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Micro > chronic necrotizing pneumonia: fungal > Flashcards

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

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2
Q

fungi disting. based on

A

morphology of spores and hyphal elements

bac: stain, cell/colony morph., biochem rxns

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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

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4
Q

yeast

A

round-oval elongated single cell

reprod. by budding, form moist or mucoid colonies (resem. G+ cocci)

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5
Q

pseudohyphae (yeast)

A

buds remain attached to mom (candida), elongate, lack parallel sides and pinching septa

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6
Q

true hyphae

A

parallel sides, true horiz. septa, can prod. terminal, thick walled chlamydoconidia

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7
Q

candida albicans (not other spp.) produces a

A

germ tube in human serum @ 37 degrees C

ddx for c. albicans

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8
Q

yeast cells can convert

A

into hyphe/pseudohyphae and back again, dimorphic, but not thermally dimorphic

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9
Q

thermally dimorphic fungi

A

yeast OR spherules/endospores (parasitic) in host/in vitro @ 37 C

mold (saprobic) in environ. @ 21-24 C

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10
Q

therm. dimorph fungi orgs

A

histoplasma capsulatum
blastomyces dermatitidis
coccidioides immitis, c. posadasii
sporothrix schenckii

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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)

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12
Q

microconidia-prod. spp.

A

histoplasma capsulatum
blastomyces dermatitidis
aspergillus spp.
murcormycoses

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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

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14
Q

sporangiospores

A

spores w. in sac-like structures (sporangia)

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15
Q

sporangia prod. spp

A

coccidiodes immitis and c. posadasii: spherules**

PCP (pneumocystis jiroveci)-cysts w. endospores (8)

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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*
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17
Q

yeast produce spores called

A

blastospores: buds

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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)

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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)

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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

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21
Q

host immune system determines fungal pathogen infections, esp.

A 
T cell deficiencies
phagocytic cells (PMNs, macros)
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22
Q

T cell opportunistic fungi

A 
histoplasma capsulatum
blastomyces dermatitidis
coccidioides immitis and posadasii
cryptococcus neoformans
candida albicans and other spa.
pneumocystis jiroveci
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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)

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24
Q

phagocytic cell opportunists

A

aspergillus
zygomycetes class (mucormycosis)
@ risk:
prol. neutropenia (depressed PMNs

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25
Q

normal functioning phago cells

A

macros destry conidia

PMS destroy hyphae

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26
Q

causes of iron overload

A

kidney dialysis
unreg. DM: DKA inhib. iron bind to transferrin: elev. Fe in serum
hemochromatosis

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27
Q

the systemic mycoses (histoplasma apsulatum, blastomyces dermatitidis, coccidioides immitis and posadasii)

A

primarily pulm. pathogens
most common syst. fungal inf. in immunocompetent and immunocompromised hosts in NA
eukaryotic, thermally dimorphic

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28
Q

H. capsulatum and B. dermatitis produce this in soil (25 C) that are infectious to humans

A

microconidia (spores)–>yeast in humans: parasitic form (37 C)

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29
Q

C. immitis and C. posadasii produce this in soil (25 C) that are infectious to humans

A

arthrospores (resistant, barrel-shaped)–>spherule and endospores: parasitic form (37C)

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30
Q

systemic mycoses: transmitted person to person?

A

NO, via inhalation of aerosolized microconidia/arthrospores (not via resp. droplets)
(target is LRT)

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31
Q

histoplasma capsulatum (histoplasmosis, Darling’s disease, spelunker’s)

A

Ohio-Miss. river valley, guano

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32
Q

blastomyces dermatitidis (blastomycosis, Chicago disease)

A

soil near lakes, rivers of Missouri, Arkansas, St. Lawrence, overlaps w. histo but larger

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33
Q

coccidoides immitis and c. posadasii (coccidioidomycosis, desert rheumatism, valley fever, san joaquin valley fever)

A

American SW, Latin America

C. immitis: San Joaquin Valley

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34
Q

syst. mycoses patho

A

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.

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35
Q

syst. mycoses patho: host response to inf

A

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

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36
Q

syst. mycoses s/s (sev. options)

A
  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)
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37
Q

progressive disseminated targets of histoplasmosis

A

liver, spleen, adrenals

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38
Q

progressive disseminated targets of blastomycosis

A

skin, soft tissue, bone (osteolytic), GU tract

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39
Q

progressive disseminated targets of coccidioidomycosis

A

skin, soft tissue (rashes), bones (osteolytic, skel. pain), joint/synovium, CNS (meningitis)

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40
Q

systemic mycosal infections CXR

A

heal by fibrosis–>necrotic “coin-like” lesions (like TB/neoplasm) *esp. histoplasmosis

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41
Q

systemic mycosis s/s in sev. immsuppr. pts

A

fever, w.l., night sweats, pulm. sympts (cough, dyspnea), anemia in many pts, loc. or gen. lymphadenopathy, hepatosplenomegaly, skin/colon ulcers

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42
Q

syst. mycoses dx: stain/Cx

A

KOH-sample stain shows parasitic form (yeast or spherule)
Cx: variable growth, alert lab (esp. C. immitis, C. posadasii- dangerous!)
DNA probs/exoantigen tests

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43
Q

syst. mycoses dx: serology?

A

Yes, for b, h, c

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44
Q

syst. mycoses dx: DTH skin testing

A

histoplasmin (mycelial Ag) : epi studies of histoplasmosis

spheruline: dx/px of coccidioidomycosis

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45
Q

syst. mycoses CXR:

A 
variable; 
coin-like lesions/nodular masses
diffuse bilateral alveolar infiltrates
consolidation
combos of above
46
Q

syst. mycoses tx

A

Amphotericin B lipid formulation- may be prolonged

47
Q

histoplasma capsulatum epi

A

wood w/ bird poop

48
Q

histo cap patho

A

asymptomatic, may observed calcified tubercle-like lesions on XR: liver, spleen, adrenals, lungs

49
Q

histo cap: progressive disseminated disease (Darling’s)

A

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
Q

histo cap dx:

A 
like TB (infiltr/consol. on XR)
rounded-oval yeast forms in macros
51
Q

histo cap dx: serology

A

-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
Q

histo cap tx

A

Amphotericin B, oral itraconazole after

53
Q

blastomyces dermatitidis epi

A

also dis. in dogs

54
Q

blasto derm patho

A 
chronic necr. pneumo + coin-like lesions
extrapulm manifests: 
*skin lesions-like SCC*
bone lesions
GU- less common, prostate, epidid.
55
Q

blasto derm dx:

A
  • BROAD-BASED, budding yeast form w/ v. THICK WALLS*

- ELISA (screen), immunodiffustion (confirm)

56
Q

blasto derm tx:

A

Amphotericin B, oral itraconazol after

57
Q

coccidioides immitis and posadasii virulence factor

A

estrogen-binding proteins (progesterone, testosterone, 17B-estradiol)
inc. steroid hormone levels–>stim. growth and maturation of spherules

58
Q

c. immi and posa epi

A

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
Q

c. immi and posa patho

A

60% asymptomatic, (DTH test + to spherulin)

40% inf.: symptomatic 2 wks (10-16d)

60
Q

c. immin and posa s/s

A

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
Q

desert rheumatism: 2 triads

c. immi and posa

A

fever, erythema nodosom, arthralgias

conjunctivitis, erythema nodosum, arthralgias

62
Q

c. immi and posa pathognomonic dx

A

spherules: 5-40 um and/or endospores in tissue

63
Q

c. immi and posa serology dx

A

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
Q

c. immi/posa most likely if

A

+ 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
Q

c. immi/posa tx

A

amphotericin B, then oral itraconazol

66
Q

aspergillosis and mucormycosis/zygomycetes epi

A

both: ubiquitous distribution (geography), POE is RT (inhalation of microconidia)
(inhale sev. 100 A. fumigatus conidia/day)

67
Q

asperg. patho

A

allergic bronchopulm. aspergillosis (ABPA): in bronchial asthmatic pt
aspergilloma (“fungus ball”) lung parenchymal displacing mass
invasive aspergillosis (IA)

68
Q

asperg and mucor dx (both)

A

clin. features depend on organ, XR, Cx/microscopic evidence

69
Q

asperg dx

A

resence of aspergillus galactomannan (GM) in BAL specimen or serum
halo sign by lung CT scan

70
Q

asperg and mucor tx

A

voriconazole (broad-spec triazole) followed by amphotericin B

71
Q

asperg and mucor ppx

A

posaconazole (not fluconazole, itraconazole)

72
Q

aspergillosis: dimorphic fungus?

A

no

73
Q

aspergillosis spp.

A

a. fumigatus (most common), a. flavus, a. niger

74
Q

asperg cell morph

A

non-pigmented, harry septate hyphae (“soldiers marching in a row”), acute angle branching (45-90 degrees)

75
Q

asperg epi

A

ubiquitous geo, POE RT, inhale lots a. fumigatus conidia/day

76
Q

asperg risk factors

A

(gen ones) +
lung structural abnormalities
over-exuberant IR (hypersens, atopy?) in allergic asperg.
severely immcompromised

77
Q

asperg: syndromes involving mycelia growth in body, req. tx

A

ABPA: allergic bronchopulmonary aspergillosis
aspergilloma
IA: invasive aspergillosis

78
Q

ABPA

A

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
Q

ABPA clin manifests

A

worsening bronch. asthma (brown mucus plugs in prod. cough + wheezing), transient pulm. infilt.–> fatal lung destruction

80
Q

ABPA: Loeffler’s syndrome

A

fever, cough, *urticaria, wheezing, inter. infilt. on CXR, sputum + eosinophilia (>500/mm3) + Charcot-Leyden crystals (deg. eosinophil granules), peripheral eosino. w. CBC

81
Q

ABPA: 5 major definitive dx

A

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
Q

aspergilloma

A

“fungus ball” of fungal hyphae

  • displaces lung parenchyma
  • in 10-15% of cavities from lung dis (TB, sarcoid)
  • chronically obstr. paranasal sinuses
83
Q

aspergilloma patho

A
  • 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
Q

aspergilloma symps

A

hemoptysis, bronchiectases in late disease

85
Q

aspergilloma dx

A

CATscan: spherical mass surrounded by radioluscent crescent
bronchioscope: fungal ball

86
Q

invasive aspergillosis (IA)

A

acute or chronic pulmonary IA* most

  • other: tracheobronchitis, obstructive dis. (AIDS), acute/chronic invasive rhinosinusitis
  • dissem. sites: brain, skin, eyes
87
Q

IA risk factors

A 
*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
Q

IA patho

A

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
Q

IA presentation in neutropenic pt

A

persistant fever, fails to respond to br. spec abx
+/- cough, min sputum prod.
hemoptysis is uncommon

90
Q

aspergillosis dx: imaging

A

(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
Q

aspergillosis dx: Cx

A

narrow, septate hyphae w. acute angle (45-90) branching, in tissue

92
Q

aspergillosis dx: serum

A 
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
Q

aspergillosis tx

A

voriconazol (b-spec triazole) then amphotericin B

  • *survival rates POOR** (>80% mortality w. CMI suppression)
    ppx: posaconazole
94
Q

mucormycosis/zygomycosis: dimorphic?

A

NO

95
Q

mucormycosis/zygomycosis orgs

A

absidia, mucor, rhizomucor, rhizopus

96
Q

mucor cell morph

A

variable width (6-25 um), broad, ribbon-like
thin walled
infreq. septat or aseptate hyphae
irregular branching (includes wide angle 90)

97
Q

mucor patho

A

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
Q

mucor manifests

A

persistant fever, rap. prog. pneumo w. hemoptysis, pleuritic CP

99
Q

mucor dx

A

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
Q

mucor tx

A

voriconazole then amphotericin B

no ppx

101
Q

5-fluorocytosine (5-Fc)

A

nucleoside analog

interferes w. DNA and RNA syn/func

102
Q

griseofulvin

A

mitosis inhibitor

inhibition of fungal cell mitosis at metaphase by interaction w. polymerized microtubules

103
Q

echinocaandins, pneumocandins, caspofungin

A

inhib. cell wall syn. by inhib. syn. of 1,3-B-D-glucan in fungal cell walls

104
Q

amphotericin B-lipid formulations

A

polyene antibiotics

interaction w. ergosterol, formation of aqueous channels, inc. mem. perm to univalent cations and –>cell death

105
Q

ketoconazole

A

imidazole/azole

causes ergosterol depletion and accum. of aberrant and toxic sterols in cell mem

106
Q

flucanozole

A

imidazole/azole

causes ergosterol depletion and accum. of aberrant and toxic sterols in cell mem

107
Q

itraconazole

A

imidazole/azole

causes ergosterol depletion and accum. of aberrant and toxic sterols in cell mem

108
Q

voriconazole

A

imidazole/azole

causes ergosterol depletion and accum. of aberrant and toxic sterols in cell mem

109
Q

amorolfine

A

morpholine

inhib. sterol reductase and isomerase

110
Q

terbinafine

A

allylamines/thiocarbamates

causes ergosterol depletion and accum. of aberrant and toxic sterols in the mem

Micro (61 decks)

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