The Systemic Response to Injury นพ.สมพร สหจารุพัฒน์

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

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

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

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

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

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)

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

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

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

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

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

Glucagon Pancreatic alpha islet cells Catabolic role Contrast effect to insulin

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

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

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

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

Interleukin-6 Indicator of SIRS Predictor of preoperative morbidity

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

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

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

Reduction in total body energy expenditure Losses of urinary nitrogen

2.Catabolic phase Effect ของ ADH และAldosterone จากEbb phase Volume ดีแล้ว  และprocollagen) Catecholamine, glucagon, ACTH, cortisol hyperglycemia Metabolic rate  10-100 Nitrogen balance เป็นลม ประมาณ10-25 gm/day Body weight  200-800 gm/day 3-7วันหลังผ่าตัดทั่วไป

3.Anabolic phase Hormone กลับสู่ระดับปกติ Glucose --> energy Synthesis of fat and protein Insulin, Androgen ระยะพักฟื้น(Positive Nitrogen 3-5gm/day) Weight gain 200-300 gm/day

Metabolic Response to Fasting A healthy adult of 70 kg body weight 1700-1800 kcal/day(lipid, carbohydrate, protein) Neurons, leukocytes and erythrocytes (180 gm glucose/day)  glucose insulin glucagon,GH,catecholamine, angiotensin Glycogenolysis,Gluconeogenesis glucose

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 )

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

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

Protein and acid Metabolism ปกติ80-120 gm protein or 13-20gm of Nitrogen /day ปกติ Excretion of Nitrogen 2-3 gm in feces, 13-20 gm in urine After injury urine excretion 30-50 gm urea nitrogen Decrease in cell mass (skeletal muscle) Minor injury - protein synthesis - Normal rate of protein break down

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