Bone Phys/path Flashcards
Inter-medullary callus
- forms new bone from endochonral ossification following hematoma formation
- soft callus -> hard callus
Vascular response in fracture repair
- Bloodflow increased substantially peaks at two weeks
- Angiogenesis and vasodilation increases
Concave/convex remodeling
- convex: electropositive->osteoclast
- concave: electronegative->osteoblast
Contact vs. gap healing
- contact: allows for direct healing with lamellar bone
- gap: 200-500 nm: fill with woven bone, remodeled to lamellar
TGF in bone repair
- induces the synthesis of cartilage specific proteoglycans and type II collagen
- stimulates osteoblasts
BMP in bone repair
- 1,2 and 3
- 1: cleaves carboxy terminus of procallagen I,II and III
- 2: induces endochonral ossification
- 3: potent inducer of mesenchymal -> bone tissue
FGF in bone repair
- acidic (FGF-1), basic (FGF-2)
- proliferation of chondrocytes and osteoblasts
- FGF2 stims angiogenesis
PDGF in bone repair
- I and II
- IGF-I induced by GH in liver
- bone and collagen synthesis, osteoblasts proliferation and inhibits bone collagen degradation
Cytokines in bone repair: IL-1,4,6 and 11, CSF, TNF
- Stimulates bone resorption: IL-1 most potent
- IL-1 and 6 inhibited by estrogen
Prostaglandins in bone healing
- PGEs inhibit osteoclasts and stimulate bone formation
- leukotriens do the opposite
Hormones in bone repair: estrogen, thyroid, glucocorticoids
- estrogen: stimulates fracture healing through IL I inhibitor
- T3/4: stimulat osteoclast resorption
- glucocorticoids: inhibits Ca absorption from gut -> increased PTH -> increases osteoclast activity indirectly
PEMF
- Signals in 20 to 30 Hz range
- Shows efficacy in bone healing
- Bluegray skin and yellow brown microscopic pigment
- Presents with black urine
- Associated with severe early-onset arthritis and spine and lower extremity joints
- Alcaptonuria
- Results from homogentistate 1,2 deoxygenase deficiency -> Buildup of homogentisic acid
Anatomic sequelae of osteoarthritis
- Joint space narrowed
- sclerosis of subchondral
- cystic degeneration of bone
- osteophyte lipping
- chronic pain and debilitation
- Insidious onset of malaise fatigue and generalized musculoskeletal pain
- This is followed by polyarticular joint pain in the hands and then the fee
- RA
- Sequela a: destruction of ligaments tendons joint capsules-> deformities
RA immunopathenogenesis
- HLA-DRB1 assoc
- Activated CD4 stimulates macrophages and B cells
- b cells contribute autoantibodies
- TNF/IL1: Stimulates synoviocytes to make inflammatory mediators/mellatoproteases
Synovium and stroma consisting of inflammatory cells granulation tissue and fibroblasts which grow over articular cartilage
- pannus
- sq: fiberous ankylosis, -> bony ankylosis
Fibrinoid necrosis surrounded by palisading rim of macrophages with no microbial infiltrates
- Rheumatoid nodule
- onset under age 16
- arthritis present for 6 weeks, spiking fevers, malaise
- rheumatoid nodules skin usually absent
- rheumatoid factor usually negative
Juvenile idiopathic Rheumatoid arthritis
- HLA-B27 assoc
- oligoarthritis and tendinitis
- immune-mediated disease
- ankylosing spondylitis
- reactive arthritis
- psoriatic arthritis
- arthritis assoc with chronic inflammatory conditions
- Negatively biferingient crystals
- hyperuricemia
- tophi
- gout/gouty arthritis
Mechanism for hyperuricemia
- 90% due to decreased excretion of uric acid (upregulation of URAT1->increased resorption
HGPRTase deficiency
- overproduction of uric acid due to lacking purine salvage pathway
- Lesch-Nyhan syndrome
Mechanism for acute gouty arthritis
- hyperuricemic conditions addressed by neutrophils which phag the crystals. They aren’t broken down and destroy the neutrophils releasing inflammatory cytokines.
Positive biferingient rhomboid crystals and assoc mutation
- pseudo gout: Calcium pyrophosphate accumulation
- associated with AD mutation of ANKH gene
Infectious arthritis: epidemiology
- H. flu: under age 2
- S. aureus: older kids and adults
- N. gonorrhea: late adolescence and younger adults
- salmonella: sickle cell
-Insidious onset of worsening pain resulting from caseating granulomatous inflammation often times within the spinal column
- osteomyelitis from infectious TB
- Potts disease
- hips>knees>ankles
Arthritis associated with cross reactive Borrelia antigens
- infectious arthritis
- silver stain positive in only 25%
Ganglion cyst
- 1-2 centimeter translucent cyst not communicating with the joint space and has no cellular lining
- excision is curative
Lipoma/liposarcoma Fibromatoses/fibrosarcoma Rhabdomyoma/rhabdomyosarcoma Leiomyoma/leiomyosarcoma Hemangioma/angiosarcoma
- Benign/malignant adipose tumor
- Benign/malignant fibrous tissue tumor
- Benign/malignant skeletal muscle tumor
- Benign/malignant smooth muscle tumor
- Benign/malignant vessel tumor
Lipoma versus angiolipoma
Lipoma: more common, painless, Subcubitus extremities and trunk
- Well differentiated circumscribed adipocytes
Angiolipoma: Male predominance subcutaneous often painful
- Well differentiated adipocytes and capillary sized vessels with thrombi
MDM2 amplification, lack of p53 inhibition
TLS-CHOP
Pleomorphic
- lipoblasts (lipid vacuoles, scalloping nucleus) with atypical lymphocytes
- MDM2: Well differentiated, best prognosis for liposarcoma
- myxoid morphology
- pleomorphic: Liposarcoma with poorest prognosis
- Rapidly expanding subcubitus mass muscle of forearm or trunk
- Immature tissue culture would fibroblasts and myofibroblasts high cellularity
- Nodular fasciitis
Aggravating deforming fibrous lesion in 3 superficial location
- Fascicles of mature myofibroblasts with dense collagen
- Palmer (dupuytrens contracture),
- plantar (ledderhose disease),
- penile (peyronie disease)
Locally aggressive infiltrating disfiguring mass
Associated with deep proximal structures
Long fascicles of bland fibroblasts infiltrating surrounding tissue
Associated with the B-catenin/APC gene
- Desmoid tumor (deep fibromatosis)
- abdominal (anterior wall) extra abdominal, intra abdominal
Infiltrated fleshy masses with hemorrhaging and necrosis
Herringbone pattern of fascicles of malignant spindle cells
- Fibrosarcoma
The most common sarcoma in kids
- Cluster of grapes
- t2;13, PAX3-FOXO1A
- Atypical bizarre tumor cells
Rhabdomyosarcoma
- botryoid and embryonal (best prognosis) bladder, vagina, nasopharynx
- alveolar in extremities, adolescents (worst prognosis)
- pleomorphic
HOXD-13 mutation
- sympolydactyly
FGFR 3 mutation
- achondroplasia
- thanatotropic dwarfism
COL1A1 mutation
Osteogenesis Imperfecta
Synpolydactyly
- HOXD-13 mutation
- Extra third digit and fuse third and fourth
- homeobox genes associated with absent/extra bones and acrodactyly
Decrease of normal chondrocyte proliferation at growth plate
Achondroplastic dwarfism
Osteogenesis Imperfecta types
Defective synthesis of type I collagen: too little bone density
- type I mild: normal lifespan
- type II: non-survivable
- type III/IV: moderate severity, deforming
Osteogenesis imperfecta morphology
- commonly shin deformations and scoliosis
Deficiency of lysosomal acid hydrolase enzymes that degrade mucopolysaccharides
- progressive accumulation in cells
- hurlers: type I MPS, deficiency of a-L induronidase
- hunters: type II MPS, deficiency of iduronate-2-sulfatase;
XL recessive
Long bones lacking normal medullary cavity filled with persistent primary spongiosa
- Fractures pancytopenia and cranial nerve deficits
- osteopetrosis “marble bone” disease
- very heaped but very brittle bones
- type II Carbonic anhydrase deficiency
- May also have renal tubular acidosis
Mosaic pattern of lamellar bone in axial skeleton/femur
Increased ALPase
Increased osteoblast/osteoclast
Predominantly whites
- Paget’s disease
- sqstm1 mutation in 50%
- abnormal bone architecture
Osteoclast signaling
- RANK binds and MCSF is released with osteoprotegrin from stromal cell/osteoblasts
- causes release of NFKB in monocyte osteoclast precursor
- OPG binds and inhibits RANK
A specific and sensitive marker for osteoblast activity
- osteocalcin
Osteogenesis imperfecta
- AD (primarily)
- type I collagen defect (COL1A)
- type I (mild) type II (lethal) type III/IV (moderate to severe, deforming)
- Short stature, chest wall abnormalities, bone malformations
- a-L induronidase
- indurate-a-sulfatase
- hunters and hurlers
- mucopolysaccharide accumulation
- dense, brittle bones
- concurrent renal tubular acidosis
- pancytopenia -> Extra medullary hematopoiesis
- carbonic anhydrase II deficiency -> osteopetrosis (marble bone disease)
- decreased osteoclast activity
Genetic factors and developing osteoporosis
Estrogen receptor, vitamin D receptor and LRP 5
Severe complications of Paget’s disease
- Giant cell tumors, sarcoma (osteosarcoma/Fibrosarcoma)
- 5-10% in people with polyostoic disease
Vitamin D deficiency in kids
Deformed bones
Ricketts,
In adults it’s osteomalacia
Severe cortical bone defect: increased bone resorption
Dissecting trabeculae on X-ray
Brown tumor
- hyperparathyroidism
- can result in osteitis Fibrosis cystica if untreated
- brown tumor not actually tumor: microinfarcts and 2nd hemorrhages
- Increased bone resorption
- delayed matrix mineralization
- growth retardation
- osteoporosis
- metabolic acidosis
Renal osteodystrophy
- Phosphate retention due to renal failure results and secondary hyperparathyroidism (phosphate is a secondary regulator of PTH: PTH blocks resorption of phosphate in tubules normally leading to excretion, so with increased phosphate more PTH is needed to induce -> too much resorb)
- decreased vitamin D conversion
Wedge shaped infarcts in medullary bone
- subchondral infarcts
- cortical bone not usually affected by infarcts due to the periosteal collateral circulation
Pyogenic osteomyelitis
- H. Fu: kids under 2
- S. aureus: kids and adults
- N. gonnoreae: adolescents and young adults
- salmonella: HbS
Typically hematogenous spread: ots. Tuberculosis increasing
Osteomyelitis clinical course
- a necrotic center known as a sequestrum forms inside of the involucrum
- may form a communicating nidus to drain through the soft tissue
Osteomyelitis localized to the jaw
- sclerosing osteomyelitis of Garre
- HLA B27 to susceptibility
- Destruction of sacroiliac and apophysial joints
- ANA seronegative
Ankylosing spondylitis
- B 27 Cw6 susceptibility
- Psoriatic condition associated with axial joints and enthesis
Psoriatic arthritis
Finkelstine test
- adduction of wrist with thumb adducted causes pain over radial styloid process
- DeQuervains tenosynovitis
Yergasons sign
Bicipital tendinitis: Anterior shoulder pain
Shoulder pain with full range of motion
- Olecranon bursitis not involving the joint itself
Capsulitis arthrogram
- Reduced uptake of die on MRI
Pain in shoulder with abduction of arm from 60-120°
- Rotator cuff tendinitis: Most commonly weakness of the supraspinatus tendon -> Impingement of supraspinatus between humeral head and acromion process
Typically healthy young person with inability to abduct the arm at all
- Supraspinatus tendon tear
Morphological changes in osteoarthritis
- thickened joint capsule, synovial hypertrophy
- sclerosed subchondral bone
- cyst formation
Bouchards and heberdens nodes
- B before H in osteoarthritis
- B=proxymal
- H= distal
Gullwing deformity on X-ray
- Indicative of osteoarthritis
RA vs OA in hand
- OA spares MCP joints, RA does not
- RA is disfiguring, not just inflammatory
Boutonnière and swan neck deformities
- Both due to contracture of muscle groups in the hands in rheumatoid arthritis
Extra-articular features of rheumatoid arthritis
- pleuritis
- pulmonary nodules
- interstitial lung disease
- Caplans syndrome
~ lung nodules
~ pneumoconiosis
~ RA
RA, splenomegaly, granulocytopenia
Feltys syndrome
Scleromalacia perforans
- complication from RA
- thinning of sclera result in extrusion of intra occular contents
Caplans syndrome
~ lung nodules
~ pneumoconiosis
~ RA
Jaccouds vs. SLE arthropathy
Both are symmetrical and nonerosive but SLE is nondeforming unlike jaccouds
SLE trt
- avoidance of the sun
- hydroxychloroquine
- steroids
- cyclophosphamide/mycophenolate mofetil
SSA Ro/La
ANA sp to sjorgens syndrome
Calcinosis, Raynaud’s phenomenon p, esophageal dysmotility, sclerodactyly, telangiectasia
- crest syndrome assoc with scleroderma (limited cutaneous)
Can’t see, can’t pee, can’t tree
- conjunctivitis, urethritis, arthritis
- triad of reactive arthritis
- typically oligoarthritis
Treatment for reactive arthritis
Abx if infection is still present
NSAIDs
Corticosteroids
DMARDs: sulfalazine, methotrexate, anti-TNFa
Keratoderma blenorrhagica
- identical to pustular psoriasis
- variable prognosis
Enteropathic arthropathy trt
- NSAIDs are a problem
- sulfasalazine
- TNFa inhibitors
Hyperuricemia levels
- M: 7.1mg/dl
- F: 6.0 Mg/dl
Precipitants of gout and gouty arthritis
- drugs: Diuretics, heparin, cyclosporine
- trauma
- EtOH
Disease states associated with CPPD crystals
- Hypothyroidism, Hyperparathyroidism,hypophosphatasia, hemochromatosis, hypomagnesemia
Vasculitis affecting large and medium blood vessels
- giant cell arteritis
- takayasu’s arteritis
- angiitis of CNS
Vasculitis affecting predominantly medium and small blood vessels
- polyarteritis nodosa
- microscopic angiitis
- Wegeners syndrome
- Churg-straus syndrome
Vasculitis affecting predominantly small blood vessels
- Henoch-schonlein purpura
- HSN vasculitis
- mixed cryoglobinemia
- medium/small vessels
- Identified by recent history of severe asthma, eosinophilia, sinusitis, pulmonary infiltrates, G.I. ischemia
Churg straus vasculitis
- Small/medium vessels
- ischemia involving
~ renal, GI mesentery, peripheral nerves, CNS - livedo reticularis (doily rash)
Polyarthritis nodosa
Angiogram demonstrating aneurysmal dilation tapering a blood vessel
Diagnostic for polyarteritis nodosa
- Headache, scalp tenderness, fever, weight loss, night sweats, visual disturbance, blindness
- Vasculitis involving cranial arteries and large branches aorta
- Giant cell arteritis (temporal arteritis)
- trt with high dose steroids
Wegeners syndrome
- Radiographically identical to metastatic carcinoma of the lung
- get a biopsy
- saddle nose deformity
Henoch schonlein purpura
- classic triad:
~ lower extremity rash
~ abdominal pain
~ hematuria
