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Transcript
Pathophysiology
Multiple Organ Dysfunction Syndrome
Pathophysiology Department, Tongji Medical College, HUST
World War One
Circulatory failure, hypovolemic shock
World War Two
Korean
War
Viet
Nam War
Post-traumaticacute
acute
Post-traumatic
renal insufficiency
respiratory
insufficiency
Seventy’s
70’s syndrome
1991
Multiple organ dysfunction syndrome
Case report
Left leg open trauma
Day 2:
Shortness of breath, Oliguria
Day 4:
9/L) ↑
T 39.5 ℃↑WBC
(18×10
Respiratory failure
R 35 /m, cyanosis, PaO2<60mmHg
Urine <100ml/d
Renal failure
Creatinine ↑↑ BUN ↑↑
Day 6:
Death
Pathophysiology
Definition
Multiple Organ Dysfunction Syndrome (MODS)
is dysfunction of two
organs (initially
two or more organs
initially
uninvolved developing within a short
short period
period of
time.
Cor pulmonale?
Causes
Multiple system organ failure.
The role of uncontrolled infection .
1980,115(2):136-140.
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.
Pathophysiology
Why did anti-biotic strategies
fail in some
of the patients with MODS?
Intra-abdominal
infection
Shock
MODS
Pancreatitis
Multiple trauma
Biliary tract
infection
Infective diseases
Burn
Non-infective diseases
Pathophysiology
Intra-abdominal
infection
Shock
MODS
Pancreatitis
Multiple trauma
Biliary tract
infection
Infective diseases
Burn
Non-infective diseases
Pathophysiology
Bacterial translocation
The viable bacili locomote from the
gastrointestinal tract to the other organs.
Causes for the translocation
Intestinal flora imbalance
Immune dysfunction
Intestinal mucosal ischemia
Pathophysiology
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
Mechanism
Uncontrolled inflammatory response
Microcirculatory hypo-perfusion
Ischemia/reperfusion injury
Pathophysiology
Causes
Q1
Uncontrolled inflammatory response
Q2
MODS
Pathophysiology
Inflammation
Inflammatory cells
Inflammatory cytokines
Pathophysiology
Anti-inflammatory reaction
IL-10, IL-4, TGF-β
IL-1ra ,Lipoxin
Cell elimination
Pro-inflammatory reaction
TNF-a, IL-1, IL-6, IFN
TXA2, PAF
Cell activation
Pathophysiology
MODS is the failure of the balance
Uncontrolled inflammatory response
Pathophysiology
Systemic Inflammatory Response Syndrome (SIRS)
【Definition】
Anti-inflammatory reaction
IL-10, IL-4, TGF-β
IL-1ra ,Lipoxin
Cell eliminate
An uncontrolled inflammation process
Pro-inflammatory signals exceed its normal
domain or degree
Pro-inflammatory reaction
TNF-a, IL-1, IL-6, IFN
TXA2, PAF
ResultCell
in activation
end-organ damage
failure.
and multi-system
Infection/ injury
Pro-inflammatory
mediators released
Inflammatory stimulator
Local inflammatory
Systemic
inflammatory
cell
cell activated
activated
(M,PMN,VEC,)
(M,PMN,VEC,)
Tissue injury
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.
Pathophysiology
Case review
Left leg open trauma
SIRS
Respiratory failure
Renal failure
Pathophysiology
Compensatory Anti-inflammatory Response Syndrome( CARS)
【Definition】
Anti-inflammatory reaction
IL-10, IL-4, TGF-β
IL-1ra ,Lipoxin
Cell eliminate
anti-inflammation
process
An uncontrolled
Anti-inflammatory signals exceed its normal
domain or degree
Result in end-organ damage and multi-system
failure.
Pro-inflammatory reaction
TNF-a, IL-1, IL-6, IFN
TXA2, PAF
Cell activation
Immune paralysis
Pathophysiology
Infection/Injury
Uncontrolled
inflammatory response
SIRS
Controlled
inflammatory response
CARS
MODS
Infection/injury
controlled
Pathophysiology
Summary
Infection/Injury
Adequate
Host
response
Infection/injury
controlled
Excessive
Death
Uncontrolled
inflammatory response
SIRS
CARS
MODS
Inadequate
Pathophysiology
Alternations in Functions
and Mechanism in different organs
Pathophysiology
Respiratory system
Alveolar epithelial cell swelling
lack of surfactant
WBC assembling
phagocytosis
Pathophysiology
Highest incidence
earliest occurring
Mechanism
inferior vena cava
superior vena cava
Respiratory
circulation
Systemic circulation
Pathophysiology
Permeability
WBC
Leukotriene
Neutrophils adhesion
WBC assembling
Main manifestation
Pulmonary edema
pulmonary hemorrhage
Dyspnea
death
Pathophysiology
Urinary system
Acute renal failure
Mechanism
Acute necrosis of tubular cells
Decreased perfusion of kidney
Pathophysiology
Hepatic changes
Trauma,infection
Body injury
Hepatic dysfunction
①Elimination of ET
②Production of energy
Icterus
Hepatic failure
Pathophysiology
Isaac Newton
(1642-1727)
“No great discovery was ever made
without a bold guess.”
Pathophysiology
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