Intrapulmonary vascular shunt pathways in alveolar capillary dysplasia with misalignment of pulmonary veins

Abstract

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a lethal neonatal lung disease characterised by severe pulmonary hypertension, abnormal vasculature and intractable hypoxaemia. Mechanisms linking abnormal lung vasculature with severe hypoxaemia in ACD/MPV are unknown. We investigated whether bronchopulmonary anastomoses form right-to-left shunt pathways in ACD/MVP. We studied 2 infants who died of ACD/MPV postmortem with direct injections of coloured ink into the pulmonary artery, bronchial artery and pulmonary veins. Extensive histological evaluations included serial sectioning, immunostaining and 3-dimensional reconstruction demonstrated striking intrapulmonary vascular pathways linking the systemic and pulmonary circulations that bypass the alveolar capillary bed. These data support the role of prominent right-to-left intrapulmonary vascular shunt pathways in the pathophysiology of ACD/MPV.

Keywords: Histology/Cytology; Paediatric interstitial lung disease; Rare lung diseases.

Figure 1

Upper panel: Main components of intrapulmonary vascular anastomotic pathways are shown. Three-dimensional image reconstruction (A) and histological sections (B) show direct connections between pulmonary arteries (PA) and bronchial arteries (BA) (white arrow) (BA-yellow, PA-red and blue, Bronchus (Br)-green). In an age-matched control lung, BV and pulmonary veins (PV) connections are present but appear very delicate, almost invisible (C, insert magnifies BV-PV connection). In alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), the bronchial vessels are enlarged, especially the BV (D) appearing as dilated, thin-walled channels within the bronchovascular bundle (‘misaligned pulmonary veins’). Lower panel: Schematic of intrapulmonary right-to-left shunt in ACD/MPV lung is shown. The majority of right heart blood is shunted through the arterial bronchopulmonary anastomoses (PA, BA, mv) that drains via venous bronchopulmonary anastomoses (microvessels (mv), BV, PV) leading to significantly decreased flow within the alveolar capillary bed.