CONNECTIVE TISSUES I. Introduction A ... - Faculty.rmc.edu

CONNECTIVE TISSUES
I. Introduction
A. Connective tissue (CT) is characterized by extensive extracellular matrix and widely spaced
cells.
1. Typical CT contains at least one cell type which synthesizes and secretes the extensive
extracellular materials, both fibrous and amorphous, which form the matrix around the
cells.
2. Amorphous extracellular material fills most of the spaces between the cells and fibers in
most types of CT. These regions may appear empty in routine light microscopic
preparations.
3. Loose connective tissues contain many types of immune and paraimmune system cells
in addition to the cells which form and maintain the matrix.
B. A continuum of fibrous connective tissues exists from the looser tissues (mostly cells with
small fibers and low mechanical strength) to denser tissues (scattered cells, densely packed
large fibers, and relatively high mechanical strength). Cartilage and bone are dense
connective tissues with small fibers and highly developed amorphous components.
C. Connective tissue, depending on type, carries out a number of functions which are related to
the amount and type of extracellular materials in the matrix of the connective tissue.
1. Loose fibrous connective tissues are the stromal tissues of most internal organs and
provide a flexible framework which holds the other tissues of the organ together without
interfering with their functions.
2. Adipose connective tissue provides padding for organs.
3. Dense irregular fibrous connective tissue in the dermis provides most of the mechanical
strength for the skin which covers the surface of the body.
4. Dense fibrous connective tissues, cartilage, and bone provide overall support for the
vertebrate body.
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II.
Components of Connective Tissue
A. Extracellular matrix (ECM) may include fibers and amorphous materials.
1. Fibrous Components
a. Collagenous Fibers (Table 6.2 and Figs. 6.5 - 6.8)
(1) Collagen fibers in fibrous connective tissue and bone are primarily Type I
collagen. Collagen fibers in cartilage are Type II collagen.
(a) Typical fibrous connective tissue collagen fibers consist of bundles of Type
I collagen fibrils. The fibrils measure 20 to 200 nanometers in diameter
and are cross-banded in a complex pattern which repeats every 68 nm
(see Fig. 6.7).
(b) Typical collagen fibers are clearly recognizable in TEM preparations
because of the cross-banding pattern. Collagen fibers are acidophilic in
routine LM preparations and can be specifically stained by a variety of
techniques.
(c) Collagen fibers are "bendable" but not "stretchable" (steel cable-like
properties) and therefore limit stretching of a tissue in the direction in which
the fibers run. The larger the bundles of fibrils, the more restricted the
stretch of the tissue.
(2) Reticular fibers (usually Type III collagen) (Fig. 6.12)
(a) Reticular fibers are small intertwining bundles or single collagen fibrils
(usually about 20 nanometers in diameter) which form a meshwork.
(b) Reticular fibers can be recognized in TEM by the small bundles, the more
uniform diameter of the fibrils, and the relative lack of cross-banding.
Reticular fibers are not visible in routine LM preparations, but are easily
visible by LM following silver staining.
(c) Reticular fibers form the reticular layer in basement membranes and are
important in the stroma of many glands.
b. Elastic Fibers (Fig. 6.13 - 6.15)
(1) Elastic fibers are a combination of amorphous elastin plus a microfibrillar
component. In the absence of the microfibrillar component, elastin sheets or
laminae are formed.
(2) Elastic fibers can be recognized by TEM because of their structure. Elastic
fibers are frequently slightly more acidophilic than collagen fibers in routine LM
preparations and can be identified by specific staining (resorcin-fuchsin, etc.).
(3) Elastic fibers are highly elastic (stretchable, return to original length when
released).
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2. Amorphous Components lack recognizable structure in either TEM or LM. Amorphous
components were referred to in the past as "ground substance". Various amorphous
components may be complexed with each other and with fibrous components. This
material may complex with minerals to form the rigid ECM found in bony tissue.
a. Amorphous components of ECM may include many types of chemicals.
(1) Proteins of many types occur in ECM.
(2) Glycoproteins (proteins with added oligosaccharide groups)(Table 6.5, Fig.
6.18) which occur in relatively large amounts as amorphous components in
ECM include fibronectin, laminin, some types of collagen, etc. Fibronectin links
different ECM components and allows attachment of cells to extracellular
matrix. Laminin serves similar functions in basal lamina.
(3) Glycosaminoglycans (GAGs) (Table 6.3, Fig. 6.16) are polysaccharides
consisting of disaccharide units, at least one of which is sulfated or contains a
carboxylic acid side chain. The acidic groups result in highly acidic
characteristics for the entire GAG, making them highly basophilic. Most GAGs
have a molecular weight of about 10,000-50,000, but hyaluronic acid may have
a molecular weight of 1 million.
(4) Proteoglycans (Figs. 6.16, 6.17) consist of GAGs assembled on a core protein
to form a very large molecule (about 2 million Dalton in some cases).
(5) Proteoglycan Aggregates (Fig. 6.16, 6.17) usually consists of proteoglycans
assembled onto a hyaluronic acid molecule to form a complex "supermolecule"
which may have a volume larger than a mitochondrion.
3. Tissue Fluid is the extracellular fluid in connective tissue as well as in other tissues.
Since tissue fluid is formed by exchange with blood plasma across endothelial layers,
tissue fluid is approximately equal to blood plasma minus most of the plasma proteins.
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B. Cells in connective tissues
1. Resident or permanent cells
a. Matrix-forming and maintaining cells are responsible for the synthesis and
secretion of the fibrous and amorphous components of the ECM of the different
types of CT.
(1) Mesenchyme cells
(a) True mesenchyme cells occur only in embryos and are derived from
mesoderm or from neural crest. Mesenchyme cells can differentiate into all
types of adult matrix forming cells.
(b) Mesenchyme cells are spindle-shaped or stellate with a large nucleus
(usually with distinct nucleolus) and relatively little cytoplasm, often forming
thin processes.
(c) Mesenchyme cells produce primarily GAGs and proteoglycans, especially
hyaluronic acid.
(d) Cells with similar properties found in adult CT are called mesenchymal
stem cells and appear to function in tissue repair.
(2) Fibroblasts (and fibrocytes)(Figs. 6.19, 6.20, 6.8)
(a) Fibroblasts occur in all adult fibrous connective tissues.
(b) Fibroblasts are large, flattened (spindle-shaped in sections) cells with oval
or elongated nuclei containing both euchromatin and heterochromatin and
usually containing an obvious nucleolus. Fibrocytes have flattened
heterochromatic nuclei. Fibroblast cytoplasm is slightly basophilic (due to
extensive rER) if the cell is very active and slightly acidophilic if the cell is
inactive. Fibroblasts typically have long thin cytoplasmic processes which
are visible with TEM.
(c) Fibroblasts secrete collagen fiber bundles, reticular fibers, elastics fibers,
GAGs, and glycoproteins.
(d) Myofibroblasts are fibroblastic cells which contain elaborated actin filament
bundles and are therefore contractile. Myofibroblasts appear to be
important in wound closure.
(3) Reticular cells (Plate 34)
(a) Reticular cells occur only in reticular connective tissue. Reticular
connective tissue is usually the stromal component of lymphoid tissue.
(b) Reticular cells are stellate cells with long cellular processes which make
contact with other cells. The processes of reticular cells surround the
reticular fibers in the ECM of reticular CT. Reticular cells have large nuclei
with distinct nucleoli.
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(c) Reticular cells secrete reticular fibers and GAGs. Some reticular cells are
probably also phagocytic.
(4) Chondroblasts and chondrocytes (Figs. 7.4 - 7.7, Plate 7)
(a) Chondroblasts and chondrocytes occur only in cartilage.
(b) Chondroblasts and healthy chondrocytes are large spherical to oval cells
with basophilic cytoplasm and oval nuclei containing distinct nucleoli.
Degenerating or poorly preserved chondrocytes frequently appear
shrunken and contain small predominately heterochromatic nuclei.
(c) Chondroblasts and chondrocytes may synthesize and secrete collagen
(which forms small reticular fiber-like arrays in most cartilage or collagen
fiber bundles in fibrocartilage), elastin (which forms visible elastic fibers in
elastic cartilage), GAGs, and proteoglycans.
(5) Osteoblasts (Figs. 8.7 - 8.9)
(a) Osteoblasts are found only on or near growing surfaces of bone tissue.
(b) Osteoblasts are roughly cuboidal cells with spherical to oval nuclei (often
with visible nucleoli) and basophilic cytoplasm. Osteoblasts become
stellate with fine processes when they are surrounded by bone matrix.
(c) Osteoblasts synthesize and secrete the organic components of bone
matrix, consisting of collagen (which forms fine collagen fiber bundles),
GAGs, glycoproteins, and proteoglycans. Osteoblasts also pinch off from
their surfaces the alkaline phosphatase-rich matrix vesicles which initiate
mineralization of immature bone.
(6) Osteocytes (Fig. 8.10)
(a) Osteocytes are found only in formed bone matrix.
(b) Osteocytes are stellate (with thin processes) cells with spherical to oval
nuclei and weakly basophilic or unstained cytoplasm. Osteocytes are very
poorly preserved in most preparations.
(c) Osteocytes normally "maintain" bone matrix, but they are capable of small
amounts of net synthesis or net resorption of bone matrix.
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. Matrix-removing cells
(1) Osteoclasts (Figs. 8.12 - 8.15)
(a) Osteoclasts occur on and near surfaces where bone matrix is being resorbed.
(b) Osteoclasts are large multinucleate cells with acidophilic cytoplasm containing
numerous acid phosphatase- rich lysosomes. The surface of the osteoclast
next to the bone matrix has numerous infoldings in the plasma membrane
which form a ruffled border.
(c) Osteoclasts resorb bone matrix by releasing lysosomes and organic acids onto
the bone matrix surface. Osteoclasts can also break down cartilage matrix
trapped in bone matrix during endochondrial bone formation. Osteoclasts can
be formed from monocytes and are therefore related to macrophages.
c. Storage cells
(1) White fat cells (white adipocytes) (Figs 9.1 - 9.3)
(a) White adipocytes occur in loose connective tissues and are the dominant cells
in white adipose connective tissue.
(b) White adipocytes are large spherical cells with a flattened eccentric nucleus in a
thin rim of cytoplasm surrounding a single large central fat droplet.
(c) White adipocytes are the major fat storage cells in adult humans.
(d) White adipocytes develop from the same precursor cells that give rise to
fibroblasts, but the control of their development is unclear.
(2) Brown fat cells (brown adipocytes) (Figs 9.1, 9.4)
(a) Brown adipocytes occur in brown fat deposits in embryonic and neonatal
humans but are rare in adult humans.
(b) Brown adipocytes are spherical cells (smaller than white fat cells) containing
spherical eccentric nuclei, multiple small fat droplets, and numerous
mitochondria.
(c) Brown adipocytes are capable of rapid heat generation.
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2. Transient or migratory cells
a. Macrophages (Fig. 6.22)
(1) Macrophages occur in most loose and moderately dense fibrous connective
tissues. Some macrophages may be relatively long-term residents of
connective tissues while other macrophages are clearly migratory.
(2) Two types of macrophages are frequently described, but the relationships
between these morphological categories and functional categories are unclear.
Most macrophages are probably quite variable in morphology and are capable
of rapid changes in function in response to chemical signals.
(a) "Fixed" macrophages are associated with CT fibers and therefore tend to
have a more elongated shape.
(b) Free macrophages are not associated with CT fibers and tend to be more
oval in shape.
(3) Macrophages usually appear in routine LM preparations as flattened cells
(slightly smaller than fibroblasts) with football- shaped to kidney bean-shaped
nuclei containing both euchromatin and heterochromatin.
Macrophage nuclei are usually slightly smaller and slightly darker staining
than fibroblast nuclei in the same preparation. Macrophages are difficult to
distinguish from fibroblasts, so positive identification depends on detection of
specific cell surface markers which are unique to macrophages.
Newly developed macrophages have weakly acidophilic cytoplasm containing
lysosomal granules (acid phosphatase positive). Activated macrophages
contain cytoplasm filled with obvious granules of undigested material. Most
macrophages have elongated processes which are not obvious by LM but
which are seen with TEM and SEM.
(4) Macrophages are phagocytic cells derived from monocytes. Macrophages are
important in removal of debris from connective tissues, in stimulating immune
responses, and in defense against some types of bacteria and some types of
tumor cells.
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. Lymphocytes (Fig. 10.11, Plate 4, Fig. 4)
(1) Lymphocytes occur in loose connective tissues and are the most abundant cell
type in lymphoid tissue.
(2) Lymphocytes have small, heterochromatic, spherical nuclei surrounded by very
thin rims of cytoplasm.
(3) Lymphocytes include several functional categories of immune response and
regulatory cells which cannot be distinguished by routine LM.
(a) T lymphocytes are responsible for cell-mediated immunity.
(b) B lymphocytes develop into plasma cells which secrete antibodies.
(c) Natural killer cells kill virus-infected cells and some types of cancer cells.
c. Plasma cells (Fig. 6.25, Plate 4, Fig. 4)
(1) Plasma cells occur in lymphoid tissues and in loose connective tissues.
Plasma cells are especially numerous in loose connective tissue below the
luminal epithelium in the digestive, respiratory, and reproductive tracts.
(2) Plasma cells are large lymphocytes with eccentric spherical or oval nuclei
containing central euchromatin and peripheral heterochromatin ("clock face
nucleus"). The cytoplasm is strongly basophilic due to abundant rough
endoplasmic reticulum and contains a prominent Golgi apparatus near the
center of the cell.
(3) Plasma cells are active antibody synthesizing and secreting cells derived from
B lymphocytes.
d. Neutrophils (Figs. 10.6 - 10.8)
(1) Neutrophils occur in most loose connective tissues.
(2) Neutrophils contain heavily heterochromatic nuclei divided into 3 to 5 lobes.
Their cytoplasm contains numerous secretory granules which are usually very
weakly acidophilic.
(3) Neutrophils are antibacterial cells and accumulate in sites of bacterial
infections.
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e. Eosinophils (Fig. 10.9)
3. Other cells
(1) Eosinophils occur in small numbers in most loose connective tissues.
(2) Eosinophils have heterochromatic bilobed nuclei and cytoplasm packed with
acidophilic granules which are modified lysosomes.
(3) Eosinophils accumulate around parasitic infections and in areas of allergic
reactions. Eosinophils damage large parasites (like nematodes) by secreting
their modified lysosomes onto the surface of the parasite. Eosinophils
phagocytize antigen-antibody complexes and inactivate several types of
inflammatory molecules released by mast cells.
a. Mast cells (Fig. 6.23)
(1) Mast cells occur in most loose and moderately dense connective tissues and
are most numerous near small blood vessels.
(2) Mast cells are large spherical to oval cells with a spherical nucleus containing
mixed euchromatin and heterochromatin. Mast cell cytoplasm is filled with
numerous basophilic granules.
(3) Mast cell cytoplasmic granules contain approximately 30 different components,
including histamine and heparin (and serotonin in rodents), which increase
permeability of blood vessel walls. Mast cell granules are released in response
to antigen binding to antibodies in receptors on the mast cell surface.
b. Pericytes or perivascular cells (Fig. 6.24)
(1) Pericytes are observed outside the endothelium of capillaries, venules, and
small veins, primarily in loose connective tissues. Pericytes typically share a
continuous basal lamina with adjacent endothelial cells. The basal lamina runs
between the pericyte and the endothelium but also separates the pericyte from
the surrounding connective tissue.
(2) Pericytes are flattened cells with oval nuclei and little cytoplasm.
(3) The functions of pericytes are unclear, but they may be mesenchyme-like cells
which can differentiate into other types of CT cells or they may be muscle-like
cells which alter capillary permeability. Perivascular cells may be one source of
new capillary smooth muscle cells during outgrowth of blood vessels.
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III. COMPOSITION OF DIFFERENT TYPES OF CONNECTIVE TISSUE
Type Cellular Extracellular
Components
Components
Loose Connective Tissues
Mesenchymal Mesenchyme GAGs (e.g.,
CT Cells hyaluronic acid)
Mucous Fibroblasts Very Fine Collagen fibers
CT
GAGs
Loose FECT Fibroblasts Small Collagen fibers
(FibroElastic Macrophages Small Elastic fibers
Connective Adipocytes Reticular fibers
Tissue) Mast Cells GAGs
Neutrophils
proteoglycans
Eosinophils
Lymphocytes
Plasma cells
Perivascular cells
Adipose Adipocytes Reticular fibers
CT (white and/or GAGs
brown)
proteoglycans
Reticular Reticular cells Reticular fibers
CT Lymphocytes GAGs
Plasma cells
proteoglycans
Macrophages
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Type Cellular Extracellular
Components
Components
Moderately Dense or Intermediate Connective Tissues
Moderately Fibroblasts Collagen fibers
Dense or Macrophages Elastic fibers
Intermediate
Reticular Fibers
FECT
GAGs
Dense Fibrous Connective Tissues
Dense Fibroblasts Very Large Collagen fibers
Irregular Macrophages Elastic fibers
FECT
Reticular fibers
GAGs
Dense Fibroblasts Collagen fibers
Regular
Elastic fibers
FECT
GAGs
Dense Fibroblasts Collagen fibers
Regular Fibrocytes GAGs
Collagenous
CT
Dense Fibroblasts Elastic fibers
Regular
GAGs
Elastic
CT
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Type Cellular Extracellular
Components
Components
Cartilage
Hyaline Chondroblasts Very Fine Collagen fibers
Cartilage Chondrocytes GAGs
Proteoglycans
Elastic Chondroblasts Fine Elastic fibers
Cartilage Chondrocytes Very Fine Collagen fibers
GAGs
Proteoglycans
Fibro- Chondrocytes Large Collagen fibers
Cartilage
GAGs
Bone
Woven Osteoblasts Collagen fibers
Bone Osteocytes GAGs
(Immature Osteoclasts Proteoglycans
Bone)
Glycoproteins
Hydroxyapatite
Ca 2+ 10(PO 3- 3 ) 6 (OH - ) 2
Spongy Osteoblasts Collagen fibers
Bone Osteocytes GAGs
(Cancellous Osteoclasts Proteoglycans
Bone)
Glycoproteins
Hydroxyapatite
Ca 2+ 10(PO 3- 3 ) 6 (OH - ) 2
Compact Osteoblasts Collagen fibers
Bone Osteocytes GAGs
Osteoclasts
Proteoglycans
Glycoproteins
Hydroxyapatite
Ca 2+ 10(PO 3- 3 ) 6 (OH - ) 2
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IV. Classifying Fibroelastic Connective Tissue
A. Loose fibroelastic connective tissue (FECT)
1. The ECM usually contains relatively small diameter collagen fibers. Abundant
amorphous extracellular material frequently keeps the fibers separated. The diameter of
collagen fiber bundles is typically smaller than the diameter of the nuclei of the
fibroblasts in the tissue.
2. A wide diversity of cell types occur in the tissue.
a. Fibroblasts are usually present and responsible for production and maintenance of
ECM
b. Blood and immune system cells (granulocytes, lymphocytes, plasma cells), and
macrophages are common in most loose FECTs.
c. White adipose cells are frequently present.
3. Cells are more numerous than in more dense FECT. In very loose FECT the cells may
occupy more volume than the fibers.
B. Moderately dense FECT
1. Fibers are intermediate in size, arrangement and packing relative to loose and dense
FECT.
2. Cells are intermediate in diversity and number relative to loose and dense FECT.
Fibroblasts and macrophages are usually the only abundant cell types.
C. Dense FECT
1. Extensive arrays of large collagen fibers fill most of the volume of the tissue. Collagen
fiber bundle diameters are typically much larger than the diameter of the cells.
2. Fibroblasts are usually the most frequently encountered cell type.
3. Fewer cells per unit volume are present (relative to moderately dense FECT).
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