Human Hemorrhagic Pulmonary Leptospirosis: Pathological Findings and Pathophysiological Correlations

Abstract

BackgroundLeptospirosis 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.Principal FindingsProminent 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.ConclusionsPathogenesis 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.

The Expression of Water and Ion Channels in Diffuse Alveolar Damage Is Not Dependent on DAD Etiology

“…However, studies with double-knockout mice for AQP1 and 5 revealed that the absence of these channels did not alter alveolar fluid clearance [5, 24], suggesting that aquaporins add little fluid clearance management if active salt transport is intact. Nevertheless, subsequent studies showed that the expression of lung AQPs are altered after ALI models [10–12, 25, 26]. Although marginally significant, our results showed that the AQP1 level was lower in the DAD group as reported in previous animal models.…”

“…We also found the increased expression of AQP5 in the DAD groups. The role of AQP5 in edema reabsorption in ALI models is controversial [10–12, 25, 26]. The AQP5 response to lung injury may fluctuate over time and is dependent on the intensity and type of injury [11, 12, 26].…”

Endothelial Glycocalyx Damage is Associated with Leptospirosis Acute Kidney Injury

“…11,12 Also, experimental and autopsy studies have shown endothelial necrosis and capillary thrombosis in lung tissue. 13,14 Another important component of the endothelium is the glycocalyx, a 1-μm carbohydrate-rich structure located at the top of the endothelium. It has antiadhesive and anticoagulant properties that protect the endothelium and maintain the vascular barrier function.…”

Specific CD4+T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis

“…It may lead to a severe multiorgan failure (Morbus Weil, or Weil's disease) (7). In recent years, life-threatening and fatal cases have been due most often to pulmonary hemorrhages caused by vasculitis of small vessels (1,6,(8)(9)(10).…”