BS 3 Flashcards
What is a centromere
What disease is Abs vs centromere
Centromere = central part of the chromosome that holds duplicated sister chromatids together
CREST = anticentromere Abs
Calcinosis
Raynauds
Esophageal dysmotility
Sclerodactyly
Telangiectasia
Disease for anti-dsDNA Abs
SLE
Disease for anti-histone Abs
What is a histone
Histone = protein core for spooling DNA
Drug induced SLE
What is a topoisomerase
Disease for anti-topoisomerase Ab
What abx inhibits
Topoisomerase = DNA gyrase aka unwind DNA for use
Anti-TP Ab = diffuse scleroderma
Quinolone abx inhibit DNA gyrase
What is the process to make
DNA -> mRNA
mRNA -> protein (and where does this occur)
DNA > mRNA = transcription
mRNA > protein = translation (in ribosomes)
What proteins are involved in the following steps of transcription:
1 Binds DNA to select genes for transcription
2 Reads DNA to make mRNA
- What abx works at step 2
- Transcription factors - bind DNA to tell what parts to code
2 RNA polymerase - reads DNA > mRNA
Abx: rifampin = binds RNA pol = Xs bact RNA synthesis
Disease for anti-Smith (anti-Sm) Ab
What is a Smith
Anti-Sm = SLE
Smith = snurps
Ribonucleoprotein that cuts out introns, joins exons
- Exon = DNA/RNA that codes for proteins
- Intron = DNA/RNA that does not code for protein
What is the difference between human vs bacterial ribosomes
Human = 80S = 60 + 40 subunits
Bacteria = 70S = 50 + 30 subunits
Where do these abx work:
Clindamycin
Macrolides
Linezolid
AminoG
Tetracycline
50S subunit bact ribosome:
Clindamycin
Macrolides
Linezolid
30S subunit bact ribosome:
AminoG
Tetracycline
Name the disease/mutation/mechanism:
Ragged cafe au lait spots
Precocious puberty
Hypothyroidism
Cushing
Ground glass lesions on XRs
Fibrous dysplasia
Mutation = activation GNAS1
Mechanism = more cAMP
Disorganized fibrotic bone matrix
What is the disease when fibrous dysplasia is polyostotic
McCune Albright syndrome
Why is fibrous dysplasia NOT an inherited disorder
Bc is a post zygotic somatic mutation - aka error in the mitosis of the zygote
Mutated genes won’t survive reproduction
Name the disease/inheritance/mutation/mechanism:
Skin bumps
Smooth cafe au lait
Iris pigmentation
Tibial pseudarthrosis
Scoli
NF1
AD
Mutate tumor suppressor gene
Xs Ras protein = stim cell growth
Hamartomas = Lisch nodules iris, tibial pseudo (AL always looking for a reason for tibial bowing)
Name 10 common AD diseases (structural proteins!)
1 Achon = FGFR3
3 Pseudoachon = COMP
3 Marfans = fibrillin
4 ED = COL1
5 OI = COL1
6 SED = CO2
7 Kneist = COL2
8 Stickler = COL2
9 MED = COL9, COMP
10 Schmid = COL10
Name 7 common diseases that are AR (enzyme gene deficits)
1 Diastrophic dysplasia = sulfate transport
2 Hurler = alpha-L-iduronidase
3 Sanfilippo = heparan sulfamidase
4 Morquio = galactose sulfatase
5 Gaucher = cerebrosidase
6 Osteopetrosis = CA
7 Homocystinuria = cystathionine synthase
Name 5 common XL recessive disease
XL-R disease: who is the carrier, who is affected
Mother = carrier (X*X)
Sons have 50% chance being affected
1 Hunter mucopolysacc = iduronate sulfatase
2 SED tarda = TRAPP
3 Hemophilia (A = F8, B = F9)
4 Duchenne MD
5 Becker MD = DMD gene, Xp21 dystrophin
XL dominant diseases
- If dad is the carrier, which kids affected
- If mom is the carrier, which kids affected
Dad = XY
All daughters affected XX
No sons (X from mom)
Mom carrier = X*X
50% daughters and sons affected
What is the general ortho issue for Downs? How does this make sense genetically
COL6 is is on chromosome 21 - overexpressed
Ortho issue = LAXITY
- Hip instab
- Patellar dislocation
- AA instab
Multiple myeloma
- Genetic cause
- Cell changes
- Lab findings
- Bone findings + mechanisms (2)
Chr 13 deletion = worse prognosis
Proliferate monocolonal B cells = plama cells
Lab = SPEP (M spike), UPEP (Bence Jones proteins)
Bone: lytic lesions
1 Cells release PTHrP = more RANK osteoclast
2 DKK1 inhibits blasts
Name the disease/mutation/mechanism
Short, fat kid
Hypotonic at birth
MR
Scoli
Prader Willi
Delete paternal ch15
Activates a silent maternal gene
Ewing
- Genetics
- Cells involved
- Presenting sx/population
t(11,22) translocation
- Pat Ewing’s jersey number = 33 (11+22=33)
EWS/FL1 fusion protein
Small blue cells, CD 99 marker (3x33)
KIDS
B sx: pain, fever
Long bone diaphysis
Name the gene translocation:
Synovial sarc
Clear cell sarc
Myxoid liposarc
Myxoid chondrosarc
Rhabdomyosarc
Synovial sarc - t(X, 18)
Clear cell sarc - t(12, 22)
Myxoid liposarc t(12, 16)
Myxoid chondrosarc t(9, 22)
Rhabdomyosarc t(2,13)
What cell is implicated w/ elevated alk phos
3 diseases with elevated alk phos
Alk phos = osteoblasts
Rickets
Osteomalacia
Paget
What is a disease state with LOW alk phos
Inheritance
Gene mutation
Hypophosphatasia
AR
Gene: TNSALP
How does BMP2 work?
Infuse
Inflammation -> bone formation
Also why see seroma formation
Fibrodysplasia ossificants progressiva:
What is it/presentation
Pathognomonic finding
Inheritance
Mutation
Stone man syndrome - see ossification of STRAP + IP muscles
Form HO from injury
Pathognomonic: 1st ray deformities at birth
AD
Gain of function BMP receptor = BMP4 over expressed
Which factor controls each:
Distal/prox
Ulnar/radial
Dorsal/ventral
Distal/prox - FGF (via apical ectodermal ridge)
Ulnar/radial - SHH (via ZPA)
Dorsal/ventral - Wnt / B catenin
Achondroplasia:
Inheritance
Mutation
Which ossification affected
Which part of the growth plate affected
AD
FGFR3 receptor
Endochondral ossification
Proliferative zone (where FGF works)
Function FGF23
Disease associated with overactive FGF23
Inheritance/mutation
Trt
Trash PO4
- Less renal reabsorption
Disease: hypophosphatemic rickets
- X dom PHEX mutation = cant breakdown FGF23 = low PO4
Trt = bursoumab = anti-FGF23
Disease associated with low FGF23 activity
Cause
Tumoral calcinosis
2/2 chronic renal failure - cant excrete PO4
Occasional genetic disorder that decreases FGF23
CaPO4 deposits throughout the body
3 diseases related to SHH issues
SHH = radio/ulnar
Polydactyly (post axial) = too much SSH
Mirror hand
Fib hemi = too little SHH
Fib hemi:
Associated knee finding
Absent ACL
Name the 3 types of tibial bowing and any associated conditions if applicable
AL = Aways Look for NF
AM = Absent/Missing bones = fib hemi
PM = Probably Mild, +/- calcaneovalgus
What is the classic example of Wnt disorder
Nail patella syndrome
Aplastic/hypoplastic patella
Iliac horns
Describe intramembranous ossification
Is Wnt high or low?
How does this affect SOX9/Runx2?
Mensenchymal stem cells direct to osteoblasts
No cartilage model
Wnt high (osteoblast differentiation)
Runx2 high / Sox9 low
Ie 1ary bone healing
Cleidocranial dysplasia:
Inheritance
Mutation
Clinical manifestations
AD
CBFA/Runx - poor intramemb ossification (flat bones)
No clavicles
Describe enchondral ossification
Is Wnt high or low?
How does this affect SOX9/Runx2?
Stem cells -> chondrocytes = cartilage model, later replaced by bone
Ie frx callus, growth plates
Wnt low (favors chondrocytes) - increases later when replacing the cartilage matrix w/ bone
Sox9 high / Runx2 low
What is the main goal of Wnt
Increase bone!
Osteocytes:
How do they communicate
What is the main signaling molecule
Communicate via gap jxn w/ connexin
Molecule = sclerostin
- Blocks Wnt/B catenin = inhibits osteoblasts
What 2 things inhibits sclerostin production?
What medicine Xs sclerostin
1 Mechanical loading
Sclerostin decreases bone mass
Why weight bearing (mechanical loading) = good for bone mass
2 Pulsed PTH
Med = romosozumab
Approved for osteoporosis
Sclerosteosis:
Inheritance
Mutation
Clinical presentation
AR
SOST defect
Thick cortices (too much bone)
- CN pinching: deaf, blind
- No frx bc bones so hard
What does dickkopf protein (DKK1) do
Decrease bone
Blocks Wnt/B catenin
Describe the RANK-L/RANK pathway
RANK-L from osteoblasts/cytes
Binds RANK
Stimulates clast formation
RNK is a receptor on clasts
Function of osteoprotegrin
Blocks RANK-L/RANK
From osteoblasts
How blasts inhibit clasts
What cell does Wnt signaling work on
Mesenchymal stem cells to drive differentiation to osteoblasts
What molecule turns osteoclasts on vs off
On: RANK-L
Denosumab is an Ab to RANK-L
Off: calcitnoin
2 types of bisphosphonates + mechanism
Nitrogen = block synthase enzyme
- Alendronate, risedronate, pamidronate, zoledronate
Non-nitrogen = compete with ATP
- Tiludronate, etidronate, clodronate
How do osteoclasts break down bone? 4 major cell enzymes
Carbonic anhydrase
Cathepsin K
TRAP
ATPase / Cl- channel
