Dr.

Mustafa Saad
(2022)

1
 Connective tissue (CT) is a type of body tissue
characterized by an abundant extracellular
matrix within which are dispersed different
types of cells and fibers.

Fig.1: Image showing the

components of CT: Cells,
Fibers and Ground
substance
2
 Functions
1. Provide and maintain form of organs.
2. Support different tissues and organs.
3. Connect and bind different body regions.
4. Provide a medium for diffusion of nutrients and
waste products.

3
 The Cells Of The Connective
Tissue

• Cells of the CT are, usually, not regularly arranged.

• The cells of CT could:
− Originate and remain in the CT all their lives (fibroblasts).
− Originate outside the CT and then come to the CT and
remain in it for the rest of their long lives (mast cells).
− Originate outside the CT and then come to the CT and
remain in it for a short period (neutrophils).

4
 Fibroblasts )1

• Most common cell in connective tissue.

• Function: Synthesizes fibers and produces
components of extracellular matrix.
• Active Fribroblasts and inactive Fibrocytes.
• Rarely divide. Mitosis resumes when they’re
needed under influence of several growth factors.

.Fibro- = fiber. -blast = forming 5

Fibroblasts:
• Abundant irregularly
branched cytoplasm
• Large, pale-staining
nucleus with prominent
nucleolus
• Rich in RER (rough
endoplasmic reticulum)
• Golgi apparatus well
developed
Fig.2: Histological features of fibroblasts.

Features of all protein producing cells 6

 Fibrocytes:
• Smaller than fibroblasts.
• Less cytoplasmic processes.
• Nucleus smaller and darker.
• Less RER.

• Myofibroblasts: Fibroblast cells with contractile

ability. Important in wound contraction.

-cyte = cell. Myo- = related to muscles, from greek mys = mouse (because movement of muscles resembles mice). 7
Fig.3: Fibroblast and
fibrocytes (arrows).
8
 2) Macrophages and the Mononuclear phagocyte
system

o Monocytes form in the bone marrow.

o Travel with blood and enter the connective tissues
by passing through capillary walls.
o Activated monocytes will form several types of
phagocytic cells in tissues.
o Macrophages in different tissues are given
different names.

Macro- = large. Micro- = small. Phages = eaters. Mono- = one, single. 9

Macrophages

Surface indentations and protrusions Lysosomes

Eccentric oval/kidney
shaped nucleus

Many RER and a Pseudopodia

well developed Golgi

Fig.4: Macrophages
and the process of
phagocytosis.

Debris Phagosome
Residual
bodies
10
Functions of Macrophages:
1) Phagocytosis (Microorganisms, neoplastic cells,
dead cells, debris, and abnormal extracellular
elements).
2) Destruction of red blood cells (metabolism of iron
and hemoglobin).
3) Antigen presentation to lymphocytes.
4) Release of cytokines and collagenases.

11
 3) Mast Cells

 Large, oval or round

cells.
 Cytoplasm filled with
basophilic secretory
granules.
 Nucleus small,
spherical and centrally Fig.5: Mast cells. Note how the
cytoplasm is intensely basophilic.
located (may be
obscured by granules).
12
  Depending on what’s contained in their secretory
granules, they may change the blue color of basic
dyes into a different color – metachromasia.

 Function: Release of heparin, histamine, and

various inflammatory molecules. They’re
important in inflammatory and allergic reactions.

Meta- = beyond. Chroma = color. 13

 4) Plasma Cells
 Large, ovoid cells.
 Basophilic cytoplasm
because it’s rich in RER
(no secretory granules).
 Golgi and centrioles occupy a juxtanuclear position
and appear pale.
 Nucleus spherical and eccentric. Has dark peripheral
regions alternating with lighter regions (clock-face
appearance).
 Short life span (10-20 days).
14
Juxta- = near, close to.
 Derived from B-Lymphocytes.
 Function: production of Antibodies.
 Stimulated by several local factors.

Fig.6: Plasma cells.

The cytoplasm is
basophilic. Note
the juxtanuclear
pale area (arrows)
and the clock-face
appearance of the
nucleus.

15
 Fibers of the Extracellular
Matrix
− Formed from proteins that polymerize into elongated
structures.
− The 3 main types are:
1) Collagen fibers (from protein Collagen)
2) Reticular fibers (from protein Collagen)
3) Elastic fibers (from protein Elastin)

16
 1) Collagen Fibers
• Present in different tissues: skin, bones, cartilage, basal
lamina, ligaments, and tendons. They give them strength.
• Several types of collagen protein exists.
• Collagen turn-over is slow in some organs, like tendons
where the collagen is stable. In the periodontal
membrane (which holds the teeth in their sockets),
collagen has a high turn-over rate.
• Collagen fibers may be in the form of (1)thick bundles (as
in tendons and ligaments), (2)fibrils (as those that anchor
the basal lamina to underlying tissues), or (3)networks.

17
 Collagen Molecule (Triplehelix)

Fig.7: The step-wise

formation of collagen fibers 18
Fig.8: Collagen fibers as seen by TEM (a) and LM (b). Note the striation
seen under the EM. Also note the pink color of the collagen fiber in (b). The
arrows point to nuclei of fibroblast.

19
Collagen disease

Disease Pathology Notes

Affects all body. A
Osteogenesis Genetic defect in collagen severe condition. May
imperfecta synthesis result in spontaneous
bone fracture.
Vitamin C deficiency Periodontal membrane
Scurvy (this vitamin is important is mostly affected and
for collagen synthesis) the teeth fall off
Sclerosis Accumulation of collagen Affects all body
Keloid Accumulation of collagen In skin wounds
 2) Reticular Fibers
o Formed by a type of collagen protein that is heavily
glycosylated.
o Thinner than Collagen fibers.
o Stain black with silver impregnation (argyrophilia).
o Form a network of fibers that holds the parenchyma of several
organs: liver, spleen, lymph nodes, bone marrow.
o Allow organs to stretch:
arteries, uterus.

Fig.9: Reticular fibers in lymph node (silver

impregnation).
21
 3) Elastic Fibers
 Thinner than collagen fibers.
 Forms a network dispersed between collagen bundles in
organs subject to stretching and bending. Elastic fibers may
form fenestrated sheets in the walls of large blood vessels
called Elastic lamellae.
 They provide Elasticity
for the organ
 They’re synthesized by
fibroblasts and smooth
muscle cells.
Fig.10: Two stains were used to
differentiate between collagen fibers (which
are red/pink) and elastic fibers (which are 22
darker in color).
 Ground Substance
• Is a highly hydrated transparent and viscous mixture of
complex macromelocules that fills the spaces between the
cells and the fibers in the connective tissue

- The Macromolecules are:

1) Glycosaminoglycans (GAG)
2) Proteoglycans
3) Glycoprotein

• The largest GAG is hyaluronic acid. This is the only GAG

synthesized on the cell membrane. Others are part of
proteoglycans and are synthesized inside the cell.
23
• Glycoproteins can bind to various components of the ECM
and the cell membrane. They’re, therefore, called
multiadhesive. They help keep the tissues together.
Examples: Laminin (in basal lamina).
• Laminin of the basal lamina can bind to integrin protein of
the epithelial cells and the other components of the basal
lamina.
• Laminin, therefore, plays an
important role in adhering the
epithelium to the underlying
connective tissue.

Fig.11: Laminin in the basal lamina under the

epithelium (immunohistochemical study). 24
 Classification of Connective Tissue
Connective Tissue
Mainly in embryos

Adult Embryonic

Proper Supportive Fluid

Loose Dense Bone Cartilage Blood

Areolar Collagenous Elastic Hyaline Lymph

Adipose Irregular Elastic

Reticular Regular Fibrocartilage

25
 Proper connective tissue is the connective tissue
in which the main type of cell that forms the
ECM is the fibroblast.

 Loose connective tissue: the fibers are loosely

arranged forming a network.

 Dense connective tissue: the fibers are densely

packed.

26
 Areolar Connective Tissue:
 A very common type of connective tissue. It gives some support
to organs and tissues.

 Features:
 Contain all three types of fibers arranged loosely.
 All types of connective tissue cells (especially fibroblasts and
macrophages) are present here.
 All these components
are embedded in an
abundant semi-fluid
ground substance.
 It’s highly vascular.

Areolar = small spaces. 27

 Found:
1. Under epithelia.
2. Around glands.
3. In the spaces between muscle and nerve fibers.
4. Around blood and lymphatic vessels.
5. It fills many small spaces making it the ‘packing material’ of
our body.

 Functions:
1. It gives organs their shape.
2. It is a medium for the diffusion of gases, nutrients, and waste
product.
3. It is usually the first tissue where microorganisms and foreign
particles enter the body; therefore, it’s an important site for
immune and inflammatory responses.

28
Fig.12: Left: Skin. Right: Esophagus. In both images, the loose connective
tissue is indicated by L. Note its position under the epithelium. (The Ds in
both images indicate dense collagenous irregular connective tissue).

29
 Reticular Tissue:
 Composed mainly of loosely arranged
reticular fibers forming a network
within haematopoietic organs (bone
marrow, spleen) and lymph organs.
 Fibers formed by Reticular cells
(modified fibroblasts) whose
cytoplasmic processes extend on the
reticular network forming a cell-lined
sponge-like structure.
 Macrophages are also present in this Fig.13: Reticular tissue.
tissue. Note how there are several
spaces in this tissue giving
it a sponge-like appearance.
30
 Dense Collagenous Connective Tissue:

 A type of connective tissue that has numerous

densely packed collagen fibers with few cells and
ground substance. Highly resistant to stress.
 Could be irregular or regular
1. Irregular: fibers arranged in no specific orientation
forming a 3-dimensional network that resist stress
from all directions. It is found in organ subject to
great stresses (see Figure 12).

31
2) Regular: fibers arranged parallel to each other in a
specific orientation with flattened fibroblasts dispersed
between them. Provides great resistance to traction
forces. Found in tendons and some ligaments giving the
living tissue a white color.

Fig.14: Dense collagenous

regular connective tissue
of a tendon (longitudinal
section).
32
 Dense Elastic Tissue:

 Composed mainly of elastic fibers. Found in aorta, some

ligaments, and true vocal cords. Gives the organ elasticity.

33
Fig.15: Elastic tissue in the aorta.
34
 Is a type of connective tissue in which adipocytes
predominate.
 It’s present throughout the body.
 It constitute about 15-20% of the body weight of
males with normal weight, and 20-25% of females
body weight.
 It could White (WAT) or Brown (BAT).

35
 Functions of Adipose Tissue
1) Storage of energy in the form of Triglycerides.
2) Endocrine role by the release of certain hormones and
cytokines.
3) Insulator, because it’s a poor conductor of heat.
4) Fills the large spaces between tissues and keeps some
organs in place.
5) Subcutaneous fat helps shape the surface of the body.
6) Fat pads act as shock absorbers (palms and soles).
7) Warming of blood (brown fat).
36
 White Adipose Tissue
o Specialized in energy storage in white adipose cells.

o Depending on diet, its color varies from white to

bright-yellow.

o Features of white adipose tissue:

1) Fibroblasts and macrophages are present in the tissue.
2) Reticular fibers form a network that supports
individual adipose cells and bind them together.
3) Divided by connective tissue partitions into
incomplete lobules.
4) Highly vascularized. 37
 Histological features of White Adipocytes

1. Large spherical cells with a single large fat droplet

(unilocular).
2. Flattened nucleus on one side (pushed by the droplet).
3. A thin film of cytoplasm around the droplet with thicker
cytoplasm around the nucleus.
4. Around the nucleus are several mitochondria, Golgi
apparatus, polyribosomes, and poorly developed RER.
5. In the thin film of cytoplasm, there are well developed SER
(smooth endoplasmic reticulum) and pinocytotic vesicles.
6. The droplets are surrounded by Vimentin intermediate
filament.
7. The cell is surrounded by a thin basal lamina.
38
Fig.16: The image above shows the features
of white adipocyte. On the right, the image
shows the typical appearance of fatty tissue in
a routine preparation. Fat droplets dissolve
during tissue preparation and the cell appears
as a thin ring with the nucleus projecting on
one side (the signet-ring appearance).

39
Fig.17: Special stains were used to preserve the fat droplet.

40
Clinical aspects of White adipose tissue

1) WAT secretes the hormone Leptin which is a ‘Satiety

Factor’  Could obesity be treated by hormonal
therapy?
2) Adiponectin is released by adipocytes. The larger the
adipocyte, the less adiponectine it releases. This
hormone protects against diabetes and other diseases.
3) Obesity is characterized by a state of chronic mild
inflammation because WAT secretes several
inflammatory factors  Could these be related to the
cardiovascular or diabetic complications of obesity?

41
4) Although histologically
similar, Visceral and
Subcutaneous WAT
have different gene
expression. The
visceral WAT is more
dangerous to health 
Could obesity be
treated by gene
therapy?

42
5) At birth, fat stores are already formed and
distribution and density varies with age and gender.
 Obesity in adults is hypertrophic (results from
increase in size of the already present adipocytes). In
Children, the obesity could be hyperplastic (increase
in the number of cells) because new adipocytes can
be formed from precursor cells that are still present
at this age. Such obese children are more liable to
develop a more severe hypertrophic obesity because
they have more adipocytes.  Treat/prevent obesity
at an early age.
43
 Brown Adipose Tissue
• Specialized in heat production.
• Brown adipocytes are smaller than white adipocytes,
polygonal, with multiple fat droplets (multilocular).
They have numerous mitochondria and a central
spherical nucleus.
• Cells arranged in an almost epithelial arrangement
around a blood capillary. The tissue is divided into
lobules by connective tissue partitions.
• The brown color is due to the mitochondria and the
blood vessels. 44
Fig.18: Above, a brown
adipocyte, note the several small
fat droplets. Right, brown
adipose tissue, note how the cells
surround a blood vessel (BV).
45
• At birth, brown adipose tissue is maximal for body
weight. It then decreases with age.
• In adults, it’s found in scattered areas especially
around the kidneys, the adrenals, the aorta, and in
the mediastinum.
• It increases during cold adaptation.

46
 Bl
oo
d
47
• Blood Is a fluid type of connective
tissue characterized by having a
liquid extracellular matrix
(plasma) in which are dispersed
the formed elements of blood:
(1)
Red blood cells (Erythrocytes),
(2)
White blood cells (Leukocytes)
and (3)Platelets (Thrombocytes).

• Functions of blood:
1) Transportation: Gases, nutrients, waste products,
hormones.
2) Regulation: pH, body temperature.
3) Protection: Clotting, white blood cells, proteins
(antibodies). 48
Components of Blood
Blood
Plasma Formed Elements
of blood 55% of blood 45%
Water Red White
Solutes
of 91% Blood Blood Platelets
)mostly protein( Cells Cells
plasma

Proteins
Other
Mostly( Solutes
)Albumin

49
Formed Elements of Blood
Erythrocytes (Red Blood Cells)
 The most abundant type of cell in blood
 This cell is normally only present in
blood inside the blood vessels. 8µm

 Biconcave disc in shape. This

increases surface area.
 Lack nucleus and other organelles.
Cytoplasm is filled with the oxygen-
carrying protein hemoglobin. Because
it has no mitochondria, it doesn’t use
oxygen.
50
 Strong, flexible plasma membrane. This allows the
cell to change its shape without rupturing as it
passes through narrow capillaries.

The flow rate in this animation has

been tripled. An average cycle actually
takes about 60 seconds.

 Life span about 120 days.

51
Functions of the red blood cells
1) The hemoglobin in the RBCs functions in the
transportation of:
 Oxygen – this is the main function of RBCs

 CO
2
 Nitric Oxide (NO) – this gas is a vasodilator that
helps in increasing blood flow
2) Glycolipids in plasma membrane are responsible for
ABO and Rh blood groups.
3) When RBCs are destroyed by some microorganism,
they release substances that can kill the
microorganism.
• Is there a more direct role for RBCs in immune
response?
52
 Leukocytes (White Blood Cells)

 Wandering cells: formed in bone marrow, circulate in

blood and enter tissues.
 Respond to local factors in inflammation.

Fig.19: Leukocytes in inflamed

tissue. 53
Classification of Leukocytes
Neutrophils

Granulocytes Acidophils / Eosinophils

Has specific granules

Basophils
Leukocytes

Monocytes
Agranulocyte
T-Lymphocytes
s
Lymphocytes
No specific granules
B-Lymphocytes

54
Granulocytes Neutrophils Eosinophils Basophils

Abundance
(% of 60-70% 2-4% 0.5%
leukocytes)
Multilobed (with
S shaped
inactive X-chromosome
Nucleus Bilobed (obscured by
of females appearing as
granules)
a drumstick appendage)
Sparse and stain Large
Granules Large eosinophilic
variably basophilic
• Defense against Release of
Function Phagocytosis parasitic infection inflammatory
• Allergic reactions molecules

55
Agranulocytes:

Monocytes (5%):
 Kidney or U-shaped nucleus.
 Cytoplasm basophilic.
 Function: formation of macrophages.

Lymphocytes (28%):
 Variable in size.
 Nucleus very dark and occupies most of the cell.
 Functions:
 T-cells  Cell mediated immunity
 B-cells  Antibody-mediated immunity

56
 Platelets/ Thrombocytes
 Large cells in the bone marrow called Megakaryocytes send
processes into blood vessels. These processes will splinter
into small fragments called Platelets.
 This process continues until each megakaryocyte gives rise to
about 2000 platelets.
 Each platelet is a disc-shaped structure surrounded by cell
membrane and containing no nucleus but numerous vesicles
containing blood-clotting promoting factors.
 Short life span: 5-9 days.
 Function: Stops bleeding by the formation of (1) platelet plug
and (2) blood clot.
57
ABO Blood Groups
 Blood group is type of blood designated to a person based on
the presence/absence of an antigen on the surface of RBCs.
 The ABO blood groups are based on the A and B antigens.
 Reason for antibodies presence not clear.

Antibody in
Blood Type Antigen on RBCs
Plasma
A A Anti-B
B B Anti-A
AB A&B None
O None Anti-A & Anti-B
58
 Each blood group can give to
itself
 AB is the Universal Recipient
 O Is the Universal Donor
59
Thank
You
There are two ways of spreading light: to be
the candle or the mirror that reflects it.

‫كن عالما او متعلما و ال تكن ثالثهما فتخسر‬

60