The circulatory system is one of the most well-known systems of the human body. It also forms part of the MCAT syllabus – within the Biological and Biochemical Foundations of Living Systems section – and therefore it’s essential that you have a good understanding of the circulatory system for the MCAT exam. This guide provides a comprehensive overview of the circulatory system to help you achieve a good MCAT score.
Originating at the heart and forming a complex system of arteries, veins and capillaries, the circulatory system is vital for the movement of nutrients, oxygen, hormones, and water amongst others around the body, delivering essential components for cellular processes and removing waste products from these very same processes. The human circulatory system is known as a ‘double circulatory system’ as the heart is split into two functional divisions: one pump which transports deoxygenated blood to the lungs to obtain oxygen, then back to the heart to the second pump, which transports this oxygenated blood to the rest of the body until it returns, deoxygenated, back to the first division.
The key functions of the circulatory system are:
The primary function of the circulatory system is responsible for exactly what it sounds like: circulation. Most nutrients are carried to different tissues through the blood, and similarly, oxygen is transported to tissues through the blood. Oxygen is carried in red blood cells: concave cells that lack a nucleus but contain hemoglobin, a 4-peptide molecule with the red-pigmented heme group that can bind several oxygen molecules and release them to tissues to allow for cellular respiration. Nutrients, hormones, and drugs, however, are carried in a variety of ways depending on their molecular composition. Globular molecules, with a hydrophobic core and hydrophilic outer layer, can travel freely in the blood. Other hydrophilic molecules can travel in the same way. The majority of molecules are transported bound to different proteins, the main one of these being albumin. This allows for polar, hydrophobic molecules to be carried in the hydrophilic environment of the blood. Along with every other organ system, the cardiovascular system has the ability to adapt to the body’s individual needs at that time. For instance, during exercise, capillaries at the skin surface will enlarge to allow for heat transfer out of the skin, the heartbeat will increase to allow for faster delivery and removal of blood constituents to cells, and blood flow will be focused on the essential organs to allow for optimum oxygen delivery.
The cardiovascular system also holds an important role in thermoregulation: the maintenance of a correct body temperature regardless of the external environment or pressures the body is put under, for instance, stress or exercise. The body needs to maintain a certain temperature (about 98°F) in order to allow for optimum function of different enzymes and bodily systems. The circulatory system allows for thermal energy to be transferred from the hot internal areas of the body to the external environment.
The basic structure of the heart consists of two atria (where blood empties into) and two ventricles (which pump the blood out of the heart).
Two veins deliver blood to the heart. The right side of the heart receives blood from the superior and inferior vena cava. The inferior vena cava drains blood from everywhere below the heart, from the abdomen downwards. The superior vena cava drains blood from anywhere above the heart, so the arms, neck, and head. The left side of the heart receives blood from the pulmonary vein, which carries oxygenated blood from the lungs to the heart.
The atria are smaller chambers which contain pectinate muscles: roughened ridges in the wall of the atria. The atria also have ‘appendages’, which are small areas in the atria that act as reserves for blood. Both of these physiological aspects of the atria, however, increase the risk of blood clots forming in the atria. For blood to pass into the ventricles, the atria must contract.
Blood travels through the atria to the ventricles through the atrioventricular valves: the tricuspid valve on the right side of the heart and the bicuspid (more commonly known as the mitral) valve on the left heart. These valves act to prevent backflow of blood into the atria when the ventricles contract. The function of the valves is dependent on muscles within the ventricles called the papillary muscles. These are finger-like muscular extensions from the ventricular wall, of which there are 3 in the right ventricle and 2 in the left ventricle, one for each valve. Connected to the papillary muscles are the fibrous chordae tendineae, which are in turn attached to the cusps of the valves. Ventricular contraction causes the chordae tendineae to pull the valves closed.
The ventricles are the biggest chambers in the heart, and their function is to pump the blood at a high enough pressure and velocity to allow it to travel around the body. They are heavily muscular, with the left ventricle having a thicker layer of muscle than the right ventricle. This is because the left ventricle has to pump blood further; it is traveling around the body instead of just to the lungs.
To exit the heart, blood is pumped through the semilunar valves. These are valves at the base of the arteries that leave the heart, which are the pulmonary artery in the right side and the aorta in the left side. The semilunar valves are the same on both sides and are forced open due to pressure within the heart. Similar to the atrioventricular valves, the purpose of the semilunar valves is to prevent the backflow of blood from the arteries back into the ventricles.
As previously mentioned, blood from the right side of the heart is deoxygenated, and passes to the pulmonary artery, which then branches into two and further divides to supply each part of the lung, following a similar pattern to the divisions of the bronchi as they extend into bronchioles. Blood from the left side of the heart, however, has arrived from the lungs through the pulmonary veins and must be delivered to the rest of the body as it is oxygenated. This blood leaves through a very large artery called the aorta, which gives off three main branches that supply the upper body before descending behind the heart down the abdomen and eventually splitting off into each leg to supply the lower limb.
Endothelial cells are the flat, thin cells that line blood vessels. They are responsible for releasing several factors, including nitrogen oxide for dilation of the vessels, ligands for blood clotting and receptors for different phagocytes. Depending on the type of blood vessel they are in, endothelial cells have different roles and therefore pathologies can affect them in different ways. In atherosclerosis, for instance, macrophages can invade the area underneath the endothelium in arteries, phagocytosing the smooth muscle layer and creating necrotic debris. The endothelium then becomes more fibrous as it hardens over time, reducing the elasticity of the arteries and narrowing the lumen. In capillaries, conversely, the endothelium is the layer across which different nutrients are transported to allow them to get into different tissues.
Blood pressure refers to the pressure that the blood exerts on arteries during different parts of the cardiac cycle. It is usually presented as a fraction, measured in millimeters of mercury (mmHg). The numerator refers to the pressure in blood vessels during ventricular systole, which is during ventricular contraction. This is the highest pressure that will exist in blood vessels. The denominator refers to the pressure in blood vessels during ventricular diastole, which is ventricular contraction. At this point in the cardiac cycle, the ventricles are filling and therefore no more blood is being pushed into the blood vessels, so the pressure is greatly reduced. This number refers to the minimum pressure within the blood vessels. The normal, standard blood pressure is 120/80mmHg. A blood pressure of under 90/60mmHg is hypotension (low blood pressure), whereas a reading of around 130/85mmHg or above is hypertension (high blood pressure).
Now you’re familiar with what you need to know about endothelial cells and blood pressure for the MCAT, you can start to explore blood vessels, and find out what information is required for the exam.
Blood vessels are divided into two main types: arteries and veins. They have three main layers: the tunica intima internally, which is an endothelial layer that faces the lumen and is responsible for producing factors to allow for vasodilation, blood clotting as well as having an immune function amongst others. The middle layer is the tunica media and is composed of primarily smooth muscle cells to allow for stretching of the blood vessels. The final layer, the external layer, is the tunica externa (or tunica adventitia), which is composed of collagenous connective tissue to prevent overexpansion of the blood vessels.
Arteries are thick vessels that carry mostly oxygenated blood from the heart around the body. The exception is the pulmonary artery, which carries deoxygenated blood to the lungs from the heart. They have a very small lumen, therefore the pressure in them is very high with a very fast flow rate, however, they can cope with this as the tunica media has a very thick layer of smooth muscle, allowing for them to expand and contract with each heartbeat, forcing the blood down around the systemic circulation. The largest artery in the human body is the aorta, with a diameter of about 2.5cm. Arteries branch off into arterioles, which are smaller arteries with a slightly wider lumen but still a large tunica intima: lumen ratio, especially in comparison to veins. These arterioles will further divide into capillaries, and then into venules as the blood becomes deoxygenated.
After the blood has passed through capillaries, it enters venules, which are small veins that, similar to arterioles, regulate the blood pressure so it does not overcome the type of vessel that it is in. Veins have a large lumen and a very thin smooth muscle layer, which means that the pressure within veins is a lot lower than that of arteries. This is a disadvantage as it is difficult for veins to force blood back up to the heart against gravity, making their flow rate also slower than that of arteries. However, they are adapted to overcome this. The majority of veins, except for spinal veins, contain valves to prevent the backflow of blood further down the veins. Furthermore, the thin wall of veins makes them easily compressible. Veins are usually accompanied by arteries, therefore the same pulsations that occur down arteries will compress the veins at different points and force blood back up to the heart. Most veins carry deoxygenated blood, with the exception of the pulmonary vein, which brings oxygenated blood from the lungs back to the heart.
The following are some key features of capillary beds which will be useful for your MCAT revision:
Capillaries are the smallest type of blood vessel, and they lack the normal 3 layers of every other type of blood vessel. Their wall is made up of a single cell layer of endothelium, which is adapted depending on the function of that type of capillary and what needs to pass through the membrane to the tissue. Continuous capillaries have no gaps in the membrane, so only non-polar molecules can pass through the membrane, for instance, oxygen. Fenestrated capillaries are capillaries with small gaps in the cell membrane. This allows for molecules such as glucose to pass through the membrane. The final type of capillaries are sinusoid capillaries that have both an incomplete cell membrane and an incomplete basement membrane. This allows for bigger molecules, like certain proteins and hormones, to pass across the cell membrane from the blood to the tissues and vice versa. Water is one of the only components of the blood that has specialized transport across the endothelium of the capillaries. This is done through specialized pores called aquaporins, which facilitate the movement of the polar water across the non-polar endothelial membrane. Filtration as a whole is much more common at the arteriolar end of the capillary instead of the venous end of the capillary. However, resorption of water is more common at the venous end of the capillary in order to prevent the buildup of fluid in the veins.
The capillaries are an important site of thermoregulation within the body. The human body releases thermal energy during respiration, which is increased during exercise, digestion and other bodily functions. The ability to maintain a correct body temperature is imperative as it allows for optimum function of enzymes and therefore cells within the body. The capillaries provide a rapid, constant flow of cool blood, therefore in cells that are rapidly respiring or are exposed to a hot environment, thermal energy can be transferred across the membranes to the capillaries. Capillary beds exist at several points within the body, but most notably at the skin and in the bronchi. When the body is high in thermal energy, the capillaries will expand and move closer to the surface of the skin and the bronchi, reducing the space between the capillary and the external environment, allowing for faster transfer of heat energy out. The opposite is true when it is too cold – the capillaries shrink away (vasoconstrict) from the surface of the skin so less thermal energy is lost through the skin.
Peripheral resistance is predominantly regulated through smaller arterioles instead of venules, due to the larger elastic potential that exists within the tunica media of the arterioles. Therefore, peripheral resistance is highest at these arterioles. It is important at this point to understand Poiseuille’s Law:
Where ∆P = difference in pressure gradient along the vessel
r = radius of the vessel
n = viscosity of fluid within the vessel
l = length of the vessel
8 signifies the velocity of flow
This equation, in simplistic terms, describes the fact that across a blood vessel, the pressure decreases as the viscosity of the blood also decreases. It can then be manipulated to work out resistance, where:
As the length of the vessel and viscosity of the fluid do not change much, this equation shows that the predominant regulator of resistance is the radius of the vessel. It can therefore be concluded that peripheral resistance is higher in arteries (as the radius of their lumen is smaller) than their comparative veins.
The following are the key areas covered in relation to the composition of blood on the MCAT syllabus, and therefore, essential for your MCAT revision:
The composition of the blood is split into three main parts: the plasma (55% of blood), red blood cells (41%) and white blood cells/platelets (4%). The plasma is responsible for carrying the majority of antibodies, hormones and nutrients in the bloodstream through different carrier proteins such as albumin, as well as having roles in changing the pH of the blood through the carbonic acid buffer in response to chemoreceptor activation and maintaining the osmotic gradient. The red blood cells are concave non-nucleated cells containing hemoglobin, which is responsible for carrying oxygen around the blood. White blood cells are split into several different groups; however, their collective role is in the immune response by tagging, targeting and breaking down pathogens that may find their way into the blood. Platelets are fragments of dead red blood cells that have a very important role in clotting blood.
The process of creating red blood cells, or erythrocytes, is known as erythropoiesis. It is stimulated by a hormone called erythropoietin, which is produced by the kidneys. The process of erythrocyte differentiation begins in the bone marrow with hematopoietic stem cells, which differentiate into reticulocytes (immature red blood cells) over a series of steps triggered by erythropoietin. These reticulocytes mature to form complete red blood cells, which have a life cycle of approximately 120 days. At the end of an erythrocyte’s life, it travels through the spleen and gets filtered out, which then gets phagocytosed.
The volume of the blood must be regulated for several reasons, including preventing cardiac overload and maintaining an optimum blood pressure. The main way in which this is done is through regulating the volume of plasma within the blood, through ‘oncotic pressure’, which is a type of pressure created by albumin and other proteins in the blood and their pull on fluids, mostly water, from the interstitial fluids back into the capillary. This is countered by hydrostatic pressure, which is the pressure exerted on the capillary walls by the fluids inside the capillary. Oncotic pressure is especially important in the venous system, where generally blood flow is slower and blood is more likely to ‘pool’ in the veins, resulting in an increase in hydrostatic pressure. In practice, this is most evident in the legs, as the effect of gravity results in more pooling of blood. In cases of diseases where there is a loss of protein within the blood, oncotic pressure decreases, therefore more fluid will leave the capillary (from increased hydrostatic pressure) while less fluid will be drawn back into the capillary (from decreased oncotic pressure). This results in a buildup of fluid within the legs, known as oedema.
The other way in which the plasma volume is maintained is through salts within the bloodstream. Sodium draws water into the bloodstream, therefore if an individual has a high proportion of salts within their blood, they are also likely to have an overload of plasma volume in the blood. The body has more management of this, through proteins called ‘natriuretic peptides’, which exist in the atria of the heart as ANPs and the ventricles of the heart as BNPs (brain natriuretic peptides). They are released in response to fluid overload, usually through stretching of the heart muscles. They are both responsible for decreasing the volume of plasma and act mainly at the kidneys, by preventing resorption of sodium into the blood (so decreasing water drawn back into the blood vessels) and decreasing levels of aldosterone, which in turn also decreases reabsorption of water from the kidneys.
Blood clots are clumps of ‘blood’ that are a mixture of clotting factors and platelets. They are useful when an individual has cut themselves to prevent bleeding and form a seal around a wound to prevent infection. The process of clotting starts with endothelial damage that results in a release of tissue factor. This triggers a series of steps of activating different clotting factors, which in turn activate other clotting factors until prothrombin is activated to thrombin and then fibrinogen is activated into fibrin. Fibrin then forms a fibril meshwork that works to trap red blood cells and platelets, thereby forming a mass that accumulates at the site of the injury. The process of this accumulation is due to interactions between platelets and the cut endothelium. There is an antigen on the platelets that binds to a receptor on the endothelium, and there is also an antigen on the endothelium that binds to the platelets, thereby causing the platelets trapped in the meshwork to bind to that area of the vessel, ensuring that the clot remains where it is meant to. Eventually, once the injured area is healed, plasminogen is converted to plasmin, which breaks down the clot.
Oxygen transport in the MCAT exam covers the following topics:
The majority of oxygen is transported in the bloodstream by hemoglobin, which is a 4-peptide structure that exists within the red blood cells. Each unit consists of 141-146 amino acids which are folded into globular proteins. The structure of each subunit consists of a peptide with a heme group attached to it. This heme group involves a central ion of iron, which is then surrounded by sodium ions and porphyrin, and this is where oxygen will bind. The subunits of hemoglobin can vary, with the adult hemoglobin consisting of 2 alpha and 2 beta chains, whereas fetal hemoglobin consists of 2 alpha and 2 gamma chains. Several hemoglobinopathies occur due to defects or changes in these chains, for instance alpha and beta thalassemia. As there are 4 subunits, each containing one heme group, each hemoglobin molecule can hold up to 4 oxygen molecules. In turn, each red blood cell carries about 250 million molecules of hemoglobin, making up 1/3 of their volume, therefore each red blood cell can carry up to 1 billion molecules of oxygen.
Oxygenation of the blood is measured in several different ways, and the implications of this are measured in several more ways too. In clinical practice, the standard way of finding the percentage of oxygenated hemoglobin in the blood is through pulse oximetry. This consists of a small machine being clipped onto one finger, that then finds the oxygenation of the blood. The other main way used in hospitals is an ABG, which is a sample of blood taken from the radial artery and is then examined to find levels of oxygen as well as carbon dioxide. Another important value, however, is hematocrit. This is a measure of the percentage of red blood cells in the blood volume, which should be about 40%. It can then be used to identify several types of diseases and is an indirect marker of oxygenation. The other potential marker is hemoglobin levels, which are often calculated alongside a hematocrit level. They are often measured in the raw number of hemoglobin molecules per red blood cell; therefore, defects can be identified.
Oxygen content in the blood is due to not only the binding of oxygen to hemoglobin, but also the amount of oxygen that is dissolved in the blood. Although most oxygen exists within hemoglobin, a small portion of it is soluble. However, the solubility of oxygen is inversely proportional to the temperature of the solution it is in. This means that warm-blooded mammals such as humans have a lower capability to dissolve oxygen than cold-blooded organisms.
Hemoglobin has varying levels of affinity for oxygen due to a theory called cooperative binding. This means that the lowest affinity of hemoglobin for oxygen is when no oxygen has bound to it, as the globular proteins in hemoglobin are at their Taut state (or T state). When oxygen binds to hemoglobin, it causes a conformational change in hemoglobin that opens it out to its Relaxed state (or R state). In this state, the hemoglobin proteins have opened out, making it easier for more molecules of oxygen to bind to hemoglobin until there are 4 oxygen molecules bound to it. This means that, until a certain point, an increased proportion of oxygen results in an increased saturation of hemoglobin, forming a sigmoid shaped curve. This phenomenon is more evident in fetuses, as they contain alpha and gamma chains instead of the alpha and beta chains that exist in adults. The gamma chain has a higher affinity for oxygen than the beta chains, as this means that the fetus’ oxygen needs are met even if the mother’s levels of oxygen are low.
Several factors influence this, including acidity (a lower pH shifts this curve to the right and vice versa), carbon dioxide levels (a lower level shifts the curve to the left), 2,3 DPG (a lower level shifts the curve to the left) and temperature (a lower temperature shifts the curve to the left).
Carbon dioxide can be carried in three ways, either through being dissolved in the blood, being bound to hemoglobin or, most commonly, existing as a polar bicarbonate ion. This occurs due to the action of carbonic anhydrase within a red blood cell and is a more efficient way of transporting carbon dioxide as it is more soluble. Bicarbonate can bind with hydrogen to then form carbonic acid, and bicarbonate can degenerate back to carbon dioxide in the lung capillaries. This allows for the carbon dioxide to diffuse across the alveolar membrane and exhale out. The normal level of carbon dioxide in the blood is 35-45mEq/l.
The heartbeat is regulated by a series of nodes within its walls that send electrical signals to initiate muscle contraction. The first of these is the sinoatrial node, located in the right atrium, and is responsible for initiating the contraction of the heartbeat. The cells involved in the sinoatrial node are capable of self-excitation, in which they do not require an external signal to initiate a response. The sinoatrial node sets the heartbeat at approximately 60-100 beats per minute, and the conduction velocity is about 0.5m/s.
Impulses from the sinoatrial node progress from the right atrium to the atrial septum, where the atrioventricular node arises. This node sends impulses down the septum that divides the right and left sides of the heart, triggering atrial contraction and therefore forcing blood into the ventricles. The AV node's natural impulse speed is 40-60BPM, and the conduction velocity is about 0.05m/s.
The next area of signal transduction through the heart contains the Bundle of His and exists in the ventricular septum. Impulses that travel down here assist at the end of atrial contraction and help to start ventricular contraction. Its natural impulse speed is 20BPM and the conduction velocity is 2 m/s.
The final important area holds the Purkinje fibers, which spread at the base of the septum, to the apex of the ventricles and then up around the lateral ventricles. The Purkinje fibers work to trigger ventricular contraction, forcing blood out of the heart and into the coronary vessels. The natural impulse speed is 20BPM and the conduction velocity is 4m/s.
All these areas work together to produce the heartbeat in the way we know it. However, as shown by the pattern of the speeds of impulses between each of the different areas, the sinoatrial node is the most important when it comes to maintaining the heartbeat. Normally, regardless of the natural impulse speeds of the nodes, the impulse speed they receive from the nodes before them overrides this. This means that even though the natural impulse speed of the Purkinje fibers is 20-40BPM, with a fully functioning sinoatrial node, they fire at 60-100BPM.
Thyroid hormone is a hormone released from the thyroid gland and activated to then have a role in the body. Although in normal concentrations, the thyroid can be beneficial, an increase or decrease in the quantity of thyroid hormone can be very detrimental and is very common. An overactive thyroid can cause a fast heart rate (tachycardia), known as chronotropy. It also increases inotropy, which is the strength of each individual heartbeat, increasing blood flow. Conversely, an underactive thyroid can cause a slow heart rate (bradycardia), as well as a decreased strength of each heartbeat.
Hopefully you’ll now have a good understanding of the circulatory system for the MCAT exam. If you’re looking for more MCAT resources to boost your revision, check out our MCAT blogs covering a whole range of MCAT syllabus key topics. You can also find everything you need to know about registering, preparing for and completing the MCAT exam in our MCAT Guide and our handy MCAT Checklist.