Enters thigh
- midway between ASIS and pubic symphysis
- in femoral triangle
- NAVY (nerve / artery / vein / Y fronts)
- in femoral sheath with femoral vein (transversalis fascia and psoas fascia)
- femoral nerve outside sheath / under the iliac fascia / lateral
Femoral triangle
Anatomy
- inguinal ligament superiorly
- medial border sartorius laterally
- adductor longus medially
- floor is iliopsoas, pectineus and adductor longus
Femoral vein
- enters thigh posterior to femoral artery
- comes to lie medially
- receives great saphenous vein anteromedially
- in femoral triangle / just below femoral sheath
Femoral artery
- 4 branches under inguinal ligament
- superficial circumflex iliac
- superficial epigastric
- superficial and deep external pudenal
Enters adductor canal / subsartorial canal
Anatomy
-sartorius is roof
- floor is longus then magnus
- contents artery, vein and saphenous nerve
- vein comes to lie posterolateral
- artery always between vein and nerve
Saphenous nerve
- exits between sartorius and gracilis
- pierces fascia
- runs with great saphenous vein
Surgical approach
- medial thigh incision
- reflect sartorius medially
- divide fascial roof
Artery to thigh muscles
- exits laterally at termination of femoral sheath
- 3-4 cm distal to inguinal ligament
- arises from lateral side
- passes between pectineus and add longus
- runs behind longus
- runs down on adductor brevis and magnus
- gives 4 perforating branches
Perforators
- pass backwards through adductor magnus
- one above, second through, third and fourth below adductor brevis
Lateral circumflex
- lateral side of profunda
- passes laterally between branches of femoral nerve
- under sartorius and rectus
A. Ascending branch
- runs up between sartorius and TFL
- on vastus lateralis
- must be ligated in Smith Petersen approach
- supplies trochanteric anastomosis
- ends ASIS
B. Transverse branch
- passes across v. lateralis to wrap around proximal femur and supply cruciate anastomosis
C. Descending branch
- descends in groove between v. lateralis and intermedius
- travels with nerve to v. intermedius
Medial circumflex
Arises
- medial side profunda
- passes backwards between pectineus and psoas
- runs to back of femoral neck
Deep branch
- runs along inferior border of obturator externus
- emerges between obturator externus and quadratus femoris
- then runs over tendons of conjoint and piriformis
- supplys femoral head via posterior and superior femoral neck branches
Other branches
- anterior / posterior / transverse and trochanteric
Boundaries
Superior: biceps laterally with semitendinosis / semimembranosus medially
Inferior: medial and lateral gastrocnemius
Floor: knee joint and capsule, popliteus
Anatomy
- deepest structure throughout
- enters deep and medial
- medial to femur via adductor hiatus
- bows laterally
- exits posterolateral to tibial nerve under fibrous arch of soleus
- returns to medial side
Popliteal vein
- always between artery and nerve
Divisions
- lower border of popliteus
- usually into anterior and posterior tibial artery (gives peroneal as a branch)
- sometimes into anterior and peroneal artery (
- sometimes into anterior / posterior and peroneal artery
Relations leg
- runs down on tibialis posterior behind deep intermuscular septum
- travels with tibial nerve
- at times between FHL and FDL
- gastronemius and soleus superficial
- gives peroneal artery as a branch
Relations ankle
- runs back of tibia and ankle joint to tarsal tunnel
- runs in groove behind medial malleolus between T posterior and FDL with tibial nerve
- passes deep to abductor hallucis and divides into medial and lateral plantar arteries
- found between first and second layer of the foot
- lateral plantar forms plantar arch by uniting with deep branch of the dorsalis pedis
Origin
- usually branch of posterior tibial
- 2.5 cm below popliteus
Relations
- runs along medial aspect fibula
- between FHL and T posterior
Origin
- lower border of popliteus
Relations leg
- passes between two heads T posterior
- passes through aperature of interosseous membrane
- descends on interosseous membrane
- initially between T anterior and EDL
- eventually is crossed by EHL and crosses ankle between EHL and EDL
- runs with the deep peroneal nerve
- becomes dorsalis pedis under extensor retinaculum
- runs to interval between 1st and second MT
Origin
- on right arises from brachiocephalic trunk behind right sternoclavicular joint
- on left arises from the arch of the aorta
Ends
- outer border first rib as axillary artery
First part
- origin of artery to medial aspect scalenus anterior
- on right arches above the clavicle / lies on the pleura / RLN wraps about it
- vertebral artery / thyrocervical trunk branches
Second part
- behind scalenus anterior
Third part
- from lateral scalenus anterior to outer border first rib
- behind subclavius and the subclavian vein
- trunks of brachial plexus around it
Access / Proximal control
- must remove central portion clavicle
Origin
- Outer border first rib
Ends
- lower border teres major to become brachial artery
Relations
- axillary vein medial and anterior
- covered by P major and minor
Second part
- behind P major
- cords of the brachial plexus suround the second part
Third part
- below P major
- medial to conjoint tendon
- median nerve is lateral, median branch median crosses artery
- ulna nerve is medial
Branches
- thoracoacromial
- subscapular
- anterior and posterior circumflex humeral
Access / Proximal control
- divide P major from humerus
- divide P minor from medial coracoid
- take conjoint tendon from coracoid / coracoid osteotomy
Origin
- lower border tendon T major
Ends
- division radial and ulna at elbow / neck of the radius
Relations
- initially medial to humerus
- at elbow is midpoint between 2 epicondyles
- 2 venae commitantes
- basilic vein runs with it in upper part of arm / is superfical to fascia distally
- medial nerve is medial to nerve in lower part of arm
- crossed by lacertus fibrosis
- biceps tendon medial
Branches
- profunda brachii to run with radial nerve
- superior and inferior ulna collateral
Origin
- cubital fossa between BR and PT
- continuation of the brachial artery
- smaller than ulna artery
Relation forearm
- runs under brachioradialis
- runs over biceps / PT / FDS / FPL and PQ
- emerges between BR and FCR at the wrist
- accompanied by venae commitantes
- radial recurrent branch / leash of Henry to BR
Relations wrist
- runs under APL and EPB to dorum of wrist
- over volar aspect of scaphoid
- passes between 2 heads first dorsal interossei and Adductor Pollicis
- branches princeps pollicis and radialis indicis
Relations hand
- anastomoses with deep branch ulna artery
- forms deep carpal arch on the base of the metacarpals
- branches are the volar metacarpal arteries
Larger branch
Relations elbow
- passes deep to two heads pronator teres
- median nerve passes superficial to it and the ulna head PT
Relations forearm
- lies on FDP between FDS and FCU
- runs with 2 venae comitantes
- emerges on radial side of the FCU with the ulna nerve medial to the artery
- posterior interosseous artery: passes dorsally between oblique ligament and interosseous membrane
- anterior interosseous artery: runs on interosseous membrance before passing dorsally proximally to PQ
Relations wrist
- passes into Guyon's canal on transverse carpal ligament
- roof is volar carpal ligament / pisiform medial
- becomes the superficial volar arch
Superficial volar arch
- runs at distal end transverse carpal ligament
- deep to palmar aponeurosis / superficial to FDS tendons
- 3 common volar arteries which each divide into two common digital arteries
Ultimate goal of blood management is to AVOID allogenic blood transfusion
Increased infection rate
- demonstrated in THR
- decreased killer T cells
Increased risk disease transmission
Increased risk transfusion reaction
Increased post-op fever and antibiotic requirements
Increased cost
Increased hospital stay
American Society of Anaesthetists
1. Hb < 6gm/dL
2. Hb > 6 if
- cardiorespiratory disease
- artherosclerotic disease (heart / kidney / legs)
- condition requiring higher oxygen carrying capacity
- symptoms attributed to anaemia
1. Whole Blood
- single donation or Unit
- citrate as anticoagulant (binds Ca which is required by the clotting pathway)
- stored < 5/52 at 4°C
2. Packed Red Cells
- 2/3 of plasma removed
- volume 300ml
- haematocrit = 70% (double that of blood)
- can removed WCC if wish (decrease antigen load)
- Hb rise of 1g/dL / Unit
3. Fresh Frozen Plasma / FFP
- platelets removed
- frozen to preserve labile coagulation factors
- should be ABO compatible
Indications
- massive transfusion
- coagulopathy / DIC
- warfarin reversal
4. Cryoprecipitate
- prepared from FFP by slow thawing at 5°C
- contains F VIII / Fibrinogen / VWF
- usual dose is 10-30 U
Indications
- VWD
- CRF
- Advanced Liver Disease
5. Factor VIII Concentrate
Freeze-dried powder
- pooled product -> high risk disease transmission
- recombinate product
Indications
- gold Standard Haemophilia A
- preferred in VWD
6. Factor IX Concentrate
Prothrombin complex concentrate
- contains IX, X & II
- also high disease risk
Indication
- haemophilia B
7. Platelets
Harvested from fresh blood
- may be pooled or unpooled
- store at room temperature for 5/7
- ABO & Rh specific
Indication
- platelet count < 20 000/mm3 with bleeding
- 1 unit of platelets raises the platelet count of a 70 kg patient by about 7,500x109 / litre
METABOLIC |
INFECTIVE |
TRANSFUSION REACTION |
Hypothermia |
Viral – HIV. B. C. |
Non Haemolytic |
Hyperkalaemia |
Bacterial |
Haemolytic |
Hypocalcaemia |
Fungal |
|
Pumonary oedema |
Prion CJD |
|
Coags/DIC/ARDS |
|
|
Most common
- 2% to 5% of all transfusions
A. Febrile reactions
Most common
- result from the recipient's antibody response to leukocyte Ag in the donor blood
Symptoms
- chills, fever, headache, myalgia, nausea, and, occasionally, severe rigors
Treatment
- supportive
- rarely requires cessation of the transfusion
Leukocyte-removal filters
- diminish the likelihood of febrile reactions
- use of such filters is expensive and retards blood flow
- should be reserved for those patients who have had at least two adverse reactions
B. Allergic reactions
Most are mild, consisting only of slight urticaria
Laryngeal oedema and bronchospasm (anaphylaxis)
- much less frequent
- occurring in less than 1% of such reactions
Treatment is supportive
- subsides spontaneously within several hours of the transfusion
- if multiple severe allergic reactions to transfusions are at high risk of developing further reactions
- ameliorated by using washed components
Risk range from 1:4,000 to 1:25,000
Death
- 1: 100 000
Almost always from mislabelling
- ABO incompatibility
- destruction of the donor RBC
A. Acute
Clinical features
- chills, fever, chest pain, and flank pain
- nausea, hemoglobinuria, shock, a sense of impending death
- tachycardic and hypotensive
Consequences may be fatal
- effects of intravascular hemolysis on the renal and coagulation systems
Management
- immediately stop the transfusion
- return the unused blood and a sample of the patient's own blood to the blood bank for re-crossmatching
Check
- haemoglobin concentration
- platelet count
- partial thromboplastin time
- serum fibrinogen level
- serum potassium levels
Treatment Hyperkalemia
- diagnose on ECG (depressed ST segment, inverted T waves, U wave)
- hydration with generous administration of fluids and diuretics
- monitor urinary output - maintain out put at 75–100 ml/hour
- IV lasix may be necessary to maintain adequate renal perfusion
- consider transferring the patient to an ICU
B. Delayed
Less dramatic
Initial survival of transfused erythrocytes, followed by hemolysis within 1 to 7 days
Continued occult blood loss from a traumatic or surgical source
- rule out delayed hemolytic transfusion reaction as a possibility
A. Circulatory overload
B. Coagulopathy
Dilution of platelets and coagulation factors
- no platelet function at 2/7 in packed cells
- F VIII at 30% after 5/7
- F V at 50% after 14/7
Need to give FFP and Platelets with massive transfusion
- > 1 whole blood volume
- > 6 Units Packed Cells
C. DIC
D. Metabolic disturbances
Hypocalcaemia
- excess citrate forms complexes with serum citrate
Hyperkalaemia
Citrate toxicity
- metabolic alkalosis
- acidosis
E. Hypothermia
- warm bags of blood in massive transfusion
F. TRALI
Transfusion related acute lung injury
- respiratory distress seen after 1 / 2000 transfusions
- development within 6 hours
- may progress to ARDS - like picture
Mechanism
- caused by anti - granulocyte antibodies
- react to donor granulocytes in plasma
Higher incidence in pregnancy
- may be best to use plasma only from men in this situation
A. Bacterial
- rare
- 1 : 500 000 RBC (Yersinia, Serratia)
- 1 : 50 000 platelets (Staph, E coli)
B. HIV
- risk 1 in 2 million
C. Hep B
- risk 1 in 250 000
D. Hep C
- risk 1 in 2 million
1. Minimise intraoperative blood loss
2. Cell saver
3. Reinfusion drain
4. Haemodilution
5. Antifibrinolytics
6. EPO
7. Allogenic blood transfusion
Surgeon
- careful operative exposure through avascular tissue planes
- good hemostasis using an electrocautery and ligatures
- short operating time
- judicious use of collagen pads
- sterile bone wax
- tourniquets
- use of topical agents
e.g. thrombin packs, thrombin powder, Gelfoam, adrenaline soaked gauze, fibrin glue
Hypotensive Anaesthesia
A series of 24 Jehovah's Witness patients had a 30% reduction in intraoperative blood loss with the use of hypotensive anaesthesia
- combined use of narcotic and inhalant anaesthesia
- epidural / spinal
- positioning the patient to reduce engorgement of blood vessels
Method
- lost blood is collected by aspiration or drainage
- filtered / Washed / Centrifuged
- transfused back to patient
Advantage
- intra-op salvage can return up to 60% of lost red blood cells
- good in spine / acetabular fracture / revision hip
- any surgery where large quantities of blood loss expected
Disadvantage
- expensive equipment
- need technical expertise to run
- may not be cost effective
Complications
- cell hemolysis
- air embolism
Contraindication
- malignancy
- sepsis
Results
Elawad Acta Orthop Scand 1991
- RCT of cell saver in THR
- 75% reduction in allogenic blood transfusion
Principle
- blood collected in closed system drain
- filtered but unwashed
- re-infused within 4 - 6 hours
Results
Cheng et al J Orthop Surg 2005
- RCT of reinfusion drain
- significantly reduced allogenic blood transfusion rates
Technique
- pre-operative or intraoperative venesection of 1-2 units
- blood volume replaced by crystalloid or colloid
- post-op reinfusion
Advantage
- intra-operative blood loss is diluted
Contra-indications
- hypovolaemia
- anaemia
- cardiovascular disease
Options
- Aprotinin / E-aminocaproic acid / Tranexemic acid
Results
Wong et al JBJS Am 2010
- RCT of topical application of tranexemic acid
- injected into the TKR at end of procedure
- reduced postoperative bleeding by 25%
Natural erythropoietin
Secretory glycoprotein of 165 amino acids
- secreted by the kidney
- in response to hypoxemia and hemorrhagic stress
- binds to receptors in the bone marrow
- stimulating the production of red blood cells
Advantage
Pre-operative EPO shown to
- increase hemoglobin
- facilitate pre-op autologous blood
- markedly decreased allogenic blood needs
Disadvantages
Expensive
- approximately $500 for each half point of Hb raised
Results
Krackow et al Orthopedics 2002
- EPO in total joint patients
- 3 doses pre-operatively
- matched to control group of patients
- Hb average 1 point higher
- transfusion rate halved
Technique
- multiple serial autologous donations may be obtained
- donor's hemoglobin level must be at least 11 g/dl
Contra-indications
- pre-existing medical conditions
- advanced age
- low pre-op Haematocrit or Hb
- poor erythropoetic response to phlebotomy
Problems
- 60% inadequate erythropoetic response post phlebotomy
- patients who donate blood pre-op are more likely to need transfusion earlier and more frequently
- high cost
- logistical obstacles of storage, collection and transfusion
- high number of bags never used approx 50%
Doctor must act with a proper duty of care
Must act in patient's best interests
Really an informed consent issue
Patient confused with shock
- crying out that he is a JW and doesn’t want blood
- doctor can override if he feels patient not in sound state of mind
- unless patient or family has an advanced health directive
Adult patient fully mentally alert
- doesn’t want blood
- can’t give blood
Child presents needing blood to survive
- parents refuse saying child is JW
- doctor can override if he feels that child not old enough to fully appreciate consequences
Unconscious patient with bracelet saying JW and no blood
- doctor may override if condition life threatening
- only advanced health directive which is carried on person stating refusal for blood will be accepted
Bone healing requires 3 things
- osteoconduction - scaffold / matrix
- osteoinduction - growth factors
- osteogenesis - cells to produce osteoid
Definition
- property of a matrix that supports the attachment of bone forming cells for subsequent bone formation
Substances
1. Autograft
2. Allograft
3. Calcium phosphate
Definition
- process that supports the mitogenesis of undifferentiated mesenchymal cells
- osteoprogenitor cells to become osteoblasts
Substances
1. Autograft
2. BMP
- part of transforming growth factor (TGF) familty
- at least 15 types
- stimulate differentiation of mesenchymal cells
Definition
- generation of bone from bone forming cells
- require presence of osteogenetic cells / osteoblasts
Substances
1. Autograft
2. Autologous bone marrow
Cancellous
- iliac crest
- proximal tibia
- distal radius
- PSIS
Structural
- iliac crest
- fibular / vascularised graft
Properties
- osteoconduction
- osteoinductive
- osteogenic
Properties
- osteogenesis
- osteoinductive factors
Results
Hernigou et al JBJS Am 2005
- injected 20 mls into non infected NU site
- union in 53 of 60
- positive correlation of volume of mineralised callous and concentration of colony forming units
Options
A. Fresh
- inadequate time for disease screening
- HIV / HCV / HBV testing mandatory on donors
B. Frozen
- stored at -60o
C. Freeze-drying
- destroys all osteogenic cells
- limited osteoinductive properties
D. Irradiated
- for sterility
- gamma irradiation (affects mechanical properties)
- ethylene oxide (affects osteoinductive properties)
Properties
Osteoconductive
Types
Cortical strut grafts
- used in periprosthetic THR fractures
- creeping substitution via intra-membranous bone formation
Cancellous allograft chips
- osteochondral ossification
Disadvantages
Osteointegration is invariably
- incomplete
- much slower than autograft
Results
Gibson et al Spine 2002
- RCT of fresh frozen morcellised allograft v autograft in PLF
- comparable results
Concept
Produced by acid extraction of allograft
- retention of collagen and growth factors
- no structural strength
- osteoinductive
- comes as putty or gel
- used in spinal surgery
Results
Lindsay et al Orthopedics 2006
- compared DMB + BM aspirate to autograft in long bone fractures
- comparable findings in regards to union
Vaccaro et al Orthopedics 2007
- prospective study of DMB v autograft in posterolateral spinal fusion
- comparable findings
Properties
- osteoconductive
- provide scaffold
- allow host osteogenic cells to create bone under the influence of host osteoinductive factors
Structure
Ceramics
- highly crystalline structures
- obtained by sintering (heating > 1000o)
- pore size and porosity important
- osteoid formation requires minimum pore size of 100 microns (preferably 300 – 500)
A. Tricalcium phosphate / Chronos
- formed by treating coral with ammonium
- similar structure and porosity to cancellous bone
B. Synthetic hydroxyapatite / Pro Osteon
- may have some osteoinduction properties
- slower in vivo resorption than tricalcium phosphate
- higher brittleness
C. Cements/ Norian
Indications
Metaphyseal defects
- calcaneum
- tibial plateau
- distal radius
Resorption
80% at 10 weeks
- can continue for as long as 30 weeks
- dissolution + osteoclast resorption
Results
Russell et al JBJS Am 2008
- RCT of autograft v calcium phosphate cement in tibial plateau fractures
- significantly reduced rates of subsidence
Buckley et al J Trauma 2009
- RCT of autograft v calcium phosphate past in displaced IA calcaneal fractures
- significantly reduced rate of articular depression
Plaster of paris
- calcium sulfate + water
- forms dihydrate known as gypsum
Properties
- ? osteconductive
- may resorb too rapidly
- takes 4 – 12 weeks depending on size of defect
- low mechanical strength
Indications
- bone graft extender
Types
- MIG
- Osteoset
Results
Niu Spine 2009
- RCT of autograft + BMA v calcium sulphate + BMA in PLF
- significantly reduced rates of union in calcium sulphate group
Background
Group of growth factors / cytokines
- 20 different types
- a type of transforming growth factor
- interact with receptors on the cell surface
Production
- initially extracted from demineralised bone graft by Urist in 1965
- demonstrated ability to stimulate bone growth in rabbits
- now produced by recombinant technologies
Types
Infuse (BMP-2)
OP1 (BMP-7)
Usually delivered on a collagen matrix
Uses
Spinal fusion
Non union long bones
Tibial Results
Friedlaender et al JBJS Am 2001
- As efficacious as autograft in established tibial non union
Govender et al JBJS Am 2002
- RCT of control v BMP in open tibial fractures
– less secondary interventions, accelerated time to union, reduced infection rates
Jones et al JBJS Am 2006
- RCT allograft + BMP2 v autograft in tibial diaphyseal cortical defects
- similar rates of healing, reduced blood loss in BMP group
Spine Results
Vaccaro et al Spine 2008
- RCT OP1 v autograft in PLF spine
- as least as efficious as autograft
Dimar et al Spine 2006
- RCT of iliac crest autograft v rhBMP2 on a collagen matrix
- reduced surgical time, bleeding and increased fusion rates with BMP
Inflammation
- hematoma due to blood vessel disruption
- neutrophils / macrophages / fibroblasts
- remove dead bone
Soft Callus
- collagen formation
- new blood vessels
- osteoblasts and chondroblasts
Hard Callus
- osteoid deposition and mineralisation
- woven bone
Remodelling
- osteoblasts and osteoclasts
- conversion to lamellar bone
Chronic Regional Pain Syndrome
CRPS 1
Sympathetically mediated pain syndrome
- excessive or exaggerated response of extremity to injury, surgery or disease
Manifested by
- intense or unduly prolonged pain
- vasomotor disturbances
- trophic changes
- delayed functional recovery
CRPS 2
Following injury to nerve plexus or peripheral nerve
RSD (regional sympathetic dystrophy)
Sudeck's Atrophy 1900
- acute atrophy of bone associated CRPS
- associated with marked spotty osteoporosis
Usually preceded by trivial injury or surgery
Colles fracture
- most common
- 25 %
- associated with tight cast
Crush injury
Association with coronary artery disease
- like frozen shoulder
Shoulder-Hand Syndrome
- 10% cord or head injury
- i.e more common in stroke patients
- sustain injury to shoulder resulting in CRPS1 in ipsilateral hand
Basis is excessive sympathetic efferent activity
- disturbance of centrally mediated autonomic regulation
Exact pathophysiology is unknown
- may involve all motor, sensory, sympathetic and parasympathetic fibres
- pathological changes are thought to occur in the spinal cord
- abnormal connections form between motor / sensory / autonomic pathways
Injury
- often trivial
- some personalities predisposed
- anxious & hypersensitive
1. Feedback Theory
- abnormal state of activity in interneurones
- continous stimulation of sympathetic & motor efferents
2. Gate Control Theory
- disorder of inhibitory fine tuning
- cells in dorsal horn that modulate afferent transmission
3. Peripheral Cross Stimulation Theory
- peripheral Nerve trauma leads to formation of synapse between sensory afferent & motor efferents
- allows for direct cross stimulation & cycle formation
Upper limb more common than lower limb
Cardinal features
- burning pain out of proportion to injury
- swelling
- stiffness
- vasomotor discoloration
- autonomic = oedema, vascular, sudomotor
- sensory allodynia / pain from non noxious stimuli to skin
Stage 1: Acute 0-3/12
1. Continued localised pain
2. Sensory allodynia
3. Motor - decreased ROM
4. Autonomic - wet with excess sweating
5. Skin changes - Swollen & warm
Xray - normal
Bone scan - positive
Stage II: Dystrophic 3-6/12
1. Proximal spread of pain
2. Skin changes
- cool & dry
- mottled & dusky
- atrophic / shiny skin / decreased hair
3. Oedema of limb
Xray - early osteoporosis on XR
Stage III: Atrophic > 6/12
1. Intractable pain
2. Atrophy of skin, muscles & bone
3. Flexion contractures
4. Diffuse osteoporosis on Xray
Mean duration of symptoms 32 months
Zollinger et al Lancet 1990
- RCT of vitamin C 500mg v placebo post wrist fracture
- significant reduction in prevalence of CRPS 1
Best results with early diagnosis and action
1. Early active ROM / aggressive splinting
- avoid contractures
- passive and active ROM
2. Oedema control
- pressure dressings / garments
3. Desensitisation
- temperature / sensation
- cold water / hot water
- vibrations
NSAIDS
Amitriptyline
Gabapentin
van de Vusse e al BMC Neurol 2004
- RCT of gabapentin v placebo
- 2 three week treatments separated by 2 weeks
- some pain and sensory improvement
- not significant overall
Ketamine
Sigtermans et al Pain 2009
- RCT intravenous ketamine v placebo
- good pain relief
- minimal functional improvement
Regional Sympathetic Blockade
- diagnoses and treatment
- almost always effective
- if not effective consider another cause
- effect usually temporary
- multiple procedures usually required
- if > 4 required, consider surgical sympathectomy
Options
- stellate ganglion blocks
- IV blocks / guanethidine / reserpine
- surgical sympathectomy
Technique
- 0.25% Marcaine
- can use Botox to lengthen the treatment effect
- anterior paratracheal approach
- at C6 level ~ cricoid cartilage
Results
Ackerman et al South Med J 2006
- stellate ganglion blocks with LA
- 40% success if symptoms < 6 weeks
- 36% success if duration 12 weeks
- 25% in group with symptoms averaging 35 weeks
Options
Guanethedine
- false transmitter
- taken up by sympathetic nerve endings
- displaces Noradrenaline
Reserpine
- depletes sympathetic nerve ending stores of Noradrenaline
- decreases storage vesicle reuptake
Results
Paraskevis et al Clin Rheumatol 2006
- bier blocks of guanethedine and lidocaine
- multiple treatments required
- complete pain relief and return to function in all 17 patients
Indication
- good but temporary relief from 4 blocks
Contra-indicated
- poor results with stump RSD
Accumulation of calcium salts in the soft tissues
- Dystrophic or Metastatic
Different from bone formation
- calcification is typically amorphous calcium crystals
- ossification has bone organic matrix (Osteoid) & cells
Dystrophic
Metastatic
Normal serum calcium deposited in damaged tissues
Two phases
Initiation
- exact mechanism uncertain
- necrosis exposes denatured proteins
- binding PO4 exposed
- act as nucleation sites for precipitation of calcium
Propagation
- accentuated by hypercalcaemia
Pathology
Deposits amorphous & non-crystalline
Many forms
- pyrophosphates
- carbonates
- oxalates
- Fe salts
Hydroxyapatite crystals may form
- May progress to Ossification
Degenerative tissues
- atherosclerosis
- damaged heart valves
- infected lymph nodes
- degenerating tumours
- chondrocalcinosis
- CPPD deposition in cartilage
Occur in normal tissue whenever there is hypercalcaemia
- may occur widely
- blood vessels / kidney / lungs / gastric mucosa
HyperCalcaemia
- Primary hyperparathyroidism
- Tertiary hyperparathyroidism / CRF
- malignancy
- immobilisation
- vitamin D Intoxication
- Milk Alkali Syndrome
- Sarcoidosis
Exact mechanism unknown
-? 2° local high pH
- deposition of basic calcium salts
Calcification
- central pattern
- often increased opacity compared with bone
Ossification
- peripheral pattern
- similar density to bone
Calcification
- calcium salts only
Ossification
- osteoid matrix
The deposition of calcium in joints
- often in degenerative cartilage
- many different causes
Crystals can be salts of
- Calcium pyrophosphate dihydrate (CPPD)
- Dicalcium phosphate hydrate
- Calcium hydroxyapatite
- Calcium oxalate
WHIP A DOG
Wilson's
Haemochromatosis, hyperparathyroidism
Hypophosphatasia
Idiopathic
Pseudogout, pernicious anaemia
Amyloid, acromegaly
Diabetes
Ochronosis
Gout
Calcium in articular cartilage
- fine linear densities
- parallel to subchondral bone
Hemangioma (commonest)
AV Malformation
Synovial sarcoma
Chondrosarcoma
MO / HO
Eptheloid sarcoma
TB calcified LN
Pathological bone formation in soft tissues
In elbow
- 3% of trauma
- 89% if head injury + trauma
Completely different
1. Myosisitis Ossificans Circumscripta
- post traumatic
- more common
- recognised as a consequence of neurological injury
2. Myositis (Fibrodysplasia) Ossificans Progressiva
- rare inherited condition
- progressive fibrosis of muscles, ligaments and tendons that is ultimately fatal
1. Traumatic
Most common
- deltoid
- quadriceps
- elbow joint
2. Non-traumatic
Adductor tendon in horse riders
Unclear
Progression beyond normal healing to 0ssification
Typically single major traumatic incident
- direct blow to muscle
- joint dislocation ± fracture
Can occur with repeated minor trauma
- adductor Longus in horse riders
2° muscle inflammation & repair process abnormal
- extensive cellular infiltration
- collagen laid down
- collagen undergoes dystrophic calcification
- chondroblasts differentiate into osteoblasts
- osteoid produced
History of trauma
Initial pain / swelling / warmth
Develop hard mass
- slow resolution of pain
Changes occur 2-4 / 52 after injury
Initial cotton candy appearance
- then osseous in appearance
- not attached to bone
- can be resorbed
Mature bone peripherally
Osteosarcoma
STS
Hemangioma
MO
- diaphyseal (OS metaphyseal)
- intact cortex (OS fractures)
- mature bone peripheral with central fibrous tissue (OS mature centrally)
- pain and swelling improves with time (OS worsens)
- normal osteoblast on biopsy
High risk
- i.e. sports player with trauma to thigh / large haematoma
Minimise haemorrhage & inflammation
- ice & elevation
- active ROM / avoid passive ROM
- 3/52 course of NSAIDS
Indication
- large mass of bone
- significant pain, stiffness & weakness
Timing
- delayed > 12/12 (usually delay minimum 18 months)
- early resection = Recurrence
- don't resect until neurological recovery complete (i.e. if head injury)
Maturity
- local pain and tenderness resolved
- mature trabecular pattern on xray
- no progression on xray
- alkaline phos normal
- cold bone scan
Prognosis
- poor with in patient with incomplete neurological recovery and spasticity
Widespread ossification of connective tissue
AD
Spine
Major joints of upper limb
Poorly formed bone
Dense scar tissue
Islands of poorly formed cartilage
Patients have short 1st metatarsal / metacarpal
Die of restrictive lung disease
Unknown
Rare
Black population
1st or 2nd decade
Painless firm swellings over joints
- very common at large joints
- hip and shoulder
Cosmetic & functional problem
- may ulcerate & discharge
Calcium levels normal
Serum phosphate usually high
Complete surgical excision
- recurrence common
> 10 mg / dl
- must be corrected for albumin
Malignancy
- multiple myeloma / lung cancer / breast cancer
Hyperparathyroidism
- elevated PTH
High mortality associated with hypercalcaemia of malignancy
40% albumin bound
50% ionised and active
Lethargy / confusion
- most commonly seen in malignancy
Kidney stones / abdominal pain / depression
- more likely seen in hyperparathyroidism
Forced diuresis
- fluids + frusemide / loop diuretic
Bisphosphonates
- IV dose
Calcitonin
- gives rapid but short lived reduction
- need to be coadministered with other medications
Dialysis
- required if kidneys unable to cope with fluid diuresis / renal failure
Fall in level promotes tetanus
Chvostek sign
- tapping masseter muscle induces spasm
Trousseau Sign
- flexion of thumb & wrist with extension of fingers
Carpopedal Spasm
Prolonged QT interval on ECG
1. Vit D Deficiency
- lack sunlight
- dietry lack
- malabsorption
- liver / renal disease
- anticonvulsants
2. Hypoparathryoidism
- throidectomy
- infiltrative (carcinoma, haemachromatosis)
- idiopathic
3. Hypothroidism
4. Hypophosphataemia (Vit D resistant Rickets)
5. Hypomagnesemia
Source
- ingested in diet
- absorbed in small intestine / duodenum
- under control of vitamin D
Excretion
- through kidney
- majority is reabsorbed
- under control of vitamin D
Storage
- 99% stored in bone
Source
- produced by parathyroid glands
- in response to hypocalcaemia
Action
1. Vitamin D
- stimulates activation of Vit D in kidney
- vit D then increases absorption / decreases excretion / increases release from bone
2. Bone
- stimulates release of calcium from bone by indirect inhibition osteoclasts
3. Kidney
- increases resorption of calcium
- increases excretion of phosphate
Generation of Vit D
Vitamin D3 ingested and absorbed
- activated by sunlight
- need 10 - 15 minutes 3 x per week
25 hydroxylated in liver
1 alpha-hydroxylase in kidney
- active 1,25 vit D3
- calcitriol
- this is under PTH control
Action Vit D
1. Intestine
- increases Ca and PO4 absorption
2. Kidney
- decreases Ca and PO4 excretion
3. Bone
- increases Ca and PO4 release
A framework of medical education for essential physician competencies
- aimed to improve patient care
- 7 essential roles
Medical Expert (Central Role)
Communicator
Collaborator
Professional
Manager
Scholar
Health Advocate
Communicator
- able to obtain and pass along information in verbal and written manner
Collaborator
- ability to work effectively within the team
Professional
- committed to patients, profession and society
- act with integrity, honesty and ethics
- acountable
Manager
- organising teams, delegating and managing resources
Scholar
- committed to obtaining, interpreting, providing and disseminating medical knowledge
Health Advocate
- promote health of individual, community and population
Medical Expert
To produce sufficient thrombin to rapidly convert soluble fibrinogen into insoluble mass of fibrin
Coagulation cascade must be localised & limited to site of tissue injury
1. Immediate Control of Blood Loss
Vascular Phase
- damage to blood vessel triggers reflex vasoconstriction
Platelet phase
- damage blood vessels release serotonin and adrenalin
- stimulates vasoconstriction and platelet aggregation
- platelets release thromboxane A2
- stimulates further platelet formation
- platelets form plug
2. Clot Formation
Formation of fibrin
- red cells & platelets bound together by strands of fibrin
- final common pathway is Factor X activation
- factor X converts Prothrombin to Thrombin
- thrombin converts Fibrinogen to Fibrin
Intrinsic System
- started by activation of factor XII
- secondary to exposed subendothelium
- HMWK & PreKallikrein-->Kallikrein
- ends with activation factor X
Extrinsic System
- tissue Thromboplastins
- released by tissue damage
- activate factor VII
- activates factor X
3. Removal of Clots
Fibrinolytic enzymes remove clot as vessel wall repaired e.g plasmin
Function
- when subendothelial structures are exposed to flowing blood, platelets adhere to subendothelial VWF & collagen
- platelets then release granules
- ADP & Thromboxane A2
- potentiates aggregation & stimulates vasoconstriction
Bleeding time
BP cuff inflated to 40 mm Hg & incision made
- time until bleeding ceases is noted
- normal < 9 minutes
Prolonged with
- platelet count < 50,000/mm
- platelet function impaired (NSAIDs, aspirin)
- von Willebrand Disease
Prostacyclin
- produced in vessel walls
- has antithrombotic effect
- high intimal concentration discourages luminal obstruction by platelets
- antagonist effect to TXA2
Antithrombin III
- circulating protease
- binds & inhibits Thrombin
- inhibits II, IXa, Xa, XIa, XIIa
- ↑ APTT (Intrinsic)
- heparin globally increases its activity
- LMWH only works against Xa
Protein C & S
- Vit K dependent
- natural anti - Thrombolytics
- activated by Thrombin
- familial lack rare ++ 1: 16 000
- decreased amount associated with spontaneous DVT
Tissue Plasminogen Activator
- converts plasminogen to plasmin
- plasmin degrades fibrin
- e.g. streptokinase, urokinase, TPA
Hereditary bleeding disorder due to defective and/or deficient factor VIII molecule
Inherited X-linked recessive disorder
- occurs almost solely in males
- female carriers usually asymptomatic
- 30% have no family history
FVIII deficiency
X-linked disorder
- 1:10 000
- all ethnic groups
- all parts of the world
Reduction in circulating levels of functional FVIII
- decreased amount or defective FVIII
- carriers have 50% of normal levels
- bleeding problem if <5%
FVIII complex protein with 2 forms
- small molecule with coagulant activity (VIII:C)
- larger molecule which circulates with von Willebrand factor (VIII:vWF)
FIX deficiency
Also X linked recessive
- less common
- 1:30 000
Similar spectrum of disease
- identical to haemophilia clinically
- treat with Factor IX cryoprecipitate
Intrinsic pathway
Factor VIII
- an essential cofactor for factor IXa
- catalyses conversion of factor X => Xa
- in the presence of activated factor VIII the rate of factor Xa production is dramatically increased
Without factor VIII activity
- delayed clot formation
- excessive bleeding and poor wound healing
1. Haematomas
2. Haemarthrosis
3. Bone cysts and pseudotumours
<1%
- frequent spontaneous bleeding in early life (haemarthroses)
<5%
- severe bleeding following injury
>5%
- milder disease post-traumatic bleeding only
Most frequent cause of death is AIDS (transmitted in 1980s)
Haemorrhage into subcutaneous connective tissue or into muscle
- with or without trauma
- superficial or deep
Problems
- expand locally to compress organs, vessels, nerves
- expand distally to retro-peritoneal / retro-pharyngeal
- may cause compartment syndromes
Can lead to muscle contractures / atrophy & nerve palsies
- volkmann forearm contractures
- iliopsoas haematoma and femoral nerve palsy
- recurrent calf bleeds and equinus
Acute
- rapid tense swollen red tender articulation
- painful and stiff
- fever and leukocytosis
- symptoms decrease quickly
Subacute
- after 2 or more haemarthroses
- complete recovery of joint not evident
- peri-articular swelling secondary to boggy synovium
- joint motion is restricted
- contractures evident
- muscle atrophy
Chronic
- after subacute present for 6-12 months
- severe and persistent contractures
- final stage fibrotic contracted and destroyed articulation
3 types
1. Simple cyst
- confined within fascial envelope of muscle
2. Cyst in soft tissues
- interferes with blood supply of adjacent bone and periosteum
- resorption of bone and cyst formation
3. Result of sub-periosteal bleeding
- resultant stripping limited by aponeurotic or tendinous attachments
As cyst increases
- compresses and destroys muscles, nerve and bone
- likely to reform unless completely removed
- tend to become multi-loculated
- erodes through tissues into viscera and skin
- predisposed to infection
- difficult to differentiate from malignant tumours
- needle biopsy with caution
Differential Diagnosis
- primary and secondary neoplasms
- infection
AVN
- epiphyseal fragmentation and collapse
- especially hip and ankle
- secondary to intra-osseous bleeding or intracapsular bleeding
- causes increased intra-articular pressure, vascular occlusion and subsequent osteonecrosis
Ectopic Ossification
- occurs in peri-articular tissues
Fractures
- fracture healing normal
- pseudotumours may develop at site of fracture
Chondrocalcinosis
- haemosiderin alters articular mechanics that leads to cartilage calcification
- blackish fluid containing clots within recesses of articular cavity
- embedded within synovial membrane or adherent to capsule
- with each bleed resorption less
Synovium
- discolouration of synovial membrane secondary to haemosiderin absorption
- hypertrophy, hyperplasia and increased vascularity
- synovial villi more numerous
- synovial tissue and adjacent capsule/soft tissues undergoes fibrous proliferation
- appears similar to inflammatory pannus
Cartilage
- becomes discoloured
- reveals focal areas of fibrillation, erosion, necrosis
- may expose sub-chondral bone
- modified in several ways
- loss of subchondral bone plate (therefore calcified cartilage rests on cancellous bone)
- trabecular thinning and resorption (enlarged marrow spaces which appear cystic)
- granulation tissue extends from bone into overlying cartilage
Sub-chondral cysts
- represent sites of intra-osseous haemorrhage
- cysts common beneath sites of abnormal cartilage
Periosteal bleeding (pseudo-tumours)
- can lead to secondary periosteal bone formation
- creates irregular and expanding bony contours
Immature skeleton
- chronic hyperaemia of epiphyseal cartilage
- leads to accelerated maturation and enlargement of epiphyses
Platelet count / Bleeding time normal
APTT increased
PT Normal
Low factor VIII: C Activity
Think Haemophilia if destroyed joint & epiphyseal overgrowth + lytic bony lesion
Affects hinge joints
1. Knee
Widened femoral condyles and intercondylar notch
- distal condylar surface may appear flattened
- squaring of the inferior pole of patella
- subluxation patella and particularly postero-lateral tibia on femur
NB
- not specific for haemophilia
- many of changes similar to those seen in juvenile chronic arthritis
2. Elbow
3. Ankle
Stage I
- soft tissue swelling + effusion
- periarticular osteoporosis
Stage II
- overgrowth / widening of epiphysis
- surface irregularity / small erosions
- joint space maintained
Stage III
- some narrowing of joint space
- extensive bony erosions
- sub-chondral cysts
Stage IV
- cartilage destruction
Trauma
Juvenile onset RA
PVNS
Infection
Other coagulation disorder
Patients treated after 1985 can expect to have normal life spans
- older patients had high incidence of AIDS
- now recombinant
Replacement of missing / defective component
Factor VIII concentrate
- initially pooled / high risk of HIV
- then heat treated to eliminate this risk
- now produced by recombinant technology
FVIII
- has a half life of 12 hours
- 1 u/kg increases VIII by 2%
- given tds
Aim
- 15% for mild bleed
- 30% for severe bleed ~ 1000u tds
- give ASAP at home
Problem
- 10% will develop antibodies
- IgG inhibitor
- use FVII in life threatening emergency
Other options
- FFP: concentrations of FVIII too dilute
- DDAVP produces a rise in FVIII proportional to initial level
Usually managed at home
- IV F VIII 1000U tds if 70kg
- analgesia (Not NSAID)
- splint & compression first 24 hours
- once bleeding stops ice packs & mobilise
Place of washout controversial
- reduces pain & swelling
- no evidence that it decreases risk of arthropathy
Treatment
1. Prednisone 5 days
- 2-3 doses FVIII for level > 30%
- physiotherapy
2. Prednisone 6 weeks
- FVIII > 20% 3 x week
- physiotherapy
- synovectomy
- contractures
- OA hip / knee / elbow / ankle
F VIII
Levels
- 100% pre and post op
- > 60% for 2/52
- 30% for 6/52
Haematologist
- close working relationship with surgeon
- adequate reserves of concentrate available in advance
- lab available to perform unlimited assays for the factor
- identify antibody/inhibitor production
- screen for HIV / HBV / HCV
FVIII inhibitor
Increasing problem
- new techniques involving FEIBA
- factor eight inhibitor bypassing activity
Lauroua et al Haemophilia 2009
- FEIBA in 12 patients having major and minor operations
- successful bleeding control
Operative technique
As many procedures at one sitting as the patient can take
- monitor factor VIII intra-operatively
- pneumatic tourniquets
- tight careful wound closure to avoid dead space
- avoidance of diathermy (coagulated areas slough after surgery)
- wound suction to deep wounds minimum 24 hours
- no aspirin platelet inhibitors post operatively
- no intramuscular injections
Post-operatively
- Need F VIII for MUA and ROS
Indication
Chronic synovitis
- stage 1 or 2
- reduces incidence of bleeding & improves function
- slows progression of disease but doesn't prevent
Results
Rodriguez-Merchan Int Orthop
- 27 surgical synovectomies of the knee
- average age 13
- better results in arthroscopic than open
- reduces incidence of hemarthrosis and improve ROM
- effects diminish with time
- disease progresses, but likely more slowly
Patti et al Arthroscopy 1996
- arthroscopic synovectomy in 9 ankles
- reducing bleeding incidence and improved ROM and function
1. Fixed ankle equinus
- T Achilles equinus
2. FFD and valgus knee
- supracondylar osteotomy
AKJ / STJ
Results
- good functional results
- good long term survival
- higher rates of infection
Rodriguez-Merchan JBJS Br 2007
- 35 TKR followed up for average 7.5 years
- average patient age 31
- 97% survival at 7.5%
- 94% good or excellent results
- 1 deep infection requiring 2 stage revision
- 1 patient required embolisation
Silva et al JBJS Am 2005
- 90 TKR in hemophilia
- rate of infection was 16%
- 12 required removal, 9 for late infection
- knee society scores good or excellent in 97%
Kelley et al JBJS Am 2005
- 34 patients average age 38 followed up for 8 years
- 3 late deep infections
- 21% rate of aseptic loosening
Chapman-Sheath et al JBJS Br
- TER in 7 elbows
- one deep infection
- excellent functional results at 4 year follow up
Obstructive disease
- decreased absorption Vitamin K as it is fat soluble
- Vit K dependent factors affected
- II, VII, IX & X
- raised INR
Hepatocellular Disease
- impairs synthesis of all coagulation proteins
- bleeding episodes treated with FFP or Cryoprecipitate
Occurs with impaired intake or malabsorption
- Inflammatory Bowel Disease
- blood contains no functional forms of II, VII, IX & X
- reversed in 1/7 of Vit K administration
Phospholipid antibodies
- Broad family of autoantibodies that target phospholipids
- can be either procoagulant or anticoagulant
Lupus anticoagulant antibodies
- procoagulant
- associated with thromboembolic events rather than clinical bleeding
Antiphospholipid syndrome
Need 1 clinical and 1 laboratory for diagnosis
Clinical
- Vascular thrombosis
- Catastrophic antiphospholipid syndrome
- Complications of pregnancy (spontaneous abortions / premature intra-uterine deaths)
Laboratory
- detected on 2 tests 6 weeks apart
- anticardiolipin antibodies
- lupus anticoagulant antibodies
Prevalence
Antiphospholipid antibodies is 1-5% in young adults
SLE : anticardiolipin & lupus anticoagulant – 15-30%
Investigation
All patients with a first thrombotic episode should be screened for anticardiolipin & lupus anticoagulant antibodies
Treatment
Antiphospholipid antibodies
- no thrombosis
- modify 2° risk factors if have antibodies
- aspirin is not protective against thrombosis
Antiphospholipid syndrome
- warfarin 2-2.9 decreases thrombosis rate
Definition
Platelet count < 50,000 x 10.6/L
Causes
1. Defective production
- disturbane of bone marrow
- i.e. secondary to medication
2. Excessive destruction
Drug-Induced Thrombocytopaenia
- Quinine, Sulphonamides, Digoxin, Morphine & H2 antagonists
- drug binds to platelets & acts as Hapten
- form antigenic substances
- complement activation and Platelets lysis
HITS
- 2° AB- heparin-platelet complexes formed & cause platelet aggregation
- thrombocytopaenia from thrombosis
- rapidly reversed once heparin ceased
- should monitor platelet count in patients on heparin
Idiopathic Thrombocytopenic Purpura
- relatively common disorder
3. Excessive splenic pooling
4. Massive transfusion
Effects
Spontaneous bleeding if < 20,000
Post-traumatic bleed increased if < 100,000
Most common of the bleeding disorders
- 1:100
vWF
- needed for platelet adhesion and platelet-platelet interactions
- also carrier for factor VIII / protects it from rapid breakdown
Gene on chromosome 12
1. Reduced production VWF
2. Increased proteolysis VWF
Leads to diminished platelet adherence at sites of vascular injury
Type I
- quantitative deficit
- mild reduction in VIII:vWF / AD
Type II
- qualitative deficit
- reduction in proportion of HMW multimers / AD
- mild clinical features, bleeding post-surgery, epistaxis
Type III
- barely detectable FVIII:vWF (= VIII:C) / AR
- clinically resembles Haemophilia A
Bleeding times
- prolonged with normal platelet count
APTT
- slightly increased
vWF assay
- Ag based test
VIII:C
- decreased levels
Positive FHx
Common history
- easy bruising
- bleeding post circumcision
- menorragia / post partum bleeding
- nose bleeds, gum bleeding
- bleeding post dental extraction
Severe hemarthrosis
- type III
Desmopressin / DDAVP
- stimulates release of vWF from endothelial cells
- useful only in type 1 / quantitative deficit
Cryoprecipitate
- 1 bag / 10 kg bd
- several days after major operation
Informed consent
- involves the patient actively participating in the management process with respect to
- goals of management
- therapeutic alternatives
- potential benefits
- risk of complications
Risks / Benefit / Outcomes / Alternatives
Must be in layperson terms
Must be able to comprehend discussion
X-ray & major investigation findings
Diagnosis & why that conclusion has been reached
NHx of condition
Management options including non-operative
Recommended treatment
Prognosis with and without surgery
Nature of surgery
Risks of surgery
Next step if proposed treatment not effective
Questions answered
1. Advanced Health Directive
2. Relative or friend
3. Legal Guardian
No specific age limit
- need to be mentally competent
- i.e. 14 - 16 is old enough to sign own consent
Mini Mental State Exam
Heterogeneous group of diseases characterised by
- hyperuricaemia
- recurrent attacks of acute arthritis
Diagnosis confirmed by
- crystals of Monosodium Urate in synovial fluid
- tophi ("Porous stone") urate in soft tissues
- renal urate stones
Adult men
- M:F = 20:1
- peak 40-60 years
Part of metabolic syndrome
- obese / HTN / high cholesterol / diabetes
Often have positive FHx
Prerequisite is hyperuricaemia at some stage
- determined by balance between production & excretion
Production
- breakdown of nucleic acids
- oxidation of Purine bases (Guanine & Adenine)
- converted Inosine > Hypoxanthine > Xanthine > Uric Acid
Excretion
- 2/3 excreted into urine
- 1/3 into GIT
- uric acid filtered at glomerulus
- reabsorbed in PCT
- secreted in subsequent PCT
Primary
Disturbance of Purine biosynthesis secondary to heritable error of metabolism
- usually idiopathic
- some specific enzyme known eg Lesch-Nyhan syndrome
Lesch-Nyhan Syndrome
- rare
- X-linked recessive
- absence of enzyme in purine pathway HGPRT
- leads to excessive uric acid formation & gout
- young boys with mental retardation and self-mutilation
Secondary
Diet high in purines
- alcohol / meat / seafood
Myeloproliferative disease
- leukaemia
Chronic hemolysis
Chemotherapy
Drugs eg salicylates, thiazide diuretics
Starvation, ketoacidosis
Alcoholism
Secondary abnormal renal excretion of Uric acid
- diuretics
- CRF
Acute Gouty Arthritis
Sustained hyperuricaemia
Develop monosodium urate deposits
- in synovial lining cells & in cartilage on PG which are inert
- subsequently released into synovial fluid & CT
- precipitates at > 8 mg/dl (trauma, low pH)
Sufficient number of crystals in joint precipitates acute inflammation
- phagocytosis of crystals
- release of chemotactic factors & inflammatory mediators
- activate complement & platelets
- disrupt lysosomes in leucocytes with cell rupture
Chronic Gouty Arthritis
Tophi of Monosodium Urate Monohydrate Crystal aggregates
- deposited in synovium, cartilage & tendon sheaths
- lead to cartilage destruction & periarticular cyst formation
4 stages
1. Initial asymptomatic hyperuricaemia
2. First attack of acute gouty arthritis
3. When this settles, hyperuricaemia persists
- recurrent attacks
- frequency of attacks varies, may increase
4. Chronic gout
- joints no longer recovering from acute attacks
- arthritis & tophi develop
Hyperuricaemia
- in men begins at puberty
- in women starts at menopause
Risk of gout increases with
- serum urate level
- duration of hyperuricaemia
- usually develops after 20-30 years
Only 5% of hyperuricaemic patients develop gout
Takes days / weeks to resolve
- pain-free intervals of variable length
Acute Gouty Arthritis
Predominantly affects distal lower limb
- 70% initially attack 1st MTPJ (Podagra)
May also involve
- Other joints in foot
- ankle
- knee
- hands
Usually monoarticular, rapid onset
- excruciating night pain
- hot red shiny swollen joint
- very painful to touch
- may have systemic features
- fever / leucocytosis / raised ESR
Onset may be spontaneous
May be precipitated by
- trauma
- excessive activity
- diet excess
- alcohol consumption
- diuretics
- systemic illness
- surgery
Chronic Gouty Arthritis
Arthritis
- after repeated attacks of gout
- asymmetric destructive arthropathy
- often involves small joints in hand
Tophi
- 20% of cases
- white mass of sodium urate crystals
- visible underlying thinned-out skin
- may necrose overlying skin
Sites
- periarticular subcutaneous tissue
- helix of ear
- tendon sheaths especially Achilles
- olecranon / prepatellar bursae
Renal Stones
- 15% of cases
- radiotranslucent uric acid stones
Serum Uric Acid
Attacks of gout occur when levels of serum uric acid change
- not necessary to have increased serum urate during acute attack
- elevated serum urate in patient with painful joint not diagnostic of gout
Synovial fluid
Specimen must be anticoagulated
- must be very careful with sample as any water or alcohol put into it will dissolve the crystals
Monosodium urate crystals
- diagnostic if found in synovial fluid
- needle-shaped crystals 10um long
- lying free or in neutrophils
Test
- negatively birefringent under polarised light & parallel to 1st order red compensator
- bright yellow when parallel to compensator
Synovial fluid analysis
- WCC of 1000 to 70 000 x 10.6/ L
- predominantly neutrophils (< 70%)
Note
- presence of crystals doesn't exclude infection
- infection precipitates urate
24 hr Urinary Uric Acid Secretion
> 1100mg /day
- 50% chance renal stones
- treat with Allopurinol
Chronic Gouty Arthritis
- usually in feet in phalangeal heads
- characteristic periarticular bony defects
- punched out lytic appearance
- overhanging sclerotic margin (Martell's sign)
- also joint space narrowing & secondary OA
- no osteopenia compared with RA
Pseudo-gout
Septic arthritis
Acute bursitis
Cellulitis
RA
OA
Seronegative spondyloarthropathy
Colchicine
Action is as anti-inflammatory
- inhibits activation of inflammatory mediators by crystals
- very effective
- rapid response strongly suggestive of diagnosis
- 1 mg then 0.5 mg q2h up to maximum 6 mg / day
- continue till patient improves / diarrhea occurs / maximum dose
- 80% of patients unable to tolerate optimum dose because of GIT side-effects
NSAID
Usually better tolerated than colchicine
- indomethacin most commonly used
- 50 mg t.d.s
- side effects include GIT toxicity / Sodium retention / CNS disturbance
ACTH
Adrenocorticotrophic Hormone
- good for acute attack
- minimal side effects
- single 40 IU IM injection
Glucocorticoids
Oral Prednisone
- if colchicine not tolerated / NSAID contraindicated
Intra-articular steroids
- may be used for severe monoarticular attack
- especially knee
Initial
Lose weight
Increase fluids intack
Aim to decrease Purine intake and avoid precipitating factors
- alcohol
- diuretics
- diet - meat, seafood
2nd Stage
- Probenecid
3rd Stage
- Allopurinol
- beware hypersensitivity / bone marrow suppression
Absolute indications
- CRF secondary to kidney stones
Relative indications
- > 3 acute attacks / year
- polyarticular gout
- tophi
- uric acid > 500 mmol/l
Options
1. Increase Renal Uric Acid Excretion / Uricosuric
- Probenecid
- require good renal function
2. Decrease Uric Acid Synthesis
- Allopurinol
Allopurinol
Inhibits Xanthine Oxidase
- 300 mg/day (150 if CRF)
- hypersensitivity side effects in 20%
Causes decrease in serum uric acid & this may precipitate acute attack of gout
- initiation of treatment should be accompanied by Colchicine or NSAIDS
- never used in acute gouty attack
- can shrink tophi if keep serum urate < 0.4mmol/l
Side effects can be fatal
- rash
- alopecia
- marrow suppression
- hepatitis
Dystrophic or Metastatic
1. Metastatic
- hypercalcaemia / hyperphosphatemia
2. Dystrophic
- more common
- onto damaged connective tissue
- tendon / ligament / cartilage
- calcific tendonitis shoulder
- Pellegrini-Steida lesion MCL
Deposited around chondrocytes & into avascular portion of CT
- crystals grow by accretion
- early on like cream
- later like chalk
- can be inert or surrounded by inflammatory reaction
- crystal shedding into joint causes synovitis
Two syndromes
1. Acute or Subacute Periarthritis
Pain near a large joint
- not intra articular
- after minor trauma
- warm & swollen tendon / ligament
- calcific tendinitis rotator cuff
- Pellegrini-Stieda lesion MCL
2. Chronic Destructive Arthritis
HA crystals found in association chronic erosive arthritis
- unknown if cause or effect
- destructive arthropathy seen in shoulder with cuff arthropathy
- i.e. Milwaukee shoulder
- whether related to HA unknown
Crystals too small to be seen with light microscopy
- hence will not see on aspiration
Periarthritis seen as calcium in tendon
- especially rotator cuff
- chronic HA arthritis doesn't show on xray as well as CPPD
Periarthritis
- RICE
- NSAID
- HCLA
Surgical removal
- calcific tendonitis
- problematic Pellegrini Steida
Chronic Arthritis
- treat as OA
- early arthroplasty if rapid bone destruction
Degenerative arthropathy due to Alkaptonuria
Rare hereditary disorder of tyrosine and phenylalanine breakdown
Homogentisic acid enzyme deficiency
- accumulate Homogentisic Acid
- product of tyrosine breakdown
Homogentisic acid deposited in cartilage & other soft tissues
- polymerises
- pathology probably due to a disruption of collagen cross links by metabolites of homogentisic acid
Urine turns dark on standing
- also when alkalised
- hence the name
Sweat stains clothes
Cartilage & connective tissue stained grey
- brownish-black pigment in connective tissue
- calcified cartilage
- deposits in virtually all cartilages
- discs, sclera, skin
Arthropathy
- early OA secondary to brittleness
- presents 4th decade
- back pain then knees / shoulders / hips
- most common presenting complaint
Spondylosis
- especially affects spine
- difficult to differentiate from ankylosing spondylitis
- dense calcification of discs with narrowing of intervertebral space
Pseudogout
- Calcium Pyrophosphate Dihydrate (CPPD) crystals
- inflammatory arthritis of older individuals
Chondrocalcinosis
- refers to any calcium in cartilage / menisci
M:F 2:1
Patient > 50
Sometimes familial
DM
Hypothyroidism
Gout
Hyperparathyroidism
Haemochromatosis
Pernicious Anaemia
Onchronosis
CPPD deposited in
- joint capsule
- articular cartilage
- fibrocartilage / meniscus
Crystals seen at margin of degenerating cartilage
- pyrophosphate generated at chondrocyte surface in abnormal cartilage
- combine with calcium to form crystals
Occasionally the crystals are released into the joint & an acute arthritis results
- activation of vasoactive & chemotactic factors
- neutrophils attracted & phagocytose crystals
- release of lysosomal enzymes into joint fluid
Chronic chondrocalcinosis predisposes to development of 2° OA
- crystals embedded in articular cartilage have desiccating effect
1. Asymptomatic Chondrocalcinosis
Majority of people
- incidental finding
- calcium of menisci
- usually involved with degenerative changes
2. Pseudogout
Rapid onset inflammatory arthritis
- peak in 24/24
- subsides in 1/52
May be provoked by
- trauma
- surgery
- illness
Usually affects large joints
- Knee > Shoulder > Wrist
- typically monoarticular
- less pain than gout
3. Chronic CPPD Arthropathy
OA 2° CPPD
Pseudo-Osteoarthritis
- polyarticular disease like OA
- in hips & knees
- due to CPPD in cartilage altering the biomechanics
In more unusual joints for OA
- ankles, shoulders, elbows
- very common in PFJ
- has radiodense crystals
4. Pseudo- Rheumatoid Arthritis
Acute synovitis & chronic arthritis
- rapidly progressive joint destruction
CPPD crystals seen extracellular & in neutrophils
- rhomboidal
- weakly positively birefringent
- IE Blue parallel to 1° order red filter & 135° to polarizer
Chondrocalcinosis
Calcium in fibrocartilage & CT
- punctate densities
- menisci / TFCC / pubis / annulus
Findings of OA usually present
Unusally joints
- PFJ
Ca / PTH
U&E
Serum Fe / Fe studies
TFT
Serum Alk Phos
Hyperparathyroidism
X-rays show subperiosteal erosions
Blood tests show hypercalcemia / increased PTH
Ochronosis
Often severely affects spine / shoulders / hips / knees
Hemochromatosis
Disorder where iron deposited in many tissues including articular cartilage
- concomitantly get cirrhosis of the liver / CCF /diabetes / bronze skin
- chondrocalcinosis often prominent feature
- calcification of multiple joints and discs
- serum Fe and IBC raised
1. NSAIDS
2. HCLA
3. Colchicine
- 80% response
4. Joint washout
Don't debride / perform synovectomy
Worsens symptoms
Disseminated Intravascular Coagulation
Results from excessive activation of either extrinsic or intrinsic coagulation pathway
- multiple small clots
- consumptive coagulopathy
1. Excessive Extrinsic Activation
Secondary to extensive cellular destruction
- thromboplastins +++ released into circulation
- these tissue factors activate VII
Sepsis with disruption of phagocytes common cause
- numerous other causes
2. Excessive Activation of Intrinsic Pathway
Less common
- extensive endothelial damage
Cancer: lung / pancreas / prostate
Obstetric: abruption / pre-eclampsia / amniotic fluid embolism
Severe trauma and burns
Gram negative sepsis
Bleeding or thromboembolism
Bleeding
- more common secondary to thrombocytopaenia or coagulation factor depletion
- surgical sites
- skin / IV lines / venupuncture
- respiratory / urological / GIT
Increased PT / APTT
Increased
- FDP / fibrin degradation products
Decreased
- fibrinogen
- platelets
Control of underlying disorder
FFP / Cryoprecipitate
Rarely a problem
- may get CVA or coronary artery thrombosis
- anticoagulate with Heparin
Virchow's Triad
1. Venous stasis
2. Hypercoagulability
3. Endothelial damage
Starts as platelet nidus at valves
- thrombogenic materials elaborated by platelets
- leads to development of fibrin thrombus
- thrombus grows
Thrombus may
- detach as embolus
- be completely dissolved / recanalise
- organise with valve incompetence
1. Patient
Previous DVT
Increasing Age
Obesity
Varicose veins
Immobility
Pregnancy
OCP / HRT
Smokers
Inherited Thrombophilia
Paralysis
Malignancy
Recent MI
2. Disease / Surgery
Trauma or surgery
Malignancy
Infection
High Risk
Family history
Past History DVT/PE
OCP / Pregnancy / HRT
OT to pelvis & hip
Obesity
Hypercoagulable state
Varicose veins
Moderate Risk
Major surgery in age > 40
Major medical illness
Any large surgical procedure
Obese
Low Risk
Minor surgery < 30 min
Immediate mobilization
DVT rates without prophylaxis
- THR 50-70%
- TKR 50%
PE rates without prophylaxis
- asymptomatic PE 10 - 20%
- symptomatic PE 2%
- fatal PE 0.1 - 0.2%
DVT
- peak Day 3
- 80% of DVT occur during inpatient stay
- can occur as late as day 40
PE
- 50% fatal PE's > 3/52 i.e. occur at home
Calf DVT
- calf DVT has 20% chance of propagation
- ? PE less likely
Proximal thrombi
- are at greatest risk of embolism
- 50% chance PE
Issue
- should all high risk patients get regular ultrasound?
- i.e early diagnosis and treatment to avoid PE
Problem
- 80% PE without clinical evidence DVT
- 2/3 patients with fatal PE die in 30min
PE leads to hypoxaemia from
- VQ mismatch
- Right Heart Failure
1. Clinical
- inaccurate
- non specific & non sensitive
- 50% patients with DVT have no clinical signs
- 50% with suggestive clinical signs have negative venogram
2. Venography
Gold standard
- sensitivity & specificity >95%
- outlines entire deep venous system of leg
Disadvantage
- invasive
- expensive
- 5% can't cannulate foot
- requires expertise
- risk of inducing DVT 1%
- contrast reaction 0.02%
- doesn't visualise pelvic veins
3. Duplex Ultrasound Scanning
Real-time US combined with colour imaging
- veins visualised
- femoral & popliteal veins visualised
- presence of lumen, compressibility & flow assessed
- sensitivity & specificity for proximal thrombi 95%+
- sensitivity only 70% calf DVT
Advantage
- non-invasive
- rapid & inexpensive
- use only above the knee
Disadvantage
- poor test if poor equipment & inexperienced user
Results
Schellong et al J Thromb Haemost 2007
- VENUS study
- compared venography to compression ultrasound in same patient
- 1100 orthopedic patients on oral anticoagulant
- venography rate of DVT was 19%
- ultrasound rate of DVT was 11.5%
- US sensitivity 31% specificity 98%
Clinical
- unhelpful
- symptoms & signs non-specific
D Dimer
- always raised post op
- useful in low risk patient
- negative D dimer in this group excludes DVT
ECG
- usually sinus tachycardia
- right heart strain - S1 Q3 T3 (20%)
CXR
- usually normal
- exclude pneumonia
ABG's
- sensitive but not specific
- hypoxemia / hypocapnia / respiratory alkalosis
VQ Scan
Te99 labelled Albumin spheres trapped in capillaries / Xenon33 Gas in alveoli
- both detected by scintiscan
- compared with each other for mismatch
Advantage
- non-invasive
Disadvantage
- results not always clear-cut
- intermediate and high risk
- require further investigation
- low probability - 2% risk PE
CT Pulmonary Angiogram
Advantage
- definitive
Disadvantage
- difficult & expensive
- risk of contrast reactions
MRI
Useful for pelvic DVT
- patient with entire leg swollen
- negative ultrasound
- particularly post THR / pelvic / acetabular surgery
Established DVT & PE
- treat with anticoagulation
- prevent further clot propagation / embolisation
- allows fibrinolytic system to act unopposed
- does not directly dissolve thrombus
Calf DVT
- treatment debatable
- risk PE low but not zero
- 20% propagation rate
- usually treat for 3 months
- can give aspirin and repeat US in 7 - 10 days
Screening for Thrombophilia
Protein C / Protein S deficiency
Anti-thrombin 3 deficiency
Factor 5 Liaden (activated protein C / APC)
Lupus anticoagulant
Cardiolipin
Can be divided into
- mechanical prophylaxis & chemoprophylaxis
- preoperative, intraoperative, & postoperative
Mechanical
Early mobilisation
TEDS
Sequential Compression Devices
Foot pumps
Chemoprophylaxis
LMWH / Heparin / Warfarin / Aspirin / Oral Factor X inhibitors
Screen for high-risk groups
- obesity
- Family Hx
- previous DVT/ PE
- varicose veins
- yypercoagulable states
- OCP / HRT / smoking
Stop smoking & HRT
Preoperative clinic to encourage exercises & post-op regimen (education)
- admit day of surgery
Keep well-hydrated
Regional anaesthesia
Planes et al JBJS Br 1991
- RCT of GA v Spinal with enoxeparin in patients with THR
- 6% proximal DCT in each group
- 0% distal DCT in GA group v 5% rate distal DVT in spinal group
- enoxeparin 40 mg sc day before GA
Intraoperative mechanical prophylaxis
- compression on other leg
Consider
Tourniquet
- cuff width at least 30% diameter of leg
- tapered low-pressure cuff if possible
- minimal tourniquet time
Minimal tissue damage & bleeding
- activates coagulation cascade
Avoid extremes of flexion for long periods
Avoid extrinsic pressure to limb
- care of position & extrinsic pressure to other leg
1. Early mobilisation
2. Early chemoprophylaxis
3. Early mechanical prophylaxis
- TEDS
- foot-pumps & Sequential Compression Devices
- applied in OT
- until mobile
Check calves daily for tenderness & swelling
FDA
- does not approve chemoprophylaxis for any spinal procedure
Epidural haematoma
- most often on removal of epidural
- 1:2 000 without chemoprophyaxis
- 3: 1 000 with Clexane
- not within 24 hours of insertion or removal
Biochemistry
Naturally occurring anticoagulant
- mixture of sulphated mucopolysaccharide chains
- heterogenous molecular weights
- average ~ 15 000 daltons
Found in granules of mast cells
- mast cells have IgE receptors on surface
- discharge when IgE-coated antigens bind to receptors
- mediate allergic reactions
Action
Facilitates action of Anti-Thrombin III
- binds to it & causes conformational change
- increased affinity for thrombin (x 1000) & Xa
- also inhibits aggregation of platelets
Pharmacology
Calcium / Sodium heparin
Half-life
- 2 hours
Reversed with Protamine
Treatment Dose
Bolus 5000 units IV
Maintenance 1000 u /hr
Maintain APTT 70-120
Levels
- check after 6 hours
- 6 hours after any change in infusion rate
- daily APTT otherwise
Prophylaxis Dose
Fixed low-dose heparin
- 5000 units s/c bd or tds
Complications
Wound haematoma
Heparin Induced Thrombocytopenias / HITS
- paradoxical thrombosis
- occurs in 10-15% of patients receiving heparin
- due to drug-antibody binding to platelets
- resolves promptly with ceasing heparin
- 80% cross-reactivity with LMWHs
Definition
Fractionated heparin
- derived from heparin by chemical / enzymatic depolymerisation
- MW 5000
Action
Pure Anti Xa
- to inactivate thrombin the chain has to attach to antithrombin III & heparin simultaneously
- because LMWH are too short to do this they only inhibit Xa
- less platelet interaction
Increased anti-thrombosis
Decreased bleeding
- because no anti-thrombin action
Pharmacology
Longer T1/2 x4
Increased bioavailability 90% vs 30%
- doesn't bind to plasma proteins as heparin does
Clexane / Enoxeparin
Derived from the intestinal mucosa of pigs
Dosing
- 0.5 mg/kg od for prophylaxis
- 1mg/kg od therapeutic dose
No monitoring required
Reduce dose
- GFR < 30
Reversal
- protamine has some, but reduced effect
Fragmin / Dalteparin
Dose
- 5000IU od
Results
Hull et al Arch Int Med 2000
- RCT of 1000 THR of warfarin v dalteparin
- warfarin had rates total DVT 24%, proximal DVT 1% and symptomatic DVT 4.5%
- dalteparin had rates total DVT 13%, proximal DVT 1% and symptomatic DVT 1.5%
- dalteparin preoperatively had slightly decreased rates of total DVT but increased bleeding
Mechanism
Act directly on Factor X
- do not use ATIII as an intermediate
Advantage
Oral administration
- make OPD dosing more simple
- don't require monitoring
Interaction
Statins
Xarelto / Rivaroxaban
Dose
- 10 mg od
Kakkar et al Lancet 2008
- RCT of 2500 THR patients
- 35 days of rivaroxaban v 14 days enoxeparin
- incidence DVT and non fatal PE 2% in rivaroxaban v 9% in enoxeparin (significant)
- incidence of bleeding was 6% rivaroxaban and 5% enoxeparin (non significant)
Turpie et al Lancet 2009
- RCT of 3100 TKR patients
- rivaroxaban v enoxeparin 10 - 14 days
- incidence of DCT / non fatal PE 7% rivaroxaban v 10% enozeparin (significant)
- incidence of bleeding 0.7% rivaroxaban v 0.3% enoxeparin (non significant)
Mechanism
Structural analogue of vitamin K
- blocks the activation of vitamin K
- factors II, VII, IX, X & Protein C + S are vitamin K dependent
Disadvantage
1. Paradoxical procoagulant effect
- initial period
- needs cover with another anticoagulant
2. Teratogenic
- contraindicated in pregnancy
3. Delayed Effect
- half-life of factors ranges between 6 and 60 hours
- FVII has the shortest half-life and is the first to be affected
- decrease of FVII increases PT
- there is a window period of 3/7 with increased PT but no true anticoagulation exists
- must cover patient for the first 3 days
4. Requires monitoring
Metabolism
Oral warfarin is readily absorbed & almost entirely albumin-bound
Metabolised in liver
Potentiators
- Cimetidine
- Phenytoin
- Trimethoprim
- Cephalosporins
- Tramadol
Inhibitors
- Rifampicin
- Phenobarbitone
Reversed with parenteral Vit K or FFP
Dosing
Starts simultaneously
- 5 mg nocte for 2 days
- then daily dose as per INR
- usually 3 - 5 mg
Treatment INR
- 1.5-2.5 DVT
- 2.5-4.0 PE
Prophylaxis INR
- 1.5 - 2
Results
Mismetti et al J Thromb Hemost 2004
- meta-analysis
- vitamin K antagonists less effective than LMWH in preventing total or proximal DVT
- no significant difference in rates of major bleeding or haematoma
Mechanism
- irreversibly inhibits cyclo-oxygenase in platelets & megakaryocytes
- blocks thromboxane A2 formation
Dosing
150 - 300 mg od
Disadvantages
GI bleeding
Results
PEP Trial
- RCT aspirin v placebo after 13 000 hip fractures and 4000 TKR/THR
- > 99% follow up for 35 days
Indications
- complications of anticoagulation therapy
- recurrence of PE whist fully anticoagulation
- high rate of death if subsequent event / further embolic load on right ventricle
Disadvantage
Surgical procedure
- inserted through groin
- need to be removed
Results
Bicalo et al J Arthroplasty
- filter vs IV heparin
- 3 of 28 complications for heparin
- 1 of 26 for filter
Early Mobilisation +
Compression Stockings
Pneumatic Compression Devices
Foot Pumps
Mechanism
Antiembolism stockings
- apply graded compression
- highest at ankle
- lowest above knee
- attempt to increase flow
- may cause venous stasis if improperly fitted or roll down
Precaution
Check pulses
- not to be used if vascular compromise
- ABI < 1.0
Size correctly
Results
Sachdeva et al Cochrane Database Review 2010
- 8 x RCT's of GCS alone v no GCS
- rates DVT 13% v 26%
- 10 x RCT's of GCS + another method v other method alone
- rates DVT 4% v 16%
Results
Kakkos et al Cochrane Database Review 2008
- RCT of PCD alone v PCD + another method
- PCD alone had incidence symptomatic PE 3% and DVT 4%
- PCD + another method incidence symptomatic PE 1% and DVT 1%
- pharmacological alone had DVT 4% v pharmacological + PCD DVT 1%
Disadvantage
Not tolerated by some patients
- uncomfortable
- disturbs sleep
Results
Warwick et al JBJS Am 1998
- RCT of enoxeparin v foot pumps
- DVT rate of 13% enoxeparin and 18% foot pumps
- no major proximal DVT in either group
Host
Wound
Operating room environment
Antibiotics
Operative technique
Post operative
Immunocompromised
RA (0.9 v 2.2%)
Psoriasis
DM (6%)
Poor nutrition
Obesity
UTI
Prednisone
Previous operation
Previous infection
Age
Prolonged pre-op hospitalisation (Admit DOS)
Active concurrent infection (Oral cavity / UTI / chest)
Shave and prep immediately prior to surgery
Preparation
- alcoholic chlorhexidine best
Drapes
- plastic adhesive +/- impregnated
Breaches in skin (local / distant)
- cover
- delay elective surgery if able
Old scars
- incorporate if able
Wound irrigation +/- antiseptic
Limit Number of personnel / Amount of traffic
Airflow / laminar flow
Helmet / aspirator suit
Gown (goretex, polyproylene)
Hoods and masks
Ultra- clean air
UV light
MRC Trial Lidwell OM, Br Med J 1982
Multicentre study of sepsis after 8000 TKR / THR
- randomised
3 Groups
- conventional theatre clothing
- total joint replacements in a ultra-clean air OT, conventional theatre clothing
- total joint replacements in a ultra-clean air OT, body exhaust suits or utilising plastic patient isolators
Findings
- ultraclean air 1/2 joint infections conventional ventilation
- whole body exhaust suits + ultraclean air 1/4 infection rate
Pre-operative
- at time of induction
- repeat if operation goes 2+ hours
Antibiotics in cement
- if joint replacement
Post-operative
- little evidence
- many continue for 24 hours
Prep by gowned assistant
Avoid glove perforations
- double glove & change regularly
Avoid prolonged use of suction tip
Avoid splash bowl for washing instruments
Meticulous technique
- gentle handling, avoid devitilising tissue, don't undermine skin, careful closure and suturing
Minimise operating time
Avoid haematoma
- close deep space
- ? use drain
Avoid pressure on wound
Avoid distant pressure areas
Avoid haematomas
Debride / washout expanding haematomas
Superficial skin necrosis / formal debridement
Serous wound drainage (persistent = formal debridement)
Avoid bacteraemia
Minimise IVC, IDC
Skin can't be sterilised
Purpose
- remove transient & pathological bugs
- reduce resident flora to low level
- antiseptic agents effectively eliminate bacterial count at the operative site
- recolonization begins within 30 minutes from hair follicles
Chlorhexidine
Iodine
Povidine - Iodine
Alcohol
Action
- disrupts cell membranes
- bactericidal & virucidal
- gram positive > gram negative
Advantage
- good residual effect as binds to protein in Stratum Corneum
- less inactivation by organic material than iodine
- occasional allergy
Disadvantage
- slow onset of effect
- cationic molecule which is incompatible with soaps & other anionic materials
- poor against spores & fungus
Types
Skin Preparation
- 0.5% Chlorhexidine Gluconate in 70% alcohol
Surgical Scrub
- 5% Chlorhexidine Gluconate ç lathering agent
Advantage
- effective against gram positiv / negative / viruses / funguses
- sporicidal after prolonged contact
Disadvantage
- poor residual activity
- high incidence of skin sensitivity reactions
- toxic to osteoblasts, fibroblasts & keratinocytes
- inactivated by organic material
- an anion so incompatible with cations / chlorhexidine
Skin preparation
Weak Iodine - 2.5% I in 70% alcohol
Tincture - 2.5% I + 2.5% K+ I-
Structure
- Iodine +
- Povidine (Polyvinyl-Pyrrol-Idone)
Advantage
- bactercidal & fungicidal
- gram positive > gram negative
- slowly sporicidal
- introduced to decrease irritative effect
- decreased skin sensitivity reactions
Skin preparation - Betadine
10% aqueous solution
10% in 30% or 70% alcohol
Scrub 7.5% Povidine Iodine with Soaps
Advantage
- bactericidal, fungicidal, virucidal
- gram positive and negative
- destroys 90% of skin microbes in 2 minutes
- increases the efficacy of other antiseptics when used concomitantly
Disadvantage
- doesn't destroy spores
- activity drops below 50% concentrations
- rapid activity, but not sustained
- inadequate alone
Skin Preparation
Daroulche et al N Eng J Med 2010
- RCT of alcholic chlorhexidine v povidone-iodine
- alcholic chlorhexidine significantly reduced superficial and deep infections
Hand washing
Tanner et al Cochrane Database Review 2008
- alcohol rub at least if not more effective in decreasing CFU's than aqueous scrub
- chlorhexidine aqueous scrub more effective than povidone-iodine aqueous scrubs
|
Chlorhexidine |
Iodine |
Povidine Iodine |
Alcohol |
General |
Cationic
Disrupts cell membrane |
|
Iodine complexed with anionic detergent |
Denatures proteins 90% microbes within 2 min Activity decreases below 50% |
Presentation |
Skin prep - 0.5% chlorhex gluconate with 70% alcohol Aqueous hand scrub - 5% chlorhex gluconate |
2.5% iodine in 70% alcohol |
Skin prep - 10% aqueous - 10% in 30 / 70% alcohol Surgical scrub 7.5% |
|
Efficacy |
Gram pos > gram neg Bactericidal Viricidal
No spores / fungal |
Gram pos = gram neg Bactericidal Viricidal Fungicidal
Sporicidal with prolonged contact |
Gram pos > gram neg Bactericidal Viricidal Fungicidal
Slowly sporicidal |
Gram pos = gram neg Bactericidal Viricidal Fungicidal
no spores |
Clinical |
Skin contact 2 min Residual effect- binds to stratum corneum occ allergy |
Poor residual activity Percutaneous absorption |
Variable residual Min skin absorption Decreased skin sensitivity Decreased irritative effect |
Rapid action
Not sustained De-fat action Desiccates skin |
Decontamination
- removal of gross organic debris
Disinfection
- process of eliminating all microorganisms except bacterial spores
Sterilization
- process to eliminate or destroy all forms of microbial life, including bacterial spores
1. Wet heat
2. Dry heat
3. Chemical
4. Irradiation
Autoclaving
- most reliable
- metal instruments
- glass
- some plastics, fabrics & rubbers
Technique
- 121° >103 kPa ~ 15 minutes
Flash
- 134° 205kPa 3 minutes
Uses
- glassware
- oils & fats
Technique
- fan-driven oven
- 160° C
- minimum 2 hours
indications
- instruments damaged by heat
A. Ethylene Oxide
Uses
- items unable to withstand heat of >60° C
- instruments with electrical, fibre-optic or electronic components
- heat sensitive plastics
Technique
- ethylene oxide must reach all surfaces of article to be effective
- At 60°C in 60% humidity
- minimum time 12 hours
B. Glutaraldehyde
Most common used
- thoroughly cleaned instrument immersed in solution
- sterilisation with immersion for 10 hours
- disinfection with immersion for 20 minutes
- precautions with use & thorough rinsing because very irritant
Hydrogen Peroxide made to release free radical by radiowave - 45° C
Temperature | Pressure | Time | ||||
Wet Heat | Complete | 121o | 103kpa | 15 min | ||
Flash | 134o | 205kpa | 3 min | |||
Dry Heat | 160o | 120 min | ||||
Chemical | Ethylene Oxide | 60o | 12 hours | |||
Gluteraldehyde | 10 hours |
Bacteriocidal
- B Lactams
- Aminoglycosides
- Flouroquinolones
- Fusidic acid / rifampicin
- Co-trimoxazole / Nitroimidazoles
- Vancomycin
Bacteriostatic
- erythromycin / clindamycin
- tetracyclins
- suphonamides / trimethorim / nitrofurantoin
- Chloramphenicol
Bacteriostatic and bacteriocidal are relative terms and also depend on the organism
Cell wall synthesis
- B lactams
- Vancomycin
Protein synthesis
- Aminoglycosides
- Macrolides (erythromycin, clindamycin, azithromycin)
- Tetracyclines
- Chloramphenicol
- Fusidic acid
DNA replication
- Quinolones
DNA synthesis
- Nitroimidazoles
- Nitrofurans
RNA polymerase
- Rifampicin
Folate metabolism
- Trimethoprim
- Sulphonamides
Source
- derived from moulds of Penicillium
Structure
- ß-lactam ring with attached Thiazolidine ring
- drugs vary with relation to attached radicals
MOA
Bacteriocidal
- inhibit bacterial cell wall synthesis
- bind to PBP's (penicillin binding proteins)
- inhibit membane-bound Transpeptidase
- inhibit Peptidoglycan synthesis
- leads to weakening of cell wall & death
Resistance
Beta-lactamase (penicillinase)
- Splits ß-lactam ring of penicillin nucleus
Organisms
- S Aureus
- Some E coli
- Proteus Mirabilis
- Pseudomonas Aeruginosa
Flucloxacillin & Clavulinic Acid
- resistant to penicillinase
- have high affinity for ß lactam
- bind it but are not hydrolysed
Other forms of resistance exhibited by Staphylococci
- Absence of PBPs secondary to mutation
- Failure of drug to activate autolytic enzymes in cell wall
Classification
1. Penicillinase Sensitive
A. Penicillin G / Benzylpenicillin
- Acid-labile
- IV only
B. Penicillin V / Phenoxymethylpenicillin (PVK)
- acid-resistant
- oral
Uses
- S pyogenes / S pneumoniae
- G-ve cocci / N Meningiditis
- G+ve Bacilli / Clostridium
- Treponema Pallidum / Syphilis
2. Penicillinase Resistant
Flucloxacillin
- Oral & parenteral
- Resistance 2° absence PBP
Dicloxacillin
- ? Less Hepatoxicity 1:50 000
Uses
- S. aureus
3. Broad Spectrum
Amoxycillin
- Effective against Gram negative
- Oral & parenteral
Uses
- All of Penicillin-sensitive group plus
- G-ve Bacilli / Haemophilus / Salmonella
Kinetics
Absorption
- Flucloxacillin is fairly well absorbed
- Amoxycillin is well absorbed
- Food decreases absorption
- Give before food
Penetration
- Penetrates most tissues well
- Penetrates CNS very well
Excretion
- in urine
- 90% by tubular excretion
- Can be blocked by Probenocid
- T1/2 30-60 min
Dosage
Benzylpenicillin - 600-1200mg q6h IV
PVK - 500 mg qid oral
Flucloxacillin
- 1-2 g q6h iv
- 500 mg qid
- Kids 25mg/kg/Dose IV q6/24
Adverse Affects
Hypersensitivity
- Occurs in up to 5%
- Antigens are degradation products of penicillin
- Use desensitisation if no other option available
- Desensitisation is dangerous
Anaphylactic shock
- Rare 0.05%
- Fatal in 10%
Skin Rashes
- Common
- broad range
Stevens- Johnson Syndrome
- Usually occurs at 3-10 days
- Ampicillin causes specific maculopapular rash
Interactions
Probenocid
- inhibits renal tubular secretion of penicillin
- enhances effect of Penicillins
Clavulinic Acid
- Clavulinic Acid inhibits bacterial Penicillinase
- Combined with Amoxycillin
Source
- discovered in 1945 in Sardinian sewer
Structure
- ß-lactam
- dihydrothiazine ring fused with four-member beta-lactam ring
MOA
- Bind to enzymes involved in cell wall biosynthesis
- Penicillin-binding proteins (PBP's)
First Generation
Drugs
- Cephalothin / Cephalexin / Cefazolin
Activity
- active against most Gram positives
- limited Gram negative activity
- exception E coli / Klebsiella / Proteus
Second Generation
Drugs
- Cefoxitin (Mefoxin)
Activity
- generally less Gram positive activity
- more effective against Gram negatives
- more active against H Influenzae
Third Generation
Drugs
- Cefotaxime / Ceftriaxone / Ceftazidime
Activity
- even less effective against Gram positives
- more effective against Gram negative organisms
- effective against Gram negative enterics (Klebsiella Proteus Enterobacter Serratia)
- Ceftazidime is effective against Pseudomonas
Pharmacological Properties
Route
- most not orally absorbed (except cephalexin)
Distribution
- variable protein binding (Cephalexin 15% - Ceftriaxone 90%)
- widely distributed (Interstitial & Peritoneal fluids / Urine)
- CSF - 3rd Generation only
- all enter bone
- all have excellent synovial fluid concentrations
Excretion
- via kidney
- active tubular secretion and Glomerular filtration
- accumulate with CRF (T1/2 of Cephalexin increases from 1 hr to 20 hrs)
Adverse Reactions
Hypersensitivity
- anaphylaxis rare
- skin rash 1-5%
- cross sensitivity with Penicillin ~ 5%
- no CI if delayed Penicillin SE i.e. Rash
- avoid with immediate Penicillin SE
GIT
- diarrhoea in 1-10%
- pseudomembranous colitis uncommon
Other
- Cephalothin may potentiate nephrotoxicity of Gentamicin
Indications
S. Aureus Infections
- first generation
- drug of choice in Penicillin allergy
Strep Infections
- first generation
Ceftazidime
- pseudomonas OM
Prophylaxis
First generation are drugs of choice
- effective against common org
- inexpensive
- low toxicity
- achieve high concentration in bone and soft tissue
Cefazolin is drug of choice
- longer T1/2 than Cephalothin
- may achieve better bone levels
Source
- discovered in 1940's
- derived from soil bacteria
MOA
Multifactorial bacteriocidal effect
- bind to Gram negative bacterial cell wall & affect permeability
- bind to bacterial ribosomes & affect protein synthesis
Gentamicin
- attaches to specific receptor protein on bacterial 30s ribosome
- block initiation complex of peptide formation
- results in misreading of mRNA & non functional protein
- ribosome breaks up into fragments
- result is cell death
Resistance
1. Lack of receptor on ribosome
- chromosomal mutation
2. Produce drug destroying enzymes
- plasmid-induced
3. Permeability defect
- plasmid-induced
Pharmacokinetics
Concentration-Dependent killing
- one single bolus dose works better than divided doses in 24 hrs
- concentration-dependent
- dose is 4-5 mg/kg over 60 min
- peak levels not required
- level at 18 hours to check trough
Antimicrobial synergy
Synergy between Aminoglycoside & Penicillin / cephalosporin for Gram positive cocci
Distribution
Administered IV over 30 minutes
- minimal absorption from GIT
- large volume of distribution
- cross membranes poorly / blood brain barrier
- exception is renal tubular & inner ear cells
- enters synovial fluid easily
Metabolism
Not metabolised
- 99% excreted unchanged in kidney
Side Effects
Allergies rare
Kidney damage
- injury to renal PCT
Inner ear damage
- damage to cochlea & vestibular apparatus
- appears to be less with once daily dose
- idiosyncratic & dose related
Indications
Effective against the vast majority of gram negatives
- Aerobic G - Bacillus
- Klebsiella
- Enterobacter
- Serratia
- Pseudomonas (Tobramicin)
Resistance rare
Structure
- Fluoroquinolone
Mechanism
- interfere with bacterial DNA synthesis
- inhibits the A subunit of bacterial topoisomerase
Side Effect
- toxic to paediatric cartilage
Indication
- broad spectrum
- gram negative and positive
- potent oral antipseudomonal
- not as effective against staph as cephalosporins
MOA
- bacteriocidal
- anti cell wall synthesis
- different mechanisms to B Lactams
- inhibits early stage of Peptidoglycan synthesis intracellular
- requires cell wall penetration
Indications
- Pseudomembranous Colitis orally
- MRSA
- prophylaxis if high rates methicillin resistance in community
Kinetics
Absorption
- very poorly GIT absorbed
- very irritant to veins
Excretion
- renally excreted unchanged
- T1/2 8 hrs
Administration
- dilute in 200 ml saline
- administer over 2 hr
Side Effects
Ototoxicity
- dose-related
- don't use with hearing impairment
- Withdraw if tinnitus occurs
Nephrotoxicity
- dose-related
- don't use with renal impairment
- monitor renal function
Hypersensitivity
- "Red man's syndrome"
- due to Histamine release
- from too rapid infusion
Tissue necrosis
- from extravasation
Interactions
Care with other nephrotoxic drugs
- Aminoglycosides
Gram Positive cocci
Staphylococcus epidermis / aureus
- 1/2 - 2/3 all infections
Streptococcus viridans
- 25%
Other
- Enterococci
- Strept. pyogenes / pneumoniae
- Neiserria
Gram positive bacilli (all anaerobes)
Clostridiae (bacilli)
Listerius
Bacillus
Gram negative bacilli
10-20%
Coliforms
- E Coli, Proteus, Salmonella, enterobacter, acinetobacter
Pseudomonas
Hemophilus
Gram Negative Cocci
Neiserria
Gram negative Anaerobes
Bacteroides
Resistant microbes
MRSA, MRSE & VRE
Cytoplasmic Membrane
Innermost layer
- present in both Gram positive and negative
- functions as a permeability barrier and transport system
Cell Wall
Function
- maintains cell shape
- protects high internal osmotic pressure
- cell wall injury = Lysis
Gram positive
- thick Peptidoglycan Layer (x5)
Gram negative
- thin Peptidoglycan Layer
- second outer membrane of lipopolysaccharide (endotoxin)
Capsule & Glycocalyx
Extracellular Polymer
- if forms condensed, well-defined layer, called Capsule
- if forms loose meshwork of fibrils, called Glycocalyx
Slime
- polysaccharide Glycocalyx
- envelopes bugs infecting prosthesis
- S aureus & epidermis
- Pseudomonas
Function
- adhere to and survive on synthetic surfaces
- protects from host-defense factors / Complement fixation / Neutrophil ingestion
- 500 x more resistant
"Window of Opportunity"
- theoretical period when can kill microbe before biofilm forms
- basis behind Acute Early TJR infection regimes
- time frame unknown ? 2/52
Spores
- gram positive rods
- Bacillus & Clostridium
- occurs in unfavourable conditions
- resistant to drying / antiseptic
- only killed by Betadine
- killing of spores is the difference between Sterilization & Disinfection
1. Gram Stain
Difference is in cell wall
- reason unclear
Technique
- flood with Crystal Violet and wash
- flood with Iodine applied and wash
- all microbes are blue at this point
- carefully decolourise with ethanol
- counterstain with safranin
Gram positive
- retain crystal Violet - Iodine complex
- purple
- don't take up counterstain
Gram negative
- cells completely decolourised
- take up safranin
- take on contrasting Red
2. Acid - Fast Stain / Ziehl-Neilsen
- AFB retain Carbol-Fuschin stain even when decolourised with acid-alcohol
- most commonly Mycobacterium
Process
- red Carbol-fuschin applied
- heated on steam bath
- decolourised with hydrochloric acid in alcohol
- contrasting blue counterstain applied
Acid-fast bacteria appear red
- others are blue
Four basic methods of action
1. Cell Wall Synthesis
- ß lactam drugs
- Vancomycin
2. Inhibition of Cell Membrane Permeability
- Polymyxins
- Amphotericin B & Fungi
3. Inhibition of Protein Synthesis
- Gentamicin
- Erythromycin
- Tetracyclines
4. Inhibition of Nucleic Acid Synthesis
- Quinolones (Ciprofloxacin)
- Rifampicin
- Sulfonamides
- Trimethoprim
1. Genetic Exchange
- plasmids
- Entire chromosomes
2. mutation
Mechanisms
- degrade antibiotics / B Lactamases
- modify receptor sites or target
- alter 30s binding site of ribosome
- decrease bacteria's permeability to the antibiotic
- protective glycocalyx
- produce cell membrane antibiotic pumps
Characteristics
- gram positive cocci
- arranged in irregular clusters / grapes
- non motile
- non spore forming
Culture
Grow on most media in aerobic conditions
- S aureus is golden
- S epidermidis is white
Resistance
ß lactamase production
- plasmid mediated
- resistant to some penicillins & cephalosporins
Methicillin Resistance
- independent of ß lactamase production
- mechanism unknown
- function of cell wall structure
Tolerance
- inhibition without death
- due to lack of activation of autolytic enzymes (PBP) in cell wall
Toxins & Enzymes
1. Exotoxin
- A-haemolysin
- ß-haemolysin
- endotoxin C
- haemolytic & pyogenic
2. Enterotoxin
- food poisoning
3. Coagulase
- clots citrated plasma
- produced by S. aureus
- S. epidermidis is coagulase negative
4. Other
- hyaluronidase
- staphylokinase
- exfoliative toxin (Toxic Shock Syndrome)
Pathogenesis
S. aureus
- pathogenic & invasive
S. epidermidis
- found on skin
- rarely suppurative
- may infect prostheses
Pathology
Abscess
- furuncle, carbuncle, pimple
- focal suppuration necrosis
- coagulase coagulates fibrin around lesion to produce wall
- liquefaction of necrosis occurs
Characteristics
- gram positive
- arranged in chains (Strep throat like necklace)
Enzymes
Haemolysins
- haemolyse RBC's
- complete = ß-haemolysis
- incomplete = Alpha-haemolysis
Streptolysis
- Grp A ß-haemolytic Strep produce
- Streptolysin O
- Streptolysin S
Streptokinase
- converts plasma plasminogen to plasmin
- digests fibrin
Hyaluronidase
- splits Hyaluronic acid
- aids in spreading bacteria
Erythrogenic Toxin
- causes rash of scarlet fever
ß-Haemolytic
- Produce Haemolysins
Group A
- S Pyogenes
- majority of pathogens
Cause
- erysipelas
- strep throat
- impetigo
- infective endocarditis
- Rheumatic Fever
- Acute Glomerulonephritis
Group B (B=baby)
- S Agalactinae
- normal flora of female genital tract
- important in neonatal infections
Group G (Remember G=Gut)
- normal enteric flora
- Enterococci / S. faecalis / S. faecium
Alpha-Haemolytic
S Pneumoniae
- Cause pneumonia
S Viridans
- normal respiratory flora
Peptostreptococci
- gut anaerobes
Treatment
All sensitive to Penicillin G
Characteristics
- large heterogenous group
- gram negative rods
- non spore-forming
- facultative aerobes or anaerobes
- natural habitat is GIT
Toxins
1. Endotoxins
Definition
- complex lipopolysaccharides derived from bacterial cell walls
- often released when bacteria lyse
Effects
- act on various cells especially Neutrophils
- cause release of endogenous pyrogens / Acute phase reactants
- stimulate inflammatory response
- activation of complement Cascade with release of vasoactive substances
Activation of coagulation cascade
- hypotension
- early vasoconstriction
- later vasodilatation & increased vascular permeability
- leads to shock / DIC / Metabolic acidosis
2. Enterotoxins
Produce diarrhoea
- E coli (Traveller's diarrhoea)
- Shigella (Dysentery)
- Vibrio Cholerae (Cholera)
Groups
1. Coliforms
- aerobic rods found in GIT
- large & heterogenous group
- all resemble prototype Escherichia coli
- also Klebsiella / Enterobacter / Serratia
- constitute large part of normal aerobic intestinal flora
- become pathogenic when reach tissues outside intestine
- commonest cause of UTI
- various sensitivities
- most sensitive to gentamicin
2. Pseudomonas
- motile aerobic Rods
- widely distributed
- may be found in intestine & skin
- forms blue-green pus & sweetish odour
- common in respiratory tract
- treated with Ceftazidime / Ticarcillin
Also:
- Salmonella
- Shigella
- Vibrio
- Campylobacter
Characteristics
- Gram negative Bacillus
- Non-encapsulated form is part of normal respiratory flora
- Encapsulated form produces suppurative respiratory infection
Pathology
May enter bloodstream in small children
- meningitis
- septic arthritis
Infants < 3/12 have Maternal Ig
- by 3 years, most children have antibodies
- 3/12 - 3 years risk period
- immunization now available
- HIB has decreased ++++
Treatment
Many susceptible to Amoxicillin
- some produce ß lactamase
Cefotaxime
Characteristics
Gram Diplococcus
- Neisseria Meningitidis / Meningococcus
Pathology
Enter via nasopharynx
- travel via blood stream
Bacteraemia produces
- high fever
- haemorrhagic rash
Clnically
Meningitis
Waterhouse-Friderichsen Syndrome
Sepsis & DIC
Circulatory collapse
Neisseria Gonorrhoeae / Gonococcus
Characteristics
- attach to surface epithelial cells
- attack mucous membranes of Genitourinary Tract / Rectum / Eye / throat
- produces suppuration
Clinically
- urethritis in males
- PID in females
- septic arthritis & OM (secondary to bacteraemia)
- arthritis in knees, ankles & wrists
Treatment
Most serious infections sensitive to Pencillin G
Gradual rise in resistance to Pen G
- use tetracycline
Definition
Infection of bone 2° blood-borne bacteria
Most common children
- peak 10 years
True haematogenous OM rare in adults
- usually involves spine
M: F 2:1
Most common femur & tibia
- initially affects metaphysis
- distal femur
- proximal and distal tibia
Blood Supply
- metaphyseal blood vessels penetrate physis
- blood vessels expand into large venous lakes at epiphysis surface
- transphyseal blood vessels persist to 1 year
- then physis becomes a barrier
Infection
- infection frequently occurs at epiphysis & in joint
- i.e. hip joint
- joint damage / growth disturbance
- profuse involucrum common
- usually resolves completely due to rich periosteal BS
Blood Supply
Nutrient artery supplies majority of metaphysis
- branch of nutrient artery reaches physis at right angle
- turn down in acute loops
- enter large venous lakes
Peripheral metaphysis / epiphysis have separate blood supply
Aetiology
A. Area of relative stasis near physis
- low oxygen tension
B. High amount of blood flow near physis
C. Trauma
- haematoma and oedema
Infection
Secondary thrombosis of nutrient artery
- periosteum lifts / cortex devascularised
A. Periosteum lays down involucrum
- periosteal new bone
- forms over cortex surrounding infected area
B. Cortical death / sequestrum
- entire cortex avascular
- inner 1/2 because of nutrient artery thrombosis
- outer 1/2 because of periosteal lifting
Epiphyseal involvement & joint infection rare
- growth disturbance rare
- increased blood flow to metaphysis may cause growth stimulation
Blood supply
After physeal closure, blood vessels again connect metaphysis and epiphysis
Infection
May occur in subarticular region & involve joint
Periosteal fibrosis / adhesion makes detachment by pus difficult
- prevents formation of subperiosteal abscess & preserves BS outer cortex
- thus large sequestra not formed
- hence infection spreads along shaft of bone
Secondary to bacteraemia
- history recent infection in 25%
Neonates
- E Coli
- Strep pyogenes
- Group B Strep
- S aureus
Children
- S aureus
- Hemophilus 18/12 - 3 years (unless immunised)
Adults
- S aureus
- G neg
Consider
- Gonnococcus (young adults)
- Salmonella (sickle cell)
- Pseudomonas (foot puncture)
- Fungal
Child
- usually delayed presentation
- history of trauma
- complaining of limb pain
- become febrile / unwell
- tender metaphysis
- may be red / swollen
Neonate
- mildly febrile / unwell
- refusal to move limb
- red / swollen limb common
ESR / CRP raised
WCC may be increased
Early blood culture before antibiotics
Bony changes at 10 days
1. First feature is periosteal new bone
- later involucrum
2. Brodies abscess
- osteolytic metaphyseal lesion
- well defined cavity in cancellous bone
3. Garre's osteomyelitis
- sclerosis and thickening of cortical bone
- partial obliteration of medullary cavity
- often diaphyseal
- consider anaerobe Propionibacterium acnes
Positive all 3 phases in 24 - 72 hours
- sensitivity & specificity 90%
Identify fluid in joint space which may be septic arthritis
Sequestrum
Increased signal on TI
Abscess
- high signal rim with low signal in middle
- rim / ring enhancement with gadolinium
Subperiosteal / intra-osseous
- positive culture in 60 - 90%
1. Antibiotics most effective before pus forms
- don't delay administration
- low threshold
- i.e. child with leg pain and likely early OM
2. Antibiotics can't sterilise avascular tissues or pus
- these should be removed surgically
80% will settle with antibiotics
Options
Flucloxacillin 25 - 50 mg/kg/dose q6h
Cephalothin 25 - 50 mg/kg/dose q6h
May be better to use broad spectrum
Route & Duration
Intravenous until child well, afebrile & non tender
- minimum 72 hours
- then convert to oral
- 24 weeks
- cease when CRP normal and child clinically well
Results
Peltola et al Pediatrics 1997
- 50 cases with change to oral at 4 days
- average duration 23 days
- effective treatment in all cases
Peltola et al Pediatr Infective Disease Journal 2010
- repeated same study
- same findings
Indications
1. Abscess
2. Sequestrum
3. Severely ill patient
4. Poor response to antibiotics ~24hrs
5. Diagnosis in doubt
Procedure
- tourniquet
- incision over maximum tenderness
- release of pus in ST & under periosteum
- drill-holes in cortex if no subperiosteal pus found
- close skin over drain
Septic arthritis
- < 12/12 old (blood vessels cross physis)
- intra-articular metaphysis i.e. hip
Septicaemia
Premature physeal arrest
Pathological fracture
Chronic OM
Recurrence 4%
Stage the infection, the host & the management
1. Stage host / maximise healing potential
2. Stage infection / MCS / sensitivities
3. Debride all infected bone and ST
4. Stabilise skeleton
5. Eliminate dead space
6. Soft tissue coverage
7. Eradicate infection
8. Deal with bone loss / obtain union
1. Secondary to acute osteomyelitis
2. Post traumatic
- usually following open fracture
- tibia most common
3. Post operative
- usually after implantation of prosthesis
- ORIF, total joint replacement
Anatomic
Host
Clinical
1. Anatomic
Type 1 / Medullary Osteomyelitis
- nidus is endosteal
Type 2 / Superficial Osteomyelitis
- secondary soft tissue breakdown
- infected cortex due to soft tissue defect
Type 3 / Localised Cortical & Medullary Osteomyelitis
- well marginated sequestration of cortical bone
- entire lesion can be excised without causing instability
Type 4 / Diffuse Cortical & Medullary Osteomyelitis
- involves entire segment bone
- unstable pre or post debridement
- infected non union
2. Host
Type A / Healthy
- good systemic defences
- good local vascularity and a normal physiologic response to infection and surgery
Type B / Compromised
- either local, systemic, or combined deficiency in wound healing and infection response
Type C / Not a surgical candidate
- requires suppressive or no treatment
- has minimal disability
- or for whom the treatment or results of treatment are more compromising than the disability caused by the disease itself
3. Clinical
I Simple dead space & simple closure
II No dead space & complex closure
III Simple stabilisations with complex dead space & closure
IV Complex stabilisations / closure / dead space
1. Bone erosion
2. Cortical & subperiosteal new bone formation
- cavities containing pus & sequestra
- surrounded by areas of sclerosis / reactive new bone
3. Soft tissue
- overlying soft tissue is usually indurated, puckered & adherent to bone
- often sinus connecting lesion to skin
Pathological fracture
- 2° bone destruction & brittleness
Malignant transformation ~ 1%
- sarcoma
- sinus epithelioid ca
Recurrent flares
- pain & fever
- redness / tenderness
Discharging sinus
Variable amounts of
- patchy lysis with surrounding sclerosis
- ± dense sequestrum
- bone can be deformed
Increased uptake in lesion
Shows bony architecture
Extent of bone destruction
- sequestra
- abscess cavities
Best to define extent of infection
Variable increase ESR & WCC with flares
Repeat MCS / sensitivity changes
Classical / Conventional method
- convert infected draining nonunion to non infected, non draining nonunion
- then obtain union
1. Stage host / maximise healing potential
2. Stage infection / MCS / sensitivities
3. Debride all infected bone and ST
4. Stabilise skeleton
5. Eliminate dead space
6. Soft tissue coverage
7. Eradicate infection
8. Deal with bone loss / obtain union
Most important in outcome
- control diabetes
- maximise nutrition
- cease smoking
M/C/S
Microbiology
- most common S aureus ~ 40 %
- 25 % mixed
- Gram negative 35 %
Removal of all dead bone
Treat infection like tumour
- meticulous debridement of necrotic tissue
Infected non union worst outcome
External fixation / Ilizarov excellent management
- gives stability
- eliminates metal at osteomyelitis site
- obtains union
- deals with bone defect
A. Antibiotic beads
- useful in cases unable to immediately graft
- can place flaps over the top & later remove beads
- allows staged bone grafting
B. Papineau open cancellous grafting
Concept
- leave open
- repeated bone grafting, dressings
- "grow bone up" to fill defect
Indications
- defects <4cm
- Type A patients
- stable defect
- subcutaneous bone
Timing of grafting
- depends on appearance of wound 3/52 after initial debridement
- return to OT at 3/52
- if clean --> graft
- if not further debridement
C. Muscle flap
Options
Usually muscle flap with SSG
- crucial to success
- fills dead space
- delivers blood supply / antibiotics / healing
Types
A. Local rotation flap
- gastrocnemius / soleus
- middle or proximal 1/3 tibia
B. Free vascularized flap
- lat dorsi / gracilis
Results
Smith et al J Plast Reconstr Surg 2006
- 10 year audit of 41 patients with chronic osteomyelitis
- 37 had free flap, remainder local muscle flap
- only 2 recurrences (4.4%) which where successfully treated with redebridement
IV Antibiotics
Repeated debridement
Timing
- usually delay 6/52
- let soft tissues settle, eradicate infection
Options
1. Autogenous cancellous bone graft
2. Autogenous vascularized
3. Structural allograft
- need elimination of infection
- useful in humerus
4. Bone Transport
Indications
- large defect > 4cm
Problems
- high rate of complications
- expertise required
Technique
- debride bone
- acute shortening or delayed docking
- proximal metaphyseal corticotomy
1. Dress sinus / drain acute abscess / suppressive Abx
2. Consider amputation
Joint inflammation secondary pyogenic organism
All age groups
Usually children
- 50% < age 3
M= F
Any joint
- Infants = Hip
- Children = Knee
- Adults = Large Joints
IVDU - SCJ & SIJ
Two Routes
1. Haematogenous
- distant focus
- seeds synovial membrane
2. Direct Extension
A. Osteomyelitis
- neonates & children
- from adjacent focus of OM
(i) Via Trans-physeal vessels in neonates
- Haversian & Volkmann's canals in children
(ii) Intra-articular metaphysis
- proximal & distal femur
- humerus
- proximal tibia
- ? distal fibula
B. Overlying Soft tissue Infection
C. Inoculation
- penetrating injury
- iatrogenic
Host
- immunodeficiencies
Joint
- previous joint trauma
- RA
- previous HCLA
Bacteraemia
Microbes vary with age
Neonates < 1/12
60% hospital acquired
- premature or unwell
- group B streptococci most common
- E coli & other Gram negative bacilli
- S aureus
Infants & Children <3 years
S Aureus
S. pneumoniae / pyogenes
H Influenzae
- reduced by immunisation
Children > 3 years
As above
Adults
S Aureus > Strep > G -ve
N. gonorrhoeae
- most common in young healthy adult / 70%
- may be polyarticular / associated with rash
- urethral swab / joint fluid PCR
- can treat with antibiotics alone
- usually no need for drainage unless fail to respond
IVDU - Gram negative
Community-Acquired
- S Aureus / MRSA
- Group B Strep
Kingella kingae
- Gram negative coccobacillus
- previously unrecognised
- because is slow and difficult to grow
- colonises nasopharynx, spread through blood stream
- take 14 days to culture
- put in specific BACTEC culture bottle
- sensitive to penicillin
Synovium oedematous & hyperaemic
- cloudy synovial fluid
> 2/7 frank pus
- cartilage destruction
- starts at areas of joint contact
Synovial membrane replaced by granulation tissue
- adhesions wall off pockets of pus
- fibrous ankylosis
Physis destroyed if intracapsular i.e. hip
- joint dislocation
- AVN femoral head
- Tom Smith OA
Cartilage Destruction
1. Proteolytic Enzymes
- Lysosomal - Collagenase / protease
- from neutrophils / microbes / synovium
2. Inflammatory cascade
3. Pressure
- degrades cartilage
- AVN / dislocation
Infant
History prior infection
- Eg umbilical sepsis
Irritability / failure to thrive
Low fever ~ Beware
Joint warm & swollen
Decreased active ROM
- pseudoparalysis
Intra-articular pressure high
- joints held in position to maximise joint volume
- hip abducted / flexed / ER
- knee flexed
Painful and decreased ROM
Child
As above
- easier to localise
Psoas sign
- pain on extension and IR
ESR
Erythrocyte sedimentation rate
- stickiness of RBC
- reflects fibrinogen concentration
- centrifuge blood tube and measure time to settle
- > 30
Not reliable in first 48/24 / Neonate / Steroids
Takes weeks to drop (3/12)
- lags behind resolution
CRP
Acute phase protein synthesised by liver
- > 10
WCC + differential
Elevate in 40 - 60%
- PMN leukocytosis
- left shift
Blood Culture
Positive 40 - 60%
Indications
- knee / ankle
- shoulder / elbow
- ASAP
Contra-indications
- neonate hip
- aspiration difficult & need GA
- drain ASAP
WCC > 50 000 per ml
Neutrophils > 75%
Gram stain Positve 30%
Culture positive 60%
Neonate Hip
- wide joint space
- subluxed
- 1° OM in metaphysis
Sequelae of hip septic arthritis
- Tom Smith's arthritis of infancy
- 6mth old with dislocated hip & normal acetabulum
- indicating recent onset injury to hip
- complete AVN of head
DDx focal metaphyseal OM
Identify AVN femoral head
100% sensitive at detecting fluid in joint
- useful to diagnose hip effusion
DDx
- OM
- psoas abscess
Transient synovitis v Septic Arthritis
Kocher criteria (for child with painful hip)
- fever
- Inability to weight bear on affected side
- ESR > 40
- WCC > 12000
4/4 criteria
- 99% chance that the child has septic arthritis
3/4 criteria
- 93% chance of septic arthritis
2/4 criteria
- 40% chance of septic arthritis
1/4 criteria
- 3% chance of septic arthritis
Infants & Child
1. Acute OM - Can get symptomatic effusion
2. Cellulitis
3. Transient Synovitis - Afebrile / ESR normal
4. Psoas abscess
5. JRA
6. Trauma
7. Perthes / SUFE in hip
8. Haemophilia
Adults
1. Gout
2. Pseudogout
3. RA / other inflammatory arthritis
Surgical emergency
- arthrotomy or arthroscopy
- Washout pus +++
- ± Synovectomy
- closure over drain
Hip
- anterior approach / Smith Petersen approach
- preserves blood supply to femoral head
- allows inspection of femoral metaphysis for OM
- between TFL and sartorius / G. med and RF
- 1 cm capsulotomy
- +/- drill neck (MRI useful to detect OM)
- leave capsule open
- close over drain
- assess hip stability
- may need brace or POP
Start after MCS
- start broad spectrum bacteriocidal
- gram stain as guide
Choice
- Flucloxacillin & Gentamicin adults
- Flucloxacillin & Ceftriaxone paeds
Timing
- IV AB until systemic toxicity & local swelling subside & CRP normal
- ~ 2/52
- usually continue oral antibiotics for further 4/52
Joint destruction - ankylosis / OA
Neonate Hips
- dislocation / subluxation
- destroyed epiphysis - Growth disturbance / LLD / coxa vara / breva
- absence of head / AVN
- pseudoarthrosis of femoral neck
Done by a grid system per HPF
- x40
- averaged over 10 fields
Normal
- 0-200
Non Inflamm (Trauma / OA)
- 50 - 500
Inflamm (RA / Crystals)
- 1500 - 50 000
Infection
- > 50 000
- exception is gonococcal arthritis
Standard now SI Units 10 x 106/ L
= 10 cells / mm3
= 10 x 103 /ml
= 10 x 103 /cc
= 10 x 105 /dl
= 10 x 105 /100ml
= 10 x 106 / L
Polymorph %
- normal 0-25 %
- non inflammatory = 0- 25 %
- inflammatory = 30- 70 %
- infection > 75 %
Viscosity
- will decrease as inflamation increases
- effect of hyluronate lost
- hence sepsis = Low viscosity
Glucose < BSL
± Crystals as acid Ph decreases solubility
- presence of crystals does not exclude infection
Gram stain positive 30%
Culture positive 60%
WCC > 50,000 + > 90% PMN leukocytes
- should be considered infectious regardless of the culture results
Fink Clin Rheum Dis 1986;12:423.
- large series of culture-proven cases of bacterial septic arthritis
- only 44% had cell counts > 100,000 per mm3
- 34% of cases having counts of < 25,000 per mL
Very rare
- Mainly affects children
Characterised by multiple osteomyelitic changes
- predominantly in metaphyseal region of long bones
All cultures negative
Antibiotics do not affect course of disease
Pain is most common symptom
- Occasional soft tissue swelling
Two or more radiologically confirmed bone lesions
Course of over 6 month, with exacerbations and remissions
Radiographic and nuclear scintigraphic evidence of osteomyelitis
Lack of response to over one month of antibiotic treatment
Lack of identifiable aetiology
ESR usually elevated (25 - 75 mm/hour)
CRP usually elevated (10 - 85 g/l)
White cell count usually unremarkable
Gamma globulins sometimes slightly elevated
Immunodeficiency tests normal
NSAIDs
Steroids may be of some benefit
Interferon used in severe cases
Usually protracted course
Usually self limited
Viral polyarthritis
Juvenile chronic arthritis
Acute osteomyelitis
Neoplasia
- Neuroblastoma
- Leukaemia
- Rhabdomyosarcoma
Langerhans cell histiocytosis
Fevers
ESR raised
Usually one site
2nd lesion may occur years later
Hot on bone scan
Same age group as CRMO
Histology
- chronic osteomyelitis
- Biopsy sterile
Lesions predominantly sclerotic
Recurrent symptoms
? Unifocal form of CRMO
From lung portal
Affects
- Epiphyses and metaphysis long bones
- also hands and feet
Amphotericin
As above
In immunocompromised
- HIV, Leukemia/lymphoma, DM
Produce radiolucent lesions with no periosteal reaction
Amphotericin B
Clostridial Myonecrosis
- necrotizing, gas producing infection of skeletal muscle 2° Clostridia
- life threatening & rapidly progressive
There are 3 types of bacterial gas-forming infections
1. Classical clostridial gas gangrene
- rapid onset of sepsis / couple of days
- muscle nearly always involved
- critically ill immediately following an open injury
- typically > 40° C
- pain & disorientation
- extensive myonecrosis
- brownish discharge
- extensive crepitus along the tissue planes
- requires amputation 1 joint above all involved muscle compartments & high dose penicillin
2. Streptococcal myonecrosis
- tissue-plane infection
- clinical evolution is slower / 3 - 4 days
- patients are not as critically ill as those with clostridial infection
- requires excision of all involved muscle compartments combined with open wound management and penicillin therapy
3. Anaerobic Gram negative gas gangrene
- necrotizing fasciitis
- common in diabetics with open ulcers
- usually polymicrobial
- requires open debridement combined with broad-spectrum antibiotics
Open Fractures
Penetrating wounds
War & Farmyard wounds
Surgical wounds - Bowel / Poor technique
Hypovascular limbs - DM / PVD
USA 1000 / year
- 0.05% of open fractures
Need 3 things
1. Necrotic tissue - especially buttock & thigh
2 Ischaemia with low PO2
3. Contamination with Clostridium
Greatly increased by
- poor debridement
- poor antibiotics
- 1° wound closure
Large gram positive rod
- does not produce spores
- obligate anaerobe
Ubiquitous (present in several places simultaneously)
- 20% of patient's skin
- commensal of GIT
- faeces in high concentrations
- coil
- common in hospitals
Saprophytic
- nutrition involving uptake of organic materials obtained from dead or decaying plant or animal matter
Exotoxins
- proteolytic or sacrolytic
- most important is A-Toxin (Lecithinase)
- + Haemolysin, Collagenase, Hyaluronidase, Leukocidin, Deoxyribonuclease, Protease & Lipase
Vicious cycle
- necrotic closed wound is contaminated with clostridium
- low PO2
- production of Histotoxins
- destruction of cell wall / local tissue death
- overwhelms WBC
Necrotic muscle
- reddish purple & friable
- becomes greenish purple
- gas in tissue
History
- develops within 24 hours of closure of a deep contaminated wound
- muscle penetrating injury
Pain out of proportion to injury or procedure
- alert & anxious
- patient in fear of death
Septic shock
- pale & sweaty
- moderate fever
- tachycardia + shock
- Delerium » Coma » Death
Wound
Early
- skin swollen & white
- tense oedema & local tenderness
- serosanguineous & brown discharge
- foul or sweet odour
- ± crepitus secondary to gas
Rapid progression
- bronze discolouration
- blebs containing dark fluid
- areas of green-black cutaneous necrosis
Clinical diagnosis
- positive blood culture in 15%
- gram-stain of exudate not helpful
- positive Nagler's test (Lecithinase turns egg yolk opaque in agar)
Gaseous distension of muscle & fascial planes
1. Anaerobic clostridial cellulitis
- clostridial infection of necrotic soft tissue
- poorly debrided wound
- gradual onset / slight toxaemia & no pain
- slight brown, seropurulent exudate
- foul gas +++
- no muscle invasion
2. Strept. myonecrosis
- group A ß haemolytic Strep pyogenes
- " Flesh-eating bug"
- similar to Cl myonecrosis / muscle dead
- patient not as critically ill
- minimal gas
- muscle debridement / open wound management / penicillin
3. Anaerobic cellulitis / necrotizing fasciitis
- subcutaneous emphysema
- pain, swelling, and toxemia usually remain minimal
- gas production may be abundant with a foul smell
- muscle compartments are not involved
- multiple Causative organisms
- Clostridia / anaerobic streptococci / Bacteroides / gram-negative rods
- debridement / broad-spectrum antibiotics
Awareness
- early meticulous debridement
- leave wound open
Appropriate antibiotics
- Kefazol
- + Gentamicin if extensive contamination
- + Penicillin if farmyard
Most important
- Delay = Death
Emergency exploration
- examine muscles directly
- differentiate Myonecrosis from Anaerobic cellulitis from Necrotising Fasciitis
Appropriate debridement
- radical myoexcision
- fasciotomies
- ± amputation
Penicillin high dose
- allergies - clindamycin
- beware penicillin resistance
- gentamycin for co-infection
High dose clindamycin
- may block Clostridial exotoxin
Fluid loss +++
- prompt replacement
- monitor fluid balance
Controversial
- bacteriostatic
- bactericidal
Hazards
- barotrauma
- decompression sickness
- convulsions
- otitis media
Useful where trunk involved
- may decrease margin needed
- 3 ATM for 1hr TDS for 2/7
- don't delay debridement to transfer to hyperbaric chamber
Mortality
- WWI = 50%
- WWII = 25%
Now lower
- 50% if reaches trunk
Elevated tissue oxygen tensions
Assists Neutrophils
- In hypoxic tissue
- require PO2> 40mmHg (5.3Kpa) for bacterial killing
Bacteriocidal to Anaerobes
Potentiates effects of Antibiotics
- Aminoglycosides
- Sulphonamides
- Trimethoprim
- Fluoroquinolones
- and Vancomycin in hypoxic tissues
Anaerobic fasciitis / Gangrene
- Reduce mortality when added to surgical debridement and Antibiotics
Complex diabetic foot
- reduces amputation rates in complex diabetic foot lesions including osteomyelitis
Crush injury
- shown to improve rate of healing and reduced re-operation in crush injury
Chronic Refractory Osteomyelitis
Usually use 2-2.8 Atmospheres
Need 6/52 to gain vascular ingrowth
Chronic granulomatous infection of skin & peripheral nerves by Mycobacterium Leprae
Endemic in some tropical regions
Commonest cause of peripheral neuropathy worldwide
Acid-Fast bacilli
- Carbol Fuchsin stain
- unable to be grown on artificial media
Virchow Cells
Vacuolated macrophages
Granuloma
Definitive route of transmission has not been proven
- is likely to be respiratory similar to TB
- broken skin transmission reported
Insidious onset
Involves
- skin
- superficial nerves
- nose, pharynx & larynx
- eyes
- testicles
Skin lesions
- pale anaesthetic macule 1-10 cm
- diffuse erythematous nodules 1-5 cm
- diffuse skin infiltration
Neurological disturbances
- nerve infiltration & thickening
- anaesthesia & paresthesia
- trophic ulcers & bone absorption
- short digits
- leonine Facies
- charcot joints
1. Lepromatous Type
Progressive malignant course
- characterised by severely impaired cell-mediated immunity
- late symmetrical polyneuropathy
2. Tuberculoid Type
Non Progressive benign course
- characterised by vigorous cell-mediated response
- anaesthetic skin patches
- thickened nerves
Bacilli seen in scrapings from skin or nasal mucosa
Culture Negative
Sulphone & Rifampicin for ~ 2yrs
Infection of skin and subcutaneous tissue
- spreads across fascial planes
- many microbes can be responsible
Type 1 Polymicrobial
Type 2 Monomicrobial
Group A Beta Hemolytic Strep (S. pyogenes)
- most common cause monomicrobial
S. Aureus / MRSA
Vibrio
- wound contaminated with saltwater
Clostridium
Anaerobes
Trauma
- insect bite
- skin laceration
- needle injection
- IVDU
Post operative
Diabetes
History of trauma / surgery / IVDU
Pain out of proportion
Skin
- initially swollen and red
- superficial nerves destroyed / skin anaesthetic
- becomes necrotic
Patient febrile and unwell / septic / in shock
- high temperatures
- altered levels of consciousness
Can distinguish between cellulitis and necrotising fasciitis
- increased T2 signal along fascia
High index clinical suspicion
Debridement of infected skin and subcutaneous tissue
- tissue and fluid sent for immediate MCS
- exclude myonecrosis
Broad spectrum
- penicillin / vancomycin
- becomes late problem
- patient may need extensive skin flaps
Mortality rates up to 25%
Clinical syndrome characterised by
Synovitis
Acne
Pustulosis
Hyperostosis
Osteitis
Unknown
- high prevalence of HLA B-27 antigen
- similarities to seronegative spondyloarthropathy
1. Severe acne or hidradenitis suppuritiva with osteoarticular disease
2. Palmoplantar pustulosis with osteoarticular disease
3. Axial or appendicular hyperostosis +/- pustular dermatosis (sternocalvicular hyperostosis)
4. Disease similar to CRMO
Sternoclavicular hyperostosis
Sterile inflammatory lesions
Hyperostosis & osteitic lesions may be similar to malignant conditions
Synovitis does not usually lead to bony erosions
Analgesics & oral anti-inflammatories
Favourable
- often protracted course with intermittent relapses & remissions without serious disability
Treponema Pallidum
Spirochete transmitted via
- direct contact with denuded epithelium
- transplacental infection
Primary
Macule at site of contact
- painless hard ulcer
- chancre
Secondary
4-8/52
- a rash (the most characteristic finding)
- fever / headache / malaise / anorexia
- diffuse lymphadenopathy
Tertiary
2-20yrs latency
Gummas / granuloma of skin, mucosa, bone, joints
Painless non tender swelling of long bone or skull
- may be diffuse sclerotic reaction resembling Paget's
Quaternary
Cardiovascular
- ascending aorta aneurysm
Neurosyphilis
- meningovascular - CN palsy, stroke
- general paresis of insane
- tabes dorsalis (sensory ataxia / numb legs / loss reflexes)
- charcot joints
- Argyll Robertson pupil
Congenital Syphilus
Presentation is multi-systemic, non-specific, variable
- 1/3 still birth
- 2/3 Present later
Metaphysitis / Osteitis / Periostitis
Pathological Fracture / Physeal separation
Nodes & Hepatosplenomegaly
Wimberger Sign
- erosion med prox tibial metphysis
Abuse
CRMO
Leukaemia
CMV
Rubella
Rickets
Bone Biopsy
- spirochaetes
RPR Rapid Plasma Reagin
- screening
Fluoroscent Treponemal Antibody Test
- confirmation
Lumbar puncture
- neuro-syphilis
Penicillin
- no reported resistance
- 100000 U/kg/D tds for 2/52
Congenital or acquired
- infection is localised to metaphysis and diaphysis
- doesn't cross into joint
Congenital Syphilis
- irritable and restless
- large, tender swelling around joint
- limb immobile
- cutaneous signs of syphilis may be present- skin lesions, mucous patches, and keratitis
X-rays
Show widening of metaphysis with marginal density and an indentation on its epiphyseal border
- diffuse periostitis
- with layers of new bone formation
- affected bone takes on a spindle shape with loss of metaph
Investigation
Serological markers not positive for 3/12 in neonate
- spirochete can be demonstrated on histology
Management
Responds well to Antibiotics
Late Stage / 2-3yrs
Characterised by osteoblastic activity
- a condensing osteitis
- mainly tibia, femur and skull
- subperiosteal bone formation produces characteristic prominent anterior tibia without bowing
- sabre tibia
Clutton's joints
- late stage of congenital syphilis
- 8-18 years
- recurrent bilat,eral painless effusions of knees
- aspirate shows high monomorph infiltrate
Definition
Caseating granulomatous mycobacterium infection
Great fall in incidence in West
- 1900 80% infected < 20
- 1990 5% infected secondary to immigrants
Found in
- asian immigrants
- aboriginal
- transplant patients 300 x Normal
- drug addicts
- AIDS
10% extrapulmonary
1% of skeletal
- half in spine
- mono-articular arthritis
2 species affect humans
1. M tuberculosis
- ? Bacilli
- most common
2. M bovis
- thin straight rods
Acid-Fast
- neither Gram positive or negative
- Ziehl-Neilsen Stain
- 2° to waxiness / high lipid in cell wall
Obligate aerobes
- prefer High PO2
Slow growth
- culture in Lowenstein-Jensen Medium
Produces no toxins or enzymes
Sensitisation
- occurs 2/ 52 after inoculation
- delayed cell-mediated, hypersensitivity
- positive Tuberculin test
- sensitised for life
Granulomatous Reaction
- initially Bacilli evoke non-specific neutrophilic inflammatory response
- phagocytosed by macrophages
- after sensitisation, reaction becomes granulomatous
- T cells become sensitised & induce macrophages aggregation
- granuloma formation
4 components to Granuloma
1. Epithelioid Cells
- resemble epithelial cells
- rounded & plump macrophages
2. Langhan's Giant Cells
- multinucleated, secondary to macrophages fusion
3. Rim of Fibroblasts
4. Central Caseous Necrosis
- liquefactive & coagulative
Primary Infection
TB enters body via
- lung (aerosol) (most important)
- gut (milk)
- conjunctivae or skin (rare)
Primary Complex
Infection of unsensitised patient
- lesion in upper region lower lung
- phagocytosed TB multiply in macrophages
- spread to regional nodes
- 1° or Ghon Complex
- usually no clinical illness
- heals with fibrosis / calcification
If doesn't heal, may progress to
- progressive 1° TB of lung
- haematogenous seeding / Miliary TB
Reservoir of bacilli in nodes
- can be reactivated
Secondary Infection
Infection in previously sensitised
1. Reactivation
- most common
2. Reinfection
Usually in apical lung
- high oxygen content of area
- AKA Simon's focus
Tertiary Lesion
Destructive extrapulmonary lesion from 2° infection
- multiple lesions in 30% (miliary)
- any organ involved
Initial infection usually asymptomatic
- slight malaise / fever
- lymphadenopathy
- pleurisy
Variable symptoms 2° TB
- fevers with night-sweats
- malaise
- weight loss
- cough / haemoptysis
Apical lesion
Multinodular infiltration with cavitation
Absolute proof is TB culture
Sputum
- early morning specimen
- bronchial washings
- multiple specimens
Ziehl-Neilsen Stain & Micro
- positive in 30%
Culture for 6/52
- positive in 80%
Mantoux test
- protein fraction of TB injection (0.1 ml injected into volar forearm skin)
- negative excludes diagnosis
- positive - previous sensitisation only or BCG immunization
Delayed hypersensitivity skin oedema in infected patients
Read 2/7
- delayed hypersensitivity
- positive > 10 mm
- negative < 5 mm
BCG Immunisation
- Bacillus Calmette-Guerin
- live attenuated strain of Bovine Tubercle Bacilli
- doesn't eliminate chance of infection
- prevents development of serious disease when infection occurs
- use questionable in areas with low incidence
- invalidates Mantoux
- prevents early detection
Isoniazid
- interferes with DNA synthesis
- side effects peripheral neuropathy / liver toxicity / anaemia
Rifampicin
- inhibits RNA synthesis
- SE's Jaundice / GIT symptoms / Fever
Protocol
- combination of Isoniazid & Rifampicin for 9/12
- other drugs for Resistant TB
Cause
- haematogenous seeding of synovium
- direct spread from bony abscess (unusual in that infection can cross physis)
Pathology
- synovium thick & oedematous
- marked effusion
- rice bodies formed ~ fibrin globules
- pannus of granulation tissue spreads across Joint
- gradual destruction of cartilage
- healing usually by fibrous ankylosis
History
- insidious onset
- long history of mild joint pain
- swelling & frequent effusions
- weight loss & night sweats
Examination
- thick synovium / effusion / lightly warm
- late FFD & deformity
- fibrous or bony ankylosis
X-ray
- joint becomes disorganized
- DDx Charcot joint
Management
- antibiotic
Epidemiology
L1 most often
- rare in cervical & sacral spine
- usually > one body
Pathology
Disco-Vertebral Lesion
Spread is most likely arterial
- not Batson's venous plexus
TB spreads to adjacent discs
- infection can then extend to involve multiple vertebral bodies
- posterior elements rarely involved
Bony Collapse
- result is sharp kyphotic deformity
- Gibbus
Para-spinal Extension
- usually anterolaterally
- abscess may burrow for long distances
- lumbar Abscess extends under Psoas fascia = Psoas abscess
- may extend into groin & thigh
- abscess may penetrate various organs esp Lung
Cord Compression / Injury
- pressure from abscess / caseous material / sequestrum
- ischaemia 2° spinal artery thrombosis
- progressive kyphosis
Clinical
Long history of ill health
Backache
Kyphotic Deformity
Cold abscess in loin or groin
Paraesthesia / weakness of legs (Pott's Paraplegia)
X-ray
- multiple vertebrae involved
- average 3-4
- collapse of adjacent bodies into each other
- resulting angular deformity
Bloods
- Mantoux +ve
- ± ESR raised
Management
1. Eradicate or arrest disease
- 9/12 Isoniazid and Rifampicin
- 90% favourable outcomes
- no advanatage debridement / bracing
2. Correct deformity
3. Prevent or treat paraplegia
Acute disease
- characterised by generalized rigidity & convulsions
- caused by exotoxins/neurotoxins produced in Clostridia Tetani infections
Annual world mortality is 1 million
West 15-100/year
Clostridium Tetani
- anaerobic
- spore-bearing Gram positive Bacillus
Spores
- drumstick appearance
- in faeces, dust & soil, manure
- especially hot damp climates
- resistant to antiseptics & heat
Infection
- occurs when spores enter tissues & produce vegetative forms
- entry through puncture / laceration
Tetanospasmin
- exotoxin released when vegetative bacteria lysed in wound
- potent neurotoxin
- spreads to CNS via PNS / BV / lymphatics
- blocks inhibitory pathways to cord
- muscle rigidity with paroxysmal spasms or convulsions result
Tetanolysin / haemolysin
Open fractures
Puncture >1cm
Foreign Body
Contamination / Tissue damage
Bite
Ischaemic / denervated tissue
Crush / burn / frostbite
Active Primary Immunization
- Tetanus Toxoid
- Triple antigen / Diphtheria-Tetanus-Pertussis / ADT
Children
- Triple Antigen at 2, 4 & 6 /12
- ADT at 18 /12 & 5 years
Adult
- for those never immunised
- 3 courses of TT
- 6-12 /7 between 1st & 2nd
- 6-12/12 between 2nd & 3rd
Booster
- ADT booster every 10 years
- if more than 20 years since booster, 2 boosters with 4-6/52 interval
After Injury 2° Prophylaxis
- if immunised, ADT will produce protective AB in 1/7
- if patient not immune full TT course
Passive Immunisation
- TIG / Tetanus Immuglobulin
- solution of Gamma-Globulin fraction of donated plasma
- give in tetanus-prone wounds in non immune patient
Mean incubation 1 / 52
- can be up to 2 months
- rapid onset = severe
Pain & stiffness
- Jaw / Abdo / Back
Difficulty swallowing
Generalised rigidity
- spinal extension & neck retraction
- upper limb flexion / lower limb extension
Clenched teeth expression / Trismus or lockjaw
Reflex spasms
- 2° external stimuli (eg. Noise)
Glottic spasms = Arrest
Sympathetic dysfunction
- HT, tachycardia, sweating
- arrhythmias, Ileus
60 % die in 2/52
- spasms disappear by 1-3 /52
- if survive, recover by 6 /52
- respiratory compromise is major cause of death
No specific tests
C. Tetani cultured in one third of wounds
- debride necrotic & contaminated tissue
- tetanus spores destroyed by AB
- vegetative form sensitive to AB
- 2 Million units q6h for 10/7
- a more concentrated TIG for treating clinical tetanus
- neutralises circulating toxin
- doesn't affect toxins already fixed in CNS
Spasms control
Quiet dark room
Diazepam
Consider thiopental infusion
Care of airway (may need ventolation)
Hydration & nutrition
1% of US population
0.1% of Australia
M:F = 20:1
Groups
- homosexual 80%
- IV User 5%
- heterosexual 8%
- haemophilia 2%
- blood transfusion 1.5 %
Unprotected Sex
Blood
- needle sharing
- blood products
- accidental transmission with infected blood in health care setting
Mother to Child
- pre or post natal
- breast milk
Retrovirus
- reverses RNA of virus into DNA
- incorporates into cell DNA
- uses reverse transcriptase
Immune impairment
- destroys CD4 lymphocyte / T Helper cell
Also affects
- B lymphocyte
- monocyte / macrophage cell line
- production of gamma interferon & lymphokines
- bactericidal functions of leukocytes
Wound healing
- via CD4 & lymphokine deficiency
Platelet deficiency
- via Autoimmune Thrombocytic Purpura
Neuropathy
- via Autoimmune Neuritis
May develop illness at time of acute infection
- seroconversion
- within 2-4 wks of exposure
- lymphadenopathy, myalgia, fever, rash
- viraemia (high transmission risk)
HIV Antibodies appear 3/52 to 4/12 after infection
Proportion will progress to AIDS
- median time of 8-10 yrs
- immune failure
- opportunistic infections
- neoplasms
1. Early (CD4 > 500)
- average survival 10 yrs
- develop autoimmune disorders
- ITP, Guillaine-Barre, Polymyositis
2. Intermediate (CD4 200-500)
- develop mild infections
- especially skin & mucosa
- Tinea, dermatitis, HSV
3. Late (CD4 < 200)
- average survival 2 years
- severe infections & malignancy
Window period
- usually 2-6/52
- > 6/12 considered safe
ELISA
- sensitive, but not specific
Western Blot Test
- specific
Opportunistic Infection
- Pneumocystis Carinii / Mycobacterium Avium complex (lung)
- Toxoplasmosis / Cryptococcal Meningitis (CNS)
Malignant Disease
- Kaposi Sarcoma
- NHL
- 1° CNS Lymphoma
Bacterial Infection
- increased susceptibility
- Pneumonia / CVL phlebitis / Cellulitis / UTI
Musculoskeletal Disease
Polyarthralgia - Self-limiting
Septic Arthritis - Prone to joint sepsis
Reiter's Syndrome
Polymyositis
Myalgia
Increased Complication rate
- impaired immune defence
- delayed wound healing
- increased morbidity and mortality from sepsis and wound problems
Rwanda Study
- post Op infection after ORIF
- HIV -ve = 5%
- HIV +ve = 0%
- AIDS = 23%
- CD4 < 250 = 11% Infection
- CD4 > 250 = 1.1% Infection
Preparation for OT
Consider
- immunologist & ID consultation
- Granulocyte-Stimulating Factor / Platelet transfusion
- treat infections
- stop marrow-suppressing AIDS treatments
Epidemiology
- 0.5% blood donors positive
NHx
- 20% carriers get cirrhosis at 20ys
- 5% get Hepatocellular Ca
Transmission
- Mainly IV Drug abuse
- Little evidence for sex spread
Needle-stick
- risk seroconversion is 3%
- only if patient HCV RNA +
- 30% of patients clear the HCV / will remain Antibody positive
Epidemiology
Australia has a mosaic incidence due to multicultural population
- Asia 10%
- Southern Europe 10%
- Northern Europe 0.1%
Transmission
- Extremely infectious
- IV Drug abuse
- sex
- Neonatal infection
Diagnosis
HBsAg +
- Currently infected & infectious
- Acute & Chronic Hepatitis
HBeAg
- Older marker of infectivity
Anti-HBc
- Antibody to core antigen
- Post infected immunity
Anti-HBs
- Vaccinated
- Post-Infection Immunity
HBVDNA
- Direct marker infectivity
- Acute & Chronic Hepatitis
Immune system produces antibodies against antigens
Immune system remembers
- second exposure to antigen generates greater & more rapid response
Two types of immunity
- humoral
- cell mediated
Two types immunization
- active
- passive
Lymphocyte precursors come from bone marrow
- migrate to modifying organ
- then return to nodes & bone marrow
Lymphocytes that populate thymus
Mediate cellular immunity
Differentiate into 4 types
1. Helper / Inducer T Cells (CD4)
2. Suppressor T Cells (CD8)
3. Killer T Cells (CD8)
4. Memory T Cells
Helper T Cells
- involved with regulation of antibody production by B cells
Killer cells
- destroy foreign cells
Cells that populate spleen & liver
Mediate Humeral Immunity
B lymphocytes differentiate into
- pasma cells
- memory B cells
Basic Process
Foreign proteins that enter body called antigens
- ingested by macrophages
- macrophages expose part of ingested antigen plus Major Histocompatibility Complex (MHC) on surfaces
Macrophages then contact lymphocytes
- CD4 (TH) cells bind to Antigen + MHC II on surface of macrophage
- CD4 cells become activated & contact B cells
- B cells activated
- proliferate
- transform into Memory B cells & plasma cells which secrete antibodies
Immunoglobulins
5 types
- shaped like Y
- stem is Fc Fragment
- arms are Fab Fragment
Consist of
1. Two light chains
- two types
- Kappa & Lambda
2. Two heavy chains
IgG
- Commonest
- Function is Complement fixation
- cross Placenta
IgA
- Function is localised protection secretions
IgM
- function is complement fixation
- immature Ig
- largest of the five
- can't cross placenta
IgD
- function is antigen recognition by B cells
IgE
- function is Reagin activity
- releases Histamine from mast cells
Located on short arm of Chromosome 6
- code Glycoproteins located on surfaces of all cells
- function in distinguishing self from non self
- three major loci
Class I Loci
- encode for HLA-A, HLA-B, HLA-C
- found on all cells except RBC
- primary factors in Self-recognition & Development of tolerance
Class II Loci
- encode for HLA-DP, HLA-DQ, HLA-DR
- involved in Antigen presentation to Helper T cells
- present on Antigen Presenting Cells
- macrophages, B Cells, activated T cells
Class III Loci
- encode for proteins of complement cascade
When antigens combine with circulating Ig
- cells lysed
- bacteria opsonised (phagocytosed)
- WCC attracted to antigen
- histamine released
Mediated by plasma enzymes called complement
- enzymes numbered C1 to C9
- C1 binds to Ig that have bound antigen
- triggers series of events that activates other components of system
- C3 facilitates phagocytosis of micro-organisms
- C5-9 inserted into cell membranes as pores
- C5a & C9a cause Histamine release from mast cells
- C5a is chemotactic for neutrophils
Mediated by CD8 cells
- activated when presented with antigen & MHC-I protein
Proliferate & differentiate into
- Memory T cells
- Cytotoxic T cells
- Suppressor T cells
Cytotoxic cells kill by
1. Insertion of pore-forming protein into target’s cell membranes
2. Insertion of toxins into target cells
Suppressor cells help to terminate immune response
Memory cells responsible for accelerated response to second exposure
Response of body to injury
Vascular Phase
- redness, heat & swelling
- transient vasoconstriction after injury
- then vasodilatation of arterioles
- increased permeability followed by plasma exuded into extravascular space
Cellular Phase
- leukocytes adhere to endothelium
- margination - migrate into extravascular space
Neutrophils
- attracted by chemotactic agents
- phagocytose bacteria, immune complexes & particulate matter
- particulate matter may be opsonised (coated with complement or IgG)
- opsonisation helps phagocytosis by aiding recognition
- during phagocytosis particle encased by vacuole
- lysosomes fuse with vacuole and enzymes destroy particle
Eosinophils
- Involved in host defence from parasitic infections
Mast Cells & Basophils
- involved in allergic or immediate hypersensitivity reactions
Macrophages
- important in chronic inflammation
- produced as monocytes in bone marrow
- function to phagocytose matter and present antigens to T Cells
Lymphocytes
- identify antigens
- help eliminate these antigens
- B Cells become plasma cells - humoral immunity (antibodies)
- T Cells mediate cellular immunity
Complement functions
1. Activation of inflammatory cells
2. Cytolysis of infected cells / insert pores
3. Opsonisation of antigen to facilitate phagocytosis
Kinins
- proteins that circulate in plasma in inactive form
- increase permeability blood vessels / Vasodilatation
- hypotension / pain / leukocyte margination
Histamine
- stored in mast cell granules
- released on activation by IgE
- produces increased BV permeability / vasodilation / bronchospasm
Serotonin
- stored in platelets
- causes vasoconstriction / increased BV permeability / fibrogenesis
Arachidonic Acid
- AA is a fatty acid found in most tissues
- released by phospholipases
Prostaglandins
Cyclo-oxygenase (COX) catalyses AA to PGG
- many types
- PGI2 (Prostacyclin) / Thromboxane A / PGE2
Effects of PGE2 & PGI2
- vasodilation
- increase BV permeability
- stimulate osteoclastic bone resorption
- anti-inflammatory effects
- inhibit T Cell activation
- inhibit B Cell proliferation
- inhibit IL-2 production
TXA2
- stimulates platelet aggregation
Leukotrienes
Lipoxygenase catalyse conversion of AA to Leukotrienes
- important mediators
1. Chemotactic for leukocytes
2. Activate neutrophil enzyme secretion
3. Increase BV permeability
4. Cause bronchospasm
Regulation
1. NSAID
- inhibit COX activity / inhibits PG synthesis
- suppress inflammation
- explains many of its side effects
- decrease cytoprotective effect of PGE2 on gastric mucosa (ulcers)
- increase leukotrienes (bronchoconstriction)
2. COX 2 selective
- don't inhibit COX 1
- maintain production of PGE2 in gastric mucosa
2. Glucocorticoids
- inhibit release of AA from phospholipids
- inhibit production of leukotrienes AND prostaglandins
Polypeptides that regulate inflammatory cells
- Interleukins
- IL-1, IL-6 & TNF
- similar actions
- produced by monocytes
Effects
1. Pyrogenic
2. Stimulate synthesis of Acute Phase Reactants
3. Facilitates B & T Cell proliferation
4. Stimulate stem cell growth for neutrophils & monocytes
IL-2 & IL-4
- stimulate proliferation of T Cells & IG production
- stimulate fusion of macrophages to form MNGC (multinucleated giant cells)
Il-3, Il-5 & Il-7
- promote growth & differentiation of haemopoietic stem cells
Interferon Gamma
- produced by activated T cells
- induces expression of Type II MHC antigens
- activates macrophages for antigen presentation
Acid Proteinases
- most stored in lysosomes of leukocytes
- degrade microbes & cell debris at low pH within phagolysosomes
- degrade extracellular proteins in connective tissue at neutral pH
1. Metalloenzymes
- require metal ions (eg Zn) as cofactor
2. Serine Proteinases
- collagenase - degrades extracellular collagen
- gelatinase - degrades denatured collagen
- proteoglycanase - degrades PG
Definition
Disease of unknown aetiology produces inflammation and muscle degeneration
Epidemiology
Begins in childhood
More common in females
Symptoms
Proximal muscle weakness
- muscles tender & swollen
- brawny & indurated
Arthralgias
- frequently hands, wrists, and knees
Starts with systemic symptoms
- skin rash, fever, malaise
Investigations
Creatine Phosphokinase elevated
Muscle biopsy
- inflammatory infiltration & necrosis
Xray
May see subcutaneous calcification
- classically seen in the proximal large muscles
- occasionally, the calcification assumes a sheet-like pattern along fascial or muscle planes
- is considered nearly pathognomonic for dermatomyositis
Management
Acute
- symptomatic
- corticosteroids
- immunosuppressive medication for resistant cases
Chronic
- physiotherapy
- orthotics
- surgical release of contractures
Epidemiology
Can occur at any age
- peak in childhood
- peak in late adulthood
- more common in females
Clinical Features
Similar to polymyositis
Rash more prominent
- photosensitive
- malar butterfly distribution
Management
As for polymyositis
Complications
Associated with neoplasm in 10-20%
Epidemiology
Middle aged women
Symptoms
Tender pectoral & pelvic muscles
Risk Temporal Arteritis
Investigations
ESR high
Management
Rapid response low dose steroids
Aetiology
Meningococcal arthritis
- most commonly
Streptococcal arthritis
- occasionally
Represents Arthus reaction
- interaction of newly produced circulating antibodies & bacterial antigens in synovium
- interaction produces immune complexes & inflammatory response
Aetiology
Unknown cause
- characterised by non-caseating granulomata
- can affect any organ at any age
Clinically
Most commonly affects the chest in young adults
- bilateral hilar lympadenopathy
- cough, fever, arthralgia, malaise, erythema nodosum
Also affects
- skin - rash
- eyes - uveitis
- heart
- CNS - hearing, balance
- renal
- MSK system
Two Musculoskeletal Forms
Symmetrical small joint polyarthropathy without bony involvement
- erythema nodosum
- hilar lymphadenopathy
Chronic granulomatosis bony involvement
- polyarthritis
- tenosynovitis
- punched out lucent bony "cyst"
- especially hand & feet
Definition
Autoimmune Disease
CREST Syndrome
1. Calcinosis
2. Raynaud's
3. Esophageal Strictures
4. Sclerodactyly
5. Telangiectasia
Clinical Features
Typical patient middle aged female
- cushingoid facies
Hands
Stiff shiny digits with loss of creases and flexion contractures
- autoamputation / acro-osteolysis - osteolysis of the tufts of DP (80%)
- punctate calcification of the terminal phalanx
- telangiectasia
- calcium nodules
Important to consider vascular supply to hand prior to OT
Extraskeletal
Lung fibrosis
CRF
Calcification (subcutaneous, extra-articular, occasionally intra-articular
Xray
Calcification in ST of digits
Osteopenia
Joint erosion
Investigations
DDx RA
- up to 40% scleroderma have positive RF
A chronic systemic, autoimmune inflammatory disease of unknown cause
1% of population
M:F = 1:3
Peak onset 40 years
Most common inflammatory arthropathy
Autoimmune
- trigger not identified
- cell mediated immune response
Combination of
1. External trigger ? Infection
2. Genetic susceptibility
Associated with HLA DR4
- 70 % RA
Shared epitope concept AA67-74 on Ag presenting gene
- marker of disease severity
- can have double dose of marker
Exogenous agent alters IgG to become antigenic
Plasma Cells produce RF directed against IgG
- synovium acts as lymphoid organ
- local plasma cells produce RF
- Antibody-Antigen complexes formed
- stimulate complement
- 2° destructive inflammatory cascade / lymphokines, IL1
IgM antibody directed at Fc region of IgG
- 80% with RA
- high titre correlates with severe disease
Present in 5% general population
- seen in SLE / Sjorgrens / TB / Syphilus / Hep c
1. Synovitis
- type B Synoviocyte undergoes almost malignant like transformation
- T Cell driven
- release metalloproteinases directly
- cartilage destruction
2. Synovial Fluid production
- predominate cell is PMN not lymphocyte
- PMN's amplify inflammation but synovitis is most important event in tissue destruction
3. Pannus
- proliferating synovium
- spreads over surface of cartilage
- causes direct destruction of cartilage
Most commonly present with
- malaise
- fever
- fatigue
Symmetrical pain & swelling in hands, wrists & feet
1. Slowly progressive polyarthritis
- gradually worsens over months
2. Episodic polyarthritis
- acute swelling of one joint
- resolves with asymptomatic interval
- intervals become shorter until polyarthritis develops
3. Monoarticular or Oligoarticular Arthritis
- swollen large joint
- polyarthritis develops later
4. Fulminating Polyarthritis
- elderly
- acute onset with widespread joint involvement
Short - Lived & No disability 25%
Mild Disability 25%
Progressive 40%
- variable progressive deformity
Severe 10%
- gross deformity / severe disability / rapid progression
Articular
- early morning joint stiffness
- joint swelling
- polyarthralgia - initially fingers, then wrists, feet, knees & GHJ
Systemic symptoms
- weight loss
- fever
- malaise
Nodules
- occur in 20% of patients
- pathognomonic
- associated with IgM RF
- most common occur on subcutaneous surface of forearms
- also pleura & lung / larynx / pericardium & myocardium / sclera
Ocular
- red eyes
- sceleritis / keratoconjunctivitis sicca
Pulmonary
- rheumatoid nodules
- if associated with pneumoconiosis / Caplan's Syndrome
- pleurisy
- diffuse interstitial fibrosis
Cardiac
- pericarditis
- nodules causing valvular insufficiency / conduction defects
Lymphadenopathy
- nodes draining affected joints
- nodes at a distance due to hyperactivity of RES
Myopathy
Neuropathy
- sensory polyneuropathy
- motor & sensory polyneuropathy
Cervical Myelopathy
- cord compression 2° atlantoaxial instability
- SMO / SAS
Entrapment Neuropathies
- CTS
- ulnar / cubital tunnel syndrome
Vasculitis
- obliterative endarteritis
- Raynaud's
Anaemia of Chronic Disease
- normocytic normochromic
Combination RA / Splenomegaly / Neutropenia
Other features are
- lymphadenopathy
- skin pigmentation
- chronic leg ulceration
- thrombocytopaenia
- haemolytic anaemia
Combination of
- dry eyes / keratoconjunctivitis sicca
- dry mouth / xerostomia
- connective tissue disorder - RA in 50%
Synovial Biopsy
- non specific chronic inflammation
Seronegative Spondyloarthropathies (Reiters / AS / Psoriasis / Enterocolitis)
Crystal Arthropathies (Gout / CPPD / HADD)
CT Diseases (JRA / SLE)
Polymyalgia Rheumatica
Sarcoidosis
Need 4/7 MAX RANS
1. Morning Stiffness
2. Arthritis of 3 areas > 6/52
3. X-ray changes
4. Rh factor
5. Arthritis of Hand > 6/52
6. Nodules
7. Symmetric Arthritis > 6/52
NSAID
First-line therapy
- alleviates pain & swelling
Side Effects
- troublesome
- skin rashes / gastric ulceration / renal dysfunction
Effects
Effective in 50-80%
- improve symptoms & signs in medium term
- some slowing of progress of disease
- toxicity is problem
Gold Salts
Inhibit monocyte function
- IM route / PO less toxic but less effective
- need close monitoring / toxicity in 30-40%
- pancytopenia & ARF
- screening with FBC & urinalysis
Penicillamine
Modulates lymphocyte function
- toxicity in 50%
- similar profile to gold
Antimalarials
Stabilise lysosomal membranes
- inhibit IL-1 function
- Chloroquine & Hydroxycholoroquine
- less life-threatening toxicity
- can cause macular degeneration
Sulphasalazine
Anti-Folate activity
- fewer side effects
MTX / Methotrexate
70% of patient respond
- main problem is pneumonitis
- more rarely liver fibrosis / marrow suppression
- 3-4% incidence nausea, stomatitis, nodules
Should MTX be stopped for surgery
- cessation can cause flare up which is difficult to treat
- without cessation risk of wound healing problems and infection
Effects
Dramatically effective
- long-term side effects - osteoporosis, HTN & DM
Indications
- refractory disease
- severe non articular manifestations of RA
Complications
- impaired wound healing
- increased risk of infection
- post-op hypotension
- wound dehiscence
- cover required by replacement of oral dose with IV Hydrocortisone
Effects
Modify the inflammatory cascade
Have dramatically changed the face of rheumatoid arthritis
Multiple studies demonstrating
- improved remission
- reduction in inflammation
- slowing of radiographic progression
A. TNF Alpha Antagonists
Etanercept, adalimumab, infliximab
- administered IV or subcut
- varying half lives
Side effects
- increased opportunistic infections
- TB, pneumocystis
- aspergillosis, candidiasis
Surgery
- unknown if increases infection risk etc
- recommend withhold for major OT
B. IL 1 Receptor Antagonists
Anakinra
Side effects
- nil obvious increase in opportunistic infections
Recommendations for surgery as above
1. Reiter's Disease
2. Ankylosing Spondylitis
3. Psoriatic Arthritis
4. Enteropathic Arthritis
Clinical overlap between them
- typically young men with asymmetric lower limb oligoarthritis
- associated with HLA B27
Definition
Reactive arthritis after veneral infection or dysentery
Young man with triad of
- oligoarticular arthritis
- urethritis
- conjunctivitis
Epidemiology
Almost exclusively young males
- M:F 10:1
- age 16-35 years
Aetiology
Obscure
- ? infectious trigger in genetically predisposed
- Shigella or Salmonella
- Mycoplasma or Chlamydia
HLA B27
- 75%
Clinical
Arthritis
- acute / asymmetrical
- usually knee & ankle
- settles after 2/52 & disappears after 3/12
- 50% have chronic disease
Tendonitis
- inflammation at tendinous insertions
- heel pain / plantar Fasciitis / achilles tendinitis
- back pain
Urethritis
- may be asymptomatic
Conjunctivitis & Iritis
Investigations
Raised ESR
HLA B27 75%
Definition
Inflammatory arthropathy associated with psoriasis
- 7% of patients with psoriasis
NHx
Often less aggressive
- typically DIPJ more involved
- may have less synovitis but bone and soft tissue destruction still occur
Classification
1. Classic - Involvement of DIPJ jts of hands
2. Deforming - with ankylosis & arthritis mutilans
3. RA like - similar to RA but without RF
4. Monarthritis
5. Ankylosing Spondylitis like
Pathology
Joint changes sim to RA
Spine & SIJ changes sim to AS
Clinical
Joints
- usually mild asymmetrical polyarthritis
- IPJ of hands & toes
Skin
- typical skin lesions of Psoriasis
- usually precede arthritis
- scaling erythematous papules
- scalp, elbows & knees
Nails
- 80% have nail changes compared with 30% with psoriasis alone
- pitting / subungual keratosis / transverse ridging
X-ray
Hands
- periarticular phalangeal erosions along phalangeal shaft with scalloping
- P3 tuft resorption & whittling (acro-osteolytis)
- typical 'Pencil in cup' deformity of DIPJ
SIJ
- indistinguishable from AS
Large joints
- similar to RA
Treatment
Similar to RA
Definition
Inflammatory arthropathy associated with IBD
- Crohn's
- Ulcerative Colitis
Incidence
Arthropathy in 15% of IBD
Spondyloarthropathy in 5% IBD
Clinical
Peripheral arthritis
- acute migratory attacks ~ 1 / year
- associated with flare of IBD
- affects large joints
- transient / lasts < 1 month
- non-deforming
- synovitis only
Spine
- classic AS
- persists if present
- treatment IBD does not treat spinal symptoms
Treatment
Treatment of IBD causes arthritis to abate
- sulphasalazine effective
Systemic Connective Tissue Disease
Chronic inflammatory disease resulting from abnormal immunoregulation
Unknown
Thought similar to RA
1. Genetic factors
2. Environmental factors
Young females
F:M 9:1
Peak 35 years old
Geographic variations
- more common in black and asian populations
Affects many organ systems
- bones / joints / tendons / skin
- heart / kidney / CNS
Systemic
- malaise / fever / anorexia / weight loss
- skin rashes / photosensitive butterfly rash
- Reynaud's Phenomenon / peripheral vasculitis
- splenomegaly
- largest cause of mortality is CRF
Joint involvement
Presenting complaint in >90%
- red swollen joints
- usually involves small joints & knees
- symmetrical involvement
Morning stiffness in 50%
Longstanding disease may produce RA like deformity
AVN
Predisposes to bone ischaemia
- aggravated by steroids
- classically in talus
1. No ankylosis or contractures
2. No erosive changes on xray
3. Less destructive than RA
ANA positive / antinuclear antibodies
- screening tool
- positive in other CT diseases and normal people
dsDNA / anti double stranded DNA
- highly specific for SLE
C3/C4
- low levels complement secondary to consumption
antie-ENA / anti extractable nuclear antigen
Elevated ESR
Anaemia / Leucopaenia / Thrombocytopaenia
Avoid sunlight as it exacerbates symptoms
Options
NSAIDS
Steroids
Cyclophosphamide
DMARDS
Anti-immune as per RA
IV immunoglobulin
Higher risk of deep infection
HIV
Risk seroconversion
- 1 in 250
- 50% less with gloves & blunt needle
US Public Health Service Guidelines
- recommend 2 drug therapy for 4 weeks post exposure (AZT and 3TC)
- consider if patient's virus is resistant, and change medications accordingly
Hepatitis C
Seroconversion risk varied reports
Kubitschke et al Internist 2007
- systematic review
- average rate of seroconversion 0.75%
US Public Health Service Guidelines
- do not recommend prophylaxis post exposure
Management
- wait to see if seroconvert
- 2/3 will eliminate HCV RNA
- otherwise can use interferon
Hepatitis B
Most likely to seroconvert if not immunised
- 20%
Sharp injury in 1.3 - 15.4% of operations
- half from suture needle
Mucous membrane contamination
- facial 100% in THR
- risk unknown
1. Wash wound +++ with betadine
2. Take blood for serology from health care worker
- repeat at regular intervals
- important for management
- important for insurance
3. Take blood for serology from patient
- history of risk / exposure
- consent obtained
- need to repeat at 6/12
Universal Precautions
Known infective status of patient
- warn OT staff of status / risks
- maintain confidentiality
- minimal equipment
- ergonomic setup
- most experienced staff & surgeon
- glasses / hood
- impervious disposable gowns & drapes
- boots
- universal precautions
- double gloves
- taperpoint needles & staples
- single suturing surgeon
- instrument only technique
- sharps tray
Screening HCV & HBV in high risk groups
- of dubious value
- windown periods for HIV
Eduction
Life Style Modification
- vocational Counselling / ergonomic work environment
- activity modification
- home modifications
Pharmaceuticals
- symptomatic
- disease modification
Orthotics
Physiotherapy
- local symptomatic
- range of motion
- strengthening
- functional re-education
Injections
- HCLA
Non-union
- arrest of progression to union at fracture site
- > 6-9 /12
- no visible progressive signs of healing for at least three consecutive months
- individualise for each fracture
- when the surgeon believes the fracture has little or no chance to heal
Delayed union
- failure of fracture to unite within expected time
- still may spontaneously unite
Phases
- haematoma / inflammation / neoangiogenesis
- soft callus
- hard callus
- remodelling
Haematoma
- immediate at site of injury
Inflammation
- vasodilation & exudation of plasma & leucocytes
- polymorphs, histiocytes, & mast cells appear
- process of removing debris begins
Neoangiogenesis
- rapid development of an extra-osseous blood supply
- derived from surrounding soft tissue
- invasion of fibrovascular tissue that replaces the haematoma
- lays down collagen & matrix that later becomes mineralised to form woven bone (provisional/ primary/ soft callus)
Soft callus
- primary callus response within days / weeks
- inner cambrial layer (as opposed to outer fibrous layer) of periosteum
- surrounding soft issue fibroblasts
- forms fibrocartilage matrix
Hard callus
- external bridging callus within weeks
- woven bone formed by mineralisation of fibrocartilage matrix
- arises most probably from osteoinduction of cells which do not have direct connection with bone
- blood supply reliant on surrounding soft tissue
- primary purpose is to arrest movement between bone fragments
- strong evidence it arises from by bioelectric feedback (piezoelectric effect)
Remodelling
Bone remodelling in response to local stress / strain in accordance to Wolff's Law
Primary Bone Healing
Anatomical reduction and absolute fixation
- no gap, no strain
- no callous is form
- intramembranous ossification (osteoid onto CT membrane)
Creeping substitution
- advancing front of osteoclasts
- osteoclasts form cutting cones across cortical bone allowing revascularisation
- followed by osteoblasts laying down bone matrix
- endosteal callous is formed
Secondary Bone healing
Normal phases of bone healing
- endochondral ossification
- mineralisation of fibrocartilaginous matrix
- soft and hard callous
Differentiation of mesenchymal tissue into bone, cartilage or fibrous tissue
A. Intramembranous ossification
- in areas of low stress / strain
- mesenchymal stem cells
- no cartilage stage
- osteoid secreted onto CT
- woven bone
- eventually becomes lamellar bone
B. Endochondral ossification
- low to moderate tensile strain & hydrostatic tensile stress
- chondrocytes make cartilage
- osteoprogenitor cells become osteoblasts and secrete osteoid onto calcified cartilage matrix
C. Chondrogenesis
- if hydrostatic compressive stress or poor vascularity
D. Fibrous tissue
- if high tensile strain
E. Fibrocartilage
- if tensile strain with hydrostatic compressive stress
Different tissue can tolerate different amounts of strain
- Fibrous ~ 100% strain
- Chondroid ~ 20% strain
- Bone < 2% strain
Interfragmentary strain (motion) is inversely proportional to the fracture gap
- small gap with small motion --> large strain
- large gap with small motion --> small strain
Bone resorption may decrease strain & hence allow granulation tissue to form
- then the callus will stabilize the fracture enough to allow the next stage to progress
- hence amount callus proportional to stability
Patient factors
Injury
Treatment
Patient factors
Age
Activity
Immoderate, noncompliant patient
Nutrition / catabolic states
Anaemia
Smoking
- decreases peripheral O2 tension
- dampens peripheral blood flow
Alcohol
DM
Peripheral Neuropathy
Immunocomprimise
Osteomalacia
- failure to mineralise callous
- correct abnormality
Pharmacological agents
- Steroids
- Cytotoxics
- Ciproflaxacin
- NSAIDS
- Irradiation
Giannoidin et al JBJSB 2000
- 32 unions and 67 non-unions
- NSAID use significant
- delayed healing in united group also
Injury
Open fracture
Significant soft tissue trauma
Soft tissue interposition
Infection
- inflammatory response
- disrupts callous, increases fracture gap and motion
Pathological fracture
Malignant tissue
Osteoporosis
Anatomic Location
- Poor vascularity / NOF / scaphoid / 5th MT
Intact fellow bone
Excessive bone loss
Segmental injury
Comminution
Displacement
- shown to be important in the tibia
Synovial fluid / Intra-articular
Treatment
Distraction of fracture
Inadequate stability with excessive movement
Extensive approach with vascular compromise
No axial load
1. Hypertrophic
- elephant foot (abundant callous)
- horse hoof (less abundant callous)
- adequate vascularity, poor mechanical environment for healing
- predominantly fibrocartilage in gap
- inadequate stabilization / excessive strain
- 92-95% non-infected non-unions tibia & fibula
2. Oligotrophic
- no callous on x-ray
- vascularity on bone scan
3. Atrophic / avascular
- pencilling of bone ends
- avascular
- no vascularity on bone scan
- fibrous or cartilage interposition
- needs osteoinduction + stabilization
- debride non-union / rigid fixation / compress / bone graft
4. Pseudarthrosis
- non-union with fluid-filled cavity
- synovial-like membrane & pseudocapsule formation
- new joint at fracture site
- usually painless motion
- needs excision of pseudoarthrosis / rigid fixation / compression / bone graft
1. Rigid stabilization
2. Autograft / allograft
3. Other modalities
- Electrical stimulation
- US therapy
- BMP
- Bone marrow aspirate
Science
Based on principle that bone healing primarily occurs as a result of strain-generated electrical potentials
- no effect on fully fibrous non-union
- must have some biological process occurring
Three types
1. DC
- negative pole (cathode) has to be implanted into fracture site
- produces sustained injury potential that increases inflammatory respons
- invasive / risk infection
2. AC
- use conductive medium
- paste electrode either side of affected extremity
- only work on soft & hard callus
- increase cAMP, collagen synthesis & calcification during soft & hard callus stages of healing
3. Pulsed Electromagnetic Fields
- most used clinically
- placed externally without need for inductive media
- electrodes either side of non-union in cast or brace (no need to contact skin)
- can be symmetrical or asymmetrical pulse
- help convert soft to hard callus
Results
Simonis et al Injury 2003
- RCT of electrical stimulation v placebo in tibial non union
- increased union rate in smokers from 67% to 100%
Sharrard JBJS Br
- RCT of 45 tibial delayed union
- significantly improved union rate c.f. control
Science
Ultrasound is acoustic radiation at frequency above human hearing
- mechanical energy that can be transmitted into the body as high-frequency pressure waves
- micromechanical strains may promote bone formation in same manner as postulated by Wolff's Law
Exact mechanism unknown but may be
- enhanced production of osteoinductive agents
- direct stimulatory effect on osteoblasts
- increased blood supply
Results
Exogen Registry
- 1700 delayed unions 91% healing rate
- 700 non-unions 85% healing rate
Heckman JBJS 1994
- prospective, double-blind, randomised, placebo-controlled trial
- closed or grade 1 open tibial diaphyseal fractures
- all US patients healed (average 96 days) vs some nonunions in placebo group (average 150 days)
- healing times reduced in smokers
Science
See Miscellaneous / Bone graft
Results
Friedlaender et al JBJS Am 2001
- as efficacious as autograft in established tibial non union
Govender et al JBJS Am 2002
- RCT of control v BMP in open tibial fractures
– less secondary interventions, accelerated time to union, reduced infection rates
Jones et al JBJS Am 2006
- RCT allograft + BMP2 v autograft in tibial diaphyseal cortical defects
- similar rates of healing, reduced blood loss in BMP group
Garrison et al Cochrance Database Review 2010
- limited evidence for BMP in acute fracture
- unclear evidence in non union
- likely economically viable in severe open tibial fractures
Results
Hernigou et al JBJS Am 2006
- 20mls BMA injected percutaneously into 60 atrophic tibial non unions
- union obtained in 53 cases
No accepted definition
Chronic joint disorder in which there is progressive softening and disintegration of articular cartilage
- accompanied by new growth of cartilage and bone at the joint margins
- these changes secondary to mechanical failure of hyaline cartilage
Essentially no inflammatory component
Primary
Idiopathic
- cartilage degenerates in all as time goes by
- high incidence of cartilage wear & OA in 7th decade
Traumatic
- fracture / meniscectomy / instability / limb malalignment
Infection
Tumour
- PVNS / synovial chondromatosis / lipoma arborescens
Inflammation
- RA / spondyloarthopathy / CT disorders (SLE, sarcoidosis, scleroderma)
Metabolic
- gout / pseudogout / haemochromatosis / onchronosis
Neuromuscular
- charcot
Endocrine
- acromegaly / Paget's
Development
- SUFE / DDH / Perthes/ skeletal dysplasias
Prevalence
- rises steeply with age
- 15% at 40
- 75% at 70
- > 50% have symptoms
1. Abnormal forces on normal cartilage
Force = Load / Unit area
Increased Load - obesity
Decreased contact area - subluxation / ankle diastasis
2. Normal forces on abnormal cartilage
Age
- cartilage more stiff / less strong & elastic
- hypocellular
- decreased water content
Increased Stiffness
- ochronosis / CPPD / HA deposition
Increased softness
- chronic Inflammation
Cardinal Features
- cartilage disintegration
- subchondral cysts
- subchondral sclerosis
- osteophyte formation
- capsular fibrosis
1. Collagen network damaged
- disorganised & loosened
2. Loss of Proteoglycan
- leach from matrix
- decreased Chondroitin : Keratin
3. Increase of water
- as a result of above the water content increases
4. Cartilage swells
- less stiff and more prone to damage
- increased permeability
5. Chondrocyte damage
- IL1 released from synovium & chondrocytes
- IL1 important mediator of metalloproteinases
- collagenase breaks down collagen
6. Cartilage damage
- attempt at repair
- hypermetabolic state
7. Subchondral Bone
- increased force transmitted to bone
- result is increased mechanical strain on overlying cartilage
- precipitates cartilage degeneration
8. Subchondral Cysts
- ? caused by stress fractures / focal AVN / synovial fluid pumps through cracks
9. Osteophytes
- result of piezoelectric forces from abnormal stress
- increase surface area of joint
Monoarticular or Pauciarticular OA
Pain & dysfunction in 1 or 2 of the large weight bearing joints
Secondar OA
- OA single joint from previous problem
- most common is knee post meniscectomy
Hip OA
- secondary to mild dysplasia
Polyarticular OA
Usually middle-aged woman
Hands
- pain, swelling & stiffness in fingers
- characteristic knobbly appearance of IPJ
- from osteophytes & ST swelling
Often affects knees
- medial & PFJ compartments
Also
- base of thumb
- MTPJ of hallux
- facet joints
Rapidly Destructive OA
Rapidly progressive loss of joint space
- usually affects hip
1/3 caucasian women > 64
Insufficient bone mass at time of skeletal maturity
- peak bone mass is achieved at age 25
Rapid loss of bone after menopause
Low body weight / weight loss / history of smoking / steroids
Type 1
- postmenopausal
- high turnover / osteoclast mediated
- F x 6
Type 2
- age-related / senile
- low turnover / osteoblast mediated
- F x 2
Can have both
DDD NICE
Disuse
- prolonged bed rest
- inactivity
- paralysis
- space travel
Diet
- low calcium, insufficient vitamin C
- anorexia nervosa
Drugs
- heparin
- methotrexate
- ethanol
- steroids
Neoplasms
- metastatic disease
- myeloma / lymphoma / leukemia
Idiopathic
- adolescent (10-18 years)
- middle-age men
Chronic Illness
- RA / cirrhosis / sarcoidosis
Endocrine Abnormalities
- DM
- pituitary hypersecretion
- adrenal cortex excess
- ovary- oestrogen deficiency
- testis - testosterone deficiency
- hyperparathyroidism
- hyperthyroidism
Definition
Dual Energy X-ray Absorptiometry
- hip and spine
Method
Compare bone mass values
- to ideal peak bone mass in pool of peers / young people
False negatives
- osteophytes in hip or spine
Grading
Within 1 SD of ideal
- normal
1 – 2.5 SD below ideal
- osteopenic
>2.5
- osteporotic
> 2.5 + fragility fracture
- severe, established osteoporosis
Scores
T score
- SD below young adult at peak bone density
Z score
- SD below average person of same age
Exclude secondary causes
Neoplasm
- multiple myeloma (se electrophoresis)
Endocrine
- hyperparathyroidism (Ca, PO4, PTH)
- hyperthyroidism (TFT, T3, T4)
- Cushing’s / CRF (U&E)
- DM (glucose)
- osteomalacia (low Ca, Vit D)
- FSH / LH / T
Wrist fractures
Hip fractures
Vertebral fractures
Sacral insufficiency fractures
Adequate calcium and vit D
Adequate weight
Exercise
No smoking
Basis
Quite often have inadequate calcium intake
- need 1500 mg / day
- patents develop osteomalacia with secondary hyperparathyroidism
Effect
Reduces rate of bone loss
- very cost effective
- supplement with vit D
Physiology
- 25 hydroxy Vitamin D ingested
- alpha-hydroxylation in kidney to 1,25
- 1,25 dihyroxy D is active form
- enhances absorption of GIT calcium
Treatment
Calcitriol (1,25 dihyroxy Vit D)
Effect
Salovaara et al J Bone Mineral Research
- RCT of vit D3 and calcium v placebo in 3500 women > 60
- 3 year follow up
- reduced distal forearm fractures by 30%
- no effect on incidence lower limb fractures
Method
Osteoblasts have receptors for estrogen
Menopause
- skeletal bone loss increases 2% per year
- 8% cancellous
- 0.5% cortical
Results
PEARL trial of Lasofoxifene in postmenopausal women
- reduced risk of CAD and CVA
- reduced risk of breast cancer
- increased risk of thromboembolic events
Cummings et al N Eng J Med 2010
- RCT of 8550 women lasofoxifene v placebo
- significantly improved BMD
- reduced rates of vertebral and non vertebral fracture
- reduced rates breast cancer, CVA and MI
Action
- binds to osteoclast
- decreases their number and activity
Administration
- nasal spray
Problems
- 22% people develop resistance
Effects
Kaskani et al Clin Rheumatol 2005
- RCT of calcitonin v vit D3
- calcitonin increased BMD at 1 year
Tascioglu et al Rheumatol Int 2005
- RCT of calcitonin v aledronate
- aledronate significantly better improvements in BMD
Action
Pyrophosphate analogs
- bind to surface HA crystals
- inhibit osteoclast resorption
Indications
Low energy fracture
T score > 2.5 below
Side effects
Indigestion 30%
Occasional diarrhea
Bone pain (remedy by giving calcium at same time)
Very rarely jaw necrosis at high doses IV
Etidronate
- increases risk GI ulceration and bleeding
Atypical femoral fracture related to bisphosphonates
- reports of atraumatic bilateral femoral fracture
- seen in women taking bisphosphonates for more than 5 years
- insufficiency fracture
- characterised by short oblique subtrochanteric and diaphyseal fractures
- typically see lateral cortical thickening / sclerosis / beaking before the fracture
- must check contralateral femur if have a fracture
- xray any patient complaining of thigh pain
- recommend drug holidays to prevent this complication
Doses
Aledronate / fosamax 70 mg weekly
- must take on empty stomach, with no food for one hour
IV risedronate
- take only once per year
Results
Harris et al JAMA 1999
- RCT of oral risedronate v placebo 2500 women with history vertebral fracture
- reduced risk of vertebral fracture by 40%
- reduced risk of non vertebral fracture by 40%
- increases BMD at vertebrae by 5%
- prevents loss of BMD at femoral neck
Chronic, non metabolic bone disorder
Characterised by increased bone resorption, bone formation and remodelling
Rare < 40
1 – 3 % population over 60
M > F
Unknown
Paramyxovirus implicated
- measles
- RSV
- canine distemper virus
Electron Microscope
- viral like inclusion bodies in osteoclasts
No presence of specific viral antibodies
Intense focal resorption of normal bone by abnormal osteoclasts
- primary abnormality
- osteoclasts large, very active, numerous with excess nuclei
- make large resorptive cavities in bone matrix
In response, osteoblasts recruited
- activity very rapid
- because of this, newly formed bone is not organised and remains irregular and woven in nature
- less resistant and more elastic
- prone to deformity and fracture, especially in weight bearing extremities
3 phases
1. Initial short lived burst of multinucleate osteoclastic activity, causing resorption
- this phase has marked elevation of serum alkaline phosphatase level
2. Mixed phase of both osteoclastic and osteoblastic activity, with increased bone turnover
- leads to structurally abnormal bone
3. Final sclerotic phase
- bone formation exceeds bone resorption
Monostotic 25%
Polyostotic 75%
Pelvis
Lumbosacral spine
Femur
Tibia
Usually incidental x-ray or elevated alk phosphatase
Bone pain
Bone deformity
Fracture
Arthropathy
- incidence may be no higher than normal population
- patterns are different
- i.e. coxa vara and protrusio in hip
Neurological complication
- deafness / involvement of petrous temporal bone
- cranial nerve palsy
- spinal cord compression
Pain / sarcomatous transformation
- beware patient with increasing pain / fracture
- may develop OS in tibia / pelvis
All three stages may be present in same patient and same bone at same time
First stage
- lytic areas
- osteoporosis circumscripta cranii
- less commonly in long bones (advancing V shaped lytic lesion)
Third stage
- dense sclerosis
Deformity
- sabre tibia
- coxa vara / protrusio hip
- skull (leonine)
Shows increased uptake
Diagnosis
- urinary hydroxyproline levels
Calcium
- may be elevated after bed rest
ESR
- may be elevated in malignant transformation
Serum alkaline phosphatase
- enzyme on osteoblasts
- good indicator of activity
Rarely needed
Predisposes to fracture
Mosaic pattern of poorly organised lamellar bone
Mulitnucleated osteoclasts
Indications
Bone pain
Neurological symptoms
Long bones with risk of fracture
Risk of spinal neural compression
Preoperative
Bed rest induced hypercalcaemia
Aim
Reduce alk phos to normal
Results
Reid et al N Engl J Med 2005
- RCT of single infusion of risedronate v 30mg per day for 30 days
- reduction of Alk Phos at least 75% as end point
- faster, more complete and longer lasting effect with IV infusion
- good therapeutic response in both groups
Miller Am J Med 1999
- RCT comparing risedronate to etidronate
- risedronate had better and longer lasting remission
- also had more significant reduction in pain relief
DDx
- fracture (tension side)
- bone pain (treat with bisphosphonates)
- hip OA (confirm with intra-articular HCLA)
- tumour
Surgical issues
Bleeding
- known to have excess bleeding
- reduce vascularity with medical treatment
- use cell saver
Hard bone
- difficult reaming and broaching
- may need burrs to enter femur
Cement v Uncemented
Protrusio
- medial bone graft, lateral offset liners +/- antiprotrusio cages
Fracture
- intra-operative and post-operative
HO
- may need prophylaxis
Results
Lusty et al J Arthroplasty 2007
- 23 THR in Paget's followed on average for 6.5 years
- 1 aseptic loosening
- 2 periprosthetic fractures
Surgical issues
Bone very hard and deformed
- difficulties with IM and EM jigs
- navigation may be advantageous
Corrective osteotomy
- may be required
- in tibia especially
- metaphyseal best site for healing
- healing times are probably delayed
Results
Lee et al J Arthroplasty 2005
- 17 TKR followed up for 9 years
- 1 revision for aseptic loosening at 10 years
- no deep infection or substantial HO
Platelet rich plasma
2 main components
1. Platelets
- contain PDGF, TGF, VEGF
2. Growth factors
- ILGF
- FGF
Formed from the separation of whole blood into plasma and RBC
- separation usually achieved with centrifugation
Platelet concentration
- whole blood 150 - 400 x 106 / ml
- up to 8 x higher in PRP
- region of 600 000 to 1000 000 platelets per ml
Draw 2 amounts of blood
- 60 mls to be centrifuged to PRP, mix with anticoagulant
- 8 mls to provide thrombin, mix with anticoagulant
Sit for 60 minutes
Centrifuge for 15 minutes
PRP
- draw off plasma
- take PRP
Thrombin
- remove from small tube
Use premade injection device as required
Lateral epicondylitis
Peerbooms et al Am J Sports Med 2010
- RCT PRP v HCLA
- improved outcomes at 6 months and 1 year in PRP
Rotator cuff tears
Muscle Tears
Tears
- hamstring
- adductors
- iliopsoas
- gluteus
- abdominal oblique
- gastrocnemius
No Level 1, 2 or 3 evidence
Acute Tendon / Ligament Injuries
Acute Injuries
- MCL tear
- lateral ankle ligament rupture
- achilles tendon rupture
Chronic Tendon / Ligament Injuries
De Vos et al JAMA 2010
- RCT in achilles tendinopathy
- PRP v saline
- no difference in outcome
Black population
- heterozygote protective from malaria
- AD
Abnormal peptide substitution in ß chain of Hb
- HbS
Homozygous 1%
- HbSS
- sickling occurs with relative hypoxia
- trapped in blood vessels
- necrosis & pain
Heterozygous 8%
- sickle cell trait
- Hb SA
- sickling only with extreme hypoxia
High risk of pneumococcal septicaemic and meningitis
1. Vaso-Occlusion
Suffer recurrent crises of abdominal & bone pain
- bone crisis
- finger pain
- can get bone infarcts / medullary or juxtacortical
Treatment
- opioid analgesia
- hydration
2. Anaemia
Sickled cells have shorter T½
3. Osteomyelitis
Bone crises difficult to distinguish from OM
- infarcted bone becomes infected
- Salmonella associated with sickle OM
Chambers et al J Paediatr Orthop 2000
- retrospective review of cases of OM / septic arthritis
- salmonella most common cause of OM
- temp > 38.2, WCC > 15 000
- bone scan and xray not helpful
- blood cultures and tissue biopsy most useful in diagnosis
4. Femoral head AVN
Incidence
- very common in homozygotes (30%)
Progression
Mont et al JBJS Am 2010
- systematic review
- asymptomatic medium to large lesions tend to progress (59%)
- small, medial lesions did not tend to progress (10%)
5. Humeral head AVN
Incidence
- homozygotes (50%)
Tourniquet
- avoid in homozygous
- beware in heterozygous
Perioperative Management
High risk of crisis peri-operative
- transfuse preoperatively to reduce percentage of HbS
- keep well hydrated and oxygenated
- avoid hypothermia
- avoid post operative anaemia
Core Decompression
Neumayr et al JBJS Am 2006
- RCT of core decompression v physio in stages I, II and III
- no evidence of improved outcome with core decompression at 3 years
THR
Hernigou et al Clin Orthop Rel Research 2008
- retrospective review 312 THR with average follow up 13 years
- average patient age 32 years
- 3% revision for infection
- 13% revison for aseptic loosening
- 25% incidence of peri-operative medial complications
Disease |
||||
Yes | No | |||
Test |
Positive | TP | FP | |
Negative | FN | TN | ||
The ability of a test to detect those with the index condition
- number with the condition
- true positives + false negatives
True positives / True positives + False negatives
Sensitivity = TP
TP + FN
Ability to exclude those without the index condition
- number without the condition
- true negatives + false positives
True negatives / True negatives + False Positives
Specificity= TN
TN + FP
The chance that the test result is correct
True positives + True negatives / total number of tests
Accuracy = TN + TP
TN + TP + FN + FP
The value of the negative test
NPV = TN
TN + FN
True negative / Total Number of negative tests
Positive Predictive Value= TP
TP +FP
The value of the positive test
- True positive / Total number of positive tests
Total number with disease at a certain time
Number of new cases within time period
Probability of an outcome in one group divided by the probability of that outcome in a second group
Group 1: Incidence 500 in 1 000 000 : 0.0005
Group 2: Incidence 100 in 1 000 000 : 0.0001
Relative risk = 0.0005/0.0001 = 5
Probability of a specific outcome
- 0 - 1
- may be expressed as a percentage
Calculated by subtracting the AR in the experimental group from the AR in the control group
- the absolute risk in the experimental group must be less than the control
Example A
Death | Survival | ||
New Treatment | 19 | 38 | 57 |
Old Treatment | 29 | 29 | 58 |
ARR = 29/58 - 19/57 = 17%
Example B
Drug reduces risk of MI by 25%
Normal mortality is 1%
ARR = 1/100 - 0.75/100 = 0.25/100 = 0.25%
Inverse of the Absolute Risk Reduction
Null hypothesis
- there is no difference between the two groups
Type 1 / Alpha error
- null hypothesis is true, but is rejected
- incorrectly rejects true null hypothesis
- false positive conclusion
- conclude treatment works when it does not
- set to 0.05 / 1 in 20 / p value of 0.05
Type 2 / Beta error
- null hypothesis is false, but is rejected
- incorrectly accepts a false null hypothesis
- false negative conclusion
- conclude that a treatment does not work, when it does
- typically set to 0.20 or 20% chance of false negative
- as power increased, probability of a type 2 error decreases
Power
- ability to test null hypothesis / probability of detecting a true positive difference
- increased by increasing sample size / improved design
- Power = 1 - beta
- usually set at 80%
- i.e. the study had a power of 80% to detect a certain difference in two groups
Level to set not purely by chance alone
P value / level of significance
- what is the chance that the null hypothesis is incorrect
- probability of a type 1 error
- generally p < 0.05 (less than 5% chance null hypothesis is incorrect)
- means low chance of type 2 error
- derived from the sample mean and the standard error
To calculate sample size you need:
- SD of the population (previous data, pilot data)
- confidence interval you want to accept (90,95,99)
- set the error (usually alpha =0.05)
Student t-test
- tests differences in population with normal distribution
- compares 2 continous variables
Chi square
- compares two or more discrete non continous variables
ANOVA
- analysis of variance
- compares one dependent variable amongst 3 or more groups simultaneously
MANOVA
- compares multiple dependent variables amongst 3 or more groups
Kaplan-Meier Curve
- used for estimating probability of surviving a unit time
- used to develop a survival curve when survival times are not exactly known
Multivariate analysis
- an analysis where the effects of many variables are considered
Hazard rate
- probability of an endpoint
- technical name for failure rate
Hazard ratio
- relative risk of an endpoint at any given time
Cox Proportional-Hazard Model
- multivariate analysis used to identify combination of factors predicting prognosis in a group of patients
- can test the effect of individual factors independantly
Level 1
Well designed randomised controlled trial
Systemic review of Level 1 RCT
Level 2
Lesser quality RCT
Prospective comparative study
- two groups
- no randomisation
Systemic review of Level 2 studies
Level 3
Case control
- two groups of similar patients
- one with treatment or disease of interest, one without
- look to see differences
Retrospective comparative
- two groups with different interventions
- not prospective
Level 4
Case series
Level 5
Expert opinion
1. Therapeutic Study
- investigates the result of a treatment
RCT
2. Prognostic Study
- investigating the effect of a patient characteristic on the outcome of a disease
Prospective cohort
3. Diagnostic Study
- investigating a diagnostic test
OA | Inflammatory / RA | Gout | Infection | |
WCC per mm3 | 2000 | < 75 000 | < 50 000 | > 80 000 |
% Neutrophils / PMN | < 25% | < 50% | > 75% | > 75% |
Viscosity | Normal | Variable | High | Low |
Glucose (percentage relative to serum) | Normal | Low | Normal | Low |
Other | Crystals |
Device that encircles a limb to occlude the vascular supply
Aim is to provide bloodless field
Local
- poor skin
- PVD
- DVT
- vascular bypass surgery
General
- sickle cell anaemia
- Polycythemia Rubra Vera
Pressure greatest at centre with parabolic fall off either side
Options
- tapered / conical
- non-tapered
1. Less for conical tourniquets than non conical
- limbs are not cylindrical
- limbs are tapered
- tourniquets should be too
- gives even pressure transmission
2. AOP reduced as tourniquet width increased
- Ratio Cuff Width to Limb Circumference
- < 0.1 : 1 then AOP > 400mmHg
- > 0. 3 : 1 then AOP < SBP
No clear guidelines
Aim just enough to stop arterial flow
Suggestions
- UL ~ 250mmHg (100mgHg over SBP)
- LL ~ 300 - 350mmHG (double SBP)
1. Nerve damage
- mainly secondary to pressure
- causes neuropraxia
- usually no Wallerian degeneration or loss of axoplasmic flow
- nerves very susceptible to excessive pressure (i.e. faulty gauge)
2. Muscle damage
- secondary to ischaemia
- damage maximum under cuff
3. Progressive acidosis in venous blood
- pH drops to 6.9 at 2 hours
- requires 15-20 minutes to return to prior levels
- patient's analgesia requirements will rise at this time
- have reaction to metabolites upon tourniquet release
4. Chemical burns
- cannot allow skin prep to pool under tourniquet
- becomes pressured into skin
- can create a 3o chemical burn
- place wool under to protect skin
- occlusive dressing over tourniquet to prevent pooling
- this complication is impossible to defend
Sapega et al JBJS Am 1988
- study in dogs
- limiting time to 1.5 hours minimised muscle ischaemia damage
- tourniquet release for 5 minutes
- permitted an additional 1.5 hours with comparative degree of safety
Generally
- tourniquet up for maximum of 2 hours
- release for minimum of 20 minutes