Page 479 - Textbook of Pathology, 6th Edition

also termed as hyaline membrane disease (HMD). The two i) The basic defect in neonatal ARDS is a deficiency of 463
forms of ARDS have different clinical settings, response to pulmonary surfactant, normally synthesised by type II alveolar
treatment and consequences, etiology, pathogenesis but have cells. The production of surfactant is normally increased
similar morphology, and hence are discussed together below. shortly before birth but in prematurity and in neonatal
hypoxia from any of the foregoing causes, its synthesis is
CLINICAL FEATURES AND CONSEQUENCES. These are
as under: decreased. The main function of alveolar surfactant being
lowering of alveolar surface tension, its deficiency leads to
Neonatal ARDS occurring in newborn infants begins increased alveolar surface tension which in turn causes
with dyspnoea within a few hours after birth with atelectasis.
tachypnoea, hypoxia and cyanosis; in severe cases death may ii) Atelectasis of the lungs results in hypoventilation, pulmo-
occur within a few hours. nary hypoperfusion and ischaemic damage to capillary
Adult ARDS is known by various synonyms such as endothelium.
shock-lung syndrome, diffuse alveolar damage (DAD), acute iii) This results in ischaemic necrosis of the alveolocapillary
alveolar injury, traumatic wet lungs and post-traumatic wall, exudation of plasma proteins including fibrinogen into
respiratory insufficiency. The condition was first recognised the alveoli and eventually formation of hyaline membrane
in adults during World War II in survivors of non-thoracic on the alveolar surface containing largely fibrin.
injuries with shock. Adult ARDS also presents clinically by Adult ARDS. The mechanism of acute injury by etiologic
sudden and severe respiratory distress, tachypnoea, agents listed above depends upon the imbalance between pro-
tachycardia, cyanosis and severe hypoxaemia. inflammatory and anti-inflammatory cytokines:
ETIOLOGY. The two forms of ARDS have distinct etiology: i) Activated pulmonay macrophages release proinflammatory
Neonatal ARDS is primarily initiated by hypoxia, either cytokines such as IL8, IL1, and tumour necrosis factor (TNF),
shortly before birth or immediately afterward. It occurs in while macrophage inhibitory factor (MIF) helps to sustain
following clinical settings: inflammation in the alveoli. Number of neutrophils in the
1. Preterm infants alveoli is increased in acute injury. Neutrophils on activation
2. Infants born to diabetic mothers release products which cause active tissue injury e.g.
3. Delivery by caesarean section proteases, platelet activating factor, oxidants and CHAPTER 17
4. Infants born to mothers with previous premature infants leukotrienes.
5. Excessive sedation of the mother causing depression in ii) Besides the role of cytokines in acute injury, a few fibrogenic
respiration of the infant cytokines such as transforming growth factor-α (TGF-α) and
6. Birth asphyxia from various causes such as coils of platelet-derived growth factor (PDGF) play a role in repair
umbilical cord around the neck process by stimulation of proliferation of fibroblast and
7. Male preponderance (1.5 to 2 times) over female babies collagen.
due to early maturation of female lungs In either case, injury to the capillary endothelium leads
8. Finally, many cases of neonatal ARDS remain idio- to increased vascular permeability while injured
pathic. pneumocytes, especially type 1, undergo necrosis. The net
effect of injury to both capillary endothelium and alveolar
Adult ARDS may occur from the following causes: The Respiratory System
1. Shock due to sepsis, trauma, burns epithelium is interstitial and intra-alveolar oedema,
2. Diffuse pulmonary infections, chiefly viral pneumonia congestion, fibrin deposition and formation of hyaline
3. Pancreatitis membranes. As a result of coating of the alveoli with hyaline
4. Oxygen toxicity membranes, there is loss of surfactant causing collapse called
5. Inhalation of toxins and irritants e.g. smoke, war gases, ‘stiff lung’. There is an attempt at regeneration of alveolar
nitrogen dioxide, metal fumes etc. cells by proliferation of type II alveolar cells so as to increase
6. Narcotic overdose the secretion of surfactant.
7. Drugs e.g. salicylates, colchicine MORPHOLOGIC FEATURES. Grossly, the lungs are
8. Aspiration pneumonitis normal in size. They are characteristically stiff, congested,
9. Fat embolism heavy and airless so that they sink in water.
10. Radiation. Microscopically, the important features are as follows
PATHOGENESIS. In both neonatal and adult type ARDS, (Fig. 17.4):
there is damage to alveolocapillary wall triggered by etiologic 1. There is presence of collapsed alveoli (atelectasis) alter-
factors listed above, and the final pathologic consequence of nating with dilated alveoli.
formation of hyaline membrane is also similar. However, 2. Necrosis of alveolar epithelial cells and formation of
how it occurs is different in the neonates than in adults. The characteristic eosinophilic hyaline membranes lining the
sequence of events in the pathogenesis of both neonatal and respiratory bronchioles, alveolar ducts and the proximal
adult ARDS is schematically illustrated in Fig. 17.3 and is alveoli. The membrane is largely composed of fibrin
outlined below: admixed with cell debris derived from necrotic alveolar
cells.
Neonatal ARDS. Entry of air into alveoli is essential for 3. Interstitial and intra-alveolar oedema, congestion and
formation of hyaline membrane i.e. dead born infants do not develop intra-alveolar haemorrhages.
HMD.