1 / 17

Effects of Acute BP Elevation on the Vessel Wall

Effects of Acute BP Elevation on the Vessel Wall. Pathophysiology overview. Sustained neurohormonal activation and vasoconstriction leads to Endothelial decompensation Altered vascular structure. Vicious cycle of homeostatic failure begins, leading to

lorant
Download Presentation

Effects of Acute BP Elevation on the Vessel Wall

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Effects of AcuteBP Elevation onthe Vessel Wall

  2. Pathophysiology overview • Sustained neurohormonal activation and vasoconstriction leads to • Endothelial decompensation • Altered vascular structure • Vicious cycle of homeostatic failure begins, leading to • Loss of cerebral and local autoregulation • Organ system ischemia and dysfunction • Myocardial infarction

  3. Pathophysiology of hypertension INAPPROPRIATELY HIGH SYMPATHETIC OUTFLOW Increased large arterial stiffness Abnormal venoconstriction and high venous return Increased systemic resistance Inappropriately high cardiac output INAPPROPRIATELY HIGH RENIN RELEASE ABNORMAL RENAL SALT/WATER HANDLING Courtesy of JL Izzo Jr, MD.

  4. The endothelium modulates vascular tone Catecholamines NO AT-II TxA2 Endogenous vasoconstrictors Endogenous vasodilators ET1 PGI2 Aldosterone ADH (vasopressin) Courtesy of JJ Ferguson III, MD.

  5. Proposed vascular pathophysiology of hypertensive urgency CAMs Catecholamines AT-II NO Endogenous vasoconstrictors TxA2 Endogenous vasodilators ( - ) ( + ) ET1 PGI2 Aldosterone ADH (vasopressin) Acute ↑ BP triggers ↑cellular adhesion molecular expression Vaughan CJ, Delanty N. Lancet. 2000;356:411-7.Courtesy of JJ Ferguson III, MD.

  6. Proposed vascular pathophysiology of hypertensive emergency TxA2 • Overwhelmed control of vascular tone leads to coagulation cascade activation • Loss of endothelial activity coupled with coagulation and platelets promotes DIC Vaughan CJ, Delanty N. Lancet. 2000;356:411-7. Courtesy of JJ Ferguson III, MD.

  7. Endothelial shear stress Proportional to the product of blood viscosity (μ) and spatial gradient of blood velocity at the wall (dv/dy). ESS = endothelial shear stress Chatzizisis YS et al. J Am Coll Cardiol. 2007;49:2379-93.

  8. Endothelial mechanoreceptors sense changes in shear stress ESS = endothelial shear stress Chatzizisis YS et al. J Am Coll Cardiol. 2007;49:2379-93.

  9. Shear stress rapidly activates endothelial signal transduction and gene expression Signal Transduction Gene Expression Maximum activation Maximum activation Activation Activation Basal activity Basal activity Ras ERK MCP-1 mRNA JNK C-fos mRNA min min 0 30 60 0 60 120 180 240 Chien S et al. Hypertension. 1998;31[part 2]:162-9.

  10. Definition and example of pulsatile, low, and oscillatory ESS Low and oscillatory ESS(<10-12 dyne/cm2) - Direction: Bidirectional (oscillatory) - Magnitude: Low time-average Pulsatile ESS(15-70 dyne/cm2) - Direction: Unidirectional - Magnitude: Physiologic time-average Cross-section Bloodflow ESS = endothelial shear stress Chatzizisis YS et al. J Am Coll Cardiol. 2007;49:2379-93.

  11. Implications of low and high shear stress Effects of low shear stress Effects of high shear stress Endothelial dysfunction Vascular injury Thrombosis Neurohumoral activation Atherosclerosis Plaque rupture Chatzizisis YS et al. J Am Coll Cardiol. 2007;49:2379-93.

  12. Perioperative triggers of adverse physiologic states • Surgical trauma • Anesthesia/analgesia • Intubation/extubation • Pain • Hypothermia • Bleeding/anemia • Fasting • Transfusion Physiologic state Inflammatory Hypercoagulable Stress Hypoxia Devereaux PJ et al. CMAJ. 2005;173:627-34.

  13. Proposed mechanisms of perioperative MI Inflammation Hypercoagulablestate Stress Hypoxia ↑TNF-α ↑IL-1 ↑IL-6 ↑CRP ↑PAI-1 ↑Factor VIII ↑Platelet reactivity ↑Antithrombin III ↑Catecholamine and cortisol levels ↓Oxygen delivery Coronary artery shear stress ↑BP ↑HR ↑FFAs ↑Relative insulin deficiency Plaque fissuring Plaque fissuring ↑Oxygen demand Acute coronary thrombosis Myocardial ischemia Perioperative myocardial infarction Devereaux PJ et al. CMAJ. 2005;173:627-34.

  14. Major physiologic derangements Summary: The pathophysiology of acute hypertensive syndromes Mechanical stress on the vessel wall Release of humoral vasoconstrictors ↑BP ↑BP Further release of humoral vasoconstrictors Pressure natriuresis Volume depletion Fibrinoid necrosis of small blood vessels Endothelial damage Vasopressin endothelin catecholamines RAAS activation Activation of the clotting cascade Courtesy of JJ Ferguson III, MD.

  15. Pathophysiology of acute hypertensive syndromes: A vicious cycle Vasoconstrictor release Tissue ischemia Vascular injury Courtesy of JJ Ferguson III, MD.

  16. Summary: Acute hypertension Nonsurgical patients • Little studied in past decade • Multiple knowledge gaps • Patient characteristics • Treatment patterns • Outcomes Perioperative patients • Frequent finding • Emerging data demonstrate importance of tighter BP control than currently recommended

  17. Acute hypertension: Conclusions • New options are needed • Need for long-term patient follow-up in hypertensive urgencies/emergencies

More Related