Seminar 5 - Smoking Associated Lung Disease Flashcards
What is the difference between type 1 and 2 respiratory failure
Type 1 has just hypoxia with low or normal CO2
Type 2 has hypoxia with hypercapnia
Describe the course of subacute fibrotic lung diseases
Have a resolving, remitting, relapsing or progressive course
In which lung disease would you see increased serum ACE and Ca2
Sarcoidosis
How does CTEPH present on V/Q scan
Will have one or more segmental or larger unmatched perfusion defects
Describe the pathogenesis of Group 3 PH
Lung disease leads to hypoxia
Pulmonary vasoconstriction occurs in response to this.
This process is normally reversible but sustained hypoxia activates further mediators which leads to remodelling and increase in pulmonary vascular resistance.
As a result, the pressure in the vessels rises and you get PH
What is anthracnosis
Form of pneumoconiosis
Most innocuous coal-induced lesion
Seen to some extent in city living & smokers)
Usually doesn’t cause fibrosis but can if severe
What causes the diaphragm paralysis seen in lung cancer
Phrenic nerve invasion
What proportion of COPD patients have PH
10-30%
List the symptoms of Horner’s syndrome
Unilateral ptosis, miosis, anhidrosis and enophthalmos
How do you differentiate between obstructive and restrictive lung disease
History and examination can help but often considerable symptom overlap
Main way is via pulmonary function tests such as spirometry
What are asbestos bodies
Long, thin asbestos fibres with translucent centre and gold-brown colour
Consists of asbestos fibres coated with iron-containing proteinaceous material
How do you name benign tumours of mesenchymal cells
Suffix “-oma” is attached to the name of the cell type from which the tumor arises
e.g. lipoma
What determines the outcome of Group 1 PAH
The underlying cause, severity and available treatment options
Also a list of prognostic factors (other card)
Describe the prevalence of intrinsic lung diseases
Overall prevalence of 3-6 cases/100,000 people (US)
Idiopathic pulmonary fibrosis (IPF) prevalence in UK is 50/100,000
What is the most common cause of cor pulmonale
COPD
List examples of chest wall disorders
Severe obesity
Pleural diseases (e.g. trapped lung, scarring, large pleural effusions, chronic empyema)
Kyphoscoliosis
Neuromuscular diseases (e.g. MG, ALS, myopathy)
What can decrease mortality in COPD
Smoking cessation has been shown to decrease mortality
Which pneumoconiosis is not associated with an increased risk of TB or cancer development?
Coal workers’ pneumoconiosis
(when considering disease on its own – non-smokers)
Indoor smoky coal can increase risk but rare in western world
Which HLA genotypes are associated with sarcoidosis
HLA-A1 and HLA-B8
In which lung disease would you see
ground-glass opacities on CXR
Pulmonary fibrosis
Describe the prevalence of sarcoidosis
in US: 10-40/100,000people.
Prevalenceof this disease is hard to determine as hard to diagnose
10x more common in African Americans than Caucasians
How does Respiratory bronchiolitis-associated interstitial lung disease present
Patients will have significant pulmonary symptoms, abnormal lung function and imaging abnormalities
Term reserved for these patients
What are the 2 main components of every tumour
Neoplastic cells that constitute the tumor parenchyma
Reactive stroma made up of connective tissue, blood vessels and cells of the adaptive and innate immune system
Describe V/Q mismatch
It is the most common cause of hypoxemia
The levels ventilation and blood flow do not match - not sufficient gas exchange
Caused by reduced ventilation from airway, interstitial lung disease or reduced perfusion in PE (blood cannot reach ventilated alveoli)
What environmental factors increase you risk of COPD
Long term pollution exposure Cigarettes - biggest cause Airway hyper-reactivity IV drug use - pulmonary vascular damage Immunodeficiency e.g. HIV Vasculitis - HVUS Connective tissue disorders e.g. Marfans, Ehler's Danlos
What is the typical mechanism of death in COPD
Fatal due to heart failure or of respiratory failure due to superimposed infection
What signs may be found on examination of a patient with CTEPH
may hear reduced or fixed splitting of the second heart sound, louder pulmonary valve closure or feel a right ventricular heave.
Which diseases affecting the lung parenchyma can cause cor pulmonale
COPD Bronchiectasis Pulmonary Fibrosis Severe, chronic asthma Lung resection
Describe the pathogenesis of atopic asthma
Following exposure to allergen, Th2 cells producecytokines (interleukins 5, 4 and 13) which activate leukocytes such as eosinophils and stimulate production of IgE
The T cells and epithelial cells recruit more eosinophils, perpetuating this reaction
The IgE produced by B cells binds to FC receptors on mast cells
Repeated exposure to the allergen causes mast cells to degranulate
The early phase hypersentivity reaction kicks in followed by the late phase
How can infections contribute to asthma
Children with LRTI have a 10-30 fold increased risk of developing persistent or severe asthma
Infections also exacerbate asthma
How does chromatin appear in the nuclei of malignant cells
Coarsely clumped and distributed along the nuclear membrane
More darkly stained than normal (hyperchromatic)
Which of the components of COPD causes reversible damage
Bronchoconstriction due to inflammation accounts for some reversibility
Airflow obstruction in emphysema is often irreversible
Which lung cancers could be classed as T4
Tumour > 7cm
OR
Involvement of the mediastinum, heart, great vessels, trachea, oesophagus, recurrent laryngeal nerve, vertebral body or carina OR
Separate tumour nodules in a different ipsilateral lobe
How does silicosis present on CXR
Fine nodularity in upper zones
Eggshell calcification (Ca surrounding zone lacking calcification)
Seen as thin sheets of calcification in lymph nodes.
In which lung disease would you see polyploid plugs of loose connective tissue called Masson bodies
Cryptogenic Organising Pneumonia
Also called Bronchiolitis obliterans organising pneumonia (BOOP)
What causes Group 2 PAH
Left sided heart disease
How do you diagnose pulmonary haemorrhage
Bloods - FBC, coagulation studies, serology
Bronchoscopy - assess bleeding site
Lung biopsy - carried out if the less invasive tests cannot find a cause
Further tests may be carried out if a specific cause is suspected
Which lung cancers could be classed as N3
Metastasis to contralateral mediastinal or hilar lymph nodes, ipsilateral or contralateral scalene, or supraclavicular lymph nodes
Why is asthma a disease of industrialized/urban environments (describe the 2 main theories)
Cities contain many allergens that can initiate a Th2 response such as airborne pollutants
Hygiene hypothesis - City life tends to limit children’s exposure to antigens which could provide a protective effect against atopy
List the subtypes of non-small cell lung cancer
Adenocarcinoma - most common
Squamous cell
Large cell undifferentiated
Others such as carcinoid
Describe the progression of Group 1 PAH
Progressive and sustained rise in pulmonary vascular pressure.
Typically caused by vasoconstriction, remodelling and thrombosis in the small pulmonary arteries and arterioles.
Can progress to right heart failure
For a coagulation disorder to lead to pulmonary haemorrhage, what else is typically needed
Often need a precipitant like infection
What are the clinical features of pulmonary haemorrhage
Classic symptoms: dyspnoea, haemoptysis and iron deficiency anaemia
Exact clinical presentation varies depending on the underlying cause (will have symptoms of that disease
Chronic bleeding may cause fever, cough, weight loss and tiredness
List the main signs of asthma
Diurnal variability
Triggers – exercise, allergens, infection, cold weather, drugs (NSAIDS)
Associated atopy (eczema, hayfever etc) - due to increased IgE levels
Blood eosinophilia > 3%
Responsive to steroids or beta-agonists
FMHx of asthma
Which people get respiratory bronchiolitis-associated interstitial lung disease
Typically current smokers with >30 pack year history in 40/50s
What types of radiation can increase risk of lung cancer
Uranium – 4x risk in non-smoking Uranium miners
Radon gas – Increased risk of exposure in underground workers and places with high soil concentration
Ionising radiation – Increased incidence in atomic bomb survivors, as well as those involved in the Chernobyl clean-up
What is chronic bronchitis
Defined clinically as the presence of a chronic productive cough for 3 months during each of 2 consecutive years with other causes of cough being excluded
Describe the epidemiology of Group 4 PH (basically CTEPH)
3-5 cases per 100,000 in the US and Europe.
Exact incidence after PE is uncertain though 75% of CTEPH patients had a previous PE.
Often underdiagnosed
No sex difference
What may you see on chest examination of a patient with COPD
Hyperinflation (barrel chest)
Wheezing – Frequently heard on forced and unforced expiration
Diffusely decreased breath sounds
Hyperresonance on percussion
Prolonged expiration
Coarse crackles beginning with inspiration in some cases
Discuss the mortality rates in COPD
Globally, it is estimated that 3.17 million deaths were caused by the disease in 2015 (that is, 5% of all deaths globally in that year
List the macroscopic features of complex coal worker’s pneumoconiosis
Causes progressive massive fibrosis
Intensely blackened scars 1cm+; usually multiple
Is is chronic bronchitis or emphysema that affects the elastic recoil of the lungs
Emphysema - reduces it
Normal in CB
Describe the prognosis of respiratory failure
Respiratory failure itself doesn’t have an exact prognosis because it is determined by the underlying cause
What is asbestos
A family of crystalline hydrated silicates
Different forms such as serpentine chrysotile form (90% of asbestos in industry) and amphiboles form (less prevalent, more pathogenic)
Associated lung disease
How does asbestosis present on CXR
Circumscribed densities
List common asthma co-morbidities
Rhinitisandrhinosinusitis Obesity Obstructive sleep apnoea GORD May overlap with COPD Mental health disorders (anxiety/depression)
How do you measure pulmonary arterial pressure
Cardiac catherisation
Describe the characteristics of usual interstitial pneumonia
Fibrosis seen on histology
Non-uniform (patchy), variegated lung injury
Alternating areas of healthy lung, interstitial inflammation, fibrosis and honeycomb change
Discuss the common mechanism of death in COPD
Airflow obstruction is associated with increased mortality, even with mild impairment
In mild to moderate COPD, majority of deaths are due to cardiovascular disease or lung cancer,
As COPD severity increases, respiratory deaths are increasingly common
How do you name a cancer if the cells are of unknown origin
Designated merely as undifferentiated malignant tumors
Only occurs in around 2% of cases
What are some of the possible carcinogens in tobacco
Polycyclic aromatic hydrocarbons
Phenol derivatives
Nitrosamines
Radioactive elements
Describe the early phase reaction of atopic asthma
Consists of:
Bronchoconstriction - triggered by direct stimulation of parasympathetic receptors through reflexes triggered by mediators produced by mast cells
Increased mucus production
Variable degrees of vasodilatation and increased vascular permeability
What are the characteristics of Desquamative interstitial pneumonia (DIP) and Respiratory bronchiolitis-associated interstitial lung disease
Large collections of macrophages in airspaces of a current or previous smoker
Called smokers macrophages
Some macrophages have lamellar bodies (contain surfactant) within phagocytic vacuoles.
Alveolar septa thickened by sparse inflammatory infiltrate of lymphocytes, plasma cells and some eosinophils
List the macroscopic features of Group 1 PAH
Hypertrophy of intima, media and adventitia of pulmonary arteries
What are the two aetiological categories of restrictive lung disease
Chest wall disorders
Chronic infiltrative and interstitial disease
Where are you most likely to find pleural plaques in asbestosis
Found on anterior and posterior-lateral aspects of parietal pleura and over diaphragm domes
Group 1 PAH is a diagnosis of exclusion - true or false
True
You must differentiate it from the other WHO groups
List some of the common medication side effects seen in the treatment of asthma
Rapid heartbeat Hoarseness Throat irritation (ICS) Oral yeast infections (ICS) Insomnia (theophylline) Gastroesophageal reflux (theophylline)
Describe the typical course of silicosis
Follows a slow & insidious course (10-30y after exposure)
However it can be accelerated (<10y) or rapid (weeks-months after intense exposure to fine dust high in silica).
Describe the structure of the pleural plaques seen in asbestosis
Well-circumscribed plaques of dense collagen
Often calcified
Don’t contain asbestos bodies but rarely occur w/o exposure to asbestos.
Describe the epidemiology of Group 2 PAH
Around 6.5 million people in Europe have heart failure
Of those with a reduced ejection fraction, 60% have this PH on presentation
Neoplasms are typically soft and fleshy
True
Connective tissue is usually scant
What proportion of patients with sleep disordered breathing have PH
In obstructive sleep apnoea it is roughly 15-20%
If other sleep-related breathing disorders are included this rises to 17-53%
Which paraneoplastic syndromes may be caused by squamous cell lung cancer
PTH/ PTHRP/ prostaglandin E production can lead to hypercalcaemia
How might diffuse alveolar haemorrhage appear on CT 2-3 days after the haemorrhage
In between chronic bleeds
Centrilobar nodules that are diffusely distributed
Repeated haemorrhage may progress to fibrosis
What causes Group 4 PH
Obstruction in the pulmonary arteries
Major cause is Chronic thromboembolic pulmonary hypertension (CTEPH
Is there a gender difference in COPD
Previously more common in men
However, more women in high income countries smoke and in low income women are at higher risk of indoor pollutants (cooking) so now equal amongst prevalence the sexes
Which parts of the lung are most commonly affected by asbestosis
Begins in lower lobes & sub-pleura
Middle and upper become affected as it progresses
How do you treat bronchiectasis
Antibiotics Mucus thinners - often nebulized Airway Clearance Devices Chest physio O2 therapy Quit smokingand avoid secondhand smoke Healthy lifestyle
List the types of granulomatous diffuse parenchymal lung disease
Sarcoidosis
Hypersensitivity pneumonitis
What is the definition of pneumoconiosis
Non-neoplastic lung reaction to inhalation of dusts encountered in the workplace; now includes chemical fumes & vapour inhalation too.
How does asbestos cause asbestosis
Inhaled fibres settle at alveolar duct bifurcations Phagocytosis by macrophages triggers cytokine release Begins process of fibrosis
In COPD, when the emphysema is mild, what is the main mechanism of airflow limitation
Bronchiolar abnormalities are most responsible for the majority of the deficit in lung function.
The drugs given to treat the heart failure in cor pulmonale can have what complications
Diuretics – hypokaleamia and arrhythmia
Ace inhibitor – angioneurotic oedema
When does CTEPH typically present
Typical age of onset is 60s.
Describe the late phase reaction of atopic asthma
Consists of the recruitment of leukocytes (eosinophils, neutrophils and more T cells)
What environmental factors can cause lung cancer
Tobacco
Asbestos
Radiation
Describe the pathogenesis of bronchiectasis
Obstruction or infection result from a defect in airway clearance
Specific causes - Primary ciliary dyskinesia and allergic bronchopulmonary aspergillosis
In COPD what are the main clinical differences that will be seen in history and examination
COPD patient will typically have:
Smoking history, older age, cough with sputum, slowly progressive exertional dyspnoea with less day-to-day variability; examination not usually abnormal until airflow limitation is severe
Describe the pathogenesis of non-eosinophilic asthma
Mechanism is poorly understood
Some patients exhibit neutrophil-predominant disease with release of cytokines fromT helper 1 cells,
Which lung cancers could be classed as M1
M1a – Separate tumour nodule in contralateral lobe OR pleural nodules OR malignant or pericardial effusion
M1b – Single extra-thoracic metastasis in a single organ
M1c – Multiple extra-thoracic metastases
Which population group is commonly affected by pulmonary haemorrhage?
Children, particularly premature or low weight infants
List the symptoms of cor pulmonale
Dyspnea on exertion Fatigue Lethargy Exertional syncope and chest pain Abdominal distension Lower extremity swelling
Which part of the lung is most commonly affected by idiopathic interstitial pneumonia
Lower zone, subpleural, and para-septal
How does interstitial lung disease typically present on spirometry
Classical restrictive functional abnormalities
Reduction in diffusion capacity, lung volume and lung compliance.
What is anaplasia
A lack of differentiation
Considered a hallmark of malignancy - they are highly anaplastic
What is the most prevalent occupational disease in the world
Silicosis
Describe the general pathogenesis behind diffuse parenchymal lung disease
Thought to begin with an acute injury to the pulmonary parenchyma
This leads to chronic interstitial inflammation
This results in -> fibroblast activation and proliferation with eventual pulmonary fibrosis + tissue destruction
Describe the pathological features of subacute phase hypersentivity pneumonitis
Interstitial pneumonitis and non-caseating granulomas
Characteristically centred on bronchioles.
Hypertrophic pulmonary osteoarthropathy is associated with what clinical sign
Finger clubbing
What is the difference between tumour giant cells and inflammatory/foreign body giant cells
The inflammatory/foreign body giant cells are derived from macrophages and contain many small, normal-appearing nuclei
The tumour giant cells have either a single huge polymorphic nucleus/two or more large hyperchromatic nuclei
What is the underlying pathology in COPD
Chronic bronchitis and emphysema
Small cell lung carcinoma is seen in non-smokers - true or false
False
99% of cases occur in smokers
Which paraneoplastic syndromes may be caused by small cell lung cancer
SIADH - leads to hyponatraemia
Ectopic ACTH production leads to cushing syndrome
How do you treat squamous cell lung cancer
Surgery, radiotherapy, chemotherapy
Research ongoing into immunotherapy and angiogenesis inhibitors
Which diseases affecting the lung vasculature can cause cor pulmonale
PE - large or recurrent Vasculitis Primary pulmonary hypertension ARDS Sickle cell disease
Why does pulmonary vasoconstriction occur in response to hypoxia
Aims to increase ventilation/perfusion matching by diverting blood away from hypoxic areas
Usually reverses when lung disease resolves - e.g. infection
However, if hypoxia is chronic it can lead to PH
How do you diagnose CTEPH
Chest radiography
Echo - used to exclude other heart diseases
V/Q scan - recommended first line if CTEPH suspected (can also exclude CTEPH)
CT or MRI
Catheter used to confirm PH
What is emphysema
Defined pathologically as an abnormal, permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis
When does non-allergic asthma present
Can present at any age
including during viral respiratory infections
In children it is more likely to resolve in adolescence
More common in adult women - especially if obese
In which lung disease would you see bilateral hilar lymphadenopathy, erythema nodosum, fatigue and weight loss
Sarcoidosis
List the pathological changes seen in the acute exudative phase of ARDS
Lungs are heavy, boggy, firm and red in colour
There is oedema in the interstitium and alveoli alongside inflammation, deposition of fibrin and diffuse alveolar damage
There are waxy hyaline membranes made from oedema fluid full of fibrin and parts of necrotic epithelial cells lining the alveoli
What is desmoplasia
Growth of fibrous or connective tissues
Parenchymal cells of tumours can stimulate the formation of abundant collagenous stroma
List the cytologic features of a malignant neoplasia
High nuclear to cytoplasmic ratio
Pleomorphisms - variation in nuclear or cell size
Hyperchromatic nuclei
Mitoses present - especially irregular or bizarre
Marked architectural disturbance and a loss of polarity
What is the most common non-cutaneous cancer worldwide
Lung cancer
List the microscopic features of Group 3 PH
Again depends on underlying lung disease
Will also have the plexiform lesions seen in other PH groups
Similar appearance to group 1 or ‘primary’ PAH
What can cause diffuse pulmonary haemorrhage
Pulmonary vasculitis’s (e.g. GPA, microscopic polyangiitis, Churg-Strauss and SLE)
Goodpasture syndrome - non-ANCA vasculitis
Can occur following a bone marrow transplantation
All-trans-retinoic acid (ATRA) syndrome
Pulmonary hemosiderosis – iron deposition in the lung
Coagulative disorders
Widespread metastasis – rare cause
May be idiopathic
What causes the pneumonia, abscess and/or lobar collapse seen in lung cancer
Airway obstruction
What are the common symptoms of COPD
Cough, usually worse in the mornings and productive with a small amount of colourless sputum
Breathlessness - most significant symptom, but usually does not occur until later on in disease
Wheezing: particularly during exertion and exacerbations
What do smokers macrophages look like
Abundant cytoplasm containing dusty brown pigment
Some macrophages have lamellar bodies (contain surfactant) within phagocytic vacuoles
List the macroscopic features of Group 4 PH (CTEPH)
Yellow clots that contain collagen, fibroblasts, elastin, inflammatory cells and recanalization vessels.
Stenosis and occlusion where the original PE was, usually with webs and bands.
Vascular remodelling including hypertrophy and intimal thickening.
How does activation of the inflammatory response affect the development of dust-borne diseases
Innate immune response increases intensity & duration of local reaction
It is triggered by the phagocytosis of certain particles by macrophages
Describe the differentiation of malignant neoplasia’s
Poorly-differentiated
Exhibiting little or no evidence of differentiation
Describe the blood supply to growing tumour cells
They must have a supply in order to grow
However there is insufficient vascular stroma
The tumour can develop areas of ischemia necrosis as a result
Describe the trends in asthma mortality
There has been worldwide reduction in asthma mortality in adults and children over the past 25 years due to introduction of effective treatment (particualrly inhaled steroids)
However, there is major disparity between countries
Still causes may deaths - 417,918 deaths globally in 2016
What is the survival rate in Group 1 PAH
Life threatening if not treated
5-year survival rate of 57% without treatment
This drops to 1 year if they have right sided heart failure
What are asbestos bodies
Long, thin asbestos fibres with translucent centre and gold-brown colour
Describe the loss of polarity seen in malignant tumours
The orientation of anaplastic cells with respect to each other or to supporting structures like basement membranes (their polarity) is markedly disturbed
Sheets or large masses of tumor cells grow in a disorganized fashion
List potential complications of respiratory failure which are seen in the kidneys
Acute renal failure which can cause electrolyte and acid base disturbance
What is dysplasia
Disordered growth
Where does small cell lung carcinoma typically occur
Most commonly occur centrally in major bronchi, but can also be more peripheral
Describe the presentation of subacute fibrotic lung diseases
Have a resolving, remitting, relapsing or progressive course
Presentations with a variable course are typified by COP (weeks/months of prodromal flu symptoms; SOB + exercise intolerance).
Can recur when steroids are withdrawn/tapered
In situ epithelial cancers display all the cytologic features of malignancy - true or false
True
If not treated they have a high probability of progressing to invasive cancer
How might diffuse alveolar haemorrhage appear on CXR
May vary based on underlying cause
Diffuse infiltrative opacification pattern
Typically in the mid zones with apical sparing
Define each M stage in the TMN staging system (general cancer)
M0- no distant metastasis
M1 - metastases present
Define type 1 respiratory failure
PaO2 < 8kPa
Normal or low CO2
What causes honeycomb fibrosis
Seen in IPF
Destruction of the alveolar architecture
This leads to the formation of cystic spaces lined by hyperplastic type II pneumocyte or bronchiolar epithelium
Describe the differentiation of benign neoplasia’s
They are well-differentiated
Rare mitoses, of normal configuration
e.g. lipoma only the growth is abnormal
What is the most common type of pulmonary hypertension?
Group 2 PH caused by left-sided heart failure
What are the 3 main mechanisms behind respiratory failure (generally)
V/Q mismatch
Hypoventilation
Shunting
A person with CTEPH will likely have what in their clinical history
History of PE and/or the relevant risk factors for both PE and CTEPH
Describe lepidic lung adenocarcinoma
Pneumocyte type neoplastic cells track along normal alveolar structure
Why are patients with emphysema called pink puffers
Patients develop muscle wasting and weight loss
Due to low cardiac output and hypoxia
Will be breathing fast
What is the most common form of asthma
Atopic or allergic asthma
Presen
List the macroscopic features of asthma
Oedema
Congestion
Bronchial stenosis
Mucus hypersecretion
Seen in peripheral airways via scope
How can you group fibrotic lung diseases
Chronic
Subacute
Acute
List examples of chest wall disorders
Severe obesity
Pleural diseases (e.g. trapped lung, scarring, large pleural effusions, chronic empyema)
Kyphoscoliosis
Neuromuscular diseases (e.g. MG, ALS, myopathy)
How can COPD lead to Group 3 PH
Causes prolonged hypoxic vasoconstriction, mechanical stress, inflammation and endothelial dysfunction
All contribute to increased pressure
Which lung cancers could be classed as T4
Tumour > 7cm
OR
Involvement of the mediastinum, heart, great vessels, trachea, oesophagus, recurrent laryngeal nerve, vertebral body or carina OR
Separate tumour nodules in a different ipsilateral lobe
What is meant by the terms: tumour, mass or lesion
A growth or enlargement which may not be neoplastic (e.g. a granuloma)
Do benign neoplasms spread
No
Who is most affected by pulmonary haemorrhage
Children more than adults
Appears to affect children of all ages
Particualrly dangerous in premature babies or those with a low birth weight (high mortality in this group)
How do you treat pulmonary haemorrhage
It depends on the exact underlying cause and the severity.
Very premature babies or critically ill patients may require ventilation.
Blood transfusion if the bleed is severe.
Underlying disease managed as per individual guidelines. (e.g. steroids for CTD, Goodpasture’s etc)
If bleeding is coming from one site, it may be surgically embolised (blocked).
How do you manage the heart failure in cor pulmonale
Salt restriction Diuretics Positive inotropes Ace inhibitors Cardiac resynchronisation therapy and mechanical ventricular assist devices
Describe the general pathogenesis of COPD
Pathologic mechanisms not clear cut – few hypotheses
Abnormal inflammatory response to inhaled particles
Changes occur in central and peripheral airways and parenchyma
This leads to airflow limitation
List factors which increases your risk of developing CTEPH following a PE
Recurrent PE, large perfusion defects, high PA pressure at time of PE or an idiopathic PE
Non-O blood group - 77% of CTEPH patients
Splenectomy
Hypothyroidism
Both activate platelets
Ventriculoarterial shunt Infected intravenous catheters/devices Chronic inflammatory disorders Malignancy Abnormalities in blood components
Is there a gender difference in asthma
YES
Among children, asthma prevalence is higher in boys (due to smaller airways relative to lung size)
However, it switches during adolescence with prevalence being around 20% higher in women than men (same reason reverses)
How are tumours classified
Based primarily on the parenchymal component of the tumour itself
List ‘other’ diseases that can cause cor pulmonale (i.e. not lung pathology)
Cerebrovascular diseases Obstructive sleep apnoea Scleroderma CF Obesity associated hypoventilation
List potential complications of respiratory failure which are seen in the lungs
Pulmonary Fibrosis Pneumothorax Nosocomial pneumonia Ventilator dependency PE - due to acute RF
How do you perform a pulmonary thromboarterectomy
Median sternotomy is performed
Patient is put into hypothermic circulatory arrest for the surgery
The thrombi are then dissected out of the vessels.
What is pleomorphism
Variation in cell size and shape
Ranges from small cells within an undifferentiated appearance to tumor giant cells
What are the 3 main subtypes of pulmonary haemorrhage
Diffuse pulmonary haemorrhage - diffuse bleeding into lung
Diffuse alveolar haemorrhage - if the bleeding is into the alveolar spaces
Localised pulmonary haemorrhage - haemorrhage is restricted to a focal region of the lung
This can range from a small focus to a whole lobe
Which features of respiratory failure suggest a poor prognosis
ARDS or COPD being the underlying cause
Type 2 respiratory failure as patients tends to have chronic lung disease and renal, hepatic, neurological and cardiopulmonary co morbidities
How many groups of pulmonary hypertension are there (as defined by the WHO)?
5
6 if you include the paediatric subtype but not an official group
What increases risk of parenchymal lung disease
Exposure to dust, metals, organic solvents, and agricultural jobs.
List the microscopic features of emphysema
Abnormal large alveoli separated by thin septa with focal centriacinar fibrosis
Loss of alveolar walls and dilatation of airspaces
What features may be seen in dysplastic epithelial surfaces
Architectural disarray
A loss of orderly differentiation
List the macroscopic features of Group 3 PH
Depends on the underlying lung disease
E.g., hyperplasia of mucus glands and emphysema seen in COPD
What causes non-atopic asthma
Triggers are less clear
Possibly viral infection or air pollutants
What causes the haemoptysis seen in lung cancer
Haemorrhage into the airways
What factors suggest a poor prognosis in Group 1 PAH
Male sex
Age over 50
Right ventricle dysfunction
Poor functional status (as defined by WHO)
Describe the structure of the granulomas that occur in sarcoidosis
They are well-formed non-necrotising granulomas containing aggregates of tightly clustered epithelioid macrophages (often with giant cells)
In chronic cases the granulomas become enclosed within fibrous rims or may eventually be replaced by hyaline fibrous scars.
What is the typical survival rate in IPF
Median survival 3.8 years after diagnosis
Diseases most similar to IPF have a mortality rate of approx. 50% at 5 years
How might diffuse pulmonary haemorrhage appear on CT
Ground glass opacification
+/- crazy paving pattern (ground-glass opacity with superimposed interlobular septal thickening and intralobular septal thickening)
May have areas of consolidation
Diffuse nodular densities on HRCT in the subacute phase
How does CTEPH present on CT/MRI
Presence of thrombi and occlusion
Enlarged vessels
List the characteristics of a benign tumour
Not harmful and not cancer - rarely fatal
Localized at their site of origin
Does not invade nearby tissue or spread to other parts of body (no mets)
Slow growing
Well differentiated - often resemble origin tissue
Well circumscribed and encapsulated
Generally amenable to surgical removal
What causes the dyspnoea seen in respiratory failure
The excessive respiratory effort, hypoxia and hypercapnia affect the vagal receptors
What is the common mechanism of death from asthma
Asthmatics are at increased risk of respiratory failure - occurs when not enough oxygen is transferred to blood
Seen after life-threatening asthma attacks
If respiratory failure isn’t treated immediately, it can lead to death
Asthma patients might be at a greater risk of suffering cardiovascular and cerebrovascular diseases
How does hypersensitivity pneumonitis present on pulmonary function tests
Acute restrictive pattern of lung function tests
Symptoms occur 4-6hrs after exposure, can last 12hrs-several days.
Will happen again re-exposure to antigen
List the common inhaler therapies used in COPD
Start with a short acting bronchodilator as required
Double therapy refers to a combination of LAMA, LABA and ICS (LAMA/LABA for those without asthmatic features and LABA/ICS for those with)
Then move to triple therapy - LAMA/LABA/ICS
What microscopic feature may be seen in acute exacerbations of IPF
Diffuse alveolar damage
May be super-imposed on the chronic changes
Which PAH patients are treated with vasodilators
Group 1 PAH
Given to those who respond to the vasodilator reactivity tests
Why must a pathologist be informed of the location of a biopsy sample
So that they can ensure it is the correct cell type for that location
E.g. A sample of gastric mucosa is normal for the stomach but if it’s from the bottom of the oesophagus its suggestive of metaplasia and comes with risks
List the pathological changes seen in the proliferative phase of ARDS
Granulation tissue will form in the alveoli and their walls
Type 2 pneumocytes will proliferate
The granulation tissue can then either resolve causing little functional issues or it can cause fibrotic scarring in the alveolar septae
This becomes the late fibrotic stage of ARDS
What name is given to malignant tumours arising in solid mesenchymal tissues
Sarcomas
The pathological findings of cor pulmonale are the same as which other condition
Right heart failure caused by left heart failure
In which disease would you see Schaumann bodies
Sarcoidosis - characteristic
Also seen in other granulomatous diseases like TB
How does smoking affect the development of dust-borne diseases
It worsens effects of all inhaled mineral dusts, but particularly those due to asbestos
If the pulmonary artery becomes enlarged due to PAH what symptom can it cause
It can cause hoarseness if it compresses the laryngeal nerve
List the macroscopic features of emphysema
Voluminous lungs - overlap the heart
Upper 2/3 of lung most affected
Alveoli can be seen on the cut surface of lung
Apical blebs and bullae are indicative of severe disease
List some potential complications of lung cancer
SVC syndrome
Horner’s syndrome
Paraneoplastic syndromes
Lambert-Eaton Syndrome
What is the main cause of Group 1 PAH
Worldwide it is schistosomiasis - around 7% of sufferers develop it
In Europe most cases are idiopathic as Schis not endemic there
Which CTEPH patients are most likely to get surgery
It is based on underlying disease and where their clots are
Larger proximal clots are ideal as easier to remove so more likely to get operated on
Lots of small, distal clots may not get as much benefit from surgery
Also depends on patient fitness
List the microscopic features of asthma
Airway remodelling (detail in another card)
Curschman spirals in sputum or bronchoalveolar lavage specimens
Numerous eosinophils and Charcot-Leyden crystals- look like growing crystals
Discuss the prevalence of COPD
The Global Burden of Disease Study reports a prevalence of 251 million cases globally in 2016.
COPD is likely to increase in coming years due to higher smoking prevalence and aging populations in many countries
List the causes of non-idiopathic interstitial pulmonary fibrosis
Occupational exposure (asbestosis, silicosis, etc.) Environmental antigens (farmer’s and pigeon-fancier lung, etc.) Drugs ± radiation Systemic illness (Hep C, HIV, IBD)
What is hypersensitivity pneumonitis
A spectrum of immunologically mediated, mostly interstitial lung disorders, caused by intense, often prolonged, exposure to inhaled organic antigens
What is CTEPH
Chronic thromboembolic pulmonary hypertension
This is PH with organized, nonacute, thromboembolic material and altered vascular remodeling in the pulmonary vasculature
It is a rare but dangerous complication of PE
How does particle uptake by EC and travel across linings affect the development of dust-borne diseases
This allows direct interactions with fibroblasts & interstitial macrophages which can trigger immune responses
Some particles may reach lymph nodes via lymphatic drainage directly or migrating macrophages triggering the adaptive immune response
List some of the cause specific treatments used in respiratory failure
Bronchodilators in asthma
Corticosteroids if airway swelling and inflammation
Physical therapy and pulmonary rehab after the event especially if were on ventilator
NG/parenteral feeding if ventilated
How do lung diseases cause increased pulmonary hypertension
Most commonly cause hypoxemia chronically which leads to vasoconstriction and smooth muscle hypertrophy in the lungs vasculature as well as reduced NO
Diseases of the pulmonary vasculature will cause PH
COPD, bullous disease and PE’s will destroy capillary beds raising pressure
COPD and mechanical ventilation will increase alveolar pressure causing PH
Describe the histological signs of progressive silicosis
the early nodules coalesce into hard, collagenous scars (some soften and cavitate centrally due to superimposed TB or ischaemia)
Hallmark histologically = central area of whorled collagen fibres w/ peripheral zone of dust laden macrophages.
Nodules show weakly birefringent silicate particles on polarised microscopy
List potential complications of non-invasive ventilation
Gastric aspiration can cause a pneumonia on top of an already diseased and struggling lung
What are the characteristic features of asthma
Reversible airflow obstruction caused by bronchial hyperresponsiveness to a variety of stimuli as well as airway inflammation
Chronic inflammation can lead to airway remodelling which is irreversible and causes permanent damage
Variable and recurring symptoms
COPD is most common in which patients
Long standing tobacco smokers
Air pollutants may also contribute
Is there geographical variation in COPD
More than 90% of COPD deaths occur in low and middle income countries
List the microscopic features of complex coal worker’s pneumoconiosis
Dense collagen and pigment
Has a centre of lesion often necrotic (local ischaemia)
What is an adenoma
Benign neoplasm of the epithelial linings of ducts and glands
List potential complications of invasive ventilation
Ventilator associated pneumonia Ventilator associated lung injury Pneumothorax Pulmonary oedema Hypoxemia due to lung damage
There are no specific pathological findings for respiratory failure - true or false
True
The pathological findings would be those of the underlying condition causing the respiratory failure
What is the most common primary lung cancer in never-smokers
Adenocarcinoma
Metaplastic epithelium is prone to malignant transformation - true or false
True
How does high altitude contribute to Group 3 PH
Long exposure causes hypoxia which in turn causes vasoconstriction
How is cardiac catherisation used in PAH
Definitive diagnostic test
Also used to perform vasodilator tests
How do you treat the underlying lung pathology in cor pulmonale
Each pathology will have its own specific treatment
Any that cause chronic hypoxia will get O2 therapy
List the typical clinical features of Group 1 hypertension
Typically symptoms are related to the underlying cause
The PH itself can cause the following non-specific symptoms: Dyspnoea on exertion Fatigue Syncope (on exertion) Chest pain Anorexia RUQ pain
If it progresses to RHF you may see the associated congestive symptoms
May also develop murmurs - splitting of second HS or systolic ejection
List disorders affecting the neural drive of respiration that can be the underlying cause of respiratory failure
Drugs can depress it - narcotic and sedative overdose
Structural changes - tumours/vascular abnormalities in the brainstem
Metabolic abnormalities - myxoedema and chronic metabolic alkalosis
Why might an occupational lung disease patient get an autopsy
They are often reported to fiscal so get one
You can get compensation for certain occupational diseases such as asbestosis
Describe the features of carcinoma in situ
Severe dysplasia
Involvement of full thickness of epithelium
No penetration of basement membrane
Irreversible
What is the FEV1
Forced expiratory volume at one second
How much can you exhale in one second
List the macroscopic features of bronchiectasis
Affects lower lobes bilaterally
The dilated bronchi appear cystic and are filled with mucopurulent secretions
The lung cancer risk from asbestos exposure can be further increased by which other factor
Smoking
5x risk in asbestos alone
55x higher risk if they are also a smoker
How do you treat Group 2 PAH
Optimise blood pressure through medication and lifestyle.
Patients can stay active but should avoid strenuous exercise
Typical heart failure treatment applies such as diuretics (loop), ACE or ARBs and beta-blockers.
Vasodilators haven’t been proven to be effective in this group yet.
If causes by valve disease you can get valve replacement/repair.
Cardiac transplant may be considered if medication is not effective.
What are the macroscopic features of IPF
Cobblestoned pleural surface due to retraction of scars along interlobular septa
Cut surface will be firm with rubbery white areas of fibrosis
Lower lobes, subpleural regions & interlobular septa, affected preferentially.
List the common symptoms of hypersentivity pneumonitis
Will have an acute attack following exposure to antigen
Includes fever, SOB, cough, leucocytosis
Describe the typical clinical course of chronic respiratory failure
Tends to be less evident than the acute form
Lasts a long time
Usually has no cure
Requires lifelong management
Describe the pathophysiology of cor pulmonale
Lung disease cause an increase in pulmonary vascular resistance and arterial pressures - pulmonary hypertension
Afterload increases
Right heart has to work harder to overcome the afterload
This leads to hypertrophy and subsequent dilatation - leads to HF
The strain on the right heart is worsened by chronic hypoxia causing polycythemia which increases the blood viscosity increasing the work of the heart again
How might acute phase diffuse alveolar haemorrhage appear on CT
The acute phase ranges from lobar areas of ground glass opacification to consolidation.
Dark bronchus sign – bronchi appear darker than the surrounding ground glass opacities
What are the common physical signs of COPD
Tachypnea and respiratory distress with simple activities
Use of accessory respiratory muscles and paradoxical indrawing of lower intercostal spaces (Hoover sign)
Cyanosis
Elevated jugular venous pulse (JVP)
Peripheral oedema
Which lung cancers could be classed as N2
Metastasis to ipsilateral mediastinal or subcarinal lymph nodes
What feature of mitoses is suggestive of malignancy
Atypical, bizarre, mitotic figures
What is Acute interstitial Pneumonia (AIP)
It is a viral prodrome syndrome
It’s idiopathic
Excludes those with ARDS which has an identifiable cause and those with underlying fibrotic lung disease or systemic disorders
List the different types of diffuse parenchymal lung disease
Idiopathic interstitial pneumonias Non-idiopathic interstitial pulmonary fibrosis Granulomatous disease PLCH Eosinophilic pneumonia
How are malignant neoplasms named
Same as benign neoplasms + certain additions
Named after cell origin
List the features of dysplasia
May exhibit considerable pleomorphism
Reversible
Contain large hyperchromatic nuclei with a high N:C ratio
More abundant mitotic figures may be seen
Undifferentiated cancers often contain many cells in mitosis - true or false
True
They usually have a high rate of proliferation
What is the most common malignancy in those exposed to asbestos
Lung cancer (5x increased risk) Mesothelioma is actually very rare even with exposure
What is the major complication of Group 2 PAH
The backpressure can lead onto RVF
Which lung cancers could be classed as T1
Tumour ≤ 3cm without pleural or mainstem bronchus involvement
What are the general symptoms of interstitial lung disease
Dyspnoea, tachypnoea, dry cough, end-inspiratory ‘velcro’ crackles
Hypoxemia, cyanosis and clubbing can occur, but late stage in disease course
What is the definition of pulmonary haemorrhage
The term can be used for any form of bleeding from the lung, respiratory tract or alveoli
Describe shunting
Deoxygenated blood passes the alveoli without being oxygenated due to abnormalities in the alveoli
It then mixes with oxygenated blood that’s come through ventilated alveoli which causes the hypoxemia
Occurs when there is a disease of the alveoli themselves that prevents the gas exchange such as pulmonary oedema, pneumonia, pulmonary haemorrhage or atelectasis
List the different types of idiopathic interstitial pneumonias
Idiopathic pulmonary fibrosis (IPF) - most common
Non-specific interstitial pneumonia (NSIP)
Cytogenic organising pneumonia (COP)
Acute interstitial pneumonia (AIP)
Desquamative interstitial pneumonia (DIP)
Respiratory bronchiolitis-associated interstitial pneumonia
Lymphoid interstitial pneumonia
What causes silicosis
Inhalation of the proinflammatory crystalline silicon dioxide
Also called silica
How might diffuse alveolar haemorrhage appear on CT in between chronic bleeds
Intralobular lines and thickening on top of the ground glass
May have the crazy paving pattern
How do you treat Desquamative interstitial pneumonia (DIP) and Respiratory bronchiolitis-associated interstitial lung disease
DIP responds well to steroids
Both are helped by smoking cessation
Describe the early histological signs of silicosis
Tiny, hardly palpable, discrete pale-black (if coal present) nodules in hilar lymph nodes & upper zones
What is the most common symptom of cor pulmonale
Exertional dyspnoea
How does particle solubility and cytotoxicity affect the development of dust-borne diseases
Linked to particle size
Small particles made of harmful substances of high solubility = more likely to produce rapid-onset acute lung injury
Larger = more likely to resist dissolution & persist within lung parenchyma for years – tend to evoke fibrosing collagenous pneumoconioses
What is the main aim of treatment for cor pulmonale
Treat the underlying lung pathology and the heart failure
Variety of drugs used, O2 therapy, salt restriction and some surgical options
List the microscopic features of chronic bronchitis
Chronic inflammation of airways seen as:
Presence of lymphocytes and macrophages
Thickening of bronchiolar wall due to smooth muscle hypertrophy
Deposition of extracellular matrix in muscle layer
Peribronchial fibrosis
Goblet cell hyperplasia
Enlargement of mucus secreting glands
How can you treat Group 1 PAH
O2 therapy - can reduce mortality Diuretics (loop are 1st choice) Digoxin Anticoagulants Vasodilators are given to some Lung transplantation is reserved for patients with severe cases
What is a meningioma
A benign neoplasm of brain coverings
List the histological features of Cryptogenic Organising Pneumonia (COP)
Polyploid plugs of loose organising CT (Masson bodies) within alveolar ducts, alveoli & bronchioles
Connective tissue all the same age and underlying lung normal
No interstitial fibrosis or honeycombing
Which part of the lung is most affected in COPD
upper two thirds most commonly affected due to smoking (smoke rises)
How does particle size affect the development of dust-borne diseases
Smaller particles can reach terminal small airways, air sacs and deposit in linings
Most dangerous particles are 1-5micrometre in diameter
How do you diagnose Group 1 PAH
Diagnosis of exclusion
ECG and chest radiographs - may show ventricular dysfunction which suggests PAH
A trans-thoracic echo with Doppler - used to measure PA pressure and assess ventricles.
Definitive test is right-sided cardiac catherisation
Further tests dependent on underlying cause
What is the mechanism of death in Group 1 PAH
Most common cause of death is RHF (can lead to sudden cardiac death or arrhythmias)
Dilation of the PA can cause dissection/rupture and compression of the left coronary artery.
Describe the trend in the prevalence of lung cancer
Has been decreasing for both men and women since the 1950s
List the different histological subtypes of lung adenocarcinoma
Lepidic Acinar Papillary Micropapillary Solid
Describe an invasive carcinoma
Affects the surrounding tissues
Penetrate the basement membrane
List the common symptoms of lung cancer
Weight loss Fever Cough Haemoptysis Chest pain Pneumonia, abscess, lobar collapse Hoarseness Diaphragm paralysis
How can CTEPH cause death
If untreated it can progress to right ventricular failure and/or severe hypoxemic respiratory failure.
Respiratory failure may require ventilation.
Can lead to cardiogenic shock and death.
Death due to shock or the other complications of RHF
Describe the onset of late-onset asthma
Occurs in those aged 12-65
It is more severe, and associated with a faster decline in lung function, particularly in patients with a smoking history
Includes occupational asthma
How does COVID-19 interstitial pneumonia affect lung function
It makes it abnormal
May see restrictive abnormalities, reduced diffusion capacity, small airways obstruction
The abnormalities seem to be related to acute, severe episodes with high levels of inflammatory markers
Describe the pathogenesis behind sarcoidosis
Includes several immunologic abnormalities suggesting cell-mediated immune response to unidentified antigen
Exact cause unknown
Includes intra-alveolar & interstitial accumulation of CD4+ T cells
Raised levels of T cell-derived Th1 cytokines
High levels of cytokines favour recruitment of more T cells + monocytes which can lead to granuloma formation
Impaired dendritic cell function
How does COVID-19 interstitial pneumonia present on imaging
Patients who have respiratory deterioration show ground-glass opacities on chest CT
Fibrotic abnormalities
Which condition increases your genetic susceptibility to COPD
Alpha 1-antitrypsin deficiency
This is a deficiency in an elastase which should protect the lungs from elastic breakdown
Without it you get early onset emphysema
How do you treat Group 3 PH
Treatment is directed at the underlying lung disease.
Ideally treat this early to prevent progression to or of the pulmonary hypertension.
CPAP can reduce pressures in those with OSA – potentially reverses PH.
Inhaled vasodilators can be used in COPD patients to improve V/Q matching.
In which lung disease would you see eggshell calcification
Silicosis
Small cell lung carcinoma is highly malignant - true or false
True
There is virtually no pre-invasive phase
2/3 present with distant metastases – median survival of 10 months
How do you manage asthma
Start with SABA alone
Then offer a low dose ICS as maintenance
Then introduce a LTRA in addition to ICS and review response
If asthma is uncontrolled on this then offer aLABAin combination with the ICS, and review LTRA treatment
Some more targeted treatments are available for specific types of asthma such as monoclonal antibodies
How does environment affect the prevalence of asthma
Has been shown to alter prevalence
Migrants from low prevalence areas to high areas will initially have the lower prevalence compared to native people but the incidence rises to a similar proportion with increasing length of stay
What pathological features may you find in the liver and portal system of someone with cor pulmonale
Congestive hepatomegaly
Nutmeg liver – pericentrally red and congested, periportally normal and tan
Splenomegaly and platelet sequestration
GI tract congestion and oedema
Squamous cell lung carcinoma metastasizes late - true or false
True
Can be associated with better outcomes as a result
Describe the histological appearance of squamous cell lung cancer
‘Cobblestone’ appearance of polygonal cells
Tumours may have central cavitation
May see keratinisation with a central pearl
Describe the pathogenesis of chronic bronchitis
Initiated by exposure to noxious chemicals which leads on to:
Mucus hypersecretion
CFTR dysfunction- acquired by smoking, abnormal dehydrated mucus
Chronic inflammation
Infection
What name is given to a malignant neoplasm of the blood vessels
Angiosarcoma
What is implied by the use of the term cancer
This implies malignancy
What is anthracnosis
Form of pneumoconiosis
Most innocuous coal-induced lesion
Seen to some extent in city living & smokers)
List the microscopic features of Group 1 PAH
Endothelial dysfunction.
Decreased vasodilator production (prostacyclin, NO) and an increase in vasoconstrictors (endothelin).
Plexiform lesions
What causes the Curschman spirals seen in asthma
They occur due to extrusion of mucus plugs from sub-epithelial mucous gland ducts or bronchioles
Will be seen in sputum of bronchoalveolar lavage specimens - look like long thing spirals (string?)
In which tissues/organs are carcinomas in situ commonly seen
Skin
Breast
Bladder
Uterine cervix
Through what mechanisms can respiratory failure be fatal
Multiorgan failure (heart, brain, kidneys) due to inadequate O2 Sepsis Pulmonary dysfunction can be enough on its own Due to complications of respiratory failure (arrhythmia, MI, heart failure, GI haemorrhage, AKI, brain injury and death, heart failure, endocarditis)
Typically what colour is lung cancer
Yellowish/grey
Describe the progression of asbestosis
It is rare <10y from exposure
More common presents after 20-30y
Disease can remain static or progressive to respiratory failure etc
When does metaplasia occur
Always found in association with tissue damage, repair and regeneration
The tissue type can change to one better suited to the local environment - e.g. Barret’s oesophagus
What is the TNM staging system
The system used to stage all cancers
T refers to the tumour itself and ranges from Tis-T4
N refers to nodes and ranges from N0-N3
M refers to metastasis and ranges from M0-M1
In which lung disease would you see whorled collagen fibres with peripheral zone of dust-laden macrophages
Silicosis
What causes respiratory failure
It happens when gas exchange within the lungs is inefficient
This causes hypoxia and potentially hypercapnia
What proportion of IPF patients have PH
28-46%
What are the 3 main categories of lung cancers
Small cell - 15% of cases
Non-small cell
Metastases
How does the prevalence of asthma vary geographically
The prevalence is highest in developed countries and lowest in developing countries
However, rates in developing countries may be underestimated and is increasing rapidly in as lifestyles become westernized and more urbanized
Stable or decreasing rates in developed countries
What is cor pulmonale
Right heart failure that is caused by a lung pathology
not left heart failure
What are the 4 main subtypes of asthma
Atopic
Non-atopic
Drug induced
Occupational
How can you differentiate between an old and recent fibrotic lesion in IPF
Earliest lesions identified by exuberant proliferation of fibroblasts (foci)
As time goes on these become more fibrotic and less cellular
List the microscopic features of Group 2 PAH
Intimal fibrosis and myofibroblast proliferation
Increased pressure and endothelial changes cause a release of growth factors which increase elastin production
When does allergic asthma usually present
Usually presents in childhood
Commonly associated with eczema, rhinitis, orfood allergy, a family history of asthma (atopy)
Presents with wheezing and coughing with and between viral infections
Which blood abnormalities increase your risk of developing CTEPH
Abnormal fibrinogen structure
Elevated factor VIII, von Willebrand factor, or type 1 plasminogen activator inhibitor
Elevated lipoproteins
What pathological features may you find in the body cavity of someone with cor pulmonale
Pericardial and pleural effusions
Ascites
Caused by the increased pressure
What is senescence
Deterioration with age / loss of a cell’s power of division and growth
Linked to telomere loss
What results would be expected on the spirometry of a patient with restrictive lung disease
Normal FEV1:FVC ratio - >70% expected Variable FEV1 Reduced FVC Total lung capacity is reduced Reduced residual volume Normal airway resistance
What name is given to a malignant neoplasm of the brain coverings
Invasive Meningioma
How does hypersensitivity pneumonitis present on CXR
Multinodular interstitial infiltrates
Describe SVC syndrome
Obstruction of the superior vena cava leads to facial swelling, dyspnoea, cough and orthopnoea
Describe the general pathogenesis behind diffuse parenchymal lung disease
Thought to begin with an acute injury to the pulmonary parenchyma
This leads to chronic interstitial inflammation
This results in -> fibroblast activation and proliferation with eventual pulmonary fibrosis + tissue destruction
What is the most common cause of pulmonary haemorrhage
Pulmonary vasculitis
Describe the epidemiology of group 1 PAH
Estimated 6.6-26 cases per million adults in Europe
Women are more likely to be affected (65-80% predominance)
Average age at diagnosis is 50s
No clear race predominance
How does CTEPH present on chest radiography
May be normal until disease progresses
Right ventricular enlargement
Areas of lung hypoperfusion or infarction (Westmark sign and Hampton hump)
In which part of the lung does adenocarcinoma typically occur
Tend to occur peripherally
What are the main mechanisms behind type 1 respiratory failure
Type 1 is caused by V/Q mismatch, hypoventilation and shunting
What causes the hoarseness seen in lung cancer
Recurrent laryngeal nerve invasion
List the common oral therapies used in COPD
Prophylactic antibiotics
Theophylline
Corticosteroids - keep dose as low as possible and long term use not usually recommended
Mucolytics - if chronic sputum production
Roflumilast - long-acting inhibitor of the enzyme phosphodiesterase-4.
What causes Horner’s syndrome
Caused by pancoast tumours at lung apices infiltrating the sympathetic ganglia
Which occupational lung disease features pleural plaques
Asbestosis
How do you name benign tumours of epithelial cells
Some based on the cell of origin
Others are based on their microscopic appearance/macroscopic architecture
What are the clinical characteristics of emphysema
Patients may be very thin with a barrel chest
Patients typically have little or no cough or expectoration
Severe dyspnoea from early on
Breathing may be assisted by pursed lips and use of accessory respiratory muscles; patients may adopt the tripod sitting position
The chest may be hyper resonant, and wheezing may be heard
Heart sounds are very distant
Describe the epidemiology
The prevalence can’t be known because it is a syndrome not its own disease
List the pathological changes seen in the late fibrtoic phase of ARDS
Fibrotic scarring in the alveolar septae
List the types of granulomatous diffuse parenchymal lung disease
Sarcoidosis
Hypersensitivity pneumonitis
What is obstructive lung disease
Refers to a group of diseases characterized by an increase in resistance to airflow due to diffuse, widespread airway disease
Can affect any level of the respiratory tract
What name is given to a benign neoplasm of the connective tissues (fibrous tissues)
Fibroma
What are the histological features of Acute interstitial Pneumonia (AIP)
Diffuse alveolar damage with subsequent fibrosis
DAD cause lung to be firm and rubbery
List potential complications and subsequent cause of death in diffuse parenchymal lung diseases (DPLDs)
Progressive respiratory failure Cor pulmonale Pulmonary embolism Pneumothorax Super-imposed infections, e.g. pneumonia, TB Bronchogenic carcinoma
What are the 5 WHO groups of pulmonary hypertension
Group 1 - Pulmonary arterial hypertension (PAH)
Group 2 - Pulmonary hypertension due to left-sided heart disease
Group 3 - Pulmonary hypertension due to lung diseases and/or hypoxia
Group 4 - Chronic thromboembolic pulmonary hypertension (CTEPH)
Group 5 - Pulmonary hypertension with unclear or multifactorial aetiologies
There is also a paediatric-specific category which includes persistent pulmonary hypertension of the newborn.
What are the principles of management of respiratory failure
Treat the underlying condition
AND
Correct the hypoxaemia with O2 management
However, care needs to be taken with O2 management in type 2 respiratory failure - reduces hypoxic drive
What results would be expected on the spirometry of a patient with obstructive lung disease
Reduced FEV1:FVC ratio - <70% expected Reduced FEV1 Normal FVC Total lung capacity normal or increased Normal or increased residual volume
Which conditions can cause subgroup 4 in Group 1 PAH (e.g. conditions which cause localised lesion in the arterioles)
CREST, congenital L-R shunts, portopulmonary hypertension, HIV associated PAH and schistosomiasis
What are the most common causes of management complications in the treatment of respiratory failure
O2 therapy
Invasive ventilation
Which diffuse alveolar lung diseases are associated with smoking?
DIP and RB-ILD
Both respond to cessation
What is a squamous cell carcinoma
Malignant neoplasm of stratified squamous epithelium
Which areas of the body most commonly present with sarcoidosis
Most common clinical presentation is bilateral hilar lymphadenopathy or parenchymal lung involvement.
2nd most common – eye and skin lesions.
List the microscopic features of Group 4 PH (CTEPH)
Microthrombi
Plexiform lesions
In which cells is dysplasia principally found
Epithelial cells
Describe the structure of Schaumann bodies
Laminated concretions of Ca & proteins
Asteroid bodies = stellate inclusions
Both found within giant cells in 60% of non-necrotising granulomas
List potential complications of respiratory failure which are seen in the heart
Heart failure
Arrhythmia
MI
In acute RF particularly: Reduced CO Hypotension Arrhythmia Endocarditis MI
Give an example of a marker of disease activity in sarcoidosis
High levels of TNF in the bronchoalveolar fluid
It is releases at increased levels by activated alveolar macrophages
How does squamous cell lung cancer form
Starts as squamous metaplasia in bronchial epithelium
This leads to carcinoma in situ
Give examples of obstructive lung diseases
Cystic Fibrosis Bronchiectasis Asthma Bronchitis (chronic) Emphysema
Last 2 combine for COPD
Describe the features of asbestosis
Get fibrosis around respiratory bronchioles and alveolar ducts (adjacent alveolar sacs + alveoli can be affected)
Diffuse interstitial fibrosis
Causes distorted architecture - enlarged airspaces enclosed by thick fibrous walls
Eventually honeycombing occurs
Similar pattern of fibrosis as UIP
Diffuse pulmonary interstitial fibrosis with asbestos bodies
Which disease presents with patchy submucosal infiltrate of lymphocytes & histocytes
Respiratory bronchiolitis-associated interstitial lung disease
List the main symptoms of asthma
Wheezing
Shortness of breath
Chest tightness and non-productive cough
All episodic
How do you treat CTEPH
Pulmonary thromboarterectomy is the definitive surgical treatment
If ineligible for the thromboarterectomy, then balloon angioplasty can be performed to improve flow and perfusion
It is recommended that patients go on lifelong anticoagulation (warfarin is typical choice)
What causes Group 3 PH
Other lung disease or hypoxia. This includes:
- COPD
- Interstitial Lung Disease (ILD) such as idiopathic pulmonary fibrosis.
- Sleep-disordered breathing disorders like obstructive sleep apnoea.
- Alveolar hypoventilation disorders
- Long exposure to high altitude
List common signs of cor pulmonale
Cyanosis Tachycardia Raised JVP Loud pan systolic murmur Ascites Peripheral oedema Hepatosplenomegaly
What is the prevalence of asthma
It is one of the most common chronic,non-communicable diseases worldwide
4% of global adult population diagnosed
List potential complications of respiratory failure which are seen in the brain
Irreversible brain damage and brain death
Which neuromuscular diseases can cause cor pulmonale
Myasthenia gravis
Poliomyelitis
MND
List the types of inflammation that asthma can be divided into
eosinophilic(allergic and non-allergic)
Non-eosinophilic (neutrophilic type 1 and type 17 and paucigranulocytic)
Mixed granulocytic inflammation
What is the normal nucleus:cytoplasm ratio
Between 1:4 and 1:6
List genetic changes that make you more susceptible to asthma
Chromosome 5q locus – near genes for IL-4, IL-5, IL-9, IL-13 and receptor for IL-4
Class 2 HLA alleles linked to production of IgE against some allergens
Mutations of genes encoding IL-33 and its receptor result in production of TH2 cytokines
Mutations of gene encoding TSLP which is a cytokine with a role in initiating allergic reactions
What are the 2 main subgroups of group 4 PH
Cases caused by chronic thromboembolic pulmonary hypertension (CTEPH)
Cases caused by other obstructive causes (e.g. tumours, congenital stenosis).
Describe the appearance of nutmeg liver
Pericentrally red and congested
Periportally normal and tan
What is squamous cell lung cancer associated with
Smoking
What is another name for small cell lung carcinoma
oat cell carcinoma
Describe the general prognosis for lung cancer
Generally poor as disease tends to be advanced when it presents
Overall 5-year survival rate of 18.7%
List potential complications of O2 therapy in respiratory failure
Patients with type 2 respiratory failure may use a hypoxic drive to drive their breathing (an effect of chronic hypercapnia)
O2 therapy can reduce this hypoxia and therefore reduce their breathing drive
What is the definition of differentiation (in regards to neoplasia)
The extent to which neoplastic parenchymal cells resemble the corresponding normal parenchymal cells morphologically and functionally
How does interstitial lung disease typically present on CXR
Bilateral small nodules
Irregular lines or ground-glass shadows all corresponding to areas of interstitial fibrosis.
Which lung cancers could be classed as M0
Those with no distant metastases
What pathological features may you find in the heart of someone with cor pulmonale
Right heart hypertrophy and dilatation
Left heart will be unaffected
Which intrinsic lung disease present in the younger age groups (20-40)
Sarcoidosis
Collagen-vascular-associated diseases
Pulmonary Langerhans cell histiocytosis
Describe the mortality trends in Group 2 PAH
Group 2 has a reduced survival compared to other types of PH.
Presence of PH in those with LHD leads to greater mortality.
What are the main pathological findings of cor pulmonale
Pericardial and pleural effusions Ascites Hepatosplenomegaly Nutmeg liver Pretibial pedal and presacral oedema GI tract oedema Pathological findings of underlying cause Hypertrophy and dilatation confined to the right side of the heart
Symptoms develop quickly in lung cancer - true or false
False
Usually insidious and non-specific leading to late diagnosis
How may PAH appear on a CXR
Enlarged pulmonary arteries
Reduction in blood vessels across the lung fields (oligemic)
May have right heart dilatation
What causes occupational asthma
Exposure to occupational antigens such as:
Fumes (resins)
Dusts (cotton)
Gases (toluene), chemicals (formaldehyde)
List the microscopic features of airway remodelling seen in asthma
Airway remodelling:
Thickening of the airway wall
Subbasement membrane fibrosis (deposition of type 1 and 3 collagen)
Increased vascularity, Increase in the size of goblet cells
Hypertrophy and/or hyperplasia of bronchial wall muscle
Increased extracellular matrix
What name is given to malignant tumours arising in epithelial cells
Carcinomas
List potential nutritional complications of respiratory failure
Malnutrition
Diarrhoea due to NG feeding
Hypoglycaemia and electrolyte disturbance due to parenteral feeding
List the common features of hypoxia
Dyspnea Restlessness Agitation Confusion Central cyanosis Tachycardia and arrhythmia Myoclonus Seizures
Describe the epidemiology of cor pulmonale
It’s exact prevalence is unknown
In the U.S. 6-7% of adult heart disease is CP
Countries with lots of smoking and air pollution will have higher prevalence’s as they will have higher rates of lung disease
Describe hypoventilation
The lungs are not being ventilated properly
Gradients of PaO2, PaCO2 and intra alveolar O2 remain normal
Instead caused by CNS damage and depression, chest wall and muscular issues
Patients with Group 2 PAH may have a history of what other conditions
MI, cardiomyopathy, hypertension or pericarditis
Explain how malignant neoplasms spread
Either by: Direct invasion of surrounding tissues Via the lymphatic system Via haematogenous spread Or by seeding
Idiopathic pulmonary fibrosis is rare in children - true or false
True
Most patients with IPF are >50 y/o
How does Group 3 PH progress
Increase in pulmonary pressure will eventually lead to heart failure
What complications can arise when treating COPD patients with O2
COPD patients may have chronic hypercapnia and therefore use hypoxia for respiratory drive
By giving them O2 you can remove this drive
If its home O2 therapy need to ensure they don’t smoke to avoid explosion
What is a haemangioma
A benign neoplasm of the blood vessels
Describe the pathology behind hypersensitivity pneumonitis
There is an abnormal sensitivity/heightened reactivity to antigen which leads to pathological changes involving alveolar walls
2/3 develop non-necrotising granulomas which suggest T-cell mediated (IV) hypersensitivity reaction
Can progress to severe chronic fibrotic lung disease if not addressed
Is is chronic bronchitis or emphysema that is associated with infection
Chronic bronchitis
Infections occur occasionally in emphysema but much more common in CB
List the potential pharmalogical treatments for diffuse parenchymal lung diseases (DPLDs)
Prednisolone ± cytotoxic agents (potential steroid-sparing effect) in some diagnoses.
Antifibrotic mediations, e.g., colchicine, cyclosporine, may reduce the rate of decline in FVC in patents with IPF.
In general, NSIP, DIP, & COP are more responsive to corticosteroids and immunosuppressives. UIP generally unresponsive to these.
Tyrosine kinase inhibitors and TGF-b antagonists have been shown to slow progression of IPF and are the only targeted therapy so far.
How does lung cancer incidence change with age
Incidence increases as age does
Peaks for both men an women in 70s
Starts decreasing for 80+
What causes the airway remodelling seen in asthma
Repeated inflammation due to allergen exposure
This leads to irreversible damage
Which is the most common idiopathic interstitial pneumonia?
IPF
What is metaplasia
Replacement of one type of cell with another type
What external pathological findings may be seen in a person with cor pulmonale
Pretibial and pedal oedema
Presacral oedema in bed ridden patients
Ansarca rarely (general swelling of whole body)
How can you differentiate between asthma and COPD if history and exam leaves uncertainty
Asthma will have a large response (over 400ml) to bronchodilators and oral steroids (COPD wont)
Serial peak flow measurements showing 20% or greater diurnal or day-to-day variability suggest asthma
Clinically significant COPD is not present if theFEV1and FEV1/FVCratio return to normal with drug therapy.
What are the clinical characteristics of chronic bronchitis
Patients may be obese
Frequent cough and spitting are typical
Use of accessory muscles of respiration is common though dyspnoea is milder
Coarse rhonchi and wheezing may be heard on auscultation
Patients may have signs of right heart failure (i.e. cor pulmonale), such as edema and cyanosis
Infections are common
What causes atopic asthma
Caused by a Th2 and IgE mediated response to environmental allergens
Characterized by an immediate phase and a late phase reaction
If the cor pulmonale is caused by CTEPH or PE what other treatment may be required
Anticoagulation
How might localised pulmonary haemorrhage appear on CXR/CT
hazy consolidation or ground glass infiltrates
What causes bronchiectasis
Congenital and hereditary conditions
Severe necrotizing pneumonia
Immune disorders
Bronchial obstruction Idiopathic - 50% of cases
Describe the pathogenesis of emphysema
Toxic injury and inflammation
Protease-antiprotease imbalance (e.g. increase in protease = more breakdown)
Oxidative stress - may enhance inflammatory response
List the causes of non-idiopathic interstitial pulmonary fibrosis
Occupational exposure (asbestosis, silicosis, etc.) Environmental antigens (farmer’s and pigeon-fancier lung, etc.) Drugs ± radiation Systemic illness (Hep C, HIV, IBD)
What is the aim of treatment in Group 2 PAH
Mainly involves treating the left-sided heart failure.
Which lung cancers could be classed as N0
Those with no metastasis to regional lymph nodes
The presence of mitoses means it is a malignancy - true or false
False
Can be seen in normal cells - e.g. dividing or hyperplastic
How might diffuse pulmonary haemorrhage appear on CXR
Often non-specific
May see bilateral air-space consolidation with apical sparing
What is the definition of neoplasia
New, uncontrolled growth of cells that is not under physiologic control
Describe the characteristics of non-specific interstitial pneumonia
Cellular and fibrosing pattern.
Fibrosis: diffuse/patchy interstitial fibrotic lesions of roughly the same age (important distinction from UIP)
No fibroblastic foci, honeycombing, hyaline membranes or granulomas
List the different types of idiopathic interstitial pneumonias
Idiopathic pulmonary fibrosis (IPF) - most common
Non-specific interstitial pneumonia (NSIP)
Cytogenic organising pneumonia (COP)
Acute interstitial pneumonia (AIP)
Desquamative interstitial pneumonia (DIP)
Respiratory bronchiolitis-associated interstitial pneumonia
Lymphoid interstitial pneumonia
Which factors affect the development of dust-borne diseases
Dust retention - how much stays in lungs
Particle size
Particle solubility and cytotoxicity
Particle uptake by EC or travel across the linings
Activation of the inflammatory system
Tobacco smoking
List potential complications of respiratory failure which are seen in the GI tract
Stress ulcers
Ileus
Haemorrhage
Gastric distension
Define type 2 respiratory failure
PaO2 < 8 kPa
PaCO2 > 6kPa
High CO2
List the potential mechanisms of death in cor pulmonale
CP can decompensate
Rarely can progress to LHF
Massive peripheral oedema can cause hypovolemic shock
Hypertrophied cardiac tissue may become ischemic which can lead to arrhythmias
Renal congestion can lead to azotemia (excess N)
CP can cause venous congestion and hypoxia in the CNS
Venous congestion and hypoxia in the CNS caused by CP can also be fatal
Massive PE that caused the CP can lead to obstructive shock
Complications of the underlying cause of CP can be fatal
All of the above can be fatal
Which fibrotic lung diseases come under the chronic category
Those resembling IPF and usually share a common pathology, e.g. UIP.
Many of the rheumatologic/CTDs, chronic HSP, radiation and drug-related pulmonary fibrosis, occupational exposures.
A malignant lesion on the R lung is approximately 4 cm across and is invading the main bronchus. Biopsies show involvement of the left hilar lymph nodes, and metastases have been found in the brain and spine. What is the correct staging using the TNM system?
T2 - Tumour 3-5cm and involving main bronchus
N3 - mets to contralateral hilar nodes
M1 - mets present
What is a fibrosarcoma
Malignant neoplasm of the connective tissues (fibrous tissues)
List examples of chronic interstitial and infiltrative disease
Pneumoconiosis
Interstitial fibrosis
DALDs
What name is given to a malignant neoplasm of the epithelial linings of ducts and glands
Adenocarcinoma
Give examples of vasodilator drugs
Endothelin receptor antagonists - ambrisentan)
PDE-5 inhibitors – tadalafil
Prostacyclin analogues or agonists – beraprost
What is restrictive lung disease
Refers to diseases which involve reduced expansion of lung parenchyma and result in a decreased lung capacity
What are the complications of CTEPH treatment
Aside from the typical risks of cardiothoracic surgery, there are 2 main complication that occur during thromboarterectomy:
Pulmonary artery seal – the redistribution of blood flow causes a severe V/Q mismatch
Reperfusion pulmonary oedema- fluid shift occurs in the surgical area
Also have the typical side effects of medications.
In COPD, when the emphysema is moderate or severe, what is the main mechanism of airflow limitation
The loss of elastic recoil caused by emphysema
Rather than the bronchiolar disease
Describe the macroscopic features of sarcoidosis seen in the lungs
No macroscopic changes except in advanced cases where granulomas join to form small nodules
These are palpable or visible as 1-2cm non-caseating, non-cavitated consolidations and are primarily distributed along lymphatics and around bronchi and blood vessels.
Which lung cancers could be classed as T2
Tumour 3-5cm OR Involvement of the visceral pleura or mainstem bronchus but not the carina OR Lobar atelectasis
Silicosis is rapidly fatal - true or false
False
It is a slow killer but significantly impaired lung function impacts QoL
What is the most common form of idiopathic interstitial pneumonia
Interstitial pulmonary fibrosis (IPF)
How do you manage Cryptogenic Organising Pneumonia (COP)
Some recover spontaneously
Most need oral steroids for 6m+ for complete recovery
Long-term prognosis depends on underlying disorder
Describe the typical clinical course of acute respiratory failure
Comes on quickly
Much more serious and life threatening than the chronic course
Can be managed at the time and resolve or leaves long term complications
List the potential surgical treatments for cor pulmonale
Venesection if hematocrit >65% in polycythemia
Pulmonary embolectomy in PE that’s haemodynamically unstable
Single/double lung and heart transplants in terminal stages in young patients
What happens when mast cells degranulate in atopic asthma
They produce cytokines and other mediators which induce induce the early phase hypersensitivity reaction and then eventually the late phase reaction
The mediators trigger the bronchoconstriction by stimulating the parasympathetic system
What determines the rate of growth of a tumour
Doubling time of tumor cells
Fraction of cells that have the ability to replicate
The rate at which tumor cells die and shed
Describe the histological features of small cell lung carcinoma
Poorly differentiated cells with little cytoplasm and ill-defined borders
What is the most common cause of acute onset cor pulmonale
Massive PE
What is the prognosis of cor pulmonale
50% deceased within 5 years
Prognosis depends on underlying cause with lung parenchymal disease having a worse prognosis
Describe the appearance of the plexiform lesions seen in pulmonary hypertension
Lesions have medial hypertrophy, eccentric or concentric laminar intimal proliferation and fibrosis, fibrinoid degeneration, and thrombotic lesions
List potential complications of tracheotomy
Haemorrhage
Recurrent laryngeal and vagus nerve damage
Pneumothorax
Obstruction of the airway from mucus and secretions or from scarring in healing
Collapse of the trachea
Which drugs can induce PAH in Group 1
e.g. subgroup 3
Aminorex, fenfluramine derivatives, and toxic rapeseed oil
Other risks included amphetamine, cocaine, St John’s wort
Which other diagnoses must be excluded when considering sarcoidosis
TB, fungal infections and berylliosis
All can also cause non-caseating granulomas
List the subdivisions of group 1 PAH
Group 1 - Pulmonary arterial hypertension - idiopathic
Group 2 - heritable PAH - caused by gene mutations included in BMPR2 and ALK2
Group 3 - drug or toxin induced
Group 4 - due to conditions which cause localised lesion in the arterioles
List the microscopic features of IPF
Patchy interstitial fibrosis which varies in intensity and age
Typical to see both early and late lesions at same time
Honeycomb fibrosis
Mild to moderate inflammation in the fibrotic areas - mostly lymphocytes, few plasma cells, neutrophils, eosinophils & mast cells
Foci of squamous metaplasia + SM hyperplasia may be present
May also have pulmonary arterial hypertensive changes
Diffuse alveolar damage in acute exacerbations
List some of the effects that asbestos has on the lungs
Localised fibrous plaque Pleural effusions (recurrent) Parenchymal interstitial fibrosis (asbestosis) Lung carcinoma Mesothelioma
Which left-sided heart diseases can cause Group 2 PAH
Systolic dysfunction Diastolic dysfunction Valvular defects Congenital or acquired inflow/outflow tract obstruction Congenital cardiomyopathies.
What are the symptoms of Acute interstitial Pneumonia (AIP)
Sudden onset dyspnoea
Rapid development of respiratory failure
Non-productive cough
Sarcoidosis lesions in the lungs have a tendency to heal - true or false
True
Often there is – varying stages of fibrosis and hyalinisation seen
Which other diseases does asbestosis increase your risk of
5-fold increase in lung cancer - it is a tumour initiator + promoter
If you also smoking = 55-fold increase in lung cancer
Toxic chemicals such as tobacco carcinogens can attach to the asbestos fibres and make them a more potent carcinogen
Radiographic imaging in patients with group 2 PAH may show what
Enlarged PA Ventricular dilatation Enlarged heart Oedema Dilated left atrium is a sign of chronic elevated left sided pressures
What percentage of lung cancers are caused by tobacco
70%-90% of all cases
How do you manage COPD
Provide with info and support
Assess and address smoking – nicotine replacement therapy
Vaccinations - Offer pneumococcal vaccination and an annual influenza
Develop an individualized exacerbation action plan
Pulmonary rehabilitation + chest physio
Inhaled and oral therapies
Describe the course of acute fibrotic lung diseases
Has a fulminant, progressive, remitting, or resolving course
Describe the pathogenesis of Group 2 PAH
Left sided pressures increase and causes backpressure in the pulmonary venous system
Persistent high pressures lead to structural and functional changes in the pulmonary vessels
This includes vasoconstriction which increases the mean pulmonary arterial pressure.
Right ventricular systolic pressure increases in order to maintain CO
In patients with type 1 respiratory failure, what concentration of O2 should be given as treatment
24-60% O2
What type of pleural effusion can be caused by asbestosis
Usually serous but can be bloody
Describe the pathological features of acute phase hypersentivity pneumonitis
Acute alveolar damage (1st hrs-days from exposure)
How can pulmonary haemorrhage lead to death
Repeated bleeds can lead onto organising pneumonia, collagen deposition in the vessels and eventually pulmonary fibrosis.
All of this disruption can be fatal
Haemorrhage related respiratory failure is a common cause of death
How might localised pulmonary haemorrhage appear on CXR/CT
hazy consolidation or ground glass infiltrates
How does squamous cell lung cancer present on radiographs
Asymptomatic and invisible
Which part of the tumour determines its growth and spread
The stroma
What are the main mechanisms behind type 2 respiratory failure
Type 2 is caused by alveolar hypoventilation with/without V/Q mismatch
Define each T stage in the TMN staging system (general cancer)
Tis - carcinoma in situ
T1 - Tumour ≤ 3cm
T1a – ≤ 1cm
T1b – 1-2cm
T1c – 2-3cm
T2 - Tumour 3-5cm
T3 - Tumour 5-7cm
T4 - Tumour > 7cm
List the diseases that cause diffuse alveolar filling that can be the underlying cause of respiratory failure
Cardiogenic and neurogenic oedema
Pneumonia
Extensive pulmonary haemorrhage
They all lead to inadequate gas exchange
List disorders of the peripheral nervous system, respiratory muscles and chest wall that can be the underlying cause of respiratory failure
Guilliane Barre syndrome Myasthenia gravis Muscular dystrophy Morbid obesity Kyphoscoliosis
They all cause inadequate ventilation causing hypoxia and hypercapnia
Tobacco smoking accounts for as much as 70% of COPD cases - true or false
False
Its as much as 90%
What can cause hypersensitivity pneumonitis
Exposure to inhaled organic antigens
Includes: bird fancier’s lung, farmer’s lung, etc.
List the macroscopic features of chronic bronchitis
Hyperemia
Swelling
Oedema of mucus membranes
Heavy casts of secretions and pus fill the bronchi and bronchioles
Which types of cancer can be caused by asbestos exposure
Lung carcinoma
Mesothelioma
Extra-pulmonary neoplasms such as laryngeal or ovarian
What are the clinical features of respiratory failure
They will have clinical features of the underlying cause (e.g. pneumonia > fever, cough, sputum etc.)
Dyspnoea is the common symptom
Will have features of hypoxia and hypercapnia (other card)
List diseases that can lead to Type 1 respiratory failure
COPD Pneumonia Asthma Pulmonary oedema Pulmonary fibrosis PE Pulmonary Hypertension ARDS
Many more
Describe the pathological features of chronic phase hypersentivity pneumonitis
Interstitial fibrosis with fibrocytic foci
Honeycombing
Obliterative bronchitis
Loosely-formed granulomas
Describe the pathogenesis behind IPF
It appears to be a primary disorder of fibroblast activation + proliferation in response to an unknown trigger
Genetic analyses point towards roles of deterioration of the alveolar epithelium due to telomere shortening, altered mucin production, and abnormal signaling in alveolar fibroblasts
Injury to alveolar epithelial cells triggers increased local production of fibrogenic cytokines
In which lung disease would you see weakly birefringent silicate particles
Silicosis
What is the most common type of PAH
Group 2
That caused by left heart disease
What are the clinical features of Group 3 PH
Patient will have the symptoms of the underlying lung disease alongside the typical PH symptoms
Again can go on to develop right-heart failure or cor-pulmonale and their associated symptoms
Which lung cancers could be classed as T3
Tumour 5-7cm
OR
Involvement of the parietal pleura, chest wall, diaphragm, phrenic nerve, mediastinal pleura or parietal pericardium OR
Separate tumour nodules in the same lobe
How does silicosis present
SOB only when progressive massive fibrosis
Describe the pathogenesis behind occupational lung diseases
Environmental trigger from occupational dusts etc.
However, only a small % of those exposed will develop the disease which implies there is also a genetic predisposition
Describe the epidemiology of pulmonary haemorrhage
Affects only 1 in 1000 live births
More common in premature or low birth weight babies
Describe the presentation of subacute fibrotic lung diseases
Presentations with a variable course are typified by COP (weeks/months of prodromal flu symptoms; SOB + exercise intolerance).
Can recur when steroids are withdrawn/tapered
What is the definition of pulmonary hypertension
Mean pulmonary arterial pressure of over 25mmHg at rest or over 30mmHg during exercise.
Will also have a capillary wedge pressure of <15mmHg.
Where are normal mitoses seen in the body
Seen in normal tissues exhibiting rapid turnover e.g. epithelial lining of gut
Also seen in non-neoplastic proliferations like hyperplasia’s
How does ILD lead to Group 3 PH
Chronic injury to the alveolar membranes and fibrosis with vascular remodelling
What are the clinical features of Group 2 PAH
Symptoms can be non-specific but are usually progressive
Similar symptoms to group 1 but group 2 patients generally have increased dyspnea, lower exercise tolerance and shorter survival
Again, it can progress to RHF (and therefore develop the common symptoms)
What is lepidic adenocarcinoma also known as
Bronchoalveolar carcinoma
That’s the old name
How do you treat small cell lung carcinoma
Limited disease is sensitive to chemotherapy and radiotherapy but 5-year survival is only 10%
List common symptoms of sarcoidosis
Insidious SOB Cough Chest pain Haemoptysis Constitutional symptoms Skin changes e.g., erythema nodosum, or uveitis might also suggest sarcoid
What causes the pathological findings in cor pulmonale
The right-heart failure
Systemic and portal venous congestion due to backpressure
May have some findings from the underlying lung disease
What is the only definitive therapy for IPF
Lung transplantation
List the microscopic features of bronchiectasis
Inflammatory exudation within bronchi and bronchiole wall associated with desquamation of lining epithelium and extensive ulceration, bacteria found too
List the macroscopic features of Group 2 PAH
Thickening of the capillary endothelial basement membrane
Narrowing of the pulmonary arteries
Smooth muscle hypertrophy (as a result of elastin production)
Stiffening of the pulmonary vessels
Define each T stage in the TMN staging system (general cancer)
Tis - carcinoma in situ
T1 - Tumour ≤ 3cm
T1a – ≤ 1cm
T1b – 1-2cm
T1c – 2-3cm
T2 - Tumour 3-5cm
T3 - Tumour 5-7cm
T4 - Tumour > 7cm
List diseases that can lead to Type 2 respiratory failure
COPD Severe asthma Drug overdose Poisoning Myasthenia gravis Polyneuropathy
Many more
Describe the presentation of acute fibrotic lung diseases
Can present without PMH of lung disease or be part of an accelerated phase of underlying interstitial disease; most rapidly progress to respiratory failure.
List the common complications of COPD
Respiratory infections - higher risk of catching them and also more vulnerable to further lung damage
Heart problems - increases risk of heart disease, including heart attack
Lung cancer - increased risk
High blood pressure in lung arteries
Depression
How can O2 therapy be administered
Nasal cannula Face mask Non rebreather mask BiPAP/CPAP Intubation Tracheotomy
In acute cases it is given at the time, as required but in chronic cases they may have it long term
Describe the features of simple coal worker’s pneumoconiosis
Coal macules (1-2mm d.) consist of C-laden macrophages scattered throughout lung, upper lobes & upper zones of lower lobes in particular.
Occurs next to respiratory bronchioles since this is site of initial dust accumulation
What causes the cough seen in lung cancer
Central airway involvement
Describe the prevalence of intrinsic lung diseases
Overall prevalence of 3-6 cases/100,000 people (US)
Idiopathic pulmonary fibrosis (IPF) prevalence in UK is 50/100,000
Highest prevalence in adults >75 years old.
M>F
The surgical treatments for cor pulmonale can have what complications
Venesection – nerve damage
Pulmonary embolectomy – thrombosis and dissection
Heart transplant – rejection, primary graft failure, cardiac allograft vasculopathy
Lung transplant – rejection, bronchiolitis obliterans syndrome, post transplantation lymphoproliferative disorder
What is Lambert-Eaton Syndrome
Muscle weakness due to autoimmune targeting of the neuromuscular junction
How does cor pulmonale progress
It is a chronically progressive condition
Patients have the features of the underlying lung disease before slowly progressing to CP
Some cases such as those due to large PE can be acute and then acutely deteriorate into chronic CP
What are the clinical features of bronchiectasis
Coughing up yellow or green mucus daily
Shortness of breath that gets worse during flare-ups
Fatigue
Fevers and/or chills,
Wheezing or whistling sound while you breathe
Coughing up blood or mucus mixed with blood
Chest pain from increased effort to breath
Clubbing
What are the 3 classic symptoms of pulmonary haemorrhage?
Dyspnoea, haemoptysis, iron deficiency anaemia
List the characteristics of a malignant tumour
Harmful - includes cancer and often fatal
Not localized
Can invade and destroy adjacent structures and spread to distant sites (metastasize)
Tend to adhere to any part that they seize on in an obstinate manner
Typically have poorly defined margins and are less well-differentiated
Describe the pathogenesis behind occupational lung diseases
Environmental trigger from occupational dusts etc.
However, only a small % of those exposed will develop the disease which implies there is also a genetic predisposition
How can you manage hypersensitivity pneumonitis
Antigen avoidance
Recognise the antigen and reduce exposure to it
What causes coal workers lung
Inhalation of coal particles and other admixed forms of dust
Carbon dust is main culprit
How does silicosis appear on polarised microscopy
Nodules show weakly birefringent silicate particles
What happens to the nucleus:cytoplasm ratio in malignancy
It approaches 1:1 instead of 1:4 to 1:6
Nucleus gets larger
Describe status asthmaticus
- Persistent asthma attack basically
It is an exhausting process as huge respiratory effort is required (muscles tire fast)
Unless you provide treatment (ventilation to reduce effort) it can be quickly fatal
Quickly become hypoxic and can cause death (also high risk of arrhythmia)
What is the function of O2 therapy in respiratory failure
To ensure adequate ventilation
To reduce hypoxia
To correct respiratory acidosis
In patients with type 2 respiratory failure, what concentration of O2 should be given as treatment
Start at 24% and monitor CO2 levels
How do you diagnose pulmonary haemorrhage
Bloods - FBC, coagulation studies, serology
Radiography
Bronchoscopy - assess bleeding site
Lung biopsy - carried out if the less invasive tests cannot find a cause
Further tests may be carried out if a specific cause is suspected
Which other diseases does silicosis increase your risk of
TB - inhibits macrophages from killing phagocytised mycobacterium
2-fold increased risk of lung cancer.
What is the FVC
The total amount of air exhaled forcefully and quickly after inhaling as much as you can
Which lung cancers could be classed as N1
Those with metastasis to ipsilateral intraparenchymal, parabronchial or hilar lymph nodes
Name a drug which can cause drug induced asthma
Aspirin
The characteristics of usual interstitial pneumonia are seen in which diseases
IPF
Connective tissue disorders
Chronic hypersensitivity pneumonia
Asbestosis
Must distinguish from each other with clinical, laboratory and histological findings
What does papillary lung adenocarcinoma look like
Finger like
Describe the abnormal nuclear morphology seen in malignancy
Variable and often irregular nuclear shape
Cancer cells: N:C ratio may approach 1:1 instead of 1:4 to 1:6
Chromatin is often seen
Nuclei may be abnormally large
What is the other name for Cryptogenic Organising Pneumonia (COP)
Bronchiolitis obliterans organising pneumonia (BOOP)
Is there a genetic component to asthma
Yes - many polymorphisms involved
Generally involves mutations in genes for different mediators
Can type 1 respiratory failure become type 2
Yes
And vice versa
Patients can also move in and out of respiratory failure
Describe the pathogenesis of Group 4 PH (CTEPH)
Clots form where the initial PE was and adhere to the vessel walls (mostly in large or medium arteries).
This causes stenosis and occlusion of the artery.
Blood is diverted through other vessels and as a result their pressure increases.
These vessels may then constrict and end up undergoing remodelling.
Microvascular thrombi may also form.
This all leads to a further increase in pressure and a progression of the disease (RHF).
How do you treat lung adenocarcinoma
Surgery, radiotherapy, chemotherapy
Responds well to immunological treatment if mutations in EGF-receptors are present
How do you diagnose group 3 PH
Diagnostic tests are the same as all other groups
Extra tests may be performed to confirm the underlying cause
E.g. Pulmonary function for COPD or ILD and polysomnography for OSA
How does coal worker’s pneumoconiosis present
Usually benign
Little change to lung function even in severe cases
What is a neoplasm
The collection of cells and stroma composing new growths
What name is given to a benign neoplasm of the stratified squamous epithelium
Squamous cell papilloma
What is the common outcome of all types of PH? (i.e. what does it progress to?)
Right-heart failure
What may you find in the sputum sample of a patient with squamous cell lung cancer
Atypical cells may be found on sputum cytology
How do you manage pulmonary artery seal and reperfusion pulmonary oedema which can be seen after CTEPH treatment
Supportive treatment – O2, ventilation and NO
Signs and symptoms of cor pulmonale present early in the disease - true or false
False
Symptoms of CP tend only to occur in advanced stages
This is an issue if the underlying lung disease also has few symptoms - late diagnosis
What can cause Cryptogenic Organising Pneumonia (COP)
It is a response to infection/inflammatory injury of lungs
Seen in transplant rejection
How does sleep disordered breathing lead to Group 3 PH
Multifactorial - includes hypoxic vasoconstriction, hyperinflated lungs
Related to the severity and duration of apnoea’s as these episodes increase PA pressure
How does PH affect survival in lung disease patients
Having PH alongside the underlying lung disease can reduce survival. For example, 5-year survival COPD patients without pulmonary hypertension is 62%, compared with 36% in those with both
List the cytologic features of a benign neoplasia
Low nuclear to cytoplasmic ratio Contain regular cells Normochromatic nuclei Absent or scanty mitotic figures Only mild architectural disturbance with maintained polarity
How can asbestosis cause pulmonary hypertension and cor pulmonale
Scarring can trap & narrow pulmonary arteries and arterioles
Increases pressure
List the potential medical treatments for diffuse parenchymal lung diseases (DPLDs)
Smoking cessation and good pulmonary hygiene
Supplementary O2 for significant hypoxaemia
Removal of exposure if indicated – e.g., occupational, HSP.
Stop toxic medications
Treat respiratory infections
Pulmonary rehabilitation may improve exercise intolerance and QoL.
Influenza and pneumococcal vaccinations encouraged.
List the clinical features of CTEPH
Exercise intolerance
Fatigue
Progressive dyspnoea
As pressure increases symptoms progress to:
Chest discomfort
Syncope
Haemoptysis
Oedema (and other symptoms of heart failure )
Describe the course of chronic fibrotic lung diseases
Insidious and slowly progressive
What can cause localised pulmonary haemorrhage
Secondary aspiration of blood following infection, tumours, bronchitis or bronchiectasis
Infarction
Infection (pneumonia, TB etc)
Trauma (laceration or contusion)
Pulmonary arteriovenous malformation or other congenital malforamtions
Underlying weakness in the vessels
Iatrogenic – e.g. following biopsy
Which has the better prognosis usual interstitial pneumonia or non-specific interstitial pneumonia
Non-specific interstitial pneumonia
What causes the chest pain seen in lung cancer
Extension into other thoracic structures
List the diseases that cause severe airway obstruction that can be the underlying cause of respiratory failure
Epiglottitis Tumours of the trachea COPD Asthma CF
They can all cause hypoxia and hypercapnia
Describe the structure of tumour giant cells
A single huge polymorphic nucleus/two or more large hyperchromatic nuclei
Sarcoidosis is a diagnosis of exclusion - true or false
True
Huge variety of symptoms that can mimic other conditions
What does acinar lung adenocarcinoma look like
Cuboidal or columnar epithelium
What is bronchiectasis
A disorder where there is destruction of the smooth muscle and elastic tissue by inflammation stemming from persistent or severe infections
This leads to permanent dilatation of bronchi and bronchioles
How do you determine if the respiratory failure is acute or chronic
Determine the underlying cause and symptom presentation
Not ABGs
List the main inflammatory cells involved in atopic asthma
Eosinophils
Mast cells
Neutrophils
T lymphocytes
List the common features of hypercapnia
Headache Peripheral vasoconstriction Tachycardia Bounding pulse Tremor/flap Papilloedema Drowsiness and confusion
List the main mediators of atopic asthma
Th2 cytokines
IL-4, IL-5 and IL-13
Respiratory failure is purely a chronic condition – true or false
False
It can have a chronic onset and course but can also have an acute onset and short duration
It all depends on the underlying cause
Which diseases (general categories) can cause respiratory failure
Diseases that cause diffuse alveolar filling
Severe airway obstruction
Disorders of the peripheral nervous system, respiratory muscles and chest wall - causes inadequate ventilation
Depression of the neural drive of respiration - drugs, structural changes or metabolic abnormalities
List common complications of asthma
Growth delay and higher risk of learning difficulty in children Permanent narrowing of airways Medication side effects Higher risk of obesity Risk of A&E visits - asthma attacks Lingering cough Frequent sick days Higher risk of depression
