Makindo Medical Notes

Related Subjects: |Bacteria and their Infections |Viruses and their Infections |Fungi and their infections

About

• Fungi are eukaryotic organisms that can be divided into:
  • Yeasts: Unicellular growth forms of fungi, commonly used in bread-making. Yeast cells are spherical to elliptical and reproduce through budding.
  • Moulds: Multicellular fungi that grow as filamentous structures called hyphae. Hyphae are threadlike, branching tubules composed of fungal cells attached end to end. Moulds can often be seen growing on food with a characteristic green or white fuzzy appearance due to the hyphal growth.
  • Dimorphic fungi: These fungi can switch between yeast and mould forms depending on environmental conditions (e.g., temperature). In humans, they tend to exist as yeasts at body temperature and moulds in the environment.

Ergosterol

• Fungal cell membranes contain a steroid called ergosterol, which is analogous to cholesterol in human cell membranes.
• This difference in membrane composition can be exploited to develop antifungal drugs.
• Imidazoles (e.g., ketoconazole, clotrimazole) inhibit ergosterol synthesis and are generally fungistatic, meaning they inhibit fungal growth.
• Amphotericin B and nystatin bind to ergosterol, disrupting fungal cell membrane integrity and leading to cell death. These drugs are fungicidal.

Cell Walls

• Fungal cell walls are composed of complex carbohydrates, including glucans, mannans, and chitin, which provide structural integrity.
• Echinocandins (e.g., caspofungin) block glucan synthesis, leading to a weakened cell wall and fungal cell death.

Structure

• Filaments (Hyphae): Multicellular fungal structures that grow into mould colonies.
• Single-cell budding (Yeast): Yeasts reproduce by budding and are unicellular forms of fungi.
• Dimorphic Fungi: Capable of existing in both yeast and mould forms depending on environmental conditions.

Fungal Disease

• Dermatophytes:
  • Fungi that infect the skin, hair, and nails. They live in keratin-rich outer layers of the skin, where they secrete an enzyme called keratinase that partially digests keratin, leading to hair loss, scaling of the skin, and nail crumbling.
  • When the nails are involved, this is called onychomycosis, resulting in thickened, discolored, and brittle nails. Onychomycosis becomes more common with age.
  • Superficial infections may present as tinea with a ring-like shape, often referred to as "ringworm." Specific types include:
    • Tinea capitis: Affects the scalp.
    • Tinea pedis: Affects the feet, causing athlete’s foot, which leads to cracking and peeling between the toes.
• Candidal Infection (Candidiasis):
  • Caused by overgrowth of Candida, particularly Candida albicans, often seen after the use of antibiotics or steroids, which disrupt normal flora.
  • Typically causes red, raw, painful mucosal surfaces in the mouth (thrush) or genitals, and diaper rash in infants.
  • Disseminated candidiasis occurs in immunocompromised patients or those with intravenous lines/catheters, leading to systemic infections that require systemic therapy.
• Disseminated Fungal Infections: These infections typically affect immunocompromised individuals and require systemic antifungal therapy.
  • Histoplasmosis: Dimorphic fungus found in soil, particularly in the Mississippi and Ohio River valleys. Associated with exposure to bird or bat droppings. Presents as a persistent chest infection and can disseminate to the brain, liver, or spleen.
  • Blastomycosis: Dimorphic fungus found in the same regions as histoplasmosis. Causes chronic pulmonary infection and may disseminate to the skin, bones, or genitourinary tract.
  • Coccidioidomycosis (Valley Fever): Dimorphic fungus found in the southwestern U.S. (Arizona, New Mexico, Southern California). Can cause flu-like symptoms, persistent chest infection, and rarely disseminates to the brain or bones.
• Cryptococcus neoformans: Found in soil and bird droppings, particularly pigeon droppings. Inhalation can lead to pulmonary infections or, in immunocompromised patients, life-threatening cryptococcal meningitis.
• Allergic Fungal Disease:
  • Allergic bronchopulmonary aspergillosis (ABPA): A hypersensitivity reaction to Aspergillus species in patients with asthma or cystic fibrosis, leading to worsening respiratory symptoms.
  • Farmer's lung: A hypersensitivity pneumonitis caused by repeated exposure to fungal spores in hay or grain dust.

Fungal Infections