Pathophys 1 Exam 3 ( TUBERCULOSIS AND OTHER INFECTIOUS DISEASES)

Tuberculosis

uInfection caused by Mycobacterium tuberculosis, an acid-fast bacillus

uLeading cause of death from a curable infectious disease throughout the world

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Mycobacterium tuberculosis Overview

• Acid-fast bacillus with mycolic acid cell wall

• Slow-growing, intracellular pathogen

• Resistant to desiccation and common disinfectants

Epidemiology of TB

• High prevalence in Africa, Asia

• Risk groups: immunosuppressed, homeless, healthcare workers

• Rising multi-drug resistant (MDR) and extensively drug-resistant (XDR) TB strains

TB Transmission

• Inhalation of droplet nuclei

• Requires prolonged close contact

• Bacilli reach alveoli and are phagocytosed

Tuberculosis Transmission and Infection

Tranmitted by inhalation of respiratory droplets

requires prolonged close contact

Bacilli reach alveoli and are phagocytosed

Tubercle formation: Granulomatous lesion

-Isolation of bacilli by enclosing them in tubercles and surrounding the tubercles with scar tissue

Caseous necrosis: Cheeselike material

May remain dormant for life or cause active disease

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Immune Response to TB

• Cell-mediated immunity essential

• Activation of macrophages by IFN-gamma

• Granuloma formation contains infection

Granuloma Formation

• Central necrosis surrounded by epithelioid cells, lymphocytes

• Caseating necrosis hallmark of TB

• May calcify or cavitate

Caseating Necrosis

• Cheese-like necrosis due to hypoxia and immune attack

• Diagnostic of TB in histology

• Associated with cavitary lesions

Primary TB Infection

• Formation of Ghon focus and Ghon complex

• Most cases resolve or become latent

• Initial immune containment by macrophages and T cells

Latent vs. Active TB

• Latent: positive test, no symptoms, non-contagious

• Active: symptomatic, contagious, radiologic abnormalities

Tuberculosis : uClinical manifestations

Latent tuberculosis infection: Asymptomatic

Fatigue, weight loss, lethargy, anorexia (loss of appetite), a low-grade fever that usually occurs in the afternoon, and night sweats; purulent cough

Tuberculosis : Diagnosis

Positive tuberculin skin test (TST) a purified protein derivative (PPD): Does not differentiate past, latent, or active disease

Sputum culture, immunoassays, indirect drug susceptibility testing

Chest radiographs

Extrapulmonary TB

• TB lymphadenitis (scrofula), CNS TB (meningitis), miliary spread

• Bone (Pott's disease), GI, genitourinary TB

• More common in immunocompromised

Reactivation TB

• Occurs when immunity wanes (HIV, steroids)

• Apical lung involvement due to higher oxygen tension

• Constitutional symptoms and productive cough

Progressive Primary TB

• Failure of immune containment

• Seen in young children and immunosuppressed

• Dissemination to hilar nodes and bloodstream

Miliary TB Pathophysiology

• Hematogenous dissemination of bacilli

• Tiny nodules throughout lung fields

• High mortality if untreated

TB in Immunocompromised

• Often lacks typical granulomas

• More extrapulmonary involvement

• May require biopsy and PCR for diagnosis

TB-HIV Coinfection

• Rapid progression and atypical presentation

• Overlapping toxicity of treatments

• Higher risk of MDR-TB

Radiographic and Histologic Findings

• CXR: upper lobe cavitation, lymphadenopathy

• Histology: granulomas with caseation

• Ziehl-Neelsen stain shows acid-fast bacilli

Sputum Testing

• Three early morning samples recommended

• AFB smear: rapid but low sensitivity

• Culture: gold standard, takes weeks

NAAT and Molecular Tests

• GeneXpert MTB/RIF: rapid TB and rifampin resistance

• PCR-based assays detect DNA

• Useful in smear-negative, HIV-positive patients

Anti-TB Drugs

• Isoniazid: inhibits mycolic acid synthesis

• Rifampin: inhibits RNA polymerase

• Pyrazinamide: effective in acidic pH

• Ethambutol: inhibits cell wall synthesis

TB Treatment Regimens

• Intensive phase (2 months): RIPE

• Continuation phase (4-7 months): INH + RIF

• Adherence crucial to prevent resistance

Tuberculosis : Treatment

Isoniazid, rifampin, pyrazinamide, and ethambutol

Drug-resistant bacilli: Combination of at least four drugs to which the microorganism is susceptible, administering for 18 months

--Review drug effectiveness at 6 months.

MDR-TB TX

• Resistant to at least INH and RIF

• Requires second-line agents: fluoroquinolones, injectables

• Longer duration and more toxic regimen

Public Health Measures

• DOT: directly observed therapy

• Contact tracing and screening

• TB control programs and vaccination (BCG)

TB Test Interpretation

• >5mm induration: positive in immunocompromised

• >10mm: positive in healthcare workers

• >15mm: positive in general population

Pneumonia

infection of the lower respiratory tract

Responsible for more disease and death than any other infection

community-acquired pneumonia

--Streptococcus pneumoniae

Nosocomial pneumonia

--hospital-acquired

--Ventilator-associated pneumonia

Pneumonia: Routes of infection

aspiration

inhalation

endotracheal tubes and suctioning

bacteremia in lungs

respiratory defenses cannot destroy the microorganism

Type of pneumonia

pneumococcal pneumonia

Viral pneumonia : -Most common form is influenza

Pathogen Entry and Transmission

• Inhalation of airborne droplets or spores

• Aspiration of oropharyngeal contents

• Hematogenous spread from distant sites

• Direct extension from contiguous structures

Immune Response to Inhaled Pathogens

• Recognition by pattern recognition receptors (PRRs)

• Activation of innate immunity

• Recruitment of neutrophils and macrophages

• Release of cytokines and chemokines

Inflammation and Alveolar Damage

• Inflammatory infiltrate disrupts alveolar architecture

• Increased capillary permeability → alveolar flooding

• Surfactant inactivation and atelectasis

Hypoxemia and Impaired Gas Exchange

• Shunting and V/Q mismatch

• Decreased diffusion capacity due to edema

• Hypoxemia leads to increased respiratory effort

Cytokine Storm and Systemic Effects

• Dysregulated immune response

• High levels of IL-6, TNF-alpha, and others

• Capillary leak syndrome, hypotension, multiorgan failure

Acute vs. Chronic Pulmonary Infections

• Acute: sudden onset, short duration, exudative phase

• Chronic: prolonged, granuloma formation, fibrosis

• Examples: CAP vs. TB or fungal infections

Pneumonia : Clinical Manifestations

uPreceded by an upper respiratory infection

uCough, dyspnea, and fever

uChills, malaise, and pleuritic chest pain

Pneumonia Treatment approach

Prevention of aspiration

Respiratory isolation of immunocompromised individuals

Vaccination for appropriate populations

Reduction of ventilator-associated pulmonary infections through a variety of oral hygiene and endotracheal tube interventions

Establishment of adequate ventilation and oxygenation

May require mechanical ventilation

Adequate hydration

Good pulmonary hygiene (e.g., deep breathing, coughing, chest physical therapy)

Bacterial pneumonia: Antibiotics

Viral pneumonia: Supportive therapy alone, unless secondary bacterial infection is present

Severe cases: Antiviral medications and/or antifungal, multiple drugs

Sputum Analysis and Microbiologic Testing

• Gram stain and culture

• AFB smear and culture for TB

• PCR and multiplex panels for rapid ID

Bacterial Pneumonia

• Community-acquired vs. healthcare-associated

• Common organisms: S. pneumoniae, H. influenzae, Legionella

• Pathogenesis: alveolar invasion → exudate formation

• Clinical: fever, productive cough, pleuritic chest pain

Streptococcus pneumoniae

• Gram-positive diplococcus

• Virulence factors: capsule, pneumolysin

• Lobar consolidation on imaging

• Rust-colored sputum, positive urine antigen test

Klebsiella, Pseudomonas, MRSA

• Klebsiella: thick, mucoid sputum; cavitating pneumonia

• Pseudomonas: common in CF, ventilator-associated infections

• MRSA: necrotizing pneumonia, empyema risk

Atypical Bacteria

• Mycoplasma pneumoniae: walking pneumonia, extrapulmonary signs

• Chlamydia pneumoniae: slow onset, pharyngitis

• Legionella: high fever, GI symptoms, hyponatremia

Viral Pneumonia

• Influenza, RSV, adenovirus, SARS-CoV-2

• Direct cytopathic effects and immune-mediated injury

• Diffuse alveolar damage, ground-glass opacities

Pathophysiology of Viral Lung Injury

• Viral replication → epithelial cell death

• Disruption of tight junctions

• Induction of pro-inflammatory cytokines

Fungal Infections

• Histoplasmosis: inhaled spores, granulomas in immunocompetent

• Coccidioidomycosis: desert exposure, nodular infiltrates

• Aspergillus: invasive disease in neutropenic patients

Immunocompromised Host Infections

• Broad range of pathogens including PCP, CMV

• Atypical presentations and rapid progression

• Requires aggressive diagnostics and empiric therapy

Aspiration Pneumonia

• Entry of gastric/oropharyngeal contents

• Mixed flora: anaerobes, streptococci

• Seen in altered mental status, stroke, intoxication

Necrotizing Pneumonia and Empyema

• Tissue necrosis and liquefaction

• Complication of severe bacterial infection

• Empyema: pus in pleural space, requires drainage

Nosocomial Infections

u• ICU and ventilator-associated pneumonia

u• Biofilm formation, MDR organisms

u• Prevention: hand hygiene, VAP bundles

Abscess Formation and Cavitation: Abscess

Circumscribed area of suppuration and destruction of lung parenchyma

Follows consolidation of lung tissue, in which inflammation causes alveoli to fill with fluid, pus, and microorganisms.

Necrosis (death and decay) of consolidated tissue: abscess empties into the bronchus, leaving a cavity

Cavitation: Process of abscess emptying and cavity formation

Most common cause: Aspiration

Abscess Formation and Cavitation : Clinical Manifestations

Fever, cough, chills, sputum production, and pleural pain

Bronchus involvement: Severe cough, copious amounts of often foul-smelling sputum, and occasionally hemoptysis

Abscess Formation and Cavitation : Treatment

Antibiotics

Chest physical therapy, including chest percussion and postural drainage

Bronchoscopy: To drain the abscess