Far

Eastern University – Nicanor Reyes Medical Foundation o respirations

BASIC SURGERY A: SYSTEMIC RESPONSE TO INJURY AND METABOLIC SUPPORT o WBC
Dr. Naui, MD - are similar to those observed with infection

OBJECTIVES
At the end of the session, learners should be able to discuss
- central nervous system regulation of injury
- cellular stress response
- mediators of inflammation
- cellular response to injury
- cell mediated inflammatory response
- endothelium mediated injury
- surgical metabolism

INTRODUCTION
- Inflammatory response to injury
o to restore tissue function
o Eradicate invading microorganisms
- Local- limited duration, restores function
- Major
o overwhelming inflammatory response
o Potential multi-organ failure

o Adversely impacts patient survival CNS REGULATION OF INFLAMMATION IN RESPONSE TO INJURY
- The brain follows with a hormone release (ACTH, gluco) into
The immune system has developed to respond to neutralize the systemic circulation and by sympathetic response
pathogenic microorganism as well as coordinate tissue repair - Vagal – induces acetylcholine directed at injury to curtail the
inflammatory response
Trauma is the leading cause of mortality and morbidity

DETECTION OF CELLULAR INJURY
- Injury activates the innate immune system to produce a
systemic inflammatory response in an attempt to limit
damage and to restore homeostasis

- The central nervous system (CNS) communicates with the
body through ordered systems of sensory and motor
neurons, which receive and integrate information to
generate a coordinated response.
- Schematic representation of the systemic inflammatory
o Rather than being an immune-privileged organ, recent
response syndrome (SIRS) after injury, followed by a period
work indicates that the CNS receives information with
of convalescence mediated by the counterregulatory anti-
regard to injury-induced inflammation both via soluble
inflammatory response syndrome (CARS).
mediators as well as direct neural projections that
- Severe inflammation may lead to acute multiple organ failure
transmit information to regulatory areas in the brain
(MOF) and early death after injury (dark blue arrow).

- A lesser inflammatory response followed by excessive CARS
SIGNALING
may induce a prolonged immunosuppressed state that can
- Humoral
also be deleterious to the host (light blue arrow).
o inflammatory mediators in the circulation can induce
- Normal recovery after injury requires a period of systemic
fever and anorexia
(i.e. TNF-α). 

inflammation followed by a return to homeostasis
- Neural

o parasympathetic vagal stimulation attenuates the
DETECTION OF CELLULAR INJURY
inflammatory response via Ach release
- The clinical features of the injury-mediated SIR, characterized
§ Reduces HR, increases gut motility, dilates
by INCREASED:
arterioles, constricts pupils, and decreases
o heart rate
inflammation.
o body temp

§ Reduces macrophage activation

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 § Reduces macrophage release of pro-inflammatory Cortisol is a glucocorticoid steroid hormone released by the
mediators (TNF-α, IL-1, IL-18) adrenal cortex in response to ACTH.

HORMONE SIGNALING Cortisol release is increased during times of stress and may be
- Hormone classifications chronically elevated in certain disease processes.
o polypeptide (cytokine, insulin) - For example, burn-injured patients may exhibit elevated
o amino acid (epinephrine, serotonin, or histamine) levels for 4 weeks.
o fatty acid (cortisol, leukotrienes)
- Pathways Metabolically, cortisol potentiates the actions of glucagon and
o Receptor Kinases – insulin epinephrine that manifest as hyperglycemia.
o Guanine nucleotide binding (G-protein) - prostaglandins
o Ligand Gated ion channels Cortisol acts on liver enzymes by decreasing glycogenesis, while
increasing gluconeogenesis.
Hormones are chemical signals that are released to modulate the
function of target cells. In skeletal muscle, cortisol facilitates the breakdown of protein
and amino acids, and mediates the release of lactate.
Hormone receptors are present on or within the target cells and
allow signal transduction to progress intracellularly mostly Subsequently, these substrates are used by the liver for
through three major pathways gluconeogenesis.

ADRENOCORTICOTROPIC HORMONE In adipose tissue cortisol stimulates the release of free fatty
- Synthesized anterior pituitary acids, triglycerides, and glycerol to increase circulating energy
- Regulated by circadian signals stores.
- Pattern is dramatically altered in injured patients
- Elevation is proportional to injury severity Wound healing also is impaired, because cortisol reduces
- Released by: pain, anxiety, vasopressin, angiotensin II, transforming growth factor beta (TGF- ) and insulin-like growth
cholecystokinin, catecholamines, and pro-inflammatory factor I (IGF-I) in the wound.
cytokines
This effect can be partially ameliorated by the administration of
Adrenocorticotropic hormone (ACTH) is a polypeptide hormone vitamin A.
released by the anterior pituitary gland.
EXOGENOUS ADMINISTRATION
ACTH binds with receptors in the zona fasciculata of the adrenal - Adrenal suppression in the acutely ill
gland, which mediate intracellular signaling and subsequent o Acute Adrenal Insufficiency
cortisol release. o Atrophy of the adrenal glands
o Weakness, n/v, fever, hypotension
ACTH release follows circadian rhythms in healthy humans; o Hypoglycemia, hyponatremia, hyperkalemia
however, during times of stress this diurnal pattern becomes - Immunosuppression
blunted because ACTH release is elevated in proportion to the o Thymic involution, decreased T-killer and NK fcn, graft vs
severity of injury. host rxns, delayed hypersensitivity responses, inability
of monocyte intracellular killing, inhibition of
Several important stimuli for ACTH release are present in the superoxide reactivity and chemotaxis in neutrophils
injured patient, including corticotropin-releasing hormone, pain, o Down regulates pro-inflammatory cytokine production
anxiety, vasopressin, angiotensin II, cholecystokinin, vasoactive (TNF-α, IL-1, IL-6)
intestinal polypeptide, catecholamines, and proinflammatory o Increases anti-inflammatory mediator IL-10
cytokines. o Useful in septic shock, surgical trauma, and CABG

Within the zona fasciculata of the adrenal gland, ACTH signaling MACROPHAGE INHIBITORY FACTOR
activates intracellular pathways that lead to glucocorticoid - Glucocorticoid antagonist
production Conditions of excess ACTH stimulation result in - produced by anterior pituitary & T-lymphocytes
adrenocortical hypertrophy - Reverses immunosuppressive effects of glucocorticoids
- Potentiates G- and G+ septic shock
GLUCOCORTICOIDS - Experimentally improves survival
- Cortisol – elevated following injury,
o duration of elevation depends on severity of injury Macrophage migration–inhibiting factor (MIF) is a
- Potentiates hyperglycemia neurohormone that is stored and secreted by the anterior
o Hepatic gluconeogenesis pituitary and by intracellular pools within macrophages.
o Muscle and adipose tissue àinduces insulin resistance
o Skeletal muscle àprotein degradation, lactate release MIF is a counterregulatory mediator that potentially reverses the
o Adipose à reduces release of TG, FFA, glycerol anti-inflammatory effects of cortisol.
- During times of stress, hypercortisolemia, and host
immunosuppression, MIF may modulate the inflammatory

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 response by inhibiting the immunosuppressive effect of glomerulosa
cortisol on immunocytes and thereby increasing their - Maintains intravascular volume
activity against foreign pathogens. o Conserves sodium
o Eliminates potassium and hydrogen ions
GROWTH HORMONE - Acts on the early distal convoluted tubules
- During stress à protein synth, fat mobilization, and skeletal - Deficiency- hypotension, hyperkalemia
cartilage growth - Excess- edema, HTN, hypokalemia, metab alkalosis
- GH admin to pediatric burn patients shows improvement in
their clinical course Aldosterone is a mineralocorticoid released by the zona
glomerulosa of the adrenal cortex.
Growth hormone (GH) is a neurohormone expressed primarily by
the pituitary gland that has both metabolic and Aldosterone increases intravascular volume by acting on the
immunomodulatory effects. renal mineralocorticoid receptor of the distal convoluted tubules
to retain sodium and eliminate potassium and hydrogen ions.
GH promotes protein synthesis and insulin resistance, and
enhances the mobilization of fat stores GH primarily exerts its Aldosterone secretion is stimulated by ACTH, angiotensin II,
downstream effects through direct interaction with GH receptors decreased intravascular volume, and hyperkalemia.
and secondarily through the enhanced hepatic synthesis of IGF-I.
Aldosterone deficiency is manifested by hypotension and
IGF circulates primarily bound to various IGF-binding proteins and hyperkalemia, whereas aldosterone excess is manifested by
also has anabolic effects, including increased protein synthesis edema, hypertension, hypokalemia, and metabolic alkalosis.
and lipogenesis
INSULIN
Critical illness is associated with an acquired GH resistance and - Stress inhibited release + peripheral insulin resistance =
contributes to decreased levels of IGF. hyperglycemia
- Injury has 2 phases of insulin release
This effect in part mediates the overall catabolic phenotype o Within hours- release is suppressed
manifested during critical illness. o Later- normal/xs insulin production with peripheral
insulin resistance
In addition, GH enhances phagocytic activity of immunocytes - Hyperglycemia during critical illness has immunosuppressive
through increased lysosomal superoxide production effects
- Insulin treatment of elevated glucose levels esp. in diabetics
CATECHOLAMINES reduces mortality after injury
- Severe injury activates the adrenergic system
- Norepi and Epi immediately increase 3-4 fold and remain Hyperglycemia and insulin resistance are hallmarks of critical
elevated 24-48hrs after injury illness due to the catabolic effects of circulating mediators,
- Epinephrine including catecholamines, cortisol, glucagon, and growth
o hepatic glycogenolysis, gluconeogenesis, lipolysis, and hormone
ketogenesis
o Decreases insulin and glucagon secretion Hyperglycemia during critical illness has immunosuppressive
o Peripheral- lipolysis, insulin resistance in skeletal m. effects, including glycosylation of immunoglobulins and
o = stress induced hyperglycemia decreased phagocytosis and respiratory burst of monocytes, and
thus is associated with an increased risk for infection
Catecholamines are hormones secreted by the chromaffin cells
of the adrenal medulla and function as neurotransmitters in the ACUTE PHASE PROTEINS
CNS. - Nonspecific markers
- Response to injury, infection, inflammation
The most common catecholamines are epinephrine, - C-reactive protein best reflects inflammation
norepinephrine, and dopamine, which have metabolic, o No diurnal variation, not affected by feeding 

immunomodulatory, and vasoactive effects. o Affected only by preexisting hepatic failure
o Accuracy surpasses that of ESR 

After severe injury, plasma catecholamine levels are increased
threefold to fourfold, with elevations lasting 24 to 48 hours INFLAMMATORY MEDIATORS
before returning toward baseline levels. - Heat Shock Proteins
- Reactive Oxygen Metabolites
EPINEPHRINE – OTHER EFFECTS - Eicosanoids
- Increase secretion of T3, T4, and renin - Fatty Acid Metabolites
- Reduces release of aldosterone - Kallikrein-Kinin System
- Enhances leukocyte demargination and lymphocytosis - Serotonin
- Histamine
ALDOSTERONE - Cytokines
- Synthesized, stored, released from the adrenal zona

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 Cytokines are a class of protein signaling compounds that are Eicosanoids are derived primarily by oxidation of the membrane
essential for both innate and adaptive immune responses. phospholipid arachidonic acid (eicosatetraenoic acid) and are
composed of subgroups, including prostaglandins, prostacyclins,
Cytokines mediate a broad sequence of cellular responses, hydroxyeicosatetraenoic acids (HETEs), thromboxanes, and
including cell migration, DNA replication, cell turnover, and leukotrienes.
immunocyte proliferation
The synthesis of arachidonic acid from phospholipids requires
When functioning locally at the site of injury and infection, the enzymatic activation of phospholipase A2 (Fig. 2-5). Products
cytokines mediate the eradication of invading micro-organisms of the COX pathway include all of the prostaglandins and
and also promote wound healing. thromboxanes.

However, an exaggerated proinflammatory cytokine response to The lipoxygenase pathway generates leukotrienes and HETE
inflammatory stimuli may result in hemodynamic instability and
metabolic derangements

HEAT SHOCK PROTEINS
- Induced by hypoxia, trauma, heavy metals, and hemorrhage
- Presumed to protect cells from the deleterious effects of
traumatic stress
- Production seems to decline with age

Heat shock proteins (HSPs) are a group of intracellular proteins
that are increasingly expressed during times of stress, such as
burn injury, inflammation, and infection

REACTIVE OXYGEN METABOLITES
- Short-lived
- Cause tissue injury by oxidation of unsaturated fatty acids

within cell membranes
EICOSANOID EFFECTS
- Produced by anaerobic glucose oxidation and reduction to
- Pancreas – glucagon secretion- PGD2, PGE2
superoxide anion in leukocytes
- Liver – glucagon stimulated glucose production- PGE2
- Further metabolized to hydrogen peroxide and hydroxyl
- Adipose – lipolysis- PGE2
radicals
- Bone – resorption- PGE2, PGF2α, PGI2
- Cells are protected by oxygen scavengers – glutathione and
- Parathyroid – PTH secretion- PGE2
catalases
- Pulmonary – Bronchoconstriction- PGF2α, TXA2, LTC4, LTD4,
- In ischemia- production of oxygen metabolites are activated
LTE4
but nonfunctional due to no oxygen supply. After
- Immune – suppress lymphocytes- PGE2
reperfusion, large amounts are produced causing injury
- Hematologic

o platelet aggregation- TXA2
Reactive oxygen species (ROS) are small molecules that are
o Capillary leakage- PGE2, LT
highly reactive due to the presence of unpaired outer orbit
o PMN adherence and activation- LT
electrons.
- Pituitary

o Prolactin- PGE1
They can cause cellular injury to both host cells and invading
o LH- PGE1, PGE2, 5-HETE
pathogens through the oxidation of unsaturated fatty acids
o TSH- PGA1, PGB1, PGE1, PGE1α
within cell membranes.
o GH- PGE1

- Renal – renin secretion- PGE2, PGI2
Oxygen radicals are produced as a by-product of oxygen
- GI – cytoprotective- PGE2
metabolism as well as by anaerobic processes. Potent oxygen

radicals include oxygen, superoxide, hydrogen peroxide, and
FATTY ACID METABOLITES
hydroxyl radicals.
- Omega 6 FA – precursors of inflammatory mediators (LT, PG,

platelet activating factor)
EICOSANOIDS
o found in enteral nutrition formulas
- Secreted by nucleated cells (not lymphocytes)
- Substituting Omega 3 FA attenuate the inflammatory
- Generated rapidly by hypoxic injury, direct tissue injury,
response
endotoxin, norepinephrine, vasopressin, ang II, bradykinin,
o Reduces the metabolic rate, normalizes glucose
serotonin, ACh, cytokines, histamine
metabolism, attenuates weight loss, improves nitrogen
- Adverse effects include acute lung injury, pancreatitis, renal
balance, reduces endotoxin induced acute lung injury,
failure
minimizes reperfusion injury to the myocardium, small
- NSAIDs acetylate COX which reduce prostaglandin levels
intestine, and skeletal muscles.

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 KALLIKREIN-KININ SYSTEM Cytokines are a class of protein signaling compounds that are
- Bradykinins are potent vasodilators essential for both innate and adaptive immune responses.
- Stimulated by hypoxic and ischemic injury
o Hemorrhage, sepsis, endotoxemia, tissue injury Cytokines mediate a broad sequence of cellular responses,
o Magnitude proportional to severity of injury Including cell migration, DNA replication, cell turnover,
- Kinins increase capillary permeability (edema), pain, inhibit and immunocyte proliferation
gluconeogenesis, renal vasodilation, increase
bronchoconstriction TUMOR NECROSIS FACTOR α
- In clinical trials, bradykinin antagonists help reverse G- sepsis, - Synthesized from monocytes, macrophages, Tcells
but do not improve survival - Responds early, T ½ < 20min
- Potent evocation of cytokine cascade
The kallikrein-kinin system is a group of proteins that contribute - Induces muscle catabolism/cachexia, coagulation, PGE2, PAF,
to inflammation, blood pressurecontrol, coagulation, and pain glucocorticoids, eicosanoids
responses - Circulating TNF receptors compete with cellular receptors
and may act as a counter regulatory system to prevent
Bradykinin and kallikrein levels are increased during gram- excessive TNF-α activity
negative bacteremia,hypotension, hemorrhage, endotoxemia,
and tissue injury. Tumor necrosis factor alpha (TNF) is a cytokine that is rapidly
mobilized in response to stressors such as injury and infection,
SEROTONIN and is a potent mediator of the subsequent inflammatory
- Present in intestinal chromaffin cells & platelets response.
- Vasoconstriction, bronchoconstriction, platelet aggregation
- Myocardial chronotrope and ionotrope INTERLEUKIN-1-18
- Unclear role in inflammation IL-1
- Two forms IL-1α and IL-1 β
Serotonin is a monoamine neurotransmitter (5- - Induces fever through prostaglandin activity
hydroxytryptamine) derived from tryptophan - Promotes β-endorphin release
IL-2

This neurotransmitter stimulates vasoconstriction, - Promotes lymphocyte proliferation
bronchoconstriction, and platelet aggregation. - Immunoglobulin production

- Gut barrier integrity
Serotonin also increases cardiac inotropy and chronotropy IL-3
through nonadrenergic cyclic adenosine monophosphate (cAMP) IL-4
pathways - Induces B-lymphocyte production of IgG4 and IgGE
- Mediators of allergic and anthelmic response
HISTAMINE IL-5
- Stored in neurons, skin, gastric mucosa, mast cells, basophils, - Promotes eosinophil proliferation
and platelets - Airway inflammation
- H1 – bronchoconstriction, increases intestinal motility and IL-6
myocardial contractility - Elicited by virtually all immunogenic cells o Prolongs
- H2 – inhibits histamine release activated neutrophil survival

Histamine is synthesized by the decarboxylation of the amino Interleukin-1 (IL-1) is represented by two active subtypes
acid histidine There are four histamine receptor (H) subtypes with
varying physiologic roles INTERFERON-y
- Detectable in circulation by 6 hrs and remain elevated for up
COMPLEMENT to 8 days
- Immediate activation following injury - Activate circulating and tissue macrophages
- Major mechanism of innate immune system - Induces acute lung inflammation by activating alveolar
- Eliminates immune complexes as well as damaged and dead macrophages after surgery or trauma
cells
GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR
CYTOKINE RESPONSE TO INJURY - Delays apoptosis of macrophages and PMNs
CYTOKINES - Promotes the maturation and recruitment of PMNs in
- Most potent mediators of inflammation inflammation and perhaps wound healing
- Local- eradicate microorganisms, promote wound healing - May contribute to organ injury such as ARDS
- Overwhelming response- hemodynamic instability (septic - Peri-operative GM-CSF undergoing major oncologic
shock) or metabolic derangements (muscle wasting) procedures and burn patients demonstrate enhances
- Uncontrolled- end-organ failure, death neutrophil counts and function
- Self-regulatory production of anti-inflammatory cytokines,
but inappropriate release may render the patient GM-CSF, IL-3, and IL-5 compose a small family of cytokines that
immunocompromised and susceptible to infection regulate the growth and activation of immune cells.

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 CELL MEDIATED INFLAMMATION
Mass Energy Days
- Platelets
(kg) (Kcal) Available
o Source of eicosanoids and vasoactive mediators
o Clot is a chemoattractant for PMNs/monocytes Water 49 0 0
o Modulate PMN endothelium adherence
o Migration occurs within 3 hrs of injury Protein 6 24,000 13
§ Mediated by serotonin, PAF, PGE2
- Eosinophils Glycogen 0.2 800 0.4
o Migrate to parasitic infection and allergen challenge to
Fat 15 140,000 78
release cytotoxic granules
o Reside in the GI, lung, and GU tissues Total 70.2 164,800 91.4
o Activated by IL-3, GM-CSF, IL-5, PAF, and anaphylatoxins
C3a and C5a - A healthy 70kg adult will use 180 g /d of glucose to support
- Lymphocytes obligate glycolytic cells (neurons, RBCs, PMNs, renal medulla,
o T-helpers produce IL-3, TNF-α, GM-CSF skeletal m.)
§ TH1: IFN-γ, IL-2, IL-12 - Glucagon, Norepi, vasopressin, AngII promote utilization of
§ TH2: IL-4, IL-5, IL-6, IL-9, IL-10, IL-13 glycogen stores during fasting
§ Severe infection – shift toward more TH2 - Glucagon, Epi, and cortisol promote gluconeogenesis
- Mast Cells - Precursors include lactate (sk.m., rbc, pmn), glycerol, and aa
o First responders to injury (ala, glutamine)
o Produce histamine, cytokines, eicosanoids, proteases,
chemokines, TNF-α (stored in granules) METABOLISM OF SIMPLE STARVATION
o Cause vasodilation, capillary leakage, recruit - Lactate is not sufficient for glucose demands
immunocytes - Protein must be degraded (75 g/d) for hepatic
- Monocytes gluconeogenesis
o Downregulation of receptor TNFR is clinically and - Proteolysis from decreased insulin and increased cortisol
experimentally correlated with CHF, nonsurvival in - Elevated urinary nitrogen (7 -> 30 g/d)
sepsis
- Neutrophils Lactate production from skeletal muscle is insufficient to
o Modulate acute inflammation maintain systemic glucose needs during short-term fasting
o Adhesion/transmigration – ICAM 1, 2, PECAM 1, VCAM (simple starvation).
1, CD18
Therefore, significant amounts of protein must be degraded daily
ENDOTHELIUM-MEDIATED INJURY (75 g/d for a 70-kg adult) to provide the amino acid substrate for
- Neutrophil-Endothelium Interaction hepatic gluconeogenesis.
o Increased vascular permeability – facilitate oxygen
delivery and immunocyte migration Proteolysis during starvation, which results primarily from
o Accumulation of neutrophils at injury sites can cause decreased insulin and increased cortisol release, is associated
cytotoxicity to vital organs with elevated urinary nitrogen excretion from the normal 7 to 10
o Ischemia-reperfusion injury potentiates this response g per day up to 30 g or more per day.54
byreleasing oxygen metabolites and lysosomal enz.
Although proteolysis during starvation occurs mainly within
PLEASE READ “SURVIVING SEPSIS CAMPAIGN 2017” skeletal muscles, protein degradation in solid organs also occurs.

SURGICAL METABOLISM METABOLISM OF PROLONGED STARVATION
- The initial hours after surgical or traumatic injury are - Proteolysis is reduced to 20g/d and urinary nitrogen
metabolically associated with a reduced total body energy excretion stabilizes to 2-5g/d
expenditure and urinary nitrogen wasting - Organs (myocardium, brain, renal cortex, sk.m) adapt to
- On adequate resuscitation and stabilization of the injured ketone bodies in 2-24 days
patient, a reprioritization of substrate use ensues to preserve - Kidneys utilize glutamine and glutamate in gluconeogenesis
vital organ function and to support repair of injured tissue - Adipose stores provide up to 40% calories (approx 160 g FFA
- This phase of recovery also is characterized by functions that and glycerol)
participate in the restoration of homeostasis, such as - Stimulated by reduced insulin and increased glucagon and
augmented metabolic rates and oxygen consumption, catecholamines
- enzymatic preference for readily oxidizable substrates such
as glucose, and stimulation of the immune system In prolonged starvation, systemic proteolysis is reduced to
approximately 20 g/d and urinary nitrogen excretion stabilizes at
METABOLISM DURING FASTING 2 to 5 g/d.
- Comparable to changes seen in acute injury
- Requires 22-25 (40) kcal/kg/day of carbs, protein, fat This reduction in proteolysis reflects the adaptation by vital
- Normal adult body contains 300-400g carbs (glycogen) – 75- organs (e.g., myocardium, brain, renal cortex, and skeletal
100g hepatic, 200-250g muscle muscle) to using ketone bodies as their principal fuel source

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 METABOLISM FOLLOWING INJURY Surgical Nutrition
- Magnitude of expenditure is proportional to the severity of - Support the requirements for protein synthesis
injury - Nonprotein calorie : nitrogen ratio = 150:1
- Changes in - A lower rate of 80-100:1 may be beneficial in some critically
o Lipid Absorption ill or hypermetabolic patients
o Lipid Oxidation
o Carbohydrate metabolism Basal Energy Expenditure (BEE):
- men = 66.47 + 13.75(W) + 5(H) – 6.76(A) kcal/d
Injuries or infections induce unique neuroendocrine and - women = 655.1 + 9.56(W) + 1.85(H) – 4.68 (A) kcal/d
immunologic responses that differentiate injury metabolism from W= wt in kg,
that of unstressed fasting (Fig. 2-21). H= Ht in cm,
A= age in years
The magnitude of metabolic expenditure appears to be directly
proportional to the severity of insult, with thermal injuries and
severe infections having the highest energy demands

LIPID ABSORPTION
- Oxidation of 1g fat = 9 kcal energy
- Dietary lipids require pancreatic lipase and phospholipase to
hydrolyze TG into FFA and monoglycerides within the
duodenum
- After gut absorption, enterocytes resynthesize TG from
monoglycerides + fatty acyl-CoA
- Long chain TG (>12 carbons) enter the circulation as
chylomicrons. Shorter FA chains directly enter portal
circulation and are transported via albumin
- Under stress, hepatocytes utilize FFA as fuel ENTERAL FEEDING
- Systemically TG and chylomicrons are used from hydrolysis - Less expensive and risks than parenteral
with lipoprotein lipase (suppressed by trauma and sepsis) - Reduced intestinal atrophy
- 44% reduction in infections over parenteral in the critically ill
CARBOHYDRATE METABOLISM - Healthy patients without malnutrition undergoing
- Carbohydrates + pancreatic intestinal enzymes yield dimeric uncomplicated surgery can tolerate 10 d of maintenance IV
units (sucrase, lactase, maltase) fluids only before significant protein catabolism begins
- Intestinal brush border disaccharidases break them into
simple hexose units which are transported into the intestinal Initiation of Enteral Feeding
mucosa - Immediately after adequate fluid resuscitation (UOP)
- Glucose and galactose are absorbed via a sodium dependent - Not absolute prerequisites: presence of bowel sounds,
active transport pump passage of flatus or stool
- Fructose absorption via facilitated diffusion - Gastric residuals of >200ml in 4-6 hrs or abdominal distention
- 1g carbohydrate = 4 kcal energy requires cessation/lowering the rate
- IV/parenteral nutrition 3.4 kcal/g dextrose
- In surgical patients dextrose administration is to minimize Enteral Formulas
muscle wasting - Low-residue isotonic
o caloric density 1.0kcal/ml, 1500-1800 ml/day
PROTEIN AND AMINO ACID METABOLISM o Provide carbs, protein, lytes, water, fat, water sol
- Average adult protein intake 80-120 g/day vitamins, calorie:Nitrogen of 150:1.
o every 6 g protein yields 1 g nitrogen o No fiber bulk = minimum residue
o 1g protein = 4 kcal energy o Standard for stable patients with an intact GI tract
- Following injury, glucocorticoids increase urinary nitrogen - Isotonic with fiber
excretion (>30g/d), peak at 7d, persist 3-7 wks o Soluble and insoluble fiber (soy)
o Delay GI transit time and reduce diarrhea
ADDITIONAL NOTES FROM PPT o Not contraindicated in the critically ill
SURGICAL NUTRITION - Immune-Enhancing
Nutrition in the Surgical Patient o Glutamine, argenine, omega-3 FA, nucleotides, beta-
- Nutritional assessment to determine the severity of carotene.
deficiencies/excess o Benefits not consistent in trials
- Wt loss, chronic illnesses, dietary habits, quality/quantity of o Expensive
food, social habits, meds - Calorie-Dense
- Physical exam – loss of muscle/adipose tissue, organ o 1.5-2 kcal/ml, higher osmolality (ok for intragastric
dysfunction feeding)
- Biochemical – Cr excretion, albumin, prealbumin, total o for fluid restriction/inability to tolerate larger volumes
lymphocyte count, transferrin

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 - High-Protein o Contraindication: distal obstruction, severe intestinal
o Isotonic and nonisotonic available wall edema, radiation enteritis, inflammatory bowel
o calorie:Nitrogen ratio of 80-120:1 disease, ascites, severe immunodeficiency, bowel
- Elemental ischemia
o Contain predigested nutrients, small peptides o Adverse effects: abdominal/bowel distention, cramps,
o Limited complex carbs and fat (long/med chains) pneumotosis intestinalis, small bowel necrosis
o Easily absorbed, but limited long term use
o High osmolality = slow infusion or diluted
o Expensive
- Renal-Failure
o Lower fluid volume, K, phos, and Mg
o Essential aa, high calorie : nitrogen ratio, no vitamins
- Pulmonary-Failure
o Fat content is increased to 50% of total calories
o Reduces CO2 production and ventilation burden
- Hepatic-Failure
o 50% of aa are branched chains (Leu, Ile, Val)
o Potentially reverses encephalopathy
o Controversial, no clear benefits in trials

ENTERAL ACCESS
- Nasogastric Tube - requires intact mental status and
laryngeal reflexes to reduce aspiration
o Difficult to place, requires radiographic confirmation
o If required >30 d, convert to PEG
o Problems: clogging, kinking, inadvertent removal PARENTERAL NUTRITION
- Continuous infusion of hyperosmolar carbs, proteins, fats
and other nutrients through a catheter into the SVC
- Optimal > 100-150 kcal/g nitrogens
- Higher rates of infection compared to enteral
- Studies with parenteral nutrition and complete bowel rest
results in increased stress hormone and inflammatory
responses

Rationale
- Seriously ill patients with malnutrition, sepsis or
surgery/trauma when use of the GI tract for feeding is not
possible
- Percutaneous Endoscopic Gastrostomy – - Short bowel syndrome after massive resection
o Impaired swallowing, bstruction, facial trauma - Prolonged paralytic ileus (>7 days)
o Contra: ascites, coag, gastric varices, gastric neoplasm, - Severe intestinal malabsorption
lack of suitable location - Functional GI disorders – esophageal dyskinesia Etc.
o Tubes can be use for 12-24 mos
o Requires endoscopic transillumination of abdominal wall Total Parenteral Nutrition
and passage of catheter into an insufflated stomach - Central parenteral
o Complications in 3% of cases: infection, peritonitis, nutrition, aka TPN
aspiration/pneumonia, leaks, dislodgement, bowel - Requires access to a large
perforation, enteric fistulas, bleeding diameter vein
- Dextrose content is high
(15-25%)



Peripheral Parenteral Nutrition
- Lower osmolality
- Reduced dextrose (5-10%)
- Protein (3%)
- Not appropriate for severe
malnutrition due to need for
larger volumes of some
- Surgical Gastrostomy Tube nutrients
o With complex abdominal trauma/laparatomy there may - Shorter periods, < 2 wks
be an opportunity for placement

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 Parenteral Nutrition
- Dextrose 15-25%
- Amino acids 3-5%
- Vitamins (Vit K is not included)
- Lipid emulsions to prevent essential FA deficiency (10-15% of
calories)
- Prepared by the pharmacy from commercially available kits
- If prolonged – supplement trace minerals
o Zinc (eczematous rash), copper (microcytic anemia),
chromium (glucose intolerance)
- Insulin supplement to insure glucose tolerance
- IV fluids/electrolytes if high fluid losses
- Freq. monitor fluid status, vital signs, UOP, electrolytes, BUN,
and LFTs. Glucose q6h

Complications
- Hyperglycemia – pt with impaired glc tolerance or high
infusion rate
o Tx- volume replacement, correct electrolytes, insulin
o Avoid by monitoring daily fluid balance, glc, & lytes
- Overfeeding – results in CO2 retention and respiratory
insufficiency
- Hepatic steatosis
- Cholestasis and gallstones
- Hepatic abnormalities – serum transaminase, alk phos and
bilirubin
- Intestinal - atrophy from disuse, bacterial overgrowth,
reduced lymphoid tissue and IgA production, impaired gut
immunity

Special Formulations
- Glutamine and Arginine
o Glutamine – nonessential aa, comprises 66% of free
amino acids
o During stress glu is depleted and shunted as a fuel
source to visceral organs and tumors
o Inconclusive data for benefits of increased
supplementation
o Arginine – nonessential aa, promotes net nitrogen
retention and protein synthesis in the critically
ill/injured. Benefits still under investigation.
- Omega-3 Fatty Acids
o Canola or fish oil. Displaces omega-6 FAs, theoretically
reducing pro-inflammatory responses
- Nucleotides
o Increase cell proliferation, DNA synthesis, T Helper cell
function














Notes from Lecture PPT, Winter_MD Trans

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