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CONNECTIVE TISSUE
Dr. Makarchuk Irina
CONNECTIVE TISSUE COMPRISES A DIVERSE GROUP
OF CELLS WITHIN A TISSUE - SPECIFIC
EXTRACELLULAR MATRIX
 In
general, connective tissue consists of cells and an
extracellular matrix (ECM).
 ECM includes structural (fibers) and specialized
proteins that constitute the ground substance.
 Connective tissue forms a vast and continuous
compartment throughout the body, bounded by the
basal laminae of the various epithelia and by the basal
or external laminae of muscle cells and nervesupporting cells.
CLASSIFICATION OF CONNECTIVE TISSUE IS BASED ON THE
COMPOSITION AND ORGANIZATION OF ITS CELLULAR AND
EXTRACELLULAR COMPONENTS AND ON ITS FUNCTIONS.
Classification of Connective Tissue
Embryonic connective tissue
Mesenchyme
Mucous connective tissue
Connective tissue proper
Loose connective tissue
Dense connective tissue
Regular
Irregular
Specialized connective tissue
Blood
Hemopoietic tissue
Adipose tissue
Lymphatic tissue
Cartilage
Bone
BLOOD IS A FLUID CONNECTIVE TISSUE THAT CIRCULATES
THROUGH THE CARDIOVASCULAR SYSTEM.
Like the other connective tissues, blood consists of cells and an
extracellular component.
Total blood volume in the average adult is about 6 L or 7% to 8% of
total body weight.
The heart’s pumping action propels blood through the cardiovascular
system to the body tissues.
Blood’s many functions include:
 delivery of nutrients and oxygen directly or indirectly to cells,
 transport of wastes and carbon dioxide away from cells,
 delivery of hormones and other regulatory substances to and from
cells and tissues,
 maintenance of homeostasis by acting as a buffer and participating in
coagulation and thermoregulation, and
 transport of humoral agents and cells of the immune system that
protect the body from pathogenic agents, foreign proteins, and
transformed cells (i.e., cancer cells).
BLOOD CONSISTS OF CELLS AND THEIR DERIVATIVES
AND A PROTEIN RICH FLUID CALLED PLASMA.
Blood cells and their derivatives include:
• erythrocytes, also called red blood cells
(RBCs),
 • leukocytes, also known as white blood
cells (WBCs), and
 • thrombocytes, also termed platelets.
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PLASMA IS THE LIQUID EXTRACELLULAR MATERIAL THAT
IMPARTS FLUID PROPERTIES TO BLOOD.
The relative volume of cells and plasma in whole blood is
approximately 45% and 55%, respectively. The volume of packed
erythrocytes in a sample of blood is called the hematocrit.
N.B. ! The hematocrit is measured by centrifuging a blood
sample to which anticoagulants have been added, and
then calculating the percentage of the centrifuge tube
volume occupied by the erythrocytes compared with that
of the whole blood.
 A normal hematocrit reading is about 39% to 50% in men and
35% to 45% in women; thus, 39% to 50% and 35% to 45% of the
blood volume for men and women, respectively, consists of
erythrocytes.
 Low hematocrit values often reflect reduced numbers of
circulating erythrocytes (a condition called anemia) and may
indicate significant blood loss caused by internal or external
bleeding.

COMPOSITION OF BLOOD PLASMA
FORMED ELEMENTS OF THE BLOOD
ERYTHROCYTES
Erythrocytes or red blood cells (RBCs), are anucleate cells devoid of typical
organelles. They function only within the bloodstream to bind oxygen for
delivery to the tissues and, in exchange, bind carbon dioxide for removal from
the tissues. Their shape is that of a biconcave discs with a diameter of 7.8 µm,
an edge thickness of 2.6 µm, and a central thickness of 0.8 µm. This shape
maximizes the cell’s surface area (140 µm2), an important attribute in gas
exchange.
N.B.! The life span of erythrocytes is approximately 120 days, after
which most (90%) of them are phagocytosed by macrophages in the
spleen, bone marrow, and liver. The remaining aged erythrocytes
(10%) break down intravascularly, releasing insignificant amounts of
hemoglobin into the blood.
Erythrocytes contain
hemoglobin, a protein
specialized for the transport
of oxygen and carbon
dioxide.
HEMOGLOBIN
consists of four polypeptide chains of globin α, β, δ and γ, each
complexed to an iron-containing heme group. The structure of the
polypeptide chains varies. Depending on the particular polypeptides
present, the following types of hemoglobin can be distinguished:
 Hemoglobin HbA is most prevalent in adults, accounting for about
96% of total hemoglobin. It is a tetramer with two α and two β chains
(α2β2).
 Hemoglobin HbA2 accounts for 1.5% to 3% of total hemoglobin in
adults. It consists of two α and two δ chains (α2δ2).
 Hemoglobin HbF accounts for less than 1% of total hemoglobin in
adults. It contains two α and two δ chains (α2δ2) and is the principal
form of hemoglobin in the fetus.
N.B.! HbF production falls dramatically after birth; however, in some
individuals HbF is produced throughout their entire lives. Although HbF
persists in slightly higher percentages than normal in those with sickle
cell disease and thalassemia, it does not appear to have a pathologic
role.
LEUKOCYTES
Leukocytes are subclassified into two general groups. The basis
for this division is the presence or absence of prominent
specific granules in the cytoplasm.
As previously noted, cells containing specific granules are
classified as granulocytes (neutrophils, eosinophils, and
basophils), and cells that lack specific granules are classified as
agranulocytes (lymphocytes and monocytes).
However, both agranulocytes and granulocytes possess small
number of nonspecific azurophilic granules, which are
lysosomes.
NEUTROPHILS
Neutrophils measure 10 to 12 µm in
diameter in blood smears and are
obviously larger than erythrocytes.
Although named for their lack of
characteristic cytoplasmic staining,
they are also readily identified by their
multilobal nucleus; thus, they are also
called polymorphonuclear
neutrophils or polymorphs.
Neutrophils are motile cells; they leave
the circulation and migrate to their site
of action in the connective tissue.
Neutrophils are active phagocytes that
utilize a variety of surface receptors to
recognize bacteria and other infectious
agents at the site of inflammation.
NEUTROPHIL PHAGOCYTOSIS
 Phagocytosed bacteria are killed within phagolysosomes by the toxic
reactive oxygen intermediates produced during respiratory burst.
 Phagocytosed bacteria can also be killed by a diverse arsenal of
oxygen-independent killing mechanisms utilizing bacteriolytic
enzymes and antimicrobial peptides.
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The cytoplasm of a neutrophil contains three kinds of
granules. The different types of granules reflect the various
phagocytotic functions of the cell.
Specific granules (secondary granules) are the smallest
granules and are at least twice as numerous as azurophilic
granules. They are barely visible in the light microscope; in electron
micrographs, they are ellipsoidal. Specific granules contain various
enzymes as well as complement activators and other antimicrobial
peptides.
Azurophilic granules (primary granules) are larger and less
numerous than specific granules. They arise early in granulopoiesis
and occur in all granulocytes, as well as in monocytes and
lymphocytes. The azurophilic granules are the lysosomes of the
neutrophil and contain myeloperoxidase (MPO) (a peroxidase
enzyme). Myeloperoxidase helps to generate highly reactive
bactericidal hypochlorite and chloramines.
Tertiary granules in neutrophils are of two types. One type
contains phosphatases (enzymes that remove a phosphate group
from a substrate) and is sometimes called a phosphasome. The
other type contains metalloproteinases, such as gelatinases and
collagenases, which are thought to facilitate the migration of the
neutrophil through the connective tissue.
EOSINOPHILS
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Eosinophils are about the same size as neutrophils, and their nuclei are
typically bilobed.
Eosinophils are named for the large, eosinophilic, refractile granules in
their cytoplasm.
The cytoplasm of eosinophils contains two types of granules: numerous,
large, elongated specific granules and azurophilic granules.
Eosinophils are associated with allergic
reactions, parasitic infections,
and chronic inflammation.
Eosinophils develop and mature in the
bone marrow. Once released from the
bone marrow, they circulate in peripheral
blood and then migrate to the connective
tissue. Eosinophils are activated by
interactions with IgG, IgA, or
secretory IgA antibodies.
BASOPHILS
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Basophils are about the same size
as neutrophils and are so named
because the numerous large
granules in their cytoplasm stain
with basic dyes
Often, several hundred WBCs must
be examined in a blood smear
before one basophil is found.
Basophils are the least numerous of
the WBCs, accounting for less than
0.5% of total leukocytes.
The basophil cytoplasm contains
two types of granules: specific
granules, which are larger than the
specific granules of the neutrophil,
and nonspecific azurophilic
granules.
LYMPHOCYTES
Lymphocytes are the main
functional cells of the lymphatic
or immune system.
 Lymphocytes are the most
common agranulocytes and
account for about 30% of the
total blood leukocytes.
 In blood smears, the mature
lymphocyte approximates the
size of an erythrocyte.
 Three functionally distinct types
of lymphocytes are present in
the body: T lymphocytes, B
lymphocytes, and Natural killer
(NK) cells.

THE CHARACTERIZATION OF LYMPHOCYTE TYPES IS BASED ON
THEIR FUNCTION, NOT ON THEIR SIZE OR MORPHOLOGY.
T lymphocytes (T cells) are so named because they undergo
differentiation in the thymus. Several different types of T
lymphocytes have been identified: cytotoxic, helper, suppressor,
and gamma/delta (γ/δ).
 B lymphocytes (B cells) are so named because they were first
recognized as a separate population in the bursa of Fabricius in
birds or bursa-equivalent organs (e.g., bone marrow) in
mammals.
 Natural killer (NK) cells develop from the same precursor cell
as B and T cells and are so named because they are
programmed to kill certain types of transformed cells.
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MONOCYTES
 Monocytes are the precursors of the cells of the mononuclear
phagocytotic system. Monocytes are the largest of the WBCs
in a blood smear (average diameter, 18 µm).
They travel from the bone marrow to the
body tissues, where they differentiate
into the various phagocytes of the
mononuclear phagocytotic system —
that is, connective tissue macrophages,
osteoclasts, alveolar macrophages,
perisinusoidal macrophages in the liver
(Kupffer cells), and macrophages of
lymph nodes, spleen, and bone marrow
among others.
Monocytes remain in the blood for only about 3 days.
Monocytes transform into macrophages, which function as antigen-presenting cells
in the immune system.
During inflammation, the monocyte leaves the blood vessel at the site of
inflammation, transforms into a tissue macrophage, and phagocytoses bacteria, other
cells, and tissue debris.
THROMBOCYTES
Thrombocytes are small, membrane-bounded, anucleate
cytoplasmic fragments derived from megakaryocytes.
 Thrombocytes (platelets) are derived from large polyploid cells
(cells whose nuclei contain multiple sets of chromosomes) in
the bone marrow called megakaryocytes.
 After entry into the vascular system from the bone marrow, the
platelets circulate as discoid structures about 2 to 3 m in
diameter.
 Their life span is about 10 days.
 Structurally, platelets may be divided into four zones based on
organization and function:
 The peripheral zone
 The structural zone
 The organelle zone
 The membrane zone
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Platelets function in continuous surveillance of blood
vessels, blood clot formation, and repair of injured tissue.
FORMATION OF BLOOD CELLS (HEMOPOIESIS)
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Hemopoiesis (hematopoiesis) includes both erythropoiesis and
leukopoiesis (development of red and white blood cells,
respectively), as well as thrombopoiesis (development of platelets).
Blood cells have a limited life span; they are continuously produced
and destroyed. The ultimate objective of hemopoiesis is to maintain
a constant level of the different cell types found in the peripheral
blood.
Both the human erythrocyte (life span of 120 days) and the platelet
(life span of 10 days) spend their entire life in the circulating blood.
Leukocytes, however, migrate out of the circulation shortly after
entering it from the bone marrow and spend most of their variable
life spans (and perform all of their functions) in the tissues.
In the adult, erythrocytes, granulocytes, monocytes, and platelets are
formed in the red bone marrow; lymphocytes are also formed in the
red bone marrow and in the lymphatic tissues.
Hemopoiesis.
This chart is based on the most
recent concepts in
hemopoiesis. It shows blood
cells’ development from
hemopoietic stem cells in the
bone marrow to mature cells
and their distribution in the
blood and connective tissue
compartments.
In all lineages, extensive
proliferation occurs during
differentiation. Cytokines
(including hemopoietic growth
factors) may and do act
individually and severally at
any point in the process from
the first stem cell to the
mature blood or connective
tissue cell.
Stages of erythrocytic
and granular leukocytic
differentiation with
Romanovsky type
stain. Shown here are
normal human bone
marrow cells as they
would typically appear
in a smear.
CONNECTIVE TISSUE PROPER
Connective tissues that belong to this category are divided into
two general subtypes:
 Loose connective tissue, sometimes called areolar tissue, and
 Dense connective tissue, which can be further subcategorized
into two basic types based on the organization of its collagen
fibers: dense irregular connective tissue and dense regular
connective tissue.
LOOSE CONNECTIVE TISSUE
is characterized by loosely arranged fibers and abundant cells
of various types.
 is a cellular connective tissue with thin and relatively sparse
collagen fibers.
 is the site of inflammatory and immune reactions. During these
reactions, loose connective tissue can swell considerably. In
areas of the body where foreign substances are continually
present, large populations of immune cells are maintained. For
example, the lamina propria, the loose connective tissue of
mucous membranes, such as those of the respiratory and
alimentary systems, contains large numbers of these cells.
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DENSE IRREGULAR CONNECTIVE TISSUE
is characterized by abundant fibers and few cells.
 contains mostly collagen fibers. Cells are sparse and are
typically of a single type, the fibroblast. This tissue also contains
relatively little ground substance.
 Because of its high proportion of collagen fibers, dense irregular
connective tissue provides significant strength.
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DENSE REGULAR CONNECTIVE TISSUE
is characterized by ordered and densely packed arrays of fibers
and cells.
 Dense regular connective tissue is the main functional
component of tendons, ligaments, and aponeuroses.
 the fibers are arranged in parallel array and are densely packed
to provide maximum strength. The cells that produce and
maintain the fibers are packed and aligned between fiber
bundles.
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CONNECTIVE TISSUE FIBERS
Connective tissue fibers are of three principal
types.
 Connective tissue fibers are present in varying
amounts, depending on the structural needs or function
of the connective tissue. Each type of fiber is produced
by fibroblasts and is composed of protein consisting of
long peptide chains. The types of connective tissue
fibers are:
 Collagen fibers
 Reticular fibers
 Elastic fibers
CONNECTIVE TISSUE CELLS
Connective tissue cells can be resident or wandering. The cells that make up the
resident cell population are relatively stable; they typically exhibit little
movement and can be regarded as permanent residents of the tissue. These
resident cells include:
•fibroblasts and a closely related cell type, the myofibroblast,
• macrophages,
• adipocytes,
• mast cells, and
• adult stem cells.
The wandering cell population or transient cell population consists primarily of
cells that have migrated into the tissue from the blood in response to specific
stimuli. These include:
• lymphocytes,
• plasma cells,
• neutrophils,
• eosinophils,
• basophils, and
• monocytes.