Blood - Anatomy & Physiology

Blood - Anatomy & Physiology
Presentation lecture by:Elaine N. Marieb
PowerPoint® Lecture Slides prepared by Vince Austin, University of Kentucky
Elaine N. Marieb
Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings


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:
o Erythrocytes, or red blood cells (RBCs)
o Leukocytes, or white blood cells (WBCs)
o Platelets
* Hematocrit – the percentage of RBCs out of the total blood volume

Components of Whole Blood
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:
o Substance distribution
o Regulation of blood levels of particular substances
o Body protection
Distribution

* Blood transports:
o Oxygen from the lungs and nutrients from the digestive tract
o Metabolic wastes from cells to the lungs and kidneys for elimination
o Hormones from endocrine glands to target organs

Regulation

* Blood maintains:
o Appropriate body temperature by absorbing and distributing heat
o Normal pH in body tissues using buffer systems
o Adequate fluid volume in the circulatory system

Protection

* Blood prevents blood loss by:
o Activating plasma proteins and platelets
o Initiating clot formation when a vessel is broken
* Blood prevents infection by:
o Synthesizing and utilizing antibodies
o Activating complement proteins
o Activating WBCs to defend the body against foreign invaders

Blood Plasma

* Blood plasma contains over 100 solutes, including:
o Proteins – albumin, globulins, clotting proteins, and others
o Nonprotein nitrogenous substances – lactic acid, urea, creatinine
o Organic nutrients – glucose, carbohydrates, amino acids
o Electrolytes – sodium, potassium, calcium, chloride, bicarbonate
o Respiratory gases – oxygen and carbon dioxide

Formed Elements

* Erythrocytes, leukocytes, and platelets make up the formed elements
o Only WBCs are complete cells
o 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 and other proteins that:
o Give erythrocytes their flexibility
o Allow them to change shape as necessary

* Erythrocytes are an example of the complementarity of structure and function
* Structural characteristics contribute to its gas transport function
o Biconcave shape that has a huge surface area relative to volume
o Discounting water content, erythrocytes are more than 97% hemoglobin
o 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 to one oxygen molecule
* Each hemoglobin molecule can transport four molecules of oxygen

Structure of Hemoglobin
Hemoglobin

* Oxyhemoglobin – hemoglobin bound to oxygen
o Oxygen loading takes place in the lungs
* Deoxyhemoglobin – hemoglobin after oxygen diffuses into tissues (reduced Hb)
* Carbaminohemoglobin – hemoglobin bound to carbon dioxide
o Carbon dioxide loading takes place in the tissues

Production of Erythrocytes

* Hematopoiesis – blood cell formation
* Hematopoiesis occurs in the red bone marrow of the:
o Axial skeleton and girdles
o 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
o Phase 1 – ribosome synthesis in early erythroblasts
o Phase 2 – hemoglobin accumulation in late erythroblasts and normoblasts
o Phase 3 – ejection of the nucleus from normoblasts and formation of reticulocytes
* Reticulocytes then become mature erythrocytes
Production of Erythrocytes: Erythropoiesis

* Circulating erythrocytes – the number remains constant and reflects a balance between RBC production and destruction
o Too few red blood cells leads to tissue hypoxia
o 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



Regulation and Requirements for Erythropoiesis
Hormonal Control of Erythropoiesis

* Erythropoietin (EPO) release by the kidneys is triggered by:
o Hypoxia due to decreased RBCs
o Decreased oxygen availability
o Increased tissue demand for oxygen
* Enhanced erythropoiesis increases the:
o RBC count in circulating blood
o Oxygen carrying ability of the blood
Erythropoietin Mechanism
Dietary Requirements of Erythropoiesis
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
* 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
* Hb released into the blood is captured by haptoglobin and phagocytized

Life Cycle of Red Blood Cells
* Anemia – blood has abnormally low oxygen-carrying capacity
o It is a symptom rather than a disease itself
o Blood oxygen levels cannot support normal metabolism
o Signs/symptoms include fatigue, paleness, shortness of breath, and chills

Erythrocyte Disorders
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
* Iron-deficiency anemia results from:
o A secondary result of hemorrhagic anemia
o Inadequate intake of iron-containing foods
o Impaired iron absorption
* Pernicious anemia results from:
o Deficiency of vitamin B12
o Lack of intrinsic factor needed for absorption of B12
* Treatment is intramuscular injection of B12; application of Nascobal
Anemia: Decreased Hemoglobin Content
Anemia: Abnormal Hemoglobin

* Thalassemias – absent or faulty globin chain in hemoglobin
o 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)
o HbS has a single amino acid substitution in the beta chain
o This defect causes RBCs to become sickle-shaped in low oxygen situations
Polycythemia

* Polycythemia – excess RBCs that increase blood viscosity
* Three main polycythemias are:
o Polycythemia vera
o Secondary polycythemia
o Blood doping

Leukocytes (WBCs)

* Leukocytes, the only blood components that are complete cells:
o Are less numerous than RBCs
o Make up 1% of the total blood volume
o Can leave capillaries via diapedesis
o Move through tissue spaces
* Leukocytosis – WBC count over 11,000 per cubic millimeter
o Normal response to bacterial or viral invasion

Granulocytes

* Granulocytes – neutrophils, eosinophils, and basophils
o Contain cytoplasmic granules that stain specifically (acidic, basic, or both) with Wright’s stain
o Are larger and usually shorter-lived than RBCs
o Have lobed nuclei
o Are all phagocytic cells
* Neutrophils have two types of granules that:
o Take up both acidic and basic dyes
o Give the cytoplasm a lilac color
o Contain peroxidases, hydrolytic enzymes, and defensins (antibiotic-like proteins)
* Neutrophils are our body’s bacteria slayers
Neutrophils
* Eosinophils account for 1–4% of WBCs
o Have red-staining, bilobed nuclei connected via a broad band of nuclear material
o Have red to crimson (acidophilic) large, coarse, lysosome-like granules
o Lead the body’s counterattack against parasitic worms
o Lessen the severity of allergies by phagocytizing immune complexes
* Account for 0.5% of WBCs and:
o Have U- or S-shaped nuclei with two or three conspicuous constrictions
o Are functionally similar to mast cells
o Have large, purplish-black (basophilic) granules that contain histamine
+ Histamine – inflammatory chemical that acts as a vasodilator and attracts other WBCs (antihistamines counter this effect)

Basophils
* Agranulocytes – lymphocytes and monocytes:
o Lack visible cytoplasmic granules
o Are similar structurally, but are functionally distinct and unrelated cell types
o Have spherical (lymphocytes) or kidney-shaped (monocytes) nuclei

Agranulocytes
* Account for 25% or more of WBCs and:
o Have large, dark-purple, circular nuclei with a thin rim of blue cytoplasm
o Are found mostly enmeshed in lymphoid tissue (some circulate in the blood)
* There are two types of lymphocytes: T cells and B cells
o T cells function in the immune response
o B cells give rise to plasma cells, which produce antibodies
Lymphocytes
* Monocytes account for 4–8% of leukocytes
o They are the largest leukocytes
o They have abundant pale-blue cytoplasms
o They have purple-staining, U- or kidney-shaped nuclei
o They leave the circulation, enter tissue, and differentiate into macrophages
Monocytes

* Macrophages:
o Are highly mobile and actively phagocytic
o Activate lymphocytes to mount an immune response
Summary of Formed Elements
* Leukopoiesis is hormonally stimulated by two families of cytokines (hematopoietic factors) – interleukins and colony-stimulating factors (CSFs)
o 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

Production 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

Formation of Leukocytes
* Leukemia refers to cancerous conditions involving white blood cells
* Leukemias are named according to the abnormal white blood cells involved
o Myelocytic leukemia – involves myeloblasts
o Lymphocytic leukemia – involves lymphocytes
* Acute leukemia involves blast-type cells and primarily affects children
* Chronic leukemia is more prevalent in older people

Leukocytes Disorders: Leukemias

* 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
Leukemia
* Platelets are fragments of megakaryocytes with a blue-staining outer region and a purple granular center
* Their 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
* Platelets not involved in clotting are kept inactive by NO and prostaglandin I2

Platelets
Genesis of Platelets

* The stem cell for platelets is the hemocytoblast
* The sequential developmental pathway is hemocytoblast, megakaryoblast, promegakaryocyte, megakaryocyte, and platelets
* A series of reactions designed for stoppage of bleeding
* During hemostasis, three phases occur in rapid sequence
o Vascular spasms – immediate vasoconstriction in response to injury
o Platelet plug formation
o Coagulation (blood clotting)
Hemostasis
* Platelets do not stick to each other or to the endothelial lining of blood vessels
* Upon damage to blood vessel endothelium (which exposes collagen) platelets:
o With the help of von Willebrand factor (VWF) adhere to collagen
o Are stimulated by thromboxane A2
o Stick to exposed collagen fibers and form a platelet plug
o Release serotonin and ADP, which attract still more platelets
* The platelet plug is limited to the immediate area of injury by PGI2

Platelet Plug Formation
* A set of reactions in which blood is transformed from a liquid to a gel
* Coagulation follows intrinsic and extrinsic pathways
* The final three steps of this series of reactions are:
o Prothrombin activator is formed
o Prothrombin is converted into thrombin
o Thrombin catalyzes the joining of fibrinogen into a fibrin mesh
Coagulation
Detailed Events of Coagulation

* May be initiated by either the intrinsic or extrinsic pathway
o Triggered by tissue-damaging events
o Involves a series of procoagulants
o 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 1: Two Pathways to Prothrombin Activator
* Prothrombin activator catalyzes the transformation of prothrombin to the active enzyme thrombin
Coagulation Phase 2: Pathway to Thrombin

* 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:
o Cross-links fibrin
o Strengthens and stabilizes the clot
Coagulation Phase 3: Common Pathways to the Fibrin Mesh
* Clot retraction – stabilization of the clot by squeezing serum from the fibrin strands
* Repair
o Platelet-derived growth factor (PDGF) stimulates rebuilding of blood vessel wall
o Fibroblasts form a connective tissue patch
o Stimulated by vascular endothelial growth factor (VEGF), endothelial cells multiply and restore the endothelial lining

Clot Retraction and Repair

* Two homeostatic mechanisms prevent clots from becoming large
o Swift removal of clotting factors
o Inhibition of activated clotting factors

Factors Limiting Clot Growth or Formation
* Fibrin acts as an anticoagulant by binding thrombin and preventing its:
o Positive feedback effects of coagulation
o Ability to speed up the production of prothrombin activator via factor V
o 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



Inhibition of Clotting Factors




* Unnecessary clotting is prevented by the structural and molecular characteristics of endothelial cells lining the blood vessels
* Platelet adhesion is prevented by:
o The smooth endothelial lining of blood vessels
o Heparin and PGI2 secreted by endothelial cells
o Vitamin E quinone, a potent anticoagulant

Factors Preventing Undesirable Clotting

* Thrombus – a clot that develops and persists in an unbroken blood vessel
o Thrombi can block circulation, resulting in tissue death
o Coronary thrombosis – thrombus in blood vessel of the heart

Hemostasis Disorders:
Thromboembolytic Conditions

* Embolus – a thrombus freely floating in the blood stream
o Pulmonary emboli can impair the ability of the body to obtain oxygen
o Cerebral emboli can cause strokes

Hemostasis Disorders:
Thromboembolytic Conditions
* Substances used to prevent undesirable clots include:
o Aspirin – an antiprostaglandin that inhibits thromboxane A2
o Heparin – an anticoagulant used clinically for pre- and postoperative cardiac care
o Warfarin – used for those prone to atrial fibrillation

Prevention of Undesirable Clots
* Disseminated Intravascular Coagulation (DIC): widespread clotting in intact blood vessels
* Residual blood cannot clot
* Blockage of blood flow and severe bleeding follows
* Most common as:
o A complication of pregnancy
o A result of septicemia or incompatible blood transfusions

Hemostasis Disorders

* Thrombocytopenia – condition where the number of circulating platelets is deficient
o Patients show petechiae (small purple blotches on the skin) due to spontaneous, widespread hemorrhage
o Caused by suppression or destruction of bone marrow (e.g., malignancy, radiation)
o Platelet counts less than 50,000/mm3 is diagnostic for this condition
o 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
o Hemophilia A – most common type (83% of all cases) due to a deficiency of factor VIII
o Hemophilia B – results from a deficiency of factor IX
o 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
* Whole blood transfusions are used:
o When blood loss is substantial
o In treating thrombocytopenia
* Packed red cells (cells with plasma removed) are used to treat anemia

Blood Transfusions
* RBC membranes have glycoprotein antigens on their external surfaces
* These antigens are:
o Unique to the individual
o Recognized as foreign if transfused into another individual
o Promoters of agglutination and are referred to as agglutinogens
* Presence or absence of these antigens is used to classify blood groups

Human 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

* The ABO blood groups consists of:
o Two antigens (A and B) on the surface of the RBCs
o 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

ABO 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 exposure to Rh+ blood will result in a typical transfusion reaction

Rh Blood Groups

* 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 becomes 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

Hemolytic Disease of the Newborn
* Transfusion reactions occur when mismatched blood is infused
* Donor’s cells are attacked by the recipient’s plasma agglutinins causing:
o Diminished oxygen-carrying capacity
o Clumped cells that impede blood flow
o Ruptured RBCs that release free hemoglobin into the bloodstream
* Circulating hemoglobin precipitates in the kidneys and causes renal failure

Transfusion Reactions
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
* Plasma expanders
o Have osmotic properties that directly increase fluid volume
o Are used when plasma is not available
o Examples: purified human serum albumin, plasminate, and dextran
* Isotonic saline can also be used to replace lost blood volume

* Laboratory examination of blood can assess an individual’s state of health
* Microscopic examination:
o Variations in size and shape of RBCs – predictions of anemias
o 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
Diagnostic Blood Tests

Blood.ppt