An Overview of Blood

• The cellular elements referred to as the formed elements include red blood cells (RBCs), white blood cells (WBCs), and cell fragments called platelets.

• The extracellular matrix, called plasma, makes blood unique among connective tissues because it is fluid.

Composition of Blood

• One such test, called a hematocrit, measures the percentage of RBCs, clinically known as erythrocytes, in a blood sample.

• The buffy coat because of its color; it normally constitutes less than 1 percent of a blood sample.

• The volume of erythrocytes after centrifugation is also commonly referred to as packed cell volume (PCV).

Characteristics of Blood

• Blood is viscous and somewhat sticky to the touch. It has a viscosity approximately five times greater than water.

• Viscosity is a measure of a fluid’s thickness or resistance to flow, and is influenced by the presence of the plasma proteins and formed elements within the blood.

• The viscosity of blood has a dramatic impact on blood pressure and flow.

• Consider the difference in flow between water and honey.

• The more viscous honey would demonstrate a greater resistance to flow than the less viscous water. The same principle applies to blood.

Blood Plasma

• Blood plasma is the liquid component of blood that carries red and white blood cells, platelets, and other substances throughout the body.

• It is composed of water, proteins, and other substances.

Plasma Proteins

• Albumin is the most abundant of the plasma proteins.

• The second most common plasma proteins are the globulins.

• The least abundant plasma protein is fibrinogen.

Production of the Formed Elements

• This restricts the frequency with which donors can contribute their blood.

• The process by which this replacement occurs is called hemopoiesis, or hematopoiesis (from the Greek root haima- = “blood”; -poiesis = “production”).

Sites of Hemopoiesis

• Sites of hemopoiesis are the places in the body where blood cells are produced.

  • This includes the bone marrow, the spleen, and the liver.

Differentiation of Formed Elements from Stem Cells

• The totipotent stem cell is the zygote, or fertilized egg.

• The next level is the pluripotent stem cell, which gives rise to multiple types of cells of the body and some of the supporting fetal membranes.

• One step lower on the hierarchy of stem cells is the hemopoietic stem cell, or hemocytoblast.

• Hemopoiesis begins when the hemopoietic stem cell is exposed to appropriate chemical stimuli collectively called hemopoietic growth factors, which prompt it to divide and differentiate.

• Lymphoid stem cells give rise to a class of leukocytes known as lymphocytes, which include the various T cells, B cells, and natural killer (NK) cells, all of which function in immunity.

• Myeloid stem cells give rise to all the other formed elements, including the erythrocytes; megakaryocytes that produce platelets; and a myeloblast lineage that gives rise to monocytes and three forms of granular leukocytes: neutrophils, eosinophils, and basophils.

Hemopoietic Growth Factors

• Erythropoietin (EPO) is a glycoprotein hormone secreted by the interstitial fibroblast cells of the kidneys in response to low oxygen levels.

• Thrombopoietin, another glycoprotein hormone, is produced by the liver and kidneys. It triggers the development of megakaryocytes into platelets.

• Cytokines are glycoproteins secreted by a wide variety of cells, including red bone marrow, leukocytes, macrophages, fibroblasts, and endothelial cells.

• Colony-stimulating factors (CSFs) are glycoproteins that act locally, as autocrine or paracrine factors.

• Interleukins are another class of cytokine signaling molecules important in hemopoiesis.

Bone Marrow Sampling and Transplants

• Sometimes, a healthcare provider will order a bone marrow biopsy, a diagnostic test of a sample of red bone marrow, or a bone marrow transplant, a treatment in which a donor’s healthy bone marrow—and its stem cells—replaces the faulty bone marrow of a patient.

Erythrocytes

• The erythrocyte, commonly known as a red blood cell (or RBC), is by far the most common formed element:

• A single drop of blood contains millions of erythrocytes and just thousands of leukocytes.

Shape and Structure of Erythrocytes

• Erythrocytes, or red blood cells, are biconcave discs that are about 7.5 micrometers in diameter.

• They have a thin, flexible cell membrane that encloses a small amount of cytoplasm and a single nucleus.

• The nucleus is usually absent in mature erythrocytes, and the cytoplasm contains hemoglobin, which is responsible for carrying oxygen throughout the body.

Hemoglobin

• Hemoglobin is a large molecule made up of proteins and iron. It consists of four folded chains of a protein called globin, designated alpha 1 and 2, and beta 1 and 2.

• Each of these globin molecules is bound to a red pigment molecule called heme, which contains an ion of iron (Fe2+).

• In the lungs, hemoglobin picks up oxygen, which binds to the iron ions, forming oxyhemoglobin.

• About 23–24 percent of it binds to the amino acids in hemoglobin, forming a molecule known as carbaminohemoglobin.

• Lower percentages reflect hypoxemia, or low blood oxygen. The term hypoxia is more generic and simply refers to low oxygen levels.

Lifecycle of Erythrocytes

• Iron - We have said that each heme group in a hemoglobin molecule contains an ion of the trace mineral iron.

• Copper - A trace mineral, copper is a component of two plasma proteins, hephaestin and ceruloplasmin.

• Zinc - The trace mineral zinc functions as a co-enzyme that facilitates the synthesis of the heme portion of hemoglobin.

• B vitamins - The B vitamins folate and vitamin B12 function as co-enzymes that facilitate DNA synthesis.

Disorders of Erythrocytes

• The size, shape, and number of erythrocytes, and the number of hemoglobin molecules can have a major impact on a person’s health.

• When the number of RBCs or hemoglobin is deficient, the general condition is called anemia.

• A characteristic change in the shape of erythrocytes is seen in sickle cell disease (also referred to as sickle cell anemia).

• Vitamin-deficient anemias generally involve insufficient vitamin B12 and folate.

• Thalassemia is an inherited condition typically occurring in individuals from the Middle East, the Mediterranean, African, and Southeast Asia, in which maturation of the RBCs does not proceed normally.

• An elevated RBC count is called polycythemia and is detected in a patient’s elevated hematocrit.

Leukocytes and Platelets

• The leukocyte, commonly known as a white blood cell (or WBC), is a major component of the body’s defenses against disease.

• Leukocytes protect the body against invading microorganisms and body cells with mutated DNA, and they clean up debris.

• Platelets are essential for the repair of blood vessels when damage to them has occurred; they also provide growth factors for healing and repair.

Characteristics of Leukocytes

• Leukocytes are white blood cells that are part of the immune system.

• They are produced in the bone marrow and are responsible for defending the body against infection and disease.

• Leukocytes are typically larger than other types of blood cells and have a nucleus.

• They can be divided into two main categories: granulocytes and agranulocytes.

• Granulocytes are further divided into neutrophils, eosinophils, and basophils.

• Agranulocytes are further divided into lymphocytes and monocytes. Leukocytes are able to move around the body and can recognize and destroy foreign substances.

Classification of Leukocytes

• Granular leukocytes contain abundant granules within the cytoplasm.

• While granules are not totally lacking in agranular leukocytes, they are far fewer and less obvious.

• Agranular leukocytes include monocytes, which mature into macrophages that are phagocytic, and lymphocytes, which arise from the lymphoid stem cell line.

Disorders of Leukocytes

• Leukopenia is a condition in which too few leukocytes are produced.

• Leukemia is a cancer involving an abundance of leukocytes.

• Lymphoma is a form of cancer in which masses of malignant T and/or B lymphocytes collect in lymph nodes, the spleen, the liver, and other tissues.

Platelets

• A platelet is not a cell but rather a fragment of the cytoplasm of a cell called a megakaryocyte that is surrounded by a plasma membrane.

Disorders of Platelets

• Thrombocytosis is a condition in which there are too many platelets.

• This may trigger formation of unwanted blood clots (thrombosis), a potentially fatal disorder.

• If there is an insufficient number of platelets, called thrombocytopenia, blood may not clot properly, and excessive bleeding may result.

Hemostasis

• Platelets are key players in hemostasis, the process by which the body seals a ruptured blood vessel and prevents further loss of blood.

• Failure of any of these steps will result in hemorrhage excessive bleeding.

Vascular Spasm

• In vascular spasm, the smooth muscle in the walls of the vessel contracts dramatically.

• This smooth muscle has both circular layers; larger vessels also have longitudinal layers.

Coagulation

• Those more sophisticated and more durable repairs are collectively called coagulation, the formation of a blood clot.

• The result is the production of a gelatinous but robust clot made up of a mesh of fibrin, an insoluble filamentous protein derived from fibrinogen, the plasma protein introduced earlier in which platelets and blood cells are trapped.

Clotting Factors Involved in Coagulation

• In the coagulation cascade, chemicals called clotting factors (or coagulation factors) prompt reactions that activate still more coagulation factors.

• The extrinsic pathway, which normally is triggered by trauma.

• The intrinsic pathway, which begins in the bloodstream and is triggered by internal damage to the wall of the vessel.

• Extrinsic Pathway: The quicker responding and more direct extrinsic pathway (also known as the tissue factor pathway) begins when damage occurs to the surrounding tissues, such as in a traumatic injury.

• Intrinsic Pathway: The intrinsic pathway (also known as the contact activation pathway) is longer and more complex.

Common Pathway

• Both the intrinsic and extrinsic pathways lead to the common pathway, in which fibrin is produced to seal off the vessel.

• Once factor X has been activated by either the intrinsic or extrinsic pathway, the enzyme prothrombinase converts factor II, the inactive enzyme prothrombin, into the active enzyme thrombin.

Fibrinolysis

• Fibrinolysis is the gradual degradation of the clot.

• During this process, the inactive protein plasminogen is converted into the active plasmin, which gradually breaks down the fibrin of the clot.

Plasma Anticoagulants

• An anticoagulant is any substance that opposes coagulation.

• Antithrombin inactivates factor X and opposes the conversion of prothrombin (factor II) to thrombin in the common pathway.

• Blood Typing: Blood transfusions in humans were risky procedures until the discovery of the major human blood groups by Karl Landsteiner, an Austrian biologist and physician, in 1900.

Antigens, Antibodies, and Transfusion Reactions

• Antigens are substances that the body does not recognize as belonging to the “self” and that therefore trigger a defensive response from the leukocytes of the immune system.

• Because the arms of the Y-shaped antibodies attach randomly to more than one nonself erythrocyte surface, they form clumps of erythrocytes. This process is called agglutination.

• As the erythrocyte clumps are degraded, in a process called hemolysis, their hemoglobin is released into the bloodstream.

• The ABO Blood Group: Although the ABO blood group name consists of three letters, ABO blood typing designates the presence or absence of just two antigens, A and B. Both are glycoproteins.

Rh Blood Groups

• The Rh blood group is classified according to the presence or absence of a second erythrocyte antigen identified as Rh. (It was first discovered in a type of primate known as a rhesus macaque, which is often used in research, because its blood is similar to that of humans.)

• Hemolytic disease of the newborn (HDN) or erythroblastosis fetalis, may cause anemia in mild cases, but the agglutination and hemolysis can be so severe that without treatment the fetus may die in the womb or shortly after birth.