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Flashcards in Bones/Joints Deck (41):
1

Normal skeleton

essential for mineral homeostasis. 65% inorganic, 35% organic.

-inorganic matrix- Calcium hydroxyapatite- mineral homeostasis is 99% of calcium stores, 85% of phosphate stores 65% of sodium and magnesium stores. provides bone strength
-Organic- bone cells- osteoprogenitor cells, osteoblasts, osteocytes. hematopoietic progenitor cells, osteoclastic precursors and osteoclasts.
---Bone Matrix- type 1 collagen-29%(90% by weight of organic component)- non collagenous proteins (3%) , 10% minerals, 10% water
---osteoclassts- derived from heamtopoietic progenitor, intimately related to bone surface, releases proteolytic enzymes, role in bone resorption, have a howship lacunae.
---bone matrix-

Types of bones- osteoid-unmineralized matrix, woven bone, lamellar bone- cortcal an cancellous

Peak bone mass is early adulthood with 5-10% turnover/ year

Childhood and adolescence you have skeltal growth and osteoblastic function predominates, bone loss is more than bone deposition.

After fourth decade, you get more bone deposition than bone loss. resorption exceed renewal - progresseive bone loss.

2

Osteoblasts

synthesize proteins, initiate mineralizatio, make bone, regulate osteoclasts. osteoid matrix 12-15 days to bone- mineralized matrix
-key cell in regulation of bone remodeling,
bind hormones,
-repsonds to stimulation from osteocytes
-responds to stimulation from blood borne factors
- stimultates development of osteoclasts
-activates osteoclasts using RANKL

3

RANKL

Receptor activator of NF- Kappa B ligand
- expressed in OSTEOBLASTS
-upregulated by PTH, Vitamin D3, some malignancies
-binds to RANK(TNF famly) on OSTEOCLASTS and is the precurosr to activate them
- function inhibited by osteoprotegrin(TNF FAMILY)- binds to RANKL acting as a decoy to prevent RANK-RANKL interaction.

PTH, IL-11, D3, act on osteoblasts which use paracrine molecular mechanisms to activate osteoclasts, this causes prolifeation, fusion, differentiation, and survival

M-CSF causes increase in osteocalsts OPG (Decoy which blocks RANKL and checks stimulation of osteoclasts)

4

Osteoporosis

Epidemiology: severe disease of elderly

Morphology:Localized or diffuse, primary or secondary, diminished bone mass.

Etiology: physical activity decreasing, genetic factors, nutrition, causes loss of bone mass,
-In women: menopause causes decreased serum estrogen, increased IUL-1,6,TNF increased expression of RANK, RANKL, increased osteoclast activity
- in aging- decreased replicative activity of osteoprogenitor cells, decreased synthetic activity of osteoblasts, decreased biologic activity of matrix bound growth factors, reduced physical activity
Secondary- Hyperparathyroidsim, hyperthyroidism, diabetes, addison's disease, pituiatary tumors
-neoplasms- carcinomatosis, multiple myeloma, paraneoplastic disease
-gastrointestinal- malnutrtion, hepatic insufficeiency, vitamind D or C deficiency, malapsortion.
-drugs, chemo, corticosteroids, alcohol, immobilization.


Complication: fracture

5

Hyperparathyroidism

Pathogenesis: increased PTH causes stimulation of osteoblasts which increases RANKL to ativate ostoclasts- this causes increased osteoclastic activity and massive bony reorption. unabated osteoclastic activity causes osteoclastic tunneling, giant cell tumor like mass, neovascularization, hemorrhage, and brown tumor.

6

Renal osteodystrophy

chronic renal failure leads to hyperphosphatemia which leads to hypocalcemia and secondary increase in parathyroid hormone.

Hypocalcemia caused by decerased vitamin D metabolism in kidney (Inhibition of foncersion of vitamin D to active metabolites by phosphate, or diminished intestinal absorption of vitamin D.

-iron and aluminum accumulation in bone from dialysate, which prevents further bone deposition.

will see increased parathyroid hormone, increased osteoclastic activity, increased bone reorption, decreased mineralization (osteomalacia), osteoprosis, growth retardation.

7

Vitamin D deficiency

etiology- malnutrition, malabosrption, receptor abnormalities, lack of sun exposure

Pathogenesis- abnormal or under mineralized matrix, persistent hyaline cartilage, fractures, skeletal deformity

rickets in childrne, osteomalacia in adults

8

Scurvy

Vitamin C deficiency
-failed cross linking of collagen, fragile capillaries and venules leads to subperiosteal hemorrhages,
-defective osteoid synthesis leads to microfractures and bony deformities.

9

Paget's disease

Epidemiology: more commin in whites, in england, france, austria, US, Germany, New Zealand, Australia, Less in Japan, China, Scandinavia, Africa
-5-11% of whites, adults, M=F

Etiology- virally induced (paramyxovirus (measles, RSV)- nucleocaspid antigens identified in osteoclasts, these are slow viru diseases
-genetic predisposition- mutation in p62

Pathogenesis: virus stimulates IL-6 , IL-6 and M-CSF activate osteoclasts, osteoclasts are hyperresponsive to RANKL and vid D. p62- increased RANK/RANKL signalling which increases osteoclasts.

course
---Stages- osteolytidc stage- osteoclastic activity, patchy, florid. Mixed lytic and blastic stage- predominantly osteoblastic, Osteosclerotic (burnt-out) stage: end stage increase in bone mass.

Diagnosis- Increase in serum alkaline phosphatase, increase in urinary hydroxyproline
-x-ray
-may be monostotic or polyostotic

Complications- Deformities- pain due to compressed nerves
-fracture/microfractures leads to pain
-degenerative joint disease leads to pain
RARELY: high output cardiac failure (osteoblastic phase) or Tumors- sarcoma 5-10% they are high grade and lethal, Giant cell tumor, Extra osseous hematopoiesis.

10

Achondroplasia

Etiology: abnormal chondorcyte development dwarfism
-AD FGFR3 mutations

Pathogenesis: disordered proliferation of chondrocytes in cartilage and anlage and growth plate leads to decreased proliferation, decreased hypertrophy and incompelte endochondroal ossification

Clincal: shortened limbs and ribs. Normal head, IQ and reproductive system also life expectancy.

11

Osteogenesis Imperfecta

Epidemiology: most commonly recognized congenital disease affecting collagen produciton

Etiology:Group of phenotypically related disorders caused by deficiencies in type 1 collagen synthesis-

Pathogenesis- involves bone matrix and other connective tissues with type 1 collagen, joints, eyes(blue sclera), skin, ears, teeth

multiple subtypes.

12

Ehler Danlos Syndrome

Indian Rubber man
Etiology: hetrogenous group of connective tissue disorders recently classified in different types

Morphology: bone is osteopenic,, kyphoscoliosis, spondolisthesis.

clinical: hyperextensibility of skin, easy bruising, hypermobile joints, aortic dissection, blue sclerae

13

Marfans Syndrome

Etiology: hetergenous group of AD connective tissue disorder affecting bones, heart, aorta, and eyes
-mutation in locus of fibrillin gene on chromosome 15

Clinical: tall with long extremities and long tapering fingers and toes, hyerflexible joints, kyphosis, scoliosis, pectus excavatum,
-eyes- subluxation of lens, ectopia lentis
-CVS: Mitral valve prolase, Aortic dilatation due to cystic medial necrosis- AR; aortic dissection.

14

Osteopetrosis

Brittle bone disease

Etiology: dysfunction of carbonic anhydrase

Pathogenesis: inability of osteoclasts to degrade pre-existing cartilage and bone, persistence of cartilage anlage ( Primary songiosum) in medullary cavity
-progressive deposition of bone on pre-existing matrix without osteoclastic acitivity ( or without osteclasts.

15

Osteomyelitis

inflammation of bone or marrow

Etiology: hematogenous seeding from systemic disease or direct inoculation Bacteria is the most common fungal, viral, protozoal is rare
no organisms in 50%
- staph aureus in 80-90% because it has receptors for bone matrix components like collagen
-Gram rods( E. Coli, Klebsiella, Psudomonas) - GU infection, IV drug abuse
- Mixed bacterial infection in direct inoculation
-H influenzae in neonates
- Groub B streptococus in neonates
-Salmonella in Sickle cell disease.

16

Acute Osteomyelitis

young growing children, adults less than 50 years old, male 2:1. Locations in long tubular bones like femur, tibia, or humerus, also vertebral bodies.
- predisposing factors: catheter, trauma, infection, underlying disease, IV drug abuse.
- emergency in young children and infants

Course- subperiosteal abscess which ruptures into soft tissue which then abscesses draining into sinuses. Extension into joint space in infants and young children leads to extensive articular damage and permanent disability.

Clincal/complications: acute inflamamtion bone necrosis, subperiosteal abscess, progressive ischemia leads to segmental bone necrosis (sequestrum) Surrounded by viable new bone (involcrum) formation
-draining sinus tracts, extension into joint space

Treatement- treat Early with IV antibiotics, 4-6 weeks
exception, children with hematogenous spread can use oral therapy if organsims is suceptible and if you have good compliance with a rapdi response
-consider surgical debridement.

17

Evolution of Chronic Osteomy

Etiology: 5-15% of acute osteomyelitis do not resolve and become chronic this is due to delay in daignosis, inappropriate antibiotics or not long enough
-inadequte surgical debridement because of extensive necrosis
-underlying medical condition.

Pathogenesis: chornic inflammation, resorption of dead bone, deposition of woven bone. BRODIE ABSCESS: intracortical abscess
-Sclerosing OM of Garre: Jaw- extensive new bone obscurring the underlying bone

Complications: Recurrent acute exacerbations, pathologic fracture, secondary amyloidosis, endocarditis, sepsis, septic arthritis, Rarely malignant conditions like SquCC of fistula tract, Sarcoma of infected bone.

18

Tuberculous Osteomy

1-3 % of patients with pulmonary TB immunocompetent or compromised, location in spine (pott's spine) then the knees then the hips. Is a burrowing abscesses with caseating granulomas and calcification.
-very destructive, spreads through medullary cavity, causing extensive necrosis. extends thru IV discs involving multiple bones, difficult to control.

19

Arthritis

etiologies- infection, immune mediated, crystal deposition. degeneration.

20

osteoarthritis-degenerative joint disease

most common arthritis

Etiology- due t osteophyte formation not synovial inflammation.

Primary- aging phenomenon- aligoarticular, 80-95% of people over 65 years.
Secondary- younger patients- predisposition of diabetes, hemachromatosis, ochronosis, obesity, congenital deformity, is severe and poly articular. INJURY can as well.

pathogenesis- progressive destruction of articular cartilage, not true inflammatory arthritis but has a component of inflammation,
-changes in components of articular cartilage- altered proteoglycans and diminished pliability of collagen
-changes in chondrocytes- IL-1 and TNF alpha break down the matrix, inhibit type II collagen synthesis
-other changes- Proinflammatory cytokines, inflammatory cells.
-direct injury leads to decreased cartilage synthesis and increased ezyme break down, metalloproteinases breakdown PG(Stromelysins) and collagen (collagenases), they also are regulated by IL-1 and TNF. Genetic predisposition (cartialge abnormalities and collage genes mutations,
-injury and repair of the subchondral bone and synovium (secondary to cartilage degeneration.
-repair causes fibrocartilage to grow over the articular cartilage from periphery which leads to formation of osteophytes.
- JOINT MICE- microfractures causes chunks of dislodged bone and cartilage which leads to loose bodies(joint mice)

found at the center weight bearing portion of the joint

can form subchondral cyst- this is synovial fludi forced into subchondral microfractures in a ball valve manner the fluid collecition is walled off.

synovial changes may be present but are secondary to cartilage degeneration, synovial proliferation, hyperplasi, inflammation (pannus if severe0 this leads to fibrosis and ankylosis.

In spine you see narrowing of iv space, osteophyes, nerve impingement and pain.

21

Primary osteoarthritis

most common form of arthritis, primary typically involves a variable number of joints in characteristic locations- neck, back,femur and hips, DIP(haberden's nodes), PIP(Bouchard's nodes), 1st carpometacarpal joint (most commonly affected joint in the hand can cause subluxation and "Squaring", knee, big toe.
-age 75% of persons over age 70 have osteoarthritis.
-female sex is more susceptible along with the obese, and it is hereditary.

is systemic
can present unilateral but will usually end up bilateral.

-Fibrillation and vertical cracking- injury leads to chondrocyte proliferation-cloning, altered water (increased)/ proteoglycan (decreased content) can lead to chondromalacia softening
---- type II collagen has decreasd synthesis and increased breakdown.

22

secondary OA

due to trauma and neuromuscular dysfunction, metabolic disorders.

23

Rheumatoid arthritis

Epidemiology- prevalence of about .5-1%
female :2.5:1 ratio

Etiology- Genetic predisposition(HLA-DRB1 locus), risk factor- smoking, infections of EBV and E. Coli or stress

morphology- symmetrical arthritis, typically of the hands and feet, also involving the ankles, knees, wrists, elbows and shoulder
-joint destruction occurs early and is a marker for disease progression.
-systemic disease manifested by polyarthritis: PIP, MCP, wrist involvement, knees, not hips
-papillary synovial hyperplasia, bulbous fronds, lympohcytes + plasma cell infiltrate, perivascular lymphoid aggregates, vascular congestion.
-considered a symmetrical arthritis and distal joints.
- you also get fibrin over synovium and joint space and formation of rice bodies.
Synovial pannus, that develops on the periphery, and has a pannus that grows acros sthe joint, this can eventually lead to fibrosing ankylosis.
periphery

Pathogenesis- icreased osteoclastic activity due to RANKL produced by the activated T cells and synovial fibroblasts, this can lead to subchondral cysts, osteporosis(localized and systemic.
you don't get osteophytes you get loss of cartillage at t


Complication- soft tissue, ehumatoid noudels, lung involvemen(end stage jung disease, vasculitis,(MI, Cerbrovascular disease, renal failure, mesenteric and intestinal infarction, gangrene), uveitis(Juvenile RA), systemic amyloidosis, iatrogenic effects of Tx immunosuppression, life expectance is decreased by 3-7 years.


clinical- pain inflammation, swelling, destruction.

24

OA vs RA

OA- AM stiffness is less than 30 minutes, Symptoms are worse with activity, on weight bearing joints and PIP and DIP, is non inflammatory, has reparative activty and new bone formation- osteophytes

RA- AM stiffness is more than an hour, symptoms better with activity, joint distribution in the wrist, MCP, PIP, systemic disease, fever, weight loss, inflammatory, no reparative bone formation- periarticular osteopenia

25

Seronegative spondyloarthropathies

hetergenous group of diseases
arthritis one of several manifestations
in part immune mediated, similar but milder disease than RA, has HLA -B267

chronic synovitis, sdestruciton of articular cartilage and subchondrla bone, fibrosis and narrowing of joint space, (fiborisng ankylosis, ossification of fibrous tissue (bony ankylosis, joint immobility, sacroiliac joints and spine (SA) most common is ankylosing spondylitis.

26

Gout

Acut gouty arthritis- red painful swollen

chroinc tophaceous gout- fibrosis, crystal deposits, joint destruction- deposits in areas of low temperature, incite inflammatory response, Bone and joint destruction, may ulcerate skin.

Gouty tophus- large crystalline masses with asocaited tissue reaction.

etiology- hyperuricemia( Primary is genetic) secondary is due to increased neucleic acid turnover, leukemia, alcohol, obesity, drugs, renal disease, purin rich diet, peak in 5th decade, linked to duration of hyperuricemia (20-30 years)

27

Infectious arthritis

extension of osteomyelitis, heamtogenous seeding, organisms, bacteria: rapid joint destruciton

S. aureus- children
N. Gonnococcus- adults
mycobacteria,
Borrelia (lyme disease

Viral- parvovirus B 19

28

General bone tumor

incidence- most common malignant tumor is a METASTASIS, 3000 new primary bone tumors/ year in US. sarcomas result in 1400 deaths per year. -

29

Bone tumors

Diaphysis- Ewing's Sarcoma, Adamantinoma

Metaphysis- Osteosarcoma, chondrosarcaoma, osteochondroma, aneuryslma bone scyst

Epiphysis- chondroblastoma, Giant cell tumor.

Clinical- beinign usually asymptomatic-
Malignatn are agressive- Pain, pathologic fracture, metastases,

Morphology/Radiology- site and appearance are clues to diagnosis.
Benign- well circumscribed, scalloped border, no destructive growth, no invasion of other tissue or joint, usually small, typical in younger patients.
Malignant- usually high grade, poor prognosis, important predictor of behavior, determines likelihood of adjuvant therapy, tumor stage, predicts clinical outcome, metastaic disease is the highest stage.

30

Osteoid osteoma

Tumor of young adults with male prediliction and predilection for appendicular skeleton, classical clinical presentation, nocturnal pain, alleviated by aspirin.

presents with irregular trebeculae
nydus, tumor of osteoblates, produced irregular dens or thickening of the bone, they have a dense thickend bone around a central nydus which acn look like a lytic lesion on x-ray, they look like nrmal osteo blasts its the way the ne is forming its its irregular trebeculae.

31

Osteoma

benign, mature bone, predilection for craniofacial bones, Gardner's syndrome can cause destructino of sinus and sinusistis. they are cortical bone growing where it shouldn' be, could be in medullary space as well. they are part of GARDEN'ERs disease or FAP

32

Osteosarcoma

Epidemiology- most common bone sarcoma- bimodal age distribution common Elderly (paget's radiation) children and young adult

location=- metaphyseal (long bones) in youth sit of growth plates, flat bones in elderly.

Etiology- Hereditary tumors- p53 mutations (Lifraumeni), retinoblastoma gene (hereditary Rb)
-sporadic p53 mutations, MDM2(inactivates apoptotic capacity of p53) rb mutations are rare.

Pathology: Anatomic location- intramedullary(low grade, intracortical ( high grade) juxtacortical ( low or high grade)

Grade1 mild cytologic atypia,
grade 2 intermediate cytologcial atypia
grade 3 high grade, pleomorphic cytological atypia

high grade with chemo, low grade with surgery.
can be osteoblastic, chondroblastic, fibroglastic.

33

Cartilage tumors

most are benign , types of cartilage, hyaline found in tumors and normal, myxoid found only in tumors, fibrocartilage, rare in tumors, elastic, extremely rare in tumors.

34

osteochondroma

benign cartilage tumor of metaphysis, young adults, occur only in bones with endochondral ossification.

Etiology is unclear, assumted to arise from displaced fragmetns of growth plate, new evidence suggests clonal proliferation EXT gene famlily mutations.

usually grow away from the joint.

35

enchondroma

Benign- Hayline and myxoid cartilage. Metaphyseal and diaphysseal, medullary cavity not on surface. , may erode but not invade the cortex, present with pathologic fractures. Solitary or syndromic (Ollier's or Mafucci's disease) may give rise to chondrosarcoma.

36

Multpile endochondromatosis

Ollier's Disease, disfiguring, 10% develop chondrosarcoma, usually fingers or long bones

Mafucci's disease- endochondroma and soft tissue vascular tumors. 20% develop chondrosarcoma, 100% develop another extraskeletal malignancy.

37

Chondrosarcoma

typically older adults

Pelvis, humerus, proximal femur

may arise in enchondroma (low grade)

many arel ow grade (1/3) do not metastasize but may recur and de differnetiate

High grade metastasize hard to manage when this happens.

38

Giant cell tumor of the bone

Benign locally aggressive tumor, 4-5% of all primary bone tumors age 20-40, epiphysis, end of long bones, x-ray: expanding lytic lesion and soap bubble appearance. they are sually skeltally mature.

39

Ewing's Sarcoma and Primitive neuroectodermal tumor PNET

Etiology:family of small blue cell tumors with a characteristic t(11:22_ and 1t21:22)

course- 6-10% malignant of all primary malignant bone. Age: youngest among malignant bone tumors. Diaphysis of long bones, prognosis is dismal but improved by chemo.

40

Metastatic tumors to bone

metastatic carcinoma, most common malignant tumor of bone. may be blastic or lytic, multifocal or solitary, common Primary sites

BLT and Kosher Pickle
Breast, Lung, Thyroid, Kidney Prostate

Should consider multifocal disease, location (vertebral, diaphysis,), older pateints, pertinent history. biopsy performed to confirm diagnosis when clinical features are questionable, morphology and ancillary studies may confirm site of origin.

41

Multiple myeloma

tibia, can involve the skull and long bone, can present as a primary bone tumor.