Cardiovascular Regulation, Physiology

1. D R . V . S I N G H C H A U H A N
( O R T H O . S U R G E R Y )
F A C I L I T A T O R : D R . M F D I N
Cardiovascular Regulation
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

2. At a Glance
 Need for CVS Control
 Role of Kidney in regulation (Done earlier)
 Control Systems
1. Humoral
a. Vasodilators
b. Vasoconstrictors
c. Ions
2. Neuronal
3. Local
a. Acute
b. Long Term
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

3. Need for Control
 To increase blood supply to active tissues
 Exercise
 Redistribution of blood
 To increase/decrease heat loss from body as per req.
 Circulatory adjustments
 During routine CVS stresses e.g change in posture, meals, sleep
 Maintenance of adequate flow to vital organs
 Brain, Kidneys, Heart at all times
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

4. Circulatory Adjustments
 Control of Blood Volume
 Control of Arterial Pressure
BP
CO TPR
SV HR
EDV ESVDistensibility
Filling Time Filling Pressure Contractility
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

5. What is regulated
 Cardiac Performance
 Alterations in activity of heart
 Chronotrophic Action
o Effect on HR
 Ionotrophic Action
o Effect on force of contraction
 Dromotrophic Action
o Effect on conduction of impulses through the heart
 Bathmotrophic Action
o Effect on excitability of cardiac muscle
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

6. What is Regulated
 Blood Vessel Performance
 Alterations in diameter of arterioles
 Change in PR and also hydrostatic pressure in capillaries
 Alterations in diameter of veins
 Change in venous pressures…..change in Venous return & CO
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

7. Cardiovascular Regulation
Humoral
 Neural
 Local
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

8. Humoral Control
 Important Factors
 Circulatory Vasodilators
 Kinins
 ANP (Atrial Natriuretic Peptide)
 Circulatory Vasoconstrictors
 Catecholamines
 Angiotensin II
 Vasopressin
 Ions and other chemical factors
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

9. Circulatory Vasodilators
1. Kinin
• Peptides
• Include
 Bradykinin
 Lysyl- Bradykinin
• Functions
 Vasodilation
 Relax Vascular SM via NO & increase capillary
permeability
 Role in regulating blood flow esp to skin, salivary glands &
GIT glands
 May play a role in thermoregulatory vascular
adjustments.
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

10. Circulatory Vasodilators
 ANP
 Secreted by heart and antagonises the actions of various
vasoconstrictors hence lowers BP
 Exact role not known but,
 Kidney
 Increases Sodium ion excretion
 Increases capillary permeability…extravasation….decreased BP
 Relaxes vascular SM in arterioles and venules
 Inhibit Renin secretion & counteract pressor effect of
Catecholamines and Angiotensin 1
 Brain
 Effects opposite to that of Angiotensin 1….Lowers BP, promotes
Natriuresis
 Found in areas concerned with neural regulation of CVS
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

11. Circulatory Vasoconstrictors
 Catecholamines
 Released on sympathetic stimulation
 Include
 Epinephrine
 Norepinephrine
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

12. Circulatory Vasoconstrictors
 Epinephrine
 Stimulate both alpha & beta adrenergic receptors
 Alpha – Vasoconstriction in skin & Splanchnic areas
 Beta – Dilatation of vessels in skeletal muscles, Liver &
coronary arteries.
 Beta receptor induced vasodilation is more dominant than
alpha receptor induced vasoconstriction.
 Net effect – Slight lowering of PR….decrease in DBP
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

13. Circulatory Vasoconstrictors
 Norepinephrine
 Generalised vasoconstrictor effect….alpha>beta
 Increases PR & raises DBP
 Direct cardiac stimulation has negligible effect since it has
negligible effect on beta receptors
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

14. Humoral Control
 Important Factors
 Circulatory Vasodilators
 Kinins
 ANP (Atrial Natriuretic Peptide)
 Circulatory Vasoconstrictors
 Catecholamines
Angiotensin II
 Vasopressin
 Ions and other chemical factors
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

15. Renin Angiotensin System
 Renin
 Secreted by JG Apparatus cells of Kidney into blood
 Secretion stimulated by fall in BP
Angiotensinogen Angiotensin 1 Angiotensin 2
 Effects of Angiotensin II
 Vasoconstriction
 4-8 times more potent than norepinephrine
 Decrease in salt & water excretion by kidneys…..retention of salt and
water……increase in ECF vol…..increase in arterial pressure over
period of hours and days.
 Long term control of arterial pressure
Renin ACE
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

16.  Effect of Angiotensin II
 Stimulation of thirst
 Leads to increased consumption of water hence increased blood
volume
 Long term control of BP
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

17. Vasopressin
 A.k.a Anti Diuretic Hormone
 Mainly affects water reabsorption in renal tubules
 Production –
 Concentration rises to high levels after severe
haemorrhage after which it starts having a
vasocontrictive effect.
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

18. Ions and other chemical factors
 Alter local blood flow
 Calcium – Vasoconstriction
 Potassium – Vasodilation
 Hydrogen ion – Vasodilation
 CO2 – Vasodilation in most tissues, marked in brain
 Glucose and other vasoactive substances when
increased will increase osmolarity….Vasodilation
 Magnesium – Poweful Vasodilator
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20. Cardiovascular Regulation
 Humoral
Neuronal
 Local
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

21. Neuronal Control
 Responds within seconds
 Components
 Medullary Cardiovascular Control Centres
 Medullary Sympathetic Centre (VASOMOTOR CENTRE)
 Medullary Parasympathetic Centre (NUCLEUS AMBIGUOUS)
 Medullary Relay Centre for Cardiorespiratory & Afferents
(NUCLEUS OF TRACTUS SOLITARIUS)
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

22.  Components
 Autonomic NS supplying The Heart & Blood Vessels
 Regulation by medullary control centres exerted through the ANS
 Sympathetic – Imp in controlling circulation
 Parasympathetic – Contributes to regulation of Heart Fxn
 Afferent Impulses to Medullary Centre
 From higher centres and a large number of other areas
 Skeletal Muscles + Nerves in controlling BP
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23. Medullary Cardiovascular Centres
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24. Vasomotor Centre
 Primary cardiovascular regulatory centre
 Location……………Medulla Oblangata (?Lower Pons)
 Has following areas
 Pressor Area
 Location – RVLM (Rostral Ventro Lateral Medulla)
 Content – Glutaminergic neurons
 Exert excitatory effect on thoracolumbar spinal sympathetic
neurons
 Depressor Area
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

25. Vasomotor Area
 Stimulation of Pressor area
 Arteriolar constriction…….increase in systemic BP
 Venoconstriction……decreases blood stored in venous
reservoir and increases venous return
 +ve Chronotrophic effect (Increase in HR)
 +ve Ionotrophic effect (Increase in force of contraction)
 Neurons here discharge rhythmically in a tonic fashion to
excite sympathetic preganglionic neurons hence continuous
signals passed to sympathetic vasocontrictive nerve fibres
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

26.  Blockage of this tone (e.g. by spinal anaesthesia)
leads to dilatation of blood vessels ….decrease in BP
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27.  Depressor Area
 Location – CVLM (Caudal Ventro Lateral Medulla)..bilaterally
 Stimulation
 Decrease in sympathetic activity due to inhibition of tonically
discharging impulses of pressor area.
 Hence
 Arteriolar dilatation
 Venodilatation
 Decrease in HR
 Decrease in force of contraction
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

28. Medullary Parasympathetic Centres
 Previously – Cardio inhibitory centre
 Specific name – Nucleus Ambiguus
 Neurons here not tonically active
 Receive afferents VIA Nucleus Tractus Solitarius
 Sends inhibitory pathway in form of vagal fibres to the
heart
 Decreases Heart Rate
 Decreases Force of Contraction
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

29. Medullary Relay Station for Cardioresp. Afferents
 Aka – Nucleus Tractus Solitarius of Vagus nerve
 Receive Afferents from most baroreceptors &
Chemoreceptors
 Relays to Vasomotor centre & Nucleus Ambiguus
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

30. Neuronal Control
 Components
 Medullary Cardiovascular control centres
Autonomic NS supplying The Heart &
Blood Vessels
 Afferent Impulses to Medullary Centre
 Skeletal Muscles + Nerves in controlling BP
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

31. Autonomic supply to the Heart
 Sympathetic
 Parasympathetic
 Sympathetic supply
 From spinal sympathetic centre
 Neurons located in intermediolateral horns of spinal cord
 Extends from T1 – L2
 Pre Ganglionic Fibres……small, myelinated
 Post Ganglionic Fibres….Long, Unmyelinated
 Sympathetics from Rt – SA node
 Sympathetics from Lt – AV node
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32. Autonomic Supply to Heart
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34.  Stimulation of sympathetic supply increases
 HR (+ve Chronotropic)…Increases rhythmicity of SAN
 Conductance (+ve Dromotropic)
 Excitability (+ve Bathmotropic)
 Force of contraction (+ve ionotropic)
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

35.  Parasympathetic Supply
 Through both Vagii.
 Preganglionic fibres……long, myelinated
 From nucleus ambiguus
 Postganglionic fibres….Small, unmyelinated
 Distributed to Atria, SAN, AVN and AV Bundle.
 N/B – No vagal motor fibres to ventricles
 Rt Vagus – mainly SAN
 Lt Vagus - AVN
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

36. Decrease in :
. HR
. Impulse conduction
. Excitability of Atria
. Force of contraction of atria
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37. Autonomic Nerve Supply to Blood Vessels
 Has 2 types of effects
 Vasoconstrictive & Vasodilative
 Vasoconstrictive
 By sympathetic fibres supplying blood vessels
 From intermediolateral horns in T1-L2 spinal segment
 Fibres have Norepinephrine, sometimes Neuropeptide
 Stimulation,
 Arteriolar constriction
 Increased PR hence Increased DBP
 Venoconstriction
 Decreased venous capacity hence increased venous return
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

38. Autonomic Supply to Blood Vessels
 Vasodilator Effect
 Decrease in discharge of noradrenergic vasoconstrictor nerves
 Parasympathetic Vasodilator Nerves
 Play limited role in control of general circulation
 Only contribute to pleasure & fulfilling important biological fxns
 Sympathetic cholinergic vasodilator nerves
 Neurotransmitter – Acetylcholine & VasoInhibitory Peptide (VIP)
 Fibres not tonically active and get activated only in biological
stresses e.g during exercise, childbirth, & help in blood flow
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

39. Autonomic supply to Blood Vessels
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41. Neuronal Control
 Components
 Medullary Cardiovascular control centres
 Autonomic NS supplying The Heart & Blood Vessels
Afferent Impulses to Medullary Centre
 Skeletal Muscles + Nerves in controlling BP
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

42. Afferent Impulses to medullary centres
 Afferent Impulses from Higher Centres controlling
vasomotor centres
 Afferent impulses from Respiratory centres
 Cardiovascular Reflex Mechanisms
 Baroreceptor reflex
 Chemoreceptor reflex
 Direct effects on Vasomotor Area
 Cushings Reflex
 CNS ischemia response
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

43. Afferents from Higher Centres
 Cerebral cortex
 Influence on Limbic system results in
 Tachycardia & HTN in sexual excitation and Anger
 Bradycardia & Fainting in sudden emotional shock
 Reticular formation of pons, mesencephalon &
diencephalon influence vasomotor area
 E.g Pain causes increase in BP
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

44. Afferents from Respiratory Centres
 These change vagal tone
 Lead to Sinus Arrhythmia (alterations that occur
during forced breathing).....?normal in young children
 During Inspiration
 Afferents inhibit cardiac vagal centre hence decrease in vagal
tone & Sinus tachycardia
 During Expiration
 Increased vagal tone and Sinus bradycardia
 (Resp centres stop sending inhibitory impulses)
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

45. Cardiovascular Reflex Mechanisms
 Almost all are negative feedback reflex mechanisms
 Include
 Baroreceptor mechanisms
 Chemoreceptor mechanisms
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46. Baroreceptor Reflex Mechanism
 Stretch receptors a.k.a Mechano/Pressure receptors
 Location – Walls of heart and Large blood vessels
 Classification (Functional vs Anatomical)
High Pressure Baroreceptors Low Pressure Baroreceptors
-Monitor Arterial Circulation
-Location
-Carotid Sinus
-Aortic Arch
-Wall of Left Ventricle
-Root of Subclavian
-Junction of thyroid artery
with the common carotid
-A.k.a cardiopulmonary receptors
-Location
-Pulmonary receptors
-Walls of pulm. Trunk &
its divisions
- Atrial receptors
-Wall of right & left Atria
-Entrance of Sup & inf
vena Cava
-Entrance of pulm. veins
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47. Anatomical Classification
Arterial
Systemic
Pulmonary
Cardiac
Atrial
Ventricular
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48. Baroreceptor Reflex
 Reflexes initiated
 Signals enter Tractus Solitarius of medulla
 Secondary signals inhibit vasoconstrictor centre of medulla
and excite vagal parasympathetic centre
 Effect
 Vasodilation of veins and arterioles
 Decrease in heart rate & force of contraction.
 Reflex usually responds much more to a rapidly
changing pressure than stationary
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

49. Baroreceptor Reflex
 Fxn of baroreceptors during change of posture
 On standing, arterial pressure in upper body & head decreases.
Immediate Baroreceptor reflex leads to strong sympathetic
discharge. Minimizes decrease in pressure in upper body
 Pressure Buffer Fxn
 Reduces minute by minute variations in BP occurring with
daily routine activity.
 Opposes either increase or decrease in BP
 Nerves from baroreceptors called buffer nerves
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

50. Baroreceptor Reflex
 Baroreceptor Resetting
 In 1-2 days to whatever pressures that are exposed (adaptive)
 Therefore has NO ROLE in long term regulation.
 E.g. in Chronic HTN, mech. reset to maintain an elevated BP
 Volume Reflex
 Example of Atrial & Pulm artery reflexes.
 Stretch of atria….Reflex dilatation of afferent arterioles in
Kidney
 Also, Signals sent to Hypothalamus to decrease ADH secretion
 Hence increased blood volume reduced back to normal
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

51. Chemoreceptor Reflexes
 Responds to Excess CO2, H+ and Decreased O2
 Not a powerful BP controller in normal range of Bp since are
not stimulated fully until <60mmHg Bps
 Location
 Carotid Bodies and Aortic bodies (adj. to arch of aorta)
 Functions
 Respiratory control
 Cardiovascular control
 Hypoxia
 Increase chemoreceptor discharge…..hyperventilation + VMC
excitation………peripheral vasoconstriction + Increase BP
 Hypotension due to severe haemorrhage
 Increase discharge……………increases BP
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

52. Direct Effect on Vasomotor Area
 Cushings Reflex
 Increase in ICP = Compression of arteries in brain & blood supply to vasomotor
centres.
 Resulting hypoxia + Hypercapnea = Increased VMC discharge = Increased BP =
Restoration of supply to medulla
 Increase in BP also causes reflex bradycardia via baroreceptor response
 CNS ischemic response
 Accumulation of CO2/Lactic acid that excites VMC
 Stimulation leads to vasoconstriction and immediate rise in BP
 Acts as emergency arterial pressure control syst.
 If rise in pressure doesn’t relieve the ischemia, neural cells become inactive (within
3-10min)
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54. Cardiovascular Regulation
 Humoral
 Neuronal
Local
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

55. Acute /Short term control
 Within seconds
 Involves
 Autoregulation
 Metabolic theory/vasodilator theory
 Oxygen lack theory
 Myogenic Theory
 Endothelial Secretions
 Prostacyclin
 NO
 Endothelins
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

56. Role of vasodilator metabolites
(Metabolic/vasodilator theory)
 Accumulation = Increased blood flow
 Potassium and Lactate ions cause vasodilation
 Adenosine may play a role in vasodilation
 Decreased oxygen tension & pH = Vasodilation
 Increased pCO2 = direct dilation action of CO2, more
pronounced in skin and brain.
 Increased temp = Vasodilator effect
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

57.  Therefore, any vasodilator m/lite which accumulates
in tissues during active metabolism will produce
autoregulation.
 By causing increased flow, O2 and other nutrients
provided to tissues. Allows for vasoconstriction and
normal flow despite increased pressures
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

58. Myogenic theory
 Sudden stretch of small blood vessels causes Smooth
Muscles of vessels to contract.
 Increase in BP that stretches blood vessels may cause
reactive vascular constriction that decreases blood
flow nearly back to normal
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

59. Role of Substances released by endothelium
 Prostagladin and Thromboxane A2
 Prostacyclin – Vasodilation
 TxA2 – Vasoconstriction
 Endothelin Derived Relaxing Factor (EDRF)
 A.k.a Nitric Oxide
 Vasodilation
 Leads to eventual production of cGMP = Relaxation of vascular
smooth muscle by decreasing intracellular Calcium ion conc.
 Endothelins
 Vasoconstriction (Most potent agent)
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

60. Other specific local measures
 Tuboglomerular feedback mechanism
 Composition of fluid in early distal tubule detected by Macula
Densa.
 When too much filters from blood, feedback constriction of
afferent arterioles by macula densa hence decrease of renal
blood flow
 CO2 and H+ concentrations controlling blood flow to
brain
 Increase in dilation of cerebral blood vessels = rapid washout
of excess ions and CO2
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

61. Long Term Control
 Days/Months
 Required by
 Ischemic Tissues
 Tissues that grow rapidly
 Tissues becoming chronically hyperactive.
 Pattern and Vasculature Affected
 Increase in physiological size of vessel in tissue &
also number of blood vessels at times
 Low oxygen major factor in stimulating increased
vascularity
Dr. V Chauhan - Cardiovascular Regulation - 22/01/13

62.  Angiogenesis
 Factors
 VEGF – Vascular Endothelial Growth Factor
 FGF - Fibroblast Growth Factor
 Angiogenin
 Development of collateral blood vessels occur
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63. References
 Guyton, Hall. Textbook of Medical Physiology, 10th
Edition
 Ganong F. Review of Medical Physiology, 22nd
Edition
 Khurana I. Textbook of Medical Physiology, 2nd
Edition
 en.wikipedia.org
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