medical mastermind community€¦ · web viewc. albicans yeasts form germ tubes at 37 c in serum...

USMLE Step 1 Web Prep — Medically Important Fungi131190 >>> 0:00:00.2

SLIDE 1 of 66Mycology is the study of fungi (molds, yeasts, and mushrooms) Eukaryotic (e.g., true nucleus, 80S ribosomes, mitochondria, as are humans) Complex carbohydrate cell walls: chitin, glucan, and mannan Ergosterol :Imidazole antifungals inhibit synthesis of ergosterol

Fungal Morphology Hyphae = Filamentous Cellular Units of Molds and Mushrooms Nonseptate Hyphae

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Fungal Morphology Septate Hyphae With cross walls Width is fairly regular (tube-like)

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Hyphal Coloration Dematiaceous: Dark colored (gray, olive, brown, black) Hyaline: Clear

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Fungal Morphology Yeasts = Single Celled (Round To Oval) Fungi

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Dimorphic Fungi Fungi able to convert from hyphal to yeast or yeast-like forms Thermally dimorphic: In the "cold" are the mold form Histoplasma Blastomyces Coccidioides Sporothrix

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Pseudohyphae (Candida albicans): Hyphae with constrictions at each septum

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Spore Types:

Conidia Asexual spores Formed off of hyphae Common Airborne

Blastoconidia

“Buds” on yeasts (asexual budding daughter yeast cells)

Arthroconidia Asexual spores formed by a “joint.”

Spherules and Endospores (Coccidioides) Spores inside the spherules in tissues

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Spore Types:

Conidia Asexual spores Formed off of hyphae Common Airborne

Blastoconidia

“Buds” on yeasts (asexual budding daughter yeast cells)

Arthroconidia Asexual spores formed by a “joint.”

Spherules and Endospores (Coccidioides) Spores inside the spherules in tissues

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Spore Types: Conidia: Asexual spores, formed off of hyphae, common, airborne

Blastoconidia: “Buds” on yeasts (asexual budding daughter yeast cells)

Arthroconidia: Asexual spores formed by a “joint”

Spherules and Endospores (Coccidioides): Spores inside the spherules in tissues

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Diagnosis Table III-1. Microscopic Methods/Special Fungal Stains Preparation Fungal color NotesKOH wet mount (KOH degrades human tissues releasing hyphae and yeasts)

Colorless (hyaline) refractive green or light olive to brown (dematiaceous) fungal elements

Heat gently; let set 10 minutes; dissolves human cells

PAS Hot pink

Silver stain Old rose gray to black

Calcofluor White

(Can be done on wet mounts.)

Bright blue-white on black

Scrapings or sections, fluorescent microscope needed

India ink wet mount of CSF sediment

Colorless cells with halos (capsule) on a black particulate background (Cryptococcus neoformans)

Only "rules in." Insensitive; misses 50%. [Figure III-10. India ink mount of Crypto 5/8"]

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Diagnosis Table III-1. Microscopic Methods/Special Fungal Stains Preparation Fungal color NotesKOH wet mount

(KOH degrades human tissues releasing hyphae and yeasts)



PAS Hot pinkSilver stain Old rose gray to blackCalcofluor White (Can be done on wet mounts.)






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PAS Hot pinkSilver stain Old rose gray to black

Calcofluor White







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PAS Hot pinkSilver stain Old rose gray to black

Calcofluor White







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Culture: Special fungal media: Inhibitory mold agar modification of Sabouraud's with antibiotics

Sabouraud’s Blood agar Both of the above with antibiotics

Serology: Antibody screen, complement fixation, etc. Fungal Antigen Detection: (CSF, serum); Cryptococcal capsular polysaccharide detection by latex particle agglutination (LPA) or counter immuno electrophoresis Skin Tests: Most useful for epidemiology or demonstration of anergy to an agent you know patient is infected with (grave prognosis); Otherwise, like tuberculosis, a skin test only indicates exposure to the agent.

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Sporothrix schenckii Dimorphic Fungus Environmental form: On plant material, worldwide as hyphae with rosettes and sleeves of conidia Traumatic implantation (rose or plum tree thorns, wire/sphagnum moss) Tissue form: cigar-shaped yeast in tissue Sporotrichosis (rose gardener’s disease): subcutaneous or lymphocutaneous lesions Treatment: Itraconazole or potassium iodide in milk (no antifungal activity) Pulmonary (acute or chronic) sporotrichosis: Urban alcoholics, particularly homeless

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Deep Fungal Infections Histoplasma Coccidioides Blastomyces

All three cause: Acute pulmonary (asymptomatic or self-resolving

in about 95% of the cases) Chronic pulmonary, or

Disseminated infections

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Histoplasma capsulatum Dimorphic fungus Environmental form: Hyphae with microconidia and tuberculate macroconidia Endemic region: Eastern Great Lakes, Ohio, Mississippi, and Missouri River beds Found in soil (dust) enriched with bird or bat feces Spelunking (cave exploring), cleaning chicken coops, or bulldozing starling roosts Tissue form: Small intracellular yeasts with narrow neck on bud; no capsule Facultative intracellular parasite found in reticuloendothelial (RES) cells

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Histoplasma capsulatum Fungus flu (a pneumonia) Asymptomatic or acute (but self-resolving) pneumonia with flu-like symptomatology Hepatosplenomegaly may be present even in acute pulmonary infections (facultative intracellular-RES) Very common in summer in endemic areas: kids or newcomers (80% of adults are skin test positive in some areas) Lesions have a tendency to calcify as they heal Relapse potential increases with T cell immunosuppression Disseminated infections: Mucocutaneous lesions are common; also common in AIDS patients in endemic area Treat with amphotericin B

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Histoplasma capsulatum Fungus flu (a pneumonia)

Asymptomatic or acute (but self-resolving) pneumonia with flu-like symptomatology Hepatosplenomegaly may be present even in acute pulmonary infections (facultative intracellular-RES) Very common in summer in endemic areas: kids or newcomers (80% of adults are skin test positive in some areas) Lesions have a tendency to calcify as they heal Relapse potential increases with T cell immunosuppression Disseminated infections: Mucocutaneous lesions are common; also common in AIDS patients in endemic area

Treat with amphotericin B

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Coccidioides immitis Dimorphic Fungus Environmental form: Hyphae breaking up into arthroconidia found in desert sand Endemic region: Southwestern United States, Southern California (especially San Joaquin Valley), Arizona, New Mexico, Texas, Nevada Arthroconidia are inhaled, round up, and enlarged becoming spherules inside which the cytoplasm wall off, forming endospores within which the endospore develop Tissue form: Spherules with endospores

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Coccidioides immitis Valley Fever (asymptomatic to self-resolving pneumonia)

Desert bumps (erythema nodosum) and arthritis are generally good prognostic signs Very common in endemic region Pulmonary lesions have a tendency to calcify as they heal Systemic infections are a problem in AIDS and immunocompromised patients in endemic region Cocci has a tendency to disseminate in 3rd trimester of pregnancy

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Blastomyces dermatitidis Dimorphic Fungus Environmental form: Hyphae with nondescript conidia Association not definitively known, appears to be associated with rotting wood such as beaver dams Endemic region: Upper Great Lakes, Ohio, Mississippi River beds plus the southeastern seaboard of the U.S. and northern Minnesota into Canada Tissue form: Broad-based budding yeasts and a double refractile cell wall

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Blastomyces dermatitidis Blastomycosis

Acute and chronic pulmonary disease Considered less likely to self-resolve than Histoplasma or Coccidioides. So many physicians will treat even acute infections with ketoconazole. Disseminated disease

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Aspergillus fumigatus Monomorphic filamentous fungus: Dichotomously branching, Generally acute angles, Septate One of our major recyclers: compost pits, moldy

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Aspergillus fumigatus

Diseases/Predisposing Conditions Allergic bronchopulmonary aspergillosis/asthma, allergies (growing in mucous plugs in the lung but not penetrating the lung tissue) Fungus ball: free in preformed lung cavities (surgical removal to reduce coughing, which may induce pulmonary hemorrhage) Invasive aspergillosis/severe neutropenia, CGD, CF, burns

Invades tissues causing infarcts and hemorrhage Nasal colonization pneumonia or meningitis Cellulitis/in burn patients; may also disseminate

Treatment: Depends on severity of disease and underlying conditions - Itraconazole or Amphotericin B

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Invades tissues causing infarcts and hemorrhage

Nasal colonization pneumonia or meningitis

Cellulitis/in burn patients; may also disseminate


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Invades tissues causing infarcts and hemorrhage

Nasal colonization pneumonia or meningitis

Cellulitis/in burn patients; may also disseminate


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Candida albicans (And Other Species of Candida) Yeast endogenous to our mucous membrane normal flora C. albicans yeasts form germ tubes at 37°C in serum Form pseudohyphae and true hyphae when it invades tissues (nonpathogenic Candida do not)

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Candida albicans (And Other Species of Candida)

Diagnosis

KOH: pseudohyphae, true hyphae, budding yeasts Septicemia: Culture lab identification: biochemical tests/formation of germ tubes

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Diagnosis


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Diagnosis


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of 66Candida albicans (And Other Species of Candida) Diseases/Predisposing Conditions

Perlèche - crevices of mouth: malnutrition Oral thrush: prematurity, antibiotic use, immunocompromised (IC) host, AIDS Esophagitis: antibiotic use, IC host, AIDS Gastritis: antibiotic use, IC host, AIDS Septicemia (with endophthalmitis and macronodular skin lesions): immunocompromised, cancer and intravenous (IV) patients Endocarditis (with transient septicemias):IV drug abusers Cutaneous infections: obesity and infants; patients with rubber gloves Yeast vaginitis: particularly a problem in diabetic women Chronic mucocutaneous candidiasis: endocrine defects; anergy to Candida

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Candida albicans (And Other Species of Candida) Diseases/Predisposing Conditions


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Candida albicans (And Other Species of Candida) Treatment

Topical imidazoles or oral imidazoles; nystatin disseminated: Amphotericin B or Fluconazole

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Cryptococcus neoformans Encapsulated Yeast (Monomorphic) Environmental Source: Soil enriched with pigeon droppings Meningitis: Hodgkin’s, AIDS (the dominant meningitis) Acute pulmonary (usually asymptomatic): pigeon breeders

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Cryptococcus neoformans Diagnosis of Meningitis: CSF

Detect capsular antigen in CSF (by latex particle agglutination, or counter immunoelectrophoresis) India ink mount (misses 50%) of CSF sediment to find budding yeasts with capsular “halos” Cultures (urease positive yeast) Treatment: AMB+5FC until afebrile and culture negative, then fluconazole

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Cryptococcus neoformans Diagnosis of Meningitis: CSF

Detect capsular antigen in CSF (by latex particle agglutination, or counter immunoelectrophoresis) India ink mount (misses 50%) of CSF sediment to find budding yeasts with capsular “halos” Cultures (urease positive yeast) Treatment: AMB+5FC until afebrile and culture

negative, then fluconazole

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Mucor, Rhizopus, Absidia (Zygomycophyta) Nonseptate filamentous fungi Environmental Source: Soil, sporangiospores are inhaled Disease characterized by paranasal swelling, necrotic tissues, hemorrhagic exudates from nose and eyes, and mental lethargy Occurs in ketoacidotic diabetic patients and leukemic patients These fungi penetrate without respect to anatomical barriers, progressing rapidly from sinuses into the brain tissue

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Pneumocystis carinii Fungus (based on molecular techniques like ribotyping) Obligate extracellular parasite Silver stained cysts in tissues Interstitial pneumonia

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Pneumocystis carinii Pneumonia in AIDS patients even with prophylaxis (mean CD4+/mm3 of 26) malnourished babies, premature neonates, and some other IC adults and kids Symptoms: fever, cough, shortness of breath; sputum nonproductive except in smokers Pneumocystosis attaches to and kills Type I pneumocytes causing excess replication of Type II pneumocytes and damage to alveolar epithelium. Serum leaks into alveoli producing an exudate with a foamy or honeycomb appearance on H & E stain. X-ray: Patchy infiltrative (ground glass appearance), the lower lobe periphery may be spared Diagnosis: Silver-staining cysts in bronchial alveolar lavage fluids or biopsy Treatment: Trimethoprim/sulfamethoxazole

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