137 - Monoarthritis/ Gout

Question 0

define oligoarthritis

Answer 0

inflammatory joint pain in 2-4 joints

Question 1

Define monoarthritis

Answer 1

inflammatory joint in 1 joint

Question 2

define polyarthritis

Answer 2

inflammatory joint pain in >4 joints

Question 3

what is haemoarthrosis?

Answer 3

bleeding into joint spaces

Question 4

how woulda patient with monoarthritis present?

Answer 4

pain, hot red and swollen joint, impaired range of movement

Question 5

what are differential diagnoses for monoarthritis?

Answer 5

septic arthritis, crystal deposition diseases (gout, pseudogout), trauma, other arthritis

Question 6

what investigations would you carry out for someone suspected with monoathritis?

Answer 6

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)

Question 7

Define septic arthritis

Answer 7

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)

Question 8

what are risk factors for septic arthritis?

Answer 8

prosthetic joints, endocarditis, immunosuppression, existing joint damage, IV drug abuse

Question 9

how does septic arthritis present?

Answer 9

pain, hot red swelling, impaired joint movement, fever, fast onset

Question 10

how would you treat septic arthritis?

Answer 10

remove the pathogen by needle aspiration or debridement/washout and then IV ABX for 2 weeks and then oral ABX for 4 weeks

Question 11

What is gout?

Answer 11

arthritis due to the deposition of uric acid crystals. Caused by hyperuricaemia (undersecretion of uric acid or rarely overproduction)

Question 12

how is uric acid produced in the body?

Answer 12

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

Question 13

what are the risk factors for gout?

Answer 13

male (30-60), elderly on diuretics, diet (fructose, meat, seafood, alcohol), renal failure, obesity, DM, HTN, heart disease.

Question 14

How would a patient with gout present?

Answer 14

acute joint pain, swollen tender hot joint, impaired movement, recurrence, MCP joint of big toe, tophi (swelling nodules)

Question 15

how would you treat gout?

Answer 15

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)

Question 16

what is pseudogout?

Answer 16

similar to gout but calcium pyrophosphate crystals. Elderly women, knee/wrist, longer attacks, no treatment (analgesia,steroid injection, joint replacement)

Question 17

what are the two types of focal lesion?

Answer 17

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)

Question 18

how are cartilage defects classified?`

Answer 18

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

Question 19

what are the treatment options for cartilage defects?

Answer 19

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.

Question 20

what happens in osteoarthritis?

Answer 20

cartilage degradation/proteoglycan loss, surface fibrillation, loss of metachromasia (staining), chondrocyte clustering , chondrocyte apoptosis, hyperplasia of synovium

Question 21

what is the purpose of calcium homeostasis?

Answer 21

to maintain a constant blood calcium concentration through organ systems (gut bone kidney) and hormones (PTH, vitD3, calcitonin)

Question 22

what are the functions of calcium in the body?

Answer 22

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

Question 23

what are the influxes and effluxes of calcium in the body/

Answer 23

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

Question 24

how is calcium bound in the blood?

Answer 24

45% bound to proteins, 10% to inorganic ions, 45% free in blood (ionised) which is sensed by PTH

Question 25

where is PTH produced, where is it secreted and how does act when blood calcium is low?

Answer 25

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)

Question 26

how is DHCCF (1,25(OH)2D3) produced and how does it act when blood calcium is low?

Answer 26

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)

Question 27

where is calcitonin produced and how does it act when blood calcium is high?

Answer 27

produced by c cells in thyroid (parafollicular cells). Responds to high calcium in blood and causes: inhibits resorption (inhibits osteoclasts)

Question 28

what are two vit D deficiency pathologies/

Answer 28

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)

Question 29

why is drug metabolism important?

Answer 29

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).

Question 30

what is 1st pass metabolism?

Answer 30

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

Question 31

what are phase 1 reactions?

Answer 31

reactions to convert lipophilic drugs into more water soluble drugs by introducing/masking functional groups, oxidation, reduction and hydrolysis.

Question 32

what are phase 2 reactions?

Answer 32

conjugation reactions adding large endogenous molecules to drugs to make them more water soluble by glucoroidation, sulphation, methylation, acytylation

Question 33

what is 1st order pharmacokinetics?

Answer 33

drugs metabolised by enzymes at a rate below michaelis’ constant
rate of drug metabolism v = vmax [C] / km + [C]

Question 34

what is zero order pharmacokinetics?

Answer 34

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

Question 35

what is enzyme competition and how does it affect drug metabolism?

Answer 35

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

Question 36

what is induction of metabolism?

Answer 36

certain drugs induce enzymes to incr. their own metabolism

Question 37

what is the inhibition of enzymes?

Answer 37

certain drugs inhibit enzymes to incr. their own concentration in the plasma

Question 38

what are pro-drugs?

Answer 38

drugs administered in an inactive form

Question 39

what are the common routes of drug elimination?

Answer 39

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)

Question 40

how are drugs eliminated by the kidneys?

Answer 40

only free drugs in the plasma. Go to renal glomerulus->active secretion->passive reabsorption of lipid soluble drugs->excretion of water soluble drugs

Question 41

what is drug clearance?

Answer 41

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)

Question 42

what is the elimination half life and how can it be affected?

Answer 42

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

Question 43

what is a loading dose?

Answer 43

large first dose to reach a certain plasma concentration and then smaller doses to maintain level