L4 Connective Tissues

7/24/2019 L4 Connective Tissues

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Prof. Marina KapitonovaProf. Marina Kapitonova

ecture:

CONNECTIVE TISSUE

for Year 1 Medical Students of UiTM



The objectives:

1.Describe connective tissue with

regard to its classification.

2.Describe the cells and thematrix of the connective tissue

with regards to their structureand function.



Connective tissue is a tissue of mesenchimal origin which connects,

holds and supports other bod tissue.

II. DEFINITION OF

CONNECTIVE TISSUE

fat cells

lmphocte

f ibr oblast

collagen

fiber

plasma

cell

capillar

pericte

mast cell

elastic fibers

neutrophil

histiocte

!macrophage"

capillar



###. D#$%#&C%#'( )(*%+($ -) C-&&(C%#'( %#$$+($

1. -n the contrar to other tissues, connective tissue is composed

mostl of extracellular matrix with a limited amount of cells

scattered throughout the matrix.

2. Cells maintain their associations with the extracellular matrix bforming specialied /unctions that hold them to the surrounding

macromolecules.

0. %he extracellular matrix of connective tissue is composed of a

hdrated gellie ground substance with fibers embedded in it.



protection against infection and other foreign material

!immunoctes"

regeneration after in/ur !fibroblasts"

IV. FUNCTIONS OF THE CONNECTIVE TISSUE

- mechanical support !fibers"

- exchange of metabolites between blood and tissue !ground

substance"

- storage of reserve energ material !adipose cells"



ocalization

ocalization

of Epithelium

f Epithelium

& Connective

Connective

Tissue in theissue in the

Human Body

uman Body

protective

secretorabsorptive

reproductive

sensor

lubricative

excretor

epithelial

tissue

connective

tissue

bonecartilage

ligaments

tendons

loose and dense

connective tissues

adipose tissue



CO!O"#T#O$ O% CO$$ECT#E T#""'E

1. CONNECTIVE TISSUE = CES ! E"T#$CEU$#

M$T#I"

%. E"T#$CEU$# M$T#I" = &#OUND

SU'ST$NCE ! FI'E#S

(. M$C#OMOECUES OF THE &#OUND

SU'ST$NCE = &$& ! )#OTEO&YC$NS ! $DHESIVE

&YCO)#OTEINS



C (""#%#C(T#O$ O% CO$$ECT#E T#""'E

(""#%#C(T#O$ O% CO$$ECT#E T#""'E

Connective Tissue

Connective %issueConnective %issue

Proper Proper !fibrillar"!fibrillar"

Connective %issue

with $pecial Properties$upporting C%

*dipose*dipose

eticular

3ematopoetic !4 5M"

Pigment

Mucous

4oose

!areolar"

Dense

egular

!collagenous,

elastic"#rregular

CartilageCartilage

6one



Classification of the

lassification of the

Connective Tissue

onnective Tissue

Cells

ells

C% cells can be characteried as

fixed or wandering.

fibroblasts and a closel relatedtpe mofibroblasts,

macrophages,

adipose cells,

mast cells,

undifferentiated mesenchimal

cells !adventitial cells, perictes".

%he cells that comprise the

wandering !transient"

lmphoctes,

plasma cells,neutrophils,

eosinophils,

basophils,

monoctes.

fat cells

fibroblastmacrophages

collagen

plasma

cells

mast cell

P

e

r

pericte

elastic

fiber

endothelial cell



T)!E" O% CE "

#$ OO"E (*EO (* T#""'E

1. esident

fibroblasts

macrophages

mesenchmal cells

reticular cells

fat cells

mast cells

2. 'isitant

plasma cells

neutrophils

lmphoctes

leuoctes !neutrophils,

lmphoctes, etc"

pigment cells



CO!O"#T#O$ O% +*O'$, "'B"T($CE

O!O"#T#O$ O% +*O'$, "'B"T($CE

water – mineral salts – GAG - glycoproteins 7 proteoglcans

8*8s

&onsulfated group

-Hyaluronic acid (in skin, loose connective tissue, break down with

umbilical cord, vitreous body, & synovial fluid hyaluronidase

spreading factor!

-"hondroitin (in cornea & embryonic cartilage#

$ulfated group

-"hondroitin-$-sulfate (in cornea, skin, bone & cartilage#

-"hondroitin-%-sulfate (in tendons, cartilage, umbilical cord & intervertebral disks#

-ermatan sulfate (in skin, tendons, ligaments & heart valves#-'eratan sulfate (in bone, cartilage, cornea & intervertebral disks#

Collectivel termed 9glcosaminoglcans:

8round - controls passage of pathogens

substance

functions - allows diffusion of ) & nutrients



%his permits the rapid spread of bacteria through the

connective tissue spaces. Permeabilit ofmicrovessels ma increase under certain conditions

!inflammation, liberation of the biologicall active

substances such as histamine and bradinin".

C #$#C( CO**E (T#O$":

Man pathogenic bacteria, such as $taphlococcus

aureus, secrete haluronidase, an enme that

cleaves haluronic acid !it ma be up to 2;

micrometer long" into numerous small fragments,

thus converting gel state of extracellular matrix intoa sol state.



%hese large structures loo lie a bottle brush, with

the protein core resembling the wire stem and the

various sulfated 8*8s pro/ecting from its surface in

threedimensional space, as do the bristles of thebrush.

!*OTEO+ )C($":

Proteoglcans constitute a famil of

macromolecules< each is composed of a protein core

to which glcosaminoglcans are covalentl bound.



Sc*e+atic

Dia,ra+ of

$ssociation of

$,,recanMolecules -it*

Colla,en Fiers.

collagen fibres haluronic acid

molecule

haluronic

acid

lin proteincore protein

chondroitin

sulphate

proteoglcan

collagen tpe ##



COO$

!*OTEO+ )C($"

Name Approx.Molecular Weight

Type of GAGMonomers

Approx . No. ofGAG

Chain

Distribution Function

Decorin =;,;;; Chondroitinsulfate,

dermatansulfate

1 >idedistribution in

connectivetissue

6inds tpe #collagen and

%8)

*ggrecan 21;,;;; Chondroitinsulfate,

eratan sulfate

10; Cartilage *ggregateswith

haluronan,supportive

function

Perlecan ?;;,;;; 3eparansulfate

21@ 6asal laminae )ilteringfunction

6etaglcan 0?,;;; Chondroitinsulfate,dermatan

sulfate

1 Cell surface,(xtracellularmatrix

6inds%8)

$ndecan1 02,;;; Chondroitinsulfate,heparansulfate

10 $urface offibroblast andepithelial cells

Cell adhesion,binds )8)



%he ma/or tpes are fibronectin, laminin, entactin, tenascin,

chondronectin and osteonectin.

+ )CO!*OTE#$":

%he abilit of cells to adhere to components of the extracellular

matrix is mediated b cell adhesive glcoproteins.

%hese large molecules have several domains, at least one of

which usuall binds to cell surface protein called integrins, one

to collagen fibers, and one to proteoglcans.



%#BE*":

1. Collagen and elastic fibers, the two ma/or fibrous proteins ofconnective tissue, have distinct biochemical and mechanical

properties as a conseAuence of their structural characteristics.

2. %he provide tensile strength and elasticit to thissubstance.

0. Classical histologists have described three tpes of fibers

although it is now nown that reticular fibers are in fact a tpe

of collagen fibers but the term reticular fibers is retained.



SEM of Colla,en Fier 'undles in t*e E/ineuriu+. 0 %222



Colla-en %ibrils .ith /0 nm !eriodicity of

"triations1 TE2 344244451

#n (M the collagen fibrils exhibit a banding pattern with an axial

periodicit of ?B nm. -verlapping of tropocollagen molecules is

responsible for banding pattern. %ropocollagen molecules lie

parallel to each other overlapping b of their length.



Colla-en %ibers



%ormation of Colla-en by %ibroblasts

Molecule of preprocollagen translated in the ( undergoesMolecule of preprocollagen translated in the ( undergoes

hdroxlation, glcoslation and formation of procollagen tripplehdroxlation, glcoslation and formation of procollagen tripple

helix in the (.helix in the (.

collagen fiber

reticular

fibers

unit fibril ofcollagen

glcine

proline

polpeptide chain

addition of

carbohdrate

tropocollagen

procollagen

peptidase

procollagen



The "tructure of the "uperheli5 of Colla-en

he "tructure of the "uperheli5 of Colla-en

!olypeptide Chain

olypeptide Chain

.

%hese collagen molecules !whichare also called tropocollagen" self

assemble into protofilaments,

which are filaments of @ nm

diameter.

triple helix of

threepolpeptide

chains

collagen

molecule

staggered

collagen

molecules

assemble

into a fibril

fibril

banding

pattern



Colla-en

%ibers

$chematic representation of the components of a C). %he

ordered arrangement of the tropocollagen molecules gives rise to

the gap and overlap regions, responsible for ?Bnm crossbanding of

tpe # collagen.

muscle

bundle

tendon

fiber fibril



Types of

Colla-en

Collagen Type Location Cells ro!ucing Characteristics

%pe # !;E"!composed of twotpes of Fchain"

Dermis of sin,tendon.4oose !areolar",

dense ordinarconnective tissue,collagen fibers.Most wideldistributed tpe ofcollagen in internalorgans. 6one.

Dentin !teeth".

)ibroblasts.

eticular cells and

smooth muscle

-steoblasts

-dontoblasts

4ow hdroxlsine,low carbohdrate!broad fibrils"

%pe ## !composedof onl one tpe ofFchain"

3aline and elasticcartilage'itreous bod ofee, intervertebraldisc

Chondroctesetina cellsChondroctes

3igh hdroxlsine,high carbohdrate!thinner fibrils thantpe #"

%pe ### !composedof onl one tpe ofFchain"

4oose connectivetissue< reticularfibers, papillarlaer of dermis,!found earl indevelopment"

6lood vessels

)ibroblasts andreticular cells$mooth musclecells, endothelialcells

3ighhdroxproline, lowhdroxlsine, lowcarbohdrate



Types of

Colla-en

Collagen Type Location Cells ro!ucing Characteristics

%pe #' !composedof two tpes of Fchain"

6asal lamina4ens capsule of ee

(pithelial andendothelial cells4ens epithelium

'er highhdroxlsine, highcarbohdrate!retains procollagenextension peptides"

%pe ' )etal membranes

!placenta"6asementmembranes6one, $moothmuscle

)ibroblasts

(pithelial cells-steoblasts$mooth musclecells



CO (6

+E$O'"

CO$$ECT#E

T#""'E

Tendo

calcaneus

7tendon of

(chilles8

lon-itudinal

section2 H &

E2 53/91

fibrocte

nucleicollagen



$ome individuals, especiall blacs, are predisposed

to an excessive accumulation of collagen during

healing. #n these patients the scar forms an elevated

growth nown as a eloid.

C #$#C( CO**E (T#O$":

*t the end of surger, the cut surfaces of sin are

carefull sutured< usuall a wee later the sutures

are removed. %he tensile strength of the dermis at

that point is onl about 1;E that of normal sin.

>ithin the next = wees, the tensile strength

increases to about G;E of normal, but in man cases

it never reaches 1;;E. %he initial weaness isattributed to the formation of tpe 0 collagen during

earl wound healing, whereas the later improvement

in tensile strength is due to scar maturation, when

tpe ### collagen is replaced b tpe # collagen.



6ecause these two structures are responsible for

maintaining teeth in their socets, the smptom ofscurv include bleeding gums and loose teeth. #f the

vit * deficienc is prolonged, other sites are also

affected. %hese smptoms ma be alleviated b

eating foods rich in vitamin C.

C #$#C( CO**E (T#O$":

3droxlation of proline residues reAuires the

presence of vit C. #n individuals who suffer from a

deficienc of this vitamin, the alphachains of the

tropocollagen molecules are unable to form stable

helices, and the tropocollagen molecules are

incapable of aggregating into fibrils. %his condition,

nown as scurv, first affects C% with high turnoverof collagen, such as periodontal ligaments and

gingivae.



Elastic (rtery2 Orcein2 5 39



Elastic %ibers

%he are

manufactured b fibroblasts

of connective tissue and b

smooth muscle cell of blood

vessels. %he are composedof elastin, a protein rich in

glcine and lsine.

fat

cells

fibroblastmacrophages

collagen

plasma

cells

mast cell

Pe

r

pericte

elastic

fiber

endothelial cell



E$STIC FI'E#S

In H 3 E stained tissues 4c5 elastic fiers 4E5 stand out as ,lass6

ri,*t /in78stained structures ta7in, u/ acidic d6es suc* as eosin

-it* +uc* ,reater a9idit6 t*an CF 4F firolsts5.

EF can e stained 6 s/ecial tec*ni:ues. In t*is e0a+/le EF 4E5 in

t*e der+is of t*e s7in are stained lue 6 toluidine lue 4d5 and

contrast -it* /ale8stainin, colla,en.

(

)(

C



Elastin is a /rotein

-*ic* asse+les

into stretc*ale andresilient fiers and

s*eets 3 is t*e +ain

co+/onent of EF.

E$STIN

relaxedrelaxed !random coil"

random coil

conformation

stretched

relaxednew

random

coil

conform

ation

stretched

Elastic Fiers



In EF ,l6co/rotein +icrofila+ents 4firillin5 surround and

or,ani;in, a core re,ion of crossed8lin7ed elastin.

Elastic Fiers

Dia8

,ra+T

E

M

elastin

core

microfibrills

M

(



(orta2

Human2

;ei-ert<s

elastic

tissue stain

and

phlo5ine2

3/9 51

tunica intima

elastic fibers

tunica media

smooth muscle

tunica adventitia

vasa vasorum



People who have MarfanHs sndrome are unusuall

tall, have a ver wide arm span, are prone to develop

subluxation of lens and are also prone to develop

fatal rupture of aorta. %he absence of fibrillin which

interacts with elastin in tissues provoes lens

dislocates, as its suspensor fibers normall containfibrillin. * lac of elastin recoil in aorta would weaen

the wall 5 predispose to rupture. %he growth of long

bones is somewhat constrained b the presence of

fibrillin, and hence bones grow longer in its absence.

C #$#C( CO**E (T#O$":

%he integrit of elastic fibers depends on the

presence of microfibrils. Patients with Marphan

sndrome have a defect in the gene on chromosome

1@ that codes for fibrillin< therefore their elastic fibers

do not develop normall.



*eticular %ibers2 TE2 94244451

eticular fibers do not gather into bundles as do collagenous

fibers but tend to form delicate networs.



*eticular %ibers

) cannot be seen in 3 5 ( sections, but can be stained b silver

impregnation methods or b P*$ reagent. #n this microphotograph, ) is

a lmph node are seen as fine blac lines, with lmphoid cells stained red in

the bacground. ', vessel.



Connective Tissue Cells

%hefibroblasts are

the most

abundant cell

tpe in the C%.

%he are

responsible for

the snthesis

of almost all of

the extra

cellular matrix.



Cell ines ,erived from esenchyme

Cells

%he

Mesenc*6+e cells can /otentiall6 de9elo/ into a

9ariet6 of cells -*ic* +a7e u/ different tissue t6/es.



"chematic ,ia-ram of the Ori-ins of Cells of

Connective Tissue

+ndifferentiated

mesenchmal cell

-steoblast(ndothe

lial

cell

Mesothelial

cell)ibroblast

*dipocte

Chondroctes -steocte

Chondroblast

6 lmphocte

Plasma cell

3emapoietic

$tem cell 6C

Monocte

Macrophage

-steoclast Megaarocte

Mast cell

&eutrophil

(osinophil

6asophil



CE " O% CO$$ECT#E T#""'E

Cells General Functions

)ibroblast Produces fibers !collagen, reticular, elastin" and amorphous /ellies !glcosaminoglcans, proteoglcans"

Macrophage Phagoctic !e.g., bacteria"*ntigen presentation$ecretor !e.g., interleuinl, interferonI"

Pericte Differentiate into fibroblasts, reticular cells, smooth musclecell in blood vessel, adipoctes

Mast cell $ecrete heparin, histamine, slowreacting substance ofanaphlaxis, eosinophilic chemotactic factor of anaphlaxis

)oreign bod giantcell

Phagoctic !larger particulate material"

eticular cell Produce reticular fibers !tpe ### collagen" for lmph nodes,

spleen, bone marrow, etc.

*dipoctes )at storage, mobiliation

Chondroblast!chondrocte"

$ecrete collagen or elastic fibers, as well as cartilageamorphous intercellular substances !glcosaminoglcan,proteoglcan", and other proteins

-steoblasts $ecrete collagen, bone matrix !proteoglcans"



%ibroblasts and Colla-en

*

+

+

"



%ibroblasts and Colla-en2 TE2

5942444

)ibroblasts maoccur either in active or

Auiescent state

!fibroctes".



oose Connective Tissue Cells

oose Connective Tissue Cells

%he macrophages phagoctose foreign substances and

damaged and senescent cells as well as cellular debris< the also

assist in the initiation of the immune response.



Macrophage,

TE2

5942444

Macrophages belong to the mononuclear phagocting

sstem and are subdivided into two groups of cells, phagoctes and

antigenpresenting cells.

$tem cells



The

acropha-e

"ystem

*ll its members

arise from a common stem cell in

the bone marrow, possess

lsosomes, are capable of

phagoctosis, and displa

receptors for antibidies and

complement.

$tem cells

Monoblasts !in bone marrow"

Promonoctes

Monoctes !in circulating blood"

Macrophages !in tissue and organs< both free

and fixed, unless noted otherwise"

4ining lmph sinuses

J lmph nodes

4ining blood sinuses or sinusoidsJ liver !fixed Kupffer cells"

J spleen !splenoctes or

hemophages"

J bone marrow

4ining serous cavities !pericardial,

peritoneal, and pleural"

*reolar connective tissue !fixed histioctes"

4ung !alveolar macrophages or dust cells"

Circulating blood !monoctes"

Central nervous sstem !fixed mocroglia or

mesoglia"

oint cavities !tpe * snovial cell"

6one !osteoclasts"

Macrophage $stem



p g Name of Cell Function "s# Location

Macrophage Phagoctosis,antigen presentation

4oose !areolar" connective tissue

Peritoneal or pleural

macrophages

Phagoctosis $erous cavities

Macrophage 6lood cell destruction, antigenpresentation

6one marrow, $pleen, %hmus,4mph node

*lveolar macrophage !ordust cell"

Phagoctosis *lveoli of lung

4angerhans cell *ntigen presentation (pidermis

Kuppfer cell Phagoctosis 4iver !perinsinusoidalmacrophage"

Microglia Phagoctosis,antigen presentation

Central nervous sstem

-steoclast !multinucleate" 6one resorption 6one surfaces !form from fusion ofmonoctederived macrophages"

)ibroblastderivedmacrophage

Phagoctosis #ntestinelamina propria+terusendometrium

)oreign bod giant cell!multinucleate"

Phagoctosis induced in areas of particulatematerial !e.g., talc on mesenter"

!fusion of monoctes, macrophages"



(lveolar

acropha-es

2

"E2

/244451



!eritoneal

acropha-es

2

"E2

34244451

Criteria for designating macrophagesL

1"avidl phagoctic

2"strong affinit for des and particulates

0"store particulates

="adhere to glass surfaces in culture@"have antibod receptor sites on cell membranes

Connective tissue cells M*$% C(44



undifferentiaited

cell

osteoblast chondroblastendothelial

cell

mesothelial

cell fibroblast

adipocte

osteocte chondroctes

hematopoietic

stem cell

6 lmphocte

plasma cell

monocte

macrophage

osteoclastmegaarocte

mast

cell

basophil

eosinophil

neutrophil6C



ast Cell

Human2

TE2

34244451

.

.Mast cells /ro+ote i++ediate *6/ersensiti9it6

reactions 4*a6 fe9er ast*+a ana/*6la0is5 follo-in, t*eir

release of secretor6 ,ranules -it* *e/arin and *ista+ine

-*ic* act as c*e+ical +ediators.



ast Cell

Human2

TE2

34244451

.

.

Mast cells are a+on, t*e lar,est of fi0ed cells of t*e CT

t*e6 are %28(2 +c+ in dia+eter. T*e /resence of nu+erous,ranules in t*e c6to/las+ is t*e identif6in, c*aracteristic of

+ast cells.



ast Cell

Human2

TE2

34244451

.

.

Mast cells /ossess *i,*8affinit6 cell8surface Fc rece/tors4Fc8e/silon#I5 for I,E. Cross8lin7in, of t*eir surface I,E

+olecules 6 anti,en causes t*eir clu+/in, and t*is tri,,eres

+ast cell de,ranulation -it* release of se9eral +ediators of

aller,ic reaction.



ast Cells1

a8 human2 H

& E2 53/9

b8 rat2tolui6

dine blue2

53=3/

Mast cells are found

in areolar C% and

along the course of

small blood

vessels.

mast

cells

collagen

elastic

fiber

fat

cell



'ictims of asthma attacs suffer from difficult in

breathing as a result of bronchospasm caused b

leuotriens released in the lungs.

C #$#C( CO**E (T#O$":

'ictims of ha fever attacs suffer from the effects of

histamine being released b the mast cells of the

nasal mucosa, which causes localied edema from

increased permeabilit of the small blood vessels.

%he swelling of the mucosa results in feeling 9stuffedup: and hinders breathing .



Cells of the oose Connective Tissue

ells of the oose Connective Tissue

%he plasma cells have eccentric nucleus with spoelie

distribution of heterochromatin in the nucleus.

fat cells

fat

loose connective

tissue

fatfat cell droplets of fat

*

6

C plasma cells mast cells



!lasma cell2 TE2 53>2444

lasma cell2 TE2 53>2444



!lasma Cells2

amina !ropria2

?ejunum2 5/39

cartwheel

nucleus

8olgi one

lmphoctes

basophilic

ctoplasm

eosinophil



$eutrophil2 TE2 5342444

eutrophil2 TE2 5342444

&eutrophils phagoctose and digest bacteria in areas of

acute inflammation resulting in formation of pus, an accumulation of

dead neutrophils and debris.

&

&

&



ymphocyte2 TE2 5342444

ymphocyte2 TE2 5342444

4mphoctes are present in small numbers in most C%,4mphoctes are present in small numbers in most C%,

except at sites of chronic inflammation where the are abundant. & 7except at sites of chronic inflammation where the are abundant. & 7

nucleus of the lmphocte.nucleus of the lmphocte.

&



*dipoctes ma be unilocular !white C%" or multilocular !brown C%".

CO$$ECT#E T#""'E CE "1 (,#!OC)TE"1

O$$ECT#E T#""'E CE "1 (,#!OC)TE"1

adipocte

fibroblast

macrophages

collagen

Plasma

cells

Mast cell

P

e

r

pericte

(lastic

fiber

endothelial cell



De9elo/in, Fat Cell

TEM 0(222



%(T CE 2

'nilo6

cular2

TE2

3>2444



B*O;$ %(T

ediasti6

num2

*hesus

mon@ey2

H1 & E12

(1 3/9 5A

B1 B1 /39 51

6rown fat is an uncommon variet of human fat found in the

upper bac !interscapular region" of the bod. +nlie the more

common white fat, brown fat cells contain a number of small lipid

droplets, hence the name multilocular fat. >hite fat cells, in contrast,

contain a single lipid droplet.

lobule of

polgonal

brown

fat cells

multilocular

fat cells

lipid

droplets

capsule



*ET#C' (*

CE "

ymph node

subcapsular

sinus1 *hesus

mon@ey2

H1 & E12 /39

51

lmphoctes

macrophage

reticular

cell

processes

capsule

reticular

cell

nucleus

reticular

cells



E"E$6

CH)E

%etal pi-

H1 & E12

B1 >> 5A

C1 994 51

Mesenchmal cells can differentiate into most of the adult

connective tissue cell tpes, includingL !1" fibroblasts, !2"

chondroblasts, !0" osteoblasts, !=" odontoblasts, !@" reticular cells,

and !?" adipoctes.

#n this plate, note several of the mature cell tpes that have

differentiated from mesenchmal cells. (xamine the developing hair

follicles in 6.

developing

hair

follicles

*

e

s

e

nc

h

y

m

e

mesenchme

mesenchmal

cells

developing

striated

muscle



'CO'"

CO$$ECT#

E T#""'E

'mbilical

cord2

on@ey2

H & E2

/391

fibroblasts

collagenous

connective

tissue

$#EO$# CONNECTIVE TISSUE Sucutaneous #at H3 E 0 <1%.



elastic

fibers

lmphocte

mast

cell

fibroblasts

collagenous

fibers

Documents

L4 Connective Tissues