June 20 - Part 1 Connective Tissue Notes

Connective Tissue: Histology and Pathophysiology

General Introduction

  • Connective tissue is widespread throughout the body.

  • It exists in various forms (solid, semi-solid, liquid).

    • Examples: bone (hard), cartilage (semi-hard), blood (liquid).

  • All connective tissues originate from mesenchymal tissue during embryonic development.

Mesenchymal Tissue

  • Embryonic connective tissue derived from the mesoderm.

  • Source of stem cells.

  • Mesenchymal cells are star-shaped.

  • Found in embryos and umbilical cords.

  • The umbilical cord contains a unique type of embryological connective tissue.

Connective vs. Epithelial Tissue

  • Connective tissue has a higher concentration of extracellular materials compared to epithelial tissue.

Components of Connective Tissue

  • Fibers

  • Extracellular material (ground substance)

  • Various cells

  • Functions:

    • Support

    • Carries blood vessels

    • Enables diffusion

    • Supports skin and tendons

    • Forms the skeleton

    • Wound repair, tissue repair, and regeneration

Proportions

  • The proportion of cellular, fibers, and ground substance varies depending on the specific tissue type.

Types of Connective Tissue

  • Embryonic Connective Tissue

    • Mesenchymal connective tissue

    • Mucus connective tissue (Wharton's jelly in the umbilical cord): unique ground substance, Function: Resilience to protect arteries and veins in the umbilical cord from being squeezed and impairing flow. Feels like gel in the heel of sneakers.

  • Connective Tissue Proper

    • Loose connective tissue: Abundant extracellular material, fewer fibers.

    • Dense connective tissue: Densely packed fibers.

      • Dense Regular: Parallel fiber arrangement.

      • Dense Irregular: Irregular fiber arrangement.

        • Fiber arrangement influences strength/weakness.

  • Specialized Connective Tissue

    • Adipose tissue

    • Reticular tissue

    • Elastic tissue

    • Mucus connective tissue

    • Cartilage

    • Bone

    • Blood

Cell Derivation

  • Mesenchyme gives rise to fibroblasts, cartilage cells, bone cells, and blood cells.

Connective Tissue Cells

  • Fibroblasts

  • Mast cells

  • Macrophages

  • Plasma cells

  • Fat cells (adipocytes)

  • Cartilage, bone, and blood cells

Fixed vs. Wandering Cells

  • Fixed cells: Non-motile (e.g., fibroblasts, fat cells, fixed macrophages).

    • Fixed macrophages: Located in specific tissues, with specific names.

      • Examples: mesangial cells (kidney), Kupffer cells (liver).

  • Wandering cells: Motile (e.g., lymphocytes, plasma cells, leukocytes).

    • Derived from hematopoietic stem cells.

Specific Cell Types

  • Fibroblasts: Secrete the matrix and collagen fibers.

  • Macrophages: Phagocytic cells derived from blood monocytes.

    • Wandering (monocytes) or fixed (specific organs).

  • Plasma cells: Antibody-producing cells derived from B cells.

  • Mast cells: Involved in immediate hypersensitivity/allergic reactions.

  • Fat cells (adipocytes): Store triglycerides.

Fibroblasts in Detail

  • Most common cell in connective tissue.

  • Produce extracellular matrix.

  • Two states: active (fibroblast) or quiescent (fibrocyte).

    • Fibroblast: Elongated, active, basophilic with prominent nucleoli.

    • Fibrocyte: Rounded, quiescent, less basophilic.

  • Can be activated under stress to make materials.

  • Essential for wound healing.

    • Proliferate and produce more fibers when stimulated.

Mast Cells in Detail

  • Involved in immediate hypersensitivity/allergic reactions.

  • Large cells with numerous granules.

  • Contain histamine, slow-reacting substances of anaphylaxis (SRSAs), and chemotactic factors.

  • Found in the dermis, GI tract, around blood vessels, and in the respiratory system.

  • Granules release heparin (anticoagulant) and bradykinin (nerve irritant).

Histamine

  • Responsible for a large part of the inflammatory response.

  • Makes blood vessels leaky, causing swelling.

  • Nerve irritant causing pain.

  • Increases blood flow to tissues, causing warmth.

  • Leads to allergies, asthma, and anaphylactic shock.

  • Causes vasodilation.

  • Regulated release (not constitutive).

  • Degranulation process:

    • Two IgE antibodies bind to the mast cell surface.

    • Antigen binds between the antibodies.

    • Activates cyclic AMP.

    • Calcium influx.

    • Fusion of granules and secretion (exocytosis) of heparin, histamine, and bradykinin.

    • Release of leukotrienes (inflammatory mediators) from the membrane.

      • Leukotriene inhibitors used in asthma treatment (e.g., montelukast).

Macrophages in Detail

  • Phagocytic cells derived from blood monocytes (histiocytes).

  • Oval-shaped with an eccentric nucleus.

  • May contain ingested material.

Plasma Cells in Detail

  • Involved in acquired immunity.

  • Source of antibodies (IgG, IgM, IgA, IgD, IgE).

  • Basophilic with nucleoli.

  • Nucleus has a cartwheel shape.

  • Eccentric nucleus with a clear Golgi zone.

Adipocytes in Detail

  • White fat (white adipocytes): Store triglycerides in one large lobule with the nucleus pushed to the side. Exists on a reticular network, not free-floating.

  • Bone marrow:

    • Erythroid/myeloid until age 8.

    • Flat bones (skull, sternum, iliac crest) make blood.

    • Long bones (femur, humerus) filled with fat (yellow marrow) after age 8.

  • Fat deposition is related to sex hormones.

    • Panniculus adiposus (baby fat): Layer of white fat in young children.

    • Females: Fat deposited in breasts, hips, and buttocks.

    • Males: Fat deposited in the brain and abdominal cavity.

  • Brown fat: Multilocular, thermogenic fat with multiple vesicles, highly vascular, and many mitochondria.

    • Breaks down inefficiently, releasing heat

    • Infants: Provides heat for inactive infants.

    • Adults: Between the scapula, more in females.

    • Activated when cold (Oswald's electric blanket effect).

    • Also found in armpits and mediastinum (in infants).

Connective Tissue Fibers

  • Collagen fibers

  • Elastic fibers

  • Reticular fibers

Collagen Fibers

  • Most abundant protein in the body.

  • Provide tensile strength and the ability to withstand stress.

  • Multiple types exist.

    • Types that form fibers (skin, tendon).

    • Type IV collagen forms a network in the basement membrane.

  • Biochemically similar to collagen, but physically different.

Reticular Fibers

  • Type III collagen.

  • Found with smooth muscle and in organs that change volume.

  • Basis of lymphatic/hematopoietic organs.

  • Found in the basement network.

Elastic Fibers

  • Rich in glycoproteins and elastin.

  • Allow stretching and recoil.

  • Found in organs that deform (heart, skin, blood vessels, lungs).

  • Elastic filaments/ligaments in the vertebral column (ligamentum flavum) and neck (ligamentum nuchae).

  • Make up the vocal cords.

Collagen Types

  • Type I: Skin, tendons, bone, dentin (responds to tension).

  • Type II: Cartilage, vitreous humor (resists pressure).

  • Type III: Reticular fibers (structural framework).

  • Type IV: Basement membrane (filtration).

Collagen Characteristics

  • Wavy appearance, acidophilic.

  • Periodicity (repeating subunits).

  • Procollagen is the precursor inside the cell.

  • Tropic collagen forms outside the cell, followed by collagen fibrin.

  • Vitamin C is essential for collagen formation.

  • Collagen and elastin are insoluble and strong.

  • Made up of a triple helix of amino acids.

    • Glycine is the predominant amino acid.

    • Hydroxyproline and hydroxyglycine are modified amino acids found predominantly in collagen.

  • DNA, rough ER, and Golgi are involved in collagen synthesis.

Collagen Synthesis

  • Procollagen subunits have a head and tail.

  • Linked together in a long chain.

  • Procollagen layers are laid down with a one-third overlap of head regions.

  • Overlap explains the striations in collagen fibers.

Defects in Collagen Synthesis

  • Osteogenesis imperfecta: Spontaneous bone fractures, cardiac damage, hearing loss.

  • Ehlers-Danlos syndrome: Hypermobility of digits, risk of aortic/intestinal rupture.

  • Scurvy: Lack of vitamin C leading to ulceration of gums, hemorrhage, corkscrew-shaped hairs, bruising.

  • Eyes tend to be pale, loss of teeth, bleeding of the eye, the eyes are sunken

Elastin

  • Found in vocal cords, aorta, arteries.

  • Rich in glycine and proline.

  • No hydroxyproline or hydroxylysine.

  • Chains are coiled like rubber bands.

Marfan Syndrome

  • Weakness/deficiency of elastic fiber synthesis.

  • Reduced elasticity in the lung (compliance).

  • Valvular prolapse.

  • Abraham Lincoln may have had Marfan syndrome.

  • Pectus excavatum (indented chest)

  • Dilation of the aorta

  • Long fingers, long limbs

  • Lenses can become dislocated\n

Reticular Fibers

  • Support capillaries.

  • Important in the nervous system, muscle fibers, and fat.

  • Found in the basement membrane and capsules around the spleen and lymph nodes.

  • Blood cells are made near reticular fibers.

  • Form a network.

Ground Substance

  • Gel-like material found in connective tissue and cartilage.

  • Contains glycosaminoglycans (GAGs) like hyaluronan.

Glycosaminoglycans (GAGs)

  • Hyaluronan provides viscosity in joints and under the skin.

  • Aids lubrication and prevents bacterial entry.

  • Hyaluronidase digests hyaluronan, reducing viscosity.

  • Proteoglycans are GAGs mixed with proteins.

  • Negatively charged GAGs attract water, enabling cartilage to resist compressive forces.

Ground Substance Components

  • Hyaluronic acid/hyaluron

  • Chondroitin sulfate

  • Heparin

Edema

  • Swelling from fluid flow into tissues.

  • Hydrostatic and osmotic pressure push fluid into tissues.

  • Drained via lymphatics.

  • Based on the collagen network.

Types of Connective Tissue (Revisited)

  • Loose, dense regular, or irregular.

Loose Connective Tissue

  • Areolar connective tissue supports the epithelium.

  • Found in the lamina propria of the GI tract.

  • Not very resistant to stress.

  • Found between muscle cells.

Dense Connective Tissue

  • Lots of fibers.

  • Dense irregular and dense regular.

Dense Regular Connective Tissue

  • Fibers in a parallel array like in a tendon.

  • Strong but inherently weak.

  • Collagen fibers resist tension in a unilateral direction.

  • Weakness when stress comes perpendicularly.

  • Attaches muscle to bone (series elastic component) and generates tension.

Dense Irregular Connective Tissue

  • Fibers are irregularly arranged to respond to stress in multiple directions.

  • Found under the skin.

  • Resists pulling.

Other Connective Tissue Types

  • Adipose and reticular tissue.

  • Mucoid connective tissue with Wharton's jelly in the umbilical cord resists compression.

Connective Tissue Cells Bioactivity

  • The fat are not static. They have really, they produce lots of bioactive, molecules.

  • They make the steroids, they make reproductive hormones, they make vasoactive compounds that control blood pressure.

  • The professor also mentioned about cellulite related to irregular adipose tissue.