Topic 7 Connective Tissue

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Topic 7 Connective Tissue
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Literature

• http//www.lab.anhb.uwa.edu.au/mb140/
• (notes)
• http//www.anatomyatlases.org/MicroscopicAnatomy/M
  icroscopicAnatomy.shtml

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Connective Tissue
Connective tissue fills the spaces between organs
and tissues, and provides structural and
metabolic support for other tissues and organs.
Connective tissue is made up of cells and
extracellular matrix. The extracellular matrix
is made up of fibres in a protein and
polysaccharide matrix, secreted and organised by
cells in the extracellular matrix. Variations in
the composition of the extracellular matrix,
determines the properties of the connective
tissue. For example, if the matrix is calcified,
it can form bone or teeth. Specialised forms of
extracellular matrix also makes up tendons,
cartilage, and the cornea of the eye. General
connective tissue is either loose, or dense,
depending on the arrangment of the fibres. The
cells sit in a matrix made up of glycoproteins,
fibrous proteins and glycosoaminoglycans, which
have been secreted by the fibroblasts, and the
major component of the matrix is water.
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Development

• Mesoderm Neuroectoderm

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Mucous connective tissue

• Mucous connective tissue (or mucous tissue) is a
  type of connective tissue found during fetal
  development. It is composed mainly of ground
  substance with few cells or fibers. It can also
  be referred to a group of mucoproteins found in
  certain types of cysts (etc.), resembling mucus.
  It is most easily found as a component of
  Wharton's jelly.
• Mucous connective tissue forms the umbilical
  cord.
• The vitreous of the eyeball is a similar tissue.

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Mesenchyme, also called mesenchymal connective
tissue, is a type of undifferentiated loose
connective tissue that is derived mostly from
mesoderm, although some is derived from other
germ layers e.g. neural crest cells and thus
originates from the ectoderm. Most embryologists
use the term "mesenchyme" only for those cells
that develop from the mesoderm. The term
mesenchyme essentially refers to the morphology
of embryonic cells, however, they do persist as
stem cells into adulthood. Mesenchymal cells are
able to develop into the tissues of the lymphatic
and circulatory systems, as well as connective
tissues throughout the body, such as bone and
cartilage. Mesenchyme is characterized
morphologically by a prominent ground substance
matrix containing a loose aggregate of reticular
fibrils and unspecialized cells. Mesenchymal
cells can migrate easily.
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Classification

• 1. Connective tissue proper
• a. Loose Connective Tissue
• i. Areolar
• ii. Adipose
• iii. Reticular
• b. Dense Connective Tissue
• i. Dense regular
• ii. Dense irregular
• 2. Embryonic
• 3. Cartilage
• 4. Bone (osseous tissue)
• 5. Blood
• http//www.highlands.edu/academics/divisions/scipe
  /biology/labs/rome/histology.pdf

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• Connective tissues contain a large amount of
  non-living material referred to as the matrix.
• fibers
• ground substance
• Typically, this material is manufactured and
  secreted by the cells of the specific connective
  tissues.

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Fibers
Fiber Components
Location
Collagenous Fibers Elastic fibers Reticular
fibers
Alpha polypeptide chains elastic microfibril
elastin Type-III collagen
tendon, ligament, skin, cornea, cartilage, bone,
blood vessels, gut, and intervertebral
disc. extracellular matrix (blood
vessels) liver, bone marrow, lymphatic organs
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Ground substance

• Ground substance is found in all cavities and
  clefts between the fibres and cells of connective
  tissues. Water, salts and other low molecular
  substances are contained within the ground
  substance, but its main structural constituent
  are proteoglycans.Ground substance is soluble in
  most of the solvents used to prepare histological
  sections and therefore not visible in ordinary
  sections.
• Proteoglycans are responsible for the highly
  viscous character of the ground substance.
  Proteoglycans consist of proteins (5) and
  polysaccharide chains (95), which are
  covalently linked to each other. The
  polysaccharide chains belong to one of the five
  types of glycosaminoglycans.
• Hyaluronan (or hyaluronic acid) is the dominant
  glycosaminoglycan in connective tissues. MW
  1,000,000. Length of about 2.5 µm.
• Hyaluronan serves as a "backbone" for the
  assembly of other glycosaminoglycans in
  connective and skeletal tissue.

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• The large polyanionic carbohydrates of the
  glycosaminoglycans bind large amounts of water
  and cations.
• The bound water in the domains forms a medium for
  the diffusion of substances of low molecular
  weight such as gases, ions and small molecules,
  which can take the shortest route, for example,
  from capillaries to connective tissue cells.
• Large molecules are excluded from the domains and
  have to find their way through the spaces between
  domains.
• The restricted motility of larger molecules in
  the extracellular space inhibits the spread of
  microorganisms through the extracellular space. A
  typical bacterium ( 0.5 x 1 µm) is essentially
  immobilised in the meshwork formed by the
  domains.
• The pathogenicity of a bacterium is indeed to
  some extent determined by its ability to find its
  way through the mesh, and some of the more
  invasive types produce the enzyme hyaluronidase,
  which depolymerises hyaluronic acid.

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Connective Tissue Cells
Resident cells Immigrant cells
Specialised cells
Monocytes/ histocytes/ macrophages Plasmocytes Ma
st cells
Fibroblasts Adipocytes Pigment cells
Reticular cells (reticular tissue) Pericytes (bloo
d vessels) Shwan cells (nerve fibers) Glial
cells (CNS) Hondriocytes (cartillage) Osteocytes
(bone) Blood cells
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Fibroblasts

• Fibrocytes are the most common cell type in
  connective tissues. They are the "true"
  connective tissue cells.
• Flattened nuclei are visible in LM sections. The
  cytoplasm of inactive fibrocyte does not contain
  many organelles.
• Developed intermediate filaments vimentin.
• This situation changes if the fibrocytes are
  stimulated. Fibrocyte can be transformed into a
  fibroblast with large amounts of the organelles
  which are necessary for the synthesis and
  excretion of proteins.
• Fibrocytes are able to perform amoeboid movement.
• The terms fibrocyte and fibroblast refer here to
  the inactive and active cells respectively - at
  times you will see the two terms used as synonyms
  without regard for the state of activity of the
  cell.

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Fibroblasts
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Adipocytes

• Fat cells or adipocytes are fixed cells in loose
  connective tissue. Their main function is the
  storage of lipids. The cytoplasm only forms a
  very narrow rim around a large central lipid
  droplet. The flattened nucleus may be found in a
  slightly thickened part of this cytoplasmic rim -
  if it is present in the section, which may not be
  the case since the diameter of an adipocyte (up
  to 100 µm).
• A "starving" adipocyte may contain multiple small
  lipid droplets and gradually comes to resemble a
  fibrocyte.
• Lipid storage/mobilisation is under nervous
  (sympathetic) and hormonal (insulin) control.
  Adipocytes also have an endocrine function - they
  secrete the protein leptin which provides brain
  centers which regulate appetite with feedback
  about the bodies fat reserves.
• Adipocytes are very long-lived cells. Their
  number is determined by the number of
  preadipocytes (or lipoblast) generated during
  foetal and early postnatal development.

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Adipocytes
http//www.vh.org/Providers/Textbooks/MicroscopicA
natomy/
Each adipocyte is covered with basal membrane.
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Pigment cells
Melanocytes are melanin-producing cells located
in the bottom layer (the stratum basale) of the
skin's epidermis, the middle layer of the eye
(the uvea),1 the inner ear, meninges, bones,
and heart. Melanin is the pigment primarily
responsible for skin color.
http//en.wikipedia.org/wiki/Melanocyte
http//www.meddean.luc.edu/lumen
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• The color of the melanin is dark and it absorbs
  all the UV-B light and it blocks it from passing
  the skin layer.6
• Since the action spectrum of sunburn and
  melanogenesis are virtually identical, they are
  assumed to be induced by the same mechanism.7
  The agreement of the action spectrum with the
  absorption spectrum of DNA points towards the
  formation of cyclobutane pyrimidine dimers (CPDs)
  - direct DNA damage.

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• Once synthesised, melanin is contained in a
  special organelle called a melanosome and moved
  along arm-like structures called dendrites, so as
  to reach the keratinocytes. Melanosomes are
  vesicles which package the chemical inside a
  plasma membrane. The melanosomes are organized as
  a cap protecting the nucleus of the keratinocyte.

• http//www.vetmed.ufl.edu/sacs/histo/con01.htm

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Monocytes/histocytes/macrophages

• A histiocyte is a tissue macrophage or a
  dendritic cell (histio, diminutive of histo,
  meaning tissue, and cyte, meaning cell).
• Histiocytes are derived from the bone marrow by
  multiplication from a stem cell. The derived
  cells migrate from the bone marrow to the blood
  as monocytes. They circulate through the body and
  enter various organs, where they undergo
  differentiation into histiocytes, which are part
  of the mononuclear phagocytic system (MPS).

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• Histiocytes have common histological and
  immunophenotypical characteristics (demonstrated
  by immunostains). Their cytoplasm is eosinophilic
  and contains variable amounts of lysosomes. They
  bear membrane receptors for opsonins, such as IgG
  and the fragment C3b of complement. They express
  LCAs (leucocyte common antigens) CD45, CD14,
  CD33, and CD4 (also expressed by T Helper Cells).

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Macrophages and dendritic cells are derived from
common bone marrow precursor cells that have
undergone different differentiation (as
histiocytes) under the influence of various
environmental (tissue location) and growth
factors such as GM-CSF, TNF and IL-4. The various
categories of histocytes are distinguishable by
their morphology, phenotype, and
size. Macrophages are highly variable in size and
morphology, their cytoplasm contains numerous
acid phosphatase laden lysosomes - in relation to
their specialised phagocytic function. They
express CD68. Dendritic cells have an indented
(bean-shaped) nucleus and cytoplasm with thin
processes (dendritic). Their main activity is
antigen presentation they express Factor XIIIa,
CD1c, and Class II Human leukocyte antigens.
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A subset of cells differentiates into Langerhans
cells this maturation occurs in the squamous
epithelium, lymph nodes, spleen, and bronchiolar
epithelium. Langerhans cells are
antigen-presenting cells but have undergone
further differentiation. Skin Langerhans cells
express CD1a, as do cortical thymocytes (cells of
the cortex of the thymus gland). They also
express S-100, and their nucleus contains
tennis-racket like ultra-structural inclusions
called Birbeck granules.
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Mast cells
A mast cell (also known as mastocyte and
labrocyte1) is a resident cell of several types
of tissues and contains many granules rich in
histamine and heparin. Although best known for
their role in allergy and anaphylaxis, mast cells
play an important protective role as well, being
intimately involved in wound healing and defense
against pathogens.2 The mast cell is very
similar in both appearance and function to the
basophil, a type of white blood cell. However,
they are not the same, as they arise from
different cell lines.3
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Mast cells are very similar to basophil
granulocytes (a class of white blood cells) in
blood. Both are granulated cells that contain
histamine and heparin, an anticoagulant. Both
cells also release histamine upon binding to
immunoglobulin E.3 These similarities have led
many to speculate that mast cells are basophils
that have "homed in" on tissues. Furthermore they
share a common precursor in bone marrow
expressing the CD34 molecule. Basophils leave
the bone marrow already mature, whereas the mast
cell circulates in an immature form, only
maturing once in a tissue site. The site an
immature mast cell settles in probably determines
its precise characteristics.2
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Mast cells play a key role in the inflammatory
process. When activated, a mast cell rapidly
releases its characteristic granules and various
hormonal mediators into the interstitium. Mast
cells can be stimulated to degranulate by direct
injury (e.g. physical or chemical such as
opioids, alcohols, and certain antibiotics such
as polymyxins), cross-linking of Immunoglobulin
E (IgE) receptors, or by activated complement
proteins.2 Mast cells express a high-affinity
receptor (FceRI) for the Fc region of IgE, the
least-abundant member of the antibodies. This
receptor is of such high affinity that binding of
IgE molecules is essentially irreversible. As a
result, mast cells are coated with IgE, which is
produced by plasma cells (the antibody-producing
cells of the immune system). IgE molecules, like
all antibodies, are specific to one particular
antigen.
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http//en.wikipedia.org/wiki/Mast_cell
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Plasmocytes

• Plasma B cells (also known as plasma cells,
  plasmocytes, and effector B cells) are large B
  cells that have been exposed to antigen and
  produce and secrete large amounts of antibodies,
  which assist in the destruction of microbes by
  binding to them and making them easier targets
  for phagocytes and activation of the complement
  system. They are sometimes referred to as
  antibody factories. An electron micrograph of
  these cells reveals large amounts of rough
  endoplasmic reticulum, responsible for
  synthesizing the antibody, in the cell's
  cytoplasm. These are short lived cells and
  undergo apoptosis when the inciting agent that
  induced immune response is eliminated. This
  occurs because of cessation of continuous
  exposure to various colony-stimulating factors
  which is required for survival.

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http//www.vh.org/Providers/Textbooks/MicroscopicA
natomy/
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Loose connective tissue and dense connective
tissues These two tissues are distinguished
according to the relative amounts of fibres they
contain. Dense connective tissues are completely
dominated by fibres. They are subdivided
according to the spatial arrangement of the
fibres in the tissue. In dense irregular
connective tissue the fibres do not show a clear
orientation within the tissue but instead form a
densely woven three-dimensional network
(dermis). Dense connective tissue are if the
fibres run parallel to each other ( tendons,
ligaments and the fasciae and aponeuroses of
muscles). Loose connective tissue is relatively
cell rich, soft and compliant. It is also rich in
vessels and nerves. Loose connective tissue may
occur in some special variants mucous connective
tissue, reticular connective tissue and adipose
tissue.
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Loose connective tissue

• Loose connective tissue is a category of
  connective tissue which includes areolar tissue,
  reticular tissue, and adipose tissue. Loose
  connective tissue is the most common type of
  connective tissue in vertebrates. It holds organs
  in place and attaches epithelial tissue to other
  underlying tissues. It also surrounds the blood
  vessels and nerves. Cells called fibroblasts are
  widely dispersed in this tissue they are
  irregular branching cells that secrete strong
  fibrous proteins and proteoglycans as an
  extracellular matrix. The cells of this type of
  tissue are generally separated by quite some
  distance by a gel-like gelatinous substance
  primarily made up of collagenous and elastic
  fibers.
• Loose connective tissue is named based on the
  "hair weave" and type of its constituent fibers..
  

http//en.wikipedia.org/wiki/Loose_connective_tiss
ue
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Areolar tissue

• Areolar tissue (areol(-a) being Latin for a
  little open space) is a common type of connective
  tissue, also referred to as "loose connective
  tissue". It is strong enough to bind different
  tissue types together, yet soft enough to provide
  flexibility and cushioning.
• It exhibits interlacing,1 loosely organized
  fibers,2 abundant blood vessels, and
  significant empty space. Its fibers run in random
  directions and are mostly collagenous, but
  elastic and reticular fibers are also present.
  Areolar tissue is highly variable in appearance.
• In many serous membranes, it appears as a loose
  arrangement of collagenous and elastic fibers,
  scattered cells of various types abundant ground
  substance numerous blood vessels. In the skin
  and mucous membranes, it is more compact and
  sometimes difficult to distinguish from dense
  irregular connective tissue. It is the most
  widely distributed connective tissue type in
  vertebrates.

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The cells (dark spots within the tissue) are
called fibroblasts (fibro fiber, blast to make
or create). These are the cells responsible for
secreting the fibers present. The larger fibers
(typically pink) are called collagen fibers. The
small black fibers are elastic fibers.
Collectively, the fibers and the rest of the
substance surrounding the cells would be
referred to as the matrix.
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Reticular connective tissue

• Reticular connective tissue is a type of
  connective tissue.1 It has a network of
  reticular fibers, made of type III collagen.2
  Reticular fibers are not unique to reticular
  connective tissue, but only in this type are they
  dominant.3
• Reticular fibers are synthesized by special
  fibroblasts called reticular cells. The fibers
  are thin branching structures.
• Reticular connective tissue is named for the
  reticular fibers which are the main structural
  part of the tissue.
• The cells that make the reticular fibers are
  fibroblasts called reticular cells. Reticular
  connective tissue forms a scaffolding for other
  cells in several organs, such as lymph nodes and
  bone marrow.
• You will never see reticular connective tissue
  alone--there will always be other cells scattered
  among the reticular cells and reticular fibers.

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Dense irregular connective tissue

• Dense irregular connective tissue (DICT) consists
  of a somewhat dense arrangement of thick collagen
  type I fibers embedded, along with a smattering
  of fibroblasts, in an amorphous ground substance.
  
• Characteristically, dense irregular connective
  tissue differs from loose connective tissue in
  three basic ways The most abundant part of dense
  irregular connective tissue are the collagen type
  I fibers, not the amorphous ground substance.
• The extracellular fibers of DCT are nearly
  entirely collagen type I fibers.
• The cells of DCT are less abundant and are
  virtually all fibroblasts few other cells, if
  any, are present.
• Dense irregular connective tissue has an
  irregular, somewhat disorderly, dense weave of
  thick collagen type I fibers, with bundles of
  fibers oriented in all directions. With its high
  tensile strength, dense irregular connective
  tissue effectively binds various tissues together
  to form organs and passively translates
  mechanical forces in all directions without
  tearing. Unlike loose connective tissue, it is
  NOT a designed to be a theatre of inflammation.
• Dense irregular connective tissue is found in
  several locations the dermis of the skin, the
  walls of large tubular organs, such as the
  alimentary canal, in glandular tissue, and in
  organ capsules.

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Dense regular connective tissue

• Tendons
• Ligaments
• Fascia
• Elastic tissue
• Aorta

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Tendons
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http//www.umdnj.edu/khochtah/ligament.html
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http//education.vetmed.vt.edu/Curriculum/ VM8054/
Labs/Lab12b/EXAMPLES/Exlasart.htm