1. The Systemic
Response to Injury
นพ.สมพร สหจารุพัฒน์

2. The Systemic Response to Injury
Neurohormonal Response to Injury
Immune Response to Injury
Other Mediators of Injury
Response
Metabolic Response to Injury

3. Neurohormonal Response to Injury
Hormone Response pathways
Mediators released by injured tissue
Neural and nociceptive input
Baroreceptor stimulation (volume depletion)

4. Hormones Under Anterior Pituitary Regulation
Corticotropin Releasing Hormone
Pain fear anxiety emotional
Neural signal --> paraventricular necleus(hypothalamus) --> CRH
CRH --> ACTH
Most injury -->  CRH, ACTH
Severity of injury
Adrenal gland  --> glucocorticoid

5. Cortisol Glucocorticoids
Major Glucocorticoids
Essential for survival after stress
Persistent elevated (1-4 wk)
Potentiate glucagon and epinephrine
Hyperglycemia (Gluconeogenesis, Proteolysis, Lipolysis)
Hepatic gluconeogenesis
Acute Adrenal insufficiency

6. Thyrotropin Releasing Hormone (TRH) Thyroid Stimulating Hormone(TSH)
TRHTSH  T4  T3 (peripheral tissue)
Increase formation and storage of fat
Cellular metabolism
T3 level after injury
(no rise in TSH release)
 Free T4  High mortality

7. Growth Hormones (GH)
GH (Anterior pituitary) pulsatile (sleeping hours)
Physical exercise, sleep, stress, hypovolemia fasting hypoglycemia (stimuli)
hyperglycemia, hypertriglyceridemia, somatostatin, beta-stimulation, cortisol(inhibit)
Promote protein synthesis
Lipolytic effect
Inhibit insulin release   glucose
GH(injury, major surgery, anesthesia)

8. Endogenous Opioid after major injury
Hormones Under Posterior Pituitary Regulation Arginine Vasopressin (or ADH)
Elevated plasma osmolality
pain and glucose, effective circulating volume
Reabsorption of water (distal tubule)
Vasoconstriction
Persist for 1 week

9. Catecholamines ( ANS) Severe injury--> activate adrenergic system
Norepinephrine and epinephrine
 3-4 เท่า after injury
Liver
Glycogenolysis
Gluconeogenesis
Lipolysis
Ketogenesis
 Glucogon  insulin
Hyperglycemia (cortisol)

10. Aldosterone Adrenal zona glomerulosa
AngiotensinII, hyperkalemia, ACTH (most important)
Maintain intravascular volume
Sodium reabsorption, Excrete hydrogen,potassium

11. Renin Angiotensin Renal juxtaglomerular apparatus
ACTH, AVP, glucagon, prostaglandin, potassium, Mg, Ca
Decrease in blood pressure
Angiotensinogen Angiotensin I Angiotensin II
Potent vasoconstrictor (Angiotensin II)
Stimulate heart rate, myocardial contractility
Maintain volume homeostasis

12. Insulin Pancreatic beta islet cells
Glucose major stimuli insulin release
Epinephrine, glucagon, somatostatin IL-1 inhibit release
Exert anabolic effect - Lipogenesis, protein synthesis
Few hrs after injury   insulin

13. Glucagon Pancreatic alpha islet cells Catabolic role
Contrast effect to insulin

14. Immune response to injury
Small protein, immunocytes
Cytokines
Local cell injury and systemic cell immune
Blinding to specific cell receptors
Influence immune cell production, differentiation, proliferation and survival
Fever, leukocytosis, Alteration of respiratory and heart rates
Multiple organ failure, SIRS

15. Tumor Necrosis Factor-alpha
Monocyte, macrophage and T-cell
Peritoneum and splanchnic tissue
Muscle catabolism and cachexia(stress)
Coagulation activation
Release of PGE2, ; PAF; glucocorticoid

16. Interleukin-1 Interleukin-2 Macrophage and endothelial cells
Febrile response to injury
Anorexia(satiety center)
Interleukin-2
Promote T lymphocyte proliferation immunoglobulin, gut barrier integrity

17. Interleukin-4 B lymphocyte proliferation Antibody mediated immunity
Switch in differentiating B lymphocyte to produce IgG, IgE

18. Interleukin-6
Indicator of SIRS
Predictor of preoperative morbidity

19. Other Mediators of injury response
Endothelial cell mediators
Endothelial cell functions
Modulating coagulation, vasomotor activity
Endothelial Derived Nitric Oxide
Vasodilatory

20. Prostacyclin PAF Endothelium derived vasodilator
Vascular shear stress and hypoxia
PAF
Stimulate production of Tx A2
Potent vasoconstrictor
Glucagon and catecholamine
Hypotension, vascular permeability hemoconcentration

21. Metabolic Response to Injury การตอบสนอง 3 ขั้นตอน
1.Ebb phase
Earliest moments to hours
hemodynamic instability circulating  blood volume
Enhancement of neuroendocrine hormone
Adrenaline
Aldosterone  blood volume
Antidiuretic hormone

22. Reduction in total body energy expenditure
Losses of urinary nitrogen

23. 2.Catabolic phase Effect ของ ADH และAldosterone จากEbb phase
Volume ดีแล้ว  และprocollagen)
Catecholamine, glucagon, ACTH, cortisol hyperglycemia
Metabolic rate 
Nitrogen balance เป็นลม ประมาณ10-25 gm/day
Body weight  gm/day
3-7วันหลังผ่าตัดทั่วไป

24. 3.Anabolic phase Hormone กลับสู่ระดับปกติ Glucose --> energy
Synthesis of fat and protein
Insulin, Androgen
ระยะพักฟื้น(Positive Nitrogen 3-5gm/day)
Weight gain gm/day

25. Metabolic Response to Fasting
A healthy adult of 70 kg body weight
kcal/day(lipid, carbohydrate, protein)
Neurons, leukocytes and erythrocytes (180 gm glucose/day)
 glucose insulin glucagon,GH,catecholamine, angiotensin
Glycogenolysis,Gluconeogenesis
glucose

26. Metabolic After Injury
 energy expenditure,oxygen consumption
 Catecholamine and sympathetic nervous system
Lipid Metabolism
Free fatty acid (principal source of energy)
Lipolysis(Catecholamine )
Ebb phase Lipolysis(  plasma free fatty a and glycerol )

27. Flow phase  Lipolysis
Inhibit fatty a’ synthesis in Ebb และ Flow phase
Ketogenesis is inversely correlated with severity of injury

28. Carbohydrate Metabolism
Systemic glucose intolerance
Macroendocrine hormone(glucagon)
 glucose(severity and survival)
Peripheral insulin resistance, Hepatic glucose production
Inflammatory and healing cells  need glucose

29. Protein and acid Metabolism
ปกติ gm protein or 13-20gm of Nitrogen /day
ปกติ Excretion of Nitrogen 2-3 gm in feces, gm in urine
After injury urine excretion gm urea nitrogen
Decrease in cell mass (skeletal muscle)
Minor injury - protein synthesis
- Normal rate of protein
break down

30. Protein and acid Metabolism
Major injury - net protein catabolism
- Acclerated proteolysis and
gluconeogenesis
Negative Nitrogen balance after injury (peak at first week)
Young healthy male lose protein more than Female,elderly
After injury (Skeletal muscle)
Glutamine energy source of lymphocyte,fibroblast,GI tract
Glutamine essential for gut integrity