The metabolic response to trauma

The Metabolic Stress Response to Trauma
As a consequence of  modern understanding of the metabolic response ,elective surgical practice seek to reduce  the need for homeostatic response by minimizing the primary insult (minimal access surgery, and stress free perioperative care ) .Homeostasis is the co ordinate physiological process which maintain  most of the steady states of the organism.
Neuroendocrine  response to injury / critical illness is biphasic :
-acute phase:  Characterized by actively secreting pituit and elevated counter –regulatory hormones( cortisol, glucagon, adrenaline). Changes are thought to be beneficial  for short term survival.
- chronic phase : Associated with hypothalamic suppression and low serum levels of the respective target organ hormones. changes contribute to chronic wasting.
The innate immune system (principally macrophages  ) interacts in a complex manner  with the adaptive immune system (T cells ,B cells in co generating the metabolic response  to injury.
The metabolic stress response to surgery and trauma: the Ebb and Flow ‘ Model
In the natural world , if an animal is injured, it displays  a characteristic  response which includes immobility, anorexia and catabolism; these changes are designed to aid survival of moderate injury in the absence of medical intervention.
The ebb phase begins at the time of injury and last  24-48 hrs it may be attenuated by resuscitation. but not completely abolished.
The Ebb phase is characterized by hypovolemia, decreased basal metabolic rate, reduced cardiac output ,hypothermia and lactic acidosis. The predominant hormones regulating the Ebb phase are catecholamines,cortisol and aldosterone (following the activation of the rennin- angiotensin system). The magnitude of this neuroendocrine response depends on the degree of blood loss and the stimulation of somatic afferent nerves at the site of injury. The main physiological role of the ebb phase is to conserve both circulating volume and energy stores for recovery and repair.
Following resuscitation. ,the ebb p.  evolves into a hypermetabolic flow phase. which correspond to the SIRS. This phase involves the mobilization of body energy for  hormones recovery and repair and the subsequent replacement of lost or damaged tissue.
It is subdivided into a- initial catabolic phase ,lasting 3- 10 days , followed by anabolic phase which may last for weeks if excessive recovery and repair are required following serious injury.
Changes in body composition following injury :The average 70-kg male consist of 13 kg fat,and fat-free mass i.e  the lean body mass : 57 kg). in such individual the lean tissue is composed primarily  of  protein 12 kg ,water 42 kg and minerals 3 kg.
The protein can be considered as 2 basic compartments, skeletal muscle 4 kg and non skeletal muscle 8 kg which include the visceral protein  mass.  The water mass 42  l iter is  divided into  intracellular 28 and extracellular 14 liter. Most of the mineral mass is contained in the bony skeleton (fig 1-7).
The main labile energy reserve in the body is fat ,and the main labile protein reserve is skeletal muscle .while fat muscle mass can be reduced without major detriment to function, loss of protein mass result not only in skeletal muscle wasting ,but also depletion of visceral protein status. Within lean tissue ,each 1 gm of nitrogen is obtained within 6.25 gm of       protein, which is contained in 36gms of wet weight tissue. Thus the loss of 1gm of  nitrogen in urine is equivalent to the breakdown of 36 gms of wet weight lean tissue  . Protein turnover in the whole body is of the order  of 150- 200gm/day.   A normal human ingest  70-100 gm protein /day  which is metabolized and excreted in the urine as ammonia and urea (14gm N/d ).
During total starvation ,urinary loss of nitrogen  is rapidly attenuated by a series of adaptive changes. Loss of body weight follow a similar course.
Critically ill patients admitted  to ICU with sever sepsis   or major blunt trauma  undergo massive changes in body composition. Body weight increases  immediately on resuscitation with an expansion of extracellular water  by 6-10 liter within 24hrs. Thereafter ,even with optimal metabolic care  and nutritional support, total body protein will diminish by 15% in the next 10 days. and body weight will reach negative balance as the expansion of the extracellular space resolves .To maintain body weight and nitrogen balance following elective surgery; this can be achieved by blocking the neuroendocrine stress  response with epidural analgesia and providing early enteral feeding .Moreover, the early fluid  retention ph. can be avoided by careful intraoperative management of fluid balance ,with avoidance of excessive administration of intravenous  saline.
Avoidable factors that compound the response to injury (fig 1-10)
1-continued haemorrhage 2-hypothermia 3-tissue edema4- tissue underperfusion 5- starvation  6-immobility.
Volume loss:
During simple hemorrhage ,pressor receptors in the carotid artery and aortic arch ,and volume receptors in the wall of the left atrium, initiate afferent nerve input to the CNS resulting in the release of both aldosterone and ADH. pain can stimulate  ADH release.ADH acts directly on the kidney to cause fluid retention. Decreased pulse pressure stimulates the juxtaglomerular apparatus in the kidney and directly activates the renin  angiotensin system, which in turn increases aldosterone release . aldosterone causes the renal tubule to reabsorb sodium (and consequently conserve water).ACTH release also augments aldosterone respose. The net effect of aldosterone and ADH result in the natural oliguria observed after surgery and conservation of sodium  and water in the extracellular space.The tendency towards water and salt retention is exacerbated by resuscitation with saline rich fluids.Salt and water retention can result in not only peripheral oedema, but also visceral oedema (stomach ).Such visceral oedema has been associated with  reduced gastric emptying, delayed gastric emptying, delayed resumption of food intake and prolonged hospital stay. Careful limitation of intraoperative administration of colloids and crystalloids(Heartman;s solution)so there is no net weight gain following elective surgery has been proven to reduce postoperative complications and length of stay.
Hypothermia: it result in increased elaboration of adrenal steroids and catecholamines. When compared with normothermic controls, even mild hypothermia result in a two to threefold increase in postoperative cardiac arrhythmias and increases catabolism. Randomised trials have shown that maintaining normothermia by an upper body forced –air heating cover reduces wound infections, cardiac complications and bleeding and transfusion requirements.
Tissue oedema :                                                                                                                                                                      During systemic inflammation, fluid, plasma proteins, leucocytes,macrophages and electrolytes leave the vascular space and accumulate in the tissues.This can diminish the alveolar diffusion of oxygen & may lead to reduced renal function. Increased capillary leak is mediated by a wide variety of mediators including  cytokines,prostanoids,bradykinin and nitric oxide. Vasodilitation implies that intravascular volume decreases, which induces shock if inadequate resuscitation is not undertaken. Meanwhile ,intracellular volume decreases, and this provides part of the volume necessary  to  replenish  intravascular and extravascular  extracellular volume. Systemic inflammation and tissue underperfusion
The vascular endothelium controls vasomotor tone  and microvascular flow, and regulates trafficking of nutrients and biologically active molecules. When endothelial activation is excessive ,compromised microcirculation and subsequent cellular hypoxia contribute to the risk of organ failure.
Maintaining normoglycemia  with insulin infusionduring critical illness may protect the endothelium.
Adminstration of activated protein C  to critically ill patient s reduce organ failure  and death possibly ;in part, by  preservation of the microcirculation in vital organs.
Starvation :
During starvation ,the body is faced with obligate need to generate glucose to sustain  cerebral  energy metabolism (100gm of glucose/day).This achieved during 1st 24hrs  by mobilizing glycogen  stores  and thereafter by hepatic gluconeogenesis  from aminoacids ,glycerol and lactate. The energy metabolism of other tissues is sustained by mobilizing fat from adipose tissue.such fat mobilization is mainly dependent  on a fall in circulating insulin levels. Eventually ,accelerated loss of lean tissue (the main source of aminoacids  for hepatic gluconeogenesis ) is reduced  as result  of the liver converting free  fatty acids  into ketone bodies,which can serve as substrate  for glucose for  cerebral energy  metabolism.
Prevent unnecessary aspects of the surgical stress responseA- Minimal excess techniques. B-Blockade of afferent painful stimuli (epidural analgesia )    c-  minimal period of starvation     d- early mobilization.

Homeostasis is the foundation of normal physiology.
Stress –free perioperative care helps to restore homeostasis following elective surgery.
Resuscitation ,surgical intervention and critical  care can return  the severely injured patient  to a situation in which homeostasis becomes possible once again.
Neuroendocrine  response to injury/ critIcal illness:
a- Acute phase :characterized by actively secreting pituitary and elevated counter –regulatory hormones (cortisol, glucagon, adrenaline). Changes are thought to be beneficial for short term survival.
b- Chronic phase associated with hypothalamic suppression and low levels of the respective target organ hormones. Changes contribute to chronic wasting.
Systemic inflammatory response  syndrome SIRS following major injury:
-is  driven initially by pro inflammatory cytokines  ( IL1,IL6,TNFa)
- it is followed by increased plasma levels of cytokine antagonists and soluble receptors. (IL-1Ra,TNF-Sr )
-if prolonged or excessive may evolve into a counter –inflammatory response syndrome SIRS.
Purpose of neuroendocrine changes following injury
Acts to -   provide essential nutrients substrates for survival
-  Postpone anabolism                                     - Optimise host defence
Changes in body composition following major surgery / critical illness
- Catabolism leads to a decrease in fat mass and skeletal  muscle masss
- -Body weight  para-Body weight  paradoxically increase  because of expansion ofextracellular space.
A protective approach to prevent unnecessary aspects of the surgical stress response :.
-Minimal excess techniques   -blockade of afferent painful stimuli(epidural  analgesia )
-minimal periods of starvation .
-early mobilization.