chapter 17: blood 1 17 blood (rbc). chapter 17: blood 2 overview of blood circulation blood leaves...

Chapter 17: Blood 1

17Blood

(RBC)

Chapter 17: Blood 2

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

Chapter 17: Blood 3

Overview of Blood Circulation

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

Chapter 17: Blood 4

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

Chapter 17: Blood 5

Components of Whole Blood

Figure 17.1

Withdraw blood and place in tube

1 2 Centrifuge

Plasma(55% of whole blood)

Formed elements

Buffy coat:leukocyctes and platelets(<1% of whole blood)

Erythrocytes(45% of whole blood)

Chapter 17: Blood 6

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 38C, 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

Chapter 17: Blood 7

Functions of Blood

Blood performs a number of functions dealing with:

Substance distribution

Regulation of blood levels of particular substances

Body protection

Chapter 17: Blood 8

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

Chapter 17: Blood 9

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

Chapter 17: Blood 10

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

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:

Give erythrocytes their flexibility

Allow them to change shape as necessary


Erythrocytes (RBCs)

Figure 17.3


Erythrocytes (RBCs)

Erythrocytes are an example of the complementarity of structure and function

Structural characteristics contribute to its gas transport function

Biconcave shape that has a huge surface area relative to volume

Discounting water content, erythrocytes are more than 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 to one oxygen molecule

Each hemoglobin molecule can transport four molecules of oxygen


Structure of Hemoglobin

Figure 17.4


Hemoglobin

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

InterActive Physiology®: Respiratory System: Gas TransportPLAYPLAY


Production of Erythrocytes

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


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


Production of Erythrocytes: Erythropoiesis

Figure 17.5


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

Regulation and Requirements for Erythropoiesis


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


Erythropoietin Mechanism

Figure 17.6

Imbalance

Reduces O2 levels in blood

Erythropoietin stimulates red bone marrow

Enhanced erythropoiesis increases RBC count

Normal blood oxygen levels Stimulus: Hypoxia due to decreased RBC count, decreased availability of O2 to blood, or increased tissue demands for O2

Imbalance

Start

Kidney (and liver to a smaller extent) releases erythropoietin

Increases O2-carrying ability of blood


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

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


Fate and Destruction of Erythrocytes

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 phgocytized


Recycling of Hemoglobin

In macrophages of liver or spleen

globin portion broken down into amino acids & recycled

heme portion split into iron (Fe+3) and biliverdin (green pigment)


Life Cycle of Red Blood Cells

Figure 17.7

Chapter 17: Blood 30Figure 17.7


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

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:

A secondary result of hemorrhagic anemia

Inadequate intake of iron-containing foods

Impaired iron absorption

Pernicious anemia results from:

Deficiency of vitamin B12

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

Erythrocytes are thin, delicate, and deficient in hemoglobin


Severe, chronic anemias (such as thalassemias and sickle cell anemia) can increase the bone marrow response to form RBC's. This drive for erythropoiesis may increase the mass of marrow and lead to increase in marrow in places, such as the skull seen here, that is not normally found. Such an increase in marrow in skull may lead to "frontal bossing" or forehead prominence because of the skull shape change.


Anemia: Abnormal 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


Anemia: Abnormal Hemoglobin


Polycythemia

Polycythemia – excess RBCs that increase blood viscosity

Three main polycythemias are:

Polycythemia vera

Secondary polycythemia

Blood doping


17Blood

(WBC and Homeostasis)


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


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


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 (antihistamines counter this effect)

Basophils


Eosinophils account for 1–4% of WBCs

Have red-staining, bilobed 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

Eosinophils


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 bacteria slayers

Neutrophils


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

Agranulocytes


Account for 25% or more of WBCs and:

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

Are 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

Lymphocytes


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

Monocytes


Macrophages:

Are highly mobile and actively phagocytic

Activate lymphocytes to mount an immune response

Monocytes


Summary of Formed Elements

Table 17.2


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

Interleukins are numbered (e.g., IL-1, IL-2)

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

become myeloblasts or monoblasts

Myeloblasts develop into eosinophils, neutrophils, and basophils

Monoblasts develop into monocytes

lymphoid stem cells

Lymphoid stem cells become lymphoblasts

Lymphoblasts develop into lymphocytes

Formation of Leukocytes


Formation of Leukocytes

Figure 17.11


Leukemia refers to cancerous conditions involving white blood cells

Leukemias are named according to the abnormal white blood cells involved

Myelocytic leukemia – involves myelocytes

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

Figure 17.12


Hematopoiesis


A series of reactions designed for stoppage of bleeding

During hemostasis, three phases occur in rapid sequence

Vascular spasms

Platelet plug formation

Coagulation (blood clotting)

Hemostasis


Vascular Spasm

Immediate vasoconstriction in response to injury


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:

1. With the help of von Willebrand factor (VWF) adhere to collagen

Are stimulated by thromboxane A2

2. Stick to exposed collagen fibers and form a platelet plug

3. 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


Platelet Adhesion

Platelets stick to exposed collagen underlying damaged endothelial cells in vessel wall


Platelet Release Reaction

Platelets activated by adhesion.

Extend projections to make contact with each other.

Release thromboxane A2 & ADP activating other platelets.

Serotonin & thromboxane A2 are vasoconstrictors decreasing blood flow through the injured vessel.


Platelet Aggregation

Activated platelets stick together and activate new platelets to form a mass called a platelet plug.

Plug reinforced by fibrin threads formed during clotting process.


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:

1. Prothrombin activator is formed

2. Prothrombin is converted into thrombin

3. Thrombin catalyzes the joining of fibrinogen into a fibrin mesh

Coagulation


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 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:

Cross-links fibrin

Strengthens and stabilizes the clot

Coagulation Phase 3: Common Pathways to the Fibrin Mesh


Overview of the Clotting Cascade

Prothrombinase is formed by either:

1. intrinsic pathway

2. extrinsic pathway.

Final common pathway produces fibrin threads.


Extrinsic Pathway

Damaged tissues leak tissue factor (thromboplastin) into bloodstream.

In the presence of Ca+2, clotting factor X combines with factor V to form prothrombinase.

Prothrombinase forms in seconds.


Intrinsic Pathway

Activation occurs.

endothelium is damaged & platelets come in contact with collagen of blood vessel wall

platelets damaged & release phospholipids

Substances involved: Ca+2 and clotting factors XII, X and V.

Requires several minutes for reaction to occur.


Final Common Pathway

Prothrombinase and Ca+2

catalyze the conversion of prothrombin to thrombin

Thrombin

in the presence of Ca+2 converts soluble fibrinogen to insoluble fibrin threads

activates fibrin stabilizing factor XIII

positive feedback effects of thrombin

accelerates formation of prothrombinase

activates platelets to release phospholipids


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

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

Swift removal of clotting factors

Inhibition of activated clotting factors

Factors Limiting Clot Growth or Formation


Fibrin acts as an anticoagulant by:

binding thrombin

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

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:

The smooth endothelial lining of blood vessels

Heparin and PGI2 secreted by endothelial cells

Vitamin E quinone, a potent anticoagulant

Factors Preventing Undesirable Clotting


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

Thrombi can block circulation, resulting in tissue death

Coronary thrombosis – thrombus in blood vessel of the heart

Hemostasis Disorders:Thromboembolytic Conditions


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

Hemostasis Disorders:Thromboembolytic Conditions


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

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:

A complication of pregnancy

A result of septicemia or incompatible blood transfusions

Hemostasis 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



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

Blood Transfusions


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 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

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

ABO Blood Groups


ABO Blood Groups

Table 17.4


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:

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

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


Blood Typing

Blood type being tested RBC agglutinogens Serum Reaction

Anti-A Anti-B

AB A and B + +

B B – +

A A + –

O None – –


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

Plasma or plasma expanders can be administered

Plasma Volume Expanders


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 solution can also be used to replace lost blood volume

Plasma Volume Expanders


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

Diagnostic Blood Tests

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