Week 8 Resp Flashcards
Alveolar and arterial O2 gradient
Difference between PAO2 and PO2:
2-4: normal
More indicates V/Q mismatch
Less indicates hypoventilation
Spirometry
Forced expiration from total lung capacity, followed by a full inspiration
Measures lung function
Disadvantages:
Requires trained technician
Patient is too frail, unwell
Obstructive lung disease
FEV1/FVC ratio <70% (FEV1 decreased more than FVC)
Asthma, COPD
Severity of COPD depends on %FEV1
mild = 80%
mod = 50 - 79%
severe = 30 - 49%
very severe = < 30%
If reversible by 15% and 400mL FEV1 with salbutamol then indicates asthma
Residual volume and TLC (total lung capacity) increased - air trapping
Transfer factor reduced due to emphysema
Asthma investigations
Spirometry
PEFR
Bronchial provocation - give metocholine or histamine. If there is a decrease in 20% FEV1, indicates asthma
Restrictive lung disease
Both FEV1 and FVC reduced so ratio >70%
Flow-volume loop looks same shape but smaller
Causes:
Interstitial lung disease
Kyphoscoliosos
Obesity
Gullain-Barre syndrome
Lung volumes reduced
Transfer factor
Give small amount of carbon monoxide and measure expired gas
Measures how well lungs are exchanging gas
Affected by:
alveolar surface
Hb conc
V/Q mismatch
Reduced in:
Interstitial lung disease
Emphysema
Anaemia
2 ways to measure residual volume
Residual volume - gas left after expiration
Helium dilution - spirometer contains helium, pt breathes it in and out, spirometer measures helium conc
Body plethysmography
Oximetry
Non-invasive measurement of saturation of Hb by O2
Does not measure CO2 so no measurement of ventilation
Main causes of hypoxaemia
V/Q mismatch (pneumonia, COPD)
Shunt (congenital heart disease)
hypoventialtion (drugs)
low inspired O2 (high altitude)
COPD (def, symptoms, pathophys, signs on CXR)
Progressive, non-reversible airway obstruction that does not change markedly over months
Assoc. with smoking
Genetics: Alpha-1-trypsin deficiency (serine proteinase inhibitor)
Symptoms:
Over 35, ex/smoker with:
Chronic cough, sputum production, wheeze, winter bronchitis, exertional breathlessness
Complications:
Hypoxaemia
Can lead to cor pulmonale (hypertrophy of R ventricle due to increase pulmonary hypertension)
Clinical spectrum:
Chronic bronchitis (sputum production on most days for 3 months in 2 years)
- Leads to hyperplasia of mucus glands in larger airways, and hypersecretion of mucus
- Chronic inflammatory infiltrate - CD8 T cells, macrophages, neutrophiles
- Inflammation leads to scarring and thickening of airways
Small airway disease: early process in COPD
- goblet cell hyperplasia, mucus plugging, inflammation
Emphysema (abnormal enlargment of airspaces distal to terminal bronchioles)
Centri-acinar (damage around resp bronchioles, mostly upper lobes as smoking affects upper lobes.
Pan-acinar (damage to whole acinus distal to resp bronchioles) - due to a1 anti-trypsin deficiency. More severe in lower lobes.
Leads to loss of elastic coil of alveolar sacs and airway collapse on expiration - airway trapping and hyperinflation
Decreased SA for gas exchange
Goblet cell hyperplasia, mucus plugging of lumen, inflammation of airway wall, smooth muscle hypertrophy of bronchial wall and fibrosis
COPD signs on CXR
Heart is long and thin
More ribs seen
Hemi diaphraghms are flattened
Assessing risk of exacerbations
Severity of symptoms and breathlessness
and
Severity of airflow limitation
Treatment COPD
Group A
Bronchodilator
Group B
LAMA or LABA
Group C
- LAMA
- LAMA + LABA
Group D
- LAMA + LABA
- LAMA + LABA + ICS (budesonide)
- Roflumilast or Azithromycin
SABA: salbutamol
SAMA: ipatropium bromide
LABA: salmetarol
LAMA: tiotropium
Roflumilast (phosphodiesterase inhibitor 4) - Increases intracellular cAMP, decreasing pro-inflammtory cytokines)
Azithromycin: anti- inflammatory
Carbocisteine - mucolytic, decreases sputum viscosity
Respiratory failure
Blue bloater
Type 2 resp failure
Low PO2, high PCO2
Cyanosis
R sided HF
oedema, raised JVP
Confusion
Pink puffer
Type 1 resp failure
Low PO2, low PCO2
Desaturates on exercise
Uses accessory muscles
Wheeze
Breathless
Allergy
Clinical reaction based on immunological tolerance
Requires trigger, memory and produces certain clinical features depending on which part of the immune system is activated
Upon first exposire:
IL4, IL-33 leads to activation of IgE on mast cells (immediate)
When re-exposed:
IL-12, IFN leads to activation of reactive T cell (delayed)
Chronic allergy leads to tissue remodelling
Allergy vs hyperreactivity
Hyper-reactivity: exagerated but physiological process. Dose dependent effect.
Allergy - occurs no matter the dose of stimulus
Asthma (definition/symptoms, pathophys)
Chronic inflammatory condition characterised by recurrent wheeze, breathlessness, chest tightness and cough. Assoc. with bronchoconstriction which is reversible
Patholgical features:
Muscus plugging
Smooth muscle hypertrophy
Increased airway inflammatory cells
Pathophysiology:
Immediate asthma (starts in mins, subsides in hour)
- bronchoconstriction triggered by direct stimulation of subepithelial vagal receptors, increased mucus production
Late phase:
Follows immediate reaction, sustained airflow limitation
Inflammtion with recruitment of eosinophils, neutrophils, CD4 T cells
Inflammtory cells involved:
CD4 T helper cells: IL-4 (stimulates IgE), IL-5 (stimulates eosinphils), IL-13 (mucus secretion) - maintains allergic phenotype
Eosinophils - attracted to airways by IL-5, chemokines. Release LTC4 (leukotrienes) when activated
Mast cells - increaesd in mucus glands, produce histamine, leukotrienes
Mediators in late phase
Leukotrienes - bronchoconstriction, mucus secretion
histamine - bronchoconstriction
prostaglandins - bronchoconstriction, vasodilation
Airway remodelling in chronic asthma:
Thickening of airway wall
Epithelium - loss of ciliated columnar cells, increased no. of mucus secreeting goblet cells
Smooth muscle hypertrophy
Th1 cells, TNF-a involved
Extrinsic allergic alveolitis (hypersensitivity pneumonitis)
Immunological mediated iflammation of alveoli and resp. bronchioles due to inhaled substances
T cell mediated repsonse
Causes:
- Farmer’s lung (moudly hay)
- Bird fancier’s lung (due to bird dander)
Symptoms: flu-like illness, cough, high fever (4-8 hrs after exposure)
Chronic: dyspnea, sputum, weight loss
Investigations:
Avian precipitans, aspergillus precipitans
Acute:
4-6 hrs after exposure
Wheeze, cough, fever, headache
Type III hypersensitivity - antibody binds to antigen of trigger and forms immune complexes leading to inflammation
Leads to filling of alveoli with fluid - loss of O2
Sub-acute:
Type IV T cell mediated hypersensitivity
Chronic exposure leads to - pulmonary fibrosis (scarring due to tissue remodelling) and emphysema (interstitial destruction due to neutrophil enzyme release)
Microscopy: Bronchiolocentric pattern, Non-nec granulotamous inflammtion, foamy macrophages
Leads to decreaed passive diffusion between alveoli and blood vessel leading to decrease O2 transport and airspace shadowing on CXR
Management:
Avoid trigger
Corticostreroids
Causes of asthma
Atopic (extrinsic) asthma - usually starts in childhood
- increased IgE
Non-atopic (intrinsic) - starts in middle aged, due to resp viruses, pollutants
Enviromental - hygeine hypothesis. Clean environment predisposes immune system to allergy/T helper cell repsonse. Bacteria predisposes immune system to TH1.
Triggers:
Environmental exposure: house dust mite
Occupational: non Ig E related: isocynates
Ig E related: latex
Irritants: perfume
Cold weather
Genetics: IL4/13
Allergen induced asthma (immediate and late phase)
Immediate asthma (starts in mins)
bronchoconstriction triggered by direct stimulation of vagal receptors, increased mucus production
Late-phase
Sustained airflow limitation
inflammation with recruitment of esoinophils, neutrophils, lymphocytes
Cells and immune mediators involved in asthma
Cells:
CD4 T helper cells
Eosinophils
Mast cells
Immune mediators
Leukotrienes
Histamine
Ach
Prostaglandins
Asthma treatment: Corticosteroids
Budesonide
Binds to activated glucocorticosteroid receptors to supress multiple pro-inflammatory cytokines that are activated in asthmatic airways
Up-regulates B2-adrenoceptors in airways
Indications: Asthma, COPD
Side effects: OP, cushing’s syndrome, immune suppression, thrush
Other points: Increase dose during illness, carry steroid card
Bronchodilators, muscarinics, methylxanthines
B2 agonist:
Short acting B2 adrenoceptor agonist
- Relaxes bronchial smooth muscle, causing bronchodilation
- Inhibits pro-inf cytokines from mast cells decreasing airway inflammation
- Stimulates cilia action, increasing mucus clearence
Side effects: tremor, arrythmias, tachycardia, hypokalaemia
SABA: salbutamol, terbutaline
LABA: salmeterol, fometerol
Muscarinics:
Inhibits muscarinic (M1 and M3) receptors in lung leading to decreased parasympathetic mediated bronchoconstriction
Reduces mucus secretion.
Side effects: blurred vision, urinary retention, dry mouth
SAMA: ipotropium bromide
LAMA: tiotropium
Methylxanthines:
Theophylline, Aminophylline
Phosphodiesterase inhibitor - bronchial smooth muscle relaxation
Improves mucociliary clearence
Side effects: hypokalaemia, arrthymias, narrow therapeutic window
Indicated: adjunct to inhaled therapy in asthma, IV for severe exacebations
Leukotriene inhibitors
Montekulast
Inhibits LTD4 (leukotriene D4) in smooth muscle cells in airways and airway macrophages leading to smooth muscle relaxation and decreased oedema
Indicated: exercise induced asthma
Monoclonal treatments for asthma
Omalizumab
Anti-IgE antibody
For persistent, severe asthma
Side effects: hypersensitivity
Mepolizumab
Anti-IL5 antibody
Reduces eosinophils
Side effects: headache
Both given sub cut
Stepwise treatment of asthma
Step 1: Short acting B2 agonist (salbutamol)
Step 2: + ICS (Budesonide)
Step 3: LABA (salmeterol) + ICS
Add LRTA (Montekulast) or theophylline or oral B2 agonist
Step 4: high dose ICS + regular bronchodilator e.g. nebs, anti-muscarinics
Step 5: Steroid tablet
Omalizumbab (anti-IgE), Mepolizumab (anti-IL-5), Entanercept (Anti-TNFa)
Asthma vs COPD (symp, investigations, treatment for exacerbations)
Asthma
Symptoms:
Recurring cough, wheeze, chest pain, breathlessness esp in night/early morning
Investigations:
FBC (raised eosinophils), CRP, Uand Es
Sputum (esoinophils)
PEFR
Spirometry - obstructive, imrpoves >400mL and 15% FEV1 after broncholdilator
CXR - may have pneumothorax
sputum culture - resp. viruses
ABG
Treatment for acute exacerbation
40-60% O2 aim >94% sats
Salbutamol and ipatropium bromide nebs
Prednisolone
Life threatning:
IV Mg
IV salbutamol
If pt improving:
40-60% O2, prednisolone (at least 5 days), nebs salbutamol and ipatropium
Cell type involved:
CD4 T cells (secrete IL-4, 5, 13), eosinophils, mast cells
COPD
Symptoms:
Chronic cough, sputum production, wheeze, exertional breathlessness
Investigations:
FBC (polycythaemia (increased Hb) if chronic hypoxaemia), CRP, U and Es
Sputum culture, viral gargle
Spirometry - obstructive. Little improvement after bronchodilator
CXR - hyperinflation, consolidation
Alpha 1 anti-trypsin genetic test
ABG
Treatment acute exacerbation:
24-28% O2, aim 88-92% sats
Salbutamol and ipatropium bromide nebs
Prednisolone
Antibiotics if bacterial infection e.g. purulent sputum - amoxilicillin
Non-invasive ventilation: for acidotic type II resp failiure
Cell types involved:
CD8 T cells, macrophages, neutrophils
Pleural effusion
Fluid in pleural space
Clinical signs: decreased breath sounds, stony dull to percussion, decreased vocal fremitus
CXR appearence pleural effusion vs pneumothorax
Pleural effusion
>300mL fluid
Generally white appearence
Blunting of costophrenic angles
Mesnicus at upper edge
Mediastinal shift away
Pneumothorax
Pleural line
Hyperlucent (dark) lung
Tracheal deviation away from affected side
Depression of hemidiapragm
Pleural effusion vs pneumothorax
Pleural effusion
Accumulation of fluid in pleural cavity
Symptoms:
SOB, pleuritic chest pain, referred pain to shoulder and abdomen
Signs:
Reduced breath sounds, stony dull percussion, reduced vocal fremitus, pleural rub
Causes:
Transudative:
Cardiac failure (increased hydrostatic pressure)
Cirrhosis, hypoalbuminaemia/nephrotic syndrome (decreased oncotic pressure)
Exudative:
Pneumonia (increased vascular permeability), malignancy (decresed lymphatic drainage), TB
Investigations:
Exam, history, CXR - transudate? - treat
If not, pleural aspiration (with US).
Transudate <30 protein, <2/3 LDH ULN, clear, bilateral
Exudate >30 protein, >2/3 LDH ULN, cloudy, unilateral
Pneumothorax
Air in pleural cavity
Breach in pleural cavity leads to collapse of lung
Causes:
Traumatic - rib fracture
Iatrogenic - aspiration, pleural biopsy
Spontaenous - primary (fit, healthy, development subpleural blebs which ruptures and tears visceral pleura leading to lung collapse.
- secondary (underlying lung disease e.g. COPD - weakness in lung tissue, CF. asthma (increased airway pressure)
Symptoms: SOB, pleuritic chest pain, resp distress
Signs:
Decreased vocal resonance, hyper-resonant to percussion, tracheal deviation if tension pneumo
Investigations:
Observe (via CXR) if small or asymptomatic
Aspiration (if >2cm in primary, or 1-2cm in secondary)
Intercostal chest drain (if >2cm in secondary)
VATS (video assisted transthoracic surgery)
Talc pleurodesis
Tension pneumo:
Medical emergency
One way valve, air enters pleural space but doesn’t leave
Decreased venous return, CO, BP
Treatment: aspiration, chest drain
Empyema
Pus in pleural cavity
Treatment: IV antibiotics, DVT prophylaxis, fibrinolytics
Mesothelioma
Pirmary tumour of pleura, due to asbestos exposure
Epitheliod or sarcomatoid appearence
Adenocarcinoma genetic testing and treatments
EGFR inhibitors:
Erlotinib
Cetuximab
Nivolumab - inhibits PD-L1 (receptor on tumour which binds to PD1 on T cells, stopping T cell from killing it)
ALK: Crizotinib
Inhibits ALK which inhibits EML4 ALK- fusion gene (leads to activation of tyrosine kinase, lead to cell proliferation)
Lung cancer
Symptoms: cough, haemoptysis, weight loss, SOB, chest pain
Signs: finger clubbing, pleural effusion, from metastases - cervical lymphadenopathy, cahexia, Horner’s syndrome (Pancoast tumor), Cushingoid, oedema in face/arm (SVC obstruction)
Small cell carcinoma
- Chemotherapy, radiotherapy, no surgery
Aggressive
Central
Appearence: small oval/spindle shaped cells, nuclear moudling, scant cytoplasm, finely granular nuclear chromatin (salt and pepper pattern)
Limited or extensive
Non-small cell carcicnoma
Sugery
Radiotherapy
Chemo
Squamous cell carcnioma
Central
Keratinized, intercellular bridges
Can secrete PTHrP
- p53
Adenocarcinoma
Periphary
TTF-1 (thyroid transcription factor) positive
Glandular, mucin production
Most common in female smokers, and non-smokers
If EGFR +ve, can give EGFR inhibitors
Large cell carcinoma
Diagnosis of exclusion
Undifferentiated malignant epithelial tumour with no features of small cell, squamous or adenocarcinoma
Usually central
Carcinoid
Well diferentiated neuroendocrine tumour
Better prognosis
Yellow-brown tumor
Other treatments:
Endobronchial lasers/stents
Palliative
Differentials pulmonary nodules and masses
Malignant
Bronchial carcinoma
Metastases
Benign:
Abcess
TB
Sarcoidosis
What does the mediastinum consist of?
Blood vessels, trachea, oesophagus, thymus, thoracic duct, phrenic nerves
Bilateral hilar adenopathy
TB
Sarcoidosis
Lyphoma
Malignancy
UL collapse
Suspect malignancy
Also be mucus plug, foreign body
Golden reverse S sign
Left lower lobe collapse
Sail boat sign
Can’t see left hemidiaphragm
Remainig left lung is hyperlucent (dark)
Causes of opacification (white) lung
Mediastinum central:
Pleural effusion
Consolidation
Mediastinum towards:
Collapse
Pneumectomy
Mediastinum away:
Pleural effusion
Common non-metastatic manifestation lung cancer
Weight loss
Hypercalcaemia - increased PTHrP
Cushing’s - increased ACTH
SIADH - increased ADH
Eaton-Lambert syndrome
Finger clubbing
Emergency condition assoc. with lung cancer
SC compression
Symptoms: leg weakness, reduced bladder/bowel control
Signs: upper motor neuron signs in legs
Treatment: high dose steroids, radiotherapy
SVC obstruction
Symptoms: oedema in face/arms, breathless
Signs: raised JVP, dilated veins in arms
Treatment: high dose steroids, radiotherapy/chemo
Interstitial lung disease
Unknown
Sarcoidosis
Idiopathic pulmonary fibrosis
Known
Occupation: Asbestos
Drugs: Nitrofurantoin, methotrexate, cocaine
Environment: Hypersensitivity pneumonitis
Connective tissue diseaes: RA, Lupus
Sarcoidosis
Multi-system inflammatory disease of unknown cause, mostly of lungs and intrathoracic lymph nodes. Diagnosis of exclusion. Characterised by non-necrotising granulomatous inflammation
Causes: Borrelia Burgdorferi, TB
Symptoms:
fever, weight loss, night sweats,
SOB on exertion, cough, chest pain
Diagnosis:
FBC (anaemia), LFTs (AST/ALT high)Ca (high), serum ACE (high)
CXR:
Stage 1: Bilateral lymphadenopathy without hilar infiltration
Stage 2: Bilateral lymphadenopathy with hilar infiltration
Stage 3: infiltration
Stage 4: fibrotic bands, bullae
Idiopathic pulmonary fibrosis (IPF)
Form of chornic fibrosing interstital pneumonia of unknown aetiology. Characterised by scar tissue in lungs and progressive dyspnoea.
Symptoms: progressive breatlessness, cough, bilateral crackles
Signs: weight loss, finger clubbing
Complications: cor pulmonale
Causes: Abestos, methotrexate, amiodarone, lupus, RA, sarcoid, idiopathic
Diagnosis:
Made by clinical diagnosis, with restrictive pattern and XR changes
Spirometry - restrictive diseasse (both FEV1 and FVC reduced, TLC reduced, CO gas transfer reduced)
ABG (type I resp failure)
CXR: basilar reticular opacities
High Res CT - subpleural reticular abnormalities, honey combing - thick walled cysts in bronchioles
Lung biospy - temporal heterogenity: areas of fibrosis and healthy tissue
fibroblastic foci
Macroscopically - fibrotic areas of lung - firm, rubbery, white
Pathogenesis:
Agent leads to abnormal activation of epithelial cells - abnormal repair - inflammation - formation of fibroblastic foci
Cell types involved:
Damaged epithelial cells - release TGFB1
Fibroblasts - secrete collagen
Type I pneumocytes reduced
MUC5B gene assoc with familial IPF
Treatment
Pirfenidone: anti fibrotic, anti-inflammatory
Nintedenib: inhiibtor of tyrosine kinases
Long term O2, antibiotics, lung transplant
Obstructive sleep apnoea
Obstructive sleep apnoea
Recurreing partial/complete airway obstruction during sleeping, leading to intermittent hypoxia
OSAS - daytime sleepliness
Symptoms:
Snoring, daytime sleepliness, fatigue, disruptive sleep, witness apnoeas
Assessment:
History (and from partner), BMI, BP, Neck circumference, craniofacial appearences
Epsworth sleepiness score
Investigations
Limited sleep polysomnography
Full polysomnography
Apnoea-hypoapnoea index: no. of apnoeas (stopping of airflow) and hypoapnoeas (reduced airflow) divded by total hrs slept
AHI >15 = diagnositc OSA
Oxygen desaturation index:
no. of times per hour that SpO2 >4% drop below baseline
Treatment:
Weight lossReduce triggers e.g. alcohol
CPAP - mask over nose directs air in, keeps airway open
Mandicbular advancement device
Sleep position traineres - vibration when pt on back to change position - for supine OSA
Untreated OSAS
Increased risk of CVA
Accidents at work
RTA
Need to inform DVLA
(if without daytime sleepiness, can still drive)
Lung cancer investigations
FBC, CRP, LFTs, UEs
CXR
CT chest and upper abdomen - look for mets
Bronchoscopy (endoscope to see airway)
Others:
US guided aspiration biopsy of supraclavicular lymph nodes
CT-PET - look for mets
Aim of investigations:
To diagnose - whether small cell or non small cell
To stage
To assess fitness for treatment
Investigations to assess fitness for lung cancer?
Lung function tests
FEV1 > 1.5L
ECG, echo - cardiac disease
Common sites of metastasis of lung ca.
Lymph nodes - mediastinal (obstructs SVC), cerivcal
Liver
Bone - can cause SC compression
None metastatic manisfestation of lung ca.
Metabolic
Endocrine
- ectopic ACTH (Cushing’s)
- ectopic ADH - water retention - hyponatraemia (sIADH)
- PTHrP (hypercalcaemia)
Neuro - Lambert-Eaton Syndrome
Lung ca emergencies
Spinal cord compression
Symptoms: leg weakness and numbness, incontinence
Signs: UMN signs in legs
SVC obstruction
- due to mediastinal nodes, compressing SVC
Symptoms: SOB, oedema in face and arms
Signs: Raised JVP
Treatment: high dose steroids
Type I and type II resp failure
Type 2 resp failure “blue bloater” - loss of CO2 sensitivity rely on hypoxic drive to stimulate breathing
Low resp drive, Low PaO2 and high PaCO2
cyanosis, flapping tremor, oedema, right sided heart failure
Type 1 resp failure “pink puffer”
High resp drive, decreased PaO2 and Pa CO2
Weight loss, pursed lip breathing, use accessory muscles,
Long term COPD therapy
MRC Dyspnoea scale (assesses level of breathlessness) used to assess prognosis
Other: smoking cessation, pulmonary rehabilitation, vaccinations (influenza, pneumococcus)
Long term O2 therapy:
In COPD pts who have
PaO2 < 7.3
or 7.3 - 8 AND pulmonary oedema, pulmonary hyptertension
and non-smokers for 3 months
Resp failure: PaO2 < 8kPa on room air (21%)
Asthma (moderate exacerbation, acute severe, life threatning, near fatal)
Mod exacerbation
Increasing symptoms
Acute Severe
RR >25
HR> 110
Inabiliy to complete sentences in one breathe
Life threatning
PEF <33%
Normal PaCO2
Near fatal
Raised PaCO2 and/or requires mechiancal ventilation
COPD exacerbation definition
Sustained worsening of pts symptoms from usual, stable state and acute onset. Common symptoms: worsening breathlessness, increased sputum production, change in sputum colour.
Change in symptoms ususally needs change in medication
Insterstial lung disease investigations
FBC, UEs, LFTs, ESR (raised in 1st hr), CRP (normal)
Immunology
ANA
ANCA
Serum ACE (sarcoidosis)
Serum immunoglobulins (raised in active sarcoid)
ABG - type 1 resp. failure
- due to V/Q mismatch
PaCO2 normal or low (due to hypoventilation)
Six minute walk test - test desaturation
Echo - pulm hypertension
CXR - ground glass changes (increased hazy areas in lung due to alveolar wall inflammation, visible bronchial markings), irregular reticulonodular shadowing
CT - subpleural abnormalities
honeycombing (thick walled cysts in resp bronchioles)
