Pathophysiology Flashcards
What is pseudogout?
Aging cartilage degeneration: age related OA - calcium pyrophosphate crystals into joint cavity. Common in the elderly
Mineralisation around chondrocytes
Mainly asymptomatic
What are Seronegative spondyloarthropathies?
Inflammatory systemic disease involving axial skeleton (spine and sacroilliac joints), also peripheral joints. Negative to rheumatoid factor
Oligoarthritis commonly involving large joints in lower limbs
Familial clustering, & linkage to HLA-B27
Characterized by inflammation at sites of attachment of ligament, tendon, fascia, or joint capsule to bone (enthesopathy)
Includes Reiter’s syndrome, ankylosing spondylitis, psoriatic arthritis, & arthritis of inflammatory bowel disease
Occurs more third decade, commonly young men
Genetic factors important role in susceptibility
Initial event involves interaction between genetic & environment factors, particularly bacterial infections
Reiter’s syndrome may follow GI/ GU infections
Bowel inflammation implicated in pathogenesis of Reiter’s syndrome, psoriatic arthritis, & ankylosing spondylitis
What is Ankylosing spondylitis?
Erosion of sites where ligaments and tendons attach to bone at sacroiliac joint and lumbar spine. Eventual posterior fusion of spine and possible involvement of upper spine and large joints. 5x more common in men. 90% have HLA-B27 antigen
What are Reactive arthropathies?
Inflammatory joint disorders with an infective cause but distant in time and place from the infection
What is Psoriatic arthritis?
Inflammation of the joints in 5-7% of psoriasis sufferers
Most have extra spinal disease
Silver/grey scaly spots on scalp, elbows, knees and lower spine
Pitting fingernails/toenails
Pain & swelling in one or more joints
Dactylitis of fingers/toes gives “sausage” appearance
What are 3 types of autoimmunity?
Organ-specific: type 1 diabetes
Tissue-specific: myesthenia gravis
Systemic: lupus
Which cells mainly mediate autoimmunity?
B cells
Why can diagnosis of autoimmunity be difficult?
Presence of auto-antibodies in healthy patients
What are the mechanisms underlying autoimmunity?
Inappropriate access to self- antigens by antigen presenting cells (normally immuno-priviledged site exposed)
Inappropriate/increased local expression of co-stimulatory molecules (infection or inflammation)
Alterations in way in which molecules are presented to immune system
(MHC changes)
Molecular mimicry (infective agent)
What are the types of arthropathy?
Degenerative: OA
Inflammatory: Seropositive e.g. RA, Seronegative e.g. Ank Spond, Psoriatic, Inflammatory bowel disease, Gout, Infection
What are risk factors for rheumatoid arthritis?
Genetic predisposition: HLA-DR4 associated
2-3x women than men
Increases with age
Caucasians
What are symptoms of rheumatoid arthritis?
Systemic: fatigue, anorexia, weight loss, low grade fever, anaemia
Articular- joint aching and stiffness
Extra-articular: pericarditis, valve problems, atherosclerosis, pleural effusions, rheumatoid nodules, pulmonary fibrosis, anaemia, splenomegaly, osteoporosis, rheumatoid nodules, vasculitis, leg ulcers, C1/C2 atlanto-axial subluxation, nerve compression scleritis, xerophthalmia
What are clinical features in the hands of a rheumatoid patient?
Metacarpophalangeal joint & proximal interphalangeal joint arthritis with ulnar deviation
Describe the pathogenesis of rheumatoid arthritis
Rheumatic factor autoantibodies attack synovium
Inflammation of synovium: angiogenesis, proliferation
Secondary changes occur in cartilage: enzymes and prostaglandins destroy articular cartilage and underlying bone, pannus invasion destroys cartilage at joint periphery
What can cause ankylosis of joints in rheumatoid arthritis?
Reduced movement of joint due to collagen scarring building up in the joint. This can mineralise and fix the joint
Describe visible differences in the joint between RA and OA
RA: inflammation, pannus, eroding cartilage, bony & fibrous ankylosis
OA: Osteophytes, bony spur, no ankylosis, subchondral cyst, subchondral sclerosis, thinned fibrillated cartilage
What investigations can be done to diagnose rheumatoid arthritis?
Bloods
FBC : anaemia (chronic disease / haemolytic)
ESR : raised
CRP : moderately raised
Immunology: RhF : raised in ~70% of cases (also some healthy people), Anti CCP more specific marker
Radiology :
US, MR or isotope bone scans (early changes)
Radiographs of hands & feet (later changes), soft tissue swelling, juxta-articular osteopenia, joint space narrowing, periarticular erosions, subluxation, deformity
What are treatment options for rheumatoid arthritis?
Symptomatic relief: Pain killers, Glucocorticosteroids
Treatment of underlying disease process: DMARDS (Disease modifying anti-rheumatic drugs), Normally at least two
Biological agents after DMARDS have been unsuccessful
How do corticosteroids help to treat rheumatoid?
Inhibition of transcription factors
Reduced transcription of many cytokine genes e.g. ↓IL1, IL2 and TNF
Reduced clonal proliferation of T helper Cells
What are DMARDs?
Mimic endogenous compounds, Anti-cancer and immunosuppressant effects
Anti-proliferatives: Methotrexate (against folate activity), azathioprine (against purine synthesis)
Suppressive: sulphasalazine (against IL-1 & TNF), penicillamine (against MΦs, T cells, IL-1)
Gold injections = uncertain mechanism
Describe how methotrexate works
Folic acid antagonists. Inhibits dihydrofolate reductase activity which prevents conversion of dihydrofolate to tetrahydrofolate which is not all used for the production of purines and amino acids and therefore DNA and protein synthesis
Inhibits S phase
Renal excretion
Side effects - mainly affects tissues which are highly proliferative - Gi tract, liver due to anti proliferative effects
Describe how azathioprine works
Anti proliferative effects
Purine analogue
Reduce DNA & RNA synthesis so can’t go through cell cycle
Reduce guanine and adenine synthesis
Adverse effects: cholestasis, liver necrosis
What Biological Agents can be used to treat rheumatoid arthritis?
mAbs (monoclonal antibodies): infliximab = anti-TNF cytokine, rituximab = anti-CD20 on B lymphocytes
What is the prognosis for rheumatoid arthritis patients?
10% will become severely disabled, majority of damage in first 5 years
70% will have variable symptoms with flair ups requiring drug therapy 20% mild disability and symptoms
Complications: Reduced immunity, Complications of drug treatments
What questions need to be asked in a history addressing lumps and bumps?
How long have you had this? Exacerbating/alleviating factors Pain in swelling location or elsewhere History of trauma Any previous or recent treatment/intervention/surgery Site-dependent questions Neurological disturbance/distribution Temporally-associated systemic symptoms
What additional factors need to be considered when forming a diagnosis on lumps and bumps?
Age Gender Social history Occupation Medical history
What are 2 methods for lump examination?
SSSCCATTTT Site, Size, Shape, Consistency, Colour, Auscultate, Tenderness, Tissue layer, Thrills/Fluctuance, Transillumination SPACE TIT Size, Shape, Surface Position Attachments Consistency & Colour Edge Thrills/pulsation/fluctuance Inflammation Transillumination
What are methods for determining the origin/content of a lump?
Transillumination - fluid filled
Fluctuance - fluid filled
Auscultate - air, bowel sounds, pulsation, bruits
What does annular mean in relation to lumps?
Ring shaped
What does arcuate mean in relation to lumps?
Curved
What does nodule or papule mean in relation to lumps?
Palpable mass of specific size
What does macule mean in relation to lumps?
Flat region of surface colour change
What does pustule mean in relation to lumps?
Small pocket of pus
What techniques can be used to determine the tissue layer location of a mass?
Bone masses are immobile
Muscle/tendon masses can be moved, or have their movement limited, by muscle contraction
Neural masses only tend to move left-to-right
Pressing on a neural mass can cause pain/tingling/sensory loss
Lumps within the skin can be moved with the skin
What ways can you describe a skin cancer?
A – Asymmetry
B – Borders
C – Colour
D - Dimensions
How does lymphadenopathy present?
Palpable relatively non-mobile mass
Enlargement can be unilateral during cancer or infection
What are Sister Mary Joseph Nodules?
Cancer metastasis in umbilicus
Spread up urachus from bladder
What needs to be considered with groin lumps?
Can you get above the swelling? Yes: not a hernia, No: likely a hernia
Reduce a hernia and test cough impulse
Is it solid or fluid-filled? - fluid, hydrocele
Where is the lump relative to the testicle? - above: spermatocele, on testicle: Cancer
Where is the testicle? - within swelling: hydrocele
Does it look/feel like a ‘Bag of worms’? - varicocele
What is testicular pain?
Torsion until proven otherwise
What is a hydrocele? And how can you diagnose it?
Fluid in tunica vaginalis
Will transilluminate and sits at the level of the testicle
May not be able to palpate the testicle
How would a patent processus vaginalis present?
Young boy
Swelling not there in the morning but appears during the day, then disappears when lying down
Swelling transilluminates but can’t get hand above it
Peritoneal fluid communicating, gravity means it accumulates through the day
What is a hernia?
Protrusion of a tissue or organ through its retaining tissue
