Systemic inflammatory

response to injury
SIRS
BY
Dr. A . Aljohari
assistant professor general surgery
K.A.U.H
Introduction

* injury initiates a sequences of responses that is both the

results of the injury and the mean by which the organism
survives and heals.

* the results of these responses are maintenance of the blood

flow , O2 delivery and organ perfusion with mobilization and
use of substrates for healing and recovery

* the term injury includes any traumatic event

* elective surgery
* motor vhicle accedent
•The biological response are the same but the magnitude of
the response will vary according to the severity of the injury .

* the response :
* neuroendocrine
* inflammatory
* metabolic
The phase of injury :

1- injury phase 2- turning point

3- anabolic phase 4 – late anabolic

The injury phase:

begins at the time of injury lasts for 2_5 days or longer. The
duration is related to the magnitude of the injury and the
presence or absence of complications.

Numbers of stimuli trigger the biological response to injury

tending to rests the hemeostasis at a higher metabolic and
circulatory rates and a higher level of functioning.
Factors and stimuli that can trigger the systemic
response :

* minor
pain , fear ,fatigue
anaethesia , drugs
immobilization
transient starvation

* moderate :
pain , anexiety
anaethesia , drugs
tissue injury , infection
blood or body fluid loss
•Sever
multisystem injury
tissue necrosis
major burn
sepsis
shock
prolonged starvation
The response :
@ afferent pathway

@ efferent pathway

The afferent pathway:

the stimuli of the injury provide neuronal and mediator

signals to the CNS primarly by nociceptors , baroreceptors

chemreceptors , and other mediators from the wounds

Shortcut to scan0001.lnk
The wound hormones :

* they provides afferent stimuli to the CNS and other systems

as an independent organ.

* they initiates many of changes of the metabolic response by

signals come from a variety of mediators produced by cells in
the wound ( PMN , monocytes , macrophages , endothelial ).

* the mediators constitute the factors of the inflammation

particularly cytokines
* autocrine activity
* paracrine activity
The efferent pathway / neuroendocrine response :

the injury phase begins with the stress response and multiple
neuroendocrine alterations and avtivities in the hypothalamic
pituitary adrenal axis

circulatory level of endorphins ( opioids ) rises after injury or

operation as 72 hr .they produce some analgesic and calming
effect , and they also modulate noxious stimuli and
sympathetic response .

B endorphins may contribute to hyperglycemia and glucose

intolerance after injry
The major hormonal changes and the systemic
effect :
The physiological effects :

CVS
maintenance of the BP by vasoconstriction , increase
in the SVR , HR , and CO with shift of the blood volume
from the splanchnic bed to the vital organs

water and electrolytes

ALDOSTERONE
increase in Na reabsorption
increase in K , H+ excretion
small urin volume with high acidity
metabolic alkalosis
ADH
increase in water retension
relative oliguria
The immunological system :

* the SNS , hypothalamic pituitary adrenal system along with

the pathological stress and the neuruondocrine response
produce immunomodulation.

cell mediated immune response :

* it is suppressed after injury due to poduction of the

glucocorticoids that adversely affect cell nuclear cleavage
and inhibition of IL 2 production and T cell proliferation.

* PGE 2 also decreases IL 2 production and lymphocytes

stimulations

* increased production of the cytokines , interferon , IL 12

a,TNF , activates the macrophages and the cytotoxic cells
The humoral response :

* increased production of IL 4 , 5 , 6 , 10 , 13 and the Ab will

down regulate the cellular immunity but augment the humoral
immunity

injury or trauma also reduce expression of the class 2 major

histocompatibility complex molecules HLA-DR

the nonspecific immune system also is activated by increase

in the activity of PMN c
Altered metabolism :

catecholamines and insulin are the key factors in the

production of the following metabolic results :

* enhanced hepatic glycogenolysis and gluconeogenesis.

* reduced insulin secretion and inhibition of his tissue effect

that blocks cellular utilization of glucose.

* stimulation of glucagon secretion with further enhancement

of glycogenolysis and gluconeogenesis.

* catecholamines and glucagon stimulate lipolysis with

release of the fatty acids that provide the major energy
source for the peripheral tissues.
•Break down of the muscle protein produces the a.a , as the
maine substrate for gluconeogenesis.

* increase in ACTH release induce poroduction of the gluco-

corticoids , cortisol , that enhance both gluconeogenesis
and the protein break down.

* there is increase in the secretion of both GH and thyroid

hormones which inhibit the effect of insulin and promot
catabolism.

CHO metabolism :
* hyperglycemia
* pseudodiabetic state
* increase in insulin resistance
Protein metabolism :
increase in skeletal muscle destruction.
negative nitrogen balance.

Lipid metabolism :
lipolysis
ketogenesis with protein conservation.

Hypermetabolism :
increase in heat production , body tempratue and
O2 consumption.
Increase in the resting energy expenditure rate
according to the magnitude of the injury.
Turning phase :

if the pt is adequately stabilized :

* sessation of the neuroendocrine stimulation.
* corticosteroids withdrawal
* decrease of the inflammatory response.
* less likely to develop complications and more likely to
survive.

It is a transitional phase , that may occurs suddenly and

dramatically overnight or may lasts 1-2 more days or longer.

If the pt was not stabilized :

the turning phase will be delayed and the injury phase will
continues.
The anabolic phase :

* gain in the muscular strength

.
* positive nitrogen balance.

* lasts for 3-13 weeks or longer.

* need good nourishment either enteral or parentral

.
Late anabolic phase :

* positive caloric balance .

* gain in weight and body fats.

* lasts for months to years.

How to decrease the response to injury :

* pain relief
* adequate fluid replacement
* treatment of the infection
* careful surgical technique
* minimal surgical procedures
* type of the anaethesia
* maintenance of normothermia
* nutritional support
Systemic inflammatory response and multiple organ
dysfunction MODS:

mods results when major physiological insult could lead to

failure of one or more organ remote from the initiating
disease process which initiated by a range of adverse events
such as trauma , ischemia or infection.

The sequence of failure of individual organs often follows

a predictable pattern with pulmonary failure occuring first as
( ARDS ) , followed by hepatic , intestinal , renal and finally
cardiac.

The mortality of MODS is directly related to number of organ

that fail
one organ …. 40%
two ….. 60%
three …… > 90%
The pathophysiology :

following initial tissue injury , a local inflammatory response

occurs with cytokines induction with resultant endothelial activation and
expression of intracellular adhesion molecules.

activation of both the complement and the coagulation systems with

ampilification of the primary inflammatory response.

Disordered hemodynamics and impairment of the tissue oxygenation with

end results of microvascular and mitochondrial changes that leads
eventually to the organ failure
.
mediators:
TNF
IL 1, 2 ,6
PLT activating factors
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