Lung Pathology Flashcards
What can asthma be described as?
paroxysmal contraction of the airways resulting in decreased airflow due to reversible airway obstruction over a period of time
What are the two types pf asthma?
Extrinsic = asthma more common in children and associated with exposure to external agents e.g pollen, chemicals, drugs, aspergillus
Intrinsic = asthma more common in adults - exercise, infection and stress
What is the pathophysiology of asthma?
various allergens bind to IgE attached to certain immune cells (eosinophils) leading to degranulation
Charcot-Leyden crystals may be seen
What are charcot leyden crystals?
microscopic crystals found in people with allergic diseases such as asthma
- protein that interacts with eosinophil lysophospholipases which act on biological membranes to regulate the multifunctional lysophospholipids
protein may possess IgE binding or carbohydrate binding activities
crystal can be found in sputum
What does the chronic inflammation in asthma cause?
in the conducting zone of the airways it leads to increased bronchial gland mass with increased mucus leading to the formation of curschmann’s spirals = microscopic findings in the sputum
spiral shaped mucus plugs from sub epithelial mucous gland ducts or bronchioles
may also be increased smooth muscle
What white cells are involved in inflammation of the bronchial mucosa?
T lymphocytes, eosinophils, potentially neutrophils
- t lymphocytes are important in the regulation of airway inflammation through the release of numerous cytokines
What other changes occur in the bronchioles in asthma?
shedding of bronchial epithelial cells (potentially due to failure of intercellular adhesion mechanisms) as well as thickening of epithelial basement membrane
What are adhesion molecules important for in asthma?
selecting and interns - critical in directing the inflammatory changes in the airways
What do cell-derived mediators do in asthma?
influence smooth muscle tone and produce structural changes in remodeling of the airway
What is the airway hyper responsiveness and bronchial hyper-reactivity in asthma due to?
an exaggerated response to numerous exogenous and endogenous stimuli
- mechanisms involved include direct stimulation of the airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator secreting cells such as mast cells or sensory neurons
degree of hyper-responsiveness correlates well with severity
What is status asthmatics a response to?
response to asphyxia - where one asthma attack follows another without pause
What are the features of status asthmatics ?
hyperinflation of the airways and petechial hemorrhages
- petechial = small (1-2mm) red or purple spot on the skin caused by a minor bleed from broken capillary - occurs due to asphyxiation
- also mucoid plugging of large and small airways and atelectasis
What is atelectasis?
collapse or closure of a lung resulting in reduced or absent gas exchange
- may affect part or all of the lung and is usually unilateral
- alveoli are deflated down to little or no volume
- it is the mucoid plugs that lead to reduced gas exchange which then leads to atelectasis
What are the main symptoms of COPD?
SOB, cough with sputum production
What are blue bloaters?
person where the primary underlying lung pathology is chronic bronchitis - caused by excessive mucus production with airway obstruction resulting in goblet cell metaplasia and chronic inflammation round bronchi = increased mass of bronchial mucus glands (reid index >0.4)
How does the body respond in chronic bronchitis to the increased obstruction?
by decreasing ventilation and increasing cardiac output - poor ventilation to perfusion mismatch leading to hypoxemia and polycythemia
also have hypercapnia
What happens in chronic bronchitis in terms of the increasing obstruction?
residual lung volume gradually increases (“bloating part”)
- bluish lips and faces
What is the clinical definition of chronic bronchitis?
persistent cough with sputum production for at least 3 months over the past 2 consecutive years
What are the main causes of chronic bronchitis?
tobacco smoking and atmospheric pollution
What are the pathological changes in the large airways that occur in chronic bronchitis?
increase in submucosal gland mass (reid index>0.4)
increase in numbers of goblet cells
increase in smooth muscle
chronic inflammatory cell infiltrate of lamina propria
What is the reid index ?
measure of mucus gland thickness in comparison to the thickness of the basement membrane
What is the difference between the diagnosis of chronic bronchitis and emphysema?
chronic bronchitis = clinical diagnosis
Emphysema = pathological/morphological diagnosis = pink puffers
What is emphysema?
destruction of the airways distal to the terminal bronchiole
What happens in emphysema?
digestion of elastin in the alveolar walls leads to dilation of the air spaces = less surface area for gas exchange
gradual destruction of the pulmonary capillary bed and thus decreased ability to oxygenate the blood = less vascular bed for gas exchange
Do blue bloaters or pink puffers have less ventilation-perfusion mismatch?
less ventilation-perfusion mismatch in pink puffers
How does the body compensate in emphysema?
hyperventilation (puffer part) - keeps ABG normal
What eventually occurs in emphysema patients due to the hyperventilation?
due to the low cardiac output people develop muscle wasting and weight loss
Do blue bloaters or pink puffers have less hypoxaemia?
pink puffers have less hypoxemia compared to blue bloaters and this is why they appear pink
What is emphysema described as?
abnormal permanent enlargement of air spaces distal to the terminal bronchiole accompanied by destruction of their walls without obvious fibrosis
may be small amounts of fibrosis from the immune response
What is a primary pulmonary lobule?
lung unit distal to the respiratory bronchiole - significantly smaller than an acinus and composed of alveolar ducts, alveolar sacs and alveoli
What is secondary lobule formed of?
about 30-50 primary lobules
secondary is about 1-2.5cm across
polyhedral shaped bounded by fibrous septa
What is each secondary pulmonary lobule supplied by?
lobular bronchiole and a pulmonary artery branch
drained by pulmonary veins - form in periphery of the lobule and pass through the interlobular septa
What are the morphological types of emphysema?
centri-lobular - 75%
panacinar
paraseptal
irregular emphysema - associated with scarring and is clinically not significant
What is centri-lobular emphysema?
generally caused by smoking - primarily affects upper lung lobes
- involves preferentially the centre of the acinus around the terminal bronchiole and is most severe in the upper lobes
What is panacinar emphysema?
associated with alpha-1 antitrypsin deficiency - involves all the lung fields, particularly the bases
What is paraseptal emphysema?
distal acing - cause of this is unclear but it could be a cause of spontaneous pneumothorax
What is meant by compensatory emphysema?
one portion of the lung increases in size and function when another portion is destroyed or temporarily useless
occurs in pneumonias, pleural effusions and pneumothorax
What are these different types of emphysema caused by?
- senile
- obstructive
- bulls
- interstitial
senile = associated with aging lung
obstructive = caused by a tumor
bullous=associated with bullae often with background of centrilobular emphysema
interstitial = air in the connective tissue of the lung, pleura or mediating
What are the complications of COPD?
Cor pulmonale - pulmonary vascular remodeling is main cause of increase in pulmonary artery pressure = hypoxia, inflammation and loss of capillaries in severe emphysema = lead to pulmonary hypertension, increase RH after load and causing R HF
respiratory failure
polycythemia
lung cancer
pneumothorax - ruptured bullae can burst and leak air into pleura if there is coexistent emphysema
What is interstitial pulmonary fibrosis characterized by?
progressive interstitial scarring, leading to respiratory incapacity and effacement of the lung architecture which in extreme cases may result in a honeycomb pattern
What is meant by honeycomb lung?
presence of cysts several mm to a cm in diameter in the background of dense fibrous scarring
scarring is much worse than seen in emphysema
honeycomb structure is most prominent in the sub pleural parenchyma
What is meant by reticular interstitial pattern?
refers to a complex network of opacities that usually involve the lung diffusely
medium sized reticular patterns = honeycombing
What are the causes of honeycomb lung cancer?
- previous lung diseases (interstitial pneumonia, diffuse alveolar damage)
- inorganic dust exposure (asbestosis)
- interstitial granulomatous diseases (infections, hypersensitivity pneumonia, sarcoidosis - lead to formation of granulomas in the interstitium)
- histiocytosis X
What is histiocytosis?
group of clinical syndromes characterized by an abnormal proliferation of histiocytes
these diseases are related to other forms of abnormal proliferation of WCC e.g. leukemia’s and lymphomas
How is interstitial fibrosing alveolitis diagnosed?
also known as interstitial pulmonary fibrosis = type of ILD
- either be idiopathic or diagnosed by exclusion and has an incidence of 3-5/100,000
What can interstitial fibrosing alveolitis be secondary to?
connective tissue diseases dust and smoke inhalation asbestos EAA, sarcoidosis Shock lung, radiation drugs
What is interstitial pulmonary fibrosis ?
inflammatory condition of the lung affecting primarily the alveoli - typical symptoms: productive or drug cough, chest pain, feel and trouble breathing
What is pneumonia?
usually caused by an infection with viruses or bacteria and less commonly other organisms
can also get non-infection pneumonia
What signs are present in acute interstitial pneumonia?
signs of URTI
- then causes progressive rapid respiratory failure and has high mortality
How is acute interstitial pneumonia characterized histologically?
diffuse alveolar damage - comprises 3 stages:
- acute exudative phase = necrosis occurs here
- subsequent organising phase (hyaline membranes seen)
- final fibrotic phase
What is an exudate?
any fluid that filters form the circulatory systems into lesions or areas of inflammation
can be pus like or clear
fluid composed of serum, fibrin and WBC
caused by increase in vessel permeability whereas transudate is where there is an increase in pressure forcing fluid out of the vessel
How does usual interstitial pneumonia present?
insidious onset of dyspnoea and occurs in adults between 40-70
progressive downhill course with median survival of 4-5 years
What can usual interstitial pneumonia be associated with
seen with cryptogenic fibrosis alveolitis but also associated with collagen vascular diseases e.g. RA and scleroderma
What is the pathology of UIP?
heterogenous and there is non-uniform inflammatory and fibrosing process
typical biopsy there are areas of normal lung alternating with interstitial fibrosis and honeycombing - don’t biopsy honeycomb as there will be no tissue to test
What is desquamative interstitial pneumonia?
uncommon and occurs in middle aged smokers
presents with dyspnoea and a cough
increased macrophages in alveolar spaces and uniform interstitial fibrosis
collagen tends to form around the airways
How is desquamative interstitial pneumonia treated?
responds to steroid treatment and has relatively good prognosis
thought to be related to bronchiolitis
What is non-specific interstitial pneumonia?
presents as dyspnoea and cough in middle aged adults
may be underlying connective tissue disease in some
steroid responsive in most
uniform interstitial inflammatory and fibrosing process
What is extrinsic allergic alveolitis (EAA)?
hypersensitivity pneumonitis
- type 3 reaction (arthus reactions)
immune complexes between circulating antigen and IgG causes damage
wide range of antigens implicated e.g. drugs
How does EAA acutely present?
follows exposure to large amounts of antigen - sudden onset of dyspnoea, fever and chills
symptoms subside following cessation of exposure
How does a chronic case of EAA present?
prolonged exposure to small amounts of antigens
- insidious onset of dyspnoea, dry cough and fatigue
What is seen on CXR of chronic EAA?
Reticulonodular infiltrates- can progress to irreversible lung damage if exposure persists
Also see lower lobe ground glass and fine nodular densities
What can be seen histologically in EAA?
Variable lymphoplasmacellular infiltrate centred on small airways and alveolar ducts
small non-necrotising loose granulomas and foamy macrophages
BOOP like pattern in 50% cases
What 4 factors are commonly seen histologically in hypersensitivity pneumonitis?
1) cellular bronchiolitis - chronic inflammatory cells lining small airways (sometime with epithelial ulceration)
2) diffuse chronic interstitial inflammatory infiltrates - primarily lymphocytes and plasma cells
3) poorly circumscribed interstitial non-necrotising (non-caveating) granuloma - consisting of lymphocytes, plasma cells and epithelioid histiocytes with/out giant cells
4) individual giant cells in the alveoli or interstitial
