Cardiovascular Homeostasis (LeGrice)

Question 1

Describe the equilibrium between the heart and the vascular system

Answer 1

As the mean right artery pressure increases, venous return decreases

But as the mean right atrial pressure increases, the cardiac output increases.

There is a fine equilibrium so that they maximise the venous return and the cardiac output

Equilibrium In Closed Systems (Vascular Function and Cardiac Function)

Closed systems containing two or more processes whose outputs are determined by a common parameter can operate at a stable equilibrium, e.g. equilibrium between venous return (vascular function) and cardiac output (cardiac function) in CVS system.

• In cardiac function plot, mean right atrial pressure (MRAP) reflects extent of right heart filling. Increase in MRAP leads to increased cardiac output.
• In vascular function plot, venous return to right heart is inversely dependent on MRAP. Increase in MRAP leads to decreased venous return.
  
  • Venous return stops if MRAP is equal to effective pressure driving blood back to heart from peripheral veins.
  • Decrease in MRAP (with respect to this limiting pressure) result in proportionate increases in venous return.
  • Further decrease in MRAP results in MRAP equals to extravascular pressure, and at this point, veins collapse within thoracic cavity limiting any further increase in venous return.

Cardiac function and vascular function plots have been overlaid because both flows are dependent on MRAP. Moreover, because heart and vascular system form a closed circulation, venous return must be the same as cardiac output on average.

• Equilibrium point indicates that there is only one value of MRAP at which venous return and cardiac output are the same.
• It is relatively simple to demonstrate that this is a stable equilibrium at that point.

Question 2

Describe the Regulation Of Cardiovascular Function In Exercise

Answer 2

Integration of Cardiac Function and Vascular Function in Exercise

At rest, cardiac output for a typical adult human is 5-6L/min. With vigorous exercise, this may increase more than 5-fold.

During exercise, there is change in vascular function (curve D).

• There is marked reduction in total peripheral resistance, also _increase in smooth muscle activity in vein_s. Together, these changes increase pressure in peripheral veins driving blood back to heart and give rise to altered vascular function (curve D).
• This results in increased MRAP, which increase cardiac filling.
• This means maximum cardiac output that can be achieved here by increasing vascular function alone is ~13L/min, which is plateau for initial cardiac function (curve A).

Likewise, there is change in cardiac function (curve C) during exercise.

• It produces more vigorous cardiac function, and reduced MRAP at equilibrium point.
• This means maximum cardiac output that can be achieved here by increasing cardiac function alone is ~8L/min, which is the plateau for initial vascular function (curve B)

Outcome to this analysis is that:

• Very large increases in cardiac output seen in exercise can only be achieved if cardiac function is enhanced substantially. But in addition to this, vascular function must also be enhanced to ensure that venous return and cardiac output are matched.
• In exercise, vascular function and cardiac function change in an integrated fashion so that a 5 to 6 folds increase in cardiac output can be achieved with no change (or even a slight drop) in MRAP.

Question 3

Describe the Distribution of Cardiac Output in Exercise

Answer 3

Changes in distribution of cardiac output during exercise reflect operation of further layers of highly sophisticated regulation mechanisms. Primary function of circulation is to distribute sufficient blood to peripheral tissues to meet their metabolic requirements and to return this blood to heart.

Organs supplied by systemic circulation compete for blood flow and proportion of cardiac output, which each organ receives is determined by resistance to blood flow presented by its associated vascular network.

• At rest, CO is distributed relatively uniformly among various organ systems.
• With vigorous exercise, distribution pattern changes markedly.
  
  • Blood is directed preferentially to exercising skeletal (and cardiac) muscle.
    
    • Blood flow to skeletal muscle, ~1L/min at rest, can exceed 20L/min in exercise.
    • Blood flow to heart increases 5-fold from ~250mL/min to >1L/min.
  • Blood flow to brain remains remarkably constant at ~850mL/min.
  • Blood flow to liver, spleen and GI tract (proportion), and blood flow to kidneys (absolute) decreases as a proportion or absolute of cardiac output.

There is tight linkage between increased blood flow and increased oxygen consumption during exercise. It appears that mechanisms operating to regulate distribution of blood flow are ensuring:

• Blood flow is increased (routed) to organ systems with an i_mmediate requirement for metabolic support;_
• Blood flow is decreased to organ systems that can (at least in short term) tolerate a reduction.

How is this apparently optimal use of “scarce” blood flow achieved?

Question 4

What are the intrinsic and extrinsic factors that control the CVS

Answer 4

Extrinsic

• ANS
• Endocrine System

Question 5

Describe the parasympathetic System (where it originates)

Answer 5

Pre-ganglionic parasympathetic fibres originate in brainstem, and travel in CN III, VII, IX & X (X most important). They also originate in segments S2-S4.

Pre-ganglionic parasympathetic fibres synapse at ganglia located in or near walls of viscera.

They innervate viscera via short post-ganglionic axons.

Question 6

Describe the Sympathetic System

Answer 6

Sympathetic System

Pre-ganglionic sympathetic axons originate in thoraco-lumbar region of spinal cord (T1-T12, L1-L3).

Most pre-ganglionic sympathetic axons synapse in paravertebral ganglion chain.

They innervate viscera via relatively long post-ganglionic nerves.

• Some pass directly through paravertebral ganglion chain and synapse at collateral ganglia close to organs/glands they supply.
• Post-ganglionic sympathetic nerves to head, neck, lungs and heart originate in superior cervical, middle cervical and stellate ganglia (three upper ganglia in the paravertebral ganglion chain).

Question 7

Describe how the Endocrine System controls the CVS

Answer 7

Endocrine System

Other than ANS, the other extrinsic cardiovascular control system is endocrine system (adrenaline, RAAS, ADH, NP).

Adrenal Medulla

Adrenal medulla synthesizes and stores endogenous catecholamines adrenaline (80%) and noradrenaline (NA) (20%).

Arenal medulla receives preganglionic sympathetic innervation and sympathetic activation causes adrenaline and noradrenaline (to a lesser extent) to be released into bloodstream.

Renin-Angiotensin-Aldosterone System (RAAS)

The seat of renin-angiotensin-aldosterone cascade is juxtaglomerular apparatus (JGA) associated with terminal segment of renal afferent arterioles. JGA contains granules of renin enzyme, which is released into bloodstream in response to:

• Sympathetic stimulation via b1 receptors
• Decreased pressure in afferent arterioles
• Decreased sodium load at macula densa

Renin converts circulating plasma protein angiotensinogen (a2-globulin) into angiotensin I (vasoinactive substance).

Angiotensin I is converted into _angiotensin II (_potent vasoconstrictor), by angiotensin converting enzyme (ACE) found mainly in brush border of lung capillaries.

Anti-Diuretic Hormone (ADH)

Anti-diuretic hormone (ADH) or vasopressin regulates renal water handling. It increases water reabsorption via aquaporin-2.

ADH is also vasoconstrictor at physiological concentrations.

Natriuretic Peptides

Natriuretic peptides (ANP, BNP) are synthesized by heart, brain and other organs. Its release by heart is stimulated by (1) atrial and ventricular distension; and by (2) neurohumoral stimuli, usually in response to heart failure.

Question 8

How do Angiotensin II affect the CVS?

Answer 8

Angiotensin II has powerful and widespread effects on cardiovascular system:

• It penetrates blood-brain barrier at postrema area in hypothalamus. This in turn:
  
  • Activates descending pathways which modulate sympathetic outflow to cardiovascular system and adrenal medulla.
  • Facilitates synthesis of antidiuretic hormone (ADH) and stimulates thirst.
• It potentiates ganglionic transmission which facilitates neurotransmission at the paravertebral ganglia.
• It increases _synthesis and release of NA fr_om sympathetic nerve terminals and inhibits its reuptake. Therefore, sympathetic neurotransmission is facilitated in both the heart and vessels.
• It acts directly on vascular smooth muscle to cause constriction.
• It promotes increased formation and release of aldosterone from adrenal cortex.
  
  • This results in increase in Na+ reabsorption (and K+ excretion) by renal tubules.
  • In this way, system can exert a powerful medium-term effect on cardiovascular function by influencing extracellular fluid volume (increase volume via water reabsorption following Na+), and hence b_lood volume._

Question 9

What are Natriuretic Peptides and what do they do?

Answer 9

Natriuretic peptides serve as a counter-regulatory system (antagonists) for RAAS.

Natriuretic peptides (ANP, BNP) are synthesized by heart, brain and other organs. Its release by heart is stimulated by (1) atrial and ventricular distension; and by (2) neurohumoral stimuli, usually in response to heart failure.

Together, these actions lead to:

• ↓ Blood volume
• ↓ Arterial pressure
• ↓ Central venous pressure
• ↓ Pulmonary capillary wedge pressure
• ↓ Cardiac output.