The major hormonal changes and the systemic effect :

1. Systemic inflammatory response to injury SIRSBY Dr. A . Aljohariassistant professor general surgery K.A.U.H

2. 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

3. 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

4. The phase of injury :1- injury phase 2- turning point 3- anabolic phase 4 – late anabolicThe 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.

5. 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

6. Sever multisystem injury tissue necrosis major burn sepsis shock prolonged starvation

7. The response : @ afferent pathway @ efferent pathwayThe afferent pathway:the stimuli of the injury provide neuronal and mediatorsignals to the CNS primarly by nociceptors , baroreceptorschemreceptors , and other mediators from the wounds

9. 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

11. The efferent pathway / neuroendocrine response :the injury phase begins with the stress response and multiple neuroendocrine alterations and avtivities in the hypothalamicpituitary adrenal axiscirculatory 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

14. The major hormonal changes and the systemic effect :

15. 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 organswater 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

16. 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

17. 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 immunityinjury or trauma also reduce expression of the class 2 major histocompatibility complex molecules HLA-DRthe nonspecific immune system also is activated by increase in the activity of PMN c

18. 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.

19. 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

20. 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.

21. 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.

22. 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.

23. 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

24. 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 eventssuch as trauma , ischemia or infection.The sequence of failure of individual organs often followsa 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%

25. 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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