11.3 Pulmonary Infections, Neoplasms & Respiratory Pharmacology

11.3 Pulmonary Infections, Neoplasms & Respiratory Pharmacology

Quick Answer: Pneumonia patterns follow organism and host (lobar typical, interstitial atypical, dependent aspiration). TB pathogenesis runs Ghon complex → latency → apical reactivation with caseation. Lung cancers split by histology, location, smoking link, and paraneoplastics; mesothelioma is asbestos-related pleural malignancy. Pharm targets β2, M3, inflammation, leukotrienes, IgE, and PDE; know O2 free-radical toxicity and CO–Hb mechanisms.

Infectious, neoplastic, and pharmacologic pulmonary content on the CBSE rewards pattern recognition tied to mechanism—organism virulence, immune granuloma formation, oncogenic associations, and receptor-level drug action.

Pneumonia Patterns and Organism Mechanisms

Typical (lobar/bronchopneumonia) patterns

Streptococcus pneumoniae is the classic lobar pneumonia pathogen: lancet-shaped gram-positive diplococci with a polysaccharide capsule that inhibits phagocytosis. Stages of lobar pneumonia (congestion → red hepatization → gray hepatization → resolution) are still tested as morphologic evolution. Staphylococcus aureus causes bronchopneumonia and abscesses, important post-viral (influenza) and in IV drug use (hematogenous septic emboli). Klebsiella (currant-jelly sputum teaching image) affects alcoholics and diabetics with upper-lobe consolidation and abscess tendency; thick capsule. Haemophilus influenzae and Moraxella appear in COPD exacerbations and community pneumonia contexts. Pseudomonas is a classic nosocomial and CF pathogen with biofilm and toxin virulence.

Atypical patterns

Atypical pneumonias often produce interstitial or patchy infiltrates, nonproductive cough, and extrapulmonary clues. Mycoplasma pneumoniae: no cell wall (β-lactams ineffective), membrane with sterols, walking pneumonia in young adults; cold agglutinins (IgM) are a classic association; can cause erythema multiforme/SJS-spectrum skin findings. Chlamydophila pneumoniae and Chlamydia psittaci (birds) are intracellular. Legionella pneumophila: water aerosols, hyponatremia, GI symptoms, neurologic findings; silver stain/charcoal yeast extract culture teaching points; intracellular macrophage survival. Viral pneumonias (influenza, RSV, etc.) damage epithelium and predispose to bacterial superinfection.

Aspiration pneumonia

Aspiration favors dependent lung segments: upright—lower lobes (often right); supine—posterior upper lobes/superior lower lobes. Mixed oral anaerobes and aerobes; chemical pneumonitis from acid can precede infection. Risk: altered consciousness, dysphagia, alcohol, anesthesia.

Tuberculosis Pathogenesis

Mycobacterium tuberculosis is an acid-fast (mycolic acid cell wall), aerobic bacillus transmitted by droplets. It survives within macrophages by inhibiting phagosome–lysosome fusion. Cord factor (trehalose dimycolate) contributes to virulence and serpentine growth. Primary infection often mid/lower zones: Ghon focus plus hilar node involvement = Ghon complex; Ranke complex when calcified/healed. Most hosts contain infection via Th1/IFN-γ macrophage activation and granuloma formation; organisms may remain dormant.

Secondary (reactivation) TB classically involves apical/posterior upper lobes (higher PO2). Caseating granulomas, cavitation, and person-to-person infectiousness rise when necrosis communicates with airways. Miliary TB is hematogenous seeding. Progressive primary disease occurs in immunocompromise. PPD/IGRA measure immune memory, not active vs latent disease by themselves; false negatives in anergy. Caseous necrosis is the histologic hallmark of mycobacterial (and some fungal) granulomatous disease.

Lung Cancer: Types, Associations, Paraneoplastics

Primary lung cancers are still often taught in four major histologic buckets (with adenocarcinoma dominance in modern epidemiology).

Adenocarcinoma

Most common overall and most common in nonsmokers and women; typically peripheral. Arises from glandular epithelium; may associate with EGFR, ALK, KRAS, and other driver mutations in molecular teaching. Can present as scar carcinoma or along pneumocyte lineage (including formerly BAC-pattern lepidic growth concepts). Hypertrophic osteoarthropathy can appear.

Squamous cell carcinoma

Strongly smoking-related, often central, from bronchial metaplasia → dysplasia → CIS → invasion. Keratin pearls and intercellular bridges. PTHrP → hypercalcemia is the classic paraneoplastic. Cavitation is relatively common.

Small cell (oat cell) carcinoma

Strongly smoking-related, central, neuroendocrine origin (Kulchitsky-like cells), high N/C ratio, molding, extensive necrosis, early metastasis. Almost always treated as systemic disease. Paraneoplastics: ACTH (Cushing), ADH/SIADH (hyponatremia), Lambert–Eaton myasthenic syndrome (presynaptic Ca2+ channel antibodies → proximal weakness improving transiently with use). Myc amplification is a classic molecular association in teaching.

Large cell carcinoma

Undifferentiated epithelial malignancy, often peripheral, diagnosis of exclusion among non-small cell types after ruling out adeno/squamous features; can produce gynecomastia/β-hCG in rare paraneoplastic teaching notes. Aggressive.

Metastases to lung are more common than primary tumors in many autopsy series; cannonball metastases suggest renal cell or other vascular primaries. Pancoast (superior sulcus) tumors cause shoulder pain, Horner syndrome, and brachial plexus findings—often NSCLC. SVC syndrome more classic with central small cell or other central masses.

Mesothelioma

Malignant mesothelioma arises from mesothelial cells, most often pleura, and is strongly associated with asbestos (amphibole fibers especially). Latency is long (decades). Smoking is not a major synergistic risk for mesothelioma the way it is for asbestos-related bronchogenic carcinoma (smoking × asbestos multiplies lung cancer risk). Pathologically, mesothelioma can be epithelioid, sarcomatoid, or biphasic; encases the lung. Recurrent hemorrhagic effusions appear clinically. Do not confuse pleural plaques (benign asbestos marker) with mesothelioma.

Respiratory Pharmacology Concepts

Bronchodilators

β2-agonists (albuterol short-acting; salmeterol/formoterol long-acting) raise cAMP via Gs → protein kinase A → bronchial smooth muscle relaxation. Tremor, tachycardia, hypokalemia are mechanism-based adverse effects. Anticholinergics (ipratropium, tiotropium) block M3-mediated bronchoconstriction and reduce secretions; especially useful in COPD. Combined β2 + anticholinergic is additive.

Anti-inflammatory and controller agents

Inhaled corticosteroids reduce transcription of inflammatory genes, decrease eosinophilic inflammation, and are cornerstone controllers in persistent asthma; thrush and dysphonia are local adverse effects (rinse mouth). Systemic steroids for exacerbations.

Leukotriene modifiers: montelukast/zafirlukast block CysLT1 receptors; zileuton inhibits 5-lipoxygenase. Useful in aspirin-exacerbated respiratory disease and exercise-induced pathways where leukotrienes dominate.

Theophylline: nonselective phosphodiesterase inhibition → ↑cAMP; also adenosine receptor antagonism. Narrow therapeutic index (seizures, arrhythmias); CYP interactions (e.g., with cimetidine, macrolides, ciprofloxacin raising levels).

Anti-IgE (omalizumab): monoclonal antibody binding free IgE, reducing FcεRI-mediated mast cell activation in allergic asthma. Other biologics target IL-5/IL-5R or IL-4R pathways in eosinophilic phenotypes—mechanism class knowledge matters more than brand lists.

Supportive toxicology: O2 and CO

Oxygen toxicity with prolonged high FiO2 relates to reactive oxygen species overwhelming antioxidant defenses (superoxide dismutase, catalase, glutathione), injuring capillary endothelium and alveolar epithelium—can contribute to absorption atelectasis and free-radical lung injury. Neonatal concerns include retinopathy of prematurity and bronchopulmonary dysplasia links with oxygen/ventilator injury teaching.

Carbon monoxide poisoning: CO binds Hb with affinity ~200–250× O2, forms carboxyhemoglobin, left-shifts the O2 curve, and impairs unloading; also binds cytochrome oxidase impairing cellular respiration. PaO2 (dissolved) may be normal; pulse oximetry can be falsely reassuring depending on device; co-oximetry measures COHb. Treatment concept: 100% O2 shortens CO half-life; hyperbaric O2 in severe cases further accelerates elimination.

Integrated Clinical Snapshots

College student, dry cough, cold agglutinins → Mycoplasma. Alcoholic with upper-lobe cavitation and currant-jelly sputum → Klebsiella. Apical cavitary disease years after primary exposure → reactivation TB. Central mass, smoker, hyponatremia → small cell + SIADH. Peripheral mass in nonsmoker → adenocarcinoma until proven otherwise. Shipbuilder, pleural encasement → mesothelioma; shipbuilder who also smokes with parenchymal mass → think bronchogenic carcinoma risk amplification from asbestos + smoking. Severe allergic asthma not controlled on ICS/LABA → consider anti-IgE mechanism.

Mastery check: if you can match pneumonia pattern to organism virulence, narrate TB from Ghon complex to apical caseation, assign lung tumor histology to location/paraneoplastic pairs, separate mesothelioma from asbestos-plus-smoking carcinoma risk, and place each respiratory drug on its receptor/enzyme target—including CO vs O2 toxicity—you have the CBSE core of this section.