title: Mechanisms and implications of hypoalbuminemia in head-injured patients.
abstract: Severely head-injured patients are hypermetabolic/hypercatabolic and exhibit many aspects of the postinjury acute-phase response. These patients have hypoalbuminemia, hypozincemia, hypoferremia, hypercupria, fever, and increased synthesis of acute-phase proteins such as ceruloplasmin and higher C-reactive protein levels. It has been suggested that increased interleukin-1 (IL-1) in the ventricular fluid may be responsible, at least in part, for these metabolic abnormalities. In the present study, serum albumin levels were evaluated throughout an 18-day study period in 62 head-injured patients receiving aggressive nutritional support. Hypoalbuminemia (mean +/- standard error of the mean 3.10 +/- 0.2 gm/dl; normal value 3.5 to 5 gm/dl) was observed upon hospital admission; these albumin levels continued to decrease until 2 weeks postinjury, despite aggressive nutritional support. This hypoalbuminemia may be mediated via altered endothelial permeability properties due to endothelial cell dysfunction caused by cytokines such as IL-1. Transendothelial movement of albumin was assayed using a pulmonary artery endothelial cell culture system. Both a crude macrophage supernatant derived from a murine P388D cell line having IL-1 activity (mIL-1) and human recombinant IL-1 (rIL-1) were tested. The amount of albumin transferred was time- and concentration-dependent, with maximal transfer at 24 hours and 20 U of mIL-1 per 0.5 ml of culture medium. Endothelial permeability changes observed after incubation with mIL-1 were confirmed using rIL-1. Compared to control cultures, 20 U of rIL-1 and 20 U of mIL-1 increased albumin transfer across endothelial monolayers 205% and 459%, respectively. These findings suggest that the mechanism of hypoalbuminemia seen after severe head trauma can be explained in part by IL-1-induced endothelial cell injury, resulting in enhanced endothelial permeability to albumin.
authors.affiliation: Department of Medicine, University of Kentucky, Medical Center, Lexington.
authors.forename: C J
authors.initials: CJ
authors.lastname: McClain
authors.forename: B
authors.initials: B
authors.lastname: Hennig
authors.forename: L G
authors.initials: LG
authors.lastname: Ott
authors.forename: S
authors.initials: S
authors.lastname: Goldblum
authors.forename: A B
authors.initials: AB
authors.lastname: Young
mesh_terms: D001930:Brain Injuries / Q000097:blood / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000032:analysis; D002463:Cell Membrane Permeability; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D007958:Leukocyte Count; D012709:Serum Albumin / Q000378:metabolism*; D015032:Zinc / Q000097:blood
chemical_list: D007375:Interleukin-1; D012709:Serum Albumin; D002097:C-Reactive Protein; D015032:Zinc