Contents · 12 sections
In a nutshell. Connective tissue is the most diverse tissue in the body, originating from the mesenchyme. It has few cells and abundant intercellular substance (fibres + amorphous ground substance). Classification: proper connective tissue (loose — subcutaneous, between organs; dense — irregular in the dermis, regular in tendons), specialized (bone, cartilage, blood, lymph, reticular, adipose). Cells: fibroblasts, macrophages, mast cells, plasma cells, adipocytes. Fibres: collagen (I — skin, bone; II — cartilage; III — reticular; IV — basement membrane), elastic, reticular. Collagenopathies: Ehlers-Danlos syndrome, osteogenesis imperfecta, Marfan syndrome.
1. Origin and general characteristics
- Derived from mesenchyme (middle germ layer).
- The main feature is the predominance of extracellular matrix over cells.
- Functions: structural support, trophic, protective, regulatory, plastic (regeneration).
- Extracellular matrix = fibres + amorphous ground substance (gel) + tissue fluid.
2. Classification
| Group | Type | Localization |
|---|---|---|
| Proper CT | Loose connective tissue | Subcutaneous tissue, organ stroma |
| Proper CT | Dense irregular connective tissue | Dermis, organ capsules |
| Proper CT | Dense regular connective tissue | Tendons, ligaments, fasciae |
| Specialized | Adipose tissue (white/brown) | Subcutaneous, omentum; brown — interscapular in infants |
| Specialized | Reticular tissue | Bone marrow, lymph nodes, spleen |
| Specialized | Cartilage (hyaline, elastic, fibrocartilage) | Articular surfaces, trachea, auricle |
| Specialized | Bone tissue | Skeleton |
| Specialized | Blood and lymph | Blood vessels, lymphatic vessels |
3. Connective tissue cells
- Fibroblasts/fibrocytes — synthesis of collagen, elastin, proteoglycans.
- Macrophages — phagocytosis, antigen presentation, cytokines.
- Mast cells — histamine, heparin, tryptase; IgE-mediated response.
- Plasma cells — antibody production.
- Adipocytes — lipid storage, endocrine function (leptin, adiponectin).
- Mesenchymal stem cells — regeneration.
- Pericytes — around capillaries, smooth muscle cell precursors.
4. Collagens — main types
| Type | Localization | Associated diseases |
|---|---|---|
| I | Skin, bone, tendons, dentin — 90% of body collagen | Osteogenesis imperfecta, Ehlers-Danlos syndrome |
| II | Hyaline and elastic cartilage, vitreous body | Stickler syndrome, chondrodysplasias |
| III | Reticular fibres (liver, spleen, vessel walls, early scars) | Vascular Ehlers-Danlos syndrome |
| IV | Basement membrane (no fibrils, network) | Alport syndrome, epidermolysis bullosa |
| V | Hair, placenta, polymerizes with type I | Classical Ehlers-Danlos syndrome |
| VII | Anchoring fibrils of the epidermis | Dystrophic epidermolysis bullosa |
5. Collagen synthesis
- Translation of preprocollagen in the ER.
- Hydroxylation of proline and lysine (requires vitamin C); deficiency → scurvy.
- Glycosylation.
- Procollagen triple helix → secretion into the ECM.
- Cleavage of N- and C-propeptides by peptidases.
- Self-assembly into fibrils, cross-linking by lysyl oxidase (Cu²⁺-dependent; deficient in Menkes disease).
6. Elastin and Microfibrils
- Elastin is the main protein of elastic fibers; provides reversible stretching (lungs, aorta, skin).
- Synthesized as tropoelastin, cross-linked via desmosine and isodesmosine.
- Microfibrils contain fibrillin-1 — the scaffold for elastin.
- Mutation in fibrillin-1 (FBN1) → Marfan syndrome.
- Elastin deficiency → supravalvular aortic stenosis (Williams syndrome).
7. Extracellular Matrix
- Proteoglycans = protein core + GAGs (chondroitin sulfate, keratan sulfate, dermatan sulfate, heparan sulfate, hyaluronic acid).
- Hyaluronan is a very large molecule, creates a "cushion" (joints, vitreous body).
- Adhesive glycoproteins: fibronectin, laminin, tenascin, vitronectin — bind cells to the ECM via integrins.
- The ECM is not passive: it participates in signaling and storage of growth factors (TGF-β, FGF).
8. Cartilage Tissue
- Cells: chondroblasts (synthesis), chondrocytes (in lacunae).
- No blood vessels or nerves — nutrition occurs via diffusion.
- Hyaline — articular surfaces, trachea, costal cartilage; type II collagen predominates.
- Elastic — auricle, epiglottis; + elastic fibers.
- Fibrocartilage — intervertebral discs, pubic symphysis; more type I collagen.
- Poor regeneration — slow turnover, which is why the osteoarthritic process is irreversible.
9. Bone Tissue
- Cells: osteoblasts (osteoid synthesis), osteocytes (in lacunae), osteoclasts (resorption, derived from the monocyte lineage).
- Intercellular matrix: 60% mineral (hydroxyapatite Ca₁₀(PO₄)₆(OH)₂), 30% organic (type I collagen, osteocalcin, osteopontin), 10% water.
- Two types: compact (cortical) and spongy (trabecular).
- Remodeling is a constant balance between synthesis and resorption.
- Regulated by PTH (↑ resorption), calcitonin (↓), vitamin D (↑ absorption), estrogens (↓ resorption), RANKL/OPG system.
10. Adipose Tissue
- White (WAT) — main triglyceride reserve; endocrine function (leptin, adiponectin, resistin).
- Brown (BAT) — thermogenesis via UCP1 (uncoupling protein); rich in mitochondria; present in newborns and in small amounts in adults.
- Beige — induced by cold from white adipose tissue; intermediate phenotype.
- Obesity — adipocyte hyperplasia and hypertrophy; associated with insulin resistance, atherosclerosis, oncology.
11. Collagenopathies and Hereditary Syndromes
- Osteogenesis imperfecta (type I collagen): brittle bones, blue sclerae, hearing loss. Types I–IV.
- Ehlers-Danlos syndrome: joint hypermobility, skin extensibility, vascular fragility (especially vascular type — type III collagen).
- Marfan syndrome (FBN1): tall stature, arachnodactyly, lens ectopia, mitral valve prolapse, aortic aneurysm.
- Alport syndrome (type IV collagen): nephritis, deafness, eye pathology; X-linked dominant is more common.
- Scurvy (vitamin C deficiency): impaired proline hydroxylation → defective collagen → bleeding gums, loose teeth.
- Menkes disease (copper transport defect): lysyl oxidase is inactive → defective collagen and elastin cross-linking.
12. FAQ
Why do previously normal wounds break down in scurvy?
Without vitamin C, proline hydroxylation is impaired → unstable triple helix → old scars break down, new ones do not form. Therefore, petechiae appear, gums bleed, and teeth become loose.
How does osteoporosis differ from osteomalacia?
Osteoporosis is a decrease in total bone mass with normal mineralization (reduction of both organic and mineral components). Osteomalacia is impaired mineralization (vitamin D deficiency) with a normal osteoid — the bone is "soft".
Why doesn't cartilage regenerate?
No blood vessels → slow delivery of precursors; chondrocytes rarely divide; the ECM is dense and impedes cell migration. Therefore, in osteoarthritis, articular cartilage damage is irreversible.
What is the key difference between reticular fibers and type I collagen fibers?
Reticular fibers are made of type III collagen, thin, net-like, argyrophilic (silver-staining via Foot's method); they form the stroma of parenchymatous organs. Type I collagen forms thick bundles with a powerful supportive function.
Why is the aorta affected in Marfan syndrome?
Fibrillin-1 defect → instability of elastic fibers in the aortic media → medial necrosis → progressive dilation, dissection, rupture. Screening via echocardiography and CT angiography; prophylactic treatment with β-blockers, sartan medications.
See also: Systemic connective tissue diseases · Osteoporosis · Marfan syndrome · Osteogenesis imperfecta · Histology Catalog