The body responds to stress and injury through metabolic and inflammatory responses known as the ebb and flow phases. In the initial ebb phase, metabolism decreases to conserve energy and resources. The subsequent flow phase involves increased metabolism and inflammation to restore function and fight infection. Prolonged or excessive response can lead to organ dysfunction or failure through effects like fluid shifts, immune imbalance, and metabolic changes that impact protein, carbohydrate and fat metabolism. Factors like severity of injury, infection, fluid status, and nutrition influence the response and clinical outcomes.

2. ILOs
• At the end of this presentation students will be able to
describe:
 Body’s local and systemic response to injury.
 Interventions to minimize harmful effects.
 Clinical spectrum of SIRS

3. Metabolic response to stress (tissue injury, infection) is divided into the ebb and
flow phase Energy expenditure
• Ebb Phase
• Flow Phase
• Restore tissue function
• Eradicate invading Microorganisms—Bacterial Translocation

4.  Once the systemic response is activated, the physiologic and metabolic changes
that follow are similar and may lead to septic shock
 Ebb phase: initial response to bodily insult, occur immediately following injury
(short term)
Flow phase: neuroendocrine response to physiologic stress following the ebb
phase (long term)

5.  In the ebb phase, the body shuts down‘ and the metabolic rate decreases
Leads to hypovolemic shock:
↓ Blood pressure
↓ Cardiac output
↓Body temperature
↓tissue perfusion
↓O2 consumption
↓ metabolic rate
 Insulin levels drop because glucagon is elevated.

6. SYSTEMIC CONSEQUENCES OF RESPONSES TO INJURY
Hypovolaemia (moderate to severe injury) due to:
- Loss of blood, electrolyte containing fluid/ water.
- Loss of protein rich fluid in 3rd space (24-48 hrs).
Greater loss in burn, ischemia and infection
- Result: reduced O₂ & nutrient delivery to tissues

7. IMMUNOLOGICAL RESPONSE
• Proinflammatory: Activation of cellular processes designed
to restore tissue function and eradicate invading
microorganisms.
• Anti-inflammatory: Preventing excessive proinflammatory
activities & restoring homeostasis in the individual.

8.  Cytokines Interleukin-1, interleukin-6, and tumor necrosis factor
(TNF)
 Released by phagocytes in response to tissue damage, infection,
inflammation, and some drugs and chemicals

10. Acute Inflammatory Response
• Tissue damage→ Activation of tissue MACROPHAGE → CYTOKINES release - IL1, IL6, IL8,
TNFα
• IL8 - attracts circulating MACROPHAGE & NEUTROPHILS
• IL1,IL6, TNFα activates inflammatory cells to kill bacteria
• C-reactive protein used as a biomarker

11. Acute Inflammatory Response- contd.
• Other substances released:
• PRO-INFLAMMATORY: Prostaglandins, complement, free radicals
• ANTI-INFLAMMATORY: IL10, antioxidants (VIT. A,C)
• IL-10 Inhibits immune function
• -Balance between PRO AND ANT-INFLAMMATORY process

12. ENDOTHELIUM & BLOOD VESSELS RESPONSE
• Leucocyte- adhesion to endothelium & transmigration
• Vasodilatation – due to kinins, prostaglandins, nitric oxide release
• Increased capillary permeability delivering inflammatory cells, O₂, nutrients- all important
for healing
• Colloid leak (mainly albumin) → oedema

13. • Coagulation & reduced bleeding: due to tissue factors & activated platelets.
• If inflammatory process generalized → microcirculatory thrombosis
& disseminated intravascular coagulation (DIC)

14. ROLE OF AFFRENT NERVE IMPULSES
• Injury & inflammation: stimulates afferent pain fibres → via
spinothalamic tract stimulus reaches to thalamus which stimulates:
↓
• Sympathetic NS: Noradrenaline (sympathetic nerve ends) &
Adrenaline from adrenal medulla → tachycardia, increased cardiac
output, changes in carbohydrate, protein & fat metabolism

15. • Hormone release:
- Increased secretion of stress hormones
- Decreased secretion of anabolic hormones

16. • Characteristics of flow phase
Increase tissue oedema
Increase BMR (basal metabolic rate)
Increase CO
Increase temperature
Increase WBC
Increase Oxygen consumption
Increase gluconeogenesis

17. Once the blood pressure is stabilized, the flow (recovery) phase
begins
Divided into 2 response:
Acute Response: catabolism predominates
 Adaptive Response: anabolism predominates

18.  Acute Response:
 Catabolism predominates: Initial, lasts up to 1 week
 glucocorticoids
 glucagon
 catecholamines
 Release cytokines,
 lipid mediators
 Acute phase protein (CRP)
 N2 excretion
 metabolic rate
 O2 consumptions

19. Adaptive Response: 2-4 weeks
Anabolism predominates
 Hormonal response gradually diminished
↓ hypermetabolic rate
 Assoc with recovery
 Restore body protein
 Wound healing

21.  Metabolic changes in the stressed (critically ill patient):
Energy metabolism
Protein metabolism
Carbohydrate metabolism
Fat metabolism
Others

22. ACTH—acts on adrenal cortex to release cortisol (mobilizes amino
acids from skeletal muscles)
 Catecholamines—epinephrine and norepinephrine from renal
medulla to stimulate hepatic glycogenolysis, fat mobilization,
gluconeogenesis

23. Aldosterone—causes renal sodium retention
Antidiuretic hormone (ADH)—stimulates renal tubular water
absorption
These conserve water and salt to support circulating blood volume

24. Fluid conserving measures
• Sodium & water retention (Oliguria):
-↑ADH (injury, atrial stretch receptors, osmoreceptors, pain, anxiety)- free water retention
-↑Aldosterone (stimulated by renin-angiotensin, ACTH, ADH)-
increase reabsorption of water & Na⁺ (↓ Na in urine)
- ADH & Aldosterone remain elevated for 48-72 Hours
• Increased sympathetic activity- compensatory increase in
CO & peripheral vasoconstriction (↑BP)- ensures adequate tissue perfusion.

26.  No extra sodium is needed in the first 24 – 48

27. HORMONAL CHANGES
PITUITARY ADRENAL PANCREAS OTHERS
INCREASED
SECRETION
GH
ACTH
PROLACTIN
ADH
ADRENALINE
CORTISOL
ALDOSTERONE
GLUCAGON RENIN
ANGIOTENSIN
UNCHANGED
TSH
LH
FSH
- - -
DECREASED
SECRETION - - INSULIN
TESTOSTERONE
OESTROGEN
THYROID
HORMONES

28. INCREASED METABOLISM
• Energy expenditure rise (10-30%) due to:
• Increased thermogenesis due to inflammatory response (IL1)
• Increased BMR-↑ metabolism of carb., protein, fat. (increased ion pump & cardiac activity)
Patients following major surgery/ severe trauma are in a state of:
• Catabolism: increased breakdown of nutrients to its constituents ( glucose, amino acid & fatty acids)
• Starvation : ( low intake & increased demand)

29. CARBOHYDRATE METABOLISM
• ↑Catecholamines & Glucagon:
• Stimulates glycogenolysis in the liver.
• Gluconeogenesis (lactate, amino acids, glycerol) in the liver.
• Insulin- secretion suppressed
• Net result: Hyperglycaemia and impaired cellular glucose uptake
• Glucose available for - repair and inflammatory process
• Severe hyperglycaemia- Increases morbidity & mortality.
Should be controlled in perioperative period.

30. FAT METABOLISM
• Catecholamines, Glucagon, cortisol & growth hormone:
• Activate triglyceride lipase in adipose tissue.
• Lipolysis- glycerol & free fatty acids (FFA).
• Glycerol used in gluconeogenesis.
• FFA converted to ketone in liver & to ATP in most tissues.
• Brain uses ketone for energy when less glucose available.

31. PROTEIN METABOLISM
• Proteolysis (skeletal muscle) mediated primarily by glucocorticoids
• ↑urinary nitrogen excretion to ˃30 g/d (normal 10-20 g/d).
• Amino acids (AA): Used for gluconeogenesis and other activity
• Not a long-term fuel reserve.
• Excessive protein depletion-(25-30% lean body wt.)incompatible with life.
• Catabolism: Correspond to- severity & duration of injury.
• Feeding can’t reverse catabolism but reduces it.

32. PROTEIN METABOLISM (AMINO ACIDS FROM PROTEOLYSIS)
• 1. Glucogenic AA (alanine, glycine, cysteine)- gluconeogenesis in liver
• 2. Other AA (Krebs cycle) pyruvate, acetyl co. A - gluconeogenesis
• 3. Substrate for acute phase proteins (liver)- C reactive protein
• Role of acute phase protein not known ? defence or healing

33. CHANGES IN RBC AND COAGULATION
• Anaemia: Blood loss, haemodilution, impaired RBC production in bone
marrow (↓ erythropoietin)
• Hypercoagulable state: (Endothelial injury, platelet activation, venous stasis,
increased procoagulant factors) Increased risk of thrombo-embolism

35. CLINICAL SPECTRUM OF INFECTION &
SYSTEMIC INFLAMATORY RESPONSE SYNDROME (SIRS)
• Terminologies to describe various facets of inflammation:
• SIRS: 2 or more of following:
 Temperature ≥38°C or ≤36°C
 Heart rate ≥90 beats/min
 Respiratory rate ≥20/mi
 WBC count ≥12,000/L or ≤4000/L
• Sepsis: Identifiable source of infection + SIRS
• Severe sepsis: Sepsis + organ dysfunction
• Septic shock: Sepsis + cardiovascular collapse

36. Diagnosis of Systemic Inflammatory Response Syndrome (SIRS)
•Site of infection established and at least two of the following are present
•Body temperature at38 C or lt36 C
•Heart rate at 90 beats/minute
•Respiratory rate at20 breaths/min (tachypnea)
•PaCO2 lt32 mm Hg (hyperventilation)
•WBC count gt12,000/mm3 or lt4000/mm3
•Bandemia presence of 10 bands (immature neutrophils) in the absence of chemotherapy-induced neutropenia
and leukopenia
•
•May be caused by bacterial translocation

37. Multiple organ dysfunction Syndrome MODS:
Results when major physiological insult could lead to failure of one or
more organ remote from the initiating disease
Pulmonary failure occuring first as ( ARDS ) , followed by hepatic ,
intestinal , renal and finally cardiac.
The mortality of MODS is directly related to number of organ that fail.

38. ANABOLISM
• Pro-inflammatory cytokine has subsided
• Regaining weight, skeletal muscle mass, and fat, lasts for 3-13 weeks or longer.
• Patients feel better, regain appetite
• Hormones involved: Insulin, insulin like growth factor, growth hormone, androgens, 17-
ketosteroids
• Adequate nutrition & early mobilization promote enhanced recovery.
• Late anabolic phase positive caloric balance, gain in weight and body fats. lasts for months
to years.

39. FCTORS MODIFYING RESPONSE TO INJURY
• Patient related factors: Coexisting illness, medications, nutritional status, genetic
factors.
• Injury related factors: Severity, nature (burn, ischemia), temperature.
• Response magnitude can be minimized by: minimal invasive surgery , minimizing
blood loss, preventing/ treating infection, use of loco-regional anaesthesia.

40.  How to decrease the response to injury:
Pain relief
Adequate fluid replacement
Treatment of the infection
Careful surgical technique
Minimal surgical procedures
Type of the anaethesia
Maintenance of normothermia
Nutritional support

41.  Glutamine and other amino acids have important roles in liver and renal failure.
 Growth hormone usefulness in enabling patients to become anabolic earlier
 Immune-enhancing formulas
• improve immune function, modulate cytokine production,
• decrease wound infections
• improve patient recovery from major surgery.
Metabolic response modification

42.  Epidural anaesthesia
• blocks much of the early stress response to surgery
• slowing protein loss.
•
• immediate post-operative period mobility
• limit post-operative ileus.
 NSAID preventing arachidonic acid mediated tissue damage
 Antioxidants in limiting free oxygen radical damage.
 Minimally invasive surgical interventions led to early recovery from surgery and faster return
to work.
Metabolic response modification

43. IN SUMMARY

44. Mediators of Injury Response :
Neuro – Endocrine [ Hormonal ]
Immune System [ Cytokines ]

45. Response Components
Physiological Consequences
Metabolic Manifestations
Clinical Manifestations
Laboratory

46. PHYSIOLOGICAL
↑ Cardiac Output
↑ Ventilation
↑ Membrane Transport
Weight loss
Wound Healing

47. METABOLIC Response Components
Hypermetabolism
Accelerated Gluconeogenesis
Enhanced Protein breakdown
Increased Fat oxidation

48. CLINICAL Components
Fever
Tachycardia
Tachypnoea
Presence of wound or Inflammation
Anorexia

49. LABORATORY Response
Leucocytosis/Leucopenia
Hyperglycemia
Elevated CRP/Altered acute phase reactants
Hepatic/Renal dysfunction

51. THANKS