: Dani S. Zander, Helmut H. Popper, Jaishree Jagirdar, und Abida K. Haque
: Dani S. Zander, Helmut Popper, Jaishree Jagirdar, Abida Haque, Roberto Barrios, Philip T. Cagle
: Molecular Pathology of Lung Diseases
: Springer-Verlag
: 9780387724300
: 1
: CHF 193.20
:
: Klinische Fächer
: English
: 682
: Wasserzeichen/DRM
: PC/MAC/eReader/Tablet
: PDF

This major work, complete with 150 illustrations, many of them in color, bridges the gap between clinical pulmonary pathology and basic molecular science. Through a highly visual approach that features an abundance of tables and diagrams, the book offers a practical disease-based overview. The first two sections of the volume provide the reader with general concepts, terminology and procedures in molecular pathology. The remainder of the volume is subdivided into neoplastic and non-neoplastic lung diseases with detailed chapters covering the current molecular pathology of specific diseases. The book will be essential reading for pathologists, pulmonologists, thoracic surgeons and other health care providers interested in lung disease.
"Section 5 Molecular Pathology of Pulmonary Infections (p. 369-370)

36 Basis of Susceptibility to Lung Infection

Frank C. Schmalstieg and Armond S. Goldman

Introduction

The myriad microbial pathogens encountered by the lung presents a daunting challenge to the human immune system. Nowhere else in the body is such a vast surface area (approximately 100 m2)1 directly exposed to airborne pathogens at about 20 times per minute. Not only is the area and exposure extreme, but the underlying blood circulation is only two cell layers, of about 0.5μm each, removed from the alveolar surface. Furthermore, gravity and manifold branching of bronchioles and bronchi interfere with the expulsion of these organisms and tissue debris that occurs during lung infection. It is not surprising, then, that pneumonias are among the most common infectious diseases in the United States.

Understanding the susceptibility to lung infection requires a comprehension of (1) the anatomy and function of the lung, (2) environmental exposures, (3) systemic and mucosal immune functions, (4) virulence of pathogens, and (5) genetic variabilities of the host defenses. Numerous“experiments of nature” and identi- ? cation of the molecular mechanisms of pathogen entry into lung cells especially have provided unique insights into understanding immune aspects of host susceptibility. More recently, rapid, high volume methods of analyzing potential genetic determinants for host susceptibility to speci? c pathogens have shown considerable promise. These considerations and their results are explored in some detail in this chapter.

Lung Anatomy and Function

Unique Aspects of the Lung Microcirculation

Three distinct circulations supply the lung and airways with blood. They are the tracheal, bronchial, and pulmonary circulations. The tracheal arteries branch from the superior and inferior thyroid arteries and drain to the inferior thyroid venous plexus. More importantly, the bronchial arterial supply is from the thoracic aorta, and the venous drainage from this artery is largely (∼70%) anastomosed to the pulmonary circulation in a precapillary location3 in the sheep. This also likely occurs in humans.

These anastomoses are signi? cant because neutrophils may be in? uenced by mediators from airway epithelium and then interact directly with the pulmonary capillaries, thus providing a connection with in? ammation in the airway and in the alveolar capillaries. In this regard, the capillary diameter in the bronchial microcirculation is about 8.5μm but only approximately 5.5μm in the pulmonary capillaries.4 Neutrophils have to deform during passage through the pulmonary capillaries (Figure 36.1) because of their relatively large diameter (10– 15μm).

In contrast, erythrocytes pass through those capillaries more readily because of their smaller diameters. Delay in the passage of neutrophils results in a relative increase in neutrophil concentration in the pulmonary capillaries.5 This may be an adaptive modi? cation for better control of any organisms breaching the extensive and exposed surfaces of the alveoli.

The slowing and momentary stopping of neutrophils in the pulmonary capillaries under certain stimuli may allow selectin- and integrin-independent migration of these cells from the capillaries.6,7 The bronchial circulation is also unique in that airway injury can stimulate a ? vefold increase in bronchial blood ? ow in sheep.

Although the increased blood ? ow during injury amounts to less than 3% of the cardiac output, neutrophils activated in the bronchial microcirculation may be directly delivered to the pulmonary capillaries to produce damage. In fact, bronchial artery ligation decreases lung edema in a sheep model of smoke and burn injury.9 The anatomy of the lung then potentially allows damage in the airway to produce in? ammatory changes in the lung that may enhance lung protection or lead to further damage under some circumstances."