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THE AUSTRALIAN NATIONAL UNIVERSITY. Neural Regulation of Blood Pressure Christian Stricker Associate Professor for Systems Physiology ANUMS/JCSMR - ANU Christian.Stricker@anu.edu.au http:/ /stricker.jcsmr.anu.edu.au/BPControl.pptx. Aims. The students should

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THE AUSTRALIAN NATIONAL UNIVERSITY

Neural Regulation ofBlood PressureChristian StrickerAssociate Professor for Systems PhysiologyANUMS/JCSMR - ANUChristian.Stricker@anu.edu.auhttp://stricker.jcsmr.anu.edu.au/BPControl.pptx

slide3
Aims

The students should

  • know the sensors, integrators and effectors of the regulating reflexes;
  • be cognisant of the anatomy of the reflex pathways;
  • understand which and how the three system parameters HR, SV and TPR are regulated;
  • be able to explain the nature and effect of the arterial baroreflex (AB) and the cardiopulmonary reflexes (CP);
  • realise that AB controls HR, SV and TPR, and CP mainly venous return;
  • know how AB establishes beat-to-beat control; and
  • appreciate how these reflexes can be modulated by respiration and asphyxia/shock.
contents
Contents
  • Overview of control of blood pressure
    • Principles of negative feedback
    • Regulated variables
  • Arterial baroreflex (AB)
    • Components: detectors (high pressure baroreceptors) and afferents, efferents (sympathetic and parasympathetic output to cardiovascular system), integrator.
  • Cardiopulmonary reflexes (CP)
    • Low pressure baroreceptors
    • Atrial stretch and release of ANP
  • Respiratory and chemoreflex modulation of baroreflex activity.
topic coverage
Topic Coverage
  • In this session, we ONLY look at BP control on the short-term (seconds).
  • Long-term BP control via volume control will be done in relation to kidney (see later “Volume regulation”).
  • How vessels locally regulate resistance will be subject of the next lecture.
overview of bp control
Overview of BP Control
  • In Block 1, mean arterial pressure was defined as is mean arterial pressure (MAP), TPR total peripheral resistance, CO cardiac output, SV stroke volume and HR heart rate.
  • controlled by 3 variables: TPR, SV and HR.
  • Which system can control these parameters?
    • Autonomic nervous system:
      • HR: sympathetic (+), parasympathetic (-; vagal) at level of heart
      • SV: sympathetic (+), parasympathetic (-) at level of heart; sympathetic (+) at the level of TPR (afterload); and others.
      • TPR: sympathetic (+) ONLY at level of vessels (and other factors like volume, etc.).
principles of feedback control
Principles of Feedback Control
  • Positive and negative feedback.
  • Feed-forward: central command before exercise starts.
  • Functional characteristic is feedback time: from few 100 ms to hours or even longer.
overview of reflex control
Overview of Reflex Control

Levick, 5th ed., 2010

  • Two reflexes involved:
    • arterial baroreflex (AB) and
    • cardio-pulmonary reflexes (CP).
      • Modulated by respiration, chemoreceptors and muscle activity.
arterial baroreceptor reflex ab

Arterial Baroreceptor Reflex (AB)

Mostly negative feedback to brainstem, sympathetic nervous system and heart: Depressor reflex.

If BP↑ → HR↓, SV↓, TPR↓ and vice versa if BP↓.

Most important contributor to short-term homeostatic control of BP (s - min).

locations of ab sensors
Locations of AB Sensors

Levick, 5th ed., 2010

  • Pressoreceptors in aortic arch and carotid sinus.
  • Afferent nerves: IX (carotid sinus) & X (aortic arch).
ab sensor properties
AB Sensor Properties

Modified from Levick, 5th ed., 2011

  • True mechanoreceptors (wall tension in vessel).
  • Sensitive over large BP range
    • Low pressure range: A-fibres; high pressure range: C-fibres.
    • Linear response in “normal” range.
    • Respond better to pulsatile than steady pressure: adaptation under steady (static) conditions, much less under pulsatile (dynamic): poor at relaying absolute BP information.
ab set point and sensitivity
AB Set-Point and Sensitivity
  • Set-point = maximal slope in HR vs BP plot.
  • Maximal sensitivity 80 – 100 torr.
  • Exercise resets set-point: work in higher range without incurring depressor response; i.e. at same BP, a higher HR can be achieved.
    • Reset in proportion to work intensity.
    • AB active but HR is per-mitted to increase (muscle spindles).

Levy, 5th ed., 2010

ab efferent activity
AB Efferent Activity
  • SY output over whole sympathetic chain (T1 – L3).
  • Parasympathetic output via VA and lumbosacral cord (S2 – S4).
  • Both systems are activated wholly.
  • VA and SY outputs act together but in opposite directions:
    • VA↓ → SY↑ or
    • VA↑ → SY↓.
  • For > 180 torr, VA is maximised and SY minimised.

Kollai & Koizumi, Pflügers Arch (1989), 413:365-371

central ab pathways
Central AB Pathways

Levick, 5th ed., 2010

  • Control area in brainstem (several nuclei) receives input from / sends outputs to many brain parts (hypothalamus).
  • VA relay simpler (NTS → NA) than that of SY pathway.
medullar interactions
Medullar Interactions

Levick, 5th ed., 2010

  • VA→ SY inhibition (dashed lines) via
    • caudal inhibiting rostral vasopressor area (via GABA) and
    • raphe nucleus to spinal cord (via serotonin).
ab function
AB Function
  • AB helps to stabilise BP control beat by beat (fast response) within narrow range – if taken away, BP fluctuates widely.
  • Effect via VA↑ and SY↓ activity when BP↑: HR↓, SV↓ and TPR↓ and vice versa.
  • VA and SY work together in opposite direction.
  • During exercise, set-point shifted such that BP can rise without HRinhibition.
  • Can be modulated via inputs from respiratory and other centres.
  • Activated in orthostasis, dehydration, blood loss, shock, etc.
cardiopulmonary reflexes cp

Cardiopulmonary Reflexes (CP)

Collection of various reflexes based on sensor types.

Low-pressure receptor reflexes.

Most afferent input is also inhibitory.

Work predominantly on VR

cardiopulmonary reflexes cp1
Cardiopulmonary Reflexes (CP)
  • Cardiac de-afferentiation (transplant) reveals tonic inhibition of HR and TPR only.
    • Intracoronary injection of solute causes bradycardia, vasodilation and hypotension:
      • Depressor reflex
  • Important to know some specific reflexes as some can cause only SY↑ activity:
    • Activation of veno-atrial stretch receptors causes tachycardia and diuresis.
locations types of cp sensors
Locations & Types of CP Sensors

Levick, 5th ed., 2010

  • Mostly small, unmyelinated (80%) fibres from
    • cardiac mechano-receptors (wall tension in ventricle);
    • ventricular chemosensors (mediate pain via SY fibres): SY activity↑;
    • coronary artery baroreceptors (perfusion pressure); and
  • Some myelinated (20%): veno-atrial mechanoreceptors.
2 veno atrial stretch receptors
2. Veno-Atrial Stretch Receptors
  • Measure atrial blood volume, i.e. central venous pressure/volume in low pressure part of circulation (central veins, atria); control venous return (VR).
  • Upon activation (via infusion - ‘Bainbridge effect’)
    • tachycardia: SY activity↑ to SA node without change inVA activity; and
    • diuresis and natriuresis: control of blood volume via renal vasodilation (renal Na+ excretion↑), anti-diuretic hormone release↓ (hypothalamus) and release↑ of atrial natriuretic peptide (ANP) by atrial cells.
  • Part of long-term volume regulation response (see volume control in kidney section, later).
respiratory modulation
Respiratory Modulation
  • During inspiration, HR↑:
    • Inspiratory centre inhibits vagal output (motoneurones shortly unresponsive to AB input) → disinhibition of SA node → HR↑.
  • Converse is true during expiration.
  • Emotional faint: VA output↑ → HR↓↓.

Levick, 5th ed., 2010

arterial chemoreceptors
Arterial Chemoreceptors (+)
  • Carotid and aortic bodies (see respiration, later): sense and .
  • If < 80 torr (asphyxia, clinical shock, …):
    • TPR↑ as renal, splanchnic and muscle vascular beds are constricted;
    • Splanchnic veins constrict → pooling↓ → PMSF↑ → SV↑ → CO↑.
    • BP↑ as TPR↑ and CO↑.
    • Tachycardia due to resp. rate ↑ (lung stretch receptors inhibit VA output).
take home messages
Take-Home Messages
  • Under resting conditions, VA output on heart is more effective than that of SY.
  • Both, VA and SY nerves are tonically active and oppose each other; VA effect is fast, SY effect appreciably slower.
  • AB provides important short-term regulation of BP:
    • If BP↑, high pressure receptors in aortic arch and carotid sinus cause HR↓, SV↓ and TPR↓ and vice versa.
  • Cardiac de-afferentiation reveals tonic inhibitory effect on HR and TPR – part of CP reflexes.
  • Veno-atrial stretch receptors help control BP↑ mainly via circulating blood volume↓ / VR↓; i.e. renal vasodilation, hypothalamic release↓ of ADH and atrial release↑ of ANP.
  • When BP falls < 80 torr, peripheral chemoreceptors modulate BP via vasoconstriction plus tachycardia.
slide25
MCQ

Jack West, a 28 year-old bike rider was involved in a car accident on the road to the snowfields. He suffered a broken femur and was immediately transferred to Cooma Base Hospital. On admission, his HR was 112 bpm, and his blood pressure 65 / 45 torr. Which of the following statements best describes the state of the arterial baro- and cardiopulmonary reflex?

  • Arterial baroreceptor activity↓; sympathetic outflow↓; parasympathetic outflow↑; low pressure mechanoreceptor activity↓.
  • Arterial baroreceptor activity↑; sympathetic outflow↑; parasympathetic outflow↓; low pressure mechanoreceptor activity↓.
  • Arterial baroreceptor activity↓; sympathetic outflow↑; parasympathetic outflow↓; low pressure mechanoreceptor activity↓.
  • Arterial baroreceptor activity↑; sympathetic outflow↓; parasympathetic outflow↑; low pressure mechanoreceptor activity↑.
  • Arterial baroreceptor activity↑; sympathetic outflow↑; parasympathetic outflow↓; low pressure mechanoreceptor activity↑.
slide27
MCQ

Jack West, a 28 year-old bike rider was involved in a car accident on the road to the snowfields. He suffered a broken femur and was immediately transferred to Cooma Base Hospital. On admission, his HR was 112 bpm, and his blood pressure 65 / 45 torr. Which of the following statements best describes the state of the arterial baro- and cardiopulmonary reflex?

  • Arterial baroreceptor activity↓; sympathetic outflow↓; parasympathetic outflow↑; low pressure mechanoreceptor activity↓.
  • Arterial baroreceptor activity↑; sympathetic outflow↑; parasympathetic outflow↓; low pressure mechanoreceptor activity↓.
  • Arterial baroreceptor activity↓; sympathetic outflow↑; parasympathetic outflow↓; low pressure mechanoreceptor activity↓.
  • Arterial baroreceptor activity↑; sympathetic outflow↓; parasympathetic outflow↑; low pressure mechanoreceptor activity↑.
  • Arterial baroreceptor activity↑; sympathetic outflow↑; parasympathetic outflow↓; low pressure mechanoreceptor activity↑.