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THE CARDIOVASCULAR SYSTEM: BLOOD
INTRODUCTION
The cardiovascular system is made up of three components: blood, blood
vessels, and the heart. Blood is a fluid that transports oxygen from the lungs and
nutrients to the cells and carries away carbon dioxide and other waste products. It is used
to transport various substances, helps with protection against disease, and helps to
regulate many life processes. Blood is both a tissue and a fluid. Because it is a collection
of connective tissue that serve particular functions, blood is a tissue. But these cells are
also suspended in a liquid portion called plasma (the extracellular matrix), which makes
the blood a fluid. Routine examination and analysis of its differences by health care
professionals through blood tests can help to determine the causes of different diseases.
Hematology is the study of blood, blood forming tissues, and disorders associated with
those tissues. The needs of cells for oxygen and nutrients are met by both blood and
interstitial fluid. Interstitial fluid is constantly renewed by the blood and consists of a
watery fluid that bathes body cells. Water and nutrients that are brought into the
gastrointestinal tract and oxygen brought into the lungs are transported by the blood, then
diffuse into the interstitial fluid, to which they are diffused into the body cells. In an
opposing action, carbon dioxide and other wastes move from the body cells into the
interstitial fluid and then into blood to be transported into other organs for elimination
from the body.
The heart is the muscle that pumps blood throughout the body. Blood vessels
transport blood from the heart throughout the body cells and return the blood from the
cells back to the heart. The largest blood vessels, the arteries, carry oxygenated blood
from the heart to smaller vessels called arterioles. From the arterioles, oxygenated blood
enters capillaries where gas exchange between the blood and the cells takes place.
Oxygen and nutrients are filtered into the body cells as carbon dioxide and other waste is
filtered out of the cells. The capillaries, with unoxygenated blood, form united vessels
called venules. These venules in turn connect, on their way back to the heart, to form
bigger blood vessels called veins.
FUNCTIONS OF BLOOD
Blood is a liquid connective tissue that works closely with many other fluids of
the body. Interstitial fluid, lymph, cerebrospinal fluid, and aqueous humor to name a few
are developed in and continually replenished by the blood. These extracellular fluids
help to protect, nourish and exchange materials with every cell in the body. The blood
has three general functions:
1. Transportation, Blood transports oxygen from the lungs to the cells of the body,
and likewise carbon dioxide from the cells for elimination from the lungs. The
gastrointestinal tract delivers nutrients through the blood to the cells and
hormones from glands to other body cells.
2. Regulation, Blood helps to regulate pH through buffers thereby maintaining
homeostasis. Heat absorbing and coolant properties of water in blood plasma
helps to adjust body temperature through the skin. The water content of cells is
influenced through blood osmotic pressure.
3. Protection, Blood has the ability to clot, which can protect the cardiovascular
system against excessive loss after an injury. White blood cells carrying
phagocytosis as well as several blood proteins including antibodies, interferons,
and complement, help to protect against disease in many ways.
PHYSICAL CHARACTERISTICS OF BLOOD
Blood is denser and more viscous than water and therefore, flows more slowly
than water. The color of blood when saturated with oxygen is bright red and when
unoxygenated is much darker, from dark red to purple. Blood has a slightly alkaline pH
between 7.35 to 7.45 and a slightly higher temperature of about 38 degrees Celsius or
100.4 degrees Fahrenheit. Total blood volume in an average adult male is 5-6 liters (1.5
gal) and in an average adult female 4-5 liters (1.2 gal).
COMPONENTS OF BLOOD
Whole blood consists of (1) formed elements, which are cells and cell fragments,
and (2) blood plasma, a watery liquid extracellular matrix that consists of dissolved
substances. If a blood sample is centrifuged in a vial, layers will develop with the cells
on the bottom layer and the lighter weight plasma in the top layer. Blood is
approximately 55% plasma and 45% formed elements. Of the formed elements, about
99% are red blood cells (RBCs) and less than 1% consists of white blood cells (WBCs)
and platelets. They form a buffy coat, which is a thin layer between PBCs and blood
plasma in centrifuged blood.
-Blood Plasma
When the formed elements are removed from blood, what is left is called blood
plasma. Plasma consists of about 91.5% water and 8.5% solutes, mostly proteins. The
proteins that are confined to blood are known as plasma proteins. Liver cells known as
hepatocytes synthesized many of the plasma proteins, including albumins, globulins, and
fibrinogen. Certain blood cells develop into cells that produce gamma globulins. Also
known as immunoglobulin’s or antibodies, these plasma proteins are produced during
certain immune responses. Production of antibodies is stimulated with the presence of
antigens such as viruses or bacteria. Antibodies bind to those antigens that signal their
production and then eliminate the invading antigen.
Other solutes in plasma are nutrients, electrolytes, waste products such as uric
acid, urea, ammonia, bilirubin, and creatinine as well as regulatory substances such as
enzymes, hormones and gases.
-Formed Elements
Red blood cells (RBCs), white blood cells (WBCs), and platelets all make up the
formed elements. Unlike platelets, which are cell fragments, RBCs and WBCs are living
cells. RBCs and platelets have very limited roles, whereas WBCs have many general
functions. Many different types of cells are considered WBCs with different roles and
appearances, these include neutrophils, lymphocytes, monocytes, eosinophils, and
basophils. Of the WBCs- neutrophils, eosinophils and basophils are considered Granular
leukocytes because they contain granules that are visible under light microscope after
staining. The WBCs that are agranular leukocytes are monocytes, T and B lymphocytes
and natural killer cells because they don’t contain the visible granules.
Hematocrit is the percentage of the total blood volume occupied by RBCs.
Present more in males than females, the hormone testosterone stimulates synthesis of a
hormone called erythropoietin (EPO) by the kidneys. EPO stimulates production of
RBCs. A significant drop in hematocrit indicates anemia. Men tend to have higher
hematocrit levels than women, especially during reproductive years, due to more
testosterone and possibly due to the loss of blood during menstration. Polycythemia or
unusually high hematocrit, may be caused by dehydration, tissue hypoxia, unregulated
RBC production or blood doping by athletes.
FORMATION OF BLOOD CELLS
Lymphocytes can live for years, though most formed element die and are replaced
within hours to weeks. RBCs and platelets in circulation are continually regulated by
negative feedback systems, however WBC numbers vary according to their need for
response to invading pathogens and antigens. Hemopoiesis is the process in which
formed elements are developed. Before birth, hemopoiesis first occurs in the yolk sac of
the embryo. Later it occurs in the liver, spleen, lymph nodes and thymus of a fetus. In
the last trimester, red bone marrow becomes the site of hemopoiesis and throughout its
life it will continue to be the source of red blood cells.
Red bone marrow is connective tissue that is highly vascularized and is located
between trabeculae of spongy bone tissue. Less than 0.1% of red bone marrow cells
come from mesenchyme and are called pluripotent stem cells. These cells have the
capacity to develop into many different types of cells.
All bone marrow is red in newborns and are active in blood cell production. The
rate of blood cell production decreases as an individual grows as the red bone marrow is
replaced by yellow bone marrow, which is mostly fat cells. Yellow bone marrow has the
ability to become red bone marrow again if the need arises, such as severe bleeding.
Stem cells found in red bone marrow reproduce themselves, multiply and change
into different cells that then turn into blood cells, macrophages, reticular cells,
adipocytes, and mast cells. Some also change to muscle cells, osteoblasts, an
chondrablasts, to be used as a source of muscle tissue for tissue and organ replacement,
bone and cartilage. Reticular cells make reticular fibers, that support red bone marrow
cells as the framework in the form of stroma. Enlarged and leaky capillaries known as
sinuses, that surround red bone marrow cells and fibers, are where the blood from
nutrient and metaphyseal arteries enter a bone and pass into. Blood cells form and enter
these sinuses and leave the bone through nutrient and periosteal veins. Formed elements,
except for lymphocytes, do not divide after leaving the red bone marrow.
Pluripotent stem cells also make two other types of stem cells, myeloid stem cells
and lymphoid stem cells. Myeloid stem cells turn into red blood cells, platelets,
monocytes, neutrophils, eosinophils, and basophils after developing in the red bone
marrow. Lymphoid stem cells start developing in the red bone marrow but finish
developing in lymphatic tissues, and give rise to lymphocytes. Although stem cells
resemble lymphocytes and appear the same histologically, they do have distinctive cell
identity markers in their plasma membranes.
Myeloid stem cells change to progenitor cells during hemopoiesis and lose the
capability to reproduce themselves. Progenitor cells are committed to giving rise to more
specific elements of blood. Some progenitor cells, known as colony-forming units
(CFUs), have an abbreviation after them designating the mature elements in blood that
they produce. CFU-E produce erythrocytes (red blood cells), CFU-GM produces
granulocytes (specifically neutrophils) and monocytes, and CFU-Meg produce
megakaryocytes. Progenitor cells cannot be distinguished from lymphocytes by
appearance alone. Some myeloid stem cells develop into precursor cells. LT
lymphoblasts and B lymphoblasts, differentiated from Lymphoid stem cells, ultimately
develop into T lymphocytes and B lymphocytes or T cells and B cells.
Cells are called precursor cells in the next generation, also known as blasts and
have a recognizable appearance. Over several division they develop into actual formed
elements of blood.
Hemopoietic growth factors are hormones that regulate the proliferation and
differentiation of particular progenitor cells. The hormone EPO or erythropoietin
increases the number of red blood cellprecursors. The cells located between the kidney
tubules aare the main producers of EPO. RBC production is inadequate and EPO release
slows with renal failure. A hormone produced by the liver, called TPO or thrombopoietin
stimulates platelet formation from megakaryocytes. Cytokines are small glycoproteins
that regulate development of different cell types and are produced by red bone marrow
cells, macrophages, fibroblasts, leukocytes and endothelial cells. Colony-stimulating
factors (CSFs) and interleukins are families of cytokines that are important for
stimulating WBC formation. Cytokines stimulate progenitor cells proliferation in red
bone marrow and help to regulate the cells involved in nonspecific defenses and immune
responses.
RED BLOOD CELLS
Red blood cells (RBCs) or erythrocytes contain the oxygen-carrying protein
hemoglobin. New mature cells must enter circulation at a rate of about 2 million per
second to maintain normal levels of RBCs, this is about equal to the rate of RBC
destruction. Normal healthy adult females have about 4.8 million RBCs per microliter
and normal healthy adult males have about 5.4 million per microliter.
-RBC Anatomy
RBCs are biconcave discs with strong and flexible plasma membrane that allows
them to deform without rupturing as they squeeze through narrow capillaries. Certain
glycolipids in a RBC plasma membrane are antigens that account for various blood
groups, for example Rh and ABO groups. RBCs can not reproduce or carry on extensive
metabolic activities and lack a nucleus as well as other organelles. Hemoglobin
molecules , which constitute about a third of the cell weight, are contained in the cytosol
of RBCs, and were synthesized before loss of the nucleus during production.
-RBC Functions
Red blood cells are specialized for oxygen transport; since they have no nucleus,
all their internal space is available for oxygen to transport. RBCs do not contain
mitochondria and generate ATP without oxygen so they don’t need to use the oxygen
they transport. Because RBCs have a bioconcave shape, they have a much bigger surface
area than a cube or a sphere. This allows a greater surface area for the diffusion of gases
into and out of the RBC. Also, due to the thinness of the surface, rapid diffusion of the
gases are enhanced.
Roughly 280 million hemoglobin molecules are contained in each RBC and each
hemoglobin can carry up to four oxygen molecules. Hemoglobin molecules are made of
a protein called globin, which consists of four nonproteinpigments known as hemes and
four polpeptide chains (two alpha and two beta chains). Each polypeptide chain is bound
by one heme. At the center of each heme ring is an iron ion that can combine with one
oxygen molecule reversibly. The iron of the heme group binds to the oxygen in the lungs
and transports it to where the blood flow in the capillaries and releases it by reversing the
iron0oxygen reaction. The oxygen then diffuses first into the interstitial fluid and then
into cells.
In addition to oxygen transport, the hemoglobin transports about 13% of the waste
product of metabolism, carbon dioxide. The carbon dioxide in the blood flowing through
the capillaries combines with the amino acids in the globin part of hemoglobin, is
transported through the blood to the lungs and released to be exhaled.
Hemoglobin also plays a role in the regulation of blood pressure and blood flow.
Nitric Oxide (NO), a gaseous hormone that is produced by endothelial cells in the blood
vessels, binds to hemoglobin. Hemoglobin releases NO under some circumstances
causing vasodilation, an increase in the diameter of the blood vessel by relaxing the
vessel wall of the smooth muscle. Vasodilation helps by improving blood flow and
enhancing oxygen delivery to cells.
-RBC Life Cycle
With all that the RBC endures, their life span is only about 120 days. RBCs cannot
synthesize new components without a nucleus and other organelles to replace damaged
ones. With age, the plasma membrane is more fragile and likely to rupture. RBCs that
rupture are removed from circulation and destroyed once they get to the spleen or liver,
by fixed phagocytic macrophages.
-Erythropoiesis; Producion of RBC’s
Erythropoiesis is the production of RBCs and it starts with a precursor cell known as a
proerythroblast in the red bone marrow. The proerythroblast starts producing cells that
synthesize hemoglobin by dividing many times. A cell becomes a reticulocyte by
ejecting its nucleus near the end of the developmental sequence. The center of the cell
indents with the loss of the nucleus and creates the distinctive concave shape.
Reticulocytes are made of about 34% hemoglobin and retain some of the cell bodies.
After they leave the red bone marrow and into the bloodstream, they squeeze through
holes in the capillaries. Within 1-2 days, reticulocytes develop into erythrocytes or
mature RBCs.
Cell destruction and erythropoiesis occur at roughly the same pace. RBC
production is increased if the oxygen carrying capacity of blood decreased. Hypoxia is a
cellular oxygen deficiency and can occur if there is not enough oxygen in the blood.
Oxygen delivery can be decreased by anemia, high altitude, iron deficiency, a lack of
amino acids and Vitamin B12 to name a few. Also, circulatory problems that reduce
oxygen delivery by slowing blood flow to tissues can cause hypoxia. Kidney release of
erythropoietin is stimulated to combat hypoxia. The red bone marrow increases
production of proerythroblasts into reticulocytes when erythropoietin circulates through
the blood. More oxygen can be delivered to the body tissues when the number of RBCs
is increased.
Premature newborns are more likely to exhibit anemia, due to inadequate
production of erythropoietin. Less sensitive to hypoxia than the kidneys, the liver
produces most EPO during the first weeks after birth and as a result newborns less likely
to respond with EPO as well as adults do. The loss of fetal hemoglobin makes anemia
worse as fetal hemoglobin carries about 30% more oxygen.
-Blood Group Systems
Over 100 different types of antigens, of which at least 14 are currently
recognized, have been found on the surface of RBCs. Scientists and health care
professionals are able to identify a persons blood as belonging to one group system, as
the antigens appear in characteristic patterns. The presence or absence of certain
antigens on the surface of the RBCs plasma membrane characterizes each blood group
system. According to the ABO blood grouping system the symbols A and B are based on
antigens. People who have blood type A manufacture only antigen A and type B only
manufacture antigen B. Those that manufacture both are type AB and those that
manufacture neither are type O.
The Rh blood grouping system is based on those individuals whose erythrocytes
have or lack the Rh antigen. Those who possess the antigen are (+) and those that lack it
are (-). Rh is so named because it was first worked out using the blood of a Rhesus
monkey.
Classifying blood according to having or lacking antigens is important
information when a transfusion is given. A transfusion is the transfer of whole blood or
blood components into the bloodstream. One person’s RBCs can be recognized as
foreign by antibodies in their plasma when transfused into someone with a different
blood type. Those RBCs will be attacked by antibodies and undergo hemolysis,
dispersing hemoglobin into the plasma and causing renal damage.
WHITE BLOOD CELLS
-WBC Anatomy and Types
White blood cells (WBCs) or leukocytes have a nucleus and do not contain
hemoglobin. WBCs are either granular or agranular, depending on if they contain
cytoplasmic vesicle that are made seen when stained and viewed through a light
microscope. Granular leukocytes are neutrophils, eosinophil, and basophils: whereas
agranular leukocytes are monocytes and lymphocytes. Monocytes and granular
leukocytes come from myeloid stem cells and lymphocytes come from lymphoid stem
cells.
---Granular Leukocytes
The granules, after staining, are displayed with distinctive coloration when seen
under a light microscope. The following are granular leukocytes:



Neutrophil- The granules are smaller, evenly distributed and pale lilac in color
making them neutrophilic. The nucleus has 2-5 lobes, and are connected by thin
strands of nuclear material. The number of nuclear lobes increase as the cells age.
Older neutrophils are often called polymorphonuclear leukocytes because they
have several differently shaped nuclear lobes.
Eosinophil- The large, uniform sized granules are eosinophilic as they stain redorange with acidic dyes. The nucleus is usually not obscured or coverd by the
granules, which have tow or three lobes connected by a thick strand or a thin
strand of nuclear material.
Basophil- The variable sized, round granules are basophilic and stain blue-purple
with basic dyes. The two lobed nucleus is commonly obscured by the granule.
---Agranular Leukocytes
Even though the granules are not visible under a light microscope, these
leukocytes do possess granules. The following are characteristics of agranular
leukocytes:

Lynphocyte- The lymphocyte nucleus stains dark and is round or slightly
indented. The cytoplasm forms a rim around the nucleus and stains sky blue.
More cytoplasm is visible with a larger cell. Lymphocytes are classified as large
or small according to cell diameter which is clinically useful in acute viral
infections and some immunodeficiency diseases.

Monocyte- The monocyte has a nucleus in a kidney shape or horseshoe shape
and a cytoplasm that is blue gray with a foamy appearance, owing the appearance
and color to very fine azurophilic granules, which are lysosomes. Monocytes
migrate from the blood to the tissues, where they enlarge and become
macrophages. Some are fixed macrophages that reside stationary in particular
tissues. Others are wandering macrophages, which move through the tissues and
gater at infection or inflammation sites.
WBCs and other nucleated body cells have proteins protruding into the extracellular fluid
from their backs called major histocompatibility (MHC) antigens. RBCs lack the MHC
antigens even though they possess blood group antigens.
-WBC Functions
With constant exposure to microscopic organisms, the function of WBCs is to
combatpathogens by phagocytosis or immune response. WBCs can leave the
bloodstream and collect at points of inflammation or pathogen invasion. Granular
leukocytes and monocytes never return to the bloodstream once they leave it to fight
injury or infection. Lymphocytes recirculate continually from blood to interstitial spaces
of tissue to lymphatic fluid and back to blood. Most lymphocytes are in lymphatic fluid
and organs with only 2% circulating in the blood at any given time.
Where as RBC stay within the bloodstream, WBCs can cross capillary walls by
emigration. WBCs roll along the endothelium that forms capillary walls, stick to it, and
then squeeze between endothelial cells. The signals that stimulate emigration through
certain blood vessel vary.
Neutrophils and macrophages can ingest bacteria and dispose of dead matter,
meaning they are active in phagocytosis. Phagocytes are attracted to several different
chemicals released by inflamed tissues and microbes, a phenomenon called chemotaxis.
Neutrophils respond most quickly to tissue destruction by bacteria. A neutrophil
secretes chemicals to destroy an ingested pathogen, once it has engulfed it with the
process of phagocytosis. The chemicals are the enzyme lysozyme, which destroys certain
bacteria, and strong oxidants, such as hydrogen peroxide and the hypochlorite anion,
similar to household bleach. Neutrophils also have proteins thathave a range of antibiotic
activity against bacteria and fungi called defensins. Neutrophils poke holes in microbe
membranes using peptide “spears” formed from granules containing defensins, resulting
in the fatal loss of cellular contents for the invader.
Moncytes are slower to reach an infection site but with larger numbers. When
they arrive, they enlarge and break up into wandering macrophages that phagocytize with
a bigger effect on more microbes. Also, they clean up after an infection.
Basophils leave capillaries, enter tissues at sites of inflammation and release
heparin, histamine and seotonin, thereby intensifying inflammatory reaction and are
involved in allergic reactions.
Eosinophils leave capillaries and enter tissue fluid to release enzymes, like
histaminase, that counter the effects of histamine and other mediators of inflammation in
allergic reactions. They also phagocytize antigen-antibody complexes as well as are
effective against certain parasitic worms. An allergic reaction or parasitic infection are
indicated in a high eosinophil count.
Lymphocytes are the front line defense in immune responses. Only a small
portion of lymphocytes are actually in the blood at any given time as the majority are
continually moving among lymphoid tissues, lymph and blood. Three types of
lymphocytes are B cells, T cells, and natural killer (NK) cells. T cells attack viruses,
fungi, transplanted cells, cancer cells, and some bacteria. B cells produce antibodies that
help destroy bacteria and inactivate their toxins. Natural killer cells attack a wide variety
of infectious microbes and tumor cells.
A physician will order a differential WBC count to see if there is inflammation or
infection, monitor blood disorders, the effects of possible poisoning by drugs or
chemicals, or detect parasitic infection and allergic reaction.
PLATELETS
Hemopoietic stem cells also differentiate into cells that produce platelets. The
hormone thrombopoietin influences myeloid stem cells to develop into megakaryocytecolony-forming cells that then develop into precursor cells called megakaryoblasts.
Maegakaryoblasts turn into megakaryocytes that splinter into 2000-3000 fragments.
Each fragment is a platelet, enclosed by a piece of cell membrane. Platelets come
together to form a plug that fills a gap in the blood vessel wall and helping to stop blood
loss. They also contain chemicals that promote blood clotting, creating chemical
reactions that form a network of insoluble protein threads called fibrin. A bllod clot
consists of fibrin threads, platelets; and any blood cells trapped in the fibrin. In addition
to preventing blood loss, the blood clot pulls the edges of the damaged vessel together to
help the damage heal.
STEM CELL TRANSPLANTS FROM BONE MARROW AND CORDBLOOD
A bone marrow transplant replaces cancerous or abnormal red bone marrow with
healthy red bone marrow to establish normal blood cell counts. Defective red bone
marrow is destroyed with high doses of chemotherapy and radiation before the transplant
takes place. The cancer cells and the patient’s immune system are destroyed in order to
decrease the chance of transplant rejection.
Red bone marrow from a donor is removed form theiliac crest of the hip bone
under general anesthesia with a syringe and is injected into the recipient’s vein. The
marrow that is injected migrates to the red bone marrow cavities and the donor cells
multiply. A more recent advance in obtaining stem cells involves a cord-blood
transplant. The placenta contains stem cells, which may be obtained from the umblilical
cord shortly after birth.