Ch 5: Connective Tissue Flashcards
Connective Tissue serves what purpose?
: provides supportive and connective framework for all tissues in body
CLASSIFICATION OF CONNECTION TISSUE:
what are the 4 types?
1. Connective Tissue Proper
– Loose connective tissue
*Areolar
* Adipose
* Reticular
– Dense connective tissue
* Regular
* Irregular
* Elastic
- *2. Cartilage**
- Hyaline cartilage
- Elastic cartilage
- Fibrocartilage
- *3. Bone Tissue**
- Compact bone
- Spongy bone
4. Blood
Which are considered specialized connective tissue?
Adipose
Blood
Bone
cartilage
hemoportic
lymphatic
Define Mucous tissue / the umbilical cord
most of the connective tissue between the vessels consists of collagen fibers.
- Between the collagen fibers are small cells staining red, they are fibrocytes and fibroblasts.
- white space is ground substance.
Loose Connective Tissue
characterized by a loose irregular arrangement of connective tissue fibers and
abundant ground substance. Collagen fibers, fibroblasts(most numerous), mast cells and macrophages
predominate in loose connective tissue.
- thickest lighter staining strands are
collagen fibers.
- thinner darker staining fibers is elastic
fibers.
- fibroblasts lie along the length of collagen
fibers.
Stain: H&
Dense Connective tissue / Tendon
- Dense regular connective tissue is present in ligaments and tendons.
- consists of long collagen fibers (typically type I)
- between the densely packed collagen fibers are flatten nuclei of
- *fibroblasts.**
Adipose Tissue:
Adipose cells are closely packed and separated by thin strips of connective tissue septa in which are found compressed fibroblasts, arterioles, venules, nerves and capillaries
(non is visible in slide).
- the adipose cell nuclei are located peripherally. (not visible in slide).
- adipocytes are derived from lipoblasts that are derived from mesenchymal cells.
- lipid droplets are present inside the adipose cell.
Unlike the other tissue types (epithelium, muscle, and nerve), which consist mainly of cells, what makes up most of Connective tissue?
composed of fibroblasts and other cells that make up the
extracellular matrix (ECM) of various protein fibers,
all of which are surrounded by watery ground substance
Where does Connective Tissue come from?
Mesenchyme, which are undifferentiated cells with large nuclei, with prominent nucleoli and fine chromatin and are spindle shaped.
What do Fibroblast do in Connective Tissue? other cells found in here, such as macrophages , plasma cells , and mast cells.
originate locally from mesenchymal cells and are permanent residents of connective tissue; and are the most common cells in connective tissue, produce and maintain most of the tissue’s extracellular components. Fibroblasts synthesize and secrete collagen (the most abundant protein of the body) and elastin, which form large fibers, as well as the GAGs, proteoglycans, and multi adhesive glycoproteins that comprise the ground substance.
What else does Fibroblast do for connective tissues?
They are targets of many families of proteins called growth factors that influence cell growth and differentiation.
-involved in wound healing, sometimes called myofibroblasts, have a well-developed contractile function and are enriched with a form of actin also found in smooth muscle cells.
Adipocytes
These large,
mesenchymally derived cells are specialized for cytoplasmic
storage of lipid as neutral fats, or less commonly for the production
of heat. The large deposits of fat in the cells of adipose
connective tissue also serve to cushion and insulate
the skin and other organs.
Macrophages & the Mononuclear
Phagocyte System
phagocytic ability and specialize in turnover of protein fibers
and removal of dead cells, tissue debris, or other particulate
material.
A typical macrophage measures between
10 and 30 μm in diameter and has an eccentrically located,
oval or kidney-shaped nucleus.
Macrophages are also secretory cells producing an
array of substances, including various enzymes for
ECM breakdown and various growth factors or cytokines
that help regulate immune cells and reparative
functions.
What else does Macrophages able to do in the system?
Macrophages derive from bone marrow precursor cells
that divide, producing monocytes that circulate in the blood.
These cells cross the epithelial wall of venules to penetrate connective
tissue, where they differentiate further, mature, and
acquire the morphologic features of phagocytic cells. Therefore,
monocytes and macrophages are the same cell at different
stages of maturation.
Mast cells are
oval or irregularly shaped connective tissue cells,
between 7 and 20 μm in diameter, whose cytoplasm is filled with
basophilic secretory granules.
Because of their high content of
acidic radicals in their sulfated GAGs, mast cell granules display
metachromasia, which means that they can change the color of
some basic dyes
Mast cells release numerous bioactive substances with the roles in the inflammatory response. Below are 6 of them.
Heparin, a sulfated GAG that acts locally as an anticoagulant
■■ Histamine, which promotes increased vascular permeability
and smooth muscle contraction
■■ Serine proteases, which activate various mediators of
inflammation
■■ Eosinophil and neutrophil chemotactic factors,
which attract those leukocytes
■■ Cytokines, polypeptides directing activities of leukocytes
and other cells of the immune system
■■ Phospholipid precursors for conversion to prostaglandins,
leukotrienes, and other important lipid mediators
of the inflammatory response.
mast cells are especially numerous near small blood vessels in the skin and
mesenteries (perivascular mast cells) and in the tissue that lines
digestive and respiratory tracts.
mast cells place themselves strategically
to function as sentinels detecting invasion by microorganisms.
Mast cells originate from progenitor cells in the bone
marrow. The progenitor cells circulate in the blood, cross
the wall of venules and capillaries, and penetrate connective
tissues, where they differentiate.
Release of certain chemical mediators stored in mast cells
also promotes the allergic reactions, also known as
immediate
hypersensitivity reactionsbecause they occur within a
few minutes after the appearance of an antigen in an individual
previously sensitized to the same or a very similar antigen.
Plasma cells are:
are B-lymphocyte–derived, antibody-producing
cells.
These large, ovoid cells have basophilic cytoplasm due
to their richness in RER
They have a clock like face.
They are also specific antibodies.
White blood cells: Leukocytes
Leukocytes, or white blood cells, make up
a population of wandering cells in connective tissue. They
leave blood by migrating between the endothelial cells lining
venules to enter connective tissue by a process called diapedesis.
The fibrous components of connective tissue are elongated
structures formed from proteins that polymerize after secretion
from fibroblasts: Name them:
collagen, reticular, and elastic fibers.
Describe the realtion of the 3 main types of fibers.
Collagen and
reticular fibers are both formed by proteins of the collagen family,
and elastic fibers are composed mainly of the protein elastin.
These fibers are distributed unequally among the different types
of connective tissue, with the predominant fiber type usually
responsible for conferring specific tissue properties.
Collagen is a key element in all connective tissue as well as epithelial basement membranes and the external laminae of muscle and nerve cells.
It is also the most abundant protein.
They constitute a family of proteins selected during
evolution for their ability to form a variety of extracellular
structures. The various fibers, sheets, and networks made
of collagens are all extremely strong and resistant to normal
shearing and tearing forces.
Fibrillar collagens:
Collagen type I, the most abundant and
widely distributed collagen, forms large, eosinophilic
bundles usually called collagen fibers. These often
densely fill the connective tissue, forming structures such
as tendons, organ capsules, and dermis.
Sheet-forming collagens such as type IV collagen
have subunits produced by epithelial cells and are the
major structural proteins of external laminae and the
basal lamina in all epithelia.
Linking/anchoring collagens
are short collagens that
link fibrillar collagens to one another (forming larger
fibers) and to other components of the ECM. Type VII
collagen binds type IV collagen and anchors the basal
lamina to the underlying reticular lamina in basement
membranes.
Collagen synthesis occurs in many cell types but is a
specialty of cells that produce the various kinds of connective
tissue. Where is the intial part of them made?
The initial procollagen α chains are made in the cells’
abundant RER.
Keloids:
is a local swelling caused by abnormally large
amounts of collagen that form in scars of the skin.
Keloids occur most often in individuals of African descent
and can be a troublesome clinical problem to manage.
Not only can they be disfiguring, but excision is almost
always followed by recurrence.
Key steps in Collagen formation:
- Hydroxylase
- Procollagen peptidase
- Lysyl Oxidase
- Collagenases
Hydroxylase enzymes in the ER cisternae add hydroxyl
groups to some prolines and lysines in important reactions
that require O2, Fe2+, and ascorbic acid (vitamin C)
as cofactors.
Outside the cell, specific proteases called procollagen
peptidases remove the terminal globular peptides, converting
the procollagen molecules to collagen molecules.
Fibrillar structure is reinforced and disassembly is prevented
by the formation of covalent cross-links between
the collagen molecules, a process catalyzed by the enzyme
lysyl oxidase.
Degradation is
initiated by specific enzymes called collagenases, which are
members of an enzyme class called matrix metalloproteinases
(MMPs). Collagenases clip collagen fibrils or sheets in
such a way that they are then susceptible to further degradation
by nonspecific proteases.
Reticular Fibers
Found in delicate connective tissue of many organs, they consist mainly of collagen type III. This collagen forms an extensive network (reticulum) of extremely thin heavily glycosylated fibers. Reticular fibers are seldom
visible in hematoxylin and eosin. They are termed argyrophilic.
Elastic Fibers
thinner than the type I collagen fibers
and form sparse networks interspersed with collagen bundles in many organs, particularly those subject to much bending
or stretching.
In
the wall of large blood vessels, especially arteries, elastin also
occurs as fenestrated sheets called
elastic lamellae
Elastic fibers (and lamellae) are a composite of
fibrillin microfibrils embedded in a larger mass of cross-linked
elastin. Both components are secreted from fibroblasts (and
smooth muscle cells in vascular walls) and produce elastic
fibers in a stepwise manner.
Elastin molecules are rich in….
glycine, proline, and lysine, giving much of the protein a
random-coil conformation.
What makes up the so called “Ground Substance” of the ECM.
highly hydrated (with
much bound water), transparent, complex mixture of macromolecules,
principally of three classes: glycosaminoglycans
(GAGs), proteoglycans, and multiadhesive glycoproteins.
It fills the space between cells and fibers in connective
tissue and, because it is viscous, acts as both a lubricant and a
barrier to the penetration of invaders.
What are GAGS?
(also called mucopolysaccharides) are long
polysaccharides consisting of repeating disaccharide units,
usually a uronic acid and a hexosamine. The hexosamine can
be glucosamine or galactosamine, and the uronic acid can
be glucuronic or iduronic acid. The largest, almost unique,
and most ubiquitous GAG is hyaluronic acid (made by hyaluronate synthase)
What are some of the other smaller GAGS?
The four major GAGs
found in proteoglycans are dermatan sulfate, chondroitin
sulfates, keratan sulfate, and heparan sulfate, all of which
have different disaccharide units and tissue distributions. They are also hydrophilic.
Proteoglycans are composed of a core protein to which
are covalently attached various numbers and combinations of
the sulfated GAGs. distinguished by their diversity, like Decorin, Syndecan, and Aggrecan
Decorin has few GAG
side chains and binds fibrils of type I collagen. Cell surface
proteoglycans such as syndecan have transmembrane core proteins and serve as additional attachments of the cell to the
ECM. One of the best known proteoglycans, aggrecan, is very
large (250 kDa), with a core protein bearing many chondroitin
sulfate and keratan sulfate chains.
Both matrix-
linked
and cell surface proteoglycans also bind and sequester certain
signaling proteins, for example fibroblast growth factor (FGF).
Degradation of proteoglycans during the early phase of tissue
repair releases these stored growth factors that then stimulate
new cell growth and ECM synthesis.
The third class of ground substance components, the **multiadhesive glycoproteins.**
Which all have multiple binding
sites for cell surface receptors (integrins) and for other matrix
macromolecules. The adhesive glycoproteins are very large
molecules with branched oligosaccharide chains and have
important roles in the adhesion of cells to their substrate.
The large (200-400 kDa), trimeric, cross-shaped glycoprotein **laminin**
provides adhesion for epithelial and other cells, with
binding sites for integrins, type IV collagen, and specific proteoglycans.
Glycoprotein Fibronectin
synthesized largely by fibroblasts, is a 235-270 kDa dimeric
molecule, has binding sites for collagens and certain GAGs,
and forms insoluble fibrillar networks throughout connective
tissue.
The integrin family of integral membrane proteins act as
matrix receptors for specific sequences on laminin, fibronectin,
some collagens, and certain other ECM proteins….
Integrins bind their ligands in the ECM with relatively low affinity,
allowing cells to explore their environment without losing
attachment to it or becoming glued to it.
structures called focal adhesions
Integrins and other proteins associated with intermediate
filaments form the hemidesmosomes of epithelia
clustered integrin-microfilament complexes in fibroblasts
form structures. This type of adhesive
junction is typically present at the ends of actin filaments bundled
by α-actinin as cytoplasmic stress fibers
Outside of Ground substance, what is theother liquid space called?
In addition to the hydrated ground substance of connective
tissue, a small quantity of free interstitial fluid, with ion
composition similar to that of blood plasma, is also present.
Interstitial fluid contains plasma proteins of low molecular
Two forces act on the water in capillaries
The hydrostatic pressure of the blood caused by the
pumping action of the heart, which forces water out
across the capillary wall
■■ The colloid osmotic pressure produced by plasma
proteins such as albumin, which draws water back into
the capillaries
In adults we have 2 connective tissue types, Loose and Dense:
It comprises a thick layer (the lamina propria) beneath the epithelial
lining of the digestive system and fills the spaces between muscle
and nerve fibers. thin layers of loose connective tissue surround most small blood vessels of the body. Also called areolar tissue
Dense connective tissue is adapted to offer stress resistance
and protection. Has more collagen fibers over ground subtance.
In Dense irregular connective
tissue
bundles of collagen fibers appear randomly interwoven,
with no definite orientation. The collagen fibers form a tough
three-dimensional network, providing resistance to stress
from all directions.
Often these are found closely associated with loose connective tissue, with the
two types frequently grading into each other and making distinctions
between them somewhat arbitrary
type I collagen bundles of dense regular connective
tissue
are arranged according to a definite pattern,
with fibers and fibroblasts aligned in parallel for resistance to
prolonged or repeated stresses exerted in the same direction.
Examples: tendons, ligaments.
In some tendons, the dense irregular connective
tissue sheath is covered by flattened synovial cells of
mesenchymal origin, which produce lubricant fluid
However, tendons are poorly vascularized, as to why it takes so long to heal.
In reticular tissue fibers of type III collagen
form a delicate 3D network that supports various types of
cells. The fibrous network of this specialized connective tissue
is produced by modified fibroblasts called reticular cells
that remain associated with and partially covering the fibers.
Mucoid (or mucous) connective tissue: which is another embryonic type of connective tissue, found mostley in fetal organs.
Mucoid tissue is the principal component of the umbilical
cord, where it is referred to as Wharton’s jelly .
With abundant ground substance composed chiefly of hyaluronan, mucoid tissue is gelatinous, with sparse collagen fibers and scattered fibroblasts. Included among the fibroblastic cells are many mesenchymal stem cells, which are being studied for their potential in regenerative medicine.
