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Surgical Physiology of Trauma
Surgical Physiology of Trauma From the Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois
JOHN H. SCHNEEWIND, M.D., F.A.C.S. Associate Professor of Surgery, University of Illinois College of Medicine; Chief of Emergency Service, Research and Educational Hospitals; Assistant AUending Surgeon, Presbyterian-St. Luke's Hospital; Associate Surgeon, Cook County Hospital
PHYSIOLOGICAL RESPONSE TO INJURY AN UNDERSTANDING of the complicated response of the body to stress, fear or actual organic injury is required for the proper management of the acutely injured patient. These changes are regulated chiefly by the endocrine system mediated through the autonomic nervous system. It appears that stress or injury stimulates increased secretion of epinephrine from the adrenal medulla into the blood stream with activation of the anterior pituitary and liberation of adrenal corticotropic hormone. The result is an immediate increase in output of hormones of the adrenal cortex. These rapid increases have been documented by studies of blood levels of steroids immediately following trauma as well as measurement of the urinary steroid excretion following conjugation by the liver. The response to stress by the adrenal cortex is very constant unless it has been exhausted by continued overstimulation due to trauma or in some cases due to lack of adrenal reserve following disease of the adrenals or severe malnutrition. We are indebted to Selye for the first detailed description of the stress reaction, which he divides into an early response or "stage of resistance" and the later response, "the stage of exhaustion and death." The adrenal corticoids responsible for these changes fall into three general categories. l The glucocorticoids consist mainly of hydrocortisone and cortisone. These hormones are probably responsible for gluconeogenesis resulting in conversion of tissue protein to sugar and liver glycogen, an increase in nitrogen excretion in the urine, a transient hyperglycemia and glycosuria and an eosinopenia, lymphopenia and polymorphonuclear leukocytosis. Cellular inflammatory changes as well as fibrosis are decreased. It is believed that these hormones act to protect
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cells against the injurious effects of the reaction to stress. The mineralocorticoids cause retention of sodium and increased excretion of potassium and include aldosterone and desoxycorticosterone acetate (DOCA). Whether or not the oliguria encountered after trauma is due chiefly to the mineralocorticoids or to posterior pituitary antidiuretic hormone is not yet clear. It may be that both factors are active. The third class of adrenal cortical hormones includes the 17-ketosteroids which are closely related to the sex hormones. It is understandable that increased urinary levels of the 17-ketosteroids can be demonstrated following injury; however, their precise role in the initial response to trauma is not entirely clear, except that they are associated with nitrogen retention and in general are anabolic with respect to protein, as contrasted to hydrocortisone which is catabolic. It would appear, then, that the response to injury results in peripheral vasoconstriction serving to counteract peripheral hemorrhage when present, causes increased cerebral blood flow, makes increased amounts of carbohydrate immediately available, results in the liberation of antibodies due to breakdown of lymphocytes and prepares the body to combat infection. ALTERATIONS IN METABOLISM FOLLOWING TRAUMA
The changes in metabolism which coincide with the alterations in endocrine function secondary to trauma must be understood to manage intelligently the injured patient in the immediate post-traumatic period. NEGATIVE NITROGEN BALANCE. The combined effects of starvation and increased tissue breakdown characteristically result in an increased urinary nitrogen excretion which may range from 12 grams of nitrogen to as high as 25 grams or more per day depending upon the severity of injury. The extent of nitrogen loss is related not only to the severity of trauma and extent of starvation but the state of nutrition of the patient prior to injury. The age of the patient is also a factor since elderly patients do not have the same response to trauma as is found in healthy, young adults. This catabolic phase typically lasts for five to seven days but may extend to several weeks if the injury is severe. 2 In an uncomplicated recovery, cessation of the catabolic phase coincides with an increased intake of protein and calories and a conversion to a positive nitrogen balance. This may last for a prolonged period depending on the food intake and extent of initial injury. There is some controversy as to whether it is desirable or even possible to overcome or diminish the negative nitrogen balance seen soon after trauma. This subject will be considered in more detail; however, it would appear that every effort should be made to increase the blood protein levels in the malnourished patient to prevent severe hypoproteinemia, wound dehiscence, infection, etc. in the postoperative period
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POTASSIUM. Increased loss of potassium in the urine is characteristic of the post-injury state and is apparently a combination of nitrogen breakdown, loss of electrolyte and water from body cells as well as inability of the kidney to conserve potassium. Patients on suction also lose potassium by this route. It appears that patients tolerate potassium loss for two or three days following injury without difficulty; however, after this time potassium stores must be replenished by the parenteral route. Potassium must be administered cautiously in the presence of an oliguria; with adequate urine output the patient usually will tolerate 6 to 9 grams of potassium chloride daily. A high carbon dioxide combining power suggests the possibility of a metabolic alkalosis associated with low potassium levels. This will generally respond to potassium administration. SODIUM, CHLORIDE AND WATER. There is usually a reduction in urinary excretion of sodium, chloride and water with retention of sodium predominating. It is not uncommon for these changes to be accompanied by a reduction in the serum sodium to 130 mEq. per liter. This paradoxical situation may be the result of water retention in the extracellular spaces as well as a shift of sodium into injured cells. It is felt that administration of physiological saline should be minimal in the early postoperative period. FAT METABOLISM. As may be predicted there is rapid oxidation of body fat immediately after injury. As the catabolic phase diminishes loss of body fat decreases and later in the anabolic period restoration of the body fat again occurs. BURNS
The physiologic changes seen after injury are so accentuated following a severe burn as to merit individual consideration. The immediate danger to the patient is the profound change in cardiovascular hemodynamics which may produce irreversible burn shock and if untreated usually appears within the first 48 to 72 hours after injury.3 Decreased blood volume results in hemoconcentration, decreased blood flow and anoxia of vital organs. The falling blood pressure and decreased cardiac output seriously affect the kidney, liver, brain and heart. A chain of events is set into motion which if uninterrupted is fatal. It is possible to consider the metabolic alterations following burns under the categories of local and systemic changes. LOCAL CHANGES. Injury of the capillaries in the burned area results in dilatation and increased permeability with escape of tissue fluid, proteins and electrolytes. Injury to the tissue cells in the burned area further contributes to these changes. As a result of increased capillary pressures due to vasodilatation and lowering of the effective oncotic pressure of the plasma, pronounced tissue edema occurs. 4
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In full thickness burns, thrombosis of the vessels removes red blood cells from the circulation. Extensive fluid loss is probably related to damage of the subcutaneous tissue in the region of the full thickness burn. Part of the edema fluid is reabsorbed by way of the lymphatic system. However, with increasing severity of tissue damage and lymphatic destruction as in severe full thickness burns, reabsorption is greatly delayed. The pathologic changes noted above form the basis of fluid therapy for the burned patient as there is a close relationship between the extent and depth of the burn and the quantity of fluid required to maintain the circulation. Analysis of the composition of edema fluid in burns has shown there may be as much as 4 grams of protein per 100 ml. in the fluid with a relative increase in the albumin fraction. In addition to the relatively large protein content of the edema fluid, it appears that there is an increase in the plasma protein which may be related to the more rapid loss of water and electrolytes from the vascular system. As previously noted, the increased capillary pressure and capillary permeability result in changes in water and electrolyte content. The loss of potassium from injured cells is effected by the adrenal cortex and is related to the increased sodium content of injured cells. Regardless of the exact mechanisms involved, the alterations in normal physiology indicate the need for prompt electrolyte and colloid replacement in the severely burned patient. SYSTEMIC CHANGES. Increased excretion of urinary nitrogen, protein loss in wound exudate and low protein intake are responsible for the negative nitrogen balance characteristic of severely burned patients. The amount of nitrogen loss in the urine is influenced by the depth and extent of the burn, state of nutrition prior to injury, and integrity of the adrenal cortex. The burned patient may excrete two or three times the normal 10 to 15 grams of urinary nitrogen per day, most of which appears as urea. The amount of nitrogen lost in wound exudates may reach 5 to 7 grams daily. There is evidence that nitrogen loss in malnourished patients is less extensive than that of the normal patient; however, these patients cannot tolerate the extent of trauma nor do they recover as rapidly as the well nourished patient. There is a rapid gain in total body water immediately after burning due to administration of fluids essential in treatment. This appears to be largely extracellular in nature. Water intoxication is a possible complication of overhydration and probably is a result of water shifts from extracellular fluid into the cells. This complication may be avoided by limiting oral intake of water and careful measurement of parenteral fluids. ANEMIA. The use of whole blood in the therapy of burns is controversial. Part of the difficulty arises from the fact that the hematocrit is usually high. Some investigators feel that the elevated hematocrit does
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not actually reflect the true situation relative to red cells because of a reduction in the blood volume. It appears that burn anemia is the result of local destruction of red blood cells, delayed hemolysis, thrombosis in capillaries of burned tissue, and sludging. Inasmuch as a burn anemia invariably appears five to seven days after a severe burn, it is felt by many that whole blood should be administered as part of the colloid therapy early following extensive burns. As fluid equilibrium is gradually restored, hematocrit and red blood cell determinations will help gauge the extent of red blood cell destruction. Pulse rate and blood pressure, while not as reliable as in hemorrhagic states, may indicate the need for increased protein and blood therapy. KIDNEY FuNCTION. The decrease in urinary output often encountered in the severely burned patient fortunately usually is the result of fluid loss with inadequate replacement rather than due to organic changes in the kidney. The oliguria encountered is the result of decreased plasma volume, diminished cardiac output and decreased blood pressure due to burn shock. This decrease in renal blood flow and fall in glomerular filtration rate causes renal ischemia and anoxia. Disturbance in tubular activity may result in loss of the kidney's ability to selectively excrete and reabsorb electrolytes and water. The loss of fixed base may lead to renal acidosis and fixed base depletion. Pathologically, there may be cloudy swelling in the tubular membranes as well as numerous casts. 5 In the presence of oliguria it becomes a matter of crucial importance to determine whether decreased urinary output is a sign of severe organic damage such as a lower nephron nephrosis or hemoglobinuric nephrosis or whether the decreased output is due to insufficient fluid replacement. Rapid administration of both plasma expanders and 5 per cent dextrose with careful measurement of the output and specific gravity may settle the matter. MISCELLANEOUS CHANGES. Osteoporosis and rapid muscle wasting are probably related to the length of immobilization, increased adrenal cortical activity and acute nitrogen loss. Infection is a very common and most serious complication contributing to the altered physiology of the burned patient. 3 Partial thickness burns may be converted to full thickness. The origin of infection in patients with full thickness burns appear to be bacteria which survive in the deeper layers in the skin. Natural body defenses are neutralized due to the destruction of the blood vessels and a natural culture media is present due to the dead tissue in the area. Outside contamination of the burn wound likewise may be a source of infection. Septicemia becomes manifest a few days after injury. Clinical signs include a gradual or rapid rise in temperature, which may reach very high levels, tachycardia, disorientation and paralytic ileus. Later manifestations include signs of hepatic and renal failure with hypotension.
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URINARY 17-0H CORTICOID OUTPUT IN SEVERE BURN P.G., 36-93-82 Age 6, N., 2;
BURN
i~40 'T ~ ()..c
t~ 30
i :
t
+
~~ :r ~ 20 ?E .... 10 .;
Debr i dement
Dressings changed
+
t
o~--------~~-----------------------
I
200~ Cortisone 100
8Hydrocortisone
!~~~~&~red Blood transfusions
Ht.40 NPN
#
42 4338 21 5.5 3.4 2.1
TP A G
C.F. iii iii iii iii
25 June
30 I
5
Lethargic
",,0 'v
~..orOo. Massive
'!;""V1r:?-~<9 ~
44 44 20 5.7 3.3 2.4
diarrhea ~
~ilirubi~uria 30 20 32
4.7
3.3 1.6 ++
+++
iii i " i 10 15
I
I
i
20
,/ u I Y
Fig. 1. Clinical course of 6 year old girl admitted following partial and full-thickness burns of 70 per cent of body surface. The patient expired on the 27th postburn day following continual spiking fever and evidence of hepatic failure.
Hepatic function in the early stages is usually quite adequate even in patients with extensive burns. However, the combined effects of the pyrexia, accelerated tissue breakdown and increased demands on the detoxifying mechanism commonly contribute to the onset of hepatic failure. The appearance of jaundice in the burned patient is frequently a sign of irreversible damage. In addition to these alterations in metabolism, adrenal insufficiency and exhaustion must be considered. The initial burn injury is a strong stimulus to increased adrenal corticoid output. There is ample evidence to indicate that patients with liver damage are unable to metabolize 17-hydroxicorticoids normally. Jaundiced patients have a smaller urinary
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excretion of urinary corticoids and there is some evidence that hepatic dysfunction depresses adrenal output. The following case history illustrates some of the severe derangements encountered in a severely burned patient. A 6 year old girl was brought to the hospital soon after sustaining severe burns. She had been playing with matches and her clothes caught fire. Examination revealed partial and full thickness burns involving the lower part of the face, all of the neck, upper extremities and lower extremities to the midcalf area. It was estimated that 70 per cent of the body surface was involved. On admission the pulse was 100 and respirations were 32 per minute. The clinical course is depicted in Figure 1. The patient had a febrile course which became accentuated approximately 5 days following initial injury. Urinary 17-hydroxycorticoid determinations were begun approximately 1 week after admission. The patient's urinary output ranged from 1400 to 2900 ml. daily. Because of her poor clinical condition and the low urinary corticoid levels despite the severe injury, hydrocortisone administration was begun. No improvement in the patient's clinical condition could be attributed to the steroid therapy. She continued to run a markedly febrile course and it was felt that the only hope of salvage was the application of homografts, therefore skin was taken from her father in preparation for grafting of the patient. Approximately 22 days after the burn the patient's condition began to deteriorate appreciably. Bile appeared in the urine, the patient became lethargic and a massive diarrhea appeared. The cephalin flocculation test at this time was 3+ in 24 hours. The patient expired on the twenty-seventh postburn day. At autopsy multiple abscesses were found in the myocardium, lungs and kidneys. Hemolytic enterococci were isolated postmortem from the blood and Staphylococcus aureus from the lungs. Despite the evidence of hepatic failure, the microscopic sections of the liver revealed only occasional chronic inflammatory cells in the portal spaces. The hepatic cells were not remarkable. The central veins were dilated and congested. Microscopic sections of the kidney revealed multiple abscesses in the medulla with some bacteria in the centers. The glomeruli showed capillary congestion. The tubules were not remarkable. Sections of the adrenal gland revealed congestion of the sinusoids. Lipid depletion of the cortical cells and diffuse hemorrhages in pericapsular areas were noted. The conclusion of the pathologists was that the patient died of extensive burns complicated by septicopyemia and multiple visceral abscesses. TRA UMA AND NUTRITION
It becomes apparent after considering the catabolic mechanisms set into effect following injury that careful attention must be paid to the nl}tritional aspects of treatment. This especially true in those patients who may have been malnourished prior to injury, patients with preexisting decrements such as liver disease, and especially the elderly patient. It appears that malnourished patients conserve nitrogen better than normal individuals probably because there is less readily available nitrpgen for excretion or a mild depletion of adrenal cortical reserve. It is ohj1racteristic, however, that should these patients encounter complications in their post-traumatic state their ability to withstand these
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added stresses is markedly diminished. Although plasma protein determinations are most useful in estimating protein needs, they are often maintained at near normal levels despite significant depletion of muscle and liver. This situation usually can be recognized by a history of poor food intake, weight loss and evidence of wasting of body fat and muscle. An intensive effort to increase protein and caloric intake is indicated to prevent a precipitous drop of plasma protein levels should the patient encounter some complication. If plasma levels drop suddenly there is loss of ability to maintain osmotic pressure and the patient may exhibit a shocklike state. In addition, lowered colloid osmotic pressure of the plasma permits water and electrolytes to accumulate outside the blood vessels. Should the plasma protein level fall to 5 grams with albumin at about 2.5 grams per 100 m!., edema becomes grossly demonstrable in dependent areas and may become generalized. During such periods the patient's body weight may actually increase, giving the mistaken impression of improved nutrition although the opposite is true. Other factors tending to increase edema are increased venous pressure which diminishes the amount of fluid returning to the circulation and accumulation of extracellular sodium. Adequate protein levels, especially of the globulin fractions, are necessary in the post-traumatic period in order to preserve the immunologic processes. The presence of infection and elevated temperatures may in themselves aggravate or cause hypoproteinemia by depressing protein synthesis, appetite and intake. If abscesses are formed and drained to the exterior, significant protein loss occurs as the fluid may contain 4 grams of protein per 100 m!. There is experimental evidence that spreading peritonitis causes loss of protein into the abdominal cavity and may result in a significant decrease in plasma proteins. The state of hepatic reserve is directly related to protein deficits following injury. Many of the protein fractions including fibrinogen, prothrombin and the globulins are produced by liver cells. Gamma globulin is produced by the reticuloendothelial system, part of which is in the liver. It is common to encounter a decrease in serum albumin prior to a reduction in total protein and this reversal may be an indication of impending hepatic insufficiency. Trauma involving the gastrointestinal tract may prolong the catabolic state. Oral intake is delayed resulting in difficulty in providing adequate protein. Intestinal fistulas result in direct loss of protein and interfere with absorption. Vomiting, if severe, causes dehydration and electrolyte imbalance earlier than hypoproteinemia, but may be an added factor. It is important to provide carbohydrate and fat as well as protein in the post-traumatic state. The protein-sparing effect of carbohydrate is well recognized and it appears that 100 grams of carbohydrate daily is sufficient to prevent formation of acetone bodies which may deplete alkaline reserves and result in acidosis.
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There is controversy as to whether the negative nitrogen balance following injury is a necessary state which must be accepted or whether every effort should be made to provide high protein intake in an effort to diminish or completely compensate for the loss of protein. It is our feeling that every effort should be made to provide adequate protein intake early in the postoperative period, especially with elderly or malnourished patients. The use of plasma proteins and whole blood from a nutritional aspect alone deserves some comment. It has been shown by Allen and associates that puppies will achieve normal growth rates with only dog plasma administered. In general, it is felt that while plasma is of great value in helping to restore plasma protein levels, it is too expensive and conversion to other proteins too inefficient to recommend for nutritional purposes only. Whole blood likewise should be reserved for patients with decreased hemoglobulin levels inasmuch as in the presence of anemia the hemopoietic system has first call on available protein stores. The various protein hydrolysates are valuable in correcting post-traumatic hypoproteinemia as they provide readily available protein together with suitable quantities of carbohydrate. A most valuable addition to therapy for post-traumatic malnutrition has been intravenous fat emulsion. 7 Numerous studies demonstrate that intravenous fat is metabolized efficiently and has a powerful proteinsparing effect. Early attempts to utilize intravenous fats were accompanied by a high incidence of side reactions. At the present time the reported incidence of minor febrile reaction varies from 2 to 30 per cent depending upon the closeness with which the temperature is followed. These minor temperature elevations are probably related to increased metabolic heat or pyrogenic reactions. Transient elevations of bromsulphalein retention following infusions of fat as well as minor elevations of the thymol turbidity and cephalin flocculation tests have been reported. The liver function tests returned to normal after completion of the series of infusions. Autopsies have failed to show significant lesions in patients receiving fat emulsions. The only significant toxic reaction related to intravenous feeding is a bleeding tendency and this usually is seen only in patients receiving 15 or more units. It is characterized by fever, lethargy, epistaxis, petechiae, gastrointestinal bleeding, hepatosplenomegly, etc. There is some indication that symptoms may subside following the administration of hydrocortisone. There have been very few cases of this type reported. At the present time it is probably advisable to limit the number of infusions in any six month period to 14. Nutritional Problems in Severe Burns
The severely burned patient presents a problem in nutrition which taxns the most experienced physician. The combination of factors leading
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to protein depletion is most difficult to handle. There is persistent protein loss through the burn wound, which can only be corrected by coverage with split skin grafts. Infection is commonly present and acts to increase the negative nitrogen balance by depressing conversion of amino acids to tissue protein. The presence of high temperatures tend to slow the repairing process and augment tissue breakdown. If a burn anemia is present, this must be corrected in order that available nitrogen is not diverted to hemoglobin formation. The problem of achieving high protein intake levels is complicated by anorexia due to pain, wound drainage and fever. It has been our experience that chronic burned patients require daily intake levels near 5000 calories and 175 to 200 grams of proteins. These quantities are difficult to approach and require a judicious combination of oral intake including high calorie, high protein tube feedings with supplementation by parenteral administration of amino acids, plasma, whole blood and intravenous fat. Corticotropin (ACTH) may be most helpful in achieving a higher food intake in selected patients, although not all patients respond to ACTH. Those who respond experience an increased feeling of well-being with improvement in appetite. In addition the drug may act to suppress fever, toxicity and malaise. Some of the weight gain experienced by these patients is due to water retention but in the presence of improved appetite the increased intake may result in elevation of blood proteins and a positive nitrogen balance. TRAUMA AND WOUND HEALING
The delay in wound healing often encountered after severe injury is directly related to the extent of local tissue damage and prolongation of the time required for phagocytosis and repair. In severe wounds there is a greater quantity of serum, blood and tissue elements which must be removed by enzymatic action, absorption and phagocytosis, and if the blood supply to the area is compromised there is a lag phase with a delay in the appearance of new cellular elements of the blood, wandering tissue cells and capillaries which make up the granulation tissue necessary for healing. 7 Other local factors which affect wound healing are related to the site of the injury and the type of tissue involved, that is, skin, muscle, parenchymatous organs, etc., as well as relationship to joints and extent of movement of the injured tissues. There is a direct relationship between the degree of contamination of wounds and rapidity of wound healing. Bacterial proliferation results in additional exudation, tissue necrosis and prolongation of the lag phase of wound healing which precedes the reparative processes. The nature of the trauma is likewise of considerable importance. High velocity missiles are much more serious due to widespread tissue
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damage resulting from the shock wave as well as direct injury. Damaged tissues with a decreased blood supply must rely upon the lymphatic system for removal of waste substances and an influx of granulation tissue elements. The nature of the tissue is of prime importance with respect to ability to regenerate. In general the more highly specialized the tissue the less readily does it recover from injury. An example is repair in peripheral nerves following injury. The reaction of Wallerian degeneration which occurs following nerve injury includes degeneration ofaxons and myelin sheath in the proximal stump near the point of injury, degeneration of axons and myelin sheath throughout the distal nerve trunk, infiltration of macrophages into nerve fibers and Schwann cells and fibrous replacement of the areas which are not occupied by regenerating nerve tissue. There is still considerable controversy over the advisability of primary repair following an acute peripheral nerve injury due to a gunshot wound because of the difficulty in delineating the longitudinal extent of injury. The primary repair of muscle tissue is quite difficult due to its friability and healing is largely by connective tissue fibrosis. The difficulty in obtaining satisfactory healing following tendon injury is well known and related to the acellularity of the tissue, excessive scar formation and frequent impairment of the blood supply. Injuries due to thermal, chemical and electrical energy present additional complications usually related to the extent of tissue damage. The best example is seen in electrical injuries. These are complicated by extensive damage at the points of greatest resistance, destruction of the vascular supply and injury to skin, nerves, tendons, muscle and bones. The systemic factors directly related to wound healing following trauma are associated injuries, presence of chronic illness, status of the circulatory system and the nutritional state of the patient. Delay in primary wound healing may be anticipated in patients with extensive multiple injuries, those with chronic debilitating disease and in the elderly patient. Malnutrition with or without anemia, however, is probably one of the most important factors relating to wound healing. As noted in the foregoing section, the response to injury is characterized by a catabolic phase with increased protein loss and delay of protein synthesis. Chronic protein depletion results in delay in epithelization, proliferation of connective tissue and attainment of wound strength. There is also evidence that the immunologic response is depressed with a resultant increase in susceptibility to infection. The increased secretion of hormones following trauma also affect the inflammatory reaction and rate of wound healing. The mechanism of these effects is not completely understood but apparently is related to a decrease in protein synthesis and the possible depression of cell growth. Vitamin C deficiency results in a disappearance of collagen, failure of maturity of fibroblasts and defective capillaries.
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SUMMARY
The physiological response to injury is characterized by an increased secretion of adrenal cortical hormones. The adrenal corticoids are responsible for gluconeogenesis resulting in conversion of tissue protein to sugar and liver glycogen, an increase in nitrogen excretion in the urine, hyperglycemia, glycosuria and an eosinopenia, lymphopenia and polymorphonuclear leukocytosis. In addition, there is a retention of sodium, chloride and water and ariincreased excretion of potassium. The above changes are part of the stress reaction. The physiologic changes seen after a severe burn are similar, but greatly accentuated. The immediate danger to the patient is that of irreversible burn shock. Injury of the capillaries and cells due to burns results in escape of tissue fluid, proteins and electrolytes. Systemic changes following burns include a negative nitrogen balance, anemia, oliguria and infection, the last of which is a common and serious complication. Careful attention to the nutritional aspects of treatment following injury is required, especially if the period of no food intake is prolonged. Factors that may complicate the return to a positive nitrogen balance include infection and abscesses, depressed hepatic reserve, trauma involving the gastrointestinal tract, intestinal fistulas, etc. A valuable recent addition to the therapy for post-traumatic malnutrition is intravenous fat emulsion. The delay in wound healing often encountered after injury is related to a combination of local factors including extent and location of injury, type of tissue, blood supply, degree of contamination, and systemic factors including the presence of associated injuries, pre-existing illness, age, nutrition, and the extent of the metabolic response to trauma. REFERENCES 1. Allen, J. G., Harkins, H. N., Moyer, C. A. and Rhoads, J. E.: Surgery, Principles and Practice. Philadelphia, J. B. Lippincott Co., 1957. 2. Artz, C. P. and Hardy, J.: Complications in Surgery and Their Management. Philadelphia, W. B. Saunders Co., 1960. 3. Artz, C. T. and Reiss, E.: The Treatment of Burns. Philadelphia, W. B. Saunders Co., 1957. 4. Bowers, W. F.: Surgery of Trauma. Philadelphia, J. B. Lippincott Co., 1953. 5. Cope, 0., Graham, J. B., Moore, F. D. and Ball, M. R.: The Nature of the Shift of Plasma Protein to the Extravascular Space Following Thermal Trauma. Ann. Surg. 128: 1041-1055, 1948. 6. Marshall, W. H.: Clinical Use of Intravenous Fat in Surgical Patients. Tr. West. Surgical A. 66: 181-185, 1958. 7. Zimmerman, L. M. and Levine, R. : Physiologic Principles of Surgery. Philadelphia, W. B. Saunders Co., 1957.
1853 West Polk Street .Chicago 12, Illinois
JOHN H. SCHNEEWIND, M.D., F.A.C.S. Associate Professor of Surgery, University of Illinois College of Medicine; Chief of Emergency Service, Research and Educational Hospitals; Assistant AUending Surgeon, Presbyterian-St. Luke's Hospital; Associate Surgeon, Cook County Hospital
PHYSIOLOGICAL RESPONSE TO INJURY AN UNDERSTANDING of the complicated response of the body to stress, fear or actual organic injury is required for the proper management of the acutely injured patient. These changes are regulated chiefly by the endocrine system mediated through the autonomic nervous system. It appears that stress or injury stimulates increased secretion of epinephrine from the adrenal medulla into the blood stream with activation of the anterior pituitary and liberation of adrenal corticotropic hormone. The result is an immediate increase in output of hormones of the adrenal cortex. These rapid increases have been documented by studies of blood levels of steroids immediately following trauma as well as measurement of the urinary steroid excretion following conjugation by the liver. The response to stress by the adrenal cortex is very constant unless it has been exhausted by continued overstimulation due to trauma or in some cases due to lack of adrenal reserve following disease of the adrenals or severe malnutrition. We are indebted to Selye for the first detailed description of the stress reaction, which he divides into an early response or "stage of resistance" and the later response, "the stage of exhaustion and death." The adrenal corticoids responsible for these changes fall into three general categories. l The glucocorticoids consist mainly of hydrocortisone and cortisone. These hormones are probably responsible for gluconeogenesis resulting in conversion of tissue protein to sugar and liver glycogen, an increase in nitrogen excretion in the urine, a transient hyperglycemia and glycosuria and an eosinopenia, lymphopenia and polymorphonuclear leukocytosis. Cellular inflammatory changes as well as fibrosis are decreased. It is believed that these hormones act to protect
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cells against the injurious effects of the reaction to stress. The mineralocorticoids cause retention of sodium and increased excretion of potassium and include aldosterone and desoxycorticosterone acetate (DOCA). Whether or not the oliguria encountered after trauma is due chiefly to the mineralocorticoids or to posterior pituitary antidiuretic hormone is not yet clear. It may be that both factors are active. The third class of adrenal cortical hormones includes the 17-ketosteroids which are closely related to the sex hormones. It is understandable that increased urinary levels of the 17-ketosteroids can be demonstrated following injury; however, their precise role in the initial response to trauma is not entirely clear, except that they are associated with nitrogen retention and in general are anabolic with respect to protein, as contrasted to hydrocortisone which is catabolic. It would appear, then, that the response to injury results in peripheral vasoconstriction serving to counteract peripheral hemorrhage when present, causes increased cerebral blood flow, makes increased amounts of carbohydrate immediately available, results in the liberation of antibodies due to breakdown of lymphocytes and prepares the body to combat infection. ALTERATIONS IN METABOLISM FOLLOWING TRAUMA
The changes in metabolism which coincide with the alterations in endocrine function secondary to trauma must be understood to manage intelligently the injured patient in the immediate post-traumatic period. NEGATIVE NITROGEN BALANCE. The combined effects of starvation and increased tissue breakdown characteristically result in an increased urinary nitrogen excretion which may range from 12 grams of nitrogen to as high as 25 grams or more per day depending upon the severity of injury. The extent of nitrogen loss is related not only to the severity of trauma and extent of starvation but the state of nutrition of the patient prior to injury. The age of the patient is also a factor since elderly patients do not have the same response to trauma as is found in healthy, young adults. This catabolic phase typically lasts for five to seven days but may extend to several weeks if the injury is severe. 2 In an uncomplicated recovery, cessation of the catabolic phase coincides with an increased intake of protein and calories and a conversion to a positive nitrogen balance. This may last for a prolonged period depending on the food intake and extent of initial injury. There is some controversy as to whether it is desirable or even possible to overcome or diminish the negative nitrogen balance seen soon after trauma. This subject will be considered in more detail; however, it would appear that every effort should be made to increase the blood protein levels in the malnourished patient to prevent severe hypoproteinemia, wound dehiscence, infection, etc. in the postoperative period
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POTASSIUM. Increased loss of potassium in the urine is characteristic of the post-injury state and is apparently a combination of nitrogen breakdown, loss of electrolyte and water from body cells as well as inability of the kidney to conserve potassium. Patients on suction also lose potassium by this route. It appears that patients tolerate potassium loss for two or three days following injury without difficulty; however, after this time potassium stores must be replenished by the parenteral route. Potassium must be administered cautiously in the presence of an oliguria; with adequate urine output the patient usually will tolerate 6 to 9 grams of potassium chloride daily. A high carbon dioxide combining power suggests the possibility of a metabolic alkalosis associated with low potassium levels. This will generally respond to potassium administration. SODIUM, CHLORIDE AND WATER. There is usually a reduction in urinary excretion of sodium, chloride and water with retention of sodium predominating. It is not uncommon for these changes to be accompanied by a reduction in the serum sodium to 130 mEq. per liter. This paradoxical situation may be the result of water retention in the extracellular spaces as well as a shift of sodium into injured cells. It is felt that administration of physiological saline should be minimal in the early postoperative period. FAT METABOLISM. As may be predicted there is rapid oxidation of body fat immediately after injury. As the catabolic phase diminishes loss of body fat decreases and later in the anabolic period restoration of the body fat again occurs. BURNS
The physiologic changes seen after injury are so accentuated following a severe burn as to merit individual consideration. The immediate danger to the patient is the profound change in cardiovascular hemodynamics which may produce irreversible burn shock and if untreated usually appears within the first 48 to 72 hours after injury.3 Decreased blood volume results in hemoconcentration, decreased blood flow and anoxia of vital organs. The falling blood pressure and decreased cardiac output seriously affect the kidney, liver, brain and heart. A chain of events is set into motion which if uninterrupted is fatal. It is possible to consider the metabolic alterations following burns under the categories of local and systemic changes. LOCAL CHANGES. Injury of the capillaries in the burned area results in dilatation and increased permeability with escape of tissue fluid, proteins and electrolytes. Injury to the tissue cells in the burned area further contributes to these changes. As a result of increased capillary pressures due to vasodilatation and lowering of the effective oncotic pressure of the plasma, pronounced tissue edema occurs. 4
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In full thickness burns, thrombosis of the vessels removes red blood cells from the circulation. Extensive fluid loss is probably related to damage of the subcutaneous tissue in the region of the full thickness burn. Part of the edema fluid is reabsorbed by way of the lymphatic system. However, with increasing severity of tissue damage and lymphatic destruction as in severe full thickness burns, reabsorption is greatly delayed. The pathologic changes noted above form the basis of fluid therapy for the burned patient as there is a close relationship between the extent and depth of the burn and the quantity of fluid required to maintain the circulation. Analysis of the composition of edema fluid in burns has shown there may be as much as 4 grams of protein per 100 ml. in the fluid with a relative increase in the albumin fraction. In addition to the relatively large protein content of the edema fluid, it appears that there is an increase in the plasma protein which may be related to the more rapid loss of water and electrolytes from the vascular system. As previously noted, the increased capillary pressure and capillary permeability result in changes in water and electrolyte content. The loss of potassium from injured cells is effected by the adrenal cortex and is related to the increased sodium content of injured cells. Regardless of the exact mechanisms involved, the alterations in normal physiology indicate the need for prompt electrolyte and colloid replacement in the severely burned patient. SYSTEMIC CHANGES. Increased excretion of urinary nitrogen, protein loss in wound exudate and low protein intake are responsible for the negative nitrogen balance characteristic of severely burned patients. The amount of nitrogen loss in the urine is influenced by the depth and extent of the burn, state of nutrition prior to injury, and integrity of the adrenal cortex. The burned patient may excrete two or three times the normal 10 to 15 grams of urinary nitrogen per day, most of which appears as urea. The amount of nitrogen lost in wound exudates may reach 5 to 7 grams daily. There is evidence that nitrogen loss in malnourished patients is less extensive than that of the normal patient; however, these patients cannot tolerate the extent of trauma nor do they recover as rapidly as the well nourished patient. There is a rapid gain in total body water immediately after burning due to administration of fluids essential in treatment. This appears to be largely extracellular in nature. Water intoxication is a possible complication of overhydration and probably is a result of water shifts from extracellular fluid into the cells. This complication may be avoided by limiting oral intake of water and careful measurement of parenteral fluids. ANEMIA. The use of whole blood in the therapy of burns is controversial. Part of the difficulty arises from the fact that the hematocrit is usually high. Some investigators feel that the elevated hematocrit does
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not actually reflect the true situation relative to red cells because of a reduction in the blood volume. It appears that burn anemia is the result of local destruction of red blood cells, delayed hemolysis, thrombosis in capillaries of burned tissue, and sludging. Inasmuch as a burn anemia invariably appears five to seven days after a severe burn, it is felt by many that whole blood should be administered as part of the colloid therapy early following extensive burns. As fluid equilibrium is gradually restored, hematocrit and red blood cell determinations will help gauge the extent of red blood cell destruction. Pulse rate and blood pressure, while not as reliable as in hemorrhagic states, may indicate the need for increased protein and blood therapy. KIDNEY FuNCTION. The decrease in urinary output often encountered in the severely burned patient fortunately usually is the result of fluid loss with inadequate replacement rather than due to organic changes in the kidney. The oliguria encountered is the result of decreased plasma volume, diminished cardiac output and decreased blood pressure due to burn shock. This decrease in renal blood flow and fall in glomerular filtration rate causes renal ischemia and anoxia. Disturbance in tubular activity may result in loss of the kidney's ability to selectively excrete and reabsorb electrolytes and water. The loss of fixed base may lead to renal acidosis and fixed base depletion. Pathologically, there may be cloudy swelling in the tubular membranes as well as numerous casts. 5 In the presence of oliguria it becomes a matter of crucial importance to determine whether decreased urinary output is a sign of severe organic damage such as a lower nephron nephrosis or hemoglobinuric nephrosis or whether the decreased output is due to insufficient fluid replacement. Rapid administration of both plasma expanders and 5 per cent dextrose with careful measurement of the output and specific gravity may settle the matter. MISCELLANEOUS CHANGES. Osteoporosis and rapid muscle wasting are probably related to the length of immobilization, increased adrenal cortical activity and acute nitrogen loss. Infection is a very common and most serious complication contributing to the altered physiology of the burned patient. 3 Partial thickness burns may be converted to full thickness. The origin of infection in patients with full thickness burns appear to be bacteria which survive in the deeper layers in the skin. Natural body defenses are neutralized due to the destruction of the blood vessels and a natural culture media is present due to the dead tissue in the area. Outside contamination of the burn wound likewise may be a source of infection. Septicemia becomes manifest a few days after injury. Clinical signs include a gradual or rapid rise in temperature, which may reach very high levels, tachycardia, disorientation and paralytic ileus. Later manifestations include signs of hepatic and renal failure with hypotension.
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URINARY 17-0H CORTICOID OUTPUT IN SEVERE BURN P.G., 36-93-82 Age 6, N., 2;
BURN
i~40 'T ~ ()..c
t~ 30
i :
t
+
~~ :r ~ 20 ?E .... 10 .;
Debr i dement
Dressings changed
+
t
o~--------~~-----------------------
I
200~ Cortisone 100
8Hydrocortisone
!~~~~&~red Blood transfusions
Ht.40 NPN
#
42 4338 21 5.5 3.4 2.1
TP A G
C.F. iii iii iii iii
25 June
30 I
5
Lethargic
",,0 'v
~..orOo. Massive
'!;""V1r:?-~<9 ~
44 44 20 5.7 3.3 2.4
diarrhea ~
~ilirubi~uria 30 20 32
4.7
3.3 1.6 ++
+++
iii i " i 10 15
I
I
i
20
,/ u I Y
Fig. 1. Clinical course of 6 year old girl admitted following partial and full-thickness burns of 70 per cent of body surface. The patient expired on the 27th postburn day following continual spiking fever and evidence of hepatic failure.
Hepatic function in the early stages is usually quite adequate even in patients with extensive burns. However, the combined effects of the pyrexia, accelerated tissue breakdown and increased demands on the detoxifying mechanism commonly contribute to the onset of hepatic failure. The appearance of jaundice in the burned patient is frequently a sign of irreversible damage. In addition to these alterations in metabolism, adrenal insufficiency and exhaustion must be considered. The initial burn injury is a strong stimulus to increased adrenal corticoid output. There is ample evidence to indicate that patients with liver damage are unable to metabolize 17-hydroxicorticoids normally. Jaundiced patients have a smaller urinary
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excretion of urinary corticoids and there is some evidence that hepatic dysfunction depresses adrenal output. The following case history illustrates some of the severe derangements encountered in a severely burned patient. A 6 year old girl was brought to the hospital soon after sustaining severe burns. She had been playing with matches and her clothes caught fire. Examination revealed partial and full thickness burns involving the lower part of the face, all of the neck, upper extremities and lower extremities to the midcalf area. It was estimated that 70 per cent of the body surface was involved. On admission the pulse was 100 and respirations were 32 per minute. The clinical course is depicted in Figure 1. The patient had a febrile course which became accentuated approximately 5 days following initial injury. Urinary 17-hydroxycorticoid determinations were begun approximately 1 week after admission. The patient's urinary output ranged from 1400 to 2900 ml. daily. Because of her poor clinical condition and the low urinary corticoid levels despite the severe injury, hydrocortisone administration was begun. No improvement in the patient's clinical condition could be attributed to the steroid therapy. She continued to run a markedly febrile course and it was felt that the only hope of salvage was the application of homografts, therefore skin was taken from her father in preparation for grafting of the patient. Approximately 22 days after the burn the patient's condition began to deteriorate appreciably. Bile appeared in the urine, the patient became lethargic and a massive diarrhea appeared. The cephalin flocculation test at this time was 3+ in 24 hours. The patient expired on the twenty-seventh postburn day. At autopsy multiple abscesses were found in the myocardium, lungs and kidneys. Hemolytic enterococci were isolated postmortem from the blood and Staphylococcus aureus from the lungs. Despite the evidence of hepatic failure, the microscopic sections of the liver revealed only occasional chronic inflammatory cells in the portal spaces. The hepatic cells were not remarkable. The central veins were dilated and congested. Microscopic sections of the kidney revealed multiple abscesses in the medulla with some bacteria in the centers. The glomeruli showed capillary congestion. The tubules were not remarkable. Sections of the adrenal gland revealed congestion of the sinusoids. Lipid depletion of the cortical cells and diffuse hemorrhages in pericapsular areas were noted. The conclusion of the pathologists was that the patient died of extensive burns complicated by septicopyemia and multiple visceral abscesses. TRA UMA AND NUTRITION
It becomes apparent after considering the catabolic mechanisms set into effect following injury that careful attention must be paid to the nl}tritional aspects of treatment. This especially true in those patients who may have been malnourished prior to injury, patients with preexisting decrements such as liver disease, and especially the elderly patient. It appears that malnourished patients conserve nitrogen better than normal individuals probably because there is less readily available nitrpgen for excretion or a mild depletion of adrenal cortical reserve. It is ohj1racteristic, however, that should these patients encounter complications in their post-traumatic state their ability to withstand these
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added stresses is markedly diminished. Although plasma protein determinations are most useful in estimating protein needs, they are often maintained at near normal levels despite significant depletion of muscle and liver. This situation usually can be recognized by a history of poor food intake, weight loss and evidence of wasting of body fat and muscle. An intensive effort to increase protein and caloric intake is indicated to prevent a precipitous drop of plasma protein levels should the patient encounter some complication. If plasma levels drop suddenly there is loss of ability to maintain osmotic pressure and the patient may exhibit a shocklike state. In addition, lowered colloid osmotic pressure of the plasma permits water and electrolytes to accumulate outside the blood vessels. Should the plasma protein level fall to 5 grams with albumin at about 2.5 grams per 100 m!., edema becomes grossly demonstrable in dependent areas and may become generalized. During such periods the patient's body weight may actually increase, giving the mistaken impression of improved nutrition although the opposite is true. Other factors tending to increase edema are increased venous pressure which diminishes the amount of fluid returning to the circulation and accumulation of extracellular sodium. Adequate protein levels, especially of the globulin fractions, are necessary in the post-traumatic period in order to preserve the immunologic processes. The presence of infection and elevated temperatures may in themselves aggravate or cause hypoproteinemia by depressing protein synthesis, appetite and intake. If abscesses are formed and drained to the exterior, significant protein loss occurs as the fluid may contain 4 grams of protein per 100 m!. There is experimental evidence that spreading peritonitis causes loss of protein into the abdominal cavity and may result in a significant decrease in plasma proteins. The state of hepatic reserve is directly related to protein deficits following injury. Many of the protein fractions including fibrinogen, prothrombin and the globulins are produced by liver cells. Gamma globulin is produced by the reticuloendothelial system, part of which is in the liver. It is common to encounter a decrease in serum albumin prior to a reduction in total protein and this reversal may be an indication of impending hepatic insufficiency. Trauma involving the gastrointestinal tract may prolong the catabolic state. Oral intake is delayed resulting in difficulty in providing adequate protein. Intestinal fistulas result in direct loss of protein and interfere with absorption. Vomiting, if severe, causes dehydration and electrolyte imbalance earlier than hypoproteinemia, but may be an added factor. It is important to provide carbohydrate and fat as well as protein in the post-traumatic state. The protein-sparing effect of carbohydrate is well recognized and it appears that 100 grams of carbohydrate daily is sufficient to prevent formation of acetone bodies which may deplete alkaline reserves and result in acidosis.
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There is controversy as to whether the negative nitrogen balance following injury is a necessary state which must be accepted or whether every effort should be made to provide high protein intake in an effort to diminish or completely compensate for the loss of protein. It is our feeling that every effort should be made to provide adequate protein intake early in the postoperative period, especially with elderly or malnourished patients. The use of plasma proteins and whole blood from a nutritional aspect alone deserves some comment. It has been shown by Allen and associates that puppies will achieve normal growth rates with only dog plasma administered. In general, it is felt that while plasma is of great value in helping to restore plasma protein levels, it is too expensive and conversion to other proteins too inefficient to recommend for nutritional purposes only. Whole blood likewise should be reserved for patients with decreased hemoglobulin levels inasmuch as in the presence of anemia the hemopoietic system has first call on available protein stores. The various protein hydrolysates are valuable in correcting post-traumatic hypoproteinemia as they provide readily available protein together with suitable quantities of carbohydrate. A most valuable addition to therapy for post-traumatic malnutrition has been intravenous fat emulsion. 7 Numerous studies demonstrate that intravenous fat is metabolized efficiently and has a powerful proteinsparing effect. Early attempts to utilize intravenous fats were accompanied by a high incidence of side reactions. At the present time the reported incidence of minor febrile reaction varies from 2 to 30 per cent depending upon the closeness with which the temperature is followed. These minor temperature elevations are probably related to increased metabolic heat or pyrogenic reactions. Transient elevations of bromsulphalein retention following infusions of fat as well as minor elevations of the thymol turbidity and cephalin flocculation tests have been reported. The liver function tests returned to normal after completion of the series of infusions. Autopsies have failed to show significant lesions in patients receiving fat emulsions. The only significant toxic reaction related to intravenous feeding is a bleeding tendency and this usually is seen only in patients receiving 15 or more units. It is characterized by fever, lethargy, epistaxis, petechiae, gastrointestinal bleeding, hepatosplenomegly, etc. There is some indication that symptoms may subside following the administration of hydrocortisone. There have been very few cases of this type reported. At the present time it is probably advisable to limit the number of infusions in any six month period to 14. Nutritional Problems in Severe Burns
The severely burned patient presents a problem in nutrition which taxns the most experienced physician. The combination of factors leading
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to protein depletion is most difficult to handle. There is persistent protein loss through the burn wound, which can only be corrected by coverage with split skin grafts. Infection is commonly present and acts to increase the negative nitrogen balance by depressing conversion of amino acids to tissue protein. The presence of high temperatures tend to slow the repairing process and augment tissue breakdown. If a burn anemia is present, this must be corrected in order that available nitrogen is not diverted to hemoglobin formation. The problem of achieving high protein intake levels is complicated by anorexia due to pain, wound drainage and fever. It has been our experience that chronic burned patients require daily intake levels near 5000 calories and 175 to 200 grams of proteins. These quantities are difficult to approach and require a judicious combination of oral intake including high calorie, high protein tube feedings with supplementation by parenteral administration of amino acids, plasma, whole blood and intravenous fat. Corticotropin (ACTH) may be most helpful in achieving a higher food intake in selected patients, although not all patients respond to ACTH. Those who respond experience an increased feeling of well-being with improvement in appetite. In addition the drug may act to suppress fever, toxicity and malaise. Some of the weight gain experienced by these patients is due to water retention but in the presence of improved appetite the increased intake may result in elevation of blood proteins and a positive nitrogen balance. TRAUMA AND WOUND HEALING
The delay in wound healing often encountered after severe injury is directly related to the extent of local tissue damage and prolongation of the time required for phagocytosis and repair. In severe wounds there is a greater quantity of serum, blood and tissue elements which must be removed by enzymatic action, absorption and phagocytosis, and if the blood supply to the area is compromised there is a lag phase with a delay in the appearance of new cellular elements of the blood, wandering tissue cells and capillaries which make up the granulation tissue necessary for healing. 7 Other local factors which affect wound healing are related to the site of the injury and the type of tissue involved, that is, skin, muscle, parenchymatous organs, etc., as well as relationship to joints and extent of movement of the injured tissues. There is a direct relationship between the degree of contamination of wounds and rapidity of wound healing. Bacterial proliferation results in additional exudation, tissue necrosis and prolongation of the lag phase of wound healing which precedes the reparative processes. The nature of the trauma is likewise of considerable importance. High velocity missiles are much more serious due to widespread tissue
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damage resulting from the shock wave as well as direct injury. Damaged tissues with a decreased blood supply must rely upon the lymphatic system for removal of waste substances and an influx of granulation tissue elements. The nature of the tissue is of prime importance with respect to ability to regenerate. In general the more highly specialized the tissue the less readily does it recover from injury. An example is repair in peripheral nerves following injury. The reaction of Wallerian degeneration which occurs following nerve injury includes degeneration ofaxons and myelin sheath in the proximal stump near the point of injury, degeneration of axons and myelin sheath throughout the distal nerve trunk, infiltration of macrophages into nerve fibers and Schwann cells and fibrous replacement of the areas which are not occupied by regenerating nerve tissue. There is still considerable controversy over the advisability of primary repair following an acute peripheral nerve injury due to a gunshot wound because of the difficulty in delineating the longitudinal extent of injury. The primary repair of muscle tissue is quite difficult due to its friability and healing is largely by connective tissue fibrosis. The difficulty in obtaining satisfactory healing following tendon injury is well known and related to the acellularity of the tissue, excessive scar formation and frequent impairment of the blood supply. Injuries due to thermal, chemical and electrical energy present additional complications usually related to the extent of tissue damage. The best example is seen in electrical injuries. These are complicated by extensive damage at the points of greatest resistance, destruction of the vascular supply and injury to skin, nerves, tendons, muscle and bones. The systemic factors directly related to wound healing following trauma are associated injuries, presence of chronic illness, status of the circulatory system and the nutritional state of the patient. Delay in primary wound healing may be anticipated in patients with extensive multiple injuries, those with chronic debilitating disease and in the elderly patient. Malnutrition with or without anemia, however, is probably one of the most important factors relating to wound healing. As noted in the foregoing section, the response to injury is characterized by a catabolic phase with increased protein loss and delay of protein synthesis. Chronic protein depletion results in delay in epithelization, proliferation of connective tissue and attainment of wound strength. There is also evidence that the immunologic response is depressed with a resultant increase in susceptibility to infection. The increased secretion of hormones following trauma also affect the inflammatory reaction and rate of wound healing. The mechanism of these effects is not completely understood but apparently is related to a decrease in protein synthesis and the possible depression of cell growth. Vitamin C deficiency results in a disappearance of collagen, failure of maturity of fibroblasts and defective capillaries.
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SUMMARY
The physiological response to injury is characterized by an increased secretion of adrenal cortical hormones. The adrenal corticoids are responsible for gluconeogenesis resulting in conversion of tissue protein to sugar and liver glycogen, an increase in nitrogen excretion in the urine, hyperglycemia, glycosuria and an eosinopenia, lymphopenia and polymorphonuclear leukocytosis. In addition, there is a retention of sodium, chloride and water and ariincreased excretion of potassium. The above changes are part of the stress reaction. The physiologic changes seen after a severe burn are similar, but greatly accentuated. The immediate danger to the patient is that of irreversible burn shock. Injury of the capillaries and cells due to burns results in escape of tissue fluid, proteins and electrolytes. Systemic changes following burns include a negative nitrogen balance, anemia, oliguria and infection, the last of which is a common and serious complication. Careful attention to the nutritional aspects of treatment following injury is required, especially if the period of no food intake is prolonged. Factors that may complicate the return to a positive nitrogen balance include infection and abscesses, depressed hepatic reserve, trauma involving the gastrointestinal tract, intestinal fistulas, etc. A valuable recent addition to the therapy for post-traumatic malnutrition is intravenous fat emulsion. The delay in wound healing often encountered after injury is related to a combination of local factors including extent and location of injury, type of tissue, blood supply, degree of contamination, and systemic factors including the presence of associated injuries, pre-existing illness, age, nutrition, and the extent of the metabolic response to trauma. REFERENCES 1. Allen, J. G., Harkins, H. N., Moyer, C. A. and Rhoads, J. E.: Surgery, Principles and Practice. Philadelphia, J. B. Lippincott Co., 1957. 2. Artz, C. P. and Hardy, J.: Complications in Surgery and Their Management. Philadelphia, W. B. Saunders Co., 1960. 3. Artz, C. T. and Reiss, E.: The Treatment of Burns. Philadelphia, W. B. Saunders Co., 1957. 4. Bowers, W. F.: Surgery of Trauma. Philadelphia, J. B. Lippincott Co., 1953. 5. Cope, 0., Graham, J. B., Moore, F. D. and Ball, M. R.: The Nature of the Shift of Plasma Protein to the Extravascular Space Following Thermal Trauma. Ann. Surg. 128: 1041-1055, 1948. 6. Marshall, W. H.: Clinical Use of Intravenous Fat in Surgical Patients. Tr. West. Surgical A. 66: 181-185, 1958. 7. Zimmerman, L. M. and Levine, R. : Physiologic Principles of Surgery. Philadelphia, W. B. Saunders Co., 1957.
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