BLOOD



BLOOD

Blood Functions

• Transports

1. Dissolved gasses

2. Nutrients

3. Waste products to lungs and kidneys

4. Enzymes

5. Hormones from endocrine organs

• Regulates

1. pH

2. Electrolyte concentration of body fluids

3. Body temperature

• Restricts fluid loss

• Defends pathogens and toxins

Overview of Blood Circulation

•      Blood leaves the heart via arteries that branch repeatedly until they become capillaries

•      Oxygen (O2) and nutrients diffuse across capillary walls and enter tissues

•      Carbon dioxide (CO2) and wastes move from tissues into the blood

•      Oxygen-deficient blood leaves the capillaries and flows in veins to the heart

•      This blood flows to the lungs where it releases CO2 and picks up O2

•      The oxygen-rich blood returns to the heart

Composition of Blood

•      Blood is the body’s only fluid tissue

•      It is composed of liquid plasma and formed elements

•      Formed elements include:

•    Erythrocytes, or red blood cells (RBCs)

•    Leukocytes, or white blood cells (WBCs)

•    Platelets

Physical Characteristics and Volume

•      Blood is a sticky, opaque fluid with a metallic taste

•      Color varies from scarlet (oxygen-rich) to dark red (oxygen-poor)

•      The pH of blood is 7.35–7.45

•      Temperature is 38(C, slightly higher than “normal” body temperature

•      Blood accounts for approximately 8% of body weight

•      Average volume of blood is 5–6 L for males, and 4–5 L for females

Distribution

Blood transports:

•    Oxygen from the lungs and nutrients from the digestive tract

•    Metabolic wastes from cells to the lungs and kidneys for elimination

•    Hormones from endocrine glands to target organs

Regulation

Blood maintains:

•    Appropriate body temperature by absorbing and distributing heat

•    Normal pH in body tissues using buffer systems

•    Adequate fluid volume in the circulatory system

Protection

Blood prevents blood loss by:

•    Activating plasma proteins and platelets

•    Initiating clot formation when a vessel is broken

Blood prevents infection by:

•    Synthesizing and utilizing antibodies

•    Activating complement proteins

•    Activating WBCs to defend the body against foreign invaders

Blood Plasma

• Plasma accounts for 55 % of the volume of whole blood.

• 92% of plasma is water, the rest consists of electrolytes and dissolved organic compounds.

• The exchange of dissolved materials occurs by diffusion across the walls of capillaries.

• The dissolved concentration of gases, nutrients, and waste products differs, depending on the region sampled and the metabolic state of the tissue and individual.

Blood plasma contains over 100 solutes, including:

•    Proteins – albumin, globulins, clotting proteins, and others

•    Nonprotein nitrogenous substances – lactic acid, urea, creatinine

•    Organic nutrients – glucose, carbohydrates, amino acids

•    Electrolytes – sodium (Na+), potassium (K+), calcium (Ca++), chloride (Cl-), bicarbonate (HCO3-)

•    Respiratory gases – oxygen and carbon dioxide

The Plasma Proteins:

1. Albumin, the most abundant plasma protein, contributes to the osmotic pressure of the blood and provides a transport mechanism for specific insoluble or valuable materials in the blood.

2. Globular proteins are important in binding and transporting hormones, lipids (lipoproteins), and metal ions. The immunoglobulins (antibodies) are proteins that attack foreign proteins and pathogens.

3. Under the proper stimulation, fibrinogen molecules aggregate to form large insoluble strands of fibrin that establish the basis for a blood clot. The removal of fibrinogen from plasma leaves a fluid called serum.

Formed Elements

•      Erythrocytes, leukocytes, and platelets make up the formed elements

•    Only WBCs are complete cells

•    RBCs have no nuclei or organelles, and platelets are just cell fragments

•      Most formed elements survive in the bloodstream for only a few days

•      Most blood cells do not divide but are renewed by cells in bone marrow

Erythrocytes (RBCs)

• Biconcave discs & anucleate allow for a huge surface area to volume ratio

• Hematocrit – percentage of RBCs out of the total blood volume. (Ave) 46 adult men & 42 adult women.

• There are roughly 5 million RBCs in each microliter of blood; they transport oxygen and carbon dioxide, and have large surface-to volume ratios.

• Red blood cells account for slightly less than half the blood volume.

• Erythrocytes are unable to perform normal maintenance operations and usually degenerate after about 120 days in the circulation.

• Each red blood cell contains molecules of hemoglobin (Hgb), a globular protein formed from four subunits. Each subunit contains a single molecule of heme, which can reversibly bind oxygen.

• Heme molecules bind to oxygen when plasma concentrations are high; the oxygen is released when plasma concentrations decline.

• Carbon dioxide molecules can be bound to the globin portion of the hemoglobin molecule.

• Damaged or expired red blood cells are recycled by phagocytes. The proteins are disassembled into amino acids, and the iron gets bound to transferrins for transport to the bone marrow and liver. The heme units are not recycled, but removed from the circulation by the liver and excreted in the bile.

• Agglutinogens A, B, and D (Rh) on the exposed surfaces of the red blood cells determine an individual's blood type. Agglutinins within the plasma will react with red blood cells bearing different agglutinogens.

• Anti-Rh agglutinins are only synthesized after an Rh-negative individual becomes sensitized to the Rh agglutinogen. (During pregnancy)

• Testing for compatibility involves the determination of blood type and a cross-match test.

• Standard blood typing detects the A, B, and D (Rh) agglutinogens. The most common blood type used for transfusion is O-negative (universal donor). AB-positive (Universal recipient)

Hemoglobin (Hgb) [pic]

Hemoglobin is composed of:

•    The protein globin, made up of two alpha and two beta chains, each bound to a heme group

•    Each heme group bears an atom of iron, which can bind one to oxygen molecule

•      Each hemoglobin molecule can transport four molecules of oxygen

•      Oxyhemoglobin – hemoglobin bound to oxygen

•    Oxygen loading takes place in the lungs

• Deoxyhemoglobin- hemoglobin after oxygen diffuses into tissues (reduced Hgb)

Carboxyhemoglobin – hemoglobin bound to carbon dioxide

•    Carbon dioxide loading takes place in the tissues

•      The fetus forms HbF, which has a higher affinity for oxygen than adult hemoglobin

Production of Blood Cells

•      Hematopoiesis – blood cell formation

•      Hematopoiesis occurs in the red bone marrow of the:

•    Axial skeleton and girdles

•    Epiphyses of the humerus and femur

•      Hemocytoblasts give rise to all formed elements

• Circulating stem cells give rise to embryonic blood cells which migrate into the liver, spleen, thymus, and bone marrow.

• Hemocytoblasts divide to give rise to several populations of stem cells. The divisions of these cells produce the various blood cells throughout life.

Erythropoiesis

• Erythropoiesis primarily occurs within red marrow of the sternum, vertebrae, skull, scapulae, pelvis, and proximal limb bones.

• Red blood cell formation increases under erythropoietin stimulation. This hormone is released from the kidneys when they are not receiving adequate supplies of oxygen.

• Erythropoiesis is hormonally controlled and depends on adequate supplies of iron, amino acids, and B vitamins

• Stages in red blood cell development include erythroblasts and reticulocytes. Reticulocytes (immature RBC’s) usually account for 0.8 percent of circulating red blood cells.

• Circulating erythrocytes – the number remains constant and reflects a balance between RBC production and destruction

• Too few red blood cells leads to tissue hypoxia

• Too many red blood cells causes undesirable blood viscosity

Hormonal Control of Erythropoiesis

Erythropoietin (EPO) release by the kidneys is triggered by:

•    Hypoxia due to decreased RBCs

•    Decreased oxygen availability

•    Increased tissue demand for oxygen

Enhanced erythropoiesis increases the:

•    RBC count in circulating blood

•    Oxygen carrying ability of the blood increases

Erythropoiesis: Nutrient Requirements

•      Erythropoiesis requires:

•    Proteins, lipids, and carbohydrates

•    Iron, vitamin B12, and folic acid

•      The body stores iron in Hgb (65%), the liver, spleen, and bone marrow

•      Intracellular iron is stored in protein-iron complexes such as ferritin and hemosiderin

•      Circulating iron is loosely bound to the transport protein transferrin

Fate and Destruction of Erythrocytes

•      The life span of an erythrocyte is 100–120 days

•      Old erythrocytes become rigid and fragile, and their hemoglobin begins to degenerate

•      Dying erythrocytes are engulfed by macrophages

•      Heme and globin are separated and the iron is salvaged for reuse

Fate of Hemoglobin

•      Heme is degraded to a yellow pigment called bilirubin

•      The liver secretes bilirubin into the intestines as bile

•      The intestines metabolize it into urobilinogen

•      This degraded pigment leaves the body in feces, in a pigment called stercobilin

or as urobilinogen in urine

•      Globin is metabolized into amino acids and is released into the circulation

Erythrocyte Disorders

Anemia – blood has abnormally low oxygen-carrying capacity

•    It is a symptom rather than a disease itself

•    Blood oxygen levels cannot support normal metabolism

•    Signs/symptoms include fatigue, paleness, shortness of breath, and chills

Anemia: Insufficient Erythrocytes

•      Hemorrhagic anemia – result of acute or chronic loss of blood (e.g.Trauma & Menstruation)

•      Hemolytic anemia – prematurely ruptured erythrocytes

•      Aplastic anemia – destruction or inhibition of red bone marrow

Anemia: Decreased Hemoglobin Content

Iron-deficiency anemia results from:

• A secondary result of hemorrhagic anemia

• Inadequate intake of iron-containing foods

• Impaired iron absorption

Pernicious anemia results from:

•    Deficiency of vitamin B12

•      Often caused by lack of intrinsic factor needed for absorption of B12

Anemia: Abnormal Hemoglobin

Thalassemias – absent or faulty globin chain in hemoglobin

•    Erythrocytes are thin, delicate, & deficient in hemoglobin

Sickle-cell anemia – results from a defective gene coding for an abnormal hemoglobin called hemoglobin S (HbS)

Polycythemia

Polycythemia – excess RBCs that increase blood viscosity

•      Blood doping in athletics

Leukocytes (WBCs)

• White blood cells are components of the immune system that defends the body against pathogens, toxins, wastes, and abnormal or damaged cells and tissues.

• There are 6,000-9,000 white blood cells in each microliter of whole blood .

• Normal response to bacterial or viral invasion

• Move through tissue spaces

• Granular leukocytes include neutrophils, eosinophils , and basophils.

• Neutrophils are abundant, highly mobile phagocytes. Eosinophils (less common) are attracted to foreign compounds coated with antibodies. Basophils (rare) migrate into damaged tissues and release histamine, aiding in the inflammation response.

• Monocytes migrating into peripheral tissues become free macrophages.

• Lymphocytes, cells of the lymphatic system, include T cells and B cells. T cells migrate to peripheral tissues and attack foreign or abnormal cells; B cells produce antibodies.

White Blood Cell Formation

• Granulocytes and monocytes are produced by stem cells in the bone marrow

• Lymphocytes are produced in bone marrow, thymus, spleen, and other lymphoid tissues.

Classification of Leukocytes:

Granulocytes (Neutrophils, eosinophils, & basophils)

•    Contain cytoplasmic granules that stain specifically with Wright’s stain

•    Are larger and usually shorter-lived than RBCs

•    Have lobed nuclei

•    Are all phagocytic cells

Neutrophils (Polymorphonuclear) (60-70% of WBC’s)

•      Neutrophils have two types of granules that:

•    Take up both acidic and basic dyes

•    Give the cytoplasm a lilac color

•    Contain peroxidases, hydrolytic enzymes, and defensins (antibiotic-like proteins)

•      Neutrophils are our body’s bacterial slayers

Lifespan : 1 day in blood; 1-2 days in tissue

Eosinophils (1-4% of WBC’s)

•      Eosinophils account for 1–4% of WBCs

•    Have red-staining, bi-lobed nuclei connected via a broad band of nuclear material

•    Have red to crimson (acidophilic) large, coarse, lysosome-like granules

•    Lead the body’s counterattack against parasitic worms

•    Lessen the severity of allergies by phagocytizing immune complexes

Lifespan: 1 day in blood; weeks in tissue

Basophils (0.5-1% of WBC’s)

•    Have U( or S(shaped nuclei with two or three conspicuous constrictions

•    Are functionally similar to mast cells

•    Have large, purplish-black (basophilic) granules that contain histamine

Histamine – inflammatory chemical that acts as a vasodilator & attracts other WBCs

Lifespan: 1 day in blood; hours in tissue

Agranulocytes (Lymphocytes & monocytes)

•    Lack visible cytoplasmic granules

•    Are similar structurally, but are functionally distinct and unrelated cell types

•    Have spherical (lymphocytes) or kidney-shaped (monocytes) nuclei

Lymphocytes (20-25% of WBC’s)

Have large, dark-purple, circular nuclei with a thin rim of blue cytoplasm

•      Found mostly enmeshed in lymphoid tissue (some circulate in the blood)

•      There are two types of lymphocytes: T cells and B cells

•    T cells function in the immune response

•    B cells give rise to plasma cells, which produce antibodies

Lifespan: Years

Monocytes (3-8% of WBC’s)

•    They are the largest leukocytes

•    They have abundant pale-blue cytoplasms

•    They have purple staining, U- or kidney-shaped nuclei

•    They leave the circulation, enter tissue, and differentiate into macrophages

Lifespan: Days in blood; years in tissue

Macrophages:

•    Are highly mobile and actively phagocytic

•    Activate lymphocytes to mount an immune response

Leukocyte Disorders: Leukemias

Leukemia refer to cancerous conditions involving white blood cells

Leukemias are named according to the abnormal white blood cells involved

Immature white blood cells are found in the bloodstream in all leukemias

Bone marrow becomes totally occupied with cancerous leukocytes

The white blood cells produced, though numerous, are not functional

• Death is caused by internal hemorrhage and overwhelming infections

Acute leukemia involves blast-type cells and primarily affects children

Chronic leukemia is more prevalent in older people

Common symptoms of leukemia:

• Anemia      

• Fever

• Weakness and fatigue

• Frequent infections

• Loss of appetite and/or weight

• Swollen or tender lymph nodes, liver, or spleen

• Easy bleeding or bruising

• Tiny red spots (called petechiae) under the skin

• Swollen or bleeding gums

• females. Sweating, especially at night; and/or

• Bone or joint pain.

Platelets

Megakaryocytes in the bone marrow release packets of cytoplasm, called platelets, into the circulating blood. There are 150,000-500,000 platelets in each microliter of whole blood.

•   Platelet granules contain serotonin, Ca2+, enzymes, ADP, and platelet-derived growth factor (PDGF)

•      Platelets function in the clotting mechanism by forming a temporary plug that helps seal breaks in blood vessels

Hemostasis (A series of reactions designed for stoppage of bleeding)

During hemostasis, three phases occur in rapid sequence

1. Vascular spasms – immediate vasoconstriction in response to injury

2. Platelet plug formation

3. Coagulation (blood clotting)

Platelet Plug Formation

•   Platelets do not stick to each other or to the endothelial lining of blood vessels

Upon damage to a blood vessel, platelets:

•    Stick to exposed collagen fibers and form a platelet plug

•    Release serotonin and ADP, which attract still more platelets

•       The platelet plug is limited to the immediate area of injury by PGI

Coagulation: A set of reactions in which blood is transformed from a liquid to a gel

The coagulation phase occurs as factors released by endothelial cells (extrinsic pathway) and platelets (intrinsic pathway) interact with clotting factors to yield thromboplastin. Thromboplastin triggers the conversion of prothrombin to thrombin, and thrombin catalyzes the formation of fibrin from circulating plasma fibrinogen.This results in the formation of a blood clot.

• The blood clot gradually retracts (syneresis), pulling the damaged surfaces together. As repairs proceed the clot dissolves (fibrinolysis) through the action of plasmin, the activated form of circulating plasminogen.

• The coagulation process requires calcium ions, and Vitamin K must be available for the synthesis of five of the clotting factors.

• Excessive or inappropriate clotting can lead to the formation of a thrombus or an embolus. Anticoagulant drugs include heparin and coumadin; in some cases clots may be dissolved by activating plasminogen with streptokinase, urokinase, or tissue plasminogen activator.

Hemostasis Disorders: Thromboembolytic Disorders

Thrombus – a clot that develops and persist in an unbroken blood vessel

•    Thrombi can block circulation, resulting in tissue death

•    Coronary thrombosis – thrombus in blood vessel of the heart

Embolus – a thrombus freely floating in the blood stream

•    Pulmonary emboli can impair the ability of the body to obtain oxygen

•    Cerebral emboli can cause strokes

Prevention of Undesirable Clots

Substances used to prevent undesirable clots include:

•    Aspirin

•    Heparin

•    Warfarinin (Coumadin)

•    Flavonoids – substances found in tea, red wine, and grape juice that have natural anticoagulant activity

Hemostasis Disorders: Bleeding Disorders

Thrombocytopenia – condition where the number of circulating platelets is deficient

•    Patients show petechiae (small purple blotches on the skin) due to spontaneous, widespread hemorrhage

•    Caused by suppression or destruction of bone marrow (e.g., malignancy, radiation)

•    Platelet counts less than 50,000/mm3 is diagnostic for this condition

•    Treated with whole blood transfusions

•      Inability to synthesize procoagulants by the liver results in severe bleeding disorders

•      Causes can range from vitamin K deficiency to hepatitis and cirrhosis

•      Inability to absorb fat can lead to vitamin K deficiencies as it is a fat-soluble substance and is absorbed along with fat

•      Liver disease can also prevent the liver from producing bile, which is required for fat and vitamin K absorption

•      Hemophilias – hereditary bleeding disorders caused by lack of clotting factors

•    Hemophilia A – most common type (83% of all cases) due to a deficiency of factor VIII

•    Hemophilia B – results from a deficiency of factor IX

•    Hemophilia C – mild type, caused by a deficiency of factor XI

•      Symptoms include prolonged bleeding and painful and disabled joints

•      Treatment is with blood transfusions and the injection of missing factors

Blood Transfusions

Transfusions are necessary:

•    When substantial blood loss occurs

Whole blood transfusions are used:

•    When blood loss is substantial

•    In treating thrombocytopenia

Packed red cells (cells with plasma removed) are used to treat anemia

Human Blood Groups

•      RBC membranes have glycoprotein antigens on their external surfaces

•      These antigens are:

•    Unique to the individual

•    Recognized as foreign if transfused into another individual

•    Promoters of agglutination and are referred to as agglutinogens

•      Presence/absence of these antigens are used to classify blood groups

•      The antigens of the ABO and Rh blood groups cause vigorous transfusion reactions when they are improperly transfused

ABO Blood Groups

•      The ABO blood groups consists of:

•    Two antigens (A and B) on the surface of the RBCs

•    Two antibodies in the plasma (anti-A and anti-B)

The following list, from The American National Red Cross, shows the percentage of people in the United States with a particular blood type..

O Positive - 38.4%

A Positive - 32.3%

B Positive - 9.4%

O Negative - 7.7%

A Negative - 6.5%

AB Positive - 3.2%

B Negative - 1.7%

AB Negative - 0.7%

• Cross-matching involves exposing donor RBCs to the recipient's plasma to detect other possible cross reactions.

Rh Blood Groups

•      Presence of the Rh agglutinogens on RBCs is indicated as Rh+

•      Anti-Rh antibodies are not spontaneously formed in Rh– individuals

•      However, if an Rh– individual receives Rh+ blood, anti-Rh antibodies form

•      A second expose to Rh+ blood will result in a typical transfusion reaction

Hemolytic Disease of the Newborn (Erythroblastosis fetalis)

•      Rh+ antibodies of a sensitized Rh– mother cross the placenta and attack and destroy the RBCs of an Rh+ baby

•      Rh– mother become sensitized when Rh+ blood (from a previous pregnancy of an Rh+ baby or a Rh+ transfusion) causes her body to synthesis Rh+ antibodies

•      The drug RhoGAM can prevent the Rh– mother from becoming sensitized

Transfusion Reactions

•      Transfusion reactions occur when mismatched blood is infused

•      Donor’s cells are attacked by the recipient’s plasma agglutinins causing:

•    Diminished oxygen-carrying capacity

•    Clumped cells that impede blood flow

•    Ruptured RBCs that release free hemoglobin into the bloodstream

•      Circulating hemoglobin precipitates in the kidneys and causes renal failure

Blood Typing

•      When serum containing anti-A or anti-B agglutinins is added to blood, agglutination will occur between the agglutinin and the corresponding agglutinogens

•      Positive reactions indicate agglutination

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