The pulmonary microvessels serve as primary sites for fluid and solute exchange within the lung tissue. Starling forces govern fluid filtration from microvessels into the surrounding perimicrovascular interstitial space. The pulmonary lymphatics collect fluid and protein leaking into the interstitium and return the fluid and dissolved solute to the vascular system. Pathophysiologic events and mediators that substantially perturb the Starling forces culminate in pulmonary edema.


Adherens junction: An anchoring junction between two cells (made up of cadherin and associated proteins) that is linked to the actin cytoskeleton.

Edema: Swelling or excessive buildup of fluid in the tissues, or an increase in tissue mass due to fluid accumulation.

Fluid filtration: The passage of a liquid through a porous membrane resulting from a hydrostatic pressure difference.

Reflection coefficient: A measure of the relative permeability of a particular membrane to a particular solute calculated as the ratio of observed osmotic pressure to that calculated from van't Hoff's law.

Vascular permeability: The velocity of transport through the endothelial barrier through any or all of the following pathways: (1) between the cells, (2) through the cells, via pores (diaphragms or fused vesicles), and (3) transcellularly, via shuttling vesicles and specific receptors.


1. John et al. (2003). Am. J. Physiol. Lung Cell. Mol. Physiol. 284, L187-L196.

2. Lum and Malik (1994). Am. J. Physiol. 267, L223-L241.

3. Negrini et al. (1996). Am. J. Physiol. 270, H2000-H2007.

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5. Rutschman et al. (1993). J. Appl. Physiol. 75, 1574-1580.

7. Sandoval et al. (2001). J. Physiol. 533.2, 433-445.

8. Birukova et al. (2004). Microvasc. Res. 67, 64-77.

Further Reading

Dudek, S. M., and Garcia, J. G. N. (2001). Cytoskeletal regulation of pulmonary vascular permeability. J. Appl. Physiol. 91, 1487-1500. This article provides an outstanding overview of the endothelial cell signaling mechanisms and effector proteins that mediate thrombin-induced increase in endothelial permeability as well as mechanisms that stabilize or maintain endothelial barrier integrity.

Flick, M. R., and Matthay, M. A. (2000). Pulmonary edema and acute lung injury. In Textbook of Respiratory Medicine (J. F. Murray and J. A. Nadel, eds.), 3rd ed., pp. 1575-1629. Philadelphia: W.B. Saunders.

Malik, A. B., Vogel, S. M., Minshall, R. D., and Tiruppathi, C. (2000). Pulmonary circulation and regulation of fluid balance. In Textbook of Respiratory Medicine pp. 119-154. 3rd edition, (J. F. Murray and J. A. Nadel, eds.), Philadelphia: W.B. Saunders.

Minshall, R. D., Tiruppathi, C., Vogel, S. M., and Malik, A. B. (2002). Vesicle formation and trafficking and its role in regulation of endothelial barrier function. Histochem. Cell Biol. 117, 105-112. This review outlines the signaling mechanisms involved in caveolae-mediated endocy-tosis and transcytosis of albumin in endothelial cells. This transcellular transport mechanism is an important determinant of basal albumin permeability and nutrient/hormone delivery into the tissue when cell—cell junctions are intact.

Taylor, A. E. and Parker, J. C. (1985). Pulmonary interstitial spaces and lymphatics. In Handbook of Physiology. Section 3: The Respiratory System. Circulation and Nonrespiratory Function (A. P. Fishman and

A. B Fisher, eds.), Vol. 1, pp. 167-230. Bethesda, MD: American Physiological Society.

Tuma, P. L., and Hubbard, A. L. (2003). Transcytosis: Crossing cellular barriers. Physiol. Rev. 83, 871-932. Tiruppathi, C., Minshall, R. D., Paria, B. C., Vogel, S. M., and Malik, A. B. (2003) Role of Ca2+ signaling in the regulation of endothelial permeability. Vasc. Pharmacol. 39, 173-185. This review summarizes the mechanisms which regulate intracellular calcium homeostasis (release mechanisms and influx pathways) in endothelial cells and their role in thrombin-induced increase in endothelial permeability.

Capsule Biographies

Dr. Richard Minshall is an Assistant Professor of Pharmacology and Anesthesiology at The University of Illinois at Chicago. A Parker Francis Fellow in Pulmonary Research from 2001 to 2004, his NIH-funded research focuses on the physiological and pathological roles transcellular and paracellular permeability pathways of the endothelium.

Dr. Stephen Vogel is an Assistant Professor of Pharmacology at The University of Illinois at Chicago investigating the mechanisms of protein and fluid permeability regulation in the lung. Dr. Vogel is regarded as a significant contributor in the lung biology field for the development of ex vivo isolated mouse and rat lung models used to investigate the physiological importance of caveolae-mediated albumin transport processes in the epithelial and endothelial cell barriers.

Essentials of Human Physiology

Essentials of Human Physiology

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