G&D- Bones, Growth Flashcards
(167 cards)
1
Q
What is bone?
A
specialised connective tissue.
= living cells embedded in a mineralised extracellular matrix (ECM).
2
Q
Name 3 bone types
A
1- trabecular
2- cortical
3- woven
3
Q
Composition in % of bone
A
30% organic material (majority is collagen),
45% inorganic hydroxyapatite (HA)
4
Q
What is HA
A
hydrated crystalline material of calcium and phosphate.
Hydroxyapatite provides strength.
5
Q
HA content: in % in different connective tissues
A
Bone approx 45%
cementum 55%
dentine (70%),
enamel (90%)
6
Q
What is in the bone matrix?
A
Collagen fibres (95% type 1, 5% type 5) Carbonated hydroxyapatite crystals.
Proteins (unique to calcified tissue) e.g. osteocalcin
7
Q
Bone function- support
A
Mineralised when fully developed.
Supports/protects internal organs.
Allows movement
8
Q
Bone function- metabolic
A
Haematopoiesis: bone marrow produces blood cells
Calcium homeostasis
9
Q
Serum Ca2+ levels maintained by interplay between :
3
A
> intestinal absorption,
renal excretion
skeletal mobilisation or uptake.
10
Q
What is cortical bone?
A
Cortical/Compact/laminar:-
approx 80% of skeleton,
dense, very strong, forms the outer layer of all bones.
11
Q
What is trabecular bone?
A
porous meshwork of bone.
Makes up approx. 20% of the skeleton, mainly in axial skeleton.
Bone strength also determined by the trabecular microstructure-can change in disease e.g. osteoporosis.
12
Q
What is woven bone?
A
forms quickly during periods of repair or rapid growth.
..remodelled into lamellar bone.
13
Q
What is the periosteum?
A
lines the outer surface of cortical bone
14
Q
How is bone a dynamic tissue?
Constant remodelling!
A
Changes all the time to
- > meet stress loads
- > release Ca++ and phosphate if required
- Max strength, min weight
15
Q
Cell-types in bone (5)
A
Osteoclast Osteoblast Osteocyte Bone lining cells Osteoprogenitor cells (stromal)
16
Q
What are Osteoclasts?
A
Large multinuceated cells. Bone resorbing cells
17
Q
What are osteoblasts?
A
Bone forming cells
18
Q
What are osteocytes?
A
Originate from osteoblasts.
- have become embeded in bone matrix.
- Involved in sensing mechnaical loads and Ca homeostsis
19
Q
What are bone lining cells?
A
Originate from osteoblasts
- line quiescent periosteoal and endosteal surfaces of bone
20
Q
What are osteoprogenitor cells (stromal cells)
A
Precursors of osteoblastic lineage
21
Q
How many microscopic sites is remodelling estimated to be occuring at, at any one time
A
1-2 million
22
Q
Why does bone remodelling occur? (i.e. bone is constantly being destroyed and reformed).
A
- Release calcium
- Alter architecture of cancellous bone to meet new stresses
23
Q
What is the resorption phase/ how long
A
bone ECM destroyed and removed.
This phase takes approx 3 weeks/remodelling site.
24
Q
What is the bone formation phase and how long
A
New ECM is formed and mineralised
-this phase takes 3-4 months/remodelling site.
25
Mechanism of bone remodelling
- Osteoclast precursors recruited to remodelling site
- Mature to osteoclasts
- Bone lining cells erode a little ECM, then leave the remodelling site
- Osteoclasts bind to the ECM exposed by BLCs, they digest the bone matrix with enzyme
- Resorption pit formed
- Osteoclasts apoptose
- Osteoblast precursors recruited
- Mature into Osteoblasts
- New ECM made by Ob
- New bone surface becomes covered in bone lining cells
26
When might bone formation be needed?
- during formation of the skeleton
- during fracture repair
- during tooth socket healing after extraction
27
NAme 2 types of bone formation
1- intramembranous ossification (IMO)
2- endochondral ossification (ECO)
28
What is Intramembranous ossification?
Bone is formed directly from condensed mesenchyme/ ectomesenchyme
29
What is endochondral ossification?
A cartilaginous precursor of the bone is formed and replaced by bone as it grows
30
Where does IMO occur?
ONLY in:
- Neurocranium- bone enclosing the skull
- Viscerocranium- facial bones of skull
- Clavicle
31
Where does ECO occur?
More common..
ALL bones except outside the skull...
- including the basicranium (chondrocranium)
- Except the clavicle
32
How does IMO occur?
- Mesenchymal stem cells condense and Differentiate into osteoblasts
- Secrete ECM (osteoid) in long strands
- Obs lay down bone mineral on the strands of Osteoid
- Consecutive growth rings of Osteoid (lamella) added on to increase thickness
- Further bone growth by cycles of osteoid secretion and mineralisation (appositional growth)
- Multiple trabecular within the developing bone contact one another to form a lattice structure
33
Name for bone containing lattice structures
Primary cancellous (trabecular) bones
34
Name for bones that completely fill in wtih mineralised osteoid
Compact (cortical)bone!
35
What is Cleidocranial dysostosis
a rare genetic disorder that interferes with intramembranous ossification (skeletal dysplasia)
Autosomal dominant-defect in the RUNX2 gene
36
Clinical symtpoms of cleidocranial dystosis
Neurocranium underdeveloped
Viscerocranium underdeveloped with severe dental malocclusion, delayed formation
Large head and frontal bossing
Clavicles reduced or absent-characteristic feature
37
How many affected by cleidocranial dystosis?
approx. 1 in 1million
38
hree phase processes in ECO
1) Miniature cartilage replica formed by diff of mesenchyman/ectomesen. cells -> into chondroblasts -> which mature into chondrocytes
2) Cartilage grows in a specific direction (interstitial and appositional growth)
3) cartilage is converted into bone!
39
What is the Epiphyseal growth plate?
Hyaline cartilage plate in the metaphysis at each end of a long bone
40
What are the 2 zones of epiphyseal growth plate?
- Proliferation zone
- Hypertrophic zone
- Cartilage / bone interface
41
What is Achondroplasia?
recessive genetic condition that affects bone formation via ECO.
Autosomal dominant.
Incidence is 1 in 20,000.
Most common form of dwarfism.
42
What genetic defect results in achondroplasia?
Genetic defect is in the gene for FGFR-3
a membrane receptor that is important in the response of chondrocytes to..
growth factor (FGF-18) during development of the cartilage ‘template’.
43
Name 5 methods of assessing growth timing/rate
1. measurement of change in height
2. secondary sexual characteristics
3. hand-wrist radiographs
4. Radiographic assessment of cervical spine maturation
5. Average growth increments
44
What is PHV?
Peak height velocity
- Maximum rate of growth
- During puberty, growth velocity curve rises to a max. and begins to fall again
45
What are the 4 major tissue systems plotted on Scammons growth curve-
General
Genital
Lymphoid
Neural
46
How are hand-wrist radiographs used?
Large number of centres of ossification present in the relatively small area
47
What is the atlas technique?
Ulnar sesamoid bone ossifies at the start of the pubertal growth spurt.
- Median bone maturity stage for each chronological age and sex was identified/ can compare/ use as a reference
48
What is a cephalogram?
A cephalogram is an X-ray of the craniofacial area. A cephalometric analysis could be used as means for measuring growth in children.
- 3 cervical vertebrae
49
What craniofacial changes occur during puberty/growth
Facial dimensions increase...
- Vertical changes are most prominent
- Antero-posterior changes are less prominent
50
What soft tissue changes happen during growth
Greatest changes here rather than in hard tissues...
- Lip incompetency... decreases with age
- Lower lip grows more
- LFH= lower facial height increase
51
Name 3 endocrine hormones involved in the control of growth
```
Growth hormone
Oestrogen
Androgen
Glucocorticoids
Insulin
Insulin-growth factor 1
Thyroid
```
52
What is the human growth hormone?
Peptide hormone that stimulates growth, cell reproduction and cell regeneration in humans...
53
What gland secretes GH
```
Pituitary gland (In brain)
- Regulated by neurosecretory nuclei of the hypothalamus
```
54
What is Gigantism
Occurs during childhood
| - Excessive GH before growth plate closure...
55
What is acromegaly
middle-aged people
3 per million
Excessive GH due to benign tumours on pituitary?
56
What affect does Oestrogen have on GH?
Increases GH secretion
- Induces epiphyseal plate closure
- Direct and indirect effects
57
What role do Androgens have on Growth?
Play a role in male traits and reproductive activity
| e.g. Testosterone
58
Androgen affect on bones...
Radial bone growth-> bones get fatter
... Make growth plate increase in size
- Androgen receptors in bone
- Can be converted to oestrogen
59
Why are males bigger?
Less oestrogen!
Oestrogen also inhibits condylar growth-> masculine contour of the mandibular angle
60
GH affect on muscle growth?
GH acts on IGF1 for myofibril proliferation.
Paracrine IGF1 has a role in load-induced hypertrophy.
61
GH as a performance-enhancing drug(3)
1- positive effect on CT strength
2- Reduce recovery time (anticatabolic)
3- Increased VO2 max
62
What do glucocorticoids do?
Increase GH secretion.
Affects SST and GHRH release.
Chronic Glucocorticoid exposure reduces GH release (leasds to glucose intolerance)
63
Insulin involvement in growth due to GH= diabetogenic...
GH promotes gluconeogenesis (making of glucose), glucogenolysis (break down) and lipolysis... GH is therefore diabetogenic (causes diabetes)
Insulin is released to compensate for this.
Long term.. can lead to insulin resistance
64
Insulin as a IGF1 homologue
Can cause insulinopenia (reduction in insulin levels)... reduces children's growth
65
What effect does thyroid hormone have on growth
- Increases linear growth
T3 affects chondrocytes and osteoblasts in growth plate
- Drives IGF1 synthesis pre-pubertal
- Stimulates GH synthesis
Hypothyroidism= reduces adult height
66
What is IGF1???
Insulin growth factor 1
- Similar molecular struc to insulin
- childhood growth
- Anabolic effects in adults
- Tx for child growth failrure
- Produce in liver
- Production is stimulated by GH, can be retarded by undernutrition, GH intensity, lack of GH receptors
- Produced throughout life
67
What is calcium?
1kg in the body.
99% in bone
Blood and ECF total = 2mM = 60% Ca2+
- Involved in intracellular signalling
68
What is trousseau's sign
Reduced blood flow.
- Neuromuscular irritability
- Hypocalcaemia causes Na+ influx (sustained muscle contraction, high AP rate)
69
How much calcium needed in mg
Adults= 1300mg (or 700?)
70
Food sources of calcium
milk, oily fish, bread, broccolli
71
Processes by which small intestine absorbs calcium from diet
Transcellular: low intake, active
Paracellular: high intake, passive
72
What hormone does thyroid gland release (involved in calcium homeostasis)
Calcitonin
| parafollicular cells in thyroid
73
What does Calcitonin do?
Increases bone mineralisation.
Decreases Ca2+ reabsorption in kidneys.
Overall: causes a decrease in Plasma Ca2+ levels
74
What hormone does parathyroid gland release (involved in calcium homeostasis)
Parathyroid hormone
75
Parathyroid hormone functions
- Causes osteolysis (bone breakdown and release of Ca)
- Increases Ca2+ reabsorption in kidneys
- Increase in Ca2+ absorption from gut?? (diet)
Overall: causes a INcrease in Plasma Ca2+ levels
76
What does the 1,2,4-dihydroxy-cholecalciferol hormone do?
- Increases Ca2+ reabsorption in kidneys
- Increase in Ca2+ absorption from gut?? (diet)
Overall: causes a INcrease in Plasma Ca2+ levels
77
What is the name for Vit. D?
Calcitrol
78
Vit. D in calcium homeostasis
Crucial for uptake!
Vit. D allows SI absorption of calcium by:
- Upregulates carriers/ Ca pumps (transcellular)
- Makes gap junctions more porous to Ca
79
What is rickets?
Skeletal disorder caused by lack of vit.D, calcium or phosphate.
Weak, stunted bones/growth/deformities
Growth plates have vit.D receptors
80
Vit. D effects on developing teeth-
```
6-24 months of age
Enamel hypoplasia
Enlarged pulp horns
Delayed eruption
Caries risk
Prevention: take vit.D and fluoride supplements
```
81
How does bone turnover occur...
In low levels of vit.D...
- Ob release RANK ligand
- Osteoclasts differentiation
- Oc activation
- Resorption of bone
- Calcium release
82
Name some Non-skeletal roles of calcium...
```
Cancer
Autoimmune disease
Schizophrenia
Depression
Diabetes
muscle strength
```
83
What is osteomalacia?
Closed growth plates
- Low density bones
- Lack of remineralisation
- Pathological amount of callus matrix
- Pseudofractures, including in mandible
- Bone pain
- Muscle weakness
- Periodontitis
84
What is osteoporosis?
Fragile, weak bones... resulting in fracture?
More spongy, porous,..
Loss in density
85
Pathogenesis of osteoporosis:
- Reduced uptake of dietary calcium
- Imbalance of bone turnover
- Reduced bone mineral density
86
Oestrogen affect on bone?
Reduced inhibition of osteoclasts...
- Inhibits bone breakdown, resorption /reabsorption of Ca
- Levels of oestrogen fall after menopause leading to more bone resorption ... get more fragile...
87
Name 2 drugs used to Tx of osteoporosis
1- Adcal
| 2- Alendronic acid
88
what is Adcal
Calcium carbonate with vitD
89
What is Alendronic acid
Bisphosphonate drug which inhibits osteoclasts and stops over-activation of them...
(stops breakdown!)
90
2 mechanisms of bone growth
1- Interstitial growth
| 2- Direct growth
91
What is interstitial growth?
soft tissues- combination of hyperplasia (increase in number of cells) and hypertrophy (increase in size of cells).
In the craniofacial skeleton, it occurs in cartilages, synchondroses and sutures.
92
Examples of interstitial growth
Endochondral ossification is the conversion of cartilage.
Intramembranous ossification occurs only in the embryo and is the direct transformation of mesenchymal cells into osteoblasts.
93
What is direct bone growth
surface apposition (bone being added on the surface by osteoblasts) and resorption (bone being removed by osteoclasts).
94
What is the primary mechanism that shapes the craniofacial skeleton?
Direct growth.
In fully formed bone, growth activity can only occur in the periosteum - periosteal surface remodelling (including sutural deposition)
The processes of apposition and resorption constitute remodelling.
95
Name 3 theories of control mechanisms of craniofacial growth
1- Sutural directed growth in sutures
2- Cartilage directed growth theory (genetically determined)
3- Functional matrix theory
96
What is the Sutural directed growth in sutures theory
sutures in bones are growth centres.
| There is expression of growth at these sites which causes changes in shape.
97
How is growth of cranial vault determined?
NOT determined by sutures but by pressure from growing neural tissues.
98
What is the Cartilage directed growth theory?
```
Growing cartilage is replaced by bone...
Cartilage growth sites:
- Spheno-occipital and spheno-ethmoidal synchondroses
- Nasal septum
- Mandibular condyle
```
99
What are synchondroses?
@ cranial base...
- Possible cartilage growth sites
- Immovable joints between bones, bound by layer of cartilage
2 epiphyseal cartilages placed back to back (with a common central zone of resting cells)
100
What is the functional matrix theory?
- Bone growth in response to growth of surrounding tissues
| - Craniofacial growth as a response to functional needs that is mediated by tissue growth
101
What are the 2 matrices in the functional matrix theory:
1- Periosteal matrix: muscles, nerves, glands, teeth
2- Capsular matrix: neurocranial, orbital and pharyngeal fossae
102
Examples of functional matrix
Coronoid process only grows if subject to functional forces from masseter and medial pterygoid muscles
Aleolar bone loss if teeth loss
103
At birth, what % of body length is head
25%
104
At adulthood, what % of body length is head
12%
105
Age 1, what % of total wt is the brain
50%
106
Age 3, what % of total wt is the brain
75%
107
Age 7, what % of total wt is the brain
90%
108
Age 11, what % of total wt is the brain
FULL
109
What are sutures
Formed in membranous bone without cartilagenous precursors
- Secondary growth centres
- Periosteal growth activity
- Fast rate of growth
- Begin to fuse by age 7
- Fused by 17
110
Functional matrix theory- cranial vault perspective
Sutures allow expansion for brain.
111
What separates the anterior/posterior regions of the cranial base
Spheno-occipital synchondrosis
112
Anterior region - cranial base
spheno- ETHMOIDAL synchrondrosis
- Neural pattern of growth
Stable by age 8
Active until age 18
113
Posterior region
Spheno OCCIPITAL synchondrosis
Somatic pattern of growth
Active until age 16
114
What happens to the facial bones from 0-12 years
Enlargement, make space to accommodate airway and masticatory growth/function
115
What happens 12-18yrs, puberty to face:
- Forward growth of jaws
- Forward elongation of nose
- Backward shift of orbits
- Posterior movement of zygoma
- Posterior extension of dental arches in tuberosity of maxilla
116
How does growth of Maxilla occur?
-Downwards and forwards
Surface and sutural deposition
Sutures respond to separating forces caused by soft tissue growth.
- Bone added at sutures and tuberosity areas.
- Floor of nose is resorbing
- Bone being added to FOM
117
Growth of mandible?
- Grows in length and upwards
Condylar head is remodelled
Ramus is remodelled
More height growth than length.
Resorption and apposition at condylar head.
- Cartilage replacement in 2ndary growth cartilage
Resorption from ANTERIOR surface.
Deposition on POST. surface.
118
What is the condyle made of?
Condylar cartilage (not true cartilage)
- Resembles epiphyseal cartilage of long bone
119
What happens to cells of proliferative zone in condyle
They differentiate into chondroblasts, once this happens,
Chondrogenesis is appositional (NOT organised into parallel columns)
120
What are jaw rotations?
50% true rotation
| - Rotation masked by surface apposition and resorption
121
What 2 types of rotation occur and waht %
25% Matrix rotation (around condyle)
75% Intra-matrix rotation; within body of mandible
122
Mandible rotation?
M. plane decreases by 2-4 degrees
| - Forward 4 out 5 cases
123
Maxilla rotation?
Forward rotation by 3 degrees
124
What might cause a long face?
```
Backwards rotation.
- Matrix rotation
- Open bite
- Incisors thrust forward...
Class 2?
```
125
What might cause a short face?
```
Forwards roation
- Short ant. face height
- Forward rotation of mandible...
Deep bite
- Crowded incisors
```
126
What is adenoidal facies?
Posterior nasal obstruction
Increased face height
- increased lower and total face height
- narrow upper arches
- retroclined incisors
Difficulty with nasal breathing...
127
2 phases of facial soft tissue growth during puberty:
1- mainly growth of midface downwards
| 2- significant growth of face downwards
128
Craniofacial anomaly classification (2)
3% of births
- Embryological
| - Developmental (worsen with growth?)
129
Name 2 embryological craniofacial anomalies
1- Facial clefts
| 2- First arch anomalies
130
What is cleft-palate
1 in 680 births
- Hearing and speech difficulties
- Dental anomalies
131
What are mid-face clefts
HPE- cephalic disorder, the prosencephalon fails to develop into 2 hemespheres...
- Midline features are affected
132
What is hemi-facial microsomia?
| first arch anomaly
Early mixed dentition.
1 in 4000
Interrupted blood supply to branchial arch.
Restricted facial development...
133
What is treacher collins
| first arch anomaly
1 in 50,000
Autosomal dominant.
Affects mesenchymal flow in 1st/2nd p arches.
- Hypoplastic maxilla/mand.
- Ear anomalies
- Cleft palate
134
What is craniosynostoses?
Premature fusion of 1+ fibrous sutures resulting in distortion of cranial development and facial features
135
Examples of craniosynostoses
- Crouzon's syndrome
- Apert's syndrome
- Achondroplasia
136
Prevalence of craniosynostoses
1 in 2000
137
What is Crouzon's syndrome
```
1 in 25,000
Autosomal dominant
Premature fusion of sutures
- Raised ICP
- Facial appearance...
- Restricted mid-face
- High arched palate
- Speech diff
Class 3?
```
138
What is Apert's syndrome?
1 in 50,000
- similar to Crouzon
- united fingers?
139
What is Achondroplasia?
1 in 15,000 and 1 in 40,000
ADominant
Abnormality in cartilage formation, causing shortening of limbs (dwarf)
140
What does this embryonic germ layer make: ectoderm
Epidermis, glands, enamel
141
What does this embryonic germ layer make: Endoderm
Gut lining
| Glands
142
What does this embryonic germ layer make: Ventral mesoderm
Blood vessels and cells
143
What does this embryonic germ layer make: dorsal mesoderm/ neural crest
Muscle, CT, bone, sensory nerves
144
What does this embryonic germ layer make: Neural tube
CNS and motor nerves
145
What does each pharyngeal arch contain
- Artery, vein, cranial nerve
- Skeletal element
- Muscle (migrates into each arch)
146
What nerves innverates arch 1
Trigeminal (V), third division
147
What nerves innverates arch 2
Facial (VII)
148
What nerves innverates arch 3
Glossopharyngeal (IX)
149
What nerves innverates arch 4
Vagus (X)
150
What muscles are in Arch 1
muscles of mastication
some suprahyoids
tensor veli palatini
Supplied by third division of CNV
151
What muscles are in Arch 2
muscles of facial expression
some suprahyoids
stapedius
All supplied by CNVII
152
What muscles are in Arch 3
one trivial muscle (stylopharyngeus)
Supplied by CNIX
153
What muscles are in Arch 4
pharyngeal constrictors
muscles of soft palate and larynx
All supplied by CNX
154
Innervation of the tongue by which arches...
Anterior 2/3= 1st and 2nd arches
Posterior 1/3= 2nd, 3rd and 4th
(2nd is overgrown)
Epiglottis= 4th
155
Examples of what arch malformations can result in
(majortiy affect 1st arch)
- clearest impact on skeletal structures
- hypotrophic mandible
- Conductive hearing loss (incus and malleus)
- Part of syndrome??
156
What happens from 4th week of development
Formation of nasal cavity and primary palate.
- Invagination of the nasal placodes forms the nasal pits (primitive nasal cavity)
Primary plate begins the separation of the nasal and oral cavities anteriorly...
157
What happens from 6th week of developement
Maxillary processes extend from posterior aspect of mandibular arch.
- Forms the lateral borders of the mouth
2 processes grow mesially from the maxillary arches (tectospetal and palatine processes)
158
What happens from the 8th week of development
Palatal elevation
Embryo develop a cervical flexure- lifting the head away from cardiac bulge.
Tongue drops into FOM as mandible widens.
Palatal processes have no restraint and elevate into a horizontal position.
159
Intrinsic factors of palatal elevation
- Water
- Turgor
- Agents that dirsupt GAG synthesis tend to inhibit palate elevation
160
Week 10- Fusion of palatine processes
Completes at week 12
Processes contact and fuse.
| Fusion requires breakdown of the ectodermal covering of the processes to allow underlying ectomesenchyme to fuse.
161
Post-week 12...
Anterior 2/3 is invaded by bone.
Posterior 1/3rd invaded by muscle from 4th pharyngeal arch to form muscles of soft palate.
162
How is nose formed?
Frontonasal processes are compressed between max. processes to form a protruding nose
163
How is mouth formed?
Fusion of max. and mand. processes
164
What is macrostomia?
Failure of fusion of mand. and max. processes
165
What if cleft palateis?
800-1000 in uk/annum
Rare familial cleft carried on Chromosome
166
Contributory environmental factors to c.palate
During pregnancy:
- Heavy smoking
- heavy alcohol consump
- Folic acid deficiency
167
What is cyclops feti?
Failure of nasal placodes to develop so no nasal cavities
- eyes fused at midline
- excess tissue is pushed out as proboscis
