Chapter 19:

Blood

Primary sources for figures and content:

Marieb, E. N. Human Anatomy & Physiology. 6th ed. San Francisco: Pearson Benjamin Cummings, 2004.

Martini, F. H. Fundamentals of Anatomy & Physiology. 6th ed. San Francisco: Pearson Benjamin Cummings, 2004.

The components of the cardiovascular

system, and their major functions.

The Cardiovascular System

• Cardiovascular system = Anatomical division– A circulating transport system:

• heart• blood vessels• blood

• Circulatory system = Clinical division– Cardiovascular system– Lymphatic system

Functions of the Cardiovascular System

• To transport materials to and from cells:– oxygen and carbon dioxide– nutrients– hormones– immune system components – waste products

The important components and major

functions of blood.

Blood

• Is specialized fluid of connective tissue

• CT = cells in matrix• Functions:

– Distribution– Regulation– Protection

Functions of Blood 1. Distribution

- Deliver oxygen and nutrients to cells- Remove metabolic waste- Transport hormones to targets

2. Regulation- Maintain body temp distribute heat - Maintain pH & fluid volume

3. Protection- Restrict loss at injury (clotting)- Prevent infection (leukocytes)

Characteristics of Blood

1. pH 7.42. Temperature 38⁰C/100.4⁰F3. Total volume 4-6 Liters (9-11 pints)

Estimate your own blood volume:7% body weight in kg = blood in Liters

1kg = 2.2lb (weight lb/2.2) x 0.07 = blood in Liters

Composition of Blood

• Fractionation = Process of separating whole blood into plasma and formed elements

• Blood matrix = Plasma– ~55% (water + soluble proteins)

• Blood cells: formed elements• Erythrocytes: ~45%, transport oxygen• Leukocytes: < 1%, defense• Platelets: < 1%, cell fragments and for clotting

Plasma

• 90% water + dissolved solutes – Nutrients, gasses, hormones, wastes,

ions, proteins

• Plasma Proteins (~8% of total plasma)– 7.6g/100ml of plasma– 5x more proteins than interstitial fluid– Proteins remain in plasma, not absorbed by cells

for nutrients

3 Classes of Plasma Proteins

• Albumins (60%)• Globulins (35%)• Fibrinogen (4%)

Plasma Proteins

1. Albumins (60% of plasma proteins)- Produced by the liver- Functions:

1. Act as pH buffer for blood2. Contribute to osmotic pressure of blood

- Keep water in blood3. Transport fatty acids4. Transport Thyroid hormones5. Transport Steroid hormones

Plasma Proteins

2. Globulins (35% of plasma proteins)1. Gamma globulins / Antibodies /

Immunoglobulins:- Produced by plasma cells in the lymphatic system- Function to attack foreign substances

2. Alpha and Beta globulins/Transport globulins:- Produced by the liver- Function to transport small or insoluble

compounds to prevent filtration loss by the kidney

Plasma Proteins

3. Clotting Factors (4% plasma proteins)- Produced by the liver- 11 total, fibrinogen most abundant- All function to promote or form a clot- Fibrinogen produce long, insoluble

strands of fibrin

**Serum = plasma (-) minus fibrinogen

Plasma Proteins

4. Other (1% of plasma proteins)- From Liver:

- Metabolic enzymes and antibacterial proteins

- From endocrine organs:- Hormones

*Liver disease = leads to blood disorders b/c plasma proteins are produced by the liver

Figure 19–1b

Hemopoiesis

• Process of producing formed elements– Blood cell production

• All formed elements arise from the same progenitor cell– The hemocytoblast, located in the red

bone marrow

KEY CONCEPT

• Total blood volume (liters) = 7% of body weight (kilograms)

• About 1/2 the volume of whole blood is cells and cell products

• Plasma resembles interstitial fluid, but contains a unique mixture of proteins not found in other extracellular fluids

What would be the effects of a decrease in the amount of plasma

proteins?

A. Decrease in plasma osmotic pressure

B. Decrease in ability to fight infection

C. Decrease in transport and binding of some ions, hormones, and other molecules

D. All of the above

Which plasma protein would you expect to be elevated during a viral infection?

A. albumin

B. fibrinogen

C. immunoglobulins

D. regulatory proteins

What are the characteristics and

functions of red blood cells?

Erythrocytes: Red Blood Cells

• 99.9% of blood’s formed elements• 1/3 of total body cells

– Average human = ~75 trillion cells

• Average RBC count = 4.2-6.3 million/µl

Measuring RBCs

• Red blood cell count:– reports the number of RBCs in 1 microliter

whole blood

• Hematocrit (packed cell volume, PCV):– % of whole blood occupied by formed

elements– Mostly erythrocytes: 99.9%– Males have a greater percentage of RBC

then females

Blood Counts

• RBC: Normal Blood Counts– male: 4.5–6.3 million– female: 4–5.5 million

• Polycythemia = excess erythrocytes but normal blood volume– Usually due to bone marrow cancer– hematocrit = viscosity

heart strain and stroke

Erythrocyte Structure

• Small and highly specialized biconcave disc

• Thin in middle and thicker at edge

Figure 19–2d

Importance of RBC Shape and Size

1. Large surface area for gas exchange:– quickly absorbs and releases oxygen

2. Folds and form stacks:– passes through narrow blood vessels

3. Discs bend and flex entering small capillaries:– 7.8 µm diamater passes through

capillary

Erythrocytes

• Mature erythrocytes lack all organelles– Lack nuclei, mitochondria, and ribosomes

• No division, no repair

• Life span < 120 days

• Cell is 97% hemoglobin protein (red color)• Hemoglobin transports oxygen and some

carbon dioxide

The structure and function of hemoglobin.

Hemoglobin Structure• Complex quaternary structure• 2 α chains and 2 β chains• Each chain has one heme group with iron in

center: iron binds oxygen

Figure 19–3

Hemoglobin (Hb)

• Oxyhemoglobin = oxygen bound, RED• Deoxyhemoglobin = no oxygen, BURGUNDY• Fetal Hb binds oxygen stronger than adults

– Insures transfer of oxygen from mom

• Most oxygen is carried in blood bound to Hb, some in plasma

• Only 20% carbon dioxide carried by Hb:– Carbaminohemoglobin – carbon dioxide bound to

amino acids on α / β chains, not on heme

Hemoglobin (Hb) • 280 million Hb/RBC, 4 hemes/Hb, each heme

binds 1 oxygen = >1 billion oxygen/RBC• 25 trillion RBC per person• Normal hemoglobin (adult male):

– 14–18 g/dl whole blood

• When plasma oxygen is low, Hb releases oxygen and binds carbon dioxide

• At lungs carbon dioxide exchanged for oxygen by diffusion

Anemia

• Hemoglobin levels are below normal• Oxygen starvation, due to:

1. Insufficient # RBC’s2. Low Hb3. Abnormal Hb

1. Thalassemia2. Sickle-cell anemia

Abnormal Hb

1. Thalassemia = inability to produce α or β chains

- slow RBC production- cells fragile and short lived

2. Sickle-cell anemia = single amino acid mutation in β chain high oxygen

- cells normal low oxygen- Hb misfolds- RBC’s deform into crescent shape

- RBC’s are fragile, blocks capillaries

Components of old or damaged red blood cells are

recycled.

Figure 19–4

Recycling RBCs

• Macrophages (phagocytes) of liver, spleen, and bone marrow:– monitor RBCs– engulf old/damaged RBCs

• Replaced by new– 1% of circulating RBCs replaced per

day: •about 3 million RBCs per second

Hemoglobin Recycling• Phagocytes break cells down:

1. Protein globulin amino acids, released for use

2.Heme hemoglobin into components:1. Iron is removed:

- It is bound to transferrin in blood for recycling back to bone marrow (new RBCs)

2. Pigment heme to biliverdin (green), Biliverdin bilirubin (yellow-green)- Bilirubin is released into blood- Filtered by liver- Excreted in bile

3. In gut, bilirubin urobilins (yellow),stercobilins (brown)- urobilins is excreted in urine - stercobilins remain in feces

Blood Disorders

• Jaundice– Failure of bilirubin to be excreted in bile,

collects in peripheral tissues– Causes yellow skin and eyes

• Hemoglobinuria:– Cause Hemolysis, RBC rupture in

blood– Red/brown urine due to kidney filtering

intact α and β chains of hemoglobin

How would the hematocrit change after an individual suffered a

hemorrhage?

A. The hematocrit would be higher.

B. The hematocrit would be lower.

C. The hematocrit would show a larger percent WBC.

D. No change would be seen.

How would the level of bilirubin in the blood be affected by a disease that causes damage to the liver?

A. The level would decrease.

B. The level would increase.

C. The level would fluctuate wildly.

D. The level would not change.

Erythropoiesis: The stages of

red blood cell maturation,

and red blood cell production.

Erythropoiesis

• Red blood cell formation • Occurs in reticular CT in red bone

marrow, in spongy bone• Stem cells mature to become RBCs• 2 million/sec (1 oz new blood per

day)

Figure 19–5

RBC Maturation

Hemocytoblasts

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

• become RBCs, some WBCs

– lymphoid stem cells: • become lymphocytes

Erythropoiesis1. Hemocytoblast differentiates into myeloid stem cells2. Followed by many stages of differentiation, all involve an

increase in protein synthesis3. Cell fills with Hb

- loses organelles including the nucleus4. 3-5 days reticulocytes are formed (Hb + some

ribosomes), released into blood.- 1-2% of total blood RBCs

5. 2 days in circulation lose ribosomes = mature erythrocytes

- No more protein synthesis

Components

• Building red blood cells requires:– amino acids– iron

– vitamins B12, B6, and folic acid

•Lack B12 = pernicious anemia–Low RBC production

Stimulating Hormones

• Erythropoietin (EPO) – Also called erythropoiesis-stimulating

hormone:– secreted by the kidney– Secreted when oxygen in tissues is

low (hypoxia = low oxygen level) – due to disease or high altitude– No EPO = Kidney failure b/c low RBCs

Erythropoietin (EPO) • Stimulate RBC production:

– Increase cell division rates (up to 30 million/sec)– Increase Hb synthesis = decrease maturation

time

• “blood doping” = injection EPO or RBC to enhance athletic performance:– Increase oxygen to tissue– Increase hematocrit/viscosity = clots, stroke,

and heart strain

RBC Tests

Table 19–1

KEY CONCEPT

• Red blood cells (RBCs) are the most numerous cells in the body

• RBCs circulate for approximately 4 months before recycling

• Several million are produced each second

• Hemoglobin in RBCs transports: – oxygen from lungs to peripheral tissues– carbon dioxide from tissues to lungs

Blood typing.The basis for ABO

and Rh incompatibilities.

Blood Types

• All cell membranes have surface antigens– Antigens indicate “self”– Antigen = substance that triggers

immune response

• Normal cells are ignored and foreign cells attacked

Blood Types

• Are genetically determined• Classified by the presence or

absence of RBC surface antigens A, B, or D (Rh)

• RBCs have 3 important antigens for transfusion, agglutingens A, B, D (Rh)

Figure 19–6a

4 Basic Blood Types

4 Basic Blood Types

• A (surface antigen A) = 40%• B (surface antigen B) = 10%• AB (antigens A and B) = 4%• O (neither A nor B) = 46%

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

Figure 19–6b

Cross-Reaction

Cross-Reaction• Also called transfusion reaction• At birth, blood contains antibodies against A

or B antigens that are not present• Plasma antibody meets its specific surface

antigen• Antibodies will cause blood agglutination

(clumping) of antigen (agglutinogen) and hemolyze

• If donor and recipient blood types not compatible

Blood Type Test

• Determines blood type and compatibility

Figure 19–7

Cross-Match Test

• Performed on donor and recipient blood for compatibility

• Without cross-match, type O— is universal donor– It lacks all agglutinogens (A, B, and D)

•No risk of agglutination by antibodies in anyone

Erythroblastosis fetalis• Aka Hemolytis disease of the newborn• Antibodies against D antigen only form upon exposure and can

cross the placenta• Rh- mom pregnant with Rh+ baby

– Gets exposed to D antigen during birth– Makes anti-D antibodies– Pregnant with second Rh+ baby– Antibodies cross placenta– Causes agglutination and lysis of fetal RBCs anemia and

death• Prevention = treat mom with RhoCAM during first birth to

prevent antibody formation

What are surface antigens on RBCs?

A. glycoproteins in the cytosol

B. receptor proteins in the cell membrane

C. peripheral proteins of the cell membrane

D. glycolipids in the cell membrane

Which blood type(s) can be transfused into a person with Type O blood?

A. Type A

B. Type B

C. Types A and B

D. Type O

Why can’t a person with Type A blood safely receive blood from a person with

Type B blood?

A. Type B blood will break down in the person’s veins.

B. Type B blood will destroy Type A cells.

C. Type A blood contains agglutinating agents for Type B.

D. Type B blood contains agglutinating agents for Type A.

The types of white blood cells, and

the factors that regulate the production of each

type.

Leukocytes (WBCs) • < 1% of total blood volume

– 6000-9000 leukocytes/µl blood– Use blood to travel to tissues

• Not permanent residents of blood• Most in connective tissue proper and lymphatic system organs

• Function:– Defend against pathogens– Remove toxins and wastes– Attack abnormal/damaged cells

• All have nuclei & organelles, no hemoglobin

Circulating WBCs1. Migrate out of bloodstream (diapedesis)

- Margination = adhere to vessel- Emigration = pass between endothelial cells in vessel

walls

2. Have amoeboid movement in bloodstream3. Attracted to chemical stimuli (positive

chemotaxis)4. Some are phagocytic:

- Engulf pathogens and debris– neutrophils, eosinophils, and monocytes

Figure 19–9

5 Types of WBCs

5 Types of Leukocytes

Granulocytes vs. Agranulocytes (on handout)

1. Neutrophils2. Eosinophils3. Basophils (in tissues = mast cells)4. Monocytes (in tissues = macrophages)5. Lymphocytes

Neutrophils • Also called polymorphonuclear leukocytes (PMNs) • Non-specific defense• Phagocytic• 50–70% of circulating WBCs• 3-5 lobed nucleus• Pale cytoplasm granules with:

– lysosomal enzymes and defensins– bactericides

•hydrogen peroxide and superoxide• Very mobile: first at injury• Life span less than 10 hours

Neutrophil Function

1. Respiratory burst- H2O2 and O2

- , kills and phagocytize

2. Degranulation:- Release defensins (against some bacteria, fungi,

and viruses), lyse bacteria

3. Release prostaglandins- Induce inflammation to stop the spread of injury

4. Release leukotrienes- Attract phagocytes

Degranulation

• Defensins (host defense proteins):– peptides from lysosomes– attack pathogen membranes

Eosinophils

• Also called acidophils• Phagocytic• 2–4% of circulating WBCs• Bilobed nucleus• 12µm diameter• Granules contain toxins• Life span 9 days• Attack large parasites

Eosinophil Functions

1. Phagocytosis of antibody covered objects

2. Defense against parasties:- Exocytose toxins on large pathogens

3. Reduce inflammations- anti-inflammatory chemicals/enzymes

that counteract inflammatory effects of neutorphils and mast cell

BasophilsIn Tissues = Mast cells

• Non-specific defense• Not phagocytic• Are less than 1% of circulating WBCs• Are small, 8-10µm diameter• Granules contain

– Histamine: dilate blood vessels– Heparin: prevents clotting

• Accumulate in damaged tissue• Life span 9 days

Basophil Functions

1. Inflammation (Histamine)

2. Allergic response, also via histamine

MonocytesIn Tissues = Macrophages

• Non-specific defense• Phagocytic• 2–8% of circulating WBCs• Are large and spherical, kidney shaped

nucleus• Circulate 24 hours, exit to tissues =

macrophage• Life span several months

Macrophage Functions

1. Phagocytosis: virus & bacteria2. Attract phagocytes3. Attract fibroblasts for scar

formation4. Activate lymphocytes:

– Mount immune response

Lymphocytes

• Immune response• 20–30% of circulating WBCs• Large round nucleus• 5-17µm diameter, larger than RBCs• Migrate between blood and tissues • Mostly in connective tissues and

lymphatic organs• Life span days to lifetime

3 Classes of Lymphocytes

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

Lymphocyte Functions

1. B cells: - Humoral immunity- Differentiate into plasma cells- Synthesize and secrete antibodies

2. T cells- cell-mediated immunity- attack foreign cells

3. NK cells:- Immune surveillance- Destroy abnormal tissues

KEY CONCEPT

• RBCs outnumber WBCs 1000:1 • WBCs defend against infection,

foreign cells, or toxins• WBCs clean up and repair

damaged tissues

KEY CONCEPT

• The most numerous WBCs: – neutrophils

• engulf bacteria

– lymphocytes• are responsible for specific defenses of

immune response

Which type of white blood cell would you find in the greatest numbers in an infected cut?

A. eosinophils

B. neutrophils

C. lymphocytes

D. monocytes

Which type of cell would you find in elevated numbers in a person who is

producing large amounts of circulating antibodies to combat a virus?

A. B lymphocytes

B. T lymphocytes

C. neutrophils

D. basophils

How do basophils respond during inflammation?

A. secrete antibodies

B. phagocytize foreign particles

C. release histamine

D. reduce inflammation

Figure 19–10

Leukopoiesis:WBC Production

Leukopoiesis• All blood cells originate from hemocytoblasts which produce:

– myeloid stem cells and – lymphoid stem cells

• Lymphoid stem cells Lymphocytes– Production involves the immune response

• Myeloid stem cells Basophils, Eosinophiles, Neutrophils, Macrophages as directed by specific colony stimulating factors (CSF) – CSF is produced by Macrophages and T cells

•Different CSF results in different cell

Myeloid Stem Cells

• Differentiate into progenitor cells:– which produce all WBCs except

lymphocytes

Lymphocytes

• Are produced by lymphoid stem cells

• Lymphopoiesis: – the production of lymphocytes

WBC 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

WBC Disorders• Leukopenia:

– abnormally low WBC count

• Leukocytosis:– abnormally high WBC count in normal blood volume– Normal infection increases WBCs from 7,500 to

11,000/µl• >100,000/µl leukemia, cancerous stem cells

• Leukemia: WBC > 100,000/µl– extremely high WBC count– WBC produced immature and abnormal

Infectious Mononucleosis:

• Epstein Bar virus infection causes:– Production of excess agranulocytes

that are abnormal, self limiting

Table 19–3

The structure and function of platelets

and how are they produced.

Platelets (Thrombocytes)• Cell fragments involved in clotting• Flattened discs, no nucleus• 2-4µm diameter, 1µm thick• Constantly replace

– 9-12 days in circulation– Phagocytosed by cells in spleen

• 350,000/µl blood• 1/3 of total platelets held in reserve in

spleen, mobilized for crisis

Platelet Counts

• 150,000 to 500,000 per microliter • Thrombocytopenia: < 80,000/µl

– abnormally low platelet count– Results in bleeding

• Thrombocytosis: > 1 million/µl– abnormally high platelet count– Due to cancer or infection– Results in a clotting risk

3 Functions of Platelets

1. Transport clotting chemicals, and release important clotting chemicals when activated

2. Temporarily form patch (platelet plug) over damaged vessel walls

3. Actively contract wound after clot formation

- Contain actin and myosin

Platelet Production • Also called thrombocytopoiesis:

– occurs in bone marrow

1. Induced by thrombopoietin from kidney and CSF of leukocytes

2. Megakaryocyte in bone marrow breaks off membrane enclosed cytoplasm to blood

3. Each megakaryocyte can produce ~4,000 platelets

Mechanism that controls blood loss after injury,

and the reaction sequence in blood

clotting.

Hemostasis

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

Figure 19–11a

The Vascular Phase

• A cut triggers vascular spasm • 30-minute contraction

3 Steps of the Vascular Phase

1. Endothelial cells contract: – expose basal lamina to bloodstream

2. Endothelial cells release:– chemical factors:

• ADP, tissue factor, and prostacyclin

– local hormones– stimulate smooth muscle

contraction and cell division

3 Steps of the Vascular Phase

3. Endothelial cell membranes become “sticky”:

– seal off blood flow

The Platelet Phase• Begins within 15 seconds after injury

Figure 19–11b

The Platelet Phase

• Platelet adhesion (attachment):– to sticky endothelial surfaces– to basal laminae– to exposed collagen fibers

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

Activated Platelets Release Clotting Compounds

• Adenosine diphosphate (ADP)

• Thromboxane A2 and serotonin

• Clotting factors• Platelet-derived growth factor

(PDGF) • Calcium ions

The Coagulation Phase

• Begins 30 seconds or more after the injury

Figure 19–12a

The Coagulation Phase

• 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

The Common Pathway

• Enzymes activate Factor X• Forms enzyme prothrombinase• Converts prothrombin to thrombin• Thrombin converts fibrinogen to

fibrin

Functions of Thrombin

• Stimulates formation of tissue factor– forms positive feedback loop

accelerates clotting

KEY CONCEPT

• Platelets are involved in coordination of hemostasis (blood clotting)

• Platelets, activated by abnormal changes in local environment, release clotting factors and other chemicals

• Hemostasis is a complex cascade that builds a fibrous patch that can be remodeled and removed as the damaged area is repaired

A sample of bone marrow has unusually few megakaryocytes.

What body process would you expect to be impaired as a result?

A. hematopoiesis

B. immune response

C. clotting

D. oxygen carrying capacity

Vitamin K is fat-soluble, and some dietary fat is required for its absorption. How could a diet of fruit juice and water have an effect

on blood clotting?

A. Clotting time would increase.

B. Clotting time would decrease.

C. Clotting protein synthesis would increase.

D. Vitamin K has no effect on clotting.

Bleeding Disorders1. Thrombosis

- Clotting in undamaged vessels- Slow or prevent flow

2. Embolus- Free floating thrombosis- Blocks small vessels tissue damage, heart attack,

stroke3. Disseminated intravascular coagulation

- Widespread clotting followed by systemic bleeding- Rare: complication of pregnancy or mismatched

transfusion

Bleeding Disorders

4. Hemophilia:- Inadequate production of clotting

factors- Type A Factor VIII (X linked)- Type B Factor IX- Type C Factor XI

Plasma Clotting Factors

Table 19–4

Blood Disorders5. Dietary:

- Calcium required for clotting cascade- Vitamin K required for liver to synthesize clotting factors- Iron required for hemoglobin production- Vitamin B12 required for RBC stem cell division

6. Organ Health:- Impaired liver =

- reduced clotting b/c of reduced clotting factors- Impaired kidney =

- reduced RBC b/c of reduced EPO- Reduced platelets b/c reduced thrombopoietin

SUMMARY• Functions of cardiovascular system• 5 functions of blood• Structure of whole blood:

– plasma and formed elements• Process of blood cell formation (hemopoiesis)• 3 classes of plasma proteins:

– Albumins, globulins, and fibrinogen• RBC structure and function• Hemoglobin structure and function

SUMMARY• RBC production and recycling• Blood types:

– ABO and Rh• WBC structure and function• 5 types of WBCs:

– Neutrophils, eosinophils, basophils, monocytes, lymphocytes

• Differential WBC counts and disease• WBC production• Platelet structure and function• Platelet production