METABOLIC TRAUMA

(STRESS RESPONSE
TO SURGERY)
Stress response is the term used to describe the
widespread metabolic ,hormonal & inflammatory
changes which occur in response to trauma,
including surgical trauma

Described by Cuthbertson in 1929

 Magnitude of the metabolic
response is proportional to
the severity of surgery

Components

Neuroendocrine Cytokine response/

response Inflammatory response
 Stress response is a complex neuroendocrine
response & the net effect is:

Increase catabolism

Release endogenous fuel stores,

and conserves body fluids
? Evolved to protect the body from injury & to enhance
chances of survival

Physiological changes that occur are

found to be detrimental
CHANGES OCCURING DURING STRESS
HORMONAL CHANGES ASSOCIATED WITH
METABOLIC RESPONSE TO TRAUMA
 NEUROENDOCRINE RESPONSE

Activation of the sympathetic nervous system &

HPA axis

Release of cortisol

Insulin

Growth hormone(GH) & Arginine vasopressin

(ADH)

Other hormonal effects

 INITIATION OF RESPONSE

Activates the
Afferent nerve SNS (modifies
Areas of tissue inputs hepatic,
damage/injury (somatic & pancreatic &
autonomic) renal
functions)

Stimulates adrenal
medullary
catecholamines + Stimulates CVS
release of Hypertension
norepinephrine (NE) Tachycardia
from pre-synaptic
nerve terminals
SNS EFFECTS ON KIDNEY & PANCREAS

Release of renin from kidneys

Converts angiotensin 1 to angiotensin 2

Stimulates the release of Aldosterone from adrenal

cortex

Increase Na+ & H2O reabsorption from the DCT in the

kidneys
 SNS EFFECTS ON KIDNEY & PANCREAS

Release of Glucagon from the pancreas

Stimulates breakdown of glycogen in liver & muscle

Increase glucose & lactate concentration & mobilizes

FFA from lipid stores
 HPA axis

Hypothalamic
releasing
factors
respond to Release
major surgical ACTH
trauma by Stimulates
stimulating adrenal
the anterior glucocorticoid
pituitary & GH release
 HPA axis
GH enhance
protein
Stimulates
synthesis &
lipolysis
inhibits
breakdown
Effects
Produce
increase
Antagonises amounts of
Insulin ADH by the
posterior
pituitary

MARKED INCREASE IN CATABOLIC HORMONES & SUPPRESSION OF

ANABOLIC HORMONES
 CORTISOL

 Released from the adrenal cortex after stimulated by

ACTH

 Normal baseline value= 400nmol/L

 Can increase up to 1500nmol/L within 4-6 hours of

major surgery

 Normal feedback mechanism of control of hormone

secretion is lost
 EFFECTS OF CORTISOL RELEASE
 Skeletal muscle protein breakdown to provide gluconeogenic
precursors

 Provide amino acids for protein synthesis in the liver

 Stimulates lipolysis

 Impaired glucose utilization (“anti-insulin effect”)

hyperglycaemia

 Anti-inflammatory effects (mediated by a reduced production of

inflammatory mediators- cytokines/PG/Leukotrines)

 Mineralocorticoid effects: salt & water retention & potassium

loss
 INSULIN

Major anabolic
hormone which
promotes glucose
utilization & glycogen
synthesis

Body fails to secrete

insulin in response to
It’s effects are unable trauma; caused by
to match the catabolic inhibition of beta cells
response in the pancreas by
alpha 2 adrenergic
inhibitory effects of
catecholamines
Later Insulin resistance develops due to a
defect in the insulin receptor or a defect in the
intracellular signalling pathway

In the perioperative setting

State of functional Insulin deficiency

(In contrast to Insulin, Glucagon promotes hepatic

glcogenolysis & gluconeogenesis, but Insulin effects
predominate)
 GROWTH HORMONE
 Has mixed catabolic & anabolic effects

 Increase secretion after surgery has only minor

physiological role

Effects:
• Promotes glycogenolysis
• Promotes lipolysis
• Inhibits the uptake & utilization of glucose by cells
• Release of IGF (insulin like growth factor)-
Somatomedin C; reduces protein catabolism &
promote tissue repair
 AVP

Has an anti-diuretic effect

Important vasopressor &

enhances haemostasis

Enhance release of ACTH

BETA ENDORPHINS & PROLACTIN

Physiological effects of increase

secretion of both hormones during
surgery are unknown

May alter immune function

 THYROID HORMONES

 T3 is 5 times more active than T4

 Bound to albumin, thyroxine binding pre-albumin

& thyroid binding globulin

 Thyroid hormones stimulate O2 consumption in

many organs Increase metabolic rate &
increase heat production

*After surgery there is a reduction in hormone

production, which returns to normal over a few
days
Different levels of the metabolic response to stress
J C Preiser et al Br J Anaesthesia 2014
 SUBSTRATE MOBILIZATION

Overall metabolic effect of endocrine

response is the mobilization of
substrate from carbohydrate (CHO),
lipid and protein stores
 CHO Metabolism
Catecholamines & Cortisol Glycogenolysis +
Gluconeogenesis Hyperglycaemia

Initial failure of Insulin secretion + Insulin resistance

Magnitude of the hyperglycaemic response reflects

the severity of surgery

Glucose concentration >12 mmol/L:

• Impairs wound healing
• Increases infection rates
• Increase risk of ischaemic damage to the
nervous system & myocardium
 PROTEIN METABOLISM

Initially during the stress response protein

anabolism is inhibited

Later (severe stress response) Enhanced

catabolism

Increase cortisol & cytokine concentration,

stimulates protein catabolism

After major abdominal surgery 0.5kg/day of

lean body mass may be lost (significant muscle
wasting & weight loss)
 PROTEIN METABOLISM

Catabolism mainly affects the skeletal muscle

proteins Release of amino acids (AA)

AA released from new proteins in the liver

Acute Phase Proteins

AA are used for gluconeogenesis

Reduced albumin production, interferes with the

maintenance of the extracellular volume
 LIPID METABOLISM
Increase catecholamines/ cortisol /glucagon + Insulin
deficiency Promotes lipolysis & Ketone body
production

Triglycerides are metabolized to FA & Glycerol

(gluconeogenic substrates)

High glucagon + low Insulin Promotes

oxidation of FFA to acyl COA converted in the
liver Ketone bodies (useful water soluble fuel
sources)
 SALT & WATER METABOLISM

Salt & water retention

Release
of AVP Forms concentrated urine

Potassium loss (may continue

to 3-5 days after surgery)

Secretion of Renin from JG cells of the kidneys

Promotes Na+ & H2O retention from DCT

 CYTOKINES

 Low molecular weight heterogenous glycoproteins

 Include IL 1-17, Interferons, TNF

 Tissue injury from trauma/ surgery Activates

macrophages/ fibroblasts/endothelial & glial cells
synthesize cytokines

Most of the effects are exerted locally (paracrine), but

can act systemically (endocrine)
 
Cytokines mediate immunity & inflammation
 Effects of Cytokines:
Acute phase response (fever,
granulocytosis, haemostasis, limits tissue
damage, promotes healing)
 Immune system and neuroendocrine
system are closely related

Cytokines may increase the release of

cortisol (in vitro)

AND

Cytokine production is limited by cortisol in

a negative feedback system
WHAT ARE THE OTHER TRIGGERS OF THE
NEUROENDOCRINE & CYTOKINE
RESPONSE?

 Pain & anxiety

 Starvation
 Hypothermia & shivering
 Haemorrhage
 Acidosis
 Hypoxia
 Infection
 SYSTEMIC EFFECTS OF THE STRESS
RESPONSE

CARDIOVASCULAR:
• Increase myocardial O2 demand by increasing heart
rate & BP
• Coronary artery vasoconstriction
• Increase ADH Increase platelet adhesiveness
• Vascular endothelium: Produces NO, which causes
vasodilatation
 SYSTEMIC EFFECTS OF THE STRESS
RESPONSE
RESPIRATORY:
Reduced FRC V/Q mismatch
 
GASTROINTESTINAL:
Paralytic ileus (delays resumption of enteral feeds)
 
IMMUNOLOGICAL:
Cortisol/ Interleukins/Prostaglandins
Immunosuppression
 SHOULD WE MODIFY THE METABOLIC
RESPONSE?

Yes!

HOW?

By combining recent developments in surgical &

anaesthetic practice
 Surgical technique: Minimally invasive surgery
 Anaesthesia: - Drugs

Opioids- suppress hypothalamic and pituitary hormone

secretion (large dose fentanyl)
 SHOULD WE MODIFY THE METABOLIC
RESPONSE?

Etomidate/ Benzodizepines/Clonidine

 Regional anaesthesia- spinal/epidural (reduce

hormonal effects but cytokine response
remains unaltered)

 Nutrition: prevents adverse effects of the

stress response (enteral- immune-nutrition)

 Maintain normothermia/ Hormone therapy?

QUESTION? March 2008- structured essay
paper

1. Define homeostasis

2. What are the components of a

negative feedback loop

3. Describe the endocrine

response to stress

4. Outline the metabolic response

to surgical trauma
 ANSWER
Homeostasis:
Property of an organism or system that helps maintain its parameters
within normal range of values (internal conditions remain stable &
relatively constant)

Components:
Factor Sensor Integrating Centre Effector

Endocrine response: HPA axis and the effects of hormones

Metabolic response: CHO/Protein/Lipid metabolism

 CONCLUSION

Neuroendocrine, metabolic & inflammatory aspects of

injury are a part of the overall stress response

Stress response results in;

 SNS activation associated with immunological &
haematological changes
 Substrate mobilization
 Sodium and water retention
 Suppression of anabolic hormone secretion
 Muscle protein loss

Benefits of stress response in modern medicine are

not obvious
Physiological effects cause detrimental effects
THANK YOU !