VPSL 121 Module III Lecture 1-2 Cardiovascular Function PDF

VPSL 121 Module III Lecture 1- Overview of Cardiovascular Function Lesson 2- Electrical Activity of the Heart Overview of Cardiovascular Function KEY POINTS: 1. The normal cardiovascular function is essential for life and health- cardiovascular function and dysfunction 2. Cardiovascular dysfunctions reflect primary cardiovascular disturbances or diseases, but often are secondary consequences of non-cardiovascular disturbances or diseases. 3. Substances transported by the cardiovascular system include nutrients, waste products, hormones, electrolytes, and water. 4. Two modes of transport used in the cardiovascular system: bulk flow and diffusion. 5. Diffusion is very slow so every metabolically active cell in the body must be close to a capillary carrying blood by bulk flow. 6. The pulmonary and systemic circulations are arranged in series, but the various organs within the systemic circulation are arranged in parallel. Overview of Cardiovascular Function 7. Cardiac output- volume of blood pumped each minute by one ventricle. 8. The perfusion pressure for the systemic circulation is much greater than the perfusion pressure for the pulmonary circulation. 9. Each type of blood vessel has physical properties suited to each particular function. 10. Blood is a suspension of cells in extracellular fluid (plasma). 11. The cellular component of blood includes red blood cells, white blood cells, and platelets. 12.Oxygen in blood is carried in chemical combination with the protein hemoglobin within red blood cells. 1. Normal Cardiovascular Function Is Essential for Life and Health-Understand Cardiovascular Function and Dysfunction Cardiovascular physiology - the study of the function of the heart, the blood vessels, and the blood. The primary function of the cardiovascular system: transport Substances transported are essential for life and health- ex. oxygen and nutrients carries carbon dioxide and other metabolic waste products away from metabolically active cells- go to the lungs, kidneys, or liver, where they are excreted. if the heart stops contracting and circulation ceases: unconsciousness results within about 30 seconds, and irreversible damage to the brain and other sensitive body tissues occurs within a few minutes. 1. Normal Cardiovascular Function Is Essential for Life and Health-Understand Cardiovascular Function and Dysfunction circulation does not stop completely the loss of as little as 10% of the normal blood volume can impair exercise performance normal function depends on the delivery of adequate blood flow. The higher the rate of metabolism in a tissue, the greater is the requirement for blood flow ischemia- condition of inadequate blood flow to any tissue transient ischemia leads to dysfunction Persistent ischemia leads to permanent tissue damage (infarction) and eventually to cell death (necrosis) 2. Cardiovascular Dysfunctions Reflect Primary Cardiovascular Disturbances or Diseases and are Secondary Consequences of Noncardiovascular Disturbances or Diseases frequent case- Impairment in the transport functions of the cardiovascular system 1. primary cardiovascular dysfunction- more common a. hemorrhage (loss of blood from blood vessels) b. myocarditis- toxic chemical or by a viral or bacterial infection-- inflames the heart muscle and impairs the ability of the heart to pump blood c. congenital (present at birth) or acquired (developing after birth) cardiovascular dysfunction Congenital cardiovascular diseases- involve defective heart valves-- either cannot open fully or cannot close completely 2. Cardiovascular Dysfunctions Reflect Primary Cardiovascular Disturbances or Diseases, But More Often Are Secondary Consequences of Noncardiovascular Disturbances or Diseases Congenital cardiac defects- common in certain breeds of dogs and horses congenital or acquired disease- may be able to pump adequate amount of blood when the animal is at rest, but cannot deliver the increased blood flow required by the body during exercise heart failure-dysfunction in the heart impairs its ability to pump the amount of blood flow normally needed by the body classically exhibits a limited ability or willingness to exercise (exercise intolerance) 2. Cardiovascular Dysfunctions Reflect Primary Cardiovascular Disturbances or Diseases, But More Often Are Secondary Consequences of Noncardiovascular Disturbances or Diseases Parasites are a common cause of acquired cardiovascular dysfunction example: dogs- adult heartworms (Dirofilaria immitis) lodge in the right ventricle and pulmonary artery-- impede the flow of blood release substances into the circulation-- disrupt the body’s ability to control blood pressure and blood flow In horses- bloodworms (Strongylus vulgaris) lodge in the mesenteric arteries and decrease the blood flow to the intestine Impediment of bld flow--result to intestinal ischemia-- digestive functions (motility, secretion, and absorption), and exhibits signs of gastrointestinal distress (colic) 2. Cardiovascular Dysfunctions Reflect Primary Cardiovascular Disturbances or Diseases, But More Often Are Secondary Consequences of Noncardiovascular Disturbances or Diseases 2. secondary cardiovascular dysfunction- cardiovascular system is not the primary target of the disease; serious and life- threatening example: 1. severe burns, persistent vomiting, diarrhea-- leads to loss of water and electrolytes (small, soluble ions in the body fluids; e.g., Na+, Cl–, K+, Ca2+) blood volume is not depleted to low levels but the alteration in electrolyte concentrations can lead to abnormal heart rhythms (cardiac arrhythmias) and ineffective pumping of blood by the heart (heart failure) Use correct fluid therapy incorrect fluid therapy leads to accumulation of excess fluid in the tissues of the body/ “waterlogging” of tissues/ edema-- where excess fluid in the lung tissue (pulmonary edema) slows the flow of oxygen from the pulmonary air sacs (alveoli) into the bloodstream 2. Cardiovascular Dysfunctions Sometimes Reflect Primary Cardiovascular Disturbances or Diseases, But More Often They Are Secondary Consequences of Noncardiovascular Disturbances or Diseases 2. Pulmonary edema is a secondary complication in many disease states. example: shock-lung syndrome, which results when toxic substances in the body trigger an increase in the permeability of the lung blood vessels the “leaky” vessels allow water, electrolytes, plasma proteins, and white blood cells to leave the bloodstream and accumulate in the lung tissue and airways can lead to death 2. Cardiovascular Dysfunctions Reflect Primary Cardiovascular Disturbances or Diseases, But More Often Are Secondary Consequences of Noncardiovascular Disturbances or Diseases 3. other types of shock depress the cardiovascular system: a. Hemorrhagic shock- generalized cardiovascular failure caused by severe blood loss b. Cardiogenic shock- cardiovascular collapse caused by heart failure c. Septic shock- caused by bacterial infections in the bloodstream (bacteremia) d. Endotoxic shock- endotoxins (fragments of bacterial cell walls) enter the bloodstream; this often occurs when the epithelial lining of the intestines becomes damaged 2. Cardiovascular Dysfunctions Reflect Primary Cardiovascular Disturbances or Diseases, But More Often Are Secondary Consequences of Noncardiovascular Disturbances or Diseases pathogenesis of endotoxic shock: bacterial infections-- epithelial damage in the intestines or from ischemia in the intestinal walls (as with bloodworms in horses)--endotoxins enter the bloodstream-- cause the body to produce substances that depress the pumping ability of the heart– results to heart failure---low blood flow and ischemia in all the vital body organs-- Kidney (or renal) failure, respiratory failure, central nervous system (CNS) depression, and death follow. 2. Cardiovascular Dysfunctions Reflect Primary Cardiovascular Disturbances or Diseases, But More Often Are Secondary Consequences of Noncardiovascular Disturbances or Diseases 4. Anesthetic overdose- cause secondary cardiovascular complications depress the CNS--abnormal neural signals to the heart and the blood vessels--depress cardiac output and lower blood pressure barbiturates- depress the pumping ability of the heart directly 3. Substances Transported by the Cardiovascular System Include Nutrients, Waste Products, Hormones, Electrolytes, and Water a. The blood transports the metabolic substrates-- include oxygen, glucose, amino acids, fatty acids, and various lipids. b. The blood also carries away metabolic waste products-- includes carbon dioxide, lactic acid, the nitrogenous wastes of protein metabolism, and heat. c. the heat produced by metabolic processes within cells is transported by the cardiovascular system to the body surface 3. Substances Transported by the Cardiovascular System Include Nutrients, Waste Products, Hormones, Electrolytes, and Water d. also transports vital chemical messengers: the hormones. - synthesized and released by cells in one organ and are carried by the bloodstream to cells in other organs, where they alter organ function. example: 1. insulin--produced by cells of the pancreas-- promotes the cellular uptake of glucose. Inadequate insulin production (as in type 1 diabetes)--inadequate entry of glucose into cells-- glucose concentrations in the blood rise to very high levels low intracellular glucose concentration disrupts to neural functions- lead to diabetic coma 3. Substances Transported by the Cardiovascular System Include Nutrients, Waste Products, Hormones, Electrolytes, and Water 2. adrenaline (epinephrine and norepinephrine)- fr the adrenal medulla- released during periods of stress “fight or flight” response- increase in heart rate and cardiac contractility, dilation of skeletal muscle blood vessels, an increase in blood pressure, increased glycogenolysis, dilation of the pupils and airways, and piloerection (hair standing on end) 3. Substances Transported by the Cardiovascular System Include Nutrients, Waste Products, Hormones, Electrolytes, and Water e. transports water and essential electrolytes- Na+, Cl–, K+, Ca2+, H+, and HCO3– kidneys- responsible for maintaining normal water and electrolyte composition in the body--by altering the electrolyte concentrations in blood as it flows through the kidneys--circulates to all other organs in the body-- normalizes the water and electrolyte content in the extracellular fluids of each tissue 4. Two Modes of Transport Are Used in the Cardiovascular System: Bulk Flow and Diffusion a. bulk flow. rapid over long distances Blood is pumped out of the heart-- travels quickly through the aorta --in 10 seconds it reaches distant parts of the body, including the head and limbs requires energy because of the hydrostatic pressure difference the pressure at one end of a blood vessel is higher than the pressure at the other end for flow to occur perfusion pressure difference/ perfusion pressure- the difference in pressure between two points in a blood vessel 4. Two Modes of Transport Are Used in the Cardiovascular System: Bulk Flow and Diffusion Perfusion- “through-flow,” and the perfusion pressure is the pressure difference that causes blood to flow through blood vessels Effect of the muscular pumping action of the heart -- constitutes the driving force for bulk blood flow through the circulation perfusion pressure difference vs. transmural pressure difference/ transmural pressure) 4. Two Modes of Transport Are Used in the Cardiovascular System: Bulk Flow and Diffusion Transmural means “across the wall,” transmural pressure- difference between the blood pressure inside a blood vessel and the fluid pressure in the tissue immediately outside the vessel (transmural pressure equals inside pressure minus outside pressure) This is the pressure difference that would cause blood to flow out of a vessel if a hole were poked in the vessel wall also called distending pressure, because it corresponds to the net outward “push” on the wall of a blood vessel Fluid pressures associated with a blood vessel. P inlet, P outlet, and P inside- refer to blood pressure within the vessel P outside- refers to the pressure in the tissue fluid (interstitial fluid) immediately outside the blood vessel Perfusion pressure- the pressure difference along the length of a blood vessel Transmural pressure (distending pressure)- the pressure difference across the wall of the vessel, indicated here at the midpoint of the vessel Perfusion pressure is the driving force for blood flow through the vessel, whereas transmural pressure is the driving force that would cause blood to flow out of the vessel if there were a hole in it 4. Two Modes of Transport Are Used in the Cardiovascular System: Bulk Flow and Diffusion b. Diffusion dissolved substances move across the walls of blood vessels, from the bloodstream into the interstitial fluid, or vice versa Interstitial fluid- the extracellular fluid outside capillaries; fluid that bathes each cell of a tissue the movement of substances between the blood and the interstitial fluid takes place across the walls of the capillaries, the smallest blood vessels For a substance (e.g., oxygen) to move from the bloodstream to a tissue cell, it diffuses across the wall of a capillary and into the tissue interstitial fluid, and then diffuses from the interstitial fluid into the tissue cell 4. Two Modes of Transport Are Used in the Cardiovascular System: Bulk Flow and Diffusion The source of energy for diffusion is a concentration difference A substance diffuses from the bloodstream, across the wall of a capillary, and into the interstitial fluid only if the concentration of the substance is higher in the blood than in the interstitial fluid (and if the capillary wall is permeable to the substance) If the concentration of a substance is higher in the interstitial fluid than in the blood, the substance will diffuse from the interstitial fluid into the capillary blood 4. Two Modes of Transport Are Used in the Cardiovascular System: Bulk Flow and Diffusion distinguish diffusion and active transport: a. diffusion- a substance moves passively from an area of high concentration toward an area of low concentration; b. active transport- substances are forced to move in a direction opposite to their concentration gradient substances are not transported actively across the walls of capillaries but the movement of substances between the bloodstream and the interstitial fluid occurs by passive diffusion 5. Diffusion Is Very Slow so Metabolically Active Cell in the Body Must Be Close to a Capillary Carrying Blood by Bulk Flow Inspiration--air containing oxygen (O2) moves by bulk flow through smaller airways (trachea, bronchi, and bronchioles)-- enters the alveolar air sacs (with thin walls separating alveoli contain a meshwork of capillaries)--Blood flowing in alveolar capillaries passes extremely close (within 1 µm) to the air in the alveoli thus, the concentration of oxygen in alveolar capillary blood is lower than the concentration of oxygen in alveolar air---the concentration difference causes some oxygen to diffuse from the alveolar air into the capillary blood Oxygen (O2) is transported from the atmosphere to cells throughout the body by a combination of bulk flow and diffusion. 1. O2 moves by bulk flow through the airways, from the atmosphere to the alveoli (tiny air sacs) of the lungs (inset A). The wall of each alveolus contains a meshwork of alveolar (pulmonary) capillaries (inset B). 2. O2 diffuses from the alveolar air into the blood that is flowing through the alveolar capillaries (inset C). 3. Bulk flow of blood next carries this O2 to the heart; from there it is delivered by bulk flow into the capillaries of all the body organs (except the lungs). 4. In the brain (inset D), skeletal muscle (inset E), and other tissues, O2 moves by diffusion from the capillary blood into the interstitial fluid and then into the tissue cells, where it is utilized to support oxidative metabolism. Bulk flow is rapid- transport O2 to all parts of the body within a few seconds. Diffusion is 5. Diffusion Is Very Slow so Metabolically Active Cell in the Body Must Be Close to a Capillary Carrying Blood by Bulk Flow A large dog- 300 million alveoli- a total surface area of about 130 m2 (equal to half the surface area of a tennis court)-- laced with pulmonary capillaries-- only a tiny amount of oxygen diffuses into each pulmonary capillary but the aggregate uptake of oxygen into the pulmonary bloodstream is substantial (typically, 125 mLO2/minute in a large, resting dog, increasing by a factor of 10 or more during strenuous exercise). both the large alveolar surface area and the proximity of alveolar air to the blood in alveolar capillaries promote efficient diffusion of oxygen; takes less than 1 second for the blood in an alveolar capillary to become oxygenated. 5.Diffusion Is Very Slow so Metabolically Active Cell in the Body Must Be Close to a Capillary Carrying Blood by Bulk Flow As it leaves the lungs, each 100 mL of oxygenated blood normally carries 20 mL of oxygen. About 1.5% of this oxygen is carried in solution; the other 98.5% is bound to the protein hemoglobin within the erythrocytes (red blood cells). The oxygenated blood moves by bulk flow from the lungs to the heart. The heart pumps this oxygenated blood out into the aorta, and from there it is distributed via a complex system of branching arteries to all parts of the body (including the brain and skeletal muscles. Brain: Capillaries in the brain bring a bulk flow of 5.Diffusion Is Very Slow so Metabolically Active Cell in the Body Must Be Close to a Capillary Carrying Blood by Bulk Flow Metabolic processes within the neurons consume oxygen, so the oxygen concentration inside neurons is low. The gradient of oxygen concentration between the capillary blood (high) and the neurons (low) provides the driving force for oxygen to diffuse first from the blood into the interstitial fluid and then into the neurons. Each brain neuron must be within about 100 µm of a capillary carrying blood by bulk flow if diffusion is to deliver oxygen rapidly enough to sustain normal metabolism in the neuron. Difusional exchange over distances up to 100 µm typically takes only 1 to 5 seconds. 5. Diffusion Is Very Slow so Metabolically Active Cell in the Body Must Be Close to a Capillary Carrying Blood by Bulk Flow If the distance involved were a few millimeters, diffusion would take minutes to occur. Diffusion of oxygen a few centimeters through body fluid would take hours. normal life processes require that metabolically active cell of the body be within about 100 µm of a capillary carrying blood by bulk flow If bulk flow is interrupted like a thrombus (blood clot) in the artery, that region of tissue becomes ischemic--leads to dysfunction; persistent, severe ischemia leads to infarction and eventually to necrosis--cerebral infarction leading to stroke 5. Diffusion Is Very Slow soMetabolically Active Cell in the Body Must Be Close to a Capillary Carrying Blood by Bulk Flow Skeletal muscle: capillary carrying bulk flow of blood past a skeletal muscle cell (muscle fiber): Oxygen moves by diffusion from the capillary blood into the muscle interstitial fluid and then into the muscle cell, where it is consumed in the metabolic reactions that provide energy for muscle contraction. The oxygen consumption of a skeletal muscle depends on the severity of its exercise; at a maximum, oxygen consumption may reach levels 40 times greater than the resting level. skeletal muscle has tremendous metabolic capacity so have high density of capillaries--- this provides more surface area for diffusional exchange and brings the bulk flow of blood extremely close to all parts of each skeletal muscle cell. 5. Diffusion Is Very Slow so Metabolically Active Cell in the Body Must Be Close to a Capillary Carrying Blood by Bulk Flow Heart muscle: consumes a large amount of oxygen. Oxygenated blood is carried from the aorta to the heart muscle by a network of branching coronary arteries---this blood moves by bulk flow into coronary capillaries, which pass close by each cardiac muscle cell. a thrombus interrupts the bulk flow of blood in a coronary artery, the heart muscle cells supplied by that artery become ischemic (the cardiac muscle deprived of blood flow lies within a few millimeters of the left ventricular chamber, which is filled with oxygen-rich blood)---Oxygen cannot diffuse rapidly enough from the ventricular chamber to the ischemic cells to sustain their metabolism. Ischemic cardiac muscle loses its ability to contract forcefully; cardiac arrhythmias may develop; severe myocardial ischemia--- myocardial infarction, or heart attack. 5.Diffusion Is Very Slow so Metabolically Active Cell in the Body Must Be Close to a Capillary Carrying Blood by Bulk Flow Coronary artery disease and cerebrovascular disease are encountered more often in human medicine than in veterinary medicine. cardiac disease (dysfunction of the heart muscle or valves, as distinguished from disease of the coronary arteries) is encountered more often in veterinary medicine than in human medicine. 6. The Pulmonary and Systemic Circulations Are Arranged In Series, But the Various Organs Within the Systemic Circulation Are Arranged in Parallel blood is pumped from the left ventricle into the aorta. The aorta divides and subdivides to form many arteries--- deliver fresh, oxygenated blood to each organ of the body, except the lungs. The pattern of arterial branching that delivers blood of the same composition to each organ is called parallel. After blood passes through the capillaries within individual organs, it enters veins---small veins combine to form progressively larger veins, until the entire blood flow is delivered to the right atrium by way of the venae cavae (pleural of vena cava,includes both superior vena cava and inferior vena cava) The blood vessels between the aorta and the venae cavae (including the blood vessels in all organs of the body except the lungs) are collectively called the systemic circulation. General layout of the cardiovascular system, showing that the systemic and pulmonary circulations are arranged in series and that the organs within the systemic circulation are arranged in parallel. LA, Left atrium; LV, left ventricle; PA, pulmonary artery; PV, pulmonary vein; RA, right atrium; RV, right ventricle. Oxygenated blood has a bright red color; deoxygenated blood is darker and bluish red. The drawing also shows that, if an open tube containing mercury (black) were stuck into the aorta, the normal blood pressure within the aorta would push mercury nearly 100 mm upward into the tube, at which point the upward force of the blood pressure would be equalized by the downward force of gravity acting on the mercury. In contrast, the blood pressure in the venae cavaeis much lower (typically about 3 mm Hg), as illustrated on the left side of the drawing. (Modified 6. The Pulmonary and Systemic Circulations Are Arranged In Series, But the Various Organs Within the Systemic Circulation Are Arranged in Parallel From the right atrium, blood passes into the right ventricle, which pumps it into the pulmonary artery. The pulmonary artery branches into progresively smaller arteries, which deliver blood to each alveolar (pulmonary) capillary. Blood from pulmonary capillaries is collected in pulmonary veins and brought to the left atrium. Blood then passes into the left ventricle, completing the circuit. The blood vessels of the lungs, including the pulmonary arteries and veins, constitute the pulmonary circulation. The pulmonary circulation and the heart are collectively termed the central circulation. 6. The Pulmonary and Systemic Circulations Are Arranged In Series, But the Various Organs Within the Systemic Circulation Are Arranged in Parallel The pulmonary circulation and the systemic circulation are arranged in series; that is, blood must pass through the pulmonary vessels between each passage through the systemic circuit. In one pass through the systemic circulation, blood generally encounters only one capillary bed before being collected in veins and returned to the heart, although a few exceptions to this rule exist. One exception occurs in the splanchnic circulation, which supplies blood to the digestive organs--- blood that leaves the gastric, splenic, or mesenteric capillaries enters the portal vein. The portal vein carries splanchnic venous blood to the liver, where the blood passes through another set of capillaries before it returns to the heart. This arrangement of two systemic capillary beds in series is called a portal system. 6. The Pulmonary and Systemic Circulations Are Arranged In Series, But the Various Organs Within the Systemic Circulation Are Arranged in Parallel a. The splanchnic portal system allows nutrients that have been absorbed from the gastrointestinal tract to be delivered directly to the liver---the nutrients are transformed for storage or allowed to pass into the general circulation. The liver also receives some blood directly from the aorta through the hepatic artery. b. The kidneys also contain a portal system---blood enters a kidney by way of a renal artery and passes through two sets of capillaries (called glomerular and tubular) before returning to the venous side of the systemic circulation Large amounts of water, electrolytes, and other solutes are filtered out of the blood as it passes through the glomerular capillaries. 6. The Pulmonary and Systemic Circulations Are Arranged In Series, But the Various Organs Within the Systemic Circulation Are Arranged in Parallel Most of this filtered material is reabsorbed into the bloodstream as it flows through the peritubular capillaries. The remainder becomes urine. The kidneys use the renal portal system to adjust the amounts of water, electrolytes, and other critical solutes in the blood. c. A third portal system is found in the brain; important in the control of hormone secretion by the pituitary gland. After traversing capillaries in the hypothalamus, blood enters portal vessels that carry it to the anterior pituitary gland (adenohypophysis) and to another set of capillaries 6. The Pulmonary and Systemic Circulations Are Arranged In Series, But the Various Organs Within the Systemic Circulation Are Arranged in Parallel As blood traverses the hypothalamic capillaries, it picks up several signaling chemicals that control the release of pituitary hormones. When this blood reaches capillaries in the anterior pituitary gland, these substances diffuse out of the bloodstream and into the pituitary interstitial fluid, where they act on pituitary cells to increase or decrease their secretion of specific pituitary hormones. This system is called the hypothalamic-hypophyseal portal system. To summarize, except for a few specialized portal systems, blood encounters only one capillary bed in a single pass through the systemic circulation. 7. Cardiac Output Is the Volume of Blood Pumped Each Minute by One Ventricle In a resting dog, it takes about 1 minute for blood to traverse the entire circulation (from the left ventricle back to the left ventricle). Because the pulmonary and systemic circulations are in series, the volume of blood pumped by the right side of the heart each minute must equal the volume of blood pumped by the left side of the heart each minute. The volume of blood pumped per minute by either the left ventricle or the right ventricle is called cardiac output. cardiac output at rest is approximately 3 liters per minute per square meter (L/min/m2) of body surface area. 7. Cardiac Output Is the Volume of Blood Pumped Each Minute by One Ventricle A large dog (e.g., German shepherd) typically has a body surface area a little less than 1 m2 and a cardiac output at rest of about 2.5 L/min. In an animal at rest, blood entering the aorta is divided: 20% of it flows through the splanchnic circulation, 20% through the kidneys, 20% goes to the skeletal muscles, 15% goes to the brain and the coronary arteries carry about 3% of the cardiac output. The remainder goes to skin and bone. 8. The Perfusion Pressure for the Systemic Circulation Is Much Greater Than the Perfusion Pressure for the Pulmonary Circulation When the left ventricle contracts and ejects blood into the aorta, the aorta becomes distended with blood, and aortic blood pressure rises to a peak value called systolic pressure (typically 120 mm Hg). Between ejections, blood continues to flow out of the aorta into the downstream arteries. This outflow of blood from the aorta causes aortic pressure to decrease. The minimal value of aortic blood pressure, just before the next cardiac ejection, is called diastolic pressure (typically 80 mm Hg). The mean aortic pressure (average value of the pulsatile blood pressure in the aorta) is about 98 mm Hg. 8. The Perfusion Pressure for the Systemic Circulation Is Much Greater Than the Perfusion Pressure for the Pulmonary Circulation means that, if an open tube containing mercury were stuck into the aorta, the blood pressure within the aorta would push mercury 98 mm upward into the tube; the upward force of the blood pressure would be equalized by the downward force of gravity acting on the mercury The mean aortic pressure represents a potential energy for driving blood through the systemic circulation. As blood flows through the systemic blood vessels, this pressure energy is dissipated through friction. The potential energy (blood pressure) remaining by the time the blood reaches the venae cavae is only 3 mm Hg. Therefore the perfusion pressure for the systemic circuit is typically 98 mm Hg minus 3 mm Hg, or 95 mm Hg. 8. The Perfusion Pressure for the Systemic Circulation Is Much Greater Than the Perfusion Pressure for the Pulmonary Circulation Right ventricular contractions cause pulsatile ejections of blood into the pulmonary artery. The pulsatile variations in pulmonary arterial blood pressure typically have a peak (systolic) value of 20 mm Hg and a minimum (diastolic) value of 8 mm Hg. The typical value for mean pulmonary artery blood pressure is 13 mm Hg. The blood pressure in pulmonary veins (at the point where they enter the left atrium) is typically 5 mm Hg. Under these conditions the perfusion pressure for blood flow through the lungs is 8 mm Hg (i.e., 13 mm Hg minus 5 mm Hg). The same volume of blood (the cardiac output) flows each minute through the systemic circulation and through the lungs; from the typical values, the perfusion pressure for the systemic circuit is much 8. The Perfusion Pressure for the Systemic Circulation Is Much Greater Than the Perfusion Pressure for the Pulmonary Circulation this difference in perfusion pressure is because the systemic vessels offer more friction against blood flow (i.e., have a higher resistance) than do the pulmonary vessels. Therefore the systemic circulation is referred to as the high-pressure, high-resistance side of the circulation. The pulmonary circuit is called the low-pressure, low- resistance side. By convention, blood pressures are always measured with reference to atmospheric pressure. Thus an aortic pressure of 98 mm Hg means that the blood pressure in the aorta is 98 mm Hg higher than the atmospheric pressure outside the body. 8. The Perfusion Pressure for the Systemic Circulation Is Much Greater Than the Perfusion Pressure for the Pulmonary Circulation blood pressure is also measured at heart level---blood pressure cuffs are applied over the brachial artery (in the upper arm); the brachial artery is at the same level as the heart. If blood pressure is measured in an artery or vein at a level different from heart level, an arithmetic correction should be made so that the pressure is reported as if it had been measured at heart level. This correction is necessary because gravity pulls downward on blood and therefore affects the actual pressure of blood within vessels. Gravity increases the actual blood pressure in vessels lying below heart level and decreases the actual pressure in vessels above heart level. The gravitational effect is significant in an animal the size of a dog and substantial in an animal the size of a horse. The correction factor for the effect of gravity is 1 mm Hg for each 1.36 cm above or below heart level. 9. Each Type of Blood Vessel Has Physical Properties Suited to Its Particular Function In a resting animal, at any one moment, about 25% of the blood volume is in the central circulation and about 75% is in the systemic circulation Most of the blood in the systemic circulation is found in the veins; 20% of the systemic blood is found in the arteries, arterioles, and capillaries. systemic veins are known as the blood reservoirs of the circulation. Arteries function as high-pressure conduits for rapid distribution of blood to the various organs. Arterioles are the “gates” of the systemic circulation; they constrict or dilate to control the bloodflow to each capillary bed. a small fraction of the systemic blood is found in capillaries at any one time, it is within these exchange vessels that the important diffusional transport takes place between the bloodstream and the interstitial fluid. Distribution of Blood Volume in the Cardiovascular System of a Normal Dog Geometry of Systemic Circulation of a 30-kg Resting Dog 9. Each Type of Blood Vessel Has Physical Properties Suited to Its Particular Function As the aorta branches into smaller vessels, the diameters of the vessels become smaller, but the number of vessels increases. One aorta supplies blood to 45,000 terminal arteries, each of which gives rise to more than 400 arterioles. Each arteriole typically branches into about 80 capillaries. The capillaries are so small in diameter that red blood cells must pass through in single file. the total cross-sectional area of the capillaries is much greater than the cross-sectional area of the preceding arteries and arterioles. Because capillary blood flow is spread out over such a large cross-sectional area, the flow velocity within capillaries is low. 9. Each Type of Blood Vessel Has Physical Properties Suited to Its Particular Function Blood moves rapidly (about 13 cm/sec) through the aorta and large arteries. At this speed, blood is delivered from the heart to all parts of the body in less than 10 seconds. The velocity of blood flow decreases as the blood leaves arteries and enters arterioles and capillaries in each tissue. The velocity of blood flow in capillaries is so slow that blood typically takes about 1 second to travel the 0.5 mm length of a capillary where the diffusional exchange takes place between the capillary blood and the interstitial fluid. Blood from the capillaries is collected by venules and veins and is carried quite rapidly back to the heart. 9. Each Type of Blood Vessel Has Physical Properties Suited to Its Particular Function the normal dynamics of blood flow provides a basis for interpretation of capillary refill time, which is measured during a typical clinical physical examination. locate an area of non-pigmented epithelial membrane (most commonly a non-pigmented area of the gums)---normally pink, due to an adequate flow of well-oxygenated blood through the small vessels (arterioles, capillaries, and venules)--- apply firm finger pressure to the area for 1 or 2 seconds, which compresses all the small blood vessels and squeezes the blood out of them---upon release of the finger pressure, the tissue appears very pale, due to the absence of blood in the small vessels. A normal circulation will restore blood flow through the small vessels and the pink color will return within 1 to 2 seconds (the normal capillary refill time). A prolonged capillary refill time is indicative of poor perfusion of the tissue and, by inference, a sluggish circulation. 9. Each Type of Blood Vessel Has Physical Properties Suited to Its Particular Function know the branching pattern of the systemic vessels to graph the velocity of blood flow within the different types of vessels. emphasize the rapidity of bulk flow through large vessels and the relatively slow flow through the capillaries. the velocity of blood flow is lowest in the capillaries; however, the same volume of blood necessarily flows each minute through an artery, the capillaries that it feeds, and the veins draining the capillaries. based on x-sectional area: a large cross-sectional area (and therefore slow velocity of blood flow), capillaries have a large surface area. The total surface area of the walls of all the capillaries in the systemic circulation of a large dog is about 20 m2, which is nearly 30 times greater than the dog’s body surface area. The large surface area of capillaries helps promote efficient diffusional exchange between the capillary blood and the interstitial fluid. As blood from the capillaries is collected into venules and veins, the total cross-sectional area is As the systemic arteries branch to form small reduced, so the velocity of blood flow increases arteries, arterioles, and capillaries (A), the again. Therefore, blood moves quickly from the total cross-sectional area of the vessels heart to the microvessels, where it stays for a few increases, so the forward velocity of blood seconds before moving rapidly back to the heart. flow decreases 10. Blood Is a Suspension of Cells in Extracellular Fluid (Plasma) blood can be separated into its cellular and liquid components by centrifugation. plasma- the liquid phase of blood; lighter in weight than the cells; ends up on the top of the centrifuge tube. is acellular; or extracellular liquid in blood constitution: a. water- 93% of the plasma volume; b. 5% to 7%- protein molecules- gives plasma its typical pale-yellow color. synthesized in the liver and are added to the bloodstream as it passes through the liver capillaries. Globulin, albumin, and fibrinogen are the primary plasma 10. Blood Is a Suspension of Cells in Extracellular Fluid (Plasma) Globulin, albumin, and fibrinogen are the primary plasma proteins. Globulin and albumin-important in immune responses Fibrinogen- important in the process of blood clotting. If blood is removed from the body and allowed to stand for a few moments, the soluble fibrinogen molecules polymerize to form an insoluble matrix of fibrin. This causes the blood to congeal, or coagulate. Coagulation can be prevented by adding an anticoagulant to the blood; the most common anticoagulants are heparin and citrate. An anticoagulant must be added in preparation for separating blood into its cellular and plasma fractions by centrifugation Anticoagulated blood can be separated into an extracellular fluid component (plasma) and a cellular component (cells) by centrifugation. Plasma is a solution of many important substances in water. The presence of proteins gives plasma its typical pale-yellow color. The cells are heavier than the plasma, and they settle to the bottom. Most of the cells are red blood cells. The white blood cells are slightly lighter in weight than the red blood cells, and they form a thin buffy coat on the top of the red cell layer. Most of the platelets end up in the buffy coat, although at slow centrifuge speeds (“soft spin”), platelets tend to remain suspended in the plasma. The fraction of cells in blood is called the hematocrit. In this example the hematocrit is 45%. 10. Blood Is a Suspension of Cells in Extracellular Fluid (Plasma) c. ions (electrolytes) a. Na+- the dominant cation b.Cl- and bicarbonate (HCO3)-the predominant anions c. other ions The concentration of each plasma electrolyte-kept within narrow limits for body function to be normal, and numerous control systems accomplish this regulation. the plasma electrolytes diffuse readily across capillary walls; therefore, interstitial fluid and plasma typically have similar electrolyte concentrations 10. Blood Is a Suspension of Cells in Extracellular Fluid (Plasma) d. small amounts of gases (O2, CO2, and N2) in solution. 1. O2- In the lungs, O2 enters the blood as dissolved O2, but most of this O2 quickly combines with hemoglobin (in the redblood cells). about 98.5% of the total O2 in blood is carried as oxyhemoglobin and only about 1.5% as disolved O2. 2. CO2- only a small portion is carried in the dissolved form in the blood Most becomes hydrated to form HCO3– or combines with hemoglobin or plasma proteins to form carbamino compounds. e. Nutrient substances- glucose, amino acids, lipids, and some vitamins. f. Dissolved metabolic waste products (in addition to CO2) include urea, creatinine, uric acid, and bilirubin. g. hormones (e.g., insulin, epinephrine, thyroxine)- tiny, but critically important amounts. Some Constituents of Canine Plasma (in Addition to Water, the Main Constituent) 11. The Cellular Component of Blood Includes Red Blood Cells, White Blood Cells, and Platelets Cells normally constitute 30% to 60% of the blood volume (depending on the species). The fraction of cells in blood is called the hematocrit The hematocrit is determined by adding an anticoagulant to some blood and then centrifuging it in a tube. The cells are somewhat heavier than plasma and settle to the bottom of the tube during centrifugation. centrifugation results in a packing of the blood cells in the bottom of the tube, the hematocrit is sometimes called the packed cell volume. a. erythrocytes- acquire their red color from hemoglobin 11. The Cellular Component of Blood Includes Red Blood Cells, White Blood Cells, and Platelets b. leukocytes (white blood cells, WBCs)- slightly lighter in weight than the RBCs; in a centrifuge tube the WBCs gather in a white buffy coat on top of the RBCs. buffy coat- normally very thin because there are about 1000 times more RBCs than WBCs. critical in immune and allergic responses of the body. The subtypes: neutrophils, lymphocytes, monocytes, eosinophils, and basophils. A laboratory analysis of the total number and relative distribution of the various WBC subtypes (differential WBC count) provides important clues in the diagnosis of disease. erythrocytes and leukocytes are made in the bone marrow--- develop, by mitosis and differentiation, from a common line of progenitor cells, the pluripotent (uncommitted) stem cells. 11. The Cellular Component of Blood Includes Red Blood Cells, White Blood Cells, and Platelets c. thrombocytes- or platelets, or thrombocytes; cellular fragments from their precursor cells, the megakaryocytes. The megakaryocytes reside in the bone marrow, and they shed bits of their cytoplasm, bounded by cell membrane, into the bloodstream. Platelets participate in hemostasis (the control of blood loss from injured or severed blood vessels-- process of clumping together of platelets (platelet aggregation) begins to create a physical barrier across openings in blood vessels. also release the substance serotonin, which causes the blood vessels to constrict, thereby reducing blood pressure and blood flow at the site of injury. substances released from the platelets, along with fibrinogen and several clotting factors in the plasma, lead to the coagulation of blood and the formation of a stable, fibrin-based blood clot 11. The Cellular Component of Blood Includes Red Blood Cells, White Blood Cells, and Platelets Coagulation and clotting- a complex, interconnected sequences of chemical reactions (the coagulation cascade). A key step in the coagulation cascade is the formation in the plasma of thrombin, an enzyme that catalyzes the transformation of fibrinogen to fibrin. laboratory tests to assess the status of an animal’s coagulation system-- determination of the prothrombin time (PT) and the partial thromboplastin time (PTT). If blood is allowed to coagulate and then is centrifuged, the fibrin and other plasma clotting factors settle to the bottom along with the RBCs, WBCs, and platelets. The liquid portion remaining above (essentially plasma without fibrinogen and other clotting factors) is called serum. Most of the common clinical blood chemistry analyses are performed on serum. Examples include the determination of concentrations of electrolytes and cholesterol. 11. The Cellular Component of Blood Includes Red Blood Cells, White Blood Cells, and Platelets If blood is treated with an anticoagulant and then allowed simply to sit in a tube (without centrifugation), the erythrocytes slowly begin to settle- erythrocyte sedimentation rate (ESR) the rate of their settling tends to be increased to above normal in certain disease states and decreased to below normal in others. the normal ESR varies between species; for example, it is much more rapid in equine blood than in canine blood. Blood cell counts are performed by manual or automated scanning of a very small volume (e.g., 1 µL) of anticoagulated whole blood. Canine Hematology 12. Most of the Oxygen in Blood Is Carried in Chemical Combination with the Protein Hemoglobin Within Red Blood Cells Of the 20 mL of O2 normally carried in each 100 mL of oxygenated blood, only 1.5% (0.3 mL) is carried in dissolved form. The remaining 98.5% is carried in chemical combination with hemoglobin (in RBCs). Oxygenated hemoglobin (oxyhemoglobin, HbO2) is bright red. When O2 is released, HbO2 becomes reduced hemoglobin (Hb), which is dark bluish red. The adequacy of oxygenation of an animal’s blood- check color of its nonpigmented epithelial membranes (e.g., gums, nostrils, or inside surfaces of eyelids). Well-oxygenated tissues appear pink. Poorly oxygenated tissues appear bluish (cyanotic)because of the prevalence of reduced Hb. 12. Most of the Oxygen in Blood Is Carried in Chemical Combination with the Protein Hemoglobin Within Red Blood Cells The ability of blood to carry oxygen is determined by the amount of hemoglobin in the blood and by the chemical characteristics of that Hb. For example, each deciliter (dL) of normal dog blood contains about 15 g of Hb. Each gram of Hb can combine with 1.34 mL of O2, when fully saturated. Thus, each deciliter of fully oxygenated, normal blood carries 20 mL of O2. Several disease states (hemoglobinopathies) result in the synthesis of chemically abnormal Hb, with a diminished capacity to bind O2. several common toxins, including carbon monoxide (CO) 12. Most of the Oxygen in Blood Is Carried in Chemical Combination with the Protein Hemoglobin Within Red Blood Cells hemoglobin is localized inside RBCs--can get clinically useful relationships among the blood Hb content, RBC count, Hb content of each RBC, and hematocrit. For example, if a normal dog has 15 g of Hb in each deciliter of blood and an RBC count of 6 million cells per microliter (µL) blood, it follows that each RBC (on average) contains 25 picograms (pg) of Hb: The value calculated in this way is called the mean corpuscular hemoglobin (MCH). 12. Most of the Oxygen in Blood Is Carried in Chemical Combination with the Protein Hemoglobin Within Red Blood Cells An easier calculation, which serves the same purpose, is to determine how much hemoglobin is contained in each deciliter of packed RBCs. For example, if a dog has 15 g Hb/dL of blood and has a hematocrit of 50%, the Hb concentration in the RBC portion of the blood must be 30 g of Hb/dL of packed RBCs: The value calculated in this way is called the mean corpuscular hemoglobin concentration (MCHC). For simplicity, the calculation is often summarized as follows: MCHC= hemoglobin /hematocrit 12. Most of the Oxygen in Blood Is Carried in Chemical Combination with the Protein Hemoglobin Within Red Blood Cells The brackets around “hemoglobin” denote concentration. An abnormally low value of MCH or MCHC is clinically important- points to a deficit in hemoglobin synthesis (i.e., not enough Hb being made to load up each RBC). an abnormally low value for Hb by itself is less informative; hemoglobin concentration in the blood could fall below normal for several reasons, including a deficit in Hb synthesis, a deficit in RBC synthesis, or a “watering down” of the blood either by addition of excess plasma fluid or by loss of RBCs. Deviations from a normal hematocrit (Hct) have important consequences in the ability of blood to carry oxygen. 12. Most of the Oxygen in Blood Is Carried in Chemical Combination with the Protein Hemoglobin Within Red Blood Cells Hematocrit also affects the viscosity of blood Viscosity- measure of resistance to flow; example, honey is more viscous (more resistant to flow) than water. Plasma is about 1.5 times more viscous than water because of the presence of plasma protein molecules (albumin, globulin, fibrinogen). The presence of cells in blood has an even greater effect on viscosity. Blood with an Hct of 40% has twice the viscosity of plasma. 12. Most of the Oxygen in Blood Is Carried in Chemical Combination with the Protein Hemoglobin Within Red Blood Cells An abnormally high hematocrit is called polycythemia, which literally means “many cells in the blood.” The blood of a patient with polycythemia can carry more than the normal 20 mL of O2/dL of blood (provided that the MCHC is normal), and this may be viewed as beneficial. the increased viscosity makes it difficult for the heart to pump the blood. polycythemia creates a heavy workload for the heart and can lead to heart failure, particularly if the cardiac muscle is not healthy anemia- hematocrit is too low Anemia literally means “no blood,”; abnormally few RBCs in each dL or a condition with abnormally low hemoglobin concentration in each RBC (i.e., MCH and/or MCHC is low). Plasma is more viscous than water because of the presence of plasma proteins. Blood is more viscous than plasma because of the presence of blood cells. Blood viscosity increases sharply when the fraction of cells (hematocrit) increases above 50%. Relative size and shape of the major constituents of blood. The figure emphasizes two points: first, that the plasma protein molecules are huge compared with the other plasma solutes, such as glucose, Na+, and Cl–; and second, that the blood cells (red and white) are huge compared with plasma protein molecules. Numbers under constituents are their molecular weights (in daltons). The scale (upper left) indicates a length of 10 nm. In comparison, the diameter of the red blood 12. Most of the Oxygen in Blood Is Carried in Chemical Combination with the Protein Hemoglobin Within Red Blood Cells Each deciliter of blood of an anemic patient carries less than the normal 20 mL of O2. Therefore, cardiac output must be increased above normal to deliver the normal amount of O2 to the tissues each minute. The necessity to increase cardiac output also imposes an increased workload on the heart and can lead to the failure of a diseased heart. Thus, Hct within the normal range provides the blood with enough Hb to carry an adequate amount of O2 without putting an undue workload on the heart. The plasma proteins are much, much larger than the ions and nutrient molecules that are dissolved in plasma. RBCs and WBCs are many, many times larger than the plasma proteins. In fact, as mentioned earlier, blood cells are so large Electrical Activity of the Heart KEY POINTS 1. Contraction of cardiac muscle cells is triggered by an electrical action potential. 2. The contractile machinery in cardiac muscle is similar to that in skeletal muscle. 3. Cardiac muscle forms a functional syncytium. 4. Cardiac contractions are initiated by action potentials that arise spontaneously in specialized pacemaker cells. 5. A system of specialized cardiac muscle cells initiates and organizes each heartbeat. 6. Cardiac action potentials are extremely long. 7. Membrane calcium channels play a special role in cardiac muscle. Electrical Activity of the Heart 8. The long duration of the cardiac action potential guarantees a period of relaxation (and refilling) between heartbeats. 9. Atrial cells have shorter action potentials than ventricular cells. 10. Specialized ion channels cause cardiac pacemaker cells to depolarize to threshold and form action potentials. 11. Sympathetic and parasympathetic nerves act on cardiac pacemaker cells to increase or decrease the heart rate. 12. Cells of the atrioventricular node act as auxiliary pacemakers and protect the ventricles from beating too fast. 13. Sympathetic nerves act on all cardiac muscle cells to cause quicker, more forceful contractions. Electrical Activity of the Heart 14. Parasympathetic effects are opposite to those of sympathetic activation but are generally restricted to the sinoatrial node, atrioventricular node, and atria. 15. Dysfunction in the specialized conducting system leads to abnormalities in cardiac rhythm (arrhythmias). 16. Atrioventricular node block is a common cause of cardiac arrhythmias. 17. Cardiac tachyarrhythmias result either from abnormal action potential formation (by the sinoatrial node or ectopic pacemakers) or from abnormal action potential conduction (“reentry”). 18. Common antiarrhythmic drugs affect the ion channels responsible for the cardiac action potential. 1. Contraction of Cardiac Muscle Cells Is Triggered by an Electrical Action Potential The heart is a muscular pump that propels blood through the blood vessels by alternately relaxing and contracting. As the heart muscle relaxes, the atria and ventricles fill with venous blood. During cardiac contraction, some of this blood is ejected into the arteries. Cardiac contraction takes place in two stages: (1) the right and left atria begin to contract, and (2) after a delay of 50 to 150 milliseconds (msec), the right and left ventricles begin to contract. Atrial contraction helps to finish filling the ventricles with blood. 1. Contraction of Cardiac Muscle Cells Is Triggered by an Electrical Action Potential Ventricular contraction ejects blood out of the left ventricle into the aorta and out of the right ventricle into the pulmonary artery. After the atria and ventricles contract, they relax and begin to refill. The entire contractile sequence is initiated and organized by an electrical signal, an action potential, which propagates from muscle cell to muscle cell, through the heart. discuss cardiac muscle contraction and description of the action potentials that initiate and organize the heart’s contractions. comparison between cardiac and skeletal muscle: 1. In both cardiac and skeletal muscle, an electrical action potential in each muscle cell is necessary to trigger a contraction. 2. The molecular mechanisms that carry out the contraction are also similar in both types of muscle. 1. Contraction of Cardiac Muscle Cells Is Triggered by an Electrical Action Potential 3. difference in the characteristics of the action potentials that initiate contractions. Cardiac muscle, like skeletal muscle, has a striated appearance under the light microscope These cross-striations have the same structural basis in cardiac muscle as in skeletal muscle Each striated cardiac muscle cell (muscle fiber) is made up of a few hundred myofibrils. Each myofibril has a repetitive pattern of light and dark bands. The various bands within a myofibril are given letter designations (A band, I band, Z disk). Sequence of Events in Contraction of Skeletal Muscle and Cardiac Muscle 2. The Contractile Machinery in Cardiac Muscle Is Similar to That in Skeletal Muscle The alignment of these bands in adjacent myofibrils accounts for the striated appearance of the whole muscle fiber. Each repeating unit of myofibrillar bands is called a sarcomere. sarcomere means “little muscle,”; a single sarcomere constitutes the contractile subunit of the cardiac muscle; extends from one Z disk to the next, a distance of approximately 0.1 mm, or 100 µm. each muscle sarcomere is composed of an array of thick and thin filaments. The thin filaments are attached to the Z disks; they interdigitate with the thick filaments. 2. The Contractile Machinery in Cardiac Muscle Is Similar to That in Skeletal Muscle The thin filaments are composed of actin molecules. The thick filaments are composed of myosin molecules. In the presence of adenosine triphosphate (ATP) and calcium ions (Ca2+), myosin and actin interact in a series of steps called the cross-bridge cycle,which results in contraction and force generation in each sarcomere and therefore in the whole muscle cell 4. they differ in electrical linkages between neighboring cells, and this has important consequences. Individual skeletal muscle cells are electrically isolated (insulated) from one another, so action potentials cannot “jump” from one skeletal muscle cell to another. Under the light microscope, cardiac muscle fibers (muscle cells) are seen to be striated, similar to skeletal muscle. Electron microscopy reveals that the striations result from an orderly arrangement of actin (thin) filaments and myosin (thick) filaments into muscular subunits called sarcomeres (as shown in bottom drawing). Like skeletal muscle, a sarcomere is the structural and functional subunit of cardiac muscle. Unlike skeletal muscle fibers, however, cardiac muscle fibers often branch, and they link end to end with neighboring fibers at structures called intercalated disks. Unseen within the intercalated disks are nexi, or gap junctions,which are minute 3. Cardiac Muscle Forms a Functional Syncytium an action potential in a skeletal muscle cell is initiated only in response to an action potential in the somatic motor neuron that innervates the skeletal muscle cell. Each neural action potential causes release of acetylcholine, which activates nicotinic cholinergic receptors on the skeletal muscle cell, which in turn depolarizes the muscle cell to threshold for the formation of an action potential. When formed, the action potential propagates along the length of that particular muscle cell and then stops. The muscle action potential causes the cell to contract. Neighboring cells may or may not contract at the same time, depending on whether action potentials are initiated in the neighboring cells by their motor neurons. 3. Cardiac Muscle Forms a Functional Syncytium In contrast, cardiac muscle cells are electrically linked to one another. When an action potential is started in a single cardiac muscle cell, it propagates along the length of that cell. At specialized points of contact with neighboring cells, ionic currents created by the action potential flow into the neighboring cells and initiate action potentials in those cells, too. Because cardiac action potentials propagate from cell to cell through cardiac tissue, neighboring cardiac muscle cells all contract in synchrony, as a unit, and then they all relax. In this regard, cardiac muscle tissue behaves as if it were a single cell. Cardiac muscle form a functional syncytium (literally, “acts like same cell”). 3. Cardiac Muscle Forms a Functional Syncytium The specialized cellular structures that allow cardiac action potentials to propagate from cell to cell are evident under the light microscope Cardiac muscle appears as an array of fibers (individual cardiac muscle cells) that are arranged approximately in parallel but with some branching. Adjacent cells are joined together by dark-appearing structures called intercalated disks. Electron microscopy show that within these disks are tiny open channels between neighboring cells. These nexi, or gap junctions, provide points of contact between the intracellular fluid of adjacent cells. 3. Cardiac Muscle Forms a Functional Syncytium When an action potential depolarizes the cell on one side of an intercalated disk, positive ions flow through the gap junctions and into the neighboring cell. This local, ionic current depolarizes the neighboring cell to threshold for the formation of an action potential. In effect, an action potential propagates from cell to cell through the gap junctions that are located within the intercalated disks. Skeletal muscle does not have intercalated disks or nexi (gap junctions). 4. Cardiac Contractions Are Initiated by Action Potentials That Arise Spontaneously in Specialized Pacemaker Cells since cardiac muscle tissue forms a functional syncytium, and since a cardiac action potential leads to contraction, any one cardiac muscle cell can initiate a heartbeat. if a single cardiac muscle cell depolarizes to threshold and forms an action potential, that action potential will propagate from cell to cell, throughout the heart, and cause the whole heart to contract. cardiac muscle cells have the property of remaining stable at a resting membrane potential; they never form action potentials by themselves. a few specialized cardiac muscle cells have the property of depolarizing spontaneously toward the 4. Cardiac Contractions Are Initiated by Action Potentials That Arise Spontaneously in Specialized Pacemaker Cells Cardiac cells that depolarize spontaneously toward threshold are called pacemaker cells because they initiate heartbeats and therefore determine the rate, or pace, of the heart. Although all spontaneously depolarizing cells in the heart are called pacemaker cells, only one pacemaker cell, the one that reaches threshold first, actually triggers a particular heartbeat. In the normal heart, the pacemaker cells that depolarize most quickly to threshold are located in the sinoatrial (SA) node. The SA node is in the right atrial wall, at the point where the venae cavae enter the right atrium. 4. Cardiac Contractions Are Initiated by Action Potentials That Arise Spontaneously in Specialized Pacemaker Cells Because it has spontaneously depolarizing pacemaker cells, the heart initiates its own muscle action potentials and contractions. Motor neurons are not necessary for initiating cardiac contractions, but needed for initiating skeletal muscle contractions. Motor neurons (sympathetic and parasympathetic) can affect the heart rate, by influencing the rapidity with which the pacemaker cells depolarize to threshold, but the pacemaker cells initiate action potentials, and therefore heartbeats, even without any sympathetic or parasympathetic influences. Thus a denervated heart still beats, whereas a denervated skeletal muscle remains relaxed (in fact, paralyzed). The ability of the heart to beat without neural input enables surgically transplanted hearts to function. 4. Cardiac Contractions Are Initiated by Action Potentials That Arise Spontaneously in Specialized Pacemaker Cells When a donor’s heart is connected to a recipient’s circulation during cardiac transplantation, no nerves (S and PS) are attached to the transplanted heart. The pacemaker cells in the transplanted heart initiate its action potentials and contractions. Each normal heartbeat is initiated by an action potential that arises spontaneously in one of the pacemaker cells in the SA node When formed, the action potential propagates rapidly, from cell to cell, across the right and left atria, causing both atria to contract. the action potential propagates slowly, from cell to cell, through a special pathway of cardiac muscle cells that lies between the atria and the ventricles. 5. A System of Specialized Cardiac Muscle Cells Initiates and Organizes Each Heartbeat This pathway consists of the atrioventricular (AV) node and the first part of the AV bundle, also called the bundle of His. The AV node and AV bundle provide the only route for the propagation of action potentials from the atria to the ventricles. the atria and ventricles are separated by a layer of connective tissue, which can neither form nor propagate action potentials. the AV node and the first part of the AV bundle also have the special property of very slow conduction of action potentials. It takes 50 to 150 msec for an atrial action potential to travel through the AV node and the first part of the AV bundle or it takes 50 to 150 msec for an atrial action potential to propagate into the ventricles 5. A System of Specialized Cardiac Muscle Cells Initiates and Organizes Each Heartbeat Slow conduction through the AV junction creates the delay between atrial and ventricular contractions. When past the slowly conducting cells of the AV junction, the cardiac action potential enters a branching network of specialized cardiac cells that have the property of extremely rapid propagation of action potentials. The transition zone from slowly conducting to rapidly conducting cells is located within the AV bundle, which has slowly conducting cells in its first portion(connected to the AV node) and rapidly conducting cells beyond that. The rapidly conducting portion of the AV bundle splits to form the left and right bundle branches. 5. A System of Specialized Cardiac Muscle Cells Initiates and Organizes Each Heartbeat At the ventricular apex, the bundle branches break up into a dispersed network of Purkinje fibers, which carry the action potential rapidly along the inner walls of both ventricles. The Purkinje fibers propagate action potentials into the normal ventricular muscle fibers within the inner walls (subendocardial layers) of both ventricles. From there, the action potentials propagate quite rapidly outward, from cell to cell, through the ventricular walls. As the action potential reaches each ventricular muscle fiber, that fiber contracts. 5. A System of Specialized Cardiac Muscle Cells Initiates and Organizes Each Heartbeat The extremely rapid conduction of the cardiac action potential, from cell to cell, through the latter portion of the AV bundle, the bundle branches, and the Purkinje system results in a nearly synchronous contraction of all the fibers in both ventricles. The SA and AV nodes, AV bundle, bundle branches, and Purkinje fibers are collectively called the specialized conduction system of the heart. This system is composed of specialized cardiac muscle cells, not nerves. the specialized conduction system cause each heartbeat to follow a specific, patterned sequence. In a normal beat, both atria contract, almost simultaneously. there is a brief pause (caused by slow propagation of the action potential through the AV node). 5. A System of Specialized Cardiac Muscle Cells Initiates and Organizes Each Heartbeat The two ventricles then contract, almost simultaneously. Finally, the entire heart relaxes and refills. in the “time lapse”, atrial excitation begins at time t = 0, when one SA node cell has reached threshold and an action potential is just beginning to propagate out of the SA node and into regular atrial tissue. Within 0.1 second, the action potential has propagated completely across the right and left atria, and a coordinated contraction of both atria is just beginning. As the action potential propagates across the atria, it also depolarizes the first cells in the AV node, beginning at time t = 0.04 second. While the atria are in a depolarized (excited) state, the action potential is propagating slowly from cell to cell through the AV node and first part of the AV bundle. 5. A System of Specialized Cardiac Muscle Cells Initiates and Organizes Each Heartbeat After traversing this slowly conducting region, the action potential propagates rapidly through the remainder of the bundle of His and its branches. The action potential arrives at the ventricular apex at time t = 0.17 second. it takes about 0.13 second [(0.17 − 0.04) second] for the action potential to travel through the AV node and bundles; that is, 0.13 second represents a typical delay between atrial depolarization and ventricular depolarization. From the ventricular apex, the Purkinje fibers propagate the action potential rapidly throughout both ventricles. Ventricular excitation (depolarization) is complete by time t = 0.22 second, and both ventricles contract. By this time the atria have repolarized to a resting state and are relaxing. After ventricular excitation and contraction, the ventricles relax, and the whole heart remains in a resting state until the next beat is originated by an SA node pacemaker cell. Specialized conduction system of the heart is responsible for the initiation and organization of cardiac contractions. The system is composed of specialized cardiac muscle fibers, not nerves. AV, Atrioventricular; SA, sinoatrial. Heart is pictured at four instants during initiation of a normal contraction. Shading indicates areas of heart where an action potential is underway. Top left (time = 0 sec), Pacemaker cell in the sinoatrial (SA) node has just reached threshold, and an action potential has begun to propagate outward across the atria. Top right (time = 0.1 sec), Action potential has reached all parts of both atria (action potentialunderway in all atrial cells). Middle left (time = 0.17 sec), Action potential has passed through the atrioventricular (AV) node and down the bundle branches and has just reached the ventricular apex. Middle right (time = 0.22 sec), Action potential has just finished propagating outward through the walls of both ventricles (action potential is underway in all ventricular cells, but all atrial cells have finished their action potential). Bottom, Graph shows the timing of action potentials in a left atrial cell (at location labeled A, top left) and in a left ventricular cell (labeled V, top left).Their locations make these among the last atrial 6. Cardiac Action Potentials Are Extremely Long Two major differences between action potentials in skeletal muscle and cardiac muscle : a. action potentials propagate from cell to cell in cardiac muscle, whereas skeletal muscle cells are electrically isolated from one another. b. the heart has pacemaker cells, which form spontaneous action potentials, whereas a skeletal muscle cell only depolarizes and forms action potentials when “commanded” to do so by its motor neuron. c. duration- the entire action potential in a skeletal muscle lasts only 1 to 2 msec.; a cardiac action potential lasts about 100 times longer (100-250 msec). 6. Cardiac Action Potentials Are Extremely Long Prolongation of the cardiac action potential is brought about by prolonged changes in the permeability of the cardiac muscle membrane to sodium, potassium, and calcium ions (Na+, K+, and Ca2+). Cardiac muscle cell membranes have Na+ and K+ channels similar to those found in skeletal muscle, but the timing of their opening and closing is different in cardiac muscle. cardiac cell membranes also have special Ca2+ channels that are not present in skeletal muscle. The movement of extracellular Ca2+ through cardiac Ca2+ channels has an especially important role in prolonging the cardiac action potential. 6. Cardiac Action Potentials Are Extremely Long The presence of Ca2+ channels and the important role of extracellular Ca2+ in the action potential is the fourth major difference between cardiac and skeletal muscle. the roles of K+ and Na+ channels in skeletal muscle and ways in which cardiac K+ and Na+ channels are similar to those in skeletal muscle. many of the K+ channels in a neuron or skeletal muscle cell membrane are open when the cell is at rest, and most of the Na+ channels are closed. thus, the resting cell is much more permeable to K+ than to Na+ also, there is a greater tendency for positive K+ to exit from the cell than for positive Na+ to enter. 6. Cardiac Action Potentials Are Extremely Long The imbalance is the main factor responsible for a resting membrane potential (polarization) in which the inside of the cell membrane is negative in comparison with the outside. The resting membrane potential in skeletal muscle cells is typically between –70 and –80 mV An action potential is created when something depolarizes the cell (makes it less negative inside). Specifically, depolarization to the threshold voltage for opening the voltage-gated Na+ channels allows an influx of extracellular Na+ into the cell. This rapid entry of positive ions causes the cell membrane to become positively charged on its inside surface. 6. Cardiac Action Potentials Are Extremely Long This positive membrane potential persists for only a moment, however, because the Na+ channels become inactivated very quickly. Na+ entry ceases, and the cell rapidly repolarizes toward its resting membrane potential. Repolarization is also promoted by the opening of additional K+ channels. this opening of extra K+ channels may cause neurons and skeletal muscle cells to become hyperpolarized (even more negative than normal resting membrane potential) for a few milliseconds at the end of each action potential In a resting skeletal muscle cell, calcium ions are sequestered within the sarcoplasmic reticulum. The occurrence of an action potential in the skeletal muscle cell causes Ca2+ to be released from the sarcoplasmic reticulum into the free intracellular fluid, which is called the cytosol. 6. Cardiac Action Potentials Are Extremely Long The increase in cytosolic Ca2+ concentration initiates muscle contraction The contraction initiated by a single action potential is very brief in skeletal muscle, because the cytosolic Ca2+ is rapidly pumped back into the sarcoplasmic reticulum by active transport, and the muscle relaxes. the Ca2+ responsible for initiating skeletal muscle contraction comes entirely from the intracellular storage site, the sarcoplasmic reticulum. No extracellular Ca2+enters the cell during the action potential, because skeletal muscle cells do not have membrane Ca2+ channels. In cardiac muscle, in contrast, membrane Ca2+ channels Action potentials in cardiac muscle cells (top) last 100 times longer than action potentials in nerve or skeletal muscle cells (middle). Bottom, The nerve or skeletal muscle action potential is shown on a greatly expanded time scale to illustrate that an action potential in a nerve or skeletal muscle cell has a different shape than a cardiac action potential, as well as a much shorter duration. The prolonged phase of depolarization in cardiac muscle cells is called the plateau of the action potential. The dark bars under each action 7. Membrane Calcium Channels Play a Special Role in Cardiac Muscle cardiac muscle cell action potential and the sequence of changes in K+, Na+, and Ca2+ permeability that are responsible for the action potential: left side of graph: time line begins--- the cardiac cell is at a normal, negative resting membrane potential of about –80 mV. The cardiac membrane potential is negative at rest for the same reason that skeletal muscle cells have negative resting membrane potentials: many K+channels are open at rest, and most of the Na+ channels are closed. As a result, membrane permeability to K+ is much higher than membrane permeability to Na+ In resting cardiac cells, the membrane Ca2+ channels are 7. Membrane Calcium Channels Play a Special Role in Cardiac Muscle when the cell is depolarized to the threshold voltage for opening the voltage-gated Na+ channels-- rapid influx of extracellular Na+ into the cell causes the cell membrane to become positively charged on its inside surface (Phase 0)--- the Na channels inactivate very quickly, which causes the Na+ permeability to decrease quickly; the membrane begins to repolarize (Phase 1). in cardiac muscle, repolarization is interrupted, and there is a prolonged plateau of depolarization, which lasts about 200 msec (Phase 2). T The plateau of the cardiac action potential is because of two conditions that do not occur in nerves or skeletal muscle fibers: (1) some K+ channels close, so K+ permeability decreases; and (2) many of the Ca2+ channels open, so Ca2+ permeability increases. 7. Membrane Calcium Channels Play a Special Role in Cardiac Muscle since the Ca2+ concentration is higher in the extracellular fluid than in the intracellular fluid, Ca2+ flows through the open Ca2+ channels and into the cytosol. The combination of reducing the exit of K+ from the cell and allowing the entrance of Ca2+ into the cell keeps the cell membrane in a depolarized state. After about 200 msec, the K+channels reopen, and the Ca2+ channels close; K+ permeability increases, and Ca2+ permeability decreases The combination of increasing the exit of K+ from the cell and shutting off the entrance of Ca2+ into the cell causes the cell to repolarize (Phase 3) and eventually to return to its stable, negative resting membrane potential (Phase 4). The specialized Ca2+ channels in cardiac muscle cell membranes are called slow Ca2+ channels (or L-type Ca2+ channels)- take much longer to open than the Na+ channels, and they stay open much longer. 7. Membrane Calcium Channels Play a Special Role in Cardiac Muscle Na+permeability increases and then decreases (Na+ channels open and then inactivate) within a few milliseconds. Ca2+ permeability, is slow to increase (Ca2+ channels are slow to open) and Ca2+ permeability remains elevated for about 200 msec (the time Ca2+ channels stay open). the Na+ channels in cardiac muscle are sometimes called fast Na+ channels- since fast response The Ca2+ that enters a cardiac cell during an action potential triggers the release of additional Ca2+ from the sarcoplasmic reticulum. This process is called calcium-triggered calcium release(or calcium-induced calcium release). In less than 0.1 second, the contraction of free Ca2+ in the cytosol increases about 100-fold. As in skeletal muscle, this increase in cytosolic Ca2+ initiates concentration. 7. Membrane Calcium Channels Play a Special Role in Cardiac Muscle When the Ca2+ channels close, at the conclusion of the action potential, most of the free, cytosolic Ca2+ is pumped back into the sarcoplasmic reticulum or pumped back across the cell membrane into the extracellular fluid. these processes involve active transport, because the Ca2+ is being pumped against its electrochemical gradient. Once the cytosolic Ca2+ concentration is returned to its low, resting level, the cardiac muscle relaxes. Na+ channels become inactivated at the peak of the cardiac action potential. Na+ cannot pass through an inactivated channel; therefore, as long as the Na+ channels remain inactivated, another action potential cannot occur. Membrane potential of a cardiac muscle cell (top) is deter_x0002_mined by the relative permeabilities of the cell membrane to K+ (second from top), Na+ (second from bottom), and Ca2+ (bottom). At rest (left sideof graphs), the cell is much more permeable to K+ than to Na+ or Ca2+.(That is, the number of open K+ channels greatly exceeds the number ofopen Na+ or Ca2+ channels.) A cardiac action potential (middle of graphs) is produced by a characteristic sequence of permeability changes to K+,Na+, and Ca2+ (i.e., changes in the number of open K+,Na+, and Ca2+channels). The action potential ends when the permeabilities return to theirresting state (right side of graphs). Phases 0 to 4 are 8. The Long Duration of the Cardiac Action Potential Guarantees a Period of Relaxation (and Refilling) Between Heartbeats The inactivated state ends, and Na+ channels become susceptible to reopening only when the cell membrane potential returns to (or nearly to) its resting level. Thus, Na+ inactivation guarantees that the upstroke of a second action potential cannot occur until the first action potential is completed (or very nearly) While the Na+ channels are inactivated, the cell is refractory(resistant) with regard to the formation of an action potential. The time after the beginning of one action potential during which another action potential cannot be initiated is called the absolute refractory period. Because Na+ inactivation lasts until the membrane potential returns to (or nearly to) its resting level, the refractory period lasts about as long as an action potential. The first of three cardiac action potentials (solid line, top)causes a cardiac contraction (solid line, bottom). Note that the actionpotential and contraction have similar durations. The heavy horizontal bar under the first action potential shows the duration of the absolute refractory period. The dashed line and dotted line in the top graph show the earliest possible occurrence of a second and a third action potential, each occurring right after the absolute refractory period for the preceding action potential. The dashed line and dotted line in the bottom graph depict the corresponding cardiac contractions. Because of the long refractory period, each contraction is almost over before the earliest possible next contraction can begin. This guarantees a period of cardiac relaxation between 8. The Long Duration of the Cardiac Action Potential Guarantees a Period of Relaxation (and Refilling) Between Heartbeats the refractory period in a cardiac muscle cell lasts 100 to 250 msec, whereas the refractory period in a nerve or skeletal muscle cell lasts only about 1 or 2 msec The long refractory period in cardiac muscle guarantees a period of relaxation (and cardiac refilling) between cardiac contractions. the quickest possible succession of three action potentials in a cardiac muscle cell: the second action potential begins immediately after the conclusion of the refractory period for the first action potential; the third action potential begins immediately after the conclusion of the refractory period for the second. 8. The Long Duration of the Cardiac Action Potential Guarantees a Period of Relaxation (and Refilling) Between Heartbeats Note that contractile strength reaches a peak late in the plateau phase of each action potential, and that the contractile strength decreases (the muscle begins to relax) during the repolarization phase of each action potential. As a result, the cardiac muscle cell becomes partially relaxed before the earliest possible subsequent contraction can begin; that is, each cardiac action potential produces a contraction that is distinctly separated from the preceding contraction. Because of its long refractory period, cardiac muscle cannot sustain a continuous contraction. Thus the heart has a guaranteed period of relaxation (and refilling) between heartbeats. 8. The Long Duration of the Cardiac Action Potential Guarantees a Period of Relaxation (and Refilling) Between Heartbeats The pattern of changes in muscle tension corresponds closely to the changes in the cytosolic Ca2+ concentration. the increase in cytosolic Ca2+ concentration initiates muscle contraction, and the subsequent removal of Ca2+ from the cytosol permits the muscle to relax. Cytosolic Ca2+ concentration increases during the plateau of the action potential (because of Ca2+-triggered Ca2+ release) and decreases back to its resting level during the repolarization phase of the action potential (as active transport pumps move Ca2+ back into the sarcoplasmic reticulum or out into the extracellular fluid). In skeletal muscle cells, an action potential lasts only 1 to 2 msec. The membrane is repolarized (and the refractory period is over) even before the release of Ca2+ from the sarcoplasmic reticulum is finished, and many milliseconds before the released Ca2+is pumped back into the sarcoplasmic reticulum. 8. The Long Duration of the Cardiac Action Potential Guarantees a Period of Relaxation (and Refilling) Between Heartbeats the cytosolic Ca2+ concentration reaches its peak level after the action potential is over, and the contractile tension resulting from the action potential also reaches its peak after the action potential is over. since a contractile twitch lasts much longer than the refractory period in skeletal muscle, several action potentials can occur during the time of a single contractile twitch. temporal summation: Multiple action potentials in quick succession cause cytosolic Ca2+ concentration to build to a high level and stay there. The resulting contractile tension is stronger than the tension that results from a single action potential, and it is sustained for a longer time. In effect, the muscle twitches caused by successive action potentials “fuse” together. 8. The Long Duration of the Cardiac Action Potential Guarantees a Period of Relaxation (and Refilling) Between Heartbeats Fusion and temporal summation are the mechanisms that permit graded and prolonged tension development in skeletal muscle. In contrast, the long refractory period in cardiac muscle cells prevents the fusion and summation of cardiac contractions. Each contraction of the heart (each heartbeat) is followed immediately by a relaxation. The previous description of cardiac ion channels, action potentials, and contractions is based on properties of normal ventricular cells. Atrial cells are basically similar, except that their action potentials are shorter than action potentials in ventricular cells. 8. The Long Duration of the Cardiac Action Potential Guarantees a Period of Relaxation (and Refilling) Between Heartbeats Like ventricular cells, atrial cells have fast Na+ channels that open briefly at the beginning of an action potential and then become inactivated. Likewise, atrial slow Ca2+ channels open during the action potential, and K+ channels close. The differences between atrial and ventricular cells are that atrial slow Ca2+ channels typically stay open a shorter time than those in ventricular cells, and atrial K+ channels stay closed for a shorter time. 9. Atrial Cells Have Shorter Action Potentials Than Ventricular Cells As a result, the plateau of an atrial cell’s action potential is shorter and not as “flat” as the plateau of a ventricular cell’s action potential As a consequence of having a shorter action potential, atrial cells have a shorter refractory period than ventricular cells. Therefore the atrial cells are capable of forming more action potentials per minute than ventricular cells; that is, the atria can “beat” faster than the ventricles. 10. Specialized Ion Channels Cause Cardiac Pacemaker Cells to Depolarize to Threshold and Form Action Potentials the cardiac pacemaker cells of the SA node spontaneously depolarize to threshold and then form action potentials. The spontaneous depolarization is called a pacemaker potential, and it is the key distinguishing feature of a pacemaker cell The action potentials of cardiac pacemaker cells typically have a rounded appearance; they lack the very rapid (phase 0) depolarization seen in ventricular and atrial cells. The spontaneous depolarizations and rounded action potentials of pacemaker cells are consequences of the 10. Specialized Ion Channels Cause Cardiac Pacemaker Cells to Depolarize to Threshold and Form Action Potentials Pacemaker cells lack the usual voltage-gated fast Na+ channels. but cells have pacemaker Na+ channels, which close during an action potential and then begin to open again, spontaneously, once an action potential has finished. The spontaneous opening of the pacemaker Na+ channels causes a progressive increase in the cell’s Na+ permeability The increase in Na+ permeability allows Na+ to enter the cell from the extracellular fluid, which depolarizes the cell toward threshold. Pacemaker cells also have an unusual set of K+channels, which participate in their spontaneous depolarization. 10. Specialized Ion Channels Cause Cardiac Pacemaker Cells to Depolarize to Threshold and Form Action Potentials At the end of one action potential, K+ permeability in pacemaker cells is quite high, because most K+ channels are open. Then some K+ channels begin to close As K+ permeability decreases, less K+ leaves the cells, which makes the cells progressively less negatively charged inside. Ca2+ channels also make a small contribution to the pacemaker potential. Late in the pacemaker potential, just before a pacemaker cell reaches threshold, slow Ca2+channels begin to open, and Ca2+ permeability begins to increase The resulting entry of Ca2+ into the cell speeds its final approach to threshold. Thus the pacemaker potential is caused by the opening of pacemaker Na+ channels, the closing of K+ channels, and (late in the process) the opening of Ca2+channels. 10. Specialized Ion Channels Cause Cardiac Pacemaker Cells to Depolarize to Threshold and Form Action Potentials spontaneous changes in Na+, K+, and Ca2+ channels in pacemaker cells are in contrast to the stable status of the ion channels in normal, resting atrial or ventricular cells. When threshold is reached in a pacemaker cell, an action potential occurs. The upstroke of the action potential is quite slow compared with the rapid (phase 0) depolarization in a normal atrial or ventricular cell, because there are no fast Na+ channels in pacemaker cells and therefore no sudden influx of Na+ The ion primarily responsible for the action potential in a pacemaker cell is Ca2+ When threshold is reached, many of the cell’s slow Ca2+channels open. 10. Specialized Ion Channels Cause Cardiac Pacemaker Cells to Depolarize to Threshold and Form Action Potentials The permeability to Ca2+ increases, and extracellular Ca2+ flows into the cell. The action potentials in pacemaker cells are often called slow action potentials, because they lack a rapid, phase 0 depolarization and because they are caused primarily by the opening of slow Ca2+ channels. In contrast, normal atrial or ventricular action potentials are called fast action potentials. all cardiac action potentials (whether “slow” or “fast”) have a very long duration compared with action potentials in nerve or skeletal muscle cells. A cardiac pacemaker cell depolarizes spontaneously to threshold and initiates its own action potential (top). The spontaneous depolarization (called the pacemaker potential) is the result of a spontane_x0002_ous, progressive decrease in K+ permeability (second from top) and an increase in Na+ permeability (second from bottom). An increase in Ca2+ permeability makes a late contribution to the depolarization toward thresh_x0002_old (bottom). When threshold level is reached, an action potential is pro_x0002_duced. The action potential is driven primarily by a large, prolonged increase in Ca2+ permeability. The absence of fast Na+ channels in pacemaker cells causes the upstroke of the pacemaker action potential 11. Sympathetic and Parasympathetic Nerves Act on Cardiac Pacemaker Cells to Increase or Decrease the Heart Rate how the neurotransmitters norepinephrine and acetylcholine affect the pacemaker cells of the heart: Norepinephrine exerts its effect by activating β-adrenergic receptors on the cell membranes of pacemaker cells. Activation of such receptors speeds up the ion channel changes that are responsible for the spontaneous depolarization of pacemaker cells. Because the pacemaker cells reach threshold more quickly in the presence of norepinephrine, there is a shorter interval between heartbeats. Therefore, heart rate is elevated above its intrinsic or spontaneous level. 11. Sympathetic and Parasympathetic Nerves Act on Cardiac Pacemaker Cells to Increase or Decrease the Heart Rate Acetylcholine has the opposite effect. Acetylcholine activates muscarinic cholinergic receptors on the cell membranes of pacemaker cells, which slows the ion channel changes that are responsible for the pacemaker cell’s spontaneous depolarization. Because the pacemaker cells take longer to reach threshold in the presence of acetylcholine, there is a longer interval between heartbeats. Therefore, heart rate is decreased below its intrinsic or spontaneous level. Sympathetic neurons release norepinephrine at the SA node cells, and thus sympathetic nerve activity increases the heart rate. 11. Sympathetic and Parasympathetic Nerves Act on Cardiac Pacemaker Cells to Increase or Decrease the Heart Rate Epinephrine or norepinephrine, released from the adrenal glands and circulating in the bloodstream, has the same effect. Parasympathetic neurons release acetylcholine at the SA node cells, and thus parasympathetic activity decreases the heart rate. In the absence of norepinephrine and acetylcholine, the heart beats at its intrinsic rate. For a large dog, this rate is typically about 140 beats per minute (beats/min). Heart rates below the intrinsic rate are achieved by activation of parasympathetic neurons and release of 11. Sympathetic and Parasympathetic Nerves Act on Cardiac Pacemaker Cells to Increase or Decrease the Heart Rate parasympathetic activity is high during awake rest (heart rate of 90 beats/min) and very high during sleep (heart rate of 55 beats/min). Heart rates above the intrinsic rate occur during exercise or emotional arousal and are achieved by activation of the sympathetic nerves to the heart and release of norepinephrine (or bycirculating epinephrine or norepinephrine). The highest possible level of sympathetic activity, and therefore the highest possible heart rate, occurs during maximal exercise or a defense alarm reaction (“fear, fight, or flight” response). Through variation in the levels of sympathetic and parasympathetic tone, the dog’s heart rate is adjusted, over a wide range, as appropriate for each behavioral situation. 11. Sympathetic and Parasympathetic Nerves Act on Cardiac Pacemaker Cells to Increase or Decrease the Heart Rate When both systems are partially active, the resulting heart rate represents the outcome of a “tug-of-war” between sympathetic action to increase the heart rate and parasympathetic action to decrease the heart rate. Typically, the sympathetic and parasympathetic systems are both partially active during awake states, ranging from quiet rest (heart rate about 90 beats/min) to moderate exercise (heart rate about 175 beats/min). Parasympathetic activity predominates in the lower part of this range, and sympathetic activity predominates in the higher part. When sympathetic activity and parasympathetic activity are equal, their effects cancel, and the heart rate is at its intrinsic (spontaneous) level. Simultaneous activation of sympathetic and parasympathetic neurons appears to give the nervous system tight control over the heart rate under a wide variety of behavioral conditions. In the absence of neurohumoral influences, a pacemaker cell of the SA node spontaneously depolarizes to threshold and initiates a series of action potentials, three of which are shown by the black line. The interval between action potentials under these conditions determines the intrinsic, or spontaneous, heart rate (in this case, 0.43 sec between action potentials corresponds to a heart rate of 140 beats/min). Acetylcholine decreases the rate of depolarization and therefore lengthens the interval between action potentials (i.e., decreases heart rate). Norepinephrine increases the rate of The upper scale shows that the heart rate of a normal, large dog ranges from 50 to 250 beats/min, depending on behavioral state. The graph illustrates that this wide range of heart rates is brought about by the interactions between sympathetic nerve activity, which speeds the heart above its intrinsic rate, and parasympathetic nerve activity, which slows the heart below its intrinsic rate. Sympathetic and parasympathetic nerves are simultaneously active over a considerable portion of the heart rate range (overlapping control). Note that the heart beats at its intrinsic rate 12. Cells of the Atrioventricular Node Act as Auxiliary Pacemakers and Protect the Ventricles from Beating Too Fast As with SA node cells, the cells of the AV node normally exhibit pacemaker activity and slow action potentials. the AV node cells spontaneously depolarize toward threshold, but much more slowly than SA node cells. under normal circumstances, the SA node cells reach threshold first and initiate an action potential, which then propagates from cell to cell across the atria and into the AV node. Within the AV node, this action potential encounters cells that are slowly, spontaneously depolarizi

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