What is the function of the chondroblasts in cartilage?
Secrete matrix which surrounds and entrapps chondroblasts in ‘lacunae’
What are lacunae entrapped chondroblasts called?
Chondrocytes
What does cartilage contain?
Chondroblasts/cytes
Type 1 collagen
Ground substance
No inorganic substances
What is the composition of the ground substance in cartilage?
Proteins Glycoproteins Glycosaminoglycans (GAGs) Hyaluronic acid Lipids Water
What are the two layers of the perichondrium?
What are these two layers composed of?
What types of cartilage possess a perichondrium?
Outer fibrous layer:
Dense Connective tissue
Inner chondrogenic (cellular) layer: Flattened Fibroblast-like cells that develop into chondrocytes
Perichondrium found surrounding Hyaline and Elastic cartilage
Explain the processes behind the growth of cartilage
Appositional Growth:
Fibroblast-like cells of perichondrium differentiate into chondroblasts which secrete matrix
Interstitial Growth:
Chondrocytes deeper in the cartilage dive forming isogenous groups. They then lay down matrix (this leads to the groups separation).
Describe how Cartilage is important in embryonic development and further growth of a child.
First appears during 5th week of embryo development
Embryo’s skeleton made of hyaline cartilage until replaced with bone.
Remnants of hyaline cartilage persist in growth plates and articular cartilage
What are the three major types of cartilage?
Hyaline cartilage
Elastic cartilage
Fibrocartilage
For hyaline cartilage:
What is the major type of collagen present?
What is its function?
Type 2 collagen present
Provide firm but flexible support
Allow movement of tissues
Where might hyaline cartilage be found?
Respiratory passageway
Articulating surfaces of long bones
Foetal skeleton
For elastic cartilage:
What is the major type of collagen present?
What is its function?
Type 2 collagen present
Provides extra flexibility and support (helps maintain shape) for structures
Where might elastic cartilage be found?
Auditory tubes
Pinna of the ear
Epiglottis
For fibrocartilage:
What is the major type of collagen present?
What is its function?
Type 1 collagen (in thick bundles)
Type 2 collagen as normal
Support and rigidity
Resistant to stretching and compression,
Can be weight bearing
Acts as a shock absorber and resists tearing
Where might fibrocartilage be found?
Intervertebral disks
Menisci
Pubic symphysis
Portions of the tendons
Describe the staining properties of cartilage matrix
Territorial matrix surrounding chondrocytes/isogenous groups stains more deeply with haemotoxylin than the inter-territorial matrix further from the chondrocytes
This is due to territorial matrix being more highly sulphated
What types of cartilage are avascular and how do they obtain nutrients?
Hyaline cartilage, elastic cartilage and fibrocartilage
Obtain nutrients via diffusion
What kind of joint is Fibrocartilage associated with?
Any joint where durability, resistance to compression and strength is needed
Why is elastic cartilage so named?
Matrix contains a large amount of elastic fibres
What is the clinical relevance of hyaline cartilage?
Hint: Ageing
Susceptible to degenerative aging process, can calcify/ossify in old age and disease
Joint pain can be the result of degraded articular cartilage erosion (osteoarthritis) or destruction of articular cartilage by granulating synovial membrane tissue (rheumatoid arthritis)
What is the clinical significance of fibrocartilage?
Tearing of menisci can occur
Rupture of annuls fibrosus (invertebral disk capsule)
Can lead to a slipped disk.
Does Elastic cartilage calcify in old age?
Nope
Bone is an example of what type of tissue?
Connective tissue
List the characteristics of bone
Hint: Nutrient supply? Composition? Physical characteristics? Types?
Can withstand compression, stress and deformation
Nutrient supplied through blood and lymph vessels
Innervated, susceptible to pain, particularly periosteum
Contains cells, fibres and ground substance like any other connective tissue
Two types:
Cancellous bone surrounded by compact/cortical bone
List the functions of bone
Support
Protection
Mineral storage
Haemopoesis
What are the structural characteristics unique to compact bone?
Concentric lamellae with central neurovascular canals (Haversian canals)
Interconnecting Volkmann’s canals between Haversian canals
Inner and outer circumferential lamellae
What is the key structural characteristic of cancellous bone?
How do these structures differ from the structure of compact bone?
Meshwork of trabeculae filled in with marrow
Trabeculae contain no osteons, only Interstitial/irregular lamellae w/osteocytes
What are the two types of bone marrow and their functions?
Red: Haemopoesis
Yellow: Contains adipose tissue, stores lipids
What is the inner surface of the marrow cavity of a bone lined with?
Endosteum - A thin layer of connective tissue
What is the organic material in bone comprised of?
Give %’s relative to overall bone mass
23% collagen
10% water
2% Non-collagen proteins
What are the two major inorganic constituents in bone?
Calcium carbonate
Calcium phosphate`
To what does bone owe its rigidity?
Interactions between inorganic salts and collagen
Why is bone flexible?
Due to the collagen content
How is calcium level in the blood controlled?
Parathyroid hormone prompts osteoclasts to reabsorb bone matrix leading to calcium in the blood.
Calcitonin is released when calcium levels in blood are high, this inhibits osteoclast activity and decreases bone reabsorption.
What are the three types of cells found in bone?
Osteogenitor/Osteoblasts
Osteocytes
Osteoclast
What is the function of Osteoblasts and what cell type do they differentiate from?
Synthesis of organic cell components, they produce osteoid
Derived from Osteogenitor cells
What are osteocytes and where are they found?
Osteoblasts that have become entombed in lacunae in bone.
What is the function of Osteocytes?
How Do Osteocytes gain nutrients?
Maintain bone
Osteocytes have slender cytoplasmic processes reaching out to adjacent osteocytes
These processes are entombed in cannaliculi (small vessels through bone matrix)
Processes connect via gap junctions so nutrients can be passed between osteocytes
What are Osteoclasts and what is their function?
How do they perform this function?
Large multinucleated cells derived from moncytes
Digest bone by releasing H+ ions and lysosomal enzymes to degrade bone matrix for reabsorption
What is the primary microstructure of bone and what is it’s significance in growth and repair?
Woven/Immature bone with collagen fibres arranged in random interwoven fashion
More cells less minerals
First bone to appear in development and repair, it’s later replaced by mature bone
What are the two types of secondary microstructure in bone?
Compact dense cortical bone
Sponge like cancellous medullary
What is an osteon and where might they be found?
Concentric lamellae of bone around a neurovascular canal (Haversian system)
Found in cortical bone
What can be found surrounding osteons?
Interstitial lamellae, remnants of incompletely digested osteons
How is a new osteon formed?
Hint: Cutting cone
Osteoclasts degrade and digest a tube of bone where the new osteon will be formed
Osteoblasts secrete osteoid (which is later calcified) behind the cutting surface to close up the space and form a new osteon
What process is bone continually undergoing?
What cells are involved and how?
Continuous remodelling and repair
Osteoclasts break down bone
Osteoblasts produce new bone in its place
What are the two types of bone formation and what tissues do they ossify?
Endochondral ossification - cartilage
Intramembranous ossification - mesenchyme or loose connective tissue
How does a bone progress from cartilage to fully ossified?
Starts with a hyaline cartilage model
Collar of periosteal bone appears on the shaft
Endochondral ossification begins at primary centre of diaphysis
Then secondary centres at the epiphysis are ossified
Growth in length occurs at cartilaginous epiphyiseal growth plates
Growth in diameter is by deposition of bone around periphery of shaft via intramembranous ossification
In terms of organic/inorganic material, what are the relative proportions present in bone?
65% inorganic
35% organic
Describe briefly how is bone formed via endochondral ossification.
Bone is formed from a cartilage model
Cartilage is reabsorbed and replaced by bone
Describe the structure of an epiphyseal growth plate and describe the processes occurring in each of the 5 layers
From Epiphysis to metaphysis layers are:
Zone of reserve cartilage
- No cellular proliferation or matrix production
Zone of Proliferation
- Cells divide and form columns
- Cells enlarge and secrete matrix
Zone of hypertrophy
- Cells enlarge greatly
- Matrix compressed into linear bands
Zone of calcified cartilage
- Enlarged cells begin to degenerate
- Matrix calcifies
Zone of resorption
- Small blood vessels and connective tissue invade region occupied by dying chondrocytes
- Calcified cartilage left as spicules between connective tissue and BVs
- Bone is laid down on these cartilage spicules
How does Osteogenesis imperfecta come about?
Rare heritable disorder
What is the underlying cause of osteogenesis imperfecta?
Rare genetic disorder
Defect in collagen synthesis by osteoblasts and fibroblasts
How is bone formed via intramembranous ossification?
Starts in highly vascularised loose connective tissues
Mesenchymal cells differentiate into osteoblasts surrounded by collagen and ground substance
Osteoblasts secrete uncalcified matrix (osteoid) which eventually calcifies
Osteoblasts become osteocytes when entombed in calcified osteoid
What issues does osteogenesis imperfecta present to an affected fetus?
Fractures in utero or during birth that are often fatal
What are the medico-legal considerations with osteogenesis imperfecta?
Possible confusion of multiple accidental fracture with deliberate injury
Where is vitamin D synthesised in the body?
In the skin under influence of sunlight
What is Vitamin D necessary for?
Proper absorption of Calcium and Phosphate by the small intestine
What is the result of Vitamin D deficiency in relation to bone?
Poorly mineralised, pliable matrix (decreased calcification of the osteoid)
Thus prevents osteoblasts becoming osteocytes
Affected bones unable to support body weight and will bend.
Common cause of Rickets or osteomalacia
What is the cause of Rickets?
Bone matrix fails to calcify properly (remains as osteoid)
What structures does Rickets affect?
Growing bones in children
What are the symptoms of rickets?
Epiphyseal growth plate distorted by body weight
Bone growth slow and deformed
Bones prone to fractures
Where does osteomalacia occur, what is it and what happens as a result?
Occurs in remodelling bone in adults
Deficient calcification decreases calcium levels in bone
Results in softening of the bone (increased fragility)
What are the common nutritional/behavioural causes of rickets and osteomalacia?
Inadequate intake of Vit. D, calcium or phosphate, possible in combination
Infants with low to no sun exposure may develop rickets due to Vit D deficiency that results
In less severe cases of osteogenesis imperfecta what are the symptoms seen?
Fragility of bones leading to frequent fractures
Bone deformities caused by fracture healing with poor alignment/weak callus
E.g. Bowed legs
What is Osteoporosis?
What are the two types of osteoporosis and how are they different?
Reduction in bone density to the point of high risk of fracture (fragile bones)
Type 1:
Most common
Occurs in post menopausal women
Due to increase in osteoclast number due to lack of oestrogen
Type 2:
Occurs in both sexes
Occurs after age 70 and reflects reduced osteoblast function
What is Osteoporosis?
What are the two types of osteoporosis and how are they different?
Reduction in bone density to the point of high risk of fracture (fragile bones)
Type 1:
Most common
Occurs in post menopausal women
Due to increase in osteoclast number due to lack of oestrogen
Type 2:
Occurs in both sexes
Occurs after age 70 and reflacts reduced osteoblast function
How does osteoporosis affect the bone structure?
Medullary canals enlarged due to trabecular breakdown
Gaps develop in the lamellae of cortical bone
What is achondroplasia a result of and what does this lead to?
Congenital, hereditary skeletal disorder that leads to:
Reduced endochondral ossification
Failure of proliferation and column formation in epiphyseal cartilage cells
Decreased cellular hypertrophy of cartilage cells
Decreased cartilage matrix production
What are the common risk factors for osteoporosis?
Age (from middle age onward bone becomes more porous)
Falling levels of oestrogen post menopause in women
Poor diet (lack of inorganic ions/insufficient calcium)
Insufficient exercise
Smoking (Hags with Fags)
What is the importance of osteoporosis as a risk factor for fractures in old age?
Elderly more likely to fall, osteoporosis increases risk of fracture
Why does achondroplasia not affect the skull bones?
Formed via intramembranous ossification, which is unaffected by achondroplasia
Explain in detail how achondroplasia effects long bone growth.
Epiphyseal growth plates are thin
There are few cells in the proliferation zone
Hypertrophic cartilage forms irregular columns
Zone of provisionally calcified cartilage is small and doesn’t provide adequate scaffolding for bone matrix deposition by metaphyseal osteoblasts
What is the effect of lack of growth hormone on a child’s bone development?
affects epiphyseal cartilage causing pituitary dwarfism.
What is the effect of excess growth hormone on a child’s bone development?
Excessive long bone growth leading to giantism
What is the effect of excess growth hormone on an adult’s bone development?
Due to lack of epiphyseal growth plates increase in length doesn’t occur.
However, periosteal growth of bones occurs, leading to thickening of the bones (acromegaly)
What is the primary effect of sex hormones on bone development?
Influences the appearance and development of ossification centres
How does precocious puberty affect bone development?
Retard bone growth due to premature closure of the epiphyseal growth plates
How do sex hormone deficiencies affect bone development?
Can cause epiphyseal growth plates to remain open for longer leading to taller stature.
How does thyroid hormone deficiency affect bone development
Causes cretinism, a condition in which bone development (as well as overall physical and mental development) is severely stunted.
What is the origin of cartilage?
Dervided from mesenchyme which differentiates into chondroblasts
After a break, a fracture in bone must be prepared, what are the 4 stages of bone repair?
Haematoma formation
Fibrocartilagenous callus formation
Bony callus formation
Bone remodelling
Describe the Haemotoma formation stage of bone fracture repair
Blood vessels in bone and periosteum break along with bone
Haematoma forms
Bone cells at fracture edge die
Swelling and inflammation occur
Phagocytic cells and osteoclasts remove damaged tissue
Haematoma is eventually cleared by macrophages
Describe the Fibrocartilagenous callus formation stage of bone fracture repair
New blood vessels infiltrate haematoma
Pro-callus of granulation tissue forms (rich in capillaries and fibroblasts)
Fibroblasts produce collagen fibres that span the break, some differentiate into chondroblasts that from a sleeve of hyaline cartilage that splints the bone
Osteoblasts from nearby endosteum and periosteum and multipotent marrow cells invade fracture site and begin reconstructing trabecular bone
Describe the bony callus formation stage of bone fracture repair
New Bone trabeculae begin to appear
Former fibrocartilagenous is converted to bony callus of cancellous bone via endochondral ossification
Intramembranous ossification also forms new cancellous bone in the area
This continue for ~2 months until a firm union is formed
Describe the bone remodelling stage of bone fracture repair
Cancellous bone callus is remodelled into compact bone
This continues for several months
Material bulging outside the bone, and inward into the medullary cavity is removed by osteoclasts
Shape of new bone the same as old bone.
Describe the appearance of someone who is achondroplasic.
Limbs are very short
Trunk is normal length
Vault of skull enlarged
Face small, with bridge of nose often flattened