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Blood.
It is “the river of life” that suggest within us. It transported everything that must be
carried from one place to another within the body such as nutrients, wastes, and body
heat through blood vessels. For centuries, long before modern medicine, people
recognize that blood was vital and its loss was always consider a possible of death.
Among all the body tissue, blood is the only one that is in fluid form although
blood appears to be a thick, homogenous liquid, the microscope reveals it has both
solid and liquid components.
Function:
Distribution: delivering oxygen from the lungs and nutrients from the digestive tract to
all body cells. It transports metabolic waste products from cells to elimination sites.
(Lungs for distribution of carbon dioxide, and kidney for the waste products from
alignmentary tract.)
Protection: Preventing blood loss when a blood vessel is damaged, platelets and
plasma proteins initiate clot formation, halting blood loss. Preventing infection drifting
along in the blood are antibodies, complement proteins, and white blood cells, all of
which help defend the body against invaders such as bacteria and viruses.
Plasma.
Is approximately 90 percent of water, is liquid part of the blood. Over 100 different
substances is dissolved in this straw-colored fluid. Examples of this are salts
(electrolytes), respiratory gasses, hormones, plasma proteins, and various wastes
products of cell metabolism.
Components of Plasma
Salts (Electrolytes)
•Sodium Osmotic balance.
•Potassium pH buffering, regulation of membrane
•Calcium permeability.
•Magnesium
•Chloride
•Bicarbonate.
Plasma Proteins
Structural characteristics.
Erythrocytes or the red blood cell(RBCS) are small cells, about 7.5 micro millimeter in
diameter. It shapes like a biconcave disc, flattened with pressed center. They appear
lighter in color at their centers than at their edges. Erythrocytes look like a miniature
doughnuts when viewed on a microscope. A mature RBC is bound in the plasma
membrane, but lack a nucleus and essentially no organelles. In fact, they are little more
than bags of hemoglobin, the RBC protein that functions in gas exchange and gas
transport. Some protein present eliminates bad toxins that may cause harm to the body.
This protein is called the anti-oxidant. An anti-oxidant also eliminates bad oxygen in the
body.
Women typically have a lower number of RBC count than men. 4.3-5.2 million cells per
micro liter of blood versus 501-508 million cells. When the number of RBC increase
beyond the normal range, blood viscosity rises and blood flows more slowly. Similarly,
as the number of red blood cell drops below normal the lower end of the range, the
blood thins and flows more rapidly.
Function
RBCs are completely dedicated to their job of respiratory gas transport. Hemoglobin
makes RBC color, binds easily and reversibility with oxygen, and most oxygen carried in
blood is bound to hemoglobin. Normal values for hemoglobin are 14-20 grams per
100ml of blood in infants, 13-18gl100ml in adult males, and 12-16 female. Hemoglobin
is made up of the protein globin bound to the red hemi pigment. Globin consists of four
chains two alpha and two beta. Each bound to a ring like hemi group. Each hemi group
bears an atom of iron set like a jewel in its center. Since each iron atom can combine
reversibility with one molecule of oxygen, a hemoglobin molecule can transport four
molecules of oxygen. A single red blood cell contains about 250 million hemoglobin
molecules, so each of these tiny cells can scoop up about 1 billion molecules of oxygen.
Production of RBC
Leukocytes
Although leukocytes, or White Blood Cells are far less numerous than Red blood cells,
they are crucial to body defense against disease. On average, there are 4000- 1000
WBC’s per mm3, and they account for less than 1 percent of total blood volume. White
blood cells are the only complete cells in blood; that is, they contain nuclei and the usual
organelles.
Leukocytes form protective, movable army that helps defend the body against
damage by bacteria, viruses, parasites, and tumor cells. As such, they have some very
special characteristics. Red Blood Cells are confined to the bloodstream and carry out
their function in the blood. White blood cells, by the contrast, are process called
“diapedesis” . the circulatory system is simply their means of transportation to areas of
body where their services are needed for inflammatory or immune response.
WBCs can locate areas of tissues damage and infection in the body by
responding to certain chemicals that diffuse from the damaged cells. This capability is
called positive chemotaxis. Once they have “ caught scent”, WBCs move through the
tissue spaces by ameboid motion. By fallowing the diffusion gradient, they pinpoint
areas tissue damage and rally round in large numbers to destroy microorganism or
dead cells.
Whenever WBCs mobilized for action , the body speeds up their production, and
as many as twice the normal WBCs may appear in the blood within a few hours. A total
WBCs count above 11,000 cells/mm3 is referred as leukocytosis. Leukocytosis
generally indicates bacterial or viral infection stewing in the body. The opposite
condition, leucopenia is an abnormally low WBC count. It is commonly caused by
certain drugs, such as corticosteroids and anticancer agents.
GRANULOCYTE
Neutrophils, the most numerous of white blood cell, account for 50-70% of WBC
population. Neutrophils are about twice as large as erythrocytes. The neutrophils
cytoplasm stains pale lilac and contains very fine granules. They called neutrophils
because their granules take up both basic and acidic dyes. Together, the two types
granules give the cytoplasm a lilac color. Some of this granules contains hydrolytic
enzymes, and are regarded as lysosomes. Other especially the smaller granules,
contain potent antimicrobial proteins, called defensins. Neutrophil nuclei consist of three
to six lobes. Because of this nuclear variability, they are often called polymorph nuclear
leukocytes or simply polys.
Neutrophils are chemically attracted to sites of inflammation and are active phagocytes.
They are especially partial to bacteria and some fungi, and bacterial killing is promoted
by a process called a respiratory burst. In the respiratory burst, oxygen is actively
metabolized to produce potent germ-killer oxidizing substances such as bleach and
hydrogen peroxide, and defensin-mediated lysis occurs. It appears that when the
granules containing defensins are merged with a microbe-containing phagosome, the
defensins form peptide “spears” that pierce holes in the membrane of the ingested “foe.”
Neutrophils are our body’s bacteria slayers, and their numbers increase explosively
during acute bacterial infections such as meningitis and appendicitis.
Eosinophils account for 2–4% of all leukocytes and are approximately the size
of neutrophils. Their deep red nucleus usually resembles an old-fashioned
telephone receiver; that is, it has two lobes connected by a broad band of nuclear
material. Large, coarse granules that stain from brick red to crimson with acid
(eosin) dyes pack the cytoplasm. These granules are lysosome-like and filled with
a unique variety of digestive enzymes. However, unlike typical lysosomes, they
lack enzymes that specifically digest bacteria.
The most important role of eosinophils is to lead the counterattack against
parasitic worms, such as flatworms (tapeworms and flukes) and roundworms
(pinworms and hookworms) that are too large to be phagocytized. These worms
are ingested in food (especially raw fish) or invade the body via the skin and then
typically burrow into the intestinal or respiratory mucosae. Eosinophils reside in
the loose connective tissues at the same body sites, and when a parasitic worm
“prey” is encountered, they gather around and release the enzymes from their
cytoplasmic granules onto the parasite’s surface, digesting it away. Eosinophils
may also lessen the severity of allergies by inactivating certain inflammatory
chemicals released during allergic reactions.
Basophils are the rarest white blood cells, averaging only 0.5–1% of the leukocyte
population. Their cytoplasm contains large, coarse, histamine-containing
granules that have an affinity for the basic dyes (basophil = “base loving”)
and stain purplish-black. Histamine is an inflammatory chemical that acts as
a vasodilator (makes blood vessels dilate) and attracts other white blood
cells to the inflamed site; drugs called antihistamines counter this effect.
The deep purple nucleus is generally U or S shaped with two or three
conspicuous constrictions. Granulated cells similar to basophils, called
mast cells, are found in connective tissues. Although mast cell nuclei tend
to be more oval than lobed, the cells are similar microscopically, and both
cell types bind to a particular antibody (immunoglobulin E) that causes the
cells to release histamine. However, they arise from different cell lines.
Cytoplasm has few large blue-purple granules; U-or S shape nucleus with
constrictions, stain dark blue. It contains histamine (vasodilator chemical), which is
discharge at the site of inflammation.
AGRANULOCYTE
The agranulocytes include lymphocytes and monocytes, WBCs that lack visible
cytoplasmic granules. Although they are similar structurally, they are
functionally distinct and unrelated cell types. Their nuclei are typically
spherical or kidney shaped.
Monocytes, which account for 3–8% of WBCs, have an average diameter of 18 µm and
are the largest leukocytes. They have abundant pale-blue cytoplasm and a darkly
staining purple nucleus, which is distinctively U or kidney shaped. When circulating
monocytes leave the bloodstream and enter the tissues, they differentiate into highly
mobile macrophages with prodigious appetites. Macrophages are actively phagocytic,
and they are crucial in the body’s defense against viruses, certain intracellular bacterial
parasites, and chronic infections such as tuberculosis. Macrophages are also important
in activating lymphocytes to mount the immune response.
Many of the hematopoietic hormones (EPO and several of the CSFs) are used
clinically to stimulate the bone marrow of cancer patients who are receiving
chemotherapy (which suppresses the marrow) and of those who have received marrow
transplants, and to beef up the protective responses of AIDS patients. It shows the
pathways of leukocyte differentiation. An early branching of the pathway divides the
lymphoid stem cells, which produce lymphocytes, from the myeloid stem cells, which
give rise to all other formed elements. In each granulocyte line, the committed cells,
called myeloblasts (mi′ĕ-lo-blasts″), accumulate lysosomes, becoming promyelocytes.
The distinctive granules of each granulocyte type appear next in the myelocyte stage
and then cell division stops. In the subsequent stage, the nuclei arc, producing the band
cell stage. Just before granulocytes leave the marrow and enter the circulation, their
nuclei constrict, beginning the process of nuclear segmentation. The bone marrow
stores mature granulocytes and usually contains about ten times more granulocytes
than are found in the blood. The normal ratio of granulocytes to erythrocytes produced
is about 3:1, which reflects the much shorter life span (0.5 to 9.0 days) of the
granulocytes, most of which die combating invading microorganisms.
PLATELETS
Platelets are not cells in the strict sense. About one-fourth the diameter of
a lymphocyte, they are cytoplasmic fragments of extraordinarily large cells (up to
60 µm in diameter) called megakaryocytes (meg″ah-kar′e-o-sītz). In blood smears,
each platelet exhibits a blue-staining outer region and an inner area containing
granules that stain purple. The granules contain an impressive array of chemicals
that act in the clotting process, including serotonin, Ca2+, a variety of enzymes,
ADP, and platelet-derived growth factor (PDGF). Platelets are essential for the
clotting process that occurs in plasma when blood vessels are ruptured or their
lining is injured. By sticking to the damaged site, platelets form a temporary plug
that helps seal the break. (This mechanism is explained shortly.) Because
platelets are anucleate, they age quickly and degenerate in about ten days if they
are not involved in clotting. In the meantime, they circulate freely, kept mobile but
inactive by molecules (nitric oxide, prostacyclin) secreted by endothelial cells
lining the blood vessels. Platelet formation is regulated by a hormone called
thrombopoietin. Their immediate ancestral cells, the megakaryocytes, are
progeny of the hemocytoblast and the myeloid stem cell, but their formation is
quite unusual In this line, repeated mitoses of the megakaryoblast occur, but
cytokinesis does not. The final result is the megakaryocyte (literally “big nucleus
cell”), a bizarre cell with a huge, multilobed nucleus and a large cytoplasmic
mass. When formed, the megakaryocyte presses up against a sinusoid (the
specialized type of capillary in the marrow) and sends cytoplasmic extensions
through the sinusoid wall into the bloodstream. These extensions rupture,
releasing the platelet fragments like stamps being torn from a sheet of postage
stamps and seeding the blood with platelets. The plasma membranes associated
with each fragment quickly seal around the cytoplasm to form the grainy, roughly
disc-shaped platelets, each with a diameter of 2–4 µm. Each cubic millimeter of
blood contains between 150,000 and 400,000 of the tiny platelets.
Formation of platelets
FORMATION OF BLOOD CELL
HEMOSTASIS
Normally, blood flows smoothly past the intact blood vessel lining (endothelium).
But if a blood vessel wall breaks, a whole series of reactions is set in motion to
accomplish hemostasis (he″mo-sta′sis), or stoppage of bleeding (stasis = halting).
Without this plug-the-hole defensive reaction, we would quickly bleed out our entire
blood volume from even the smallest cuts.
The hemostasis response, which is fast, localized, and carefully controlled, involves
many blood coagulation factors normally present in plasma as well as some substances
that are released by platelets and injured tissue cells. During hemostasis, three steps
occur in rapid sequence: (1) vascular spasms, (2) platelet plug formation, and (3)
coagulation, or blood clotting. Blood loss at the site is permanently prevented when
fibrous tissue grows into the clot and seals the hole in the blood vessel.
Response to Vascular Injury
VASCULAR SPASM
Platelets play a key role in hemostasis by forming a plug that temporarily seals the
break in the vessel wall. They also help to orchestrate subsequent events that lead to
blood clot formation. As a rule, platelets do not stick to each other or to the smooth
endothelial linings of blood vessels. However, when the endothelium is damaged and
underlying collagen fibers are exposed, platelets, with the help of a large plasma protein
called von Willebrand factor (VWF) synthesized by endothelial cells, adhere tenaciously
to the collagen fibers and undergo some remarkable changes. They swell, form spiked
processes, and become sticky.
Once attached, the platelets are activated and their granules begin to break down and
release several chemicals. Some, like serotonin, enhance the vascular spasm. Others,
like adenosine diphosphate (ADP), are potent aggregating agents that attract more
platelets to the area and cause them to release their contents. Thromboxane A2 (throm-
boks′ān), a short-lived prostaglandin derivative that is generated and released,
stimulates both events. Thus, a positive feedback cycle that activates and attracts
greater and greater numbers of platelets to the area begins and, within one minute, a
platelet plug is built up, which further reduces blood loss. Limiting the platelet plug to the
immediate area where it is needed is the task of prostacyclin (also called PGI2), a
prostaglandin produced by intact endothelial cells that is a strong inhibitor of platelet
aggregation. Platelet plugs are loosely knit, but when reinforced by fibrin threads to act
as a “molecular glue” for the aggregated platelets, they are quite effective in sealing the
small tears in a blood vessel that occur with normal activity. Once the platelet plug is
formed, the next stage, coagulation, comes into play.
Coagulation
A clot is not a permanent solution to blood vessel injury, and a process called
fibrinolysis removes unneeded clots when healing has occurred. Because small clots
are formed continually in vessels throughout the body, this cleanup detail is crucial.
Without fibrinolysis, blood vessels would gradually become completely blocked.
Bone marrow
Bone marrow is the flexible tissue found in the hollow interior of bones. In adults,
marrow in large bones produces new blood cells. It constitutes 4%[1] of total body
weight, i.e. approximately 2.6 kg (5.7 lbs.) in adults.
Marrow types
A femur with a cortex of cortical bone and medulla of trabecular bone showing its red
bone marrow and foci of yellow bone marrow.
There are two types of bone marrow: red marrow (consisting mainly of myeloid tissue)
and yellow marrow (consisting mainly of fat cells). Red blood cells, platelets and most
white blood cells arise in red marrow. Both types of bone marrow contain numerous
blood vessels and capillaries.
At birth, all bone marrow is red. With age, more and more of it is converted to the yellow
[1]
type. About half of adult bone marrow is red. Red marrow is found mainly in the flat
bones, such as the hip bone, breast bone, skull, ribs, vertebrae and shoulder blades,
and in the cancellous ("spongy") material at the epiphyseal ends of the long bones such
as the femur and humerus. Yellow marrow is found in the hollow interior of the middle
portion of long bones.
In cases of severe blood periods, the body can convert yellow marrow back to red
marrow to increase blood cell production.
Stroma
The stroma of the bone marrow is all tissue that isn't directly involved in the primary
function of hematopoiesis. The yellow bone marrow belongs here, and makes the
majority of the bone marrow stroma, in addition to stromal cells located in the red bone
marrow. Yellow bone marrow is found in the Medullary cavity.
Still, the stroma is indirectly involved in hematopoiesis, since it provides the
hematopoietic microenvironment that facilitates hematopoiesis by the parenchymal
cells. For instance, they generate colony stimulating factors, affecting hematopoiesis.
Macrophages contribute especially to red blood cell production. They deliver iron for
hemoglobin-production.
Hematopoietic stem cells may also cross the bone marrow barrier, and may thus be
harvested from blood.
Stem cells
The bone marrow stroma contain mesenchymal stem cells (also called marrow stromal
cells). These cells are multipotent stem cells that can differentiate into a variety of cell
types. Cell types that MSCs have been shown to differentiate into in vitro or in vivo
include osteoblasts, chondrocytes, myocytes, adipocytes, and, as described lately,
beta-pancreatic islets cells. They can also transdifferentiate into neuronal cells.
Compartmentalization
There is biologic compartmentalization in the bone marrow, in that certain cell types
tend to aggregate in specific areas. For instance, erythrocytes, macrophages and their
precursors tend to gather around blood vessels, while granulocytes gather at the
borders of the bone marrow.
• Hematopoietic stem cells give rise to the three classes of blood cells that are
found in the circulation: white blood cells (leukocytes), red blood cells
(erythrocytes), and platelets (thrombocytes).
• Mesenchymal stem cells are found arrayed around the central sinus in the bone
marrow. They have the capability to differentiate into osteoblasts, chondrocytes,
myocytes, and many other types of cells. They also function as "gatekeeper"
cells of the bone marrow.
• Endothelial stem cells
BONE MARROW
Developing neutrophils
Human, air-dried marrow smear, Wright's stain, 1416 x.
Myeloblast: The stem cell of the leucocytic series with lightly basophilic cytoplasm.
The nuclei are large and rounded. The chromatin is in the form of moderately coarse
interconnected strands. They constitute 0.3 to 0.5 per cent of marrow cells. Myeloblasts
increase in leukemia.
Neutrophilic bands: These are immature neutrophils. The nuclei are horseshoe- or
drumstick-shaped.
END