Respiratory Flashcards
Signs of pneumothorax on examination
From the end of the bed the patient may be tachypnoeic.
Diminished breath sounds on side of PTX on auscultation, and hyper-resonant on percussion.
Reduced chest expansion may be evident on side of PTX.
What would a CXR of a tension PTX show?
But why would this not usually be seen?
the heart and mediastinum will be being pushed to the opposite side due to the high pressure on the side of the PTX
should not be seen because the aim is to make a diagnosis based on symptoms in order to not delay treatment
what happens in a tension PTX?
A “one-way valve” establishes itself which allows air into the pleural cavity on inspiration, but closes on expiration to cause an increase in pressure
This will continue until the patient’s venous return to the heart is compressed and obstructed causing cardiac output failure and the patient will arrest
how to make a clinical diagnosis of tension PTX
Severe tachypnoea, may be cyanotic
Tachycardic, hypotensive
Raised JVP
Tracheal deviation
Absent breath sounds, hyper-resonant and hyperexpanded chest unilaterally
Immediate management of tension PTX
Large bore (14 or 16 gauge) needle decompression – 2nd intercostal space, mid-clavicular line.
Followed by tube thoracostomy
Primary vs. Secondary PTX
Primary occurs in otherwise healthy lung tissue
Secondary occurs due to underlying lung disease
What is asthma?
a disease involving bronchoconstriction and inflammation
causes variable and reversible increases in airway resistance
What FEV1:FVC ratio suggests increased airway resistance?
a ratio of less than 70-80%
Timing of symptoms of asthma
Symptoms tend to worsen at night or early in the morning, and symptoms tend to vary over time
Asthma symptoms
wheeze, shortness of breath, chest tightness and cough
Non-specific triggers for asthma
Viral infections Cigarette smoke Pollution Cold weather Emotion Exercise (sometimes)
Specific triggers for asthma
Pets
Pollen
Other allergens
Occupational pollutants
Important HPC/PMH points for asthma
Known precipitants
Diurnal variation in symptoms
Acid reflux symptoms (known association).
History of atopy.
History of these episodes (and establish whether they required hospital/ITU)
Relevant DHx for asthma
NSAIDs (particularly aspirin) and beta-blockers, as these can cause asthma
Relevant FH and SH for asthma
FH of atopy
Very important to ask about occupation (as there can be occupational pollutants such as flour or chemicals).
Days off work/school.
Smoking.
Diagnosis of asthma
Requires a structured clinical assessment to see if:
Episodes are recurrent
Symptoms are variable
PMH/FH of atopy.
Recorded observation of expiratory wheeze.
Variable peak expiratory flow or FEV1
Absence of symptoms of an alternative diagnosis.
If these give a high probability of asthma – diagnose as suspected asthma and initiate treatment
When is a diagnosis of asthma confirmed?
When there is objective improvement after initiating treatment.
if response to treatment is poor, refer for spirometry to test for airway obstruction with bronchodilator reversibility (FEV1/FVC <70% with bronchodilator reversibility is diagnostic)
Diagnosis of asthma in children
Children <5 with suspected asthma should have symptoms treated based on observations and clinical judgement and be reviewed regularly until they are old enough to do objective testing
Extrinsic Asthma:
Type I hypersensitivity reaction
Most frequently occurs in atopic individuals who show positive skin prick tests to common allergens, implying a definite extrinsic cause.
Tends to be early-onset
Intrinsic Asthma
Non-immune mechanisms
Occurs in middle-aged individuals, when no causative agent can be identified
Generally more severe, and associated with quicker deterioration of lung function.
Tends to be late-onset
Pathophysiology of asthma
- Spasmogens will act rapidly to cause smooth muscle contraction of the airways, leading to bronchospasm.
- Chemotaxins are released to stimulate eosinophils and mononuclear cells to go to the airways, causing an inflammatory response a few hours later.
Persistant airway obstruction in asthma
can become indistinguishable from COPD
more common in intrinsic asthma
bronchoconstriction due to increased responsiveness of bronchial smooth muscle, and hyper-secretion of mucous that plugs the airways
Sputum will contain Charcot-Leyden crystals (from eosinophil granules) and Curschman spirals (mucous plugs from small airways).
Can eventually lead to pulmonary hypertension
what is the basis of asthma treatment?
The use of bronchodilators reverses the bronchospasm and provides rapid relief – “relievers”.
There are also treatments to prevent more attacks – “preventers” – which are usually anti-inflammatory steroids
=> aim is to have no daytime symptoms, no night time waking, no need for rescue medication and no limitations on activity.
beta2-adrenoceptor agonists in asthma
typically the first-choice drug for relief.
Can be short-acting/long-acting (SABA / LABA)
Acts on beta2-adrenoceptors on smooth muscle, which causes relaxation and in turn an increase in FEV1.
given by inhalation; localising the action and providing a rapid effect.
Prolonged use may lead to receptor down-regulation – the beta2-adrenoceptors become less responsive
Long-acting beta agonists
given for long term prevention and control (e.g. overnight), as it stays bound to the receptors for a lot longer than salbutamol (SABA)
corticosteroids in asthma
Preventative, they do not reverse an attack.
Takes 2-3 days to have an effect.
Anti-inflammatory by activation of intracellular receptors, leading to altered gene transcription (decrease cytokine production) and production of lipocortin/annexin A1.
It is thought that lipocortin/annexin A1’s action is to inhibit phospholipase A2, and therefore inhibiting the synthesis of PGs and LTs by preventing the arachidonic acid pathways from occurring.
Leukotriene receptor antagonists (LTRAs) in asthma
e.g. Montelukast
Increased role as add on therapy.
Have both preventative and bronchodilator uses.
Antagonises the actions of LTs by blocking their receptors
Also useful against symptoms of hayfever and eczema
Xanthines in asthma
e.g. theophylline, aminophylline.
These are also bronchodilators, but not as good as beta2-adrenoceptor agonists (therefore only 2nd line use).
Oral (or IV aminophylline in emergency)
Adenosine receptor antagonist.
Phosphodiesterase inhibitors, preventing the breakdown of cAMP.
Pharmacological treatment of SUSPECTED asthma
All patients with suspected asthma should receive a SABA.
Pharmacological treatment of CONFIRMED asthma
SABA + ICS => Add LABA (or LTRA/xanthine if this fails). => Increase dose of ICS => Add oral steroid
if salbutamol inhaler is used more than 2 times a week, this indicates that their current control is inadequate, and the care needs to move up a step
Moderate Acute Asthma
Increasing symptoms
PEF 50-75%
No features of acute severe asthma
Acute Severe Asthma
Requires any one of: • PEF 33-50% predicted • RR >25/min • HR >110 • Inability to complete sentences in one breath
Life-threatening Asthma
Any one of: • PEF <33% predicted • SpO2 <92% • PO2 <8kPa • Normal PaCO2 (4.6-6) • Silent chest • Cyanosis • Poor respiratory effort • Arrhythmia • Exhaustion • Altered consciousness • Hypotension
Emergency management of asthma
If a patient has ANY life-threatening feature, an arterial blood gas is the only immediate investigation required whilst treatment is initiated.
- O2 to maintain sats at 94-98% (88-92% in COPD, 92-94% in Covid)
- Salbutamol nebuliser (add ipratropium if required).
- Steroids (PO prednisolone or IV hydrocortisone)
- IV magnesium sulphate
- IV aminophylline (senior review)
- Referral to ITU for patients who are not improving.
What blood gas features are markers of a life-threatening asthma attack?
Normal PaCO2 (should normally be low due to hyperventilation).
Severe hypoxia <8 kPa
A low pH
What is COPD?
= Chronic Obstructive Pulmonary Disease.
Characterised by airflow obstruction, which is usually progressive and not fully reversible.
Obstruction does not change markedly over several months.
What causes COPD?
significant exposure to noxious particles/gases.
> 90% caused by damage to the lungs from smoking.
pathological changes in COPD
- Chronic inflammation – chronic response to irritants
* Structural change – repeated injury and repair
physiological changes in COPD
Mucous hypersecretion
Ciliary dysfunction
Airflow limitation, resulting in alveolar hyperinflation.
Impaired gas exchange
Pulmonary hypertension – due to remodelling of pulmonary arteries and veins.
Risk factors for COPD
SMOKING!!!!!!
Indoor air pollution
Occupational toxins
(Outdoor air pollution)
Genetic factors – alpha-1 antitrypsin deficiency.
Infections – measles, whooping cough.
Socio-economic factors – significant association with socio-economic deprivation.
Asthma and airway hyperreactivity
Clinical features of COPD
Chronic progressive dyspnoea
A chronic cough
Regular sputum production
Wheezing and chest tightness
These symptoms become exacerbated in acute infective episodes.
In severe cases, there may be fatigue, weight loss, anorexia, cough, syncope, depression/anxiety
Complications of COPD
- Acute exacerbations
- Polycythaemia
- Respiratory failure
- Cor pulmonale
- Pneumothorax
- Lung carcinoma
COPD - OE: observations
- Tachypnoea
- Possible cyanosis
- Flapping tremor (if CO2 retainer, >10 kPa)
- Cachexia
COPD - OE: inspection
- Hyperinflation
- Intercostal recession on inspiration
- Lip pursing on expiration
- Signs of respiratory distress.
- Raised JVP
- Peripheral oedema
COPD - OE: palpation
• Poor chest expansion
COPD - OE: percussion
- Hyper-resonant throughout
* Loss of cardiac/hepatic dullness.
COPD - OE: auscultation
- Widespread/polyphonic wheeze, or
- Decreased breath sounds
- Prolonged expiratory phase.
“Pink Puffer”
Patients remaining sensitive to CO2, thus keep a low CO2 and near-normal O2.
Tachypnoeic, tachycardic, using accessory muscles to increase ventilation.
Breathless but not cyanosed.
Very thin – large amounts of calories used to breathe.
Can progress to type 1 respiratory failure.
More emphysematous.
“Blue Bloater”
Patients are insensitive to CO2.
Severe chronic bronchitis/COPD.
Not particularly breathless but are cyanosed and oedematous (cor pulmonale).
Blood gas will show type 2 respiratory failure (low oxygen, retaining CO2.
Oxygen should be given with care to these patients.
What main investigations would you order for suspected COPD?
FBC
CXR
Spirometry
What additional investigations could be ordered in suspected COPD?
Serial peak flow, Alpha 1 antitrypsin, Transfer factor for carbon monoxide. Pulse oximetry, CT thorax ECG Echo
ABG – normal in mild disease, developing to type 1/2 respiratory failure.
Sputum culture – abnormal organisms suggest bronchiectasis.
COPD - FBC
Secondary polycythaemia
Any anaemia?
Secondary polycythaemia
= the overproduction of red blood cells
due to chronic hypoxaemia, which triggers increased production of EPO by the kidneys
causes your blood to thicken, which increases the risk of a stroke.
COPD - CXR
Hyperinflation (>6 anterior and >10 posterior ribs)
Flattened hemidiaphragm
Rule out malignancy/other diagnoses
Staging of COPD by spirometry
Stage 1 – FEV1 >80% predicted (clinical diagnosis); mild.
Stage 2 – FEV1 50-79% predicted; moderate.
Stage 3 – FEV1 30-49% predicted; severe.
Stage 4 – FEV1 <30% predicted; very severe.
Management of COPD
Patient education - how to recognise and manage exacerbation
Lifestyle advice - diet, exercise, STOP SMOKING
Pneumococcal vaccine
Medical management
Medical management of COPD
Short-acting bronchodilators (SABA or SAMA)
If no features of asthma/steroid responsiveness:
- Add a long-acting beta-agonist (LABA) and muscarinic agonist (LAMA)
- Add inhaled corticosteroids if still symptomatic
- Remove ICS after 3 months if no improvement.
If features of asthma/steroid-responsiveness are present – LABA + ICS.
- LABA + LAMA + ICS if ongoing symptoms.
What are features of asthma/steroid-responsiveness in COPD?
Previous diagnosis of asthma/atopy, blood eosinophilia, substantial variation in FEV1 over time or diurnally.
Specialist treatments for COPD
Pulmonary rehabilitation – consider if someone is functionally disabled by COPD.
Oral aminophylline/theophylline – if still symptomatic after trial of triple therapy.
Mucolytics – e.g. carbocysteine
Roflumilast – PDE4 inhibitor
Nutritional supplements – consider for low BMI
Long-term oxygen therapy
Surgery
Acute exacerbation of COPD
Exacerbations are frequently caused by bacterial/viral infections, or exposure to pollutants.
Dyspnoea and wheeze will become worse, with increased production of purulent sputum.
Patient should have rescue medications.
Hospital admission in severe breathlessness, rapid symptom onset, acute confusion, cyanosis, low oxygen sats, or worsening peripheral oedema.
Steps for smoking cessation
- ASK about smoking at every opportunity.
- ADVISE all smokers to stop smoking.
- Offer ASSISTANCE to all smokers to stop.
- ARRANGE smoking cessation follow-up.
What are some useful things to do when helping someone to stop smoking.
- Set a date to stop completely
- Specialised stop-smoking clinics
- Review previous quit attempts (what helped/hindered)
- Plan for problems and how to manage them
- Plan for how to handle alcohol drinking situations
- Try smoking cessation treatments
What are some treatments to help smoking cessation?
Nicotine replacement therapy
Bupropion
Epidemiology of Lung Cancer
Lung cancer is the third most common cancer in the UK.
Incidence increases with age
Lung cancer is the most common cause of cancer deaths in the UK (accountable for ~1 in 5)
79% of lung cancers are preventable.
Risk factors for developing lung cancer
Smoking
Second-hand/environmental smoking
Old age
Air pollution
Radon
Occupational hazards (e.g. asbestos, silica)
Family History of lung cancer in a close relative.
Lung cancer - Clinical Features
- Persistent cough – non-specific sign.
- Haemoptysis – less common but more specific.
- Dyspnoea
- Dysphagia
- Hoarseness
- Chest pain – pleural/chest wall involvement.
- Fatigue, Weight loss, Appetite loss, Fever
Lung cancer - On Examination
- Clubbing
- Cachexia
- Signs of anaemia
- Chest signs of collapse/consolidation/effusion
- Signs of metastases.
- Hypertrophic pulmonary osteoarthropathy – a paraneoplastic syndrome
What is the rough split between incidence of small cell and non-small cell lung cancers
Small-cell - 15%
Non-small cell - 85%
Small cell (“oat cell”) carcinomas
Rarer but highly malignant, grow very quickly and metastasise early.
Rare in non-smokers.
Usually centrally located.
Originate mostly from bronchial epithelium, but differentiate into neuroendocrine cells (e.g. secreting ADH, ACTH, etc.) and causing paraneoplastic syndrome.
Squamous cell carcinoma
non-small cell
Arise from squamous metaplasia of the normally pseudostratified ciliated columnar epithelium
Occur mainly in response to cigarette smoke exposure.
Usually central, close to the carina.
May secrete PTH, causing hypercalcaemia (can also be due to secondary bone metastases).
Can often be diagnosed with sputum cytology.
Tends to cause cavitating lesions.
Slow growing, may be resectable.
Adenocarcinoma
non-small cell
Equal gender incidence, and less related to smoking.
Characteristically originate in peripheral locations (potentially areas of previous lung scarring).
Associated with asbestos exposure.
Large cell carcinoma
non-small cell
Features showing small cell/adenocarcinomatous origins may be seen, but they are not differentiated enough to eb classified.
Poor prognosis, often widely disseminated at diagnosis.
Bronchoalveolar carcinoma
a special type of adenocarcinoma,
Rare but associated with better prognosis.
Metastatic lung tumours
the lungs are a common site of metastasis of many cancers.
secondary lung tumours will be made up of cells of the primary tumour.
Local complications of lung tumours
SVC compression
Recurrent laryngeal nerve palsy
Horner syndrome
Distant metastasis of lung tumours
Most common sites – brain, bone, liver, adrenal glands.
Symptoms will be associated to the specific organ affected
Lung tumours - SVC compression
Raised JVP, raised arm BP/swelling, facial swelling.
Common presenting feature of lung cancer.
Often due to local nodes rather than the tumour itself
Lung tumours - Recurrent laryngeal nerve palsy
voice hoarseness and left vocal cord paresis.
If present, indicates tumour inoperability.
Lung tumours - Horner syndrome
Miosis, ptosis, anhidrosis
Destructive lesions of the thoracic inlet, often involving the brachial plexus.
Due to Pancoast tumour
CXR in suspected lung cancer
For anybody with suspected lung cancer - first investigation is a CXR.
Also, ANY patient with haemoptysis should have a CXR
Symptomatic tumours are almost always visible.
A normal CXR in a symptomatic patient should warrant further investigation for central tumours
Blood tests in suspected lung cancer
FBC - anaemia/secondary polycythaemia
U&E - hypercalcaemia, hyponatraemia
LFTs - liver mets?
What are the steps in suspected lung cancer?
CXR
Bloods
Any patient presenting with any suspicion of lung cancer requires a 2-week wait referral to a lung cancer clinic for further investigation
Specialist referral for:
- sputum/pleural cytology
- contrast-enhanced CT staging
- bronchoscopy
- pulmonary function tests
- PET scan if suspected metastasis.
How much fluid is normally within the pleural cavity?
~15 mL of serous pleural fluid
What is pleural effusion?
the build-up of excess fluid between the layers of the pleura outside the lungs
How does pleural effusion differ from pulmonary oedema?
the location of the fluid
Pleural effusion - fluid in pleural space
Pulmonary oedema - fluid in alveolar spaces and lung tissue
Haemothorax
= accumulation of blood, due to trauma
Empyema/pyothorax
= accumulation of pus, due to infection
Chylothorax
= accumulation of lymph, due to thoracic duct leakage
Fluid effusion
= fluid accumulation, transudative or exudative
Transudate
Occur due to increased hydrostatic pressure/decreased oncotic pressure
Causes – cardiac failure, liver failure, renal failure, peritoneal dialysis.
Rarer causes – hypothyroidism, ovarian tumours.
What is the protein concentration of transudate?
Protein concentration <30 g/L
Exudate
Occur due to increased capillary permeability
- Infections – bacterial pneumonia, TB
- Neoplasm – lung primary/secondary, mesothelioma.
- Pulmonary Embolism
- Autoimmune disease – RA/SLE
- Abdominal disease
What is the protein concentration of transudate?
Protein concentration >30 g/L
If protein level of pleural fluid is 25-30 g/L, what criteria are needed to suggest it is an exudate (not transudate)?
one positive element of Light’s criteria will suggest an exudate:
- Pleural fluid protein/serum protein >0.5.
- Pleural fluid LDH/serum LDH >0.6.
- Pleural fluid LDH more than two-thirds the upper limit of normal serum LDH.
Symptoms of pleural effusion
A small amount of fluid is completely asymptomatic
As the volume of fluid increases, the patient will experience: • Shortness of breath • Cough • Pleuritic chest pain • Reduced exercise tolerance
Pleural effusion - percussion
dull due to underlying fluid
Pleural effusion - auscultation
quieter breath sounds and vocal fremitus
What is the first-line investigation on suspicion of a pleural effusion?
CXR
What is the issue in using a CXR in ?pleural effusion
PA and AP erect X-ray films are insensitive to small amounts of fluid – as much as 250-600 mL of fluid is required before it becomes evident.
CXR features indicating pleural effusion
- blunting of the costophrenic angle
- blunting of the cardiophrenic angle
- fluid within the horizontal or oblique fissures
- eventually, a meniscus will be seen (note: if a hydropneumothorax is present, no such meniscus will be visible)
- with large volume effusions, mediastinal shift occurs away from the effusion
Pleural effusion - ultrasound
allows the detection of small amounts of pleural locular fluid, with positive identification of amounts as small as 3-5 mL.
It is it is effective in guiding thoracocentesis (even in small fluid collections) and can be used to assess pleural fluid volume.
Treatment of pleural effusion
The treatment of pleural effusions is usually targeted to the underlying condition.
Ultrasound-guided aspiration is reliable and fast and enables loculated effusions to be drained. Symptomatic patients with large effusions may be treated by therapeutic aspiration/pleural tap.
Fluid can be sent to microbiology and also be assessed for clinical chemistry (protein, LDH, glucose) and cytology. It can also be run through a blood gas machine to assess pH.
Community-acquired pneumonia definition
Clinical lower respiratory tract infection AND
New pneumonic changes on CXR AND
Onset of symptoms in the community OR within 48 hours of hospital admission.
CAP is more common in…
- Males
- Winter/early spring
• The elderly – peak age 50-70 years; most severe in age >65.
- Alcoholics
- Smokers
- People with established chronic disease
CAP presentation
The patient presents with symptoms of LRTI – cough, sputum, breathlessness, pleuritic chest pain, occasionally haemoptysis
These symptoms are similar to bronchitis, and for a diagnosis of CAP you need evidence of lung parenchymal involvement (confirmation with CXR).
CAP presentation in the elderly
Elderly populations may present with very few symptoms, but be very unwell and usually acutely confused
Causes of CAP
Conventional bacteria (60-80%) => S. pneumoniae, H. influenzae
‘Atypical’ bacteria (10-20%)
Viruses (10-20%)
What are the “atypical” bacteria causing CAP?
Mycoplasma pneumoniae,
Chlamydia pneumoniae
Legionella pneumophila
CAP - on examination
Inspection:
• Tachypnoea
Palpation:
• Decreased chest expansion on the affected side.
Percussion:
• Dullness over the affected area
Auscultation:
• Coarse crackles and pleural rub over the affected area
• Bronchial breathing
• Increased vocal resonance – “111” / “99” can be heard better due to consolidation.
ALSO there can be upper abdominal tenderness in lower lobe pneumonia.
Investigations for CAP
- Confirm diagnosis – CXR
- Assess severity of disease – CURB65
• Identify complications
=> Often linked to respiratory failure (T1RF/T2RF)
=> Can lead to multi-organ failure, septic shock and death.
=> Will the patient need supplementary oxygen therapy to maintain PO2 >94 (or >88 COPD)?
=> Bloods – LFTs, FBC, CRP, Arterial Blood Gas.
Microbiological investigations for CAP
• Sputum analysis and culture
• Immunofluorescence on sputum/nasopharyngeal samples
=> Viruses (influenza), mycoplasma, legionella
• Blood cultures
• Urinary pneumococcal and legionella antigen
=> For any patient with moderate/severe CAP!
CURB65 criteria
Confusion – mini-mental test score of 8 or less (new)
Urea >7 mmol/L (new)
Respiratory Rate >30 breaths per minute
Blood Pressure – systolic BP <90 mmHg or diastolic BP <60 mmHg
65 or more years old
Low-severity CAP
CURB score 0 or 1
Management of Low-severity CAP
PO Amoxicillin, managed as outpatients.
PO doxycycline if penicillin allergy.
Moderate-severity CAP
CURB score 2
Management of Moderate-severity CAP
Higher mortality – ~5-10%
PO amoxicillin + clarithromycin, usually admitting the patient
Severe CAP
CURB score >2
Management of Severe CAP
Can be >20% mortality if established failure in another organ system.
Requires admission to at least Level 01 unit or even HDU/ICU.
IV co-amoxiclav + clarithromycin.
Penicillin allergy/MRSA suspicion – vancomycin and levofloxacin.
Treatment for at least 10 days.
Pneumonia follow-up
Patients should always have a follow-up CXR at 6 weeks to ensure resolution of consolidation and assess for persistent abnormalities of the lung parenchyma
CAP non-resolution
?endobronchial obstruction as cause of pneumonia (e.g. lung cancer)
Definition of hospital-acquired pneumonia
Clinical lower respiratory tract infection AND
New pneumonic changes on CXR AND
onset of symptoms > 48 hours after admission OR admission in the last 7 days
when is there increased risk of HAP?
prolonged hospital stays, poor mobility, age >70 years and severe underlying disease.
What are the causes of HAP?
Tends to be more gram negative pathogens
Enteric gram-negative bacilli – ~60% HAP cases
Also:
Strep. pneumoniae
H. influenzae
Staph. aureus
Management of HAP
Assess MRSA risk factors
Assess HAP severity
Mild HAP – oral doxycycline.
Severe HAP – IV Tazocin.
Aspiration pneumonia
Aspiration of gastric contents leading to chemical inflammation and infection.
When should you suspect aspiration pneumonia?
Does not always show on CXR!!
Suspect it for example in someone who has a low GCS and evidence of vomiting (so at risk of aspirating).
What should you do in suspected aspiration pneumonia?
If suspected can add metronidazole for HAP or CAP – this is to cover anaerobic bacteria.
Complications of pneumonia
Sepsis
Septic shock
Lung abscess
Empyema
Complications of pneumonia - empyema
= pus-filled collection in the pleural space.
Seen especially in streptococcus pneumonia
Complications of pneumonia - lung abscess
= pus-filled collection in the lung parenchyma
Seen especially in Staph. aureus pneumonia.
When should you suspect lung abscess/empyema?
if there is a persistent swinging pyrexia and rising CRP despite treatment.
characteristics of Mycobacterium tuberculosis
an aerobic bacillus:
Non-motile
Cell envelope which resists gram staining.
Known as “acid fast bacilli” or AFBs
Very slow growing.
In which groups in the UK is TB particularly common?
immigrant ethnic groups,
the socially disadvantaged,
HIV +,
Londoners
How is TB transmitted?
The person with pulmonary TB can cough and expel infectious droplets. Infectious particles can remain suspended in the air for several hours and inhaled aerosolised droplets lodge in the alveoli.
What are factors that determine the probability of TB transmission?
Susceptibility of exposed person - e.g. HIV+
Infectiousness - number of bacilli expelled into the air
Environment - e.g. enclosed spaces
Exposure - proximity, frequency, duration
Primary TB infection
occurs when a non-immune host (never met TB before) is exposed to M. tuberculosis
The process of primary TB infection
- TB containing droplets reach the alveoli and are taken up by macrophages
- If macrophages fail to kill TB, primary infection occurs.
=> TB bacilli then slowly multiply inside the macrophages.
=> macrophages can carry TB to local lymph nodes or further around the body.
=> granulomatous lesions beginning to develop in the lungs. - At this point a complex interplay between host and bacteria occurs to determine whether active or latent disease occurs.
=> Factors such as number of TB bacteria inhaled and whether the host is immunocompetent.
When do the caseating granulomas of TB develop?
The tissue reaction in the lungs and lymph nodes changes to form caveating granulomas ~1-2 weeks after infection.
Latent TB infection
LTB occurs when the host defences are able to contain the TB infection.
Over around 2-6 weeks the adaptive immune response kicks in and and a granuloma forms to contain the TB infection.
The TB within the granuloma is DORMANT, therefore, latent TB can always be reactivated
but people with LTB do not have active disease and are not infectious
Post-primary TB infection
occurs when latent TB becomes reactivated.
This may stay local or spread to more distant sites, causing extra-pulmonary TB.
Cavities and progressive lung destruction lead to cough and systemic symptoms (patient is infectious again)
Which people are at a higher risk of TB reactivation?
Untreated HIV+
Immunosuppressed for other reasons – e.g. long-term steroids, organ transplant.
Comorbidities – e.g. diabetes and CKD
Aging
% risk of LTB reactivation
LTB + no risk factors – 10% risk of reactivation over lifetime
LTB + untreated HIV – 7-10% risk of reactivation per year.
Investigating TB
- Culture:
=> Pulmonary TB – several sputum samples (at least one in early morning) to look for acid fast bacilli down the microscope and then culture.
=> PCR if rapid diagnostic results required or suspected MDR-TB
=> Culture is gold-standard test but takes 6 months.
=> Non-Pulmonary TB – a sample from the suspected site to culture
- Histology – classically will find caseating granuloma
- Imaging
=> CXR – different findings for primary, latent and post-primary, but also significant overlap!
CXR in Primary TB
Caseating granulomas/Ghon focus
=> These represent healing of a primary TB infection.
Lobar or patchy consolidation
Effusions and regional lymphadenopathy
Ghon focus and complex
Calcified caseating granulomas
if seen with regional lymphadenopathy then called Ghon complex
miliary TB
where the TB spreads rapidly though the body
looks like ‘Millet seeds’ on CXR
more common if immunosuppressed
CXR in Post-primary TB
characterised by:
- necrosis and cavitation formation
- Progressive lung destruction
Cavities now tend to be apical (more oxygen).
CXR in latent TB
Should be normal!
Very occasionally a few nodules.
There should be no signs of active TB disease.
When would you investigate for Latent TB?
close contacts of active TB patient (contact tracing);
someone who has come from a high incidence TB country
How do you investigate for latent TB?
Mantoux test/tuberculin skin test
=> can get false positives if prior BCG vaccine or false negatives with HIV infection
Interferon-gamma release assay (IGRA) test
=> no false negatives with HIV or cross reaction with BCG
Positive results should lead to assessment for active TB (as these tests cannot differentiate between active/latent disease). If no evidence of active TB, treat as latent TB.
Presentation of pulmonary TB
Cough
Haemoptysis
Fever
Systemic symptoms – night sweats, weight loss, fatigue.
Presentation of extra-pulmonary TB
Common sites include the larynx, pleura, brain, kidneys and bone.
Presentation varies, as it depends on the site
Management of active TB
Therapy consists of 6 months of treatment, which can be divided into:
- “bactericidal” phase in which the majority of organisms are killed = four drugs for two months
- “sterilising” phase in which persisting organisms are eliminated = two drugs for four months.
Standard therapy in the UK (BTS 1998) is:
- Rifampicin, isoniazid, pyrazinamide and ethambutol given for a two-month period.
- Followed by Rifampicin and isoniazid for four months.
What is given as a supplement with isoniazid?
given with pyridoxine supplements to prevent peripheral neuropathy.
Why is combination therapy essential in treating active TB?
Mycobacteria mutate to develop single drug resistance.
in a bacillary population of sufficient size, single drug therapy will always select resistant organisms.
Management of latent TB
Isoniazid for 6 months
OR
Rifampicin and Isoniazid for 3 months
TB resistance / MDR TB
The most common drug resistance in the UK is isolated Isoniazid resistance, with rifampicin being the marker for multi-drug resistant TB
Who is at risk of MDR TB?
Individuals previously treated for TB
Known contact with a case of drug resistant TB
Acquisition of infection in a country or group with high prevalence of drug resistance (e.g. Tanzania).
Patients who fail to make a satisfactory response to adequate conventional treatment
Co-existing HIV infection
What is bronchiectasis?
a disease involving inflammation which causes permanent dilation of the subsegmental airways (bronchi and bronchioles)
leads to a build-up of excess mucous.
How is there a two-fold effect of deadspace created in bronchiectasis?
- The damage will significantly reduce the surface area to volume ratio.
- Airways become filled with secretion, so less oxygen can reach the alveoli.
What are the types of bronchiectasis?
Cylindrical (most common)
Varicose
Cystic (most severe, least common)
Cylindrical bronchiectasis
airways are widened, but structure tends to be the same
Varicose bronchiectasis
architecture is also damaged as well as widened ariways
Cystic bronchiectasis
development of out-pouches/bulges, which can impinge on healthy airways
Vicious cycle hypothesis of bronchiectasis
an initial insult leads to the start of the chain reaction of:
Respiratory tract infection & Bronchial Inflammation & Respiratory tract damage
What can be the initial insult of bronchiectasis?
Congenital (e.g. CF)
Infective (viruses, bacteria, fungi)
Obstruction (e.g. COPD, tumours, foreign bodies, irritants)
Other (e.g. Idiopathic)
Long-term consequences of bronchiectasis
Recurrent pneumonia
Pleural effusions – accumulated inflammatory transudate.
Secondary pneumothorax
Massive haemoptysis – larger vessel eroded by chronic disease
Right heart failure – increased pulmonary resistance.
Rarely – cerebral abscess and amyloidosis
Typical Presentation of bronchiectasis
Shortness of Breath
Fatigue
Copious amounts (“cupfuls”) of sputum, sometimes with blood. => Productive cough
Previous infection/history of lung disease – e.g. pneumonia
Atypical Presentation of bronchiectasis
Idiopathic bronchiectasis – no history of lung disease.
Dry bronchiectasis – no excessive sputum production
COPD-bronchiectasis overlap
What is the difference between the early stages of COPD and bronchiectasis?
COPD is a functional/physiological diagnosis – due to poor reversible airflow obstruction.
Bronchiectasis is a structural diagnosis – presence of airway dilatation on CT
=> initially restrictive due to widening of airways,
=> then obstructive as airways fill up with fluid/mucous,
=> eventually mixed deficit towards the advanced stages of disease
Bronchiectasis - on examination
Acute signs:
- Rronchi (loud expiratory wheezing)
- Mid-inspiratory squeaks
- Coarse crackles
Chronic signs – maybe acute signs, but also potentially:
- Generalised wheezing
- Clubbing
- RHF (raised JVP, oedema)
Bronchiectasis - investigations
Routine bloods – FBC, U&E, CRP, coagulation.
Sputum Microbiology – identify causative or propagating organism
=> Treat with broad spectrum initially, target once known.
=> If negative, consider fungal infection.
CXR
=> ?pneumonia, ?effusion,
=> might see some bronchial thickening,
Pulmonary function tests – will show obstructive picture (FEV1/FVC <0.7)
What would a high resolution CT scan of a patient with bronchiectasis show?
Signet ring pattern
Restrictive Lung Disease
= physical reduction in potential maximum lung volume
Can be:
- A problem of compliance – e.g. fibrosis
- An increase in dead space – e.g. effusion, pus
Obstructive lung disease
= increased effort to reach near-normal lung volume, due to narrowing of airways
Can be:
- obstruction of large airways – asthma, COPD, bronchitis
- obstruction of small airways – bronchiolitis, bronchiectasis
What is FEV1?
What is considered normal?
= the volume exhaled in the first second after deep inspiration and forced expiration
Normal is >80%
What is FVC?
What is considered normal?
= the total volume of air that can be forcibly exhaled in one breath from maximal inhalation
Normal is >80%
What is FEV1/FVC?
What is considered normal?
a ratio used to identify restrictive/obstructive deficit.
Normal is >70%
Spirometry in obstructive lung disease
FEV1 <80%
FVC >80%
FEV1/FVC <0.7
Spirometry in restrictive lung disease
FEV1 <80%
FVC <80%
FEV1/FVC >0.7 (i.e. normal)
What causes non-lung related restrictive deficit?
Pregnancy, obesity, kyphoscoliosis
What is pulmonary fibrosis?
a condition in which there is diffuse scarring of the lung parenchyma
Focal pulmonary fibrosis
The occupational Lung Diseases (OLD)
=> affects lymphoid tissue
Interstitial pulmonary fibrosis
Extrinsic Allergic alveolitis
=> affects parenchyma
Replacement pulmonary fibrosis
RA, TB, connective tissue disorders
=> direct damage due to disease
Apical pulmonary fibrosis
A TEA SHOP
Allergic Bronchopulmonary Aspergillosis Tuberculosis Extrinsic allergic alveolitis Ankylosing Spondylosis Sarcoid Histiocytosis Occupational (berylliosis, silicosis) Pneumoconiosis
Basal pulmonary fibrosis
DR CIA
Drugs Rheumatoid Arthritis Connective Tissue Disease Idiopathic Pulmonary fibrosis Asbestosis
Which drugs can cause pulmonary fibrosis?
amiodarone, bleomycin, busulfan, methotrexate, vincristine, nitrofurantoin
Which occupational lung diseases cause direct fibrosis?
Berylliosis – beryllium inhalation
Silicosis – silica/silicon inhalation
Asbestosis – asbestos inhalation
Which occupational lung diseases cause extrinsic allergic alveolitis?
Pigeon Fancier’s Lung – Bird dander/droppings
Farmer’s Lung – hay/crop mould
Malt worker’s lung – hop moulds
Hot tub lung – M. avium from hot tub mist.
Saxophonist’s lung – mixed fungi from uncleaned instruments
Pulmonary fibrosis - investigations
Bloods:
• ABG
• CRP
• Special tests
Imaging:
• CXR – reduced lung volume
• CT – classic signs of fibrosis: honeycombing.
Spirometry – restrictive deficit.
Lung biopsy – to assess for any fibrotic change ONLY if the CT scan and other tests are equivocal and diagnosis is uncertain.
what does pulmonary fibrosis look like on a high resolution CT?
Honeycombing
Prognosis of pulmonary fibrosis
Condition is progressive and life-limiting - prognosis is poor if untreated.
Treatment depends on the cause, and is often very limited.
Lung transplants can be done, but there is still risk of developing fibrosis in the new lung.
What are the three main buffering systems for H+ in the body?
- Intra- and extracellular buffers
- Ventilation
- Renal regulation of H+ and HCO3-
How does the body deal with an excess of H+?
buffers can combine with H+ to reduce levels
ventilation can increase to excrete CO2
Excreting H+ as free hydrogen ions or in phosphate/ammonia buffers
What pH is acadaemia and what pH is alkalaemia?
<7.35 is acidaemic
>7.45 is alkalaemic
Steps to interpreting an ABG
- How is the patient?
- Assess oxygenation
- Determine the pH
- Determine the respiratory component
- Determine the metabolic component
- Is there any evidence of compensation?
- Base excess
What should oxygenation on an ABG be?
PaO2 should be >10kPa on air, or
PaO2 should be ~10kPa less than the % inspired concentration.
What would respiratory acidosis look like on an ABG?
acidaemic
PaCO2 >6
What would respiratory alkalosis look like on an ABG?
alkalaemic
HCO3- >26
What does base excess look like on an ABG?
Negative in metabolic acidosis
Positive in metabolic alkalosis
What is base excess?
the theoretical amount of acid needed to bring a patient’s fully oxygenated blood to normal pH at room temperature
Respiratory Acidosis
Decrease in gaseous exchange leading to retention of CO₂
High PCO₂ leads to renal retention of bicarbonate to buffer excess H⁺
Compensation by the kidneys results in an increase in secretion of H⁺ over 3-5 days leading to increase in plasma bicarbonate level
Causes of respiratory acidosis
Drugs e.g. morphine and sedatives
Stroke
Infection
Asthma
COPD
Pneumoconiosis
Bronchitis
Acute respiratory distress syndrome (ARDS)
Poliomyelitis
Kyphoscoliosis
Myasthenia gravis
Muscular dystrophies
Obesity
Hypertension
Respiratory Alkalosis
Alveolar hyperventilation leads to excess exhalation of CO₂, resulting in low PCO₂
Compensation by the kidneys results from decreased ammonium (NH₄⁻) excretion, leading to a fall in bicarbonate
Causes of respiratory alkalosis
Pain, anxiety, psychosis Fever Cerebrovascular accident/stroke Meningitis/encephalitis Trauma
High altitude Pneumonia Pulmonary oedema Aspiration Severe anaemia
Pregnancy, progesterone
Salicylates
Haemothorax, flail chest
Cardiac failure, PE
Septicaemia
Mechanical hyperventilation
Hepatic failure, heat exposure
Metabolic Acidosis
Results from the body producing too much acid or the kidneys failing to excrete enough H⁺.
Initially this creates a decrease in bicarbonate as carbonic acid is produced to buffer the H⁺
The lungs compensate by hyperventilation and blowing of the CO₂
The anion gap can be used to differentiate causes – if gap is normal, bicarbonate is being lost either by GI loss (e.g. diarrhoea) or renal disease allowing loss.
High anion gap results from increased production of acids (e.g. lactic acid, urate or diabetic ketoacidosis) or large amounts of acid (e.g. aspirin overdose)
Causes of metabolic acidosis
HIGH anion gap
Lactic acidosis
Ketoacidosis – diabetic, alcohol abuse, starvation
Renal failure – acute/chronic
Toxins – e.g. methanol, salicylates
NORMAL anion gap
Bicarbonate loss from GI tract
Renal acidosis (proximal/distal tubular acidosis)
Drug-induced (NSAIDs, ACEi, spironolactone, etc)
Rapid saline infusion
Metabolic Alkalosis
Results from increased bicarbonate due to either decreased H⁺ concentration (e.g. due to vomiting) or a direct increase in bicarbonate.
Bicarbonate shift can occur from retention, an intracellular shift in H⁺ or by ingestion of large amounts of alkali (e.g. antacids).
The lungs compensate by slower breathing to retain more CO₂
Causes of metabolic alkalosis
Milk-alkali syndrome Vomiting Nasogastric suction Villous adenoma Hypercalcaemia Recovery from lactic acidosis/ketoacidosis High renin – renal artery stenosis Accelerated hypertension Aldosteronism Cushing’s Syndrome Steroids
ABG - type 1 respiratory failure
PaO2 <10
PaCO2 <6
ABG - type 2 respiratory failure
PaO2 <10
PaCO2 >6
Respiratory History - Dyspnoea
When did it start?
Sudden or gradual?
How long has this been going on for?
can they speak in full sentences?
Is it impacting on day-to-day activities?
How far can they walk?
Does it fluctuate?
Does anything make it better or worse?
Respiratory History - specific PMH
Asthma/COPD or other respiratory conditions
Hx of atopy
Recurrent chest infections in childhood
Respiratory History - relevant drug history
Inhalers – reliever/preventer
Beta-blockers/NSAIDs – bronchoconstriction
ACE inhibitors – dry cough
Cytotoxic agents – interstitial lung disease
Oestrogen – increased risk of PE
Amiodarone/methotrexate – pleural effusions/ interstitial lung disease
Respiratory History - relevant family history
e.g. asthma / atopy / lung cancer / CF
How many cigarettes are 1 pack year?
20 cigarettes/day
Respiratory History - social history
Smoking status - current/past/never
Alcohol
Illicit drugs - cannabis increased risk of lung cancer
Employment - occupational lung disease Hobbies pets (e.g. bird fancier disease)
Overseas travel - long haul flights (PE), TB risk
Ability to complete activities of daily living (ADL)
What type of cells line the respiratory tract normally?
Columnar epithelial cells
How will emphysema appear histologically?
there will be loss of the solid architecture (“moss eaten” appearance)
also unequal size and enlargement of the alveoli (due to dilatation).
What is the difference between congenital and functional alpha1-antitrypsin deficiency?
Congenital - gene defect causes inactivation of antiproteiases
Functional - Smoking causes reactive oxygen species/free radicals, which cause inactivation of antiproteases
Saddle embolism
a large pulmonary embolism that straddles the bifurcation of the pulmonary trunk extending to the left and right pulmonary arteries
What pathogens tend to cause interstitial pneumonia?
The atypical organisms
SARS coronaviruses
What is the most likely organism causing pneumonia in a previously healthy individual?
S. pneumoniae
What is the most likely organism causing pneumonia in pre-existing viral infection?
Staph. aureus or S. pneumoniae
What is the most likely organism causing pneumonia in COPD?
Haemophilus influenzae or S. pneumoniae
What is the most likely organism causing pneumonia in HIV+?
Pneumocystis carinii, cytomegalovirus, TB
What is the most likely organism causing pneumonia in Cystic Fibrosis?
Pseudomonas, Berkholderia species
What is the most likely organism causing pneumonia in a child?
Haemophilus influenzae
What is the most likely organism causing pneumonia in someone who also has a maculopapular skin rash in their extremities?
Mycoplasma pneumoniae
extra-pulmonary manifestations are common
What is the most likely organism causing pneumonia developed during hospital admission?
E. coli, Klebsiella spp., proteus spp., S. pneumoniae, S. aureus (MSSA or MRSA).
what is a the lead time between asbestos exposure and development of mesothelioma?
normally >20 years
which sites does mesothelioma most commonly spread to from the pleural cavity?
other pleural cavity
lung
hilar lymph nodes
what type of room is best to prevent the spread of airborne microbes?
negative pressure isolation room
What is a cavitating lung mass?
what are the causes?
= gas-filled spaces surrounded by consolidation, a lung mass or nodule.
Causes:
- bacterial lung abscess
- metastatic squamous cell carcinoma
- granulomatosis
- pulmonary infarct
what organisms may cause a caveatting lung abscesS?
anaerobic spp.
mycobacterium tuberculosis
