Blood consists of formed elements that are suspended and carried in a fluid called plasma. The formed elements, erythrocytes, leukocytes, and platelets function, respectively, in oxygen transport, immune defense, and blood clotting.  The total blood volume in the average-size adult is about 5 liters, constituting about 8% of the total body weight. Blood leaving the heart is referred to as arterial blood. Arterial blood, with the exception of that going to the lungs, is bright red because of a high concentration of oxyhemoglobin (the combination of oxygen and hemoglobin) in the red blood cells. Venous blood is blood returning to the heart. Except for the venous blood from the lungs, it contains less oxygen and

is therefore a darker red than the oxygen-rich arterial blood. Blood is composed of a cellular portion, called formed elements, and a fluid portion, called plasma. When a blood sample is centrifuged, the heavier formed elements are packed into the bottom of the tube, leaving plasma at the top. The formed elements constitute approximately 45% of the total blood volume, and the plasma accounts for the remaining 55%. Red blood cells compose most of the formed elements; the percentage of red blood cell volume to total blood volume in a centrifuged blood sample (a measurement called the hematocrit) is 36% to 46% in women and 41% to 53% in men.




Plasma is a straw-colored liquid consisting of water and dissolved solutes. The major solute of the plasma in terms of its concentration is Na+. In addition to Na+, plasma contains many other ions, as well as organic molecules such as metabolites, hormones, enzymes, antibodies, and other proteins.


Plasma Proteins

Plasma proteins constitute 7% to 9% of the plasma. The three types of proteins are albumins, globulins, and fibrinogen. Albumins account for most (60% to 80%) of the plasma proteins and are the smallest in size. They are produced by the liver and provide the osmotic pressure needed to draw water from the surrounding tissue fluid into the capillaries. This action is needed to maintain blood volume and pressure. Globulins are grouped into three subtypes: alpha globulins, beta globulins, and gamma globulins. The alpha and beta globulins are produced by the liver and function in transporting lipids and fat-soluble vitamins. Gamma globulins are antibodies produced by lymphocytes (one of the formed elements found in blood and lymphoid tissues) and function in immunity. Fibrinogen, which accounts for only about 4% of the total plasma proteins, is an important clotting factor produced by the liver. During the process of clot formation, fibrinogen is converted into insoluble threads of fibrin. Thus, the fluid from clotted blood, called serum, does not contain fibrinogen but is otherwise identical to plasma.



Principal Function

Binding Characteristics

Serum or Plasma Concentration


Binding and carrier protein; osmotic regulator

Hormones, amino acids, steroids, vitamins, fatty acids

4500–5000 mg/dL


Uncertain; may have a role in inflammation

Trace; rises in inflammation


Trypsin and general protease inhibitor

Proteases in serum and tissue secretions

1.3–1.4 mg/dL


Osmotic regulation; binding and carrier proteina

Hormones, amino acids

Found normally in fetal blood


Inhibitor of serum endoproteases


150–420 mg/dL


Protease inhibitor of intrinsic coagulation system

1:1 binding to proteases

17–30 mg/dL


Transport of copper

Six atoms copper/molecule

15–60 mg/dL

C-reactive protein

Uncertain; has role in tissue inflammation

Complement C1q

<1 mg/dL; rises in inflammation


Precursor to fibrin in hemostasis

200–450 mg/dL


Binding, transport of cell-free hemoglobin

Hemoglobin 1:1 binding

40–180 mg/dL


Binds to porphyrins, particularly heme for heme recycling

1:1 with heme

50–100 mg/dL


Transport of iron

Two atoms iron/molecule

3.0–6.5 mg/dL

Apolipoprotein B

Assembly of lipoprotein particles

Lipid carrier


Precursor to pressor peptide angiotensin II

Proteins, coagulation factors II, VII, IX, X

Blood clotting

20 mg/dL

Antithrombin C, protein C

Inhibition of blood clotting

Insulinlike growth factor I

Mediator of anabolic effects of growth hormone

IGF-I receptor

Steroid hormone-binding globulin

Carrier protein for steroids in bloodstream

Steroid hormones

3.3 mg/dL

Thyroxine-binding globulin

Carrier protein for thyroid hormone in bloodstream

Thyroid hormones

1.5 mg/dL

Transthyretin (thyroid-binding prealbumin)

Carrier protein for thyroid hormone in bloodstream

Thyroid hormones

25 mg/dL

a The function of α-fetoprotein is uncertain, but because of its structural homology to albumin it is often assigned these functions.


Plasma Volume

A number of regulatory mechanisms in the body maintain homeostasis of the plasma volume. If the body should lose water, the remaining plasma becomes excessively concentrated—its osmolality increases. This is detected by osmoreceptors in the hypothalamus, resulting in a sensation of thirst and the release of antidiuretic hormone (ADH) from the posterior pituitary. This hormone promotes water retention by the kidneys, which—together with increased intake of fluids—helps compensate for the dehydration and lowered blood volume. This regulatory mechanism, together with others that influence plasma volume, are very important in maintaining blood pressure.


The Formed Elements of Blood

The formed elements of blood include two types of blood cells: erythrocytes, or red blood cells, and leukocytes, or white blood cells. Erythrocytes are by far the more numerous of the two. A cubic millimeter of blood normally contains 5.1 million to 5.8 million erythrocytes in males and 4.3 million to 5.2 million erythrocytes in females. By contrast, the same volume of blood contains only 5,000 to 9,000 leukocytes.



Leukocytes differ from erythrocytes in several respects. Leukocytes contain nuclei and mitochondria and can move in an amoeboid fashion. Because of their amoeboid ability, leukocytes can squeeze through pores in capillary walls and move to a site of infection, whereas erythrocytes usually remain confined within blood vessels. The movement of leukocytes through capillary walls is referred to as diapedesis or extravasation. White blood cells are almost invisible under the microscope unless they are stained; therefore, they are classified according to their staining properties. Those leukocytes that have granules in their cytoplasm are called granular leukocytes; those without clearly visible granules are called agranular (or nongranular) leukocytes. The stain used to identify white blood cells is usually a mixture of a pink-to-red stain called eosin and a blue-topurple stain (methylene blue), which is called a “basic stain.” Granular leukocytes with pink-staining granules are therefore called eosinophils, and those with blue-staining granules are called basophils. Those with granules that have little affinity for either stain are neutrophils. Neutrophils are the most abundant type of leukocyte, accounting for 50% to 70% of the leukocytes in the blood. Immature neutrophils have sausage-shaped nuclei and are called band cells. As the band cells mature, their nuclei become lobulated, with two to five lobes connected by thin strands. At this stage, the neutrophils are also known as polymorphonuclear leukocytes (PMNs). There are two types of agranular leukocytes: lymphocytes and monocytes. Lymphocytes are usually the second most numerous type of leukocyte; they are small cells with round nuclei and little cytoplasm. Monocytes, by contrast, are the largest of the leukocytes and generally have kidney- or horseshoe-shaped nuclei. In addition to these two cell types, there are smaller numbers of plasma cells, which are derived from lymphocytes. Plasma cells produce and secrete large amounts of antibodies.


Blood cells:


Lymph is tissue fluid that enters the lymphatic vessels. It drains into the venous blood via the thoracic and right lym­phatic ducts. It contains clotting factors and clots on stand­ing in vitro. In most locations, it also contains proteins that have traversed capillary walls and can then return to the blood via the lymph. Nevertheless, its protein content is generally lower than that of plasma, which contains about 7 g/dL, but lymph protein content varies with the region from which the lymph drains. Water-insoluble fats are absorbed from the intestine into the lymphatics, and the lymph in the thoracic duct after a meal is milky because of its high fat content. Lymphocytes also enter the circulation principally through the lymphatics, and there are appreciable numbers of lymphocytes in thoracic duct lymph.



The red blood cells (erythrocytes) carry hemoglobin in the circulation. They are biconcave disks that are manufactured in the bone marrow. In mammals, they lose their nuclei before entering the circulation. In humans, they survive in the circulation for an average of 120 days. The average normal red blood cell count is 5.4 million/μL in men and 4.8 million/μL in women. The number of red cells is also conveniently expressed as the hematocrit, or the percentage of the blood, by volume that is occupied by erythrocytes. Each human red blood cell is about 7.5 μm in diameter and 2 μm thick, and each contains approximately 29 pg of hemoglobin. There are thus about 3 × 1013 red blood cells and about 900 g of hemoglobin in the circulating blood of an adult man. 




Platelets are small, granulated bodies that aggregate at sites of vascular injury. They lack nuclei and are 2–4 μm in diameter. There are about 300,000/μL of circulating blood, and they normally have a half-life of about 4 days. The mega­karyocytes, giant cells in the bone marrow, form platelets by pinching off bits of cytoplasm and extruding them into the cir­culation. Between 60% and 75% of the platelets that have been extruded from the bone marrow are in the circulating blood, and the remainder are mostly in the spleen. Splenectomy causes an increase in the platelet count (thrombocytosis).


Composition of Lymph

Source of Lymph

Protein Content (g/dL)

Choroid plexus


Ciliary body


Skeletal muscle






Gastrointestinal tract










Number Present


Erythrocyte (red blood cell)

Biconcave disc without nucleus; contains hemoglobin; survives 100 to 120 days

4,000,000 to 6,000,000 / mm3

Transports oxygen and carbon dioxide

Leukocytes (white blood cells)


5,000 to 10,000 / mm3

Aid in defense against infections by microorganisms


About twice the size of red blood cells; cytoplasmic granules present; survive 12 hours to 3 days



1. Neutrophil

Nucleus with 2 to 5 lobes; cytoplasmic granules stain slightly pink

54% to 62% of white cells present


2. Eosinophil

Nucleus bilobed; cytoplasmic granules stain red in eosin stain

1% to 3% of white cells present

Helps to detoxify foreign substances; secretes enzymes that dissolve clots; fights parasitic infections

3. Basophil

Nucleus lobed; cytoplasmic granules stain blue in hematoxylin stain

Less than 1% of white cells present

Releases anticoagulant heparin


Cytoplasmic granules not visible; survive 100 to 300 days (some much longer)



1. Monocyte

2 to 3 times larger than red blood cell; nuclear shape varies from round to lobed

3% to 9% of white cells present


2. Lymphocyte

Only slightly larger than red blood cell; nucleus nearly fits cell

25% to 33% of white cells present

Provides specific immune response (including antibodies)

Platelet (thrombocyte)

Cytoplasmic fragment; survives 5 to 9 days

130,000 to 400,000 / mm3

Enables clotting; releases serotonin, which causes vasoconstriction




There are certain molecules on the surfaces of all cells in the body that can be recognized as foreign by the immune system of another individual. These molecules are known as antigens. As part of the immune response, particular lymphocytes secrete a class of proteins called antibodies that bond in a specific fashion with antigens. The specificity of antibodies for antigens is analogous to the specificity of enzymes for their substrates, and of receptor proteins for neurotransmitters and hormones.


ABO System

The distinguishing antigens on other cells are far more varied than the antigens on red blood cells. Red blood cell antigens, however, are of extreme clinical importance because their types must be matched between donors and recipients for blood transfusions. There are several groups of red blood cell antigens, but the major group is known as the ABO system. In terms of the antigens present on the red blood cell surface, a person may be type A (with only A antigens), type B (with only B antigens), type AB (with both A and B antigens), or type O (with neither A nor B antigens). Each person’s blood type-A, B, or O-denotes the antigens present on the red blood cell surface, which are the products of the genes (located on chromosome number 9) that code for these antigens.


Each person inherits two genes (one from each parent) that control the production of the ABO antigens. The genes for A or B antigens are dominant to the gene for O. The O gene is recessive, simply because it doesn’t code for either the A or the B red blood cell antigens. The genes for A and B are often shown as I A and I B  and the recessive gene for O is shown as the lowercase i. A person who is type A, therefore, may have inherited the A gene from each parent (may have the genotype I A I A ), or the A gene from one parent and the O gene from the other parent (and thus have the genotype I A i). Likewise, a person who is type B may have the genotype I B I B or I B i. It follows that a type O person inherited the O gene from each parent (has the genotype ii), whereas a type AB person inherited the A gene from one parent and the B gene from the other (there is no dominant-recessive relationship between A and B). The immune system exhibits tolerance to its own red blood cell antigens. People who are type A, for example, do not produce anti-A antibodies. Surprisingly, however, they do make antibodies against the B antigen and, conversely, people with blood type B make antibodies against the A antigen.  This is believed to result from the fact that antibodies made in response to some common bacteria cross-react with the A or B antigens. People who are type A, therefore, acquire antibodies that can react with B antigens by exposure to these bacteria, but they do not develop anti bodies that can react with A antigens because tolerance mechanisms prevent this. People who are type AB develop tolerance to both of these antigens, and thus do not produce either anti-A or anti-B antibodies. Those who are type O, by contrast, do not develop tolerance to either antigen; therefore, they have both anti-A and anti-B antibodies in their plasma.


Transfusion Reactions

Before transfusions are performed, a major crossmatch is made by mixing serum from the recipient with blood cells from the donor. If the types do not match—if the donor is type A, for example, and the recipient is type B—the recipient’s antibodies attach to the donor’s red blood cells and form bridges that cause the cells to clump together, or agglutinate. Because of this agglutination reaction, the A and B antigens are sometimes called agglutinogens, and the antibodies against them are called agglutinins. Transfusion errors that result in such agglutination can lead to blockage of small blood vessels and cause hemolysis (rupture of red blood cells), which may damage the kidneys and other organs. In emergencies, type O blood has been given to people who are type A, B, AB, or O. Because type O red blood cells lack A and B antigens, the recipient’s antibodies cannot cause agglutination of the donor red blood cells. Type O is, therefore, a universal donor —but only as long as the volume of plasma donated is small, since plasma from a type O person would agglutinate type A, type B, and type AB red blood cells. Likewise, type AB people are universal recipients because they lack anti-A and anti-B antibodies, and thus cannot agglutinate donor red blood cells. (Donor plasma could agglutinate recipient red blood cells if the transfusion volume were too large.) Because of the dangers involved, use of the universal donor and recipient concept is strongly discouraged in practice.


Rh Factor

Another group of antigens found on the red blood cells of most people is the Rh factor (named for the rhesus monkey, in which these antigens were first discovered). There are a number of different antigens in this group, but one stands out because of its medical significance. This Rh antigen is termed D, and is often indicated as Rho(D). If this Rh antigen

is present on a person’s red blood cells, the person is Rh positive; if it is absent, the person is Rh negative. The Rh-positive condition is by far the more common (with a frequence of 85% in the Caucasian population, for example). The Rh factor is of particular significance when Rh- negative mothers give birth to Rh-positive babies. The fetal and maternal blood are normally kept separate across the placenta, and so the Rh-negative mother is not usually exposed to the Rh antigen of the fetus during the pregnancy. At the time of birth, however, a variable degree of exposure may occur, and the mother’s immune system may become sensitized and produce antibodies against the Rh antigen. This does not always occur, however, because the exposure may be minimal and because Rh-negative women vary in their sensitivity to the Rh factor. If the woman does produce antibodies against the Rh factor, these antibodies could cross the placenta in subsequent pregnancies and cause hemolysis of the Rh-positive red blood cells of the fetus. Therefore, the baby could be born anemic with a condition called erythroblastosis fetalis, or hemolytic disease of the newborn. Erythroblastosis fetalis can be prevented by injecting the Rh-negative mother with an antibody preparation against the Rh factor (a trade name for this preparation is RhoGAM—the GAM is short for gamma globulin, the class of plasma proteins in which antibodies are found) within 72 hours after the birth of each Rh-positive baby. This is a type of passive immunization in which the injected antibodies inactivate the Rh antigens and thus prevent the mother from becoming actively immunized to them. Some physicians now give RhoGAM throughout the Rh-positive pregnancy of any Rh-negative woman.





More than 50 important substances that cause or affect blood coagulation have been found in the blood and in the tissues—some that promote coagulation, called procoagulants, and others that inhibit coagulation, called anticoagulants. Whether blood will coagulate depends on the balance between these two groups of substances. In the blood stream, the anticoagulants normally predominate, so the blood does not coagulate while it is circulating in the blood vessels. However, when a vessel is ruptured, procoagulants from the area of tissue damage become “activated” and override the anticoagulants, and then a clot does develop.

Clotting takes place in three essential steps:

1. In response to rupture of the vessel or damage to the blood itself, a complex cascade of chemical reactions occurs in the blood involving more than a dozen blood coagulation factors. The net result is formation of a complex of activated substances collectively called prothrombin activator.

2. The prothrombin activator catalyzes conversion of prothrombin into thrombin.

3. The thrombin acts as an enzyme to convert fibrinogen into fibrin fibers that enmesh platelets, blood cells, and plasma to form the clot.



These mechanisms are set into play by (1) trauma to the vascular wall and adjacent tissues, (2) trauma to the blood, or (3) contact of the blood with damaged endothelial cells or with collagen and other tissue elements outside the blood vessel. In each instance, this leads to the formation of prothrombin activator, which then causes prothrombin conversion to thrombin and all the subsequent clotting steps. Prothrombin activator is generally considered to be formed in two ways, although, in reality, the two ways interact constantly with each other: (1) by the extrinsic pathway that begins with trauma to the vascular wall and surrounding tissues and (2) by the intrinsic pathway that begins in the blood. In both the extrinsic and the intrinsic pathways, a series of different plasma proteins called blood-clotting factors plays a major role. Most of these proteins are inactive forms of proteolytic enzymes. When converted to the active forms, their enzymatic actions cause the successive, cascading reactions of the clotting process. Most of the clotting factors, which are designated by Roman numerals. To indicate the activated form of the factor, a small letter “a” is added after the Roman numeral, such as Factor VIIIa to indicate the activated state of Factor VIII.


Extrinsic Pathway for Initiating Clotting

The extrinsic pathway for initiating the formation of prothrombin activator begins with a traumatized vascular wall or traumatized extravascular tissues that come in contact with the blood. This condition leads to the following steps:

1. Release of tissue factor. Traumatized tissue releases a complex of several factors called tissue factor or tissue thromboplastin. This factor is composed especially of phospholipids from the membranes of the tissue plus a lipoprotein complex that functions mainly as a proteolytic enzyme.

2. Activation of Factor X—role of Factor VII and tissue factor. The lipoprotein complex of tissue factor further complexes with blood coagulation Factor VII and, in the presence of calcium ions, acts enzymatically on Factor X to form activated Factor X (Xa).

3. Effect of Xa to form prothrombin activator—role of Factor V. The activated Factor X combines immediately with tissue phospholipids that are part of tissue factors or with additional phospholipids released from platelets, as well as with Factor V, to form the complex called prothrombin activator. Within a few seconds, in the presence of Ca++, prothrombin is split to form thrombin, and the clotting process proceeds as already explained. At first, the Factor V in the prothrombin activator complex is inactive, but once clotting begins and thrombin begins to form, the proteolytic action of thrombin activates Factor V. This activation then becomes an additional strong accelerator of prothrombin activation. Thus, in the final prothrombin activator complex, activated Factor X is the actual protease that causes splitting of prothrombin to form thrombin; activated Factor V greatly accelerates this protease activity, and platelet phospholipids act as a vehicle that further accelerates the process. Note especially the positive feedback effect of thrombin, acting through Factor V, to accelerate the entire process once it begins.


Intrinsic Pathway for Initiating Clotting

The second mechanism for initiating formation of prothrombin activator, and therefore for initiating clotting, begins with trauma to the blood or exposure of the blood to collagen from a traumatized blood vessel wall. Then the process continues through the series of cascading reactions.

1. Blood trauma causes (1) activation of Factor XII and (2) release of platelet phospholipids. Trauma to the blood or exposure of the blood to vascular wall collagen alters two important clotting factors in the blood: Factor XII and the platelets. When Factor XII is disturbed, such as by coming into contact with collagen or with a wettable surface such as glass, it takes on a new molecular configuration that converts it into a proteolytic enzyme called “activated Factor XII.” Simultaneously, the blood trauma also damages the platelets because of adherence to either collagen or a wettable surface (or by damage in other ways), and this releases platelet phospholipids that contain the lipoprotein called platelet factor 3, which also plays a role in subsequent clotting reactions.

2. Activation of Factor XI. The activated Factor XII acts enzymatically on Factor XI to activate this factor as well, which is the second step in the intrinsic pathway. This reaction also requires highmolecular-weight kininogen and is accelerated by prekallikrein.

3. Activation of Factor IX by activated Factor XI. The activated Factor XI then acts enzymatically on Factor IX to activate this factor as well.

4. Activation of Factor X—role of Factor VIII. The activated Factor IX, acting in concert with activated Factor VIII and with the platelet phospholipids and Factor III from the traumatized platelets, activates Factor X. It is clear that when either Factor VIII or platelets are in short supply, this step is deficient. Factor VIII is the factor that is missing in a person who has classic hemophilia, for which reason it is called antihemophilic factor. Platelets are the clotting factor that is lacking in the bleeding disease called thrombocytopenia.

5. Action of activated Factor X to form prothrombin activator—role of Factor V. This step in the intrinsic pathway is the same as the last step in the extrinsic pathway. That is, activated Factor X combines with Factor V and platelet or tissue phospholipids to form the complex called prothrombin activator. The prothrombin activator in turn initiates within seconds the cleavage of prothrombin to form thrombin, thereby setting into motion the final clotting process, as described earlier.


Interaction between the Extrinsic and Intrinsic Pathways

It is clear from the schemas of the intrinsic and extrinsic systems that after blood vessels rupture, clotting occurs by both pathways simultaneously. Tissue factor initiates the extrinsic pathway, whereas contact of Factor XII and platelets with collagen in the vascular wall   initiates the intrinsic pathway.


An especially important difference between the extrinsic and intrinsic pathways is that the extrinsic pathway can be explosive; once initiated, its speed of completion to the final clot is limited only by the amount of tissue factor released from the traumatized tissues and by the quantities of Factors X, VII, and V in the blood. With severe tissue trauma, clotting can occur in as little as 15 seconds. The intrinsic pathway is much slower to proceed, usually requiring 1 to 6 minutes to cause clotting.


Clotting factors

Clotting Factor



Factor I


Factor II

Tissue factor

Factor III; tissue thromboplastin


Factor IV

Factor V

Proaccelerin; labile factor; Ac-globulin (Ac-G)

Factor VII

Serum prothrombin conversion accelerator (SPCA); proconvertin; stable factor

Factor VIII

Antihemophilic factor (AHF); antihemophilic globulin (AHG); antihemophilic factor A

Factor IX

Plasma thromboplastin component (PTC); Christmas factor; antihemophilic factor B. This factor named with Stephen Christmas who was first identified with Christmas disease in 1952.

Factor X

Stuart factor; Stuart-Prower factor

Factor XI

Plasma thromboplastin antecedent (PTA); antihemophilic factor C

Factor XII

Hageman factor

Factor XIII

Fibrin-stabilizing factor


Fletcher factor

High-molecular-weight kininogen

Fitzgerald factor; HMWK (high-molecular-weight kininogen)


Closed wall formation due to its aggregation

Von-Willebrand factor

It binds to factor VIII and prevent its degradation. It also binds to collagen of vascular injury site and promotes platelets attachment and aggregation.






Deficiency of Factor:

Clinical Syndrome




Depletion during pregnancy with premature separation of placenta; also congenital (rare)


Hypoprothrombinemia (hemorrhagic tendency in liver disease)

Decreased hepatic synthesis, usually secondary to vitamin K deficiency








Hemophilia A (classic hemophilia)

Congenital defect due to various abnormalities of the gene on X chromosome that codes for factor VIII; disease is therefore inherited as a sex-linked characteristic


Hemophilia B (Christmas disease)



Stuart-Prower factor deficiency



PTA deficiency



Hageman trait




When a sharp-pointed knife is used to pierce the tip of the finger or lobe of the ear, bleeding ordinarily lasts for 1 to 6 minutes. The time depends largely on the depth of the wound and the degree of hyperemia in the finger or ear lobe at the time of the test. Lack of any one of several of the clotting factors can prolong the bleeding time, but it is especially prolonged by lack of platelets.



Many methods have been devised for determining blood clotting times. The one most widely used is to collect blood in a chemically clean glass test tube and then to tip the tube back and forth about every 30 seconds until the blood has clotted. By this method, the normal clotting time is 6 to 10 minutes. Procedures using multiple test tubes have also been devised for determining clotting time more accurately. Unfortunately, the clotting time varies widely, depending on the method used for measuring it, so it is no longer used in many clinics. Instead, measurements of the clotting factors themselves are made, using sophisticated chemical procedures.



Prothrombin time gives an indication of the concentration of prothrombin in the blood.




The heart is a muscular organ enclosed in a protective fibrous sac, the pericardium, and located in the chest. A fibrous layer is also closely affixed to the heart and is called the epicardium. The extremely narrow space between the pericardium and the epicardium is filled with a watery fluid that serves as a lubricant as the heart moves within the sac. The wall of the heart, the myocardium, is composed primarily of cardiac muscle cells. The inner surface of the cardiac chambers, as well as the inner wall of all blood vessels, is lined by a thin layer of cells known as endothelial cells, or endothelium. As noted earlier, the human heart is divided into right and left halves, each consisting of an atrium and a ventricle. The two ventricles are separated by a muscular wall, the interventricular septum. Located between the atrium and ventricle in each half of the heart are the one-way atrioventricular (AV) valves, which permit blood to flow from atrium to ventricle but not backward from ventricle to atrium. The right AV valve is called the tricuspid valve because it has three fibrous flaps, or cusps. The left AV valve has two flaps and is therefore called the bicuspid valve. Its resemblance to a bishop’s headgear (a “mitre”) has earned the left AV valve another commonly used name, mitral valve. The opening and closing of the AV valves are passive processes resulting from pressure differences across the valves. When the blood pressure in an atrium is greater than in the corresponding ventricle, the valve is pushed open and blood flows from atrium to ventricle. In contrast, when a contracting ventricle achieves an internal pressure greater than that in its connected atrium, the AV valve between them is forced closed. Therefore, blood does not normally move back into the atria but is forced into the pulmonary trunk from the right ventricle and into the aorta from the left ventricle.


To prevent the AV valves from being pushed up and opening backward into the atria when the ventricles are contracting (a condition called prolapse), the valves are fastened to muscular projections (papillary muscles) of the ventricular walls by fibrous strands (chordae tendineae). The papillary muscles do not open or close the valves. They act only to limit the valves’ movements and prevent the backward flow of blood. Injury and disease of these tendons or muscles can lead to prolapse. The openings of the right ventricle into the pulmonary trunk and of the left ventricle into the aorta also contain valves, the pulmonary and aortic valves, respectively. These valves are also referred to as the semilunar valves, due to the half-moon shape of the cusps. These valves allow blood to flow into the arteries during ventricular contraction but prevent blood from moving in the opposite direction during ventricular relaxation. Like the AV valves, they act in a passive manner. Whether they are open or closed depends upon the pressure differences across them. Another important point concerning the heart valves is that, when open, they offer very little resistance to flow. Consequently, very small pressure differences across them suffice to produce large flows. In disease states, however, a valve may become narrowed or not open fully so that it offers a high resistance to flow even when open. In such a state, the contracting cardiac chamber must produce an unusually high pressure to cause flow across the valve. There are no valves at the entrances of the superior and inferior venae cavae (singular, vena cava) into the right atrium, and of the pulmonary veins into the left atrium. However, atrial contraction pumps very little blood back into the veins because atrial contraction constricts their sites of entry into the atria, greatly increasing the resistance to backflow.

Pulmonary and Systemic Circulations

Blood whose oxygen content has become partially depleted and whose carbon dioxide content has increased as a result of tissue metabolism returns to the right atrium. This blood then enters the right ventricle, which pumps it into the pulmonary trunk and pulmonary arteries. The pulmonary arteries branch to transport blood to the lungs, where gas exchange occurs between the lung capillaries and the air sacs (alveoli) of the lungs. Oxygen diffuses from the air to the capillary blood, while carbon dioxide diffuses in the opposite direction.


The blood that returns to the left atrium by way of the pulmonary veins is therefore enriched in oxygen and partially depleted of carbon dioxide. The path of blood from the heart (right ventricle), through the lungs, and back to the heart (left atrium) completes one circuit: the pulmonary circulation. Oxygen-rich blood in the left atrium enters the left ventricle and is pumped into a very large, elastic artery-the aorta. The aorta ascends for a short distance, makes a U-turn, and then descends through the thoracic (chest) and abdominal cavities. Arterial branches from the aorta supply oxygen-rich blood to all of the organ systems and are thus part of the systemic circulation.


As a result of cellular respiration, the oxygen concentration is lower and the carbon dioxide concentration is higher in the tissues than in the capillary blood. Blood that drains from the tissues into the systemic veins is thus partially depleted of oxygen and increased in carbon dioxide content. These veins ultimately empty into two large veins—the superior and inferior venae cavae —that return the oxygen-poor blood to the right atrium. This completes the systemic circulation: from the heart (left ventricle), through the organ systems, and back to the heart (right atrium). The numerous small muscular arteries and arterioles of the systemic circulation present greater resistance to blood flow than that in the pulmonary circulation. Despite the differences in resistance, the rate of blood flow through the systemic circulation must be matched to the flow rate of the pulmonary circulation. Because the amount of work performed by the left ventricle is greater (by a factor of 5 to 7) than that performed by the right ventricle, it is not surprising that the muscular wall of the left ventricle is thicker (8 to 10 mm) than that of the right ventricle (2 to 3 mm).



Late in diastole, the mitral (bicuspid) and tricuspid valves between the atria and ventricles (atrioventricular [AV] valves) are open and the aortic and pulmonary valves are closed. Blood flows into the heart throughout diastole, filling the atria and ventricles. The rate of filling declines as the ventri­cles become distended and, especially when the heart rate is low, the cusps of the AV valves drift toward the closed posi­tion. The pressure in the ventricles remains low. About 70% of the ventricular filling occurs passively during diastole.



Contraction of the atria propels some additional blood into the ventricles. Contraction of the atrial muscle narrows the orifices of the superior and inferior vena cava and pulmonary veins, and the inertia of the blood moving toward the heart tends to keep blood in it. However, despite these inhibitory influences, there is some regurgitation of blood into the veins.


At the start of ventricular systole, the AV valves close. Ven­tricular muscle initially shortens relatively little, but intra­ventricular pressure rises sharply as the myocardium presses on the blood in the ventricle. This period of isovolumetric (isovolumic, isometric) ventricular con­traction lasts about 0.05 s, until the pressures in the left and right ventricles exceed the pressures in the aorta (80 mm Hg; 10.6 kPa) and pulmonary artery (10 mm Hg) and the aortic and pulmonary valves open. During isovolumetric contrac­tion, the AV valves bulge into the atria, causing a small but sharp rise in atrial pressure.  When the aortic and pulmonary valves open, the phase of ventricular ejection begins. Ejection is rapid at first, slowing down as systole progresses. The intraventricular pressure rises to a maximum and then declines somewhat before ventricular systole ends. Peak pressures in the left and right ventricles are about 120 and 25 mm Hg, respectively. Late in systole, pressure in the aorta actually exceeds that in the left ventricle, but for a short period momentum keeps the blood moving forward. The AV valves are pulled down by the contractions of the ventricular muscle, and atrial pressure drops. The amount of blood ejected by each ventricle per stroke at rest is 70–90 mL. The end-diastolic ventricular volume is about 130 mL. Thus, about 50 mL of blood remains in each ventricle at the end of systole (end-systolic ventricular volume), and the ejection fraction, the percentage of the end-diastolic ventricular vol­ume that is ejected with each stroke, is about 65%. The ejec­tion fraction is a valuable index of ventricular function. It can be measured by injecting radionuclide-labeled red blood cells and imaging the cardiac blood pool at the end of diastole and the end of systole (equilibrium radionuclide angiocardiogra­phy), or by computed tomography.



Once the ventricular muscle is fully contracted, the already falling ventricular pressures drop more rapidly. This is the period of protodiastole, which lasts about 0.04 s. It ends when the momentum of the ejected blood is overcome and the aortic and pulmonary valves close, setting up transient vibrations in the blood and blood vessel walls. After the valves are closed, pressure continues to drop rapidly during the period of iso­volumetric ventricular relaxation. Isovolumetric relaxation ends when the ventricular pressure falls below the atrial pres­sure and the AV valves open, permitting the ventricles to fill. Filling is rapid at first, then slows as the next cardiac contrac­tion approaches. Atrial pressure continues to rise after the end of ventricular systole until the AV valves open, then drops and slowly rises again until the next atrial systole.


Events of the cardiac cycle at a heart rate of 75 beats/min. The phases of the cardiac cycle identified by the numbers at the bottom are as follows: 1, atrial systole; 2, isovolumetric ventricular contraction; 3, ventricular ejection; 4, isovolumetric ventricular relaxation; 5, ventricular filling. Note that late in systole, aortic pressure actually exceeds left ventricular pressure. However, the momentum of the blood keeps it flowing out of the ventricle for a short period. The pressure relationships in the right ventricle and pulmonary artery are similar. Atr. syst., atrial systole; ventric. syst., ventricular systole.

Cardiac cycle is the sequence of electrical and mechanical events that repeats with every heartbeat.  There are two phases namely diastolic phase and systolic phase. 



Although events on the two sides of the heart are similar, they are somewhat asynchronous. Right atrial systole precedes left atrial systole, and contraction of the right ventricle starts after that of the left. However, since pulmonary arterial pressure is lower than aortic pressure, right ventricular ejection begins before that of the left. During expiration, the pulmonary and aortic valves close at the same time; but during inspiration, the aortic valve closes slightly before the pulmo­nary. The slower closure of the pulmonary valve is due to lower impedance of the pulmonary vascular tree. When measured over a period of minutes, the outputs of the two ventricles are, of course, equal, but transient differences in output during the respiratory cycle occur in normal individuals.



Cardiac muscle has the unique property of contracting and repolarizing faster when the heart rate is high (see Chapter 5), and the duration of systole decreases from 0.27 s at a heart rate of 65 beats/min to 0.16 s at a rate of 200 beats/min. The reduced time interval is mainly due to a

decrease in the duration of systolic ejection. However, the duration of systole is much more fixed than that of diastole, and when the heart rate is increased, diastole is shortened to a much greater degree. For example, at a heart rate of 65 beats/min, the duration of diastole is 0.62 s, whereas at a heart rate of 200 beats/min, it is only 0.14 s. This fact has important physi­ologic and clinical implications. It is during diastole that the heart muscle rests, and coronary blood flow to the subendo­cardial portions of the left ventricle occurs only during dias­tole. Furthermore, most of the ventricular filling occurs in diastole. At heart rates up to about 180 beats/min, filling is adequate as long as there is ample venous return, and cardiac output per minute is increased by an increase in rate. However, at very high heart rates, filling may be compro­mised to such a degree that cardiac output per minute falls.


Because it has a prolonged action potential, cardiac mus­cle cannot contract in response to a second stimulus until near the end of the initial contraction. Therefore, cardiac muscle cannot be tetanized like skeletal muscle. The highest rate at which the ventricles can contract is theoreti­cally about 400/min, but in adults the AV node will not con­duct more than about 230 impulses/min because of its long refractory period. A ventricular contraction rate of more than 230/min is seen only in paroxysmal ventricular tachycardia.


Exact measurement of the duration of isovolumetric ven­tricular contraction is difficult in clinical situations, but it is relatively easy to measure the duration of total electrome­chanical systole (QS2), the preejection period (PEP), and the left ventricular ejection time (LVET) by recording the ECG, phonocardiogram, and carotid pulse simultaneously. QS2 is the period from the onset of the QRS complex to the closure of the aortic valves, as determined by the onset of the second heart sound. LVET is the period from the beginning of the carotid pressure rise to the dicrotic notch (see below). PEP is the difference between QS2 and LVET and represents the time for the electrical as well as the mechanical events that precede systolic ejection. The ratio PEP/LVET is normally about 0.35, and it increases without a change in QS2 when left ventricular performance is compromised in a variety of cardiac diseases.



The blood forced into the aorta during systole not only moves the blood in the vessels forward but also sets up a pressure wave that travels along the arteries. The pressure wave expands the arterial walls as it travels, and the expansion is palpable as the pulse. The rate at which the wave travels, which is inde­pendent of and much higher than the velocity of blood flow, is about 4 m/s in the aorta, 8 m/s in the large arteries, and 16 m/s in the small arteries of young adults. Consequently, the pulse is felt in the radial artery at the wrist about 0.1 s after the peak of systolic ejection into the aorta. With advanc­ing age, the arteries become more rigid, and the pulse wave moves faster.


The strength of the pulse is determined by the pulse pres­sure and bears little relation to the mean pressure. The pulse is weak (“thready”) in shock. It is strong when stroke volume is large; for example, during exercise or after the administra­tion of histamine. When the pulse pressure is high, the pulse waves may be large enough to be felt or even heard by the indi­vidual (palpitation, “pounding heart”). When the aortic valve is incompetent (aortic regurgitation), the pulse is particularly strong, and the force of systolic ejection may be sufficient to make the head nod with each heartbeat. The pulse in aortic regurgitation is called a Corrigan or water-hammer pulse.  The dicrotic notch, a small oscillation on the falling phase of the pulse wave caused by vibrations set up when the aortic valve snaps shut, is visible if the pressure wave is recorded but is not palpable at the wrist. The pulmonary artery pressure curve also has a dicrotic notch produced by the closure of the pulmonary valves.



Atrial pressure rises during atrial systole and continues to rise during isovolumetric ventricular contraction when the AV valves bulge into the atria. When the AV valves are pulled down by the contracting ventricular muscle, pressure falls rap­idly and then rises as blood flows into the atria until the AV valves open early in diastole. The return of the AV valves to their relaxed position also contributes to this pressure rise by reducing atrial capacity. The atrial pressure changes are trans­mitted to the great veins, producing three characteristic waves in the record of jugular pressure. The a wave is due to atrial systole. As noted above, some blood regurgi­tates into the great veins when the atria contract. In addition, venous inflow stops, and the resultant rise in venous pressure contributes to the  a wave. The c wave is the transmitted mani­festation of the rise in atrial pressure produced by the bulg­ing of the tricuspid valve into the atria during isovolumetric ventricular contraction. The v wave mirrors the rise in atrial pressure before the tricuspid valve opens during diastole. The jugular pulse waves are superimposed on the respiratory fluctuations in venous pressure. Venous pressure falls during inspiration as a result of the increased negative intrathoracic pressure and rises again during expiration.



Two sounds are normally heard through a stethoscope dur­ing each cardiac cycle. The first is a low, slightly prolonged “lub” (first sound), caused by vibrations set up by the sudden closure of the AV valves at the start of ventricular systole. The second is a shorter, high-pitched “dup” (second sound), caused by vibrations associated with clo­sure of the aortic and pulmonary valves just after the end of ventricular systole. A soft, low-pitched third sound is heard about one-third of the way through diastole in many normal young individuals. It coincides with the period of rapid ven­tricular filling and is probably due to vibrations set up by the inrush of blood. A fourth sound can sometimes be heard immediately before the first sound when atrial pressure is high or the ventricle is stiff in conditions such as ventricular hypertrophy. It is due to ventricular filling and is rarely heard in normal adults. The first sound has a duration of about 0.15 s and a frequency of 25–45 Hz. It is soft when the heart rate is low, because the ventricles are well filled with blood and the leaf­lets of the AV valves float together before systole. The second sound lasts about 0.12 s, with a frequency of 50 Hz. It is loud and sharp when the diastolic pressure in the aorta or pul­monary artery is elevated, causing the respective valves to shut briskly at the end of systole. The interval between aortic and pulmonary valve closure during inspiration is frequently long enough for the second sound to be reduplicated (physi­ologic splitting of the second sound). Splitting also occurs in various diseases. The third sound, when present, has a dura­tion of 0.1 s.



Murmurs, or bruits, are abnormal sounds heard in various parts of the vascular system. The two terms are used inter­changeably, though “murmur” is more commonly used to denote noise heard over the heart than over blood vessels. Blood flow is laminar, non­turbulent, and silent up to a critical velocity; above this veloc­ity (such as beyond an obstruction), blood flow is turbulent and creates sounds. Blood flow speeds up when an artery or a heart valve is narrowed.  Examples of vascular sounds outside the heart are the bruit heard over a large, highly vascular goiter, the bruit heard over a carotid artery when its lumen is narrowed and distorted by atherosclerosis, and the murmurs heard over an aneu­rysmal dilation of one of the large arteries, an arteriovenous (A-V) fistula, or a patent ductus arteriosus. The major—but certainly not the only—cause of cardiac murmurs is disease of the heart valves. When the orifice of a valve is narrowed (stenosis), blood flow through it is acceler­ated and turbulent. When a valve is incompetent, blood flows through it backward (regurgitation), again through a narrow orifice that accelerates flow. The timing (systolic or diastolic) of a murmur due to any particular valve can be predicted from a knowledge of the mechanical events of the cardiac cycle. Murmurs due to disease of a particular valve can generally be heard best when the stethoscope is directly over the valve. There are also other aspects of the duration, character, accentuation, and transmission of the sound that help locate its origin in one valve or another. One of the loud­est murmurs is that produced when blood flows backward in diastole through a hole in a cusp of the aortic valve. Most murmurs can be heard only with the aid of the stethoscope, but this high-pitched musical diastolic murmur is sometimes audible to the unaided ear several feet from the patient. In patients with congenital interventricular septal defects, flow from the left to the right ventricle causes a systolic mur­mur. Soft murmurs may also be heard in patients with inter­atrial septal defects, although they are not a constant finding. Soft systolic murmurs are also common in individuals, especially children, who have no cardiac disease. Systolic mur­murs are also heard in anemic patients as a result of the low vis­cosity of the blood and associated rapid flow.


Heartbeat Coordination

The heart is a dual pump in that the left and right sides of the heart pump blood separately—but simultaneously—into the systemic and pulmonary vessels. Efficient pumping of blood requires that the atria contract first, followed almost immediately by the ventricles. Contraction of cardiac muscle, like that of skeletal muscle and many smooth muscles, is triggered by depolarization of the plasma membrane. Gap junctions interconnect myocardial cells and allow action potentials to spread from one cell to another. The initial excitation of one cardiac cell therefore eventually results in the excitation of all cardiac cells. This initial depolarization normally arises in a small group of conducting-system cells called the sinoatrial (SA) node, located in the right atrium near the entrance of the superior vena cava. The action potential then spreads from the SA node throughout the atria and then into and throughout the ventricles.


Sequence of Excitation

The SA node is normally the pacemaker for the entire heart. Its depolarization generates the action potential that leads to depolarization of all other cardiac muscle cells. As we will see later, electrical excitation of the heart is coupled with contraction of cardiac muscle. Therefore, the discharge rate of the SA node determines the heart rate, the number of times the heart contracts per minute.  The action potential initiated in the SA node spreads throughout the myocardium, passing from cell to cell by way of gap junctions. Depolarization first spreads through the muscle cells of the atria, with conduction rapid enough that the right and left atria contract at essentially the same time. The spread of the action potential to the ventricles involves a more complicated conducting system, which consists of modified cardiac cells that have lost contractile capability but that conduct action potentials with low resistance. The link between atrial depolarization and ventricular depolarization is a portion of the conducting system called the atrioventricular (AV) node, located at the base of the right atrium. The action potential is conducted relatively rapidly from the SA node to the AV node through internodal pathways. The AV node is an elongated structure with a particularly important characteristic: The propagation of action potentials through the AV node is relatively slow (requiring approximately 0.1 sec). This delay allows atrial contraction to be completed before ventricular excitation occurs.


After the AV node has become excited, the action potential propagates down the interventricular septum. This pathway has conducting-system fibers called the bundle of His (pronounced “hiss”), or atrioventricular bundle. The fibers were identified by Wilhelm His in 1893. The AV node and the bundle of His constitute the only electrical connection between the atria and the ventricles. Except for this pathway, the atria are separated from the ventricles by a layer of nonconducting connective tissue. Within the interventricular septum, the bundle of His divides into right and left bundle branches, which separate at the bottom (apex) of the heart and enter the walls of both ventricles. These pathways are composed of Purkinje fibers, which are largediameter, rapidly conducting cells connected by low-resistance gap junctions. The branching network of Purkinje fibers conducts the action potential rapidly to myocytes throughout the ventricles. The rapid conduction along the Purkinje fibers and the diffuse distribution of these fibers cause depolarization of all right and left ventricular cells to occur nearly simultaneously and ensure a single coordinated contraction. Actually, though, depolarization and contraction do begin slightly earlier in the apex of the ventricles and then spread upward. The result is an efficient contraction that moves blood toward the exit valves, like squeezing a tube of toothpaste from the bottom up.


In the discussion thus far of the genesis and transmission of the cardiac impulse through the heart, we have noted that the impulse normally arises in the sinus node. In some abnormal conditions, this is not the case. Other parts of the heart can also exhibit intrinsic rhythmical excitation in the same way that the sinus nodal fibers do; this capability is particularly true of the A-V nodal and Purkinje fibers. The A-V nodal fibers, when not stimulated from some outside source, discharge at an intrinsic rhythmical rate of 40 to 60 times per minute, and the Purkinje fibers discharge at a rate somewhere between 15 and 40 times per minute. These rates are in contrast to the normal rate of the sinus node of 70 to 80 times per minute.


The discharge rate of the sinus node is considerably faster than the natural self-excitatory discharge rate of either the A-V node or the Purkinje fibers. Purkinje J.E., modified muscle fiber in subendothelial region in 1839. Each time the sinus node discharges, its impulse is conducted into both the A-V node and the Purkinje fibers, also discharging their excitable membranes. However, the sinus node discharges again before either the A-V node or the Purkinje fibers can reach their own thresholds for self-excitation. Therefore, the new impulse from the sinus node discharges both the A-V node and the Purkinje fibers before self-excitation can occur in either of these sites. Thus, the sinus node controls the beat of the heart because its rate of rhythmical discharge is faster than that of any other part of the heart. Therefore, the sinus node is almost always the pacemaker of the normal heart.


Abnormal Pacemakers -“Ectopic” Pacemaker. Occasionally some other part of the heart develops a rhythmical discharge rate that is more rapid than that of the sinus node. For instance, this development sometimes occurs in the A-V node or in the Purkinje fibers when one of these becomes abnormal. In either case, the pacemaker of the heart shifts from the sinus node to the A-V node or to the excited Purkinje fibers. Under rarer conditions, a place in the atrial or ventricular muscle develops excessive excitability and becomes the pacemaker.


A pacemaker elsewhere than the sinus node is called an “ectopic” pacemaker. An ectopic pacemaker causes an abnormal sequence of contraction of the different parts of the heart and can cause significant debility of heart pumping. Another cause of shift of the pacemaker is blockage of transmission of the cardiac impulse from the sinus node to the other parts of the heart. The new pacemaker then occurs most frequently at the A-V node or in the penetrating portion of the A-V bundle on the way to the ventricles. When A-V block occurs—that is, when the cardiac impulse fails to pass from the atria into the ventricles through the A-V nodal and bundle system—the atria continue to beat at the normal rate of rhythm of the sinus node, while a new pacemaker usually develops in the Purkinje system of the ventricles and drives the ventricular muscle at a new rate somewhere between 15 and 40 beats per minute. After sudden A-V bundle block, the Purkinje system does not begin to emit its intrinsic rhythmical impulses until 5 to 20 seconds later because, before the blockage, the Purkinje fibers had been “overdriven” by the rapid sinus impulses and, consequently, are in a suppressed state. During these 5 to 20 seconds, the ventricles fail to pump blood, and the person faints after the first 4 to 5 seconds because of lack of blood flow to the brain. This delayed pickup of the heartbeat is called Stokes-Adams syndrome. If the delay period is too long, it can lead to death Robert Adam and William Stokes identified the syndrome.

Transmission of the cardiac impulse through the heart, showing the time of appearance (in fractions of a second after initial appearance at the sinoatrial node) in different parts of the heart. A-V, atrioventricular; S-A, sinoatrial.


The Electrocardiogram

The body is a good conductor of electricity because tissue fluids have a high concentration of ions that move (creating a current) in response to potential differences. Potential differences generated by the heart are conducted to the body surface, where they can be recorded by surface electrodes placed on the skin. The recording thus obtained is called an electrocardiogram ( ECG or EKG ); the recording device is called an electrocardiograph. Each cardiac cycle produces three distinct ECG waves, designated P, QRS, and T. Note that the ECG is not a recording of action potentials, but it does result from the production and conduction of action potentials in the heart. The correlation of an action potential produced in the ventricles to the waves of the ECG. This figure shows that the spread of depolarization through the ventricles (indicated by the QRS, described shortly) corresponds to the action potential, and thus to contraction of the ventricles. The spread of depolarization through the atria causes a potential difference that is indicated by an upward deflection of the ECG line. When about half the mass of the atria is depolarized, this upward deflection reaches a maximum value because the potential difference between the depolarized and unstimulated portions of the atria is at a maximum. When the entire mass of the atria is depolarized, the ECG returns to baseline because all regions of the atria have the same polarity. The spread of atrial depolarization thereby creates the P wave. Conduction of the impulse into the ventricles similarly creates a potential difference that results in a sharp upward deflection of the ECG line, which then returns to the baseline as the entire mass of the ventricles becomes depolarized. The spread of the depolarization into the ventricles is thereby represented by the QRS wave. The plateau phase of the cardiac action potential is related to the S-T segment of the ECG. Finally, repolarization of the ventricles produces the T wave. You might be surprised that ventricular depolarization (the QRS wave) and repolarization (the T wave) point in the same direction, although they are produced by opposite potential changes. This is because depolarization of the ventricles occurs from endocardium to epicardium, whereas repolarization spreads in the opposite direction, from epicardium to endocardium. There are two types of ECG recording electrodes, or “leads.” The bipolar limb leads record the voltage between electrodes placed on the wrists and legs. These bipolar leads include lead I (right arm to left arm), lead II (right arm to left leg), and lead III (left arm to left leg). The right leg is used as a ground lead. In the unipolar leads, voltage is recorded between a single “exploratory electrode” placed on the body and an electrode that is built into the electrocardiograph and maintained at zero potential (ground). The unipolar limb leads are placed on the right arm, left arm, and left leg, and are abbreviated AVR, AVL, and AVF, respectively.



The two coronary arteries that supply the myocardium arise from the sinuses behind two of the cusps of the aortic valve at the root of the aorta. Eddy currents keep the valves away from the orifices of the arteries, and they are patent throughout the cardiac cycle. Most of the venous blood returns to the heart through the coronary sinus and anterior cardiac veins, which drain into the right atrium. In addition, there are other vessels that empty directly into the heart chambers. These include arteriosinu­soidal vessels, sinusoidal capillary-like vessels that connect arterioles to the chambers; thebesian veins that connect capil­laries to the chambers; and a few arterioluminal vessels that are small arteries draining directly into the chambers. A few anastomoses occur between the coronary arterioles and extra­cardiac arterioles, especially around the mouths of the great veins. Anastomoses between coronary arterioles in humans only pass particles less than 40 μm in diameter, but evidence indicates that these channels enlarge and increase in number in patients with coronary artery disease.