Respiratory Flashcards
Name a disease that is responsible for reversible airway obstruction.
Asthma.
What intrinsic factors can affect pneumonia?
Cold temperature, infection, stress, exercise, various pollutants.
What can cause acute airway obstruction?
Tumour or foreign bodies with distal collapse of the lung.
What can chronic obstructive pulmonary disease be sub-divided into?
- Chronic bronchitis.
- Emphysema.
Is chronic bronchitis reversible?
Chronic bronchitis is irreversible.
What is the clinical diagnosis of chronic bronchitis?
A persistent cough and sputum for >3 months in 2 consecutive years.
What is the effect of chronic bronchitis on lung function?
- Reduced FEV1/FVC ratio.
- Reduced PEFR.
- Increased TLCO.
What can cause chronic bronchitis?
It is often tobacco smoking induced and can be aggravated by pollution and infections.
What can happen over time in a patient with chronic bronchitis?
The patient might become hypercapnic, hypoxic and have progressive right sided cardiac failure (cor pulmonale) due to pulmonary vasoconstriction. There is fibrosis and tissue destruction.
What is the pathology of emphysema?
Irritants and chemicals trigger inflammatory mediators to release matrix destructive enzymes -> elastin destruction and enlargement of alveolar air spaces -> air trapping.
What can cause emphysema?
It is often tobacco smoking induced. It can also be associated with alpha-1-antitrypsin deficiency and coal dust exposure.
What is bronchiectasis?
Permanent dilation of bronchi due to obstruction and inflammation this leads to a build-up of excess mucus and predisposes someone to chest infections.
What is the effect of interstitial lung disease on lung volumes?
Reduced TCO, VC and FEV1. FEV1/FVC ratio and PEFR is normal.
Give an example of a chronic interstitial lung disease.
Interstitial pneumonia, sarcoidosis, rheumatoid.
What is the pathology of interstitial lung disease?
Increased fibrous tissue within the lung parenchyma resulting in increased stiffness and decreased expansion.
What is the treatment for interstitial lung disease?
Steroids and immunosuppressive agents. Lung transplantation may be required.
Why can drugs be troublesome for some people’s lungs?
Drugs can generate superoxide free radicals which may cause problems.
What is idiopathic pulmonary fibrosis?
Progressive fibrosis in the alveoli that limits the patients ability to respire.
What is the name of the lung disorder group that reflects inhaled dust/toxins?
Pneumoconiosis.
Give an example of a pneumoconiosis?
Coal worker’s pneumoconiosis, silicosis, asbestos exposure, extrinsic allergic alveolitis.
Pneumoconiosis: What is silicosis?
Silicosis often reflects silica exposure and may occur in grinding related occupations and mining practices.
What does someone with silicosis have an increased risk of developing?
TB.
There is a borderline increased risk of cancer.
Pneumoconiosis: What might be the consequences of asbestos exposure?
- Lung cancer.
- Persistent pleural effusion.
- Diffuse pleural fibrosis.
- Diffuse interstitial lung fibrosis.
What might the histological pattern of rheumatoid arthritis in association with lung disease look like?
Rheumatoid arthritis has a pattern paralleling usual interstitial pneumonia (UIP).
If the trachea, bronchi and bronchioles are involved in a disease process, is this likely to be an obstructive or a restrictive disease?
Obstructive.
If the lung parenchyma are involved in a disease process, is this likely to be an obstructive or a restrictive disease?
Restrictive.
If the chest wall is involved in a disease process, is this likely to be an obstructive or a restrictive disease?
Restrictive.
What happens to the FEV1, FVC and FEV1/FVC ratio in an obstructive lung disease?
- FEV1 is < 80% predicted.
- FVC is normal.
- FEV1/FVC ratio < 0.7.
What happens to the FVC and FEV1/FVC ratio in a restrictive lung disease?
- FVC reduced.
- FEV1/FVC ratio normal.
Give an example of a reversible obstructive lung disease.
Asthma.
Give an example of an irreversible obstructive lung disease.
COPD.
What is the affect of COPD on residual volume and total lung capacity?
RV and TLC are increased.
Give an example of a restrictive lung disease.
Pulmonary fibrosis.
How would you describe the PEF for asthma.
Variable.
What factors can commonly exacerbate asthma?
- Cold weather.
- Exertion.
- Fumes.
- Often worse at night.
Define inspiratory reserve volume (IRV).
The additional volume of air that can be forcibly inhaled after a tidal volume inspiration.
Define expiratory reserve volume (ERV).
The additional volume of air that can be forcibly exhaled after a tidal volume expiration.
Define forced vital capacity (FVC).
The maximum volume of air that can be forcibly exhaled after maximal inhalation.
Define total lung capacity.
The vital capacity plus the residual volume. It is the maximum amount the lungs can hold.
Define residual volume (RV).
The volume of air remaining in the lungs after a maximal exhalation.
Define functional residual capacity (FRC).
The volume of air remaining in the lungs after a tidal volume exhalation.
Define tidal volume (TV).
The volume of air moved in and out of the lungs during a normal breath.
Define FEV1.
The volume of air that can be forcibly exhaled in 1 second.
What 2 equations can be used to work out TLC?
- TLC = VC + RV.
- TLC = TV + FRC + IRV.
What is a normal tidal volume?
500ml.
What equation can be used to work out FRC?
FRC = ERV + RV.
Define peak expiratory flow (PEF).
The greatest rate of airflow that can be obtained during forced expiration. Age, sex and height can all affect PEF.
What is the transfer coefficient?
The ability of O2 to diffuse across the alveolar membrane.
How can you find the transfer coefficient?
Low dose CO is inspired, the patient is asked to hold their breath for 10s at TLC, the amount of gas transferred is measured.
Name 3 diseases that might have a low transfer coefficient.
- Emphysema.
- Anaemia.
- Fibrosing alveolitis.
Name a disease that might have a high transfer coefficient.
- Pulmonary haemorrhage.
What is the name of the test that can functionally assess respiratory function?
6 minute walk.
What is consolidation on a CXR?
Regions of the lung filled with liquid e.g. pulmonary oedema. The areas appear white - dense.
What are the possible complications of bronchoscopy?
Pneumonia and pneumothorax.
Give 2 early symptoms and 2 late symptoms of lung cancer.
- Early: change in cough, wheeze, hemoptysis.
- Later: weight loss, lethargy.
If a chronically breathless patient is wheezing, what is the likely cause?
Obstruction.
If a chronically breathless patient is NOT wheezing, what is the likely cause?
Restriction? Are there crackles on auscultation?
Give examples of non-respiratory causes of breathlessness.
Heart disease, anaemia.
Give 3 signs of infection.
- If the patient has a temperature.
- Increased neutrophils.
- Increased CRP.
What is ANCA?
Anti-neutrophil cytoplasmic antibody.
- Auto-immune disorder.
What is the mechanism of ANCA?
ANCA activates neutrophils and monocytes. The neutrophils adhere to endothelial cells, there is degranulation and free radicals are released. The free radicals damage the endothelium. There is further neutrophil recruitment = +ve feedback. This can result in inflammation of the vessel wall - vasculitis.
What disease can be caused by ANCA?
ANCA associated vasculitis.
What are common affects of rheumatoid arthritis on the lung?
- Pleural effusion.
- Fibrosing alveolitis.
- Airway disorders e.g. bronchiolitis and bronchiectasis.
What is Guillain Barre syndrome?
Demyelinating polyneuropathy.
It can present 6 weeks after flu/CMV.
Give 5 types of immune mediated damage.
- Tissue damage in chronic infection.
- Excessive immune response.
- Failure to control immune response.
- On target immune response.
- Off target immune response.
Immune mediated damage: what is the mechanism behind tissue damage in chronic infection?
The infection won’t clear.
There is chronic neutrophil recruitment and persistent cellular activation. Pro-inflammatory mediators are released = tissue damage.
Give an example of a disease where there is tissue damage due to chronic infection.
COPD.
Give examples of diseases where there is an excessive immune response.
- ARDS.
- Asthma.
Give an example of a disease where there is a failure to control the immune response.
Alpha 1 antitrypsin disease: emphysema.
Give an example of a disease where there is an off target immune response.
- AAV.
- Good pasteur’s syndrome.
Name 2 upper respiratory tract infections.
- Common cold: caused by rhinovirus.
- Sore throat: caused by adenoviruses, EBV.
What viruses can cause pneumonia?
Adenoviruses, influenza A and B, measles, VZV.
What are the main antigens on influenza A?
- Hemagglutinin (H).
- Neuraminidase (N).
What is the function of hemagglutinin?
‘Grappling hook’; grabs onto cells.
What is the function of neuraminidase?
‘Bolt cutters’; cuts newly formed virus loose from infected cells.
Which influenza pathogen is commonly behind severe and extensive outbreaks? Why?
Influenza A; it replicates a lot and mutations are common.
Define antigenic drift.
When there are small mutations and minor antigenic variation. Antigenic drift can cause seasonal epidemics.
Define antigenic shift.
When there are larger mutations and major antigenic variation. Antigenic shift can cause pandemics!
How can influenza virus be transmitted?
- Aerosol: coughing and sneezing, inhale particles.
- Droplet: hand to hand.
What is the reproduction number?
The average number of secondary cases generated from a primary case.
Give an example of a disease with a high reproduction number.
Measles.
What is the treatment for influenza?
Supportive care! Antiviral medications might be used to reduce the risk of transmission.
Define outbreak.
> 2 linked cases.
Define epidemic.
More cases in a region/country.
Define pandemic.
Epidemics that span international boundaries.
What are the possible consequences of pandemics?
- High morbidity.
- Excess mortality.
- Social disruption.
- Economic disruption.
What factors are there to suggest that future pandemics may be likely?
- More travel.
- Increasing world population.
- Rise in intensive farming.
What factors are there to suggest that future pandemics may be unlikely?
- Healthier population due to medical advances.
- Better healthcare.
- Vaccination.
- Antivirals.
What can mast cell mediators affect?
Airways and blood vessels. They can result in bronchoconstriction and vasodilation.
Describe the changes in the lung 30 minutes after allergen challenge.
Bronchostriction.
Reduced FEV1.
Describe the changes in the lung 3 hours after allergen challenge.
Vasodilation = increased vascular permeability = inflammation.
Reduced bronchoconstriction.
Upregulated adhesion molecules.
Describe the changes in the lung 6 hours after allergen challenge.
Worsening inflammation, eosinophil involvement. 2nd wave of bronchoconstriction!
How would you describe the airways in asthma?
Hyper-reactive. This leads to inflammation.
What is allergic asthma?
When an innocuous allergen triggers an IgE mediated response. The immune recognition processes are faulty and so there is increased IgE, IL-3,4 and 5 production.
What is non-allergic asthma?
Airway obstruction induced by exercise, cold air and stress.
Describe the process of IgE binding to and activating mast cells.
IgE binds to the high affinity receptor on the mast cell surface. There is cross-linking and biochemical cascades. The mast cells are sensitised and there is degranulation.
What might be released on mast cell degranulation?
- Pre-formed histamine.
- Newly synthesised eicosanoids e.g. cysteinyl leukotrienes (cys LTs) and prostaglandin D2.
- Cytokines e.g. IL-3,4,5.
What is IL-5 responsible for?
Pro-inflammatory and eosinophil survival!
What is IL-3 responsible for?
Increases the number of mast cells.
What is IL-4 responsible for?
IgE synthesis.
Eicosanoid pathway: what enzyme converts phospholipid into arachidonic acid?
Phospholipase A2.
Eicosanoid pathway: what enzyme converts arachidonic acid into leukotrienes?
5 lipoxygenase.
Eicosanoid pathway: what enzyme converts arachidonic acid into prostaglandins?
Cyclooxygenase (COX).
Eicosanoid pathway: what protein inhibits phospholipase A2? What is the advantage of this in asthma?
Lipocortin inhibits phospholipase A2.
This has anti-inflammatory effects as there is reduced arachidonic acid produced and so reduced TXA2 and therefore reduced inflammation!
Which lung mast cell mediators are responsible for bronchoconstriction?
Cys-LTs and histamine.
Briefly describe the eicosanoid pathway.
Phospholipid is converted to arachidonic acid by phospholipase A2. Arachidonic acid can be converted to prostaglandins by COX or to leukotrienes by 5 lipoxygenase.
Which lung mast cell mediators are responsible for inflammation?
Cys-LTs, histamine and cytokines.
Which lung mast cell mediators are responsible for airway remodelling?
Cys-LTs, cytokines and enzymes.
Give 3 reasons why the airways hyper-reactive in asthmatics?
- Inflammatory infiltrate.
- Eosinophils.
- Epithelium destruction gives easier access to bronchoconstrictors.
What is the mechanism behind hyper-reactivity?
Neurogenic inflammation.
Describe neurogenic inflammation.
Sensory nerve activation initiates impulses. The impulses stimulate CGRP. CGRP is pro-inflammatory, it activates mast cells and innervates goblet cells.
What are the 3 main functions of CGRP in neurogenic inflammation?
- Pro-inflammatory.
- Mast cell activation -> mediator release.
- Innervation of goblet cells -> mucous release.
What are the 2 principles of asthma treatment?
- Alleviate symptoms.
- Target inflammation.
What broad class of drugs are commonly used to alleviate symptoms?
Bronchodilators.
What broad class of drugs are commonly used to target inflammation?
Steroids.
Name 3 types of bronchodilators that are commonly used.
- Beta agonists.
- Muscarinic antagonists.
- Methylxanthines.
What makes LABA long acting?
They have increased lipophilicity.
What type of beta adrenergic receptors are found in the lungs?
Beta 2.
Where are beta 1 adrenergic receptors found?
In the heart.
Where are beta 3 adrenergic receptors found?
In adipose tissue.
Describe the process of PKA synthesis from beta 2 receptor activation.
Beta 2 interacts with Gs. This activates adenylate cyclase. Adenylate cyclase converts ATP to cyclic AMP, this then leads to PKA synthesis -> bronchodilation.
Give 2 functions of cAMP.
- Stabilisation of mast cells, inhibits mast cell mediator release.
- Relaxes airway smooth muscle.
What happens following activation of the M3 receptor?
M3 interacts with Gq. Phospholipase C is activated, this leads to DAG and IP3 production which further leads onto Ca2+ and PKC production.
How do muscarinic antagonists work?
They prevent M3 receptor activation and so there is a reduction in Ca2+ activation. This means less MLC kinase is produced and you have reduced muscle contraction.
How do methylxanthines work?
They are PDE inhibitors. They increase cAMP production and therefore PKA production. PKA inhibits MLC kinase and you have reduced muscle contraction.
Where is PDE4 found?
In the airways and inflammatory cells.
Which physiological process can explain how bronchodilators work?
Myosin light chain.
What is the function of MLC kinase?
MLC kinase phosphorylates MLC which causes muscle contraction.
What inhibits MLC kinase?
PKA.
(PKA is produced from cAMP).
What activates MLC kinase?
Calmodium.
(Calmodium is produced from Ca2+).
Using the myosin light chain, explain how beta agonists and methyxanthines work to alleviate symptoms.
Beta agonists and methylxanthines result in increased cAMP and therefor PKA. MLC kinase is inhibited and you have less smooth muscle contraction in the airway -> bronchodilation.
Using the myosin light chain, explain how muscarinic antagonists work to alleviate symptoms.
Muscarinic antagonists block M3 receptor activation and so you have a reduction in Ca2+ production. Less MLC is activated and so you have less smooth muscle contraction in the airway -> bronchodilation.
Where are anti-inflammatory steroids produced?
Adrenal cortex.
Where in the adrenal cortex are mineralocorticoids produced and give an example of one.
- Zona glomerulosa.
- Aldosterone.
Where in the adrenal cortex are glucocorticoids produced and give an example of one.
- Zona fasciculata.
- Hydrocortisone.
How do glucocorticoids work?
They interfere with gene transcription.
Give 2 effects of hydrocortisone.
- Metabolic.
- Anti-inflammatory.
Give 3 potential side effects of prolonged hydrocortisone use.
- Muscle wasting.
- Osteoporosis.
- Increased risk of infection.
What receptor has ‘zinc fingers’?
The glucocorticoid receptor.
What are the main cells responsible for inflammation in asthma?
Mast cells and eosinophils.
What are the main cells responsible for inflammation in COPD?
Neutrophils and macrophages.
Effects of steroids: what is the effect of a positive GRE?
Positive GRE = increased transcription. There is also increased lipocortin production - this is anti-inflammatory as it inhibits phospholipase A2.
Effects of steroids: what is the effect of a negative GRE?
Negative GRE = suppression of cytokines.
Describe the mechanism behind aspirin induced asthma.
Aspirin inhibits COX. There is an increase in arachidonic acid. This is shunted and there is increased leukotriene production = INFLAMMATION!
How does anti IgE therapy work?
Ab binds to and neutralises free IgE; this prevents IgE binding and results in decreased mast cell sensitisation. Allergens are unable to activate mast cells.
What is the advantage of having inhaled medications in the management of asthma?
Inhaled medications are more likely to reach the target sites and there is reduced chance of side effects.
Name 5 groups of people who might be at increased risk on pneumonia.
- The elderly.
- Children.
- People with COPD.
- Immunocompromised people.
- Nursing home residents.
Describe in 3 steps the pathogenesis of pneumonia.
- Bacteria translocate to normally sterile distal airway.
- Resident host defence is overwhelmed.
- Macrophages, chemokines and neutrophils produce an inflammatory response.
What can cause pneumonia to be severe?
- Excessive inflammation.
- Lung injury.
- Resolution failure.
Describe the process of pneumonia resolution?
Bacteria are cleared and inflammatory cells are removed by apoptosis.
What protective features does the respiratory tract have against pathogens?
Teeth, commensal bacteria, swallowing reflex - epiglottis closes respiratory tract, mucociliary escalator, coughing and sneezing etc.
What symptoms might you see in someone with pneumonia?
- Productive cough.
- Sweats.
- Fever.
- Breathlessness.
- Pleuritic chest pain.
- Myalgia, headache, arthralgia suggests atypical pneumonia.
What signs might you see in someone with pneumonia?
- Fever.
- Signs of lung consolidation - bronchial breath sounds and dull to percuss.
- Pleural effusion - stony dull percussion.
- Crackles and wheeze.
- Abnormal vital signs.
What investigations might you do on someone to determine whether or not they have pneumonia?
- CXR - look for air bronchogram in consolidated area.
- FBC (look at WBC’s).
- U+E.
- Liver function tests.
- CRP (marker of inflammation).
- Microbiology: sputum culture, blood culture, serology etc.
How can pneumonia be prevented?
- Children are given PCV.
- Smoking cessation is encouraged.
- Influenza vaccines are given to children and the elderly.
What is CURB65 used for?
It is a way of assessing the severity of community acquired pneumonia. It predicts mortality.
What does CURB65 stand for?
Confusion.
Urea >7mmol/L.
RR >30/min.
BP reduced - systolic <90mmHg, diastolic <60mmHg.
Age >65.
Why is CRB65 often used in the community?
Because facilities to measure urea are often not available.
Name 2 bacteria that are common causes of pneumonia?
- Streptococcus pneumoniae.
- Haemophilus influenzae.
Describe s.pneumoniae.
Gram positive cocci chain. Alpha haemolytic and optochin sensitive.
Describe haemophilus influenzae.
Gram negative bacilli.
What antibiotic would you give to someone with haemophilus influenzae?
Co-amoxiclav or doxycycline.
What groups of people may develop pneumonia caused by klebsiella pneumoniae?
- Homeless people.
- Alcoholics.
- People in hospital.
What kind of bacteria is klebsiella pneumoniae?
Gram negative bacilli.
What can be a sign of effusion on a CXR?
Lots of consolidation.
What is empyema?
Pockets of pus that have collected in a body cavity e.g. in the lungs.
Give 3 signs of empyema.
- WBC/CRP don’t settle with antibiotics.
- Pain on deep inspiration.
- Pleural collection.
What is the usual treatment for empyema?
Drainage.
Name 3 groups of people who might be at risk of hospital acquired pneumonia.
- Elderly.
- Ventilator associated.
- Post operative patients.
What is bronchiolitis?
Airway obstruction caused by inflammation of the bronchioles and increased mucus secretions. It is caused by RSV infection.
What can cause bronchiolitis?
Respiratory syncytial virus (RSV).
In what group of people is bronchiolitis common?
Children.
What is the difference between bronchitis and bronchiolitis?
- Bronchiolitis: inflammation of bronchioles and increased mucus secretion due to RSV infection.
- Bronchitis: inflammation of bronchi epithelium due to irritants and chemicals.
What investigations might you do in someone you suspect to have infective bronchitis?
- CXR (often normal).
- Viral and bacterial swabs.
What is the usual cause of infective bronchitis?
- Mainly viral!
- Acute bronchitis can be caused by adenoviruses.
Is infective bronchitis normally caused by bacterial or viral infection?
Viral.
Is pharyngitis normally caused by bacterial or viral infection?
Viral e.g. rhinovirus, adenovirus etc.
What bacteria might sometimes cause pharyngitis?
Streptococcus pyogenes.
What is the Centor criteria used for?
It determines the likelihood that a sore throat is bacterial.
What signs make up the Centor criteria?
- Tonsillar exudate.
- Tender/enlarged anterior cervical lymph nodes.
- Fever (>38°C).
- Absence of cough.
(3 or 4 of these = 50% chance of bacterial infection).
Is sinusitis usually bacterial or viral?
Viral.
What type of bacteria is Bordetella pertussis?
Gram negative bacilli.
What are the symptoms of whooping cough in adults?
- Chronic cough.
- Inspiratory ‘whoop’ posttussive vomiting.
What agar would you culture bordetella pertussis on?
Bordet Gengou agar.
What antibiotics might you use in someone with bordetella pertussis infection?
Clarithromyocin.
When is someone vaccinated against bordatella pertussis?
A child is vaccinated at 8, 12 and 16 weeks and at 3 years 4 months with dTaP vaccine.
What causes Croup?
Parainfluenza virus.
In which group of people is Croup common?
Children.
What is croup?
Acute larygnotracheobronchitis - trachea, bronchi and larynx are all affected.
Malignant bronchial tumours can be divided into two groups; what are they?
- Non small cell cancer.
- Small cell cancer.
Which type of malignant bronchial tumour fits into TNM staging?
Non small cell cancer.
Which type of malignant bronchial tumour tends to have a worse prognosis?
Small cell cancer.