Histology of Connective Tissue

Overview of Connective Tissue

Connective tissue is one of the four major types of human tissues.
Composed of:
- Cells
- Extracellular matrix (ECM)
Clinical correlations:
- High blood pressure
- Ehlers-Danlos syndrome.
- Marfan syndrome.

Learning Objectives

By the end of this session, you will be able to:

Explain the function of common cell types found in connective tissue:
- Fibroblasts
- Macrophages
- Mast cells
- Plasma cells
- Leukocytes
- Adipocytes
- Mesenchymal cells
Identify structure and function of:
- Different types of fibers
- Components of ground substances in extracellular matrix.
Describe structural and functional features of different types of connective tissue:
- Loose
- Dense regular
- Dense irregular
- Reticular
- Mesenchyme
- White and brown adipose tissue.
Identify sites in the body where the various types of connective tissue can be found.
Recognize connective tissue cells at light and electron microscopic levels and relate structure to function.
Explain clinical correlations including:
- Marfan’s syndrome
- Ehlers-Danlos Type 3
- Scurvy
- Immediate hypersensitivity reactions
- Obesity
- MMPs in human disease
- Hyaluronic acid disassembly by microorganisms.

Introduction and Classification of Connective Tissue

Connective Tissue Components:
- Cells
- Extracellular Matrix

Classification of Connective Tissue

Embryonic Connective Tissue
Connective Tissue Proper
Specialized Connective Tissue

Embryonic Connective Tissue

Consists of Two Classes:

Mesenchyme CT
- Found in the embryo.
- Gives rise to almost all tissues in adult.
Mucoid CT
- Found in the umbilical cord.

Connective Tissue Proper

Two Subtypes:

Loose Connective Tissue
- Located under epithelia that:
  - Cover body surfaces
  - Line internal surfaces
- Associated with epithelium of glands.
- Surrounds blood vessels, muscles, and nerves.

Overview

Connective Tissue Proper Composition:
- Cells and extracellular matrix (ECM), consisting of fibers and ground substance.
- Functions:
- Cells produce matrix, store fat, phagocytose, provide immunological defense.
- Fibers provide strength and elasticity.
- Ground Substance:
- Gelatinous, providing padding, allowing diffusion.
- Functional characteristics depend on composition and arrangement of elements.

Dense Connective Tissue

There are Two Types of Dense Connective Tissue:

Dense Regular Connective Tissue
- Composed mostly of:
  - Bundles of Type I collagen fibers
  - Fibroblasts.
- Locations:
  - Found in:
  - Tendons
  - Ligaments
  - Aponeuroses (flat tendons).
Dense Irregular Connective Tissue
- Contains:
  - Mostly collagen fibers
  - Bundles of collagen oriented in various directions.
- Locations:
  - Found in:
  - Capsule of organs
  - Dermis of the skin
  - Submucosa of gastrointestinal tract (GIT).

Extracellular Matrix (ECM)

Components of ECM:

Different Types of Fibers:
- Collagen fibers
- Elastic fibers
- Reticular fibers.
Ground Substance made of:
- Proteoglycans
- Multiadhesive glycoproteins.

Fibers of the Connective Tissues

Collagen Fibers:

Found in:
- Tendons
- Organ capsules
- Dermis.
Synthesis:
- Collagen molecules synthesized in the rough endoplasmic reticulum (rER) of fibroblasts.
- Vitamin C-dependent for efficient synthesis of procollagen.

Clinical Correlation: Scurvy

Definition: Disease caused by vitamin C deficiency.
Importance of Vitamin C:
- Needed to produce stable triple helix procollagen in the rER.
Consequences: Lack of stability compromises skin, mucous membranes, blood vessels, and bone integrity.
Symptoms of Scurvy:
- Swollen, bleeding gums.
- Opening of previously healed wounds.

Ehlers-Danlos Syndrome

Definition: Rare genetic disorder caused by defective collagen synthesis.
Most Common Type: Characterized by unstable joints that are easily dislocated, hypermobile due to overstretched ligaments.

Elastic Fibers:

Found in:
- Elastic arteries (e.g., aorta)
- Lungs
- Ligaments
- Skin
- Vocal folds of the larynx
- Elastic cartilage (external ear).
Production: By fibroblasts, elastic properties due to random coiling of elastin molecules.

Clinical Correlation: Marfan Syndrome

Caused by mutation in the fibrillin gene (FBN1).
Affects cardiovascular, skeletal, and ocular systems.

Ground Substance

Characteristics:

Occupies spaces between cells and fibers.
Permits diffusion of gases, nutrients, and waste products.
Composed mainly of:
- Glycosaminoglycans (GAGs)
- Proteoglycans
- Multiadhesive glycoproteins.

Glycosaminoglycans (GAGs):

Long straight-chain polysaccharides composed of repeating disaccharide units.
Features:
- Sulfated and negative charge due to carboxyl groups.
- Includes:
- Dermatan sulfate
- Chondroitin sulfate
- Keratan sulfate
- Heparan sulfate
- Hyaluronic acid (non-sulfated)
- Heparin.
Function: Attract water, enable diffusion of water through ground substance.

Proteoglycans:

Large macromolecules with a core protein to which GAGs are covalently bound (look like a bottle brush).
Important proteoglycan: Aggrecan.
Components: GAGs like chondroitin sulfate and keratan sulfate.
Interacts with type II collagen to form a compression-resistant gel.
Proteoglycan aggregates with numerous monomers binding to hyaluronan (huge non-sulfated GAG).
Susceptibility: Damage due to cleavage of non-covalent bonds from UV exposure, free radicals.
Over a lifetime, reduction of aggregates results in skin wrinkling and osteoarthritis.

Cells of the Connective Tissue

Classification:

Fixed Cells:
- Fibroblasts
- Myofibroblasts
- Macrophages
- Adipose cells
- Mast cells
- Undifferentiated mesenchyme cells
- Pericytes.
Wandering Cells (transient):
- Lymphocytes
- Neutrophils
- Eosinophils
- Basophils
- Monocytes
- Plasma cells.

Fibroblasts:

Principal cells of connective tissue.
Synthesize:
- Collagen
- Elastin
- Reticular fibers
- Complex carbohydrates of ground substance.

Myofibroblasts:

Modified fibroblasts that have bundles of contracting actin filaments in cytoplasm.
Implicated in wound contraction leading to closure.

Macrophages:

Also known as tissue histiocytes.
Derived from monocytes in the bone marrow.
Features:
- Large indented or kidney-shaped nucleus.
- Contains lysosomes, vacuoles, finger-like projections.
Functions:
- Major roles in phagocytosis and immune function.

Mast Cells:

Related to blood basophils; arise from progenitors in bone marrow.
Found in:
- Areas around small blood vessels
- Skin
- Capsules of organs.
Granule contents:
- Histamine
- Slow-reacting substance of anaphylaxis
- Eosinophil/neutrophil chemotactic factors.
- Heparin.

Adipose Cells:

Adipocytes are 100 µm or larger and specialized for fat storage.
Types of Adipose Tissue:
- White (unilocular): Stores energy, functions as an endocrine organ producing:
- Angiotensinogen
- Steroids
- Leptin.
- Brown (multilocular): Contains multiple lipid droplets, more central nucleus.
- Rich in mitochondria containing cytochrome oxidase, granting brown color.
- Mostly present in newborns, most diminishes by 10 years.

Lymphocytes:

Small white blood cells, minimal cytoplasm with rounded, heterochromatic nuclei.
Play a crucial role in immune responses and found in increased numbers during inflammation.

Plasma Cells:

Found in Lamina propria of:
- GI tract
- Respiratory tract
- Urogenital tract
- Salivary glands
- Lymph nodes
- Hemopoietic tissue.
Derived from B-lymphocytes, produce specific antibodies.

Neutrophils, Monocytes, and Eosinophils:

Rapidly migrate from blood to connective tissues in response to injury/inflammation.
Eosinophils contain granules with major basic protein, effective against protozoan and helminthic parasites.

Basophils:

Functionally related to mast cells; least numerous of WBCs.
Originates in bone marrow, remains in circulation, and contains:
- Histamine
- Heparin
- Leukotrienes.