A presentation on Metabolic Responses to Injury

1. METABOLIC RESPONSES TO
INJURY
PRESENTED BY-
DR. UMME HABIBA DILSHAD MUNMUN
RESIDENT (PHASE-A)
PAEDITRIC SURGERY

2. OBJECTIVES
 HOMEOSTASIS - CONCEPT
 COMPONENTS OF RESPONSES
 MEDIATORS OF RESPONSES
 PHASES OF RESPONSES & KEY ELEMENTS
 FACTORS – EXACERBATE & AVOIDABLE

3. HOMEOSTASIS

4. HOMEOSTASIS
‘THE STABILITY OF THE “MILIEU INTÉRIEUR” IS THE PRIMARY CONDITION FOR FREEDOM
AND INDEPENDENCE OF EXISTENCE’
(CLAUDE BERNERD- 1843)
THAT IS,
BODY SYSTEM ACT TO MAINTAIN INTERNAL CONSTANCY

5. HOMEOSTASIS
‘THE CO-ORDINATED PHYSIOLOGICAL PROCESS WHICH MAINTAINS MOST OF THE STEADY
STATES OF THE ORGANISM’
(WALTER CANON- 1933)
THAT IS,
ESSENTIALLY ALL ORGANS AND TISSUES OF THE BODY PERFORM
FUNCTIONS THAT HELP MAINTAIN THESE CONSTANT CONDITIONS

6. HOMEOSTASIS

7. HOMEOSTASIS
BASIC CONCEPT IS-
 STRESS-FREE PERI-OPERATIVE CARE HELPS TO PRESERVE HOMEOSTASIS
FOLLOWING ELECTIVE SURGERY
 RESUSCITATION, SURGICAL INTERVENTION & CRITICAL CARE CAN RETURN
THE SEVERELY INJURED PATIENT TO A SITUATION IN WHICH HOMEOSTASIS
BECOMES POSSIBLE ONCE AGAIN.

8. NATURE OF THE INJURY RESPONSE
METABOLIC RESPONSE TO INJURY IS GRADED: THE MORE SEVERE THE INJURY THE
GREATER THE RESPONSE.

9. NATURE OF THE INJURY RESPONSE
THIS CONCEPT NOT ONLY APPLIES TO PHYSIOLOGICAL/METABOLIC CHANGES BUT ALSO TO
IMMUNOLOGICAL CHANGES /SEQUEL.
IMMUNOLOGICAL
CELLULAR
RESPONSE
HORMONAL

10. RESPONSE COMPONENTS
 PHYSIOLOGICAL CONSEQUENCES
 METABOLIC MANIFESTATIONS
 CLINICAL MANIFESTATIONS
 BIOCHEMICAL CHANGES

11. RESPONSE COMPONENTS
PHYSIOLOGICAL
 ↑ CARDIAC OUTPUT
 ↑ VENTILATION
 ↑ MEMBRANE TRANSPORT
 WEIGHT LOSS
 WOUND HEALING
METABOLIC
 HYPER METABOLISM
 ACCELERATED GLUCONEOGENESIS
 ENHANCED PROTEIN BREAKDOWN
 INCREASED FAT OXIDATION

12. RESPONSE COMPONENTS
CLINICAL
 FEVER
 TACHYCARDIA
 TACHYPNOEA
 PRESENCE OF WOUND OR
INFLAMMATION
 ANOREXIA
BIOCHEMICAL
 LEUCOCYTOSIS / LEUCOP ENIA
 HYPERGLYCEMIA
 ELEVATED CRP/ALTERED ACUTE
PHASE REACTANTS
 HEPATIC / RENAL DYSFUNCTION

13. MEDIATORS OF INJURY RESPONSE
 NEURO – ENDOCRINE [HORMONAL]
 IMMUNE SYSTEM [CYTOKINES]

14. NEURO-ENDOCRINE (HORMONAL)
RESPONSE
BIPHASIC :
 ACUTE PHASE - AN ACTIVELY SECRETING PITUITARY & ELEVATED COUNTER
REGULATORY HORMONES (CORTISOL, GLUCAGON, ADRENALINE).
 CHRONIC PHASE - HYPOTHALAMIC SUPPRESSION & LOW SERUM LEVELS
OF THE RESPECTIVE TARGET ORGAN HORMONES.

17. PURPOSE - NEURO-ENDOCRINE RESPONSE
 PROVIDE ESSENTIAL SUBSTRATES FOR SURVIVAL
 POSTPONE ANABOLISM
 OPTIMISE HOST DEFENCE

18. IMMUNOLOGICAL (CYTOKINE) RESPONSE
PROINFLAMMATORY PHASE COUNTER REGULATORY PHASE
 IL-1, IL-6, TNF-ALPHA
 HYPOTHALAMUS → PYREXIA
 HEPATIC ACUTE PHASE PROTEIN
 IL-1 RECEPTOR ANTAGONIST (IL-
1RA) AND TNFSOLUBLE RECEPTORS
(TNF-SR-55 AND 75)
 PREVENT EXCESSIVE
PROINFLAMMATORY ACTIVITIES
 RESTORE HOMEOSTASIS

19. METABOLIC RESPONSE
INJURY
EBB FLOW
HOURS DAYS
RECOVERY
WEEKS
SHOCK CATABOLISM ANABOLISM
BREAKING DOWN
ENERGY STORES
BUILDING UP USED
ENERGY

20. EBB PHASE
EBB PHASE
DURATION
24 – 48 HRS
ROLE
CONSERVE – BLOOD,
VOLUME & ENERGY
RESERVES - REPAIR
PHYSIOLOGICAL
↓ BMR, ↓ TEMP, ↓ CO,
HYPOVOLAEMIA, LACTIC
ACIDOSIS
HORMONES
CATECHOLAMINES, CORTISOL,
ALDOSTERONE

21. FLOW PHASE
FLOW PHASE
DURATION
3 – 10 DAYS
ROLE
MOBILISATION OF ENERGY
STORES – RECOVERY &
REPAIR
PHYSIOLOGICAL
↑ BMR, ↑ TEMP, ↑ O2
CONSUMPTION, ↑ CO
HORMONES
CYTOKINES + ↑ INSULIN,
GLUCAGON, CORTISOL,
CATECHOL BUT INSULIN
RESISTANCE
ANABOLIC
DURATION
10 – 60 DAYS
ROLE
REPLACEMENT OF LOST
TISSUE
PHYSIOLOGICAL
+VE NITROGEN BALANCE
HORMONES
GROWTH HORMONE,
IGF
CATABOLIC

22. KEY CATABOLIC ELEMENTS OF FLOW PHASE
 HYPERMETABOLISM
 ALTERATIONS IN SKELETAL MUSCLE PROTEIN
 ALTERATIONS IN HEPATIC PROTEIN
 INSULIN RESISTANCE

23. HYPERMETABOLISM
 MAJORITY OF TRAUMA PATIENTS - ENERGY EXPENDITURE APPR. 15-25%
> PREDICTED HEALTHY RESTING VALUES.
 FACTORS WHICH INCREASES THIS METABOLISM :
 CENTRAL THERMODYSREGULATION (CAUSED BY PROINFLAMMATORY CYTOKINE
CASKET)
 INCREASED SYMPATHETIC ACTIVITY
 INCREASED PROTEIN TURNOVER
 WOUND CIRCULATION ABNORMALITIES

24. SKELETAL MUSCLE – METABOLISM
 MUSCLE WASTING – RESULT OF ↑ MUSCLE PROTEIN DEGRADATION + ↓
MUSCLE PROTEIN SYNTHESIS. (RS & GIT). CARDIAC MUSCLE IS SPARED.
 IS MEDIATED AT A MOLECULAR LEVEL MAINLY BY ACTIVATION OF THE
UBIQUITIN-PROTEASE PATHWAY.
 LEAD - INCREASED FATIGUE, REDUCED FUNCTIONAL ABILITY, ↓QOL & ↑
RISK OF MORBIDITY & MORTALITY.

25. HEPATIC ACUTE PHASE RESPONSE
 CYTOKINES – IL- 6 ↑ SYNTHESIS OF POSITIVE
ACUTE PHASE PROTEINS : FIBRINOGEN & CRP
 NEGATIVE ACUTE REACTANTS : ALBUMIN DECREASES

26. HEPATIC ACUTE PHASE RESPONSE

27. INSULIN RESISTANCE
 POST OPERATIVE HYPERGLYCAEMIA – ↑ GLUCOSE PRODUCTION + ↓
GLUCOSE UPTAKE IN PERIPHERAL TISSUES.
 DUE TO CYTOKINES & DECREASED RESPONSIVENESS OF INSULIN-
REGULATED GLUCOSE TRANSPORTER PROTEINS.
 THE DEGREE OF INSULIN RESISTANCE IS ∞ TO MAGNITUDE OF THE
INJURIOUS PROCESS.

28. CHANGES IN BODY COMPOSITION – FOLLOWING
SURGERY
 CATABOLISM – DECREASE IN FAT MASS & SKELETAL MUSCLE
MASS.
 BODY WEIGHT – PARADOXICALLY INCREASE BECAUSE OF
EXPANSION OF EXTRACELLULAR FLUID SPACE.

29. FACTORS EXACERBATE THE RESPONSE TO INJURY
 HYPOTHERMIA
 PAIN
 STARVATION
 IMMOBILIZATION
 SEPSIS
 HYPOTENSION

30. FACTORS EXACERBATE THE RESPONSE TO INJURY

31. AVOIDABLE FACTORS THAT COMPOUND THE RESPONSE
TO INJURY
 CONTINUING HAEMORRHAGE
 HYPOTHERMIA
 TISSUE OEDEMA
 TISSUE UNDERPERFUSION
 STARVATION
 IMMOBILITY

32. AVOIDABLE FACTORS
VOLUME LOSS :
LIMIT INTRA OPERATIVE ADMINISTRATION OF
BALANCED CRYSTALLOIDS CAREFULLY
NO NET WEIGHT GAIN
REDUCE POST OPERATIVE COMPLICATIONS
LENGTH OF STAY

33. AVOIDABLE FACTORS
ADMINISTRATION OF ACTIVATED PROTEIN C - TO CRITICALLY ILL PATIENTS
↓ ORGAN FAILURE AND DEATH.
VIA PRESERVATION OF THE MICRO CIRCULATION IN VITAL ORGANS.

34. AVOIDABLE FACTORS
 MAINTAINING THE NORMOGLYCEMIA WITH INSULIN
INFUSION DURING CRITICAL ILLNESS
 PROTECT THE ENDOTHELIUM
 CONTRIBUTE TO THE PREVENTION OF ORGAN FAILURE
AND DEATH.

35. AVOIDABLE FACTORS
 STARVATION : DURING STARVATION, THE BODY IS FACED WITH AN
OBLIGATE NEED TO GENERATE GLUCOSE TO SUSTAIN CEREBRAL ENERGY
METABOLISM(100G OF GLUCOSE PER DAY).
 PROVISION OF AT LEAST 2L OF IV 5% DEXTROSE FOR FASTING
PATIENTS PROVIDES GLUCOSE AS ABOVE.

36. AVOIDABLE FACTORS
 TISSUE OEDEMA : IS MEDIATED BY THE VARIETY OF MEDIATORS
INVOLVED IN THE SYSTEMIC INFLAMMATION. CAREFUL ADMINISTRATION
OF ANTI-MEDIATORS & REDUCE FLUID OVERLOAD DURING
RESUSCITATION REDUCES THIS CONDITION.
 IMMOBILITY : POTENT STIMULUS FOR INDUCING MUSCLE WASTING.
 EARLY MOBILIZATION IS AN ESSENTIAL MEASURE TO AVOID MUSCLE
WASTING.

37. CONCEPTS BEHIND ENHANCED
RECOVERY AFTER SURGERY (ERAS)

38. ENHANCED
RECOVERY AFTER SURGERY (ERAS)

39. PROTECTIVE APPROACH TO PREVENT UNNECESSARY
ASPECTS OF STRESS RESPONSE
 MINIMAL ACCESS TECHNIQUES
 MINIMAL PERIODS OF STARVATION
 EPIDURAL ANALGESIA
 EARLY MOBILIZATION

40. TAKE HOME MESSAGE
 WE SHOULD RESPECT THE TISSUE BY DOING LESS TRAUMA BY
CAREFUL HANDLING MIMICS INVASIVE SURGERY
 SHOULD HAVE THE POTENTIAL TO REDUCE THE STIMULI, INCLUDING
TRAUMA/INJURY, IN ORDER TO ALLEVIATE THE EFFECT OF SURGERY