General Responses to Injury and Acute Illness

16a - General response to injuries and acute illness
The metabolic response is a complex interaction between many body systems
 * Acute inflammatory response
 * The endothelium and blood vessels
 * Afferent and sympathetic NS activation
 * Endocrine response

Acute inflammatory response:
 * inflammatory cells (macrophages and neutrophils) and cytokines (IL8, TNFa, IL1, IL6) are mediators
 * physical damage to tissue results in local activation of those mediators
 * important determinant of the effects of the inflammatory response is whether the effects of mediators remain localized or generalized
 * cascade of events result in rapid amplification of stimuli -> within hours, large number of mediators present at injured site -> controlling and mediating inflammatory response
 * proinflammatory substances : leucocyte, prostaglandins, kinins, complement, proteases, free radicals
 * anti-inflammatory : antioxidant (glutathione, vitamin A&C, protease), protease enzyme inhibitor (alpha-microglobulin), IL10

The endothelium and blood vessel:
 * leucocyte accumulation -> adherence -> migration from blood vessel to injured area
 * mediated by integrins and intercellular adhesion molecule (ICAM) family
 * tissue injure increases the blood flow due to vasodilation -> step up the local delivery of inflammatory cells, oxygen and nutrient
 * vasodilation mediated by kinins, prostaglandins, and NO
 * capillaries in injured site become more permeable to plasma due to increases the size of intercellular pores -> fluid and colloid particles (albumin) leak -> edema
 * tissue factor is exposed -> promote coagulation -> decrease hemorrhage

Afferent and sympathetic NS activation:
 * impulse generated mediates the metabolic response to injury
 * pain fibres (unmyelinated C fibres and myelinated A fibres) are activated
 * stimulated by direct trauma or nerve stimulant (prostaglandins)
 * impulses reach thalamus via dorsal horn of spinal cord and lateral spinothalamic tract -> stimulating:
 * 1) sympathetic NS – tachycardia, increase cardiac output, increase adrenaline, noradrenaline -> change in carbohydrate, fat and protein metabolism
 * 2) stimulation of pituitary hormone release

The endocrine response:
 * this takes place as direct stimulation from respective glands or due to normal negative feedback mechanism
 * helps in maintaining the body fluid’s balance and in the changes to substrate metabolism that occur following injury
 * eg: increase secretion of GH, ACTH, ADH, adrenalin, cortisol, glucagon, rennin, angiotensin
 * eg: reduce in insulin, testosterone, estrogen, thyroid hormone

Consequences of metabolic response to injury:
 * hypovolemia
 * increased energy metabolism and substrate cycling
 * catabolism and starving
 * changes in RBC synthesis and blood coagulation

Hypovolemia:
 * due to fluid loss (hemorrhage, vomiting, sweating, evaporation from exposed organ during surgey) fluid sequestration (third space loss) – leakiness of endothelium
 * body attempts to restore normal fluid status and maintain perfusion to vital organs by fluid and flow-conserving measures
 * fluid-conserving : neuroendocrine response - increase ADH and aldosterone duration of increased usually 48-72 hours
 * blood-conserving :
 * 1) by reduced cardiac output -> decrease blood flow to organ
 * 2) Increase energy metabolism and substrate cycling:

Physical work:


 * physical work usually decreased because of inactivity, although heart and respiratory muscle work may increase resting energy expenditure increased by up to 50% following severe injury as a result of metabolic changes
 * thermogenesis:
 * 1) patient frequently midly pyrexial for 24-48 hours following injuries
 * 2) IL1 resets the temperature-regulating centre
 * 3) pyrexia may also complicate infection occurring after injury
 * 4) metabolic rate increases by 6-10% for each 1`C change in body temp


 * basal metabolic rate:
 * increased activity of protein, carbohydrate and fat related pathways

Catabolism and starvation: - catabolism: breakdown of complex substrate to form simpler molecules


 * carbohydrate – increase glycogenolysis, hepatic gluconeogenesis, insulin resistance tissue, hyperglyceamia
 * fat – increase lipolysis, FFA used as energy substrate, FFA to ketones, glycerol to glucose
 * protein – increase muscle breakdown, AA converted to glucose, negative nitrogen balance

- starvation: inadequate intake of food to meet metabolic demand
 * acute
 * 1) metabolic changes that preserve the glucose supply to brain glycogenolysis, lipolysis


 * chronic
 * 1) accompanied by muscle breakdown to release AA
 * 2) gluconeogenesis in liver
 * 3) FFA converts to ketone

Tissue energy supply in the form of glucose, FFA and ketones Brain adapts to utilize ketone as primary energy substrate - these two processes generally occur simultaneously

Changes in RBC synthesis and blood coagulation:
 * anemia is common after major surgery or trauma due to bleeding and the hemodilution
 * bone marrow production of new red cells is impaired – low erythropoietin, chage in iron metabolism and decrease iron availability
 * blood becomes hypercoagulable – transient for 1-2 days -> increase risk of thromboembolism

contributing factor:
 * endothelian injury activation of coagulation pathway
 * increase activation of platlets
 * dehydration and/ reduce venous blood flow due to immobility
 * increase circulating of pro-coagulant and decrease anticoagulant

Factors associated with the magnitude of metabolic response to injury:
 * patient related :
 * genetic predisposition
 * coexisting disease
 * drug treatments
 * nutritional status

acute surgical/trauma-related :
 * 1) severity of injury
 * 2) nature of injury
 * 3) ischemic-reperfusion injury
 * 4) temperature infection
 * 5) anaesthetic technique


 * Principles & Practice of Surgery – Chapter 1, principle of Surgical Care, page 2