Nodular pulmonary amyloidosis.

An elderly man had a 10-year history of multiple pulmonary nodules that he had refused to have investigated. He died of a ruptured abdominal aortic aneurysm. At autopsy the nodules were shown to consist of amyloid. There was no evidence of systemic amyloidosis.     

Hypoxic pulmonary vasoconstriction.

Humans encounter hypoxia throughout their lives. This occurs by destiny in utero, through disease, and by desire, in our quest for altitude. Hypoxic pulmonary vasoconstriction (HPV) is a widely conserved, homeostatic, vasomotor response of resistance pulmonary arteries to alveolar hypoxia. HPV mediates ventilation-perfusion matching and, by reducing shunt fraction, optimizes systemic Po(2). HPV is intrinsic to the lung, and, although modulated by the endothelium, the core mechanism is in the smooth muscle cell (SMC). The Redox Theory for the mechanism of HPV proposes the coordinated action of a redox sensor (the proximal mitochondrial electron transport chain) that generates a diffusible mediator [a reactive O(2) species (ROS)] that regulates an effector protein [voltage-gated potassium (K(v)) and calcium channels]. A similar mechanism for regulating O(2) uptake/distribution is partially recapitulated in simpler organisms and in the other specialized mammalian O(2)-sensitive tissues, including the carotid body and ductus arteriosus. Inhibition of O(2)-sensitive K(v) channels, particularly K(v)1.5 and K(v)2.1, depolarizes pulmonary artery SMCs, activating voltage-gated Ca(2+) channels and causing Ca(2+) influx and vasoconstriction. Downstream of this pathway, there is important regulation of the contractile apparatus' sensitivity to calcium by rho kinase. Controversy remains as to whether hypoxia decreases or increases ROS and which electron transport chain complex generates the ROS (I and/or III). Possible roles for cyclic adenosine diphosphate ribose and an unidentified endothelial constricting factor are also proposed by some groups. Modulation of HPV has therapeutic relevance to cor pulmonale, high-altitude pulmonary edema, and sleep apnea. HPV is clinically exploited in single-lung anesthesia, and its mechanisms intersect with those of pulmonary arterial hypertension.     

Methadone-induced pulmonary edema.

A patient with methadone-induced pulmonary edema had increased extravascular water in the lungs and a reduced total vascular albumin space. Diuresis resulted in hypotension. These observations suggest that the appropriate treatment of this condition should be ventilatory support and restoration of plasma oncotic pressure with albumin. Diuretic therapy should be used with caution.