Am J C/in Nuir l992;55:l 135-41. Printed in USA. © 1992 American Society for Clinical Nutrition 1135

Plasma amino acid concentrations in geriatric controland hip-fracture patients13

Calvin L Long, John W Geiger, Ernest W Richards, John M Akin, and William S Blakemore

ABSTRACT Changes in plasma amino acids, 24-h nitrogenbalances, and resting metabolic expenditures (RMEs) were mea-

sured in 10 geriatric patients (aged 70-92 y) with hip fracture 1

d after surgical fixation during both a 24-h fasting state and

while receiving total peripheral parenteral nutrition (TPPN) for

24 h at 1.5 g amino acids - kg’ - d’ and 29-30 kcal - kg� - d’

and compared with 19 healthy volunteer subjects (aged 70-84

y). RME and 24-h urinary nitrogen losses were also elevated in

the trauma patients during both fasting and TPPN. Positive ni-trogen balances were evident in both groups during TPPN.

Plasma total amino acid concentration was significantly lowerin the trauma patients because of lower plasma concentrations

ofthe nonessential amino acids. Phenylalanine and methionine

concentrations were significantly higher and lysine lower in

the trauma group. In addition, evaluation of the essential

amino acid ratios after fasting and TPPN reveal that there are nolimiting amino acids during TPPN. Am J C/in Nuir 1992:55:

1 135-41.

KEY WORDS Plasma amino acids, hip fracture, geriatrics,

trauma

Introduction

Although circulating plasma amino acids constitute a smallportion of the free amino acid pool in the body, their concen-tration patterns are reflective of the differences that occur in

whole-body protein and amino acid metabolism both during

starvation and after injury. As such, these patterns have provideduseful information about the nutritional status of fasting man.

Pattern alterations have been reported in humans and animalswhen there is a deficiency of any one or more of the essential

amino acids (EAAs) (1-5), a dietary imbalance of amino acids(6, 7), or a deficient intake of protein (8, 9). Although the lit-

erature on plasma amino acid profiles in normal, injured, and

septic young adult populations is numerous (4, 10-1 5), there

have only been a few studies in healthy elderly populations (16-

19) and even fewer in injured geriatric patients (20).This study was designed to compare the fasting plasma amino

acid patterns of normal and traumatized geriatric patients and

to assess the adequacy of total peripheral parenteral nutrition

(TPPN) as shown through potential limiting amino acid patterns

and nitrogen balance.

Subjects and methods

The subjects studied consisted of 19 volunteer female geriatric

control subjects and 10 female geriatric hip-fractured patients

(Table 1). On enrollment, control subjects were admitted to the

research unit at the Baptist Medical Center at 0800, with in-

structions not to eat after 2 100 the night before admittance.

Hip-fractured patients were admitted to the emergency room,

diagnosed, and scheduled for hip fixation, usually the next

morning. Written informed consent was obtained from all in-

dividuals before the evaluation. The protocol was approved by

the Institutional Review Board of the Baptist Medical Centers.

The control group was aged 75.2 ± 1 . 1 y (i ± SE) and the

trauma group 80.9 ± 2.3 y. At the time ofthe study none of the

control subjects or patients were septic, were diabetic, or pre-

sented with liver, renal, or malignant disease. Both control sub-

jects and hip-fractured patients were either living alone or were

part ofa functioning family group. The body weight ofthe controlgroup was 95% of the ideal weight for height vs 94% for the

trauma group.

After entering the protocol the control group received only

electrolytes by intravenous infusion for 24 h. The hip-fractured

group was placed on the protocol the morning after hip fixation

and received similar fluids for 24 h. This period was defined as

day one. At the start ofday 2, TPPN was initiated in both groups

for a 24-h period. The TPPN solution was prepared with 10%

Aminosyn (Abbott Laboratories, Chicago) and 50% dextrose with

added electrolytes, minerals, and vitamins at an infusion rate of80 mL/h. Five hundred milliliters of 20% lipid emulsion was

coinfused at 20 mL/h. This TPPN solution provided 1.5 g amino

acids/kg body wt and 12 1 .3- 125.5 U (29-30 kcal)/kg body wt.

The nonprotein kcal ratio ofglucose to lipid was 45:55.

At 0800 on the morning after surgical intervention, all patients

were placed on metabolic balance for calories and nitrogen. In

addition to the electrolytes on day 1 and TPPN on day 2, both

control and trauma groups were allowed oral intake of water

and/or caffeine-free diet soft drinks only. Oral intake by each

individual was strictly monitored by our research nurse and die-

titian. Anthropometric measurements were carried out on all

subjects and consisted of midarm circumference, calculated

� From the Department of Research, The Baptist Medical Centers,

Birmingham, AL.2 Supported by NIH grant ROl AG06635.

3 Address reprint requests to CL Long, Department of Research, TheBaptist Medical Centers, 701 Princeton Avenue, Birmingham, AL 35211

Received September 6, 1991.Accepted for publication December 4, 1991.

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1 136 LONG ET AL

TABLE 1Characteristics of control and hip-fracture patients

Variable

Controlpatients(n - 19)

Traumapatients

(n = 10) Pt

Age(y) 75.2± 1.1 80.9±2.3 -

Height(cm) 161.0± 1.3 161.8± 1.7 0.699Weight(kg) 56.8± 1.5 52.6±3.5 0.196Lean body mass (kg)� 36.4 ± 0.8 35.3 ± 1.4 0.453Body surface area (m2) 1.6 ± 0.02 1.5 ± 0.1 0.129Creatinine clearance on

day 1 (mL/min) 51.4 ± 3.1 61.4 ± 9.0 0.206Creatinine clearance on

day 2 (mL/min) 52.0 ± 3.3 62.4 ± 7.9 0.159

S � � SE.

t Control vs trauma patients (unpaired Student’s I test).� Determined from standard anthropometric measurements.

midarm muscle mass, and skinfold thickness of the biceps, tri-

ceps, supraihiac crest, and subscapula. Lean body mass (LBM)was determined from skinfold-thickness measurements and thestandard regression equations of Durnin and Womersley (21).

To estimate a nonactivity caloric balance, oxygen consump-tion and carbon dioxide expired were measured during the last4 h of both the first (day 1; fasting) and the second 24-h study

period (day 2; during TPPN) while the patients were still supine

with the system previously reported by Long et al (22). At least

three 20-mm measurements were made over the period between0700 and I 100; the measurements were averaged and extrapo-lated to 24 h. The caloric equivalent of oxygen consumed was

then calculated by using respiratory quotient (RQ) values from

the table of Lusk (23). Because the gas exchange was monitoredonly under resting conditions in the morning, the calories cx-pended represent the resting metabolic expenditure (RME) forboth the control and trauma patients.

Twenty-four-hour urine samples were collected from bothgroups during both the fasting and TPPN periods. Collection ofurine from the trauma patients was facilitated by Foley catheters(CR Bard, Inc, Covington, GA), which were used as part of thesubjects’ medical management. Total urinary nitrogen was de-

termined by microKjeldahl digestion, with the resulting am-

monia assayed by an alkaline phenol reaction by using an EncoreChemistry Analyzer (Baker Instruments, Allentown, PA) (24).Urinary urea nitrogen was determined enzymatically by using

the above analyzer. Blood urea nitrogen (BUN) was determinedfrom the plasma urea concentrations obtained from the respec-tive amino acid profiles during each nutritional state (fastingand TPPN). Nitrogen balance was determined as the differencebetween 24-h total nitrogen intake and 24-h total urinary nitro-gen losses. Because most patients who enrolled in these studies

were without any other significant sources ofnitrogen excretion,insensible nitrogen losses were not included in the nitrogen bal-

ance. To verify the completeness of 24-h urine collections aswell as to assess the respective creatinine coefficients of the twogroups of patients, each 24-h urine collection was analyzed forcreatinine by the Jaft�e reaction by using the Encore Chemistry

Analyzer. In addition, creatinine clearance was determined by

using the following formula:

(UV/P) X (1.73/A)

where U is the 24-h urinary creatinine concentration (mol/L),

V is the urine output (mL/min), P is the plasma creatinine con-centration (mol/L), and A is body surface area (m2).

Heparinized venous blood samples for amino acids, glucose,

insulin, albumin, norepinephrine, and epinephrine determina-

tion were obtained each morning either at the end ofthe fasting

or TPPN 24-h study period. The blood was centrifuged at 12350x g at 4 #{176}Cfor 10 mm and the plasma was transferred to separate

tubes and stored at -80 #{176}Cuntil analysis. The plasma for amino

acid analysis was deproteinized with 0.05 mL 60% sulfosalicylic

acid/mL plasma. After centrifugation the supernatant was filteredthrough a 0.45-�zm filter (Acrodise LC13, Gelman Sciences, Ann

Arbor, MI).A known portion ofthe supernatant was diluted with an equal

volume oflithium citrate buffer (pH 2.2) for analysis on a model

6300 Amino Acid Analyzer(Beckman, Palo Alto, CA). Standards

and samples were loaded into 50-�tl sample metering loops

maintained at 4 #{176}C.Four lithium citrate buffers ofdifferent ionic

strength and pH and a one-step temperature gradient were used

to separate the amino acids. A calibrated mixture ofamino acids

supplied by Beckman Instruments that contained most of the

amino acids found in physiological samples was used to stan-

dardize the analyzer. Known amounts ofasparagine, glutamine,

and tryptophan were added to this calibration mixture at the

time ofthe working-standard preparation. It was found that the

amino acids in these working standards were stable for > 1 mo

if kept at -80 #{176}Cwhen not in use. The actual procedures for

analysis of multiple samples were to analyze a standard at the

beginning ofthe run, one standard in the middle ofthe run, and

one at the end of the sequence. The coefficient of variation of

multiple plasma analyses was within 3. 1%. Plasma amino acid

ratios were calculated according to the method of Longenecker

and Hause (25) by using the minimum daily requirement for

EAAs reported by Rose (26).

Statistics

Results are reported as mean ± SE. Significant differenceswere evaluated by using the unpaired Student’s t test. A P value� 0.05 was considered statistically significant.

Results

Injured geriatric patients were evaluated in a fasting state 24h after surgical repair ofthe hip fracture (day 1). After day 1 the

patients received a 24-h infusion of TPPN (day 2). RMEs were

measured at the end of each period in the morning before any

activity by or to the patient. The control group was similarly

treated. The results in Table 2 show that the RME ofthe injured

group was significantly higher than that of the control group

when expressed on a body-weight basis (kJ - kg’ - d’) duringboth 24-h study periods. However, when the RME data are nor-malized to LBM as determined from anthropometric measure-

ments, this elevation in RME is no longer statistically significant.

Comparisons ofpredicted RME values from the Harris-Benedict

equation (kcal/d) to the measured values reveal a significant

elevation in RME (20%) in the trauma group.

The mild hypercatabolic response due to hip fracture in thegeriatric patient as revealed by urinary nitrogen losses normalized

to LBM is shown in Table 3. The losses during a 24-h fast (day

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GERIATRIC PLASMA AA CONCENTRATIONS 1137

TABLE 2Resting metabolic expenditures (RME) of geriatric patients after hip fracture and in control subjects during basal and during short-term totalperipheral parenteral nutrition (TPPN)

Day 1 (fasting) Day 2 (TPPN)

Control Trauma Control Traumapatients patients P� patients patients Pj�

Predicted RMEj

kJ/d 4761.5 ± 70.7 4463.6 ± 152.3 4761.5 ± 70.7 4463.6 ± 152.3kcal/d 1138.0± 16.9 1066.8±36.4 1138.0± 16.9 1066.8± 36.4

Measured RME

kJ/d 5044.4 ± 132.2 5304.2 ± 318.0 0.381 5174.5 ± 128.5 5344.4 ± 301.3 0.548kcal/d 1205.6 ± 31.6 1267.7 ± 76.0 1236.7 ± 30.7 1277.3 ± 72.0kJ.kg�.d� 89.5 ± 2.5 104.2 ± 5.4 0.012 92.1 ± 2.9 105.4 ± 5.9 0.031kcal.kg� .d’ 21.4 ± 0.6 24.9 ± 1.3 22.0 ± 0.7 25.2 ± 1.4lcJ.kg LBM’ #{149}d� 139.3 ± 4.2 150.2 ± 6.3 0.159 143.1 ± 4.6 151.5 ± 5.4 0.276kcal#{149}kgLBM� #{149}d’ 33.3 ± 1.0 35.9 ± 1.5 34.2 ± 1.1 36.2 ± 1.3

Percent difference frompredicted(%)� 6.1 ±2.8 18.5±5.1 0.030 9.0±3.0 20.0±6.1 0.078

5 1 ± SE.

t Control vs trauma patients (unpaired Student’s t test).� Determined by using the Harris-Benedict equation.§ Based on kcal/d only.

1) were greater in the trauma group than in the control group

but were not significant at the 95% confidence level. When the

control and trauma patients received 1 .5 g amino acids/kg for

24-h (day 2), nitrogen balances were positive in both groups;

however, the control group retained slightly more nitrogen than

did the trauma group.

Table 4 presents the mean ± SE of various plasma substratesand hormones. After the 24-h fasting period the trauma grouppresented with a significantly higher plasma glucose concentra-

tion as compared with the control group. During TPPN plasma

glucose concentration increased in both groups; however, the

greater increase in the trauma group was not significant. Asso-ciated with increased plasma glucose concentrations was a small

nonsignificant increase in insulin during the fasting period. Both

groups showed a threefold increase in insulin during TPPN.

Plasma albumin concentrations were significantly lower in thetrauma group than in the control group. The plasma norepi-nephrine concentration was the same in the control group during

TABLE 3

both fasting and TPPN; however, in the trauma group its con-

centration was significantly elevated above the control value in

both nutritional states-twofold during fasting and threefold

during TPPN. Epinephrine, although elevated in the trauma

group, was not statistically different from the control group dun-

ing either nutritional state.

Plasma concentrations ofindividual amino acids for the con-

trol and injured geriatric patient groups during both fasting and

TPPN are shown in Table 5. Focusing on the plasma concen-

trations of EAAs of the trauma patients as compared with the

control group after a 24-h fast, five of the EAAs were slightly

lower, two were significantly higher, and one remained un-

changed. A similar pattern was evident during TPPN. Of the

EAAs, significant differences were noted for phenylalanine, me-thionine, and hysine after trauma. The provision of TPPN in-

creased the concentration of the amino acids, that were present

in the infusate, compared with the fasting concentration. How-

ever, the concentrations of isoleucine, methionine, and lysine

Urinary nitrogen losses in control and hip-fracture patients during fasting (day 1) and during total peripheral parenteral nutrition (TPPN) (day 2)

Dayl Day2

Control TraumaControl Traumapatients patients Pt patients patients P�

BUN (mmol/L4 3.9 ± 0.2 4.4 ± 0.7 0.413 5.3 ± 0.2 6.9 ± 1.2 0.106Intake (mmol . kg LBM� . d’) 0 0 - 26.2 ± 0.6 28.0 ± 0.8 0.109Urinary losses(mmol#{149}kg LBM’ #{149}d’).� 10.4 ± 0.7 12.0 ± 1.1 0.208 17.3 ± 1.0 20.8 ± 0.8 0.028Balance(mmol.kg LBM’ .d�) -10.4 ± 0.7 -12.0 ± 1.1 0.208 +8.9 ± 0.9 +7.2 ± 0.8 0.234

S � � SE.

t Control vs trauma patients (unpaired Student’s t test).� Blood urea nitrogen.

§ Corrected for expansion of the nitrogen pooh by using the change in BUN resulting from the infusion of TPPN.

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S � � SE.

t� Significantly different from control: tP � 0.001, �P � 0.01, §P � 0.05.

1 138 LONG ET AL

TABLE 4Plasma substrate and hormone concentrations in control and hip-fracture patients

Day 1 (fasting) Day 2 (TPPN)

Control Trauma Control Traumapatients patients Pt patients patients Pt

Glucose (mmol/L) 4.4 ± 0.1 5.2 ± 0.3 0.007 6.2 ± 0.2 6.7 ± 0.5 0.246

Insulin (pmol/L) 79 ± 22 103 ± 20 0.49 1 325 ± 76 333 ± 32 0.940Albumin (g/L) 40 ± 1 28 ± 1 <0.001 40 ± 1 24 ± 2 <0.001Norepinephrine (nmol/L) 1.47 ± 0.18 2.53 ± 0.35 0.009 1.39 ± 0.13 4.04 ± 1.60 0.002

Epinephrine (pmol/L) 175 ± 33 257 ± 82 0.289 158 ± 38 289 ± 180 0.238

S � � SE.

t Control vs trauma patients (unpaired Student’s I test).

were significantly lower after trauma as compared with the con- shown in Table 6. After a 24-h fast, the total amino acid (TAA)

trol group. pool of the trauma group was significantly lower by 17% com-Of the nonessential amino acids (NEAAs) after a 24-h fast, pared with the control group. When TPPN was instituted the

significantly lower values were noted for alanine, glycine, serine, total amino acid pooh was expanded in both groups; however,glutamine, anginine, histidine, ornithine, and citrulhine after there was still a significant depression of this pool (20%) after

trauma. The only NEAA to show a significant elevation after a injury. This decrease in the total amino acid pool resulted from

24-h fast was tyrosine. Except for ornithine, identical patterns a significant depression of NEAA concentrations (28%) with nowere noted for the NEAAs after TPPN because of trauma. significant change in EAA concentrations (6.5%) compared with

The hypoaminoacidemia seen after trauma showed a distinct control subjects. During TPPN, significantly lower concentra-

pattern when the sum of EAAs and NEAAs were compared, as tions of both NEAAs and EAAs were evident.

TABLESPlasma amino acid concentrations in geriatric control and hip-fracture patients during fasting and TPPN5

Day I (fasting) Day 2 (TPPN)

Control Trauma Control TraumaAmino acid patients patients patients patients

�imo//L

Essential amino acidsVal 205.5 ± 9.2 194.5 ± 13.4 372.0 ± 21.6 330.2 ± 18.2

Leu 135.9 ± 7.6 126.3 ± 10.7 182.1 ± 16.1 156.6 ± 10.7the 61.8 ± 4.4 51.6 ± 4.8 134.2 ± 8.5 1 10.7 ± 7.2Phe 46.8 ± 1.6 64.5 ± 3.7t 90.8 ± 4.9 85.6 ± 6.2

Tyr 43.4 ± 3.7 44.1 ± 5.0 51.3 ± 3.4 58.9 ± 4.6

Met 15.9 ± 0.8 20.3 ± h.1j 62.0 ± 3.7 50.6 ± 3.2�Thr 80.4 ± 4.8 71.8 ± 3.5 176.1 ± 10.4 137.4 ± 9.8Lys 157.3 ± 7.7 124.9 ± l0.l� 198.1 ± 8.9 162.6 ± 8.9t

Nonessential amino acidsAla 223.5 ± 12.5 166.7 ± l0.lj 438.5 ± 27.8 335.1 ± l9.6�

Gly 242.9 ± 17.5 139.3 ± 6.7t 520.8 ± 43.8 334.9 ± l2.8tSer 83.1 ± 3.8 60.7 ± 3.7t 170.2 ± 10.1 1 1 1.9 ± 7.2tGln 523.9 ± 20.4 381.3 ± 21.8t 542.1 ± 25.0 369.9 ± 2l.6tPro 104.6 ± 4.5 101.8 ± 6.9 262.5 ± 19.0 266.6 ± 18.5Arg 60.6 ± 3.7 39.9 ± 2.7t 136.7 ± 8.7 93.5 ± 5.5tHis 64.2 ± 2.1 52.8 ± 3.8� 78.4 ± 3.4 63.9 ± 5.lf

Taurine 50.1 ± 7.6 46.1 ± 3.7 50.9 ± 5.0 39.9 ± 5.1

Glu 35.1 ± 5.3 23.1 ± 3.0 44.4 ± 4.6 24.8 ± 3.9fTyr 42.9 ± 1.9 56.2 ± 3.2t 39.7 ± 1.9 46.9 ± 3.7

Orn 57. 1 ± 2.3 40.8 ± 3.3t 83.5 ± 4.9 92.3 ± 5.8Citrulhine 28.0 ± 1.5 16.4 ± h.4t 31.0 ± 2.2 18.7 ± l.OtAsn 15.3±0.7 16.6± 1.2 8.0±0.8 10.4± 1.4

Cys 60.6 ± 1.7 57.9 ± 3.6 44.8 ± 2.5 41.9 ± 3.2

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GERIATRIC PLASMA AA CONCENTRATIONS 1 139

As shown in Table 6, plasma phenylalanine concentrations

in the trauma group were increased by 38% and lysine by 31%

and both were significantly greater than those in the controlgroup. During TPPN, phenylalanine concentrations were similar

in both groups but tyrosine concentrations were still significantlyhigher in the trauma group. The profile ofaromatic amino acids

after a 24-h fast showed a 26% elevation after trauma, whichwas highly significant. There were no differences in aromatic

amino acids during TPPN. The sum of the branched-chain

amino acids was lower but was not significantly different in eithergroup whether fasting or during TPPN. As noted, branched-

chain amino acids were nearly twofold higher in both groups

during TPPN.

The plasma ratio of branched-chain amino acids to aromaticamino acids was significantly lower in the trauma patients than

in the control group during both fasting and TPPN. This response

appears to be due to an increase in aromatic amino acid con-

centrations in the trauma group. The trend for branched-chain

amino acids is similar for both groups, fasted or fed, because

the ratio to TAA was the same. There were no differences in the

phenylalanine-tyrosine ratio during fasting or TPPN.

Comparisons of the concentrations of the individual plasmaamino acids during fasting and after feeding with TPPN provideinformation that can be used to assess the adequacy ofthe amino

acid mixture in the TPPN solution infused. The results in Table7 show that the ratio of each EAA (feeding to fasting ratio) in

the control and trauma groups are positive, indicating there areno limiting amino acids when Aminosyn was infused at 1 .5 g

amino acids . kg� . d’.

Discussion

The catabolic response to injury is recognized mainly as an

increased excretion of urinary nitrogen and a corresponding in-

crease in RME (22). Associated with these changes are charac-

teristic increases in blood glucose concentrations as well as in-

creases in various hormones after injury. The indices used to

TABLE 6

TABLE 7Limiting plasma amino acid ratios as a reflection ofthe adequacy of

amino acid infusions in geriatric control and hip-fracture patients

Amino

acidControl

patients

Trauma

patients

Leu +54 +37

Lys +74 +102Trp +123 +127

Ile +140 +112

Thr +230 +158Val +243 +200

Phe +245 +129

assess the magnitude ofinsult in the geriatric hip-fractured group

are assumed to be closely related to those used in younger adult

populations. The significant increased fasting hyperglycemia and

increased RME after fasting or TPPN suggest that these patients

were mildly hypermetabolic. Urinary nitrogen losses were slightly

greater in the injured group and were only significant during

TPPN. It appears that the efficiency of nitrogen retention is de-

creased in the aging process as reported by Jeevanandam et al

(20). Although renal function decreases with aging, the increasednitrogen loss after injury on a comparative basis is not due to a

differential renal dysfunction because creatinine clearance was

similar in both groups. Supporting this increased catabolic re-

sponse is the elevation in plasma catecholamines, which are as-

sumed to be, in part, responsible for the hyperglycemia observed

in injured patients.

The albumin concentrations shown in Table 4 suggest a mal-

nourished geriatric trauma population; however, these patients

were independent living alone or with family before the accident.

Albumin concentrations are unreliable as indicators of malnu-

trition because they have been shown to be significantly decreased

in younger populations after injury ( 15) and may account for

the majority of the decrease observed here. Mean 24-h urinary

Comparison of mean values of groups of amino acids in geriatric control and hip-fracture patients during fasting and TPPN5

Day 1 (fasting) Day 2 (TPPN)

Control TraumaControl TraumaGroup patients patients patients patients

�imo//L

TAA 2263.5 ± 64.1 1867.1 ± 69.3t 3640.9 ± 122.2 2885.2 ± 78.2tEAA 744.6 ± 24.3 697.8 ± 37.4 1266.6 ± 50.2 1086.8 ± 39.3�NEAA 1518.9 ± 56.2 1 169.3 ± 42.lt 2374.3 ± 96.4 1798.4 ± 67.lt

Phe 46.8 ± 1.6 64.5 ± 3.7t 90.8 ± 4.9 85.6 ± 6.2Tyr 42.9 ± 1.9 56.2 ± 3.2t 39.7 ± 2.0 46.9 ± 3.7�AAA 130.8 ± 5.6 164.7 ± 5.3t 181.8 ± 7.2 185.6 ± 9.4BCAA 403.2 ± 20.9 372.3 ± 27.8 688.2 ± 43.5 597.5 ± 34.7BCAA/AAA 3.31 ± 0.36 2.27 ± 0.l7� 3.95 ± 0.40 3.15 ± 0.21BCAA/TAA 0.18 ± 0.01 0.20 ± 0.01 0.19 ± 0.01 0.20 ± 0.01Phe/Tyr 1.12 ± 0.05 1.16 ± 0.05 2.41 ± 0.19 1.92 ± 0.18

5 1 ± SE. TAA, total amino acids; EAA, essential amino acids; NEAA, nonessential amino acids; AAA, aromatic amino acids; and BCAA,branched-chain amino acids.

ti� Significantly different from control: tP � 0.001, tP � 0.05, §P � 0.01.

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1140 LONG ET AL

creatinine excretion was similar between the control and traumagroups (12.5 ± 0.6 vs 13.4 ± 0.6 mg/kg body wt, respectively),

suggesting that muscle mass was not different between the two

groups.

A characteristic pattern ofplasma amino acid concentrationshas been described in the unfed stressed patient. The circulating

amino acid pool is a measure of the ongoing anabolic and cat-abolic processes associated with protein metabolism. An aminoacid that is in the diet in the smallest amount relative to itsrequirement, will generally show the greatest fall or smallest rise

in the postprandial plasma value. Conversely, plasma concen-trations of an individual amino acid that is provided in the

greatest excess of requirement is not often evaluated except in

the case ofinborn errors in amino acid metabolism. It is possible

that this latter case could also result from the inability of thebody to break down excess amino acids.

The observed patterns of plasma amino acid concentrationsin fasted injured patients are significantly altered compared withthe control group. The hypoaminoacidemia seen in the traumagroup during fasting and TPPN is due to a lower concentration

of NEAAs with a minimal change in EAAs. These differencesare similar to those reported by Jeevanandam et al (10, 20).

Note that this trend oflower NEAAs in the trauma group con-

tinued even while the patients were receiving TPPN. This de-creased efficiency of amino acid utilization may be unrelated tothe age of the individual because these investigators reportedsimilar responses in NEAAs in a younger-aged trauma group.The small change in branched-chain amino acid concentrations

in plasma of the hip-fractured patients suggests a minimal re-

sponse to this catabolic insult. Most reports show that they arestable or higher after skeletal trauma in young populations (1-

5); however, Jeevanandam et al (20) reported a 33% increase inbranched-chain amino acids in their geriatric trauma patients.

The variable nature of branched-chain amino acid concentra-tions is supported by the essentially unchanged plasma concen-trations after sepsis or injury, although there were profound in-

creases in intracellular concentrations. Whether geriatric patientsrespond similarly is yet to be determined.

The concentration of other EAAs, such as phenylalanine andmethionine, are reported to be elevated in stressed states (12,

15, 20, 27-30). The significantly higher plasma phenylalanine

concentrations in geriatric hip-fracture patients during fastingare typical ofthe hypercatabolic response. Phenylalanine is con-sistently elevated in injured patients and serves as a reliable index

of skeletal muscle catabolism (3 1). Although concentrations ofsome EAAs do not change after trauma, the phenylalanine re-sponse persists in trauma victims and is a good clinical indicatorof the magnitude of the insult. An increase in phenylalaninemay not be caused by a decrease in protein synthesis by thevisceral tissues (27), by altered renal clearance (3 1), or by a de-crease in phenylalanine hydroxylase in this elderly population,

but rather by an increased release ofphenylalanine from muscletissue under stress conditions, which appears to exceed its uti-

lization (rate ofdisappearance is less than the rate of appearance).

Tyrosine is synthesized from phenylalanine and the increased

concentrations are presumably maintained because of higherphenylalanine concentrations. Increased concentrations as well

as minimal changes in plasma tyrosine concentration have beenreported (1 1, 12, 15, 20, 28, 32) after trauma and sepsis. Assuch, the ratios of phenylalanine to tyrosine in stressed states

are generally higher because the phenylalanine concentrations

are elevated to a much greater extent than is tyrosine. We have

observed a 30% increase in plasma tyrosine concentrations that

was comparable to the increase in observed phenylalanine and

as such the ratios of phenylalanine to tyrosine remained un-

changed. During TPPN, the concentrations of phenylalanine

increased in both groups but were not significantly different.

Because this amino acid is supplied in the infusion solution, a

rise in the plasma concentration was not unexpected. The TPPN

solution also contained a small amount oftyrosine (10% of the

phenylalanine concentration); however, plasma tyrosine con-

centrations were decreased below the 24-h fasting concentration

during TPPN infusion. This suggests that there was an anabolic

protein response to the amino acid infusion that caused a de-

crease in the tyrosine pool.

As noted above, plasma methionine concentrations have been

shown to be higher after a major operation (1 3), during sepsis(1 1, 12), and after accidental injury (6). A similar response was

noted in the geriatric trauma group in this study. The increasewas comparable to the severely injured geriatric patient group

reported by Jeevanandam (20). Comparison ofour 30% increase

in plasma methionine to his reported 182% increase in a younger

population ofinjured adults suggests an age difference in response

to injury.As with other EAAs, lysine also showed a variable response

to stress. A significantly lower lysine concentration as noted in

the geriatric population reported here is unlike that observed inaccidental trauma in younger groups (10). Askanazi et al (12)

showed comparable plasma concentrations in patients with ac-

cidental injury or during sepsis compared with concentrations

in control subjects. In addition, these investigators showed that

the decreased EAA pool after trauma was correlated with lower

plasma concentrations of all EAAs except lysine. The lower

plasma lysine concentration in the present study may be pre-sumed to reflect increased catabolism. Increased intracellular

concentration and increased breakdown of EAAs is also a man-

ifestation of lower plasma concentrations in trauma.

After trauma, nearly all of the NEAA concentrations, es-

pecially glutamine and glycine, were lower. This response in

geriatric patients is typical for all levels of stress and appears to

be age independent. Glutamine plays an essential role in nitrogen

transport and as an energy source for certain tissues and it ac-

counts for 60% of the total intracellular free amino acid pool

(except taurine) (33). After trauma the depletion of glutamineis the primary reason for the precipitous decline in both muscle

and plasma NEAA concentrations (12).The catabolic response as defined by various indices noted

herein is present in geriatric patients after hip fracture and the

magnitude of the insult may be comparable to a simple long

bone fracture in a younger population. Because a catabolic re-sponse is evident, the question of increased protein and energyrequirements are ofconcern. A positive nitrogen balance in the

control and trauma groups receiving 1.5 g amino acids . kg� .

suggests that this amount is more than adequate for protein

synthesis. The geriatric trauma group was in positive balance-

3.4 (based on 60 kg body wt) compared with 4.9 g/d for thecontrol group. In an effort to assess the quality of the amino

acid solution used, an estimation of limiting amino acids was

determined from the plasma concentrations of each EAA duringboth fasting and TPPN. When the plasma concentration of anEAA during infusion of a mixture of amino acids is below thefasting concentration, the infusion solution is defined as one

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GERIATRIC PLASMA AA CONCENTRATIONS 1141

that contains an inadequate concentration of that amino acid

for optimal protein synthesis. This negative difference divided

by the minimum daily requirement ofthat amino would result

in a negative numerical value. The order ofhimiting amino acids

are ranked according to the calculated numerical value. On the

other hand, amino acids in excess of the requirement in theinfusion should show a positive numerical valve and are not

limiting. Because the geriatric trauma patients were in positivenitrogen balance, little can be said about the potential for a lim-iting amino acid with the prescribed intake. It was of interest toknow the relative position ofeach EAA on this basis. The ratiosshown in Table 7 are all positive as anticipated; however, both

the control and trauma groups present the same rank order withleucine being the least positive. a

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