Human hemorrhagic pulmonary leptospirosis: pathological findings and pathophysiological correlations

• Published in: PloS one Vol. 8; no. 8; p. e71743
• Main Authors: De Brito, Thales, Aiello, Vera Demarchi, da Silva, Luis Fernando Ferraz, Gonçalves da Silva, Ana Maria, Ferreira da Silva, Wellington Luiz, Castelli, Jussara Bianchi, Seguro, Antonio Carlos
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.08.2013; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Alveolar Epithelial Cells - metabolism; Alveolar Epithelial Cells - pathology; Alveoli; Antibodies; Aquaporin 1; Aquaporin 5; Aquaporins; Blood vessels; Blood Vessels - metabolism; Blood Vessels - pathology; Case-Control Studies; CD34 antigen; Connexin 43; Connexin 43 - metabolism; Cytoplasm; Damage; Disease; Edema; Endothelial cells; Epithelial Sodium Channels - metabolism; Eutrophication; Female; Heart; Hemorrhage; Humans; Immunoglobulins; Immunohistochemistry; Inflammation; Laboratories; Leptospirosis; Lung - metabolism; Lung - pathology; Lung diseases; Lung Diseases - pathology; Lung Diseases - physiopathology; Lungs; Male; Medical research; Medical schools; Medicine; Microcirculation; Microscopy, Confocal; Middle Aged; Pathogenesis; Pathology; Patients; Pneumocytes; Restoration; Rodents; Sepsis; Septicemia; Sodium; Studies; Transport; Water transport; Weil Disease - pathology; Weil Disease - physiopathology; Young Adult; Zoonoses; Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0071743

Leptospirosis is a re-emerging zoonosis with protean clinical manifestations. Recently, the importance of pulmonary hemorrhage as a lethal complication of this disease has been recognized. In the present study, five human necropsies of leptospirosis (Weil's syndrome) with extensive pulmonary manifestations were analysed, and the antibodies expressed in blood vessels and cells involved in ion and water transport were used, seeking to better understand the pathophysiology of the lung injury associated with this disease. Prominent vascular damage was present in the lung microcirculation, with decreased CD34 and preserved aquaporin 1 expression. At the periphery and even inside the extensive areas of edema and intraalveolar hemorrhage, enlarged, apparently hypertrophic type I pneumocytes (PI) were detected and interpreted as a non-specific attempt of clearence of the intraalveolar fluid, in which ionic transport, particularly of sodium, plays a predominant role, as suggested by the apparently increased ENaC and aquaporin 5 expression. Connexin 43 was present in most pneumocytes, and in the cytoplasm of the more preserved endothelial cells. The number of type II pneumocytes (PII) was slightly decreased when compared to normal lungs and those of patients with septicemia from other causes, a fact that may contribute to the progressively low PI count, resulting in deficient restoration after damage to the alveolar epithelial integrity and, consequently, a poor outcome of the pulmonary edema and hemorrhage. Pathogenesis of lung injury in human leptospirosis was discussed, and the possibility of primary non-inflammatory vascular damage was considered, so far of undefinite etiopathogenesis, as the initial pathological manifestation of the disease.