Mechanisms of pleural liquid accumulation in disease
- V Courtney Broaddus, MD
V Courtney Broaddus, MD
- Section Editor — Pleural Disease
- Professor of Medicine
- University of California San Francisco
In the normal pleural space, there is a steady state in which there is a roughly equal rate of the formation (entry) and absorption (exit) of liquid (figure 1). (See "Mechanisms of pleural liquid turnover in the normal state".) This balance must be disturbed in order to produce a pleural effusion. Thus, there must be an increase in entry rate and/or a reduction in exit rate. It is likely that both mechanisms contribute to effusion formation for the following reasons:
●An isolated increase in entry rate, unless large and sustained, is unlikely to cause a clinically significant effusion because the absorbing pleural lymphatics have a large reserve capacity to deal with excess pleural liquid. If, for example, artificial hydrothoraces are instilled into the pleural space of awake sheep, the exit rate can increase to 0.28 mL/kg per hour, which is 28 times the baseline rate .
●An isolated decrease in exit rate is also unlikely to cause a large effusion because the normal entry rate is low. Even if the exit of liquid ceased entirely, accumulation of liquid would take many days to become evident. As an example, the normal entry rate of 0.01 mL/kg per hour is equivalent to a total of 12 mL/day in a 50 kg woman; at this rate of entry without any exit of liquid, it would take more than one month days for 500 mL to accumulate in the pleural space. Of note, the effusion would presumably be a transudate, since the normal liquid entering the pleural space is low in protein.
INCREASED FLUID ENTRY
Excess liquid filters out of systemic microvessels based on a balance of hydrostatic and osmotic forces across a semipermeable membrane [2,3]. These forces are well described in the Starling equation, in which the hydrostatic forces that force water out of the vessel are balanced by osmotic forces that reabsorb water back into the vessel [4,5].
Flow = k x [(Pmv - Ppmv) - s (πmv - πpmv)]
Subscribers log in hereLiterature review current through: Sep 2017. | This topic last updated: Apr 15, 2016.References
- Broaddus VC, Wiener-Kronish JP, Berthiaume Y, Staub NC. Removal of pleural liquid and protein by lymphatics in awake sheep. J Appl Physiol (1985) 1988; 64:384.
- Staub NC, Wiener-Kronish JP, Albertine KH. Transport through the pleura: physiology of normal liquid and solute exchange in the pleural space, Marcel Dekker, New York 1985.
- Lai-Fook SJ. Pleural mechanics and fluid exchange. Physiol Rev 2004; 84:385.
- Starling EH. On the Absorption of Fluids from the Connective Tissue Spaces. J Physiol 1896; 19:312.
- Staub NC. Pulmonary edema. Physiol Rev 1974; 54:678.
- Erdmann AJ 3rd, Vaughan TR Jr, Brigham KL, et al. Effect of increased vascular pressure on lung fluid balance in unanesthetized sheep. Circ Res 1975; 37:271.
- Broaddus VC, Wiener-Kronish JP, Staub NC. Clearance of lung edema into the pleural space of volume-loaded anesthetized sheep. J Appl Physiol (1985) 1990; 68:2623.
- Staub NC, Nagano H, Pearce ML. Pulmonary edema in dogs, especially the sequence of fluid accumulation in lungs. J Appl Physiol 1967; 22:227.
- Gee MH, Havill AM. The relationship between pulmonary perivascular cuff fluid and lung lymph in dogs with edema. Microvasc Res 1980; 19:209.
- Mackersie RC, Christensen J, Lewis FR. The role of pulmonary lymphatics in the clearance of hydrostatic pulmonary edema. J Surg Res 1987; 43:495.
- Joseph J, Strange C, Sahn SA. Pleural effusions in hospitalized patients with AIDS. Ann Intern Med 1993; 118:856.
- Prais D, Kuzmenko E, Amir J, Harel L. Association of hypoalbuminemia with the presence and size of pleural effusion in children with pneumonia. Pediatrics 2008; 121:e533.
- Quick CM, Venugopal AM, Dongaonkar RM, et al. First-order approximation for the pressure-flow relationship of spontaneously contracting lymphangions. Am J Physiol Heart Circ Physiol 2008; 294:H2144.
- Hosking B, Makinen T. Lymphatic vasculature: a molecular perspective. Bioessays 2007; 29:1192.
- STEWART PB. The rate of formation and lymphatic removal of fluid in pleural effusions. J Clin Invest 1963; 42:258.
- Leckie WJ, Tothill P. Albumin turnover in pleural effusions. Clin Sci 1965; 29:339.
- Kraft A, Weindel K, Ochs A, et al. Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease. Cancer 1999; 85:178.
- Bradshaw M, Mansfield A, Peikert T. The role of vascular endothelial growth factor in the pathogenesis, diagnosis and treatment of malignant pleural effusion. Curr Oncol Rep 2013; 15:207.
- Giannou AD, Marazioti A, Spella M, et al. Mast cells mediate malignant pleural effusion formation. J Clin Invest 2015; 125:2317.
- Sahn SA. Malignant pleural effusions. Clin Chest Med 1985; 6:113.
- Apicella MA, Allen JC. A physiologic differentiation between delayed and immediate hypersensitivity. J Clin Invest 1969; 48:250.
- Porcel JM, Madroñero AB, Pardina M, et al. Analysis of pleural effusions in acute pulmonary embolism: radiological and pleural fluid data from 230 patients. Respirology 2007; 12:234.
- Rice TW. Pleural effusions in superior vena cava syndrome: prevalence, characteristics, and proposed pathophysiology. Curr Opin Pulm Med 2007; 13:324.
- Good JT Jr, Moore JB, Fowler AA, Sahn SA. Superior vena cava syndrome as a cause of pleural effusion. Am Rev Respir Dis 1982; 125:246.
- Mellins RB, Levine OR, Fishman AP. Effect of systemic and pulmonary venous hypertension on pleural and pericardial fluid accumulation. J Appl Physiol 1970; 29:564.
- Wiener-Kronish JP, Goldstein R, Matthay RA, et al. Lack of association of pleural effusion with chronic pulmonary arterial and right atrial hypertension. Chest 1987; 92:967.
- Wright RS, Quinones-Baldrich WJ, Anders AJ, Danovitch GM. Pleural effusion associated with ipsilateral breast and arm edema as a complication of subclavian vein catheterization and arteriovenous fistula formation for hemodialysis. Chest 1994; 106:950.
- Muthuswamy P, Alausa M, Reilly B. Clinical problem-solving. The effusion that would not go away. N Engl J Med 2001; 345:756.
- Wiener-Kronish JP, Broaddus VC. Interrelationship of pleural and pulmonary interstitial liquid. Annu Rev Physiol 1993; 55:209.
- RICHTER CP. The physiology and cytology of pulmonary edema and pleural effusion produced in rats by alpha-naphthyl thiourea (ANTU). J Thorac Surg 1952; 23:66.
- Miller KS, Harley RA, Sahn SA. Pleural effusions associated with ethchlorvynol lung injury result from visceral pleural leak. Am Rev Respir Dis 1989; 140:764.
- Wiener-Kronish JP, Broaddus VC, Albertine KH, et al. Relationship of pleural effusions to increased permeability pulmonary edema in anesthetized sheep. J Clin Invest 1988; 82:1422.
- Bernaudin JF, Theven D, Pinchon MC, et al. Protein transfer in hyperoxic induced pleural effusion in the rat. Exp Lung Res 1986; 10:23.
- Aberle DR, Wiener-Kronish JP, Webb WR, Matthay MA. Hydrostatic versus increased permeability pulmonary edema: diagnosis based on radiographic criteria in critically ill patients. Radiology 1988; 168:73.
- Wiener-Kronish JP, Matthay MA, Callen PW, et al. Relationship of pleural effusions to pulmonary hemodynamics in patients with congestive heart failure. Am Rev Respir Dis 1985; 132:1253.
- PILLAY VK. TOTAL PROTEINS IN SEROUS FLUIDS IN CARDIAC FAILURE. S Afr Med J 1965; 39:142.
- Chakko SC, Caldwell SH, Sforza PP. Treatment of congestive heart failure. Its effect on pleural fluid chemistry. Chest 1989; 95:798.
- Romero-Candeira S, Fernández C, Martín C, et al. Influence of diuretics on the concentration of proteins and other components of pleural transudates in patients with heart failure. Am J Med 2001; 110:681.
- Shinto RA, Light RW. Effects of diuresis on the characteristics of pleural fluid in patients with congestive heart failure. Am J Med 1990; 88:230.
- Broaddus VC. Diuresis and transudative effusions--changing the rules of the game. Am J Med 2001; 110:732.
- Shinohara H, Kominami R, Taniguchi Y, Yasutaka S. The distribution and morphology of lymphatic vessels on the peritoneal surface of the adult human diaphragm, as revealed by an ink-absorption method. Okajimas Folia Anat Jpn 2003; 79:175.
- Grimaldi A, Moriondo A, Sciacca L, et al. Functional arrangement of rat diaphragmatic initial lymphatic network. Am J Physiol Heart Circ Physiol 2006; 291:H876.
- Lieberman FL, Hidemura R, Peters RL, Reynolds TB. Pathogenesis and treatment of hydrothorax complicating cirrhosis with ascites. Ann Intern Med 1966; 64:341.
- Huang PM, Chang YL, Yang CY, Lee YC. The morphology of diaphragmatic defects in hepatic hydrothorax: thoracoscopic finding. J Thorac Cardiovasc Surg 2005; 130:141.
- INCREASED FLUID ENTRY
- Increase in permeability
- Increase in microvascular pressure
- Decrease in pleural pressure
- Decrease in plasma osmotic pressure
- DECREASED FLUID EXIT
- Intrinsic factors
- Extrinsic factors
- EFFUSION FORMATION AND DISEASE STATES
- EFFUSION FORMATION BY SITE
- Pleural microvessel hydrostatic pressure elevation
- Extrapleural or extrapulmonary
- SUMMARY AND RECOMMENDATIONS