Week 14 Pathology - Lungs I Flashcards
What is atelectasis?
Loss of lung volume due to inadequate expansion of air space
How does atelectasis cause hypoxia?
Results in shunting of inadequately oxygenated blood from pulmonary arteries into pulmonary veins, leading to ventilation/perfusion mismatch and hypoxia
What are the 3 types of atelectasis?
- Resorption
- Compression
- Contraction
What is resorption atelectasis?
Obstruction prevents air from reaching distal airways, caused by mucus plug or FB, typically affecting post op patients, asthma, bronchiectasis, tumour
What is compression atelectasis?
due to accumulation of fluid, blood, air within pleural cavity –> mechanical collapse
causes include pleural effusion, PTX, ascites
What is contraction atelectasis?
Local or generalised fibrotic changes in lung/pleura hamper expansion and increase elastic recoil in expiration (i.e. ILD)
Define asthma:
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
What T helper cell phenotype is largely responsible for asthma?
Th2 response - exaggerated greatly in atopic asthma patients.
What are the cytokines responsible, and their effects?
**Think letters of the alphabet
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)
What is the brief pathophysiology of asthma attack?
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
What is airway remodelling, and how does it relate to asthma?
Repeat episodes of inflammation cause remodelling, largely hypertrophy of bronchial smooth muscle and mucus glands, increased vascularity and deposition of sub endothelial collagen (fibrosis)
How can you classify asthma?
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
What are some histological findings of chronic asthma?
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
What is the major difference in definition of COPD?
Much the same in terms of obstructive airway disorder with chronic inflammation and mucous production, however reversibility is not a significant feature of it.
What are the different COPD phenotypes, and what anatomical site defines them?
Emphysema: acinus, air space enlargement and wall destruction
Chronic bronchitis: bronchus, mucous gland hypertrophy and hyperplasia, hyper secretion
What is bronchiectasis and what are its causes?
Permanent dilation of bronchi and bronchioles caused by destruction of the muscle and supporting elastic tissue, resulting from or associated with chronic necrotising infections
- Bronchial obstruction (tumours, FB, impacted mucous)
- Congenital abnormalities (CF, immunodeficiency, Kartagener Syndrome)
- Necrotising pneumonia (particularly S. aureus)
What are the 4 different categories of emphysema?
- Centriacinar (Centrilobular)
- Panacinar
- Distal acinar (Paraseptal)
- Irregular
Define centriacinar emphysema?
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
Define panacinar emphysema?
Affects acini uniformly, causing enlargement from level of bronchioles to terminal alveoli
Affects lower zones
Common in A-1 antitrypsin deficiency
Define distal acinar/paraseptal emphysema:
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
Describe pathogenesis of emphysema?
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
What are additional complications of COPD?
Pulmonary hypertension
Respiratory failure
Cor pulmonale
What pressure would be equated with pulmonary HTN?
Pulmonary arterial pressure > 25mmHg at rest
What mechanism is the most common by which pHTN develops?
Decreased in cross sectional area of pulmonary vascular bed or increase in pulmonary vascular blood flow
What are the causes of pulmonary hypertension?
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
What is ARDS?
Clinical syndrome:
- Diffuse alveolar capillary and epithelial damage
- Characterised by rapid onset life-threatening respiratory failure refractory to oxygen therapy
What is the histological finding in ARDS?
Diffuse alveolar damage (DAD)
Alveolar oedema, epithelial necrosis, accumulation of neutrophils, presence of hyaline membrane lining in alveolar ducts
What are common and uncommon causes of ARDS?
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
What is the pathogenesis of ARDS?
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
