•A liquid, blood, to transport
◦nutrients
◦wastes
◦oxygen and carbon dioxide
◦hormones
•Two pumps (in a single heart)
◦one to pump deoxygenated blood to the lungs;
◦the other to pump oxygenated blood to all the other organs and tissues of the body.
•A system of blood vessels to distribute blood throughout the body
•Specialized organs for exchange of materials between the blood and the external environment; for example
◦organs like the lungs and intestine that add materials to the blood and
◦organs like the lungs and kidneys that remove materials from the blood and deposit them back in
the external environment.
The heart and pulmonary system
The heart is located roughly in the center of the chest cavity. It is covered by a protective membrane, the pericardium.
•Deoxygenated blood from the body enters the right atrium.
•It flows through the tricuspid valve into the right ventricle. The term tricuspid refers to the three flaps of tissue that make up the valve.
•Contraction of the ventricle then closes the tricuspid valve and forces open the pulmonary valve.
•Blood flows into the pulmonary artery.
•This branches immediately, carrying blood to the right and left lungs.
•Here the blood gives up carbon dioxide and takes on a fresh supply of oxygen.
•The capillary beds of the lungs are drained by venules that are the tributaries of the pulmonary veins.
•Four pulmonary veins, two draining each lung, carry oxygenated blood to the left atrium of the heart
Below: the human heart, with a schematic view of the pathway of blood through the lungs and internal organs. Oxygenated blood is shown in red; deoxygenated blood in blue. Note that the blood draining the stomach, spleen, and intestines passes through the liver before it is returned to the heart. Here surplus or harmful materials picked up from those organs can be removed before the blood returns to the general circulation. [Graphic of this hepatic portal system]
The coronary system
From the left atrium,
•Blood flows through the mitral valve (also known as the bicuspid valve) into the left ventricle.
•Contraction of the ventricle closes the mitral valve and opens the aortic valve at the entrance to the aorta.
•The first branches from the aorta occur just beyond the aortic valve still within the heart.
•Two openings lead to the right and left coronary arteries, which supply blood to the heart itself.
Although the coronary arteries arise within the heart, they pass directly out to the surface of the heart and extend down across it. They supply blood to the network of capillaries that penetrate every portion of the heart.
•The capillaries drain into two coronary veins that empty into the right atrium.
Arteriosclerosis
The coronary arteries arise at the point of maximum blood pressure in the circulatory system. Over the course of time, the arterial walls are apt to lose elasticity, which limits the amount of blood that can surge through them and hence limits the supply of oxygen to the heart. This condition is known as arteriosclerosis.
Atherosclerosis
Fatty deposits, called plaque, may accumulate on the interior surface of the coronary arteries. This is particularly common in people who have high levels of cholesterol in their blood. Plaque deposits reduce the bore of the coronary arteries and thus the amount of blood they can carry.
Atherosclerosis (usually along with arteriosclerosis) may
•so limit the blood supply to the heart that during times of stress the heart muscle is so deprived of oxygen that the pain of angina is created.
•trigger the formation of a clot causing a coronary thrombosis. This stops the flow of blood through the vessel and the capillary network it supplies causing a heart attack. The portion of the heart muscle deprived of oxygen dies quickly of oxygen starvation. If the area is not too large, the undamaged part of the heart can, in time, compensate for the damage.
Coronary bypass surgery uses segments of leg veins to bypass the clogged portions of the coronary arteries.
The remainder of the system is known as the systemic circulation. The graphic shows the major arteries (in bright red) and veins (dark red) of the system.
Blood from the aorta passes into a branching system of arteries that lead to all parts of the body. It then flows into a system of capillaries where its exchange functions take place.
Blood from the capillaries flows into venules which are drained by veins.
•Veins draining the upper portion of the body lead to the superior vena cava.
•Veins draining the lower part of the body lead to the inferior vena cava.
•Both empty into the right atrium.
During rest, the heart beats about 70 times a minute in the adult male, while pumping about 5 liters of blood.
The stimulus that maintains this rhythm is self-contained. Embedded in the wall of the right atrium is a mass of specialized heart tissue called the sino-atrial (S-A) node. The S-A node is also called the pacemaker because it establishes the basic frequency at which the heart beats.
The interior of the fibers of heart muscle, like all cells, is negatively charged with respect to the exterior. In the cells of the pacemaker, this charge breaks down spontaneously about 70 times each minute. This, in turn, initiates a similar discharge of the nearby muscle fibers of the atrium. A tiny wave of current sweeps over the atria, causing them to contract.
When this current reaches the region of insulating connective tissue between the atria and the ventricles, it is picked up by the A-V node (atrio-ventricular node). This leads to a system of branching fibers that carries the current to all parts of the ventricles.
The contraction of the heart in response to this electrical activity creates systole.
A period of recovery follows called diastole.
•The heart muscle and S-A node become recharged.
•The heart muscle relaxes.
•The atria refill.
The Electrocardiogram
The electrical activity of the heart can be detected by electrodes placed at the surface of the body. Analysis of an electrocardiogram (ECG or EKG) aids in determining, for example, the extent of damage following a heart attack. This is because death of a portion of the heart muscle blocks electrical transmission through that area and alters the appearance of the ECG.
Ventricular Fibrillation
The ventricles can maintain a beat even without a functioning A-V node, although the beat is slower. There is, however, a danger that impulses arising in the ventricles may become disorganized and random. If this happens, they begin to twitch spasmodically, a condition called ventricular fibrillation. Blood flow ceases and unless the heart rhythm is restarted, death follows swiftly. In fact, ventricular fibrillation is the immediate cause of as much as 25% of all deaths.
Hospital emergency rooms, ambulances, and (recently) commercial air craft are routinely equipped with defibrillators which, by giving the heart a jolt of direct current, may restore its natural rhythm and save the victim's life.
Artificial Pacemakers
These are devices that generate rhythmic impulses that are transmitted to the heart by fine wires. Thanks to miniaturization and long-lived batteries, pacemakers can be implanted just under the skin and reached through a small incision when maintenance is needed. Auxiliary Control of the Heart
Although the A-V node sets the basic rhythm of the heart, the rate and strength of its beating can be modified by two auxiliary control centers located in the medulla oblongata of the brain.
•One sends nerve impulses down accelerans nerves.
•The other sends nerve impulses down a pair of vagus nerves
The Accelerans Nerve
The accelerans nerve is part of the sympathetic branch of the autonomic nervous system, and — like all post-ganglionic sympathetic neurons — releases noradrenaline at its endings on the heart.
It increases the rate and strength of the heartbeat and thus increase the flow of blood. Its activation usually arises from some stress such as fear or violent exertion. The heartbeat may increase to 180 beats per minute. The strength of contraction increases as well so the amount of blood pumped may increase to as much as 25-30 liters/minute.
The 24 Feb 2000 issue of the New England Journal of Medicine reports on a family some of whose members have inherited a mutant gene for the transporter that is responsible for reuptake of noradrenaline back into the neuron that released it. Those with the mutation are prone to bouts of rapid heartbeat and fainting when they suddenly stand up.
Vigorous exercise accelerates heartbeat in two ways;
•As cellular respiration increases, so does the carbon dioxide level in the blood. This stimulates receptors in the carotid arteries and aorta, and these transmit impulses to the medulla for relay — by the accelerans nerve — to the heart.
•As muscular activity increases, the muscle pump drives more blood back to the right atrium. The atrium becomes distended with blood, thus stimulating stretch receptors in its wall. These, too, send impulses to the medulla for relay to the heart.
(Distention of the wall of the right atrium also triggers the release of atrial natriuretic peptide (ANP) which initiates a set of responses leading to a lowering of blood pressure.
The Vagus Nerves
The vagus nerves are part of the parasympathetic branch of the autonomic nervous system. They, too, run from the medulla oblongata to the heart. Their activity slows the heartbeat.
Pressure receptors in the aorta and carotid arteries send impulses to the medulla which relays these — by way of the vagus nerves — to the heart. Heartbeat and blood pressure diminish.
How Cardiovascular System Works
All the functions of the circulatory system occur in the capillary beds. The rest of the system consists of two pumps (in the heart) and associated plumbing:
•arteries
•their terminal branches, the arterioles
•veins
•and their tributaries, the venules.
Blood Pressure
Blood moves through the arteries, arterioles, and capillaries because of the force created by the contraction of the ventricles.
Blood pressure in the arteries.
The surge of blood that occurs at each contraction is transmitted through the elastic walls of the entire arterial system where it can be detected as the pulse. Even during the brief interval when the heart is relaxed — called diastole — there is still pressure in the arteries. When the heart contracts — called systole — the pressure increases.
Blood pressure is expressed as two numbers, e.g., 120/80.
The first is the pressure during systole. The unit of measure is the torr, in this example, the pressure equivalent to that produced by a column of mercury 120 mm high. The second number is the pressure at diastole.
Although blood pressure can vary greatly in an individual, continual high pressure — especially diastolic pressure — may be the symptom or cause of a variety of ailments. The medical term for high blood pressure is hypertension.
Blood pressure in the capillaries
The pressure of arterial blood is largely dissipated when the blood enters the capillaries. Capillaries are tiny vessels with a diameter just about that of a red blood cell (7.5 µm). Although the diameter of a single capillary is quite small, the number of capillaries supplied by a single arteriole is so great that the total cross-sectional area available for the flow of blood is increased. Therefore, the pressure of the blood as it enters the capillaries decreases.
Blood pressure in the veins
When blood leaves the capillaries and enters the venules and veins, little pressure remains to force it along. Blood in the veins below the heart is helped back up to the heart by the muscle pump. This is simply the squeezing effect of contracting muscles on the veins running through them. One-way flow to the heart is achieved by valves within the veins.
With rare exceptions, our blood does not come into direct contact with the cells it nourishes. As blood enters the capillaries surrounding a tissue space, a large fraction of it is filtered into the tissue space. It is this interstitial or extracellular fluid (ECF) that brings to cells all of their requirements and takes away their products. The number and distribution of capillaries is such that probably no cell is ever farther away than 50 µm from a capillary.
When blood enters the arteriole end of a capillary, it is still under pressure (about 35 torr) produced by the contraction of the ventricle. As a result of this pressure, a substantial amount of water and some plasma proteins filter through the walls of the capillaries into the tissue space.
Thus fluid, called interstitial fluid, is simply blood plasma minus most of the proteins. (It has the same composition and is formed in the same way as the nephric filtrate in kidneys.)
Interstitial fluid bathes the cells in the tissue space and substances in it can enter the cells by diffusion or active transport. Substances, like carbon dioxide, can diffuse out of cells and into the interstitial fluid.
Near the venous end of a capillary, the blood pressure is greatly reduced (to about 15 torr). Here another force comes into play. Although the composition of interstitial fluid is similar to that of blood plasma, it contains a smaller concentration of proteins than plasma and thus a somewhat greater concentration of water. This difference sets up an osmotic pressure. Although the osmotic pressure is small (~ 25 torr), it is greater than the blood pressure at the venous end of the capillary. Consequently, the fluid reenters the capillary here.
Control of the Capillary Beds
An adult human has been estimated to have some 60,000 miles of capillaries with a total surface area of some 800–1000 m2 (an area greater than three tennis courts). The total volume of this system is roughly 5 liters, the same as the total volume of blood. However, if the heart and major vessels are to be kept filled, all the capillaries cannot be filled at once. So a continual redirection of blood from organ to organ takes place in response to the changing needs of the body. During vigorous exercise, for example, capillary beds in the skeletal muscles open at the expense of those in the viscera. The reverse occurs after a heavy meal.
The walls of arterioles are encased in smooth muscle. Constriction of arterioles decreases blood flow into the capillary beds they supply while dilation has the opposite effect. In time of danger or other stress, for example, the arterioles supplying the skeletal muscles will be dilated while the bore of those supplying the digestive organs will decrease. These actions are carried out by
•the autonomic nervous system.
•local controls in the capillary beds
Local Control in the Capillary Beds
•Nitric oxide (NO) is a potent dilator of arteries and arterioles.
◦When the endothelial cells that line these vessels are stimulated, they synthesize nitric oxide. It quickly
diffuses into the muscular walls of the vessels causing them to relax.
◦In addition, as the hemoglobin in red blood cells releases its O2 in actively-respiring tissues, the
lowered pH causes it to also release NO which helps dilate the vessels to meet the increased need of
the tissue.
Nitroglycerine, which is often prescribed to reduce the pain of angina, does so by generating nitric oxide, which relaxes the walls of the arteries and arterioles. The prescription drug sildenafil citrate ("Viagra") does the same for vessels supplying blood to the penis. The effects of these two drugs are additive and using them together could precipitate a dangerous drop in blood pressure.
Role of NO in CVS
Blood Flow
NO relaxes the smooth muscle in the walls of the arterioles. At each systole, the endothelial cells that line the blood vessels release a puff of NO. This diffuses into the underlying smooth muscle cells causing them to relax and thus permit the surge of blood to pass through easily. Mice whose genes for the NO synthase found in endothelial cells (eNOS) has been "knocked out" suffer from hypertension.
Nitroglycerine, which is often prescribed to reduce the pain of angina, does so by generating nitric oxide, which relaxes the walls of the coronary arteries and arterioles.
Three of the pioneers in working out the biological roles of NO shared a Nobel Prize in 1998 for their discoveries. The award to one of them, Ferid Murad, honored his discovery that nitroglycerine works by releasing NO. This seems particularly appropriate because Alfred Nobel's fortune came from his invention of making dynamite from nitroglycerine!
NO also inhibits the aggregation of platelets and thus keeps inappropriate clotting from interfering with blood flow.
Kidney Function
Release of NO around the glomeruli of the kidneys increases blood flow through them thus increasing the rate of filtration and urine formation.
•Cells where infection or other damage is occurring release substances like histamine that dilate the arterioles and thus increase blood flow in the area.
•In most of the body, the flow of blood through a capillary is controlled by the arteriole supplying it. In the brain, however, another mechanism participates. The degree of contraction of pericytes, cells that surround the capillary, also adjusts the flow of blood through the capillary. The changes in brain activity seen by such imaging procedures as fMRI and PET scans are probably influenced by pericyte activity.
Shock
Under some circumstances, capillary beds may open without others closing in compensation. Although the volume of blood remains unchanged, blood pressure declines abruptly as blood pools in the capillary beds. If untreated shock is usually fatal.
Shock can also result from severe bleeding. The heart can only pump as much blood as it receives. If insufficient blood gets back to the heart, its output — and hence blood pressure — drops. The tissues fail to receive enough oxygen. This is especially critical for the brain and the heart itself. To cope with the problem, arterioles constrict and shut down the capillary beds — except those in the brain and heart. This reduces the volume of the system and helps maintain normal blood pressure.
Air-breathing vertebrates that spend long periods under water (e.g., seals, penguins, turtles, and alligators) employ a similar mechanism to ensure that the oxygen supply of the heart and brain is not seriously diminished. When the animal dives, the blood supply to the rest of the body is sharply reduced so that what oxygen remains will be available for those organs needing it most: the brain and heart.
The Kidney
One of the functions of the kidney is to monitor blood pressure and take corrective action if it should drop. The kidney does this by secreting the proteolytic enzyme renin.
•Renin acts on angiotensinogen, a plasma peptide, splitting off a fragment containing 10 amino acids called
•angiotensin I.
•angiotensin I is cleaved by a peptidase secreted by blood vessels called angiotensin converting enzyme (ACE) — producing
•angiotensin II, which contains 8 amino acids.
•angiotensin II
◦constricts the walls of arterioles closing down capillary beds;
◦stimulates the proximal tubules in the kidney to reabsorb sodium ions;
◦stimulates the adrenal cortex to release aldosterone. Aldosterone causes the kidneys to reclaim still
more sodium and thus water .
◦increases the strength of the heartbeat;
◦stimulates the pituitary to release the vasopressin.
All of these actions, which are mediated by its binding to G-protein-coupled receptors on the target cells, lead to an increase in blood pressure.
Among the drugs prescribed to treat people with high blood pressure (hypertension) are
•ACE inhibitors like quinapril , ramipril , lisinopril
•Angiotensin-receptor blockers — drugs like losartan and olmesartan that interfere with the binding of angiotensin II to its receptors (e.g., on the adrenal cortex).
•Ca2+ channel blockers like felodipine,Amlodipine, that inhibit the influx of the Ca2+ ions that cause the smooth muscle walls of the arterioles to contract.
The Heart
A rise in blood pressure stretches the atria of the heart. This triggers the release of atrial natriuretic peptide (ANP). ANP is a peptide of 28 amino acids. ANP lowers blood pressure by:
•relaxing arterioles
•inhibiting the secretion of renin and aldosterone
•inhibiting the reabsorption of sodium ions in the collecting ducts of the kidneys.
The effects on the kidney reduce the reabsorption of water by them thus increasing the flow of urine and the amount of sodium excreted in it (These actions give ANP its name: natrium = sodium; uresis = urinate). The net effect of these actions is to reduce blood pressure by reducing the volume of blood volume in the system.
