Resp path: Pulmonary HPT & Diffuse alveolar damage

Question 1

What is pulmonary HPT?

Answer 1

when mean pulmonary artery pressure pressure is >/= 25mmHg at rest

Question 2

What is pulmonary arterial hypertension?

Answer 2

Pulmonary arterial hypertension Involvement of small pulmonary muscular arteries
e.g. in autoimmune diseases like systemic sclerosis. Can be “idiopathic”with a strong genetic predisposition

Question 3

How does congenital or acquired heart disease cause pulmonary HPT?

Answer 3

e.g.
mitral stenosis causing increase in left atrial pressure and pulmonary venous pressure that is transmitted to the pulmonary arterial vasculature

Question 4

How does lung disease/hypoxia cause pulmonary HPT?

Answer 4

interstitial lung
diseases that obliterate alveolar capillaries, causing increased pulmonary resistance to blood flow

Question 5

How does chronic thromboembolism cause P-HPT?

Answer 5

Recurrent pulmonary emboli reduces functional cross-sectional area of the pulmonary vasculature

Question 6

What pathological changes can be seen in arterioles and pulmonary arteries as a result of P-HPT? (3)

Answer 6

1. Medial hypertrophy
2. Thickening and replication of elastic lamina
3. Plexiform pulmonary arteriopathy in which intraluminal tuft of capillary formation occurs in dilated thin walled arteriolar branches

Question 7

What pathological changes can be seen in medium-sized pulmonary arteries as a result of P-HPT? (4)

Answer 7

Medial hypertrophy (not as marked in 2ndary P-HPT)
Concentric thickening of intima
Adventitial fibrosis
Thickening and replication of elastic lamina

Question 8

How do obstructive and restrictive lung diseases cause P-HPT?

Answer 8

Restrictive and obstructive lung diseases can affect the pulmonary arterial circulation. A reduction of normal lung parenchyma diminishes the pulmonary vascular bed, leading to pulmonary hypertension.

Question 9

What pathological changes can be seen in large pulmonary arteries as a result of P-HPT? (4)

Answer 9

atheromatous deposits

Question 10

What is Diffuse alveolar damage?

Answer 10

It is a form of acute restrictive lung disease resulting from capillary wall endothelial injury

Question 11

What is acute lung injury?

Answer 11

abrupt onset of hypoxemia and bilateral pulmonary oedema, in the absence of cardiac failure (i.e. non-cardiogenic)

Question 12

What is acute respiratory distress syndrome?

Answer 12

manifestation of severe ALI (clinical syndrome of progressive respiratory insufficiency)

Question 13

what are the causes of Diffuse Alveolar Damage? (8)

Answer 13

Causes: Both pulmonary and systemic disorders:
Diffuse pulmonary infections,
Gastric aspiration
Mechanical trauma including head injuries.
Physical trauma / injury e.g. Near-drowning, inhaled irritants e.g. Smoke,
Chemical Injury e.g. Barbiturate overdose,
Hematologic conditions e.g. Transfusion-associated lung injury (TRALI),
Miscellaneous conditions e.g Pancreatitis, uraemia.
If idiopathic = Acute interstitial pneumonia

Question 14

What does diffuse alveolar damage look like grossly?

Answer 14

This lung is virtually airless, diffusely firm, and rubbery with a glistening appearance on cut section.
Heavy firm red boggy lungs

Question 15

What decreases the lung CO diffusing capacity?

Answer 15

DAD causes severe hypoxemia. The lung diffusing capacity for carbon monoxide (Dlco) is reduced.
Diseases that affect the alveolar walls (DAD or emphysema) or the pulmonary capillary bed (thromboembolism or vasculitis) decrease the Dlco

Question 16

how does the process of diffuse alveolar damage occur?

Answer 16

Injury of pneumocytes and pulmonary endothelium initiates a cycle of increasing inflammation and pulmonary damage that impairs alveolar gas exchange. The hypoxemia is exacerbated by ventilation-perfusion mismatch, as the lesions are not evenly distributed.

Endothelial activation: Early event. Can occur primarily as a response to circulating inflammatory mediators in severe tissue injury or sepsis, or secondarily to pneumocyte injury that is sensed by resident alveolar macrophages which then secrete mediators e.g. TNF that act on the endothelium

Adhesion of neutrophils to activated endothelium and extravasation into interstitium and alveoli: Neutrophils then degranulate and release inflammatory mediators and neutrophil extracellular traps, setting up the vicious cycle of inflammation and lung damage

Accumulation of intra-alveolar fluid and formation of hyaline membranes: Occurs as the endothelial activation and injury causes leaky pulmonary capillaries. Surfactant abnormalities also occur due to damaged Type II alveolar pneumocytes. Hyaline membranes then form as a result of organization of the protein-rich oedema fluid and dead alveolar epithelial cells

Resolution of injury: If the inflammatory stimulus is removed, macrophages remove intra-alveolar debris and secrete fibrogenic cytokines e.g. TGF-βand PDGF, stimulating fibroblast growth and collagen deposition, resulting in fibrosis of alveolar walls. Residual type II pneumocytes proliferate to replace type I pneumocytes, and uninjured capillary endothelium proliferates to restore the endothelium

Question 17

How does DAD look microscopically?

Answer 17

Congestion, interstitial and intra-alveolar oedema,
inflammation, fibrin deposition and hyaline membranes lining alveolar walls (fibrin-rich)
Oedema fluid mixed with degenerating necrotic epithelial cells).
Proliferating or organizing stage –type II pneumocyte hyperplasia and granulation tissue. This can eventually resolve.
Late fibrotic stage – if granulation tissue doesn’t resolve, fibrosis of alveolar septa occurs and lung compliance decreases further.

Question 18

Clinical findings of DAD

Answer 18

Severe dyspnoea and tachypnoea, followed by respiratory failure, hypoxemia and cyanosis.
Loss of functional surfactant results in lungs becoming stiff, requiring intubation and high ventilatory pressures.

Question 19

Radiological findings in DAD

Answer 19

Diffuse bilateral infiltrates

Question 20

What is the clinical course of DAD?

Answer 20

Moderately high mortality rate due to sepsis, multiorgan failure or severe lung injury.
Most survivors recover pulmonary function but a minority develop chronic lung disease due to
fibrosis.