Connective tissue histology
Connective tissue, cartilage, bone and joints: histology for FCPS Part 1
Connective tissue cells and fibres, the three types of cartilage, bone cells, ossification, fracture healing, joints and synovium for FCPS Part 1. Explains why cartilage heals poorly, which cell makes or removes bone, and how metabolic bone diseases look under the microscope.
Connective tissue
Connective tissue is cells scattered in an extracellular matrix of fibres and ground substance, all mostly made by fibroblasts.
- Fibroblasts secrete collagen, elastin, reticular fibres and the ground substance (glycosaminoglycans such as hyaluronic acid and chondroitin sulphate, and proteoglycans that bind water). Active fibroblasts have abundant rough ER; resting ones (fibrocytes) are thin and spindle-shaped. In wound infection, bacterial and neutrophil enzymes (collagenases, other metalloproteinases) destroy new collagen, delaying healing.
- Other cells: macrophages, mast cells (histamine, heparin), plasma cells, adipocytes.
| Fibre | Collagen type | Where |
|---|---|---|
| Collagen (thick, strong) | Type I | Bone, tendon, ligament, dermis, fibrocartilage, scars |
| Reticular (silver stain) | Type III | Framework of lymph nodes, spleen, liver, marrow; early granulation tissue |
| Elastic | Elastin on fibrillin microfibrils | Elastic arteries, lung, skin, elastic cartilage |
| Cartilage collagen | Type II | Hyaline and elastic cartilage, vitreous, nucleus pulposus |
| Basement membrane | Type IV | Basal lamina |
- Dense regular connective tissue (parallel fibres): tendons, ligaments. Dense irregular: dermis, capsules. Loose areolar: under epithelia.
- Brown fat (neonates, around the neck and between scapulae): multilocular cells with many mitochondria containing thermogenin (UCP-1), which uncouples oxidation from ATP synthesis to make heat. White fat is unilocular.
Wrapping layers of skeletal muscle
| Layer | Surrounds |
|---|---|
| Epimysium | Whole muscle |
| Perimysium | Each fascicle (bundle of fibres) |
| Endomysium | Each individual muscle fibre |
Arteries: elastic versus muscular
- Elastic arteries (aorta, pulmonary trunk, common carotid): media of many concentric fenestrated elastic lamellae that store energy in systole and recoil in diastole. The outer media is fed by vasa vasorum; syphilitic aortitis obliterates them, weakening the media and causing aneurysm of the ascending aorta.
- Muscular arteries (radial, coronary, femoral): media mainly smooth muscle, with distinct internal and external elastic laminae.
Cartilage
Cartilage is avascular and has no nerves or lymphatics; chondrocytes in lacunae are fed by diffusion through the matrix from the perichondrium or synovial fluid. That is why it heals poorly.
| Type | Collagen | Sites | Notes |
|---|---|---|---|
| Hyaline | Type II | Articular surfaces, costal cartilages, trachea and bronchi, thyroid and cricoid cartilages, nose, growth plates, fetal skeleton | Template for endochondral ossification; calcifies with age; articular cartilage has no perichondrium |
| Elastic | Type II plus elastic fibres | Auricle (pinna), epiglottis, external acoustic meatus, auditory tube, corniculate and cuneiform | Does not calcify |
| Fibrocartilage | Type I with some type II | Intervertebral disc (annulus fibrosus), pubic symphysis, menisci, TMJ disc, glenoid and acetabular labra | No perichondrium; resists tension and compression |
- Growth is interstitial (chondrocytes divide inside) and appositional (perichondrium adds new layers).
- Menisci are vascular only in their outer third (red zone, from the perimeniscal capillary plexus of the capsule); the inner two-thirds is avascular. A peripheral longitudinal tear close to the capsule can be repaired and heal; inner tears cannot. Preserving the meniscus reduces later osteoarthritis.
- Cartilage in airway walls defines bronchi; bronchioles have no cartilage (and terminal bronchioles no goblet cells).
Bone cells
| Cell | Origin | Function |
|---|---|---|
| Osteoblast | Mesenchymal stem cells (osteoprogenitors) | Makes osteoid (type I collagen); rich in rough ER and Golgi; alkaline phosphatase; expresses RANKL; has PTH receptors |
| Osteocyte | Osteoblast trapped in a lacuna | Senses load through canaliculi; makes sclerostin and FGF-23 |
| Osteoclast | Monocyte–macrophage lineage, multinucleated | Resorbs bone in Howship lacunae with a ruffled border; tartrate-resistant acid phosphatase; activated by RANKL, blocked by osteoprotegerin, calcitonin, bisphosphonates and denosumab |
- Compact bone: Haversian systems (osteons) with central canals, linked by Volkmann canals. Spongy bone: trabeculae with red marrow, no osteons.
- Woven bone (fracture callus, Paget disease) is disorganised and is replaced by lamellar bone.
- Periosteum: an outer fibrous layer and an inner cambium (osteogenic) layer containing osteoprogenitor cells. It is thick and active in children, so they heal quickly with abundant callus; excessive periosteal stripping during fixation causes delayed union.
Ossification and growth
| Type | Bones |
|---|---|
| Intramembranous (directly in mesenchyme) | Skull vault, facial bones, most of the clavicle and mandible |
| Endochondral (hyaline cartilage model) | Long bones, vertebrae, pelvis, skull base |
- Growth plate zones from the epiphysis: resting, proliferative, hypertrophic, calcified cartilage, ossification.
- Achondroplasia: an activating FGFR3 mutation brakes chondrocyte proliferation, giving short disorganised columns; short proximal limbs, large head with frontal bossing, normal trunk. Autosomal dominant, but about 80% are new mutations (older fathers).
- Rickets gives a widened, irregular growth plate.
Fracture healing
| Type | Conditions | How it heals |
|---|---|---|
| Secondary (indirect) | Some movement: casts, intramedullary nails, external fixators | Haematoma, inflammation, soft callus (fibrocartilage), hard callus (woven bone), remodelling to lamellar bone |
| Primary (direct) | Absolute stability and close contact: compression plating | Direct osteonal (Haversian) remodelling: cutting cones of osteoclasts cross the fracture, followed by osteoblasts; no external callus |
Callus around a rigid plate suggests instability. Healing is slowed by poor blood supply, infection, smoking, steroids, diabetes and malnutrition.
Joints
| Class | Type | Example |
|---|---|---|
| Fibrous | Suture, gomphosis, syndesmosis | Skull sutures, tooth socket, inferior tibiofibular joint |
| Primary cartilaginous (synchondrosis) | Hyaline cartilage, usually temporary | Epiphyseal plate, first sternocostal joint, spheno-occipital joint |
| Secondary cartilaginous (symphysis) | Hyaline-covered bone ends joined by fibrocartilage; midline | Pubic symphysis, intervertebral discs, manubriosternal joint |
| Synovial | Cavity, capsule, synovium | Knee, hip, shoulder |
- Synovium has no basement membrane, so cells and bacteria pass easily into the joint. Type A synoviocytes are macrophage-like (clear debris); type B synoviocytes are fibroblast-like and secrete hyaluronic acid (viscosity) and lubricin.
Metabolic bone disease
| Disease | Problem | Bloods | Histology |
|---|---|---|---|
| Osteoporosis | Too little bone, normally mineralised | Normal Ca, PO₄, ALP | Thin trabeculae; painless until fracture |
| Osteomalacia / rickets | Poor mineralisation (vitamin D lack) | Low or normal Ca, low PO₄, high ALP, high PTH, low 25-OH vitamin D | Wide seams of unmineralised osteoid; Looser zones; bone pain, proximal myopathy, waddling gait |
| Paget disease | Disorganised excess turnover | Very high ALP, normal Ca | Mosaic pattern of woven and lamellar bone |
| Hyperparathyroidism | Increased resorption | High Ca, low PO₄, high PTH | Osteitis fibrosa cystica |
| Osteopetrosis | Osteoclasts fail | Variable | Dense brittle bone, marrow failure |
Remember Blasts build (from mesenchyme), clasts chew (from monocytes).
Exam trap The pinna and epiglottis are elastic cartilage; the thyroid cartilage is hyaline.
Exam trap The first sternocostal joint is a synchondrosis (hyaline); the pubic symphysis is fibrocartilage.
How FCPS asks about this
- Primary cartilaginous joint: first sternocostal joint and epiphyseal plate (hyaline).
- Layer around a muscle fascicle: perimysium.
- Feature of the aorta versus a muscular artery: many concentric elastic lamellae in the media.
- Why a peripheral meniscal tear can heal: its outer third has a blood supply.
- Short limbs, frontal bossing, disorganised proliferative zone: activating FGFR3 mutation.
- Plated fracture healing without callus: direct osteonal remodelling (primary healing).
- Biopsy in osteomalacia: wide unmineralised osteoid seams; periosteal bone cells come from the cambium layer; hyaluronic acid from type B synoviocytes.
Test yourself on this topic
5 of the 29 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A transverse forearm fracture is fixed with a compression plate giving absolute stability and perfect bone contact. At 12 weeks the fracture line has faded on X-ray, but no external callus is visible. Which of the following describes how this fracture healed?
Answer: Direct osteonal remodelling across the gap
With absolute stability and close contact, bone heals by primary (direct) healing. Cutting cones of osteoclasts tunnel across the fracture, followed by osteoblasts laying down new osteons, so the cortex is remodelled directly without a cartilage stage or external callus. When there is some movement, as with casts or nails, healing is secondary, through haematoma, fibrocartilaginous soft callus and endochondral ossification, producing visible callus.
Primary vs secondary healing
- Absolute stability: primary healing
- Cutting cones cross the gap
- No callus on X-ray
- Movement: callus by endochondral route
Remember Rigid plate: no callus is the expected picture.
Exam trap Callus appearing around a rigid plate may signal instability rather than good healing.
Why the other options are wrong
- Endochondral ossification of soft callus This is secondary healing, which needs some movement and gives callus.
- Fibrous union replacing bone Fibrous union is a failure of healing.
- Intramembranous bridging callus Periosteal callus forms in relative stability, with visible callus.
- Osteoclast-only resorption of the ends Resorption without new bone would cause non-union.
A 5-year-old boy has had several fractures after minor falls, anaemia and hepatosplenomegaly. X-rays show uniformly dense, chalky bones with a 'bone-in-bone' appearance. His parents are first cousins. Which of the following defects most likely explains this?
Answer: Defective osteoclast acid secretion
This is autosomal recessive osteopetrosis. Osteoclasts cannot resorb bone, commonly because of a defect in carbonic anhydrase II or the proton pump and chloride channel needed to acidify the resorption pit. Bone accumulates and is dense but brittle, and it fills the marrow cavity, causing anaemia and extramedullary haematopoiesis with hepatosplenomegaly. Cranial nerve foramina may narrow, causing blindness and deafness.
Osteopetrosis
- Osteoclasts fail to resorb
- Often carbonic anhydrase II defect
- Dense but brittle bone
- Marrow filled: anaemia, hepatosplenomegaly
Remember Marble bone: too much, too brittle.
Exam trap Dense bone on X-ray does not mean strong bone; these bones fracture easily.
Why the other options are wrong
- Defective type I collagen Causes osteogenesis imperfecta, with thin fragile bones.
- Excess osteoblast proliferation Bone mass rises because resorption fails, not from osteoblast excess.
- Lack of vitamin D activation Causes rickets with poor mineralisation.
- Defective FGFR3 signalling Causes achondroplasia.
A 24-year-old footballer has a longitudinal tear of the medial meniscus seen at arthroscopy. The surgeon repairs it because it lies close to the capsule. Which of the following makes healing likely at this site?
Answer: Its outer third has a blood supply
Menisci are made of fibrocartilage, dense bundles of type I collagen with scattered chondrocytes. Only the peripheral 10–30% (the 'red zone'), attached to the capsule, receives blood vessels from the perimeniscal capillary plexus; the inner part is avascular and nourished by synovial fluid. Tears in the vascular outer zone can heal after repair, while inner 'white zone' tears usually do not and are trimmed.
Meniscus
- Fibrocartilage: type I collagen
- Outer third vascular (red zone)
- Inner part avascular (white zone)
- Repair peripheral tears
Remember Red zone heals; white zone does not.
Exam trap Removing the whole meniscus raises the risk of later osteoarthritis, so surgeons preserve as much as possible.
Why the other options are wrong
- It is made of elastic cartilage Menisci are fibrocartilage, not elastic cartilage.
- Its chondrocytes divide rapidly Meniscal chondrocytes divide slowly.
- Synovial fluid feeds the whole meniscus Synovial fluid feeds the inner zone, which heals poorly.
- It contains osteoprogenitor cells Menisci contain no bone-forming cells.
Why do injuries to articular (hyaline) cartilage heal poorly in adults?
Answer: Avascular; few dividing cells
Hyaline cartilage consists of chondrocytes in lacunae within a matrix of type II collagen and proteoglycans (aggrecan) that bind water, giving resistance to compression. It has no blood vessels, lymphatics or nerves; nutrients diffuse from synovial fluid or perichondrial vessels. Articular cartilage lacks perichondrium, so it cannot regenerate appositionally; defects that do not reach subchondral bone fail to heal, and deeper defects heal with fibrocartilage (type I collagen), which is mechanically inferior. Elastic cartilage (ear, epiglottis) has elastic fibres; fibrocartilage (intervertebral discs, menisci, pubic symphysis) has type I collagen.
Cartilage
- Hyaline: type II collagen; avascular; articular has no perichondrium
- Repairs with fibrocartilage (type I)
- Elastic: ear, epiglottis
- Fibrocartilage: disc, menisci, symphysis
Remember No vessels, no repair.
Why the other options are wrong
- Rich blood supply scars it It is avascular.
- It contains no collagen It contains type II collagen.
- Covered by perichondrium Articular cartilage lacks perichondrium.
- Replaced by osteoblasts Not the reason.
A newborn has short proximal limbs, a large head with frontal bossing and a normal-length trunk. Growth plate biopsy would show short, disorganised columns of proliferating chondrocytes. What is the underlying molecular defect?
Answer: Activating FGFR3 mutation
Achondroplasia is caused by a gain-of-function mutation in fibroblast growth factor receptor 3. FGFR3 normally restrains chondrocyte proliferation in the growth plate, so overactivity suppresses endochondral bone growth, mainly in the long bones. Intramembranous ossification of the skull vault and periosteal growth are unaffected, giving a relatively large head with normal intelligence. Most cases are new mutations, often linked to older paternal age.
Achondroplasia
- FGFR3 gain of function
- Suppresses chondrocyte proliferation
- Affects endochondral bone
- Skull vault (membranous) normal
Remember FGFR3 brakes the growth plate.
Exam trap Inheritance is autosomal dominant, but around 80% of cases are new mutations.
Why the other options are wrong
- Loss-of-function COL1A1 mutation Causes osteogenesis imperfecta with fragile bones.
- Fibrillin-1 mutation Causes Marfan syndrome with long limbs.
- Defective dystrophin Causes Duchenne muscular dystrophy.
- Carbonic anhydrase II deficiency Causes osteopetrosis with dense bones.
Where this sits in the CPSP syllabus
- Paper 1: General and special histology, Connective tissue, cartilage and bone
- Surgery & Allied, Paper 2: Histology for surgery, Connective tissue, cartilage and bone
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