SUMMARY OF IMPORTANT CV PHYSIOLOGY CONCEPTS

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CV INTRO Large organisms require a circulatory system so that metabolic substrates and byproducts of cellular metabolism can be efficiently exchanged between cells and the outside environment, as well as transported to distant sites within the body. Venous blood returns to the right side of the heart, which pumps the blood into the pulmonary circulation where oxygen and carbon dioxide are exchanged with the gases found within the lung alveoli. Oxygenated blood from the lungs enters the left side of the heart, which pumps the blood at high pressure into the aorta for distribution to various organs via large distributing arteries. Small capillaries within the organs serve as the primary site of nutrient exchange. Blood flow within organs is determined primarily by the arterial pressure and by changes in the diameters of blood vessels within the organs brought about by contraction or relaxation of smooth muscle within the walls of the blood vessels. Most major organ systems are in parallel with each other so that blood flow in one organ has relatively little influence on blood flow in another organ. Negative feedback mechanisms such as the baroreceptor reflex, acting through autonomic nerves and circulating hormones, help to maintain normal arterial pressure.

SUMMARY OF IMPORTANT CV PHYSIOLOGY CONCEPTS

CV ELECTRIAL ACTIVITY SUMMARY OF IMPORTANT CONCEPTS The membrane potential is determined primarily by the concentration of sodium, potassium, and calcium ions across the cell membrane, and by the relative conductances of the membrane to these ions. The resting membrane potential is very close to the potassium equilibrium potential (calculated from Nernst equation) because the relative conductance of potassium is much higher than the relative conductances of sodium and calcium in the resting cell. Ions move across the cell membrane through ion-selective channels, which have open (activated) and closed (inactivated) states that are regulated by either membrane voltage or by receptor-coupled mechanisms. Concentrations of sodium, potassium, and calcium across the cell membrane are maintained by the Na+/K+-ATPase pump, the Na+/ca++ exchanger, and the Ca++ATPase pump. Nonpacemaker cardiac action potentials are characterized as having very negative resting potentials (approximately -90 mV), a rapid phase 0 depolarization produced primarily by a transient increase in sodium conductance, and a prolonged plateau phase (phase 2) generated primarily by inward calcium currents through L-type calcium channels; increased potassium conductance repolarizes the cells during phase 3. Pacemaker action potentials (e.g., those found in SA nodal cells) spontaneously depolarize during phase 4, owing in part to special pacemaker current. Upon reaching the threshold for action potential generation, calcium conductance increases as L-type calcium channels become activated, which causes depolarization (phase 0). As the calcium channels close, potassium conductance increases and the cell repolarizes (phase 3). At rest, SA nodal pacemaker activity is strongly influenced by vagal activity (vagal tone), which significantly reduces the intrinsic SA nodal firing rate. Pacemaker activity is increased by sympathetic activation and vagal inhibition. Conduction of action potentials within the heart is primarily cell-to-cell,although specialized conduction pathways exist within the heart that ensure rapid distribution of the conducted action potentials. Conduction velocity is increased by activation of sympathetic nerves and decreased by parasympathetic activation. The low conduction velocity within the AV node ensures sufficient time for atrial contraction to contribute to ventricular filling.

SUMMARY OF IMPORTANT CV PHYSIOLOGY CONCEPTS

 Cells located within the AV node and ventricular conducting system can also serve as pacemakers if the SA node fails or conduction is blocked between the atria and ventricles (AV block). The ECG evaluates rhythm and conduction by examining the appearance (amplitude, duration, and shape) of specific waveforms that represent atrial depolarization (P wave), ventricular depolarization (QRS complex), and ventricular repolarization (T wave). Different ECG leads view the electrical activity of the heart from different angles. Each limb lead can be represented by an electrical axis on a frontal plane from which the direction of depolarization and repolarization vectors within the heart can be determined using standard rules of interpretation (e.g., a wave of depolarization traveling toward a positive electrode produces a positive voltage in the ECG. Chest leads (V1, to V 6) measure the electrical activity in a horizontal plane that is perpendicular to the frontal plane. CV CELLULAR STRUCTURE AND FUNCTION The basic contractile unit of a cardiac myocyte is the sarcomere, which contains thick filaments (myosin) and thin filaments (actin, troponin, and tropomyosin) that are involved in muscle contraction. Excitation-contraction coupling is initiated by depolarization of the cardiac myocyte, and is controlled by changes in intracellular calcium, which binds to regulatory proteins on the thin filaments; ATP is required for contraction and relaxation. Relaxation of cardiac myocytes (lusitropy) is primarily regulated by the reuptake of calcium into the sarcoplasmic reticulum by the SERCA pump. The contractile function of cardiac myocytes requires large amounts of ATP, which is generated primarily by oxidative metabolism of fatty acids and carbohydrates, although the heart is flexible in its use of substrates and can also metabolize amino acids, ketones, and lactate. Arteries and veins are arranged as three layers: adventitia, media, and intima. Autonomic nerves and small blood vessels (vasa vasorum in large vessels) are found in the adventitia; vascular smooth muscle is found in the media; and the intima is lined by the endothelium. Vascular smooth muscle contains actin and myosin; however, these components are not arranged in the same repetitive pattern as that found in cardiac myocytes. Unlike cardiac muscle contraction, vascular smooth muscle contraction Is slow and sustained.

SUMMARY OF IMPORTANT CV PHYSIOLOGY CONCEPTS

 Cardiac muscle contraction is regulated by various substances that bind to receptors coupled to G-proteins. Vascular smooth muscle contraction/ relaxation is additionally regulated by NO/cGMPdependent pathways. All these pathways largely affect contraction/relaxation primarily by regulating intracellular calcium. The vascular endothelium synthesizes nitric oxide and prostacyclin, both of which relax vascular smooth muscle. Endothelin-1, which is also synthesized by the endothelium, contracts vascular smooth muscle. VASCULAR FUNTCION Regulation of arterial pressure and organ blood flow Is primarily the function of the small resistance vesselsarteries and arterioles. Capillaries are the principal site for exchange and most of the blood volume is found in the venous capacitance vessels. Mean arterial pressure is determined by the product of cardiac output and systemic vascular resistance, plus CVP. Aortic pulse pressure is primarily determined by ventricular stroke volume and aortic compliance. Vascular resistance s inversely related to the vessel radius to the fourth power, and it is directly related to vessel length and blood viscosity. Vessel radius is the most important factor for regulating resistance. The parallel arrangement of vascular beds in the body reduces overall resistance. Furthermore, because of this arrangement, a resistance change in one vascular bed has minimal influence on pressure and flow in other vascular beds. Changes in large artery resistance have little effect on total resistance of a vascular bed because these vessels normally comprise only a small percentage of the total resistance of a vascular bed. In contrast, changes in small artery and arteriolar resistances greatly affect total resistance. Arteries and veins are normally in a partially constricted state (i.e., they possess vascular tone), which is determined by the net effect of vasoconstrictor and vasodilator influences acting upon the vessel. CVP is altered by changes in thoracic blood volume and venous compliance.
SUMMARY OF IMPORTANT CV PHYSIOLOGY CONCEPTS

Gravity, respiratory activity, and the pumping action of rhythmically contracting skeletal muscle have important influences on CVP. Cardiac output is strongly influenced by changes in systemic vascular function as described by cardiac and systemic vascular function curves. In the normal heart, cardiac output is limited by factors that determine vascular function.

CARDIC FUNCTION The cardiac cycle is divided into two general phases: diastole and systole. Diastole refers to the period of time that the ventricles are undergoing relaxation and filling with blood from the atria. Ventricular filling is primarily passive, although atrial contraction has a variable effect on the final extent of ventricular filling (EDV). Systole represents the time when the ventricles are contracting and ejecting blood (SV). The volume of blood remaining in the ventricle at the end of ejection is the ESV. Normal heart sounds (S1 and S2) originate from abrupt closure of heart valves. Ventricular SV is the difference between the end-diastolic and endsystolic volumes. Ventricular ejection fraction (EF) is calculated as the SV divided by the EDV. Cardiac output is normally influenced more by changes in heart rate than by changes in SV; however, impaired regulation of SV can have a significant adverse effect on cardiac output, as occurs during heart failure. Ventricular preload is related to the extent of ventricular filling (EDV) and the sarcomere length. Increased preload increases the force of contraction and SV. Ventricular afterload can be estimated by ventricular wall stress, which is the product of ventricular pressure and ventricular radius divided by the ventricular wall thickness. Increased afterload decreases the velocity of fiber shortening during contraction, which decreases the SV. lnotropy is the property of a cardiac myocyte that enables it to alter its tension development independent of changes in preload length. Increased inotropy enhances active tension development by individual muscle fibers and increases ventricular pressure development, ejection velocity, and SV at a given preload and afterload. Preload, afterload, and inotropy are interdependent, meaning that a change in one usually leads to secondary changes in the others. Myocardial oxygen consumption can be calculated using the Fick Principle, in which oxygen consumption equals the product of the CBF and the arteriovenous oxygen difference.
SUMMARY OF IMPORTANT CV PHYSIOLOGY CONCEPTS

Myocardial oxygen consumption is strongly influenced by changes in arterial pressure, heart rate, and inotropy; it is less influenced by changes in SV.

Reference: Klabunde RE, Cardiovascular Physiology Concepts, Second Edition LLW, 2011 Online Study http://www.cvphysiology.com/textbook.htm

SUMMARY OF IMPORTANT CV PHYSIOLOGY CONCEPTS