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The Cardiovascular System

Learn all about the heart, blood vessels, and composition of blood itself with our 3d models and explanations of cardiovascular system anatomy and physiology..

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The Cardiovascular System image

The cardiovascular system consists of the heart, blood vessels, and the approximately 5 liters of blood that the blood vessels transport. Responsible for transporting oxygen, nutrients, hormones, and cellular waste products throughout the body, the cardiovascular system is powered by the body’s hardest-working organ — the heart, which is only about the size of a closed fist. Even at rest, the average heart easily pumps over 5 liters of blood throughout the body every minute.mycontentbreak

Cardiovascular System Anatomy

The heart is a muscular pumping organ located medial to the lungs along the body’s midline in the thoracic region. The bottom tip of the heart, known as its apex, is turned to the left, so that about 2/3 of the heart is located on the body’s left side with the other 1/3 on right. The top of the heart, known as the heart’s base, connects to the great blood vessels of the body: the aorta , vena cava, pulmonary trunk, and pulmonary veins.

Circulatory Loops

There are 2 primary circulatory loops in the human body: the pulmonary circulation loop and the systemic circulation loop .

  • Pulmonary circulation transports deoxygenated blood from the right side of the heart to the lungs , where the blood picks up oxygen and returns to the left side of the heart. The pumping chambers of the heart that support the pulmonary circulation loop are the right atrium and right ventricle.
  • Systemic circulation carries highly oxygenated blood from the left side of the heart to all of the tissues of the body (with the exception of the heart and lungs). Systemic circulation removes wastes from body tissues and returns deoxygenated blood to the right side of the heart. The left atrium and left ventricle of the heart are the pumping chambers for the systemic circulation loop.

Blood Vessels

Blood vessels are the body’s highways that allow blood to flow quickly and efficiently from the heart to every region of the body and back again. The size of blood vessels corresponds with the amount of blood that passes through the vessel. All blood vessels contain a hollow area called the lumen through which blood is able to flow. Around the lumen is the wall of the vessel, which may be thin in the case of capillaries or very thick in the case of arteries.

All blood vessels are lined with a thin layer of simple squamous epithelium known as the endothelium that keeps blood cells inside of the blood vessels and prevents clots from forming. The endothelium lines the entire circulatory system, all the way to the interior of the heart, where it is called the endocardium.

There are three major types of blood vessels: arteries, capillaries and veins. Blood vessels are often named after either the region of the body through which they carry blood or for nearby structures. For example, the brachiocephalic artery carries blood into the brachial (arm) and cephalic (head) regions. One of its branches, the subclavian artery, runs under the clavicle; hence the name subclavian. The subclavian artery runs into the axillary region where it becomes known as the axillary artery.

Arteries and Arterioles

Arteries are blood vessels that carry blood away from the heart. Blood carried by arteries is usually highly oxygenated, having just left the lungs on its way to the body’s tissues. The pulmonary trunk and arteries of the pulmonary circulation loop provide an exception to this rule — these arteries carry deoxygenated blood from the heart to the lungs to be oxygenated.

Arteries face high levels of blood pressure as they carry blood being pushed from the heart under great force. To withstand this pressure, the walls of the arteries are thicker, more elastic, and more muscular than those of other vessels. The largest arteries of the body contain a high percentage of elastic tissue that allows them to stretch and accommodate the pressure of the heart.

Smaller arteries are more muscular in the structure of their walls. The smooth muscles of the arterial walls of these smaller arteries contract or expand to regulate the flow of blood through their lumen. In this way, the body controls how much blood flows to different parts of the body under varying circumstances. The regulation of blood flow also affects blood pressure, as smaller arteries give blood less area to flow through and therefore increases the pressure of the blood on arterial walls.

Arterioles are narrower arteries that branch off from the ends of arteries and carry blood to capillaries. They face much lower blood pressures than arteries due to their greater number, decreased blood volume, and distance from the direct pressure of the heart. Thus arteriole walls are much thinner than those of arteries. Arterioles, like arteries, are able to use smooth muscle to control their aperture and regulate blood flow and blood pressure.

Capillaries

Capillaries are the smallest and thinnest of the blood vessels in the body and also the most common. They can be found running throughout almost every tissue of the body and border the edges of the body’s avascular tissues. Capillaries connect to arterioles on one end and venules on the other.

Capillaries carry blood very close to the cells of the tissues of the body in order to exchange gases, nutrients, and waste products. The walls of capillaries consist of only a thin layer of endothelium so that there is the minimum amount of structure possible between the blood and the tissues. The endothelium acts as a filter to keep blood cells inside of the vessels while allowing liquids, dissolved gases, and other chemicals to diffuse along their concentration gradients into or out of tissues.

Precapillary sphincters are bands of smooth muscle found at the arteriole ends of capillaries. These sphincters regulate blood flow into the capillaries. Since there is a limited supply of blood, and not all tissues have the same energy and oxygen requirements, the precapillary sphincters reduce blood flow to inactive tissues and allow free flow into active tissues.

Veins and Venules

Veins are the large return vessels of the body and act as the blood return counterparts of arteries. Because the arteries, arterioles, and capillaries absorb most of the force of the heart’s contractions, veins and venules are subjected to very low blood pressures. This lack of pressure allows the walls of veins to be much thinner, less elastic, and less muscular than the walls of arteries.

Veins rely on gravity, inertia, and the force of skeletal muscle contractions to help push blood back to the heart. To facilitate the movement of blood, some veins contain many one-way valves that prevent blood from flowing away from the heart. As skeletal muscles in the body contract, they squeeze nearby veins and push blood through valves closer to the heart.

When the muscle relaxes, the valve traps the blood until another contraction pushes the blood closer to the heart. Venules are similar to arterioles as they are small vessels that connect capillaries, but unlike arterioles, venules connect to veins instead of arteries. Venules pick up blood from many capillaries and deposit it into larger veins for transport back to the heart.

Coronary Circulation

The heart has its own set of blood vessels that provide the myocardium with the oxygen and nutrients necessary to pump blood throughout the body. The left and right coronary arteries branch off from the aorta and provide blood to the left and right sides of the heart. The coronary sinus is a vein on the posterior side of the heart that returns deoxygenated blood from the myocardium to the vena cava.

Hepatic Portal Circulation

The veins of the stomach and intestines perform a unique function: instead of carrying blood directly back to the heart, they carry blood to the liver through the hepatic portal vein . Blood leaving the digestive organs is rich in nutrients and other chemicals absorbed from food. The liver removes toxins, stores sugars, and processes the products of digestion before they reach the other body tissues. Blood from the liver then returns to the heart through the inferior vena cava.

The average human body contains about 4 to 5 liters of blood. As a liquid connective tissue, it transports many substances through the body and helps to maintain homeostasis of nutrients, wastes, and gases. Blood is made up of red blood cells, white blood cells, platelets, and liquid plasma.

Red Blood Cells

Red blood cells, also known as erythrocytes, are by far the most common type of blood cell and make up about 45% of blood volume. Erythrocytes are produced inside of red bone marrow from stem cells at the astonishing rate of about 2 million cells every second. The shape of erythrocytes is biconcave—disks with a concave curve on both sides of the disk so that the center of an erythrocyte is its thinnest part. The unique shape of erythrocytes gives these cells a high surface area to volume ratio and allows them to fold to fit into thin capillaries. Immature erythrocytes have a nucleus that is ejected from the cell when it reaches maturity to provide it with its unique shape and flexibility. The lack of a nucleus means that red blood cells contain no DNA and are not able to repair themselves once damaged.

Erythrocytes transport oxygen in the blood through the red pigment hemoglobin. Hemoglobin contains iron and proteins joined to greatly increase the oxygen carrying capacity of erythrocytes. The high surface area to volume ratio of erythrocytes allows oxygen to be easily transferred into the cell in the lungs and out of the cell in the capillaries of the systemic tissues.

White Blood Cells

White blood cells, also known as leukocytes, make up a very small percentage of the total number of cells in the bloodstream, but have important functions in the body’s immune system . There are two major classes of white blood cells: granular leukocytes and agranular leukocytes.

  • Granular Leukocytes: The three types of granular leukocytes are neutrophils, eosinophils, and basophils. Each type of granular leukocyte is classified by the presence of chemical-filled vesicles in their cytoplasm that give them their function. Neutrophils contain digestive enzymes that neutralize bacteria that invade the body. Eosinophils contain digestive enzymes specialized for digesting viruses that have been bound to by antibodies in the blood. Basophils release histamine to intensify allergic reactions and help protect the body from parasites.
  • Agranular Leukocytes: The two major classes of agranular leukocytes are lymphocytes and monocytes. Lymphocytes include T cells and natural killer cells that fight off viral infections and B cells that produce antibodies against infections by pathogens. Monocytes develop into cells called macrophages that engulf and ingest pathogens and the dead cells from wounds or infections.

Also known as thrombocytes, platelets are small cell fragments responsible for the clotting of blood and the formation of scabs. Platelets form in the red bone marrow from large megakaryocyte cells that periodically rupture and release thousands of pieces of membrane that become the platelets. Platelets do not contain a nucleus and only survive in the body for up to a week before macrophages capture and digest them.

Plasma is the non-cellular or liquid portion of the blood that makes up about 55% of the blood’s volume. Plasma is a mixture of water, proteins, and dissolved substances. Around 90% of plasma is made of water , although the exact percentage varies depending upon the hydration levels of the individual. The proteins within plasma include antibodies and albumins. Antibodies are part of the immune system and bind to antigens on the surface of pathogens that infect the body. Albumins help maintain the body’s osmotic balance by providing an isotonic solution for the cells of the body. Many different substances can be found dissolved in the plasma, including glucose, oxygen, carbon dioxide, electrolytes, nutrients, and cellular waste products. The plasma functions as a transportation medium for these substances as they move throughout the body.

Cardiovascular System Physiology

Functions of the cardiovascular system.

The cardiovascular system has three major functions: transportation of materials, protection from pathogens, and regulation of the body’s homeostasis.

  • Transportation : The cardiovascular system transports blood to almost all of the body’s tissues. The blood delivers essential nutrients and oxygen and removes wastes and carbon dioxide to be processed or removed from the body. Hormones are transported throughout the body via the blood’s liquid plasma.
  • Protection : The cardiovascular system protects the body through its white blood cells. White blood cells clean up cellular debris and fight pathogens that have entered the body. Platelets and red blood cells form scabs to seal wounds and prevent pathogens from entering the body and liquids from leaking out. Blood also carries antibodies that provide specific immunity to pathogens that the body has previously been exposed to or has been vaccinated against.
  • Regulation : The cardiovascular system is instrumental in the body’s ability to maintain homeostatic control of several internal conditions. Blood vessels help maintain a stable body temperature by controlling the blood flow to the surface of the skin . Blood vessels near the skin’s surface open during times of overheating to allow hot blood to dump its heat into the body’s surroundings. In the case of hypothermia, these blood vessels constrict to keep blood flowing only to vital organs in the body’s core. Blood also helps balance the body’s pH due to the presence of bicarbonate ions, which act as a buffer solution. Finally, the albumins in blood plasma help to balance the osmotic concentration of the body’s cells by maintaining an isotonic environment.

Many serious conditions and diseases can cause our cardiovascular system to stop working properly. Quite often, we don’t do enough about them proactively, resulting in emergencies. Browse our content to learn more about cardiovascular health . Also, explore how DNA health testing can allow you to begin important conversations with your doctor about genetic risks for disorders involving clotting, hemophilia, hemochromatosis (a common hereditary disorder causing iron to accumulate in the heart) and glucose-6-phosphate dehydrogenase (which affects about 1 in 10 African American men).

The Circulatory Pump

The heart is a four-chambered “double pump,” where each side (left and right) operates as a separate pump. The left and right sides of the heart are separated by a muscular wall of tissue known as the septum of the heart. The right side of the heart receives deoxygenated blood from the systemic veins and pumps it to the lungs for oxygenation. The left side of the heart receives oxygenated blood from the lungs and pumps it through the systemic arteries to the tissues of the body. Each heartbeat results in the simultaneous pumping of both sides of the heart, making the heart a very efficient pump.

Regulation of Blood Pressure

Several functions of the cardiovascular system can control blood pressure. Certain hormones along with autonomic nerve signals from the brain affect the rate and strength of heart contractions. Greater contractile force and heart rate lead to an increase in blood pressure. Blood vessels can also affect blood pressure. Vasoconstriction decreases the diameter of an artery by contracting the smooth muscle in the arterial wall. The sympathetic (fight or flight) division of the autonomic nervous system causes vasoconstriction, which leads to increases in blood pressure and decreases in blood flow in the constricted region. Vasodilation is the expansion of an artery as the smooth muscle in the arterial wall relaxes after the fight-or-flight response wears off or under the effect of certain hormones or chemicals in the blood. The volume of blood in the body also affects blood pressure. A higher volume of blood in the body raises blood pressure by increasing the amount of blood pumped by each heartbeat. Thicker, more viscous blood from clotting disorders can also raise blood pressure.

Hemostasis, or the clotting of blood and formation of scabs, is managed by the platelets of the blood. Platelets normally remain inactive in the blood until they reach damaged tissue or leak out of the blood vessels through a wound. Once active, platelets change into a spiny ball shape and become very sticky in order to latch on to damaged tissues. Platelets next release chemical clotting factors and begin to produce the protein fibrin to act as structure for the blood clot. Platelets also begin sticking together to form a platelet plug. The platelet plug will serve as a temporary seal to keep blood in the vessel and foreign material out of the vessel until the cells of the blood vessel can repair the damage to the vessel wall.

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Biology LibreTexts

17.2: Introduction to the Cardiovascular System

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  • Page ID 16824

  • Suzanne Wakim & Mandeep Grewal
  • Butte College

Ant Hill or Plumbing System?

What do you think Figure \(\PageIndex{1}\) shows? Does it show a maze of underground passageways in an anthill? A network of interconnected pipes in a complex plumbing system? The picture actually shows something that, like ant tunnels and plumbing pipes, functions as a transportation system. It shows a network of blood vessels. Blood vessels are part of the cardiovascular system.

ant hill tunnels

What is the Cardiovascular System?

The cardiovascular system , also called the circulatory system, is the organ system that transports materials to and from all the cells of the body. The materials carried by the cardiovascular system include oxygen from the lungs, nutrients from the digestive system, hormones from glands of the endocrine system, and waste materials from cells throughout the body. Transport of these and many other materials is necessary to maintain homeostasis of the body. The main components of the cardiovascular system are the heart, blood vessels, and blood. Each of these components is shown in Figure \(\PageIndex{2}\) and introduced in the text.

Circulatory System no tags

The heart is a muscular organ in the chest. It consists mainly of cardiac muscle tissue and pumps blood through blood vessels by repeated, rhythmic contractions. As shown in Figure \(\PageIndex{3}\), the heart has four inner chambers: a right atrium and ventricle and a left atrium and ventricle. On each side of the heart, blood is pumped from the atrium to the ventricle below it and from the ventricle out of the heart. The heart also contains several valves that allow blood to flow only in the proper direction through the heart.

Heart Anatomy

Unlike skeletal muscle, cardiac muscle routinely contracts without stimulation by the nervous system. Specialized cardiac muscle cells send out electrical impulses that stimulate the contractions. As a result, the atria and ventricles normally contract with just the right timing to keep blood pumping efficiently through the heart.

Blood Vessels

types of blood vessels

The blood vessels of the cardiovascular system are like a network of interconnected, one-way roads that range from superhighways to back alleys. Like a network of roads, the blood vessels have the job of allowing the transport of materials from one place to another. There are three major types of blood vessels: arteries, veins, and capillaries. They are illustrated in Figure \(\PageIndex{4}\).

  • Arteries are blood vessels that carry blood away from the heart (except for the arteries that actually supply blood to the heart muscle). Most arteries carry oxygen-rich blood, and one of their main functions is distributing oxygen to tissues throughout the body. The smallest arteries are called arterioles.
  • Veins are blood vessels that carry blood toward the heart. Most veins carry deoxygenated blood. The smallest veins are called venules.
  • Capillaries are the smallest blood vessels. They connect arterioles and venules. As they pass through tissues, they exchange substances including oxygen with cells.

Two Circulations

Cells throughout the body need a constant supply of oxygen. They get oxygen from capillaries in the systemic circulation. The systemic circulation is just one of two interconnected circulations that make up the human cardiovascular system. The other circulation is the pulmonary system. This is where the blood picks up oxygen to carry to cells. It takes blood about 20 seconds to make one complete transit through both circulations.

Pulmonary Circulation

The pulmonary circulation involves only the heart and lungs and the major blood vessels that connect them. It is illustrated in Figure \(\PageIndex{5}\). Blood moves through the pulmonary circulation from the heart to the lungs, and back to the heart again, becoming oxygenated in the process. Specifically, the right ventricle of the heart pumps deoxygenated blood into the right and left pulmonary arteries. These arteries carry the blood to the right and left lungs, respectively. Oxygenated blood then returns from the right and left lungs through the two right and two left pulmonary veins. All four pulmonary veins enter the left atrium of the heart.

pulmonary circuit

What happens to the blood while it is in the lungs? It passes through increasingly smaller arteries and finally through capillary networks surrounding the alveoli (Figure \(\PageIndex{6}\)). This is where gas exchange takes place. The deoxygenated blood in the capillaries picks up oxygen from the alveoli and gives up carbon dioxide to the alveoli. As a result, the blood returning to the heart in the pulmonary veins is almost completely saturated with oxygen.

Pulmonary Blood Circulation

Systemic Circulation

The oxygenated blood that enters the left atrium of the heart in the pulmonary circulation then passes into the systemic circulation. This is the part of the cardiovascular system that transports blood to and from all of the tissues of the body to provide oxygen and nutrients and pick up wastes. It consists of the heart and blood vessels that supply the metabolic needs of all the cells in the body, including those of the heart and lungs.

heart systemic circulation

As shown in Figure \(\PageIndex{7}\), in the systemic circulation, the left atrium pumps oxygenated blood to the left ventricle, which pumps the blood directly into the aorta, the body’s largest artery. Major arteries branching off the aorta carry the blood to the head and upper extremities. The aorta continues down through the abdomen and carries blood to the abdomen and lower extremities. The blood then returns to the heart through the network of increasingly larger veins of the systemic circulation. All of the returning blood eventually collects in the superior vena cava (upper body) and inferior vena cava (lower body), which empty directly into the right atrium of the heart.

Blood is a fluid connective tissue that circulates throughout the body in blood vessels by the pumping action of the heart. Blood carries oxygen and nutrients to all the body’s cells, and it carries carbon dioxide and other wastes away from the cells to be excreted. Blood also transports many other substances, defends the body against infection, repairs body tissues, and controls the body’s pH, among other functions.

The fluid part of blood is called plasma. It is a yellowish, watery liquid that contains many dissolved substances and blood cells. Types of blood cells in plasma include red blood cells, white blood cells, and platelets, all of which are illustrated in Figure \(\PageIndex{8}\) and explained in the text.

Red White Blood cells

  • Red blood cells have the main function of carrying oxygen in the blood. Red blood cells consist mostly of hemoglobin, a protein containing iron that binds with oxygen.
  • White blood cells are far fewer in number than red blood cells. They defend the body in various ways. For example, white blood cells called phagocytes swallow and destroy pathogens, dead cells, and other debris in the blood.
  • Platelets are cell fragments involved in blood clotting. They stick to tears in blood vessels and to each other, forming a plug at the site of injury. They also release chemicals that are needed for clotting to occur.
  • What is the cardiovascular system? What are its main components?
  • Describe the heart and how it functions.
  • List the three major types of blood vessels and their basic functions.
  • Compare and contrast the pulmonary and systemic circulations.
  • What is blood? What are its chief constituents?
  • True or False. The circulatory system brings blood to and from the body, while the cardiovascular system brings blood to and from the lungs only.
  • True or False. Arteries carry mainly oxygenated blood.
  • Name three different types of substances that are transported by the cardiovascular system.
  • Describe where and how the pulmonary and systemic circulation systems meet.

A. Left pulmonary artery

B. Left pulmonary vein

C. Right pulmonary artery

D. Right pulmonary vein

capillaries; venules; aorta; veins; arteries

  • Explain why the heart and lungs need blood from the systemic circulation.
  • Choose one. Blood vessels carrying deoxygenated blood from the body back to the heart get increasingly (larger/smaller).

A. Arterioles

B. Capillaries

D. Bronchioles

  • Which type of blood cell carries oxygen?

Explore More

Watch this fun and fast-paced CrashCourse video to explore how the cardiovascular and respiratory systems work together to deliver oxygen and remove carbon dioxide from cells.

Check out this video to learn more about how the heart pumps blood:

Attributions

  • Blood Vessels by Jiulin Du from CK-12 licensed CC BY-NC 3.0
  • Circulatory System by Mariana Ruiz Villarreal ( LadyofHats ), public domain via Wikimedia Commons
  • Heart Anatomy by Blausen.com staff (2014). " Medical gallery of Blausen Medical 2014 ". WikiJournal of Medicine 1 (2). DOI : 10.15347/wjm/2014.010 . ISSN 2002-4436 . licensed CC BY 3.0 via Wikimedia Commons
  • Blood Vessels by Rupali Raju from CK-12 licensed CC BY-NC 3.0
  • Pulmonary circuit by Arcadian public domain via Wikimedia Commons
  • Pulmonary blood circulation by Holly Fisher, CC BY 3.0 via Wikimedia Commons
  • Systemic Circuit by US Government, public domain via Wikimedia Commons
  • Red White Blood Cells by Electron Microscopy Facility at The National Cancer Institute at Frederick (NCI-Frederick), public domain via Wikimedia Commons
  • Text adapted from Human Biology by CK-12 licensed CC BY-NC 3.0

Cardiovascular System Anatomy and Physiology

Cardiovascular System Anatomy and Physiology Nursing Study Guide

Journey to the heart of our being with the cardiovascular system study guide . Aspiring nurses, chart the pulsating rivers of life as you discover the anatomy and dynamics of the body’s powerful pump and intricate vessel networks.

Table of Contents

Functions of the heart, heart structure and functions, layers of the heart, chambers of the heart, associated great vessels, heart valves, cardiac circulation vessels, blood vessels, major arteries of the systemic circulation, major veins of the systemic circulation, intrinsic conduction system of the heart, the pathway of the conduction system, cardiac cycle and heart sounds, cardiac output, physiology of circulation, cardiovascular vital signs, blood circulation through the heart, capillary exchange of gases and nutrients, age-related physiological changes in the cardiovascular system.

The functions of the heart are as follows:

  • Managing blood supply. Variations in the rate and force of heart contraction match blood flow to the changing metabolic needs of the tissues during rest, exercise, and changes in body position.
  • Producing blood pressure. Contractions of the heart produce blood pressure, which is needed for blood flow through the blood vessels.
  • Securing one-way blood flow. The valves of the heart secure a one-way blood flow through the heart and blood vessels.
  • Transmitting blood. The heart separates the pulmonary and systemic circulations, which ensures the flow of oxygenated blood to tissues.

Anatomy of the Heart

The cardiovascular system can be compared to a muscular pump equipped with one-way valves and a system of large and small plumbing tubes within which the blood travels.

The modest size and weight of the heart give few hints of its incredible strength.

Heart Anatomy - Anatomy and Physiology

  • Weight. Approximately the size of a person’s fist, the hollow , cone-shaped heart weighs less than a pound .
  • Mediastinum. Snugly enclosed within the inferior mediastinum, the medial cavity of the thorax, the heart is flanked on each side by the lungs.
  • Apex. Its more pointed apex is directed toward the left hip and rests on the diaphragm, approximately at the level of the fifth intercostal space.
  • Base. Its broad posterosuperior aspect, or base , from which the great vessels of the body emerge, points toward the right shoulder and lies beneath the second rib.
  • Pericardium. The heart is enclosed in a double-walled sac called the pericardium which is the outermost layer of the heart.
  • Fibrous pericardium. The loosely fitting superficial part of this sac is referred to as the fibrous pericardium, which helps protect the heart and anchors it to surrounding structures such as the diaphragm and sternum .
  • Serous pericardium. Deep to the fibrous pericardium is the slippery, two-layer serous pericardium, where its parietal layer lines the interior of the fibrous pericardium.

The heart muscle has three layers and they are as follows:

  • Epicardium. The epicardium or the visceral and outermost layer is actually a part of the heart wall.
  • Myocardium. The myocardium consists of thick bundles of cardiac muscle twisted and whirled into ringlike arrangements and it is the layer that actually contracts.
  • Endocardium. The endocardium is the innermost layer of the heart and is a thin, glistening sheet of endothelium hat lines the heart chambers.

The heart has four hollow chambers, or cavities: two atria and two ventricles.

  • Receiving chambers. The two superior atria are primarily the receiving chambers, they play a lighter role in the pumping activity of the heart.
  • Discharging chambers. The two inferior, thick-walled ventricles are the discharging chambers, or actual pumps of the heart wherein when they contract, blood is propelled out of the heart and into circulation.
  • Septum. The septum that divides the heart longitudinally is referred to as either the interventricular septum or the interatrial septum, depending on which chamber it separates.

The great blood vessels provide a pathway for the entire cardiac circulation to proceed.

  • Superior and inferior vena cava. The heart receives relatively oxygen-poor blood from the veins of the body through the large superior and inferior vena cava and pumps it through the pulmonary trunk .
  • Pulmonary arteries. The pulmonary trunk splits into the right and left pulmonary arteries, which carry blood to the lungs, where oxygen is picked up and carbon dioxide is unloaded.
  • Pulmonary veins. Oxygen-rich blood drains from the lungs and is returned to the left side of the heart through the four pulmonary veins.
  • Aorta. Blood returned to the left side of the heart is pumped out of the heart into the aorta from which the systemic arteries branch to supply essentially all body tissues.

The heart is equipped with four valves, which allow blood to flow in only one direction through the heart chambers.

presentation cardiovascular system

  • Atrioventricular valves. Atrioventricular or AV valves are located between the atrial and ventricular chambers on each side, and they prevent backflow into the atria when the ventricles contract.
  • Bicuspid valves. The left AV valve- the bicuspid or mitral valve, consists of two flaps, or cusps, of the endocardium.
  • Tricuspid valve. The right AV valve, the tricuspid valve, has three flaps.
  • Semilunar valve. The second set of valves, the semilunar valves, guards the bases of the two large arteries leaving the ventricular chambers, thus they are known as the pulmonary and aortic semilunar valves.

Although the heart chambers are bathed with blood almost continuously, the blood contained in the heart does not nourish the myocardium.

  • Coronary arteries. The coronary arteries branch from the base of the aorta and encircle the heart in the coronary sulcus (atrioventricular groove) at the junction of the atria and ventricles, and these arteries are compressed when the ventricles are contract and fill when the heart is relaxed.
  • Cardiac veins. The myocardium is drained by several cardiac veins, which empty into an enlarged vessel on the posterior of the heart called the coronary sinus .

Blood circulates inside the blood vessels, which form a closed transport system, the so-called vascular system.

  • Arteries. As the heart beats, blood is propelled into large arteries leaving the heart.
  • Arterioles. It then moves into successively smaller and smaller arteries and then into arterioles, which feed the capillary beds in the tissues.
  • Veins. Capillary beds are drained by venules , which in turn empty into veins that finally empty into the great veins entering the heart.

Except for the microscopic capillaries, the walls of the blood vessels have three coats or tunics.

presentation cardiovascular system

  • Tunica intima. The tunica intima, which lines the lumen, or interior, of the vessels, is a thin layer of endothelium resting on a basement membrane and decreases friction as blood flows through the vessel lumen.
  • Tunica media. The tunica media is the bulky middle coat which mostly consists of smooth muscle and elastic fibers that constrict or dilate, making the blood pressure increase or decrease.
  • Tunica externa. The tunica externa is the outermost tunic composed largely of fibrous connective tissue, and its function is basically to support and protect the vessels.

The major branches of the aorta and the organs they serve are listed next in the sequence from the heart.

presentation cardiovascular system

Arterial Branches of the Ascending Aorta

The aorta springs upward from the left ventricle of the heart as the ascending aorta.

  • Coronary arteries. The only branches of the ascending aorta are the right and left coronary arteries, which serve the heart.

Arterial Branches of the Aortic Arch

The aorta arches to the left as the aortic arch.

  • Brachiocephalic trunk. The brachiocephalic trunk, the first branch off the aortic arch, splits into the right common carotid artery and right subclavian artery .
  • Left common carotid artery. The left common carotid artery is the second branch of the aortic arch and it divides, forming the left internal carotid , which serves the brain, and the l eft external carotid , which serves the skin and muscles of the head and neck.
  • Left subclavian artery. The third branch of the aortic arch, the left subclavian artery , gives off an important branch- the vertebral artery , which serves as part of the brain.
  • Axillary artery. In the axilla, the subclavian artery becomes the axillary artery.
  • Brachial artery. the subclavian artery continues into the arm as the brachial artery, which supplies the arm.
  • Radial and ulnar arteries. At the elbow, the brachial artery splits to form the radial and ulnar arteries, which serve the forearm.

Arterial Branches of the Thoracic Aorta

The aorta plunges downward through the thorax, following the spine as the thoracic aorta.

  • Intercostal arteries. Ten pairs of intercostal arteries supply the muscles of the thorax wall.

Arterial Branches of the Abdominal Aorta

Finally, the aorta passes through the diaphragm into the abdominopelvic cavity, where it becomes the abdominal aorta.

  • Celiac trunk. The celiac trunk is the first branch of the abdominal aorta and has three branches: the left gastric artery supplies the stomach ; the splenic artery supplies the spleen , and the common hepatic artery supplies the liver.
  • Superior mesenteric artery. The unpaired superior mesenteric artery supplies most of the small intestine and the first half of the large intestine or colon .
  • Renal arteries. The renal arteries serve the kidneys.
  • Gonadal arteries. The gonadal arteries supply the gonads, and they are called ovarian arteries in females while in males they are testicular arteries .
  • Lumbar arteries. The lumbar arteries are several pairs of arteries serving the heavy muscles of the abdomen and trunk walls.
  • Inferior mesenteric artery. The inferior mesenteric artery is a small, unpaired artery supplying the second half of the large intestine.
  • Common iliac arteries. The common iliac arteries are the final branches of the abdominal aorta.

Major veins converge on the venae cavae, which enter the right atrium of the heart.

presentation cardiovascular system

Veins Draining into the Superior Vena Cava

Veins draining into the superior vena cava are named in a distal-to-proximal direction; that is, in the same direction the blood flows into the superior vena cava.

  • Radial and ulnar veins . The radial and ulnar veins are deep veins draining the forearm; they unite to form the deep brachial vein , which drains the arm and empties into the axillary vein in the axillary region.
  • Cephalic vein. The cephalic vein provides for the superficial drainage of the lateral aspect of the arm and empties into the axillary vein.
  • Basilic vein. The basilic vein is a superficial vein that drains the medial aspect of the arm and empties into the brachial vein proximally.
  • Median cubital vein. The basilic and cephalic veins are joined at the anterior aspect of the elbow by the median cubital vein, often chosen as the site for blood removal for the purpose of blood testing.
  • Subclavian vein. The subclavian vein receives venous blood from the arm through the axillary vein and from the skin and muscles of the head through the external jugular vein .
  • Vertebral vein. The vertebral vein drains the posterior part of the head.
  • Internal jugular vein. The internal jugular vein drains the dural sinuses of the brain.
  • Brachiocephalic veins. The right and left brachiocephalic veins are large veins that receive venous drainage from the subclavian, vertebral, and internal jugular veins on their respective sides.
  • Azygos vein. The azygos vein is a single vein that drains the thorax and enters the superior vena cava just before it joins the heart.

Veins Draining into the Inferior Vena Cava

The inferior vena cava, which is much longer than the superior vena cava, returns blood to the heart from all body regions below the diaphragm.

  • Tibial veins. The anterior and posterior tibial veins and the fibular vein drain the leg; the posterior tibial veins become the popliteal vein at the knee and then the femoral vein in the thigh; the femoral vein becomes the external iliac vein as it enters the pelvis.
  • Great saphenous veins. The great saphenous veins are the longest veins in the body; they begin at the dorsal venous arch in the foot and travel up the medial aspect of the leg to empty into the femoral vein in the thigh.
  • Common iliac vein. Each common iliac vein is formed by the union of the external iliac vein and the internal iliac vein which drains the pelvis.
  • Gonadal vein. The right gonadal vein drains the right ovary in females and the right testicles in males; the left gonadal vein empties into the left renal veins superiorly.
  • Renal veins. The right and left renal veins drain the kidneys.
  • Hepatic portal vein. The hepatic portal vein is a single vein that drains the digestive tract organs and carries this blood through the liver before it enters the systemic circulation.
  • Hepatic veins. The hepatic veins drain the liver.

Physiology of the Heart

As the heart beats or contracts, the blood makes continuous round trips- into and out of the heart, through the rest of the body, and then back to the heart- only to be sent out again.

The spontaneous contractions of the cardiac muscle cells occurs in a regular and continuous way, giving rhythm to the heart.

Conduction System of the Heart Anatomy and Physiology

  • Cardiac muscle cells. Cardiac muscle cells can and do contract spontaneously and independently, even if all nervous connections are severed.
  • Rhythms. Although cardiac muscles can beat independently, the muscle cells in the different areas of the heart have different rhythms.
  • Intrinsic conduction system. The intrinsic conduction system, or the nodal system , that is built into the heart tissue sets the basic rhythm.
  • Composition. The intrinsic conduction system is composed of a special tissue found nowhere else in the body; it is much like a cross between a muscle and nervous tissue.
  • Function. This system causes heart muscle depolarization in only one direction- from the atria to the ventricles; it enforces a contraction rate of approximately 75 beats per minute on the heart, thus the heart beats as a coordinated unit.
  • Sinoatrial (SA) node. The SA node has the highest rate of depolarization in the whole system, so it can start the beat and set the pace for the whole heart; thus the term “ pacemaker “.
  • Atrial contraction. From the SA node, the impulse spread through the atria to the AV node, and then the atria contract.
  •   Ventricular contraction. It then passes through the AV bundle, the bundle branches, and the Purkinje fibers, resulting in a “wringing” contraction of the ventricles that begins at the heart apex and moves toward the atria.
  • Ejection. This contraction effectively ejects blood superiorly into the large arteries leaving the heart.

The conduction system occurs systematically through:

  • SA node. The depolarization wave is initiated by the sinoatrial node.
  • Atrial myocardium. The wave then successively passes through the atrial myocardium.
  • Atrioventricular node. The depolarization wave then spreads to the AV node, and then the atria contract.
  • AV bundle. It then passes rapidly through the AV bundle.
  • Bundle branches and Purkinje fibers. The wave then continues on through the right and left bundle branches, and then to the Purkinje fibers in the ventricular walls, resulting in a contraction that ejects blood, leaving the heart.

In a healthy heart, the atria contract simultaneously, then, as they start to relax, contraction of the ventricles begins.

  • Systole. Systole means heart contraction .
  • Diastole. Diastole means heart relaxation .
  • Cardiac cycle. The term cardiac cycle refers to the events of one complete heartbeat, during which both atria and ventricles contract and then relax.
  • Length. The average heart beats approximately 75 times per minute, so the length of the cardiac cycle is normally about 0.8 seconds .
  • Mid-to-late diastole. The cycle starts with the heart in complete relaxation ; the pressure in the heart is low, and blood is flowing passively into and through the atria into the ventricles from the pulmonary and systemic circulations; the semilunar valves are closed, and the AV valves are open; then the atria contract and force the blood remaining in their chambers into the ventricles.
  • Ventricular systole. Shortly after, the ventricular contraction begins, and the pressure within the ventricles increases rapidly, closing the AV valves; when the intraventricular pressure is higher than the pressure in the large arteries leaving the heart, the semilunar valves are forced open, and blood rushes through them out of the ventricles; the atria are relaxed, and their chambers are again filling with blood.
  • Early diastole. At the end of systole, the ventricles relax, the semilunar valves snap shut, and for a moment the ventricles are completely closed chambers; the intraventricular pressure drops and the AV valves are forced open; the ventricles again begin refilling rapidly with blood, completing the cycle.
  • First heart sound. The first heart sound, “lub” , is caused by the closing of the AV valves.
  •  Second heart sound. The second heart sound, “dub” , occurs when the semilunar valves close at the end of systole.

Cardiac output is the amount of blood pumped out by each side of the heart in one minute. It is the product of the heart rate and the stroke volume .

  • Stroke volume. Stroke volume is the volume of blood pumped out by a ventricle with each heartbeat.
  • Regulation of stroke volume . According to Starling’s law of the heart , the critical factor controlling stroke volume is how much the cardiac muscle cells are stretched just before they contract; the more they are stretched , the stronger the contraction will be; and anything that increases the volume or speed of venous return also increases stroke volume and force of contraction.
  • Factors modifying basic heart rate. The most important external influence on heart rate is the activity of the autonomic nervous system , as well as physical factors (age, gender, exercise, and body temperature).

A fairly good indication of the efficiency of a person’s circulatory system can be obtained by taking arterial blood and blood pressure measurements.

Arterial pulse pressure and blood pressure measurements, along with those of respiratory rate and body temperature, are referred to collectively as vital signs in clinical settings.

  • Arterial pulse. The alternating expansion and recoil of an artery that occurs with each beat of the left ventricle create a pressure wave-a pulse- that travels through the entire arterial system.
  • Normal pulse rate. Normally, the pulse rate (pressure surges per minute) equals the heart rate, so the pulse averages 70 to 76 beats per minute in a normal resting person.
  • Pressure points. There are several clinically important arterial pulse points, and these are the same points that are compressed to stop blood flow into distal tissues during hemorrhage , referred to as pressure points.
  • Blood pressure. Blood pressure is the pressure the blood exerts against the inner walls of the blood vessels, and it is the force that keeps blood circulating continuously even between heartbeats.
  • Blood pressure gradient. The pressure is highest in the large arteries and continues to drop throughout the systemic and pulmonary pathways, reaching either zero or negative pressure at the venae cavae.
  • Measuring blood pressure. Because the heart alternately contracts and relaxes, the off-and-on flow of the blood into the arteries causes the blood pressure to rise and fall during each beat, thus, two arterial blood pressure measurements are usually made: systolic pressure (the pressure in the arteries at the peak of ventricular contraction) and diastolic pressure (the pressure when the ventricles are relaxing).
  • Peripheral resistance. Peripheral resistance is the amount of friction the blood encounters as it flows through the blood vessels.
  • Neural factors. The parasympathetic division of the autonomic nervous system has little or no effect on blood pressure, but the sympathetic division has the major action of causing vasoconstriction or narrowing of the blood vessels, which increases blood pressure.
  • Renal factors. The kidneys play a major role in regulating arterial blood pressure by altering blood volume, so when blood pressure increases beyond normal, the kidneys allow more water to leave the body in the urine , then blood volume decreases which in turn decreases blood pressure.
  • Temperature. In general, cold has a vasoconstricting effect, while heat has a vasodilating effect.
  • Chemicals. Epinephrine increases both heart rate and blood pressure; nicotine increases blood pressure by causing vasoconstriction; alcohol and histamine cause vasodilation and decreased blood pressure.
  • Diet. Although medical opinions tend to change and are at odds from time to time, it is generally believed that a diet low in salt , saturated fats , and cholesterol help to prevent hypertension , or high blood pressure.

The right and left sides of the heart work together in achieving a smooth-flowing blood circulation .

presentation cardiovascular system

  • Entrance to the heart. Blood enters the heart through two large veins, the inferior and superior vena cava, emptying oxygen-poor blood from the body into the right atrium of the heart.
  • Atrial contraction. As the atrium contracts, blood flows from the right atrium to the right ventricle through the open tricuspid valve.
  • Closure of the tricuspid valve. When the ventricle is full, the tricuspid valve shuts to prevent blood from flowing backward into the atria while the ventricle contracts.
  • Ventricle contraction. As the ventricle contracts, blood leaves the heart through the pulmonic valve, into the pulmonary artery, and to the lungs where it is oxygenated.
  • Oxygen-rich blood circulates. The pulmonary vein empties oxygen-rich blood from the lungs into the left atrium of the heart.
  • Opening of the mitral valve. As the atrium contracts, blood flows from your left atrium into your left ventricle through the open mitral valve.
  • Prevention of backflow. When the ventricle is full, the mitral valve shuts. This prevents blood from flowing backward into the atrium while the ventricle contracts.
  • Blood flow to the systemic circulation. As the ventricle contracts, blood leaves the heart through the aortic valve, into the aorta, and to the body.

Substances tend to move to and from the body cells according to their concentration gradients.

  • Capillary network. Capillaries form an intricate network among the body’s cells such that no substance has to diffuse very far to enter or leave a cell.
  • Routes. Basically, substances leaving or entering the blood may take one of four routes across the plasma membranes of the single layer of endothelial cells forming the capillary wall.
  • Lipid-soluble substances. As with all cells, substances can diffuse directly through their plasma membranes if the substances are lipid-soluble.
  • Lipid-insoluble substances. Certain lipid-insoluble substances may enter or leave the blood and/or pass through the plasma membranes within vesicles, that is, by endocytosis or exocytosis .
  • Intercellular clefts. Limited passage of fluid and small solutes is allowed by intercellular clefts (gaps or areas of plasma membrane not joined by tight junctions), so most of our capillaries have intercellular clefts.
  • Fenestrated capillaries. Very free passage of small solutes and fluid is allowed by fenestrated capillaries, and these unique capillaries are found where absorption is a priority or where filtration occurs.

The capacity of the heart for work decreases with age. Older peoples’ rate is slower to respond to stress and slower to return to normal after periods of physical activity . Changes in arteries occur frequently which can negatively affect blood supply.

Health promotion teaching can include risk detection and reduction for cardiovascular diseases, blood pressure and cholesterol level monitoring, ideal weight maintenance, and a low- sodium diet.

Craving more insights? Dive into these related materials to enhance your study journey!

  • Anatomy and Physiology Nursing Test Banks . This nursing test bank includes questions about Anatomy and Physiology and its related concepts such as: structure and functions of the human body, nursing care management of patients with conditions related to the different body systems.

7 thoughts on “Cardiovascular System Anatomy and Physiology”

very informative!

So great work that could help alot of nurses all over the world, I appreciate it so much.

Nurseslabs have done a very nice work. I wish them good health and strength to continue with the good work.

This excerpt was a magnificent essay of the “Heart Human”.My daughter Arlene Rivera is also an RN and this you wrote about all the heart makes me feel better to know about the knowledge you people possess.Thanks.

In the pathway above, the right subclavian vein is incorrectly labeled as the right pulmonary artery.

For the first time since i leave Nursing school I have now fully understood the cardiovascular system. Keep the good work Matt Vera, you are the best.

Hey Alex, Thank you so much for your kind words! I’m thrilled to hear that our explanations have helped you gain a better understanding of the cardiovascular system. It’s always wonderful to see the impact of educational resources on students and professionals alike.

If there are any more topics or concepts within nursing or healthcare that you’d like to explore or if you have any questions, please don’t hesitate to reach out. Your curiosity and dedication to learning are truly commendable! 🩺🫁📚✨

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NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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StatPearls [Internet].

Cardiovascular disease.

Edgardo Olvera Lopez ; Brian D. Ballard ; Arif Jan .

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Last Update: August 22, 2023 .

  • Continuing Education Activity

The cardiovascular system consists of the heart and its blood vessels. A wide array of problems can arise within the cardiovascular system, a few of which include endocarditis, rheumatic heart disease, and conduction system abnormalities. Cardiovascular disease, also known as heart disease, refers to the following 4 entities: coronary artery disease (CAD) which is also referred to as coronary heart disease (CHD), cerebrovascular disease, peripheral artery disease (PAD), and aortic atherosclerosis. CAD results from decreased myocardial perfusion that causes angina due to ischemia and can result in myocardial infarction (MI), and/or heart failure. It accounts for one-third to one-half of all cases of cardiovascular disease. Cerebrovascular disease is the entity associated with strokes, also termed cerebrovascular accidents, and transient ischemic attacks (TIAs). Peripheral arterial disease (PAD) is arterial disease predominantly involving the limbs that may result in claudication. Aortic atherosclerosis is the entity associated with thoracic and abdominal aneurysms. This activity reviews the evaluation and treatment of cardiovascular disease and the role of the medical team in evaluating and treating these conditions.

  • Review the cause of coronary artery disease.
  • Describe the pathophysiology of atherosclerosis.
  • Summarize the treatment options for heart disease.
  • Outline the evaluation and treatment of cardiovascular disease and the role of the medical team in evaluating and treating this condition.
  • Introduction

The cardiovascular system consists of the heart and blood vessels. [1]  There is a wide array of problems that may arise within the cardiovascular system, for example, endocarditis, rheumatic heart disease, abnormalities in the conduction system, among others, cardiovascular disease (CVD) or heart disease refer to the following 4 entities that are the focus of this article [2] :

  • Coronary artery disease (CAD): Sometimes referred to as Coronary Heart Disease (CHD), results from decreased myocardial perfusion that causes angina, myocardial infarction (MI), and/or heart failure. It accounts for one-third to one-half of the cases of CVD.
  • Cerebrovascular disease (CVD): Including stroke and transient ischemic attack (TIA)
  • Peripheral artery disease (PAD): Particularly arterial disease involving the limbs that may result in claudication
  • Aortic atherosclerosis:  Including thoracic and abdominal aneurysms

Although CVD may directly arise from different etiologies such as emboli in a patient with atrial fibrillation resulting in ischemic stroke, rheumatic fever causing valvular heart disease, among others, addressing risks factors associated to the development of atherosclerosis is most important because it is a common denominator in the pathophysiology of CVD.

The industrialization of the economy with a resultant shift from physically demanding to sedentary jobs, along with the current consumerism and technology-driven culture that is related to longer work hours, longer commutes, and less leisure time for recreational activities, may explain the significant and steady increase in the rates of CVD during the last few decades. Specifically, physical inactivity, intake of a high-calorie diet, saturated fats, and sugars are associated with the development of atherosclerosis and other metabolic disturbances like metabolic syndrome, diabetes mellitus, and hypertension that are highly prevalent in people with CVD. [3] [2] [4] [5]

According to the INTERHEART study that included subjects from 52 countries, including high, middle, and low-income countries, 9 modifiable risks factors accounted for 90% of the risk of having a first MI: smoking, dyslipidemia, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits and vegetables, regular alcohol consumption, and physical inactivity. It is important to mention that in this study 36% of the population-attributable risk of MI was accounted to smoking. [6]

Other large cohort studies like the Framingham Heart Study [7] and the Third National Health and Nutrition Examination Survey (NHANES III) [5] have also found a strong association and predictive value of dyslipidemia, high blood pressure, smoking, and glucose intolerance. Sixty percent to 90% of CHD events occurred in subjects with at least one risk factor.

These findings have been translated into health promotion programs by the American Heart Association with emphasis on seven recommendations to decrease the risk of CVD: avoiding smoking, being physically active, eating healthy, and keeping normal blood pressure, body weight, glucose, and cholesterol levels. [8] [9]

On the other hand, non-modifiable factors as family history, age, and gender have different implications. [4] [7] Family history, particularly premature atherosclerotic disease defined as CVD or death from CVD in a first-degree relative before 55 years (in males) or 65 years (in females) is considered an independent risk factor. [10] There is also suggestive evidence that the presence of CVD risk factors may differently influence gender. [4] [7]  For instance, diabetes and smoking more than 20 cigarettes per day had increased CVD risk in women compared to men. [11] Prevalence of CVD increases significantly with each decade of life. [12]  

The presence of HIV (human immunodeficiency virus), [13]  history of mediastinal or chest wall radiation, [14]  microalbuminuria, [15] , increased inflammatory markers [16] [17]  have also been associated with an increased rate and incidence of CVD. 

Pointing out specific diet factors like meat consumption, fiber, and coffee and their relation to CVD remains controversial due to significant bias and residual confounding encountered in epidemiological studies. [18] [19]

  • Epidemiology

Cardiovascular diseases (CVD) remain among the 2 leading causes of death in the United States since 1975 with 633,842 deaths or 1 in every 4 deaths, heart disease occupied the leading cause of death in 2015 followed by 595,930 deaths related to cancer. [2]  CVD is also the number 1 cause of death globally with an estimated 17.7 million deaths in 2015, according to the World Health Organization (WHO). The burden of CVD further extends as it is considered the most costly disease even ahead of Alzheimer disease and diabetes with calculated indirect costs of $237 billion dollars per year and a projected increased to $368 billion by 2035. [20]

Although the age-adjusted rate and acute mortality from MI have been declining over time, reflecting the progress in diagnosis and treatment during the last couple of decades, the risk of heart disease remains high with a calculated 50% risk by age 45 in the general population. [7] [21]  The incidence significantly increases with age with some variations between genders as the incidence is higher in men at younger ages. [2]  The difference in incidence narrows progressively in the post-menopausal state. [2]

  • Pathophysiology

Atherosclerosis is the pathogenic process in the arteries and the aorta that can potentially cause disease as a consequence of decreased or absent blood flow from stenosis of the blood vessels. [22]

It involves multiple factors dyslipidemia, immunologic phenomena, inflammation, and endothelial dysfunction. These factors are believed to trigger the formation of fatty streak, which is the hallmark in the development of the atherosclerotic plaque [23] ; a progressive process that may occur as early as in the childhood. [24]  This process comprises intimal thickening with subsequent accumulation of lipid-laden macrophages (foam cells) and extracellular matrix, followed by aggregation and proliferation of smooth muscle cells constituting the formation of the atheroma plaque. [25]  As this lesions continue to expand, apoptosis of the deep layers can occur, precipitating further macrophage recruitment that can become calcified and transition to atherosclerotic plaques. [26]

Other mechanisms like arterial remodeling and intra-plaque hemorrhage play an important role in the delay and accelerated the progression of atherosclerotic CVD but are beyond the purpose of this article. [27]

  • History and Physical

The clinical presentation of cardiovascular diseases can range from asymptomatic (e.g., silent ischemia, angiographic evidence of coronary artery disease without symptoms, among others) to classic presentations as when patients present with typical anginal chest pain consistent of myocardial infarction and/or those suffering from acute CVA presenting with focal neurological deficits of sudden onset. [28] [29] [28]

Historically, coronary artery disease typically presents with angina that is a pain of substernal location, described as a crushing or pressure in nature, that may radiate to the medial aspect of the left upper extremity, to the neck or the jaw and that can be associated with nausea, vomiting, palpitations, diaphoresis, syncope or even sudden death. [30]  Physicians and other health care providers should be aware of possible variations in symptom presentation for these patients and maintain a high index of suspicion despite an atypical presentation, for example, dizziness and nausea as the only presenting symptoms in patients having an acute MI [31] ), particularly in people with a known history of CAD/MI and for those with the presence of CVD risk factors. [32] [33] [34] [33] [32]  Additional chest pain features suggestive of ischemic etiology are the exacerbation with exercise and or activity and resolution with rest or nitroglycerin. [35]

Neurologic deficits are the hallmark of cerebrovascular disease including TIA and stroke where the key differentiating factor is the resolution of symptoms within 24 hours for patients with TIA. [36]  Although the specific symptoms depend on the affected area of the brain, the sudden onset of extremity weakness, dysarthria, and facial droop are among the most commonly reported symptoms that raise concern for a diagnosis of a stroke. [37] [38]  Ataxia, nystagmus and other subtle symptoms as dizziness, headache, syncope, nausea or vomiting are among the most reported symptoms with people with posterior circulation strokes challenging to correlate and that require highly suspicion in patients with risks factors. [39]

Patients with PAD may present with claudication of the limbs, described as a cramp-like muscle pain precipitated by increased blood flow demand during exercise that typically subsides with rest. [40] Severe PAD might present with color changes of the skin and changes in temperature. [41]  

Most patients with thoracic aortic aneurysm will be asymptomatic, but symptoms can develop as it progresses from subtle symptoms from compression to surrounding tissues causing cough, shortness of breath or dysphonia, to the acute presentation of sudden crushing chest or back pain due to acute rupture. [42]  The same is true for abdominal aortic aneurysms (AAA) that cause no symptoms in early stages to the acute presentation of sudden onset of abdominal pain or syncope from acute rupture. [43]

A thorough physical examination is paramount for the diagnosis of CVD. Starting with a general inspection to look for signs of distress as in patients with angina or with decompensated heart failure, or chronic skin changes from PAD. Carotid examination with the patient on supine position and the back at 30 degrees for the palpation and auscultation of carotid pulses, bruits and to evaluate for jugular venous pulsations on the neck is essential. Precordial examination starting with inspection, followed by palpation looking for chest wall tenderness, thrills, and identification of the point of maximal impulse should then be performed before auscultating the precordium. Heart sounds auscultation starts in the aortic area with the identification of the S1 and S2 sounds followed by characterization of murmurs if present. Paying attention to changes with inspirations and maneuvers to correctly characterize heart murmurs is encouraged. Palpating peripheral pulses with bilateral examination and comparison when applicable is an integral part of the CVD examination. [44]

Thorough clinical history and physical exam directed but not limited to the cardiovascular system are the hallmarks for the diagnosis of CVD. Specifically, a history compatible with obesity, angina, decreased exercise tolerance, orthopnea, paroxysmal nocturnal dyspnea, syncope or presyncope, and claudication should prompt the clinician to obtain a more detailed history and physical exam and, if pertinent, obtain ancillary diagnostic test according to the clinical scenario (e.g., electrocardiogram and cardiac enzymes for patients presenting with chest pain). 

Besides a diagnosis prompted by clinical suspicion, most of the efforts should be oriented for primary prevention by targeting people with the presence of risk factors and treat modifiable risk factors by all available means. All patient starting at age 20 should be engaged in the discussion of CVD risk factors and lipid measurement. [9]  Several calculators that use LDL-cholesterol and HDL-cholesterol levels and the presence of other risk factors calculate a 10-year or 30-year CVD score to determine if additional therapies like the use of statins and aspirin are indicated for primary prevention, generally indicated if such risk is more than ten percent. [10]  Like other risk assessment tools, the use of this calculators have some limitations, and it is recommended to exert precaution when assessing patients with diabetes and familial hypercholesterolemia as their risk can be underestimated. Another limitation to their use is that people older than 79 were usually excluded from the cohorts where these calculators were formulated, and individualized approach for these populations is recommended by discussing risk and benefits of adjunctive therapies and particular consideration of life expectancy. Some experts recommend a reassessment of CVD risk every 4 to 6 years. [9]

Preventative measures like following healthy food habits, avoiding overweight and following an active lifestyle are pertinent in all patients, particularly for people with non-modifiable risk factors such as family history of premature CHD or post-menopause. [9] [8]

The use of inflammatory markers and other risk assessment methods as coronary artery calcification score (CAC) are under research and have limited applications that their use should not replace the identification of people with known risk factors, nonetheless these resources remain as promising tools in the future of primary prevention by detecting people with subclinical atherosclerosis at risk for CVD. [45]

  • Treatment / Management

Management of CVD is very extensive depending on the clinical situation (catheter-directed thrombolysis for acute ischemic stroke, angioplasty for peripheral vascular disease, coronary stenting for CHD); however, patients with known CVD should be strongly educated on the need for secondary prevention by risk factor and lifestyle modification. [9] [46]

  • Differential Diagnosis
  • Acute pericarditis
  • Angina pectoris
  • Artherosclerosis
  • Coronary artery vasospasm
  • Dilated cardiomyopathy
  • Giant cell arteritis
  • Hypertension
  • Hypertensive heart disease
  • Kawasaki disease
  • Myocarditis

The prognosis and burden of CVD have been discussed in other sections.

  • Complications

The most feared complication from CVD is death and, as explained above, despite multiple discoveries in the last decades CVD remains in the top leading causes of death all over the world owing to the alarming prevalence of CVD in the population. [2]  Other complications as the need for longer hospitalizations, physical disability and increased costs of care are significant and are the focus for health-care policymakers as it is believed they will continue to increase in the coming decades. [20]

For people with heart failure with reduced ejection fraction (HFreEF) of less than 35%, as the risk of life-threatening arrhythmias is exceedingly high in these patients, current guidelines recommend the implantation of an implantable-cardioverter defibrillator (ICD) for those with symptoms equivalent to a New York Heart Association (NYHA) Class II-IV despite maximal tolerated medical therapy. [47]

Strokes can leave people with severe disabling sequelae like dysarthria or aphasia, dysphagia, focal or generalized muscle weakness or paresis that can be temporal or cause permanent physical disability that may lead to a complete bedbound state due to hemiplegia with added complications secondary to immobility as is the higher risk of developing urinary tract infections and/or risk for thromboembolic events. [48] [49]

There is an increased risk of all-cause death for people with PAD compared to those without evidence of peripheral disease. [50]  Chronic wounds, physical limitation, and limb ischemia are among other complications from PAD. [51]

  • Consultations

An interprofessional approach that involves primary care doctors, nurses, dietitians, cardiologists, neurologists, and other specialists is likely to improve outcomes. This has been shown to be beneficial in patients with heart failure, [52]  coronary disease, [53]  and current investigations to assess the impact on other forms of CVD are under planning and promise encouraging results.

  • Deterrence and Patient Education

Efforts should be directed toward primary prevention by leading a healthy lifestyle, and an appropriate diet starting as early as possible with the goal of delay or avoid the initiation of atherosclerosis as it relates to the future risk of CVD. The AHA developed the concept of "ideal cardiovascular health" defined by the presence of [8] :

  • Ideal health behaviors: Nonsmoking, body mass index less than 25 kg/m2, physical activity at goal levels, and the pursuit of a diet consistent with current guideline recommendations
  • Ideal health factors: Untreated total cholesterol less than 200 mg/dL, untreated blood pressure less than 120/80 mm Hg, and fasting blood glucose less than 100 mg/dL) with the goal to improve the health of all Americans with an expected decrease in deaths from CVD by 20%

Specific attention should be made to people at higher risk for CVD as are people with diabetes, hypertension, hyperlipidemia, smokers, and obese patients. Risk factors modification by controlling their medical conditions, avoiding smoking, taking appropriate measures to lose weight and maintaining an active lifestyle is of extreme importance. [8] [9] [10] The recommendations on the use of statins and low-dose aspirin for primary and secondary prevention has been discussed in other sections.

  • Pearls and Other Issues

Cardiovascular disease generally refers to 4 general entities: CAD, CVD, PVD, and aortic atherosclerosis. 

CVD is the main cause of death globally.

Measures aimed to prevent the progression of atherosclerosis are the hallmark for primary prevention of CVD.

Risk factor and lifestyle modification are paramount in the prevention of CVD.

  • Enhancing Healthcare Team Outcomes

An interprofessional and patient-oriented approach can help to improve outcomes for people with cardiovascular disease as shown in patients with heart failure (HF) who had better outcomes when the interprofessional involvement of nurses, dietitians, pharmacists, and other health professionals was used (Class 1A). [52]

Similarly, positive results were obtained in people in an intervention group who were followed by an interprofessional team comprised of pharmacists, nurses and a team of different physicians. This group had a reduction in all-cause mortality associated with CAD by 76% compared to the control group. [53]  Healthcare workers should educate the public on lifestyle changes and reduce the modifiable risk factors for heart disease to a minimum.

  • Review Questions
  • Access free multiple choice questions on this topic.
  • Comment on this article.

Atherosclerosis as a result of coronary heart disease. Contributed by National Heart, Lung and Blood Institute (NIH)

Coronary artery disease Image courtesy S Bhimji MD

Disclosure: Edgardo Olvera Lopez declares no relevant financial relationships with ineligible companies.

Disclosure: Brian Ballard declares no relevant financial relationships with ineligible companies.

Disclosure: Arif Jan declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

  • Cite this Page Olvera Lopez E, Ballard BD, Jan A. Cardiovascular Disease. [Updated 2023 Aug 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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the cardiovascular system

The Cardiovascular System

Apr 07, 2019

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The Cardiovascular System. Functions of Cardiovascular System. Pump blood through the body Brings oxygen and nutrients to all body cells Removes waste. Hollow cone-shaped muscular pump Located in the thoracic cavity, just above the diaphragm The pericardium encloses the heart

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  • parasympathetic fibers
  • pulmonary arteries
  • own blood supply
  • oxygenated blood returns
  • smallest diameter blood vessels

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Functions of Cardiovascular System • Pump blood through the body • Brings oxygen and nutrients to all body cells • Removes waste

Hollow cone-shaped muscular pump Located in the thoracic cavity, just above the diaphragm The pericardium encloses the heart Pericardial cavity – space between the parietal and visceral layers of the pericardium Structure of the Heart

3 layers Epicardium – outer layer, protects the heart by reducing friction (serous membranes) Myocardium – thick middle layer mostly composed of muscle Endocardium – inner layer consists of connective tissue and epithelium Wall of the heart

4 hollow chambers 2 atria (left and right) 2 ventricles (left and right) Septum separates the atrium and ventricles on the right and left sides Keeps blood from right side of heart from mixing with blood from the left side of the heart Valves Atrioventricular valve (AV Valve) – ensures one way flow of blood between the atria and ventricles Tricuspid valve Bicuspid valve (mitral valve) Pulmonary valve Aortic valve Heart Chambers and valves

Path of Blood Through the Heart • Low Oxygen/High Carbon Dioxide • Enters right atrium through vena cavae • Contraction of atrium • Tricuspid valve • Right ventricle • Contraction of Ventricle (tricuspid valve closes) • Pulmonary valve to pulmonary arteries to capillaries in lungs (alveoli) • High Oxygen/Low Carbon Dioxide • Oxygenated blood returns to heart through the pulmonary veins • Enters left atrium • Contraction of atrium • Bicuspid valve • Left ventricle • Contraction of Ventricle (bicuspid valve closes) • Aortic valve to aorta and its branches

The heart must have its own blood supply in order for it to function (myocardium must have oxygen for muscles to contract) Coronary arteries (brings blood to heart tissue) Cardiac veins (carries blood away from heart tissue) Blood Supply to the Heart

The heart chambers function in a coordinated fashion Systole – contraction Diastole – relaxation When the atria contract, the ventricles relax. When the ventricles contract, the atria relax Cardiac Cycle – series of events constitutes a complete heartbeat Heart Actions

Cardiac Cycle

Cardiac Cycle • During the cardiac cycle, pressure within the heart chambers rises and falls.

Heart Sounds • The heart beat through a stethoscope sounds like lubb –dupp • Sounds are due to vibrations in the heart tissues associated with closing of the valves • Lubb – ventricular contraction when the A-V valves are closing • Dupp – ventricular relaxation when the pulmonary and aortic valves are closing

Clumps of specialized cardiac muscle tissue distribute impulses throughout the myocardium instead of contracting Sinoatrial node (SA node) – can initiate impulses without stimulation from nerve fibers Pacemaker of the heart Atrioventricular node (AV node) Cardiac Conduction System

Regulation of Cardiac Cycle • The volume of blood pumped changes to accommodate cellular requirements. (ie. strenuous exercise) • Since the S-A node normally controls heart rate, changes in this rate are often a response to motor impulses carried by the parasympathetic and sympathetic nerve fibers • The cardiac control center of the medulla oblongata maintains balance between the inhibitory effects of parasympathetic fibers and the excitatory effects of sympathetic fibers • Impulses from the cerebrum and hypothalamus also influence the cardiac control center

Blood Vessels • Blood Vessels form a closed circuit of tubes that carries blood from the heart to cells and back again • Arteries – strong, carry blood away from the heart under high pressure • Arterioles – thinner, finer branches • Capillaries – smallest diameter blood vessels, connect smallest arterioles and smallest venules. • Venules – microscopic vessels that continue from the capillaries • Veins – carry blood back to the atria

Blood Vessels • Remember, the walls of arteries and veins contain smooth muscle that can contract, reducing the diameter of the vessel (vasoconstriction) • Vasodilation – relaxation of the muscle fibers, causing the diameter of the vessel to increase

Exchanges in Capillaries • Gases, nutrients, and metabolic by-products are exchanged between the blood in capillaries an the tissue fluid surrounding body cells. • The substances exchanged move through capillary walls by diffusion and osmosis (based on difference in concentration gradients) and filtration (force molecules through a membrane with hydrostatic pressure)

Veins • Return blood to the heart • Many veins, particularly those in the upper and lower limbs, contain flap-like valves which close if blood begins to back up into a vein. • They aid in returning blood to the heart by preventing blood from flowing in the opposite direction

Blood Pressure • Most commonly refers to pressure in arteries supplied by branches of the aorta. • Systolic pressure – the maximum pressure during ventricular contraction • Diastolic pressure – the lowest pressure that remains in the arteries during ventricular relaxation

Factors Influencing Arterial Blood Pressure • Heart action • Stroke volume – the volume of blood discharged from the left ventricle with each contraction • Cardiac output – the volume of blood discharged from the left ventricle per minute • Blood Volume – the sum of all the formed elements and plasma in the vascular system • Peripheral Resistance – friction between the blood and the walls of the blood vessels (contraction and dilation of vessels) • Blood Viscosity – the ease with which a fluid’s molecules flow past one another • “blood is thicker than water

Control of Blood Pressure • Read: Control of Blood Pressure (pg 348-350) and summarize in your notes • Complete CYR questions on pg 350

ORQ • Cigarette smoke contains thousands of chemicals, including nicotine and carbon monoxide. Nicotine constricts blood vessels. Carbon monoxide prevents oxygen from binding to hemoglobin. How do these two components of smoke affect the cardiovasuclar system?

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The Circulatory System PowerPoint

The Circulatory System PowerPoint

Subject: Biology

Age range: 14-16

Resource type: Lesson (complete)

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Last updated

18 February 2024

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presentation cardiovascular system

This interactive PowerPoint covers the function of the circulatory system, advantages of double circulation, the structures of the heart and the structure and function of blood vessels.

Activities and practice questions are included within the PowerPoint along with model answers.

Recommended time: 2-4 lessons.

Useful for teaching: body systems, the circulatory system, animal transport and human physiology. Suitable for IB, A Level, VCE, GCSE and IGCSE Biology.

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The Circulatory System PowerPoint and Worksheets

Interactive PowerPoint covers the function of the circulatory system, advantages of double circulation, the structures of the heart and the structure and function of blood vessels. Activities and practice questions are included within the PowerPoint along with model answers. Worksheets require students to label the structures of the heart, compare the structure and function of blood vessels (arteries, veins and capillaries) and identify and state the functions of the components of blood. Answers are included. Useful for teaching: body systems, the circulatory system, animal transport and human physiology. Suitable for IB, A Level, VCE, GCSE and IGCSE Biology. Recommended time: 3-6 lessons.

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  • Case report
  • Open access
  • Published: 22 February 2024

Pembrolizumab-induced myocarditis with complete atrioventricular block and concomitant myositis in a metastatic bladder cancer patient: a case report and review of the literature

  • R. Saad 1 ,
  • A. Ghaddar 1 &
  • R. M. Zeenny   ORCID: orcid.org/0000-0002-5443-7780 1 , 2  

Journal of Medical Case Reports volume  18 , Article number:  107 ( 2024 ) Cite this article

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The cardiovascular system is among the least systems affected by immune-related adverse events. We report a rare life-threatening case of pembrolizumab-induced myocarditis with complete atrioventricular block and concomitant myositis in a metastatic bladder cancer patient.

Case presentation

An 82-year-old Caucasian female with invasive urothelial carcinoma, started on first-line pembrolizumab, was admitted four days after receiving her second dose for severe asthenia, diffuse muscle aches, neck pain, and lethargy. In the emergency department, she had several episodes of bradycardia reaching 40 beats per minute associated with general discomfort and fatigue. Electrocardiography showed a third-degree atrioventricular heart block, while the patient remained normotensive. Cardiac damage parameters were altered with elevated levels of creatine phosphokinase of 8930 U/L, suggestive of immune checkpoint inhibitor-induced myositis, and troponin T of 1.060 ng/mL. Transthoracic echocardiography showed a preserved ejection fraction. Pembrolizumab-induced myocarditis was suspected. Therefore, treatment was initiated with high-dose glucocorticoids for 5 days, followed by a long oral steroid taper. A pacemaker was also implanted. Treatment resulted in the resolution of heart block and a decrease in creatine phosphokinase to the normal range.

Life-threatening cardiac adverse events in the form of myocarditis may occur with pembrolizumab use, warranting vigilant cardiac monitoring. Troponin monitoring in high-risk patients, along with baseline echocardiography may help identify this complication promptly to prevent life-threatening consequences.

Peer Review reports

In recent years, immune checkpoint inhibitors (ICIs) have transformed the landscape of cancer treatment [ 1 ]. Malignant cells evade the recognition and destruction by the immune system by exploiting immune checkpoint receptors, such as the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1). Immune checkpoint inhibitors are drugs designed to disrupt these interactions, reactivating the immune system, and generating potent and long-lasting antitumor responses [ 2 , 3 ]. Up to now, the US Food and Drug Administration (FDA) has approved several ICIs for cancer treatment, including one CTLA-4 inhibitor (ipilimumab), three PD-1 inhibitors (nivolumab, pembrolizumab, cemiplimab), and three PD-L1 inhibitors (atezolizumab, avelumab, durvalumab) [ 4 ]. Although ICIs are overall well tolerated, several immune-related adverse events (irAEs) have been reported, which are due to the suppression of immune regulation and inflammatory reactions against the normal tissues [ 5 ]. These include hepatitis (< 10%), colitis (1–2%), endocrine disorders (1–6%), and skin lesions (30–40%) [ 5 ]. The cardiovascular system is among the least systems affected by irAEs with pericarditis, myocardial fibrosis, pericardial effusion, and myocarditis being some of the possible side effects [ 6 ]. Although very rare, myocarditis is being increasingly reported with the use of ICIs and has been estimated to occur in 0.06–1% of clinical trial patients receiving immunotherapy [ 6 ]. Although data on the presentation, diagnosis, and outcomes are limited, myocarditis often appears as a fulminant and severe side effect of ICIs [ 7 ]. Hence, a high degree of awareness is essential to detect this rare complication in patients on ICI therapy to initiate appropriate treatment promptly.

Pembrolizumab is uncommonly associated in the literature with immune checkpoint inhibitor-associated myocarditis (ICIM) when compared to other ICIs [ 8 , 9 , 10 ], with a low incidence of the life-threatening nature of this side effect [ 7 , 9 ]. Moreover, ICIM is more described in melanoma and non-small cell lung cancer patients, while urothelial carcinoma is rarely mentioned [ 8 , 9 ]. Only three cases of pembrolizumab-induced myocarditis with complete AV block in bladder cancer patients were identified [ 10 , 11 , 12 ]. We report a rare life-threatening case of pembrolizumab-induced myocarditis with a complete heart block and concomitant myositis in an 82-year-old bladder cancer patient.

An 82-year-old Caucasian female with a history of hypertension on candesartan, diabetes mellitus type 2 poorly controlled on glimepiride, repaglinide, and vildagliptin, dyslipidemia on fenofibrate, and no history of auto-immune disease, was treated with her second dose of the first-line pembrolizumab for invasive poorly differentiated urothelial carcinoma.

The patient was diagnosed with papillary transitional cell carcinoma of the bladder in 2009 for which she underwent a transurethral resection (TURBT). This was followed by another resection in 2013, followed by gemcitabine chemotherapy, then several resections in 2015, followed by chemoradiation with cisplatin and gemcitabine. She underwent resections in 2016 and 2018, followed by intravesical instillation of mitomycin C. She presented in July 2019 for an increased size caruncle which was resected. The tissue was positive for invasive poorly-differentiated urothelial carcinoma, expressing PD-L1 in 50% of the tumor cells. A CT of the abdomen and pelvis showed enlarged bilateral inguinal lymph nodes suggestive of metastatic disease. Subsequently, a lymph node biopsy confirmed the diagnosis of metastatic poorly differentiated urothelial carcinoma stage IV A (AJCC 8th Edition) [ 13 ] for which she was started on first-line immunotherapy with pembrolizumab 200 mg intravenous drip every 3 weeks. She received her first cycle in September 2019 without complications, presented for her second cycle 21 days later with mild fatigue, and received her second dose. Four days later she contacted her oncologist complaining of severe neck pain and was advised to present to the emergency department.

The patient was admitted to the hospital 25 days after the initial dose of pembrolizumab for severe asthenia, diffuse muscle aches, neck pain, and lethargy. She denied chest pain, orthopnea, or paroxysmal nocturnal dyspnea. In the ED, she had several episodes of bradycardia reaching 40–46 beats per minute associated with general discomfort and fatigue. The initial workup revealed a third-degree atrioventricular (AV) heart block in the electrocardiogram (ECG; Fig.  1 ) while the patient was normotensive. Moreover, cardiac damage parameters were altered with elevated levels of creatine phosphokinase kinase (CPK) of 8930 U/L [normal range (NR) 20–165 U/L], suggestive of severe rhabdomyolysis, and troponin T (TnT) of 1.060 ng/mL (NR ≤ 0.030 ng/mL) (Table 1 ). Additionally, her serum potassium was elevated (6.5 mmol/L, [NR 3.5–5.1 mmol/L]). Due to these alterations, a transthoracic echocardiogram (TTE) was performed urgently, showing a preserved left ventricular ejection fraction (LVEF). Urine chemistry showed positive myoglobin. Serum creatinine, as well as liver function tests, were within normal limits. The chest radiograph showed a clear lung field. Acetylcholine receptor binding antibodies’ (AChR-Ab) level was positive borderline at 0.31 nmol/L (NR < 0.25 nmol/L; Borderline 0.25–0.4 nmol/L) and antibodies to muscle-specific tyrosine kinase (MuSK-Ab) were negative.

figure 1

Electrocardiogram (ECG) on the day of admission to the emergency department: ECG showing a complete atrioventricular block with a ventricular escape rhythm

Given the elevation of markers of cardiac injury and ECG changes with the absence of other cardiac syndromes or infectious signs, alongside the history of immunotherapy and concomitant myositis, pembrolizumab-induced myocarditis was suspected. An endomyocardial biopsy could not be performed due to the invasive nature of the procedure and the risk of potential acute and chronic complications. Other etiologies of myocarditis (that is, viral myocarditis, giant cell myocarditis, eosinophile myocarditis, endomyocardial fibrosis, sarcoidosis) were excluded. The elevated CPK was linked to pembrolizumab-induced myositis rather than fibrate-induced rhabdomyolysis, knowing the patient was maintained on fenofibrate for several years. It was however judged preferable to discontinue the medication. The borderline positive AChR-Ab was suggestive of possible myasthenia gravis . The patient was started on a dopamine drip and treatment was initiated with high-dose glucocorticoids (1 mg/kg/day of intravenous methylprednisolone) for 5 days. The patient was then transitioned to oral prednisone followed by a long taper over five weeks. A pacemaker was implanted 3 days later. A follow-up ECG showed complete recovery of sinus rhythm and heart rate.

Pembrolizumab is a PD-1 immune checkpoint inhibitor that has significantly increased overall survival in a broad array of cancer types, including melanoma, non-small cell lung cancer, renal cell carcinoma, and microsatellite instability-high or mismatch repair-deficient cancer [ 14 ]. Although recognized as an uncommon adverse reaction, ICIM may result in poor outcomes [ 15 ]. We report in this article a case of life-threatening myocarditis with a complete AV block occurring in an 82-year-old female four days after receiving her second dose of pembrolizumab for invasive urothelial carcinoma. We reviewed the pertinent literature for pembrolizumab and other ICIs-induced myocarditis.

Incidence of myocarditis and fatality outcomes

Myocarditis associated with ICIs is considered a relatively rare adverse event, with a reported incidence of 0.04–1.14% [ 16 , 17 ] increasing up to 2.4% with combination therapy [ 7 ]. However, it is associated with poorer outcomes when compared to other immune-related adverse events, with higher mortality rates ranging between 25 and 50% [ 7 , 8 , 15 , 18 , 19 ].

Pembrolizumab is associated in the literature with a low incidence of ICIM when compared to other immune-checkpoint inhibitors [ 8 , 9 , 10 ], as well as a low incidence of the life-threatening nature of this side effect [ 7 , 9 ]. In our patient, on Naranjo's causality assessment scale, the adverse event was 6 indicating a “probable” reaction to pembrolizumab (Table  2 ) [ 20 ]. Among the 315 patients with ICIM identified in a post-marketing surveillance study by Fan et al. , nivolumab monotherapy had the highest number of case reports with 125 cases (39.6%), followed by the combination of ipilimumab plus nivolumab with 73 cases (23.1%). As for pembrolizumab monotherapy, there were 69 cases reported (29.90%) [ 9 ]. In a retrospective study of data from eight clinical centers by Mahmood et al. , of 35 patients who had myocarditis, 12 were receiving combinations of anti-CTLA-4 and anti-PD1/PD-L1, 11 were on pembrolizumab monotherapy and 7 on nivolumab monotherapy [ 7 ]. On the other hand, the analysis of the incidence of major cardiac events (MACE) showed that 44% of the cases were related to nivolumab, versus 13% with pembrolizumab. In the pharmacovigilance study conducted by Fan et al. using the Food and Drug Administration’s Adverse Event Reporting System (FAERS), the combination of ipilimumab plus nivolumab was significantly associated with myocarditis fatality (65.75%), while nivolumab was the monotherapy mostly correlated with a risk of myocarditis death (50.4%) [ 9 ].

Our patient was receiving pembrolizumab as a first-line treatment for invasive urothelial carcinoma, which is not commonly associated with ICIM in the literature where melanoma and non-small cell lung cancer appears to be more common [ 8 , 9 ]. Only three cases of pembrolizumab-induced myocarditis with complete AV block in bladder cancer patients were identified [ 10 , 11 , 12 ]. The cases describe a pembrolizumab-induced myasthenia gravis [ 10 ] and myositis [ 11 ] followed a few days later by a complete AV block that resulted in death despite aggressive treatment. Similar to our case, the immune-related adverse event occurred in two elderly patients, early in the treatment course. Cardiac biomarkers were elevated, however, ECG was initially normal in the case described by Takai et al. [ 10 ], while a wide QRS complex was identified in the case described by Matsui et al. [ 11 ] Hellman et al. [ 12 ] reported a case of myocarditis with a second-degree AV block along with myositis in a 42-year old bladder cancer patient treated with the combination of pembrolizumab and epacadostat.

Patients’ characteristics

Myocarditis seems to predominantly occur in elderly patients which aligns with our case, with males however being affected more than female patients [ 7 , 9 , 17 ]. Among the 315 patients with ICIM described by Fan et al. [ 9 ] 51.11% were above 65 years of age and 58.41% were men. Advancing age is an important risk factor for cancer [ 21 ]. It is to note that safety data on the use of ICIs in elderly patients is still limited, due to insufficient enrollment in clinical trials [ 22 ]. Underlying auto-immune disease, pre-existing cardiovascular disease, and diabetes mellitus might be risk factors for ICIM [ 6 ]. According to Mahmood et al. , myocarditis cases had a higher prevalence of diabetes mellitus, sleep apnea, and a higher body mass index [ 7 ]. Our patient had uncontrolled type 2 diabetes.

Clinical presentation

The clinical presentation of ICIM can vary from asymptomatic raises in cardiac biomarkers to life-threatening fulminant decompensation, which is the most commonly reported in the literature [ 6 ]. This report describes an uncommon case of pembrolizumab-induced myocarditis with a complete atrioventricular block with the preservation of LVEF. In comparison to the 8 cases of pembrolizumab-inducted myocarditis presented in the systematic review by Atallah-Yunes et al. , four cases had a complete AV block, one of them only with a preserved LVEF. None of the cases occurred in a bladder cancer patient [ 28 ]. Out of the 35 cases of ICIM presented by Mahmood et al. , only 3 experienced a complete heart block with no specification of the implicated agent. 38% of those who developed MACEs had normal LVEF [ 7 ].

In this case report, myocarditis was also associated with myositis and borderline positive AChR-Abs. According to Palaskas et al. in a review article on ICIM, the presence of other immune-related adverse events increases the possibility of ICIM in patients presenting with cardiac symptoms [ 23 ]. Myositis and myasthenia gravis are commonly associated with ICIM [ 24 ]. The suggested explanation is shared antigens between cardiac muscle and skeletal muscles compared with other tissues [ 23 ]. Among the systematic review of the 43 published cases of ICIM by Atallah-Yunes et al. , 29% of the patients had concomitant myositis [ 28 ].

Another interesting finding is that myocarditis with ICI occurs early in the treatment course with ICIs, which aligns with our case where it developed 25 days after treatment initiation, following the second dose of pembrolizumab. This is consistent with the finding of the FAERS database analysis which describes a median time to onset of myocarditis of 23 days [interquartile range (IQR) 14–55 days] [ 9 ]. In the VigiBase study, 64% of the patients who had information available developed ICIM after the first or second dose of ICI. However, late presentations have also been reported in the literature [ 17 ]. Clinicians should maintain a high level of clinical suspicion of this serious adverse event, notably in elderly patients after the first doses of immunotherapy, although diagnosis should also be considered in patients with a long history of treatment with ICIs.

Diagnostic tests

The two most common laboratory tests that may initially be suggestive of myocarditis are elevated serum troponin and natriuretic peptide levels [ 25 ]. In the cohort study of Mahmood et al. , almost all myocarditis cases had a troponin elevation (94%), the degree of troponin elevation (initial level, peak, and discharge level) being a predictor of adverse events, alongside an abnormal ECG (89%) [ 7 ]. A level of Troponin T ≥ 1.5 ng/mL upon discharge was a poorer prognosis, with a fourfold increased risk of MACE. However, a depressed LVEF was not a precondition for serious adverse cardiovascular events, in comparison to non-immune therapy-related myocarditis [ 7 ]. Our patient had a mildly elevated troponin T and an abnormal ECG, with a preserved LVEF. Serum troponin is an inexpensive test that is commonly available, a rise generally suggesting myocyte death [ 26 ]. Consequently, because the onset of myocarditis often occurs around the first or second dose of ICIs, checking troponin levels at baseline and each cycle may be of value, especially in high-risk patients, notably the elderly. An elevated value would warrant an urgent referral to cardiology for further evaluation, in the light of suspected ICI-induced myocarditis, potentially preventing a fatal outcome.

To date, discontinuation of ICIs and immunosuppression with glucocorticoids represent the cornerstone of the management of ICIM. The ASCO clinical practice guidelines for the management of irAE suggest the initiation of 1 mg/kg daily of either intravenous or oral prednisone or equivalent followed by a taper over 4–6 weeks [ 27 ]. Our patient was treated with 1 mg/kg per day of methylprednisolone followed by oral prednisone tapered over 6 weeks, which is in line with ASCO recommendations [ 27 ]. In the study of Mahmood et al. , most patients were treated with glucocorticoids with a mean time from admission to steroid initiation of 21.4 ± 16 h [ 7 ]. The median equivalent dose of methylprednisolone was 120 mg (range 0 to 1000 mg) and higher doses of steroids were associated with lower peak and discharge troponin levels and lower adverse cardiac events. Other immunosuppression therapies were also administered in a few cases including intravenous immunoglobulin, antithymocyte globulin, and infliximab [ 7 ]. According to the review by Palaskas et al. , re-initiation of ICI therapy is generally not recommended [ 23 ]. Patients should also be treated with conventional cardiac therapy, bradyarrhythmias, in particular advanced AV block, warrant temporary pacemaker insertion [ 23 ].

In conclusion, we report a rare case of pembrolizumab-induced myocarditis with complete atrioventricular block concomitant with myositis in a metastatic bladder cancer patient. As the spectrum of use of immune checkpoint inhibitors is continuing to rise, oncologists, cardiologists, emergency department physicians, pharmacists, and other specialists should be vigilant for this immune-related adverse event, particularly due to its early onset, challenging assessment and diagnosis, and fulminant progression. Troponin monitoring in high-risk patients, along with baseline TTE may help identify ICIM promptly.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Abbreviations

  • Immune checkpoint inhibitor

Cytotoxic T lymphocyte-associated antigen 4

Programmed cell death protein 1

Programmed cell death ligand 1

Immune-related adverse events

Immune checkpoint inhibitor-associated myocarditis

Atrioventricular

Electrocardiogram

Transthoracic echocardiogram

Left ventricular ejection fraction

Acetylcholine receptor binding antibodies

Major cardiac event

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Saad, R., Ghaddar, A. & Zeenny, R.M. Pembrolizumab-induced myocarditis with complete atrioventricular block and concomitant myositis in a metastatic bladder cancer patient: a case report and review of the literature. J Med Case Reports 18 , 107 (2024). https://doi.org/10.1186/s13256-024-04397-3

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    Free Google Slides theme and PowerPoint template. The heart is the central organ of the cardiovascular system. Currently, many people suffer from diseases of this system, fundamental in the functioning of the body. For this reason, it is important to talk about this type of diseases. If you want to make a presentation about cardiovascular ...

  21. Cardiovascular Disease Google Slides & PowerPoint template

    Cardiovascular Disease Presentation Free Google Slides theme and PowerPoint template It's time to talk about cardiovascular diseases. Provide some data about them using this creative template full of illustrations of hearts, body diagrams, tables.

  22. The Circulatory System PowerPoint

    This interactive PowerPoint covers the function of the circulatory system, advantages of double circulation, the structures of the heart and the structure and function of blood vessels. Activities and practice questions are included within the PowerPoint along with model answers. Recommended time: 2-4 lessons.

  23. Pembrolizumab-induced myocarditis with complete atrioventricular block

    Background The cardiovascular system is among the least systems affected by immune-related adverse events. We report a rare life-threatening case of pembrolizumab-induced myocarditis with complete atrioventricular block and concomitant myositis in a metastatic bladder cancer patient. Case presentation An 82-year-old Caucasian female with invasive urothelial carcinoma, started on first-line ...