Provide a brief overview of the three main types of joint degeneration
Osteoarthritis
- Presents as chronic degeneration of a few joints
- Especially hard-working hands and weight-bearing joints, or previously injured joints
- Symptoms include deep pain, worse with use
- Treatment includes physiotherapy, pain relief, and joint replacement
Rheumatoid Arthritis
- An autoimmune inflammatory arthritis with systemic involvement
- Often starts symmetrically in small joints of hands and/or feet, and proceeds to destroy them
- Morning stiffness, systemic symptoms
- Treatment involves immune modulating “DMARDs” (Disease-Modifying Anti-Rheumatic Drugs)
Gout
- Incredibly painful acute inflammation in a single joint due to crystallisation of uric acid
- often the big toe: “podagra”
- Classically in ‘portly’ gentlemen with rich diet
- associated with risk of DMT2, HTN, heart disease, etc.
- Treatment includes anti-inflammatory medication, urate lowering therapy and lifestyle changes
Characterise the pathophysiology of osteoarthritis
Traditionally considered a disease of normal wear and tear, osteoarthritis affects the capsule, synovium and underlying bone in a joint.
Damage stimulates chondrocyte proliferation, enzyme/cytokine actions and the depletion of cartilage matrix
The depletion of cartilage matrix itself results in the release of enzymes (collagenase and MMPs) that mediate loss of mechanical integrity of the collagen and thus joint function
Results in:
1. Fibrillation (non-uniform loss of cartilage)
**2. ****Continuous cycles of regeneration lead to thickened but microfractured subchondral bone
3. Bone-on-bone articulations lead to:
- **eburnation of bone **
- subchondral cysts
- osteophytes
What are the signs and symptoms of osteoarthritis?
Signs:
Reduced range of movement
Crepitus
Osteophytes
Symptoms:
Insidious onset
Pain ( deep ache + worse after activity )
No systemic symptoms
What testing is required for a diagnosis of osteoarthritis?
**A diagnosis of osteoarthritis is mostly clinical **
There are no diagnostic laboratory tests
X-rays are not always necessary
Only laboratory tests conducted are exclude differential diagnosis - particularly inflammatory arthritis where a blood test is conducted
What can x-rays of osteoarthritic joints show?
Losses in load-bearing joint space
Subchondral cysts
Subchondral sclerosis
Osteophytes
What are the risk factors for osteoarthritis?
Most factors relate to damage to joint cartilage:
- **Increasing age **
- Rare under 40, >50% over 70 years old
- **Obesity **
- Linear increase in risk with weight – especially knees
- Previous injury/abnormality of joint
- Can affect proprioception, alignment, joint surface
- **Repeated heavy use of joint **
- Work or recreational
- **Genetic **
- In hand and hip, not knee?
In which joints is osteoarthritis more prominent?
OA occurs in joints that are stressed by the mosern human’s transition to upright posture and opposable thumbs:
Hip, knee, lower lumbar vertebrae, cervical vertebrae, first metatarsophalangeal joint, first metacarpophalangeal joint and both distal and proximal interphalangeal joints
Characterise the pathophysiology of rheumatoid arthritis
Rheumatoid arthritis is a systemic inflammatory condition that is triggered by an unknown “arthrogenic antigen” in genetically susceptible individuals.
The subsequent immune response upregulates Th1 and Th17 T helper cells that produce an array of cytokines: IL-1, IL-6, IL-17 and most importantly TNF-a. These molecules induce activation of fibroblasts, macrophages osteoclasts and B-cells
The effects of these cells leads to:
- mononuclear infiltrate with germinal centres in synovium
- **Pannus formation = **inflammed and hyperplastic synovial tissue creeping over cartilage and bone tissue + histologically different from other inflammed synovium (inflammatory granulation tissue)
- Pannus invades and erodes bone and cartilage
- creates a hypoxic environment, uregulates osteoclasts and produces MMP
- Weakening and destruction of ligaments
- Eventual fibrosis and bony union of joints
What are the signs and symptoms of RA?
Signs:
- Warm + swollen joints
- rubbery or doughy feel
- Rheumatoid nodules
- Eventual destruction and deformity of joints
Symptoms:
- Systemic symptoms
- fever, weight loss, anaemia
- Morning stiffness
- __more than one hour
- eases with activity
- Symmetric polyarthritis
- usually starts in hands then feet
- distal interphalangeal joint often spared
What is a rheumatoid nodule?
Rheumatoid nodules are patches of granulomatous inflammation
The node consists of areas of central necrosis surrounded by epithelioid macrophages, lymphocytes and fibrosis
Occasionally, multinucleate giant cells are present
What testing is conducted in the diagnosis of rheumatoid arthritis?
General inflammatory tests = CRP, ESR, FBE
Rheumatoid factor test
Anti-cyclic citrullinated peptide (anti-CCP)
X-ray imaging
Diagnosis depends on correlating clinical findings with the tests listed above
What x-ray findings are likely in a pateint with RA?
Juxta-articular osteopaenia
- early pattern of bone loss in cancellous/trabecular bone near the affected joint
Sub-chondral erosions
- loss of cortical bone directly underlying the **pannus **of a RA joint
Uniform joint space loss
- indicates the loss of cartilage superficial articular bone layers
What are the risk factors for RA?
Prevalence: ~1% of population
Genetic (~50% of risk):
- shared epitopes of HLA-DRB1; PTPN-22
- imprinting and epigenetics
Female gender (2-5:1)
Increasing age
- from ~25 until ~55y.o..
Smoking
- RR= 1.3-3.5
Characterise the pathophysiology of Gout
Gout is a metabolic disease caused by the excessive accumulation of uric acid in the body
Uric acid **precipitates **in cool areas with low pH and nucleating agents (synovial fluid is a poor solvent - predisposes to crystal precipitation) particularly after alcohol, dehydration, or dietary indiscretion
Most commonly affects the big toe metatarsophalangeal joint = podagra
The precipitating uric acid crystals activate inflammatory cells, synovial cells and **complement cascade **in an *acute gout attack. *
IL-1 is a particularly dominant organiser of immune response
Gout can progress into a chronic, disabling ‘tophaceous gout’ if left untreated
- involves multiple joints
- recurrent inflammation causes damage pannus formation
- urate deposition in other tissues = tophi
- cartilage, joint capsules etc.
- Development of gouty nephropathy and kidney stones
How are uric acid crystals stained for?
Uric acid crystals are **negatively bifringent in polarised light **
This means that the crystals turn differnt colours depending on the direction they are facing when polarised light is directed upon them
Describe the histological appearance of tophi
Gouty tophus is characterised as a state of granulomatous inflammation (foreign body type)
**Central urate deposits **are surrounded by epithelioid macrophages and multi-nucleate giant cells
A ring of fibrosis and fibroblasts enclose these cell types
What are the signs and symptoms of gout?
Signs:
- Acutely inflamed joint
- Seldom systemically unwell
- if often systemically unwell - investigate septic arthritis arising from an infected tophi
- Tophi if chronic
Symptoms:
- Spontaneous onset of excrutiating pain, swelling, heat and redness
- classically in the big toe early in the morning
What testing is required for a diagnosis of Gout?
Gold standard is joint (or tophus) aspiration
“negatively birefringent crystals” with neutrophils
Serum urate is confusing and is not particularly reliable in diagnosis:
- an acute gout attack can lower serum urate
- urate-lowering therapy can precipitate gout
- most people with high urate do not have gout
X-rays have little role in diagnosis; but are impressive in ascertaining damage in late stage gout:
- Punched-out erosions with sclerotic, overhanging edges
- Outside of the joint capsule
- Tophi may be visible – even calcified
- Asymmetric distribution
- No loss of joint space
- No periarticular osteopaenia
What are the risk factors for Gout?
**Prevalence: **
- 2% of men >30y.o.
- 9% of men >80y.o.
- 2% of women >50y.o.
- 6% of women >80y.o.
It is high in males, increases with age and menopause.
- Uric acid metabolism
- Increased intake or production
- Reduced excretion
- competes with alcohol for secretion in kidneys
- Genetics and ethnicity
- Obesity, hypertension, metabolic syndrome
What is the relevance of urate oxidase function to evolution?
Upright-walking hominids are the only known eukaryotes without functioning urate oxidase genes
High uric acid is related to sodium retention / hypertension -> elevates blood pressure -> better perfusion of the upright brain
