Respiratory II. Infectious Disease Pathology. Respiratory System. Froberg. Katelyn Rogers. 11.08.09.
Interstitial Pneumonitis:
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Chronic inflam confined largely to septum
Largely monocytes & lymphocytes
Prot may escape into alveolar lumen
Seen primarily w/ Mycoplasma & viruses
Pathology typically mild (can’t be seen!)
If severe may develop Diffuse Alveolar Damage
(DAD)  clinically ARDS (adult resp dist synd)
DAD  cap damage leads to fibrin rich hyaline
membs that line alveoli.
(Both interstitial damage & hyaline formation, really
impairs resp fxn)
Acute Viral Infections:
Virus
Physical Characteristics
Influenza
ssRNA
Type A (most common & severe)
-Also B & C (only in humans)
-Susceptible to alcohol bc env.
RSV
Histology: ~rhinoviruses +
mucosal necrosis & polykaryons
Adenovirus
Histology: Cowdry Type A
inclusions intranuclear,
eosinophilc w/ halo. (~herpes)
Few polykaryons.
-4 corners strain
Hantavirus
Pulm Synd
Normal alveolar walls: Delicate,
flattened endothelial cells, crescent
rbcs, pneumocytes, macs gobble
up bad orgs, lymphs, short O2
diffusion distance
Mechanism/Pathogenesis
-Bind to resp epith
receptors
-Hemagglutinins (H1-3)
help fuse to cell memb
-Neuraminidase (N1,2)
help release from cell
-Reservoir: animals (pigs)
in rural China; human
mobility  pandemics
-Nasal dropletsURT
epith middle/lower
tract
-Viremia rare
-Severity related to TH2
resp & levels of cytokines
(Il-4,5,6,10)
-Epith necrosis
plugging of bronchioles &
alveoli by inflam cells,
mucous, necrotic cells &
fibrin.
Interstitial pneumonitis w/
thickened alveolar seta &
proteinaceous intra-alveolar
accumulations. Few macs &
lymphs (in thickened septum).
Long O2 diffusion distance (btwn cap &
alveolar lumen). RBCs, pneumocytes, &
macs in alveolar space. Can see hyaline
memb (densely pink). Caused by chems,
drugs, radiation, etc.
Prominent hyaline membs in
severe DAD. Find interstitium
(bvs inside) vs hyaline (less cells,
mostly fibrin). Exam: Won’t show
this & expect us to know it.
Examples
Transmission
Antigenicity
Clinical
-H5N1  avian
flu, poultry to
humans (%50
mortality)1
-H1N1  Swine
flu (~1000 deaths
in US from May
thru Oct 2009,
worse for
children)2
Aerosolized secretions
& hands
Strong. Point
mutations antigenic
drift; RNA recombntn
antigenic shift.3
-Young & old
vulnerable.
-Effects:
~adenoviruses, esp sec
bacterial pneumonia.
Influenzal pneumonia:
-T1 alveolar epith cells swell & slough
-Interstitium: Cap dilatation, leakage, edema
-Alveolarlumen prot “memb” against wall
-Interstitial mononuc infiltn
-T2 alv cell proliftn
T1 cell relines alveolus
-Resoltn/orgztn: fibrosis.
-Complictn: sec bact inf, in WWI streptococcus 20 mill
deaths.
Very contagious
(secretions); adults
usu immune.
~49 serotypes (few
actually cause the dx)
Vector: Rodent (deer
mouse) carried in
feces/urine
aerosolized.
Areas affected:
-Nose to bronchiole (recs of resp epith)
-May include alveolar epithsevere dx.
Effects: Necrosis & sloughing of mucosal cells.
Age: Infants & young children (MOST COMMON)
Winter
Concurrent w/ other illness or chemofatal
Ciliary damagebacterial infxns
Incubation: 2-4 d
Peak severity in 1-3 d
CSx: cough, wheezing, resp distress
CXR: interstitial infiltratesmay progress to diffuse alveolar
damage
~RSV, but NOT AGE specific (children & military)
-Causes pharyngoconjunctival fever, LRI, or gasteroenteritis.
-Severe in immunocompd pts.
-ARDS-like, severe w/ 50% mortality.
-Hemorrhageedematousresp failure
-SW USA, South Am.
-Diag by PCR & clinical.
-Rx: Ribavirin (but tough to treat).
1
Virus
Physical Characteristics
Mechanism/Pathogenesis
SARSCoronavirus
(SARS-CoV)
Measles
(Rubeola)
ssRNA
Paramyxovirus
Morphology:
-Skin: perivascular mononuc infilt
-Mucosa: focal necrosis &
ulceration
-Nodes: hyperplasia; cell fusion
polykaryons
-Warthin-Finkeldey cells w/
nuclear & cytop inclusions (>50
nuclei)
-Lungs: interstitial pneumonia;
polykaryons prominent
-Brain: acute encephalitis
CMV
Inclusion
Disease
Examples
Transmission
Antigenicity
Clinical
-Close contact.
8099 casees 11/0207/03
-Animal reservoir: ~
civet cat, bats.
-IgG abs more
common in animal
traders
-Human & Civet Cv
99.8% homology.
Signs: Fever (>38C), SOB, dry cough, pneumonia (xray/autopsy)
Fatality rate: 9.6
Diag: clinical (in-contact), epidemiology, lab, cdc.
H prot (hemagglutinin) &
F prot (Fusion) bind virus
to resp epith & aid cell
entry.
Intracell proliftncell
deathvirus disseminatn
Beta-herpes virus
-Huge nuclear enlargemt w/
large, dark inclusion w/ halo
(cytopathic effect)
Envpd.
Histology:
In fetus  widespread cellular
necrosis & inflmtn
Brain (micro/hydro encephaly,
calcificatns)
Liverspleenother
organs=necrosis DEATH
-Mostly children- prevent w/ vaccine.
-Young & malnourishedsevere dx.
-3rd W today mortality 10-25%
-Virgin soil=90%
-Organs affected: resp, conjuctiva, gut, nodes, mucosa & skin.
-Koplik spots (oral) & morbilliform rash (vasculitismaculopapular erythematous), infrq brain.
-Complications:
Bactl infection (otitis media, pneumonia)
Subacute sclerosing panencephalitis
Months later
Viral budding defect prevents release from cell
Prominent inclusions & gliosis
Slow course
Secretions (saliva,
urine, semen, cervical
secrtions,
transplacental)
-In person w/ normal immune system: no or minimal dx.
-Latent infctnsseen in donor organs.
-Young neonates or immunocompdsevere/fatal
Part of TORCH syndrome4
-One of the most common causes of fetal demise.
-Eye (chorioretinitis)
-GI (ulcers)
-Pneumonia
-Encephalitis
-Most common life-threatening complication in
transplantation. (esp lung & kidney)
1. H5N1 Strain:
-Arose in Hong Kong in 1997 from avian strain
-No human to human transmission
-Public health officials controlled by eliminating source (chickens)
-Two mutations made strain more virulent fro humans
-H5N1 returned in 2003
2. H1N1 Strain:
-“Swine” flu, arose in Mexico & US in spring 2009
-Antigenically unique from seasonal H1N1
-Higher mortality in pediatric age group (not overall higher mortality)
-Sec bacterial pneumonia
3. Strains:
-Drift-subtle antigenic changes w/in H & N (& structural prots) of strains that
yield strains slightly immunologically difft.
-Shift- Major changes (>50%) in H or N due to reassortment  occurs when 2
difft strains infect same cell – if H3N2+H1N1 simultaneously infect same cell  can yield H3N2, H1N1, H1N2, or H3N1.
-New strainsmutant strains immunologically newbecome predominant strain w/ time (allow maintenance w/in population)
-Major antigenic shiftsnew strain circulates into animal or avian reservoirsreadapt to very susceptible human population (major epidemics)
4. TORCH- Toxo, rubella, CMV, herpes. Spectrum of severe dxs in newborns.
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Histology/Pathology Chart of Acute Viral Infections:
RSV
Airway epithelium. Bronchiole SM layer can
be seen. Inflam cells below. Abnl epith
above w/ polykaryons (contain multiple
nuclei) and viral inclusions.
Syncytial cells. Dead & dying cells.
Chromatin at periphery of nucleus; eosin
glob in middle = virus.
Hyaline membs w/ severe infctn. Fibrin.
Atelectatic alveoli. On CSR appear
consolidated, not just interstitial. ~
pneumonia.
Polykaryons in resp epith. Also found in viral
culture.
Adenovirus
Nuclear inclusion. Intersititial
pneumonitis. Congested,
thickenend. Viral infection cell w/
occlusion can be seen (Cowdry
Type A)
Hantavirus Pulm Synd
Measles (Rubeola)
48 hrs later lower lobes are totally
consolidatedresp distress. Lethal!
Morbilliform rash. Starts on
facetrunk & extremities.
Maculopapular erythematous rash,
non-specific. Conjunctivitis.
Scan inflamtn is common. Rather fluid,
massive edema in the alveolar space &
eventually blood too. Thickened
interstitium. Looks ~pneumonitis, but
rather fluid.
Severe interstitial pneumonitis.
Thickened septa, congested w/ rbcs,
few inflam cells, few plykaryons (dark
pile on R), & serum exudate in alveolar
space.
“Giant cell pneumonia”. Now
consolidation w/ filling of alveolar
spaces w/ giant cells & mononucs. All
solid tissue.
CMV Inclusion Dx
Severe CMV pneumonitis. Hard to see
anatomy. Large cell in middle w/ inclusion &
halo.
Severe pneumonitis. Cytop & intranucl.
Tubule of kidney w/ CMV inclusions. Epith
cells are enlarged & have prominent
inclusions.
Warthin-Finkeldey cells. Bizarre
polykaryons. Nuclei & cytop inclusions.
Consolidation makes it hard to see
anatomy.
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Questions:
1.
2.
3.
4.
5.
6.
Which of the following viruses is transmitted via a rodent/cat vector?
a.
Hantavirus
b. Adenovirus
c.
SARS Coronavirus
d. Measles Paramyxovirus
e. CMV
f.
Influenza
Which of the following viruses have Kopliks spots clinically and Warthin-Finkeldey cells + Polykaryons histologically?
a.
Hantavirus
b. Adenovirus
c.
SARS Coronavirus
d. Measles Paramyxovirus
e. CMV
f.
Influenza
Which of the following viruses are most likely to lead to encephalitis?
a.
Hantavirus
b. Adenovirus
c.
SARS Coronavirus
d. Measles Paramyxovirus
e. CMV
f.
Influenza
Which of the following viruses are NOT age specific w/ Cowdry Type A inclusions histologically?
a.
Hantavirus
b. Adenovirus
c.
SARS Coronavirus
d. Measles Paramyxovirus
e. CMV
f.
Influenza
Which of the following viruses bind to resp epith recs, fusion is helped by hemagglutinins, and release from the cell is helped by neuraminidases?
a.
Hantavirus
b. Adenovirus
c.
SARS Coronavirus
d. Measles Paramyxovirus
e. CMV
f.
Influenza
The following images are indicative of which viruses?
a.
b.
c.
d.
e.
4
Answers:
1.
2.
3.
4.
5.
6.
a&c
d
d&e
b
f
a. Hantavirus, b. RSV, c. Adenovirus, d. Measles, e. CMV.
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