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Anatomy and Physiology
of the Circulatory System
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You may print this workbook to use while you view the module online, take notes for review, and/or use for offline study.
Table of Contents
Introduction ...................................................................................... 3
Learning Objectives ......................................................................... 4
A. Role of the Heart and Circulatory System ............................... 5
B. Anatomy of the Heart ................................................................. 13
C. Cardiac Cycle .............................................................................. 22
D. Cardiac Conduction .................................................................... 35
E. Vascular Anatomy ....................................................................... 44
F. Blood ............................................................................................. 57
References ......................................................................................... 63
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Introduction Welcome to the Anatomy and Physiology of the Circulatory System module.
Here, we will provide an overview of the role of the circulatory system, including an introduction to the heart, blood, and blood vessels.
We will go into detail regarding cardiac anatomy, coronary circulation, the cardiac cycle, and cardiac conduction.
We will discuss the anatomy of systemic blood vessels, including the structure of the vasculature, major arteries and veins of the systemic circulation, and the abdominal aorta.
Finally, we will discuss the role of blood and specific blood components.
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Learning Objectives After completing this module, you should be able to:
Diagram the basic structures of the heart, including atria, ventricles, and major vessels.
Describe the general function of the heart, the cardiac cycle, and the heart’s role in circulation.
Explain cardiac output, and how this may be affected in disease.
Review basic electrical conduction pathways in the heart and relate this to the electrocardiogram (ECG).
Diagram the structure of vessel walls.
List the major veins and arteries of systemic circulation.
List the major functions of blood.
List the formed elements and describe their functions.
Discuss the components of blood plasma.
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A. Role of the Heart and Circulatory System Overview
The circulatory system is an organ system that transports blood and nutrients through the body.
In this section, we will introduce the functions of major circulatory system components including the heart, blood, and blood vessels.
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Appearance
The heart, along with its covering, the pericardium, occupies a space between the lung cavities called the middle mediastinum. The pericardium is a serous membrane containing inner and outer layers with fluid in between. The fluid allows the inner visceral pericardium to glide smoothly against the outer parietal pericardium.1
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Heart is a Double Pump
The heart is a muscular pump that serves two functions. The right side of the heart collects blood from the tissues of the body and pumps it to the lungs which replenish the blood with oxygen. The left side of the heart collects blood from the lungs and pumps it to the tissues of the body where the oxygen is utilized.1
The cardiovascular system distributes blood, which has four primary functions:
Transportation of oxygen, carbon dioxide, nutrients, wastes, hormones, and cells;
Regulation of pH, temperature, and osmotic pressure;
Protection against foreign substances and pathogens by humoral and cellular immune surveillance; and
Prevention of excessive blood loss through the mechanism of clotting.2
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Arteries, Veins, Capillaries
Blood leaves the heart through the major arteries which branch into progressively smaller arteries and arterioles. The smooth muscle cells wrapped around arteries and arterioles play an important role in determining blood pressure. These in turn branch into a network of billions of vessels with the smallest diameter – the capillaries.2,3
Capillaries are only one endothelial cell thick, making them both thin and fragile. The exchange of oxygen, carbon dioxide, and other molecules takes place through the capillary wall.2
From the capillaries, blood flows into venules, which then become veins and eventually form the major veins which return blood to the heart.2
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Knowledge Check 1
Choose which of the following are functions of the left side and right side of the heart. Choose all that apply.
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Knowledge Check 2
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Knowledge Check 3
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Summary
Now, take a moment to summarize the key points from this section:
The right side of the heart collects blood from tissues, while the left side of the heart pumps blood to tissues.
The primary functions of blood include transportation of oxygen and carbon dioxide, regulation of pH and temperature, protection against foreign substances, and prevention of excessive blood loss (via clotting).
Arteries and arterioles carry blood AWAY from the heart, while veins and venules carry blood to the heart.
Capillaries consist of a single layer of endothelial cells and are the site of oxygen and carbon dioxide exchange.
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B. Anatomy of the Heart Introduction
The heart is a complex organ consisting of multiple compartments, known as chambers, with each chamber serving a distinct function.
Blood moves between the chambers with the assistance of a number of valves, which assure unidirectional flow.
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Overview
The heart, along with its covering, the pericardium, occupies a space between the pleural cavities called the middle mediastinum.
The heart has four chambers-- the left and right atria and the left and right ventricles.1
The right atrium is the chamber of the heart that receives oxygen-poor blood from the systemic circulation. The main vessels that deliver blood to the right atrium are the superior and inferior vena cavae – large veins which transport blood from the upper and lower parts of the body, respectively.2
The right ventricle receives blood from the right atrium and pumps it out of the heart through the pulmonary trunk. The pulmonary trunk splits into the left and right pulmonary arteries that then carry the oxygen-poor blood to the lungs.2
The left atrium is the chamber of the heart that receives oxygen-rich blood from the lungs via the pairs of left and right pulmonary veins.2,4
The left ventricle receives blood from the left atrium and pumps it out through the aorta to all of the tissues of the body.2
Because this requires more force than pumping blood to the lungs, the wall of the left ventricle is much thicker than the wall of the right ventricle. The interventricular septum separates the left ventricle from the right ventricle.1
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Knowledge Check 1
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Heart – Three Layers
The heart wall is embryologically similar to blood vessels, and is divided into three layers.5
Endocardium
The endocardial layer is thin and consists of endothelium on the surface with underlying collagenous and elastic tissue.5
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Myocardium
The myocardium is the thickest layer of the heart and consists of cardiac muscle with intervening connective tissue, blood vessels and nerves.
Heart muscle cells are known as cardiac myocytes. The contractile protein assemblies within cardiac myocytes are known as sarcomeres and these form visible striations within the cell. Each sarcomere is surrounded by the calcium-rich sarcoplasmic reticulum.
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Epicardium
The epicardium, or outer surface of the heart, consists of connective and adipose tissue covered by a serous membrane of mesothelial cells. The inner visceral pericardium is separated from the outer parietal pericardium by the pericardial space. The pericardial space normally contains a very small amount of fluid, allowing the two membranes to glide smoothly against each other.5
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Knowledge Check 5
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Knowledge Check 6
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Summary
Now, take a moment to summarize the key points from this section:
The heart consists of four chambers: the right atrium, left atrium, right ventricle, and left ventricle.
The wall of the heart is made of three layers: the endocardium, myocardium, and epicardium.
The heart is surrounded by the pericardium, a double membrane filled with fluid.
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C. Cardiac Cycle Cardiac Cycle
A single cycle of the heart’s activity can be divided into two basic stages. The first stage is systole, which represents the time of contraction and ejection of blood from the ventricles, or lower chambers of the heart. The second stage is diastole, which represents the time during which the ventricles relax and fill with blood that travels from the atria, or upper chambers of the heart.2
For a normal adult, the heart goes through this cycle some 60 to 100 times per minute. A well-trained athlete may have a resting heart rate as low as 40 to 60 beats per minute.6
The blood volume in normal adults is approximately five liters, or just over one and one quarter gallons.7
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Knowledge Check 1
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Knowledge Check 2
Match each word with its proper description.
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Cardiac Muscle
Heart muscle cells, or cardiac myocytes, are cells that are specialized to generate force.8 One distinguishing feature of cardiac myocytes is the presence of unique proteins in the cell membrane which mechanically connect the cells to one another and also provide a low resistance pathway for the rapid conduction of electrical current which is maintained by ion transport channels.8
While cardiac and skeletal muscles are both striated, cardiac cells are smaller, and the action of cardiac cells is spontaneous (involuntary) and intrinsically rhythmic, unlike the action of skeletal muscle which is voluntary.9,10
These rhythmic contractions keep the heart beating in a coordinated and normal rhythm, which in turn keeps blood circulating.
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Knowledge Check 3
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Cardiac Output
“Cardiac output” is the volume of blood pumped by the ventricles per minute. Cardiac output is a function of heart rate and stroke volume, or the volume of blood ejected from the ventricles with each cardiac cycle.11 Therefore, increasing either heart rate or stroke volume increases cardiac output.12
The “stroke volume” may be calculated by taking the difference between end-diastolic volume and end-systolic volume.13
Cardiac Output (ml/min) = heart rate (beats/min) X stroke volume (ml/beat)
Average resting heart rate: 70 beats/minute
Average resting stroke volume: 70 ml/beat
Cardiac Output = 70 (beats/min) X 70 (ml/beat) = 4,900 ml/min
Average person total blood volume: 5 liters (5,000 ml)
This means that the entire volume of blood in the circulatory system is pumped by the heart about once each minute (at rest). Cardiac output may increase up to 7-fold (35 liters/min) during vigorous exercise.14,15
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Ejection Fraction
The ejection fraction (Ef) is the fraction of blood pumped out of ventricles with each heartbeat. It may be calculated as the ratio of stroke volume to end-diastolic volume (EDV).14
EDV: End-Diastolic Volume – the volume of blood within a ventricle immediately before a contraction
ESV: End-Systolic Volume – the volume of blood left in a ventricle at the end of contraction
SV: Stroke Volume – the difference between end-diastolic and end-systolic volumes is the stroke volume, the volume of blood ejected with each beat
A left ventricular ejection fraction of 65, for example, means that 65 percent of the total amount of blood in the left ventricle is pumped out with each heartbeat.
An LVEF of <40 percent may confirm a diagnosis of systolic heart failure. Someone with diastolic failure can have a normal LVEF.
An LVEF of less than 35 percent increases the risk of life-threatening irregular heartbeats and may require an implantable cardioverter defibrillator known as an ICD.16
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Fractional Shortening
“Fractional shortening” describes the extent to which the diameter of the heart measured at rest decreases as the heart contracts to beat. Because the more efficiently the heart contracts, the more its fibers shorten, fractional shortening has been used as a measure of left ventricular performance.
Fractional shortening is calculated by taking the difference between the left ventricular end-diastolic and end-systolic internal diameters as a ratio of the left ventricular end diastolic internal diameter.17,18
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Pressure-Volume Loops/Relationships
Variables in Ventricular Function
There are several variables that affect the heart’s ability to pump effectively. These include the stretching of myocytes that occurs prior to contraction, or preload; the “load” that the heart must pump against to eject blood, or afterload; and the heart’s intrinsic contractility, or inotropy.15
These variables create unique volume-pressure relationships associated with each cardiac cycle.13
While the heart’s contractile force or inotropy is a primary determinant of blood pressure, other factors and organ systems also play key roles. Roll over the text for more information.15
Preload19,20
Preload: The stretching of cardiac myocytes that occurs at the end of diastole prior to contraction.
Preload is equal to the end-diastolic volume (EDV).
Afterload19
Afterload: The "load" that the heart must eject blood against. In simple terms, the afterload is closely related to the aortic pressure. More precisely, afterload is related to ventricular wall stress (σ), where
P = ventricular pressure
r = ventricular radius
h = wall thickness
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Inotropy21
Inotropy: (also known as “contractility”): A description of the force of muscle contraction.
Inotropy reflects heart muscle performance independent of alterations in preload and afterload.
An increase in contractility with no change in preload or afterload results in increased stroke volume by ejecting a greater volume out of the ventricle.
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Knowledge Check 4
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Knowledge Check 5
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Summary
Now, take a moment to summarize the key points from this section:
The two phases of the cardiac cycle are systole (ventricle contraction/emptying) and diastole (ventricle relaxation/filling).
Cardiac output refers to the volume of blood ejected from the ventricles in one minute, and is a function of stroke volume and heart rate.
Fractional shortening can be used as a measure of left ventricular performance.
The heart’s ability to pump is affected by preload, afterload, and contractility.
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D. Cardiac Conduction Introduction
The pumping activity of the heart is coordinated by specialized electrical activities that are collectively referred to as the cardiac conduction system. The cardiac conduction system regulates cardiac contractions.22
Cardiac Conduction System
The heart’s ability to beat spontaneously, with intrinsic rhythmicity, is made possible through a highly specialized conduction system. Cardiac cells can either spontaneously generate electrical activity (pacemaker cells) or preferentially conduct this activity throughout the chambers in a coordinated fashion. Electrical impulses begin high in the right atrium in the sinoatrial node (the primary pacemaker) and travel through specialized pathways to the ventricles, transmitting the signal to pump.10
The sequence of these impulses that regulate heart rhythm form electrical impulses that can be graphically recorded on an electrocardiogram (ECG).
We will discuss the initiation and transmission of cardiac electrical impulses and relate them to the ECG recording and cardiac contraction.
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Conduction – Sinus Node
The heart’s primary pacemaker is the sinoatrial, or SA, node. The SA node is located high in the right atrium. Signals arising within the SA node spread rapidly throughout both the right and left atria, giving rise to the P-wave, and stimulating the atria to contract.1,23
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Conduction – AV Node
From the atria, the signals travel to the atrioventricular node via the atrial internodal tracts.10
The atrioventricular, or AV node, provides an electrical connection between the atria and ventricles.10
At the AV node the impulse is delayed, allowing the atria to complete their contraction before the ventricles contract.5
The ECG signal returns to baseline while action potentials not large enough to be detected spread through the AV node and continue on to the bundle of His.23
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His-Purkinje System
From the AV node, the bundle of His and right and left bundle branches carry electrical impulses to the ventricles.10
Finally, the signal travels through the Purkinje network, which is formed of tens of thousands of connections with ventricular cardiac muscle cells, producing coordinated ventricular contraction and ejection of blood.
Depolarization of the ventricles corresponds to the QRS complex and precedes ventricular contraction.23,5
Simultaneous with the QRS complex, atrial contraction has ended and the atria are repolarizing (but this does not normally show up in the ECG).
The first negative deflection, if present, is the Q-wave, the large positive deflection is the R-wave, and if there is a negative deflection after the R-wave, it is called the S-wave.23
Toward the end of ventricular contraction, the ECG signal returns to baseline. The ventricles then repolarize after contraction, giving rise to the T-wave. The T-wave is normally the last detected potential in the cardiac cycle, thus it is followed by the P-wave of the next cycle, repeating the process.23
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Cellular Basis of Connection and Coordination Between Cardiac Myocytes
Cardiomyocytes are intimately connected with each other via interlocking finger-like formations called intercalated discs.
These specialized junctions allow the efficient transfer of ions and electrical stimuli between cells.
This efficiency is such that cardiac muscle can behave electrically as a single unit or “syncytium.”
The mechanical strength of these junctions is also important for the coordinated contraction of the heart tissue as a whole.24
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Knowledge Check 1
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Knowledge Check 2
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Knowledge Check 3
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Summary
Now, take a moment to summarize the key points from this section:
The heart’s primary pacemaker is the sinoatrial (SA) node.
From the atria, electrical signals travel to the atrioventricular node via the atrial internodal tracts.
The atrioventricular, or AV node, provides an electrical connection between the atria and ventricles.
From the AV node, the bundle of His and right and left bundle branches carry electrical impulses to the ventricles.
The Purkinje network forms connections with ventricular cardiac muscle cells, producing coordinated ventricular contraction and ejection of blood.
The electrocardiogram P-wave corresponds to atrial depolarization, the QRS complex corresponds to ventricular depolarization, and the T-wave corresponds to ventricular repolarization.
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E. Vascular Anatomy Introduction
The branching network of vessels that transports blood throughout the body is called the peripheral vascular system. This system is comprised of arteries, veins and capillaries. We will learn about the structures of these components. Then we will explore the major vessels of the two main components of the peripheral vascular system: the arterial network and the venous network.
Let’s look in detail at the structure of the vessels themselves. With the exception of the smallest vessels, the blood vessel walls are made of three layers: the tunica intima, the tunica media and the tunica adventitia.5
The structures of the blood vessel walls reflects the different functions of the two types of blood vessels.
The innermost layer, the tunica intima is made up of a squamous epithelium called the endothelium. The endothelium forms a smooth, slick surface like plastic coating in a pipe.
Smooth muscle makes up the middle layer or tunica media. This layer is thicker in arteries than in veins. The additional smooth muscle allows the arteries to stretch and recoil in response to the pressure wave felt with each heartbeat. The smooth muscle of the smaller arteries, or arterioles, can relax or contract to cause dilation or constriction of the vessel. The contraction of the arterioles provides resistance to blood flow, and raises blood pressure in the arterial network.5
The outermost layer, the tunica adventitia, is made of connective tissue.
It adds structural integrity to the vessels and protects their inner tissues.
The low pressure environment of veins allows them to have thinner walls than arteries. Major veins have flaps of tissue inside that act as valves which allow blood to flow in only one direction - back to the heart.5
Now that we know what the vessels are composed of, let’s look at the network of vessels and learn some of their roles.
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First we will look at the major arteries of systemic circulation.
The major systemic arteries are shown here. The aorta receives oxygenated blood from the heart. All the other major systemic arteries branch from the aorta.
To learn the names of the major arteries, it helps to recognize that the name usually refers to the location of, or the function of, the vessel.5
The major arteries branch off into progressively smaller vessels which eventually end in arterioles. The arterioles feed capillary beds which penetrate into organs and tissues.
This list of arteries is not all inclusive.
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Now, we will look at the major veins of the systemic circulation.
The names of the major veins also refer to the location of or the function of the vessel. You will soon recognize that each artery usually has a vein that runs next to it and that they share a common name.
The capillary beds feed into progressively larger vessels called venules, which then lead to the major veins. The blood transported by the veins empties into the superior and inferior venae cavae entering the right side of the heart.
This list of veins is not all inclusive.
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If we focus on the trunk, we find many of the most critical components of the circulatory system. After all, this is where your heart and major organs lie.
The abdominal aorta is the segment of the aorta in the abdominal cavity, beginning at the diaphragm and running downward to the point where the vessel divides into two arteries. These two vessels are called the iliac arteries.
There are various branches from the abdominal aorta that serve the kidneys, liver, spleen, intestines, stomach, spinal cord, etc. If the abdominal aorta is damaged, it is a life-threatening event.
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Knowledge Check 1
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Knowledge Check 2
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Knowledge Check 3
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Knowledge Check 4
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Knowledge Check 5
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Knowledge Check 6
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Knowledge Check 7
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Knowledge Check 8
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Summary
Take a moment to summarize the key points from this section:
Blood vessels are made up of multiple layers, including the tunica intima, tunica media, and tunica adventitia.
Arteries have a thicker muscle layer than do veins, which allows them to carry blood under high pressure.
Arteries carry oxygenated blood away from the heart to tissues.
Veins carry deoxygenated blood from the tissues to the heart.
Some of the major systemic arteries include the aorta, iliac arteries, and abdominal aorta.
Some of the major systemic veins include the superior and inferior venae cavae, iliac veins and jugular vein.
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F. Blood Functions of Blood
Blood has four general functions:
Transportation of cells oxygen, carbon dioxide, nutrients, wastes and hormones;
Regulation of pH, temperature and osmotic pressure;
Protection against foreign substances, pathogens; and
Prevention of excessive blood loss through the mechanism of clotting.2
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Blood Composition
Blood is composed of both plasma and formed elements (cells or cell fragments).
All blood cells begin development, or hematopoiesis, in the bone marrow from a common hematopoietic stem cell.
Mature blood cells and fragments of cells or platelets are released into the blood stream.
There are many different types of blood cells each with differing functions. Red blood cells, or erythrocytes, remain in blood vessels and transport oxygen from the lungs to the cells of the body.
White blood cells, on the other hand, are immune cells that travel from the blood vessels to tissue sites of inflammation or infection.
Megakaryocytes are the cellular component of platelets. While megakaryocytes remain in the bone marrow, pieces of the megakaryocytes are pinched off and released into the blood stream as platelets. Platelets aid in blood coagulation.25
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Blood Volume
The total volume of blood in an average-sized individual of 70 kilograms is 5 liters.26
When blood is centrifuged, red blood cells are forced to the bottom of the centrifuge tube.
Platelets and white blood cells form a thin whitish layer known as the “buffy coat” and the plasma component of blood occupies the top of the tube.26 White blood cells and platelets occupy less than 1 percent of the blood volume.26
Hematocrit is defined as the percentage of blood volume occupied by red blood cells and is easily measured by centrifugation of a blood sample.26
Normal hematocrit is approximately 45% in men and 42% in women.26
Plasma occupies the remaining approximately 55 to 58 percent of blood volume.26
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Plasma
Although plasma is about 90% water, it contains over 100 different dissolved solutes including nutrients, gases, hormones, various wastes and products of cell activity, ions and proteins.27
These blood proteins include albumins, globulins such as antibodies, and clotting proteins such as fibrinogen and prothrombin.26
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Knowledge Check 1
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Summary
Now, take a moment to summarize the key points from this section:
Primary functions of blood include transportation of oxygen and carbon dioxide, regulation of pH and temperature, protection against foreign substances, and prevention of excessive blood loss (via clotting).
Red blood cells are involved in oxygen transport, white blood cells fight infection, and platelets are involved in blood clotting to prevent excessive bleeding.
Hematocrit is the percentage of blood volume occupied by red blood cells and is ~ 45% in men and ~ 42% in women.
Although plasma is about 90% water, it contains over 100 different dissolved solutes.
Plasma proteins include albumins, globulins such as antibodies, and clotting proteins such as fibrinogen and prothrombin.
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References
1 Weinhaus AJ, Roberts KP. Anatomy of the Heart. Chapter 5 In: Iaizzo PA, ed. Handbook of Cardiac Anatomy, Physiology, and Devices. United States: Springer Science + Business Media, LLC; 2009:59-85.
2 Iaizzo PA. General Features of the Cardiovascular System. Chapter 1 In: Iaizzo PA, ed. Handbook of Cardiac Anatomy, Physiology, and Devices. United States: Springer Science + Business Media, LLC; 2009:3-12.
3 Bonjanov G. Blood Pressure, Heart Tones, and Diagnoses. Chapter 16 In: Iaizzo PA, ed. Handbook of Cardiac Anatomy, Physiology, and Devices. United States: Springer Science + Business Media, LLC; 2009:243-255.
4 Pulmonary Vein. Medical Dictionary. Available at: http://medical-dictionary.thefreedictionary.com/pulmonary+vein.Accessed: 5/22/2013.
5 Marieb EN. Human Anatomy and Physiology. 6th Edition. San Francisco,Calif: Pearson Benjamin Cummings; 1999:599.
6 Laskowski ER. What’s a normal heart rate? MayoClinic.com Website. Sept. 29, 2012. Available at: http://www.mayoclinic.com/health/heart-rate/an01906. Accessed 5/22/2013.
7 Heart Health Center. Blood. WebMD. Available at: http://www.webmd.com/heart/anatomy-picture-of-blood. Accessed 5/22/2013.
8 Barnett VA. Cellular Myocytes. Chapter 10 In: Iaizzo PA, ed. Handbook of Cardiac Anatomy, Physiology, and Devices. United States: Springer Science + Business Media, LLC; 2009:147-158.
9 Martini, Nath, Fundamentals of Anatomy & Physiology, 9th Edition. Chapter 10: Muscle Tissue. Cardiac Muscle Tissue. Available at:http://cwx.prenhall.com/bookbind/pubbooks/martinidemo/chapter10/medialib/CH10/html/ch10_8.html Accessed 5/22/2013.
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10 Laske TG, Shrivastav M, Iaizzo PA. The Cardiac Conduction System. Chapter 11 In: Iaizzo PA, ed. Handbook of Cardiac Anatomy, Physiology, and Devices. United States: Springer Science + Business Media, LLC; 2009:159-175.
11 Bojanov G. Blood Pressure, Heart Tones, and Diagnoses. Chapter 16 In: Iaizzo PA, ed. Handbook of Cardiac Anatomy, Physiology, and Devices. United States: Springer Science + Business Media, LLC; 2009:243-255.
12 Heart Failure (HF) (Congestive Heart Failure). The Merck Manual. Available at: http://www.merckmanuals.com/professional/cardiovascular_disorders/heart_failure/heart_failure_hf.html. Accessed 5/22/2013.
13 Loushin MK, Quill JL, Iaizzo PA. Mechanical Aspects of Cardiac Performance. Chapter 18 In: Iaizzo PA, ed. Handbook of Cardiac Anatomy, Physiology, and Devices. United States: Springer Science + Business Media, LLC; 2009:271-296.
14 Widmaier EP, Raff H, Strang KT. Vander’s Human Physiology. The Mechanisms of Body Function. New York. McGraw Hill. 2011:353-433.
15 Smith DL, Fernhall B. Advanced Cardiovascular Exercise Physiology. USA. HumanKinetics.com. Accessed 5/22/2013.
16 Cleveland Clinic Website. Understanding Your Ejection Fraction. 04/10. Review by Eileen Hsich, MD and Bruce Wilkoff, MD. Available at: http://my.clevelandclinic.org/heart/disorders/heartfailure/ejectionfraction.aspx. Accessed 5/22/2013.
17 Yoshikawa H, Suzuki M, Hashimoto G, et al. Midwall Ejection Fraction for Assessing Systolic Performance of the Hypertrophic Left Ventricle. Cardiovascular Ultrasound. 2012;10:45.
18 Kliegman: Nelson Textbook of Pediatrics, 19th ed. Echocardiography. Available at:http://www.mdconsult.com/books/page.do?eid=4-u1.0-
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B978-1-4377-0755-7..00417-6--sc0015&isbn=978-1-4377-0755-7&sid=1443224051&uniqId=411786907-20#4-u1.0-B978-1-4377-0755-7..00417-6--s0065 Accessed 5/22/2013.
19 Loushin MK, Quill JL, Iaizzo PA. Mechanical Aspects of Cardiac Performance. Chapter 18 In: Iaizzo PA, ed. Handbook of Cardiac Anatomy, Physiology, and Devices. United States: Springer Science + Business Media, LLC; 2009:271-296.
20 Preload Definition. Available at: http://medical-dictionary.thefreedictionary.com/preload.Accessed 5/22/2013.
21 Inotropy Definition. Available at: http://medical-dictionary.thefreedictionary.com/inotropy. Accessed 5/22/2013.
22 Marieb EN, Hoehn K. Human Anatomy & Physiology. 7th ed. San Francisco,Calif: Pearson Benjamin Cummings; 2007.
23 Dupre A, Vieau S, Iaizzo PA. Basic ECG Theory, 12-Lead Recordings and Their Interpretation. Chapter 17 In: Iaizzo PA, ed. Handbook of Cardiac Anatomy, Physiology, and Devices. United States: Springer Science + Business Media, LLC; 2009:258-269.
24 Noorman M, van der Heyden MA, van Veen TA, Cox MG, Hauer RN, de Bakker JM, et al. Cardiac cell-cell junctions in health and disease: Electrical versus mechanical coupling. J Mol Cell Cardiol 2009; 47: 23-31.
25 Alberts B., Johnson A., Lewis J., et al. Molecular Biology of The Cell. 4th ed. New York, NY: Garland Science; 2002: 1283-96.
26 Iaizzo PA. General Features of the Cardiovascular System. In: Iaizzo PA, ed. Handbook of Cardiac Anatomy, Physiology, and Devices. United States: Humana Press, Inc.; 2005:3-11.
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27 Marieb EN. The Cardiovascular System: Blood Vessels. In: Human Anatomy and Physiology. United States: The Benjamin/Cummings Publishing Company, Inc.; 1995:643-693.
