Connective Tissue pdf - Histology

163

They responsible for 1- providing and maintaining form in the body .

2- Provide a matrix that connects and binds the cells and organs to give support to the body . Is

formed by cells , fibers and ground substance.

The major constituent of connective tisue is Extracellular matrix

A- different combination of protein fibers( collagen ,reticular ,and elastic ) .

B- ground substance . Is hydrophilic ,viscous complex of

1- ( glycosaminoglycans and proteoglycans)

2- glycoproteins ( lamanin and,fibronectin) , which are binding to receptor proteins (integrins)

on the surface on cells and to other matrix Components.

The origin of connective tissue

Mesoderm (embryonic tissue) Mesenchyme tissue Mesodermal cell migrate

from their origin site, surrounding and penetrating developing organs



Cells of connective tissue

Table 5–1. Functions of connective tissue cells.

Cell Type

Representative Product or Activity

Representative Fun.

Fibroblast,
chondroblast,
osteoblast,
odontoblast

Production of fibers and ground substance

Structural

Plasma cell

Production of antibodies

Immunologic (defense)

Lymphocyte
(several types)

Production of immunocompetent cells

Immunologic (defense)

Eosinophilic
leukocyte

Participation in allergic and vasoactive reactions,
modulation of mast cell activities and the
inflammatory process

Immunologic (defense)

Neutrophilic
leukocyte

Phagocytosis of foreign substances, bacteria

Defense

Macrophage

Secretion of cytokines and other molecules,
phagocytosis of foreign substances and bacteria,
antigen processing and presentation to other cells

Defense

Mast cell and
basophilic
leukocyte

Liberation of pharmacologically active molecules
(eg, histamine)

Defense (participate in
allergic reactions)

Adipocyte

Storage of neutral fats

Energy reservoir, heat
production

164

Fibroblasts

1- Synthesize collagen , elastin ,glycosaminoglycans ,proteoglycans & multiadhesive glycoproteins.

that influence cell growth and differentiation

Growth factors

Involved in production of

Two stages of activity

Fibrocyte

1- Active Fibrobast 2- Quiescent

165

Mediccal application

When tissues are destroyed by inflammation or traumatic injury the main cell type involved in

repair is Fibroblast.

Fibrocyte reverts to Fibroblasts state and its synthetic activities are reactivated during wound

both fibroblasts and smooth muscle observed

,a cell with features of

myofibroblast

healing .The

during wound healing .Its activity is responsible for wound closure ,this process call Wound

contractio

Macrophages & the mononuclear phagocyte system

---

Characteristic features of macrophages seen in this TEM of
one such cell are the prominent nucleus (N) and the
nucleolus (Nu) and the numerous secondary lysosomes (L).
The arrows indicate phagocytic vacuoles near the
protrusions and indentations of the cel surface. X10,000.

166

 They are characterized by an irregular surface , a morphological expression of their active
pinocytotic and phagocytic activities .They have a well–developed Golgi complex, many

Lysosomes ,and R.E.R.

 Bone marrow Monocyt circulate in blood cross the wall of venules and
capillaries to penetrate the connective tissue, where they mature and acquire

morphological features of Macrophage

application

Medical

Epithelioid cell

When they are stimulated increase in size & clusters form

multinuclear giant cells

Several Macrophages may fuse to form

3- Macrophages participate in cell- mediated resistance to infection by bacteria, viruses, protozoa,

fungi ,and metazoans( parasitic worm)

4- Macrophages are also secretory cells that produce enzymes eg,collagenase & cytokiwhich

they exhibit increased tumor cell –killingnes

5- They participate in the processes of partial digestion and presentation of antigen to other cells

The langerhans cell in the dermis .

ex.

They have an important role in removing cell debris and damaged extracellular

components formed during the physiological involution processes. Ex .during

pregnancy the uterus increases in size and after parturition ,some of its tissue are

destroyed by the action of macrophages

Table 5–2.

Distribution and main functions of the cells of the mononuclear phagocyte system.

Cell Type

Location

Main Function

Monocyte

Blood

Precursor of macrophages

Macrophage

Connective tissue, lymphoid
organs, lungs, bone marrow

Production of cytokines, chemotactic
factors, and several other molecules that
participate in inflammation (defense),
antigen processing and presentation

Kupffer cell

Liver

Same as macrophages

Microglia cell

Nerve tissue of the central
nervous system

Same as macrophages

Langerhans cell

Skin

Antigen processing and presentation

Dendritic cell

Lymph nodes

Antigen processing and presentation

Osteoclast

Bone (fusion of several
macrophages)

Digestion of bone

Multinuclear
giant cell

Connective tissue (fusion of
several macrophages)

Segregation and digestion of foreign bodies

167

Mast cells

 Are oval to round connective tissues cells ,cytoplasm is filled with basophilic granules that
give a heterogeneous in appearance with a prominent scroll-like substructure ,that contains

Histamine & Heparin . They are abundant in the dermis & in the digestive & respiratory tracts.
 They originate from progenitor cells in bone marrow, circulate in the blood , cross the wall of
venules& capillaries & penetrate the tissue , they proliferate & differentiate.

the storage of chemical mediators of the inflammatory

cells is

The principal function of mast



response .

 The surface of mast cells contains specific receptors for immunoglobulin E (igE)
,which produced by plasma cells.

168

There are two populations of mast cells

1- Connective tissue mast cell

Is found in the skin & peritoneal cavity ; their granules contain the anticoagulant heparin.

2- Mucosal mast cell

Is present in intestinal mucosa and in the lungs ; their granules contain chondroitin sulfate .

Medical application

Release of the chemical mediators stored in mast cells promotes the allergic reaction known as

Mediate hypersensitivity reactions.

immunoglobulin E (IgE), a type of

The surface of mast cells contains specific receptors for

.Most IgE molecules are bound to the surface of

immunoglobulin produced by plasma cells

mast cells and blood basophiles ;very few remain in the plasma.

Plasma cells

Are large cells ,have a basophilic cytoplasm due to their richness in R.E.R.The nucleus is spherical

and eccentrically placed ,containing compact ,coarse heterochromatin alternating with lighter areas

of approximately equal size .this configuration resembles the face of a clock .

169

Medical application

is a glycoprotein that interacts specifically with

of antibodies

responsible for the synthesis

They are

an antigenic determinant.

uch as proteins,

A molecule that is recognized by cells of the immune system s

antigens

polysaccharides, and nucleoproteins) or molecules belonging to whole cells (bacteria,

infected cells).

tumor cells, or virus

protozoa,

The cells of the immune system do not recognize and react to the whole antigen molecule but

as antigenic determinants or

en known

instead react to small molecular domains of the antig

epitopes

171

Adipose Cells

Adipose cells (adipocytes; L. adeps, fat, + Gr. kytos) are connective tissue cells that have become

specialized for storage of neutral fats or for the production of heat. Often called fat cells, they are

discussed in detail in Chapter 6: Adipose Tissue.

Leukocytes

The normal connective tissue contains leukocytes that migrate from the blood vessels by diapedesis.

Leukocytes (Gr. leukos, white, + kytos), or white blood corpuscles, are the wandering cells of the

connective tissue. They migrate through the walls of capillaries and postcapillary venules from the

blood to connective tissues by a process called diapedesis. This process increases greatly during

inflammation (Figure 5–16). Inflammation is a vascular and cellular defensive reaction against

foreign substances, in most cases pathogenic bacteria or irritating chemical substances. The classic

signs of inflammation were first described by Celsus (first century A.D.) as redness and swelling

with heat and pain (rubor et tumor cum calore et dolore). Much later, disturbed function (functio

laesa) was added as the fifth cardinal sign.

Inflammation begins with the local release of chemical mediators of inflammation, substances of

various origin (mainly from cells and blood plasma proteins) that induce some of the events

characteristic of inflammation, eg, increase of blood flow and vascular permeability, chemotaxis,

and phagocytosis.

Chemotaxis

Is the phenomena by which specific cell types are attracted by some molecules ,is responsible for

the migration of large quantities of specific cell types to regions of inflammation .as leukocytes

,cross the venules and capillaries by Diapedesis ,invading the inflamed area.

171



Fibers of connective tissue

Collagen

Based on their structure and function ,they can be classified into the following groups:

: They form structures such as bones ,dentin ,tendons ,organ

Collagens that form fibers

capsules and dermis .

: Short structures that bind collagen fibrils to one another and

assciated collagen

Fibrile

other components of extracellular matrix

: Assemble in a meshwork that constitutes the structural

networks

Collagen that form

component of the basal lamina.

: Is present in anchoring fibrils that bind collagen

Collagen that form anchoring fibrils

fibers to the basal lamina

Collagen synthesis

 Fibroblast ,Chondroblast , Osteoblast , and Odontoblast producing collagen protein. The

(280 nm in

Tropocollagen

protein unit that form collagen fibrils is elongated molecule called

polypeptide chain

Tropocollagen consist of three sub uni

length and 1.5 nm in width) .

intertwined in a triple helix

 Differences in chemical structure of these polypeptide chains are responsible for the

various type of collagen

The transverse striations of collagen fibrils are determined by overlapping arrangement of the

tropocollagen molecules

172

Medical application

A large number of pathological conditions are directly attributable to insufficient or abnormal

collagen synthesis

(fibrosis) .It

accumulation of collage

Result from an excessive

progressive systemic sclerosis:

occurs in skin ,digestive tract muscle and kidney ,causing hardening and functional impairment of

implicated organ

mounts of collagen that form in scars of the skin

Is a local swelling caused by abnormal a

Keloid:

,especially in individuals of black African descent

Others disorders are illustrated in table 5-4.,

173

Reticular fibers

 They consist of collagen type III, in association with other types of collagen, glycoprotein and

proteoglycans.

,because of their

argyrophilic

12% hexoses. These fibers are called

Reticular fibers contain 6



affinity for silver salts.

 They are formed by loosely packed , thin fibrils bound together by interfibrillar bridges.They are

oietic organs

smooth muscle ,endoneurium ,and Hematop

found in

174

system

he elastic fiber

Oxytalan fibers

1- They are not elastic ,do not have elastin protein

2- Found in the zonule fibers of the eye & dermis.

fibromodulin

ding

inclu

They consist of a bundl of micro fibrils composed of glycoproteins,

molecule fibrilin

Elaunin fibers

An irregular deposition of the protein Elastin, appear between the Oxytalan fibers ,forming Elaunin

.They are found around sweat glands & in dermis .

Elastic fibers

III

Elastin gradually accumulates until it occupies the center of the fiber bundles, which are further

surrounded by a thin sheath of micro fibrils .They are rich in protein elastin ,they stretch easily in

response to tension

175

Medical application

MARFAN

Mutation in the fibrillin gene which it is necessary for deposition of elastin result in

, a disease characterized by a lack of resistance in the tissues rich in elastic fibers .

SYNDROM

Because the large arteries are in components of elastic system and because the blood pressure is

high in the aorta patients with disease often experience aortic rupture.

176



Ground substance

 Is a highly hydrated ,colorless and transparent complex mixture of macromolecules. It fills the

space between cells & fibers of connective tissue

 Act as both a lubricate & a barrier to penetration of invaders ,because of its viscosity.

Is formed mainly of three classes of components;

The ground substance

1- glycosaminoglycan ( GAG) 2- proteoglycan 3- multiadhensive glycoproteins

( GAG)

Glycosaminoglycan



Are linear polysaccharides formed by repeating disaccharide unit usually composed of a

uronic acid & a hexosamine .This linear chains (exception of hyaluronic acid ) are bound

proteoglycan molecule .

covalently to protein core forming a

the abundance of hydroxyl ,carboxyl & sulfat

These molecule are hydrophilic because of



groups in the carbohydrate moiety.

Proteoglycans

Are composed of a core protein associated with the four main GAG s ; Dermatan sulfate ;

Chondroitin sulfate ;Keratan sulfate ;& Heparan sulfate. They are distinguished by their

molecular diversity and can be located in cytoplasmic granules such Heparin of mast cells, in

the cell surface, and the extracellular matrix

177

Proteoglycans functions

1- Structural components of the extracellular matrix .

2- Anchoring cells to the matrix .

3- Both extracellular & and surface proteoglycan also bind many protein growth factor .

4- Because of their viscosity , they are acted as barrier to the penetration of bacteria and others

microorganism . Bacteria that produce hyaluronidase ,an enzyme that hydrolyzed hyaluronic acid

and other glycosaminoglycan, have great invasive power because they reduce the viscosity of

connective tissue ground substance

178

Multiadhesive glycoproteins

Are compounds that contain a protein moiety to which carbohydrates are attached



1- The protein moiety usually predominates and do not contain the linear polysaccharides

2- The carbohydrate moiety is frequently a branched structure .

Glycoprotein has an important in the adhesion of cells to their substrate and interaction



between neighboring adult and embryonic cells.

Several glycoprotein have been isolated from connective tissues



It has

lasts and some epithelial cells

Is a glycoprotein synthesized by fibrob

Fibronectin :

binding sites for cells ,collagen ,and GAG.

the

Is a large glycoprotein that participates in the adhesion of epithelial cells

Laminins :

basal lamina a structure rich in laminins

Medical application

 Both Fibronectin & Laminin participate in embryonic development and the increased

ability of cancer cells to invade other tissues has been postulate

 In addition to ground substance ,there is a very small quantity of Tissue fluid –

 Which it is similar to blood plasma in it content ion and diffusible substances.

 In some pathological conditions ,the quantity of tissue fluid may increase ,causing

 Edema ,which characterized by enlarged spaces ,caused by the increased in liquid

,between the components of connective tissue .

Edema may result from

1- Venous or lymphatic obstruction .

2- Decrease in venous blood flow ( eg. congestive heart failure )

3- Obstruction of lymphatic vessels due to parasitic plugs or tumor cells and chronic starvation.

4- Protein deficiency in a lack of plasma protein and a decrease in colloid pressure.

5- Increased permeability of the blood capillary or post capillary venule endothelium

resulting from chemical or mechanical injury

179



Types of connective tissue

connecctive tissue proper

connective tissue

loose

1- Supports many structures that are normally under pressure and low friction .

2- It fills spaces between groups of mucle cells .

3- Supports epithelial tissue .

4- Forms a layer that sheathes the lymphatic and blood vessels .

5- It is found in Papillary layer of the dermis , in the hypodermis , in glands & mucous membranes

supporting to epithelial cells.

181

denes connective tissue

It adapted to offer resistance and protection ,it is the same components of loose c .t., .There are

fewer cell and a clear predominance of collagen fibers .Is less flexible and far more resistant to

stress than is loose c. t.

It is known as:

irregular :

Dense

  The collagen fibers are arranged in bundles without a definite orientation .
 The collagen fibers form a three dimensional network .
  Provide resistance to stress from all directions .It is found in DERMIS.

lar:

Dense regu

 The collagen fibers aligned with the linear orientation of fibroblasts .
 Provide resistance to stresses exerted in same direction

181

Tendons are the most common example of denese regular C. T.

1- A re elongated cylindrical strictures attach striated muscle to bone .

2- They are white and inextensible .

3- They have parallel ,closely packed bundles of collagen.

4- Their fibroblasts contain elongated nuclei parallel to fibers.

(secondary

The collagen bundles of the tendons ( primary bundles ) aggregate into larger bundl

,that are enveloped by loose connective tissue.

bundles)

Elastic tissue


Is composed of bundles of thick ,parallel elastic fibers ,between these fibers is occupied thin

collagen fibers and flattened fibroblasts .

 It is yellow color , great elasticity .

 It is present in the yellow liquments of the vertebral column.

182

Reticular tissue

1- It forms three dimensional networks that support cells .

2- Specialized loose connective tissue consisting of reticular fibers associated with specialized

fibroblasts called Reticular cells It forms three dimensional networks that support cells.

3- Provides the architectural framework for hematopoietic organs & lymphoid organs ( bone

marrow ,lymph nodules ,and nodes and spleen)



Reticular cells are dispersed along this framework and cover the reticular fibers and ground

substance within cytoplasmic processes.

Mucous tissue

1- It is found in umbilical cord Where it is referred to as Wharton's jelly & found in the pulp of

young teeth.

2- Has an abundance of ground substance composed of hyaluronic acid .

3- It is a jelly tissue containing very few fibers .

4-The cells are mainly fibroblasts