ENDOCRINE &

METABOLIC RESPONSE
TO INJURY
Mete Duren, MD
STRESS FACTORS
 SURGERY
 BURNS-HYPERTHERMIA
 VASCULAR OCCLUSIONS
 DEHYDRATATION
 ANESTHESIA
 PAIN
 PSYCHOLOGIC EMOTIONS
MEDIATORS
 HORMONES
 CYTOKINS
 ENDOTHELIAL PRODUCTS
 INTRACELLULAR PRODUCTS
 TRAUMA
HYPOVOLEMIC SHOCK
ASCENDING LYMBIC SYMPATH. MACROPHA
RETICULAR SYSTEM NERVOUS GES
FORMATION SYSTEM
RENIN THALAMU CATECHO IL-1
HYPO S LAMINES
ANGIOTENSIN 2 ANT. POST. TACHYCARDIA INCR.TEMP
PITUITARY PITUATARY

ACTH-GH- ADH TACHYPNOEA INCR.WBC

PRL

CORTISOL& VASOCONSTR INCR.IgG

ALDOSTERON
HORMONES (POSTTRAUMATIC)
INCREASED DECREASED
 GH  INSULIN
 ACTH  IGF
 SOMATOSTATIN  FSH-LH
 DOPAMIN  ESTROGEN-PROGESTERON
 PROLACTIN  TESTOSTERON
 VASOPRESSIN  TSH
 RENIN-ANGIOTENSIN  T3-T4
 GLUCAGON
 HISTAMIN-SERETONIN
 KININES
 EIKOSANOIDS
 TNF
 BETAENDORPHIN
HORMONES CONTROLLED BY
ANT. PITUITARY
 CRH / ACTH
CRH released by paraventricular nuclei of
hypothalamus →ACTH by chromofob cells
of ant.pituitary → cortisol by adrenal cortex
 CRH / ACTH/CORTISOL levels are parallel
to the severity of the trauma
FACTORS INCREASING CRH
 PAIN
 FEAR
 ANXIETY
 EMOTION
 CYTOKINS
 ADH
 ANGIOTENSIN 2
 NEUROPEPTID
 SERETONIN
 ACETYLCHOLIN
FACTORS DECREASING CRH
 CORTISOL
 G-A-B-A
 SUBSTANCE P
 ATRIAL NATRIURETIC PEPTID
 ENDOGENOUS OPIODS
 ARGININ
HORMONES CONTROLLED BY
ANT. PITUITARY
 TRH/TSH
 TRH released by hypothalamus →TSH by
basophil cells of ant.pituitary → T3 & T4 by
thyroid
 Euthyroid sick syndrome: low T3 & T4- no
increase in TSH – increase in r T3-no
changes in free forms
HORMONES CONTROLLED BY
ANT. PITUITARY
 GHRH/ GH
 GH is increased after major surgery & gen.
anesthesia,
 Mobilizes fat stores, increases protein
synthesis and blood glucose level
 Direct stimulus&indirect stimulus by Insulin
like GF (IGF)
FACTORS INCREASING GH
 GHRH
 T4
 ACTH
 AVP/ADH
 MSH
 GLUCAGON
 SEX HORMONES
 EXERCISE
 SLEEP
 STRESS
 HYPOVOLEMIA
 HYPOGLISEMIA
 DECREASED FATTY ACIDS
 INCREASED AMINO ACIDS
FACTORS DECREASING GH
 HYPERGLISEMIA
 HYPERLIPIDEMIA
 SOMATOSTATIN
 BETA ADRENERGIC STIMULI
 CORTISOL
HORMONES CONTROLLED BY
ANT. PITUITARY
 GRH/ LH & FSH
 GRH released by hypothalamus →LH& FSH by
basophil cells of ant.pituitary
 Decreased by CRH, PRL, estrogen, progesteron
and androgen
 Decreased LH & FSH results in decrease of
estrogen and androgen
 Cause of posttraumatic loss of libido&menstruel
disorder
HORMONES CONTROLLED BY
ANT. PITUITARY
 PRL
 LHRH&GnRH, dopamine decrease PRL
synthesis in ant. Pituitary.
 CRH, TRH,GHRH, seretonin, VIP increse
PRL
 Posttraumatic increase in PRL causes
amenorrhea
HORMONES CONTROLLED BY
ANT. PITUITARY
 ENDOGENOUS OPIOIDS
 Increased after trauma
 Beta endorphins decrease pain, cause
hypotension by seretonin
 Enchefalins cause hypertension
 Both decrease GIS activity
HORMONES CONTROLLED BY
POST. PITUITARY
 AVP / ADH
 Secreted in ant. Pituitary, stored in post. Pituitary.
 Increase in plasma osmolality stimulates Na-sensitive-
osmoreceptors in hypothalamus →AVP increases
 Decrease of 10% of circulating blood volume →left atrial
tension receptors and chemoreceptors stimulated →increase
in AVP
 Atrial natriuretic factor ANF decreases AVP
 Trauma, major surgery increases AVP
 Inappropriate ADH secretion: characterized by decrease in
urinary production, increase in urinary concentration and
dilutional hyponatremia. (Plasma osm is below 275 mOsm/kg
urinary osm above 100 mOsm/kg)
HORMONES CONTROLLED BY
AUTONOMOUS NERVOUS S.
 Catecholamines: NE & E increase 3-4
times and stay increased for 1-2 days.
 NE by SNS, E by adrenal medulla
 NE &E increase gluconeogenesis and
lipolysis, thyroid hormones and renin
HORMONES CONTROLLED BY
AUTONOMOUS NERVOUS S.
 Aldosteron: secreted in z. Glomerulosa of
adrenal cortex
 Stimulated by angiotensin 2 and
hyperkalemia
 But most potent stimulator during trauma is
ACTH
 Protects intravascular volume by keeping
Na and causing loss of K and H ions
HORMONES CONTROLLED BY
AUTONOMOUS NERVOUS S.
 Renin-Angiotensin: secreted in juxtaglomerular
apparatus near afferent arteriols of the kidneys.
 Prorenin becomes renin by ACTH, glucagon,
Prostaglandins, K, Mg and Ca
 Increased during hypotension through
baroreceptors
 Renin causes change of angiotensinogen in
angiotensin 1, which becomes AT 2 in pulmonary
capillaries by converting enzyme.
 AT2 increases epinephrines, aldosteron and
vazopressin, it causes gluconeogenesis
HORMONES CONTROLLED BY
AUTONOMOUS NERVOUS S.
 Insulin: stimulated by glucose level to lesser
degrees by a.a, FFA, ceton bodies
 increases gluconeogenesis, lipogenesis, protein
synthesis.
 There is a biphasic insulin response to trauma:
within first hours there is a suppression of insulin
due to chatecholamines, afterwards normal or
increased insulin production follows. But as there
is generally an insulin resistance after trauma,
hyperglycemia continues.
HORMONES CONTROLLED BY
AUTONOMOUS NERVOUS S.
 Glucagon: stimulated by plasma glucose
level
 increases gluconeogenesis and lypolysis
 Following trauma there is a decrease, but
after 24 hours it is increased and stays so
for 3 days.
METABOLIC RESPONSE
 EBB PHASE: Occurs within minutes after trauma:
hypovolemic shock, hypoxia, decrease in energy
expenditure and urinary Nitrogen secretion
 FLOW PHASE: Occurs hours after trauma.Tissue
perfusion is restored, volume deficit is controlled,
there is a hypermatabolic status, hyperglicemia,
hyperthermia,neg N balance, has two sub phases:
catabolic and anabolic sub phases
METABOLIC RESPONSE
Physiological hormones
phase time role changes

24 hours Volume BMR,O2 usage, Catecholamines,

ebb storage temp decrease cortisol,aldosteron
Vasoconstr,CO2,
A.P.Prot increase

flow
catabolic 3-10 days Energy storage BMR,O2 usage, Glucagon, insulin,
temp increase kortisol, catech
Neg N balance increase
ins.resistance
anabolic 10-60 days Replacement of Positive N GH IGF
lost tissue balance
METABOLIC RESPONSE
 Besides loss of muscular tissue and storage of
extracellular fluid there is an increase in need of
energy.
 The most severe traumas are burns, when energy
exp is increased by 100 % even during resting.
 Energy expenditure
resting: 25-30 ccal/kg/day
hospital stay: 36-49 ccal/kg/day
severely injured:50-70 ccal/kg/day
METABOLIC RESPONSE
 1g glucose: 4 ccal
 1g protein: 4 ccal
 1g fat: 9 ccal
 Total calory: ch 50%, lipids 30 %, proteins
10%
 Posttraumatic: within the first hours
glycogen is used
 Lipids become the major source (40%)
METABOLIC RESPONSE
 Carbohydrate metb after trauma: Due to
hepatic glycogen hyperglycemia occurs
and lasts till flow phase.
 Glucose is used by RBC, NS and wounds
which do not need insulin
 Hyperglycemia contributes to the osmotic
pressure to store the intravascular volume
METABOLIC RESPONSE
 Lipid metb after trauma: They are primary
energy sources, increased by ACTH,
cortisol, catecholamines, glucagon, GH
 During ebb phase FFA and glycerol are
increased
 Also during flow phase FFA are high and
used by heart and skleton muscles.
METABOLIC RESPONSE
 Protein metb after trauma: Urinary loss of N
upto 50 g/day
 Mostly due to loss of skeleton muscle
 Maximal during the end of the first week
 Alanin, Cystin and Taurin and aromatic a.a
are increased. GIS cells, fibroblasts and
lymphcyts use as major energy source
glutamine.
ENDOGENOUS RESERVES
CARBOHYDRATES 90-400 gr 360-1600 KCAL

PROTEINS 10-12 KG 40000-48000

KCAL

LIPIDS 17 KG 150 000 KCAL