SYSTEMIC INFLAMMATORY

RESPONSE SYNDROME

SIRS: 2 or more of following

Fever of more than 38C (100.4F) or less than
36C (96.8F)
Heart rate of more than 90 beats per minute
Respiratory rate of more than 20 breaths per
minute or arterial carbon dioxide tension
(PaCO 2) of less than 32 mm Hg
Abnormal white blood cell count
(>12,000/L or < 4,000/L or >10% immature [band]
forms)

 Non Specific: May be Caused by

TRAUMA

BACTERIA
BURNS

INFEC
TION

sepsis
SIRS

ISCHEMIA

P
V

OTHERS

Counterregulatory Anti Inflam.

Response Syndrome

REGULATORS OF SIRS

CNS

HORMONAL

ACTH
Binds to receptors of Zona Fasciculata of adrenal
gland GLUCOCORTICOID

Cortisol and Glucocorticoids

in states of stress
Hyperglycemia
Impaired wound healing
Immunosupressive
Anti inflammatory

Macrophage Migration Inhibiting Factor

Counterregulates excessive anti inflammatory
and immunosupressive actions of Cortisol in
times of stress
Thus , increasing immune response against
Pathogens, if present

Catecholamines

NE, Epi ,Dopa increase 3-4 fold 24-48 hours

Induce catabolic states and hyperglycemia
Inhibit inflam cytoknes TNF, IL1 and IL-6,
increases anti inflam cytokine --IL -10

GH and IGF
Promote CHON synthesis, lopogenesis and
glycogenesis
enhance phagocytic activity of immunocytes

Insulin
Hyperglycemia and Insulin resistance
Hallmarks of critical illness due to catabolic
effects of circulating mediators
Promotes further immunosupressive effects , dec
phagocytosis and increased risk for infection

MEDIATORS of SIRS

CYTOKINES
Class of protein signaling compounds for innate
and adaptive immune responses
Mediate broad sequence of cellular responses
Mediate eradication of invading micro
organisms but exaggerated responses result in
hemodynamic instability (septic shock) and
metabolic derangements.

EICOSANOIDS

SEROTONIN
stimulates vasoconstriction,
bronchoconstriction, and platelet aggregation
blockade is associated with decreased
production of TNF and interleukin-1

HISTAMINE

H1 vasodilaton, bronchoconstriction,
H2 gastric parietal cell acid secretion
H3 auto receptor , downregulates H
H4 in eosinophils and mast cells

CELL Signaling
G- Protein- cAMP pathway and IP3 pathway
epinephrine , bradykinin, leukotriene
Ligand gated Ion Channels - Neurotransmitters,
amino acids, ach
Tyrosine Kinases signalling for several
growth and endothelial growth factor. IGF,EGF,
VEGF
Janus Kinase mediate signal transduction of
cytokines

CELL-Mediated Inflam Response

Platelets
Activated platelets at the site of injury release
inflammatory mediators that serve as the
principal chemoattractant for neutrophils and
monocyte

Lymphocytes
B and T cells which are mediators of adaptive
immunity.
Secrete cyokines that promotes inflam cascades

Eosinophils
Activated by IL3 and 5. mainly antihelmintic

Mast Cells
Role in anaphylactic response to allergens
TNF released from Mast cells Neutrophil recruitment

Monocytes
Differentiates into macrophages, osteclasts and dendritic
cells.
Main effector cells of the immune response to infection
and injury

Neutrophils
First responders to sites of infection/injury
Potent mediators of acute inflammation.

ENDOTHELIUM-MEDIATED INJURY
VASCULAR ENDOTHELIUM
- overall anticoagulant properties
- BUT in Sepsis/injury becomes
procoagulant microthrombosis and organ
injury

Neutrophil-Endothelium Interaction

NO
Maintains smooth muscle relaxation

PROSTACYCLIN

Potent vasodilator and inhibits platelet

aggregation

PAF
Further activates Platelets and neutrophils and
increase vascular permeability

END