Respiration Flashcards
(243 cards)
1
Q
What is COPD?
A
Disease state characterised by airflow limitation that is not fully reversible
Airflow limitation usually both progressive and associated with an abnormal inflammatory response of lungs in noxious particles or gases
Associated with development of chronic bronchitis and emphysema
2
Q
What causes COPD?
A
Tobacco smoking cause and related to daily average smoked and years smoking
Chronic exposure to - pollutants at work, outdoor pollution, inhalation of smoke from biomass fuels used in heating and cooking in poorly ventilated areas
Rarely symptomatic before middle-age
Alpha-1 antitrypsin
- Early onset COPD
3
Q
What can increase your risk of getting COPD?
A
Age Cigarette smoke Occupational dust and chemicals Environmental tobacco smoke (passive smoking) Indoor and outdoor air pollution Genes Infection Socio-economic status of parents (in utero development) - low birth weight infants with poorly developed lungs
4
Q
What is the pathophysiology of COPD?
A
Increased number of mucus-secreting goblet cells within bronchial mucosa
Bronchi overtly inflamed and pus seen in lumen
Most have emphysema and chronic bronchitis leading to severe airflow limitation
V/Q mismatch partly due to damage and mucus plugging of smaller airways from chronic inflammation and partly due to rapid closure of smaller airways in expiration owing t loss of elastic support
Fall in PaO2 and increase work or respiration
CO2 excretion less affected by V/Q mismatch and many patients have low-normal PaCO2 due to hyperventilation to fix hypoxia
Others fail to maintain respiratory effort and PaCO2 levels increase
Short term - rise in CO2 leads to stimulation of respiration, often become insensitive to CO2 and depend on hypoxaemia to drive ventilation
5
Q
What is the pathophysiology of chronic bronchitis?
A
Airways narrowing and hence airflow limitation due to hypertrophy and hyperplasia of mucus secreting glands of bronchial tree
Bronchial wall inflammation and mucosal oedema
Microscopically - infiltration in walls of bronchi and bronchioles with acute and chronic inflammatory cells
Epithelial layer may become ulcerated and squamous epithelium replaces columnar cells when ulcer heals
Inflammation followed by scarring and thickening of walls narrowing small airways
Small airways particularly affected in early disease - initially no SOB
Initial inflammation reversible and accounts for improvement of airway function if smoking stopped early
Later - inflammation continues even if smoking stopped
Blue bloaters
6
Q
What is the pathophysiology of emphysema?
A
Dilatation and destruction of lung tissue distal to terminal bronchioles
Loss of elastic recoil that normally keeps airways open during expiration
Expiratory flow limitation and air trapping
Loss of alveoli decreases capacity for gas transfer
Pink puffers
7
Q
What are the different types of emphysema?
A
Centri-acinar emphysema - distention and damage of lung tissue concentrated around respiratory bronchioles, more distal alveolar ducts and alveoli tend to be well preseved
Pan-acinar emphysema - distension and destruction affecting whole acinus and in severe cases lung just collection of bullae, associated with alpha-1 antitrypsin deficiency
Irregular emphysema - scarring and damage affecting lung parenchyma patchily, independent of acinar structure
8
Q
What does cigarette smoke do to your lungs?
A
Causes hypertrophy of mucus glands in larger airways and increases neutrophils, macrophages and lymphocytes in airways and walls of bronchi and bronchioles
Release of inflammatory mediators that attract inflammatory cells, induce structural changes and break down connective tissue in lung resulting in emphysema
Inactivates major protease inhibitor alpha-1 antitrypsin
9
Q
How does COPD present?
A
Productive cough with white/clear sputum
Wheeze/SOB
Colds settle on chest
Frequent infective exacerbations with purulent sputum
Symptoms worsened by cold/damp weather and atmospheric pollution
Systemic effects - hypertension, osteoporosis, depression, weight loss, reduced muscle mass with general weakness
Rest with prolonged expiration
Poor chest expansion and hyperinflated lungs
Pursed lips on expiration help prevent alveolar and airway collapse
Later develop respiratory failure - PaO2 < 8 kPa, PaCO2 > 7 kPa
Pulmonary hypertension due to excretion of Na and water by hypoxic kidney
10
Q
What is a possible differential for COPD?
A
Asthma Congestive HF Bronchiectasis Allergic fibrosing alveolitis Pneumoconiosis Asbestosis
11
Q
How is COPD diagnosed?
A
Hx of SOB and sputum production in chronic smoker
Absence of Hx of smoking then asthma more likely unless FHx of alpha-1 antitrypsin deficiency
Lung function tests
- Progressive airflow limitation with increasing severity and SOB
- FEV1 < 80% predicted
- FEV1/FVC < 0.7 (obstruction)
- Stage 1 - FEV1 < 80%
- Stage 2 - FEV1 50-79%
- Stage 3 - FEV1 30-49%
- Stage 4 - FEV1 < 30%
- Multiple peak flow measurements needed to exclude asthma
CXR
- May be normal or show evidence of hyperinflated lungs indicated by low, flattened diaphragm and long narrow heart shadow
- Reduced peripheral lung markings
High res CT
Hb and PCV high due to persistent hypoxaemia and secondary polycythaemia
ABGs normal/hypoxia with/without hypercapnia
ECG normal
Alpha-1 antitrypin levels and genotypes
12
Q
How is COPD treated?
A
Smoking cessation - slow rate of deterioration and prolong time before disability and death
Bronchodilators
- Inhaled tiotropium bromide (long acting muscarinic agent) with rescue short-acting B2 agonist
- Long acting B2 agonist if SOB
Corticosteroids
- Prednisolone for 2 wks with measurements of lung function before and after treatment period
- If improved then discontinue prednisolone and move to inhaled corticosteroid
Prevention of infection
- Exacerbations often due to bacterial or viral infection
- Pneumococcal vaccine and annual flu vaccine
- Prompt antibiotic treatment
O2 therapy
- For patients who no longer smoke
- O2 for 19 hrs per day, every day via nasal prongs to increase PaO2 > 90%
Anti-mucolytic agents
Diuretics
Pulmonary rehabilitation to increase exercise capacity with diminished sense of SOB and improved general well being
Good diet to reduce weight and obesity
Alpha-1 antitrypsin replacement
13
Q
What is asthma?
A
Chronic condition whose cause is incompletely understood
14
Q
How common is asthma?
A
Commonly starts in childhood between 3-5 and may either worsen or improve during adolescence
Peak prevalence 5-15
More common in developed countried
15
Q
What are the different types of asthma?
A
Allergic/eosinophilic (70%) - allergens and atophy
- Extrinsic (atopic) - childhood asthma often accompanied with asthma
- Intrinsic - often starts in middle age and attacks usually triggered by respiratory infections, often had extrinsic asthma as a child, positive allergen skin tests, or caused by sensitisation to occupational agents eg toluene, diisocyanate, intoleracne to NSAIDs
Non-allergic/non-eosinophilic (30%)
- Exercise, cold air, stress
- Smoking and non-smoking associated
- Obesity associated
16
Q
What can cause asthma?
A
Genetics - several genes in combination with environmental factors, genes controlling production of cytokines IL3, 4, 5, 9 and 13, ADAM33 associated with airway hyerpresponsiveness and tissue remodelling
Environmental factors - early childhood exposure to allergens and maternal smoking has influence on IgE production, growing up in clean environment may predispose towards IgE response to allergens
17
Q
What can increase your risk of getting asthma?
A
Personal Hx of atopy FHx of asthma or atopy Obesity Inner-city environment Premature birth Socio-economic deprivation
18
Q
What is the pathophysiology of asthma?
A
Airflow limitation - usually reversible spontaneously or with treatment
Airway hyper-responsiveness
Bronchial inflammation with T lymphocytes, mast cells, eosinophils and associated with plasma exudation, oedema, smooth muscle hypertrophy, mucus plugging and epithelial damage
Atopy - IgE developed against common environmental antigens such as house-dust mites, grass pollen, fungal spores
Serum IgE levels affected by several genetic and environmental factors
Primary abnormality - narrowing of airway die to SM contraction, thickening of airway wall by cellular infiltration and inflammation and presence of secretions within airway lumen
19
Q
What are the precipitating factors of asthma?
A
Occupational sensitisers - wood dust, bleaches, dyes, isocyanates, latex
Cold air and exercise
Atmospheric pollution and irritant dusts
Diet - more fruit and veg protective
Emotion - high risk asthma attacks in anxious individuals
Drugs - NSAIDs, beta-blockers direct parasympathetic innervation resulting in bronchoconstriction
Allergen induced asthma
20
Q
What causes inflammation in asthma?
A
Mast cells - increased in epithelium, SM and mucous glands, sensitised when IgE binds to mast cell receptor and mast cell responds to allergen if allergen on IgE
Mast cell releases histamine within seconds resulting in bronchoconstriction and inflammation, tryptase, prostaglandin 2 within minutes, cysteine leukotirens within minutes and more potent that histamine, cytokines TNF-alpha, IL-3, 4 and 5 within hours increasing the number of mast cells resulting in inflammation and airway remodelling
All act on SM, small vessels, mucus secreting cells and sensory nerves causing immediate asthmatic reaction
Eosinophils - in bronchial wall and secretions, attracted to airways by IL3 and 5
Release LTC4 and proteins that are toxic to epithelial cells
Number and activity decreased by corticosteroids
Dendritic cells and lymphocytes in mucous membranes and alveoli
Dendritic cells APCs to lymphocytes of allergen
T helper lymphocytes activate and release cytokines key in mast cell activation
21
Q
What changes are there in the lung after challenge from allergen?
A
30 mins - bronchoconstriction
3 hours - initial bronchoconstriction decreases, inflammation occurs due to vasodilation which decreases blood flow leading to build up of WCC, increased vascular permeability and unregulated adhesion molecules
6 hours - worsening inflammation resulting in eosinophils releasing mediators resulting in second wave of bronchoconstriction
22
Q
How does the airway remodel after an asthma attack?
A
Characteristic feature of chronic asthma alteration of structure and function of formed elements of airways
SM hypertrophy and hyperplasia so larger fraction of wall SM
Thickening of wall by deposition of repair collagens and matrix proteins below BM
Expansion of submucosa due to deposition of matrix proteins, swelling and cellular infiltration so for every degree of SM shortening excess airway narrowing
Epithelium stressed and damaged with loss of ciliated columnar cells
Metaplasia occurs with increase in number of mucus secreting goblet cells
Damage to epithelium makes it more vulnerable to infection
23
Q
How does asthma present?
A
Intermittent SOB
Wheeze
Cough especially nocturnal
Sputum
Symptoms worse at night
Provoking factors - allergens, infections, menstrual cycle, exercise, cold air
During attack - reduced chest expansion, prolonged expiratory, time, bilateral expiratory polyphonic wheezes, tachypnoea
Uncontrolled asthma PEFR < 50%, RR < 25, pulse < 1000, normal speech
Severe attack - inability to complete sentences, pulse > 100, RR > 25
Life threatening attack - silent chest, confusion, exhaustion, cyanosis PaO2 < 8 kPa, bradycardia, PEFR < 33%
24
Q
What is a possible differential diagnosis of asthma?
A
Pulmonary oedema COPD (may co-exist) Large airway obstruction caused by foreign body/tumour Pneumothorax Bronchiectasis
25
How is asthma diagnosed?
RCP3 Qs - recent nocturnal waking, usual asthma symptoms in a day, interference with activities of daily living
Asthma control test - 25 well controlled, 20-24 on target, < 20 off target
Lung function tests - PEFR (on waling, prior to taking bronchodilator and before bed after taking bronchodilator), spirometry, CO test normal, must be > 15% improvement of FEV1 or PEFR on bronchodilator inhalation
Exercise tests
Trail or corticosteroids
Exhaled NO - measures eosinophilic inflammation and index of corticosteroid response
Blood and sputum tests - increased eosinophils in peripheral blood, sputum eosinophilia more specific
Hx tells a lot
Distinguish from COPD
- Later disease and dominated by smokers
- Relentless progressive SOB with wheeze
- Less day-to-day variation
- Winter symptoms and sputum production
- Overlap possible
26
What is the immediate management of an asthma attack?
O2 therapy to maintain O2 94-98%
Nebulised 5mg salbutamol - repeat/IV infusion
Prednisolone with/without hydrocortisone IV
ABGs and repeat within 2 hours if severe attack/patient deteriorating
CXR if fails to respond
PEFR within 15-30 mins/regularly
Oximetry to ensure SaO2 > 92%
27
What are the aims of asthma treatment?
Abolish symptoms
Restore normal/best possible lung function
Reduce risk of severe attacks
Enable normal growth to occur in children
Minimise absence from school/employment, patient and family education about asthma and treatment
Avoidance of identified causes if possible
Use of lowest effective doses of medication to minimise short-term and long-term side effects
28
How is asthma treated?
```
Control of extrinsic factors when specific allergen triggers identified
Bronchodilators
- Beta-2 agonists
- Long acting beta agonists
- Muscarinic antagonists
- Methylxanthines
Anti-inflammatory steroids
Other agents
- Leukotriene receptor antagonist
- Oral corticosteroid for those not controlled on inhaled
Steroid sparing agents
- Methotrexate
- Ciclosporin
- IV immunoglobulin
- Anti-IgE monoclonal antibody
```
29
How common is bronchial carcinoma?
Most common malignant tumour worldwide with around 1.4 million deaths annually
3rd most common cause of death in UK after IHD and CVD
Slightly more common in men than women but incidence in women increasing due to smoking habits
30
What are the two main types of bronchial carinoma?
```
Small cell lung carcinoma
Non-small cell
- Squamous carcinoma
- Adenocarcinoma
- Large cell and differentiated carcinoma
- Carcinoid tumours
Difference of histological phenotype
Distinction necessary with respect to behaviour of tumour, providing prognostic information and determining best treatment
```
31
What can increase your risk of bronchial carcinoma?
```
Cigarette smoking (including passive) 90%
Occupational
- Asbestos
- Coal and products of coal combustion
- Chromium
- Arsenic
- Nickel
- Petroleum products
- Iron oxide
Environmental
- Radon exposure
- Ionising radiation
Host factors
- Pre-existing lung disease such as pulmonary fibrosis
- HIV infection
- Genetic factors
```
32
What is the pathology of small cell lung carcinoma?
```
Strongly associated with cigarette smoking
Often spread by time of presentation
Often arises in central bronchus
Arises from endocrine cells
Secretes polypeptide hormones
Early development of widespread metastases
Chemotherapy primary treatment
Poor prognosis
```
33
What is the pathology of non-small cell lung carcinoma?
Associated with cigarette smoking
May have metastasised by time of diagnosis
Often treated best by surgical ablation with lymph node sampling
Chemotherapy and radiotherapy
More susceptible to new therapy such as tyrosine kinase therapy
34
What is the pathology of squamous cell carcinoma?
Most strongly associated with cigarette smoking
Tumours usually central location and frequently cavitate with central necrosis
Arise from epithelial cells, associated with production of keratin
Cause obstructive lesions of bronchus with post-operative infection
Local spread common
Metastasise relatively late
35
What is the pathology of adenocarcinoma?
Most common
Central/peripheral
Single lesions but can be multi-focal pattern, sometimes bilaterally
Originate from mucus secreting glandular cells
Most common cell type in non-smokers
Often cause peripheral lesions on CXR/CT
Metastases common especially to pleura. lymph nodes, brain, bones, adrenal glands
Associated with asbestos
36
What is the pathology of carcinoid tumours?
Present at earlier age and have characteristic neuroendocrine secreting cells and relatively low rate of invasion and growth
Still malignant
37
What is the pathology of lymphomas in the lung?
Involve lung primarily but usually part of disseminated disease
Main lung lymphoma BALTOMA - bronchus associated tissue lymphoma, B cell lymphoma and responds to chemo
38
What is the pathology and name of a benign lung tumour?
Hartoma
Irregular proliferations of benign/normal tissues not normally found in this pattern in lung tissue, commonest chondroid harmartoma that incorporated cartilage, glandular tissue, fat fibrous tissue and blood vessels
39
What sites can lung cancer metastasise to?
Liver - anorexia, nausea, weight loss, RUQ pain radiating across abdomen
Bone - bony pain and pathological fractures
Adrenals - asymptomatic
Brain - space occupying lesion
Spread within chest and involve pleura and ribs resulting in pain and fractures
40
What cancers can spread to lung?
```
More common than lung metastasising elsewhere
Breast
Bowel
Kidney (most common)
Bladder
```
41
What are the symptoms of bronchial carinoma?
```
Cough 3 wks merits CXR
SOB on exertion
Haemoptysis
Chest pain
Wheeze
Recurrent infections
Clubbing
Metastatic disease - bone pain, headache, seizure, neurological deficit, hepatic pain, abdominal pain
Paraneoplastic changes (10%) - secretion of PTH, SIADH, secretion of ACTH, hypertrophic pulmonary osteoarthropthy, finger clubbing, non-infective endocarditis, DIC
```
42
What is the TNM classification for bronchial carcinoma?
T1 < 3cm
T2 > 3cm
T3 invasion of chest wall, diaphragm and pericardium
T4 invasion of mediastinum, heart, great vessels, trachea, oesophagus, vertebrae, carina, malignant effusion, metastases in same lobe
N0 no nodes
N1 hilar nodes
N2 same side mediastinal nodes of subcarinal
N3 contralateral mediastinal nodes/supraclavicular
M1a tumour of same side
M1b tumour elsewhere
43
How is bronchial carinoma diagnosed?
CXR - round shadow, edge has fluffy, spiked appearance, hilar enlargement, consolidation, lung collapse, pleural effusion
CT for staging
Bronchoscopy for histology and assessing operability +/- endobronchial USS for assessment and biopsy
Cytology sputum and pleural fluid
Bloods FBC
44
How is non-small cell lung carcinoma treated?
Surgical excision for peripheral tumours with no metastatic spread
Curative radiotherapy for alternative if respiratory reserve poor
Chemotherapy +/- radiotherapy for more advanced disease with monoclonal antibodies targeting epidermal growth factors receptor
45
How is small cell lung carcinoma treated?
Chemo and radiotherapy
Extensive - chemo
Usually relapse
Palliation to relieve symptoms radiotherapy for bronchial obstruction, haemoptysis, bone pain, cerebral metastases
SVC stent and radiotherapy and dexamethasone for SVC obstruction
Endobronchial therapy - trachial stenting, cryotherapy, brachytherapy for airway narrowing
Pleural drainage
Analgesia, steroids, antiemetics, codeine, bronchodilators, antidepressants
46
What can cause a pulmonary embolism?
```
Clots breaking off, passing through veins to IVC then into right side of heart before lodging in pulmonary circulation
R ventricular thrombus
Septic emboli
Fat embolus
Air embolism
Amniotic fluid embolism
Neoplastic cells
Parasites
Foreign material during IV drug misuse
```
47
What can increase your risk of a pulmonary embolism?
```
Change in blood flow
- Immobility, obesity, pregnancy
Change in blood vessel
- Smoking, hypertension
Change in blood constituents
- Dehydration, malignancy, high oestrogen, polycythaemia, nephrotic syndrome, inherited
Recent surgery especially abdominal/pelvic/hip or knee replacement
Leg fracture
> 60 years
```
48
What is the pathology of pulmonary embolism?
Circulatory stasis, endothelial injury and hypercoagulable states predispose you to clot
Arise from venous thrombus in pelvis/legs
Clot breaks off and passes through veins -> IVC -> RA -> RV -> pulmonary circulation where lodged in small capillaries supplying alveoli resulting in PE
Lung tissue ventilated but not perfused so intrapulmonary dead space and impaired gas exchange
After a few hours, non-perfused lung no longer produces surfactant resulting in alveolar collapse exaggerating hypoxaemia
Primary haemodynaic consequence is reduction in cross-sectional area of pulmonary bed causing elevation in pulmonary arterial pressure due to increased resistance and reduction in CO
RV ischaemia detected with elevations of troponin and creatinine kinase
Associated with adverse outcomes
Small emboli in more distal/terminal vessels can be clinically silent unless lead to infarction
49
How does PE present?
```
Depends on number/size/distribution of emboli
Large often fatal
Sudden onset, unexplained SOB
Pleuritic chest pain
Haemoptysis
Dizziness
Risk factors
Past/FHx
Pyrexia
Cyanosis
Tachypnoea/tachycardia
Hypotension
Raised JVP
Pleural rub/effusion
```
50
What is a possible differential diagnosis of PE?
```
Asthma
COPD
MI
Pneumonia
HF
```
51
How is PE diagnosed?
CXR
- Often normal
- Decreased vascular markings, blunting of costophrenic angle, wedge shaped areas of infarction, pulmonary oligaemia
- Make sure not MI/pneumothorax
ECG
- Sinus tachycardia, R atrial dilation (small peaked P waves in lead II), RBBB, R ventricular strain (inverted T wave in V1-4)
Blood gases - hypoxiaemia T1 resp failure
Plasma D dimer
USS of leg and pelvis looking for clots
CT pulmonary angiography
52
How is PE treated?
High flow O2 (60-100%) not if significant lung disease
Anticoagulated with LMW heparin
IV fluids and inotrophic agents
Thrombolysis
Surgical embolectomy
VC filter in those who develop PE even on anticoagulation
53
How do you prevent PE long term?
Vitamin K antagonist
Target INR between 2-3
Patients mobilised
TED stockings
54
How is a massive PE managed?
Oxygen if hypoxic
Morphine
Antiemetic
Immediate thrombolysis if critically ill
IV access for heparin
Systolic BP < 90mmHg rapid colloid infusion, still low dobutamine, still low noradrenaline, still low after 30-60 mins definitely PE begin thrombolysis
Systolic BP > 90mmHg warfarin and confirm diagnosis
55
What is acute epiglottistis?
Epiglottis inflammation
56
What can cause acute epiglottitis?
Adults - most severe H influenzae, also from causes of pharyngitits, additional pathogens in immunocompromsied
Rare due to Hib vaccine
57
How does acute epiglottitis present?
```
High fever
Severe airflow obstruction
Meningitis
Septic arthritis
Osteomyeltitis
```
58
How is acute epiglottitis treated?
Urgent endotracheal intubation
| IV antibiotics ceftazidime
59
What is croup?
Occasional complication of upper respiratory tract infections
Particularly those caused by parainfluenza viruses and measles
Acute laryngotracheobronchitis
60
What causes croup?
Parainfluenza viruses
| Most severe in children under 3
61
What is the pathology of croup?
Inflammatory oedema extends to vocal cords and epiglottis causing narrowing of airway
Progressive airway obstruction with recession of soft tissue of neck and abdomen during inspiration and in severe cases central cyanosis
62
How does croup present?
Voice hoarse with barking cough
Audible stridor (high pitched wheeze on inspiration)
Febrile - high RR and cyanosis
Intercostal recession
63
How is croup treated?
Nebulised adrenaline for short term relief
| Oral/IM corticosteroids eg dexamethasone with O2 and fluids
64
What is pharyngitis?
Infection of throat
65
What is tonsilitis?
Infection of tonsils
66
What can cause pharyngitis and tonsilitis?
Most common viral cause adenoviruses of which 32 serotypes
Rhinovirus, EBV, acute HIV infection
Lancefield group A beta-haemolytic streptococci
67
How does pharyngitis and tonsilitis present?
```
Sore throat
Tender glands in neck
Fever
Stable vital signs
Large tonsils with exudate
Tender anterior cervical lymph nodes enlarged within 1-2 days
Oropharynx and soft palate reddened
```
68
How is pharyngitis and tonsilitis treated?
Self-limiting disease
Symptomatic treatment
No antibiotic required
Persistent and severe tonsilitis treated with phenoxylmethylpenicillin or cefaclor
69
What can cause respiratory viral infections?
Rhinovirus - common cold, bronchitis, sinusitis
Influenza A virus- flu
Coronaviruses - colds but occasionally sever respiratory illnesses
Adenoviruses - upper respiratory tract infection, pharyngitis, bronchitis and occasionally pneumonia
Respiratory syncytial viruses - bronchiolitis in young children, severe illness in nursing home residents and pneumonia in immunocompromised
70
What can cause emergency respiratory infections?
SARS
- Coronavirus
- Outbreak from China
- Severe respiratory illness with respiratory failure
MERS-nCV
- Middle East
- Similar to SARS but low person to person spread
Avian inflenza
- Novel form of Influenza A
- Occasional human cases with severe illness
- Seen in South Asia associated with poultry exposure
- Low person to person spread
71
What are the complications of respiratory viral infections?
```
Pharyngitis
Sinusitis
Otitis media
Bronchitis
Pneumonia
Bacterial superinfection
```
72
What is sinustitis?
Infection of paranasal sinuses that is bacterial or occasionally fungal
73
What causes sinustitis/
Bacterial - streptococcus pneumoniae (40%), H influenzae (30-35%)
74
How does sinustitis present?
Fever, facial pain with tenderness, purulent nasal discharge
Frontal headache
Purulent rhinorrhoea
Bacterial sinusitis - unilateral pain and purulent discharge with/without fever for more than 10 days
75
How is sinusitis treated?
Nasal decongestants = xylometazoline
| Broad spectrum antibiotics such as co-amoxiclav
76
What are the possible complications of sinusitis?
Brain abscess
Sinus vein thrombosis
Orbital cellulitis
77
What is whooping cough?
Bordatella pertussis - gram negative coccobacillus
| Bordatella parapertussis and bronchiseptica produce milder infections
78
When is whooping cough most common?
Childhood 90% cases are under 5
| No age exempt as antibody levels fall over years
79
What is the pathology of whooping cough?
Highly contagious
Spread by droplet infection
In early stages, indistinguishable from other upper respiratory tract infections
Multiple virulence factors
- Filamentous haemagglutinin and fimbrae aid adherence
- Adenylate cyclase toxin inhibits phagocyte chemotaxis and T cell activation
- Pertussis toxin A/B toxin that ADP ribosylates G proteins and inhibits alveolar macrophage host defence
- Tracheal cytotoxin and dermonectroic toxin cause epithelial necrosis
Lymphoid hyperplasia and Th17 skewing of immune response contributes to inflammation and cough
80
How does whooping cough present?
```
Chronic cough
Febrile
Sub-conjuntival haemorrhage
Catarrhal phase (1-2 wks)
- Highly infectious
- Cultures from respiratory cultures positive in 90% cases
- Malaise
- Anorexia
- Rhinorrhoea
- Conjuntivitis
Paroxysmal phase (1-6 wks)
- Coughing spasms
- 1 wk after catarrhal phase
- Classic inspiratory whoop in younger people with compromised respiratory tract with mucous secretion and oedema
- Coughing spasms terminated in vomiting
- Cough for more than 14 days
- Associated with complications - pneumonia, encephalopathy, sub-conjuntival haemorrhage
```
81
How is whooping cough diagnosed?
Chronic cough with one clinical feature indicating pertussis
Chronic cough with Hx of contact/microbial diagnosis
Suggested clinically by whoop and Hx of contact with infected individual
PCR test
Culture of nasopharyngeal swab for definitive diagnosis
82
How is whooping cough treated?
Antimicrobials such as macrolides (clarithromycin) eliminate carriage of bacteria and reduce symptoms in catarrhal stage and early paroxysmal
In paroxysmal - antibiotics play little role
Vaccination - acellular pertussis part of dTap vaccine (diptheria, tetanus and acellular pertussis) at 2, 3, 4 months and 3-4 years
83
What is pneumonia?
Inflammation of substance in lungs
Acute lower respiratory tract infection
Usually caused by bacteria but can also be caused by viruses and fungi
Usually due to infection affecting distal airways and alveoli with formation of inflammation exudate
84
What is community acquired pneumonia?
No underlying immunosuppression or malignancy
Occurs across all ages but commoner at extremes
Primary/secondary to underlying disease
Streptococcus pneumoniae commonest cause
Rarer - S aureus, Legionella spp, Moraxella cararrhalis, Chlamydia (not susceptible to beta-lactams)
Infection can be localised
Can be diffuse when lobules of lungs mainly affected, often due to infection centred on bronchi and bronchioles - bronchopneumonia
85
What is hospital acquired pneumonia?
New onset cough with purulent sputum along with completeable x-ray demsonstrating consolidation in patients beyond 48 hrs initial admission or been in healthcare setting in last 3 months
Elderly, ventilator associated and post-operative
HAP second most common hospital acquired infection after UTI
Aerobic gram-negative bacilli - P aerguinosa, E coli, K pneumoniae
S aureus particularly MRSA
HAP due to S aureus more common in patients with DM or head trauma and those in ITU
86
What are the causes of pneumonia in immunocompromised patients?
Unusual organisms and opportunistic pathogens
Symptoms may resemble CAP or be non-specific
Pneumocystitis jiroveci most common
87
What is aspiration pneumonia?
Acute aspiration of gastric contents into lungs
Severe sometimes fatal due to intense destructiveness of gastric acid
Seen in those with stroke, myasthenia gravis, bulbar palsies and lack of consciousness
Can complicated anaesthesia, particularly pregnancy
88
What can cause CAP?
S pneumoniae
H influenzae
Atypical - mycoplasma pneumoniae, Chlamydia pneumoniae
Enteric gram negative bacteria E coli, K pneumoniae
89
What can increase your risk of getting pneumonia?
```
Under 16
Over 65
Co-morbidities - HIV infection, DM, CF, COPD, bronchiectais
Excess alcohol
Smoking
IVDU
Immunosuppressant therapy
```
90
What is the pathology of pneumonia?
Spread by respiratory droplets
Pneumococcal pneumonia typically acute in onset with prominent respiratory symptoms and fever
Atypical pathogens tend to have slower onset with more prominent extra-pulmonary symptoms and complications
Do not respond to penicillin as lack cell wall
Translocate to normally sterile airway
Overwhelm resident host defence
Alveolar macrophages ingest bacteria and produce hormonal factors
Antibodies produces with mircobial factros and bacteria destroyed
Host defences overwhelmed and alveolar macrophages change roles and instead co-ordinate response
Stimulate neutrophils to fill alveolar space and produce pus
Normally resolved and bacteria cleared with inflammatory cells being removed by apoptosis
Severe disease results if excessive inflammation, lung injury, failure to resolve without lung damage
91
How does pneumonia present?
```
Symptoms of fever, night sweats, raised RR, productive cough and absence of URT symptoms
Low BP
Rigors
Malaise and anorexia
SOB - alveoli filled with pus and debris, imparing gas exchange, coarse crackles on ascultation due to consolidation of lung parenchyma
Signs of consolidation
- Dull to percussion
- Decreased air entry
- Bronchial breath sounds
Dry productive cough
Purulent sputum
Pleuritic chest pain
Cyanosis
Confusion
```
92
What is a differential diagnosis of pneumonia?
TB
| Lung cancer
93
How is pneumonia diagnosed?
CXR - radiological abnormalities can lag behind clinical findings
- Normal CXR repeated after 2-3 days if CAP suspected
- Air bronchogram in consolidated areas
- Multi-lobar (S pneumoniae, S aureus, Legionella)
- Multiple abscesses S aureus
- Upper lobe cavity then K pneumoniae must exclude TB
Bloods
- FBC - WBC elevated in S pneumoniae, marker of severity
- ESR/CRP raised
Biochemisty - U&Es and LFTs
Pulse oximetry and ABGs if O2 < 94%
HIV tests
Microbial tests
- Sputum culture and antibiotic sensitivities +/- gram stain
- Blood culture
- Serology for viruses and atypical organisms
CURB65 to assess severity of CAP
94
What is CURB65?
One point for each
- Confusion
- Urea > 7mmol/L
- RR > 30/min
- BP < 90mmHg systolic and/or 60mmHg diastolic
- Age > 65
Implications
- 0-1 mild only admit if social circumstances/single worrying feature
- 2 moderate admit
- 3-5 severe, admit and monitor closely
- 4-5 consider admission to critical care
95
How is pneumonia treated?
Maintain O2 sats between 94-98%
In COPD 88-92%
First dose antibiotics administered within 4 hrs presentation in hospital and treatment not delayed whilst investigations underway
Analgesia - paracetamol/NSAIDs for pleuritic chest pain
Narrow spectrum antimicrobials if mild amoxicillin 5-7 days
IV antibiotics if severe co-amoxiclav/clarithromycin 7-10 days
Special cases
- Legionella fluoroquinolone (ciprofloxacin) with/without clarithromycin
- Necrotising pneumonia - IV linezolid, clindamycin, rifampicin
- Pseudomonas aeruginosa IV ceftazidime with gentamycin/tobramycin
96
How do you prevent pneumonia?
Polysaccharide pneumococcal vaccine
Influenza vaccine for those > 65, immunocompromised or with medical co-morbidities
Smoking cessation
97
What are the complications of pneumonia?
Respiratory failure
Hypotension - dehydration and vasodilation due to sepsis
Parapneumonic effusion and empyema
Lung absecesses
98
How common is TB?
```
1/3 world's population infected
9 million cases per year with 2 million deaths
Global incidence on decline
Majority cases in Africa and Asia
Cause of death of most people with HIV
```
99
What are the main causes of TB?
Mycobacterium tuberculosis
Mycobacterium bovis
Mycobacterium africanum
Mycobacterium microti
100
What are the characteristics of mycobacterium causing TB?
Aerobic, non-motile, non-sporing, slightly curved bacilli with thick waxy capsule
Acid-fast bacilli - go red/pink with Ziehl-Neelsen stain
Only stain weakly with gram stain due to high cell wall lipid content
Slow growing - generation time 15-20 hours
Resistant to phagolysosomal killing by macrophages hence granulomata
Able to remain dormant
101
What can increase your risk of getting TB?
```
Origination from high incidence country eg Sub-Saharan Africa
HIV +
Immunosuppressant therapy
DM
IVDU
Ageing
Malnutrition
Homeless - poverty
Prisons
Smoking
Alcohol
```
102
How do you get infected with TB?
Airborne infection spread via droplets
Only small number of bacteria need to be inhaled for infection to develop
Not all infected actually develop disease
Outcome of exposure dictated by number of factors including host's immune response
Upon initial contact with infection less than 5% develop disease
Increases by 10% within first year of exposure
103
What is primary tuberculosis and what is its pathology?
First infection of TB
Once inhaled into lung, alveolar macrophages ingest bacteria
Bacilli proliferate inside macrophages and cause release of neutrophil chemoattractants and cytokines resulting in inflammatory cell infiltrate reaching lung and draining hilar lymph nodes
Macrophages present antigen to T lymphocytes with development of cellular immune response
Delayed hypersensitivity reaction resulting in tissue necrosis and granuloma formation
Lymphocytes present and varying degree of fibrosis
Initial granuloma = Ghon focus in upper sub pleural region
Primary lesion can also occur in GI tract
Bacilli taken into lymph nodes where secondary lesions develop
Caveated areas heal completely and may become calcified
Some calcified nodules contain bacteria which are contained by immune system and hypoxic acidic environment created within granuloma capable of lying dormant for many years
If bacteria cannot be contained and dissemination of primary infection can lead to miliary TB where TB spreads to other organs
104
What is latent TB?
In majority of people who are infected, immune system contains infection and patient develops cell mediated immunity memory of bacteria
105
What is reactivation TB?
Majority cases due to reactivation of latent infection - post-primary TB usually when there is depression of host immune system
Initial contact usually occurred many years earlier
In patients with HIV, newly acquired TB common
106
What are the other types of TB?
```
GI
Bone and spine
Miliary
CNS
Pericardial
Skin
```
107
What are the systemic features of TB?
```
Weight loss
Low grade fever
Anorexia
Night sweats
Malaise
```
108
What are the symptoms of pulmonary TB?
Productive cough with occasional haemoptysis
Cough > 3 weeks
Pleuritis pain if pleural involvement
Chest pain
SOB
Hoarse voice if laryngeal involvement
Associated with - consolidation, pleural effusion, pulmonary collapse caused by compression of lobar bronchus by enlarged lymph nodes
109
How does extra-pulmonary TB present?
Lymph node TB - swelling +/- discharge
Bone TB - pain or swelling of joint, potts disease
Abdominal TB - ascites, abdominal lymph nodes, ileal malabsorption
GU TB - epididymitis, frequency, dysuria, haematuria
CNS - bacilli in CSF and on meninges, meningeal inflammation produces thick exudate leading to strangulation of CNs and raised ICP, low grade meningitis, random cranial palsies and symptoms of raised ICP, headache, vomiting, confusion, coma
110
How is TB diagnosed?
CXR
- Patchy or nodular shadows in upper zones with loss of volume and fibrosis with/without cavitation
- Consolidation
- Miliary TB CXR may be normal or show milary shadows
Sputum
- Stained with auramine-phenol fluorescent test highlighting bacilli yellow/orange on green background
- Ziehl-Neelsen stain for acid- and alcohol-fast bacilli
Bronchoscopy if no sputum
Histology - caseating granuloma
Culture
- Liquid/broth cultures
- Solid culture on Lowenstein-Jensen slopes or Middlebrook agar
Nucleic acid amplification
Lumbar puncture and CSF examination
111
How is latent TB diagnosed?
Tuberculin skin test Matnoux
| Interferon gamma release assays
112
How is TB treated?
Notify PHE
If histology and culture picture consistent with TB then start treatment without waiting for culture results and continue even if negative
Contact tracing
6 months treatment - if CNS 12
- Rifampicin for 6 months (bactericidal, blocks protein synthesisi, S/E red urine, hepatitis, drug interactions (OCP))
- Isoniazid 6 months (bactericidal for rapidly growing bacilli, most effective in initial stages, S/E hepatitis, neuropathy)
- Pyrazinamide for 2 months (bactericidal initially, less effective later, S/E hepatitis, arthralgia/gout, rash)
- Ethambutol for 2 months (bacteriostatic, blocks cell wall synthesis, S/E optic neuritis)
Compliance critical to reduce relapse and resistance
DOTS clinics to give medication under supervision
TB nurses
113
How is TB prevented?
Active case finding to reduce infectivity
Detection and treatment of TB via community nursing team using matoux and IGRAs
Vaccination
- Neonatal BCG - live attenuated vaccine, variable efficacy by recommended in neonates from high risk groups
114
What is bronchiectasis?
Chronic infection of bronchi and bronchioles leading to permanent dilatation of these airways
Results from pulmonary inflammation and scarring due to infection, bronchial obstruction or lung fibrosis
Bronchial walls become inflamed, thickened and irreversibly damaged
Mucociliary escalator impaired and therefore frequent bacterial infections
Clinically disease characterised by productive cough with large amounts of discoloured sputum and dilated, thickened bronchi detected on CT
115
How common is bronchiectasis?
More common in women
May develop after lung infections
Pathological end point of many diseases
Present at any age but increases with age
116
What can cause bronchiectasis?
```
Arises as a result of chronic inflammation that damages the alveolar lung around the airways and airway walls resulting in scarring causing airway distortion and dilatation with further inflammatory process in wall of damaged airway due to secondary infection
Post-infection (most common)
- Previous pneumonia
- Granulomatous disease (TB)
- Measles, whooping cough
- Allergic broncho-pulmonary aspergillosis
- Bronchiolitis
Congenital
- Cystic fibrosis
- Deficiency of bronchial elements
- Primary ciliary duskinesia
Mechanical bronchial wall obstruction
- Foreign body
- Post TB stenosis
- Lymph node/tumour
HIV
UC
Hypogammaglobulinaemia
RA
```
117
What is the pathology of bronchiectasis?
Failure of mucociliary clearance and impaired immune function contribute to continued insult of bronchial wall, through recruitment of inflammatory cells and uncontrolled neutrophilic inflammation
Bronchitis -> bronchiectasis -> fibrosis
Airways dilate due to pulmonary inflammation and scarring as fibrosis contracts
Secondary inflammation changes lead to further destruction of airways
118
How does bronchiectasis present?
Usually affects lower lobes
Chronic cough with production of copious amounts of foul-smelling purulent sputum
Dyspnoea
Finger clubbing especially with CF
Wheeze
Infection usually characterised by increased sputum volume and increased purulence
Chest pain
Recurrent exacerbations with long recovery time
119
What is a possible differential of bronchiectasis?
```
COPD
Asthma
TB
Chronic sinusitis
Cough due to acid reflux
Pneumonia
Pulmonary fibrosis
Cancer
Inhalation of foreign body
```
120
How is bronchiectasis diagnosed?
CXR
- Dilated bronchi with thickened walls
- Multiple cysts containing fluid showing up as cystic shadows
Sputum culture
- See bacterial colonisation status
- Major pathogens - H influenzae, S pneumoniae, S aureus, P aeruginosa
- Used to exclude non-tuberculous mycobacterial disease
High resolution CT
- Thickened, dilated bronchi with cysts at end of bronchioles
- Airways larger than associated blood vessels
Spirometry - obstructive pattern
Sinus x-rays 30% patients also have rhinosinusists
Sweat test for all patients under 40 if suspected CF
Bronchoscopy to locate site of haemoptysis, exclue obstruction and obtain culture samples
Immunology - total IgE to exclude bronchopulmonary aspergillosis
121
How is bronchiectasis treated?
Improved mucus clearance
- Postural drainage
- Chest physio
- Mucolytics
Antibiotics
- Treatment of exacerbations for 2 wks
- If P aerguinosa then high dose ciprofloxacin 2x daily
- H influenzae oral amoxicillin/co-amoxiclav/doycycline, some multi-resistant species need cephalosporin
- If S aureus flucloxacillin
Bronchodilators - nebulised salbutamol for asthma or COPD
Anti-inflammatory agents - long term azithromycin can reduce exacerbation frequency
Surgery in localised disease or to control severe haemoptysis
122
What is cystic fibrosis?
One of the most common lethal autosomal recessive conditions in Caucasians
25% condition and 50% carrier risk
123
How common is CF?
Much less common in Afro-Caribbean and Asian populations
Multi-system disease although respiratory problems usually most prominent
Most people with CF also have pancreatic insufficiency
124
What can increase your risk of getting CF?
FHx
| Caucasian
125
What is the pathology of CF?
CF gene on long arm of chromosome 7 coding for CF transmembrane regulator protein
CFTR acts as chloride channel and normally transports negative ions and Na+ passively follows causing osmostic gradient and movement of water out of cell and into mucus
Commonest mutation F508 deletion 70%
80% lung and GI involvement
15% lung
In lungs, CFTR dysfunction leads to dehydrated airway surface liquid, mucus stasis, airway inflammation and recurrent infection
Changes in composition of airway surface liquid predisposes lung to chronic pulmonary infections
Process originates in small airways - progressive airway obstruction and bronchiectasis
126
How does CF present?
Multi-system but main cause of death related to respiratory disease
Lungs of babies with CF structurally normal at birth, frequent respiratory infections soon develop
Resultant inflammatory response damages airways and results in progressive bronchiectasis, airflow limitation and eventually respiratory failure
Neonates
- Failure to thrive
- Meconium ileus
- Rectal prolapse
Respiratory
- Cough, thick mucus, wheeze, recurrent infections
- Bronchiectais and airflow limitation
- Sinusitis
- Nasal polyps
- Spontaneous pneumothorax
- Haemoptysis and SOB
Alimentary
- Thick secretions
- Reduced pancreatic enzymes due to mucus blocking pancreatic duct
- Pancreatic insufficiency (DM, steatorrhoea)
- Distal intestinal obstruction syndrome resulting in reduced GI motility
- Reduced bicarbonate
- Maldigestion and malabsorption thus poor nutrition
- Cholesterol gallstones and cirrhosis
- Increased incidence of peptic ulcers and malignancy
Other
- Males infertile due to atrophy of vas deferens and epididymis
- Females able to conceive but often develop secondary amenorrhoea as disease progresses
- Salty sweat
- Clubbing
- Osteoporosis
127
How is CF diagnosed?
```
Clinical and FHx
One or more of these
- Sweat test - high Na and Cl > 60mmol/L
- Absent vas deferens and epididymis
- GI and nutritional disorders
Genetic screening for known CF mutations
Faecal elastase test - excludes exocrine pancreas disease - low/no levels of elastase
Lots of microbiology - P aerginosa, Myocbacterium abscessus, Enterobacter spp, Kelbsiella, Prevotella spp
```
128
How is CF treated?
Multi-disciplinary team
Lung function and BMI recorded at every appointment
Education to improve QoL and good nutrition and prompt treatment of exacerbations
Stop smoking
Prophylaxis antibiotics
Pseudomonal and flu vaccine
MRSA present - treat with rifampicin and fucidin
Regular chest physio - postrual drainage, forced expiratory techniques
B2 agonists and inhaled corticosteroids - symptomatic relief
Mucolytics - dornase alfa or inhaled DNAse to clear mucus
Pancreatic enzyme replacement
Fat soluble vitamin supplements
Screening and osteoporosis treatment
Amiloride inhibits Na transport and thus less thick mucus
Bilateral lung transplant - when on maximal therapy and fully compliant psychologically well
129
What is idiopathic pulmonary fibrosis?
Type of interstitial lung disease - distinct cellular infiltrates and extracellular matrix deposition of lung distal to terminal bronchiole
Commonest cause of ILD
Most common of idiopathic pulmonary pneumonias
Patchy fibrosis of interstitium and minimal or absent inflammation, acute fibroblastic proliferation and collagen deposition
130
How common is IPF?
Unknown aetiology 20% give Hx of occupational exposure to metals and wood dusts
Mean onset 60s and presentation very uncommon under age 50
Males 2x as likely to be affected
131
What can increase your risk of getting IPF?
Smoking
Infectious agents - CMV, Hep C, EBV
Occupational dust exposure (metals, woods)
Drugs - methotrexate, imipramine (anti-depressant)
Chronic GORD
Genetic predisposition
132
What is the pathology of IPF?
Pathogenesis unknown
Repetitive injury to alveolar epithelium caused by currently unidentified envirnomental stimuli leads to activation of several pathways responsible for repair of damaged tissue
Wound healing mechanisms become uncontrolled, leading to overproduction of fibroblasts and deposition of increase extracellular matrix in interstitium and little inflammation
Structural integrity of lung parenchyma therefore disrupted - loss of elasticity and ability to perform gas exchange impaired - progressive respiratory failure
133
How does IPF present?
Pattern of lung disease described as usual interstitial pneumonitis that is patchy with sub-pleural regions of lower lobes predominantly affected
Variable interstitial inflammatory infiltrate in affected areas of lung with collapse of lung architecture and development of mystically dilated spaces within fibrotic areas
Areas of immature tissue and fibroblastic foci in less severely affected areas
Dry cough with/without sputum
Exertional dyspnoea
Malaise
Weight loss
Arthralgia
Cyanosis
Finger clubbing
Fine bi-basal end-inspiratory crackles
Step-wise deterioration due to pneumothorax, PE or intercurrent infection
Acute exacerbations with no identifiable cause and are associated with increased mortality
134
What is a possible differential of IPF?
```
COPD
Asthma
Bronchiectasis
Congestive HF
Atypical pneumonia
Lung cancer
Asbestosis
Hypersensitivity pneumonitis
```
135
How is IPF diagnosed?
Aim to confirm presence of pulmonary fibrosis and exclude identifiable causes
Bloods
- ABG - low PaO2, if severe then high PaCO2
- Raised CRP
- Raised immunoglobulins
- Check antinuclear antibodies and rheumatoid factor to exclude autoimmune rheumatic disease
CXR- small lung volume with increase reticular shadowing at bases
High resolution CT
- More sensitive than CXR
- Confident diagnosis if any of these seen - basal distribution, subpleural reticulation, traction bronchiectais, honeycombing
Spirometry/respiratory function test - restrictive pattern
Lung biopsy may be required
136
How is IPF treated?
Median survival 2-5 years
Serial lung function testing to monitor disease progression
Best supportive care
- Oxygen ambulatory
- Pulmonary rehabilitation
- Palliative care - opiates
- Treat GORD as contributes to alveolar epithelial drainage
- Treat cough
- Pirfenidone antifibrotic agent that can slow rate of FVC decline
- Lung transplent
- Do not give high dose steroids unless diagnosis in doubt
137
What is a pleural effusion?
Excessive accumulation of fluid in pleural space
138
How common is pleural effusion?
Seen in adults and less commonly in children
Recurrent pleural effusions seen in malignant mesothelioma
Pleural effusions are transudates/exudates
139
What can increase your risk of pleural effusion?
Previous lung damage
| Asbestos exposure
140
What is transudate?
Less protein (transparent)
Pleural fluid protein less than 30g/L as vessels normal so only fluid able to leak out
Occurs when balance of hydorstatic forces in chest favour accumulation of pleural fluid ie increased pressure due to backing up of blood in left sided congestive heart failure
Due to high venous pressure - HF, constrictive pericarditis, fluid overload
Hypoproteinaemia - cirrhosis, hypoalbuminaemia, nephrotic syndrome
Peritoneal dialysis
Hypothyroidism
141
What is exudate?
Exudes proteins
Pleural fluid protein more than 30g/L since endothelial cells of vessel further apart so fluid and protein can get out
Increased permeability and thus leakiness of pleural space and/or capillaries usually as a result of inflammation, infection or malignancy
Pneumonia, malignancy, TB, pulmonary infarction, lymphoma, mesothelioma, asbestos exposure, myocardial infarction
142
What may effusions also consist of? What is the result of an effusion?
More rarely consist of blood (haemothorax), pus (emphysema), lymph fluid (chylothorax)
Build up of fluid results in pressure increase that places pressure on lungs resulting in breathing difficulties
143
How does pleural effusion present?
Asymptomatic
SOB particularly on exertion
Pleuritic chest pain
Cough
Weight loss (malignancy)
Chest expansion reduced on side of effusion
In large effusion - trachea may be deviated away from effusion
Associated lung collapse - trachea deviates towards lesion
Stony dull percussion notes on affected side
Diminished breath sounds on affected side
Decreased tactile vocal fremitus
Loss of vocal resonance
144
How is pleural effusion diagnosed?
CXR
- Detected when 300ml or more fluid present
- Small effusion reduces costophrenic angles
- Larger ones water-dense shadows with concave upper borders
- Completely flat horizontal upper border implies also pneumothorax
USS
- Useful in identifying presence of pleural fluid in guiding diagnostic or therapeutic aspiration
Diagnostic aspiration
- Thoracocentesis or pleural tap
- Needle inserted under anaesthesia
- Appearance of fluid noted - purulent in empyema, tubid in infection, milky in chylothorax
- Sample sent for pH, cytology, and microbiology if infection suspected
If aspiration inconclusive then considered parietal pleural biopsy
145
How is pleural effusion treated?
Depends on underlying cause
Exudates drained in symptomatic
Transudates managed by treatment of underlying cause
Malignant effusions usually reaccumulate after drainage
Pleurodesis - injection causing adhesion of visceral and parietal pleural to help prevent reaccumulation of effusion
Surgery if persistent collections and increasing pleural thickness
146
What is a pneumothorax?
Air in pleural space
| Leads to partial/complete collapse of lung
147
How common is a pneumothorax?
Occurs spontaneously or secondary to chest trauma
Spontaneous pneumothorax most common in young males
Much more common on men
Often patients tall and thin
Both lungs affected with equal frequency
148
What causes a pneumothorax?
Rupture of pleural bleb/sub-pleural bulla
In patients over 40 underlying COPD
Other/rarer causes
- Bronchial asthma
- Carcinoma
- Breakdown of lung abscess leading to bronchopulmonary fistula
- Severe pulmonary fibrosis with cyst formation
- TB
- Pneumonia
- CF
- Trauma (penetrating or rib fracture)
- Iatrogenic eg pacemakers or central lines
149
What can increase your risk of pneumothorax?
Male
Smoking increases risk
Age - pneumothorax due to pleural bleb rupture most likely to occur between 20-40, especially if person very tall and underweight
150
What is the pathology of pneumothorax?
Normally pressure in pleural space negative but lost once communication with atmospheric pressure ie breath of pleura, elastic recoil of lung then causes it to partially deflate
Communication between airways and pleural space remains open then bronchopleural fistula results
Once communication between lung and pleural space closed, air will be reabsorbed slowly - 50% collapse will take around 40 days to reabsorb completely once air leak closed
3rd patients have recurrence
151
What is a tension pneumothorax?
Considered when pneumothorax leads to significant impairment of respiration or blood circulation
Tends to occur in ventilation, resuscitation, trauma or in patients with lung disease
Common findings - tachycardia, tachypnoea, low O2, low BP, trachea deviated away from affected side
152
How does pneumothorax present?
May be no symptoms in those fit and young with small pneumothorax
Sudden onest SOB and/or unilateral pleuritic chest pain
Pneumothorax enlarges patient becomes more breathless and may develop pallor and tachycardia
Patients with asthma/COPD may present with sudden deterioration
Mechanically ventilated patients may present with hypoxia or an increase in ventilation pressures
Reduced expansion, hyper-resonance to percussion and diminished breath sounds of affected lungs
153
What is a possible differential of pneumothorax?
Pleural effusion
Chest pain
PE
154
How is pneumothorax diagnosed?
CXR
- Do not request in tension pneumothorax wastes time
- Look for area devoid of lung markings, peripheral to edge of collapsed lung
ABGs
- In dyspnoeic patients check for hypoxia
155
How is pneumothorax treated?
Pneumothorax due to trauma, haemothorax, or mechanical ventilation requires chest drain
For tension pneumothorax do needle aspiration then chest drain
Needle aspiration to remove excess air
Observation
Oxygen for hypoxia
Surgery for persistent pneumothorax
Smoking cessation reduces recurrence rate
156
What is pulmonary hypertension?
Lung circulation offers low resistance to flow compared to systemic circulation
Normal mean pulmonary artery pressure 14 +/- 3mmHg with upper limit of normal 20mmHg
Pulmonary hypertension mPAP of > 25mmHg as measured at right heart catheterisation and secondary to right ventricular failure
157
What can cause pulmonary hypertension?
```
Occurs due to an increase in pulmonary vascular resistance or an increase in pulmonary blood flow
Pulmonary vascular disorders
- PE
- Primary pulmonary hypertension
- Veno-occlusive disease
Disease of lung and parenchyma
- COPD
- Chronic lung disorders
MSK - kyphoscoliosis, poliomyelitis, MG
Disturbance of respiratory drive - obstructive sleep apnoea, morbid obesity, cerebravascular disease
Cardiac
- Mitral stenosis
- LV failure
- LA myxoma
- Congenital heart disease
Other - appetite suppression drugs, type 1 glycogen storage diseases, lipid storage disease, rheumatic autoimmune disease, hepatic mass, sickle cell disease, familial, idiopathic
```
158
What is the pathology of pulmonary hypertension?
Hypoxic vascoconstriction, inflammation, cell proliferation resulting in narrower vessels and increased right ventricular pressure caused by pulmonary hypertension
Leads to damage of pulmonary endothelium resulting in release of vasoconstrictors such as endothelin which in turn increases pulmonary vascular resistance meaning RV must pump harder causing RV hypertrophy
Increased platelet and leukocyte adhesion, elevated serotonin and other factors cause further vasoconstriction and remodelling further increasing PVR
With progressive pulmonary hypertension develops right ventricular hypertrophy, dilatation and eventually failure resulting in death
159
How does pulmonary hypertension present?
Exertional SOB, lethargy, and fatigue initial features due to an inability to increase CO with exercise
Ankle swelling
Chest pain
Syncope
RV failure develops - oedema and abdominal pain from hepatic congestion
Loud pulmonary second sound
R parasternal heave caused by RV hypertrophy
In advanced disease features of RHF
- Elevated JVP
- Prominent V wave if tricuspid regurgitation
- Hepatomegaly
- Pulsatile liver
- Peripheral oedema
- Ascites
- Pleural effusion
160
What is a possible differential of pulmonary hypertension?
```
Cor pulmonale
Cardiomyopathies
Primary RV HF
Congestive cardiac failure
Portal hypertension
```
161
How is pulmonary hypertension diagnosed?
CXR
- Enlarged proximal pulmonary arteries which taper distally
- Enlarged heart
- May also reveal cause of pulmonary hypertension eg emphysema or calcified mitral valve
ECG
- RV hypertrophy and P pulmonale
ECHO
- RV dilatation and/or hypertophy
- Can show cause of pulmonary hypertension
LFTs to detect portal hypertension
Autoimmune screening
162
How is pulmonary hypertension treated?
Treat underlying cause
Oxygen
Warfarin - due to intrapulmonary thrombosis
Diuretics for oedema
Oral CCBs as pulmonary vasodilators
Oral endothelin receptor antagonist eg bosenten
Phosphodiesterase-5 inhibitors
Prostanoid analogues
Consider heart-lung transplant in young patients
163
What is sarcoidosis?
Type of ILD - distinct cellular infiltrates and extracellular matrix deposition in lung distal to terminal bronchiole
Multi-system granulomatous disorder of unknown cause
Affects any organ system, but commonly involves mediastinal lymph nodes and lung
Typically presents with bilateral hilar lymphadenopathy, pulmonary infiltration and skin or eye lesions
164
How common is sarcoidosis?
Usually affects adults aged 20-40
More common in women
Prevalence highest in Northern Europe
African-Caribbean's are affected more frequently and more severely than Caucasian's - particularly extra-thoracic disease
Only detected on routine x-ray
First degree relatives have increased risk of developing sarcoidosis
165
What do granulomas in sarcoidosis consist of?
Focal accumulations of epitheliod cells, macrophages and lymphocytes mainly T cells
166
How does sarcoidosis present?
20-40% discovered incidentally after routine CXR
Can affect any organ but has predilction to lung
Erythema nodusum with/without polyarthralgia
Constitutional symptoms - fever, weight loss, fatigue
Respiratory symptoms - 90% have abnormal CXRs with bilateral hilar lymphadenopathy with/without pulmonary infiltrates/fibrosis, dry cough, progressive SOB, reduced exercise tolerance, chest pain
Other symptoms - lymphadenopathy, hepatomegaly, deranged LFTs, splenomegaly, conjunctivitis, glaucoma, anterior uveitits, hypercalciuria, enlargement of lacrimal and parotid glands, Bell's palsy, facial numbness, dysphasia, visual field defects, lupus pernio, renal stones, cardiac arrhythmias, heart block
167
What is a possible differential of sarcoidosis?
```
Rheumatoid arthritis
Lymphoma
Metastatic malignancy
TB
Lung cancer
SLE
Idiopathic pulmonary fibrosis
Multiple myeloma
```
168
How is sarcoidosis diagnosed?
Bloods
- Raised ESR
- Lymphopenia
- Raised LFTs, Ca, immunoglobulins
- Serum ACE
- 24 hour urinary calcium if blood serum normal
CXR for staging
Bronchoscopy
ECG for arrhythmias of BBB
Lung function tests may show reduced lung volumes, impaired gas transfer, and restrictive ventilatory defect
Tissue biopsy - diagnostic, shows non-caseating granulomata
Bronchoalveolar lavage - increased lymphocytes in active disease, increased neutrophils if pulmonary fibrosis present
169
How is sarcoidosis treated?
Worse outcomes in patients with Afro-Caribbean and Asian descent and those with extra-thoracic disease
Patients with bilateral hilar lymphadenopathy don't need treatment as most will recover spontaneously
Don't treat symptomatic patients stage 1
Don't treat asymptomatic patients stage 2/3
Acute - bed rest and NSAIDs
Corticosteroids
- Prednisolone orally then gradually reduce dose
- In severe illness IV methylprednisolone
- If steroid resistant then methotrexate by lose monitoring required
Transplantation in severe cases
Treat extra-organ complications
170
What is Goodpasture's syndrome?
Co-existence of acute glomerulonephritis and pulmonary alveolar haemorrhage and presence of circulating antibodies directed against an intrinsic antigen basement membrane of both kidney and lung
171
How common is Goodpasture's syndrome?
Rare in children and usually occurs in individuals over 16 years
In adults more common in men
172
What is the pathology of Goodpasture's syndrome?
Specific autoimmune disease caused by type II antigen-antibody reaction leading to diffuse pulmonary haemorrhage and glomerulonephritis
Circulating antiglomerular basement membrane antibodies
173
How does Goodpasture's present?
Upper respiratory tract infection eg sneezing, nasal discharge, nasal congestion, runny nose, fever
Cough
Intermittent haemoptysis
Tiredness
Anaemia - may result from persistent intrapulmonary bleeding
Acute glomerulonephritis
174
What is a possible differential of Goodpasture's?
Idiopathic pulmonary haemosiderosis
SLE
Rheumatoid arthritis
175
How is Goodpasture's diagnosed?
Presence of anti-basement membrane antibodies in blood
CXR - transient patchy shadows/pulmonary infiltrates due to pulmonary haemorrhage often in lower zones
Kidney biopsy showing crescentic glomerulonephritis
176
How is Goodpasture's treated?
```
Some may spontaneously improve
Others precede on renal failure
Treat shock
Vigorous immunosuppressive treatment
- Corticosteroids eg prednisolone
- Plasmapheresis
```
177
How is sarcoidosis staged?
Stage 0 normal
Stage 1 bilateral hilar lymphadenopathy
Stage 2 pulmonary infiltrates with BHL
Stage 3 pulmonary infiltrates without BHL
Stage 4 progressive pulmonary fibrosis, bulla formation and bronchiectasis
178
What is hypersensitivity pneumonitis?
Type of interstitial lung disease - distinct extracellular infiltrates and extracellular matrix deposition in lung distal to terminal bronchiole
179
What are interstitial lung diseases?
Group of lung diseases affecting the lung interstitium
180
How common is hypersensitivity pneumonitis?
Disease of adults
Caused by allergic reaction affecting small airways and alveoli in response to an inhaled antigen or occasionally following ingestion of causative drug
Acute, subacute and chronic forms
181
What can cause hypersensitivity pneumonitis?
Acute and subacute cause pneumonitis which can be recurrent
Chronic - fibrosis, emphysema and permanent lung damage
One of most common causes - farmer's lung
Associated with many jobs and hobbies
- Farmer's lung due to exposure of mouldy hay
- Bird/pigeon fancier's lung exposure to avian proteins in droppings
- Cheese workers lung mouldy cheese
- Malt-workers lung mouldy malt
- Humidifier fever contaminated humidifying systems in air conditioners or humidifier in factories
182
What can increase your risk of getting hypersensitivity pneumonitits?
Pre-existing lung disease
Specific occupations including farmers, cattle workers, ventilation system workers, vets and those jobs that work with chemicals
Bird keeping
Regular use of hot tubs
183
What is the pathology of hypersensitivity pneumonitits?
Diffuse, granulomatoud inflammation of lung parenchyma and airways in people who have been sensitised by repeated inhalation of organic antigens in dust
Allergic response involves cellular immunity and deposition of immune complexes (Type III hypersensitivity) resulting in inflammation through activation of complement via classical pathway
Some of inhaled antigen may lead to inflammation by directly activating alternative complement pathway
Attract and activate alveolar and interstitial macrophages so continued antigenic exposure results in progressive development of pulmonary fibrorsis
In acute phase - alveoli infiltrated with acute inflammatory cells
Chronic exposure - granuloma formation and obliterative bronchiolitis occur
184
What is the pathology of Farmer's lung?
Fugus in mouldy hay inhaled
Already sensitised to organism
Acute SOB and cough few hours after inhalation of antigen
Bronchiolitis one of earliest features
Chronic inflammatory cells seen in interstitium together with non-caveating granulomas
Inflammatory process may resolve on withdrawal of antigen but if chronic exposure then fibrosis
185
What is the acute response in hypersensitivity pneumonitis?
```
4-6 hours post-exposure
Fever, rigors, myalgia
Dry cough
SOB
Crackles
Chest-tightness
May be mistakenly diagnosed with chest infection
Symptoms related to level of exposure
Resoluton 24-48 hrs following removal of antigen
```
186
What is the subacute response in hypersensitivity pneumonitis?
Occurs with intermittent or lower-level exposure
Hx or repeated acute attacks
Signs same as acute, symptoms less severe and more gradual onset
Present as recurrent pneumonia
Improvement seen in weeks to months following removal from exposure
187
What is the chronic response in hypersensitivity pneumonitis?
Usually no Hx of preceding acute symptoms
If source of antigen removed only partial improvement
Cyanosis and clubbing may develop
Weight loss
Increasing SOB
T1 respiratory failure (low PaO2, normal/low paCO2)
188
What is a possible differential for hypersensitivity pneumonitis?
```
Infection
Connective tissue disorders causing interstital lung disease
Pulmonary fibrosis
Asthma
Drug induces interstitial lung disease
```
189
How is hypersensitivity pneumonitits diagnosed?
CXR
- Fibrotic shadow in upper zone of lung
- Diffuse small nodules and increased reticular shadowing may be present but not specific
FBC
- Raised WCC
- Increased ESR (inflammatory cell markers)
Lung function test
- Reversible restrictive defect
- Reduced gas transfer during acute attacks
Bronchoalveolar lavage
- Analysis of lymphocyte count and CD4/8 ratio
190
How is hypersensitivity pneumonitis treated?
```
Acute
- Remove antigen
- Give O2 (35-60%)
- Oral prednisolone followed by reducing dose
Chronic
- Avoid exposure to allergen
- Long term steroids can often achieve CXR and physiological improvement
- Corticosteroids
```
191
What is mesothelioma?
Malignant mesothelioma strongly associated with asbestos exposure
Tumour of mesothelial cells of pleura
Other sites include mesothelial cells of peritoneum, pericardium and testes
192
How common is mesothelioma?
More common in men
Often presents between 40-70
Exposure to asbestos well established cause
Latent period between exposure and development of tumour may be up to 45 years
193
What is the pathology of mesothelioma?
High grade malignancy of pleura that spreads around pleural surfaces
Can also start in pericardial space, peritoneal space and paratesticular space
Begins as nodules in pleura that extend as confluent sheet to surround lung and extend into fissures
Chest wall often invaded, with infiltration of intercostal nerves - severe intractable pain
Lymphatics may be invaded, give hilar node metastases
194
How does mesothelioma present?
```
Chest pain
SOB
Weight loss
Finger clubbing
Recurrent pleural effusions
Signs of metastases - lymphadenopathy, hepatomegaly, bone pain/tenderness, abdominal pain/obstruction
```
195
How is mesothelioma diagnosed?
```
CXR and CT
- Unilateral pleural effusion
- Pleural thickening
Bloody/straw coloured pleural fluid
Pleural biopsy
```
196
How is mesothelioma treated?
Surgery for extremely localised mesothelioma
Generally, resistant to surgery, chemotherapy and radiotherapy
Average time from diagnosis to death around 8 months
Refer all mesothelioma deaths to HM coroner
Poor prognosis
197
What is an occupational lung disorder?
Response to inhaling something at work
| Can be fumes, dust, gas or vapour causing many different conditions
198
How are occupational lung disorders classified?
Acute bronchitis and oedema from irritants such as SO2, Cl, ammonia or oxides of nitrogen
Pulmonary fibrosis from inhalation of inorganic dust - coal, silica, asbestos, iron and tin
Occupational asthma
Hypersensitivity pneumonitis
Bronchial carcinoma due to asbestos, polycyclic hydrocarbons and radon in mines
199
What is coal worker's pneumoconiosis?
Accumulation of dust in lungs and reaction of tissue to its presence
Common in countries with coal mines
Inhalation of dust particles over 15-20 years
Particles ingested by alveolar macrophages in small airways and alveoli which then die releasing enzymes and causing fibrosis
200
What is silicosis?
Uncommon but seen in stonemasons, sand-blasters, pottery and ceramic workers and foundry workers involved in fettling
Inhalation of silica particles which is very fibrogenic
Silica particularly toxic to alveolar macrophages and readily initiates fibrogenesis
CXR appearance shows diffuse nodular pattern in upper and mid-zone and thin streaks of calcification of hilar nodes
Spirometry shows restrictive ventilatory defect
Progressive SOB and increased incidence of TB
Manage by avoiding exposure to silica and claim compensation
201
What is asbestosis?
Type of ILD distinct cellular infiltrates and extracellular matrix deposition in lung distal to terminal bronchiole
Significant time lag between exposure and development of disease
Risk of primary lung cancers increased in those exposed
Fibrosis to lungs caused by asbestos dust, associated with fibrosis of parietal and visceral layers of pleura
Progressive disease charaterised by breathlessness and progressive dyspnoea and accompanied by finger clubbing and bilateral basal end-inspiratory crackles
Pleural plaques and increases risk of mesothelioma and bronchial adenocarcinoma
Only symptomatic management corticosteroids
202
What is byssinosis?
Worldwide but declining particularly in areas where number of people working in cotton mills falling
Symptoms occur on first day back at work after break with improvement as week progresses
Chest tightness, cough, SOB occurs within first hour in dusty areas of cotton mill
Those with asthma affected badly
No changes seen on CXR and aetiology unknown
203
What is berylliosis?
Beryllium widely use in aerospace industry, atomic reactors and many electrical devices
When beryllium inhaled can cause systemic illness with clinical picture similar to sarcoidosis
Progressive SOB with pulmonary fibrosis
Rare
204
What is pulmonary vasculitis?
Inflammation and destruction of pulmonary vasculature with subsequent tissue necrosis
205
What are the different types of pulmonary vasculitis?
Systemic autoimmune vasculitits - small vessel (ANCA associated and immune-complex mediated)
Secondary causes - infection, drug reaction, connective tissue disease (SLE, mixed and antiphospholipid syndrome), malignancy
206
How does pulmonary vasculitis present?
```
Diffuse alveolar haemorrhage
Pulmonary nodules
Cavities
Recent onset asthma
Upper airway disease
Extrapulmonary manifestation
- Glomerulonephritis
- Fever
- Weakness
- Weight loss
- Mononeuritis multiplex
```
207
What is a possible differential diagnosis of pulmonary vasculitis?
```
Infection
Malignancy
Connective tissue disease
Drug toxicity
Venous thromboembolic disease
```
208
How is pulmonary vasculitis diagnosed?
```
Lab tests - ANCA
Evaluation for connective tissue disease - antinuclear antibodies, rheumatoid factor, disease specific antibodies
CXR/CT
Bronchoscopy
Pulmonary function tests
Tissue biopsy
```
209
How is pulmonary vasculitits treated?
Induction - immunosuppression with corticosteroids and cytotoxic immunosuppressive agents
Maintenance
210
What is Wegner's granulomatous?
Granulomatous disease of unknown aetiology
Type of ANCA-associated vasculitis
Multisystem disorder of unknown origin characterised by necrotising granulomatous inflammation and vasculitits of small and medium vessels
211
What is the pathology of Wegner's granulomatosis?
ANCA
Inflammation of blood vessels with granulomas
Autoantibodies made to neutrophil proteins
As neutrophil rolls along blood vessels before it migrates into tissues autoantibodies bind to it and activate neutrophils inappropriately
Results in recruitment of more neutrophils and more activated neutrophils when there is no infection
Results in production of reactive oxygen species and neutrophil degranulation
Leading to generation of microabscesses, recruitment of monocytes and macrophages and lymphocytes to make granulomas
Results in devastating inflammation affecting many organs including lung and kidney
212
How does Wegner's granulomatosis present?
Lesions involve upper respiratory tract, lungs and kidneys
Starts with severe rhinorrhoea and subsequent nasal mucosal ulceration
Cough, pleuritis pain, haemoptysis
Renal disease causes rapidly progressive glomerulonephritis with crescent formation, proteinuria, haematuria
Skin purpura or nodules, peripheral neuropathy, arthritis/arthralgia
213
What is a possible differential for Wegner's granulomatosis?
Churg-Strauss syndrome
214
How is Wegner's granulomatosis diagnosed?
Bloods - c-ANCA positive, elevated PR3 antibodies, raised ESR/CRP
CXR - nodular masses or pneumonic infilatrates with cavitation clear migratory pattern
CT - diffuse alveolar haemorrhage
Urinalysis to check for proteinuria and haematuria - if present then consider renal biopsy
215
How is Wegner's granulomatosis treated?
Depends on disease extent
Severe disease treated with corticosteroids and cyclophosphamide or rituximab to induce remission
Azathioprine and methotrexate usually used as maintenance
216
What is obstructive sleep apnoea?
When breathing stops during sleep
217
What can increase your risk of obstructive sleep apnoea?
```
Obesity
Large neck
Increasing age
FHx
Smoking and drinking alcohol
Large tonsils
Sleeping on back
```
218
What occurs in obstructive sleep apnoea?
Relaxation of pharynx during sleep resulting in occlusion
219
How does obstructive sleep apnoea present?
```
At night
- Breathing stopping and starting
- Gasping, snorting or chocking noises
- Waking up a lot
- Loud snoring
During day
- Feel very tired
- Hard to concentrate
- Mood swings
- Wake up with headache
```
220
How is obstructive sleep apnoea diagnosed?
Referral to sleep clinic
Devices to check breathing and HR whilst asleep
How severe condition is determined by AHI score
221
How is obstructive sleep apnoea treated?
```
CPAP machine
Mandibular advancement devices
Surgery to help breathing
Weight loss if overweight
Sleep on side
Smoking cessation
Don't drink too much alcohol especially shortly before sleep
Don't take sleeping pills
Tell DVLA
```
222
What are the possible complications of obstructive sleep apnoea?
```
Hypertension
Stroke
Depression or changes in mood
Higher chance of serious accident caused by tiredness
Difficulty concentrating at work/school
```
223
What is type 1 respiratory failure?
pO2 low
pCO2 low/normal
Type 1 = 1 change
Eg PE
224
What is type 2 respiratory failure?
pO2 low
pCO2 high
Type 2 = 2 changes
Eg hypoventilation
225
What can cause respiratory failure?
Impaired ventilation
- Neural problems due to narcotics, encephalitis, cerebral space occupying lesion, MND
- Mechanical problems - airway obstruction, trauma, muscle disease, pleural effusion
- Impaired gas exchange defects, if severe eg emphysema or diffuse pulmonary fibrosis
226
What is obstructive respiratory disease?
FEV1/FVC < 0.7
FEV1 < FVC
Asthma - variable airflow obstruction, reversible
COPD - relatively fixed airflow obstruction, can be mixture of both
Bronchietasis
227
What is restrictive respiratory disease?
FEV1/FVC > 0.7
FVC and FEV1 < 80% predicted
Due to resitriction, lung volumes small and most breath out in first second
ILD - fibrosing alveolitis, sarcoidosis
228
What is transfer co-efficient?
Measure of ability of O2 to diffuse across alveolar membrane
Calculated by inspiring CO, holding breath for 10 seconds at TLC then gas transferred measured
Low in - severe emphysema, fibrosing alveolitis, anaemia, pulmonary hypertension, idiopathic pulmonary fibrosis,COPD
High in - pulmonary haemorrhage
229
What are the signs of hypercapnia?
```
Bounding pulse
Flapping tremor
Confusion
Drowsiness
Reduced consiousness
```
230
Name a SABA
Salbutamol
| Terbutaline
231
Name a LABA
Salmeterol
| Formoterol
232
How do beta2-agonists work?
Beta-2 selective
Only work in lungs (B1 = heart, B3 = adipose tissue)
High doses not selective and will act on other receptors
B2 agonist binds to B2 receptor coupled with Gs protein resulting in adenyl cyclase converting ATP into cyclic AMP and increasing cyclic AMP leads to bronchodilation
Beta-agonists inhibit mast cell activity reducing inflammatory response
At high concentrations a tolerance may develop due to B2-receptor desensitisation
233
What is the difference between LABA and SABA?
LABA lasts for 12 hours
SABA lasts for 4
LABA longer acting as more lipophilic so can remain in tissue for longer
234
Name a short acting muscarinic antagonist
Ipratropium
235
Name a long acting muscarinic antagonist
Tiotropium
236
How do muscarinic antagonists work?
Act on airway M3 receptors
Normally ACh (parasympathetic) binds to M3 receptor bound to Gq protein resulting in phospholipase C converting phosphate to DAG resulting in protein kinase C production that results in smooth muscle contraction
Muscarinic antagonists prevent ACh from binding since they bind to M3 receptor blocking ACh action
237
Name an example of a methylxanthine
Theophylline
| Aminophylline
238
What are methylxanthines?
Phosphodiesterase inhibitors preventing conversion of cyclic-AMP to 5-AMP resulting in build up of cyclic AMP and increased smooth muscle relaxation
239
Name an example of a glucocorticoid?
Prednisolone
Beclomatatsone
Budesonide
240
How do glucocorticoids work?
Interfere with gene transcription
Glucocorticoid receptor found on promoter region of DNA has zinc fingers that anchor receptor to DNA and recognise discrete sequences
Either + glucocorticoid response element that increases transcription or - GRE decreasing transcription
- GRE results in cytokine supression reducing inflammation and reducing symptoms
+ GRE results in increased lipcortin which inhibits PLA2 meaning there is a decrease in arachidonic acid and decrease in prostaglandinds and leukotrienes resulting in reduced inflammation and reducing symptoms
241
What are the side effects of glucocorticoids?
Susceptibility to infection due to cytokine supression
| Metabolic such as osteoporosis and muscle wasting
242
What other agents have bronchodilator activity?
Leulotriene receptor antagonist eg montelukast
| Oral corticosteroid needed for those not controlled on inhaled
243
What steroid sparing agents are available for asthma treatment?
Methotrexate
Ciclosporin
IV immunoglobulin
Anti-IgE monoclonal antibody
