Overview of Blood Circulation

Overview of Blood CirculationOverview of Blood Circulation Blood leaves the heart via arteries that branch Blood leaves the heart via arteries that branch

repeatedly until they become capillariesrepeatedly until they become capillaries Oxygen (OOxygen (O22) and nutrients diffuse across ) and nutrients diffuse across

capillary walls and enter tissuescapillary walls and enter tissues Carbon dioxide (COCarbon dioxide (CO22) and wastes move from ) and wastes move from

tissues into the bloodtissues into the blood

Overview of Blood CirculationOverview of Blood Circulation Oxygen-deficient blood leaves the capillaries Oxygen-deficient blood leaves the capillaries

and flows in veins to the heartand flows in veins to the heart This blood flows to the lungs where it releases This blood flows to the lungs where it releases

COCO22 and picks up O and picks up O22 The oxygen-rich blood returns to the heartThe oxygen-rich blood returns to the heart

Composition of BloodComposition of Blood Blood is the body’s only fluid tissueBlood is the body’s only fluid tissue It is composed of liquid plasma and formed It is composed of liquid plasma and formed

elementselements Formed elements include: Formed elements include:

Erythrocytes, or red blood cells (RBCs)Erythrocytes, or red blood cells (RBCs) Leukocytes, or white blood cells (WBCs)Leukocytes, or white blood cells (WBCs) PlateletsPlatelets

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

Components of Whole BloodComponents of Whole Blood

Figure 17.1

Physical Characteristics and Physical Characteristics and VolumeVolume

Blood is a sticky, opaque fluid with a metallic Blood is a sticky, opaque fluid with a metallic tastetaste

Color varies from scarlet to dark redColor varies from scarlet to dark red The pH of blood is 7.35–7.45The pH of blood is 7.35–7.45 Temperature is 38Temperature is 38CC Blood accounts for approximately 8% of body Blood accounts for approximately 8% of body

weightweight Average volume: 5–6 L for males, and 4–5 L for Average volume: 5–6 L for males, and 4–5 L for

femalesfemales

Functions of BloodFunctions of Blood Blood performs a number of functions dealing Blood performs a number of functions dealing

with:with: Substance distributionSubstance distribution Regulation of blood levels of particular substancesRegulation of blood levels of particular substances Body protectionBody protection

DistributionDistribution Blood transports:Blood transports:

Oxygen from the lungs and nutrients from the Oxygen from the lungs and nutrients from the digestive tractdigestive tract

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

Hormones from endocrine glands to target organsHormones from endocrine glands to target organs

RegulationRegulation Blood maintains:Blood maintains:

Appropriate body temperature by absorbing and Appropriate body temperature by absorbing and distributing heatdistributing heat

Normal pH in body tissues using buffer systemsNormal pH in body tissues using buffer systems Adequate fluid volume in the circulatory systemAdequate fluid volume in the circulatory system

ProtectionProtection Blood prevents blood loss by:Blood prevents blood loss by:

Activating plasma proteins and platelets Activating plasma proteins and platelets Initiating clot formation when a vessel is brokenInitiating clot formation when a vessel is broken

Blood prevents infection by: Blood prevents infection by: Synthesizing and utilizing antibodiesSynthesizing and utilizing antibodies Activating complement proteinsActivating complement proteins Activating WBCs to defend the body against Activating WBCs to defend the body against

foreign invaders foreign invaders

Blood PlasmaBlood Plasma Blood plasma contains over 100 solutes, Blood plasma contains over 100 solutes,

including:including: Proteins – albumin, globulins, clotting proteins, Proteins – albumin, globulins, clotting proteins,

and othersand others Lactic acid, urea, creatinineLactic acid, urea, creatinine Organic nutrients – glucose, carbohydrates, amino Organic nutrients – glucose, carbohydrates, amino

acidsacids Electrolytes – sodium, potassium, calcium, Electrolytes – sodium, potassium, calcium,

chloride, bicarbonate chloride, bicarbonate Respiratory gases – oxygen and carbon dioxideRespiratory gases – oxygen and carbon dioxide

Formed ElementsFormed Elements Erythrocytes, leukocytes, and platelets make Erythrocytes, leukocytes, and platelets make

up the formed elementsup the formed elements Only WBCs are complete cellsOnly WBCs are complete cells RBCs have no nuclei or organelles, and platelets RBCs have no nuclei or organelles, and platelets

are just cell fragmentsare just cell fragments Most formed elements survive in the Most formed elements survive in the

bloodstream for only a few daysbloodstream for only a few days Most blood cells do not divide but are renewed Most blood cells do not divide but are renewed

by cells in bone marrowby cells in bone marrow

Components of Whole BloodComponents of Whole Blood

Figure 17.2

Erythrocytes (RBCs)Erythrocytes (RBCs) Biconcave discs, anucleate, essentially no Biconcave discs, anucleate, essentially no

organellesorganelles Filled with hemoglobin (Hb), a protein that Filled with hemoglobin (Hb), a protein that

functions in gas transportfunctions in gas transport Contain the plasma membrane protein spectrin Contain the plasma membrane protein spectrin

and other proteins that:and other proteins that: Give erythrocytes their flexibilityGive erythrocytes their flexibility Allow them to change shape as necessaryAllow them to change shape as necessary

Erythrocytes (RBCs)Erythrocytes (RBCs) Erythrocytes are an example of the Erythrocytes are an example of the

complementarity of structure and functioncomplementarity of structure and function Structural characteristics contribute to its gas Structural characteristics contribute to its gas

transport functiontransport function Biconcave shape has a huge surface area relative to Biconcave shape has a huge surface area relative to

volumevolume Erythrocytes are more than 97% hemoglobinErythrocytes are more than 97% hemoglobin ATP is generated anaerobically, so the erythrocytes ATP is generated anaerobically, so the erythrocytes

do not consume the oxygendo not consume the oxygen they transportthey transport

Erythrocyte FunctionErythrocyte Function RBCs are dedicated to respiratory gas transportRBCs are dedicated to respiratory gas transport Hb reversibly binds with oxygen and most oxygen in Hb reversibly binds with oxygen and most oxygen in

the blood is bound to Hbthe blood is bound to Hb Hb is composed of the protein globin, made up of two Hb is composed of the protein globin, made up of two

alpha and two beta chains, each bound to a heme alpha and two beta chains, each bound to a heme group (an iron atom inside a ring of organic material)group (an iron atom inside a ring of organic material)

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

Each Hb molecule can transport four molecules of Each Hb molecule can transport four molecules of oxygenoxygen

Structure of HemoglobinStructure of Hemoglobin

Figure 17.4

Hemoglobin (Hb)Hemoglobin (Hb) Oxyhemoglobin – Hb bound to oxygenOxyhemoglobin – Hb bound to oxygen

Oxygen loading takes place in the lungsOxygen loading takes place in the lungs Deoxyhemoglobin – Hb after oxygen diffuses Deoxyhemoglobin – Hb after oxygen diffuses

into tissues (reduced Hb) into tissues (reduced Hb) Carbaminohemoglobin – Hb bound to carbon Carbaminohemoglobin – Hb bound to carbon

dioxidedioxide Carbon dioxide loading takes place in the tissues Carbon dioxide loading takes place in the tissues

Production of ErythrocytesProduction of Erythrocytes Hematopoiesis – blood cell formationHematopoiesis – blood cell formation Hematopoiesis occurs in the red bone marrow Hematopoiesis occurs in the red bone marrow

of the:of the: Axial skeleton and girdlesAxial skeleton and girdles Epiphyses of the humerus and femurEpiphyses of the humerus and femur

Hemocytoblasts give rise to all formed Hemocytoblasts give rise to all formed elements elements

Production of Erythrocytes: Production of Erythrocytes: ErythropoiesisErythropoiesis

A hemocytoblast is transformed into a proerythroblastA hemocytoblast is transformed into a proerythroblast Proerythroblasts develop into early erythroblastsProerythroblasts develop into early erythroblasts Ribosome synthesis occurs in early erythroblasts and Ribosome synthesis occurs in early erythroblasts and

mature into late erythroblastsmature into late erythroblasts Hb accumulation in late erythroblasts and Hb accumulation in late erythroblasts and

normoblastsnormoblasts Ejection of the nucleus from normoblasts and Ejection of the nucleus from normoblasts and

formation of reticulocytesformation of reticulocytes Reticulocytes then become mature erythrocytesReticulocytes then become mature erythrocytes

Production of Erythrocytes: Production of Erythrocytes: ErythropoiesisErythropoiesis

Figure 17.5

Regulation and Requirements for Regulation and Requirements for ErythropoiesisErythropoiesis

Circulating erythrocytes – the number remains Circulating erythrocytes – the number remains constant and reflects a balance between RBC constant and reflects a balance between RBC production and destructionproduction and destruction Too few RBCs leads to tissue hypoxiaToo few RBCs leads to tissue hypoxia Too many RBCs causes undesirable blood Too many RBCs causes undesirable blood

viscosityviscosity Erythropoiesis is hormonally controlled and Erythropoiesis is hormonally controlled and

depends on adequate supplies of iron, amino depends on adequate supplies of iron, amino acids, and B vitaminsacids, and B vitamins

Hormonal Control of Hormonal Control of ErythropoiesisErythropoiesis

Erythropoietin (EPO) release by the kidneys is Erythropoietin (EPO) release by the kidneys is triggered by:triggered by: Hypoxia (deficient oxygen) due to decreased Hypoxia (deficient oxygen) due to decreased

RBCsRBCs Decreased oxygen availabilityDecreased oxygen availability Increased tissue demand for oxygen Increased tissue demand for oxygen

Enhanced erythropoiesis increases the: Enhanced erythropoiesis increases the: RBC count in circulating bloodRBC count in circulating blood Oxygen carrying ability of the bloodOxygen carrying ability of the blood

Erythropoiesis requires:Erythropoiesis requires: Proteins, lipids, and carbohydratesProteins, lipids, and carbohydrates Iron, vitamin BIron, vitamin B1212, and folic acid, and folic acid

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

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

Circulating iron is loosely bound to the Circulating iron is loosely bound to the transport protein transferrintransport protein transferrin

Dietary Requirements of Dietary Requirements of ErythropoiesisErythropoiesis

Fate and Destruction of Fate and Destruction of ErythrocytesErythrocytes

The life span of an erythrocyte is 100–120 The life span of an erythrocyte is 100–120 daysdays

Old RBCs become rigid and fragile, and their Old RBCs become rigid and fragile, and their Hb begins to degenerateHb begins to degenerate

Dying RBCs are engulfed by macrophagesDying RBCs are engulfed by macrophages Heme and globin are separated and the iron is Heme and globin are separated and the iron is

salvaged for reusesalvaged for reuse


Heme is degraded to a yellow pigment called Heme is degraded to a yellow pigment called bilirubinbilirubin

The liver secretes bilirubin into the intestines as The liver secretes bilirubin into the intestines as bilebile

The intestines metabolize it into urobilinogen The intestines metabolize it into urobilinogen This degraded pigment leaves the body in feces, This degraded pigment leaves the body in feces,

in a pigment called stercobilinin a pigment called stercobilin


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

Hb released into the blood is captured by Hb released into the blood is captured by haptoglobin and phagocytizedhaptoglobin and phagocytized

Hemoglobin

Aminoacids

Globin

Raw materials aremade available inblood for erythrocytesynthesis.

Iron is bound to transferrin and released to blood from liver as needed for erythropoiesis

Food nutrients,including aminoacids, Fe, B12,and folic acidare absorbedfrom intestineand enter blood

Heme

Circulation

Iron storedas ferritin,hemosiderin

Bilirubin

Bilirubin is picked up fromblood by liver, secreted intointestine in bile, metabolizedto stercobilin by bacteriaand excreted in feces

Erythropoietin levelsrise in blood.

Erythropoietin and necessaryraw materials in blood promoteerythropoiesis in red bone marrow.

New erythrocytesenter bloodstream;function about120 days.

Low O2 levels in blood stimulatekidneys to produce erythropoietin.

Aged and damaged redblood cells are engulfed bymacrophages of liver, spleen,and bone marrow; the hemoglobinis broken down.

1

2

3

4

5

6

Figure 17.7

Anemia – blood has abnormally low oxygen-Anemia – blood has abnormally low oxygen-carrying capacitycarrying capacity It is a symptom rather than a disease itselfIt is a symptom rather than a disease itself Blood oxygen levels cannot support normal Blood oxygen levels cannot support normal

metabolismmetabolism Signs/symptoms include fatigue, paleness, Signs/symptoms include fatigue, paleness,

shortness of breath, and chills shortness of breath, and chills

Erythrocyte DisordersErythrocyte Disorders

Anemia: Insufficient Anemia: Insufficient ErythrocytesErythrocytes

Hemorrhagic anemia – result of acute or Hemorrhagic anemia – result of acute or chronic loss of bloodchronic loss of blood

Hemolytic anemia – prematurely ruptured Hemolytic anemia – prematurely ruptured RBCsRBCs

Aplastic anemia – destruction or inhibition of Aplastic anemia – destruction or inhibition of red bone marrowred bone marrow

Iron-deficiency anemia results from:Iron-deficiency anemia results from: A secondary result of hemorrhagic anemiaA secondary result of hemorrhagic anemia Inadequate intake of iron-containing foodsInadequate intake of iron-containing foods Impaired iron absorptionImpaired iron absorption

Pernicious anemia results from:Pernicious anemia results from: Deficiency of vitamin BDeficiency of vitamin B1212

Lack of intrinsic factor needed for absorption of BLack of intrinsic factor needed for absorption of B1212

Treatment is intramuscular injection of BTreatment is intramuscular injection of B1212; ; application of Nascobalapplication of Nascobal

Anemia: Decreased Hemoglobin Anemia: Decreased Hemoglobin ContentContent

Anemia: Abnormal HemoglobinAnemia: Abnormal Hemoglobin Thalassemias – absent or faulty globin chain in Thalassemias – absent or faulty globin chain in

Hb Hb RBCs are thin, delicate, and deficient in HbRBCs are thin, delicate, and deficient in Hb

Sickle-cell anemia – results from a defective Sickle-cell anemia – results from a defective gene coding for an abnormal Hb called gene coding for an abnormal Hb called hemoglobin S (HbS)hemoglobin S (HbS) HbS has a single amino acid substitution in the beta HbS has a single amino acid substitution in the beta

chainchain This defect causes RBCs to become sickle-shaped This defect causes RBCs to become sickle-shaped

in low oxygen situationsin low oxygen situations

PolycythemiaPolycythemia Polycythemia – excess RBCs that increase Polycythemia – excess RBCs that increase

blood viscosity blood viscosity Three main polycythemias are:Three main polycythemias are:

Polycythemia veraPolycythemia vera Secondary polycythemiaSecondary polycythemia Blood dopingBlood doping

Leukocytes (WBCs)Leukocytes (WBCs) Leukocytes, the only blood components that Leukocytes, the only blood components that

are complete cells:are complete cells: Are less numerous than RBCsAre less numerous than RBCs Make up 1% of the total blood volumeMake up 1% of the total blood volume Can leave capillaries via diapedesisCan leave capillaries via diapedesis Move through tissue spacesMove through tissue spaces

Leukocytosis – WBC count over 11,000 / mmLeukocytosis – WBC count over 11,000 / mm33

Normal response to bacterial or viral invasionNormal response to bacterial or viral invasion

Percentages of LeukocytesPercentages of Leukocytes

Figure 17.9

GranulocytesGranulocytes Granulocytes – neutrophils, eosinophils, and Granulocytes – neutrophils, eosinophils, and

basophilsbasophils Contain cytoplasmic granules that stain Contain cytoplasmic granules that stain

specifically (acidic, basic, or both) with Wright’s specifically (acidic, basic, or both) with Wright’s stainstain

Are larger and usually shorter-lived than RBCsAre larger and usually shorter-lived than RBCs Have lobed nucleiHave lobed nuclei Are all phagocytic cellsAre all phagocytic cells

NeutrophilsNeutrophils Neutrophils have two types of granules that:Neutrophils have two types of granules that:

Take up both acidic and basic dyesTake up both acidic and basic dyes Give the cytoplasm a lilac colorGive the cytoplasm a lilac color Contain peroxidases, hydrolytic enzymes, and Contain peroxidases, hydrolytic enzymes, and

defensins (antibiotic-like proteins)defensins (antibiotic-like proteins) Neutrophils are our body’s bacteria slayersNeutrophils are our body’s bacteria slayers

Eosinophils account for 1–4% of WBCs Eosinophils account for 1–4% of WBCs Have red-staining, bilobed nuclei connected via a Have red-staining, bilobed nuclei connected via a

broad band of nuclear materialbroad band of nuclear material Have red to crimson (acidophilic) large, coarse, Have red to crimson (acidophilic) large, coarse,

lysosome-like granuleslysosome-like granules Lead the body’s counterattack against parasitic Lead the body’s counterattack against parasitic

wormsworms Lessen the severity of allergies by phagocytizing Lessen the severity of allergies by phagocytizing

immune complexes immune complexes

EosinophilsEosinophils

Account for 0.5% of WBCs and:Account for 0.5% of WBCs and: Have U- or S-shaped nuclei with two or three Have U- or S-shaped nuclei with two or three

conspicuous constrictionsconspicuous constrictions Are functionally similar to mast cellsAre functionally similar to mast cells Have large, purplish-black (basophilic) granules Have large, purplish-black (basophilic) granules

that contain histaminethat contain histamine Histamine – inflammatory chemical that acts as a Histamine – inflammatory chemical that acts as a

vasodilator and attracts other WBCs (antihistamines vasodilator and attracts other WBCs (antihistamines counter this effect)counter this effect)

BasophilsBasophils

Agranulocytes – lymphocytes and monocytes:Agranulocytes – lymphocytes and monocytes: Lack visible cytoplasmic granulesLack visible cytoplasmic granules Are similar structurally, but are functionally Are similar structurally, but are functionally

distinct and unrelated cell typesdistinct and unrelated cell types Have spherical (lymphocytes) or kidney-shaped Have spherical (lymphocytes) or kidney-shaped

(monocytes) nuclei(monocytes) nuclei

AgranulocytesAgranulocytes

Account for 25% or more of WBCs and:Account for 25% or more of WBCs and: Have large, dark-purple, circular nuclei with a thin Have large, dark-purple, circular nuclei with a thin

rim of blue cytoplasmrim of blue cytoplasm Are found mostly enmeshed in lymphoid tissue Are found mostly enmeshed in lymphoid tissue

(some circulate in the blood)(some circulate in the blood) There are two types of lymphocytes: T cells There are two types of lymphocytes: T cells

and B cellsand B cells T cells function in the immune responseT cells function in the immune response B cells give rise to plasma cells, which produce B cells give rise to plasma cells, which produce

antibodiesantibodies

LymphocytesLymphocytes

Monocytes account for 4–8% of leukocytes Monocytes account for 4–8% of leukocytes They are the largest leukocytesThey are the largest leukocytes They have abundant pale-blue cytoplasmsThey have abundant pale-blue cytoplasms They have purple-staining, U- or kidney-shaped They have purple-staining, U- or kidney-shaped

nucleinuclei They leave the circulation, enter tissue, and They leave the circulation, enter tissue, and

differentiate into macrophagesdifferentiate into macrophages

MonocytesMonocytes

Macrophages:Macrophages: Are highly mobile and actively phagocyticAre highly mobile and actively phagocytic Activate lymphocytes to mount an immune Activate lymphocytes to mount an immune

responseresponse

MacrophagesMacrophages

LeukocytesLeukocytes

Figure 17.10

Leukopoiesis is stimulated by interleukins and Leukopoiesis is stimulated by interleukins and colony-stimulating factors (CSFs)colony-stimulating factors (CSFs) Interleukins are numbered (e.g., IL-1, IL-2), Interleukins are numbered (e.g., IL-1, IL-2),

whereas CSFs are named for the WBCs they whereas CSFs are named for the WBCs they stimulate (e.g., granulocyte-CSF stimulates stimulate (e.g., granulocyte-CSF stimulates granulocytes)granulocytes)

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

Many hematopoietic hormones are used Many hematopoietic hormones are used clinically to stimulate bone marrow clinically to stimulate bone marrow

Production of LeukocytesProduction of Leukocytes

Formation of LeukocytesFormation of Leukocytes All leukocytes originate from hemocytoblastsAll leukocytes originate from hemocytoblasts Hemocytoblasts differentiate into myeloid stem cells Hemocytoblasts differentiate into myeloid stem cells

and lymphoid stem cellsand lymphoid stem cells Myeloid stem cells become myeloblasts or Myeloid stem cells become myeloblasts or

monoblastsmonoblasts Lymphoid stem cells become lymphoblastsLymphoid stem cells become lymphoblasts Myeloblasts develop into eosinophils, neutrophils, Myeloblasts develop into eosinophils, neutrophils,

and basophilsand basophils Monoblasts develop into monocytes Monoblasts develop into monocytes Lymphoblasts develop into lymphocytesLymphoblasts develop into lymphocytes

(a) (b) (c) (d) (e)

Hemocytoblast

Myeloid stem cell Lymphoid stem cell

Myeloblast MyeloblastMyeloblast Lymphoblast

Stem cells

Committedcells

Promyelocyte PromyelocytePromyelocyte Promonocyte Prolymphocyte

Eosinophilicmyelocyte

Neutrophilicmyelocyte

Basophilicmyelocyte

Eosinophilicband cells

Neutrophilicband cells

Basophilicband cells

Develop-mentalpathway

Eosinophils NeutrophilsBasophils

Granular leukocytes

Plasma cells

Some become

Monocytes Lymphocytes

Macrophages (tissues)

Agranular leukocytesSome become

Figure 17.11

Leukocytes Disorders: LeukemiasLeukocytes Disorders: Leukemias Leukemia refers to cancerous conditions Leukemia refers to cancerous conditions

involving WBCsinvolving WBCs Leukemias are named according to the Leukemias are named according to the

abnormal WBCs involvedabnormal WBCs involved Myelocytic leukemia – involves myeloblastsMyelocytic leukemia – involves myeloblasts Lymphocytic leukemia – involves lymphocytesLymphocytic leukemia – involves lymphocytes

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

Chronic leukemia is more prevalent in older Chronic leukemia is more prevalent in older peoplepeople

LeukemiaLeukemia Immature WBCs are found in the bloodstream in all Immature WBCs are found in the bloodstream in all

leukemiasleukemias Bone marrow becomes totally occupied with cancerous Bone marrow becomes totally occupied with cancerous

leukocytesleukocytes The WBCs produced, though numerous, are not The WBCs produced, though numerous, are not

functionalfunctional Death is caused by internal hemorrhage and Death is caused by internal hemorrhage and

overwhelming infectionsoverwhelming infections Treatments include irradiation, antileukemic drugs, and Treatments include irradiation, antileukemic drugs, and

bone marrow transplantsbone marrow transplants

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

Their granules contain serotonin, CaTheir granules contain serotonin, Ca2+2+, enzymes, , enzymes, ADP, and platelet-derived growth factor (PDGF)ADP, and platelet-derived growth factor (PDGF)

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

Platelets not involved in clotting are kept inactive by Platelets not involved in clotting are kept inactive by NO and prostacyclinNO and prostacyclin

PlateletsPlatelets

Stem cell Developmental pathway

Hemocytoblast Megakaryoblast Promegakaryocyte Megakaryocyte Platelets

Figure 17.12

Genesis of PlateletsGenesis of Platelets The stem cell for platelets is the hemocytoblastThe stem cell for platelets is the hemocytoblast The sequential developmental pathway is as The sequential developmental pathway is as

shown.shown.

HemostasisHemostasis A series of reactions for stoppage of bleedingA series of reactions for stoppage of bleeding During hemostasis, three phases occur in rapid During hemostasis, three phases occur in rapid

sequencesequence Vascular spasms – immediate vasoconstriction in Vascular spasms – immediate vasoconstriction in

response to injuryresponse to injury Platelet plug formationPlatelet plug formation Coagulation (blood clotting)Coagulation (blood clotting)

Platelet Plug FormationPlatelet Plug Formation Platelets do not stick to each other or to blood vesselsPlatelets do not stick to each other or to blood vessels Upon damage to blood vessel endothelium platelets:Upon damage to blood vessel endothelium platelets:

With the help of von Willebrand factor (blood specific With the help of von Willebrand factor (blood specific glycoprotein) adhere to collagenglycoprotein) adhere to collagen

Are stimulated by thromboxane A2 (local hormone-like Are stimulated by thromboxane A2 (local hormone-like chemical; made by kidney)chemical; made by kidney)

Stick to exposed collagen fibers and form a platelet plugStick to exposed collagen fibers and form a platelet plug Release serotonin and ADP, which attract still more Release serotonin and ADP, which attract still more

plateletsplatelets The platelet plug is limited to the immediate area of The platelet plug is limited to the immediate area of

injury by prostacyclin (eicosanoid)injury by prostacyclin (eicosanoid)

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

Coagulation follows intrinsic and extrinsic Coagulation follows intrinsic and extrinsic pathwayspathways

The final three steps of this series of reactions The final three steps of this series of reactions are:are: Prothrombin activator is formedProthrombin activator is formed Prothrombin is converted into thrombinProthrombin is converted into thrombin Thrombin catalyzes the joining of fibrinogen (fibrous-Thrombin catalyzes the joining of fibrinogen (fibrous-

like protein) into a fibrin meshlike protein) into a fibrin mesh

CoagulationCoagulation

CoagulationCoagulation

Figure 17.13a

Detailed Events of CoagulationDetailed Events of Coagulation

Figure 17.13b

Coagulation Phase 1: Two Coagulation Phase 1: Two Pathways to Prothrombin Pathways to Prothrombin

ActivatorActivator May be initiated by either the intrinsic or May be initiated by either the intrinsic or

extrinsic pathwayextrinsic pathway Triggered by tissue-damaging eventsTriggered by tissue-damaging events Involves a series of procoagulantsInvolves a series of procoagulants Each pathway cascades toward factor X (enzyme Each pathway cascades toward factor X (enzyme

essential for coagulation)essential for coagulation) Once factor X has been activated, it combines Once factor X has been activated, it combines

with calcium ions, PFwith calcium ions, PF33, and factor V to form , and factor V to form prothrombin activatorprothrombin activator

Coagulation Phase 2: Pathway to Coagulation Phase 2: Pathway to ThrombinThrombin

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

Coagulation Phase 3: Common Coagulation Phase 3: Common Pathways to the Fibrin MeshPathways to the Fibrin Mesh

Thrombin catalyzes the polymerization (binding of Thrombin catalyzes the polymerization (binding of small molecules to form larger ones) of fibrinogen small molecules to form larger ones) of fibrinogen into fibrininto fibrin

Insoluble fibrin strands form the structural basis of a Insoluble fibrin strands form the structural basis of a clotclot

Fibrin causes plasma to become a gel-like trap Fibrin causes plasma to become a gel-like trap Fibrin in the presence of calcium ions activates factor Fibrin in the presence of calcium ions activates factor

XIII that:XIII that: Cross-links fibrinCross-links fibrin Strengthens and stabilizes the clotStrengthens and stabilizes the clot

Clot Retraction and RepairClot Retraction and Repair Clot retraction – stabilization of the clot by Clot retraction – stabilization of the clot by

squeezing serum from the fibrin strandssqueezing serum from the fibrin strands RepairRepair

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

Fibroblasts form a connective tissue patchFibroblasts form a connective tissue patch Stimulated by vascular endothelial growth factor Stimulated by vascular endothelial growth factor

(VEGF), endothelial cells multiply and restore the (VEGF), endothelial cells multiply and restore the endothelial liningendothelial lining

Factors Limiting Clot Growth or Factors Limiting Clot Growth or FormationFormation

Two homeostatic mechanisms prevent clots Two homeostatic mechanisms prevent clots from becoming largefrom becoming large Swift removal of clotting factors Swift removal of clotting factors Inhibition of activated clotting factorsInhibition of activated clotting factors

Inhibition of Clotting FactorsInhibition of Clotting Factors Fibrin acts as an anticoagulant by binding Fibrin acts as an anticoagulant by binding

thrombin and preventing its:thrombin and preventing its: Positive feedback effects of coagulationPositive feedback effects of coagulation Ability to speed up the production of prothrombin Ability to speed up the production of prothrombin

activator via factor Vactivator via factor V Acceleration of the intrinsic pathway by activating Acceleration of the intrinsic pathway by activating

plateletsplatelets

Inhibition of Clotting FactorsInhibition of Clotting Factors Thrombin not absorbed to fibrin is inactivated Thrombin not absorbed to fibrin is inactivated

by antithrombin IIIby antithrombin III Heparin, another anticoagulant, also inhibits Heparin, another anticoagulant, also inhibits

thrombin activitythrombin activity

Unnecessary clotting is prevented by Unnecessary clotting is prevented by endothelial lining the blood vesselsendothelial lining the blood vessels

Platelet adhesion is prevented by:Platelet adhesion is prevented by: The smooth endothelial lining of blood vesselsThe smooth endothelial lining of blood vessels Heparin and PGIHeparin and PGI22 secreted by endothelial cells secreted by endothelial cells Vitamin E quinone, a potent anticoagulant Vitamin E quinone, a potent anticoagulant

Factors Preventing Undesirable Factors Preventing Undesirable ClottingClotting

Hemostasis Disorders:Hemostasis Disorders:Thromboembolytic ConditionsThromboembolytic Conditions

Thrombus – a clot that develops and persists in Thrombus – a clot that develops and persists in an unbroken blood vesselan unbroken blood vessel Thrombi can block circulation, resulting in tissue Thrombi can block circulation, resulting in tissue

deathdeath Coronary thrombosis – thrombus in blood vessel of Coronary thrombosis – thrombus in blood vessel of

the heartthe heart

Hemostasis Disorders:Hemostasis Disorders:Thromboembolytic ConditionsThromboembolytic Conditions

Embolus – a thrombus freely floating in the Embolus – a thrombus freely floating in the blood streamblood stream Pulmonary emboli can impair the ability of the Pulmonary emboli can impair the ability of the

body to obtain oxygenbody to obtain oxygen Cerebral emboli can cause strokesCerebral emboli can cause strokes

Substances used to prevent undesirable clots:Substances used to prevent undesirable clots: Aspirin – an antiprostaglandin that inhibits Aspirin – an antiprostaglandin that inhibits

thromboxane Athromboxane A22

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

Warfarin – used for those prone to atrial Warfarin – used for those prone to atrial fibrillation fibrillation

Prevention of Undesirable ClotsPrevention of Undesirable Clots

Disseminated Intravascular Coagulation (DIC): Disseminated Intravascular Coagulation (DIC): widespread clotting in intact blood vesselswidespread clotting in intact blood vessels

Residual blood cannot clotResidual blood cannot clot Blockage of blood flow and severe bleeding Blockage of blood flow and severe bleeding

followsfollows Most common as:Most common as:

A complication of pregnancyA complication of pregnancy A result of septicemia or incompatible blood A result of septicemia or incompatible blood

transfusionstransfusions

Hemostasis DisordersHemostasis Disorders

Thrombocytopenia – condition where the Thrombocytopenia – condition where the number of circulating platelets is deficientnumber of circulating platelets is deficient Patients show petechiae due to spontaneous, Patients show petechiae due to spontaneous,

widespread hemorrhage widespread hemorrhage Caused by suppression or destruction of bone Caused by suppression or destruction of bone

marrow (e.g., malignancy, radiation)marrow (e.g., malignancy, radiation) Platelet counts less than 50,000/mmPlatelet counts less than 50,000/mm33 is diagnostic is diagnostic

for this conditionfor this condition Treated with whole blood transfusionsTreated with whole blood transfusions

Hemostasis Disorders: Bleeding Hemostasis Disorders: Bleeding DisordersDisorders

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

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

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

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


Hemophilias – hereditary bleeding disorders Hemophilias – hereditary bleeding disorders caused by lack of clotting factorscaused by lack of clotting factors Hemophilia A – most common type (83% of all Hemophilia A – most common type (83% of all

cases) due to a deficiency of factor VIIIcases) due to a deficiency of factor VIII Hemophilia B – due to a deficiency of factor IXHemophilia B – due to a deficiency of factor IX Hemophilia C – mild type, due to a deficiency of Hemophilia C – mild type, due to a deficiency of

factor XIfactor XI



Symptoms include prolonged bleeding and Symptoms include prolonged bleeding and painful and disabled jointspainful and disabled joints

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

Blood TransfusionsBlood Transfusions Whole blood transfusions are used: Whole blood transfusions are used:

When blood loss is substantial When blood loss is substantial In treating thrombocytopeniaIn treating thrombocytopenia

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

RBC membranes have glycoprotein antigens RBC membranes have glycoprotein antigens on their external surfaceson their external surfaces

These antigens are:These antigens are: Unique to the individual Unique to the individual Recognized as foreign if transfused into another Recognized as foreign if transfused into another

individualindividual Promoters of agglutination and are referred to as Promoters of agglutination and are referred to as

agglutinogens agglutinogens Presence or absence of these antigens is used Presence or absence of these antigens is used

to classify blood groupsto classify blood groups

Human Blood GroupsHuman Blood Groups

Humans have 30 varieties of naturally Humans have 30 varieties of naturally occurring RBC antigensoccurring RBC antigens

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

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

Blood GroupsBlood Groups

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

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

ABO blood groups may have various types of ABO blood groups may have various types of antigens and preformed antibodies antigens and preformed antibodies

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

ABO Blood GroupsABO Blood Groups

ABO Blood GroupsABO Blood Groups

Table 17.4

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

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

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

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

A second exposure to RhA second exposure to Rh++ blood will result in a blood will result in a typical transfusion reactiontypical transfusion reaction

Rh Blood GroupsRh Blood Groups

Hemolytic Disease of the Hemolytic Disease of the NewbornNewborn

Hemolytic disease of the newborn Hemolytic disease of the newborn –– Rh Rh++ antibodies of a sensitized Rhantibodies of a sensitized Rh–– mother cross the mother cross the placenta and attack and destroy the RBCs of placenta and attack and destroy the RBCs of an Rhan Rh++ baby baby

RhRh–– mother becomes sensitized when exposure mother becomes sensitized when exposure to Rhto Rh++ blood causes her body to synthesize Rh blood causes her body to synthesize Rh+ +

antibodiesantibodies

Hemolytic Disease of the Hemolytic Disease of the NewbornNewborn

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

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

Transfusion reactions occur when mismatched Transfusion reactions occur when mismatched blood is infusedblood is infused

Donor’s cells are attacked by the recipient’s Donor’s cells are attacked by the recipient’s plasma agglutinins causing:plasma agglutinins causing: Diminished oxygen-carrying capacityDiminished oxygen-carrying capacity Clumped cells that impede blood flowClumped cells that impede blood flow Ruptured RBCs that release free hemoglobin into Ruptured RBCs that release free hemoglobin into

the bloodstreamthe bloodstream

Transfusion ReactionsTransfusion Reactions

Transfusion ReactionsTransfusion Reactions Circulating hemoglobin precipitates in the Circulating hemoglobin precipitates in the

kidneys and causes renal failurekidneys and causes renal failure

Blood TypingBlood Typing When serum containing anti-A or anti-B When serum containing anti-A or anti-B

agglutinins is added to blood, agglutination agglutinins is added to blood, agglutination will occur between the agglutinin and the will occur between the agglutinin and the corresponding agglutinogenscorresponding agglutinogens

Positive reactions indicate agglutinationPositive reactions indicate agglutination

Blood type being testedBlood type being tested RBC agglutinogensRBC agglutinogens Serum ReactionSerum Reaction

Anti-AAnti-A Anti-BAnti-B

ABAB A and BA and B ++ ++

BB BB –– ++

AA AA ++ ––

OO NoneNone –– ––

Blood TypingBlood Typing

Plasma Volume ExpandersPlasma Volume Expanders When shock is imminent from low blood When shock is imminent from low blood

volume, volume must be replaced volume, volume must be replaced Plasma or plasma expanders can be Plasma or plasma expanders can be

administered administered

Plasma Volume ExpandersPlasma Volume Expanders Plasma expandersPlasma expanders

Have osmotic properties that directly increase fluid Have osmotic properties that directly increase fluid volumevolume

Are used when plasma is not availableAre used when plasma is not available Examples: purified human serum albumin, Examples: purified human serum albumin,

plasminate, and dextran plasminate, and dextran Isotonic saline can also be used to replace lost Isotonic saline can also be used to replace lost

blood volumeblood volume

Diagnostic Blood TestsDiagnostic Blood Tests Laboratory examination of blood can assess an Laboratory examination of blood can assess an

individual’s state of healthindividual’s state of health Microscopic examination:Microscopic examination:

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

Type and number of WBCs – diagnostic of various Type and number of WBCs – diagnostic of various diseasesdiseases

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

Developmental AspectsDevelopmental Aspects Before birth, blood cell formation takes place Before birth, blood cell formation takes place

in the fetal yolk sac, liver, and spleenin the fetal yolk sac, liver, and spleen By the seventh month, red bone marrow is the By the seventh month, red bone marrow is the

primary hematopoietic areaprimary hematopoietic area Blood cells develop from mesenchymal cells Blood cells develop from mesenchymal cells

called blood islandscalled blood islands The fetus forms HbF, which has a higher The fetus forms HbF, which has a higher

affinity for oxygen than adult hemoglobinaffinity for oxygen than adult hemoglobin

Developmental AspectsDevelopmental Aspects Age-related blood problems result from Age-related blood problems result from

disorders of the heart, blood vessels, and the disorders of the heart, blood vessels, and the immune systemimmune system

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

Abnormal thrombus and embolus formation Abnormal thrombus and embolus formation reflects the progress of atherosclerosis reflects the progress of atherosclerosis

Documents

Overview of Blood Circulation