Ch. 19 BloodThe Cardiovascular System

• A circulating transport system:– a pump (the heart)– a conducting system (blood vessels)– a fluid medium (blood) Functions of the Cardiovascular

System• To transport materials to and from cells:

– oxygen and carbon dioxide– nutrients– hormones– immune system components – waste products

Blood• Is specialized fluid of connective tissue• Contains cells suspended in a fluid matrix

5 Functions of Blood

1. Transport of dissolved substances1. Gases-O2 from lungs to tissues2. Nutrients-from digestive tract, storage, or

liver3. Hormones-such as from endocrine glands to

target cells4. Waste products-from cells to kidneys

2. Regulation of pH and ions

2. Regulation of pH and ionsa. Ions – either add or subtract i.e. Ca

or K by diffusion w/ interstitial fluid & blood

b. Absorbs & neutralize acid- i.e lactic acid from skeletal

muscles3. Restriction of fluid losses at injury sites

- Clotting

4. Defense against toxins and pathogens- WBC – transported by blood to fight infection & remove debris

5. Stabilization of body temperature- Heat loss via skin if hot- Heat retention to brain and other vital organs via shunting

Whole Blood • Plasma:

– Fluid proteins in solution– Like interstitial fluid

• Formed elements: – all cells and cell fragments

Plasma • Water• Dissolved plasma proteins• Other solutes • similar to, & exchanges fluids with, interstitial

fluid• Is matrix of formed elements

3 Types of Formed Elements 1. Red blood cells (RBCs) or erythrocytes:

– transport oxygen

2. White blood cells (WBCs) or leukocytes:– part of the immune system

3. Platelets: cell fragments involved in clotting Hemopoiesis

• Process of producing formed elements• By myeloid and lymphoid stem cells

Fractionation• Process of separating whole blood for

clinical analysis:– into plasma and formed elements

3 General Characteristics of Blood• 38°C (100.4°F) is normal

temperature• High viscosity• Slightly alkaline pH (7.35–7.45)

Blood Volume• Blood volume (liters) = 7% of body

weight (kilograms):– adult male: 5 to 6 liters– adult female: 4 to 5 liters

Figure 19–1b

Plasma• Makes up 50–60% of blood volume• More than 90% of plasma is water

Extracellular Fluids• Interstitial fluid (IF) and plasma• Materials plasma and IF exchange across

capillary walls:– water– ions– small solutes

Differences between Plasma and IF1. Levels of O2 and CO2

2. Dissolved proteins:– plasma proteins do not pass through

capillary walls

3 Classes of Plasma Proteins• Albumins (60%)• Globulins (35%)• Fibrinogen (4%)Albumins • Transport substances:

– fatty acids– thyroid hormones– steroid hormones

Fibrinogen • Molecules form clots • Produce long, insoluble strands of fibrin• If remove clotting proteins, = serum

Globulins 1. Antibodies, also called immunoglobulins

- Attack foreign bodies2. Transport globulins (small molecules):

– hormone-binding proteins – thyroid binding protein binds thyroid hormones; transcortin binds acth (adrenocorticoytropic hormone), stimulates thyroid

– Metalloproteins- i.e. transferrin for Fe– apolipoproteins (lipoproteins)– steroid-binding proteins – i.e. testosterone

binding hormone binds & transports testosterone

Serum• Liquid part of a blood sample in which dissolved

fibrinogen has converted to solid fibrin

Other Plasma Proteins• 1% of plasma:

– changing quantities of specialized plasma proteins

– enzymes, hormones, and prohormones•TSH, FSH, LH, insulin, prolactinOrigins of Plasma Proteins

• 90% made in liver– All albumin and fibrinogen

• Antibodies made by plasma cells made by lymphocytes

• Peptide hormones made by endocrine organs

Red Blood Cells• Red blood cells (RBCs) make up 99.9% of

blood’s formed elementsMeasuring RBCs

• Red blood cell count:– reports # of RBCs in 1 microliter whole blood

• Hematocrit (packed cell volume, PCV):– percentage of RBCs in centrifuged whole

bloodNormal Blood Counts• RBC: male: 4.5–6.3 million, female: 4.–5.5

million• Hematocrit:

– male: 40–54%, female: 37–47%– Why different? Males have androgens

that stimulate RBC production

RBC Structure• Small and highly specialized disc• Thin in middle and thicker at edge

Figure 19–2d

Importance of RBC - Shape and Size

1. High surface-to-volume ratio:– quickly absorbs and releases oxygen

2. Discs form stacks:– smoothes flow through narrow blood vessels

3. Discs bend and flex entering small capillaries:– 7.8 µm RBC passes through 4 µm capillary

Lifespan of RBCs• Lack nuclei, mitochondria, and ribosomes• Live about 120 days

Hemoglobin (Hb) • Protein molecule, transports respiratory

gases• Responsible for cells ability to transport

O2 and CO2• Normal hemoglobin:

– 14–18 g/dl whole blood - males– 12-16 g/dl “” - females

Hemoglobin Structure• Complex

quaternary structure

Figure 19–3

• 4 globular protein subunits:– each with 1 molecule of heme– each heme contains 1 iron ion

• Iron ions easily:– associate with oxygen (oxyhemoglobin) – or dissociate from oxygen (deoxyhemoglobin)

Fetal Hemoglobin• Strong form of hemoglobin found in

embryo/fetus• Takes oxygen from mother’s hemoglobin at the

placenta begins last 7 months in utero and continues over the first year

• FH can be stimulated in adults with SCA or thalassemia – only adult from of hemaglobin is abnormal

Hemoglobin Function• Each RBC has 280 million Hb molecules• Each Hb molecule has 4 heme units

• So each RBC potentially has more 1 billion O2 molecules

Carbaminohemoglobin• With low oxygen (peripheral capillaries):

– hemoglobin releases oxygen which makes plasma CO2 elevated

– Alpha and beta chains binds carbon dioxide and carries it to lungs

– Carbaminohemoglobin is formed– RBC then absorb O2 and releases CO2

Anemia• Hematocrit or hemoglobin levels are

below normal• Is caused by several conditions

Figure 19–4

Recycling RBCs• 1% of circulating

RBCs wear out per day: – about 3 million

RBCs per second

• Macrophages of liver, spleen, and bone marrow:– monitor RBCs– engulf RBCs

before membranes rupture (hemolyze)

Diagnosing Disorders• Hemoglobinuria:

– hemoglobin breakdown products in urine due to excess hemolysis in blood stream

• Hematuria:– whole red blood cells in urine due to kidney

or tissue damageHemoglobin Recycling

• Phagocytes break hemoglobin into components: – globular proteins to amino acids– heme to biliverdin – iron

Iron Recycling• To transport proteins (transferrin) • To storage proteins (feritin and

hemosiderin)Breakdown of Biliverdin• Biliverdin (green) is converted to bilirubin

(yellow)• Bilirubin is:

– excreted by liver (bile)– jaundice is caused by bilirubin buildup– converted by intestinal bacteria to urobilins

and stercobilins

Figure 19–5

RBC MaturationErythropoiesis

• Red blood cell formation • Occurs only in red bone

marrow (myeloid tissue)• Stem cells mature to become

RBCsHemocytoblasts

• Stem cells in bone marrow divide to produce:– myeloid stem cells:

• become RBCs, some WBCs

– lymphoid stem cells: • become lymphocytes

Stages of RBC Maturation• Myeloid stem cell • Proerythroblast• Erythroblasts• Reticulocyte• Mature RBC

Components• Building red blood cells requires:

– amino acids– iron

– vitamins B12, B6, and folic acid

Pernicious Anemia• Low RBC production

• Due to unavailability of vitamin B12

Stimulating Hormones• Erythropoietin (EPO) • Also called erythropoiesis-stimulating

hormone:– secreted when oxygen in peripheral tissues is

low (hypoxia) – due to disease or high altitude

RBC Tests

Table 19–1

Surface Antigens• Are cell surface proteins that identify cells

to immune system – Triggers immune response

• Normal cells are ignored and foreign cells attacked– Each cell has surface AG (antigens)– Allows for recognition of self

Blood Types• Are genetically determined• By presence or absence of RBC surface

antigens A, B, Rh

Figure 19–6a

4 Basic Blood Types

• A (surface antigen A)• B (surface antigen B)• AB (antigens A and B)• O (neither A nor B)

Agglutinogens • Antigens on surface of RBCs• Screened by immune system • Plasma antibodies attack (agglutinate)

foreign antigens Blood Plasma Antibodies

• Type A: type B antibodies• Type B: type A antibodies• Type O: both A and B antibodies• Type AB: neither A nor B

The Rh Factor• Also called D antigen• Either Rh positive (Rh+) or Rh negative (Rh—) • Only sensitized Rh— blood has anti-Rh antibodies• So . . .

– Rh+ mom has Rh- baby - no problems ever– Rh- mom + Rh+ dad = Rh+ baby – no problem for

pregnancy– Blood will mix around delivery & mom will make anti-Rh

AB– Second baby that is Rh+ will be attacked by mom’s anti-

Rh AB can cause death at or before delivery• Known as Hemolytic Disease of the Newborn or erythroblastalis fetalis

• Newborn born with this is anemic and jaundiced• May have to have complete transfusion• RhoGam – to mom prevents production of anti-Rh AB

last 3 months of pregnancy and before and after delivery

Figure 19–6b

Cross-Reaction

• Also called transfusion reaction• Plasma antibody meets its specific

surface antigen• Blood will agglutinate and hemolyze• If donor and recipient blood types not

compatible

White Blood Cells (WBCs) • Also called leukocytes • Do not have hemoglobin• Have nuclei and other organelles

WBC Functions • Defend against pathogens• Remove toxins and wastes• Attack abnormal cells

WBC Movement• Most WBCs in connective tissue proper &

lymphatic system organs • Small numbers in blood: 6000 to 9000

per microliter

Circulating WBCs1. Migrate out of bloodstream

- Margination-activated WBCs adhere to vessel walls, then can squeeze thru (emigration or diapedesis)

2. Have amoeboid movement- Gliding movement, needs ATP and Ca- Movement of emigration

3. Attracted to chemical stimuli (positive chemotaxis)

- Chemicals guide WBC to invading pathogens, damaged tissues, and other WBC

4. Some are phagocytic:– neutrophils, eosinophils (microphages), and

monocytes (macrophage)– Engulf waste and pathogens

Figure 19–9

Types of WBCs

• Neutrophils• Eosinophils• Basophils• Monocytes• Lymphocytes

Neutrophils • Also called polymorphonuclear leukocytes • 50–70% of circulating WBCs• 12 um in dia• 10 hour life span - eats 12-24 bacteria first• Very dense 2-5 segment nucleus• Pale cytoplasm granules with lysosomal enzymes &

bactericides (hydrogen peroxide and superoxide)

Neutrophil Action • Very active, first to attack bacteria, fungi, and some

viruses• Engulf pathogens• Digest pathogens• Release prostaglandins (hormones) and leukotrienes

(calls other cells). Contributes to local inflammation• Form pus (dead neutrophils, cell debris and waste)

Eosinophils • Also called acidophils• 2–4% of circulating WBCs• 12 um dia• 2 lobed nucleus• Attack large parasites, then toxic

compounds: nitric oxide & cytotoxic enzymesEosinophil Actions

• Are sensitive to allergens • Control inflammation with enzymes that

counteract inflammatory effects of neutrophils and mast cells

Basophils • Are less than 1% of circulating

WBCs• Are small - <8-10 um diameter• Migrate to site via capallaries• Accumulate in damaged tissueBasophil Actions• Release chemicals that attract basophils and

eosinophils• Granuales discharged into interstitial fluid.

They contain:• histamine:

– dilates blood vessels

• heparin:– prevents blood clotting Both enhance inflammation

Monocytes • += 15 um diam• 2–8% of circulating WBCs• Are large and spherical• Large or kidney nucleus• Enter peripheral tissues and become

macrophages after 24 hours – aggressive

Macrophage Actions• Engulf large particles and pathogens• Secrete substances that attract immune

system cells and fibroblasts to injured area

Lymphocytes• 20–30% of circulating WBCs• Very small, but larger than RBCs• Large round nucleus w/ thin cytopalmic halo• Migrate in and out of blood• Mostly in connective tissues & lymphatic

organs Lymphocyte Actions • Are part of the body’s specific defense

system• 3 classes1. T cells

2. B cells 3. Natural killer (NK) cells

T cells • Cell-mediated immunity• Attack foreign cells directly• Coordinates immune response

B cells • Humoral immunity

– Produce and distribute AB

• Differentiate into plasma cells– Synthesize and distribute antibodies

Natural Killer Cells (NK) • Immune survelliance• Detect and destroy abnormal tissue cells

(cancers)

WBC Disorders• Leukopenia: abnormally low WBC count• Leukocytosis: abnormally high WBC

count• Leukemia: extremely high WBC countWBC Production

• All blood cells originate from hemocytoblasts:– which produce

myeloid stem cells and lymphoid stem cells

Myeloid Stem Cells • Differentiate into progenitor cells:

– which produce all WBCs except lymphocytesLymphocytes

• Are produced by lymphoid stem cells• Lymphopoiesis: the production of

lymphocytesWBC Development• WBCs, except monocytes: develop fully in

bone marrow• Monocytes: develop into macrophages in

peripheral tissues

Other Lymphopoiesis• Some lymphoid stem cells migrate to

peripheral lymphoid tissues (thymus, spleen, lymph nodes)

• Also produce lymphocytes

Summary: Formed Elements of Blood

Table 19–3

Platelets• Cell fragments involved in human clotting

system - 4um dia and 1 um thick – “sticky”• Nonmammalian vertebrates have thrombocytes

(nucleated cells)

Platelet Circulation• Circulates for 9–12 days• Dead removed by phagocytosis in spleen• 2/3 are reserved for emergencies

Platelet Counts• 150,000 to 500,000 per microliter • Thrombocytopenia: abnormally low platelet

count• Thrombocytosis: abnormally high platelet

count

3 Functions of Platelets1. Release important clotting chemicals2. Temporarily patch damaged vessel walls3. Actively contract tissue after clot

formationPlatelet Production • Also called thrombocytopoiesis: occurs in

bone marrowMegakaryocytes• Giant cells• Manufacture platelets from cytoplasm• Each cell produces ~4000 platelets

Hemostasis

• The cessation of bleeding:– vascular phase– platelet phase– coagulation phase

1. Endothelial cells contract

2. Contraction is due to 1. Endothelial cells and platelets releasing chemicals2. pain receptors initiate reflexes

– stimulate smooth muscle contraction 3. Endothelial cell membranes become “sticky”: - seal off blood flowVon Willebrand factor (large plasma protein) synthesized by

endothelial cells causes the stickiness by binding to proteins and cells

The Vascular Phase• A cut triggers immediate response = vascular

spasm • 20 to 30-minute contraction

The Platelet Phase• Begins within 15 seconds after injury

Figure 19–11b

• Platelet adhesion (attachment):– to sticky

endothelial surfaces

– to basal laminae– to exposed

collagen fibers

• Platelet aggregation (stick together):– forms platelet plug which closes small

breaks

Activated Platelets Release Clotting Compounds

• Granules in Platelets break down and release– Adenosine diphosphate (ADP) – aggregating

agent (more platelets)

– Thromboxane A2 and serotonin – enhance vascular spasm

This is a positive feedback cycle that activates and attracts more and more platelets to the area.

Within 1 minute a platelet plug is built

Platelet Plug: Size Restriction

• Prostacyclin:– released by endothelial cells– inhibits platelet aggregation

• Inhibitory compounds:– released by other white blood cells

The Coagulation Phase• Begins 30 seconds or more after the

injury

Figure 19–12a

• Blood clotting (coagulation):– Involves a series of

steps – converts circulating

fibrinogen into insoluble fibrin

• Blood Clot– Fibrin network– Covers platelet

plug– Traps blood cells– Seals off area

• Clotting factors– Also called procoagulants – Proteins or ions in plasma– Required for normal clotting

Cascade Reactions• During coagulation phase • Chain reactions of enzymes and proenzymes• Form 3 pathways

3 Coagulation Pathways• Extrinsic pathway:

– begins in the vessel wall– outside blood stream

• Intrinsic pathway:– begins with circulating proenzymes– within bloodstream

• Common pathway:– where intrinsic and extrinsic pathways

converge

3 Coagulation Pathways

The Extrinsic Pathway • Damaged cells release tissue factor (TF) • TF + other compounds = enzyme

complex• Activates Factor X

The Intrinsic Pathway • Activation of enzymes by collagen • Platelets release factors (e.g., PF–3) • Series of reactions activate Factor X

The Common Pathway • Enzymes activate Factor X• Forms enzyme prothrombinase• Converts prothrombin to thrombin• Thrombin converts fibrinogen to fibrin

– Thrombin stimulates formation of tissue factor• stimulates release of PF-3:• forms positive feedback loop (intrinsic and

extrinsic):– accelerates clotting

Clotting: Area Restriction1. Anticoagulants (plasma proteins): antithrombin-III

& alpha-2-macroglobulin2. Heparin 3. Protein C (activated by thrombomodulin)4. Prostacyclin

Other Factors• Calcium ions (Ca2+) and vitamin K are

both essential to the clotting processClot Retraction

• After clot has formed:– Platelets contract and pull torn area together

• Takes 30–60 minutes Fibrinolysis

• Slow process of dissolving clot:– thrombin and tissue plasminogen activator (t-

PA): activate plasminogen

• Plasminogen produces plasmin: digests fibrin strands

Disorders of Hemostasis• Thrombembolic disorders – clots too easily

– Thrombus – clot that develops and persists in an unbroken blood vessel (may prevent blood flow and cause tissue death) - Coronary thrombosis

– Embolus – thrombus that breaks away from the vessel wall and travels through bloodstream

– Embolism – obstructs a vessel (pulmonary embolism)– Bedridden patients, long flights (slow moving blood)

• Bleeding Disorders – prevent normal clotting– Thrombocytopenia – platelet numbers low– Impaired liver function – not able to synthesize coagulants– Hemophilias – several hereditary conditions (person doesn’t make the

clotting factors correctly