Systemic Inflammatory
Response Syndrome (SIRS)
and
Multi-system Organ
Dysfunction Syndrome
(MODS)
SIRS
Systemic Inflammatory Response Syndrome
Sepsis
SIRS with objective signs of bacteremia
MODS
Multi-system Organ Dysfunction Syndrome
(was: Multiple Organ Failure)
2 or more systemic-organs involved
Shock
lack of perfusion
Septic shock
Sepsis with hypotension despite of an
adequate fluid resuscitation
Severe Sepsis
Sepsis associated with organ dysfunction
The Process of Inflammation:
body response to injury
Local [tissue] response to injury
Vascular component
Cellular component
Hemostatic reaction
Diagram of Spiess
Interaction of hemostasis and inflammation
Endothelial response
Platelets aggregations
Leukocytes adhesion
Constriction of the vessels
Cellular involvements
Inflammatory mediators
Clotting
Acute Inflammation
Capillary permeability & leakage
Normal
Increased permeability
Capillary Osmotic Pressure
Pressure of Proteins
Blood Capillary
25-30mmHg 25-30mmHg
Tissue Osmotic Pressure
Pressure of Proteins Interstitial fluid
[variable] [variable]
Lymph
Composition same as Lymphatic Capillary
Interstitial fluid
Net HP = HPc – HPif Net HP = HPc – HPif
= 25 – 1 mmHg = 15 – 1 mmHg
= 24mmHg = 14mmHg
Arteriol Venula
Blood Capillary
HPc 25mmHg HPc 15mmHg
HPif 1mmHg HPif 1mmHg Interstitial fluid
Lymphatic Capillary
Net HP = HPc – HPif Net HP = HPc – HPif
= 25 – 1 mmHg = 5 – 3 mmHg
= 24mmHg = 2mmHg
Arteriol Venula
Blood Capillary
HPc 25mmHg HPc 5mmHg
HPif 1mmHg HPif 3mmHg Interstitial fluid
Overload!!! Lymphatic Capillary
The nature of normal response to injury
in acute phase
Immune response to injury
Acute inflammation Healing
3-5 days time
5-21 days
pro-inflammatory anti-inflammatory
Pathophysiology of SIRS
Trauma
Predisposing factor
Activator
Inflammatory mediators Inflammatory
mediators↑↑↑
Acute Inflammation SIRS
Heal MODS Death
Systemic Inflammatory Response Syndrome
Systemic response to various clinical stimuli :
Infection Bacteria, viral, toxins
Trauma Shock (hemorrhagic, hypovolemia)
Malignancy
Degenerative Exhaustion
Autoimmune response Debils
Predisposing factors
Systemic Inflammatory Response Syndrome
Infection
Bacteremia Trauma
Viremia Sepsis SIRS Burns
Fungemia Ischemia
Parasitemia Pancreatitis
Systemic Inflammatory Response Syndrome
Activators :
Infection
Trauma Uncontrolled
Inadequate perfusion Pro
Ischemic/necrotic tissue Inflammatory
Reperfusion injury mediators
Precipitating factors
Systemic Inflammatory Response Syndrome
SIRS
Immune response to injury
Exaggerative response
3-5 days time
5-21 days
pro-inflammatory anti-inflammatory
32 days
• recruitment neutrophil
• arachidonic acid production
• free radicals
Systemic Inflammatory Response Syndrome
Trauma
Acute Inflammation
Catabolism Shock Tissue damage
Toxins Infection
Inadequate
blood flow
Cerebral Cardiac Pulmonary Splanchnic Renal Muscular etc
Deteriorated Systemic Circulation
Early phase Second phase
Inadequate blood flow Stable Hemo-dynamic
[Lack of perfusion]
Inefficient utilization of
Tissue hypoxia macronutrient
Anaerobe Metabolic changes
metabolism
Lean body mass
breakdown
ATP ▼
Ebb phase Flow phase
Hypo-metabolic stage Hyper-metabolic stage
Trauma
Shock
Tissue damage
[systemic perfusion▼]
Endothelial disruptions Epithelial disruptions
Pro inflammatory mediators
Pro inflammatory mediators: Cytokines
Primary
tumor necrotizing factor (TNF), interleukin (IL1, IL6), interferon,
colony stimulating factor (CSF)
Secondary
prostaglandin, leukotriene, thromboxane, platelet activating factor
(PAF), free radicals, nitric oxide, proteases (cathepsin, elastase)
Positive: Reconstructive Negative: Destructive
Phase I
Etiology
(Trauma, etc)
Predisposing Precipitating
factor[s] factor[s]
Local Response
Cytokines
Macrophages Endothelial
Phase II
Systemic
Response
Deteriorated Homeostasis
Phase III
SIRS
Metabolic Hematology Cerebral Hepatic Cardiac Renal Pulmonary Gut
Endocrine
MODS
…more about SIRS
Pro Inflammatory Anti Inflammatory
mediators mediators
The Resultants
…more about SIRS
Pro Inflammatory mediators
Exaggerated response lead to Systemic Inflammatory Response
Syndrome (SIRS)
Destructive
Anti Inflammatory mediators
Exaggerated response lead to Compenstaed Anti-inflammatory
Response Syndrome (CARS)
Destructive
SIRS vs. CARS
…more about SIRS
Pro-Inflammatory
Anti-Inflammatory
CARS
CARS
CARS
SIRS
SIRS
SIRS
a b
Physiologic I SIRS II CARS III MARS
a) SIRS dominant
b) CARS dominant
The cascade of SIRS: competition between SIRS and CARS
Systemic Inflammatory Response Syndrome
Tissue injury
ARDS SIRS
Immune response to injury
Exaggerative response CARS
Immune suppression
sepsis
3-5 days >8-10days time
5-21 days
pro-inflammatory anti-inflammatory
32 days
• recruitment neutrophil
• arachidonic acid production
• free radicals
Pro Inflammatory response The Etiology Anti Inflammatory response
[local] [local]
Pro Inflammatory response Systemic Response Anti Inflammatory response
[ systemic ] [ systemic ]
SIRS
CARS
MARS
Cardiovascular Organ Immune
Homeostasis Apoptosis suppression
compromised dysfunction
SIRS Predominant Equal CARS-SIRS SIRS Predominant SIRS Predominant CARS Dominant
C H A O S
CARS Compensatory Anti-inflammatory Response Syndrome
MARS Mixed Antagonistic Response Syndrome
The Etiology
SIRS CARS MARS
C H A O S
MODS
MOF
Cardiovascular compromised Myocardial infarct
Pro Inflammatory mediator ►Myocardial Depressant Factor (MDF)
Organ dysfunction: Pulmonary Acute Respiratory Distress Syndrome
Pro Inflammatory mediator ►Neutrophil recruitment↑↑
Organ dysfunction: Pulmonary Acute Respiratory Distress Syndrome
Pro Inflammatory mediator ►Neutrophil recruitment↑↑
O2 CO2
O2 CO2
Organ dysfunction: Pulmonary Acute Respiratory Distress Syndrome
Pro Inflammatory mediator ►Neutrophil recruitment↑↑
Prolonged ALI Precipitating factors
Leads to ARDS
Pulmonary Neutrophil
inflammation recruitment
with edema &
vasoconstriction
Diminished oxygen Pro Inflammatory
exchange Eicosanoic, free radicals
ARDS: Phase 1
ARDS: Phase 2
ARDS: Phase 3
ARDS: Phase 4
ARDS: macroscopic
ARDS: consolidation
ARDS: the infiltrates (post-mortem)
Acute Respiratory Distress Syndrome
ARDS has no correlation with lung
infection: clearly it is not a problem of
infection
The patophysiology of ARDS has a
close relationship with the degree of
tissue damage as well as the necrotic
tissue (reflected by the percentage of
TBSA & wound depth), the causes
(burn, electric, chemical, scald),
multiple and existing inhalation injury.
Hinshaw, LB, Lee, PA, Pryor, RW, Pathogenesis and therapy of the multi-system organ failure. In Pollock, AV. Immunonolgy in
surgical practice. London-Melbourne-Auckland: Edward Arnold, 1991; 350.
Acute Respiratory Distress Syndrome
Bilateral infiltrate Honeycomb appearance
[ARDS] [Pneumonia]
The Criteria of SIRS
American College of Chest Physicians and the Society of Critical Care Medicine
2 or more clinical entities listed below:
Hyperthermia ( > 38 C) or hypothermia ( < 36 C)
Tachycardia (pulse rate > 90 times per minute)
Tachypnea (> 20 times per minute) or low PCO2 (< 32 mmHg)
Leucocytes > 12000 cells per mm3 or leucopenia (< 4000 cells per
mm3) or, more than 10% immature neutrophyl (band).
The Criteria of MODS
Knauss et al
1 or more clinical entities listed:
Cardiovascular failure
Heart Rate < 54 beats/minutes
Mean Arterial Pressure <49mmHg
Ventricular tachycardia, ventricular fibrilation, or both
serum pH <7.24 with PaCO2 <49mmHg
The Criteria of MODS
Knauss et al
1 or more clinical entities listed:
Respiratory failure
Respiratory Rate < 5 or > 49 times/minute
PaCO2 >50mmHg
AaDO2 >350mmHg (AaDO2 = 713 FiO2 – PaCO2 – PaO2)
Mechanical ventilator dependence by fourth day to diagnosis of
organ failure (notice: such criteria is not acceptable to failure in
the first 72hr)
The Criteria of MODS
Knauss et al
1 or more clinical entities listed:
Renal failure
Urine output < 479ml/24hr or <159ml/8hr
Blood Urea Nitrogen >100mg/dl
Serum Creatinine > 3.5mg/dl
The Criteria of MODS
Knauss et al
1 or more clinical entities listed:
Haematology failure
WBC count < 1000/mm3
Platelet < 20.000 cell/mm3
Hematocryte < 20%
The Criteria of MODS
Knauss et al
1 or more clinical entities listed:
Neurology failure
GCS <6 (without sedation)
The Criteria of MODS
Goris et al
Scoring system to MODS:0 = None, 1 = Moderate, 2 = Severe
Pulmonary failure
0 = No mechanical ventilator needed
1 = Mechanical ventilator with PEEP 10cm H2O and/or FiO2 < 0.4
2 = Mechanical ventilator with PEEP >10cm H2O and/or FiO2 > 0.4
The Criteria of MODS
Goris et al
Scoring system to MODS:0 = None, 1 = Moderate, 2 = Severe
Cardiac failure
0 = Normal Blood Pressure without vaso-active agent assistance
1 = Periods of hypotension needs manipulation to maintain
BP>100mmHg, such as volume loading, or vaso-active agent
(dopamine <10µg/kg/minute or nitroglycerin <20µg/kg/minute )
2 = Periods of hypotension needs manipulation to maintain
BP>100mmHg, such as volume loading, or vaso-active agent
(dopamine >10µg/kg/minute or nitroglycerin >20µg/kg/minute )
The Criteria of MODS
Goris et al
Scoring system to MODS:0 = None, 1 = Moderate, 2 = Severe
Renal failure
0 = Normal serum cretinine (<20mg/dl)
1 = Serum creatinine >20mg/dl
2 = Either hemodyalisis or peritoneal dyalisis is needed
The Criteria of MODS
Goris et al
Scoring system to MODS:0 = None, 1 = Moderate, 2 = Severe
Hepatic failure
0 = SGOT <25unit/L, Bilirubin <2mg/dl
1 = SGOT >25<50unit/L, Bilirubin >2mg/dl <6mg/dl
2 = SGOT >50unit/L, Bilirubin >6mg/dl
The Criteria of MODS
Goris et al
Scoring system to MODS:0 = None, 1 = Moderate, 2 = Severe
Haematology failure
0 = Normal leucocyte and platelet count
1 = Leucocyte >30X106/L <60X106/L, platelet <50X109/L
2 = Leucocyte <2.5 X106/L or >60X106/L, diathesis hemorrhagic
The Criteria of MODS
Goris et al
Scoring system to MODS:0 = None, 1 = Moderate, 2 = Severe
Gastrointestinal Tract failure
0 = Normal function
1 = Stress ulcer or acalculous cholesistitis
2 = Stress ulcer which >2U blood transfusion needed within 24hr,
necrotizing enterocolitis, pancreatitis, spontaneous perforation of
gallblader
The Criteria of MODS
Goris et al
Scoring system to MODS:0 = None, 1 = Moderate, 2 = Severe
Central Nervous System failure
0 = Normal function
1 = Lowering response
2 = Disturbances of response with neuropathy
The Management
Principles in The Management of SIRS & MODS
Awareness the problems of the victims with deep of empathy, never
disobey any clinical entity but know the mechanism as well i.e.
Total Care
Do the right things and do the things right
The resuscitation and its monitoring, maintain the perfusion in
short time period
Early detection of any organic malfunctions
Damage control at the first change
Stop the nature of destruction, eliminate the infection and all
hazardous stuff
Don No harm
Keep on your mind the main principles of surgery, so does a
surgeon