Vascular-Origin Lung Disease lecture Flashcards
What is a pulmonary embolism and what determines its outcome?
Answer:
A pulmonary embolism (PE) is the obstruction of pulmonary arteries by a thrombus, usually originating from the deep leg veins.
The outcome depends on:
Size of the embolus: large (e.g. saddle embolus) can cause sudden death; small emboli may lead to pulmonary infarction
Underlying lung condition: e.g., prior emboli, infarcts, pulmonary hypertension, or cor pulmonale
Why does a pulmonary embolism not always cause infarction?
Answer:
The lung has a dual blood supply: the pulmonary arteries and bronchial arteries. This redundancy allows some areas to remain perfused even if a pulmonary artery is blocked. Infarction typically occurs only if:
The bronchial supply is insufficient
The patient has underlying lung disease or vascular compromise
What defines pulmonary hypertension and what are its causes?
Answer:
Pulmonary hypertension is defined as pulmonary arterial pressure >25% of systemic (aortic) pressure (normal is ~12.5%).
Causes:
Primary (idiopathic): possibly autoimmune or smooth muscle/endothelial dysfunction
Secondary:
Chronic lung disease (e.g., COPD, fibrosis)
Congenital or acquired heart disease (e.g., mitral stenosis)
Recurrent thromboembolism
What is cor pulmonale and how does it relate to pulmonary hypertension?
Answer:
Cor pulmonale is right-sided heart failure due to pulmonary hypertension.
Chronic high resistance in the pulmonary circulation forces the right ventricle to hypertrophy, eventually leading to failure.
What causes pulmonary oedema and how does it present?
Answer:
Pulmonary oedema is caused by fluid accumulation in alveoli due to:
Increased hydrostatic pressure (e.g., left-sided heart failure, mitral stenosis)
Decreased oncotic pressure (e.g., hypoalbuminaemia, nephrotic syndrome) Presents with:
Engorged vessels, basal fluid accumulation, microhaemorrhages, and pink frothy sputum
Haemosiderin-laden macrophages (“heart failure cells”)
Describe the pathogenesis of ARDS (Acute Respiratory Distress Syndrome).
Answer:
ARDS results from diffuse alveolar capillary damage leading to:
Loss of endothelial and epithelial barriers
Protein-rich exudate → hyaline membrane formation (fibrin + dead cells)
Type II pneumocyte proliferation Causes include:
Sepsis
Severe viral infection (e.g., COVID-19)
Inhaled toxins
Radiation
Near drowning
What is the Berlin Definition of ARDS?
Answer:
ARDS is an acute, diffuse inflammatory lung injury characterized by:
↑ Vascular permeability
↑ Lung weight
↓ Aerated lung tissue
Hypoxemia, bilateral radiographic opacities
↓ lung compliance, ↑ venous admixture
Explain the role of endothelial and epithelial injury in ARDS.
Answer:
Epithelial injury: viruses (like COVID-19), toxins → destroys type I pneumocytes, leads to leaky alveolar barrier
Endothelial injury: systemic infections (e.g., sepsis) → cytokine storm, vascular leak, fibrin deposition
Together, they cause alveolar flooding, inflammation, and fibrosis
What is the role of immune cells and cytokines in ARDS?
Answer:
Neutrophils release ROS, proteases, and inflammatory mediators (IL-8, TNF, C5a)
Monocytes and lymphocytes infiltrate tissue
Cytokines drive epithelial/endothelial damage, leading to hyaline membranes and impaired gas exchange
How does ARDS contribute to COVID-19 mortality?
Answer:
In COVID-19:
SARS-CoV-2 first infects epithelial cells, then endothelial cells
Triggers innate immune activation, cytokine storm, and vascular damage
Leads to pulmonary oedema, diffuse alveolar damage, and multi-organ failure
ARDS is a major mechanism of respiratory failure and death
What are extracellular vesicles (EVs) and how are they involved in ARDS?
Answer:
EVs are small membrane-bound particles released by cells, including:
Exosomes, microvesicles, apoptotic bodies In ARDS:
EVs from platelets, PMNs, and endothelial cells carry inflammatory mediators
Contribute to coagulopathy, inflammation, and organ dysfunction
Play a role in COVID-19-associated thrombopathy
Describe key pathological features seen in the lungs during ARDS.
Answer:
Collapsed or consolidated lung areas
Interstitial thickening and fibrosis
Hyaline membranes lining alveoli
Reduced lung compliance
V/Q mismatch, hypoxia, rare full resolution
What is “CALI” and how does it differ from classical ARDS?
Answer:
CALI (COVID-19-Associated Lung Injury) is a more severe, systemic version of ARDS caused by SARS-CoV-2. It involves:
Epithelial injury → endothelial dysfunction
Systemic cytokine storm
Severe vascular leak, thrombosis, and multi-organ involvement
Extensive EV release exacerbating inflammation
How can extracellular vesicles serve as therapeutic targets in ARDS?
Answer:
Since EVs mediate cell-cell communication and contribute to inflammation, thrombosis, and fibrosis, targeting their release, uptake, or cargo could:
Limit vascular injury
Reduce cytokine spread
Improve tissue repair
