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Production of red blood cells occurs in the red bone marrow, and is stimulated by erythropoietin, EPO. EPO is secreted predominantly by the kidneys. The kidneys sense oxygen levels in the blood and adjust EPO secretion accordingly to the body’s needs.
Red cells live about 100 to 120 days. With age, the cells lose their elasticity. Without protein synthesis, they are unable to repair themselves. Worn-out red cells are detected in the spleen, which serves as a quality control center. The spleen has a network of very narrow channels which test the agility of erythrocytes. Healthy cells can bend and fold to squeeze through, while old cells, being rigid and fragile, get stuck and are destroyed by macrophages. Parts of the dead cells are salvaged to make new cells. Part of the heme is secreted into bile and disposed in feces.
The number of red blood cells is strictly regulated and has important clinical significance. Common measurements include red blood cell count, hematocrit, and hemoglobin concentration.
An imbalance between the rate of red cell production and death can result in their deficiency, known as anemia, or excess, known as polycythemia.
Anemia can be caused by blood loss, insufficient erythrocyte production, or their premature destruction.
Insufficient red cell production can result from:
+ deficiency of any of the nutrients that are required for their formation,
+ impaired kidney function, which leads to lower secretion of EPO,
+ or destruction of the bone marrow tissue responsible for red cell production. This can happen because of inherited mutations, autoimmune diseases, or exposure to chemicals, drugs or radiation; but causes are unknown for many cases. Reduced erythropoiesis is known as hypoplastic anemia, while complete cessation of red cell production is called aplastic anemia.
Inappropriate destruction of red blood cells, also called hemolytic anemia, can be inherited or acquired. The inherited forms are usually due to defects within red cells themselves, such as abnormalities in hemoglobin structure, while acquired hemolytic anemia can be caused by toxins, drugs, autoimmune diseases, infection, overactive spleen, or blood group mismatch.
Anemia results in low oxygen levels in the blood, known as hypoxemia. Mild anemia causes weakness and confusion, while severe anemia may lead to organ failure due to lack of oxygen and is life-threatening.
Excess red cell production, or polycythemia, can be primary or secondary. Primary polycythemia, or polycythemia vera, is a form of blood cancer, where the bone marrow produces too many blood cells. Secondary polycythemia, on the other hand, is a consequence of low oxygen state, which induces the kidneys to produce more erythropoietin, subsequently leading to more erythrocytes. Causes include smoking, air pollution, emphysema, living at high altitudes, and physical strenuous conditioning in athletes.
Excess red cells may increase blood volume, blood pressure, and viscosity. This augments the risks for blood clot formation, which may lead to heart attacks, strokes, and pulmonary embolism. The heart also has to work harder to manage larger amount of thicker blood and heart failures may result.

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Red blood cells, also called erythrocytes, are the predominant cell type in the blood. They are responsible for transport of oxygen from the lungs to body’s tissues, and removal of carbon dioxide in the reverse direction. Erythrocytes lack most of typical cell structures, they have no nucleus, and almost no organelles. This means they cannot regenerate, cannot synthesize new proteins, and cannot use the oxygen they are carrying. Erythrocytes are shaped almost like a donut, with biconcave surfaces. This unique shape increases the cell’s surface area for efficient gas exchange, while also being flexible to change when needed. Red cells contain structural proteins actin and spectrin, which make them resilient but also elastic, like pieces of memory foam. This elasticity, together with the donut shape, enables the cells to bend and fold on themselves, to squeeze through narrow capillaries, then spring back to their original shape in larger vessels.
The major component of red blood cells is a protein named hemoglobin. Hemoglobin is composed of four polypeptide chains, each of which is bound to a red pigment molecule called heme. Heme binds oxygen to a ferrous iron in its center. Thus, a molecule of hemoglobin can bind up to four molecules of oxygen. Binding of oxygen is a cooperative process: binding at one site changes the protein conformation in a way that facilitates further binding at other sites. Formation of the hemoglobin-oxygen complex, known as oxyhemoglobin, is reversible, depending on oxygen partial pressure. Oxygen binds in the lungs where its pressure is high, and disassociates in tissues, where its pressure is low.
While hemoglobin is responsible for transport of most of the oxygen, it only carries a small portion of carbon dioxide. Carbon dioxide binds to the polypeptide part of hemoglobin, and not the heme, but its binding changes the conformation of the molecule and decreases its affinity for oxygen. In other words, the two gases compete for binding on hemoglobin; oxygen binding is favored in the lungs, while carbon dioxide binding is more favorable in tissues.
The majority of carbon dioxide is transported in the blood in the form of bicarbonate ions. Conversion of carbon dioxide to carbonic acid, which dissociates into bicarbonate and hydrogen ions, is catalyzed by an enzyme present in red blood cells, called carbonic anhydrase. Bicarbonate ions then diffuse out to the plasma to be exchanged for chloride ions, while hydrogen ions bind to hemoglobin that has released oxygen.
When red blood cells reach the lungs, the reverse happens: high oxygen pressure favors its binding to hemoglobin, which releases hydrogen ions and carbon dioxide; the same carbonic anhydrase then converts bicarbonate and hydrogen ions back to carbon dioxide to be breathed out.

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Mature blood cells have a limited lifespan and must be continuously replaced through a process called hematopoiesis, which starts in the red bone marrow. All formed elements of the blood derive from a common progenitor – the hematopoietic stem cells, HSCs. HSCs are multipotent, meaning they can differentiate to all types of blood cells. They also have the ability to multiply constantly to maintain their numbers in the bone marrow. Formation of blood cells from hematopoietic stem cells is a multi-step process, involving several intermediate progenitors, and is regulated by a network of signaling molecules, known as cytokines. These cytokines control the proliferation, differentiation and survival or death of the various progenitors. By doing so, they maintain steady-state levels of blood cells in normal situations; and, in response to certain stimuli, induce production of a particular cell type. For example, in response to blood loss, production of red blood cells is accelerated.
Differentiation starts when progenitor cells develop surface receptors for a specific stimulating factor. Once this happened, the cells lose their potency and become committed to a certain cell type.
Production of red blood cells, RBC, or erythrocytes, is stimulated by erythropoietin, EPO. During the differentiation process, the cells reduce in size, increase in number, start making hemoglobin, and lose their nucleus. EPO is produced predominantly by the liver during fetal development and by the kidneys in adulthood. Low levels of EPO are constitutively secreted and are sufficient to compensate for normal red blood cell turnover. When RBC count drops, such as during blood loss, the resulting oxygen-deficiency state, hypoxemia, is detected by the kidneys. The kidneys respond by increasing their EPO secretion, which leads to increased red blood cell production by the end of 3 to 5 days. People living at high altitudes usually have higher RBC count as a response to lower oxygen levels. Athletes whose demand for oxygen is more elevated, also have higher RBC counts.
Production of granulocytes and macrophages, the key players of the body’s innate immune response, is controlled by several colony-stimulating factors, CSFs. Normally, these cells are kept at a more or less constant number, by relatively low levels of CSFs, but their production can increase greatly and quickly upon infection. CSFs are commonly secreted by mature lymphocytes and macrophages, but can be produced, if needed, by virtually any organ or cell type. CSF production may increase a thousand-fold in response to indicators of infection, such as bacterial endotoxins.
Production of platelets is stimulated by thrombopoietin, TPO, a hormone secreted by the kidneys and liver. TPO is responsible for formation of megakaryocytes – the gigantic cells that develop as a result of multiple rounds of DNA replication without cell division. A megakaryocyte gives rise to tens of thousands of platelets, which are essentially broken fragments of its cytoplasm. Production of platelets is subject to a classic negative feedback loop: reduced platelet levels in the blood promote their production, while elevated levels inhibit it.

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The cardiovascular system is part of the circulatory system that circulates blood. The circulatory system also includes the lymphatic system, which circulates lymph, but the terms circulatory system and cardiovascular system are commonly used interchangeably to describe blood circulation.
The cardiovascular system consists of the heart, blood, and blood vessels. The heart is essentially a pump that moves blood through the vessels. It has 2 sides, each of which has 2 chambers.
The best-known function of the circulatory system is perhaps the transport of inhaled oxygen from the lungs to body’s tissues, and removal of carbon dioxide in the opposite direction to be exhaled. Basically, oxygen-poor blood from the body returns to the right side of the heart, where it is pumped to the lungs. In the lungs, blood picks up oxygen and releases carbon dioxide. Oxygen-rich blood then returns to the left side of the heart. This part of the system is called the pulmonary circuit.
The left side of the heart pumps oxygen-rich blood to body’s tissues, where it unloads oxygen and picks up carbon dioxide. The resulting deoxygenated blood again returns to the heart’s right side to complete the cycle. This part is the systemic circuit. Because the heart’s left side has to pump blood to the entire body, it has much thicker muscle than the right side.
There are 4 valves which serve to ensure one-way blood flow through the heart: oxygen-poor blood flows from right atrium to right ventricle to pulmonary arteries; while oxygen-rich blood moves from left atrium to left ventricle to the aorta.
The heart is enclosed in a double-walled protective sac called the pericardium. The pericardial cavity contains a fluid which serves as lubricant and allows the heart to contract and relax with minimum friction. The heart wall has 3 layers:
– the outer layer, epicardium, lines the pericardial cavity,
– the inner layer, endocardium, lines heart chambers and valves and is continuous with the endothelium of blood vessels,
– and the thick middle layer, myocardium, is the muscle tissue responsible for the beating of the heart.
The contraction of the heart muscle is initiated by electrical impulses, known as action potentials. Unlike skeletal muscles, which have to be stimulated by the nervous system, the heart generates its own electrical stimulation. The impulses start from a small group of cells called the pacemaker cells, which constitute the cardiac conduction system. The primary pacemaker is the SA node, it initiates all heartbeats and controls heart rate.
Apart from transporting gases, the blood also supplies body’s tissues with nutrients and removes metabolic wastes. It receives nutrients from the digestive system, where digested substances are absorbed through the walls of the small intestine into the bloodstream. These substances are then passed through the liver to be screened for toxins before joining the general circulation. In tissues, nutrients are exchanged for wastes. Wastes are then filtered from the blood in the kidneys and removed in urine.
The blood also carries hormones from endocrine glands to target organs, and plays an important role in the body’s immune defense.
The blood has two main components: a clear extracellular fluid called plasma, and the so-called formed elements which include red blood cells, white blood cells and platelets. Red blood cells transport oxygen and carbon dioxide; white blood cells participate in various defense mechanisms against invading organisms; while the platelets are responsible for blood clotting, minimizing blood loss during an injury.
The blood circulatory system is a closed loop, meaning the blood itself never leaves the vessels. Instead, substances diffuse through the walls of blood vessels to move to and from the surrounding tissues.
Vessels that move blood away from the heart are called arteries, while those that bring blood back to the heart are veins. Arteries usually carry oxygenated blood while veins carry deoxygenated blood. For pulmonary arteries and veins, however, the reverse is true.
The usual route of blood flow is: heart to large arteries, smaller arteries, then even smaller arteries, called arterioles, then smallest blood vessels called capillaries, where the exchange of substances takes place. Blood then collects into small veins, called venules, then to larger veins and back to the heart.
Arteries and veins essentially serve to conduct blood, their walls consist of 3 layers:
– an outer layer of loose connective tissue serves to anchor the vessels to the surroundings.
– a middle layer of mostly smooth muscles allows the vessels to constrict or dilate, regulating blood flow.
– and an inner layer consisted of thin squamous endothelium, separated from outer layers by a basal membrane.
In general, larger vessels have more connective tissue and smooth muscle. In addition, arteries have more muscles than veins because they carry blood away from the heart and must withstand higher pressures generated by the beating of the heart.
The walls of capillaries, whose function is to exchange substances between the blood and surrounding tissue, consist solely of a thin endothelium with its basement membrane, thus permitting easy diffusion of blood solutes.

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Premature atrial contractions, PACs, are premature heartbeats originating in one of the upper chambers of the heart, the atria. PACs are common among patients with lung disorders, such as chronic obstructive pulmonary disease, COPD, but they also often occur in healthy people. PACs may be caused or worsened by caffeine, alcohol use, and certain medications. Apart from occasional palpitations, PACs are generally asymptomatic and do not require treatment in otherwise healthy people.
A PAC happens when the atria are activated by an ectopic site in an atrium, instead of the SA node. Because atrial depolarization is initiated outside the SA node, the associated P wave has an unusual, non-sinus morphology. An early atrial activation may cause the P wave to merge with the preceding T wave producing a peaked fusion wave. In situations where the ectopic site is located near the AV node, the atria are depolarized mainly by retrograde conduction and the resulting P wave is inverted; the PR interval representing the time the signal reaches the AV node, is slightly shorter. An ectopic atrial activation can usually enter the SA node, depolarize it and reset its timing, causing a so-called non-compensatory pause. On an ECG, this is seen as changes in the PP intervals that contain the ectopic beats. This feature can be used to differentiate PACs from ectopic beats of ventricular origin, PVCs. PVCs typically do NOT conduct back to the atria, SA node firing is NOT affected, and PP interval remains unchanged.
The downstream ventricular conduction of a PAC can be normal, aberrant or absent. In most cases, conduction through the AV node and ventricles is not affected, resulting in a normal narrow QRS complex. Occasionally however, ventricular conduction may be aberrant, causing a widened QRS complex, usually with right bundle branch block morphology, which may look similar to a premature beat of ventricular origin. In this case, differentiation is made based on the presence of a preceding P wave and a non-compensatory pause in PAC.
A non-conducted PAC is one that arrives too early to the AV node, at the time when the AV node is still in refractory period and thus cannot be activated.