THE MALNOURISHEDPATIENT: NUTRITIONAL

ASSESSMENT ANDMANAGEMENT

Samuel Klein and Khursheed N. Jeejeebhoy

Ingestion and absorption of a nutritionally adequate diet isnecessary to maintain normal body composition and func-tion. Gastrointestinal (GI) diseases can cause malnutrition byaffecting nutrient intake, nutrient absorption, or nutrient re-quirements . Therefore, it is important for gastroenterologiststo understand the principles involved in evaluating and treat-ing malnourished patients .

BASIC NUTRITIONAL CONCEPTS

Energy Stores

Endogenous energy stores are continuously oxidized for fuel .Triglyceride present in adipose tissue is the major fuel re-serve in the body and is critical for survival during periodsof starvation (Table 15-1) . The high energy density andhydrophobic nature of triglycerides make it a fivefold betterfuel per unit mass than glycogen . Triglycerides liberate 9 .3kcal/g when oxidized and are compactly stored as an oilinside the fat cell, accounting for 85% of adipocyte weight .In comparison, glycogen produces only 4 .1 kcal/g on oxida-tion and is stored intracellularly as a gel, containing approxi-mately 2 g of water for every gram of glycogen . Adiposetissue is unable to provide fuel for certain tissues, such asbone marrow, erythrocytes, leukocytes, renal medulla, eyetissues, and peripheral nerves, which cannot oxidize lipidsand require glucose for their energy supply . During endur-ance exercise, glycogen and triglycerides present withinmuscle tissue provide an important source of fuel for work-ing muscles .'

Energy Metabolism

Energy is continuously required for normal organ function,maintenance of metabolic homeostasis, heat production, andperformance of mechanical work. Total daily energy expend-iture (TEE) is composed of resting energy expenditure (nor-mally -70% of TEE), thermic effect of feeding (normally-10% of TEE), and energy expenditure of physical activity(normally -20% of TEE) .

Resting Energy Expenditure

Resting energy expenditure (REE) represents postabsorptiveenergy expenditure while a person lies quietly awake . Dur-ing these conditions, approximately I kcal/kg body weight isconsumed per hour in healthy adults . The energy require-ments of specific tissues differ dramatically (Table 15-2) .The liver, gut, brain, kidneys, and heart constitute approxi-mately 10% of total body weight but account for approxi-mately 75% of the REE . In contrast, resting skeletal muscleconsumes approximately 20% of REE but represents approx-imately 40% of body weight, and adipose tissue consumesless than 5% of REE but usually accounts for more than20% of body weight .

Several equations have been generated to estimate restingenergy requirements 2-5 (Table 15-3). The equations forhealthy subjects generate values that are usually within 10%of measured values . However, these equations are much lessaccurate in persons who are at extremes in weight (eithervery lean or obese) or who are ill because alterations inbody composition and metabolic stress influence energy ex-

265

BASIC NUTRITIONAL CONCEPTS, 265 MALNUTRITION, 271 Refeeding Syndrome, 277Energy Stores, 265 Specific Nutrient Deficiencies, 271 Clinical Recommendations, 278Energy Metabolism, 265 Protein-Energy Malnutrition, 272 PATIENTS WITH SEVERE MALABSORP-Protein, 266 Effect of Protein-Energy Malnutrition on TION, 279

Carbohydrate, 268 Tissue Mass and Function, 273 Clinical Considerations, 279

Lipids, 268 Nutritional Assessment Techniques, 274 Treatment, 280

Major Minerals, 268 REFEEDING THE MALNOURISHED PA-TIENT, 277Micronutrients, 268

STARVATION, 271

pir

TIt

fR t OGY

Table 15-1 1 Endogenous Fuel Stores in a Man Weighing

Recommended Energy Intake inos i l z d t e s

penditure. Malnutrition and hypocaloric feeding decreaseREE to values 15% to 20% below those expected for actualbody size, whereas metabolic stress, such as inflammatorydiseases or trauma, often increases energy requirements .However, it is rare for most illnesses to increase REE bymore than 50% of pre-illness values . For example, patientswith Crohn's disease who do not have an infectious compli-cation have normal metabolic rates6 whereas patients withsevere bums may have a 40% increase in REE. 7

Energy Expenditure of Physical Activity

The effect of physical activity on energy expenditure de-pends on the intensity and duration of daily activities .Highly trained athletes can increase their TEE 10- to 20-foldduring athletic events. The activity factors shown in Table15-4, expressed as a multiple of REE, can be used toestimate TEE in active patients . The energy expended duringphysical activity is equal to :

(REE) X (activity factor)X (duration of activity in hours/24 h) .

TEE represents the summation of energy expended duringall daily activities, including rest periods (Table 15-5) .

Thermic Effect of Feeding

Eating or infusing nutrients increases metabolic rate . Dietaryprotein causes the greatest stimulation of metabolic rate,

Table 15-2 1 Resting Energy Requirements of a Man Weighing 70 kg

REE, resting energy expenditure .

followed by carbohydrate and then fat . A meal containing allthese nutrients usually increases metabolic rate by 5% to10% of ingested or infused calories .

We developed a simple method for estimating total dailyenergy requirements in hospitalized patients based on bodymass index (BMI)A (Table 15-6) . In general, energy givenper kilogram body weight is inversely related to BMI .

Protein

Proteins are composed of amino acids, which are nitrogen-containing compounds . Twenty different amino acids arecommonly found in human proteins . Some amino acids (his-tidine, isoleucine, leucine, lysine, methionine, phenylalanine,threonine, tryptophan, valine, and possibly arginine) are con-sidered essential because their carbon skeletons cannot besynthesized by the body. Other amino acids (glycine, ala-nine, serine, cysteine, cystine, tyrosine, glutamine, glutamicacid, asparagine, and aspartic acid) are nonessential becausethey can be made from endogenous precursors or essentialamino acids . In disease states, nonessential amino acids maybecome essential . For example, it has been shown that cyste-ine is essential in patients with cirrhosis 9 because the trans-sulfuration pathway is impaired in these patients .

The body of an average 75-kg male contains approxi-mately 12 kg of protein and 2 kg of nitrogen . In contrast tofat and carbohydrate, there is no storage depot for protein,so excess intake is catabolized and the nitrogen componentis excreted . Inadequate protein intake causes net nitrogenlosses, initially from organs such as the liver and then frommuscle mass. Data from nitrogen balance studies suggestthat the mean daily protein requirement for adults is 0 .6 g/kg(with a standard deviation of 12 .5%). Therefore, a proteinintake of 0 .75 g/kg would meet the requirements of 97% ofthe adult population. However, this amount is based on stud-ies in which a reference protein containing a large propor-tion of essential amino acids was used. Requirements fordietary protein of lesser biologic value may be higher . Intra-venously administered amino acids are as effective in main-taining nitrogen balance as oral protein of the same aminoacid composition . 1 °

Individual protein requirements are affected by several

TISSUE MASS ENERGY CONSUMED

TISSUE GramsPercentage

Body WeightKilocalories/gramof Tissue per Day Kilocalories/Day

PercentageREE

Liver 1550 2 .2 0 .28 445 19Gut 2000 3 .0 0.15 300 13Brain 1400 2 .0 0 .30 420 18Kidneys 300 0 .4 1 .27 360 15Heart 300 0 .4 0.80 235 10Skeletal muscle 28,000 40 .0 0.014 400 18Adipose 15,000 21 .0 0.005 80 4

70 kg

TISSUE

MASS

FUEL SOURCE Grams Kilocalories

Adipose Triglyceride 13,000 120,000Liver Glycogen 100 400

Protein 300 1200Triglyceride 50 450

Muscle Protein 6000 24,000Glycogen 400 1600Triglyceride 250 2250

Blood Glucose 3 12Triglyceride 4 35Free fatty acids 0 .5 5

Table 15-3 1 Commonly Used Formulas for CalculatingResting Metabolic Rate

HARRIS-BENEDICT EQUATIONMen :66+(13.7X W)+(5 X H)-(6.8XA)Women :665+(9.6X W)+(1 .8x H)-(4.7xA)WORLD HEALTH ORGANIZATION

879 + (10.2 X W)Women :795 + (7 .18 X W)IRETON-JONES ET AL.Spontaneously breathing :629 - (11 X A) + (25 X W) - (609 X Q)Ventilator dependent :1925 - (10 X A) + (5 X W) + (281 XG)+(292XT) + (851

THr .1AI vi x R+'I+LP PATttN I . W4ty lru

t ?t tt,

X B)

A, age in years ; B, diagnosis of burn (present = 1, absent = 0) ; G, gender(male = 1, female = 0); H, height in centimeters ; 0, obesity (present = 1, absent= 0) ; T, diagnosis of traumas (present = 1, absent = 0) ; W, weight in kilograms .

factors, such as the amount of nonprotein calories provided,overall energy requirements, protein quality, and the pa-tient's nutritional status (Table 15-7) . Protein requirementsincrease when calorie intake does not meet energy needs .The magnitude of this increase is directly proportional to thedecrease in energy supply . Conversely, at any level of sub-optimal protein intake, nitrogen balance can be improved byincreasing energy intake. Therefore, nitrogen balance reflectsboth protein intake and energy balance . Fasting animals andhumans excrete nitrogen at rates that are proportional totheir metabolic rates and is estimated to be approximately 2mg N/kcal of REE.t t Illness, by increasing catabolism andmetabolic rate, also increases requirements for protein (seeTable 15-7) . Protein requirements are also determined bythe availability of adequate amounts of essential amino acidsin the protein source. Inadequate amounts of any of theessential amino acids result in inefficient utilization . In gen-eral, approximately 15% to 20% of total protein require-

Table 15-5 1 Daily Energy Requirements in Humans

REE, resting energy expenditure; TEE, total daily energy expenditure .

ments should be in the form of essential amino acids innormal adults .

Nitrogen Balance

Nitrogen balance is calculated as the difference between ni-trogen intake, in the form of amino acids or protein, andnitrogen losses in urine, stool, skin, and body fluids . Nitro-gen balance can be used to estimate protein balance becauseapproximately 16% of protein consists of nitrogen and it isassumed that all body nitrogen is incorporated into protein .A positive balance (intake greater than losses) representsanabolic conditions and a net increase in total body protein,whereas a negative balance demonstrates net protein catabo-lism. For example, a negative nitrogen balance of 1 g/dayrepresents a 6 .25 g/day (16% of 6.25 g protein = 1 gnitrogen) loss of body protein, which is equivalent to a 30 g/day loss of hydrated lean tissue . In practice, nitrogen balancestudies tend to be artificially positive because of overestima-tion of dietary nitrogen intake and underestimation of lossescaused by incomplete urine collections and unmeasured out-puts .

It is important to consider the patient's recent proteinintake and nutritional status in interpreting nitrogen balancedata. When a person ingesting a low-protein diet is re-fedprotein, nitrogen excretion does not rise proportionately tointake and there is retention of administered nitrogen . This

Age (Years)0-3

Male(60 .9 X W) - 54

Female(61 .0X W) - 51

3-10 (22 .7 X W) - 495 (22.5 x W) + 49910-18 (17.5 X W) + 651 (12.2 X W) + 74618-30 (15 .3 X W) + 679 (14.7 x W) + 99630-60 (11 .2 X W) + 879 (8.7 x W) + 829>60 (13.5 X W) + 987 (10.5 x W) + 596

OWEN ET AL .Men :

Table 15-4 1 Factors Used to Estimate Thermic Effectof Physical Activity

Table 15-6 1 Estimated Energy Requirementsfor Hospitalized Patients Based on BodyMass Index

ACTIVITY ACTIVITYLEVEL EXAMPLES FACTOR BMI (kg/m 2)

ENERGY REQUIREMENTS (kcal/kg/day)*

<15

35-40Resting 1 .0

15-19

30-35Very light Standing, driving, typing 1 .1-2 .0Light Walking 2-3 mph, shopping, light 2.1-4 .0 20-29

20-25

housekeeping?30

15-20

Moderate Walking 3-4 mph, biking, gardening, 4.1-6 .0

Heavyscrubbing floors

Running, swimming, climbing, bas-ketbal I

6.1-10 .0

*These values are recommended for critically ill patients and all obese pa-tients ; add 20% of total calories in estimating energy requirements in non-criti-cally ill patients .

BMI, body mass index .The lower range within each BMI category should be considered in insulin-

resistant or critically ill patients to decrease the risk of hyperglycemia and infec-tion associated with overfeeding .

Adapted from Alpers DA, Stenson WE, Bier DM . Manual of Nutritional Thera-peutics . Boston : Little, Brown, 1995 .

AGE (Yr)REE

(kcal/kg)ACTIVITYFACTOR

TEE(kcal/kg)

Male11-14 32 .0 1 .70 5515-18 26 .7 1 .67 4519-25 24 .7 1 .67 4025-50 22.8 1 .60 37>51 19 .8 1 .50 30

Female11-14 28 .5 1 .67 4715-18 24 .9 1 .60 4019-24 23 .2 1 .60 3825-50 21 .9 1 .55 36>51 19 .7 1 .50 30

PROTEIN REQUIREMENTSCLINICAL CONDITION

(g/kg IBW/day)

.t3Sf :"TK0FIsi7t~RC'3L[XA'

IBW, ideal body weight .Additional protein requirements are needed to compensate for excess protein

loss in specific patient populations, such as patients with burn injuries, openwounds, and protein-losing enteropathy or nephropathy . Lower protein intake maybe necessary in patients with chronic renal insufficiency not treated by dialysisand certain patients with liver disease and hepatic encephalopathy .

gain during early refeeding is caused by a rapid accumula-tion of nitrogen in the liver and, to a lesser extent, inkidneys and muscle . However, the early retention of nitrogenis not sustained and decreases markedly within 4 to 7 days .In contrast, when a person ingesting a high-protein diet de-creases protein intake, the previously high urinary nitrogenloss continues for a few days despite the reduced intake,resulting in a negative nitrogen balance . Similarly, initialnitrogen loss after injury is greater in well-nourished than inmalnourished patients . Therefore, a "labile" nitrogen pool ofapproximately 60 g contributes to short-term alterations innitrogen balance and makes short-term nitrogen balancemeasurements an unreliable method for determining optimalprotein intake .

Carbohydrate

Approximately 400 g of digestible carbohydrates are eateneach day in a normal diet : 60% as starch (polysaccharidemade from maize, rice, wheat, and potato) ; 30% as sucrose(disaccharide made from sugar cane and beet sugar) ; and10% as lactose (disaccharide made from milk). In addition,approximately 10 to 20 g of indigestible carbohydrate (solu-ble and insoluble fibers) are consumed daily . Complete di-gestion of the principal dietary carbohydrates generatemonosaccharides (glucose, fructose, and galactose) . All cellsare able to generate energy (adenosine triphosphate) by me-tabolizing glucose to either three-carbon compounds via gly-colysis or to carbon dioxide and water via glycolysis and thetricarboxylic acid cycle .

There is no dietary requirement for carbohydrate becauseglucose can be synthesized from endogenous amino acidsand glycerol. Nevertheless, carbohydrate is an important fuelbecause of the interactions between carbohydrate and proteinmetabolism. Carbohydrate intake stimulates insulin secretion,which inhibits muscle protein breakdown,' 2 stimulates mus-cle protein synthesis, 13 and decreases endogenous glucoseproduction from amino acids . 14 In addition, glucose is therequired or preferred fuel for red and white blood cells, therenal medulla, eye tissues, peripheral nerves, and the brain .However, once glucose requirements for these tissues (-150g/day) are met, the protein-sparing effects of carbohydrateand fat are similar. 15, 16

Lipids

Lipids consist of triglycerides (fat), sterols, and phospholip-ids. These compounds serve as sources of energy ; precursors

for steroid hormone, prostaglandin, thromboxane, and leuko-etriene synthesis ; structural components of cell membranes'and carriers of essential nutrients . Dietary lipids are com-posed mainly of triglycerides, which contain saturated andunsaturated long-chain fatty acids of 16 to 18 carbon chainsin length. The use of fat as a fuel requires the hydrolysis oendogenous or exogenous triglycerides and cellular uptake ofreleased fatty acids . Long-chain fatty acids are deliveredacross the outer and inner mitochondrial membranes by acarnitine-dependent transport system ." Once inside the mito-chondria, fatty acids are degraded by beta oxidation to acetylcoenzyme A (CoA), which then enters the tricarboxylicacid cycle . Therefore, the ability to use fat as a fuel de-pends on normal functioning mitochondria . A decrease inthe number of mitochondria or oxidative enzymes, associatedwith aging or deconditioning, favors the use of carbohydrateas a fuel ."

Essential Fatty Acids

Most fatty acids can be synthesized by the liver, but humanslack the desaturase enzyme needed to produce the n-3 (dou-ble bond between carbons 3 and 4 counted from the methylend) and n-6 (double bond between carbons 6 and 7) fattyacid series. Linoleic acid (C18 :2, n-6) should constitute aleast 2% and linolenic acid (C18 :3, n-6,9,12) at least 0 .5%of the daily caloric intake to prevent the occurrence of es-sential fatty acid deficiency (EFAD) . Before the advent ofparenteral nutrition, a clinical syndrome of EFAD, mani-fested as a rash and a specific alteration in the plasma fattyacid profile, was recognized only in infants . Adults did notseem to demonstrate this syndrome because of sufficientessential fatty acids stores in adipose tissue . The use oftotal parenteral nutrition given as a continuous infusionof a fat-free hypertonic glucose solution led to EFAD inadults, and the plasma pattern of EFAD was observed asearly as 10 days after glucose-based total parenteralnutrition was started, before the onset of any clinicallyobservable features . 19 The increase in plasma insulin con-centrations caused by total parenteral nutrition is presum-ably responsible for EFAD because insulin inhibits lipoly-sis and, therefore, the release of endogenous essential fattyacids .

Major Minerals

Major minerals are inorganic nutrients that are required inlarge (>100 mg/day) quantities and are important for ionicequilibrium, water balance, and normal cell function . Malnu-trition and nutritional repletion can have dramatic effects onmajor mineral balance . Evaluation of macromineral defi-ciency and recommended dietary intake for healthy adultsare shown in Table 15-8 .

Micronutrients

Micronutrients consist of trace elements and vitamins . Bothforms of micronutrients are essential because, as constituents

Normal 0.75Metabolic stress 1 .0-1 .5Hemodialysis 1 .2-1 .4Peritoneal dialysis 1 .3-1 .5

THE MAINOUKISH S) PA rl ' t Nli 1s tttc)NAl. Mse5iaaetvf'

Table 15-8 ~ Major Mineral Requirements and Assessment of Deficiency

LABORATORY EVALUATION

of enzyme complexes, they regulate metabolic processes and

requirements that are considerably higher than the recom-substrate metabolism . The recommended dietary intake for

mended dietary intake .trace elements and vitamins (Tables 15-9 and 15-10) is setat two standard deviations above the estimated mean so thatit covers the needs of 97% of the healthy population . There-

Trace Elementsfore, the recommended dietary intake exceeds the micronu-trient requirements of most persons . However, patients with Trace minerals are inorganic nutrients that are required indisease, particularly those who have decreased GI absorptive small (<100 mg/day) quantities (see Table 15-9) . Fifteenfunction and increased micronutrient GI losses, may have

elements have been found to be essential for health in

Table 15-9 J Trace Mineral Requirements and Assessment of Deficiency

*Recent evidence suggests that manganese toxicity, manifested as extrapyramidal and parkinsonian-like symptoms, can occur in patients with chronic liver disease orthose receiving long-term parenteral nutrition . Many clinicians now limit manganese addition to parenteral nutrition solutions to < 0 .1 mg/d or eliminate it entirely (seereference 21 ) .

LABORATORY EVALUATION

MINERAL ENTERAL PARENTERALSYMPTOMS OR SIGNS

OF DEFICIENCY Comment

Chromium 30-200 Ag 10-20 Ag Glucose intolerance, periph- Serum Does not reflect body stores

Copper 2 mg 0.3 mg

eral neuropathy, encepha-lopathy

Anemia, neutropenia, osteo-Glucose tolerance testSerum copper

Not specificInsensitive for body stores

Iodine 150 ug 70-140 ug

porosis, diarrhea

Hypothyroidism, goiterPlasma ceruloplasminUrine iodine

Acute phase reactantReflects recent intake

Iron 10-15 mg 1-1 .5 mg Microcytic hypochromicThyroid stimulating hormoneSerum iron and total iron

Reflects thyroid functionPoor measure of body stores;

Manganese 1 .5 mg 0.2-0.8 mg*

anemia

Hypercholesterolemia, de-

binding capacity

Serum manganese

high specificity when lev-els low; poor sensitivity

Does not reflect body stores

Selenium 55 ag 20-40 sgmentia, dermatitis

Cardiomyopathy (Keshan's Serum selenium Insensitivity for body stores

Zinc 15 mg 2 .5-4 mg

disease), muscle weakness

Growth retardation, delayed

Blood glutathione peroxidaseactivity

Plasma zinc

More sensitive for bodystores

Poor specificity for bodysexual maturation, hypo-gonadism, alopecia, acro-orificial skin lesion, diar-rhea, mental statuschanges

stores

MINERAL ENTERAL PARENTERALSYMPTOMS OR SIGNS

OF DEFICIENCY Comment

Sodium 0.5-5 g 60-150 mmol Hypovolemia, weakness Urinary sodium May not reflect body stores ;clinical evaluation is best

Potassium 2-5 g 60-100 mmol Weakness, paresthesias, ar-rhythmias

Serum potassium May not reflect body stores

Magnesium 300-400 mg 5-15 mmol Weakness, twitching, let-any, arrhythmias, hypo-calcemia

Serum magnesium

Urinary magnesium

May not represent body stores

May not represent body storesCalcium 800-1200 mg 5-15 mmol Osteomalacia, tetany, ar-

rhythmias24-hr urinary calcium

Dual energy x-ray absorp-tiometry

Reflects recent intake

Reflects bone calcium content

Phosphorus 800-1200 mg 20-60 mmol Weakness, fatigue, leuko-cyte and platelet dys-function, hemolytic ane-mia, cardiac failure, anddecreased oxygenation

Plasma phosphorus May not reflect body stores

Table 15-10 1 Vitamin Requirements and Assessment of Deficiency

RBC, red blood cell .

animals : iron, zinc, copper, chromium, selenium, iodine,cobalt, manganese, nickel, molybdenum, fluorine, tin, sili-con, vanadium, and arsenic . However, according to thestrict criteria suggested by Cotzias, 20 only the first sevenhave been shown to be necessary for health in humans .Recent data suggest that the recommended daily parenteralintake for manganese may be too high in patients withchronic liver disease or those receiving long-term parenteralnutrition because of excessive manganese deposition in basalganglia, causing extrapyramidal and Parkinson-like symp-toms .21

C (ascorbic acid)

75-90 mg

100 mg

Scurvy, petechia, purpura,(125 mg

gingival inflammation andin smokers)

bleeding, weakness, de-pression

Vitamins

Vitamins are organic compounds that are required in small(<100 mg/day) quantities (see Table 15-10). A negativebalance between vitamin intake and vitamin utilization pluslosses causes clinical symptoms of vitamin deficiency . Theamount of time before the onset of clinical manifestationsdepends on the cumulative negative vitamin balance and thesize of available vitamin stores . In general, water-solublevitamin body stores are much smaller than fat-soluble vita-min stores, and so the onset of symptoms is more rapid for

LABORATORY EVALUATION

Serum methylmalonicacid

Plasma ascorbic acid

Comment

Not specific for vita-min 1

Reflects body stores

Reflects body stores

Reflects recent intake

Reflects recent intake

Reflects body stores

Reflects body storesand recent intake

Reflects body storesReflects body stores

Tests functional blockin enzyme

Reflects recent intake

Leukocyte ascorbic

Reflects recent storesacid

VITAMIN ENTERAL PARENTERALSYMPTOMS OR SIGNS

OF DEFICIENCY Test

A (retinol) 5000 IU 3300 IU Night blindness, Bitot's spots, Serum retinal

D (ergocalciferol) 400 IU 200 IU

keratomalacia, follicularhyperkeratosis, xerosis

Rickets, osteomalacia, osteo- Serum 25-hydroxyvi-

E (alpha-tocopherol) 33 IU 33 IU

porosis, bone pain, muscleweakness, tetany

Hemolysis, retinopathy, neu-

tamin D

Serum tocopherol

K (phylloquinone) 50-100 µg 100 µg

ropathy

Easy bruising and bleeding,

Serum tocopherol : to-tal lipid ratio

Prothrombin time

B, (thiamine)

B 2 (riboflavin)

1-1 .5 mg

1 .1-1 .8 mg

3 mg

3 .6 mg

abnormal clottingBeriberi, cardiac failure,

Wernicke's encephalopa-thy, peripheral neuropathy,fatigue, ophthalmoplegia

Cheilosis, sore tongue and

RBC transketolase ac-tivity

RBC glutathione re-

B 3 (niacin) 12-20 mg 40 mg

mouth, eye irritation, seb-horrheic dermatitis

Pellagra (dermatitis, diarrhea,

ductase activity

Urinary N-methyl-nic-

B 5 (pantothenic acid) 5-10 mg 10 mg

dementia), sore mouth andtongue

Fatigue, weakness, paresthe-

otinamide

Urinary pantothenic

B6 (pyridoxine)

B 7 (biotin)

1-2 mg

100-200 µg

4 mg

60 µg

sias, tenderness of heelsand feet

Sebhorrheic dermatitis, chei-losis, glossitis, peripheralneuritis, convulsions, hy-pochromic anemia

Sebhorrheic dermatitis, alope-

acid

Plasma pyridoxalphosphate

Plasma biotin

B9 (folic acid) 400 µg 400 µg

cia, change in mentalstatus, seizures, myalgia,hyperesthesia

Megaloblastic anemia, glossi- Serum folic acid

B 12 (cobalamin) 3 µg 5 µg

tis, diarrhea

Megaloblastic anemia, pares-RBC folic acidSerum cobalamin

thesias, decreased vibratoryor position sense, ataxia,mental status changes, diar-rhea

water-soluble than for fat-soluble vitamin deficiency . Bloodtest results usually become abnormal before the onset ofclinical manifestations and can be used to assess the needfor supplementation (see Table 15-10) .

STARVATION

During starvation, a complex and carefully integrated seriesof metabolic alterations decrease metabolic rate, maintainglucose homeostasis, conserve body nitrogen, and increasethe use of adipose tissue triglycerides to meet energy needs .During the first 24 hours of fasting, hepatic glucose produc-tion and oxidation decrease, whereas whole-body lipolysisand ketone body production increase .22 The relative contribu-tion of gluconeogenesis to hepatic glucose production in-creases as the rate of hepatic glycogenolysis declines ; at 24hours of fasting, only 15% of liver glycogen stores remain . 23Glucose is oxidized predominantly by the brain and glucose-requiring tissues, accounting for approximately 20% of totalenergy consumption . The oxidation of fatty acids releasedfrom adipose tissue triglycerides accounts for approximately65% of energy consumed during the first 24 hours of fast-ing. Approximately 15% of resting energy requirements isprovided by the oxidation of protein; 70 g of amino acidsare mobilized from protein stores, and 10 g of nitrogen areexcreted in urine . 24

During short-term starvation (1-14 days of fasting), thedecline in plasma insulin, increase in plasma epinephrine,and increase in lipolytic sensitivity to catecholamines stimu-late adipose tissue lipolysis 25 . 26 The increase in fatty aciddelivery to the liver, in conjunction with an increase in theratio of plasma glucagon :insulin concentration, enhances theproduction of ketone bodies by the liver . 27 A maximal rateof ketogenesis is reached by 3 days of starvation, andplasma ketone body concentration is increased 75-fold by 7days. In contrast to fatty acids, ketone bodies can cross theblood-brain barrier and provide most of the brain's energyneeds by 7 days of starvation . 28 The use of ketone bodies bythe brain greatly diminishes glucose requirements and thusspares the need for muscle protein degradation to provideglucose precursors. If early protein breakdown rates were tocontinue throughout starvation, a potentially lethal amount ofmuscle protein would be catabolized in less than 3 weeks .Whole-body glucose production decreases by more than halfduring the first few days of fasting because of a markedreduction in hepatic glucose output . As fasting continues, theconversion of glutamine to glucose in the kidney representsalmost 50% of total glucose production . Energy is conservedby a decrease in physical activity caused by fatigue and areduction in REE caused by increased conversion of activethyroid hormone to its inactive form, 29 and suppressed sym-pathetic nervous system activity . 30

During long-term starvation (14-60 days of fasting),maximal adaptation is reflected in a plateau in lipid, carbo-hydrate, and protein metabolism . The body relies almostentirely on adipose tissue for its fuel, which provides morethan 90% of daily energy requirements . Muscle proteinbreakdown decreases to less than 30 g/day, causing amarked decrease in urea nitrogen production and excretion .The decrease in osmotic load diminishes urine volume to200 mL/day, thereby limiting fluid requirements. Total glu-

THE MALNCLJRL"H[1) PAn NT : NUTRITION A[ AS

core production decreases to approximately 75 g/day, pro-viding fuel for glycolytic tissues (40 g/day) and the brain(35 g/day) while maintaining constant plasma glucose con-centration. Energy expenditure decreases by 20% to 25% at30 days of fasting 31 and remains relatively constant thereaf-ter despite continued starvation .

The metabolic response to short-term and long-term star-vation differs between lean and obese persons . Obesity isassociated with a blunted increase in lipolysis and decreasein glucose production compared with that in lean persons .32, 33In addition, protein breakdown and nitrogen losses are lessin obese than lean persons, thereby helping conserve muscleprotein. 34

The events that mark the terminal phase of starvationhave been studied extensively in rats . Body fat mass, muscleprotein, and the sizes of most organs are markedly de-creased . The weight and protein content of the brain, how-ever, remain relatively stable throughout starvation . Duringthis final phase of starvation, body fat stores reach a criticallevel, energy derived from body fat decreases, and muscleprotein catabolism is accelerated . Death commonly occurswhen there is a 30% loss of muscle protein . 35 The mecha-nisms responsible for death from starvation in humans arenot well understood . In general, the duration of survivalduring starvation depends on the amount of available bodyfuels and lean body mass . The possibility that there arelethal levels of body weight loss (loss of 40% of bodyweight), 36 of protein depletion (loss of 30%-50% of bodyprotein),37 of fat depletion (loss of 70%-95% of body fatstores)," or of body size (body mass index of 13 for menand 11 for women) 39 has been proposed . In normal-weightmen, death occurs after approximately 2 months of starva-tion, when more than 35% (-25 kg) of body weight islost. 38 In contrast, obese persons have undergone therapeuticfasts for more than a year without adverse consequences .The longest reported fast was that of a 207 kg man whoingested acaloric fluids, vitamins, and minerals for 382 daysand lost 61% (126 kg) of his initial weight . 40

MALNUTRITION

A normal nutritional status represents a healthy balance be-tween nutrient intake and nutrient requirements. Malnutritionrepresents a continuum of events caused by nutrient disequi-librium, which alters intermediary metabolism, organ func-tion, and finally body composition . Therefore, in a generalsense, malnutrition can be defined as any metabolic, func-tional, or compositional alteration caused by inadequate nu-trient intake. Malnutrition can be caused by specific nutrientdeficiencies and a more generalized deficiency in protein andenergy .

Specific Nutrient Deficiencies

A careful history and physical examination, routine bloodtests, and selected laboratory tests can be used to diagnosespecific macronutrient, major mineral, vitamin, and tracemineral deficiencies (see Tables 15-8 to 15-11) . Replace-ment of the deficient nutrient usually corrects the biochemi-

Table 15-11 1 Selected Symptoms and Signsof Nutritional Deficiencies

NCHS, National Center for Health Statistics .

cal and physical abnormalities but may not cure the underly-ing cause of the problem. For example, iron therapy correctsiron deficiency anemia but not the factors responsible for thedeficiency (e .g ., inadequate intake, malabsorption, or ironloss) .

Protein-Energy Malnutrition

The term protein-energy malnutrition (PEM) has been usedto describe several nutritional deficiency syndromes, includ-ing kwashiorkor, marasmus, and nutritional dwarfism in chil-dren, and wasting associated with illness or injury in chil-dren and adults . Primary PEM is caused by inadequatenutrient intake, so the functional and structural abnormalitiesassociated with primary PEM are often reversible with nutri-

Table 15-12 1 Waterlow Classification of Protein-Energy Malnutrition in Children

PARAMETER

NORMAL

tional therapy. However, prolonged primary PEM can causeirreversible changes in organ function and growth . Second-ary PEM is caused by illness or injury, which alter appetite,digestion, absorption, or nutrient metabolism . Wasting disor-ders, such as cancer, acquired immunodeficiency syndrome,and rheumatologic diseases, are characterized by involuntaryloss of body weight and muscle mass in the setting of achronic illness. These patients often experience wasting be-cause of 1) inadequate nutrient intake caused by anorexiaand possibly gastrointestinal tract dysfunction, and 2) meta-bolic abnormalities caused by alterations in regulatory hor-mones and cytokines . Alterations in metabolism causegreater loss of muscle tissue than that observed with purestarvation or semi-starvation . Restoration of muscle mass isunlikely with nutrition support unless the underlying inflam-matory disease is corrected . Most of the weight that isgained after providing nutrition support is due to increasesin fat mass and body water without significant increases inlean tissue.

Protein-Energy Malnutrition in Children

Undernutrition in children differs from that in adults becauseit affects growth and development. Much of our understand-ing of undernutrition in children comes from observationsmade in underdeveloped nations where poverty, inadequatefood supply, and unsanitary conditions lead to a high preva-lence of PEM. The Waterlow classification of malnutritiontakes into account a child's weight-for-height (wasting) andheight-for-age (stunting)" (Table 15-12) . The characteristicsof the three major clinical syndromes of PEM in children,kwashiorkor, marasmus, and nutritional dwarfism, are out-lined in Table 15-13 .42 Although these three syndromes areclassified separately, they may coexist in the same patient .

Marasmus

Weight loss and marked depletion of subcutaneous fat andmuscle mass are characteristic features of children with ma-rasmus . Loss of fat and muscle make ribs, joints, and facialbones prominent . The skin is thin, loose, and lies in folds .

Kwashiorkor

The word "kwashiorkor" comes from the Ga language ofWest Africa and can be translated as "disease of the dis-placed child" because it was commonly seen after weaning .The presence of peripheral edema distinguishes children with

Weight-for-height (wasting)Percent of median NCHS standard 90-110 80-89 70-79 <70Standard deviation from the NCHS median +Z to -Z -1 .1 Z to -2 Z -2.1 Z to -3 Z <-3 Z

Height-for-age (stunting)Percent of median NCHS standard 95-105 90-94 85-89 <85Standard deviation from the NCHS median +Z to -Z -1 .1 Z to -2 Z -2.1 Z to -3 Z <-3 Z

ORGANSYSTEM

SYMPTOMS ORSIGNS

POSSIBLE NUTRIENTDEFICIENCY

Skin Pallor Iron, folate, vitamin B 72Follicular hyperkera- Vitamins A and C

tosisPerifollicular petechiae Vitamin CDermatitis Zinc, vitamin A, niacin, ri-

boflavin, essential fattyacids

Bruising, purpura Vitamins C and KHair Easily plucked, alopecia Protein, zinc, biotin

Corkscrew hairs, coiled Vitamins A and Chair

Eyes Night blindness, kerato- Vitamin Amalacia, photophobia

Conjunctival inflamma- Vitamin A and riboflavintion

Mouth Glossitis Riboflavin, niacin, folate,vitamin B 12

Bleeding or receding Vitamins A, C, and K; fo-gums, mouth ulcers late

Burning or sore mouth/ Vitamins B 12 and C ; folate,tongue niacin

Angular stomatitis or Riboflavin, niacin, pyri-cheilosis doxin, iron

Tetany Calcium, magnesiumNeurologic Paresthesias Thiamine, pyridoxine

Loss of reflexes, wrist Vitamins B 12 and Edrop, foot drop, lossof vibratory and posi-tion sense

Dementia, disorienta- Niacin, vitamin B 12tion

Ophthalmoplegia Thiamine

Table 15-13 1 Features of Protein-Energy MalnutritionSyndromes in Children

kwashiorkor from those with marasmus and nutritional dwarf-ism. Children with kwashiorkor also have typical skin andhair changes (see sections on hair and skin changes below) .The abdomen is protuberant because of weakened abdominalmuscles, intestinal distension and hepatomegaly, but there isnever ascites . In fact, the presence of ascites should promptthe clinician to search for liver disease or peritonitis . Chil-dren with kwashiorkor are typically lethargic and apatheticwhen left alone but become very irritable when held .Kwashiorkor is not caused by a relative deficiency in proteinintake and, in fact, protein and energy intake are similar inchildren with kwashiorkor and marasmus . Kwashiorkor oc-curs when there is physiologic stress, such as an infection,in an already malnourished child. This explains why kwashi-orkor is an acute illness compared with the chronicity ofundernutrition alone and why there is overlap between ma-rasmus and kwashiorkor. Kwashiorkor is characterized byleaky cell membranes, which permit the movement of potas-sium and other intracellular ions into the extracellular space .The increased osmotic load in the interstitium causes watermovement and edema.

Nutritional Dwarfism

The child with failure to thrive may be of normal weight forheight but has short stature and delayed sexual development .Providing appropriate feeding can stimulate catch-up growthand sexual maturation .

The diagnosis of PEM is different in adults than in chil-dren because adults do not grow in height. Therefore, under-nutrition in adults causes wasting rather than stunting . Inaddition, although kwashiorkor and marasmus can occur inadults, most studies of adult PEM evaluated hospitalizedpatients who had secondary PEM and coexisting illness orinjury .

Effect of Protein-Energy Malnutrition onTissue Mass and Function

Body Composition

Although all body tissue masses are affected by undemutri-tion, the greatest depletion occurs in fat and muscle masses .Many patients who are malnourished also have intravascular

THE MAI Nt I RIi A- EO P, T,rr T : Nu rRmoNA A$Sts E r

volume depletion because of inadequate water and sodiumintake, decreased plasma proteins, "leaky" capillaries, and"leaky" cells . However, the percent of body weight that iscomposed of water may be increased because of increasedinterstitial ion content and expansion of interstitial space.Therefore, malnourished patients may have diminished intra-vascular volume in the presence of whole-body fluid over-load .

Gastrointestinal Tract

Starvation and malnutrition cause structural and functionaldeterioration of the intestinal tract, pancreas, and liver . Thetotal mass and protein content of the intestinal mucosa andpancreas are markedly reduced . Mucosal epithelial cell pro-liferation rates decrease and the intestinal mucosa becomesatrophic with flattened villi . The synthesis of mucosal andpancreatic digestive enzyme is reduced . Intestinal transportand absorption of free amino acids are impaired, whereashydrolysis and absorption of peptides are maintained . Theabdomen may become protuberant because of hypomotilityand gas distension .

Skin

The skin regenerates rapidly and it takes only 2 weeks for abasal cell of the dermis to reach the cornified layer and die .Undernutrition often causes dry, thin, and wrinkled skin withatrophy of the basal layers of the epidermis and hyperkerato-sis . Severe malnutrition may cause considerable depletion ofskin protein and collagen . Patients with kwashiorkor experi-ence sequential skin changes in different locations . Hyper-pigmentation occurs first, followed by cracking and strippingof superficial layers, thereby leaving behind hypopigmented,thin, and atrophic epidermis that is friable and easily macer-ated .

Hair

Scalp hair becomes thin, sparse, and is easily pulled out. Incontrast, the eyelashes become long and luxuriant and theremay be excessive lanugo hair in children. Children withkwashiorkor experience hypopigmentation with reddish-brown, gray, or blond discoloration . Adults may lose axillaryand pubic hair .

Heart

Chronic undernutrition affects cardiac mass and function .Cardiac muscle mass decreases and is accompanied by frag-mentation of myofibrils . Bradycardia (heart rate can decreaseto less than 40 beats/min) and decreased stroke volume cancause a marked decrease in cardiac output and low bloodpressure .

Lungs

Respiratory muscle function is altered by malnutrition, asevidenced by a decrease in vital capacity, tidal volume, andminute ventilation .

PARAMETER KWASHIORKOR MARASMUS

NUTRI-TIONAL

DWARFISM

Weight for age 60-80 <60 <60(% expected)

Weight for Normal or Markedly Normalheight decreased decreased

Edema Present Absent AbsentMood Irritable when Alert Alert

picked up,apatheticwhen alone

Appetite Poor Good Good

Kidneys

Renal mass and function are often well preserved duringundernutrition, provided adequate water is consumed to pre-vent a severe decrease in renal perfusion and acute renalfailure. However, when malnutrition is severe, there is adecrease in kidney weight, glomerular filtration rate, theability to excrete acid, the ability to excrete sodium, and toconcentrate urine. Mild proteinuria may also occur .

Bone Marrow

Severe undernutrition suppresses bone marrow red blood celland white blood cell production, leading to anemia, leuko-penia, and lymphocytopenia.

Muscle

Muscle function is impaired by malnutrition because of botha loss of muscle mass and impaired metabolism . Decreasedsodium pump activity causes an increase in intracellular so-dium and a decrease in intracellular potassium, which affectsmyocyte electrical potential and contributes to fatigue .

Immune System

Severe undernutrition causes atrophy of all lymphoid tissues,including thymus, tonsils, and lymph nodes. Cell-mediatedimmunity is diminished more than antibody production . Al-terations in cell-mediated immunity cause impaired delayedcutaneous hypersensitivity and anergy . The ability to killbacteria is diminished because of decreased complement andimpaired neutrophil function . Gastrointestinal IgA secretionis also decreased. Malnourished patients are at increased riskfor opportunistic infections and should be considered immu-nocompromised .

Brain

The weight and protein content of the brain remain relativelystable during prolonged malnutrition . Therefore, the integrityof the brain is preserved at the expense of other organs andtissues .

Nutritional Assessment Techniques

The current methods that are used clinically to evaluatePEM in hospitalized adult patients shifts nutritional assess-ment from a diagnostic to a prognostic instrument in anattempt to identify patients who can benefit from nutritionaltherapy. The commonly used indicators of the degree ofprotein-energy malnutrition, detailed below, correlate withclinical outcome . However, these indicators are always influ-enced by illness or injury, making it difficult to distinguishthe contribution of malnutrition from the severity of illnessitself on outcome . Specific features of the medical history,physical examination, and laboratory tests that emphasize theindicators which assess generalized nutritional status includethe following points .

History

The patient or appropriate family members should be inter-viewed to provide insight into the patient's current nutri-tional state and future ability to consume an adequateamount of nutrients . The nutritional history should evaluatethe following issues :

1. Body weight. Has the patient had mild (<5%), moderate(5%-10%), or severe (>10%) unintentional body weightloss in the last 6 months? In general, a 10% or greaterunintentional loss in body weight in the previous 6months is associated with a poor clinical outcome .43, a4

However, it may be difficult to determine true weightloss. Morgan and coworkers45 showed that the accuracyof determining weight loss by history was only 0 .67 andthe predictive power was 0 .75; hence 33% of patientswith weight loss would be missed, and 25% of those whohave been weight-stable would have a diagnosis ofweight loss . Furthermore, the nutritional significance ofchanges in body weight can be confounded by changes inhydration .

2. Food intake . Has there been a change in habitual dietpattern (number, size, and contents of meals)? What isthe reason for altered food intake (e .g ., appetite, mentalstatus or mood, ability to prepare meals, ability to chewor swallow, gastrointestinal symptoms)?

3. Evidence of malabsorption. Does the patient have symp-toms that are consistent with malabsorption?

4. Evidence of specific nutrient deficiencies . Are theresymptoms of specific nutrient deficiencies, including ma-crominerals, micronutrients, and water (see Tables 15-8to 15-11)?

5. Influence of disease on nutrient requirements . Does thepatient's underlying illness increase nutrient needs be-cause of high metabolic stress or nutrient losses?

6. Functional status . Has the patient's ability to function andperform normal daily activities changed?

Physical Examination

The physical examination corroborates and adds to the find-ings obtained by history .

1 . Body mass index (BMI), which is defined as weight (inkilograms) divided by height (in square meters), can helpidentify patients at increased risk of an adverse clinicaloutcome46, 47 (Table 15-14) . Patients who are extremelyunderweight (BMI < 14 kg/m 2) are at high risk of deathand should be considered for admission to the hospitalfor nutrition support.

2. Anthropometry . Triceps and subscapular skinfold thick-nesses provide an index of body fat ; midarm musclecircumference provides a measure of muscle mass . Al-though these measurements seem to be useful in popula-tion studies, their reliability in individual patients is lessclear. The most commonly used standards for tricepsskinfold thickness and midarm muscle circumference arethose reported by Jelliffe, 48 which are based on measure-ments of European male military personnel and low-in-come American women, and those reported by Frisan-cho,49 which are based on measurements of white males

Table 15-14 1 Classification of Nutritional Statusby Body Mass Index in Adults

BODY MASS INDEX(kg/m=)

NUTRITIONAL STATUS

<16.0

Severely malnourished16.0-16.9

Moderately malnourished17 .0-18 .4

Mildly malnourished18.5-24 .9

Normal25.0-29.9

Overweight30.0-34 .9

Obese (class I)35.0-39.9

Obese (class II)?40

Obese (class III)

and females participating in the 1971 to 1974 UnitedStates Health and Nutrition Survey . The use of thesestandards to identify malnutrition in many patients isproblematic because of the restricted database and theabsence of correction factors for age, hydration, andphysical activity on anthropometric parameters . Severalstudies have demonstrated that 20% to 30% of healthycontrol subjects would be considered malnourished on thebasis of these standards and that there is poor correlationbetween Jelliffe's and Frisancho's standards in classifyingpatients .50 51 Furthermore, Hall and associates 52 foundconsiderable inconsistencies when anthropometric mea-surements were performed by different observers .

3. Hydration status. The patient should be evaluated forsigns of dehydration (manifested by hypotension, tachy-cardia, postural changes, mucosal xerosis, decreased axil-lary sweat, and dry skin), and excess body fluid (mani-fested by edema or ascites) .

4. Tissue depletion. A general loss of adipose tissue can bejudged by clearly defined bony, muscular, and venousoutlines and loose skinfolds . A fold of skin, pinchedbetween the forefinger and thumb, can reveal the ade-quacy of subcutaneous fat . The presence of hollowness inthe cheeks, buttocks, and perianal area suggests body fatloss. An examination of the temporalis, deltoid, andquadriceps muscles should be made to search for musclewasting .

5. Muscle function . Strength testing of individual musclegroups should be made to evaluate for generalized andlocalized muscle weakness . In addition, a general evalua-tion of respiratory and cardiac muscle function should bemade .

6. Specific nutrient deficiencies (see Tables 15-8 to 15-11). Rapidly proliferating tissues, such as oral mucosa,hair, skin, and bone marrow are often more sensitive tonutrient deficiencies than are tissues that turn over moreslowly .

Laboratory Tests

Specific Nutrient Deficiencies

Suspected specific nutrient deficiencies based on history andphysical examination can be further corroborated by appro-priate diagnostic laboratory tests (see Tables 15-8 to15-11) .

i -IE AQA!AC>Lf'tSl4EL) PA)7J'T : Nt'rRl15)1

SERUM ALBUMIN. Several studies have demonstrated that alow serum albumin concentration is correlated with an in-creased incidence of medical complications . s3-55 However,an understanding of albumin physiology clarifies why serumalbumin concentration is correlated with disease severity inhospitalized patients, but may be inappropriate as a measureof nutritional status per se. 56 Albumin is highly water-solubleand resides in the extracellular space . The total body pool ofalbumin in a normal 70-kg man is approximately 300 g .Approximately one third of the total pool constitutes theintravascular compartment, and two thirds constitute the ex-travascular compartment.57 The concentration of albumin inblood is greater than that in lymph or other extracellularfluids, but the ratio of intravascular to extravascular albuminconcentration varies from tissue to tissue . Within 30 minutesof initiating albumin synthesis, the hepatocyte secretes albu-min into the bloodstream . 5 S Once albumin is released intoplasma, its half-life is approximately 20 days . During steadystate conditions, approximately 14 g of albumin (200 mg/kg)are produced and degraded daily . Thus, approximately 5%of the total albumin pool is degraded and replaced by newlysynthesized albumin every day . Equilibration of albumin inthe intravascular compartment is rapid and occurs withinminutes after albumin enters the bloodstream . Equilibrationbetween intravascular and extravascular albumin is slower.Every hour approximately 5% of the plasma albumin poolexchanges with extravascular albumin, so that the totalplasma albumin mass exchanges with extravascular albumineach day .

Protein-calorie malnutrition (i .e ., the state of prolongeddeficient intake of protein and calories) causes a decrease inthe rate of albumin synthesis . Within 24 hours of fasting, therate of albumin synthesis decreases markedly . 59 However, ashort-term reduction in albumin synthesis has little impacton albumin levels because of albumin's slow turnover rateand large pool size . Indeed, plasma albumin concentrationmay actually increase during short-term fasting because ofreduction of intravascular water . 60 Even during chronic mal-nutrition, plasma albumin concentration is often maintainedbecause of a compensatory decrease in albumin degradationand a transfer of extravascular albumin to the intravascularcompartment. Prolonged protein-calorie restriction inducedexperimentally in human volunteers 31 or observed clinicallyin patients with anorexia nervosa 61 causes marked reductionsin body weight but little change in plasma albumin concen-tration . A protein-deficient diet with adequate calories inelderly persons causes a decrease in lean body mass andmuscle function without a change in plasma albumin con-centration . 62

Hospitalized patients may have low levels of plasma al-bumin for several reasons . Inflammatory disorders cause adecrease in albumin synthesis,63 an increase in albumin deg-radation, 64 and an increase in albumin transcapillary losses . 65Specific gastrointestinal and cardiac diseases increase albu-min losses through the gut, whereas some renal diseases cancause considerable albuminuria . Wounds, burns, and perito-nitis can cause albumin losses from the injured surface ordamaged tissues. During serious illness, vascular permeabil-ity increases dramatically and alters albumin exchange be-tween intravascular and extravascular compartments . Albu-min losses from plasma to the extravascular space wereincreased twofold in patients with cancer-related cachexia

l '

ttOENTEROL '~rcY

and threefold in patients with septic shock. Plasma albuminlevels do not increase in stressed patients until the inflamma-tory stress remits . For example, albumin levels fail to in-crease in patients with cancer after 21 days of intensivenutritional therapy .66

SERUM PREALBUMIN . Prealbumin is a transport protein forthyroid hormones and exists in the circulation as a retinol-binding prealbumin complex . The turnover rate of this pro-tein is rapid, with a half-life of 2 to 3 days . It is synthesizedby the liver and is catabolized partly by the kidneys . Pro-tein-energy malnutrition reduces the levels of prealbumin,and refeeding restores levels . 67 However, prealbumin levelsdecrease without malnutrition in patients with infections 68and in response to cytokine 69 and stress hormone infusion . 70Renal failure increases levels," whereas liver failure maycause a decrease in levels . The influence of disease-relatedfactors on prealbumin concentration makes it unreliable asan index of nutritional status in hospitalized patients .

CREATININE-HEIGHT INDEX . The amount of creatinine ex-creted in urine provides a measure of skeletal muscle andlean body masses . 72 Approximately 2% of creatine, which isdistributed mainly in muscle cells, is converted daily by anirreversible nonenzymatic reaction to creatinine, which issubsequently excreted unchanged in urine. The creatinine-height index is determined by measuring 24-hour urinarycreatinine excretion in relationship to the patient's heightwhile the patient is consuming a creatine and creatinine-freediet. However, the normal range of values was derived fromhealthy men and women of ideal body weight . Estimates of"ideal" muscle mass may not apply to patients whoseweights do not fall within the ideal range . Furthermore, thevalidity of the creatinine-height index can be affected byinaccurate urine collections, alterations in protein intake, andmedical variables that alter creatinine excretion, independentof muscle mass (e.g ., renal failure, sepsis, trauma, exercise,and steroid therapy) .

Immune Competence

Immune competence, as measured by delayed cutaneous hy-persensitivity (DCH), is altered by severe malnutrition andpatients suffering from severe PEM can become anergic .However, a large number of clinical factors also influenceDCH, making it a poor marker of malnutrition in sick pa-tients. The following factors alter DCH in the absence ofmalnutrition : 1) infection ; 2) illnesses, such as uremia, cir-rhosis, hepatitis, myocardial infarction, trauma, burns, andhemorrhage; 3) medications, such as steroids, immunosup-pressants, cimetidine, and warfarin ; and 4) medical proce-dures, such as anesthesia and surgery .

Discriminant Analysis

Discriminant function analysis, based on retrospective evalu-ation of multiple parameters, has been used to develop pre-dictive equations of clinical outcome .71, 74 Serum proteinconcentrations and DCH are important variables included inthese equations . Buzby and colleagues 73 found that their pre-dictive equation, termed the prognostic nutritional index,

provided a quantitative estimate of postoperative complica-tions when applied prospectively to patients undergoing gas-trointestinal surgery .

Subjective Global Assessment

A clinical method for evaluating nutritional status, termedthe subjective global assessment, encompasses historical,symptomatic, and physical parameters (Table 15-15) .75 . 76

This approach defines malnourished patients as those whoare at increased risk for medical complications . The purposeof this assessment is to determine whether nutrient assimila-tion has been restricted because of decreased food intake,maldigestion, or malabsorption; whether weight loss has oc-curred; whether weight loss in the previous 6 months wasmild (<5%), moderate (5% to 10%), or severe (>10%) ; thepattern of weight loss (e .g ., a patient who had recentlyregained weight would not be considered malnourished) ;whether any effects of malnutrition on organ function andbody composition are present; and whether the patient's dis-ease process influences nutrient requirements (e .g ., high-stress conditions are burns, major trauma, and severe inflam-mation, whereas moderate-stress diseases are mild infectionsand limited malignant tumor) .

The findings of the history and physical examination areused to categorize patients as well nourished (category A),having mild or moderate malnutrition (category B), or hav-ing severe malnutrition (category C) . The rank is assignedon the basis of subjective weighting ; equivocal informationis given less weight than definitive data . Fluid shifts relatedto onset or treatment of edema or ascites must be consideredin interpreting changes in body weight. In general, a patientwho has experienced weight loss and muscle wasting but iscurrently eating well and gaining weight is classified as wellnourished . A patient who has experienced moderate weightloss, continued compromised food intake, continued weightloss, progressive functional impairment, and a moderate-stress illness is classified as moderately malnourished. Apatient who has experienced severe weight loss and contin-ues to have poor nutrient intake, progressive functional im-pairment, and muscle wasting is classified as severely mal-nourished, independent of disease stress . Several studieshave found that the use of subjective global assessment inevaluating hospitalized patients gives reproducible resultsand that there was more than 80% agreement when twoblinded observers assessed the same patient76.77 Detsky andcolleagues 77 found that preoperative subjective global assess-ment was a better predictor of postoperative infectious com-plications than were serum albumin concentration, DCH, an-thropometry, creatinine-height index, and the prognosticnutritional index .

Muscle Function

Impaired muscle function is a manifestation of malnutritionand often occurs before there are structural alterations inmuscle mass. Although muscle function testing is not rou-tinely used in nutritional assessment, it may gain greateracceptance with experience . Electrical stimulation of the ul-nar nerve at the wrist permits the measurement of severalinvoluntary muscle function parameters of the adductor pol-

ChangeDuration =weeksType :

Suboptimal solid dietHypocaloric liquidsStarvation

Gastrointestinal Symptoms (That Persisted for > 2 Weeks) :NoneNauseaVomitingDiarrheaAnorexiaFunctional Capacity

No dysfunctionDysfunctionDuration =weeks

TypeWorking suboptimallyAmbulatory but not workingBedridden

Effect of Disease on Nutritional RequirementsPrimary diagnosis :Metabolic Demand :Low stressModerate stressHigh stressPHYSICAL EXAMINATION (NORMAL, MODERATE, OR SEVERE)

Loss of subcutaneous fat (triceps, chest)Muscle wasting (quadriceps, deltoids)Ankle or sacral edema

AscitesSGA RATINGA = Well nourishedB = Mild or moderate malnutritionC = Severe malnutrition

licis muscle . Studies performed during starvation and refeed-ing in humans suggest that muscle function testing can pro-vide a sensitive measure of the adequacy of nutrientintake." -80 Short-term parenteral nutritional therapy has alsobeen shown to improve respiratory and hand muscle functionin malnourished patients with inflammatory bowel disease 81and malnourished patients awaiting surgery . 8'2 Moreover,muscle function may be a better predictor of clinical out-come than other markers of nutritional status, such as armmuscle circumference, serum albumin concentration, andweight loss . 83-85

Overview of Nutritional Assessment

At present, there is no gold standard for evaluating nutri-tional status, and the reliability of any nutritional assessmenttechnique as a true measure of nutritional status has neverbeen validated . No prospective randomized controlled clini-cal trials have been performed to evaluate whether providingnutrition support improves clinical outcome in patientsjudged to be severely malnourished compared with thosewho are judged to be mildly or moderately malnourished .However, a retrospective subgroup analysis of a large multi-center trial found that parenteral nutrition given preopera-tively to patients with a diagnosis of severe malnutrition bysubjective global assessment or a nutritional risk index(based on serum albumin and body weight change) de-creased postoperative infectious complications . 86 The poten-tial use of muscle function as a measure of nutritional statusrepresents an exciting area for further investigation . Al-though there is strong evidence that muscle function pro-vides an index of both nutritional state and the risk of

medical complications, it is not clear whether the restorationof function leads to an improvement in clinical outcome .The authors recommend that nutritional assessment involve acareful nutritional history and physical examination . In addi-tion, appropriate laboratory studies should be obtained asneeded to further evaluate considerations raised during theclinical examination . The information from this evaluationshould help determine the patient's current clinical conditionand the anticipated duration of inadequate volitional feedingto identify patients who may require oral, enteral, or paren-teral nutrition support (see Chapter 16, Enteral and Paren-teral Nutrition) .

REFEEDING THE MALNOURISHEDPATIENT

Refeeding the severely malnourished patient is necessary toreverse the adverse effects of malnutrition and to preventdeath from starvation . The goal is to inhibit mobilization ofendogenous fuels and use ingested or infused nutrients tomeet body nutritional requirements and rebuild lost nutrientstores .

Refeeding Syndrome

Because of the structural, functional, and metabolic altera-tions caused by previously inadequate food intake, injudi-cious nutritional therapy can have adverse clinical conse-quences known in part as the refeeding syndrome ." , "I Earlyevidence of the refeeding syndrome was reported at the endof World War II, when it was found that oral refeeding of

THE MAL . )I ;RI HEf) P:Al1E',[ : NUTRITIONAL As sSMEtrI'

Table 15-15 1 Features of Subjective Global Assessment (SGA)

HISTORYWeight ChangeLoss in past 6 months: amount = kg; % loss =Change in past 2 weeks : Increase No change Decrease .Dietary Intake Change:No change

chronically semistarved research volunteers and war victimscaused cardiac insufficiency and neurologic complications ."More recently, refeeding abnormalities and serious complica-tions have been reported after aggressive refeeding in hospi-talized cachectic patients .90, 91

Fluid Overload

Decreased cardiac mass, stroke volume, and end-diastolicvolume; bradycardia ; and fragmentation of cardiac myofibrilsare associated with chronic undernutrition . 92-95 In addition,carbohydrate refeeding increases the concentration of circu-lating insulin, which enhances sodium and water reabsorp-tion by the renal tubule . 96 These factors put the severelymalnourished patient at increased risk of fluid retention andcongestive heart failure after nutritional therapy containingwater, glucose, and sodium .

Mineral Depletion

Of the mineral abnormalities associated with refeeding,phosphate depletion has received the most attention . Duringstarvation, phosphorus requirements are decreased because ofthe predominant use of fat as a fuel source . Serum phos-phate is maintained at normal levels by mobilizing bonestores and increasing renal tubular reabsorption . Refeedingwith enteral carbohydrates or glucose-based parenteral for-mulas stimulates insulin release and intracellular uptake ofphosphate .97 Phosphate is needed for protein synthesis andfor the production of phosphorylated intermediates necessaryfor glucose metabolism . 98 These metabolic processes cancause extracellular phosphorus concentration to fall below 1mg/dL within hours of initiating nutritional therapy if ade-quate phosphate is not given . Severe hypophosphatemia,which is associated with muscle weakness, paresthesias, sei-zures, coma, cardiopulmonary decompensation, and death,has occurred in patients receiving enteral or parenteral nutri-tional repletion.9°. 91, 99 . 100 However, it is difficult to deter-mine the contribution of hypophosphatemia to the reportedclinical complications because of other coexistent medicaland nutritional abnormalities .

Potassium and magnesium are the most abundant intracel-lular cations . Loss of body cell mass in the malnourishedpatient causes whole body potassium and magnesium deple-tion. Serum potassium and magnesium concentrations, how-ever, remain normal or near normal during starvation be-cause of their release from tissue and bone stores . Theincreases in protein synthesis rates, body cell mass, andglycogen stores during refeeding require increased intracellu-lar potassium and magnesium . In addition, hyperinsulinemiaduring refeeding increases cellular uptake of potassium andcan cause a rapid decline in extracellular concentrations .'°'

Glucose Intolerance

The adaptive changes during starvation enhance use of fattyacids and ketone bodies for fuel while glucose is conserved .In addition, the ability of insulin to stimulate glucose uptakeand oxidation by peripheral tissues is impaired . 101 Thus, re-feeding with high-carbohydrate meals or large amounts of

parenteral glucose may not be well tolerated initially andmay produce marked elevations in blood glucose, glucosuria,dehydration, and hyperosmolar coma . 102 Furthermore, be-cause of the importance of thiamine in glucose metabolism,carbohydrate refeeding in patients who have thiamine deple-tion can precipitate Wernicke's encephalopathy .l° 3

Gastrointestinal Dysfunction

Starvation and malnutrition cause structural and functionaldeterioration of the GI tract. The total mass and proteincontent of the intestinal mucosa and pancreas are markedlyreduced . Mucosal epithelial cell proliferation rates, the syn-thesis of mucosal and pancreatic digestive enzymes, andintestinal transport and absorption of free amino acids areimpaired, 104 whereas hydrolysis and absorption of peptidesare better maintained . 105 These alterations limit the ability ofthe GI tract to digest and absorb food. When malnutrition issevere, oral refeeding has been associated with increasedincidence of diarrhea and death . 106 However, most of theadverse consequences of starvation on the GI tract disappearafter 1 to 2 weeks of refeeding .

Cardiac Arrhythmias

Ventricular tachyarrhythmias, which can be fatal, occur dur-ing the first week of refeeding . 107 A prolonged QT interval,often documented before death, is a contributing cause ofthe rhythm disturbances . It is not known whether refeedingper se or the cardiac dysfunction underlying malnutritionprecipitated the terminal arrhythmias .

Clinical Recommendations

Initial Evaluation

The severity of complications during refeeding cachectic,chronically semistarved patients emphasizes the importanceof a particularly cautious approach to their nutritional ther-apy, particularly during the first week of therapy when therisk of complications is highest . A careful search for cardio-vascular and electrolyte abnormalities should be performedbefore refeeding . In addition, a search for infections (e .g .,obtaining a white blood cell count, urine analysis and cul-ture, blood cultures, and chest radiograph) should be consid-ered even in the absence of physical findings, because manypatients are not able to mount a normal inflammatory re-sponse .

Initial Supportive Care

Judicious resuscitation with fluids and electrolytes may benecessary before beginning feedings to prevent congestiveheart failure from excessive fluid . Vitamin supplementationshould be given routinely . Severely malnourished patientsare poikilothermic so warm ambient temperature and warm-ing blankets may be necessary to slowly increase core tem-perature. However, if warming blankets are being used, pa-tients must be carefully monitored to avoid hyperthermia .

Feeding Regimen

Patients can be refed orally, by enteral tube feeding, byparenteral nutrition, or through a combination of these meth-ods. Oral or enteral tube feedings are preferred over paren-teral feeding because of fewer serious complications andenhanced gastrointestinal tract recovery . Isotonic feedingsshould be given in small amounts at frequent intervals toprevent overwhelming the body's limited capacity for nutri-ent processing and to prevent hypoglycemia, which can oc-cur during brief nonfeeding intervals . Parenteral supplemen-tation or complete parenteral nutrition may be necessary ifthe intestine cannot tolerate oral/enteral feeding . A combina-tion of many nutrients, particularly nitrogen, phosphorus,potassium, magnesium, and sodium, is needed to restore leanbody mass . Inadequate intake of one nutrient may impairretention of others during refeeding .

Although it is impossible to know the precise nutrientrequirements of individual patients, some general guidelinesare recommended for the first week of refeeding . Fluid in-take should be limited to approximately 800 mL/day plusreplacement for insensible losses . Adjustments in fluid intakeare necessary in patients who have evidence of fluid over-load or dehydration. Changes in body weight provide a use-ful guide for evaluating the efficacy of fluid administration .Weight gain greater than 0 .25 kg/day, or 1 .5 kg/week, prob-ably represents fluid accumulation . Daily calorie intakeshould be approximately 15 to 20 kcal/kg, containing ap-proximately 100 g of carbohydrate and 1 .5 g of protein perkilogram body weight. Sodium should be restricted to ap-proximately 60 mEq or 1 .5 g/day, but liberal amounts ofphosphorus, potassium, and magnesium should be given topatients who have normal renal function tests results . Allother nutrients should be given in amounts needed to meetthe recommended dietary allowance . Daily monitoring ofbody weight, fluid intake, urine output, and plasma glucoseand electrolyte values are critical during early refeeding (first3-7 days), so that nutritional therapy can be appropriatelyadjusted when necessary .

PATIENTS WITH SEVEREMALABSORPTION

Some patients become malnourished because of impairedgastrointestinal tract absorptive capacity . These patients haveinadequate functional small bowel length because of intesti-nal resection or intestinal disease and present the most chal-lenging nutritional management problems for the clinician .The medical management of these patients is often difficultand frustrating, but it can be made much easier by under-standing the physiologic and clinical principles of treatment .Malabsorption syndromes and short bowel syndrome are dis-cussed in greater detail in Chapters 89 and 92, respectively .

Clinical Considerations

The initial assessment of the patient with chronic malabsorp-tion is meant to provide a logical basis for developing atreatment strategy to improve the patient's current clinicalcondition and prevent future complications . The therapeutic

THE MALNOURISHED PATIENT : NUTRITIONAL ASSESSMtNT AND eIVAANY

approach depends on the functioning of the intestinal tract ;the presence of macronutrient, micronutrient, electrolyte, andfluid deficits ; identification of risk factors for future medicalcomplications; the presence of coexisting diseases that ham-per the ability to provide nutritional therapy; and an evalua-tion of factors that affect the patient's daily activities .

A careful review of medical records, operative reports,and radiologic studies is needed to evaluate the absorptivecapacity of the intestine by determining the length of re-maining intestine, the site of intestinal disease or resection,and the presence of diseases that reduce intestinal absorp-tion, such as pancreatic insufficiency or cholestasis . An as-sessment of fluid losses through diarrhea, ostomy output, andfistula volume should be made to help determine fluid re-quirements . Knowledge of fluid losses is also useful in cal-culating intestinal mineral losses by multiplying fluid loss bythe estimated electrolyte concentration in intestinal fluid(Table 15-16) . In patients who do not respond to treatmentas predicted, dynamic studies of intestinal absorptive func-tion may be helpful in adjusting the treatment program . Suchstudies include measuring fat, carbohydrate, and nitrogenbalance and evaluating ostomy, fecal, or fistula mineral andfluid losses .

The urgency for medical intervention is determined bythe severity of hemodynamic and nutritional abnormalities .This requires an evaluation for volume depletion, weightloss, and specific nutrient deficiencies . In addition to stan-dard laboratory tests to evaluate for anemia (iron, folate, orvitamin B 12 deficiency), prolonged prothrombin time (vita-min K deficiency), and electrolyte abnormalities, more so-phisticated measurements to determine vitamin and tracemineral status can be obtained when deficiencies are sus-pected clinically. Bone mineral densitometry may be usefulin many patients to establish a baseline and to screen forunrecognized bone mineral depletion . An accurate dietaryhistory obtained by using food records is useful in evaluat-ing nutrient requirements in nutritionally stable patients andin identifying dietary inadequacies in those with nutrientdeficiencies .

Finally, it is also important to consider specific problemsthat interfere with the patient's quality of life . Maintainingadequate nutritional status with oral feedings at the cost ofmassive diarrhea and frequent bowel movements may beunacceptable to the patient with an active social or profes-sional life outside the home . In this patient, parenteral sup-plementation may be necessary to improve the quality oflife .

*Average values are listed; these can vary considerably from patient to patient .

Table 15-16 1 Electrolyte Concentrationsin Gastrointestinal Fluids*

LOCATIONNa

(mEq/L)K

(mEq/L)CI

(mEq/L)HCO3(mEq/L)

Stomach 65 10 100Bile 150 4 100 35Pancreas 150 7 80 75Duodenum 90 15 90 15Mid-small bowel 140 6 100 20Terminal ileum 140 8 60 70Rectum 40 90 15 30

Treatment

The goals of therapy are to control diarrhea ; maintain fluid,electrolyte, and nutritional homeostasis ; treat and preventmedical complications; and maximize the quality of life . Thetherapeutic approach depends on the results of the clinicalevaluation. Initial therapy often requires subsequent modifi-cation using a trial-and-error approach, because of individualvariability in absorptive function, continued intestinal adapta-tion, and the development of new medical complications ordisease progression . Continued clinical monitoring is criticalso that medical and nutritional therapy can be adjusted whennecessary .

Control of Diarrhea

Diarrhea is often caused by a combination of factors, includ-ing increased gastrointestinal secretions, decreased intestinaltransit time, and osmotic stimulation of water secretion byunabsorbed luminal contents . Therefore, therapy for diarrheainvolves limiting endogenous secretions, slowing motility,and improving solute absorption .

The stomach normally produces approximately 2 .5 L offluid per day, which is absorbed by the small bowel. Gastricsecretion and, in some patients, gastric hypersecretion maycontribute to diarrhea. The use of Hz receptor antagonists orproton pump inhibitors may be necessary to reduce gastricsecretions . The presence of acidic jejunostomy or ileostomycontents after meals is a clear indication for acid-reductiontherapy."" Large dosages, twice the normal amount used forthe treatment of peptic ulcer disease or reflux, may be re-quired for adequate control in certain patients because ofreduced drug absorption .

The long-acting somatostatin analog, octreotide acetate(Sandostatin) can decrease small intestine secretions . Ther-apy with octreotide has been shown to decrease ostomy orstool volume (by 500 to 4000 g/day), decrease sodium andchloride output, and prolong small bowel transit time inpatients with short bowel syndrome . 109-111 However, octreo-tide therapy does not improve absorption of macronutrientsand other minerals . In addition, octreotide is expensive, mustbe given by subcutaneous injections, can decrease appetite,impair fat absorption,' 12 increase the risk of gallstones, 1 'and decrease the use of amino acids for splanchnic proteinsynthesis .' 14 Nevertheless, in patients who have persistentlarge volume intestinal output despite standard antidiarrhealtherapy, a trial of 100 µg octreotide injected subcutaneouslythree times a day with meals may be useful .

Opiates are the most effective means for slowing intesti-nal motility and act by delaying gastric emptying, decreasingperistalsis of the small and large intestine, and increasinganal sphincter tone . Loperamide (Imodium) should be triedfirst, because it is metabolized on first pass by the liver anddoes not easily cross the blood-brain barrier, thereby limitingits side effects and potential for drug dependence . If loper-amide is not effective, other opiates, such as codeine ordeodorized tincture of opium (10 to 25 drops every 6 hours),should be considered . In addition, the combination of ananticholinergic drug and an opiate may be beneficial . Wehave found that capsules containing 25 mg powdered opiumand 15 mg powdered belladonna are a potent combination .

However, these capsules are not commercially available andrequire a willing pharmacist to make them . Diphenoxylatewith atropine (Lomotil) is an effective agent, but it is expensive and inconvenient if large doses are needed .

Foods and medications that cause diarrhea should beavoided. Traditionally, the recommendation has been to de-crease or eliminate lactose-containing foods because of thereduction in intestinal lactase in patients who have had intes-tinal resection . However, patients with jejunostomies with 15to 150 cm of jejunum remaining can tolerate 20-g lactoseloads as milk or yogurt ."s Although lactose was better ab-sorbed from yogurt than from milk, there was no differencein clinical symptoms . Foods that have laxative effects, suchas caffeine-containing drinks and diet products containingosmotically active sweeteners (sorbitol, xylitol, and manni-tol), should be avoided . Medications that contain magnesiumor sorbitol can also contribute to diarrhea . 110

Enteral Feeding

The ability to use the gut to provide nutritional therapydepends on intestinal absorptive function as well as on thepatient's ability to feed without producing adverse symp-toms. Patients with nausea, vomiting, abdominal pain, orsevere diarrhea may be unable to tolerate enteral feedingregardless of intestinal absorptive capacity . Specific foodsthat cause gastrointestinal complaints should be avoided .However, it is important to evaluate objectively the validityof these complaints to prevent the unnecessary withdrawal ofnutritious foods . Patients with gluten-sensitive enteropathyrequire a strict gluten-free diet .

The goal of feeding is to provide the patient with allrecommended nutritional requirements . The amount of in-gested nutrients needed to reach this goal depends on thenormal recommended dietary allowances modified by an es-timate of absorptive function and intestinal losses. This usu-ally requires ingestion of large amounts of fluid, calories.protein, vitamins, and minerals . Even in patients with severeshort bowel syndrome, total parenteral nutrition may not beneeded when vitamin and mineral supplements and largeamounts of calories and protein are provided enterally ."'Increasing the time that food is in contact with the intestinemay enhance absorption in patients with limited absorptivefunction. For this reason, total dietary intake should be di-vided into at least six meals per day . If this is unsuccessful,defined liquid formulas ingested between meals or adminis-tered by continuous tube feedings at night may prevent theneed for parenteral nutrition . In general, most patients withsevere malabsorption must ingest 40 to 60 kcal/kg/day and1 .2 to 1 .5 g of protein/kg/day . Suggested guidelines forvitamin and mineral supplementation are outlined in Table15-17. The needs of each patient, however, can be deter-mined only by experimentation with different dietary manip-ulations .

FAT INTAKE . Fat intake should not be restricted in patientswith a jejunostomy or ileostomy despite the presence ofsteatorrhea. A high-fat, low-carbohydrate diet has beenfound to be comparable to a low-fat, high-carbohydrate dietwith regard to total fluid, energy, nitrogen, sodium, potas-sium, and divalent ion absorption in patients with shortbowel syndrome .' 11-120 Furthermore, a high-fat diet facili-

Prenatal multivitamin withminerals*

Vitamin D*

Calcium*

Vitamin B 12 t

Vitamin AtVitamin Kt(Mephyton; Aqua-MEPHYTON)

Vitamin Et (Aquasol E)Magnesium gluconatet (Ma-gonate) or magnesium ox-ide capsules (URO-MAG)

Magnesium sulfatet

Zinc gluconate or zinc sul-fatet

Ferrous sulfatetIron dextrant

1 tab qd po

50,000 U 2-3 times per

poweek

500 mg elemental cal-

pocium tid to qid

1 mg qd

po100-500 µg q 1-2 mo

s.c .10,000 to 50,000 U qd

po5 mg/d

po5-10 mg/wk

S .C .

100 U/d

po108-169 mg elemental

pomagnesium qid

290 mg elemental mag-

IM/IVnesium 1-3 timesper wk

25 mg elemental zinc qd

poplus 100 mg elementalzinc/L intestinal output

60 mg elemental iron tid

poX100 mg elemental iron

IVper day based on for-mula or table

*Recommended routinely for all patients .tRecommended for patients with documented nutrient deficiency or malab-

sorption .IM, intramuscular ; IV, intravenous ; po, oral ; s .c ., subcutaneous .

tates the ingestion of more calories . Limiting fat intake,however, may decrease gastrointestinal symptoms, colonicwater secretion, hyperoxaluria, and divalent certain losses inpatients who have steatorrhea and an intact colon . 121, 122

Theoretically, medium-chain triglycerides (MCTs) areuseful as a feeding supplement in patients who have im-paired fat absorption, because they are rapidly hydrolyzedand do not require bile salts and micelle formation for ab-sorption . 123 However, many patients do not find MCT oilpalatable. Furthermore, MCT oil can cause nausea, vomiting,and abdominal discomfort . A dosage of 1 tablespoon (15mL) three to four times daily, providing a total of approxi-mately 500 kcal, is usually the maximal amount tolerated .

PREDIGESTED FORMULAS . Predigested formulas-that is;monomeric (elemental) and oligomeric formulas-have beenrecommended for patients with short bowel syndrome . Theo-retically, these formulas, which contain nitrogen in the formof free amino acids or small peptides, are absorbed moreefficiently over a shorter length of intestine than are poly-meric formulas or whole food . However, the clinical efficacyof these formulas is not clear. Two prospective trials, usinga randomized cross-over design, have evaluated the use ofpredigested formulas in patients with a jejunostomy and lessthan 150 cm of residual small bowel.120• 124 McIntyre andcolleagues 120 found no difference in nitrogen or total calorieabsorption between a polymeric and an oligomeric diet. Incontrast, Cosnes and coworkers 124 found that nitrogen ab-

THE MALNOURIM,t t r PAM N3 : Nut RITK?NAt AsSE s 2 , rtNtn

sorption, but not total calorie absorption, was greater when apeptide-based diet was consumed than when a diet contain-ing whole proteins was consumed. However, it is not knownwhether the increase in nitrogen absorption led to an im-provement in protein metabolism or nitrogen balance,because these parameters were not measured . Blood urea ni-trogen and urinary urea excretion were greater during pep-tide-based diet feeding than during whole protein diet inges-tion, suggesting that the absorption of additional amino acidsstimulated amino acid oxidation . Therefore, at present thereis insufficient clinical evidence to justify the routine use ofexpensive predigested formulas in patients with short bowelsyndrome .

ORAL REHYDRATION THERAPY. A subset of patients, usu-ally those with 50 to 100 cm of jejunum that either ends ina jejunostomy or is anastomosed to the midtransverse ordistal colon, cannot maintain fluid and electrolyte homeosta-sis but may be able to absorb adequate protein and calories .These patients may benefit from oral rehydration therapythat takes advantage of the sodium-glucose cotransporterpresent in the brush border of intestinal epithelium . 125 Fre-quent ingestion of small volume feedings of an isotonicglucose or starch-based electrolyte solution 126 stimulates ac-tive sodium transport across the intestine, whereas waterfollows passively by solvent drag . 127 Data from studies inanimals and patients with short bowel syndrome suggest thatsodium and water absorption is maximal from solutions con-taining 90 to 120 mmol/L of sodium .' 25

Unfortunately, most commercially available oral rehydra-tion formulas and sport drinks contain lower sodium concen-trations and are not optimal for patients with short bowelsyndrome. However, inexpensive and more effective solu-tions can be made by patients at home (Table 15-18). Dailyoral administration of 1 to 2 L of rehydration solutions hasbeen successful in correcting fluid and electrolyte abnormali-ties and allows intravenous supplementation to be discontin-ued in patients who have had extensive intestinal resec-tion. 12s-111 In some patients, oral rehydration therapy hasdecreased ostomy output by 4 L/day . 131

MAJOR MINERALS . Major minerals should be supplementedas needed, depending on the assessment of body content .Maintaining magnesium homeostasis is often difficult, be-cause magnesium is poorly absorbed and enteral supplemen-tation with magnesium salts increases diarrhea . Enteric-coated magnesium supplements should not be used, becausetheir delayed release reduces contact with the intestine forabsorption . 132

Soluble magnesium salts, such as magnesium gluconate,are better tolerated and absorbed than are other magnesiumcomplexes . In some patients, magnesium is best given inliquid form as magnesium gluconate (Fleming Inc ., St .Louis, MO) and can be added to a oral rehydration solutionin doses of 18 to 27 mmol (432 to 648 mg of elementalmagnesium) per day . This solution should be sipped, notingested as a bolus, to maximize absorption and avoid diar-rhea. Normal serum magnesium levels do not exclude thepossibility of magnesium deficiency . The percentage of mag-nesium excreted in urine after infusion may prove to be abetter index of body magnesium stores; excretion of lessthan 80% of infused magnesium suggests whole body mag-nesium depletion . 133

Table 15-17 1 Guidelines for Vitamin and MineralSupplementation in Patients with SevereMalabsorption

SUPPLEMENT(REPRESENTATIVE

PRODUCT) DOSE ROUTE

Table 15-18 1 Characteristics of Selected Oral Rehydration Solutions

IN GASTkOENTFR(_11 Q( r

Equalyte also contains fructooIigosaccharides .WHO (World Health Organization) formula : Mix 3/4 tsp sodium chloride, 1/2 tsp sodium citrate, 1/4 tsp potassium chloride, and 4 tsp glucose (dextrose) in 1 L (4 1/4

cups) of distilled water .Washington University formula : Mix 3/4 tsp sodium chloride, 1/2 tsp sodium citrate, and 3 tbsp + 1 tsp Polycose powder in 1 L (4 1/4 cups) of distilled water .Mix formulas with sugar-free flavorings as needed for palatability .

Supplemental calcium is given routinely because of bothreduced intestinal absorption and the limited calcium contentof low-lactose diets . Plasma levels of calcium are usuallymaintained by mobilizing bone stores unless there is concur-rent magnesium or vitamin D deficiency . Therefore, urinarycalcium excretion, which should be greater than 50 mg in 24hours, is a more reliable index of calcium status . Most pa-tients require approximately 1 .5 to 2 g of elemental calciumdaily. Although it has been suggested that calcium citrate isabsorbed better than calcium carbonate, 114 most studies donot demonstrate any differences in calcium bioavailabilityfrom calcium ingested as carbonate, citrate, gluconate, lac-tate, or sulfate salt .t35, 136 However, the amount of calciumpresent in each calcium salt differs significantly, which influ-ences the number of tablets needed each day .

Trace Minerals . Data regarding trace mineral requirements inpatients with malabsorption disorders are limited . With theexception of zinc and iron, absorption of trace minerals fromingested foods or liquid formulas is often adequate to pre-vent overt deficiency syndromes . Zinc deficiency is common,and often subclinical, in patients with malabsorption . Largedosages of oral zinc supplements may become necessary,because zinc losses are often high and zinc absorption islow. Zinc gluconate is tolerated well and does not cause thegastric distress caused by zinc sulfate . Zinc should not begiven with meals, because absorption is reduced by food."'Daily zinc supplementation of 25 mg plus an additional 100mg/L (or 100 mg/kg) of ostomy or diarrheal output isneeded to maintain zinc homeostasis . 138 Thus, many patientsrequire approximately 150 mg of elemental zinc per day .Although zinc ingestion reduces copper absorption and cancause clinically significant copper deficiency, 139 additionalcopper intake usually is not needed because of the lowefficiency of zinc absorption . Treating iron deficiency withoral preparations can be difficult . We recommend a liquidform of ferrous sulfate (300 mg/5 mL containing 60 mg ofelemental iron) mixed in orange juice four times per day .Diluting ferrous sulfate liquid prevents staining of teeth, andthe ascorbic acid present in orange juice enhances iron ab-sorption . Some patients, however, require intermittent admin-istration of parenteral iron .

Vitamins . Patients with malabsorption can usually absorb ad-equate amounts of most water-soluble vitamins from their

diet, but patients with steatorrhea and bile acid depletionhave difficulty absorbing fat-soluble vitamins . Vitamin Kdeficiency is rarely a clinical problem unless patients arereceiving antibiotics . However, large doses of vitamins A, D,and E may be required to maintain normal body concentra-tions. Liquid vitamins present in water-miscible and water-soluble forms are more effective than are standard vitaminsin pill form. An assessment of vitamin status should be usedto guide therapy .

PARENTERAL FEEDING. Parenteral nutrition may be neces-sary to provide fluids, specific nutrients, or complete nutri-tional requirements in patients who cannot maintain normalhydration, electrolyte balance, or nutritional status with oralfeeding. Some general guidelines are useful in decidingwhich patients require parenteral therapy . Patients in whomurine output is less than I L day are at increased risk fordeveloping renal dysfunction and should receive intravenousfluids. Adequate levels of certain minerals-such as magne-sium, potassium, and zinc-and fat-soluble vitamins are dif-ficult to maintain with oral feedings in patients with severesteatorrhea or large intestinal fluid output and may requireparenteral supplementation . Magnesium sulfate can be in-jected intramuscularly at a dose of 12 mmol (290 mg ofelemental magnesium) one to three times per week if at-tempts at oral therapy are unsuccessful . Intravenous infusionof magnesium is preferred, however, because intramuscularinjections are painful and can cause sterile abscesses .Monthly intramuscular injections of vitamin B 12 (200 mg/month) are required in patients who have evidence of vita-min B12 malabsorption . In patients who have evidence of, orare at high risk for, vitamin K-associated hypoprothrombin-emia, 5 to 10 mg of vitamin K should be given intramuscu-larly or intravenously each week . In some patients, totalparenteral nutrition may be lifesaving or may be needed tolimit diarrhea and achieve an acceptable quality of life .

REFERENCES

1 . Martin WH, Klein S : Use of endogenous carbohydrate and fat as fuelsduring exercise . Proc Nutr Soc 57 :49, 1998 .

2. Harris JA, Benedict FG : Standard basal metabolism constants forphysiologists and clinicians . In A Biometric Study of Basal Metabo-lism in Man. Publication 279, The Camegie Institute of Washington .Philadelphia, JB Lippincott, 1919, p 223 .

Equalyte 78m 22 68 1900 mg 100 25 305CeraLyte 70 70 20 98 30 165 40 235CeraLyte 90 90 20 98 30 165 40 260Pedialyte 45 20 35 30 100 20 300Rehydralyte 74 19 64 30 100 25 305Gatorade 20 3 N/A N/A 210 45 330WHO 90 20 80 30 80 20 200Washington University 105 0 100 10 85 20 250