SYSTEMIC RESPONSE

TO INJURY
James Taclin C. Banez, MD, FPSGS, FPCS

Injury (surgery, traumatic & infections):

Alteration of neuro-endocrine
system, metabolic and immunology
----> causes disequilibrium of internal
environment & tries to return to
homeostasis.

 Minor Injuries: is usually followed by

functional restoration w/ minimal

intervention.
Major injuries: associated with

overwhelming inflammatory response ---->

failure to give appropriate intervention
----> multiple organ failure -----> DEATH

Systemic Inflammatory
Response Syndrome (SIRS)

2 Phases:
1. Pro-inflammatory
phase:

2.

Char. By activation of
cellular processes
designed to restore tissue
function & eradicate
invading micro-organism.

Counter-regulatory or
anti-inflammatory
phase:

To prevent excessive proinflammatory activities

and to restore
homeostasis

Terminologies
Term

Definition

Infection Identifiable source of microbial insult

SIRS

Two or more following criteria:

- Temp >/= 38C or </= 36C
- Heart rate >/= 90 beats/min
- Respiratory rate >/= 20 breaths/min or PaCO2 </= 32mmHg
or mechanical ventilation
- WBC >/= 12,000/ul or </= 4000/ul or >/= 10% band forms

Sepsis

Identifiable source of infection + SIRS

Severe
sepsis

Sepsis + organ dysfunction

Septic
shock

Sepsis + cardiovascular collapse (requiring vasopressor

support)

Central Nervous System

Regulation of Inflammation
Afferent Signals:
1. Circulatory:

2.

Areas of CNS devoid of

bld-brain barrier admit
passage of inflammatory
mediators (TNF)
Causing fever, anorexia &
depression

Neural pathways:

1.
2.
3.
4.

Afferent stimuli to the

vagus nerve:
cytokines TNF, IL-1
Baroreceptors
Chemoreceptors
Thermoreceptors
From the site of injuries

Central Nervous System

Regulation
of
Inflammation
Cholinergic Anti

Inflammatory
Pathways:
Acetycholine of
parasympathetic:

1.

2.

reduces tissue macrophage

activation
Reduces tissue macrophage
release of inflammatory
mediators (TNF alpha, IL1,
IL18 & high mobility grp
protein (HMG-1), but not the
anti-inflammatory cytokine
IL10

Vagal stimulation
reduces HR, increases
gut motility, dilates
arterioles, causes pupil
constriction & regulates
inflammation

Systemic Neuro-Endocrine Reflexes

Stimuli:
1.

Effective Circulatory Volume (ECV):

Sensed by:
a)
b)

high pressure baroreceptor (aorta, carotid & renal artery)

low pressure stretch receptors (atrial volume)

Decreased ECV ---> release of tonic inhibition ---> (+)

receptors ----> (+) ACTH, vasopressin , betaendorphin, E & NE, renin.

If decrease ECV is < 30% of TBV the neuroendocrine

& cardiovascular response can compensate; > 30%
----> DECOMPENSATE (hypotension)

Systemic Neuro-Endocrine
Reflexes

Stimuli:
2.

Chemoreceptor Relexes:

sensed by:
a. carotid bodies (inactive)
b. aortic bodies (inactive)

stimulation of chemoreceptors:
1.
2.

decrease oxygen
increase CO2 and H

Results to:
1.

2.

Decrease sympathetic activity (cardiac) & increase in

parasympathetic activity.
Increase respiratory rate & decrease cardiac rate and
contractility.

Systemic Neuro-Endocrine
Reflexes
Stimuli:
3.

Pain & Emotion:

4.

Pain ---> (+) thalamus & hypothalamus

Emotion ---> (+) limbic ----> (+) hypothalamus

Substrate alteration:

Alteration plasma glucose concentration activates

neuroendocrine reflexes thru its receptors:
a)
b)

5.

Hypothalamus -----> pituitary

Pancreas

Temperature:

Changes in core temperature, sensed by the pre-optic area

of the hypothalamus ---> alters secretion of several
hormones

Systemic Neuro-Endocrine
Reflexes
CNS Centers: (hypothalamus)
Posterior Hypothalamus:

1.

ACTH, sympathetic activity

Paraventricular Nucleus:

2.

vasopressin, oxytocin & ACTH

Ventromedial Nucleus:

3.

GH, ACTH

Supraoptic Nucleus

4.

vasopressin & oxytocin

Suprachiasmatic Nucleus:

5.

ACTH & gonadotrophin

Systemic Neuro-Endocrine
Reflexes
Efferent Output:
1.

Autonomic response:

1.

Hormonal response:

2.

Hypothalamic anterior pituitary control

Posterior pituitary control
Autonomic control

Local tissue response:

Hormone Response to Injury

Hypothalamic regulation
1.
2.
3.
4.

CRH
TRH
GHRH
LHRH

Anterior Pituitary regulation

1.
2.
3.
4.
5.
6.
7.
8.
9.

ACTH cortisol
TSH T3/T4
GH
Gonadotrophins
Sex hormones
Insulin-like growth factor
Somatostatin
Prolactin
Endorphins

Posterior Pituitary
regulation
1.
2.

Vasopressin
Oxytocin

Autonomic System
1.
2.
3.
4.
5.
6.

NE / E
Aldosterone
Renin-angiotensin system
Insulin
Glucagon
Enkephalins

HORMONES UNDER ANTERIOR PITUITARY

REGULATION
1. CRF ACTH Cortisol:
a.

(+) CRF

a.

ACTH

b.

Cortisol -

pain, fear, anxiety, angiotensin II, serotonin,

acetylcholine & interleukin 1/6

circardian signals is lost in injury due to pain,

anxiety, vasopressin, angiotensin II, E,
NE, oxytocins & proinflammatory cytokines
elevated in any types of injury, longest in burn
pts. (4wks). Actions in injury:

b.
c.

d.

e.

potentiates the action of glucagon & E causing hyperglycemia.

favors gluconeogenesis; insulin resistance in muscles & adipose
tissue.
induces protein degradation in the skeletal muscle & releases
lactate for hepatic gluconeogenesis
potentiates release of FA, triglycerides & glycerol from adipose
tissue for energy source

CRF ACTH Cortisol:

1.

Acute adrenal Insufficiency (AAI):

Life threatening complication

Commonly due to adrenal suppression from exogenous
administration of glucocorticoid
Manifestation:
1.
weakness, n / v, fever & hypotension
2.
Hypoglycemia (due to low gluconeogenesis)
3.
Hyponatremia & Hyperkalemia (impaired renal tubular
reabsorption due to insufficient aldosterone)

Cortisol is an effective immuno-suppressive agents:

1.
2.
3.

4.

Caused thymic involution

Depressed cell mediated immune response
Cause monocyte & neutrophil lose of intracellular bacterial
killing
It downregulates proinflammatory cytokines production (TNF
alpha, IL-1, IL-6); and increases the production of antiinflammatory mediator IL-10.

Growth Hormone:

2.

(+) GH is GHRF
(-) GH is somatostatin
Anabolic for CHON; catabolic for CHO & lipids
Stimulatory:

Hypoglycemia, decrease ECV, decrease plasma FA & a.a.,

exercise, STRESS and sleep.

Thyroxine, vasopressin, MSH, testosterone, estrogen and

alpha adrenergic stimulation.

INSULIN like GROWTH FACTOR-1

(Somatomedin C; IGF-1)
1.

2.
3.

4.

Partially mediates CHON synthesis properties of GH after

injury
The liver is the predominant source of IGF-1.
Promotes a.a. incorporation & cellular proliferation and
attenuates proteolysis in skeletal muscle & liver.
In injury: the effects of IGF-1 is inhibited by
proinflammatory cytokines (TNF, IL-1 and IL-6).
Resulting to (-) nitrogen balance.

Macrophage Inhibitory Factor:

3.

Produced by:
a.
Anterior pituitary gland
b.
T lymphocytes at the site of inflammation.
Actions:
a.
A glucocorticoid antagonist (suppresses the immunosuppresive
effects of cortisol).
b.
It is a proinflammatory mediator that potentiates gm (-) & (+)
septic shock.

Endogenous Opiods:

4.

Endorphins, enkephalins
Elevated after injury & surgery
Endorphins ----> attenuate pain perceptions / hypotension
Enkephalins ----> HPN, decrease peristalsis and secretion of GIT

Thyroid Hormone (T4 / T3):

5.

In injury:
a.
Low T3
b.
(-) TSH release
c.
Conversion of T4 T3 in the target organs are impaired
due to cortisol. T4 is converted to an inactive T3 called rT3

Gonadotrophins (LHRH/GnRH) & (FSH/LH):

6.

Injury, stress or severe illness ----> (-) GRH ----> (-) LH and
(-) FSH ---> decrease estrogen and androgen secretions.
Causes menstrual irregularities and decrease libido.

Prolactin:

7.

Produced by anterior pituitary gld and T lymphocytes

Elevated level after injury in adults not seen in children
Causes amenorrhea

HORMONES OF AUTONOMIC SYSTEM:

Catecholamines (E / NE):

1.

Causes hypermetabolic state following severe injury

3 4fold increase of E & NE in the plasma for 24 48
hrs.
Causes:
a. Promotes glycogenolysis, gluconeogenesis,
lipolysis and ketogenesis.
b. Decreased insulin release & increase glucagon
secretion.
c.
Peripherally, it increases lipolysis in adipose tissue
and induces insulin resistance in skeletal muscle
d. It inhibit the release of aldosterone.
e. Immune function: -- enhances neutrophilia and
lymphocytosis

Aldosterone (Mineralocorticoid):

2.

Released by adrenal zona glomerulosa

Release is caused by:
1. Angiotensin II
2. Hyperkalemia
3. Aldosterone stimulating factor (ASF) in pituitary
4. ACTH (is the most potent stimulant).
Major function is to maintain intravascular volume
by conserving Na & eliminating potassium and H+ in
the early distal convoluted tubules of nephron

Renin Angiotensin:

3.

Renin in Juxtaglomerular apparatus is released by:

a. ACTH, Glucagon, porstagladin, K+, Mg+, and Ca+
b. Baroreceptor respond to decrease blood pressure
c.
Macula densa detects changes in chloride
concentration.

Action of angiotensin II:

a. Vasoconstrictor
b. (+) aldosterone
c.
(+) ADH
d. (+) E
e. Increase heart rate and contractility

4.

Glucagon:

5.

alpha islet cell

catabolic role
elevated release after injury

Insulin:

Inhibit its release in injury:

a.
b.
c.
d.
e.

Catecholamine
Glucagon
Somatostatin
Beta endorphins
IL-1

Hormones Under Posterior Pituitary

Regulation:
1. Vasopressin / ADH / Arginine
Vasopressin (AVP):
Causes
a.
b.
c.

readsorption of H2O in DCT

Vasoconstriction peripherally
Stimulates hepatic glycogenolysis &
gluconeogenesis

Elevated plasma osmolality is its major

stimulus:
Location of osmoreceptors: hypothalamus,
portal circulation

Hormones Under Posterior Pituitary

Regulation:
1. Vasopressin / ADH / Arginine
Vasopressin (AVP):

Its release also happens in 10% loss of ECV

stimulating the baroreceptor in the left atrium
Other stimulus:
1.
2.
3.
4.
5.

PAIN
Beta adrenergic
Angiotensin II
Opiods
Elevated glucose

Oxytocin:

2.

Its release caused by SUCKING the nipple

Stimulates contraction of mammary gland
and uterus during parturition
No known function in males
Role in injury is unknown

Mediators of Inflammation
Cytokines:

1.

Most potent mediator of the inflammatory response

Eradicates invading microorganism and promotes
wound healing
Overwhelming productions of proinflammatory
cytokines can cause:
a.
b.

Hemodynamic instability (septic shock)

Metabolic derangement (muscle wasting)

Can exaggerate to multiple organ failure and death.

Inappropriate anti-inflammatory mediator release
can lead to immunocompromised and susceptible to
overwhelming infection.

Mediators of Inflammation
Heat Shock
Proteins:

2.

Intracellular protein
modifiers and
transporters that
protect cells from the
deleterious effects of
traumatic stress.
The following induced
its production:
a.
b.
c.
d.
e.

Hypoxia
Trauma
Heavy metals
Local trauma
Hemorrhage

Mediators of Inflammation
Reactive Oxygen Metabolites:

3.

Oxygen radicals are produced by reduction of

oxygen to superoxide anion, and further
metabolized to form H2O2 & hydroxyl radicals
Causes injury by oxidation of unsaturated fatty
acids w/in cell membranes.
Activated leukocytes are potent generators for
reactive oxygen metabolites.
Cells are protected from this metabolite by
oxygen scavengers: GLUTATHIONE &
CATALASES.

Mediators of Inflammation
4.

Eicosanoids:

Are oxidation derivatives of

membrane phospholipid
arachidonic acids
Secreted by nucleated cells,
except lymphocytes
Not stored w/in cells but are
synthesized rapidly upon
stimulation by hypoxic
injury, tissue injury,
endotoxin, NE, vasopressin
angiotensin II, bradykinin,
serotonin, acetylcholine,
cytokines and histamine

Mediators of Inflammation
4.

Eicosanoids:
Actions:
a.
PGE2 increases fluid leakage
from bld vessels, inhibit
gluconeogenesis and
hormone stimulated lipolysis.
b.

Leukotrienes are 1000x

more potent than histamine
promoting capillary leakage,
vasoconstriction,
bronchoconstriction,
neutrophil activation.

c.

Products of
cyclooxygenase inhibit
pancreatic beta cell release
of insulin.

Mediators of Inflammation
5.

Kallikrein-Kinin System:
Bradykinin:

a.

potent vasodilators
Release is caused by hypoxic and ischemic
injury

Kinins:

b.

increase capillary permeability and tissue edema,

evoke pain,
Inhibit gluconeogenesis
increase bronchoconstriction.
increase renal vasodilation and reduces renal
perfusion pressure ----> (+) renin-angiotensin
system.

Mediators of Inflammation
Serotonin:

6.

neurotransmitter (5hydrohytryptamine)
tryptophan derivative found in chromaffin
cells of the intestine (carcinoid tumors).
Vasoconstrictions, bronchoconstriction &
platelet aggregations
myocardial chronotrope and inotrope

Mediators of Inflammation
7.

Histamine:

Derived from histidine

Stored in neurons, skin, gastric mucosa,
mast cells basophils and platelets
Released is activated by increased
calcium levels.

2 receptors:
a. H1 stimulates bronchoconstriction,
intestinal motility, and myocardial
contractility
b. H2 inhibits histamine release

Mediators of Inflammation
7.

Histamine:
Both H1 & H2 receptor activation causes:
a.
b.
c.
d.
e.

Hypotension
Peripheral pooling of blood
Increase capillary permeability
Decrease venous return
Myocardial failure

Elevated in cases of hemorrhagic shock,

trauma, thermal injury, endotoxemia and
sepsis.

Cytokines

Usually secreted by immunocytes & other cells

Indespensible to tissue healing and immune response

generated against microbial invasion

Are not stored as preformed molecules and its activity is

primarily exerted locally w/ cell to cell interaction

Their rapid appearance after injury is due to active

transcription and translation by the injured or stimulated
cells.

Direct the inflammatory response to infection, injury and

actively promote wound healing

CYTOKINES
TNF (Tumor Necrosis Factor):

1.

Earliest & most potent mediators

Monocytes/macrophage and Tcells
Actions:
1.

2.
3.

4.

Major inducer muscle catabolism & cachexia

during stress
Coagulation activation
Releases prostaglandin E2, platelet activating
factor (PAF), glucocorticoid and eicosanoids
Initiates of hemodynamic decompensation.

CYTOKINES
2.

Interleukin-1 (IL-1):
Causes:
a.

b.

Induces febrile response to injury by stimulating

prostaglandin to anterior hypothalamus.
Attenuated pain perception by promoting
release of beta-endorphins from the pituitary gld.

Endogenous IL-1 receptor antagonist (IL-1ra) are

also released during injury to auto-regulate IL-1.

CYTOKINES
3.

Interleukin-2:

Promoter of T-lymphocyte proliferation,

immunoglobulin production & gut
barrier integrity.

CYTOKINES
Interleukin-4 (IL-4):

4.

Produced by activate T-helper lymphocyte.

Induces B lymphocyte to produce IgG & IgE
impt. for allergy and anthelmintic responses.
Potent anti-inflammatory properties, it
downgrades the effects of:
a. IL-1
b. TNF-alpha
c. IL-6
d. IL-8
e. Increases macrophage susceptibility to
the anti-inflammatory effects of
glucocorticoid

CYTOKINES
Interleukin-6 (IL-6):

5.

Produced by all cells & tissues

Fnx:
a. It induces neutrophil activation and
delay its disposal leading to the cells
prolonged injurious effect
b. It can also attenuate TNF & IL-1 by
promoting the release of soluble tumor
necrosis factor receptors and IL-1
receptor antagonists.

CYTOKINES
Interleukin-8 (IL-8):

6.

Activity is similar to IL-6

Biomarker for the risk of multiple organ
failure
Does not produced hemodynamic instability
but is a chemoattractant and activator of
neutrophil

CYTOKINES
Interleukin-10 (IL-10):

6.

It reduces TNF-alpha
Attenuate systemic inflammatory
response and reduces mortality during
septic peritonitis
Associated w/ increased bacterial load &
mortality

CYTOKINES
10.

Interleukin-12 (IL-12):
Primary role in cell-mediated immunity &
promotes differentiation of TH1 cells.
Inducing an inflammatory response for
48hrs, independently from TNF & IL-1.
Promotes neutrophil & coagulation activation
Toxicity is synergistic w/ IL-2.

CYTOKINES
Interleukin-13 (IL-13):

11.

Structural & functional similarities w/ IL-4

Modulate macrophage function
Inhibit nitric oxide production & the
expression of proinflammatory cytokines
and enhance production of IL-1ra
It attenuates leukocyte interaction w/
activated endothelial surfaces

CYTOKINES
12.

Interleukin-15 (IL-15):
Potent autocrine regulatory properties.
Possess similar bioactivity in promoting
lymphocyte activation & proliferation
Induces IL-8 production.

13.

Interleukin-18 (IL-18):

Formerly interferon (IFN)-y-inducing factor

Proinflammatory cytokine
Structurally similar to IL-1beta & functionally
similar to IL-12.

CYTOKINES
14.

Interferon-y:

Produced by Helper T lymphocytes when

activated by bacterial antigens, IL-2, IL-12,
IL-18
Can also induce production of IL-2, IL-12,
IL-18
Elevated for as long as 8 days.
Can activate circulating and tissue
macrophage
Alveolar macrophage activation may induce
acute lung inflammation after major surgery
or trauma.

CYTOKINES
15.

Granuloctye-Macrophage ColonyStimulating Factor (GMC-SF):

Delays apoptosis of macrophages and
neutrophils; contribute to organ injury
(ARDS)
Promote maturation and recruitment of
functional leukocytes needed for normal
inflammatory cytokine response & potentially
in wound healing.

Cell-Mediated Inflammatory
Response
Platelets:

1.

Clot formed at the site of injury releases

inflammatory mediators w/c serves as the
principal chemo-attractant for neutrophils
and monocytes.
Migration of platelets & neutrophils through
the vascular endothelium occurs w/in 3 hrs
of injury and mediated by:
a. Serotonin
b. Platelet-activating factor
c. Prostaglandin E2

Cell-Mediated Inflammatory
Response
Lymphocytes & Tcell Immunity:

2.

Injury associated w/
Acute impairment of
cell-mediated
immunity and
macrophage function
2 subgroups of Thelper lymphocytes:
a.
b.

TH 1
TH 2

Cell-Mediated Inflammatory
Response
Eosinophils:

3.

Migrate to inflammed endothelium and release

cytoplasmic granules that are cytotoxic
It preferentially migrate to sites of parasitic infection
and allergy
Resides in GIT, lung and genitourinary tissues
Major activators:
a.
b.
c.
d.

IL-3
IL-5
Platelet-activating factor
Complement anaphylatoxins C3a and C5a

Cell-Mediated Inflammatory
Response
Mast Cells:

4.

When activated it produce:

a.
b.

c.
d.
e.

Histamine
Cytokines (IL-3, IL4, IL-5, IL-6, IL-10, IL-13, IL-14
& migration-inhibitory factor (MIF).
Eicosanoids
Proteases
Chemokines

Cell-Mediated Inflammatory
Response
4.

Mast Cells:

Immediate results:
a.
b.
c.

Vasodilation
Recruitment of other immunocytes
Capillary leakage

TNF-alpha secreted rapidly by this cell

bec. of its abundant source

Cell-Mediated Inflammatory
Response
Monocytes:

5.

There is down regulation in monocyte and

neutrophil TNFR expression
In none surviving pts w/ severe sepsis and failed to
recover, an immediate reduction in monocyte
surface TNFR expression was observed, while
surviving pts have normal or near normal receptor
levels

Neutrophils:

6.

Inflammatory mediators from site of injury induces

neutrophil adherence to the injured tissue.
Its function is mediated by vast array of intracellular
granules that are chemotactic or cytotoxic to local
tissue & invading microorganisms.

Endothelium-Mediated Injury
Neutrophil-Endothelium Interaction:

1.

Inc. vascular permeability during inflammation is

intended to facilitate O2 delivery and immunocyte
migration to the site of injury.
However accumulation & infiltration of leukocytes
(neutrophil) contribute to the cytotoxicity of vital
tissue ---> MOF.
Ischemia/reperfusion injury potentiates this
response by:
a.
b.
c.
d.

unleashing oxygen metabolites

Lysosomal enzymes that degrade tissue basal membranes
Cause microvascular thrombosis
Activate myeloperoxidases.

Endothelium-Mediated Injury

Recruitment of
circulating neutrophils
to endothelial
surfaces is mediated
by actions of
adhesive molecules
called SELECTINS
(L,P,E)

Endothelium-Mediated Injury
Nitric Oxide:

2.

Formed from oxidation of L-arginine

Derived from endothelial surfaces
Cells that produces this subs:
a.
b.
c.
d.
e.

Neutrophil
monocytes
Renal cells
Kupffer cells
Cerebellar neurons

Action:
a.
b.

c.

Maintain normal smooth muscle relaxation

Reduce thrombosis by reducing platelet
adhesions and aggregation
Mediates protein synthesis in hepatocyte

Endothelium-Mediated Injury
Prostacyclin:

3.

3.

Induces vaso-relaxation and platelet deactivation by increasing

cAMP

Endothelins:
Formed by vascular endothelial cells in response to:
a.
b.
c.
d.
e.
f.
g.
h.

Injury
Thrombin
Transforming growth factor-B (TGF-B)
IL-1
Angiotensin II
Vasopressin
Catecholamine
Anoxia

Action:
The MOST POTENT vasoconstriction (10 x more angiotensin II)
Vasoconstriction is reversed by acetylcholine

Endothelium-Mediated Injury
Platelet-Activating Factor:

5.

Released by neutrophils, platelets, mast cells and

monocytes
It activate neutrophils and platelets and increase
vascular permeability.

Atrial Natriuretic Peptides:

6.

Released by atrial tissue, gut, kidney, brain, adrenal

glds and endothelium
Actions:
a.
b.
c.

Vasodilator and induce fluid and electrolyte excretion

Inhibits aldosterone secretion
Prevent reabsorption of sodium

END OF
FIRST PART

Metabolic Changes and

Nutritional Management
of Surgical Patients
James Taclin C. Banez, MD, FPSGS,
FPCS

Majority of surgical patients:

well nourished / healthy
uncomplicated major surgical procedure
has sufficient fuel reserve
can withstand brief period of catabolic insult

and starvation of 7 days

Postoperatively:
can resume normal oral intake
supplemental diet is not needed

Surgical Patients that Needs

Nutritional Support

To shorten the postoperative recovery

phase and minimize the number of
complications:
1.

2.

Chronically debilitated from their diseases or

malnutrition.
Suffered severe trauma, sepsis or surgical
complications

Metabolic Changes in Surgical Patients

Metabolic events brought about by

STIMULI:
1.
2.

Injury
Starvation

Metabolic response is directed to restore:

1. Homeostasis
2. Repair

Metabolic Response to

Starvation
HYPOGLYCEMIA is primary stimulus
Hormonal Changes: increase cortisol, catecholamines,
glucagon, growth hormones
Primary gluconeogenic precursors by the liver & kidney:
a. lactate b. glycerol c. amino acid (alanine & glutamine)

Proteolysis increase due to increase CORTISOL

------> inc. urinary nitrogen first 4 days of starvation
(8-12g/day = 6.25g of muscle/g of nitrogen).

Protein catabolism for gluconeogenesis primarily comes

from SKELETAL muscle, but in pure starvation other
organs are involved

In liver. CHON loss is selective; spare enzymes for

gluconeogenesis and lipolysis.
In pancreas and GIT, enzymes for digestion and protein for
regeneration of epithelium is involved -> PARADOXICAL
FOOD INTOLERANCE

Rapid proteolysis of body CHON cannot proceed at 75

g/day for long, or else patient will die immediately
RANDLE EFFECT.
decrease urinary excretion of nitrogen 2 4 gm/day due
to keto-adaptation of the brain
decrease protein degeneration and major source of
energy is FAT (90%)

Metabolism of Injured Patient

PHASES:
1. Catabolic phase (Ebb, AdrenergicCorticoid):

immediately following surgery or trauma

characterized w/ hyperglycemia, increase
secretion of urinary nitrogen beyond the level
of starvation
caused by increase glucagon,
glucocorticoid, catecholamines and
decrease insulin
tries to restore circulatory volume and tissue
perfusion

Metabolism of Injured Patient

PHASES:
2. Early anabolic phase (flow, corticoidwithdrawal):

tissue perfusion has been restored, may last for days

to months depending on:
a. severity of injury
b. previous health
c. medical intervention
sharp decline in nitrogen excretion
nitrogen balance is positive (4g/day) indicating
synthesis of CHON and there is a rapid and
progressive gain in weight and muscular strength

Metabolism of Injured Patient

PHASES:
3. Late anabolic phase:

several months after injury

occurs once volume deficit have been
restored
slower re-accumulation of CHON
re-accumulation of body fat

Metabolism of Injured Patient

Carbohydrate Metabolism in Injured
Patient:
Hyperglycemia = proportional to the severity of
injury

Importance:
1. Homeostatic significance
2. Ready source of energy to the brain
3. Adequate delivery
Caused by:

Increased catecholamine (primarily), cortisol, glucagon,

GH, vasopressin, angiotensin II, somatostatin and
decrease insulin.

Metabolism of Injured Patient

Carbohydrate Metabolism:
Hyperglycemia:

Caused by:
Increased catecholamine (primarily), cortisol,
glucagon, GH, vasopressin, angiotensin II,
somatostatin and decrease insulin.
Gluconeogenesis in liver and kidney and
impaired peripheral uptake of glucose

Metabolism of Injured Patient

Carbohydrate Metabolism:
Hyperglycemia:

Insulin resistance:
During the Ebb phase there is reduction in beta cell
sensitivity to glucose due to Catecholamine,
somatostatin and reduced pancreatic blood flow
Resistance to exogenous administration on
insulin in both EBB and early FLOW phases
In middle and late Flow phase, beta cell sensitivity
return to normal and its level is higher, but
hyperglycemia persist because of continuous
gluconeogenesis

Metabolism of Injured Patient

Carbohydrate Metabolism:
Glucose metabolism in wounded tissue :

Increase glucose uptake and lactate production

because of anaerobic glycolysis due to local
tissue hypoxia
(+) insulin insensitivity

Metabolism of Injured Patient

Lipid metabolism:

primary source of energy

Best stimulus for hormone-sensitive lipase is
CATECHOLAMINE
RANDLE EFFECT is not present

Metabolism of Injured Patient

Protein Metabolism:

Nitrogen urine excretion 30-50g/day due to proteolysis;

20% utilized for energy (calories) the rest for
gluconeogenesis by liver and kidney (cortisol,
glucagon, catecholamine).
Primary source of protein is the skeletal muscle and
the visceral organs are spared.
Ketoadaptation is inhibited ----> gluconeogenesis
persist ---> proteolysis persist (INTERLEUKIN I).
The degree and duration (-) nitrogen balance is related
to severity of injury. The net CHON catabolism depends
on the age, sex and physical condition of the patient (>
in young, healthy and male)
(-) nitrogen balance can be reduced by high caloric
nitrogen supplement

Traumatized Man

Injury of any type is associated with:

1. Immobilization
2. Starvation
3. Repair
the first two are associated with reduction in
energy requirement. While the third is
associated w/ increase energy requirement
The amount of energy produced in injured pt.
is not optimum, to supply necessary energy
for the repair due to:
1.
reduced or absent nutritional intake
2.
significant reduction of energy charge and ATP
content during shock, hypoxia, sepsis,
ischemia and wound - anaerobic
metabolism

REE (Resting energy expenditure) by

Harris and Benedict:
(MEN) 66.47 + 13.75 (W) + 5.0 (H) 6.76 (A)
= Kcal/day

(Female) 65.51 + 9.56 (W) + 1.85 (H) 4.68 (A)

= Kcal/day
Fever: increase resting energy expenditure of
approximately 7% for each degree of F of fever.