Resp Flashcards
normal values of FEV1, FVC and FEV1/FVC?
FEV1 - <80% abnormal
FVC <80 abnormal
FEV1/FVC <0.7 = airway obstruction and normal FEV1/FVC but low FVC = airway restriction
type 1 and type 2 respiratory failure?
type 1; hypoxia and normal or low co2 -> typically caused by PE
type 2; hypoxia and hypercapnia
signs of hypercapnoea?
- Bounding pulse
- Flapping tremor
- Confusion
- Drowsiness
- Reduced consciousness
obstructive lung disease?
- FEV1/FVC below 0.7
- FEV1 lower than FVC
- ASTHMA and COPD
restrictive lung disease?
• FEV1/FVC above 0.7 • FVC & FEV1 below 80% predicted value • Due to restriction, lung volumes are small and most of breath is out in first second • Interstitial lung disease: - FIBROSING ALVEOLITIS - SARCOID
transfer co-efficent?
• Measure of ability of oxygen to diffuse across the alveolar membrane
• Can calculate by inspiring a small amount of carbon monoxide (not too
much since can kill) then hold breath for 10 seconds at total lung
capacity (TLC) then the gas transferred is measured
low in; COPD and anaemia
high in; pulmonary haemorrhage
COPD
• A disease state characterised by airflow limitation that is not fully reversible
• The airflow limitation is usually both progressive and associated with an abnormal
inflammatory response of the lungs to noxious particles or gases
epidemiology of COPD?
- middle age
aetiology of COPD?
- CIGARETTE SMOKING is the MAJOR cause of COPD and is related to the
daily average of cigarettes smoked and years spent smoking - Chronic exposure to:
• Pollutants at work (mining, building and chemical industries)
• Outdoor air pollution
• Inhalation of smoke from biomass fuels used in heating and cooking in
poorly ventilated areas
• These factors also play a role, particularly in developing countries - Alpha-1 antitrypsin deficiency:
• Causes early onset COPD (due to proteolytic lung damage)
• A rare cause of cirrhosis (due to accumulation of the abnormal protein
in the liver)
• Mutations in the alpha-1 antitrypsin gene on chromosome 14 lead to
reduced hepatic production of alpha-1 antitrypsin which normally
inhibits the proteolytic enzyme - neutrophil elastase
pathophysiology of COPD?
- There is increased numbers of mucus-secreting goblet cells in COPD within
the bronchial mucosa, especially in the larger bronchi - In more advanced cases the bronchi become overtly inflamed and pus is seen
in the lumen - causes chronic bronchitis and emphysema
- The combination of emphysema (loss of elastic recoil of the lung with collapse
of small airways during expiration) and chronic bronchitis (airway narrowing)
results in severe airflow limitation - V/Q (ventilation perfusion) mismatch is partly due to damage and mucus
plugging of smaller airways from the chronic inflammation and partly due to
rapid closure of smaller airways in expiration owing to the loss of elastic
support - this mismatch leads to a fall in PaO2 and increased work or
respiration
chronic bronchitis - COPD physiology
• There is airway narrowing and hence airflow
limitation as a result of hypertrophy and
hyperplasia of mucus secreting glands of
the bronchial tree, bronchial wall
inflammation and mucosal oedema
• Microscopically there is infiltration of the
walls of the bronchi and bronchioles with
acute and chronic inflammatory cells
• The epithelial layer may become ulcerated and, with time, squamous
epithelium replaces the columnar cells (squamous metaplasia) when
the ulcer heals
• The inflammation is followed by scarring and thickening of the walls,
which narrows the small airways
• The small airways are particularly affected early in the disease, initially
without the development of any significant breathlessness
• The initial inflammation is reversible and accounts for the improvement
in airway function if smoking is stopped early
• In the later stages, the inflammation continues, even if smoking is
stopped
• Patients chronic bronchitis are referred to as blue bloaters
emphysema - COPD pathology
• Defined as dilatation and destruction of the lung tissue distal to the
terminal bronchioles
• Results in loss of elastic recoil, which normally keeps the airways open
during expiration
• Leads to expiratory airflow limitation and air trapping
• Premature closure of airways limits expiratory flow while the loss of
alveoli decreases capacity for gas transfer
• Patients with emphysema are referred to as the pink puffers
types of emphysema
- Centri-acinar emphysema:
• Distension and damage of lung tissue is concentrated around
the respiratory bronchioles, whilst the more distal alveolar
ducts and alveoli tend to be well preserved
• Extremely common - Pan-acinar emphysema:
• Less common
• Distension and destruction affect the whole acinus and in
severe cases the lung is just a collection of bullae
• Associated with alpha-1 antitrypsin deficiency - Irregular emphysema:
• Scarring and damage that affects the lung parenchyma
patchily, independent of acinar structure
pathogenesis of cigarette smoking?
- Causes mucus gland hypertrophy in the larger airways and leads
to an increase in neutrophils, macrophages and lymphocytes in
the airways and walls of the bronchi and bronchioles - These cells release inflammatory mediators (elastases, proteases,
IL-1,-8 & TNF-alpha) that attracts inflammatory cells (further
amplify the process), induce structural changes and break down
connective tissue (protease-antiprotease imbalance) in the lung
resulting in emphysema - Inactivates the major protease inhibitor alpha-1 antitrypsin
clinical presentation of COPD?
- Characteristic symptoms are productive cough with white or clear sputum,
wheeze and breathlessness, usually following many years of a smokers
cough - Systemic effects include:
• Hypertension
• Osteoporosis
• Depression
• Weight loss
• Reduced muscle mass with general weakness - pulmonary hypertension due to hypoxic kidney
investigations of COPD?
- Based on a history of breathlessness and sputum production in a chronic
smoker - In the absence of a history of cigarette smoking then asthma is a more likely
explanation, unless there is a family history suggesting alpha-1 antitrypsin
deficiency - LUNG FUNCTION TEST -> fev1/fvc <0.7
- CXR -> maybe normal or shower hyper inflated lungs
- ABG
COPD treatment?
- SMOKING CESSATION IS MOST USEFUL,
- BRONCHODILATOR - LABA eg, salmterol or SABA eg, salutomal
- LAMA - eg, tiotropium bromide
- corticosteroid eg, prednisolone
asthma? epidemiology
- Commonly starts in childhood between the ages 3-5 years and may either
worsen or improve during adolescence - Peak prevalence between 5-15 years
3 key characteristics of asthma?
- Airflow limitation - usually reversible spontaneously or with treatment
- Airway hyper responsiveness (ADAM33)
• Bronchial inflammation with T lymphocytes, mast cells, eosinophils
with associated plasma exudation, oedema, smooth muscle hypertrophy,
mucus plugging and epithelial damage
types of asthma?
• Allergic/eosinophilic asthma (70%):
- Allergens (e.g. fungal allergens and pets etc.) & atopy (readily develop IgE)
• Non-allergic/non-eosinophilic (30%):
- Exercise, cold air & stress
- Smoking & non smoking associated
- Obesity associated
PATHOPHYSIOLOGY OF ASTHMA?
- Primary abnormality in asthma is narrowing of the airway which is due to
smooth muscle contraction, thickening of the airway wall by cellular
infiltration and inflammation and the presence of secretions within the airway
lumen - Inflammation: MAST CELLS bind to IgE and will respond if allergen binds to IgE; it releases histamine (bronchconstriction), tryptase, prostaglandin 2, cytokines
- Eosinophils release proteins and peroxidase which are toxic to epithelial cells
first bronchoconstriction then inflammation due to immune cell infiltration and then worsening inflammation due to eosinophil
remodelling - hypertrophy and hyperplasia causing excess airway narrowing
clinical presentation of asthma
- Intermittent dysponea (difficulty breathing)
- Wheeze
- Cough (especially nocturnal) - frequent symptom in children
- Sputum
- Symptoms worse at night
life threatening asthma attack?
- Silent chest
- Confusion & exhaustion
- Cyanosis (PaO2 less than 8kPa)
- Bradycardia
- PEFR less than 33%
immediate management for asthma attack
• Oxygen therapy to maintain O2 sat (94%-98%)
• Nebulised 5mg salbutamol (+ ipratropium if life threatening) - repeat/IV
infusion
• Prednisolone (with or without hydrocortisone IV)
• Take arterial blood gases and repeat within 2 hours if severe attack or
patient deteriorating
• Chest X-ray if fails to respond to treatment
• Check PEFR within 15-30 mins/regularly
• Oximetry to ensure SaO2 is greater than 92%
investigations for asthma?
- take history - ADL
- lung function test; PEFR; if >15% improvement with bronchodilator = asthma
- exercise test
- blood and sputum test -> eosinophil
treatment of asthma?
- bonrchodilator -> SABA eg, salbutamol and LABA eg, salmeterol
- muscarinic antagonist -> short acting IPRATROPIUM and long acting TIOTROPIUM (M3 receptors)
- corticosteroids eg, prednisolone
- monoclonal antibody OMALIZUMAB
hypersensitivity pneumonitis?
• Previously called extrinsic allergic alveolitis
• Type of Interstitial Lung Disease (ILD) - distinct cellular infiltrates and
extracellular matrix deposition in lung distal to the terminal bronchiole i.e.
diseases of the alveolar/capillary interface
epidemiology of hypersensitivity pneumonitis?
- adults
- associated with specific occupations eg, farmers
- bird keeping
FARMERS LUNG MOST COMMON
pathophysiology of hypersensitivity pneumonitis?
- The allergic response to the inhaled antigen involves both cellular immunity
and the deposition of immune complexes (TYPE 3 HYPERSENSITIVITY REACTION) resulting in inflammation through the activation of complement
via the classical pathway - These mechanisms attract and activate alveolar and interstitial macrophages
so that continued antigenic exposure results in the progressive development
of pulmonary fibrosis - In the acute phase; the alveoli are infiltrated with acute inflammatory cells
- With chronic exposure, granuloma formation and obliterative bronchiolitis
(inflammation of bronchioles) occur
farmers lung?
• Fungus in mouldy hay is inhaled
• If individual is already sensitised to the organism, a type III immune
complex hypersensitivity reaction follows
• Clinically there is acute dyspnoea (difficulty breathing) and cough a few
hours after inhalation of the antigen
• One of the earliest features is bronchiolitis
• Later, chronic inflammatory cells are seen in the interstitium together
with non-caveating granulomas
• The inflammatory process may resolve on WITHDRAWAL of the antigen
but if there is chronic exposure then pulmonary fibrosis (build up of scar
tissue, makes lungs stiff) will develop
clinical presentation of hypersensitive pneumonitis
- Acute (4-6hrs post-exposure): • Fever • Rigors • Myalgia • Dry cough • Dyspnoea • Crackles (no wheeze)
- Subacute:
• Occurs with intermittent or lower-level exposure
• History or repeated acute attacks
• Signs same as acute, symptoms less severe and more gradual onset - Chronic:
• Usually no history of preceding acute symptoms
• If the source of antigen is removed only partial improvement of
symptoms
• Cyanosis and clubbing may develop
• Weight loss
• Increasing dyspnoea
• Type 1 respiratory failure (low paO2, normal/low paCO2)
investigation of hypersensitivity pneumonitis
- Chest X-ray:
• Fibrotic shadow in upper zone of lung (upper zone mottling/
consolidation)
• Diffuse small nodules and increased reticular shadowing may be
present but not specific - FBC; ESR and WCC raised
- Lung function test
treatment for hypersensitive pneumonitis?
- Acute:
• Remove allergen
• Give O2 (35-60%)
• Oral prednisolone (corticosteroid) followed by reducing dose
- Chronic: • Avoid exposure to allergen • Long term steroids can often achieve chest x-ray and physiological improvement • Corticosteroids e.g. prednisolone
occupational lung disorders?
- Response to inhaling something at work
* Can be; fumes, dust, gas or vapour
coal workers pneumoconiosis
- Pneumoconiosis means the accumulation of dust in the lungs and the
reaction of the tissue to its presence - Common dust disease in countries that have or have had coal-mines
- Caused by the inhalation of coal dust particles over 15-20yrs
- These particles are ingested by alveolar macrophages in the small
airways and alveoli which then die, releasing enzymes and causing
fibrosis and simple pneumoconiosis where there is fine micro nodular shadow in CXR -> progress onto progressive massive fibrosis
progressive massive fibrosis -> fibrotic mass is in the upper lobes and RF and ANA are [resent in serum
- destruction in lung causing emphysema and airway damage
silicosis?
- Uncommon but seen in stonemasons, sand-blasters, pottery and
ceramic workers and foundry workers involved in fettling - Caused by the inhalation of silica particles (silica dioxide) which is very
fibrogenic - Silica is particularly toxic to alveolar macrophages and readily initiates
fibrogenesis - CXR appearance show diffuse nodular pattern in upper and mid-zone
and thin streaks of calcification (egg-shell calcification) of the hilar
nodes - Spirometry shows a restrictive ventilatory defect
- Patients have progressive dyspnoea and an increased incidence of TB
asbestos?
- Has widely been used in roofing, insulation and fireproofing due to its
resistance to heat, acid and alkali - they are fibrogenic
- Significant time lag between exposure and development of disease,
particularly mesothelioma (20-40 years) - Risk of primary lung cancers (usually adenocarcinomas) is increased
in people exposed to asbestos, even in non-smokers
bronchiectasis
• Chronic infection of the bronchi and bronchioles leading to permanent
dilatation of these airways
• Clinically the disease is characterised by productive cough with large
amounts of discoloured sputum and dilated, thickened bronchi detected on
CT
epidemiology of bronchiectasis?
W>M
- increasing age
- result of chronic infection -> damages lung -> scarring -> dilation
causes of bronchiectasis?
• Post infection (most common):
- Previous pneumonia
- Granulomatous disease e.g. Mycobacterium tuberculosis (TB)
- Measles, Whooping cough
• Congenital:
- Cystic fibrosis
• Mechanical bronchial wall obstruction:
- Foreign body
• Allergic bronchopulmonary aspergillosis (ABPA) - immunological over-
response
• HIV
pathophysiology of bronchiectasis?
- Failure of mucociliary clearance and impaired immune function contribute to
continued insult to bronchial wall, through the recruitment of inflammatory
cells and uncontrolled neutrophilic inflammation; bronchitis →
bronchiectasis → fibrosis - Airways dilate due to pulmonary inflammation and scarring, as fibrosis
(surrounding scar tissue) contracts - Secondary inflammation changes lead to further destruction of airways
clinical presentation of bronchiectasis?
- Usually the lower lobes are affected
- Chronic cough with production of copious amounts of foul smelling purulent
sputum (khaki coloured) - sometimes flecked with blood (intermittent
haemoptysis) - Dyspnoea
investigation of bronchiectasis?
- CXR:
• Dilated bronchi with thickened walls (tramline and ring shadows)
• Multiple cysts containing fluid showing up as cystic shadows - Sputum culture:
• To see bacterial colonisation status - High resolution CT (HRCT):
• Thickened, dilated bronchi with cysts at the end of bronchioles
• Airways larger than associated blood vessels
bronchiectasis management?
- Improved mucus clearance:
• Postural drainage: Where physio tips patients so the affected lobes can
drain mucus- done 3 times a day for 10-20mins
• Chest physio - Abs
- bronchodilators eg, nebulised salbutamol
cystic fibrosis?
• One of the most commonest lethal autosome RECESSIVE conditions in
CAUCASIANS, 25% condition and 50% carrier risk
cystic fibrosis, epidemiology
- more common in Caucasians
- family history
- pancreatic insufficiency
pathophysiology of cystic fibrosis
- CF gene located on long arm of ch7 as CFTR - cystic fibrosis transmembrane regulator protein
- CFTR - cl- channel and it actively imports negative ions causing an osmotic gradient of water moving out of cell into mucus
- mutation of this protein - F580 deletion causing defective cl- secretion and increased h20 absorption into cells -> thickened secretions
clinical presentation of cystic fibrosis
- Neonates: • Failure to thrive • Meconium ileus - bowel obstruction due to thick meconium (earliest stool) • Rectal prolapse
- Respiratory (upper & lower): • Cough • Thick mucus • Wheeze • Recurrent infections • Bronchiectasis & airflow limitation • Sinusitis
- Alimentary:
• Thick secretions
• Reduced pancreatic enzymes (due to mucus blocking pancreatic duct)
• Pancreatic insufficiency (diabetes mellitus & steatorrhoea (fatty stools
since enzymes not released to digest fat)
other
- clubbing
- osteoporosis
investigations for cystic fibrosis
- Clinical history
- Family history of disease
- One or more of these:
• Sweat test: will show high sodium & chloride concentrations greater
than 60mmol/L (Cl- will be higher)
• Absent vas deferens and epididymis (male urogenital abnormality)
• GI & nutritional disorders - Genetic screening for known CF mutations
treatment for cystic fibrosis
- stop smoking
- Prophylaxis antibiotics:
• Flucloxacillin - Staphylococcus Aureus
• Amoxycillin - Haemophilus influenzae - Regular chest physiotherapy (postural drainage, forced expiratory
techniques) - B2 agonists (salbutamol) & inhaled corticosteroids (beclometasone) -
purely for symptomatic relief - Mucolytics such as Dornase alfa (nebulised) or inhaled DNAse - to clear
airways of mucus - Amiloride - inhibits Na+ transport thus less thick mucus
sarcoidosis
• Type of Interstitial Lung Disease - distinct cellular infiltrates and extracellular
matrix deposition in lung distal to the terminal bronchiole i.e. diseases of the
alveolar/capillary interface
• Typically presents with bilateral hilar lymphadenopathy, pulmonary
infiltration and skin or eye lesions
sarcoidosis epidemiology
- 20-40 yrs
- W>M
- first degree relatives
sarcoidosis pathophysiology
- Typical sarcoid granulomas consist of focal accumulations of epithelioid
cells, macrophages and lymphocytes - mainly T cells - Generally unknown
sarcoidosis clinical presentation?
- Acute sarcoidosis commonly presents with erythema nodusum (red lumps
form on the shins and less commonly thighs and forearms) with/without
polyarthralgia (aches in joints and joint pain) - it usually resolves
spontaneously - Constitutional symptoms:
• Fever
• Weight loss
• Fatigue
- Respiratory symptoms: • 90% have abnormal CXRs with bilateral hilar lymphadenopathy with/ without pulmonary infiltrates/fibrosis • Dry cough • Progressive dyspnoea • Reduced exercise tolerance • Chest pain
investigations of sarcoidosis
- CXR; bilateral hilar lymphadenopathy and pulmonary infiltrates
- FBC; raised ESR
- tissue biopsy; DIAGNOSTIC
treatment for sarcoidosis
- Acute sarcoidosis:
• Bed rest
• NSAIDs - Corticosteroids:
• Prednisolone orally then gradually reduce dose
• In severe illness give IV methylprednisolone
• If steroid-resistant then: - Methotrexate but close monitoring required
idiopathic pulmonary fibrosis
type of interstitial lung disease where there is patchy fibrosis or the interstitium and minimal or absent
inflammation, acute fibroblastic proliferation and collagen deposition
epidemiology of idiopathic pulmonary fibrosis
- A progressive chronic pulmonary fibrosis of unknown aetiology although
20% of patient give a history of occupational exposure to metals and wood
dusts - Mean onset is in the sixties and presentation is very uncommon under the age
of 50 - Males are twice as likely to be affected
pathophysiology of idiopathic pulmonary fibrosis
- The pathogenesis of IPF is unknown
- It is thought that repetitive injury to the alveolar epithelium, caused by
currently unidentified environmental stimuli leads to the activation of
several pathways responsible for repair of the damaged tissue - However in IPF, the wound healing mechanisms become uncontrolled,
leading to the over-production of fibroblasts and deposition of increased
extracellular matrix in the interstitium (fibrosis) with little inflammation - The structural integrity of the lung parenchyma (functional tissue of organ) is
therefore disrupted; there is loss of elasticity and the ability to perform gas
exchange is impaired, leading to progressive respiratory failure
risk factors of idiopathic pulmonary fibrosis?
- cigarette smoking
- infectious agents CMV, HEP C and EBV
- occupational dust
- drugs eg, methotextrate
- GORD
- genetics
clinical presentation of idiopathic pulmonary fibrosis
- Dry cough with/without sputum
- Exertional dyspnoea
- Malaise
- Weight loss
- Arthralgia (joint pain)
- Cyanosis
- Finger clubbing
investigations of idiopathic pulmonary fibrosis?
- ABG; low pa02
- raised CRP and immunoglobulins
CXR; small volume lungs with increased reticular shadowing
HRCT - confirm diagnosis
lung biopsy
treatment of idiopathic pulmonary fibrosis
- oxygen
- pulmonary rehabilitation
- treat GORD and cough
- Pirfenidone - an antifibrotic agent that can slow the rate of FVC decline
(need to check eligibility)
