Cardiovascular Physiology Definitions

Afterload

The tension that the heart must overcome to eject blood. It is largely determined by arterial pressure. In other words, the tension or stress that builds up in the ventricular wall during ejection is referred to as afterload. While afterload is closely associated with systemic vascular resistance for the left ventricle (or pulmonary vascular resistance for the right ventricle), it is also influenced by alterations in ventricular size and thickness.

When examining the graph of contractility versus afterload, it becomes evident that as afterload increases, contractility decreases. This relationship is particularly pronounced in the neonatal myocardium due to its immaturity, resulting in a steeper decline. The effect is also more pronounced for the right ventricle (RV) compared to the left ventricle (LV), with the RV being more "intolerant" of increased afterload unless it has adapted to a chronic elevation. Consequently, the RV is more prone to acute failure in response to a sudden rise in afterload, such as during a pulmonary vasoconstriction crisis.

Atrial pressure wave curve

In an atrial pressure waveform, the "a" wave represents atrial contraction, the "c" wave corresponds to the onset of systole with bulging of the tricuspid valve into the right atrium during ventricular contraction, and the "v" wave reflects the filling of the atrium against a closed tricuspid valve during ventricular systole; essentially, the "a" wave is the active filling of the atrium, the "c" wave is a passive pressure change due to the tricuspid valve movement, and the "v" wave is the passive filling of the atrium against a closed valve.

Right atrium

The a wave is higher than the v wave in the right atrium typically, while the v wave is higher than the a wave in the left atrium. The difference in the prominence of the a wave and v wave between the right atrium (RA) and left atrium (LA) is primarily due to differences in compliance, resistance, and pressure gradients in the right and left heart circuits. In infants, the mean right atrial pressure typically ranges from 0 to 4 mmHg, with lower a and v waves observed. In premature neonates, RA pressures tend to be even lower. 

Left atrium

Characterized by a prominent v wave. v wave dominance is not directly linked to the LV or systemic circulation but reflects pulmonary blood flow and is transmitted from the pulmonary arteries. 

Autoregulation

Autoregulation refers to the ability of an organ or tissue to maintain a consistent level of blood flow despite changes in perfusion pressure. It is a physiological mechanism essential for ensuring that critical tissues, such as the brain, heart, and kidneys, receive adequate oxygen and nutrients under varying conditions, such as changes in blood pressure.

Autoregulation is achieved through two primary mechanisms: 

Cerebral Autoregulation: Maintains consistent blood flow to the brain, critical for neuronal function. Sensitive to changes in carbon dioxide (CO₂) and oxygen (O₂) levels. 

Renal Autoregulation: Protects kidney function by stabilizing glomerular filtration rate (GFR) despite fluctuations in systemic blood pressure. Mechanisms include the myogenic response and tubuloglomerular feedback. 

Coronary Autoregulation: Adjusts blood flow to the heart muscle based on myocardial oxygen demand.

Bernoulli Principle

States that an increase in the speed of a fluid occurs simultaneously with a decrease in pressure or potential energy. The Bernoulli Principle is a fundamental concept in fluid dynamics that describes the behavior of a fluid moving along a streamline. It states that in a steady, incompressible flow with negligible viscosity, the total mechanical energy of the fluid remains constant. This principle implies that an increase in the fluid's speed leads to a decrease in its pressure or potential energy, and vice versa. The Bernoulli Principle states that for an incompressible, non-viscous fluid flowing in a streamline, the sum of the pressure energy, kinetic energy, and potential energy per unit volume remains constant.


Assumptions and Limitations: 

Boyle's Law

Boyle's Law states that the pressure of a given mass of gas is inversely proportional to its volume, provided the temperature remains constant. This means that if the volume of the gas increases, the pressure decreases, and vice versa. This relationship implies that the product of the initial pressure and volume is equal to the product of the final pressure and volume.

Dalton's Law

States that the total pressure exerted by a mixture of gases is equal to the sum of the partial pressures of the individual gases.

Fick's Law

Describes the rate at which a substance (e.g., a gas) diffuses across a membrane. It is dependent on the surface area, the concentration gradient, and the membrane's permeability. It quantifies how the concentration of a substance changes over time due to diffusion.

Flow-pressure interaction

Flow-Pressure Interaction refers to the relationship between fluid (liquid or gas) flow and the pressure driving that flow. Pressure Gradient: The difference in pressure between two points in a fluid system that drives the flow. Fluids move from areas of high pressure to areas of low pressure. Flow Rate: The volume of fluid passing through a cross-sectional area per unit time, typically measured in liters per minute (L/min) for liquids or liters per second (L/s) for gases. 


Factors Affecting Flow-Pressure Interaction: 


Dynamic changes:

Force-frequency relationship

The Force-Frequency Relationship (FFR) describes how the contractile force of cardiac muscle changes with varying frequencies of stimulation. This relationship is crucial in understanding how the heart responds to different rates of electrical stimulation and adapts its force of contraction accordingly. Generally, within physiological limits, an increase in the frequency of stimulation leads to an increase in the force of contraction. However, this follows a "U" shape, and at high frequency this may lead to decrease in cardiac function. One key important concept is that coronary perfusion is dependent on the diastolic aortic blood pressure relative to the right atrial pressure, since the coronary sinus drains into the right atrium in the majority of cardiac configurations. The force-frequency relationship thus refers to the connection between heart rate and contractility. To a certain extent, the myocardium adapts to maintain contractility at higher heart rates, compensating for inadequate filling time. However, this adaptation does not apply in the context of heart failure. Reduced filling time also impacts coronary perfusion. Medications that optimize heart function may increase heart rate, but they do not result in a synergistic increase in contractility, leading to a blunted force-frequency relationship. 

Frank-Starling Law

The Frank-Starling Law (also known as the Frank-Starling mechanism or Starling's law of the heart) is a fundamental principle in cardiac physiology. It describes the relationship between the volume of blood filling the heart (the end-diastolic volume) and the force of cardiac contraction (stroke volume). This law explains how the heart is able to adjust its pumping capacity to accommodate varying volumes of incoming blood. The Frank-Starling Law states that the force of the heart's contraction is directly proportional to the initial length of the cardiac muscle fibers (preload). In other words, an increase in the volume of blood filling the heart (end-diastolic volume) leads to a stronger contraction and greater stroke volume. The Frank-Starling mechanism ensures that the volume of blood the heart pumps out matches the volume of blood returning to it. This balance is crucial for maintaining consistent blood flow and pressure. In heart failure, the Frank-Starling mechanism may be impaired. The heart may not be able to increase its force of contraction in response to increased preload, leading to inadequate cardiac output. Conditions that lead to fluid overload can excessively stretch the heart muscle fibers, moving them beyond the optimal point on the Frank-Starling curve and resulting in reduced contractility. Cardiomyopathies: Diseases that affect the structure or function of the heart muscle can alter the Frank-Starling relationship.


Neonatal vs adult curve is flatter unless you are at lower filling pressures. As such, administration of significant amount of volumes in the context of normal preload is unlikely to improve neonatal myocardial contractilty, expect in infants with hypertrophic cardiomyopathy or other etiologies with restrictive non-compliant hearts in which higher preload may be necessary to improve contractility by the Frank Starling Law. 

Source: Wikipedia

Gas Diffusion 

The process by which gas molecules spread from an area of high concentration to an area of lower concentration.

Gas Solubility 

The ability of a gas to dissolve in a liquid, influenced by temperature, pressure, and the nature of the gas and liquid.

Hagen-Poiseuille Equations

The Hagen-Poiseuille Equation describes the flow of an incompressible, Newtonian fluid in a long, straight cylindrical pipe with a constant circular cross-section. This equation is fundamental in fluid dynamics and helps to understand the factors affecting laminar flow through vessels and tubes. The Hagen-Poiseuille equation quantifies the volumetric flow rate of a fluid through a cylindrical pipe, considering factors such as fluid viscosity, pipe length, radius, and pressure difference. The equation assumes laminar flow. It does not apply to turbulent flow, which occurs at higher flow rates or in larger pipes. It is valid only for Newtonian fluids, where the viscosity remains constant regardless of the flow conditions. The equation does not account for factors like pipe roughness or bends in the pipe, which can significantly affect flow in practical situations.


Assumptions regarding flow within a vessel are based on the following principles: the fluid must be Newtonian, the flow should be laminar, the fluid must be non-compressible, and the flow should be non-accelerating. Key factors that influence this flow include pressure, resistance, blood viscosity, and the diameter of the vessel.


Effect on Pulmonary vasculature (theoretical concepts and unproven)

 

Effect of Systemic vasculature (theoretical concepts and unproven)

Henry's Law

Henry's Law describes the relationship between the partial pressure of a gas above a liquid and the concentration of that gas dissolved in the liquid. Henry's Law states that at a constant temperature, the amount of a gas that dissolves in a liquid is directly proportional to the partial pressure of that gas in equilibrium with the liquid. It explains how oxygen and carbon dioxide dissolve in blood. For example, the amount of oxygen that dissolves in the blood is proportional to the partial pressure of oxygen in the alveoli.

Hooke's Law

Hooke's Law describes the behavior of elastic materials when they are deformed by an external force. This law states that the force needed to extend or compress a spring by some distance is proportional to that distance. It describes the relationship between the force applied to an elastic object and the resulting deformation. The restoring force is the force exerted by the material to return to its original shape. The negative sign in the equation indicates that this force is in the opposite direction of the applied force (restorative). Hooke’s Law is valid only within the elastic limit of the material. Beyond this limit, the material may deform plastically (permanently) or fracture.


Relevant in the hypertrophic ventricles who are stiffer (poor compliance) - small changes in volume will lead to much higher degree increase in pressure. The compliant heart tends to have smaller increase in pressure with the same degree of increased volume.

Laplace's Law

Relates the pressure within a spherical or cylindrical object to the tension in the wall and the radius of the object.

Preload

Preload is a critical concept in cardiovascular physiology that refers to the initial stretching of the cardiac myocytes (heart muscle cells) prior to contraction. It is closely related to the volume of blood returning to the heart and filling the ventricles at the end of diastole (the relaxation phase of the cardiac cycle). Preload is a key determinant of stroke volume and cardiac output. Preload is often reflected by the end-diastolic volume (EDV) or end-diastolic pressure (EDP) that stretches the ventricles of the heart to their greatest geometric dimensions under variable physiologic demand. It reflects the volume of blood in the ventricles at the end of diastole before the heart contracts. Determinants of preload: 

See other resources: here and here

Pressure Gradient

The difference in pressure between two points in a fluid system, which drives the flow of the fluid.

Stress-Velocity Relationship

The relationship between the stress on the heart muscle and the velocity of muscle shortening during contraction. The Stress-Velocity Relationship describes how the velocity of muscle shortening during contraction is related to the applied stress (force per unit area) on the muscle. This relationship is crucial in understanding the mechanical properties and performance of muscle tissues, including cardiac muscle. It describes how the speed (velocity) at which a muscle fiber shortens is inversely related to the load (stress) it is under. This principle is particularly important for understanding how muscles generate force and movement. Stress-Velocity Relationship is typically represented by a hyperbolic curve when force (stress) is plotted against velocity. As the load on the muscle increases, the velocity of shortening decreases, approaching zero as the muscle generates its maximum isometric force. In the heart, the stress-velocity relationship helps to explain how the heart muscle adapts to different loading conditions. Under higher afterload (increased stress), the velocity of contraction decreases, affecting the rate of blood ejection from the ventricles. Consider a scenario where a muscle is lifting a weight. As the weight (load) increases, the speed at which the muscle can lift the weight decreases. Conversely, when the muscle lifts a lighter weight, it can do so more quickly. This inverse relationship illustrates the basic principle of the stress-velocity relationship.

Compliance/Elastance: 

Compliance is the ability of a hollow organ to stretch and expand. Elastance is the ability to return to its original shape after deformation.

Ventriculo-arterial coupling

The relationship between the ventricle and the arterial system, influencing cardiac performance and efficiency. Ventriculo-arterial (VA) coupling describes the relationship between the mechanical properties of the heart (ventricle) and the arterial system. It is an important concept in cardiovascular physiology as it reflects the efficiency of the heart in pumping blood and the arterial system in accommodating and distributing that blood. Ventricular Elastance (Ees): Represents the contractility or the stiffness of the ventricle during systole. It is the slope of the end-systolic pressure-volume relationship (ESPVR). Arterial Elastance (Ea): Represents the arterial load or afterload. It is a measure of the arterial system’s opposition to the blood ejected by the ventricle. Ea can be approximated by the ratio of end-systolic pressure (ESP) to stroke volume (SV): Ea=ESP/SV. VA coupling is assessed using pressure-volume loops obtained through invasive hemodynamic monitoring. These loops provide detailed information about the relationship between pressure and volume throughout the cardiac cycle. Optimal VA coupling minimizes the cardiac energy expenditure for a given cardiac output, reducing myocardial oxygen demand and enhancing overall cardiovascular efficiency.

 Viscosity

A measure of a fluid's resistance to flow.

Wall tension (Law of Laplace)

The force exerted in the wall of a blood vessel or cardiac chamber. Wall tension refers to the force per unit length exerted circumferentially in the wall of a cylindrical structure, such as a blood vessel or the heart's ventricle, due to the pressure of the fluid inside it. The Wall tension is often described by the Law of Laplace. In blood vessels, wall tension helps to maintain structural stability and regulate blood flow. In the heart, wall tension affects myocardial oxygen demand and is related to conditions such as hypertrophy and heart failure. Increased wall tension in the ventricles can lead to cardiac hypertrophy (thickening of the heart muscle) as an adaptive response to reduce tension. It may also compromise coronary blood flow. The Law of Laplace provides a simplified model and assumes uniform pressure and wall thickness, which may not be the case in all physiological or pathological conditions. Real biological tissues have complex, anisotropic properties, meaning their mechanical behavior can vary in different directions.

Work (Cardiac)

Cardiac work refers to the amount of energy the heart expends to pump blood throughout the circulatory system. Cardiac work is the energy the heart uses to eject blood against arterial pressure during each cardiac cycle. It is typically expressed as the work done per minute, known as the cardiac power output. 

Windkessel Effect 

The Windkessel Effect refers to the ability of large elastic arteries (such as the aorta) to dampen the pulsatile nature of blood flow generated by the intermittent ejection of blood from the heart, thus ensuring a more steady flow through the smaller arteries, arterioles, and capillaries. This effect is crucial for maintaining continuous blood flow during both systole (when the heart contracts) and diastole (when the heart relaxes). "Windkessel" is a German word that translates to "air chamber" or "reservoir." The concept was originally used to describe air-filled chambers in early firefighting water pumps that helped to smooth out the flow of water. Systole: During the contraction phase of the cardiac cycle, blood is ejected into the large elastic arteries (e.g., the aorta). The walls of these arteries stretch to accommodate the increased volume of blood. Diastole: During the relaxation phase, the elastic recoil of the artery walls helps to maintain pressure and drive blood forward into the smaller arteries and capillaries, even though the heart is not actively pumping at this time. The Windkessel effect helps to ensure continuous blood flow through the capillaries, even when the heart is between beats. By damping the pulsatile output of the heart, the Windkessel effect helps to reduce the workload on the heart and prevent damage to the microcirculation.

Hemodynamics is Physiology

Presentation given in the context of the NHRC by Dr Patrick McNamara

July 10th, 2024: Amazing presentation by Dr Patrick McNamara on Physiology. The Youtube recording is now available. This talk was given in the context of the NHRC Foundation Curriculum. I invite you all to listen to this great review of cardiovascular physiology and cardio-pulmonary interactions.

10 juillet 2024 : Présentation du Dr Patrick McNamara sur la physiologie. L'enregistrement Youtube est maintenant disponible. Cette conférence a été donnée dans le contexte du programme de la Fondation NHRC. Je vous invite tous à écouter cette grande revue de la physiologie cardiovasculaire et des interactions cardio-pulmonaires.

fped-06-00087.pdf
biology-13-00055.pdf

Wiggers Diagram of cardiac physiology

Obtained from Wikipedia - adh30 revised work by DanielChangMD who revised original work of DestinyQx; Redrawn as SVG by xavax, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons

https://upload.wikimedia.org/wikipedia/commons/9/91/Wiggers_Diagram_2.svg 

Mullaly R, El-Khuffash AF. Haemodynamic assessment and management of hypotension in the preterm. Arch Dis Child Fetal Neonatal Ed. 2024 Feb 19;109(2):120-127. doi: 10.1136/archdischild-2022-324935. PMID: 37173119.

120.full.pdf
EPIQ_Blood pressure guidelines_ver June 29_2022.pdf
A_Physiologic_Approach_to_Hemodynamic_Monitoring_a.pdf

Hassan R, Verma RP. Neonatal Hypertension. [Updated 2022 Oct 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK563223/ 

Presentation by Dr Carolina Michel Macias on Hypotension in prematurity given for the NH-TNE fellowship training program at McGill on September 30, 2024

HypotensionPrem.pdf

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