resp Flashcards
alveolar macrophages - features + function
where do they go
- main feature: live in the alveoli - outside the body!
- > eat particles that didnt get trapped by mucous
either move up mucociliary escalator; or move back through into alveolar wall and stay there till death
Alveolar-capillary membrane
- thickness
- surface area
- alveolar volume
- capillary volume
- 0.5 micron
- 50-100m2
- 3-6 L
- 80mL (increases with increased CO)
around how many dichotomous branchings are there in the lungs?
23
At what level do bronchioles start
around 10-15th dichotomous branch
Clinical signs of acute pneumonia? (11)
Relatively well; then acutely ill
- resolves by crisis
signs:
- abrupt onset
- unrelenting cough
- lots of sputum
- fever
- raised WBC
- pleuritic chest pain
- sputum may be blood-stained
- G+ diplococci in sputum
- bacteraemia
- consolidation
- bronchial breathing
Clinical signs of atypical (interstitial) pneumonia (5)
“flu-like”
- symptoms are symptomatic and not as debilitating
- “walking pneumonia” - slower onset; cough a long time
- malaise
- headache
- diarrhoea
- aches; pains
- dry cough
Common cold - is lab diagnosis necessary?
- treatment
unnecessary
supportive treatment
componets of blood-gas barrier
lung: surfactant; type 1 pneumocyte; basal lamina connective tissue
capillary: basal lamina; endothelial cell; plasma
(sometimes basemet membranes are fused and there is no connective tissue)
Crepitations indicate pathology of which site(s) in the lungs?
what is the best test for this area?
terminal lung units - alveoli; parenchyma; interstitium
best test - ct scan (CXR will show gross abnormality)
croup (LTB)
- is lab diagnosis necessary?
- treatment
seldom necessary - clinical diagnosis and usually viral
if severe - inhaled steroids; otherwise no treatment
Definition of asthma
- 2 word
- longer
2 word: reversible bronchoconstriction
longer: increased responsiveness of airways to various stimuli; leading to episodic bronchoconstriction which is at least partially reversible
epiglottitis
- is lab diagnosis necessary?
- treatment
yes - whenever possible
-> be careful - irritation of the area -> inflammation -> closed off airways
treatment
- essential
- always bacterial
- very severe
features of type I pneumocytes - predominance (how much surface area they take up) - function - what are the junctions between cells and basal lamina - can they reproduce
95% of surface area gas exchange tight junctions - prevent leak of ECF into alveoli; basal lamina is thick and prominent - no - die and must be replaced (by type II)
features of type II pneumocytes - how much surface area do they take up? - function - structure - features - can they reproduce
- 5% (though more numerous than type I) - secrete surfactant - cuboidal cells - short microvilli + lamellar bodies that contain surfactant - yes - divide and give rise to both type I and II pneumocytes
How do antibodies neutralise influenza virus?
influenza - binds receptors via receptor-binding site on HA - receptor binding site - surrounded by 5x antigenic sites - antibody binds to one of these -> sterically inhibits binding of HA to receptor (ab is similar size to HA)
How does antigenic drift occur in influenza? in epidemics?
- mutations in antigenic sites are selected for if they prevent the binding of antibodies - antigenic drift = mutation + selection mutation: error of replication of viral RNA-dependent RNA polymerase epidemic - change in all 5 sites - point mutations - or reassortment -> swapping of gene segments on co-infection of a single cell -> get totally different HA/NA (problem: avian have specificity for a2-3 binding; and we have receptors with a2-6 -> but if avian + human co-infect a mixing vessel - eg pig - then we could have recombination such that genes are adapted for human growth; but HA and NA are avian. then there is mutation + selection for a2-6 specificity)
How does consolidation in lobar pneumonia spread through the lung?
Moves through pores between alveoli - get the whole lobe
How does diffusion limitation of oxygen occur in high-altitude environment?
High altitude - have lower atmospheric PO2 -> the gradient between partial pressures is lower -> have slower diffusion across membrane https://onenote.officeapps.live.com/o/GetImage.ashx?Fi=SDFD3144C4D713EDE3%21370&C=1__BAY-SKY-WAC-WSHI&ak=m%3Den%2Dau&ObjectDataBlobId=%7B52701cc9-9860-8048-b1c5-cc06599fc06b%7D%7B1%7D&usid=8e68f0f2-010c-446e-b7c9-63d80c9d17ee&build=16.0.2430.1026 also - the rate of rise of PO2 for a given increase in blood O2 is lessened - steep slope of O2 dissociation curve when PO2 is low => exercise may result in diffusion impairment of O2
how does influenza spread between people?
droplet infection - coughing; sneezing doesn’t spread too far (cf measles)
How does the pulmonary system maintain low P when CO increases?
- recruitment of pulmonary vessels that are not normally perfused - dilatation of vessels
How many subtypes of influenza A and B are there?
B - no subtypes A - subtypes according to which HA; NA combo it has - HA1-17 - NA1-10
If there are signs that abnormality is respiratory; but the chest sounds clear - what could this indicate? examples?
pathology is VASCULAR ** - PE - infarct can irritate pleura (pleuritic pain); cause haemoptysis; but chest sounds clear - pulmonary hypertension; pulmonary vasculitis -r are
Influenza virus - family - genome structure - envelope? what are the different types?
- Orthomyxoviridae family - genome: segmented ssRNA; -ve sense; arranged as 8 RNP’s RNP = ribonucleoprotein (genome wrapped in helix; nucleoproteins; attached RNA-dependent RNA polymerase) - enveloped 3 types - A; B; C - structurally similar; but no immunological cross-reactivity - only A and B are major human pathogens - A can also infect other species
Influenza: ion channel blockers - name drugs - influenza A or B? - how does it work? - administration - populations
- adamantanes - amantadine; rimantadine - only A - blocks M2 ion channel - no acidification of virus interior; RNP’s remain fused to matrix - oral; daily - children; prophylactic in nursing homes - but developing drug resistance so used rarely
Influenza: NA inhibitors - name drugs - influenza A or B? - how does it work? - administration - populations
- relenza (zanamivir); tamiflu (oseltamivir) - both A and B - blocks NA -> virus can’t cleave sialic acid; clumps around release site as HA binds receptor - both 2x daily - relenza: inhalation by mouth; tamiflu: oral - all ppopulations -but circulating H1N1 strains are showing resistance to tamiflu
Interesting features in 1918-1919 flu pandemic
25-30% of human population clinically infected; 20-50million deaths deaths unusually high in 15-35 age group; often rapid symptoms: pulmonary oedema; haemorrhage; cyanosis
Interesting features of avian H5N1 flu
- HA has a different cleavage site- can be cleaved by enzymes in any cell in body -> systemic infection - kills rapidly - highly lethal (~60%) - so far no jump human to human - susceptible to NA inhibitors - but need to get them quickly
Interesting features of swine-origin H1N1
- greater ability to replicate in lungs than seasonal flu - some health; young adults getting viral pneumonia - death in younger people
Lung volumes
https://onenote.officeapps.live.com/o/GetImage.ashx?Fi=SDFD3144C4D713EDE3%21370&C=1__BAY-SKY-WAC-WSHI&ak=m%3Den%2Dau&ObjectDataBlobId=%7B6bf1b254-cfc1-42b2-a1bc-da5366896ab7%7D%7B1%7D&usid=8e68f0f2-010c-446e-b7c9-63d80c9d17ee&build=16.0.2430.1026
On what basis is diagnosis of asthma made? clinical/physiological/histological…?
clinical + physiological evidence histology: features on biopsy are largely non-specific
otitis media
- is lab diagnosis necessary?
- treatment
lab diagnosis - seldom necessary (know is normal commensal bacteria)
(can aspirate fluid from middle ear
treatment: antibiotics if: 48hrs) and severe
- generally children do better w/out antibiotics
Pathogenesis of the common cold (applies to most URT viruses)
virus enters airway virus adsorved onto respiratory epithelium virus replicates in epithelial cells virus shedds - clear fluid outpours from lamina propria (runny nose) - cell damage - infection spreads host defences are activated secondary infection by bacterial commensals - epithelium and cilia have been damaged - overgrowth of commensals - fluid becomes purulent then recovery - clearing of bact/virus by interferon and antibodies; regeneration of epithelium
pharyngitis/tonsillitis - is lab diagnosis necessary? - treatment
lab diagnosis if possible (kit - swab back of throat - look for grp A strep antigens) can’t clinically diagnose if bacterial or viral treat with antibiotics if bacterial; otherwise supportive
pleural histology
parietal pleura: mesothelium; supported by basal lamina and fibrous connective tissue visceral pleura: have microvilli on surface - can trap hyaluronic acid for lubrication; but is conduit for bugs
sinusitis - is lab diagnosis necessary? - treatment
seldom necessary - can see fluid in cxr if need be; or ent surgeon can aspirate fluid treatment: if bacterial and severe - antibiotics otherwise - supportive
Steps in pathogenesis of influenza? what causes pathology? consequences of infection
Pathogenesis: 1. droplets containing virus enter respiratory tract 2. virus binds to sialic acid-containing receptors on non-ciliated respiratory epithelium3. Virus replicates in epithelial cells of upper and lower respiratory tract; particularly in large airways Pathology: tissue damage and inflammatory response -> local symptoms cytokines; interferon [DC and macrophages] -> fever (IL-1); malaise; head and muscle aches (IFN) Consequences:- Acute infection - in immunocompetent individuals; the pre-existing and developing immunity is sufficient to clear virus - in some; viral replication occurs in lung parenchyma -> primary viral pneumonia- secondary bacterial infection - viral replication may occur in ciliated epithelium of trachea/bronchi - destruction of cilia - allows commensals to invade lower down
Steps in replication cycle of influenza (10)
- Viral HA binds sialic acid-containing receptor on surface of respiratory epithelial cell 2. Virus taken in by receptor-mediated endocytosis 3. Endosome becomes acidic; HA changes (because has been cleaved by trypsin Clara previous) and hydrophobic region is exposed - fusion of viral envelope + endosomal membrane 4. Viral RNPs are released - M2 ion channel has acidified environment inside virus - releases RNPs (bound to matrix protein) - RNPs enter nucleus 5. Viral RNA amplification; production of mRNA 6. Viran NPs and proteins are synthesised in cytoplasm; shunted back to nucleus; combine with RNA => RNPs are formed 7. HA and NA are also formed; glycosylated in ER and golgi; and deposited onto cell surface 8. Biruses bud out of cell - RNP’s acquire surface glycoproteins and envelope 9. NA cuts salic acid receptors from cell surface -> allows budding viruses to move away from cell 10. Virus HA is cleaved by tryptase Clara outside cell -> becomes infectious
structure of alveoli: - what type of epithelium? - what is bw alveoli?
epithelium: simple squamous intra-alveolar septum between alveoli - pores (allow air to equilibrate bw alveoli) - reticular + elastin fibres - keep alveoli open
structure of bronchiole
- have slightly changed respiratory epithelium (progressive loss of goblet + ciliated cells; gain in Clara cells) - still have smooth muscle - but no cartilage
structure of respiratory bronchioles
- epithelium: cuboidal -> squamous - have intermittent alveoli -> eventually just peter out and become wall-to-wall alveoli
Target populations for influenza vaccine
> 65 yo immunocompromised health workers diabetes; cancer chronic lung; heart; kidney disease
Termial bronchiole structure
- epithelim: no goblet cells; clara cells + cuboidal epithelium with some cilia - and 1-2 layers of smooth muscle
trachea - histology - what are the 3 layers - what is defining histology of trachea?
mucosa (resp epithelium) submucosa (glandular) adventitia (cartilage + CT) - defining: C-shaped hyaline cartilage
Upper respiratory microbiota - aerobic or anaerobic?
both - significant amounts of anaerobobic in nasal washings; saliva; tooth surfaces; gingival scrapings
What % of people typically are infected with influenza each year in Australia?
10-20% of population
What 3 groups of microbes cause pneumonia? Examples of each when they cause disease
- URT flora - normal commensals - S. pneumoniae; H. influenzae; Staph aureus - cause disease when host immune system is compromised 2. Enteric saprophytes - E. coli; Pseudomonas - see in hospitalised patients - cause pneumonia by contaminating airways; or via blood 3. Extraneous pathogens - floating in environment - Legionella phenumophilia; tuberculosis
what are 3 obstructive lung diseases
asthma
COPD (emphysema; chronic bronchitis; small airways disease)
bronchiectasis
what are 4 restrictive lung disease
idiopathic pulmonary fibrosis
pneumoconiosis -
asbestosis
sarcoidosis “honeycomb lung”
What are 4 ways that pathogens enter the lower respiratory tract?
- inhalation of pathogens - air droplets 2. aspirations of infected secretions from URTI 3. aspiration of infected particles - gastric contents; food; drink; foreign bodies 4. haematogenous spread
what are clara cells? where are they found and why are they importat in that location? what other fuctions do they have?
columnar-cuboidal cells with short microvilli secrete surfactant found lower down in bronchioles - important there because it is wet and sticky; but there is no cartilage - surfactant neeeded to keep them open also have glycoprotin granules; and may neutralise toxins
what are components of load of respiratory work
stiff lungs narrow airways chest wall diaphragm
What are microbial causes of acute exacerbations of chronic bronchitis? (2)
pneumococci and/or H. influenzae -> commensals
What are some airways diseases that cause dyspnoea
upper airways - tumour; foreign body; croup
lower airways - asthma; COPD; bronchitis
what are some alveolar diseases that cause SOB (4)
pneumonia;
lung collapse;
pulmonary oedema;
pulmonary fibrosis
What are some common causes of croup (LTB) (3) usually viral or bacterial?
viral parainfluenza virus influenza A RSV
What are some common causes of laryngitis? (3) usually bacterial or viral?
usually viral - some bact parainfluenza virus influenza H. influenzae
What are some common causes of pharyngitis/tonsillitis with nasal involvement? (5) usually bacterial or viral?
usually viral; maybe bacterial enterovirus adenovirus influenza reovirus s.pyogenes - group A; C; G
What are some common causes of pharyngitis/tonsillitis without nasal involvement (4) usually viral or bact?
usually viral parainfluenza virus enterovirus adenovirus influenza
What are some common causes of primary sinusitis? viral or bacterial?
usually part of common cold syndrome -> viral
What are some common causes of secondary sinusitis? (2) usually bacterial or viral?
usually bacterial involvement due to decreased immunity (after common cold etc) s. pneumoniae - commensal H. influenzae - commensal
What are some common causes of the common cold syndrome (7) usually bacterial or viral?
usually viral rhinovirus parainfluenza virus enterovirus (in summer) influenza coronavirus HMPV - human metapneumovirus RSV
What are some complications of pneumonia?
acute lobar: - pleural fibrosis -> pleuritis - empyema - collection of pus in pleura; walled off by fibrosis bronchopneum: - abscess atypical: - bronchiectasis - interstitial fibrosis - cystis
What are some microbiota found in latent state in some healthy people? - in lung (2) - in lymph nodes; sensory nerves (3)
P. jirovecii carinii M. tuberculosis sensory/lymph - CMV - HSV - EBV
what are some pleural/chest wall diseases that cause SOB (3)
pleural effusion;
pneumothorax;
chest wall deformity
what are some pulmonary vascular diseases that cause dyspnoea
PE; vasculitis; primary pulmonary hypertension
what are some resp muscle diseases that cause SOB (2)
resp muscle weakness;
phrenic nerve palsy
What are some risk factors for different pathogens in pneumonia?
Occupation - contact wiht animals - Chlamydophyla (birds) - hides - anthrax - air conditioning - C. pneumophilia; Legionella - soils - Legionella longbechea Travel - diff species Homelessness - mycobacteria - alcoholism - Klebsiella
What are some specimen types for lab analysis of pneumonia?
- sputum (must be properly collected; not contaminated by URT flora) - transtracheal aspirate - aspiration via tracheostomy; endotracheal tube; bronchoscope - pleural tap - lung biopsy - blood - culture and serology
What are some URT microbes that are carried in 1-10% of healthy people? (2)
Strep. pyogenes meningococci (Neisseria)
What are some URT microbes that are carried in >50% of all people (7)
viridans streptococci (common source of endocarditis - after dental work) Neisseria spp (low grade Neisserias) Corynebacterium spp G- anaerobes H. influenzae (not type B) C. albicans S. pneumoniae (in 15-85%) - tend to be the less pathogenic serotypes
What are some URT microbiota that are carried in <1% of healthy people (uncommon) (3)
Enterobacteria Pseudomonas C. diphtheriae
What are the 3 other cell types found in respiratory epithelium (other than ciliated columnar; basal stem cells; goblet cells)
brush cells with microvilli - maybe sensory? serous cells - secretory small granule cells - endocrine
