04. Connective Tissue & Cartilage II

Connective tissue is composed of:

• Cells: Includes fibroblasts, adipocytes, macrophages, and mast cells.
• Fibers: Collagen, elastic, and reticular fibers provide strength and elasticity.
• Ground Substance: A gel-like material that fills the space between cells and fibers, containing water, proteins, and polysaccharides.

Types of cartilage include:

Hemopoiesis is the process of blood cell formation, occurring primarily in the bone marrow. It involves:

1. Stem Cell Differentiation: Hematopoietic stem cells differentiate into various blood cell lineages.
2. Production of Red Blood Cells: Erythropoiesis leads to the formation of red blood cells.
3. Production of White Blood Cells: Leukopoiesis leads to the formation of white blood cells.
4. Production of Platelets: Thrombopoiesis leads to the formation of platelets from megakaryocytes.

Muscle tissue functions include:

• Movement: Facilitates body movement and locomotion.
• Posture Maintenance: Helps maintain body posture and position.
• Heat Production: Generates heat through muscle contractions, aiding in thermoregulation.

The cardiovascular system consists of:

• Heart: The muscular organ that pumps blood throughout the body.
• Blood Vessels: Includes arteries, veins, and capillaries that transport blood.
• Blood: The fluid connective tissue that carries oxygen, nutrients, hormones, and waste products.

The two main components of connective tissue are Cells and Extracellular matrix (ECM).

The two branches of the extracellular matrix (ECM) in connective tissue are the fibrillar component and the amorphous component (ground substance).

All connective tissues originate from embryonic mesenchyme, which develops mainly from the mesoderm, the middle layer of the embryo.

The -blasts produce and secrete all types of fibers of the extracellular matrix (ECM) and will eventually become -cytes.

Mesenchymal cells can differentiate into various cell types:

1. Lipoblast → Adipose cell
2. Fibroblast → Fibrocyte
3. Chondroblast → Chondrocyte
4. Osteoblast → Osteocyte

Mesenchymal cells differentiate into hematopoietic progenitors that originate in bone marrow. They function for a short period as needed and then die by apoptosis, primarily found in loose connective tissue and capillaries.

Hematopoietic stem cells can differentiate into various cell types including:

1. Red blood cells
2. Megakaryocytes (which produce platelets)
3. Plasma cells
4. Lymphocytes (e.g., B lymphocytes)
5. Neutrophils
6. Eosinophils
7. Basophils
8. Monocytes (which differentiate into macrophages)
9. Osteoclasts

Apoptosis is significant as it allows migratory/wandering cells, such as those derived from mesenchymal cells, to die after fulfilling their short-term functional roles, thus maintaining homeostasis in connective tissue.

The two main categories of connective tissue found in adults are Proper and Specialized.

Proper connective tissue is divided into Loose and Dense connective tissue.

Dense connective tissue is further divided into Regular and Irregular connective tissue.

Specialized connective tissue includes Adipose, Reticular, Elastic, Supporting, and Blood.

The two types of Supporting connective tissue are Cartilage and Bone.

Adipose tissue is characterized by:

• Large, round adipocytes: These cells have thin cell membranes.
• Fat droplets: The large, clear area inside the adipocyte is primarily composed of fat.
• Cell structure: Each adipocyte contains a nucleus (a small, dark spot) and cytoplasm.

Reticular connective tissue is characterized by:

• Network of reticular fibers: These fibers form a mesh-like structure.
• Fibroblasts: Cells that produce the fibers are present within the network.
• Blood cells: The tissue contains various blood cells embedded in the reticular framework.

Elastic connective tissue is defined by:

• Wavy elastic fibers: These fibers run parallel to each other, providing elasticity.
• Fibroblasts: Cells that produce the elastic fibers are also present, contributing to the tissue's structure.

Cartilage tissue is composed of:

• Chondrocytes: These cartilage cells are located within lacunae.
• Matrix: The surrounding matrix is stained purple and pink, providing structural support.

Bone tissue is characterized by:

• Concentric rings (osteons): These structures surround a central canal, providing strength and support.
• Central canal: A single white oval in the center that contains blood vessels and nerves.

Blood tissue is composed of:

• Red blood cells (erythrocytes): Appearing as pink circles, they are responsible for oxygen transport.
• White blood cells (leukocytes): Scattered throughout the blood, these cells are involved in immune response.

The three types of adipocytes that differentiate from lipoblasts are multilocular adipocytes, beige adipocytes, and unilocular adipocytes.

Unilocular adipocytes are characterized by a large lipid droplet that occupies most of the cell volume, with the nucleus pushed to the periphery of the cell.

Multilocular adipocytes contain several lipid droplets and mitochondria within the cell, while unilocular adipocytes have a single large lipid droplet.

Mesenchymal stem cells differentiate into fibroblasts and lipoblasts, with lipoblasts further differentiating into various types of adipocytes.

Beige adipocytes are found in the following regions:

• Interscapular
• Perirenal
• Cervical
• Axillary
• Supraclavicular
• Periaortic
• Paravertebral
• Suprarenal

In neonates, beige adipocytes comprise 2-5% of body fat, while in adults, they make up about 1%.

The main types of collagen fibers and their associated proteins are:

The differences in structure among collagen fibers, reticular fibers, and elastic fibers are:

Reticular fibers consist mainly of type III collagen that is heavily glycosylated, which produces black argyrophilia when subjected to silver staining.

Reticular fibers serve as a supportive stroma (net) in lymphoid and hematopoietic organs.

Reticular fibers consist mainly of type III collagen that is heavily glycosylated, and they are visualized using the silver impregnation technique, which produces a black appearance against a light background.

Reticular fibers serve as a supportive stroma (net) in lymphoid and hematopoietic organs, providing structural support to these tissues.

The primary type of collagen found in reticular connective tissue is type III collagen, also known as reticulin.

Reticular connective tissue is primarily found in the following locations:

1. Bone marrow
2. Thymus
3. Lymph nodes
4. Spleen
5. Liver

The reticular fibers in reticular connective tissue are produced by fibroblasts, also referred to as reticular cells.

Elastic fibers are primarily composed of the proteins elastin and fibrillin.

Elastic fibers are interspersed and thinner than type I collagen fibers.

Marfan syndrome is associated with elastic connective tissue, specifically involving the fibrillin-1 (FBN1) gene.

Elastic connective tissue allows for stretching and bending, providing flexibility to structures such as artery walls.

The initial component of elastic fiber formation is 10-nm-diameter microfibrils composed of fibrillin, which are secreted by fibroblasts.

Elastin is deposited on the scaffold of microfibrils, forming growing, amorphous composite structures. As elastin accumulates, it occupies most of the structure while fibrillin remains visible at the edges.

Fibroblasts secrete both fibrillin to form the initial microfibrils and elastin to deposit on these microfibrils, contributing to the formation of elastic fibers.

Cartilage serves several key functions:

1. Support: It supports organs, particularly in the walls of airways such as the nose, trachea, and bronchi.
2. Tension Resistance: It withstands tension at the articular surfaces of bones, providing stability and cushioning.
3. Growth Template: It forms the template for the growth of long bones, particularly in the fetal skeleton and at the epiphyseal growth plate.

• Avascular: Cartilage does not have blood vessels.
• Lack of lymphatics and innervation: It does not contain lymphatic vessels or nerve fibers.
• Low metabolic activity: Cartilage has a reduced rate of metabolism, which affects its healing capacity.

Nutrients diffuse to cartilage from:

1. Adjacent dense connective tissue (perichondrium): Supplies nutrients through diffusion.
2. Synovial fluid in knee joints: Provides nutrients directly to the cartilage in joint areas.

1. Hyaline cartilage
2. Elastic cartilage
3. Fibrocartilage

Hyaline cartilage is found in the following locations:

• Nose cartilage
• Larynx
• Trachea
• Respiratory tract cartilage
• Costal cartilage
• Articular cartilage of joints

Elastic cartilage is found in:

• External ear cartilage
• Epiglottis

Fibrocartilage is found in:

• Intervertebral discs
• Pubic symphysis
• Meniscus

Hyaline cartilage is the most abundant type of cartilage. Its key characteristics include:

• Glassy appearance (from the Greek word 'hyalos' meaning glass)
• Surrounded by perichondrium, except at articular surfaces
• Composed of type II collagen in the extracellular matrix (ECM)
• Second most flexible type of cartilage
• Serves as a temporary embryonic skeleton

The perichondrium is a layer of dense connective tissue that surrounds hyaline cartilage, providing it with nutrients and support. It is present except at articular surfaces, where cartilage is in direct contact with other bones.

The extracellular matrix of hyaline cartilage contains type II collagen.

Hyaline cartilage serves as a temporary embryonic skeleton, providing a framework for the development of the skeletal system before it is replaced by bone during growth.

The main types of cells found in cartilage are chondroblasts and chondrocytes.

• Chondroblasts: These are the cells responsible for producing the extracellular matrix (ECM) and are found in the growing cartilage.
• Chondrocytes: These are mature cartilage cells that maintain the cartilage matrix and are located within small spaces called lacunae.

The extracellular matrix (ECM) of cartilage is composed of:

• Water: Provides hydration and turgidity.
• Proteoglycan complexes: These are large molecules that trap water and contribute to the resilience of cartilage.
• Collagen fibers: These provide structural support and tensile strength to the cartilage.

The perichondrium is a layer of connective tissue that surrounds cartilage (except at the joints). It serves several important functions:

• Provides a source of nourishment for the cartilage.
• Contains perichondrial fibroblasts that can differentiate into chondroblasts for cartilage growth and repair.
• Acts as a protective layer for the cartilage tissue.

The first step in chondrogenesis is the condensation of mesenchymal cells.

The transcription factor Sox9 is crucial for the differentiation of mesenchymal cells into chondroblasts.

Chondroblasts produce collagen type II (COL2A1 gene) and aggrecan in the extracellular matrix.

Chondrocytes grow from within through a process known as interstitial growth.

The optional step that can occur is hypertrophy and bone formation.

Hyaline cartilage is characterized by:

1. Isogenous aggregates of chondrocytes found in lacunae.
2. Matrix areas:
   • Pericellular & Territorial Matrix: Surrounds chondrocytes, is GAG-rich, and basophilic.
   • Interterritorial Matrix: Rich in collagen and eosinophilic.

The two types of cartilage growth are Appositional and Interstitial growth:

1. Appositional Growth:

   • Increases the WIDTH of cartilage.
   • Involves chondroblasts depositing matrix on the surface of pre-existing cartilage, originating from the perichondrium.

2. Interstitial Growth:

   • Increases the LENGTH of cartilage.
   • Involves chondrocytes dividing and secreting matrix from within the lacunae of the matrix.

Water constitutes 60 - 80% of the weight of the ECM and is bound to glycosaminoglycans (GAGs).

The fibrillar part of the ECM contains Collagen Type II, and Type I is present in fibrocartilage.

The major proteoglycan in the ECM is Aggrecan, which has approximately 150 GAG side chains.

The three glycosaminoglycans (GAGs) found in the ground substance of the ECM are Chondroitin sulfate, Keratan sulfate, and Hyaluronic acid.

Chondronectin is a glycoprotein that binds chondrocytes to the extracellular matrix (ECM).

The aggrecan complex consists of a central hyaluronic acid chain with core proteins radiating outward. Each core protein is attached to sulfated glycosaminoglycans (GAGs), giving the aggregate a bottle-brush-like appearance. The aggrecan monomer is made up of approximately 150 short sulfated GAGs.

Elastic cartilage contains elastic fibers and type II collagens in its matrix. It is also characterized by the presence of a perichondrium.

Elastic cartilage is found in the auricula (outer ear), meatus (ear canal), and the epiglottis.

Elastic cartilage is very similar to hyaline cartilage but is distinguished by the presence of acidophilic elastic fibers in its matrix, which are stained nicely with fuchsin.

Fibrocartilage is a hybrid between cartilage and dense connective tissue, characterized by chondrocytes arranged in rows between thick bundles of collagen fibers (Type I and Type II). It provides mechanical durability and lacks a perichondrium, distinguishing it from other cartilage types.

Fibrocartilage is found in areas subject to pressure, including:

1. Intervertebral discs (anulus; ring)
2. Pubic symphysis
3. Knee menisci

Fibrocartilage contains Type I and Type II collagen fibers, which contribute to its mechanical durability, allowing it to withstand pressure and tension in various anatomical locations.

The main pathologies include:

1. Osteoarthritis (OA): Degeneration of articular (hyaline) cartilage.
2. Achondroplasia: A genetic condition caused by mutations in the FGFR3 gene, leading to dwarfism.
3. Tumors: Such as Chondromas and Chondrosarcomas.

Repair strategies for cartilage injuries include:

1. Cartilage grafts: Utilizing autologous transplantation and mesenchymal stem cell (MSC) therapy.
2. Joint replacement: Procedures such as hip and knee joint replacement (arthroplasty).

Cartilage has a poor healing potential primarily due to its avascularity, meaning it lacks a direct blood supply, which is essential for healing and regeneration.

The main categories of connective tissue are:

1. Proper

   • Loose
   • Dense
     • Regular
     • Irregular

2. Specialized

   • Reticular
   • Elastic
   • Adipose
   • Supporting
     • Cartilage
     • Bone
   • Blood

Adipose tissue is characterized by rounded cells with clear cytoplasm and thin, dark nuclei pushed to the periphery, resembling a honeycomb structure.

Reticular connective tissue appears as a network of thin, branching fibers forming a delicate mesh-like structure, with scattered dark-stained reticular cells within the meshwork.

Dense regular connective tissue is composed of bundles of parallel collagen fibers that appear as wavy lines, with scattered elongated fibroblast nuclei oriented along the fiber direction.

Cardiac muscle tissue consists of elongated, branched cells (cardiomyocytes) with visible striations (light and dark bands), interconnected by dark lines (intercalated discs), and centrally located nuclei.

Hyaline cartilage tissue features chondrocytes located within lacunae (small spaces), surrounded by a smooth, glassy extracellular matrix.

Nervous tissue is characterized by large neurons with prominent nuclei, surrounded by smaller glial cells and thin, elongated nerve fibers.

Blood tissue can be identified by numerous small, round, red-colored cells (red blood cells or erythrocytes) with a central pallor, scattered among a clear background (plasma).

Bone tissue displays osteons, which are circular structures with concentric rings of bone matrix (lamellae) surrounding a central canal (Haversian canal), with osteocytes visible within lacunae between the lamellae.

Skeletal muscle tissue is composed of elongated, cylindrical cells (muscle fibers) with multiple peripherally located nuclei and visible striations (light and dark bands).

Elastic connective tissue features thick, wavy, and branching elastic fibers, appearing as dark lines, interspersed with fibroblasts.