homeostatic responses to specific components of injury

8/18/2019 Homeostatic Responses to Specific Components of Injury

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HOMEOSTATIC RESPONSES TO SPECIFIC COMPONENTS OF INJURY

Critical illness creates a variety of comle! interactin" #omeostatic resonses$

T#e clinical feat%res o&serve' are t#e s%m of c#an"es (no)n to occ%r after sin"le

ert%r&ations$ In t#e follo)in" section* events fre+%ently o&serve' in s%r"ical atients are

'isc%sse' as resonses to one sin"le c#an"e$ T#ese a',%stments incl%'e vol%me loss*%n'ererf%sion* starvation* tiss%e 'ama"e* an' invasive infection$

-ol%me .oss$ Ac%te vol%me re'%ction associate' )it# acci'ental in,%ry or an elective

s%r"ical roce'%re is a nonlet#al stim%l%s for t#e mec#anisms t#at maintain circ%lation an'restore &loo' vol%me$ -ol%me loss si"nifies t#e 'ecrease of effective circ%latin" &loo'

vol%me$ T#e most fre+%ent form of vol%me re'%ction in t#e s%r"ical atient is simle

#emorr#a"e$ /it# &loo' loss t#ere is no initial c#an"e in lasma osmolality or tonicity* an'ser%m so'i%m an'0or osmolality remains normal 1t#is is referre' to as isotonic vol%me

re'%ction2$ -ario%s resonses are initiate' after simle vol%me re'%ction* incl%'in" t#e

stim%lation of ressor recetors in t#e arterial tree an' vol%me recetors in t#e #eart$ T#esean' ot#er si"nals lea' to t#e ela&oration of al'osterone an' vasoressin* )#ic# a%"ment

fl%i' retention$In a''ition to t#e #ormonal resonses to a vol%me loss* t#ere is a mar(e' s#ift of fl%i'

across caillary &e's into t#e &loo'stream$ 34 T#is 5refill6 #enomenon 'ecreasesconcentration of re' cells 1as meas%re' &y t#e #ematocrit2 an' may sli"#tly 'il%te t#e ser%m

rotein concentration$ Transcaillary refill is stim%late' &y as little as a 789 to 349 loss in

&loo' vol%me an'* )it# ot#er mec#anisms* re+%ires a&o%t 3: #o%rs to restore &loo'vol%me$

In a''ition to t#e #ormonal resonses to a vol%me loss* t#ere is a mar(e' s#ift of fl%i'across caillary &e's into t#e &loo'stream$ 34 T#is 5refill6 #enomenon 'ecreases

concentration of re' cells 1as meas%re' &y t#e #ematocrit2 an' may sli"#tly 'il%te t#e ser%m

rotein concentration$ Transcaillary refill is stim%late' &y as little as a 789 to 349 loss in &loo' vol%me an'* )it# ot#er mec#anisms* re+%ires a&o%t 3: #o%rs to restore &loo'vol%me$

In a''ition to #emorr#a"e* vol%me re'%ction occ%rs &y ot#er mec#anisms$ T#ere may &e

ac%te 'esaltin" )ater loss associate' )it# vomitin"* 'iarr#ea* ancreatic fist%la*%ncontrolle' ileostomy loss* or intestinal o&str%ction$ In t#ese cases* t#ere is minimal loss

of re' cell mass &%t often a 'ecrease in tonicity after mo&ili;ation of cell )ater* )#ic# is

relatively free of so'i%m$ If osmotic c#an"es in t#e lasma are mar(e' &eca%se of loss ofso'i%m* t#e lasma electrolyte alterations &ecome +%ite 'istinct from t#ose of isotonic

vol%me re'%ction* as seen )it# mil' to mo'erate #emorr#a"e$

Fl%i' losses may also ca%se t#e 'esiccation


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flo) state* o!y"en 'elivery is ina'e+%ate for o!y"en 'eman's of t#e tiss%es 'esite

comensatory mec#anisms* an' cell 'eterioration occ%rs$ Ina'e+%ate erf%sion ca%sesacc%m%lation of aci' ro'%cts* artic%larly lactic aci'* )it#in t#e &o'y* an' t#is is

associate' )it# rofo%n' aci'osis of &ot# t#e intracell%lar an' e!tracell%lar fl%i'

comartments$ Comensatory a',%stments are stim%late' &y t#e (i'ney an' resiratory

tract$ Ho)ever* )it# %n'ererf%sion* minimal +%antities of %rine are e!crete'* an' t#is*accomanie' &y t#e resence of a&normal i"ments in t#e lasma s%c# as #emo"lo&in or

myo"lo&in* may ca%se ac%te renal fail%re$ If a lo)eca%se car&o#y'rate stores are limite' an' &eca%se t#ese "lyco"en stores are %se' rai'ly

after stress* an on"oin" s%ly of "l%cose m%st &e rovi'e'$ S(eletal m%scle roteolysis rovi'es amino aci's t#at serve as "l%cose rec%rsors* alt#o%"# "lycerol from tri"lyceri'e

&rea('o)n may also &e %se' as a car&on so%rce for ne) "l%cose$ 8 @l%coneo"enesis res%lts

an' is "enerally roortional to t#e roteolysis an' increase' loss of %rea in t#e %rine$

Tiss%e =ama"e$ Unli(e t#e resonses to simle starvation* )#ic# are c#aracteri;e' &y a"enerali;e' 'ecrease in meta&olism* in,%re' atients 'emonstrate #ei"#tene' meta&olic

resonses$ T#ese stem from t#e increase' ela&oration of cata&olic #ormones t#at stim%late

resiration* car'iac o%t%t* an' mo&ili;ation an' %tili;ation of f%el$ All t#e rocessescontri&%te to t#e accelerate' loss of &o'y tiss%e$ T#is resonse is c#aracteri;e' &y increase'

o!i'ation of fat an' mar(e' roteolysis* rimarily in s(eletal m%scle$ -ol%me loss*

%n'ererf%sion* an' simle starvation may &e a''itional comonents of t#is resonse* &%tt#e secific resence of 'ama"e' tiss%e aears to &e t#e initiator of t#is #yercata&olic

resonse$ Tiss%e in,%ry ca%ses afferent nerve si"nals t#at increase ela&oration of


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a'renocorticotroic #ormone 1ACTH2 an' ot#er it%itary #ormones$ Ho)ever* ot#er

s%&stances* s%c# as cell &rea('o)n ro'%cts or me'iators release' '%rin" inflammation*may #ave a''itional meta&olic effects$ Many ne) inflammatory cells aear in t#e )o%n'

soon after in,%ry$ Initially* le%(ocytes re'ominate* &%t later macro#a"es an' fi&ro&lasts

are t#e ma,or cell tyes resent$ T#ese cells release a variety of me'iator s%&stances*

incl%'in" cyto(ines* sol%&le &ioc#emical si"nals t#at infl%ence t#e roliferation*'eveloment* an' f%nction of s%rro%n'in" cells to ai' #ost resistance an' )o%n' reair$

Many of t#ese s%&stances #ave &een i'entifie' an' incl%'e t#e interle%(ins* t%mor necrosis

factor 1TNF2ot# rocesses ca%se fever* #yerventilation*

tac#ycar'ia* accelerate' "l%coneo"enesis* increase' roteolysis* an' liolysis* )it# fat%tili;e' as t#e rincial f%el$ 74 If t#e infection is s%''en an' severe 1s%c# as )o%l' occ%r

)it# 'e#iscence of a colonic anastomosis2* #yotension an' setic s#oc( may res%lt$ It is

no) reali;e' t#at t#e me'iators for all t#ese events are cyto(ines* ro'%cts of t#e #ost?s

o)n cells$ In some cases t#e si"nal t#at initiates t#ese alterations is &acterial en'oto!in* alioolysacc#ari'e ela&orate' &y "ram


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En'ocrine C#an"es an' T#eir Meta&olic Conse+%ences$ Most atients re+%irin" elective

oerative roce'%res are a'e+%ately no%ris#e'$ T#ey fast overni"#t an' receive intraveno%ssol%tion containin" 89 "l%cose$ T#ey t#en receive a "eneral anest#eticB t#e s(in is reare'

an' t#e oerative site 'rae'$ An incision is t#en ma'e$

One of t#e earliest conse+%ences of t#e s%r"ical incision is t#e rise in levels of circ%latin"

cortisol t#at occ%rs )#en afferent nervo%s si"nals from t#e oerative site reac# t#e#yot#alam%s to initiate t#e stress resonse* )#ic# t#en stim%lates t#e ela&oration of

cortisol$ T#is #ormone remains at t)o to five times normal levels for aro!imately 3:

#o%rs after a ma,or oeration$ Cortisol #as "enerali;e' effects on tiss%e cata&olism an'mo&ili;es amino aci's from s(eletal m%scle t#at rovi'e s%&strates for )o%n' #ealin" an'

serve as rec%rsors for t#e #eatic synt#esis of ac%te


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States of S%r"ical Recovery$ T#e erio' of cata&olism initiate' &y oeration* a com&ination

of ina'e+%ate n%trition an' alteration of t#e #ormonal environment* #as &een terme' t#ea'rener"ic


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a'ministere' to atients after elective "astrectomy or colectomy$ 78 T#e s%&,ects receive'

arenteral n%trition containin" 34 calories er ("$ er 'ay an' 7 "m$ rotein er ("$ er 'ay$T#e nine control s%&,ects lost $ ("$ 18$G9 of reoerative )ei"#t2 an' #a' a c%m%lative

nitro"en loss of 3$:$3 "m$ er 'ays$ T#e atients receivin" "ro)t# #ormone lost

si"nificantly less )ei"#t 17$ ("$2 an' nitro"en loss )as D$7$7 "m$ er 'ays 1 $4472

1Fi"$ : Fi"$ :2$ >o'y comositional analysis of ot#er atients receivin" "ro)t##ormone 'emonstrate' si"nificant "ain in lean &o'y mass comare' )it# controls 1Fi"$ :D

Fi"$ :D2$ :

RESPONSES TO ACCI=ENTA. INJURY@eneral Feat%res an' Time Co%rse$ Events t#at occ%r after in,%ry are "enerally "ra'e'

resonsesK t#e more severe t#e in,%ry* t#e "reater is t#e resonse 1Fi"$ : Fi"$ :2$ T#e

resonse "enerally increases %ntil a ma!imal level is reac#e'B severity of in,%ry over an'a&ove t#is level simly ca%ses a ma!imal resonse$

Resonses to in,%ry c#an"e )it# time* an' events occ%rrin" at vario%s oints in time )ere

initially 'escri&e' as erio's of e&& an' flo)$ T#e early #ase 1e&& or lo)


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#as &een 'escri&e' in #%mans$ >ot# "ro)t# #ormone an' ACTH levels in t#e ser%m rise

)it#in 7 #o%r after incision in atients receivin" "eneral anest#esia an' %n'er"oin"c#olecystectomy or in"%inal #erniorr#a#y$ Ho)ever* t#is #ormonal resonse 'i' not occ%r

in atients %n'er"oin" a&'ominal roce'%res )#en ei'%ral &loc(a'e )as emloye' in

con,%nction )it# t#e "eneral anest#etic$ 7 Nerve afferents also aear to stim%late t#e

ela&oration of A=H after tra%ma$ In a''ition* several factors t#at accomany t#e stress ofcritical illnessLrestraint* immo&ili;ation* environmental 'ist%r&ancesLmost li(ely alter

afferent nerve im%lses an' affect t#e resonse to in,%ry$

3$ Fl%i' loss from t#e vasc%lar comartment stim%lates vol%me an' ress%re recetors*initiatin" a series of CNSeca%se loss of fl%i' vol%me after in,%ry is closely relate' to

t#e e!tent of tiss%e 'ama"e* t#ese secific mec#anisms allo) a +%antitative resonse toocc%r after tra%ma 1i$e$* t#e resonse is 'irectly roortional to t#e si;e of t#e in,%ry2$

$ Circ%latin" s%&stances may 'irectly or in'irectly stim%late t#e CNS an' set in motion

t#e in,%ry resonse$ Alterations in ser%m electrolytes* release of cell &rea('o)n ro'%cts*c#an"es in t#e amino aci' attern* an' ela&oration of en'oto!in an' t#e release of

cyto(ines* all ori"inatin" from or a 'irect res%lt of t#e )o%n'* may initiate #omeostatic

a',%stments t#at 'evelo after in,%ry$Si"nal Inte"ration an' Effector Mec#anismsK Role of t#e CNS$ T#e &rain receives a variety

of si"nals t#at stress #as occ%rre' an' inte"rates t#is afferent in%t$ Alt#o%"# t#e

symat#etic nervo%s system is not essential to t#e a'atation to simle starvation* t#e CNSis essential to t#e #yermeta&olic resonse to in,%ryB atients )it# &rain 'eat# an'

associate' soft tiss%e in,%ry faile' to mo%nt a flo)


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concentrations are normal or increase'$ Ho)ever* t#e effects of t#ese elevate' ins%lin

concentrations on eri#eral tiss%es 1s(eletal m%scle an' fat2 are &l%nte'$ T#e ca%se of t#emar(e' ins%lin resistance is relate' to 'iminis#e' foo' inta(e an' an altere' #ormonal

environment t#at e!erts anti


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1"reater t#an 849 of &o'y s%rface area2 'emonstrate restin" meta&olic rates t#at may reac#

t)ice &asal levels$ T#ese rates of #eat ro'%ction in tra%ma atients are contraste' )it#t#ose t#at occ%r in ostoerative atients* )#o rarely increase t#eir &asal meta&olic rate &y

more t#an 749 to 789 after oeration$

Concomitant )it# t#e 'eveloment of #yermeta&olism* t#e tra%ma atient %s%ally

'evelos a 7 to 3 C$ elevation in &o'y temerat%re$ T#is osttra%matic fever is a )elleca%se of t#e ma"nit%'e of t#ese losses an' t#e ro"ressive )astin" of s(eletalm%scle mass an' associate' m%scle )ea(ness* it )as ori"inally #yot#esi;e' t#at t#e

nitro"en loss )as a "enerali;e' an' accelerate' &rea('o)n of m%scle rotein$ .i(e ot#er

resonses* t#e loss of nitro"en after in,%ry is relate' to t#e e!tent of t#e tra%ma &%t also

'een's on t#e a"e* se!* an' revio%s n%tritional stat%s of t#e atient* since t#ese factors#el 'etermine t#e si;e of t#e m%scle mass$

Nitro"en &alance st%'ies 'emonstrate mar(e' ne"ative nitro"en &alance after in,%ry* &%t

t#ese st%'ies reflect only net nitro"en cata&olism an' not t#e a&sol%te rate of nitro"en &rea('o)n$ In normal in'ivi'%als* nitro"en e+%ili&ri%m is maintaine' &y a caref%l &alance

&et)een rates of rotein synt#esis an' 'e"ra'ation$ Ne"ative nitro"en &alance occ%rs if t#e

&rea('o)n rate increases an' rotein synt#esis remains t#e same* or if t#e &rea('o)n rateremains t#e same an' t#e rate of synt#esis 'ecreases 1Ta&le : Ta&le :2$

M%scle is t#e ori"in of t#e nitro"en loss in t#e %rine after e!tensive in,%ry$ Ho)ever* it #as

&een reco"ni;e' t#at t#e comosition of amino aci' effl%! from s(eletal m%scle 'oes notreflect t#e comosition of m%scle rotein$ Alanine an' "l%tamine constit%te t#e ma,ority of

amino aci's release'* )#ereas eac# ma(es % only a&o%t 9 of m%scle rotein$ @l%tamine

is e!tracte' &y t#e (i'neys* )#ere it contri&%tes ammoni%m "ro%s for ammonia

"eneration* a rocess t#at ro'%ces t#e net loss of aci'* an' t#is effect can &e a%"mente' &ya'ministration of "l%cocorticoi's$ 3 @l%tamine is also ta(en % &y t#e "astrointestinal

tract* )#ere it serves as an o!i'ative f%el$ T#e "%t enterocytes convert "l%tamine rimarily

to ammonia an' alanine* an' t#ese t)o s%&stances are release' into t#e ortal veno%s &loo'$T#e ammonia is t#en remove' &y t#e liver an' converte' to %reaB t#e alanine may also &e

remove' &y t#e liver an' serve as a "l%coneo"enic rec%rsor$ After t#e stress of a stan'ar'

laarotomy* "l%tamine cons%mtion &y t#e &o)el an' t#e (i'neys is accelerate'* 3: an' t#ereaction aears to &e re"%late' &y increase' ela&oration of t#e "l%cocorticoi's$ 3

Alt#o%"# s(eletal m%scle releases alanine at an accelerate' rate* t#e "astrointestinal tract

an' (i'neys also accelerate alanine ro'%ction$ T#is amino aci' is e!tracte' &y t#e liver

an' %se' in t#e synt#esis of "l%cose* "l%tat#ione* an' ac%te


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St%'ies #ave &een erforme' to 'etermine t#e sites of "l%cose %tili;ation ro'%ce' &y t#e

liver$ First* "l%cose %ta(e )as meas%re' across in,%re' an' %nin,%re' e!tremities$ Net"l%cose fl%! across %nin,%re' e!tremities )as lo)* s%""estin" t#at fat* not "l%cose* )as t#e

rimary f%el for restin" s(eletal m%scle in t#e osta&sortive state$ Ho)ever* increase'

"l%cose %ta(e occ%rre' across t#e in,%re' e!tremity$ 3 In a''ition* t#e in,%re' e!tremity

release' lar"e +%antities of lactate* )#ic# reresente' as m%c# as 49 of t#e "l%cosecons%me'$ Seciali;e' cells of t#e )o%n' an' inflammatory tiss%e 1fi&ro&lasts*

macro#a"es* le%(ocytes2 %n'er"o anaero&ic meta&olism an' 'emonstrate a lar"e caacity

for lactate ro'%ction$ A''itional meas%rements #ave f%rt#er c#aracteri;e' t#e "l%cose'isosal in restin" atients after in,%ry 1Fi"$ :77 Fi"$ :772$

In a''ition to t#e accelerate' "l%cose flo) t#at occ%rs after in,%ry* t#ere is rofo%n' ins%lin

insensitivity$ T#ese effects 'o not occ%r &eca%se of ina'e+%ate +%antities of ins%lin release'from t#e en'ocrine ancreas* for in most cases #yerins%linemia e!ists$ Ho)ever* similar

effects are o&serve' after alterations in t#e #ormonal environment$ For e!amle* ins%lin<

me'iate' forearm "l%cose %ta(e is mar(e'ly 'iminis#e' in normal s%&,ects after 3 #o%rs

of eine#rine inf%sion$ Similarly* 'ays of "l%cocorticoi' a'ministration 'ecreasesins%lin


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#ysiolo"ic a',%stments* tiss%e erf%sion is maintaine'* )#ic# s%orts t#e increase'

meta&olic 'eman's accomanyin" critical illness$ Increase' s(eletal m%scle roteolysis an'accelerate' "l%coneo"enesis are co%le' resonses t#at also occ%rB t#ese &ioc#emical

alterations rovi'e essential n%trients to s%ort vital or"an f%nction an' )o%n' reair$

An elective or semielective oerative roce'%re in t#e revio%sly #ealt#y atient stim%lates

minor cata&olic c#an"es )#en resent

homeostatic responses to specific components of injury

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