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
