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Stress Repair Mechanism

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Based on Capillary Gate Theory and Tissue Repair Theory, this presentation will explain the recently identified “Stress Repair Mechanism” (SRM) that enables the long-anticipated Universal Theory of Medicine postulated by Hans Selye in 1954. The SRM maintains and repairs vertebrate tissues and accounts for most of the mysterious manifestations of allostasis that remain unexplained by Hypothalamic-Pituitary-Axis (HPA) hormones. SRM activity explains hemodynamic physiology, capillary hemostasis, infarction, Korotkoff sounds, blood pressure, hypertension, diabetes, allostasis, allostatic load, anesthesia, analgesia, atherosclerosis, apoptosis, malignancy, eclampsia, sepsis, Multi-System Organ Failure (MSOF), the surgical stress syndrome, the fight or flight response, and numerous other manifestations of physiology, pathology, and allostasis. SRM function comprises the autonomic nervous system, the vascular endothelium, and the dynamic enzymatic interaction of blood-borne hepatic Factors VII, VIIIC, IX and X that produces thrombin, soluble fibrin and insoluble fibrin, whose combined effects account for all SRM manifestations. The vascular endothelium is a diaphanous neuroendocrine organ that lines all blood vessels and is the sole constituent of capillary walls. It secretes tissue factor into extravascular tissues, and insulates those tissues from the hepatic enzymes, so that tissue disruption exposes tissue factor to the enzymatic interaction and activates tissue repair. The vascular endothelium also releases nitric oxide and von Willebrand Factor into blood in accord with autonomic balance to regulate the enzymatic interaction to govern tissue perfusion and organ function. Therefore, continuously fluctuating combinations of nervous stimuli that affect autonomic balance and forces that disrupt tissues determine SRM activity.

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Stress Repair Mechanism

  1. 1. Surgery Trauma Burns Sepsis Radiation Chemicals Toxins Stressful Forces Extravascular Tissue Disruption TISSUE REPAIR COMPONENT Tissue Factor Pathway Inhibitor ATIII Protein C Metabolism Angiogenesis Chemokines Cytokines Prostaglandins Malignancy Apoptosis Bone Muscle Pneumonia Influenza Asthma ARDS MSOF Eclampsia ARF Pus Scabs Casts Exudates Abscesses SOLUBLE FIBRIN TISSUE REPAIR Platelets Inflammation Chemotaxis Mitosis FIBRONIGEN Factor X Immune Proteins Temperature Catabolism Fever Immune Cells Endothelium Osteoblasts Myoblasts Fibroblasts Collagen Factor XIII Vitronectin Fibronectin COAGULATION SYSTOLIC TURBULENT RESISTANCE Hyperviscosity Hypercoagulable Flow Resistance Increased SWR Cardiac Work Hypertension Decreased CO Atherosclerosis Tissue Ischemia Hypoxemia Organ Quiescence Increased SWR Organ Stress Hypertension Decreased CO Increased HR Tissue Perfusion Hyperoxemia Organ Activity Decreased SVR Organ Preservation Hypotension Increased CO Decreased HR CAPILLARY HEMOSTASIS CAPILLARY FLOW SYSTOLIC LAMINAR FLOW Optimal Viscosity Normocoagulable Flow Facilitation Decreased SVR Cardiac Rest Hypertension Increased CO Health & Longevity Cerebral Cortex Fibrin Split Products Insoluble Fibrin TAFI THROMBIN TISSUE FACTOR Thrombin Activation Factor VII Krebs Cycle Ca+ Factor VIIIC Thrombin Acceleration VON WILLIBRAND FACTOR PAI TPA The Stress Repair Mechanism (SRM) Thrombin Amplification Factor IX VASCULAR ENDOTHELIUM Epinephrine Norepinephrine Cortisol HPA Axis Nitric Oxide Analgesia Visual, Olfactory Auditory, Tactile Pain CAPILLARY GATE COMPONENT Stressful Stimuli Intravascular Neurons Pathways ATP Nociception Internuncial Spinal Cord Hypothalamus Peripheral Nerves Peripheral Receptors Sensory Stressors SPINAL PATHWAY Emotional Mechanisms Anesthesia SYMPATHETIC PARASYMPATHETIC Insulin COGNITIVE PATHWAY Fibrosis Scar Adhesion The Universal Theory of Medicine of Hans Selye
  2. 2. Dr. Hans Selye 1907-1982
  3. 3. Capillary Gate Theory Tissue Repair Theory Coagulation Cascade Stress Repair Mechanism
  4. 4. Factor VIII: The Missing Link Von Willebrand’s Factor Vascular Endothelium Inert Fluctuates with Nervous activity Gigantic molecule Factor VIIIC liver Labile enzyme Generates Insoluble Fibrin Gigantic molecule
  5. 5. THROMBIN: THE UNIVERSAL ENZYME OF ENERGY TRANSDUCTION THROMBIN
  6. 6. Soluble Fibrin: The Universal Protein of Tissue Repair
  7. 7. Insoluble Fibrin: The Universal Polymer of Hemostasis
  8. 8. The Vascular Endothelium TF TF VWF SNS PNS NO TF
  9. 10. Vascular Endothelium Factor IX Stressful Forces Stressful Stimuli FactorVIII Factor VII Factor X Thrombin Soluble Fibrin Factor XIII Insoluble Fibrin Fibrinogen TAFI Cell Activity Capillary Gate Component Tissue Repair Component VWF TF
  10. 11. Capillary Gate Mechanism/Component <ul><li>Operates in flowing blood </li></ul><ul><li>Molecular level capillary gate that controls capillary flow </li></ul><ul><li>Closed by SNS release of VWF that generates Insoluble Fibrin that binds to red cells in capillary lumen </li></ul><ul><li>Opened by PNS release of NO that disintegrates Insoluble Fibrin into fibrin split products </li></ul><ul><li>Turbulence Mechanism regulates viscosity & coagulability in larger vessels </li></ul><ul><li>Controls blood pressure, heart rate, Cardiac Output, atherosclerosis </li></ul><ul><li>Controls organ function </li></ul><ul><li>Determines tissue perfusion and oxygenation </li></ul>
  11. 12. The Capillary Gate
  12. 13. Tissue Repair Mechanism/Component <ul><li>Clot formation (seals flowing blood from damaged tissues) </li></ul><ul><li>Inflammation (loosens cell connections) </li></ul><ul><li>Chemotaxis (attracts repair cells to damaged tissues) </li></ul><ul><li>Fibrin infiltration (forms structure for cell activity) </li></ul><ul><li>Cell proliferation & differentiation (replaces damaged tissues) </li></ul><ul><li>Production of collagen & bone </li></ul><ul><li>Angiogenesis (perfuses developing tissues) </li></ul><ul><li>Immune cell activity (removes debris & combats infection) </li></ul><ul><li>Apoptosis of repair cells (shrinks wound & enables closure) </li></ul>
  13. 14. Insoluble Fibrin The Coagulation Cascade
  14. 15. Burns Surgery Trauma Sepsis Radiation Chemicals Toxins Stressful Forces Extravascular Tissue Disruption TISSUE REPAIR COMPONENT Tissue Factor Pathway Inhibitor ATIII Protein C Metabolism Angiogenesis Chemokines Cytokines Prostaglandins Malignancy Apoptosis Bone Muscle Pneumonia Influenza Asthma ARDS MSOF Eclampsia ARF Pus Scabs Casts Exudates Abscesses SOLUBLE FIBRIN TISSUE REPAIR Platelets Inflammation Chemotaxis Mitosis FIBRONIGEN Factor X Immune Proteins Temperature Catabolism Fever Immune Cells Endothelium Osteoblasts Myoblasts Fibroblasts Collagen Factor XIII Vitronectin Fibronectin COAGULATION SYSTOLIC TURBULENT RESISTANCE Hyperviscosity Hypercoagulable Flow Resistance Increased SWR Cardiac Work Hypertension Decreased CO Atherosclerosis Tissue Ischemia Hypoxemia Organ Quiescence Increased SWR Organ Stress Hypertension Decreased CO Increased HR Tissue Perfusion Hyperoxemia Organ Activity Decreased SVR Organ Preservation Hypotension Increased CO Decreased HR CAPILLARY HEMOSTASIS CAPILLARY FLOW SYSTOLIC LAMINAR FLOW Optimal Viscosity Normocoagulable Flow Facilitation Decreased SVR Cardiac Rest Hypertension Increased CO Health & Longevity Cerebral Cortex Fibrin Split Products Insoluble Fibrin TAFI THROMBIN TISSUE FACTOR Thrombin Activation Factor VII Krebs Cycle Ca+ Factor VIIIC Thrombin Acceleration VON WILLIBRAND FACTOR PAI TPA The Stress Repair Mechanism (SRM) Thrombin Amplification Factor IX VASCULAR ENDOTHELIUM Epinephrine Norepinephrine Cortisol HPA Axis Nitric Oxide Analgesia Visual, Olfactory Auditory, Tactile Pain CAPILLARY GATE COMPONENT Stressful Stimuli Intravascular Neurons Pathways ATP Nociception Internuncial Spinal Cord Hypothalamus Peripheral Nerves Peripheral Receptors Sensory Stressors SPINAL PATHWAY Emotional Mechanisms Anesthesia SYMPATHETIC PARASYMPATHETIC Insulin COGNITIVE PATHWAY Fibrosis Scar Adhesion The Universal Theory of Medicine of Hans Selye
  15. 16. Charles Atlas or 90lb Weakling?
  16. 17. Blood Acceleration & Turbulence Systolic Acceleration Diastolic Deceleration Diastolic Turbulence
  17. 18. Pipe Flow Turbulence Lateral Forces Fast Faster Fastest
  18. 19. What Can It Do? <ul><li>Explains the manifestations of allostasis </li></ul><ul><li>Promises a rapid and reliable cure for cancer </li></ul><ul><li>Elimination of the Surgical Stress Syndrome </li></ul><ul><li>Advanced forms of invasive surgery </li></ul><ul><li>Fresh explanation of Rheumatoid Disease and effective treatments </li></ul><ul><li>Control of ARDS, MOFS, Eclampsia, Asthma, Pneumonia, Influenza, spinal cord shock, and sepsis </li></ul><ul><li>Control of plagues and epidemics </li></ul><ul><li>Fresh insights to embryology, evolution, parasitology, psychology </li></ul>
  19. 20. The End
  20. 21. New Research Information <ul><li>The Vascular Endothelium is a nervous gland that releases numerous hormones </li></ul><ul><li>The Vascular Endothelium releases VWF in accord with Sympathetic activity </li></ul><ul><li>Factor VIII consists of hepatic VIIIC plus VWF produced by the Vascular Endothelium </li></ul><ul><li>Thrombin energizes cell and enzyme activity </li></ul><ul><li>Thrombin requires both Ca+ and ATP </li></ul><ul><li>Agents that bind to Ca+ inhibit thrombin activity </li></ul><ul><li>The vascular endothelium releases Nitric Oxide in accord with Parasympathetic activity to induce “nitrergic neurogenic vasodilation” </li></ul><ul><li>All cells possess thrombin receptors in combinations that are characteristic of the cell type </li></ul><ul><li>Fibrinogen, soluble fibrin and insoluble fibrin can now be distinguished </li></ul>
  21. 24. Fostering communication Physicians  Medical Research  Teams Practice Theory Intra domain specialization Inter domain communication Inter domain communication

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