Flashcards in 137 - Monoarthritis/ Gout Deck (44):
inflammatory joint in 1 joint
inflammatory joint pain in 2-4 joints
inflammatory joint pain in >4 joints
what is haemoarthrosis?
bleeding into joint spaces
how woulda patient with monoarthritis present?
pain, hot red and swollen joint, impaired range of movement
what are differential diagnoses for monoarthritis?
septic arthritis, crystal deposition diseases (gout, pseudogout), trauma, other arthritis
what investigations would you carry out for someone suspected with monoathritis?
joint aspiration (gram stain, MC&S, crystallography), Bloods (cultures, FBC for WCC, U&Es for renal function, Inflammatory markers (CRP), X-ray, CXR and KUB (for infection)
Define septic arthritis
invasion of joint by infectious agent producing joint inflammation caused by septicaemia or penetrating injury. Common bacteria: staph aureus, streptococci, gonorrheoa, tuberculosis, Lyme disease, Ecoli (in immunosuppressed)
what are risk factors for septic arthritis?
prosthetic joints, endocarditis, immunosuppression, existing joint damage, IV drug abuse
how does septic arthritis present?
pain, hot red swelling, impaired joint movement, fever, fast onset
how would you treat septic arthritis?
remove the pathogen by needle aspiration or debridement/washout and then IV ABX for 2 weeks and then oral ABX for 4 weeks
What is gout?
arthritis due to the deposition of uric acid crystals. Caused by hyperuricaemia (undersecretion of uric acid or rarely overproduction)
how is uric acid produced in the body?
produced from purine (product of cell breakdown). Adenosine->Iosine->hypoxanthine->xanthine->uric acid. Deposited on damaged cartilage/tendons. WBC attempt to engulf crystals and apoptose causing inflammation
what are the risk factors for gout?
male (30-60), elderly on diuretics, diet (fructose, meat, seafood, alcohol), renal failure, obesity, DM, HTN, heart disease.
How would a patient with gout present?
acute joint pain, swollen tender hot joint, impaired movement, recurrence, MCP joint of big toe, tophi (swelling nodules)
how would you treat gout?
Acute - NSAIDS (contradicted warfarin), colchicine (contradicted renal failure), steroids.
prophylaxis - xanthine oxidase inhibitors (allopurinol, febuxostat), uricosurics (increase uric acid secretion in urine - benzbromarone, sulphinpyrazone, probenecid)
what is pseudogout?
similar to gout but calcium pyrophosphate crystals. Elderly women, knee/wrist, longer attacks, no treatment (analgesia,steroid injection, joint replacement)
what are the two types of focal lesion?
chondral defect - entirely within cartilage, doesnt heal quickly due to no blood supply/stem cell access
osteochondral defect - penetrates to subchondral bone, heals spontaneously as chrondroprogenitor cells invade from blood (usually form fibrocartilage however)
how are cartilage defects classified?`
Grade I - superficial cartilage
Grade II - half the depth of cartilage
Grade III - full depth of cartilage down to subchondral bone
Grade IV - subchondral bone exposure
what are the treatment options for cartilage defects?
Large Defects - total joint arthroplasty
Smaller defects - debridement (frayed edges removed to reduce friction/inflammation), microfracture (punctures in subchondral bone to bleed and supply stem cells - usually fibrocartilage formed), osteotomy (wedge of bone removed to remove deformity), osteochondral grafting, autologous chondrocyte implantation (chondrocytes grown and sealed with periosteal flap.
what happens in osteoarthritis?
cartilage degradation/proteoglycan loss, surface fibrillation, loss of metachromasia (staining), chondrocyte clustering , chondrocyte apoptosis, hyperplasia of synovium
what is the purpose of calcium homeostasis?
to maintain a constant blood calcium concentration through organ systems (gut bone kidney) and hormones (PTH, vitD3, calcitonin)
what are the functions of calcium in the body?
formation of calcified tissue (bone and teeth), normal activity of nerve and muscle, action potentials & excitation contraction coupling, stimulate release of neurotransmitters hormones & glandular secretions, maintenance of cell membrane integrity/permeability, cell adhesion, blood clotting
what are the influxes and effluxes of calcium in the body/
influxes - skeleton (reservoir - incr. absorption when levels low), diet (0.2g absorbed daily (intake 1g daily - 0.8g in faeces) - increase absorption when levels low)
effluxes - 0.2g excreted daily in urine
how is calcium bound in the blood?
45% bound to proteins, 10% to inorganic ions, 45% free in blood (ionised) which is sensed by PTH
where is PTH produced, where is it secreted and how does act when blood calcium is low?
produced in chief cells of parathyroid glands, secreted when blood calcium is low by calcium sensing receptors. Causes incr. intestinal absorption via 1,25(OH)2D3 (PTH stimulates formation), incr. resorption from bone (stimulates osteolysis & incr. osteoclasr activity), decr. excretion (incr. renal absorption in DCT and decr. PO4 reabsorption)
how is DHCCF (1,25(OH)2D3) produced and how does it act when blood calcium is low?
sterol 7-dyhydrocholesterol in skin with UV light->vitD3->liver->25(OH)D3->kidneys (accelerated by PTH) ->1,25(OH)2D3
Causes incr. absorption in intestines (Ca pump), incr. renal absorption (binding proteins in DCT), incr. bone resorption (incr. osteoclast development), decr. PTH production (-ve feedback)
where is calcitonin produced and how does it act when blood calcium is high?
produced by c cells in thyroid (parafollicular cells). Responds to high calcium in blood and causes: inhibits resorption (inhibits osteoclasts)
what are two vit D deficiency pathologies/
rickets in children - insufficient bone mineralisation, bowing of growing long bones and easy fracture
osteomalacia in adults - incr. unmineralised ostroids and decr. bone strength (fractures)
why is drug metabolism important?
It makes drugs more hydrophilic for excretion by the kidneys and inactivates the drug so that it no longer produces an effect. Major site for transformation is the liver (cytochrome P450). Also the GIT (monoamine oxidase).
what is 1st pass metabolism?
hepatic portal vein takes blood from the GIT through the liver into systemic circulation ie this is the way oral drugs are metabolised not IV drugs
what are phase 1 reactions?
reactions to convert lipophilic drugs into more water soluble drugs by introducing/masking functional groups, oxidation, reduction and hydrolysis.
what are phase 2 reactions?
conjugation reactions adding large endogenous molecules to drugs to make them more water soluble by glucoroidation, sulphation, methylation, acytylation
what is 1st order pharmacokinetics?
drugs metabolised by enzymes at a rate below michaelis' constant
rate of drug metabolism v = vmax [C] / km + [C]
what is zero order pharmacokinetics?
this is non linear pharmacokinetics. drugs are administered at concentrations well above michaeli' constant and binding sites on enzymes are saturated.
v = vmax [C] / [C] = vmax
what is enzyme competition and how does it affect drug metabolism?
some drugs are metabolised by the same enzyme and compete for the same active site causing a reduction in metabolism of both drugs and an incr. plasma concentration. This is called pharmacokinetic drug interaction
what is induction of metabolism?
certain drugs induce enzymes to incr. their own metabolism
what is the inhibition of enzymes?
certain drugs inhibit enzymes to incr. their own concentration in the plasma
what are pro-drugs?
drugs administered in an inactive form
what are the common routes of drug elimination?
renal (most common), lungs (inhaled drugs & alcohol), bile (goes to GIT - prolonged effect), intestines (faeces -incr. speed of transit = incr. elimmination), secretions (sweat, saliva, milk for more lipid soluble drugs)
how are drugs eliminated by the kidneys?
only free drugs in the plasma. Go to renal glomerulus->active secretion->passive reabsorption of lipid soluble drugs->excretion of water soluble drugs
what is drug clearance?
volume of plasma containing the total amount of drug that is removed from the body in unit time
CL = renal plasma flow x extraction ratio (decline on drug conc. from arterial to venous side of kidney)
what is the elimination half life and how can it be affected?
time taken for the body to eliminate half the dose of a drug. Reduced GFR can lead to slow removal, hepatic impairment reduces metabolism, incr. adipose mass. Also less efficient in young and old as GFR is reduced and very young have less metabolising enzymes