Make your own free website on Tripod.com

Chapter Notes for Lecture: E.N. Marieb, HUMAN ANATOMY & PHYSIOLOGY,5TH Edition, , Benjamine Cummings Publisher, 2001

Prepare from : V.A. Austin’s PowerPpoint Presentation (ISBN: 0-8053-5469-7), CD ROM: Pearson Education, Inc. , 2003.ter 19

 

Blood

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

•      Hematocrit – the percentage of RBCs out of the total blood volume

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

Functions of Blood

•      Blood performs a number of functions dealing with:

•    Substance distribution

•    Regulation of blood levels of particular substances

•    Body protection

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

•      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, potassium, calcium, chloride, bicarbonate

•    Respiratory gases – oxygen and carbon dioxide

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, essentially no organelles

•      Filled with hemoglobin (Hb), a protein that functions in gas transport

•      Contain the plasma membrane protein spectrin that:

•    Gives erythrocytes their flexibility

•    Allows them to change shape as necessary

•      Erythrocytes are an example of the complementarity of structure and function

•      Structural characteristics that contribute to its gas transport function are:

•    Biconcave shape that has a huge surface area to volume ratio

•    Discounting water content, erythrocytes are 97% hemoglobin

•    ATP is generated anaerobically, so the erythrocytes do not consume the oxygen they transport

Erythrocyte Function

•      Erythrocytes are dedicated to respiratory gas transport

•      Hemoglobin reversibly binds with oxygen and most oxygen in the blood is bound to hemoglobin

•      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

Hemoglobin (Hb)

•      Oxyhemoglobin – hemoglobin bound to oxygen

•    Oxygen loading takes place in the lungs

•      Deoxyhemoglobin – hemoglobin after oxygen diffuses into tissues (reduced Hb)

•      Carbaminohemoglobin – hemoglobin bound to carbon dioxide

•    Carbon dioxide loading takes place in the tissues

Production of Blood Cells

•      Hematopoiesis – blood cell formation

•      Hemopoiesis 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

Production of Erythrocytes: Erythropoiesis

•      A hemocytoblast is transformed into a committed cell called the proerythroblast

•      Proerythroblasts develop into early erythroblasts

•      The developmental pathway consists of three phases

•    Phase 1 – ribosome synthesis in early erythroblasts

•    Phase 2 – hemoglobin accumulation in late erythroblasts and normoblasts

•    Phase 3 – ejection of the nucleus from normoblasts and formation of reticulocytes

•      Reticulocytes then become mature erythrocytes

•      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

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

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 Hb (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

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

Life Cycle of Red Blood Cells

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

•      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, and deficient in hemoglobin

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

•    HbS has a single amino acid substitution in the beta chain

•    This defect causes RBCs to become sickle-shaped in low oxygen situations

Polycythemia

•      Polycythemia – excess RBCs that increase blood viscosity

•      Three main polycythemias are:

•    Polycythemia vera

•    Secondary polycythemia

•    Blood doping

Leukocytes (WBCs)

•      Leukocytes, the only blood components that are complete cells:

•    Are less numerous than RBCs

•    Make up 1% of the total blood volume

•    Can leave capillaries via diapedesis

•    Move through tissue spaces

•      Leukocytosis – WBC count over 11,000 per cubic millimeter

•    Normal response to bacterial or viral invasion

Classification of Leukocytes: Granulocytes

•      Granulocytes – neutrophils, eosinophils, and basophils

•    Contain cytoplasmic granules that stain specifically (acidic, basic, or both) with Wright’s stain

•    Are larger and usually shorter-lived than RBCs

•    Have lobed nuclei

•    Are all phagocytic cells

Neutrophils

•      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

Eosinophils

•      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

Basophils

•      Account for 0.5% of WBCs and:

•    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 and attracts other WBCs

Agranulocytes

•      Agranulocytes – lymphocytes and 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

•      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

Monocytes

•      Monocytes account for 4–8% of leukocytes

•    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

•      Macrophages:

•    Are highly mobile and actively phagocytic

•    Activate lymphocytes to mount an immune response

Production of Leukocytes

•      Leukopoiesis is hormonally stimulated by two families of cytokines (hematopoetic factors) – interleukins and colony-stimulating factors (CSFs)

•    Interleukins are numbered (e.g., IL-1, IL-2), whereas CSFs are named for the WBCs they stimulate (e.g., granulocyte-CSF stimulates granulocytes)

•      Macrophages and T cells are the most important sources of cytokines

•      Many hematopoietic hormones are used clinically to stimulate bone marrow

Formation of Leukocytes

•      All leukocytes originate from hemocytoblasts

•      Hemocytoblasts differentiate into myeloid stem cells and lymphoid stem cells

•      Myeloid stem cells become myeloblasts or monoblasts

•      Lymphoid stem cells become lymphoblasts

•      Myeloblasts develop into eosinophils, neutrophils, and basophils

•      Monoblasts develop into monocytes

•      Lymphoblasts develop into lymphocytes

Leukocyte Disorders: Leukemias

•      Leukemia refer to cancerous conditions involving white blood cells

•      Leukemias are named according to the abnormal white blood cells involved

•    Myelocytic leukemia – involves myeloblasts

•    Lymphocytic leukemia – involves lymphocytes

•      Acute leukemia involves blast-type cells and primarily affects children

•      Chronic leukemia is more prevalent in older people

Leukemia

•      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

•      Treatments include irradiation, antileukemic drugs, and bone marrow transplants

Platelets

•      Platelets are fragments of megakaryocytes with a blue-staining outer region and a purple granular center

•      The 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

Genesis of Platelets

•      The stem cell for platelets is the hemocytoblast

•      The sequential developmental pathway is hemocytoblast, megakaryoblast, promegakaryocyte, megakaryocyte, and platelets

Hemostasis

•      A series of reactions designed for stoppage of bleeding

•      During hemostasis, three phases occur in rapid sequence

•    Vascular spasms – immediate vasoconstriction in response to injury

•    Platelet plug formation

•    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:

•      Are stimulated by thromboxane A2

•    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 PGI2

Coagulation

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

•      Coagulation follows intrinsic and extrinsic pathways

Coagulation

•      The final thee steps of this series of reactions are:

•    Prothrombin activator is formed

•    Prothrombin is converted into thrombin

•    Thrombin catalyzes the joining of fibrinogen into a fibrin mesh

Detailed Reactions of Hemostasis

Coagulation Phase 1: Two Pathways to Prothrombin Activator

•      May be initiated by either the intrinsic or extrinsic pathway

•    Triggered by tissue-damaging events

•    Involves a series of procoagulants

•    Each pathway cascades toward factor X

•      Once factor X has been activated, it complexes with calcium ions, PF3, and factor V to form prothrombin activator

Coagulation Phase 2: Pathway to Thrombin

•      Prothrombin activator catalyzes the transformation of prothrombin to the active the enzyme thrombin

Coagulation Phase 3: Common Pathways to the Fibrin Mesh

•      Thrombin catalyzes the polymerization of fibrinogen into fibrin

•      Insoluble fibrin strands form the structural basis of a clot

•      Fibrin causes plasma to become a gel-like trap

•      Fibrin in the presence of calcium ions activates factor XIII that:

•    Cross-links fibrin

•    Strengthens and stabilizes the clot

Clot Retraction and Repair

•      Clot retraction – stabilization of the clot by squeezing serum from the fibrin strands

•      Repair

•    Platelet-derived growth factor (PDGF) stimulates rebuilding of blood vessel wall

•    Fibroblasts form a connective tissue patch

•    Endothelial cells multiply and restore the endothelial lining

Factors Limiting Clot Growth or Formation

•      Two homeostatic mechanisms prevent clots from becoming large

•    Swift removal of clotting factors

•    Inhibition of activated clotting factors

Inhibition of Clotting Factors

•      Fibrin acts as an anticoagulant by binding thrombin and preventing its:

•    Positive feedback effects of coagulation

•    Ability to speed up the production of prothrombin activator via factor V

•    Acceleration of the intrinsic pathway by activating platelets

•      Thrombin not absorbed to fibrin is inactivated by antithrombin III

•      Heparin, another anticoagulant, also inhibits thrombin activity

Factors Preventing Undesirable Clotting

•      Unnecessary clotting is prevented by the structural and molecular characteristics of endothelial cells lining the blood vessels

•      Platelet adhesion is prevented by:

•    The smooth endothelial lining of blood vessels

•    Heparin and PGI2 secreted by endothelial cells

•    Vitamin E quinone, a potent anticoagulant

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 – an antiprostaglandin that inhibits thromboxane A2

•    Heparin – an anticoagulant used clinically for pre- and postoperative cardiac care

•    Warfarinin – used for those prone to atrial fibrillation

•    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

Hemostasis Disorders: Bleeding Disorders

•      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

•    In certain hemostatis disorders

•      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

•      Humans have 30 varieties of naturally occurring RBC antigens

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

•      Other blood groups (M, N, Dufy, Kell, and Lewis) are mainly used for legalities

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)

•      An individual with ABO blood may have various types of antigens and spontaneously preformed antibodies

•      Agglutinogens and their corresponding antibodies cannot be mixed without serious hemolytic reactions

Rh Blood Groups

•      There are eight different Rh agglutinogens, three of which (C, D, and E) are common

•      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

•      Hemolytic disease of the newborn – 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

•      Treatment of hemolytic disease of the newborn involves pre-birth transfusions and exchange transfusions after birth

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

Plasma Volume Expanders

•      When shock is imminent from low blood volume, volume must be replaced

•      Plasma or plasma expanders can be administered

•      Plasma expanders:

•    Have osmotic properties that directly increase fluid volume

•    Are used when plasma is not available

•    Examples: purified human serum albumin, plasminate and dextran

•      Isotonic saline can also be used to replace lost blood volume

Diagnostic Blood Tests

•      Laboratory examination of blood can assess an individual’s state of health

•      Microscopic examination:

•    Variations in size and shape of RBCs – predictions of anemias

•    Type and number of WBCs – diagnostic of various diseases

•      Chemical analysis can provide a comprehensive picture of one’s general health status in relation to normal values

Developmental Aspects

•      Before birth, blood cell formation takes place in the fetal yolk sac, liver, and spleen

•      By the 7th month, red bone marrow is the primary hematopoietic area

•      Blood cells develop from mesenchymal cells called blood islands

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

Developmental Aspects

•      Age-related blood problems result from disorders of the heart, blood vessels, and the immune system

•      Increased leukemias are thought to be due to the waning deficiency of the immune system

•      Abnormal thrombus and embolus formation reflects the progress of atherosclerosis