Chapter 11: Hematology (Blood)

BLOOD

Functions of Blood

Blood helps maintain homeostasis in several ways:

1. Transport of gases, nutrients, waste products

2. Transport of processed molecules

3. Transport of regulatory molecules

4. Regulation of pH and osmosis

5. Maintenance of body temperature

6. Protects against foreign substances such as microorganisms and

toxins

7. Blood clotting prevents fluid and cell loss and is part of tissue repair

Composition of Blood
· Blood is a connective tissue consisting of plasma and formed elements

· Blood is the body’s only fluid tissue

· 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

· Hematocrit: the percentage of RBCs out of the total blood volume

· Total blood volume is approximately 5 liters

· Blood is a sticky, opaque fluid with a metallic taste

· Color varies from scarlet to dark red

· The pH of blood is 7.35–7.45

· Temperature is 38°C

· Blood accounts for approximately 8% of body weight

· Average volume: 5–6 L (1.5 gallons) for males, and 4–5 L for female

Plasma

· Pale yellow fluid containing over 100 solutes

· Mostly water (91%)

· Contains proteins (7%)

o Albumin (58% of the plasma proteins)

§ Helps maintain osmotic pressure

o Globulins (38% of the plasma proteins)

o Immunity: antibodies and complement

o Transport: bind to molecules such as hormones

· Clotting Factors

o Fibrinogen (4% of the plasma proteins)

o Converted to fibrin during clot formation

· Other substances (2%)

o Ions (electrolytes): sodium, potassium, calcium, chloride, bicarbonate

o Nutrients: glucose, carbohydrates, amino acids

o Waste products: lactic acid, urea, creatinine

o Respiratory gases: oxygen and carbon dioxide

Formed Elements

1. Erythrocytes or red blood cells (RBCs)

o About 95% of formed elements

o RBCs have no nuclei or organelles

2. Leukocytes or white blood cells (WBCs)

· Most of the remaining 5% of formed elements

· Only WBCs are complete cells

· Five types of WBCs

3. Platelets

· Just cell fragments

Most formed elements survive in the bloodstream for only a few days
Production of Formed Elements

Most blood cells do not divide but are renewed by stem cells
(hemocytoblasts) in bone marrow
Hematopoiesis: blood cell production

· Occurs in different locations before and after birth

o Fetus

o Liver, thymus, spleen, lymph nodes, and red bone marrow

o After birth

o In the red bone marrow of the

o Axial skeleton and girdles

o Epiphyses of the humerus and femur

o Some white blood cells are produced in lymphatic tissues

· Hemocytoblasts give rise to all formed elements

· Growth factors determine the type of formed element derived from the
stem cell

Red Blood Cells

· Biconcave discs, anucleated, essentially no organelles

· RBCs are dedicated to respiratory gas transport

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

· RBCs are an example of how structure fits function

· Biconcave shape has a huge surface area relative to volume

· Structural characteristics contribute to its gas transport function

· Biconcave shape also allows RBCs to bend or fold around their thin
center

Hemoglobin (Hb)

· Accounts for about a third of the cell’s volume

· Consists of:

1. The protein globin, made up of two alpha and two beta chains, each
bound to a heme group
2. Each heme group bears an atom of iron, which can bind to one
oxygen molecule

3. Heme molecules transport oxygen (Iron is required)

· Oxygen content determines blood color

o Oxygenated: bright red

o Deoxygenated: darker red

2. Globin molecules transport carbon dioxide

3. One RBC contains 250 million Hb groups thus it can carry 1 billion
molecules of O2

4. Transport of Oxygen and Carbon Dioxide

Oxygen

· Transported bound to hemoglobin ~98.5%

· Dissolved in plasma ~1.5%

· Each Hb molecule binds four oxygen atoms in a rapid and reversible

process

Carbon dioxide

· Dissolved in plasma ~7%

· Transported as bicarbonate(HCO3–) ~70%

· Chemically bound to hemoglobin ~23%

Transport and Exchange of Carbon Dioxide

· Carbon dioxide diffuses into RBCs and combines with water to form
carbonic acid (H2CO3), which quickly dissociates into hydrogen ions and
bicarbonate ions

· In RBCs, carbonic anhydrase reversibly catalyzes the conversion of carbon

dioxide and water to carbonic acid
Erythropoiesis is the production of RBCs

· A hemocytoblast is transformed into a proerythroblast

· Proerythroblasts develop into early erythroblasts

· The developmental pathway consists of three phases

1. Ribosome synthesis in early erythroblasts

2. Hb accumulation in intermediate erythroblasts and late erythroblasts

3. Ejection of the nucleus from late erythroblasts and formation of

reticulocytes

· Reticulocytes are released from the red bone marrow into the
circulating blood, which contains ~1-3% reticulocytes

4. Reticulocytes then become mature erythrocytes

Red Blood Cell Production

1. Circulating erythrocytes: The number remains constant and reflects a

balance between RBC production and destruction

a. Too few RBCs leads to tissue hypoxia

b. Too many RBCs causes undesirable blood

2. Erythropoiesis is hormonally controlled and depends on adequate supplies
of iron, amino acids, and B vitamins (folate and B12)

1. Erythropoietin (EPO) release by the kidneys is triggered by

a. Hypoxia due to decreased RBCs

b. Decreased oxygen availability

c. Increased tissue demand for oxygen

2. Enhanced erythropoiesis increases the

a. RBC count in circulating blood

b. Oxygen carrying ability of the blood

Hemolysis- breaking down of red blood cells

1. The life span of an erythrocyte is 100–120 days

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

3. Dying RBCs are engulfed by macrophages located in the spleen or liver

4. Heme and globin are separated and the iron is salvaged for reuse

a. Globin chains are broken down to individual amino acids and are
metabolized or used to build new proteins

b. Iron released from heme is transported to the red bone marrow and is
used to produce new hemoglobin

c. Heme becomes bilirubin that is secreted in bile

1. In the intestines bilirubin is converted by bacteria into other

pigments
 a. Gives feces its brown color

b. Gives urine its yellow color

White Blood Cells

· Only blood components that are complete cells

· Are less numerous than RBCs

· Make up 1% of the total blood volume

· Can leave capillaries via ameboid movement and move through tissue
spaces

· Two functions of WBCs

· Protect the body against invading microorganisms

· Remove dead cells and debris from tissues by phagocytosis

· Named according to their appearance in stained preparations

· Granulocytes: contain large cytoplasmic granules

· Agranulocytes: very small granules that cannot be easily seen with

the light microscope

Granulocytes: neutrophils, eosinophils, and basophils

· Contain cytoplasmic granules that stain specifically (acidic, basic, or

both) with Wright’s stain

· Are larger and usually shorter-lived than RBCs

· Have lobed nuclei

· Are all phagocytic cells

1. Neutrophils most common type of WBC

· Have two types of granules that:

a. Take up both acidic and basic dyes

b. Give the cytoplasm a lilac color

c. Contain peroxidases, hydrolytic enzymes, and defensins

(antibiotic-like proteins)

· Neutrophils are our body’s bacteria slayers

· Pus is an accumulation of dead neutrophils, cell debris and fluid at

sites of infections
2. Basophils account for 0.5% of WBCs

· Have large, purplish-black (basophilic) granules that contain

· Histamine: inflammatory chemical that acts as a vasodilator and

attracts other WBCs (antihistamines counter this effect)

· Heparin: prevents the formation of clots

3. Eosinophils

· Have red-staining, bilobed nuclei connected via a broad band of

nuclear material

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

· Lessen the severity of allergies by reducing inflammation

· Lead the body’s counterattack against parasitic worms

Agranulocytes: lymphocytes and monocytes

· Lack visible cytoplasmic granules

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

· Have spherical (lymphocytes) or kidney-shaped (monocytes)

nuclei

1. Lymphocytes account for 25% or more of WBCs

· 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)

· There are two types of lymphocytes: T cells and B cells

1. B cells

· Stimulated by bacteria or toxins

· Give rise to plasma cells, which produce antibodies

2. T cells

· Protect against viruses and other intracellular microorganisms

· Attack and destroy the cells that are infected

2. Monocytes account for 4–8% of leukocytes

· They are the largest leukocytes

· They have an abundant pale-blue cytoplasm

· They have purple-staining, U- or kidney-shaped nuclei

· They leave the circulation, enter tissue, and differentiate into

macrophages

· Are highly mobile and actively phagocytic

· Activate lymphocytes to mount an immune response

Platelets

 Fragments of megakaryocytes with a blue-staining outer region and a

purple granular center
 Function in clotting by two mechanisms

– Formation of platelet plugs, which seal holes in small vessels

– Formation of clots, which help seal off larger wounds in the vessels

 Their granules contain ADP and thromboxanes

Preventing Blood Loss

· A series of reactions for stoppage of bleeding

Three phases occur in rapid sequence:

· Vascular spasms

– immediate vasoconstriction in response to injury

• Thromboxanes and endothelin can cause vascular spasms

– Platelet plug formation

– Coagulation (blood clotting)

. Platelet Plugs

– Platelets do not stick to each other or to blood vessels

– Upon damage to blood vessel endothelium platelets:

• With the help of von Willebrand factor (VWF) adhere to collagen

• Are stimulated by and then release more thromboxane and ADP,

which attract still more platelets

• Stick to exposed collagen fibers and form a platelet plug

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

prostacyclin

– Can seal up a small breaks in a blood vessels that occur many times
each day

. Blood clotting

– or coagulation, is the formation of a clot (a network of protein fibers

called fibrin)

– Blood clotting begins with the extrinsic or intrinsic pathway

– Both pathways end with the production of activated factor X

• Extrinsic pathway begins with the release of thromboplastin from

damaged tissue

• Intrinsic pathway begins with the activation of factor XII

– Activated factor X, factor V, phospholipids, and Ca2+ form

prothrombinase

– Prothrombin is converted to thrombin by prothrombinase

– Fibrinogen is converted to fibrin by thrombin

 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:
 • Cross-links fibrin

• Strengthens and stabilizes the clot

– Away from the site of injury anticoagulants in the blood, such as

antithrombin and heparin, prevent clot formation

Clot Retraction and Fibrinolysis

 Clot retraction: stabilization of the clot by squeezing serum from the

fibrin strands

– Results from the contraction of platelets, which pull the edges of

damaged tissue closer together

– Serum, which is plasma minus fibrinogen and some clotting factors,

is squeezed out to the clot

 Thrombin and tissue plasminogen activator activate plasmin, which

dissolves fibrin (fibrinolysis)

Blood Grouping

 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

 Transfusion reactions occur when mismatched blood is infused

 Antibodies can bind to the donor’s RBC antigens, resulting in
agglutination or hemolysis of RBCs, leading to

– Diminished oxygen-carrying capacity

– Clumped cells that impede blood flow

– Ruptured RBCs that release free hemoglobin into the bloodstream

Blood Antigens Anti-Body

type Present Present
A B Anti Anti B
A
AB + + - -
B - + + -
A + - - +
O - - + +

ABO Blood Group

 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)

Rh Blood Group

 Rh-positive blood has certain Rh antigens (the D antigen), whereas Rh-

negative blood does not
 Antibodies against the Rh antigen are produced when a Rh-negative
person is exposed to Rh-positive blood
 The Rh blood group is responsible for hemolytic disease of the
newborn, which can occur when the fetus is Rh-positive and the
mother is Rh-negative
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