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7. Clot formation
Composition of Blood
Blood is a type of connective tissue that consists of cells and cell fragments
surrounded by a liquid matrix. The cells and cell fragments are the formed
elements, and the liquid is the formed elements account for slightly less than half
and plasma accounts for slightly more than half the total blood volume. The total
blood volume in the average adult is about 4-5 liters (L) in females and 5-6 L in
males. Blood makes up about 8% of total body weight.
Plasma
Plasma is a pale yellow fluid that consists of about 91% water; 7% proteins; and 2%
other substances, such as ions, nutrients, gases, and waste products. Plasma
proteins include albumin, globulins, and fibrinogen. Albumin makes up 58% of the
plasma proteins. Although the osmotic pressure of blood results primarily from
sodium chloride, albumin makes and important contribution. The water balance
between blood and tissues is determined by the movement of water into and out of
the blood by osmosis. Globulins account for 38% of the plasma proteins. Some
globulins, such as antibodies and complement, are part of the immune system.
Other globulins and albumin function as transport molecules because they bind to
molecules such as hormones and carry them in the blood throughout the body.
Some globulins are clotting factors, which are necessary for the formation of blood
clots. Fibrinogen is a clotting factor that constitutes 4% of plasma proteins.
Activation of clotting factors results in the conversion of fibrinogen into fibrin, a
threadlike protein that forms blood clots. Serum is plasma without the clotting
factors.
Formed Elements
About 95% of the volume of the formed elements consists of red blood cells (RBCs),
or erythrocytes. The remaining 5% of the volume of the formed elements consists of
white blood cells (WBSs), or leukocytes, and cell fragments called platelets, or
thrombocytes. Red blood cells are 700 times more numerous than white blood cells
and 17 times more numerous than platelets.
Normal red blood cells are disk-shaped cells with edges that are thicker than the
center of the cell. The biconcave shape increases the surface area of the red blood
cell compared with a flat disk of the same size. The greater surgace area makes it
easier for gases to move into and out of the red blood cell. In addition, the red blood
cell can bend or fold around its thin center, decreasing its size and enabling it to
pass more easily through small blood vessels.
During their development, red blood cells lose their nuclei and most of their
organelles. Consequently, they are unable to divide. Red blood cells live for about
120 days in males and 110 days in females. The main component of a red blood cell
is the pigmented protein hemoglobin, which accounts for about a third of the cell’s
volume and is responsible for its red color.
Function
The primary functions of red blood cells are to transport oxygen from the lungs to
the various tissues of the body and to assist in the transport of carbon dioxide from
the tissues to the lungs. Oxygen transport is accomplished by hemoglobin, which
consists of four proten chains and four heme groups. Each protein, called a globin,
is bound to one heme, a red-pigmented molecule. Each heme contains one iron
atom, which is necessary for the normal function of hemoglobin. Each iron in a
heme molecule can reversibly associate with an oxygen molecule. Hemoglobin
picks up oxygen in the lungs and releases oxygen in other tissues. Hemoglobin is
responsible for 98.5% of the oxygen transported in blood. The remaining 1.5% is
transported dissolved in plasma.
Because iron is necessary for oxygen transport, it is not surprising that two-
thirds of the body’s iron is found in hemoglobin. Small amounts of iron are required
in the diet to replace the small amounts lost in the urine and feces. Women need
more dietary iron than men do because women lose iron as a result of
menstruation.
All the formed elements of blood are derived from a single population of cells
called stem cells or hemocytoblasts. These stem cells differentiate to give rise to
different cell lines, each of which ends with the formation of a particular type of
formed element. The development of each cell line is regulated by specific growth
factors. That is, the types of formed element derived from the stem cells and how
many formed elements are produced are determined by the growth factors.
White blood cells or leukocytes, are spherical cells that lack hemoglobin. White
blood cells form a thin, white layer of cells between plasma and red blood cells
when the components of blood are separated from each other. They are larger than
red blood cells, and each has a nucleus. Although white blood cells are components
of the blood, the blood serves primarily as a means to transport these cells to other
tissues of the body. White blood cells can leave the blood and move by ameboid
movement through the tissues. In this process, the cell projects a cytoplasmic
extension that attaches to an object. Then the rest of the cell’s cytoplasm flows into
the extension. Two functions of white blood cells are (1) to protect the body against
invading microorganisms and (2) to remove dead cells and debris from the tissues
by phagocytosis.
Each white blood cell type is named according to its appearance in stained
preparations. Those containing large cytoplasmic granules are granulocytes, and
those with very small granules that cannot be easily seen with the light microscope
are agranulocytes.
Basophils, the least common of all white blood cells, contain large
cytoplasmic granules that stain blue or purple with basic dyes. Basophils release
histamine and other chemicals that promote inflammation. They also release
heparin, which prevents the formation of clots.
Eosinophils contain cytoplasmic granules that stain bright red with eosin,and
acidic stain. They often have a two-lobed nucleus. Eosinophils release chemicals
that reduce inflammation. In additions, chemicals from eosinophils are involved with
the destruction of certain worm parasites.
Monocytes are the largest of the white blood cells. After they leave the blood
and enter tissues, monocytes enlarge and become macrophages, which phagocytize
bacteria, dead cells, cell fragments, and any other debris within the tissues. In
addition, macrophages can break down phagocytized foreign substances and
present the processed substances to lymphocytes, which results in activation of the
lyumphocytes.
Platelets
When a blood vessel is damaged, blood can leak into other tissues and interfere
with normal tissue function, or blood can be lost from the body. A small amount of
blood loss from the body can be tolerated, and new blood is produced to replace it.
If a large amount of blood is lost, death can occur. Fortunately, when a blood vessel
is damaged, vascular spasm, platelet plug formation, and blood clotting minimize
the loss of blood.
Platelet Plugs
Blood Clotting
Blood vessel constriction and platelet plugs alone are not sufficient to close large
tears or cuts in blood vessels. When a blood vessel is severely damaged, blood
clotting, or coagulation, results in the formation of a clot. A clot is a network of
threadlike protein fibers, called fibrin, that traps blood cells, platelets, and fluid.
The formation of a blood clot depends on a number of proteins found within
plasma called clotting factors. Normally the clotting factors are inactive and do not
cause clotting. Following injury, however, the clotting factors are activated to
produce a clot.
1. The chemical reactions can be started in two ways: (a) the contact of inactive
clotting factors with exposed connective tissue can result in their activation;
(b) chemicals, such as thromboplastin, released from injured tissues can
cause activation of clotting factors. After the initial clotting factors are
activated, they in turn activate other clotting factors. A series of reactions
results in which each clotting factor activates the next in the series until the
clotting factor prothrombinase is formed.
3. Thrombin converts the inactive clotting factor fibrinogen into its active form,
fibrin, a threadlike protein. A clot is a network of fibrin that traps blood cells,
platelets, and fluid.
At each step of the clotting process, each clotting factor activates many additional
clotting factors. Consequently, a large quantity of clotting factors is activated,
resulting in the formation of the clot.
Most clotting factors are manufacture in the liver, and many of them require vitamin
K for their synthesis. In addition, many of the chemical reaction of clot formation
require Ca2+ and the chemicals release from platelets. Low levels of vitamin K, low
level of Ca2+, low numbers of platelets, or reduced synthesis of clotting factors
because of liver dysfunction can seriously impair the blood-clotting process.
Without control, clotting would spread from the point of its initiation throughout the
entire circulatory system. The blood contains several anticoagulants, which prevent
clotting factors from forming clots. Antithrombin and heparin, fibrinogen is not
converted to fibrin, and no clot forms. Normally there are enough anticoagulants in
the blood to prevent clot formation. At an injury site, however, the activation of
clotting factors is very rapid. Enough clotting factors are activated so that the
anticoagulants can no longer prevent a clot from forming. Away from the injury site
there are enough anticoagulants to prevent clot formation from spreading.
After a clot has formed, it begins to condense into a more compact structure by a
process known as clot retraction. Platelets contain the contractile proteins, actin
and myosin, which operate in a similar fashion to the actin and myosin in muscle.
Platelets form small extensions that attach to fibrin through surface receptors.
Contraction of the extensions pulls on the the fibrin and is responsible for clot
retraction. Serum, which is plasma without the clotting factors, is squeezed out of
the clot during clot retraction.
Retraction of the clot pulls the edges of the damaged blood vessel together,
helping to stop the flow of blood, reducing the probability of infection, and
enhancing healing. The damaged vessel is repaired by the movement of fibroblasts
into the damaged area and the formation of new connective tissue. In addition,
epithelial cells around the wound divide and fill in the torn area.