chronic necrotizing pneumonia: fungal Flashcards
1
Q
fungi characteristics
A
more “human-like” (EUK) so tx is v. toxic (amphoteracin B)
heterotrophs, absorb nutrients, parasitic
obligate aerobes, EXCEPT YEAST: facult. anaerobe
cell wall: polysacchs(glucan, chitin) and glycoproteins
cell mem: ergosterol, other sterols (site of drug axn)
some encapsulated: cryptococcus neoformans
2
Q
fungi disting. based on
A
morphology of spores and hyphal elements
bac: stain, cell/colony morph., biochem rxns
3
Q
2 basic fungi growth forms
A
molds/mycelial (saprobic) growth:
spores germ.–>hyphae (branching or unbranched filaments) +/- septa, (hyphal mass: mycelial)
sexual and asexual spores
yeast OR spherules w. endospores
4
Q
yeast
A
round-oval elongated single cell
reprod. by budding, form moist or mucoid colonies (resem. G+ cocci)
5
Q
pseudohyphae (yeast)
A
buds remain attached to mom (candida), elongate, lack parallel sides and pinching septa
6
Q
true hyphae
A
parallel sides, true horiz. septa, can prod. terminal, thick walled chlamydoconidia
7
Q
candida albicans (not other spp.) produces a
A
germ tube in human serum @ 37 degrees C
ddx for c. albicans
8
Q
yeast cells can convert
A
into hyphe/pseudohyphae and back again, dimorphic, but not thermally dimorphic
9
Q
thermally dimorphic fungi
A
yeast OR spherules/endospores (parasitic) in host/in vitro @ 37 C
mold (saprobic) in environ. @ 21-24 C
10
Q
therm. dimorph fungi orgs
A
histoplasma capsulatum
blastomyces dermatitidis
coccidioides immitis, c. posadasii
sporothrix schenckii
11
Q
molds can produce spores called..
A
conidia: “naked” spores, unenclosed
macroconidia: large, CANNOT cause RT disease
microconidia: small, can get into alveoli, can cause RT inf. (21-24 C: environ./in vitro)
12
Q
microconidia-prod. spp.
A
histoplasma capsulatum
blastomyces dermatitidis
aspergillus spp.
murcormycoses
13
Q
arthroconidia (arthrospores)
A
(mold-produced)
thick-walled, fragments of hyphal cells
can cause RT inf.
coccidioides immitis and c. posadasii in environ/in vitro @ 21-24 C
14
Q
sporangiospores
A
spores w. in sac-like structures (sporangia)
15
Q
sporangia prod. spp
A
coccidiodes immitis and c. posadasii: spherules**
PCP (pneumocystis jiroveci)-cysts w. endospores (8)
16
Q
c. immitis and c. posadasii produce sporangiospores…
A
spherules (sporangia) bearing endospores (sporangiospores)
- *spherules is pathognomonic for coccidioidomycoses**
- rupture–>rel. endospores, can dev. into spherule
- neither is infectious*
17
Q
yeast produce spores called
A
blastospores: buds
18
Q
systemic mycoses (mycoses=fungal infections)
A
most serious, break down int. orgs, viscera (enter via RT, skin break)
orgs:
blastomyces dermatitidis
coccidioides immitis and c. posadasii
histoplasma capsulatum
cryptococcus neoformans var. grubii (CNS)
19
Q
opportunistic mycoses
A
human NF or environ. orgs, cause lesions on mucus mem. or in skin, RT, CNS
(@ risk: br-sp abx tx, IC)
orgs:
aspergillus
cryptococcus neoformans var. grubii
candida spp.most important
zygomycetes class: absidia, mucor, rhizomucor, rhizopus (mucormycosis)
20
Q
fungal pneumo CANNOT be dx by
A
routine sputum Cx
s/s (no unique)
*does NOT respond to antibiotics
-pay attn to hx, PE, epidemiology
21
Q
host immune system determines fungal pathogen infections, esp.
A
T cell deficiencies phagocytic cells (PMNs, macros)
22
Q
T cell opportunistic fungi
A
histoplasma capsulatum blastomyces dermatitidis coccidioides immitis and posadasii cryptococcus neoformans candida albicans and other spa. pneumocystis jiroveci
23
Q
what is required to control fungal inf. and/or disease
A
CMI: non-immune ppl can be infected, also those w. imp. T cell function: HIV+, glucocorticosteroid/immsupp tx (SOT)
24
Q
phagocytic cell opportunists
A
aspergillus
zygomycetes class (mucormycosis)
@ risk:
prol. neutropenia (depressed PMNs
25
normal functioning phago cells
macros destry conidia
| PMS destroy hyphae
26
causes of iron overload
kidney dialysis
unreg. DM: DKA inhib. iron bind to transferrin: elev. Fe in serum
hemochromatosis
27
the systemic mycoses (histoplasma apsulatum, blastomyces dermatitidis, coccidioides immitis and posadasii)
primarily pulm. pathogens
most common syst. fungal inf. in immunocompetent and immunocompromised hosts in NA
eukaryotic, thermally dimorphic
28
H. capsulatum and B. dermatitis produce this in soil (25 C) that are infectious to humans
microconidia (spores)-->yeast in humans: parasitic form (37 C)
29
C. immitis and C. posadasii produce this in soil (25 C) that are infectious to humans
arthrospores (resistant, barrel-shaped)-->spherule and endospores: parasitic form (37C)
30
systemic mycoses: transmitted person to person?
NO, via inhalation of aerosolized microconidia/arthrospores (not via resp. droplets)
(target is LRT)
31
histoplasma capsulatum (histoplasmosis, Darling's disease, spelunker's)
Ohio-Miss. river valley, guano
32
blastomyces dermatitidis (blastomycosis, Chicago disease)
soil near lakes, rivers of Missouri, Arkansas, St. Lawrence, overlaps w. histo but larger
33
coccidoides immitis and c. posadasii (coccidioidomycosis, desert rheumatism, valley fever, san joaquin valley fever)
American SW, Latin America
| C. immitis: San Joaquin Valley
34
syst. mycoses patho
sev. immsuppr pts @ risk
* asymptomatic more common
- micro/arthr are phago by non-act. macros
* only histo grows IC
- ->all may dissem. via blood-->extrapulm. inf.
35
syst. mycoses patho: host response to inf
sp. CD4+ T cells required for control of inf., need activated macros (transplant, HIV pts @ risk)
effective CMI forms tubercle-like lesion where repo. happens-->calcify
incubation period: 1-3 wks
36
syst. mycoses s/s (sev. options)
1. flu-like/bronchitis: fever, malaise, dry, non prod. cough
2. flu-like w. anything from atypical pneumo-->chronic granulomatous disease in lungs (indist. from pulmonary tb) and cavitary lesions (+/- night sweats, anorexia/W.L., dry non prod. cough or prod. +/- hemoptysis, CP (p/np), SOB, dyspnea
3. *progressive dissem./systemic disease*: EITHER
- gen. systemic inf/dis
- extrapulm. inf. of sp. orgs. or tissues +/- pulm. involvement (each organ has sp. targets)
37
progressive disseminated targets of histoplasmosis
liver, spleen, adrenals
38
progressive disseminated targets of blastomycosis
skin, soft tissue, bone (osteolytic), GU tract
39
progressive disseminated targets of coccidioidomycosis
skin, soft tissue (rashes), bones (osteolytic, skel. pain), joint/synovium, CNS (meningitis)
40
systemic mycosal infections CXR
heal by fibrosis-->necrotic "coin-like" lesions (like TB/neoplasm) *esp. histoplasmosis
41
systemic mycosis s/s in sev. immsuppr. pts
fever, w.l., night sweats, pulm. sympts (cough, dyspnea), anemia in many pts, loc. or gen. lymphadenopathy, hepatosplenomegaly, skin/colon ulcers
42
syst. mycoses dx: stain/Cx
KOH-sample stain shows parasitic form (yeast or spherule)
Cx: variable growth, alert lab (esp. C. immitis, C. posadasii- dangerous!)
DNA probs/exoantigen tests
43
syst. mycoses dx: serology?
Yes, for b, h, c
44
syst. mycoses dx: DTH skin testing
histoplasmin (mycelial Ag) : epi studies of histoplasmosis
| spheruline: dx/px of coccidioidomycosis
45
syst. mycoses CXR:
```
variable;
coin-like lesions/nodular masses
diffuse bilateral alveolar infiltrates
consolidation
combos of above
```
46
syst. mycoses tx
Amphotericin B lipid formulation- may be prolonged
47
histoplasma capsulatum epi
wood w/ bird poop
48
histo cap patho
asymptomatic, may observed calcified tubercle-like lesions on XR: liver, spleen, adrenals, lungs
49
histo cap: progressive disseminated disease (Darling's)
in adults: like military TB; lesions in liver, spleen, adrenals-->may result in Addison's
in infant: persist. fever, hepatosplenomegaly, death in 6 wks if unto
*charac. by massive parasitism of macros*
50
histo cap dx:
```
like TB (infiltr/consol. on XR)
rounded-oval yeast forms in macros
```
51
histo cap dx: serology
-complement fixation (mycelial Ag and whole yeast cell Ags (histolyn)
-immunodiffusion test:
H Ag+: active histo, primary dis.
M Ag+: acute or chronic dis.
-RIA (polysac. Ag in urine/serum), ELISA (Ab to histo Ag 69-70kDa in serum)
52
histo cap tx
Amphotericin B, oral itraconazole after
53
blastomyces dermatitidis epi
also dis. in dogs
54
blasto derm patho
```
chronic necr. pneumo + coin-like lesions
extrapulm manifests:
*skin lesions-like SCC*
bone lesions
GU- less common, prostate, epidid.
```
55
blasto derm dx:
* BROAD-BASED, budding yeast form w/ v. THICK WALLS*
| - ELISA (screen), immunodiffustion (confirm)
56
blasto derm tx:
Amphotericin B, oral itraconazol after
57
coccidioides immitis and posadasii virulence factor
estrogen-binding proteins (progesterone, testosterone, 17B-estradiol)
inc. steroid hormone levels-->stim. growth and maturation of spherules
58
c. immi and posa epi
SW US (immitis), Latin America
rains-germinate in soil-mycelia grow-form arthroconidia-dust stirred up-epidemics
*dissem: males, preggos (3rd trimester), immsuppr, minorities?
*SUMMER!*
59
c. immi and posa patho
60% asymptomatic, (DTH test + to spherulin)
| 40% inf.: symptomatic 2 wks (10-16d)
60
c. immin and posa s/s
see earlier for gen. manifest.
cutaneous: macpap rash (esp. kiddos), erythema nodosum/multiform (white women, good px)
-traids
most self-limiting, not all, dissemination is rare (0.5%) but insidious and fulminant
61
desert rheumatism: 2 triads
| c. immi and posa
fever, erythema nodosom, arthralgias
| conjunctivitis, erythema nodosum, arthralgias
62
c. immi and posa pathognomonic dx
*spherules: 5-40 um and/or endospores in tissue*
63
c. immi and posa serology dx
IgM: + 1st mo, neg by 2 mos (prim. inf)
| IgG titers: +2-3 wks-8mos, dx and px (high-disseminated, drop w/ succ. tx)
64
c. immi/posa most likely if
+ spherulin rxn (w.in 3 wks, good px)
s/s consistent
resident/travel to endemic area (SW, LA)
(w. disseminated, may be DTH -: high relapse rates, converts to + w/ succ. tx)
65
c. immi/posa tx
amphotericin B, then oral itraconazol
66
aspergillosis and mucormycosis/zygomycetes epi
both: ubiquitous distribution (geography), POE is RT (inhalation of microconidia)
(inhale sev. 100 A. fumigatus conidia/day)
67
asperg. patho
allergic bronchopulm. aspergillosis (ABPA): in bronchial asthmatic pt
aspergilloma ("fungus ball") lung parenchymal displacing mass
invasive aspergillosis (IA)
68
asperg and mucor dx (both)
clin. features depend on organ, XR, Cx/microscopic evidence
69
asperg dx
resence of aspergillus galactomannan (GM) in BAL specimen or serum
halo sign by lung CT scan
70
asperg and mucor tx
voriconazole (broad-spec triazole) followed by amphotericin B
71
asperg and mucor ppx
posaconazole (not fluconazole, itraconazole)
72
aspergillosis: dimorphic fungus?
no
73
aspergillosis spp.
a. fumigatus (most common), a. flavus, a. niger
74
asperg cell morph
non-pigmented, harry septate hyphae ("soldiers marching in a row"), acute angle branching (45-90 degrees)
75
asperg epi
ubiquitous geo, POE RT, inhale lots a. fumigatus conidia/day
76
asperg risk factors
(gen ones) +
lung structural abnormalities
over-exuberant IR (hypersens, atopy?) in allergic asperg.
severely immcompromised
77
asperg: syndromes involving mycelia growth in body, req. tx
ABPA: allergic bronchopulmonary aspergillosis
aspergilloma
IA: invasive aspergillosis
78
ABPA
most sev. allergic pulm comp caused by aspergillus spp.
in some pts w. atopic asthma (1-2%) or CF (7-35%)
*immunopathology* hurts host more than fungal growth
79
ABPA clin manifests
worsening bronch. asthma (brown mucus plugs in prod. cough + wheezing), transient pulm. infilt.--> fatal lung destruction
80
ABPA: Loeffler's syndrome
fever, cough, *urticaria, wheezing, inter. infilt. on CXR, *sputum + eosinophilia (>500/mm3) + Charcot-Leyden crystals (deg. eosinophil granules), peripheral eosino. w. CBC*
81
ABPA: 5 major definitive dx
asthma hx
immediate (15mm+/-5mm) skin reactivity to A. fumigatus Ag extract
elevated serum levels IgM, IgG, IgE against A. fumigates
elevated total IgE serum levels (>1 ug/mL)
central (proximal) bronchiectasis
82
aspergilloma
"fungus ball" of fungal hyphae
- displaces lung parenchyma
- in 10-15% of cavities from lung dis (TB, sarcoid)
- chronically obstr. paranasal sinuses
83
aspergilloma patho
- spheroid mass of hyphae in proteinaceous matrix w. sporulating structures @ periphery
- balls external to cavity lining (i.e. airway)
- as hyphae grow, rel. enzymes-->destroy human tissue and break down macromol (protein, aas)-->disrupt BVs in cavity wall/bronchial supply-->1 or both: massive internal bleeding +/- hemoptysis (bleed in airway) (either can be fatal)
84
aspergilloma symps
hemoptysis, bronchiectases in late disease
85
aspergilloma dx
CATscan: spherical mass surrounded by radioluscent crescent
bronchioscope: fungal ball
86
invasive aspergillosis (IA)
acute or chronic pulmonary IA* most
- other: tracheobronchitis, obstructive dis. (AIDS), acute/chronic invasive rhinosinusitis
- dissem. sites: brain, skin, eyes
87
IA risk factors
```
*leading COD among*:
blood Ca: lymphoma, leukemia pts
sev. neutrophenic pts
tx w. cytotoxin for blood dis
BM transplant, SOT
kiddos w. chronic granulomatous disease
AIDS pts
```
88
IA patho
growth of fungus in lung tissue-->hemorrh. infection-->dissem via blood-->fungal hyphae grow in tissue (not ball in cavity)
(histo reveals 1/few short segments of larger hyphal elements)
89
IA presentation in neutropenic pt
persistant fever, fails to respond to br. spec abx
+/- cough, min sputum prod.
hemoptysis is uncommon
90
aspergillosis dx: imaging
(depends on organ location)
+ CT scan: large nodules w. "halo sign" (hazy, nonobstruc. ground glass attenuation)
-->invasion of vascu.-->hemorrhage (1st 10d), early sign
-air crescent sign-->later (IA), invasion-necrosis, host mounts an inflammatory resp
91
aspergillosis dx: Cx
narrow, septate hyphae w. acute angle (45-90) branching, in tissue
92
aspergillosis dx: serum
```
aspergillus galactomannan (GM) in BAL spec./serum, (not for SOTs) -detectable 5-8 days before s/s, correlates to fungal tissue burden, serial assays 2x/week + CT/Cx
-also: LAtest for GM, ELISA (using MAb sp. for 1-5-B-D-galactofuranose) side chains of GM
```
93
aspergillosis tx
voriconazol (b-spec triazole) then amphotericin B
* *survival rates POOR** (>80% mortality w. CMI suppression)
ppx: posaconazole
94
mucormycosis/zygomycosis: dimorphic?
NO
95
mucormycosis/zygomycosis orgs
absidia, mucor, rhizomucor, rhizopus
96
mucor cell morph
variable width (6-25 um), broad, ribbon-like
thin walled
infreq. septat or aseptate hyphae
irregular branching (includes wide angle 90)
97
mucor patho
typ: progressive and fatal w.in 2-3 wks
risks: abn. +/- LOW #s PMNs
infection from inhale. of spores into bronchioles and alveoli leading to prim. infarc/necrosis w. cavitation-->blood dissem to other orgs (brain)
98
mucor manifests
persistant fever, rap. prog. pneumo w. hemoptysis, pleuritic CP
99
mucor dx
need to make early!
ID ribbon-like, aseptate hyphae in tissue and Cx
*microscopy is most rapid dx*
"prominent infacrcts, angioinvasion and perineural invasion*: both aspergillus and mucormycoses
**Dx typically made on autopsy**
100
mucor tx
voriconazole then amphotericin B
| no ppx
101
5-fluorocytosine (5-Fc)
nucleoside analog
| interferes w. DNA and RNA syn/func
102
griseofulvin
mitosis inhibitor
| inhibition of fungal cell mitosis at metaphase by interaction w. polymerized microtubules
103
echinocaandins, pneumocandins, caspofungin
inhib. cell wall syn. by inhib. syn. of 1,3-B-D-glucan in fungal cell walls
104
amphotericin B-lipid formulations
polyene antibiotics
| interaction w. ergosterol, formation of aqueous channels, inc. mem. perm to univalent cations and -->cell death
105
ketoconazole
imidazole/azole
| causes ergosterol depletion and accum. of aberrant and toxic sterols in cell mem
106
flucanozole
imidazole/azole
| causes ergosterol depletion and accum. of aberrant and toxic sterols in cell mem
107
itraconazole
imidazole/azole
| causes ergosterol depletion and accum. of aberrant and toxic sterols in cell mem
108
voriconazole
imidazole/azole
| causes ergosterol depletion and accum. of aberrant and toxic sterols in cell mem
109
amorolfine
morpholine
| inhib. sterol reductase and isomerase
110
terbinafine
allylamines/thiocarbamates
| causes ergosterol depletion and accum. of aberrant and toxic sterols in the mem
