tissue fuel and weight loss after injury'mortality was 3.5%. between the lackofconcern with...

J. clin. Path., 23, Suppl. (Roy Coll. Path.), 4, 65-72

Tissue fuel and weight loss after injury'

J. M. KINNEY, J. H. DUKE, Jr., C. L. LONG, AND F. E. GUMPFrom the Department of Surgery, Columbia University College ofPhysicians and Surgeons, New York,USA

In physiological and metabolic studies it is com-mon to refer to a mythical 'average' or '70 kg'man. It is useful to consider how this averageadult individual would respond to injury asjudged by the literature on injury of the pastdecade, with particular attention to the ideaswhich pertain to the supposed energy and fueldemands of this individual. The most commonfeature of the injured person is a period of promptweight loss, the rate of which is roughly propor-tional to the severity of the injury. Extra demandsare placed on vital organs. Nitrogen excretion isincreased, reflecting protein breakdown. Thesepostinjury changes are consistent with the conceptthat injury produces large increases in the level ofresting metabolism. Such increases in the demandfor tissue fuel occur at a time of reduced calorieintake, hence a large weight loss is to be expectedas the body consumes it own tissue for fuel. Ifbody protein is considered to be a primary energyreserve of the body, then extra nitrogen ex-cretion would naturally follow the breakdownof protein to meet these extra fuel needs. Sev-eral authors have suggested calorie expendituresof 5,000 to 6,000 calories per day (approximatelythree times normal) following a major injurysuch as an extensive burn (Artz and Reiss,1957; Moore, 1959). Extreme weight loss afterinjury presumably reflects the loss of both pro-tein and adipose tissue in orer to meet suchlarge energy demands. In addition to the in-creased oxidation of protein and fat, there issome decrease in tolerance to exogenous glucoseand perhaps a tendency to hyperglycaemia. Thishas been termed the 'diabetes of injury' and hasbeen interpreted as a reduction in the capacity tooxidize glucose.

Cuthbertson divided the response to injury into

'This work was supported in part by the US Army MedicalResearch and Development Command, contract no. DA-49-193-MD-2552, and the National Institute of General MedicalSciences, grant no. GM-14546-04, and the Hartford Foundation.

an 'ebb and a flow' phase (Cuthbertson, 1942).The'ebb'period was considered the period ofdiminished vitality and metabolism with circulat-ory deficiency as its central feature and occurringimmediately after the injury. The 'flow' period wasconsidered the period of increased metabolism or'traumatic inflammation' which was considered tobegin in 24 to 48 hours after the injury and wasassumed to correspond to an inflammatorydefence and removal of necrotic tissue. This flowphase of convalescence was observed to beaccompanied by an increase in blood sugar andbody temperature, as well as increases in pulse andrespiration and probably increased activity of thehypothalamic-pituitary-adrenocortical axis withdepletion of body protein.Moore (1953) subdivided the 'flow' phase of

convalescence after injury into an early orcatabolic phase lasting three to seven days afterelective operation and a longer period after majorinjury and sepsis, and then a 'turning point' of afew days with a reduction in nitrogen excretionand weight loss, followed by weeks of anabolismwith restoration of protein stores, adipose tissue,and general vitality. The metabolic response inthe posttraumatic period is based on the type andextent of the injury and the previous health of thepatient. As an approach to grading the severity oftrauma, a 'scale of 10' has been proposed (Mooreand Ball, 1952). The repair of a hernia would beregarded as 1 or 2 on this scale, whereas theextreme injuries such as major burns wouldqualify as 9 or 10. In the middle ranges would beordinarily elective abdominal surgery, such assubtotal gastrectomy or colectomy.

Weight Loss after Injury

Mild to moderate degrees of weight loss are socommon that careful efforts to monitor weightloss are often lacking in hospital care. It is

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J. M. Kinney, J. H. Duke, Jr., C. L. Long, and F. E. Gump

assumed that tissue function is not restricted bymild weight loss and that the loss can be restoredwithout difficulty as convalescence progresses.At the opposite extreme is the prompt but non-specific worry of the clinician when faced with thepatient having undergone extreme weight loss.Studley was among the first to call attention tosome of the implications of weight loss in pre-operative patients (Studley, 1936). In a study of 46patients operated upon for chronic ulcer diseasehe found that the percentage of preoperativeweight loss was the only factor thatcorrelated withoperative mortality rates. The mortality rate was33% in those patients who had lost more than20% of body weight before operation. In thosewho lost less than 20% of their normal weight themortality was 3.5 %. Between the lack of concernwith lesser degrees of weight loss and the worryover extreme loss is a large and ill defined rangeof weight loss whose development is only slowlynoticed, where the composition of tissue loss isnot clear, and the metabolic significance remainsuncertain.The extent of weight loss which has been

reported as a result of partial starvation providessome background for considering weight loss afterinjury. The nutritional literature contains manyreports of the weight loss of civilians, whichreached 10-20% of body weight when subjectedto the food restrictions of wartime. Famineconditions and wartime prison life have beenreported to cause 15-30% weight loss withoutbeing lethal. The cachexia of late starvation, suchas in certain concentration camp victims, wasassociated with the loss of 30 to 45% of bodyweight. Krieger (1920) attempted to show that alethal degree of weight loss existed from starvationalone and suggested that 40% loss was lethal inacute starvation and 50% in semi-starvation.Keys and others (Keys, Brozek, Henschel,Mickelsen, and Taylor, 1950) reviewed thisconcept and emphasized that such figures couldonly represent rough approximations at best. Itappears that underlying oiganic disease usuallydecreases the extent of weight loss from starvationwhich can be survived, and there is some reasonto believe that acute surgical conditions furtherdecrease the tolerance to prolonged weight loss.The weight loss after injury is usually due to a

combination of decreased dietary intake and avariable increase in basal energy expenditure. Theextent of weight loss has been shown by manyworkers to be influenced by the patient's sex, bodybuild, the preoperative nutritional status, thedegree of injury, and the presence of complicatingfactors such as infection. Our experience withadult surgical patients suggests that loss of weightbetween 5 and 10% occurs after mild, uncompli-cated forms of injury such as elective operation.Intermediate levels of weight loss, from 10 to 20 %,occur within four to six weeks after more severeinjury, particularly if involving multiple fracturesor major sepsis. If there is continuing inflam-

mation, such as active peritonitis, drainingfistulae, or invasive infection from an infectedburn surface, the loss of body weight will reach20 to 30%. Severe tissue wasting will be evidentunless obscured by water retention. Weight lossbeyond 30% represents precachexia with increas-ing trouble from weakness, decubitus ulcers, andjoint contractures. Death is often associated withbronchopneumonia.

Composition of the Adult Body

An approximate idea of the normal compositionof the adult body is necessary to understand theweight loss which occurs after injury. Classicinformation about the chemical composition ofthe human body has depended upon the analysisof postmortem tissues. In the last few decadesmethods have been developed which permitestimates of the body composition of the livingsubject. These techniques have largely beendiiected toward the calculation of the bodycontent of fat or water. Fat is an anhydrous tissuewith a lower density than lean tissue. Therefore, ifthe density of the whole body can be measured byimmersion (Buskirk, 1961) or by pneumatic meansin a chamber (Siri, 1961) an estimation of bodyfat can be made. Another method which is morefeasible for the study of the ill or injured patientinvolves an injection of a tracer material which isdistributed throughout the body water and allowsthe calculation of body content of the givenmater ial from dilution of the tracer(Moore, 1946).In order to convert the value for total body waterto the value of fat-free tissue in the body, thepercentage of water in lean tissue must be known.The studies of Pace and Rathburn (1945) haveshown that fat-free tissue normally contains closeto 73% water by weight. Thus the fat-free bodyweight obtained from isotope dilution can besubtracted from total body weight to arrive at fatcontent. The factor of 73% water in fat-free tissueprobably has some variation in disease and injury.No methods are currently available for the directdetermination of the amount ofprotein or skeletonin the body weight (Baker, 1961). But evidencefrom many lines of study suggest that the bodycomposition presented in Fig. 1 is a reasonableapproximation of that which is present in anaverage, healthy adult male weighing 70 kg. Thetotal mineral content of the body, largely foundin the skeleton, represents 3 to 5% of the totalbody weight. This amount is not only small butalso relatively static when compared with thechanges occurring elsewhere in the body. Theremaining 95% of the body can be convenientlyregarded in two phases: the aqueous phase,amounting to approximately 55 %, and the organicphase, amounting to approximately 40% of totalbody weight. The organic and the aqueous phasesof body composition will be discussed separately,but it is important to remember that the metabolic

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Tissue fuel and weight loss after injury

40%l.,,,GLYCO~GENCOG DEPOT:.,.11 kg. ~FAT

TOTAL550/ BODY

oWATER

5%0/MINERALS

Fig. 1 The approximate proportions ofaqueous andorganic phases are shown for the body composition ofan average 70-kg adult male. The smallfraction ofbody weight (3 to 5 %) shown for minerals is largelythat of the skeleton.

machinery or 'body cell mass' is a combination oforganic materials together with intracellular waterand electrolytes. In terms of body composition thebody cell mass (Moore, Olesen, McMurrey,Parker, Ball, and Boyden, 1963) appears toinclude tissue glycogen and a major portion, butnot all, of the total body protein. Therefore it is thebody cell mass which is constantly convertingoxygen and foodstuffs to carbon dioxide, water,work, and heat. It seems probable that the amountof average turnover of this body cell mass bears afundamental relationship to alveolar ventilation,cardiac output, and resting metabolicexpenditure.Somewhat over half of the organic material in

the body is shown as fat. A body fat content of17 kg represents 24% of the total body weight. It isrecognized that fat can vary from 10 to over 40%of total body weight. The fat content of healthyadults normally increases with age from approxi-mately 10% at the age of 20 years to 25 or30% atthe age of 55 years. Women are usually somewhatfatter than men. Carbohydrate is present in thehuman body in small amounts only, approxi-mately 300g of glycogen being present in liver andmuscle and in addition 10 to 20 g of glucose in theextracellular water. Therefore the total carbo-hydrate provides less than 1,500 calories andamounts to less than 1 % of total body weight. Aprotein content of 11 kg in the representativeadult male is an estimate based on analyses ofindividual tissue and calculations by difference,utilizing many human studies, of the content ofbody fat. The amount of skeletal material and leantissue and perhaps a small amount of structurallyimportant fat appear to be genetically controlledfor the individual. But the total amount of fat is avariable segment of body composition, since itreflects the voluntaryalterations ofenergybalance.

Loss of body weight following operative orphysical injury is so common that the metabolicdynamics involved and the potential consequences

67

that may ensue have failed to receive seriousconsideration. It was not until Cuthbertson'spioneerin,g observation (1932) of the excessiveexcretion of urinary nitrogen, sulphur, andphosphorus by patients who had sustainedfractures oflong bones that any significant analysisofposttraumatic weight loss was attempted. Whenan average 70-kg man loses 15 kg, the varioussegments of his composition do not share equallyin this weight loss (Moore, McMurrey, Parker,and Magnus, 1956). The total body water showssmall decreases in absolute amount, while therelative amount of water may increase. The extra-cellular space shrinks with acute weight loss. Bycontrast, chronic weight loss is associated withintracellular depletion. Acute illness and traumaare accompanied by the accumulation of waterand salt. Water accumulates in excess of sodium,resulting in hypotonicity. This response is ofparticular importance in understanding the bodycomposition ofthe non-obese patient who has lostmore than 10% of his body weight from a majorinjury with the associated partial starvation. Theprincipal decrease occurs in the intracellularportion of the body, mainly represented by pro-tein and cell water, together with a significant lossof fat. The extracellular space shows a relative, oreven an absolute, increase in volume. The bodybehaves as though protection from chronic weightloss can be provided by enlarging the extracellularspace as the body cell mass shrinks. The composi-tion of the blood volume is an excellent indicatorof the change in total body composition, since thedecrease of the body cell mass is reflected by adecrease in red cell volume, and the abnormalenlargement of the extracellular water is evidencedby an abnormally large plasma volume. Becausethese changes are in opposite directions, the totalblood volume is often equal to the normal amountfor this person in health.Any metabolic behaviour which is thought to

occur after injury must account for the extent ofthe weight loss which is commonly observed. Theideas from the literature indicate that the weightloss is explicable on the basis of injury causing alarge increase in energy expenditure, and thereforebody substance, particularly protein, is torn downto provide the extra fuel which is required. Thisformulation is based on a large volume of dataabout weight loss and nitrogen loss after injurywhich in general shows a correlation between therates of nitrogen loss and weight loss. Maximumrates of loss of both nitrogen and total weightoccur together (excluding transient diuresis), andit is rare for sustained weight gain to begin beforea positive nitrogen balancehas been achieved. Suchobservations are entirely consistent with the ideathat protein serves as a major energy reserveduring injury and sepsis. Thus measurements areneeded to determine what are the increasedcalorie needs after injury or sepsis, and whatcalorie contribution is made by the protein break-down which can be shown to occur.


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Energy Requirements after Injury

Because of the central role of energy requirementsafter injury in determining the amount of bodytissue required for fuel and also the caloriccontribution of tissue protein to these energydemands, our studies began with efforts tomeasure the resting metabolic expenditure aftervarious forms of injury and infection. No chambercalorimeters have been designed for the directmeasurement of body heat loss which would allow

A

D

appropriate professional care of the critically illpatient. Therefore we have turned to indirectcalorimetry as a way of measuring theamountandcomposition of each type of foodstuff beingmetabolized. This involves measuring the intakeof oxygen, the output of carbon dioxide, and theexcretion of nitrogen. The clinical importance ofmeasuring metabolic expenditure under nonbasalconditions had led to efforts at simplification, butthe assumptions and restrictions of the modifiedmethods have made them undesirable for theaccurate study of acutely injured patients. Certaintechniques require a degree of isolation of thepatient which prevents close professional carewhile the patient is being studied. Therefore asystem of continuous measurement of gasexchange in acutely ill patients has been designedfor use without a tight-fitting mask or mouthpieceor other attachment to the upper airway. Itinvolves a closed system using a rigid, transparenthead canopy (Fig. 2) which is practical andcomfortable for long study periods (Kinney,Morgan, Domingues, and Gildner, 1964). A light-weight plastic neck seal provides a leak-proofconnexion to the canopy, which is ventilated witha continuous stream of conditioned air. The airleaving the canopy is passed through pipes in thewall to a gas analyzer, located in another room,where flow and gas concentrations are continu-ously monitored. A unique calibration systemallows routine measurements of gas exchange to bereliable within ± 5 %, and often within ± 3 %.

Experience with this equipment in the study ofover 200 patients with various surgical conditionshas allowed the establishment of ranges of increasein resting metabolic expenditure relative to thepredicted basal metabolic expenditure of anindividual of a given size, sex, and age. The normalrange for average adult males is considered to be± 10% of the predicted normal value from BMRtables, as shown in Figure 3. Uncomplicatedelective operations are followed by no significant

Fig. 2 Continuous measurement ofgas exchange andexpired radioactivity can be performed without thedifficulties ofa tight-fitting mask or mouthpiece,utilizing a transparent, rigid head canopy. The canopyis ventilated with air which is continuously analyseddownstream with equipment located in an adjacentroom. The steps involved in fitting a lightweightplastic neckseal between the patient and canopy areshown here. Reproduced with kind permission of thepublisher from Cuthbertson (1932).

100-

+90 -

*80 -

*70 -

+60-

+50 -

+40 -

+ 30-+ 20-+ 10-,0 -t

-10-\

MAJOR BURNS

PERITONITIS

1MULTIPLE FRACTUR

ELECTIVE OPERATION(no signif icont

?R change)

Fig. 3 The ranges of increase in resting metabolicexpenditure to be seen in well nourished adult malesfollowing various forms of injury and sepsis. Theresponse to these conditions is less in the female, in theelderly, and in the poorly nourished individual.


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Tissue fuel and weight loss after injury

alteration outside of the ± 10%ofthepreoperativevalues. Major skeletal injury commonly results inincreases of 10 to 20% above normal for one tothree weeks, followed by a reduction to values of10 to 20% below normal as a reflection of thetissue depletion which has occurred by that time.Infection in a major serous cavity usually producesincreases of 15 to 50% above normal, and someelevation above normal will remain as long asinflammation is present, despite tremendoustissue depletion and weight loss. The only form ofinjury that has sustainedlevelsofhypermetabolismabove these ranges is the extensive burn, where themetabolism may remain from 40 to 100% abovenormal for weeks at a time.These levels of increased metabolism following

injury are doubtless of great significance to thebody, but do not reach the levels of hyper-metabolism (5,000 to 6,000 Cal/day) which havebeen suggested in the surgical literature. Themeasured increase in energy expenditure is notlarge enough alone to account for the serious,prolonged weight loss in the range of 400 to 900 gper day which is known to occur after majorinjury. Therefore it becomes increasingly import-ant to get an understanding of the daily balancebetween protein and non-protein sources of bodyfuel, and to examine the associated water losscontributing to this rate of weight loss. This canbe done with four or five measurements of gasexchange each waking day when calculated interms of a resting gas exchange for each 24 hours.This is combined with the nitrogen excretionvalue to calculate the daily resting non-proteincalorie expenditure using the table of Zuntz andSchumberg as corrected by Lusk (1928) as inFigure 4. In order to measure the caloric expendi-ture of patients out of bed, a portable headcanopy was designed which allowed for continu-ous gas exchange while sitting, standing, or walk-ing under ward conditions. Such measurements innormal volunteers revealed remarkable similaritiesin the percentage increase of caloric expenditure

FROM WEIGHED FOOD INTAKE *! CALORIC

a5 x 4 -~CAL. PROtEIN UTILIZED-LIZEN -5.92L 02 f.4J5L CO2) T

-PROTEINC02 m 24HR. NOIY-PROT. UO 'Er....U/L /ZAr/"-PROTEIN 02 a 24tR.NON-PROT. 0l

Fig. 4 The daily balance of calories and theapproximate balance for each foodstuff is obtainedcomparing caloric intake with caloric expenditureobtainedfrom multiple measurements of resting gasexchange combined with nitrogen excretion.

above resting values. These increases were in therange of 7% for sitting, 17% for standing, and145% for walking in the hospital corridor at arate of 1-2 to 1-5 miles per hour. The caloricexpenditure during walking was 0.039 Cal/min/kg(Long, Kopp, and Kinney, 1969). Detailed activitysheets were recorded by the nurses for periods upto 23 days on six patients. It was found that dur-ing a 24-hour period the patient was supine 50 to80% of the time and spent less than 10% of theday walking. When these activity figures wereconverted to calories it was found that the pre-operative activity was approximately 20%greater than resting values. The correspondingvalue dropped to only 5% for the first few daysafter operation, and then gradually returned to20% by 12 to 14 days.

Tissue Composition of Weight Loss

A study was undertaken to examine the contribu-tion of tissue components of the weight loss thatoccurred in lOpatients as a result ofuncomplicatedoperation (Kinney, Long, Gump, and Duke,1968). Changes in daily weight were measured ona hydraulic bed scale, protein content by nitrogenbalance, and fat content by indirect calorimetry.The total daily calorie balance was determined bysubtracting the total metabolic expenditure fromthe caloric intake. The non-protein calorie balancewas the difference between the total caloriebalance and the calories associated with proteinloss. The non-protein calorie balance was thendivided by a factor of 9.3 to determine the dailyloss or gain of body fat. The nitrogen balance foreach day was converted to dry protein using afactor of 6 25. In order to calculate the hydratedlean tissue equivalent, a moisture content of 75%was used.

This group lost approximately 6% of theirstarting weight within 10 days after operation. Fatprovided 75 to 90% of the calories while proteinaccounted for the remainder, as shown in Figure 5.The contribution of water to this weight loss wasfound to be in excess of the predicted quantity forboth men and women. The magnitude of the waterloss did not become evident until the second four-day period after operation which suggested adefinite antidiuretic influence over the first threedays. Continued water loss was observed in manypatients during the second postoperative weekwhile protein restoration was under way. Thecalories derived from this weight loss were un-expectedly low in the men (1,584 Cal/kg) as aresult of excessive water loss and a relatively highprotein to fat utilization. From such observationsit is evident that weight loss cannot be used topredict caloric expenditure and hence is not anappropriate guide to postoperative nutrition.Another group of surgical patients was studied

to determine the proportion of caloriessuppliedbyprotein after varying degrees of injury (Duke,

CALCULATIONS

24 HR. URINE N x 6.2(1gm. Urine

24 HR. CO PRODUCTIONS24:iR. 0 UTILIZATION-



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J0rgenson, Broell, Long, and Kinney, 1970).Patients undergoing elective operation weresimilar to the normal subjects with protein sup-plying an average of 15% of the caloric expendi-ture. Protein supplied approximately 20% ofcalories in the tissue fuel ofsix patients withmajortrauma and sepsis, while a similar increase innitrogen excretion of four patients with majorburns averaged only 14% of the resting caloricexpenditure, since the latter was elevated to anaverage of nearly 60%. Therefore, protein (oramino acids) provides only 12 to 22% of thecaloric expenditure, even in the forms of injury

MALE FEMALEWEIGHT CALORIES WEIGHT CALORIES

100

EXCESS PROT EXCE-SS 'PO

WATERWATER

i TISSUE

1584 KCAL/KG. 3105 KCAL/KG

Fig. 5 The components ofpostoperative weight lossover 10 days are expressed as percentages offat,protein, and water. The percentage of total caloriesderivedfrom fat approximates 80 to 90% of the totaldespite contributing only 10 to 30% to the weight loss.Reproduced with kind permission of the publisher fromLusk (1928).

GLYCOGEN DEPOT

PROTIf FA17 k~s

GLUCOSE-6-PO4 =GLUCOSEBL

TRIOSE-PO4 NEUTRAL FAT

11 t I+1AMINO ACIDS < - P

UREA

FATTY ACI

C4.

k Cs

Fig. 6 An abbreviated diagram of the maof intermediary metabolism which interconthree foodstuffs. See text for discussion ofloss (largely urea) after injury which is pr£related to mechanisms ofglaconeogenesistotal demands for two-carbon fuel.

where the nitrogen excretion per day is signi-ficantly increased. Thus, it seems that thenitrogen loss after injury must be occurringfor reasons other than merely to provide extracalories.Our findings are in agreement with those of

many other investigators who have noted that therate of weight loss tends to parallel the extent ofnegative nitrogen balance. The apparent correla-tion between weight loss and nitrogen loss can beexplained partly on the basis of both the amountof tissue used for fuel and the proportion of fat tolean tissue in the mixture. Fat is an anhydrousform of fuel with approximately 9 Cal/g, whilelean tissue has only approximately 1 Cal/g(Kinney, 1959). This is because body proteinexists in the body with approximately 3 parts ofwater, hence the 4 Cal/g of dry protein becomes1 Cal/g of hydrated lean tissue when body proteinis degraded following injury. Therefore, the weightloss associated with major injury or sepsis willhave a relatively high proportion of hydrated leantissue in the fuel mixture when considered byweight, whereas, when considered by caloriecontribution, the hydrated lean tissue contributionis only 12 to 22% of the entire resting calorieexpenditure. Thus, the extreme weight loss ofinjury and sepsis is not due to the huge needs forfuel in the metabolic furnace, but rather the bodyis meeting modest increases in energy demandswith a low energy fuel that requires more fuel(and hence has a faster weight loss) to meet what-ever calorie deficit exists.The idea that body protein is the major, or

even a good, source of calories whenever the bodyis faced with large increases in resting metabolismfollowing injury is not correct. Hence, explana-tions for the nitrogen loss after injury must besought in alterations of intermediary metabolicpathways other than the final fuel mixture foroxidation.

Intermediary Metabolism after Injury

The pathways of intermediary metabolism be-IDS tween the content of the three major foodstuffs in

the adult male body are shown in abbreviatedform in Figure 6. From the previous discussion it

- KETONE appears that the tricarboxylic acid cycle, shown in-*BODIES the lower right corner of the diagram, has onlymodest increases in its need for two-carbon fuel

cC after injury and sepsis, and that protein or aminoacid breakdown is a poor source of such fuel. Fatfrom adipose tissue stores appears to be mobilizedand oxidized without difficulty to meet whateverdemands occur for extra calories as a result ofinjury. Therefore, one is left with the question as

nrcpatheways to the meaning of the extra nitrogen excretion seen

nitrogen after injury and sepsis.obably more The pathways of intermediary metabolism inthan to the Fig. 6 are deliberately oversimplified to empha-

size that most amino acids yield carbohydrate



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Tissue fuel and weight loss after injury 71

intermediates or are 'glucogenic' on deamination.It appears that while fatty acids can provide two-carbon fragments readily for general tissue fuel,they cannot be used to provide a net gain of carbo-hydrate intermediates, glycogen, or circulatingglucose (Coleman, 1969). Therefore, in an actualor threatened situation of energy deficit, fat storescan be drawn upon for calories, but proteinrepresents the only sizeable reserve for carbo-hydrate intermediates-something which is alsocritical for survival.The changes in carbohydrate metabolism in the

later phases after injury are not as well delineatedas in the shock phase before resuscitation. Severalinvestigators have shown that there is a tendencytoward a diabetic-like glucose tolerance curvefollowing elective operation (Hayes and Brandt,1952) and that this is more marked after severeinjury (Howard, 1955). This tendency towardhyperglycaemia and glucose intolerance duringconvalescence following injury has resulted insuch terms as 'traumatic diabetes' (Thomsen,1938) and 'diabetes of injury' (Drucker, Miller,Craig, Jeffries, Levy, and Abbott, 1953). Thisterm suggests a relative or absolute lack of insulinactivity and presumably a decrease in the levels ofblood pyruvate and lactate after injury (Drucker,Craig, Hubay, Davis, and Woodward, 1961). Thework of Drucker and his associates (Drucker,Craig, Kingsbury, Hofmann, and Woodward,1962) has suggested a partial block in thepathways leading from pyruvate to two carbonfragments during the later phases of convalesc-ence as well as the evidence for such changesduring the shock phase.The role of glucose metabolism in injury is

further confused by the growing recognition of asyndrome first reported by Evans and coworkers(Evans and Butterfield, 1951) in occasional burnpatients without any diabetic history, who devel-oped unexpected lethargy and coma and werefound to have marked hyperglycaemia withoutacidosis. During the past decade there has beengrowing awareness that lethargy, coma, and evendeath may occur occasionally in diabetic patientswithout explanation and has been given the name'non-ketotic, hyperosmolar coma' (Ashworth,Sacks, Williams, and Byrne, 1968). One explana-tion has been that a sudden increase in circulatingcorticosteroids could inhibit the action of insulin,but most of the recorded cases have not been onsteroid therapy. There appears to be an increasingincidence of this syndrome in acute surgicalpatients, when receiving large amounts of intra-venous glucose.The evidence for the idea that injury inhibits the

oxidation of glucose has been indirect in man orlimited to special circumstances in animal or tissuestudies. Tracer studies with 14C-glucose have beenemployed with a mathematical model developedby Dr Jordan Spencer to relate blood and breathspecific activities and the rate of CO2 productionto the rate of glucose turnover and oxidation in

surgical patients (Spencer, Long and Kinney,1970). To date, 35 glucose runs have been made,including 14 volunteers (Long, Spencer, Kinney,and Geiger, 1970a) or patients undergoing electivesurgery. -The studies have demonstrated thatglucose oxidation is essentially unchanged inminor degrees of trauma which may be expectedto reduce glucose tolerance and perhaps increasethe resting level of blood sugar. However, in thecritically ill patient with a stable circulation andsignificant hyperglycaemia, our measurementsindicate that such a patient has some increase inglucose oxidation as well as an increased glucoseturnover in the bloodstream (Long, Spencer,Kinney, and Geiger, 1970b). We have alsodemonstrated that the hepatic manufacture andrelease into the bloodstream ofnew glucose, whichis normally inhibited by the administration ofapproximately 6 g of glucose per hour intraven-ously, is no longer inhibited by the administrationof this amount ofglucose to the patient aftermajorinjury. The alteration in the control system bywhich the liver ceases to turn off this process forglucose manufacture is of both theoretical andpractical interest, and is a subject of continuingstudy.At the present time, neither the utilization of fat

nor the breakdown of hydrated lean tissue withexcretion of the associated water and nitrogen isadequate to explain the weight loss seen afterinjury. The additional reason for the rapid weightloss is that water in excess of tissue fuel is beingexcreted. This may be associated with the normalunloading of previously retained water, or toabnormal renal function. Another factor is thetendency seen in studies of starvation (Kekwickand Pawan, 1956) and paediatric nutritionalstudies (Holt, 1957) where the body excretes extrawater for several days after shifting from a highcarbohydrate to a high fat fuel mixture regardlessof whether the fat is from the diet or from tissuestores as in starvation. The reverse phenomenonappears to occur when the body returns to a highcarbohydrate diet. Analysis of the tissue composi-tion of weight loss in patients following electiveoperation revealed that 35 to 45% of the weightloss was water in excess of that expected from thehydration of the measured protein breakdown(Kinney et al, 1968).

References

Artz, C. P., and Reiss, E. (1957). The Treatment of Burns.Saunders, Philadelphia.

Ashworth, C. J., Jr, Sacks, Y., Williams, L. F., Jr, and Byrne, J. J.(1968). Hyperosmolar hyperglycemic non-ketotic coma:its importance in surgical problems. Ann. Surg., 167, 556-560.

Baker, P. T. (1961). Human bone mineral variability and bodycomposition estimates. In Techniques for Measuring BodyComposition, edited by J. Brolek, and A. Henschel, p. 69.National Academy of Sciences, National Research Council,Washington, D.C.

Buskirk, E. R. (1961). Underwater weighing and body density: Areview of procedures. In Techniques for Measuring BodyComposition, edited by J. Brolek and A. Henschel, p. 90.National Academy of Sciences, National Research Council,Washington, D.C.


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Coleman, J. E. (1969). Metabolic interrelationships between carbo-hydrates, lipids and proteins. In Duncan's Diseases ofMetabolism, Vol. 1, Genetics and Metabolism, 6th ed.,edited by P. K. Bondy, and L. E. Rosenberg, pp. 89-198.Saunders, Philadelphia.

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