Basic Science Flashcards
osteoblast derived from:
undifferentiated mesenchymal stem cells
mesenchymal cells become osteoblasts under what factors
- low strain and increased O2 tension
- Transcription factors RUNX2
- BMP
- Core binding factor Alpha 1 and beta-Catenin
Mesenchymal cells become cartilage under what conditions
Intermediate strain and low O2 tension
pulsatile PTH
stimulate osteoblast ativity
Osteoblasts secrete
Alk Phos RankL Type 1 Collagen Bone sialoprotein Osteocalcin (stim by Vit D)
Osteoblasts inhibited by
TNF Alpha
WNT’s causes
osteoblast proliferation and survival
=increased WNT=increased bone mass
Molecules that sequester wnt
Sclerostin and Dickkopf
these inhibit wnt and cause dec bone mass
Inhibiting these will allow WNT to work and cause increased bone mass
former osteoblasts surrounded by mature bone
osteocytes- from mesenchymal lineage
90% of cells in mature bone
control Ca and PO4 homeostasis
PTH function
stimulates clast activity
activates adenylyl cyclase
1,25 Vit D3 function on Blasts
increases matrix and alk phos synthesis, and production of bone specific proteins
Glucocorticoid effect on blasts
inhibits DNA synthesis, collagen, and protein production
prostglandins effect on blasts
stimulates bone resorption via activation of Adenylyl cyclase
Estrogen on blasts
anabolic and anticatabolic
inhibits adenylyl cyclase
calcitonin on CLASTS
inhibits clasts and dec bone resoprtion
lineage of osteoclasts
hematopoietic stem cells of macrophage lineage
mature osteoclasts bind surfaces by
integrin (AlphaVbeta3) or vitronectin receptor)
howship lacunae mechanisms
seal space below clast make tartrate resistant acid phosphatase carbonic anyhydrase=hydrogen ions lower pH increase solubility of hydroxyapatite crystals
Released by clasts after HA removed to degrade the organic matrix
cathepsin K-lysosomal enzyme
IL1 and IL 10 function
IL 1= potent stimulator of clast differentiation and bone resoprtion
- inhibited by anakinra which inhibits clasts and resorption
- found in TJA osteolysis scenarios
IL 10= suppresses osteoclasts
predominant collagen in bone
TYPE bONE collagen
provides the tensile strength
Most abundant non collagen protein in bone
osteocalcin
*inhib by PTH
Measure of bone turnonver in urine
60 % dry weight of bone is inorganics
Ca hydroxyapatite
Ca10(PO4)6(OH2)
attracts osteoclasts, direct regulation of bone density
osteocalcin
secreted by platelets, regulates calcium and organizes matric
osteonectin
similar to an integrin and is a cell binding protein
osteopontin
Arterial flow in mature bone is in which direction
centrifugal- inside to out, which is the net effect of the high pressure nutrient artery haversian canal system and low pressure periosteal system
with fracture how does blood flow in the bone
with fx, the centrifugal system is disrupted, the low pressure periosteal system predominates and the flow is out to in centripetal
flow in immature bone
out to in, due to high vasc periosteum, ceintripetal
Venous flow in mature bone direction
out to in centripetal
Bone replaces a cartilage model
enchondral bone formation
LongBones
Fracture Callus
bone made with DBM
aggregate of undifferentiated mesenchymal cells differentiate into osteoblasts which form bone
intramembranous-
flat bones
Distraction osteogenesis
Blastema bone
osteoblasts lay down new bone on existing bone
appositional bone formation
bone formation phase of bone remodeling
Periosteal bone enlargement
Disorder of enchondral bone formation
achondroplasia
disorder of intramembranous bone formation
cleidocranial dysostosis
Disorder of appositional growth
paget’s
melorheostosis
infantile hyperostosis Caffey Dz
when do bones begin to form in utero
6 weeks
primary ossification centers formed when at gestation
8 weeks
differentiation stimulated in part by binding of what to what
WNT binds to LRP5 and LRP6-
zones of enchondral bone formation
reserve zone
proliferative zone
hypertophic zone
metaphysis
Lysosomal storage dz causes dysfunction in what zone
reserve zone (gaucher’s dz)
decreased O2 tension occurs in what zone
reserve zone
stores lipids glycogen and proteoglycans
reserve zone
achondroplasia affects which zone
proliferative zone
growth hormone acts on what zone
proliferative zone
in this zone, growth is longitudinal, with stacked chrondocytes, cell proliferation and matrix production, O2 tension increases and proteoglycans inhibit calcification
proliferative zone
SCFE affect what zone
hypertrophic zone
3 sub zones of hypertrophic zone
maturation
degeneration
provisional calcification
matrix mineralization occurs in
hypertrophic zone
PTHrP effect on chrondrocytes
inhibits chrondocyte maturation
IHH produced by chrondocytes and does what
regulated (dec) expression of PTHrP
Thus increases chondocytme maturation
and increases matrix mineralization/bone formation
which zone widens in Rickets with little to now provisional calcification
Hypertrophic Zone
diastrophic dwarfism zone
reserve- TYPE II collagen synthesis defect
psueoachondroplasia zone
reserve, defect in processing PG
Kneist syndrom zone
reserve, PG defect
Giganstism zone
proliferative zone- increased GH
achon zone
proliferative - FGFr23
malnutrition, irradtiation and steroid excess zone
proliferative- dec prolif or matrix synthesis
Mucopolysacharidoses affect what zone
maturationa and degeneration zones of hypertrophic zones- deficicnecy in lysosomal acid hydrolases and storage of mucopoly’s- cells cannot prepare matrix for calcification properly
rickets and osteomalacia zone
zone of provisional calcification zone
acute hematogenous osteomyelitis
primary spongiosa of metaphysis-sluggis circulation and, reticuloendothelial deficiency, low PO2
osteopetrosis zone
Secondary spongiosa- abnormal clasts (cannot remodel internally)
function of secondary spongiosa
remodeling zone
scurvy zone
2ndary spongiosa-inadequate collagen formation
Osteogenesis imperfecta zone
2ndary Spongiosa abnormal blasts and collagen synthesis
metaphyseal displasia (Pyle dz) zone
secondary spiongiosa
SCFE zone in renal osteodystrophy
metaphyseal spongiosa
inheritence pattern for X linked Hypophosphatemic Rickets
X linked Dominant- one X allele hey have the trait,
branches of axillary artery
Screw the lawyer, save a patient! S: superior thoracic artery T: thoracoacromial artery L: lateral thoracic artery S: subscapular artery A: anterior humeral circumflex artery P: posterior humeral circumflex artery
study needed and tumor associated with Bekwith Wideman
need afp levels 3-4 times ayear until 8 yo abdominal and pelvic usg r/o wilms tumor hemihypertrophy and large tongue 10% risk of wilms tumor
extensor compartments of wrist
1- EPL and APB 2. ECRL/ECRB *Listers* 3. EPL 4, EDC, EIP 5, EDM 6 EDCU
What is an isotropic material
it has similar mechanical properties regardless of the orientation of the material. Examples of isotropic materials include metals, plastics, and methacrylate. Most biologic tissues are anisotropic, meaning their mechanical properties alter depending on the materials’ orientation to the applied stress.
spots for anatomic biopsy
o Wrist
dorsal 2nd compartment
site for biopsy distal humerus
o Distal Humerus = lateral triceps, brachialis muscle
biopsy spot proximal humerus
o Proximal Humerus = anterior deltoid muscle
illiac biopsy spot
o Iliac = thru superior abductor muscles
supraceteabular region biopsy spot
o Supracetabular = Smith-Peterson approach through TFL and rectus femoris muscle
femoral neck and head biopsy spot
o Femoral Neck and Head = transtrochantlric osseous approach
distal femur biopsy spot
o Distal Femur = posteromedial or posterolateral border of vastus medialis/lateralis muscle
tibia biopsy spot
o Tibia = subcutaneous border of tibia
patellar problem when converting HTO to total knee arthroplasty
patella baja
o Tibia = subcutaneous border of tibia
bone placed in longitudinal tension will tend to stimulate longitudinal growth, and that compressive longitudinal forces inhibit longitudinal growth
(think Dr. Dan’s thethering proecuderes0
Wolff’s law
bone remodels in response to mechanical stress, with the correlate that increased stress causes increased growth, and decreased stress leads to bone loss.
bone remodels in response to mechanical stress, with the correlate that increased stress causes increased growth, and decreased stress leads to bone loss.
affects bacterial protein synthesis through a unique inhibition of the bacterial ribosome. Linezolid binds to a site on the 23S ribosomal RNA of the 50S subunit, preventing formation of the 70S initiation complex and interrupting the translational process
penicillin abx inhibit what
bacterial cell wall synthesis
florquinonlones MOA
-cipro- DNA gyrase
rifampin MOA
DNA-dependent RNA polymerase is inhibited
Bacterial cell membrane depolarization interrupting DNA, RNA, and protein synthesis is the mechanism of action of
Daptomycin
glucagon is catabolic or anabolic in skeletal muscle
catabolic-hormone of starvation-mobilized stored energy
insulin is catabolic or anabolic in skeletal muscle
anabolic-hormone of plenty
lactate level for DCO
should be less than 2.5, if greater then consider DCO
fibrinogen level for DCO
should be greater than one, if less consider DCO
base deficit for DCO
should be between -2 to =2=if not consider DCO
platelet level for DCO
should be 70,000 or greater, if not consider DCO
myxoid liposarcoma translocation
t(12;16)
synovial sarcoma translocation
t(X;18)
alveolar rhabdomyosarcoma translocation
t(2;13)
ewing sarcoma translocation
t(11;22)
clear cell sarcoma translocation
t(12;22)
innervation of teres minor
axillary nerve
innervation of supraspinatus
suprscapular nerve
innervation of infraspinatus
suprascapular nerve
innervation of teres major
lower subscapular nerve and thoracodorsal
innervation of suscapularis
upper and lower subscapular nerve
mutation in FGFR-3
Achondroplasia
mutation in glucoceribrosidase
Gaucher’s dz
GNAS mutation
Fibrous displasia (shepherds crook proximal femur)
SLC26A2 gene which affects a sulfate transporter.
Diastrophic Displasia
mucopolysaccharidosis
due to accumulation of keratan sulfate and presents around 2 years of age with waddling gait, genu valgum, thoracic kyphosis, cloudy corneas, and normal intelligence. C1–C2 instability (due to odontoid hypoplasia) can be seen
Morquio’s syndrome
slowly adapting skin receptors that detect pressure, texture, and low frequency vibration and can be appropriately evaluated by static two-point discrimination.
Merkel’s
rapidly adapting sensory receptor, is very sensitive to touch
meissner’s corpuscle
ovoid in shape, measuring approximately 1 mm in length. They respond to high-frequency vibration and rapid indentations of the skin
pascinian corpuscle
slowly adapting receptors that detect stretching of the skin.
ruffinian
This method is used to compare the difference between two observed means.
Student’s T test
Spinal muscular atrophy (SMA) is caused by a deficiency in
survival motor neuron protein
synovial sarcoma translocation
x,18
myxoid liposarcoma translocation
12,16
ewings translocation
11,22
clear cell sarcoma translocation
12,22
myxoid chondrosarcoma
9,22- BCR/ABL?
antibiotic that can precipitate serotonin syndrome
Linezolid, and benzo’s reverse it
CA- MRSA with and w/o + D test what do you prescribe
IF D test is += this implies inducible resistance to clinda-and you must give oral doxy
if d test is negative- it is susceptible to clinda and you give clinda
If systemic signs of illness-give IV vanc
If superficial and mild infection-give Orals
level of study
“include randomized controlled studies with follow-up>80% and systematic review of Level-I RTC studies (homogenous studies)
Level I
this study level includes
evidence include case control studies, retrospective cohort studies and systematic review
level III
vidence include case control studies, retrospective cohort studies and systematic review
level II
evidence include case series with no control group (or compare to a historical control group)
level IV
level of evidence including expert opinion
level V
Rett Syndrome gene and ionhertience pattern
Affects Grey matter of brain
X linked Dominant
C shaped Curve
Seizures
MECP2 gene mutation
type of collagen increased in OA
Type X collagen is seen in articular cartilage in the region of the interface with subchondral bone in most OA patients.
What is the role of the homeobox gene in the axial skeleton
regulate somitogenesis
Low serum phosphate and normal calcium levels are found in
X linked hypophosphatemic rickets
linked to the PHEX gene
ow serum phosphate, normal serum calcium and 25 hydroxycholecalciferol levels, and inappropriately low 1,25-dihydroxyvitamin D3.
*cannot activate the inactive form or Vit D
defect in mineralization of osteoid matrix caused by inadequate calcium and phosphate that occurs prior to closure of the physes
Rickets
*osteomalacia after physis closes
deficient bone Quantity and Not quality of bone mineralizetion in adults
Osteoporosis
- disruption in mirco-arcitecture
- they have less total amount of normal appearing bone
NON nitrogen containing bisphosphonates
etidronate
clodronate
tiludronate
*mechanism of action
produce toxic atp analog
NITROGEN CONTAINING bisphosphonates pamidronate alendronate- fosomax risderonate actonel zoledronate reclast ibandronate boniva
inhibit farnesyl pyrophosphate synthase
xray findings in peds rickets
increased physeal width and cortical thinning/bowing
rachitic rosary on ribs
Vitamin D resistant (familial hyphophosphatemic rickets)
3 types?
X linked- most common
Autosomal Dominant-
Autosomal recessive
Cause of X linked vitamin D resistant Familial Hypho-phosphatemic rickets
PHEX gen
leads to increased levels of FGF23, which decreases renal phosphate absorption and suppresses renal 25-(OH)-1α-hydroxylase activity
Characteristic of Familial Hypophosphatemic rickets
caused by inability of renal tubules to absorb phosphate
GFR is normal
vitamin D3 response is impaired
AD familial hyphophosphatemic rickets
results from mutation in FGF23
leads to decreased FGF23 degradation
AR familial hypophosphatemic rickets
results from mutation in dentin matrix protein 1 (DMP1) gene
leads to impaired osteocyte maturation and bone mineralization, and increased levels of FGF23
VIT D deficient (nutritional rickets) pathophysiology
low Vitamin D levels form diet lead to decreased intestinal absorption of calcium
low calcium levels leads to a compensatory increase in PTH and bone resorption
bone resorption leads to increased alkaline phosphatase levels
Only rickets with normal calcium
X linked hypophosphatemic rickets
renal osteodystrophy lab findings
Low calcium
High PTH
HIGH PHOSPHATE!! kidney suck and cant get rid of it
Hyperparathyroidism lab findingds
90% due to adenoma
very low phosphate
Hypophosphatasia inheritance
auto recessive
Hypophosphatasia labs
high calcium
hi phosphate
very low Alk phosphate
caused by a mutation in the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP)
hypophosphatasia
phosphoethanolamine in the urine diagnostic for
hypophosphatasia
COMP is associated with
Multiple Epiphyseal Displasia type I
Double patella
fibrillin is associated with
Marfan’s syndrome
COL2A1 is associated with
SED tarda and SED congenita
RUNX2/CBFA is associated with
cleidocranial displasia
