Metabolic Response to

Starvation and Trauma:

Nutritional
Requirements

Ifiq Budiyan Nazar

Metabolic Response to Fasting
I II III IV V
GLUCOSE UTILIZED (g/hora)

40 Exogenous
Glycogen
Gluconeogenesis
30

20

10

LEGEND I II III IV V
FUEL FOR GLUCOSE, GLUCOSE,
BRAIN
GLUCOSE GLUCOSE GLUCOSE
KETONES KETONES

Ruderman NB. Annu Rev Med 1975;26:248

Hypermetabolic Response to
Stress-Pathophysiology

Algorithm content developed by John Anderson, PhD, and Sanford C. Garner, PhD, 2000.
Respon Stress

Terdapat 3 fase : Ebb phase,

Flow phase dan
recovery/resolution phase
Ebb Phase : respon seketika
setelah trauma
Flow Phase: Fase setelah ebb
phase berakhir
Ebb Phase:

Instabilitas hemodinamik,
ekstremitas dingin, hipometabolik
Waktu: bervariasi, 12-24 jam, paling
lama 2 hari
Tergantung cukupnya resusitasi
cairan
Cardiac output menurun
Konsumsi oksigen berkurang
Penggunaan substrat menurun
Penurunan fungsi sel
Metabolic Response to Trauma:
Ebb Phase
Characterized by hypovolemic shock
Priority is to maintain life/homeostasis
Cardiac output
Oxygen consumption
Blood pressure
Tissue perfusion
Body temperature
Metabolic rate

Cuthbertson DP, et al. Adv Clin Chem 1969;12:1-55

Welborn MB. In: Rombeau JL, Rolandelli RH, eds. Enteral and Tube Feeding. 3rd ed. 1997
Fase Flow

Respon metabolik yang dapat

mengubah penggunaan energi
dan protein
Untuk menjaga fungsi organ
Dan memperbaiki kerusakan
jaringan
Peningkatan konsumsi oksigen,
tingkat metabolisme
 Metabolic Response to Trauma:
Flow Phase
Catecholamines
Glucocorticoids
Glucagon
Release of cytokines, lipid mediators
Acute phase protein production

Cuthbertson DP, et al. Adv Clin Chem 1969;12:1-55

Welborn MB. In: Rombeau JL, Rolandelli RH, eds. Enteral and Tube Feeding. 3rd ed. 1997
 Metabolic Response
to Starvation and Trauma

Starvation Trauma or Disease

Metabolic rate
Body fuels conserved wasted
Body protein conserved wasted
Urinary nitrogen
Weight loss slow rapid

The body adapts to starvation, but not in the

presence of critical injury or disease.
Popp MB, et al. In: Fischer JF, ed. Surgical Nutrition. 1983.
 Metabolic Reaction to Starvation

Hormone Source Change in Secretion

Norepinephrine Sympathetic Nervous System
Norepinephrine Adrenal Gland
Epinephrine Adrenal Gland
Thyroid Hormone T4 Thyroid Gland (changes to T3

peripherally)

Landberg L, et al. N Engl J Med 1978;298:1295.

Hormonal and Cell-Mediated
Response
Terjadi peningkatan signifikan
produksi glukosa dan uptake
sekunder glukoneogenesis, dan
Peningkatan level hormon
Peningkatan uptake asam amino
hepatik
Sintesa Protein
Percepatan pemecahan protein otot
Metabolic Response to Trauma

Fatty Acids
Fatty Deposits

Endocrine Liver & Muscle

(glycogen) Glucose
Response

Muscle
(amino acids) Amino Acids
Metabolic Response to Trauma

28
Nitrogen Excretion (g/day)

24
20
16
12
8
4
0
10 20 30 40
Days
Long CL, et al. JPEN 1979;3:452-456
Severity of Trauma: Effects on
Nitrogen Losses and Metabolic
Rate
Major
Ciruga
Surgery
mayor

Moderate
Quemadurato Severe
moderadaBurn
a grave
Nitrogen Loss in Urine

Severe
Sepsis
grave
Sepsis
Infeccin
Infection

Elective
Ciruga
electiva
Surgery

Basal Metabolic Rate

 Metabolic Changes in
Starvation

From Simmons RL, Steed DL: Basic science review for surgeons, Philadelphia, 1992, WB Saunders.
 Starvation vs. Stress
Respon Metabolik terhadap stress
berbeda dg respon terhadap kelaparan.
Starvation = penurunan energi
expenditure, menggunakan energi
alternatif, penurunan protein wasting,
penggunaan cadangan glikogen pada 24
jam pertama
Late starvation = fatty acids, ketones, and
glycerol provide energy for all tissues
except brain, nervous system, and RBCs
Energy Expenditure in Starvation
12
Nitrogen Excretion (g/day)

8 Normal Range

4 Partial Starvation

Total Starvation
0
10 20 30 40

Days
Long CL et al. JPEN 1979;3:452-456
Metabolic Response to Trauma

Ebb
Ebb Flow
Flow
Phase Phase
Energy Expenditure

Phase Phase

Time

Cutherbertson DP, et al. Adv Clin Chem 1969;12:1-55

Hormonal Stress Response

Aldosteronecorticosteroid
menyebabkan retensi sodium
Antidiuretic hormone (ADH)
merangsang absorpsi air di
tubular renal
Mempertahankan air dan
garan untuk menunjang
sirkulasi volume darah
Hormonal Stress
Responsecontd

ACTHacts on adrenal cortex

to release cortisol (mobilizes
amino acids from skeletal
muscles)
Catecholaminesepinephrine
and norepinephrine from renal
medulla to stimulate hepatic
glycogenolysis, fat
mobilization, gluconeogenesis
 Cytokines

Interleukin-1, interleukin-6,
and tumor necrosis factor
(TNF)
Released by phagocytes in
response to tissue damage,
infection, inflammation, and
some drugs and chemicals
Pemakaian energi

Pada fase flow, pemakaian energi

meningkat, seiring peningkatan
tingkat metabolisme
Konsumsi oksigen bertambah,
seiring bertambahnya oksidasi zat
gizi mayor (karbohidrat, lemak dan
asam amino)
Peningkatan sesuai dengan
besarnya trauma: minimal hingga
dua kali lipat pada luka bakar 40%
 Dasar penatalaksanaan :
menjaga hemodinamik,
optimalisasi strategi
ventilasi, pemberian cairan,
mengontrol fungsi organ, dan
pemberian nutrisi
 Peningkatan tingkat
metabolisme mobilisasi
simpanan energi
Glikogen (cadangan
karbohidrat): menurun dalam
24 jam setelah trauma
simpanan lemak dan protein
menjadi sumber energi utama
glukoneogenesis
 Peningkatan ekskresi nitrogen
dalam bentuk urea, sesuai
besarnya trauma
Juga dalam bentuk kreatinin,
ammonia, asam urat, dan asam
amino
kehilangan massa otot
signifikan setelah trauma
 Cadangan lemak juga
termobilisasi dan teroksidasi
pada keadaan hipermetabol

Peningkatan hormon
glukokortikoid, katekolamin,
dan glukagon
Metabolisme Protein

Protein adalah salah satu cadangan

energi
Pada trauma, cadangan ini termobilisasi
Terjadi pengeluaran asam amino dari dari
perifer dan peningkatan ekskresi nitrogen
Peningkatan sesuai luas dan beratnya
trauma
Terjadi keseimbangan nitrogen negatif
Sesuai juga dengan peningkatan
konsumsi oksigen
 Kehilangan protein jika tidak cepat
dikoreksi akan menyebabkan hilangnya
massa otot dan berikutnya disfungsi
atau kegagalan organ
Terjadi peningkatan pemecahan protein
terutama myofibrilar protein,
berkurangnya sintesis protein dan
pencegahan pengambilan protein
Melibatkan: glukortikoid, sitokin, Tumor
Necrosis Factor (TNF), interleukin-1 (IL-1)
 Metabolisme glukosa

Pada sepsis dan trauma terjadi

hiperglikemia
Oleh karena adanya glukoneogenesis
di hepar dan penurunan uptake
glukosa oleh karena penurunan
insulin
Pada fase ebb, insulin berkurang tapi
meningkat setelah fase flow namun
tetap relatif rendah dibanding normal
 Gangguan metabolisme glukosa
mengurangi uptake glukosa oleh otot
rangka dan perubahan glukosa menjadi
asam lemak di jaringan adiposa
Terjadi keadaan resistensi insulin perifer
Adanya kortisol dan katekolamin gagal
menghambat lajunya glukoneogenesis
dan glikogenolisis
Hal ini perlu untuk menjaga ketersediaan
glukosa untuk organ seperti: SSP, ginjal,
jaringan luka dan sel darah yang penting
untuk kelangsungan hidup
 Selama respon stress, sumber
glukosa lain adalah glikolisis anaerob
pada otot dan jaringan hipoksis
(luka) yang memproduksi laktat
Laktat dapat diubah menjadi glukosa
dengan Cory Cycle yang meningkat
pada luka bakar dan trauma
Pada luka bakar: laktat adalah
substrat glukoneogenik terpenting
Metabolisme lemak

Lemak adalah sumber energi

utama
Pada stress dan trauma, mobilisasi
dan penggunaan lemak dapat
menjaga agar cadangan protein
tidak cepat berkurang
Leptin, hormon yang men-stimulasi
oksidasi asam lemak, berhubungan
dengan sitokin adalah stress-
related hormone
 Leptin dan sitokin peningkatan asam
lemak bebas dan trigliserida pada darah
Pada stress dan trauma, lebih banyak
terjadi oksidasi lemak sebagai sumber
energi
Yang ditandai penurunan Respiratory
Quotient oksidasi lemak. RQ Normal;
0,85
Peningkatan jumlah asam lemak dapat
menjadi sumber energi untuk berbagai
jaringan, kecuali darah dan otak
 Hypermetabolic Response to Stress
Medical and Nutritional Management

Algorithm content developed by John Anderson, PhD, and Sanford C. Garner, PhD, 2000. Updated by Maion F. Winkler and
Ainsley Malone, 2002.
Metabolic Response to Surgical Trauma

Metabolic Changes after Trauma

Muscle

Alanine / Pyruvate
Glucose Brain

Glutamine
Glycerol Gluconeogenesis

Fat Ketogenesis Ketones

AGL Liver
Ureagenesis

Ketones Urea

NH3
Kidney
Intestine
Determining Calorie
Requirements

Indirect calorimetry
Harris-Benedict x stress factor x activity factor
25-30 kcal/kg body weight/day
 Metabolic Response to Starvation
and Trauma: Nutritional
Requirements
Injury Stress Factor Example:
Minor surgery 1.00 1.10 Energy requirements for
Long bone fracture 1.15 1.30 patient with cancer in bed
Cancer 1.10 1.30
Peritonitis/sepsis 1.10 1.30 = BEE x 1.10 x 1.2
Severe infection/multiple trauma 1.20 1.40
Multi-organ failure syndrome 1.20 1.40
Burns 1.20 2.00
Activity Activity Factor
Confined to bed 1.2
Out of bed 1.3

ADA: Manual Of Clinical Dietetics. 5th ed. Chicago: American Dietetic Association; 1996
Long CL, et al. JPEN 1979;3:452-456
Metabolic Response to
Overfeeding
Hyperglycemia
Hypertriglyceridemia
Hypercapnia
Fatty liver
Hypophosphatemia, hypomagnesemia, hypokalemia

Barton RG. Nutr Clin Pract 1994;9:127-139

Macronutrients during Stress
Carbohydrate
At least 100 g/day needed to prevent ketosis
Carbohydrate intake during stress should be between
30%-40% of total calories
Glucose intake should not exceed
5 mg/kg/min

Barton RG. Nutr Clin Pract 1994;9:127-139

ASPEN Board of Directors. JPEN 2002; 26 Suppl 1:22SA
Macronutrientes during Stress
Fat
Provide 20%-35% of total calories
Maximum recommendation for intravenous lipid
infusion: 1.0 -1.5 g/kg/day
Monitor triglyceride level to ensure adequate lipid
clearance

Barton RG. Nutr Clin Pract 1994;9:127-139

ASPEN Board of Directors. JPEN 2002;26 Suppl 1:22SA
Macronutrients during Stress

Protein
Requirements range from 1.2-2.0 g/kg/day during stress
Comprise 20%-30% of total calories during stress

Barton RG. Nutr Clin Pract 1994;9:127-139

ASPEN Board of Directors. JPEN 2002;26 Suppl 1:22SA
 Determining Protein Requirements
for Hospitalized Patients

Stress Level No Stress Moderate Stress Severe Stress

Calorie:Nitrogen Ratio > 150:1 150-100:1 < 100:1

Percent Potein / Total < 15% 15-20% > 20%
Calories protein protein protein

Protein / kg Body Weight 0.8 1.0-1.2 1.5-2.0

g/kg/day g/kg/day g/kg/day
Role of Glutamine in Metabolic
Stress
Considered conditionally essential for critical patients
Depleted after trauma
Provides fuel for the cells of the immune system and GI
tract
Helps maintain or restore intestinal mucosal integrity

Smith RJ, et al. JPEN 1990;14(4 Suppl):94S-99S; Pastores SM, et al. Nutrition 1994;10:385-391
Calder PC. Clin Nutr 1994;13:2-8; Furst P. Eur J Clin Nutr 1994;48:607-616
Standen J, Bihari D. Curr Opin Clin Nutr Metab Care 2000;3:149-157
 Role of Arginine in Metabolic
Stress
Provides substrates to immune system
Increases nitrogen retention after metabolic stress
Improves wound healing in animal models
Stimulates secretion of growth hormone and is a precursor
for polyamines and nitric oxide
Not appropriate for septic or inflammatory patients.

Giving arginine to a septic patient is like putting gasoline on an

already burning fire.
- B. Mizock, Medical Intensive Care Unit, Cook County Hospital, Chicago, IL

Barbul A. JPEN 1986;10:227-238; Barbul A, et al. J Surg Res 1980;29:228-235

Key Vitamins and Minerals

Vitamin A Wound healing and tissue repair

Vitamin C Collagen synthesis, wound healing
B Vitamins Metabolism, carbohydrate utilization
Pyridoxine Essential for protein synthesis
Zinc Wound healing, immune function, protein
synthesis
Vitamin E Antioxidant
Folic Acid, Required for synthesis and replacement of red
Iron, B12 blood cells
Summary

Metabolic response to starvation is an adaptive

mechanism
Nutritional requirements increase during trauma