Fungal Diseases Study Notes (Ch. 18 & 19)

Fungal Diseases — Key Concepts and Pathophysiology

  • Fungal diseases are caused by inhaled fungal spores and can produce a frothy, yeast-like substance that triggers an inflammatory response similar to pneumonia.

    • In later stages, presentations may resemble tuberculosis (TB).
    • They often lead to a chronic restrictive lung disorder, with upper lobes affected most commonly.

  • Anatomic alterations of the lung seen with fungal infections include:

    • Alveolar consolidation
    • Alveolar-capillary destruction
    • Caseous tubercles or granulomas
    • Cavity formation
    • Fibrosis of the lung parenchyma
    • Bronchial airway secretions

  • Major categories of fungal pathogens:

    • Primary “True” Pathogens:
    • Histoplasmosis
    • Coccidioidomycosis
    • Blastomycosis
    • Secondary “Opportunistic” pathogens (opportunistic fungi that typically do not cause disease in healthy individuals):
    • Candida albicans (thrush)
    • Cryptococcus neoformans
    • Aspergillus

  • Histoplasmosis (Histoplasma capsulatum)

    • Most common fungal disease in the U.S.
    • Prevalence highest along major river valleys of the Midwest; also known as Ohio Valley Fever.
    • Found in soils rich with bird and/or bat excrement; birds do not carry the organism, although spores may be carried by bats.
    • Forms:
    • Asymptomatic histoplasmosis (most common)
    • Acute symptomatic pulmonary histoplasmosis (presents like pneumonia on symptoms and chest X-ray)
    • Chronic pulmonary histoplasmosis (signs/symptoms resemble TB)
    • Disseminated histoplasmosis (often in immunocompromised individuals; can affect nearly any body part)

  • Histoplasmosis Screening and Diagnosis

    • Fungal culture is the gold standard but grows over ~4 weeks; not ideal in disseminated disease due to potential delays in treatment.
    • Fungal stain from sputum sample can be used; a positive test is highly accurate, but obtaining sputum may be difficult.
    • Serology checks blood serum for antigens and antibodies; relatively fast and accurate but false negatives can occur.

  • Blastomycosis (Blastomyces dermatitidis)

    • Occurs in the south-central and midwestern U.S. and Canada; also called Chicago Disease, Gilchrist’s disease, and American blastomycosis.
    • Habitat includes forest soils, decaying wood, animal manure, and abandoned buildings with high organic matter.
    • Epidemiology: more common in pregnant women and middle-aged African American men; also affects cats, dogs, and horses.

  • Blastomycosis Clinical Manifestations

    • Acute illness resembles acute histoplasmosis; however, cough is frequently productive with purulent sputum.
    • With progression, nodules and abscesses form in the lungs.
    • Extrapulmonary lesions may involve skin, bones, reproductive tract, spleen, liver, kidney, or prostate gland.
    • Skin lesions may be the first sign of disease.

  • Blastomycosis Diagnosis

    • Direct visualization of yeast in sputum smears.
    • Culture of the organism can be performed.
    • Skin tests are not accurate for diagnosis.

  • Coccidioidomycosis (Coccidioides immitis)

    • Inhalation of spores; endemic in hot, dry regions (California, Arizona, Nevada, New Mexico, Texas, Utah).
    • Also known as Valley Fever, Desert Fever, San Joaquin Valley Fever, California Disease.

  • Coccidioidomycosis Clinical Manifestations

    • About 60% of individuals with a positive skin test are asymptomatic; the remaining 40% may have cold-like symptoms.
    • Chronic progression features nodular growths (fungomas) and cavity formation.
    • Dissemination occurs in ~1:6000 cases.
    • Skin lesions are commonly accompanied by arthritis, particularly in the ankles and knees (described as Desert bumps, Desert arthritis, Desert rheumatism).

  • Coccidioides immitis Screening and Diagnosis

    • Skin test: a positive result indicates prior or current immune response to the fungus.
    • Direct visualization of spherules in sputum, tissue exudates, biopsy, or spinal fluid.
    • Blood tests detect antibodies to the fungus.
    • Culture of the organism from infected fluid or tissue.

  • Fungal Diseases — Clinical Manifestations (General TB-like presentation and signs)

    • Increased respiratory rate (RR), heart rate (HR), and blood pressure (BP)
    • Chest pain and decreased chest expansion
    • Cyanosis, digital clubbing
    • Peripheral edema and venous distention due to polycythemia/cor pulmonale
    • Cough with sputum production and hemoptysis
    • Chest examination: increased tactile and vocal fremitus; dull percussion; bronchial breath sounds; crackles; wheezing; pleural friction rub if pleural surface is involved; whispered pectoriloquy

  • Pulmonary Function Test Findings in Moderate to Severe Fungal Disease (Restrictive Lung Pathophysiology)

    • Flow and volume measurements typically show restriction:
    • FVC ↓; FEV1 ↓; FEV1/FVC ratio often normal or ↑
    • FEF25-75 ↓; FEF50% ↓; FEF200-1200 ↓; PEFR ↓; MVV ↓
    • Lung volume measures:
    • VT ↓; IRV ↓; ERV ↓; RV ↓; VC ↓; IC ↓; FRC ↓; TLC ↓
    • RV/TLC ratio variable

  • Arterial Blood Gases in Moderate Fungal Disease

    • Acute alveolar hyperventilation with hypoxemia (Acute Respiratory Alkalosis):
    • extpHextupext{pH} ext{ up}, extPaCO<em>2extdownext{PaCO}<em>2 ext{ down}, extHCO</em>3−extnearnormalext{HCO}</em>3^- ext{ near normal}, extPaO<em>2extdownext{PaO}<em>2 ext{ down}, extSaO</em>2/extSpO2extdownext{SaO}</em>2/ ext{SpO}_2 ext{ down}
    • PaO2 and PaCO2 trends during acute alveolar hyperventilation are shown in illustrative figure (Section 21).

  • Arterial Blood Gases in Severe Fungal Disease with Pulmonary Fibrosis

    • Chronic ventilatory failure with hypoxemia (compensated respiratory acidosis):
    • extpHextnearnormalorslightlylowext{pH} ext{ near normal or slightly low}, extPaCO<em>2extupext{PaCO}<em>2 ext{ up}, extHCO</em>3−extupext{HCO}</em>3^- ext{ up}, extPaO<em>2extdownext{PaO}<em>2 ext{ down}, extSaO</em>2/extSpO2extdownext{SaO}</em>2/ ext{SpO}_2 ext{ down}

  • Acute vs. Chronic Ventilatory Failure (Arterial Blood Gases)

    • Acute ventilatory changes can be superimposed on chronic ventilatory failure:
    • Potential dangerous ABG patterns include acute alveolar hyperventilation on chronic failure and impending acute ventilatory failure.
    • Acute ventilatory failure (acute hypoventilation) may be superimposed on chronic ventilatory failure.

  • Radiologic Findings (Chest Radiograph)

    • Increased opacity (infiltrates)
    • Cavity formation
    • Pleural effusion
    • Calcification and fibrosis
    • Right ventricular enlargement

  • Imaging Examples (Figures)

    • Fig. 18-1: Cross-sectional view of alveoli infected with Histoplasma capsulatum showing AC (alveolar consolidation), S (spore), M (alveolar macrophage), YLS (yeast-like substance).
    • Fig. 18-2: Acute inhalational histoplasmosis with bilateral hilar adenopathy and diffuse nodular opacities in a healthy patient after exposure.
    • Fig. 18-3: Histoplasmoma with a well-defined round nodule and central calcification.
    • Fig. 18-4: Chronic cavitary histoplasmosis with marked upper-lung predominance and large cavities.

  • Pharmacologic Treatment

    • Amphotericin B is the treatment of choice for most fungal infections.
    • Due to significant nephrotoxicity, azole antifungal agents are common alternatives:
    • Ketoconazole
    • Fluconazole
    • Itraconazole
    • Echinocandins (new class of antifungals)
    • Nystatin is used to treat Candida albicans infections (thrush)

  • Respiratory Care Treatment Protocols

    • Oxygen Therapy Protocol
    • Bronchopulmonary Hygiene Therapy Protocol
    • Mechanical Ventilation Protocol

  • Connections to Foundations and Real-World Relevance

    • Fungal infections often present with TB-like symptoms and a restrictive pattern on PFTs, highlighting the need to consider fungal etiologies in endemic areas or after environmental exposure.
    • Diagnostic delays (e.g., culture growth) can be critical in disseminated disease, underscoring the importance of rapid serology and direct visualization where possible.
    • Radiologic findings (cavities, upper-lobe predominance) can mimic TB, but epidemiology and organism characteristics guide management.
    • Management balances efficacy and toxicity ( Amphotericin B nephrotoxicity → switch to azoles when feasible ); adoption of newer antifungals (echinocandins) reflects evolving therapeutic options.

  • Ethical, Philosophical, and Practical Implications

    • Exposure history and occupational/environmental risk are critical for diagnosis and prevention.
    • In endemic regions, clinicians must balance empirical treatment against potential drug toxicities and resistance patterns.
    • Resource availability (culture turnaround time, imaging access, serology tests) influences diagnostic strategies and patient outcomes.