-

Systemic Response to Injury and Metabolic Support

388-431, 388-432, 388-433
..

1.
stress
2.
3.

4.

1. The detection of cellular injury

2. Central nervous system regulation of inflammatory in response to injury
3. Neuroendocrine response to injury
4. Mediators of inflammation: Cytokines, Eicosanoids
5. Surgical Metabolism: Fat, Carbohydrate, Protein
6. Nutrition for surgical patient: Energy expenditure, Nutrients and Energy
requirement, Route of administration, monitoring and complications
1
1. 45
2. 15

1. Systemic Response to Injury and Metabolic Support

2. CAI
: MCQ, OSCE

1. Brunicardi C, Anderson D, Billiar T, et al. Schwartz Principle of Surgery Edition 10.

United States of America, McGraw-Hill Education. 2015;13-64.
2. Townsend C, Beauchamp R, Evers B, et al. Sabiston Textbook of Surgery Edition
19. Canada, Elsevier Saunders. 2012;120-50.
3. Rojratsirikul C, Sangkhathat S, Patrapinyokul S. Application of Subjective Global
Assessment as a screening tool for malnutrition in Pediatric Surgical Patients. J
med Assoc Thai. 2004; 87(8):939-46.

Systemic Response to Injury and Metabolic Support 2

Systemic Response to Injury and Metabolic Support

.

(local response)
(systemic response)
Homeostasis
systemic inflammation
multiple organ failure 30

acute inflammatory
response
complex pathways

The detection of cellular injury

(innate immune system)
systemic inflammatory response
2 acute proinflammatory response anti-inflammatory
response
(multiple organ failure)
systemic inflammation
homeostasis
counterregulatory anti-inflammatory response syndrome (CARS)
late multiple organ failure 1
systemic inflammatory response


damage-associated
molecular patterns (DAMPs) pathogen-associated molecular patterns (PAMPs)
receptor receptor
toll-like receptor family 1

Systemic Response to Injury and Metabolic Support 3

1 systemic inflammatory response syndrome(SIRS)

counterregulatory anti-inflammatory response
syndrome(CARS)1
1
1
Damage-associated molecular patterns (DAMPs) and their receptors
DAMP MOLECULE

PUTATIVE RECEPTOR(S)

HMGB1

TLRs (2,4,9), RAGE

Heat shock proteins

TLR2, TLR4, CD40, CD14

S100 protein

RAGE

Mitochondrial DNA

TLR9

Hyaluronan

TLR2, TLR4, CD44

Biglycan

TLR2 and TLR4

Formyl peptides (mitochondrial)

Formyl peptide receptor 1

IL-1

IL-1 receptor

HMGB1 = high-mobility group protein B1; TLR = Toll-like receptor; IL = interleukin; RAGE =
receptor for advanced glycosylation end

Systemic Response to Injury and Metabolic Support 4

DAMPs
stress DAMPs
(innate immune cell) antigen-presenting cells DAMPs highmobility group protein B1 (HMGB1)
cytokines Tumor necrosis factor (TNF) Interleukin-1
30 HMGPB1 Injury
Severity Score TNF

Central nervous system regulation of inflammatory in response to injury

mediators
2

2 1
DAMPs
endothelium neuron glial cell ventricle
blood brain barrier
proinflammatory mediator cytokines, chemokines,
complement system (antiinflammatory response) hypothalamus-pituitary-adrenal (HPA) axis
Glucocorticoid

Systemic Response to Injury and Metabolic Support 5

afferent neural fibers

vagus nerve neuron hypothalamus
HPA axis brain stem dorsal motor nucleus axon
visceromotor vagus nerve feedback mechanism
Cholinergic signals acetylcholine
vagus proinflammatory
cytokines CD4+ T cell acetylcholine feedback
mechanism splenic catecholaminergic nerve fibers
celiac plexus acetylcholine
cholinergic receptor immune cell

Neuroendocrine Response to Injury

2
HPA axis glucocorticoid sympathetic nervous system
catecholamines, epinephrine norepinephrine
HPA axis
growth hormone, macrophage inhibitory factor, aldosterone insulin
HPA axis
Hypothalamic Regulation: Corticotropin-releasing hormone, Thyrotropin-releasing
hormone, Growth hormonereleasing hormone, Luteinizing hormonereleasing hormone
Anterior Pituitary Regulation: Adrenocorticotropic hormone, Cortisol, Thyroidstimulating hormone, Thyroxine, Triiodothyronine, Growth hormone, Gonadotrophins,
Sex hormones, Insulin-like growth factor, Somatostatin, Prolactin, Endorphins
Posterior Pituitary Regulation: Vasopressin, Oxytocin
Autonomic System : Norepinephrine, Epinephrine, Aldosterone
Renin-Angiotensin System : Insulin, Glucagon, Enkephalins
Corticotrophin-Releasing Hormone (CRH) paraventricular nucleus (PVN)
hypothalamus cytokines TNF-alpha, IL-1,
IL-6 type1 Interferon (IFN-alpha/beta) cytokines
(innate immune response)
(adaptive immune response) IL-2 IFN-gamma

Systemic Response to Injury and Metabolic Support 6

afferent vagal fiber hypothalamus CRH

anterior pituitary gland ACTH zona fasciculate
cortisol stress 3

3 steroid cholesterol Mineralocorticoid,

Glucocorticoid sex steroids1
Cortisol cytosolic receptor glucocorticoid receptor
plasma membrane 4
IL-10 IL-1 antagonist
proinflammatory gene transcription TLR ligation
anti-inflammation
Adrenal insufficiency cortisol aldosterone
steroid
atrophic adrenal gland stress relative adrenal
insufficiency cortisol

gluconeogenesis
renal tubule
basal cortisol cortisol ACTH stimulation test
adrenal insufficiency
adrenal insufficiency low dose
steroid

Systemic Response to Injury and Metabolic Support 7

4 steroid (S) cytoplasmic membrace receptor (R)

heat shock protein (HSP) inactive S R
HSP S-R complex nucleus DNA transcription
anti-inflammation1
Macrophage Inhibitory Factor (MIF) Modulates Cortisol Function
MIF proinflammatory cytokine
, macrophage, T lymphocytes innate
adaptive response anti-inflammation glucocorticoid MIF
acute lung injury MIF
TLR4 macrophage MIF
MIF
The Role of Cathecholamine in Postinjury Inflammation
sympathetic acethylcholine
preganglionic sympathetic fiber adrenal medulla acethylcholine
chromaffin cells epinephrine (EPI) norepinephrine (NE)
3-4
catecholamine


glycogenolysis, gluconeogenesis, lipolysis ketogenesis
adrenergic pancreatic receptor

Systemic Response to Injury and Metabolic Support 8

catecholamine
cytokine EPI TNF-alpha
IL-10 glucocorticoids
IL-12 Th1 cytokine Th1
cytokine Th2 catecholamine
Aldosterone
Aldosterone mineralocorticoid zona glomerulosa
adrenal cortex mineralocorticoid receptor (MR) collecting duct

aldosterone insulin signaling
insulin-sensitizing factors insulin resistance
Aldosterone mononuclear cell monocyte
lymphocyte MR aldosterone
neutrophil MR aldosterone NF-kB

Insulin
peripheral glucose
uptake, hepatic glycogenesis, hepatic glycolysis, lipogenesis protein synthesis
insulin receptor (IR) 2
homodimer heterodimer autophosphorylation intrinsic
tyrosine kinase
insulin resistance
catabolic effect mediator catecholamine, cortisol, glucagon
growth hormone EPI glycogenolysis, lipolysis lactate
stress
insulin resistance acute hyperglycemia
phagocytosis,
chemotaxis adhesion
proinflammatory cytokine NF-kB

tight glycemic control

Systemic Response to Injury and Metabolic Support 9

The Heat Shock Response

stress Heat shock
proteins (HSPs) cytoplasm, nucleus, endoplasmic
reticulum mitrochondria stress

HSPs (protein folding)
bacterial DNA endotoxin stress

proinflammatory response anti-inflammatory response 2

2 Heat shock protein 1

LOCATION

RECOGNIZED AS DAMP?* IMMUNOMODULATORY FUNCTION

- Cytoplasm,
ER
- Function
May act as DAMPs
HSP90 both inside chaperone to activate
and outside innate immune response
the cell
- Function
both inside
and outside
the cell
HSP70 - ER
homolog is
BiP

1.Binds and optimizes RNA polymerase II action to

regulate gene transcription
2.Stabilizes glucocorticoid receptor in the
cytoplasm Important for processing and
membrane expression of TLR Chaperones include
IKK
3.Facilitates antigen presentation to dendritic cells
1.Anti-inflammatory actions when expression is
increased

Exogenous HSP70 elicits

cellular calcium flux, NF-B
2.Inhibits TLR-mediated cytokine production via
activation, cytokine
NF-B Reduces dendritic cell capacity for T-cell
production
stimulation
3.BiP sequesters proteins important to the
unfolded protein response
Exogenous HSP60 inhibits
1.Plays a role in intracellular protein trafficking
HSP60 Mitochondria
Modulates cytokine synthesis
NF-B activation

BiP = binding immunoglobulin protein, DAMP = damage-associated molecular pattern, IKK = IB

kinase; NF-B, nuclear factor-B, TLR = toll-like receptor, ER= endoplasmic reticulum

Systemic Response to Injury and Metabolic Support 10

MEDIATORS OF INFLAMMATION1,2
Cytokines
Cytokines innate adaptive immune response
migration, DNA replication, cell turnover immunocyte
proinflammatory response
anti-inflammatory response
cytokines 3
Tumor Necrosis Factor-alpha (TNF-)

macrophage, dendritic cell, T
lymphocyte
transmembrane TNF
metalloproteinase converting enzyme ADAM-17 TNF- type 1
2 TNF receptor (TNFR1, TNFR2) TNFR1
golgi complex TNFR2 plasma membrane
TNF catabolism, insulin resistance
coagulation, macrophage phagocytosis prostaglandin E2, plateletactivating factor, glucocorticoids eicosanoids
TNF
Interleukin-1
IL-1 11 3 IL-1alpha, IL-1beta, IL-1 receptor antagonist
(IL-1Ra) IL-1alpha, IL-1beta IL-1
receptor type 1(IL-1R1) inflammatory mediator
IL-1alpha epithelium, endothelium platelet
IL-1
IL-1 DAMPs inflammatory mediator
Chemokines Eicosanoids neutrophil
neutrophil
IL-1beta proinflammatory cytokine
monocyte, tissue macrophage dendritic cell
TNF, IL-18 pathogens TNF
IL-1beta

Systemic Response to Injury and Metabolic Support 11

Interleukin-2
IL-2 CD4+T cell, CD8+T cell, NK cell, mast cell dendritic cell
IL-2 CD4+T-cell T helper 1 (Th1) T helper 2 (Th2)
T helper 17 (Th17) T follicular helper (Tfh) IL-2
T regulatory (Treg) cells IL-2 receptors (IL-2R)
10
IL-2
Interleukin-6
DAMPs TLRs IL-6 cytokine
IL-6 60
4-6 10 IL-6
acute phase protein CRP fibrinogen
albumin, cytochrome P450 transferrin
IL-6 B-cell immunoglobulin-producing cell
Th17 Treg Th17 Treg
angiogenesis vascular permeability
IL-6
Interferons (IFN)
Viral replication anti-viral genes
3 1 2
Type I interferons 20 IFN-alpha, IFN-beta IFN-gamma
pathogen DAMPs viral antigen, ds-DNA,
bacteria tumor cell IFN-alpha receptor adaptive immune response
dendritic cell class I major histocompatibility complex
(MHC) IFN-alpha IFN-beta
NK cells chemokine myeloid cells
lymphoid cells IFN/STAT signaling
IFN type 1 inflammasome IL-10
IFN-gamma type 2 IFN T cell, NK cell APC bacterial
antigens, IL-2, IL-12, IL-18 IL-12 IL-18
macrophage phagocytosis oxygen radicals IFNgamma T cell helper T cell subtype 1 B cell
immunoglobulin G

Systemic Response to Injury and Metabolic Support 12

3 cytokine 1
CYTOKINE

TNF

IL-1

SOURCE

COMMENT

Macrophages/monocytes
Kupffer cells, Neutrophils
NK cells, Astrocytes, Endothelial cells,
T lymphocytes, Adrenal cortical cells,
Adipocytes, Keratinocytes, Osteoblasts
Mast cells, Dendritic cells
Macrophages/monocytes
B and T lymphocytes, NK cells,
Endothelial cells, Epithelial cells
Keratinocytes, Fibroblasts, Osteoblasts
Dendritic cells, Astrocytes,
Adrenal cortical cells, Megakaryocytes
Platelets, Neutrophils, Neuronal cells

Among earliest responders after injury; half-life <20 min; activates

TNF receptors 1 and 2; induces significant shock and catabolism

Two forms (IL-1 and IL-1); similar physiologic effects as TNF;

induces fevers through prostaglandin activity in anterior
hypothalamus; promotes -endorphin release from pituitary; halflife <6 min
Promotes lymphocyte proliferation, immunoglobulin production,
gut barrier integrity; half-life <10 min; attenuated production after
major blood loss leads to immunocompromise; regulates
lymphocyte apoptosis

IL-2

T lymphocytes

IL-3

T lymphocytes, Macrophages,
Eosinophils, Mast cells

IL-4

T lymphocytes, Mast cells, Basophils,

Induces B-lymphocyte production of IgG4 and IgE, mediators of
Macrophages, B lymphocytes, Eosinophils, allergic and anthelmintic response; downregulates TNF, IL-1, IL-6,
Stromal cells
IL-8

IL-5

T lymphocytes, Eosinophils,
cells, Basophils

Mast

Promotes eosinophil proliferation and airway inflammation

IL-6

Macrophages, B lymphocytes,
Neutrophils, Basophils, Mast cells,
Fibroblasts, Endothelial cells, Astrocytes,
Synovial cells, Adipocytes, Osteoblasts,
Megakaryocytes, Chromaffin cells,
Keratinocytes

Elicited by virtually all immunogenic cells; long half-life; circulating

levels proportional to injury severity; prolongs activated
neutrophil survival

IL-8

Macrophages/monocytes
T lymphocytes, Basophils, Mast cells
Epithelial cells, Platelets

Chemoattractant for neutrophils, basophils, eosinophils,

lymphocytes

IL-10

T lymphocytes
B lymphocytes Macrophages Basophils
Mast cells Keratinocytes

Prominent anti-inflammatory cytokine; reduces mortality in animal

sepsis and ARDS models

Systemic Response to Injury and Metabolic Support 13

IL-12

Macrophages/monocytes
Neutrophils, Keratinocytes, Dendritic cells, Promotes Th1 differentiation; synergistic activity with IL-2
B lymphocytes

IL-13

T lymphocytes

Promotes B-lymphocyte function; structurally similar to IL-4;

inhibits nitric oxide and endothelial activation

IL-15

Macrophages/monocytes
Epithelial cells

Anti-inflammatory effect; promotes lymphocyte activation;

promotes neutrophil phagocytosis in fungal infections

IL-18

Macrophages
Kupffer cells, Keratinocytes, Adrenal
cortical cells, Osteoblasts

Similar to IL-12 in function; levels elevated in sepsis, particularly

gram-positive infections; high levels found in cardiac deaths

IFN-

T lymphocytes
NK cells, Macrophages

Mediates IL-12 and IL-18 function; half-life of days; found in

wounds 57 d after injury; promotes ARDS

T lymphocytes,
Fibroblasts, Endothelial cells Stromal
cells

Promotes wound healing and inflammation through activation of

leukocytes

T lymphocytes

Preferentially secreted by Th2 cells; structurally similar to IL-2 and

IL-15; activates NK cells, B and T lymphocytes; influences adaptive
immunity

Monocytes/lymphocytes

High mobility group box chromosomal protein; DNA transcription

factor; late (downstream) mediator of inflammation (ARDS, gut
barrier disruption); induces sickness behavior

GM-CSF

IL-21

HMGB1

ARDS = acute respiratory distress syndrome, GM-CSF = granulocyte-macrophage colony-stimulating

factor, IFN = interferon, Ig = immunoglobulin, IL = interleukin, NK = natural killer, Th1 = helper T cell
subtype 1, Th2 = helper T cell subtype 2, TNF = tumor necrosis factor

Eicosanoids
Omega-6 Polyunsaturated Fat Metabolites: Arachidonic Acid
Eicosanoids oxidation phospholipid, arachidonic acid
3 prostaglandins, thromboxanes
leukotrienes phospholipase A2 phospholipids Arachidonic acid cyclooxygenase lipoxygenase
Prostanoids prostaglandins, thromboxanes leukotrienes, lipoxins
5

Systemic Response to Injury and Metabolic Support 14

Eicosanoids
NE, vasopressin, angiotensin II, bradykinin
G-proteincoupled receptor antiinflammation chemotaxis NF-B

5 Arachidonic acid Eicosanoids 3

prostaglandins, thromboxanes leukotrienes 1
neurotransmission vasomotor regulation
prostaglandin E2 (PGE2)
macrophage cAMP
chemokines Treg, myeloid-derived suppressor cells
Prostaglandin (PGI2) Th1 Th2-mediated immune responses
Th17 cytokine
Leukotrienes neutrophil activation, bronchoconstriction vasoconstriction Leukotriene B4 leukotriene receptors
(BLT1) adenylate cyclase cAMP
Lipid droplets (LDs) eukaryotic cell
arachidonic acid TLR signal
LDs Eicosanoids

Systemic Response to Injury and Metabolic Support 15

Eicosanoids
Eicosanoids COX pathway
lipoxygenase pathway
Prostaglandins PGE2 gluconeogenesis lipolysis
2 series Prostaglandins 4 series Leucotrienes
proinflammatory response
Arachidonic acid omega-6
linoleic acid

Omega-3 Polyunsaturated Fat Metabolites

Short chain omega-3 PUFAs linolenic acid
eicosapentaenoic acid (EPA) docosahexaenoic acid (DHA)
long chain omega-3 PUFAs 1.5 - 3.5
EPA DHA COX lipoxygenase (LOX)
Eicosanoids arachidonic acid 6

6 Eicosapentaenoic acid 1
Omega-3 NF-B, TNF, IL-1beta
IL-6, TNF Kupffer cells leukocyte
adhesion migration mediator omega-6
proinflammatory () resolvins Eseries EPA
immunonutrient omega-6
omega-3 PUFAs

Systemic Response to Injury and Metabolic Support 16

omega-3

SURGICAL METABOLISM1.2

resuscitation


Metabolism during Fasting
7
25-35 40
stress

7 70
1800 1
5 4
300-400 75-100

glucose-6-phosphatase
glycogenolysis Glucagon, NE, vasopressin angiotensin II
180 neurons, leukocytes,
erythrocytes renal medulla
Glucagon, EPI cortisol gluconeogenesis EPI

Systemic Response to Injury and Metabolic Support 17

cortisol pyruvate gluconeogenesis

lactate, glycerol amino acids alanine glutamine lactate
glycolysis
4 A.
B. 1
MASS
(kg)

ENERGY
(Kcal)

DAYS AVAILABLE

Water and
minerals

49

Protein

24,000

13

Glycogen

0.2

800

0.4

Fat

15

140,000

78

Total

70.2

164,800

91.4

RQ

Kcal/g

DAILY
REQUIREMENT

A. COMPONENT

B. SUBSTRATE

O2 CONSUMED CO2 PRODUCED

(L/g)
(L/g)

Glucose

0.75

0.75

7.2 g/kg per day

Dextrose

3.4

Lipid

1.4

0.7

1.0 g/kg per day

Protein

0.8

0.8

0.8 g/kg per day

RQ = respiratory quotient
A = Body fuel reserves in a 70-kg man and

B = Energy equivalent of substrate oxidation

lactate pyruvate gluconeogenesis Cori

cycle 40 8
lactate
75 70

Systemic Response to Injury and Metabolic Support 18

hepatic gluconeogenesis
cortisol
solid organ

8 hepatic gluconeogenesis Cori cycle lactate pyruvate1

20
2-5
ketone bodies
9

9 70
proteolysis ketone
gluconeogenesis1

Systemic Response to Injury and Metabolic Support 19

deamination () gluconeogenesis
gluconeogenesis glutamine glutamate
adipose tissue 40
triglyceride
glycerol 160 adipose tissue glucagon
catecholamine
ketone bodies
glycolysis, gluconeogenesis proteolysis
RQ

Metabolism after Injury

1 0 11

1 0
RBC = red blood cell, WBC = white blood cell 1
Lipid Metabolism after Injury
stress

(adipose tissue) 50-80
(lipolysis) cathecholamine triglyceride lipase
lipolysis ACTH, thyroid hormone, cortisol, glucagon, GH

Systemic Response to Injury and Metabolic Support 20

11 1
Lipid Absorption
Adipose tissue
glycerol 1 9
triglyceride triglyceride
lipase
duodenum triglycerides
monoglycerides triglycerides
esterification acyl coenzyme A (acyl-CoA) 12

12 triglycerides lipase monoglycerides fatty

acids Triglycerides chylomicrons
1

Systemic Response to Injury and Metabolic Support 21

Long-chain triglycerides (LCTs) 12

esterification chylomicrons
portal circulation albumin
Hepatocytes stress
phospholipids triglycerides very-low-density lipoproteins
chylomicrons, triglycerides
lipoprotein lipase TNF
Lipolysis and Fatty Acid Oxidation
Adipose tissue triglyceride lipase glycerol

albumin glycerol
glycerokinase glycerol-3-phosphate
esterification triglyceride
gluconeogenesis
glycerokinase Glycerol 13

13 adipose tissue triglyceride lipase cAMP

pathway 1
acyl- CoA cytoplasm carnitine
fatty acyl-CoA mitochondria 14
beta oxidation acetyl-CoA tricaboxylic cycle
12 ATP, acetyl-CoA ketogenesis

Systemic Response to Injury and Metabolic Support 22

14 fatty acyl-CoA mitochondria

carnitine beta-oxidation acetyl-CoA 1
Medium-chain triglycerides (MCTs) 6-12
mitochondrial membrane carnitine MCTs
LCTs MCTs

respiratory quotient (RQ)=0.7 RQ=1

Ketogenesis
TCA cycle
Acetyl-CoA ketogenesis
ketone ketone
ketosis
ketogenesis
ketogenesis

Systemic Response to Injury and Metabolic Support 23

Carbohydrate Metabolism

disaccharide sucrase, lactase maltase
glucose galactose
active transport sodium pump fluctose
() 1 4
(dextrose) 3.4
()

50 TCA cycle ketosis

gluconeogenesis stress proinflammatory
mediator

glucose-6-phosphate
glycogenesis glycogenolysis pyruvate
lactate (pyruvic acid pathway) 15
RQs >1.0 glucosuria, thermogenesis

hepatic gluconeogenic
Glucagon alanine glutamine

glucose intolerance
pyruvate dehydrogenase activity
pyruvate acetyl-CoA TCA cycle
Protein and Amino Acid Metabolism
80-120 1 4
glucocorticoids
30 1.5
10 15

Systemic Response to Injury and Metabolic Support 24

15 pentose monophosphate pathway Glucose-6phosphate 1

gluconeogenesis
acute-phase proteins 16
negative nitrogen balance urine nitrogen
7 3-7

16
1

Systemic Response to Injury and Metabolic Support 25

Nutrition in the Surgical Patient

Nutrition in the surgical patient
catabolic effect

Estimation of Energy Requirements

1. (Clinical assessment)
-

-


-

-
- (total gastrectomy)

- Subjective Global Assessment (SGA)

17
2. (Anthropometric assessment)
skinfold, Glycogen
percentile 5
3. (Biochemical and laboratory assessment)
- Albumin level: acute phase protein
albumin 21

albumin albumin

- prealbumin level albumin 24-48

prealbumin

- transferrin level visceral protein

8 albumin
4. (Functional assessment)

Systemic Response to Injury and Metabolic Support 26

17 subject global assessment 2

5. (Basal energy expenditure)
Harris-Benedict equations
BEE (men) = 66.47 + 13.75 (W) + 5.0 (H) 6.76 (A) kcal/d
BEE (women) = 655.1 + 9.56 (W) +1.85 (H) 4.68 (A) kcal/d
W=(), H=(), A=()
stress factor fever factor 5

Systemic Response to Injury and Metabolic Support 27

5 Stress Burn1
Adjustment
Protein(g)/kg/Day
above BEE

Condition

Kcal/Kg/DAy

Normal/moderate
malnutrition

2530

1.1

150:1

Mild stress

2530

1.2

1.2

150:1

30

1.4

1.5

120:1

Severe stress

3035

1.6

90120:1

Burns

3540

2.5

90100:1

Moderate stress

NPC:N

BEE = Basal Energy Expenditure

NPC:N = Non-Protein calories : Nitrogen
30 Kcal/kg/d stress
stress trauma sepsis non
protein calories 1.2-2

(Protein requirement)
1
1.2-1.5
urea nitrogen
encephalopathy
(Fat requirement)
1530 1 9
osmolarity

Systemic Response to Injury and Metabolic Support 28

(Carbohydrate requirement)
50-70
(polysaccharide) (disaccharide)
Hydrolysis (monosaccharide)
osmolarity

non protein calories : nitrogen ratio 150 1 (1
= 6.25 )
80 1 100 1 0.25-0.35

12

Overfeeding

actual body weight BEE
indirect calorimetry BEE 10-15 stress
(dry weight)

Overfeeding

Enteral Nutrition

mucosal atrophy bacterial translocation
early enteral nutrition
parenteral nutrition acute phase protein

Systemic Response to Injury and Metabolic Support 29

systematic review (anastomosis leakage)

prospective randomized control trials albumin

4 / enteral nutrition
24-48
Meta-analysis 44

early enteral feeding
resuscitation
bowel sound

jejunum gastric feeding
gastroparesis aspiration gastroparesis
gastric residual 200 4-6 abdominal distension

low output enterocutaneous fistula

enteral feeding fistula open abdomen
fistula
Hypocaloric Enteral Nutrition

(Resting Energy Expenditure; REE)

25-30 kcal/kg
lean body mass

mitochondrial free radical, plasma membrane redox system insulin sensitivity
single center, RCTs permissive underfeeding
target enteral feeding 60-70
90-100 permissive underfeeding
guideline hypocaloric feeding

Systemic Response to Injury and Metabolic Support 30

Enteral Formulas

organ dysfunction
complex solution GI tolerance-promoting, anti-inflammatory, immunemodulating feeding tolerance peptide Medium chain triglyceridebased formulas prebiotics feeding tolerance
Short bowel syndrome, inflammatory bowel disease
hydrolyzed protein formulas
stress sterile inflammatory response
immune modulating nutrients immunonutrition
Glutamine Arginine PUFAs
Glutamine 2 3
75 glutamine nonessential amino acid
stress sepsis
glutamine
Glutamine nitrogen balance
glutamine nucleotide
enterocyte immunocyte lymphocyte macrophage
Glutathione
REDOX study Glumatine multiorgan
failure glutamine burn trauma

Arginine nonessential amino acid

(wound healing) nitrogen balance

Canadian Clinical Practice Guidelines arginine

Omega 3 PUFAs (fish oil) 6 pro inflammatory response prostaglandin omega 6 : omega 3

EDEN-Omega study omega 3 fatty acid, linolenic acid

Systemic Response to Injury and Metabolic Support 31

anti-oxidants ventilator-free days acute lung injury

Low-Residue Isotonic Formulas,
Isotonic Formulas with Fiber, Immune-Enhancing Formulas, Calorie-Dense Formulas, HighProtein Formulas, Elemental Formulas, Renal Failure Formulas, Pulmonary Failure
Formulas, Hepatic Failure Formulas
Low-Residue Isotonic Formulas
1 Kcal/ml 1500-1800 ml

nonprotein-calorie:nitrogen 150:1
Isotonic Formulas with Fiber
lipase
short-chain fatty acids (SCFAs)
colonocytes SCFA receptor expression
colonic microbiome
Immune-Enhancing Formulas Glutamine, Arginine, omega 3 fatty
acid nucleotides

Calorie-Dense Formulas 1.5-2 kcal/mL

osmolality NG tube
gastrostomy tube
High Protein Formulas
Non-Protein-Calories: Nitrogen ratio 80:1 120:1 observational
studies RCTs

Elemental Formulas small peptides

Medium-Chain Triglycerides (MCTs) Long-Chain Triglycerides (LCTs)
osmolarity
malabsortion
pancreatitis
Renal failure Formulas
potassium, phosphorus, magnesium essential amino
acid Non-Protein Calories: Nitrogen

Systemic Response to Injury and Metabolic Support 32

Pulmonary failure Formulas 50

Hepatic Failure Formulas branched-chain amino

acids leucine, isoleucine valine aromatic amino acid
Branch-chain amino acid (BCAA) hepatic encephalopathy
end-stage liver disease protein energy
malnutrition

Access for Enteral Nutritional Support

6
6 enteral feeding1
ACCESS OPTION

COMMENTS

Nasogastric tube

Short-term use only; aspiration risks; nasopharyngeal trauma; frequent dislodgment

Nasoduodenal/nasojejunal
tube

Short-term use; lower aspiration risks in jejunum; placement challenges (radiographic

assistance often necessary)
Endoscopy skills required; may be used for gastric decompression or bolus feeds;
aspiration risks; slightly higher complication rates with placement and site leaks

Percutaneous endoscopic
gastrostomy (PEG)
Surgical gastrostomy

Requires general anesthesia and small laparotomy; procedure may allow placement of
extended duodenal/jejunal feeding ports; laparoscopic placement possible

Fluoroscopic gastrostomy

Blind placement using needle and T-prongs to anchor to stomach; can thread smaller
catheter through gastrostomy into duodenum/jejunum under fluoroscopy

PEG-jejunal tube

Jejunal placement with regular endoscope is operator dependent; jejunal tube often
dislodges retrograde; two-stage procedure with PEG placement, followed by
fluoroscopic conversion with jejunal feeding tube through PEG

Direct percutaneous
endoscopic jejunostomy
(DPEJ)
Surgical jejunostomy
Fluoroscopic jejunostomy

Direct endoscopic tube placement with enteroscope; placement challenges; greater

injury risks
Commonly carried out during laparotomy; general anesthesia; laparoscopic placement
usually requires assistant to thread catheter; laparoscopy offers direct visualization of
catheter placement
Difficult approach with injury risks; not commonly done

Systemic Response to Injury and Metabolic Support 33

Nasogastric tube aspiration

laryngeal reflex
: NG tube blind technique
Xrays 30
percutenous
:
Nasojejunal feeding pulmonary complications pneumonia 20
NG tube feeding tolerance gastroparesis
: prokinetic agent, right
lateral decubitus, gastric insufflation 20
Fluoroscopy-guided intubation endoscopy-guided placement
90 30 percutenous
:
Percutaneous Endoscopic Gastrostomy (PEG)

18-28 Fr.
:
guidewire snare
guidewire guidewire gastrostomy
wire
24
: ascites, coagulopathy, gastric varices,
3 , , ,
enteric fistula,
Percutaneous Endoscopic Gastrostomy-Jejunostomy (PEG-J) gastric
feeding intolerance
: guidewire PEG pylorus endoscopy
Fluoroscopy guidewire ligament of Treitz
:

Systemic Response to Injury and Metabolic Support 34

Direct percutaneous endoscopic jejunostomy (DPEJ) tube

PEG-J PEG-J
: PEG enteroscope
colonoscope jejunum
Surgical Gastrostomy and Jejunostomy
Foley catheter 24-48
: gastrostomy bolus
reservoir feeding intolerance
jejunostomy diarrhea
jejunostomy 2-3 gastrostomy
jejunostomy 4
wire guide fluoroscopy mucosa

(Parenteral Nutrition)
osmolarity



positive nitrogen
balance



meta-analysis

7 enteral nutrition
Blunt Penetrating
7
stress hormone

Systemic Response to Injury and Metabolic Support 35

7 1
BLUNT TRAUMA
COMPLICATION
Abdominal abscess
Pneumonia
Wound infection
Bacteremia
Urinary tract
Other
Total

PENETRATING TRAUMA

EN=48 PN = 44 EN = 38
2
1
2
4
10
1
0
2
3
1
4
0
1
1
0
5
4
1
13
22
7

% Complications
27% 50% 18%
EN = Enteral Nutrition, PN = Parenteral Nutrition

PN = 48
6
2
1
1
1
1
12

30%

TOTAL
EN=44 PN= 84
4
7
5
12
3
3
1
5
1
2
6
5
20
34

23%

39%

1. TE fistula, gastroschisis,
omphalocele massive intestinal atresia
short bowel syndrome, enzyme deficiency, meconium ileus
idiopathic diarrhea
2. short-bowel syndrome ( 100
IC valve 50
IC valve )
3. enteroenteric, enterocolic, enterovesical high-output
enterocutaneous fistulas ( 500 )
4. prolonged paralytic ileus ( 7-10),
open abdominal trauma
5.
6. cachexia
7. enteral feeding tube
5 enteral nutrition

Systemic Response to Injury and Metabolic Support 36

1.
2.
3.
osmolarity

Total Parenteral Nutrition (TPN) central parenteral nutrition

dextrose 15-25 central

venous catheter subclavian vein internal jugular vein superior
vena cava TPN Port
A
Peripheral Parenteral Nutrition (PPN)
dextrose
5-10
TPN
2

2-3
nitrogen balance
- 2-3
CBC, BUN, LFT, phosphate Magnesium

(DTX) 6 serum
glucose hyperglycemia glycosuria
Dextrose

hypokalemia
potassium positive
nitrogen balance 240 mEq hypokalemia

Systemic Response to Injury and Metabolic Support 37

Glycosuria potassium
potassium hypokalemia (
hyperkalemia )

10-15
20% lipid emulsion 500 1-3

24
Reticuloendothelial cells
(RE cells)

Homeostasis local systemic response
complex pathways

early enteral feeding
parenteral feeding

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United States of America, McGraw-Hill Education. 2015;13-64.
2. Townsend C, Beauchamp R, Evers B, et al. Sabiston Textbook of Surgery Edition
19. Canada, Elsevier Saunders. 2012;120-50.
3. Rojratsirikul C, Sangkhathat S, Patrapinyokul S. Application of Subjective Global
Assessment as a screening tool for malnutrition in Pediatric Surgical Patients. J
med Assoc Thai. 2004;87(8):939-46.