Week 8 Flashcards
What is the definition of COPD?
airlflow obstruction which is usually progressive, not fully reversible and does not change markedly over several months
the disease is commonly caused by smoking
Describe the effects of cigarette smoking on the lungs
cilial motility is reduced
airway inflammation
mucous hypertrophy and hypertrophy of goblet cells
increased protease activity, anti-proteases inhibited
oxidative stress
squamous metaplasia - higher risk of lung cancer
Describe alpha 1 anti-trypin deficiency
present in 1-3% COPD patients
serine proteinase inhibitor
M alleles normal variant
SS and ZZ homozygous have clinical disease
unable to counterbalance destructive enzymes in the lung
non smokers get emphysema in 30s-40s
smokers get it mu earlier
What are the 2 main aspects of COPD?
chronic bronchitis
emphysema
Describe chronic bronchitis
the production of sputum on most days for at leaser 3 months in at least 2 years
Describe emphysema
abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles
Describe the pathophysiology of chronic bronchitis
infiltration with neutrophils and CD8+ lymphocytes squamous metaplasia loss of interstitial support increased epithelial mucous cells mucous gland hyperplasai
Describe bronchiolitis
small airways disease
may be an early feature of COPD
narrowing of bronchioles due to mucous plugging, inflammation and fibrosis
What cells are principally involved in COPD inflammation?
macrophages
CD8+ and CD4+ lymphocytes
neutrophils
What inflammatory mediators are involved in COPD inflammation?
TNF, IL-8 and other chemokines
neutrophil elastase, proteinase 3, cathepsin G
elastase and MMPs (form macrophages)
reactive oxygen species
What are the 2 main types of emphysema?
centri macinar and pan acinar
Describe centri-acinar emphysema
damage around the respiratory bronchioles
more in upper lobes
Describe pan -acinar emphysema
uniformly enlarged from the level of terminal bronchiole distally
can get large bull
associated with alpha 1 anti-trypsin deficiency
What are the mechanisms of airflow obstruction in COPD
loss of elasticity and alveolar attachments due to emphysema - airways collapse on expiration
causes air trapping and hyperinflation - increased work of breathing, breathlessness
goblet cell metaplasia and mucous plugging of lumen
inflammation of airway wall
thickening of bronchiolar wall - smooth muscle hypertrophy and peribronchial fibrosis
What are the changes in a chest X-ray in COPD?
hyperinflation of the lungs trapping of air in peripheries flattening of diaphragm heart appears small and thin lungs look blacker - loss of blood vessels
When should the diagnosis of COPD be considered?
those who are over 35, smokers or ex-smokers, with any of: exertional breathlessness chronic cough regular sputum production frequent winter bronchitis wheeze
Describe spirometry of COPD
FEV1/FVC ration <70% FEV1 at each stage 1(mild) - 80% 2(moderate) - 50-79% 3(severe) - 30-49% 4(very severe) - <30%
What are the treatments of COPD?
inhaled bronchodilators inhaled corticosteroids oral theophylline mucolytics - carbocysteine nebulised therapy
What types of inhaled bronchodilators are there?
short acting - salbutamol
long acting - salmeterol, tiotropium
What types of inhaled corticosteroids are there?
budesonide and fluticasone - combination inhalers
Describe a blue bloater
low respiratory drive type 2 respiratory failure low O2, high CO2 cyanosis warm peripheries bounding pulse flapping tremor confusion, drowsiness right heart failure oedema, raised JVP
Describe a pink puffer
high respiratory drive type 1 respiratory drive O2 and CO2 down desaturates on exercise pursed lip breathing use accessory muscles wheeze indrawing of intercostals tachypnoea
What are involved in asthmatic airway inflammation?
CD4+
T lymphocytes
eosinophils
What is the primary derangement in metabolic acidosis and what is the compensation?
Low HCO3
low CO2
What is the primary derangement in metabolic alkalosis and what is the compensation?
high HCO3
high CO2
What is the primary derangement in respiratory acidosis and what is the compensation?
high CO2
may be high HCO3
What is the primary derangement in respiratory alkalosis and what is the compensation?
low CO2
may be low HCO3
What is compensation?
attempt to restore the correct acid-base balance
What are the main buffers in acid-base balance?
haemoglobin
plasma proteins
bicarbonate
phosphate
When should you suspect a mixed acid-base disorder?
inadequate or extreme compensation
CO2 and HCO3 become abnormal in the opposite direction
the pH is normal but CO2 and HCO3 is abnormal
What does it mean if the PCO2 is high and the HCO3 is low?
respiratory and metabolic acidosis
What does it mean id PCO2 is low and HCO3 is high?
respiratory and metabolic alkalosis
What is the normal range for H+?
35-45
What is the normal range for PCO2?
4.5-5.6
What is the normal range for PO2?
12-15
How is the anion gap calculated?
sodium - (chloride +bicarb)
What is the normal anion gap?
8-16
What are the causes of metabolic acidosis with raised anion gap?
renal failure
diabetic or other ketoacidosis
lactic acidosis
toxins - salicylate, methanol
What are the causes of metabolic acidosis with normal anion gap?
renal tubular acidosis
diarrhoea
carbonic anhydrase inhibitors
ureteric diversion
How is the osmolal gap calculated?
measured osmolality-calculated osmolality
How is osmolality calculated?
2X(sodium and potassium) + urea +glucose (all in mol/L
What is the normal OG?
<10mOsm/kg
Describe non-invasive ventilation in COPD
provides positive pressure to the airways to support breathing
recommended as the first line intervention in addition to usual medical care in COPD exacerbations with persistent hypercapnia respiratory failure
considered if there is a respiratory acidosis present or persists despite maximum medical therapy
What is cor pulmonale?
right heart failure secondary to lung disease
salt and water retention leading to peripheral oedema
What are the signs of cor pulmonale?
peripheral oedema raise JVP systolic parasternal heave loud pulmonary second heart sound pulmonary hypertension and right ventricular hypertrophy may develop
What is the treatment of cor pulmonale?
diuretics
Why do we measure lung function?
evaluation of the breathless patient
lung cancer - fitness for treatment
pre-operative assessment
disease progression and treatment response
monitoring of drug treatment toxic to the lungs
pulmonary complications of systemic disease
What is spirometry?
forced expiratory manoeuvre from total lung capacity followed by flu inspiration
What are the pitfall of spirometry?
appropriately trained technician
effort and technique dependent
patient frailty
pain, patient too unwell
Describe obstructive lung disease
generally asthma or COPD
FEV1/FVC ratio <70%
Describe reversibility testing in obstructive lung disease
nebulised or inhaled salbutamol given
spirometry before and 15 min after salbutamol
15% and 400mL reversibility of FEV1 suggestive of asthma
What other investigations can be used in asthma?
PEFR testing - diurnal variation and variation over time
bronchial provocation
spirometry before and after trial of inhaled/ oral corticosteroid
Describe restrictive lung disease
FEV1 and FVC reduced
FEV1/FVC ratio >70%
What can cause restrictive spirometry?
interstitial lung disease kyphoscoliosis/ chest wall abnormality previous pneumonectomy neuromuscular disease obesity poor effort/technique
Describe transfer factor
single breath of very small concentration of CO
high affinity to Hb
measure concentration in expired gas to derive uptake upon lungs
What is transfer factor affected by?
alveolar surface area
pulmonary capillary blood volume
haemoglobin concentration
ventilation perfusion mismatch
What is transfer factor reduced in?
emphysema
interstitial lung disease
pulmonary vascular disease
anaemia (increased in polycytaemia)
How can lung volumes be measured?
helium dilution (inspire known quantity of inert gas) body plethysmography (respiratory manoeuvres in a seal box lead to changed in air pressure - can derive lung volumes
What is oximetry?
non-invasive measurement of saturation of Hb by oxygen
depends of oxyhemoglobin and deoxyhaemoglobin absorbing infrared differently
Does not measure carbon dioxide so no measurement of ventilation
false reassurance in a patient on oxygen with normal Sats
What are the main causes of hypoxaemia?
hypoventilation
ventilation/perfusion mismatch
shunt
low inspired oxygen
Describe VQ mismatch
main cause of hypoxaemia in medical patients
read of the lung that are perfused but not well ventilated
mixing of blood from poorly ventilated and well ventilated parts of the lung cause hypoxaemia
does not fully correct with oxygen administration
Describe extra-thoracic disease
not susceptible to intra-thoracic pressure for example laryngeal oedema stridor flow-volume loops aspiration to right middle/lower lobe
What are the clinical consequences of bronchial disease
medium - small airways flaccid walls- not supported by cartilage, expiratory phase narrowing (wheeze)
much-ciliary clearance impairment - sputum
characteristic flow volume loops
What is the clinical definition of asthma?
appropriate symptoms with signs - wheeze, cough, yellow/clear sputum
breathlessness, exercise intolerance
episodic, triggered, variable - paroxysmal - exercise, cats, chemicals
diurnal -nocturnal awakening
respond to asthma therapies
What is the physiological definition of asthma?
reversible airflow obstruction
airways hyper-responsiveness
What cytokines are overproduced in asthmatic airways ?
IL5 TSLP IL13 TNFalpha TGFbeta VEGF
What are the main cells involved in asthma?
mast cells
lympohcyes
macrophages
epithelial cells
What airway remodelling can occur in chronic asthma?
angiogenesis
epithelial cell damage
fibrosis
smooth muscle hypertrophy
Describe the acute illness of allergic disease in the lung parenchyma
4-6 hours after exposure
wheeze, cough, fever, chills, headache, myalgia, malaise fatigue
may last several days
serum sickness illness
What are the clinical consequences of allergic disease in the lung parenchyma?
thickening of septae, filling of the alveolus with fluid
loss of O2 - hypoxaemia (normal Co2)
airspace shadowing on CXR
What can chronic exposure in allergic disease of the lung parenchyma lead to?
fibrosis - interstitial scarring from chronic tissue remodelling - repair pathways
emphysema- interstirtial destruction from neutrophilic enzyme release
Describe extrinsic allergic alveolitis
acute illness due to type III reaction
sub acute days to weeks
type IV- t cell mediated reactions
chronic disease - fibrosis and emphysema
What is the treatment of extrinsic allergic alveoli’s?
avoid trigger
corticosteroids
oxygen supplementation
What is obstructive sleep apnoea?
recurrent episodes of partial or complete upper airway obstruction during sleep, intermittent hypoxia and sleep fragmentation
What is obstructive sleep apnoea syndrome?
manifests as excessive daytime sleepiness
What are the symptoms of obstructive sleep apnoea?
snorer witnessed apnoeas unrefreshed sleep daytime somnolence fatigue/low mood/poor concentration
How is OSA assessed?
history - from partner weight BMI BP neck circumference craniofacial appearance tonsils nasal patency
What is involved in limited polysomnography?
5 channel home study oxygen Sats heart rate flow thoracic and abdominal effort position
What is involved in full polysomnography?
EEG video audio thoracic and abdominal bands position flow oxygen sats limb leads snore
What are the advantages of full PSG?
correct patient
accurate assessment of sleep effiency
sleep staging via EEG
parasomnic activity - acting out dreams, sleep talking
What is apnea?
the cessation or near cessation of airlflow
4% oxygen desaturation lasting >4secondsa
What is hypopnea?
a reduction of airflow to a degree insufficient to meet the criteria for an apnoae
What are respiratory effort related arousals?
arousals associated with a change in airflow that does not meet the criteria for apnoea or hypopnoea
What is the apnoea-hypopnea index?
the number of apnoeas and hypopnoeas per hour
What is the oxygen desaturation index?
the number of times per hour that the SpO2 falls atlas 4% from baseline
What is the diagnostic criteria for AHI in OSA?
> 15 is diagnostic
5-15 with compatible symptoms
What is the treatment of OSAS?
explanation
weight loss
avoid triggers - alchohol
treat underlying conditions - tonsils, hypothyroidism, nasal obstruction
What does CPAP do?
splints airway open
stops snoring
stops sleep fragmentation
What can untreated OSAS lead to?
hypertension right heart strain cardiovascular disease increased risk of CVA increased accidents at work poor concentration increased road traffic accidents
Describe OSAS and driving
without daytime somnolence - no need to stop driving
inform DVLA is OSAS
can hold licence if compliant with treatment and reduced DTS
cat 2 licence require ongoing monitoring by DVLA
What is a pneumothorax?
air within the pleural cavity
What types of pneumothorax are there?
traumatic, iatrogenic, spontaneous
What can cause a traumatic pneumothorax?
stabbing
fractured rib
What can cause an iatrogenic pneumothorax?
CT guided lung biopsy
TBLB
pleural aspiration
What can cause a spontaneous pneumothorax?
primary - young patient, no underlying lung disease
secondary, underlying disease (COPD, cystic fibrosis)
Describe a tension pneumothorax
medical emergency
one way valve leads to increased intrapleural pressure
venous return impaired, cardiac output and blood pressure fall
PEA arrest without intervention
What is the immediate management of a tension pneumothorax?
insert venflon 2nd intercostal space mid-clavicular line to relieve pressure
What is the pathophysiology of primary pneumothorax?
development of subpleural blebs/bullae at lung apex
possible additional diffuse, microscopic emphysema below the surface of the visceral pleura
spontaneous rupture leads to tear in visceral pleura
air flows from the airways to pleural space
elastic lung then collapses
Describe the pathophysiology of secondary pneumothorax
inherent weakness in lung tissue
increased airway pressure
increased lung elasticity
patient is generally much more symptomatic
management more complex, prognosis less good
What are the symptoms and signs of pneumothorax?
pleuritic chest pain breathlessness respiratory distress reduced air entry on affected side hyper-resonance to percussion reduced vocal resonance tracheal deviation if tension
What is the differential diagnosis of pneumothorax?
PTE
musculoskeletal pain
pleurisy/ pneumonia
What are the management options of pneumothorax?
observation (serial CXR) if small or not very symptomatic
aspiration
intercostal drain with underwater seal
What can be done to treat a pneumothorax if a drain fails to work?
VATS (video assisted thoracic surgery)
can stable blebs
talk pleurodeses
pleural abrasion / stripping
What are the clinical predisposing risk factors of PE?
surgery <12 weeks previously immobilisation >3 days in previous 4 weeks previous DVT/ PTE or family history lower limb fracture pregnancy or postpartum long distance travel oestrogen containing OCP use
What are the symptoms of PE?
pleuritic chest pain dyspnoea cough haemoptysis syncope
What are the signs of PE?
tachypnoea crackles tachycardia fever signs of peripheral DVT
What are the acute changes in the pathophysiology of PE?
anatomical obstruction of pulmonary vascular bed
increased pulmonary vascular resistance
right ventricular strain
reduced mixed venous oxygen content, right to left shunting through PFO
increase in alveolar-arterial gradient. hypoxaemia in large PTE
What are the investigations for PE?
risk assessment - modified geneva D -dimer arterial blood gases - troponin level ECH echocardiogram radiology - CXR, CT pulmonary angiogram, V/Q scan
What is expected to be seen in the arterial blood gases in a PE?
usually respiratory alkalosis
hypoxaemia only seen with large PE
Why is an echocardiogram used in investigation of PE?
to look for RV strain
What is the treatment of massive pulmonary embolism?
unfractionated heparin IV
fluid resuscitation
thrombolysis with alteplase if fails to improve
What is a massive pulmonary embolism?
PE associated with a systolic BP <90 or a drop of systolic BP >40 mmHg in <15 minutes
What is the treatment of sub-massive PE?
low molecular weight heparin -dalterparin
oral anti-coagulation for 3 months
factor Xa inhibitors
warfarin
What is sarcoidosis?
a multisystem inflammatory disease of unknown ethology that predominantly affects the lungs and intrathoracic lymph nodes. Characterised by non necrotising granulomatous inflammation
What can be the presentation of sarcoidosis?
fever anorexia fatigue night sweats weight loss dyspnoea cough chest pain haemoptysis
Describe idiopathic pulmonary fibrosis
age >50 M:F 2:1 progressive breathlessness bibasilar crackles, clubbing peripheral interstitial pattern subpleural honeycombing
What are the symptoms of IPF?
breathlessness hacking dry cough fatigue and weakness appetite and weight loss clubbing
What are the causes of pulmonary fibrosis?
occupation and environmental drug induced connective tissue diseases primary disease idiopathic genetics
What are the occupational and environmental causes of PF?
silicosis
asbestosis
hypersensitivity pneumonitis
What are the drugs which can cause PF?
amioderone
nitrofurantoin
methotrexate
cocaine
What are the connective tissue diseases that can cause PF?
lupus
RA
scleroderma
What are the primary diseases that can cause PF?
sarcoidosis
LAM
How is PF diagnosed?
HRCT
What is hypersensitivity pneumonitis?
immunologically mediated inflammatory reaction in the alveoli and in the respiratory bronchioles
T cell mediated response
causes - dusts, moulds, foreign proteins (animals), some chemicals
What are the symptoms of hypersensitivity pneumonitis?
flu like illness cough fever, chills dyspnea chest tightness malaise myalgia chronic - dyspnea in strain, sputum production, fatigue, anorexia, weight loss
What is the appearance of acute HSP on CXR?
numerous poorly defined small opacities in both lungs
sometimes sparing of the apices and bases
ground glass opacities
fine reticulation
zonal distribution
Describe the pathology in chronic HSP
bronchocentric pattern
foamy macrophages in alveolar spaces
chronic interstitial inflammation
organising pneumonia
What are the risk factors of lung cancer?
smoking environmental tobacco smoke ionising radiation - radon air pollution asbestos fibrosing conditions of lung, HPV, hereditary
Describe the pathogenesis of lung cancer
multi step
chronic irrigation/ stimulation of cells by carcinogens
increased cell turnover
progressive accumulation of genetic abnormalities in molecules involved in cel cycle, signalling and angiogenesis pathways
phenotypic changes potentially reversible (but genotypic alterations persist)
What are some of the targets of new targeted therapies of lung cancer?
EGFR
ALK
PD-L1
What are the signs and symptoms of lung cancer?
cough
haemoptysis
chest pain
metastases
Describe the local spread of lung cancer
mediastinum - SVC obstruction, recurrent laryngeal nerve, phrenic nerve
pancoast tumour - brachial plexus, horner’s syndrome
where do lung cancers typically spread to?
liver, lymph nodes, bone, brain, adrenal gland
What are some of the non metazoic effects of lung cancer?
ACTH production ADH production PRH production encephalopathy cerebellar degenertion neuropathy myopathy eaton lambert syndrome
Describe small cell carcinoma
most aggressive form
metastasises early and wide
good initial treatment response but most relapse
What types of non-small cell carcinoma?
sqaumous
adenocarcinoma
large cell
Describe squamous cell carcinoma
major bronchi
slow growth - surgery
may undergo cavitation
may lead to retention pneumonia or collapse
Describe adenocarcinoma of the lung
common in females
mainly in periphery
may produce mucin
Describe large cell carcinoma
diagnosis of exclusion
centrally arising
What is mesothelioma?
primary pleural tumour
almost always due to asbestos exposure
Describe dermatophytes
fungi that cause common infections of skin, nails and hair
do not colonise live tissues - only keratinised areas
healthy and immunocompromised equally infected
ringworm / tinea
What is the treatment of dermatophytes?
over the counter products
topical administration apart from severe, nail infections
terbinafine
What are systemic fungal infections?
fungal meningitis - cryptococcus neoformans aspergiollosis of lungs aspergillus fumigatus pneumocystic pneumonia pneumocystis jirovec
Describe cryptococcus neoformans
inhaled opportunistic pathogen encapsulated yeast contracted from environment lungs / meningitis 2 weeks of amphotericin B for meningitis fluconazole or flucysosine (non CNS)
Describe aspergillus fumigatus
allergic bronchopulmonary aspergillosis
invasive pulmonary aspergillosis
aspergilloma
Describe pneumocystis jiroveci
common environmental fungus
pneumonia - fever, cough, SOB
treatment and prophylaxis - trimethoprim-sulfamethoxazole
Describe imidazole, triazole and thiazole antifungals
largest class of anti fungal agents many applications multiple types of drugs
What is the mechanism of action of azole drugs?
inhibitors of 14-methylsterol alpha demethylase which produces ergosterol
essential component of fungal plasma membrane
does not occur in plant or animal cells
Describe the action of amphotericin B
exploits ergosterol/cholesterol difference not an enzyme inhibits exploits the presence of ergosterol forms pore in fungal membranes leakage of intracellular cations cell death
How is a life threatening acute exacerbation of asthma treated?
high flow oxygen nebulised bronchodilators (500mg salbutamol, 500mcg ipatropium bromide) oral prednisalone 40mg oral doxycycline 200mg IV magnesium 2g Discussion with ITU consider IV aminophylline infusion
What is the mechanism of action of corticosteroids?
bind to activated glucocorticoid receptors to suppress multiple pro-inflammatory genes that are activated in asthmatic airways by reversing histone actetylation
What are the indications of inhaled corticosteroids
asthma
COPD with recurrent exacerbations
What are the side effects of corticosteroids?
diabetes, osteoporosis, hypertension, muscle wasting, peptic ulcer, cataracts, cushings syndrome, adrenal suppression, acute pancreatitis, hyperlipidaemia, increased appetite, salt and water retention , immune suppresion
What is the mechanism of action of Beta 2 agonists?
higher specificity for pulmonary beta 2 receptors vs cardia B1 receptros
stimulate adenyl cyclase to increase intracellular cAMP - relaxation of bronchial smooth muscle
What are the indications for b2 agonists?
asthma
COPD
What are the side effects of B2 agonists?
tremor hypokalaemia hypergylcaemia hypomagnasmaemia flushing tachycardia arrhythmias headache muscle cramps
What is the mechanism of action of anti-muscarinics?
inhibition of cholinergic M1 and M3 receptor in lung - reduction in cGMP and inhibition of parasympathetic mediated broncoconstriction
What are the side effects of anti-muscarinics?
blurred vision, dry mouth, urinary retention, nausea, constpiation,
nebulised ipatropium may precipitate acute angle closure glaucoma
What is the mechanism of action of methylxanthines?
non-selective inhibition of phosphodiesterase - increased cellular cAMP, bronchial smooth muscle relaxation
improved mucocilliary clearance and anti-inflammatory effect
What are the indications for methylxanthines?
Adjunct to inhaled therapies in asthma / IV infusion in severe exacerbations
What are the side effects of methylxanthines?
GI upset, tachycardia, headache , insomnia, hypokalaemia
Describe leyukotrine receptro antagonists
bind with high affinity to cysteinyl leukotriene receptor, inhibiting the action of LTDA in smooth muscle cells of the airway and airway macrophages - reduced oedema and smooth muscle contraction
Describe omalizumab
monoclonal anti-Ig£ antibody
severe persistent allergic asthma
subcut injection every 4 weeks
Describe mepolizumab
anti-IL5 monoclonal antibody reduces circulating eosinophils severe refractory eosinophilic asthma sub cut injection every 4 weeks headaches commonly reported
Give examples of other drugs used in COPD
roflumilast -reduced inflammation
azithromyicin - anti-inflammatory effects
carbocysteine - reduced sputum viscosity
