MSK Exam 1 Flashcards
yellow marrow is where
medullary cavity of diaphysis of long bones
red marrow is where
spaces in epiphyses and other spongey bone
hematopoiesis
organic bone matrix
1/3 bone weight
type I collagen
tensile strength
also osteonectin, ossteopontin, proteoglycans, gammacarboxyglutamic acid
inorganic mineral salts
2/3 bone weight
mainly calcium phosphate as crystals called hydroxyapatite
gives hardness and compressional strength
also amorphous calcium phosphates
pyrophosphate does whate
prevent calcium phosphate crystalization in extracellular tissues
osteopbalsts
bone forming cell
produce collagen 1, osteocalcin, osteopontin
-tissue nonspecific alkaline phosphatase on surface breaks pyrophosphate so calcification can occur
-produces nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) and ankylosis protein (ANK) to make pyrophosphate available
-PTH and vit D receptors to regulate RANKL, OPG, MCSF1
osteocyte
remain in cortical bone during remodeling
-permits translocation mineral in and out of remodeling regions
-mechanical sensors provide signals for remodeling
-produce factors modulating distant tissue function (FGF23 affects phosphate excretion and vit d metabolism)
osteoclast
multinucleated giant cells for bone resorption
after sealing area develop invaginated structures culled ruffled border which acts as lysosome (secretes acid and proteases like cathepsin K)
-controlled by number of osteoclasts (macrophage colony stimulating factor 1) and osteoclast activity (PTH, vit d through induction of RANKL)
endochondral ossification
at epiphyseal plate
cartilage mold develops
cartilage converted to bone (as plate widens part next to diaphysis becomes bone)
epiphyseal plate ossifies near end of puberty to end growth
formation of bone
osteoblast secretes collagen and ground substance
colagen forms osteoid and entraps osteoblasts to form osteocytes
calcium salts precipitate and form hydroxyapatite crystallization
importance of bone remodeling
-old bone becomes brittle and weak
-adjust strength in proportion to bone stress
-adjust for mechanical forces in accordance with stress patterns
bone remodeling
complete cycle may take 6 months
-physical or biochemical signals precursor osteoclasts from bone marrow to specific loci on bone
-form osteoclasts which cut tunel through bone
-osteoblasts reverse tunnels to new bone
remodeling trabecular bone
osteoclast digs cavity
osteoblasts recruited to base
calcification occurs
bone returns to quiescent state
hormonal control bone resorption
-PTH binds osteoblasts which secrete RANKL and MCSF1 (bind preosteoclasts), preosteoclasts form into osteoclasts and activity stimulated by RANKL, osteoclasts for ruffled border and release enzymes and acids
-osteoblasts secrete osteoprotegrin (OPG) which is decoy for RANKL, low OPG/RANKL ratio increases osteoclast formation and activity
-RANKL stimulated by vit d, pth, pthrp, il11, il6, il1, glucocorticoids
-estrodiol promotes OPG
factors for bone deposition
compression load - greater compression greater bone deposition
bone shape - altered with increased deposition
rate of fracture repair - depends whether use maintained or immobilized, fracture plates
dietary availability calcium
increased osteoclast activity in
hyperparathyroidism
hyperthyroidism
hypervitaminosis D
hypogonadism (postmenopause)
pagets disease
-increased osteoclast activity causes -increased osteoblast activity
-irregular bone formation - disorganized
-increased density in some areas but still weak
growth hormones
increase bone remodeling
stimulate cartilage growth
sex steroids
testosterone and estradiol promote osteoblast activity
glucocorticoids
increase RANKL, inhibit OPG, increase osteoclasts
deplete osteoblasts by inhibiting replication precursors
suppress gonadotropin causing hypogonadal state
increased renal calcium loss and intestinal calcium loss cause increased PTH
estrogen
activates osteoblasts and secretion of OPG
decrease in postmenopause causes bone resorption to be greater then deposition so lose bone mass
Salter Harris classification
1 - S: separation through physis (degenerating cartilage cells)
2 - A: above physis
3 - L: lower than physis
4 - TE: through everything
5 - R: cRushed physis
anterior shoulder dislocation
axillary nerve injury
closed reduction, immobilization, PT
posterior shoulder dislocation
seizures and electrocutions
proximal humerous fracture
usually surgical neck
elderly/osteoporosis: FOOSH injury
young: high energy trauma
axillary nerve damage
open reduction with internal fixation
humeral shaft fracture
direct blow/fall/MVA
radial nerve injury - wrist drop and loss of sensation posterior arm/forearm/dorsal hand
joint effusion after trauma
displaced fat pad (seen posterior)
sail sign
kids - supracondylar fracture
adults - radial head fracture
supracondylar fracture
FOOSH
might not see on xray look for posterior fat pad
median nerve injury
little leaguers elbow
medial elbow pain
stress/avulsion fracture medial epicondyle
injury to ulnar collateral ligament
golfers elbow
medial epicondylitis
repetitive flexion
tennis elbow
lateral epicondylitis
repeated extension
MRI preferred
nursemaid elbow
radial head subluxation
pulling arm or swingin by arm
monteggia fracture dislocation
ulna shaft fracture with radial head dislocation
FOOSH
galeazzi fracture dislocation
radius fracture and distal radioulnar dislocation
FOOSH usually children
colles fracture
distal radius fracture with dorsal displacement of distal fracture fragments and wrist
usually extraarticular
FOOSH, high energy trauma in young, osteoporotic and older patients common
dinner fork appearance
scaphoid fracture
lunar lucency through scaphoid
FOOSH
pain and swelling at base of thumb
risk of avascular necrosis and non union
AVN risk
CASTS Bend LEGS
C - corticosteroids
A - alcoholism
S - sickle cell anemia
T - trauma
S - SLE
Bends
Le - Legg Calve Perthes
G - gaucher disease
S - slipped capital femoral epiphysis
wrist dislocation
lunate
“spilled teacup”
can have median nerve injury
FOOSH/acute forceful dorsiflexion
rotator cuff tear
microtrauma/degeneration
acute traumatic episode
pain, weakness, decreased ROM, clicking, catching, stiffness, crepitus
osteoporosis
bone loss leaves bone fragile and with high risk of fracture
<-2.5
can have little to no clinical symptoms (ab 2/3 vertebral fractures asymptomatic)
dx by low bone mineral density of fragility fracture or combo of the 2 with elevated FRAX
ptimary - iodopathic, postmenopausal, senile
secondary - extrinsic cause (endocrine, GI, drugs)
osteopenia
reduction in bone mass
<-1 to >-2.5
DXA scan scores
T score - against young adult population
Z score - aged matched controls
early screening if
low body weight
- young female athlete triad (amenorrhea aka no period, poor diet, osteoporosis especially if steroid use)
recommend screening if
increased thoracic kyphosis (suspect vertebral compression fracture)
osteoarthritis
degenerative joint disease - destruction and erosion of articular cartilage
most commonly weight bearing joints
usually asymmetric
progressive and irreversible
involves whole joint
primary - no identifiable predisposing conditions
secondary - underlying cause (trauma, deformity, systemic disorder)
-symptoms: evening and morning stiffness common, pain in ROM, crepitus, osteophytes/bone spurs, swelling, joint space narrowing, subchondral sclerosis, subchondral cyst
-tx: lifestyle and activity modification, massage/OMT, NSAIDs, glucocoricoid/hyaluronic acid injections, joint replacement sx
-risk factors: older than 60, women (hand/knee), joint injury or trauma, joint shape, obesity, genetics
calcium balance
extracellular calcium is what is regulated
3 tissues: GI, bone, kidney
-acidosis = increased Ca
-alkalosis = decreased Ca
phosphate
85% stored in bones
found as alkaline phosphate and acidic phosphate
binds protein
imbalances fixed with calcium regulation
calcium and phospate together because
both are components of hydroxyapatite crystals
both regulated to prevent matastatic calcification
regulated by PTH, vit d.calcitriol, fgf23, calcitonin
parathyroid hormone (PTH)
senses extracellular calcium through calcium sensing receptor (CaSR)
-decrease in Ca stimulates PTH secretion
-increased phosphate stimulates PTH secretion
-vit d inhibits PTH secretion
-conditions that increase Ca decrease PTH secretion: increased dietary calcium and vit d, bone resorption from other causes than PTH
-renal : increase Ca reabsorption, reduce phosphate reabsorption, stimulate vit d activation, inhibit Na H exchangers decreasing HCO3 absorption (mild hyperchloremic acidosis)
-GI : effects indirect through activation of vit d which increases renal calcium reabsorption, increases absorption of Ca and phosphate in small intestine, modulates mvmt Ca and phosphate from bone
-bone : stimulate resorption of calcium (through secretion of RANKL from osteopblasts that have PTHR), stimulate osteoblasts to secrete MCSF1 to differentiate osteoclast precursors
PTH related peptide (PTHrP)
synthesized in abnormal cells or malignant tumors (also lactating breast)
mimics PTH in bone and kidney, but affects tend to be localized
vitamin d
active metabolite is 1,25-dihydroxyvitamin D
large store in fat
-small intestine : enhance calcium and phosphate absorption
-kidney : enhance calcium and phosphate absorption
-bone : increases bone resorption, promote bone formation if adequate Ca available
vitamin D deficiency
rickets - children, bowing bones (abnormal amounts unmineralized bone)
osteomalacia - adults (usually impaired absorption vit d and calcium), cause hypocalcemia/osteoporosis/secondary hypoparathyroidism, abnormal amounts unmineralized osteoid
calcitonin
synthesized in C cells of thyroid
use CaSR
-high Ca increases calcitonin to reduce blood calcium (increased bone deposition, decreased resorption from kidney)
may affect children more
tumor marker for medullary carcinoma of thyroid
therapeutic as inhibitor of osteoclass in Paget disease
Fibroblast Derived Growth Factor 23 (FGF23)
secreted by osteocytes bc elevated phosphate/calcitriol/PTH
-decrease formation 1,25-dihydroxyvit D
-increase renal secretion of phosphate (reduce insertion NaPi-Ila in kidney)
hypocalcemia
nerves more sensitive to depolarization (sense tingling/numbness, motor has spontaneous muscle contraction)
-bone resorption increases
hypercalcemia
decreases neuronal excitability
-caused by increased bone resorption, increased GI absorption, decreased renal excretion
-central defense is suppression of PTH
primary hyperparathyroidism
increased release of PTH
-hypercalcemia, hypophosphatemia, increased bone resorption, increased phosphate excretion, increased renal calcium reabsorption
secondary hyperparathyroidism
high PTH due to low calcium
-caused by vit d deficiency, chronic renal disease
hypoparathyroidism
decreased PTH
common result of thyroid surgery or congenital disorders
-hypocalcemia, hyperphosphatemia, decreased phosphate excretion, signs of tetany
pseudohypoparathyroidism
end organ resistance to PTH due to defect PTH receptor in kidney and bone
-hypocalcemia, hyperphosphatemia, increased PTH levels
familial hypocalcuric hypercalcemia
loss of function of CaSR, decreased sensitivity of Ca causes hypercalcemia
usually asymptomatic
osteopetrosis
decreased osteoclast resorption with theck but weak bone
mucopolysacharidosis
defects in lysosomal enzymes that degrade chondrocytes and affect hyalin cartilage
disorders with curvature
kyphosis, lordosis, scoliosis
cause pain, deformations, restrictive lung disease
ehler danlos
defects in synthesis or structure of fibrillar collagen
-joint laxity with hypermobility
-hyperextensible and thin skin
-rupture of internal organs
-rupture of cornea and retinal detachment
marfan syndrome
defects in extracellular glycoprotein fibrillin 1
-long tapering digits
-hypermobile joints
-vertebral, facial, chest abnormalities
-subluxation and dislocation of lens
-cystic medial necrosis of aortic wallF
FGFR3 mutations
overactive FGFR3 and decreased endochondral ossification
-achondroplasia : short limbed dwarfism with retarded endochondral ossification
-thanatophoric dwarfism : effects greater, death early in life
osteogenesis imperfecta
deficient syntheis type I collagen
type II is perinatal lethal form
renal osteodystrophy
bone disease secondary to renal dysfunction
-decreased vit d causing secondary hypoparathyroidism
Antiabsorptive agents for osteoporosis
Bisphosphonates
Denosumab
Romosuzumab
Selective estrogen receptor modulators (raloxifene)
Calcitonin
Anabolic agents for osteoporosis
Intermittent PTH
Teriparatide
Abaloparatide
Bisphosphonates
Decrease fracture risk by 50%, first line therapy
Etidronate
Alendronate
Pamidronate
Risedronate
Tiludronate
Zoledronic Acid (IV)
Inhibit farnesyl pyrophosphate synthase
Vitamin D production
Calcium absorption from GI
Gastric and esophageal irritation, food impair absorption
Strontium
Divalent cation, resembles calcium
Agonize calcium sensing receptor enhancing osteoblasts and suppressing osteoclasts
DO NOT USE IN PHENYLKETONURIA
Teriparatide
Synthetic PTH
Stimulates osteoblasts, GI absorption calcium
Low intermittent dosing
Can cause hypercalcemia
Abaloparatide basically the same just different AAs
Denosumab
Human monoclonal antibody binds and prevent action RANKL
Inhibit osteoclasts formation
SubQ every 6 months
Romosozumab
Sclerostin inhibitor which is produce by osteocytes and prevents bone formation
BBW cardiovascular accidents
SERMs
Enhance spinal bone mass
Decrease vertebral fractures
Does not prevent hip fractures
Calcitonin
Minor spinal fracture protection
No protection against nonvertebral fractures
Nasal spray
Inhibits bone resorption
Diuretics and calcium
Loop - increase urine calcium
Thiazides - decrease urine calcium
Kidney disease
Deficiency in calcitriol
Phosphate retention and reduced calcium
Secondary hyperparathyroidism
FGF23 levels increase bc increased phosphate
Hypocalcema
Tx - vitamin D analogs, calcitriol, doxercalciferol/paricalcitol to combat hyperparathyroidism (suppress PTH and less risk hypercalcemia), cinacalcet/etecalcitide (activate calcium sensing receptor in parathyroid cells)
bone tumors
benign - osteoma, osteoid osteoma, osteoblastoma
malignant - osteosarcoma
osteoma
sessile, middle aged
projection from subperiostal surface
woven and lamellar bone - skull/facial
gardner syndrome - multiple (FAP mutations with intestinal polyps, epidermal cysts, other tumors)
symptoms due to location or size
osteoid osteoma
first two decades, usually men
painful, wake from sleeping, resolved by aspirin
central nidus of irregular well vascularized osteoid and woven bone surrounded by shell of sclerotic bone
osteoblastoma
does not have nocturnal pain, larger, occurs in posterior spine
tx - sx or radiofrequency ablation
malignant transformation when treated with radiation
no sclerotic rim
osteosarcoma
metaphysis of long bones, mostly males, teenagers and young adults
associated with fibrous dysplasia and osteomyelitis
increased risk with inherited retinoblastoma loss, Li fraumeni (p53), also INK4A/p14 or p16 abnormalities
formation of osteoid by spindle shaped malignant cells
lifts periosteum (codman triangle)
very aggressive
tx - resection and chemo (limb sparing sx)
cartilage forming tumors
benign - chondroma, chondroblastoma, osteochondroma, chondromyxoid fibroma
malignant - chondrosarcoma
chondroma
solitary, small bones of hands/feet
enchondroma - within medullary cavity
periosteal/juxtacortical - on surface
multiple enchondromas bc ollier or maffucci (increased risk malignancy)
doesnt expand, erode, or cause pain
proliferation of mature hyalin cartilage
tx - observation and curettage
osteochondroma
exocytosis - projection of cartilagenous growth plate
most solitary and on long bones, composed of bony stalk capped by cartilage (mushroom)
late adolescents/early adulthood, men»_space;» women
multiple may be part of osteochondromatosis (EXT1 or EXT2 gene)
can impinge peripheral nerves
chondrosarcoma
broad age range, some in conjunction with enchondromatosis or osteochondromatosis
more men
can occur in paget disease
expand bone, erode cortex, produce pain
lower grade, less aggressive, slower growing, less likely to metastasize (if do its to lung or skeleton)
tx - sx resection
fibrous or fibro-osseous like tumors
benign - fibrous cortical defect, nonossifying fibroma, fibrous dysplasia
fibrous dysplasia
abnormal persistence of fibrous tissue in bone, bone arises in it, ocasionally have cartilage within
common in skull, ribs, jaws, femur
x ray has hazy ground glass quality
may thin bone cortex with bowing (shepherds crook)
associated with constitutive activation of adenyl cyclase
(alphabet soup appearance)
mccune albright syndrome - polyostotic fibrous dysplasia, cafe au lait spots, endocrinopathies
non-ossifying fibroma/fibrous cortical defect
fibrous cortical defect is smaller, non-ossifying fibroma is larger but they are the same pathologies
in metaphysis of long bones
composed of fibroblasts (pinwheel pattern) and macrophages (can be multinucleated)
pathologic fractures
tx - curettage
notochord tumors
malignant - chordoma
chordoma
derived from remnants of embryonic notochord
uncommon under 40, metastases rare
common in sacrococcal regionand sphenooccipital region
large vacuolated cells surrounded by abundant intercellular matrix
grow slowly but grow in bone and difficult to excise completely, radiation therapy also used
other tumors of skeleton
benign - giant cell tumor, aneurysmal bone cyst
malignant - ewing sarcoma/PNET, metastases
ewing sarcoma
children and teenagers
in diaphysis of long bones
small round blue cell tumor
PAS staining shows glycogen, RANKL expressed
primitive neuroectoderm tumor - has t(11;22) with fusion EWS-FLI1 gene that produces active transcription factor
very aggressive and destructive, local pain and fever
often metastasize to lung
tx - chemo, sx, radiation
may arise primarily in soft tissue
giant cell tumor (osteoclastoma)
osteoblast derived small mononuclear cells that stimulate osteoclast differentiation and proliferation via RANKL
tx - curettage and sclerosis of residual cavity
malignant if radiation
age 20-40
“soap bubble” in epiphysis of long bones
giant cells with many nuclei
aneurysmal bone cyst
deforms bone in aneurysmal fashion, metaphyseal location
produces pain and swelling
may occur on top of another bone tumor
hemorrhagic cysts with giant cells and cellular fibroblastic tissue with surrounding eggshell of new woven bone
frequently in first 2 decades
17p13 translocation causing upregulation of USP6
tx - curettage
metastatic bone tumors
most adenocarcinomas (lead kettle) - Prostate, Breast, Kidney, Thyroid, Lung
blastic, lytic or mixed
usually over 40
metastatic sites axial skeleton and proximal femur
adipose tumors
benign - lipoma
malignant - liposarcoma
lipoma
composed of mature adipocytes
mostly soft, mobile, painless
cured by local excision
liposarcoma
50-60
genetic defects - amplification of chromosome 12 (MDM2 which is an inhibitor of p53)
subtypes - pleiomorphic usually aggressive and frequent metastasizes
fibrous tumors
benign - nodular fascilitis, deep fibromatosis, superficial fibromatosis
malignant - fibrosarcoma
nodular fascitis
self limited composed of fibroblasts nd myofibroblasts
can follow trauma
superficial fibromatosis
fibroblastic proliferation
palmar (dupuytren) - flexion contractions in hand
penile (peyronie) - palpable mass on penis that results in abnormal curvature with possible contraction of urethra
deep fibromatosis
desmoid tumors
large infiltrative masses that recur but do not metastasize
teens to 30s especially women
can have mutation in APC or beta catenin or part of familial adenomatous polyposis (Gardner syndrome)
fibrosarcoma
now considered synovial sarcomas or undifferentiated pleomorphic sarcomas
herringbone pattern
skeletal muscle tumors
benign - rhabdomyoma
malignant - rhabdomyosarcoma
rhabdomyoma
seen with tuberous sclerosis
cardiac tumors in children
rhabdomyosarcoma
alveolar - resemble lung tissue (usually children and adolescents), common in head/neck/GU
embryonal - common in children and adolescents, sarcoma botyroides (best prognosis) resembles grapes and occurs beneath mucous membranes of hollow organs
pleiomorphic - adults, worst prognosis
smooth muscle tumors
benign - leiomyoma
malignant - leiomyosarcoma
leiomyoma
fibroid
common in uterus
associated with renal cell carcinoma
spindle cells with few mitoses
leiomyosarcoma
in extremities and retroperitoneum (tend to be bulky and metastasize to lungs)
increased mitotic figures
immunohistochemical markers for actin and desmin
joint tumors
benign - ganglion, synovial cyst, tenosynovial giant cell tumor
ganglion cyst
cystic nodule near joint capsule or tendon sheath - most common in wrist
from myxoid or cystic degeneration of connective tissue (no cellular lining)
fluid in cyst similar to synovial fluid, no communication with joint space
synovial cyst
herniation of synovium or enlargement of bursa
synovial lining hyperplastic and contain inflammatory cells and fibrin
tenosynovial giant cell tumor
several neoplasms that develop in synovial lining of joints, tendon sheaths, bursae
intra or extra articular
diffuse type - pigmented villonodular synovitis affecting large joints
localized type - discrete nodule attached to tendon sheath
mutations in overexpression M-CSF and proliferation of macrophages
uncertain origin soft tissue tumors
malignant - synovial sarcoma, undifferentiated pleiomorphic sarcoma
synovial sarcoma
doesnt arise from synoviocytes, occurs in locations outside joints
biphasic with epithelial and spindle cells
undifferentiated pleomorphic sarcoma
undifferentiated, high grade, pleomorphic
deep soft tissue of adults (especially thigh)
malignant fibrous histiocytoma in past
poor prognosis
non-opioid analgesics
salycilic acid derivatives - acetylsalysilic acid, sodium salicylate, mesalamine
oxicams - meloxicam, piroxicam
propionic acid derivatives - ibuprofen, naproxen
indole derivatives - indomethacin, sulindac
acetic acid derivatives - diclofenac, ketorolac
selective cox 2 inhibitor - celecoxib
anagesic/antipyretic - acetaminophen (acetylcysteine for acetaminophen toxicity)
nsaids properties
antipyretic, analgesic, anti inflammatory
-non aspirin has BBW for increased risk cardiovascular accidents
-aspirin has antiplatelet activity to prevent MI and stroke
-all have BBW for GI adverse effects
-other warnings are kidney dysfunction, bleeding risk, fluid retention, not recommended in pregnancy
acetominophen
works in CNS, antipyretic and analgesic, not antiinflammatory
liver toxicity
NSAID MOA
block COX to inhibit prostoglandin and thromboxane biosynthesis
-nonaspirin : reversible competitive inhibition
-aspirin : irreversible inhibition
celecoxib
selective COX 2 inhibitor (reduced GI side effects)
risk of prothrombotic effects
lower risk of bleeding
cross reactivity with sulfa allergy
short acting NSAIDs
ibuprofen, diclofenac, indomethacin
long acting NSAIDs
naproxen, celcoxib, meloxicam, piroxicam
ketorolac
++analgesic
oral, IV, IM, ophthalmic eye irritation
increased GI risk and bleeding risk (peptic ulceration and renal compromise common)
max 5 days
not recommended in children
diclofenac
++ anti inflammatory
acute musculoskeletal pain and long term treatment (RA, OA, AS)
oral, ophthalmic, gel on top of joint (less systemic side effects)
meloxican
preferentially inhibits COX2 and inhibits COX1
oral once daily for maintenance OA/RA
better tolerated than piroxicam
piroxicam
++anti inflammatory
oral once daily
higher GI toxicity and phototoxic cutaneous eruptions
indomethacin
acute gout, OA, RA, bursitis, tendinitis
+++ anti inflammatory
potent inhibitor of COX, phospholipase A, PMNs cell migration, T and B cell differentiation
with ibuprofen for patent ductus arteriosus closure in neonates
sulinfac
not common
less potent and less adverse effects than indomethacin
ibuprofen and naproxen
OTC, less GI toxicity hen taken appropriately
PRN for pain, inflammation, fever
2 hr half life
aspirin
antiplatelet (through thrombocane A2 which is a platelet aggregator) and anti inflammatory
more frequent doses for anti inflammatory action
GI effects, tinnitis, high dose causes respiratory alkalosis, low dose causes acidosis, dilates blood vessels and increases blood volume, inhibit renal uric acid excretion
reyes syndrome
do not use aspirin for pediatric patients recovering from chickenpox or flu
causes cerebral edema and fatty infiltration of liver and other organs
vomiting, sudden change in mental status
salycilate toxicity
tinnitus, nausea/vomiting, tachypnea, hyperpnea, hyperthermia, tachycardia
tx - supportive care, activated charcoal, alkalinize with sodium bicarbonate IV
acetominophen
paraminophenol derivative, acts on CNS via COX inhibition
analgesic and antipyretic, not antiinflammatory
liver toxicity
acetylcysteine for overdose bc it replenishes hepatic stores of gluthione
gout
high blood levels of uric acid (hyperuricemia)
caused by overproduction or underexcretion
arthritis, urinary calliculi, sodium urate crystals in joints, cartilage, and kidneys
sudden pain in single joint
acute gout treatment
anti-inflammatory agent
-NSAIDs, colchicine, systemic corticosterois
aspirin contraindicated bc inhibits uric acid secretion
chronic gout treatment
allopurinol
febuxostat
probenecid
under excretors
increase renal excretion of uric acid
probenecid
use when on meds that increase uric acid (thiazide diuretics or niacin)
over producers
inhibit uric acid synthesis
allopurinol - competitive xanthine oxidase inhibitor
febuxostat - nonpurine xanthine oxidase inhibitor
opioid agonists
full (strong) - morphine, meperidine, oxymorphone, hydromorphone, methadone, fentanyl, heroin
full (moderate) - codeine, hydrocodone, oxycodone
full (weak) - diphenozylate and atropine, loperamide
partial/mixed agonists - buprenorphine, butorphanol, nalbuphine, pantazocine
other - tramadol, tapentadol, dextromethorphan
opioid antagonists
central - naloxone, nalmefene, naltrexone
partial - methylnaltrexone, naloxegol, alvimopan
opioid dependence MOA
persistent activation of Mu receptors cause decrease in receptor cycling and receptor uncoupling with intracellular targets
steps for pain management
- non opioid analgesic - acetominophen, cox 2 inhibitors (celecoxib) and aspirin, NSAIDs (ibuprofen, naproxen, ketorolac, diclofenac, nabumetone)
-patients who fail 1st step should get non opioid analgesic and oral immediate acting opioid (hydrocodone/APAP or tramadol) - short acting opioid for moderate pain - codeine (usually w/ NSAID or acetominophen), tramadol (combined w/ acetaminophen or alone), hydrocodone (with acetominophen/aspirin/ibuprofen), oxycodone (combined with acetaminophen/aspirin/ibuprofen), meperidine (contraindicated using MAO inhibitors)
- short acting opioid for moderate to severe pain - morphine, hydromorphone, meperidine (not cancer), oxycodone, oral fentanyl, buprenorphone (can cause withdrawal), butorphanol and nalbuphine (no oral formulation, can cause withdrawal), pentazocine
- long acting opioidds for moderate to severe pain - methadone, fentanyl patch, modified morphine/oxycodone/oxymorphone
opioid mechanism of action
bind mu opioid receptors
ascending pathway - close voltage gated Ca channels on presynaptic terminals, open K channels in postsynaptic neurons (block signal from dorsal horn)
descending pathway - inhibit GABA neurons causing activation of descending inhibitory neurons
glucuronidation
hydromorphone, levorphanol, oxymorphone
CYP metabolism
codeine, oxycodone, meperidine, fentanyl, alfentanil, methadone
drug interactions
benzos!!!!
antipsychotic tranquilizers
MAO inhibitors
meperidine
anticholinergic effects
cause pupils to dilate not constrict
serotonergic
CNS excitation at high doses
long half life
tramadol
increased risk of seizures
blocks NE uptake
serotonin syndrome
dextromethorphan
decrease sensitivity of cough receptors through sigma receptor stimulation
overdose and constipation common
septic arthritis
infection within the joint
adults and adolescents - n gonorrhea, s aureus, streptococci
neonates - group B strep, escherichia coli, staph aureus
less than 3 - strep pyrogenes, strep pneumoniae, staph aureus
3 to adolescent - staph aureus, n gonorrhea, p. aeruginosa
osteomyelitis
infection of bone marrow
staph aureus leading cause
other coagulase negative staph/strep, gram neg bacilli (e coli, pseudomonas spp.)
neisseria gonorrhea
gram negative diplococci
aerobes but require increaed CO2
chocolate agar and thayer martin agar
use dacron or rayon swabs
oxidase positive
no maltose fermentation, no capsule
virulence fators - pili, outer membrane proteins, lipooligosaccharides, peptidoglycan, IgAse
staphylococcus
gram positive cocci
catalase positive
aureus - coagulase positive, beta hemolysis
epididemis - coagulase negative
mannitol salt agar
proetin A (cell surface Fc receptor binds IgG) usually in staph aureus
virulence factors - antiphagocytic capsule, adhere to endothelial cells, techoic acid, catalase, hyaluronidase, staphylokinase, alphatoxin, beta toxin, panton valentin leukocidin, toxic shock syndrome toxin (can cause toxic shock syndrome)
streptococcus
gram positive cocci
catalase negative
causes hemolysis
strep pyrogenes (group A) - scarlet fever, rheumatic fever, pharyngitis
-capsule, cell wall (M protein), streptolysin S/O, hyaluronidase, DNase, streptococcus Ca/o peptidase, streptococcus pyrogenic exotoxins
spirochetes
treponema (syphilis)
borrelia (lyme disease)
enter through mucous membranes, have latent period, secondary and tertiary disease can occur
gas gangrene
clostridia perfringens
gram positive, spore forming, motile/nonmotile rods, strict anaerobes
double zone of hemolysis on blood agar and stormy fermentation
alpha toxin
rheumatoid arthritis
autoimmune
chronic inflammatory polyarthritis
monocyclic - 1 episode that ends
polycyclic - fluctuation of disease
progressive - increase in severity and symptoms unrelenting
rheumatoid factor, anticyclic citrullinated protein antibody
association with MHC class 11 HLA-DR4
TNF alpha is an important cytokine - causes upregulation of adhesion molecules
femoral neck fracture
leg ext rotated
posterior hip dislocation
limb shortening with flexion and internal rotation
anterior hip dislocation
usually with femoral head fracture
osteoarthritis
joint space narrowing, bone spurs
metastatic bone disease
prostate - blastic
breast - mixed lytic and blastic
pagets disease
thickened trabeculae/sclerotic bone, increased alkaline phosphatase, high output cardiac failure
bowed tibia
cotton wool appearance of skull
osteosarcoma
starburst appearance on xray
codmans triangle
osteoid osteoma
central nidus
osteochondroma
mushroom like stalk
calcium pyrophosphate deposition disease
pseudo gout
chondrocalcinosis - calcification articular cartilage
charcot joint
dense bone
degeneration
destruction of cartilage
deformity
debris
dislocation
sickle cell disease
hip avascular necrosis
H shaped vertebrae
local anesthetics
transient and reversible loss of sensation without loss of consciousness
block impulse conduction (limit influx Na)
vasodilators except cocaine
esters
benzocaine - only topical
chloroprocaine - short acting, not effective topically, epidural, less toxicity bc plasma metabolism
procaine
tetracaine - slow onset long acting, increase toxicity bc slow metabolism
cocaine
more likely hypersensitivity reaction
amides
bupivacaine. - cardiotoxicity
lidocaine
mepivacaine
prilocaine - intermediate aciton, cause methemoglobinemia
ropivacaine - cardiotoxicity
more systemic effects
sensitivity of nerve fiber
small diameter affected first
myelinated nerves affected first
low conduction velocity affected first
higher firing frequency affected first
higher pH easier to anesthetize
hyperkalemia enhances effects
hypercalcemia partially antagonizes effects
absorption
increased with sodium bicarbonate
administered with vasoconstrictor (epinephrine)
topical anesthesia
tetracaine, lidocaine, benzocaine, cocaine
direct application to mucous membrane
infiltration anesthesia
minor surgery
superficial to include skin and deeper structures only
field block anesthesia
anesthetic infiltrated into subcutaneous area surrounding operative field
contaminated wounds and skin abcesses
nerve block
drug injected near peripheral nerve trunk or plexus
most local anesthetics can be used
intravenous regional anesthesia
IV into limb and allowed to diffuse into surrounding tissue while tournequet keeps it in desired area
no adrenaline added
bupivacaine contraindicated
spinal block (intrathecal)
inject into subarachnoid space and mix with CSF
dense anasthesia of all peripheral nerves below injection
spinal anesthetic (epidural)
does not enter CSF
only bathes peripheral area of region injected
adverse effects
lidocaine/procaine may cause sleep and sedation
nystagmus, shivering, tonic clonic seizures, respiratory depression, coma, death
treated by maintaining airway, diazepam, succinylcholine
hypotension, cardiac arrhythmia (bupivacaine), methemoglobinemia (prilocaine, benzocaine, lidocaine, tetracaine), allergic reactions
drug interactions
sulfonamides, bactrim, azulfidine, alcohol. NSAIDs
Rheumatoid arthritis
Autoimmune disease affects joints and other organs (linked to HLA groups)
Chronic cd4 TH1/17
Rheumatoid nodes
Antibodies against Fc component IgG
Tx - antagonist of TNF and antibodies that deplete B cells
Jeuvenile arthritis
Fewer and larger joints than RA, more often has systemic disease
No rheumatoid nodes and few with rheumatoid factor
ANA positivity common
Ankylosing spondylosis
No RF
Inflammation of ligamentous attachments
HLA B27
Often SI joints, lead to joint fusion
Reactive arthritis
Triad of nongonoccocal urethritis, conjunctivitis, arthritis
reiters syndrome
reactive arthritis - post bacterial infection
symptoms - arthritis, inflammation of eyes and urinary tract, ulcers, sores, nodules
tx - only use NSAIDs or corticosteroids
post streptococcal reactive arthritis
less than 10 days after strep
tx - antibiotics for strep (penicillin or amoxicillin), NSAIDs, prednisone if NSAID fails
septic arthritis - acute monoarticular
get gram stain before treating
-gram negative = n gonorrhea so use ceftriaxone
*gram negative bacilli if no STD risk = pip/tazo and gentamicin or levofloxacin (immunocompromised) OR cefepime (immunocompetent)
-gram positive = staph aureus so use vancomycin
*gram positive but immunocompromised use vanc and ceftriaxone or cefdinir
once culture finalized tailor therapy
-MSSA = nafcillin, oxacillin, cefazolin
-MRSA - vancomycin
-N gonorrheae = ceftriaxone
septic arthritis - chronic monoarticular
do not treat empirically and wait for cultures to come back
septic arthritis - acute polyarticular
gram negative = ceftriaxone
no STD risk gram negative = ceftriaxone and vancomycin
septic arthritis - post intra articular injection
no empiric therapy and wait for culture to come back
osteomyelitis
empiric therapy = vancomycin and ceftriaxone
definitive therapy
-MSSA = nafcillin, oxacillin, cefazolin
-MRSA = vancomycin, daptomycin
-gram negatives = ceftriaxone, ciprofloxacin, levofloxacin
-enterococci = ampicillin or penicillin G
-streptococci = ampicillin or penicillin G
-with retained hardware add on rifampin
pyomyositis
immunocompetent - probably staph or strep use nafcillin, oxacillin, cefazolin
immunocompromised - broader coverage so use pip/tazo and vancomycin
-if anaerobes suspected use metronidazole/clindamycin
gas gangrene
clostridium perfringens - anaerobe so think clindamycin
empiric therapy - pip/tazo and clindamycin
*if risk of MRSA add vancomycin
definitive therapy - penicillin G and clindamycin
Medications for opioid use disorder
buprenorphine - partial agonist
methadone - long acting full agonist
naltrexone - competitive antagonist
buprenorphine
wait 6-12 hours after last heroin or short acting opioid use and longer after extended
at least 36 hours after last dose of methadone
if pt is on full agonist it will precipitate withdrawal
methadone
reduces cravings and prevents withdrawal
dispensed to outpatients at licensed opioid treatment programs
high risk of lethal overdose
naltrexone
no high or withdrawal
withdrawal should be complete (7 days for short acting and up to 14 for long acting)
also used for alcohol use disorder
adolescent idiopathic scoliosis
when measuring with scoliometer
-BMI <85% then xray when >7 degrees
-BMI>85% xray >5 degrees
cobb angle
-<20 degrees = observation
->20 degrees = bracing
->50 degrees = surgery
