BLOOD

By Lipsa Routray
Introduction
• Fluid connective tissue
• Liquid extracellular matrix (plasma) + Blood corpuscles/cells
Physical characteristics:
• Denser, more viscous than water, slightly sticky
• Temperature = 38 C
• pH= 7.35- 7.45 (slightly alkaline)
• Colour- Red (due to the presence of haemoglobin)
• Composition = Blood plasma (55%) + Blood corpuscles (45%)
Functions:
i. Transportation: Blood transports O2, CO2, nutrients and hormones to and from body’s cell.
ii. Regulation: Maintain hameostasis of all body fluid. Regulate pH (through use of buffers) and
temperature (through heat absorbing and coolant properties of water in blood plasma).
iii. Protection: Blood clot- Protection against excessive blood loss from cardiovascular system
WBC- Protection against disease through phagocytosis and production of antibodies.
 Albumins (54%)
Components of Blood Plasma Proteins Globulins (38%)
Dissolved (7%) Fibrinogen (7%)
substances(8.5%) Others (1%)
Other Electrolytes,
Water (91.5%) solutes(1.5%) Nutrients, Gases,
Waste products
etc.
Platelets (150,000
- 400,000)
WBCs (5,000 –
10,000)
RBCs (4.8 – 5.4
million)

Serum = Blood Plasma – Clotting factors

I. Blood Plasma
• When the formed elements are removed from blood, a straw colored liquid called blood plasma (or
simply plasma) is left.
• Blood plasma is about 91.5% water and 8.5% solutes, most of which (7% by weight) are proteins.
• Some of the proteins in blood plasma are also found elsewhere in the body, but those confined to
blood are called plasma proteins.
• Hepatocytes (liver cells) synthesize most of the plasma pro teins,which include the albumins (54%
of plasma proteins), globulins(38%),and fibrinogen(7%).
• Certain blood cells develop into cells that produce gamma globulins, an important type of
globulin. These plasma proteins are also called antibodies or immunoglobulins because they are
produced during certain immune responses.
• Besides proteins,other solutes in plasma include electrolytes, nutrients, regulatory substances such
as enzymes and hormones, gases,and waste products such as urea,uric acid,creatinine,am
monia,and bilirubin.
II. Formed elements/ Blood Corpuscles
• The formed elements of the blood include three principal components: red blood
cells (RBCs),white blood cells (WBCs), and platelets.
• RBCs and WBCs are whole cells; platelets are cell fragments. RBCs and platelets
have just a few roles, but WBCs have a number of specialized functions.
 Formed Elements / Blood Corpuscles

Erythrocytes ( RBCs- Leucocytes (WBCs- White Blood Cells) Thrombocytes

Red Blood Cells) (Platelets)

Granulocytes Agranulocytes

Neutrophil Basophil Eisonophil Lymphocytes Monocytes

B-Lymphocytes
Macrophages
T- Lymphocytes

Natural Killer
(NK) cells
 Formation of Blood Cells
• The process by which the formed elements of blood develop is called hemopoiesis or hematopoiesis.
• Before birth, it first occurs in the yolk sac of an embryo and later in the liver, spleen, thymus, and lymph
nodes of a fetus.
• Red bone marrow becomes the primary site of hemopoiesis in the last three months before birth, and
continues as the source of blood cells after birth and throughout life.
• Red bone marrow is a highly vascularized connective tissue located in the microscopic spaces between
trabeculae of spongy bone tissue. It is present chiefly in bones of the axial skeleton, pectoral and pelvic
girdles, and the proximal epiphyses of the humerus and femur.
• About 0.05–0.1% of red bone marrow cells are derived from mesenchyme and are called pluripotent stem
cells (ploo-RIP-o¯-tent; pluri several) or hemocytoblasts. These cells have the capacity to develop into
many different types of cells.
• In newborns all bone marrow is red and thus active in blood cell production. As an in dividual grows and
in adulthood, the rate of blood cell formation decreases; the red bone marrow in the medullary (marrow)
cav ity of long bones becomes inactive and is replaced by yellow bone marrow, which is largely fat cells.
• Under certain condi tions, such as severe bleeding, yellow bone marrow can revert to red bone marrow by
extension of red bone marrow into yellow bone marrow and repopulation of yellow bone marrow by
pluripotent stem cells.
Hormones in Hematopoiesis
• Hemopoietic growth factors: regulate the differentiation and proliferation of particular progenitor
cells.
• Erythropoietin or EPO: increases the number of red blood cell precursors. EPO is produced pri
marily by cells in the kidneys that lie between the kidney tubules (peritubular interstitial cells).
With renal failure, EPO release slows and RBC production is inadequate.
• Thrombopoietin or TPO: is a hormone produced by the liver that stimulates the formation of
platelets (thrombocytes) from megakaryocytes.
• Cytokines: regulate development of different blood cell types. Cytokines are small glycoproteins
that are typically produced by cells such as red bone marrow cells, leukocytes, macrophages,
fibroblasts, and endothelial cells. They generally act as local hormones. Cytokines stimulate
proliferation of progenitor cells in red bone marrow and regulate the activities of cells involved in
nonspecific defenses (such as phagocytes) and immune responses (such as B cells and T cells).
Two important families of cytokines that stimulate white blood cell formation are colony-
stimulating factors (CSFs) and interleukins.
 A. Erythrocyte/ Red Blood Cells (RBCs)
• Red blood cells (RBCs) or erythrocytes contain the oxygen-carrying protein hemoglobin, which is a pigment
that gives whole blood its red color.
• A healthy adult male has about 5.4 million red blood cells per microliter ( L) of blood,* and a healthy adult
female has about 4.8 million. (One drop of blood is about 50 L.)
• To maintain normal numbers of RBCs, new mature cells must enter the circulation at the astonishing rate of
at least 2 million per second, a pace that balances the equally high rate of RBC destruction.
RBC Anatomy
• RBCs are biconcave discs with a diameter of 7–8 m.
• Mature red blood cells have a simple structure. Their plasma membrane is both strong and flexible, which
allows them to deform without rupturing as they squeeze through narrow capillaries.
• Certain glycolipids in the plasma membrane of RBCs are antigens that account for the various blood groups
such as the ABO and Rh groups.
• RBCs lack a nucleus and other organelles and can neither reproduce nor carry on extensive metabolic
activities.
• The cytosol of RBCs contains hemoglobin molecules; these important molecules are synthesized before loss
of the nucleus during RBC production and constitute about 33% of the cell’s weight.
 RBC Physiology
• Red blood cells are highly specialized for their oxygen transport function. Because mature RBCs
have no nucleus, all their internal space is available for oxygen transport.
• Because RBCs lack mitochondria and generate ATP anaerobically (without oxygen), they do not use
up any of the oxygen they transport.
• Even the shape of an RBC facilitates its function. A biconcave disc has a much greater surface area
for the diffusion of gas molecules into and out of the RBC than would, say, a sphere or a cube.
Haemoglobin:
• Each RBC contains about 280 million hemoglobin molecules.
• A hemoglobin molecule consists of a protein called globin, composed of four polypeptide chains
(two alpha and two beta chains); a ringlike nonprotein pigment called a heme is bound to each of the
four chains.
• At the center of each heme ring is an iron ion (Fe2 ) that can combine reversibly with one oxygen
molecule, allowing each hemoglobin molecule to bind four oxygen molecules.
O2 and CO2 Transport:
• Each oxygen molecule picked up from the lungs is bound to an iron ion. As blood flows through tissue
capillaries, the iron–oxygen reaction reverses.
• Hemoglobin releases oxygen, which diffuses first into the interstitial fluid and then into cells.
• Hemoglobin also transports about 23% of the total carbon dioxide, a waste product of metabolism.
• Blood flowing through tissue capillaries picks up carbon dioxide, some of which combines with amino
acids in the globin part of hemoglobin.
• As blood flows through the lungs, the carbon dioxide is released from hemoglobin and then exhaled.
Regulation of blood flow and blood pressure:
• The gaseous hormone nitric oxide (NO), produced by the endothelial cells that line blood vessels, binds
to hemoglobin.
• Under some circumstances, hemoglobin releases NO.
• The released NO causes vasodilation, an increase in blood vessel diameter that occurs when the smooth
muscle in the vessel wall relaxes.
• Vasodilation i proves blood flow and enhances oxygen delivery to cells near the site of NO release.
 RBC Life Cycle
• Red blood cells live only about 120 days because of the wear and tear their plasma membranes undergo as
they squeeze through blood capillaries.
• Without a nucleus and other organelles, RBCs cannot synthesize new components to replace damaged
ones.
• The plasma membrane becomes more fragile with age, and the cells are more likely to burst, especially as
they squeeze through narrow channels in the spleen.
• Ruptured RBCs are removed from circulation and destroyed by fixed phagocytic macrophages in the
spleen and liver, and the breakdown products are recycled, as follows:
1. Macrophages in the spleen, liver, or red bone marrow phagocytize ruptured
and worn-out red blood cells.
2. The globin and heme portions of hemoglobin are split apart.
3. Globin is broken down into amino acids, which can be reused to synthesize
other proteins.
4. Iron is removed from the heme portion in the form of Fe3 , which associates
with the plasma protein transferrin, a transporter for Fe3 in the bloodstream.
5. In muscle fibers, liver cells, and macrophages of the spleen and liver, Fe3
detaches from transferrin and attaches to an iron-storage protein called ferritin.
6. Upon release from a storage site or absorption from the gastrointestinal tract,
Fe3 reattaches to transferrin.
7. The Fe3–transferrin complex is then carried to red bone marrow, where
RBC precursor cells take it up through receptor-mediated endocytosis for use in
hemoglobin synthesis. Iron is needed for the heme portion of the hemoglobin
molecule, and amino acids are needed for the globin portion. Vitamin B12 is
also needed for the synthesis of hemoglobin.
8. Erythropoiesis in red bone marrow results in the production of red blood
cells, which enter the circulation.
9. When iron is removed from heme, the non-iron portion of heme is
converted to biliverdin, a green pigment, and then into bilirubin , a yellow-
orange pigment.
10. Bilirubin enters the blood and is transported to the liver.
11. Within the liver, bilirubin is released by liver cells into bile, which passes
into the small intestine and then into the large intestine.
12. In the large intestine, bacteria convert bilirubin into urobilinogen.
13. Some urobilinogen is absorbed back into the blood, converted to a yellow
pigment called urobilin, and excreted in urine.
14. Most urobilinogen is eliminated in feces in the form of a brown pigment
called stercobilin, which gives feces its characteristic color.
B. Leucocytes/White Blood Cells (WBCs)
Unlike red blood cells, white blood cells or leukocytes have nuclei and do not contain hemoglobin.
Types of WBCs:
• WBCs are classified as either granular or agranular, depending on whether they contain
conspicuous chemical-filled cytoplasmic granules (vesicles) that are made visible by staining
when viewed through a light microscope.
• Granular leukocytes include neutrophils, eosinophils, and basophils; agranular leukocytes include
lymphocytes and monocytes.
• Monocytes and granular leukocytes develop from a myeloid stem cell, and lymphocytes develop
from a lymphoid stem cell.
i. Granular Leukocytes:
• There are 3 types of granular WBCs- Eosinophil, Basophil and Neutrophil.
• After staining, each of the three types of granular leukocytes displays conspicuous granules with
distinctive coloration that can be recognized under a light microscope.
a. Eosinophil (eosin loving)
• The large, uniform-sized granules. They stain red-orange with acidic dyes.
• The granules usually do not cover or obscure the nucleus, which most often has two lobes
connected by a thick strand of chromatin.
b. Basophil (basic loving)
• The round, variable-sized granules. They stain blue-purple with basic dyes. The granules
commonly obscure the nucleus, which has two lobes.
c. Neutrophil
• Granules are smaller, evenly distributed, and pale lilac in colour.
• The nucleus has two to five lobes, connected by very thin strands of chromatin. As the cells age,
the number of nuclear lobes increases.
• Because older neutrophils have several differently shaped nuclear lobes, they are often called
polymorphonuclear leukocytes (PMNs), polymorphs, or “polys.”
• Younger neutrophils are often called bands because their nucleus is more rod-shaped.
ii. Agranular Leukocytes:
• Even though so-called agranular leukocytes possess cytoplasmic granules, the granules are not visible
under a light microscope because of their small size and poor staining qualities.
a. Lymphocytes
• The nucleus of a lymphocyte is round or slightly indented and stains darkly.
• The cytoplasm stains sky blue and forms a rim around the nucleus.
• The larger the cell, the more cytoplasm is visible. Lymphocytes may be as small as 6–9 μm in diameter or
as large as 10–14 μm in diameter.
• Although the functional significance of the size difference between small and large lymphocytes is unclear,
the distinction is still clinically useful because an increase in the number of large lymphocytes has
diagnostic significance in acute viral infections and in some immunodeficiency diseases.
• There are three types of lymphocytes:
1. T- lymphocytes (T cells)
2. B- lymphocytes (B cells)
3. Natural Killer (NK) cells.
b. Monocytes:
• Monocytes are 12–20 m in diameter.
• The nucleus of a monocyte is usually kidney shaped or horseshoe-shaped, and the cytoplasm is blue-gray
and has a foamy appearance.
• The color and appearance are due to very fine azurophilic granules, which are lysosomes.
• The blood transports monocytes from the blood into the tissues, where they enlarge and differentiate into
macrophages ( large eaters).
• Some become fixed macrophages, which means they reside in a particular tissue; examples are alveolar
macrophages in the lungs, macrophages in the spleen, and stellate reticuloendothelial (Kupffer) cells in the
liver.
• Others become wandering macrophages, which roam the tissues and gather at sites of infection or
inflammation.
Functions of WBCs
• In a healthy body, some WBCs, especially lymphocytes, can live for several
months or years, but most live only a few days.
• During a period of infection, phagocytic WBCs may live only a few hours.
WBCs are far less numerous than red blood cells; at about 5000–10,000
cells per L of blood, they are outnumbered by RBCs by about 7001.
• Leukocytosis (loo-ko¯-sı ¯-TO ¯-sis), an increase in the number of WBCs
above 10,000/ L, is a normal, protective response to stresses such as
invading microbes, strenuous exercise, anesthesia, and surgery.
• An abnormally low level of white blood cells (below 5000/ L) is termed
leukopenia (loo-ko¯-PE E ¯-ne ¯-a). It is never beneficial and may be caused
by radiation, shock, and certain chemotherapeutic agents.
• Neutrophils and macrophages are active in phagocytosis; they can ingest bacteria and dispose of
dead matter.
• Several different chemicals released by microbes and inflamed tissues attract phagocytes, a
phenomenon called chemotaxis.
• The substances that provide stimuli for chemotaxis include toxins produced by microbes; kinins,
which are specialized products of damaged tissues; and some of the colony-stimulating factors
(CSFs).
• The CSFs also enhance the phagocytic activity of neutrophils and macrophages.
• Among WBCs, neutrophils respond most quickly to tissue de struction by bacteria. After engulfing
a pathogen during phagocytosis, a neutrophil unleashes several chemicals to destroy the
pathogen.
• These chemicals include the enzyme lysozyme, which destroys certain bacteria, and strong
oxidants, such as the superoxide anion (O2 ), hydrogen peroxide (H2O2), and the hypochlorite
anion (OCl ), which is similar to household bleach.
• Neutrophils also contain defensins, proteins that exhibit a broad range of antibiotic activity against
bacteria and fungi.
• Lymphocytes are the major soldiers in immune system battles (described in detail in Chapter 22).
Most lymphocytes continually move among lymphoid tissues, lymph, and blood, spending only a
few hours at a time in blood. Thus, only a small proportion of the total lymphocytes are present in
the blood at any given time. Three main types of lymphocytes are B cells, T cells, and natural killer
(NK) cells. B cells are partic ularly effective in destroying bacteria and inactivating their toxins. T
cells attack viruses, fungi, transplanted cells, cancer cells, and some bacteria, and are responsible
for transfusion reactions, allergies, and the rejection of transplanted organs. Immune responses
carried out by both B cells and T cells help combat infection and provide protection against some
diseases. Natural killer cells attack a wide variety of infectious microbes and certain spontaneously
arising tumor cells.
• Eosinophils leave the capillaries and enter tissue fluid. They are believed to release enzymes, such
as histaminase, that com bat the effects of histamine and other substances involved in inflammation
during allergic reactions. Eosinophils also phago cytize antigen–antibody complexes and are
effective against cer tain parasitic worms. A high eosinophil count often indicates an allergic
condition or a parasitic infection.
C. Thrombocytes/Platelets
Formation:
• Besides the immature cell types that develop into erythrocytes and leukocytes,
hemopoietic stem cells also differentiate into cells that produce platelets.
• Under the influence of the hormone thrombopoietin, myeloid stem cells develop
into megakaryocyte-colony-forming cells that in turn develop into precursor cells
called megakaryoblasts.
• Megakaryoblasts transform into megakaryocytes, huge cells that splinter into
2000 to 3000 fragments.
• Each fragment, enclosed by a piece of the plasma membrane, is a platelet
(thrombocyte).
• Platelets break off from the megakaryocytes in red bone marrow and then enter
the blood circulation.
Physical properties:
• Between 150,000 and 400,000 platelets are present in each L of blood.
• Each is disc-shaped, 2–4 m in diameter, and has many vesicles but no
nucleus.
Functions:
• Platelets help stop blood loss from damaged blood vessels by forming a
platelet plug.
• Their granules also contain chemicals that, once released, promote blood
clotting.
• Platelets have a short life span, normally just 5 to 9 days.
• Aged and dead platelets are removed by fixed macrophages in the spleen
and liver.