Download Limb development - Sydney University Medical Society

Block 2 –
Musculoskeletal
Learning Objectives
Arunan Sriravindrarajah
The following lecture objectives were ordered thematically
TABLE OF CONTENTS
Limb development .................................................................................................................................................. 3
Development of Limbs ............................................................................................................................... 3
Body Parts ............................................................................................................................................................... 4
Upper Limb – Clinical Anatomy .............................................................................................................. 4
Lower limb – Vessels .................................................................................................................................. 7
Lower limb – Nerves ................................................................................................................................... 7
Lower Limb – Clinical Anatomy .............................................................................................................. 8
Vertebral Column – Introduction ........................................................................................................... 8
Vertebral Column – The Neck ................................................................................................................. 9
Vertebral Column – The Low Back ........................................................................................................ 9
Vertebral Column – Radiology .............................................................................................................. 10
Causes and Prevention of Back Pain................................................................................................... 10
Principles of Management of Back Pain ............................................................................................. 12
Bone ...................................................................................................................................................................... 12
Bone and Tooth Structure and Function ........................................................................................... 12
Mineral Homeostasis ................................................................................................................................. 14
Osteoporosis: Hormonal Issues ............................................................................................................ 14
Clinical Management of Osteoporosis ................................................................................................ 15
Falls in the Elderly ..................................................................................................................................... 16
Principles of Rehabilitation ..................................................................................................................... 17
Infections of Bones and Joints .............................................................................................................. 17
Joints ..................................................................................................................................................................... 18
Pathogenesis and Clinical Spectrum of Osteoarthritis ................................................................. 18
Management of Osteoarthritis .............................................................................................................. 19
Overview of Drugs in Arthritis – NSAIDs & DMARDs ................................................................... 20
Overview of Medications in Arthritis – Steroids ............................................................................. 21
Autoimmune Diseases .............................................................................................................................. 22
Pathology and Pathogenesis of Rheumatoid Arthritis .................................................................. 23
Uric Acid Metabolism and Medications ............................................................................................... 25
Muscle .................................................................................................................................................................. 25
Physiology of Muscle ................................................................................................................................. 25
Exercise and Muscle .................................................................................................................................. 26
Nerve .................................................................................................................................................................... 27
Nerve Structure and Conduction .......................................................................................................... 27
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Synaptic Transmission and the Neuromuscular Junction ........................................................... 28
Clinical Anatomy of the PNS .................................................................................................................. 29
Skin ....................................................................................................................................................................... 29
Photobiology UV and the Skin ............................................................................................................... 29
Prevention of Skin Cancers .................................................................................................................... 30
Other..................................................................................................................................................................... 32
Radiation Safety ......................................................................................................................................... 32
Impact of Chronic Illness ........................................................................................................................ 32
System .................................................................................................................................................................. 32
Shock – An Overview ............................................................................................................................... 33
Biochemical Syntheses ............................................................................................................................ 33
Basic Biochemical Tests – Indications and Interpretation .......................................................... 35
Introduction to Nuclear Medicine and Musculoskeletal Nuclear Medicine ............................ 36
General and Local Anaesthetics............................................................................................................ 37
Action of Opioids on Cells and Systems ............................................................................................ 37
Clinical Pharmacology of the Opiates ................................................................................................. 39
Health Law ............................................................................................................................................................ 40
Health Law 3 – Consent, Knowledge and Power ............................................................................ 40
Health Law 4 – Substitute Decision Makers ..................................................................................... 40
PPD ....................................................................................................................................................................... 41
Teamwork ..................................................................................................................................................... 41
Peer Assessment ........................................................................................................................................ 42
PPD – Giving and Receiving Feedback ............................................................................................... 42
Seminars ............................................................................................................................................................... 43
Upper and Lower Limb Radiology ........................................................................................................ 43
Blood Pressure and Its Fluctuation ..................................................................................................... 44
Impact – Musculoskeletal Disease in the Community ................................................................. 46
Team Approach to Musculoskeletal Disease .................................................................................... 46
Clinicopathology of Common Skin Tumours .................................................................................... 47
Clinicopathology of Diseases Causing Bone or Joint Pain ........................................................... 49
Introduction to EBM .................................................................................................................................. 50
How to Use Auto Antibodies for Diagnosis ....................................................................................... 50
Study Types ................................................................................................................................................. 52
Imaging the Musculoskeletal System ................................................................................................. 53
2
LIMB DEVELOPMENT
DEVELOPMENT OF LIMBS

Explain the tissue interactions that determine the three dimensional
development of the limbs
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There are two specialised structures in the limb bud:
o Apical Ectodermal Ridge – ridge of cells which goes around the dorsoventral axis of the limb
o Zone of Polarising Activity – group of cells of the posterior margin of limb bud
o Both these structures have signalling molecules specific to themselves, which signal to the
cells within the limb to allow limb structures to form in a very controlled way
 This ensures the orientation and direction of limb development is normal (i.e.
proximal structures and distal structures are the right way)
 Every cell in the limb bud is experiencing a different chemical gradient based on the
different molecular signals to enable controlled outgrowth of the limb
 This is highly complex, which means there are several possible ways for
something to go wrong with the growth / orientation of the limb
Limb growth in the proximo-distal axis is determined by the apical ectodermal ridge (AER)
o Fgf8 produced by cells in the AER keeps the mesenchyme of the limb bud proliferating, stops
differentiation, allows the limb to grow out and specifies the structures of the limb
Zone of Polarising Activity (ZPA) causes a posterior to anterior gradient to go across the limb and this
specifies finger vs. thumb
o Shh gene (sonic hedgehog) is expressed at the ZPA, which sets up a gradient (posterior to
anterior) across the limb bud that determines the differentiation of the fingers
Dorsal and Ventral Ectoderm determines the dorsal-ventral axis through the release of Genes:
o Wnt7a, which is expressed dorsally
o En-1, r-fng and Lmx1, which is expressed ventrally
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
List the stages of foetal development
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Blastocyst: first 2 weeks
Embryonic: week 3 to week 8
Foetal: week 9 onwards

Describe the time lines for development of limb buds
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End of Week 4 – Limb buds first appear
Week 5 – Hands appear (two fore limb buds) prior to feet (two hind limb buds) by a couple of days
Week 6 – Digital Rays of the hand (i.e. webbed fingers)
Week 7 – Digital Rays of the feet (i.e. webbed toes)
Week 8 – Webbing surrounding the fingers should disappear

List the genes involved in limb development
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The genes Tbx4, Tbx5 and Pitx1 influence the identity of the limb
o Tbx4 – hindlimb
o Tbx5 – forelimb
o Tbx2 & Tbx3 – both limbs
o Pitx1 – hindlimb
Limb position is determined by Hox genes in embryonic trunk

Outline the role of programmed cell death in limb development
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The limb grows out as an elongated structure, and then cell death is programmed to occur, to allow
the bones to form and to shape the hand, etc.
o Programmed Cell Death is necessary for the shaping of the limb structures
3

Describe the pathogenesis of common limb malformations
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Syndactyly = Fusion of digits, BMP or Shh disruption
Polydactyly = Extra digits, Shh disruption
Amelia = Absence of an entire limb (e.g. early loss of Fgf signalling)
Adactyly = Absence of digits (e.g. even later loss of Fgf)
Thalidomide resulted in loss of immature blood vessels which ultimately resulted in longer exposure
to FGF8 in AER, which results in more distal structure development rather than growth of the
proximal structures
BODY PARTS
UPPER LIMB – CLINICAL ANATOMY

Explain the nerve supply of the upper limb and the syndromes due to their
dysfunction
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Nerve supply of upper limb is mainly via the Brachial Plexus; the key nerves include:
o Axillary Nerve;
o Radial Nerve;
o Ulnar Nerve;
o Musculocutaneous Nerve; and
o Median Nerve
When examining patient for nerve lesions of the upper limb, there is a need to examine:
o Brachial Plexus
 Distraction of C5 and C6 will result in Erb-Duchenne Paralysis  this is evidenced
clinically by the arm being pronated
 Distraction of T1 results in paralysis of all intrinsic muscles of the hand and area of
anaesthesia along the T1 dermatome
 This can result in ‘Klumpke’s Paralysis’ which causes a ‘claw hand’
o Median Nerve
 Test - Touching the thumb to little finger indicates the median nerve is OK
 Damage - Damage to median nerve will prevent opposition of thumb
o Ulnar Nerve
 Test – Abduction of fingers indicates the Ulnar Nerve is OK
 Damage – Damage to Ulnar Nerve can cause paralysis and a ‘claw hand’ for the
lateral one and a half digits
o Radial Nerve
 Test - Dorsiflexion of wrist indicates Radial Nerve is OK
 Damage – Damage to Radial Nerve will result in wrist drop
The three important nerves associated with the humerus are the Axillary Nerve, Radial Nerve and
Ulnar Nerve
o Fractures in the upper humerus or dislocations in the shoulder can damage the axillary nerve
 Before relocating a dislocated shoulder, always test function / lesions of the axillary
nerve  do this by looking for area of anaesthesia on the lateral side of the deltoid
muscle
o Fractures in the shaft of the humerus can affect the radial nerve
o Fractures in the lower humerus can damage the ulnar nerve (note: pins and needles from the
‘funny bone’ are caused by contact with the ulnar nerve)
o Fractures in the supracondylar area of the humerus can be highly problematic as it can affect
the radial nerve and ulnar nerve (as these nerves are closely applied to the bone at this area)
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
Explain the role of anatomical structures in the clinical manifestations of
Carpal Tunnel Syndrome
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Carpal Tunnel Syndrome is due to compression of the Median Nerve in the Carpal Tunnel
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No vessels go through the Carpal Tunnel (only tendons and the Median Nerve go through the
Carpal Tunnel)
Relieving of Carpal Tunnel Syndrome involves division of the Carpal Ligament (i.e. Flexor
Retinaculum)
 This increases space available for structures to go through in the Carpal Tunnel and
hence will relieve compression of Median Nerve
 Note it is important to place something under the Carpal Ligament to protect the
Median Nerve
 When operating on the carpal tunnel, it is critical to not affect the nerve innervating
the thenar muscle (recurrent branch of median nerve) as this enables opposition of
the thumb (which is critical!!!)
 It is also important to fix the wrist in a slightly extended position
immediately following the operation to prevent bowstringing of the flexor
tendons  movement can then be gradually increased over time in a way
that will prevent future bowstringing

Describe the anatomical structures causing the Supraspinatous syndrome
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Supraspinatous locks the head of the humerus in the glenoid cavity
o This enables other muscles (e.g. deltoid) to operate on the humerus without pulling it out
from the socket
o Supraspinatous syndrome or a rupture of the supraspinatous will prevent initiation of
abduction of the shoulder (note: after a certain point of abduction, the deltoid muscle will be
responsible for further abduction)
MRI’s are very useful for identifying rotator cuff syndromes and supraspinatous syndromes

Describe the bones and joints in the upper limb
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Clavicle - The most common long bone in body that is fractured in Clavicle (i.e. Collarbone)
o Clavicle will usually fracture in the middle third
o This is due the opposing forces of gravity (downward) on the lateral end of the clavicle and
the sternocleidomastoid muscle (upward) on the medial end of the clavicle
o Rupture of the coracoclavicular ligaments (conoid and trapezoid parts) are very serious
injuries (worse than fracture of clavicle)
 Treatment requires screwing the ligament back into place and will take ~6-8 weeks
for recovery
 In contrast, a clavicle fracture takes only ~2-3 weeks to recover from
Shoulder Joint - The most common dislocation in the body is the shoulder joint
o Shoulder joint is a very shallow ball and socket, and hence dislocation is very common
o Classical shoulder dislocation involves the head of the humerus coming out of the glenoid
fossa of the scapula and moving into a bursa that is deep to the subscapularis
o Clinical identification of shoulder dislocation in a sharp angle of the shoulder joint (i.e.
smoothness of deltoid muscle is completely lost)
Humerus - Fractures in the supracondylar area of the humerus can be highly problematic as it can
affect the radial nerve and ulnar nerve (as these nerves are closely applied to the bone at this area)
o Supracondylar fracture must ALWAYS be repaired by internal fixation by fixing the distal end
of the humerus to the shaft of the humerus through plates and screws
o Supracondylar fractures of children can cause damage and /or kink the brachial artery
 Internal fixation though is not used to repair the fracture as this will close the
epiphyses and prevent any more growth of the bone
 Instead, the arm is placed in a sling as a means of repair
o Occlusion of the brachial artery by the fracture can result in Volkman’s Ischaemic
Contracture
 This causes ischaemia of the muscles resulting in a ‘claw hand’ (though there is no
sensory loss of the hand)
Radius – Head of the radius is provided blood supply through shaft of radius, so any fractures of neck
of radius will disrupt blood supply for head of radius
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Dislocation of the elbow joint will result in medial epicondyle becoming significantly apart (in
contrast to supracondylar fracture where they will still remain normally orientated)
Fractures in the proximal third of radius will result in biceps supinating the proximal third of
the radius, whilst the pronator teres will pronate the distal two-thirds of the radius
 Treatment will require supinating the distal two thirds and fixing the fracture with
the radius in full supination
Fractures in the distal third of the radius though will result in the biceps and pronator teres
offsetting each other in its action on the proximal two thirds of the radius
 Therefore, treatment will involved fixing the radius in the neutral position (rather
than supinated or pronated position)
Colles Fracture of the Distal Radius is common in the elderly who fall on their outstretched
hand
 This will result in a ‘dinner fork’ appearance of the hand, whereby the wrist is
dorsally elevated due to the change in position of the distal part of the radius
 Treatment involves flexion of the wrist and ulnar deviation (i.e. hand angled laterally
towards the ulnar), as this will fix the distal radius fracture in the right position and
then placing into a cast

List the anatomical structures involved in the Thoracic Outlet Syndrome
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Thoracic Outlet / Inlet Syndromes are associated with an additional cervical rib that lifts up all the
above neurovascular structures going to the upper limb so they are kinked and compressed
o The neurovascular bundle (e.g. subclavian vein, artery and brachial plexus) going to the
upper limb will be affected
 Obstruction of the vein can cause swelling of the arm and venous congestion of the
arm
 Obstruction of the subclavian artery due to Thoracic Outlet / Inlet syndromes can
result in microemboli to form
 These microemboli will shift down to the extremities (e.g. fingertips) of the
upper limb (and this can also happen in the lower limb)
 These microemboli cause gangrenous areas in the extremities  several
gangrenous areas is called “Trashing” of the Upper (or Lower) Limb
 If the nerve is kinked, it’s usually the T1 nerve and cause paralysis of the intrinsic
muscles in the hand and an area anaesthesia in the T1 dermatome in the arm
o Note: Scalenus anterior separates the subclavian vein and subclavian artery as they go over
the first rib
o Note: The brachial plexus lies posterior to the subclavian artery

List the bones in the hand
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Scaphoid and Lunate are the key carpal bones for clinical conditions when examining the carpal area
o The carpal ligament (i.e. Flexor Retinaculum) is attached to the Pisiform, hook of the Hamate,
the crest of the Trapezium and the crest of the Scaphoid
Fractures of the scaphoid that are at the ends of the bones can cause avascular necrosis of the end
part of the scaphoid as the nutrient foramina are in the middle of the scaphoid
o Tenderness of the anatomical snuff box may indicate a scaphoid fracture, as the scaphoid
bone (and radial artery) are deep in the anatomical snuff box
o Treatment of scaphoid fracture will require immobilising first metacarpal as this articulates
with the scaphoid
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Infections - Infections in the flexor compartment of the hand are problematic due to the presence of
the synovial sheaths around the flexor tendons
o Infections (especially bacterial) will cause the loss of the smooth, gliding properties of the
tendon within the synovial sheath resulting in stiff fingers
Infections – ‘Whitlow’ is an infection of the Distal Pulp Space of the Phalanx
o Can be caused by pricking finger with a rose thorn
6
o
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This results in swelling of the distal pulp space which results in large pressure build-up and
hence significant pain in the distal pulp space
o The pressure can cause occlusion of the arteries in the finger resulting in avascular necrosis
of the distal phalanx and infection of the bone of the distal phalanx (osteomyelitis)
Anaesthetic – Insertion of Anaesthetic into the arteries supplying the hand will cause significant
damage to the tissue
o Hence, Anaesthetesist always prefer providing anaesthetic to the back of the hand as there
are no arteries in this area
Dominant Arteries – Some people have a dominant radial artery, some people have a dominant ulnar
artery whilst others have equally dominant radial and ulnar arteries
o Never place a needle into a dominant artery as this will significant restrict blood supply
o Identify the dominant artery using the Allen’s Test
 Allen’s Test involves squeezing the hand into a fist and then occluding both radial
and ulnar arteries
 The wrist will be white with both arteries occluded
 Release the radial artery and it will flush with colour, and then release the
ulnar artery and it will flush with colour
 If there is a delay in flushing, then the alternate artery is the dominant
artery into which you should never place a needle
LOWER LIMB – VESSELS

Identify the major arteries of the lower limb.
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
Identify the major relationships of the arteries of the lower limb.
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
Identify the deep and superficial components of the venous system of the
lower limb, including the deep venous plexus of the posterior leg region.
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
Identify some of the arteries and veins of the lower limb in contrast
radiographs.
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LOWER LIMB – NERVES

Identify the lumbar and sacral plexuses and note their key relationships.
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
Identify the femoral, obturator, superior and inferior gluteal, common
peroneal and tibial nerves, and some of their branches, and trace their
courses and note their key relationships.
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
Revise the boundaries, contents and their relationships, of the major
topographical regions of the lower limb.
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7

Discuss a selection of matters relating to the structure of the lower limb.
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LOWER LIMB – CLINICAL ANATOMY

Describe the structural changes in dislocation and fracture of the hip joint
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
Describe the structures of the knee joint and consequences of fractures
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
Describe the components of the ankle joint and consequences of fractures
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
Describe the bones within the foot and consequences of factures
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
Describe the anatomy of the sciatic nerve and the structures it supplies
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
List the structures passing under the inguinal ligament
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
List the structures in the popliteal fossa
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
Describe the arteries and veins of the lower limb and the consequences of
ischaemia
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
Describe the lymphatic drainage of the lower limb
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VERTEBRAL COLUMN – INTRODUCTION

Describe regions and curvatures of the vertebral column and the number of
vertebrae in each region
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
Explain the basic components of a typical vertebrae and their function
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
List the differences between cervical, thoracic and lumbar vertebrae
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
Describe and classify the joints associated with the vertebral column
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Describe the location and general function of ligaments
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Describe the true back muscles, their relative positions and actions
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
Explain the relationships of neural structures and meninges to the vertebral
column, including the points of exit of spinal nerves
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VERTEBRAL COLUMN – THE NECK

Describe cervical vertebrae and their parts on isolated bones, articulated
skeletons and radiographs
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Describe the joints of the cervical spine and the movements at these joints
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
Describe the boundaries and contents of the cervical vertebral canal and the
effect of impingement on the cervical spinal cord
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
Describe the exit points of cervical spinal nerves and common causes of
encroachment on the intervertebral foramen
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
Describe where nerve roots/spinal nerves emerge from cervical spine eg
C5/6 IVF
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
Describe and demonstrate dermatome and myotome tests for the upper limb
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
Describe the course of the vertebral artery and the parts of the nervous
system it supplies
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VERTEBRAL COLUMN – THE LOW BACK

Describe the general anatomical organisation of the vertebral column - from
cervical vertebra to coccyx
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9

Describe the anatomical organisation of the upper (cervical) vertebral
column
o the neck;
o the bones;
o joints;
o muscles (movements); and
o nerves
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
Describe the anatomical organisation of the lower vertebral column;
o the bones;
o joints;
o muscles; and
o nerves
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VERTEBRAL COLUMN – RADIOLOGY

Outline the principles of radiography, x-ray CT, MRI and bone scintigraphy
(including contrast media) in the context of the spine
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
List the imaging tests available and their role in testing specific clinical
hypotheses
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
Describe the differences between imaging the neural and musculoskeletal
structures of the vertebral column.
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
Explain the choice of appropriate imaging to order and when not to order
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CAUSES AND PREVENTION OF BACK PAIN

List the causes of back pain and associated red flags
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Vast majority (~97%) of low back pain will be due to Mechanical problems rather than NonMechanical or Visceral Diseases
o However, it is often difficult to specify the exact cause of the Mechanical Back Pain and
instead the pain is characterised as non-specific
Main causes of back pain are:
o Non-Specific (85%-98%)
o Sciatica
o Canal Stenosis
o Fracture
o Serious Disease
o Visceral
Key Red Flag Diagnoses include:
o Spinal Stenosis / Radiculopathy
o Cancer
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Cauda Equina Syndrome
Vertebral Compression Fracture
Vertebral Infection

Describe the pathology of back pain
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There are a range of pain-sensitive structures in the back including:
o Facet Joints
o Intervertebral Disc (outer fibres of Annulus)
o Vertebrae
o Ligaments
o Muscles
o Nerves
Pathoanatomical source of Low Back Pain is unclear
Better understanding exists of epidemiological causes

List the clinical features and risk factors for new back pain
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Key Red Flags for Detection of Fracture include:
o Prolonged Corticosteroid Use
o Contusion / Abrasion
o >70 year old Female with corticosteroid usage
Key Red Flag for Detection of Cancer is a prior history of cancer
Risk factors include:
o Long-Term
 Smoking
 Low Physical Fitness
 Low Social Class / Education
 Body Build
 Age
o Transient
 Lifting Awkwardly
 Distraction
 Fatigue
 Slip/trip/fall
 Alcohol
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
List the appropriate clinical investigations for back pain
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Whilst there are several different structures in the back that could cause pain, there are no simple
clinical tests that can identify the particular cause of the pain
o Laboratory tests are available to assess specific structures, but this is inconvenient, timeconsuming and costly to perform and hence are often not performed
o Hence, it is difficult to be able to identify the specific disease process and so most treatments
offered are generalised
o Whilst there are diagnostic tests that increase the level of certainty a small amount, none of
these diagnostic tests are definitive (i.e. neither specific or sensitive)

Outline the natural history of back pain and the risk factors for chronicity
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~50% of patients will recover within 2 weeks (provide simple painkillers in these circumstances and
ask patient to return in 2 weeks)
Wait for ~1-2 weeks following first line care before referring patient to second line care (i.e. stronger
medicines, physical therapies)
Risk factors include:
o Individual Risk Factors (per above)
o Physical Risk Factors (per above)
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Psychosocial Risk Factors (job satisfaction, work ‘stress’, low social support, etc.)
Genetic Risk Factors

Outline procedures for preventing low back pain
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Treatment / Prevention of Back Pain requires a multifactorial approach given the complexity and
uncertainty of the causes of back pain
o Avoid risk factors (e.g. no smoking, physically active, healthy weight, use back wisely, enjoy
life and work)
o Exercise has been shown to effective at preventing low back pain
o ‘Active back school’ (both exercise and education) was also shown to lead to better
outcomes
PRINCIPLES OF MANAGEMENT OF BACK PAIN

Describe the role of active and passive physiotherapy in the management of
back pain
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Key treatment for back pain is to remain active; physiotherapy will assist with ensuring patient
exercises (and potentially can also help them reduce weight too, which will assist in minimising back
pain)

Describe the role of local anaesthetic blocks in the management of back pain
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Pain relief will help patient remain as active as possible, which is critical for recovery from back pain

Describe the specific treatment for anatomically confirmed disorders
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Difficulty with imaging is that many disorders may be asymptomatic
Imaging should be avoided as it will identify these asymptomatic issues and may result in unnecessary
treatment (that does not resolve back pain)

Outline the natural history of most clinical presentations of back pain
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~50% of patients will recover within 2 weeks (provide simple painkillers in these circumstances and
ask patient to return in 2 weeks)
Wait for ~1-2 weeks following first line care before referring patient to second line care (i.e. stronger
medicines, physical therapies)
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
Outline the functional improvement associated with rehabilitation
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Rehabilitation / physical activity will provide the most rapid and complete recovery, as well as less risk
of recurrent problems

List future developments in the treatment of chronic low back pain
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Treatment of Chronic Low Back Pain should be focused on providing pain relief and maximising
activity levels
Imaging should not be used as a default, but rather only if there is a high risk of fracture or cancer
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BONE
BONE AND TOOTH STRUCTURE AND FUNCTION

Explain the metabolic processes involved in bone turnover
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Osteocytes sense mechanical forces and will be involved in signalling to create additional bone (or
replace lost bone) to resist deformity if the mechanical forces are such that the bone would otherwise
be deformed
Whilst osteoclasts will dissolve mineral and breakdown bone, this releases the growth factors within
the bone which will act to attract new bone
RANK Ligand (RANKL) is expressed on the surface of Osteoblast (or Stromal Cells) and will bind to the
RANK receptor on the pre-osteoclast monocytes  this binding will induce the pre-osteoclast to
differentiate into an osteoclasts
o Note Osteoblasts also express the protein Osteoprotegerin (OPG) that binds to RANKL to
prevent it from binding to and activating the pre-osteoclasts
o Hence, the ratio of RANKL to OPG will be important in determining the equilibrium level of
bone formation and bone absorption

List the cells involved in bone metabolism
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Osteoblast (bone formation)
Osteoclast (bone resorption)

Describe the composition of bone matrix
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Collagen (gives bone tensile strength)
Non-collagenous proteins (e.g. proteoglycans, growth factors, etc.)
Bone Mineral (i.e. Calcium and Phosphate as Hydroxyapatite)

Describe the structure of bone
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Bone consists of two different components: Trabecular and Cortical (i.e. compact) bone
o Cortical bone is hard bone of the outer edge of the overall bone that makes up most of the
bone shaft (as well as outer parts of spine in addition to scapula)
o Trabecular bone contains the bone marrow and as such may appear red (as bone marrow
possesses haemopoietic cells)
o These merge together at the endosteum
Osteoblasts will initially lay down bone matrix without minerals (mainly consisting of collagen) which
is referred to as “Osteoid”
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
List the types of bone and their distribution throughout the skeleton
-
Spine, wrist and hip have relatively higher proportions of trabecular bone (rather than cortical bone);
this is due to why spine, wrist and hip fractures are particularly common in low trauma fractures (i.e.
fall from standing height)

List the procedures for assessing bone status in patients
-
Bone Densitometry (e.g. DEXA scan)
Ultrasound
Biopsy
Quantity / Quality (e.g. rates of bone turnover, cell death, etc.)

List the cells and structural components of teeth
-
Ameloblasts = lay down enamel - before tooth erupts from gum
o Enamel is a very dense matrix of closely packed collagen and large closely packed
hydroxyapatite crystals; this is very resistant to acid attack
o Fluoride adds to the Enamel and assists the Enamel to withstand Acid
Odontoblasts = lay down dentine
o Collagen fibres in dentine extend to alveolar bone
Osteoblasts and osteoclasts in alveolar bone
-
13

Describe cavity formation in teeth
-
Bacteria form a plaque of teeth; they breakdown food / carbohydrates producing acid
Acid dissolves mineral of Enamel, whilst proteolytic enzymes break down matrix
Destruction of enamel results in cavities (i.e. caries)
MINERAL HOMEOSTASIS

Outline the concept of peak bone mass, bone density and fracture risk
-
Peak bone mass 20-30years (after which rate of resorption > rate of formation)
o This is determined by genetics, exercise, Ca2+ intake, adequate Vitamin D, sex steroids
The lower bone mass, the higher the fracture risk
Bone mass depends on peak bone density and rate of loss

Describe the role of hormones in the development and maintenance of bone
mass
-
Parathyroid Hormone (PTH) increases resorption of bone to increase Calcium levels, reduces Calcium
loss from kidneys and increases Phosphate loss from kidneys
o PTH production stimulated by low Calcium and inhibited by Calcitriol and high Calcium levels
Calcitriol increase absorption of Ca2+ and Phosphate ions from diet (though will also increase
resorption of bone by a small degree)
o This is formed from Vitamin D (production of which is stimulated by PTH, low Phosphate,
growth and pregnancy)
Calcitonin inhibits resorption of bone
o Calcitonin production stimulated by gastric hormones, High Calcium concentration and
Pentagastrin
FGF23 increase Phosphate wasting and decreases Calcitriol levels
o FGF23 production stimulated by Calcitriol, PTH and High Phosphate concentration
-
-
-

Explain the mechanisms of bone loss due to glucocorticoid excess or steroid
deficiency
-
Low sex steroids (e.g. Oestrogen, Testosterone) increase bone resorption and decrease bone
formation (as Oestrogen keeps Osteoblasts alive longer and inhibiting Osteoclasts)
Androgens also increase muscle size, which then necessitates an increase in the relevant bone size
Excess glucocorticoids inhibit Osteoblasts and inhibit sex hormones
-
OSTEOPOROSIS: HORMONAL ISSUES

Describe the concept and mechanism of osteoporosis
-
Osteoporosis = T-score<-2.5 (i.e. Bone mineral density more than 2.5 SD below the young normal
mean)
Loss of horizontal struts within Trabecular bone in Osteoporosis weakens bone; increases risk of
fracture
-

Outline the role of hormones in the development and maintenance of bone
mass
-
Lack of calcium intake will release hormones that increase bone resorption in order to release Calcium
Vitamin D required to absorb Calcium from diet and mineralise bone
Low sex steroids (e.g. Oestrogen, Testosterone) increase bone resorption and decrease bone
formation (as Oestrogen keeps Osteoblasts alive longer and inhibiting Osteoclasts)
14

Explain the interaction between mechanical loading, calcium-regulating
hormones and sex steroid hormones in maintenance of bone mass
-
Mechanical loading requires resistance to deformity  bone responds by adding more bone
Lack of calcium intake will release hormones that increase bone resorption in order to release Calcium
Sex steroids help to maintain normal balance between bone formation and resorption  low sex
steroids increase bone resorption and decrease bone formation

Outline the mechanisms of bone loss due to glucocorticoid excess or sex
steroid deficiency
-
Low sex steroids (e.g. Oestrogen, Testosterone) increase bone resorption and decrease bone
formation (as Oestrogen keeps Osteoblasts alive longer and inhibiting Osteoclasts)
Androgens also increase muscle size, which then necessitates an increase in the relevant bone size
Excess glucocorticoids inhibit Osteoblasts and inhibit sex hormones
-
CLINICAL MANAGEMENT OF OSTEOPOROSIS

Outline the components of modifiable and non-modifiable risk factors for
osteoporosis
-
Non-Modifiable
o Advanced Age
o Female Gender
o Previous Fractures
o Bad Genes (e.g. Maternal fracture, Skeletal geometry)
o Early Menopause
o Past co-morbidity
o Disability
Modifiable
o Life style and nutrition (e.g. low activity, low body weight, calcium and Vitamin D deficiency,
high salt intake, excess smoking / alcohol)
o Low bone mass
o High bone turnover
o High fall propensity (poor eye sight, sedatives...)
o Treatable (current) comorbidities (e.g. Hypogonadism, Hyperthyroidism, PHPT, Cushings)
o Bone-adverse medication (Glucocorticoids, Anticonvulsants, etc.)
-

Identify those clinical risk factors that have the greatest impact on future
fracture risk
-
An existing low-trauma fracture is the most important clinical risk factor for further osteoporotic
fractures
Advanced Age
Female

Explain the concept of relative versus absolute risk
-
Absolute Risk refers to total risk
Relative Risk refers to risk compared to a baseline (e.g. Relative Risk of Future Fractures vs. Person
with no Fractures)

Explain the association between bone mineral density and fracture risk
-
Bone mineral density is an important (though not the only) determinant of fracture risk
Each standard deviation decrease in bone densitometry will increase the fracture risk by 2x fold
15

Define the terms ‘osteopaenia’ and ‘osteoporosis’ (as per WHO criteria)
-
Osteopaenia = T-Score between -1.0 and -2.5
Osteoporosis = T-Score < -2.5

Outline components of clinical investigations into osteoporosis, and their
meaning
-
Imaging (including bone density scan)  can identify changes in density, existing / past fractures,
underlying disorders)
Blood tests (to exclude other causes)

Outline the major components of osteoporosis management
-
Pain management
Exercise programs
Increased Vitamin D / Calcium (if insufficient)
Bisphosphonates (inhibit bone resorption)

Identify major groups of pharmacological agents currently used to treat
osteoporosis (i.e. to prevent further fracture)
-
Bisphosphonates (inhibit bone resorption)
RANKL-Inhibitors (inhibit bone resorption)
Parathyroid Hormone (stimulate bone formation)
Calcium / Vitamin D
FALLS IN THE ELDERLY

Outline the epidemiology of falls in the elderly both in the community and in
institutions
-
~33% of people > 65 years have at least 1 fall per year
Higher in hostels and nursing homes

List the causes of falls in the elderly
-
Trip
Poor Balance (e.g. may be due to Gait issues, Postural Drop, Neurological Issues, etc.)
Slip
Dizzy (e.g. may be due to Vertigo, Syncope)
Weak Legs

List the consequences of falls in the elderly
-
~20-25% of presentations to ED of patients > 65 years
Head injuries
Soft-tissue injuries
Long-lie injuries (e.g. ulcers, dehydration, pneumonia)
Disability
Hospitalisation (including complications)
Institutionalisation

Describe the assessment and prevention of falls in the elderly
-
Screening Questions / Assessment (e.g. recurrent falls, difficulty in walking / balance, fear of falling,
etc.)
Prevention will use multi-factorial approach including:
-
16
o
o
o
Exercise
Adjustment of medications (especially Psychotropic)
Occupational Therapy
PRINCIPLES OF R EHABILITATION

Outline the concept of the International classification of Functioning,
Disability and Health (ICF, World Health Organisation)
-
This classifies health conditions according to the impacts (e.g. activities, participation, body function)
and its context (e.g. environmental, personal)
Definitions of rehabilitation are likely to be realigned to ICF

Describe the role of health care professionals in rehabilitation programs
-
A multi-professional approach is needed as several different professions will be needed in a
rehabilitation program

List the different settings in which rehabilitation is provided
-
Community
Nursing Care Facility
Hospital

Explain the application of rehabilitation principles and the ICF to a hip
fracture patient
-
Need to consider the different impacts of hip fracture and support available
Develop rehabilitation plan that accounts for these different factors

Outline the evidence for efficacy of rehabilitation for hip fracture
-
Coordinated multidisciplinary rehabilitation is beneficial due a reduction in ‘poor outcome’ (Number
needed to treat [NNT] ~ 25
INFECTIONS OF BONES AND JOINTS

Outline the spectrum of microbial pathogens (viruses, bacteria and fungi)
that can infect bone tissue and joints
-
Infection of bone usually caused by Pyogenic Bacteria or Mycobacteria (e.g. Staphylococcus Aureus,
Streptococci, etc.)

Explore sources of bone and joint infections in adults and children
-
Intravascular Source (e.g. IVDU, Dialysis, Endocarditis)
Immune Compromised
Commensal Flora around the body (e.g. Staphylococcus Aureus)
Open Fractures
Vascular insufficiency (e.g. diabetic patients); they lack the healing capacity needed resulting in bone
infections

Explain the role of laboratory testing and imaging in the diagnosis of bone
and joint infections
-
X-Ray is a helpful first-step; can identify bone irregularity, osteolysis, periosteal elevation
Nuclear Imaging (e.g. Technetium-99m bone scan) useful for identifying bone turnover
17
-
-
CT scans reveal bone changes earlier than X-Rays and will more easily identify bone changes; these
are more specific than bone scans too
MRI detects bone abnormalities and has the highest sensitivity and specificity in detecting
Osteomyelitis (changes in bone present earlier than other imaging techniques)
Bone biopsy (consider whenever possible)
Microbiology critical (to specifically identify the pathogen and hence determine best treatment)

Outline approaches to treatment and management
-
IV Antibiotics (~4-6 weeks)
Pain relief
Surgical excision or Amputation (only in severe cases)
Note: Antibiotics may be used prophylatically especially for open fractures
-
JOINTS
PATHOGENESIS AND CLINICAL SPECTRUM OF OSTEOARTHRITIS

Outline the definition of Osteoarthritis
-
-
Osteoarthritis is a disease of the ENTIRE joint organ and not due to individual tissue
o This will affect all the tissues of the joint organ and NOT ONLY cartilage
o From a doctor / radiologist perspective, this will involve several different changes such as
subchondral bone thickening, loss of cartilage, osteophytes, etc.
o Generally though, there is progressive loss of cartilage both in spread and depth of cartilage
in osteoarthritis
o Note: It is NOT due to “wear and tear” but rather an active disease process in response to
external signals
 While different joint tissues work together to maintain a healthy joint, they can also
work together to progress the disease process
Osteoarthritis is a disease of bone formation (rather than bone loss)
o There will increased bone thickening or new bone formation, but the bone has lower bone
mineral density resulting in increased turnover of the bone
Osteoarthritis for a patient is a ‘painful, dysfunctional joint’
Increased vascularity and nerves in osteoarthritis may be a key driver of the pain of osteoarthritis

List the clinical and radiological criteria that contribute to the diagnosis
-
Clinical Criteria / Signs
o Tenderness over the joint line
o Crepitus with movement of the joint
o Bony enlargement of the joint
o Reduced range of motion
o Joint swelling
o Joint deformity
o Instability/ laxity of the joint
o Heberden or Bouchard's Nodes (DIP and PIP joints respectively)
Radiological Criteria
o Osteophyte formation
o Joint space narrowing
o Subchondral sclerosis
o Subchondral cysts
o Intrarticular “loose” bodies
-
-

Outline the prevalence of Osteoarthritis
-
1/8 in Australians (~3 million people) are affected by Osteoarthritis
18
-
~63% of OA patients are female (i.e. female skew)
Whilst osteoarthritis typically affects older adults, over half of patients are working age and it is the
leading cause of premature retirement

Explain the aetiology of Osteoarthritis
-
Local Risk factors include:
o Obesity
o Injury
o Joint / Bone Alignment
o Certain occupations
Systemic Risk factors include:
o Female
o Elderly
o Genetics
o Nutrition
-

List the signs and symptoms of Osteoarthritis
-
Pain is mechanical in nature-that is occurs with activity, relieved with rest
Pain is usually insidious in onset
Morning stiffness is absent or lasts <30 minutes-usually described as gelling (short periods of stiffness
after inactivity)
If severe OA, pain can be present at night and at rest (late disease)
May also complain of limited function or disability as a result of joint affected
Joint swelling
Reduction in joint range of motion
Lower limb joints involvement may predispose to buckling/ giving way

Describe appropriate investigations for Osteoarthritis
-
Clinical assessment is critical
Laboratory Testing of Synovial Fluid may be used to rule out other diagnosis (this will require synovial
fluid to be clear and viscous with a WCC<2,000/mm3)
Radiography is used to confirm clinical suspicion and exclude other conditions
-
MANAGEMENT OF OSTEOARTHRITIS

List the non-pharmacological treatments of osteoarthritis
-
-
There is need to understand why we want to manage osteoarthritis in the patient to decide the
appropriate management plan
o Most patients present due to pain or functional impairment; as a result, management of
these patients will focus on relieving these symptoms
Non-Pharmacological treatments include:
o Education
o Exercise
o Weight Loss
o Appropriate Footwear

Describe the procedures involved in joint protection
-
Splints can be used to reduce load on joint, which will reduce damage, ease pain and improve
function
Exercise can strengthen muscles, which will improve joint function
-
19

Describe the role of physiotherapy in managing osteo-arthritis and its
components
-
Exercise can strengthen muscles, which will improve joint function
Physiotherapy will also improve function of the joint generally

Outline the surgical management of osteo-arthritis
-
Arthroscopic Surgery
o Theoretically can be used to treat meniscal tears or loose bodies
o However, there is no direct benefit to Osteoarthritis
Chondrocyte Implantation
o Effectiveness of Chondrocyte Implantation is unproven and is not indicated for osteoarthritis
Realignment Osteotomy
o Aims to shift the load away from the compartment with osteoarthritis
o This has been proven to reduce pain, improve function, slow progression and is particularly
used for younger and middle aged patients with flexible joints
Joint Replacement
o This is the last resort for patients with osteoarthritis after all other options have been
attempted (but with no success)
o It is preferred for older patients as they are less likely to require a repeated joint
replacement due to wear and tear of the prostheses (both as they live less years and have
lower levels of activity vs. younger people)
-
-
OVERVIEW OF DRUGS IN ARTHRITIS – NSAIDS & DMARDS

Explain the mechanism of action of NSAIDs
-
-
NSAIDs inhibit synthesis of prostaglandins (PGs) (which are inflammatory mediators)
o Mechanism of Action is through inhibition of Cyclooxgenase (COX), which is important for
converting Arachidonic Acid to Prostaglandins
NSAIDs also reduces potentiating actions of PGs

Describe the roles of prostaglandins in inflammation
-
Prostaglandins have the pro-inflammatory role of increase Vasodilation, which increases circulation
and influx of other inflammatory mediators

Describe the nature and incidence of side effects of different NSAIDs
-
Positive effects of NSAIDs include:
o Anti-inflammatory
o Analgesic
o Anti-Pyretic
Side effects include:
o Inhibition of Renal function (may cause renal toxicity)
o Inhibition of Platelet function (may cause bleeding)
o Inhibiting protection of Gastric mucosa (may cause GIT toxicity)
o Aggravate asthma in aspirin sensitive asthmatics (~5% of Asthmatics)
-

Describe the different profile of COX-2 selective drugs compared to typical
NSAIDs
-
COX-2 is important for inflammation, whilst COX-1 is important for Platelet function and Gastric
protection
COX-2 Selective Drugs should not have an impact on GIT and Platelets but still provide antiinflammatory effect (though still has same impact on renal function)
-
20
-
However, some COX-2 selective drugs have been associated with increased adverse Cardiovascular
Events

List the Disease Modifying Anti-rheumatic Drugs (DMARDs)
-
DMARDs improve long term outcome by slowing disease progression
Examples of DMARDs include:
o Methotrexate & Leflunomide (anti-metabolites)
o Sulfasalazine
o Chloroquine

Describe the mechanism of action of the DMARDs
-
-
Methotrexate is a folic acid antagonist (DMARDs binds to ( & inhibits) dihydrofolate reductase); this
inhibits the synthesis of:
o Thymidylate
o Purine nucleotides
Leflunomide will inhibit DNA / RNA synthesis and also block synthesis of Inflammatory T-Cells
Sulfasalazine mechanism is uncertain
Chloroquine decreases TNF-Alpha + other cytokines / molecules

List the side effects of the DMARDs
-
Methotrexate
o Bone marrow suppression
o Liver toxicity
o Pneumonitis
o Anaphylaxis
Leflunomide
o Gastro-Intestinal (e.g. Mouth ulcers, nausea/vomiting, diarrhoea)
o Skin rash and / or alopecia
o Minor infections (e.g. upper respiratory tract infection)
Sulfasalazine
o Gastro-Intestinal (e.g. anorexia, nausea)
o Anaemia
o Interstitial lung disease
Chloroquine
o Corneal deposits
o Retinal toxicity
o Time limited use
-
-
-
OVERVIEW OF MEDICATIONS IN ARTHRITIS – STEROIDS

List the rank order of potency of clinical corticosteroids
-
Dexamethasone
Prednisone
Cortisol

Describe the mechanisms of anti-inflammatory activity of corticosteroids
-
Transactivation (classical concept)  synthesis of effector (anti-inflammatory) proteins
Transrepression  switch off many inflammatory genes
Post genomic effects  destabilises pro-inflammatory mRNA
Activation of histone deacetylases (HDACs)  winding of DNA (no reading of inflammatory genes)
21

List the short term and long term side effects of corticosteroids
-
Short-Term Side Effects
o Weight gain
o Mood changes
o Increased blood glucose
o Hypokalaemia
o Transitory hypothalamic pituitary adrenal (HPA) axis suppression
Long-Term Side Effects
o Mineralocorticoid
 Na+ /water retention  leads to oedema and weight gain
o Glucocorticoid
 Osteoporosis
 Increased blood glucose
 Muscle wasting & thin skin
 Infection
 Cardiovascular (CV) risk (in patients with Iatrogenic Cushing’s Syndrome)
-

List the monoclonal antibodies, and their targets, used in treating
inflammatory arthritis
-
Infliximab – this targets TNF-Alpha (important inflammatory mediator)
o Other Anti-TNF-Alpha therapies include Adalimumab, Etanercept, Golimumab, Certolizumab
Tocilizumab – this targets IL-6
Rituximab – this targets CD20 on B-Cells
-
AUTOIMMUNE DISEASES

Explain the mechanisms of self tolerance
-
Tolerance is the specific inability of the immune system not to respond to self antigens
There are two key components to self-tolerance
o Central Tolerance = Deletion of auto-reactive lymphocytes in the primary lymphoid organs
 T cells: thymus
 B cells: bone marrow
o Peripheral Tolerance = Control of the activation of T & B cells in the secondary lymphoid
organs; lymph nodes & spleen
 T cells
 Need for co-stimulation CD28-CD80
 Control of expansion of T cells: Fas-FasL
 Inhibition by Regulatory T cells (Treg)
 B cells: need for T cell help

Describe the basis features of autoimmunity and its pathogenesis
-
-
Autoimmunity is the breakdown in Self Tolerance leading to immune responses against self antigens
Precipitated by interaction of environmental factors (e.g. infections or drugs) (60%) with a genetically
susceptible host (40%)
Pathogenesis of Autoimmune Diseases include:
o Induction (i.e. loss of self tolerance)
o Perpetuation of Autoimmune Disease (e.g. release of inflammatory cytokines)
o Chronic Fluctuating Phase (e.g. damage to tissue and dysregulation of cells) (there are
continued relapses and remission)
There is an autoimmune disease for every tissue in the body (e.g. rheumatoid arthritis in the joints)
Collectively they are the third commonest cause of morbidity and mortality

List the causes of autoimmunity
-
22
-
-
Autoimmune disease requires dysfunction in immune regulation, susceptible genes and the relevant
environment
Environmental triggers include:
o Antigens in microorganisms cross reactive with self proteins (molecular mimicry)
o Viral or other infections activate Dendritic cells expressing self Ag & breaks self tolerance
o Smoking is associated with development of anti-cyclic citrullinated peptide (CCP) antibodies
in RA
Genetic Triggers include variations of the following alleles of HLA:
o DR3 = 5x risk of SLE
o B27 = 90x risk of Ankylosing Spondylitis
o DR4 = 4x risk of RA

Describe the characteristics of autoimmune diseases and their classification
-
Autoimmune diseases are broadly classified as
o Organ specific (thyro-gastric cluster) where a single tissue is damaged (e.g. Addison’s
Disease)
o Non organ specific (systemic or lupus cluster) where multiple organs are involved (e.g. RA,
SLE)
Common characteristics of Autoimmune Diseases includes:
o Genetic predisposition
o Female preponderance
o Chronic fluctuating course (relapses and remissions)
o Occurrence with other auto-immune disease
o Presence of autoantibodies (e.g. rheumatoid factor)
o Lymphoid cell infiltration of tissues
o Response to anti-inflammatory and/or immunosuppressive drugs
Patterns of autoimmune connective tissue disease
o Antibody driven (presence of high titre auto-antibodies directed against self nuclear
components)
o T cell and cytokine driven (chronic inflammation driven by T cell and macrophage infiltration)
-
-

Outline the principles for diagnosing autoimmune diseases and the principles
of their treatment
-
Diagnosis of autoimmune diseases depends on:
o Confirming the presence of clinically significant disease
 Autoantibodies are useful, but they are common, particularly in elderly or healthy
relatives of patients with Auto-immune Disease
o Categorising the disease
 Is it RA, lupus, scleroderma, Sjögren’s syndrome, etc.?  these all have overlapping
clinical features
 Autoantibodies, rather than T cell tests, useful here
o Determining the extent of disease (e.g. local vs. systemic)
o Determining severity of disease
Principles of Therapy include:
o Determine extent of disease
o Anti-inflammatory drugs for mild/moderate disease (e.g. Prednisone)
o Immunosuppressive drugs for severe disease when no response to anti-inflammatory drugs
(e.g. DMARDs, Monoclonal Antibodies)
o Replacement when target tissue destroyed (e.g. Insulin in Diabetes)
o Removal of unwanted auto-antibodies or immune complexes by plasmapheresis
-
PATHOLOGY AND P ATHOGENESIS OF RHEUMATOID ARTHRITIS

Describe the acute joint changes in rheumatoid arthritis
23
-
-
Acute Joint Changes in RA include:
o Increased Vascular Flow (e.g. Oedema) (increases exudation of cytokines into joint)
o Endothelial Activation (increases exudation of cytokines into joint)
o Vascular Proliferation
o Replication of Macrophages and Fibroblastic Cells
o Increased thickness of Synovial Lining
Criteria for RA are:
o Morning Stiffness > 1 hour
o Arthritis of 3 or more joints
o Arthritis of hand joints
o Symmetrical Arthritis
o Rheumatoid Nodules
o Serum RF / ACPA
o Typical Radiographic Changes
o Note: Duration of Symptoms should be 6 or more weeks

Describe the chronic changes in the joint
-
Recruitment of cytokines
Remodelling responses
Reduced apoptosis of Synoviocytes
Proliferative response to Hypoxia
Synoviocyte Fusion
Development of Pannus
Erosion of Cartilage and Bone
Juxta-articular Osteopaenia
Subluxation of joints

Explain the mechanism involved in generation of pannus and destruction of
bone and cartilage
-
Pannus is defined as thickening synovial tissue
o As synovium thickens and proliferates, the joint actually fills with synovium and the
abnormal synovium (i.e. Pannus) migrates across the articular cartilage, eventually producing
erosions
o As pannus progresses, it can invade the bone and bone marrow, and destroy surrounding
structures like the joint capsule and tendons
o Within the Pannus:
 Both Type A (Macrophages) and B Synoviocytes (Fibroblastic) produce MMP (Matrix
Metalloproteinase) that eat away / erode cartilage (and hence results in an erosion
of the cartilage from the direction of the synovium)
 Type A Synoviocytes produce VEGF will stimulate Angiogenesis (i.e. production of
more blood vessels into the area))
 Various chemokines produced in the Synovium will encourage the influx of Th1,
Th17 and B-Cells, whilst other cytokines produced in the Synovium (e.g. IL-15, IL-18)
encourage their proliferation
 Hence, these T-Cells and B-Cells are not only being attracted / recruited to
the area but also proliferating in-situ (which will lead to the formation of
Nodules)
 Dendritic Cells will transport antigens to the B-Cells in the synovium, which will then
release antibodies (i.e. Rheumatoid Factor [RF] and ACPA)
 Other cytokines (e.g. IL-8) will attract additional Neutrophils into the Synovial Fluid
 However, these Neutrophils may produce various enzymes and oxidative
factors (e.g. reactive oxygen species) which further destroy the cartilage
24

List the systemic manifestations of rheumatoid arthritis and their incidence
rate
-
Occular
o Kerato-Conjunctivis Sicca (25%)
Respiratory
o Pleurisy and Effusion (50%)
o Diffuse Interstitial Fibrosis (28%)
o Crico-arytenoid Inflammation (25%)
Vasculitis (20-25%)
Entrapment Neuropathy (20%)
Pericarditis (3%)
Amyloidosis (~1-10%)
Haematological
o Felty’s Syndrome (2%)
-
-
URIC ACID METABOLISM AND MEDICATIONS

Outline the pathway for the metabolism and turnover of purines with
particular reference to uric acid
-
Uric acid is derived from the breakdown of
o Purine nucleosides e.g., adenosine, guanosine, inosine
o Purine nucleotides e.g., ATP, ADP, AMP, GTP, GDP, GMP, IMP
Salvage Pathways can prevent breakdown of Purine Bases from becoming Urate, and instead convert
them to Nucleotides
De Novo Pathways promote Nucleotide and hence Uric Acid Production
Uric acid is normally eliminated by renal excretion (which involves filtration, secretion and
reabsorption)
-

Explain how the abnormalities of this pathway or the excretion of uric acid
result in clinical disorders
-
Deficiencies in the salvage pathway (e.g. lack of required enzymes such as HGPRT) will result in
increased Uric Acid production
Similarly, problems with Excretion of Uric will increase levels of Uric Acid
Hyperuricemia may lead to acute attacks of Gout, Tophi and / or Renal Calculi

List the medications used in the management of these disorders and describe
their mechanism of action
-
Suppress acute inflammation
o NSAIDs
o Colchicine (inhibits phagocytosis via microtubule effect)
o COX-2 Inhibitors (e.g. Celecoxib)
Lower Uric Acid Levels
o Allopurinol (acts by inhibition of Xanthine Oxidase, which is needed for pathway of Uric Acid
synthesis)
o Uricase (converts Uric Acid to Allantoin [which is water soluble])
o Uricosurics (promote renal excretion by blocking reabsorption)
-
MUSCLE
PHYSIOLOGY OF MUSCLE

Describe the different types of muscle fibres and their means of contraction
25
-
Skeletal muscle Fibres contract via Excitation Contraction Coupling
Smooth Muscle Fibres contract via Cross Bridge Cycle

Explain the underlying mechanisms in excitation contraction coupling
-
Release of ACh (Acetylcholine) at the neuromuscular junction will trigger depolarisation of the muscle
fibre and the transmission of an Action Potential along the muscle fibre
Action Potential will travel through to the middle of the muscle fibre along T-Tubules (in addition to
along the surface) in order to enable quicker muscle contraction
Action Potential down the T-Tubule will trigger the opening of the SM Calcium Channel
o The SM Calcium Channel is coupled to the Sarcoplasmic Reticulum and will instigate opening
of the SR Calcium Channel (which causes the release of Calcium into the extra-cellular space
and hence contraction of the muscle fibre)
o Relaxation of the muscle will occur from the opening of the SR Calcium Pump which results in
Calcium re-entering the muscle fibre
-

Explain the trophic effects of nerves on muscles
-
Atrophy - muscles become smaller and thinner with disuse e.g. plaster cast, denervation
Hypertrophy e.g. weight lifters. Triggered by relatively small number of maximal contractions e.g. 10
max repetitions/day

List the patterns of denervation and re-innervation of muscles
-
Endurance (aerobic) training e.g. marathon runners
o Triggered by very large number of low force contractions per day. Causes fast fibres to
convert to slow fibres which are thinner, more aerobic and fatigue resistant
o Endurance training activates ‘slow-type muscle protein’ expression by activation of particular
transcription pathway
 Understanding the molecular basis of these pathways will be important in
understanding many types of myopathy
EXERCISE AND M USCLE

Explain the role of lactic acid, calcium release and reactive oxygen species in
muscle fatigue
-
Failure of calcium release causes fatigue
Lactic Acid is produced during synthesis of ATP from Glycogen
o Lactic acid theory suggests hydrogen ions will compete with Calcium to bind to Troponin
(which is normally required to produce force), which will result in fatigue
o Note: The Lactic Acid Theory is no longer viewed as accurate
Production of Reactive Oxygen Species (ROS) will increase during intense muscle activity
o It is believed that ROS will reduce the Calcium sensitivity of the muscle fibres resulting in
reduced force
-

Describe the cause and consequences of sarcomere stretching
-
Sarcomeres are unstable on the descending limb of the tension-length curve
These regions of damaged, stretched sarcomeres cause membrane damage, loss of intracellular
proteins and cause inflammation which is why muscles become sore & tender

Describe the process of muscle regeneration
-
Skeletal muscle contains a stem cell known as satellite cells
When muscle is damaged, stem cells are activated, perhaps by cytokines from invading inflammatory
cells
26
-
Activated stem cells form myoblasts which divide and fuse forming myotubes
Myotubes eventually repair and replace the damaged region of a muscle cell (regeneration)

Outline the role of dystrophin in muscle cell function
-
Dystrophin is a cytoskeletal protein which connects the contractile proteins to a group of proteins in
the cell membrane
o Dystrophic muscle is more susceptible to stretch-induced muscle damage (maybe dystrophin
reduces the membrane damage associated with over and understretched sarcomeres)
NERVE
NERVE STRUCTURE AND CONDUCTION

List the principle components of peripheral nerves:
-
The structure of the nerve is:
o Axon is surrounded by a Myelin Sheath that provides its insulation
o Myelin Sheath is surrounded a connective tissue layer called the Endoneurium
o Multiple Axons are surrounded by the Perineurium and form a Fascicle
o Multiple Fascicles are surrounded by the Epineurium and together they form a nerve

Explain the propagation of the action potential through non-myelinated and
myelinated nerve
-
Action potential generated via:
o Small rise in membrane potential to a threshold value triggers the Hodgkin Cycle (i.e. selfregenerating opening of voltage-gated sodium channels)
o Sodium channel inactivation due to prolonged depolarization
o Rapid repolarisation depends on delayed opening of voltage-gated potassium channels
o This sequence involves rapid reversals of the relative permeability of the neuron membrane
to sodium and potassium
The nerve impulse/action potential/spike spreads along the axon or nerve fibre
o Continuous propagation occurs in non-myelinated axons (e.g. some pain
fibres/axons/afferents)
 AP is continuously regenerated as is spreads along axon
 Continuous propagation is slow: 0.1 - 1 metres/second
o For Myelinated-Axons:
 Voltage-gated Na+ channels are concentrated at the axon hillock and the Nodes of
Ranvier
 The Hodgkin Cycle is triggered at one Node after another. This amplifies the signal.
 The thick myelin insulation of the Internode allows the local circuit current to
spread much further and faster than in non-myelinated fibres (e.g.~100m/sec)
 The signal travels passively & rapidly as a local circuit current between the Nodes
where it is regenerated.
-

List the ways action potential can be impaired
-
Demyelination / damage to myelin sheath
Ischaemia (i.e. interruption of blood supply, as this is needed for propagation of AP)
Physical damage to the nerve (e.g. cut, compression, bleeding in Epineurium, etc.)

Outline the processes for the maintenance of nerve function
-
Maintenance of connective tissue layers (e.g. Epineurium, Perineurium, Endoneurium) as they
provide:
o Structural support/protection for nerve fibres
27
o
-
-
Template and for nerve regeneration (extracellular matrix and basement membrane proteins
facilitate nerve growth)
 Damage to these layers hinders regeneration of the nerve fibres and slows or
prevents recovery
Removal of any blocks in propagation of nerves (e.g. external compression of nerve / blood vessels)
will result in quick recovery of nerve
If there is minor damage to the nerve (e.g. axon severance but endo-, peri- and epineurium
undamaged), the following process occurs:
o Distal stump undergoes Wallerian degeneration over several days (phagocytosis of the axon
and the myelinating Schwann.
o Proximal stump usually sprouts a new growth cone
o Growth cone of regenerating fibre re-innervates target tissue using endo-, peri- and
epineurium as template.
o Reinnervation will usually take a long time, as the axons grow at 1mm per day (maximum)
In contrast, if there is more serious damage (e.g. axon severance with damage to the endo- and/or
peri- and epineurium), then there are limited prospects for effective reinnervation

List the disorders of nerve propagation
-
Motor Neuron Diseases (e.g. demyelinating disorder)

Explain how compound action potentials of nerve and muscle can be
diagnostic tools
-
They can assess potential motor nerve damage, or a problem with the Neuromuscular Junction
In conjunction with history and clinical examination, this will assist with diagnosis of particular nerve
disorders (e.g. Carpal Tunnel Syndrome)
SYNAPTIC T RANSMISSION AND THE NEUROMUSCULAR JUNCTION

Describe the function of chemical synapses, using the neuromuscular
junction as an example
-
Chemical synapses are used to transit a signal from the presynaptic membrane / nerve to the postsynaptic muscle fibre
For example, ACh will be released from the presynaptic membrane and will activate the ACh
receptors at the post-synaptic membrane  this causes the receptor to be permeable to cations that
will depolarise the postsynaptic membrane ultimately resulting in a Hodgkin’s Cycle along the length
of the muscle fibre
-

List some of the major disorders associated with failure to neuromuscular
transmission
-
Lambert-Eaton Myasthenic syndrome (LEMS): autoimmune antibodies attack presynaptic voltage
gated calcium channels
Myasthenia gravis: autoimmune antibodies attack postsynaptic ACh receptor channels

Explain how electrical recordings can serve as diagnostic tools for disorders
of the neuromuscular junction
-
The electrical recordings can identify if the EPP (End Plate Potential) / mEPP (Miniature End Plate
Potential) are abnormal; this will provide an indication of whether there is a disorder of the
neuromuscular junction
o EPP amplitude = Quantal (i.e. mEPP) amplitude x number of quanta released
o The nature of the disorder (i.e. mEPP Amplitude vs. No. of Quanta) will assist in identifying
the type of disorder
28

Explain how anti-cholinesterase drugs are effective in myasthenia treatment
-
Cholinesterase inhibitor drugs will limit the time that Acetylcholinersterase spends near the ACh
receptors
o Acetylcholinersterase breaks down ACh and prevents it from binding with the ACh receptors
o Hence, Cholinesterase inhibitor drugs can be used to increase the level of ACh binding to ACh
receptors and hence mitigate Myasthenia Gravis
o Cholinesterase inhibitor drugs both prolongs and increases the amplitude of the EPP and
MEPP  the prolonged length of the EPP and MEPP will also assist in achieving the Action
Potential threshold as the amplitudes of the individual quantum are additive
CLINICAL ANATOMY OF THE PNS

The major features of the clinical anatomy of the peripheral nervous system
-
There are different patterns / types of Neuropathies
o Focal Neuropathies involves a single peripheral nerve
o Diffuse Neuropathies are the most common type of neuropathies and may result from
diabetes, chemotherapy, nutritional problems, hereditary, etc.
Key nerves (upper limb) to understand are:
o Median Nerve (***)
o Ulna Nerve (***)
o Radial Nerve (***)
o Musculocutaneous Nerve (**)
o Axillary Nerve (**)
Key nerves (lower limb) to understand are:
o Sciatic Nerve (and its branches) (***)
o Tibial Nerve (***)
o Common Peroneal Nerve (***)
o Femoral Nerve (***)
o Lateral Cutaneous Nerve of Thigh (**)
o Digital Nerve (esp. Great toe, medial nerve) (**)
-
-

The peripheral nerve syndromes that are most likely to come across in
clinical practice
-
Ulna Nerve neuropathy will result in wasting of the Interossei Muscles
o Complete loss of Ulna Nerve function may result in a ‘Clawed Hand’ due to the loss of
innervations to Interossei (resulting in extension of the MCP Joints) and Lumbricals (resulting
in flexion of the DIP and PIP Joints)
Median Nerve neuropathy will result in wasting of the Thenar Eminence
Radial Nerve neuropathy will result in finger and wrist drop
Injections in the Upper Arm could potentially hit the Axillary Nerve (as this wraps around the Neck of
the Humerus)
-
SKIN
PHOTOBIOLOGY UV AND THE SKIN

List the different wavebands within the solar spectrum
-
UVC
UVB
UVA 2
UVA 1
Visible
=
=
=
=
=
200 - 290 nm (sea level)
290 - 320 nm (erythemogenic)
320 - 340 nm
340 - 400 nm
400 - 760 nm
29

Describe the adverse and beneficial effects of ultraviolet radiation on the
skin
-
-
Beneficial Effects
o Vitamin D
o UV phototherapy (utilize immunosuppressive effect of UV)
o Photodynamic therapy
o Serotonin, circadian regulation, mood
o Prevention of autoimmune disease (TBC)
Adverse Effects
o Sunburn
o Skin cancer
o Photoageing
o Eye effects (e.g. photokeratitis, pterygium, cataract, macular degeneration (TBC), eyelid
tumours)
o Infections (via immunosuppressive effect of UV)

Describe the skin's main defense mechanisms against UV radiation
-
Melanin
o Scatter and absorbs UV
o Free radical quencher
o Note: Sunburn sensitivity is determined by melanin (and skin thickness)
Skin Thickening
o This is an important defence for pale people
o Epidermal > dermal thickening
o Single UVB exposure can double skin thickness
-

Explain how sunscreens work and their limitations
-
Sunscreens are generally better at preventing sunburn than immunosuppression
o They work by inhibiting UV from reaching the deeper layers of the skin
Broad spectrum sunscreens (UVB and UVA) are more immune protective
Limitations include SPF depending on:
o Sunscreen film thickness
o Spectrum of the UV source
o Skin type of the volunteers
o “Photo-decay” of sunscreen chemicals
o SPF doesn’t say much about UVA protection
Note: Real life” SPF is < half the laboratory SPF
-
-
PREVENTION OF SKIN CANCERS

Outline the prevalence of the various types of skin cancer
-
Lifetime risk in Australia: ~50%
>4 times as common as all other cancers combined
Continues to increase in older groups; ageing population; suboptimal compliance with sunscreens and
sun protection

List the risk factors and prevention strategies for skin cancer
-
Risk Factors include:
o Acute, intermittent UV exposure in childhood, adolescence and adulthood
o Some  risk with chronic UV
o Immunosuppression
o Defective DNA repair (e.g. Xeroderma pigmentosum)
30
-
o Genetic predisposition
o Pale skin
o Multiple bland or dysplastic naevi (i.e. lesions on the skin)
o Dysplastic naevus syndrome
o Sunburns
o Arsenic exposure
Prevention Strategies include:
o Protect skin immunity (from sunlight)
o Prevent DNA damage
o Enhance DNA repair
o Minimise UV exposure
o Sunscreens
o Chemoprevention

List the procedures for UV minimization
-
Avoid sunburn
Sunscreen
Shade (especially especially between 10 and 2 (11 and 3 in summer))
Protective Clothing (e.g. broad-brimmed hats, sunglasses, tightly woven clothing)
o Note: SPF of hats, shade ~ 3

Describe the sunscreen protection factor (SPF)
-
SPF = MED (Minimal Erythemal Dosage) of Protected Skin divided by MED of unprotected skin
This is the multiple of the time that can be spent in the sun to result in MED compared to no
protection
Note: SPF is a means of ranking products; this should not be used to calculate duration of “safe sun
exposure”
-

List the factors which affect SPF
-
Sunscreen film thickness
Substantivity (e.g. Perspiration; reapplication)
UV spectrum affecting skin
Skin type of the volunteers (e.g. darker vs. lighter skin)
“Photo-decay” of sunscreen actives

List the general measures to reduce the risk of skin cancers
-
Avoid above risk factors and incorporate above prevention strategies
Reduction in fat intake in diet
Avoid smoking
Reduce stress levels
Protect face from sun exposure

List the drugs which reduce the risk of skin cancers
-
COX Inhibitors
Retinoids (i.e. Vitamin A related)
DNA Repair Enhancers (e.g. T4N5 liposomes)
Nicotinamide

Describe the mechanism of action of nicotinamide in potentially reducing
skin cancer risk
-
Nicotinamide acts by replenishing cellular energy and enhances ATP-dependent DNA repair
31
o
o
DNA repair is highly energy dependent
UV depletes cells of energy when they need it most
OTHER
RADIATION SAFETY

TBA
-
There are two types of Radiation:
o Ionising Radiation (e.g. X-Ray, CT, Nuclear Medicine); this can be carcinogenic, teratogenic,
mutagenic and leukaemogenic
o Non-Ionising Radiation (e.g. MRI, UV Therapy, Lasers); Apart from UV, this is not
carcinogenic, teratogenic, mutagenic and leukaemogenic
Radiology displays anatomy (i.e. geography of the body), whilst Nuclear medicine displays function
(but doesn’t display the anatomy of the body)
o Techniques are available to overlay views of the anatomy and the function together to be
able to better utilise both pieces of information
The following are precaution measures for radiation:
o Minimise time of exposure
o Radiation shielding (e.g. lead apron)
o Longer distance from source
o Personal Monitoring of exposure
Radiation exposure should be minimised; hence, doctor’s should NOT over-order imaging
-
-
-
IMPACT OF CHRONIC ILLNESS

Outline the impact of chronic, progressive illness on psycho-social
functioning
-
-
Chronic pain and illness will affect bio-, psycho- and social- aspects (e.g. impact activity, mood,
occupation, functionality, etc.)
o The experience of pain and illness is a subjective experience, so consideration of these
different factors needs to be considered when evaluating a patient
o The experience of pain will be different from person to person (and even within one person
over time) when the sensory input is identical
Treatment should target as many of these different aspects as possible

Describe the major tasks of adaptation that follow onset or diagnosis
-
Patient needs to consider the impacts of the condition of the various aspects of their life
Patient should make adjustments to minimise these impacts and maximise their quality of life

Outline the key concepts in understanding and managing chronic pain
-
Chronic Pain conditions are common (~20% of people) but are amongst the most disabling health
problems
There are no real cures for some of these conditions, so instead treatment should focus on minimising
/ mitigating the different adverse outcomes from the condition
o Don’t always seek curative treatment, as this may not be possible and instead lead to
Iatrogenic problems (e.g. overuse of Opioids)
o Furthermore, this may set a false expectation for the patient that the doctor is responsible
for curing the problem (rather than the Patient taking responsibility for optimising their
quality of life and managing their pain)
-
SYSTEM
32
SHOCK – AN OVERVIEW

The definition and causes of circulatory shock
-
Circulatory shock is defined as a generalised inadequacy of blood flow throughout the body, to the
extent that tissues are damaged
Shock is usually due to an inadequate cardiac output (resulting from a reduced blood volume, or
diminished cardiac pumping ability), although occasionally may be due to an abnormal perfusion
pattern
There are four types of Circulatory Shock:
o Cardiogenic Shock – results from inadequate circulation of blood due to primary failure of
heart ventricles
o Vasogenic Shock – results from peripheral vascular dilation produced by factors such as
toxins that directly affect the blood vessels
o Neurogenic Shock – results from peripheral vascular dilation due to disruption of autonomic
pathways in the spinal cord
o Hypovolaemic Shock – results from reduction in blood volume (e.g. haemorrhage)
All the above four forms of circulatory shock are characterised by a profound fall in heart rate and
blood pressure
-
-
-

The physiological events by which blood loss leads to circulatory shock
-
There are two distinct phases in Hypovolaemic Shock:
o Compensatory Phase – maintenance of arterial pressure and perfusion to vital organs
 This occurs through vasoconstriction and increased heart rate
o Decompensatory Phase – sympathoinhibition resulting from significant fall in arterial
pressure and organ perfusion (occurs after ~15-20% blood loss)
During haemorrhage, vasoconstriction occurs in many vascular beds (except coronary and cerebral
beds, which have minimal sympathetic innervations)
-

The meaning of progressive and non-progressive shock
-
Non-Progressive Shock refers to the Compensatory phase
Progressive Shock refers to the Decompensatory phase

The pathological changes associated with shock, using the example of the
gastrointestinal system
-
Function is maintained in the compensatory phase
However, the shift to the decompensatory phase will see a reduction in blood pressure and blood
flow  this may lead to tissue degradation
BIOCHEMICAL SYNTHESES

Describe the capabilities and limits of biochemical syntheses in human
biology
-
The following can be synthesised:
o Key biochemical species e.g., some Amino Acids, some Fatty Acids
o Necessary precursors e.g., Purines, Pyrimidines, Ribose, Cholesterol, Porphyrins
o Energy-rich compounds for storage or export e.g., Fatty Acids, Ketone Bodies
o Provision of reducing power: NADH, NADPH, Glutathione
o Detoxification and excretion: Urea (for NH4+), mono-oxygenases, glucuronidation
The following CANNOT be synthesised (and must be supplied via diet):
o Essential Amino Acids
o Essential Fatty Acids
o Vitamins (except Vitamin D)
-
33

Explain the significance of vitamins
-
Vitamins (except Vitamin D) CANNOT be synthesised and must be provided via diet

Explain the difference between essential and non-essential amino acids and
fatty acids
-
Essential Amino Acids must be provided in the diet (as they cannot be synthesised)
Non-Essential Amino Acids can be synthesised
Essential Fatty Acids are those Fatty Acids that are unsaturated with double bonds beyond Carbon-9

Describe the strategies for fatty acid and cholesterol synthesis
-
Fatty Acid Synthesis requires Coenzyme A (CoA) and Acyl Carrier Protein (ACP)
o There is a chain of reactions required that use these inputs to develop a Fatty Acid
o The Fatty Acid produced from the Fatty Acid Synthesis can then be an input into the Fatty
Acid Synthesis process combining with Malonyl CoA to ultimately produce another fatty acid
two carbons longer (maximum chain length via this Fatty Acid Synthesis process if 16 carbons
[i.e. Palmitate])
Cholesterol Synthesis similarly CoA (via Acetyl CoA) to be performed; this synthesis also requires HMG
CoA Reductase (which is inhibited by Statins)
-

List the essential differences between saturated and unsaturated fatty acids
-
Saturated Fatty Acids have no double bonds, whilst Unsaturated Fatty Acids have double bonds
o Unsaturated Fatty Acids are normally liquid at room temperature

Explain the significance of cis and trans double bonds in fatty acids
-
Cis Fatty Acids (rather than Trans Fatty Acids) are found more commonly in nature and is the natural
form
o The kink in the Cis Fatty Acids makes it harder to crystallise and form solids; this keeps the
Fatty Acid liquid at body temperature which is more convenient to use and easier to
breakdown
o In contrast, Trans Fatty Acids are commonly used in processed foods as they preserve longer,
though they are less healthy

Describe the role of Pentose phosphate pathway in ribose and NADPH
synthesis
-
Pentose Phosphate Pathway is an alternative pathway for Glucose and will enable synthesis of Ribose
and maintaining Glutathione (GSH) in a reduced state
o This conversion into Ribose will produce several NADPH molecules

Describe the significance of glutathione in providing protection from prooxidants
-
Glutathione (GSH) reduce ROS species and hence provide protection from these pro-oxidants

Explain the consequences of glucose 6-phosphate dehydrogenase deficiency
-
Deficiency in this enzyme will inhibit the synthesis of NADPH, which is needed to convert GSH into the
reduced form that can provide protection from pro-oxidants
Hence, this deficiency will result in damage to cell membranes and Erythrocytes from the ROS species
-
34
BASIC BIOCHEMICAL TESTS – INDICATIONS AND INTERPRETATION

List the causes and low and high plasma sodium concentrations and low and
high plasma potassium concentrations
-
Causes of Low Plasma Sodium Concentrations
o Excessive Anti-Diuretic Hormone (Syndrome of Inappropriate ADH) (due to dilutional
hyponatremia)
o MDMA (i.e. Ecstasy)
o Addison’s Disease
o Diuretics (through removing water and sodium from body)
Causes of High Plasma Sodium Concentrations
o Diabetes Insipidus (due to high urinary water excretion)
Causes of Low Plasma Potassium Concentrations
o Diuretics
o Gastrointestinal K+ losses (e.g. Diarrhoea or Vomiting)
o Excessive Mineralocorticoid effects
Causes of High Plasma Potassium Concentrations
o Inadequate renal excretion
o Addison’s Disease
o Metabolic Acidosis
o Serious tissue injury
-
-

Describe the formation of bicarbonate and the causes of low and high plasma
concentrations
-
Bicarbonate is a key buffer for CO2, Carbonic Acid and H+ ion concentration in the body
o High (low) levels of CO2 will increase (decrease) concentration of Bicarbonate respectively
o High (low) levels of H+ ions will decrease (increase) concentration of Bicarbonate
respectively
These high / low levels of CO2 or H+ ions can result from Respiratory and Metabolic Acidosis /
Alkalosis
-

Describe the metabolic pathways for creatinine and urea and their excretion
-
Creatinine is secreted by the kidneys as a metabolic end product (arising from Creatinine Phosphate)
and hence its levels can be used to measure kidney function (in particular glomerular filtration of the
kidneys)
Urea is filtered AND secreted, so whilst it is not an excellent measure of renal function, it is a useful
measure of toxicity during chronic renal failure and the damage associated with the toxicity
o Creation and elimination of Urea is dependent on the function of the liver and kidneys (Liver
processes excess amino acids to generate Urea, whilst Kidneys eliminate the Urea)
o Urea and Creatinine by themselves are not toxic, but high levels are associated with other
molecules that are toxic
-

List the 3 main forms of calcium and factors which influence the plasma
calcium concentration
-
Three main forms of Calcium are:
o Calcium bound to Albumin
o Calcium ionised
 This ionised calcium regulates cellular and biochemical functions
o Calcium complexed with organic anions
Factors that influence Plasma Calcium Concentration include:
o Hypocalcemia
 Familial or sporadic hypocalcemia
 Hypoparathyroidism / resistance to parathyroid hormone
-
35
o
 Chronic renal failure
 Impaired vitamin D metabolism
 ‘Hungry bones’
Hypercalcemia
 Primary Hyperparathyroidism
 Malignancy
 Familial Hypocalciuric Hypercalcemia
 Vitamin D intoxication
 Granulomatous disease

List the tests to assess liver function
-
Total Protein Level (60-80g/L)
Albumin Level (40-50g/L)
Bilirubin (0-18 µM)
Enzymes (e.g. Aminotransferases [i.e. AST, ALT], Other enzymes [i.e. ALP, GGT])
INTRODUCTION TO N UCLEAR MEDICINE AND MUSCULOSKELETAL NUCLEAR
MEDICINE

Outline the principles of nuclear medicine in musculoskeletal disorders
-
Use of radioactive tracers to map biological processes (physiology and Pathophysiology) for the
diagnosis and treatment of disease
This involves ‘functional’ or ‘molecular’ imaging rather than focusing on anatomy or structure (i.e. XRay, CT)
-

List the features of Single Photon Emission Computed Tomography (SPECT)
-
SPECT gives depth information and removes superimposition seen on Planar Imaging
SPECT improves image contrast and allows better localisation of lesions

List the clinical applications of nuclear medicine in musculoskeletal disorders
-
Trauma  more specific than X-Ray at identifying fracture
Identify Sports injuries
Metastases
Infections
Identify cause of MSK Symptom
Arthritis (including extent and level of active inflammation)
Identify prosthetic complications (e.g. infection, loosening, etc.)
Metabolic bone Disease
Assessment of functional activity of radiologically detected lesion of uncertain significance

Explain the role of bone scans in assessing occult fractures
-
Bone scans can identify occult fractures not visible on X-Ray (e.g. Scaphoid Fracture, Femoral Neck
Fracture))
Almost all pathological processes in bone are associated with altered bone metabolism / altered
osteoblastic activity
Functional changes also occur earlier than structural changes  thus, bone scans are generally the
most sensitive means of detecting bone abnormalities
-

List typical sporting injuries
-
Talar Dome Fracture (i.e. Talus Fracture)
Fracture of Anterior Process of Calcaneus
36
-
Achilles Tendonitis
Avulsion Fracture of Navicular Bone
Shin Splints

Describe the role of bone scans in patients with cancer
-
-
Bone scans can be used to identify the stage / prognosis of cancers
o Bone turnover is increased in Cancer, and this can be identified by the Bone Scan
o Bone scan can screen entire skeleton and identify areas of Metastases
o Bone scan also more sensitive than other imaging techniques and can identify cancer earlier
than these other techniques
Bone scans can also identify cancer as the cause of MSK symptoms
Bone scans also useful for identifying MSK symptoms in patients with known cancer

Describe the role of gallium scans in musculoskeletal disorders
-
Gallium improves specificity of Bone Scans in identifying Osteomyelitis
o Gallium has uptake in inflammatory and malignant tissue
o Gallium will make it easier to identify sites of infection and / or cancer
GENERAL AND LOCAL ANAESTHETICS

New in 2014 – TBA
-
Local Anaesthetics (LA) block voltage-gated Na+ channels in nerves and other “excitable” tissue
o This will stop the transmission of signals through the nerve (by preventing depolarisation of
the nerve and transmission of the action potential)
o Hence, the pain signals from Nociceptors are not able to reach the Pain Cortex in the Brain
where the feeling of pain occurs
o Non-ionised forms of Local Anaesthetics can cross the cell membrane, though only the
ionised forms binds to the Sodium ion channel
Local Anaesthetic can access the binding site through a Hydrophobic or Hydrophilic Pathway
o If entering through the Hydrophilic Pathway, the Local Anaesthetic can only bind to the
sodium ion channel if it’s in use (i.e. pain is being felt)
o In contrast, if entering through the Hydrophobic Pathway, the Local Anaesthetic can only
bind to the sodium ion channel REGARDLESS if it’s in use (i.e. pain is being felt)
Local Anaesthetics are often used in conjunction with Adrenaline due to the vasoconstrictive
properties of Adrenaline (which will prolong the duration of action, minimise dosage required and
decrease toxicity [as local anaesthetic will not travel as far from the desired site of action])
General Anaesthetics target the CNS, whilst Local Anaesthetics target the PNS
o Four stages: (I) analgesia (II) excitement (III) surgical anaesthesia (IV) medullary depression
o Medullary Depression occurs if overdose occurs; this will results in respiratory arrest
followed by cardiac arrest
Effects of GAs that are important for medical treatments
o Analgesia (blockade of pain pathways)
o Anterograde amnesia (suppression of hippocampus, prefrontal cortex, amygdala)
o Immobility (depression of spinal motor neurons)
o Loss of consciousness (?)
The mechanism through which General Anaesthetic has its effect is not completely understood
(though several have been proposed)
-
-
-
-
-
ACTION OF OPIOIDS ON CELLS AND SYSTEMS

Describe the mechanism of action of opioids on neurons and the receptors
involved
37
-
All opium receptors are G- protein coupled receptors (i.e. Opium receptors activate a G-protein that
results in a signalling cascade in the cell)
Binding of Opioid to Receptor will:
o Change the conformation of the Opioid Receptor in a manner which activates a G-protein (by
changing the molecules bound to the alpha component of the G-protein)
o The activated G-protein will then send signals to their effectors (that are all inhibitory); they
will:
 Activate a K+ channel that result in the loss of Potassium in the cell  this will make
the inside of the cell more negative / less excited [and hence inhibited]
 Inhibit a Calcium 2+ channel that inhibit the entry of Calcium  this inhibits
neurotransmitter release
 Inhibition of Adenylyl Cyclase (AC), which catalyses conversion of ATP to cAMP 
this inhibits cAMP, which is a stimulatory second messenger in the cell
 Direct inhibition of Neurotransmitter release (i.e. GABA, Glu, etc.)
o This mechanism of action is the same for each of the three types of Opioid Receptors
o Opioid receptors will inhibit whichever cell they are attached to (e.g. GABAergic,
Glutamatergic, Dopaminergic), which inhibits the action of those cells
o There are three key Opioid receptors:
 Kappa receptors
 These produce analgesic effects
 Kappa-opioid agonists are rarely used due to the side-effect of dysphoria
and hallucinations
 Delta Receptors
 These produce analgesic effects (though less than Mu-receptors)
 Activation may produce seizures
 Not commonly used clinically as many of these receptors are believed to be
located within the cell (and hence are difficult to activate)
 Mu Receptors
 Most clinical opioid treatments (both agonists and antagonists) will act on
Mu-opioid receptors
 Mu-receptors are present in the areas of the brain responsible for
Analgesia (and Euphoria); they will also result in constipation, nausea,
respiratory depression, reduced cough reflex, tolerance and dependence

Describe the sites of action of opioids in the central nervous system and how
this results in the main and side effects
-
Opioid receptors are expressed through the brain / CNS;
o Receptors in PAG (Periaqueductal Grey) result in analgesia
o Receptors in Nucleus Accumbens result in the feeling of Euphoria / reward
o Receptors in Medulla responsible for side effects of respiratory depression, anti-tussive (i.e.
anti-cough), nausea, vomiting
o Receptors in GIT result in constipation

Develop an understanding of the endogenous opioid system
-
There are three main classes of Endogenous Opiates (i.e. Proenkephalin, Prodynorphin, ProOpiomelanocortin)
These endogenous Opioids will have an effect on different parts of the brain

Describe the role of opioids in the descending analgesic pathway
-
Opioids (e.g. morphine) will inhibit GABA release from the GABAergic Neurons in the PAG
o This reduces GABA release onto the Output Neuron and hence results in the output neuron
being more excited (as GABA is an inhibitor to the Output Neuron)
o This results in the Output Neuron increasing Glutamate release into the Medulla
38
o
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The Medullary Neurons send projections into the Spinal Cord, which triggers release of
Noradrenaline, 5HT (i.e. Serotonin) and Opioids, which acts to dampen the excitability of
Spinal Neurons and reduce the release from the Nociceptor
o Given the inhibition of the Nociceptor, there will be significantly less activation of the
upward pathway to the Somatosensory Cortex (where pain is felt)
o Hence, the use of Opiates will inhibit the feeling of pain
Another mechanism for Opioids to produce analgesia is to act on the Opioid receptors that are
directly on the Nociceptor terminals  activation of these Opioid receptors will result in inhibition of
the Nociceptors and hence less pain

-
Explain the pathway for opiate-induced euphoria

Describe the differences in properties and use of two opioid antagonists
-
Naloxone is a short-acting opioid antagonist used for reversal of opioid overdose
Naltrexone is a long-acting opioid antagonist that has been used for a long-time to treat alcohol
dependence, but is not effective at treating Opioids (as it does NOT reduce the craving)
The use of Naloxone vs. Naltrexone will be dependent on the particular Opioid resulting in overdoes
(given the length of effect of the antagonist should match the length of effect of the agonist)
-
Morphine will inhibit the GABAergic Neurons in the VTA
o This reduces GABA release (which is an inhibitor) onto the Dopaminergic neurons and hence
results in the Dopaminergic neuron being more excited
o This results in the Dopaminergic Neuron increases dopamine release into the Nucleus
Accumbens resulting in greater feeling of reward and euphoria
CLINICAL PHARMACOLOGY OF THE OPIATES

List the actions of opiates
-
Analgesia
Euphoria
Respiratory Depression

List the clinical uses of opiates
-
Pain Relief
Treatment of Dyspnoea
Treatment of Diarrhoea

Describe the metabolism of morphine
-
-
Bioavailability of ~20-30% with half-life of ~2-3 hours
Phase II drug metabolism involves another substance being added to the selected drug
o Glucaronic Acid will be added to Morphine as part of its metabolism; this can occur in two
different places result in M-6-G or M-3-G
Excretion of Morphine metabolites via kidneys (dose reduction required if impaired renal function)

Describe the metabolism of codeine and the enzyme involved
-
Codeine had advantage of higher bioavailability (~50%) than morphine (and hence lower doses
needed) and less euphoria than morphine, BUT has the disadvantage of being less potent (hence,
morphine is needed is pain is significant)
8% of Codeine is converted to Morphine (this may the driver of Codeine’s analgesia)
o This conversion results from the P450 isozyme “CYP 2D6”
o Genetic polymorphism of this enzyme may result in excessive or deficient conversion of
Codeine to Morphine
-
39

List the side effects of opiates
-
Respiratory Depression
Constipation
Dependence
Nausea
Vomiting

Outline the sustained release formulations of opiates
-
Sustained release of Morphine via Kapanol or MS Contin (these are coated tablets that delay release
of Morphine)
Sustain release of Oxycodone via Oxycontin formulation (~12 hours duration)
Methadone provides a slow release of Opiates with minimal euphoria (excellent for treating
dependence)
-
HEALTH LAW
HEALTH LAW 3 – CONSENT, KNOWLEDGE AND POWER

Outline the Guardianship Act 1987
-
Guardianship Act 1987 provides a hierarchy of people who could make decisions on the behalf of
others
o This act also sets the criteria / framework upon which such decisions should be made (e.g.
promote and maintain health and well-being of individual)

Describe the principles of this Act
-
To ensure that people are not deprived of necessary medical or dental treatment merely because
they lack the capacity to consent to the carrying out of such treatment; and
To ensure that any medical or dental treatment that is carried out on such people is carried out for
the purpose of promoting and maintaining their health and well-being
-

List the circumstances in which a guardian is to be appointed
-
Court appointed Guardian
Pre-agreed Guardian in circumstances individual lacks competence (e.g. coma, dementia, etc.)

List the limitations of guardianship
-
Guardian not approved to made end-of-life decisions and withdraw treatment (unless a special endof-life form of Guardianship has been approved)
Guardian must ‘promote health and well-being’ rather than looking for best-interests of patient 
this may be problematic when the two clash
-

Explain the problems arising from administering therapy without informed
consent
-
Medical procedures may be invasive and constitute battery / trespass without consent
Administering therapy without informed consent runs the risk of doctor being liable for negligence if
adverse outcome occurs (as patient was not fully aware of the risks and had their duty of care
breached)
HEALTH LAW 4 – SUBSTITUTE DECISION MAKERS
40

List the circumstances when substitute decision making is required
-
Where the individual lacks the capacity / competence to understand the decision, decisions need to
be made on the individual’s behalf (e.g. young child, mental issues, comatose, etc.)
In Australia, all children under 18 cannot refuse treatment by law (assume a clear threshold of age 18
to make refusal of treatment decisions)
-

Explain the Legislation wish relates to substitute decision making
-
Guardianship Act 1987 provides a hierarchy of people who could make decisions on the behalf of
others
o This act also sets the criteria / framework upon which such decisions should be
made (e.g. promote and maintain health and well-being of individual)
Children and Young Persons (Care and Protection) 1998 (NSW) also provides guidance regarding
substitute decision making for minors in emergency situations
-

Outline the objectives of the Guardianship Act
-
To ensure that people are not deprived of necessary medical or dental treatment merely because
they lack the capacity to consent to the carrying out of such treatment; and
To ensure that any medical or dental treatment that is carried out on such people is carried out for
the purpose of promoting and maintaining their health and well-being
-

List the range of “persons responsible”
-
The following hierarchy for ‘persons responsible’ in descending order is:
o Guardian (requires formal order to be made)
o Spouse (assumes relationship is close and continuing)
o Carer
o Close Friend / Relative

List the questions to ask an incompetent patient in need of treatment
-
Non-Emergency Treatments can be approved without the need to go to the Guardianship Tribunal
under listed circumstances (i.e. no substitute decision maker, treatment necessary and will most
successfully promote patient well-being, patient does not object to the treatment)
Other Non-Emergency Treatment will need to approved by the Guardianship Tribunal
-
PPD
TEAMWORK

Understand what a team is
-
...

Describe characteristics of effective healthcare teams
-
...

Understand the complexity of teamwork in healthcare
-
...

Describe some characteristics of effective leadership
-
...
41

Know ways that medical students can become team members
-
...

Describe the DESC script for resolving conflicts
-
...

Recognise that some group identification and resultant behaviours in
healthcare may be contrary to the patient’s interests
-
...

Understand major current structural limitations to good teamworking in our
healthcare system
-
...
PEER ASSESSMENT

Describe the reasons medical students need to learn to give and receive
feedback
-
Continued improvement of our skills is critical in Medicine
Medical Students will need to be able to provide feedback (to help other) and receive feedback (in
order to improve)
o Doctors are more likely to listen to feedback when it is from peers, so this is important
o Doctors are likely to face underperforming colleagues, so feedback is important to help them
Teamwork is a required competency for medical students. A necessary aspect of effective teamwork
is giving and receiving feedback
-

Describe the features of good and bad feedback
-
Good Feedback
o Specific
o Detailed (rather than one-line comment that could be misinterpreted)
o Direct
o Constructive
o Realistic
Bad Feedback
o Vague
o Irrelevant
o Overly personal
o Unhelpful
o Excessively Negative
-

Explain the SMS PBL Peer Assessment Process
-
...

List the Peer Assessment Instrument Items
-
...
PPD – GIVING AND RECEIVING FEEDBACK
42

Describe the reasons medical students need to learn to give and receive
feedback
-
Continued improvement of our skills is critical in Medicine
Medical Students will need to be able to provide feedback (to help other) and receive feedback (in
order to improve)
o Doctors are more likely to listen to feedback when it is from peers, so this is important
o Doctors are likely to face underperforming colleagues, so feedback is important to help them
Teamwork is a required competency for medical students. A necessary aspect of effective teamwork
is giving and receiving feedback
-

Describe the features of good and bad feedback
-
Good Feedback
o Specific
o Detailed (rather than one-line comment that could be misinterpreted)
o Direct
o Constructive
o Realistic
Bad Feedback
o Vague
o Irrelevant
o Overly personal
o Unhelpful
o Excessively Negative
-

Explain the SMS PBL Peer Assessment Process
-
...

List the Peer Assessment Instrument Items
-
...
SEMINARS
UPPER AND LOWER LIMB RADIOLOGY

TBA
-
ALWAYS check that the correct marker has been applied!!!
o ENSURE that the area of the body being examined / treated is the area with the problem (i.e.
do NOT operate on the left knee when the problem is the right knee!!!)
o CHECK that the right patient is being examined (i.e. the name on the X-Ray should
correspond to the patient being examined / treated)
During an exam, if asked to interpret an image without being provided a clinical history and /or
physical examination findings, always mention in the conclusion “to clarify by interpretation, I would
take a history and perform a physical examination”
There is anatomical variation between people and this needs to be considered when interpreting
images
o However, it is better to be conservative and note the variation as an “abnormality” rather
than indicating it is a “anatomical variation” (leave it to the Radiologist to decide if it is an
Anatomical Variation)
Radiologist will focus on key areas when examining an X-Ray  hence, assist the Radiologist by
articulating the key areas to assess (based on history and physical examination) rather than being
vague, as they may otherwise not review the area of interest
-
-
-
43
-
-
-
-
-
When describing a fracture that is displaced, describe the distal fragment in relation to the proximal
fragment
Remember that if a significant, large bone is fractured, then the trauma is likely to have caused other
damage too  hence, remember to review the surrounding structures for damage too as otherwise
problems may be missed
Surgical intervention is always needed if: Bone is sticking out of the skin (as this will be automatically
infected)
o Bone is sticking out of the skin (as this will be automatically infected)
o Fracture involves a joint space (as this joint will be unstable)
o Bone is in multiple fragments(i.e. ‘Comminuted’)
o Growth plate is affected
Surgical intervention for fractures below the wrist are dealt with by Plastic Surgeons (whilst
Orthopaedic Surgeons deal with fractures above the wrist)
The medical term for fixing a fracture into its correct position is ‘Reduction’
o ‘Closed Reduction; will NOT involve piercing the skin, but instead using tension and countertension to shift the fractured fragments in the anatomical position (this will be done under
anaesthesia)
o ‘Open Reduction’ refers to incisions and operation
 ‘Internal Fixation’ refers to insertion of pins, plates and /or nails to stabilise the joint
and can only be performed under Open Reduction
 Internal fixation will slow down bone healing process due to the presence of a
foreign body
First sign of shock is Tachycardia (i.e. higher heart rate), yet with normal blood pressure and
respiratory rate  there is a need to be careful as this sign can easily be overlooked!
Remember to always correlate interpretation of X-Ray with Clinical Findings
o For example, if strong, young, male rugby player presents with severe pain in elbow yet Xrays cannot identify a fracture, still treat as if there is a fracture in the interim and re-perform
X-Ray in another 2 weeks (as the fracture may only be evident with further time)
There are several “Red Flags” of lower back pain that will determine whether or not to X-Ray a patient
o Do NOT X-Ray or CT scan patients that lack any of these red flags
 This is due to 30% of patients possessing a disc abnormality that has no symptoms
 patients may then seek to have this corrected, yet it will have no impact of their
existing back pain
o The specific Red Flags are:
 Unintended Weight Loss (due to Cancer) Night Sweats (due to Infection)
 Pain that wakes up person at night (due to cancer and / or infection)
 Neurological deficit
 Loss of control of bladder and /or bowels (due to lesion in lumbar plexus)
 Any history of cancer
 Smoking
 Pinpoint tenderness over midline in back
BLOOD PRESSURE AND I TS FLUCTUATION

Understand the mechanical events of the cardiac cycle
-
The heart will pump in a particular manner, which is organised by a series of electrical stimuli (which
are triggered by the brain (i.e. the brain is the organ that controls blood pressure)
The different mechanical events in the cardiac cycle are:
o Phase 1 – Late Diastole
 Ventricles relax and blood passively flows into the Atrium and then into the
Ventricles
 At the end of this phase, the SA node depolarises (i.e. P wave) resulting in Atrial
contraction
o Phase 2 – Isovolumetric Contraction
 Mitral Valve closes and Ventricular Pressure rises (although ventricular volume is
constant)
-
44

-
-
-
-
Aortic Valve will open once the Ventricular Pressure rises above the Aortic Pressure
level
o Phase 3 – Systole
 Ventricular contraction / systole resulting in ejection of blood into circulation
 Ventricular contraction will end resulting in fall in Ventricular pressure (which will
result in closure of Aortic Valve)
o Phase 4 – Isovolumetric Relaxation
 All valves closed as pressure in ventricles rapidly declines (although Ventricular
volume remains constant)
o Phase 5 – Early Diastole
 Atrioventricular valves open and ventricles passively fill
 Note: Ventricles are >80% full via passive filling (i.e. prior to Atrial Systole)
During ventricular contraction, blood pressure in Ventricle will rise to the Systolic Blood Pressure
o Once the Aortic Valve closes, the end diastolic pressure within the Ventricle will fall to zero
(or even slightly below zero)  during this phase, the heart is sucking blood from the
Pulmonary Circulation
The heart received the majority of its blood supply in the Diastole Phase:
o This is due to when the heart constricts, the opening of the coronary arteries are hidden by
the Aortic Valve Leaflets whilst the coronary arteries are occluded by the closure of the
heavy muscular walls
Removal of the Atrial input / contraction (i.e. Atrial Fibrillation) will result in a loss of 20% of the
cardiac output
o Another way to lose 20% of cardiac output would be the slowdown of heart rate,
haemorrhage, decrease in total peripheral resistance (e.g. may be due to vasodilation)
Note: The following are definitions of terms related to the heart
o Lusitropy = the ability of the Ventricle to relax
o Inotropy = the ability of the Ventricle to contract
o Dromotropy = the speed at which electrical signal travels
o Chronotropy = the rate at which the heart contracts
o Note: Each of the above four features are individually controlled by the sympathetic nervous
system

Understand the principle of the Finapress method for measuring arterial
blood pressure
-
Finapress Device / Machine can be used to take continual measurements of Blood Pressure, ECG,
Cardiac Output, Mean Arterial Pressure and Heart Rate (in addition to several other metrics and
outputs [e.g. listening to Heart Sounds])
Finapress Device / Machine measures the arterial blood pressure through a ‘miniature
Sphygmomanometer’ (i.e. pump will increase pressure in the finger cuff until and electronically
measure the blood pressure via the changes in blood flow)
o Cuff pressure is automatically regulated to equal the arterial pressure
-

Observe the moment to moment fluctuations in blood pressure and heart
rate that occur under resting conditions and during simple manoeuvres
-
Exertion (which will trigger deep breathing) will result in large oscillations in MAP with each breath
Standing up will reduce blood pressure, but there is a compensatory increase in heart rate, such that
there is a net increase in cardiac output
o There is the pathology “POTS (Postural Orthostatic Tachycardia Syndrome)” that can cause
fainting that in common in young women

Understand the physiological mechanisms responsible for these fluctuations
-
Exertion triggers large oscillations in MAP due to inspiration of breath increasing venous return (by
creating a large negative pressure in the chest), which ultimately increases cardiac output and MAP
45
o
-
Inspiration will also activate pulmonary stretch baroreceptors, which will trigger increased
heart rate (and hence increased cardiac output and arterial pressure)
o In contrast, expiration of breath decreases venous return and heart rate, which ultimately
decreases cardiac output and MAP
Standing up results in shift of ~500-1,000mL of blood from the Thorax to the Lower Limbs
o This results in a reduction in venous return, and hence a reduction in blood pressure
o However, the baroreceptor reflex will be triggered resulting in increased heart rate and
peripheral resistance
IMPACT – MUSCULOSKELETAL DISE ASE IN THE COMMUNITY

Introduce students to some approaches to public health problems, including
measurement of health-related quality of life and economic appraisal of
interventions
-
Several of the main causes of disability globally are Musculoskeletal (e.g. Low Back Pain, Neck Pain,
Osteoarthritis, etc.) or psychological
o However, none of the main causes of death globally are musculoskeletal or psychological
problems
Musculoskeletal Diseases are still the biggest cause of disease in developing countries such as Uganda
SF-36 Health Survey is a patient-reported survey of patient health and is the most commonly used
methodology for measuring quality of life
Public health approaches can assist in quantifying the relative risk of particular risk factors (e.g. bone
mineral density) for Musculoskeletal conditions
Cost Effectiveness Analysis can be used to compare the costs and benefits of different options
o This involves calculation of the Cost per QALY (Quality-Adjusted Life Year)
o Cost per QALY = (Cost of Intervention – Cost of alternative) / (QALYs with Intervention –
QALYs with alternative)
-
TEAM APPROACH TO MUSCULOSKELETAL DISEASE

Introduce students to critical issues and current models for team
management of rheumatoid arthritis
-
Rheumatoid Arthritis is a chronic systemic inflammatory disease in which the brunt of the disease
activity is borne on synovial joints
o This disease will commonly occur bilaterally rather than unilaterally
o In a subset of patients, there are extra-articular manifestations of the disease
Rheumatoid arthritis is diagnosed based on the presence of a series of factors rather than one
particular sign
o This can consist of symptoms, laboratory results, aspects of history, etc.
o Note history and physical examination are the most valuable sources of information rather
than laboratory results (e.g. Surgeon makes 70% of decisions based on history, 25% of
decisions based on physical examination and 5% based on laboratory results)
Red flags that patient may be suffering from Rheumatoid Arthritis (or other form of Arthritis) include:
o Significant pain that persists over medium-term (as this should have resolved if due to
repetitive strain injury)
o Morning Stiffness
o Symmetrical nature of pain (i.e. bilateral)
o Multiple joints affected
Treatment involves a team approach including the patients, their family, GP, Rheumatologist,
Physiotherapist, Occupational Therapist and at times an Orthopaedic Surgeon
o Treatment will involve a delicate balance between rest and exercise, an adequate diet,
maintenance of ideal body weight as well as pharmacological intervention
o If managed appropriately, Rheumatoid Arthritis can be kept under control and generally
further joint damage prevented
-
-
-
46

-
-
-
-
-
-
-
-
-
Whilst there is no cure, a high proportion of patients can retain their quality of life,
remain in the workforce and be an active and productive member of society
The ‘ISBAR’ technique is used to handover patients from one person to another, and can be used as a
structure when writing a referral letter:
o Introduce yourself
o Situation explained
o Background of situation
o Assessment of patient
o Recommendation for patient
Other considerations to include in a referral letter include discussion of :
o Assessment conducted of patient
o Strength of relationship with patient
o Number of diagnoses considered and explored
Allied health professionals (e.g. physiotherapist, occupational therapist) will read the referral letter
from the specialists and consider their advice as they develop a treatment plan, but also conduct their
own assessment of the patient to ensure they identify all issues and select the most appropriate
treatment
o The relationship with the doctor is open and candid, and so any differences in opinion are
typically discussed and an agreed course of action determined
Key attributes doctors need to display:
o Listen to your patients
o Communicate with your patients
o Being present with your patients
Patient suspected of Rheumatoid Arthritis (or other form of Arthritis) should be referred to as a
Rheumatologist for the management of their disease to ensure they are provided the best and most
up-to-date expertise
o However, note the specialist and GP should then work collaboratively and communicate with
each other in order to provide the patient the best treatment (especially given GP is the first
point of contact for patient)
Physiotherapist will initially place patient on an exercise program to strengthen joints
o Note the exercise program will need to increase in steps / grades as the body / joints
progressively strengthens  increasing the intensity of exercise too quickly or too soon
could result in flare-ups and unnecessary pain
Occupational Therapy focuses on improving functional independence regardless of the type of
arthritis
o This can include splinting (including education of patient regarding use of splint), education
on joint protection techniques, education on minimising pain, installing adaptive equipment
(e.g. jar openers for jars with medicines)
o The outcome will be to make life easier for the patient, which increases their independence
and general wellbeing
Affliction by a chronic disease can be emotionally challenging and may need a level of counselling to
help them develop strategies to work through their issues at the time
o The particular type of counselling needed will be different depending on the particular
emotions of the patients (e.g. managing pain, grief, family issues, etc.)
Surgical intervention is only for the most severe cases where the patient is no longer able to walk /
function in their daily activities  in these circumstance, an arthroplasty or joint replacement will be
provided to improve the patient’s ability to function
CLINICOPATHOLOGY OF COMMON SKIN TUMOURS

Recognise the macroscopic appearance of some common skin tumours
-
Basal Cell Carcinoma
o Skin lesion (i.e. Basal Cell Carcinoma) can be described by:
 Site / Location = Skin on cheek
 Size
 Nodule = >5mm
47
-
-
-
 Papule = <5mm
 Shape = Dome-shaped
 Consistency = Firm
 Colour
 Surface Appearance = Pearly consistency with telangiectasia
 Edge = Well defined
 Relationships = No cervical lymph nodes involved
o Progression of Basal Cell Carcinoma (BCC) will involve growth and eventually ulceration
 BCC’s are quite aggressive / invasive and can eat through bones and cartilage
 However, BCC’s almost never metastasise (metastasis of BCC would be extremely
rare)
o Prognosis of cancer patient is much better if the tumour is well differentiated (rather than
undifferentiated)
Actinic Keratosis
o Skin lesion (i.e. Actinic Keratosis) can be described by:
 Site = Upper Back, Sun Exposed
 Size = Nodule > 5mm
 Shape = Horn-like
 Consistency = Firm – like a toenail
 Surface = Irregularly horny material; tough as toe nails
 Edge = Very well defined with NO pink reactive adjacent tissue
 Relationship = Review for nearby lymphodenopathy
Malignant Melanoma
o Skin lesion (i.e. Malignant Melanoma) can be described by:
 Site = Shoulder, Sun Exposed
 Size = 10mm [i.e. nodule]
 Shape = Irregular but rough oval; parts are macular [flat] and papular [raised]
 Consistency = Firm
 Surface = Pink and “black” variants
 Edge = Irregular; poorly defined with satellite nodules
 Relationship = No associated lymphodenopathy
o Some melanomas (i.e. amelanotic melanoma) will be pink rather than being pigmented (i.e.
black)
o Malignant melanoma tumour cells themselves often do not make significant melanin, but
this is typically produced adjacent to the tumour cells
o Prognosis for patients is better when tumour is in radial growth phase (i.e. macular lesion)
rather than the vertical growth phase (i.e. papular lesion)
Freckle
o Skin lesion (i.e. Flat Freckle) can be described by:
 Site = Arm, Sun Exposed
 Size = ~4mm [i.e. papule]
 Shape = Oval
 Consistency = Firm
 Surface = Uniform colour
 Edge
 Relationship
o Freckles will be due to hyperplastic Melanocytes (i.e. additional melanocytes)
o Raised freckles (i.e. compound freckles) will involve proliferation of melanocytes not only in
the epidermis, BUT ALSO within the dermis, which pushes the surface upwards

Understand how the microscopic features of these tumours are essential for
the diagnosis of these tumours, and how they assist in prognosis
-
There are characteristic microscopic features of the different types of skin tumours
o Understanding these features will enable accurate diagnosis of these tumours
The progression and hence prognosis of the tumour can be assessed by the level of their expansion /
growth microscopically
-
48
o
For example, tumours that have penetrated into the Dermis will have a worse prognosis
compared to tumours that remain in the Epidermis only
CLINICOPATHOLOGY OF DISEASES CAUSING BON E OR JOINT PAIN

Recognise the macroscopic appearance of some common diseases that cause
bone or joint pain
-
Osteoarthritis and Rheumatoid Arthritis
o Heberden’s Nodes refers to bony swellings (i.e. Osteophytes) on the Distal Interphalangeal
(DIP) Joints
o Osteoarthritis will display “Eburnation” in an X-Ray  this refers to the extremely whitish
area (sclerosis) on the X-ray and is indicative of hypertrophic change
o Osteophytes on the Cervical Spine may be indicative of Cervical Spondylosis
 This can cause both localised and radicular pain
o Rheumatoid Arthritis is a problem of the synovium rather than the bone directly
Paget’s Disease
o Paget’s Disease involves overexcitation of Osteoclasts resulting in excessive resorbtion of the
bone
 The Osteoblasts will increase bone forming activity to compensate, but cannot keep
up with the speed of the Osteoclast activity
 As a result, the Osteoblast will begin to form bone in a haphazard manner resulting
in the creation of Osteophytes
 Cortical Bone will be thicker but paradoxically weaker due to the
disorganised manner of bone growth (e.g. curved, bow-legged bones, loss
of trabelucar pattern)
Osteosarcoma (i.e. Bone Cancer)
o Codman’s Triangle is common in Osteosarcoma; results from the periosteum growing up due
to the tumour growing underneath it
o Tumours can result in pathological fractures
o There is a highly level of anaplasia (especially hyperchromatic nuclei and multinucleated
cells)
Gout
o Gout results from the build-up on Uric Acid crystals in the joint
 Higher cell turnover will result in the release of purines, which increase the level of
Uric Acid
o Patients are extremely sensitive to touch
o Symptoms include erythematous and swollen hallux (i.e. 1st metatarsal-phalangeal joint)
o Tophi involve the depositing of crystals in joints, cartilage, bones and other spaces in people
with high levels of uric acid
 The presence of Tophi are characteristic of gout
 However, note Tophi can occur both in joints but also other areas that have
cartilage but are not a joint (e.g. ears)
o Gout are a destructive arthropathy and will destroy bone  inspect for extraarticular
erosions of bone and swelling
Osteomyelitis
o Diabetic Ulcers can be a sign of underlying Osteomyelitis
o Investigate with an X-Ray to look for bone damage  this can be used to diagnose
Osteomyelitis
o Antibiotic treatment will not be very effective for Osteomyelitis
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Understand what roles the microscopic features of these disorders play in
the diagnosis of these disorders
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There are characteristic microscopic features of the different diseases causing bone pain
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For example, Gout may involve the presence of Giant Cells (which attempt to phagocytose
and eliminate the crystals), as well as the creation of Granulomas (which has the side effect
of destruction of the joint / cartilage)
For example, Paget’s disease will reveal a thicker, but disorganised bone structure (e.g. loss
of trabecular pattern)
INTRODUCTION TO EBM
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Understand the patient-doctor interaction
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Evidence-Based Medicine is not a case of doing exactly what the evidence says, but rather
incorporating a range of factors (i.e. Patient Factors and Clinical Factors) in addition to the evidence to
determine the best course of action
o Patient Factors include consideration of patient values and preferences (e.g. importance of
quality of life vs. length of life), co-morbidities and severity of disease
o Clinical Factors include consideration of clinical skills, knowledge and experience

Formulate a series of questions that may be answered using the best
available research evidence
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The PICOT format is useful for structuring the particular question / terms to search; this involves
structuring the question based on:
o Population
o Intervention
o Comparator
o Outcome
o Type of Study (this depends on the type of research question)
Outcomes can include recovery, pain, cost, quality of time, etc.
The level of specificity for the question is important as too broad will result in too many results, whilst
too specific will result in insufficient results
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HOW TO USE AUTO ANTI BODIES FOR DIAGNOSIS
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TBA
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There are a range of different auto-immune diseases that may result from loss of self-tolerance:
o Systematic Lupus Erythematosus (SLE) is characterised by multiple autoantibodies and a
range of symptoms (e.g. arthritis, malar rash, photosensitivity, serositis, etc.)
o Rheumatoid Arthritis (RA) is a chronic, systemic inflammatory disease  symptoms will
include not only arthritis, but also serositis, vasculitis, nodule formation, etc.
o Sjogren’s Syndrome is a systemic autoimmune disease mostly directed at exocrine glands 
symptoms will include sicca, arthralgia, myalgia, etc.
o Mixed Connective Tissue Disease (MCTD) is a systemic autoimmune disease that overlaps
Myositis, Scleroderma, SLE, RA symptoms will include sicca, arthralgia, sclerodactyl (i.e.
tightness of skin)
o Scleroderma is a systemic autoimmune disease characterised by progressive dermal fibrosis
and vascular alterations
 There are two types – CREST (Calcinosis, Raynaud’s, Oesophageal Dysmobility,
Sclerodactyl, Telangiectasia) and Generalised (CREST changes but more widespread,
renal involvement, vascular obstruction)
There are two type of autoantibodies:
o Markers – used for Diagnosis, but do not cause disease
o Pathogenic – causes of disease
‘Transplacental Transfer of Disease’ refers to the transfer of autoantibody from the mother to the
child through the placenta
o This is strong evidence that the Autoantibody is pathogenic and causing disease
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Autoantibody tests are not black vs. white, but rather have a degree of subjectivity that requires
interpretation
o Each test will have a specific sensitivity and specific specificity depending on the particular
disease
 The specificity and sensitivity of the test will also depend on the testing
methodology undertaken by the laboratory
 This is due to there not being a universal standard for these tests and different
laboratories using different standards
Doctors may prefer initial tests for diagnosis to be highly sensitive (in order not to miss any
conditions), but may prefer tests for prognosis to be highly specific (to ensure management /
treatment plan is appropriately tailored)
ANA (Anti-nuclear Antibodies) is a useful screening test for patients suspected of having a connective
tissue disease
o This involves applying patient’s serum to a slide which contain a series of nucleus antigens
and then washed
o If the patient’s serum contains an autoantibody, it will bind to the nucleus antigen
o Fluorescent material that will bind to antibody is then applied to slide; if the antibody still
remains, it will bind to the fluorescent material
o The fluorescent material (and its connected autoantibody) are then identified based on the
fluorescence
o Different diseases will have different distributions of ANA Fluorescence (as the antibodies of
different disease target different parts of the nucleus) (e.g. Homogenous, Membranous,
Speckled, Centromere, Nucleolar); for example:
 Membranous – SLE
 Homogenous – SLE, Drug-induced Lupus
 Speckled – SLE, Sjogren’s, MCTD, Others
 Nucleolar – Scleroderma, SLE
 Centromere – CREST (i.e. Scleroderma)
Interpretation of ANA tests involve the patient serum being diluted until the ANA test becomes
negative
o The higher the dilution requires, the stronger the auto-antibody levels and the greater the
likelihood of the presence of the autoantibody being significant (i.e. indicative of an
autoimmune disease)
 Increasing the level of dilution (i.e. higher titres) will result in a reduced number of
false positives (albeit some small amount still remaining)
 However, there is a greater risk of false negatives the higher the titre
 Hence, there is a trade-off / inverse relationship between sensitivity and specificity
o Hence, interpretation of ANA tests contain subjectivity, as there is a spectrum of normal
levels (rather than being a definitive, specific level)
Following a positive ANA test that suggest the presence of an auto-immune disease, ENA tests are
conducted to both confirm the presence of an autoimmune disease and provide specificity on the
type of autoimmune disease
o Positive ANA test does not mean anything by itself; instead, any result should be further
investigated with ENA tests and correlated clinically to be able to diagnose a specific disease
ENA tests involve extracting proteins from particular areas of the nucleus and testing for antibodyantigen reaction for each of these particular areas
o Examples of ENAs include SSA, SSB, Sm (Smith), dsDNA, Histone, Scl-70, RNP, etc.
 SSA – SLE, Sjogren’s
 SSB – SLE, Sjogren’s, RA, Neonatal Lupus
 Sm – SLE
 dsDNA – SLE
 Scl-70 – Scleroderma
 RNP – MCTD, SLE, Other autoimmune diseases
The existence of Autoantibodies does NOT mean there is a disease, but it does indicate a heightened
risk of contracting the relevant autoimmune disease in the future
Anti-Neutrophil Cytoplasmic Antibody (ANCA) is a screening test for specific types of Vasculitis
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The different fluorescence patterns of ANCA can be used to distinguish between the
different types of Vasculitis (i.e. Granulomatosis with Polyangiitis vs. Churg-Strauss Syndrome
vs. Microscopic Polyangiitis); for example:
 Classical ANCA – Granulomatosis with Polyangiitis
 Perinuclear ANCA – Churg-Strauss Syndrome, Microscopic Polyangiitis,
Granulomatosis with Polyangiitis, Drug-induced vasculitis
Direct Immunofluorescence detects antibodies and complement deposition within tissue themselves;
this is particularly useful in kidney disease and vasculitis
o For example, this can be used to detect Goodpasture’s Disease (which is a rare condition that
has a high risk of renal failure)
Autoantibodies to Gliadin are non-pathogenic marker autoantibodies for Coeliac Disease
o Other antibodies identified via serological testing (e.g. TTG Antibody, EMA Antibody) can also
identify the presence of Coeliac Disease
Rheumatoid Factor and Anti-CCP are both markets of Rheumatoid Arthritis
o Anti-CCP test is much more specific than Rheumatoid Factor tests for Rheumatoid Arthritis
(yet has similar sensitivities)
Antiphospholipid Syndrome can be detected via presence of Anticardiolipin (ACL) or Lupus
Anticoagulant (LA)
Important to consider the risk of false positives; hence, only run tests when there is an initial high
level of clinical suspicion
o If the initial test is positive, follow up with more specific antigen tests
STUDY TYPES
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Introduce students to the concept of study designs
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There are different ways / designs to conduct a study
o The optimal study design will vary depending on the type of question being asked
Experimental Analytic Studies involve the experimented manipulating the type of treatment received
by the sample
o In contrast, Observational Analytic Studies do not assign the treatment received by the
different groups but rather this occurs by chance (and this is then measured by the
experimenter)
The difference between a Randomised Controlled Trial (RCT) and Cohort Study involves whether the
experimenter is specifically manipulating the treatment / intervention received by the sample or
whether this occurs by chance
o Case Control Study differs from Cohort Study in that sample is selected based on patients
with a disease / outcome and reviewing backwards (i.e. retrospectively) to identify the
particular interventions / exposures experiences by the sample
Analytic Cross Sectional Studies involve measuring the Outcomes and Exposures simultaneously (or
approximately simultaneously)
o This is useful for assessing the quality of a diagnostic test
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Outline the strengths and weaknesses associated with the varied study
designs used in evidence based medicine
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Whilst Randomised Controlled Trials (RCTs) provide the best quality evidence of Aetiology, they may
not always be practical or ethical; in this event, other types of studies will be used (e.g. Cohort Study,
Case Control Study, Systematic Review)
Well designed Cohort Study is the best study to provide evidence on questions regarding Prognosis
Analytic Cross Sectional Studies are the best study to provide evidence on questions regarding
Diagnosis
o Randomised Controlled Trials (RCTs) can also be used (especially in the context of Screening
Tests, as this will assist in understanding whether correct diagnosis is making an impact on
the patient’s outcome [rather than simply identifying disease even if they are not having an
impact on the patient])
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Cross-Sectional Studies (e.g. survey to patients) are the most useful study for answering questions
regarding Frequency
Randomised Controlled Trials (RCTs) are best used for evidence of the best Therapy, but this is not
always possible
Advantage of Cohort Studies (vis-a-vis RCTs) is that multiple exposures can be measured (as only a
single exposure is tested in an RCT), as well as being easier and cheaper to conduct
o However, the disadvantage of Cohort Studies is there may be significant differences between
the cohorts other than the intervention, which causes a difference in outcomes
o Furthermore, Cohort Studies are difficult to conduct for rare diseases as it may be difficult to
gather sufficient patients / data to develop statistically significant results
Case Control studies are a less robust study methodology compared to Cohort Studies and RCTs as it
requires patient to have quality recall and it may be such that the outcome (e.g. lung cancer) had
already occurred prior to the particular intervention / exposure being assessed
o Furthermore, there may be selection bias in the control group that distorts the results and /
or the presence of confounders
o However, the advantages of Case Control Studies include being quicker / cheaper, enable
research to be conducted on rare diseases and those diseases with a long time lag between
risk exposure and disease onset
Advantage of RCTs is that they control for both known and unknown confounder (as the only
difference between the two groups is the exposure being examined)
o Potential Confounder is a variable that has an association to both the exposure factor and
also the outcome factor
o This may mask a real association between the exposure and outcome OR falsely create an
association between the exposure and outcome
Disadvantage of all RCTs are that patients participating is trials tend on average to do better than
those patients who don’t participate; this may be due to:
o Better care / conditions provided to patients who are under examination
o Patients who are more willing to participate in these trials are more effective at taking care
of their health
Consistency of intervention can be difficult to obtain in surgical interventions (as approach /
technique may be slightly different for each patient)
Use of an inappropriate comparator may lead to misleading interpretation of results of study
IMAGING THE MUSCULOSKELETAL SYSTEM
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TBA
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When conducting a joint examination, remember to ALWAYS conduct a examination bilaterally (i.e.
BOTH the side with pain / problems AND the side without the pain)
The four characteristic radiological symptoms of Osteoarthritis are:
o Subchondral Cysts (i.e. small, darkened areas in the bone near the surface of the bone that
contain synovial fluid)
o Subchondral Sclerosis
o Osteophytes; and
o Reduced joint space
The most appropriate treatment for the patient should consider not only the radiographic images /
damage to the joint, but also the functionality of the patient
o For example, if patient is mobile and living with minimal pain, then surgical treatment would
not be appropriate even if there is a lot of damage per the radiographic
When discussing the wrist, use the terms ‘Radial’ / ‘Ulna’ rather than lateral / medial to describe
direction (as medial and lateral will be different depending on whether the forearm is pronated /
supinated)
Severe fractures would require significant pain relief
o Morphine would be preferred rather than Paracetamol, but this may not be appropriate if
there are neurological or hypotension concerns (as this will affect the GCS score)
o Alternatively, a Nerve Block can be used instead to provide pain relief
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Remember to conduct assessment of other areas (e.g. Abdomen, Pelvis) too instead of only focusing
on the immediately visible problem only
o Internal Bleeding in these areas could result in rapid death of patient
o The biggest risks (i.e. problems that can cause death) should always be reviewed and
screened for
Patient experiencing significant pain (despite analgesic provision) in an Orthopaedic Ward should
never be taken lightly due to the risk of Compartment Syndrome
o Compartment Syndrome refers to a build-up in pressure in one or more of the
compartments of a limb
 As a result, there is compression of vascular supply; this will result in occlusion of
the supply to the muscles ultimately resulting in death of the muscle
o Compartments are surrounded by Fascia, which is NOT flexible
 The space available in the compartment cannot increase / adapt to an increase in
the contents [e.g. blood]) (the attempted stretching of the Fascia due to the
increase in pressure within is the cause of the significant pain)
 Tibial Fracture can result in loss of 1L of blood, whilst Femoral Fracture can result in
loss of 1.5 to 2.0L of blood
 Blood entering the compartments can increase the pressure resulting in
Compartment Syndrome
 The lower leg (i.e. Tibio-Fibular area) has the highest risk of Compartment Syndrome
o Signs of Compartment Syndrome include:
 Pain out of Proportion (which is diagnostic)
 Significant pain on Passive Dorsiflexion
 Tension in Compartment
o The 6P’s of Compartment Syndrome are:
 Pain
 Parasthesia
 Pallor
 Paralysis
 Pulselessness
 Poikilothermia (i.e. coldness)
 NOTE: Pain will be the first sign (prior to the other 5P’s appearing); waiting for the
other 5P’s will be too late
o The definitive management for Compartment Syndrome is Decompression (i.e. cutting open
the compartment)
 Compartment Syndrome treated within 4 hours will result in full recovery, whilst
damage is irreversible if Compartment Syndrome not treated within 8 hours (as the
muscle will have been without vascular supply for too long by then)
o Note: Fracture of a Tibia and Fibula make Compartment Syndrome less likely as it increases
the likelihood of having pierced the Fascia membrane, but there is still a chance the Fascia
was not disrupted
All trauma patients will receive a chest and pelvis X-Ray; if there is any neck disruption / concerns, CT
or X-Ray the neck and brain
o Emergency Physicians could also conduct a FAST Scan of the Abdomen (i.e. quick bedside
ultrasound) to look for free fluid (and hence blood) in the abdomen
Confirmation of the Diagnosis of Septic Arthritis can be done by aspirating the joint and reviewing for
the presence of pus and / or white cells (rather than synovial fluid)
o Treatment of Septic Arthritis involves opening up and washing out the joint, followed by
treatment of IV antibiotics for several weeks
‘Monteggia Fracture’ involves a fracture of the proximal third of the ulna and dislocation of the Head
of the Radius
o Such a severe fracture (with a sharp end of the fragment of the Ulna) with the neurovascular
problem (i.e. capillary refill ~5 seconds) will require urgent surgery
o Patient should have the fracture immobilised in a half-cast, provided analgesia and sent to
surgery as soon as possible
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Neurovascular supply should be assessed every 2 hours until surgery given the high
risk of neurovascular problems
 The patient should also be monitored post-surgery as there may be bleeding into
the compartment and hence there is a risk of Compartment Syndrome
Severe trauma patients cannot be trusted to maintain their airway (there are several reasons why this
may occur) and hence are intubated
o Assume that patients with an Endotracheal Tube and under Mechanical Breathing are both
anaesthetised and paralysed
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