Respiration Flashcards
effect of removal on breathing
cortex and pons: slow gasping breaths
medulla: breathing stops
expiratory neurons
inhibit inspiratory neurones.
inspiratory neurones activate expiratory neurones
lung receptors
c fibre endings, afferent nerve fibres carried in vagus
chemoreceptors
central = fast response to arterial pO2 on surface of medulla , arterial pCO2, arterial {H+} and peripheral pCO2
Slowly Adapting Receptors (SARs)
aka stretch receptors, mechanoreceptors situated close to airway smooth muscle, stimulated by stretching of airway walls during inspiration, help inititate expiration and prevent overinflation. afferent fibres= myelinated
rapidly adapting receptors (RARs)
aka irritant receptors, located airway epitheloim, respond to rapid inflation, smoke, dust , RARs in trachea initiate cough, mucus, bronchocontricition
myelinated
C-fibre endings
unmyelinated nerve endings, stimulated by increased interstitial fluid (oedema) and inflammatory mediators
hypoxia and co2 buildup
common in copd patients, leads to chronic hypercapnia, loss of sensitivity of central chemoreceptors. ig given o2 abolishes drive to breathe as has become controlled by hypoxia
drug respiratory depressants
anaesthetics, opiod analgesics, sedatives
drug respiratoy stumlants
doxapram, b2 agonsits aka bronchodilators
regulation of breathinh
Midbrain neural activity stimulates breathing during
wakefulness (“wakefulness drive to breathe”)
During sleep:
• Respiratory drive decreases (loss of wakefulness drive)
– reduction in metabolic rate
– reduced input from higher centres such as pons and cortex
upper airway muscle activity
phasic: contraction of upper airway muscles, opening of upper airway, facilitates inward flow
tonic: continous background activity, maintains airway
during sleep loss of tonic activity
apnoea= cessation of breathing
obstructive sleep apnoea
important cause of rtcs
rfs: obesity, alcohol, nasal obstruction `
respiratory rhythm originates in medulla
hypoxia and hypercapnia feedback via chemoreceptors
elastic recoil
lung= inward
chest wall= outward
inspiration
alveolar pressure
expiration
Alveolar pressure > atmospheric
what causes SOBOE in COPD
decreased lung elastic recoil
obstruction, inability to increase tidal volume effectively
inspiration is active
expiration is passive ( recoil)
breathing disrupted by
airflow obstruction - copd and asthma
weakness of expiratory muscles (MND. advanced respiratory disease, diaphragm failure)
lung tissue damage (emphysema)
thoracis cage disorders ( ankylosing spondylitis, kyphoscoliosis)
dalton’s LAW
gases in a mixture exert pressures that are independant of each other
henry’s law
the concentration o a fissolved gas is dirctly proportional to its partial pressure
nitrogen in blood
high atmospheric content, low water solublility, under high pressure has an anasthetic effect, nitrogen narcosis, on reduction of pressure N2 emboli cause local ischaemia - bends
2,3 -bisphosphoglcerate
binds to deoxy-Hb and lowers Hb affinity for o2 imroving o2 delivery to tu=issues
foetal Hb has a lower affinity for 2,3 BPG so has a higher oxygen affinity than Hba
Haemoglobin
A tetramer: 2 alpha and 2 beta subunits
Each subunit has a Haem group
• A porphyrin with a central Ferrous atom: binds O2
• Combines loosely with Oxygen
• Combination alters its shape and charge
Oxygen/Hb Dissociation
The affinity of binding O2 increases with each successively bound O2
molecule: Allosteric Effect
• Once bound a number of factors can change the ability of Hb to take
up and liberate oxygens
• Ultimately we want Hb to take up O2 in the lung and liberate O2 at
the tissues (muscles)
in practice
nearly all the oxygen carried in the blood is bound to haemoglobin
Partial pressure of oxygen PO2
kPa
Gas exchange is driven by partial pressure • Partial pressure of oxygen in the alveolus equals the partial pressure in the blood draining the alveolu The partial pressure of oxygen in mixed alveolar gas is higher than that of arterial blood • This is due to shunting
shunting
To move something from one place to another, usually because that thing is not wanted, without considering any unpleasant effects Anatomical shunts • A small amount of arterial blood doesn’t come from the lung (Thebesian veins) • A small amount of blood goes through without seeing gas (bronchial circulation) • Physiological shunts (V) and alveolar dead space (Q) • Not all lung units have the same ratio of ventilation (V) to blood flow (Q) • V/Q mismatch
Summary
Gas exchange allows oxygen into blood and CO2 out
• The passage of oxygen to the blood is by diffusion
• The carriage of oxygen is mainly performed by Hb
• The level of oxygen in the blood is roughly the same as that in the
alveolus in health
What causes a low level of oxygen in the blood?
Hypoventilation
• Hypoventilation allows less air (and oxygen) to enter the alveoli so
less oxygen available to the blood
• Decreased environmental oxygen e.g. altitude
• A problem with the alveolar/capillary membrane
• Miss-match of ventilation and perfusion (next lecture)
What can increase the partial pressure of oxygen?
Hyperventilation
• Administration of oxygen
Increase in available PO2
in healthy state
• At a normal PO2
, blood carries nearly as much oxygen as it
possibly can
• Therefore increasing the PO2 has very little effect on the
oxygen content
• However in disease oxygen therapy is a key intervention
CO2 changes dynamically with hyper and
hypoventilation
whilst o2 stays fairly constant
Normal” V/Q mismatch
• Less airflow and blood flow at the top of the lung but V>Q = high V/Q • Middle of lung V/Q normal • Bottom of lung more ventilation and more blood flow but V
Increased V/Q Ratio
Lots of ventilation to alveoli, not much blood • Alveoli and blood reach an equilibrium which is closer to air • PO2 is therefore higher • (and PCO2 is lower)`
Low V/Q ratio
Less ventilation to alveoli, lots of blood • Alveoli and blood reach an equilibrium which is closer to venous blood • PO2 is therefore lower (and PCO2 is higher)
Physiological Dead Space
Physiological Dead Space
V/Q mismatch
Calculate the expected alveolar PO2 (PAO2 ) using the alveolar gas equation • Compare with the measured arterial PO2 (PaO2 ) • If PAO2 = PaO2 then no mismatch
A-a Gradient
Tells us the difference between alveolar and arterial oxygen level • Can help to diagnose the cause of hypoxaemia • High A-a gradient • Problem with gas diffusion • V/Q mismatch • Right to left shunt
CO2 is mostly dissolved in blood
o2 bound to hb
Won’t breathe: control failure
Brain failure to command e.g. drug overdose
Can’t breathe: broken peripheral mechanism
- Nerves not working e.g. phrenic nerve palsy
- Muscles not working e.g. muscular dystrophy
- Chest can’t move e.g. severe scoliosis
- Gas can’t get in and out e.g. asthma/COPD
Type 2 respiratory failure
Decrease in PO2 • Increase in PCO2 • Common causes in hospital: • Severe COPD (can be acute or chronic) • Acute Severe Asthma • Pulmonary Oedema in acute Left Ventricular failure • Due to hypoventilation as main feature
Give oxygen
• Controlled in COPD patients with chronic respiratory failure
• Treat the underlying cause to reverse hypoventilation e.g.
bronchodilators for acute asthma or opiate antagonists for overdoses
• Support ventilation
• Non-invasive ventilation
• Invasive ventilation
What causes V/Q mismatch?
Most lung diseases effecting the airways and parenchyma • Lung infection such as pneumonia • Bronchial narrowing such as asthma and COPD (although they can also progress to type 2 resp failure) • Interstitial lung disease • Acute lung injury (COVID) Pneumonia causes mismatch
What happens to arterial CO2 in V/Q mismatch?
• Blood leaving areas of low V/Q ratio has
• Low PaO2
• High PaCO2
• High PaCO2 stimulates ventilation
• ‘Extra’ ventilation goes to areas of normal
lung and areas with high V/Q ratio so get
blood with low CO2
• Blood from both areas mixes so overall
CO2
is normal
What happens to arterial O2 In V/Q mismatch
• Blood leaving areas of low V/Q ratio has • Low PaO2 • High PaCO2 • High PaCO2 stimulates ventilation • ‘Extra’ ventilation goes to areas of normal lung and areas with high V/Q ratio • But extra ventilation can’t push O2 content much higher than normal • Blood from both areas mixes but cannot overcome the low oxygen level
How do we treat respiratory failure
Give Oxygen
• Treat the underlying cause
V/Q mismatch due to perfusion
problems
Pulmonary embolism
• Can range form small PTE causing no problem with gas exchange
ranging to massive PE with hypoxia
• Emboli effectively cause areas of dead space where there is
ventilation but no perfusion causing hypoxia
• Massive emboli can cause circulatory failure and death
Treatment of Pulmonary Emboli
Oxygen in acute episode
• Anticoagulation to stop further clot propagation
• Thrombolysis in some cases where circulatory compromise
Asthma and Respiratory Failure
Hypoxaemia suggests significant asthma attack • Bronchospasm and mucous plugging causes ventilation defects and V/Q miss match • Type 2 resp failure develops when severe bronchospasm causes hypoventilation of alveoli or exhaustion • The patient needs oxygen to survive • Invasive ventilation may be required
COPD and Respiratory Failure
• COPD is a mixture of chronic airways inflammation and narrowing and emphysema • Problems with V/Q mismatch and hypoventilation • May present acutely with respiratory failure type 1 or type 2 • May have chronic type 2 respiratory failure in advanced disease • Treat respiratory failure with oxygen but with caution in chronic type 2 respiratory failure
Masks
Variable performance • Cheap and cheerful • Exact inspired O2 concentration not known • Fixed function • Constant, known inspired concentration • Reservoir mask • High inspired concentration of O2 Controlled oxygen therapy: Venturi Mask`
How do we quantify oxygen carriage?
Haemoglobin saturation • Because it’s very easy to do! • Assuming Hb is normal, it’s an accurate reflection of oxygen content 2. Arterial blood gases • More complicated and invasive • PaO2 reflects haemoglobin saturation but is a measure of the partial pressure of O2 in the blood
Carbon monoxide poisoning
Carbon monoxide binds to haemoglobin in the place of oxygen to
form carboxyhaemoglobin
• (also interfers with mitochondrial respiration)
• Death by asphyxia
• Treatment is high concentration oxygen (to displace the CO from the
haemoglobin)
Type 1 Respiratory Failure
Low PaO2 • Normal (or low) CO2 • Caused by V/Q mismatch decreasing adequate gas exchange • e.g. Pneumonia Lung diseases effecting the parenchyma • Interstitial lung disease • Bronchiectasis • Obstructive airways disease e.g. asthma and COPD (but these can also cause type 2 RF) • Pulmonary embolism • Treat with oxygen whilst treating underlying cause
Type 2 Respiratory Failure
• Low PaO2 • High PaCO2 • Caused by hypoventilation • May be acute or chronic • If acute will have respiratory acidosis Low oxygen level due to hypoventilation of (diseased) lungs • High CO2 due to increased levels in alveolar space and less removed from blood • Acute rise in blood CO2 leads to respiratory acidosis Hypoventilation due to any cause • Opiate toxicity • Neuromuscular disease • COPD • Acute severe asthma • Important to differentiate acute from chronic type 2 resp failure
Acute hypoventilation e.g. due to opiate toxicity leads to hypoxia,
hypercapnia and acidosis
• Chronic hypoventilation e.g. neuromuscular disease or severe COPD
leads to hypoxia and hypercapnia but may not have acidosis due to
compensation
Respiratory Alkalosis
Not usually associated with
respiratory failure
• Caused by hyperventilation
• Have low PCO2 and low H
Metabolic acidosis
usually a sign of a sick patient
• Excess acid production by the body e.g. lactic acidosis or
diabetic ketoacidosis
• Kussmal breathing is a classical clinical sign of acidosis as a
compensatory mechanism to increase CO2 removal from the
blood
• Full compensation is difficult: need to treat the underlying
cause of increased acid load e.g. treatment of DKA
Interpreting bicarbonate
Actual bicarbonate: • Calculated with actual H+ and pCO2 values • Standard bicarbonate: • Calculated with actual H+ and a pCO2 of 5.3kPa (normal pCO2 ) • Standard bicarbonate is therefore only influenced by metabolic effects
Base excess
The amount of base needed to be removed from a litre of blood
at a normal pCO2
in order to bring the H+ back to normal
• Sounds complicated but it’s not:
• It is calculated with a normal CO2
, so it only looks at the
metabolic component
• Normal value is zero (-2 to 2 mmol/l)
• A big negative value indicates a metabolic acidosis
• A positive value seen in compensated respiratory acidosis
high fever,
myalgia, sore throat and dry cough x24h
• On exam she has Temperature (T)= 39.1°C,
Pulse rate (PR)=88 beats per minute (bpm)
and respiratory rate (RR) 18/min.
flushed.
• Pharynx mild erythema.
• Chest occasional crackles on auscultation
Viral illnesses; Rhinoviruses (45-50%) ² Influenza A virus (25-30%) Usually transient • Complications sinusitis, pharyngitis, otitis media, bronchitis, rarely pneumonia • May lead to bacterial super-infection • Influenza A virus in particular causes systemic symptoms
A 74 year old man previously well apart from obesity and hypertension. • Developed fever, cough and loss of smell 10 days ago. • In last 2 days has become increasingly short of breath. • O2 saturations 86%, requiring 60% oxygen to maintain staturations at 93%
Emerging respiratory virus infections
SARS-CoV-2
(MERS-nCV)
A 19 year old presents with sore throat x 24 • He has noted tender glands in the neck • T 38.5°C, VS stable • Large tonsils with exudate • Tender anterior cervical LN
Pharyngitis Viral Streptococcus pyogenes, Glandular fever Epstein Barr virus Acute HIV infection
A 48 year old housewife presents with fever,
facial pain and purulent nasal discharge
• She has no fever but complains of pain in the left
ear and into the teeth
• She has seen her dentist who has found no dental
problems
• She has has cold 10 days ago and has had the
facial pain for a week
• She has a past history of allergic rhinitis and uses
a steroid nasal spray
Sinusitis Usually viral (as per causes URI) • Bacterial sinusitis (distinguish these from the viral cases to avoid inappropriate antimicrobial use) Streptococcus pneumoniae (40%), • Haemophilus influenzae (30-35%) • Other Moraxella catarrhalis Complications brain abscess, sinus vein thrombosis, orbital cellulitis
A 45 year old African woman presents with
sore throat and pain on swallowing
(‘odynophagia’)
• She is febrile, sitting in an erect position and
makes a high pitched wheezing noise when
she breathes in (‘inspiratory stridor’)
• She has been unwell for the last 6 months and
complains of fatigue, weight loss and
diarrhoea with oral thrush
Acute epiglottitis • Formerly an illness of children 2-4 year old who presented with fever, dysphagia, drooling and stridor • Caused by Haemophilus infuenzae type B (Hib) but now rare due to use of Hib vaccine • Adults can also have disease. ²Most severe due to Haemophilus influenzae ²also from causes of pharyngitis, other bacterial infections of airway ²Additional pathogens in immunocompromised e.g. AIDS
A 23 year old mother with a 4 month old child presents with a chronic cough • She has had a cough for four weeks and gets bouts of coughing during which she occasionally vomits • Denies fever or weight loss • On exam afebrile and vitals stable. Sub -conjunctival haemorrhage but lungs clear to auscultation
Bordatella pertussis
Adults chronic cough, paroxysms of coughing and 50% post
ptussive vomitting but fairly specific for pertussis
• Complications; pneumonia, encephalopathy,
subconjunctival haemorrhage
A 3 year old presents to casualty with his
mother
• He has a prominent barking cough and is
crying
• O/E febrile, RR40, cyanosed with prominent
intercostal recessions
• Has inspiratory stridor (a high pitched
wheezing noise due to turbulent airflow in
upper airway
Croup
• Acute laryngo-treacheobronchitis
• A disease of children , 6 yo , most 3mo-3
years)
• Mainly due to Parainfluenza viruses, ( also
RSV, IAV and other respiratory viruses)
A 3 month old child is admitted from casualty with severe respiratory distress • O/E O2 saturations 88% • RR 40, respiratory retractions • Widespread crackles and wheeze • The baby has a history of being born premature at 28 weeks gestation.
Bronchiolitis infections due to Respiratory syncytial virus (RSV) (80%) (rarely other viruses) • Inflammation of bronchioles and mucus production cause airway obstruction
Bronchitis
Aetiology:
Ø Frequently viral
Ø May be bacterial including Haemophilus influenzae or Streptococcus pneumoniae,
Moraxella catarrhalis, Mycoplasma pneumoniae
• Clinical Features:
Ø Cough may be productive or non-productive
Ø SOB and often wheeze
Ø May be fever but not systemic features of infection
Ø Wheeze but no signs of focal consolidation
• May cause acute exacerbations of COPD or asthma with increased wheeze
• Investigations:
Ø Arterial blood gas/oximetry for those with chronic lung disease-helps determine if need
hospitalisation
Ø CXR shows no features of pneumonia, usually normal
• Treatment:
Ø Usually none especially if viral, sometimes antimicrobials
Ø Manage exacerbation of COPD/asthma with steroids and increased inhalers
Bronchiectasis
Abnormal dilatation of airways and
suppurative infection
• Chronic scarring of lung with excessive sputum
production (‘bronchorrhoea’)
• Aetiology
üCongenital; Cystic fibrosis, ciliary dysfunction,
hypogammaglobulinemia
üPost-infectious; TB, suppurative pneumonia, measles ,
whooping cough
Other; Foreign body
Symptoms üChronic cough üCopius sputum üRecurrent pneumonia ü Weight loss • O/E üClubbing üCoarse ‘wet’ crackles • Can be complicated by haemoptysis
A 33 year old soldier presents with a 3 day history of dry cough and shortness of breath • O/E T 38.6°, PR 84, BP 114/76mm/Hg, RR=28 • O2 sat 95% • Dull Right mid lung, coarse crackles • WBC 7K
Pneumonia
• Streptococcus pneumoniae (40%)
• Mycoplasma pneumoniae (~10% peaks in epidemic
seasons)
• Chlamydophila pneumoniae (~10%)
• Legionella pneumophila and other spp.(<5%)
• Haemophilus influenzae (<5%)
• Klebsiella pneumoniae (rare; homeless and in hospital)
• Staphylococcus aureus (low % in community but
increased after influenza and in hospital especially)
• Viruses (≥10%)
Community Acquired Pneumonia
CAP
Incidence 5-11 per 1,000 • 20-50% Hospitalised, 5-10% require ITU • Mortality 1% community, 10% in hospital, 30% ITU • Hospitalisation 6-8 days • Costs > £400 millions/ year to the UK • Significant short and long term mortality from other causes after pneumonia
S. pneumoniae
any age but increases at extremes of age
ücan be severely ill with respiratory failure or sepsis
Mycoplasma pneumoniae
usually younger adult, milder illness
ümay have extrapulmonary features; haemolytic anaemia
(cold agglutinins),Raynauds (cold agglutinins) erythema
multiforme, bullous myringitis (blisters on tympanic
membrane), encephalitis
Chlamydophila pneumoniae
like M. pneumoniae, maybe older age group more
prolonged wheezing
Pneumonia
Extra-pulmonary features;
Ødiarrhoea,
Øabnormal liver function tests,
Øhyponatremia,
Ømyalgia, raised creatinine kinase,
Øinterstitial nephritis,
Øencephailitis, confusion
eatment
• Prompt but appropriate initiation of antimicrobials;
ideally establish diagnosis and start treatment ≤4h
• Use narrowest spectrum to stop spread of resistance,
MRSA acquisition and Clostridium difficile inf
A 52 year old man is admitted with a three
month history of cough, weight loss and night
sweats
• T 37.8°C, PR 80, BP 112/60, RR18
• Cachectic
• Coarse crackles and reduced air entry right
upper lobe
Tuberculosis
• Chronic respiratory tract infection (can also be extrapulmonary), usually due to reactivation of
latent infection.
• Specific epidemiological groups e.g.
ü exposed to a case
ü born in country of high incidence,
ü homeless,
ü alcoholic HIV infection, anti-TNF treatment
• Clinical features;
ü Cough, hemoptysis, short of breath
ü weight loss, fever, night sweats,
ü swollen lymph nodes or other extrapulmonary features
• Multiple radiological appearances but
ü upper lobe disease with cavities,
ü pleural disease,
ü multiple tiny nodules (‘miliary’),
ü lymphadenopathy in chest
• and failure to resolve with routine antibiotics all suggestive
Patients require isolation if admitted as may be highly infectious to others
Obstructive Lung Diseases
Asthma • Chronic Obstructive Pulmonary Disease (COPD) • Causing obstructive picture • Bronchiectasis • Cystic Fibrosis
Factors Affecting Airway Internal Diameter
Increased mucus production
• Anatomical features
• Autonomic and Non-Adrenergic/Non-Cholinergic (NANC) systems
• Inflammation
How do we measure obstruction
Peak flow
• Spirometry
• Lung Volumes and flow
Peak Flow
Peak expiratory flow rate (PEFR) • Measures maximum speed of expiration • Crude measurement of conducting airway flow • Can aid in Asthma diagnosis/management • Excellent bedside and patient based tool
FEV1
How much can the patient exhale in a given time, e.g. 1
second:
FVC
How much they can exhale altogether:
Ratio of FEV1
to FVC
Useful to differentiate between obstruction and restriction
• If less that 0.7 then suggests obstructive airways pathology
• In mild obstruction biggest impact on FEV1
• In severe obstruction also lose FVC
Reversibility of spirometry
Used as a diagnostic test in Asthma e.g. following bronchodilator
• Asthma reversible vs. COPD fixed airways obstruction
• Can also use bronchial challenge agents (histamine) to induce
bronchospasm and obstructive spirometry
Localised Airway Obstruction
Airway obstruction
• Lesion outside the wall e.g. large lymph node
• Lesion in the wall e.g. tumour
• Lesion in the lumen e.g. foreign body
• Causes distal collapse or over-inflation
• May be distal lipid or infective pneumonia
• Normal pulmonary function tests
Diffuse Obstructive Airways Disease
Reversible and intermittent OR Irreversible and persistent • Centred on bronchi and bronchioles • Diffuse disease as many airways involved • Pulmonary function tests ‘obstructive’ • Reduced vital capacity (VC) • Reduced FEV1 / FVC ratio • Reduced peak expiratory flow rate Several clinico-pathological entities • Chronic bronchitis • Emphysema • Asthma • (Bronchiectasis) • Chronic obstructive pulmonary disease (COPD) • Spectrum of co-existence of chronic bronchitis and emphysema
Host Defences
Defences • Cough reflex • Cilia • Mucus • Antibody deficiency e.g. IgA • Immunosuppression - disease, drugs • Macrophage dysfunction • Pulmonary oedema
Chronic Bronchitis
Clinical definition • Cough and sputum for 3 months in 2 consecutive years • Aetiology - pollution, smoking • Clinical • Middle-aged heavy smokers • Recurrent low-grade bronchial infections (exacerbations) • H. influenzae, S. pneumoniae, viruses • Airway obstruction may be partially reversible Progression of disease • Hypercapnia • Hypoxia • Pulmonary hypertension • ‘Cor pulmonale’ - right ventricular failure • ‘Blue bloater’
Emphysema
• Irreversible dilatation of acinar spaces with
destruction of walls
• Traditional definition confined to alveoli but often
extended to include respiratory bronchioles
• Associated with loss of surface area for gas
exchange
Strongly associated with smoking
• Seen in some with pneumoconiosis, particularly
coal-workers
• Most commonly in upper lobes
• Respiratory bronchiolitis often present
Paraseptal
• Distension adjacent to pleural surfaces
• May be associated with scarring
• Irregular
• Associated with scarring
• Overlap with paraseptal emphysema
• Others
• Bullous: distended areas >10mm
• Interstitial
Clinical features
• Hyperventilation
• Normal pO2, pCO2
• ‘Pink puffer’
• Weight loss
• Right ventricular failure
• Often co-existing chronic bronchitis, in which case
clinical features are mixed
Chronic Obstructive Pulmonary Disease
• A combination of the features of chronic bronchitis
and emphysema
• Most patients exhibit a mixture of features
• Typically assessed using pulmonary function tests
e.g. FEV1/FVC < 0.7 for diagnosis and percent
predicted FEV1 to assess severity
FEV1 – forced expiratory volume in 1 second
FVC – forced vital capacity
Asthma
Reversible wheezy dyspnoea’ • Increased irritability of the bronchial tree with paroxysmal airway narrowing • Five aetiological categories • Atopic • Non-atopic • Aspirin-induced • Occupational • Allergic bronchopulmonary aspergillosis (ABPA)
Asthma can lead to
sudden death due to
mucus plugging
Atopic Asthma
Associated with allergy
• Triggered by a variety of factors
• Dust, pollen, house dust mite etc etc
• Often associated with eczema and hay fever
• Bronchoconstriction mediated by a type I
hypersensitivity reaction
Hypersensitivity reaction leads to:
• Bronchial obstruction with distal overinflation or
collapse
• Mucus plugging of bronchi
• Bronchial inflammation
• Mucous gland hypertrophy
• Bronchial wall smooth muscle hypertrophy
• Thickening of bronchial basement membranes
Non-Atopic Asthma
- Associated with recurrent infections
- Not immunologically mediated
- Skin testing negative
Aspirin-induced Asthma
• Associated with recurrent rhinitis, nasal polyps
and urticaria
Occupational Asthma
Hypersensitivity to an inhaled antigen
• May be non-specific in those with hyper-reactive
airways
• May be a specific allergic response
Hypersensitivity to an inhaled antigen
• May be non-specific in those with hyper-reactive
airways
• May be a specific allergic response
Specific allergic response to the spores of Aspergillus
fumigatus
• Mixed type I and type III hypersensitivity reaction
• Mucus plugs common
• Associated with bronchiectasis
• Not to be confused with an aspergilloma, which is a
fungal ball, usually colonising a pre-existing cavity in
the lung (often tuberculous)
Bronchiectasis
• Permanent dilatation of bronchi and bronchioles
• Due to a combination of obstruction and inflammation
(usually infection)
• May be localised or diffuse, depending on cause
• Historically seen in patients with pulmonary
tuberculosis involving hilar lymph nodes
• Classically associated with childhood infections,
particularly measles and whooping cough
• Diffuse bronchiectasis seen in patients with cystic
fibrosis
Clinical features
• Chronic cough productive of copious
sputum
• Finger clubbing
• Complications
• Spread of infection
• Pneumonia, Empyema, Septicaemia, Meningitis,
Metastatic abscesses e.g. brain
• Amyloidosis
• Respiratory failure
Defence mechanisms
Immunological
• IgA & antimicrobials in mucus
• Resident alveolar macrophages & dendritic cells
• Innate / adaptive immune responses
73 year old woman. Smoker. History of colorectal cancer (right hemicolectomy
2018) and currently undergoing post-op chemotherapy and radiotherapy.
Presents with three day history of shortness of breath, cough and haemoptysis,
pyrexia
Examination: Right basal crepitations
Bloods: WBC 16.2 (neutrophils 14)
Chest x-ray: Right basal consolidation
Diagnosis: Pneumonia Cough • Sputum • Pyrexia • Pleuritic chest pain • Haemoptysis • Dyspnoea • Hypoxia
Acute respiratory distress syndrome
ncidence 10-14/100,000/yr • Mortality rate ~40% • Clinical diagnosis • Hypoxia (PaO2/FiO2 ≤ 300mmHg ) • Non-cardiogenic pulmonary oedema • Causes • Direct – pneumonia, aspiration, hyperoxia, ventilation • Indirect – sepsis, trauma, pancreatitis, acute hepatic failure
Tuberculosis
• Predisposing factors • Alcoholism • Diabetes mellitus • HIV / AIDS • Some ethnic groups Treatment • Socio-economic conditions • Drugs – triple antibiotic therapy • Prevention e.g. BCG vaccination
Tuberculous bronchopneumonia
Infection spreads via bronchi
• Results in diffuse bronchopneumonia
• Well developed granulomas do not form
• Miliary Tuberculosis
- Infection spreads via blood-stream
- Organisms scanty
- Multiple organs
- lungs, liver, spleen, kidneys, meninges, brain
Complications of Bronchiectasis
Local • Distal airway damage / loss and lung fibrosis • Pneumonia • Pulmonary abscess formation • Haemoptysis • Physiological complications • Respiratory failure • Cor pulmonale • Systemic complications • Metastatic abscess • Amyloid deposition
15 year old boy. Long history of productive cough and thick purulent
sputum.
Diagnosis of bronchiectasis on CT scan.
• 69 year old retired coal miner. Presents with slowly worsening
shortness of breath, cough and ankle oedema
• CT scan – honeycomb and ground glass changes in both lower lobes
• Restrictive defect on pulmonary function tests
Idiopathic pulmonary fibrosis
Acute inflammation
- Pneumonia
* Neutrophils & macrophages
Granulomatous inflammation
Tuberculosis
• Host pathogen interactions
Fibrosing lung diseases
Defective repair mechanisms
• Failure of clearance
OBSTRUCTIVE DISORDER
A disorder in which the radius of an airw
RESTRICTIVE DISORDER
A disorder in which prevents normal expansion of the lungs
Lung restriction can occur due to:
Extra-pulmonary disease i.e. visceral pleura, pleural space, chest wall including parietal pleura, bones, muscles, nerves scoliosis asbestos exposure myasthenia gravis
Intra-pulmonary disease i.e. alveoli and surrounding lung tissue (=parenchyma) Rheumatoid-lung Asbestosis Silicosis in a pneumoconiosis stonemason
COMPLIANCE
This is the measure of distensibility (stretchability) of a tissue
A lung with low compliance means a greater inflation pressure is
required to inflate the lung.
A lung with low compliance generates more elastic recoil i.e. it
deflation is easy
A lung with high compliance means a smaller inflation pressure is
required to inflate the lung
A lung with high compliance generate less elastic recoil i.e.
deflation is hard
Surfactant
produced by alveolar Type II cells
• composed of lipids (90%, mainly phospholipids) and proteins (10%)
• reduces surface tension
Respiratory Distress Syndrome of the
Newborn
CAUSE = lack of SURFACTANT
Surfactant in adults
Adult respiratory distress syndrome (ARDS) • Pneumonia • Idiopathic pulmonary fibrosis • Lung transplant ……
RISK
HAZARD X EXPOSURE
bronchodilators relax smooth muscle dilating airways
most common:
beta 2 agonists (salbutamol), anticholinergics (ipatropium), methylxanthines (theophyline)
corticosteroids
anti-inflammatory drugs normally administered by inhalation (beclometasone) sometimes given by mouth (predinsolone) during disease exacerbations
leukotreine receptor antagonists
motelukast inhibit the activity of leukotrienes and have both anti-inflammatory and bronchodilator effects
adverse respiratoey function
bronchoconstriction, inflammation, fibrosis, suppress of respiration
common bronchoconstrictors
beta blockers, NSAIDs (aspirin, ibuprofen)
paradoxical bronchospasm caused by inhaled beta 2 agonists occasionally
commonest drugs associtaed with interstitial lung disease
antibiotics (nitrofuratonin, anti-rheumatic drugs (bleomycin), anti arrhythmic (amiodarone)
respiratory depression
opiod analgesics (morphine, oscydocone) benzodiazepines (diazepam), barbiturates (ethanol and oxygen)
beta 2 agonists
activate beta 2 adrenocreptors in bronchial smooth muscle leading to generation of secondary messenger cAMP by adenylate cyclase the commonly used drugs ate short acting salbutamol and long acting salmeterol
adverese effects of beta 2 activation
tremor, palpitations, arrhythmias, hyperglycaemia
antimuscarinics
antagonise muscarinic M3 receptors and reduce generation of ionsitol triphosphate and availability of calcium ions, commonly given by inhalation and either short acting (ipratropium bromide) or long acting (tiotropium)
antimuscarinics
cause drymouth, blurred vision, tachycardia, constipation, urinary retention, glaucoma
methylxanthines
theophlline are phosphodiesterase inhibiotrs that reduce breakdown of cAMP and potentiate the activity of beta 2 adrenorecptors they are given by mouth or intravenously n emergenciees
theophlines
narrow therapeutic range and significant inter individual variation in pharmaco kinetics drug interactions
