Ch.17 Blood

Front 1

Blood Circulation

Back 1

Starts: Pumping Heart

1. Blood leaves heart through arteries.

2. Diffusion across capillary causes oxygen and nutrients to leave blood & enter body tissues.

3. CO2 & wastes move from the tissues to bloodstream.

4. Oxygen-deficient blood leaves capillaries & flows into viens, which returns it to the heart.

5. The returning blood then flows from heart to lungs where it picks up oxygen.

Ends: Oxygen-rich blood returns to the heart to be pumped throughout the body once again.

Front 2

Composition of Blood

Back 2

1. Blood is the body’s only fluid tissue

2. It is composed of liquid plasma and formed elements

-Formed elements include:
1. Erythrocytes, or red blood cells (RBCs)
2. Leukocytes, or white blood cells (WBCs)
3. Platelets

Front 3

Characteristics & Volume of Blood

Back 3

1. Blood is a sticky, opaque fluid with a metallic taste

2.Color varies from scarlet to dark red

3. The pH of blood is 7.35–7.45

4. Temperature is 38C

5. Accounts for approximately 8% of body weight

6. Average volume:
*5–6 L for males
*4–5 L for females

Front 4

Functions of Blood

Back 4

Blood performs a number of functions dealing with:

1. Substance distribution

2. Regulation of blood levels of particular substances

3. Body protection

Front 5

Functions of Blood:


Distribution

Back 5

Blood transports:

1. Oxygen from the lungs and nutrients from the digestive tract

2. Metabolic wastes from cells to the lungs and kidneys for elimination

3. Hormones from endocrine glands to target organs

Front 6

Function of Blood:


Regulation

Back 6

Blood maintains:

1. Appropriate body temperature by absorbing and distributing heat

2. Normal pH in body tissues using buffer systems

3. Adequate fluid volume in the circulatory system

Front 7

Function of Blood:


Protection

Back 7

1. Blood prevents blood loss by:

-Activating plasma proteins and platelets


-Initiating clot formation when a vessel is broken


2. Blood prevents infection by:

-Synthesizing and utilizing antibodies


-Activating complement proteins


-Activating WBCs to defend the body against foreign invaders

Front 8

Blood Plasma

Back 8

Blood plasma contains over 100 solutes, including:

1. Proteins – albumin, globulins, clotting proteins, and others


2. Lactic acid, urea, creatinine


3. Organic nutrients – glucose, carbohydrates, amino acids


4. Electrolytes – sodium, potassium, calcium, chloride, bicarbonate


5. Respiratory gases – oxygen and carbon dioxide

Front 9

Formed Elements

Back 9

Erythrocytes
Leukocytes
Platelets = the formed elements


1. Only WBCs are complete cells


2. RBCs have no nuclei or organelles, and platelets are just cell fragments


3. Most formed elements survive in the bloodstream for only a few days


4. Most blood cells do not divide but are renewed by cells in bone marrow

Front 10

Erythrocytes (RBCs) Part 1

Back 10

1. Biconcave discs, anucleate, essentially no organelles


2. Filled with hemoglobin (Hb), a protein that functions in gas transport


3. Contain the plasma membrane protein spectrin and other proteins that:

-Give erythrocytes their flexibility


-Allow them to change shape as necessary

Front 11

Erythrocyte (RBCs) Part 2

Back 11

Erythrocytes are an example of the complementarity of structure and function

1. Structural characteristics contribute to its gas transport function


2. Biconcave shape has a huge surface area relative to volume


3. Erythrocytes are more than 97% hemoglobin


4. ATP is generated anaerobically, so the erythrocytes do not consume the oxygen they transport

Front 12

Erythrocyte Function

Back 12

1. RBCs are dedicated to respiratory gas transport


2. Hb reversibly binds with oxygen and most oxygen in the blood is bound to Hb


3. Hb is composed of the protein globin, made up of (2) alpha and (2) beta chains, each bound to a heme group


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


5. Each Hb molecule can transport (4) molecules of oxygen

Front 13

Hemoglobin (Hb)

Back 13

1. Oxyhemoglobin – Hb bound to oxygen

- Oxygen loading takes place in the lungs


2. Deoxyhemoglobin – Hb after oxygen diffuses into tissues (reduced Hb)


3. Carbaminohemoglobin – Hb bound to carbon dioxide

-Carbon dioxide loading takes place in the tissues

Front 14

Production of Erythrocytes

Back 14

1. Hematopoiesis – blood cell formation


2. Hematopoiesis occurs in the red bone marrow of the:
-Axial skeleton and girdles
-Epiphyses of the humerus and femur


3.Hemocytoblasts give rise to all formed elements

Front 15

Production of Erythrocytes: Erythropoiesis

Back 15

1. A hemocytoblast is transformed into a proerythroblast


2. Proerythroblasts develop into early erythroblasts


The developmental pathway consists of three phases

1 – ribosome synthesis in early erythroblasts


2 – Hb accumulation in late erythroblasts and normoblasts



3 – ejection of the nucleus from normoblasts and formation of reticulocytes


-Reticulocytes then become mature erythrocytes

Front 16

Regulation and Requirements for Erythropoiesis

Back 16

1. Circulating erythrocytes – the number stays constant and reflects a balance between RBC production and destruction

-Too few RBCs leads to tissue hypoxia (inadequate oxygen)


-Too many RBCs causes undesirable blood viscosity

2. Erythropoiesis is hormonally controlled and depends on adequate supplies of iron, amino acids, and B vitamins

Front 17

Hormonal Control of Erythropoiesis

Back 17

Erythropoietin (EPO) release by the kidneys is triggered by:

1. Hypoxia due to decreased RBCs

2. Decreased oxygen availability

3. Increased tissue demand for oxygen


Enhanced erythropoiesis increases the:

1. RBC count in circulating blood

2. Oxygen carrying ability of the blood

Front 18

Dietary Requirements of Erythropoiesis

Back 18

Erythropoiesis requires:
- Proteins, lipids, and carbohydrates
- Iron, vitamin B12, and folic acid


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


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


3. Circulating iron is loosely bound to the transport protein transferrin

Front 19

Fate and Destruction of Erythrocytes

Back 19

-lifespan= 100-120 days

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

-Dying RBCs are engulfed by macrophages

-Heme and globin are separated and the iron is salvaged for reuse

Front 20

Fate and Destruction of Erythrocytes (Part 2)

Back 20

-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

Front 21

Erythrocyte Disorders (3)

Back 21

Anemia – blood has abnormally low oxygen-carrying capacity


1. It is a symptom rather than a disease itself


2. Blood oxygen levels cannot support normal metabolism


3. Signs/symptoms include fatigue, paleness, shortness of breath, and chills

Front 22

Anemia: Insufficient Erythrocytes (3)

Back 22

1. Hemorrhagic anemia – result of acute or chronic loss of blood


2. Hemolytic anemia – prematurely ruptured RBCs


3. Aplastic anemia – destruction or inhibition of red bone marrow

Front 23

Anemia: Decreased Hemoglobin Content (2 types)

Back 23

1. Iron-deficiency anemia results from:
- A secondary result of hemorrhagic anemia

- Inadequate intake of iron-containing foods

- Impaired iron absorption


2. 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

Front 24

Anemia: Abnormal Hemoglobin

Back 24

1. Thalassemias – absent or faulty globin chain in Hb

- RBCs are thin, delicate, and deficient in Hb

2. Sickle-cell anemia – results from a defective gene coding for an abnormal Hb 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

Front 25

Polycythemia (3)

Back 25

Polycythemia – excess RBCs that increase blood viscosity

Three main polycythemias are:

1. Polycythemia vera
2. Secondary polycythemia
3. Blood doping

Front 26

Leukocytes (WBCs)

Back 26

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 / mm3

-Normal response to bacterial or viral invasion

Front 27

Granulocytes

Back 27

Granulocytes – neutrophils, eosinophils, and basophils

1. Contain cytoplasmic granules that stain specifically (acidic, basic, or both) with Wright’s stain

2. Are larger and usually shorter-lived than RBCs

3. Have lobed nuclei

4.Are all phagocytic cells

Front 28

Neutrophils

Back 28

Neutrophils have two types of granules that:

1. Take up both acidic and basic dyes

2. Give the cytoplasm a lilac color

3. Contain peroxidases, hydrolytic enzymes, and defensins (antibiotic-like proteins)

4. Neutrophils are our body’s bacteria slayers

Front 29

Eosinophils

Back 29

Eosinophils account for 1–4% of WBCs

1. Have red-staining, bilobed nuclei connected via a broad band of nuclear material

2. Have red to crimson (acidophilic) large, coarse, lysosome-like granules

3. Lead the body’s counterattack against parasitic worms

4. Lessen the severity of allergies by phagocytizing immune complexes

Front 30

Basophils

Back 30

Account for 0.5% of WBCs and:

1. Have U- or S-shaped nuclei with two or three conspicuous constrictions

2. Are functionally similar to mast cells

3. Have large, purplish-black (basophilic) granules that contain histamine

4. Histamine – inflammatory chemical that acts as a vasodilator and attracts other WBCs (antihistamines counter this effect)

Front 31

Agranulocytes

Back 31

Agranulocytes – lymphocytes and monocytes:

1. Lack visible cytoplasmic granules

2. Are similar structurally, but are functionally distinct and unrelated cell types

3. Have spherical (lymphocytes) or kidney-shaped (monocytes) nuclei

Front 32

Lymphocytes

Back 32

1. 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)


2. 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

Front 33

Monocytes

Back 33

Monocytes account for 4–8% of leukocytes

1. They are the largest leukocytes

2. They have abundant pale-blue cytoplasms

3. They have purple-staining, U- or kidney-shaped nuclei

4. They leave the circulation, enter tissue, and differentiate into macrophages

Front 34

Macrophages

Back 34

1. Are highly mobile and actively phagocytic

2. Activate lymphocytes to mount an immune response

Front 35

Production of Leukocytes

Back 35

Leukopoiesis is stimulated by interleukins and colony-stimulating factors (CSFs)

-Interleukins are numbered (e.g., IL-1, IL-2), whereas CSFs are named for the WBCs they stimulate (e.g., granulocyte-CSF stimulates granulocytes)

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

-Many hematopoietic hormones are used clinically to stimulate bone marrow

Front 36

Formation of Leukocytes

Back 36

1. All leukocytes originate from hemocytoblasts

2. Hemocytoblasts differentiate into myeloid stem cells and lymphoid stem cells

3. Myeloid stem cells become myeloblasts or monoblasts

4. Lymphoid stem cells become lymphoblasts

5. Myeloblasts develop into eosinophils, neutrophils, and basophils

6. Monoblasts develop into monocytes

7. Lymphoblasts develop into lymphocytes

Front 37

Leukocytes Disorders: Leukemias

Back 37

Leukemia refers to cancerous conditions involving WBCs

-Leukemias are named according to the abnormal WBCs 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

Front 38

Leukemia

Back 38

1. Immature WBCs are found in the bloodstream in all leukemias

2. Bone marrow becomes totally occupied with cancerous leukocytes

3. The WBCs produced, though numerous, are not functional

4. Death is caused by internal hemorrhage and overwhelming infections

5. Treatments include irradiation, antileukemic drugs, and bone marrow transplants

Front 39

Platelets

Back 39

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

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

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

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

Front 40

Hemostasis

Back 40

1. A series of reactions for stoppage of bleeding

2. During hemostasis, three phases occur in rapid sequence

-Vascular spasms – immediate vasoconstriction in response to injury

-Platelet plug formation

-Coagulation (blood clotting)

Front 41

Platelet Plug Formation

Back 41

1. Platelets do not stick to each other or to blood vessels

2. Upon damage to blood vessel endothelium platelets:
-With the help of von Willebrand factor (VWF) adhere to collagen

-Are stimulated by thromboxane A2

-Stick to exposed collagen fibers and form a platelet plug

-Release serotonin and ADP, which attract still more platelets

-The platelet plug is limited to the immediate area of injury by prostacyclin

Front 42

Coagulation

Back 42

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

Front 43

Coagulation Phase 1: Two Pathways to Prothrombin Activator

Back 43

 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

Front 44

Coagulation Phase 2: Pathway to Thrombin

Back 44

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

Front 45

Coagulation Phase 3: Common Pathways to the Fibrin Mesh

Back 45

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:

1. Cross-links fibrin
2. Strengthens and stabilizes the clot

Front 46

Clot Retraction and Repair

Back 46

 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

Front 47

Factors Limiting Clot Growth or Formation

Back 47

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

Front 48

Inhibition of Clotting Factors

Back 48

Fibrin acts as an anticoagulant by binding thrombin and 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

Front 49

Factors Preventing Undesirable Clotting

Back 49

Unnecessary clotting is prevented by endothelial 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

Front 50

Hemostasis Disorders:
Thromboembolytic Conditions

Back 50

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

2. Coronary thrombosis – thrombus in blood vessel of the heart

3. Embolus – a thrombus freely floating in the blood stream

4. Pulmonary emboli can impair the ability of the body to obtain oxygen

5. Cerebral emboli can cause strokes

Front 51

Prevention of Undesirable Clots

Back 51

Substances used to prevent undesirable clots:

-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

Front 52

Hemostasis Disorders

Back 52

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

Front 53

Hemostasis Disorders: Bleeding Disorders (part2)

Back 53

 Thrombocytopenia – condition where the number of circulating platelets is deficient
 Patients show petechiae 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

Front 54

Hemostasis Disorders: Bleeding Disorders

Back 54

 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

Front 55

Hemostasis Disorders: Bleeding Disorders

Back 55

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 – due to a deficiency of factor IX
 Hemophilia C – mild type, due to 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

Front 56

Blood Transfusions

Back 56

 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

Front 57

Human Blood Groups

Back 57

 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

Front 58

Blood Groups

Back 58

 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

Front 59

ABO Blood Groups

Back 59

 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)
 ABO blood groups may have various types of antigens and preformed antibodies
 Agglutinogens and their corresponding antibodies cannot be mixed without serious hemolytic reactions

Front 60

Rh Blood Groups

Back 60

 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

Front 61

Hemolytic Disease of the Newborn

Back 61

 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 exposure to Rh+ blood causes her body to synthesize 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

Front 62

Transfusion Reactions

Back 62

 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

Front 63

Blood Typing

Back 63

 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

Front 64

Plasma Volume Expanders

Back 64

 When shock is imminent from low blood volume, volume must be replaced
 Plasma or plasma expanders can be administered

 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 can also be used to replace lost blood volume

Front 65

Diagnostic Blood Tests

Back 65

 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

Front 66

Developmental Aspects

Back 66

 Before birth, blood cell formation takes place in the fetal yolk sac, liver, and spleen
 By the seventh month, red bone marrow is the primary hematopoietic area
 Blood cells develop from mesenchymal cells called blood islands
 The fetus forms HbF, which has a higher affinity for oxygen than adult hemoglobin

Front 67

Developmental Aspects (Part2)

Back 67

 Age-related blood problems result from disorders of the heart, blood vessels, and the immune system
 Increased leukemias are thought to be due to the waning deficiency of the immune system
 Abnormal thrombus and embolus formation reflects the progress of atherosclerosis