Metabolic Response to Stress and Energy Requirements

Dr B Ravinder Reddy
MBBS, MS, FRCS (Edinburgh), FRCS (Glasgow)
Chief of Division of Clinical Nutrition
Consultant General & Gastrointestinal Surgeon
Care Hospital –The Institute of Medical Sciences
Banjara Hills, Hyderabad (AP) India
Email: bravinderreddy@doctor.com

Contents:
• Mechanism of stress response
• Metabolic effects due to fasting during stress
• Metabolism of energy during stress
• Energy requirements during stress

Physiologic response to stress:

This is an overview of the mechanisms of physiologic response to stress and the
effect of critical illness on starvation and energy metabolism. It simplifies the
rules for energy supply in the critically ill patients.

1. Mechanism of response to stress: Critical illness causes significant changes

in almost all the organ-systems of the body. Most affected are cardiovascular,
respiratory, endocrine, metabolic and immune systems. Local inflammation
of the tissues initiates the response which is directly proportional to the extent
of initial injury, infection or insult.
Central nervous system initiates the metabolic response to stress. It plays a
key role in adjusting the body to different types of stresses, like critical illness,
trauma, surgery, etc.
The initial tissue injury sets in acute inflammation. This activates endothelial
cells and macrophages. These in turn, activate a cascade of various mediators
to provide adequate adaptation to the inflammatory stress. They include the
pro-inflammatory mediators (IL-1, IL-6, TNF-alpha), anti-inflammatory (IL-4,
IL-10) mediators, coagulation factors, kinins and certain other endogenous
substances. These activate sympathetic-adrenal system, hypothalamic-
pituitary axis and other endocrine organs. Activation of sympathetic system
leads to parallel stimulation of corticotropic axis and vice-versa. As a result of
which, stress hormones like epinephrine, nor-epinephrine, cortisol,
vasopressin, growth hormone and glucagon are released. The thyroid axis is
down regulated and affects the energy metabolism.
This neuro-endocrine response commences rapidly and is sustained over
prolonged periods. It has a dynamic effect on all the systems of the body and

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 plays a critical role in maintaining circulation and perfusion to all the vital
organs and maintains the energy metabolism.

2. Changes due to fasting in critically ill patients: In healthy persons, fasting

induces various changes which adapt the individual to enhance survival.
Adaptations include decreasing the resting metabolic rate and reducing the
muscle breakdown by increasing the production and utilisation of ketone
bodies.
In the critically ill patient, such adaptations are absent. Muscle breakdown and
protein catabolism are elevated throughout the course of critical illness. Stress
hormones and cytokines suppress production and utilisation of ketone bodies.
Hence in the critically ill patient the period of starvation should be limited.
Adequate energy should be supplied as soon as possible.

3. Energy metabolism in stress: The extensive stress response causes an increase

in major metabolic pathways. This results in an increased release of endogenous
substrates and an increased exchange of substrates between organs. Insulin
resistance develops in critically ill, by mechanisms which are still not clear.
However, this causes increase in blood glucose and an increase in
gluconeogenesis. Lipolysis is activated, which results in release of fatty acids.
In healthy individuals, the fat-free mass is about 75%, out of which the vital
organs account for 5% of the body weight. It is the FFM that determines the
resting energy expenditure (REE), which amounts to 20 kcal/kg/d (about 1400
kcal in a 70 kgs adult). Out of this, the vital organs account for only 5% of the
weight, but consume 60% of the REE!
In critical illness, after the initial ebb phase, the duration of flow phase depends
on the degree of critical illness. It depends on extent of increase in stress
hormones, pro-inflammatory cytokines and other endogenous mediators.

Therefore, REE can increases significantly. In severe trauma or sepsis it increases

up to 120% to 150% of the basal values, and up to 140% to 170% in major burns
and multiple organ failure. Additional factors can also influence REE. They
include body temperature, organ failure, pain and certain medications. Presence
of fever increases the REE by 10-15% per degree raise in centigrade. Excessive
pain, respiratory failure, acute liver failure and catecholamines will increase
metabolism.
Hypothermia, sedation, opiates, muscle relaxants (during mechanical
ventilation), beta-blockers will decrease the metabolic rate and REE.

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4. Energy requirements in critical illness: Exact calculation of energy
requirements in the critically ill patients requires sophisticated techniques, like
direct or indirect calorimetry, isotope and fick methods, to name a few. They are
not practical and are not part of the standard clinical care.
There are also several equations like Harris-Benedict, Ireton-Jones, Fusco and
Frankenfield to name a few. These are complex calculations and tend to under
estimate the REE. After correction for factors like stress, they have been found to
be inappropriate as they tend to over estimate the energy requirements.

In routine clinical practice, simple, uncomplicated rules are used to estimate REE:

Low to moderate stress: 20 -25 kcal/kg/per day

Severe sepsis, brain injury, multiple injuries: 25 -30 kcal/kg/per day

Major stress like multiple organ failure, extensive burns: 35 – 40
kcal/kg/per day
In prolonged illness, weekly assessment should be carried out.

Difficulties in calculating energy requirements in the critically ill patients:

Correct determinations of energy needs are possible by using bedside
indirect calorimetry. An accurate determination of the 24 hours
metabolic rate requires 24 hours of measurement, which is not
practical, given the critical nature of illness! The measurement is
usually made over a short period of about 20 to 30 minutes and the 24
hours energy expenditure is extrapolated. This can be erroneous up to
20-30%

There is a high degree of variability between the patients and also
within the same patient as the energy expended is difficult to predict.

The route of feeding may alter the energy requirements to a certain
extent.

Key Messages:
1. Critical illness induces extensive physiological changes
2. Adaptations to fasting is absent
3. REE is increased
4. Exact energy needs are difficult to determine. Indirect
calorimetry is more precise method to calculate needs, but is
cumbersome and not practical.
5. Simple rules are used in routine clinical practice
6. Nutritional support should be started as soon as possible