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Pathophysiology and etiology of edema in children

Rudolph P Valentini, MD
Section Editor
Tej K Mattoo, MD, DCH, FRCP
Deputy Editor
Melanie S Kim, MD


Edema is a clinical condition characterized by an increase in interstitial fluid volume and tissue swelling that can either be localized or generalized. Severe generalized edema is known as anasarca. More localized interstitial fluid collections include ascites and pleural effusions.

The diagnostic approach to edema is based upon a thoughtful approach to the pathogenesis of its formation. Once a diagnosis is established, specific treatment of the underlying disorder can be given. If specific therapy is not available, general treatment, such as optimization of fluid management, can be provided.

The pediatric disease processes associated with edema and the pathogenesis of edema will be described in this topic review. More detailed discussions of evaluation and management of edema in children as well as the pathophysiology of edema are presented separately. (See "Evaluation and management of edema in children".)


Normal physiology — Edema does not occur in normal subjects because of the tight balance of hemodynamic forces along the capillary wall and the intact function of the lymphatic system. While capillary hydrostatic pressure favors transcapillary fluid movement into the interstitium, the colloid oncotic pressure across the capillary favors the retention of fluid within the vessel (figure 1). Under normal circumstances, these competing forces result in a small net movement of fluid into the interstitium. The lymphatic vessels return this interstitial fluid to the venous system thereby preventing edema formation.

Pathophysiology of edema — The following physiologic processes result in edema formation:

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Literature review current through: Nov 2017. | This topic last updated: Apr 20, 2016.
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  1. Lamb FS. Heart failure. In: Saunders Manual of Pediatric Practice, Finberg L (Ed), WB Saunders, Philadelphia 1998. p.600.
  2. Gewitz MH, Woolf PK. Cardiac emergencies. In: Textbook of Pediatric Emergency Medicine, 5th ed, Fleisher GR, Ludwig S, Henretig FM (Eds), Lippincott Williams & Wilkins, Philadelphia 2006. p.717.
  3. Brouhard BH, et al. Acute postinfectious glomerulonephritis. In: Pediatric Kidney Disease, Edelmann CM (Ed), Little, Brown and Company, Boston 1992. p.1199.
  4. Blowey DL. Acute glomerulonephritis. In: Saunders Manual of Pediatric Practice, Finberg L (Ed), WB Saunders, Philadelphia 1998. p.688.
  5. Issa PY, Brihi ER, Janin Y, Slim MS. Superior vena cava syndrome in childhood: report of ten cases and review of the literature. Pediatrics 1983; 71:337.
  6. Hagani A. Thrombophilia. In: Saunders Manual of Pediatric Practice, Finberg L (Ed), WB Saunders Company, Philadelphia 1998. p.431.
  7. Chase HP, Kumar V, Caldwell RT, O'Brien D. Kwashiorkor in the United States. Pediatrics 1980; 66:972.
  8. Martin PY, Ginès P, Schrier RW. Nitric oxide as a mediator of hemodynamic abnormalities and sodium and water retention in cirrhosis. N Engl J Med 1998; 339:533.
  9. Brasitus TA. Protein-losing gastroenteropathy. In: Gastrointestinal Disease: Pathophysiology, Diagnosis, Management, Sleisenger JS (Ed), WB Saunders, Philadelphia 1993. p.1027.
  10. Thomas DW, et al. Protein-losing enteropathy. In: Principles and Practice of Pediatrics, Oski CD, Feigin RD, Warshaw JB (Eds), J.B. Lippincott Company, Philadelphia 1990. p.1722.
  11. Weir MR, Rosenberger C, Fink JC. Pilot study to evaluate a water displacement technique to compare effects of diuretics and ACE inhibitors to alleviate lower extremity edema due to dihydropyridine calcium antagonists. Am J Hypertens 2001; 14:963.
  12. Zingale LC, Beltrami L, Zanichelli A, et al. Angioedema without urticaria: a large clinical survey. CMAJ 2006; 175:1065.
  13. Davis RS, Vandewalker ML, Hutcheson PS, Slavin RG. Facial angioedema in children due to ladybug (Harmonia axyridis) contact: 2 case reports. Ann Allergy Asthma Immunol 2006; 97:440.
  14. Svenningsen P, Bistrup C, Friis UG, et al. Plasmin in nephrotic urine activates the epithelial sodium channel. J Am Soc Nephrol 2009; 20:299.
  15. Rondon-Berrios H. [New insights into the pathophysiology of oedema in nephrotic syndrome]. Nefrologia 2011; 31:148.
  16. Valentini RP, Smoyer WE. Nephrotic Syndrome. In: Clinical Pediatric Nephrology, 2nd ed, Kher KK, Schnaper HW, Makker SP (Eds), Informa Healthcare, London 2007. p.155.
  17. McAdams AJ, Valentini RP, Welch TR. The nonspecificity of focal segmental glomerulosclerosis. The defining characteristics of primary focal glomerulosclerosis, mesangial proliferation, and minimal change. Medicine (Baltimore) 1997; 76:42.
  18. Menon S, Valentini RP. Membranous nephropathy in children: clinical presentation and therapeutic approach. Pediatr Nephrol 2010; 25:1419.
  19. Olson JL, Schwartz MM. The Nephrotic Syndrome: Minimal change disease. Focal segmental glomerulosclerosis, and miscellaneous causes. In: Heptinstall's pathology of the kidney, Jennette JL, Schwartz MM, Silva FG (Eds), Lippincott-Raven, Philadelphia 1998. p.187.
  20. Rockson SG. Lymphedema. Am J Med 2001; 110:288.
  21. Lawenda BD, Mondry TE, Johnstone PA. Lymphedema: a primer on the identification and management of a chronic condition in oncologic treatment. CA Cancer J Clin 2009; 59:8.
  22. Szuba A, Rockson SG. Lymphedema: classification, diagnosis and therapy. Vasc Med 1998; 3:145.
  23. Lewis JM, Wald ER. Lymphedema praecox. J Pediatr 1984; 104:641.
  24. Harel L, Amir J, Nussinovitch M, et al. Lymphedema praecox seen as isolated unilateral arm involvement: case report and review of the literature. J Pediatr 1997; 130:492.
  25. Wheeler ES, Chan V, Wassman R, et al. Familial lymphedema praecox: Meige's disease. Plast Reconstr Surg 1981; 67:362.
  26. Connell F, Brice G, Mortimer P. Phenotypic characterization of primary lymphedema. Ann N Y Acad Sci 2008; 1131:140.
  27. Finegold DN, Kimak MA, Lawrence EC, et al. Truncating mutations in FOXC2 cause multiple lymphedema syndromes. Hum Mol Genet 2001; 10:1185.
  28. Fang J, Dagenais SL, Erickson RP, et al. Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. Am J Hum Genet 2000; 67:1382.
  29. Petrova TV, Karpanen T, Norrmén C, et al. Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis. Nat Med 2004; 10:974.
  30. Mellor RH, Brice G, Stanton AW, et al. Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb. Circulation 2007; 115:1912.
  31. Warren AG, Brorson H, Borud LJ, Slavin SA. Lymphedema: a comprehensive review. Ann Plast Surg 2007; 59:464.
  32. Evans AL, Brice G, Sotirova V, et al. Mapping of primary congenital lymphedema to the 5q35.3 region. Am J Hum Genet 1999; 64:547.
  33. Ferrell RE, Levinson KL, Esman JH, et al. Hereditary lymphedema: evidence for linkage and genetic heterogeneity. Hum Mol Genet 1998; 7:2073.
  34. Karkkainen MJ, Ferrell RE, Lawrence EC, et al. Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. Nat Genet 2000; 25:153.
  35. Mäkinen T, Jussila L, Veikkola T, et al. Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nat Med 2001; 7:199.
  36. Bull LN, Roche E, Song EJ, et al. Mapping of the locus for cholestasis-lymphedema syndrome (Aagenaes syndrome) to a 6.6-cM interval on chromosome 15q. Am J Hum Genet 2000; 67:994.
  37. Witt C, Ottesen EA. Lymphatic filariasis: an infection of childhood. Trop Med Int Health 2001; 6:582.
  38. Athreya BH, Ostrov BE, Eichenfield AH, Goldsmith DP. Lymphedema associated with juvenile rheumatoid arthritis. J Rheumatol 1989; 16:1338.
  39. Murphy MJ, Kogan B, Carlson JA. Granulomatous lymphangitis of the scrotum and penis. Report of a case and review of the literature of genital swelling with sarcoidal granulomatous inflammation. J Cutan Pathol 2001; 28:419.