2. CONNECTIVE TISSUES: FunctionsCONNECTIVE TISSUES: Functions
Structural functionStructural function: provide and maintain: provide and maintain FORMFORM inin
the body.the body.
Mechanical functionMechanical function: provide a matrix that: provide a matrix that
CONNECTSCONNECTS andand BINDSBINDS the cells and organs andthe cells and organs and
ultimately gives support to the body.ultimately gives support to the body.
3. Metabolic functionMetabolic function: Provide metabolic support for: Provide metabolic support for
other tissues and organs of the body.other tissues and organs of the body.
Mediate theMediate the EXCHANGEEXCHANGE of nutrients,of nutrients,
metabolites and waste products between tissuesmetabolites and waste products between tissues
and circulatory system.and circulatory system.
Defense functionDefense function:: serves as the arena and providesserves as the arena and provides
the cells that are needed to defend the bodythe cells that are needed to defend the body
against invading organisms and other harmfulagainst invading organisms and other harmful
substances.substances.
4. CONNECTIVE TISSUES: ComponentsCONNECTIVE TISSUES: Components
Structural components:Structural components:
CELLSCELLS – character cells / special support cells– character cells / special support cells
Extracellular matrixExtracellular matrix
ProteinProtein FIBERSFIBERS – (collagen, elastic, reticular)– (collagen, elastic, reticular)
GROUND SUBSTANCEGROUND SUBSTANCE – gel-like arrangement of organic– gel-like arrangement of organic
materials where cells and fibers are embedded.materials where cells and fibers are embedded.
imparts strength and rigidity to the matriximparts strength and rigidity to the matrix
BLOOD VESSELSBLOOD VESSELS andand NERVE FIBERSNERVE FIBERS abound.abound.
Structural components:Structural components: Vary inVary in AMOUNTAMOUNT andand
COMPOSITIONCOMPOSITION which determine the physicalwhich determine the physical
properties of each CT type.properties of each CT type.
5. CONNECTIVE TISSUES: OriginCONNECTIVE TISSUES: Origin
MESODERMMESODERM:: mesodermal cells migratemesodermal cells migrate
from their site of origin and surround /from their site of origin and surround /
penetrate developing organs.penetrate developing organs.
MESENCHYMEMESENCHYME:: a derivative of mesoderma derivative of mesoderm
embryonicembryonic PRECURSORPRECURSOR of all connectiveof all connective
tissues.tissues.
Fibroblasts , chondroblasts, osteoblastsFibroblasts , chondroblasts, osteoblasts
All blood cells and blood vesselsAll blood cells and blood vessels
Cartilage, bones, ligaments, tendons, fasciae,Cartilage, bones, ligaments, tendons, fasciae,
musclesmuscles
8. CELLS of Connective TissuesCELLS of Connective Tissues
Fibroblasts / fibrocytes / reticular cells /
adipocytes
– derived from undifferentiated
mesenchymal cells.
- FIXED CELLS in CTs / remain in CTs
Mast cells, macrophages, and plasma cells
- originate from hematopoietic stem cells in the bone
marrow
- circulate in the blood
- WANDERING CELLS move to CTs, where they remain and
execute their functions.
9. Blood leukocytes - are TRANSIENT CELLS of
CTs also
- originate in bone marrow
- they usually migrate to CTs where
they reside for a few days and die.
10. Functions of Connective Tissue CellsFunctions of Connective Tissue Cells
Cell type Representative product or activity Function
Fibroblast,
chondroblast,
osteoblast
Production of fibers and ground substance Structural
Plasma cell Production of antibodies
Immunological
(defense)
Lymphocyte
(several types)
Production of immunocompetent cells
Immunological
(defense)
Eosinophilic
leukocyte
Participation in allergic and vasoactive reactions, modulation
of mast cell activities and the inflammatory process
Immunological
(defense)
Neutrophilic
leukocyte
Phagocytosis of foreign substances, bacteria Defense
Macrophage
Secretion of cytokines and other molecules, phagocytosis of
foreign substances and bacteria, antigen processing and
presentation to other cells
Defense
Mast cell and
basophilic
leukocyte
Liberation of pharmacologically active molecules (eg,
histamine)
Defense (participate in
allergic reactions)
Adipose (fat) cell Storage of neutral fats
Energy reservoir, heat
production
11. FIBROBLAST: Active and quiescent stagesFIBROBLAST: Active and quiescent stages
FIBROBLASTFIBROBLAST
- the dominant cells in the CT- the dominant cells in the CT
FIBROCYTESFIBROCYTES
Has an abundant and irregularly branchedHas an abundant and irregularly branched
cytoplasmcytoplasm
Nucleus is ovoid, large, and pale staining, withNucleus is ovoid, large, and pale staining, with
fine chromatin and a prominent nucleolus.fine chromatin and a prominent nucleolus.
Cytoplasm is rich in rERCytoplasm is rich in rER
Golgi complex is well developedGolgi complex is well developed
SynthesizeSynthesize collagen, reticular, andcollagen, reticular, and
elastic fiberselastic fibers
SynthesizeSynthesize constituents of theconstituents of the
extracellular matrix.extracellular matrix.
The spindle-shaped fibrocytes are smallerThe spindle-shaped fibrocytes are smaller
than the fibroblasts and are maturethan the fibroblasts and are mature
Less active cells of the fibroblast line.Less active cells of the fibroblast line.
It has fewer processesIt has fewer processes
Has a smaller, darker, elongated nucleus;Has a smaller, darker, elongated nucleus;
With acidophilic cytoplasmWith acidophilic cytoplasm
Has a small amount of rERHas a small amount of rER
13. MACROPHAGES or HISTIOCYTES
Derived from circulating blood MONOCYTES that
take up residence in the connective tissue.
PHAGOCYTIC cells that ingest bacteria, dead cells,
cell debris, and other foreign matter in the CT
Enhance immunologic activities of the lymphocytes.
ANTIGEN-PRESENTING CELLS (APC) to
lymphocytes and perform an important function in
the immune response
Macrophages have specific names in different
organs
14. Macrophage:Macrophage:
•usually appears round with irregular cell outlines, butusually appears round with irregular cell outlines, but
exhibits aexhibits a VARIABLE APPEARANCEVARIABLE APPEARANCE
• small nucleus rich in chromatin and cytoplasm filled withsmall nucleus rich in chromatin and cytoplasm filled with
dense,dense, INGESTEDINGESTED particles.particles.
•When a vital dye such as trypan blue or India ink isWhen a vital dye such as trypan blue or India ink is
injected into an animal, macrophages engulf andinjected into an animal, macrophages engulf and
accumulate the dye in their cytoplasm in the form ofaccumulate the dye in their cytoplasm in the form of
granules or vacuoles visible in the light microscopegranules or vacuoles visible in the light microscope
15. Distribution and Main Functions of the
Cells of the Mononuclear Phagocyte
System.
Cell Type Location Main Function
Monocyte Blood Precursor of macrophages
Macrophage
Connective tissue, lymphoid
organs, lungs, bone marrow
Production of cytokines, chemotactic
factors, and several other molecules that
participate in inflammation (defense),
antigen processing and presentation
Kupffer cell Liver Same as macrophages
Microglia cell
Nerve tissue of the central
nervous system
Same as macrophages
Langerhans cell Skin Antigen processing and presentation
Dendritic cell Lymph nodes Antigen processing and presentation
Osteoclast
Bone (fusion of several
macrophages)
Digestion of bone
Multinuclear
giant cell
Connective tissue (fusion of
several macrophages)
Segregation and digestion of foreign bodies
16. MAST CELLSMAST CELLS
oval to round CT cellsoval to round CT cells
10–13µm in diameter10–13µm in diameter
cytoplasm is filled withcytoplasm is filled with BASOPHILICBASOPHILIC secretorysecretory
granulesgranules
With centrally located small, spherical nucleusWith centrally located small, spherical nucleus
which is frequently obscured by the cytoplasmicwhich is frequently obscured by the cytoplasmic
granules.granules.
synthesize and releasesynthesize and release HISTAMINEHISTAMINE andand
HEPARINHEPARIN..
Exposure of mast cells toExposure of mast cells to ALLERGENSALLERGENS causescauses
rapid release of histamine and other vasoactiverapid release of histamine and other vasoactive
chemicals.chemicals.
17. Mast cells
LM EM
G - Granules containing histamine
and heparin
M – mitochondria
N – nucleus
E – elastic ; C- collagen fibrils
18. Mast cell secretion
(1) IgE molecules are bound to the surface receptors
(2) After a second exposure to an antigen (eg, bee venom), IgE molecules bound to surface receptors are cross-
linked by the antigen. This activates adenylate cyclase and results in the phosphorylation of certain proteins.
(3) At the same time, Ca2+
enters the cell.
(4) These events lead to intracellular fusion of specific granules and exocytosis of their contents.
(5) In addition, phospholipases act on membrane phospholipids to produce leukotrienes.
The process of extrusion does not damage the cell, which remains viable and synthesizes new granules. ECF-A,
eosinophil chemotactic factor of anaphylaxis.
19. ADIPOSE CELLS / ADIPOCYTESADIPOSE CELLS / ADIPOCYTES
Fixed cells in loose CTFixed cells in loose CT
Adipocytes are very long-lived cells. Their number isAdipocytes are very long-lived cells. Their number is
determined by the number ofdetermined by the number of LIPOBLASTLIPOBLAST (pre-(pre-
adipocyte) ) generated during fetal and earlyadipocyte) ) generated during fetal and early
postnatal development.postnatal development.
Function:Function: STORE FATSTORE FAT (lipid), provide(lipid), provide PROTECTIVEPROTECTIVE
packing material in and around numerous organs andpacking material in and around numerous organs and
for the production offor the production of HEATHEAT..
20. Adipocytes
• exhibits a narrow rim of cytoplasmexhibits a narrow rim of cytoplasm
• flattened, eccentric nucleusflattened, eccentric nucleus
• In histologic sections, the largeIn histologic sections, the large fat globulesfat globules of adipose cellsof adipose cells
have been dissolved by different chemicals, leaving a large,have been dissolved by different chemicals, leaving a large,
highly characteristichighly characteristic EMPTYEMPTY space.space.
21. PLASMA CELLSPLASMA CELLS
Derived fromDerived from B LYMPHOCYTESB LYMPHOCYTES that have beenthat have been
exposed to antigens.exposed to antigens.
Plasma cells producePlasma cells produce ANTIBODIESANTIBODIES of importanceof importance
in immune reactions.in immune reactions.
Large, ovoid cells that have aLarge, ovoid cells that have a BASOPHILICBASOPHILIC
cytoplasm due to their richness in roughcytoplasm due to their richness in rough
endoplasmic reticulumendoplasmic reticulum
Exhibits a smaller, eccentrically placed nucleus withExhibits a smaller, eccentrically placed nucleus with
condensed, coarse chromatin clumps distributedcondensed, coarse chromatin clumps distributed
peripherally in a characteristic radial (cartwheel)peripherally in a characteristic radial (cartwheel)
pattern and one central mass.pattern and one central mass.
22. Plasma cells
•A prominent,A prominent, CLEAR AREACLEAR AREA ((golgi complexgolgi complex) in the) in the
cytoplasm is adjacent to the nucleus.cytoplasm is adjacent to the nucleus.
• Golgi complex - is where theGolgi complex - is where the terminal glycosylationterminal glycosylation
of the antibodies (glycoproteins) occurs.of the antibodies (glycoproteins) occurs.
23. LEUKOCYTES
White blood corpuscles / white blood cells (WBC)White blood corpuscles / white blood cells (WBC)
WANDERINGWANDERING cells of the connective tissue.cells of the connective tissue.
Basophils, neutrophils, eosinophils, lymphocytes, monocytesBasophils, neutrophils, eosinophils, lymphocytes, monocytes
macrophagemacrophage
The normal CT contains leukocytes that migrate through theThe normal CT contains leukocytes that migrate through the
walls of blood vessels from the blood to CT by a processwalls of blood vessels from the blood to CT by a process
calledcalled DIAPEDESISDIAPEDESIS..
Neutrophils and MonocytesNeutrophils and Monocytes
secretesecrete ENZYMEENZYME that degrade the basement membranethat degrade the basement membrane
between the endothelial cells – to squeeze into the site ofbetween the endothelial cells – to squeeze into the site of
infectioninfection DIAPEDESISDIAPEDESIS
WBCs must aggregate in the CT area to mediateWBCs must aggregate in the CT area to mediate
INFLAMMATORYINFLAMMATORY process.process.
24. Fig. 1. Leukocyte extravasation is controled by a cascade of adhesion andFig. 1. Leukocyte extravasation is controled by a cascade of adhesion and
signalling molecules. First leukocytes are captured to the blood vessel wall bysignalling molecules. First leukocytes are captured to the blood vessel wall by
selectinsselectins. Sensing chemotactic factors such as. Sensing chemotactic factors such as chemokineschemokines on theon the
endothelial cell surface leads to the activation of leukocytes and leukocyteendothelial cell surface leads to the activation of leukocytes and leukocyte
integrinsintegrins. Finally leukocytes migrate along the blood vessel wall and through. Finally leukocytes migrate along the blood vessel wall and through
the endothelial cell layer and the underlying basal lamina.the endothelial cell layer and the underlying basal lamina.
Source: http://celldynamics.uni-muenster.de/Projects/ProB1txt.htmlSource: http://celldynamics.uni-muenster.de/Projects/ProB1txt.html
DiapedesisDiapedesis
25. Increased vascular permeability
caused by the action of vasoactive substances
Ex. Histamine - from mast cells and basophils
vascular permeability
Increases in blood flow
responsible for local swelling (edema), redness, and heat.
Pain is due to chemical mediators on nerve endings.
Chemotaxis – when specific cell types are attracted
by some molecules, is responsible for the migration of
large quantities of specific cell types to regions of
inflammation.
leukocytes cross the walls of venules and capillaries by
diapedesis, invading the inflamed areas.
26.
27. Leukocytes
• NeutrophilsNeutrophils - active and powerful- active and powerful PHAGOCYTESPHAGOCYTES;;
they engulf and destroy bacteria at sites of infections.they engulf and destroy bacteria at sites of infections.
• EosinophilsEosinophils - become active and increase in- become active and increase in
number afternumber after PARASITICPARASITIC infections orinfections or ALLERGICALLERGIC
Section of an inflamed
intestinal lamina propria.
Inflammation was caused by
nematode parasitism.
Aggregated eosinophils and
plasma cells function mainly
in the CT by modulating the
inflammatory process.
Giemsa stain. LPO
28. CT Component: EXTRACELLULAR MATRIX
- GROUND SUBSTANCE
fills the space between cells & fibers of the CTfills the space between cells & fibers of the CT
a highlya highly HYDRATEDHYDRATED, colorless, and transparent, colorless, and transparent
complex mixture of macromolecules.complex mixture of macromolecules. (Water, salts
and other low molecular substances &
proteoglycans) VISCOUSVISCOUS..
Acts as both a lubricant and aActs as both a lubricant and a barrierbarrier to theto the
penetration of invaderspenetration of invaders
30. Glycosaminoglycans, GAGsGlycosaminoglycans, GAGs
(Acid mucopolysaccharides)(Acid mucopolysaccharides)
LINEAR POLYSACCHARIDES formed by
repeating disaccharide units that are bound
covalently to proteoglycan molecule.
intensely hydrophilic and act as polyanions
Heparan sulfateHeparan sulfate
Keratan sulfateKeratan sulfate
Dermatan sulfateDermatan sulfate
Chondroitin sulfateChondroitin sulfate
Hyaluronic acidHyaluronic acid
31. The core protein associated with the four main GAGs
CARBOHYDRATE moiety predominates (80-90%)
bind to a great number of cations (usually sodium) by
electrostatic (ionic) bonds
intensely hydrated structures with a thick layer of
SOLVATION water surrounding the molecule – VISCOUS
act as a barrier to the penetration of bacteria and other
microorganisms
Purposes:
Act as STRUCTURAL components of the extracellular
matrix
ANCHORING cells to the matrix
Bind many protein growth factors (eg, transforming growth
factor, TGF-, of fibroblasts).
GAG + Protein core = PROTEOGLYCANS
32. Proteoglycan
EXTRACELLULAR
proteoglycans
In the matrix
Ex. Aggrecan (in cartilage)
SURFACE proteoglycans
attached to the surface of
many types of cells,
particularly epithelial cells.
Ex. syndecan and
fibroglycan
33. GLYCOPROTEIN
Globular PROTEIN
molecules to which
branched chains of
MONOSACCHARIDES are
covalently attached.
Protein moiety usually
predominates
play an important role in the
INTERACTION between
neighboring adult and
embryonic cells
For the adhesion of cells to
their substrate
Ex. Fibronectin
- has binding sites for cells, collagen,
and GAGs.
- help to mediate normal cell
adhesion and migration
34. TISSUE FLUID
Very small quantity of fluid in the extracellular matrix
(ECM) of CTs that comes from the BLOOD
Due to HYDROSTATIC pressure of the blood, small
amount of plasma fluid passes through the capillary
walls.
Since CTs are widely distributed, as much as one-third
of the plasma proteins of the body are STORED in the
ECM of the connective tissue.
EDEMA – in pathological conditions, it is promoted by
the accumulation of water in the extracellular spaces
due to increased VASCULAR permeability.
35. Movement of fluid through connective tissue.
There is a decrease in hydrostatic pressure and an increase in osmotic
pressure from the arterial to the venous ends of blood capillaries (upper
part of drawing). Fluid leaves the capillary through its arterial end and
repenetrates the blood at the venous end. Some fluid is drained by the
lymphatic capillaries.
36. A. CT fibersA. CT fibers
1) Collagen fibers1) Collagen fibers
Dominant fiber type in most CT.Dominant fiber type in most CT.
OrgansOrgans: Throughout the body: Throughout the body
FxnFxn: Add strength to the CT.: Add strength to the CT.
Component:Component: Microfibrils (collagen fibrils) which areMicrofibrils (collagen fibrils) which are
assemblies of tropocollagen (ofassemblies of tropocollagen (of AAs: hydroxyprolineAAs: hydroxyproline
and hydroxylysine).and hydroxylysine).
TypesTypes I, II and III tropocollagens are the major fiberI, II and III tropocollagens are the major fiber
formers.formers.
Tropocollagen IV is an important structuralTropocollagen IV is an important structural
component of thecomponent of the BASAL LAMINABASAL LAMINA..
37.
38. Medical significance:
KELOIDKELOID – abnormal amount of collagen fibers– abnormal amount of collagen fibers
formed in the scars of the skin.formed in the scars of the skin.
SystemicSystemic SCLEROSISSCLEROSIS – excessive accumulation of– excessive accumulation of
collagen in skin, digestive tract, kidneys – hardenedcollagen in skin, digestive tract, kidneys – hardened
and dysfunctional impairment of organs affectedand dysfunctional impairment of organs affected
(fibrosis).(fibrosis).
39. Vitamin C deficiency (Vitamin C deficiency (SCURVYSCURVY) – hydroxylation of) – hydroxylation of
prolyl and lysyl residues (AAs) in the endoplasmicprolyl and lysyl residues (AAs) in the endoplasmic
reticulum can be inhibited, producing defectivereticulum can be inhibited, producing defective
collagen (non-reversible) –collagen (non-reversible) – DEGENERATIONDEGENERATION ofof
connective tissue.connective tissue.
Vit. C is aVit. C is a COFACTORCOFACTOR of proline hydroxylase.of proline hydroxylase.
40. 2) Reticular fibers
Very delicate and form fine networks instead of thickVery delicate and form fine networks instead of thick
bundles.bundles.
Affinity with special stains.Affinity with special stains. Ex:Ex: SILVERSILVER stainedstained
sections reticular fibers look like fine,sections reticular fibers look like fine, blackblack threads.threads.
Their different staining characteristics were initiallyTheir different staining characteristics were initially
thought that reticular fibers were completelythought that reticular fibers were completely
different from collagen fibres.different from collagen fibres.
Component:Component: TypeType IIIIII collagencollagen
Fxn:Fxn: Support to individual cells of Muscle & AdiposeSupport to individual cells of Muscle & Adipose
tissues andtissues and CAPSULATEDCAPSULATED organs (liver & spleen);organs (liver & spleen);
tunica media of muscular arterytunica media of muscular artery
43. 3) Elastic fibers
• In fresh tissuesIn fresh tissues: Light yellow in large amounts in the: Light yellow in large amounts in the
tissue.tissue.
• Special stains:Special stains: Resorcin fuchsinResorcin fuchsin gives a dark violetgives a dark violet
color.color.
• ComponentComponent:: The matrix accounts for about 90% ofThe matrix accounts for about 90% of
the fiber and composed ofthe fiber and composed of elastinelastin and microfibrils.and microfibrils.
Both elastic fibers and microfibrils are not collagen..Both elastic fibers and microfibrils are not collagen..
• Organs:Organs: Elastic ligaments of the vertebral column;Elastic ligaments of the vertebral column;
ear auricles; skin dermis; aorta; large arteriesear auricles; skin dermis; aorta; large arteries
44. •Can be stretched to about 150% of their original length. Elastin fibersCan be stretched to about 150% of their original length. Elastin fibers
remains unfolded as a "random coil".remains unfolded as a "random coil".
• They resume their original length if the tensile forces applied to theThey resume their original length if the tensile forces applied to the
elastic fibers are relaxed.elastic fibers are relaxed.
• Fibers are cross-Fibers are cross-
linked to eachlinked to each
other byother by desmosindesmosin
andand isodesmosinisodesmosin
found betweenfound between
elastin molecules.elastin molecules.
47. References:
Junquiera LC, Carneiro J. 2005. BASIC HISTOLOGY :
TEXT AND ATLAS 11th
Edition. McGraw-Hill’s ACCESS
MEDICINE.
Young B. 2009. WHEATER’S FUNCTIONAL HISTOLOGY.
5TH
Edition. UK: Churchill Livingstone. Distributor: Phils:
C & E Publishing, Inc.
