Rheumatology Flashcards
Bone growth stimulators
Vit D- for Ca2+ absorption
Oestrogen and progesterone- inhibit bone resorption
Calcintonin- Opposes PTH
Bone resorption stimulators
Parathyroid hormone- Controls Ca2+ in your blood,
Thyroid hormone and interleukin 1- affect osteoclasts leading to resorption
Smoking and alcohol on osteoporosis
Suppression of thyroid hormone and vitamin D and affects Ca2+ absorption
Calcium reccomendations
1000mg for men 50-70
13000mg for women >50 and men >70
Corticosteroids and osteoporosis
decrease Ca2+ intestinal absorption, increased Ca2+ renal excretion,
Drugs that affect osteoporosis
Corticosteroids, anti-eptileptics, prostate and Breast cancer hormone replacement, heparin,
Treatment of osteoporosis
Biophosphonates- fosamax: increase osteoclast apoptosis,
Selective oestrogen receptor modulators (SERMs): acts on bone like normal oestrogen
HRT: normalise oestrogen levels, slows bone loss, increased CVD risk though
Osteomyelitis inflammatory phase
Phase 1:
acute inflammation and exudate into the bone, increase lymphocytes, intraosseus pressure
Osteomyelitis Suppartion phase
Phase 2:
Pus formation after 48-72 hours, as pressure increases it travels through Volkmann canals, bursts through perisoteum , and spreds into soft tissues and joints (septic arthritis)
Osteomyelitis necrosis phase
Phase 3:
Intraosseus pressure impairs endosteal blood supply. leads to periosteal stripping and formation of sequestrum: segment of dead bone with no blood supply and surrounded by pus
Osteomyeltis formation of new bone phase
Phase 4: 10-14 days
periosteum forms new bone allowing involucrum to surround sequestrum
Diagnosing osteomyelitis
Rasied ESR, biopsy, x-ray, MRI, radionucleide scan
Pathophysiology of osteoarthritis
when matrix degeneration ezymes are overexpressed leading to loss of collagen and proteoglycans in the cartilage.
Matrix metalloprotineases, colagenase and protease are secreted which leads to stimulatio of IL1. This all leads to breakdown of proteglycans and collagen causing breaking and cracking of cartilage (joint mice). MOre pressure on the bone leads to osteophytes and thickening of synovium
Normal healthy cartilage
Has chondrocytes and ECM which:
decrease friction
Resist tension via type II collagen
Resist compression via proteglycans
OA vs RA
OA is assymetrical
RA affects MCP and PIP
OA affects DIP and PIP
Macrophage role in the RA joint
macrophages release IL1 and IL6, stimulation of fibroblasts and synoviovytes.
These then proliferate and release RANKLand proteases
Proteases break down cartilage and RANKL+ cytokineases cause osteoclast activation
T cells role in the RA joint
make up 50% of synovial cells
Promote inflammation and release IL17
Promote macrophage activity and fibroblast and RANKL ex expression
Plasma cells in RA
5% of cells in synovium. release cytokines and antibodie
SYnovial fluid role in RA
has neutrophiles which release ROS and proteases which leads to bone adn cartilage erosion
Porphyromonas ginigivalis
Potenital casue of RA
a bacteria that causes the modification of autoantigens leading to an immune response. amino acid arginine becomes citrulline
Infection leading to RA
Infection > cytokine release and inflam > citrillination of autoantigens > seem foreigen and recognised by antigen presenting cells > immune response initiaed > antigen presenting cells activate Cd4 T cells > activate B cells in germinal layer of lymph node > production of plasma cells > production of antibodies> CD4 T, antibodies and Plasma cells migrate to joint
Antibodies involved in RA
pl factor- IgM antibody target igG antibodies to form an immune complex that can deposite in synovial tissue
Anti-citrullinated protein antibody- they take fibrin and fillarin and target citrillinicated proteins: specific to RA
Extra-aeticular invovlement RA
anemia, fatigue, depression, osteopoeina, insulin resistance in muscles, infection, thrombus
Seronegative spondyloarthropathy
group of diseases related to HLA B27 gene includes AS, PA and reactive arthritis
Diseases associated with AS
weightloss, fatigure, chest pain, enthesitis, anemia, anterior uveities, aortitis, IBS, heart block
Schobers test
assesses mobility of LS
locate l5 and mark a point 5cm below and 10cm above. Get pt to bend forward, and meeasure distance between points, if it is < 20cm then there is lumbar restriction
AS radiological findings
Bamboo spine: late stages, squaring of vertebral bodies
Subchondral sclerosis
Subchondral erosion
Syndesmophytes (bony growth from where ligament attaches)
Ossification (ligaments start to turn into bone)
Fusion of facet, SIJ and costovertebral joints
Management of AS pharmaceutical
- NSAIDs: ibruoprofen and naproxen, if not relief after 2-4 weeks of max dosage then switch NSAIDs
- Steroids during flares: oral, intramuscular slow release, or into joint
- TNFa mediation- monoclonal antibodies or anti-TNFa
- monoclonal antibodies for IL7
Psoriatic arthritis background and pathophysiology
T cell mediateed attack on joints in people with psoriasis.
self- antigens are seen as foreign- release of cytokines and TNFa and inflammation- keratinocytes and fibroblasts proliferate- formation of psoriatic plaque-
T cells can also activate osteobalsts and osteoclasts leading to erosion and ossification
Types of psoritatic arthritis
Oligoarticular: asymmetrical, <5 joints
polyarticular: resemble RA, > 5 joints,
Spondylarhtiris: affects spine and SIJ
DIP predmominant: dactylitis, joint and bone deformintes
Arthritis mutlians: bone eroision with telescopic digits opera glass hands
Diagnosis of PA
blood test for rheumatoid factor and anti-citrullination; absent in PA
x-ray for erosin and pencil in cup
Treatment PA
NSAIDs
Immunomodulatory drugs
TNF inhibitors
IL12 and 23 inhibitor
Systemic lupus erythematous
SLE with joint manifestations or discoid lupus: more skin less joint and organ
An autoimmune disease that has multi-system involement
CT disease, over production of auto-antibodies
Pathogensis of SLE
Results from recurrent activation of the immune system of T and B cells from genetic or environmental disorders
Cascade of inflammation that deposits into the tissues
RIsk factors SLE
siblins, women of childbearing age, UV over exposure, EBV, drug induced, high oestrogen, OCP, pregnancy
Clinical presentation of SLE
Malar butterfly rash, photosentsitve Discoid rash: raised scaly lesion Alopecia hives raynauds bilateral and symmetrical arthritis, joint destruction, Renal nephritis anemia, leukopoenia, thrombocytopoenia, Non-specific ss
Diagnosis of SLE
antinuclear antibodies, 98% sensitive double stranded DNA ENA antibodies raised ESR or CRP Direct coombs test: detects autoimmune haemoltyic anaemia becasue it breask down RBCs
Management
MILD TO MOD: reduced enviro triggers, NSAIDs, low dose corticosteroids, antimalarias
SEVEVER: corticosteroids, immunosuppresants,
Gout
Monosodium urate crystal disorder: abnormality on uric acid metabolism that results in hyperuricaemia and urate crystal deposition in joitns, soft tissue and urinary tract
Pathogenesis of gout
Purines come together to make xanthine. xanthine oxidase converts xanthine into uric acid. we are unable to break down uric acid so we must expel it, usually xanithine via kidneys. If unable to expel it all there is a build up of the crystals which and this activates macro-hages and phagocytes creating an acute inflammatory response
Risk factors gout
genetis, renal disease, use of diuretics or salicyate, hypertensionand CHD , high purine diet : shellfish, lobster, bacon, turke, beer, ham
STage 1 gout
Asymptomatic hyperuricaemia
No treatment other than lifestyle modifications
Stage 2 gout
Acute gouty arthritis
Acute attack of severe pain, usually in great toe, in early hours of morning and wakes patient
skin is red, hot, shiny, tender
subsides in 3-10 days without treatmetn
Stage 3 gout
Intercritical gout
Time between attacks
Low to no pain
Low level inflammtaion causing joint destruction
Aggressive lifestyle and medication here to prevent chronic gout
Tophi: stone like deposits of monosodium urate in ST, bone, synovium, joints
Stage 4 gout
Chronic tophaceous gout and chronic gouty arthritis
uric acid levels are high over many years
Permanent joint destruction
Diagnosis gout
synovial fluid aspirate
Elevated serum uric acid
X-ray: punched out erosions, tophi and visible joint effusion
Management of gout
NSAIDs acute attack
lifestyle modificatios
corticosteroids for chronic
Allopurinol- xanthine oxidase inhibitor- stops the conversion of xanthine to uric acid
used as prophyalxis and treatmetn
can cause rash, nausea, vomitting, suppress bone marrow
CPPD
calcium phyrophosphate deposition disease
disease of crystal depostion is ST and joits
most common cuase of chondrocalcinosis
main theory is an excess of pyrophosphate production in cartilage which results in calcium pyrophosphate deposition
disease > 65
OA, joint trauma and metabolic disease are risk factors
CPPD clinical features
acute attacks that mimic gout synovitis w tenderness and swelling knee most common, 2nd 3rd MCP, wrist and shoulder fever malaise No joint destruction
Diagnosis of CPPD
Synovial fluid analysys: rhomboid shape rather than rod shaped like gout
X-ray: chondrocalcinosis: hyperwhite line along cartialeg, joint space narrowing, subchondral new bone, no joint destruction
Managment fo CPPD
NSAIDs
Cortisone into joint: prevents further inflammation
oral corticosteroids
