Control of Cardiac Output and Blood Pressure

Importance of Cardiac Output (CO) and Mean Arterial Pressure (MAP)

• Cardiac output (CO) and mean arterial blood pressure (MAP) are crucial and need to be regulated.

Lecture Objectives

• Explain the importance of cardiac output and mean arterial blood pressure and the need to regulate them.

• Describe the processes that determine stroke volume and heart rate.

• Explain total peripheral resistance and what determines it.

• Describe the baroreceptor reflex for the short-term control of MAP and the factors that contribute to it.

• Describe the role of the RAAS and ANP in the long-term control of MAP via regulation of blood volume.

Lifetime Cardiovascular Activity

• Approximately 250 million heartbeats.

• Approximately 17 million liters of blood pumped.

The Cardiovascular System

• Requirement for Regulation: The cardiovascular system regulates the delivery/transport of substances in response to changing environmental or organismal needs to facilitate homeostasis.

• Transport Medium: Substances are transported in blood, necessitating regulation of blood flow.

• Diffusion Limitations: Diffusion alone is sufficient only in single-celled and simple multicellular organisms for oxygen and nutrient delivery and waste removal.

• Complex organisms need a circulatory system to transport substances around the body by bulk flow.

Components of the Cardiovascular System

• Heart: Pumps blood and generates flow.

• Aorta: Main artery.

• Vena Cava: Main vein.

• Capillaries: Facilitate the exchange of gases, fluids, nutrients, and waste products.

• Arterioles: Main resistance vessels that control regional blood flow, containing endothelium and smooth muscle.

• Venules: Capacitance vessels with wide lumens, endothelium, few elastic layers, and few smooth muscle layers.

• Large Veins: Low resistance, high capacitance vessels with several elastic layers and many smooth muscle layers.

• Large Arteries: Low resistance, conducting vessels.

Key Concepts: Flow and Pressure

• Cardiac Output (CO): The total blood flow through the body, approximately $5L/min$$$5L/min$$ at rest.

• Relationship: Flow and pressure are directly proportional i.e. $Flow \propto Pressure$$$Flow \propto Pressure$$ or $Pressure \propto Flow$$$Pressure \propto Flow$$.

• Importance of Blood Pressure: It is essential to support blood flow throughout the body.

• Generation of Blood Flow: Occurs through the pumping action of the heart.

Basic Catch-Up Questions

• Flow: Movement of a substance.

• Pressure: Force generated by molecules moving, necessitates pressure difference.

MAP Fluctuations

• MAP is maintained within normal limits over the long-term but fluctuates in the short-term due to various factors (e.g., fluid balance, posture, exercise, sleep).

Darcy's Law

• $$P1 - P2$or$$$ or $$\Delta P = F \times R$$ (Pressure difference = Flow x Resistance).

• Regulation: MAP can be regulated by controlling CO and TPR.

• Formula: $MAP = CO \times TPR$$$MAP = CO \times TPR$$

  • MAP: Mean Arterial Pressure

  • CO: Cardiac Output (total flow)

  • TPR: Total Peripheral Resistance

Importance of Maintaining MAP

• Necessity: MAP must be maintained within normal limits to prevent insufficient or excessive blood flow to sensitive organs like the brain and kidneys.

• Balancing Act: Regulating MAP requires fine-tuning of CO, TPR, and MAP itself.

• Exercise Considerations: During exercise, metabolic demand, and consequently total blood flow, must increase without excessively raising MAP.

• High Pressure Risks: Prolonged high pressure can lead to stroke, kidney damage, and heart failure.

• Low Pressure Risks: Insufficient blood flow can cause fainting and gangrene.

Determinants of Cardiac Output

• $MAP = CO \times TPR$$$MAP = CO \times TPR$$

• Stroke Volume (SV): Volume of blood heart ejects.

Changes in Stroke Volume

• Venous return and the Frank-Starling mechanism.

• Cardiac muscle contractility (inotropy).

• Venous capacitance.

• Blood volume.

Changes in Heart Rate (Chronotropy)

Key Facts About Cardiac Output

• Total blood flow around the body (5L/min on average at rest).

• Product of stroke volume (SV, volume of blood ejected per heartbeat) and heart rate (HR): $CO = SV \times HR$$$CO = SV \times HR$$

• The heart consists of two pumps in series: the systemic and pulmonary circulations are in series with each other.

• Outputs from the left ventricle (LV) and right ventricle (RV) must be equal over time ($$CO{LV} = CO{RV}$$).

• Heart rate is always the same on both sides, but transient imbalances in SV can occur.

• Mechanisms exist to correct these imbalances.

• SV and HR can be regulated independently.

Determinants of Stroke Volume

• Influence of venous return.

• Effects of changes to venous capacitance and total blood volume.

• Effects of inotropic stimuli on contractility.

Stroke Volume and Venous Return

• Stroke volume is influenced by venous return: increased venous return leads to increased stroke volume via the Frank-Starling mechanism.

• Frank-Starling Mechanism: Filling pressure determines the degree of stretch of a ventricle immediately before it contracts.

• Increased venous return increases filling pressure of the atria and ventricles, leading to increased stroke volume.

The Frank-Starling Mechanism

• Stretching the muscle increases sarcomere length.

• Greater contractile force without a change in $[Ca^{2+}]_i$$$[Ca^{2+}]_i$$.

• The sensitivity of contractile fibers to $Ca^{2+}$$$Ca^{2+}$$ increases.

Match Outputs

• The Frank-Starling mechanism matches outputs from right and left ventricles.

  • Temporary mismatch between RV and LV output is corrected through this mechanism.

Factors Altering Venous Return

Venous Capacitance Changes

• Orthostasis (standing): Gravity pulls blood into the lower body, reducing venous return and central venous pressure; veins are distended (increased capacitance).

• Dynamic Exercise: Increases venous return through muscle and respiratory pumps and active constriction of veins, increasing central venous pressure.

Blood Volume Changes

• Drop in Blood Volume: Reduces venous return and central venous pressure; caused by diuresis, diarrhea, or blood loss.

• Increase in Blood Volume: More difficult to achieve; can be caused by eating too much salt, hormonal imbalances, or transfusion.

• Regulation: Blood volume regulation involves the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS).

Myocardial Contractility

• Stroke volume is influenced by altering myocardial contractility, affecting both ventricles simultaneously.

• Positive Inotropes (e.g., adrenaline, noradrenaline): Increase the force of contraction of cardiac muscle, leading to increased stroke volume.

Control of Heart Rate

• Regulation by the autonomic nervous system.

Heart Rate and Metabolic Demand

• Heart rate is adjusted to meet changes in metabolic demand.

• Sleep: Low metabolic demand, low heart rate, low cardiac output.

• Strenuous Exercise: High metabolic demand, high heart rate, high cardiac output.

Autonomic Control

• Control of heart rate is autonomic, involving opposing actions of the sympathetic and parasympathetic nervous systems.

• Parasympathetic Nervous System (Vagus Nerve): Decreases HR.

• Sympathetic Nervous System: Increases HR, faster rate of Action Potential.

Chronotropic Effects

• Positive Chronotrope: Increases heart rate.

• Negative Chronotrope: Decreases heart rate.

• The SNS (noradrenaline) and PNS (acetylcholine) act on the sinoatrial (SA) node (pacemaker).

Pacemaker Potential

• Pacemaker potential: Steadily depolarizing resting potential; when it reaches the threshold, an action potential is triggered.

• Sympathetic Stimulation: Increases the slope of the pacemaker potential, increasing heart rate.

• Parasympathetic Stimulation: Decreases the slope of the pacemaker potential, decreasing heart rate.

Explanation of the Cardiac Pacemaker

• The cardiac pacemaker in the SA node initiates the heartbeat and sets the basic rhythm of cardiac contraction.

• The SA node generates the action potential, which spreads throughout the heart, causing the atria and ventricles to contract.

• The SA node regulates heart rate (beats per minute) and is controlled by the autonomic nervous system.

• The sympathetic NS releases noradrenaline to increase HR, while the parasympathetic NS releases acetylcholine to decrease HR.

• The SA node has an unstable membrane potential called the pacemaker potential, which slowly depolarizes.

• When the membrane potential depolarizes to the threshold potential, it triggers an action potential, causing the heart to contract.

• The rate at which the membrane potential depolarizes determines how quickly the next heartbeat occurs.

• Sympathetic stimulation increases the slope of the pacemaker potential, increasing HR, while parasympathetic stimulation decreases the slope, slowing HR.

Summary of Cardiac Output Determinants

• Factors influencing cardiac output include:

  • Stroke volume (myocardial stretch, venous constriction, blood volume, cardiac contractility).

  • Heart rate (sympathetic and parasympathetic activity).

• An increase in CO caused by increased blood volume, physical activity, or stimuli that increase venous return or activate the sympathetic NS/inhibit the parasympathetic NS.

• A decrease in CO is caused by decreased blood volume, physical inactivity/sleep, or stimuli that inhibit venous return or inhibit the sympathetic NS/activate the parasympathetic NS.

Determinants of Total Peripheral Resistance

• $MAP = CO \times TPR$$$MAP = CO \times TPR$$

Control of Total Peripheral Resistance

• TPR is regulated by altering the radius of arterioles.

• Reducing tube radius increases resistance, leading to increased pressure upstream.

• Resistance is inversely proportional to the fourth power of the radius: $Resistance \propto \frac{1}{radius^4}$$$Resistance \propto \frac{1}{radius^4}$$.

Arterioles

• Arterioles can actively adjust their radius through vasoconstriction or vasorelaxation.

• Vasoconstriction reduces radius and increases resistance.

• Vasodilation increases radius and reduces resistance.

Vasoconstrictor Stimuli

• Noradrenaline (SNS).

• Adrenaline.

• Angiotensin II (RAAS).

• Vasopressin (ADH).

Vasodilator Stimuli

• Adrenaline.

• Atrial natriuretic peptide.

• Histamine.

Short-Term Control of MAP

• The baroreceptor reflex integrates the control of cardiac output (SV x HR) and TPR to control blood pressure.

Components of the Baroreceptor Reflex

• Rapid response to changes in MAP and pulse pressure.

• Sensors: Baroreceptors in the carotid sinuses/aortic arch.

• Integrating Center: Medulla of the brain.

• Effectors: Heart rate and contractility, venous return, blood volume (via kidneys), and arteriolar radius.

• Mechanism: Negative feedback via adjustments to CO and TPR.

Baroreceptor Reflex

• Rapid short-term response to decreased blood volume and MAP will restore MAP through negative feedback.

RAAS

• Reduced blood volume and MAP leads to increased renin secretion and angiotensin II production, which restores blood volume.

Long-Term Control of MAP

• Involves control of blood volume via aldosterone and ANP.

Key Facts About Blood Volume

• Blood volume is coupled to blood pressure via the Frank-Starling mechanism.

• Plasma is a major constituent of total body extracellular fluid.

• Total body extracellular fluid volume is coupled to total extracellular fluid $Na^+$$$Na^+$$ content.

• Reduced $Na^+$$$Na^+$$ content decreases plasma volume, increased $Na^+$$$Na^+$$ content increases plasma volume.

• Stabilizing extracellular $Na^+$$$Na^+$$ content in the long-term stabilizes blood volume and MAP.

The Renin-Angiotensin-Aldosterone System

• RAAS regulates plasma volume in the long-term and maintains MAP.

• Macula densa cells sense changes in plasma volume via changes in glomerular filtration rate (GFR) and $Na^+$$$Na^+$$ delivery.

• Decreased plasma volume and MAP lead to reduced GFR and enhanced renin secretion.

Long Term Correction

• Long-term correction for decreased plasma volume occurs via increased renal $Na^+$$$Na^+$$ reabsorption.

Atrial Natriuretic Peptide (ANP)

• ANP opposes the actions of the RAAS and decreases plasma volume.

Long-Term Correction

• Long-term correction for increased plasma volume occurs via decreased renal $Na^+$$$Na^+$$ reabsorption.

Summary of MAP Determinants

• Mean arterial pressure (MAP) is determined by cardiac output (CO) and total peripheral resistance (TPR).

• CO influenced by stroke volume and heart rate, and TPR influenced by vasoactive hormones and local factors.

Additional functions:

• Preventing postural hypotension

• Diving reflex

• Cardiovascular responses to exercise