Composition of Blood

• Consists of formed elements (cells) suspended & carried in plasma (fluid part)

• Total blood volume is about 5L

• Plasma is straw-colored liquid consisting of H20 & dissolved solutes– Includes ions, metabolites, hormones, antibodies

13-7

Physical Characteristics of Blood• Average volume of blood:

– 5–6 L for males; 4–5 L for females (Normovolemia)– Hypovolemia - low blood volume– Hypervolemia - high blood volume

• Viscosity (thickness) - 4 - 5 (where water = 1)• The pH of blood is 7.35–7.45; x = 7.4• Salinity = 0.85%

– Reflects the concentration of NaCl in the blood

• Temperature is 38C, slightly higher than “normal” body temperature

• Blood accounts for approximately 8% of body weight

Plasma Proteins

• Constitute 7-9% of plasma• Three types of plasma proteins: albumins, globulins, &

fibrinogen– Albumin accounts for 60-80%

• Creates colloid osmotic pressure that draws H20 from interstitial fluid into capillaries to maintain blood volume & pressure

• Globulins carry lipids– Gamma globulins are antibodies (immunoglobulins)

• Fibrinogen serves as clotting factor– Converted to fibrin – Serum is fluid left when blood clots

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Formed Elements

• Are erythrocytes (RBCs) & leukocytes (WBCs)

• RBCs are flattened biconcave discs– Shape provides increased surface area

for diffusion– Lack nuclei & mitochondria– Each RBC contains 280 million

hemoglobins

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Leukocytes

• Have nucleus, mitochondria, & amoeboid ability

• Can squeeze through capillary walls (diapedesis)– Granular leukocytes help detoxify foreign substances &

release heparin• Include eosinophils, basophils, & neutrophils

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Leukocytes continued

• Agranular leukocytes are phagocytic & produce antibodies

• Include lymphocytes & monocytes

13-11

Platelets (thrombocytes)

• Are smallest of formed elements, lack nucleus

• Are fragments of megakaryocytes • Constitute most of mass of blood

clots• Release serotonin to vasoconstrict &

reduce blood flow to clot area• Secrete growth factors to maintain

integrity of blood vessel wall• Survive 5-9 days

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Components of Whole Blood

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)

• Hematocrit • Males: 47% ± 5%

• Females: 42% ± 5%

Hematopoiesis

• Is formation of blood cells from stem cells in marrow (myeloid tissue) & lymphoid tissue

• Erythropoiesis is formation of RBCs– Stimulated by erythropoietin (EPO) from kidney

• Leukopoiesis is formation of WBCs– Stimulated by variety of cytokines

• = autocrine regulators secreted by immune system

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Life Cycle of Red

Blood Cells

Erythropoiesis

• 2.5 million RBCs are produced/sec

• Lifespan of 120 days• Old RBCs removed

from blood by phagocytic cells in liver, spleen, & bone marrow– Iron recycled back

into hemoglobin production

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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

RBC Antigens & Blood Typing

• Antigens present on RBC surface specify blood type• Major antigen group is ABO system

– Type A blood has only A antigens– Type B has only B antigens– Type AB has both A & B antigens– Type O has neither A or B antigens

13-15

Transfusion Reactions

• People with Type A blood make antibodies to Type B RBCs, but not to Type A

• Type B blood has antibodies to Type A RBCs but not to Type B

• Type AB blood doesn’t have antibodies to A or B

• Type O has antibodies to both Type A & B

• If different blood types are mixed, antibodies will cause mixture to agglutinate

13-16

Transfusion Reactions continued

• If blood types don't match, recipient’s antibodies agglutinate donor’s RBCs

• Type O is “universal donor” because lacks A & B antigens– Recipient’s antibodies won’t

agglutinate donor’s Type O RBCs

• Type AB is “universal recipient” because doesn’t make anti-A or anti-B antibodies– Won’t agglutinate donor’s

RBCs

• Insert fig. 13.6

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• May occur in an Rh- mom pregnanet with an Rh+ fetus• 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

Hemostasis

• Is cessation of bleeding

• Promoted by reactions initiated by vessel injury:– Vasoconstriction restricts blood flow to area– Platelet plug forms

• Plug & surroundings are infiltrated by web of fibrin, forming clot

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Role of Platelets

• Platelets don't stick to intact endothelium because of presence of prostacyclin (PGI2--a prostaglandin) & NO– Keep clots from

forming & are vasodilators

13-20

QuickTime™ and aTIFF (LZW) decompressor

are needed to see this picture.

Role of Platelets

• Damage to endothelium allows platelets to bind to exposed collagen– von Willebrand factor

increases bond by binding to both collagen & platelets

– Platelets stick to collagen & release ADP, serotonin, & thromboxane A2 • = platelet release reaction

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Role of Platelets continued

• Serotonin & thromboxane A2 stimulate vasoconstriction, reducing blood flow to wound

• ADP & thromboxane A2 cause other platelets to become sticky & attach & undergo platelet release reaction– This continues until

platelet plug is formed 13-22

• Platelet plug becomes infiltrated by meshwork of fibrin• Clot now contains platelets, fibrin & trapped RBCs

– Platelet plug undergoes plug contraction to form more compact plug

Role of Fibrin

13-23

• Can occur via 2 pathways:– Intrinsic pathway clots damaged vessels & blood left in test tube

• Initiated by exposure of blood to negatively charged surface of glass or blood vessel collagen– This activates factor XII (a protease) which initiates a series of clotting factors– Ca2+ & phospholipids convert prothrombin to thrombin

» Thrombin converts fibrinogen to fibrin which polymerizes to form a mesh

– Damage outside blood vessels releases tissue thromboplastin that triggers a clotting shortcut (= extrinsic pathway)

Conversion of Fibrinogen to Fibrin

13-24

Fig 13.913-25

Dissolution of Clots

• When damage is repaired, activated factor XII causes activation of kallikrein – Kallikrein converts plasminogen to plasmin

• Plasmin digests fibrin, dissolving clot

13-26

Anticoagulants

• Clotting can be prevented by Ca+2 chelators (e.g. sodium citrate or EDTA)– or heparin which activates antithrombin III (blocks

thrombin)

• Coumarin blocks clotting by inhibiting activation of Vit K– Vit K works indirectly by reducing Ca+2 availability

13-27

Prostaglandins (PGs)

• Are produced in almost every organ

• Belong to eicosanoid family -- all derived from arachidonic acid of plasma membrane

11-72

• Have wide variety of functions– Different PGs may exert antagonistic effects in tissues

• Some promote smooth muscle contraction & some relaxation

• Some promote clotting; some inhibit

– Promotes inflammatory process of immune system– Plays role in ovulation– Inhibits gastric secretion in digestive system

Prostaglandins (PGs) continued

11-73

• Cyclooxygenase (COX) 1 & 2 are involved in PG synthesis – Are targets of a number of inhibitory non-steroidal anti-

inflammatory drugs (NSAIDs)• Aspirin, indomethacin, ibuprofen inhibit both COX 1 & 2 thereby

producing side effects• Celebrex & Vioxx only inhibit COX 2 & thus have few side effects

Prostaglandins (PGs) continued

11-74

• Polycythemia– Abnormal excess of erythrocytes

• Increases viscosity, decreases flow rate of blood

• 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

Anemia: Decreased Hemoglobin Content

Anemia: Abnormal Hemoglobin

• Thalassemias – absent or faulty globin chain in hemoglobin – Erythrocytes are thin, delicate, and deficient in

hemoglobin

• Sickle-cell anemia – results from a defective gene– Codes for an abnormal hemoglobin called hemoglobin

S (HbS)

– This defect causes RBCs to become sickle-shaped in low oxygen situations

Polycythemia

• Polycythemia – excess RBCs that increase blood viscosity

• Three main polycythemias are:– Polycythemia vera– Secondary polycythemia– Blood doping

• Leukemia refers to cancerous conditions involving white blood cells

• Leukemias are named according to the abnormal white blood cells involved– Myelocytic leukemia – involves myeloblasts– 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

• Severe anemia ensues due to excess production of WBC’s

• 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