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Pathophysiology
Multiple Organ Dysfunction Syndrome
Pathophysiology Department, Tongji Medical College, HUST
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World War OneCirculatory failure, hypovolemic shock
World War TwoKorean War
Post-traumatic acute renal insufficiency
Viet Nam War Post-traumatic acute
respiratory insufficiency
Seventy’s70’s syndrome
1991Multiple organ dysfunction syndrome
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Left leg open trauma
Day 2: Shortness of breath, Oliguria
Day 4:T 39.5 ℃↑WBC (18×109/L) ↑↑R 35 /m, cyanosis, PaO2<60mmHgUrine <100ml/dCreatinine ↑↑ BUN ↑↑
Renal failure
Respiratory failure
Day 6: Death
Case reportCase report
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Pathophysiology
Multiple Organ Dysfunction Syndrome (MODS)
is dysfunction of two or more organs (initially
uninvolved developing within a short period of
time.
short period
two or more organs initially
DefinitionDefinitionDefinitionDefinition
uninvolved
Cor pulmonale?
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Multiple system organ failure. The role of uncontrolled
infection .
They studied multiple parameters in
553 consecutive emergency surgical
patients.MSOF is primarily due to infection.MSOF is the most common fatal
expression of uncontrolled infection.
1980,115(2):136-140.
CausesCausesCausesCauses
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Pathophysiology
Why did anti-biotic strategies fail in some
of the patients with MODS?
Why did anti-biotic strategies fail in some
of the patients with MODS?
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MODSMODS
Biliary tract infection
Shock
Pancreatitis
BurnBurn
Intra-abdominal infection
Infective diseases Non-infective diseases
Multiple trauma
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Pathophysiology
MODSMODS
Biliary tract infection
Shock
Pancreatitis
BurnBurn
Intra-abdominal infection
Infective diseases Non-infective diseases
Multiple trauma
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Pathophysiology
Bacterial translocation
The viable bacili locomote from the gastrointestinal tract to the other organs.
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Pathophysiology
Intestinal flora imbalanceImmune dysfunctionIntestinal mucosal ischemia
Causes for the translocation
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Pathophysiology
What exactly is "leaky gut" or "increased intestinal permeability"?
To understand the importance of increased intestinal permeability, you must first understand the basic concepts that: 1) the intestines are supposed to absorb nutrients, and 2) the intestines are supposed to exclude (not absorb) potentially harmful substances like bacteria, toxins, food proteins (which cause food allergy).
Therefore, when we talk about "leaky gut" and "increased intestinal permeability" we are describing a condition where in these basic functions are failing. The intestines are failing in the ability to absorb nutrients, and the intestines are absorbing too many toxins.
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Pathophysiology
Infective diseases Non-infective diseases
MODS
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Pathophysiology
Ischemia/reperfusion injury
MechanismMechanism
Uncontrolled inflammatory response
Microcirculatory hypo-perfusion
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Pathophysiology
Causes
MODSMODS
Uncontrolled inflammatory response
Q1
Q2
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Pathophysiology
Inflammation
Inflammatory cells
Inflammatory cytokines
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Pathophysiology
Pro-inflammatory reactionTNF-a, IL-1, IL-6, IFN
TXA2, PAFCell activation
Anti-inflammatory reactionIL-10, IL-4, TGF-β
IL-1ra ,LipoxinCell elimination
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Pathophysiology
MODS is the failure of the balance
Uncontrolled inflammatory response
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Pathophysiology
Systemic Inflammatory Response Syndrome (SIRS)
An uncontrolled inflammation processPro-inflammatory signals exceed its normal domain or degree
Result in end-organ damage and multi-system failure.
【 Definition】
Anti-inflammatory reactionIL-10, IL-4, TGF-β
IL-1ra ,LipoxinCell eliminate
Pro-inflammatory reactionTNF-a, IL-1, IL-6, IFN
TXA2, PAFCell activation
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Infection/ injury
Local inflammatory cell activated
(M,PMN,VEC,),PMN,VEC,)
Pro-inflammatory mediators released
Inflammatory stimulator
Tissue injury
Systemic inflammatory cell activated
(M,PMN,VEC,),PMN,VEC,)
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Pathophysiology
【 SIRS Clinical manifestations 】
Body temperature above 38 or less than 36 . ℃ ℃
Heart rate >90 beat/min.
Respiration rate >20/min or PaCO2 <32 mmHg.
WBC >12,000/mm3 or <4000 cells/mm3, or >10%
immature cells.
above 38℃
>20/min
>12,000/mm3
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Pathophysiology
SIRS
Renal failureRespiratory failure
Left leg open trauma
Case reviewCase review
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Pathophysiology
Compensatory Anti-inflammatory Response Syndrome( CARS)
An uncontrolled anti-inflammation processAnti-inflammatory signals exceed its normal domain or degree Result in end-organ damage and multi-system failure.
【 Definition】
Immune paralysis
Anti-inflammatory reactionIL-10, IL-4, TGF-β
IL-1ra ,LipoxinCell eliminate
Pro-inflammatory reactionTNF-a, IL-1, IL-6, IFN
TXA2, PAFCell activation
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Pathophysiology
SIRS CARS
MODS
Uncontrolled inflammatory response
Infection/Injury
Controlled inflammatory response
Infection/injury controlled
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Pathophysiology
Infection/Injury
Host response
SIRS CARS
MODS
Uncontrolled inflammatory response
Excessive
Adequate
Death
Inadequate
Infection/injury controlled
SummarySummary
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Pathophysiology
Alternations in Functions and Mechanism in different organs
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Pathophysiology
Respiratory systemAlveolar epithelial cell swelling lack of surfactant
WBC assembling phagocytosis
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Pathophysiology
Respiratory
circulation
Systemic circulation
superior vena cavainferior vena cava
Mechanism Highest incidence earliest occurring
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Pathophysiology
WBC Leukotriene
Permeability
Neutrophils adhesion
WBC assembling
Main manifestation
Pulmonary edema pulmonary hemorrhage Dyspnea death
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Pathophysiology
Urinary system
Acute renal failure
MechanismAcute necrosis of tubular cellsDecreased perfusion of kidney
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Pathophysiology
Hepatic changes
Trauma,infection
Hepatic dysfunctionBody injury
Icterus Hepatic failure
①Elimination of ET
②Production of energy
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Pathophysiology
““ No great discovery No great discovery was ever made without was ever made without
a bold guess.”a bold guess.”
Isaac Newton (1642-1727)
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Pathophysiology
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