1. CPC #2: Shortness of breath, fevers, chills, and rigors Barbara J. Crain, M.D., Ph.D. October 6, 2009

2. External examination  Taut, thickened skin, face and extremities  Gangrene, fingertips and toes  Multiple blisters (1-15 cm), some disrupted, lower extremities

3. Heart  Epicardium: mild fibrosis, chronic inflammation  Myocardium: patchy subendocardial fibrosis

4. Kidney  Previous biopsy with arterio- and arteriolosclerosis, mild mesangial proliferation, and “full-house” immunostaining (IgG, IgA, IgM, C1q, C3)

5. Liver: zone 3 necrosis portal triad central vein

6. Trachea and bronchi  Multiple white plaques overlying hemorrhagic, necrotic mucosa

8. Aspergillus sp.  Dichotomous 45° branching  Septae  Culture: Aspergillus fumigatus

9. Lungs – gross examination  Combined weight 1100 gm (reference range 650- 1050 gm)  No pulmonary emboli  Small infarct in left upper lobe (2 x 1.5 cm)  Diffuse green discoloration in both lower lobes

10. Acute bronchopneumonia

11. Hemorrhage and necrosis

12. Rare hyaline membranes (diffuse alveolar damage)

13. Aspergillus  >185 species; ~ 20 cause human disease  Found in soil, associated with decaying plant material  May contaminate bread, potatoes  Most common: A. fumigatus, followed by A. flavus and A. niger  A. niger - Major component of mildew - Used commercially to produce citric acid, certain enzymes http://www.sciencedaily.com/images /2005/10/051015093046.jpg http://en.wikipedia.org/wiki/Aspergillus

14. Aspergilloma  “Fungus ball”  No tissue invasion  Usually pulmonary  Develop in previously formed cavities due to tuberculosis, sarcoidosis, bronchiectasis, etc. http://pathhsw5m54.ucsf.edu/case16/aspergilloma.html

15. Allergic bronchopulmonary aspergillosis (ABPA)  Hypersensitivity reaction  May mimic asthma or pneumonia  Risk factors: asthma, cystic fibrosis  Bronchocentric granulomas with numerous eosinophils and noninvasive Aspergillus organisms  Thick mucus plugs  Over time, bronchi become dilated, causing bronchiectasis

16. Invasive aspergillosis  Immunocompromised patients  High mortality rate  Route of entry generally lung  Hematogenous spread  Angioinvasion -Hemorrhages -Infarcts -Abscesses

17. Example: Aspergillosis in the CNS