c hapter 17 blood. b lood c omposition blood: a fluid connective tissue composed of plasma formed...

CHAPTER 17

Blood

BLOOD COMPOSITIONBlood: a fluid connective tissue

composed ofPlasma Formed elements

Erythrocytes (red blood cells, or RBCs)

Leukocytes (white blood cells, or WBCs)

Platelets

BLOOD COMPOSITIONHematocrit

Percent of blood volume that is RBCs

47% ± 5% for males42% ± 5% for femalesConsider 45 % as an average

Copyright © 2010 Pearson Education, Inc. Figure 17.1

1 Withdrawblood and placein tube.

2 Centrifuge theblood sample.

Plasma• 55% of whole blood• Least dense componentBuffy coat• Leukocytes and platelets• <1% of whole bloodErythrocytes• 45% of whole blood• Most dense component

Formedelements

PHYSICAL CHARACTERISTICS AND

VOLUME

Sticky, opaque fluidColor scarlet to dark redpH 7.35–7.4538C~8% of body weightAverage volume: 5 L

FUNCTIONS OF BLOOD

1. Distribution of O2 and nutrients to body

cells Metabolic wastes to the

lungs and kidneys for elimination

Hormones from endocrine organs to target organs

FUNCTIONS OF BLOOD

2. Regulation of Body temperature by

absorbing and distributing heat

Normal pH using buffers

Adequate fluid volume in the circulatory system

FUNCTIONS OF BLOOD3. Protection against

Blood loss Plasma proteins and platelets

initiate clot formation

Infection Antibodies Complement proteins WBCs defend against foreign

invaders

BLOOD PLASMA90% waterProteins are mostly produced by the liver60% albumin36% globulins 4% fibrinogen

BLOOD PLASMANitrogenous by-products of

metabolism—lactic acid, urea, creatinine

Nutrients—glucose, carbohydrates, amino acids

Electrolytes—Na+, K+, Ca2+, Cl–, HCO3

– Respiratory gases—O2 and CO2

Hormones

FORMED ELEMENTSOnly WBCs are complete cellsRBCs have no nuclei or organellesPlatelets are cell fragmentsMost formed elements survive in

the bloodstream for only a few days

Most blood cells originate in bone marrow and do not divide


Platelets

Neutrophils Lymphocyte

Erythrocytes Monocyte

ERYTHROCYTESBiconcave discs, anucleate, essentially no organelles

Filled with hemoglobin (Hb) for gas transportProvide flexibility to change shape as necessary

Are the major factor contributing to blood viscosity


2.5 µm

7.5 µm

Side view (cut)

Top view

ERYTHROCYTES Structural characteristics contribute to

gas transport Biconcave shape—huge surface area

relative to volume>97% hemoglobin (not counting

water)No mitochondria; ATP production is

anaerobic; no O2 is used in generation of ATP

A superb example of complementarity of structure and function!

ERYTHROCYTE FUNCTION

RBCs are dedicated to respiratory gas transport

Hemoglobin binds reversibly with oxygen

ERYTHROCYTE FUNCTION

Hemoglobin structureProtein globin: two alpha and two

beta chainsHeme pigment bonded to each

globin chain Iron atom in each heme can bind to

one O2 molecule Each Hb molecule can transport four

O2


Hemegroup

(a) Hemoglobin consists of globin (two alpha and two beta polypeptide chains) and four heme groups.

(b) Iron-containing heme pigment. Globin chains

Globin chains

HEMOGLOBIN (HB)O2 loading in the lungs

Produces oxyhemoglobin (ruby red)O2 unloading in the tissues

Produces deoxyhemoglobin or reduced hemoglobin (dark red)

CO2 loading in the tissuesProduces carbaminohemoglobin

(carries 20% of CO2 in the blood)

HEMATOPOIESIS

Hematopoiesis (hemopoiesis): blood cell formation Occurs in red bone marrow of

axial skeleton, girdles and proximal epiphyses of humerus and femur

HEMATOPOIESISHemocytoblasts (hematopoietic

stem cells)Give rise to all formed elementsHormones and growth factors

push the cell toward a specific pathway of blood cell development

New blood cells enter blood sinusoids

ERYTHROPOIESIS Erythropoiesis: red blood cell

production A hemocytoblast is

transformed into a proerythroblast

Proerythroblasts develop into early erythroblasts

REGULATION OF ERYTHROPOIESIS

Too few RBCs leads to tissue hypoxia

Too many RBCs increases blood viscosity

Balance between RBC production and destruction depends onHormonal controls Adequate supplies of iron,

amino acids, and B vitamins

HORMONAL CONTROL OF ERYTHROPOIESIS

Erythropoietin (EPO)Direct stimulus for

erythropoiesis Released by the kidneys in

response to hypoxia


Causes of hypoxia Hemorrhage or increased RBC

destruction reduces RBC numbers

Insufficient hemoglobin (e.g., iron deficiency)

Reduced availability of O2 (e.g., high altitudes)


Effects of EPOMore rapid maturation of

committed bone marrow cellsIncreased circulating

reticulocyte count in 1–2 days

Testosterone also enhances EPO production, resulting in higher RBC counts in males

Copyright © 2010 Pearson Education, Inc. Figure 17.6, step 5

Kidney (and liver toa smaller extent)releaseserythropoietin. Erythropoietin

stimulates redbone marrow.

Enhancederythropoiesisincreases RBCcount.

O2- carryingability of bloodincreases.

Homeostasis: Normal blood oxygen levels

Stimulus:Hypoxia (low bloodO2- carrying ability)

due to• Decreased

RBC count• Decreased amount

of hemoglobin• Decreased

availability of O2

1

2

3

4

5

IMBALANCE

IMBALANCE

DIETARY REQUIREMENTS FOR ERYTHROPOIESIS

Nutrients— amino acids, lipids, and carbohydrates

IronStored in Hb (65%), the liver, spleen, and

bone marrowStored in cells as ferritin and hemosiderinTransported loosely bound to the protein

transferrin Vitamin B12 and folic acid —necessary for

DNA synthesis for cell division

FATE AND DESTRUCTION OF ERYTHROCYTES

Life span: 100–120 days

Old RBCs become fragile, and Hb begins to degenerate

Macrophages engulf dying RBCs in the spleen

FATE AND DESTRUCTION OF ERYTHROCYTES

Heme and globin are separatedIron is salvaged for reuseHeme is degraded to yellow the

pigment bilirubinLiver secretes bilirubin (in bile)) into

the intestines Degraded pigment leaves the body

in feces as stercobilin Globin is metabolized into amino

acids


Low O2 levels in blood stimulatekidneys to produce erythropoietin.1


Low O2 levels in blood stimulatekidneys to produce erythropoietin.1

Erythropoietin levels risein blood.2

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

3

New erythrocytesenter bloodstream;function about 120 days.

4


Aged and damaged redblood cells are engulfed bymacrophages of liver,spleen, and bonemarrow; thehemoglobin isbroken down.

5 Hemoglobin

Aminoacids

GlobinHeme

Circulation

Iron storedas ferritin,hemosiderin

Bilirubin

Bilirubin is picked up from bloodby liver, secreted into intestine inbile, metabolized to stercobilin bybacteria, and excreted in feces.


Aged and damaged redblood cells are engulfed bymacrophages of liver,spleen, and bonemarrow; thehemoglobin isbroken down.

5

Raw materials aremade available in bloodfor erythrocyte synthesis.

6

Hemoglobin

Aminoacids

Globin

Iron is bound totransferrin and releasedto blood from liver asneeded for erythropoiesis.

Food nutrients,including amino acids,Fe, B12, and folic acid,are absorbed fromintestine and enterblood.

Heme

Circulation


Bilirubin



Low O2 levels in blood stimulate kidneys to produce erythropoietin.

1

Erythropoietin levels risein blood.2

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

3

Aged and damagedred blood cells areengulfed by macrophagesof liver, spleen, and bonemarrow; the hemoglobinis broken down.

5

New erythrocytesenter bloodstream;function about 120 days.

4

Raw materials aremade available in bloodfor erythrocyte synthesis.

6

Hemoglobin

Aminoacids

Globin

Iron is bound totransferrin and releasedto blood from liver asneeded for erythropoiesis.

Food nutrients,including amino acids,Fe, B12, and folic acid,are absorbed fromintestine and enterblood.

Heme

Circulation


Bilirubin


ERYTHROCYTE DISORDERS

Anemia: blood has abnormally low O2-carrying capacityA sign rather than a disease

itselfBlood O2 levels cannot support

normal metabolismAccompanied by fatigue,

paleness, shortness of breath, and chills

CAUSES OF ANEMIA

1. Insufficient erythrocytes Hemorrhagic anemia: acute

or chronic loss of blood Hemolytic anemia: RBCs

rupture prematurely Aplastic anemia:

destruction or inhibition of red bone marrow

CAUSES OF ANEMIA

2. Low hemoglobin content Iron-deficiency anemia

Secondary result of hemorrhagic anemia or

Inadequate intake of iron-containing foods or

Impaired iron absorption

CAUSES OF ANEMIA

Pernicious anemia ( a hereditory condition)Deficiency of vitamin B12

Lack of intrinsic factor needed for absorption of B12

Treated by intramuscular injection of B12 or application of Nascobal

CAUSES OF ANEMIA

3. Abnormal hemoglobin Thalassemias (a hereditory

condition) Absent or faulty globin

chain RBCs are thin, delicate,

and deficient in hemoglobin

CAUSES OF ANEMIASickle-cell anemia (a hereditory condition)Defective gene codes for abnormal hemoglobin (HbS)

Causes RBCs to become sickle shaped in low-oxygen situations


1 2 3 4 5 6 7 146

1 2 3 4 5 6 7 146

(a) Normal erythrocyte has normal hemoglobin amino acid sequence in the beta chain.

(b) Sickled erythrocyte results from a single amino acid change in the beta chain of hemoglobin.

ERYTHROCYTE DISORDERS

Polycythemia: excess of RBCs that increase blood viscosity

Results from:Polycythemia vera—bone marrow

cancerSecondary polycythemia—when less

O2 is available (high altitude) or when EPO production increases

Blood doping

LEUKOCYTESMake up <1% of total blood volumeCan leave capillaries via diapedesisMove through tissue spaces by

ameboid motion and positive chemotaxis

Leukocytosis: WBC count over 11,000/mm3

Normal response to bacterial or viral invasion


Formedelements

Platelets

Leukocytes

Erythrocytes

DifferentialWBC count(All total 4800 –10,800/l)

Neutrophils (50 – 70%)

Lymphocytes (25 – 45%)

Eosinophils (2 – 4%)

Basophils (0.5 – 1%)

Monocytes (3 – 8%)

Agranulocytes

Granulocytes

GRANULOCYTESGranulocytes: neutrophils, eosinophils, and basophilsCytoplasmic granules stain

specifically with Wright’s stainLarger and shorter-lived than

RBCsLobed nucleiPhagocytic

NEUTROPHILSMost numerous WBCsPolymorphonuclear leukocytes

(PMNs)Fine granules take up both acidic

and basic dyesGive the cytoplasm a lilac colorGranules contain hydrolytic

enzymes or defensins Very phagocytic—“bacteria

slayers”

EOSINOPHILSRed-staining, bilobed nuclei Red to crimson (acidophilic) coarse, lysosome-like granules

Digest parasitic worms that are too large to be phagocytized

Modulators of the immune response

BASOPHILSRarest WBCsLarge, purplish-black (basophilic)

granules contain histamineHistamine: an inflammatory

chemical that acts as a vasodilator and attracts other WBCs to inflamed sites

Are functionally similar to mast cells

Copyright © 2010 Pearson Education, Inc. Figure 17.10 (a-c)

(a) Neutrophil; multilobed nucleus

(b) Eosinophil; bilobed nucleus, red cytoplasmic granules

(c) Basophil; bilobed nucleus, purplish-black cytoplasmic granules

AGRANULOCYTESAgranulocytes: lymphocytes and monocytesLack visible cytoplasmic granules

Have spherical or kidney-shaped nuclei

LYMPHOCYTES

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

Mostly in lymphoid tissue; few circulate in the blood

Crucial to immunity

LYMPHOCYTES

Two types T cells act against virus-infected cells and tumor cells

B cells give rise to plasma cells, which produce antibodies

MONOCYTESThe largest leukocytes

Abundant pale-blue cytoplasm

Dark purple-staining, U- or kidney-shaped nuclei

MONOCYTESLeave circulation, enter tissues,

and differentiate into macrophagesActively phagocytic cells;

crucial against viruses, intracellular bacterial parasites, and chronic infections

Activate lymphocytes to mount an immune response

Copyright © 2010 Pearson Education, Inc. Figure 17.10d, e

(d) Small lymphocyte; large spherical nucleus

(e) Monocyte; kidney-shaped nucleus

LEUKOPOIESISProduction of WBCs

Stimulated by chemical messengers from bone marrow and mature WBCs All leukocytes originate from

hemocytoblasts

LEUKOCYTE DISORDERS Leukopenia

Abnormally low WBC count—drug induced Leukemias

Cancerous conditions involving WBCsNamed according to the abnormal WBC

clone involved Acute leukemia and primarily affects

children Chronic leukemia is more prevalent in older

people

LEUKEMIA Bone marrow totally occupied with

cancerous leukocytes Immature nonfunctional WBCs in the

bloodstream Death caused by internal hemorrhage

and overwhelming infections Treatments include irradiation,

antileukemic drugs, and stem cell transplants

PLATELETS Small fragments of megakaryocytes

Formation is regulated by thrombopoietin

Blue-staining outer region, purple granules

Granules contain serotonin, Ca2+, enzymes, ADP, and platelet-derived growth factor (PDGF)

PLATELETSForm a temporary platelet plug

that helps seal breaks in blood vessels

Circulating platelets are kept inactive and mobile by NO and prostacyclin from endothelial cells of blood vessels


Stem cell Developmental pathway

Hemocyto-blast Megakaryoblast

PromegakaryocyteMegakaryocyte Platelets

HEMOSTASIS Fast series of reactions for

stoppage of bleeding1. Vascular spasm

2. Platelet plug formation (this is not clotting)

3. Coagulation (blood clotting)

VASCULAR SPASM

Vasoconstriction of damaged blood vessel

TriggersDirect injuryChemicals released by

endothelial cells and platelets Pain reflexes

PLATELET PLUG FORMATION

Positive feedback cycleAt site of blood vessel injury, platelets

Stick to exposed collagen fibers with the help of von Willebrand factor, a plasma protein

Swell, become spiked and sticky, and release chemical messengersADP causes more platelets to stick and release their contents

Serotonin and thromboxane A2 enhance vascular spasm and more platelet aggregation


Collagenfibers

Platelets

Fibrin

Step Vascular spasm• Smooth muscle contracts, causing vasoconstriction.

Step Platelet plugformation

• Injury to lining of vessel exposes collagen fibers; platelets adhere.

• Platelets release chemicals that make nearby platelets sticky; platelet plug forms.

Step Coagulation• Fibrin forms a mesh that traps red blood cells and platelets, forming the clot.

1

2

3

COAGULATION A set of reactions in which blood

is transformed from a liquid to a gel

Reinforces the platelet plug with fibrin threads

COAGULATION Three phases of coagulation

1. Prothrombin activator is formed (intrinsic and extrinsic pathways)

2. Prothrombin is converted into thrombin

3. Thrombin catalyzes the joining of fibrinogen to form a fibrin mesh

Copyright © 2010 Pearson Education, Inc. Figure 17.14 (1 of 2)

Vessel endothelium ruptures,exposing underlying tissues(e.g., collagen)

PF3

released byaggregated

platelets

XII

XI

IX

XIIa

Ca2+

Ca2+

XIa

IXa

Intrinsic pathwayPhase 1Tissue cell traumaexposes blood to

Platelets cling and theirsurfaces provide sites formobilization of factors

Extrinsic pathway

Tissue factor (TF)

VII

VIIa

VIII

VIIIa

Ca2+

X

Xa

Prothrombinactivator

PF3

TF/VIIa complexIXa/VIIIa complex

V

Va

Copyright © 2010 Pearson Education, Inc. Figure 17.14 (2 of 2)

Ca2+

Phase 2

Phase 3

Prothrombinactivator

Prothrombin (II)

Thrombin (IIa)

Fibrinogen (I)(soluble)

Fibrin(insolublepolymer) XIII

XIIIa

Cross-linkedfibrin mesh

COAGULATION PHASE 1: TWO PATHWAYS TO PROTHROMBIN

ACTIVATOR

Initiated by either the intrinsic or extrinsic pathway (usually both)Triggered by tissue-damaging eventsInvolves a series of procoagulantsEach pathway cascades toward

factor X

Factor X complexes with Ca2+, PF3, and factor V to form prothrombin activator

COAGULATION PHASE 1: TWO PATHWAYS TO PROTHROMBIN

ACTIVATOR

Intrinsic pathway Is triggered by negatively charged

surfaces (activated platelets, collagen, glass)

Uses factors present within the blood (intrinsic)

Extrinsic pathway Is triggered by exposure to tissue factor

(TF) or factor III (an extrinsic factor)Bypasses several steps of the intrinsic

pathway, so is faster

COAGULATION PHASE 2: PATHWAY TO THROMBIN

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

COAGULATION PHASE 3: COMMON PATHWAY TO THE

FIBRIN MESH

Thrombin converts soluble fibrinogen into fibrin

Fibrin strands form the structural basis of a clot

Fibrin causes plasma to become a gel-like trap for formed elements

Thrombin (with Ca2+) activates factor XIII which:Cross-links fibrinStrengthens and stabilizes the clot

FACTORS PREVENTING UNDESIRABLE CLOTTING

Platelet adhesion is prevented bySmooth endothelial lining of blood

vesselsAntithrombic substances nitric oxide

and prostacyclin secreted by endothelial cells

DISORDERS OF HEMOSTASIS

Thromboembolytic disorders: undesirable clot formation

Bleeding disorders: abnormalities that prevent normal clot formation

THROMBOEMBOLYTIC CONDITIONS

Thrombus: clot that develops and persists in an unbroken blood vesselMay block circulation, leading to tissue

death

Embolus: a thrombus freely floating in the blood streamPulmonary emboli impair the ability of the

body to obtain oxygenCerebral emboli can cause strokes

THROMBOEMBOLYTIC CONDITIONS

Prevented byAspirin

Antiprostaglandin that inhibits thromboxane A2

HeparinAnticoagulant used clinically for pre- and postoperative cardiac care

WarfarinUsed for those prone to atrial fibrillation

BLEEDING DISORDERS Thrombocytopenia: deficient number

of circulating plateletsPetechiae appear due to

spontaneous, widespread hemorrhage

Due to suppression or destruction of bone marrow (e.g., malignancy, radiation)

Platelet count <50,000/mm3 is diagnostic

Treated with transfusion of concentrated platelets

BLEEDING DISORDERS Impaired liver function

Inability to synthesize procoagulants Causes include vitamin K deficiency,

hepatitis, and cirrhosisLiver disease can also prevent the

liver from producing bile, impairing fat and vitamin K absorption

BLEEDING DISORDERS Hemophilias include several similar

hereditary bleeding disorders Hemophilia A: most common type (77% of

all cases); due to a deficiency of factor VIIIHemophilia B: deficiency of factor IXHemophilia C: mild type; deficiency of

factor XI Symptoms include prolonged bleeding,

especially into joint cavities Treated with plasma transfusions and

injection of missing factors

TRANSFUSIONS

Whole-blood transfusions are used when blood loss is substantial

Packed red cells (plasma removed) are used to restore oxygen-carrying capacity

Transfusion of incompatible blood can be fatal

HUMAN BLOOD GROUPS

RBC membranes bear 30 types glycoprotein antigens that arePerceived as foreign if transfused

blood is mismatchedUnique to each individual Promoters of agglutination and are

called agglutinogens Presence or absence of each antigen is

used to classify blood cells into different groups

BLOOD GROUPSHumans have 30 varieties of

naturally occurring RBC antigensAntigens of the ABO and Rh blood

groups cause vigorous transfusion reactions

Other blood groups (MNS, Duffy, Kell, and Lewis) are usually weak agglutinogens

ABO BLOOD GROUPSTypes A, B, AB, and O Based on the presence or absence of

two antigens (agglutinins), A and B on the surface of the RBCs

Blood also contain anti-A or anti-B antibodies (agglutinins) in the plasma that act against transfused RBCs with ABO antigens not normally present

Anti-A or anti-B form in the blood at about 2 months of age

RH BLOOD GROUPS

There are 45 different Rh agglutinogens (Rh factors)

C, D, and E are most common

Rh+ indicates presence of D

RH BLOOD GROUPS

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

Anti-Rh antibodies form if an Rh– individual receives Rh+ blood

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

HOMEOSTATIC IMBALANCE: HEMOLYTIC DISEASE OF THE

NEWBORN

Also called erythroblastosis fetalisRh– mother becomes sensitized

when exposure to Rh+ blood causes her body to synthesize anti-Rh antibodies

Anti-Rh antibodies cross the placenta and destroy the RBCs of an Rh+ baby

HOMEOSTATIC IMBALANCE: HEMOLYTIC DISEASE OF THE

NEWBORN

The baby can be treated with prebirth transfusions and exchange transfusions after birth

RhoGAM serum containing anti-Rh can prevent the Rh– mother from becoming sensitized

TRANSFUSION REACTIONS

Occur if mismatched blood is infused Donor’s cells

Are attacked by the recipient’s plasma agglutinins

Agglutinate and clog small vesselsRupture and release free hemoglobin

into the bloodstream Result in

Diminished oxygen-carrying capacityHemoglobin in kidney tubules and

renal failure

BLOOD TYPINGWhen 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

ABO BLOOD TYPING Blood Type Being Tested

RBC Agglutinogens

Serum Reaction

Anti-A Anti-B

AB A and B + +

B B – +

A A + –

O None – –


SerumAnti-A

RBCs

Anti-B

Type AB (containsagglutinogens A and B;agglutinates with bothsera)

Blood being tested

Type A (containsagglutinogen A;agglutinates with anti-A)

Type B (containsagglutinogen B;agglutinates with anti-B)

Type O (contains noagglutinogens; does notagglutinate with eitherserum)

RESTORING BLOOD VOLUME

Death from shock may result from low blood volume

Volume must be replaced immediately withNormal saline or multiple-electrolyte

solution that mimics plasma electrolyte composition

Plasma expanders (e.g., purified human serum albumin, hetastarch, and dextran) Mimic osmotic properties of albuminMore expensive and may cause significant complications

DIAGNOSTIC BLOOD TESTS

HematocritBlood glucose testsMicroscopic examination reveals variations in size and shape of RBCs, indications of anemias

DIAGNOSTIC BLOOD TESTS

Differential WBC countProthrombin time and platelet counts assess hemostasis

SMAC, a blood chemistry profile

Complete blood count (CBC)

c hapter 17 blood. b lood c omposition blood: a fluid connective tissue composed of plasma formed...

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