Connective Tissue: Difference between revisions

Latest revision as of 19:11, 21 December 2023

Components and Classification[edit | edit source]

Connective tissue forms a matrix that supports and connects other tissues and organs. Below is an overview of its components:

Cells
- Resident (fixed)
- Transient (wandering)
ECM
- Fibers
- Amorphous ground substance

Connective tissue types belong to three main categories:

Connective tissue proper
- loose
- dense irregular
- dense regular
Embryonic connective tissue
- mesenchyme
- mucoid
Specialized connective tissue
- reticular
- adipose
- elastic
- cartilage
- bone
- blood

Types of the cells of connective tissue[edit | edit source]

Fixed cells[edit | edit source]

Reside within connective tissue. Derived from mesenchyme.

Fibroblasts[edit | edit source]

Fibroblasts function in synthesis and degradation of the ECM. Therefore, DNA is in euchromatin form, and the RER and Golgi apparatuses are abundant. Fibrocytes are "retired" fibroblasts that do not synthesize much.

Reticular cells[edit | edit source]

Similar to fibroblasts, produce reticular fibers. Note: Reticular cells ≠ reticulocytes! Reticulocytes are immature RBCs.

Adipocytes[edit | edit source]

Univacuolar
- spherical cell
- one large vacuole (stores triacylglycerols) takes up most of the space
- cytoplasm, flattened nucleus and other organelles are pushed to the periphery of the cell
- major component of white adipose tissue
  - energy storage
  - also functions in hormone production (adipokinins, leptins)
  - highly vascularized
Multivacuolar
- multiple smaller fat droplets
- nucleus is more central
- burns fat to heat via mitochondria, functions in thermoregulation
- major component of brown adipose tissue
  - more abundant in fetuses, neonates and small children
  - found primarily between scapulae, in axilla, mediastinum, and retroperitoneum

Pigment (melanin) cells[edit | edit source]

irregularly shaped
arise from neuroectoderm rather than mesenchyme
synthesize and store melanin

Schematic comparison of all fixed cells here.

Wandering cells[edit | edit source]

Formed in red bone marrow from hemocytoblasts, enter connective tissue via bloodstream.

Macrophages[edit | edit source]

variable shape with protrusions
kidney-shaped nucleus
phagocytose debris, damaged, or foreign cells
mainly in sparse connective tissue along capillaries

Plasma cells[edit | edit source]

eccentrically placed nucleus, alternating heterochromatin and euchromatin
large amount of cytoplasm and RER (intensive proteosynthesis)
synthesize IgE, which binds to antigens
usually in places where bacteria and foreign substances easily enter the body

Mast cells[edit | edit source]

large, ovoid shape
occur in the sparse collagen ligament of GIT and respiratory mucosa
mediate allergic reaction
1. receptors bind to IgE
2. basophilic secretory granules with histamine and heparin released
3. inflammation in surrounding tissue

Schematic comparison of wandering cells here.

Extracellular Component[edit | edit source]

Fibers[edit | edit source]

Collagen[edit | edit source]

Collagens include a family of proteins categorized into three main categories (fibril-forming, network forming, and anchoring). They are made up of individual fibrils of tropocollagen polymers. The thickness varies depending on the type.

The most well-known types and their locations are listed below. Mnemonic: Be So Totally Cool, Read Books!

collagen I (Bone, Skin, Tendons)
- ~1.5 nm diameter and 300 nm long
- most abundant
- 67 nm periodicity
collagen II (Cartilage - hyaline and elastic)
collagen III (Reticulin of reticular fibers)
collagen IV (Basal lamina)

Synthesis of collagen type I (most studied):

procollagen α chains produced by ribosomes in RER and imported into cisternae
Hydroxylases modify some AAs, requiring O₂, Fe²⁺, and Vitamin C
three α chains are aligned, linked by disulfides, and folded into a triple helix
triple helix is exocytosed, N- and C- terminal domains are cleaved off to form tropocollagen (basic subunit which is differently assembled into different types of collagen)
tropocollagen is converted to collagen molecules, which self-assemble into polymeric collagen (this is driven by entropy)
Lysyl oxidase cross-links collagen molecules to further stabilize structure

Schematic of synthesis here

Collagen is acidophilic and typically stains pink.

Elastic fibers[edit | edit source]

2 μm diameter elastic fibers
elastin gets embedded into fibrillin scaffolds to form elastic fibers
secreted by fibroblasts
found interspersed with collagen in locations subject to tensile or shear stress, as well as in elastic lamellae
allows structures to return to original shape

Reticular fibers[edit | edit source]

0.5-2 μm diameter
consist mostly of collagen type III
found in reticular connective tissue
- hematopoietic tissue (bone marrow and spleen)
- lymphatic tissue
- surrounds adipocytes, smooth muscle, nerve fibers, small blood vessels

Ground substance[edit | edit source]

Ground substance is a highly-hydrated space-filler between cells and in the ECM. It consists mainly of three different types of molecules

glycosaminoglycans (GAGs) aka mucopolysaccharides
- long polymers of repeating disaccharide units
- often sulfated
- ex: hyaluronic acid, chondroitinsulfate, keratansulfate
proteoglycans and their aggregates
- consist of a core protein with covalently bond sulfated GAGs (predominant part)
- e.g. aggrecan (in cartilage), perlecan (in basal lamina)
glycoproteins
- consist of a protein core with branched oligosaccharide chains
- e.g. fibronectin, laminin

Connective tissue proper[edit | edit source]

dominant fibrillar component, cells (mostly fibroblasts) rare
collagen fibers arranged to paralell or interlaced bundles
regular dense collagen c.t. (tendons)
irregular dense collagen c.t. (capsules of organs, sclera)


Connective Tissue Proper	Composition	Structure	Locations
Loose (areolar)	ground substance and many cells	randomly distributed fibers (much GAGs, elastic fibers, some collagen I&III)	stroma in epithelial organs, lamina propria of tunica mucosa, tela submucosa, tunica adventitia and organ interstitium
Dense regular	few cells (mostly fibroblasts), mostly collagen	parallel collagen fibers	ligaments, tendons, aponeuroses, stroma of cornea
Dense irregular	few cells (mostly fibroblasts), mostly collagen	randomly arranged collagen fibers	dermis, capsules of organs, sclera, GIT submucosa

Embryonic connective tissue[edit | edit source]

Mesenchyme[edit | edit source]

mostly a matrix of collagen fibers with undifferentiated cells (both components are sparse)
has progenitor cells for all adult connective tissue
found in embryonic mesoderm

Mucoid[edit | edit source]

originates from extra-embryonic mesoderm
random fibroblasts and collagen embedded in matrix of hyaluronic acid and GAGs (chondroitinsulfate)
ex: Wharton's jelly

Specialized connective tissue[edit | edit source]

Elastic connective tissue[edit | edit source]

high amount of elastic fibers arranged in parallel, with a few collagen fibers
sparse cells
ex: ligamenta flava of spine and other elastic ligaments, elastic membranes of arteries

Reticular connective tissue[edit | edit source]

reticular fibers produced by fibroblasts
provides supporting scaffold and attachment site for immune cells
found in bone marrow, secondary lymphatic organs, and some other tissues

Adipose tissue[edit | edit source]

Primarily made up of adipocytes (see above description)

Cartilage[edit | edit source]

Cartilage is a type of connective tissue that offers resistance yet is flexible and resilient.

The dominant constituent is ground substance, while collagen and elastic fibers are found in various proportions, depending on the type.

It is avascular, so nutrition has to be provided via diffusion from the synovial fluid or through the perichondrium.

The main cells are

chondroblasts
- actively synthesize cartilage matrix (ground substance, collagen and elastin)
- therefore, DNA is in euchromatin form, RER and Golgi app. are abundant
- cells group together in isogenous groups, chondrons, and territories
- spindle-shaped cells closer to perichondrium, spherical shape further away
chondrocytes
- decreased synthetic activity but function in maintenance

Elastic and hyaline cartilage are encapsulated by perichondrium, which is a layer of dense connective tissue. It has two layers:

fibrous layer
- contains dense irregular connective tissue with elastic fibers and fibroblasts
- functions in protection
- rich vascularization and innervation for chondrogenic layer below
chondrogenic layer
- hosts mesenchymal cells, which proliferate and differentiate to chondroblasts
- important in cartilage production

Classifications of cartilage[edit | edit source]

Schematic of the arrangement of cartilage cells and matrix in the individual types of cartilage can be found here.

Hyaline[edit | edit source]

consists of type II collagen and aggrecan
cells are alone or in isogenous groups, embedded within basophilic territorial matrix
can provide
- structural support (in fetal skeleton, ribs, respiratory tract)
- smooth surface for articulations

Scheme of the developing hyaline cartilage can be found here. Note the basophilic territorial matrix (due to a higher concentration of proteoglycans), while the interterritorial matrix is acidophilic

Elastic[edit | edit source]

consists of aggrecan and more noticeable fibrous component (type II collagen and elastic fibers)
cells are regularly dispersed
can provide
- structural support of soft tissues (epiglottis and small laryngeal cartilages)
- offer flexibility (external ear)

Fibrocartilage[edit | edit source]

consists mostly of type I collagen with some type II
isolated chondrocytes, also has fibroblasts
resistant to compression, shearing, and tension (intervertebral discs, menisci, pubic symphysis, tendon insertions)

Bone[edit | edit source]

Structure[edit | edit source]

Bone is a solid connective tissue composed of mineralized ECM.

periosteum: covers bone on outside
- outer component has dense irregular collagen
- inner component has osteoblasts and osteoprogenitor cells
- Sharpey’s (aka perforating) fibers fix it to the bone
endosteum: covers bone on inside (part that faces medullary cavity)
- thin layer of bone lining cells
- cells include osteoblasts, osteoprogenitor cell

Primary bone (woven, fibrilar)

scaffold of randomly oriented collagen fibers and dispersed bone cells
temporary structure
bone cells dispersed randomly
found in skull sutures, dental cement
otherwise replaced by secondary bone

Secondary bone (lamellar)

Consists of hydroxyapatite and collagen I fibrils (3-5 μm) highly oriented in similar direction
other proteins have structural or metabolic functions (ex. osteocalcin, osteonectin, osteopontin, bone sialoprotein)
trabecular (spongy) bone
- consist of trabecules (~300 μm) - interconnected rods and plates
- nutrients reach via diffusion from bone marrow
compact bone consists of
- Haversian systems (aka osteons, ~100-400 μm) of 5-20 bone lamellae concetrically arranged around vertical Haversian (aka central) canals
  - Haversian canals (~20 μm) are passages for capillaries or postcapillary venules and occasional c.t. and nerve fibers, lined by endosteum
  - transverse Volkmann canals (aka perforating canals) connect Haversian canals
- external and internal circumferential lamellae enclose the Haversian systems
- interstitial lamellae are between the Haversian systems

Schemes for bone structure are found here

Cells[edit | edit source]

osteoblasts
- derived from mesenchyme
- roughly cuboidal shape
- found on external and internal surface of bone
- synthesize organic components of matrix (osteoid) and collagen type I fibers
- therefore, have DNA in euchromatin form and abundant RER and Golgi apparatuses
- secrete osteocalcin protein, which binds Ca²⁺ (together with glycoproteins) and concentrates it, leading to mineralization
osteocytes
- derived from mesenchyme
- found enclosed in lacunae of mineralized bone matrix
- connected to each other and other bone cells via cytoplasmic processes through canaliculi ossium
- connections function as mechanosensors; stress elicits remedial responses from osteoblasts and osteoclasts
osteoclasts
- large, multi-nucleated cells (50-100 μm)
- derived from fusion of monocyte-macrophage progenitors; development requires polypeptides from osteoblasts
- found in in resorption lacunae (Howship’s lacunae) - enzymatically etched cavities
- part of the plasma membrane binds to the bone via a circular zone (sealing zone); the part that faces the subcellular pocket has many surface projections (ruffled border)
- osteoclasts pump protons and enzymes into the pocket to digest bone tissue

Schematics of principal ultrastructural hallmarks of osteoblasts, osteocytes and osteoclasts can be found here.

Joints[edit | edit source]

Bones join each other at joints. Joints can be classified according to the freedom of motion that they allow.

Diarthroses (synovial joints) allow free movement of the bones. An articular capsule encloses the joint and the synovial fluid within. The outer layer of the capsule consists of a fibrous layer. The synovium forms the inner layer of the articular capsule (as well as bursae and tendon sheaths). It is well-vascularized and innervated. It can be further divided into two layers: subintima, which consists of connective tissue, and intima, which has thin folds extending into the joint cavity and cuboidal cells with microvilli.

The synovial fluid itself is high in hyaluronans, serves in the exchange of gases, nutrients and wastes, and allows for the passage of leukocytes.

Synarthroses severely limit movement. These include fibrous joints (sutures, gomphoses) and cartilaginous synarthroses (synchondrosis).

Amphiarthroses allow limited movement. These include fibrous joints (syndesmoses) and cartilginous ones amphiarthroses (symphyses).

Bone ossification[edit | edit source]

There are two main types of ossification:

intramembraneous ossification
- direct ossification of mesenchyme precursor
- begins in ossification centers dispersed between network of developing capillaries
- osteoid is secreted by osteoblasts, calcifies, and forms woven bone
- eventually, ossification centers fuse with each other
- method of formation of flat bones
endochondral ossification
- ossification of hyaline cartilage model
- bone collar produced by osteoblasts prevents gas and nutrient exchange of underlying chondrocytes
- the underlying chondrocytes hypertrophy, compress matrix and initiate its calcification
- the hypertrophied chondrocytes die off, creating space for blood vessels
- more osteoprogenitor cells arrive and start forming woven bone
- method of forming most bones

Primary ossification centers form via endochondral ossification, and secondary ossification centers form in a similar way. Eventually, the woven bone is replaced by trabeculae or bone marrow. After the bones are ossified, the epiphyseal plate still remains and is responsible for growth.

Typical zonation of the epiphyseal plate (mnemonic: real people have career opportunities):

reserve zone (hyaline cartilage)
proliferating zone
hypertrophic (and maturation) cartilage
calcification (provisional) zone - has line of erosion
ossification and remodelling zone

Growth stops after puberty due to release of sex hormones. However, the timing varies for different bones, which allows one to determine age in clinical or forensical practice.

Schemes for bone ossification and zones of the growth plate are found here (see "Bone").

Bone remodelling[edit | edit source]

Bone remodelling is the continual process of renewing bone to adapt it to changing stress. Stress - disruption of the periosteum - attracts preosteoclasts, which mature and resorb bone in that region. This process is reversed by osteoblasts, which re-synthesize new bone. Since this process depends on signal pathways and regulators, disruption of the pathway can result in osteoporosis. Disruption of hormone levels (such as after menopause) or a lack of vitamin D are such examples that can lead to osteoporosis.

Scheme for bone remodelling here.

References[edit | edit source]

Mescher, A. and Junqueira, L., 2018. Junqueira's basic histology. New York: McGraw-Hill, pp. 96-159.

Vaňhara, Petr et al. Guide To General Histology And Microscopic Anatomy. 1st ed., Masaryk University Press, 2020, pp. 7-9.

@@ Line 1: / Line 1: @@
-{{Under construction}}
+== Components and Classification ==
+Connective tissue forms a matrix that supports and connects other tissues and organs. Below is an overview of its components:
-=='''CONNECTIVE  TISSUE'''==
+* Cells
-===Components of Connective Tissue===
+** Resident (fixed)
-Connective tissue it consist 3 types of components:
+** Transient (wandering)
+* ECM
+** Fibers
+** Amorphous ground substance
-''''''1) Cells of connective tissue'''''
+Connective tissue types belong to three main categories:
-:*Fibroblasts
-:*Adipocytes
+* Connective tissue proper
+** loose
+** dense irregular
+** dense regular
+* Embryonic connective tissue
+** mesenchyme
+** mucoid
+* Specialized connective tissue
+** reticular
+** adipose
+**elastic
+** cartilage
+** bone
+** blood
-:*Macrophage and Mononuclear Phagocyte System
+== Types of the cells of connective tissue ==
-:*Mast Cells
+=== Fixed cells ===
+Reside within connective tissue. Derived from mesenchyme.
-:*Plasma Cells
+==== Fibroblasts ====
+Fibroblasts function in synthesis and degradation of the ECM. Therefore, DNA is in euchromatin form, and the RER and Golgi apparatuses are abundant. Fibro''cytes'' are "retired" fibroblasts that do not synthesize much.
-:*Leucocytes
+==== Reticular cells ====
+Similar to fibroblasts, produce reticular fibers. N<small>ote: Reticular cells ≠ reti</small>culocytes! Reticulocytes are immature RBCs.
-'''2)	Fibers of connective tissus'''
+==== Adipocytes ====
-:*Collagen
+* '''Univacuolar'''
+** spherical cell
+** one large vacuole (stores triacylglycerols) takes up most of the space
+** cytoplasm, flattened nucleus and other organelles are pushed to the periphery of the cell
+** major component of <u>white</u> adipose tissue
+*** energy storage
+*** also functions in hormone production (adipokinins, leptins)
+*** highly vascularized
+* '''Multivacuolar'''
+** multiple smaller fat droplets
+** nucleus is more central
+** burns fat to heat via mitochondria, functions in thermoregulation
+** major component of <u>brown</u> adipose tissue
+*** more abundant in fetuses, neonates and small children
+*** found primarily between scapulae, in axilla, mediastinum, and retroperitoneum
-:*Reticular fibers
+==== Pigment (melanin) cells ====
-:*Elastic fibers
+* irregularly shaped
+* arise from ''neuroectoderm'' rather than mesenchyme
+* synthesize and store melanin
-'''3)Ground substances of connective tissue'''
+Schematic comparison of all fixed cells [[wikiskripta:Soubor:Buňky_fixní.jpg|here]].
-Connective tissue is mostly consisted by ECM=Extracellular matrix and  not from cells like other tissues.
+=== Wandering cells ===
-Extracellular matrix consists of :
+Formed in red bone marrow from hemocytoblasts, enter connective tissue via bloodstream.
-:*protein fibers
-:*collagen
-:*reticular fibers
-:*elastic fibers
-:*ground substance
-:*anionic macromolecules:
-:::•	glycos-aminoglycans
-:::•	proteo-glycans
-:*multi adhesive glycoproteins:
-:::•	laminin
-:::•	fibronectin  (That stabilizes the ECM by binding to the receptor proteins  integrins on the surface of cells)
-===Role:===
+==== Macrophages ====
--	structural
--      biological= a reservoir of factors that controls the growth and the differentiation
--	Medium in which nutrients and metabolic wastes are exchange between cells and their blood supply ( due  to its hydrated nature)
-===Origin:===
+* variable shape with protrusions
+* kidney-shaped nucleus
+* phagocytose debris, damaged, or foreign cells
+* mainly in sparse connective tissue along capillaries
-Mesenchyme (Mesenchymal cells)
+==== Plasma cells ====
--	develops from the mesoderm (middle layer of the embryo)
--	migrate from their site of origin surrounding all developing organs
+* eccentrically placed nucleus, alternating heterochromatin and euchromatin
+* large amount of cytoplasm and RER (intensive proteosynthesis)
+* synthesize IgE, which binds to antigens
+* usually in places where bacteria and foreign substances easily enter the body
--	develops into other types of structure such as:
+==== Mast cells ====
-:* blood cells
+* large, ovoid shape
-:* endothelial cells
+* occur in the sparse collagen ligament of GIT and respiratory mucosa
-:* muscle cells
+* mediate allergic reaction
+*# receptors bind to IgE
+*# basophilic secretory granules with histamine and heparin released
+*# inflammation in surrounding tissue
-=='''CELLS OF CONNECTIVE TISSUE'''==
+Schematic comparison of wandering cells [[wikiskripta:Soubor:Bloudivé_buňky.jpg|here]].
-The connective tissue is consisted of many different cells with different origin and different function as:
+== Extracellular Component ==
-==='''Fibroblasts'''===
+=== Fibers ===
--Fibroblasts originate from Mesenchymal cells ,are the most common cells in connective tissue, and spend all their life to connective tissue.
--Synthesize:
+==== Collagen ====
+Collagens include a family of proteins categorized into three main categories (fibril-forming, network forming, and anchoring). They are made up of individual fibrils of tropocollagen polymers. The thickness varies depending on the type.
-:* collagen
+The most well-known types and their locations are listed below. Mnemonic: '''B'''e '''S'''o '''T'''otally '''C'''ool, '''R'''ead '''B'''ooks!
-:* elastin
+* '''collagen I''' ('''B'''one, '''S'''kin''', T'''endons)
+** ~1.5 nm diameter and 300 nm long
+** most abundant
+** 67 nm periodicity
+* '''collagen II''' ('''C'''artilage - hyaline and elastic)
+* '''collagen III''' ('''R'''eticulin of reticular fibers)
+* '''collagen IV''' ('''B'''asal lamina)
-:* glycos-aminoglycans
+Synthesis of collagen type I (most studied):
-:* proteo-glycans
+# '''procollagen α''' chains produced by ribosomes in RER and imported into cisternae
+# Hydroxylases modify some AAs, requiring O<sub>2</sub>, Fe<sup>2+</sup>, and <u>Vitamin C</u>
+# three α chains are aligned, linked by disulfides, and folded into a '''triple helix'''
+# triple helix is exocytosed, N- and C- terminal domains are cleaved off to form '''tropocollagen''' (basic subunit which is differently assembled into different types of collagen)
+# tropocollagen is converted to collagen molecules, which self-assemble into polymeric collagen (this is driven by entropy)
+# Lysyl oxidase cross-links collagen molecules to further stabilize structure
-:* multi-adhesive glycoproteins
--Have two stage of activity and they can be differentiated microscopically:
+Schematic of synthesis [https://upload.medbullets.com/topic/102078/images/collagen.jpg here]
-* '''fibroblast = active cell'''
+Collagen is acidophilic and typically stains pink.
-::-	large cell
+==== Elastic fibers ====
-::-	ovoid, large, pale-stain  nuclei with fine chromatin,
-::-	prominent nucleolus
-::-	Basophilic, abundant, irregular cytoplasm,
-::-	rich in rough ER,
-::-	and well developed App. Golgi
-* '''fibrocyte  = dormant cell'''
+* 2 μm diameter elastic fibers
+*elastin gets embedded into fibrillin scaffolds to form elastic fibers
+* secreted by <u>fibroblasts</u>
+* found interspersed with collagen in locations subject to tensile or shear stress, as well as in elastic lamellae
+* allows structures to return to original shape
-::-	small cell
+==== Reticular fibers ====
-::-	smaller and heterochromatic , darker , elongated nuclei,
-::-	more acidophilic cytoplasm with less RER
-::-Are targets of various growth factors that influence growth and differentiation!
+* 0.5-2 μm diameter
+* consist mostly of collagen type III
+* found in reticular connective tissue
+** hematopoietic tissue (bone marrow and spleen)
+** lymphatic tissue
+** surrounds adipocytes, smooth muscle, nerve fibers, small blood vessels
-====Medical application:====
+=== Ground substance ===
+Ground substance is a highly-hydrated space-filler between cells and in the ECM. It consists mainly of three different types of molecules
-The regenerative capacity of connective tissue  is responsible for repairing destroyed tissues:
+* '''glycosaminoglycans''' (GAGs) aka mucopolysaccharides
+** long polymers of repeating disaccharide units
+** often sulfated
+** ex: <u>hyaluronic acid</u>, chondroitinsulfate, keratansulfate
+* '''proteoglycans''' and their aggregates
+** consist of a core protein with covalently bond sulfated GAGs (predominant part)
+** e.g. aggrecan (in cartilage), perlecan (in basal lamina)
+* '''glycoproteins'''
+** consist of a protein core with branched oligosaccharide chains
+** e.g. fibronectin, <u>laminin</u>
-'''Scar''' is formed by connective tissue (CT) after traumatic or inflammation injury.
+== Connective tissue proper ==
-'''Healing of surgical incisions''' depends on reparative capacity of Connective T:
+* dominant fibrillar component, cells (mostly fibroblasts) rare
+* collagen fibers arranged to paralell or interlaced bundles
+* regular dense collagen c.t. (tendons)
+* irregular dense collagen c.t. (capsules of organs, sclera)
-::* The fibrocyte reverts to the fibroblast state
+{| class="wikitable"
+|+
+!Connective Tissue Proper
+!Composition
+!Structure
+!Locations
+|-
+|Loose (areolar)
+|ground substance and many cells
+|randomly distributed fibers (much GAGs, elastic fibers, some collagen I&III)
+|stroma in epithelial organs, lamina propria of tunica mucosa, tela submucosa, tunica adventitia and organ interstitium
+|-
+|Dense regular
+| rowspan="2" |few cells (mostly fibroblasts), mostly collagen
+|parallel collagen fibers
+|ligaments, tendons, aponeuroses, stroma of cornea
+|-
+|Dense irregular
+|randomly arranged collagen fibers
+|dermis, capsules of organs, sclera, GIT submucosa
+|}
-::* The myofibroblast, a cell with features of both fibroblast and smooth muscle cell plays a basal role in''' “wound contraction”.'''
+== Embryonic connective tissue ==
-::* Myofibroblasts  have most of the morphological characteristics of  fibroblasts but contain a big quantity of  Actin microfilaments and myosin responsible for the wound healing
+=== Mesenchyme ===
+* mostly a matrix of collagen fibers with undifferentiated cells (both components are sparse)
+* has progenitor cells for all adult connective tissue
+* found in embryonic mesoderm
-==='''Adipocytes'''===
+=== Mucoid ===
--They are connective tissue cells, special storage of neutral fats and the producers of heat. They are called''' fat cells'''.
-=== Macrophages and mononuclear phagocyte system'''===
+* originates from extra-embryonic mesoderm
--Originate from hematopoietic stem cell in bone marrow, circulate in the blood and after move into connective tissue where remain and execute their function
+* random fibroblasts and collagen embedded in matrix of hyaluronic acid and GAGs (chondroitinsulfate)
--They have different morphology, different name and different function in base of their location in specialized tissue:
+* ex: Wharton's jelly
-*'''in connective tissue = Macrophages '''.
-:*  '''defense cells'''and produce chemotactic factors, cytokines and several enzymes. In case of inflammation macrophages are stimulated and are arranged in clusters forming epithelioid cells (they look like epithelial cells). Change their morphological characteristics and metabolism becoming activated with increase capacity of phagocytosis.
-: * ''' antigen-presenting cells'''. They have class II MHC molecules in their surface. The CD4 Helper lymphocytes are activated by the presentation of antigen on Class II MCH molecule and proliferate by mitosis. The daughter T-cell lymphocytes activate the B cells that also proliferate by mitosis and after that differentiate into plasma cells. These plasma cells secrete specific antibodies for the antigen presented.
-*'''in blood=monocytes'''.  They  are precursors of macrophages. Usually are increasing in viral infections.
-*'''in Liver=Kuppfer cells'''  They are macrophages.
-* '''in nerve tissue and central nervous system=Microglia cell'''. They are Macrophages.
-*'''in Lymph nodes=Dendritic cells'''. They are Antigen presenting cells and are important in immune respond
-*'''in Skin=Langerhans cells'''.They are Antigen presenting cells.
-==='''Mast cells'''===
+== Specialized connective tissue ==
-Masts cells originate from '''Hematopoietic stem cell,''' the progenitor cell in Bone marrow. This progenitor circulates in blood, cross the wall of venules and capillaries and they penetrate the connective tissue where they proliferate and differentiate. They are not found in blood. They are large oval or round connective tissue cells. Their cytoplasm is filled with basophilic secretory granules containing paracrine compounds that promote local inflammatory response as:
-:* histamine – acts in allergic reaction.
-:* heparine –acts locally as anticoagulant
-:* serine proteases- activate various mediators of inflammation
-:* eosinophil and neutrophil chemotactic factors. In special conditions as in anaphylactic reactions Eosinophil chemotactic factor attracts eosinophils in phase of allergic reaction.
-:* leucotrienes C4, D4, SRS-A=Slow Reacting Substance of Anaphylaxis
-The granules display metachromasia=they can change color of some basic dyes (ex.toluidine blue) from blue to purple or red. This happens due to the high content of acidic radicals in their glycosaminoglycans and they are poorly preserved by common fixatives (usually mast cells are difficult to identify).
-The small, central, spherical nucleus is usually obscured by the cytoplasmic granules
-Specific locations of masts cells:
--'''Perivascular masts cells''' are near small blood vessels in skin and mesenteries.
--'''Mucosal mast cells''' in mucosa lining in digestive tract and in respiratory tract
-====Medical application====
+=== Elastic connective tissue ===
-'''Anaphylactic shock''' is an immediate hypersensitive reaction.
-It occurs very quickly, within a few minutes, after penetration by an antigen of an individual previously sensitized. When the allergen (antigen) enters for the first time in the organism , plasma cell produce a specific IgE ( immunoglobulin or antibody contra the specific allergen) that is bound to the surface of a Mast cell. When a second exposure to the same antigen occurs, these are bind to IgE on mast cell which is activated leading to degranulation. Liberated histamine causes contraction of smooth muscle mainly in the bronchioles, and dilates and increases the permeability of capillaries. Due to the action of histamine are the symptoms of dyspnea and blushing that appear in this condition. The Eosinophil Chemotactic Factor of Anaphylaxis attracts blood Eosinophils. So in this condition in the full blood count characteristically appears eosinophilia (absolute number of eosinophils more than 800). Due to the fact that mast cells are abundant in skin, respiratory and digestive system the mainly symptoms in anaphylactic shock are concentrated initially at these areas.
-==='''Plasma Cell'''===
+* high amount of elastic fibers arranged in parallel, with a few collagen fibers
+* sparse cells
+* ex: ligamenta flava of spine and other elastic ligaments, elastic membranes of arteries
-'''Morphology'''
+=== Reticular connective tissue ===
-*Are large ovoid cells
-*With basophilic cytoplasm due to rich RER
-*eccentrically placed, not central nucleus
-*Nucleus is  spherical with an appearance of «clock-face»
-*Juxtanuclear Golgi apparatus + centriole ( pale region of the cell)
-*Normal there are a few plasma cell in most connective tissue.
-*Their life spasm is only 10-20 days.
-===='''Medical application'''====
+* reticular fibers produced by fibroblasts
-* '''Immune respond to an antigen'''. Plasma cells  are derived from B Lymphocytes and are responsible for synthesis of imunoglobulins. These are the antibodies that are produced after the penetration of a bacterium or (in general) an antigen the organism. Each antibody is specific for each antigen.
+* provides supporting scaffold and attachment site for immune cells
-* '''Malignant transformation''' of plasma cells leads to Monoclonal Plasma cells. These are cells that secrete a monoclonal immunoglobulin. When these monoclonal plasma cells represent  more than 30% of the total bone marrow cells  produce the hematological disease named Multiple myeloma with characteristic bone lytic lesions.
+* found in bone marrow, secondary lymphatic organs, and some other tissues
-===	Leucocytes ===
+=== Adipose tissue ===
-Originate from hematopoietic stem cell in the bone marrow, move to the connective tissue where they reside for a few days. They are transient cells of most connective tissue and usually die by apoptosis. Leukocytes migrate from the blood vessels by diapedesis. Diapedesis is increased during inflammation (defensive reaction against foreign substances or bacteria). Sings for inflammation are redness, swelling, heat and pain. Leucocytes do not return to the blood after arriving in connective tissue except lymphocytes.
+Primarily made up of adipocytes (see above description)
-==''' FIBERS OF CONNECTIVE TISSUE'''==
+=== Cartilage ===
+Cartilage is a type of connective tissue that offers resistance yet is flexible and [https://en.wikipedia.org/wiki/Resilience_(materials_science) resilient].
-==='''Collagen'''===
+The dominant constituent is ground substance, while collagen and elastic fibers are found in various proportions, depending on the type.
--It is a family of proteins!
+It is avascular, so nutrition has to be provided via diffusion from the synovial fluid or through the perichondrium.
--The most abundant protein in human body (30% of the body weight)
+The main cells are
--We have more than 20 types of collagen in function of the degree of rigidity, elasticity and strength the cell type  (which produce the collagen), the molecular composition, the morphological characteristics, function and distribution.
+* '''chondroblasts'''
+** actively synthesize cartilage matrix (ground substance, collagen and elastin)
+** therefore, DNA is in euchromatin form, RER and Golgi app. are abundant
+** cells group together in isogenous groups, chondrons, and territories
+** spindle-shaped cells closer to perichondrium, spherical shape further away
+* '''chondrocytes'''
+** decreased synthetic activity but function in maintenance
-====''' Classification''' ====
+Elastic and hyaline cartilage are encapsulated by '''perichondrium''', which is a layer of dense connective tissue. It has two layers:
-'''According to their structure + Function are classified in 4 categories:'''
-'''1)	COLLAGEN that form FIBLILS (Visible by optical microscopy)'''
+* fibrous layer
+** contains dense irregular connective tissue with elastic fibers and fibroblasts
+** functions in protection
+** rich vascularization and innervation for chondrogenic layer below
+* chondrogenic layer
+** hosts mesenchymal cells, which proliferate and differentiate to chondroblasts
+** important in cartilage production
-*Type I	    -Skin, Tendon, Bone, dentin        -Resistance to tension
+==== Classifications of cartilage ====
+Schematic of the arrangement of cartilage cells and matrix in the individual types of cartilage can be found [http://histologie.lfp.cuni.cz/education/Web_histo_schemata/eng/chon/imgs/cartilago1.jpg here].
-*Type II        -Cartilage, vitreous body	         -Resistance to pressure
+===== Hyaline =====
-*Type III       -Skin, muscle, blood vessels        -Structural maintenance in expansible organs
+* consists of type II collagen and aggrecan
+* cells are alone or in isogenous groups, embedded within basophilic territorial matrix
+* can provide
+** structural support (in fetal skeleton, ribs, respiratory tract)
+** smooth surface for articulations
-*Type V         -Fetal tissues, Skin, bone          - Participate in type I  Collagen function
+Scheme of the developing hyaline cartilage can be found [http://histologie.lfp.cuni.cz/education/Web_histo_schemata/eng/chon/imgs/cartilago2.jpg here]. Note the basophilic territorial matrix (due to a higher concentration of proteoglycans), while the interterritorial matrix is acidophilic
-*Type XI        - Cartilage	                	 - Participate in type II  Collagen function
+===== Elastic =====
-The molecules of this collagen:
+* consists of aggrecan and more noticeable fibrous component (type II collagen and elastic fibers)
+* cells are regularly dispersed
+* can provide
+** structural support of soft tissues (epiglottis and small laryngeal cartilages)
+** offer flexibility (external ear)
-:*aggregate to form fibrils clearly visible in optical microscopy
+===== Fibrocartilage =====
-:*collagen type I is the most abundant in organism
+* consists mostly of type I collagen with some type II
+* isolated chondrocytes, also has fibroblasts
+* resistant to compression, shearing, and tension (intervertebral discs, menisci, pubic symphysis, tendon insertions)
-:*make the structures of the tissues named '''“ collagen fibers”''' forming tendons, organ capsules and dermis
+=== Bone ===
+==== Structure ====
+Bone is a solid connective tissue composed of mineralized ECM.
-'''2)	FIBRIL associated COLLAGENS ( Not visible detected by immunochemistry)'''
+* '''periosteum''': covers bone on outside
+** outer component has dense irregular collagen
+**inner component has osteoblasts and osteoprogenitor cells
+** Sharpey’s (aka perforating) fibers fix it to the bone
+* '''endosteum''': covers bone on inside (part that faces medullary cavity)
+** thin layer of bone lining cells
+** cells include osteoblasts, osteoprogenitor cell
-*Type IX    - Cartilage, vitreous body      -Bound glycos-aminoglicans and is associated with Collagen type II
+'''Primary bone''' '''(woven, fibrilar)'''
-*Type XII   - Embryonic tendon, Skin      -Interacts with type II collagen
+* scaffold of randomly oriented collagen fibers and dispersed bone cells
+*temporary structure
+* bone cells dispersed randomly
+* found in skull sutures, dental cement
+*otherwise replaced by secondary bone
-*Type XIV-Fetal skin, tendon
+'''Secondary bone (lamellar)'''
-These types of collagens:
-:*Are short structures
+* Consists of hydroxyapatite and collagen I fibrils (3-5 μm) highly oriented in similar direction
+* other proteins have structural or metabolic functions (ex. osteocalcin, osteonectin, osteopontin, bone sialoprotein)
+*'''trabecular (spongy) bone'''
+** consist of trabecules (~300 μm) - interconnected rods and plates
+** nutrients reach via diffusion from bone marrow
+* '''compact bone''' consists of
+** Haversian systems (aka osteons, ~100-400 μm) of 5-20 bone lamellae concetrically arranged around vertical Haversian (aka central) canals
+*** Haversian canals (~20 μm) are passages for capillaries or postcapillary venules and occasional c.t. and nerve fibers, lined by endosteum
+*** transverse Volkmann canals (aka perforating canals) connect Haversian canals
+** external and internal circumferential lamellae enclose the Haversian systems
+** interstitial lamellae are between the Haversian systems
-:*That binds the surface of collagen fibrils to one another and to other component of the ECM
+Schemes for bone structure are found [http://histologie.lfp.cuni.cz/education/Web_histo_schemata/eng/index_en.html here]
-:*Are also known as''' FACIT: Fibril Associated Collagens with Interrupted Triple helices'''
+===== Cells =====
+* '''osteoblasts'''
+** derived from mesenchyme
+**roughly cuboidal shape
+**found on external and internal surface of bone
+** synthesize organic components of matrix (osteoid) and collagen type I fibers
+**therefore, have DNA in euchromatin form and abundant RER and Golgi apparatuses
+** secrete <u>osteocalcin</u> protein, which binds Ca<sup>2+</sup> (together with glycoproteins) and concentrates it, leading to mineralization
+* '''osteocytes'''
+** derived from mesenchyme
+**found enclosed in lacunae of mineralized bone matrix
+** connected to each other and other bone cells via cytoplasmic processes through canaliculi ossium
+** connections function as mechanosensors; stress elicits remedial responses from osteoblasts and osteoclasts
+* '''osteoclasts'''
+** large, multi-nucleated cells (50-100 μm)
+**derived from fusion of monocyte-macrophage progenitors; development requires polypeptides from osteoblasts
+**found in in resorption lacunae (Howship’s lacunae) - enzymatically etched cavities
+** part of the plasma membrane binds to the bone via a circular zone (sealing zone); the part that faces the subcellular pocket has many surface projections (ruffled border)
+** osteoclasts pump protons and enzymes into the pocket to digest bone tissue
-'''3)	COLLAGEN that forms ANCHORING FIBRILS ( not visible detected by immunochemistry)'''
+Schematics of principal ultrastructural hallmarks of osteoblasts, osteocytes and osteoclasts can be found [https://www.histology.leeds.ac.uk/bone/bone_cell_types.php here].
-*Type VII  -Epithelia	 -Anchors skin, epidermal basal lamina to underlying stroma
+==== Joints ====
+Bones join each other at joints. Joints can be classified according to the freedom of motion that they allow.
-This type of collagen:
-:*Bind the basal lamina to reticular fibers in the underlying connective tissue
+'''Diarthroses'''  (synovial joints) allow free movement of the bones. An articular capsule encloses the joint and the synovial fluid within. The outer layer of the capsule consists of a fibrous layer. The '''synovium''' forms the inner layer of the articular capsule (as well as bursae and tendon sheaths). It is well-vascularized and innervated. It can be further divided into two layers: ''subintima,'' which consists of connective tissue, and ''intima'', which has thin folds extending into the joint cavity and cuboidal cells with microvilli.
+The '''synovial fluid''' itself is high in hyaluronans, serves in the exchange of gases, nutrients and wastes, and allows for the passage of leukocytes.
-'''4)	COLLAGEN that forms NETWORKS (not visible detected by immunochemistry)'''
+'''Synarthroses''' severely limit movement. These include fibrous joints (sutures, gomphoses) and cartilaginous synarthroses (synchondrosis).
-*Type IV  – All basement membranes     - Support of delicate structures and - Filtration
+'''Amphiarthroses''' allow limited movement. These include fibrous joints (syndesmoses) and cartilginous ones amphiarthroses (symphyses).
-This type of collagen *constitutes the major structural component of basal lamina
+==== Bone ossification ====
+There are two main types of ossification:
-===='''Synthesis'''====
+* '''intramembraneous ossification'''
-Collagen synthesis can be done in different cells as fibroblast, chondroblast, osteoblast and odontoblast.
+** direct ossification of mesenchyme precursor
-*In ribosome on RER is produced the procollagen '''“a chain”'''
+**begins in ossification centers dispersed between network of developing capillaries
-* This is intertwine (πλέκεται) to make triple helices and held together by hydrogen bonds and hydrophobic interactions
+**osteoid is secreted by osteoblasts, calcifies, and forms woven bone
-*Every third amino-acid in “a chain” is''' glycine'''
+**eventually, ossification centers fuse with each other
-*Two other small amino-acids abundant in collagen are hydroxylated and form '''hydroxyproline''' and '''hydroxylysine.'''
+**method of formation of flat bones
-*The 3 “a chain” forms a '''rod-like procollagen molecule''' and can be:
+* '''endochondral ossification'''
-:'''-homotrimetric'''  = when the 3 “a chain” are  identical
+** ossification of hyaline cartilage model
-:'''-heterotrimetric''' = when the 2 or all 3 “a chains” different
+**bone collar produced by osteoblasts prevents gas and nutrient exchange of underlying chondrocytes
+**the underlying chondrocytes hypertrophy, compress matrix and initiate its calcification
+**the hypertrophied chondrocytes die off, creating space for blood vessels
+**more osteoprogenitor cells arrive and start forming woven bone
+**method of forming most bones
-*In collagen I, II and III the procollagen molecules are aggregate and become packed together forming '''FIBRILS'''
+Primary ossification centers form via endochondral ossification, and secondary ossification centers form in a similar way. Eventually, the woven bone is replaced by trabeculae or bone marrow. After the bones are ossified, the epiphyseal plate still remains and is responsible for growth.
-'''Collagen fibrils:'''
-*are thin, elongated structures with diameter =20-90 nm
-*have transverse striations with periodicity (64-68nm)
-*this is caused by the regular overlapping arrangement of the collagen molecules
--In some collagen types (V, XI) fibrils associate further with''' FACIT''' collagen to form''' FIBERS'''
+Typical zonation of the '''epiphyseal plate''' (mnemonic: real people have career opportunities):
+* reserve zone (hyaline cartilage)
+* proliferating zone
+* hypertrophic (and maturation) cartilage
+* calcification (provisional) zone - has line of erosion
+* ossification and remodelling zone
+Growth stops after puberty due to release of sex hormones. However, the timing varies for different bones, which allows one to determine age in clinical or forensical practice.
--In collagen type I the fibers can form large '''BUNDLES'''
+Schemes for bone ossification and zones of the growth plate are found [http://histologie.lfp.cuni.cz/education/Web_histo_schemata/eng/index_en.html here] (see "Bone").
--In collagen type II (present in cartilage) the fibrils '''does NOT''' form fibers or bundles
+==== Bone remodelling ====
+Bone remodelling is the continual process of renewing bone to adapt it to changing stress. Stress - disruption of the periosteum - attracts preosteoclasts, which mature and resorb bone in that region. This process is reversed by osteoblasts, which re-synthesize new bone. Since this process depends on signal pathways and regulators, disruption of the pathway can result in osteoporosis. Disruption of hormone levels (such as after menopause) or a lack of vitamin D are such examples that can lead to osteoporosis.
--Collagen type IV (present in all membranes) assembles as a '''lattice-like network''' in the basal lamina
+Scheme for bone remodelling [https://www.orthopaedicsone.com/download/attachments/71434800/bone+remodel.png?version=1&modificationDate=1389455440000 here].
+== References ==
+Mescher, A. and Junqueira, L., 2018. ''Junqueira's basic histology''. New York: McGraw-Hill, pp. 96-159.
-Microscopic examination:
+Vaňhara, Petr et al. ''Guide To General Histology And Microscopic Anatomy''. 1st ed., Masaryk University Press, 2020, pp. 7-9.
--In spite of «the fresh collagen fibers» are colorless strands, when appears in increased numbers for ex. In tendons, they appear''' white'''
+__INDEX__
--In the light microscope collagen fibers are acidophilic and they stain:
-*'''Pink''' with Eosin
-*'''bleu''' with Malory trichrome stain
-*'''green''' with Masson trichrome stain
-*'''red''' with Sirius red
+[[Category:Histology]]
-===='''Medical application'''====
-*'''Osteogenesis Imperfecta'''= A mutation in a single amino acid for example in glycine in colagen type I. Patients show spontaneous fractures and cardiac insufficiency
-*'''Progressive systemic sclerosis'''= over accumulation of collagen (fibrosis).
-*'''keloid'''= local swelling in the place of scars of the skin
-*'''Scurvy'''= Deficiency of Vit C is characterized by degeneration of connective tissue. In Vit C deficiency the fibroblasts synthetize defective collagen (In the hydroxylation of prolyne) Symptoms are loss of teeth and bleedings. Treatment by fresh food, particularly citrus fruit rich in vitamin C.
-==='''Reticular fibers'''===
-Reticular fibers are consisted mainly by collagen type III and forms thin and extensive network around the parenchymal cells of various organs for example liver and endocrine gland and in Hematopoietic organs  for example spleen, lymph nodes, red bone marrow.
-They are NOT visible in H&E heamtoxyline& Eosin preparation. They are stained BLACK by '''silver salts''' and are also called '''argyrophilic'''. They are also '''PAS positive'''.
-==='''Elastic Fibers'''===
-Elastic fibers re thinner than the average collagen fiber, form sparse networks interspersed with collagen bundles in many organs as the wall of large arteries. he major functional property is to give elasticity to the organs.
-Developing of E.F is made in 3 stages:
-'''1)	First stage:'''
-*Fibrillin: a large glycoprotein  formed from a core of 10-nm microfibrils
-*Fibrillin binds Elastin = forms scaffolding (σύστημα σκαλωσιάς) necessary for deposition of elastin
-*Microfibrils and fibrillin alone are used in some organs such as to hold in place the lens of the eye.  Such Microfibrils are not elastic but are highly resistant to
-pulling forces
-:* Defective fibrillin = leads to th eproduction of fragmented elastic fibrils
-'''2)	Second Stage:'''
-*deposition of elastin between microfibrils forming larger fibers
-*Elastin molecules:
-:-are globular and
-:-are secreted by '''fibroblasts''' in connective tissue and by  '''smooth muscle cells''' in walls of blood vessels
-:-are rich in '''glycine''' and '''prolyne''' with many regions
-:-polymerize to form fibers or sheet-like structures
-:-contains 2 amino acids '''desmosine''' and '''isodesmosine''' which are produced when '''cross-links''' are formed among '''4 lysine residues''' in different elastic molecules
-:-cross-links formed in lysine residues are catalyzed by '''lysil oxidase'''
-:-is resistant to digestion by most proteases
-:-is easily hydrolyzed by  '''pancreatic elastase'''
-'''3)	Third stage:'''
-Mature elastic fibers is produces by accumulation of elastin, which further surrounded by a thin sheath of microfilaments
-* '''Elastic lamellae'''= in the wall of large blood vessels, elastin occurs as a '''fenestrated sheet''' named elastic lamellae or elastic sheet
-* '''Microfibrils of fibrillin''' in some organs are used alone as in''' eye''' to hold in place the lens
-'''Microscopic examination'''
-Elastic fibers is difficult to be demonstrated by H&E.They are demonstrated with '''Aldehyde Fuscin''' which stains elastin a''' dark magenta'''
-===='''Medical application'''====
-'''Syndrom Marfan:''' mutation in the fibrillin gene, the protein that produce the scaffolding necessary for elastin. Patient with Syndrome Marfan
-is tall and thin. His tissues are not resistant (lack of the resistance in tissue rich in elastic fibers) and his big vessels like aorta usually have aneurysm that is very dangerous to be dissected.
-=='''GROUND SUBSTANCES'''==
-The ground Substance of ECM is a complex mixture of macromolecules glycos-aminoglycans (GAGs), proteo-glycans and multi adhesive glycoproteins. This transparent mixture fills the space between cells and fibers and acts as lubricant and barrier to the penetration of invaders
-==='''Glycos-aminoglycans (GAGs)'''===
-The GAGs originally called mucopolysacharides and formed from repeating disaccharide units composed from:
-- Hexozamine + Urotic acid
-:'''Hyaluronic acid''' is the most ubiquitous GAG with a molecular weight from 100-1000KDa
-Is a long polymer of a disaccharide glucosamine-glucuronate and is synthesized directly into ECM by the enzyme hyaluronate synthetase located in the membrane of many cells.This binds a big amount of water giving it a role in diffusion of molecules in connective tissue and in lubricating various organs and joints.is found in umbilical cord, synovial fluid, vitreous humor, and cartilage.
-:'''All other GAGs''' are much smaller 10-40kDa and they are attached to proteins (Proteo-glycans). They are rich in sulfate and are intense hydrophilic and viscous.
-==='''Proteo-glycans ''' ===
-Proteoglycans are composed of a core protein + GAG/s, are synthetized on RER, mature in Golgi and secreted from cells by exocytosis
-The main differences between Proteoglicans and Glycoproteins are:
-* Proteoglycans:
-:-Contain a core protein as a vertical rod
-:-GAGs are covalently bound
-:-GASs are unbranched polysaccharide
-:-Contain a greater amount of carbohydrate (Than glycoproteins)
-:-Can be pictured as a “test tube brush”
-* Glycoproteins:
-:-Are globular protein molecule
-:-Chains of monosaccharides are covalently attached
-:-Polypeptide content is greater than polysaccharide content
-Proteoglycans are distinguished for their diversity and are proteoglycans of :
-:* Extracellular Matrix (ECM) . Best example is '''Aggrecan''' :
--is one of the most important ECM proteoglycans
--Is the dominant proteoglycan in cartilage
--The core protein has several chondroitin sulfate and keratin sulfate chains
-- And is bound via a link protein to hyaluronic acid
-:* Cell Surface. Best example is '''Syndecan'''.
--Is a cell surface proteoglycan
--Is present on many types of cells , particularly epithelial cells
--The core protein spans the plasma membrane with a short cytoplasmic extension ->Heparan sulfate chains are attached to the extracellular extension
-==='''Multiadhesive glycoproteins'''===
-Multiadhesive glycoproteins have attached carbohydrates that are usually branched	.The protein component predominates
--'''ROLE:''' in adhesion of cells to their substrate
-'''1) Fibronectin'''
-*Is synthetized by fibroblasts  and epithelial cells
-*Is a dimeric molecule with binding sites for
-:::-Collagens
-:::-GAGs
-:::-Integrins of cell membranes
-*For this reason is named Multiadhesive glycoprotein
-*All these interactions lead to normal''' Cell Adhesion''' and''' migration'''
-*Fibronection is as a '''network''' in the intercellular spaces of many tissues
-'''2) Laminin'''
-*is a trimetric cross-shaped glycoprotein with binding sites for
-:::-Collagen type IV
-:::-GADs
-:::-Integrins
-*participate in adhesion of '''epithelium cells to basal lamina'''
-'''3) Integrins = Matrix receptor'''
-*Are cell-surface molecule that bind to
-:::-Collagen
-:::-Fibronectin
-:::-Laminin
-*Are '''transmembrane receptors ''' or  linker proteins and
-*Interact also with cytoskeleton ''' Actin microfilaments'''  in the presence of '''Talin''' and '''Vinculin'''
-* These receptor connect the components of ECM (collagen, Fibronectin, Laminin) with the intracellular components (actin via Talin)
-'''Interstitial fluid'''
--In connective tissue there is a small quantity of free fluid
--Is similar to blood plasma
--Contains a small quantity of plasma proteins of low molecular that pass through the cappillay walls due to hydrostatic pressure of the blood
--Contains almost the 30% of   total plasma proteins of the body
-===='''Medical application'''====
-'''Edema:''' Is the accumulation of water in the extracellular spaces and is possible to be produced in:
-*Venous or lymphatic obstructions due to
-:::-Parasitic plugs
-:::-Tumor cells
-:::-Chronic starvation
-*Decrease of venous blood flow due to congestive hard failure
-*Decrease in colloid osmotic pressure due to deficiency of plasma protein
-*Increased of permeability of blood capillary endothelium due to
-:::-Chemical  or mechanical injure
-:::-Allergic reaction after production of histamine
-=='''TYPES OF CONNECTIVE TISSUE'''==
-'''1) LOOSE  (ALVEOLAR)'''
-*Is a very common type
-*Has a delicate consistency and is
-:::-Flexible
-:::-Well vascularized
-:::-And not very resistant to stress
-*Support many structures that are  normally under pressure
-*Supports epithelial tissue
-:::-In glands
-:::-In the mucous membranes
-:::-In peritoneal and pleural cavities
-*Forms a -layer around '''small blood and lymphatic vessels''' and papillary layer '''of dermis in hypodermis'''
-*Fills the spaces between muscle and fibers
-*Is also called areolar tissue (has all components of connective tissue in equal parts
-''' 2) DENSE'''
-*Offer resistant and protection
-*Has the same components with the loose connective tissue  but '''Fewer cells''' and '''more collagen fibers'''
-*Is less flexible
-*Is more resistant to stress
-*Is of two different type in function of orientation of collagen fibers:
-:'''a. Irregular'''
--Fibers in '''bundles without orientation'''
--form a 3-dimentional network
--provide resistance to stress from all directions
--is found close associated with loose connective tissue
-::'''b. Regular'''
--fibers in bundles  are arranged with''' linear orientation'''
--in the same direction with the exerted stress
--and offers great resistance to traction forces
--is found in tendons and ligaments
--due to the fact that are rich in collagen fibers are '''white and inextensible'''
--they have parallel closely packed bundles of collagen and
--a very small quantity of ground substance
--a few fibrocytes with elongated nuclei and sparse cytoplasm that is not revealed in H&E because it stains the same color with fibers
--The collagen bundles of tendons are '''enveloped''' by small amounts of '''loose connective tissue,''' with small vessels and nerves.
--are poorly vascularized so the repair of damage is very slow
--externally the tendon is surrounded by a '''sheath of dense irregular tissue'''
--Synovial cells of Mesenchymal origin form a sheath, from 2 layers.
--The space between these two layers is filled with fluid similar to the fluid of synovial joints rich in water, proteins,Hyaluronate  and other GAGs
--Acts as lubricant
-'''3) SPECILIZED'''
-'''Is of two types'''
-'''a. Reticular connective tissue'''
-*Is a 3-dimesnional network
-*formed by reticular fibers of type III collagen
-*produced by reticular cells ( specialized fibroblasts)
-*heavily glycosylated reticular fibers provide the architectural framework for cell attachment
-*is found in hematopoietic and lymphoid organs : bone marrow, Lymph nods, spleen
-*the reticular cells are dispersed along this framework forming a''' spongelike structure''' in which cells and fluids are freely mobile
-'''b. Mucous connective tissue'''
-*is found in the umbilical cord and fetal tissue
-*has an abundant ground substance
-*composed mostly of hyaluronic acid
-*making it a jellylike tissue named '''Wharton’s Jelly (in umbilical cord)
-'''
-*is found also in '''pulp cavity of young teeth'''