The average human adult has more than 5 liters (6 quarts) of blood in his or herbody. Blood carries oxygen and nutrients to living cells and takes away their wasteproducts. It also delivers immune cells to fight infections and contains plateletsthat can form a plug in a damaged blood vessel to prevent blood loss.
Through the circulatory system, blood adapts to the body's needs. When you areexercising, your heart pumps harder and faster to provide more blood and henceoxygen to your muscles. During an infection, the blood delivers more immune cells tothe site of infection, where they accumulate to ward off harmful invaders.
All of these functions make blood a precious fluid. Each year in the USA, 30 millionunits of blood components are transfused to patients who need them. Blood is deemedso precious that is also called "red gold" because the cells and proteins itcontains can be sold for more than the cost of the same weight in gold.
This chapter introduces the components of blood.
Blood contains cells, proteins, and sugars
If a test tube of blood is left tostand for half an hour, the blood separates into three layers as the densercomponents sink to the bottom of the tube and fluid remains at the top.
The straw-colored fluid that forms the top layer is called plasma and forms about 60%of blood. The middle white layer is composed of white blood cells (WBCs) andplatelets, and the bottom red layer is the red blood cells (RBCs). These bottom twolayers of cells form about 40% of the blood.
Plasma is mainly water, but it also contains many important substances such asproteins (albumin, clotting factors, antibodies, enzymes, and hormones), sugars(glucose), and fat particles.
All of the cells found in the blood come from bone marrow. They begin their life asstem cells, and they mature into three main types of cells— RBCs, WBCs,and platelets. In turn, there are three types of WBC—lymphocytes,monocytes, and granulocytes—and three main types of granulocytes(neutrophils, eosinophils, and basophils). See them in action in "Meet the blood cells".
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Meet the blood cells.
See a figure of all the cellular elements of blood in Janeway & Traver's Immunobiology
A sample of blood can be further separated into its individual components by spinningthe sample in a centrifuge. The force of the spinning causes denser elements tosink, and further processing enables the isolation of a particular protein or theisolation of a particular type of blood cell. With the use of this method,antibodies and clotting factors can be harvested from the plasma to treat immunedeficiencies and bleeding disorders, respectively. Likewise, RBCs can be harvestedfor blood transfusion.
Red blood cells transport oxygen
Every second, 2-3 million RBCs areproduced in the bone marrow and released into the circulation. Also known aserythrocytes, RBCs are the most common type of cell found in the blood, with eachcubic millimeter of blood containing 4-6 million cells. With a diameter of only 6µm, RBCs are small enough to squeeze through the smallest blood vessels.They circulate around the body for up to 120 days, at which point the old or damagedRBCs are removed from the circulation by specialized cells (macrophages) in thespleen and liver.
In humans, as in all mammals, the mature RBC lacks a nucleus. This allows the cellmore room to store hemoglobin, the oxygen-binding protein, enabling the RBC totransport more oxygen. RBCs are also biconcave in shape; this shape increases theirsurface area for the diffusion of oxygen across their surfaces. In non-mammalianvertebrates such as birds and fish, mature RBCs do have a nucleus.
See an electron micrograph of red blood cells in Albert's
Molecular Biology of the Cell
If a patient has a low level of hemoglobin, a condition called anemia, they mayappear pale because hemoglobin gives RBCs, and hence blood, their red color. Theymay also tire easily and feel short of breath because of the essential role ofhemoglobin in transporting oxygen from the lungs to wherever it is needed around thebody.
White blood cells are part of the immune response
WBCs come in many different shapes and sizes. Some cells have nuclei with multiplelobes, whereas others contain one large, round nucleus. Some contain packets ofgranules in their cytoplasm and so are known as granulocytes.
See an electron micrograph of white blood cells in Albert's
Molecular Biology of the Cell
Despite their differences in appearance, all of the various types of WBCs have a rolein the immune response. They circulate in the blood until they receive a signal thata part of the body is damaged. Signals include interleukin 1 (IL-1), a moleculesecreted by macrophages that contributes to the fever of infections, and histamine,which is released by circulating basophils and tissue mast cells, and contributes toallergic reactions. In response to these signals, the WBCs leave the blood vessel bysqueezing through holes in the blood vessel wall. They migrate to the source of thesignal and help begin the healing process.
Individuals who have low levels of WBCs may have more and worse infections. Dependingupon which WBCs are missing, the patient is at risk for different types ofinfection. For example, macrophages are especially good at swallowing bacteria, anda deficiency in macrophages leads to recurrent bacterial infections. In contrast, Tcells are particularly skilled in fighting viral infections, and a loss of theirfunction results in an increased susceptibility to viral infections.
Neutrophils digest bacteria
Neutrophils are also known aspolymorphonuclear cells because they contain a nucleus whose shape (morph) isirregular and contains many (poly) lobes. They also belong to a group of WBCsknown as granulocytes because their cytoplasm is dotted with granules thatcontain enzymes that helps them digest pathogens.
See a neutrophil phagocytose a bacterium in Albert's
Molecular Biology of the Cell
Monocytes become macrophages
Monocytes are young WBCs thatcirculate in the blood. They develop into macrophages after they have left theblood and migrated into tissue. There they provide an immediate defense becausethey can engulf (phagocytose) and digest pathogens before other types of WBCsreach the area.
In the liver, tissue macrophages are called Kupffer cells, and they specialize inremoving harmful agents from blood that has left the gut. Alveolar macrophagesare in the lungs and remove harmful agents that may have been inhaled.Macrophages in the spleen remove old or damaged red blood cells and plateletsfrom the circulation.
See a macrophage phagocytose a red blood cell in Albert's
Molecular Biology of the Cell
Macrophages are also "antigen-presenting cells", presenting the foreign proteins(antigens) to other immune cells, triggering an immune response.
Lymphocytes consist of B cells and T cells
Lymphocytes are round cells thatcontain a single, large round nucleus. There are two main classes of cells, theB cells that mature in the bone marrow, and the T cells that mature in thethymus gland.
See an electron micrograph of a B cell and T cell in Albert's
Molecular Biology of the Cell
Once activated, the B cells and T cells trigger different types of immuneresponse. The activated B cells, also known as plasma cells, produce highlyspecific antibodies that bind to the agent that triggered the immune response. Tcells, called helper T cells, secrete chemicals that recruit other immune cellsand help coordinate their attack. Another group, called cytotoxic T cells,attacks virally infected cells.
Platelets help blood to clot
Platelets are irregularly shapedfragments of cells that circulate in the blood until they are either activated toform a blood clot or are removed by the spleen. Thrombocytopenia is a condition oflow levels of platelets and carries an increased risk of bleeding. Conversely, ahigh level of platelets (thrombocythemia) carries an increased risk of forminginappropriate blood clots. These could deprive essential organs such as the heartand brain, of their blood supply, causing heart attacks and strokes, respectively.
A diagram of a platelet in Albert's
Molecular Biology of the Cell
As with all the cells in the blood, platelets originate from stem cells in the bonemarrow. The stem cells develop into platelet precursors (called megakaryocytes) that"shed" platelets into the bloodstream. There, platelets circulate for about 9 days.If they encounter damaged blood vessel walls during this time, they stick to thedamaged area and are activated to form a blood clot. This plugs the hole. Otherwise,at the end of their life span they are removed from the circulation by the spleen.In a diverse number of diseases where the spleen is overactive, e.g. rheumatoidarthritis and leukemia, the spleen removes too many platelets, leading to increasedbleeding.
Your complete blood count
A complete blood count (CBC) is a simple blood test that is commonly ordered as partof a routine medical assessment. As the name suggests, it is a count of thedifferent types of cells found in the blood. The test can diagnose and monitor manydifferent diseases, such as anemia, infection, inflammatory diseases, andmalignancy. Table 1 gives an example ofCBC values, but note that the reference ranges and the units used may differ,depending upon the laboratory that carried out the test.
Table 1
Complete blood count.
Red blood cell count detects anemia
A CBC measures the following features of RBCs:
the total amount of hemoglobin (Hb) in the blood
the number of RBCs (RBCs)
the average size of a RBC (MCV)
the amount of space RBCs take up in the blood (hematocrit)
The CBC also includes information about RBCs that is calculated from the othermeasurements, e.g., the amount (MCH) and concentration (MCHC) of hemoglobin inRBCs.
The number of RBCs and the amount of hemoglobin in the blood are lower in womenthan in men. This is because of the menstrual loss of blood each month. Below acertain level of hemoglobin, a patient is said to be anemic, suggesting aclinically significant drop in oxygen carrying capacity. Anemia is not adiagnosis but a symptom of an underlying disease that has to be investigated.
A clue to the cause of anemia is the average size of RBC (mean corpuscularvolume, MCV). Causes of a high MCV include a deficiency of B12 orfolate vitamins in the diet. B12 is found in red meat therefore, adeficiency of B12 is especially common in vegetarians and vegans.Conversely, folate is plentiful in fresh leafy green vegetables, therefore, adeficiency of folate is common in the elderly, who may have a poor diet.
Low MCV anemia is common and may be a result of hereditary blood disorders, suchas thalassemia, but is most often caused by a deficiency of iron. For example,women of reproductive age may lose too much iron through heavy menstrualbleeding and are prone to this form of anemia, known as iron-deficiency anemia.
Hematocrit is the percentage of RBCs in relation to the total volume of blood
The hematocrit measures the fraction of the blood that is made up of RBCs. Itreflects the combination of the total number of RBCs, and the volume that theyoccupy.
One of the changes seen in pregnancy is a drop in hematocrit. This occurs becausealthough the production of RBCs does not change greatly, the plasma volumeincreases, i.e., the RBCs are "diluted". Alternatively, a low hematocrit canreflect a drop in RBC production by the bone marrow. This may be attributable tobone marrow disease (damage by toxins or cancer) or due to a decrease inerythropoietin, a hormone secreted by the kidney that stimulates RBC production.Decreased RBCs may also be the result of a reduced life span of the RBCs (e.g.,chronic bleeding).
A high hematocrit value may truly reflect an increase in the fraction of RBCs(e.g., increased erythropoietin attributable to a tumor of RBCs calledpolycythemia rubra vera), or it may reflect a drop in the plasma component ofthe blood (e.g., fluid loss in burn victims).
The number of WBCs increases in infection and tumors
The WBC count is a count of the number of WBCs found in one cubic millimeter ofblood.
An increased number of WBCs is most commonly caused by infections, such as aurinary tract infection or pneumonia. It may also be caused by WBC tumors, suchas leukemia.
A decreased number of WBCs is caused by the bone marrow failing to produce WBCsor by an increased removal of WBCs from the circulation by a diseased liver oran overactive spleen. Bone marrow failure may be caused by toxins or by thenormal bone marrow cells being replaced by tumor cells.
The WBC differential part of the CBC breaks down the WBCs into five differenttypes: neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Findingout the count of each type of WBC gives more information about the underlyingproblem. For example, in the early stages of an infection, most of the increasein WBCs is attributable to the increase in neutrophils. As the infectioncontinues, lymphocytes increase. Worm infections can trigger an increase ineosinophils, whereas allergic conditions, such as hay fever, trigger an increasein basophils.
The number of platelets indicates whether bleeding or clotting is likely
Normally, one cubic millimeter of blood contains between 150,000 and 400,000platelets. If the number drops below this range, uncontrolled bleeding becomes arisk, whereas a rise above the upper limit of this range indicates a risk ofuncontrolled blood clotting.
Hemoglobin binds oxygen
Hemoglobin is the oxygen-carrying protein that is found within all RBCs. It picks upoxygen where it is abundant (the lungs) and drops off oxygen where it is neededaround the body. Hemoglobin is also the pigment that gives RBCs their red color.
Heme groups and globins
As its name suggests, hemoglobin is composed of "heme" groups (iron-containingrings) and "globins" (proteins). In fact, hemoglobin is composed of four globinproteins—two alpha chains and two beta chains—each witha heme group. The heme group contains one iron atom, and this can bind onemolecule of oxygen. Because each molecule of hemoglobin contains four globins,it can carry up to four molecules of oxygen.
See hemoglobin structure in Albert's
Molecular Biology of the Cell
Hemoglobin transports oxygen
In the lungs, a hemoglobin molecule is surrounded by a high concentration ofoxygen, therefore, it binds oxygen. In active tissues, the oxygen concentrationis lower, so hemoglobin releases its oxygen.
This behavior is much more effective because thehemoglobin––oxygen binding is "co-operative". This meansthat the binding of one molecule of oxygen makes it easier for the binding ofsubsequent oxygen molecules. Likewise, the unbinding of oxygen makes it easierfor other oxygen molecules to be released. This means that the response ofhemoglobin to the oxygen needs of active tissues is much quicker.
Aside from the oxygen saturation of hemoglobin, other factors that influence howreadily hemoglobin binds oxygen include plasma pH, plasma bicarbonate levels,and the pressure of oxygen in the air (high altitudes in particular).
The molecule 2,3-disphosphoglycerate (2,3-DPG ) binds to hemoglobin and lowersits affinity for oxygen, thus promoting oxygen release. In individuals who havebecome acclimatized to living at high altitudes, the level of 2,3-DPG in theblood increases, allowing the delivery of more oxygen to tissues under lowoxygen tension.
Fetal hemoglobin
Fetal hemoglobin differs from adult hemoglobin in that it contains two gammachains instead of two beta chains. Fetal hemoglobin binds oxygen with a muchgreater affinity than adult hemoglobin; this is an advantage in the womb becauseit allows fetal blood to extract oxygen from maternal blood, despite its lowconcentration of oxygen.
Normally, all fetal hemoglobin is replaced by adult hemoglobin by the time ofbirth.
Breaking down hemoglobin
Old or damaged RBCs are removed from the circulation by macrophages in the spleenand liver, and the hemoglobin they contain is broken down into heme and globin.The globin protein may be recycled, or broken down further to its constituentamino acids, which may be recycled or metabolized. The heme contains preciousiron that is conserved and reused in the synthesis of new hemoglobin molecules.
During its metabolism, heme is converted to bilirubin, a yellow pigment that candiscolor the skin and sclera of the eye if it accumulates in the blood, acondition known as jaundice. Instead, the plasma protein albumin binds tobilirubin and carries it to the liver, where it is secreted in bile and alsocontributes to the color of feces.
Jaundice is one of the complications of an incompatible blood transfusion. Thisoccurs when the recipient's immune system attacks the donor RBCs as beingforeign. The rate of RBC destruction and subsequent bilirubin production canexceed the capacity of the liver to metabolize the bilirubin produced.
Hemoglobinopathies
Hemoglobinopathies form a group of inherited diseases that are caused bymutations in the globin chains of hemoglobin. Sickle cell anemia is the mostcommon of these and is attributable to a mutation that changes one of the aminoacids in the hemoglobin beta chain, producing hemoglobin that is "fragile". Whenthe oxygen concentration is low, RBCs tend to become distorted and "sickle"shaped. These deformed cells can block small blood vessels and damage the organsthey are supplying. This can be very painful, and if not treated, a sickle cellcrisis can be fatal.
Sickle cell anemia in Genes and Disease
Another inherited anemia that particularly affects individuals of Mediterraneandescent is thalassemia. A fault in the production of either alpha or beta globinchains causes a range of symptoms, depending on how many copies of the alpha andbeta genes are affected. Some individuals may be carriers of the disease andhave no symptoms, whereas if all copies of the genes are lost, the disease isfatal.
Thalassemia in Genes and Disease
The porphyrias are a group of inherited disorders in which the synthesis of hemeis disrupted. Depending upon the stage at which the disruption occurs, there area range of neurological and gastrointestinal side effects. King George III ofEngland ("the madness of King George") was one of the most famous individualswho suffered from porphyria.
Porphyria in Genes and Disease
Resources
KarlLandsteiner, Nobel Laureate from Nobelprize.org
Red Gold: the epic storyof blood from Public Broadcasting Service (PBS)
