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