Miscellaneous

Arterial Supply Lower Limb

Femoral Artery

 

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

 

Profunda femoris

 

Angiogram Proximal Femur0001Angiogram Proximal Femur0002

 

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

 

Popliteal fossa

 

Boundaries

Superior: biceps laterally with semitendinosis / semimembranosus medially

Inferior: medial and lateral gastrocnemius

Floor: knee joint and capsule, popliteus

 

Popliteal artery

 

Popliteal arterty illustrationPosterior approach knee

 

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

 

Posterior Tibial 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

 

Peroneal Artery

 

Origin

- usually branch of posterior tibial

- 2.5 cm below popliteus

 

Relations

- runs along medial aspect fibula

- between FHL and T posterior

 

Anterior Tibial Artery

 

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

 

 

 

 

Arterial Supply Upper Limb

Subclavian Artery

 

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

 

Axillary Artery

 

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

 

Brachial Artery

 

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

 

Radial artery

 

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

 

Ulna artery

 

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

 

 

 

Blood Products

Goal

 

Ultimate goal of blood management is to AVOID allogenic blood transfusion

 

Problems

 

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

 

Transfusion Recommendations

 

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

 

Allogenic Blood Products

 

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

 

Transfusion Risk

 

METABOLIC

INFECTIVE

TRANSFUSION REACTION

Hypothermia

Viral – HIV. B. C.

Non Haemolytic

Hyperkalaemia

Bacterial

Haemolytic

Hypocalcaemia

Fungal

 

Pumonary oedema

Prion CJD

 

Coags/DIC/ARDS

 

 

 

1.  Non Haemolytic Transfusion Reactions

 

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

 

2.  Haemolytic Transfusion Reactions

 

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

 

3.  Metabolic

 

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

 

D.  Infective

 

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

 

Minimising Transfusion Requirement

           

Options

1.  Minimise intraoperative blood loss

2.  Cell saver

3.  Reinfusion drain

4.  Haemodilution

5.  Antifibrinolytics

6.  EPO

7.  Allogenic blood transfusion

 

1.  Minimizing Intraoperative Blood Loss

 

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

 

2.  Cell Saver

 

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

 

3.  Reinfusion Drain

 

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

 

4.  Haemodilution

 

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

 

5.  Antifibrinolytics

 

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%

 

6.  Recombinant human erythropoetin

 

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

 

7. Autologous Blood Donation

 

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%

 

Decision Making Jehova's Witness          

 

Issues

 

Doctor must act with a proper duty of care

Must act in patient's best interests

Really an informed consent issue

 

Scenarios

 

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 Grafts

Bone Healing

 

Bone healing requires 3 things

- osteoconduction - scaffold / matrix

- osteoinduction - growth factors

- osteogenesis - cells  to produce osteoid

 

Osteoconduction

 

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

 

Osteoinduction

 

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

 

Osteogenetic properties

 

Definition

- generation of bone from bone forming cells

- require presence of osteogenetic cells / osteoblasts

 

Substances

1.  Autograft

2.  Autologous bone marrow

 

Autograft

 

Sources

 

Cancellous

- iliac crest

- proximal tibia

- distal radius

- PSIS

 

Structural

- iliac crest

- fibular / vascularised graft

 

Properties

- osteoconduction

- osteoinductive

- osteogenic

 

Autologous Bone Marrow Aspirate

 

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

 

Allograft

 

Structural

 

Options

 

A.  Fresh

- inadequate time for disease screening

- HIV / HCV / HBV testing mandatory on donors

 

B.  Frozen

- stored at -60o

 

Allograft Talus Fresh Frozen

 

C.  Freeze-drying

- destroys all osteogenic cells

- limited osteoinductive properties

 

D.  Irradiated

- for sterility

- gamma irradiation (affects mechanical properties)

- ethylene oxide (affects osteoinductive properties)

 

Femoral Head Allograft 1Femoral Head Allograft 2

 

Properties

 

Osteoconductive

 

Types

 

Cortical strut grafts

- used in periprosthetic THR fractures

- creeping substitution via intra-membranous bone formation

 

Cortical Strut Grafts

 

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

 

2.  Demineralised Bone Matrix / DBM

 

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

 

Synthetic Grafts

 

Calcium Phosphate Synthetic Substitutes

 

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

 

Calcium Sulfate Synthetic Graft

 

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

 

BMP

 

Bone Morphogenic Protein

 

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

 

 

 

 

 

Bone Healing

Stages

 

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

 

 

 

CRPS

Definition

 

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

 

Historical Names

 

RSD (regional sympathetic dystrophy)

 

Sudeck's Atrophy 1900

- acute atrophy of bone associated CRPS

- associated with marked spotty osteoporosis

 

Aetiology

 

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

 

Pathology

 

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

 

Theories

 

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

 

Clinical Features

 

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

 

CRPS HandCRPS Hand 2

 

Stages

 

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

 

Prognosis

 

Mean duration of symptoms 32 months

 

Prevention

 

Zollinger et al Lancet 1990

- RCT of vitamin C 500mg v placebo post wrist fracture

- significant reduction in prevalence of CRPS 1

 

Management

 

Best results with early diagnosis and action

 

Physical Therapy

 

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

 

Medications

 

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

 

Sympathetic Interruption

 

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

 

Stellate Ganglion Block

 

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

 

Intravenous block / Bier's Block

 

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

 

Surgical Sympathectomy

 

Indication

- good but temporary relief from 4 blocks

 

Amputation

 

Contra-indicated

- poor results with stump RSD

 

Calcification

Background

Definition

 

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

 

Types

 

Dystrophic

Metastatic

 

Dystrophic

 

Chondrocalcinosis knee scopeKnee Chondrocalcinosis Xray

 

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

 

Metastatic

 

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 v Ossification

Xray

 

Calcification

- central pattern

- often increased opacity compared with bone

 

Ossification

- peripheral pattern

- similar density to bone

 

Tibial Myositis OssificansTHR Hetertropic Ossification

 

Histology

 

Calcification

- calcium salts only

 

Ossification

- osteoid matrix

Chondrocalcinosis

Definition

 

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

 

Differential Diagnosis

 

WHIP A DOG 

 

Wilson's

Haemochromatosis, hyperparathyroidism

Hypophosphatasia

Idiopathic

Pseudogout, pernicious anaemia

Amyloid, acromegaly

Diabetes

Ochronosis

Gout

 

Xray

 

Calcium in articular cartilage

- fine linear densities

- parallel to subchondral bone

 

Knee Chondrocalcinosis

 

Arthroscopy

 

Knee Arthroscopy Chondrocalcinosis

 

 

 

DDx Soft Tissue Calcification

DDx Soft tissue calcification

 

Hemangioma (commonest)

AV Malformation

Synovial sarcoma

Chondrosarcoma

MO / HO

Eptheloid sarcoma

TB calcified LN

 

 

 

 

 

Myositis Ossificans

Definition

 

Pathological bone formation in soft tissues

 

Epidemiology

 

In elbow

- 3% of trauma

- 89% if head injury + trauma

 

Types

 

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

 

Classification

 

1. Traumatic 

 

Most common

- deltoid

- quadriceps

- elbow joint

 

Ankle Interossesous MO following high ankle sprainElbow Myositis OssificansMyositis Ossificans Quadriceps

 

2. Non-traumatic

 

Adductor tendon in horse riders

 

Aetiology

 

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

 

Pathology

 

2° muscle inflammation & repair process abnormal

- extensive cellular infiltration

- collagen laid down

- collagen undergoes dystrophic calcification

- chondroblasts differentiate into osteoblasts 

- osteoid produced

 

Clinical Features

 

History of trauma

 

Initial pain / swelling / warmth

 

Develop hard mass

- slow resolution of pain

 

X-ray

 

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

 

Myositis Ossificans Tibia LateralTibial Myositis Ossificans AP

 

DDx 

 

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

 

Management

 

Prevention

 

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

 

Resection

 

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

 

Elbow MO PreoperativelyElbow MO Post resection

 

Myositis Ossificans Progressiva

 

Definition

 

Widespread ossification of connective tissue

 

Epidemiology

 

AD

 

Site

 

Spine

 

Major joints of upper limb

 

Histology

 

Poorly formed bone

Dense scar tissue

Islands of poorly formed cartilage

 

Clinical

 

Patients have short 1st metatarsal / metacarpal

 

Die of restrictive lung disease

 

 

 

 

Tumoural Calcinosis

Aetiology

 

Unknown

 

Epidemiology 

 

Rare

Black population

1st or 2nd decade

 

Presentation

 

Painless firm swellings over joints

- very common at large joints 

- hip and shoulder

 

Cosmetic & functional problem

- may ulcerate & discharge

 

Biochemistry

 

Calcium levels normal

Serum phosphate usually high

 

Management

 

Complete surgical excision

- recurrence common

 

 

 

 

 

Calcium

Hypercalcaemia

Definition

 

> 10 mg / dl

- must be corrected for albumin

 

Causes

 

Malignancy

- multiple myeloma / lung cancer / breast cancer

 

Hyperparathyroidism

- elevated PTH

 

Issue

 

High mortality associated with hypercalcaemia of malignancy

 

Physiology

 

40% albumin bound

50% ionised and active

 

Symptoms

 

Lethargy / confusion

- most commonly seen in malignancy

 

Kidney stones / abdominal pain / depression

- more likely seen in hyperparathyroidism

 

Management

 

Admit patient for medical management

 

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

 

 

Hypocalcaemia

Signs

 

Fall in level promotes tetanus

 

Chvostek sign

- tapping masseter muscle induces spasm

 

Trousseau Sign

-  flexion of thumb & wrist with extension of fingers

 

Carpopedal Spasm

 

ECG

 

Prolonged QT interval on ECG

 

Causes

 

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

 

 

 

Metabolism

Calcium

 

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

 

PTH

 

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

 

Vitamin D

 

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

 

CanMEDS

Definition

 

A framework of medical education for essential physician competencies

- aimed to improve patient care

- 7 essential roles

 

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

 

 

 

 

 

 

Coagulation Disorders

Background

Aim of Coagulation

 

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

 

Three phases

 

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

 

Platelets

 

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

 

Thrombolytics

 

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

 

 

Hemophilia

Definition

 

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

 

Haemophilia A

 

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)

 

Haemophilia B / Christmas Disease

 

FIX deficiency

 

Also X linked recessive

- less common

- 1:30 000

 

Similar spectrum of disease

- identical to haemophilia clinically

- treat with Factor IX cryoprecipitate

 

Pathogenesis

 

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

 

Clinical Features

 

Orthopaedic Manifestations

 

1.  Haematomas

2.  Haemarthrosis

3.  Bone cysts and pseudotumours

 

Depend on level of FVIII

 

<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)

 

1.  Haematomas

 

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

 

2.  Haemarthroses

 

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.  Bone cysts and Pseudotumors

 

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

 

Also

 

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

                            

Pathology

 

Haemarthrosis

- 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

 

Investigations

 

Platelet count / Bleeding time normal

APTT increased

PT Normal

Low factor VIII: C Activity

 

X-rays

 

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

 

Arnold Classification Arthropathy

 

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

 

DDx

 

Trauma

Juvenile onset RA

PVNS

Infection

Other coagulation disorder

 

Prognosis

 

Patients treated after 1985 can expect to have normal life spans

- older patients had high incidence of AIDS
- now recombinant

 

Management

 

Non Operative Management

 

Factor VIII

 

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

 

Acute Haemarthrosis

 

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

 

Subacute Haemophilia arthropathy

 

Treatment

 

1.  Prednisone 5 days

- 2-3 doses FVIII for level > 30%

- physiotherapy

 

2.  Prednisone 6 weeks                   

- FVIII > 20% 3 x week

- physiotherapy

 

Operative Management

 

Indications

- synovectomy

- contractures

- OA hip / knee / elbow / ankle

 

Perioperative Management

 

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

 

Synovectomy

 

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

 

Contractures

 

1.  Fixed ankle equinus

- T Achilles equinus

 

2.  FFD and valgus knee

- supracondylar osteotomy

 

Arthrodesis

 

AKJ / STJ

 

Knee Arthroplasty

 

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%

 

Hip Arthroplasty

 

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

 

Elbow

 

Chapman-Sheath et al JBJS Br

- TER in 7 elbows

- one deep infection

- excellent functional results at 4 year follow up

 

Other Disorders

Liver Disease

 

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

 

Vit K Deficiency

 

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

 

Antiphospholipid Syndrome

 

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

 

Thrombocytopaenia

 

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

 

 

 

Von Willebrand's Disease

Incidence

 

Most common of the bleeding disorders

- 1:100

 

Function

 

vWF            

- needed for platelet adhesion and platelet-platelet interactions

- also carrier for factor VIII / protects it from rapid breakdown

 

Aetiology

 

Gene on chromosome 12

1.  Reduced production VWF

2.  Increased proteolysis VWF

 

Leads to diminished platelet adherence at sites of vascular injury

 

3 types

 

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

 

Investigations

 

Bleeding times

- prolonged with normal platelet count

 

APTT

- slightly increased

 

vWF assay

- Ag based test

 

VIII:C

- decreased levels

 

Clinical

 

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

 

Management

 

Mild disease

 

Desmopressin / DDAVP

- stimulates release of vWF from endothelial cells

- useful only in type 1 / quantitative deficit

 

Surgery

 

Cryoprecipitate

- 1 bag / 10 kg bd

- several days after major operation

 

 

Consent

Definition

 

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

 

Involves

 

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

 

Guardianship

     

1.  Advanced Health Directive

2.  Relative or friend

3.  Legal Guardian

     

Age

 

No specific age limit

- need to be mentally competent

- i.e. 14 - 16 is old enough to sign own consent

 

Definition of Competency

 

Mini Mental State Exam

 

 

Crystal Arthropathies

Gout

DefinitionElbow Gout

 

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

 

Epidemiology

 

Adult men

- M:F = 20:1

- peak 40-60 years

 

Part of metabolic syndrome

- obese / HTN / high cholesterol / diabetes

 

Often have positive FHx

 

Physiology

 

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

 

Classification

 

A.  Overproducers ~ 10%

 

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

 

B.  Under-excretors ~ 90%

 

Secondary abnormal renal excretion of Uric acid

- diuretics

- CRF

 

Pathogenesis

 

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

 

NHx

 

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

 

Clinical presentation

 

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

 

Investigations

 

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

 

X-ray

 

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

 

Wrist Gout Severe

 

DDx 

 

Pseudo-gout

Septic arthritis

Acute bursitis

Cellulitis

RA

OA

Seronegative spondyloarthropathy

 

Management

 

Acute Gout

 

Medications

 

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

 

Prophylaxis

 

3 Tier Approach

 

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

 

Antihyperuricaemics

 

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

Hydroxyapatite Deposition

Types

 

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

 

Pathology

 

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

 

Clinical Features

 

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

 

Calcific TendonitisPellegrini Steida Lesion

 

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

 

Aspiration

 

Crystals too small to be seen with light microscopy

- hence will not see on aspiration

 

X-ray

 

Periarthritis seen as calcium in tendon

- especially rotator cuff

- chronic HA arthritis doesn't show on xray as well as CPPD

 

Management 

 

Non operative

 

Periarthritis

- RICE

- NSAID

- HCLA

 

Operative

 

Surgical removal

- calcific tendonitis

- problematic Pellegrini Steida

 

Chronic Arthritis

- treat as OA

- early arthroplasty if rapid bone destruction

 

 

 

 

Ochronosis

Definition

 

Degenerative arthropathy due to Alkaptonuria

 

Metabolics

 

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

 

Clinical

 

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

Chondrocalcinosis Knee ArthroscopyChondrocalcinosis Glenoid Arthroscopy

 

Definition

 

Pseudogout 

- Calcium Pyrophosphate Dihydrate (CPPD) crystals

- inflammatory arthritis of older individuals 

 

Chondrocalcinosis

- refers to any calcium in cartilage / menisci

 

Epidemiology 

 

M:F 2:1

 

Patient > 50

 

Sometimes familial

 

Association

 

DM

Hypothyroidism

Gout

Hyperparathyroidism

Haemochromatosis

Pernicious Anaemia

Onchronosis

 

Pathology

 

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

 

Clinical presentations

 

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

 

Synovial Fluid

 

CPPD crystals seen extracellular & in neutrophils

- rhomboidal

- weakly positively birefringent 

- IE Blue parallel to 1° order red filter & 135° to polarizer

 

X-ray

 

Chondrocalcinosis

 

Calcium in fibrocartilage & CT 

- punctate densities

- menisci / TFCC / pubis / annulus

 

Findings of OA usually present

 

Unusally joints

- PFJ

 

Screening Bloods

 

Ca / PTH

U&E

Serum Fe / Fe studies

TFT

Serum Alk Phos

 

Differential Diagnoses

 

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

 

Management

 

Options

 

1.  NSAIDS

2.  HCLA

3.  Colchicine

- 80% response 

4.  Joint washout

 

Joint washout

 

Don't debride / perform synovectomy

Worsens symptoms

 

Chondrocalcinosis KneeChondrocalcinosis Knee 2Chondrocalcinosis Knee 3

 

 

DIC

Definition

 

Disseminated Intravascular Coagulation

 

Pathology

 

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

 

Aetiology

 

Cancer: lung / pancreas / prostate

Obstetric: abruption / pre-eclampsia / amniotic fluid embolism

Severe trauma and burns

Gram negative sepsis

 

Clinical

 

Bleeding or thromboembolism

 

Bleeding

- more common secondary to thrombocytopaenia or coagulation factor depletion

- surgical sites

- skin / IV lines / venupuncture

- respiratory / urological / GIT

 

Diagnosis

 

Increased PT / APTT

 

Increased

- FDP / fibrin degradation products

 

Decreased

- fibrinogen

- platelets

 

Management

 

Principles

 

Control of underlying disorder

 

Bleeding

 

FFP / Cryoprecipitate

 

Clotting

 

Rarely a problem

- may get CVA or coronary artery thrombosis

- anticoagulate with Heparin

 

 

DVT / PE

Basic Science

Pathogenesis

 

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

 

Risk factors

 

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

 

Risk Groups

 

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

 

Rates without Prophylaxis

 

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%

 

Timing

 

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

 

Fatal PE & Theory of Propagation

 

Calf DVT

- calf DVT has 20% chance of propagation

- ? PE less likely

 

Proximal thrombi 

- are at greatest risk of embolism 

- 50% chance PE

 

Screening DVT 

 

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

 

Effect

 

PE leads to hypoxaemia from

- VQ mismatch 

- Right Heart Failure

 

Diagnosis DVT

 

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%

 

Diagnosis Pulmonary Embolus

 

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

 

Management

 

DVT / PE 

 

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

 

Prophylaxis

 

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

 

Preoperative

 

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

 

Intraoperative

 

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

 

Postoperative

 

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

 

Spinal surgery

 

FDA

- does not approve chemoprophylaxis for any spinal procedure

 

Epidurals

 

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

 

 

Chemoprophylaxis

Heparin

 

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

 

LMWH (Low Molecular Weight Heparin)

 

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

 

Oral Factor Xa inhibitors

 

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

 

Results

 

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)

 

Warfarin

 

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

 

Aspirin

 

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

 

IVC Filter

 

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

 

 

    

Mechanical Prophylaxis

Options

 

Early Mobilisation +

 

Compression Stockings

Pneumatic Compression Devices

Foot Pumps

 

1.  Graduated Compression Stockings

 

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%

 

2. Pneumatic Compression Devices

 

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%

 

3.  Foot pump

 

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

 

Infection

Infection Prevention

Background

Issues

 

Host

Wound

Operating room environment

Antibiotics

Operative technique

Post operative

 

Host

 

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)

 

Wound

 

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

 

Operating Room Environment

 

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

 

Antibiotics

 

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

 

Operative Technique

 

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

 

Post operative

 

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 Preparation

Goal

 

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

 

Types

 

Chlorhexidine

Iodine

Povidine - Iodine

Alcohol

 

1.  Chlorhexidine

 

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

 

2.  Iodine

 

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-

 

3.  Povidine- Iodine

 

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

 

4.  Alcohol

 

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

 

Results

 

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


Summary

 

 

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

 

 

Sterilisation

Definition

 

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

 

Techniques of Sterilisation

 

1. Wet heat

2. Dry heat

3. Chemical

4. Irradiation

 

1.  Wet Heat / Pressurized Steam

 

Autoclaving

- most reliable

- metal instruments

- glass

- some plastics, fabrics & rubbers

 

Technique

- 121°   >103 kPa  ~ 15 minutes

 

Flash

- 134°  205kPa  3 minutes

 

2.  Dry Heat

 

Uses

- glassware

- oils & fats

 

Technique

- fan-driven oven

- 160° C

- minimum 2 hours

 

3.  Chemical

 

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

 

4.  Radiation / Sterrad

 

Hydrogen Peroxide made to release free radical by radiowave - 45° C

 

Summary

 

    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    

 

 

 

 

 

 

 

 

Microbes & Antibiotics

Antibiotics

Antibiotic Properties

 

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

 

Method of Action

 

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

 

1.  Penicillins

 

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

 

Cephalosporins

 

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

 

Aminoglycosides

 

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

 

Ciprofloxacin

 

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

 

Vancomycin

 

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

 

 

 

Microbes - General

Gram Positive

 

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

 

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

 

Cell Structure

 

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

 

Staining

 

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

 

Antimicrobial Actions

 

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

 

Antibiotic Resistance

 

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

 

 

Microbes - Specific

Staphylococci

 

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 

 

Streptococci

 

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

 

Gram negative Enteric Bacteria

 

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

 

Haemophilus

 

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

 

Neisseria

 

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

 

 

Osteomyelitis

Acute

Definition

 

Infection of bone 2° blood-borne bacteria

 

Epidemiology

 

Most common children

- peak 10 years

 

True haematogenous OM rare in adults

- usually involves spine

 

M: F 2:1

 

Site

 

Most common femur & tibia

- initially affects metaphysis 

- distal femur

- proximal and distal tibia

 

Pathogenesis

 

1.  Infants

 

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

 

2.  Children

 

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

 

3.  Adults

 

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

 

Aetiology

 

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

 

Clinical Features

 

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

 

Bloods

 

ESR / CRP raised

WCC may be increased

 

Early blood culture before antibiotics

 

X-ray 

 

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

 

Proximal Femur Osteomyelitis

 

Bone Scan

 

Positive all 3 phases in 24 - 72 hours

- sensitivity & specificity 90%

 

US

 

Identify fluid in joint space which may be septic arthritis

 

CT

 

Sequestrum

 

MRI

 

Increased signal on TI

 

Abscess

- high signal rim with low signal in middle

- rim / ring enhancement with gadolinium

 

Proximal Femur Osteomyelitis MRIProximal Femur Osteomyelitis MRi 2

 

Aspiration / Biopsy

 

Subperiosteal / intra-osseous

- positive culture in 60 - 90%

 

Management

 

Principles

 

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

 

Antibiotics

 

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

 

Surgery

 

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

 

Complications

 

Septic arthritis

- < 12/12 old (blood vessels cross physis)

- intra-articular metaphysis i.e. hip

 

Septicaemia

 

Premature physeal arrest

 

Pathological fracture

 

Chronic OM

 

Prognosis

 

Recurrence 4%

 

Chronic

Management PrinciplesFemoral Osteomyelitis

 

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

 

Aetiology

 

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

 

Cierny Classification

 

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

 

Pathology

 

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

 

Complications

 

Pathological fracture

- 2° bone destruction & brittleness

 

Malignant transformation ~ 1%

- sarcoma

- sinus epithelioid ca

 

Clinical Features

 

Recurrent flares

- pain & fever

- redness / tenderness

 

Discharging sinus

 

X-ray

 

Variable amounts of

- patchy lysis with surrounding sclerosis

- ± dense sequestrum

- bone can be deformed

 

Chronic Osteomyelitis Femur APChronic Osteomyelitis Femur Lateral

 

Bone Scan

 

Increased uptake in lesion

 

CT scan

 

Shows bony architecture

 

Extent of bone destruction

- sequestra

- abscess cavities

 

MRI

 

Best to define extent of infection

 

Chronic Ostetomyelitis Femur MRI CoronalChronic Ostetomyelitis Femur MRI Axial

 

Bloods

 

Variable increase ESR & WCC with flares

Repeat MCS / sensitivity changes

 

Management 

 

Concept Type A / B Host

 

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

 

1.  Host Factors

 

Most important in outcome

- control diabetes

- maximise nutrition

- cease smoking

 

2.  Identify organism

 

M/C/S

 

Microbiology

- most common S aureus ~ 40 %

- 25 % mixed

- Gram negative 35 %

 

3.  Debridement

 

Removal of all dead bone

Treat infection like tumour

- meticulous debridement of necrotic tissue

 

4.  Stabilise

 

Infected non union worst outcome

 

External fixation / Ilizarov excellent management

- gives stability

- eliminates metal at osteomyelitis site

- obtains union

- deals with bone defect

 

Ilizarov Frame

 

5.  Dead Space

 

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

 

6.  Skin Cover

 

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

 

7.  Eradicate infection

 

IV Antibiotics

Repeated debridement

 

8.  Address bony defect

 

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

 

Type C patients

 

1.  Dress sinus / drain acute abscess / suppressive Abx 

 

2.  Consider amputation

 

 

Septic Arthritis

Definition

 

Joint inflammation secondary pyogenic organism

 

Epidemiology

 

All age groups

 

Usually children

- 50% < age 3

 

M= F

 

Any joint

- Infants = Hip

- Children = Knee

- Adults = Large Joints

 

IVDU - SCJ & SIJ

 

Pathogenesis

 

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

 

Predisposition

 

Host

- immunodeficiencies

 

Joint

- previous joint trauma

- RA

- previous HCLA

 

Bacteraemia

 

Aetiology

 

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

 

Pathology

 

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

 

Clinical Features

 

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

 

Bloods

 

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%

 

Aspiration

 

Indications

- knee / ankle

- shoulder / elbow

- ASAP

 

Contra-indications

- neonate hip

- aspiration difficult & need GA

- drain ASAP

 

MCS & Cell count

 

WCC > 50 000 per ml

Neutrophils > 75%

 

Gram stain Positve 30%

Culture positive 60%

 

X-ray

 

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

 

Te Scan 

 

DDx focal metaphyseal OM 

Identify AVN femoral head

 

US

 

100% sensitive at detecting fluid in joint

- useful to diagnose hip effusion

 

MRI

 

DDx

- OM

- psoas abscess

 

Diagnosis

 

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

 

DDX

 

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

 

Management

 

1.  Surgical Drainage

 

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

 

2.  Antibiotics

 

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

 

Complications

 

Joint destruction - ankylosis / OA

 

Neonate Hips 

- dislocation / subluxation

- destroyed epiphysis - Growth disturbance / LLD / coxa vara / breva

- absence of head / AVN

- pseudoarthrosis of femoral neck

 

Hip Septic Arthritis

 

 

 

 

Synovial Fluid Analysis

Cell Counts x 106/L

 

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

 

Different Units

 

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

 

Cell Differential

 

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

 

Additional

 

Glucose < BSL

 

± Crystals as acid Ph decreases solubility

- presence of crystals does not exclude infection

 

Gram stain positive 30%

Culture positive 60%

 

Weinstein

 

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

 

 

 

Unusual Infections

Chronic Relapsing Multifocal Osteomyelitis

CRMO

 

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

 

Criteria

 

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

 

Haematological Examination

 

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

 

Management

 

NSAIDs 

Steroids may be of some benefit

Interferon used in severe cases

 

Prognosis 

 

Usually protracted course

Usually self limited

 

Differential

 

Viral polyarthritis

Juvenile chronic arthritis

Acute osteomyelitis

Neoplasia

- Neuroblastoma

- Leukaemia

- Rhabdomyosarcoma

Langerhans cell histiocytosis

 

Garre's Primary Sclerosing Osteomyelitis

 

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

 

 

 

Fungal Infection

Blastomycosis

 

From lung portal

 

Affects

- Epiphyses and metaphysis long bones

- also hands and feet

 

Amphotericin

 

Coccidiomycosis

 

As above

 

Cryptococcosis

 

In immunocompromised

- HIV, Leukemia/lymphoma, DM

 

Produce radiolucent lesions with no periosteal reaction

 

Amphotericin B

 

 

 

 

 

Gas Gangrene

Definition

 

Clostridial Myonecrosis

- necrotizing, gas producing infection of skeletal muscle 2° Clostridia

- life threatening & rapidly progressive

 

Classification

 

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

 

Epidemiology

 

Open Fractures

Penetrating wounds

War & Farmyard wounds

Surgical wounds - Bowel / Poor technique

Hypovascular limbs - DM / PVD

 

USA 1000 / year 

- 0.05% of open fractures

 

Pathology

 

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

 

Clostridium perfringens

 

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 

 

Pathology

 

Necrotic muscle

- reddish purple & friable

- becomes greenish purple

- gas in tissue

 

Clinical Features

 

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 

 

Investigations

 

Clinical diagnosis

- positive blood culture in 15%

- gram-stain of exudate not helpful

- positive Nagler's test (Lecithinase turns egg yolk opaque in agar)

 

X-ray

 

Gaseous distension of muscle & fascial planes

 

DDx

 

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

 

Prophylaxis

 

Awareness 

- early meticulous debridement

- leave wound open

 

Appropriate antibiotics

- Kefazol

- + Gentamicin if extensive contamination

- + Penicillin if farmyard 

 

Management

 

1. Surgery

 

Most important 

- Delay = Death

 

Emergency exploration

- examine muscles directly

- differentiate Myonecrosis from Anaerobic cellulitis from Necrotising Fasciitis

 

Appropriate debridement

- radical myoexcision

- fasciotomies

- ± amputation

 

2. Antibiotics

 

Penicillin high dose

- allergies - clindamycin

- beware penicillin resistance

- gentamycin for co-infection

 

High dose clindamycin

- may block Clostridial exotoxin

 

3.  Resuscitate

 

Fluid loss +++

- prompt replacement 

- monitor fluid balance 

 

4. Hyperbaric O2

 

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

 

Prognosis

 

Mortality 

- WWI = 50% 

- WWII = 25%

 

Now lower

- 50% if reaches trunk

 

Hyperbaric Oxygen

Mechanism

 

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

 

Indications

 

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

 

Technique

 

Usually use 2-2.8 Atmospheres

 

Need 6/52 to gain vascular ingrowth

 

Leprosy

 

Definition

 

Chronic granulomatous infection of skin & peripheral nerves by Mycobacterium Leprae

 

Epidemiology

 

Endemic in some tropical regions

Commonest cause of peripheral neuropathy worldwide

 

Microbiology

 

Acid-Fast bacilli

- Carbol Fuchsin stain

- unable to be grown on artificial media

 

Pathology

 

Virchow Cells

Vacuolated macrophages

Granuloma

 

Transmission

 

Definitive route of transmission has not been proven

- is likely to be respiratory similar to TB

- broken skin transmission reported

 

Clinical Findings

 

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

 

Types

 

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

 

Diagnosis

 

Bacilli seen in scrapings from skin or nasal mucosa

Culture Negative

 

Management

 

Sulphone & Rifampicin for ~ 2yrs

 

 

Necrotising Fasciitis

Definition

 

Infection of skin and subcutaneous tissue

- spreads across fascial planes

- many microbes can be responsible

 

Types

 

Type 1 Polymicrobial

 

Type 2 Monomicrobial

 

Aetiology

 

Group A Beta Hemolytic Strep (S. pyogenes)

- most common cause monomicrobial

 

S. Aureus / MRSA

 

Vibrio

- wound contaminated with saltwater

 

Clostridium

 

Anaerobes

 

Predisposing factors

 

Trauma

- insect bite

- skin laceration

- needle injection

- IVDU

 

Post operative

 

Diabetes

 

Clinical

 

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

 

MRI

 

Can distinguish between cellulitis and necrotising fasciitis

- increased T2 signal along fascia

 

Management

 

High index clinical suspicion

 

Surgery

 

Debridement of infected skin and subcutaneous tissue

- tissue and fluid sent for immediate MCS

- exclude myonecrosis

 

Antibiotics

 

Broad spectrum

- penicillin / vancomycin

 

Hyperbaric Oxygen

 

Skin cover

- becomes late problem

- patient may need extensive skin flaps

 

Prognosis

 

Mortality rates up to 25%

 

 

SAPHO

Definition

 

Clinical syndrome characterised by

 

Synovitis

Acne

Pustulosis

Hyperostosis

Osteitis

 

Aetiology

 

Unknown

- high prevalence of HLA B-27 antigen

- similarities to seronegative spondyloarthropathy 

 

Four types

 

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

 

Symptoms

 

Sternoclavicular hyperostosis

Sterile inflammatory lesions

Hyperostosis & osteitic lesions may be similar to malignant conditions

Synovitis does not usually lead to bony erosions

 

Management

 

Analgesics & oral anti-inflammatories

 

Prognosis

 

Favourable

- often protracted course with intermittent relapses & remissions without serious disability

 

 

Syphillis

Organism

 

Treponema Pallidum

 

Spirochete transmitted via

- direct contact with denuded epithelium

- transplacental infection

 

Types

 

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

 

DDx

 

Abuse

CRMO

Leukaemia

CMV

Rubella

Rickets

 

Investigation

 

Bone Biopsy

- spirochaetes

 

RPR Rapid Plasma Reagin

- screening

 

Fluoroscent Treponemal Antibody Test 

- confirmation

 

Lumbar puncture

- neuro-syphilis

 

Management

 

Antibiotics

 

Penicillin

- no reported resistance

- 100000 U/kg/D tds for 2/52

 

Syphilus of the bones

 

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

 

 

 

 

 

TB

Definition

 

Caseating granulomatous mycobacterium infection 

 

Epidemiology

 

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

 

Sites

 

10% extrapulmonary

 

1% of skeletal

- half in spine

- mono-articular arthritis

 

Microbiology

 

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

 

Pathogenesis

 

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

 

Pathology

 

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

 

Clinical Features

 

Initial infection usually asymptomatic

- slight malaise / fever

- lymphadenopathy

- pleurisy

 

Variable symptoms 2° TB

- fevers with night-sweats

- malaise 

- weight loss

- cough / haemoptysis

 

CXR

 

Apical lesion 

Multinodular infiltration with cavitation

 

Microbiology

 

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%

 

Tuberculin Skin Test

 

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

 

Management

 

Antibiotics

 

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

 

Joint Infection

 

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

 

TB Spine /  Pott's Disease

 

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

 

 

 

Tetanus

 

Definition

 

Acute disease

- characterised by generalized rigidity & convulsions

- caused by exotoxins/neurotoxins produced in Clostridia Tetani infections

 

Epidemiology

 

Annual world mortality is 1 million

 

West 15-100/year

 

Aetiology / Pathology

 

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

 

Tetanus-Prone Wound

 

Open fractures

Puncture >1cm

Foreign Body

Contamination / Tissue damage

Bite

Ischaemic / denervated tissue

Crush / burn / frostbite

 

Prophylaxis 

 

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

 

Clinical

 

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

 

Prognosis

 

60 % die in 2/52

- spasms disappear by 1-3 /52

- if survive, recover by 6 /52

- respiratory compromise is major cause of death

 

Investigations

 

No specific tests

 

C. Tetani cultured in one third of wounds

 

Management Tetanus

 

1.  Wound care

- debride necrotic & contaminated tissue

 

2.  Penicillin G

- tetanus spores destroyed by AB

- vegetative form sensitive to AB

- 2 Million units q6h for 10/7

 

3.  Antitoxin

- a more concentrated TIG for treating clinical tetanus

- neutralises circulating toxin

- doesn't affect toxins already fixed in CNS

 

4.  Other

 

Spasms control

Quiet dark room

Diazepam

Consider thiopental infusion

Care of airway (may need ventolation)

Hydration & nutrition

 

 

 

Viral

HIV

Epidemiology

 

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 %

 

Aetiology

 

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

 

Microbiology

 

Retrovirus

- reverses RNA of virus into DNA

- incorporates into cell DNA

- uses reverse transcriptase

 

Pathology

 

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

 

Clinical Features

 

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

 

Stages

 

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

 

Diagnosis

 

Window period

- usually 2-6/52

- > 6/12 considered safe

 

ELISA

- sensitive, but not specific

 

Western Blot Test

- specific

 

Complications

 

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

 

Surgery

 

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

 

Hepatitis B & C

Hepatits C

 

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

 

Hepatitis B

 

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

 

 

 

 

Inflammatory Arthritis

Immunity

Definition

 

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

 

Development

 

Lymphocyte precursors come from bone marrow

- migrate to modifying organ

- then return to nodes & bone marrow

 

T Cells

 

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

 

B Cells

 

Cells that populate spleen & liver

 

Mediate Humeral Immunity

 

B lymphocytes differentiate into

- pasma cells

- memory B cells

 

Humoral Immunity

 

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

 

Major Histocompatibility Complex

 

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

 

Complement System

 

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

 

Cellular Immunity

 

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

Inflammation

Definition 

 

Response of body to injury

 

Process

 

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

 

Inflammatory Cells

 

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

 

Mediators

 

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

 

Vasoactive Amines

 

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

 

Prostaglandins

 

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

 

Growth Factors / Cytokines

 

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

 

Interferons

 

Interferon Gamma

- produced by activated T cells

- induces expression of Type II MHC antigens

- activates macrophages for antigen presentation

 

Neutral Proteinases

 

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

 

 

 

Polymyositis & Others

Polymyositis 

 

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

 

Dermatomyositis

 

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%

 

Polymyalgia Rheumatica

 

Epidemiology

 

Middle aged women

 

Symptoms

 

Tender pectoral & pelvic muscles

 

Risk Temporal Arteritis

 

Investigations

 

ESR high

 

Management

 

Rapid response low dose steroids

 

Postinfectious Arthritis

 

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

 

Sarcoidosis

 

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

 

Scleroderma

 

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

 

 

 

 

Rheumatoid Arthritis

Definition 

 

A chronic systemic, autoimmune inflammatory disease of unknown cause

 

Epidemiology

 

1% of population

 

M:F = 1:3

 

Peak onset 40 years

 

Most common inflammatory arthropathy

 

Aetiology

 

Autoimmune

- trigger not identified

- cell mediated immune response

 

Combination of

1.  External trigger ? Infection

2.  Genetic susceptibility

 

Pathogenesis

 

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

 

Rheumatoid Factor

 

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

 

Pathology

 

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

 

Clinical

 

Most commonly present with

- malaise

- fever 

- fatigue

 

Symmetrical pain & swelling in hands, wrists & feet

 

Four Presentations

 

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

 

Four Outcomes

 

Short - Lived & No disability 25%

 

Mild Disability 25% 

 

Progressive 40% 

- variable progressive deformity

 

Severe 10% 

- gross deformity / severe disability / rapid progression

 

Symptoms

 

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

 

Felty's Syndrome

 

Combination RA / Splenomegaly / Neutropenia

 

Other features are

- lymphadenopathy

- skin pigmentation

- chronic leg ulceration

- thrombocytopaenia

- haemolytic anaemia

 

Sjogren's Syndrome

 

Combination of

- dry eyes / keratoconjunctivitis sicca

- dry mouth / xerostomia

- connective tissue disorder - RA in 50%

 

Histology

 

Synovial Biopsy

- non specific chronic inflammation

 

DDx

 

Seronegative Spondyloarthropathies (Reiters / AS / Psoriasis / Enterocolitis)

Crystal Arthropathies (Gout / CPPD / HADD)

CT Diseases (JRA / SLE)

Polymyalgia Rheumatica

Sarcoidosis

 

Dx Crtieria 1987 Am College of Rheumatology 

 

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

 

Medical Management

 

1.  Symptom Modifying Drugs

 

NSAID

 

First-line therapy

- alleviates pain & swelling

 

Side Effects 

- troublesome

- skin rashes / gastric ulceration / renal dysfunction

 

2.  Disease Modifying drugs (DMARDs)

 

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

 

3.  Corticosteroids

 

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 

 

4.  Biological Agents / Immune Modulators

 

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

 

 

Spondyloarthropathy

Diseases

 

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

 

Reiter's Disease

 

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

 

Inflammatory Arthritis Knee

 

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%

 

Psoriatic arthritis

 

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

 

Enteropathic arthritis

 

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 Lupus Erythematosus (SLE)

Definition

 

Systemic Connective Tissue Disease

 

Chronic inflammatory disease resulting from abnormal immunoregulation

 

Aetiology

 

Unknown

 

Thought similar to RA

1.  Genetic factors

2.  Environmental factors

 

Epidemiology

 

Young females

 

F:M 9:1

 

Peak 35 years old

 

Geographic variations

- more common in black and asian populations

 

Clinical Features

 

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

 

DDx RA

 

1. No ankylosis or contractures

2. No erosive changes on xray

3. Less destructive than RA

 

Investigations

 

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

 

Management

 

Medical

 

Avoid sunlight as it exacerbates symptoms

 

Options

 

NSAIDS

Steroids

Cyclophosphamide

DMARDS

Anti-immune as per RA

IV immunoglobulin

        

Arthroplasty

 

Higher risk of deep infection

 

Needlestick

Seroconversion

 

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%

 

Contamination

 

Sharp injury in 1.3 - 15.4% of operations

- half from suture needle

 

Mucous membrane contamination

- facial 100% in THR

- risk unknown

 

Management of Needlestick

 

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

 

Reduction of Exposure

 

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

 

 

 

 

 

 

Non Operative Management

ELMPOPI

 

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

Definition

 

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

 

Fracture Healing

 

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

 

Bone Healing

 

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

 

Mechanobiology of Skeletal Regeneration

 

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

 

Concept Interfragmentary Strain

 

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

 

Aetiological factors

 

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 

 

Classification Non-union

 

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

 

Management

 

Options

 

1.  Rigid stabilization

 

2.  Autograft / allograft

 

3.  Other modalities

- Electrical stimulation

- US therapy

- BMP 

- Bone marrow aspirate

 

Electrical Stimulation

 

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

 

Pulsed US 

 

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 

 

BMP

 

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

 

Bone Marrow Aspirate

 

Results

 

Hernigou et al JBJS Am 2006

- 20mls BMA injected percutaneously into 60 atrophic tibial non unions

- union obtained in 53 cases

 

 

OA

Definition

 

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

 

Classification

 

Primary 

 

Idiopathic

- cartilage degenerates in all as time goes by

- high incidence of cartilage wear & OA in 7th decade

 

Secondary

 

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

 

Epidemiology

 

Prevalence

- rises steeply with age

- 15% at 40

- 75% at 70 

- > 50% have symptoms

 

Cause

 

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

 

Pathology

 

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

 

Patterns

 

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

 

 

Osteoporosis

Epidemiology

 

1/3 caucasian women > 64

 

Risk Factors

 

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

 

Primary

 

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

 

Secondary

 

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

 

DEXA Screening

 

DEXA ScanBMD Hip 2

 

BMD Spine

 

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

 

Investigation

 

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

 

Issues

 

Wrist fractures

Hip fractures

Vertebral fractures

Sacral insufficiency fractures

 

Sacral Insufficiency Fracture

 

Management

 

Premenopausal

 

Adequate calcium and vit D

Adequate weight

Exercise

No smoking

 

Post menopausal

 

Calcium Carbonate

 

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

 

Vitamin 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

 

Estrogen

 

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

 

Calcitonin

 

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

 

Bisphosphonates

 

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

 

Bisphosphonate Cortical ThickeningBisphosphonate Cortical Thickening 2

 

Bisphosphonates Femoral insufficiency fractureBisphosphonate Femoral Fracture

 

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

 

Exercise

Paget's Disease

Definition

 

Chronic, non metabolic bone disorder

Characterised by increased bone resorption, bone formation and remodelling

 

Epidemiology

 

Rare < 40

1 – 3 % population over 60

M > F

 

Aetiology

 

Unknown

 

Paramyxovirus implicated

- measles

- RSV

- canine distemper virus

 

Electron Microscope

- viral like inclusion bodies in osteoclasts

 

No presence of specific viral antibodies

 

Pathophysiology

 

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

 

Types

 

Monostotic 25%

Polyostotic 75%

 

Sites

 

Pelvis

 

Pagets Hemipelvis

 

Lumbosacral spine

 

Femur

 

Paget's Femur 1Paget Femur 2

 

Tibia

 

Pagets Tibia

 

Presentation

 

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

 

X-ray

 

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

 

Pagets Hip

 

Deformity

- sabre tibia

- coxa vara / protrusio hip

- skull (leonine)

 

Pagets TibiaPagets Disease Tibia Femur

 

Bone scan

 

Shows increased uptake

 

Pagets Bone Scan

 

Biochemistry

 

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

 

Histology

 

Rarely needed

Predisposes to fracture

Mosaic pattern of poorly organised lamellar bone

Mulitnucleated osteoclasts

 

Management

 

Non operative Management

 

Bisphosphonate

 

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

 

Operative Management

 

Hip pain

 

DDx

- fracture (tension side)

- bone pain (treat with bisphosphonates)

- hip OA (confirm with intra-articular HCLA)

- tumour

 

THA

 

THR Pagets 1THR Paget's 2

 

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

 

TKA

 

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

Definition

 

Platelet rich plasma

 

Concept

 

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

 

Technique

 

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

 

PRP 1

 

Centrifuge for 15 minutes

 

PRP MachinePRP 2

 

PRP

- draw off plasma

- take PRP

 

PRP 3PRP 4PRP 5

 

Thrombin

- remove from small tube

 

PRP 6PRP 7

 

Use premade injection device as required

 

PRP 8

 

Possible Indications

 

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

 

Rotator Cuff Repair PRP 1Rotator Cuff Repair PRP 2PRP Clot

 

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

 

Sickle Cell Disease

Epidemiology

 

Black population

- heterozygote protective from malaria

- AD

 

Pathogenesis

 

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

 

NHx

 

High risk of pneumococcal septicaemic and meningitis

 

Clinical

 

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%)

 

Operative Management

 

Issues

 

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

 

Femoral Head AVN

 

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

 

 

 

 

Statistics

 

   

Disease

   
    Yes No  

Test

Positive TP FP  
  Negative FN TN  
         

 

Sensitivity

 

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    


Specificity

 

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

 

Accuracy

 

The chance that the test result is correct

 

True positives + True negatives / total number of tests

 

Accuracy =                TN + TP    

                        TN + TP + FN + FP

 

Negative Predictive Value / NPV

 

The value of the negative test

 

NPV =            TN

                    TN + FN                

 

True negative / Total Number of negative tests

 

Positive Predictive Value / PPV

 

Positive Predictive Value=            TP

                                                TP +FP

 

The value of the positive test

- True positive / Total number of positive tests

           

Prevalence

 

Total number with disease at a certain time

 

Incidence

 

Number of new cases within time period

 

Relative Risk

 

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

 

Absolute Risk

 

Probability of a specific outcome

- 0 - 1

- may be expressed as a percentage

 

Absolute Risk Reduction

 

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%

 

Number Needed to Treat

 

Inverse of the Absolute Risk Reduction

 

Error Types

 

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

 

Confidence

 

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

 

Sample Size

 

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)

 

Statistical Tests

 

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

 

Levels of Evidence

 

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

 

Types of Studies

 

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

 

 

Synovial Fluid Analysis

 

 

  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
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Tourniquet

DefinitionTourniquet Arm

 

Device that encircles a limb to occlude the vascular supply

 

Aim is to provide bloodless field

 

Contra-Indications

 

Local

- poor skin

- PVD

- DVT

- vascular bypass surgery

 

General

- sickle cell anaemia

- Polycythemia Rubra Vera

 

Cuff Design

 

Pressure greatest at centre with parabolic fall off either side

 

Options

- tapered / conical

- non-tapered

 

Arterial Occlusion Pressure

 

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

 

Cuff Pressure

 

No clear guidelines

 

Aim just enough to stop arterial flow

 

Suggestions

- UL ~ 250mmHg  (100mgHg over SBP)          

- LL ~ 300 - 350mmHG  (double SBP)

 

Mechanism of Tourniquet Injury

 

Thigh Tourniquet

 

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

 

Cuff Times

               

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