Chapter 11: Blood Notes

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Hemostasis (cont.) •Disorders of Coagulation (Coagulopathies) - hemophilia - von Willebrand disease (vWD) - disseminated intravascular coagulation (DIC)

*Hemophilia in its classical form (hemophilia A) is a disease males inherit from their mothers and is due to a deficiency of a coagulation factor, called factor VIII. The disorder causes painful bleeding into skin, joints, and muscles. Concentrated factor VIII is given intravenously to reduce the symptoms. *Von Willebrand disease (vWD ) is a deficiency of a specific protein of the factor VIII complex that is different from the part involved in hemophilia. *Disseminated intravascular coagulation (DIC) occurs when the clotting mechanism is activated simultaneously throughout the cardiovascular system. The trigger is usually a severe bacterial infection. Small clots form and obstruct blood flow into tissues and organs, particularly the kidney, leading to renal failure. As the clotting mechanisms are overwhelmed, severe bleeding occurs

Word Analysis and Definition •Identify the prefix, root, and suffix of the following term. Then define it: - agglutinate prefix- ag root- glutin suffix- ate

- agglutinate prefix- ag- to root- glutin- stick together, glue suffix- ate- composed of, pertaining to

Word Analysis and Definition •Identify the prefix, root, and suffix of the following term. Then define it: - hypoxic prefix- hypo root- ox suffix- ic

- hypoxic prefix- hypo-deficient root- ox- oxygen suffix- ic-pertaining to

Laboratory Tests to Evaluate Blood Coagulation •Platelet Count •Prothrombin Time (PT) •Activated Partial Thromboplastin Time (aPTT)

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Components of Blood •Functions of Blood - maintain homeostasis - maintain body temperature - transport nutrients, vitamins, and minerals

1. Maintain the body's homeostasis. 2. Maintain body temperature. Warm blood is transported from the interior of the body to its surface, where heat is released from the blood. 3. Transport nutrients, vitamins, and minerals from digestive system and storage areas to organs and cells where they are needed. Examples of nutrients are glucose and amino acids. 4. Transport waste products from cells and organs to the liver and kidneys for detoxification and excretion. Examples are creatinine , urea , bilirubin, and lactic acid. 5. Transport hormones from endocrine glands to the target cells. Examples are insulin and thyroxin. 6. Transport gases to and from the lungs and cells. Examples are oxygen and carbon dioxide. 7. Protect against foreign substances . Cells and chemicals in the blood are an important part of the immune system for dealing with microorganisms and toxins. 8. Form clots . Clots provide protection against blood loss and are the first step in tissue repair and restoration of normal function. 9. Regulate pH and osmosis .

White Blood Cells (Leukocytes) •Types of White Blood Cells - agranulocytes 1. monocytes a. structure b. function

1. Monocytes are the largest blood cell and are normally 3% to 8% of the total WBC count. Monocytes leave the bloodstream and become macrophages that phagocytize bacteria, dead neutrophils, and dead cells in the tissues.

Red Blood Cells (Erythrocytes) •Structure and Function of Red Blood Cells - function of red blood cells 1. transport oxygen 2. transport carbon dioxide 3. transport nitric oxide

1. Transport oxygen (O 2 ) from the lungs to cells all over the body. Oxygen is transported in combination with hemoglobin ( oxyhemoglobin ). 2. Transport carbon dioxide (CO 2 ) from the tissue cells to the lungs for excretion. 3. Transport nitric oxide (NO), a gas produced by cells lining the blood vessels that signals smooth muscle to relax and is also a transmitter of signals between nerve cells.

Hemostasis (cont.) •Hemostasis - vascular spasm - platelet plug - blood coagulation

1. Vascular spasm —an immediate but temporary constriction of the injured blood vessel. 2. Platelet plug formation —an accumulation of platelets that bind themselves together and adhere to surrounding tissues. The binding and adhesion of platelets is mediated through von Willebrand factor ( vWF), a protein produced by the cellslining blood vessels. 3. Blood coagulation —the process beginning with the production of molecules that make prothrombin and thrombin and finishing with the formation of a blood clot that traps blood cells, platelets, and tissue fluid in a network of fibrin

White Blood Cells (Leukocytes) •Types of White Blood Cells - agranulocytes 2. lymphocytes

2. Lymphocytes are normally 25% to 35% of the total WBC count. They are the smallest type of WBC. Lymphocytes are produced in red bone marrow and migrate through the bloodstream to lymphatic tissues—lymph nodes, tonsils, spleen, and thymus—where they proliferate. There are two main types of lymphocyte: a. B cells that differentiate into plasma cells. These are stimulated by bacteria or toxins to produce antibodies , or immunoglobulins (Igs). b. T cells that attach directly to foreign antigen-bearing cells such as bacteria, which they kill with toxins they secrete.

Components of Blood (cont.) •Functions of Blood - transport waste products - transport hormones - transport gases

4. Transport waste products from cells and organs to the liver and kidneys for detoxification and excretion. Examples are creatinine , urea , bilirubin, and lactic acid. 5. Transport hormones from endocrine glands to the target cells. Examples are insulin and thyroxin. 6. Transport gases to and from the lungs and cells. Examples are oxygen and carbon dioxide.

Components of Blood (cont.) •Functions of Blood - protect against foreign substances - form clots - regulate pH and osmosis

7. Protect against foreign substances . Cells and chemicals in the blood are an important part of the immune system for dealing with microorganisms and toxins. 8. Form clots . Clots provide protection against blood loss and are the first step in tissue repair and restoration of normal function. 9. Regulate pH and osmosis .

Blood Groups and Transfusions •Red Cell Antigens - ABO blood group

ABO Blood Group The two major antigens on the cell surface are antigen A and antigen B. A person with only antigen A has type A blood. A person with only antigen B has type B blood. A person with both antigen A and antigen B has type AB blood and is a universal recipient who can receive blood from any other type in the ABO system. A person with neither antigen has type O blood and is a universal donor able to give blood to any other person no matter what that person's blood type is.

Abbreviations •Define the following abbreviations: - CO2 - Hb - NO - O2

CO2-carbon dioxide Hb-hemoglobin NO-nitric oxide O2-oxygen

Components of Blood •Components of Blood

Components of Blood Blood is a type of connective tissue and consists of cells contained in a liquid matrix. Blood volume varies with body size and the amount of adipose tissue. An average-size adult has about 5 L (liters) (10 pints) of blood that represents some 8% of body weight. If a specimen of blood is collected in a tube and centrifuged, the cells of the blood are packed into the bottom of the tube.

White Blood Cells (Leukocytes) (cont.) •Types of White Blood Cells - eosinophils

Eosinophils are normally 2% to 4% of the total WBC count. They are mobile cells that leave the bloodstream to enter tissue undergoing an allergic response. In allergic reactions, the number and percentage of eosinophils increase.

White Blood Cells (Leukocytes) •Types of White Blood Cells - granulocytes - neutrophils

Granulocytes Neutrophils are normally 50% to 70% of the total WBC count. They are also called polymorphonuclear leukocytes (PMNLs). These cells phagocytize bacteria, fungi, and some viruses and secrete a group of enzymes called lysozymes, which destroy some bacteria. In bacterial infections, the number and percentage of neutrophils increase dramatically. In neutropenia , the number of neutrophils is diminished below normal.

Blood Groups and Transfusions •Red Cell Antigens - antigens - antibodies - agglutination 1. ABO and Rh blood groups

On the surfaces of red blood cells are molecules called antigens. In the plasma, antibodies are present. Each antibody can combine with only a specific antigen. If the plasma antibodies combine with a red cell antigen, bridges are formed that connect the red cells together. This is called agglutination , or clumping, of the cells. Hemolysis (rupture) of the cells also occurs. The antigens on the surfaces of the cells have been categorized into groups, of which two are the most important. These are the ABO and Rhesus (Rh) blood groups

Hemostasis •Hemostasis: the control of bleeding - platelets 1. coagulation factors 2. vasoconstrictors 3. chemicals

Platelets (also called thrombocytes) play a key role in hemostasis. They are minute fragments of large bone marrow cells called megakaryocytes . They have no nucleus. Platelet granules secrete chemicals that are critical to hemostasis: • Coagulation factors —proteins and enzymes—that initiate the process. • Vasoconstrictors that cause constriction in injured blood vessels. • Chemicals that attract neutrophils and monocytes to sites of inflammation.

Word Analysis and Definition •Define the difference in the following terms which share the same suffix: - agranulocyte - granulocyte - leukocyte - lymphocyte - monocyte

agranulocyte-a white blood cell without any granules in its cytoplasm granulocyte-a white blood cell that contains multiple small granules in its cytoplasm leukocyte-white blood cells lymphocyte-small white blood cell with a large nucleus monocyte-largest blood cell

Word Analysis and Definition •Give the correct term for the following definitions: - decreased number of RBCs - a breakdown product of skeletal muscle

anemia- decreased number of RBCs creatinine-a breakdown product of skeletal muscle

Word Analysis and Definition •Identify the correct term from the given definitions: - a substance that prevents clots - a clot attached to a diseased blood vessel or heart lining - the process of blood clotting

anticoagulant-a substance that prevents clots thrombus-a clot attached to a diseased blood vessel or heart lining coagulation- the process of blood clotting

Word Analysis and Definition •Define the following root elements: - coll - ferrit - chrom - cyt - corpus

coll-glue ferrit-iron chrom-color cyt-cell corpus-body

Abbreviations •Define the following abbreviations: - dL - fL - L - MCH - MCHC

dL-deciliter fL-femtorliter L-liter MCH-mean corpuscular hemoglobin MCHC-mean corpuscular hemoglobin concentration

Word Analysis and Definition •Identify the prefix, root, and suffix of the following word. Define the term. - disseminate prefix - dis root - semin suffix - ate

disseminate prefix - dis-apart root - semin-scatter seed suffix - ate-composed of, pertaining to

Word Analysis and Definition •How do the terms heterophile and Monospot test relate to one another? - heterophile - Monospot

heterophile-pertaining to antibodies present during a disease but not directed against the causative agent Monospot test- detects hetarophille antibodies infectious mononcleosis

Word Analysis and Definition •Identify the prefix, root, and suffix of the following word. Define the term. - recombinant prefix - re root - combin suffix - ant

recombinant prefix - re-again root - combin-combine suffix - ant-forming

Word Analysis and Definition •Give the correct term for the following definitions: - insoluble material that settles to the bottom of a liquid - end-product of nitrogen metabolism

sediment- insoluble material that settles to the bottom of a liquid urea-end-product of nitrogen metabolism

Components of Blood •Formed Elements - RBCs - hematocrit - WBCs - platelets - plasma - serum

These cells are called the formed elements of blood and consist of 99% red blood cells ( RBCs), together with white blood cells ( WBCs) and platelets. The blood sample is normally about 45% formed elements. The hematocrit (Hct) is the percentage of total blood volume composed of red blood cells. The red blood cells can account for 40% to 54% of the total blood volume in normal males and 38% to 47% in females. Plasma is the remaining 55% of the blood sample. It is a clear, yellowish liquid that is 91% water. Plasma is the fluid noncellular part of blood. Plasma is a colloid , a liquid that contains suspended particles, most of which are the plasma proteins named: • Albumin —makes up 58% of the proteins. • Globulin —makes up 38% of the plasma proteins. Antibodies are globulins. • Fibrinogen —makes up 4% of the plasma proteins and is part of the mechanism for blood clotting. Nutrients, waste products, hormones, and enzymes are dissolved in plasma for transportation. When blood is allowed to clot and the solid clot is removed, serum is left. Serum is identical to plasma except for the absence of clotting proteins.

Hemostasis (cont.) •Disorders of Coagulation (Coagulopathies) - thrombocytopenia - thrombotic thrombocytopenic purpura (TTP) - hemolytic uremic syndrome (HUS) - Henoch-Schonlein purpura

Thrombocytopenia is a low platelet count (below a 100,000/mm 3 of blood). It occurs when bone marrow is destroyed by radiation, chemotherapy, or leukemia. Small capillary hemorrhages called petechiae and bruises can be seen in the skin. Idiopathic (immunologic) thrombocytopenic purpura (ITP) is an acute self-limiting form of the disease usually seen in children. Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) are acute, potentially fatal disorders in which loose strands of fibrin are deposited in numerous small blood vessels. This causes damage to platelets and RBCs, causing thrombocytopenia and hemolytic anemia. Henoch-Schönlein purpura (anaphylactoid purpura) is a disorder involving purpura, joint pain, and glomerulonephritis. The etiology is unknown. Most cases resolve spontaneously.

Hemostasis (cont.) •Disorders of Coagulation (Coagulopathies) - thrombus - embolus

Thrombus formation ( thrombosis ) is a clot that attaches to diseased or damaged areas on the walls of blood vessels or the heart. If part of the thrombus breaks loose and moves through the circulation, it is called an embolus .

Abbreviations •Define the following abbreviations: - MCV - ug - pg - TIBC

MCV-mean corpuscular volume ug-microgram pg-picogram TIBC-total iron blinding capacity

White Blood Cells (Leukocytes) (cont.) •Disorders of White Blood Cells - leukocytosis - leukemia

*Leukocytosis is defined as a total WBC count of normal cells exceeding 10,000/mm 3 . When the majority of the increased cells are neutrophils (polymorphonuclear leukocytes), an acute infection is usually present, for example, appendicitis or bacterial pneumonia. Allergic reactions increase the number of eosinophils. Typhoid fever, malaria, and tuberculosis increase the number of monocytes. Whooping cough and infectious mononucleosis increase the number of lymphocytes. *Leukemia is cancer of the hematopoietic tissues and produces a high number of leukocytes and their precursors in the WBC count. As the leukemic cells proliferate, they take over the bone marrow and cause a deficiency of normal RBCs, WBCs, and platelets . This makes the patient anemic and vulnerable to infection and bleeding. Myeloid leukemia is characterized by uncontrolled production of granulocytes and their precursors. It can be in an acute or chronic form. Lymphoid leukemia is characterized by uncontrolled production of lymphocytes. It can be in an acute or chronic form. Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and is curable with modern treatments, such as chemo therapy and bone marrow and umbilical cord stem cell transplants.

Red Blood Cells (Erythrocytes) (cont.) •Disorders of Red Blood Cells - anemia

Anemia is a reduction in the number of RBCs or in the amount of hemoglobin each RBC contains. Both of these conditions reduce the oxygen-carrying capacity of the blood and produce the symptoms of shortness of breath (SOB ) and fatigue. They also produce pallor (paleness of the skin) because of the deficiency of the red-colored oxyhemoglobin, the combination of oxygen and hemoglobin, and the red blood cells are hypochromic. There are several types of anemia: • Iron-deficiency anemia is the diagnosis for Mrs. Luisa Sosin. In her case, the cause was chronic bleeding from her gastrointestinal tract due to the aspirin and other painkillers she was taking. Her stools were positive for occult blood. Other causes can be heavy menstrual bleeding or a diet deficient in iron. • Pernicious anemia (PA) is due to vitamin B 12 deficiency. This is caused by a shortage of intrinsic factor, which is normally secreted by cells in the lining of the stomach and binds with vitamin B 12 ; this complex is absorbed into the bloodstream. Without vitamin B 12 , hemoglobin cannot be formed. The RBCs decrease in number and in hemoglobin concentration and increase in size ( macrocytic ). • Sickle cell anemia (also called sickle cell disease ) is a genetic disorder found most commonly in African Americans, Africans, and some Mediterranean populations. It results from the production of an abnormal hemoglobin that causes the RBCs to form a rigid sickle cell shape. The abnormal cells are sticky, clump together ( agglutinate ), and block small capillaries. This causes intense pain in the hypoxic tissues (a sickle cell crisis) and can cause stroke and kidney and heart failure. There is a minor form of the disease, sickle cell trait, in which symptoms rarely occur and do not progress to the full-blown disease. • Hemolytic anemia is due to excessive destruction of normal and abnormal RBCs. Hemolysis can be caused by such toxic substances as snake and spider venoms, mushroom toxins, and drug reactions. Trauma to RBCs by hemodialysis or heart-lung machines can produce a hemolytic anemia. • Aplastic anemia is a condition in which the bone marrow is unable to produce sufficient new cells of all types—red cells, white cells, and platelets. It can be associated with exposure to radiation, benzene, and certain drugs.

White Blood Cells (Leukocytes) (cont.) •Types of White Blood Cells -basophils

Basophils are normally less than 1% of the total WBC count. Basophils migrate to damaged tissues, where they release histamine (which increases blood flow) and heparin (which prevents blood clotting).

White Blood Cells (Leukocytes) (cont.) •Disorders of White Blood Cells - leukopenia - pancytopenia

Leukopenia results when the WBC count drops below 5000 cells/mm 3 of blood. Leuko penia is seen in viral infections such as measles, mumps, chickenpox, poliomyelitis, and AIDS. Pancytopenia occurs when the erythrocytes (RBCs), leukocytes (WBCs), and thrombocytes ( platelets ) in the circulating blood are all markedly reduced. This can occur with cancer chemotherapy.

Red Blood Cells (Erythrocytes) (cont.) •Structure and Function of Red Blood Cells - life history of red blood cells

Life History of Red Blood Cells Red blood cell formation ( erythropoiesis ) occurs in the spaces in bones filled with red bone marrow. Hematopoietic stem cells become nucleated erythroblasts and then nonnucleated erythrocytes, which are released into the bloodstream. A hormone, erythropoietin , produced by the kidneys and liver, controls the rate of RBC production. A lack of oxygen in the body's tissues triggers the release of erythropoietin, which travels in the blood to the red bone marrow to stimulate RBC production. RBC production is also influenced by the availability of iron, the B vitamins B 12 and folic acid, and amino acids through absorption from the digestive tract. The average life span of an RBC is 120 days, during which time the cell has circulated through the body about 75,000 times. With age, the cells become more fragile, and squeezing through tiny capillaries ruptures them. Macrophages in the liver and spleen take up the hemoglobin that is released and break it down into its components heme and globin. The heme is broken down into iron and into a rust-colored pigment called bilirubin.

Blood Groups and Transfusions •Red Cell Antigens - Rh Blood Group

Rhesus (Rh) Blood Group If an Rh antigen is present on an RBC surface, the blood is said to be Rh-positive (Rh ; ). If there is no Rh antigen on the surface, the blood is Rh-negative (Rh : ). The presence or absence of Rh antigen is inherited. If an Rh-negative person receives a transfusion of Rh-positive blood, anti-Rh antibodies will be produced. This can cause RBC agglutination and hemolysis. If an Rh-negative woman and an Rh-positive man conceive an Rh-positive child, the placenta normally prevents maternal and fetal blood from mixing. However, at birth or during a miscarriage, fetal cells can enter the mother's bloodstream. These Rh-positive cells stimulate the mother's tissues to produce Rh-antibodies. If the mother becomes pregnant with a second Rh-positive fetus, her Rh-antibodies can cross the placenta and agglutinate and hemolyze the fetal RBCs. This causes hemolytic disease of the newborn (HDN, or erythroblastosis fetalis). Hemolytic disease of the newborn due to Rh incompatibility can be prevented. The Rh-negative mother should be given Rh immune globulin (RhoGAM) during pregnancy, or soon after giving birth to an Rh-positive child . Other causes of hemolytic disease of the newborn include ABO incompatibility, incompatibility in other blood group systems, hereditary spherocytosis, and some infections acquired before birth.

Word Analysis and Definition •Explain the difference in the following terms which have the same root element: - erythroblast - erythropoiesis - erythropoietin

S/-blast germ cell R/CF-erythr/o-red S/-poiesis to make R/CF-erythr/o- red S/-poietin the maker R/CF-erythr/o- red

Red Blood Cells (Erythrocytes) •Structure and Function of Red Blood Cells - structure of red blood cells

Structure of Red Blood Cells The main component of RBCs is hemoglobin ( Hb ), which gives the cell its red color. Hemoglobin occupies about one-third of the total cell volume and is composed of the iron-containing pigment heme bound to a protein called globin . The rest of the red blood cell consists of the cell membrane, water, electrolytes, and enzymes. Mature RBCs do not have a nucleus. Each RBC is a biconcave disc with edges that are thicker than the center. This biconcave shape gives the disc a larger surface area than if it were a sphere. The biconcave surface area enables a more rapid flow of gases into and out of the RBC. RBCs are unable to move themselves and are dependent on the heart and blood vessels to move them around the body.

Pharmacology of Blood Clotting •Aspirin •Heparin •Hirudin •Warfarin •Streptokinase •Tissue Plasminogen Activator (tPA)

• Aspirin reduces platelet adherence and aggregation. It is used in 81-mg doses to reduce the incidence of heart attacks. • Heparin is a polysaccharide that prevents prothrombin and fibrin formation. It has to be given parenterally (not through the digestive tract), and recently a form of heparin that can be given subcutaneously has been approved. Its dose is monitored by activated partial thromboplastin time (aPTT). • Hirudin is a potent anticoagulant produced by recombinant DNA technology. It blocks thrombin formation. • Warfarin (Coumadin) inhibits the synthesis of prothrombin and other coagulation factors, so it acts as an anticoagulant. It is given by mouth, and its dose is monitored by prothrombin times (PTs), which are reported as an International Normalized Ratio (INR). • Dabigatran etexilate (Pradaxa) and rivaroxaban (Xarelto) inhibits the synthesis of thrombin and is given by mouth to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. • Streptokinase, derived from hemolytic streptococci, dissolves the fibrin in blood clots. Given intravenously within 3 to 4 hours of a heart attack, it is often effective in dissolving the clot that has caused the heart attack. • Tissue plasminogen activator (tPA) binds strongly to fibrin and dissolves clots that havecaused heart attacks. It is similar in effect and use to streptokinase. Reteplase and urokinase are forms of tPA.

Red Blood Cells (Erythrocytes) (cont.) •Disorders of Red Blood Cells - hemoglobinopathies - polycythemia vera

• Hemoglobinopathies , such as sickle cell disease and thalassemia , with their inherited abnormal hemoglobins, also cause hemolysis. Hemolysis can also occur through incompatible blood transfusions or maternalfetal incompatibilities. Jaundice is a complication. • Polycythemia vera is an overproduction of RBCs and WBCs due to an unknown cause.


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