Metabolic Response to Trauma

Metabolic Response to Trauma

• The body responds to trauma with a cascade of physiological reactions to contain, heal tissue damage, and protect itself.
• This response is similar across various traumas, including fractures, burns, sepsis, and surgery.
• The response's extent is proportional to the trauma's severity, pain, and arising complications
• Hosts adapt homeostatic responses following burns, sepsis, surgery, or trauma to restore the body to its pre-injury state.

Phases of the Response

• The unmodified response includes the "ebb" and "flow" phases.
• The Ebb phase has a reduced energy expenditure period that lasts 24-48 hours.
• The Ebb phase is characterized by rises in catecholamines and cortisol, and a fall in plasma Insulin level.
• The patient is cold and hypotensive during the Ebb phase, it is reversible through resuscitation.
• The Catabolic flow phase includes increased metabolism, -ve nitrogen balance, hyperglycemia, increased heat production, increased O2 consumption, and lean body weight loss.
• The increase in metabolic rate ranges from 10% in elective surgery to 50% in multiple trauma and 200% in major burns.
• This phase can last days or weeks based on injury severity, individual health, and medical intervention.
• The metabolism is less marked in extremes of age or in previously malnourished individuals.
• Once started the process cannot be stopped rapidly.
• Recovery has an anabolic phase with weight gain and restoration of protein and fat stores.
• The anabolic process is slow and prolonged.

Summary of the Phases

• Ebb Phase: triggered by injury, lasts 24-48 hours, presents with hypovolaemia, decreased temperature and CO, decreased BMR, and increased LA. It aims to conserve energy with catecholamines, cortisol, and aldosterone hormones.
• Flow Phase: onset by resuscitation, lasts catabolic 3-10 days and anabolic weeks, characterized by catabolism-increased BM, negative N balance, weight loss and anabolism- protein and fat stores replenished, weight gain. it aims to mobilize energy with catechol, cortisol, and glucagon hormones

Initiation of Response

• Various stimuli can produce a response, where multiple stimuli often produce greater effects than the sum of single responses through synergy.
• Factors include pain, tissue injury, and infection (endotoxins as powerful stimuli for TNF release that can enter circulation via mucosal barrier damage).
• Hypovolemia (hemorrhage, plasma loss, third space loss), starvation, hypoxia, hypercapnia, pH changes, fear, anxiety, emotion, and temperature changes can be factors.

Mediators of Response

• Mediators include sympathetic nervous system response, endocrine response, acute phase protein, and vascular endothelial response, producing intertwined effects.
• Multiple feedback loops prevent excessive activation of inflammatory cascades.

Sympathetic Nervous System

• Stimulated both centrally and peripherally mainly by pain and hypovolaemia.
• This triggers the release of Norepinephrine from peripheral ganglia and Epinephrine from the adrenal medulla.
• Catecholamines prepare the body for fight or flight through cardiovascular, visceral, and metabolic actions.
• Heart rate and myocardial contractility are increased.
• Blood is diverted from the skin and visceral organs to the brain heart and skeletal tx
• Non-essential visceral functions, like intestinal motility, are suppressed, resulting in paralytic ileus; bladder sphincter tone also increases.
• Blood glucose rises due to increased breakdown of liver and muscle glycogen, gluconeogenesis, suppressed insulin secretion, and stimulated glucagon secretion.
• It stimulates growth hormone (GH) and Renin
• Lipolysis in adipose tissue and ketogenesis in the liver are stimulated.

Endocrine Response

• The hypothalamus Pituitary Axis (HPA) involves GH, Arginine Vasopressin (AVP)/ADH, Insulin, and Glucagon, causing changes in carbohydrate and lipid metabolism.
• This response protects against overreacting to the acute phase response.
• HPA is stimulated by the injury itself.
• ACTH is released from the anterior pituitary via neurological stimuli to the hypothalamus and by AVP, angiotensin, and catechols.
• It stimulates the adrenal cortex to produce glucocorticoids and potentiates the effect of catechols on myocardial contractility.
• Glucocorticoids are generally permissive, with increases in trauma being associated with metabolic, cardiovascular, and immunological effects.
• Cortisol is a main glucocorticoid.
• Actions include: catabolic, diabetogenic, maintenance of blood volume, anti-inflammatory, and immunosuppressant.
• Aldosterone increases Na reabsorption and K excretion.
• ADH increases reabsorption of solute-free water, causes peripheral vasoconstriction, and increases glycogenolysis and gluconeogenesis.
• Insulin secretion is initially reduced but increases later from hyperglycemia.
• Glucagon stimulates gluconeogenesis, ketogenesis, and lipolysis.
• GH promotes protein synthesis and breaks down lipid and carbohydrate stores.

Acute Phase Reactions

• Both local and systemic.
• PMNs and monocytes are attracted to the injury site.
• Cells produce cytokine peptides, including IL – 1,2,6, TNF, and IF.
• Actions involve: vasodilatation, increased capillary permeability, cell migration to the wound, activation of coagulant and complement cascades, and proliferation of endothelial cells and fibroblasts.

Systemic Effects

• Cytokine production causes large systemic effects.
• Overflow into systemic circulation is an important factor in SIRS, with high doses of IL1 and TNF leading to MODS.
• Fever, malaise, headache, and myalgia occur alongside vasodilation.
• Others include the activation of immune function by leukocytosis, the release of ACTH and cortisol, the activation of clotting cascades, and a decrease in levels of circulating Fe and Zn.
• Serum levels of acute phase proteins (APPs) are also affected.
• Levels Increased include CRP, fibrinogen, C3, antichymotrypsin, ceruloplasmin, and haptoglobin.
• Decreased levels of albumin and transferrin

Vascular Endothelial Response

• With tissue injury, endothelial cells are activated, leading to neutrophil adherence.
• Vasoactive compounds are released.
• Vasodilators: NO and prostaglandins
• Vasoconstrictors: endothelins and thromboxanes
• PAF causes platelet aggregation through interaction with platelets.
• This may predispose to VTE.

Outcome of Response

• Inflammatory response produces clinically apparent local and systemic effects.
• Local responses are signs of inflammation.
• Systemic Response: Increased ECF volume and hypovolaemia
• Increased vascular permeability and oedema
• Early reduced urine output and increased urine osmolality
• Reduced 'free' water clearance
• Late diuresis and increased sodium loss
• Pyrexia without infection
• Early reduction in metabolic rate
• Late increased metabolism, negative nitrogen balance and weight loss
• Lipolysis and ketosis
• Gluconeogenesis via amino acid breakdown
• Reduced serum albumin
• Hyponatraemia due to impaired sodium pump action
• Acid-base disturbance – usually a metabolic alkalosis or acidosis
• Immunosuppression
• Hypoxia and coagulopathy

Clinical Manipulation of The Response

• The local response to trauma is beneficial.
• The systemic response becomes less as the degree of trauma increases.
• Hospital settings can suppress and control the response.
• In trauma and emergency surgery, pain, bleeding with hypovolemia, hypoxia, and anxiety are managed for some time before surgery.
• Stimuli can be usually controlled to reduce the systemic response.
• This can be achieved PRE OP, INTRA OP, and POST OP

Clinical Manipulation of The Response

• Pre-op: Prompt/adequate resuscitation, fluid + electrolyte replacement + antibiotics, correction of anaemia. Reduce fear/anxiety by explanations + analgesics/anxiolytics

• Intra-op: Control pain w/ analgesics, local or regional before noxious stimuli, choice of anaesthesia-epidural. Correct hypoxaemia/ensure minimal trauma, control infections via pus drainage, antibiotics and selective gut decontamination. Warm environment/fluids/blood

• Post-op: Adequate fluid, electrolytes and nutritional support, Analgesia, early enteral feeding (gut), early ambulation prevents muscle wasting, Immunonutrition (glutamine, arginine and omega 3)

Conclusion

• Although the response has some benefits it is pertinent to closely monitor patients and be anticipatory rather than reactionary in the approach to managing the untoward effects, because once the cascade starts it becomes extremely difficult to curb or reverse.