CKI I ICAL
CARE
CLINICS
CI I[ ('ale
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'11112 I (2005) 177
I'M
Epithelial Barrier Dysf~~nction:
A Unifying
Theme to Explain the Pathogenesis of Multiple
Organ Dysfilnction at the Cellular Level
Mitchell P. Fink, MD"."'", Russell L,. Delude, PIID"'"
The multiple organ dysti~nctionsyndrome (MODS) is the most comlnon cause
ol'death among patients requiring care in an ICIJ. There is widespread agreelneni
~ h a MODS
l
is the clinical manifestation of a dysregulated inlla~zzrnaloryresponse.
Indeed, lnost of the published research regarding the pathogenesis of MODS has
focused on the various signaling pathways that lead to the activation of the innate
immune system and the claboralion of cytokines, oxidants, dss~re-desll.irctive
enzymes, and other prointlammatory mediators (Fig. I, steps 1-3). Interestingly,
and cell biologic hasis for organ tlysfilnctio~l1x1. se
however, the hioclle~r~ical
(Fig. I, step 4) remains very poorly ~ i ~ ~ d e r s t o oAs
d . is emphasized taler., the
histopathology of MODS in humans is remarkably bland; ~ilassivecell deal\),
whether caused by necrosis or apoptosis, is almost certainly not the cause of
MODS. Rather, the final step in the development of MODS is 1,rol)al)ly the
w~despreaddysfunction of parenchy~nalcells in ~ ~ r u l t i p lorgans
e
as a result o f
the deleterious erfects of a poorly controlled systelnic i11tlam111aLoryresponse. A
hugely l~nderexploredarea o f research can I)e suni~iiarizedby this questiorr: Flow
does the intlammato~yresponse lead to cellular dysfi~nctionthat translates into
dysiilnction of those organs (ie, the lungs, liver, kidneys, and intestine) that are
--
*
-
auil~or.Depol-t~nenlof Cl-ilical Care tvlctlici~~c,
t Ini\,ersity of I'it~shurgh S c l ~ o o l
o f MC~IC~IIS,6th Scaife i l u l l , 3550 Terrace Street, I'i(tsburgll, ['A 15261
- n i l u I / t e : fir1krnp(r~!~~c~11.~~~11ic.e~111
(M.1' Fink)
( 'ol-rssponding
0739-070410518: sce hunt mattel- '02005 Elsevier lnc A l l rights rcsel-vecl.
-
tlui: l0.1016/j.ccc.2005.0I .ti05
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