Connective Tissue and Cartilage

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Lesson 5 of 5

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Connective Tissue and Cartilage

Introduction

Connective tissue (CT) is the most widely distributed tissue in the body, forming the structural framework of organs, transmitting mechanical forces, and providing an environment for cells to migrate, proliferate, and communicate. Unlike epithelium, CT is characterised by an abundant extracellular matrix (ECM) relative to cells. CT is derived from mesoderm (and neural crest, for craniofacial CT).

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Components of Connective Tissue

Cells:

Fibroblasts: The principal CT cell; synthesise and maintain ECM (collagen, elastin, proteoglycans); elongated, spindle-shaped with pale oval nucleus; active fibroblasts have more cytoplasm than quiescent fibrocytes.
Macrophages (histiocytes): Derived from circulating monocytes; phagocytose pathogens, cellular debris, and foreign material; present antigens via MHC II; identified by CD68, PGM1. Specialised forms: Kupffer cells (liver), alveolar macrophages, Langerhans cells (skin).
Mast cells: Derived from mast cell progenitors in bone marrow; contain cytoplasmic granules with histamine, heparin, tryptase, and chymase; degranulate in IgE-mediated (type I) hypersensitivity reactions. Stain metachromatically with toluidine blue (granules appear purple on blue background). c-KIT (CD117) marks mast cells.
Plasma cells: Terminally differentiated B cells; produce immunoglobulins; eccentric "clock-face" heterochromatin nucleus; abundant pale cytoplasm due to rER (antibody synthesis); paranuclear Golgi hof (pale area).
Adipocytes: Specialised cells for lipid storage; white adipose cells: large unilocular lipid vacuole, peripheral nucleus; brown adipose cells: multilocular vacuoles, central nucleus, abundant mitochondria (uncoupling protein UCP-1 thermogenesis).

Fibres:

Collagen fibres: Most abundant protein in the body; assembled from triple-helix procollagen → collagen fibrils → fibres. Appear eosinophilic (pink) on H&E; deep blue on Masson trichrome; yellow-orange on van Gieson (picro-Sirius red). Collagen types: I (bone, tendon, skin — most abundant), II (hyaline and elastic cartilage), III (reticular fibres — fetal skin, liver, spleen, lymph nodes), IV (basement membranes), VII (anchoring fibrils — dermal-epidermal junction), XVII (hemidesmosomes).
Elastic fibres: Composed of elastin (cross-linked by lysyl oxidase) surrounded by fibrillin microfibrils. Appear poorly visible on H&E; stained by Weigert's resorcin-fuchsin or Verhoeff-Van Gieson (VVG — black). Present in skin, large artery walls (aortic media), lung parenchyma, ligamentum flavum. Elastin gene mutations → cutis laxa; fibrillin-1 mutations → Marfan syndrome.
Reticular fibres (type III collagen): Fine argyrophilic fibres forming delicate meshwork in lymphoid organs (spleen, lymph nodes), liver sinusoids, bone marrow, smooth muscle. Identified by silver impregnation (Gordon and Sweet's reticulin stain — black). Not visible on routine H&E.

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Types of Connective Tissue

Loose connective tissue (areolar): Most widely distributed; irregular arrangement of collagen I/III, elastic fibres, and abundant ground substance. Contains all CT cell types. Found in dermis (papillary layer), lamina propria of mucous membranes, adventitia of vessels, submucosa. Function: support, diffusion, immune surveillance.

Dense regular connective tissue: Densely packed parallel collagen type I bundles; few cells; little ground substance. Tendons (longitudinal collagen, tenocytes/tendinocytes in rows between fibres — stress-bearing design), ligaments, aponeuroses. On H&E, appears as parallel eosinophilic fibres with elongated nuclei.

Dense irregular connective tissue: Randomly interwoven collagen bundles; resists forces from multiple directions. Found in dermis (reticular layer), capsules of organs (liver capsule of Glisson, splenic capsule), sclera, periosteum.

Reticular connective tissue: Type III collagen meshwork; forms scaffolding for haematopoietic and immune cells. Liver, spleen, lymph nodes, bone marrow. Reticular cells (fibroblast-like) produce the fibres. Identified by silver stain.

Adipose tissue: Two types — white (WAT) and brown (BAT). WAT: insulation, energy storage, endocrine (leptin, adiponectin). BAT: non-shivering thermogenesis via UCP-1 (abundant in neonates; persists in adults in cervical, supraclavicular, and paravertebral regions detectable on FDG-PET). Lipoma: benign tumour of mature adipocytes; liposarcoma: malignant.

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Cartilage

Cartilage is a specialised connective tissue characterised by an ECM rich in type II collagen and glycosaminoglycans (chondroitin sulphate, keratan sulphate), which confer compressive resistance. Cartilage is avascular, alymphatic, and aneural; it receives nutrition by diffusion through the matrix. Repair is therefore slow and limited. Chondrocytes are the only resident cells, housed in spaces called lacunae. They are relatively inactive when surrounded by mature matrix.

Hyaline cartilage:

Most common type; bluish-white, glassy appearance grossly
Collagen type II (not visible on H&E because fibre diameter is smaller than wavelength of light — "masked")
Matrix: chondroitin sulphate, keratan sulphate, aggrecan, hyaluronic acid
Chondrocytes in lacunae, often in isogenous groups (2-4 cells derived from one progenitor by recent mitosis)
Perichondrium: outer fibrous layer (collagen I, fibroblasts) + inner chondrogenic layer (chondroblasts)
Locations: articular cartilage (no perichondrium), costal cartilage, trachea and bronchi (C-shaped rings), nasal septum, fetal skeleton
Undergoes endochondral ossification; articular cartilage may calcify (chondrocalcinosis) in CPPD disease

Elastic cartilage:

Contains abundant elastic fibres (Weigert's/VVG positive — black) in addition to type II collagen
More flexible than hyaline cartilage
Has a perichondrium
Locations: pinna of ear, epiglottis, auditory tube (Eustachian), apex of arytenoid cartilages

Fibrocartilage:

Contains type I collagen bundles (eosinophilic on H&E) interspersed with type II collagen matrix; no perichondrium
Chondrocytes in rows between collagen bundles
Provides both compressive and tensile strength
Locations: intervertebral discs (annulus fibrosus), pubic symphysis, menisci of the knee, insertion of tendons/ligaments into bone (enthesis), articular disc of TMJ

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Clinical Correlations

Ehlers-Danlos syndrome (EDS): Heterogeneous group of hereditary CT disorders affecting collagen biosynthesis or assembly. Classical EDS: COL5A1/2 mutations (collagen V); hypermobile EDS: unknown; kyphoscoliotic EDS: lysyl hydroxylase deficiency. Features: hyperextensible skin, joint hypermobility, fragile vessels, easy bruising.

Marfan syndrome: FBN1 mutation (fibrillin-1 of elastic fibre microfibrils); aortic root dilatation/dissection, ectopia lentis, tall stature with arachnodactyly.

Osteogenesis imperfecta (OI): Type I collagen mutations (COL1A1/2); brittle bones, blue sclerae (thin CT), hearing loss.

Osteoarthritis: Degradation of articular hyaline cartilage; loss of proteoglycans (matrix metalloproteinase activity), chondrocyte death, subchondral bone sclerosis, osteophyte formation, eburnation (ivory-like exposed bone).

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