Connective tissue (CT)

 The term connective tissue is traditionally applied to a basic

type of tissue provides structural and metabolic support
for other tissues and organs throughout the body.
• CT comprises a diverse group of cells within a tissue-
specific extracellular matrix
• Different types of CTs are responsible for a variety of
functions.
• CTs are named because of one of its ordinary function i.e.
connecting different types of tissues and organs, carrying
their blood & nerve supply. 1
 Functions of CTs
 The major functions of CTs include:
 They bind together, support, and strengthen other body
tissues;
 Protect and insulate internal organs;
 Compartmentalize structures such as skeletal muscles;
 Serve as the major transport system within the body (blood, a
fluid connective tissue);
 They are the primary locations of stored energy reserves
 They are the main source of immune responses.
2
General features of connective tissues,,,
• In contrast to epithelial tissues, CT do not usually occur
on body surfaces.

• Also, unlike epithelial tissues, CTs usually are highly

vascular; that is, they have a rich blood supply.

• Exceptions include cartilage, which is avascular, and

tendons, with a scanty blood supply.

• Except for cartilage, connective tissues, like epithelial

tissues, are supplied with nerves.
3
 Connective tissue extracellular matrix
• The extracellular material, has 3 major components:
protein fibers, ground substance and fluid.
• Three types of protein fibers help form most CT.
I. Collagen fibers, which resemble microscopic ropes, are
flexible but resist stretching.
II. Reticular fibers are very fine, short collagen fibers that
branch to form a supporting network.
III. Elastic fibers have a structure similar to that of coiled
metal bed springs; after being stretched, they can recoil to
their original shape.
4
 Connective tissue cells
• Embryonic cells called mesenchymal cells give rise to the cells
of CT. Each major type of CT contains an immature class of
cells

• These immature cells are called fibroblasts in loose & dense

CT, chondroblasts in cartilage,& osteoblasts in bone.

• Blast cells retain the capacity for cell division and secrete the
extracellular matrix that is characteristic of the tissue.

• The immature cells differentiate into mature cells with names

ending in -cyte, namely, chondrocytes and osteocytes.
5
 Connective tissue cells,,,
 The types of cells in CT vary according to the type of tissue

Fixed (Resident)cells: The cells that make up the resident

cell population are relatively stable; they typically exhibit little
movement & 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.
6
 Connective tissue cells,,,
Transient or Wandering 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.
Transient macrophages.
7
 Classification of CT
• Two major categories of connective tissue are

I. embryonic connective tissue and

II. adult connective tissue.

 Adult connective tissue consists of three types:

 connective tissue proper (loose and dense),

 supporting connective tissue (cartilage and bone), and

 fluid connective tissue (blood). 8

 Connective Tissue Proper
 Loose CT consists of relatively few protein fibers with
numerous spaces filled with ground substance and fluid.
• Three subdivisions of loose connective tissue are areolar,
adipose, and reticular.
 Areolar has extracellular matrix consisting mostly of collagen
fibers and a few elastic fibers.
 Adipose tissue consists of adipocytes,(fat cells), which contain
large amounts of lipid for energy storage.
 Reticular tissue forms the framework of lymphatic tissue, such
as in the spleen and lymph nodes, as well as in bone marrow
and the liver 9
 Connective Tissue Proper,,,
 Dense CT has a relatively large number of protein fibers that
form thick bundles & fill nearly all of the extracellular space.
These protein fibers are produced by fibroblasts.
 There are 2 major subcategories of dense CT: collagenous
and elastic.
 Dense collagenous CT has an extracellular matrix consisting
mostly of collagen fibers.
 Structures made up of dense collagenous CT include tendons,
ligaments, many capsules that surround organs, such as the
liver and kidneys.
• The elastic fibers allow the tissue to stretch and recoil.
Examples include the dense elastic CT in the vocal cords,
in elastic ligaments, and in the walls of large arteries.
10
 Supporting Connective Tissue
• Supporting CT consists of cartilage and bone

• Cartilage is composed of chondrocytes(cartilage cells).

• Collagen in the matrix gives cartilage flexibility and strength.

• Cartilage heals slowly after an injury because blood vessels do

not penetrate it.

• There are three types of cartilage:

– Hyaline cartilage

– Fibrocartilage

– Elastic cartilage 11
 Supporting Connective Tissue,,,
• Hyaline cartilage is the most abundant type of
cartilage.
• It covers the ends of bones where they come
together to form joints.
• Hyaline cartilage also forms the cartilage rings of
the respiratory tract, the nasal cartilages, and
the costal cartilages, which attach the ribs to the
sternum (breastbone). 12
 Supporting Connective Tissue,,,
• Fibrocartilage has more collagen than does hyaline cartilage, and
bundles of collagen fibers.

• Fibrocartilage is found in the disks b/n the vertebrae (bones of the

back) and in some joints, such as the knee and temporomandibular
(jaw) joints.

• Elastic cartilage contains elastic fibers in addition to collagen and

proteoglycans.

• Elastic cartilage is able to recoil to its original shape when bent. The
external ear, epiglottis, and auditory tube contain elastic
cartilage 13
Supporting Connective Tissue,,,

14
 Supporting Connective Tissue,,,
• Bone is a hard CT that consists of living cells and a
mineralized matrix.

• Osteocytes(bone cells), are located within lacunae.

• The strength and rigidity of the mineralized matrix

enables bones to support and protect other tissues.

• Based on organization of extracellular matrix & cells,

bone is classified as Compact bone and Spongy bone.

15
 Functions of Bone & other skeletal tissues
 Support. Bone is hard and rigid; cartilage is flexible yet strong.
Cartilages support nose, ear, thoracic cage and trachea.
Ligaments- bind bone to bone
 Protection. Skull around brain; ribs, sternum, vertebrae protect
organs of thoracic cavity
 Movement. Produced by muscles on bones, via tendons.
Ligaments allow some movement between bones but prevent
excessive movement
 Storage. Ca and P. Stored then released as needed. Fat is also
stored in yellow marrow cavities
 Blood cell production. Red bone marrow that gives rise to blood
cells and platelets

16
 Bone Histology
• Bone or osseous tissue
• Four types of cells are present in bone tissue:
• Osteogenic/osteprogenitor cells: unspecialized stem cells
• Osteoblasts:- Bone building cells
• Osteocytes: Mature bone cells
• Osteoclasts: bone resorbing cells
Bone matrix.
Organic: collagen and proteoglycans
Inorganic: hydroxyapetite, CaPO4 crystals
17
18
 Osteoprogenitor cells
Osteoprogenitor cells are derived from embryonic
mesenchymal cells

They retain their ability to undergo mitosis

throughout postnatal life and have the potential to
differentiate into osteoblasts .

Osteoprogenitor cells are most active during the

period of intense bone growth.

19
 Osteoblast cells
Osteoblasts are derived from osteoprogenitor cells and
develop under the influence of the bone morphogenic
protein (BMP) family & transforming growth factor-β.

 The newly secreted organic matrix is called osteoid.

 Collagen forms strands of spiral fibers around which the

inorganic matrix is deposited

 Influence deposit of Ca++, PO4.

20
 Osteoblast cell,,,

Osteoblasts (Ob)
Osteoclasts (Oc) 21
 Osteocytes
 are mature bone cells, derived from osteoblasts, that are
housed in lacunae within the calcified bony matrix.
 Osteocytes conform to the shape of their lacunae.
 Their nucleus is flattened, & their cytoplasm is poor in
organelles,
 Although osteocytes appear to be inactive cells, they secrete
substances necessary for bone maintenance.
 They are responsible for maintaining the bone tissue.
 Osteocytes stimulated by calcitonin; inhibited by
Parathyroid hormone. 22
Osteocytes,,,

23
 Fluid Connective Tissue
• Blood is a fluid CT in which cells, i.e. Blood
cells are suspended in a liquid matrix called
Plasma.
• A human adult has about 5 liters of blood,
which is roughly 7-8% of the total body weight
• A typical sample of blood is 45% formed
elements (blood cells) & 55% plasma by
volume.
• The formed elements include erythrocytes (red
blood cells), leukocytes (white blood cells)
and platelets
24
 Functions of blood
 Functions principally for the transport of gases (oxygen &
carbon dioxide), nutrients, metabolic waste products,
cells, & hormones.
 Carries waste products such as carbon dioxide.
 Transports hormones to target tissues.
 Carries drugs, elements and cells that protects the body from
infections and foreign bodies.
 A homeostatic role based on its thermoregulatory and
buffering capacity (acid-base balance).
25
Composition of whole blood.

26
 Plasma
• Blood consists of cells and a protein rich fluid called plasm,
• More than 90% of plasma by weight is water, which serves as
the solvent for a variety of solutes, including proteins, dissolved
gases, electrolytes, nutrients, regulatory substances, and waste
materials.
• The solutes in the plasma help maintain homeostasis, a steady
state that provides optimal pH and osmolarity for cellular
metabolism.
• It is an intercellular aqueous solution (pH 7.4) that imparts blood
its fluid properties. 27
 Plasma,,, It contains:
 Water
 Carbon dioxide
 A straw-  Glucose
coloured
liquid that  Amino acids
carries the  Proteins
cells and
the  Minerals
platelets  Vitamins
which help
blood clot.  Hormones
 Waste materials
like urea, uric acid.
28
 The functions of plasma
 Maintaining optimal blood pressure and volume
 Supplying critical proteins for blood clotting and immunity.
 a medium for exchange of vital minerals such as Na+, K+, Ca++,
& phosphorus to maintain proper ionic balance.
 Nutrients, such as glucose, proteins, lipids, and hormones are
carried from site of absorption to various areas of the body by
blood plasma.
 Moreover, plasma transports nitrogenous wastes (such as
urea, uric acid & creatinine), excess salt & water to be removed
from the blood by the kidneys.
29
 Blood cells
 Erythrocytes (RBC)

 Leukocytes (WBC)

 Platelets
30
Erythrocytes(RBCs)
 are terminally differentiated
cells
 Erythrocytes are anucleate,
biconcave discs.
 They lack nucleus & other
cytoplasmic organelles but
packed with the O2-carrying
protein hemoglobin.
 Under normal conditions,
these corpuscles never leave
the circulatory system.
31
 Erythrocytes (RBCs),,,
 They are approximately 7.5µm in diameter, 2.6µm thick at
the rim & 0.75µm thick at the center ,
 The average volume is 90 to 95 cubic
micrometers.
 This biconcave shape provides a
large surface-to-volume ratio and
facilitates gas exchange.
 The normal concentration of RBC is
approximately 3.9–5.5 million per
microliter in women and 4.1–6
million per microliter in men.
32
 Hemoglobin
• RBC contain hemoglobin(68 kilodaltons), a protein
specialized for the transport of oxygen and carbon dioxide.

• Erythrocytes transport O2, Co2 bound to hemoglobin.

• A monomer of hemoglobin is similar in composition and

structure to myoglobin, the oxygen-binding protein found in
striated muscle.

• The disc shape of the erythrocyte facilitates gas exchange

because more hemoglobin molecules are closer to the plasma
membrane than they would be in a spherical cell.
33
 Human Blood Groups
 at least 30 commonly occurring antigens and hundreds
of other rare antigens, each of which can at times cause
antigen-antibody reactions, have been found in human
blood cells, especially on the surfaces of the cell
membranes.
 but most of the antigens are weak
 two particular types of antigens are much more likely
than the others to cause blood transfusion reactions (the
O-A-B system antigens and the Rh system antigen).
34
 Human Blood Groups,,,
 Blood grouping depends on the presence of antigens
(agglutinogens) on the surface of RBC membrane

• RBCs contain protein/glycoproteins/lipoproteins on their surface

with antigenic effect  these antigens are:

 unique to the individual

 recognized as foreign (antigenic) if transfused into another

individual who does not have those same antigens on RBC
membrane

 presence or absence of these antigens is used to classify blood

groups.
35
 ABO Blood Group
• Based on the pesence or absence of two antigens
(agglutinogen) (agglutinogen A and agglutinogen B)
• according to ABO blood grouping system blood types of
individuals are classified into four types of blood
1. When agglutinogen A is present on RBCs, the blood is
type-A
2. When agglutinogen B is present on RBCs, the blood is
type-B
3. When both agglutinogens A & B exist together : type-AB
4. When neither agglutinogen A nor B are present: type-O
36
 Agglutinins (antibodies)
• In the ABO blood grouping, plasma contains agglutinins
(antibodies) against the missing antigen:
 Anti-A antibodies
 Anti-B antibodies
 Existence of agglutinogen and agglutinins:
 when agglutinogen A is present on RBCs, anti-B anitbody in
plasma.
 when agglutinogen B is present on RBCs, anti-A anitibody in
plasma.
 when agglutinogen A & B exist together, neither anti-A nor anti-B
antibodies present in the serum.
 when no both agglutinogens (A and B) on RBCs, both anti-A and
anti-B antibodies are present in the serum (O blood type).
37
Antigen & antibody coexistence in the ABO
Blood groups
Antigen/Agglutinogen
Blood type Antibody in Blood Plasma
On RBCs

A A anti-B

B B anti-A

AB A&B Neither

O Neither both anti-A & anti-B

38
Antigen & antibody coexistence in the ABO
Blood groups,,,

39
 Leukocytes (white blood cells or WBCs)
• They are colorless because they contain no
hemoglobin, however, each cell has a nucleus.
• In the bloodstream, they are spherical in shape
and mobile.
• According to the type of cytoplasmic granules
and the shape of nuclei, leukocytes are classified
into:-
A-Granular leukocytes:- (which contain specific
granules and lobulated nuclei):
1-Neutrophils 55-70%
2-Eosinophils 2-4%
3-Basophils 0- 0.5% 40
 Leukocytes,,,
B-Agranular leukocytes:- (which do not contain specific
granules with non-lobulated nuclei):
1-Lymphocytes 20-40%
2-Monocytes 3-8%
 Total leukocytic count:-It is the total number of leukocytes
per cubic millimeter.
 In normal adult the ‘total leukocytic count’ is between
5,000-10,000 per cubic mm.
 Differential leukocytic count:-It is the percentage of each
type of leukocytes to the total number of leukocytes.
41
Leukocytes

Granulocytes

Agranulocytes

42
 Leukocytes,,,
 Functions of leukocytes:-
1-The role of leukocytes in general is essentially a protective
one.
 They protect the body in a number of ways against the
infectious organisms.
2-Moreover, leukocytes perform their main functions outside
the blood stream after they have entered loose C.T.
 There is a great correlation between leukocytes and some
cells of loose C.T. (histiocytes or macrophages, mast cells
and plasma cells). 43
 Leukocytes,,,
• All leukocytes are key players in the defense against
invading microorganisms, and in the repair of injured
tissues, specifically leaving the microvasculature in
injured or infected tissues.

• In a process called diapedesis (Gr. dia, through + pedesis,

to leap), the leukocytes send extensions through the
openings between the endothelial cells, migrate out of
the venules into the surrounding tissue space, and head
directly for the site of injury or invasion.
44
 Neutrophils
 are the most numerous leukocytes in peripheral blood
and account for about 50-70% of the circulating
leukocytes.

 They are also called polymorphonuclear neutrophils or

polymorphs
• Leave circulation in large numbers in response to bacterial
infection and tissue injury in acute inflammations.
• Their nucleus is lobulated in appearance, of 2-4 lobes
connected to each other by thin threads of chromatin.
45
Neutrophils

46
Red blood cells and Neutrophil in the center

47
 Functions of neutrophils
 Neutrophils are the first line of defense against
invading organisms especially bacteria.
 Neutrophils (in blood stream) are attracted to bacteria
(in C.T.) by chemical substance liberated by the
organism a process known as ‘‘Chemotaxis’’.
 Once neutrophils are outside the vessel in the C.T
they move toward bacteria, which they rapidly
phagocytose and destroy it.
48
 Eosinophils
Large size cells (10-14 m in diameter)

 a characteristic bilobed nucleus

 Constitute about 2-4% of total leukocytes

 Refractile crystalloid eosinophilic granules

49
Eosinophils,,,

50
function of eosinophil
- Anti-allergic - (phagocytosis of Ag-Ab complex)
- anti-parasitic against helminthic worms and protozoa
 It occurs in allergy and parasitic infection.
 Eosinophils also phagocytose antigen-antibody complexes and
modulate inflammatory responses in many ways.
 They are an important source of the factors mediating allergic
reactions and asthma

51
 Basophils
 Large size cells (10-12 m in diameter)

 S shaped nucleus (bilobed)

 are the least numerous of the white cells accounting for less than
1%.

52
Basophils,,,

53
Function of basophils
 Mediate inflammatory response.
 They bind to immunoglobulin E (IgE)
in allergic reaction and leads to release of its vasoactive substance
(Histamine and heparan sulfate).
 Play a role in hypersensitivity (anaphylactic shock) (i.e.
vasodilatation and smooth muscle contraction).
 are thought to supplement the function of mast cells in immediate
hypersensitivity rxns
 Basophilia means:
 Increase in number of basophils (more than 1%)
 Occurs in allergy and liver cirrhosis.
54
 Lymphocytes
 are the primary functional cells of the immune system.
 actively involved in autoimmune diseases, inflammatory
responses, allergic reaction, tumor control and
transplantation rejection/graft rejection.
 They are round and have condensed nucleus.
 Produces antibodies & other chemicals responsible for
destroying microorganisms.
 Smallest in size but are the 2nd most numerous (20-30% of
leukocytes in circulation),increased number are commonly
seen during viral infections. 55
 Lymphocytes,,,
 are the most common agranular leukocyte & are unique
in their ability to return from tissues back to the blood
stream.

56
 Lymphocyte,,,
• Morphologically lymphocytes are similar but can be
subdivided into functional groups by distinctive surface
molecules (called “cluster of differentiation” or CD markers)
that can be distinguished using antibodies with
immunocytochemistry.

 Three functionally distinct types of lymphocytes are present in

the body: T lymphocytes, B lymphocytes, & natural killer (NK)
cells.

• They have diverse roles in immune defenses against invading

microorganisms & certain parasites or abnormal cells. 57
 Lymphocyte
 T lymphocytes (T cells) are so named because they undergo
differentiation in the thymus.

 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.
58
 Comparison of B and T lymphocytes
B-Lymphocytes T-Lymphocytes
 Percentage 15% of the circulating 80% of the circulating
lymphocytes lymphocytes

 Development
In the bone marrow from In the bone marrow from
(CFU-Ly B) (CFU-Ly T)

 Maturation & In the cortex and medulla of the

Immanocompetency In the bone marrow
thymus
 Plasma membrane Have Fc receptors and
Have T-cell receptors
antibodies
 Site in Peripheral
Lymphoid Organs Widely distributed in lymph In thymus dependent zone of
node, spleen, lymph node & spleen

 Life Span 3 months May live for years

 Function Humeral immunity Cell mediated immunity
59
 Monocytes
 Monocytes are the precursors of the cells of the
mononuclear phagocytotic system.

 Monocytes, the largest of the circulating blood cells

(average diameter, 18 m)., enter the CT spaces, where
they are known as macrophages.

 Nucleus is large eccentric, indented & kidney shaped

 Cytoplasm is bluish-grey and has small number of

azurophilic granules, with occasional vacuole like space

60
 Monocytes,,,
 Monocytes remain in the blood for only about 3 days.
 They travel from the bone marrow to the body
tissues, where they differentiate into the various
phagocytes of the mononuclear phagocytotic
system— that is, CT macrophages, osteoclasts,
alveolar macrophages, perisinusoidal macrophages
in the liver (Kupffer cells), and macrophages of
lymph nodes, spleen, and bone marrow among
others. 61
Monocytes,,,

62
Monocyte,,,

63
 Monocyte,,,
Function of monocytes
 They are highly phagocytic cells.
 They are transformed to macrophages in
tissues & at the site of inflammation.
 They concentrate the antigens and
present them to the lymphocytes.

64
 Platelets
Platelets (thromboplastids) are small, disk-shaped, cell
fragments derived from megakaryocytes in the bone
marrow.
Non motile fragment surrounded by a plasma
membrane and containing granules
Small, colorless, non nucleated
Forms platelet plugs
Releases Chemicals necessary for blood clotting
Normal values:200,000-300,000/mm3 65
 Platelets,,,
Size: 2-4 µm and Life span is about 10 days

66
67