04 May 2009

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

0 comments:

All links posted here are collected from various websites. No video or powerpoint files are uploaded on this blog. If you are the original author and do not wish to display your content on this blog please Email me anandkumarreddy at gmail dot com I will remove it. The contents of this blog are meant for educational purpose and not for commercial use. If you use any content give due credit to the original author.

This site uses cookies from Google to deliver its services, to personalise ads and to analyse traffic. Information about your use of this site is shared with Google. By using this site, you agree to its use of cookies.

  © Blogger templates Newspaper III by Ourblogtemplates.com 2008

Back to TOP