The Spectrum Of Arthritis

15.1.07

What is arthritis?
• Damage to joints.
• Pain (usually).
• Reduced function - "joint failure."
• Many causes.
• Various treatments - including curative!

Spectrum of arthritis
• Aches and pain very common.
• Not all pains are "arthritis."
• Hundreds of different types of arthritis.
• Average doctor: poor/no training in musculoskeletal disease.
• Importance of early diagnosis (modifiable disease).
• Massive market - pharmaceutical industry!
• One, few or many joints affected.
• Not only joints affected!
• Many different aetiologies.

How to diagnose arthritis
• History.
• Examination.
• Blood tests:
-ESR.
-CRP.
• Imaging:
-X-ray.
-MRI.
-Ultrasound.
-Nuclear medicine.

Aetiology of rheumatic diseases
• Almost all have complex multifactorial aetiology.
• Multiple genes.

Clinical problems
• Single joint (monoarthritis).
• Many joints (polyarthritis).
• A few joints (oligoarthritis).

Aetiology
• Infective (septic).
• Degenerative (osteoarthritis).
• Metabolic (gout).
• Inflammatory (rheumatoid arthritis).

Monoarthritis
• Septic arthritis - can be sexually transmitted.
• Osteoarthritis.
• Crystalarthritis.

Septic arthritis
• Medical emergency.
• Curable.
• Antibiotics IV.
• Lose joint (and limb) if too slow.

Gout
• Podagra.
• Pain "exquisite."
• High serum urate.
• Crystals in joints.
• Profound inflammation.
• Chronic:
-Trophic.
-Renal disease.

Gout: diagnosis
• Serum urate.
• Direct examination for crystals.
• Look at underlying causes.

Pyarthrosis
• Sepsis.
• Crystal synovitis.
• Rheumatoid arthritis (and other inflammation).

Oligoarthritis
• Reactive (HLA-B27-related) arthritis.
• [Psoriatic arthritis.]
• Osteoarthritis.

Reactive arthritis
• As consequence of infection.
• Joint pain.
• Eye problems.
• Ulceration.

Ankylosing spondylitis
• More common in men than women (4-9:1).
• Inflammation in sacroiliac joint, spreading up back.

Psoriatic arthritis
• As result of psoriasis.
• Can be one of worst forms.

Osteoarthritis
• Joint "wearing" inevitable with time.
• When is "wear" "disease"?
• Various patterns: one/many joints.
• Surgery ultimate therapy.
• Lifestyle modification.
• Simple analgesia.
• Disease modification…?

Degenerative disease
• Cardinal features of arthritis on x-ray:
-Joint space narrowing.
-Osteophytes.

Rheumatoid arthritis
• Most common autoimmune disease.
• Not just joints.
• High morbidity.
• High mortality.
• Symmetrical small joint polyarthritis (only synovial).
• Inflammatory.

Module 2.08

Pain Taking Over.
15.1.07 - 26.1.07.

Normal And Abnormal Functional Anatomy Of The Lower Limb

12.1.07

"Lower limb problems are the most commonly dealt with by physicians."

Physical stress - hip joint
• Trabecular structure of proximal femur generally well-adapted to cope with angle of inclination (normally ~1250 in adult) and bending moments it causes medially.
• However, significant deviations (coxa vara, coxa valga) can lead to reduced mobility and/or fractures of femoral neck.

Iliofemoral ligament prevents hyperextension of hip - strongest ligament in body.

Fracture of neck of femur
• Displacement of distal bone fragment caused by pull of powerful muscles.
• Note in particular: external rotation of leg with foot characteristically pointing laterally.
• Particularly in elderly women, mainly due to thinning of cortical and trabecular bone.
• Avascular necrosis of femoral head is a common complication.

Knee joint
• Articular surface involved in main movement of knee: flexion and extension.
• Articular surfaces of femur represent segment of pulley.
• Cruciate ligaments appear crossed in space.
• Situation important to remember during normal knee movement - also involves some gliding and rotation.
• Cruciate ligaments represented by crossed 4-bar linkage.
• Together with medial and collateral ligaments, intersect at same crossing point - can be maintained in extension and flexion.
• Note: extension in femoral condyles has much greater contact areas as in flexion thus significantly reducing pressure.
• Various structures (e.g. ligaments, menisci and tendons) help stabilise knee joint and dissipate pressure.

The Grandmother's Fall CPC

8.1.07

Vitamin D
• Sources:
-From 7-dehydrocholesterol in skin.
§Up to 80% requirements → D3.
-From diet (D2).
§Fish, plants etc.
§Fortified.
• Metabolism:
-Converted to 25(OH)D in liver.
-Then to 1,25(OH)2D in kidney.
-Renal feedback control of 1,25 form to maintain both:
§Itself.
§Ca2+ and PO43- levels.
• Functions:
-More like steroid hormone:
§Absorption of calcium and phosphorus.
§If Ca2+ low, works with parathyroid hormone to increase release.
§Normally required for mineralisation of bones.
§Renal resorption of Ca2+ (?exact mechanism).
§? Differentiation of osteoclasts.

Osteomalacia
• Blood test.
-Reduced Ca2+.
-Mildly reduced PO43-.
-Raised alkaline phosphatase.
• X-ray.
-Bone rarefaction.
-Looser's zones (linear rarefaction) in femoral cortex.

Osteoporosis
• Average 0.7% bone loss per year (normal).
• Peak bone mass.
• Physical activity.
• Ageing effects on osteoblasts.
• Genetic factors (vitamin D receptor affinity).
• Hormonal environment.

Paget's disease of bone
• Blood tests.
-FBC normal for age.
-Marked rise in alkaline phosphatase.
• Features.

Osteopetrosis
• Marble bone disease.
• Inherited osteoclast defect.
• Brittle bones even though dense and heavy.
-Autosomal recessive malignant type.
§Fatal early in life.
-Dominant benign form.
§Fractures in adolescence.

Healing of bone
• Fracture → haemorrhage.
-Inflammation.
-Necrosis locally.
-Granulation tissue - small blood vessels growing into necrosed tissue.
• Provisional callus.
-Woven bone with cartilage islands.
• External callus.
• Remodelling.
-Possible sources of failure.

Sadly, no notes for the second plenary due to sodding comm skills.

Anticoagulation: Drugs For Treatment And Prevention Of Thrombosis

5.1.07

Haemostasis and thrombosis
• Haemostasis: complex normal and physiological responses and control mechanisms that ensure limited blood loss following tissue damage and maintain circulating blood in fluid state.
• Thrombosis: abnormal and pathological responses which occur as a consequence of disorders/imbalance of control mechanisms.

Structure of thrombus
• Venous/arterial.
• Endothelial damage.
• Platelet aggregation.
• Activation of clotting cascade.
• Deposition of fibrin.
• Formation of thrombus.


• Subsequent degradation of formed clot.

Diseases caused by thrombus
• MI and unstable angina.
• Arterial thrombosis.
• Thrombotic strokes.
• Venous thrombosis.
• PE.

Coagulation factors
• Factors I - XIII.
• Protein C.
• Protein S.
• Factor IV = Ca2+ ions.
• Factor VI = activated factor V.

Drugs
• Heparins.
• Oral anticoagulants e.g. warfarin.
• Thrombolytics.
• Anti-platelet agents.
• Other drugs.

Heparins
• Naturally occurring mucopolysaccharide.
• Binds and enhances antithrombin III.
• Inhibits clotting factors (IXa, Xa, XIa) and thrombin.
• Dosed parenterally (IV, SC) - adjusted according to APTT.
• Short half-life.
• Low-molecular weight heparins (e.g. dalteparin, enoxaparin) dosed according to body weight and have longer half-life.
• Side effects: bleeding, thrombocytopenia, osteoporosis, hair loss.
• Reversal: protamine (binds to heparin).

Oral anticoagulants
• Warfarin (others, e.g. phenindione, rarely used).
• Inhibits vitamin K-dependent clotting factors (prothrombin II, VII, IX, X, protein C, protein S) - produced in liver.
• Onset of action 48-72 hours (needs to clear factors already formed and circulating).
• Monitored using INR - target value depends on type of clot.

Warfarin
• Metabolised by cytochrome p450 enzymes.
• Protein binding 99%.
• Numerous interactions:
-Potentiate - antibiotics, cimetidine, fluconazole etc. (inhibit p450 or protein displacement).
-Antagonise - anti-TB drugs, anti-epileptics etc.
• Side effects: bleeding, teratogenic.
• Reversal: FFP (rapid), vitamin K.

Thrombolytics
• Streptokinase, Alteplase.
• Activate plasminogen to plasmin.
• Break down established clot.
• Major uses:
-Early MI where reperfusion beneficial.
-Life-threatening PE.
• Contraindications:
-Active peptic ulcer.
-Bleeding disorders.
-Severe hypertension.
-Recent CVA.
-Recent surgery/trauma.
• Side effects: bleeding, allergy (streptokinase).
• Reversal: short half-life, tranexamic acid (inhibits fibrin breakdown).

Anti-platelet drugs
• Oral: aspirin, dipyridamole, clopidogrel.
• Parenteral: prostacyclin.
• Thromboxane A2 and ADP released by activated platelets.
• Thromboxane A2 triggers further platelet aggregation.
• Aspirin inhibits cyclo-oxygenase, which decreases thromboxane A2.
• Clopidogrel inhibits ADP-induced platelet aggregation.
• Side effects: gastric ulceration, hypersensitivity.

Other drugs
• Glycoprotein IIb/IIIa inhibitors:
• Glycoprotein IIb/IIIa:
-Binds VWF (platelet adhesion, carrier for factor VIII).
-Binds fibrin.
• Glycoprotein IIb/IIIa inhibitors block fibrinogen binding to platelets.
• Administered parenterally.
• Expensive! E.g. Abciximab.

Clinical uses
Indication Criteria Treatment Notes
MI Clinical history and ECG Aspirin, fibrinolytics (<6hours) Bleeding, allergy, reperfusion arrhythmias, short door→needle time
Unstable angina, non-STEMI Chest pain
Refractory chest pain Aspirin and heparins ? + GP IIb/IIIa inhibitors
PEs Proven/suspected Heparin followed by warfarin Heparin in pregnancy
DVT Proven/suspected Heparin followed by warfarin Heparin in pregnancy
DVT prophylaxis At risk (dehydration, pre-/post-op, immobility) Low-dose heparin
Prevention of stroke Recurrent TIAs
AF
Valve replacement Aspirin
Warfarin
Warfarin
INR 2-3
INR 3-4

Bone: Structure, Function And Remodelling

5.1.07

Functions of bone
• Mechanical:
-Protection.
-Support for other organs.
-System of levers.
• Metabolic function:
-Store for calcium (hypocalcaemia causes tetany).

Joint tissues
Fibrocollagenous
Tendon, ligament, capsule Resists tension Collagen I
Bone Resists compression Collagen I
Mineral
Cartilage Resists compression Collagen II
Proteoglycan
Water

Bone
• Organised in 2 distinct forms:
-Compact bone (cortical bone) - high proportion of bone with few spaces.
-Cancellous/spongy/trabecular bone - low proportion of bone and a lot of space.
• Cancellous bone composed of network of rods and plates called trabeculae.

Bone matrix
• Type I collagen, bone proteoglycan and some non-collagenous proteins: osteocalcin, osteonectin.
• Mineral hydroxyapaptite - a complex calcium phosphate salt.
• Collagen can be laid down into distinct patterns:
-WOVEN BONE, an immature form with random fibre orientation, laid down during rapid growth and fracture repair.
-LAMELLAR BONE, which is composed of successive layers of collagen fibres with distinct orientation.

Structure
• Long bones composed of cylindrical shaft (diaphysis) connected to expanded ends of bone (epiphyses).
• Shell of compact bone surrounds medullary/marrow cavity - site of production of blood cells in immature animals (red marrow), but becomes progressively replaced by inactive yellow marrow, mainly composed of adipose tissue.
• Spongy bone occupies medullary cavity at epiphyses - extends in to metaphysis.

Bone cells
• Osteoblasts:
-Principal function: bone formation.
-Form epithelioid layer on bone surface.
• Osteocytes - osteoblasts engulfed in bone matrix during apposition.
• Lining cells:
-Osteoblasts which have completed phase of synthetic activity.
-Can be reactivated.
• Osteoclasts - large multinucleate cells that "eat" bones.

Osteoid = Bone matrix that has not yet mineralised - mineralisation process still not understood.

Bone remodelling
• Resting.
• Activation.
• Formation - mesenchymal stem cells - osteoblasts.
• Resorption.
• Reversal.

Module 2.07

The Grandmother's Fall.
5.1.07 - 12.1.07.