Pathophysiology

Multiple Organ Dysfunction Syndrome

Pathophysiology Department, Tongji Medical College, HUST

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

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

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?

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

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?

MODSMODS

Biliary tract infection

Shock

Pancreatitis

BurnBurn

Intra-abdominal infection

Infective diseases Non-infective diseases

Multiple trauma

Pathophysiology

MODSMODS

Biliary tract infection

Shock

Pancreatitis

BurnBurn

Intra-abdominal infection

Infective diseases Non-infective diseases

Multiple trauma

Pathophysiology

Bacterial translocation

The viable bacili locomote from the gastrointestinal tract to the other organs.

Pathophysiology

Intestinal flora imbalanceImmune dysfunctionIntestinal mucosal ischemia

Causes for the translocation

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.  

Pathophysiology

Infective diseases Non-infective diseases

MODS

Pathophysiology

Ischemia/reperfusion injury

MechanismMechanism

Uncontrolled inflammatory response

Microcirculatory hypo-perfusion

Pathophysiology

Causes

MODSMODS

Uncontrolled inflammatory response

Q1

Q2

Pathophysiology

Inflammation

Inflammatory cells

Inflammatory cytokines

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

Pathophysiology

MODS is the failure of the balance

Uncontrolled inflammatory response

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

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,)

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

Pathophysiology

SIRS

Renal failureRespiratory failure

Left leg open trauma

Case reviewCase review

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

Pathophysiology

SIRS CARS

MODS

Uncontrolled inflammatory response

Infection/Injury

Controlled inflammatory response

Infection/injury controlled

Pathophysiology

Infection/Injury

Host response

SIRS CARS

MODS

Uncontrolled inflammatory response

Excessive

Adequate

Death

Inadequate

Infection/injury controlled

SummarySummary

Pathophysiology

Alternations in Functions and Mechanism in different organs

Pathophysiology

Respiratory systemAlveolar epithelial cell swelling lack of surfactant

WBC assembling phagocytosis

Pathophysiology

Respiratory

circulation

Systemic circulation

superior vena cavainferior vena cava

Mechanism Highest incidence earliest occurring

Pathophysiology

WBC Leukotriene

Permeability

Neutrophils adhesion

WBC assembling

Main manifestation

Pulmonary edema pulmonary hemorrhage Dyspnea death

Pathophysiology

Urinary system

Acute renal failure

MechanismAcute necrosis of tubular cellsDecreased perfusion of kidney

Pathophysiology

Hepatic changes

Trauma,infection

Hepatic dysfunctionBody injury

Icterus Hepatic failure

①Elimination of ET

②Production of energy

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)

Pathophysiology

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