Treatment-Resistant Hypertension:
This presentation is the property of its rightful owner.
Sponsored Links
1 / 12

Treatment-Resistant Hypertension: Pathophysiology PowerPoint PPT Presentation


  • 143 Views
  • Uploaded on
  • Presentation posted in: General

Treatment-Resistant Hypertension: Pathophysiology. Power Over Pressure www.poweroverpressure.com. Perceptions of hypertension have changed over time. High BP Is Bad!. High BP Is Good!.

Download Presentation

Treatment-Resistant Hypertension: Pathophysiology

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.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Treatment resistant hypertension pathophysiology

Treatment-Resistant Hypertension:

Pathophysiology

Power Over Pressure

www.poweroverpressure.com


Perceptions of hypertension have changed over time

Perceptions of hypertension have changed over time

High BP Is Bad!

High BP Is Good!

  • Landmark study demonstrated a 96% reduction in CV events over 18 months with the use of a triple antihypertensive regimen compared with placebo in patients with severe hypertension (P<0.001).3,4

  • Arterial pressure is elevated to overcome mechanical resistance against blood flow in renal disease.1 (Traube)

  • (Theory generalized to include hypertension due to various etiologies).1

  • Efficiency of the kidney is not altered by marked fall in BP, occurring spontaneously or induced.1(Page)

  • In patients with chronic kidney disease, a fall in BP occurring spontaneously or as a result of surgical renal denervation caused no change in renal efficiency.1

  • The widespread opinion in the 1950s was that lowering BP could be harmful.2

  • Lowering BP would impair perfusion of vital organs, increasing CV risk and renal disease.2

Low BP Is Bad!

Is High BP Good?

BP = blood pressure; CV = cardiovascular.

1. Page IH. J Clin Invest. 1934;13:909-915. 2. Chobanian AV. N Engl J Med. 2009;361:878-887. 3. Veterans AdministrationCooperative Study Group. JAMA. 1967;202:1028-1034. 4. Calhoun DA, et al. Circulation. 2008;117(25):e510-e526.

Power Over Pressure

www.poweroverpressure.com


The kidney is a central regulator of the electrical chemical and mechanical forces that control bp

The kidney is a central regulator of the electrical, chemical, and mechanical, forces that control BP

SNS

Electrical

Brain

RAAS

Kidney: BP Regulation

Cytokines

Chemical

Neurohormones

Heart rate

Vasodilation/

Vasoconstriction

Mechanical

Volume control

SNS = sympathetic nervous system.

RAAS = renin-angiotensin-aldosterone/system.

Campbell W. The Autonomic and Peripheral Nervous Systems. In: Campbell, WW, editor. DeJong's The Neurologic Examination. 6th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2005 p. 535-547. Cowley A. Nat Rev Genetics. 2006;7:829-840. Kaplan NM, Victor R. Kaplan's Clinical Hypertension. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2010. Schlaich M, et al. Hypertension. 2009;54:1195-1201. Guyton AC. Science. 1991;252:1813-1816.

Power Over Pressure

www.poweroverpressure.com


Primary electrical component of bp control is the sympathetic nervous system sns

Primary electrical component of BP control is the sympathetic nervous system (SNS)

  • The SNS is part of the body’s autonomic nervous system

    • Operates without conscious control

  • The SNS connects the brain, heart, blood vessels, and kidneys, each of which plays an important role in the regulation of BP

Dilates pupils

Inhibits salivation

Cervical

Relaxes bronchi

Accelerates heart

Thoracic

Inhibits digestive activity

Stimulates glucose release by liver

Lumbar

Epinephrine—adrenal glandsNorepinephrine—kidney

Relaxes bladder

Contracts rectum

Campbell W. The Autonomic and Peripheral Nervous Systems. In: Campbell, WW, editor. DeJong's The Neurologic Examination.6th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2005 p. 535-547.

Power Over Pressure

www.poweroverpressure.com


Treatment resistant hypertension pathophysiology

The kidneys are the most central contributors to BP, playing electrical, mechanical, and hormonal roles

 Neurohormones

 Blood Pressure

 Vasoconstriction

 Contractility/Rate

 RBF/GFR

 Na+/Volume

 Renin

Ang II

Ang II = Angiotensin II.

Aldo = Aldosterone.

RBF = Renal blood flow.

GFR = Glomerular filtration rate.

Adapted from Schlaich MP, et al. Hypertension. 2009;54:1195-1201.Hall JE, Guyton AC. Textbook of Medical Physiology. 12th ed. Philadelphia, PA: Saunders Elsevier, 2011.

Aldo

Power Over Pressure

www.poweroverpressure.com


Kidneys are the most central contributors to bp playing electrical mechanical and hormonal roles

Kidneys are the most central contributors to BP, playing electrical, mechanical, and hormonal roles

 Neurohormones

 Blood Pressure

 Vasoconstriction

 Contractility/Rate

Kidney impairment or dysfunction =  afferent activity

 RBF/GFR

 Na+/Volume

 Renin

Ang II

Aldo

Adapted from Schlaich MP, et al. Hypertension. 2009;54:1195-1201.Hall JE, Guyton AC. Textbook of Medical Physiology. 12th ed. Philadelphia, PA: Saunders Elsevier, 2011.

Power Over Pressure

www.poweroverpressure.com


Kidneys are the most central contributors to bp playing electrical mechanical and hormonal roles1

Kidneys are the most central contributors to BP, playing electrical, mechanical, and hormonal roles

 Neurohormones

 Blood Pressure

 Vasoconstriction

 Contractility/Rate

Kidney impairment or dysfunction =  afferent activity

Amplifies central, or systemic, sympathetic outflow

 RBF/GFR

 Na+/Volume

 Renin

Ang II

Aldo

Adapted from Schlaich MP, et al. Hypertension. 2009;54:1195-1201.Hall JE, Guyton AC. Textbook of Medical Physiology. 12th ed. Philadelphia, PA: Saunders Elsevier, 2011.

Power Over Pressure

www.poweroverpressure.com


Kidneys are the most central contributors to bp playing electrical mechanical and hormonal roles2

Kidneys are the most central contributors to BP, playing electrical, mechanical, and hormonal roles

 Neurohormones

 Blood Pressure

 Vasoconstriction

 Contractility/Rate

Kidney impairment or dysfunction =  afferent activity

Amplifies central, or systemic, sympathetic outflow

 RBF/GFR

 Na+/Volume

 Renin

Ang II

Aldo

Adapted from Schlaich MP, et al. Hypertension. 2009;54:1195-1201.Hall JE, Guyton AC. Textbook of Medical Physiology. 12th ed. Philadelphia, PA: Saunders Elsevier, 2011.

Power Over Pressure

www.poweroverpressure.com


Renin angiotensin aldosterone s ystem raas is central to the pathogenesis of hypertension

Renin-angiotensin-aldosterone system (RAAS) is central to the pathogenesis of hypertension

Increased sympathetic activity

Tubular Na+ reabsorption, K+ excretion and water retention

Water and salt retention. Effective circulating volume increases. Perfusion of the juxtaglomerular apparatus increases

Pulmonary and renal epithelium:

ACE

Aldosterone secretion

Angiotensinogen

Angiotensin I

Angiotensin II

Renin

Vasoconstriction and increased BP

Decrease in renal perfusion

Antidiuretic hormone secreted from pituitary, leading to water absorption

Power Over Pressure

www.poweroverpressure.com

Schrier RW, ed. Renal and Electrolyte Disorders 5th ed.1997.


Sympathetic drive plays a critical role in hypertension

Sympathetic drive plays a critical role in hypertension

Efferent Renal Sympathetics

Afferent Renal Sympathetics

Sympathetic signals from the CNS modulate the physiology of the kidneys

The kidney is a source of central sympathetic activity, sending signals to the CNS

CNS = central nervous system.

Adapted from Schlaich MP, et al. Hypertension. 2009;54:1195-1201.

Power Over Pressure

www.poweroverpressure.com


Sympathetic drive is elevated in multiple types of hypertension

Sympathetic drive is elevated in multiple types of hypertension

80

Single-unit efferent sympathetic nerve activity (s-MSNA)

†‡§#

†‡§

60

*द

*†

*

Sympathetic Activity per Minute

40

*†

Baseline activity (normotensives)

20

0

White-coat

High Normals

Normotensives

Borderline Hypertension

Essential Hypertension With LVH

Essential Hypertension – Stage 1

Essential Hypertension – Stages 2 and 3

LVH=left ventricular hypertrophy.

*P<0.05 Compared with borderline hypertension. / †P<0.05 Compared with white-coat hypertension. / ‡P<0.05 Compared with normal pressure.

§P<0.05 Compared with high-normal pressure. / ¶P<0.05 Compared with essential hypertension–stage 1. / #P<0.05 Compared with essential hypertension–stages 2 and 3.

Adapted from Smith P, et al. Am J Hypertens.2004; 217-222.

Power Over Pressure

www.poweroverpressure.com


Summary pathophysiology of treatment resistant hypertension

Summary: pathophysiology of treatment-resistant hypertension

  • While treatment-resistant hypertension is a well-recognized phenomenon, perceptions of hypertension have changed over time

  • BP is controlled by the complex interaction of several forces

    • Electrical: SNS, brain

    • Hormonal: RAAS, cytokines, neurohormones

    • Mechanical: heart rate, vasodilation/vasoconstriction, volume control

  • The kidneys play a major role in BP control due to their intrinsic SNS connection

  • Salt and water homeostasis along with BP regulation are controlled by RAAS

  • Efferent and afferent signaling between the CNS and kidneys play a critical role in hypertension

  • Elevated SNS activity is found in patients with multiple types of hypertension

Power Over Pressure

www.poweroverpressure.com


  • Login