What causes gout?
The over-production and/or under-excretion of urate
What are the 2 main types of drugs used in urate lowering therapies?
- Xanthine oxidase inhibitors
- Uricosuric agents
What are the main organs involved in calcium homeostasis?
What hormone controls the activity of renal 1α-hydroxylase?
PTH; its stimulates its activity
What is the outcome if infective arthritis is treated?
- 50% morbidity
- Up to 50% mortality (average is 10%)
What factors determine the type of drug treatment used in gout?
- Number of previous attacks
- Degree og hyperuricaemia
- Presence of reversible factors
- Presence of tophi
What is pseudogout?
- It is similar to gout with red, warm, swollen painful joint.
- Calcium pyrophospahte crystals instead of urate.
- Affects mainly elderly women
- Longer attacks
What type of gout are tophi usually seen?
What is the prognosis if infective arthritis is left untreated?
- Rapid joint destruction
- Sinus/ abscess formation
- Multi-organ failure
What uricosuric agents are available to prescribe in the UK?
What are the non-modifiable risk factors for gout?
- Age - over 40 for males
- Male gender
- Impaired renal function
What molecule is the precursor for Vitamin D synthesis?
Describe a chondral lesion
- Lie entirely within cartilage
- Do not penetrate subchondral bone
- Do no heal spontaneously
What medications does allopurinol interact with?
How do xanthine oxidase inhibitors help lower urate in gout?
The reduce the amount of uric acid produced, therefore preventing crystal formation
What is gout?
A clincal syndrome caused by an inflammatory response to monosodium urate monohydrate crystals
What enzyme acts on Vitamin D3 and where is it found?
Found in the liver
What are the functions of Vitamin D3 on each of the calcium homeostasis organs?
- Stimulate transport of Ca2+ and PO43- in the small intestine
- Increases serum Ca2+
- Stimulate terminal differentiation of OC directly and via OB
- Increases serum Ca2+
- Inhibit transcription of the PTH
- Decreases production (negative feedback regulation)
What is the main treatment option of advanced OA or a very large cartilage defect?
Total joint replacement
What xanthine oxidase inhibitors are availiable to prescribe?
What enzyme is essential for the breakdown of purines into urate?
What are the sources of calcium influx into the bloodstream?
Intestinal absorption and bone resorption
What are the treatment options for small/intermediate cartilage lesion?
- Osteochondral graft
- Cell based therapies
What are the main causes of monoarthritis?
- Gout/ crystal arthritis
- Trauma/ haemathrosis
- Sero-negative (Psoriatic/ IBD)
- Reactive arthritis
What are the pros and cons of mircofracture repair of a cartilage lesion?
- Defect filling
- Fibrocartilage repair
- Lasts about 5 years
- Requires futher surgery
What are the major functions of calcium within the body?
- Formationof calcified tissues
- Normal activity of nerve and muscle
- Neurotrasmitter release, hormonal and glandular secretion
- Integrity and permeability of cell membranes
- Cell adhesion
- Blood clotting
What the hormones that control blood calcium levels?
- Vitamin D3
What type of receptor is the calcium sensing receptor in the parathyroids?
It is a 7-transmembrane spanning receptor which is coupled with a G-protein
Which patients should be started on urate lowering therapy?
- After a single attack, decision based on individual characteristics
- After a second attack within a year and/or renal impairment or urate stones and/or tophi and tissue damage
What cells in the parathyroid produce PTH
What are the symptoms of a focal cartilage lesion?
- Mechanical symptoms
- Loss of function
- Joint degeneration
What are the pros and cons of osteochondral grafting?
- Defect site filled with mature cartilage
- Donor site morbidity
- Donor cartilage maybe different thickness
What are the main functions of PTH?
- Stimulates bone resorption
- Stimulates renal tubular reabsorption of calcium
- Stimulates renal 1α-hydroxylase
Descrieb osteochondral lesions
- Penetrate through vascularised subchondral bone
- Some spontaneous repair as chondroprogenitor cells invade lesion
What are the causes of the synovial fluid changes in the picture below, far left is normal
- 2nd left - Non inflammaotry disease (OA)
- Middle - Inflammatory disease (RA)
- 2nd right - Septic arthritis
- Far right - Haemarthrosis
How long after an acute attack should urate lowering therapy be started?
1-2 weeks after the inflammation has resolved
What are the symptoms of infective monoarthritis?
Sudden onset of:
- Difficulty weight bearing/ moving at all
What affect does an increase in serum calcium have on calcitonin secretion?
Increases caclitonin secretion
What investigations should be carried out if infective arthritis is suspected?
- Blood; FBC, U&E's, CRP, cultures, urate etc
- Joint fluid aspiration
What are the pros and cons of an osteotomy?
- Re-establish normal loading and gait
- Highly invasive
- Long recovery
- No repair
What are the symptoms of acute gout?
- Exquisite pain
- Usually first MTP
What are the principle goals in the treatment of gout?
- Treating acute attacks early and effectively
- Correcting hyperuricaemia
How do uricosuric agents help lower urate in gout?
They increase the excretion of uric acid from the kidneys
What investigations are carried out to confirm gout?
Joint fluid examination:
- Urate crystals seen - needle shaped and show negative birefringence under polaried light
- Baseline urate, U&Es, blood sugar and fasting lipds
- Urinalysis for blood and protein
- CRP, for acute attack
What stimulates the release of PTH?
Falling serum calcium levels
What is the best technique for focal cartilage repair?
Matrix-induced Autologous Chondrocyte Implantation (MACI)
What are some of the sources of infection for infective arthritis?
- Haematogenously - main cause
- Direct infection
- Adjacent bone
Which is the greater cause of gout, over-production of urate or under-excretion?
Under-excretion - accounts for 90% of cases
What are the risk factors for infective arthritis?
- Prosthetic joint
- Immunosuppression - elderly/diabetic
- Existing joint disease
- IV drug abuse
What enzyme in the kidneys converts 25-hydroxyvitamin D3 to 1,25 (OH)2 Vitamin D3
What is the main effect of calcitonin?
Inhibits osteoclast bone resorption
What are the pros and cons of autologous chondrocyte implantation?
- Defect filling
- Good outcomes
- Focal lesions
- Variable tissue repair
- Failure due to resumption of "high impact" activities
What properties of articular cartilage makes repair difficult?
- Avascular - no fibrin clot or chemotactic factors
- Slow diffusion of nutrients and waste from synovial capsule into synovial fluid into cartilage
What are the pros and cons of debridement of a cartilage lesion?
- Pain relief
- Altered joint congruency
- No repair
- Results last about 5 years
What are the 3 main causes of bacterial infective arthritis?
Staphylococcus aureus - most common
Gonococcus - yound adults
- E. coli/ Salomonella/ Proteus
What type of receptor is the PTH receptor?
G-protein coupled receptor
What are the modifiable risk factors for gout?
- High-purine diet
- Alcohol consumption
- Certain medication such as diuretics
What is the timecourse of an acute gout attack?
- 1-2 days
- 7-10 days
What are the drug options in the treatment of an acute gout attack?
- NSAIDs - Naproxen, Ibuprofen
- Steroid; oral or intra-articular
DO NOT start urate lowering treatment during an acute attack, or stop urate lowering therapy if already on it
What are the 4 classifications of cartilage defects
- Grade 1 - fissure into superficial cartilage
- Grade 2 - increased fibrillation and multiple fissure
- Grade 3 - fissures extending down to subchondral bone, no denuded bone
- Grade 4 - complete cartilage loss and exposure of subchondral bone
Where does urate come from?
The breakdown of purines in the body
What is a side-effect of starting urate lowering therapy that might lower compliance?
Acute gout attacks are common after starting as the urate crystals are mobilised
What are the sites of calcium removal from the blood?
Renal excretion and bone formation
Where is sterol-7-dehydrocholesterol converted into Vitamin D3?
In the skin, when UV light is shone on it
What are the 2 types of focal cartilage lesion?
- Chondral lesion
- Osteochondral lesion
What are the diagnostic criteria used in psuedogout?
- Aspirate - brick-shaped crystals
- Chondrocalcinosis sometimes seen in X-Ray
- Usually associated with hyperparathyroidism, OA, haemochromatosis, diabetes or acromegaly
What is the treatment for pseudogout?
There is no specific treatment, but give:
- Steroid injection
- Joint replacement if very severe