Connective Tissue Proper Lecture Sep 26 Flashcards
What are the three components of connective tissue proper?
cells
fibers
amorphous intercellular substance (ground substance)
What are some of the general characteristics of CT?
- there is abundant matrix (fibers and ground substance)
- the proportions of cell and intercellular substance vary considerably and form a basis of classification
What are the embryological origins of CT?
mesoderm —-> mesenchyme —> CT
What are the three types of fibers in CT?
- Collagenous fibers
- Reticular Fibers (type III collagen)
- Elastic fibers
In regards to collagenous fibers:
Diameter?
What are they comprised off?
What is their shape?
Are they elastic?
What will they form when placed in boiling water?
How do you stain collagenous fibers?
They are 1-2 micrometers in diameter
they are comprised of smaller fibrils
their shape is irregular and undulating
they are inelastic
they form gelatin in boiling water
To stain then, use acid dyes (eosinophilic or acidopilic)
In a little more detail, what are collagenous fibers comprised of?
They are comprised of smaller fibrils which are about .2 to .5 micrometers in diameter.
THese fibrils are held togehter by an amorphous material which is trypsin sensitive
They are aligned in parallel
How is collagen part of the basis of tanning process in the preparation of leather?
Collagen + heavy metals (or tannic acid) yields an insoluble product
What will a collagenous fiber look like under an electron microscope?
the fibrils can be resolved into microfils, which reveals a characteristic cross banding of about 640 nm plus characteristic intraband patterns
What is the chemical composition of collagenous fibers?
Collagen fibers are made from the macromolecule tropocollagen
Tropocollagen consists of three chains of polypeptides called alpha chains
the amino acids of the alpha chains will vary to produce different types of collagen
The alpha chains wrap around each other to form a triple helix held together by hydrogen bonds
The tropocollagen molecules are then polymerized into fibrils in the fibroblasts
THe fibrils then aggregate to form a collagen fiber
What accounts for the 640 nm spacing in collagen observed under electron microscopy?
the regular, staggered arrangement of tropocollagen molecules
Where are the 5 collages types located?
1: ordinary connective tissues (loose and dense) and bone
2: hyaline cartiage
3; loose CT, blood vessel walls; dermis; placenta
4: basement membranes
5: widespread
Where are collagent fibrils and fibers assembled?
in fibroblasts
What are reticular fibers made of?
type 3 collagen
Describe reticular fibers:
relative size?
how do they stain?
what do they form?
How are they different from other collagens?
They are relatively small
they tend to branch into fine networks
they stain with silver stains and PAS
they differ from other collagens in that they have more carbohydrates
How do reticular fibers look under electron microscopy?
THey are morphologically similar to collagen but have a smaller diameter
they exhibit 64 nm cross-banding
WHere are reticular fibers located?
Reticular fibers are sparse in adult loose CT
they are around muscle cells, nerves, and epithelial structures
they are around glandular organs
lymphatic tissues/organs but NOT the thymus
red bone marrow (hemopoietic tissue)
emryonic CT
Where do reticular fibers originate?
fibroblasts
reticular cells in lymphatic and hemopoietic tissues
Describe elastic fibers:
relative size?
what do they form?
what color are they in high concentrations
where are they fenestrated?
What will stain them?
THey are thinner than collagenous fibers
they may reach 10-12 mm in elastic ligaments
they branch and anastomose freely
they are highly refractile
they may be yellowish in high concentrations
they may be fenestreated in the arterial walls
they stain with orcein, resorcin-fuchsin, and aldehyde-fuchsin
What are the 4 most common amino acids in the alpha chains of tropocollagen?
glycine
proline
hydrosyproline
hydroxylysine
What is the most prevalent form of collagen?
type 1
which collagen type is prevalent in loose connective tissue?
type 3
where is type 2 cartilage located?
hyaline carilage
what collagen type is prevalent in the basement membranes
type 4
What do you need to stain reticular fibers? why does this work?
you can use silver stains and PAS
PAS will work because reticulr fibers are much more glycosylated than other collagens
What form of connective fibers are particularly common in the lymphatic system (just not the thymus)?
reticular fibers = type 3 collagen
Will you see elastic fibers on an H&E stain?
no.
you need something special: orcein, resorcin-fuchsin, aldehyde fuchsin
What are the two distinct components of elastic fibers?
fibrillin (the microfibrils)
elastin (in the amorphous component)
Will reticular fibers exhibit cross banding under microscopy?
Will elastic fibers?
reticular fibers will (remember, it’s collagen which is made from tropocollagen which causes the banding udner stain)
elastic fibers will not
What is the important capability of elastic fibers that collagen does not have?
elastic fibers can stretch to about 150% of the original length
What two amino acids are associated with elastic fibers that are not in collagen?
What do they do for the elastic fibers?
Desmosine and Isodesmosine
They are important in the extracellular polymerization of elastin and allow the fibers to stretch
What results from a gene defect in fibrillin?
Marfan’s syndrome - they think Abe Lincoln had this
they are usualy tall with long hands and feet.
They dont make fibrillin, which is important for the integrity of elastin fibers and sheets. They are particularly susceptible to aortic dissection
What fiber is damaged by prolonged sun exposure, leading to photoaged skin?
it results in extensive remodeling of fibrillin midrofibrils - they lose their elasticity
What are the origins of elastic fibers?
fibroblasts
AND
smooth muscle cells if there aren’t fibroblasts around
What are the 4 main chemical components of the amorphoud intercellular substance (ground substance)
- bound water
- glycosaminoglycans
- proteoglycans (and aggregates of)
- Structural multi-adhesive glycoproteins
The glycosaminoglycans in the gound substance come in two basic flavors which are?
non-sulfated and sulfated
what is the most important non-sulfated glycosaminoglycan in the ground substance?
hyaluronic acid
it’s very viscous in solution
it’s made of alternating glucosamine and glycouranate
they account for the physical characteristics of the ground substance: barrier to bacteria and present in synovial joints because they have good lubricating properties
what’s the basic structure of a glycosaminoglycan?
it’s a long molecule of repeating disaccharide units. Some will be sulfated others won’t.
WHat is the basic structure of a proteoglycan?
a protein backbone with sugars (most often these sugars as the sulfated glycosaminoglycans)
What do proteoglycan aggregates attach to?
hyaluronic acid
(told you it was important)
What proteoglycan is prevalent in the lamina densa? What is it’s associated sulfated glycosaminoglycan?
What proteoglycan is associated with cartilage? What are its associated sulfated glycosminoglycans?
Perlecan is prevalent in the lamina densa, with its heparin sulfate.
Aggrecan is common in cartilage with chondroitin sulfate and keratan sulfate
What are the two main types of structural multi-adhesive glycoproteins located in the ground substance?
Which one is the most abundant in connective tissue?
Fibronectin
Laminin
fibronectin is the most abundant
Describe fibronectin
what is it made of?
what does it do?
Fibronectin is made of 2 monomers connected by disfulde bonds
it is located in the mesenchymal tissues, extracellular spaces, and basement membranes
their runction is to organize extracellular matrix by binding to many different macromolecular species (which it can do because it has multiple binding sites)
Describe the structural glycoprotein laminin.
It’s only in the basement membranes
it has structural and ahesive functions
It forms meshwork polymers and binds many diferent things through its multiple cell surface receptors: type 4 collagen, perlecan, and entactin
What are the 3 general functions of the ground substance?
- Efficiency space filler
- Permits passage of gases, ions and small particles
- immobilizes larger objects like bacteria (that’s why bacreria like to have hyaluronidase)
What is the origin of all the gound substance materials (except laminin)?
fibroblasts
What are the 7 groups of connective tissue cells (NOT fibers and NOT ground substance)?
- Fibroblast
- Mesenchymal cells and pericytes
- Macrophages
- Plasma cells
- Mast cells
- Fat cells
- Visitors from the blood (monocytes, lymphocytes, eosinophiles, neutrophils)
Which is the most common CT cell?
fibroblasts
What will an active fibroblast look like?
large, ovoid with branching, sharp processes
oval nuclei
distinct nucleolus
basophilic cytoplasm (will stain because there’s a lot of RER and ribosomes which have a bunch of negatively charged phosphate groups)
enlarged golgi
numerous cytoplasmic vesicles
How will inactive fibroblasts look different from active fibroblasts?
- smaller nucleus
- less distinct nucleoli
- cytoplasm will be slightly acidophili, not basophilic
- reduced RER and ribosomes
- small golgi
- only a few cytoplasmic vesicles
What is the function of fibroblasts?
they produce the CT fibers
they produce the ground substance (except laminin)
What is scurvy’s affect on connective tissue?
It’s a deficiency in Vit C, which is required for the ocnversion of proline to hydroxyproline and lysine to hydroxylysine in the alpha chains of the tropocollagen.
this means the collagen breaks down and you get a generalized degeneration of CT
Describe Ehlers-Danlos syndrom
there are 7 variants involving malfunctional connective tissue (for example, one version is the extension regions of tropocollagen not be removed)
people are usually short with stretchable skin and hypermobility of joints/joint dislocation
what happens in osteogenesis imperfecta?
there isn’t sufficient collagen made to support the skeleton, resulting in brittle bone disease
What is the precursor for basically all the connective tissue cells including fibroblasts, smooth muscle prescursor, etc?
The mesenchymal cells
and pericytes
Describe the appearance of macrophages
they are irregularly shaped cells with blunt processes (so they look smoother than the sharper fibroblasts)
they have a round small, dark-staining nucleus
the cytoplasm stains lightly and may contain granules and vesicles
*active macrophages will be larger and will have many granuoles and vacuoles in the cytoplasm
What are the functions of macrophages?
They are mainly for phagocytosis of things the body doesn’t want, like dead cells or bacteria.
they are able to do this by using ameboid movement to escape the capillaries and inter the CT to reach the site of infection
THey can then multiply in the area where they’re needed.
WHat will macrphages do if the foriegn body is too big to phagocytose?
they will join together to make multinucleated giants cells
How do macrophages allert the T and B cells of invasion?
They take antigen from whatever they phagocytosed and present it on proteins on their membrane
What receptors do macrophages have on their membranes to aid in phagocytosis?
Fc receptors (will bind to the long end of IgE that have bound their antigen targets)
C3 receptors (will bind to complement that has opsonized the target)
WHat are plasma cells?
Where are they in the body?
What do they do?
Plasma cells are differentiated B cells that produce antibodies inr esponse to infection
they are prevalent in the lamina propria of digestive tract, omentum, and reticular connective tissue of blood forming organs
their numbers will increase in areas of chronic inflammation
What do plasma cells look like under microscopy?
THey are egg shaped
the spherical nucleus is located towards one side of the egg
the chromatin sometimes has a wagon wheel appearance
the cytoplasm is very basophilic (because there’s extensive RER), but there will be a clear area just adjacent to the nucleus hwere the golgi is.
A tumor of plasma cells is called what?
multiple myeloma
What will mast cells look like under microscopy?
large, ovoid cells
small nucleus
the cytolasm will have MANY granules
the cytoplasm will be basophilic, but if you stain it with somehting blue, the cytoplasm will actually stain red because of the metochromatic shift
WHat do the membrane-bound granules of mast cells contain?
histamine
heparin (important maingly because it allows the cells to be stained)
What are the effects of histamine release?
vasodilation (dilates blood capillaries increasing their permeability)
bronchoconstriction
What is the mast cell role in anaphylaxis?
Someone was exposed to something and the body inappropriately made lots of IgE to the antigen
the IgE bound to receptors on the surface of mast cells
If the person is exposed to the antigen a second time, the antigen will bind to the IgE
If the bound IgE touch each other on the mast cell surface, this triggers the mast cell to degranulate and release histamine
the histamine causes vasodilation and bronchioconstriction = respiratory and circulatory failure
WHat do fat cells look like under microscopy?
signet ring shape
nucleus forms a slight bulge at cell surface
large central lipid droplet
thin rim of cytoplasm around lipid droplet
each cell is surrounded by a network of reticular fibers
some golgi, mitochondria
no membrane around lipid droplet
Will mature fat cells divide?
They will only divide if they reach 4x their original size
anything less than that and they’ll just wax and wane
What are the 3 functions of fat cells?
- storage of fats or triglycerides
- carb and fat metabolism
- endocrine functions (letin and adiponectin)
What are the 4 main “visitors from the blood” in the CT?
monocytes (become macrophages)
lymphocytes (t cells and b cells - become plasma cells)
eosinophils
neutrophils
WHat are monocytes?
They are the blood cells that migrate from the blood stream into connective tissue spaces near sites of inflammation and become macrophages
WHat does a lymphocyte look like under microscopy?
they are small and round with dark staining nucleus that fills most of the cell. only a htin rim of cytoplasm
What are the 3 kinds of lymphocytes?
T cells (cell-mediated immune response)
B cells (initiates the humoral immune response)
NK cells (cytotoxic killing mechanisms)
What do eosinophils look like under microscopy?
THey are large, with bi-lobed nuclei.
They have numerous, alrge eosinophilic granules which are frequently crystalline inside
What to eosinophils respond to?
parasitic infections
but they’re also involved in allergic hypersensitivities lik asthma.
What do neutrophils look like?
they have a multi-lobed nucleus
granular cytoplasm
What is the function of a neutrophil?
They are the first line of cellular defense against invasion by microorganisms
they are phagocytic cells
they form pus cells when they die.
What do all mononuclear phagocyte cells have in common?
all come from the same stem cell in the bone marrow
all have Fc and C3 receptors
They are all macrophages capable of phagocytosis
Many (if not all) are capable of antigen presentation
Include: macrophages, kupffer cells, microglia, dust cels, osteoclasts, and langerhans cells
What will embryonic connective tissue include? (2)
- Mesenchyme
- Mucous CT
What are the 4 varieties of adult connective tissue?
loose CT (areolar)
Dense CT (includes irregular and regular)
Adipose CT
Reticular CT
What are some characteristics of loose connective tissue?
- its irregularly arranged
- appears cobwebby with loosely arranged interlacing fibers
- “spaces” (aerolae) are due to gound substance
What are the continuents of loose CT?
Cells: fibroblast and macrphages are most common, but all other CT cells are present to some extent
FIbers: MOSTLY collagenous, but elastic and reticular are present to a lesser extent
ground substance
What are the characteristics of Dense Irregular CT?
THe constitutent fibers are irregularly arranged
What are the components of dense irregular CT
Fibers: coarse collagenous fibers predominate, elastic and reticular are present to a lesser extent
Cells: fibroblasts and macrophages are the most common
ground substance
The difference between loose and dense is that the collagen fibers are much more prevalent and orderly in dense
What are the two forms of dense regular CT?
- predominantly collagenous
- predominately elastic
What are some characteristics of dense regular CT?
- the collagenous or elastic fibers are lined up IN PARALLEL
- Well-sited for withstanding tension in one direction (as in tendons and ligaments)
- Fibroblast is the major cell between the fibers
Where are dense regular collagenous CT located?
WHere is dense regulst elastic CT located?
collagenous: ligaments, tendons, aponeuroses
elastic: ligamenta flava, vocal cords, susepsnroy ligament of penis
What are some characteristics of adipose tissue?
- adipose tissue is numerous fat cells arranged in groups or lobules
- the adipose cells are surrounded by an external lamina and fine colagenous, reticular and elastic fibers
What is reticular connective tissue
This is really just a concept until you use a reticular stain
it provides a find fibrillar network in lymphoid tissues and bone marrow
What are the 4 causes of edema?
Increased formation of tissue fluid:
1 hydrostatic pressure impeding venous return, fluid leaves capillaries
- Increased capillary permeability: fluid leaves in response to heat, cold, and histamine
Decreased Reabsorption of Tissue Fluid:
- Decreased blood colloid from starvation, renal disease, or burns (no osmotic drive to bring fluid back into capillaries)
- Decreased lymphatic draimage as in cancer and elephantiasis
