ANATOMY AND PHYSIOLOGY OF BLOOD

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.

Blood is sticky opaque fluid within a characteristic metallic taste. As children, we

discover its saltiness the first time we stick a cut finger into our mouth. The color of the
blood is depending on its oxygen content. A scarlet blood color indicates rich amount of
oxygen, while dull-red indicates poor oxygen supply. Blood it much thicker than water
and about five times thicker, it is due to its formed content. Blood is slightly alkaline,
about 7.35-7.45 ph. Its temperature is about 38 degree Celsius, and much warmer than
body temperature. Blood accounts for approximately eight percent of the body’s weight,
and its volume in healthy males is five to six liters.

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.)

Regulation: maintaining appropriate body temperature by absorbing and distributing

heat throughout the body and to the skin surface to encourage heat loss. It also
maintains normal PH in body tissues. Many blood proteins and other bloodborne solutes
act as buffer to prevent excessive or abrupt changes in blood pH that could jeopardize
normal cell activities. Additionally, blood acts as the reservoir for the body’s alkaline
reserve of bicarbonates atom. Maintaining adequate fluid volume in the circulatory
system.

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

Constituent Major function

Water Solvent for carrying other substances;
absorbs heat.

Salts (Electrolytes)
•Sodium Osmotic balance.
•Potassium pH buffering, regulation of membrane
•Calcium permeability.
•Magnesium
•Chloride
•Bicarbonate.

Plasma Proteins

•Albumin Osmotic balance, pH buffering

•Fibrinogen Clotting of blood

•Globulins Defense (antibodies) and lipid transport.

 ERYTHROCYTES

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.

The erythrocytes are superb example of complementarities of structure and

function. It picks oxygen in the capillary beds of the lungs and releases it to tissue cells
across other capillaries throughout the body, it also transport 20% of the carbon dioxide
released by the tissue cells back to the lung.

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

Blood cell formation is referred to as hemotopoiesis, or hemopoiesis. This

process occurs in the red bone marrow, which is composed of largely soft network of
reticular connective tissue bordering on wide blood capillaries called blood sinusoids.
Within this network are immature blood cells, macrophages, fat cells, and reticular cell.
In adults, red bone marrow is found chiefly in the bones axial skeleton and girdles, and
in the proximal epiphyses of the humerus and femur. Each type of blood cell is
produced in different numbers in response changing blood need and regulatory factors.
As they mature, they migrate through the thin walls of the sinusoids to enter the
bloodstream. On average, the marrow turns out an ounce of new of new blood,
containing 100 billion new cells each and every day. All blood cell has different function
and structure, but they came from one single cell which is the mother stem cell. As they
are produces, they are being trained to do their own function and specializations.
 Erythrocytes production, or erythropoiesis begins when a hemocytoblast
descendant called a myeloid stem cells is transformed into a proerythroblast , in turn,
give rises to the early erythroblast that produce huge number of ribosomes. During
these first two phases, the cells divide many times. Hemoglobin synthesis and iron
accumulation occur as the early erythroblast is transformed into a late erythroblast and
then normoblast.the color of the cell cytoplasm change blue when ribosomes become
mask of by the pink color hemoglobin, it ejects most of its organelles. Its nucleus
function and purpose degenerates and pinched off, allowing the cell to collapse inward
assumed the biconcave shape. The result of it is reticulocyte, so named because it is
still contains a scant of reticulum of clumped ribosomes. The entire process from
hemocytoblast to reticulocyte takes about 15 days. The reticulocytes, filled with burst
hemoglobin, enter bloodstream to begin their task of oxygen transport. Usually they
become fully mature RBC within two days of release as their ribosomes degraded by
reticular enzyme. Reticulocytes account 1-2% of all RBC in the blood of healthy people.
Reticulocyte counts provided rough index of the rate of RBC formation-reticulocyte
counts below or above this percentage range indicate abnormal rates of RBC formation.

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

granulocyte, which include neutrophils, basophils, and eosinophils, are all

roughly spherical in shape. They are larger and much shorter lived than RBC. They
characteristically have lobed nuclei, and their membrane-bound cytoplasmic granules
stain quite specifically with Wright’s stain. Functionally, all granulocytes are phagocytes
to a greater or lesser degree.
 NEUTROPHILS

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.

• contains fine granules

• a 3-6 lobed nucleus
 EOSINOPHILS

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.

• large course granules

• bi-lobed nucleus
 BASOPHILS

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.

Lymphocytes Lymphocytes, accounting for 25% or more of the WBC

population, are the second most numerous leukocytes in the blood. When
stained, a typical lymphocyte has a large, dark-purple nucleus that occupies
most of the cell volume. The nucleus is usually spherical but may be slightly
indented, and it is surrounded by a thin rim of pale-blue cytoplasm.
Lymphocyte diameter ranges from 5 to 17 µm, but they are often classified
according to size as small (5–8 µm), medium (10–12 µm), and large (14–17
µm).
Although large numbers of lymphocytes exist in the body, only a small
proportion of them (mostly the small lymphocytes) is found in the
bloodstream. In fact, lymphocytes are so called because most are firmly
enmeshed in lymphoid tissues (lymph nodes, spleen, etc.), where they play a
crucial role in immunity. T lymphocytes (T cells) function in the immune
response by acting directly against virus-infected cells and tumor cells. B
lymphocytes (B cells) give rise to plasma cells, which produce antibodies
(immunoglobulins) that are released to the blood.

Large dark spherical nucleus

i). T-lymphocytes (T-cells)

ii). B-lymphocytes (B-cells)

 MONOCYTES

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.

LARGEST LEUKOCYTES / U- SHAPE NUCLEUS

Production and Life Span of Leukocytes
Like erythropoiesis, leukopoiesis, or the production of white blood cells, is
stimulated by chemical messengers. These messengers, which can act
either as paracrines or hormones, are glycoproteins that fall into two
families of hematopoietic factors, interleukins and colony-stimulating
factors, or CSFs. The interleukins are numbered (e.g., IL-3, IL-5), whereas
most CSFs are named for the leukocyte population they stimulate—thus
granulocyte-CSF (G-CSF) stimulates production of granulocytes.
Hematopoietic factors, released by supporting cells of the bone marrow and
mature WBCs, not only prompt the white blood cell precursors to divide and
mature, but also enhance the protective potency of mature leukocytes.

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.

Despite their similar appearances, the two types of agranulocytes have

very different lineages. Monocytes diverge from a myeloblast that can become
either a neutrophil or a monocyte. Cells following the monocyte line pass through
the promonocyte stage before leaving the bone marrow and becoming
monocytes. Lymphocytes derive from the lymphoid stem cell and progress
through the lymphoblast and prolymphocyte stages. The prolymphocytes leave
the bone marrow and travel to the lymphoid tissues, where their further
differentiation occurs. Monocytes may live for several months, whereas the life
span of lymphocytes varies from a few days to decades.

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

The immediate response to blood vessel injury is constriction of the damaged

blood vessel (vasoconstriction). Factors that trigger this vascular spasm include direct
injury to vascular smooth muscle, chemicals released by endothelial cells and platelets,
and reflexes initiated by local pain receptors. The spasm mechanism becomes more
and more efficient as the amount of tissue damage increases, and is most effective in
the smaller blood vessels. The value of the spasm response is obvious: A strongly
constricted artery can significantly reduce blood loss for 20–30 minutes, allowing time
for platelet plug formation and blood clotting to occur.
 PLATELET PLUG FORMATION

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

Coagulation or blood clotting, during which blood is transformed from a liquid to a

gel, is a multistep process that leads to its critically important last three phases:
• A complex substance called prothrombin activator is formed.
• Prothrombin activator converts a plasma protein called prothrombin into
thrombin, an enzyme.
 • Thrombin catalyzes the joining of fibrinogen molecules present in plasma to a
fibrin mesh, which traps blood cells and effectively seals the hole until the blood
vessel can be permanently repaired.

The complete coagulation process is much more complicated, however. Over 30

different substances are involved. Factors that enhance clot formation are called clotting
factors or procoagulants. Although vitamin K is not directly involved in coagulation, this
fat-soluble vitamin is required for the synthesis of four of the procoagulants made by the
liver. Factors that inhibit clotting are called anticoagulants. Whether or not blood clots
depends on a delicate balance between these two groups of factors. Normally,
anticoagulants dominate and clotting is prevented; but when a vessel is ruptured,
procoagulant activity in that area increases dramatically and clot formation begins. The
procoagulants are numbered I to XIII according to the order of their discovery; hence
the numerical order does not reflect the reaction sequence. Tissue factor (III) and Ca2+
(IV) are usually indicated by their names, rather than by numerals. Most of these factors
are plasma proteins made by the liver that circulate in an inactive form in blood until
mobilized.

Clot Retraction and Repair

Within 30 to 60 minutes, the clot is stabilized further by a platelet-induced

process called clot retraction. Platelets contain contractile proteins (actin and myosin),
and they contract in much the same manner as muscle cells. As the platelets contract,
they pull on the surrounding fibrin strands, squeezing serum (plasma minus the clotting
proteins) from the mass, compacting the clot and drawing the ruptured edges of the
blood vessel more closely together. Even as clot retraction is occurring, vessel healing
is taking place. Platelet-derived growth factor (PDGF) released by platelet degranulation
stimulates smooth muscle cells and fibroblasts to divide and rebuild the wall. As
fibroblasts form a connective tissue patch in the injured area, endothelial cells,
stimulated by vascular endothelial growth factor (VEGF), multiply and restore the
endothelial lining.
 Fibrinolysis

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.

ANATOMY OF BONE MARROW

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.

Cells that constitute the bone marrow stroma are:

• fibroblasts (reticular connective tissue)

• macrophages
• adipocytes
• osteoblasts
• osteoclasts
• endothelial cells forming the sinusoids

Macrophages contribute especially to red blood cell production. They deliver iron for
hemoglobin-production.

Bone marrow barrier

The blood vessels constitute a barrier, inhibiting immature blood cells from leaving the
bone marrow. Only mature blood cells contain the membrane proteins required to attach
to and pass the blood vessel endothelium.

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.

Types of stem cells

Bone marrow contains three types of stem cells:[2]

• 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.

Progranulocyte: Also called promyelocyte. It arises and differentiates from

myeloblasts. It has large cells; its nuclei are rounded with coarse chromatin. Cytoplasm
is basophilic with some azurophilic granules. This cell type constitutes about 4 per cent
of marrow cells.

Neutrophilic myelocyte: This arises from progranulocytes. It is smaller, has less

basophilic cytoplasm containing differentiated granules and a nucleus with more
compact chromatin.

Neutrophilic bands: These are immature neutrophils. The nuclei are horseshoe- or
drumstick-shaped.

Neutrophilic metamyelocyte: It has a kidney-shaped nucleus and is not capable of

division. It differentiates into mature neutrophilic myelocytes.
Neutrophil (segmented): This is a mature cell. Its nucleus is markedly lobulated. The
lobules may be connected with a thin chromatin thread. Chromatin is compact, and
there is abundant cytoplasm. Granules in the cytoplasm are small and may be
inconspicuous.
BONE MARROW

END