Connective Tissue

Compiled by Dr. Girmay ( Assistant professor)

 General Properties of Connective Tissue
• formed primarily of extracellular matrix (ECM) , consisting of ground
substance and fibers, in which various connective tissue cells are embedded
• provide a matrix that supports and physically connects other tissues and cells
together in organs
• The interstitial fluid of connective tissue gives metabolic support to cells
as the medium for diffusion of nutrients and waste products
• Unlike the other tissue types which consist mainly of cells, the major
constituent of connective tissue is the extracellular matrix (ECM)
• Does not occur on free surfaces
• Has a nerve supply (except cartilage)
• Highly Vascular (except cartilage and tendons)
 Connective Tissue cont…
• Composition of connective tissue:
• cells (fibroblasts and others),
• Fixed: Fibroblasts, Adipocytes, “Tissue macrophages”
• Free:
• Immune cells (lymphocytes)
• Inflammatory cells (neutrophils & activated macrophages)
• fibers and ground substance (extracellular matrix)
• Fibers – collagen & elastic
• “Ground substance”:- a complex of anionic, hydrophilic
• proteoglycans, glycosaminoglycans (GAGs), and multiadhesive
glycoproteins (laminin, fi bronectin, and others)
• Connective tissue is composed of
fibroblasts and other cells and an
extracellular matrix (ECM) of
various protein fibers, all of
which are surrounded by watery
ground substance

• in all types of connective tissue

the extracellular volume exceeds
that of the cells.
 Connective tissue cont…
• Function.
• Architectural framework of the body
• supports organs and cells,
• acts as a medium for exchange of nutrients and wastes between the
blood and tissues,
• protects against micro organisms,
• repairs damaged tissues, and
• stores fat.
 CELLS OF CONNECTIVE TISSUE
Fixed connective tissue cells
• originate locally and remain in
the connective tissue
• include:
• Fibroblasts
• Pericytes
• adipose cells
• mast cells, and
• fixed macrophages
Transient connective tis­sue cells
• originate elsewhere and remain
only temporarily in connective
tissue) include
• certain macrophages,
• lymphocytes,
• plasma cells
• neutrophils,
• eosinophils, and
• basophils.
 Cells in Connective Tissue

1. Fibroblasts
Fixed
(permanent
2. Pericytes
residents) 3. Adipose (fat) cells
4. Tissue Macrophages**
5. Mast cells**

Free 1. Lymphocytes & Plasma Cells (differentiated B-

(transient cells) **
residents)
2. “Leukocytes”** (specifically, neutrophils,
eosinophils, & basophils)

** derived from hematopoietic stem cells and involved in immune function

and inflammation
 Cells of CT cont….
• Origin of connective tissue cells:
• Cells arising from undifferentiated mesenchymal cells are
formed in con­nective tissue and remain there
• Cells arising from hematopoietic stem cells are formed in
the bone marrow and reside transiently in connective tissue.
Cells arising from
undifferentiated mesenchymal
cells
Cells arising from hematopoietic stem cells
Fixed cells of connective tissue
1. Fibroblasts
• arise from mesenchymal cells
• are the predominant cells in connective tissue proper
• They often possess an oval nucleus with two or more nucleoli
• Fibroblasts seldom undergo mitosis except in wound healing
• They may differentiate into other cell types under certain conditions
•Two levels of fibroblast activity can be observed histologically
• Active and quiescent fibroblasts
• Some histologists reserve the term “fibroblast” to denote the active cell
and “fibrocyte” to denote the quiescent cell.
Cells of connective tissue cont…
Active fibroblasts
• Cells with intense synthetic activity
• has more abundant and irregularly
branched cytoplasm
• Its nucleus is large, ovoid,
euchromatic, and has a prominent
nucleolus
• The cytoplasm has much rough
endoplasmic reticulum (RER) and a
well-developed Golgi apparatus
quiescent fibroblasts
• are scattered within the matrix
they have already synthesized.
• is smaller than the active cells
• is usually spindle-shaped with fewer
processes and much less RER,
• contains a darker, more
heterochromatic nucleus
 Fixed cells of connective tissue cont…
2. Pericytes (adventitial cells; perivascular cells)
• are derived from embryonic mesenchymal cells and may retain a pluripotential
role
• They possess characteristics of endothelial cells as well as smooth muscle
cells because they contain actin, myosin, and tropomyosin, suggesting that they
may function in contraction where they assist to modify blood flow through
capillaries
• They are smaller than fibroblasts
• are located mostly along capillaries
• are completely enveloped by their own basal lamina, which is continuous with
the basal lamina of the capillary endothelium
• During blood vessel formation and repair, they may differentiate into
fibroblasts, smooth muscle cells, as well as endothelial cells of blood vessel
walls
Cells of CT cont…
3. Adipocytes (L. adeps, fat + Gr. kytos, cell), or fat cells,
• are found in connective tissue of many organs
• 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.
• Adipogenesis occurs pre- and postnatally, and its rate is reduced in aging.
• Adipocytes do not normally undergo cell division because they are fully
differentiated cells.
• However, they do increase in number in early neonatal life
• There is debate about normal proliferation of adipocytes beyond 2 years after birth,
although in obese individuals the cells not only become enlarged but also form new
fat cells
 Adipocytes predominate in adipose tissue

Very active cells with many

functions:
• are responsible for the synthesis,
storage, and release of fat. Single, large
• Triglyceride storage and glucose lipid droplet
metabolism (insulin and glucagon
receptors)
• Secretion of many bioactive
molecules:
leptin (regulates satiety) angiotensinogen
(blood pressure) steroids (glucocorticoids
& sex hormones)
growth factors (e.g. insulin-like growth
factor, tumor necrosis factor ) cytokines
(e.g. interleukin-6) White (common, yellow, unilocular) adipose tissue stained with Masson’s trichrome
• There are two types of fat cells,
1. unilocular
2. multilocular.
• Unilocular adipose cells
– contain a single large fat droplet
– To accommodate the large fat droplet, the
Lipid (fat)
cytoplasm and nucleus are squeezed into a droplet
thin rim around the cell's periphery.
– cells have plasmalemma receptors for
insulin, growth hormone, norepinephrine,
and glucocorticoids to control the uptake
and release of free fatty acids and
Nucleus
triglycerides.
– They are surrounded by a basal lamina and
are responsible for the synthesis, storage,
and release of fat. Capillaries
 Brown (Multilocular) Adipose Tissue
Present in newborns (and hibernating mammals) and involved in thermoregulation

• Multilocular adipose cells are

white
smaller than unilocular
adipose cells, and the fat is
stored as many small fat
droplets, and thus the
spherical nucleus is centrally
located
• Mitochondria of brown fat
cells express uncoupling
protein which “short circuits”
the electron transport chain brown
producing HEAT rather than
ATP.
Cells CT cont…
4. 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
– arise from myeloid stem cells in bone marrow
– usually reside near small blood vessels
– Although they share many structural and functional characteristics with basophils, they
develop from different precursors and are not related.
– These cells are one of the largest cells of connective tissue proper.
– They possess a central spherical nucleus;
– These granules are electron-dense and heterogeneous (ranging from 0.3 to 2.0 μm in
diameter.)
– 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 (eg,
toluidine blue) from blue to purple or red.
– The granules are poorly preserved by common fixatives, so that mast cells are frequently
difficult to identify.
 Cells CT cont…
• Mast cells cont…
– Their surf aces are folded, and in electron micrographs they have a well-
developed Golgi complex, scant RER, and many dense lamellated
granules.
– Two populations of mast cells exist.
• Connective tissue mast cells possess secretory granules containing heparin.
• mucosal mast cells
– are smaller than the CT mast cells
– Their secretory granules contain chondroitin sulfate,
– located in the mucosa of the alimentary canal and of the respiratory tract.
– Interestingly, there are no mast cells in the central nervous system
presumably to prevent the possibility of an inflammatory response.
 Mast Cells
• Principal function is storage in secretory
granules and REGULATED release
(degranulation) of histamine and other
vasoactive mediators of inflammation.
• Responsible for the immediate hypersensitivity
response characteristic of allergies, asthma and
anaphylactic shock.
• Connective tissue mast cells are found in skin
(dermis) and peritoneal cavity; mucosal mast
cells are in the mucosa of the digestive and
respiratory tracts.

Metachromasia – when stained with toluidine blue, the granules bind the dye and change its
color to red.
EM of a Mast Cell
• ultrastructurally mast cells show
little else around the nucleus (N)
besides these cytoplasmic
granules (G), except for occasional
mitochondria (M).
• The granule staining in the TEM is
heterogeneous and variable in mast
cells from different tissues; at
higher magnifications some
granules may show a characteristic
scroll-like substructure (inset) that
contains preformed mediators such
as histamine and proteoglycans
• The ECM near this mast cell
includes elastic fibers (E) and
bundles of collagen fibers (C).
 Cells CT cont…
• Mast cells function in the localized release of many bioactive substances with roles in
the local inflammatory response, innate immunity, and tissue repair.
• A partial list of important molecules released from these cells’ secretory
granules includes the following:
– 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 Cell Secretion
• Mast cell secretion is triggered by
reexposure to certain antigens and
allergens.
• Molecules of IgE antibody produced in
an initial response to an allergen such as
pollen or bee venom are bound to surface
receptors for IgE(1), of which 300,000
are present per mast cell.
• When a second exposure to the allergen
occurs, IgE molecules bind this antigen
and a few IgE receptors very rapidly
become cross-linked (2).
• This activates adenylate cyclase, leading
to phosphorylation of specific proteins
(3), entry of Ca2+ and rapid exocytosis
of some granules (4).
• in addition, phospholipases act on specific membrane phospholipids, leading to production and release of leukotrienes (5).
• The components released from granules, as well as the leukotrienes, are immediately active in the local microenvironment
and promote a variety of controlled local reactions that together normally comprise part of the inflammatory process called
the immediate hypersensitivity reaction. “ECF-A” is the eosinophil chemotactic factor of anaphylaxis.
FIGURE Activation and
degranulation of the mast cell.
ECF, eosinophil chemotactic factor;
NCF, neutrophil chemotactic factor
Major Mediators Released by Mast Cells
 Transient cells of connective tissue
1. Macrophages
– are the principal phagocytosing cells of connective tissue
– They are responsible for removing large particulate matter and assisting in the immune
response.
– They also secrete substances that function in wound healing.
– Macro phages originate in the bone marrow as monocytes, circulate in the bloodstream, and
then migrate into the connective tissue, where they mature into functional macro phages
– The transformation from monocytes to macrophages in connective tissue involves increases
in cell size, increased protein synthesis, and increases in the number of Golgi complexes
and
– lysosomes.
– Macrophages increase in number because of the activity of the macrophage colony-
stimulating factor (M- CSF). In addition, the colony-forming unit monocyte (CFU-M)
facilitates the mitosis and differentiation of monocytes to form macrophages.
 Transient cells of connective tissue cont..
• Macrophages & the Mononuclear Phagocyte System
– Macrophages are characterized by their well-developed phagocytic ability and
specialize in turnover of protein fibers and removal of dead cells, tissue debris, or
other particulate material
– They have a wide spectrum of morphologic features corresponding to their state of
functional activity and to the tissue they inhabit
– A typical macrophage measures between 10 and 30 μm in diameter and has an
eccentrically located, oval or kidney-shaped nucleus
– Macrophages are present in the connective tissue of most organs and are often
referred to by pathologists as “histiocytes.”
– Along with other monocyte-derived cells, they comprise a family of cells called
the mononuclear phagocyte system
Cont…
– Macrophages are members of the mononuclear phagocyte system.
– They are anti gen presenting cells, in that they phagocytose antigens, break them
down into epitopes, and, using MHC I or MHC II molecules, place the epitopes on
their cell surface to present it to immunocompetent T cells (see Chapter 12
Section III) . For historical reasons, macrophages have different names in various
regions of the body (e.g., Kupffer cells in the liver , dust cells in the lungs,
osteoclasts in bone, Langerhans cells in skin, microglia in the central nervous system).
Macro phages display Fc£RI receptors as well as receptors for complement.
– When activated, they display filopodia, an eccentric kidney- shaped nucleus,
phagocytic vacuoles, lysosomes, and residual bodies.
– When stimulated, they may fuse to form foreign body giant cells. These
multinucleated cells surround and phagocytose large foreign bodies.
Monocytes escape from blood vessels into connective tissue where they
differentiate into Macrophages

Primary function: phagocytosis and antigen presentation

Ultrastructural features of a Macrophage
secondary lysosomes

phagocytic vesicles

Junqueira and Carneiro. Basic Histology. Tenth Edition. 2003. Figure 5.7.
 Transient cells of connective tissue cont..
2. Lymphoid cells:
•arise from lymphoid stem cells during hemopoiesis
•They are located throughout the body in the sub-epithelial connective tissue
and accumulate in the respiratory system, gastrointestinal tract, and
elsewhere in areas of chronic inflammation
a) T lymphocytes (T cells) initiate the cell-mediated immune response .
b) B lymphocytes (B cells), following activation by an antigen, differentiate into plasma
cells, which function in the humoral immune response
c) Natura l killer (NK) cells lack the surface determinants characteristic of T and B
lympho­cytes but may display cytotoxic activity against tum or cells
 Transient cells of connective tissue cont…
3. Plasma cells
• are antibody-manufacturing cells that arise from activated B
lymphocytes and are responsible for humoral immunity.
• These ovoid cells contain an eccentric nucleus possessing clumps of
heterochromatin, which appear to be arranged in a wheel-spoke fashion
• Many of these nuclei contain compact, peripheral regions of heterochromatin
alternating with lighter areas of euchromatin, a configuration that can give the nucleus
of a plasma cell the appearance of a clock face
• There are at least a few plasma cells in most connective tissues
• Their average lifespan is only 10-20 day
• Their cytoplasm is deeply basophilic because of an abundance of RER.
• A prominent area adjacent to the nucleus appears pale and contains the Golgi
complex (negative Golgi image)
• They are most abundant at wound entry sites or in areas of chronic inflammation
MEDICAL APPLICATION
• Plasma cells are derived from B lymphocytes and are responsible for the
synthesis of immunoglobulin antibodies. each antibody is specific for the
one antigen that stimulated the clone of B cells and reacts only with that
antigen or molecules resembling it
• The results of the antibody-antigen reaction are variable, but they usually
neutralize harmful effects caused by antigens. an antigen that is a toxin
(e.g., tetanus, diphtheria) may lose its capacity to do harm when it binds to
its specific antibody.
• bound antigen-antibody complexes are quickly removed from tissues by
phagocytosis.
 Transient cells of connective tissue cont…
4. Granulocytes
• are white blood cells that possess cytoplasmic granules and arise
from myeloid stem cells during hemopoiesis.
• They leave blood by migrating between the endothelial cells lining
venules to enter connective tissue by a process called diapedesis
• This process increases greatly during inflammation, which is a vascular
and cellular defensive response to injury or foreign substances, including
pathogenic bacteria or irritating chemical substances
• At sites of inflammation, they leave the bloodstream and enter the
loose connective tissue, where they perform their specific functions
a)Neutrophils phagocytose, kill , and digest bacteria at sites of acute
inflammation. Pus is an accumulation of dead neutrophils, bacteria,
extracellular fluid, and additional debris at an inflammatory site.
Transient cells of connective tissue cont…
Granulocytes cont…
a)Eosinophils
1) bind to antigen- antibody complexes on the surface of parasites (e.g., helminthes) and then release
cytotoxins that damage the parasite s.
2) They are most prevalent at site s of chronic or allergic inflammation
3) Eosinophils are attracted by eosinophil chemotactic factor (ECF), which is secreted by mast cells and
basophils, to sites of allergic inflammation. There, eosinophils release enzymes that cleave
histamine and leukotriene C, thus moderating the allergic reaction.
4) These cells also phagocytose antibody-antigen complexes.
b)Basophils
• are similar to mast cells in that they possess FCERI receptors;
• their granules house the same primary mediators; and the same secondary mediators are manufactured
de novo from the phospholipids of their plasmalemma.
• They differ, however, in that they circulate via the blood stream, whereas mast cells do not.
 Extracellular matrix
• The ECM provides a medium for the transfer of nutrients and waste
materials between connective tissue cells and the blood stream.
• ECM: ground substance and fibers
• Ground substance
• is a colorless, transparent, gel- like material in which the cells and fibers of
connective tissue are embedded.
• It is a complex mixture of glycosaminoglycans, proteoglycans, and
glycoproteins
• It serves as a lubricant, helps to prevent invasion of tissues by foreign agents,
and resists forces of compression
Fibers in Connective Tissue
• The fibrous components of connective tissue are elongated structures formed from
proteins that polymerize after secretion from fibroblasts
• The three main types of fibers are:
• Collagen
– most abundant protein in human body (up to 30% dry weight)
– multiple types: fibril-forming or fibril-associated (in skin, tendon, cartilage, bone,
dentin, blood vessels); cross-linked networks (in all basement membranes)
• Reticular Fibers – specialized type of collagen (Type III; reticulin) associated with
smooth muscle in organs subjected to changes in volume, forms the stroma in lymphatic
and hematopoietic organs
• Elastic Fibers –thin fibers or fenestrated sheets composed of various glycoproteins,
including the protein elastin, providing elastic properties to tissues that experience
repeated deformation (in skin, blood vessels, lung, bladder)
 Collagen
• Is key element of all CT, epithelial basement membrane and the external
lamina of muscles and nerve cells
• The most abundant protein in the human body, representing 30% of its dry
weight
• A family of 28 collagen exist in vertebrae
• Can be grouped into the following according to the structures formed by their
interacting subunits:
– Fibril forming collagen
– Sheet forming collagen
– Linking/ anchoring collagen
 Major Collagen Fiber Types (out of at least 20)

Collagen Type Tissues Function

Fibril-forming collagens (these are visible)
I
Skin, tendon, bone, dentin Resistance to tension
(most abundant)
II Cartilage, vitreous of eye Resistance to pressure
III Skin, muscle, blood vessels, liver,
Structural framework and stability
(reticulin) etc.
Network-forming collagens
IV All basement membranes Support and filtration
Fibril-associated collagens with interrupted triple helices (FACIT)
VI, IX Assoc. w/ type I and II fibrils Fibril-fibril / fibril-ECM binding
Anchoring filament collagens

VII Epithelia Epidermis to basal lamina

Collagen types
Collagen types cont…
Collagen fibers viewed by light microscopy
H&E Trichrome

University of Michigan Histology Collection University of Michigan Histology Collection

 Collagen fibers
viewed by TEM*

Longitudinal

Source Undetermined

Transverse

*TEM, transmission Source Undetermined

electron microscopy
 Collagen Fibrils (Type I)

Ross,M, Pawlina, W. Wheater’s Functional Histology: A Text and Atlas. Fifth Edition. 2006. Figure 4.2.
 Collagen Fibers vs. Fibrils
H&E fibrils

fibers

Source Undetermined Junquiera and Carneiro. Basic Histology. Tenth

Edition. 2003.
 Reticular (Reticulin) Fibers
• Form a delicate supporting
framework for highly cellular
tissues (endocrine glands, lymph
nodes, liver, bone marrow,
spleen, smooth muscle).
• Composed mainly of Type III
collagen, with a carbohydrate
moiety that reduces Ag+ to
metallic sliver = argyrophilic.
• Special stain: silver impregnation
to visualize.
• Thinner than type I collagen
(Type III fibrils are 30-40 nm diameter;
type I fibrils are ~200 nm diameter)
University of Michigan Histology Collection
 Reticular Fibers (type III collagen)
• made by reticular cells (specialized fibroblasts) and vascular smooth muscle cells

Top left: Ross,M, Pawlina, W. Wheater’s Functional Histology: A Text and Atlas. Fifth Edition. 2006.
Figure 6.12.
Bottom left and Far right: Source Undetermined
 Clinical disorders resulting from
defects in collagen synthesis

Type Disease Symptoms

I Osteogenesis Spontaneous fractures, progressive
imperfecta hearing loss, cardiac insufficiency
III Ehlers-Danlos Hypermobility of digits, early
(type IV) morbidity/mortality from rupture of
aorta or intestine
multiple Scurvy (lack of vit. C, Ulceration of gums, hemorrhages
a cofactor for prolyl
and lysyl hydroxylase)
Source Undetermined
 Ehlers-Danlos Syndromes

• A series of genetic diseases

with faulty assembly of
collagens (lysyl hydroxylase
deficiency).
• Hyperextensible skin and
hypermobile joints
• In some forms (e.g., type IV),
weakness in blood vessels or
intestines are life threatening.

Source Undetermined
 Non-collagen Components of
the Extracellular Matrix

• Elastin
• “Ground substance”
– Glycosaminoglycans (GAG’s)
– Proteoglycans
– Multiadhesive matrix proteins
• laminin
• fibronectin
 Elastic Fibers
LM: Visualized by selectively staining with Weigert’s, resorcin-fuchsin, or aldehyde-fuchsin

EM: Consist of amorphous core of elastin surrounded by microfibrillar glycoprotein, fibrillin (8-
10nm).

Elastin: is rich in glycine and proline, but it contains little or no hydroxyproline and hydroxylysine .
uniquely contains desmosine and isodesmosine, which are thought to cross-link the
molecules into a network of randomly coiled chains. This cross-linking is responsible for its
rubber-like properties.

Confers elasticity: present in large amounts in ligaments, lung, skin, bladder, and walls of
blood vessels.

Marfan Syndrome: defect in elastic fiber synthesis; reduced elasticity in skin and lungs, skeletal
defects (bones are longer and thinner than usual), cardiovascular complications (aneurism,
valve prolapse)
Network of elastin molecules can stretch and
recoil like a rubber band

Alberts et. al. Molecular Biology of the Cell.

 Elastin appears amorphous (not
fibrillar) in the electron microscope

Source Undetermined

Ross,M, Pawlina, W. Wheater’s Functional Histology:

Image of elastin
A Text and Atlas. Fifth Edition. 2006. Figure 4.4. removed
E=elastin C, collagen fibrils
M/L=microfibrils of fibrillin, a scaffolding
glycoprotein involved elastin deposition
Marfan Syndrome: defect in fibrillin gene, results in
weakened elastic fibers
 Elastic and Collagen Fibers

University of Michigan Histology Collection University of Michigan Histology Collection

elastin stain (“Weigert’s”, “aldehyde fuchsin”, “Verhoeff”):

H&E stain: collagen stains orange/pink; elastic fibers stain elastic fibers are purple/black
glassy red (generally only visible if in HIGH abundance) collagen fibers stain orange/pink or blue/green depending on
other stains used (von Gieson’s or trichrome, respectively)
Ground Substance of the Extracellular Matrix (ECM)
1. Glycosaminoglycans (GAG)
• linear (unbranched) polysaccharides, e.g. heparan sulfate, condroitin sulfate, keratan sulfate,
hyaluronic acid
• very hydrophilic due to abundant negative charges (e.g. SO 4- groups).
• except for hyaluronic acid, are usually bound covalently to protein core as part of a
proteoglycan

2. Proteoglycans
• core protein + GAG side chains (like a bottle brush)
• bind cells, other proteins, and/or ECM components

3. Multiadhesive glycoproteins
• small glycosylated proteins containing NUMEROUS binding sites to cells, signaling molecules,
and other ECM components
• e.g. fibronectin and laminin: important for adhesion of epithelial cells to the basal lamina via
transmembrane integrin receptors.
 Ground
Substance

Junquiera and Carneiro. Basic Histology. Tenth Edition. 2003. Figure 5-30.
 Basement Membrane –
Collagen Types IV, VII, and III
• Basement membranes are sheets of extracellular matrix proteins
located at the interface of parenchyma (epithelia, endothelia,
muscle, nerves, adipocytes) and connective tissue / ECM.
• Main constituents are glycosaminoglycans (heparan sulfate),
fibrous proteins (collagen types IV, VII, III), structural
glycoproteins fibronectin, laminin and entactin.
• This is NOT a plasma membrane.
Basement membranes vary in thickness
Thick Thin -- requires special stain to visualize

BM

BM
BM
University of Michigan Ross,M, Pawlina, W. Wheater’s Functional Histology:
Histology Collection A Text and Atlas. Fifth Edition. 2006. Figure 4.4.

Intestinal glands, PAS

trachea, H&E PAS reacts with carbohydrate-rich molecules such as perlecan, laminin
and type III collagen associated with the basement membrane.
 Basement Membrane(LM): Three layers in the EM

hemidesmosomes

basal lamina
1. lamina lucida
(LL) or rara 10-50
nm
2. lamina densa
(LD) 20-300 nm
(type IV collagen)

fibroreticular lamina
3. Fibroreticular
FL LL LD lamina (FL)
merges with
underlying CT
(type III* and type VII
collagen fibrils)
Connective tissue
*basement membranes can also
Source Undetermined be visualized with silver stain

So, the “basement membrane” is the basal lamina + the fibroreticular lamina
 Tying it all together
Interactions of many proteins tether
cell to the underlying connective
Image of cell
junctions removed
tissue:
Cell to basal lamina…
• Hemidesmosome
• Type IV collagen
• Integrin/laminin
lamina
rara
Basal lamina to underlying
lamina
densa connective tissue:
anchoring fibril • Type IV collagen
(collagen VII)
• Type VIII collagen
reticular fibril • Fibrillin
(collagen III)
• Type III collagen
Source Undetermined
Types of Connective Tissue

• There are 6 types of connective tissue that vary by the fibers,

ground substance and cells contained in it.
• Each type has a very specific structure and function.
 Loose Connective Tissue
• Fibers are loosely intertwined among many cells.
• 3 types of loose connective tissue
– Areolar Connective Tissue – one of the most widely distributed
connective tissues in the body.
• Contains fibroblasts, macrophages, plasma cells, mast cells,
adipocytes and a few white blood cells as well as all 3 types of fibers
• Helps to form the subcutaneous layer
Loose Connective Tissue
– Adipose Tissue – The cells, called adipocytes, are specialized
for storage of triglycerides. Adipocytes fill up with a large fat
droplet so the nucleus gets pushed to one side of the cell.
• Used for insulation, protection and as an energy reserve
– Reticular Connective Tissue – made of interlacing reticular
fibers and reticular cells that connect to each other to form a
network.
• Used to bind together smooth muscle cells and to filter out worn out
blood cells and bacteria
 Dense Connective Tissue
• Contains more numerous, thicker and denser fibers but
fewer cells than loose connective tissue.
• 3 types:
– Dense regular connective tissue
– Dense Irregular connective tissue
– Elastic Connective Tissue
 Dense Regular Connective Tissue
• Bundles of collagen fibers are arranged regularly in parallel
patterns that give it strength.
• Withstands pulling from the ends, but unravels when pulled from
the side
• Silvery white in appearance. Tough and pliable
• Found in tendons and ligaments
Dense Irregular Connective Tissue
• Collagen fibers are packed closely together in an irregular,
random pattern
• Found in parts of the body where pulling forces are exerted in
various directions
• Usually found in sheets
• Examples: Dermis of the skin, heart valves, perichondrium and
periosteum
 Elastic Connective Tissue
• Contains branching elastic fibers and fibroblasts
• Yellowish in color
• Strong, can regain shape after stretching
• Found in lungs and arteries
 Cartilage
• Dense network of collagen fibers and elastic fibers embedded in
chondroitin sulfate (a rubbery component of the ground substance)
• Can withstand more stress than the dense and loose connective
tissue.
• Collagen fibers make the tissue strong, chondroitin sulfate makes
it resilient
 Cartilage - continued
• Chondrocytes – mature cartilage cells
• Lacunae – holes in the matrix in which the cells sit
• Perichondrium – dense irregular connective tissue that surrounds
cartilage
• 3 types – hyaline, fibrocartilage and elastic
• Cartilage is AVASCULAR and NO nerve supply (but the
perichondrium does)
 Hyaline Cartilage
• Gel like ground substance, collagen fibers (not visible with
normal stains) and prominent chondrocytes
• Most abundant cartilage in the body
• Found at the end of long bones to cushion joints and at
epiphyseal plates (growth plates in bones)
• Weakest of the 3 types of cartilage
 Fibrocartilage
• Chondrocytes scattered among visible bundles of collagen
fibers
• No perichondrium
• Strongest of the 3 types of cartilage
• Found in the intervertebral discs
 Elastic Cartilage

• Chondrocytes located in a threadlike network of elastic

fibers
• Provides strength, elasticity and maintains the shape of
certain structures (like the external ear)
 Bone Tissue (osseous tissue)
• 2 types – compact and spongy
– Compact
• Osteon – basic unit of compact bone
• Lamellae – concentric circles of matrix
• Lacunae – spaces in the matrix that house cells
• Osteocytes – mature bone cells
– Spongy
• Trabeculae – columns of bone with spaces filled with red bone
marrow
Micrograph of Spongy Bone
An electron micrograph scan of spongy bone
in an osteoporosis patient. Osteoporosis
occurs when a body's blood calcium level is
low and calcium from bones is dissolved into
the blood to maintain a proper balance.
 Blood Tissue
• Connective Tissue with a liquid matrix
• Red Blood Cells (erythrocytes) – transport oxygen
• White Blood Cells – function in immunity
– Neutrophils, Eosinophils, Basophils, T and B leukocytes, natural
killer cells and Monocytes
• Platelets – participate in blood clotting
 MCQ
• Plasma Cells are derived from
• 1. Monocytes
• 2. Basophils
• 3.T lymphocytes
• 4. B Lymphocytes
 MCQ
• Large number of elastic fibres are present in
• 1. Tendon
• 2. Ligamentum Nuchae
• 3. Basement Membrane
• 4. Aponeurosis
 MCQ
The fat cells of Multilocular adipose tissue
(Brown fat) is characterized by the presence
of
1.Spherical central nucleus and many lipid
droplets.
2.Flat peripheral nucleus and single lipid
drop
3.Flat central nucleus and single lipid droplet
4.Thin rim of cytoplasm
 MCQ
• Which of the following is NOT TRUE about Collagen
• 1.Constitutes 30% of the dry body weight
• 2.Is synthesized by fibroblasts
• 3.Is composed of Mucopolysaccharides
• 4.Gives gelatin on denaturation