Cardiovascular System Ch 18 and 19 Week 2

T lymphocytes

(also, T cells) lymphocytes that provide cellular-level immunity by physically attacking foreign or diseased cells

Cardiac Conduction

(1) The sinoatrial (SA) node and the remainder of the conduction system are at rest. (2) The SA node initiates the action potential, which sweeps across the atria. (3) After reaching the atrioventricular node, there is a delay of approximately 100 ms that allows the atria to complete pumping blood before the impulse is transmitted to the atrioventricular bundle. (4) Following the delay, the impulse travels through the atrioventricular bundle and bundle branches to the Purkinje fibers, and also reaches the right papillary muscle via the moderator band. (5) The impulse spreads to the contractile fibers of the ventricle. (6) Ventricular contraction begins.

Blood Flow from the Left Ventricle into the Great Vessels

(a) A transverse section through the heart illustrates the four heart valves during ventricular contraction. The two atrioventricular valves are closed, but the two semilunar valves are open. The atria and vessels have been removed. (b) A frontal view shows the closed mitral (bicuspid) valve that prevents backflow of blood into the left atrium. The aortic semilunar valve is open to allow blood to be ejected into the aorta.

Blood Flow from the Left Atrium to the Left Ventricle

(a) A transverse section through the heart illustrates the four heart valves. The two atrioventricular valves are open; the two semilunar valves are closed. The atria and vessels have been removed. (b) A frontal section through the heart illustrates blood flow through the mitral valve. When the mitral valve is open, it allows blood to move from the left atrium to the left ventricle. The aortic semilunar valve is closed to prevent backflow of blood from the aorta to the left ventricle.Figurea shows the atrioventricular valves closed while the two semilunar valves are open. This occurs when the ventricles contract to eject blood into the pulmonary trunk and aorta. Closure of the two atrioventricular valves prevents blood from being forced back into the atria. This stage can be seen from a frontal view in Figureb.

Cardiac Muscle

(a) Cardiac muscle cells have myofibrils composed of myofilaments arranged in sarcomeres, T tubules to transmit the impulse from the sarcolemma to the interior of the cell, numerous mitochondria for energy, and intercalated discs that are found at the junction of different cardiac muscle cells. (b) A photomicrograph of cardiac muscle cells shows the nuclei and intercalated discs. (c) An intercalated disc connects cardiac muscle cells and consists of desmosomes and gap junctions. LM × 1600. (Micrograph provided by the Regents of the University of Michigan Medical School © 2012)

Common ECG Abnormalities

(a) In a second-degree or partial block, one-half of the P waves are not followed by the QRS complex and T waves while the other half are. (b) In atrial fibrillation, the electrical pattern is abnormal prior to the QRS complex, and the frequency between the QRS complexes has increased. (c) In ventricular tachycardia, the shape of the QRS complex is abnormal. (d) In ventricular fibrillation, there is no normal electrical activity. (e) In a third-degree block, there is no correlation between atrial activity (the P wave) and ventricular activity (the QRS complex).

Action Potential in Cardiac Contractile Cells

(a) Note the long plateau phase due to the influx of calcium ions. The extended refractory period allows the cell to fully contract before another electrical event can occur. (b) The action potential for heart muscle is compared to that of skeletal muscle.

B lymphocytes

(also, B cells) lymphocytes that defend the body against specific pathogens and thereby provide specific immunity

immunoglobulins

(also, antibodies or gamma globulins) antigen-specific proteins produced by specialized B lymphocytes that protect the body by binding to foreign objects such as bacteria and viruses

aortic valve

(also, aortic semilunar valve) valve located at the base of the aorta

bundle of His

(also, atrioventricular bundle) group of specialized myocardial conductile cells that transmit the impulse from the AV node through the interventricular septum; form the left and right atrioventricular bundle branches

atrioventricular bundle

(also, bundle of His) group of specialized myocardial conductile cells that transmit the impulse from the AV node through the interventricular septum; form the left and right atrioventricular bundle branches

atrial reflex

(also, called Bainbridge reflex) autonomic reflex that responds to stretch receptors in the atria that send impulses to the cardioaccelerator area to increase HR when venous flow into the atria increases

Bainbridge reflex

(also, called atrial reflex) autonomic reflex that responds to stretch receptors in the atria that send impulses to the cardioaccelerator area to increase HR when venous flow into the atria increases

emigration

(also, diapedesis) process by which leukocytes squeeze through adjacent cells in a blood vessel wall to enter tissues

diapedesis

(also, emigration) process by which leukocytes squeeze through adjacent cells in a blood vessel wall to enter tissues

preload

(also, end diastolic volume) amount of blood in the ventricles at the end of atrial systole just prior to ventricular contraction

hemolytic disease of the newborn (HDN)

(also, erythroblastosis fetalis) disorder causing agglutination and hemolysis in an Rh+ fetus or newborn of an Rh− mother

red blood cells (RBCs)

(also, erythrocytes) one of the formed elements of blood that transports oxygen

packed cell volume (PCV)

(also, hematocrit) volume percentage of erythrocytes present in a sample of centrifuged blood

antibodies

(also, immunoglobulins or gamma globulins) antigen-specific proteins produced by specialized B lymphocytes that protect the body by binding to foreign objects such as bacteria and viruses

Bachmann's bundle

(also, interatrial band) group of specialized conducting cells that transmit the impulse directly from the SA node in the right atrium to the left atrium

isovolumic contraction

(also, isovolumetric contraction) initial phase of ventricular contraction in which tension and pressure in the ventricle increase, but no blood is pumped or ejected from the heart

anterior interventricular artery

(also, left anterior descending artery or LAD) major branch of the left coronary artery that follows the anterior interventricular sulcus

mitral valve

(also, left atrioventricular valve or bicuspid valve) valve located between the left atrium and ventricle; consists of two flaps of tissue

atrioventricular bundle branches

(also, left or right bundle branches) specialized myocardial conductile cells that arise from the bifurcation of the atrioventricular bundle and pass through the interventricular septum; lead to the Purkinje fibers and also to the right papillary muscle via the moderator band

white blood cells (WBCs)

(also, leukocytes) one of the formed elements of blood that provides defense against disease agents and foreign materials

left atrioventricular valve

(also, mitral valve or bicuspid valve) valve located between the left atrium and ventricle; consists of two flaps of tissue

bicuspid valve

(also, mitral valve or left atrioventricular valve) valve located between the left atrium and ventricle; consists of two flaps of tissue

hematocrit

(also, packed cell volume) volume percentage of erythrocytes in a sample of centrifuged blood

pericardium

(also, pericardial sac) membrane that separates the heart from other mediastinal structures; consists of two distinct, fused sublayers: the fibrous pericardium and the parietal pericardium

pericardial sac

(also, pericardium) membrane that separates the heart from other mediastinal structures; consists of two distinct, fused sublayers: the fibrous pericardium and the parietal pericardium

posterior interventricular artery

(also, posterior descending artery) branch of the right coronary artery that runs along the posterior portion of the interventricular sulcus toward the apex of the heart and gives rise to branches that supply the interventricular septum and portions of both ventricles

end diastolic volume (EDV)

(also, preload) the amount of blood in the ventricles at the end of atrial systole just prior to ventricular contraction

spontaneous depolarization

(also, prepotential depolarization) the mechanism that accounts for the autorhythmic property of cardiac muscle; the membrane potential increases as sodium ions diffuse through the always-open sodium ion channels and causes the electrical potential to rise

pulmonary valve

(also, pulmonary semilunar valve, the pulmonic valve, or the right semilunar valve) valve at the base of the pulmonary trunk that prevents backflow of blood into the right ventricle; consists of three flaps

erythrocyte

(also, red blood cell) mature myeloid blood cell that is composed mostly of hemoglobin and functions primarily in the transportation of oxygen and carbon dioxide

sickle cell disease

(also, sickle cell anemia) inherited blood disorder in which hemoglobin molecules are malformed, leading to the breakdown of RBCs that take on a characteristic sickle shape

cardiac skeleton

(also, skeleton of the heart) reinforced connective tissue located within the atrioventricular septum; includes four rings that surround the openings between the atria and ventricles, and the openings to the pulmonary trunk and aorta; the point of attachment for the heart valves

prepotential depolarization

(also, spontaneous depolarization) mechanism that accounts for the autorhythmic property of cardiac muscle; the membrane potential increases as sodium ions diffuse through the always-open sodium ion channels and causes the electrical potential to rise

platelets

(also, thrombocytes) one of the formed elements of blood that consists of cell fragments broken off from megakaryocytes

right atrioventricular valve

(also, tricuspid valve) valve located between the right atrium and ventricle; consists of three flaps of tissue

leukocyte

(also, white blood cell) colorless, nucleated blood cell, the chief function of which is to protect the body from disease

anastomosis

(plural = anastomoses) area where vessels unite to allow blood to circulate even if there may be partial blockage in another branch

atrium

(plural = atria) upper or receiving chamber of the heart that pumps blood into the lower chambers just prior to their contraction; the right atrium receives blood from the systemic circuit that flows into the right ventricle; the left atrium receives blood from the pulmonary circuit that flows into the left ventricle

septum

(plural = septa) walls or partitions that divide the heart into chambers

sulcus

(plural = sulci) fat-filled groove visible on the surface of the heart; coronary vessels are also located in these areas

hemopoietic stem cell

type of pluripotent stem cell that gives rise to the formed elements of blood (hemocytoblast)

Anemias caused by faulty or decreased RBC production include sickle cell anemia, iron deficiency anemia, vitamin deficiency anemia, and diseases of the bone marrow and stem cells.

A characteristic change in the shape of erythrocytes is seen in sickle cell disease (also referred to as sickle cell anemia). A genetic disorder, it is caused by production of an abnormal type of hemoglobin, called hemoglobin S, which delivers less oxygen to tissues and causes erythrocytes to assume a sickle (or crescent) shape, especially at low oxygen concentrations (Figure). These abnormally shaped cells can then become lodged in narrow capillaries because they are unable to fold in on themselves to squeeze through, blocking blood flow to tissues and causing a variety of serious problems from painful joints to delayed growth and even blindness and cerebrovascular accidents (strokes). Sickle cell anemia is a genetic condition particularly found in individuals of African descent.

In contrast to the ABO group antibodies, which are preformed, antibodies to the Rh antigen are produced only in Rh− individuals after exposure to the antigen. This process, called sensitization, occurs following a transfusion with Rh-incompatible blood or, more commonly, with the birth of an Rh+ baby to an Rh− mother. Problems are rare in a first pregnancy, since the baby's Rh+ cells rarely cross the placenta (the organ of gas and nutrient exchange between the baby and the mother). However, during or immediately after birth, the Rh− mother can be exposed to the baby's Rh+ cells (Figure). Research has shown that this occurs in about 13−14 percent of such pregnancies. After exposure, the mother's immune system begins to generate anti-Rh antibodies. If the mother should then conceive another Rh+ baby, the Rh antibodies she has produced can cross the placenta into the fetal bloodstream and destroy the fetal RBCs. This condition, known as hemolytic disease of the newborn (HDN) or erythroblastosis fetalis, may cause anemia in mild cases, but the agglutination and hemolysis can be so severe that without treatment the fetus may die in the womb or shortly after birth.

A drug known as RhoGAM, short for Rh immune globulin, can temporarily prevent the development of Rh antibodies in the Rh− mother, thereby averting this potentially serious disease for the fetus. RhoGAM antibodies destroy any fetal Rh+ erythrocytes that may cross the placental barrier. RhoGAM is normally administered to Rh− mothers during weeks 26−28 of pregnancy and within 72 hours following birth. It has proven remarkably effective in decreasing the incidence of HDN. Earlier we noted that the incidence of HDN in an Rh+ subsequent pregnancy to an Rh− mother is about 13-14 percent without preventive treatment. Since the introduction of RhoGAM in 1968, the incidence has dropped to about 0.1 percent in the United States.

One of the more common adverse effects of cancer chemotherapy is the destruction of leukocytes. Before his next scheduled chemotherapy treatment, a patient undergoes a blood test called an absolute neutrophil count (ANC), which reveals that his neutrophil count is 1900 cells per microliter. Would his healthcare team be likely to proceed with his chemotherapy treatment? Why?

A neutrophil count below 1800 cells per microliter is considered abnormal. Thus, this patient's ANC is at the low end of the normal range and there would be no reason to delay chemotherapy. In clinical practice, most patients are given chemotherapy if their ANC is above 1000.

Electrocardiogram

A normal tracing shows the P wave, QRS complex, and T wave. Also indicated are the PR, QT, QRS, and ST intervals, plus the P-R and S-T segments.

Heart Valve Structure and Function

A transverse section through the heart slightly above the level of the atrioventricular septum reveals all four heart valves along the same plane (Figure). The valves ensure unidirectional blood flow through the heart. Between the right atrium and the right ventricle is the right atrioventricular valve, or tricuspid valve. It typically consists of three flaps, or leaflets, made of endocardium reinforced with additional connective tissue. The flaps are connected by chordae tendineae to the papillary muscles, which control the opening and closing of the valves.

Major Factors Influencing Stroke Volume

Multiple factors impact preload, afterload, and contractility, and are the major considerations influencing SV.

Monocytes originate from myeloid stem cells. They normally represent 2-8 percent of the total leukocyte count. They are typically easily recognized by their large size of 12-20 µm and indented or horseshoe-shaped nuclei. Macrophages are monocytes that have left the circulation and phagocytize debris, foreign pathogens, worn-out erythrocytes, and many other dead, worn out, or damaged cells. Macrophages also release antimicrobial defensins and chemotactic chemicals that attract other leukocytes to the site of an infection. Some macrophages occupy fixed locations, whereas others wander through the tissue fluid.

Abnormally high counts of monocytes are associated with viral or fungal infections, tuberculosis, and some forms of leukemia and other chronic diseases. Abnormally low counts are typically caused by suppression of the bone marrow.

Plasma Proteins

About 7 percent of the volume of plasma—nearly all that is not water—is made of proteins. These include several plasma proteins (proteins that are unique to the plasma), plus a much smaller number of regulatory proteins, including enzymes and some hormones. The major components of plasma are summarized in Figure. The three major groups of plasma proteins are as follows: Albumin is the most abundant of the plasma proteins. Manufactured by the liver, albumin molecules serve as binding proteins—transport vehicles for fatty acids and steroid hormones. Recall that lipids are hydrophobic; however, their binding to albumin enables their transport in the watery plasma. Albumin is also the most significant contributor to the osmotic pressure of blood; that is, its presence holds water inside the blood vessels and draws water from the tissues, across blood vessel walls, and into the bloodstream. This in turn helps to maintain both blood volume and blood pressure. Albumin normally accounts for approximately 54 percent of the total plasma protein content, in clinical levels of 3.5-5.0 g/dL blood. The second most common plasma proteins are the globulins. A heterogeneous group, there are three main subgroups known as alpha, beta, and gamma globulins. The alpha and beta globulins transport iron, lipids, and the fat-soluble vitamins A, D, E, and K to the cells; like albumin, they also contribute to osmotic pressure. The gamma globulins are proteins involved in immunity and are better known as an antibodies or immunoglobulins. Although other plasma proteins are produced by the liver, immunoglobulins are produced by specialized leukocytes known as plasma cells. (Seek additional content for more information about immunoglobulins.) Globulins make up approximately 38 percent of the total plasma protein volume, in clinical levels of 1.0-1.5 g/dL blood. The least abundant plasma protein is fibrinogen. Like albumin and the alpha and beta globulins, fibrinogen is produced by the liver. It is essential for blood clotting, a process described later in this chapter. Fibrinogen accounts for about 7 percent of the total plasma protein volume, in clinical levels of 0.2-0.45 g/dL blood.

Membrane Potentials and Ion Movement in Cardiac Conductive Cells

Action potentials are considerably different between cardiac conductive cells and cardiac contractive cells. While Na+ and K+ play essential roles, Ca2+ is also critical for both types of cells. Unlike skeletal muscles and neurons, cardiac conductive cells do not have a stable resting potential. Conductive cells contain a series of sodium ion channels that allow a normal and slow influx of sodium ions that causes the membrane potential to rise slowly from an initial value of −60 mV up to about -40 mV. The resulting movement of sodium ions creates spontaneous depolarization (or prepotential depolarization). At this point, calcium ion channels open and Ca2+ enters the cell, further depolarizing it at a more rapid rate until it reaches a value of approximately +5 mV. At this point, the calcium ion channels close and K+ channels open, allowing outflux of K+ and resulting in repolarization. When the membrane potential reaches approximately −60 mV, the K+ channels close and Na+ channels open, and the prepotential phase begins again. This phenomenon explains the autorhythmicity properties of cardiac muscle (Figure).

Left Atrium

After exchange of gases in the pulmonary capillaries, blood returns to the left atrium high in oxygen via one of the four pulmonary veins. While the left atrium does not contain pectinate muscles, it does have an auricle that includes these pectinate ridges. Blood flows nearly continuously from the pulmonary veins back into the atrium, which acts as the receiving chamber, and from here through an opening into the left ventricle. Most blood flows passively into the heart while both the atria and ventricles are relaxed, but toward the end of the ventricular relaxation period, the left atrium will contract, pumping blood into the ventricle. This atrial contraction accounts for approximately 20 percent of ventricular filling. The opening between the left atrium and ventricle is guarded by the mitral valve.

Describe how the major pumping chambers, the ventricles, form within the developing heart.

After fusion of the two endocardial tubes into the single primitive heart, five regions quickly become visible. From the head, these are the truncus arteriosus, bulbus cordis, primitive ventricle, primitive atrium, and sinus venosus. Contractions propel the blood from the sinus venosus to the truncus arteriosus. About day 23, the heart begins to form an S-shaped structure within the pericardium. The bulbus cordis develops into the right ventricle, whereas the primitive ventricle becomes the left ventricle. The interventricular septum separating these begins to form about day 28. The atrioventricular valves form between weeks five to eight. At this point, the heart ventricles resemble the adult structure.

Afterload

Afterload refers to the tension that the ventricles must develop to pump blood effectively against the resistance in the vascular system. Any condition that increases resistance requires a greater afterload to force open the semilunar valves and pump the blood. Damage to the valves, such as stenosis, which makes them harder to open will also increase afterload. Any decrease in resistance decreases the afterload. Figure summarizes the major factors influencing SV, Figure summarizes the major factors influencing CO, and Table and Table summarize cardiac responses to increased and decreased blood flow and pressure in order to restore homeostasis.

Why is afterload important to cardiac function?

Afterload represents the resistance within the arteries to the flow of blood ejected from the ventricles. If uncompensated, if afterload increases, flow will decrease. In order for the heart to maintain adequate flow to overcome increasing afterload, it must pump more forcefully. This is one of the negative consequences of high blood pressure or hypertension.

Agranular Leukocytes

Agranular leukocytes contain smaller, less-visible granules in their cytoplasm than do granular leukocytes. The nucleus is simple in shape, sometimes with an indentation but without distinct lobes. There are two major types of agranulocytes: lymphocytes and monocytes (see [link]). Lymphocytes are the only formed element of blood that arises from lymphoid stem cells. Although they form initially in the bone marrow, much of their subsequent development and reproduction occurs in the lymphatic tissues. Lymphocytes are the second most common type of leukocyte, accounting for about 20-30 percent of all leukocytes, and are essential for the immune response. The size range of lymphocytes is quite extensive, with some authorities recognizing two size classes and others three. Typically, the large cells are 10-14 µm and have a smaller nucleus-to-cytoplasm ratio and more granules. The smaller cells are typically 6-9 µm with a larger volume of nucleus to cytoplasm, creating a "halo" effect. A few cells may fall outside these ranges, at 14-17 µm. This finding has led to the three size range classification.

Differentiation of Formed Elements from Stem Cells

All formed elements arise from stem cells of the red bone marrow. Recall that stem cells undergo mitosis plus cytokinesis (cellular division) to give rise to new daughter cells: One of these remains a stem cell and the other differentiates into one of any number of diverse cell types. Stem cells may be viewed as occupying a hierarchal system, with some loss of the ability to diversify at each step. The totipotent stem cell is the zygote, or fertilized egg. The totipotent (toti- = "all") stem cell gives rise to all cells of the human body. The next level is the pluripotent stem cell, which gives rise to multiple types of cells of the body and some of the supporting fetal membranes. Beneath this level, the mesenchymal cell is a stem cell that develops only into types of connective tissue, including fibrous connective tissue, bone, cartilage, and blood, but not epithelium, muscle, and nervous tissue. One step lower on the hierarchy of stem cells is the hemopoietic stem cell, or hemocytoblast. All of the formed elements of blood originate from this specific type of cell.

Characteristics of Leukocytes

Although leukocytes and erythrocytes both originate from hematopoietic stem cells in the bone marrow, they are very different from each other in many significant ways. For instance, leukocytes are far less numerous than erythrocytes: Typically there are only 5000 to 10,000 per µL. They are also larger than erythrocytes and are the only formed elements that are complete cells, possessing a nucleus and organelles. And although there is just one type of erythrocyte, there are many types of leukocytes. Most of these types have a much shorter lifespan than that of erythrocytes, some as short as a few hours or even a few minutes in the case of acute infection. One of the most distinctive characteristics of leukocytes is their movement. Whereas erythrocytes spend their days circulating within the blood vessels, leukocytes routinely leave the bloodstream to perform their defensive functions in the body's tissues. For leukocytes, the vascular network is simply a highway they travel and soon exit to reach their true destination. When they arrive, they are often given distinct names, such as macrophage or microglia, depending on their function. As shown in Figure, they leave the capillaries—the smallest blood vessels—or other small vessels through a process known as emigration (from the Latin for "removal") or diapedesis (dia- = "through"; -pedan = "to leap") in which they squeeze through adjacent cells in a blood vessel wall. Once they have exited the capillaries, some leukocytes will take up fixed positions in lymphatic tissue, bone marrow, the spleen, the thymus, or other organs. Others will move about through the tissue spaces very much like amoebas, continuously extending their plasma membranes, sometimes wandering freely, and sometimes moving toward the direction in which they are drawn by chemical signals. This attracting of leukocytes occurs because of positive chemotaxis (literally "movement in response to chemicals"), a phenomenon in which injured or infected cells and nearby leukocytes emit the equivalent of a chemical "911" call, attracting more leukocytes to the site. In clinical medicine, the differential counts of the types and percentages of leukocytes present are often key indicators in making a diagnosis and selecting a treatment.

The ABO Blood Group

Although the ABO blood group name consists of three letters, ABO blood typing designates the presence or absence of just two antigens, A and B. Both are glycoproteins. People whose erythrocytes have A antigens on their erythrocyte membrane surfaces are designated blood type A, and those whose erythrocytes have B antigens are blood type B. People can also have both A and B antigens on their erythrocytes, in which case they are blood type AB. People with neither A nor B antigens are designated blood type O. ABO blood types are genetically determined. Normally the body must be exposed to a foreign antigen before an antibody can be produced. This is not the case for the ABO blood group. Individuals with type A blood—without any prior exposure to incompatible blood—have preformed antibodies to the B antigen circulating in their blood plasma. These antibodies, referred to as anti-B antibodies, will cause agglutination and hemolysis if they ever encounter erythrocytes with B antigens. Similarly, an individual with type B blood has pre-formed anti-A antibodies. Individuals with type AB blood, which has both antigens, do not have preformed antibodies to either of these. People with type O blood lack antigens A and B on their erythrocytes, but both anti-A and anti-B antibodies circulate in their blood plasma.

Heart Musculature-The swirling pattern of cardiac muscle tissue contributes significantly to the heart's ability to pump blood effectively.

Although the ventricles on the right and left sides pump the same amount of blood per contraction, the muscle of the left ventricle is much thicker and better developed than that of the right ventricle. In order to overcome the high resistance required to pump blood into the long systemic circuit, the left ventricle must generate a great amount of pressure. The right ventricle does not need to generate as much pressure, since the pulmonary circuit is shorter and provides less resistance. Figure illustrates the differences in muscular thickness needed for each of the ventricles.

Plasma Anticoagulants

An anticoagulant is any substance that opposes coagulation. Several circulating plasma anticoagulants play a role in limiting the coagulation process to the region of injury and restoring a normal, clot-free condition of blood. For instance, a cluster of proteins collectively referred to as the protein C system inactivates clotting factors involved in the intrinsic pathway. TFPI (tissue factor pathway inhibitor) inhibits the conversion of the inactive factor VII to the active form in the extrinsic pathway. Antithrombin inactivates factor X and opposes the conversion of prothrombin (factor II) to thrombin in the common pathway. And as noted earlier, basophils release heparin, a short-acting anticoagulant that also opposes prothrombin. Heparin is also found on the surfaces of cells lining the blood vessels. A pharmaceutical form of heparin is often administered therapeutically, for example, in surgical patients at risk for blood clots.

Which of the following describes a neutrophil?

abundant, granular, especially effective against bacteria

Assorted disease processes can also interfere with the production and formation of RBCs and hemoglobin. If myeloid stem cells are defective or replaced by cancer cells, there will be insufficient quantities of RBCs produced.

Aplastic anemia is the condition in which there are deficient numbers of RBC stem cells. Aplastic anemia is often inherited, or it may be triggered by radiation, medication, chemotherapy, or infection. Thalassemia is an inherited condition typically occurring in individuals from the Middle East, the Mediterranean, African, and Southeast Asia, in which maturation of the RBCs does not proceed normally. The most severe form is called Cooley's anemia. Lead exposure from industrial sources or even dust from paint chips of iron-containing paints or pottery that has not been properly glazed may also lead to destruction of the red marrow.

Antigens, Antibodies, and Transfusion Reactions

Antigens are substances that the body does not recognize as belonging to the "self" and that therefore trigger a defensive response from the leukocytes of the immune system. (Seek more content for additional information on immunity.) Here, we will focus on the role of immunity in blood transfusion reactions. With RBCs in particular, you may see the antigens referred to as isoantigens or agglutinogens (surface antigens) and the antibodies referred to as isoantibodies or agglutinins. In this chapter, we will use the more common terms antigens and antibodies. Antigens are generally large proteins, but may include other classes of organic molecules, including carbohydrates, lipids, and nucleic acids. Following an infusion of incompatible blood, erythrocytes with foreign antigens appear in the bloodstream and trigger an immune response. Proteins called antibodies (immunoglobulins), which are produced by certain B lymphocytes called plasma cells, attach to the antigens on the plasma membranes of the infused erythrocytes and cause them to adhere to one another. Because the arms of the Y-shaped antibodies attach randomly to more than one nonself erythrocyte surface, they form clumps of erythrocytes. This process is called agglutination. The clumps of erythrocytes block small blood vessels throughout the body, depriving tissues of oxygen and nutrients. As the erythrocyte clumps are degraded, in a process called hemolysis, their hemoglobin is released into the bloodstream. This hemoglobin travels to the kidneys, which are responsible for filtration of the blood. However, the load of hemoglobin released can easily overwhelm the kidney's capacity to clear it, and the patient can quickly develop kidney failure. More than 50 antigens have been identified on erythrocyte membranes, but the most significant in terms of their potential harm to patients are classified in two groups: the ABO blood group and the Rh blood group.

A patient was admitted to the burn unit the previous evening suffering from a severe burn involving his left upper extremity and shoulder. A blood test reveals that he is experiencing leukocytosis. Why is this an expected finding?

Any severe stress can increase the leukocyte count, resulting in leukocytosis. A burn is especially likely to increase the proliferation of leukocytes in order to ward off infection, a significant risk when the barrier function of the skin is destroyed.

Atrioventricular Bundle (Bundle of His), Bundle Branches, and Purkinje Fibers

Arising from the AV node, the atrioventricular bundle, or bundle of His, proceeds through the interventricular septum before dividing into two atrioventricular bundle branches, commonly called the left and right bundle branches. The left bundle branch has two fascicles. The left bundle branch supplies the left ventricle, and the right bundle branch the right ventricle. Since the left ventricle is much larger than the right, the left bundle branch is also considerably larger than the right. Portions of the right bundle branch are found in the moderator band and supply the right papillary muscles. Because of this connection, each papillary muscle receives the impulse at approximately the same time, so they begin to contract simultaneously just prior to the remainder of the myocardial contractile cells of the ventricles. This is believed to allow tension to develop on the chordae tendineae prior to right ventricular contraction. There is no corresponding moderator band on the left. Both bundle branches descend and reach the apex of the heart where they connect with the Purkinje fibers (see Figure, step 4). This passage takes approximately 25 ms. The Purkinje fibers are additional myocardial conductive fibers that spread the impulse to the myocardial contractile cells in the ventricles. They extend throughout the myocardium from the apex of the heart toward the atrioventricular septum and the base of the heart. The Purkinje fibers have a fast inherent conduction rate, and the electrical impulse reaches all of the ventricular muscle cells in about 75 ms (see Figure, step 5). Since the electrical stimulus begins at the apex, the contraction also begins at the apex and travels toward the base of the heart, similar to squeezing a tube of toothpaste from the bottom. This allows the blood to be pumped out of the ventricles and into the aorta and pulmonary trunk. The total time elapsed from the initiation of the impulse in the SA node until depolarization of the ventricles is approximately 225 ms.

Phases of the Cardiac Cycle

At the beginning of the cardiac cycle, both the atria and ventricles are relaxed (diastole). Blood is flowing into the right atrium from the superior and inferior venae cavae and the coronary sinus. Blood flows into the left atrium from the four pulmonary veins. The two atrioventricular valves, the tricuspid and mitral valves, are both open, so blood flows unimpeded from the atria and into the ventricles. Approximately 70-80 percent of ventricular filling occurs by this method. The two semilunar valves, the pulmonary and aortic valves, are closed, preventing backflow of blood into the right and left ventricles from the pulmonary trunk on the right and the aorta on the left.

platelet plug

accumulation and adhesion of platelets at the site of blood vessel injury

Shape and Structure of Erythrocytes

As an erythrocyte matures in the red bone marrow, it extrudes its nucleus and most of its other organelles. During the first day or two that it is in the circulation, an immature erythrocyte, known as a reticulocyte, will still typically contain remnants of organelles. Reticulocytes should comprise approximately 1-2 percent of the erythrocyte count and provide a rough estimate of the rate of RBC production, with abnormally low or high rates indicating deviations in the production of these cells. These remnants, primarily of networks (reticulum) of ribosomes, are quickly shed, however, and mature, circulating erythrocytes have few internal cellular structural components. Lacking mitochondria, for example, they rely on anaerobic respiration. This means that they do not utilize any of the oxygen they are transporting, so they can deliver it all to the tissues. They also lack endoplasmic reticula and do not synthesize proteins. Erythrocytes do, however, contain some structural proteins that help the blood cells maintain their unique structure and enable them to change their shape to squeeze through capillaries. This includes the protein spectrin, a cytoskeletal protein element. Erythrocytes are biconcave disks; that is, they are plump at their periphery and very thin in the center (Figure). Since they lack most organelles, there is more interior space for the presence of the hemoglobin molecules that, as you will see shortly, transport gases. The biconcave shape also provides a greater surface area across which gas exchange can occur, relative to its volume; a sphere of a similar diameter would have a lower surface area-to-volume ratio. In the capillaries, the oxygen carried by the erythrocytes can diffuse into the plasma and then through the capillary walls to reach the cells, whereas some of the carbon dioxide produced by the cells as a waste product diffuses into the capillaries to be picked up by the erythrocytes. Capillary beds are extremely narrow, slowing the passage of the erythrocytes and providing an extended opportunity for gas exchange to occur. However, the space within capillaries can be so minute that, despite their own small size, erythrocytes may have to fold in on themselves if they are to make their way through. Fortunately, their structural proteins like spectrin are flexible, allowing them to bend over themselves to a surprising degree, then spring back again when they enter a wider vessel. In wider vessels, erythrocytes may stack up much like a roll of coins, forming a rouleaux, from the French word for "roll."

The five regions of the primitive heart tube develop into recognizable structures in a fully developed heart. The truncus arteriosus will eventually divide and give rise to the ascending aorta and pulmonary trunk. The bulbus cordis develops into the right ventricle. The primitive ventricle forms the left ventricle. The primitive atrium becomes the anterior portions of both the right and left atria, and the two auricles. The sinus venosus develops into the posterior portion of the right atrium, the SA node, and the coronary sinus.

As the primitive heart tube elongates, it begins to fold within the pericardium, eventually forming an S shape, which places the chambers and major vessels into an alignment similar to the adult heart. This process occurs between days 23 and 28. The remainder of the heart development pattern includes development of septa and valves, and remodeling of the actual chambers. Partitioning of the atria and ventricles by the interatrial septum, interventricular septum, and atrioventricular septum is complete by the end of the fifth week, although the fetal blood shunts remain until birth or shortly after. The atrioventricular valves form between weeks five and eight, and the semilunar valves form between weeks five and nine.

Emerging from the right ventricle at the base of the pulmonary trunk is the pulmonary semilunar valve, or the pulmonary valve; it is also known as the pulmonic valve or the right semilunar valve. The pulmonary valve is comprised of three small flaps of endothelium reinforced with connective tissue. When the ventricle relaxes, the pressure differential causes blood to flow back into the ventricle from the pulmonary trunk. This flow of blood fills the pocket-like flaps of the pulmonary valve, causing the valve to close and producing an audible sound. Unlike the atrioventricular valves, there are no papillary muscles or chordae tendineae associated with the pulmonary valve. Located at the opening between the left atrium and left ventricle is the mitral valve, also called the bicuspid valve or the left atrioventricular valve. Structurally, this valve consists of two cusps, known as the anterior medial cusp and the posterior medial cusp, compared to the three cusps of the tricuspid valve. In a clinical setting, the valve is referred to as the mitral valve, rather than the bicuspid valve. The two cusps of the mitral valve are attached by chordae tendineae to two papillary muscles that project from the wall of the ventricle.

At the base of the aorta is the aortic semilunar valve, or the aortic valve, which prevents backflow from the aorta. It normally is composed of three flaps. When the ventricle relaxes and blood attempts to flow back into the ventricle from the aorta, blood will fill the cusps of the valve, causing it to close and producing an audible sound. In Figurea, the two atrioventricular valves are open and the two semilunar valves are closed. This occurs when both atria and ventricles are relaxed and when the atria contract to pump blood into the ventricles. Figureb shows a frontal view. Although only the left side of the heart is illustrated, the process is virtually identical on the right.

The three major groups of lymphocytes include natural killer cells, B cells, and T cells. Natural killer (NK) cells are capable of recognizing cells that do not express "self" proteins on their plasma membrane or that contain foreign or abnormal markers. These "nonself" cells include cancer cells, cells infected with a virus, and other cells with atypical surface proteins. Thus, they provide generalized, nonspecific immunity. The larger lymphocytes are typically NK cells.

B cells and T cells, also called B lymphocytes and T lymphocytes, play prominent roles in defending the body against specific pathogens (disease-causing microorganisms) and are involved in specific immunity. One form of B cells (plasma cells) produces the antibodies or immunoglobulins that bind to specific foreign or abnormal components of plasma membranes. This is also referred to as humoral (body fluid) immunity. T cells provide cellular-level immunity by physically attacking foreign or diseased cells. A memory cell is a variety of both B and T cells that forms after exposure to a pathogen and mounts rapid responses upon subsequent exposures. Unlike other leukocytes, memory cells live for many years. B cells undergo a maturation process in the bone marrow, whereas T cells undergo maturation in the thymus. This site of the maturation process gives rise to the name B and T cells. The functions of lymphocytes are complex and will be covered in detail in the chapter covering the lymphatic system and immunity. Smaller lymphocytes are either B or T cells, although they cannot be differentiated in a normal blood smear. Abnormally high lymphocyte counts are characteristic of viral infections as well as some types of cancer. Abnormally low lymphocyte counts are characteristic of prolonged (chronic) illness or immunosuppression, including that caused by HIV infection and drug therapies that often involve steroids.

Cardiac Response to Decreasing Blood Flow and Pressure Due to Decreasing Cardiac Output

Baroreceptors (aorta, carotid arteries, venae cavae, and atria) Chemoreceptors (both central nervous system and in proximity to baroreceptors) Sensitive to Decreasing stretch Decreasing O2 and increasing CO2, H+, and lactic acid Target Parasympathetic stimulation suppressed Sympathetic stimulation increased Response of heart Increasing heart rate and increasing stroke volume Increasing heart rate and increasing stroke volume Overall effect Increasing blood flow and pressure due to increasing cardiac output; hemostasis restored Increasing blood flow and pressure due to increasing cardiac output; hemostasis restored

Cardiac Response to Increasing Blood Flow and Pressure Due to Increasing Cardiac Output

Baroreceptors (aorta, carotid arteries, venae cavae, and atria) Chemoreceptors (both central nervous system and in proximity to baroreceptors) Sensitive to Increasing stretch Increasing O2 and decreasing CO2, H+, and lactic acid Target Parasympathetic stimulation increased Sympathetic stimulation suppressed Response of heart Decreasing heart rate and decreasing stroke volume Decreasing heart rate and decreasing stroke volume Overall effect Decreasing blood flow and pressure due to decreasing cardiac output; hemostasis restored Decreasing blood flow and pressure due to decreasing cardiac output; hemostasis restored

A patient has thalassemia, a genetic disorder characterized by abnormal synthesis of globin proteins and excessive destruction of erythrocytes. This patient is jaundiced and is found to have an excessive level of bilirubin in his blood. Explain the connection.

Bilirubin is a breakdown product of the non-iron component of heme, which is cleaved from globin when erythrocytes are degraded. Excessive erythrocyte destruction would deposit excessive bilirubin in the blood. Bilirubin is a yellowish pigment, and high blood levels can manifest as yellowed skin.

dual system of the human blood circulation

Blood flows from the right atrium to the right ventricle, where it is pumped into the pulmonary circuit. The blood in the pulmonary artery branches is low in oxygen but relatively high in carbon dioxide. Gas exchange occurs in the pulmonary capillaries (oxygen into the blood, carbon dioxide out), and blood high in oxygen and low in carbon dioxide is returned to the left atrium. From here, blood enters the left ventricle, which pumps it into the systemic circuit. Following exchange in the systemic capillaries (oxygen and nutrients out of the capillaries and carbon dioxide and wastes in), blood returns to the right atrium and the cycle is repeated.

Which of the following statements about blood is true?

Blood is slightly more viscous than water.

Common Pathway

Both the intrinsic and extrinsic pathways lead to the common pathway, in which fibrin is produced to seal off the vessel. Once factor X has been activated by either the intrinsic or extrinsic pathway, the enzyme prothrombinase converts factor II, the inactive enzyme prothrombin, into the active enzyme thrombin. (Note that if the enzyme thrombin were not normally in an inactive form, clots would form spontaneously, a condition not consistent with life.) Then, thrombin converts factor I, the soluble fibrinogen, into the insoluble fibrin protein strands. Factor XIII then stabilizes the fibrin clot.

Electrocardiogram

By careful placement of surface electrodes on the body, it is possible to record the complex, compound electrical signal of the heart. This tracing of the electrical signal is the electrocardiogram (ECG), also commonly abbreviated EKG (K coming kardiology, from the German term for cardiology). Careful analysis of the ECG reveals a detailed picture of both normal and abnormal heart function, and is an indispensable clinical diagnostic tool. The standard electrocardiograph (the instrument that generates an ECG) uses 3, 5, or 12 leads. The greater the number of leads an electrocardiograph uses, the more information the ECG provides. The term "lead" may be used to refer to the cable from the electrode to the electrical recorder, but it typically describes the voltage difference between two of the electrodes. The 12-lead electrocardiograph uses 10 electrodes placed in standard locations on the patient's skin (Figure). In continuous ambulatory electrocardiographs, the patient wears a small, portable, battery-operated device known as a Holter monitor, or simply a Holter, that continuously monitors heart electrical activity, typically for a period of 24 hours during the patient's normal routine. A normal ECG tracing is presented in Figure. Each component, segment, and interval is labeled and corresponds to important electrical events, demonstrating the relationship between these events and contraction in the heart. There are five prominent points on the ECG: the P wave, the QRS complex, and the T wave. The small P wave represents the depolarization of the atria. The atria begin contracting approximately 25 ms after the start of the P wave. The large QRS complex represents the depolarization of the ventricles, which requires a much stronger electrical signal because of the larger size of the ventricular cardiac muscle. The ventricles begin to contract as the QRS reaches the peak of the R wave. Lastly, the T wave represents the repolarization of the ventricles. The repolarization of the atria occurs during the QRS complex, which masks it on an ECG. The major segments and intervals of an ECG tracing are indicated in Figure. Segments are defined as the regions between two waves. Intervals include one segment plus one or more waves. For example, the PR segment begins at the end of the P wave and ends at the beginning of the QRS complex. The PR interval starts at the beginning of the P wave and ends with the beginning of the QRS complex. The PR interval is more clinically relevant, as it measures the duration from the beginning of atrial depolarization (the P wave) to the initiation of the QRS complex. Since the Q wave may be difficult to view in some tracings, the measurement is often extended to the R that is more easily visible. Should there be a delay in passage of the impulse from the SA node to the AV node, it would be visible in the PR interval. Figure correlates events of heart contraction to the corresponding segments and intervals of an ECG.

Which of the following is a positive inotrope?

Ca2+

eosinophils

granulocytes that stain with eosin; they release antihistamines and are especially active against parasitic worms

Caffeine and Nicotine

Caffeine and nicotine are not found naturally within the body. Both of these nonregulated drugs have an excitatory effect on membranes of neurons in general and have a stimulatory effect on the cardiac centers specifically, causing an increase in HR. Caffeine works by increasing the rates of depolarization at the SA node, whereas nicotine stimulates the activity of the sympathetic neurons that deliver impulses to the heart. Although it is the world's most widely consumed psychoactive drug, caffeine is legal and not regulated. While precise quantities have not been established, "normal" consumption is not considered harmful to most people, although it may cause disruptions to sleep and acts as a diuretic. Its consumption by pregnant women is cautioned against, although no evidence of negative effects has been confirmed. Tolerance and even physical and mental addiction to the drug result in individuals who routinely consume the substance. Nicotine, too, is a stimulant and produces addiction. While legal and nonregulated, concerns about nicotine's safety and documented links to respiratory and cardiac disease have resulted in warning labels on cigarette packages.

Calcium

Calcium ion levels have great impacts upon both HR and contractility; as the levels of calcium ions increase, so do HR and contractility. High levels of calcium ions (hypercalcemia) may be implicated in a short QT interval and a widened T wave in the ECG. The QT interval represents the time from the start of depolarization to repolarization of the ventricles, and includes the period of ventricular systole. Extremely high levels of calcium may induce cardiac arrest. Drugs known as calcium channel blockers slow HR by binding to these channels and blocking or slowing the inward movement of calcium ions.

Calcium Ions

Calcium ions play two critical roles in the physiology of cardiac muscle. Their influx through slow calcium channels accounts for the prolonged plateau phase and absolute refractory period that enable cardiac muscle to function properly. Calcium ions also combine with the regulatory protein troponin in the troponin-tropomyosin complex; this complex removes the inhibition that prevents the heads of the myosin molecules from forming cross bridges with the active sites on actin that provide the power stroke of contraction. This mechanism is virtually identical to that of skeletal muscle. Approximately 20 percent of the calcium required for contraction is supplied by the influx of Ca2+ during the plateau phase. The remaining Ca2+ for contraction is released from storage in the sarcoplasmic reticulum.

`Resting Cardiac Output

Cardiac output (CO) is a measurement of the amount of blood pumped by each ventricle in one minute. To calculate this value, multiply stroke volume (SV), the amount of blood pumped by each ventricle, by heart rate (HR), in contractions per minute (or beats per minute, bpm). It can be represented mathematically by the following equation: CO = HR × SV SV is normally measured using an echocardiogram to record EDV and ESV, and calculating the difference: SV = EDV - ESV. SV can also be measured using a specialized catheter, but this is an invasive procedure and far more dangerous to the patient. A mean SV for a resting 70-kg (150-lb) individual would be approximately 70 mL. There are several important variables, including size of the heart, physical and mental condition of the individual, sex, contractility, duration of contraction, preload or EDV, and afterload or resistance. Normal range for SV would be 55-100 mL. An average resting HR would be approximately 75 bpm but could range from 60-100 in some individuals. Using these numbers, the mean CO is 5.25 L/min, with a range of 4.0-8.0 L/min. Remember, however, that these numbers refer to CO from each ventricle separately, not the total for the heart. Factors influencing CO are summarized in Figure. SVs are also used to calculate ejection fraction, which is the portion of the blood that is pumped or ejected from the heart with each contraction. To calculate ejection fraction, SV is divided by EDV. Despite the name, the ejection fraction is normally expressed as a percentage. Ejection fractions range from approximately 55-70 percent, with a mean of 58 percent.

Major Factors Influencing Cardiac Output

Cardiac output is influenced by heart rate and stroke volume, both of which are also variable.

Autonomic Innervation of the Heart

Cardioaccelerator and cardioinhibitory areas are components of the paired cardiac centers located in the medulla oblongata of the brain. They innervate the heart via sympathetic cardiac nerves that increase cardiac activity and vagus (parasympathetic) nerves that slow cardiac activity.

Cardiologist

Cardiologists are medical doctors that specialize in the diagnosis and treatment of diseases of the heart. After completing 4 years of medical school, cardiologists complete a three-year residency in internal medicine followed by an additional three or more years in cardiology. Following this 10-year period of medical training and clinical experience, they qualify for a rigorous two-day examination administered by the Board of Internal Medicine that tests their academic training and clinical abilities, including diagnostics and treatment. After successful completion of this examination, a physician becomes a board-certified cardiologist. Some board-certified cardiologists may be invited to become a Fellow of the American College of Cardiology (FACC). This professional recognition is awarded to outstanding physicians based upon merit, including outstanding credentials, achievements, and community contributions to cardiovascular medicine.

Cardiovascular Technologist/Technician

Cardiovascular technologists/technicians are trained professionals who perform a variety of imaging techniques, such as sonograms or echocardiograms, used by physicians to diagnose and treat diseases of the heart. Nearly all of these positions require an associate degree, and these technicians earn a median salary of $49,410 as of May 2010, according to the U.S. Bureau of Labor Statistics. Growth within the field is fast, projected at 29 percent from 2010 to 2020. There is a considerable overlap and complementary skills between cardiac technicians and vascular technicians, and so the term cardiovascular technician is often used. Special certifications within the field require documenting appropriate experience and completing additional and often expensive certification examinations. These subspecialties include Certified Rhythm Analysis Technician (CRAT), Certified Cardiographic Technician (CCT), Registered Congenital Cardiac Sonographer (RCCS), Registered Cardiac Electrophysiology Specialist (RCES), Registered Cardiovascular Invasive Specialist (RCIS), Registered Cardiac Sonographer (RCS), Registered Vascular Specialist (RVS), and Registered Phlebology Sonographer (RPhS).

Determining ABO Blood Types

Clinicians are able to determine a patient's blood type quickly and easily using commercially prepared antibodies. An unknown blood sample is allocated into separate wells. Into one well a small amount of anti-A antibody is added, and to another a small amount of anti-B antibody. If the antigen is present, the antibodies will cause visible agglutination of the cells (Figure). The blood should also be tested for Rh antibodies. Cross Matching Blood Types This figure shows three different red blood cells with different blood types. This sample of a commercially produced "bedside" card enables quick typing of both a recipient's and donor's blood before transfusion. The card contains three reaction sites or wells. One is coated with an anti-A antibody, one with an anti-B antibody, and one with an anti-D antibody (tests for the presence of Rh factor D). Mixing a drop of blood and saline into each well enables the blood to interact with a preparation of type-specific antibodies, also called anti-seras. Agglutination of RBCs in a given site indicates a positive identification of the blood antigens, in this case A and Rh antigens for blood type A+. For the purpose of transfusion, the donor's and recipient's blood types must match.

Factor number Name Type of molecule Source Pathway(s) I Fibrinogen Plasma protein Liver Common; converted into fibrin II Prothrombin Plasma protein Liver* Common; converted into thrombin III Tissue thromboplastin or tissue factor Lipoprotein mixture Damaged cells and platelets Extrinsic IV Calcium ions Inorganic ions in plasma Diet, platelets, bone matrix Entire process V Proaccelerin Plasma protein Liver, platelets Extrinsic and intrinsic VI Not used Not used Not used Not used VII Proconvertin Plasma protein Liver * Extrinsic VIII Antihemolytic factor A Plasma protein factor Platelets and endothelial cells Intrinsic; deficiency results in hemophilia A IX Antihemolytic factor B (plasma thromboplastin component) Plasma protein Liver* Intrinsic; deficiency results in hemophilia B X Stuart-Prower factor (thrombokinase) Protein Liver* Extrinsic and intrinsic XI Antihemolytic factor C (plasma thromboplastin antecedent) Plasma protein Liver Intrinsic; deficiency results in hemophilia C XII Hageman factor Plasma protein Liver Intrinsic; initiates clotting in vitro also activates plasmin XIII Fibrin-stabilizing factor Plasma protein Liver, platelets Stabilizes fibrin; slows fibrinolysis

Clotting Factors

to explore the intrinsic, extrinsic, and common pathways that are involved the process of coagulation. The coagulation cascade restores hemostasis by activating coagulation factors in the presence of an injury. How does the endothelium of the blood vessel walls prevent the blood from coagulating as it flows through the blood vessels?

Clotting factors flow through the blood vessels in their inactive state. The endothelium does not have thrombogenic tissue factor to activate clotting factors.

Structure of Cardiac Muscle

Compared to the giant cylinders of skeletal muscle, cardiac muscle cells, or cardiomyocytes, are considerably shorter with much smaller diameters. Cardiac muscle also demonstrates striations, the alternating pattern of dark A bands and light I bands attributed to the precise arrangement of the myofilaments and fibrils that are organized in sarcomeres along the length of the cell (Figurea). These contractile elements are virtually identical to skeletal muscle. T (transverse) tubules penetrate from the surface plasma membrane, the sarcolemma, to the interior of the cell, allowing the electrical impulse to reach the interior. The T tubules are only found at the Z discs, whereas in skeletal muscle, they are found at the junction of the A and I bands. Therefore, there are one-half as many T tubules in cardiac muscle as in skeletal muscle. In addition, the sarcoplasmic reticulum stores few calcium ions, so most of the calcium ions must come from outside the cells. The result is a slower onset of contraction. Mitochondria are plentiful, providing energy for the contractions of the heart. Typically, cardiomyocytes have a single, central nucleus, but two or more nuclei may be found in some cells. Cardiac muscle cells branch freely. A junction between two adjoining cells is marked by a critical structure called an intercalated disc, which helps support the synchronized contraction of the muscle (Figureb). The sarcolemmas from adjacent cells bind together at the intercalated discs. They consist of desmosomes, specialized linking proteoglycans, tight junctions, and large numbers of gap junctions that allow the passage of ions between the cells and help to synchronize the contraction (Figurec). Intercellular connective tissue also helps to bind the cells together. The importance of strongly binding these cells together is necessitated by the forces exerted by contraction. Cardiac muscle undergoes aerobic respiration patterns, primarily metabolizing lipids and carbohydrates. Myoglobin, lipids, and glycogen are all stored within the cytoplasm. Cardiac muscle cells undergo twitch-type contractions with long refractory periods followed by brief relaxation periods. The relaxation is essential so the heart can fill with blood for the next cycle. The refractory period is very long to prevent the possibility of tetany, a condition in which muscle remains involuntarily contracted. In the heart, tetany is not compatible with life, since it would prevent the heart from pumping blood.

Coronary Arteries

Coronary arteries supply blood to the myocardium and other components of the heart. The first portion of the aorta after it arises from the left ventricle gives rise to the coronary arteries. There are three dilations in the wall of the aorta just superior to the aortic semilunar valve. Two of these, the left posterior aortic sinus and anterior aortic sinus, give rise to the left and right coronary arteries, respectively. The third sinus, the right posterior aortic sinus, typically does not give rise to a vessel. Coronary vessel branches that remain on the surface of the artery and follow the sulci are called epicardial coronary arteries. The left coronary artery distributes blood to the left side of the heart, the left atrium and ventricle, and the interventricular septum. The circumflex artery arises from the left coronary artery and follows the coronary sulcus to the left. Eventually, it will fuse with the small branches of the right coronary artery. The larger anterior interventricular artery, also known as the left anterior descending artery (LAD), is the second major branch arising from the left coronary artery. It follows the anterior interventricular sulcus around the pulmonary trunk. Along the way it gives rise to numerous smaller branches that interconnect with the branches of the posterior interventricular artery, forming anastomoses. An anastomosis is an area where vessels unite to form interconnections that normally allow blood to circulate to a region even if there may be partial blockage in another branch. The anastomoses in the heart are very small. Therefore, this ability is somewhat restricted in the heart so a coronary artery blockage often results in death of the cells (myocardial infarction) supplied by the particular vessel. The right coronary artery proceeds along the coronary sulcus and distributes blood to the right atrium, portions of both ventricles, and the heart conduction system. Normally, one or more marginal arteries arise from the right coronary artery inferior to the right atrium. The marginal arteries supply blood to the superficial portions of the right ventricle. On the posterior surface of the heart, the right coronary artery gives rise to the posterior interventricular artery, also known as the posterior descending artery. It runs along the posterior portion of the interventricular sulcus toward the apex of the heart, giving rise to branches that supply the interventricular septum and portions of both ventricles. Figure presents views of the coronary circulation from both the anterior and posterior views.

Atrial Systole and Diastole

Contraction of the atria follows depolarization, represented by the P wave of the ECG. As the atrial muscles contract from the superior portion of the atria toward the atrioventricular septum, pressure rises within the atria and blood is pumped into the ventricles through the open atrioventricular (tricuspid, and mitral or bicuspid) valves. At the start of atrial systole, the ventricles are normally filled with approximately 70-80 percent of their capacity due to inflow during diastole. Atrial contraction, also referred to as the "atrial kick," contributes the remaining 20-30 percent of filling (see Figure). Atrial systole lasts approximately 100 ms and ends prior to ventricular systole, as the atrial muscle returns to diastole.

Heart: Coronary Artery Disease

Coronary artery disease is the leading cause of death worldwide. It occurs when the buildup of plaque—a fatty material including cholesterol, connective tissue, white blood cells, and some smooth muscle cells—within the walls of the arteries obstructs the flow of blood and decreases the flexibility or compliance of the vessels. This condition is called atherosclerosis, a hardening of the arteries that involves the accumulation of plaque. As the coronary blood vessels become occluded, the flow of blood to the tissues will be restricted, a condition called ischemia that causes the cells to receive insufficient amounts of oxygen, called hypoxia. Figure shows the blockage of coronary arteries highlighted by the injection of dye. Some individuals with coronary artery disease report pain radiating from the chest called angina pectoris, but others remain asymptomatic. If untreated, coronary artery disease can lead to MI or a heart attackThe disease progresses slowly and often begins in children and can be seen as fatty "streaks" in the vessels. It then gradually progresses throughout life. Well-documented risk factors include smoking, family history, hypertension, obesity, diabetes, high alcohol consumption, lack of exercise, stress, and hyperlipidemia or high circulating levels of lipids in the blood. Treatments may include medication, changes to diet and exercise, angioplasty with a balloon catheter, insertion of a stent, or coronary bypass procedure. Angioplasty is a procedure in which the occlusion is mechanically widened with a balloon. A specialized catheter with an expandable tip is inserted into a superficial vessel, normally in the leg, and then directed to the site of the occlusion. At this point, the balloon is inflated to compress the plaque material and to open the vessel to increase blood flow. Then, the balloon is deflated and retracted. A stent consisting of a specialized mesh is typically inserted at the site of occlusion to reinforce the weakened and damaged walls. Stent insertions have been routine in cardiology for more than 40 years. Coronary bypass surgery may also be performed. This surgical procedure grafts a replacement vessel obtained from another, less vital portion of the body to bypass the occluded area. This procedure is clearly effective in treating patients experiencing a MI, but overall does not increase longevity. Nor does it seem advisable in patients with stable although diminished cardiac capacity since frequently loss of mental acuity occurs following the procedure. Long-term changes to behavior, emphasizing diet and exercise plus a medicine regime tailored to lower blood pressure, lower cholesterol and lipids, and reduce clotting are equally as effective.

Coronary Veins

Coronary veins drain the heart and generally parallel the large surface arteries (see Figure). The great cardiac vein can be seen initially on the surface of the heart following the interventricular sulcus, but it eventually flows along the coronary sulcus into the coronary sinus on the posterior surface. The great cardiac vein initially parallels the anterior interventricular artery and drains the areas supplied by this vessel. It receives several major branches, including the posterior cardiac vein, the middle cardiac vein, and the small cardiac vein. The posterior cardiac vein parallels and drains the areas supplied by the marginal artery branch of the circumflex artery. The middle cardiac vein parallels and drains the areas supplied by the posterior interventricular artery. The small cardiac vein parallels the right coronary artery and drains the blood from the posterior surfaces of the right atrium and ventricle. The coronary sinus is a large, thin-walled vein on the posterior surface of the heart lying within the atrioventricular sulcus and emptying directly into the right atrium. The anterior cardiac veins parallel the small cardiac arteries and drain the anterior surface of the right ventricle. Unlike these other cardiac veins, it bypasses the coronary sinus and drains directly into the right atrium.

Repair and Replacement

Damaged cardiac muscle cells have extremely limited abilities to repair themselves or to replace dead cells via mitosis. Recent evidence indicates that at least some stem cells remain within the heart that continue to divide and at least potentially replace these dead cells. However, newly formed or repaired cells are rarely as functional as the original cells, and cardiac function is reduced. In the event of a heart attack or MI, dead cells are often replaced by patches of scar tissue. Autopsies performed on individuals who had successfully received heart transplants show some proliferation of original cells. If researchers can unlock the mechanism that generates new cells and restore full mitotic capabilities to heart muscle, the prognosis for heart attack survivors will be greatly enhanced. To date, myocardial cells produced within the patient (in situ) by cardiac stem cells seem to be nonfunctional, although those grown in Petri dishes (in vitro) do beat. Perhaps soon this mystery will be solved, and new advances in treatment will be commonplace.

Hemopoietic Growth Factors

Development from stem cells to precursor cells to mature cells is again initiated by hemopoietic growth factors. These include the following: Erythropoietin (EPO) is a glycoprotein hormone secreted by the interstitial fibroblast cells of the kidneys in response to low oxygen levels. It prompts the production of erythrocytes. Some athletes use synthetic EPO as a performance-enhancing drug (called blood doping) to increase RBC counts and subsequently increase oxygen delivery to tissues throughout the body. EPO is a banned substance in most organized sports, but it is also used medically in the treatment of certain anemia, specifically those triggered by certain types of cancer, and other disorders in which increased erythrocyte counts and oxygen levels are desirable. Thrombopoietin, another glycoprotein hormone, is produced by the liver and kidneys. It triggers the development of megakaryocytes into platelets. Cytokines are glycoproteins secreted by a wide variety of cells, including red bone marrow, leukocytes, macrophages, fibroblasts, and endothelial cells. They act locally as autocrine or paracrine factors, stimulating the proliferation of progenitor cells and helping to stimulate both nonspecific and specific resistance to disease. There are two major subtypes of cytokines known as colony-stimulating factors and interleukins. Colony-stimulating factors (CSFs) are glycoproteins that act locally, as autocrine or paracrine factors. Some trigger the differentiation of myeloblasts into granular leukocytes, namely, neutrophils, eosinophils, and basophils. These are referred to as granulocyte CSFs. A different CSF induces the production of monocytes, called monocyte CSFs. Both granulocytes and monocytes are stimulated by GM-CSF; granulocytes, monocytes, platelets, and erythrocytes are stimulated by multi-CSF. Synthetic forms of these hormones are often administered to patients with various forms of cancer who are receiving chemotherapy to revive their WBC counts. Interleukins are another class of cytokine signaling molecules important in hemopoiesis. They were initially thought to be secreted uniquely by leukocytes and to communicate only with other leukocytes, and were named accordingly, but are now known to be produced by a variety of cells including bone marrow and endothelium. Researchers now suspect that interleukins may play other roles in body functioning, including differentiation and maturation of cells, producing immunity and inflammation. To date, more than a dozen interleukins have been identified, with others likely to follow. They are generally numbered IL-1, IL-2, IL-3, etc.

biliverdin

green bile pigment produced when the non-iron portion of heme is degraded into a waste product; converted to bilirubin in the liver

The term murmur is used to describe an unusual sound coming from the heart that is caused by the turbulent flow of blood. Murmurs are graded on a scale of 1 to 6, with 1 being the most common, the most difficult sound to detect, and the least serious. The most severe is a 6. Phonocardiograms or auscultograms can be used to record both normal and abnormal sounds using specialized electronic stethoscopes.

During auscultation, it is common practice for the clinician to ask the patient to breathe deeply. This procedure not only allows for listening to airflow, but it may also amplify heart murmurs. Inhalation increases blood flow into the right side of the heart and may increase the amplitude of right-sided heart murmurs. Expiration partially restricts blood flow into the left side of the heart and may amplify left-sided heart murmurs. Figure indicates proper placement of the bell of the stethoscope to facilitate auscultation.

ECG Abnormalities

ECG Abnormalities Occassionally, an area of the heart other than the SA node will initiate an impulse that will be followed by a premature contraction. Such an area, which may actually be a component of the conduction system or some other contractile cells, is known as an ectopic focus or ectopic pacemaker. An ectopic focus may be stimulated by localized ischemia; exposure to certain drugs, including caffeine, digitalis, or acetylcholine; elevated stimulation by both sympathetic or parasympathetic divisions of the autonomic nervous system; or a number of disease or pathological conditions. Occasional occurances are generally transitory and nonlife threatening, but if the condition becomes chronic, it may lead to either an arrhythmia, a deviation from the normal pattern of impulse conduction and contraction, or to fibrillation, an uncoordinated beating of the heart. While interpretation of an ECG is possible and extremely valuable after some training, a full understanding of the complexities and intricacies generally requires several years of experience. In general, the size of the electrical variations, the duration of the events, and detailed vector analysis provide the most comprehensive picture of cardiac function. For example, an amplified P wave may indicate enlargement of the atria, an enlarged Q wave may indicate a MI, and an enlarged suppressed or inverted Q wave often indicates enlarged ventricles. T waves often appear flatter when insufficient oxygen is being delivered to the myocardium. An elevation of the ST segment above baseline is often seen in patients with an acute MI, and may appear depressed below the baseline when hypoxia is occurring. As useful as analyzing these electrical recordings may be, there are limitations. For example, not all areas suffering a MI may be obvious on the ECG. Additionally, it will not reveal the effectiveness of the pumping, which requires further testing, such as an ultrasound test called an echocardiogram or nuclear medicine imaging. It is also possible for there to be pulseless electrical activity, which will show up on an ECG tracing, although there is no corresponding pumping action. Common abnormalities that may be detected by the ECGs are shown in Figure.

Disorders of Clotting

Either an insufficient or an excessive production of platelets can lead to severe disease or death. As discussed earlier, an insufficient number of platelets, called thrombocytopenia, typically results in the inability of blood to form clots. This can lead to excessive bleeding, even from minor wounds. Another reason for failure of the blood to clot is the inadequate production of functional amounts of one or more clotting factors. This is the case in the genetic disorder hemophilia, which is actually a group of related disorders, the most common of which is hemophilia A, accounting for approximately 80 percent of cases. This disorder results in the inability to synthesize sufficient quantities of factor VIII. Hemophilia B is the second most common form, accounting for approximately 20 percent of cases. In this case, there is a deficiency of factor IX. Both of these defects are linked to the X chromosome and are typically passed from a healthy (carrier) mother to her male offspring, since males are XY. Females would need to inherit a defective gene from each parent to manifest the disease, since they are XX. Patients with hemophilia bleed from even minor internal and external wounds, and leak blood into joint spaces after exercise and into urine and stool. Hemophilia C is a rare condition that is triggered by an autosomal (not sex) chromosome that renders factor XI nonfunctional. It is not a true recessive condition, since even individuals with a single copy of the mutant gene show a tendency to bleed. Regular infusions of clotting factors isolated from healthy donors can help prevent bleeding in hemophiliac patients. At some point, genetic therapy will become a viable option. In contrast to the disorders characterized by coagulation failure is thrombocytosis, also mentioned earlier, a condition characterized by excessive numbers of platelets that increases the risk for excessive clot formation, a condition known as thrombosis. A thrombus (plural = thrombi) is an aggregation of platelets, erythrocytes, and even WBCs typically trapped within a mass of fibrin strands. While the formation of a clot is normal following the hemostatic mechanism just described, thrombi can form within an intact or only slightly damaged blood vessel. In a large vessel, a thrombus will adhere to the vessel wall and decrease the flow of blood, and is referred to as a mural thrombus. In a small vessel, it may actually totally block the flow of blood and is termed an occlusive thrombus. Thrombi are most commonly caused by vessel damage to the endothelial lining, which activates the clotting mechanism. These may include venous stasis, when blood in the veins, particularly in the legs, remains stationary for long periods. This is one of the dangers of long airplane flights in crowded conditions and may lead to deep vein thrombosis or atherosclerosis, an accumulation of debris in arteries. Thrombophilia, also called hypercoagulation, is a condition in which there is a tendency to form thrombosis. This may be familial (genetic) or acquired. Acquired forms include the autoimmune disease lupus, immune reactions to heparin, polycythemia vera, thrombocytosis, sickle cell disease, pregnancy, and even obesity. A thrombus can seriously impede blood flow to or from a region and will cause a local increase in blood pressure. If flow is to be maintained, the heart will need to generate a greater pressure to overcome the resistance. When a portion of a thrombus breaks free from the vessel wall and enters the circulation, it is referred to as an embolus. An embolus that is carried through the bloodstream can be large enough to block a vessel critical to a major organ. When it becomes trapped, an embolus is called an embolism. In the heart, brain, or lungs, an embolism may accordingly cause a heart attack, a stroke, or a pulmonary embolism. These are medical emergencies. Among the many known biochemical activities of aspirin is its role as an anticoagulant. Aspirin (acetylsalicylic acid) is very effective at inhibiting the aggregation of platelets. It is routinely administered during a heart attack or stroke to reduce the adverse effects. Physicians sometimes recommend that patients at risk for cardiovascular disease take a low dose of aspirin on a daily basis as a preventive measure. However, aspirin can also lead to serious side effects, including increasing the risk of ulcers. A patient is well advised to consult a physician before beginning any aspirin regimen. A class of drugs collectively known as thrombolytic agents can help speed up the degradation of an abnormal clot. If a thrombolytic agent is administered to a patient within 3 hours following a thrombotic stroke, the patient's prognosis improves significantly. However, some strokes are not caused by thrombi, but by hemorrhage. Thus, the cause must be determined before treatment begins. Tissue plasminogen activator is an enzyme that catalyzes the conversion of plasminogen to plasmin, the primary enzyme that breaks down clots. It is released naturally by endothelial cells but is also used in clinical medicine. New research is progressing using compounds isolated from the venom of some species of snakes, particularly vipers and cobras, which may eventually have therapeutic value as thrombolytic agents.

clotting factors

group of 12 identified substances active in coagulation

deoxyhemoglobin

molecule of hemoglobin without an oxygen molecule bound to it

Heart: Broken Heart Syndrome

Extreme stress from such life events as the death of a loved one, an emotional break up, loss of income, or foreclosure of a home may lead to a condition commonly referred to as broken heart syndrome. This condition may also be called Takotsubo cardiomyopathy, transient apical ballooning syndrome, apical ballooning cardiomyopathy, stress-induced cardiomyopathy, Gebrochenes-Herz syndrome, and stress cardiomyopathy. The recognized effects on the heart include congestive heart failure due to a profound weakening of the myocardium not related to lack of oxygen. This may lead to acute heart failure, lethal arrhythmias, or even the rupture of a ventricle. The exact etiology is not known, but several factors have been suggested, including transient vasospasm, dysfunction of the cardiac capillaries, or thickening of the myocardium—particularly in the left ventricle—that may lead to the critical circulation of blood to this region. While many patients survive the initial acute event with treatment to restore normal function, there is a strong correlation with death. Careful statistical analysis by the Cass Business School, a prestigious institution located in London, published in 2008, revealed that within one year of the death of a loved one, women are more than twice as likely to die and males are six times as likely to die as would otherwise be expected.

Major Factors Increasing Heart Rate and Force of Contraction

Factor Effect Cardioaccelerator nerves Release of norepinephrine by cardioaccelerator nerves Proprioreceptors Increased firing rates of proprioreceptors (e.g. during exercise) Chemoreceptors Chemoreceptors sensing decreased levels of O2 or increased levels of H+, CO2 and lactic acid Baroreceptors Decreased firing rates of baroreceptors (indicating falling blood volume/pressure) Limbic system Anticipation of physical exercise or strong emotions by the limbic system Catecholamines Increased epinephrine and norepinephrine release by the adrenal glands Thyroid hormones Increased T3 and T4 in the blood (released by thyroid) Calcium Increase in calcium ions in the blood Potassium Decrease in potassium ions in the blood Sodium Decrease in sodium ions in the blood Body temperature Increase in body temperature Nicotine and caffeine Presence of nicotine, caffeine or other stimulants

Factors Decreasing Heart Rate and Force of Contraction

Factor Effect Cardioinhibitor nerves (vagus) Release of acetylcholine by cardioaccelerator nerves Proprioreceptors Decreased firing rates of proprioreceptors (e.g. during rest) Chemoreceptors Chemoreceptors sensing increased levels of O2 or decreased levels of H+, CO2 and lactic acid Baroreceptors Increased firing rates of baroreceptors (indicating rising blood volume/pressure) Limbic system Anticipation of relaxation by the limbic system Catecholamines Increased epinephrine and norepinephrine release by the adrenal glands Thyroid hormones Decreased T3 and T4 in the blood (released by thyroid) Calcium Increase in calcium ions in the blood Potassium Increase in potassium ions in the blood Sodium Increase in sodium ions in the blood Body temperature Decrease in body temperature Opiates and tranquilizers Presence of opiates (heroin), tranquilizers or other depressants

True or false: The buffy coat is the portion of a blood sample that is made up of its proteins.

False. The buffy coat is the portion of blood that is made up of its leukocytes and platelets.

Pressures and Flow

Fluids, whether gases or liquids, are materials that flow according to pressure gradients—that is, they move from regions that are higher in pressure to regions that are lower in pressure. Accordingly, when the heart chambers are relaxed (diastole), blood will flow into the atria from the veins, which are higher in pressure. As blood flows into the atria, the pressure will rise, so the blood will initially move passively from the atria into the ventricles. When the action potential triggers the muscles in the atria to contract (atrial systole), the pressure within the atria rises further, pumping blood into the ventricles. During ventricular systole, pressure rises in the ventricles, pumping blood into the pulmonary trunk from the right ventricle and into the aorta from the left ventricle. Again, as you consider this flow and relate it to the conduction pathway, the elegance of the system should become apparent.

Heart: Abnormal Heart Rates

For an adult, normal resting HR will be in the range of 60-100 bpm. Bradycardia is the condition in which resting rate drops below 60 bpm, and tachycardia is the condition in which the resting rate is above 100 bpm. Trained athletes typically have very low HRs. If the patient is not exhibiting other symptoms, such as weakness, fatigue, dizziness, fainting, chest discomfort, palpitations, or respiratory distress, bradycardia is not considered clinically significant. However, if any of these symptoms are present, they may indicate that the heart is not providing sufficient oxygenated blood to the tissues. The term relative bradycardia may be used with a patient who has a HR in the normal range but is still suffering from these symptoms. Most patients remain asymptomatic as long as the HR remains above 50 bpm. Bradycardia may be caused by either inherent factors or causes external to the heart. While the condition may be inherited, typically it is acquired in older individuals. Inherent causes include abnormalities in either the SA or AV node. If the condition is serious, a pacemaker may be required. Other causes include ischemia to the heart muscle or diseases of the heart vessels or valves. External causes include metabolic disorders, pathologies of the endocrine system often involving the thyroid, electrolyte imbalances, neurological disorders including inappropriate autonomic responses, autoimmune pathologies, over-prescription of beta blocker drugs that reduce HR, recreational drug use, or even prolonged bed rest. Treatment relies upon establishing the underlying cause of the disorder and may necessitate supplemental oxygen. Tachycardia is not normal in a resting patient but may be detected in pregnant women or individuals experiencing extreme stress. In the latter case, it would likely be triggered by stimulation from the limbic system or disorders of the autonomic nervous system. In some cases, tachycardia may involve only the atria. Some individuals may remain asymptomatic, but when present, symptoms may include dizziness, shortness of breath, lightheadedness, rapid pulse, heart palpations, chest pain, or fainting (syncope). While tachycardia is defined as a HR above 100 bpm, there is considerable variation among people. Further, the normal resting HRs of children are often above 100 bpm, but this is not considered to be tachycardia Many causes of tachycardia may be benign, but the condition may also be correlated with fever, anemia, hypoxia, hyperthyroidism, hypersecretion of catecholamines, some cardiomyopathies, some disorders of the valves, and acute exposure to radiation. Elevated rates in an exercising or resting patient are normal and expected. Resting rate should always be taken after recovery from exercise. Treatment depends upon the underlying cause but may include medications, implantable cardioverter defibrillators, ablation, or surgery.

How do gap junctions and intercalated disks aid contraction of the heart?

Gap junctions within the intercalated disks allow impulses to spread from one cardiac muscle cell to another, allowing sodium, potassium, and calcium ions to flow between adjacent cells, propagating the action potential, and ensuring coordinated contractions.

Erythrocytes live up to 120 days in the circulation, after which the worn-out cells are removed by a type of myeloid phagocytic cell called a macrophage, located primarily within the bone marrow, liver, and spleen. The components of the degraded erythrocytes' hemoglobin are further processed as follows:

Globin, the protein portion of hemoglobin, is broken down into amino acids, which can be sent back to the bone marrow to be used in the production of new erythrocytes. Hemoglobin that is not phagocytized is broken down in the circulation, releasing alpha and beta chains that are removed from circulation by the kidneys. The iron contained in the heme portion of hemoglobin may be stored in the liver or spleen, primarily in the form of ferritin or hemosiderin, or carried through the bloodstream by transferrin to the red bone marrow for recycling into new erythrocytes. The non-iron portion of heme is degraded into the waste product biliverdin, a green pigment, and then into another waste product, bilirubin, a yellow pigment. Bilirubin binds to albumin and travels in the blood to the liver, which uses it in the manufacture of bile, a compound released into the intestines to help emulsify dietary fats. In the large intestine, bacteria breaks the bilirubin apart from the bile and converts it to urobilinogen and then into stercobilin. It is then eliminated from the body in the feces. Broad-spectrum antibiotics typically eliminate these bacteria as well and may alter the color of feces. The kidneys also remove any circulating bilirubin and other related metabolic byproducts such as urobilins and secrete them into the urine.

Factors Decreasing Heart Rate

HR can be slowed when a person experiences altered sodium and potassium levels, hypoxia, acidosis, alkalosis, and hypothermia (see Table). The relationship between electrolytes and HR is complex, but maintaining electrolyte balance is critical to the normal wave of depolarization. Of the two ions, potassium has the greater clinical significance. Initially, both hyponatremia (low sodium levels) and hypernatremia (high sodium levels) may lead to tachycardia. Severely high hypernatremia may lead to fibrillation, which may cause CO to cease. Severe hyponatremia leads to both bradycardia and other arrhythmias. Hypokalemia (low potassium levels) also leads to arrhythmias, whereas hyperkalemia (high potassium levels) causes the heart to become weak and flaccid, and ultimately to fail. Acidosis is a condition in which excess hydrogen ions are present, and the patient's blood expresses a low pH value. Alkalosis is a condition in which there are too few hydrogen ions, and the patient's blood has an elevated pH. Normal blood pH falls in the range of 7.35-7.45, so a number lower than this range represents acidosis and a higher number represents alkalosis. Recall that enzymes are the regulators or catalysts of virtually all biochemical reactions; they are sensitive to pH and will change shape slightly with values outside their normal range. These variations in pH and accompanying slight physical changes to the active site on the enzyme decrease the rate of formation of the enzyme-substrate complex, subsequently decreasing the rate of many enzymatic reactions, which can have complex effects on HR. Severe changes in pH will lead to denaturation of the enzyme. The last variable is body temperature. Elevated body temperature is called hyperthermia, and suppressed body temperature is called hypothermia. Slight hyperthermia results in increasing HR and strength of contraction. Hypothermia slows the rate and strength of heart contractions. This distinct slowing of the heart is one component of the larger diving reflex that diverts blood to essential organs while submerged. If sufficiently chilled, the heart will stop beating, a technique that may be employed during open heart surgery. In this case, the patient's blood is normally diverted to an artificial heart-lung machine to maintain the body's blood supply and gas exchange until the surgery is complete, and sinus rhythm can be restored. Excessive hyperthermia and hypothermia will both result in death, as enzymes drive the body systems to cease normal function, beginning with the central nervous system.

Heart Rates

HRs vary considerably, not only with exercise and fitness levels, but also with age. Newborn resting HRs may be 120 bpm. HR gradually decreases until young adulthood and then gradually increases again with age. Maximum HRs are normally in the range of 200-220 bpm, although there are some extreme cases in which they may reach higher levels. As one ages, the ability to generate maximum rates decreases. This may be estimated by taking the maximal value of 220 bpm and subtracting the individual's age. So a 40-year-old individual would be expected to hit a maximum rate of approximately 180, and a 60-year-old person would achieve a HR of 160.

Hemoglobin

Hemoglobin is a large molecule made up of proteins and iron. It consists of four folded chains of a protein called globin, designated alpha 1 and 2, and beta 1 and 2 (Figurea). Each of these globin molecules is bound to a red pigment molecule called heme, which contains an ion of iron (Fe2+) (Figureb). Each iron ion in the heme can bind to one oxygen molecule; therefore, each hemoglobin molecule can transport four oxygen molecules. An individual erythrocyte may contain about 300 million hemoglobin molecules, and therefore can bind to and transport up to 1.2 billion oxygen molecules (see Figureb).

tissue factor

protein thromboplastin, which initiates the extrinsic pathway when released in response to tissue damage

Conduction System of the Heart

If embryonic heart cells are separated into a Petri dish and kept alive, each is capable of generating its own electrical impulse followed by contraction. When two independently beating embryonic cardiac muscle cells are placed together, the cell with the higher inherent rate sets the pace, and the impulse spreads from the faster to the slower cell to trigger a contraction. As more cells are joined together, the fastest cell continues to assume control of the rate. A fully developed adult heart maintains the capability of generating its own electrical impulse, triggered by the fastest cells, as part of the cardiac conduction system. The components of the cardiac conduction system include the sinoatrial node, the atrioventricular node, the atrioventricular bundle, the atrioventricular bundle branches, and the Purkinje cells (Figure).

Heart: Cardiac Tamponade

If excess fluid builds within the pericardial space, it can lead to a condition called cardiac tamponade, or pericardial tamponade. With each contraction of the heart, more fluid—in most instances, blood—accumulates within the pericardial cavity. In order to fill with blood for the next contraction, the heart must relax. However, the excess fluid in the pericardial cavity puts pressure on the heart and prevents full relaxation, so the chambers within the heart contain slightly less blood as they begin each heart cycle. Over time, less and less blood is ejected from the heart. If the fluid builds up slowly, as in hypothyroidism, the pericardial cavity may be able to expand gradually to accommodate this extra volume. Some cases of fluid in excess of one liter within the pericardial cavity have been reported. Rapid accumulation of as little as 100 mL of fluid following trauma may trigger cardiac tamponade. Other common causes include myocardial rupture, pericarditis, cancer, or even cardiac surgery. Removal of this excess fluid requires insertion of drainage tubes into the pericardial cavity. Premature removal of these drainage tubes, for example, following cardiac surgery, or clot formation within these tubes are causes of this condition. Untreated, cardiac tamponade can lead to death.

CPR technique

If the heart should stop, CPR can maintain the flow of blood until the heart resumes beating. By applying pressure to the sternum, the blood within the heart will be squeezed out of the heart and into the circulation. Proper positioning of the hands on the sternum to perform CPR would be between the lines at T4 and T9.

Standard Placement of ECG Leads

In a 12-lead ECG, six electrodes are placed on the chest, and four electrodes are placed on the limbs.

Explain why administration of a thrombolytic agent is a first intervention for someone who has suffered a thrombotic stroke.

In a thrombotic stroke, a blood vessel to the brain has been blocked by a thrombus, an aggregation of platelets and erythrocytes within a blood vessel. A thrombolytic agent is a medication that promotes the breakup of thrombi.

Other Plasma Solutes

In addition to proteins, plasma contains a wide variety of other substances. These include various electrolytes, such as sodium, potassium, and calcium ions; dissolved gases, such as oxygen, carbon dioxide, and nitrogen; various organic nutrients, such as vitamins, lipids, glucose, and amino acids; and metabolic wastes. All of these nonprotein solutes combined contribute approximately 1 percent to the total volume of plasma.

Following a motor vehicle accident, a patient is rushed to the emergency department with multiple traumatic injuries, causing severe bleeding. The patient's condition is critical, and there is no time for determining his blood type. What type of blood is transfused, and why?

In emergency situations, blood type O− will be infused until cross matching can be done. Blood type O− is called the universal donor blood because the erythrocytes have neither A nor B antigens on their surface, and the Rh factor is negative.

Basophils are the least common leukocytes, typically comprising less than one percent of the total leukocyte count. They are slightly smaller than neutrophils and eosinophils at 8-10 µm in diameter. The granules of basophils stain best with basic (alkaline) stains. Basophils contain large granules that pick up a dark blue stain and are so common they may make it difficult to see the two-lobed nucleus.

In general, basophils intensify the inflammatory response. They share this trait with mast cells. In the past, mast cells were considered to be basophils that left the circulation. However, this appears not to be the case, as the two cell types develop from different lineages. The granules of basophils release histamines, which contribute to inflammation, and heparin, which opposes blood clotting. High counts of basophils are associated with allergies, parasitic infections, and hypothyroidism. Low counts are associated with pregnancy, stress, and hyperthyroidism.

Thyroid Hormones

In general, increased levels of thyroid hormone, or thyroxin, increase cardiac rate and contractility. The impact of thyroid hormone is typically of a much longer duration than that of the catecholamines. The physiologically active form of thyroid hormone, T3 or triiodothyronine, has been shown to directly enter cardiomyocytes and alter activity at the level of the genome. It also impacts the beta adrenergic response similar to epinephrine and NE described above. Excessive levels of thyroxin may trigger tachycardia.

Exercise and Maximum Cardiac Output

In healthy young individuals, HR may increase to 150 bpm during exercise. SV can also increase from 70 to approximately 130 mL due to increased strength of contraction. This would increase CO to approximately 19.5 L/min, 4-5 times the resting rate. Top cardiovascular athletes can achieve even higher levels. At their peak performance, they may increase resting CO by 7-8 times. Since the heart is a muscle, exercising it increases its efficiency. The difference between maximum and resting CO is known as the cardiac reserve. It measures the residual capacity of the heart to pump blood.

Blood Doping

In its original intent, the term blood doping was used to describe the practice of injecting by transfusion supplemental RBCs into an individual, typically to enhance performance in a sport. Additional RBCs would deliver more oxygen to the tissues, providing extra aerobic capacity, clinically referred to as VO2 max. The source of the cells was either from the recipient (autologous) or from a donor with compatible blood (homologous). This practice was aided by the well-developed techniques of harvesting, concentrating, and freezing of the RBCs that could be later thawed and injected, yet still retain their functionality. These practices are considered illegal in virtually all sports and run the risk of infection, significantly increasing the viscosity of the blood and the potential for transmission of blood-borne pathogens if the blood was collected from another individual. With the development of synthetic EPO in the 1980s, it became possible to provide additional RBCs by artificially stimulating RBC production in the bone marrow. Originally developed to treat patients suffering from anemia, renal failure, or cancer treatment, large quantities of EPO can be generated by recombinant DNA technology. Synthetic EPO is injected under the skin and can increase hematocrit for many weeks. It may also induce polycythemia and raise hematocrit to 70 or greater. This increased viscosity raises the resistance of the blood and forces the heart to pump more powerfully; in extreme cases, it has resulted in death. Other drugs such as cobalt II chloride have been shown to increase natural EPO gene expression. Blood doping has become problematic in many sports, especially cycling. Lance Armstrong, winner of seven Tour de France and many other cycling titles, was stripped of his victories and admitted to blood doping in 2013.

ferritin

protein-containing storage form of iron found in the bone marrow, liver, and spleen

Clotting Factors Involved in Coagulation

In the coagulation cascade, chemicals called clotting factors (or coagulation factors) prompt reactions that activate still more coagulation factors. The process is complex, but is initiated along two basic pathways: The extrinsic pathway, which normally is triggered by trauma. The intrinsic pathway, which begins in the bloodstream and is triggered by internal damage to the wall of the vessel. Both of these merge into a third pathway, referred to as the common pathway (see Figureb). All three pathways are dependent upon the 12 known clotting factors, including Ca2+ and vitamin K (Table). Clotting factors are secreted primarily by the liver and the platelets. The liver requires the fat-soluble vitamin K to produce many of them. Vitamin K (along with biotin and folate) is somewhat unusual among vitamins in that it is not only consumed in the diet but is also synthesized by bacteria residing in the large intestine. The calcium ion, considered factor IV, is derived from the diet and from the breakdown of bone. Some recent evidence indicates that activation of various clotting factors occurs on specific receptor sites on the surfaces of platelets. The 12 clotting factors are numbered I through XIII according to the order of their discovery. Factor VI was once believed to be a distinct clotting factor, but is now thought to be identical to factor V. Rather than renumber the other factors, factor VI was allowed to remain as a placeholder and also a reminder that knowledge changes over time.

External Automated Defibrillators

In the event that the electrical activity of the heart is severely disrupted, cessation of electrical activity or fibrillation may occur. In fibrillation, the heart beats in a wild, uncontrolled manner, which prevents it from being able to pump effectively. Atrial fibrillation (see Figureb) is a serious condition, but as long as the ventricles continue to pump blood, the patient's life may not be in immediate danger. Ventricular fibrillation (see Figured) is a medical emergency that requires life support, because the ventricles are not effectively pumping blood. In a hospital setting, it is often described as "code blue." If untreated for as little as a few minutes, ventricular fibrillation may lead to brain death. The most common treatment is defibrillation, which uses special paddles to apply a charge to the heart from an external electrical source in an attempt to establish a normal sinus rhythm (Figure). A defibrillator effectively stops the heart so that the SA node can trigger a normal conduction cycle. Because of their effectiveness in reestablishing a normal sinus rhythm, external automated defibrillators (EADs) are being placed in areas frequented by large numbers of people, such as schools, restaurants, and airports. These devices contain simple and direct verbal instructions that can be followed by nonmedical personnel in an attempt to save a life.

Formation of the Platelet Plug

In the second step, platelets, which normally float free in the plasma, encounter the area of vessel rupture with the exposed underlying connective tissue and collagenous fibers. The platelets begin to clump together, become spiked and sticky, and bind to the exposed collagen and endothelial lining. This process is assisted by a glycoprotein in the blood plasma called von Willebrand factor, which helps stabilize the growing platelet plug. As platelets collect, they simultaneously release chemicals from their granules into the plasma that further contribute to hemostasis. Among the substances released by the platelets are: adenosine diphosphate (ADP), which helps additional platelets to adhere to the injury site, reinforcing and expanding the platelet plug serotonin, which maintains vasoconstriction prostaglandins and phospholipids, which also maintain vasoconstriction and help to activate further clotting chemicals, as discussed next A platelet plug can temporarily seal a small opening in a blood vessel. Plug formation, in essence, buys the body time while more sophisticated and durable repairs are being made. In a similar manner, even modern naval warships still carry an assortment of wooden plugs to temporarily repair small breaches in their hulls until permanent repairs can be made.

This artist's conception of the human heart suggests a powerful engine—not inappropriate for a muscular pump that keeps the body continually supplied with blood. (credit: Patrick J. Lynch)

In this chapter, you will explore the remarkable pump that propels the blood into the vessels. There is no single better word to describe the function of the heart other than "pump," since its contraction develops the pressure that ejects blood into the major vessels: the aorta and pulmonary trunk. From these vessels, the blood is distributed to the remainder of the body. Although the connotation of the term "pump" suggests a mechanical device made of steel and plastic, the anatomical structure is a living, sophisticated muscle. As you read this chapter, try to keep these twin concepts in mind: pump and muscle. Although the term "heart" is an English word, cardiac (heart-related) terminology can be traced back to the Latin term, "kardia." Cardiology is the study of the heart, and cardiologists are the physicians who deal primarily with the heart.

Atherosclerotic Coronary Arteries

In this coronary angiogram (X-ray), the dye makes visible two occluded coronary arteries. Such blockages can lead to decreased blood flow (ischemia) and insufficient oxygen (hypoxia) delivered to the cardiac tissues. If uncorrected, this can lead to cardiac muscle death (myocardial infarction).

Chordae Tendineae and Papillary Muscles

In this frontal section, you can see papillary muscles attached to the tricuspid valve on the right as well as the mitral valve on the left via chordae tendineae. (credit: modification of work by "PV KS"/flickr.com)

Heart Sounds and the Cardiac Cycle

In this illustration, the x-axis reflects time with a recording of the heart sounds. The y-axis represents pressure.

intercalated disc

physical junction between adjacent cardiac muscle cells; consisting of desmosomes, specialized linking proteoglycans, and gap junctions that allow passage of ions between the two cells

Why does increasing EDV increase contractility?

Increasing EDV increases the sarcomeres' lengths within the cardiac muscle cells, allowing more cross bridge formation between the myosin and actin and providing for a more powerful contraction. This relationship is described in the Frank-Starling mechanism.

hemostasis

physiological process by which bleeding ceases

Relationship between the Cardiac Cycle and ECG

Initially, both the atria and ventricles are relaxed (diastole). The P wave represents depolarization of the atria and is followed by atrial contraction (systole). Atrial systole extends until the QRS complex, at which point, the atria relax. The QRS complex represents depolarization of the ventricles and is followed by ventricular contraction. The T wave represents the repolarization of the ventricles and marks the beginning of ventricular relaxation.

Correlation Between Heart Rates and Cardiac Output

Initially, physiological conditions that cause HR to increase also trigger an increase in SV. During exercise, the rate of blood returning to the heart increases. However as the HR rises, there is less time spent in diastole and consequently less time for the ventricles to fill with blood. Even though there is less filling time, SV will initially remain high. However, as HR continues to increase, SV gradually decreases due to decreased filling time. CO will initially stabilize as the increasing HR compensates for the decreasing SV, but at very high rates, CO will eventually decrease as increasing rates are no longer able to compensate for the decreasing SV. Consider this phenomenon in a healthy young individual. Initially, as HR increases from resting to approximately 120 bpm, CO will rise. As HR increases from 120 to 160 bpm, CO remains stable, since the increase in rate is offset by decreasing ventricular filling time and, consequently, SV. As HR continues to rise above 160 bpm, CO actually decreases as SV falls faster than HR increases. So although aerobic exercises are critical to maintain the health of the heart, individuals are cautioned to monitor their HR to ensure they stay within the target heart rate range of between 120 and 160 bpm, so CO is maintained. The target HR is loosely defined as the range in which both the heart and lungs receive the maximum benefit from the aerobic workout and is dependent upon age.

Surface Features of the Heart

Inside the pericardium, the surface features of the heart are visible, including the four chambers. There is a superficial leaf-like extension of the atria near the superior surface of the heart, one on each side, called an auricle—a name that means "ear like"—because its shape resembles the external ear of a human (Figure). Auricles are relatively thin-walled structures that can fill with blood and empty into the atria or upper chambers of the heart. You may also hear them referred to as atrial appendages. Also prominent is a series of fat-filled grooves, each of which is known as a sulcus (plural = sulci), along the superior surfaces of the heart. Major coronary blood vessels are located in these sulci. The deep coronary sulcus is located between the atria and ventricles. Located between the left and right ventricles are two additional sulci that are not as deep as the coronary sulcus. The anterior interventricular sulcus is visible on the anterior surface of the heart, whereas the posterior interventricular sulcus is visible on the posterior surface of the heart. Figure illustrates anterior and posterior views of the surface of the heart.

hemosiderin

protein-containing storage form of iron found in the bone marrow, liver, and spleen

In a healthy young adult, what happens to cardiac output when heart rate increases above 160 bpm?

It decreases.

How does the delay of the impulse at the atrioventricular node contribute to cardiac function?

It ensures sufficient time for the atrial muscle to contract and pump blood into the ventricles prior to the impulse being conducted into the lower chambers.

Which of the following statements about erythropoietin is true?

It facilitates the proliferation and differentiation of the erythrocyte lineage.

What happens to preload when there is venous constriction in the veins?

It increases.

Which of the following statements about albumin is true?

It is the most abundant plasma protein.

Contractility

It is virtually impossible to consider preload or ESV without including an early mention of the concept of contractility. Indeed, the two parameters are intimately linked. Contractility refers to the force of the contraction of the heart muscle, which controls SV, and is the primary parameter for impacting ESV. The more forceful the contraction is, the greater the SV and smaller the ESV are. Less forceful contractions result in smaller SVs and larger ESVs. Factors that increase contractility are described as positive inotropic factors, and those that decrease contractility are described as negative inotropic factors (ino- = "fiber;" -tropic = "turning toward"). Not surprisingly, sympathetic stimulation is a positive inotrope, whereas parasympathetic stimulation is a negative inotrope. Sympathetic stimulation triggers the release of NE at the neuromuscular junction from the cardiac nerves and also stimulates the adrenal cortex to secrete epinephrine and NE. In addition to their stimulatory effects on HR, they also bind to both alpha and beta receptors on the cardiac muscle cell membrane to increase metabolic rate and the force of contraction. This combination of actions has the net effect of increasing SV and leaving a smaller residual ESV in the ventricles. In comparison, parasympathetic stimulation releases ACh at the neuromuscular junction from the vagus nerve. The membrane hyperpolarizes and inhibits contraction to decrease the strength of contraction and SV, and to raise ESV. Since parasympathetic fibers are more widespread in the atria than in the ventricles, the primary site of action is in the upper chambers. Parasympathetic stimulation in the atria decreases the atrial kick and reduces EDV, which decreases ventricular stretch and preload, thereby further limiting the force of ventricular contraction. Stronger parasympathetic stimulation also directly decreases the force of contraction of the ventricles. Several synthetic drugs, including dopamine and isoproterenol, have been developed that mimic the effects of epinephrine and NE by stimulating the influx of calcium ions from the extracellular fluid. Higher concentrations of intracellular calcium ions increase the strength of contraction. Excess calcium (hypercalcemia) also acts as a positive inotropic agent. The drug digitalis lowers HR and increases the strength of the contraction, acting as a positive inotropic agent by blocking the sequestering of calcium ions into the sarcoplasmic reticulum. This leads to higher intracellular calcium levels and greater strength of contraction. In addition to the catecholamines from the adrenal medulla, other hormones also demonstrate positive inotropic effects. These include thyroid hormones and glucagon from the pancreas. Negative inotropic agents include hypoxia, acidosis, hyperkalemia, and a variety of synthetic drugs. These include numerous beta blockers and calcium channel blockers. Early beta blocker drugs include propranolol and pronethalol, and are credited with revolutionizing treatment of cardiac patients experiencing angina pectoris. There is also a large class of dihydropyridine, phenylalkylamine, and benzothiazepine calcium channel blockers that may be administered decreasing the strength of contraction and SV.

Why is the plateau phase so critical to cardiac muscle function?

It prevents additional impulses from spreading through the heart prematurely, thereby allowing the muscle sufficient time to contract and pump blood effectively.

Disorders of Leukocytes

Leukopenia is a condition in which too few leukocytes are produced. If this condition is pronounced, the individual may be unable to ward off disease. Excessive leukocyte proliferation is known as leukocytosis. Although leukocyte counts are high, the cells themselves are often nonfunctional, leaving the individual at increased risk for disease. Leukemia is a cancer involving an abundance of leukocytes. It may involve only one specific type of leukocyte from either the myeloid line (myelocytic leukemia) or the lymphoid line (lymphocytic leukemia). In chronic leukemia, mature leukocytes accumulate and fail to die. In acute leukemia, there is an overproduction of young, immature leukocytes. In both conditions the cells do not function properly. Lymphoma is a form of cancer in which masses of malignant T and/or B lymphocytes collect in lymph nodes, the spleen, the liver, and other tissues. As in leukemia, the malignant leukocytes do not function properly, and the patient is vulnerable to infection. Some forms of lymphoma tend to progress slowly and respond well to treatment. Others tend to progress quickly and require aggressive treatment, without which they are rapidly fatal.

Blood Plasma

Like other fluids in the body, plasma is composed primarily of water: In fact, it is about 92 percent water. Dissolved or suspended within this water is a mixture of substances, most of which are proteins. There are literally hundreds of substances dissolved or suspended in the plasma, although many of them are found only in very small quantities.

Hemopoiesis begins when the hemopoietic stem cell is exposed to appropriate chemical stimuli collectively called hemopoietic growth factors, which prompt it to divide and differentiate. One daughter cell remains a hemopoietic stem cell, allowing hemopoiesis to continue. The other daughter cell becomes either of two types of more specialized stem cells (Figure):

Lymphoid stem cells give rise to a class of leukocytes known as lymphocytes, which include the various T cells, B cells, and natural killer (NK) cells, all of which function in immunity. However, hemopoiesis of lymphocytes progresses somewhat differently from the process for the other formed elements. In brief, lymphoid stem cells quickly migrate from the bone marrow to lymphatic tissues, including the lymph nodes, spleen, and thymus, where their production and differentiation continues. B cells are so named since they mature in the bone marrow, while T cells mature in the thymus. Myeloid stem cells give rise to all the other formed elements, including the erythrocytes; megakaryocytes that produce platelets; and a myeloblast lineage that gives rise to monocytes and three forms of granular leukocytes: neutrophils, eosinophils, and basophils. Lymphoid and myeloid stem cells do not immediately divide and differentiate into mature formed elements. As you can see in Figure, there are several intermediate stages of precursor cells (literally, forerunner cells), many of which can be recognized by their names, which have the suffix -blast. For instance, megakaryoblasts are the precursors of megakaryocytes, and proerythroblasts become reticulocytes, which eject their nucleus and most other organelles before maturing into erythrocytes.

Stroke Volume

Many of the same factors that regulate HR also impact cardiac function by altering SV. While a number of variables are involved, SV is ultimately dependent upon the difference between EDV and ESV. The three primary factors to consider are preload, or the stretch on the ventricles prior to contraction; the contractility, or the force or strength of the contraction itself; and afterload, the force the ventricles must generate to pump blood against the resistance in the vessels. These factors are summarized in Table and Table.

Defense

Many types of WBCs protect the body from external threats, such as disease-causing bacteria that have entered the bloodstream in a wound. Other WBCs seek out and destroy internal threats, such as cells with mutated DNA that could multiply to become cancerous, or body cells infected with viruses. When damage to the vessels results in bleeding, blood platelets and certain proteins dissolved in the plasma, the fluid portion of the blood, interact to block the ruptured areas of the blood vessels involved. This protects the body from further blood loss.

Vitamin-deficient anemias generally involve insufficient vitamin B12 and folate.

Megaloblastic anemia involves a deficiency of vitamin B12 and/or folate, and often involves diets deficient in these essential nutrients. Lack of meat or a viable alternate source, and overcooking or eating insufficient amounts of vegetables may lead to a lack of folate. Pernicious anemia is caused by poor absorption of vitamin B12 and is often seen in patients with Crohn's disease (a severe intestinal disorder often treated by surgery), surgical removal of the intestines or stomach (common in some weight loss surgeries), intestinal parasites, and AIDS. Pregnancies, some medications, excessive alcohol consumption, and some diseases such as celiac disease are also associated with vitamin deficiencies. It is essential to provide sufficient folic acid during the early stages of pregnancy to reduce the risk of neurological defects, including spina bifida, a failure of the neural tube to close.

Lifecycle of Leukocytes

Most leukocytes have a relatively short lifespan, typically measured in hours or days. Production of all leukocytes begins in the bone marrow under the influence of CSFs and interleukins. Secondary production and maturation of lymphocytes occurs in specific regions of lymphatic tissue known as germinal centers. Lymphocytes are fully capable of mitosis and may produce clones of cells with identical properties. This capacity enables an individual to maintain immunity throughout life to many threats that have been encountered in the past.

Heart: Myocardial Infarction

Myocardial infarction (MI) is the formal term for what is commonly referred to as a heart attack. It normally results from a lack of blood flow (ischemia) and oxygen (hypoxia) to a region of the heart, resulting in death of the cardiac muscle cells. An MI often occurs when a coronary artery is blocked by the buildup of atherosclerotic plaque consisting of lipids, cholesterol and fatty acids, and white blood cells, primarily macrophages. It can also occur when a portion of an unstable atherosclerotic plaque travels through the coronary arterial system and lodges in one of the smaller vessels. The resulting blockage restricts the flow of blood and oxygen to the myocardium and causes death of the tissue. MIs may be triggered by excessive exercise, in which the partially occluded artery is no longer able to pump sufficient quantities of blood, or severe stress, which may induce spasm of the smooth muscle in the walls of the vessel. In the case of acute MI, there is often sudden pain beneath the sternum (retrosternal pain) called angina pectoris, often radiating down the left arm in males but not in female patients. Until this anomaly between the sexes was discovered, many female patients suffering MIs were misdiagnosed and sent home. In addition, patients typically present with difficulty breathing and shortness of breath (dyspnea), irregular heartbeat (palpations), nausea and vomiting, sweating (diaphoresis), anxiety, and fainting (syncope), although not all of these symptoms may be present. Many of the symptoms are shared with other medical conditions, including anxiety attacks and simple indigestion, so differential diagnosis is critical. It is estimated that between 22 and 64 percent of MIs present without any symptoms. An MI can be confirmed by examining the patient's ECG, which frequently reveals alterations in the ST and Q components. Some classification schemes of MI are referred to as ST-elevated MI (STEMI) and non-elevated MI (non-STEMI). In addition, echocardiography or cardiac magnetic resonance imaging may be employed. Common blood tests indicating an MI include elevated levels of creatine kinase MB (an enzyme that catalyzes the conversion of creatine to phosphocreatine, consuming ATP) and cardiac troponin (the regulatory protein for muscle contraction), both of which are released by damaged cardiac muscle cells. Immediate treatments for MI are essential and include administering supplemental oxygen, aspirin that helps to break up clots, and nitroglycerine administered sublingually (under the tongue) to facilitate its absorption. Despite its unquestioned success in treatments and use since the 1880s, the mechanism of nitroglycerine is still incompletely understood but is believed to involve the release of nitric oxide, a known vasodilator, and endothelium-derived releasing factor, which also relaxes the smooth muscle in the tunica media of coronary vessels. Longer-term treatments include injections of thrombolytic agents such as streptokinase that dissolve the clot, the anticoagulant heparin, balloon angioplasty and stents to open blocked vessels, and bypass surgery to allow blood to pass around the site of blockage. If the damage is extensive, coronary replacement with a donor heart or coronary assist device, a sophisticated mechanical device that supplements the pumping activity of the heart, may be employed. Despite the attention, development of artificial hearts to augment the severely limited supply of heart donors has proven less than satisfactory but will likely improve in the future. MIs may trigger cardiac arrest, but the two are not synonymous. Important risk factors for MI include cardiovascular disease, age, smoking, high blood levels of the low-density lipoprotein (LDL, often referred to as "bad" cholesterol), low levels of high-density lipoprotein (HDL, or "good" cholesterol), hypertension, diabetes mellitus, obesity, lack of physical exercise, chronic kidney disease, excessive alcohol consumption, and use of illegal drugs.

Cardiovascular Centers

Nervous control over HR is centralized within the two paired cardiovascular centers of the medulla oblongata (Figure). The cardioaccelerator regions stimulate activity via sympathetic stimulation of the cardioaccelerator nerves, and the cardioinhibitory centers decrease heart activity via parasympathetic stimulation as one component of the vagus nerve, cranial nerve X. During rest, both centers provide slight stimulation to the heart, contributing to autonomic tone. This is a similar concept to tone in skeletal muscles. Normally, vagal stimulation predominates as, left unregulated, the SA node would initiate a sinus rhythm of approximately 100 bpm. Both sympathetic and parasympathetic stimulations flow through a paired complex network of nerve fibers known as the cardiac plexus near the base of the heart. The cardioaccelerator center also sends additional fibers, forming the cardiac nerves via sympathetic ganglia (the cervical ganglia plus superior thoracic ganglia T1-T4) to both the SA and AV nodes, plus additional fibers to the atria and ventricles. The ventricles are more richly innervated by sympathetic fibers than parasympathetic fibers. Sympathetic stimulation causes the release of the neurotransmitter norepinephrine (NE) at the neuromuscular junction of the cardiac nerves. NE shortens the repolarization period, thus speeding the rate of depolarization and contraction, which results in an increase in HR. It opens chemical- or ligand-gated sodium and calcium ion channels, allowing an influx of positively charged ions. NE binds to the beta-1 receptor. Some cardiac medications (for example, beta blockers) work by blocking these receptors, thereby slowing HR and are one possible treatment for hypertension. Overprescription of these drugs may lead to bradycardia and even stoppage of the heart.

The most common of all the leukocytes, neutrophils will normally comprise 50-70 percent of total leukocyte count. They are 10-12 µm in diameter, significantly larger than erythrocytes. They are called neutrophils because their granules show up most clearly with stains that are chemically neutral (neither acidic nor basic). The granules are numerous but quite fine and normally appear light lilac. The nucleus has a distinct lobed appearance and may have two to five lobes, the number increasing with the age of the cell. Older neutrophils have increasing numbers of lobes and are often referred to as polymorphonuclear (a nucleus with many forms), or simply "polys." Younger and immature neutrophils begin to develop lobes and are known as "bands."

Neutrophils are rapid responders to the site of infection and are efficient phagocytes with a preference for bacteria. Their granules include lysozyme, an enzyme capable of lysing, or breaking down, bacterial cell walls; oxidants such as hydrogen peroxide; and defensins, proteins that bind to and puncture bacterial and fungal plasma membranes, so that the cell contents leak out. Abnormally high counts of neutrophils indicate infection and/or inflammation, particularly triggered by bacteria, but are also found in burn patients and others experiencing unusual stress. A burn injury increases the proliferation of neutrophils in order to fight off infection that can result from the destruction of the barrier of the skin. Low counts may be caused by drug toxicity and other disorders, and may increase an individual's susceptibility to infection.

fibrinogen

plasma protein produced in the liver and involved in blood clotting

Sinoatrial (SA) Node

Normal cardiac rhythm is established by the sinoatrial (SA) node, a specialized clump of myocardial conducting cells located in the superior and posterior walls of the right atrium in close proximity to the orifice of the superior vena cava. The SA node has the highest inherent rate of depolarization and is known as the pacemaker of the heart. It initiates the sinus rhythm, or normal electrical pattern followed by contraction of the heart. This impulse spreads from its initiation in the SA node throughout the atria through specialized internodal pathways, to the atrial myocardial contractile cells and the atrioventricular node. The internodal pathways consist of three bands (anterior, middle, and posterior) that lead directly from the SA node to the next node in the conduction system, the atrioventricular node (see Figure). The impulse takes approximately 50 ms (milliseconds) to travel between these two nodes. The relative importance of this pathway has been debated since the impulse would reach the atrioventricular node simply following the cell-by-cell pathway through the contractile cells of the myocardium in the atria. In addition, there is a specialized pathway called Bachmann's bundle or the interatrial band that conducts the impulse directly from the right atrium to the left atrium. Regardless of the pathway, as the impulse reaches the atrioventricular septum, the connective tissue of the cardiac skeleton prevents the impulse from spreading into the myocardial cells in the ventricles except at the atrioventricular node. Figure illustrates the initiation of the impulse in the SA node that then spreads the impulse throughout the atria to the atrioventricular node. The electrical event, the wave of depolarization, is the trigger for muscular contraction. The wave of depolarization begins in the right atrium, and the impulse spreads across the superior portions of both atria and then down through the contractile cells. The contractile cells then begin contraction from the superior to the inferior portions of the atria, efficiently pumping blood into the ventricles.

Cardiac Muscle Metabolism

Normally, cardiac muscle metabolism is entirely aerobic. Oxygen from the lungs is brought to the heart, and every other organ, attached to the hemoglobin molecules within the erythrocytes. Heart cells also store appreciable amounts of oxygen in myoglobin. Normally, these two mechanisms, circulating oxygen and oxygen attached to myoglobin, can supply sufficient oxygen to the heart, even during peak performance. Fatty acids and glucose from the circulation are broken down within the mitochondria to release energy in the form of ATP. Both fatty acid droplets and glycogen are stored within the sarcoplasm and provide additional nutrient supply. (Seek additional content for more detail about metabolism.)

Transportation

Nutrients from the foods you eat are absorbed in the digestive tract. Most of these travel in the bloodstream directly to the liver, where they are processed and released back into the bloodstream for delivery to body cells. Oxygen from the air you breathe diffuses into the blood, which moves from the lungs to the heart, which then pumps it out to the rest of the body. Moreover, endocrine glands scattered throughout the body release their products, called hormones, into the bloodstream, which carries them to distant target cells. Blood also picks up cellular wastes and byproducts, and transports them to various organs for removal. For instance, blood moves carbon dioxide to the lungs for exhalation from the body, and various waste products are transported to the kidneys and liver for excretion from the body in the form of urine or bile.

The innermost layer of the heart wall, the endocardium, is joined to the myocardium with a thin layer of connective tissue. The endocardium lines the chambers where the blood circulates and covers the heart valves. It is made of simple squamous epithelium called endothelium, which is continuous with the endothelial lining of the blood vessels (see Figure).

Once regarded as a simple lining layer, recent evidence indicates that the endothelium of the endocardium and the coronary capillaries may play active roles in regulating the contraction of the muscle within the myocardium. The endothelium may also regulate the growth patterns of the cardiac muscle cells throughout life, and the endothelins it secretes create an environment in the surrounding tissue fluids that regulates ionic concentrations and states of contractility. Endothelins are potent vasoconstrictors and, in a normal individual, establish a homeostatic balance with other vasoconstrictors and vasodilators.

A single drop of blood contains millions of red blood cells, white blood cells, and platelets.

One of each type is shown here, isolated from a scanning electron micrograph.

Heart Sounds

One of the simplest, yet effective, diagnostic techniques applied to assess the state of a patient's heart is auscultation using a stethoscope. In a normal, healthy heart, there are only two audible heart sounds: S1 and S2. S1 is the sound created by the closing of the atrioventricular valves during ventricular contraction and is normally described as a "lub," or first heart sound. The second heart sound, S2, is the sound of the closing of the semilunar valves during ventricular diastole and is described as a "dub" (Figure). In both cases, as the valves close, the openings within the atrioventricular septum guarded by the valves will become reduced, and blood flow through the opening will become more turbulent until the valves are fully closed. There is a third heart sound, S3, but it is rarely heard in healthy individuals. It may be the sound of blood flowing into the atria, or blood sloshing back and forth in the ventricle, or even tensing of the chordae tendineae. S3 may be heard in youth, some athletes, and pregnant women. If the sound is heard later in life, it may indicate congestive heart failure, warranting further tests. Some cardiologists refer to the collective S1, S2, and S3 sounds as the "Kentucky gallop," because they mimic those produced by a galloping horse. The fourth heart sound, S4, results from the contraction of the atria pushing blood into a stiff or hypertrophic ventricle, indicating failure of the left ventricle. S4 occurs prior to S1 and the collective sounds S4, S1, and S2 are referred to by some cardiologists as the "Tennessee gallop," because of their similarity to the sound produced by a galloping horse with a different gait. A few individuals may have both S3 and S4, and this combined sound is referred to as S7.

Heart: Heart Defects

One very common form of interatrial septum pathology is patent foramen ovale, which occurs when the septum primum does not close at birth, and the fossa ovalis is unable to fuse. The word patent is from the Latin root patens for "open." It may be benign or asymptomatic, perhaps never being diagnosed, or in extreme cases, it may require surgical repair to close the opening permanently. As much as 20-25 percent of the general population may have a patent foramen ovale, but fortunately, most have the benign, asymptomatic version. Patent foramen ovale is normally detected by auscultation of a heart murmur (an abnormal heart sound) and confirmed by imaging with an echocardiogram. Despite its prevalence in the general population, the causes of patent ovale are unknown, and there are no known risk factors. In nonlife-threatening cases, it is better to monitor the condition than to risk heart surgery to repair and seal the opening. Coarctation of the aorta is a congenital abnormal narrowing of the aorta that is normally located at the insertion of the ligamentum arteriosum, the remnant of the fetal shunt called the ductus arteriosus. If severe, this condition drastically restricts blood flow through the primary systemic artery, which is life threatening. In some individuals, the condition may be fairly benign and not detected until later in life. Detectable symptoms in an infant include difficulty breathing, poor appetite, trouble feeding, or failure to thrive. In older individuals, symptoms include dizziness, fainting, shortness of breath, chest pain, fatigue, headache, and nosebleeds. Treatment involves surgery to resect (remove) the affected region or angioplasty to open the abnormally narrow passageway. Studies have shown that the earlier the surgery is performed, the better the chance of survival. A patent ductus arteriosus is a congenital condition in which the ductus arteriosus fails to close. The condition may range from severe to benign. Failure of the ductus arteriosus to close results in blood flowing from the higher pressure aorta into the lower pressure pulmonary trunk. This additional fluid moving toward the lungs increases pulmonary pressure and makes respiration difficult. Symptoms include shortness of breath (dyspnea), tachycardia, enlarged heart, a widened pulse pressure, and poor weight gain in infants. Treatments include surgical closure (ligation), manual closure using platinum coils or specialized mesh inserted via the femoral artery or vein, or nonsteroidal anti-inflammatory drugs to block the synthesis of prostaglandin E2, which maintains the vessel in an open position. If untreated, the condition can result in congestive heart failure. Septal defects are not uncommon in individuals and may be congenital or caused by various disease processes. Tetralogy of Fallot is a congenital condition that may also occur from exposure to unknown environmental factors; it occurs when there is an opening in the interventricular septum caused by blockage of the pulmonary trunk, normally at the pulmonary semilunar valve. This allows blood that is relatively low in oxygen from the right ventricle to flow into the left ventricle and mix with the blood that is relatively high in oxygen. Symptoms include a distinct heart murmur, low blood oxygen percent saturation, dyspnea or difficulty in breathing, polycythemia, broadening (clubbing) of the fingers and toes, and in children, difficulty in feeding or failure to grow and develop. It is the most common cause of cyanosis following birth. The term "tetralogy" is derived from the four components of the condition, although only three may be present in an individual patient: pulmonary infundibular stenosis (rigidity of the pulmonary valve), overriding aorta (the aorta is shifted above both ventricles), ventricular septal defect (opening), and right ventricular hypertrophy (enlargement of the right ventricle). Other heart defects may also accompany this condition, which is typically confirmed by echocardiography imaging. Tetralogy of Fallot occurs in approximately 400 out of one million live births. Normal treatment involves extensive surgical repair, including the use of stents to redirect blood flow and replacement of valves and patches to repair the septal defect, but the condition has a relatively high mortality. Survival rates are currently 75 percent during the first year of life; 60 percent by 4 years of age; 30 percent by 10 years; and 5 percent by 40 years. In the case of severe septal defects, including both tetralogy of Fallot and patent foramen ovale, failure of the heart to develop properly can lead to a condition commonly known as a "blue baby." Regardless of normal skin pigmentation, individuals with this condition have an insufficient supply of oxygenated blood, which leads to cyanosis, a blue or purple coloration of the skin, especially when active. Septal defects are commonly first detected through auscultation, listening to the chest using a stethoscope. In this case, instead of hearing normal heart sounds attributed to the flow of blood and closing of heart valves, unusual heart sounds may be detected. This is often followed by medical imaging to confirm or rule out a diagnosis. In many cases, treatment may not be needed. Some common congenital heart defects are illustrated in Figure.

Which of the following is unique to cardiac muscle cells?

Only cardiac muscle is capable of autorhythmicity

transferrin

plasma protein that binds reversibly to iron and distributes it throughout the body

Membranes, Surface Features, and Layers

Our exploration of more in-depth heart structures begins by examining the membrane that surrounds the heart, the prominent surface features of the heart, and the layers that form the wall of the heart. Each of these components plays its own unique role in terms of function.

Thrombocytes are more accurately called ________.

platelets

Phlebotomy and Medical Lab Technology

Phlebotomists are professionals trained to draw blood (phleb- = "a blood vessel"; -tomy = "to cut"). When more than a few drops of blood are required, phlebotomists perform a venipuncture, typically of a surface vein in the arm. They perform a capillary stick on a finger, an earlobe, or the heel of an infant when only a small quantity of blood is required. An arterial stick is collected from an artery and used to analyze blood gases. After collection, the blood may be analyzed by medical laboratories or perhaps used for transfusions, donations, or research. While many allied health professionals practice phlebotomy, the American Society of Phlebotomy Technicians issues certificates to individuals passing a national examination, and some large labs and hospitals hire individuals expressly for their skill in phlebotomy. Medical or clinical laboratories employ a variety of individuals in technical positions: Medical technologists (MT), also known as clinical laboratory technologists (CLT), typically hold a bachelor's degree and certification from an accredited training program. They perform a wide variety of tests on various body fluids, including blood. The information they provide is essential to the primary care providers in determining a diagnosis and in monitoring the course of a disease and response to treatment. Medical laboratory technicians (MLT) typically have an associate's degree but may perform duties similar to those of an MT. Medical laboratory assistants (MLA) spend the majority of their time processing samples and carrying out routine assignments within the lab. Clinical training is required, but a degree may not be essential to obtaining a position.

Which of the formed elements arise from myeloid stem cells?

platelets

Preload

Preload is another way of expressing EDV. Therefore, the greater the EDV is, the greater the preload is. One of the primary factors to consider is filling time, or the duration of ventricular diastole during which filling occurs. The more rapidly the heart contracts, the shorter the filling time becomes, and the lower the EDV and preload are. This effect can be partially overcome by increasing the second variable, contractility, and raising SV, but over time, the heart is unable to compensate for decreased filling time, and preload also decreases. With increasing ventricular filling, both EDV or preload increase, and the cardiac muscle itself is stretched to a greater degree. At rest, there is little stretch of the ventricular muscle, and the sarcomeres remain short. With increased ventricular filling, the ventricular muscle is increasingly stretched and the sarcomere length increases. As the sarcomeres reach their optimal lengths, they will contract more powerfully, because more of the myosin heads can bind to the actin on the thin filaments, forming cross bridges and increasing the strength of contraction and SV. If this process were to continue and the sarcomeres stretched beyond their optimal lengths, the force of contraction would decrease. However, due to the physical constraints of the location of the heart, this excessive stretch is not a concern. The relationship between ventricular stretch and contraction has been stated in the well-known Frank-Starling mechanism or simply Starling's Law of the Heart. This principle states that, within physiological limits, the force of heart contraction is directly proportional to the initial length of the muscle fiber. This means that the greater the stretch of the ventricular muscle (within limits), the more powerful the contraction is, which in turn increases SV. Therefore, by increasing preload, you increase the second variable, contractility. Otto Frank (1865-1944) was a German physiologist; among his many published works are detailed studies of this important heart relationship. Ernest Starling (1866-1927) was an important English physiologist who also studied the heart. Although they worked largely independently, their combined efforts and similar conclusions have been recognized in the name "Frank-Starling mechanism." Any sympathetic stimulation to the venous system will increase venous return to the heart, which contributes to ventricular filling, and EDV and preload. While much of the ventricular filling occurs while both atria and ventricles are in diastole, the contraction of the atria, the atrial kick, plays a crucial role by providing the last 20-30 percent of ventricular filling.

Sites of Hemopoiesis

Prior to birth, hemopoiesis occurs in a number of tissues, beginning with the yolk sac of the developing embryo, and continuing in the fetal liver, spleen, lymphatic tissue, and eventually the red bone marrow. Following birth, most hemopoiesis occurs in the red marrow, a connective tissue within the spaces of spongy (cancellous) bone tissue. In children, hemopoiesis can occur in the medullary cavity of long bones; in adults, the process is largely restricted to the cranial and pelvic bones, the vertebrae, the sternum, and the proximal epiphyses of the femur and humerus. Throughout adulthood, the liver and spleen maintain their ability to generate the formed elements. This process is referred to as extramedullary hemopoiesis (meaning hemopoiesis outside the medullary cavity of adult bones). When a disease such as bone cancer destroys the bone marrow, causing hemopoiesis to fail, extramedullary hemopoiesis may be initiated.

Lifecycle of Erythrocytes

Production of erythrocytes in the marrow occurs at the staggering rate of more than 2 million cells per second. For this production to occur, a number of raw materials must be present in adequate amounts. These include the same nutrients that are essential to the production and maintenance of any cell, such as glucose, lipids, and amino acids. However, erythrocyte production also requires several trace elements: Iron. We have said that each heme group in a hemoglobin molecule contains an ion of the trace mineral iron. On average, less than 20 percent of the iron we consume is absorbed. Heme iron, from animal foods such as meat, poultry, and fish, is absorbed more efficiently than non-heme iron from plant foods. Upon absorption, iron becomes part of the body's total iron pool. The bone marrow, liver, and spleen can store iron in the protein compounds ferritin and hemosiderin. Ferroportin transports the iron across the intestinal cell plasma membranes and from its storage sites into tissue fluid where it enters the blood. When EPO stimulates the production of erythrocytes, iron is released from storage, bound to transferrin, and carried to the red marrow where it attaches to erythrocyte precursors. Copper. A trace mineral, copper is a component of two plasma proteins, hephaestin and ceruloplasmin. Without these, hemoglobin could not be adequately produced. Located in intestinal villi, hephaestin enables iron to be absorbed by intestinal cells. Ceruloplasmin transports copper. Both enable the oxidation of iron from Fe2+ to Fe3+, a form in which it can be bound to its transport protein, transferrin, for transport to body cells. In a state of copper deficiency, the transport of iron for heme synthesis decreases, and iron can accumulate in tissues, where it can eventually lead to organ damage. Zinc. The trace mineral zinc functions as a co-enzyme that facilitates the synthesis of the heme portion of hemoglobin. B vitamins. The B vitamins folate and vitamin B12 function as co-enzymes that facilitate DNA synthesis. Thus, both are critical for the synthesis of new cells, including erythrocytes.

Stethoscope Placement for Auscultation

Proper placement of the bell of the stethoscope facilitates auscultation. At each of the four locations on the chest, a different valve can be heard.

Which component of the heart conduction system would have the slowest rate of firing?

Purkinje fibers

Maintenance of Homeostasis

Recall that body temperature is regulated via a classic negative-feedback loop. If you were exercising on a warm day, your rising core body temperature would trigger several homeostatic mechanisms, including increased transport of blood from your core to your body periphery, which is typically cooler. As blood passes through the vessels of the skin, heat would be dissipated to the environment, and the blood returning to your body core would be cooler. In contrast, on a cold day, blood is diverted away from the skin to maintain a warmer body core. In extreme cases, this may result in frostbite. Blood also helps to maintain the chemical balance of the body. Proteins and other compounds in blood act as buffers, which thereby help to regulate the pH of body tissues. Blood also helps to regulate the water content of body cells.

Internal Structure of the Heart

Recall that the heart's contraction cycle follows a dual pattern of circulation—the pulmonary and systemic circuits—because of the pairs of chambers that pump blood into the circulation. In order to develop a more precise understanding of cardiac function, it is first necessary to explore the internal anatomical structures in more detail.

Left Ventricle

Recall that, although both sides of the heart will pump the same amount of blood, the muscular layer is much thicker in the left ventricle compared to the right (see Figure). Like the right ventricle, the left also has trabeculae carneae, but there is no moderator band. The mitral valve is connected to papillary muscles via chordae tendineae. There are two papillary muscles on the left—the anterior and posterior—as opposed to three on the right. The left ventricle is the major pumping chamber for the systemic circuit; it ejects blood into the aorta through the aortic semilunar valve.

thrombocytes

platelets, one of the formed elements of blood that consists of cell fragments broken off from megakaryocytes

A patient has been suffering for 2 months with a chronic, watery diarrhea. A blood test is likely to reveal ________.

polycythemia

ejection fraction

portion of the blood that is pumped or ejected from the heart with each contraction; mathematically represented by SV divided by EDV

A young woman has been experiencing unusually heavy menstrual bleeding for several years. She follows a strict vegan diet (no animal foods). She is at risk for what disorder, and why?

She is at risk for anemia, because her unusually heavy menstrual bleeding results in excessive loss of erythrocytes each month. At the same time, her vegan diet means that she does not have dietary sources of heme iron. The non-heme iron she consumes in plant foods is not as well absorbed as heme iron.

truncus arteriosus

portion of the primitive heart that will eventually divide and give rise to the ascending aorta and pulmonary trunk

Watch this video to see doctors discuss the dangers of blood doping in sports. What are the some potential side effects of blood doping?

Side effects can include heart disease, stroke, pulmonary embolism, and virus transmission.

primitive atrium

portion of the primitive heart tube that eventually becomes the anterior portions of both the right and left atria, and the two auricles

primitive ventricle

portion of the primitive heart tube that eventually forms the left ventricle

Bone Marrow Sampling and Transplants

Sometimes, a healthcare provider will order a bone marrow biopsy, a diagnostic test of a sample of red bone marrow, or a bone marrow transplant, a treatment in which a donor's healthy bone marrow—and its stem cells—replaces the faulty bone marrow of a patient. These tests and procedures are often used to assist in the diagnosis and treatment of various severe forms of anemia, such as thalassemia major and sickle cell anemia, as well as some types of cancer, specifically leukemia. In the past, when a bone marrow sample or transplant was necessary, the procedure would have required inserting a large-bore needle into the region near the iliac crest of the pelvic bones (os coxae). This location was preferred, since its location close to the body surface makes it more accessible, and it is relatively isolated from most vital organs. Unfortunately, the procedure is quite painful. Now, direct sampling of bone marrow can often be avoided. In many cases, stem cells can be isolated in just a few hours from a sample of a patient's blood. The isolated stem cells are then grown in culture using the appropriate hemopoietic growth factors, and analyzed or sometimes frozen for later use. For an individual requiring a transplant, a matching donor is essential to prevent the immune system from destroying the donor cells—a phenomenon known as tissue rejection. To treat patients with bone marrow transplants, it is first necessary to destroy the patient's own diseased marrow through radiation and/or chemotherapy. Donor bone marrow stem cells are then intravenously infused. From the bloodstream, they establish themselves in the recipient's bone marrow.

Conduction System of the Heart

Specialized conducting components of the heart include the sinoatrial node, the internodal pathways, the atrioventricular node, the atrioventricular bundle, the right and left bundle branches, and the Purkinje fibers.

bulbus cordis

portion of the primitive heart tube that will eventually develop into the right ventricle

Rh Blood Groups

The Rh blood group is classified according to the presence or absence of a second erythrocyte antigen identified as Rh. (It was first discovered in a type of primate known as a rhesus macaque, which is often used in research, because its blood is similar to that of humans.) Although dozens of Rh antigens have been identified, only one, designated D, is clinically important. Those who have the Rh D antigen present on their erythrocytes—about 85 percent of Americans—are described as Rh positive (Rh+) and those who lack it are Rh negative (Rh−). Note that the Rh group is distinct from the ABO group, so any individual, no matter their ABO blood type, may have or lack this Rh antigen. When identifying a patient's blood type, the Rh group is designated by adding the word positive or negative to the ABO type. For example, A positive (A+) means ABO group A blood with the Rh antigen present, and AB negative (AB−) means ABO group AB blood without the Rh antigen. Table summarizes the distribution of the ABO and Rh blood types within the United States.

Would you expect a patient with a form of cancer called acute myelogenous leukemia to experience impaired production of erythrocytes, or impaired production of lymphocytes? Explain your choice

The adjective myelogenous suggests a condition originating from (generated by) myeloid cells. Acute myelogenous leukemia impairs the production of erythrocytes and other mature formed elements of the myeloid stem cell lineage. Lymphocytes arise from the lymphoid stem cell line.

Coronary Circulation

The anterior view of the heart shows the prominent coronary surface vessels. The posterior view of the heart shows the prominent coronary surface vessels.

When the ventricles begin to contract, pressure within the ventricles rises and blood flows toward the area of lowest pressure, which is initially in the atria. This backflow causes the cusps of the tricuspid and mitral (bicuspid) valves to close. These valves are tied down to the papillary muscles by chordae tendineae. During the relaxation phase of the cardiac cycle, the papillary muscles are also relaxed and the tension on the chordae tendineae is slight (see Figureb). However, as the myocardium of the ventricle contracts, so do the papillary muscles. This creates tension on the chordae tendineae (see Figureb), helping to hold the cusps of the atrioventricular valves in place and preventing them from being blown back into the atria.

The aortic and pulmonary semilunar valves lack the chordae tendineae and papillary muscles associated with the atrioventricular valves. Instead, they consist of pocket-like folds of endocardium reinforced with additional connective tissue. When the ventricles relax and the change in pressure forces the blood toward the ventricles, the blood presses against these cusps and seals the openings.

The force the heart must overcome to pump blood is known as ________.

afterload

Atrioventricular (AV) Node

The atrioventricular (AV) node is a second clump of specialized myocardial conductive cells, located in the inferior portion of the right atrium within the atrioventricular septum. The septum prevents the impulse from spreading directly to the ventricles without passing through the AV node. There is a critical pause before the AV node depolarizes and transmits the impulse to the atrioventricular bundle (see Figure, step 3). This delay in transmission is partially attributable to the small diameter of the cells of the node, which slow the impulse. Also, conduction between nodal cells is less efficient than between conducting cells. These factors mean that it takes the impulse approximately 100 ms to pass through the node. This pause is critical to heart function, as it allows the atrial cardiomyocytes to complete their contraction that pumps blood into the ventricles before the impulse is transmitted to the cells of the ventricle itself. With extreme stimulation by the SA node, the AV node can transmit impulses maximally at 220 per minute. This establishes the typical maximum heart rate in a healthy young individual. Damaged hearts or those stimulated by drugs can contract at higher rates, but at these rates, the heart can no longer effectively pump blood.

Overview of the Cardiac Cycle

The cardiac cycle begins with atrial systole and progresses to ventricular systole, atrial diastole, and ventricular diastole, when the cycle begins again. Correlations to the ECG are highlighted.

Describe one cardiac cycle, beginning with both atria and ventricles relaxed.

The cardiac cycle comprises a complete relaxation and contraction of both the atria and ventricles, and lasts approximately 0.8 seconds. Beginning with all chambers in diastole, blood flows passively from the veins into the atria and past the atrioventricular valves into the ventricles. The atria begin to contract following depolarization of the atria and pump blood into the ventricles. The ventricles begin to contract, raising pressure within the ventricles. When ventricular pressure rises above the pressure in the two major arteries, blood pushes open the two semilunar valves and moves into the pulmonary trunk and aorta in the ventricular ejection phase. Following ventricular repolarization, the ventricles begin to relax, and pressure within the ventricles drops. When the pressure falls below that of the atria, blood moves from the atria into the ventricles, opening the atrioventricular valves and marking one complete heart cycle.

Input to the Cardiovascular Center

The cardiovascular center receives input from a series of visceral receptors with impulses traveling through visceral sensory fibers within the vagus and sympathetic nerves via the cardiac plexus. Among these receptors are various proprioreceptors, baroreceptors, and chemoreceptors, plus stimuli from the limbic system. Collectively, these inputs normally enable the cardiovascular centers to regulate heart function precisely, a process known as cardiac reflexes. Increased physical activity results in increased rates of firing by various proprioreceptors located in muscles, joint capsules, and tendons. Any such increase in physical activity would logically warrant increased blood flow. The cardiac centers monitor these increased rates of firing, and suppress parasympathetic stimulation and increase sympathetic stimulation as needed in order to increase blood flow. Similarly, baroreceptors are stretch receptors located in the aortic sinus, carotid bodies, the venae cavae, and other locations, including pulmonary vessels and the right side of the heart itself. Rates of firing from the baroreceptors represent blood pressure, level of physical activity, and the relative distribution of blood. The cardiac centers monitor baroreceptor firing to maintain cardiac homeostasis, a mechanism called the baroreceptor reflex. With increased pressure and stretch, the rate of baroreceptor firing increases, and the cardiac centers decrease sympathetic stimulation and increase parasympathetic stimulation. As pressure and stretch decrease, the rate of baroreceptor firing decreases, and the cardiac centers increase sympathetic stimulation and decrease parasympathetic stimulation. There is a similar reflex, called the atrial reflex or Bainbridge reflex, associated with varying rates of blood flow to the atria. Increased venous return stretches the walls of the atria where specialized baroreceptors are located. However, as the atrial baroreceptors increase their rate of firing and as they stretch due to the increased blood pressure, the cardiac center responds by increasing sympathetic stimulation and inhibiting parasympathetic stimulation to increase HR. The opposite is also true. Increased metabolic byproducts associated with increased activity, such as carbon dioxide, hydrogen ions, and lactic acid, plus falling oxygen levels, are detected by a suite of chemoreceptors innervated by the glossopharyngeal and vagus nerves. These chemoreceptors provide feedback to the cardiovascular centers about the need for increased or decreased blood flow, based on the relative levels of these substances. The limbic system can also significantly impact HR related to emotional state. During periods of stress, it is not unusual to identify higher than normal HRs, often accompanied by a surge in the stress hormone cortisol. Individuals experiencing extreme anxiety may manifest panic attacks with symptoms that resemble those of heart attacks. These events are typically transient and treatable. Meditation techniques have been developed to ease anxiety and have been shown to lower HR effectively. Doing simple deep and slow breathing exercises with one's eyes closed can also significantly reduce this anxiety and HR.

Epinephrine and Norepinephrine

The catecholamines, epinephrine and NE, secreted by the adrenal medulla form one component of the extended fight-or-flight mechanism. The other component is sympathetic stimulation. Epinephrine and NE have similar effects: binding to the beta-1 receptors, and opening sodium and calcium ion chemical- or ligand-gated channels. The rate of depolarization is increased by this additional influx of positively charged ions, so the threshold is reached more quickly and the period of repolarization is shortened. However, massive releases of these hormones coupled with sympathetic stimulation may actually lead to arrhythmias. There is no parasympathetic stimulation to the adrenal medulla.

The process in which antibodies attach to antigens, causing the formation of masses of linked cells, is called ________.

agglutination

thrombus

aggregation of fibrin, platelets, and erythrocytes in an intact artery or vein

Recall that blood is a connective tissue. Like all connective tissues, it is made up of cellular elements and an extracellular matrix. The cellular elements—referred to as the formed elements—include red blood cells (RBCs), white blood cells (WBCs), and cell fragments called platelets.

The extracellular matrix, called plasma, makes blood unique among connective tissues because it is fluid. This fluid, which is mostly water, perpetually suspends the formed elements and enables them to circulate throughout the body within the cardiovascular system.

lymphocytes

agranular leukocytes of the lymphoid stem cell line, many of which function in specific immunity

Why would it be incorrect to refer to the formed elements as cells?

The formed elements include erythrocytes and leukocytes, which are cells (although mature erythrocytes do not have a nucleus); however, the formed elements also include platelets, which are not true cells but cell fragments.

Eosinophils typically represent 2-4 percent of total leukocyte count. They are also 10-12 µm in diameter. The granules of eosinophils stain best with an acidic stain known as eosin. The nucleus of the eosinophil will typically have two to three lobes and, if stained properly, the granules will have a distinct red to orange color.

The granules of eosinophils include antihistamine molecules, which counteract the activities of histamines, inflammatory chemicals produced by basophils and mast cells. Some eosinophil granules contain molecules toxic to parasitic worms, which can enter the body through the integument, or when an individual consumes raw or undercooked fish or meat. Eosinophils are also capable of phagocytosis and are particularly effective when antibodies bind to the target and form an antigen-antibody complex. High counts of eosinophils are typical of patients experiencing allergies, parasitic worm infestations, and some autoimmune diseases. Low counts may be due to drug toxicity and stress.

Why is it so important for the human heart to develop early and begin functioning within the developing embryo?

The human embryo is rapidly growing and has great demands for nutrients and oxygen, while producing waste products including carbon dioxide. All of these materials must be received from or delivered to the mother for processing. Without an efficient early circulatory system, this would be impossible.

Chambers and Circulation through the Heart

The human heart consists of four chambers: The left side and the right side each have one atrium and one ventricle. Each of the upper chambers, the right atrium (plural = atria) and the left atrium, acts as a receiving chamber and contracts to push blood into the lower chambers, the right ventricle and the left ventricle. The ventricles serve as the primary pumping chambers of the heart, propelling blood to the lungs or to the rest of the body. There are two distinct but linked circuits in the human circulation called the pulmonary and systemic circuits. Although both circuits transport blood and everything it carries, we can initially view the circuits from the point of view of gases. The pulmonary circuit transports blood to and from the lungs, where it picks up oxygen and delivers carbon dioxide for exhalation. The systemic circuit transports oxygenated blood to virtually all of the tissues of the body and returns relatively deoxygenated blood and carbon dioxide to the heart to be sent back to the pulmonary circulation. The right ventricle pumps deoxygenated blood into the pulmonary trunk, which leads toward the lungs and bifurcates into the left and right pulmonary arteries. These vessels in turn branch many times before reaching the pulmonary capillaries, where gas exchange occurs: Carbon dioxide exits the blood and oxygen enters. The pulmonary trunk arteries and their branches are the only arteries in the post-natal body that carry relatively deoxygenated blood. Highly oxygenated blood returning from the pulmonary capillaries in the lungs passes through a series of vessels that join together to form the pulmonary veins—the only post-natal veins in the body that carry highly oxygenated blood. The pulmonary veins conduct blood into the left atrium, which pumps the blood into the left ventricle, which in turn pumps oxygenated blood into the aorta and on to the many branches of the systemic circuit. Eventually, these vessels will lead to the systemic capillaries, where exchange with the tissue fluid and cells of the body occurs. In this case, oxygen and nutrients exit the systemic capillaries to be used by the cells in their metabolic processes, and carbon dioxide and waste products will enter the blood. The blood exiting the systemic capillaries is lower in oxygen concentration than when it entered. The capillaries will ultimately unite to form venules, joining to form ever-larger veins, eventually flowing into the two major systemic veins, the superior vena cava and the inferior vena cava, which return blood to the right atrium. The blood in the superior and inferior venae cavae flows into the right atrium, which pumps blood into the right ventricle. This process of blood circulation continues as long as the individual remains alive. Understanding the flow of blood through the pulmonary and systemic circuits is critical to all health professions (Figure).

Location of the Heart

The human heart is located within the thoracic cavity, medially between the lungs in the space known as the mediastinum. Figure shows the position of the heart within the thoracic cavity. Within the mediastinum, the heart is separated from the other mediastinal structures by a tough membrane known as the pericardium, or pericardial sac, and sits in its own space called the pericardial cavity. The dorsal surface of the heart lies near the bodies of the vertebrae, and its anterior surface sits deep to the sternum and costal cartilages. The great veins, the superior and inferior venae cavae, and the great arteries, the aorta and pulmonary trunk, are attached to the superior surface of the heart, called the base. The base of the heart is located at the level of the third costal cartilage, as seen in Figure. The inferior tip of the heart, the apex, lies just to the left of the sternum between the junction of the fourth and fifth ribs near their articulation with the costal cartilages. The right side of the heart is deflected anteriorly, and the left side is deflected posteriorly. It is important to remember the position and orientation of the heart when placing a stethoscope on the chest of a patient and listening for heart sounds, and also when looking at images taken from a midsagittal perspective. The slight deviation of the apex to the left is reflected in a depression in the medial surface of the inferior lobe of the left lung, called the cardiac notch.

Development of the Heart

The human heart is the first functional organ to develop. It begins beating and pumping blood around day 21 or 22, a mere three weeks after fertilization. This emphasizes the critical nature of the heart in distributing blood through the vessels and the vital exchange of nutrients, oxygen, and wastes both to and from the developing baby. The critical early development of the heart is reflected by the prominent heart bulge that appears on the anterior surface of the embryo. The heart forms from an embryonic tissue called mesoderm around 18 to 19 days after fertilization. Mesoderm is one of the three primary germ layers that differentiates early in development that collectively gives rise to all subsequent tissues and organs. The heart begins to develop near the head of the embryo in a region known as the cardiogenic area. Following chemical signals called factors from the underlying endoderm (another of the three primary germ layers), the cardiogenic area begins to form two strands called the cardiogenic cords (Figure). As the cardiogenic cords develop, a lumen rapidly develops within them. At this point, they are referred to as endocardial tubes. The two tubes migrate together and fuse to form a single primitive heart tube. The primitive heart tube quickly forms five distinct regions. From head to tail, these include the truncus arteriosus, bulbus cordis, primitive ventricle, primitive atrium, and the sinus venosus. Initially, all venous blood flows into the sinus venosus, and contractions propel the blood from tail to head, or from the sinus venosus to the truncus arteriosus. This is a very different pattern from that of an adult.

Intrinsic Pathway

The intrinsic pathway (also known as the contact activation pathway) is longer and more complex. In this case, the factors involved are intrinsic to (present within) the bloodstream. The pathway can be prompted by damage to the tissues, resulting from internal factors such as arterial disease; however, it is most often initiated when factor XII (Hageman factor) comes into contact with foreign materials, such as when a blood sample is put into a glass test tube. Within the body, factor XII is typically activated when it encounters negatively charged molecules, such as inorganic polymers and phosphate produced earlier in the series of intrinsic pathway reactions. Factor XII sets off a series of reactions that in turn activates factor XI (antihemolytic factor C or plasma thromboplastin antecedent) then factor IX (antihemolytic factor B or plasma thromboplasmin). In the meantime, chemicals released by the platelets increase the rate of these activation reactions. Finally, factor VIII (antihemolytic factor A) from the platelets and endothelial cells combines with factor IX (antihemolytic factor B or plasma thromboplasmin) to form an enzyme complex that activates factor X (Stuart-Prower factor or thrombokinase), leading to the common pathway. The events in the intrinsic pathway are completed in a few minutes.

monocytes

agranular leukocytes of the myeloid stem cell line that circulate in the bloodstream; tissue monocytes are macrophages

In the lungs, hemoglobin picks up oxygen, which binds to the iron ions, forming oxyhemoglobin. The bright red, oxygenated hemoglobin travels to the body tissues, where it releases some of the oxygen molecules, becoming darker red deoxyhemoglobin, sometimes referred to as reduced hemoglobin. Oxygen release depends on the need for oxygen in the surrounding tissues, so hemoglobin rarely if ever leaves all of its oxygen behind. In the capillaries, carbon dioxide enters the bloodstream. About 76 percent dissolves in the plasma, some of it remaining as dissolved CO2, and the remainder forming bicarbonate ion. About 23-24 percent of it binds to the amino acids in hemoglobin, forming a molecule known as carbaminohemoglobin. From the capillaries, the hemoglobin carries carbon dioxide back to the lungs, where it releases it for exchange of oxygen. Changes in the levels of RBCs can have significant effects on the body's ability to effectively deliver oxygen to the tissues. Ineffective hematopoiesis results in insufficient numbers of RBCs and results in one of several forms of anemia. An overproduction of RBCs produces a condition called polycythemia. The primary drawback with polycythemia is not a failure to directly deliver enough oxygen to the tissues, but rather the increased viscosity of the blood, which makes it more difficult for the heart to circulate the blood. In patients with insufficient hemoglobin, the tissues may not receive sufficient oxygen, resulting in another form of anemia. In determining oxygenation of tissues, the value of greatest interest in healthcare is the percent saturation; that is, the percentage of hemoglobin sites occupied by oxygen in a patient's blood. Clinically this value is commonly referred to simply as "percent sat." Percent saturation is normally monitored using a device known as a pulse oximeter, which is applied to a thin part of the body, typically the tip of the patient's finger. The device works by sending two different wavelengths of light (one red, the other infrared) through the finger and measuring the light with a photodetector as it exits. Hemoglobin absorbs light differentially depending upon its saturation with oxygen. The machine calibrates the amount of light received by the photodetector against the amount absorbed by the partially oxygenated hemoglobin and presents the data as percent saturation. Normal pulse oximeter readings range from 95-100 percent. Lower percentages reflect hypoxemia, or low blood oxygen. The term hypoxia is more generic and simply refers to low oxygen levels. Oxygen levels are also directly monitored from free oxygen in the plasma typically following an arterial stick. When this method is applied, the amount of oxygen present is expressed in terms of partial pressure of oxygen or simply pO2 and is typically recorded in units of millimeters of mercury, mm Hg.

The kidneys filter about 180 liters (~380 pints) of blood in an average adult each day, or about 20 percent of the total resting volume, and thus serve as ideal sites for receptors that determine oxygen saturation. In response to hypoxemia, less oxygen will exit the vessels supplying the kidney, resulting in hypoxia (low oxygen concentration) in the tissue fluid of the kidney where oxygen concentration is actually monitored. Interstitial fibroblasts within the kidney secrete EPO, thereby increasing erythrocyte production and restoring oxygen levels. In a classic negative-feedback loop, as oxygen saturation rises, EPO secretion falls, and vice versa, thereby maintaining homeostasis. Populations dwelling at high elevations, with inherently lower levels of oxygen in the atmosphere, naturally maintain a hematocrit higher than people living at sea level. Consequently, people traveling to high elevations may experience symptoms of hypoxemia, such as fatigue, headache, and shortness of breath, for a few days after their arrival. In response to the hypoxemia, the kidneys secrete EPO to step up the production of erythrocytes until homeostasis is achieved once again. To avoid the symptoms of hypoxemia, or altitude sickness, mountain climbers typically rest for several days to a week or more at a series of camps situated at increasing elevations to allow EPO levels and, consequently, erythrocyte counts to rise. When climbing the tallest peaks, such as Mt. Everest and K2 in the Himalayas, many mountain climbers rely upon bottled oxygen as they near the summit.

In preparation for a scheduled surgery, a patient visits the hospital lab for a blood draw. The technician collects a blood sample and performs a test to determine its type. She places a sample of the patient's blood in two wells. To the first well she adds anti-A antibody. To the second she adds anti-B antibody. Both samples visibly agglutinate. Has the technician made an error, or is this a normal response? If normal, what blood type does this indicate?

The lab technician has not made an error. Blood type AB has both A and B surface antigens, and neither anti-A nor anti-B antibodies circulating in the plasma. When anti-A antibodies (added to the first well) contact A antigens on AB erythrocytes, they will cause agglutination. Similarly, when anti-B antibodies contact B antigens on AB erythrocytes, they will cause agglutination.

Membranes

The membrane that directly surrounds the heart and defines the pericardial cavity is called the pericardium or pericardial sac. It also surrounds the "roots" of the major vessels, or the areas of closest proximity to the heart. The pericardium, which literally translates as "around the heart," consists of two distinct sublayers: the sturdy outer fibrous pericardium and the inner serous pericardium. The fibrous pericardium is made of tough, dense connective tissue that protects the heart and maintains its position in the thorax. The more delicate serous pericardium consists of two layers: the parietal pericardium, which is fused to the fibrous pericardium, and an inner visceral pericardium, or epicardium, which is fused to the heart and is part of the heart wall. The pericardial cavity, filled with lubricating serous fluid, lies between the epicardium and the pericardium. In most organs within the body, visceral serous membranes such as the epicardium are microscopic. However, in the case of the heart, it is not a microscopic layer but rather a macroscopic layer, consisting of a simple squamous epithelium called a mesothelium, reinforced with loose, irregular, or areolar connective tissue that attaches to the pericardium. This mesothelium secretes the lubricating serous fluid that fills the pericardial cavity and reduces friction as the heart contracts. Figure illustrates the pericardial membrane and the layers of the heart.

Differences in Ventricular Muscle Thickness

The myocardium in the left ventricle is significantly thicker than that of the right ventricle. Both ventricles pump the same amount of blood, but the left ventricle must generate a much greater pressure to overcome greater resistance in the systemic circuit. The ventricles are shown in both relaxed and contracting states. Note the differences in the relative size of the lumens, the region inside each ventricle where the blood is contained.

A patient's hematocrit is 42 percent. Approximately what percentage of the patient's blood is plasma?

The patient's blood is approximately 58 percent plasma (since the buffy coat is less than 1 percent).

Comparative Rates of Conduction System Firing

The pattern of prepotential or spontaneous depolarization, followed by rapid depolarization and repolarization just described, are seen in the SA node and a few other conductive cells in the heart. Since the SA node is the pacemaker, it reaches threshold faster than any other component of the conduction system. It will initiate the impulses spreading to the other conducting cells. The SA node, without nervous or endocrine control, would initiate a heart impulse approximately 80-100 times per minute. Although each component of the conduction system is capable of generating its own impulse, the rate progressively slows as you proceed from the SA node to the Purkinje fibers. Without the SA node, the AV node would generate a heart rate of 40-60 beats per minute. If the AV node were blocked, the atrioventricular bundle would fire at a rate of approximately 30-40 impulses per minute. The bundle branches would have an inherent rate of 20-30 impulses per minute, and the Purkinje fibers would fire at 15-20 impulses per minute. While a few exceptionally trained aerobic athletes demonstrate resting heart rates in the range of 30-40 beats per minute (the lowest recorded figure is 28 beats per minute for Miguel Indurain, a cyclist), for most individuals, rates lower than 50 beats per minute would indicate a condition called bradycardia. Depending upon the specific individual, as rates fall much below this level, the heart would be unable to maintain adequate flow of blood to vital tissues, initially resulting in decreasing loss of function across the systems, unconsciousness, and ultimately death.

Pericardial Membranes and Layers of the Heart Wall

The pericardial membrane that surrounds the heart consists of three layers and the pericardial cavity. The heart wall also consists of three layers. The pericardial membrane and the heart wall share the epicardium.

CPR

The position of the heart in the torso between the vertebrae and sternum (see Figure for the position of the heart within the thorax) allows for individuals to apply an emergency technique known as cardiopulmonary resuscitation (CPR) if the heart of a patient should stop. By applying pressure with the flat portion of one hand on the sternum in the area between the line at T4 and T9 (Figure), it is possible to manually compress the blood within the heart enough to push some of the blood within it into the pulmonary and systemic circuits. This is particularly critical for the brain, as irreversible damage and death of neurons occur within minutes of loss of blood flow. Current standards call for compression of the chest at least 5 cm deep and at a rate of 100 compressions per minute, a rate equal to the beat in "Staying Alive," recorded in 1977 by the Bee Gees. If you are unfamiliar with this song, a version is available on www.youtube.com. At this stage, the emphasis is on performing high-quality chest compressions, rather than providing artificial respiration. CPR is generally performed until the patient regains spontaneous contraction or is declared dead by an experienced healthcare professional. When performed by untrained or overzealous individuals, CPR can result in broken ribs or a broken sternum, and can inflict additional severe damage on the patient. It is also possible, if the hands are placed too low on the sternum, to manually drive the xiphoid process into the liver, a consequence that may prove fatal for the patient. Proper training is essential. This proven life-sustaining technique is so valuable that virtually all medical personnel as well as concerned members of the public should be certified and routinely recertified in its application. CPR courses are offered at a variety of locations, including colleges, hospitals, the American Red Cross, and some commercial companies. They normally include practice of the compression technique on a mannequin.

Action Potential at the SA Node

The prepotential is due to a slow influx of sodium ions until the threshold is reached followed by a rapid depolarization and repolarization. The prepotential accounts for the membrane reaching threshold and initiates the spontaneous depolarization and contraction of the cell. Note the lack of a resting potential.

Visit this site to observe an echocardiogram of actual heart valves opening and closing. Although much of the heart has been "removed" from this gif loop so the chordae tendineae are not visible, why is their presence more critical for the atrioventricular valves (tricuspid and mitral) than the semilunar (aortic and pulmonary) valves?

The pressure gradient between the atria and the ventricles is much greater than that between the ventricles and the pulmonary trunk and aorta. Without the presence of the chordae tendineae and papillary muscles, the valves would be blown back (prolapsed) into the atria and blood would regurgitate.

Summary of Major Factors Influencing Cardiac Output

The primary factors influencing HR include autonomic innervation plus endocrine control. Not shown are environmental factors, such as electrolytes, metabolic products, and temperature. The primary factors controlling SV include preload, contractility, and afterload. Other factors such as electrolytes may be classified as either positive or negative inotropic agents.

Functions of Blood

The primary function of blood is to deliver oxygen and nutrients to and remove wastes from body cells, but that is only the beginning of the story. The specific functions of blood also include defense, distribution of heat, and maintenance of homeostasis.

Why is the pressure in the pulmonary circulation lower than in the systemic circulation?

The pulmonary circuit consists of blood flowing to and from the lungs, whereas the systemic circuit carries blood to and from the entire body. The systemic circuit is far more extensive, consisting of far more vessels and offers much greater resistance to the flow of blood, so the heart must generate a higher pressure to overcome this resistance. This can be seen in the thickness of the myocardium in the ventricles.

Extrinsic Pathway

The quicker responding and more direct extrinsic pathway (also known as the tissue factor pathway) begins when damage occurs to the surrounding tissues, such as in a traumatic injury. Upon contact with blood plasma, the damaged extravascular cells, which are extrinsic to the bloodstream, release factor III (thromboplastin). Sequentially, Ca2+ then factor VII (proconvertin), which is activated by factor III, are added, forming an enzyme complex. This enzyme complex leads to activation of factor X (Stuart-Prower factor), which activates the common pathway discussed below. The events in the extrinsic pathway are completed in a matter of seconds.

Right Atrium

The right atrium serves as the receiving chamber for blood returning to the heart from the systemic circulation. The two major systemic veins, the superior and inferior venae cavae, and the large coronary vein called the coronary sinus that drains the heart myocardium empty into the right atrium. The superior vena cava drains blood from regions superior to the diaphragm: the head, neck, upper limbs, and the thoracic region. It empties into the superior and posterior portions of the right atrium. The inferior vena cava drains blood from areas inferior to the diaphragm: the lower limbs and abdominopelvic region of the body. It, too, empties into the posterior portion of the atria, but inferior to the opening of the superior vena cava. Immediately superior and slightly medial to the opening of the inferior vena cava on the posterior surface of the atrium is the opening of the coronary sinus. This thin-walled vessel drains most of the coronary veins that return systemic blood from the heart. The majority of the internal heart structures discussed in this and subsequent sections are illustrated in Figure. While the bulk of the internal surface of the right atrium is smooth, the depression of the fossa ovalis is medial, and the anterior surface demonstrates prominent ridges of muscle called the pectinate muscles. The right auricle also has pectinate muscles. The left atrium does not have pectinate muscles except in the auricle. The atria receive venous blood on a nearly continuous basis, preventing venous flow from stopping while the ventricles are contracting. While most ventricular filling occurs while the atria are relaxed, they do demonstrate a contractile phase and actively pump blood into the ventricles just prior to ventricular contraction. The opening between the atrium and ventricle is guarded by the tricuspid valve.

Right Ventricle

The right ventricle receives blood from the right atrium through the tricuspid valve. Each flap of the valve is attached to strong strands of connective tissue, the chordae tendineae, literally "tendinous cords," or sometimes more poetically referred to as "heart strings." There are several chordae tendineae associated with each of the flaps. They are composed of approximately 80 percent collagenous fibers with the remainder consisting of elastic fibers and endothelium. They connect each of the flaps to a papillary muscle that extends from the inferior ventricular surface. There are three papillary muscles in the right ventricle, called the anterior, posterior, and septal muscles, which correspond to the three sections of the valves. When the myocardium of the ventricle contracts, pressure within the ventricular chamber rises. Blood, like any fluid, flows from higher pressure to lower pressure areas, in this case, toward the pulmonary trunk and the atrium. To prevent any potential backflow, the papillary muscles also contract, generating tension on the chordae tendineae. This prevents the flaps of the valves from being forced into the atria and regurgitation of the blood back into the atria during ventricular contraction. Figure shows papillary muscles and chordae tendineae attached to the tricuspid valve.

Shape and Size of the Heart

The shape of the heart is similar to a pinecone, rather broad at the superior surface and tapering to the apex (see Figure). A typical heart is approximately the size of your fist: 12 cm (5 in) in length, 8 cm (3.5 in) wide, and 6 cm (2.5 in) in thickness. Given the size difference between most members of the sexes, the weight of a female heart is approximately 250-300 grams (9 to 11 ounces), and the weight of a male heart is approximately 300-350 grams (11 to 12 ounces). The heart of a well-trained athlete, especially one specializing in aerobic sports, can be considerably larger than this. Cardiac muscle responds to exercise in a manner similar to that of skeletal muscle. That is, exercise results in the addition of protein myofilaments that increase the size of the individual cells without increasing their numbers, a concept called hypertrophy. Hearts of athletes can pump blood more effectively at lower rates than those of nonathletes. Enlarged hearts are not always a result of exercise; they can result from pathologies, such as hypertrophic cardiomyopathy. The cause of an abnormally enlarged heart muscle is unknown, but the condition is often undiagnosed and can cause sudden death in apparently otherwise healthy young people.

positive chemotaxis

process in which a cell is attracted to move in the direction of chemical stimuli

Disorders of Erythrocytes

The size, shape, and number of erythrocytes, and the number of hemoglobin molecules can have a major impact on a person's health. When the number of RBCs or hemoglobin is deficient, the general condition is called anemia. There are more than 400 types of anemia and more than 3.5 million Americans suffer from this condition. Anemia can be broken down into three major groups: those caused by blood loss, those caused by faulty or decreased RBC production, and those caused by excessive destruction of RBCs. Clinicians often use two groupings in diagnosis: The kinetic approach focuses on evaluating the production, destruction, and removal of RBCs, whereas the morphological approach examines the RBCs themselves, paying particular emphasis to their size. A common test is the mean corpuscle volume (MCV), which measures size. Normal-sized cells are referred to as normocytic, smaller-than-normal cells are referred to as microcytic, and larger-than-normal cells are referred to as macrocytic. Reticulocyte counts are also important and may reveal inadequate production of RBCs. The effects of the various anemias are widespread, because reduced numbers of RBCs or hemoglobin will result in lower levels of oxygen being delivered to body tissues. Since oxygen is required for tissue functioning, anemia produces fatigue, lethargy, and an increased risk for infection. An oxygen deficit in the brain impairs the ability to think clearly, and may prompt headaches and irritability. Lack of oxygen leaves the patient short of breath, even as the heart and lungs work harder in response to the deficit.

Fibrinolysis

The stabilized clot is acted upon by contractile proteins within the platelets. As these proteins contract, they pull on the fibrin threads, bringing the edges of the clot more tightly together, somewhat as we do when tightening loose shoelaces (see Figurea). This process also wrings out of the clot a small amount of fluid called serum, which is blood plasma without its clotting factors. To restore normal blood flow as the vessel heals, the clot must eventually be removed. Fibrinolysis is the gradual degradation of the clot. Again, there is a fairly complicated series of reactions that involves factor XII and protein-catabolizing enzymes. During this process, the inactive protein plasminogen is converted into the active plasmin, which gradually breaks down the fibrin of the clot. Additionally, bradykinin, a vasodilator, is released, reversing the effects of the serotonin and prostaglandins from the platelets. This allows the smooth muscle in the walls of the vessels to relax and helps to restore the circulation.

Interleukins are associated primarily with which of the following?

all of the above: production of various lymphocytes, immune responses, inflammation

Layers

The wall of the heart is composed of three layers of unequal thickness. From superficial to deep, these are the epicardium, the myocardium, and the endocardium (see Figure). The outermost layer of the wall of the heart is also the innermost layer of the pericardium, the epicardium, or the visceral pericardium discussed earlier. The middle and thickest layer is the myocardium, made largely of cardiac muscle cells. It is built upon a framework of collagenous fibers, plus the blood vessels that supply the myocardium and the nerve fibers that help regulate the heart. It is the contraction of the myocardium that pumps blood through the heart and into the major arteries. The muscle pattern is elegant and complex, as the muscle cells swirl and spiral around the chambers of the heart. They form a figure 8 pattern around the atria and around the bases of the great vessels. Deeper ventricular muscles also form a figure 8 around the two ventricles and proceed toward the apex. More superficial layers of ventricular muscle wrap around both ventricles. This complex swirling pattern allows the heart to pump blood more effectively than a simple linear pattern would. Figure illustrates the arrangement of muscle cells.

Effects of Parasympathetic and Sympathetic Stimulation on Normal Sinus Rhythm

The wave of depolarization in a normal sinus rhythm shows a stable resting HR. Following parasympathetic stimulation, HR slows. Following sympathetic stimulation, HR increases.

Septa of the Heart

The word septum is derived from the Latin for "something that encloses;" in this case, a septum (plural = septa) refers to a wall or partition that divides the heart into chambers. The septa are physical extensions of the myocardium lined with endocardium. Located between the two atria is the interatrial septum. Normally in an adult heart, the interatrial septum bears an oval-shaped depression known as the fossa ovalis, a remnant of an opening in the fetal heart known as the foramen ovale. The foramen ovale allowed blood in the fetal heart to pass directly from the right atrium to the left atrium, allowing some blood to bypass the pulmonary circuit. Within seconds after birth, a flap of tissue known as the septum primum that previously acted as a valve closes the foramen ovale and establishes the typical cardiac circulation pattern. Between the two ventricles is a second septum known as the interventricular septum. Unlike the interatrial septum, the interventricular septum is normally intact after its formation during fetal development. It is substantially thicker than the interatrial septum, since the ventricles generate far greater pressure when they contract. The septum between the atria and ventricles is known as the atrioventricular septum. It is marked by the presence of four openings that allow blood to move from the atria into the ventricles and from the ventricles into the pulmonary trunk and aorta. Located in each of these openings between the atria and ventricles is a valve, a specialized structure that ensures one-way flow of blood. The valves between the atria and ventricles are known generically as atrioventricular valves. The valves at the openings that lead to the pulmonary trunk and aorta are known generically as semilunar valves. The interventricular septum is visible in Figure. In this figure, the atrioventricular septum has been removed to better show the bicupid and tricuspid valves; the interatrial septum is not visible, since its location is covered by the aorta and pulmonary trunk. Since these openings and valves structurally weaken the atrioventricular septum, the remaining tissue is heavily reinforced with dense connective tissue called the cardiac skeleton, or skeleton of the heart. It includes four rings that surround the openings between the atria and ventricles, and the openings to the pulmonary trunk and aorta, and serve as the point of attachment for the heart valves. The cardiac skeleton also provides an important boundary in the heart electrical conduction system.

hemopoiesis

production of the formed elements of blood

Recall that cardiac muscle shares a few characteristics with both skeletal muscle and smooth muscle, but it has some unique properties of its own. Not the least of these exceptional properties is its ability to initiate an electrical potential at a fixed rate that spreads rapidly from cell to cell to trigger the contractile mechanism. This property is known as autorhythmicity. Neither smooth nor skeletal muscle can do this. Even though cardiac muscle has autorhythmicity, heart rate is modulated by the endocrine and nervous systems.

There are two major types of cardiac muscle cells: myocardial contractile cells and myocardial conducting cells. The myocardial contractile cells constitute the bulk (99 percent) of the cells in the atria and ventricles. Contractile cells conduct impulses and are responsible for contractions that pump blood through the body. The myocardial conducting cells (1 percent of the cells) form the conduction system of the heart. Except for Purkinje cells, they are generally much smaller than the contractile cells and have few of the myofibrils or filaments needed for contraction. Their function is similar in many respects to neurons, although they are specialized muscle cells. Myocardial conduction cells initiate and propagate the action potential (the electrical impulse) that travels throughout the heart and triggers the contractions that propel the blood.

Visit this site for a list of normal levels established for many of the substances found in a sample of blood. Serum, one of the specimen types included, refers to a sample of plasma after clotting factors have been removed. What types of measurements are given for levels of glucose in the blood?

There are values given for percent saturation, tension, and blood gas, and there are listings for different types of hemoglobin.

Membrane Potentials and Ion Movement in Cardiac Contractile Cells

There is a distinctly different electrical pattern involving the contractile cells. In this case, there is a rapid depolarization, followed by a plateau phase and then repolarization. This phenomenon accounts for the long refractory periods required for the cardiac muscle cells to pump blood effectively before they are capable of firing for a second time. These cardiac myocytes normally do not initiate their own electrical potential but rather wait for an impulse to reach them. Contractile cells demonstrate a much more stable resting phase than conductive cells at approximately −80 mV for cells in the atria and −90 mV for cells in the ventricles. Despite this initial difference, the other components of their action potentials are virtually identical. In both cases, when stimulated by an action potential, voltage-gated channels rapidly open, beginning the positive-feedback mechanism of depolarization. This rapid influx of positively charged ions raises the membrane potential to approximately +30 mV, at which point the sodium channels close. The rapid depolarization period typically lasts 3-5 ms. Depolarization is followed by the plateau phase, in which membrane potential declines relatively slowly. This is due in large part to the opening of the slow Ca2+ channels, allowing Ca2+ to enter the cell while few K+ channels are open, allowing K+ to exit the cell. The relatively long plateau phase lasts approximately 175 ms. Once the membrane potential reaches approximately zero, the Ca2+ channels close and K+ channels open, allowing K+ to exit the cell. The repolarization lasts approximately 75 ms. At this point, membrane potential drops until it reaches resting levels once more and the cycle repeats. The entire event lasts between 250 and 300 ms (Figure). The absolute refractory period for cardiac contractile muscle lasts approximately 200 ms, and the relative refractory period lasts approximately 50 ms, for a total of 250 ms. This extended period is critical, since the heart muscle must contract to pump blood effectively and the contraction must follow the electrical events. Without extended refractory periods, premature contractions would occur in the heart and would not be compatible with life.

Which of the following statements about mature, circulating erythrocytes is true?

They have no nucleus.

Internal Structures of the Heart

This anterior view of the heart shows the four chambers, the major vessels and their early branches, as well as the valves. The presence of the pulmonary trunk and aorta covers the interatrial septum, and the atrioventricular septum is cut away to show the atrioventricular valves.

cardiac output (CO)

amount of blood pumped by each ventricle during one minute; equals HR multiplied by SV

stroke volume (SV)

amount of blood pumped by each ventricle per contraction; also, the difference between EDV and ESV

ECG Tracing Correlated to the Cardiac Cycle

This diagram correlates an ECG tracing with the electrical and mechanical events of a heart contraction. Each segment of an ECG tracing corresponds to one event in the cardiac cycle.

Development of the Human Heart

This diagram outlines the embryological development of the human heart during the first eight weeks and the subsequent formation of the four heart chambers.

end systolic volume (ESV)

amount of blood remaining in each ventricle following systole

The lifespan of the formed elements is very brief. Although one type of leukocyte called memory cells can survive for years, most erythrocytes, leukocytes, and platelets normally live only a few hours to a few weeks. Thus, the body must form new blood cells and platelets quickly and continuously. When you donate a unit of blood during a blood drive (approximately 475 mL, or about 1 pint), your body typically replaces the donated plasma within 24 hours, but it takes about 4 to 6 weeks to replace the blood cells.

This restricts the frequency with which donors can contribute their blood. The process by which this replacement occurs is called hemopoiesis, or hematopoiesis (from the Greek root haima- = "blood"; -poiesis = "production").

ou will need to do this is a systematic manner, scanning along the image. The standard method is to use a grid, but this is not possible with this resource. Try constructing a simple table with each leukocyte type and then making a mark for each cell type you identify. Attempt to classify at least 50 and perhaps as many as 100 different cells. Based on the percentage of cells that you count, do the numbers represent a normal blood smear or does something appear to be abnormal?

This should appear to be a normal blood smear.

Coagulation

Those more sophisticated and more durable repairs are collectively called coagulation, the formation of a blood clot. The process is sometimes characterized as a cascade, because one event prompts the next as in a multi-level waterfall. The result is the production of a gelatinous but robust clot made up of a mesh of fibrin—an insoluble filamentous protein derived from fibrinogen, the plasma protein introduced earlier—in which platelets and blood cells are trapped. Figure summarizes the three steps of hemostasis.

Hemolytic disease of the newborn is a risk during a subsequent pregnancy in which ________.

an Rh− mother is carrying a second Rh+ fetus

Disorders of Platelets

Thrombocytosis is a condition in which there are too many platelets. This may trigger formation of unwanted blood clots (thrombosis), a potentially fatal disorder. If there is an insufficient number of platelets, called thrombocytopenia, blood may not clot properly, and excessive bleeding may result.

ABO Transfusion Protocols

To avoid transfusion reactions, it is best to transfuse only matching blood types; that is, a type B+ recipient should ideally receive blood only from a type B+ donor and so on. That said, in emergency situations, when acute hemorrhage threatens the patient's life, there may not be time for cross matching to identify blood type. In these cases, blood from a universal donor—an individual with type O− blood—may be transfused. Recall that type O erythrocytes do not display A or B antigens. Thus, anti-A or anti-B antibodies that might be circulating in the patient's blood plasma will not encounter any erythrocyte surface antigens on the donated blood and therefore will not be provoked into a response. One problem with this designation of universal donor is if the O− individual had prior exposure to Rh antigen, Rh antibodies may be present in the donated blood. Also, introducing type O blood into an individual with type A, B, or AB blood will nevertheless introduce antibodies against both A and B antigens, as these are always circulating in the type O blood plasma. This may cause problems for the recipient, but because the volume of blood transfused is much lower than the volume of the patient's own blood, the adverse effects of the relatively few infused plasma antibodies are typically limited. Rh factor also plays a role. If Rh− individuals receiving blood have had prior exposure to Rh antigen, antibodies for this antigen may be present in the blood and trigger agglutination to some degree. Although it is always preferable to cross match a patient's blood before transfusing, in a true life-threatening emergency situation, this is not always possible, and these procedures may be implemented. A patient with blood type AB+ is known as the universal recipient. This patient can theoretically receive any type of blood, because the patient's own blood—having both A and B antigens on the erythrocyte surface—does not produce anti-A or anti-B antibodies. In addition, an Rh+ patient can receive both Rh+ and Rh− blood. However, keep in mind that the donor's blood will contain circulating antibodies, again with possible negative implications. Figure summarizes the blood types and compatibilities. At the scene of multiple-vehicle accidents, military engagements, and natural or human-caused disasters, many victims may suffer simultaneously from acute hemorrhage, yet type O blood may not be immediately available. In these circumstances, medics may at least try to replace some of the volume of blood that has been lost. This is done by intravenous administration of a saline solution that provides fluids and electrolytes in proportions equivalent to those of normal blood plasma. Research is ongoing to develop a safe and effective artificial blood that would carry out the oxygen-carrying function of blood without the RBCs, enabling transfusions in the field without concern for incompatibility. These blood substitutes normally contain hemoglobin- as well as perfluorocarbon-based oxygen carriers.

moderator band

band of myocardium covered by endocardium that arises from the inferior portion of the interventricular septum in the right ventricle and crosses to the anterior papillary muscle; contains conductile fibers that carry electrical signals followed by contraction of the heart

A patient has been experiencing severe, persistent allergy symptoms that are reduced when she takes an antihistamine. Before the treatment, this patient was likely to have had increased activity of which leukocyte?

basophils

Other Factors Influencing Heart Rate

Using a combination of autorhythmicity and innervation, the cardiovascular center is able to provide relatively precise control over HR. However, there are a number of other factors that have an impact on HR as well, including epinephrine, NE, and thyroid hormones; levels of various ions including calcium, potassium, and sodium; body temperature; hypoxia; and pH balance (Table and Table). After reading this section, the importance of maintaining homeostasis should become even more apparent.

Ventricular Diastole

Ventricular relaxation, or diastole, follows repolarization of the ventricles and is represented by the T wave of the ECG. It too is divided into two distinct phases and lasts approximately 430 ms. During the early phase of ventricular diastole, as the ventricular muscle relaxes, pressure on the remaining blood within the ventricle begins to fall. When pressure within the ventricles drops below pressure in both the pulmonary trunk and aorta, blood flows back toward the heart, producing the dicrotic notch (small dip) seen in blood pressure tracings. The semilunar valves close to prevent backflow into the heart. Since the atrioventricular valves remain closed at this point, there is no change in the volume of blood in the ventricle, so the early phase of ventricular diastole is called the isovolumic ventricular relaxation phase, also called isovolumetric ventricular relaxation phase (see Figure). In the second phase of ventricular diastole, called late ventricular diastole, as the ventricular muscle relaxes, pressure on the blood within the ventricles drops even further. Eventually, it drops below the pressure in the atria. When this occurs, blood flows from the atria into the ventricles, pushing open the tricuspid and mitral valves. As pressure drops within the ventricles, blood flows from the major veins into the relaxed atria and from there into the ventricles. Both chambers are in diastole, the atrioventricular valves are open, and the semilunar valves remain closed (see Figure). The cardiac cycle is complete.

Ventricular Systole

Ventricular systole (see Figure) follows the depolarization of the ventricles and is represented by the QRS complex in the ECG. It may be conveniently divided into two phases, lasting a total of 270 ms. At the end of atrial systole and just prior to atrial contraction, the ventricles contain approximately 130 mL blood in a resting adult in a standing position. This volume is known as the end diastolic volume (EDV) or preload. Initially, as the muscles in the ventricle contract, the pressure of the blood within the chamber rises, but it is not yet high enough to open the semilunar (pulmonary and aortic) valves and be ejected from the heart. However, blood pressure quickly rises above that of the atria that are now relaxed and in diastole. This increase in pressure causes blood to flow back toward the atria, closing the tricuspid and mitral valves. Since blood is not being ejected from the ventricles at this early stage, the volume of blood within the chamber remains constant. Consequently, this initial phase of ventricular systole is known as isovolumic contraction, also called isovolumetric contraction (see Figure). In the second phase of ventricular systole, the ventricular ejection phase, the contraction of the ventricular muscle has raised the pressure within the ventricle to the point that it is greater than the pressures in the pulmonary trunk and the aorta. Blood is pumped from the heart, pushing open the pulmonary and aortic semilunar valves. Pressure generated by the left ventricle will be appreciably greater than the pressure generated by the right ventricle, since the existing pressure in the aorta will be so much higher. Nevertheless, both ventricles pump the same amount of blood. This quantity is referred to as stroke volume. Stroke volume will normally be in the range of 70-80 mL. Since ventricular systole began with an EDV of approximately 130 mL of blood, this means that there is still 50-60 mL of blood remaining in the ventricle following contraction. This volume of blood is known as the end systolic volume (ESV).

Granular Leukocytes

We will consider the granular leukocytes in order from most common to least common. All of these are produced in the red bone marrow and have a short lifespan of hours to days. They typically have a lobed nucleus and are classified according to which type of stain best highlights their granules (Figure).

Vascular Spasm

When a vessel is severed or punctured, or when the wall of a vessel is damaged, vascular spasm occurs. In vascular spasm, the smooth muscle in the walls of the vessel contracts dramatically. This smooth muscle has both circular layers; larger vessels also have longitudinal layers. The circular layers tend to constrict the flow of blood, whereas the longitudinal layers, when present, draw the vessel back into the surrounding tissue, often making it more difficult for a surgeon to locate, clamp, and tie off a severed vessel. The vascular spasm response is believed to be triggered by several chemicals called endothelins that are released by vessel-lining cells and by pain receptors in response to vessel injury. This phenomenon typically lasts for up to 30 minutes, although it can last for hours.

A heart block refers to an interruption in the normal conduction pathway. The nomenclature for these is very straightforward. SA nodal blocks occur within the SA node. AV nodal blocks occur within the AV node. Infra-Hisian blocks involve the bundle of His. Bundle branch blocks occur within either the left or right atrioventricular bundle branches. Hemiblocks are partial and occur within one or more fascicles of the atrioventricular bundle branch. Clinically, the most common types are the AV nodal and infra-Hisian blocks. AV blocks are often described by degrees. A first-degree or partial block indicates a delay in conduction between the SA and AV nodes. This can be recognized on the ECG as an abnormally long PR interval. A second-degree or incomplete block occurs when some impulses from the SA node reach the AV node and continue, while others do not. In this instance, the ECG would reveal some P waves not followed by a QRS complex, while others would appear normal. In the third-degree or complete block, there is no correlation between atrial activity (the P wave) and ventricular activity (the QRS complex). Even in the event of a total SA block, the AV node will assume the role of pacemaker and continue initiating contractions at 40-60 contractions per minute, which is adequate to maintain consciousness. Second- and third-degree blocks are demonstrated on the ECG presented in Figure.

When arrhythmias become a chronic problem, the heart maintains a junctional rhythm, which originates in the AV node. In order to speed up the heart rate and restore full sinus rhythm, a cardiologist can implant an artificial pacemaker, which delivers electrical impulses to the heart muscle to ensure that the heart continues to contract and pump blood effectively. These artificial pacemakers are programmable by the cardiologists and can either provide stimulation temporarily upon demand or on a continuous basis. Some devices also contain built-in defibrillators.

A lab technician collects a blood sample in a glass tube. After about an hour, she harvests serum to continue her blood analysis. Explain what has happened during the hour that the sample was in the glass tube.

When blood contacts glass, the intrinsic coagulation pathway is initiated. This leads to the common pathway, and the blood clots. Within about 30 minutes, the clot begins to shrink. After an hour, it is about half its original size. Its heavier weight will cause it to fall to the bottom of the tube during centrifugation, allowing the lab technician to harvest the serum remaining at the top.

Myelofibrosis is a disorder in which inflammation and scar tissue formation in the bone marrow impair hemopoiesis. One sign is an enlarged spleen. Why?

When disease impairs the ability of the bone marrow to participate in hemopoiesis, extramedullary hemopoiesis begins in the patient's liver and spleen. This causes the spleen to enlarge.

Heart Valves

When heart valves do not function properly, they are often described as incompetent and result in valvular heart disease, which can range from benign to lethal. Some of these conditions are congenital, that is, the individual was born with the defect, whereas others may be attributed to disease processes or trauma. Some malfunctions are treated with medications, others require surgery, and still others may be mild enough that the condition is merely monitored since treatment might trigger more serious consequences. Valvular disorders are often caused by carditis, or inflammation of the heart. One common trigger for this inflammation is rheumatic fever, or scarlet fever, an autoimmune response to the presence of a bacterium, Streptococcus pyogenes, normally a disease of childhood. While any of the heart valves may be involved in valve disorders, mitral regurgitation is the most common, detected in approximately 2 percent of the population, and the pulmonary semilunar valve is the least frequently involved. When a valve malfunctions, the flow of blood to a region will often be disrupted. The resulting inadequate flow of blood to this region will be described in general terms as an insufficiency. The specific type of insufficiency is named for the valve involved: aortic insufficiency, mitral insufficiency, tricuspid insufficiency, or pulmonary insufficiency. If one of the cusps of the valve is forced backward by the force of the blood, the condition is referred to as a prolapsed valve. Prolapse may occur if the chordae tendineae are damaged or broken, causing the closure mechanism to fail. The failure of the valve to close properly disrupts the normal one-way flow of blood and results in regurgitation, when the blood flows backward from its normal path. Using a stethoscope, the disruption to the normal flow of blood produces a heart murmur. Stenosis is a condition in which the heart valves become rigid and may calcify over time. The loss of flexibility of the valve interferes with normal function and may cause the heart to work harder to propel blood through the valve, which eventually weakens the heart. Aortic stenosis affects approximately 2 percent of the population over 65 years of age, and the percentage increases to approximately 4 percent in individuals over 85 years. Occasionally, one or more of the chordae tendineae will tear or the papillary muscle itself may die as a component of a myocardial infarction (heart attack). In this case, the patient's condition will deteriorate dramatically and rapidly, and immediate surgical intervention may be required. Auscultation, or listening to a patient's heart sounds, is one of the most useful diagnostic tools, since it is proven, safe, and inexpensive. The term auscultation is derived from the Latin for "to listen," and the technique has been used for diagnostic purposes as far back as the ancient Egyptians. Valve and septal disorders will trigger abnormal heart sounds. If a valvular disorder is detected or suspected, a test called an echocardiogram, or simply an "echo," may be ordered. Echocardiograms are sonograms of the heart and can help in the diagnosis of valve disorders as well as a wide variety of heart pathologies.

Classification of Leukocytes

When scientists first began to observe stained blood slides, it quickly became evident that leukocytes could be divided into two groups, according to whether their cytoplasm contained highly visible granules: Granular leukocytes contain abundant granules within the cytoplasm. They include neutrophils, eosinophils, and basophils (you can view their lineage from myeloid stem cells in [link]). While granules are not totally lacking in agranular leukocytes, they are far fewer and less obvious. Agranular leukocytes include monocytes, which mature into macrophages that are phagocytic, and lymphocytes, which arise from the lymphoid stem cell line.

Describe how the valves keep the blood moving in one direction.

When the ventricles contract and pressure begins to rise in the ventricles, there is an initial tendency for blood to flow back (regurgitate) to the atria. However, the papillary muscles also contract, placing tension on the chordae tendineae and holding the atrioventricular valves (tricuspid and mitral) in place to prevent the valves from prolapsing and being forced back into the atria. The semilunar valves (pulmonary and aortic) lack chordae tendineae and papillary muscles, but do not face the same pressure gradients as do the atrioventricular valves. As the ventricles relax and pressure drops within the ventricles, there is a tendency for the blood to flow backward. However, the valves, consisting of reinforced endothelium and connective tissue, fill with blood and seal off the opening preventing the return of blood.

Characteristics of Blood

When you think about blood, the first characteristic that probably comes to mind is its color. Blood that has just taken up oxygen in the lungs is bright red, and blood that has released oxygen in the tissues is a more dusky red. This is because hemoglobin is a pigment that changes color, depending upon the degree of oxygen saturation. Blood is viscous and somewhat sticky to the touch. It has a viscosity approximately five times greater than water. Viscosity is a measure of a fluid's thickness or resistance to flow, and is influenced by the presence of the plasma proteins and formed elements within the blood. The viscosity of blood has a dramatic impact on blood pressure and flow. Consider the difference in flow between water and honey. The more viscous honey would demonstrate a greater resistance to flow than the less viscous water. The same principle applies to blood. The normal temperature of blood is slightly higher than normal body temperature—about 38 °C (or 100.4 °F), compared to 37 °C (or 98.6 °F) for an internal body temperature reading, although daily variations of 0.5 °C are normal. Although the surface of blood vessels is relatively smooth, as blood flows through them, it experiences some friction and resistance, especially as vessels age and lose their elasticity, thereby producing heat. This accounts for its slightly higher temperature. The pH of blood averages about 7.4; however, it can range from 7.35 to 7.45 in a healthy person. Blood is therefore somewhat more basic (alkaline) on a chemical scale than pure water, which has a pH of 7.0. Blood contains numerous buffers that actually help to regulate pH. Blood constitutes approximately 8 percent of adult body weight. Adult males typically average about 5 to 6 liters of blood. Females average 4-5 liters.

Coronary Circulation

You will recall that the heart is a remarkable pump composed largely of cardiac muscle cells that are incredibly active throughout life. Like all other cells, a cardiomyocyte requires a reliable supply of oxygen and nutrients, and a way to remove wastes, so it needs a dedicated, complex, and extensive coronary circulation. And because of the critical and nearly ceaseless activity of the heart throughout life, this need for a blood supply is even greater than for a typical cell. However, coronary circulation is not continuous; rather, it cycles, reaching a peak when the heart muscle is relaxed and nearly ceasing while it is contracting.

Heart Valves

With the atria and major vessels removed, all four valves are clearly visible, although it is difficult to distinguish the three separate cusps of the tricuspid valve.

Why do the cardiac muscles cells demonstrate autorhythmicity?

Without a true resting potential, there is a slow influx of sodium ions through slow channels that produces a prepotential that gradually reaches threshold.

Composition of Blood

You have probably had blood drawn from a superficial vein in your arm, which was then sent to a lab for analysis. Some of the most common blood tests—for instance, those measuring lipid or glucose levels in plasma—determine which substances are present within blood and in what quantities. Other blood tests check for the composition of the blood itself, including the quantities and types of formed elements. One such test, called a hematocrit, measures the percentage of RBCs, clinically known as erythrocytes, in a blood sample. It is performed by spinning the blood sample in a specialized centrifuge, a process that causes the heavier elements suspended within the blood sample to separate from the lightweight, liquid plasma (Figure). Because the heaviest elements in blood are the erythrocytes, these settle at the very bottom of the hematocrit tube. Located above the erythrocytes is a pale, thin layer composed of the remaining formed elements of blood. These are the WBCs, clinically known as leukocytes, and the platelets, cell fragments also called thrombocytes. This layer is referred to as the buffy coat because of its color; it normally constitutes less than 1 percent of a blood sample. Above the buffy coat is the blood plasma, normally a pale, straw-colored fluid, which constitutes the remainder of the sample. The volume of erythrocytes after centrifugation is also commonly referred to as packed cell volume (PCV). In normal blood, about 45 percent of a sample is erythrocytes. The hematocrit of any one sample can vary significantly, however, about 36-50 percent, according to gender and other factors. Normal hematocrit values for females range from 37 to 47, with a mean value of 41; for males, hematocrit ranges from 42 to 52, with a mean of 47. The percentage of other formed elements, the WBCs and platelets, is extremely small so it is not normally considered with the hematocrit. So the mean plasma percentage is the percent of blood that is not erythrocytes: for females, it is approximately 59 (or 100 minus 41), and for males, it is approximately 53 (or 100 minus 47).

Platelets

You may occasionally see platelets referred to as thrombocytes, but because this name suggests they are a type of cell, it is not accurate. A platelet is not a cell but rather a fragment of the cytoplasm of a cell called a megakaryocyte that is surrounded by a plasma membrane. Megakaryocytes are descended from myeloid stem cells (see [link]) and are large, typically 50-100 µm in diameter, and contain an enlarged, lobed nucleus. As noted earlier, thrombopoietin, a glycoprotein secreted by the kidneys and liver, stimulates the proliferation of megakaryoblasts, which mature into megakaryocytes. These remain within bone marrow tissue (Figure) and ultimately form platelet-precursor extensions that extend through the walls of bone marrow capillaries to release into the circulation thousands of cytoplasmic fragments, each enclosed by a bit of plasma membrane. These enclosed fragments are platelets. Each megakarocyte releases 2000-3000 platelets during its lifespan. Following platelet release, megakaryocyte remnants, which are little more than a cell nucleus, are consumed by macrophages. Platelets are relatively small, 2-4 µm in diameter, but numerous, with typically 150,000-160,000 per µL of blood. After entering the circulation, approximately one-third migrate to the spleen for storage for later release in response to any rupture in a blood vessel. They then become activated to perform their primary function, which is to limit blood loss. Platelets remain only about 10 days, then are phagocytized by macrophages. Platelets are critical to hemostasis, the stoppage of blood flow following damage to a vessel. They also secrete a variety of growth factors essential for growth and repair of tissue, particularly connective tissue. Infusions of concentrated platelets are now being used in some therapies to stimulate healing.

Congenital Heart Defects

a) A patent foramen ovale defect is an abnormal opening in the interatrial septum, or more commonly, a failure of the foramen ovale to close. (b) Coarctation of the aorta is an abnormal narrowing of the aorta. (c) A patent ductus arteriosus is the failure of the ductus arteriosus to close. (d) Tetralogy of Fallot includes an abnormal opening in the interventricular septum.

autorhythmicity

ability of cardiac muscle to initiate its own electrical impulse that triggers the mechanical contraction that pumps blood at a fixed pace without nervous or endocrine control

Leukocytes

and explore the blood slides in greater detail. The Webscope feature allows you to move the slides as you would with a mechanical stage. You can increase and decrease the magnification. There is a chance to review each of the leukocytes individually after you have attempted to identify them from the first two blood smears. In addition, there are a few multiple choice questions. Are you able to recognize and identify the various formed elements? You will need to do this is a systematic manner, scanning along the image. The standard method is to use a grid, but this is not possible with this resource. Try constructing a simple table with each leukocyte type and then making a mark for each cell type you identify. Attempt to classify at least 50 and perhaps as many as 100 different cells. Based on the percentage of cells that you count, do the numbers represent a normal blood smear or does something appear to be abnormal?

antithrombin

anticoagulant that inactivates factor X and opposes the conversion of prothrombin (factor II) into thrombin in the common pathway

defensins

antimicrobial proteins released from neutrophils and macrophages that create openings in the plasma membranes to kill cells

T and B lymphocytes ________.

are involved with specific immune function

cardiogenic area

area near the head of the embryo where the heart begins to develop 18-19 days after fertilization

Most blood enters the ventricle during ________.

atrial diastole

In which septum is it normal to find openings in the adult?

atrioventricular septum

baroreceptor reflex

autonomic reflex in which the cardiac centers monitor signals from the baroreceptor stretch receptors and regulate heart function based on blood flow

hypoxemia

below-normal level of oxygen saturation of blood (typically <95 percent)

leukopenia

below-normal production of leukocytes

pulmonary circuit

blood flow to and from the lungs

systemic circuit

blood flow to and from virtually all of the tissues of the body

serum

blood plasma that does not contain clotting factors

plasmin

blood protein active in fibrinolysis

cross matching

blood test for identification of blood type using antibodies and small samples of blood

ABO blood group

blood-type classification based on the presence or absence of A and B glycoproteins on the erythrocyte membrane surface

Rh blood group

blood-type classification based on the presence or absence of the antigen Rh on the erythrocyte membrane surface

pericardial cavity

cavity surrounding the heart filled with a lubricating serous fluid that reduces friction as the heart contracts

formed elements

cellular components of blood; that is, erythrocytes, leukocytes, and platelets

megakaryocyte

bone marrow cell that produces platelets

circumflex artery

branch of the left coronary artery that follows coronary sulcus

coronary arteries

branches of the ascending aorta that supply blood to the heart; the left coronary artery feeds the left side of the heart, the left atrium and ventricle, and the interventricular septum; the right coronary artery feeds the right atrium, portions of both ventricles, and the heart conduction system

marginal arteries

branches of the right coronary artery that supply blood to the superficial portions of the right ventricle

Which primitive area of the heart will give rise to the right ventricle?

bulbus cordis

myocardial contractile cells

bulk of the cardiac muscle cells in the atria and ventricles that conduct impulses and contract to propel blood

The influx of which ion accounts for the plateau phase?

calcium

leukemia

cancer involving leukocytes

pulmonary capillaries

capillaries surrounding the alveoli of the lungs where gas exchange occurs: carbon dioxide exits the blood and oxygen enters

atrioventricular septum

cardiac septum located between the atria and ventricles; atrioventricular valves are located here

interatrial septum

cardiac septum located between the two atria; contains the fossa ovalis after birth

interventricular septum

cardiac septum located between the two ventricles

The two tubes that eventually fuse to form the heart are referred to as the ________.

cardiogenic tubes

coronary sulcus

sulcus that marks the boundary between the atria and ventricles

hemopoietic growth factors

chemical signals including erythropoietin, thrombopoietin, colony-stimulating factors, and interleukins that regulate the differentiation and proliferation of particular blood progenitor cells

cytokines

class of proteins that act as autocrine or paracrine signaling molecules; in the cardiovascular system, they stimulate the proliferation of progenitor cells and help to stimulate both nonspecific and specific resistance to disease

The first heart sound represents which portion of the cardiac cycle?

closing of the atrioventricular valves

atrioventricular (AV) node

clump of myocardial cells located in the inferior portion of the right atrium within the atrioventricular septum; receives the impulse from the SA node, pauses, and then transmits it into specialized conducting cells within the interventricular septum

pacemaker

cluster of specialized myocardial cells known as the SA node that initiates the sinus rhythm

agglutination

clustering of cells into masses linked by antibodies

Prothrombin is converted to thrombin during the ________.

common pathway

erythrocyte

commonly known as a red blood cell (or RBC), is by far the most common formed element: A single drop of blood contains millions of erythrocytes and just thousands of leukocytes. Specifically, males have about 5.4 million erythrocytes per microliter (µL) of blood, and females have approximately 4.8 million per µL. In fact, erythrocytes are estimated to make up about 25 percent of the total cells in the body. As you can imagine, they are quite small cells, with a mean diameter of only about 7-8 micrometers (µm) (Figure). The primary functions of erythrocytes are to pick up inhaled oxygen from the lungs and transport it to the body's tissues, and to pick up some (about 24 percent) carbon dioxide waste at the tissues and transport it to the lungs for exhalation. Erythrocytes remain within the vascular network. Although leukocytes typically leave the blood vessels to perform their defensive functions, movement of erythrocytes from the blood vessels is abnormal.

P wave

component of the electrocardiogram that represents the depolarization of the atria

QRS complex

component of the electrocardiogram that represents the depolarization of the ventricles and includes, as a component, the repolarization of the atria

T wave

component of the electrocardiogram that represents the repolarization of the ventricles

carbaminohemoglobin

compound of carbon dioxide and hemoglobin, and one of the ways in which carbon dioxide is carried in the blood

thrombocytopenia

condition in which there are too few platelets, resulting in abnormal bleeding (hemophilia)

thrombocytosis

condition in which there are too many platelets, resulting in abnormal clotting (thrombosis)

A molecule of hemoglobin ________.

consists of four globin proteins, each bound to a molecule of heme

autonomic tone

contractile state during resting cardiac activity produced by mild sympathetic and parasympathetic stimulation

The production of healthy erythrocytes depends upon the availability of ________.

copper, zinc, and vitamin B12

natural killer (NK) cells

cytotoxic lymphocytes capable of recognizing cells that do not express "self" proteins on their plasma membrane or that contain foreign or abnormal markers; provide generalized, nonspecific immunity

anemia

deficiency of red blood cells or hemoglobin

cardiac notch

depression in the medial surface of the inferior lobe of the left lung where the apex of the heart is located

hemolysis

destruction (lysis) of erythrocytes and the release of their hemoglobin into circulation

sinus venosus

develops into the posterior portion of the right atrium, the SA node, and the coronary sinus

bone marrow biopsy

diagnostic test of a sample of red bone marrow

cardiac reserve

difference between maximum and resting CO

lysozyme

digestive enzyme with bactericidal properties

filling time

duration of ventricular diastole during which filling occurs

leukocyte

e, commonly known as a white blood cell (or WBC), is a major component of the body's defenses against disease. Leukocytes protect the body against invading microorganisms and body cells with mutated DNA, and they clean up debris. Platelets are essential for the repair of blood vessels when damage to them has occurred; they also provide growth factors for healing and repair. See [link] for a summary of leukocytes and platelets.

polycythemia

elevated level of hemoglobin, whether adaptive or pathological

totipotent stem cell

embryonic stem cell that is capable of differentiating into any and all cells of the body; enabling the full development of an organism

The process by which leukocytes squeeze through adjacent cells in a blood vessel wall is called ________.

emigration

The ________ layer secretes chemicals that help to regulate ionic environments and strength of contraction and serve as powerful vasoconstrictors.

endocardium

Which of the following is not important in preventing backflow of blood?

endocardium

thrombin

enzyme essential for the final steps in formation of a fibrin clot

hemorrhage

excessive bleeding

thrombosis

excessive clot formation

leukocytosis

excessive leukocyte proliferation

auricle

extension of an atrium visible on the superior surface of the heart

papillary muscle

extension of the myocardium in the ventricles to which the chordae tendineae attach

negative inotropic factors

factors that negatively impact or lower heart contractility

positive inotropic factors

factors that positively impact or increase heart contractility

common pathway

final coagulation pathway activated either by the intrinsic or the extrinsic pathway, and ending in the formation of a blood clot

septum primum

flap of tissue in the fetus that covers the foramen ovale within a few seconds after birth

afterload

force the ventricles must develop to effectively pump blood against the resistance in the vessels

lymphoma

form of cancer in which masses of malignant T and/or B lymphocytes collect in lymph nodes, the spleen, the liver, and other tissues

coagulation

formation of a blood clot; part of the process of hemostasis

hemophilia

genetic disorder characterized by inadequate synthesis of clotting factors

erythropoietin (EPO)

glycoprotein that triggers the bone marrow to produce RBCs; secreted by the kidney in response to low oxygen levels

colony-stimulating factors (CSFs)

glycoproteins that trigger the proliferation and differentiation of myeloblasts into granular leukocytes (basophils, neutrophils, and eosinophils)

fibrinolysis

gradual degradation of a blood clot

basophils

granulocytes that stain with a basic (alkaline) stain and store histamine and heparin

neutrophils

granulocytes that stain with a neutral dye and are the most numerous of the leukocytes; especially active against bacteria

polymorphonuclear

having a lobed nucleus, as seen in some leukocytes

The earliest organ to form and begin function within the developing human is the ________.

heart

globin

heme-containing globular protein that is a constituent of hemoglobin

hemocytoblast

hemopoietic stem cell that gives rise to the formed elements of blood

globulins

heterogeneous group of plasma proteins that includes transport proteins, clotting factors, immune proteins, and others

thrombopoietin

hormone secreted by the liver and kidneys that prompts the development of megakaryocytes into thrombocytes (platelets)

reticulocyte

immature erythrocyte that may still contain fragments of organelles

Which of the following plasma proteins is not produced by the liver?

immunoglobulin

plasma

in blood, the liquid extracellular matrix composed mostly of water that circulates the formed elements and dissolved materials throughout the cardiovascular system

valve

in the cardiovascular system, a specialized structure located within the heart or vessels that ensures one-way flow of blood

Hemophilia is characterized by ________.

inadequate production of clotting factors

universal recipient

individual with type AB+ blood

universal donor

individual with type O− blood

thalassemia

inherited blood disorder in which maturation of RBCs does not proceed normally, leading to abnormal formation of hemoglobin and the destruction of RBCs

extrinsic pathway

initial coagulation pathway that begins with tissue damage and results in the activation of the common pathway

intrinsic pathway

initial coagulation pathway that begins with vascular damage or contact with foreign substances, and results in the activation of the common pathway

isovolumic ventricular relaxation phase

initial phase of the ventricular diastole when pressure in the ventricles drops below pressure in the two major arteries, the pulmonary trunk, and the aorta, and blood attempts to flow back into the ventricles, producing the dicrotic notch of the ECG and closing the two semilunar valves

vascular spasm

initial step in hemostasis, in which the smooth muscle in the walls of the ruptured or damaged blood vessel contracts

endocardium

innermost layer of the heart lining the heart chambers and heart valves; composed of endothelium reinforced with a thin layer of connective tissue that binds to the myocardium

epicardium

innermost layer of the serous pericardium and the outermost layer of the heart wall

fibrin

insoluble, filamentous protein that forms the structure of a blood clo

heart block

interruption in the normal conduction pathway

The cardiac cycle consists of a distinct relaxation and contraction phase. Which term is typically used to refer ventricular contraction while no blood is being ejected?

isovolumic contraction

sinoatrial (SA) node

known as the pacemaker, a specialized clump of myocardial conducting cells located in the superior portion of the right atrium that has the highest inherent rate of depolarization that then spreads throughout the heart

People with ABO blood type O ________.

lack both antigens A and B on their erythrocytes

pulmonary trunk

large arterial vessel that carries blood ejected from the right ventricle; divides into the left and right pulmonary arteries

inferior vena cava

large systemic vein that returns blood to the heart from the inferior portion of the body

superior vena cava

large systemic vein that returns blood to the heart from the superior portion of the body

coronary sinus

large, thin-walled vein on the posterior surface of the heart that lies within the atrioventricular sulcus and drains the heart myocardium directly into the right atrium

endothelium

layer of smooth, simple squamous epithelium that lines the endocardium and blood vessels

pulmonary arteries

left and right branches of the pulmonary trunk that carry deoxygenated blood from the heart to each of the lungs

The myocardium would be the thickest in the _______

left ventricle

granular leukocytes

leukocytes with abundant granules in their cytoplasm; specifically, neutrophils, eosinophils, and basophils

agranular leukocytes

leukocytes with few granules in their cytoplasm; specifically, monocytes, lymphocytes, and NK cells

blood

liquid connective tissue composed of formed elements—erythrocytes, leukocytes, and platelets—and a fluid extracellular matrix called plasma; component of the cardiovascular system

Aging and damaged erythrocytes are removed from the circulation by ________.

macrophages

heart bulge

prominent feature on the anterior surface of the heart, reflecting early cardiac development

artificial pacemaker

medical device that transmits electrical signals to the heart to ensure that it contracts and pumps blood to the body

The cardiovascular centers are located in which area of the brain?

medulla oblongata

Of the three germ layers that give rise to all adult tissues and organs, which gives rise to the heart?

mesoderm

Which valve separates the left atrium from the left ventricle?

mitral

oxyhemoglobin

molecule of hemoglobin to which oxygen is bound

albumin

most abundant plasma protein, accounting for most of the osmotic pressure of plasma

cardiomyocyte

muscle cell of the heart

pectinate muscles

muscular ridges seen on the anterior surface of the right atrium

interatrial band

nd (also, Bachmann's bundle) group of specialized conducting cells that transmit the impulse directly from the SA node in the right atrium to the left atrium

Which portion of the ECG corresponds to repolarization of the atria?

none of the above: atrial repolarization is masked by ventricular depolarization

sinus rhythm

normal contractile pattern of the heart

heart rate (HR)

number of times the heart contracts (beats) per minute

ventricle

one of the primary pumping chambers of the heart located in the lower portion of the heart; the left ventricle is the major pumping chamber on the lower left side of the heart that ejects blood into the systemic circuit via the aorta and receives blood from the left atrium; the right ventricle is the major pumping chamber on the lower right side of the heart that ejects blood into the pulmonary circuit via the pulmonary trunk and receives blood from the right atrium

mesoderm

one of the three primary germ layers that differentiate early in embryonic development

atrioventricular valves

one-way valves located between the atria and ventricles; the valve on the right is called the tricuspid valve, and the one on the left is the mitral or bicuspid valve

foramen ovale

opening in the fetal heart that allows blood to flow directly from the right atrium to the left atrium, bypassing the fetal pulmonary circuit

fossa ovalis

oval-shaped depression in the interatrial septum that marks the former location of the foramen ovale

hemoglobin

oxygen-carrying compound in erythrocytes

cardiac plexus

paired complex network of nerve fibers near the base of the heart that receive sympathetic and parasympathetic stimulations to regulate HR

small cardiac vein

parallels the right coronary artery and drains blood from the posterior surfaces of the right atrium and ventricle; drains into the great cardiac vein

hypertrophic cardiomyopathy

pathological enlargement of the heart, generally for no known reason

cardiac cycle

period of time between the onset of atrial contraction (atrial systole) and ventricular relaxation (ventricular diastole)

systole

period of time when the heart muscle is contracting

diastole

period of time when the heart muscle is relaxed and the chambers fill with blood

macrophage

phagocytic cell of the myeloid lineage; a matured monocyte

target heart rate

range in which both the heart and lungs receive the maximum benefit from an aerobic workout

heme

red, iron-containing pigment to which oxygen binds in hemoglobin

Frank-Starling mechanism

relationship between ventricular stretch and contraction in which the force of heart contraction is directly proportional to the initial length of the muscle fiber

epicardial coronary arteries

surface arteries of the heart that generally follow the sulci

trabeculae carneae

ridges of muscle covered by endocardium located in the ventricles

Which chamber initially receives blood from the systemic circuit?

right atrium

ventricular ejection phase

second phase of ventricular systole during which blood is pumped from the ventricle

cardiac reflexes

series of autonomic reflexes that enable the cardiovascular centers to regulate heart function based upon sensory information from a variety of visceral sensors

heparin

short-acting anticoagulant stored in mast cells and released when tissues are injured, opposes prothrombin

interleukins

signaling molecules that may function in hemopoiesis, inflammation, and specific immune responses

mesothelium

simple squamous epithelial portion of serous membranes, such as the superficial portion of the epicardium (the visceral pericardium) and the deepest portion of the pericardium (the parietal pericardium)

primitive heart tube

singular tubular structure that forms from the fusion of the two endocardial tubes

heart sounds

sounds heard via auscultation with a stethoscope of the closing of the atrioventricular valves ("lub") and semilunar valves ("dub")

myocardial conducting cells

specialized cells that transmit electrical impulses throughout the heart and trigger contraction by the myocardial contractile cells

internodal pathways

specialized conductile cells within the atria that transmit the impulse from the SA node throughout the myocardial cells of the atrium and to the AV node

Purkinje fibers

specialized myocardial conduction fibers that arise from the bundle branches and spread the impulse to the myocardial contraction fibers of the ventricles

endocardial tubes

stage in which lumens form within the expanding cardiogenic cords, forming hollow structures

pluripotent stem cell

stem cell that derives from totipotent stem cells and is capable of differentiating into many, but not all, cell types

chordae tendineae

string-like extensions of tough connective tissue that extend from the flaps of the atrioventricular valves to the papillary muscles

anticoagulant

substance such as heparin that opposes coagulation

anterior interventricular sulcus

sulcus located between the left and right ventricles on the anterior surface of the heart

posterior interventricular sulcus

sulcus located between the left and right ventricles on the anterior surface of the heart

electrocardiogram (ECG)

surface recording of the electrical activity of the heart that can be used for diagnosis of irregular heart function; also abbreviated as EKG

tricuspid valve

term used most often in clinical settings for the right atrioventricular valve

myocardium

thickest layer of the heart composed of cardiac muscle cells built upon a framework of primarily collagenous fibers and blood vessels that supply it and the nervous fibers that help to regulate it

buffy coat

thin, pale layer of leukocytes and platelets that separates the erythrocytes from the plasma in a sample of centrifuged blood

embolus

thrombus that has broken free from the blood vessel wall and entered the circulation

bone marrow transplant

treatment in which a donor's healthy bone marrow with its stem cells replaces diseased or damaged bone marrow of a patient

Which of the following lists the valves in the order through which the blood flows from the vena cava through the heart?

tricuspid, pulmonary semilunar, bicuspid, aortic semilunar

The pulmonary trunk and aorta are derived from which primitive heart structure?

truncus arteriosus

cardiogenic cords

two strands of tissue that form within the cardiogenic area

memory cell

type of B or T lymphocyte that forms after exposure to a pathogen

myeloid stem cells

type of hemopoietic stem cell that gives rise to some formed elements, including erythrocytes, megakaryocytes that produce platelets, and a myeloblast lineage that gives rise to monocytes and three forms of granular leukocytes (neutrophils, eosinophils, and basophils)

lymphoid stem cells

type of hemopoietic stem cells that gives rise to lymphocytes, including various T cells, B cells, and NK cells, all of which function in immunity

murmur

unusual heart sound detected by auscultation; typically related to septal or valve defects

semilunar valves

valves located at the base of the pulmonary trunk and at the base of the aorta

The first step in hemostasis is ________.

vascular spasm

pulmonary veins

veins that carry highly oxygenated blood into the left atrium, which pumps the blood into the left ventricle, which in turn pumps oxygenated blood into the aorta and to the many branches of the systemic circuit

Ventricular relaxation immediately follows ________.

ventricular repolarization

great cardiac vein

vessel that follows the interventricular sulcus on the anterior surface of the heart and flows along the coronary sulcus into the coronary sinus on the posterior surface; parallels the anterior interventricular artery and drains the areas supplied by this vessel

posterior cardiac vein

vessel that parallels and drains the areas supplied by the marginal artery branch of the circumflex artery; drains into the great cardiac vein

middle cardiac vein

vessel that parallels and drains the areas supplied by the posterior interventricular artery; drains into the great cardiac vein

coronary veins

vessels that drain the heart and generally parallel the large surface arteries

anterior cardiac veins

vessels that parallel the small cardiac arteries and drain the anterior surface of the right ventricle; bypass the coronary sinus and drain directly into the right atrium

bilirubin

yellowish bile pigment produced when iron is removed from heme and is further broken down into waste products