Chapter 19: Blood We have mentioned the cardiovascular system the heart ( cardio ) and blood vessels ( vascular ) in several previous chapters. Most recently, in Chapter 18 (The Endocrine System), we saw that blood played the role of transporting endocrine hormones. Chapters 19 through 21 cover the cardiovascular system in detail. Chapter 19 covers blood, Chapter 20 covers the heart, and Chapter 21 covers the blood vessels and circulation. 19.0: Outline 19.1: Review/overview of the composition of blood Blood includes red blood cells (which transport oxygen); white blood cells (which provide immunity); platelets (which cause blood to clot); proteins like albumins, globulins, and fibrinogen; and other substances dissolved in water. 19.2: Red blood cells and oxygen transport The main job of red blood cells, or erythrocytes, is to transport oxygen (O 2) through the body. Within red blood cells, oxygen is carried by a protein named hemoglobin. Binding of O 2 to hemoglobin is temporary and reversible. At the lungs, where O 2 is abundant, hemoglobin gets loaded up with O 2. At other tissues of the body, where O 2 is more scarce, O 2 detaches from the hemoglobin and diffuses into the tissues. 19.3: White blood cells and antibodies The many functions of white blood cells include triggering the inflammatory response, phagocytosing invaders and cellular debris, and producing antibodies. Antibodies are proteins that bind antigens. The classification of blood types as A, B, AB, and O reflects the production of antibodies that bind to glycoprotein antigens on the surface of red blood cells. 19.4: Platelets and blood clotting Human platelets are fragments of large bone marrow cells called megakaryocytes. Stoppage of bleeding includes three phases: a vascular phase, in which damaged blood vessels are pinched off by their smooth muscles and become sticky; a platelet phase, in which platelets sticking to the endothelial cells release clotting factors and other materials; and a coagulation phase, in which clotting factors are sequentially activated in a cascade that creates a strong meshwork of the protein fibrin. 19.5: Recommended review questions 1
19.1: Review/overview of the composition of blood In this chapter we will expand our knowledge of blood, which we started learning about in Chapter 4. Recall from that chapter that blood is a connective tissue that (along with lymph) belongs to the subcategory of fluid connective tissue, and whose primary function is transport of materials around the body. In Chapter 4, we used 10 th Martini Figure 4-12 as a brief summary of the functions of blood cells: red blood cells (erythrocytes) transport oxygen; white blood cells (leukocytes) constitute a large part of the immune system, which protects the body from foreign intruders; and platelets enable blood clotting. (Technically, platelets are only fragments of cells, so red blood cells, white blood cells, and platelets are collectively called formed elements rather than cells.) To these fundamental functions of blood we can add (A) transport of many additional materials besides oxygen (hormones, nutrients, ions, etc.), (B) adjustment of the composition of interstitial fluids (which exchange substances with the blood), and (C) regulation of body temperature (via adjustment of flow to the surface of the body, where heat can be lost). Many details about the development of red blood cells, white blood cells, and platelets are now known, and are pictured in 10 th Martini Figure 19-10 (The Origins and Differentiation of Formed Elements). The big picture is that all of these arise from hematopoietic stem cells in the red bone marrow as opposed to the yellow bone marrow, which is fat. The clinical case highlighted in Chapter 19 is a case of aplastic anemia, in which red marrow has been replaced by yellow marrow. As a result, counts of red blood cells, white blood cells, and platelets are all reduced, and all of the corresponding functions (oxygen transport, fighting infections, and blood clotting, respectively) are impaired. Blood cells and platelets make up about 45% of blood; the remaining 55% or so is called plasma. Plasma consists of water, plasma proteins, and other solutes such as ions, nutrients, hormones, and wastes. Details are provided by 10 th Martini Figure 19-1 (The Composition of Whole Blood). The most abundant plasma proteins include the following: Albumins. Because they are the most abundant plasma proteins, they contribute more to the plasma s osmotic pressure (tendency to draw water via osmosis) than any other proteins. Globulins. These include antibodies (also called immunoglobulins), which bind to foreign invaders and proteins. Fibrinogen. This protein, when activated into fibrin, forms a meshwork that enables blood to clot. (See CTM section 19.4 below.) In the following sections, we will say a bit more about red blood cells, white blood cells, and platelets in turn. 19.2: Red blood cells and oxygen transport The development of red blood cells is shown in 10 th Martini Figure 19-10 (The Origins and Differentiation of Formed Elements) and also in Figure 19-5 (Stages of RBC Maturation). The 2
main thing to note is that red blood cells lose their nucleus! This allows them to fill most of their cellular space with hemoglobin, the oxygen-binding protein. Since mature red blood cells do not have DNA or transcription/translation machinery, they have limited ability to repair themselves. Because of this, an average red blood cell only lasts 120 days before it ruptures and its components are recycled. Hemoglobin is a protein with four polypeptide subunits (two alpha chains and two beta chains), each of which is associated with a flat heme group. Each heme group includes an iron (Fe) ion at its center, where O2 molecules covalently bind. Since each hemoglobin molecule contains four Fe ions, and since each Fe can bind one molecule of O2, each hemoglobin can bind up to four molecules of O2. 10 th Martini Figure 19-3 (The Structure of Hemoglobin) shows you the overall structure of hemoglobin and zooms in on the structure of the heme, but doesn t actually show O2! Don t lose sight of the fact that hemoglobin exists mostly to carry O2! A key aspect of O2 binding to hemoglobin is that it is reversible. This means that a given O2 molecule does not stay stuck on hemoglobin, but rather it hops on and off. Whether most of the hemoglobin binding sites are occupied or empty depends on the concentration of O2. In the pulmonary capillaries of the lungs, O2 is abundant, so hemoglobin picks up lots of O2 and its binding sites become almost 100% occupied. In the muscles and other working tissues of the body, O2 is constantly being used by the mitochondria as soon as it is delivered, so the O2 concentration is lower there and the O2 hops off the hemoglobin as it arrives. It then diffuses out of the blood into the surrounding tissues where it is used. Because oxygen is so vital for mitochondrial ATP production, and because hemoglobin is so vital for oxygen transport, hemoglobin problems cause a variety of clinical disorders. Anemia is the general term for an inadequate supply of red blood cells in the blood. Hematocrit the percentage of blood that is red blood cells only, excluding white blood cells, platelets and plasma is typically around 40-45% in healthy people, but can be much lower in anemic patients. 19.3: White blood cells and antibodies When we examined inflammation in Chapter 5, we saw that some cells released chemicals like histamine to trigger the inflammatory response, while other cells engulfed invading microbes and debris, a process called phagocytosis. All of these cells are white blood cells; thus the functions of white blood cells include stimulating the response to inflammation and phagocytosis. At this point we will add one additional function (out of many) of some white blood cells, which is to secrete Y-shaped proteins called antibodies (CTM Figure 19.1). Antibodies are produced by specific white blood cells called B lymphocytes, or B cells. They help defend the body by binding to antigens. An antigen is defined as anything to which an antibody will bind; in the context of the immune system, an antigen generally represents a piece of a foreign invader, such as a protein on the surface of a bacterium. By binding to antigens, antibodies facilitate the destruction or removal of the invader. 3
Each antibody binds to a very specific antigen, so each individual antibody is not much of a defense against anything. However, healthy people have a great variety of antibodies (thanks to cellular gene-splicing tricks that we won t go into here) which collectively can counter almost any antigen. CTM Figure 19.1: The molecular structure of an antibody. The tips of the arms of the Y are the parts that bind to an antigen. Image from wikimedia.org. As one specific example of how antibodies work, let s consider the ABO system of blood typing, which refers to antigens on the surface of red blood cells. In particular, these antigens are sugar groups attached to cell-surface proteins. CTM Figure 19.2 shows that everyone s blood cells have proteins with a core set of sugar groups, but some proteins have additional sugar groups that are recognized by antibodies as A antigens or B antigens. Each person s immune system is trained to distinguish self from non-self so that it does not make antibodies against the person s own proteins. A person whose red blood cells include only the A antigen will not make antibodies to the A antigen, but will make antibodies to the B antigen, which is foreign to this person. Conversely, someone whose red blood cells have only the B antigen will make anti-a antibodies but not anti-b antibodies. People with blood type AB have both A antigens and B antigens on their red blood cells, so they won t make antibodies to either A or B. Neither A antigens nor B antigens are naturally present in people with blood type O, so these people make antibodies to both A and B antigens. How is this relevant to human health? When these circulating antibodies encounter these cellsurface antigens, they cause the cells to clump together, as shown in 10 th Martini Figure 19-6b. This is a first step toward destruction of the foreign cells. This is why blood transfusions need to 4
be done between people with compatible blood types; if the types are NOT compatible, the recipient s immune system will simply destroy the transfused blood cells! CTM Figure 19.2: A, B, AB, and O blood types. The different colored hexagons on the proteins represent related but distinct sugars. Figure taken from Scott Freeman et al., Biological Science (5 th edition), 2014. Since type O blood doesn t have either A antigens or B antigens, people with type O blood can donate blood to anyone without provoking the recipients immune systems. Thus, people with type O blood are referred to as universal donors. Conversely, type AB blood doesn t include anti-a or anti-b antibodies, so people with type AB blood can receive blood from all blood types; these people are universal recipients. 19.4: Platelets and blood clotting Platelets cause blood to clot, thus preventing unnecessary loss of fluids and maintaining blood pressure. As shown in 10 th Martini Figure 19-10 (The Origins and Differentiation of Formed Elements), platelets form from megakaryocytes ( mega denotes the large size of these cells). Platelets in most vertebrates are legitimate full cells called thrombocytes (blood clotting is also called thrombosis); in humans and other mammals, though, platelets are cell fragments without nuclei. The process by which bleeding is stopped is called hemostasis ( hemo = blood, stasis = constant or steady). It can be conveniently divided into the three phases shown in 10 th Martini Figure 19-11 (The Vascular, Platelet, and Coagulation Phases of Hemostasis and Clot 5
Retraction). In the vascular phase, the damaged blood vessel stimulates its surrounding smooth muscle to contract, thus reducing blood flow through this now-leaky vessel. The membranes of the endothelial cells also become sticky, so these cells stick to each other and to platelets. In the platelet phase, platelets release many substances, including a bunch of proteins that ultimately cause clotting. These proteins are activated in the coagulation phase, diagrammed in step 3 of 10 th Martini Figure 19-11 and perhaps more clearly in CTM Figure 19.3. Each protein shown is a proenzyme, an inactive form of an enzyme which can be activated by cleavage (removal of a piece of the protein by another enzyme). In this cascade, an enzyme called kallikrein activates factor XII (remember your Roman numerals from the cranial nerves?); the activated factor XII (the subscript a stands for activated ) activates factor XI; the activated factor XI activates factor IX; and so on. The cascade ends with the conversion of the soluble protein fibrinogen into an insoluble form called fibrin. Fibrin is NOT an enzyme, but rather a rod-shaped protein whose units are cross-linked together by activated factor XIII. The resulting meshwork prevents the blood from spreading. Clotting is eventually stopped via the release of several anti-clotting substances, including heparin, which is commonly used clinically to prevent collected blood samples from clotting. CTM Figure 19.3: The blood clotting pathway. Each proenzyme, once activated, catalyzes a cleavage of the next proenzyme into its active form. Figure taken from blogs.scientificamerican.com/ the-curious-wavefunction/. 6
19.5: Recommended review questions If your understanding of this chapter is good, you should be able to answer the following 10 th Martini questions at the end of Chapter 19: review questions #6, 7, 11, 12, and 16, plus clinical case wrap-up questions #1 and 2. (Note that these are NOT the Checkpoint questions sprinkled throughout the chapter.) Explanation This document is my distillation of a chapter of the textbook Fundamentals of Anatomy & Physiology, Tenth Edition, by Frederic H. Martini et al. (a.k.a. the 10 th Martini ). While this textbook is a valuable resource, I believe that it is too dense to be read successfully by many undergraduate students. I offer Crowther s Tenth Martini so that students who have purchased the textbook may benefit more fully from it. No copyright infringement is intended. -- Greg Crowther 7