1. Human Circulatory System
The human circulatory system consists of the following. First is the blood. This is the circulating fluid to transport dissolved oxygen, digested food and waste products. Haemoglobin, a respiratory pigment, increases the oxygen-carrying capacity of the blood. Second is the heart, a pumping device to create a pressure difference which forces blood to flow. Third are the tubes or blood vessels. The blood must be at least partly contained in tubes in order to carry it towards the tissues and then back to the heart. Finally, it is the valves. This is the essential part of the heart structure to ensure that the blood flows in the correct directions and to prevent the backflow of blood. They are also found in the blood vessels (veins), usually where the blood is flowing slowly under low pressure.
2. Anatomy of Mammalian Heart
2.1 Gross Structure and Position
The human heart is a hollow muscular organ and is approximately the size of a person’s fist. It assumes an oblique position and tips slightly to the left. It is also located within the thoracic cavity between the lungs. Finally, it lies between the vertebral column and sternum.
2.2 Structure and Function
2.2.1 Pericardium
The pericardium is a protective sac that encloses the heart and is reinforced by a dense network of collagen fibres attaching the heart to the diaphragm, spinal column and sternum to stabilize the position of the heart and associated blood vessels in the chest cavity.
It is composed of 2 layers. There is an outer, non-distensible white fibrous layer of connective tissue. This is tough and inelastic, yet loose-fitting enough to allow the heart to move in a limited way. It also prevents the heart from being overfilled by blood or overstretched.
The second layer is an inner layer of serous tissue. It secretes fluid (pericardial fluid) into the pericardial cavity which moistens the sac and reduces friction between the beating heart and the surrounding stationary tissues.
2.2.2 Heart Wall
The wall is made up of 3 layers. The first layer is the epicardium. It is the outermost layer of serous membrane including blood capillaries, lymph capillaries and nerve fibres. This layer serves as a lubricative outer covering.
The second inner layer is the myocardium. This is a very thick median layer composed mainly of cardiac muscle tissue separated by connective tissues and including blood capillaries and nerve fibres. It provides muscular contractions that eject blood from the heart chamber.
The third layer is the endocardium. This is the innermost layer. It is thin and fibrous lined with simple squamous epithelial tissue (endothelium) and a thick subendothelial layer of elastic and collagenous fibres. It serves as a protective inner lining of the chambers and valves.
2.2.3 Heart Chambers and associated vessels
The heart has 4 chambers, 2 atria and 2 ventricles. These chambers communicate with the great vessels, specifically the superior and the inferior vena cavae, pulmonary trunk, pulmonary vein and aorta.
2.2.3.1 Atria: Receiving Chambers
Both chambers look almost identical as functional demands are very similar. It is there to collect and retain blood returning to the heart temporarily until it can pass to the respective ventricles. They are relatively thin-walled as they need to contract minimally to push blood into the ventricles, which are a short distance away; contribute little to the propulsive pumping activity of the heart.
2.2.3.1.1 Left Atrium
It receives oxygenated blood from the lungs. Blood enters via 4 pulmonary veins, 2 left and 2 right to transport blood from the lungs back to the heart.
2.2.3.1.2 Right Atrium
It receives deoxygenated blood from the general circulation of the body. Blood enter via the superior vena cava (from the body parts above the diaphragm), inferior vena cava (from body areas below the diaphragm) and the coronary sinus (collects blood draining from the myocardium).
2.2.3.2 Ventricles: Discharging Chambers
Its massive muscular ventricular walls make up most of the heart. They are the actual pumps of the heart, propelling blood into the circulation when they contract. Muscle bundles, the cone-like papillary muscles, project into the ventricular cavity. Left and right ventricles contain equal amounts of blood.
2.2.3.2.1 Left ventricle
Its myocardium is about 3 times as thick as the right ventricle. This ventricle pumps blood through the aorta to a much larger systemic circulation of the body. It needs to exert a higher pressure (6 to 7 times greater) to pump blood to a greater distance against a high peripheral resistance.
2.2.3.2.2 Right ventricle
The myocardium is thinner than the left ventricle but thicker than the atria. It only supplies to the pulmonary circulation by discharging blood into the pulmonary artery (relatively short and wide). It pumps blood a shorter distance from the heart to the lungs hence it exerts a lower pressure.
2.2.3.3 Heart Valves
Blood flows through the heart in one direction: from the atria to the ventricles and out of the great arteries. This one way traffic is enforced by the presence of 4 heart valves: the paired atrio-ventricular (AV) and the semi-lunar (SL) valves. Both types of valves normally function as one way doors.
2.2.3.3.1 Semi-Lunar Valves
They do not require muscular braces as the relative positions of the cusps are stable. They guard the point of entry of blood into large arteries and prevent regurgitation into the ventricles. Each SL valve appears as 3 pocket-like endocardial cusps. The valve closes when the sinuses fill with back-flowing blood. Aortic SL valves are at the junction of aorta and the left ventricle. Pulmonary SL valves are at the junction of the RV and pulmonary arteries
As ventricles contract and intraventricular pressure rises, blood is pushed up against SL valves forcing them to open. As ventricles relax and intraventricular pressure falls, blood flows back fron the arteries, filling cusps of SL valves and forcing them to close.
2.2.3.3.2 Atrio-Ventricular Valves
They are located at the junction of the atrial and ventricular chambers on each side of the heart, separating the upper chambers from the lower. The edges of the AV valves are supported by non-elastic strands of the chordae tendineae, which are anchored to the muscular wall of the ventricles below. When the ventricles are relaxed, the chordae tendineae are loose and the AV valves offer no resistance to the flow of blood from the atria to the ventricles. When the ventricles begin to contract, blood moving back to the atria swings the cusps together, closing the valves. At the same time, the contraction of the papillary muscles tenses the chordae tendineae and stops the cusps before they swing into the atria. The AV valve prevents the backflow of blood into the atria when ventricles are contracting. The right AV valve is the tricuspid valve (3 cusps) while the left AV valve is the bicuspid / mitral valve (2 cusps)
Blood entering the heart fills the atria, putting pressure against the AV valves and forcing them to open. Ventricles then fill up. Atria contract, forcing additional blood into the ventricles. The ventricles contract, forcing blood against the AV valves. The AV valve closes. Papillary muscles contract and the chordae tendineae tightens, preventing valves from entering the atria.
2.3 Histology of the Heart
There are 2 types of heart tissue. The contractile tissue comprises of cardiac muscle fibres / cardiac muscle cells. The conductile tissue comprises of the cardiac conducting fibres / cardiac conducting cells.
2.3.1 Cardiac Muscle Fibres / Cells
The bulk of the heart myocardium is composed of contractile muscle fibres responsible for the pumping activity of the heart. Cardiac muscle fibres ate involuntary, striated and branched. The tissue is arranged in interlacing bundles of fires with connective tissues and has 3 spiral layers of cardiac muscle which are attached to a fibrous ring (fibrous trigone) that forms the cardiac skeleton. The spiral is the most effective arrangement for squeezing blood out of the heart’s chambers
Numerous gap junctions in the intercalated discs allow ions to pass freely form cell to cell, electrically coupled by gap junctions. When the atrial or ventricular muscle mass is stimulated, the action potential spreads over the entire atrial or ventricular syncytium, causing the muscle cells in the entire chamber to contract almost in unison.
2.3.2 Cardiac Conducting Fibres
The in-built myogenic conduction system consists of non-contractile cardiac cells specialized to initiate and distribute impulses rapidly throughout the heart. It causes the heart to depolarize and contract in an orderly sequential manner from atria to ventricles. Thus the heart beats nearly as one cell. No neurons are present in the wall of the heart.
3. Action of the heart to initiate a heartbeat
The SAN a.k.a. the pacemaker is located in the right atrial wall, near the entrance of the superior vena cava. It maintains the heart’s pumping rhythm by determining the rate at which the heart contracts.
The specialized pacemaker cells are autorhythmic and will spontaneously depolarize initiating electrical impulses of action potentials which spread rapidly through cardiac muscle cells of both atria through gap junctions in the intercalated discs. As a result, the atria contract in unison.
The impulses spread slower via the intermodal pathway to a relay point called the atrio-ventricular node (AVN), located in the wall near the junction between the right atrium and the right ventricle. Since gap junctions do not connect the atria and ventricles, the connective tissue that separates atria from ventricle cannot transmit depolarization. The internodal pathway is the only electrical connection between them. This delay about 0.1 seconds before passing to the ventricles ensures that the atria will contract first and empty completely before the ventricles contract.
Upon reaching the AVN, the impulses again spread rapidly to the Bundle of His, the heft and right bundle branches through the septum and throughout the ventricular wall via the Purkinje or Purkyne fibres.
A moderator band bridges the interventricular septum and the papillary muscles to deliver the impulse and allow the papillary muscles to contract prior to ventricular cardiac muscles. Thus, the chordate tendineae is taut and the AV valves are close to prevent backflow of blood from the ventricles into the atria. The wringing contraction of the ventricles from the apex upwards to the base of the heart forces most of the blood out of the ventricles into the aorta and pulmonary arteries.
3.1 Flow of Blood through the heart
Venous blood (deoxygenated) from the body tissues enters the right atrium through the superior and inferior vena cavae. It flows through the right AV valve into the right ventricle. At the same time, oxygenated blood also returns from lungs to the left atrium via the pulmonary veins. The blood flows through the mitral / bicuspid valve into the left ventricle.
Upon ventricular contraction, blood flows through the right pulmonary SL valve and into the pulmonary arteries. It travels to the lungs for oxygen exchange and then returns to the heart through the pulmonary veins. The oxygenated blood in the left ventricle leaves the heart through the aortic SL valve into the aorta.
There is the sino atrial node (SAN) which is a minute cell mass of diffusely orientated cardiac fibres; it is crescent shaped. It is located on the right atrial wall at the entrance of the superior vena cava.
It initiates a heartbeat independently of the central nervous system (CNS), establishing the rhythm for the heartbeat. The heart’s pacemaker and its rhythm determine the heart rate. This is because there is no other region of conduction that has a faster depolarization rate. The SAN sets the heart pace. The pacemaker’s activity results from the spontaneous depolarization of the SAN at regular intervals, 70 to 80 times a minute.
The SAN makes contact with the adjacent atrial muscle cells and causes them to be depolarized by electrical conduction through the gap junctions of the intercalated discs of the cardiac muscles. The atrial cells then cause neighbouring cells to initiate an action potential. A wave of electrical activity is spread throughout the right atrium then to the left atrium.
The atrio ventricular node (AVN) is located in the inferior portion of the interatrial septum immediately above the tricuspid valve. Its function is to receive a wave of depolarization from the SAN via gap junctions throughout the atria and via the internodal pathway. Impulse is delayed about 0.1 second, allowing the atria to respond and complete their contraction before ventricles contract. The signaling impulse then passes rapidly through the rest of the system.
The bundle of His is located in the inferior part of the interatrial septum. Its function is to receive the impulse from the AVN. Although the atria and ventricles are next to each other, they are not connected by a gap junction. The bundle of His is the only electrical junction between the atria and ventricles.
The function of the right and left bundle branches is to course the impulses along the interventricular septum toward the apex of the heart.
Purkinje fibres are hundreds of tiny, large diameter, specialized cardiac muscle fibres called cardiac conducting myofibres. They complete the pathway through the interventricular septum; penetrate into the heart apex and then superiorly into the ventricular walls. Their function is to ensure excitation of septal cells. Together with cell to cell transmission of impulse by the ventricular muscle cells, the Purkinje fibres are responsible for the bulk of the ventricular depolarization. They supply the papillary muscles before supplying the lateral walls of the ventricles. This ensures that the papillary muscles are contracting to take up the slack on the chordae tendineae before the full force of the ventricular contraction hurls blood against the AV valve flaps. Because of the large diameter of these fibres, an impulse travelling along them is conducted rapidly and directly into the cardiac muscle, so that all the cardiac muscle cells contract in unison, producing coordinated pumping effort.
4. The Cardiac Cycle
Cardiodynamics is the movement and force generated during cardiac contractions. The human body contains 4 to 6 litres of blood, but the heart takes about 1 minute to pump this volume of blood throughout the body. On average, the adult heart pumps about 700 litres of blood throughout the body every day.
The period between the start of one heartbeat and the beginning of the next is a single cardiac cycle. The cardiac cycle therefore includes alternating periods of contraction (systole) and relaxation (diastole) of the atria and ventricles.
Fluids tend to move from an area of high pressure to one with lower pressure. In the course of the cardiac cycle, the pressure within each chamber rises in systole and falls in diastole. Valves between adjacent chambers help ensure blood flows in the desired direction, but the mere presence of valves is not enough. Blood will flow from one chamber to another only if pressure in the first chamber exceeds that in the second. This basic principle governs the movement of blood between atria and ventricles, between ventricles and arterial trunks and between major veins and the atria.
The correct pressure relationships are dependent on the careful timing of contractions. For example, blood movement could not occur in the desired direction ia an atrium and its ventricle contracted at precisely at the same moment.
The elaborate pacemaking and conducting systems normally provide the required spacing between atrial and ventricular systoles. As a result, atrial systole and ventricular systole do not occur at the same time, and atrial diastole and ventricular diastole differ in duration.
4.1 Electrical Events (Electrocardiogram)
The electrical changes occurring as the heart contracts can be measured using an electrocardiograph. It is a device that converts electrical changes during heart activity to movements of a pen on paper, or a spot of light on a cathode ray tube (CRT) producing an electrocardiogram (ECG or EKG).
The ECG has electrodes which when placed at certain points on the body can detect the electrical activity in the heart. To enhance contact, a jelly containing on electrolyte is put on the skin where the electrodes are attached.
Any deviation from the normal rate or sequence of excitation is called cardiac arrhythmia. It is the result of structural and functional disorders such as abnormal heart beat rhythm or damage to the myocardium. Because the electrical activity of the heart is sensitive to the changes in ion concentration, especially potassium ions, abnormal electrolyte levels in the blood may alter ECG.
A typical ECG consists of a series of 3 distinguishable waves called deflection waves.
4.1.1 P wave
It results from the movement of the depolarization wave from the SA node through the atria. It is a small deflection caused by the depolarization of the atrial muscle. The atrial contraction brings about 100 msec after the start of the p wave.
A deflection corresponding to atrial repolarization is not visible because it occurs while the ventricles are depolarizing. The electrical events are masked by the QRS complex.
4.1.2 QRS complex
This results from ventricular depolarization and precedes ventricular contraction. It is a relatively strong signal because the mass of ventricular muscle is much larger than that of the atria. Ventricles begin contracting shortly after the peak of the R wave.
4.1.3 T wave
It indicates ventricular repolarization. The repolarization is slower than the depolarization, so the T wave is more spread out and has a lower amplitude than the QRS complex.
4.2 Mechanical Events – Pressure / Volume changes
It is marked by a succession of pressure changes in various chambers and vessels. As the chambers contract, pressure increases and outflow valves open; blood then flows from the areas of higher pressure to areas of lower blood pressure. Periods of systole are when there is a contraction of the heart and the ejection of blood. Periods of diastole are when there is the relaxation of the heart and the filling of blood. Although pressures are lower in the right atrium and right ventricle, both sides of the heart contract at the same time and eject equal volumes of blood.
4.2.1 Atrial systole (100 msec)
End diastolic volume (EDV) is affected by the filling time (duration of ventricular diastole) and venous return (rate of blood flow over this period). The cardiac cycle begins with atrial systole. As the atria contract, rising atrial pressures push blood into the ventricles through the open right and left AV valves. At the start of atrial systole, the ventricles are already filled to about 70% of capacity and the atrial systole essentially “tops them off” by providing the additional 30% (the ventricles filled passively during the previous cardiac cycle). At the end of atrial systole, each ventricle contains the maximum amount of blood that it will hold in the cardiac cycle. That quantity is called the EDV. The EDV in the person standing at rest is about 130 ml.
4.2.2 Atrial diastole (700 msec)
Relaxation of the atria, the right atrium refills with blood from the large veins (vena cavae) leading to the heart from the body while the left atrium refills with blood from the lungs.
4.2.3 Ventricular systole (270 msec)
As the atrial systole ends, ventricular systole begins. As the pressure inside the ventricles rise above those in the atria, the AV valves swing shut. During this stage of ventricle systole, the ventricles are contracting. Blood flow has yet to occur, because ventricular pressures are not high enough to force open the semi-lunar valves and push blood into the pulmonary or aortic trunks. Over this period, the ventricles contract and ventricular pressures rise but blood flow does not occur. The ventricle is now in the period of isovolumetric contraction. During isovolumetric contraction, all the heart valves are closed and the volume of the ventricle remains constant and ventricular pressure rises.
Once pressure in the ventricles exceed that in the arterial trunks, the semilunar valves open and the blood flows into the pulmonary and aortic trunks. This point marks the beginning of the period of ventricular ejection. Ventricles now contract isotonically; muscles shorten and tension production is relatively constant. After reaching a peak, ventricular pressures gradually decline near the end of ventricular systole. During this period, each ventricle will eject approximately 80 ml of blood. This is the stroke volume (SV) of the heart.
At the end of ventricular systole, ventricular pressures fall rapidly. Blood in the aorta and the pulmonary trunks now starts to flow back into the ventricles and this movement closes the semilunar valves. As the backflow begins, pressures decrease in the aorta. When the semilunar valves close, pressure rises again as the elastic arterial walls recoil. This small, temporary rise produces a valley in the pressure tracing that is called a dicrotic notch. The amount of blood remaining in the ventricle when the semilunar valve closes is the end-systolic volume (ESV).
4.2.4 Ventricular Diastole (430 msec)
All the heart valves are now closed and the ventricular myocardium is relaxing. Because the ventricular pressure is still higher than the atrial pressure, blood cannot flow into the ventricles. Ventricular pressures fall rapidly over this period because elasticity of the connective tissues of the heart and fibrous skeleton helps to re-expand the ventricles toward their resting dimensions.
When ventricular pressures fall below those of the atria, The atrial pressures forces the AV valve open. Blood now flows from the atria to the ventricles. Both the atria and the ventricles are now in diastole, but the ventricular pressures continue to fall as the ventricular chambers expand. Throughout this period, pressures in the ventricles are so far below most of the major veins that blood pours through the relaxed atria into the ventricles. This passive mechanism is the primary method of ventricular filling. The ventricles will be nearly three quarters full before the cardiac cycle ends.
The relatively minimal contribution that atrial systole makes to ventricular volume explains why individuals can still survive quite normally when atria have been so severely damaged so that they can no longer function. By contrast, damage to one or both ventricles can leave the heart unable to maintain blood flow through peripheral tissues and organs. A condition of heart failure then exists.
4.3 Ausculatory Events – Phonocardiogram
Contraction of the heart is accompanied by a characteristic set of sounds produced as the heart valves close during each heartbeat. Recording such sounds produces a phonocardiogram. There are 4 heart sounds associated with the cardiac cycle, although only the first and second heart sounds can be heard easily with a stethoscope. The basic rhythm of the heart is lubb-dupp, pause and so on. The sounds can be used to diagnose heart malfunctions, particularly those associated with valves failing to close properly.
4.3.1 The 1st Heart Sound (S1)
This is the “lubb” sound. It is louder, louder and more resonant than the 2nd heart sound. It reflects the AV valve closure during ventricular contraction.
4.3.2 The 2nd Heart Sound (S2)
This is a short and sharp “dupp” sound. This indicates the semilunar valves snapping shut during ventricular diastole.
4.3.3 The 3rd Heart Sound (S3)
This sound is heard occasionally and is caused by the vibration of the ventricular walls after the AV valves open and the blood gushes unto the ventricles.
4.3.4 The 4th Heart Sound (S4)
This is usually not heard. It is caused by blood rushing into the ventricles.
5. Cardiac Output
It refers to the amount of blood flowing from each ventricle per minute. It is the product of stroke volume (SV) and the heart rate.
Heart rate is determined by the rate of depolarization in autorhythmic nerves. This is slowed by parasympathetic innervations and is also made faster by sympathetic innervations. Usually, epinephrine from the adrenal medulla is made use of to make the heart rate faster.
Stroke volume is determined by the force of contraction in the ventricular myocardium. This is in turn influenced by contractility and the length-tension relationship of muscle fibres which varies with venous return.
Cardiac output provides a useful indication of ventricular efficiency over time. It is precisely adjusted so that peripheral tissues can receive an adequate circulatory supply under a variety of conditions.
When necessary, stroke volume in a normal heart can almost double and the heart rate can increase by 250%. In most healthy people, increasing both the stroke volume and the heart rate, as during vigorous exercise, cam raise the cardiac output by 300-500% from 6 liters/min to 18-30 liters/min. Trained athletes exercise at maximal levels may increase cardiac output by nearly 700% to 40 liters/min.
5.1 Regulation of Cardiac Output during Strenuous Exercise
With increased levels of muscular activity during exercise, there is increased muscle contraction of the limbs and significant changes in composition of the blood especially for oxygen, carbon dioxide and pH.
Muscles are pressed against the walls of the veins, squeezing the blood within and directing the return of the blood to the right atrium of the heart. With increased venous return, directed by the stretch receptors located in the vena cavae, stimuli are sent to the cardio-vascular centre in the brain (medulla oblongata). The excitatory region will be activated to send nervous signals via the sympathetic nerves to the sino-atrial (SAN) and the atrio-venricular nodes (AVN). The pacemakers will increase the heart rate.
The excitatory region in the cardio-vascular centre also sends signals to the adrenal glands which release epinephrine/adrenaline and norepinephrine/noradernaline into the blood. These hormones act on the cardiac muscles to increase the force of contraction which increases the stroke volume and increases the heart rate.
Also with greater venous return, the ventricular cardiac muscles are stretched to a greater extent and the force of contraction of these muscles also increased (according to Starling’s Law) as well. Hence, the stroke volume is increased.
Low levels of oxygen, increased partial pressure of carbon dioxide and decreased blood pH are detected by chemoreceptors which activate the excitatory cardio-vascular centre which also send nervous signals to the SAN and AVN to increase the heart rate.
To maintain the cardiac output and blood pressure within an acceptable range/limit during exercise, baroreceptors in the aorta and carotid sinus will activate the inhibitory cardio-vascular centre when blood pressure is too high. Nervous signals via the non-sympathetic / parasympathetic / vagus nerve will normalize the heart rate and blood pressure.
After exercise, the partial pressure of oxygen and carbon dioxide and blood pH gradually return to normal homeostatic levels. Chemoreceptors will activate the inhibitory cardio-vascular centre which restores the heart rate to normal via the vagus nerve.
6. Structure of Blood Vessels
Blood leaves the heart in the pulmonary and aortic trunks, each with an internal diameter of about 2.5 cm. The pulmonary arteries that branch from the pulmonary trunk carry blood to the lungs. The systemic arteries that branch from the aorta distribute blood to all other organs.
Within these organs, further branching occurs, creating several hundred million tiny arteries that provide blood to more than 10 billion capillaries. These capillaries, barely the diameter of a single red blood cell, form extensive, branching networks. If all the capillaries in our body were placed end to end, they will circle the globe with a combined length of over 25000 miles.
6.1 Type of Arteries
Arteries carry blood away from the heart toward capillaries. As they approach the capillaries, arteries branch repeatedly and the branches decrease in diameter. The smallest arterial branches are called arterioles. From the arterioles, blood moves into the capillaries. By regulating smooth muscles in the walls of the arterioles, the cardiovascular centre of the brain ensures that the volume, pressure and speed of blood movement through the peripheral capillaries remain within acceptable limits.
Their relatively thick, muscular walls make arteries elastic and contractile
Elasticity permits passive changes in vessel diameter in response to alterations in blood pressure. It allows arteries to absorb the pressure pulses that accompany the ventricle contractions.
Contractility of the arterial walls allows an active change in diameter, primarily under the control of the sympathetic division of the autonomic nervous system. When stimulated, arterial smooth muscles contract and thereby constrict the artery, a process called vasoconstriction. Relaxation of the smooth muscles causes an increase in the diameter of the lumen, a process called vasodilation.
6.1.1 Elastic Arteries (Conducting Arteries)
Pulmonary and aortic trunks are the largest (2.5 cm) and transport large volumes of blood away from the heart. The walls are extremely resilient. The tunica media of these vessels contains a high density of elastic fibres and relatively few smooth muscle cells.
They are able tolerate pressure changes that occur during the cardiac cycle. When ventricular systole occurs, the elastic arteries expand to cushion the sudden rise in pressure. During ventricular diastole, the elastic fibres recoil to their original dimensions, thus slowing the drop in blood pressure. This feature is important because blood pressure is the driving force behind blood flow. The greater the pressure oscillations, the greater the changes in blood flow. The elasticity of the arterial system dampens the pressure peaks and valleys that accompany the heart beat. By the time the blood reaches the arteriole, the pressure oscillations have disappeared and blood flow is continuous.
6.1.2 Muscular Arteries (Distribution Arteries)
They distribute blood to the body’s skeletal muscle and internal organs. The tunica media is thick and contains more smooth muscle cells than elastic arteries. Lumen diameter is about 0.4 cm.
6.1.3 Arterioles (Resistance Vessels)
Arterioles have very poorly defined tunica externa and the tunica media has one to two layers of smooth muscle cells. The diameter may change in response to local conditions or to sympathetic or endocrine stimulation. Vasodilation occurs when oxygen levels in the tissue are low. Changes in their diameter affect the amount of force required to push blood around the cardiovascular system. More pressure is required to push blood through a constricted vessel than through a dilated one.
6.2 Types of Veins
Veins return blood from capillaries of all tissues to the heart. The walls of veins are thinner than those of corresponding arteries. They need not be as thick as arterial walls because the blood pressure in veins is lower than that in the arteries.
6.2.1 Venules
They collect blood from capillary beds. Their internal diameter is roughly 20 microns. Venules smaller than 50 microns lack a tunica media.
6.2.2 Medium-sized Veins
Their internal diameter ranges from 2-9 mm. The tunica media is thin and contains relatively few smooth muscle cells. The thickest layer is the tunica externa which contains longitudinal bundles of elastic and collagen fibres.
6.2.3 Large Veins
This includes the superior and inferior vena cavae. All the tunica layers are present. The slender tunica media is surrounded by a thick tunica externa composed of a mixture of elastic and collagen fibres.
6.3 Histology of Vessel Walls
The walls if arteries and veins contain 3 distinct layers. They are the tunica interna or tunica intima (innermost), tunica media (middle) and tunica externa or tunica adventitia (outermost).
The tunica interna is the innermost layer. It includes the endothelial lining and an underlying layer of connective tissue with a variable number of elastic fibres. In arteries, the outer margin of the tunica interna contains a thick layer of elastic fibres called the internal elastic membrane or elastic interna.
The tunica media, the middle layer, contains concentric sheets of smooth muscle tissue in a framework of loose connective tissue. The collagen fibres bind the tunica media to the tunica interna and tunica externa. The tunica media is usually the thickest layer in the wall of a small artery. It is separated from the surrounding tunica externa by the external elastic membrane of elastic externa, a thin band of elastic fibres. The smooth muscle cells of the tunica media encircle the endothelium lining of the lumen of blood vessel. When these smooth muscles contract, the vessel decreases in diameter, when they relax, the diameter increases. Large arteries also contain layers of longitudinally arranged smooth muscle cells.
The tunica externa is the outermost layer and forms a connective tissue sheath around the vessel. In arteries, this layer contains collagen fibres with scattered bands of elastic fibres. In veins, this layer, which is thicker than the tunica media, contains networks of elastic fibres and bundles of smooth muscle cells. The connective tissue fibres of the tunica externa blend into those of adjacent tissues, stabilizing and anchoring the blood vessel.
6.4 Types of Capillaries
A typical capillary consists of an endothelial tube inside a delicate basement membrane. There is neither a tunica media nor a tunica externa. The average diameter is 8 microns, very close to that of a single red blood cell. Capillary walls are thin, permitting a 2-way exchange between the blood and the surrounding interstitial fluids.
The exchange can occur quickly because firstly, the diffusion distance is short / small (one layer of squamous cells). Secondly, the blood flows through relatively slowly allowing sufficient time for diffusion or active transport of materials across the capillary walls. Thirdly, there is a steep concentration gradient of substances between blood and tissue fluid.
6.4.1 Continuous Capillaries
The capillary endothelium is a complete lining. They permit the diffusion of water, small solutes and lipid-soluble materials into the surrounding interstitial fluid but prevent the loss of blood cells and plasma proteins. They also allow pinocytosis through the movement of vesicles that form from the inner endothelial surface.
6.4.2 Fenestrated Capillaries
A fenestrated capillary has “holes” in it; the word comes from fenestra, the Latin word for window. The endothelial lining contains pores (perforations on the plasma membrane) which permit the rapid exchange of water and solutes as large as small peptides between the blood plasma and the interstitial fluid. This type of capillary is found in places where the rapid movement of materials is vital to function, such as along the absorptive areas in the intestinal tract, in endocrine organs, where movement of hormones into the blood occurs. Fenestrated capillaries are also found in the kidney, again a place where quick transit between 2 compartments is the design criterion. It is really not possible to see the fenestrations in a light microscope preparation.
6.4.3 Sinusoids
They are specialized fenestrated capillaries that are flattened and are irregular. Commonly, they have gaps between adjacent endothelial cells and the basement membrane may be incomplete or absent. They permit the free exchange of water and solutes as large as plasma proteins. They are found in abundance in the liver.
6.5 Capillary Beds
Capillaries do not function as individual units but as part of an interconnected network called capillary beds or capillary plexus. A single arteriole generally gives rise to dozens of capillaries that empty into several venules, the smallest vessels of the venous system.
The entrance to each capillary is guarded by a band of smooth muscle called precapillary sphincter. Contraction of the smooth muscle cells constricts and narrows the diameter of the capillary entrance, thereby reducing the flow of blood. Relaxation of the sphincter dilates the opening, allowing blood to enter the capillary at a faster rate.
Within the capillary bed, preferred channels provide a relatively direct means of communication between arterioles and venules. The arteriolar segment of the channel contains smooth muscles capable of altering its diameter.
7. Coronary Heart Disease
The heart works continuously and cardiac muscle cells require reliable supplies of oxygen and nutrients. The coronary circulation supplies blood to the muscles of the heart. The coronary circulation includes an extensive network of coronary blood vessels.
The left and right coronary arteries originate at the base of the ascending aorta blood pressure here is the highest in the systemic circuit and this pressure ensures a continuous flow of blood to meet the demands of active cardiac muscle tissue.
Coronary heart disease a.k.a. coronary artery disease refers to the degenerative changes in the coronary circulation due to an occlusion or obstruction of the coronary or heart arteries. One of the most common degeneration of the coronary arteries is the thickening and the toughening of arterial walls. This condition is known as arteriosclerosis. It is also related to Ischaemic Heart Disease (IHD) which results from any imbalance between the supply of oxygen and myocardial demand for them. There are 2 major forms of arteriosclerosis.
Atherosclerosis is a condition of progressive damage of the endothelial lining and the formation of lipid deposits in the tunica media.
Focal Calcification is the general degeneration of smooth muscle in the tunica media and the subsequent deposition of calcium salts. This process typically involves arteries of the limbs and genital organs.
7.1 Development of Atherosclerosis
Atherosclerosis tends to develop in persons whose blood contains elevated levels of plasma lipids, especially cholesterols, which is transported to peripheral tissues in lipoproteins.
Certain low-density lipoproteins (LDLs) are removed at a much slower rate and high levels of such LDLs remain in circulation for an extended period.
Circulating monocytes (WBC) begin removing excess cholesterol, become filled with lipid droplets (a.k.a. foam cells). They squeeze and remain under the endothelium of blood vessels where a tear or injury has occurred and eventually form a plague or atheroma, which appear as yellow fatty deposits in the tunica media.
The atheroma projects into the lumen, reducing or narrowing its size or diameter and restricting the flow of oxygenated blood to the heart muscles.
7.2 Consequences of Atherosclerosis
It may lead to hypertension / high blood pressure. This is due to the narrowing of the coronary arteries, if blood volume remains the same as before.
Thrombosis is a condition where a thrombus / clot formed at the region of atheroma in the coronary artery.
Coronary arteries damaged by atherosclerosis can be surgically by-passed with parts of a vein or artery taken from elsewhere of the body.
Stroke can also occur. If the thrombosis or embolism blocks an artery supplying part of the brain, a “stroke” is the outcome. The brain depends on blood for a continuous supply of oxygen and glucose. Interruption of blood flow for only a few minutes may cause death of vital neurons and if interruption persists, all brain cells die in the affected area. The result is some degree of impairment of the body function that is controlled by the damaged region of the brain.
Myocardial Infarction / “Heart Attack” is the blockage of coronary blood vessels which disrupts coronary circulation. The heart muscles die from the lack of oxygen. The affected tissue then degenerates, creating a non-functional area (infarct). The heart ceases to be an effective pump i.e. it beats abnormally fast or produces an irregular heartbeat rhythm (ventricular fibrillation).
Embolism is a condition where a blood clot formed at an atherosclerotic site which break away and is carried around in the circulation. An embolus may then obstruct other small arteries.
Aneurysm is the dilation / bulge in the weakened wall of an artery; local dilation of an artery may rupture at any time.
7.3 Risk Factors for Heart Disease
7.3.1 Factors that can be modified, treat or control by changing lifestyle or taking medicine
7.3.1.1 Tobacco Smoke
Smokers’ risk of heart attack is more than twice that of non-smokers. Cigarette smoking is the biggest risk factor for sudden cardiac death. Smokers have 2 to 4 times the risk of non-smokers. Smokers who have a heart attack are also more likely to die and die suddenly within an hour. Smoking also acts with other risk factors to greatly increase the risk of coronary heart disease. People who smoke cigars or pipes seem to have a higher risk of death from coronary heart disease (and possibly stroke) but their risk isn’t as great as cigarette smokers. Constant exposure to other people’s smoke increases the risk of heart disease even for non-smokers.
7.3.1.2 High Blood Cholesterol
As blood cholesterol rises, so does risk of coronary heart disease. When other risk factors (such as high blood pressure and tobacco smoke) are present, this risk increases even more. A person’s cholesterol level is also affected by age, sex, heredity and diet.
7.3.1.3 High Blood Pressure
High blood pressure increases the heart’s workload, causing the heart to enlarge and weaken. It also increases the risk of stroke, heart attack, kidney failure and congestive heart failure. When high blood pressure exists with obesity, smoking, high blood cholesterol levels or diabetes, the risk of heart attack or stroke increases several times.
7.3.1.4 Physical Inactivity
An inactive lifestyle is a risk factor for coronary heart disease. Regular, moderate-to-vigorous physical activity helps prevent heart and blood vessel disease. The more vigorous the activity, the greater the benefits. However, even moderate-intensity activities help if done regularly and long term. Exercise can help control blood cholesterol, diabetes and obesity, as well as help lower blood pressure in some people.
7.3.1.5 Obesity and Overweight
People who have excess body fat, especially if a lot of it is in the waist, are more likely to develop heart disease and stroke even if they have no other risk factors. Excess weight increases the strain on the heart. It also raises the blood pressure, blood cholesterol and triglyceride levels and lowers HDL (good cholesterol) levels. It can also make diabetes more likely to develop. Many obese and overweight people may have difficulty losing weight. But by losing 10 to 20 pounds, it can help lower heart disease risk.
7.3.1.6 Diabetes Mellitus
Diabetes seriously increases the risk of developing cardiovascular disease. Even when glucose levels are under control, diabetes greatly increases the risk of heart disease and stroke. About 2/3 of people with diabetes die from some form of heart or blood vessel disease. It is important to work with a healthcare provider to manage diabetes and control any other risk factors.
7.3.2 Factors that cannot be changed
7.3.2.1 Increasing Age
About 4/5 of people who die of coronary heart disease are 65 or older. At older ages, women who have heart attacks are more likely than men are to die from them within a few weeks.
7.3.2.2 Male Gender
Men have a greater risk of heart attack then women do and they have attacks earlier in life. Even menopause, when women’s death rate from heart disease increases, it’s not as great as men’s.
7.3.2.3 Heredity (Including Race)
Children of parents with heart disease are more likely to develop it themselves. African Americans have more severe high blood pressure then Caucasians and a higher risk of heart disease. Heart disease risk is also higher among Mexican Americans, American Indians, native Hawaiians and some Asian Americans. This is partly due to higher rates of obesity and diabetes. Most people with a strong family history of heart disease have one or more other risk factors. Just as you cannot control your age, sex and race, you also cannot control your family history. It is even more important to treat and control any other risk factors you have.
7.3.3 Other Factors that contribute to heart disease
7.3.3.1 Stress
Individual response to stress may be a contributing factor. Some scientists have noted a relationship between coronary heart disease risk and stress in a person’s life, their health behaviours and socio-economic status. These factors may affect established risk factors. For example, people under stress may overeat, start smoking or smoke more than they otherwise would.
7.3.3.2 Alcohol
Drinking too much alcohol can raise blood pressure, cause heart failure and lead to a stroke. It can contribute to high triglycerides, cancer, other diseases and produce irregular heartbeats. It contributes to obesity, alcoholism, suicide and accidents.
8. Blood
8.1 Composition of Blood
There are plasma proteins (7%), other solutes (1%) and water (92%). All these are derived from the plasma which takes up 46-63% of the blood. The other 37-54% of blood is the formed elements. Of the formed elements, 0.1% are platelets and white blood cells. The other 99.9% are red blood cells.
8.2 Functions of Blood
The blood circulatory system is the internal communication system of the body by which a constant internal environment is maintained (homeostasis). Blood performs a number of functions, all concerned in one way or another with substance distribution regulation of blood levels of particular substances or body protection. These functions overlap and interact to maintain constancy of our internal environment.
8.2.1 Transportation
8.2.1.1 Respiratory Gases
It is involved with the delivery of dissolved gases such as oxygen from the lungs to all body cells and carbon dioxide from respiring tissues to the lungs.
8.2.1.2 Nutrients
It is also involved in the delivery of nutrients such as glucose, amino acids, fatty acids, electrolytes and water from the digestive tract to all body cells.
8.2.1.3 Excretory Materials
It is involved in the transporting metabolic waste products from cells to elimination sites. Water will be transported to the lungs and nitrogenous wastes (urea) to the kidneys. It also delivers certain toxic substances produced by pathogenic infection, physical damage to the liver (where they are destroyed) and to the kidneys (where they can be excreted).
8.2.2 Regulation
8.2.2.1 Hormones
They aid in transporting hormones (chemical messengers) from the endocrine organs to the target organs they regulate.
8.2.2.2 Temperature
In homeotherms, or warm-blooded vertebrates, a constant body temperature is maintained regardless of the ambient temperature. This is accomplished by absorbing and redistributing heat throughout the body and to the skin surface for dissipation of excess heat.
8.2.2.3 pH Regulation
Many blood proteins and other blood-borne solutes act as buffer to prevent excessive or abrupt changes in blood pH, to deal with acids generated by active tissues (lactic acid in skeletal muscles), which could jeopardize normal cellular activities. Blood acts as a reservoir for the body’s alkaline reserve of bicarbonate ions, hence normal blood is slightly alkaline with a pH between 7.35 and 7.45
8.2.2.4 Osmoregulation
It is tasked with maintaining adequate fluid volume and osmolarity in the circulatory system. It regulates the concentration of electrolytes (sodium and chloride ions) and blood proteins (albumin) and prevent excessive fluid loss from the bloodstream into the tissue spaces. It also provides a source of water for tissue cells and generates blood pressure to support efficient blood circulation to all parts of the body. It maintains osmotic concentration, hence the plasma osmotic pressure, which influences the movement of other solutes and water between blood and interstitial fluids.
8.2.3 Protection
8.2.3.1 Blood Clotting
This prevents excessive blood loss. When a blood vessel is damaged, fibrin and platelets initiate clot formation, halting excessive blood loss. It prevents drastic changes in blood volume that could seriously affect blood pressure and cardiovascular function.
8.2.3.2 Immune Defense
It prevents infection. Antibodies and complement proteins react and neutralize the harmful effects of foreign agents or toxins. Phagocytic white blood cells may recognize and ingest foreign invaders e.g. bacteria and viruses.
8.3 Erythrocytes / Red Blood Cells
The RBC is the most numerous type of cell in the blood. The average women have about 4.8 million RBCs per square cm and about 5.4 million for men. These values can fluctuate over a considerable range, depending on such factors as the individual’s health and the altitude at which the individual lives. Peruvians living at an altitude of 18 000 feet may have as many as 8.3 million RBCs per square cm.
Erythrocytes are disc-shaped with an average diameter of 7.5 microns and a thickness of 2 microns. The centre of the disc is thinner than the rim. The biconcave shape provides an increased surface area for gaseous diffusion, provides a shorter diffusion distance than a sphere and gives the erythrocyte greater flexibility to squeeze through marrow capillaries.
Discounting the water content, the RBC is 97% haemoglobin. RBCs lack mitochondria and generate ATP by anaerobic respiration.
When first formed in the bone marrow, erythrocytes have a nucleus and not very much haemoglobin. As they mature, the quantity of haemoglobin increases in the cell until it accounts for up to 90% of the dry weight of the cell. Toward the end of this process, the nucleus is squeezed out of the cell. It does not have many organelles, unable to carry out metabolic activities and also unable to reproduce by mitosis. It must rely on its store of already-produced proteins, enzymes and RNA to carry out vital energy-releasing processes but become progressively less active.
The life span of erythrocytes is about 120 days. Aged erythrocytes are ingested by phagocytic cells in the liver and spleen. Most of the iron of the haemoglobin is reclaimed for reuse. The remainder of the haem portion of the molecule is degraded into bile pigments and excreted by the liver. The iron portion is recycled for synthesis of new RBCs. Some 3 million RBCs die and are scavenged by the liver and spleen each second. The lost RBCs are normally replaced at the same rate or up to 4 times the rate of destruction by the bone marrow in a healthy adult.
8.4 Haemoglobin
Typically, the human body needs between 250 square cm (at rest) and 1000 square cm (in strenuous exercise) of oxygen per minute.
The oxygen is dissolved in 2 forms. It is dissolved in the blood plasma and erythrocyte plasma (2%). It is also reversibly combined with haemoglobin molecules (98%).
At body temperature, about 0.3 square cm of oxygen per minute can be dissolved in 100 square cm of blood plasma, but the total oxygen-carrying capacity of blood is about 20 square cm of oxygen per 100 square cm of blood. Thus, some 98% of oxygen is transported by haemoglobin.
An iron atom combines with a molecule of oxygen, but without oxidation of iron (II). The oxygen molecules fit into pockets in the haemoglobin called oxygen binding sites. Each haemoglobin molecule has 4 haem groups i.e. 4 iron atoms may carry up to 4 oxygen molecules. (Different haemoglobins found in animals have a different number of haem groups and so vary in their ability to carry oxygen.)
The reaction between haemoglobin and oxygen to form oxyhaemoglobin is reversible. Haemoglobin is contained in erythrocytes rather than in plasma to prevent it from breaking into fragments that would leak out of the bloodstream. Also, it is to prevent it from contributing to blood viscosity and osmotic pressure.
9. Transport of Oxygen
9.1 Oxygen Dissociation Curve
The oxygen-haemoglobin saturation / dissociation curve is a graph that relates the saturation of haemoglobin to the partial pressure of oxygen. The ODC was determined in normal blood with a pH of 7.4 and a temperature of 37 degree Celsius. The binding and dissociation of oxygen to haemoglobin is a typical reversible reaction.
Why is the ODC “S” shaped? At a greater partial pressure of oxygen, the haemoglobin becomes more saturated with oxygen. The extent to which the haemoglobin becomes saturated with oxygen is represented by an ODC. The curve is sigmoid shaped due to haem-haem effect. The oxygenation of 1 or the 4 haem groups greatly accelerates the oxygenation of the others (cooperativity). This haem-haem effect increases the rate and efficiency of oxygen uptake at respiratory membrane. The more the oxygen concentration, the higher the partial pressure of oxygen and thus the more saturated is the haemoglobin with oxygen.
9.1.1 Effect of pH, carbon dioxide and temperature
The quantity of oxygen transported by haemoglobin depends on pH as well as oxygen tension. In a more acidic environment, oxygen dissociates from the haemoglobin more readily i.e. the haemoglobin becomes less saturated. In a more alkaline environment, the association of oxygen with haemoglobin is favoured, forming more oxyhaemoglobin. As the pH decreases, the ODC moves to the right. This is called the Bohr Effect.
In addition to consuming oxygen, actively respiring tissues e.g. skeletal muscle releases a lot of carbon dioxide and generates acids such as carbonic acid and lactic acid (anaerobic respiration) that lower the pH of the interstitial fluid. Hydrogen ions produced can reduce haemoglobin by attaching to the same sites as oxygen atoms and thus they compete with oxygen for these sites.
The haemoglobin is acting as a pH buffer, keeping the blood pH at an optimum range between 7.2 to 7.6. A higher cellular metabolism increases the amount of oxygen required by the cell. By decreasing the affinity of haemoglobin with oxygen, these factors serve to allow more oxygen to be released by haemoglobin, thus more oxygen is made available to cells.
9.1.1.1 Implications / Significance of Bohr Effect
When Bohr Effect is operating, the Hb must be exposed to a higher partial pressure of oxygen to become fully saturated. But equally, it will release its oxygen at a higher partial pressure of oxygen. In other words, carbon dioxide makes the Hb less efficient at taking up oxygen, but more efficient at releasing it.
Actively respiring tissues release greater amounts of carbon dioxide or even accumulate lactic acid produced during anaerobic respiration. The Bohr shift brings a substantial decrease in the affinity of haemoglobin for oxygen.
If blood in the capillary beds of the tissue contains haemoglobin of reduced affinity, more oxygen will be unloaded from the pigment at the particular partial pressure of oxygen that prevails. Thus, the carbon dioxide released in respiring tissue accelerates the delivery of oxygen.
The net effect of the Bohr shift is that haemoglobin gives up a larger proportion of their bound oxygen than it would if carbon dioxide had no effect on the oxygen binding.
9.2 Foetal Haemoglobin vs. Adult Haemoglobin
The red blood cells of a developing foetus contain foetal haemoglobin. The structure of foetal Hb which differs from adult Hb in 2 of the 4 polypeptide chains, gives it a much higher affinity for oxygen. Therefore, at the same partial pressure of oxygen, foetal Hb will bind more oxygen than will adult Hb. This characteristic is important in transferring oxygen across the placenta. Although the foetus has its own lungs, it derives oxygen from the maternal bloodstream. The maternal blood which arrives at the placenta has relatively low partial pressure of oxygen, thus allowing the oxygen to diffuse into the foetal circulation. Because foetal Hb has a higher affinity for oxygen, it can still be 80% saturated with oxygen. the steep slope of the ODC means that it will release a large amount of oxygen in response to a very small change in partial pressure of oxygen between foetal blood and metabolically active foetal tissues. At birth, the production of foetal haemoglobin gives way to that of the adult type.
9.3 Haemoglobin vs. Myoglobin
Haemoglobin is in RBCs and myoglobin is in muscle cells. Myoglobin has a higher affinity for oxygen than haemoglobin. Both contain the oxygen-binding prosthetic group, haem.
Skeletal muscle of all vertebrates contains its own respiratory pigment, myoglobin (Mb). It consists of a single polypeptide chain and a single haem group. Mb is responsible for the colour of red muscles and is particularly abundant in active animals which are liable to suffer from oxygen shortage. There are very high levels of Mb in muscles of diving animals and in the flight muscles of birds.
Mb remains fully saturated with oxygen at partial pressures of oxygen well below that required for Hb to give up its oxygen. Mb stores oxygen, releasing it only when partial pressure of oxygen falls very low, as in severe muscular exertion. It delays the onset of anaerobic respiration.
In periods of extreme exertion, when the normal body supply of oxygen by blood is insufficient to keep pace with increased demand, the oxygen tension falls to a very low level. At these very low levels of partial pressure of oxygen, Mb releases its oxygen readily to keep the muscles working efficiently.
If muscular activity persists after the Mb-based oxygen supply is exhausted, then the muscle moves into a condition called oxygen debt, the muscle must respire by lactic acid fermentation.
Once exercise has ceased, the Mb oxygen store is replenished from the oxyhaemoglobin in the blood. The lactic acid that is accumulated is carried away to the liver for further metabolism (converted to pyruvate / glycogen).
The ODC of Mb is displaced left. Mb has an increased affinity for oxygen, stores oxygen at rest and releases oxygen when the partial pressure of oxygen is very low. It delays the onset of anaerobic respiration. Mb acts as an oxygen store. At normal partial pressures of oxygen in respiring muscles, Hb releases its oxygen. Some of this oxygen is picked up by Mb and held tightly. Mb does not release this oxygen unless the concentration of oxygen in muscle drops to a very low level i.e. unless the muscle is using up oxygen faster than Hb can supply it.
10. Transport of Carbon Dioxide
There are 3 methods of carrying carbon dioxide from the tissues to the respiratory surface.
10.1 Plasma Transport (dissolved carbon dioxide)
Plasma becomes saturated with carbon dioxide rapidly but only 7 to 10% of carbon dioxide produced by tissues is transported in this manner. Although carbon dioxide is more soluable in plasma than oxygen, its transport in blood plasma is still inadequate to meet the needs of most organisms.
10.2 Haemoglobin binding (carbaminohaemoglobin)
It accounts for the transport of 20-30% of carbon dioxide, which is chemically and reversibly bound to haemoglobin in RBCs. The reaction is rapid and does not require a catalyst. Carbon dioxide binds directly to the exposed amino groups of globin, not to the haem (usually erythrocytes which has released their oxygen to the tissues). Therefore, carbon dioxide transport does not compete with oxyhaemoglobin transport mechanism.
Carbon dioxide rapidly dissociates from Hb in the lungs, where partial pressure of carbon dioxide of the alveolar air is lower than that in blood. Carbon dioxide is loaded in the tissues, where partial pressure of carbon dioxide is higher than that of blood.
10.3 Carbonic Acid Formation (bicarbonate ions)
60-70% of carbon dioxide is transported this way. When carbon dioxide diffuses into the red blood cells, it combines with water, forming carbonic acid which is unstable and quickly dissociates into protons and bicarbonate ions.
Although this reaction also occurs in the plasma, it is much faster in the RBCs because they are rich in carbonic anhydrase, an enzyme that reversibly catalyses the conversion of water and carbon dioxide to carbonic acid.
The hydrogen ions released during the reaction bind to haemoglobin. The Hb molecules function as buffers, tying up the released hydrogen ions before the ions leave the RBCs and affect the plasma pH. By binding to Hb, it also triggers the Bohr Effect, thus oxygen release is enhanced.
The bicarbonate ions diffuse quickly from the RBCs into the plasma. The blood is slightly alkaline (pH 7.4) under normal conditions. It may also act as a buffer against hydrogen ions preventing the blood from becoming too acidic. Hence, blood becomes only slightly acidic as it passes through the tissues.
To counterbalance the rapid outflux of negatively charged bicarbonate ions from the RBCs, chloride ions move from the plasma into RBCs to maintain electrical neutrality. This ionic exchange is called chloride shift.
The membranes of the RBCs contain a sodium pump which pumps sodium ions out of these cells which associate with bicarbonate ions in the plasma to form sodium bicarbonate.