systemic response to injury

SYSTEMIC RESPONSE SYSTEMIC RESPONSE TO INJURYTO INJURY

James Taclin C. Banez, MD, FPSGS, FPCSJames Taclin C. Banez, MD, FPSGS, FPCS

InjuryInjury (surgery, traumatic & infections):(surgery, traumatic & infections): Alteration of Alteration of neuro-endocrine neuro-endocrine

system, metabolicsystem, metabolic and and immunologyimmunology ----> causes disequilibrium of internal ----> causes disequilibrium of internal environment & tries to return to environment & tries to return to homeostasis.homeostasis.

Minor InjuriesMinor Injuries: is usually followed by : is usually followed by functional restoration w/ minimal functional restoration w/ minimal intervention.intervention.

Major injuriesMajor injuries: associated with : associated with overwhelming inflammatory response ----> overwhelming inflammatory response ----> failure to give appropriate intervention ----> failure to give appropriate intervention ---->

multiple organ failure -----> multiple organ failure -----> DEATHDEATH

Systemic Inflammatory Systemic Inflammatory Response Syndrome (SIRS)Response Syndrome (SIRS)

2 Phases:2 Phases:

1.1. Pro-inflammatory Pro-inflammatory phase:phase:

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

2.2. Counter-regulatory or Counter-regulatory or anti-inflammatory anti-inflammatory phase:phase:

To prevent excessive pro-To prevent excessive pro-inflammatory activities inflammatory activities and to restore and to restore homeostasishomeostasis

TerminologiesTerminologiesTermTerm DefinitionDefinition

InfectionInfection Identifiable source of microbial insultIdentifiable source of microbial insult

SIRSSIRS

Two or more following criteria:Two or more following criteria:

- Temp >/= 38C or </= 36C- Temp >/= 38C or </= 36C

- Heart rate >/= 90 beats/min- Heart rate >/= 90 beats/min

- Respiratory rate >/= 20 breaths/min or PaCO2 </= 32mmHg- Respiratory rate >/= 20 breaths/min or PaCO2 </= 32mmHg

or mechanical ventilationor mechanical ventilation

- WBC >/= 12,000/ul or </= 4000/ul or >/= 10% band forms- WBC >/= 12,000/ul or </= 4000/ul or >/= 10% band forms

SepsisSepsis Identifiable source of infection + SIRSIdentifiable source of infection + SIRS

Severe Severe sepsissepsis

Sepsis + organ dysfunctionSepsis + organ dysfunction

Septic Septic shockshock

Sepsis + cardiovascular collapse (requiring vasopressor Sepsis + cardiovascular collapse (requiring vasopressor support)support)

Central Nervous System Central Nervous System Regulation of InflammationRegulation of Inflammation

Afferent Signals:Afferent Signals:1.1. Circulatory:Circulatory:

Areas of CNS devoid of Areas of CNS devoid of bld-brain barrier admit bld-brain barrier admit passage of inflammatory passage of inflammatory mediators (TNF)mediators (TNF)

Causing fever, anorexia & Causing fever, anorexia & depressiondepression

2.2. Neural pathways:Neural pathways: Afferent stimuli to the Afferent stimuli to the

vagus nervevagus nerve: : 1.1. cytokines – TNF, IL-1cytokines – TNF, IL-12.2. BaroreceptorsBaroreceptors3.3. ChemoreceptorsChemoreceptors4.4. Thermoreceptors Thermoreceptors From the site of injuriesFrom the site of injuries

Central Nervous System Central Nervous System Regulation of InflammationRegulation of Inflammation

Cholinergic Anti-Cholinergic Anti-Inflammatory Inflammatory Pathways:Pathways:

Acetycholine of Acetycholine of parasympathetic:parasympathetic:

1.1. reduces tissue macrophage reduces tissue macrophage activationactivation

2.2. Reduces tissue macrophage Reduces tissue macrophage release of inflammatory release of inflammatory mediators (TNF alpha, IL1, mediators (TNF alpha, IL1, IL18 & high mobility grp IL18 & high mobility grp protein (HMG-1), but not the protein (HMG-1), but not the anti-inflammatory cytokine anti-inflammatory cytokine IL10IL10

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

Systemic Neuro-Endocrine ReflexesSystemic Neuro-Endocrine Reflexes

Stimuli:Stimuli:1.1. Effective Circulatory Volume (ECV):Effective Circulatory Volume (ECV):

Sensed by: Sensed by: a)a) high pressure baroreceptorhigh pressure baroreceptor (aorta, carotid & renal artery) (aorta, carotid & renal artery)b)b) low pressure stretch receptorslow pressure stretch receptors (atrial volume) (atrial volume)

Decreased ECV ---> release of tonic inhibition ---> (+) Decreased ECV ---> release of tonic inhibition ---> (+) receptors ----> (+) ACTH, vasopressin , beta-receptors ----> (+) ACTH, vasopressin , beta-endorphin, E & NE, renin. endorphin, E & NE, renin.

If decrease ECV is < 30% of TBV the neuroendocrine If decrease ECV is < 30% of TBV the neuroendocrine & cardiovascular response can compensate; > 30% & cardiovascular response can compensate; > 30%

----> ----> DECOMPENSATE (hypotension) DECOMPENSATE (hypotension)

Systemic Neuro-Endocrine Systemic Neuro-Endocrine ReflexesReflexes

Stimuli:Stimuli:2.2. Chemoreceptor Relexes:Chemoreceptor Relexes:

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

(inactive)(inactive)

stimulation of chemoreceptors:stimulation of chemoreceptors:1.1. decrease oxygendecrease oxygen2.2. increase CO2 and Hincrease CO2 and H

Results to:Results to:1.1. Decrease sympathetic activity (cardiac) & increase in Decrease sympathetic activity (cardiac) & increase in

parasympathetic activity.parasympathetic activity.2.2. Increase respiratory rate & decrease cardiac rate and Increase respiratory rate & decrease cardiac rate and

contractility.contractility.


Stimuli:Stimuli:3.3. Pain & Emotion:Pain & Emotion:

Pain ---> (+) thalamus & hypothalamusPain ---> (+) thalamus & hypothalamus Emotion ---> (+) limbic ----> (+) hypothalamusEmotion ---> (+) limbic ----> (+) hypothalamus

4.4. Substrate alteration:Substrate alteration: Alteration plasma glucose concentration activates Alteration plasma glucose concentration activates

neuroendocrine reflexes thru it’s receptors:neuroendocrine reflexes thru it’s receptors:a)a) Hypothalamus -----> pituitaryHypothalamus -----> pituitaryb)b) PancreasPancreas

5.5. Temperature:Temperature: Changes in core temperature, sensed by the pre-optic area Changes in core temperature, sensed by the pre-optic area

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


CNS Centers: CNS Centers: (hypothalamus)(hypothalamus)1.1. Posterior Hypothalamus: Posterior Hypothalamus:

• ACTH, sympathetic activityACTH, sympathetic activity

2.2. Paraventricular Nucleus:Paraventricular Nucleus:• vasopressin, oxytocin & ACTHvasopressin, oxytocin & ACTH

3.3. Ventromedial Nucleus:Ventromedial Nucleus:• GH, ACTHGH, ACTH

4.4. Supraoptic NucleusSupraoptic Nucleus• vasopressin & oxytocinvasopressin & oxytocin

5.5. Suprachiasmatic Nucleus:Suprachiasmatic Nucleus:• ACTH & gonadotrophinACTH & gonadotrophin


Efferent Output:Efferent Output:1.1. Autonomic response:Autonomic response:

1.1. Hormonal response:Hormonal response:• Hypothalamic – anterior pituitary controlHypothalamic – anterior pituitary control• Posterior pituitary controlPosterior pituitary control• Autonomic controlAutonomic control

2.2. Local tissue response:Local tissue response:

Hormone Response to InjuryHormone Response to InjuryHypothalamic regulationHypothalamic regulation

1.1. CRHCRH2.2. TRHTRH3.3. GHRHGHRH4.4. LHRHLHRH

Anterior Pituitary regulationAnterior Pituitary regulation1.1. ACTH – cortisolACTH – cortisol2.2. TSH – T3/T4TSH – T3/T43.3. GHGH4.4. GonadotrophinsGonadotrophins5.5. Sex hormonesSex hormones6.6. Insulin-like growth factorInsulin-like growth factor7.7. SomatostatinSomatostatin8.8. ProlactinProlactin9.9. EndorphinsEndorphins

Posterior Pituitary Posterior Pituitary regulationregulation1.1. VasopressinVasopressin2.2. OxytocinOxytocin

Autonomic SystemAutonomic System1.1. NE / ENE / E2.2. AldosteroneAldosterone3.3. Renin-angiotensin systemRenin-angiotensin system4.4. InsulinInsulin5.5. GlucagonGlucagon6.6. EnkephalinsEnkephalins

HORMONES UNDER ANTERIOR PITUITARYHORMONES UNDER ANTERIOR PITUITARYREGULATIONREGULATION1.1. CRF – ACTH – Cortisol:CRF – ACTH – Cortisol:

a.a. (+) CRF(+) CRF – – pain, fear, anxiety, pain, fear, anxiety, angiotensin II, serotonin, angiotensin II, serotonin, acetylcholine & interleukin 1/6acetylcholine & interleukin 1/6

a.a. ACTHACTH – – circardian signals is lost in injury due to pain, circardian signals is lost in injury due to pain, anxiety, anxiety, vasopressin, angiotensin II, E, vasopressin, angiotensin II, E,

NE, oxytocins & proinflammatory NE, oxytocins & proinflammatory cytokinescytokines

b.b. CortisolCortisol - - elevated in any types of injury, longest in burn elevated in any types of injury, longest in burn pts. (4wks). Actions in injury:pts. (4wks). Actions in injury:

b.b. potentiates the action of glucagon & E causing hyperglycemia.potentiates the action of glucagon & E causing hyperglycemia.c.c. favors gluconeogenesis; insulin resistance in muscles & adipose favors gluconeogenesis; insulin resistance in muscles & adipose

tissue.tissue.d.d. induces protein degradation in the skeletal muscle & releases induces protein degradation in the skeletal muscle & releases

lactate for hepatic gluconeogenesis lactate for hepatic gluconeogenesis e.e. potentiates release of FA, triglycerides & glycerol from adipose potentiates release of FA, triglycerides & glycerol from adipose

tissue for energy sourcetissue for energy source

1.1. CRF – ACTH – Cortisol:CRF – ACTH – Cortisol: Acute adrenal Insufficiency (AAI):Acute adrenal Insufficiency (AAI):

• Life threatening complicationLife threatening complication• Commonly due to adrenal suppression from exogenous Commonly due to adrenal suppression from exogenous

administration of glucocorticoidadministration of glucocorticoid• Manifestation:Manifestation:

1.1. weakness, n / v, fever & hypotensionweakness, n / v, fever & hypotension

2.2. Hypoglycemia (due to low gluconeogenesis)Hypoglycemia (due to low gluconeogenesis)

3.3. Hyponatremia & Hyperkalemia (impaired renal tubular Hyponatremia & Hyperkalemia (impaired renal tubular reabsorption – due to insufficient aldosterone) reabsorption – due to insufficient aldosterone)

Cortisol Cortisol is an effective immuno-suppressive agents:is an effective immuno-suppressive agents:1.1. Caused thymic involutionCaused thymic involution

2.2. Depressed cell mediated immune responseDepressed cell mediated immune response

3.3. Cause monocyte & neutrophil lose of intracellular bacterial Cause monocyte & neutrophil lose of intracellular bacterial killingkilling

4.4. It downregulates proinflammatory cytokines production (TNF It downregulates proinflammatory cytokines production (TNF alpha, IL-1, IL-6); and increases the production of anti-alpha, IL-1, IL-6); and increases the production of anti-inflammatory mediator IL-10.inflammatory mediator IL-10.

2.2. Growth Hormone:Growth Hormone: (+) GH is GHRF(+) GH is GHRF (-) GH is somatostatin(-) GH is somatostatin Anabolic for CHON; catabolic for CHO & lipidsAnabolic for CHON; catabolic for CHO & lipids Stimulatory:Stimulatory:

• Hypoglycemia, decrease ECV, decrease plasma FA & a.a., Hypoglycemia, decrease ECV, decrease plasma FA & a.a., exercise, STRESS and sleep.exercise, STRESS and sleep.

• Thyroxine, vasopressin, MSH, testosterone, estrogen and Thyroxine, vasopressin, MSH, testosterone, estrogen and alpha adrenergic stimulation.alpha adrenergic stimulation.

INSULIN like GROWTH FACTOR-1 INSULIN like GROWTH FACTOR-1 (Somatomedin C; IGF-1)(Somatomedin C; IGF-1)

1.1. Partially mediates CHON synthesis properties of GH after Partially mediates CHON synthesis properties of GH after injuryinjury

2.2. The The liverliver is the predominant source of IGF-1. is the predominant source of IGF-1.

3.3. Promotes a.a. incorporation & cellular proliferation and Promotes a.a. incorporation & cellular proliferation and attenuates proteolysis in skeletal muscle & liver.attenuates proteolysis in skeletal muscle & liver.

4.4. In injury: the effects of IGF-1 is inhibited by In injury: the effects of IGF-1 is inhibited by proinflammatory cytokines (TNF, IL-1 and IL-6). proinflammatory cytokines (TNF, IL-1 and IL-6). Resulting to (-) nitrogen balance.Resulting to (-) nitrogen balance.

3.3. Macrophage Inhibitory Factor:Macrophage Inhibitory Factor: Produced by:Produced by:

a.a. Anterior pituitary glandAnterior pituitary gland

b.b. T lymphocytes at the site of inflammation.T lymphocytes at the site of inflammation.

Actions:Actions:

a.a. A glucocorticoid antagonist (suppresses the A glucocorticoid antagonist (suppresses the immunosuppresive effects of cortisol).immunosuppresive effects of cortisol).

b.b. It is a proinflammatory mediator that potentiates gm (-) & (+) It is a proinflammatory mediator that potentiates gm (-) & (+) septic shock.septic shock.

4.4. Endogenous Opiods:Endogenous Opiods: Endorphins, enkephalinsEndorphins, enkephalins Elevated after injury & surgeryElevated after injury & surgery Endorphins ----> attenuate pain perceptions / hypotensionEndorphins ----> attenuate pain perceptions / hypotension

Enkephalins ----> HPN, decrease peristalsis and secretion of GITEnkephalins ----> HPN, decrease peristalsis and secretion of GIT

5.5. Thyroid Hormone (T4 / T3):Thyroid Hormone (T4 / T3): In injury:In injury:

a.a. Low T3Low T3

b.b. (-) TSH release(-) TSH release

c.c. Conversion of T4 – T3 in the target organs are impaired Conversion of T4 – T3 in the target organs are impaired due to cortisol. T4 is converted to an inactive T3 called rT3due to cortisol. T4 is converted to an inactive T3 called rT3

6.6. Gonadotrophins (LHRH/GnRH) & (FSH/LH):Gonadotrophins (LHRH/GnRH) & (FSH/LH): Injury, stress or severe illness ----> (-) GRH ----> (-) LH and Injury, stress or severe illness ----> (-) GRH ----> (-) LH and

(-) FSH ---> decrease estrogen and androgen secretions.(-) FSH ---> decrease estrogen and androgen secretions. Causes menstrual irregularities and decrease libido. Causes menstrual irregularities and decrease libido.

7.7. Prolactin:Prolactin: Produced by anterior pituitary gld and T lymphocytesProduced by anterior pituitary gld and T lymphocytes Elevated level after injury in adults not seen in childrenElevated level after injury in adults not seen in children Causes amenorrheaCauses amenorrhea

HORMONES OF AUTONOMIC SYSTEM:HORMONES OF AUTONOMIC SYSTEM:1.1. Catecholamines (E / NE):Catecholamines (E / NE):

Causes hypermetabolic state following severe injuryCauses hypermetabolic state following severe injury 3 – 4fold increase of E & NE in the plasma for 24 – 48 3 – 4fold increase of E & NE in the plasma for 24 – 48

hrs.hrs. Causes:Causes:

a.a. Promotes glycogenolysis, gluconeogenesis, Promotes glycogenolysis, gluconeogenesis, lipolysis and ketogenesis.lipolysis and ketogenesis.

b.b. Decreased insulin release & increase glucagon Decreased insulin release & increase glucagon secretion.secretion.

c.c. Peripherally, it increases lipolysis in adipose tissue Peripherally, it increases lipolysis in adipose tissue and induces insulin resistance in skeletal muscleand induces insulin resistance in skeletal muscle

d.d. It inhibit the release of aldosterone.It inhibit the release of aldosterone.e.e. Immune function: -- enhances neutrophilia and Immune function: -- enhances neutrophilia and

lymphocytosislymphocytosis

2.2. Aldosterone (Mineralocorticoid):Aldosterone (Mineralocorticoid): Released by adrenal zona glomerulosaReleased by adrenal zona glomerulosa Release is caused by:Release is caused by:

1.1. Angiotensin IIAngiotensin II

2.2. HyperkalemiaHyperkalemia

3.3. Aldosterone stimulating factor (ASF) in pituitaryAldosterone stimulating factor (ASF) in pituitary

4.4. ACTH (is the most potent stimulant).ACTH (is the most potent stimulant). Major function is to maintain intravascular volume Major function is to maintain intravascular volume

by conserving Na & eliminating potassium and H+ in by conserving Na & eliminating potassium and H+ in the early distal convoluted tubules of nephronthe early distal convoluted tubules of nephron

3.3. Renin – Angiotensin:Renin – Angiotensin: Renin in Juxtaglomerular apparatus is released by:Renin in Juxtaglomerular apparatus is released by:

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

concentration.concentration.

Action of angiotensin II:Action of angiotensin II:a.a. VasoconstrictorVasoconstrictorb.b. (+) aldosterone(+) aldosteronec.c. (+) ADH(+) ADHd.d. (+) E(+) Ee.e. Increase heart rate and contractilityIncrease heart rate and contractility

4.4. Glucagon:Glucagon: alpha islet cellalpha islet cell catabolic rolecatabolic role elevated release after injuryelevated release after injury

5.5. Insulin:Insulin: Inhibit its release in injury:Inhibit its release in injury:

a.a. CatecholamineCatecholamineb.b. GlucagonGlucagonc.c. SomatostatinSomatostatind.d. Beta endorphinsBeta endorphinse.e. IL-1IL-1

Hormones Under Posterior Pituitary Hormones Under Posterior Pituitary Regulation:Regulation:

1.1. Vasopressin / ADH / Arginine Vasopressin / ADH / Arginine Vasopressin (AVP):Vasopressin (AVP):

CausesCauses

a.a. readsorption of H2O in DCTreadsorption of H2O in DCTb.b. Vasoconstriction peripherallyVasoconstriction peripherallyc.c. Stimulates hepatic glycogenolysis & Stimulates hepatic glycogenolysis &

gluconeogenesisgluconeogenesis Elevated plasma osmolality is its major Elevated plasma osmolality is its major

stimulus:stimulus: Location of osmoreceptors: Location of osmoreceptors: hypothalamus, hypothalamus,

portal circulationportal circulation

Hormones Under Posterior Pituitary Hormones Under Posterior Pituitary Regulation:Regulation:

1.1. Vasopressin / ADH / Arginine Vasopressin / ADH / Arginine Vasopressin (AVP):Vasopressin (AVP):

Its release also happens in 10% loss of ECV Its release also happens in 10% loss of ECV stimulating the baroreceptor in the left atriumstimulating the baroreceptor in the left atrium

Other stimulus:Other stimulus:1.1. PAINPAIN2.2. Beta adrenergicBeta adrenergic3.3. Angiotensin IIAngiotensin II4.4. OpiodsOpiods5.5. Elevated glucoseElevated glucose

2.2. Oxytocin:Oxytocin: Its release caused by SUCKING the nippleIts release caused by SUCKING the nipple Stimulates contraction of mammary gland Stimulates contraction of mammary gland

and uterus during parturitionand uterus during parturition No known function in malesNo known function in males Role in injury is unknownRole in injury is unknown

Mediators of InflammationMediators of Inflammation1.1. Cytokines:Cytokines:

Most potent mediator of the inflammatory responseMost potent mediator of the inflammatory response Eradicates invading microorganism and promotes Eradicates invading microorganism and promotes

wound healingwound healing Overwhelming productions of proinflammatory Overwhelming productions of proinflammatory

cytokines can cause:cytokines can cause:a.a. Hemodynamic instability (septic shock)Hemodynamic instability (septic shock)

b.b. Metabolic derangement (muscle wasting)Metabolic derangement (muscle wasting)

Can exaggerate to multiple organ failure and death.Can exaggerate to multiple organ failure and death. Inappropriate anti-inflammatory mediator release Inappropriate anti-inflammatory mediator release

can lead to immunocompromised and susceptible to can lead to immunocompromised and susceptible to overwhelming infection.overwhelming infection.

Mediators of InflammationMediators of Inflammation2.2. Heat Shock Heat Shock

Proteins:Proteins: Intracellular protein Intracellular protein

modifiers and modifiers and transporters that transporters that protect cells from the protect cells from the deleterious effects of deleterious effects of traumatic stress.traumatic stress.

The following induced The following induced its production:its production:

a.a. HypoxiaHypoxiab.b. TraumaTraumac.c. Heavy metalsHeavy metalsd.d. Local traumaLocal traumae.e. HemorrhageHemorrhage

Mediators of InflammationMediators of Inflammation3.3. Reactive Oxygen Metabolites:Reactive Oxygen Metabolites:

Oxygen radicals Oxygen radicals are produced by reduction of are produced by reduction of oxygen to superoxide anion, and further oxygen to superoxide anion, and further metabolized to form metabolized to form H2O2 & hydroxyl H2O2 & hydroxyl radicalsradicals

Causes injury by oxidation of unsaturated fatty Causes injury by oxidation of unsaturated fatty acids w/in cell membranes.acids w/in cell membranes.

Activated leukocytes Activated leukocytes are potent generators are potent generators for reactive oxygen metabolites.for reactive oxygen metabolites.

Cells are protected from this metabolite by Cells are protected from this metabolite by oxygen scavengers: oxygen scavengers: GLUTATHIONE GLUTATHIONE & & CATALASES.CATALASES.

Mediators of InflammationMediators of Inflammation

4.4. Eicosanoids:Eicosanoids: Are oxidation derivatives of Are oxidation derivatives of

membrane membrane phospholipid phospholipid arachidonic acidsarachidonic acids

Secreted by nucleated cells, Secreted by nucleated cells, except lymphocytesexcept lymphocytes

Not stored w/in cells but are Not stored w/in cells but are synthesized rapidly upon synthesized rapidly upon stimulation by hypoxic stimulation by hypoxic injury, tissue injury, injury, tissue injury, endotoxin, NE, vasopressin endotoxin, NE, vasopressin angiotensin II, bradykinin, angiotensin II, bradykinin, serotonin, acetylcholine, serotonin, acetylcholine, cytokines and histamine cytokines and histamine


4.4. Eicosanoids:Eicosanoids:Actions:Actions:a.a. PGEPGE22 increases fluid leakage increases fluid leakage

from bld vessels, inhibit from bld vessels, inhibit gluconeogenesis and gluconeogenesis and hormone stimulated lipolysis.hormone stimulated lipolysis.

b.b. LeukotrienesLeukotrienes are 1000x are 1000x more potent than histamine more potent than histamine promoting capillary leakage, promoting capillary leakage, vasoconstriction, vasoconstriction, bronchoconstriction, bronchoconstriction, neutrophil activation.neutrophil activation.

c.c. Products of Products of cyclooxygenase cyclooxygenase inhibit inhibit pancreatic beta cell release pancreatic beta cell release of insulin.of insulin.

Mediators of InflammationMediators of Inflammation5.5. Kallikrein-Kinin System:Kallikrein-Kinin System:

a.a. Bradykinin:Bradykinin:• potent vasodilators potent vasodilators • Release is caused by hypoxic and ischemic Release is caused by hypoxic and ischemic

injuryinjury

b.b. Kinins:Kinins: • increase capillary permeability and tissue edema, increase capillary permeability and tissue edema, • evoke pain, evoke pain, • Inhibit gluconeogenesis Inhibit gluconeogenesis • increase bronchoconstriction. increase bronchoconstriction. • increase renal vasodilation and reduces renal increase renal vasodilation and reduces renal

perfusion pressure ----> (+) renin-angiotensin perfusion pressure ----> (+) renin-angiotensin system.system.


6.6. Serotonin:Serotonin: neurotransmitter (5hydrohytryptamine)neurotransmitter (5hydrohytryptamine) tryptophan derivative tryptophan derivative found in chromaffin found in chromaffin

cells of the intestine (carcinoid tumors).cells of the intestine (carcinoid tumors). Vasoconstrictions, bronchoconstriction & Vasoconstrictions, bronchoconstriction &

platelet aggregationsplatelet aggregations myocardial chronotrope and inotropemyocardial chronotrope and inotrope

Mediators of InflammationMediators of Inflammation7.7. Histamine:Histamine:

Derived from Derived from histidinehistidine Stored in neurons, skin, gastric mucosa, Stored in neurons, skin, gastric mucosa,

mast cells basophils and plateletsmast cells basophils and platelets Released is activated by increased Released is activated by increased

calcium levels.calcium levels.

2 receptors:2 receptors:a.a. H1 – stimulates bronchoconstriction, H1 – stimulates bronchoconstriction,

intestinal motility, and myocardial intestinal motility, and myocardial contractilitycontractility

b.b. H2 – inhibits histamine releaseH2 – inhibits histamine release

Mediators of InflammationMediators of Inflammation7.7. Histamine:Histamine:

Both H1 & H2 receptor activation causes:Both H1 & H2 receptor activation causes:a.a. HypotensionHypotensionb.b. Peripheral pooling of bloodPeripheral pooling of bloodc.c. Increase capillary permeabilityIncrease capillary permeabilityd.d. Decrease venous returnDecrease venous returne.e. Myocardial failureMyocardial failure

Elevated in cases of hemorrhagic shock, Elevated in cases of hemorrhagic shock, trauma, thermal injury, endotoxemia and trauma, thermal injury, endotoxemia and sepsis.sepsis.

CytokinesCytokines Usually secreted by immunocytes & other cellsUsually secreted by immunocytes & other cells

Indespensible to tissue healing and immune response Indespensible to tissue healing and immune response generated against microbial invasiongenerated against microbial invasion

Are not stored as preformed molecules and it’s activity is Are not stored as preformed molecules and it’s activity is primarily exerted locally w/ cell to cell interactionprimarily exerted locally w/ cell to cell interaction

Their rapid appearance after injury is due to active Their rapid appearance after injury is due to active transcription and translation by the injured or stimulated transcription and translation by the injured or stimulated cells.cells.

Direct the inflammatory response to infection, injury and Direct the inflammatory response to infection, injury and actively promote wound healingactively promote wound healing

CYTOKINESCYTOKINES

1.1. TNF (Tumor Necrosis Factor):TNF (Tumor Necrosis Factor): Earliest & most potent mediatorsEarliest & most potent mediators Monocytes/macrophage and TcellsMonocytes/macrophage and Tcells Actions:Actions:

1.1. Major inducer muscle catabolism & cachexia Major inducer muscle catabolism & cachexia during stressduring stress

2.2. Coagulation activationCoagulation activation

3.3. Releases prostaglandin E2, platelet activating Releases prostaglandin E2, platelet activating factor (PAF), glucocorticoid and eicosanoidsfactor (PAF), glucocorticoid and eicosanoids

4.4. Initiates of hemodynamic decompensation.Initiates of hemodynamic decompensation.

CYTOKINESCYTOKINES

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

a.a. Induces febrile Induces febrile response to injury by stimulating response to injury by stimulating prostaglandin to anterior hypothalamus.prostaglandin to anterior hypothalamus.

b.b. Attenuated pain perception Attenuated pain perception by promoting by promoting release of beta-endorphins from the pituitary gld.release of beta-endorphins from the pituitary gld.

Endogenous IL-1 receptor antagonist Endogenous IL-1 receptor antagonist (IL-1ra) are (IL-1ra) are also released during injury to auto-regulate IL-1.also released during injury to auto-regulate IL-1.

CYTOKINESCYTOKINES

3.3. Interleukin-2:Interleukin-2: Promoter of T-lymphocyte proliferation, Promoter of T-lymphocyte proliferation,

immunoglobulin production & gut immunoglobulin production & gut barrier integrity.barrier integrity.

CYTOKINESCYTOKINES4.4. Interleukin-4 (IL-4):Interleukin-4 (IL-4):

Produced by activate T-helper lymphocyte.Produced by activate T-helper lymphocyte. Induces B lymphocyte to produce IgG & IgE Induces B lymphocyte to produce IgG & IgE

impt. for allergy and anthelmintic responses.impt. for allergy and anthelmintic responses. Potent anti-inflammatory propertiesPotent anti-inflammatory properties, it , it

downgrades the effects of:downgrades the effects of:a.a. IL-1IL-1b.b. TNF-alphaTNF-alphac.c. IL-6IL-6d.d. IL-8IL-8e.e. Increases macrophage susceptibility to Increases macrophage susceptibility to

the anti-inflammatory effects of the anti-inflammatory effects of glucocorticoidglucocorticoid


Produced by all cells & tissuesProduced by all cells & tissues Fnx:Fnx:

a.a. It It induces neutrophil activation induces neutrophil activation and and delay it’s disposal leading to the cells delay it’s disposal leading to the cells prolonged injurious effectprolonged injurious effect

b.b. It can also It can also attenuate TNF & IL-1 attenuate TNF & IL-1 by by promoting the release of soluble tumor promoting the release of soluble tumor necrosis factor receptors and IL-1 necrosis factor receptors and IL-1 receptor antagonists.receptor antagonists.

CYTOKINESCYTOKINES

6.6. Interleukin-8 (IL-8):Interleukin-8 (IL-8): Activity is similar to IL-6Activity is similar to IL-6 Biomarker for the risk of multiple organ Biomarker for the risk of multiple organ

failurefailure Does not produced hemodynamic instability Does not produced hemodynamic instability

but is a chemoattractant and activator of but is a chemoattractant and activator of neutrophilneutrophil

CYTOKINESCYTOKINES

6.6. Interleukin-10 (IL-10):Interleukin-10 (IL-10): It reduces TNF-alphaIt reduces TNF-alpha Attenuate systemic inflammatory Attenuate systemic inflammatory

response response and reduces mortality during and reduces mortality during septic peritonitisseptic peritonitis

Associated w/ increased bacterial load & Associated w/ increased bacterial load & mortalitymortality

CYTOKINESCYTOKINES

10.10. Interleukin-12 (IL-12):Interleukin-12 (IL-12): Primary role in cell-mediated immunity & Primary role in cell-mediated immunity &

promotes differentiation of Tpromotes differentiation of THH1 cells.1 cells. Inducing an inflammatory response for Inducing an inflammatory response for

48hrs, independently from TNF & IL-1.48hrs, independently from TNF & IL-1. Promotes neutrophil & coagulation activationPromotes neutrophil & coagulation activation Toxicity is synergistic w/ IL-2Toxicity is synergistic w/ IL-2..

CYTOKINESCYTOKINES

11.11. Interleukin-13 (IL-13):Interleukin-13 (IL-13): Structural & functional similarities w/ IL-4Structural & functional similarities w/ IL-4 Modulate macrophage functionModulate macrophage function Inhibit nitric oxide production & the Inhibit nitric oxide production & the

expression of proinflammatory cytokines expression of proinflammatory cytokines and enhance production of IL-1raand enhance production of IL-1ra

It attenuates leukocyte interaction w/ It attenuates leukocyte interaction w/ activated endothelial surfacesactivated endothelial surfaces


Potent autocrine regulatory properties.Potent autocrine regulatory properties. Possess similar bioactivity in promoting Possess similar bioactivity in promoting

lymphocyte activation & proliferationlymphocyte activation & proliferation Induces IL-8 productionInduces IL-8 production..

13.13. Interleukin-18 (IL-18):Interleukin-18 (IL-18): Formerly interferon (IFN)-y-inducing factorFormerly interferon (IFN)-y-inducing factor Proinflammatory cytokineProinflammatory cytokine Structurally similar to IL-1beta & functionally Structurally similar to IL-1beta & functionally

similar to IL-12.similar to IL-12.

CYTOKINESCYTOKINES14.14. Interferon-y:Interferon-y:

Produced by Helper T lymphocytes when Produced by Helper T lymphocytes when activated by bacterial antigens, IL-2, IL-12, activated by bacterial antigens, IL-2, IL-12, IL-18IL-18

Can also induce production of IL-2, IL-12, Can also induce production of IL-2, IL-12, IL-18 IL-18

Elevated for as long as 8 days.Elevated for as long as 8 days. Can activate circulating and tissue Can activate circulating and tissue

macrophage macrophage Alveolar macrophage activation may induce Alveolar macrophage activation may induce

acute lung inflammation after major surgery acute lung inflammation after major surgery or trauma.or trauma.

CYTOKINESCYTOKINES

15.15. Granuloctye-Macrophage Colony-Granuloctye-Macrophage Colony-Stimulating Factor (GMC-SF):Stimulating Factor (GMC-SF):

Delays apoptosis Delays apoptosis of macrophages and of macrophages and neutrophils; neutrophils; contribute to organ injury contribute to organ injury (ARDS)(ARDS)

Promote maturation and recruitment of Promote maturation and recruitment of functional leukocytes needed for normal functional leukocytes needed for normal inflammatory cytokine response & potentially inflammatory cytokine response & potentially in wound healing.in wound healing.

Cell-Mediated Inflammatory Cell-Mediated Inflammatory ResponseResponse

1.1. Platelets:Platelets: Clot formed at the site of injury releases Clot formed at the site of injury releases

inflammatory mediators w/c serves as the inflammatory mediators w/c serves as the principal chemo-attractant for neutrophils principal chemo-attractant for neutrophils and monocytes.and monocytes.

Migration of platelets & neutrophils through Migration of platelets & neutrophils through the vascular endothelium occurs w/in 3 hrs the vascular endothelium occurs w/in 3 hrs of injury and mediated by:of injury and mediated by:

a.a. SerotoninSerotonin

b.b. Platelet-activating factorPlatelet-activating factor

c.c. Prostaglandin E2Prostaglandin E2


2.2. Lymphocytes & T-Lymphocytes & T-cell Immunity:cell Immunity:

Injury associated w/ Injury associated w/ Acute impairment of Acute impairment of cell-mediated cell-mediated immunity and immunity and macrophage functmacrophage functionion

2 subgroups of T-2 subgroups of T-helper lymphocytes:helper lymphocytes:

a.a. TTHH11

b.b. TTHH22


3.3. Eosinophils:Eosinophils: Migrate to inflammed endothelium and release Migrate to inflammed endothelium and release

cytoplasmic granules that are cytotoxiccytoplasmic granules that are cytotoxic It preferentially migrate to sites of parasitic infection It preferentially migrate to sites of parasitic infection

and allergyand allergy Resides in GIT, lung and genitourinary tissuesResides in GIT, lung and genitourinary tissues Major activators:Major activators:

a.a. IL-3IL-3

b.b. IL-5IL-5

c.c. Platelet-activating factorPlatelet-activating factor

d.d. Complement anaphylatoxins C3a and C5aComplement anaphylatoxins C3a and C5a


4.4. Mast Cells:Mast Cells: When activated it produce:When activated it produce:

a.a. HistamineHistamineb.b. Cytokines (IL-3, IL4, IL-5, IL-6, IL-10, IL-13, IL-14 Cytokines (IL-3, IL4, IL-5, IL-6, IL-10, IL-13, IL-14

& migration-inhibitory factor (MIF).& migration-inhibitory factor (MIF).c.c. EicosanoidsEicosanoidsd.d. ProteasesProteasese.e. ChemokinesChemokines


4.4. Mast Cells:Mast Cells: Immediate results:Immediate results:

a.a. VasodilationVasodilationb.b. Recruitment of other immunocytesRecruitment of other immunocytesc.c. Capillary leakageCapillary leakage

TNF-alpha secreted rapidly by this cell TNF-alpha secreted rapidly by this cell bec. of its abundant sourcebec. of its abundant source


5.5. Monocytes:Monocytes: There is down regulation in monocyte and There is down regulation in monocyte and

neutrophil TNFR expressionneutrophil TNFR expression In none surviving pts w/ severe sepsis and failed to In none surviving pts w/ severe sepsis and failed to

recover, an immediate reduction in monocyte recover, an immediate reduction in monocyte surface TNFR expression was observed, while surface TNFR expression was observed, while surviving pts have normal or near normal receptor surviving pts have normal or near normal receptor levels levels

6.6. Neutrophils:Neutrophils: Inflammatory mediators from site of injury induces Inflammatory mediators from site of injury induces

neutrophil adherence to the injured tissue.neutrophil adherence to the injured tissue. It’s function is mediated by vast array of intracellular It’s function is mediated by vast array of intracellular

granules that are chemotactic or cytotoxic to local granules that are chemotactic or cytotoxic to local tissue & invading microorganisms.tissue & invading microorganisms.

Endothelium-Mediated InjuryEndothelium-Mediated Injury

1.1. Neutrophil-Endothelium Interaction:Neutrophil-Endothelium Interaction: Inc. vascular permeability during inflammation is Inc. vascular permeability during inflammation is

intended to facilitate O2 delivery and immunocyte intended to facilitate O2 delivery and immunocyte migration to the site of injury.migration to the site of injury.

However accumulation & infiltration of leukocytes However accumulation & infiltration of leukocytes (neutrophil) contribute to the cytotoxicity of vital (neutrophil) contribute to the cytotoxicity of vital tissue ---> MOF.tissue ---> MOF.

Ischemia/reperfusion injury potentiates this Ischemia/reperfusion injury potentiates this response by:response by:

a.a. unleashing oxygen metabolitesunleashing oxygen metabolitesb.b. Lysosomal enzymes that degrade tissue basal membranesLysosomal enzymes that degrade tissue basal membranesc.c. Cause microvascular thrombosisCause microvascular thrombosisd.d. Activate myeloperoxidases.Activate myeloperoxidases.

Endothelium-Mediated InjuryEndothelium-Mediated Injury

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

Endothelium-Mediated InjuryEndothelium-Mediated Injury2.2. Nitric Oxide:Nitric Oxide:

Formed from oxidation of L-arginineFormed from oxidation of L-arginine Derived from endothelial surfacesDerived from endothelial surfaces Cells that produces this subs:Cells that produces this subs:

a.a. NeutrophilNeutrophilb.b. monocytesmonocytesc.c. Renal cellsRenal cellsd.d. Kupffer cellsKupffer cellse.e. Cerebellar neuronsCerebellar neurons

Action:Action:

a.a. Maintain normal smooth muscle relaxationMaintain normal smooth muscle relaxationb.b. Reduce thrombosis by reducing platelet Reduce thrombosis by reducing platelet

adhesions and aggregationadhesions and aggregationc.c. Mediates protein synthesis in hepatocyteMediates protein synthesis in hepatocyte

Endothelium-Mediated InjuryEndothelium-Mediated Injury3.3. Prostacyclin:Prostacyclin:

Induces vaso-relaxation and platelet deactivation by Induces vaso-relaxation and platelet deactivation by increasing cAMPincreasing cAMP

3.3. Endothelins:Endothelins:Formed by vascular endothelial cells in response to:Formed by vascular endothelial cells in response to:

a.a. InjuryInjuryb.b. ThrombinThrombinc.c. Transforming growth factor-B (TGF-B)Transforming growth factor-B (TGF-B)d.d. IL-1IL-1e.e. Angiotensin IIAngiotensin IIf.f. VasopressinVasopressing.g. CatecholamineCatecholamineh.h. AnoxiaAnoxia

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

Endothelium-Mediated InjuryEndothelium-Mediated Injury5.5. Platelet-Activating Factor:Platelet-Activating Factor:

Released by neutrophils, platelets, mast cells and Released by neutrophils, platelets, mast cells and monocytesmonocytes

It activate neutrophils and platelets and increase It activate neutrophils and platelets and increase vascular permeability.vascular permeability.

6.6. Atrial Natriuretic Peptides:Atrial Natriuretic Peptides: Released by atrial tissue, gut, kidney, brain, adrenal Released by atrial tissue, gut, kidney, brain, adrenal

glds and endotheliumglds and endothelium Actions:Actions:

a.a. Vasodilator and induce fluid and electrolyte excretionVasodilator and induce fluid and electrolyte excretion

b.b. Inhibits aldosterone secretionInhibits aldosterone secretion

c.c. Prevent reabsorption of sodiumPrevent reabsorption of sodium

END OF END OF FIRST PARTFIRST PART

Metabolic Changes and Metabolic Changes and Nutritional Management Nutritional Management

of Surgical Patientsof Surgical Patients

James Taclin C. Banez, MD, FPSGS, James Taclin C. Banez, MD, FPSGS, FPCSFPCS

Majority of surgical patients:Majority of surgical patients: well nourished / healthywell nourished / healthy uncomplicated major surgical procedureuncomplicated major surgical procedure has sufficient fuel reservehas sufficient fuel reserve can withstand brief period of catabolic insult can withstand brief period of catabolic insult

and starvation of 7 daysand starvation of 7 days Postoperatively:Postoperatively:

• can resume normal oral intakecan resume normal oral intake• supplemental diet is not neededsupplemental diet is not needed

Surgical Patients that Needs Surgical Patients that Needs Nutritional SupportNutritional Support

To shorten the postoperative recovery To shorten the postoperative recovery phase and minimize the number of phase and minimize the number of complications:complications:

1.1. Chronically debilitated from their diseases or Chronically debilitated from their diseases or malnutrition. malnutrition.

2.2. Suffered severe trauma, sepsis or surgical Suffered severe trauma, sepsis or surgical complicationscomplications

Metabolic Changes in Surgical PatientsMetabolic Changes in Surgical Patients

Metabolic events brought about by Metabolic events brought about by STIMULISTIMULI::

1.1. InjuryInjury

2.2. StarvationStarvation

Metabolic response is directed to restore:Metabolic response is directed to restore:1.1. HomeostasisHomeostasis

2.2. RepairRepair

Metabolic Response to Metabolic Response to StarvationStarvation

HYPOGLYCEMIAHYPOGLYCEMIA – is primary stimulus – is primary stimulus Hormonal Changes: increase Hormonal Changes: increase cortisol, catecholamines, cortisol, catecholamines,

glucagon, growth hormonesglucagon, growth hormones Primary gluconeogenic precursors by the liver & kidney:Primary gluconeogenic precursors by the liver & kidney:

a.a. lactate lactate b. b. glycerol glycerol c. c. amino acid (alanine & glutamine)amino acid (alanine & glutamine)

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

Protein catabolism for gluconeogenesis primarily comes Protein catabolism for gluconeogenesis primarily comes from from SKELETALSKELETAL muscle, but in pure starvation other muscle, but in pure starvation other organs are involvedorgans are involved

In liver. CHON loss is selective; spare enzymes for In liver. CHON loss is selective; spare enzymes for gluconeogenesis and lipolysis.gluconeogenesis and lipolysis.

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

Rapid proteolysis of body CHON cannot proceed at 75 Rapid proteolysis of body CHON cannot proceed at 75 g/day for long, or else patient will die immediately g/day for long, or else patient will die immediately RANDLE EFFECT.RANDLE EFFECT. decrease urinary excretion of nitrogen 2 – 4 gm/day due decrease urinary excretion of nitrogen 2 – 4 gm/day due

to keto-adaptation of the brainto keto-adaptation of the brain decrease protein degeneration and decrease protein degeneration and major source of major source of

energy is FAT (90%)energy is FAT (90%)

Metabolism of Metabolism of Injured PatientInjured Patient

PHASES:PHASES:1.1. Catabolic phaseCatabolic phase (Ebb, Adrenergic-(Ebb, Adrenergic-

Corticoid):Corticoid): immediately following surgery or traumaimmediately following surgery or trauma characterized w/ hyperglycemia, increase characterized w/ hyperglycemia, increase

secretion of urinary nitrogen beyond the level secretion of urinary nitrogen beyond the level of starvationof starvation

caused by increase caused by increase glucagon, glucagon, glucocorticoid, catecholamines and glucocorticoid, catecholamines and decrease insulindecrease insulin

tries to restore circulatory volume and tissue tries to restore circulatory volume and tissue perfusionperfusion

Metabolism of Injured PatientMetabolism of Injured PatientPHASES:PHASES:

2.2. Early anabolic phase Early anabolic phase (flow, corticoid-(flow, corticoid-withdrawal):withdrawal):

tissue perfusion has been restored, may last for days tissue perfusion has been restored, may last for days to months depending on:to months depending on:

a.a. severity of injuryseverity of injury

b.b. previous healthprevious health

c.c. medical interventionmedical intervention sharp decline in nitrogen excretionsharp decline in nitrogen excretion nitrogen balance is positivenitrogen balance is positive (4g/day) indicating (4g/day) indicating

synthesis of CHON and there is a rapid and synthesis of CHON and there is a rapid and progressive gain in weight and muscular strengthprogressive gain in weight and muscular strength

Metabolism of Injured PatientMetabolism of Injured Patient

PHASES:PHASES:

3.3. Late anabolic phase:Late anabolic phase: several months after injuryseveral months after injury occurs once volume deficit have been occurs once volume deficit have been

restoredrestored slower re-accumulation of CHONslower re-accumulation of CHON re-accumulation of body fatre-accumulation of body fat

Metabolism of Injured PatientMetabolism of Injured PatientCarbohydrate Metabolism in Injured Carbohydrate Metabolism in Injured

Patient:Patient:HyperglycemiaHyperglycemia = proportional to the severity of = proportional to the severity of

injuryinjury Importance:Importance:

1.1. Homeostatic significanceHomeostatic significance2.2. Ready source of energy to the brainReady source of energy to the brain3.3. Adequate deliveryAdequate delivery

Caused by:Caused by:• Increased catecholamine (primarily), cortisol, Increased catecholamine (primarily), cortisol,

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


Carbohydrate Metabolism:Carbohydrate Metabolism:Hyperglycemia:Hyperglycemia:

Caused by:Caused by:• Increased catecholamine (primarily), cortisol, Increased catecholamine (primarily), cortisol,

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

• Gluconeogenesis in liver and kidney and Gluconeogenesis in liver and kidney and impaired peripheral uptake of glucoseimpaired peripheral uptake of glucose

Metabolism of Injured PatientMetabolism of Injured PatientCarbohydrate Metabolism:Carbohydrate Metabolism:Hyperglycemia:Hyperglycemia:

Insulin resistance:Insulin resistance:• During the Ebb phase there is reduction in beta cell During the Ebb phase there is reduction in beta cell

sensitivity to glucose due to sensitivity to glucose due to Catecholamine, Catecholamine, somatostatin and reduced pancreatic blood flowsomatostatin and reduced pancreatic blood flow

• Resistance to exogenous administrationResistance to exogenous administration on on insulin in both EBB and early FLOW phasesinsulin in both EBB and early FLOW phases

• In middle and late Flow phase, beta cell sensitivity In middle and late Flow phase, beta cell sensitivity return to normal and it’s level is higher, but return to normal and it’s level is higher, but hyperglycemia persist because of continuous hyperglycemia persist because of continuous gluconeogenesisgluconeogenesis


Carbohydrate Metabolism:Carbohydrate Metabolism: Glucose metabolism in wounded tissueGlucose metabolism in wounded tissue::

Increase glucose uptake and Increase glucose uptake and lactatelactate production production because of anaerobic glycolysis due to local because of anaerobic glycolysis due to local tissue hypoxiatissue hypoxia

(+) insulin insensitivity(+) insulin insensitivity


Lipid metabolism:Lipid metabolism: primary source of energyprimary source of energy Best stimulus for hormone-sensitive lipase is Best stimulus for hormone-sensitive lipase is

CATECHOLAMINECATECHOLAMINE RANDLE EFFECTRANDLE EFFECT is not present is not present

Metabolism of Injured PatientMetabolism of Injured PatientProtein Metabolism:Protein Metabolism:

Nitrogen urine excretion 30-50g/day due to Nitrogen urine excretion 30-50g/day due to proteolysisproteolysis; ; 20% utilized for energy (calories)20% utilized for energy (calories) the rest for the rest for gluconeogenesisgluconeogenesis by liver and kidney (cortisol, by liver and kidney (cortisol, glucagon, catecholamine).glucagon, catecholamine).

Primary source of protein is the Primary source of protein is the skeletal muscleskeletal muscle and and the visceral organs are spared.the visceral organs are spared.

KetoadaptationKetoadaptation is is inhibitedinhibited ----> gluconeogenesis ----> gluconeogenesis persist ---> proteolysis persist persist ---> proteolysis persist (INTERLEUKIN I).(INTERLEUKIN I).

The degree and duration (-) nitrogen balance is related The degree and duration (-) nitrogen balance is related to to severity of injuryseverity of injury. The net CHON catabolism depends . The net CHON catabolism depends on the on the age, sex and physical condition of the patientage, sex and physical condition of the patient (> (> in young, healthy and male) in young, healthy and male)

(-) nitrogen balance can be reduced by (-) nitrogen balance can be reduced by high caloric high caloric nitrogen supplement nitrogen supplement

Traumatized ManTraumatized Man

Injury of any type is associated with:Injury of any type is associated with:1.1. ImmobilizationImmobilization2.2. StarvationStarvation3.3. RepairRepair

the first two are associated with reduction in the first two are associated with reduction in energy requirement. While the third is energy requirement. While the third is associated w/ increase energy requirementassociated w/ increase energy requirement

The amount of energy produced in injured pt. The amount of energy produced in injured pt. is not optimum, to supply necessary energy is not optimum, to supply necessary energy for the repair due to:for the repair due to:

1.1. reduced or absent nutritional intakereduced or absent nutritional intake2.2. significant reduction of energy charge and significant reduction of energy charge and

ATP content during shock, hypoxia, sepsis, ATP content during shock, hypoxia, sepsis, ischemia and wound -ischemia and wound - anaerobic anaerobic metabolismmetabolism

REE (Resting energy expenditure) by REE (Resting energy expenditure) by Harris and Benedict:Harris and Benedict:

(MEN)(MEN) 66.47 + 13.75 (W) + 5.0 (H) – 6.76 (A) 66.47 + 13.75 (W) + 5.0 (H) – 6.76 (A)

= = Kcal/dayKcal/day

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

= = Kcal/dayKcal/day

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

systemic response to injury

Education