Chapter 19: Blood

Plate plug formation phases:

1. Platelet adhesion 2. Platelet release reaction 3. Platelet aggregation

Anemia

A lower-than-normal number of RBCs, which is indicated by significant drop in hematocrit.

Agglutinogens

Antigens that occur in characteristic combinations

Components of blood

Blood Plasma Formed elements, which are cells and cell fragments

Function of Blood: Protection

Blood can clot (become gel-like), which protects against its excessive loss from the cardiovascular system after an injury. In addition, its white blood cells protect against disease by carrying on phagocytosis. Several types of blood proteins, including antibodies, interferons, and complement, help protect against disease in a variety of ways.

Regulatory Substances: Enzymes

Catalyze chemical reactions.

Thrombosis

Clotting in an unbroken blood vessel (usually a vein)

Fibrinogen

Description: Large protein. Function: Plays essential role in blood clotting.

Major histocompatibility (MHC) antigens,

Proteins protruding from their plasma membrane into the extracellular fluid. These "cell identity markers" are unique for each person (except identical twins). Although RBCs possess blood group antigens, they lack the MHC antigens.

Regulatory Substances: Hormones

Regulate metabolism, growth, and development.

Thrombus

The clot in a Thrombosis

Blood Plasma

The portion of blood consisting of water, proteins and other solutes. It is made up of of 91.5% and 8.5% solutes, most of the solute is made up of proteins.

Three general functions of Blood

Transportation Regulation Protection

Reticulocytes

(immature red blood cells) enter the circulation and mature in 1 to 2 days. Ultimately, a cell near the end of the development sequence ejects its nucleus and becomes a reticulocyte. Reticulocytes retain some mitochondria, ribosomes, and endoplasmic reticulum. They pass from red bone marrow into the bloodstream by squeezing between the endothelial cells of blood capillaries. Reticulocytes develop into mature red blood cells within 1 to 2 days after their release from red bone marrow.

Erythropoiesis

(production of red blood cells) begins in the red bone marrow. Main stimulus is hypoxia the production of RBCs, starts in the red bone marrow with a precursor cell called a proerythroblast. The proerythroblast divides several times, producing cells that begin to synthesize hemoglobin. Ultimately, a cell near the end of the development sequence ejects its nucleus and becomes a reticulocyte. Reticulocytes retain some mitochondria, ribosomes, and endoplasmic reticulum. They pass from red bone marrow into the bloodstream by squeezing between the endothelial cells of blood capillaries. Reticulocytes develop into mature red blood cells within 1 to 2 days after their release from red bone marrow.

Steps in the RBC Life Cycle

1, Macrophages in the spleen, liver, or red bone marrow phagocytize ruptured and worn-out red blood cells. 2. The globin and heme portions of hemoglobin are split apart. 3. Globin is broken down into amino acids, which can be reused to synthesize other proteins. 4. Iron is removed from the heme portion in the form of Fe³⁺, which associates with the plasma protein transferrin , a transporter for Fe³ in the bloodstream. 5. In muscle fibers, liver cells, and macrophages of the spleen and liver, Fe³⁺ detaches from transferrin and attaches to an iron-storage protein called ferritin (FER-i-tin). 6. On release from a storage site or absorption from the gastrointestinal tract, Fe³⁺ reattaches to transferrin. 7. The Fe³⁺-transferrin complex is then carried to red bone marrow, where RBC precursor cells take it up through receptormediated endocytosis for use in hemoglobin synthesis. Iron is needed for the heme portion of the hemoglobin molecule, and amino acids are needed for the globin portion. Vitamin B₁₂ is also needed for the synthesis of hemoglobin. 8. Erythropoiesis in red bone marrow results in the production of red blood cells, which enter the circulation. 9. When iron is removed from heme, the non-iron portion of heme is converted to biliverdin , a green pigment, and then into bilirubin , a yellow-orange pigment. 10. Bilirubin enters the blood and is transported to the liver. 11. Within the liver, bilirubin is released by liver cells into bile, which passes into the small intestine and then into the large intestine. 12. In the large intestine, bacteria convert bilirubin into urobilinogen. 13. Some urobilinogen is absorbed back into the blood, converted to a yellow pigment called urobilin , and excreted in urine. 14. Most urobilinogen is eliminated in feces in the form of a brown pigment called stercobilin, which gives feces its characteristic color.

Clotting stages

1. Two pathways, called the extrinsic pathway and the intrinsic pathway lead to the formation of prothrombinase. Once prothrombinase is formed, the steps involved in the next two stages of clotting are the same for both the extrinsic and intrinsic pathways, and together these two stages are referred to as the common pathway. 2. Prothrombinase converts prothrombin (a plasma protein formed by the liver) into the enzyme thrombin. 3. Thrombin converts soluble fibrinogen (another plasma protein formed by the liver) into insoluble fibrin. Fibrin forms the threads of the clot.

Embolus

A blood clot, bubble of air, fat from broken bones, or a piece of debris transported by the bloodstream An embolus that breaks away from an arterial wall may lodge in a smaller-diameter artery downstream and block blood flow to a vital organ.

Lymphocytes

A form of small leukocyte (white blood cells) with a single round nucleus, occurring especially in the lymphatic system. They can be identified by their large nucleus. They are are able to live for years while most other blood cells live for hours, days, or weeks. The number of red blood cells and platelets remains rather steady while that of white blood cells varies depending on invading pathogens and other foreign antigens The three major types of lymphocyte are: T cells, B cells and natural killer (NK) cells.

Blood clot

A gell that consists of a network of insoluble protein fibers called fibrin in which the formed elements of blood are trapped.

Red bone marrow

A highly vascularized connective tissue located in the microscopic spaces between trabeculae of spongy bone tissue. It is present chiefly in bones of the axial skeleton, pectoral and pelvic girdles, and the proximal epiphyses of the humerus and femur. Creates Pluripotent stem cells (hemocytoblasts) that make Blood cells.

Blood

A liquid connective tissue that consists of cells surrounded by a liquid extracellular matrix. The extracellular matrix is called blood plasma, and it suspends various cells and cell fragments.

Hemostasis (not HOMEOstasis)

A sequence of responses that stops bleeding. When blood vessels are damaged or ruptured, the hemostatic response must be quick, localized to the region of damage, and carefully controlled in order to be effective. Three mechanisms reduce blood loss: (1) vascular spasm, (2) platelet plug formation (3) blood clotting (coagulation).

Constituents of Plasma proteins

Albumins Globulins Fibrinogen

Red Blood Cells(RBCs)

Also called erthrocytes. Contain the oxygen-carrying protein hemoglobin, which is a pigment that gives whole blood its red color. A healthy adult male has about 5.4 million red blood cells per microliter of blood, and a healthy adult female has about 4.8 million. (One drop of blood is about 50 microliters.) To maintain normal numbers, new mature cells must enter the circulation at the astonishing rate of at least 2 million per second, a pace that balances the equally high rate of RBC destruction. Job is to transport oxygen from the lungs to body cells and deliver carbon dioxide from body cells to the lungs

White Blood Cells (WBCs)

Also called leukocytes.Their main function is to combat invading microbes. Protect the body from invading pathogens and other foreign substances. Leukocytes are classified as either granular (containing vesicles that appear when the cells are stained) or agranular (containing no granules). There are several types of WBCs: neutrophils, basophils, eosinophils, monocytes, and lymphocytes. Granular leukocytes: neutrophils, eosinophils, basophils Agranular leukocytes: lymphocytes, monocytes Lymphocytes are further subdivided into B lymphocytes (B cells), T lymphocytes (T cells), and natural killer (NK) cells. Each type of WBC contributes in its own way to the body's defense mechanisms.

Leukopenia

An abnormally low level of white blood cells (below 5000/microliters). It is never beneficial and may be caused by radiation, shock, and certain chemotherapeutic agents.

Plasmin (fibrinolysin)

An active plasma enzyme.Used to dissolve small, unwanted clots.

Heparin

An anticoagulant that is produced by mast cells and basophils, combines with antithrombin and increases its effectiveness in blocking thrombin.

Cytokines

Are small glycoproteins that are typically produced by cells such as red bone marrow cells, leukocytes, macrophages, fibroblasts, and endothelial cells. They generally act as local hormones. These glycoproteins stimulate proliferation of progenitor cells in red bone marrow and regulate the activities of cells involved in nonspecific defenses (such as phagocytes) and immune responses (such as B cells and T cells). Several different kinds regulate development of different blood cell types. Two important families of this type of glycoproteins that stimulate white blood cell formation are colony-stimulating factors (CSFs) and interleukins.

Hemolytic Disease of the Newborn (HDN)

At birth, small amounts of fetal blood leak into the maternal circulation. If the baby is Rh+ and the mother is Rh-, she will develop antibodies to the Rh factor. During her next pregnancy with an Rh+ baby, when she transfers antibodies to the fetus (a normal occurrence), transferred anti Rh antibodies will attack some of the fetus' red blood cells causing agglutination and hemolysis.

Myeloid stem cells

Begin their development in red bone marrow and give rise to red blood cells, platelets, monocytes, neutrophils, eosinophils, basophils, and mast cells.

Antithrombin,

Blocks the action of several factors, including XII, X, and II (prothrombin).

ABO blood group

Blood group based on two glycolipid antigens calledA and B (Figure 19.12). People whose RBCs display only antigen A have type A blood. Those who have only antigen B are type B. Individuals who have both A and B antigens are type AB; thosewho have neither antigen A nor B are type O.

Percent of blood plasma and percent of formed elements

Blood is about 45% formed elements and 55% blood plasma.

Blood groups

Blood is categorized based on the presence or absence of various antigens on the surface of red blood cells. There are 24 blood groups and more than 100 antigens Because these antigens are genetically controlled, blood types vary among different populations. Classification is based on antigens labeled A, B or AB with O being the absence of the antigens. An additional antigen, Rh, is present in 85% of humans.

agglutinins

Blood plasma usually contains antibodie that react with the A or B antigens if the two are mixed.

Hypoxia

Cellular oxygen deficiency, may occur if too little oxygen enters the blood. For example, the lower oxygen content of air at high altitudes reduces the amount of oxygen in the blood. Oxygen delivery may also fall due to anemia, which has many causes: Lack of iron, lack of certain amino acids, and lack of vitamin B12 are but a few (see Disorders: Homeostatic Imbalances at the end of this chapter). Circulatory problems that reduce blood flow to tissues may also reduce oxygen delivery. Whatever the cause, cellular oxygen deficiency stimulates the kidneys to step up the release of erythropoietin, which speeds the development of proerythroblasts into reticulocytes in the red bone marrow. As the number of circulating RBCs increases, more oxygen can be delivered to body tissues.

Function of Blood: Regulation

Circulating blood helps maintain homeostasis of all body fluids. Blood helps regulate pH through the use of buffers (chemicals that convert strong acids or bases into weak ones). It also helps adjust body temperature through the heat absorbing and coolant properties of the water in blood plasma and its variable rate of flow through the skin, where excess heat can be lost from the blood to the environment. In addition, blood osmotic pressure influences the water content of cells, mainly through interactions of dissolved ions and proteins.

Regulatory Substances: Vitamins

Cofactors for enzymatic reactions.

Hemeglobin

Consists of a protein called globin, composed of four polypeptide chains (two alpha and two beta chains); A ringlike nonprotein pigment called a heme is bound to each of the four chains. At the center of each heme ring is an iron ion (Fe²⁺) that can combine reversibly with one oxygen molecule, allowing each hemoglobin molecule to bind four oxygen molecules. Each oxygen molecule picked up from the lungs is bound to an iron ion. As blood flows through tissue capillaries, the iron-oxygen reaction reverses. Hemoglobin releases oxygen, which diffuses first into the interstitial fluid and then into cells. Hemoglobin also transports about 23% of the total carbon dioxide, a waste product of metabolism. (The remaining carbon dioxide is dissolved in plasma or carried as bicarbonate ions.) Blood flowing through tissue capillaries picks up carbon dioxide, some of which combines with amino acids in the globin part of hemoglobin. As blood flows through the lungs, the carbon dioxide is released from hemoglobin and then exhaled.

The amount of blood in the human body

Constitutes about 20% of extracellular fluid, amounting to 8% of the total body mass. The blood volume is 5 to 6 liters (1.5 gal) in an averagesized adult male and 4 to 5 liters (1.2 gal) in an average-sized adult female. The gender difference in volume is due to differences in body size.

Electrolytes

Description: Inorganic salts; positively charged (cations) Na⁺, K⁺, Ca²⁺, Mg²⁺, negatively charged (anions) Cl⁻, HPO₄²⁻, SO₄²⁻, HCO₃⁻. Function: Help maintain osmotic pressure and play essential roles in cell functions.

Globulins

Description: Large proteins (plasma cells produce immunoglobulins). Function: Immunoglobulins help attack viruses and bacteria. Alpha and beta globulins transport iron, lipids, and fat-soluble vitamins.

Water(91.5%)

Description: Liquid portion of blood. Function: Solvent and suspending medium. Absorbs, transports, and releases heat.

Plasma proteins

Description: Most produced by liver. Function: Responsible for colloid osmotic pressure. Major contributors to blood viscosity. Transport hormones (steroid), fatty acids, andcalcium. Help regulate blood pH.

Nutrients

Description: Products of digestion, such as amino acids, glucose, fatty acids, glycerol, vitamins, and minerals. Function: Essential roles in cell functions, growth, and development.

Albumins

Description: Smallest and most numerous plasma proteins. Function: Help maintain osmotic pressure, an important factor in the exchange of fluids across blood capillary walls.

Waste products

Description: Urea, uric acid, creatine, creatinine, bilirubin, ammonia. Function: Most are breakdown products of protein metabolism that are carried by the blood to organs of excretion.

Fibrinolysis

Dissolution of a clot

Platelet release reaction

Due to adhesion, the platelets become activated, and their characteristics change dramatically. They extend many projections that enable them to contact and interact with one another, and they begin to liberate the contents of their vesicles. Liberated ADP and thromboxane A2 play a major role by activating nearby platelets. Serotonin and thromboxane A2 function as vasoconstrictors, causing and sustaining contraction of vascular smooth muscle, which decreases blood flow through the injured vessel.

Progenitor cells

During hemopoiesis, some of the myeloid stem cells differentiate into these cells These cells are no longer capable of reproducing themselves and are committed to giving rise to more specific elements of blood. Some progenitor cells are known as colony-forming units (CFUs). Following the CFU designation is an abbreviation that indicates the mature elements in blood that they will produce: CFU-E ultimately produces erythrocytes (red blood cells); CFU-Meg produces megakaryocytes, the source of platelets; and CFU-GM ultimatelyproduces granulocytes (specifically, neutrophils) and monocytes. These cells, like stem cells, resemble lymphocytes and cannot be distinguished by their microscopic appearance alone.

Constituents of Other solutes

Electrolytes Nutrients Gases Regulatory substances Waste products

Clotting (Coagulation) Factors

Fibrinogen Prothrombin Tissue factor (thromboplastin) Calcium ions Proaccelerin, labile factor, or accelerator globulin (AcG). VII Serum prothrombin conversion accelerator (SPCA), stable factor, or proconvertin. Antihemophilic factor (AHF), antihemophilic factor A, or antihemophilic globulin (AHG). Christmas factor, plasma thromboplastin component (PTC), or antihemophilic factor B Stuart factor, Prower factor, or thrombokinase. Plasma thromboplastin antecedent (PTA) or antihemophilic factor C. Hageman factor, glass factor, contact factor, or antihemophilic factor D. Fibrin-stabilizing factor (FSF)

Carbonic anhydrase

Found in Red Blood Cells (RBCs). Catalyzes the conversion of carbon dioxide and water to carbonic acid. This compound transports about 70% of carbon dioxide in the plasma. It also servesas an important buffer in extracellular fluid.

Platelets

Fragments of cells that do not have a nucleus. Among other actions, they release chemicals that promote blood clotting when blood vessels are damaged. They are the functional equivalent of thrombocytes, nucleated cells found in lower vertebrates that prevent blood loss by clotting blood. Under the influence of the hormone thrombopoietin, hemopoietic stem cells differentiate into platelets. Only survive for only 5 to 9 days.

Lymphoid stem cells

Give rise to lymphocytes. Begin their development in red bone marrow but complete it in lymphatic tissues. They also give rise to natural killer (NK) cells. Although the various stem cells have distinctive cell identity markers in their plasma membranes, they cannot be distinguished histologically and resemble lymphocytes.

Rh blood group

Hamed because the Rh antigen, called Rh factor, was first found in the blood of the Rhesus monkey. Peoplewhose RBCs have Rh antigens are designated Rh⁺ (Rh positive); those who lack Rh antigens are designated Rh⁻ (Rh negative). Table 19.5 shows the incidence of Rh⁺ and Rh⁻ in various populations. Normally, blood plasma does not contain anti-Rh⁻ antibodies. If an Rh person receives an Rh⁺ blood transfusion, however, the immune system starts to make anti-Rh antibodies that will remain in the blood. If a second transfusion of Rh⁺blood is given later, the previously formed anti-Rh antibodies will cause agglutination and hemolysis of the RBCs in the donated blood, and a severe reaction may occur.

High count and low count of Basophils

High Count may indicate: Allergic reactions, leukemias, cancers, hypothyroidism. Low Count may indicate: Pregnancy, ovulation, stress, hypothyroidism.

High count and low count of Eosinophils

High Count may indicate: Allergic reactions, parasitic infections, autoimmune diseases. Low Count may indicate: Drug toxicity, stress, acute allergic reactions.

High count and low count of Neutrophils

High Count may indicate: Bacterial infection, burns, stress, inflammation. Low Count may indicate: Radiation exposure, drug toxicity, vitamin B12 deficiency, systemic lupus erythematosus (SLE).

High count and low count of Lymphocytes

High Count may indicate: Viral infections, some leukemias, infectious mononucleosis Low Count may indicate: Prolonged illness, HIV infection, immunosuppression, treatment with cortisol.

High count and low count of Monocytes

High Count may indicate: Viral or fungal infections, tuberculosis, some leukemias, other chronic diseases. Low Count may indicate: Bone marrow suppression, treatment with cortisol.

Platelet-derived Growth Factor (PDGF)

Hormone that can cause proliferation of vascular endothelial cells, vascular smooth muscle fibers, and fibroblasts to help repair damaged blood vessel walls.

Thrombosis

If blood clots too easily, the result is clotting in an undamaged blood vessel.

Gas: Oxygen (O₂)

Important in many cellular functions.

Agglutination

In an incompatible blood transfusion, antibodies in the recipient's plasma bind to the antigens on the donated RBCs which causes clumping of the RBCs.

Typing and cross-matching

In order to determine a person's blood type, typing and cross-matching are performed. A drop of blood is mixed with an antiserum that will agglutinate blood cells that possess agglutinogens that react with it.

Activated protein C (APC)

Inactivates the two major clotting factors not blocked by antithrombin and enhances activity of plasminogen activators. Babies that lack the ability to produce APC due to a genetic mutation usually die of blood clots in infancy.

Leukocytosis

Increase in the number of WBCs above 10,000/microliters, is a normal, protective response to stresses such as invading microbes, strenuous exercise, anesthesia, and surgery.

Type AB blood

Individuals who have both A and B antigens

Platelet adhesion

Initially, platelets contact and stick to parts of a damaged blood vessel, such as collagen fibers of the connective tissue underlying the damaged endothelial cells.

Gas: Carbon dioxide (CO₂)

Involved in the regulation of blood pH.

Erythropoietin (EPO)

It increases the number of red blood cell precursors. It is produced primarily by cells in the kidneys that lie between the kidney tubules (peritubular interstitial cells). With renal failure, this hormone release slows and RBC production is inadequate. This leads to a decreased hematocrit, which leads to a decreased ability to deliver oxygen to body tissues.

Thrombopoietin (TPO)

It is a hormone produced by the liver that stimulates the formation of platelets from megakaryocytes.

Main function of blood

It transports oxygen from the lungs and nutrients from the gastrointestinal tract, which diffuse from the blood into the interstitial fluid and then into body cells. Carbon dioxide and other wastes move in the reverse direction, from body cells to interstitial fluid to blood. It then transports the wastes to various organs—the lungs, kidneys, and skin—for elimination from the body.

Serum

Liquid seperated from the blood clot. Straw colored liquid, it is simply blood plasma minus the clotting proteins

Gas: Nitrogen(N₂)

No known function

Eosinophils

Number: 0.5-1% of all WBCs. Characteristics: 8-10 micrometers in diameter; nucleus has 2 lobes; large cytoplasmic granules appear deep blue-purple. Functions: Combat effects of histamine in allergic reactions, phagocytize antigen-antibody complexes, and destroy certain parasitic worms.

Monocytes

Number: 150,000-400,000 microliters Characteristics: 12-20 micrometers in diameter; nucleus is kidney-or horseshoe-shaped; cytoplasm is blue-gray and appears foamy. Functions: Phagocytosis (after transforming into fixed or wandering macrophages).

Basophils

Number: 20-25% of all WBCs. Characteristics: Small lymphocytes are 6-9 micrometers in diameter; large lymphocytes are 10-14 micrometers in diameter; nucleus is round or slightly indented; cytoplasm forms rim around nucleus that looks sky blue; the larger the cell, the more cytoplasm is visible. Functions: Liberate heparin, histamine, and serotonin in allergic reactions that intensify overall inflammatory response.

Lymphocytes (T cells, B cells, and natural killer cells)

Number: 3-8% of all WBCs. Characteristics: Small lymphocytes are 6-9 micrometers in diameter; large lymphocytes are 10-14 micrometers in diameter; nucleus is round or slightly indented; cytoplasm forms rim around nucleus that looks sky blue; the larger the cell, the more cytoplasm is visible. Functions: Mediate immune responses, including antigen-antibody reactions. B cells develop into plasma cells, which secrete antibodies. T cells attack invading viruses, cancer cells, and transplanted tissue cells. Natural killer cells attack wide variety of infectious microbes and certain spontaneously arising tumor cells.

Neutrophils

Number: 60-70% of all WBCs. Characteristics: 10-12 micrometers diameter; nucleus has 2-5 lobes connected by thin strands of chromatin; cytoplasm has very fine, pale lilac granules. Functions: Phagocytosis. Destruction of bacteria with lysozyme, defensins, and strong oxidants, such as superoxide anion, hydrogen peroxide, and hypochlorite anion.

Fibrinogen

Number: I Location:Liver. Pathway: Common.

II Prothrombin. Liver. Common.

Number: II . Location: Liver Pathway: Common.

III Tissue factor (thromboplastin). Damaged tissues and activated platelets. Extrinsic.

Number: III Location: Damaged tissues and activated platelets. Pathway: Extrinsic.

IV Calcium ions (Ca2). Diet, bones, and platelets. All.

Number: IV Location: Diet, bones, and platelets. Pathway: All.

IX Christmas factor, plasma thromboplastin component (PTC), or antihemophilic factor B Liver. Intrinsic.

Number: IX Location: Liver. Pathway: Intrinsic.

V Proaccelerin, labile factor, or accelerator globulin (AcG). Liver and platelets. Extrinsic and intrinsic.

Number: V Location: Liver and platelets. Pathway: Extrinsic and intrinsic.

VII Serum prothrombin conversion accelerator (SPCA), stable factor, or proconvertin. Liver. Extrinsic.

Number: VII Location: Liver. Pathway: Extrinsic.

VIII Antihemophilic factor (AHF), antihemophilic factor A, or antihemophilic globulin (AHG). Liver. Intrinsic.

Number: VIII Location: Liver. Pathway: Intrinsic.

X Stuart factor, Prower factor, or thrombokinase. Liver. Extrinsic and intrinsic.

Number: X Location: Liver. Pathway: Extrinsic and intrinsic.

XI Plasma thromboplastin antecedent (PTA) or antihemophilic factor C. Liver. Intrinsic.

Number: XI Location: Liver. Pathway: Intrinsic.

XII Hageman factor, glass factor, contact factor, or antihemophilic factor D. Liver. Intrinsic.

Number: XII Location: Liver. Pathway: Intrinsic.

XIII Fibrin-stabilizing factor (FSF).

Number: XIII Location: Liver and platelets Pathway: Common

Clotting (Coagulation) Factors All

Number| Names| Source| Pathways ------------------------------ I Fibrinogen. Liver. Common. II Prothrombin. Liver. Common. III Tissue factor (thromboplastin). Damaged tissues and activated platelets. Extrinsic. IV Calcium ions (Ca2). Diet, bones, and platelets. All. V Proaccelerin, labile factor, or accelerator globulin (AcG). Liver and platelets. Extrinsic and intrinsic. VII Serum prothrombin conversion accelerator (SPCA), stable factor, or proconvertin. Liver. Extrinsic. VIII Antihemophilic factor (AHF), antihemophilic factor A, or antihemophilic globulin (AHG). Liver. Intrinsic. IX Christmas factor, plasma thromboplastin component (PTC), or antihemophilic factor B Liver. Intrinsic. X Stuart factor, Prower factor, or thrombokinase. Liver. Extrinsic and intrinsic. XI Plasma thromboplastin antecedent (PTA) or antihemophilic factor C. Liver. Intrinsic. XII Hageman factor, glass factor, contact factor, or antihemophilic factor D. Liver. Intrinsic. XIII Fibrin-stabilizing factor (FSF).

Precursor cells also known as blasts

Over several cell divisions they develop into the actual formed elements of blood. For example, monoblasts develop into monocytes, eosinophilic myeloblasts develop into eosinophils, and so on. Precursor cells have recognizable microscopic appearances.

Type A blood

People whose RBCs display only antigen A

Red Blood Cell (RBC) anatomy

RBCs are biconcave discs with a diameter of 7-8 micrometers. Mature red blood cells have a simple structure. Their plasma membrane is both strong and flexible, which allows them to deform without rupturing as they squeeze through narrow blood capillaries. Certain glycolipids in the plasma membrane of RBCs are antigens that account for the various blood groups such as the ABO and Rh groups. RBCs lack a nucleus and other organelles and can neither reproduce nor carry on extensive metabolic activities. The cytosol of RBCs contains hemoglobin molecules; these important molecules are synthesized before loss of the nucleus during RBC production and constitute about 33% of the cell's weight.

Red Blood Cell (RBC) Physiology

Red blood cells are highly specialized for their oxygen transport function. Because mature RBCs have no nucleus, all of their internal space is available for oxygen transport. Because RBCs lack mitochondria and generate ATP anaerobically (without oxygen), they do not use up any of the oxygen they transport. Even the shape of an RBC facilitates its function. A biconcave disc has a much greater surface area for the diffusion of gas molecules into and out of the RBC than would, say, a sphere or a cube. Each RBC contains about 280 million hemoglobin molecules.

RBC Life Cycle

Red blood cells live only about 120 days because of the wear and tear their plasma membranes undergo as they squeeze through blood capillaries. Dead cells are removed from the circulation by the spleen and liver. Breakdown products from the cells are recycled and reused.

Hemopoietic growth factors

Several hormones that regulate the differentiation and proliferation of particular progenitor cells.

Cord-blood transplant

Stem cells collected from an umbilical cord after birth are frozen and may also be used and have advantages over bone marrow transplants.

Anticoagulants

Substances that delay, suppress, or prevent blood clotting. They are present in blood. Some are: antithrombin, Heparin, and Activated protein C (APC)

Formed elements

The cellular components of blood, which include red blood cells(RBCs) or erythrocytes, white blood cells(WBCs) or leukocytes, and platelets

Interstitial fluid

The fluid that bathes body cells and is constantly renewed by the blood

Common Pathway

The formation of prothrombinase marks the beginning of this pathway. In the second stage of blood clotting (Figure 19.11c), prothrombinase and Ca²⁺ catalyze the conversion of prothrombin to thrombin. In the third stage, thrombin, in the presence of Ca²⁺, converts fibrinogen, which is soluble, to loose fibrin threads, which are insoluble. Thrombin also activates factor XIII (fibrin stabilizing factor), which strengthens and stabilizes the fibrin threads into a sturdy clot. Plasma contains some factor XIII, which is also released by platelets trapped in the clot. Thrombin has two positive feedback effects. In the first positive feedback loop, which involves factor V, it accelerates the formation of prothrombinase. Prothrombinase in turn accelerates the production of more thrombin, and so on. In the second positive feedback loop, thrombin activates platelets, which reinforces their aggregation and the release of platelet phospholipids.

Hemoglobin's role in regulating blood flow and blood pressure

The gaseous hormone nitric oxide(NO), produced by the endothelial cells that line blood vessels, binds to hemoglobin. Under some circumstances, hemoglobin releases nitric oxide. The released nitric oxidecauses vasodilation, an increase in blood vessel diameter that occurs when the smooth muscle in the vessel wall relaxes. Vasodilation improves blood flow and enhances oxygen delivery to cells near the site of NO release.

Neutrophil.

The granules of a neutrophil are smaller than those of other granular leukocytes, evenly distributed, and pale lilac. Because the granules do not strongly attract either the acidic (red) or basic (blue) stain, these WBCs are neutrophilic (neutral loving).The nucleus has two to five lobes, connected by very thin strands of nuclear material. As the cells age, the number of nuclear lobes increases. Because older neutrophils thus have several differently shaped nuclear lobes, they are often called polymorphonuclear leukocytes (PMNs), polymorphs, or "polys."

Eosinophil.

The large, uniform-sized granules within an eosinophil are eosinophilic — they stain red-orange with acidic dyes. The granules usually do not cover or obscure the nucleus, which most often has two lobes connected by either a thin strand or a thick strand of nuclear material.

Hemorrhage

The loss of a large amount of blood from the vessels.

Lymphocyte

The nucleus of a lymphocyte (LIM-foˉ-sı¯t) stains dark and is round or slightly indented . The cytoplasm stains sky blue and forms a rim around the nucleus. The larger the cell, the more cytoplasm is visible. Lymphocytes are classified by cell diameter as large lymphocytes (10- 14 micrometers) or small lymphocytes (6-9 micrometers). Although the functional significance of the size difference between small and large lymphocytes is unclear, the distinction is still clinically useful because an increase in the number of large lymphocytes has diagnostic significance in acute viral infections and in some immunodeficiency diseases.

Monocyte.

The nucleus of a monocyte ( is usually kidney-shaped or horseshoe-shaped, and the cytoplasm is blue-gray and has a foamy appearance. The cytoplasm's color and appearance are due to very fine azurophilic granules, which are lysosomes. Blood is merely a conduit for monocytes, which migrate from the blood into the tissues,where they enlarge and differentiate into macrophages. Some become fixed (tissue) macrophages, which means they reside in a particular tissue; examples are alveolar macrophages in the lungs or macrophages in the spleen. Others become wandering macrophages, which roam the tissues and gather at sites of infection or inflammation.

Polycythemia

The percentage of RBCs is abnormally high, and the hematocrit may be 65% or higher. This raises the viscosity of blood, which increases the resistance to flow and makes the blood more difficult for the heart to pump. Increased viscosity also contributes to high blood pressure and increased risk of stroke. Causes of polycythemia include abnormal increases in RBC production, tissue hypoxia, dehydration, and blood doping or the use of EPO by athletes.

Hematocrit

The percentage of total blood volume occupied by RBCs. A hematocrit of 40 indicates that 40% of the volume of blood is composed of RBCs. The normal range of hematocrit for adult females is 38-46% (average = 42); for adult males, it is 40-54% (average = 47). The hormone testosterone, present in much higher concentration in males than in females, stimulates synthesis of erythropoietin (EPO), the hormone that in turn stimulates production of RBCs. Thus, testosterone contributes to higher hematocrits in males. Lower values in women during their reproductive years also may be due to excessive loss of blood during menstruation.

Clotting or coagulation

The process of gel formation (forming blood clots). It is a series of chemical reactions that culminates in formation of fibrin threads.

Hemopoiesis(hematopoiesis)

The process of producing blood cells. The process by which the formed elements of blood developis called hemopoiesis or hematopoiesis. Before birth, hemopoiesis first occurs in the yolk sac of an embryo and later in the liver, spleen, thymus, and lymph nodes of a fetus. Red bone marrow becomes the primary site of hemopoiesis in the last 3 months before birth, and continues as the source of blood cells after birth and throughout life.

Basophil.

The round, variable-sized granules of a basophil are basophilic (basic loving)—they stain blue-purple with basic dyes. The granules commonly obscure the nucleus, which has two lobes.

Antigens

The surfaces of erythrocytes contain a genetically determined assortment of glycoproteins and glycolipids. Based on the presence or absence of various antigens, blood is categorized into different blood groups.

Pluripotent stem cells or hemocytoblasts

These cells have the capacity to develop into many different types of cells. Differentiate into each of the different types of blood cells. About 0.05-0.1% of red bone marrow cells. are are derived from mesenchyme (tissue from which almost all connective tissues develop). In order to form blood cells, pluripotent stem cells in red bone marrow produce two further types of stem cells, which have the capacity to develop into several types of cells. These stem cells are called myeloid stem cells and lymphoid stem cells.

Clotting (coagulation)factors.

These factors include calcium ions , several inactive enzymes that are synthesized by hepatocytes (liver cells) and released into the bloodstream, and various molecules associated with platelets or released by damaged tissues. Most clotting factors are identified by Roman numerals that indicate the order of their discovery (not necessarily the order of their participation inn the clotting process). It is divided into pathways(stages): 1. Extrinsic pathway 2. Intrinsic pathway 3. Common pathway

Extrinsic pathway

This clotting has fewer steps than the intrinsic pathway and occurs rapidly—within a matter of seconds if trauma is severe. It is so named because a tissue protein called tissue factor (TF), also known as thromboplastin, leaks into the blood from cells outside (extrinsic to) blood vessels and initiates the formation of prothrombinase. TF is a complex mixture of lipoproteins and phospholipids released from the surfaces of damaged cells. In the presence of Ca²⁺, TF begins a sequence of reactions that ultimately activates clotting factor X (Figure 19.11a). Once factor X is activated, it combines with factor V in the presence of Ca2 to form the active enzyme prothrombinase, completing the extrinsic pathway.

Intrinsic pathway

This clotting is more complex than the extrinsic pathway, and it occurs more slowly, usually requiring several minutes. The intrinsic pathway is so named because its activators are either in direct contact with blood or contained within (intrinsic to) the blood; outside tissue damage is not needed. If endothelial cells become roughened or damaged, blood can come in contact with collagen fibers in the connective tissue around the endothelium of the blood vessel. In addition, trauma to endothelial cells causes damage to platelets, resulting in the release of phospholipids by the platelets. Contact with collagen fibers (or with the glass sides of a blood collection tube) activates clotting factor XII (Figure 19.11b), which begins a sequence of reactions that eventually activates clotting factor X. Platelet phospholipids and Ca²⁺ can also participate in the activation of factor X. Once factor X is activated, it combines with factor V to form the active enzyme prothrombinase (just as occurs in the extrinsic pathway), completing the intrinsic pathway.

Type O blood

Those who have neither antigen A nor B

Type B blood

Those who have only antigen B

Elevation of in the white blood count

Usually indicates an infection or inflammation.

Constituents of blood

Water(91.5%) Plasma Proteins(7%) Other Solutes(1.5%)

Plasminogen

When a clot is formed, an inactive plasma enzyme called is incorporated into the clot.

Pulmonary Embolism

When an embolus lodges in the lungs.

Vascular spasm

When arteries or arterioles are damaged, the circularly arranged smooth muscle in their walls contracts immediately. This reduces blood loss for several minutes to several hours, during which time the other hemostatic mechanisms go into operation. The spasm is probably caused by damage to the smooth muscle, by substances released from activated platelets, and by reflexes initiated by pain receptors.

Invasion

When bacteria, microbe, or some other foreign body enters the human body.

Polycythemia

When hematocrit(the volume percentage of red blood cells in blood) is less than 55 percent.

Emigration or diapedesis

When white blood cells leave the bloodstream and collect at sites of invasion. During Emigration they roll along the endothelium, stick to it, and then squeeze between endothelial cells . The precise signals that stimulate emigration through a particular blood vessel vary for the different types of WBCs. Molecules known as adhesion molecules help WBCs stick to the endothelium.

Erythropoietin

a hormone released by the kidneys in response to hypoxia (lowered oxygen concentration) stimulates differentiation of hematopoietic stem cells into erythrocytes.

Blood protects

against excessive loss by clotting and against infections through the use of white blood cells.

anti-A antibody

agglutinins antibodies which reacts with antigen A

anti-B antibody

agglutinins antibodies which reacts with antigen B

Fibrinolytic system

dissolves small, inappropriate clots; it also dissolves clots at a site of damage once the damage is repaired.

Blood regulates

homeostasis of all body fluids, pH, body temperature and water content of cells.

Megakaryocytes

in red bone marrow splinter into 2000-3000 fragments to create the platelets that contain many vesicles but no nucleus.

Disorders: Homeostatic Imbalances: Sickle cell disease

is a genetic anemia (oxygen-carrying capacity of the blood is reduced). The RBC are thin and shaped like crescents or sickles. The red blood cells of individuals with this disease contain hemoglobin-S (Hb-S) that causes red blood cells to bend into a sickle shape when it gives up oxygen to the interstitial fluid.

Vitamin K

is needed for normal clot formation although it is not directly involved. It is used in the synthesis of 4 clotting factors.

Clot retraction

is the consolidation or tightening of the fibrin clot. The fibrin threads attached to the damaged surfaces of the blood vessel gradually contract as platelets pull on them. As the clot retracts, it pulls the edges of the damaged vessel closer together, decreasing the risk of further damage. During retraction, some serum can escape between the fibrin threads, but the formed elements in blood cannot. Normal retraction depends on an adequate number of platelets in the clot, which release factor XIII and other factors, thereby strengthening and stabilizing the clot. Permanent repair of the blood vessel can then take place. In time, fibroblasts form connective tissue in the ruptured area, and new endothelial cells repair the vessel lining.

Transfusion

is the transfer of whole blood or blood components (red blood cells only or blood plasma only) into the bloodstream or directly into the red bone marrow. A transfusion is most often given to alleviate anemia, to increase blood volume (for example, after a severe hemorrhage), or to improve immunity.

Agranular leukocytes

lymphocytes, monocytes

Granular leukocytes

neutrophils, eosinophils, basophils

Differential white blood cell count

or "diff", a count of each of the five types of white blood cells, to detect infection or inflammation, determine the effects of possible poisoning by chemicals or drugs, monitor blood disorders (for example, leukemia) and the effects of chemotherapy, or detect allergic reactions and parasitic infections. Because each type of white blood cell plays a different role, determining the percentage of each type in the blood assists in diagnosing the condition.

Blood transports

oxygen, carbon dioxide, nutrients, hormones, heat and waste products.

Bone marrow transplants

performed to replace cancerous red bone marrow with normal red bone marrow. The donor's marrow is usually collected from the iliac crest of the hip bone.

Antibodies or immunoglobulins

produced during certain immune responses. Foreign substances (antigens) such as bacteria and viruses stimulate production of millions of different antibodies. These gamma globulins binds specifically to the antigen that stimulated its production and thus disables the invading antigen.

Hemolysis

rupture of the RBCs