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383 Cards in this Set

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  • Back
what is the value of the pleural pressure during normal respiration?
negative
which bronchus is more inline with the trachea and is therefore more susceptible to aspiration bodies?
Right main bronchus
what type of epithelium is found in the bronchus?
pseudostratified, ciliated epithelium
what type of epithelium is found in the bronchiole?
simple columnar, ciliated
define deadspace
the area in the respiratory system where there is no gas exchange
give an example of a disease in which there is increased physiological deadspace
emphysema
which type of alveolar cells secrete surfactant?
Type II alveolar cells
major component of surfactant?
phospholipids
function of surfactant?
decreases surface tension, thereby preventing alveolar collapse
(also decreases intra-alveolar fluid accumulations)
at what point in respiration is the resistance of the lung the least?
when the lung is fully inflated (at the end of inspiration)
what happens to resistance as lung volume decreases (expiration)?
resistance becomes greater
give an example of a lung disease that is significantly effected by dynamic closure.
emphysema
(high pressures move equilibratory point down to an area where the airway is collapsible. collapsible airways cause wheezing (or even collapse) upon respiration.
at which week of gestation does formation of the respiratory tract begin?
week four
when does alveolar development:
1. begin
2. complete
1. 34 weeks gestation
2. two years of age
what are Clara cells?
non-ciliated cells that accumulate and detoxify some agents
what are Kulchitsky cells?
neuroedocrine cells
*secrete vasoactive amines and hormonally active polypeptides*
chronic irritation causes the epithelium of the lung to change from ? to ?
columnar (simple or pseudostratified) to squamous
what is the Reid index?
ratio of the thickness of the mucous glands to the thickness of the bronchial wall.
what is an example of when the Reid index would be increased?
chronic bronchitis
T/F: cartilage and mucous secreting glands are found in the BRONCHIOLES
False
what cells are found in the bronchioles?
*significance?
non-ciliated Clara cells
* clearance of airborne particles is difficult in the bronchioles due to the lack of ciliated cells*
the respiratory unit of the lung is known as ?
an acinus
what lung components make up an acinus?
respiratory bronchioles
alveolar ducts
alveoli
what type of membrane is found between the alveoli?
fused basement membrane
a congenital abnormality of the lung in which incomplete or defective development occurs is called?
pulmonary hypoplasia
what is an example of compression of the lung that results in pulmonary hypoplasia?
diaphragmatic hernia
what is another important cause of pulmonary hypoplasia?
oligohydramnios
what is the difference between intra- and extra- lobular sequestration?
1. intralobular occurs within the visceral plerua
2. extralobular occurs outside of the visceral pleura
diseases that present with hoarsness or voice changes are most likely diseases of?
the larynx
which type of reactive lesion of the larynx is caused by HPV?
squamous papilloma
rarely progresses to cancer
95% of laryngeal carcinomas are of what type?
squamous cell carcinomas
most squamous cell carcinomas of the larynx are caused by?
irritation (esp. tobacco smoke)
infections seen in the bronchi and bronchioles are most common in what age group?
children
what is the significance of a smoker who inhales irritant gases?
many are oxidants and compound the chronic exposure to tobacco smoke
effects of ozone on airways?
makes airways more reactive and exacerbates asthma and other lung diseases
which irritant gas is found in industrial environments or decaying grain?
nitrogen dioxide
why is carbon monoxide so lethal?
binds hemoglobin, preventing oxygen biding and transport
inert matter (that may be smaller than vision allows) can cause diseases of the bronchi and bronchioles. what is another name for this matter?
particulate matter
a nonspecific granulomatous response in the bronchial tree is known as?
bronchocentric granulomatosis
what organism is known to cause bronchocentric granulomatosis in asthmatic patients?
Aspergillus
constrictive bronchiolitis involves constriction from?
submucosal thickening of bronchiolar wall
constrictive bronchiolitis will produce what pattern of lung disease?
obstructive pattern
what is bronchiectasis?
abnormal dilatation of the bronchi
from what do most lung tumors arise?
bronchial epithelium
what happens after prolonged atelectasis?
fibrotic scarring of the lung occurs
describe what happens in resorptive/obstructive atelectasis
*caused by an obstruction or mucous plug of bronchus
*residual air is resorbed and the lung collapses distal to the obstruction
when the pleural cavity is filled with fluid or air, what type of atelectasis may occur?
compression atelectasis
which type of atelectasis is generally irreversible and what causes it?
contraction atelectasis
*occurs when scarring and contraction of the pleura prevents lung expansion
fluid within the alveoli is known as?
pulmonary edema
what type of fluid is usually in the alveoli in pulmonary edema?
transudate
what am I called?
rapid onset of severe, life threatning respiratory insufficiency, tachy, cyanosis, severe arterial hypoxemia that is refractory to oxygen therapy?
ARDS
adult respiratory distress syndrome
mortality rate of ARDS?
~60%
pathogenesis of ARDS?
1. initial lesion is damage to alveolar wall
2. followed by vascular leakage, cell sloughing, edema, hyaline membrane formation, atelectasis
3. PROTEINACEOUS fluid accumulation is important in pathogenesis
4. compliment and cytokines play critical roles
5. Type II cell proliferation and interstitial inflammation, organization, fibrosis
6. fibrosis may resolve or death may result
what is the most common cause of ARDS?
shock/sepsis
respiratory distress syndrome in infants is called?
hyaline membrane syndrome
what defines the two stages of ARDS?
1. acute stage, cellular
2. organization stage, fibrosis
how long after the onset of the acute stage does the organization stage of ARDS begin?
~1wk
obstructive lung disease is caused by?
increased resistance to airflow from partial or complete obstruction at any level.
restrictive lung disease is caused by?
reduced capacity of lung due to decreased expansion of parenchyma
which disease type is known as a volume/capacity disease?
restrictive lung disease
which disease is known as an airway disease?
obstructive lung disease
chronic bronchitis is what type of lung disease?
obstructive
asthma is what type of lung disease?
obstructive
ARDS is what type of lung disease?
restrictive
(hyaline alveolar membranes)
bronchiolitis is what type of lung disease?
obstructive
pneumoconiosus is what type of lung disease?
restrictive
interstitial/infiltrative lung disease is what type of lung disease?
restrictive
bronchiectasis is what type of lung disease?
obstructive
what is the major clinical symptom seen in obstructive lung disease?
dyspnea
what type of "chest" is seen in a COPD patient?
barrel chest
what are the three major components of COPD?
1. emphysema
2. chronic bronchitis
3. small airway obstruction
what difference in the PFT would you see in a person with COPD?
decrease in FEV
what is panacinar emphysema?
emphysema involving the entire acinus from the respiratory bronchioles to the terminal acinus
describe centrolobular emphysema
emphysema involving the respiratory bronchiole only
(the terminal acinus is normal)
where in the lung is centrolobular emphysema the worst?
upper lobes
apical segments
where is paraseptal emphysema located?
along the pleura and perilobular space
what is bullous emphysema?
any form of emphysema resulting in air spaces over 1cm.
describe senile emphysema
larger ducts and smaller acini; seen with aging; elasticity is normal
which type of emphysema is seen in a-1-antitrypsin deficiency?
panacinar
which type of emphysema is most common in smokers with chronic bronchitis?
centrolobular
which organ makes alpha-1-antitrypsin?
liver
function of a-1-antitrypsin?
protects alveoli from destruction by inflammatory cell proteinases (trypsin, elastase)
what is a major source of elastase seen in the pathogenesis of emphysema?
chronically irritated neutrophils and macrophages
changes seen in a PFT with emphysema? (3)
1. decreased FEV1
2. decreased FVC
3. increased RV
a persistent cough with sputum production for at least 3 months in two years is known as?
chronic bronchitis
what would the Reid index be in a patient with chronic bronchitis?
increased
(more mucous and serous glands)
in severe cases of chronic bronchitis there may be obliteration of the bronchial lumen, also known as?
bronchiolitis obliterans
In COPD, when is a person called a "blue bloater?"
when chronic bronchitis symptoms dominate
(also cor pulmonale, obese)
in COPD, when is a person called a "pink puffer?"
when empysema symptoms dominate the disease
(thin, pursed lips)
what is bronchiectasis?
chronic necrotizing infection of the bronchi and bronchioles leading to abnormal permanent dilatation.
what side does bronchiectasis most commonly occur on?
Left side
avg. age of onset of bronchiectasis?
first two decades
in what respiratory disease is bronchiectasis commonly seen?
CF
what is asthma that is refractory to aggressive treatment called?
status asthmaticus
(results in death)
which antibody mediates Type I hypersentivity asthmatic reactions?
IgE
describe the acute phase response in a type I hypersensitivity asthmatic rxn
antigen exposure, binds to IgE receptor of mast cells
- results in release of mediators (histamine, leukotrienes, prostaglandins, cytokines)from the mast cells
- these mediators trigger bronchiospasm, bronchoconstriction, edema, mucous secretion
describe the late phase response.
seen 4-8 hrs. later
- caused by cells recruited in the acute phase (neutrophils, basophils, lymphocytes, eosin.)
- additional mediator release and epithelial cell damage
which drug is known to trigger asthma (along with triggering nasal polyps)
aspirin
what happens in exercise induced asthma?
physical activity induces bronchospasm
what causes microvascular pulmonary edema
usually injury related
- leakage of capillaries within alveoli
histologically, what is seen in pulmonary edema as a result of heart failure?
hemosiderin laden macrophages in alveoli
describe a "saddle" pulmonary embolus
large thrombus at the bifurcation of the pulmonary artery - cuts off ALL pulmonary circulation. Cause of sudden death.
describe the symptoms seen in a peripheral embolus
sudden onset SOB, chest pain, tachycardia
what is the value that, above it, is called pulmonary hypertension?
25mm Hg
describe the morphology of pulmonary hypertension at the pulmonary artery level.
- hypertrophy of media of pumlonary arteries
- followed by intimal proliferation and fibrosis
- plexiform lesions form in wall - these lesions dilate
- results in hemorrhage and fibrinoid necrosis of the arteries and arterioles
what is "pre capillary" pulmonary hypertension?
increased resistance in pulmonary arteries prior to capillary beds
causes of precapillary pulmonary hypertension? (3)
1. primary pulmonary HTN
2. L to R shunts
3. recurrent pulmonary emboli
what is "post capillary" pulmonary hypertension?
increased resistance in post capillary vasculature
causes of post capillary HTN? (3)
1. LV cardiac failure (back up in lungs)
2. mitral stenosis
3. pulmonary veno-occlusive disease
what type of antibodies are seen in goodpasture's syndrome?
anti-glomerular basement membrane antibodies
pulmonary manifestations of goodpastures?
hemorrhagic necrotizing interstitial pneumonia
what is the triad of symptoms seen in Wegeners Granulomatosis?
1. necrotozing angiitis
2. aseptic necrosis/granulomas of lungs and upper respiratory tract
3. glomerulonephritis
Goodpastures and Wegeners are collectively known as?
diffuse Pulmonary Hemorrhagic syndromes
in relation to restrictive lung diseases, describe the:
1. oxygen diffusing capacity
2. lung volume
3. compliance
4. elasticity
1. reduced oxygen diffusing capacity
2. reduced lung volume
3. reduced compliance
4. increased elasticity
what is another name for most restrictive lung diseases?
interstitial lung disease (due to fibrosis)
the following disease belong to which class of lung diseases?
usual interstitial pneumonia (UIP)
Desquamative intstitial pneumonitis (DIP)
Bronchiolitis obliterans
hypersensitivity pneumonia
Diffuse Interstitial Lung Disease
of the diffuse interstitial lung diseases, which is the most common type?
UIP
of the diffuse intersitial lung diseases, which has the worst prognosis?
UIP
(87% mortality, avg. survival 103 yrs)
what is the average age of onset of UIP?
5th-6th decade
UIP is also associated with an increased occurance of?
bronchogenic carcinoma
which area of lungs is most often involved in UIP?
base and pleural surface
In UIP, what is seen histologically?
heterogenous cellularity and fibrosis
grossly, what is seen in UIP?
honeycomb change
knobby pleural surfaces ("muscular cirrhosis")
what do we mean when we say temporal heterogeneity is seen in UIP?
cellular areas alternate with fibrotic areas
in desquamative interstitial pneumonitis (DIP), what is seen in the alveoli?
large aggregation of monocytes in alveoli
(also minor interstitial fibrosis)
what would be seen in an X-ray of a DIP patient?
ground glass infiltrates
treatment for DIP?
steroids
(good response)
which cell type is hyperplastic in DIP?
type II pneumocytes
what is bronchiolitis obliterans?
fibrosing inflammatory process that occludes the lumen of the small airways
what is BOOP?
bronchiolitis obliterans with organizing pneumonia
what is bronchiolitis obliterans?
fibrosing inflammation that occludes the lumen of the small airways
what are some possible etiologies of BOOP?
1. infections
2. toxins
3. obstruction
4. aspiration
5. collagen vascular disease
which virus is often seen as a cause of BOOP?
RSV
describe the condition of the distal airways as seen in bronchiolitis obliterans
distal airways are overinflated and/or filled with cellular debris (macrophages, lipids, cholesterol)
what are some toxins that are known to cause bronchiolitis obliterans? (3)
1. nitrogen oxides (silofillers disease)
2. ammonia
3. acids
T/F: a tumor can cause bronchiolitis obliterans
TRUE
tumors are considered obstructions that can cause bronchiolitis obliterans
what causes hypersensitivity pneumonia?
prolonged exposure to dust allergens
how is hypersensitivity pneumonia different from asthma?
the reactive site is the alveolus
(the reactive site in asthma is the airway)
what type of hypersensitivity rxn. occurs in hypersensitivity pneumonia?
early: Type III immune-complex rxn
late: type IV hypersensivity response
describe the histopath seen in hypersensitivity pneumonia
granulomas frequently seen
macrophages, lymphocytes
if chronic: fibrosis and honeycombing
what are some allergens that oftentimes lead to hypersensitivity pneumonia?
bird dander
mold
actinomycosis
trichosporon
much more...
how is hypersensitivity pneumonia distinguished from pneumoconiosis?
hypersens. pneum: allergic reaction varies by individual
pneumoconiosis: all individuals react the same
treatment for hypersensitivity pneumonia?
steroids
removal of allergen if possible
what causes pneumoconiosis?
dust inhalation
what are some factors regarding the inhaled dust that lead to pathogenicity?
1. Amount of dust inhaled
2. Size and shape of dust particles
3. solubility and physiochemical properties
4. presence of additional irritants
what is the most dangerous sized particle?
1-5 microns
these are the ones that reach small airways and alveoli
what happens once the dust is inhaled that causes damage?
they produce a fibrotic response
which intrinsic defense mechanism removes inhaled larger particles?
mucociliary epithelium
which intrinsic defense mechanism is geared towards the particles that reach the alveoli?
alveolar macrophages
what is Caplans syndrome?
a triad of:
1. pneumoconiosis
2. rheumatoid arthritis
3. pulmonary rheumatoid nodules
T/F: coal workers pneumoconiosis is associated with an increased cancer risk
FALSE
no increased CA risk
describe the following stages of coal workers pneumoconiosis:
1. macule
2. nodule
3. complicated
4. progressive massive fibrosis
1. aggregates of fibrosis with surrounding emphysema
2. fibrotic (>2.5 cm)
3. more than one lesion; symptomatic
4. end stage; large consolidated area; significant symptoms; RARELY OCCURS WITHOUT CONCURRENT Si OR TOBACCO EXPOSURE
what are the terminal complications of pulmonary massive fibrosis? (2)
1. cor pulmonale
2. RV hypertrophy
what is the most toxic form of inhaled silica?
crystalline silica (quartz)
describe acute silicosis
-rapidly develops, high mortality
-short term, high doses of small particle silica
-diffuse fibrosis of lung; dense eosinophilic material in alveoli
describe simple nodule (chronic) silicosis
-pulmonary fibrosis WITH collagenous nodules
- concentric collagen bundles surrounding clear needle shaped spaces of silica
- larger particles; longer, lower exposure
chronic silicosis is associated with an increased risk of?
TB
(at least 30x)
asbestos causes an increased risk of?
mesotheliomas
describe the morphology of asbestosis
- diffuse interstitial fibrosis w/asbestos fibers
- circumscribed, dense, hyalinized or calcified plaques on pleura and diaphragm.
what is siderosis?
iron dust exposure
(usually not significant)
what is the difference between the acute and chronic forms of berylliosis?
1. acute - similar to an allergic response, no granulomas
2. chronic - non-caseating granulomas, diffuse interstitial reaction
which two types of "bodies" are seen in berylliosis?
1. Schaumann body (protein, calcium, iron)
2. Asteroid bodies (lipoprotein aggregates in a giant cell)
what is Loeffers Syndrome?
transient pulmonary lesions and eosinophilia; probably an allergic reaction
what is microfilaria?
when a worm or mite produces an eosinophilic response
describe the lung involvement seen in Scleroderma
- diffuse fibrosis and vascular thickening
- lung involvement usually the fatal component of the disease
- honeycombed changes
result of pulmonary vascular intimal thickening seen in scleroderma?
pulmonary hypertension
describe the lung involvement seen in RA
- rheumatoid nodules in lungs (especially pleural and subpleural locations)
- caplan's syndrome
describe the lung involvement seen in Sjogren's syndrome
- lymphoid infiltrate in peribronchiolar and bronchial glands
- increase in lymphomas
describe the lung involvement seen in SLE?
- infections and pleural effusions
- hemorrhage and vasculitis
describe pulmonary alveolar proteinosis
- protein deposits in alveoli
- few inflammatory cells
- protein is similar to surfactant but without surfactant properties
- thought to be an imbalance of phospholipid production and clearance
describe the disease course of pulmonary alveolar proteinosis
1/3 resolve spontaneously
1/3 improve with pulmonary lavage
1/3 don't respond to any therapy
stereotypical sarcoid patient?
adult 20-40 yrs
woman
black
sarcoid is characterized by?
- non-caseating granulomas
- bilateral lymphadenopathy with hilar involvement
besides the lungs, what other organs does sarcoid commonly effect?
heart
CNS
skin
oral cavity
what is Lofgren's syndrome?
erythema nodosum
what is Mikulicz' syndrome?
bilateral sarcoidosis of lacrimal, sublingual, submaxillary, parotid glands
common histopath seen in sarcoidosis?
- giant cells containing asteroid bodies
- Schaumann bodies
- GRANULOMAS
which type of pulmonary carcinoma makes up >90%?
bronchogenic carcinoma
what age average does bronchogenic carcinoma most commonly occur in?
peak incidence in 6th and 7th decade
(rare before 40 yrs)
80% of lung cancers occur in ?
smokers
give an example of radiation that increased rates of lung cancers.
Uranium miners
Atomic bomb survivors
1. 20% of deaths in asbestos workers is due to?
2. 10% of deaths are due to?
1. bronchogenic carcinomas
2. mesotheliomas
what gas, found in the ground, is known to induce lung cancer?
Radon
which disease, associated with pulmonary scarring, has increased rates of lung cancer?
scleroderma
which type of lung carcinoma is the most lethal?
small cell carcinoma
what is the important distinction that must be made when trying to figure out the type of lung cancer? why?
small cell cs. non small cell

treatment differs: small cell considered nonresectable, others can be resected
where do most bronchogenic carcinomas arise?
central airways
where do adenocarcinomas arise?
terminal bronchioles (Clara cells)
where do bronchioloalveolar carcinomas arise?
terminal bronchioles (Clara cells)
what is an:
1. exophytic lesion
2. endophytic lesion
1. grows into lumen
2. grows into parenchyma
where does lung cancer like to metastasize to? (4)
in order of preference:
1. adrenals
2. liver
3. brain
4. bone
which type of lung cancer has a close correlation with smoking?
squamous cell carcinoma
(also small cell carcinoma)
what histologic features are seen in squamous cell carcinoma? (2)
keratin
intercellular bridges
where in the lung does squamous cell carcinoma usually occur?
centrally (near hilum)
why do we see cavitating squamous cell carcinomas?
center of the tumor undergoes necrosis and cavitates
what is the most common cancer found in women and nonsmokers?
adenocarcinoma
where in the lung does adenocarcinoma tend to occur?
peripherally
what are the two histologic forms of adenocarcinoma?
1. typical bronchial derived adenocarcinoma
2. bronchioalveolar carcinoma
which has a faster growth rate: adenocarcinoma or squamous cell carcinoma?
squamous cell carcinoma
where do bronchioalveolar carcinomas like to grow?
along pre-existing structures (such as alveolar walls)
what would bronchioalveolar carcinoma look like on Xray?
would look like infiltrates suggesting a pulmonary infection
treatment for bronchioalveolar carcinoma?
resection
(these are usually well-circumscribed tumors)
small cell carcinoma is thought to arise from which cell type?
Kulchitsky's cells (neuroendocrine cells within the bronchial epithelium)
significance of small cell carcinoma arising from neuroendocrine cells?
tumor often secretes neuropeptides causing paraneoplastic syndromes
in SCC: tumor state at time of diagnosis?
generally have metastasized widely
what effects can some lung tumors have on the superior vena cava?
cause SVC syndrome (crush the SVC)
when the tumor causes a nerve entrapment syndrome: what symptoms present when the following nerves are trapped?
1. recurrent laryngeal n.
2. phrenic n.
3. sympathetic system
1. hoarseness
2. diaphragmatic paralysis
3. Horners syndrome
what is tylosis?
hyperkeratosis (callous formation)
caused by a type of paraneoplastic syndrome
in metastatic lung cancer: when would you see leukoerythroblastosis?
when there is bone marrow involvement
what is the 5 yr survival rate of lung cancer in general?
<9%
dismal prognosis
what would a bronchial carcinoid look like?
small projections into the lumen of the bronchus covered by bronchial epithelium
(good prognosis-metastisizes locally)
what is responsible for most of the symptoms seen in bronchial carcinoid syndrome?
obstruction or hemoptysis
where are mucoepidermoid carcinomas most often found?
proximal bronchi or trachea
what is a hamartoma?
an abnormal overgrowth of tissues in an abnormal pattern (not malignant)
how can a malignant mesothelioma be distinguished from an adenocarcinoma?
by molecular markers
which virus am I?
- member of the herpesvirus family
- causes pneumonitis that can result from a primary infection or from latent reactivation
- has a 35-50% mortality rate in a bone marrow allograft patient that catches it?
CMV
causes cytomegalovirus pneumonitis
the hantavirus belongs to which virus family?
Bunyaviridae
describe the genome of the hantavirus
(-)ssRNA
trisegmented (3 separate RNA pieces)
how is hantavirus transmitted?
aerosolized rodent urine
what are the three characteristics seen in Hantavirus Pulmonary Syndrome (HPS)?
1. pulmonary edema
2. shock
3. diuresis
~ fatality rate of a hantavirus infection?
30-40%
which rodent is the primary carrier of sin nombre virus?
deer mouse
what would you see in the following lab values in HPS?
1. platelet count
2. lymphocytes
3. WBC differential
4. hematocrit
1. low
2. atypical
3. Left shift
4. elevated
what about these values in HPS?
1. albumin
2. LDH, AST, ALT
1. low
2. elevated
how is HPS managed?
EARLY:
1. aggressive supportive care (ventilation too)
2. inotropes (dobutamine)
3. careful monitoring of oxygenation, fluid balance, BP
which test is used to diagnose influenza?
rationale?
hemaglutination inhibition titer
*can see antibodies made in response to the flu
which family of viruses does the influenza belong to?
orthomyxoviruses
which influenza strain causes pandemic flu and also infects other animals?
infuenza A
which influenza strain causes epidemic flu and only infects humans?
infuenza B
which influenza strain only causes mild disease and only infects humans?
influenza C
what two animals are important reservoirs for influenza A?
pigs
waterfowl
describe the virion and nucleocapsids of influenza
enveloped virion
helical nucleocapsids
describe the genome of influenza
segmented
(-)ssRNA
1. influenza A and B have how many RNA segments?
2. what about influenza C?
1. 8
2. 7
each segment encodes 1 or 2 gene products
what are the two important antigenic determinants found on the influenza A surface?
Hemagglutinin (HA)
Neuraminidase (NA)
function of hemagluttinin?
facilitates attachment to and fusion with host membrane
function of neuraminidase?
- allows penetration through respiratory secretions
- prevents viral aggregation
what binds to viral RNAs and serves as a group specific antigen (A,B,C classification)?
neucleocapsid protein (NP)
what is the function of membrane protein (M1)?
matrix protein
binds to nucleocapsids during maturation
what is the M2 protein?
an ion channel - important for uncoating
*activity inhibited by amantidine and rimantidine
which receptors on the host cell does influenza A bind to?
scialic acid receptors
what causes HA to change its conformation?
what change occurs?
acidification of the endosome causes conformational change
- change exposes hydrophobic residues for fusion
acidification of the endosome also opens ____, which promotes uncoating.
M2 ion channel
what happens to the viral genome once uncoating occurs?
it is transported to the nucleus
because the RNA of influenza virus is (-), what is needed for viral gene expression?
cellular RNA polymerase
describe the production of mRNA in influenza A
1. viral polymerase with endonuclease activity is complexed to 5' end of host mRNA.
2. this 5' end is used as a primer for (-) viral RNA synthesis
3. this results in destruction of the host proteins: the cell will hereafter make viral proteins
what are the 3 proteins the influenza viral polymerase is composed of?
1. PB1 (binds to cap of host mRNA)
2. PB2 (endonuclease)
3. PA
does synthesis of the (+)RNA (antigenome)of influenza require priming by cellular mRNA?
NO
(only replication of the (-)RNA strand requires the primer)
where are HA and NA inserted?
into the plasma membrane
(this is the site of virion budding)
when do influenza epidemics occur?
winter or early spring
how often to influenza pandemics occur?
3-4 times a century
how is influenza transmissed?
respiratory droplets
is influenza a "hardy" virus?
YES
it remains infective for up to 24 hrs after aerosolization!
what causes antigenic drift in influenza?
minor changes in the antigenicity of HA and NA (due to point mutations)
what causes antigenic shift in influenza?
reassortment of HA or NA RNA segments when two viruses infect the same cell (an entirely new gene is encoded)
significance of antigenic shift?
unpredictable
can lead to epidemics and/or pandemics
why is antigenic drift so prone to occur in influenza?
because of an error-prone viral RNA-dependant RNA polymerase
there are 5 antigenic sites in the globular head of the H protein. how many antigenic sites must have mutations before antigenic drift occurs?
two or more sites must be mutated
why are pigs such a "scary" infuenza reservoir?
reassortment can occur in pigs: then the "new" virus subtype is transmitted to humans
mortality rate of H5N1?
51%
what is the incubation period of influenza virus?
1-5 days
(avg of 2)
what effect does influenza have on mucous and how does this occur?
NA activity reduces viscosity of mucous allowing the virus to attach to cells
once the virus attaches to the cells, what happens?
desquamation of ciliary epithelium occurs (via degeneration of respiratory epithelial cells)
significance of impaired mucociliary escalator?
prevents extrusion of virus
increases susceptibility to secondary infections
what leads to the cough and tracheal irritation?
tracheobronchial inflammation
if systemic spread is uncommon in an influenza infection: why is there myalgia and other systemic effects?
circulating cytokines cause these
(myalgia = IL-1 activated prostaglandin E2, which activates lysosomal proteases, which "chew" on muscle)
how long after onset does it take for the fever and systemic effects subside?
3-5 days
what about the duration of respiratory complaints in an influenza infection?
cough etc. may persist for 2-4 weeks
complications of influenza? (3)
1. viral pneumonia
2. bacterial pneumonia
3. CNS manifestations
what is the flu vaccine composed of?
2 A types
1 B types
flu vaccine is recommended for?
ALL high risk groups >6 months of age
high risk includes:
1. adults >65 yrs
2. children 6-23 months
3. nursing home residents
4. individuals with pulmonary/CV disorders
5. children receiving long term aspirin therapy (prevent Reye syndrome)
treatment for flu infection?
1. NSAIDs
2. amantidine, rimantidine (if <48 hours after onset, only for Influenza A)
3. neuraminidase inhibitors (Zamivir or oseltamivir) to reduce duration of symptoms
which group of viruses do the following belong to?
RSV, parainfluenza, humanmetapneumovirus (hMPV), Mumps, measles
paramyxoviruses
which paramyxovirus is a major cause of acute bronchiolitis and pneumonia in infants?
RSV
which virus is a major cause of croup?
parainfluenza
which virus is a common cause of respiratory disease in young children?
human metapneumovirus (hMPV)
which virus causes parotitis, orchitis, meningitis?
mumps
describe the virion and nucleocapsid structure of the paramyxovirus
enveloped virion
helical nucleocapsid
describe the genome of the paramyxovirus
monopartite
(-)ssRNA
describe the hemagglutinin and neuraminidase activities of the paramyxovirus
located on a single protein (HN)
do all paramyxoviruses have an HN protein?
NO
RSV lacks HN, but has G protein instead
what is the function of the F protein in paramyxoviruses?
promotes virion-cell and cell-cell fusion
regarding paramyxovirus replication:
1. attachment to cell is via?
2. penetration is via?
1. HN or G protein
2. F protein (endocytosis not required)
regarding paramyxovirus replication:
1. what transcribes the genome to produce both mRNAs and the (+)ssRNA antigenome?
2. where does the entire replication cycle occur?
1. virion RNA polymerase
2. cytoplasm
in paramyxovirus: viral glycoproteins are expressed on the infected cell surface. what do these promote?
cell-cell fusion
production of giant cells (synctia)
how do paramyxoviruses exit host cell?
budding from plasma membrane
what is the advantage of syncytia formation?
the virus can move from cell to cell directly and antibodies can't get at them while they are inside the cell
what general type of replication is seen in the paramyxoviruses?
start/stop replication
- gradient of expression of different proteins
what is the most virulent type of parainfluenza virus (PIV)?
PIV-3
(causes croup, bronchitis, pneumonia in children <1yr)
which type of PIV is usually asymptomatic?
PIV-4
describe the immunity gained after a PIV infection
short duration
re-infections are common but usually less severe
1. when do PIV-1 and PIV-2 cause croup epidemics?
2. when does PIV-3 cause croup epidemics?
1. Autum
2. late winter or spring
transmission of PIV?
respiratory droplets
direct contact with fomites
which type of PIV is known for nosocomial infections?
PIV-3
(most virulent type)
1. incubation period of PIV
2. duration of shedding?
1. 2-6 days
2. ~1 wk
where does PIV normally multiply?
epithelial cells of URT
croup is characterized by?
barking cough
usually worse at night
inspiratory stridor (with inspiratory retractions and tachypnea)
respiratory distress
three treatments used for symptomatic control in croup?
huimidification of inspired air
racemic epinephrine (reduces edema)
dexamethasone (reduces edema)
most important respiratory pathogen among infants and young children in temperate zones worldwide?
RSV
transmission of RSV?
direct contact
respiratory droplets
fomites
RSV causes the most severe infections in?
infants <6 months
when do annual epidemics of RSV occur?
midwinter
where does RSV replicate?
ciliated epithelial cells
(buds from apical portion of cell into lumen)
RSV often causes plugs that obstruct airflow. where are these plugs found and what are they made of?
found in small airways
made of mucous, cellular debris, fibrin
s/s of obstruction?
expiratory wheezing
focal atelectasis
three severities of RSV infection?
1. mild URT disease
2. severe bronchiolitis
3. bronchopneumonia
incubation period of RSV?
4-5 days
RSV can increase morbidity and mortality in adults with?
underlying conditions
COPD
CHF
asthma
is RSV hardy?
NO
it is extremely labile - inoculate directly into cell culture when gathering a specimen
there is a strong association between RSV bronchiolitis and ?
subsequent development of asthma
what can we do to decrease the number of RSV hospitalizatons in immunocompromised people?
give RSV antibodies once a month during RSV season
what is the name of a monoclonal anti-F antibody given to prevent RSV?
palivizumab
which virus presents and has a clinical course similar to RSV?
hint: it was discovered in 2001
human metapneumoviruses
what time of year is mumps epidemic in:
1. urban areas
2. rural areas
1. mumps is endemic year round in urban areas
2. late winter and spring in rural areas
how long does immunity to mumps last?
lifelong
how is mumps transmitted?
salivary secretions
respiratory aerosols
where is the replication site for mumps?
URT epithelium
(from there it establishes viremia)
incubation period of mumps?
18-21 days
mumps symptoms usually resolve in?
1 wk
complications of mumps? (3)
orchitis
meningitis
deafness
what type of vaccine is the mumps vaccine?
live attenuated
(part of MMR)
four most common viruses that infect the URT?
in order of occurrence:
1. rhinovirus
2. coronavirus
3. enterovirus
4. adenovirus
rhinoviruses are members of which viral family?
picornavirus
describe the virion and capsid of the rhinovirus
naked virion
icosahedral capsid
describe the genome of the rhinovirus
small
(+)ssRNA genome
(pico=small)
the rhinovirus genome encodes what four structural proteins?
VP1-VP4
function of VP1
antigen for neutralizing antibodies
regarding rhinoviruses:
1. optimal growth temp?
2. optimal growth pH?
1. 33 deg.C (below core body temp)
2. 6.8-7.3
implications of rhinovirus being acid sensitive?
inactivated at pH 3-5 (stomach acid)
this limits the infection to the URT
which host receptors does the rhinovirus bind to? (2)
1. ICAM-1 receptors
2. LDL receptors
does the rhinovirus undergo acidification in the endosome?
NO
the RNA is delivered directly into the cell
general mechanism of rinovirus replication?
polyprotein expression
which protein directs the synthesis of (-)ssRNA antigenome and (+)ssRNA genome?
VPg protein
what must happen to the newly synthesized protein in order for the virus to become infectious?
viral protease must cleave VP0, generating VP2 and VP4
what are the two rhinovirus seasons?
early fall
late spring
transmission of rhinovirus?
hand contact
self inoculation
what is the usual portal of entry for rhinovirus?
nose
incubation period for rhinovirus?
1 day
SHORT!
describe the pathogenesis of a rhinovirus infection
1. rhinovirus enters nose
2. transported by mucociliary action to nasopharynx
3. multiplies in nasopharyx
4. causes inflammation and increased nasal secretions
where does rhinovirus replicate?
epithelium of nasal mucosa and nasopharynx
rhinovirus causes release of what inflammatory mediators?
histamine
prostaglandins
ILs
describe the mucous discharge as the rhinovirus infection progresses.
becomes more mucopurulent (due to increased presence of neutrophils)
why is a fever good in a rhinovirus infection?
increased temp limits replication of rhinovirus
how do you tell the difference between a rhinovirus infx and strep throat?
strep:
less nasal involvement
less frequency of cough
more severe pharyngeal discomfort
how do you tell the difference between a rhinovirus infx and the flu?
flu:
more frequent occurrence of fever
more severe malaise, myalgia, cough
how do you tell the difference between a rhinovirus infx and secondary acute bacterial sinusitis (SABS)?
SABS:
very severe (meningitis, brain abcess)
less severe cases present like a flu that won't go away
what happens when you give ASA, antihistamines and NSAIDs.
you get symptomatic relief but you get a longer cold duration.
what are two enteroviruses that cause s/s similar to rhinovirus?
coxsackie A/B
Echovirus
SARS belongs to what kind of virus group?
coronaviruses
which two antigenic groups of coronavirus are associated with the common cold?
229E
OC43
describe the virion and nucleocapsid of a coronavirus
enveloped virion with protruding glycoprotein spikes
helical nucleocapsid
describe the genome of the coronavirus
LARGE
(+) ssRNA
in the coronavirus: which protein is thought to function in receptor binding, viral cell fusion and as an antigen for neutralizing antibodies?
S (spike) glycoprotein
regarding coronaviruses: how is viral entry accomplished
via Fusion between the viral envelope and the plasma membrane
describe replication of the coronavirus
1. (+)ssRNA translated to produce RNA-dependant RNA polymerase
2. (-)ssRNA antigenome synthesized - serves as a template for production of subgenomic mRNAs.
3. mRNAs form a "nested set" with a common 3' end
4. S and HE glycoproteins are inserted into ER membranes and processed in the Golgi
how are the virions formed?
via budding at the RER and Golgi
seasons for coronavirus infections?
winter
spring
how often do coronavirus epidemics occur?
every 2-3 yrs
transmission of coronavirus?
respiratory route
difference in s/s between coronavirus and rhinovirus infections?
clinically indistinguishable
transmission of SARS-CoV?
close person to person contact
respiratory droplets
SARS is thought to have originated from which animal?
bats
how long after incubation of SARS does lower respiratory phase begin?
s/s?
3-7 days
(dry, nonproductive cough, dyspnea)
where does SARS replicate?
outside of the lungs
(causes increased liver enzymes)
at the peak of a SARS infection, describe:
1. WBC
2. platelet count
1. low
2. low
in which virus are 50% of infections asymptomatic?
hint: known to cause respiratory illness, ocular disease, gastroenteritis...
adenovirus
describe the virion and capsid of the adenovirus infection
naked virion
complex icosahedral capsid
- fibers at pentons serve as viral attachment proteins and important antigens
- hexon protein also an important antigenic determinant
describe the genome of adenovirus
LARGE
dsDNA
40 human serotypes (each associated with a different disease)
is the adenovirus "hardy"?
yes
it is resistant to ether, alcohol and formaldehyde
does uncoating of the adenovirus involve an endosome?
YES
where is adenovirus DNA transcribed?
nucleus
trancribed in two phases
describe the early proteins involved in adenovirus replication
gene regulators
E1A - transcriptional activator
EiB - prevents cell mediated apoptosis via p53
the late proteins are?
structural (capsid) proteins
which enzyme carries out DNA replication?
viral DNA polymerase
when do seasonal adenovirus infections occur?
late winter to early summer
what age group experiences the most adenovirus infections?
6 months to 5 yrs
transmission of adenovirus?
fecal-oral
direct contact
aerosols
ocular shedding
different serotypes of adenoviruses are associated with what infections? (4)
1. endemic respiratory infections
2. epidemic respiratory infection
3. ocular infections
4. gastroenteritis
latent period of adenovirus?
years
replication of adenoviruses occurs where? (2)
1. respiratory tract
2. GI cells
regarding adenovirus
describe acute respiratory disease variant
seen in military recruits
influenza like illness
live oral vaccine (no longer used by army)
describe the pharyngoconjunctival fever variant of adenovirus
children and young adults
transmitted in water
one or both eyes infected
associated with summer camps
describe the epidemic keratoconjunctivitis variant of adenovirus
transmitted by contaminated hands, opthalmic instruments, solutions
one or both eyes can be infected
pain, lacrimation, photophobia
self limited, duration 4-6 weeks, vision unaffected