2.  Introduction  Phases of the Metabolic response  Mechanism/pathway  Principal Responses  Determinants of Magnitude of The Responses  Modification of the metabolic response  Summary/Conclusion

3. INTRODUCTION HOMEOSTASIS- “milieu intérieur” Body injury / stress of any sort alters body homeostasis and is usually accompanied by local and systemic effects aimed to return the body to status quo.

4.  Cascade of physiological events brought into play for the “preservation of self” and homeostasis.  If uncontrolled may become detrimental and increase morbidity.  Seen in trauma, burns, sepsis and surgery etc. Extent of response proportional to severity of insult

5. PHASES The unmodified response divided into two phases the ‘ebb’ & ‘flow’ (Cuthbertson,1930). Ebb phase = survival phase ( few hours after injury.) Reversible by early and prompt resuscitation. Flow phase follows ( only attenuated ) 2 parts – Catabolic  Metabolic rate - (negative nitrogen balance and weight loss. -This phase usually last about a week in mod. trauma usually longer in severe trauma and if sepsis sets in. Anabolic phase - protein and fat stores restoration + weight gain (positive nitrogen balance). -The recovery phase usually lasts 2–4 weeks.

8.  Hemodynamic response  Fluid and electrolyte changes  Altered protein metabolism  Changes in plasma protein  Hypermetabolism  Immunosuppresionn

9.  HEMODYNAMIC RESPONSE  venous constriction  increased rate of the sino-atrial node  More forceful cardiac contraction  Arteriolar constriction  MEDIATED BY cathecolamines, ADH, Aldosterone

10. FLUID AND ELECTROLYTE CHANGES  Renals -↑ H ₂O & Na⁺ Retention(ECF VOLUME EXPANSION) -↑K⁺ Excretion  Intestine -↓absorption of H₂O & K⁺ -↑K⁺ Secretion  Mediated by ADH and aldosteone.

11. ALTERED PROTEIN METABOLISM & N ₂ BALANCE 1. ↑ pro ⁻ turnover: catabolism > anabolism 2.10-15g of N;62.5-96g Pr ⁻ ;or 300-450g of mxl tissue loss Daily, post moderate-severe Ops 3. ↑Muscle Proteolysis due to; -IL-1 (activated macrophages)→ PGE₂ release - TNF -Cortisol,Starvation,Fever & immobilization 4. Proteolysis→↑ br Essential AAs; for Gluconeogenesis & synthesis of Enzymes, Hormones,Plasma pro⁻,Acute phase pro⁻& Collagen for wound healing.

13. 5. Prolonged –ve N ₂ Bal → Hypoproteinaemia →Pulm & Cardiovascular failure,↓ immune fxn & wound healing 6.Infusion of Pro⁻, Epidural Anaesthesia, post Op Analgesia & Laparoscopic surgeries→↓the rate of post Op Catabolism

14. CHANGES IN PLASMA PROTEINS 1. ↑ in P.P-due to liver stimulation by IL-6,4rm activated peripheral monocytes 2.Albumin turnover ↑ ;conc. Falls within 3hrs due to transcapillary migration,reaches lowest in 48hrs & rises slowly in 7-14days 3.Transferin; ↓by 25-30% in 3-6days 4.Acute phase proteins: ↑ ≥25% following trauma & sepsis

15. 1.REE ↑ by 12% for every 1oC rise in temp. 2.Normal REE-6300-7500J/24hrs 3.REE ↑ 10%-major operation,25% -major #,50-80% in sepsis,40-100% in burns 4.Glycogen reserve provides energy 4 the ist 12-20hrs,hence alternative 4rm fats & protein 5.160g of fats & 70g of protein broken down to provide dly energy requirement ; may increase to 250-500g

16. 6.Trigycerides →lipolysis→FFA & glycerol 7.FFA for combustion,glycerol for gluconeogenesis 8.lipolysis-stimulated by catecholamines,glucagon,cortisol,GH.inhi bited by insulin & PG-E 9.Consequences of hypermetabolism-Wt loss,fatigue 10.Wt loss from lipolysis,protein catabolism,diminished food intake

17.  Abnormalities in Macrophages/Monocytes Function 1. ↓ phagocytosis capacity 2.↑ lysosme stability & ↓ oxidative burst 3.Impaired Ag presentation to lymphoctes 4.↓ expression of MHC-II,MHC-I, HLA-A on cell surface 5.↓ production of IL-1,IL-6,IL-12,TNF after initial rise

18.  Abnormalities in Lymphocytes Function 1. ↓T-lyphocytes prolifferation & reduce T4:T8 ratio.normal-2:1 2.↓NK cell activity & lymphokine activated killer cell activity 3.Impaired T4,T8 activity 4.Appearance of immature T cells

19.  Causes of Immunosuppression post- trauma 1.Stress Hormones 2.Prostagladin E2 3. Suppressive active glycopeptides- formed in traumatized pxs 4.peri-op blood transfusion 5.Gut integrity breach

20.  OTHER RESPONSES Pyrexia Insulin resistance Changes in iron and zinc metabolism

21.  Age  Sex  Nutritional state  Magnitude of trauma  Concurrent disease  Environmental Temperature  Treatment(s)

22.  Prompt and adequate blood, fluid and elect replacement  Spinal anaesthesia and analgesia  Minimally invasive surgeries  Antibiotics  Wound debridement and drainage of septic foci  Early enteral feeding

23.  The profound neuroendocrine and metabolic responses to injury,though homeostatic in “intent” can become deleterious if not controlled  Understanding the principles & instituting prompt interventions are important in reducing associated morbidities.