Systemic response to injury/stress

• Outline
-Introduction
-Response components
-Response manifestations
-Modifying post-traumatic responses
 Introduction
• Definition: systemic inflammatory response
syndrome (SIRS) :sequence of host phenotypic
and metabolic responses to systemic
inflammation.
 changes in heart rate, respiratory rate,
blood pressure, temperature regulation, and
immune cell activation
Term Definition

Identifiable source of microbial insult

Infection Two or more of following criteria are met
SIRS

Temperature 38°C (100.4°F) or 36°C (96.8°F)

Heart rate 90 beats per minute

Respiratory rate 20 breaths per minute or PaCO2 32 mmHg or mechanical

ventilation

White blood cell count 12,000/L or 4000/L or 10% band forms

Sepsis Identifiable source of infection + SIRS

Severe sepsis Sepsis + organ dysfunction

Septic shock Sepsis + cardiovascular collapse (requiring vasopressor support)

• Non-specific response of the body to variety
of stressors (trauma,surgery,burn,sepsis,
starvation..)
• severe injury, infection, trauma, and major
surgery are serious conditions that cause
profound physiological changes.
• Response to injury is graded : the more severe
the injury, the greater the response
• The Aim:
– Identify and quantify the injurious agent.
– Maintain Critical Organ function
– Restore Homeostasis
– Mobilize Energy reserves
– Provide substrate for tissue repair
– Repair of dysfunctional tissue
– Eradicate sepsis
Factors influencing the Extent and Duration of the Metabolic
Response

• Pain and Fear

• Surgical Factors:
– Type of surgery
– Region
– Duration
• Preoperative support
• Extent of the trauma and degree of
resuscitation
• Post traumatic complications:
– Hemorrhage
– Hypoxia
– Sepsis and Fever
– Starvation
– Re-operation
• Pre-existing nutritional status
 Response components

• Central Nervous System(neuronal)

• Hormonal Response
• Immunologic response
• Cellular Response
 Central Nervous System(neuronal
response
• Injury signals are recognized by the CNS
through afferent signal pathways.
• respond through both circulatory and
neuronal pathways (efferent pathways).
• NOCICEPTORS :pain-producing substances
(algogens) are released following injury.
 ATP, bradykinin, histamine, serotonin (5-
HT), hydrogen ions, and a number of
inflammatory mediators such as
prostaglandins.
• transmission of stimuli to spinothalamic tracts
and cortex
• Mediators produced by cells of the
wound(cytokines ,PAF ,complement factor )
 autocrine, paracrine, remote endocrine
function stimulate hypothalamus-
pituitaryadrenal axis
 hypothalamic-pituitary-adrenal axis
• mediators:
– ACTH: cortisol
– ADH
– catecholamines: epinephrine
norepinephrine
– glucagon
• Adrenocorticotropic Hormone (ACTH)
-diurnal pattern becomes blunted (graded
response).
- stimuli for ACTH release:
 CTRH, pain, anxiety, vasopressin,
angiotensin II , vasoactive intestinal
polypeptide, catecholamines, and
proinflammatory cytokines
• Cortisol
 liver: decrease glycogenesis, while increasing
gluconeogenesis.
 skeletal muscle, cortisol facilitates the
breakdown of protein
 adipose tissue cortisol stimulates the release
of free fatty acids, triglycerides, and glycerol.
 Wound healing also is impaired
 immunosuppressive
• Catecholamines: epinephrine, norepinephrine
 After severe injury, plasma catecholamine
levels are increased threefold to fourfold
 elevations lasts 24 to 48 hours
• Epinephrine induce
 gluconeogenesis , glycogenolysis ,lipolysis and
proteolysis.
 promotes insulin resistance in skeletal muscle
 Immunomodulation(inhibit the release of
inflammatory cytokines,TNF, IL-1, and IL-6)
 increased cardiac oxygen demand,
vasoconstriction, and increased cardiac output
• ANTIDIURETIC HORMONE (ADH)
-released from neurohypophysis
- leads to water conservation
- stimuli: decreased effective blood volume,
angiotensin II
• glucagon: substrate mobilisation
– glycogenolysis
– gluconeogenesis
– lipolysis
– ketogenesis
• Hyperglycemia and insulin resistance are
hallmarks of critical illness.
 due to the catabolic effects of circulating
mediators, including catecholamines, cortisol,
glucagon, and growth hormone.
Hormonal Pituitary Adrenal Pancreatic Others
change

Increased Growth hormone (GH) Adrenaline Glucagon Renin

secretion Adrenocorticotrophic Cortisol Angiotensin
hormone Aldosterone
Prolactin
Antidiuretic hormone
Unchanged Thyroid-stimulating
secretion hormone (TSH)
Luteinizing hormone
(LH)
Follicle-stimulating
hormone (FSH)
Decreased insulin Testosterone
secretion Oestrogen
Thyroid
hormones
 IMMUNOLOGIC RESPONSE

• Stress hormones and mediators influence

immune modulation.
• Specific / cell mediated immunity is depressed
 inhibition of T-cell proliferation and shift in
TH2-cell direction (antiinflammatory)
• Non-specific immune system is activated
• cells of wound produce cytokines
( monocytes, macrophages)
• TNF stimulates muscle breakdown and
cachexia
 increased catabolism, insulin resistance,
and redistribution of amino acids to hepatic
circulation as fuel substrates.
• IL-1 : inflammatory sequence similar to that of
TNF.
- endogenous pyrogen
• IL-6 has counterregulatory effects on the
inflammatory cascade through the inhibition
of TNF and IL-1.
 Cellular Response
• migration of platelets and neutrophils
• procoagulant shift
 decreased production of anticoagulant
factors
 microthrombosis and organ injury.
• predominance of TH2 over TH1
The immune response
Metabolic Response to Trauma/stress
• The initial hours: reduced total body energy
expenditure and urinary nitrogen wasting.
• adequate resuscitation and stabilization of the
injured patient
• Ebb Phase
• Immediately following injury
• For 24 to 48 hrs
• Associated with shock & resuscitation
• Oxygen consumption 
Oxygen delivery to the tissue 
• Sympathetic nervous system 
hypothalamic-pituitary axis 
 Ebb phase
Phenomenon Effect

 blood glucose
 catecholamine
 lactate
 glucagon
free fatty acids

 cardiac output

 oxygen consumption
Below normal core
temperature
• Succumb from lack of oxygen and nutrient
supply to major organs
• Survive if prompt resuscitation is given
Flow phase
Phenomenon Effect

 catecholamine  consumption
 glucagon
N or 
of glucose,
 cortisol glucose
FFA, amino
 insulin N or  FFA acid
normal
lactate
 cardiac output  CO2 production
 O2 consumption
 core body  heat production
temperature
 aldosterone
fluid retention
 ADH

IL1, IL6, TNF systemic multi-

spillage from inflammatory organ
wound response failure
• Metabolism after Injury
• Injuries or infections induce unique
neuroendocrine and immunologic responses
that differentiate injury metabolism from that
of unstressed fasting
Carbohydrate Metabolism:
Hyperglycemia:
Increased catecholamine (primarily), cortisol,
glucagon, GH, vasopressin, angiotensin II,
somatostatin and decrease insulin.
Gluconeogenesis in liver and kidney and
impaired peripheral uptake of glucose
Lipid metabolism:
– primary source of energy during critical illness and
after injury (50 to 80%).
– Best stimulus for hormone-sensitive lipase is
catecholamine
• Water Balance
– Under the influence of ADH
– Results in WATER RETENTION.
• Sodium Balance
– Early Retention
– Plasma levels: normal/ raised
• Potassium Balance
– Initial Decrease
– The raised b/c of Intracellular K is released by injured
tissue
 Methods to decrease the response to injury
• prompt operative care
-correct blood loss
-repair injured organs
careful surgical technique
-reduces load of necrotic tissue
-minimizes risk of postoperative infection
 debridement
 irrigation
 stop contamination
• minimal surgical procedures
 damage control surgery
• epidural or spinal anesthesia
 blocking afferent pain stimuli
 attenuation of hormonal response
• nutritional support
 decreases total protein loss
 start enteral feeding whenever possible
• hormone manipulations
 may have some positive effects
 not recommended for general use