LECTURE 5 (Bones Part II) Flashcards
Describe Bone remodelling in compact bone
Osteoclasts remove old bone and form small, tunnel-like cavities -> Tunnels are quickly invaded by OSTEOPROGENITOR CELLS from the ENDOSTEUM or PERIOSTEUM and sprouting loops of capillaries -> OSTEOBLASTS develop, line the wall of the tunnels, and begin to secrete OSTEOID in a cyclic manner, forming a new OSTEON with concentric lamellae of bone and trapped OSTEOCYTES
Describe the diagnostic technique where Tetracycline is used
1) Tetracycline is administered twice to patients with an interval of 11-14 days
2) A bone biopsy is performed
3) Bone is sectioned without decalcification and examined
What is the importance of Tetracycline?
Fluorescent molecules that binds newly deposited OSTEOID MATRIX during MINERALISATION with high affinity and specifically labels new bone under the UV microscope
[allows for measuring rate of BONE GROWTH -> diagnosis of bone disorders]
What does bone that is labelled with Tetracycline look like?
Bone formed while tetracycline was present appears as FLUORESCENT LAMELLAE and DISTANCE between the LABELED LAYERS is proportional to the RATE of bone appositional growth
Which diseases is Tetracycline useful in diagnosing?
- OSTEOMALACIA = mineralisation is impaired
- OSTEITIS FIBROSA CYSTICA = increased osteoclast activity results in removal of bone matrix and fibrous degeneration
Describe the two processes in which Bone development/Osteogenesis occurs
- INTRAMEMBRANOUS OSSIFICATION = osteoblasts differentiate directly from mesenchyme and begin secreting osteoid
- ENDOCHONDRAL OSSIFICATION = preexisting matrix of hyaline cartilage is eroded and invaded by osteoblasts which begin osteoid production
What happens before both processes of Osteogenesis?
In both processes, Woven bone is produced first and is soon replaced by stronger lamellar bone
Describe Osteogenesis Imperfecta
Also known as “Brittle bone disease”, are a group of congenital disorders in which osteoblasts produce deficient amounts of type I collagen or defective type I collagen due to genetic mutations
- All characterised by fragility of bones
- Fragility reflects the deficit in normal collagen which normally reinforces and adds a degree of resiliency to the mineralised bone matrix
Where does Intramembranous ossification take place?
Within condensed sheets “membranes” of embryonic mesenchymal tissue
Which bones are formed by intramembranous ossification?
- Skull & Jaws
- Scapula
- Clavicle
- Most flat bones
Describe what happens in Intramembranous Ossification
Condensed mesenchyme bone formation begins in OSSIFICATION CENTERS -> OSTEOPROGENITOR CELLS arise, proliferate and form incomplete layers of osteoblasts around a network of developing capillaries -> OSTEOID secreted by OSTEOBLASTS calcifies forming small irregular areas of woven bone with osteocytes in LACUNAE and CANALICULI -> Continued matrix secretion and calcification enlarges area & leads to fusion of neighbouring ossification centres
What happens when the Woven bone gradually gets replaced by Compact bone?
Compact bone encloses a region of cancellous bone with marrow and larger blood vessels
What happens to mesenchymal regions that do not undergo ossification?
Give rise to ENDOSTEUM and PERIOSTEUM of the new bone
Describe the bone formation in cranial flat bones
Lamellar bone formation predominates over BONE RESORPTION at both the internal and external surfaces -> Internal and external plates of compact bone arise while the central portion maintains its CANCELLOUS NATURE
[FONTANELLES or “soft spots” on the heads of newborns are areas of the skull where membranous tissue has not yet OSSIFIED]
Where does Endochrondal Ossification take place?
Within hyaline cartilage shaped as a small version or model of the bone to be formed
What is important in Endochrondal ossification?
- Forms most bones of the body
- Well studied in developing long bones
What are the steps of Endochrondal Ossification ?
1) Fetal hyaline cartilage model develops
2) Late in FIRST TRIMESTER, Cartilage calcifies and a PERIOSTEAL BONE COLLAR forms around DIAPHYSIS causing CHRONDOCYTE HYPERTROPHY in underlying cartilage
3) PRIMARY OSSIFICATION CENTRE forms in the DIAPHYSIS - Osteoid is deposited by new osteoblasts, undergoes calcification into woven bone and is remodelled as compact bone
4) SECONDARY OSSIFICATION CENTRE forms in EPIPHYSES
5) Bone replaces cartilage (except the articular cartilage and epiphyseal plates)
6) EPIPHYSEAL PLATES ossify and form EPIPHYSEAL LINES
What does Chrondocyte hypertrophy do?
Compresses the surrounding matrix and initiates its calcification by releasing OSTEOCALCIN and ALKALINE PHOSPHATASE
What happens when hypertrophic chrondocytes die?
They create empty spaces within the calcified matrix -> One or more blood vessels from the PERICHONDRIUM penetrate the bone collar bringing OSTEOPROGENITOR CELLS to the POROUS CENTRAL REGION -> Newly formed osteoblasts move into available spaces and produce woven bone -> Remnants of CALCIFIED CARTILAGE at this stage are BASOPHILIC and NEW BONE is ACIDOPHILIC
What happens when hypertrophic chrondocytes die?
They create empty spaces within the calcified matrix -> One or more blood vessels from the PERICHONDRIUM penetrate the bone collar bringing OSTEOPROGENITOR CELLS to the POROUS CENTRAL REGION -> Newly formed osteoblasts move into available spaces and produce woven bone -> Remnants of CALCIFIED CARTILAGE at this stage are BASOPHILIC and NEW BONE is ACIDOPHILIC
What are the two regions of cartilage?
- ARTICULAR CARTILAGE = within the joints between long bones which persist through adult life
- SPECIALLY ORGANISED EPIPHYSEAL CARTILAGE = connects each epiphysis to the diaphysis and allows longitudinal bone growth
What is the function of epiphyseal cartilage?
Responsible for the growth in bone length and disappears upon completion of bone development in adulthood (epiphyseal closure)
What does the epiphyseal growth plate show?
Distinct regions of cellular activity
What are the different locations and zones of Epiphyseal activity?
- ZONE OF RESERVE (OR RESTING) CARTILAGE = composed of typical hyaline cartilage
- PROLIFERATIVE ZONE
- ZONE OF HYPERTROPHY
- ZONE OF CALCIFIED CARTILAGE
- ZONE OF OSSIFICATION
What happens in the Proliferative zone?
Cartilage cells divide repeatedly, enlarge and secrete more type II collagen and proteoglycans and become organised into columns parallel to the long axis of the bone
What is the Zone of hypertrophy?
Contain swollen terminally differentiated chrondocytes which compress the matrix into aligned spicules and stiffen it by secretion of type X collagen
What happens in the Zone of calcified cartilage?
Chrondocytes about to undergo apoptosis release matrix vesicles and OSTEOCALCIN to begin matrix calcification by the formation of HYDROXYAPATITE CRYSTALS
What happens in the Zone of Ossification?
- Bone tissue first appears
- Capillaries & Osteoprogenitor cells invade the vacant chrondocytic lacunae which merge to form the initial marrow cavity
- Osteoblasts settle in a layer over the spicules of calcified cartilage -> Woven bone
- Woven bone is remodelled as lamellar bone
What happens in the growth in the circumference of long bones?
Occurs through the activity of OSTEOBLASTS developing from OSTEOPROGENITOR CELLS in the periosteum by a process of APPOSITIONAL GROWTH. Bones increase in diameter as new bone tissue is added.
Describe Rickets
A disease caused by calcium deficiency or failure to produce vitamin D in which the bone matrix does not calcify normally and the epiphyseal plate can become distorted by the normal strains of body weight and muscular activity
[vitamin D is important for the absorption of Ca2+ by cells of the small intestine]
SYMPTOMS:
- slow growth of bones
- deformed bones
In adults what can Calcium deficiency result in?
OSTEOMALACIA characterised by deficient calcification of recently formed bone and partial decalcification of already calcified matrix
What does bone growth involve?
The continuous resorption of bone tissue formed earlier and the simultaneous laying down of new bone at a rate exceeding that of bone removal
What is bone modelling?
In adults when the skeleton is renewed continuously in a process that involves the coordinated, localised cellular actives for bone resorption and bone formation. It maintains the bone’s general shape while increasing its mass.
Why does the bone have an excellent capacity for repair?
It is very well vascularised
Describe the steps of bone fracture repair
1) Blood vessels torn within the fracture release blood that clots to produce a LARGE FRACTURE HEMATOMA
2) Hematoma is gradually removed by MACROPHAGES and replaced by PROCALLUS TISSUE. If torn by the break, the PERIOSTEUM re-establishes its continuity over this tissue
3) PROCALLUS is invaded by regenerating blood vessels and proliferating osteoblasts -> Fibrocartilage is replaced by woven bone -> Woven bone is remodelled as compact and cancellous bone
What do bone fractures do to blood vessels?
Bone fractures disrupt blood vessels causing bone cells near the break to die
What is the importance of Calcium in bones?
The skeleton serves as a CALCIUM RESERVOIR containing calcium in HYDROXYAPATITE CRYSTALS. Concentration of calcium in blood & tissues is stable because of continuous interchange between blood calcium and bone calcium -> Ca2+ used in enzymes, exocytosis etc.
What are the properties of Ca2+ mobilisation?
- Principal mechanism for raising blood calcium levels is the mobilisation of ions from hydroxyapatite to interstitial fluid (primary in cancellous bone)
- Ca2+ regulated by PARACRINE INTERACTIONS
What are the two polypeptide hormones that target bone cells to influence calcium homeostasis?
- PARATHYROID HORMONE (PTH)
- CALCITONIN
What are the properties of Parathyroid Hormone (PTH)?
- From parathyroid gland
- Raises low blood calcium levels by stimulating osteoclasts and osteocytes to resorb bone matrix & release Ca2+
- Effect on osteoclasts is INDIRECT
- PTH receptors occur on osteoblasts -> respond by secreting RANKL and other paracrine factors that stimulate osteoclast formation and activity
What are the properties of Calcitonin?
- Produced by Thyroid gland
- Decreases elevated blood calcium levels by opposing the effects of PTH in bone
- Hormone directly targets osteoclasts to slow matrix resorption and bone turnover
Describe the effects of Growth Hormone
Synthesised by the PITUITARY GLAND -> Stimulates the liver to produce insulin-like growth factor 1 (IGF) which has a growth-promoting effect on epiphyseal cartilage -> Lack of GH causes PITUITARY DWARFISM & excess of GH causes GIGANTISM
What happens to adults when given growth hormones
Adult bones CANNOT increase in length even with excess growth factors because they lack EPIPHYSEAL CARTILAGE but can increase in width by PERIOSTEAL GROWTH. Increase in GH also causes ACROMEGALY (a disease in which the bones become very thick)
What happens in Rheumatoid Arthritis?
Chronic inflammation of the synovial membrane causes thickening of this connective tissue and stimulates the macrophages to release collagenases and other hydrolytic enzymes.
What are the stages of Rheumatoid Arthritis?
1) Body mistakenly attacks its own joint tissue
2) Body makes the antibodies and the joints start swelling up
3) Joints start becoming bent and deformed, fingers become crooked and mis-shaped joints press on nerves and cause nerve pain
4) If left untreated, no joint remains -> joint is fused
What are the properties of Joints?
- Held together firmly by other connective tissues
- Type of joint determines the degree of movement between the bones (limited or no movement)
- Classified as SYNARTHROSES
- Subdivided into fibrous and cartilaginous joints
What are the major types of joints/synarthroses?
- SYNOSTOSES
- SYNDESMOSES
- SYMPHYSES
What are Synostoses?
Link bones to other bones and allow no movement
[in adults synostoses unite the skull bones but in children and young adults are held together by SUTURES]
What are Syndesmoses?
Join bones by dense connective tissue only
What are Symphyses?
Have a thick pad of fibrocartilage between the thin articular cartilage covering the ends of the bones. Occur in the midline of the body.
What are intervertebral discs?
Large symphyses between the articular surfaces of successive bony vertebral bodies
What are the properties of Intervertebral discs?
- Cushion the bones and facilitate limited movements of the vertebral column
- Disc composed of fibrocartilage and surrounded by ANNULUS FIBROSUS
- NUCLEUS PULPOSUS in centre of annulus is a proteoglycan-rich, gel-like body which acts as a shock absorber
Describe a Slipped/Herniated disc
Caused by collagen loss or other degenerative changes in the annulus fibrosus & accompanied by displacement of the nucleus pulposus. Most frequently occurs on the POSTERIOR REGION of the intervertebral disc where there are fewer collagen bundles
COMPLICATIONS:
- Disc dislocates/shifts from normal position
- If moves towards NERVE PLEXUSES, it can compress nerves -> severe pain & neurologic disturbances
Describe a Slipped/Herniated disc
Caused by collagen loss or other degenerative changes in the annulus fibrosus & accompanied by displacement of the nucleus pulposus. Most frequently occurs on the POSTERIOR REGION of the intervertebral disc where there are fewer collagen bundles
COMPLICATIONS:
- Disc dislocates/shifts from normal position
- If moves towards NERVE PLEXUSES, it can compress nerves -> severe pain & neurologic disturbances
What are Diarthroses?
Joints that allow free movement of the attached bones (e.g knuckles, knees and elbows)
What are the properties of Diarthroses?
- Unite long bones & allow great mobility
- Maintain proper alignment of the bones
- Capsule encloses a sealed JOINT CAVITY containing SYNOVIAL FLUID
- Joint cavity is lined by SYNOVIAL MEMBRANE
Describe Diarthrotic joints
- Prominent regions with dense connective tissue or fat
- Superficial regions of tissue as well VASCULARISED with many POROUS CAPILLARIES
What are the specialised cells found in synovial membrane and their functions?
- MACROPHAGE-LIKE SYNOVIAL CELLS/TYPE A CELLS = remove wear and tear debris and regulate inflammatory events
- FIBROBLASTIC SYNOVIAL CELLS/TYPE B CELLS = produce hyaluronan and proteoglycans which is used to form synovial fluid
What are the functions of Synovial fluid?
- Lubricates the joint
- Reduces friction on all internal surfaces
- Supplies nutrients and oxygen to the articular cartilage
What happens in the bones of elderly?
- Osteogenic property of autologous bone graft decreases
- Osteoconductive property is compromised
