Chapter 17 Blood Lecture Objectives

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Define diapedesis.

Diapedesis: It's the movement or passage of blood cells, especially white blood cells, through intact capillary walls into surrounding body tissue. Greek "Dia," "Pedan."

Describe the chemical make-up of hemoglobin.

Hemoglobin: It's a protein that makes red blood cells red, binds easily and reversible with oxygen, and most oxygen carried in blood is bound to hemoglobin. Chemical: it's made of a protein called globin bound to the red heme pigment. Globin: It consists of four polypeptide chains (two alpha, two beta) with each binding a heme group. Each heme group bears an atom of iron. A hemoglobin molecule can transport four molecules of oxygen because iron atom can combine reversibly with one molecule of oxygen. A single red blood cell contains about 250 million hemoglobin. When oxygen binds to iron, the hemoglobin (now called *oxyhemoglobin*), assumes a new three-dimensional shape and becomes red. In the tissues, the process is reversed. Oxygen detaches from iron, hemoglobin resumes its former shape, and the resulting *deoxyhemoglobin* becomes dark red.

Describe the composition of whole blood.

WHOLE BLOOD: It's plasma and formed elements. Plasma: It contains over 100 different dissolved solutes, including nutrients, gases, hormones, wastes and products of cell activity, ions and proteins. Plasma proteins are the most abundant plasma solutes. Except for hormones and gamma globulins, most plasma proteins are produced by the liver. Plasma proteins serve a variety of functions, but they are not taken up by cells to be used as fuels or metabolic nutrients as are most other plasma solutes, such as glucose, fatty acids, and amino acids. Formed Elements: The formed elements of blood are erythrocytes, leukocytes, and platelets. Formed Elements: 1. Erythrocytes: Red blood cells. 2. Leukocytes: White blood cells. They are only formed elements that are complete cells, with nuclei and the usual organelles. They are far less numerous than red blood cells. 3. Platelets:

Describe the ABO and Rh blood groups.

ABO: Groups that are based on the presence or absence of two agglutinogens, type A or B. It will be one of the following: A, B, AB, or O. The O blood group, which has neither, will be the most common ABO group. These will have the presence of *agglutinins.* These act against RBCs carrying ABO antigens that are not present on the own person's red blood cells. B = Anti A antibodies A = Anti B antibodies O = Anti A and Anti B antibodies AB: Universal recipient, can receive any blood B: Anti A, can receive B, O A: Anti B, can receive A, O O: Universal donor, Anti A, Anti B, can receive O Rh: There are 50 kinds of Rh agglutinogens, each of which is called an Rh factor. The C, D, and E are the most common. If an Rh- person receives Rh+ blood, the immune system will become sensitized and begins producing anti-Rh antibodies.But the second time, a typical transfusion reaction occurs in which the recipient's antibodies attack and rupture the donor RBCs.

Explain how the processes of retraction and fibrinolysis relate to the natural elimination of a blood clot.

Clot Retraction: The clot will be stabilized further by a platelet-induced processed called clot retraction. Platelets contain contractile proteins (actin and myosin), which contract similar to muscle cells. They contract to pull the fibrin strands, squeezing SERUM (plasma minus clotting proteins) from the mass, compacting the clot ad drawing the ruptured edges of the blood vessel more closely together. This deals with Platelet-derived growth factor (PDGF) released by platelet granulation stimulates smooth muscle cells and fibrinoblasts to divide and build the wall. Endothelial cells will then multiply and build the wall once more. Fibrinolysis: This process removes unneeded clots then healing has occurred. It's crucial because small clots are formed continually in vessels throughout the body. Without fibrinolysis, blood vessels would gradually become blocked. The critical natural "clot-buster" is a fibrin-digesting enzyme called PLASMIN. It's produced by the activation of plasminogen. These are incorporated into a forming clot, which remains inactive until proper signaling occurs. The clot will lead to tissue plasminogen activator (tPA), XIII, and thrombin serving as plasminogen activators. That process dissolves the clot.

Identify the hemostatic disorders.

Disorders of Hemostasis: There are two kinds. 1. Thromboembolic Disorders: These result from conditions that have undesirable clot disorders. A clot that develops and persists in an unbroken blood vessel is called a *thrombus*. It can become large and block circulation to cells beyond the occupation and lead to death of those tissues. These can break away and float freely within the bloodstream, which becomes a *embolus,* which can become an *embolism* and obstruct vessels. Ex: Cerebral embolism can lead to a stroke. Slowly forming blood can be another problem leading to these disorders. This leads to aspirin, heparin, and warfarin to reduce these disorders. Disseminated intravascular coagulation: Widespread clotting occurs within intact blood vessels and the residual blood becomes unable to clot. 2. Bleeding Disorders: These arise from abnormalities that prevent normal clot formation. Disseminated intraventricular coagulation (DIC) involves both widespread clotting and severe bleeding. Thrombocytopenia (1) is a condition in which the number of circulating platelets is deficient, which leads to spontaneous bleeding from small blood vessels all over the body. This leads to widespread hemorrhage and purple dots. A low platelet can indicate this. Impaired liver function (2) occurs when the liver is unable to synthesize its usual supply of procoagulants, abnormal, and often severe, bleeding occurs. This can range from a vitamin K

Describe the structure, function, and production of erythrocytes.

Erythrocytes: They are red blood cells. Structure: Erythrocytes are small, biconcave (spectrin), and anucleate (lack a nucleus). Erythrocytes contain hemoglobin and antioxidant enzymes (which maintain the plasma membrane and promote RBC shape). They are over 97% hemoglobin. Erythrocytes function: Erythrocytes function to transport respiratory gases (oxygen and carbon dioxide). Erythrocytes production: Blood cell formation is referred to as hematopoiesis, or hemopoiesis. This process occurs within the red bone marrow, which is composed largely of soft network of reticular connective tissues bordering on wide blood capillaries called blood sinusoids. That network has immature blood cells, macrophages, fat cells, and reticular cells (which secrete the fibers). This can be predominately found within the proximal epiphyses of the humerus or femur (bones of axial skeleton).

Describe the process of hemostasis, differentiation the intrinsic pathway from the extrinsic pathway.

Hemostasis: If a blood vessel wall breaks, a whole series of reaction will be set in motion to complete hemostasis, or stoppage of bleeding. It's a quick, localized, and carefully controlled. There are three steps. 1: vascular spasm, 2: platelet plug formation, and 3: coagulation (blood clotting). Blood loss at the site permanently prevented when fibrous tissue grows into the clot and seal the whole in the blood vessel. 1: Vascular spasm: The blood vessels respond by constricting (vasoconstriction). This will be triggered by direct injury to vascular smooth muscle, chemicals released by endothelial cells and platelets, and reflexes intimated by local pain receptors. 2: Platelet plug formation: Platelets play a key role by aggregating, forming a plug that temporarily seals the break in the vessel wall. Intact endothelial cells release nitric oxide and prostaglandin called prostacyclin. These prevent platelet aggregation in undamaged tissue. However, platelets adhere to collagen fibers. This process also deals with ADP (platelets sticking + releasing) with serotonin and thromboxane A2 (messengers than enhance). 3: Coagulation: Coagulation (blood clotting) reinforces the platelet plug with fibrin threads that act as a "molecular glue" for the aggregated platelets. Blood is transformed from a liquid to a gel in a multistep process that involves a series of substances called clotting factors, or procoagulants. They all normally circulate within the blood until mobilized. *Fibrinogen, prothrombin, calcium, fibrin. *Activation turns clotting factors into enzymes by clipping off a piece of the protein, causing it to change shape. Once one clotting factor is activated, it activates the following as a sequence. Coagulation occurs in THREE phases. Phase 1: Two pathways to prothrombin activator. A complex substance called prothrombin activator is formed. Phase 2: Common pathway to thrombin. Prothrombin activator converts a plasma protein called prothrombin into thrombin, an enzyme, Phase 3: Common pathway to the fibrin mesh. Thrombin catalyzes the joining of fibrinogen molecules present in plasma to a fibrin mesh, which traps blood cells and effectively seals the hole until the blood vessel can be repaired.

List factors that limit clot formation.

Homeostatic mechanisms prevent clots from becoming unnecessarily large. 1: Swift removal of clotting factors, and 2: inhibition of activated clotting factors. Other mechanisms block the final step in which fibrinogen is polymerized into fibrin. They work by restricting thrombin to the clot or by inactivating if it escaped into circulation. Clotting factors carried away from site by circulating blood (so clot doesn't get too big). Antithrombin III inactivated thrombin (slows down clotting process). Protein C inhibits intrinsic pathway events (limits the size of the clot as well). Heparin enhances activity of antithrombin III and inhibits intrinsic pathway events.

List the classes, structural characteristics, and functions of leukocytes.

Leukocytes: They are white blood cells with complete cells, nuclei, and the usual organelles. They are far less numerous than red blood cells. Structural characteristics of Leukocytes: They have cytoplasmic extensions called amoeboid motion. They follow the trail of molecules released by damaged cells or other leukocytes, called positive chemotaxis. They reproduce through leukocytosis and multiple within hours Functions of Leukocytes: They are crucial to our defense against disease. They form an army that helps protect the body from damages by bacteria, viruses, parasites, toxins, and tumor cells. White blood cells are able to slip out of the capillary blood cells and the circulatory system is their means of transport to areas of the body where they are needed to combat inflammation or immune responses. Classes of Leukocytes: (1) Granulocytes: Neutrophil, eosinophil, basophil. (2) Agranulocytes: Lymphocytes, monocyte. * Leukocytes need special cell adhesion molecules displayed by endothelial cells forming the capillary walls at sites of inflammation.

Describe: Leukopoiesis.

Leukopoiesis: Hemocytoblast give rise to myeloid stem cells and lymphoid stem cells. Granulocyte Leukopoiesis: 1. Myeloid stem cells become myeloblasts. 2. Myeloblasts accumulate lysosomes to become promyelocytes. 3. Promyelocytes differentiate into myelocytes. 4. Cell division stops and nuclei arch to form bands cells. 5. Nuclei constricts and segment to become mature granulocytes. *MYELOID > MYELOBLAST > PROMYELOCYTES > MYELOCYTES > BANDS + NUCLEI > GRANULOCYTES. Agranulocyte Leukopoiesis: 1. Myeloid stem cells become monoblasts. 2. Monoblasts become promonocytes. 3. Promonocytes leave bone marrow and become monocytes in lymph tissues. 4. Lymphoid stem cells become lymphoblasts. 5. Lymphoblasts become prolymphocytes. 6. Prolymphocytes leave bone marrow and become lymphocytes in lymph tissue. *MYELOID > MONOBLASTS > PROMONOCYTES > MONOCYTES > LYMPHOID > LYMPHOBLASTS > PROLYMPHOCYTES > LYMPHOCYTES.

Describe the structure, function, and formation of platelets.

Platelet structure: One-fourth of the diameter of a lymphocyte, they are cytoplasmic fragments of large cells called megakaryocytes. They have granules that contain chemical that act in the clotting process, including serotonin, CA2+, a variety of enzymes, ADP, and platelet-derived growth factor (PDGF). Platelet function: Platelets are essential for the clotting process that occurs in plasma who blood vessels are ruptured or their lining is injured. By sticking to the damaged site, platelets form a temporary plug that helps seal the break. In the meantime, they circulate freely, kept mobile but inactive by molecules (nitric oxide, prostacyclin) secreted by endothelial cells lining the blood vessels. Platelet formation: It's regulated by thrombopoietin. They are derived fro megakaryocytes, which are progeny of the hemocytoblast and the myeloid stem cell. Repeated mitoses of the megakaryobast occur, which press up against a sinusoid and sends cytoplasmic extensions through the sinusoid wall into the bloodstream. These extension rupture, which release platelet fragments. The plasma membranes associated with each fragment seat around the cytoplasm and forms the disc-shaped platelets.

List the functions of blood.

Summary: Delivers oxygen, transports metabolic wastes, transports hormones, maintains body temperature, maintains body pH, maintains fluid volume, prevents blood loss, and prevents infection. Distribution Functions: 1. Delivering oxygen from the lungs and nutrients from the digestive tract to all body cells. 2. Transporting metabolic waste products from cells to elimination sites (to the lung for elimination of carbon dioxide, and kidneys for disposal of nitrogenous wastes in urine). 3. Transporting hormones from the endocrine organs to their target organs. Regulatory Functions: 1. Maintaining appropriate body temperature by absorbing and distributing heat throughout the body and to the skin surface to encourage heat loss. 2. Maintaining normal pH in body tissues. Many blood proteins and other blood borne solutes act as buffers to prevent excessive or abrupt changes in blood pH that could jeopardize normal cell activities. Additionally, blood acts as the reservoir for the body's "alkaline reserve" of bicarbonate atoms. 3. Maintaining adequate fluid volume in the circulatory system. Salts (sodium chloride and others) and blood proteins act to prevent excessive fluid loss from the bloodstream into the tissue spaces. As a result, the fluid volume in the blood vessels remains ample to support efficient blood circulation to all parts of the body. Protective Functions: 1. Preventing blood loss. When a blood vessel is damaged, platelets, and plasma proteins initiate clot formation, halting blood loss. 2. Preventing infection. Drifting along in blood are antibodies, complement proteins, and white blood cells, all of which help defend the body against foreign invaders such as bacteria and viruses.

Give examples of disorders caused by abnormalities of each of the formed elements.

The formed elements: Blood, erythrocytes, leukocytes, and platelets. Blood abnormalities: Erythrocyte abnormalities: They can be classified as anemias or polycythemia. Anemias are conditions where blood has an abnormally low oxygen-carrying capacity. It's a sign of a disorder rather than a disease itself. It's a hallmark of blood oxygen levels that are inadequate to support normal metabolism. Anemias are the following: Hemorrhagic anemias (blood loss), hemolytic anemias (rupture or lyse prematurely), aplastic anemias (destruction of marrow by drugs). They can have low hemoglobin content with microcytes, which are small and pale, are produced. They can have pernicious anemia, with intrinsic factor and vitamin B deficiency, and macrocytes, which are large and pale. They can have abnormal hemoglobin, with thalassemia with absent or faulty globin chains. You can also have polycythemia. It's when an abnormal excess of erythrocytes that increase blood viscosity, causing the blood to sludge or flow sluggishly. They can have dizziness, high RBC count, or blood doping (induced polycythemia) for athletes. Leukocyte abnormalities: An overproduction of abnormal leukocytes occurs in leukemia and infectious mononucleosis. There's also leukopenia with an abnormally low white blood cell count, commonly caused by drugs. Leukemia refers to cancerous conditions. There's also infectious mononucleosis, which is a highly contagious viral disease. It has an excessive amount of agranulocytes. Platelet abnormalities:


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