Cardio Summary

Roles of the Cardiovascular System

• Transport:
  • Supplies cells with O_2, nutrients, and substrates.
  • Removes waste products.
  • Transports endocrine hormones and neurotransmitters.
• Immune Function:
  • Facilitated by specialized blood cells.
• Heat Regulation:
  • Shunts blood from the core to the surface to remove heat, and vice versa.
  • Organ and whole-body heat regulation depends on blood flow.
• Body Fluid Regulation:
  • Influences fluid volume to regulate blood pressure (BP) and control heart rate (HR).
• Endocrine Function:
  • Example: Atrial natriuretic peptide (ANP), a vasodilator released from the myocardium.
• Adequate blood tissue and perfusion are essential for life; inadequacy leads to permanent cell damage or death.

Model of Physiological Regulation

• Controlled variables operate over a wide range.
• Regulated variables have a narrower range of operation.

The Heart: A Dual Pump System

• Drives blood in two serial circuits:

  1. Pulmonary Circuit:

     • Low-pressure system with thinner atrium walls.
     • Goal: Re-oxygenation of deoxygenated blood.
     • Involves the right side of the heart.
     • Atrioventricular (AV) Valve (Tricuspid):
       • Prevents backflow into the atria.
       • Contains 3 leaflets (cusps) and 3 papillary muscles connected via chordae tendineae.
     • Pulmonary Semilunar Valve:
       • Prevents backflow into the right ventricle.
       • Opens when right ventricle (RV) pressure is greater than pulmonary artery pressure.
       • Opens when pressure is higher.
       • Snaps shut when pressure is higher in the trunk than in the ventricle.
       • Directs blood flow to the lungs for re-oxygenation.

  2. Systemic Circuit:

     • High-pressure system that pumps blood throughout the body.
     • Goal: Delivery of oxygenated blood to cells.
     • Involves the left side of the heart.
     • Atrioventricular (AV) Valve (Mitral/Bicuspid):
       • Prevents backflow into the atrium.
       • Contains 2 leaflets (cusps) and 2 papillary muscles connected via chordae tendineae.
     • Aortic Semilunar Valve:
       • Prevents backflow into the left ventricle.
       • Opens when left ventricle (LV) pressure is greater than aortic pressure.
       • Directs blood to the systemic circulation.

Blood Flow Through the Heart

• Two circuits operate in parallel.
• Deoxygenated Blood Flow:
  • Superior vena cava and coronary sinus bring blood back to the right atrium.
  • Drains into the right ventricle via the tricuspid valve.
  • The atrium contracts slightly before the ventricle to finish filling it.
  • Blood is forced out through the pulmonary semilunar valve into the pulmonary trunk.
  • Flows through the lungs for re-oxygenation.
• Oxygenated Blood Flow:
  • Oxygenated blood returns through the pulmonary veins to the left atrium.
  • Drains into the left ventricle through valves.
  • The ventricle contracts and forces blood out through the aortic semilunar valve.
  • Blood circulates through the body, where cells use the oxygen.
  • Deoxygenated blood returns to the right atrium, and the process restarts.

Electrical Excitation of the Heart

• Sinoatrial (SA) Node:
  • Primary pacemaker.
• Atrioventricular (AV) Node:
  • Secondary pacemaker.
• Impulse Path:
  • AV node → AV bundle → Purkinje fibers → muscle cells.
• The heart contracts up and out to eject blood through the semilunar valves.

Action Potential in Contractile Cells (Atrial and Ventricular)

1. Depolarization:

   • Na^+ influx through fast voltage-gated Na^+ channels reduces the negative membrane potential.

2. Plateau Phase:

   • Some K^+ channels open (loss of positive charge) but Ca^{2+} channels also open (positive influx).
   • This phase is important for the heart to act as an effective pump.

3. Repolarization:

   • Ca^{2+} channels close and K^+ channels open, leading to K^+ efflux.
   • Restores negative membrane potential, allowing the heart to relax and refill.
   • Essential for preventing constant action potentials.

Action Potential in Pacemaker Cells (SA Node and AV Node)

1. Slow Opening of Na^+ Channels:

   • Reduces negative membrane potential.

2. Reaching Threshold:

   • Ca^{2+} gates open, allowing Ca^{2+} inflow, causing depolarization.

3. Repolarization:

   • Ca^{2+} channels close, K^+ channels open, causing K^+ efflux.
   • Restores negative membrane potential, restarting the process.

• The pacemaker determines the slope and rate of sodium influx.

Electrocardiogram (ECG)

• Records electrical activity of the heart.
• P Wave:
  • Represents depolarization of the atria.
• P-Q Interval:
  • Represents the time the action potential travels through myocytes before reaching the AV node (approximately 0.1 second).
• QRS Complex:
  • Represents depolarization of the ventricles and some repolarization of the atria.
• QRS Complex and T Wave Delay:
  • Occurs as the heart contracts.
• T Wave:
  • Represents repolarization of the ventricles.
• Between T and P Wave:
  • Slow leak of sodium into pacemaker cells.

Cardiac Cycle

• Systole:
  • Ejects most, but not all, blood out of the heart chambers.
• Cardiac Output (CO):
  • Volume of blood pumped by the heart in one minute.
  • CO = Heart Rate (HR) \, \text{x} \, Stroke Volume (SV)
  • Resting CO = ~5.4 L/min = 60 beats/min x 90 ml/beat
• Stroke Volume (SV):
  • Difference between end-diastolic volume (EDV) and end-systolic volume (ESV).
  • SV = EDV - ESV
  • EDV: Amount of blood in the ventricle during diastole.
  • ESV: Amount of blood remaining in the ventricle after contraction.

Blood Pressure

• Force of blood against the vessel wall.
• Higher during systole and lower during diastole.
• Expressed as systolic/diastolic (e.g., 120/80 mmHg).
• Average healthy adult BP = 120/80 mmHg.
• Pulse Pressure:
  • Pulsation of blood propelled into the arteries following ventricular contraction (systole).
  • Systolic - Diastolic = ~40 mmHg.
• Mean Arterial Pressure (MAP):
  • Important pressure to consider because arterial pulse pressure fluctuates with each heartbeat.
  • Diastole lasts longer than systole; thus, MAP is not simply the average of systolic and diastolic pressures.
  • MAP = \text{Diastolic Pressure} + \frac{1}{3} \text{Pulse Pressure}
  • MAP = \sim 93 \text{ mmHg (120/80)}

Cardiac Output Hemodynamics

• The beating left side of the heart provides pressure to drive blood flow.
• Ohm's Law for Hydrodynamics:
  • \text{Pressure Difference} = \text{Flow Rate} \, \text{x} \, \text{Resistance}
  • The pressure difference between an upstream point (p1 e.g., aorta) and a downstream site (p2 e.g., vena cava) equals the product of flow (F) and resistance (R) between those points, assuming consistent radius.
• Blood Flow:
  • Depends on the pressure gradient (main driving force) and resistance (hindrance to flow due to friction).
• Pressure Gradient:
  • Blood flows from high to low pressure, down the intravascular pressure gradient.
  • The main driving force; without it, there is no flow.
• Increase pressure difference = increase in flow, decrease in pressure difference = decrease in flow.
• Maintaining flow rate impacts velocity.

Pressure Components

• Blood Pressure:
  • Pressure generated by the heart.
• Hydrostatic Pressure:
  • Force exerted by a fluid pressing against a wall; affected by gravity.
  • HP = \text{density of fluid} \, \text{x} \, \text{acceleration due to gravity} \, \text{x} \, \text{height of fluid volume}

Resistance

• Opposition to flow, occurring in the periphery (vessels away from the heart).

• Called peripheral resistance.

• Depends on:

  1. Length (L) of Vessels:

     • Increased length = increased resistance.
     • Pressure drops along the length of the tube.
     • Doubling the length halves the flow rate.
     • Increased length = increased surface for friction, slowing flow.
     • Blood flow is inversely proportional to changes in blood vessel length.
     • Length is relatively constant in the body.

  2. Viscosity (\eta) of Blood:

     • Increased viscosity = increased resistance.
     • Increased viscosity = decreased flow (when pressure is constant).
     • Increased viscosity = increased friction = increased resistance = decreased flow.
     • Viscosity is inversely proportional to blood flow.
     • Viscosity is relatively constant.

  3. Radius (r) of Vessels:

     • Increased radius = decreased resistance.
     • Flow is reduced when force is maintained, but tube diameter is smaller, due to resistance.
     • Decreased radius = increased friction = increased resistance = decreased flow.
     • Most important/powerful effect on flow in the body.
     • Organ blood flow is regulated by controlling vessel radius.
     • Doubling the radius = 16-fold increase in flow.
     • Blood flow is proportional to the fourth power of changes in radius.
     • Flow \propto r^4
     • Not kept constant in the body; impacts resistance significantly.

• Aggregate flow (total flow) does not differ between vessel types, even though the radius changes because the total cross-sectional area negates the effects of decreased tube length and radius.

Anatomical Arrangement of Vessels

1. Serial Arrangement:

   • Reduces flow (volume/time), but velocity (distance/time) is increased in serially arranged small vessels.
   • Adding sections will always result in increased resistance and reduced flow (increased vessel length).
   • R = R1 + R2 + R_3 + …

2. Parallel Arrangement:

   • Increases flow (volume) in parallel vessels (lower resistance).
   • One vessel branching into many = lower resistance (increased combined radius).
   • Adding sections will always result in decreased resistance.
   • \frac{1}{R} = \frac{1}{R1} + \frac{1}{R2} + \frac{1}{R_3} + …

• Depends on pressure gradient = main driving force for flow AND resistance - hindrance to flow (created by friction)

Poiseuille's Law

• Developed in 1846.
• Provides a good representation but is 100% accurate only for rigid cylindrical tubes.
• Blood vessels are not completely rigid.
• \text{Flow} = \frac{\Delta P \pi r^4}{8 \eta L}, where \Delta P is the pressure difference, r is the radius, \eta is viscosity, and L is the length of the tube.

Blood Vessel Wall Structure

• Fibers providing vessel rigidity:
  • Elastic fibers: allow stretching and recoil.
  • Collagen (fibrous) fibers: less extensible, resist stretching.
• Changes in blood vessel dimensions are mainly circumferential, influenced by:
  • Active factors: via smooth muscle.
  • Passive factors: relaxed vessel, but tension in the wall resists pressure (elastin/collagen fibers).

Transmural Pressure

• Governs vessel diameter.
• Difference between intravascular pressure and external pressure.
• TP = r1 - r2 (where r1 is pressure inside the vessel, and r2 is pressure outside the vessel).
• A vessel can expand if transmural pressure is positive (r1 > r2).
• Eg: if r1 = 25 \text{ mmHg} and r2 = 15 \text{ mmHg}, then TP = 10 \text{ mmHg}.
• Eg. if r1 = 15 \text{ mmHg} and r2 = 25 \text{ mmHg}, then TP = -10 \text{ mmHg}.

Compliance

• Ease of vessel expansion with positive transmural pressure, resulting in volume change.
• Rigid-walled vessels: less compliant.
• Arterioles (resistance vessels): lots of smooth muscle but minor elasticity.
• Elastic-walled vessels: more compliant.
• Veins (capacitance vessels): accept large blood volumes without increased pressure.

Compliance Types

• Zero Compliance:
  • Cannot add any further volume once the vessel is full (no 'give' in the walls).
  • Can handle high pressure due to full resistance.
• Infinite Compliance:
  • Can add further volume with no pressure increase.
• Finite Compliance:
  • A bit of extra volume causes a bit of extra pressure as walls of vessel distend.

Conductance

• Ability of a blood vessel to accept blood flow for a given pressure gradient.
• The greater the resistance, the lower the blood vessel conductance (reduced blood flow).
• Low conductance vessels = arterioles (resistance vessels).
• High conductance vessels = veins (capacitance vessels).

Conductance Influences Blood Volume Distribution

• Most of the blood volume resides in the systemic veins (~65%).
• Therefore, changes in vein diameter cause a major impact on central blood volume (volume of heart chambers and pulmonary circuit) and blood pressure.
• Low pressure = pooling; radius = fourth power changes on flow (major effect on cardiac output).

Blood Volume Distribution

• 85% systemic, 10% pulmonary, 5% in heart chambers.
• Systemic Circulation:
  • 20% arterial.
  • 65% venous.
• 15% in high-pressure vessels, 80% in low-pressure vessels.

Organ Blood Distribution

Organ Blood Distribution at Rest

• Blood volume = 5L
• Heart rate = 60 bpm
• CO = 5L/min
• At rest a lot of our blood flow is being sent to organs involved in digestion and waste removal at rest.

Organ Blood Distribution with Moderate Exercise

• Blood volume = 5L
• Heart rate = 120 bpm
• CO = 12.5 L/min
• Less than 10% of blood is going to organs involved in digestion and waste removal.
• More blood flow is now going to skeletal muscles and body surface to remove heat, increased flow to the heart

Blood Pressure Profiles

Blood pressure Profiles

• Radius of vessel rarely constant.
• Vessel can expand if transmural pressure it +ve
• Eg. if r1 = 25 and r2 = 15 mmHg then TP = 10 mmHg
• Eg. if r1 = 15 and r2 = 25 mmHg then TP = -10mmHg
• Distension acts to absorb blood pressure:

Blood pressure absorption by Vessel Distension

• Smooths/lowers systemic pressure swings.
• Lowers systolic pressure into the rest of vessels.
• Sustains constant blood flow (as it contracts and heart goes into diastole).
• Stroke volume (70-90ml) delivered to aorta at high velocity, every heartbeat (60 bpm).
• Aortic flow varies: 70ml/sec (peak flow) to -10ml/sec (flow reversal prior to aortic valve closure).
• Differences between peak pressure and minimal pressure are being reduced because distension lowers systemic pressure versus a rigid vessel wall (absorbs pressure).
• Vessels absorb elastic energy during distension (systole).
• Return during diastole.
• Aortic flow near values = 0 during diastole, but elastic recoil of arteries maintains pressure above 0 in downstream vessels to force blood flow through rest of vessels
• Distension acts to absorb blood pressure, smooths/ lowers systemic pressure swings.
• The steepest drop in blood pressure occurs at arterioles (resistance vessels).

Vascular Smooth Muscle (VSM)

• Found in arteries, arterioles, pre-capillary sphincters, and large veins.
• Proportional increase in VSM as arteries become smaller, relative to elastic tissue.
• Example: VSM ≈ 25% > elastic tissues in arteries but ≈ 100% in arterioles.
• VSM activation: Refers to as ‘myogenic tone’

VSM activation

• Vasoconstriction:
  • Decreased vessel diameter (arteries, arterioles, sphincters, and veins).
  • Active construction: Increased myogenic tone = decreased vessel diameter.
• Vasodilation:
  • Increased vessel diameter.
  • Passive dilation: Reduced myogenic tone = VSM relax = increased vessel diameter.
  • Active dilation: Stretch VSM in some vessels = decreased myogenic tone = increased vessel diameter.
• Vasoconstriction can lead to a 20-50% decrease in arterial diameter.
• Systemic arteries can hold ~700ml blood
• Therefore, maximal construction = ~ 350ml blood volume reduction in arteries
• Systemic veins can hold more (~3200 mls blood)
• Venoconstriction is less powerful than vasoconstriction, but even a 20% diameter construction = ~ 650ml blood volume reduction

Pre-Capillary Sphincters

• Smooth muscle rings located at the entrance to capillaries.
• Regulate perfusion of the capillary bed.
• Respond to changes in local tissue states: Chemical, thermal, hormonal (mostly not innervated).
• Look after local blood flow (i.e., relax to increase blood flow to capillary bed).

Capillary Pressure and Resistance

• VC or VD either side of capillaries influences their pressure with respect to precapillary and postcapillary pressures with resistance
• Normal State:
  • Pre-capillary resistance > post-capillary resistance.
  • Pressure in capillary is much closer to venous pressure because the biggest drop in pressure will be across resistance between arteriole and capillary
• Precapillary pressures relative to post capillary pressure changes alter capillary pressure relative to them

Shifts in Capillary Pressure

• Increase in Post-capillary / Reduction in Pre-capillary Pressure:

  • Biggest change in pressure will happen between capillary and vein.
  • Capillary pressure rises and moves closer to arteriole pressure (PC \rightarrow PA).

• Increase in Pre-capillary Pressure:

  • Much greater resistance before the capillary compared to after.
  • Even bigger drop in capillary pressure.
  • Capillary pressure moves more towards venus pressure

Regulated Variables

• Pressures (and therefore flow)
  • Blood pressure (mean arterial pressure)
  • Central venous pressure.

Why MAP is Important

• The CV system allows flexibility for distributing blood flow, mostly by controlling systemic mean arterial pressure.
• MAP has to be high enough to allow increased flow to any bed if needed, without losing flow to other houses.
• Provided:
  • MAP is maintained high enough:
    • To ensure brain perfusion when standing.
    • For very high vascular resistance in the eye.
    • For the high pressure needed for glomerular filtration.

Why CVP is Important

• The pressure inside the large systemic veins leading to the right side of the heart.
• CVP is the main determinant of right atrial filling (maintaining enough pressure).
• Affects martial filling pressure.
• Filling pressure determines intrinsic contractility (Starling's Law: Intrinsic control).
• Eg. Systemic flow: right ventricle (water tower) creates enough pressure to cause flow to go to all our capillary beds at the rate that is required, then returning back to right side of the heart and CVP.

Baroreceptors

• Detect these pressures (CVP and MAP).
• High-pressure and low-pressure baroreceptors.
• HP: focused on MAP regulation; LP: focus on volume regulation and cardiac filling

High Pressure Baroreceptors

• In the arterial system, especially the carotid sinus and aortic arch.

• Nerve endings -> the receptors are in areas of high compliance - more elastic tissue increases pressure.

• Responds depending on pressure and stretch around them back to the medulla.

• Located at:

  • Carotid Sinus:
    • a distensible portion of the internal carotid artery.
  • Aortic Arch:
    • Highly compliant, distends with each left ventricular ejection.

• Stretch distorts the receptor = afferent nerve impulse via CN 9 and CN 10

• Located in highly compliant vessels (distensible).

• Receptors are bare nerves.

• Increased pressure = increased stretch = increased receptor potential increases.

• Located in areas of hugh compliance (distensible).

Receptor Potential

• Input (e.g., neurotransmitter or stretch) activates the receptor, activating ion channels, triggering a current = membrane depolarization in sensory afferent nerve fibers
• High stretch = increase receptor potential.
• Inward current depolarizing the nerve membrane.
• Stretch causes ion channels to open and changes receptor potential.

Biphasic Response

• Initial repolarization is large (dynamic overshoot).
• Settles into modest steady-state (static) component of receptor potential.

Graded Response

• Amplitude and frequency proportional to stretch input.
• Firing rate is proportional to the change in amplitude of blood pressure, giving more information.
• High pressure = high receptor firing and high receptor recruitment = high intensity of afferent firing
• Receptor saturation at 200 mmHg (all receptors recruited).
• During exercise:
  • Baroreceptor sensitivity reduces in proportion to intensity.

Baroreceptor Resetting

• Baroreceptors can reset after several days and desensitize if overworked.
• Baroreceptors are only short-term response mechanisms.

Carotid Sinus Receptors

• More sensitive than aortic arch receptors.
• Similar to carotid body vs. aortic body (carotid more responsive to chemical changes).

High-Pressure Baroreceptor Mechanism

• An increase in MAP leads to generalized vasodilation + bradycardia (slows heart rate).
• Receptor stimulation reduces blood pressure.
• Decrease in MAP leads to generalized vasoconstriction + tachycardia (speeds heart rate).
• Mediated via the medullary cardiovascular center.
• The efferent pathway slows heart rate (bradycardia) and vasodilation reduces resistance.
• If cardiac output and total peripheral resistance are reduced, there will be a drop in blood pressure -> brings MAP back to normal.
• If MAP drops -> tachycardia (increased heart rate) and vasoconstriction HPB interact with chemoreceptors: Co-localization (carotid + aortic).
• Input from HPB and chemoreceptors both decrease heart rate (bradycardia) but have opposite effects on vascular tone.

Low-Pressure Baroreceptors

• Located in the junction of vena cava and right atrium, right and left atria, right ventricle, pulmonary arteries, and the junction of the left atrium and pulmonary veins.
• Receptors are bare nerves that fire afferent signals to the medulla.
• Increased volume = increase pressure = increase stretch = increase receptor potential = increase afferent firing = FULL
• Distension depends largely on venous return to the heart (stretching).
• Control the circulating volume of blood.
• Regulate body fluid and blood volume.
• Indirectly regulate MAP.

Types of Low Pressure Baroreceptors

• A-type:

  • Signal heart rate to the brain and are located on artieral mainly in body of right atrium.
  • Located on ‘A-fibers’ of afferent axons joining CN X.
  • Fire with atrial systole (contraction) - note ECG timing.

• B-type:

  • Most common low-pressure baroreceptors found mainly in superior and inferior vena cava but located in the remaining low-pressure sites
  • Located on different set (B) of fibers of afferent axons joining CN X.
  • Depend largely on venous return to the heart for distension.
  • Signal circulating volume and venous return
  • Gradually increase firing during atrial diastole (filling).
  • Primarily monitor circulating volume and CVP

• Increased B-type LPB firing due to increased venous return

  • Renal vasodilation, increases renal blood flow, increase filtration = increase urination = decrease blood volume
  • renal specificity (vs. HPB general vasodilation)
  • Tachycardia- increase heart rate, increases renal blood flow increase filtration, increase urination decrease blood volume
  • Opposite to HPB

Bainbridge Reflex

• Tachycardia caused by increased venous return
• Net effect of increased atrial stretch = increase diuresis, attempting to eliminate fluid in response to stretch.

Mechanisms for Atrial Stretch Leading to Dilution

1. Renal Vasodilation + Tachycardia:

   • Reduced renal SNS activity = increased renal blood flow.

2. Atrial Natriuretic Hormone (ANP):

   • Atrial myocytes release ANP in response to stretch.
   • Powerful vasodilator = diuresis.
   • Increase Na+ excretion (natriuresis = diuresis, as water follows Na+).

3. Inhibition of Antidiuretic Hormone (ADH/Arginine Vasopressin):

   • Arterial stretch afferent to the medulla via CN X synapses with neurons signaling to the hypothalamus (inhibiting input to the posterior pituitary gland).
   • ADH = decrease diuresis; thus, decrease ADH = increased diuresis.

Baroreceptor Afferent Pathways

• High-Pressure Baroreceptors:
  • Carotid afferents: via CN IX
  • Aortic afferents: via CN X
• Low-Pressure Baroreceptors:
  • Afferents: via CN X
• Both target:
  • Medulla oblongata (medullary cardiovascular center)
  • LPB can activate the hypothalamus.

Role of Cortex

• Stress can cause fainting (brief hypotension); central integrator, medulla oblongata.

Role of Central Integrator: Medulla

• Baroreceptors (carotid sinus, aortic arch, LPBR) sends afferent signaling via CN IX and X to the medulla:

  • Nucleus of the Solitary Tract (NTS):
    • Afferent sensory integrator found in the dorsal medulla.
    • NTS -> vasomotor area -> vasoconstriction (pressor effect): increased BP due to vasoconstriction:
    • Thoracic spinal cord -> preganglionic sympathetic fibers traveling to sympathetic trunk ganglion -
    • Post ganglionic sympathetic fibres travelling out to the heart and vessels

• Thoracic spinal cord = symp. Innervation to heart (increase HR and contractility) AND arterioles / venules (Constriction).

• Most vascular beds in body exhibit SNS constrictor tone.

• Unless inhibited, vasomotor area = vasoconstriction.

• Adrenal medulla releases epinephrine to increase SNS activity.

If Passive Vasodilation is Needed (Depressor Effect):

• Inhibitory neurons from the NTS block the vasomotor area/SNS constrictor tone.
• EXAMPLE: HPBR increases generalized MAP vasodilation to reduce blood pressure = RECALL.
• Increased MAP = Increased HPBR afferent firing = NTS inhibitory neuron firing = vasomotor area inhibition = decreased constrictor tone = passive vasodilation = decreased MAP.
• This accounts for the main vascular component of the baroreceptor reflex.

Cardio-Inhibitory Area (CIA)

• If need cardiac deceleration.

• Excitatory Neurons from the NTS project to the CIA:

  • Comprised of the dorsal motor nucleus of the vagus nerve + nucleus ambiguus.
  • Stimulates parasympathetic output to the heart.
  • Vagal innervation to the heart.
  • Axons = parasympathetic preganglionic neurons (vagus nerve).

• The main cardiac component of the baroreceptor reflex (Bradycardia)is increased firing of baroreceptors (slowing of the heart).

Cardio-Acceleratory Area

• May be inhibited or activated (removal of inhibition) by neuron inputs from NTS = Bradycardia and decreased contractility, or tachycardia and increased contractility, repressively.

Efferent Pathways to Effectors

Sympathetic Vasoconstrictor Pathways to Blood Vessels

• Neurons from the medulla project axons to the thoracic spinal cord.
• Preganglionic sympathetic neurons synapse on the sympathetic trunk ganglion.
• SNS vasoconstriction postganglionic axons are widely distributed throughout blood vessels in multiple regions of the body.
• Most abundant in kidneys (fluid regulation) and skin (thermoregulation).
• Release noradrenaline (norepinephrine) onto adrenergic receptors expressed by vascular smooth muscle cells.

Sympathetic (Ach) Vasodilator Pathways to Blood Vessels

• Efferent signals arise from the hypothalamus and innervate pre-capillary vessels.
• Release acetylcholine onto postsynaptic cholinergic receptors expressed by vascular smooth muscle cells.
• Myocyte relaxation and passive vasodilation
• Skin and muscle receive both sympathetic vasoconstrictor and vasodilator fiber innervations.
• Note: Poor evidence for Ach role in human skeletal muscle but likely important during initial vasodilation in skin (comes from animals).

Parasympathetic Vasodilator Pathways to Blood Vessels

• Less distribution of PNS vasodilator fibers on blood vessels in the body in comparison to SNS
• Found in salivary and gastrointestinal glands and erectile tissues.
• Neurons from medulla project axons down the cranial vagus nerve (CN X) and sacral spinal cord.
• Indirect vasodilation: PS axons released ACh onto cholinergic receptors located on ganglion sympathetic nerve fibers.
• Inhibiting contractor tone causing vasodilation(Ach binds to muscarinic GPCR = cAMP inhibition of norepinephrine release from post-ganglionic sympathetic nerve terminals for example in Skeletal muscle vessel)

Sympathetic Pathway to Adrenal Medulla

• Sympathetic preganglionic fibers innervate chromaffin cells of the adrenal medulla.
• ACh onto ACh-R on chromaffin cells.
• Chromaffin cells mainly release epinephrine (adrenaline) and some NE, via endocrine= whole- body response= tachycardia and vasoconstriction).

Sympathetic Pathways to the Heart

• Neurons from medulla project axons to the thoracic spinal cord.
• Preganglionic sympathetic neurons synapse on the sympathetic trunk ganglion.
• SNS postganglionic axons become cardiac nerves
• Innervate SA nodes (major pacemaker in right atria) (SNS minor impact on HR) and contractile cells (SNS major impact on contractility).
• Release noradrenaline (norepinephrine) onto adrenergic receptors expressed by pacemaker and contractile cells.
• Binding increases ion channels that change membrane polarization.
• Increases force of muscle contraction of the heart

Parasympathetic Pathways to Heart

• Neurons from medulla project axons down the vagus nerve (CN X).
• Synapse on postganglionic neurons in parasympathetic ganglia (in the heart).
• PNS postganglionic axons are short
• Innervate SA nodes (PNS major impact on HR), atria, and ventricles (very minor impact on contractility).
• Release acetylcholine (ACh) onto receptors expressed by pacemaker/contractile cells.

Modulation of Pacemaker Activity

• Na+/Ca2+ high in concentration outside the cell
• K+ high in concentration inside the cell
• Resting membrane potential of a cardiac muscle cell ~90 mV, SA node ~ 60mV.
• Why?
  • Negatively-charged proteins inside the cell that cannot escape
  • The cell membrane is leaky to K+ (more positive charge going outside the cells).
  • Na+ or Ca2+ into cells (depolarisation).
  • K+ out (repolarisation/hyperpolarisation)

ACth and catecholamines influence the SA node

• ACh slows pacemaker firing by three mechanisms
  • Increased parasympathetic tone = increased ACh binding to cholinergic receptors on SA node where:

ACth influence in pacemaker cells by:

1. Pacemaker Current (I_f) is Slowed (Elongated):
   *steepness