1 Section 1 Selected Diseases and Disorders of the Cardiovascular System

This chapter will cover the diseases and disorders associated with the Cardiovascular system. But before exploring what can go wrong let’s first review the cardiovascular anatomy and physiology.

The Heart

As you are all aware the heart is the organ that pumps blood throughout the body but how exactly does it work?

To begin, the heart has four chambers, two atria and two ventricles.  The atria and ventricles are separated into two sides (left and right) by the septum, a central wall of heart tissue that separates both the upper atria as well as the lower ventricles.  Horizontally, between the atria and ventricles are the atrioventricular valves which open as the heart fills and then close as the heart pumps blood out of the aorta and pulmonary arteries.  Oxygenated blood is pumped out of the left ventricle through the aorta to the rest of the body, called the systemic circuit. As the blood is distributed through the tissues it delivers oxygen and nutrients to cells and picks up carbon dioxide and waste. The blood then returns to the right side of the heart, where it is then pumped by the right ventricle into the pulmonary circuit where the blood is reoxygenated within the lungs. This cycle is repeating constantly at all times.  For adults, resting heart rate is approximately 60-100 beats per minute.

(Image of heart)

The heart wall is composed of three tissue layers; the endocardium, myocardium and epicardium. The innermost lining of the heart wall is the endocardium. The endocardium consists of simple squamous epithelial tissue that is continuous and integrated into all four valves. The central layer, the myocardium is composed of branching cardiac muscle cells (cardiomyocytes) which are arranged in parallel in a figure eight pattern around the atrioventricular valves.  The myocardium has a smooth outer surface and bumpy inner surface which are prominent with the ventricles and composed of trabeculae carneae.  The irregular branching ridges of the trabecula carneae is thought to facilitate both compression strength as well as reduce surface tension and suction during relaxation.  Note that the trabeculae carneae are present in the ventricles and are absent in the atria.  Within the atria, pectinate muscles, which are more prominent in the right atria than the left atria, are thought to have a similar function of the trabeculae carneae, in increasing strength and stability.  In comparison with the ventricles, the thinner walls of the atria are expected as the atria are required to generate less force than the ventricles.  Finally, the outermost layer of the heart is called the epicardium, also known as the visceral pericardium. The epicardium is made of simple squamous epithelium and secretes the serous fluid that is found within the pericardial cavity. The main function of the serous fluid is to protect the heart from rubbing on adjacent structures.

The pericardial cavity is created by the visceral pericardium folding back on itself, becoming the parietal pericardium, with the pericardial cavity in between these pericardial layers. The visceral and parietal pericardium are composed of simple squamous epithelial cells and are considered serous membranes, being able to produce and recycle pericardial fluid. This whole structure is called the pericardial sac. The outermost layer of the pericardial sac is called the fibrous pericardium. It is composed of dense, irregular connective tissue and is not expandable. The whole cavity that houses the heart, as well as portions of the esophagus and trachea, are in a central area of the upper thoracic cavity referred to as the mediastinum.

The valves

The heart contains four valves that prevent backflow of blood during the heartbeat. There are two types of valves present and each side of the heart has one of each. The atrioventricular (AV) valves are present between the atria and ventricles. The AV valve present on the left side of the heart is referred to as the bicuspid (or mitral) valve. The right AV valve is known as the tricuspid valve. The second type of valve is the semilunar valves which block the entrance between the heart and the major arteries (the aorta and pulmonary arteries). The two semilunar valves are referred to as the aortic and pulmonary which exist on the left and right sides, respectively at the entrance of the aorta and pulmonary trunk. The “lub dub” sound a heartbeat makes is due to turbulence of the blood caused by the opening and closing of these four valves.  The “lub” occurring when the AV valves close and the “dub” occurring when the semilunar valves close. Occasionally, the heart will make a third or fourth sound and this is called a murmur. It is often caused by an incompetent valve that isn’t closing properly, and the regurgitating blood creates a sound.  A second possible cause of an additional sound is a hole in the septum, most often caused by a congenital defect. This hole allows for blood to pass between ventricles making a sound during contraction that might be heard through a stethoscope.

Pulse

The pulse is often used to check heart rate. It feels like a throbbing of the blood vessels and moves in sync with the heart. The pulse can be observed in multiple points on the body as shown by the figure below.

(pulse location image)

Pulse deficit is a difference in the between the apical (bottom of heart) pulse and radial (wrist) pulse. These pulse rates should always be the same and thus a pulse deficit is a sign of abnormality. This usually occurs when the heartbeat isn’t strong enough for the ejected blood to reach the periphery vessels. This can be due to low stroke volume, the amount of blood exiting the heart per heart beat. If the stroke volume isn’t sufficient, the pressure wave won’t be strong enough to reach the extremities. The stroke volume can be low if there is poor filling or if the heart is too weak to contract sufficiently.

Conduction Pathways

The cardiac conduction pathway is responsible for the pace and synchronicity of the heartbeat. It begins with electrical activity in the Sinoatrial node (SA), an area of specialized cardiomyocytes that can spontaneously depolarize due to their leaky nature. The depolarization of the cells in the SA node starts and control the depolarization wave sent through the heart, and the SA node is therefore referred to as the pacemaker.  When depolarization occurs, the ions can spread quickly into the adjacent cardiomyocytes of the atria through gap junctions. These gap junctions allow for rapid transmission which is responsible for the synchronicity of atrial cell contraction. The depolarization wave will also travel down the internodal pathway, to arrive at the atrioventricular (AV) node. To visualize this, the SA node is in the roof of the right atrium and the AV node is in the floor of the right atrium. The AV node cells depolarize slightly slower, causing a slight pause which allows time for the atria to contract and push blood into the ventricles before the ventricles depolarize and then contract.  From the AV node, the depolarization wave will travel down the atrioventricular bundle (bundle of His), where it divides into the left and right bundle branches and then up the Purkinje fibres that run up the sides of each ventricle.  This allows for both ventricles to depolarized and then contract simultaneously.

At rest, there is a constant parasympathetic tone exerted on the SA node which keeps its depolarization rate at 60-80 times per minute.  Without this constant parasympathetic tone, the SA node would depolarize faster causing the heart to beat too fast.  Thus, it is heavily influenced by the parasympathetic nervous system, specifically through the Vagus nerve releasing acetylcholine on to cells of the SA node.  The AV node would be capable of keeping the heart beating at a proper rhythm without the influence of the SA node but if neither were functioning the heart would beat far too slow to sustain life.

To monitor the conduction of the heart, physicians use Electrocardiograms (ECG). These tests show a wave with components that correspond to each electrical event in a heartbeat.

(image of ECG wave)

The “P wave” is caused by the depolarization of the atria at the start of the heartbeat. Following is the “QRS complex” that corresponds to ventricular depolarization. Lastly, is the “T wave” which is present due to ventricular repolarization. These three components make up an electrical representation of a heartbeat. It should be noted that the atrial depolarization electrical event is hidden by the QRS wave.  The ECG is a non-invasive tool that can indicate any abnormalities in the cardiac conduction system. Any abnormal ECG patterns can be classified as an arrhythmia or a dysrhythmia. An arrhythmia is when the ECG shows a flat line meaning there is no heartbeat while a dysrhythmia is an abnormal wave. Abnormalities in heart conduction are often due to infarction caused by ischemia, lack of oxygen. The cells of the heart contain myoglobin, but don’t store oxygen for long as O2 is used rapidly.  Thus, any deprivation can cause cardiomyocytes to die.  Most often, reduction in oxygen levels are due to blocked coronary arteries.  Problems occurring in the rest of the body can cause issues in the cardiac conduction system as well. For example, electrolyte imbalance issues from improper diet, hydration levels, or kidney damage can affect the conduction system.

Tachycardia is a term used when the heart rate is too high, over 100 beats per minute. This is a problem because the heart doesn’t have enough time to refill between beats. Consequently, the stroke volume will decrease and the tissues won’t be adequately perfused. Bradycardia refers to a slow heart rate below 60 beats per minute. This condition can also lead to inadequate perfusion.

Factors controlling the Heart

There are two important baroreceptor sites, located in the aortic arch and carotid sinus. These specialized receptors are sensitive to the blood pressure in these vital blood vessels and send this information to the medulla oblongata. The medulla oblongata is the cardiovascular control center located in the brainstem that controls the heart rate, heart contractile strength, and level of blood vessel constriction (vasoconstriction).  A person’s blood pressure needs to be 120 mmHg (systolic) over 80 mmHg (diastolic) to provide sufficient blood flow to the vital organs.  The medulla oblongata is able to maintain this by adjusting heart rate, contractility and vasoconstriction.  Chemoreceptors also provide valuable information to the medulla oblongata about the pH, oxygen and carbon dioxide levels of both the blood and cerebrospinal fluid. Blood pH is ideally around 7.4, but can be altered by the amount of carbon dioxide present, as carbon dioxide is converted to carbonic acid.  For example, during exercise, skeletal muscle cells generate a lot of carbon dioxide, which can decrease blood pH.  The medulla oblongata responds by increasing heart rate and contractility which ensures blood is sent to the lungs where CO2 is expelled and blood is oxygenated and circulated more quickly.

To orchestrate responses to the needs of the body, signals from the baroreceptors and chemoreceptors are sent to the medulla oblongata, which then adjusts heart rate and contractility via the nervous system.  If the heart needs to increase its rate and contractility, a signal is sent down the Cardiac Accelerator Nerve which increases the firing of the SA node through releasing the neurotransmitter epinephrine.  Epinephrine binds receptors present on the SA node called beta-1-adrenergic receptors, which open calcium (Ca++) bringing cells closer to threshold, and therefore allowing for quicker depolarization events.  If the medulla oblongata senses that the heart needs to slow down then it sends an impulse down cranial nerve X, the Vagus nerve., which release acetylcholine, a neurotransmitter that opens more potassium (K+) channels, hyperpolarizing SA node cells so they are further from threshold and therefore slower to depolarize.

Temperature is another contributing factor to heart rate. Thermoregulation is the body’s way of maintaining proper temperature. When the body contains excess heat the cutaneous blood vessels dilate bringing more blood to the skin to release more heat, through radiation.  This increase in blood flow causes the reddening of skin during a warm day. This dilation of blood vessels requires the heart to beat faster to maintain adequate blood pressure. Exercise is another scenario in which the body, particularly the muscles, require increased vasodilation to supply of oxygen and nutrients. Increasing blood flow and blood pressure is achieved through the exposure of the SA node to epinephrine from the cardiac accelerator nerve causing an increase in force and contractility.

On another hand, smoking is another important factor that should be taken into consideration even though not everyone participates. There are five main problems associated with the cardiovascular system that can occur due to smoking. Firstly, smoking can cause an increase in the deposition of atherosclerotic plaque in blood vessels leading to peripheral artery disease. This narrowing of blood vessels can lead to lack of blood flow and thus lack of oxygen and nutrients to tissues. Secondly, smoking increases the risk of platelet clots that can lodge into circulatory beds that can cause Hypoxia, lack of oxygen. Thirdly, smoking causes the brain to release epinephrine which, as we know, speeds up the depolarization of the SA node increasing heart rate. Fourthly, while smoking you inhale Nicotine which is known to increase blood pressure in your blood vessels. Once you increase the peripheral blood pressure due to atherosclerotic plaque and the effects of nicotine, your heart must work harder to work against this pressure and continue pushing blood forward. This increased workload on the heart can lead to deterioration over time. Lastly, is the carbon monoxide released during smoking. Carbon monoxide is a poison that replaces oxygen by binding to hemoglobin, an oxygen carrier in the blood. In large quantities this can contribute to hypoxia in the tissues. When this occurs, chemoreceptors in your tissues send a message to the brain leading to an increased heart rate. The tar that builds up in the lungs due to smoking can inhibit gas exchange making it harder to get oxygen to the tissues and causing a similar reaction increasing the heart rate.

Pregnancy, due to growth, also affects heart rate by increasing the amount of blood vessels and tissues that the heart has to profuse. During pregnancy, again due to the growth involved of both mother and fetus, the basal metabolic rate (BMR) also increases as more anabolic (building) reactions are occurring in the body and more oxygen and ATP is therefore needed. This increased demand requires an increase in resting heart rate to deliver the increased capacity of nutrients and oxygen needed.

The Pathway of Blood

CO or Q are two abbreviations used to describe cardiac output. Cardiac output is defined as the amount of blood ejected from the ventricle in one minute. Stroke Volume is the volume that is ejected from the heart with each contraction sometimes known as ejection volume. To calculate cardiac output (mL/beat) stroke volume (mL) is multiplied by heart rate (bpm). Preload is the term for the volume of blood that enters the right atrium via venous return from the Inferior and Superior Vena Cava. Similarly, afterload is defined as the force required to eject blood from the left ventricle into the aorta. This definition explains why afterload is determined by peripheral resistance. To explain this concept further, imagine if the aorta was clenched, then it would be harder to push the blood through it. If the aorta was then released it would be easier to push the blood through it. A chronic increase in afterload can put a large strain on the heart overtime, particularly the left ventricular muscle. To clarify, the lower the afterload the easier it is for the left ventricle to pump blood out of the heart.

As previously mentioned, a healthy blood pressure is 120 mmHg systolic pressure and 80 mmHg diastolic pressure, and from that the mean arterial pressure is 93 mmHg. The mean arterial pressure is the pressure generated by the left ventricle. After leaving the heart, the blood pressure drops, as blood diverges into more and more arteriole branches. Blood pressure initially starts at 93 mmHg and drops to 35 mmHg by the time it reaches the capillaries. From the arteriole end of the capillary to the venous end of the capillary, the blood pressure further drops to 18 mmHg.  As blood travels back to the heart through the systemic veins, blood pressure drops further to 2 mmHg by the time it reaches the heart again. The cardiovascular system functions as a closed circuit which actually works really well for the body. It would be challenging to push blood back into the right atrium if it were at 93 mmHg pressure thus the low pressure inside the right atrium allow it to effectively refill. Once the blood enters the right atrium it proceeds to the right ventricle where it is then pumped to the pulmonary circuit by generating 12 mmHg of pressure. This pressure is sufficient as the pulmonary blood vessels are more distendable and the blood only has to travel through the lungs and back. This is the physiological reason the wall of the right ventricle is significantly thinner than the left, it doesn’t need to generate as much pressure.

Circling back, cardiac output is affected by heart rate and stroke volume. We covered that the sympathetic and parasympathetic branches of the nervous system can affect heart rate but what factors can affect stroke volume? For one, preload can influence the stroke volume and this refers to Sterling’s Law. Starling’s law states that if you increase end diastolic volume, meaning you increase the amount of blood entering your heart then you have to eject the same amount, increasing the stroke volume. The sympathetic nervous system can also work to increase stroke volume the same way it increases heart rate, by dumping epinephrine on the SA node. The epinephrine causes an increase in the strength of contraction and therefore the harder the heart squeezes the more blood that gets squeezed out. This is able to occur because the ventricles are never truly empty, there is always residual volume. Afterload negatively affects stroke volume because if the afterload is high then so is peripheral resistance meaning that stroke volume will decrease.

When blood is returning to the heart from the lower extremities it is going against gravity. Due to this force the body must have things that aid in the pathway of blood. The human body has three tools aiding in the journey of the blood against gravity. Firstly, there is the respiratory pump which is created by the change in pressure caused by breathing. As the chest expands during inspiration the pressure decreases which allows the blood to travel through the veins easier. Remember blood prefers travelling from an area of high pressure to low pressure. This process is similar to the process of sucking fluid through a straw. Secondly, the contraction of skeletal muscles can aid in pushing the blood up the veins and preventing backflow by putting pressure on the veins. Thirdly, there are valves that prevent blood from flowing backwards.

We’ve spoken about the systemic and pulmonary circuits but there is another small circuit to consider. The heart is a muscle that is beating all day, every day and thus requires a lot of oxygen and nutrients. The heart has its own circuit of blood vessels that supplies its needs branching off of the base of the aorta. These two arteries are called the Coronary arteries, specifically the left and right coronary arteries that supply the left and right side respectively. Since these arteries are embedded in the heart muscle they are more open during diastole, the state of relaxation of the heart. Once the heart contracts it squeezes these arteries so there is less flow through them. To reiterate, the base of the heart is the flatter surface that is closer to your head while the apex is the point that is pointing toward the feet. Anastomosis is defined as the connection between two branches of something, often arteries. Anastomosis near the apex of the heart illustrates collateral circulation, a backup blood supply for the heart. The heart doesn’t have the most efficient system for a backup blood supply and often if one artery gets clogged the collateral circulation is lost. An example scenario of this could be if a blood vessel contained an atherosclerotic plaque that is growing and limiting blood flow to an area of the heart, making it hypoxic. The cells in this area will begin releasing cytokines, which are chemicals that are released in states of physiological stress. These trigger the neighbouring artery to begin growing and it will extend into the affected area and become a collateral blood supply to keep the area alive and functional. This scenario could be detrimental to the cardiac conduction system if the right coronary artery was partially or fully occluded. In over 50% of people the right coronary artery supplies the SA node and in almost 100% of people it supplies the AV node. The loss of blood supply to these nodes would lead to conduction disturbances that could affect heart rate and the efficiency of the beat itself. The left coronary artery supplies the left side of the heart including the vital left ventricle that supplies blood to the systemic circulation. A blockage in this vessel could damage the heart muscle of the left ventricle leading to decreased stroke volume, cardiac output and consequently decreased blood flow to the remainder of the body. This issue is often leads to left-sided congestive heart failure. This state could lead to organ failure due to lack of oxygen and nutrients.

Blood Pressure

We’ve mentioned blood pressure briefly earlier in this chapter but now we are going to dive more in depth. Blood Pressure is defined as the amount of pressure exerted on the blood vessel walls by the blood. The blood pressure is highest when it exits the heart, so in the aorta. Remember, the average systolic blood pressure (during ventricular contraction) is 120 mmHg, the diastolic (between ventricular contraction) is 80 mmHg and the mean arterial pressure is 93 mmHg. As blood is dispersed through elastic vessels the pressure will start to decrease dropping to 2 mmHg by the time it reaches the Vena Cava. This system of high to low pressure is what allows blood to be pushed throughout the body. Blood pressure increases proportionally with the other factors affecting the blood such as cardiac output, stroke volume and resistance.

As we talked about, blood pressure has an optional range, so what happens when it is outside of the optimal range? People with high blood pressure, Hypertension, start to experience damage in their blood vessels. The increased pressure also increases the work the heart must do and this over a long period of time can lead to deterioration of the heart muscle. Medication can aid in lowering high blood pressure to prevent some of the damage if it is diagnosed. Unfortunately, high blood pressure doesn’t always present with signs or symptoms, therefore it is asymptomatic. Due to the asymptomatic nature of hypertension, people afflicted can go months or years without realising they have it allowing damage to occur unnoticed. Risk factors for hypertension are obesity, inactive lifestyle and diet low in fruits and vegetables.

If your blood pressure is too low, Hypotensive, there isn’t enough pressure to adequately push blood through the body and tissues become hypoxic and nutrient poor. Typically, your brain is going to give signs and symptoms first. If your brain is lacking in nutrients or oxygen you will begin to feel dizzy, faint, confused, irritable, anxious, fatigued, weak or experience blurry vision. Chemoreceptors and baroreceptors will notice the low oxygen and low pressure and notify the Medulla Oblongata, which will in turn speed up heart rate to try and compensate. This will increase the pressure but will create a problem if it is used as a long-term solution.

Another way the brain can act to ensure the proper tissues are getting adequate flow is to alter the diameter of blood vessels supplying a certain area. Vasoconstriction is where the diameter of blood vessels is decreased to divert blood away from an area that isn’t being actively used. For example, when you are exercising the blood vessels to your digestive organs will become vasoconstrict as you aren’t actively digesting as much as usual. Vasodilation is the opposite and is the increase in the diameter of a blood vessel to increase the flow of blood to a certain area. In the previous example the blood vessels supplying the skeletal muscles would dilate to provide more nutrients during exertion.

All three mechanisms your body has to ensure adequate blood flow, increased heart rate, increased stroke volume and vasoconstriction act to increase blood pressure. These mechanisms are all activated by the sympathetic nervous system. Epinephrine and Norepinephrine can bind two relevant receptors, Alpha -1- Adrenergic and Beta -1 adrenergic which lie in the arterial walls and the heart respectively.

To put it simply, if you increase sympathetic tone, then the arteries will vasoconstrict. This leads to more venous return as more blood is being pushed back to the heart and thus increasing blood pressure. A decrease in sympathetic tone will reverse this process leading to low blood pressure. If the blood pressure is low enough to set off the baroreceptors. As we know, baroreceptors can activate and deactivate the sympathetic nervous system to adjust blood pressure through the Medulla Oblongata but there is a second way.

Blood pressure is directly proportional to blood volume therefore it can be controlled via the kidneys. Your kidneys control your blood volume as they control the amount of urine that is excreted at any given time. Water that exits your body via the urine is filtered from your blood thus it affects blood volume directly. The kidneys are strongly influenced by hormones therefore so is blood volume and furthermore blood pressure. Firstly, Antidiuretic hormone (ADH) is released by the posterior pituitary gland. As its name predicts ADH reduces urination to retain blood volume. It can also act on the arterial walls causing vasoconstriction. Secondly, Aldosterone also helps control blood volume by reducing the excretion of water and salt in the form of urine, allowing water and salt to be retained in the blood. Thirdly, Renin is an enzyme that works alongside ADH and Aldosterone. Renin works to activate Angiotensin, a hormone that increases vasoconstriction. The active form, Angiotensin II is activated from angiotensin I via angiotensin converting enzyme (ACE) which is produced in the lungs. Angiotensin I is converted from Angiotensinogen by Renin. Angiotensin II also acts on the posterior pituitary gland to produce ADH and acts on the adrenal gland to produce more aldosterone. Lastly, erythropoietin is a hormone released by your kidney that stimulates the formation of new red blood cells.   More blood cells, just like more water and salt will increase blood volume and therefore blood pressure.

On the other hand, if blood pressure is too high, the atria will produce Atrial Natriuretic Peptide (ANP) which increases the excretion of salt and water into the urine to reduce blood volume and consequently blood pressure.

Inotropy

Beta -1- adrenergic receptors were mentioned above but there also happens to be Beta – 2- Adrenergic receptors that act similarly. When the sympathetic nervous system releases epinephrine/norepinephrine they bind the beta-1 and beta -2 receptors. This causes an adjustment of the calcium channels allowing them to depolarize faster. Iontropy refers to the speeding up conduction velocities of the conduction pathway that occurs through the sympathetic nervous system. This consequently also speeds up the depolarization and repolarization of the cell causing an increase in contractility. Beta Blockers act by blocking Beta-1-adrenergic receptors to avoid sympathetic stimulation of the heart thus preventing an increase in heart rate and contractility even if the brain is spending an impulse down the cardiac accelerator nerves. Beta blockers are used when the heart has been damaged and needs time to recover so it shouldn’t be working too hard. They also limit the amount of exercise a person can do as fatigue will occur quickly when the heart is unable to speed up. Acetylcholine, released by the parasympathetic nervous system, does the opposite of epinephrine and norepinephrine causing a decreased force of contractility and rate of depolarization and repolarization. Acetylcholine works by adjusting potassium channels and causing hyperpolarization. When a cell is hyperpolarized, it is slower to depolarize.