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BONE AND JOINT DISEASES
Osteoblasts: lay down new boneOsteoclasts: resorb (dissolve)
boneOsteocytes: help maintain bone Types of bone
(structural)Cortical/compact bone (80%)
!"Outer area of bone!"Compact à strength!"Has unique concentric
arrangement of Haversian system
Trabecular bone (20%)!"Inner area of bone!"Spongy!"Filled with
red or yellow marrow!"Lamellae are arranged in irregular
latticework =
trabeculaeHaversian system (osteon) in corticalboneOsteon
contains:
!"Haversian canal (contains blood vessels andnerves)
!"Concentric lamellae (concentric arrangement ofcollagen fibres
surround Haversian canal)
!"Osteocytes, lacunae (cavity in bone matrix containing
osteocyte) and canaliculi (channels that linklacunae)
Volkmann’s canals:!"Connect Haversian canals to periosteum
(outer lining of bone)
Interstitial lamellae:!"Lamellae in between Haversian systems
(not part of Haversian system)
Circumferential lamellae:!"Parallel to the surface (not part of
Haversian system)
Trabecular/spongy bone !"Has a higher surface area to mass
ratio!"Softer, weaker, more flexible!"Highly vascular!"Red bone
marrow!"Trabeculae aligned towards the mechanical
load distributionWoven bone
!"Immature bone!"Random organisation of collagen
fibres!"Mechanically weak!"More osteocytes per unit of
volume!"Higher rate of turnover
Found in:!"All foetal bone initially when the bone is laid
down!"Initial stage of fractures!"Paget’s disease (abnormal
enlargement and weakening of bone)
Bone cellsOsteoblasts
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(Fusion of macrophages)
Bone cellsOsteoblasts
!"Bone forming cell!"Produce organic bone matrix (osteoid) which
then becomes mineralized (calcium, phosphate)!"Regulate
differentiation and activity of osteoclasts!"Arises from stem cell
= osteogenic cell
Osteocytes!"90% of the bone!"Terminally differentiated
osteoblast!"Initiate mineralisation!"Trapped within mineral
deposit!"Located in lacunae!"Regulate and communicate with other
cells
and vessels via canaliculi!"Exchange nutrients and waste via
canaliculi!"Mediate bone repair!"Mechanosensor
Osteoclast!"Large, multinucleated (fusion of
monocytes/macrophages)!"Attach to bone surface (ruffled
border)!"Resorb bone by release of lysosomal
enzymes (break down organic matrix)and acid (H+) release (breaks
downinorganic matrix)
!"Resorption bay = H owship’s lacunaeBone remodelling
!"Ongoing replacement of old bone by new bone tissue!"Respond to
mechanical loading!"Repair and prevent micro damage (wear and
tear)!"Release growth factors and minerals (calcium and phosphate)
stored in matrix into circulation!"Ongoing process!"Osteoclasts
resorb bone, osteoblast reforms bone
Osteoclast regulation by RANK/RANKL and OPG!"Preosteoclasts
express receptor molecules on surface called ‘RANK’!"Ligand (RANKL)
binds to RANK, activating osteoclast!"2 forms of RANK ligand =
attached to osteoblast or free!"RANKL (ligand) able to bind to RANK
and OPG (decoy receptor)!"Binding to OPG inhibits binding to RANK =
inhibits osteoclast activation!"OPG binding prevents excessive bone
resorption
Factors affecting bone metabolismLocal (autocrine)
!"RANKL binding to RANK receptor à activates
osteoclasts!"Osteoprotegerin (OPG) à inhibits
osteoclasts!"Sclerostin à inhibit osteoblasts!"Inflammatory
cytokines à activate osteoclasts
Systemic!"Hormones
• Parathyroid hormone (PTH) induces osteoclast activity and
recruitment à stimulates boneresorption (increases blood
calcium)
• Calcitonin à inhibits bone resorption (decreases blood
calcium)• Oestrogen à regulates RANKL expression
!"Vitamins and minerals• Vitamin D and C
Bone pathologiesOSTEOPOROSIS
!"Balance of bone formation and bone resorption disrupted!"The
loss of bone mass leaves the trabecular bone thinner and
porous!"Bones prone to fracture
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OSTEOPOROSIS!"Balance of bone formation and bone resorption
disrupted!"The loss of bone mass leaves the trabecular bone thinner
and porous!"Bones prone to fracture!"Bone mineral density is
reduced 35% - 65%!"80% of those affected are women
Primary osteoporosis!"Postmenopausal!"Senile!"Idiopathic (no
known cause)
Secondary osteoporosis!"Endocrine disorders!"Rheumatoid
arthritis!"Vitamin D
deficiency!"Neoplasia!"Immobilization!"Gastrointestinal
disorders
Risk factors!"Genetic factors!"Low peak bone mass!"Abnormal bone
structure!"Female!"Older age!"Alcohol!"Calcium and vitamin D
deficiency!"Hormonal – lack of oestrogen!"Reduced physical
activity
Osteoporosis prevention and treatment!"Diet!"Hormone replacement
therapy (HRT)!"Bisphosphonates (drug that stops bone
resorption)!"Calcium!"Vitamin-D!"Denosumab (RANK inhibitor - stops
bone resorption)
OSTEOARTHRITIS!"Most common joint disease!"Progressive erosion
of articular cartilage!"Caused by biochemical and metabolic
alterations!"Changes in underlying subchondral bone!"Minimal
inflammation secondary to cartilage erosion!"Matrix
metalloproteinases (MMPs) are primary enzymes responsible for
degradation of cartilage!"Common sites: hip, knee, shoulder, spine,
foot
Primary osteoarthritis: absence of any known underlying diseases
(wear and tear damage)Secondary osteoarthritis: due to some
underlying disease (diabetes, obesity, trauma)Risk factors:
!"Age!"Obesity!"Joint injury!"Long-term overuse!"Malformed
joints
Management of osteoarthritis!"No treatments available to prevent
development and progression!"Managing symptoms such as pain,
stiffness and swelling!"Maintaining healthy weight!"Improving joint
mobility and flexibility, surgery
RHEUMATOID ARTHRITIS!"Chronic inflammatory!"Autoimmune
disease!"Approx. 1% of global population!"Female >
male!"Destruction of the joint!"Extra-articular manifestations:
skin, blood vessels, heart, lung, muscles!"Unknown
cause!"Rehumatological = autoimmune!"Antibodies produced against
articular cartilage in joints à causes autoimmune response
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!"Unknown cause!"Rehumatological = autoimmune!"Antibodies
produced against articular cartilage in joints à causes autoimmune
response
Pathologies of rheumatoid arthritis joints!"Hyperplasia à
thickening!"Accumulation of inflammatory cells!"Increased
vascularity!"Cartilage and bone erosion
Current RA treatments!"Anti-inflammatory
medications!"Immunosuppressive therapy!"Disease modifying anti
rheumatic drugs (DMARDs)!"Surgical treatments (arthroplasty – joint
replacement, synovectomy – removal of cartilage)
CHRONIC PERIDONTITIS!"Chronic inflammatory disease of
periodontium (tooth supporting structures)!"Results in erosion of
alveolar bone à loss of teeth!"Affects over 65% of adults above
65
Common characteristics!"Onset: any age, most common in
adults!"Plaque initiates condition!"Subgingival calculus
(calcification of bacterial plaque) common finding!"Slow
progression!"Modified by local factors/systemic
factors/stress/smoking
Risk factors!"Prior history!"Local factors:
• Plaque• Microbiological factors• Trauma
!"Systemic factors:• Smoking• Diabetes• Nutritional factors•
Osteoporosis
!"Environmental and behavioural factorsTreatmentsNon-surgical
procedures
!"Scaling!"Root planning!"Antimicrobial therapy!"Improvement in
oral hygiene
Surgical procedures!"Pocket reduction surgery!"Correction of
morphological/anatomical defects
FORENSIC PATHOLOGY What is forensic pathology?Pathology: Study
of injury and diseaseForensic pathology: how this applies to the
law
!"Autopsies ordered by the state coroner• 50% natural disease•
20% suicides• 15% motor vehicle accidents• 5% homocides
Disaster victim identification!"Formal process of identifying
victims in cases of multiple deaths (pathologists examine bodies
in
mortuaries)!"Antemortem data: before death!"Postmortem data:
after death – pathology, DNA, fingerprints, dental
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!"Formal process of identifying victims in cases of multiple
deaths (pathologists examine bodies inmortuaries)
!"Antemortem data: before death!"Postmortem data: after death –
pathology, DNA, fingerprints, dental
Problems!"Heat (affects body
preservation)!"Dehydration!"Smell!"Flies
What is death?Full cessation of the functions in a biological
organismSomatic death: death of the bodyBrain death: cessation of
brain activityCell death: death of individual cells and
tissuesForensic problems
!"When does death occur?!"Can cellular metabolism continue after
somatic death? (yes)!"How does this affect dating of wounds,
injuries and disease?
Steps in assessment!"Scene
examination!"Autopsy!"Report/synthesis!"Court (if required)
The reason for a pathologist at the scene!"Nature of death
(homicide, natural?)!"Time of death!"Discussion of other issues
(unusual markings etc.)
Time of death!"Temperature: body temp falls after
death!"Lividity (pooling of blood)!"Rigor mortis (stiffening of
muscles
Temperature!"Undisturbed scene with core and environmental
temperature!"Charts!"“rule of thumb”!"Great variation
Lividity!"Post-mortem settling of blood (e.g. lying on back =
blood pools at back, settles after 8hrs)!"Can be used to tell if
body has been moved!"Commences after 0.5 hrs, fixes at 8 hrs
Rigor mortis!"Stiffening of muscles – commences at 1-2 hours,
passes off at 24-48 hrs!"Jaw, arms legs
Putrefaction!"Part of decomposition process!"Green stained
skin!"Skin slippage!"Blisters!"Purging (reddish fluid comes out of
mouth and nose)
Identification of bodies!"Visual: notoriously
inaccurate!"Dental: very accurate!"Finger prints: very
accurate!"DNA: very accurate!"Circumstantial: inaccurate
Marine predator attacks!"Injuries not well categorized!"Bodies
not recovered!"Incomplete or decomposed!"Wounds not well
preserved
Types of cases!"Those with bites to limbs who exsanguinate
(loose blood)!"Those not recovered or fragmented!"Differences in
species/type of attack
Characteristics of bite marks!"Major wounds in cases often
consist of circular incisions 20-25cm across
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!"Those not recovered or fragmented!"Differences in species/type
of attack
Characteristics of bite marks!"Major wounds in cases often
consist of circular incisions 20-25cm across!"Sharply defined
margins with minor scalloping, highly characteristic of damage
produced by
separated edges of teeth of great white shark