Blood

Blood is a fluid connective tissue. It circulates around the body through the blood vessels by the pumping action of the heart. Arterial blood carries oxygen and nutrient to all the body’s cells, and venous blood carries carbon dioxide and other metabolic wastes away from the cells.

In addition to the transport of gases, nutrients, and wastes, blood has many other functions that include: • The removal of waste such as carbon dioxide, urea and lactic acid from the body tissues.
• The defense of the body against infection by microorganisms or parasites.
• The repair of damage to the body tissues.
• The transport of chemical messages, such as hormones and hormone-like substances.
• The control of body pH (the normal pH of blood is in the range of 7.35 - 7.45).
• The control of body temperature.

The Composition of Blood

Blood is a colloidal solution, it is made up of particles suspended in a fluid. It accounts for about 7% of the human body weight. The average adult has a blood volume of roughly 5 liters, composed of a fluid called plasma, and several kinds of cells. Within the blood plasma, are erythrocytes (red blood cells), leukocytes (white blood cells), thrombocytes (platelets) and other substances. The cells that make up the blood can be seen in Figure 1.

Figure 1: A scanning electron microscope (SEM) image of normal circulating human blood. One can see red blood cells, several white blood cells including knobby lymphocytes, a monocyte, a neutrophil, and many small disc-shaped platelets.

Plasma

Plasma is the golden-yellow liquid part of the blood. Plasma is 90% water and 10% dissolved materials including proteins, glucose, ions, hormones, and gases. It acts as a buffer, maintaining pH near 7.4. Plasma is about 54% the volume of blood; cells and fragments make up about 46% of the volume.

Red Blood Cells

Red blood cells, also known as erythrocytes, are flattened, doubly concave cells that carry oxygen. There are about 4 to 6 million cells per cubic millimeter of blood. Red blood cells make up about 45% of blood volume, as shown in Figure 2. Each red blood cell has 200 million hemoglobin molecules. Humans have a total of 25 trillion red blood cells (about 1/3 of all the cells in the body). Red blood cells are continuously made in the red marrow of long bones, ribs, skull, and vertebrae. Each red blood cell lives for only 120 days, after which they are destroyed in liver and spleen.

Figure 2: The components of blood. Red blood cells make up about 45% of the blood volume, white blood cells, about one percent, and platelets less than one percent. Plasma makes up the rest of the blood.

Mature red blood cells do not have a nucleus or other organelles. They contain the protein hemoglobin which gives blood its red color. The iron-containing heme portion of hemoglobin enables the protein to carry oxygen to cells. Heme binds to molecules of oxygen, which increases the ability of the blood to carry the gas.

Iron from hemoglobin is recovered and reused by red marrow. The liver degrades the heme units and secretes them as pigment in the bile, responsible for the color of feces. Each second two million red blood cells are produced to replace those thus taken out of circulation.

White Blood Cells

White blood cells, also known as leukocytes, are generally larger than red blood cells, as shown in Figure 3. They have a nucleus, but do not have hemoglobin. White blood cells make up less than one percent of the blood’s volume. They are made from stem cells in bone marrow. They function in the cellular immune response. There are five types of white blood cells. Neutrophils enter the tissue fluid by squeezing through capillary walls and phagocytizing (swallowing) foreign bodies. Macrophages also swallow and destroy cell debris and bacteria or viruses. In Figure 4, a macrophage is shown phagocytizing two particles, possibly pathogens. Macrophages also release substances that cause the numbers of white blood cells to increase. Antigen-antibody complexes are swallowed by macrophages. Lymphocytes fight infection. T-cells attack cells containing viruses. B-cells produce antibodies.

Figure 3: Relative sizes of red and white blood cells. a - red blood cells; b – neutrophil; c - eosinophil; d – lymphocyte. b, c, and d are different types of white blood cells.

Figure 4: Macrophage showing cytoplasmic extensions that allow it to “swallow” particles or pathogens. In the image here, a mouse macrophage stretches its arms to engulf two particles at once.

Platelets

Platelets, also known as thrombocytes, are important in blood clotting. Platelets are cell fragments that bud off bone marrow cells called megakaryocytes. A platelet is shown in Figure 5. They make up less than one percent of blood volume. Platelets carry chemicals essential to blood clotting. They change fibrinogen into fibrin, a protein that creates a mesh onto which red blood cells collect, forming a clot. This clot stops more blood from leaving the body and also helps to prevent bacteria from entering the body. Platelets survive for 10 days before being removed by the liver and spleen. There are 150,000 to 300,000 platelets in each milliliter of blood. Platelets stick to tears in blood vessels and they release clotting factors.

Figure 5: Cells of the blood. From left to right: Red blood cell, platelet, white blood cell. The concave side of red blood cells can be seen. Both sides of red blood cells are concave. The biconcave shape gives the red blood cells a smaller surface to volume ratio, which allows them to pick up large amounts of oxygen.

Other Blood Components

Blood plasma also contains other substances other than water. Some important components of blood include:

• Serum albumin: a plasma protein that acts as a transporter of hormones and other molecules.
• Antibodies: proteins that are used by the immune system to identify and destroy foreign objects such as bacteria and viruses.
• Hormones: chemical messengers that are produced by one cell and carried to another.
• Electrolytes such as sodium (Na+) and chloride (Cl-) ions.

Production and Breakdown of Blood Cells

Blood cells are produced in the red and yellow bone marrow in a process called hematopoiesis. Blood cells are broken down by the spleen and certain cells in the liver. The liver also clears some proteins, lipids and amino acids from the blood. The kidney actively secretes waste products of the blood into the urine.

Functions of Blood

Transport of Oxygen

The hemoglobin molecule is the major transporter of oxygen in mammals, including humans and many other species. About 98.5 percent of the oxygen in a sample of arterial blood in a healthy human is bonded with hemoglobin. Only 1.5 percent of the oxygen in blood is not carried by hemoglobin, instead it is dissolved in the plasma.

Under normal conditions in humans at rest, the hemoglobin in the red blood cells that are leaving the lungs is about 98 to 99 percent saturated with oxygen, and the blood is referred to as oxygenated. In a healthy adult at rest, deoxygenated blood returning to the lungs is still 75 percent saturated with oxygen. Oxygen saturation of arterial blood at or below 95 percent is considered dangerous in an individual at rest (for instance, during surgery under anesthesia)

Substances other than oxygen can bind to the hemoglobin; in some cases this can cause irreversible damage to the body. The gas carbon monoxide, for example, is very dangerous when absorbed into the blood. It bonds irreversibly with hemoglobin, which reduces the volume of oxygen that can be carried in the blood. Carbon monoxide poisoning can very quickly cause suffocation and death. Carbon monoxide is released during combustion (fire). It is released by cigarettes, barbeque grills, combustion of petrol products in cars and trucks, or anything else that can be burned.

Transport of Carbon Dioxide

When systemic arterial blood flows through capillaries, carbon dioxide diffuses from the tissues into the blood. Some carbon dioxide is dissolved in the blood. The remaining carbon dioxide is converted to bicarbonate and hydrogen ion which is then carried in the blood to the lungs, where it is converted back to carbon dioxide and released into the lungs.

Thermoregulation

Blood circulation transports heat through the body, and adjustments to this flow are an important part of thermoregulation. Increasing blood flow to the surface (e.g. during warm weather or strenuous exercise) causes warmer skin, resulting in greater heat loss. Decreasing surface blood flow conserves heat.

Blood Clotting

Coagulation, or blood clotting, is a complex process by which blood forms solid clots. Coagulation is important to stop bleeding and begin repair of damaged blood vessels. Blood clotting disorders can lead to an increased risk of bleeding or clotting inside a blood vessel. Platelets are important for the proper coagulation of blood.

Clotting is started almost immediately when an injury damages the endothelium of a blood vessel. Platelets clump together, forming a plug at the site of injury. Then, proteins in the plasma called coagulation factors, respond in a series of chemical reactions that form a tough protein called fibrin. The fibrin strands form a web across the platelet plug, trapping red blood cells before they can leave through the wound site. This mass of platelets, fibrin, and red blood cells forms a clot that hardens into a scab.

Certain nutrients are needed for the proper functioning of the clotting mechanism. Two of these are calcium and vitamin K. Luckily for you, bacteria that live in your intestines make enough vitamin K so you do not need to have extra in your food.

Blood Types

Blood type (also called a blood group), is determined by the presence or absence of certain molecules, called antigens, on the surface of red blood cells. An antigen is a molecule or substance that causes an immune response. Blood type antigens may be proteins, or carbohydrates, depending on the blood group system. The antigens on a person’s own body cells are recognized by their immune system as “self” antigens, and their immune system does not attack them. However, if a person is exposed to a blood group antigen that is different from their own blood group, the person’s immune system will produce antibodies against the donor blood antigens. These antibodies can bind to antigens on the surface of transfused red blood cells (or other tissue cells) often leading to destruction of the cells by the immune system.

The erythrocyte surface antigens that have one allele, or a group of very closely linked genes, are collectively called a ”blood group system”. There are 29 known blood group systems in humans, but the ABO blood group system and the Rhesus (Rh) blood group system are the most important for blood transfusions.

ABO Blood Group System

In 1875, a German physiologist, Leonard Landois reported that the blood cells of a human and an animal would clump together when mixed. In the early 1900s, Austrian biologist and physician Karl Landsteiner pointed out that a similar clumping reaction occurred when the blood of one person was transfused with another. He determined that this might be the cause of shock, jaundice, and release of hemoglobin that had followed some earlier attempts at person-to-person blood transfusions.

In 1909, Landsteiner classified blood into the A, B, AB, and O groups. He also showed that transfusions between of the same blood group did not result in the destruction of blood cells and that clumping occurred only when a person was transfused with the blood of a person belonging to a different blood group.

The ”A” and ”B” of the ABO blood group refer to two carbohydrate antigens found on the surface of red blood cells. There is not an O antigen. Type O red blood cells do not have either type A or B antigens on their surface, as listed in Table 1. Antibodies are found in the blood plasma. The blood type of a person can be determined by using antibodies that bind to the A or B antigens of red blood cells.

Agglutination is the clumping of red blood cells that occurs when different blood types are mixed together, shown in Figure 6. It involves a reaction between antigens on the surface of red blood cells and protein antibodies in the blood plasma. Mixing different blood types together can cause agglutination, a process that has been used as a way of determining a person’s blood type.

Figure 6: Antigens on the red blood cell surface. Antibodies attach to the antigens on the red blood cell, causing the blood cells to clump together. This leads to agglutination of the blood.

Rhesus Blood Group System

The Rhesus system is the second most significant blood group system in human blood transfusion. The most significant Rhesus antigen is called the RhD antigen, also called Rhesus factor. A person either has, or does not have the RhD antigen on the surface of their red blood cells. This is usually indicated by ”RhD positive” (does have the RhD antigen) or ”RhD negative” (does not have the antigen) suffix to the ABO blood group (see blood agglutination test in Figure 7).

Figure 7: A bedside blood grouping card showing the agglutination of the blood with anti-A and anti-Rh(D), but not with anti-B. Therefore the blood group is A positive. This method of blood grouping relies on seeing an agglutination reaction to determine a person’s blood group. The card has dried blood group antibody reagents fixed onto its surface. A drop of the person’s blood is placed on each area on the card. The presence or absence of visual agglutination allows a quick method of determining the ABO and Rhesus group of the person.

The Rhesus system is named after the Rhesus monkey, in which the antigen was first discovered by Karl Landsteiner and Alexander S. Wiener in 1937. The importance of the Rh factor was realized soon after. Dr. Phillip Levine, a pathologist who worked at a New York hospital, made the connection between the Rh factor and the incidence of a blood disease in newborn babies. The disease, called hemolytic disease of the newborn is a condition that develops while the fetus is in the womb. If a mother is RhD negative, and the father is RhD positive, the fetus may inherit the dominant RhD positive trait from the father. The RhD negative mother can make antibodies against the RhD antigens of her developing baby. This can happen if some of the fetus’ blood cells pass into the mother’s blood circulation, or if the mother has received an RhD positive blood transfusion.

The fetus’ red cells are broken down and the fetus can develop anemia. This disease ranges from mild to very severe, and fetal death from heart failure can occur. Most RhD disease can be prevented by treating the mother during pregnancy or soon after childbirth. The mother is injected with anti-RhD antibodies, so that the baby’s red blood cells are destroyed before her body can produce antibodies against them. If a pregnant woman is known to have anti-RhD antibodies, the RhD blood type of a fetus can be tested by analysis of fetal DNA in maternal plasma to assess the risk to the fetus of Rh disease.

The presence or absence of the ABO group antigens and the RhD antigens are always determined for all recipient and donor blood. Figure 7 shows a routine way in which a person’s ABO blood group is determined.

Blood Products

In order to provide maximum benefit from each blood donation and to extend shelf-life, blood banks separate some whole blood into several different products. Some of the most common of these products are packed red blood cells, plasma, platelets, and fresh frozen plasma. Units of packed red blood cells are made by removing as much of the plasma as possible from whole blood units. Clotting factors made by genetic engineering are now routinely used for the treatment of the clotting disorder hemophilia, so the risk of possible infection from donated blood products is avoided.

Universal Donors and Universal Recipients

Regarding the donation of packed red blood cells, individuals with type O negative blood are often called universal donors, and those with type AB positive blood are called universal recipients. Type O red blood cells do not have the A or B antigens, and can be given to people with a different ABO blood group. The blood plasma of an AB person does not contain any anti-A or anti-B antibodies, so they can receive any ABO blood type. The possible reactions of anti-A and anti-B antibodies in the donor blood to the recipient’s red blood cells are usually not a problem because only a small volume of plasma that containing antibodies is given to the recipient. Refer to Table 1 for a complete listing of ABO antigens and antibodies that are involved in the ABO system.

In April 2007 researchers discovered a way to convert blood types A, B, and AB to O; the method used enzymes that removed the antigens on the surface of the red blood cells.

Other Blood Group Systems

You probably have heard a lot about the ABO and Rhesus (RhD) blood group systems by now, but you have probably not heard much about the other 27 other systems. Many other antigens are found on the cell membrane of red blood cells. For example, an individual can be AB RhD positive, and at the same time M and N positive (MNS system), K positive (Kell system), \(Le^a\) or \(Le^b\) negative (Lewis system), Duffy positive, or Duffy negative (Duffy system), and so on, being positive or negative for each blood group system antigen. Many of the blood group systems were named after the patients in whom the antibodies were first found.

Some blood group systems are associated with a disease, for example, the Kell antigen is associated with McLeod syndrome, a genetic disorder in which the red blood cells are spiky shaped. Certain other blood group systems may affect resistance to infections, an example being the resistance to specific malaria species seen in individuals who lack the Duffy antigen. The Duffy antigen is less common in ethnic groups from areas with a high incidence of malaria.

Rare blood types can cause supply problems for blood banks and hospitals. For example Duffy-negative blood occurs much more frequently in people of African origin, and the rarity of this blood type in the rest of the population can result in a shortage of Duffy-negative blood. Similarly, for RhD negative people, there is a risk associated with traveling to parts of the world where supplies of RhD negative blood are rare, particularly East Asia.

Homeostatic Imbalances of the Blood

Problems can occur with red blood cells, white blood cells, platelets, and other components of the blood. Many blood disorders are genetic, they are inherited from a parent, some are a result of nutrient deficiency, while others are cancers of the blood.

Sickle-cell disease is a group of genetic disorders caused by abnormally shaped hemoglobin, called sickle hemoglobin. In many forms of the disease, the red blood cells change shape because the abnormal hemoglobin proteins stick to each other, causing the cell to get a rigid surface and sickle shape, shown in Figure 8. This process damages the membrane of the red blood cell, and can cause the cells to get stuck in blood vessels. This clotting causes oxygen starvation in tissues, which may cause organ damage such as stroke or heart attack. The disease is chronic and lifelong. Individuals are most often well, but their lives are punctuated by periodic painful attacks. Sickle-cell disease occurs more commonly in people (or their descendants) from parts of the world such as sub-Saharan Africa, where malaria is or was common. It also occurs in people of other ethnicities. As a result, those with sickle cell disease are resistant to malaria since the red blood cells are not favored by the malaria parasites. The mutated hemoglobin allele is recessive, meaning it must be inherited from each parent for the individual to have the disease.

Figure 8: Sickle-cell disease. The abnormal shape of the red blood cells damages the red blood cells which causes them to get stuck in blood vessels. The blocked capillaries reduce the blood flow to an organ, and can result in pain and organ damage.

Iron deficiency anemia is the most common type of anemia. It occurs when the dietary intake or absorption of iron is less than what is needed by the body. As a result, hemoglobin, which contains iron, cannot be made. In the United States, 20 percent of all women of childbearing age have iron deficiency anemia, compared with only 2 percent of adult men. The principal cause of iron deficiency anemia in premenopausal women is blood lost during menstruation.

Leukemia is a cancer that originates in the bone marrow and is characterized by an abnormal production of white blood cells (rarely red blood cells) that are released into the bloodstream. Lymphoma is a cancer of the lymphatic system, which helps to filter blood. Lymphoma can be categorized as either Hodgkin’s lymphoma or non-Hodgkin’s lymphoma.

Hemophilia is the name of a group of hereditary genetic diseases that affect the body’s ability to control blood clotting. Hemophilia is characterized by a lack of clotting factors in the blood. Clotting factors are needed for a normal clotting process. When a blood vessel is injured, a temporary scab does form, but the missing coagulation factors prevent the formation of fibrin which is needed to maintain the blood clot. Therefore, a person who has hemophilia is initially able to make a clot to stop the bleeding, but because fibrin is not produced, the body is unable to maintain a clot for long. The risks of the re-bleeding of an injury and internal bleeding are increased in hemophilia, especially into muscles, joints, or bleeding into closed spaces.

Haemochromatosis is a hereditary disease that is characterized by a buildup of iron in the body. Iron accumulation can eventually cause end organ damage, most importantly in the liver and pancreas, manifesting as liver failure and diabetes mellitus respectively. It is estimated that roughly one in every 300-400 people is affected by the disease, primarily of Northern European and especially people of Irish, Scottish, Welsh and English descent.