Connective Tissue

Connective Tissue:
Connective tissues are a group of tissues structurally composed of cells, fibers & ground substance, derived from mesoderm and are responsible for providing & maintaining form in the body.
• Intercellular matrix is maximum & cellular component is minimum
• Composed of cells & matrix (i.e fibers & ground substances)
• Mesodermal in origin
• Cells are widely scattered within the intercellular matrix.
* All connective tissues are developed from mesenchyme (except blood cells).
* Mesenchyme is mesodermal in origin.
• Only so-called connective tissue proper is not only connective tissue proper.
• Even bone, cartilage, blood & lymph are connective tissue & possess all the above characteristics.
• Only difference in what form, intercellular matrix exists.
Connective Tissue Intercellular matrix
Connective Tissue Proper Jelly-like, soft, Viscous
Cartilage More than semi-solid
Bone Solid
Blood & Lymph Fluid type
Basic classification: 
A) Embryonic connective tissue
1. Mesenchyme: 
Give rise to all other connective tissues
2. Mucous C.T (Wharton's Jelly):
Present in umbilical cord
B) Adult connective tissue
Derived from mesenchyme
1. Connective tissue proper
• Loose connective tissue
- Areolar C.T
- Adipose C.T
- Reticular C.T
• Dense connective tissue
- Regular C.T
- Irregular C.T
- Elastic C.T
2. Supporting Connective tissue
• Bone
- Compact
- Spongy
• Cartilage
- Hyaline
- Fibrous
- Elastic
3. Fluid connective tissue
• Blood
• Lymph
C.T-Connective Tissue

Why bones a cartilage are called connective tissue?
• Origin from mesenchyme (mesodermal in origin)
• Extracellular matrix (fibers and ground substances) are more than cells.
• Only difference is the matrix of other connective tissue is soft, viscous but,
• Matrix of cartilage → Semi-solid
• Matrix of bone → Solid

Why blood is called connective tissue?
• Mesodermal in origin
• Extracellular matrix (Plasma) is maximum whereas cellular substances are minimum
* In this case, the ground substance is → blood plasma, which has protein fibers floating around it.
Why blood is called specialized connective tissue?
Why blood is special than other connective tissue?

• Extracellular matrix (plasma) is fluid in nature,
• But in case of other connective tissue → extracellular matrix is in semisolid.
Components of connective tissues
1. Cells
2. Extracellular Matrix
(Intercellular matrix)

 • Fibers
 • Ground substances

Cells of connective tissues:
(Two types)
1. Fixed cells
2. Wandering cells
Fixed cells (Stationary cells)
• Non-motile
1. Fibroblasts
2. Chondroblasts
3. Osteoblasts
4. Adipose cell
5. Mast cell
6. Pigment cell
7. Reticular cell

Wandering cells (migratory cells)
• Motile, move one place to another
1. Neutrophils
2. Eosinophils
3. Basophils
4. Monocyte
5. Lymphocyte
6. Plasma cells
7. Macrophage
Types of WBC (Leukocyte)
• Neutrophils
• Eosinophils
• Basophils
• Monocyte
• Lymphocyte
These cells are usually present in blood.
Thus they migrate with the blood fluid.
B-Lymphocyte later differentiate into antigen producing cells called plasma cells.
Mnemonic: (NEB ML)
Immature cells- (Blast)
Mature cells- (Cyte)
• Fibroblast Connective tissue proper
• Chondroblast Cartilage
• Osteoblast Bone
Hematopoietic stem cells Blood cells
Immature (blast) Mature (cyte)
Fibroblast Fibrocyte
Chondroblast Chondrocyte
Osteoblast Osteocyte
Hematopoietic stem cells RBC, WBC, Platelets
• Most common principle cells in connective tissue
• Spindle-shaped
• Responsible for secretion of ground substances and fibers (extracellular matrix components)
• Fibroblast has irregularly branched cytoplasm.
• Mature cell - called as Fibrocyte
1. Fibroblasts synthesize protein such as collagen & elastin which form collagen, reticular & elastic fibers. (Fibro-fibers synthesis)
2. It also synthesizes glycosaminoglycans (GAGs), proteoglycans, and glycoproteins of ground substance.
3. They help in the healing of wounds by continued proliferation and simultaneous conversion into fibrocytes and cause scar formation.

Macrophages are large phagocytic cells derived from the bone marrow precursor cells.

Characteristic Feature:
• Phagocytic in nature

Macrophages derived from bone marrow precursor cells that divide, producing monocytes which circulate in the blood
& cross the wall of venules & capillaries to penetrate the connective tissue, where they mature & acquire the morphological features of macrophages.

Bone marrow precursor cells
Monocyte (of blood)
Enter into connective tissue
(Differentiate into)
• They digest particular organic molecules, foreign bodies, pathogens by phagocytosis process.
• Thus, helps in removing cell debris & damaged extracellular components
• Production of cytokines, chemotactic factors, & several other molecules that participate in inflammation, antigen presentation.
• They contribute to the immunological reactions of body
• Macrophages are the main antigen-presenting cells.
1) Fixed/Resting macrophages:
• These macrophages remain in a particular tissue.
Alveolar macrophage
Splenic macrophage
2) Wandering macrophages: 
• In tissue, macrophage gets a special name.
• Monocyte during infection or inflammation get to different tissue & get a different name.
Distribution of macrophages
Site Name of macrophages
Skin Langerhans's cell
Connective tissues Histiocytes
Brain Microglia
Lungs Alveolar macrophage
Liver Kuffer's cell
Spleen Red pulp & splenic macrophages
Lymph node Reticular cells
Bone Osteoclast

Reticulo-endothelial system
• Phagocytic cells occupying the endothelial lining & reticular space of connective tissue & mobile macrophages are collectively called reticulo-endothelial system.
• The total combination of monocyte, mobile macrophage, fixed tissue macrophages & few endothelial cells in bone marrow, spleen & lymph nodes is called reticulo-endothelial system.
• Also known as mononuclear phagocyte system
• Macrophage system

Reticuloendothelial cells/
(Distribution of macrophages)
In connective tissue → Histocytes
In blood → monocytes (precursors of macrophages)
In sinusoids of liver → Kupffer's cell
In the lymphoid tissue & lymph nodes → Reticular cells
In spleen → splenic & red pulp macrophages
In lung alveoli → Alveolar macrophages
In brain & spinal cord → Microglia
In bone → osteoclast

• Phagocytosis:
  Bacteria, dead cells (derbies), foreign particles

• Formation of antibodies
• Destruction of aging WBC & RBC
• Storage & circulation of iron.
Mononuclear phagocytic cells are derived from precursor cells in the bone marrow. These precursors develop into monocytes and dendritic cells, phagocytic cells that are released into the bloodstream. Some monocytes and dendritic cells remain in the general circulation, but most of them enter body tissues. In tissues, monocytes develop into much larger phagocytic cells known as macrophages.
The great majority of macrophages remain as stationary cells within the tissue, where they filter out and destroy foreign particles. Some of them break away, however, and wander through the circulation and within the intercellular spaces.
Cells of the mononuclear phagocyte system differ in appearance and name because of their various location.
For example,
Dendritic cells are found in many tissues, including the lungs, the skin, and the GIT, as well as throughout the lymphatic system.
Histiocytes are found in numerous subcutaneous tissues.
Kupffer cells line the sinusoids of the liver.
Microglia occur in nervous tissue, and alveolar macrophages are found in the air spaces of the lungs.
The mononuclear phagocyte system plays an important role in the destruction of worn-out aging red blood cells and the recycling of iron. Specialized macrophages, primarily those residing in the bone marrow, liver, spleen, break down old red blood cells and metabolize the hemoglobin (oxygen-carrying protein), thereby freeing the iron compound heme for the production of new red blood cells.
Alveolar macrophage of lungs phagocytose the harmful product present in smoke.
That's why the smoker's lung seems to be black.
Macrophage beneath the skin → digest the color of the tattoo.
It is the reason your tattoo of body could fade out.
Mast cells:

• Cell of the immune system
• Take part in inflammatory and allergic reactions
• Found throughout the connective tissue i.e beneath the skin, along the blood vessels, the mucosal lining of the respiratory, digestive tract
• Make store of various chemical like heparin, histamine
• Liberate histamine and other chemical mediators during allergic and inflammation reaction & promote vasodilation and increased vascular permeability (swelling, inflammation).
• Heparin acts as an anticoagulant in function.
Plasma cells

• Activated B lymphocyte differentiate into plasma cells.
• Plasma cells liberate protein called antibodies against the action of antigens & help in the defense mechanism.
Myeloma (Multiple myeloma)
→ is the malignant proliferation of plasma cells (cancer of plasma cells).
Pigment cells:
• Melanocytes are the pigment cells
→ derived from the embryonic neural crest,
• Found in the connective tissue of skin, pia-mater & choroid coat of eye.
• It gives black appearance wherever it present & protects the skin against the cosmic rays of the sun.
Adipocytes/Fat cell:
• Connective tissue cells specialized for the storage of neutral tats (TAG) for the production of heat.
- Two types: 
• White adipocyte
• Brown adipocyte
White adipocyte:
• Contain one huge droplet of lipid that makes up 85 % of cells volume
Brown adipocyte: 
• Their cytoplasm contains many small lipid droplets.
• They have numerous mitochondria.
• At birth it is maximal relative to body weight.
  In childhood, it is largely replaced by white cells.
Functions of adipocytes: 
• Acts as storage of lipids chiefly triglyceride i.e esters of fatty acids & glycerol.
• Acts as a cushion, shock absorber.
• Acts as an insulator, prevent excessive heat gain or loss through the skin.
• Maintain the visceral position (e.g kidney)

♥ Women has more fat content than male. That's why they are soft & smooth in touch.
Functions of connective tissue cells:
• Fibroblast, chondroblast, osteoblast → Production of respective fibers & ground substances
- Fibroblast → for connective tissue proper
- Chondro blast → for cartilage matrix
- Osteoblast → for bone matrix formation
• Plasma cells → Production of antibodies
• Mast cell → secrete histamine for inflammatory response & heparin → for anticoagulation action
• Adipose cell → store of neutral fats (TAG), heat production
• Macrophage → phagocytosis of foreign harmful particles

Distribution of connective tissue fibers
Collagen Fibre:
• White protein fibers formed from collagen protein
• Produce from fibroblast
• Fibers are arranged in numerous straight or wavy bundles.
• No branching present
• Non-elastic but has high tensile strength, to withstand strong tension.
• Commonly found in tendons, ligament, aponeurosis

Common Main Types of collagen fibers: 
Type-I collagen fiber
About 90% of collagen fibers are of Type-I
(chief constituents of organic part of bone)
- Skin
- Tendon
- Ligament
- Bone
- Fascia
- Scar tissue (that firm after wound healing)
Type-II collagen fiber
- Fibrocartilage (i.e intervertebral disc) 
- Hyaline cartilage (i.e articular surface of joint, larynx, trachea)
Type-III collagen fiber
- Large blood vessels
- Spleen
- Liver
- Kidney
- Uterus
- Smooth muscle
Type-V collagen fibers
- Fetal tissue
- Placenta
Reticular fibers
• Produced from a type of fibroblast called reticular cells.
• Composed of Type-III collagen fibers
• Fine short fibers which branch to form an extensive network for supporting soft tissues like liver, bone marrow and tissues of the lymphatic system
• Commonly known as the framework of lymphoid organs.

• Found in
- Spleen
- Lymph node
- Lymph nodules
- Bone marrow
- Liver
- Kidney
- Smooth muscle

* Reticular cell, a type of fibroblast
→ that produces Type-III collagen fibers which are used to produce reticular fibers.

So it seems Type-III collagen fibers & reticular fibers have common distribution.

Elastic fiber
• Yellow branching fibers composed of elastin protein, formed by fibroblast
• Highly elastic and give elasticity to the lungs, large blood vessels (i.e aorta)
• Found in
- Large blood vessels like the aorta, pulmonary artery
- Lung
- Vocal cords
- Ligamentum Flava
- Ligamentum nuchae

* For inspiration, diaphragm & external intercostal muscles act.
But for quite expiration, no muscles needed for active action.
• It occurs due to the elastic recoil tendency of the lung.
Elastic forces extended by the surface tension of the fluid lining of lung alveoli & elastic fibers of lungs.
Summary on connective tissue fibers distribution
Connective tissue has a variety of fibers distributed.
But still some organs & structure has abundant specific fibers.
Type-I collagen fibers
For tough structure
Type-II collagen fibers
Hyalin cartilage
Fibroelastic cartilage

Elastic cartilage
(has elastic fibers)
Reticular fibers
Lymphoid organs
Elastic fibers
For those that need elasticity
Large arteries for pumping action like heart.
Elastic cartilage
Difference between epithelial & connective tissue:
Epithelial tissue Connective tissue
Defined as a collection of closely aggregated polyhedral cells with very little intercellular substance covering the external & internal surfaces of the body. It is a group of tissues structurally composed of cells, fibers & amorphous ground substances derived from embryonic mesoderm & are responsible
for providing & maintaining form in the body.
Derived from all germ layers Derived from mesoderm (mesenchyme)
Generally devoid of blood vessels & get nutrition by diffusion from underlying blood vessels. Present blood supply
Maximum cellular element & minimum intercellular substance Maximum extracellular element & minimum cellular element
covering, absorption, secretion, sensory, lubrication 
Mechanical, storage, defense, repair, transport & regeneration
Role of ascorbic acid in collagen synthesis:
• Ascorbic acid (vitamin C) is an important co-factor for proline hydroxylase (enzyme) for collagen synthesis
• Vitamin C (ascorbic acid) is an essential cofactor during collagen biosynthesis.
• The hydroxylation occurs during protein synthesis and requires ascorbic acid (vitamin C) as a cofactor.
• Deficiency of vitamin C leads to deficiency in proline hydroxylation leading to less stable collagen & causes the formation of defective collagen and leading to scurvy.
• In scurvy, the collagen formed is unhydroxylated, relatively unstable, and subject to collagenolysis.
Collection of connective tissue which may appear as condensations on the surfaces of muscles.
• Clavipectoral fascia
• iliotibial tract 
• Deep cervical fascia (fascia coil)

Closed connective tissue sac lined with a synovial membrane filled with lubricating fluid
• Allows free movements
• Helps in lubrication
• Diminish friction

Ground substance: 
These are the amorphous, transparent colorless, homogenous substances that participate in binding cells to the fibers of the connective tissue.