Lung Pathology

Question 1

What can asthma be described as?

Answer 1

paroxysmal contraction of the airways resulting in decreased airflow due to reversible airway obstruction over a period of time

Question 2

What are the two types pf asthma?

Answer 2

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

Question 3

What is the pathophysiology of asthma?

Answer 3

various allergens bind to IgE attached to certain immune cells (eosinophils) leading to degranulation
Charcot-Leyden crystals may be seen

Question 4

What are charcot leyden crystals?

Answer 4

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

Question 5

What does the chronic inflammation in asthma cause?

Answer 5

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

Question 6

What white cells are involved in inflammation of the bronchial mucosa?

Answer 6

T lymphocytes, eosinophils, potentially neutrophils

- t lymphocytes are important in the regulation of airway inflammation through the release of numerous cytokines

Question 7

What other changes occur in the bronchioles in asthma?

Answer 7

shedding of bronchial epithelial cells (potentially due to failure of intercellular adhesion mechanisms) as well as thickening of epithelial basement membrane

Question 8

What are adhesion molecules important for in asthma?

Answer 8

selecting and interns - critical in directing the inflammatory changes in the airways

Question 9

What do cell-derived mediators do in asthma?

Answer 9

influence smooth muscle tone and produce structural changes in remodeling of the airway

Question 10

What is the airway hyper responsiveness and bronchial hyper-reactivity in asthma due to?

Answer 10

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

Question 11

What is status asthmatics a response to?

Answer 11

response to asphyxia - where one asthma attack follows another without pause

Question 12

What are the features of status asthmatics ?

Answer 12

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

Question 13

What is atelectasis?

Answer 13

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

Question 14

What are the main symptoms of COPD?

Answer 14

SOB, cough with sputum production

Question 15

What are blue bloaters?

Answer 15

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)

Question 16

How does the body respond in chronic bronchitis to the increased obstruction?

Answer 16

by decreasing ventilation and increasing cardiac output - poor ventilation to perfusion mismatch leading to hypoxemia and polycythemia
also have hypercapnia

Question 17

What happens in chronic bronchitis in terms of the increasing obstruction?

Answer 17

residual lung volume gradually increases (“bloating part”)

- bluish lips and faces

Question 18

What is the clinical definition of chronic bronchitis?

Answer 18

persistent cough with sputum production for at least 3 months over the past 2 consecutive years

Question 19

What are the main causes of chronic bronchitis?

Answer 19

tobacco smoking and atmospheric pollution

Question 20

What are the pathological changes in the large airways that occur in chronic bronchitis?

Answer 20

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

Question 21

What is the reid index ?

Answer 21

measure of mucus gland thickness in comparison to the thickness of the basement membrane

Question 22

What is the difference between the diagnosis of chronic bronchitis and emphysema?

Answer 22

chronic bronchitis = clinical diagnosis

Emphysema = pathological/morphological diagnosis = pink puffers

Question 23

What is emphysema?

Answer 23

destruction of the airways distal to the terminal bronchiole

Question 24

What happens in emphysema?

Answer 24

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

Question 25

Do blue bloaters or pink puffers have less ventilation-perfusion mismatch?

Answer 25

less ventilation-perfusion mismatch in pink puffers

Question 26

How does the body compensate in emphysema?

Answer 26

hyperventilation (puffer part) - keeps ABG normal

Question 27

What eventually occurs in emphysema patients due to the hyperventilation?

Answer 27

due to the low cardiac output people develop muscle wasting and weight loss

Question 28

Do blue bloaters or pink puffers have less hypoxaemia?

Answer 28

pink puffers have less hypoxemia compared to blue bloaters and this is why they appear pink

Question 29

What is emphysema described as?

Answer 29

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

Question 30

What is a primary pulmonary lobule?

Answer 30

lung unit distal to the respiratory bronchiole - significantly smaller than an acinus and composed of alveolar ducts, alveolar sacs and alveoli

Question 31

What is secondary lobule formed of?

Answer 31

about 30-50 primary lobules secondary is about 1-2.5cm across polyhedral shaped bounded by fibrous septa

Question 32

What is each secondary pulmonary lobule supplied by?

Answer 32

lobular bronchiole and a pulmonary artery branch | drained by pulmonary veins - form in periphery of the lobule and pass through the interlobular septa

Question 33

What are the morphological types of emphysema?

Answer 33

centri-lobular - 75% panacinar paraseptal irregular emphysema - associated with scarring and is clinically not significant

Question 34

What is centri-lobular emphysema?

Answer 34

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

Question 35

What is panacinar emphysema?

Answer 35

associated with alpha-1 antitrypsin deficiency - involves all the lung fields, particularly the bases

Question 36

What is paraseptal emphysema?

Answer 36

distal acing - cause of this is unclear but it could be a cause of spontaneous pneumothorax

Question 37

What is meant by compensatory emphysema?

Answer 37

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

Question 38

What are these different types of emphysema caused by? - senile - obstructive - bulls - interstitial

Answer 38

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

Question 39

What are the complications of COPD?

Answer 39

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

Question 40

What is interstitial pulmonary fibrosis characterized by?

Answer 40

progressive interstitial scarring, leading to respiratory incapacity and effacement of the lung architecture which in extreme cases may result in a honeycomb pattern

Question 41

What is meant by honeycomb lung?

Answer 41

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

Question 42

What is meant by reticular interstitial pattern?

Answer 42

refers to a complex network of opacities that usually involve the lung diffusely medium sized reticular patterns = honeycombing

Question 43

What are the causes of honeycomb lung cancer?

Answer 43

- 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

Question 44

What is histiocytosis?

Answer 44

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

Question 45

How is interstitial fibrosing alveolitis diagnosed?

Answer 45

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

Question 46

What can interstitial fibrosing alveolitis be secondary to?

Answer 46

``` connective tissue diseases dust and smoke inhalation asbestos EAA, sarcoidosis Shock lung, radiation drugs ```

Question 47

What is interstitial pulmonary fibrosis ?

Answer 47

inflammatory condition of the lung affecting primarily the alveoli - typical symptoms: productive or drug cough, chest pain, feel and trouble breathing

Question 48

What is pneumonia?

Answer 48

usually caused by an infection with viruses or bacteria and less commonly other organisms can also get non-infection pneumonia

Question 49

What signs are present in acute interstitial pneumonia?

Answer 49

signs of URTI | - then causes progressive rapid respiratory failure and has high mortality

Question 50

How is acute interstitial pneumonia characterized histologically?

Answer 50

diffuse alveolar damage - comprises 3 stages: - acute exudative phase = necrosis occurs here - subsequent organising phase (hyaline membranes seen) - final fibrotic phase

Question 51

What is an exudate?

Answer 51

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

Question 52

How does usual interstitial pneumonia present?

Answer 52

insidious onset of dyspnoea and occurs in adults between 40-70 progressive downhill course with median survival of 4-5 years

Question 53

What can usual interstitial pneumonia be associated with

Answer 53

seen with cryptogenic fibrosis alveolitis but also associated with collagen vascular diseases e.g. RA and scleroderma

Question 54

What is the pathology of UIP?

Answer 54

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

Question 55

What is desquamative interstitial pneumonia?

Answer 55

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

Question 56

How is desquamative interstitial pneumonia treated?

Answer 56

responds to steroid treatment and has relatively good prognosis thought to be related to bronchiolitis

Question 57

What is non-specific interstitial pneumonia?

Answer 57

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

Question 58

What is extrinsic allergic alveolitis (EAA)?

Answer 58

hypersensitivity pneumonitis - type 3 reaction (arthus reactions) immune complexes between circulating antigen and IgG causes damage wide range of antigens implicated e.g. drugs

Question 59

How does EAA acutely present?

Answer 59

follows exposure to large amounts of antigen - sudden onset of dyspnoea, fever and chills symptoms subside following cessation of exposure

Question 60

How does a chronic case of EAA present?

Answer 60

prolonged exposure to small amounts of antigens | - insidious onset of dyspnoea, dry cough and fatigue

Question 61

What is seen on CXR of chronic EAA?

Answer 61

Reticulonodular infiltrates- can progress to irreversible lung damage if exposure persists Also see lower lobe ground glass and fine nodular densities

Question 62

What can be seen histologically in EAA?

Answer 62

Variable lymphoplasmacellular infiltrate centred on small airways and alveolar ducts small non-necrotising loose granulomas and foamy macrophages BOOP like pattern in 50% cases

Question 63

What 4 factors are commonly seen histologically in hypersensitivity pneumonitis?

Answer 63

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