MSK & Rheumatology Flashcards
cortical v trabecular bone?
cortical
- compact
- only spaces for cells and blood vessels
trabecular
- spongy
- many holes filled with bone marrow
woven v lamellar bone
woven
- made quickly
- disorganised
lamellar
- made slowly
- organised
adult bone composition?
50-70% mineral - HYDROXAPATITE (crystaline form of calcium phosphate)
20-40& organic mix - type 1 collagen and non collagenous proteins
5-10% water
MINERAL = STIFF COLLAGEN = ELASTIC
OSTEOARTHRITIS (OA):
Cartilage loss with accompanying periarticular (around the joint) bone response
• Inflammation of articular (actually in contact with bone) and periarticular structure
and alteration in cartilage structure
epidemiology of oesteoarthiritis?
- > 55
- F>M
risk factors of oesteoarthritis
- joint hyper-mobility
- diabetes
- increasing age
- genetic predisposition
- obesity -> pro inflammatory state
- occupation
- local trauma
- inflammatory arthritis
pathophysiology of oesteoarthisits?
Progressive destruction and loss of articular
cartilage with an accompanying periarticular
bone response
- Cartilage is a matrix of collagen fibres,
enclosing a mixture of proteoglycans and water;
it has a smooth surface and is shock-absorbing
- Under normal circumstance, there is a dynamic
balance between cartilage degradation by wear and its production by
chondrocytes
- Early in the development of OA this balance is lost, the cartilage become oedematous
- Subsequently focal erosion of cartilage develops and chondrocytes die
Cartilage ulceration exposes the underlying bone to increased stress,
producing micro-fractures and cysts
- The bone attempts repair but produces abnormal
SCLEROTIC SUBCHONDRAL BONE and overgrowths
at the joint margins which become calcified - known as
OSTEOPHYTES
There is also some secondary inflammation
clinical presentation of oesteoartheritis?
Symptoms are usually gradual in onset and progressive
- Joint pain - made worse by movement and relieved by rest
- Joint stiffness after rest (gelling)
- transit morning stiffness
- nodes and bone swellings at DIPJ
investigations of oesteoarthritis
- CRP can be elevated
- negative RF and ANA
- XRAY (LOSS (loss of joint space, osteophytes, subarticular sclerosis and subchondral cysts)
treatment of oesteoarthritis?
- non medical; exercise, weight loss, alternative therapy
- pharm - paracetamol, opiods and intra-articular corticosteroid injections
- surgery; arthroscopy, arthroplasty
rheumatoid arthritis
A chronic systemic AUTOIMMUNE disorder causing a SYMMETRICAL
POLYARTHRITIS
disease of synovial joints
epidemiology of rheumatoid arthritis?
- 30-50 yrs peak age
- F>M
risk factors for rheumatoid arthritis?
- female -> oestrogen
- genetics -? HLA DR4
- smoking
- family history
- immune system
pathophysiology of rheumatoid arthritis?
RA is primarily a synovial disease and synovitis
(inflammation of the synovial lining) occurs when
chemoattractants produced in the joint recruit
circulating inflammatory cells
- Over-production of TNF-alpha leads to synovitis
and joint destruction - the interaction of
macrophages, T and B lymphocytes drives this overproduction In RA the synovium becomes greatly thickened and becomes infiltrated by
inflammatory cells
Generation of new synovial blood vessels is induced by angiogenic
cytokines and activated endothelial cells produce adhesion molecules which
FORCE LEUCOCYTES into the synovium - where they can trigger
inflammation
- The synovium proliferates and grows
out over the surface of the cartilage
(past the joint margins), producing a
tumour-like mass called ‘pannus’
- This pannus of inflamed synovium
DAMAGES the underlying cartilage
by blocking its normal route for
nutrition and by direct effects of
cytokines on the chondrocytes
- The cartilage becomes thin and the underlying bone exposed
- The pannus DESTROYS the articular cartilage and subchondral bone
resulting in bony erosions
clinical presentation of rheumatoid arthritis?
- usually MCP and PIP
- joints warm and tender
- morning stiffness > 30 mins
- symmetrical
- hand deformities; swan neck
- pain eases with use
- extra-articular; lungs (pleural effusion), heart (pericarditis), eyes (scleritis), neurological (carpal tunnel, cord compression, peripheral sensory neuropathies), kidneys (amyloidosis) and subcutaneous nodules in skin
investigations for rheumatoid arthritis?
- FBC ; low hB, ESR AND CRP raised, RF positive and ANTI CCP positive
- XRAY (soft tissue swelling, joint space narrowing and peri-articular erosions)
- MRI and USS
rheumatoid arthritis tretament?
- lifestyle changes
- pain management -> NSAIDs and PARACETAMOL
- corticosteroids (can risk osteoporosis)
- DMARD (inhibits inflammatory cytokines) eg METHOTEXTRATE (GOLD STANDARD)
- biological therapy (TNF alpha blocker eg, INFLUXIMAB) , B cell inhibitors (RITUXIMAB - CD20)
osteoporosis?
A systemic skeletal disease characterised by low bone mass and a micro
architectural deterioration of bone tissue, with a consequent increase in
bone fragility and susceptibility to fracture
bone mineral density (BMD) MORE than 2.5 standard deviations
BELOW the young adult mean value (T score < 2.5)
osteopenia?
Pre-cursor to osteoporosis characterised by low bone density - Defined as BMD between 1-2.5 standard deviations BELOW the young adult mean value (-1< T score < 2.5)
osteomalacia?
Poor bone mineralisation leading to soft bone due to lack of Ca2+
epidemiology of osteoporosis?
- > 50 yrs
- F>M (women lose trabecular with age)
- Caucasian and asians
risk factors for osteoporosis?
- old age
- women
- family history
- smoking
SHATTERED
S - steroid use
H - hyperthyroidism/hyperparathyroidism (increase bone turnover)
A - alcohol and tobacco
T - thin (BMI <22)
T - testosterone decreased
E - early menopause
R - renal or liver failure
E - erosive/inflammatory bone disease
D - dietary calcium decreased
pathophysiology of osteoporosis
Osteoporosis results from increased bone breakdown by osteoclasts and
decreased bone formation by osteoblasts, leading to loss of bone mass
Genetic factors are the SINGLE MOST SIGNIFICANT INFLUENCE on peak
bone mass
Bone strength is determined by bone mineral density, bone size and bone quality (mineralisation)
Oestrogen deficiency - Postmenopausal osteoporosis:
• Results in increased numbers of remodelling units (osteoclasts),
premature arrest of osteoblastic synthetic activity and perforation of
trabeculae with a loss of resistance to fracture
• High bone turnover (resorption greater than formation)
Changes in trabecular architecture with ageing:
• Decrease in trabecular thickness - as we age the strain is felt on bones
from head to tail, in response, we tend to preferentially preserve
VERTICAL TRABECULAE and LOSE HORIZONTAL TRABECULAE
clinical presentation of osteoporosis
- fractures
- colles fracture of wrist
investigations of osteoporosis?
- XRAY
- DEXA SCAN (GOLD STANDARD)
- FBC; ca2+, phosphate
treatment of osteoporosis?
- lifestyle changes
- pharma -> anti-resorptive drugs eg BISPHOSPHONATES (1st line ORAL ALDENIDRONATE), DENOSUMAB (inhibits RANK)
- HRT for menopausal women (RALOXIFENE)
ESR V CRP
ESR
- rises and falls slowly
CRP
-rises and falls rapidly
SLE?
An inflammatory, multisystem autoimmune disorder with arthralgia and rashes
as the most common clinical features, and cerebral and renal disease as the
most serious problems
epidemiology of SLE?
- F>M
- Peak age of onset between 20-40 yrs - typically women of childbearing age
- Commoner in African-Caribbeans and Asians
risk factors of SLE?
Family history - Genetics: • HLA genes have been linked to SLE - Pre-menopausal women MOST AFFECTED - Drugs: • Hydralazine, isoniazid, procainamide and penicillamine - UV light can trigger flares of SLE - Epstein-Barr virus is a potential trigger for SLE
pathophysiology of SLE>
When cells die by apoptosis, the cellular remnants appear on the cell surface
as small blebs that carry self antigens
- These antigens include nuclear constituents such as DNA and histones,
which are normally hidden from the immune system
- In SLE, removal of these blebs by phagocytes is inefficient, so that they are
transferred to the lymphoid tissues, where they can be taken up by antigen-
presenting cells
- These self-antigens from these blebs can then be presented to T cells, which
in turn stimulate B cells to produce AUTOANTIBODIES directed against the
antigens - Can be years before clinical features develop
clinical presentation of SLE?
Most patients suffer fatigue, fever, arthralgia and/or skin problems
- joint involvement - symptoms similar to RA
- skin involvement - butterfly erythema on cheeks, photosensitive rash
- lung involvement - pleural effusions
- heart involvement - pericarditis
- kidney - glomerulonephritis with persistent proteinuria
- CNS - seizures and psychosis
- eyes - Sjornes
- GI - month ulcers
investigations of SLE?
- blood; raised ESR and normal CRP, low Hb, low WCC
- autoantibodies - ANA positive, anti dsDNA (specific but only positive in 60%)
- histology - deposition of IgG
- MRI and CT
treatment of SLE?
IV CYCLOPHOSPHAMIDE + HIGH DOSE PREDNISOLONE
- reduce sunlight exposure, wear sunblock
- symptomatic; NSAIDs, corticosteroids for rashes
- ANTIMALARIAL drugs e.g. CHLOROQUINE OR HYDROXYCHLOROQUINE
help mild skin disease, fatigue and arthralgia that cannot be controlled by
NSAIDs - but watch for retinal toxicity - ORAL METHOTEXTRATE
- RITUXIMAB
antiphsopholipid syndrome?
Syndrome characterised by thrombosis (arterial or venous) and/or recurrent
miscarriages with positive blood tests for antiphospholipid antibodies (aPL)
antiphosphoplipid syndrome epidemiology
F>M
pathophysiology of anti-phospholipid syndrome?
Antiphospholipid antibodies (aPL) play a role in thrombosis by binding to
phospholipid on the surface of cells such as endothelial cells, platelets and
monocytes
- Once bound, this change alters the functioning of those cells leading to
thrombosis and/or miscarriage
- Antiphospholipid antibodies (aPL) cause CLOTs:
• Coagulation defect
• Livedo reticularis - lace-like purplish discolouration of skin
• Obstetric issues i.e. miscarriage
• Thrombocytopenia (low platelets)
clinical presentation of anti-phospholipid syndrome?
- Thrombosis
- Miscarriage
- Ischaemic stroke, TIA, MI - arteries
- Deep vein thrombosis, Budd-chiari syndrome - veins
- Thrombocytopenia
- Valvular heart disease, migraines, epilepsy
investigations of anti-phospholipid syndrome?
Anticardiolipin test:
• Detects IgG or IgM antibodies that bind the negatively charged
phospholipid - cardiolipin
- Lupus anticoagulant test:
• Detects changes in the ability of the blood to clot
- Anti-B2-glycoprotein I test:
• Detects antibodies that bind B2-glycoprotein
treatment of anti-phospholipid syndrome?
Long term WARFARIN to minimise thrombosis
- Pregnant women:
• ORAL ASPIRIN and SC HEPARIN early on in pregnancy
• Reduces chance of miscarriage but pre-eclampsia and poor fetal
growth remain common
- Prophylaxis:
• ASPIRIN or CLOPIDOGREL for people with aPL, especially those with a
high IgG aPL (antiphospholipid antibody)
sjorgrens syndorme?
Chronic inflammatory autoimmune disorder
• Characterised by immunologically mediated destruction of epithelial exocrine
glands, especially the lacrimal (eyes) and salivary glands
epidemiology of sjorgrens syndrome?
F>M
40-50 yrs
family history
pathophysiology of sjorgrens syndrome?
Lymphocytic infiltration and fibrosis of exocrine glands, especially the
lacrimal and salivary glands
clinical presentations of sjorgrens syndrome?
Dry eyes (keratoconjunctivitis sicca) - due to decrease in tear production
- Dry mouth due to decreased saliva production (xerostomia)
- Salivary and parotid gland enlargement
- Dryness of the skin and vagina may be a problem
can have systemic symptoms dysphagia, myasthenia graves, vasculitis
investigations of sjogrens syndrome?
Schirmer tear test:
• Strip of filter paper is placed on the inside of the lower eyelid; wetting of
< 10 mm in 5 mins indicated defective tear production and thus
Sjogrens
- Rose Bengal staining:
• Staining of the eyes shows punctate or filamentary keratitis
FBC
- raised immunoglobulins
- RF positie
- ANA positive
treatment of sjorgrens syndrome?
- artificial tears and saliva replacement
- HYDROXYCLOROQUINE
systematic sclerosis?
• Multisystem disease with involvement of skin and Raynauds phenomenon
epidemiology of systemic sclerosis?
F>M
30-50 yrs
risk factors of systemic sclerosis?
- Exposure to vinyl chloride, silica dust, adulterated rapeseed oil and
trichloroethylene - Drugs such as bleomycin
- Genetic
pathophysiology of systemic sclerosis?
Widespread vascular damage involving small arteries, arterioles and
capillaries is an early feature
- There is initial endothelial cell damage with release of cytokines, including
endothelin-1, which causes vasoconstriction
- Continued vascular damage and increased vascular permeability and the
activation of endothelial cells leads to inflammation
- this causes fibrosis in the lower dermis of skin and internal organs
- The end result is uncontrolled and irreversible proliferation of connective
tissue and thickening of vascular walls with narrowing of the lumen - Damage to small blood vessels also produces widespread obliterative
arterial lesions and subsequent chronic ischaemia
clinical presentation of systemic sclerosis?
- Raynaud’s phenomenon
- digital pits or ulcers
- swelling of the hands and feet
- fatigue
dry cough
decreased exercise tolerance
weight loss
investigations of systemic sclerosis?
- FBC -> low Ebb
- autoantibodies - ACAs and ANA postive
- imaging
- urinalysis
treatment of systematic sclerosis?
- no cure
- help with symptoms; oral vasodilators CCB, PPPI, ACE inhibitors (prevent renal crisis)
polymyositis?
rare muscle disorder of unknown aetiology in which there
is inflammation and necrosis of skeletal muscle fibres
When the skin is involved it is called dermatomyositis (DM)
epidemiology and risk factors of polymyositis
- F>M
- risk factors virus eg COXSACKIE and genetic predisposition of sjorgrens
clinical presentation of polymyositis and dermatomyositis
Polymyositis (PM):
• There is symmetrical progressive muscle weakness and wasting
affecting the proximal muscles of the shoulder and pelvic girdle
• Patients have difficulty squatting, going upstairs, rising from a chair
and raising their hands above their head
• Pain and tenderness are uncommon
• Involvement of pharyngeal, laryngeal and respiratory muscles can lead
to dysphagia, dysphonia (difficulty speaking) and respiratory failure
Dermatomyositis (DM):
• Characteristic skin changes; heliotrope (purple) discolouration of the
eyelids and scaly erythematous plaques over the knuckles (Gottron’s
papules)
• Arthralgia, dysphagia resulting from oesophageal muscle involvement
and Raynauds phenomenon
• DM is associated with an increased incidence of underlying malignancy
investigations of polymyositis
- GOLD STANDARD - muscle biopsy
- muscle enzymes; Serum creatine kinase, aminotransferases, lactate dehydrogenase
(LDH) and aldolase are ALL RAISED - ESR not raised
- ANA positive and can have RF positive
treatment of polymyositis?
- bed rest
- ORAL PREDNISOLONE
- ORAL METHOTEXTRATE for relapse
reynauds phenomenon?
Consists of intermittent spasm in the arteries supplying the fingers and toes
usually precipitated by cold and relieved by heat
- no underlying cause of disease but underlying cause in phenomenon
epidemiology of raynauds phenomenon?
F>M
pathophysiology of raynauds phenomenon
Peripheral digit ischaemia due to sudden vasospasm, precipitated by cold or
emotion and relieved by heat
- Usually bilateral and fingers are affected more commonly than toes
clinical presentation of raynauds phenomenon
Vasoconstriction (causing ischaemia) causes skin pallor followed by
cyanosis (deoxygenation) due to sluggish blood flow, then redness due to
hyperaemia - white, blue then red
- numbness and burning sensation
treatment for raynauds phenomenon
- avoid cold
- stop smoking
- vasodilators eg, NIFEDIPINE
SERONEGATIVE SPONDYLOARTHROPATHIES/SPONDYLOARTHRITIS (SpA):
Group of overlapping conditions that all share certain clinical features:
- Axial inflammation - spine and sacroiliac joints
- Asymmetrical peripheral arthritis
- Absence of rheumatoid factor hence ‘seronegative’
- STRONG ASSOCIATION with HLA-B27 - but aetiological relevance is unclear
HLA B27
Class I surface antigen - present on all cells, except RBCs
- Encoded by Major Histocompatibility Complex (MHC) on chromosome 6
- Most common in the northern hemisphere - 9% in UK, very rare in sub-
Saharan Africa - Main theory is ‘molecular mimicry’ whereby an infection triggers an
immune response and the infectious agent has peptides very similar to
the HLA-B27 molecules so there is an auto-immune response triggered
against HLA-B27
seronegative spondyloarthropathies (SpA) mnemonic?
SPINEACHE:
Sausage digit (dactylitis)
- Psoriasis
- Inflammatory back pain
- NSAID good response
- Enthesitis (particularly in heel - plantar fasciitis)
- Arthritis
- Crohn’s/Colitis/elevated CRP (can be normal in AS)
- HLA-B27
- Eye (uveitis)
ankylosing spondylitis?
Chronic inflammatory disorder of the spine, ribs and sacroiliac joints
• Ankylosis = abnormal stiffening and immobility of joint due to new bone
formation
