Upload
lorant
View
44
Download
0
Tags:
Embed Size (px)
DESCRIPTION
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 - PowerPoint PPT Presentation
Citation preview
Effects of AcuteBP Elevation onthe Vessel Wall
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
Pathophysiology of hypertension
INAPPROPRIATELY HIGH SYMPATHETIC OUTFLOW
Increased large arterial stiffness
Inappropriately high
cardiac output
Abnormal venoconstriction
and high venous return
INAPPROPRIATELY HIGH RENIN RELEASE
ABNORMAL RENAL
SALT/WATER HANDLING
Increased systemic
resistance
Courtesy of JL Izzo Jr, MD.
NO
PGI2
CatecholaminesAT-II
ADH (vasopressin)Aldosterone
TxA2
ET1
Endogenous vasoconstrictors
The endothelium modulates vascular tone
Courtesy of JJ Ferguson III, MD.
Endogenous vasodilators
Proposed vascular pathophysiology of hypertensive urgency
Vaughan CJ, Delanty N. Lancet. 2000;356:411-7.Courtesy of JJ Ferguson III, MD.
Acute ↑ BP triggers ↑ cellular adhesion molecular expression
NO
PGI2
CatecholaminesAT-II
ADH (vasopressin)Aldosterone
TxA2
ET1( - ) ( + )
CAMs
Endogenous vasodilators
Endogenous vasoconstrictors
• Overwhelmed control of vascular tone leads to coagulation cascade activation• Loss of endothelial activity coupled with coagulation and platelets promotes DIC
Proposed vascular pathophysiology of hypertensive emergency
Vaughan CJ, Delanty N. Lancet. 2000;356:411-7. Courtesy of JJ Ferguson III, MD.
TxA2
Endothelial shear stress
Chatzizisis YS et al. J Am Coll Cardiol. 2007;49:2379-93.ESS = endothelial shear stress
Proportional to the product of blood viscosity (μ) and spatial gradient of
blood velocity at the wall (dv/dy).
Endothelial mechanoreceptors sense changes in shear stress
Chatzizisis YS et al. J Am Coll Cardiol. 2007;49:2379-93.ESS = endothelial shear stress
Shear stress rapidly activates endothelial signal transduction and gene expression
Chien S et al. Hypertension. 1998;31[part 2]:162-9.
Maximum activation
Signal Transduction
Basal activityRas
ERKJNK
0 30 60min
Ac
tiv
ati
on
Maximum activation
Gene Expression
Basal activity
C-fos mRNAMCP-1 mRNA
0 60 120min
Ac
tiv
ati
on
180 240
Definition and example of pulsatile, low, and oscillatory ESS
Chatzizisis YS et al. J Am Coll Cardiol. 2007;49:2379-93.ESS = endothelial shear stress
Cross-section
Bloodflow
Pulsatile ESS(15-70 dyne/cm2)- Direction: Unidirectional- Magnitude: Physiologic time-average
Low and oscillatory ESS(<10-12 dyne/cm2)- Direction: Bidirectional (oscillatory)- Magnitude: Low time-average
Chatzizisis YS et al. J Am Coll Cardiol. 2007;49:2379-93.
Implications of low and high shear stress
Effects of high shear stress
Endothelial dysfunction
Vascular injury
Thrombosis
Neurohumoral activation
Atherosclerosis
Plaque rupture
Effects of low shear stress
Perioperative triggers of adverse physiologic states
• Surgical trauma
• Anesthesia/analgesia
• Intubation/extubation
• Pain
• Hypothermia
• Bleeding/anemia
• Fasting
• Transfusion
Devereaux PJ et al. CMAJ. 2005;173:627-34.
Inflammatory
Hypercoagulable
Stress
Hypoxia
Physiologic state
Proposed mechanisms of perioperative MI
Devereaux PJ et al. CMAJ. 2005;173:627-34.
InflammationHypercoagulable
stateStress Hypoxia
↑TNF-α↑IL-1↑IL-6↑CRP
↑PAI-1↑Factor VIII↑Platelet reactivity↑Antithrombin III
↑Catecholamine and cortisol levels
↓Oxygen delivery
Plaque fissuring
Coronary artery shear stress
Plaque fissuring
↑BP↑HR↑FFAs↑Relative insulin
deficiency
↑Oxygen demand
Myocardial ischemia
Acute coronary thrombosis
Perioperative myocardial infarction
Summary: The pathophysiology of acute hypertensive syndromes
Mechanical stress on the vessel wall
↑BPRelease of humoral
vasoconstrictors
↑BP
Endothelial damage
Activation of the clotting cascade
Further release of humoral
vasoconstrictors
Fibrinoid necrosis of small blood
vessels
Pressure natriuresis
Volume depletion
RAAS activation
Vasopressinendothelin
catecholaminesMajor physiologic
derangements Courtesy of JJ Ferguson III, MD.
Pathophysiology of acute hypertensive syndromes: A vicious cycle
Courtesy of JJ Ferguson III, MD.
Vascular injury
Tissue ischemia
Vasoconstrictor release
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
Acute hypertension: Conclusions
• New options are needed
• Need for long-term patient follow-up in hypertensive urgencies/emergencies