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Dr. Emad I H Shaqoura
M.D, M.Sc. Anatomy
Faculty of Medicine, Islamic University-Gaza
October, 2015
Connective Tissue
Functions of the Connective Tissue
1. Maintains the form of organs throughout the body.
2. Provides a matrix that supports and binds other tissues and
cells together in organs.
3. The interstitial fluid of connective tissue gives metabolic
support to cells as the medium for diffusion of nutrients
and waste products.
4. Aiding in the defense and protection of the body.
5. Storage of fat.
Connective Tissue, Dr. Emad I Shaqoura, IUG 2
Structure of the Connective Tissue
It is the most abundant of the four basic tissue types.
Connective Tissue
Extracellular Matrix
Fibers Ground
Substance
Cells
Connective Tissue, Dr. Emad I Shaqoura, IUG 3
Structure of the Connective Tissue
The connective tissue is composed of:
1. Cells.
2. Extracellular matrix.
It is the major constituent of the connective tissue.
It is composed of:
1. Protein fibers: (collagen, reticular, and elastic)
2. Ground substance: anionic hydrophilic mixture of
proteoglycans, GAGs and multiadhesive glycoproteins.
Connective Tissue, Dr. Emad I Shaqoura, IUG 4
Copyright © McGraw-Hill Companies
Figure 5-2
Embryonic Origin of C.T
Connective tissues originate from embryonic mesenchyme ,
a tissue developing mainly from the mesoderm.
Mesenchyme consists largely of viscous ground substance
with few collagen fibers and cells.
Mesenchymal cells are undifferentiated, spindle-shaped cells.
They have:
1. large nuclei, with prominent nucleoli and fine chromatin.
2. Scant cytoplasm extended as two or more thin cytoplasmic
processes.
Connective Tissue, Dr. Emad I Shaqoura, IUG 6
Copyright © McGraw-Hill Companies
Figure 5-1
Embryonic Origin of C.T (cont’d)
Mesodermal cells migrate from their origin, surround and
penetrate developing organs.
Embryonic mesenchyme:
1. Produces all types of connective tissue proper and the
specialized connective tissues.
2. Includes stem cells for other tissues such as blood, the
vascular endothelium, and muscle.
Connective Tissue, Dr. Emad I Shaqoura, IUG 8
Cells of Connective Tissue
© Elsevier. Gartner & Hiatt: Color Textbook of Histology 3E. Connective Tissue, Dr. Emad I Shaqoura, IUG 9
Cells of Connective Tissue (cont’d) The cells in connective tissues are grouped into two
categories: fixed cells and transient cells.
I. Fixed cells are a resident population of cells that have developed and remain in place within the connective tissue, where they perform their functions. The fixed cells are a stable and long-lived population that includes:
1. Fibroblasts
2. Adipose cells
3. Pericytes
4. Mast cells
5. Macrophages
Connective Tissue, Dr. Emad I Shaqoura, IUG 10
Cells of Connective Tissue (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 11
Cells of Connective Tissue (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 12
II. Transient cells (free or wandering cells) originate mainly in the bone marrow and circulate in the bloodstream. Upon receiving the proper stimulus or signal, these cells leave the bloodstream and migrate into the connective tissue to perform their specific functions. Because most of these motile cells are usually short-lived, they must be replaced continually from a large population of stem cells.
1. Plasma cells
2. Lymphocytes
3. Neutrophils
4. Eosinophils
5. Basophils
6. Monocytes
7. Macrophages
13
Fibroblasts
Connective Tissue, Dr. Emad I Shaqoura, IUG 14
Fibroblasts, the most common cells in connective tissue,
produce and maintain most of the tissue’s extracellular
components e.g., collagen, elastin, proteoglycans, GAGs,…..
Two levels of fibroblast activity can be observed
histologically:
1. Fibroblasts (active cells).
2. Fibrocytes (quiescent cells).
Active Fibroblast
Connective Tissue, Dr. Emad I Shaqoura, IUG 15
Has more abundant and irregularly branched cytoplasm.
Its nucleus is large, ovoid, euchromatic, and has a prominent nucleolus.
The cytoplasm has much rough endoplasmic reticulum (RER) and a well-developed Golgi apparatus.
Junqueira's Basic Histology Text and Atlas 13th Ed
Active Fibroblast (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 16
Quiescent Fibroblast
Connective Tissue, Dr. Emad I Shaqoura, IUG 17
Smaller than the active
fibroblast.
Is usually spindle-shaped
with fewer processes.
Much less RER.
Contains a darker, more
heterochromatic nucleus.
Junqueira's Basic Histology Text and Atlas 13th ed.
Fibroblasts (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 18
Fibroblasts are targets of growth factors that influence cell growth and differentiation.
In adults, connective tissue fibroblasts rarely undergo division. However, stimulated by locally released growth factors, cell cycling and mitotic activity resume when the tissue requires additional fibroblasts, for example, to repair a damaged organ.
Fibroblasts involved in wound healing, sometimes called myofibroblasts, have a well-developed contractile function and are enriched with a form of actin also found in smooth muscle cells.
Medical Application
Connective Tissue, Dr. Emad I Shaqoura, IUG 19
The regenerative capacity of connective tissue is clearly observed in organs
damaged by ischemia, inflammation, or traumatic injury.
Spaces left after such injuries, especially in tissues whose cells divide poorly or
not at all (e.g., cardiac muscle), are filled by connective tissue, forming dense
irregular scar tissue.
The healing of surgical incisions and other wounds depends on the reparative
capacity of connective tissue, particularly on activity and growth of fibroblasts.
in some rapidly closing wounds, a cell called the myofibroblast, with features of
both fibroblasts and smooth muscle cells, is also observed.
These cells have most of the morphologic characteristics of fibroblasts but
contain increased amounts of actin microfilaments and myosin and behave
much like smooth muscle cells.
Their activity is important for the phase of tissue repair called wound
contraction.
Adipocytes (Fat Cells)
Connective Tissue, Dr. Emad I Shaqoura, IUG 20
They are C.T cells
specialized for cytoplasmic
storage of lipid as neutral
fats, or less commonly for
the production of heat.
The large deposits of fat in
the cells of adipose
connective tissue also serve
to cushion and insulate the
skin and other organs.
Junqueira's Basic Histology Text and Atlas 13th ed.
Macrophages & the Mononuclear
Phagocyte System
Connective Tissue, Dr. Emad I Shaqoura, IUG 21
Macrophages are phagocytic cells specialized in turnover of protein fibers and removal of dead cells, tissue debris, or other particulate material.
Their morphology varies according to their functional activity and to the tissue they inhabit.
A typical macrophage measures between 10 and 30 μm in diameter and has an eccentrically located, oval or kidney-shaped nucleus.
Macrophages are present in the connective tissue of most organs and are often referred to by pathologists as “histiocytes.”
Macrophages & the Mononuclear
Phagocyte System (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 22
In the TEM, macrophages have a characteristic irregular
surface with pleats, protrusions, and indentations, a
morphologic expression of their active pinocytotic
and phagocytic activities.
They generally have a well-developed Golgi apparatus and
many lysosomes.
Copyright © McGraw-Hill Companies
Figure 5-4
Macrophages & the Mononuclear
Phagocyte System (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 24
Macrophages derive from bone marrow precursor cells that
divide, producing monocytes that circulate in the blood.
These cells cross the wall of venules to penetrate connective
tissue, where they differentiate further, mature, and acquire
the morphologic features of phagocytic cells.
Therefore, monocytes and macrophages are the same cell at
different stages of maturation.
Precursor Cells (bone marrow)
Monocytes (blood)
Macrophages (C.T)
Macrophages & the Mononuclear
Phagocyte System (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 25
Macrophages play an important role in the early stages of
repair after tissue damage, where they accumulate in
connective tissue by local proliferation and monocyte
recruitment from the blood.
Macrophages are distributed throughout the body.
Along with other monocyte-derived cells, they comprise a
family of cells called the mononuclear phagocyte
system.
Macrophages & the Mononuclear
Phagocyte System (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 26
Macrophages & the Mononuclear
Phagocyte System (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 27
All monocyte-derived cells are long-living cells and may
survive for months in the tissues.
The transformation from monocytes to macrophages in
connective tissue involves:
1. increases in cell size,
2. increased protein synthesis,
3. increases in the number of Golgi complexes
4. and increases in the number of lysosomes.
Medical Application
Connective Tissue, Dr. Emad I Shaqoura, IUG 28
Macrophages are key components of the innate immunity, removing cell debris, neoplastic cells, bacteria, and other invaders.
Macrophages are also important antigen-presenting cells required for the activation and specification of lymphocytes.
When macrophages are stimulated (by injection of foreign substances or by infection), they become activated macrophages, showing:
1. An increase in their capacity for phagocytosis and intracellular digestion.
2. Enhanced metabolic and lysosomal enzyme activity.
Medical Application (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 29
Macrophages are also secretory cells producing enzymes for
ECM breakdown and various growth factors or cytokines
that help regulate immune cells and reparative functions.
When adequately stimulated, macrophages may increase in
size and fuse to form multinuclear giant cells, usually
found only in pathologic conditions.
Medical Application (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 30
www.ebi.edu.au
Mast Cells
Connective Tissue, Dr. Emad I Shaqoura, IUG 31
Mast cells are oval or
irregularly shaped
connective tissue cells.
The cytoplasm is filled
with basophilic secretory
granules.
The nucleus is centrally
situated and often obscured
by abundant secretory
granules. Junqueira's Basic Histology Text and Atlas 13th ed.
Mast Cells (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 32
These granules are electron-dense and heterogeneous
(ranging from 0.3 to 2.0 μm in diameter).
Junqueira's Basic Histology Text and Atlas 13th ed.
Mast Cells (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 33
Because of their high content of acidic radicals in their
sulfated GAGs, mast cell granules display metachromasia,
which means that they can change the color of some basic
dyes (e.g., toluidine blue) from blue to purple or red.
The granules are poorly preserved by common fixatives, so
that mast cells are frequently difficult to identify.
Mast Cells (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 34
Wheater's Functional Histology - A Text and Color Atlas 6th ed.
Connective Tissue, Dr. Emad I Shaqoura, IUG 35
Wheater's Functional Histology - A Text and Color Atlas 6th ed.
Mast Cells (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 36
Progenitor cell (Bone marrow)
Progenitor cell
(Blood)
Connective tissue
Differentiate into mast cells
Mast Cells (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 37
Mast cells have roles in the local inflammatory response, innate immunity, and tissue repair through releasing important molecules such as:
1. Heparin: acts locally as an anticoagulant.
2. Histamine: which promotes increased vascular permeability and smooth muscle contraction.
3. Serine proteases: which activate various mediators of inflammation.
4. Eosinophil and neutrophil chemotactic factors: which attract those leukocytes.
5. Cytokines: polypeptides directing activities of leukocytes and other cells of the immune system.
6. Phospholipid precursors: for conversion to prostaglandins, leukotrienes, and other important lipid mediators of the inflammatory response.
Copyright © McGraw-Hill Companies
Figure 5-6
Plasma Cells
Connective Tissue, Dr. Emad I Shaqoura, IUG 39
Plasma cells are B-lymphocyte–derived, antibody-producing cells.
They are large, ovoid cells having basophilic cytoplasm due to their
richness in RER.
Next to the nucleus, the Golgi apparatus and centrioles occupy a region
that may appear pale in routine histologic preparations.
The nucleus of the plasma cell is generally spherical but eccentrically
placed.
Many of these nuclei contain compact, peripheral regions of
heterochromatin alternating with lighter areas of euchromatin, a
configuration that can give the nucleus of a plasma cell the appearance of
a clock face.
There are at least a few plasma cells in most connective tissues.
Their average lifespan is only 10-20 days.
Copyright © McGraw-Hill Companies
Figure 5-7
Medical Application Plasma cells are derived from B lymphocytes and are
responsible for the synthesis of immunoglobulin antibodies.
Each antibody is specific for the one antigen that stimulated the clone of B cells and reacts only with that antigen or molecules resembling it.
The results of the antibody-antigen reaction are variable, but they usually neutralize harmful effects caused by antigens.
An antigen that is a toxin (e.g., tetanus, diphtheria) may lose its capacity to do harm when it binds to its specific antibody.
Bound antigen-antibody complexes are quickly removed from tissues by phagocytosis.
Leukocytes
Connective Tissue, Dr. Emad I Shaqoura, IUG 42
Leukocytes, or white blood cells, make up a population of
wandering cells in connective tissue.
They leave blood by migrating between the endothelial cells
lining venules to enter connective tissue by a process called
diapedesis.
This process increases greatly during inflammation.
Fibers
Connective Tissue, Dr. Emad I Shaqoura, IUG 43
The fibrous components of connective tissue are elongated
structures formed from proteins that polymerize after
secretion from fibroblasts.
Types of fibers:
1. Collagen fibers.
2. Reticular fibers.
3. Elastic fibers: formed by elastin protein.
These fibers are distributed unequally among the different
types of connective tissue.
formed by collagen protein family
Collagen
Connective Tissue, Dr. Emad I Shaqoura, IUG 44
Collagen is the most abundant protein in the human body,
representing 30% of its dry weight.
Collagen is a key element of all connective tissues, as well as
epithelial basement membranes and the external laminae of
muscle and nerve cells.
Collagens are secreted by fibroblasts and several other cell
types.
A family of 28 collagens exists in vertebrates that can be
grouped into different categories according to the structures
formed by their interacting subunits.
Collagen Types
Connective Tissue, Dr. Emad I Shaqoura, IUG 45
1. Fibrillar collagens:
Notably collagen types I, II, and III, have subunits that
aggregate to form large fibrils clearly visible in the electron or
light microscope.
Collagen type I, the most abundant and widely distributed
collagen, forms large, eosinophilic bundles usually called
collagen fibers.
These often densely fill the connective tissue, forming
structures such as tendons, organ capsules, and dermis.
Copyright © McGraw-Hill Companies
Figure 5-8
Copyright © McGraw-Hill Companies
Figure 5-8
Collagen Types (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 48
Collagen Types (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 49
2. Sheet-forming collagens:
Such as type IV collagen.
They have subunits produced by epithelial cells.
They are the major structural proteins of external
laminae and the basal lamina in all epithelia.
Collagen Types (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 50
3. Linking/anchoring collagens:
They are short collagens that link fibrillar collagens to
one another (forming larger fibers) and to other
components of the ECM.
Type VII collagen binds type IV collagen and anchors
the basal lamina to the underlying reticular lamina in
basement membranes.
Collagen Types (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 51
Collagen Synthesis
Connective Tissue, Dr. Emad I Shaqoura, IUG 52
Collagen synthesis occurs in many cell types especially
fibroblasts.
The initial procollagen α chains are made in the RER.
Many different α chains have been identified, varying in
length and sequence.
In the ER three α chains are selected, aligned, and folded as a
triple helix, which is the defining feature of collagens.
The triple helix (procollagen) undergoes exocytosis and is
cleaved to a rod-like collagen molecule that is the basic
subunit from which the fibers or sheets are assembled.
Collagen Synthesis (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 53
These subunits may be homotrimeric, with all three chains
identical, or heterotrimeric, with two or all three chains
having different sequences.
Different combinations of procollagen α chains produce the
various types of collagen with different structures and
functional properties.
Copyright © McGraw-Hill Companies
Figure 5-10
Collagen Synthesis (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 55
Because there are so many steps in collagen biosynthesis,
there are many points at which the process can be
interrupted or changed by defective enzymes or by disease
processes.
Collagen Synthesis (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 56
Type I collagen fibrils have diameters ranging from 20 to 90 nm and can be several micrometers in length.
Adjacent rod-like collagen subunits of the fibrils are staggered by 67 nm, with small gaps (lacunar regions) between their ends.
This structure produces a characteristic feature of type I collagen visible by EM: transverse striations with a regular periodicity.
Type I collagen fibrils assemble further to form large, extremely strong collagen fibers that are bundled by linking collagens and proteoglycans.
Copyright © McGraw-Hill Companies
Figure 5-11
Collagen Synthesis (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 58
Collagen type II (present in cartilage) occurs as fibrils but
does not form fibers or bundles.
Sheet-forming collagen type IV subunits assemble as a
lattice-like network in epithelial basal laminae.
Collagen (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 59
In the light microscope, collagen fibers are acidophilic;
they stain:
pink with eosin.
blue with Mallory trichrome stain.
red with Sirius red.
Because of the long and tortuous course of collagen bundles,
their length and diameter are better studied in spread
preparations than in histologic sections e.g., mesentery.
Connective Tissue, Dr. Emad I Shaqoura, IUG 60
Collagen fibers, H & E stain
Collagen fibers, Sirius red stain
Collagen fibers, Mallory trichrome stain
Collagen (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 61
Collagen turnover and renewal in normal connective tissue is generally a very slow but ongoing process.
In some organs, such as tendons and ligaments, the collagen is very stable, whereas in others, as in the periodontal ligament surrounding teeth, the collagen turnover rate is high.
To be renewed, the collagen must fist be degraded.
Degradation is initiated by specific enzymes called collagenases.
Collagenases clip collagen fibrils or sheets in such a way that they are then susceptible to further degradation by nonspecific proteases.
Various MMPs are secreted by macrophages and play an important role in remodeling the ECM during tissue repair.
Medical Application
Connective Tissue, Dr. Emad I Shaqoura, IUG 62
A keloid is a local swelling caused by abnormally large amounts of collagen that form in scars of the skin.
Keloids occur most often in individuals of African descent and can be a troublesome clinical problem to manage.
Not only can they be disfiguring, but excision is almost always followed by recurrence.
Reticular Fibers
Connective Tissue, Dr. Emad I Shaqoura, IUG 63
Consist mainly of collagen type III that forms an extensive
network (reticulum) of extremely thin heavily glycosylated
fibers (10% of the fiber content).
Staining properties:
Reticular fibers are seldom visible in H&E preparations.
They are characteristically stained black by impregnation with
silver salts (argyrophilic).
Reticular fibers are also periodic acid-Schif (PAS) positive.
Copyright © McGraw-Hill Companies
Figure 5-12
Reticular Fibers (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 65
Reticular fibers are present in the following sites:
1. The reticular lamina of basement membrane.
2. Surrounding adipocytes, smooth muscle and nerve fibers, and
small blood vessels.
3. The supportive stroma for the parenchymal secretory cells of
the liver and endocrine glands.
4. The stroma of hemopoietic tissue (bone marrow) and some
lymphoid organs (e.g., spleen and lymph nodes).
Elastic Fibers
Connective Tissue, Dr. Emad I Shaqoura, IUG 66
They are thinner than the type I collagen fibers.
They form sparse networks interspersed with collagen
bundles in many organs, particularly those subject to much
bending or stretching.
They form fenestrated sheets called elastic lamellae in the
wall of large blood vessels, especially arteries.
Staining properties:
They are not strongly acidophilic and stain poorly with H&E.
They are stained more darkly than collagen in other
stains such as orcein and aldehyde fuchsin.
Copyright © McGraw-Hill Companies
Figure 5-13
Elastic Fibers (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 68
Elastic fibers (and lamellae) are a composite of firillin
microfibrils embedded in a larger mass of cross-linked
elastin.
Both components are secreted from fibroblasts (and
smooth muscle cells in vascular walls) and produce elastic
fibers in a stepwise manner.
The properties of elastic fibers and lamellae result from
the structure of the elastin subunits and the unique
cross-links holding them together.
Copyright © McGraw-Hill Companies
Figure 5-14
Medical Application
Connective Tissue, Dr. Emad I Shaqoura, IUG 70
Fibrillins comprise a family of proteins involved in making the scaffolding necessary for the deposition of elastin.
Mutations in the fibrillin genes result in Marfan syndrome, a disease characterized by a lack of resistance in tissues rich in elastic fibers.
Because the walls of large arteries are rich in elastic components and because the blood pressure is high in the aorta, patients with this disease often experience aortic swellings called aneurysms, which are life-threatening conditions.
Ground Substance
Connective Tissue, Dr. Emad I Shaqoura, IUG 71
The ground substance of the ECM is a highly hydrated, transparent, complex mixture of macromolecules, principally of three classes:
1. Glycosaminoglycans (GAGs),
2. proteoglycans,
3. and multiadhesive glycoproteins.
It fills the space between cells and fibers in connective tissue.
Because it is viscous, acts as both a lubricant and a barrier to the penetration of invaders.
Copyright © McGraw-Hill Companies
Figure 5-16
Glycosaminoglycans
Connective Tissue, Dr. Emad I Shaqoura, IUG 73
Also called mucopolysaccharides.
They are long polysaccharides consisting of repeating
disaccharide units, usually a uronic acid and a hexosamine.
The hexosamine can be glucosamine or galactosamine, and
the uronic acid can be glucuronic or iduronic acid.
The largest, almost unique, and most ubiquitous GAG is
hyaluronic acid (HA or hyaluronan).
Glycosaminoglycans (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 74
Hyaluronic acid is a long polymer of the disaccharide
glucosamine-glucuronate.
It is synthesized directly into the ECM by an enzyme
complex, hyaluronate synthase, located in the cell membrane
of many cells.
Hyaluronic acid forms a dense, viscous network of polymers,
which binds a considerable amount of water, giving it an
important role in allowing diffusion of molecules in
connective tissue and in lubricating various organs and joints.
Glycosaminoglycans (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 75
All other GAGs are much smaller, sulfated, covalently attached
to proteins (as parts of proteoglycans), and are synthesized in
Golgi complexes.
The four major GAGs found in proteoglycans are: dermatan
sulfate, chondroitin sulfates, keratan sulfate, and heparan sulfate.
All of which have different disaccharide units and tissue
distributions.
Like hyaluronic acid, these GAGs are intensely hydrophilic,
contributing to the viscosity of ground substance, and are
polyanions, binding a great number of cations (usually sodium) by
electrostatic (ionic) bonds.
Connective Tissue, Dr. Emad I Shaqoura, IUG 76
Proteoglycans
Connective Tissue, Dr. Emad I Shaqoura, IUG 77
They are composed of a core protein to which are covalently
attached various sulfated GAGs.
They are synthesized on RER, mature in the Golgi, where the
GAG side chains are added, and secreted from cells by exocytosis.
Some proteoglycans, such as the major cartilage constituent
aggrecan, contain a greater mass of polysaccharide chains than
polypeptide.
In cartilage, aggrecan-hyaluronate complexes fill the space
between collagen fibers and cells and contribute greatly to the
physical properties of this tissue.
Copyright © McGraw-Hill Companies
Figure 5-17
Proteoglycans (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 79
Both matrix-linked and cell surface proteoglycans also bind
and sequester certain signaling proteins, for example
fibroblast growth factor (FGF).
Degradation of proteoglycans during the early phase of tissue
repair releases these stored growth factors that then stimulate
new cell growth and ECM synthesis.
Medical Application
Connective Tissue, Dr. Emad I Shaqoura, IUG 80
Because of their high viscosity, HA and proteoglycans
tend to form a barrier against bacterial penetration of
tissues.
Bacteria that produce hyaluronidase, an enzyme that
hydrolyzes hyaluronic acid and disassembles proteoglycans
complexes, reduce the viscosity of the connective
tissue ground substance and have greater invasive power.
Multiadhesive Glycoproteins
Connective Tissue, Dr. Emad I Shaqoura, IUG 81
They are very large molecules with branched oligosaccharide
chains.
All have multiple binding sites for cell surface receptors
(integrins) and for other matrix macromolecules.
They have important roles in the adhesion of cells to their
substrate.
Laminin provides adhesion for epithelial and other cells, with
binding sites for integrins, type IV collagen, and specific
proteoglycans.
All basal and external laminae are rich in laminin, which is
essential for the assembly and maintenance of these structures.
Copyright © McGraw-Hill Companies
Figure 5-18
Multiadhesive Glycoproteins (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 83
Fibronectin: synthesized largely by fibroblasts, has binding
sites for collagens and certain GAGs, and forms insoluble
fibrillar networks throughout connective tissue.
The fibronectin substrate provides specific binding sites for
integrins and is important both for cell adhesion and cellular
migration through the ECM.
Copyright © McGraw-Hill Companies
Figure 5-18
Multiadhesive Glycoproteins (cont’d)
Connective Tissue, Dr. Emad I Shaqoura, IUG 85
The integrin family of integral membrane proteins act as matrix receptors for laminin, fironectin, some collagens, and certain other ECM proteins.
Integrins bind their ligands in the ECM with relatively low affinity, allowing cells to explore their environment without losing attachment to it or becoming glued to it.
Integrins are heterodimers of two transmembrane polypeptides: the α and β chains.
Great diversity in the α and β chains allows the cells to have different specific ligands preferentially.
Cytoplasmic portions of integrins associate with peripheral membrane proteins that bind actin filaments.
Copyright © McGraw-Hill Companies
Figure 5-19
Interstitial Fluid
Connective Tissue, Dr. Emad I Shaqoura, IUG 87
A small quantity of free interstitial fluid, with ion
composition similar to that of blood plasma, is also present in
the C.T matrix.
Interstitial fluid contains plasma proteins of low molecular
weight that pass through the thin walls of capillaries.
Although only a small proportion of connective tissue
proteins are plasma proteins, it is estimated that as much as
one-third of the body’s plasma proteins are stored in the
matrix of connective tissue because of its volume and wide
distribution.
Medical Application
Connective Tissue, Dr. Emad I Shaqoura, IUG 88
Edema is the excessive accumulation of water in the
extracellular spaces of connective tissue.
This water comes from the blood, passing through the
capillary walls that become more permeable during
inflammation and normally producing slight swelling.
Copyright © McGraw-Hill Companies
Figure 5-20
Types of Connective Tissue
Connective Tissue, Dr. Emad I Shaqoura, IUG 90
Connective Tissue Proper
Embryonic Connective Tissue
Specialized Connective Tissue
Connective Tissue, Dr. Emad I Shaqoura, IUG 91
Connective Tissue Proper
Connective Tissue, Dr. Emad I Shaqoura, IUG 92
C.T Proper
Dense C.T
Regular Irregular
Loose C.T
Loose Connective Tissue
Connective Tissue, Dr. Emad I Shaqoura, IUG 93
Also called areolar tissue.
Is very common and generally supports epithelial tissue.
It comprises the lamina propria of the digestive system and fills the spaces between muscle and nerve fibers.
Usually well-vascularized whatever their location, thin layers of loose connective tissue surround most small blood vessels of the body.
The loose connective tissue typically contains cells, fibers, and ground substance in roughly equal parts, with predominance of fibroblasts and collagen fibers.
It has a delicate consistency; it is flexible and not very resistant to stress.
Copyright © McGraw-Hill Companies
Figure 5-21
Dense Connective Tissue
Connective Tissue, Dr. Emad I Shaqoura, IUG 95
It has the same components found in loose connective tissue,
but with fewer cells and a clear predominance of collagen
fibers over ground substance.
It is less flexible and far more resistant to stress than loose
connective tissue.
It has two types; irregular and regular.
Dense Irregular Connective
Connective Tissue, Dr. Emad I Shaqoura, IUG 96
In dense irregular connective tissue, bundles of collagen
fibers appear randomly interwoven, with no definite
orientation.
The collagen fibers form a tough three-dimensional network,
providing resistance to stress from all directions.
Dense irregular connective tissue is often found closely
associated with loose connective tissue, with the two types
frequently grading into each other and making distinctions
between them somewhat arbitrary.
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Figure 5-21
Dense Regular Connective Tissue
Connective Tissue, Dr. Emad I Shaqoura, IUG 98
The type I collagen bundles of dense regular connective
tissue are arranged according to a definite pattern, with
fibers and fibroblasts aligned in parallel for resistance to
prolonged or repeated stresses exerted in the same direction.
Common examples of dense regular connective tissue, are
tendons and ligaments.
Consisting almost entirely of densely packed collagen fibers,
they are white in the fresh state and almost inextensible.
The parallel, closely packed bundles of collagen are separated
by very little ground substance.
Dense Regular Connective Tissue
Connective Tissue, Dr. Emad I Shaqoura, IUG 99
The fibrocytes have elongated nuclei lying parallel to the fibers and sparse cytoplasmic folds that envelop portions of the collagen bundles.
The cytoplasm of these “tendinocytes” is rarely revealed in H&E stains.
Tendons are poorly vascularized and repair of damaged tendons is very slow.
In some tendons, the dense irregular connective tissue sheath is covered by flattened synovial cells of mesenchymal origin, which produce lubricant fluid (similar to the fluid of synovial joints) containing water, proteins, hyaluronate, and other GAGs.
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Figure 5-22
Medical Application
Connective Tissue, Dr. Emad I Shaqoura, IUG 101
Overuse of tendon-muscle units can result in tendonitis, characterized by inflammation of the tendons and their attachments to muscle.
Common locations are the elbow, the Achilles tendon of the heel, and the shoulder rotator cuff.
The swelling and pain produced by the localized inflammation restricts the affected area’s normal range of motion and can be relieved by injections of anti-inflammatory agents such as cortisone.
Fibroblasts eventually repair damaged collagen bundles of the area.
Mucoid Tissue
Connective Tissue, Dr. Emad I Shaqoura, IUG 102
Mucoid (or mucous) connective tissue is another embryonic type of connective tissue, found mainly in the umbilical cord and fetal organs.
With abundant ground substance composed chiefly of hyaluronic acid, mucoid tissue is jellylike with sparse collagen fibers and scattered fibroblasts.
Mucoid tissue is the principal component of the umbilical cord, where it is referred to as Wharton’s jelly.
A similar form of connective tissue is also found in the pulp cavities of young teeth, which remain as a postnatal source of mesenchymal stem cells.
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Figure 5-24
Reticular Tissue
Connective Tissue, Dr. Emad I Shaqoura, IUG 104
In reticular tissue, fibers of type III collagen form a delicate
3D network that supports various types of cells.
The fibrous network of this specialized connective tissue
is produced by modified fibroblasts called reticular cells
that remain associated with and partially covering the fibers.
It provides a framework with specialized microenvironments
for cells in hemopoietic tissue and some lymphoid organs
(bone marrow, lymph nodes, and spleen).
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Figure 5-23
Connective Tissue, Dr. Emad I Shaqoura, IUG 106