUNITY ACQUIRED VIRAL PNEUMONIA Prior to COVID-19 pandemic, most common causes of community-acquired viral pneumonias were Influenza types A and B Respiratory syncytial viruses Human metapneumovirus Adenovirus Rhinoviruses Rubeola virus Varicella virus  COMMUNITY ACQUIRED VIRAL PNEUMONIA During the year 2020, SARS-CoV-2, rapidly became the leading cause of community-acquired viral pneumonia in most parts of the world. All these viruses share a propensity to infect and damage respiratory epithelium, producing an inflammatory response. When the process extends to alveoli, usually interstitial inflammation, but some outpouring of fluid into alveolar spaces may also occur On chest films the changes may mimic those of bacterial pneumonia. As a result, it is not possible to distinguish bacterial and viral pneumonia based on radiologic appearance alone. Moreover, damage leading to necrosis of the respiratory epithelium inhibits mucociliary clearance \ Predisposes to secondary bacterial infections. Such serious complications of viral infection are more likely in infants, older adults, malnourished patients, individuals who are immunocompromised, and those who drink alcohol excessively.  COMMUNITY ACQUIRED VIRAL PNEUMONIA The morphologic patterns in viral pneumonias are similar. The process may be patchy or it may involve whole lobes bilaterally or unilaterally. Macroscopically, affected areas are red-blue and congested. On histologic examination: The inflammatory reaction is largely confined to the walls of the alveoli. The septa are widened and oedematous. Usually contain a mononuclear inflammatory infiltrate of lymphocytes, macrophages, and, occasionally, plasma cells. In the classic case, alveolar spaces in viral pneumonias are free of cellular exudate. In severe cases, diffuse alveolar damage with hyaline membranes may develop. In less severe, uncomplicated cases, resolution of the disease followed by reconstitution of the normal architecture. Superimposed bacterial infection results in a mixed histologic picture.  CLINICAL FEATURES The course of viral pneumonia is extremely varied. May masquerade as an URTI or “chest cold” that goes undiagnosed or manifest as a fulminant, life-threatening infection. Initial presentation usually an acute, nonspecific febrile illness characterized by fever, headache, malaise, and, later, cough with minimal sputum. In those who develop symptomatic pneumonia, the presence of the inflammatory exudate in alveolar walls prevents oxygenation of blood flowing through the affected air spaces, which in turn causes mismatch of ventilation and perfusion. As a result, the degree of respiratory distress is often out of proportion to the physical and radiographic findings.  HOSPITAL ACQUIRED PNEUMONIA Hospital-acquired, or nosocomial, pneumonias are defined as pulmonary infections acquired during a hospital stay. Not only have an adverse impact on the clinical course of ill patients but also add considerably to cost of health care. Common in patients with severe underlying disease and those who are immunosuppressed or are on prolonged antibiotic regimens. Patients on mechanical ventilation are a particularly high-risk group, and infections acquired in this setting are given the designation ventilator-associated pneumonia. Gram-negative rods (members of Enterobacteriaceae and Pseudomonas spp.) and S. aureus are the most common isolates Unlike community-acquired pneumonias, S. pneumoniae is not a common pathogen in the hospital setting.  ASPIRATION PNEUMONIA Aspiration pneumonia occurs in patients who are debilitated or those who aspirate gastric contents while unconscious (e.g., after a stroke) or during repeated vomiting. Those affected typically have abnormal gag and swallowing reflexes. Resultant pneumonia is partly chemical, due to the irritating effects of the gastric acid, and partly bacterial. Typically, more than one organism is recovered on culture, aerobes being more common than anaerobes. Often necrotizing, pursues a fulminant clinical course, and is a frequent cause of death in individuals predisposed to aspiration. In those who survive, abscess formation is a common complication. By contrast, micro-aspiration occurs in many individuals, especially those with gastroesophageal reflux, and may exacerbate other lung diseases but does not lead to pneumonia.  LUNG ABSCESS Lung abscess refers to a localized area of suppuration within the pulmonary parenchyma that results in the formation of one or more large cavities. The causative organism may be introduced into the lung by any of the following mechanisms: Aspiration of infective material from carious teeth or infected sinuses or tonsils. Aspiration of gastric contents Complication of necrotizing bacterial pneumonias Bronchial obstruction, particularly due to neoplasms, may be preceded by bronchiectasis. Septic embolism Hematogenous spread of bacteria in disseminated pyogenic infection.  LUNG ABSCESS Selectedpathogens can generate or colonize cavitary lesions and radiographically mimic lung abscess. Culprit pathogens include: Fungi (e.g., Aspergillus spp., Cryptococcus spp., Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides spp., the agents of mucormycosis), Mycobacterium tuberculosis Nontuberculous mycobacteria (e.g., M. avium, M. kansasii, M. abscessus) Parasites (e.g., Entamoeba histolytica, Paragonimus westermani, Echinococcus [hydatid cyst]). Pyogenic bacteria can also superinfect cavities caused by mycobacterial, fungal, and parasitic infections, leading to accumulation of liquid in an otherwise empty cavity. Anaerobic bacteria are present in almost all lung abscesses, and they are the exclusive isolates in one-third to two-thirds of cases.  LUNG ABSCESS Abscesses range in diameter from a few millimeters to large cavities 5 to 6 cm across. The location and number of abscesses depends on their mode of development. Pulmonary abscesses resulting from aspiration of infective material are more common on the right and usually single. Abscesses that develop in course of pneumonia or bronchiectasis are often multiple, basal, and scattered. Septic emboli and abscesses arising from hematogenous seeding commonly multiple and may affect any region of the lungs. As focus of suppuration enlarges, almost inevitably ruptures into airways. The resulting partial drainage of the abscess cavity may produce an air-fluid level on radiographic examination. Occasionally, abscesses rupture into the pleural cavity, producing bronchopleural fistulas that may result in pneumothorax or empyema. Other complications arise from embolization of septic material to the brain, giving rise to meningitis or brain abscess. On histologic examination, depending on the chronicity of the lesion, the suppurative focus is surrounded by mononuclear infiltrates (lymphocytes, plasma cells, macrophages) and variable degrees of fibrous scarring. LUNG ABSCESS  CLINICAL FEATURES Much like bronchiectasis and include a prominent cough with copious amounts of foul-smelling, purulent, or sanguineous sputum; occasionally, hemoptysis occurs. Spiking fever and malaise Clubbing of the fingers, weight loss, and anaemia may appear. Abscesses occur in 10% to 15% of patients with lung cancer; thus, when a lung abscess is found in an older adult, underlying carcinoma must be considered. Secondary amyloidosis may develop in chronic cases. Treatment includes antibiotic therapy and, if needed, surgical drainage or resection. Overall, the mortality rate is in the range of 10%.  TUBERCULOSIS Communicable chronic granulomatous disease caused by Mycobacterium tuberculosis. Mycobacteria are slender rods that are acid fast – Stain pink on Ziehl- Neelsen stain. Involves the lungs but may affect any organ or tissue in the body. WHO states that TB is most common cause of death resulting from an endemic infectious agent TB flourishes in the settings of poverty, crowding, and chronic debilitating illness. HIV infection is a dominant risk factor for the development of TB disease.  TUBERCULOSIS Important to differentiate infection from disease. Infection implies seeding of a focus with organisms, which may or may not cause clinically significant tissue damage (i.e., disease). Infection usually acquired by direct person-to-person transmission of organisms in airborne droplets from an individual with active disease to a susceptible host. In most newly infected individuals, an asymptomatic focus of pulmonary infection appears that is self- limited and, upon resolution, leaves (if anything) a tiny, fibrocalcific nodule at the site. The bacteria spreads from the primary focus to various other sites in the body but the infection remains latent. Viable organisms may remain dormant in such foci for decades and possibly for the life of the host. Such individuals are infected but do not have active disease and therefore cannot transmit organisms to others. If immune defenses are lowered, the infection may reactivate to produce communicable and potentially life-threatening disease.  PRIMARY TUBERCULOSIS Primary TB is the form of disease that develops in a previously unexposed and therefore unsensitized patient. About 5% of those newly infected develop significant disease. In the large majority of otherwise healthy individuals, the only short-term consequence of primary TB is a focus of pulmonary scarring. Uncommonly, however, this initial infection leads to progressive primary tuberculosis. This complication occurs in patients who are overtly immunocompromised or who have more subtle defects in host defenses, as is characteristic of individuals with severe acute malnutrition. The incidence of progressive primary TB is particularly high in patients who are HIV positive with significant immunosuppression (i.e., CD4 T cell counts below 200 cells/mL). Immunosuppression blunts the ability to mount a CD4 T cell-mediated response and as a result the characteristic granulomatous reaction to TB is absent.  PRIMARY TUBERCULOSIS TB almost always begins in the lungs. The inhaled bacilli usually implant in the distal air spaces of the lower part of the upper lobe or in the upper part of the lower lobe, typically close to the pleura. During the development of sensitization, a 1-cm to 1.5-cm area of gray-white consolidation appears that is called the Ghon focus. In the majority of cases, the center of this focus undergoes caseous necrosis. Tubercle bacilli, either free or within phagocytes, travel via the lymphatic vessels to the regional lymph nodes, which also often caseate. This combination of parenchymal and nodal lesions is called the Ghon complex. Lymphatic and hematogenous dissemination to other parts of the body also occurs during the first few weeks. Development of cell-mediated immunity controls the infection in approximately 95% of cases. Therefore, the Ghon complex undergoes progressive fibrosis, and calcification often follows (detectable as a Ranke complex on radiograph). Despite seeding of other organs, no lesions develop. Histologically, sites of overt infection are involved by a characteristic inflammatory reaction marked by the presence of caseating and noncaseating granulomas, which consist of epithelioid macrophages and multinucleate giant cells. In those who do not mount an effective immune response due to immunocompromise, progressive primary tuberculosis may develop. Lesions in such individuals often lack granulomas and instead consist of sheets of macrophages containing numerous bacilli  SECONDARY TUBERCULOSIS Secondary TB is pattern of disease that arises in a previously sensitized host. It may appear shortly after primary TB but more commonly arises from reactivation of dormant primary lesions many decades after initial infection, particularly when host resistance is weakened. It may also result from reinfection, which may occur either because the protection afforded by the primary disease has waned or because of exposure to a large inoculum of virulent bacilli. Whatever the source of the organisms, only a few patients (300 cells/mL) present with “usual” secondary TB (apical disease with cavitation), while those who are more significantly immunocompromised (CD4 counts below 200 cells/mL) more often present with a clinical picture that resembles progressive primary TB (lower and middle lobe consolidation, hilar lymphadenopathy, and noncavitary disease). The extent to which the patient is immunocompromised also determines the frequency of extrapulmonary involvement, rising from 10% to 15% in patients who are mildly immunocompromised to greater than 50% in those with severe immune deficiency.  SECONDARY TUBERCULOSIS The initial lesion of secondary TB is usually a small focus of consolidation, less than 2 cm in diameter, within 1 to 2 cm of the apical pleura. Such foci are sharply circumscribed, firm, gray to yellow areas with a variable amount of central caseation and peripheral fibrosis. In cases that resolve, the initial parenchymal focus undergoes progressive fibrous encapsulation, leaving only fibrocalcific scars. Histologically, active lesions show characteristic coalescent nodules with central caseation. Although tubercle bacilli can be demonstrated by appropriate methods in early exudative and caseous phases of granuloma formation, it is usually impossible to find them in the late, fibrocalcific stages.  SECONDARY TUBERCULOSIS Localized, apical, secondary pulmonary TB may heal with fibrosis either spontaneously or after therapy Or the disease may progress and extend along several different pathways. In progressive pulmonary TB, the apical lesion and the area of caseation expands. Erosion into a bronchus evacuates the caseous center, creating a ragged, irregular cavity lined by caseous material that is poorly walled off by fibrous tissue. Erosion of blood vessels results in hemoptysis. With adequate treatment, the process may be arrested, although healing by fibrosis often distorts the pulmonary architecture. Irregular cavities, now free of caseous necrosis, may remain intact or collapse and become fibrotic. If the treatment is inadequate or host defenses are impaired, the infection may spread by direct extension and by dissemination through airways, lymphatic channels, and the vascular system. Miliary pulmonary disease occurs when organisms reach the bloodstream through lymphatic vessels and then recirculate to the lung via the pulmonary arteries. The lesions appear as small (2-mm) foci of yellow-white consolidation scattered through the lung parenchyma. With progressive pulmonary TB, the pleural cavity is invariably involved and serous pleural effusions, tuberculous empyema, or obliterative fibrous pleuritis may develop.  SECONDARY TUBERCULOSIS Endobronchial, endotracheal, and laryngeal TB may develop when infective material is spread either through lymphatic channels or from expectorated infectious material. The mucosal lining may be studded with minute granulomatous lesions, sometimes apparent only on microscopic examination. Systemic miliary TB ensues when the organisms disseminate haematogenously throughout the body. Systemic miliary TB is most prominent in the liver, bone marrow, spleen, adrenal glands, meninges, kidneys, fallopian tubes, and epididymis. Isolated-organ TB may appear after hematogenous seeding to any organ or tissue and may be the presenting manifestation of TB. Relatively common sites of isolated involvement include the meninges, kidneys, adrenal glands, bones, and fallopian tubes. When the vertebrae are affected, the condition is referred to as Pott disease. Paraspinal “cold” abscesses may extend along the tissue planes to present as an abdominal or pelvic mass.  SECONDARY TUBERCULOSIS Lymphadenitis is the most frequent form of extrapulmonary TB, usually occurring in the cervical region (“scrofula”). Lymphadenopathy tends to be unifocal, and most patients do not have concurrent extranodal disease. Patients who are HIV positive almost always have multifocal disease, systemic symptoms, and either pulmonary or other organ involvement by active TB. In years past, intestinal TB contracted by drinking contaminated milk was common as a primary focus of TB. In higher-income countries today, intestinal TB is more often a complication of protracted advanced secondary TB, occurring due to the swallowing of coughed-up infective material. Typically, the organisms are trapped in mucosal lymphoid aggregates of the small and large bowel, which then undergo inflammatory enlargement with ulceration of the overlying mucosa, particularly in the ileum.  CLINICAL FEATURES Localized secondary TB may be asymptomatic. When manifestations appear, they are usually insidious in onset, with gradual development of both systemic and localizing symptoms and signs. Systemic manifestations related to the release of cytokines by activated macrophages (e.g., TNF and IL-1) often appear early in the disease course and include malaise, anorexia, weight loss, and fever. Commonly, the fever is low grade and remittent (appearing late each afternoon and then subsiding) and is often accompanied by night sweats. With progressive pulmonary involvement, increasing amounts of sputum, at first mucoid and later purulent, appear. When cavitation is present, the sputum contains tubercle bacilli. Some degree of hemoptysis is present in about half of pulmonary TB cases. Pleuritic pain may result from extension of the infection to the pleural surfaces. Extrapulmonary manifestations of TB are legion and depend on the organ system involved (e.g., tuberculous salpingitis may present as infertility, tuberculous meningitis with headache and neurologic deficits, spine involvement [Pott disease] with back pain and paraplegia).  CLINICAL FEATURES The diagnosis of pulmonary disease is based in part on the history and on physical and radiographic findings of consolidation or cavitation in the apices of the lungs. Ultimately, however, tubercle bacilli must be identified. The most common method for diagnosis of active mycobacterial infection remains detection of organisms in sputum by acid- fast staining or by staining with fluorescent auramine rhodamine. Conventional cultures for mycobacteria require up to 10 weeks, but liquid media-based radiometric assays that detect mycobacterial metabolism are able to provide an answer within 2 weeks. PCR amplification can be performed on liquid growth media, as well as on tissue sections, to identify the mycobacterium. However, culture remains the standard diagnostic modality because it can identify the occasional PCR-negative case and also allows testing of drug susceptibility. Of concern, multidrug resistance (MDR), defined as resistance of mycobacteria to two or more of the primary drugs used for treatment of TB, is becoming more common, and the WHO estimated that 465,000 individuals had multidrug-resistant TB in 2019, representing approximately 3% of new cases and 20% of previously treated cases. The epicenter of this troubling development lies in Eastern Europe, Russia, several areas of Africa, and parts of Asia, regions where up to 20% of new infections are with multidrug-resistant strains. Of even greater concern, approximately 5% to 10% of such cases exhibit extensive multidrug resistance, defined by resistance to many of the antibiotics in current use against TB. The prognosis is determined by the extent of the infection (localized versus widespread), the immune status of the host, and the antibiotic sensitivity of the organism. The prognosis is guarded in those with multidrug-resistant TB. Amyloidosis may develop in persistent cases.  REFERENCE Robbins and Cotran – Basic Pathology 11th ed. 2022 QUESTIONS?