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Lecture: “The Inflammatory Cascade” by Dr. Geert Schmid-Schonbein, part I.
Given August 7, 2006 during the GEM4 session at MIT in Cambridge, MA.
Please use the following citation format:
Schmid-Schonbein, Geert. “The Inflammatory Cascade, Part I.” Lecture,GEM4 session at MIT, Cambridge, MA, August 7,
2006. http://gem4.educommons.net/ (accessed MM DD, YYYY). License: Creative Commons Attribution-NoncommercialShare Alike.
Note: Please use the actual date you accessed this material in your citation.
The Inflammatory Cascade:
Shock and Multi-organ Failure
Image removed due to copyright restrictions.
Please see Fig. 4 in Schmid-Schonbein, et al. Microvascular Networks: Theoretical and Experimental
Studies. Farmington, CT: S. Karger, 1986, p. 44.
Pressure-Flow Relationship in Skeletal Muscle Microcirculation
1.0
Braakman, 1988
Pappenheimer
and Maes, 1942
Flow, Q (m1/min-gm)
0.8
0.6
Sutton, 1987
0.4
Theory:
Newtonian fluid
0.2
Non-Newtonian fluid
0.0
0
20
40
60
80
100
120
Pressure Drop, Pa - Pv (mm-Hg)
Figure by MIT OpenCourseWare.
Cardiovascular Disease is Accompanied
By Cell Activation and Inflammation
• • • • • • • • • • Infectious Diseases
Chronic Degenerative Diseases
(arthritis, retinopathy, dementia,
venous disease, coeliac disease, … )
Diabetes
Cardiovascular Risks (smoking, obesity)
Myocardial ischemia
Stroke
Atherosclerosis
Arterial Hypertension
Cancer
Physiological Shock
The Inflammatory Cascade
Early Cell Responses:
Trigger mechanism
Ion exchange
Pseudopod formation by actin polymerization/depolymerization
Degranulation
Production and release of inflammatory mediators
Enhancement of endothelial permeability
Upregulation of membrane adhesion molecules
Tissue Degradation:
Neutrophil entrapment in microvessels, transvascular migration
Platelet attachment, aggregation, thrombosis, red cell aggregation
Protease release and activation
Oxygen free radical formation
Apoptosis
Organ dysfunction
Initial Repair:
Downregulation of anti-inflammatory genes
Upregulation of pro-inflammatory genes (cytokines, etc.)
Monocyte and T-Lymphocyte infiltration
Repair:
Release of growth factors
Connective tissue growth
Revascularization
“Resolution of Inflammation”
Inflammation in the Microcirculation
Images removed due to copyright restrictions.
3
1
2
3
2
1
Figure by MIT OpenCourseWare.
Trigger Mechanisms for Cardiovascular Cell Activation
• Inflammatory mediators (bacterial/viral/fungal sources,
endotoxins, cytokines, histamine, oxidized
products, complement fragments, LTB4, PAF, etc.)
• Depletion of anti-inflammatory mediators (nitric oxide,
IL-10, glucocorticoids, albumin, etc.)
• Fluid stress
• Transients of Gas Pressure or Temperature
• Juxtacrine Activation
• Bio-Implant Interfaces
Plasma Derived Inflammatory Mediators in Hemorrhagic Shock
●
Leukotaxin Peptide
Nonsurvivors
Myocardial
Depressing Factor
❍ Survivors
Clastogenic factor
T-Lymphocyte proliferation depression factor
Neutrophil activating factor
No detectable bacterial or TNFα
activity
Leukocyte Chemotactic Factor
Neurin
Inflammatory Mediators in Hemorrhagic Shock 45
Plasma Exchange
NBT-Positive Neutrophil (%)
Nonsurvivors
Survivors
30
*
*
*
*
15
0
Control
0
40
100
160
220
280
Time (minutes)
Figure by MIT OpenCourseWare.