Week 14 Pathology - Lungs I

Question 1

What is atelectasis?

Answer 1

Loss of lung volume due to inadequate expansion of air space

Question 2

How does atelectasis cause hypoxia?

Answer 2

Results in shunting of inadequately oxygenated blood from pulmonary arteries into pulmonary veins, leading to ventilation/perfusion mismatch and hypoxia

Question 3

What are the 3 types of atelectasis?

Answer 3

1. Resorption
2. Compression
3. Contraction

Question 4

What is resorption atelectasis?

Answer 4

Obstruction prevents air from reaching distal airways, caused by mucus plug or FB, typically affecting post op patients, asthma, bronchiectasis, tumour

Question 5

What is compression atelectasis?

Answer 5

due to accumulation of fluid, blood, air within pleural cavity –> mechanical collapse

causes include pleural effusion, PTX, ascites

Question 6

What is contraction atelectasis?

Answer 6

Local or generalised fibrotic changes in lung/pleura hamper expansion and increase elastic recoil in expiration (i.e. ILD)

Question 7

Define asthma:

Answer 7

Chronic inflammatory airway disorder, characterised by
1. intermittent, reversible airway obstruction
2. chronic bronchial inflammation with eosinophils
3. Bronchial smooth muscle hypertrophy and hyperactivity
4. Increased mucous secretion

Question 8

What T helper cell phenotype is largely responsible for asthma?

Answer 8

Th2 response - exaggerated greatly in atopic asthma patients.

Question 9

What are the cytokines responsible, and their effects?

**Think letters of the alphabet

Answer 9

IL-4 = stimulation of IgE production
IL-5 = activates eosinophils (E = 5th letter alphabet)
IL-13 = stimulates mucous production and promotes IgE production by MAST cells (M = 13th letter of the alphabet)

Question 10

What is the brief pathophysiology of asthma attack?

Answer 10

IgE coats submucosal mast cells, which degranulate with cross linking of allergen, releasing granule contents, causing:

Early phase: bronchoconstriction, increased mucous production

Late phase: inflammation, activation of eosinophils, neutrophils and T cells, and epithelial cells activated to secrete cytokines that attract Th2 cells

Question 11

What is airway remodelling, and how does it relate to asthma?

Answer 11

Repeat episodes of inflammation cause remodelling, largely hypertrophy of bronchial smooth muscle and mucus glands, increased vascularity and deposition of sub endothelial collagen (fibrosis)

Question 12

How can you classify asthma?

Answer 12

Atopic: most common, Type I hypersensitivity, usually environmental antigens (dusts, pollens, dander)

Non-atopic: usually viral infection induced/air pollutants, lowered threshold of sub epithelial vagal receptors to irritants (muscarinic mediated)

Drug induced: NSAIDs

Occupational: exposures to chemicals/fumes/dusts

Question 13

What are some histological findings of chronic asthma?

Answer 13

Mucous plugging of bronchi/bronchioles (Curschmann spirals)
Charcot-Leyden crystals (eosinophils proteins condensed)
Thickened airway walls
Sub-basement membrane fibrosis
Increased vascularity of submucosa
Increase size and number of goblet cells and mucous secreting glands
Hypertrophy and hyperplasia of bronchial smooth muscle

Question 14

What is the major difference in definition of COPD?

Answer 14

Much the same in terms of obstructive airway disorder with chronic inflammation and mucous production, however reversibility is not a significant feature of it.

Question 15

What are the different COPD phenotypes, and what anatomical site defines them?

Answer 15

Emphysema: acinus, air space enlargement and wall destruction

Chronic bronchitis: bronchus, mucous gland hypertrophy and hyperplasia, hyper secretion

Question 16

What is bronchiectasis and what are its causes?

Answer 16

Permanent dilation of bronchi and bronchioles caused by destruction of the muscle and supporting elastic tissue, resulting from or associated with chronic necrotising infections

1. Bronchial obstruction (tumours, FB, impacted mucous)
2. Congenital abnormalities (CF, immunodeficiency, Kartagener Syndrome)
3. Necrotising pneumonia (particularly S. aureus)

Question 17

What are the 4 different categories of emphysema?

Answer 17

1. Centriacinar (Centrilobular)
2. Panacinar
3. Distal acinar (Paraseptal)
4. Irregular

Question 18

Define centriacinar emphysema?

Answer 18

Affecting central or proximal part of acinus formed bay respiratory bronchioles (i.e. sparing distal alveoli)

More common and severe in upper lobes, associated with smoking. Not seen in alpha-1 antitryspin deficiency

Question 19

Define panacinar emphysema?

Answer 19

Affects acini uniformly, causing enlargement from level of bronchioles to terminal alveoli

Affects lower zones

Common in A-1 antitrypsin deficiency

Question 20

Define distal acinar/paraseptal emphysema:

Answer 20

Primarily distal acini, with proximal segment sparing.

Large, multiple, contiguous enlarged airspaces with progressive enlargement –> “bullae”

Commonly adjacent to pleura, usually close to adjacent fibrosis, scarring, atelectasis, upper zones, most at risk of spontaneous pneumothorax

Question 21

Describe pathogenesis of emphysema?

Answer 21

Exposure to toxin –> inflammation (neutrophils, macrophages) –> release of elastase and cytokines –> epithelial injury and proteolysis of ECM –>insufficiency wound repair –> acini enlargement and destruction of lobule walls

Question 22

What are additional complications of COPD?

Answer 22

Pulmonary hypertension
Respiratory failure
Cor pulmonale

Question 23

What pressure would be equated with pulmonary HTN?

Answer 23

Pulmonary arterial pressure > 25mmHg at rest

Question 24

What mechanism is the most common by which pHTN develops?

Answer 24

Decreased in cross sectional area of pulmonary vascular bed or increase in pulmonary vascular blood flow

Question 25

What are the causes of pulmonary hypertension?

Answer 25

COPD/ILD: destruction of lung parenchyma and reduction of alveolar capillaries

Recurrent PEs: reduction in functional cross sectional area of pulmonary vascular bed

RIGHT heart failure: raised left atrial pressure –> higher venous pressure –> higher pulmonary arterial pressure as result

Congenital R to L shunts

Question 26

What is ARDS?

Answer 26

Clinical syndrome:
- Diffuse alveolar capillary and epithelial damage
- Characterised by rapid onset life-threatening respiratory failure refractory to oxygen therapy

Question 27

What is the histological finding in ARDS?

Answer 27

Diffuse alveolar damage (DAD)

Alveolar oedema, epithelial necrosis, accumulation of neutrophils, presence of hyaline membrane lining in alveolar ducts

Question 28

What are common and uncommon causes of ARDS?

Answer 28

Common:
- Pneumonia, aspiration
- Indirectly via sepsis, or trauma induced shock

Uncommon:
- PE, pulmonary contusion, fat emboli, drowning
- Indirectly via cardiopulmonary bypass, acute pancreatitis, drug overdose, uraemia

Question 29

What is the pathogenesis of ARDS?

Answer 29

Compromised integrity of respiratory membrane (alveolar/capillary) –> vascular permeability, alveolar flooding, loss of diffusion capacity, loss of surfactant due to damage to Type II pneumocytes

Damaged pneumocytes release IL-8, IL-1, TNF, chemotaxis for neutrophils –> proteases and damage the membrane further