HISTOLOGY - CONNECTIVE TISSUE PROPER

1. Connective Tissue Proper

2. Specialized Connective Tissue

Major classification of Connective Tissue

a. Cartilage

b. Bone

c. Blood

d. Hematopoietic Tissue (Myeloid and Lymphoid)

Specialized Connective Tissues

1. Envelopes muscle

2. Binds organs together

3. Forms the supporting framework of organs

Functions of Connective Tissue Proper

Loose Connective Tissue

• Contains more cells and ground substance, but fewer fibers.

• Functions: Binds organs, supports blood vessels and nerves, site for immune responses, and limits infections.

Dense Connective Tissue

Contains more fibers (mainly collagen), fewer cells.

• Types:

  • Dense Regular: fibers arranged in parallel (e.g., tendons, ligaments).

  • Dense Irregular: fibers arranged randomly (e.g., dermis of the skin).

Cartilage

Avascular, flexible support; made of chondrocytes and matrix

Bone

Mineralized tissue that supports body structure

Blood

Fluid connective tissue; composed of RBCs, WBCs, and platelets suspended in plasma

Hematopoietic Tissue

Found in bone marrow; produces blood cells (myeloid and lymphoid lineages)

Adipose Tissue

Stores fat, insulates, and cushions organs

Lymphoid Tissue

Involved in immune response (e.g., lymph nodes, spleen)

1. Cells

2. Extracellular matrix

Basic Composition of Connective Tissue Proper

Cells

• Fibroblasts (most common): secrete fibers and ground substance.

• Immune cells: plasma cells (produce antibodies), macrophages, mast cells, leukocytes.

Extracellular Matrix (ECM)

• Determines the tissue’s function and consistency.

• Composed of:

  • Ground Substance

  • Fibers

Ground Substance (Component of ECM)

• Gel-like consistency like Cytosol.

• Serves as a medium for nutrient and gas exchange.

• Made primarily of water, proteoglycans, glycosaminoglycans (GAGs), and glycoproteins.

Proteoglycans

• Composed of a core protein + attached glycosaminoglycans (GAGs).

• Function: provides hydration and resistance to compression.

Types of Glycosaminoglycans in Ground Substance:

1. Hyaluronic acid

2. Keratan sulfate

3. Chondroitin sulfate

4. Dermatan sulfate

5. Heparan sulfate

Hyaluronic acid

Most abundant; retains water; in skin care

Keratan sulfate

Found in cartilage and cornea

Chondroitin sulfate

Important in wound healing

Dermatan sulfate

In skin, blood vessels

Heparan sulfate

Found in basement membranes

Glycoproteins

Help in adhesion between cells and matrix.

1. Fibrillar Glycoproteins

• Fibrillin

• Smaller fibrillar glycoproteins

2. Fibronectin

3. Laminin

4. Thrombospondin

Fibrillar Glycoproteins

• Fibrillin: Essential for forming elastic fibers.

• Smaller fibrillar glycoprotein: Function not clearly defined.

Fibronectin

Binds to integrins on cell surfaces and components of ECM.

Functions of Connective Tissue Proper

• Support: Forms the structural framework (stroma) of organs.

• Binding: Connects tissues and organs.

• Protection: Contains immune cells to fight infections.

• Transport: Serves as a site for nutrient, waste, and gas exchange.

• Repair: Involved in wound healing and scar formation.

• Storage: Stores energy (in adipose tissue) and water.

Scars

are made of dense irregular connective tissue.

Edema

may occur when ground substance accumulates excess fluid.

Defects in fibrillin

are associated with Marfan syndrome

Wound healing

involves increased synthesis of collagen and GAGs.

Laminin

A non-fibrillar glycoprotein found in the basement membrane.

• Promotes cell adhesion, migration, and differentiation.

• Helps epithelial cells anchor to connective tissue.

Thrombospondin

A multi-domain glycoprotein involved in cell-matrix interactions.

• Cell-to-cell and cell-to-matrix communication.

• Important in wound healing, angiogenesis inhibition, and immune responses.

Extracellular Fibers of Connective Tissue

1. Collagen Fibers

2. Elastic Fibers

3. Reticular Fibers

Collagen Fibers

Provides tensile strength (resistance to pulling).

• Appearance:

  • White in fresh tissue.

  • Stains pink in H&E (acidophilic).

  • Unbranched and straight.

• Properties:

  • Made mostly of Type I collagen (also II, III).

  • Tensile strength greater than steel.

  • Inelastic but slightly flexible.

• Examples: Tendons, skin, ligaments.

Tendons, skin, ligaments

Where can you find Collagen Fibers

Elastic Fibers

Provides elasticity—can stretch and return to original shape.

• Appearance:

  • Yellowish in fresh tissue.

  • Wavy, thin, branching in H&E stains (pinkish-yellow refractile lines).

• Properties:

  • Can stretch up to 2x their resting length (LIMITED)

  • Composed of elastin and fibrillin.

• Produced by: Fibroblasts and mesenchymal cells.

• Examples: Large arteries (aorta), elastic ligaments, vocal cords.

Where can you find Elastic Fibers

Large arteries (aorta), elastic ligaments, vocal cords.

Reticular Fibers

Forms a supportive meshwork in soft tissues.

• Appearance:

  • Not visible in H&E; need silver stains (argyrophilic).

  • Branching and anastomosing (net-like).

• Properties:

  • Composed of collagen type III.

  • Thinner and weaker than type I collagen.

• Produced by: Reticular cells (a type of fibroblast).

• Examples: Liver, lymph nodes, spleen, bone marrow.

Where can you find Reticular Fibers

Liver, lymph nodes, spleen, bone marrow

7 Resident Cells of Connective Tissue Proper

1. Mesenchymal Cells

2. Fibroblasts

3. Fibrocytes

4. Reticular Black

5. Adipose Cells (Adipocytes)

6. Mast Cells

7. Resident Macrophages

Resident Cells

Permanent inhabitants; maintain the structure and function of connective tissue.

Mesenchymal Cells

• Stellate shape/Star shaped

• Stem Cell

• Develops in Fibroblast

• Abundant in Children and rare in adults

• Can differentiate into fibroblasts, adipocytes, etc.

Fibroblasts

• Most abundant cell type

• Responsible for synthesizing fibers and ground substance

• Activated during tissue repair

Fibrocytes

• Inactive (resting) form of fibroblasts

• Can be reactivated when needed.

Reticular Cells

• Specialized fibroblasts that produce reticular fibers

• Collagen Type III

• Most abundant in reticular tissues like lymphoid organs.

Adipose Cells (Adipocytes)

• Store lipids for energy (CYTOPLASM)

• Function as thermal insulators and shock absorbers.

• Appear empty (washed out) in histological slides due to dissolved lipid.

• Shape: Signet-ring (nucleus pushed to side).

• Largest storage

1. Brown Fat - Mitochondria: Children - Generates Heat

2. White Fat - Adults

Mast Cells

• WBC MIGRATION

• Large, ovoid cells with basophilic granules.

• Contain histamine, heparin, and inflammatory mediators.

Function:

• Initiate inflammation.

• Play a key role in allergic (Type I hypersensitivity) reactions.

• Involved in wound healing and defense against pathogens.

Resident Macrophages

• Also known as Histiocytes

• From monocytes of the blood - Phagocytosis

Function:

• Phagocytosis of debris, pathogens, and apoptotic cells.

• Participate in immune surveillance and antigen presentation.

2 Types of Visiting Cells

1. Inflammatory Macrophages

2. Plasma Cells

Visiting Cells

Migrate into tissue during injury or infection; part of immune or inflammatory respons.

Inflammatory Macrophages

• Monocyte - Macrophages

• In response to stimulus

• Differentiate from monocytes

• Migrate to the site of inflammation

Plasma Cells

• From B-Lymphocyte - Plasma Cell

• Produce Immunoglobulins (Antibodies)

Papillary Layer of the Dermis

• Location: Upper layer of the dermis, just below the epidermis.

• Tissue Type: Loose connective tissue.

• Function:

  • Supports the epidermis.

  • Facilitates exchange of gases, nutrients, and waste between the dermis and epidermis (via diffusion).

  • Contains capillaries, nerve endings, and immune cells.

  • Plays a role in thermoregulation and defense against infection.

Hypodermis (Subcutaneous Tissue)

• Location: Below the dermis.

• Tissue Type: Primarily adipose tissue with some connective tissue.

• Function:

  • Anchors the skin to underlying muscles or bones.

  • Provides insulation, energy storage, and shock absorption.

  • Allows mobility of skin over underlying structures.

Lamina Propria

• Location: Underneath the epithelial lining of mucous membranes (e.g., respiratory, digestive, urogenital tracts).

• Tissue Type: Loose connective tissue.

• Function:

  • Contains immune cells, capillaries, lymphatics.

  • Important for immune surveillance (acts as a barrier and host defense).

  • Anti-microbial and inflammatory role — houses cells like macrophages, plasma cells, and lymphocytes.

  • Supports the epithelium and connects it to underlying muscle.

Adventitia

• Location: Outermost connective tissue layer of organs that are not suspended in a cavity (e.g., esophagus, parts of the intestines, retroperitoneal organs).

• Tissue Type: Loose or dense irregular connective tissue.

• Function:

  • Anchors organs to surrounding tissues.

  • Provides support and allows passage of nerves and vessels.

Mucosa

• Epithelium

• Lamina propria (connective tissue)

• Muscularis mucosae (thin layer of smooth muscle)

Submucosa

Is a layer of denser connective tissue beneath the mucosa.

• Function: Supports mucosa and houses larger blood vessels, nerves, and lymphatics.

Loose Connective Tissue

PROVIDES STRENGTH

• High vascular

• Has abundant extracellular substance

• With haphazardly arranged fibers (No regular pattern)

Types of Loose Connective Tissue

1. Ordinary Loose Connective Tissue

2. Modified Loose Connective Tissue

Ordinary Loose Connective Tissue

• Collagen Fibers are PREDOMINANT

• FIBROBLAST are the predominant cells

• Provides strength

• Significant contributor

Modified Loose Connective Tissue

• Predominant cell is a MODIFIED VERSION OF FIBROBLAST

• Different fibrilar composition

Types of Modified Loose Connective Tissues

1. Adipose Tissue

2. Reticular Tissue

3. Elastic Tissue

4. Mucous Tissue

Adipose Tissue

• Largest storage site of energy

Functions:

• energy storage,

• thermal insulation,

• protection, and

• shock absorption.

2 Types of Adipose Tissue

1. Yellow/White Adipose Tissue

2. Brown Adipose Tissue

Yellow (White) Adipose Tissue

1. Most abundant in adults;

2. Stores energy;

3. Large unilocular fat droplets

Brown Adipose Tissue

1. Contains many mitochondria (gives brown color);

2. Abundant in infants;

3. Generates heat (non-shivering thermogenesis)

Reticular Tissue

Composed mostly of reticular fibers (type III collagen) and reticular cells.

• Function: Forms the stroma (supportive framework) for delicate organs.

Location:

• Liver

• Lymph nodes

• Spleen

• Bone marrow

• Hematopoietic organs

Elastic Tissue

• Composed primarily of elastic fibers, often arranged in parallel bundles.

• Function: Provides elasticity and allows recoil of tissue after stretching.

Histological Features

• Predominant fiber: Elastic

• Supporting fiber: Collagen

• Cell type: Fibroblasts

• Elastic fibers may branch and interconnect (anastomose)

Location

• Ligamentum flavum of vertebral column

• Suspensory ligament of the penis

• Walls of large arteries (e.g., aorta)

Mucous Tissue

• A gelatinous form of connective tissue found mainly in embryos and newborns.

• Rich in ground substance, especially hyaluronic acid.

• Contains fibroblasts and mesenchymal cells.

• Sparse fibers (mostly fine collagen).

Example

• Wharton's Jelly: Found in the umbilical cord of the fetus; protects blood vessels and prevents compression.

Dense Regular Connective Tissue

• Collagen fibers are tightly packed and arranged in parallel.

• Few fibroblasts, aligned between fiber bundles.

• Very little ground substance.

Histological Appearance:

• Appears wavy and parallel under a microscope.

• Minimal cellular elements; mostly collagen type I fibers.

Function of Dense Regular Connective Tissue

Provides great tensile strength in one direction (unidirectional stress).

Location of Dense Regular Connective Tissue

• Tendons – connect muscles to bones.

• Ligaments – connect bones to other bones.

• Aponeuroses – flat, sheet-like tendons.

Dense Irregular Connective Tissue

Structure:

• Collagen fibers are irregularly arranged in multiple directions.

• Provides resistance to stress from various angles.

• Fewer cells and minimal ground substance, but more than dense regular CT.
  

Histological Appearance:

• Appears disorganized and interwoven.

• Fibers cross each other in multiple planes.

Function of Dense Irregular Connective Tissue

Offers multidirectional strength and protection.

Location of Dense Irregular Connective Tissue

• Dermis of the skin

• Dura mater (outermost meningeal layer)

• Capsules of organs (e.g., kidneys, liver, spleen)

• Periosteum (bone covering)

• Perineurium (nerve covering)