Musculoskeletal Domain Overview

Condition Diagnose It Pathophysiology Pathology Clinical Course Genetics/Epi Treatment The motor unit made up of: Lower motor neuron (Cell body + Axon) + NMJ + Skeletal muscle innervated by motor neuron Peripheral nerve structure: o Epineurium surrounds many fascicles Fascicles: Contain Axons (Unmyelinated, Myelinated), Myelin made by Schwann Cells Endoneurium = CT around axons Surrounded by Perineurium o Fiber diameter/number normally have a bimodal population in terms of diameter of fibers. This bimodal distribution is disrupted in peripheral nerve disease o Skeletal Muscle: Mm fibers are multinucleated syncytium nuclei are at periphery mostly. Reserve cells at periphery regrow skeletal mm when damaged (less of this in cardiac mm) o Types of skeletal mm: Type 1: Red, slow twitch, sustained action, high in oxidative enzymes, (aerobic), many mitochondria, abundant fat more lipid metabolism happens here Type 2: White, fast twitch, sudden action, low in oxidative enzymes, (anaerobic), few mitochondria, little fat, susceptible to disuse Nerve innervating muscle fiber determines type Characterization: ATPase stain: Low pH Type 1 dark, Type 2 light A little higher: can distinguish Type 2B from 2A (type 2B most vulnerable to disuse) High pH Type 1 light, Type 2 dark o Pathology: Atrophy, necrosis, regeneration, hypertrophy, denervation, fibrofatty replacement SMA 1 Acute infantile (Wednig-Hoffman) floppy baby sx Chromosome 5 (SMN gene in 98%). Contiguous NAIP gene associated w/severe SMA 2 Chronic infantile phenotype SMA 3 Kugelberg-welander Short internodes, thinly myelinated axons Seen with HMSN (Hereditary Motor Sensory Neuropathy =Charcot Marie Axon intact, often begins Spinal roots involved Tooth), CIDP(Chronic Inflammatory Demyelinating Polyneuropathy) at nodes of Ranvier No denervation atrophy, possible disuse atrophy Ex: Guillain-Barre, CIDP, HMSN (Charcot-Marie-Tooth) Onion bulbs with chronic, repeated episodes of de/remyelination Wallerian degeneration axonal degeneration distal to axotomy Sprouting an attempt to establish connection with distal stump. If established, regrowth at 1-2 mm/day. Ex: Toxic diseases (organic solvents, Destruction of axon plus Traumatic neuroma mass lesion can form, can be painful. organophosphates, heavy metals, myelin sheath Neurogenic atrophy of skeletal mm if motor nerve vascular disease) Chromatolysis (nissl substance pushed to periphery) in motor neuron cell body with axotomy Chronic inflammation, segmental Ascending paralysis, slowed nerve Campylobacter jejuni is most Polyradiculoneuropathy Immune-mediated, likely initiated by infection demyelination conduction velocity common implicated organism Polyradiculoneuropathy Lab = NCV and CSF changes like GBS (slow nn conduction, cytoalbuminologic dissociation). Symmetrical proximal and distal weakness. Chronic inflammation, onion bulbs with repeated attacks. Clinical presentation resembles Guillain Barre, but less acute/longer sx duration, less frequent recovery, Relapses/remission in about .

Muscle physiology Review (lecture)

Spinal muscular atrophy Segmental demyelination

Axonal degeneration

Guillain-Barre Chronic Inflammatory Demyelinating Polyrad. HMSN-1 (CharcotMarie-Tooth): Diabetic Neuropathy

Polyradiculoneuropathy Polyradiculoneuropathy

Peripheral myelin protein 22 (PMP-22) mutations (usually 17p11.2 duplication) account for Hypertrophic nerves, inverted 90%. Function of protein is unknown. 20% have significant disability, 20% asx. champagne bottle legs Others have HMSN1b or X-linked forms (connexin 32). Axonopathy, demyelination, or both. CSF protein Symmetrical distal polyneuropathy (stocking/glove), autonomic neuropathy (orthostasis, impotence, GI motility problems), often elevated. mono neuropathy or mononeuropathy multiplex (motor or sensory, LS plexus, femoral nerve have prominent atrophy).

Condition

Diagnose It

Pathophysiology

Pathology o o o o o o o o o o o o o

Skeletal Muscle Plasticity in Health and Disease

5 basics things to know: o Muscles are controlled by nerves Skeletal mm cells are run by neurons: Motor unit = 1 neuron + many mm cells 1 to 1 AP transmission at neuron-muscle synapse (NMJ = endplate) Skeletal mm APs: Ionic basis: as in motor neuron depolarization due to fast voltage-gated Na+ channel, repolarization due to fast voltage-gated K+ and Cl- channel Conduction velocity along fiber very fast (~5 m/s large diameter) Relatively long spike duration and delayed repolarization due to t tubule system Time course of AP, Ca, and force AP: 1-2 ms Ca: peak 5-10 ms Force: peak 20-60 ms Ca transient normally big enough for full activation in a single twitch Force rise time and peak twitch force depend on: Vmax (internal shortening to stretch series elasticity) and Duration of Ca transient Frog experiment: Twitch: mechanical response to single AP Tetanus: response to high frequency APs (twitch/tetanus force ratio ~0.2-0.25) Isometric no shortening allowed Isotonic shortening with constant weight Skeletal mm force is controlled by CNS, largely by variations in motor unit recruitment, motor unit firing rate NOT by varying cytoplasmic calcium. Skeletal mm cells should just do what they are told! o Muscles are strong Force*length = constant think physics mm have to be super strong to lift something! Force-velocity curve: External work = force*distance; Power = work/time = force * velocity o Muscles are big and packed with proteins: Size: Diameter = 20-50 u; Length = up to 30 cm; Multinuclear cells. Dont divide, but can grow with addition of satellite cells o Not all muscles are the same in physiology and biochemistry the slower you get, the more efficient you are in terms of ATP use IIB: Fastest, use most ATP, Glycolytic metabolism, white color, fatiguable, large IIA: Fast, high ATP use, mixed glycolytic/oxidative metabolism, red color, not bad in fatiguing, medium size I: slow, low ATP use, oxidative metabolism, red color, more endurance, small Cardiac and Smooth: even slower, use even less ATP o Exercise changes muscle phenotype (they have plasticity) endurance, strength, size Studies of plasticity usually perturb mm workload/rate over protracted periods of time Innervation determines fiber type Sustained activity causes exercise capacity. mitochondria, changes in Ca handling, and myosins, altered glucose transport/metabolism loading causes in mm mass existing fibers and new fibers may develop (satellite cells), Ca handling and metabolism altered activity or loading causes mass myofiber dimensions

Clinical Course Genetics/Epi Treatment Altering ATP homeostasis Results in Phenotype Restructuring Changes in pattern of activity alter phenotype = mechanical + metabolic Changes in metabolism with same activity alters phenotype Potential sites of action: Direct modulation of genome expression by energy metabolism OR Operates at physiologic level to alter common signal pathway Calcium homeostasis modulates function and phenotype and is sensitive to cellular energetic status (ADP, ATP, etC) Physiologic signals: Calcium cycling, Energy charge, REDOX, Mechanical strain Loading is important for homeostatic control of mass: mTOR involved in hypertrophy can modulate by lifting Ubiquitin linked to atrophy Atrophy: Happens naturally (bedrest), antigravity, lack of use Loss of Ca and ATP Free Energy homeostasis results in disease pathology MM damage: Appears brighter in MR (up to 4 days later) Satellite cells: Add mm mass in loading and injury

Condition Myopathies (Inflammatory)

Diagnose It

Pathophysiology

Neurogenic atrophy = fiber atrophy, fiber type grouping, grouped atrophy, absence of inflammation.

Pathology Clinical Course Inflammatory myopathy = lymphocytic infiltrates, fiber degeneration and necrosis (pale pink), fiber regeneration bluish w/large vesicular nucleus, nucleolis Endomyseal T cells CD8 infiltrates lead to necrosis, followed by regeneration

Genetics/Epi

Treatment

Can get trichinosis, bacterial infections of fascia/skeletal mm (but not focusing on this for the domain) Women 40-60

Polymyositis

EMG = purely myopathy CPK = high (up to 50X)

Myopathic weakness

Risk of malignant neoplasms (esp lung cancer)

Myopathic weakness Rash/calcinosis is present Dermatomyositis EMG = purely myopathy CPK = high (up to 1050X) Perivascular/perifascicular infiltrates, perifascicular atrophy CD4 and Bcell mediated. Heliotrope eyelids Rimmed vacuoles, amyloid-like (nonbranching, + w/Congo red), filamentous inclusions (w/Amyloid beta, phosphorylated tao, ubiquitin, prion protein)

Women 40-60 Risk of malignant neoplasms (esp lung cancer)

Inclusion body myositis

EMG = myopathy +/neurogenic component CPK = high (not as high as PMS)

Myopathic weakness, but sometimes distal weakness is prominent

Disorders of the NMJ Ptosis (most common initial finding). Autoab against Ach receptors (Type II HS rxn) Ab inhibit/destroy receptors Ab synthesized in thymus 85% have thymic hyperplasia w/germinal follicles Fatigue without soreness or burning Dysphagia for solids/lipids (in striated mm of upper esophagus) LambertEaton Syndome No reversal of sx with AchE inhibitors alone Auto ab to presynaptic Ca channels Proximal mm weakness Symptoms improve with muscle use! Associated with paraneoplastic diseases (small cell lung cancer) Mm weakness improves w/rest Men in 60s/70s Women in 20s/30s d risk of developing thymoma (15%)

Myasthenia Gravis

Tensilon (edrophonium test) Inhibits AchE (d Ach reverses mm weakness)

Condition Muscular Dystrophies

Diagnose It Wide variation in fiber diameter, Lab: Serum CK 1st 10 yrs, declines as muscle degenerates Western blot Duchenes - NO dystrophin, Becker thinned bands.

Pathophysiology excessive ENDOMYSIAL FIBROSIS

Pathology fiber degeneration and regeneration, Type 1 AND 2 fibers involved Varied fiber size (small and enlarged fibers with fiber splitting); internalized nuclei, Degeneration, necrosis/phagocytosis of mm fibers, mm fiber regeneration. Proliferation of endomyseal CT. Mm eventually almost totally replaced by fat ENDOMYSIAL FIBROSIS May also have pathological changes in heart (HF, arrhthmias can develop) CENTRAL NUCLEI No CNS problems established, but cognitive component of disease

Clinical Course

Genetics/Epi

Treatment

Normal at birth, early milestones met Walking often delayed, pt is clumsy/unable to keep up with peers Sx around 2-5 yrs: Weakness/wasting of pelvic muscles is 1st Child places hands on knees to help stand, Gowers sign (tripod), X-linked recessive Xp21, but 1/3 are new mutations Most severe, most common type (1:5,000) Female carriers have d serum CK Myostatin TGFB protein inhibits mm growth loss causes hyperplasia during development and hypertrophy throughout life WONT fix the problem making the mm stronger will make them rip apart faster. IGF-1 influences mm mass too.

Duchennes Muscular Dystrophy

Dystrophin deficiency (normally anchors actin to membrane glycoprotein and attached to sarcoglycans I/M band associated, possible role in maintaining myocyte membrane integrity w/contraction). Dystrophin deletions, point mutations w/frameshift. Progressive degeneration of Type I/II fibers causes infiltration of muscle tissue by fat (Pseudohypertrophy of calf) Affects PROXIMAL mm and calves

Waddling gait Wheelchair by 12 Death by 20 from diaphragm mm failure (pulmonary infection, cardiac decompensation, resp insuff)

Becker Muscular Dystrophy d serum CK

Dystrophin is defective (Normally dystrophin transfers force of contraction to CT) Myotonia= sustained involuntary contraction of a group of mm (especially subsequent to voluntary contraction or irritation) Above = spontaneous mm discharge w/needle insertion Myotonic dystrophy = defective splicing of muscle C1C1 channel mRNA caused by nuclear accumulation of CUG or CCUG repeat RNA (most common human dystrophy) Dystrophila myotonia protein kinase mRNA affected Selective atrophy of Type I fibers (early on)

Sx not as extreme as Duchennes

X-linked Xp21 1:20,000 Facial weakness, myotonia (worse w/maternal inheritance), frontal balding, cateracts, testicular atrophy, cardiac involvement

(Other forms of MD AD or AR, different presentations)

Myotonic Dystrophy

Can elicit myotonia by percussing thenar eminence

Variation in fiber size d internal nuclei (in chains) Ring fiber: sub-sarcolemmal band of cytoplasm, has myofibrils around longitudinally oriented fibrils. Sarcoplasmic mass may come out from ring (stain blue in H&E)

AD most common adult muscular dystrophy (TNT repeat disorder) can have anticipation.

Pt complains of difficulty releasing grip,

Condition

Diagnose It Physical exam: Straight leg raising (80% se, 40% sp), Contralateral leg raising (90% sp, 25% se), one on its own not that great but put them together and they are helpful.

Pathophysiology Non-inflammatory rheumatoid pain Possible causes: herniated disc, disc disease, spondylolisthesis, spondylolysis, facet sx, spinal instability, radiculopathy, fibromyalgia, myofacial pain sx, somatic dysfunction, sacroiliac joint pain, CT disease, arachnoiditis, fractures, spinal stenosis, tumor, infection, osteoporosis, lumbar strain, visceral/operant/central pain, Pagets, Scheurmanns, Job satisfaction, psychogenic pain, malingering, short leg sx, unlevel sacral base Boeing study: Psychological, Work satisfaction, and history of low back pain were most predictive Acute low back problems in adults: activity intolerance due to back related symptoms, over age 18, lasts < 3 mo. Evidence - some care is inappropriate disability despite tx. Spinal fusion not recommended,

Pathology Initial evaluation: look for red flags o Cancer (age>50, previous cancer, wt loss, >1 month pain w/tx, no relief w/bed rest, fever) o Osteomyelitis (IV drugs, UTI, skin infection, fever, immunocomp), Sciatica o Cauda equina syndrome (bladder/bowel, saddle anesthesia numb by butt, limb mm weakness).

Sed rate and CBC - labs for suspected tumor Back Pain (mechanical) X-rays: not recommended in 1st 4 weeks if no red flags Reflexes:DTR/MSR/my otatic reflex o 0=absent, o 1=trace, w/ reinforcement, o 2= lower of normal, o 3=upper of normal, o 4=abnormally brisk, Note clonus separately

Clinical Course o Spinal stenosis: pseudoclodication pain in legs while walking often relieved by leaning forward or sitting not due to peripheral vascular disease. Dont donsider in 1st 3 months. Relief with leaning forward (shopping cart sign), age>50

Genetics/Epi

Treatment

Assess non-spinal causes for LBP rectal, UTI Low back- 60-90% lifetime incidence, 5% annual incidence, 5-25% incidence lower back pain, 40% get sciatica 50% recover in 1 month, people get recurrence Chronic (10% - get 80% of cost) Questions to guide tx: What activities cant you do? What tx have you tried? What do you do to stay in shape? What medications have you tried? What want vs expect from tx? NSAIDs, Tylenol, Benzodiazepams (same as NSAIDs except drowsy), Not helpful: Steroids, Bed rest, Facet injections, epidurals without radiculopathy, opioids (and if used, only short-term)

Ankylosing spondylitis: onset <50, not relieved in supine position, morning stiffness, pain>3 months Sciatica: if activity restrictions >1 month or clear clinical; electrophyscompromise, correlating imaging can refer to surgery.

Condition

Diagnose It

Pathophysiology

Pathology

Clinical Course

Genetics/Epi

X-ray: Not reliably detected until ~35% loss Bone Density Test: DXA scan (dual-energy absorp typically check every 2 yrs), quant CT (less commonly used)

Definition: skeletal disorder characterized by compromised bone strength predisposing a person to d fracture risk. Peak bone mass: by 30, det by: hereditary (vit D receptor, collagen 1A1, estrogen receptor, ILGF-1), Physical activity, muscle strength, diet, hormonal state Bone loss: ~0.7% annually. Influences: Age (senile osteoporosis): osteoblasts replicate less, proteins bound to ECM lose biologic potency; Physical activity: mechanical force needed to stimulate growth Genetic factors: Vit D receptor (~80% of peak mass variation); Nutritional state: Ca, vit D Hormones: PTH, Estrogen (causes Il-1/6, TNF more osteoclast activity. Osteoblasts cant keep up)

porosity of skeleton from bone mass/density. Uncoupling of osteoblast vs osteoclast activity. d thickness of cortical and trabecular bone. Post-menopausal: tend to have vertebral fracture (lose height, lumbar lordosis, kyphoscoliosis) d risk of future fracture Femoral neck/pelvis/spine fractures: cause pulmonary embolism, pneumonia (~45,000 deaths/yr) Localized (diffuse osteoporosis of limb) or systemic (metabolic bone disease). Generally asx until fragility well advanced Colles (distal radius)

Treatment Estrogen replacement tx helps prevent post-menopausal loss. Prevention: exercise (wt bearing swimming doesnt help), Ca/Vit D intake, estrogen replacement, biphosphonates (inhibit bone resorption), calcitonin (inhibits osteoclasts), recombinant PTH (stimulates formation of bone in amounts > reabsorbed) Eeduce sedating meds, tx dementia and vision problems Adult <50 need 1,000 mg Ca and 400-800 IU vit D daily Adult >50 need 1,200 mg Ca and 800-1000 IU vit D daily Bone completely remodels in 18 months

Tscore

( PtBMD YoungAdult MeanBMD) (1SDofYoungA dultMeanBM D)

34 million at risk (osteopenia) 10 million have osteoporosis 1.5 million new fractures each year Most common metab abnormality of bone Primary cause (most common) = senile, postmenopausal. Women: 1/2 over 50 have osteoporotic fracture (only 25% men!)

Osteoporosis

# of standard deviations from mean compared to young adult. Normal = -1 or above Osteopenia= -1 to -2.5 Osteoporosis: -2.5 or below Severe Osteoporosis= -2.5 or below with fragility fracture Use lowest to dx forearm, hip, femoral neck, spine
Zscore
( PtBMD AgematchedBMD ) (1SDofAgeMat chedMeanBM Ding / cm 2 )

low Z score (<-2.0) means pt >2 SD below mean Serology: blood Ca/PO4/alkaline phosphatase level NOT diagnostic tend to use in pt <50, kids

Fragility (insufficiency) fractures: fall from standing height or less/without trauma (33-50% of women, 15-33% of mens w/age). Typically hip, spine, wrist **Diagnostic even if normal mineral density** Risk: Non modifiable: age, female, asian/Caucasian, previous fragility fracture, family hx of osteoporosis, small frame Modifiable: estrogen deficiency, body wt<127, Low Ca/Vit D intake, Inadequate physical activity, excess alchohol, smoking, drugs (anticonvulsants, glucocorticoids, excess thyroid replacement)

Secondary Causes

Long-term glucocorticoid tx: bone mass by bone resorp, bone formation on cortical/trabecular surfaces

Space travel: bone stress (which is needed to stimulate remodeling) Prevention: educate parents, coaches of impact on athletes. Discuss at pre-participation sports physical. Any visit for stress fracture, wt change, disordered eating, amenorrhea, bradycardia, arrhythmia, depression **any female athlete missing 3 consecutive periods or has intervals >35 days apart should be evaluated by physician Tx: lifestyle changes, dietary changes (see dietician), get goal wt (above 127, gain 0.5-1 lb per week until goal), activity 10-20% (dont have to stop), monitor wt every 2-3 months. Ultimate goal is to return normal menses through lifestyle changes, proper nutrition, revised training regimens, wt gain. Estrogen (estrogen-containing oral contraceptives or cyclic estrogen & progesterone). s BMD Ca 1200-1500 mg per day (for ages 11-24), Vit D 400-800 IU If severe disorder or depress, then psychological eval to consider SSRI No drug approved for pre-menopausal females Biphosphonates can affect fetal bone development and have long biologic half life best avoided in females who may become pregnant someday

Early signs of disordered eating fatigue, anemia, electrolyte imbalance, depression Female athlete triad: Disordered eating, amenorrhea, osteoporosis Amenorrhea (rule out other treatable causes) DXA scanning: Lack of evidence in use (young female may not have reached peak bone mass yet). Z scores may be helpful (compare to average age, race, sex). Z score <2.0 (below expected for age)

Age: Typical age of young athlete coincides with important time of building bone Diet: Eating disorder can result in low Ca and vit D and prevent reaching peak bone mass. May lead to irreplaceable bone loss Hormones: Low estrogen results in accelerated bone loss. Excessive training and stress from malnutrition can cause changes in hypothalamus (hypogonadotropic hypogonadism) leading to d estrogen levels. Low estrogen leads to amenorrhea, eventually bone loss (estrogen antiresorptive) o Amenorrhea: o Primary: No spontaneous bleeding by age 16 o Secondary: 6 month absence of menstrual bleeding with prior hx of regular menses o Both can result from hypothalamic dysfunction from excessive exercise and eating disorders

Poor bone quality can result in stress fractures, risk of other fractures Although most women w/ the triad dont fit criteria for anorexia or bulimia, they have greater risk of mortality than general population Prevalence unknown amenorrhea is more common, but not normal in female athletes. Amenorrhea occurs in up to 66% of female athletes and 2-5% of general population. Studies have reported disordered eating in 1562% of female college athletes (restricted food intake, vomiting, diet pill/laxative abuse) Risk: frequent weigh-ins, punitive consequences for wt gain, overly controlling coach/parent, high risk sports (gymnastics, figure skating, ballet, distance running, swimming, diving) Why? Performance improvement (runners), competitive thinness (gymnastics, figure skating), weight categories (rowing, martial arts), revealing sports attire (swimming, volleyball, track and field)

Condition

Diagnose It Pathological fractures at birth

Pathophysiology

Defective synthesis of Type 1 collagen

Pathology Too little bone osteoporosis w/cortical thinning, attenuated trabeculae, skeletal fragility

Osteogenesis Imperfecta (Brittle bone disease)

Blue sclera (reflection of underlying choroidal veins), deafness

Clinical Course Type 1: acquired mutation lots of fractures early on (less into puberty), blue sclerae, hearing loss, dental imperfections

Genetics/Epi AD inheritance Type 2: lethal form, fatal in utero/in neonatal period. Incidence = 1:10,000

Treatment

Exercise, pain medicine, physical therapy, wheelchairs, braces, surgery. May be confused with child abuse

Osteomalacia, rickets

Disorganized bone remodeling . Contours not affected, but bone is weak (especially vertebral bodies, femoral necks). Osseous function: Strength, cushioning, mobility, endocrine, Ca/Vit D dependent Diaphyseal (cortical)=for stability Metaphyseal (cancellous) =cushioning Types of bone: o Lamellar bone: fibers in parallel layers. Structure (see picture below) Trabeculae in direction of stress o Woven bone (nonlamellar) randomly oriented collagen. Weaker. Usually remodeled to lamellar. Seen at sites of fracture healing, attachment, pathology

Adult Vitamin D deficiency causes less intestinal absorption of Ca/PO4, PTH will stimulate loss of Ca from bone to restore blood levels. In kids, it leads to rickets. Bone composition: o Cells: o Osteocytes: in lacunae, Reg bone metab (response to stress/strain), o Canaliculi: canals, contain osteocyte cell processes, preosteoblast-osteocyte connection (probably for response to mechanical, chemical factors) o Osteoblasts: from mesenchymal stem cells. Line surface of bone, produce osteoid. o Osteoclasts: Get rid of bone, from hematopoietic scs, multinucleated, in Howships lacunae. PTH stimulates receptors on osteoblasts to activate osteoclastic resorption. o Extracellular matrix: o Organic (35): 90% type I collagen, also osteocalcin, osteonectin, proteoglycans, glycosaminoglycans, lipids (ground substance) Inorganic (65): hydroxyapetite

Histological: thickened matrix with normal trabeculae. Eventually, difficult to differentiate from other osteopenias. Mechanisms of bone formation: o Cutting cones: to remodel bone. Osteoclasts at front remove, Osteoblasts behind lay down new o Intramembranous (periosteal) formation: long bone grows in width. Osteoblasts lay down seams of osteoid. Doesnt involve cartilage precursors. o Endochondral formation: long bone grows in length osteoblasts line a cartilage precursor. Chondrocytes hypertrophy/calcify ( O2). Vascular invasion of cartilage ossification ( O2 triggers calcification) Growth Factors: TGF (transforming growth factor): precursors (osteoblasts, osteoclasts, chondrocytes); endochondral & intramembranous formation ; synthesis of cartilage proteoglycans, type II collagen; collagen synthesis by osteoblasts.

NOT the same as osteoporosis, because osteoporosis is caused by production of osteoid, while osteomalacia is poor formation of bone in remodeling.

Give biphosphonates to prevent bone loss Renal failure can lead to osteomalacia ( cant convert Vit D to active form in kidneys to absorb new Ca)

Bone physiology

BMP (Bone Morphogenetic proteins): cell differentiation; BMP-3 (osteogenin) mesenchymal differentiation bone; endochondrial ossification (BMP 2/7 in segmental defects); Regulates ECM production (BMP 1 cleaves carboxy termini of procollagens I-III) Fibroblast Growth Factors: 2 Forms: Acidic (FGF-1) & Basic (FGF-2) chondrocytes, osteoblasts, callus formation, FGF-2 angiogenesis

Platelet-derived growth factor: bone cell growth ( Type 1 collagen synthesis by # of osteoblasts). PDGFBB bone resorption by # of osteoclasts Insulin-like Growth factor: IGF I production in liver by GH. collagen & matrix synthesis, osteoblast replication, bone collagen degradation.

Cytokines (IL1/4/6/11) resorption (IL1!) IL1/6 by estrogen (assoc w/ postmenopausal resorption?) PG: osteoblastic formation, osteoclasts. LT: osteoblast bone formation, capacity of osteoclasts to form resorption pits. Estrogen: fracture healing, modulates release of IL-1 inhibitor Thyroid hormones: T3/T4 osteoclastic bone resorption Glucocorticoids: Ca absorption from gut (causes PTH more osteoclast bone resorption)

CK IL-1 TNFa TNFb TGFa TGFb PDGF IGF-1 IGF-2 FGF

form + + + -++ ++ +++ +++ +++

resorb +++ +++ +++ +++ ++ ++ 0 0 0

Condition

Diagnose It

Pathophysiology Direct vs indirect healing Direct: no motion at fracture site (doesnt form callus). Cutting cone is formed, crosses fracture site. Osteoblasts lay down lamellar bone behind the osteoclasts (form secondary osteon). Slow process ~18 months. Direct contact allows healing gap <00-500 microns filled w/woven bone, larger ones filled with fibrous tissue = non-union Indirect: fractures not rigidly fixed. Bridging periosteal (soft) callus and medullary (hard) callus re-establish structural continuity. Callus undergoes endochondral ossification (4-6 weeks) Prerequisites to heal: Blood supply: Nutrient a (intramedullary normal supply for cortex, enters long bone via nutrient foramen, forms medullary aa down the bone), Periosteal vessels (from periosteum, supply ~20% of cortex, but more when injured medullary supply), Metaphyseal aa: in fracture, external supply becomes more important than internal supply

Fractures (healing)

Classification: Complete vs incomplete Closed (simple): skin tissue intact Compound: skin not intact Comminuted: bone splintered Displaced: ends of bone at not aligned Pathologic: break in a bone already altered by disease Stress fracture: slowly developing following physical activity with new repetitive loads (boot camp) Harris lines (Pediatric pts - look like growth ring on a tree happen in stress from temporary slowdown of normal longitudinal growth). 610 weeks after fracture.

Pathology Stability: Early: promotes revascularization, After 1st mo: loading promotes callus formation, healing. Inadequate stabilization: deformation at site, tissue bone (soft callus). Over stabilization: periosteal bone formation (hard callus) Stages of healing First week: Inflammation: Hematoma fills fracture gap, surrounds area. Fibrin mesh seals fracture site, framework for growth. Platelets/inflam cells: PDGF, TGF-B, FGF activate osteoprogenitors stimulate osteoclast/blast (antiinflammatory meds healing!) Soft tissue callus/procallus formed no structural rigidity to bear weight, anchors together 2nd/3rd week (if uncomplicated) Osteoprogenitors deposit subperiosteal trabeculae of woven bone (perpendicular to cortical axis, in medullary cavity) Endochondral ossification of cartilage line bony callus Early callus has excess fibrous tissue/cartilage/bone most volume at concave portion

Clinical Course Mature callus resorbs portions not physically used changes until outline of fractured bone is back, medullary cavity is restored *Wolffs law * bone is restructured in response to stress and strain Problems: Displaced/comminuted can have deformity (and slow splintered bone has to be resorbed 1st) Poor immobilization: callus cant form Nonunion w/motion along gap: central callus has cystic degeneration, luminal surface lined by synovial-like cells (pseudoarthrosis false joint) fix by removing soft tissues, stabilizing fracture site Infection: (comminuted/open): have to eradicate before union Low Ca/PO4, Vitamin Deficiencies, Systemic infection, Diabetes, vascular insufficiency

Genetics/Epi

Treatment

Most common pathologic conditions of bone Bones cant bear weight until mature callus forms after 3rd week + Children/young adults can anticipate perfect reconstitution. Pediatric tend to fracture through hypertrophic zone. Older tend to have pathologic fracture (osteoporosis, etc) repair less, need mechanical immobilization for healing

Immobilize, ensure proper alignment, eliminate infections that block healing Local anatomic factors that influence fracture healing: malnutrition (less activity/proliferation of osteochondral cells, less callus formation), smoking (inhibits osteoblasts, vasoconstriction), DM (collagen defects and poor construction) Electromagnetic field: in vitro bone deformation produces piezoelectric currents, stimulates bone healing (need negative charge for bone to grow) Physeal injuries heal in half the time it takes for nonphyseal fractures to heal in the same area.

Salter-Harris Classifications of Pediatric Fractures

Avascular necrosis

Type II most common! Buckle/Torus Fracture compression failure; usually at metaphyseal/epiphyseal junction. Radiograph: bone Medullary infarct: Cancellous density MRI is most bone/marrow affected, not cortex sensitive test (collateral blood flow). All bone necrosis caused by Subchondral infarct: ISCHEMIA (microcirc disrupted) Where? triangular/wedge-shaped tissue from Mech vasc interruption (fracture) Femoral head (hip) subchondral bone plate to epiphysis Corticosteroids think fracture in (tip). Dead bone has empty lacunae Thrombosis/embolism (N bubbles) elderly person, surrounded by adipocytes that rupture Vessel injury (vasculitis, radiation) (FA bind Ca and form soaps) sickle cell disease, intraosseous pressure long-term CS use Creeping substitution: osteoclasts Venous HT resorb trabeculae, deposit new bone on Scaphoid bone non-resorbed trabeculae (doesnt help Digits (Dactylitis in with subchondral infarct too slow) sickle cell)

** Greenstick fracture plastic deformation. Forearm, fibula common Medullary: chronically asx Other associated causes: Trauma, except for large ones in Infection, Dysbarism, radiation, CT Gauchers, dysbarism, Causes 10% of disorders, pregnancy, Gauchers, hemoglobinopathies 500,000 joint Sickle cell/other anemias, alcohol, replacements chronic pancreatitis, tumors, Subchondral: Chronic pain annually! epiphyseal disorders (initially only with physical activity, then gets more Legg-Calve-Perthes is aseptic Most cases constant). Can collapse, idiopathic/after CS necrosis involving femoral head cause severe secondary administration ossification in kids pain in osteoarthritis kneeling, limp is seen Mostly in 3-10 yr old BOYS. Commonly leads to secondary OA.

Condition

Diagnose It + blood cultures, Have to biopsy/bone culture to id pathogen

Osteomyelitis

Clinical findings Fever, bone pain, elevated ESR Metaplastic bone present Starts in musculature of proximal extremities Radiograph: Soft tissue fullness radiodensities at the periphery (3 wks) filled in radiodensity Have to differentiate from extraskeletal osteosarcoma (in elderly, cells are malignant, tumor doesnt have zonation)

Pathophysiology Pyogenic: Bacterial infection of a bone, from hematogenous spread, extension from another site, or direct implantation o 90% due to Staph Aureus (receptors for collagen) o UG infection or IV drug user: E coli, Pseudomonas, Klebsiella o Neonates: Strep pyogenes, H flu o Sickle cell: Salmonella paratyphi o But 50% cant find org! o Pseudomonas often from puncture of foot through rubber footwear. Tuberculous form: hematogenous spread from lung (goes to vertebra Potts disease, less often hip/knee) 13% get this. Multifocal in immunocompromised. Lesion 3-6 cm across, well-delineated Soft/glistening center; firm/gritty periphery Early: cellular lesion with plum/long fibroblast-like cells (simulates nodular fasciitis) Morphologic zonation (within 3 weeks) merges with adjacent intermediate zone of osteoblasts, woven bone deposited. Cancellous bone appearance on the outside. Skeletal mm fibers/giant cells often trapped in the margins. Ossification of all: intertrabecular spaces are filled with bone marrow

Pathology

Neutrophils enzymatically destroy bone (dead bone = sequestra) necrosis in 48 hrs. Chronic disease: reactive bone formation in periosteum (involucrum) Kids: subperiosteal abscesses from spread in Haversion canals Draining tracts to skin surface (danger of squamous cell carcinoma developing at orifice of sinus tract)

Clinical Course Where (depends on where blood supply is): Before growth plates close: metaphysic/epiphysis After growth plates close: more widespread Brodie abscess: small, intraosseous involves cortex, walled off by reactive bone Sclerosing osteomyelitis of Garre in jaw, new bone formation

Genetics/Epi

Treatment Antibiotics and surgical drainage 5-25% wont resolve (can go chronic if dx delayed, extensive necrosis, short tx, poor debridement or immunocompromised)

Complications: pathologic fracture, secondary amyloidosis, endocarditis, sepsis, sarcoma Metaphysis is most common site (with hematogenous spread)

Myositis ossificans

Metaplastic bone grows out in the muscle

Depends on stage of development: Early Swollen/painful Later Circumscribed, firm Even later painless, hard, well-demarcated mass

Athletic adolescents, young adults follows trauma in >50% of cases

Take it out! Usually solves the problem.

calcaneal apophysitis Severs inflammation of the growth plate of the calcaneus

most frequent cause of heel pain in children 8-13 yrs (seen during periods of active bone growth), especially if moderately obese

Self-limiting will disappear after bone growth finalized and growth plate closes (age 15-16)

Boys 11-15 yrs of age Inflammation of proximal tibial apophysis at insertion of patellar tendon. OsgoodSchlatter Stress on patellar tendon with repeat quadriceps contraction can cause avulsion fractures and microtrauma/inflammation (causes lump on knees) Radiograph not needed to diagnose, but confirm it and rule out other causes of knee pain Usually resolves with skeletal maturity (when tibial tubercle fuses to the remainder of the tibia) Ice after exercise, NSAIDs Syndig-Larson-Johansen syndrome involves the upper part of the tendon, where it attaches to the patella! Knobby appearing knees No effect on bone growth

Condition Bone tumors (basic epi and characteristics only)

Diagnose It Location of tumor most key diagnostically

Pathophysiology Benign ones: - more common than malignant, younger people

Pathology Metastasis most common bone malignancy (mostly from breast CA)

Clinical Course Malignant ones: - tend to be letal, in elderly

Genetics/Epi

Treatment

Osteochondroma (exostosis) Giant Cell:

Female, 20-40 Cells look like osteoclasts Soap bubble, Spindle-shaped multinucleated cells Epiphysis (distal femur/prox tibia) Osteoid osteoma Male, 10-20 Cortex of proximal femur, Radiolucent focus (nidus) surrounded by sclerotic bone Enchondroma 20-50 Medullary, small tubular bones Hands/feet Multiple or solitary, Risk of chondrosarcoma Male, <25, Mushroom capped w/benign cartilage , Metaphysis (distal femur), Most common benign, rare to go malig

Osteoma Males, Face, Assoc w/Gardners polyposis Dont go malignant, Big deal if compress something or ugly.

Osteoblastoma Male, 10-20 Osteoid osteoma in the vertebrae Radiation bad malignant transformation!

Chondrosarcoma Male, 30-60 Pelvic bones, proximal femur Mushroom shape

Ewings sarcoma Male, <15 Pelvic girdle, diaphysis/metaphysic of prox femur/rib Small, round cell tumor Onion skin X-ray periosteal rxn. Possible fever/anemia

Osteosarcoma Male, 10-25 Metaphysis of distal femur/proximal tibia sunburst appearance (from calcified osteoid), Codmans triangle (tumor lifts periosteum), Metastasizes to lungs MOST COMMON PRIMARY BONE CA

Targets pelvis, skull (enlarged), femur Cause unknown (virus paramyxovirus?) Or abnormal osteoclasts (hyperresponsive to vit D, RANKL) Pagets Disease of the Bone (Osteitis Deformans) Overall, you gain bone mass, but its disordered in structure and structurally unsound. Risk of osteogenic sarcomas, risk of high-output HF (from AV connections in vascular bone) 1) Osteoclastic resorption of bone (shaggy-appearing lytic lesions) 2) Osteoblastic bone formation (d serum alkaline phosphatase, Normal Ca/PO4, thick/weak mosaic bone formed) mixed w/osteoclast activity 3) Osteosclerotic phase (quiescent) * Mosaic pattern of lamellar bone * Dx: Incidental radiographic NOT usually in ribs, fibula, small hand & feet bones Generally asx Pain: most common problem, in the affected bone. Microfractures/overgrowth (compressing nerve roots) Leontiasis ossea: craniofacial growth , difficult to hold head erect -> platybasia (flattened skull base) Bowing of femor/tibia causes secondary osteoarthritis Chalkstick-type fractures in long bones of lower extremities Compression fractures of spine Skin over pagetic bone is warm (hypervascularization) Non-malignant: Giant cell reparative granulomas, giant cell tumor, extraosseous masses of hematopoiesis My hat size d!

Elderly white men of Europe, Australia, US, 5-11% of population affected in countries where it exists Genetic link to 18q Note: Parathyroid adenoma or hyperparathyroidism would be different you get brown tumors, which are areas of d bone mass. Suppress sx w/ calcitonin/biphosphates

Condition Diagnose It Rheumatologic Disorders

Pathophysiology

Pathology

Clinical Course Lacrimal glands (keratoconjunctivitis), Minor salivary glands (sicca), Parotid gland (dry mouth, dental caries, parotidis), Pancreas (achlorhydia, abdominal pain)

Genetics/Epi

Treatment

Sjogrens

Shermers test: evaluate for dry eyes

Exocrinopathy problem in T-cell regulation, B cell expansion (polyclonal), inflammation in EXOCRINE glands

Lab: Slightly serum alkaline phosphatase Radiograph: asymmetric loss of joint space, Eburnation (thickened endplate resulting in osteophyte formation), subchondral cysts, intraarticular loose bodies Noninflammatory joint disease cracking/narrowing of cartilage leads to reaction in underlying bone Focal arthritis = 90%. Loading/focal transarticular stress is main cause of hip/knee OA. Generalized osteoarthritis = 10% (generally genetic association) Progressive degeneration of articular cartilage targets wt bearing joints.

Erosion/clefts seen in articular cartilage Reactive bone formation at joint margins (osteophytes) causes slightly alkaline phosphatase Subchondral cysts Bone eventually rubs on bone (producing dense, sclerotic bone) NO joint ankylosis Crepetis grinding in joints Pain w/passive motion (secondary synovitis)

Hand involvement! DIP enlargement Heberdens nodes PIP enlargement Bouchards nodes

Most common disabling joint disease! More in women, universal after age 65 Secondary causes: Obesity, trauma (valgus/varus stress of knee, meniscal or ACL injury), ochronosis (alkaptonuria AR disease w/deficient homogentisic acid Oxidase, accumulation of homogentisic acid which deposits in IV discs urine will turn black when oxidized)

General approach: o Joint protection, stabilization, o Analgesia (NSAIDS, tramadol, codeine), o Joint-specific (injections corticosteroids, hyaluronic acid analogues). Surgery not that great. In development: oral immunomodulators, maybe antimetaloproteases

Osteoarthritis *Cartilage*

Vertebral findings: Degenerative disease w/ compressive neuropathies

Synovial inflammatory disease: proliferation, erosion into marginal bone Lab: RF, Rheumatoid arthritis *Synovitis* Research: CCP ab for diagnostic? Rice bodies floating fibrogen in synovium Cartilage: 70% water. Chondrocytes are 10% of tissue volume (manufactures, secretes, maintains matrix components collagen, hyaluronic acid, proteoglycan). Ag driving rheumatoid arthritis is unknown perhaps IgG Fc, CCP, Type II collagen. Initiating ag might differ from perpetuating ags.

Complications: Secondary Sjogrens; rheumatoid nodules, vasculitis, entrapment neuropathy (carpal tunnel), pulmonary fibrosis, pleuro-pericarditis, membranous glomerulonephritis. 3-4X rr of lymphoma (also risk of lung cancer maybe due to immunosuppressive?), osteoporosis (generalized inflammation causes IL-1 related demineralization, and chronic disease-related malnutrition), atherosclerosis (3 rr CV mortality due to acceleration!), ACD

Swelling leading to pannus. Periarticular osteopenia. Marginal erosion, joint space narrowing, malalignment.

Most develop structural damage early on (as early as 4 months to 5 years into disease) HLA DR4

Usually doesnt affect DIPs Joint morphology similar to adults targets knee/wrist/elbows/ankles. Warm, swollen, often symmetrical involvement. Complications pericarditis, myocarditis, pulmonary fibrosis, glomerulonephritis, uveitis, growth retardation Begins before age 16 and must be present for at least 6 weeks to make diagnosis 2:1 female (except 1:1 systemic) ~40,000 in US 1/3 -1/2 have active disease after 10 yrs

Education, OT, PT, NSAIDs, Prednisone, Synthetic DMARDs (Methotrexate, sulfasalazine, leflunomide, hydroxychloroquine), Biologic DMARDs tx (against TNF, IL-1, Tcell, Bcell, IL-6) Now largely based on physician preference

Juvenile RA

Usually rheumatoid nodules and rheumatoid factor absent. Antinuclear ab seropositivity common

Genetic association w/HLA (DRB1), infections, abnormal immunoregulation (CD4+ Tcells in joints)

Oligoarticular (<5 joints) Polyarticular (>=5 joints) Systemic form more frequently systemic than the adult form. Assoc w/ high fever, rash, hepatosplenomegaly, serositis.

Condition Diagnose It Rheumatologic Disorders

Pathophysiology

Pathology

Clinical Course 4 Stages: 1) Asx hyperuricemia (puberty in males, postmenopause in females) 2) Recurrent acute arthritis: Podagra: recurrent acute arthritis in big toe 50% have as 1st manifestation Fever, pain, neutrophilic leukocytosis MSU phagocytosed by PMNs in synovial fluid 3) Intercritical Gout 4) Chronic gout Tophi: deposits of MSU in soft tissue around joints. Granulomatous rxn w/multinucleated giant cells destroy subadjacent bone (causes erosive arthritis). White deposits on helix of ear

Genetics/Epi Often men >30 Assoc w/urate nephropathy, renal stones, HT, CAD, Lead poisoning (interstitial nephritis interferes w/uric acid excretion) 10% of US has hyperuricemia, but <0.5% develop gout Risk of hyperuricemia becoming gout: Age/duration, Genetic predisp (multifactorial inheritance factors), Alcohol use, Obesity, Drugs (thiazides), Lead

Treatment Really important to tx early impairs quality of life, and a lot of aspects of the disease due to duration/severity of hyperuricemia. Hyperuricemia: not tx if asx Acute arthritis: NSAIDs, colchicine, intra-articular corticosteroid injection, oral corticosteroids Recurrent arthritis or tophaceous gout: o Allopurinol: inhibits Xanthine Oxidase to stop uric acid production o Febuxostat (hepatically excreted, can be used in pts with renal failure) Want to bring uric acid level <6.

Gout *Crystal*

Lab: Hyperuricemia, joint aspiration (arthrocentesis) confirmatory MSU crystals w/NEGATIVE biorefringence crystals are YELLOW when parallel to slow ray, blue when no longer parallel.

Primary gout (90%): underexcretion of uric acid in kidneys (lead poisoning, alcoholism are secondary causes), enzyme deficiencies are rare (HGPRT) Secondary gout (10%): Overproduction of uric acid ( cell turnover, chronic renal disease, diuretics). Estrogen s tubular excretion of uric acid.

Urates in joint fluid supersaturated, unknown event initiates release of crystals into synovial fluid. Leukocyte chemotaxis, complement, LTB4, Activation of Hageman factor

20% end up dying of renal failure

Pseudogout (CPPD or chondrocalcinosis)

Lab: Calcium pyrophosphate crystals phagocytosed by PMN show + biorefringence crystals BLUE when parallel to slow ray (white friable deposits, oval-blue staining, geometric shapes)

Degenerative joint disease, usually involves knee. Crystals produce linear deposits in articular cartilage elicit IL8 production (inflammatory rxn)

Frequently asx, but can produce acute to chronic arthritis that mimics other things (RA, osteoarthritis) most commonly affects knees/wrists 50% have significant joint damage

Usually >age 50 (more w/ age) 30-60% of those >85 have it

Hereditary form early development in life, get severe OA AD (ANKH mutation that encodes transmembrane inorg pyrophosphate transport channel) Tx supportive (no known treatment to crystal formation)

Condition

Diagnose It

Pathophysiology Immune-mediated manifestations, may be triggered by T-cell response to unknown ags. Inflammatory peripheral/axial arthritis w/inflammation of tendinous attachment See below

Pathology Included Syndromes are PEAR: Psoriatic arthritis Enteropathic arthritis Ankylosing Spondylitis Reiters Syndrome Undifferentiated (parts of all) also exists Sausage-shaped DIP joints (finger or toe Dactylitis 50%)

Spondyloarthropathies: *Enteritis*

Seronegative (RF neg) Sacroiliitis w/ or w/out peripheral arthritis

Clinical Course Happens with IBD (Crohns, ulcerative colitis) in addition to below. Generally due to molecular mimicry Oligoarthritis (a few joints causing arthritis usually knee/ankle)

Genetics/Epi Initiated by environmental factors (prior infections/exposures) HLA-B27 link Male dominant

Treatment Need to tx underlying disease. Exercise, adaptive footware. NSAIDs, Intra-articular steroids, DMARDs (Disease-modifying antirheumatic drugs sulfalazine, methotrexate, anti-TNFa)

Radiology: Erosive joint disease pencil in cup deformity Psoriatic arthritis

Similar histologically to RA (but less severe, frequent remissions, joint destruction happens less)

Extensive nail pitting Joint sx have slow onset (acute in 1/3 of pts) Sacroiliac/spinal involvement (20-40%) - Sacroiliitis

Pt age 30-50 10% of psoriasis pts have this

Ankylosing Spondylitis (rheumatoid spondylitis/Mar ie-Strumpell disease)

Low back pain Bilateral sacroiliitis w/morning stiffness Eventually involves vertebral column (bamboo spine -> leads to forward curvature) Radiology: Achilles tendon periostitis is confirmatory sign.

Chronic inflammation of axial joints (especially sacroiliac, apophysial) Chronic synovitis w/ destruction of articular cartilage, bony ankylosis. Inflammation of tendinoligamentous insertion sites (they ossify -> produce bony outgrowths) Cant see, cant pee, cant bend the knee Urethritis, Arthritis/Achilles tendon periostitis, Noninfectious conjunctivitis but not all have all 3 Extraarticular involvement: inflammatory balanitis, conjunctivitis, cardiac conduction abnormalities, aortic regurg. Waxing/waning arthritis, fasciitis, tendinitis, lumbosacral back pain Seeding during Bacteremia or neonates have spread from epiphyseal osteomyelitis Pasteurella multocida septic arthritis/tendinitis due to cat bite. May or may not have systemic symptoms. Synoviocyte hyperplasia, fibrin deposition, mononuc cell infiltrates, onionskin thickening of aa walls 5ths disease: parvovirus direct infection with secondary immune reaction.

1/3 have peripheral joint involvement Complications: spine fracture, uveitis (blurry vision), aortitis (w/aortic regurg), amyloidosis

20-30 yr old Men 2-3X > women 90% HLA-B27 +

Reactive Arthritis (Reiter syndrome, enteritisassociated arthritis)

Noninfectious arthritis of appendicular skeleton within 1 month of primary infection localized elsewhere in body. Perhaps autoimmune reaction initiated by prior infection. Follows infection: Chlamydia trachomatis (#1) or GI infection (Shigella, Salmonella, Yersinia, Campylobacter all have LPS)

Clinical Progression: Joint stiffness/low back pain early on mostly ankles, knees, feet (asymmetric pattern) Synovitis of digital tendon sheath -> sausage finger/toe Ossification of tendoligamentous insertions -> calcaneal spurs/bony outgrowths Sudden development of acutely painful/hot/swollen joint with restricted range of motion. Systemic = fever, leukocytosis, elevated sed rate Insidious onset, gradual progressive pain. Mostly in large joints/shoulders/elbows/ankle s (attacks last weeks-months) Observe characteristic slapped cheek rash (not in adults, kids only). No tx needed, spontaneously remits.

Really chronic - can have spine involvement indistinguishable from Ankylosing spondylitis

Enthesitis (inflammation in cartilaginous transition between tendon and bone)

80% HLA-B27 +

Suppurative arthritis

Most common causes = H flu (<2 yrs), S aureus (older children/adults), gonococcus (late adolescence/young adulthood more in women), Salmonella (sickle cell pts) Mycobacterium tb hematogenous spread from visceral infection site Borrelia burgdorferi skin infection disseminates, suspected OspA cross reaction with proteins in joints Parvovirus B19, rubella, Hep C may be due to direct infection or autoimmune reaction?

Predisposed to it if immune deficiencies, illness, joint trauma, chronic arthritis, IV drug abuse All ages, especially adults 60-80% of untx pts get joint sx

TB arthritis Lyme arthritis Silver stain shows organisms near blood vessels in 25%. Question if this is involved in development of RA

Viral arthritis

Condition

Diagnose It Pain all over Neck/shoulder/hips especially a problem Pain impairs sleep Migraine headaches Hyperemesis in pregancy

Pathophysiology Symmetric pain, above and below the waist. 11 of 18 tender points tender to touch when examined by physician (occiput, low cervical, trapezius, supraspinatus, second rib, lateral epicondyle, gluteal, greater trochanter, knee) but no limit to where you will feel pain

Pathology

Clinical Course

Fibromyalgia *Amplification Attachment*

Genetics/Epi Some question if this is causative or secondary to chronic

Treatment Relaxation techniques, improve sleep disorder, stretching postural muscles, aerobic conditioning NSAIDs, Tramadol, Tricyclic antidepressants, SSRI, Neuronitin, Lyrica

Likely a thalamic problem of pain amplification. May be accompanied by depression, migraines, IBS

disease Heterogeneous disease: Malar butterfly rash, mucosal ulceration, alopecia, inflammatory arthritis, serositis (pleural effusion, pericarditis, ascites), Immune based cytopenias, glomerulonephritis, cerebritis (seizure/neuropsychiatric sx), Predisposed: 90% female, childbearing age, EBV, exposure to UV light, 8 susceptible loci, Sunscreens, Topical/oral steroids, hydroxychloroquine (reduce skin sensitivity), Azathiaprine, mycophenolate, cyclophosphamide Experimental: Anti-CTLA4, Anti CD20, Anti BlyS, Anti BAFF, Bcell tolerogan

SLE *Deposition

Serologic abnormalities (autoantibodies, compliment consumption, antiphospholipid abs)

C1q/C2/C4 deficiencies, loss of immune tolerance to nuclear autoags, B-cell hyperactivity, T-cell dysregulation

Systemic Vasculitis *Infarction*

Fever, Rash (skin infarction), Inflammatory arthritis, Mononeuritis multiplex, multiple cortical infarctions, cellular casts Labs: Anticentromere ab in 90%, Serum ANA + in 70-90%, Antitopoisomerase ab + in 15-40% Crest Syndrome: Calcification, centromere ab Raynauds phenomenon

Ex: o Temporal arteritis, o Takayasus/Giant cell (large arteries) o Classic polyarteritis nodosa/Kawasaki (medium arteries)

o Wegeners granulomatosis, microscopic polyangiitis/ChurgStrauss syndrome (Small arteries) o Cryoglobulinemia/cutaneous leukocytoclastic vasculitisHenochSchonlein purpura (Arterioles)

Fever, Rash

Sclerodactyly (tapered, claw-like) T-cell mediated release of cytokines causes excessive production of collagen that primarily targets the skin, GI tract, lungs, kidneys Small-vessel endothelial cell damage produces blood vessel fibrosis and ischemic injury Limited: only distal to elbows/knees Generalized: More serious, whole body Morphea is a localized form of scleroderma

Scleroderma *Collagen*

Skin: atrophy, tissue swelling starts in fingers and extends proximally. Looks like parchment. Extensive dystrophic calcification in subcutaneous tissue. Tightened facial features (d dermis, d epidermis), ulceration GI: Dysphagia (Esophageal dysmotility no peristalsis in lower 2/3 of esophagus because smooth muscle replaced by collagen). Small bowel has loss of villi (malabsorption) and wide mouthed diverticuli (bacterial overgrowth)

Respiratory: Interstitial pulmonary fibrosis, Pulmonary HT Renal: Vasculitis of arterioles and glomeruli infarctions, Accelerated malignant HT Mostly women of childbearing age

No overall disease modifying drug yet. Better agents needed for bowel dysmotility Renal crisis ACE inhibitors Interstitial lung disease: Cyclophosphamide, Cellcept, biologics (remicade, Rituxan) Pulmonary HT (short term benefit): Coumadin, Bosantin, Revatio, Ventavis, Remodulin, flolan Digital ulcers: Ca channel blockers, Viagra, Stellate ganglion block and palmar sympathectomy

Telangiectasis

Esophageal dysmotility fracture through the epiphyseal growth plate of the proximal femur

SCFE (slipped cap femoral epiphysis)

Klein's Line normally disects part of the femoral head, in SCFE the line no longer disects the head

Insidious onset of hip or thigh pain, painful limp, d motion (IR), Signs: painless limp, knee pain, d IR of hip

Males 12-15 yrs: blacks, endocrinopathies, thyroid Girls 10-13 yrs Bilateral in 25%

pin in situ with cannulated screws do not reduce for fear of disruption of blood supply causing avascular necrosis

Condition

Diagnose It

Pathophysiology

Pathology

Clinical Course

Genetics/Epi

Treatment observation, brace (TLSO, milwaukee), PT (electric muscle stimulation), osteopathic, chiropractic, surgery

Scoliosis

Cobb angle: standard method for assessing the curve quantitatively

complex lateral and rotational deformities of the spine

Congenital Hip Dislocation

Screening by PE should begin at birth; a child who has not begun to walk by 18 mths should be suspected Sometimes not noticed until a limp or other abnormal gait is noticed when the child starts walking

The buttocks and perineum may be unusually broad and adductor folds may be present on the medial aspects of the thighs.

PE shows inability to aBduct the thighs to 90 degrees in flexion Ortolani jerk sign is pathogmonic for subluxation

In childhood& adolescence, signs include a female contour to the pelvis(both sexes have a male

Joint Replacement Support injured body part Encompass: o Sprain (ligament injury) o Strain (other soft tissue injury) o Contusion (bruise) o Fracture (hard tissues bone or cartilage) o Stress reactions (ask body to do something youre not capable of doing stress fracture, shin splints medial tibial stress syndrome) Splint, cast duration depends on extent of injury Bony injury 4-6 weeks (older pt); 2-4 weeks (younger pt) Most common musculoskeletal complaints in younger pts Soft tissue may put walking boot on pt for much longer (can take longer to heal) Medications: NSAIDs (relieve inflammation and pain), Analgesics (pt more comfortable, improve their functionality/mobility) Physical therapy the earlier pt up and moving, the faster their recovery NSAIDs: relieve underlying inflammation, resulting in sx relief. Do not correct underlying problem Immune modulators may provide longer sx control, more expensive Physical therapy Hereditary/ other etiologies History: suggested by progressive muscle weakness. Positive family hx suggests genetic transmission Physical exam: Muscle weakness (note symmetry, proximal vs distal Depends on disease process. Physical therapy often an important component. Antibiotics: Start w/broad spectrum, then change to more specific antibiotic when culture returns. Bone infections may require extended course. Surgery: Incision and drainage of abscess (have to no good blood supply), Debridement of soft tissue infection, debridement of infected bone follow with course of antibiotics

Sprains, Other activityrelated disorders Overuse and injury:

History can often determine inciting event acute injury, changes in training pattern or schedule Physical Exam can find soft tissue swelling, bruising/discoloration, ligament laxity, muscle defects

Inflammatory etiologies:

Labs: ESR: non-specific elevation indicates an inflammatory process ANA- Non-specific (high cross reactivity). Abnormal test must be correlated w/ elevated ESR Follow screens w/specific tests (like anti-dsDNA)

History: Usually insidious onset, no inciting incident (activity may make better or worse). But really, pt will improve with exercise. Pt often report use of OTCs, alternative meds

Exam: Inflammatory signs: soft tissue swelling, erythema, inflammatory nodules

Ex: Autoimmune and collagen vascular arthritis, Osteoarthritis

Lab: muscle biopsy, genetic testing

Infectious etiologies

Labs: CBC (nonspecific), C-reactive protein (non-specific), culture Radiologic eval: CT/MR may show soft tissue or bony infection. Bone scan localizes at inflamed/remodeling bone. Tagged WBC scan localizes at site of infection.

History: Insidious or acute onset; fever/malaise common Cellulitis, soft tissue abscess, osteomyelitis

Exam: Local erythema, tender/fluctuant mass, bony tenderness, open weeping sore (osteomyelitis)

Condition

Non-Operative Orthopedics Lecture (Primary Care Sports Med)

Osteopathic Medicine Overview

Non-

Diagnose It Pathophysiology Pathology Clinical Course Genetics/Epi Treatment Primary Medical Areas of Concern: Respiratory Screening o CV, Respiratory, Illness/Fatigue, Neurological, GI, UG, Menstrual Irregularities, Eating Disorders, o Asthma and exercise-induced asthma, pneumothorax, infectious process Psychological o Hx: wheezing, SOB, chest tightness, fatigue/feeling out of shape, chest pain, allergy Annual Screening Exam: Ht, wt, BP, pulse, injury review/rehab review o Exercise-induced asthma: flares with exercise, heightened environmental factors Cardiac screening: Looking for prevention of sudden death ask about syncope, chest pain/palpitations (allergies, smoke, cold weather, low humidity) during or after exercise. Questions to ask: Sudden death in family member <50 yo, sudden family hx of heart o Physical: lung auscultation, allergy sx, chronic sinusitis (hear after exercise, compare it disease, syncope/lightheaded w/exercise, Dyspnea/easy fatigue w/exercise, palpitations/chest pain w/exercise, to how they feel) Previously detected murmur/elevated bp o Tx: Allergy control, short-acting B-agonists (albuterol), Long-acting B-agonists o Recent illness, medications/supplements, alcohol/substance abuse, direct blow vs non-contact, PPQRST, (severent), anti-inflammatory agents (cromolyn), Steroid preps (advair) other pertinent hx o Pneumothorax: acute onset of chest pain w/dyspnea and tachycardia, Hx of a collision o Physical exam: Vitals (essential Heart rate for rhythm and rate, pulses radial/carotid/femoral/ or this is spontaneous. Physical: Auscucltation (decreased breath, sounds on dorsalis pedis, BP, resp rate, temp) affected side), tachycardia, anxious, dyspnea, mediastinal shift o Auscultation: S1/S2, murmurs, S3 can be normoal in young children and some athletes (question HF o Infections: fever, malaise/fatigue, N/V, diarrhea, mm aches, lightheadedness, dizziness if >40 yo), S4 (normal in athletes). Grade 3 murmurs or louder need greater work-up (esp if increase o When to refer? Temp >101F, Chest pain/palpitations, dyspnea, head injury, w/valsalva - cardiomyopathy or diastolic murmur-mitral stenosis, aortic regurg) collapse/syncope, skin lesions, seizure hx, persistent weakness/paresthesias, severe o Sudden Death: <35 yo due to hypertrophic cardiomyopathy, coronary a anomalies, arrhythmias, Long allergies, loss of a paired organ, unexplained wt loss, menstrual changes QT, Marfans, Prevalence 1:100,000 to 1:300,000 (School-aged), 1:15,000 (Joggers), 1:50,000 o Return to play is often gray: rest, fluids, sx control (Marathoners) Neurological o Syncope: Vasovagal, cardiogenic, neurogenic o Concussion (simple vs complex), have to do hx, PE to suggest that they need to stay o Chest Pain/Palpitations: Arrythmias, Repiratory (asthma/bronchitis/pneumothorax), musculoskeletal, from play longer. To return to play following concussion, want to ensure sx free at psychogenic rest, with minimal exertion, with light cardio/lifting, with gility drills/heard non-contact o Marfans: Changes in aorta (can have rupture), lots of tall/lean athletes, sunken in chest, long fingers, workout progress back to practice for tolerance EKG, heart work-up really important in these pts. Osteopathic treatments: DO=Doctor of Osteopathic Medicine o Muscle energy: direct technique pts activate mm opposite the area of restriction which causes In other countries, osteopathy is often a form of complementary medicine emphasizing holistic reciprocal inhibition and relaxation of the mm that are tight, can be used anywhere in body approach to health care using manual medicine (bachelor degree equivalents these arent licensed o Myofascial release: indirect soft tissue technique used to stretch and relax muscular and fascial physicians) restrictions, very gentle Founder: Andrew Taylor Still MD (1917) o Counterstrain indirect, focuses on identifying tender points. Places pt in position of ease 4 principles: 1) The body is a unit. 2) The body possesses self-regulatory mechanisms. 3) Structure around the tender pt to reduce activity efferent nerves thereby decreasing pain. Goal is to hold and function are reciprocally interrelated. 4) Rational therapy is based on understanding of 1 st 3 for 90 seconds and reduce pain by 70%, pt must be completely relaxed throughout tx principles. o Popping and Cracking high velocity low amplitude thrust. Mobilization with impulse. Direct Key terms: moves a dysfunctional segment through its restrictive barrier nd resets itself. To restore o OPP: Osteopathic Principles and Practice physiologic motion. Precise positioning and set-up is key. (Dont attempt this at home). o OMT: Osteopathic Mnipulative Tx Cautions: hypermobile joints, osteoporosis, acute fractures, radicular sx, contractures, pts o OMM: Osteopathic Manipulative Medicine w/rheumatoid arthritis. Risks: Permanent neurological damage, vertebral basilr thrombosis, Uses of OMT: Infections, CHF, lymphedema, asthma/COPD exacerbations, chronic back/neck pain, carotid a dissection, death or quadriplegia if disrupt transverse ligment of atlas HA, Acute musculoskeletal injuries, post-operative ileus/constipation/diarrhea, arthritis (joint o Lymphatic Pump: Maintains fluid balance purification and cleansing of tissues, defense problems), Pregnancy issues, Newborn issues, Post CABG/CPR against toxins/bacteriaviruses, nutrition, sympathetic nervous system constricts lymphatic Somatic Dysfunction: An impairment or altered function among related components of the body, vessels. OMT cn lymphatic fluid circulation. Lymphatic techniques include rib raising, including skeletal, arthroidal, myofascial structures in addition to related vascular, lymphatic, and thoracic inlet, doming diaphragm, pedal pump, liver/splenic pump, Galbraith technique. CI if neural elements Crcinoma, acute fracture in area of tx, abscess/localized infection, bacterial infection TART: Tissue texture changes (edema, warmth, redness, hypertrophy, atrophy, rigidity, bogginess, w/temp>102 stringiness), Assymetry, Restriction, Tenderness o Articulatory Techniques: Gentle, direct tx range of motion in restricted joint. Spencer Barriers to motion: technique of GH joint (OA, shoulder strain, frozen shoulder), rib raising (s chest wall motion, o Anatomic (the limit of passive motion which if breached causes damage) improves lymphatic return, normalizes sympathetic tone in pneumonia, COPD/asthma exac). CI o Physiologic (the limit of active motion) if acute fractures, acutely inflamed joints (caution in cervical area vertebral aa compression) o Pathologic/Restrictive: functional limit within the anatomic motion which s the physiologic o Craniosacral primary respiratory mechanism. Inherent motility of brain/spinal cord, range fluctuation of CSF, movement of intraspinal and intracranial membranes, articular mobility of Acute Somatic Dysfunction: Vasocilation, Inflammation, Warm moist skin, d mm tone, edema, cranial bones, involuntary mobility of the sacrum between the ilia. Firm attachments of dura to bogginess, severe/cutting/sharp pain foramen magnum, C2, C3, S2. Membranes that surround, support CNS are dura, arachnoid, and Chronic Somatic Function: Cool pale skin, d mm tone, doughy tissue texture, stringiness, fibrotic pia mater. There is a subtle, pulse-wave like motion of the brain/spinal cord. There are changes, dull/achy/crawling/itching/burning/gnawing pain measurable, inherent movements in these structures with respiration. Goals: balance motion Reflexes: Viscerosomatic-viscerl input that is referred to a corresponding segmental somatic structure. SBS, reduce venous congestion, enhance rate and amplitude of CRI, mobilize and correct Somatovisceral-somatic stimuli produce responses in segmentally related visceral structures membranous articular restrictions (contraindications intracranial hemorrhage or elevated ICP, Direct techniques: Move tissues/joint into the barrier, or into the restriction uses force to create skull trauma, seizures), Complications changes in HR/BP/RR, GI irritability, Tinnitis, motion into and beyond the restrictive barrier Dizziness, HA Indirect techniques: Move tissue/joint to a position of ease, away from the barrier or restriction Evidence-based medicine: Low back pain, carpal tunnel syndrome, otitis media, post-op pts, COPD allows the bodys inherent neurologic or intrinsic forces to free up the restriction excerbations Type Example Use Manual medicine (see DO lecture)

pharmologic Mnagement of Musculoskelet al problems

Herbal/nutritional supplements o Early research lacking (lots of placebo effect, many preps lack purity). Most newer research reveals minimal utility o Glucosamine/chondroitin: Building blocks of CT Glucosamine is an amino sugar, distributed in cartilate/other CT, Chondroitin is a complex carb, auds in water retention of cartilage. Both are normally made in the body. not sure how it works since these are both denatured in stomach acid. Use in OA o DMSO (Dimethyl sulfoxide): industrial solvent. Can be used to aid in transport of other substances into soft tissue has innate antioxidant and anti-inflammatory properties. Studies show pain relief in OA. FEDA approved only for tx of interstitial cystitis. Know i ts working because you get a garlic taste in your mouth. Acupuncture o Balance of yin (cold/slow/passive) and yang (hot/excited/active). Health is a balance, disease is imbalance. Imbalance leads to blockage of qi (vital energy) along pathways (meridians). Acupuncture points are connections between meridians. o Uses: pain management interrupt transmission of painful impulses (decrease pain, increase functionality), treat disease (by restoring balance to allow body to heal) o Current research: does it work, how? What are the complications local infections, puncture of organ/blood vessel. Physical Therapy modalities o Comprehensive tx plan therapeutic exercise, manual techniques, modalities. Important component of tx for musculoskeletal problems. Adjunct tx for cardiac/pulmonary/developmental disorders Therapeutic exercise: improves strength, mobility, function. Decreases pain/swelling, home-based (brief instruction in office, effective after ACL reconstruction), supervised (superior to home-based for low back injury or OA, may involve home component) Bracing and orthotics Plain X-ray: Strengths: Bony injury, Availability, fast, inexpensive, if + imaging workup often done. Good for acute fracture, arthritides, bone lesions Limitations: Sensitivity, Cant see soft tissues, early osseous pathology (stress injuries, mets/myeloma) 1st line screen Definitive arthritis Indicative ex w/ACL CT: Strengths: fracture detection, fracture morphology, fracture healing, osseous fusion, added specificity to MR, multiplanar and 3D reformats. Less hardware artifacts (multidetector), bone lesions. Good for bony injury, some utility for soft tissue. Limitations: More expensive, high radiation exposure, soft tissue, bone marrow pathology

Closed kinetic chin (both ends are attached) Concentric (mm contracting in an equal fashion all the time) Core stability Eccentric (mm relaxes through the exercise) Isometric (mm doesnt shorten at all) Isotonic Open kinetic chain

Leg press, squat Flexor phase of biceps curl

Shoulder/knee rehab Increase mm mass and strength Relief of low back pain Sport-specific strengthening Toning conditioning Functional improvement in ADL

Abdominal crunch Extension phase of biceps curl Holding a wt Free-wt lifting Quad extension

MR:. Strengths: Best for soft tissue, Bone ok, multiplanar, no radiation Limitations: Expensive, less available, weight limitations, claustrophobia Contraindications (implants, pacemakers), time

Evaluation of Injury (different radiological tests, etc)

Ultrasound: o High frequency sound waves warm surrounding soft tissue o Uses tendon injuries, mm strain/spasm o Cautions with malignant tumors, bone, pacemakers, epiphyseal plates o Phonophoresis: use ultrasound to deliver meds to soft tissue (cs, NSAID, DMSO). Minimal penetration of meds, possible systemic effects of meds o Iontophoresis: use electrical current to deliver meds to soft tissue use for CS, acetic acid (in myositis ossificns). Avoid near metallic implants, wires, or staples o Electrical stimulation: electrical stimulation generates muscle contraction use for mm spasm or contusion. Electrical current alters sensory input (TENS transcutaneous electrical nerve stimulation) use for neuropathic pain syndromes). Avoid around pacemakers o Low level laser tx: alters cellular oxidative metabolism. Uses: minor musculoskeletal pain, OA, RA, carpal tunnel. Avoid in pregnant, malignancy Arthrography: put fluoroscopic Ultrasound: Bone scan: Indications: Osseous metastases, guidance or ultrasound guidance to fractures (traumatic and stress) put contrast into a joint (gives you Strengths: soft tissues better look at joint in question) (tendon, ligament, muscle, Strengths: can help diagnose occult fracture nerve), no radiation, dynamic, bone remodeling process takes up Strengths: powerful when cheaper than MR pyrophosphates and will be detectable in combined w/MRI/CT. Labrum areas of remodeling bone. Total body screen, (shoulder and hip TFC, SL, and LT Limitations: Operator low cost (relative to MR), sensitive, ligaments wrist rotator cuff), dependent, bones (?) and deep physiologic (perfusion, osteoblastic activity) chondralosteochondral lesions, post tissues (if large pt size), operative meniscus; physician time, referring Limitations: Lack of specificity (stress shoulder/hipwrist/elbow/ankle/knee clinician consultation reaction, fracture, arthritis, tumor, infection); elderly (>72 hrs). Expensive, less available Limitations: invasive, indirect An excellent modality in (pyrophosphate degrades over time) information if not combined w/ skilled hands MRI or CT

Condition Diagnose It Orthopedics Lectures: Cervical

Pathophysiology

Pathology

Clinical Course

Genetics/Epi

Treatment

HNP: Herniated disc

Causes nerve compression or irritation Commonly insidious, but can be from trauma/injury

Depends on level involved o C4-5 (C5 nr) = deltoid weakness, not much numbness, shoulder pain o C5-6 (C6 nr) = biceps, wrist extension, NT along radial aspect o C6-7 (C7 nr) = triceps, finger ext, nt posterior to middle finger o C7-T1 (C8 nr) = grip strength, NT to little finger Fracture: Traumatic (stable or unstable), Flexion type = 45-75%, extension type = 20-35%, Compression = 12%

Pain, numbness/tingling, weakness, limited motion, radicular

Age 30-50

Tx: rest, cervical collar, traction/pt, NSAIDs/Steroids, epidural injections or Surgery (discectomy, w/ or w/out fusion).

DJD (Degenerative Joint Disease) Shoulder

Stenosis: anything that causes narrowing of the canal or foramen (arthritis, HNP, dislocationsubluxation, infection)

Arthritis: Insidious, accident/trauma, disease process. See pain, restricted motion, radicular sx, numbness/tingling, often times insidious onset, pt complains they slept wrong, neck pain

Other: Cervical radiculopathy, Brachial plexopathy can be due to infection

Stinger whole hand/arm goes numb due to hard hit on the side tends to be a temporary thing Tx: conservative rest, NSAIDs, subacromial injection, PT. Then surgical subacromial decompression arthroscopic or open w/or w/out rotator cuff repair, correct instability

Impingement

narrowing of the subacromial space (<7 mm by MRI) Hawkins test: Test for subacromial impingement or rotator cuff tendonitis. Can indicate pathology of biceps brachii or rotator cuff. Grasp elbow and wrist, flex to 90 degrees. Humerus passively internally rotated.

acromial spur, clavicular spur, CA ligament thickening or calcification, hypertrophy of rotator cuff, loose body, fracture (greater tuberosity), OS acromiale, secondary to instability. Neers test: Stabilize posterior shoulder, grab elbow and forarm pronated passively move arm up. Can indicate impingement of the rotator cuff tendons under the coracoacromial arch

Causes rotator cuff irritation, tear; pain/weakness

Diagnose impingement

Empty can test: The patient attempts to elevate the arms against resistance while the elbows are extended, the arms are abducted and the thumbs are pointing downward. indicates tendinitis, tear of tendon, supraspinatous w/impingement.

Drop arm test: raise arm as high as possible, slowly lower to 90 degrees. If rotator cuff tear or supraspinatous disfunction, their arm will drop to the side. The patient may be able to lower the arm slowly to 90 degrees (because this is a function mostly of the deltoid muscle) but will be unable to continue the maneuver as far as the waist.

+ test if pain with motion. + is with pain of motion.

Pain or weakness is +,

Rotator cuff tear

Supraspinatus (helps deltoid abduct arm) suprascapular n (C5/6) Infraspinatus (laterally rotates arm) - suprascapular n (C5/6) Teres minor (adducts and laterally rotates arm) axillary n (C5/6) Subscapularis (medially rotates and adducts arm) subscapular/thoracodorsal nn

Arthritis

Glenohumeral joint from insidious, traumatic, other Acrohumeral joint from traumatic, osteolysis, insidious

often need to do injection to help pain/inflammation

Condition

Diagnose It

Pathophysiology Rarely in superior direction because rotator cuff would have to be torn first and so would coracoacromial arch (95% occur anterior and inferior where there is least ligamentous reinformcement it may look completely anterior because subscapularis pulls it medially, but it is also inferior this is important to remember if you are setting it back into place) Around the glenoid, usually s stability of ball in socket Traumatic (throwers, car accident, tennis players)

Pathology Frequently associated with axillary nerve injury (wraps around humerus laterally around 1.5-2 inches inferior to acromion). Check sensory component by checking pinprick sensation over lateral deltoid area Person will have arm down, be kind of holding it up to prevent movement Tear can lead to other problems

Clinical Course

Genetics/Epi

Treatment

Dislocation

Labral tear/Instability Biceps tear/instability

Can put anchor in bone to help stabilize it.

SLAP tear

Susceptible to injury because it is an area of relatively poor vascularity. Other parts of the labrum often heal more easily because the blood supply delivers a healing capacity to the area of the tear.

catching sensation, pain with shoulder movements, most often overhead activities such as throwing

Tenosynovitis Fracture

Superior labrum tear anterior to posterior inflammation in the tendon Proximal humerus more common in older pts, clavicle, glenoid

tend to fix laproscopically Can become calcified

pain, weakness, circulatory changes

Thoracic outlet syndrome

compression of nerves/vasculature in the neck

RSD (reflect sympathetic dystrophy Elbow Arthritis Instability ulnar humeral, radial head

pain way out of proportion with what you would expect laborers traumatic or insidious fracture is monteggia, Median n: Anterior interosseous nerve (largest branch, passes between 2 heads of pronator teres impairs pinch ability) or Carpal tunnel syndrome (most common thumb, index, middle finger most discomfort at night) If large part broken, can fix w/screws Ulnar: Ulnar tunnel syndrome (cubital tunnel, between flexor carpi ulnaris mm heads d stretch w/elbow flexion). Snapping Ulnar Nerve (subluxation): 16% of all individuals it moves

Nerve Compression:

Radial n: Posterior interosseous n (between 2 heads of supinator functional involvement only) or Radial tunnel syndrome

Condition Hand/Wrist Ganglion

Diagnose It

Pathophysiology Tendon related (filled with synovial fluid).

Pathology

Clinical Course

Genetics/Epi

Treatment Treat by aspiration (50% recurrence) or surgical excision (510% recurrence)

mostly in the wrist (90%)

Carpal tunnel syndrome

Electrodiagnosis is the gold standard but sx generally used

Numbness, weakness, atrophy of the hand (all fingers but the pinky)

TYPING DOESNT CAUSE IT Insidious, sometimes work-related

Tx: splint, NSAIDs, corticone, surgery (open or endoscopic). Surgery found to be better than splinting overall in a study Injection of steroids better than oral steroids

Compression of median n at the wrist

Trigger finger

Tenosynovitis (inflammation of the fluid filled sheath synovium that surrounds the tendon

Pain, swelling, or sticking of the finger.

Tx: cortisone, surgery to release.

Fractures Instability SLAC Wrist

finger, hand, wrist, distal radius (Scapho-lunate advanced collapse)

due to either chronic untx scapohoid fracture or scapholunate dissociation

Saturday Night Palsy (hinted on test)

Reflexes: Brachioradialis absent or d, triceps usually normal

Due to compression of radial nerve Strength: weakness in wrist extension, finger extension (primarily MCP joints); triceps may be partially weak or normal. Sensory changes: abnormal on dorsum of hand

(hand over barstool wake up unable to move hand) Back (Lumbar) Arthritis Fracture Knee keeps knee from subluxing Positive anterior drawer sign indicates torn ACL ACL Degenerative or insidious. Most common in lumbar spine osteoporosis

Clipped from lateral side, causes unhappy triad: MCL, Medial meniscus, ACL Abnormal passive abduction indicates torn MCL

Anterior and Posterior refer to where they are attached on the TIBIA

Condition Patella Articular cartilage damage

Diagnose It

Pathophysiology OCD, Chrondromalacia, Fracture, Bone bruise

Pathology

Clinical Course usually subluxes laterally

Genetics/Epi

Treatment

Bakers cyst

usually from meniscal tear

cyst in the back of the knee. Between gastrocnemius medial head tendon and semimembranous muscles. In synovial sack of knee joint

Pigmented villonodular synovitis Tendon ruptures: Foot/Ankle Arthritis Fractures

thickened synovium patellar tendon or quad tendon (foot and ankle) Foot, ankle tx with surgery

LisFrancs injury

between 1st and 2nd metatarsal. 2nd metatarsal extends into tarsal bones.

Bunion

Wear tight shoes, whatever end up getting this huge bump on the side of your foot. Surgically removed.

Plantar fasciitis:

Inflamation of the plantar fascia

Diabetic ulcers, RSD, Charcot foot

Other Musculoskeletal Disorders from Robbins (not on content list) Condition Diagnose It Pathophysiology Ex: bone doesnt develop, fusion of 2 LOCALIZED developmental anomalies adjaent digits from problems in migration of Dystotoses (syndactyly), develop mesenchyme cells, condensations form extra bones Dysplasias Shortened proximal extremities with normal trunk, enlarged head Shortened limbs, relative macrocephaly, small chest cavity, bell-shaped abdomen DIFFUSE problem due to mutations in regulators of skeletal genesis FGFR3 constantly working to suppress cartilage in physis

Pathology Defect in nuclear proteins/transcription factors Craniorachischisis: Spinal column/skull dont close Defect in Hormones/Signal transduction

Clinical Course HOXD-13 TF forms extra digit between 3rd/4th digit, some syndactly

Genetics/Epi

Treatment

Uncommon

Achondroplasia

AD (point mutation on short arm of Chr 4)

Thanatophoric dwarfism Type 2/10/11 Collagen Disease (collagens in hyaline cartilage Mucopolysacc haridoses

Defect in extracellular structural proteins

Lethal (from respiratory insufficiency)

1/20,000 live births

Early joint destruction

Defects in folding/degradation of molecules Lysosomal storage diseases ( enzymes to degrade dermatan sulfate, heparin sulfate, keratin sulfate) Defects in metabolic pathways osteoclast bone resorption causes skeletal sclerosis. Carbonic anhydrase II deficiency: Osteoclasts/renal tubule cells need it to acidify the environment prevents digestion of bone. PTH production

Pt short stature, chest wall abnormal, malformed bones Infantile form AR, lethal or causes major problems with d hematopoiesis (less marrow space) Adult form: AD, benign, some anemia.

Mesenchymal cells (*chondrocytes*) most affected cause a lot of problems in hyaline cartilage

Osteopetrosis (marble bone disease/AlbersSchonberg)

Morphology: no medullary canal in bones, long-bone ends are bulbous. Primary spongiosa persists. Woven bone Effect of PTH levels: Activates osteoblasts to release pro-osteoclast signals

Brittle bones (easily fracture)

Bone marrow transplant can help

Hyperparathyroidis m

The whole body is affected cortical bone affected > cancellous bone

Severe/untreated long-term PTH usually diagnosed early Osteitis fibrosa cystica (von Recklinghause n disease) X-ray pattern along radial aspect of middle phalanges of index/middle fingers Primary: autonomous hyperplasia or tumor (adenoma) Secondary: caused by prolonged hypocalcemia state tend to have milder skeletal abnormalities

Brown tumor: mass of reactive tissue from microfractures/secondary hemorrhages/ingrowth of fibrous repair tissue Peritrabecular fibrosis bone cell activity

Subperiosteal resorption => thinned cortices/lost lamina dura around teeth

Observe cortical cutting cones with osteoclasts boring through (enlarge haversianvolkmann canals) looks like railroad tracks (dissecting osteitis) d bone density (osteopenia)

treat the hyperparathyroidism (sx will regress or disappear!)

Renal Osteodystrophy

skeletal changes with chronic renal disease

Phosphate: failure to excrete phosphate secondary hyperparathyroidism Calcium: failure to convert 25-(OH)D3 to 1,25 (OH)D3 (less Ca absorbed) PTH: less 1,25 (OH)D3 to suppress parathyroid, less degradation/excretion of PTH Metabolic acidosis: stimulates bone resorption, release of calcium hydroxyapatite from matrix Aluminum deposition (dialysis solutions contain it): interferes with calcium hydroxyapatite deposition osteomalacia results B-microglobulin in serum with long-term hemodialysis causes amyloid deposition in bone!

often a mixed pattern of disease osteoclast resorption (looks like osteitis fibrosa cystica) Delayed matrix mineralization (osteomalacia) Osteosclerosis Growth retardation Osteoporosis -turnover osteodystrophy: bone resorption/formation (but more resorption occurs) -turnover/aplastic disease: little osteoclast/osteoblast activity, sometimes osteomalacia

Function: stimulates intestinal absorption of Ca/PO4, works with PTH to mobilize Ca from bone, stimulates PTHdependent reabsorption of Ca in distal renal tubules, likely helps osteoclasts differentiate from monocytes Vitamin D

Ricketts: children have deranged bone growth, producing skeletal deformities Overgrowth of epiphyseal cartilage from inadequate calcification, poor maturation of cartilage cells. Irregular cartilage project into marrow cavity, osteoid matrix is deposited on the weird cartilage. Osteochondral junction enlarges, expands laterally. Capillaries/fibroblasts overgrow in the area from microfractures/stresses on the crappy bone. Skeleton gets deformed from loss of structural rigidity of developing bones Clinical picture: Frontal bossing, Rachitic rosary, pigeon breast deformity, Harrisons groove (diaphragm pulls rib cage bottom in), lumbar lordosis, bowing of legs Osteomalacia: Vitamin D deficiency causes less intestinal absorption of Ca/PO4, PTH will stimulate more loss of Ca from bone to restore blood levels. Adults have disorganized remodeling of bone. Bone contours not affected, but bone is weak/vulnerable to fractures (especially vertebral bodies, femoral necks). Histological: thickened matrix with normal trabeculae. Eventually, difficult to differentiate from other osteopenias Hypocalcemic tetany

Musculoskeletal Bugs
Bug Name Streptococcus sp (Groups A/B): A=Strep pyo, B=Strep agalactaciae Staining characteristics G+ cocci in chains Facultative anaerobes Beta hemolytic (bacitracin sensitive) Glucose fermenters Catalase neg, coagulase neg Clinical Features Osteomyelitis, Joint Infection Epidemiology Group B in 10-35% of all healthy adults (intestine, vagina, rectal) causes problems in NEONATES

Virulence Hyaluronic acid capsule M protein Streptolysin O, S DNAses Streptokinase A/B (lyses blood clots) Hyaluronidase (degrades CT) Exotoxins (super ags)
Forms biofilms, Capsular polysaccharide (anti-phag/chemotactic), Slime layer Protein A (Binds IgG Fc, prevents opsonization), MSCRAMM SuperAg toxins (TSST-1) Hyaluronidase (hydrolyzes CT) Penicillinase Staphylokinase/fibrinolysin Adhesin promoting collagen attachment (osteomyelitis, septic arthritis) Most are resistant to 1st generation cephalosporins, ampicillin. May be susceptible to 2nd/3rd generation

Staphlococcus aureus

G+, cocci in clusters Beta hemolytic, yellow colonies on blood agar Ferments mannitol on MSA, salt tolerant Facultative anaerobe Catalase +, Coagulase +

Osteomyelitis 90% due to S. aureus! Joint Infection (Bursitis) 80% is due to staphylococcus.

Transmission: Autoinnoculation (Normal flora in nasal mucosa/skin), Surgical wounds, Lungs of CF pts, , Hands Risk: surgery/break in skin, tampons, ventilators, catheters, severe neutropenia, CF, IV drug use, Chronic granulomatous disease

Enterobacter sp

G- rods Facultative anaerobe Ferment lactose

Osteomyelitis, Joint Infection

Link to contaminated parenteral fluid solutions Normal GI tract flora (way less than E coli)

Haemophilus influenzae

G- coccobacilli Obligate parasite (faculatative anaerobic) Chocolate agar (requires factor X & V, CO2) Oxidase + G-, kidney-bean shaped diplococci (in PMNs) No capsule, non-maltose fermenting Intracellular, aerobic Grows on Thayer-Martin Oxidase/catalase +

Osteomyelitis, Joint Infection Septic arthritis: joint pain, swelling, d mobility.

Normal flora (20-80%, nasopharynx) o Unimmunized children 6-18 months most vulnerable - NEONATES o Most people acquire Ab by age 10, so infection rare in adults. An STD (2nd most common) More in males (females more frequently asx carriers) Highest rates in ages 15-30, unmarried, low SE status

Type B Polysaccharide Capsule (directly invades blood capillaries) IgA protease Attachment pilli Ampicillin resistance

Neisseria gonorrheae

1st Stage: Arthritis dermatitis syndrome: Joint/tendon pain is most common in early infection. Migratory polyarthralgia, especially of knees, elbows, more distal joints, Tenosynovitis: flexor tendon sheaths (wrist), Achilles tendon ("lovers' heels"). Dermatitis: maculopapular lesions, often w/hemorrhagic component. 5-40 lesions, peripherally located, painful before visible. Fever common, but temp usually <39C. 2nd Stage: Septic Arthritis: skin lesions have disappeared; blood culture results are nearly always negative. Most commonly ends up in the knee.

Pili with high ag variation (antiphagocytic, adhesive to mucosa) IgA Protease LOS (creates sialic acid capsule) Upregulates catalase in phagocytes Receptors to scavenge FE from transferrin/lactoferrin

Musculoskeletal Drugs
Drug Name Mechanism of Action weak nonselective COX inhibitor in presence of peroxides inhibits COX3 (COX1b) in brain. Inhibits uptake of NE and 5HT, Weak Mu agonist Mech unclear, but T cells affected most Non-selective NSAID Propionic acid derivative Reversible COX inhibition (COX1 and 2) Non-selective NSAID Acetic acid derivative reversible COX inhibitor Selective NSAID - COX-2 Inhibitors. Sulfur group selectively binds COX-2, excludes COX-1 Purine analog Reduces production of uric acid by competitively inhibiting Xanthine Oxidase (the last 2 steps of uric acid biosynthesis) Xanthine and hypoxianthine are more soluble, less likely to precipitate in joints Binds tubulin, depolymerizes it disrupts granulocyte mobility Colchicines Blocks cell division (binds mitotic spindles) Inhibits synthesis/release of LTs Diazepam Benzodiazepine Agonist at GabaA receptor/Y-aminobutyric acid target Unknown mech Cyclobenzaprine (Aka cyclone, mellow yellow) Appears to affect locus ceruleus to inhibit NE uptake, appears to inhibit alpha motor neurons in ventral horn of SC Beta lactam antibiotic work like penicillin to disrupt cell membrane Blocks muscle spasms Skeletal muscle relaxant Oral admin Enhances GABA effects Skeletal muscle relaxant, MS, cerebral palsy Oral admin Lipophilic, go through entire body Metabolized in liver Excreted in urine, crosses placenta Gout Acetominophen Effects: Analgesic (non-opioid) analgesia, antipyretic equal to aspirin no antiinflammatory (if any, weak) or antithrombotic fx Analgesic (non-opioid) Synthetic codeine analog, Anti-inflammatory, immunosuppressive analgesia antipyretic antiinflammatory Anti-inflammatory, analgesic, antipyretic antiinflammatory, analgesic antipyretic fx equivalent to aspirin and ibuprofen no antithrombotic fx Gout drug of choice if hx of kidney stones or if creatinine clearance <50 mL/day Oral admin (completely absorbed) Feces/urine excretion 1 dose daily = ok (alloxanthine metabolite has long life) Whys it Used? Tx mild pain & fever, fever from virus Mild arthritis - Analgesic Pharmokinetics rapidly absorbed from GI, peak plasma conc in 30-60 min, metabolized in liver. Distributes to peripheral tissue and CNS. Renal excretion. plasma life = 2-3hr Major Side Effects well tolerated by GI overdose: liver tox w/ liver failure, enhanced by chronic EtOH use high chronic use associated with chronic renal failure Nausea, vomiting, dizziness, dry mouth, sedation, headache, seizures Hypercholesterolemia, cataracts, osteoporosis, HT w/prolonged use Gastric irritation, nausea, dyspepsia, bleeding, peptic ulcer disease. Acute renal failure in patients at special risk: volume depletion, preexisting renal dx, CHF, hypotensive. Aspirin alt (children) Toxicity limits use in tx for gouty arthritis, Ankylosing Spondylitis, osteoarthritis of hip less GI tox compared to nonselective COX inhibitors some renal tox, diarrhea, dyspepsia, abdominal pain CV toxicity very expensive Hypersensitivity (rash) 3% Acute gout attack (give w/colchicine & NSAIDs at beginning) Nausea, Diarrhea Affects metabolism of 6-mercaptopurine, azathioprine (need to reduce their doses if given w/ Allopurinol) Avoid if pt has creatining clearance <50 mL/min. Nausea, vomiting, abdominal pain, diarrhea Myopathy, neutropenia, aplastic anemia, alopecia. CI pregnancy, hepatic/renal/CV disease Drowsiness/confusion Physical dependence Caution needed if liver disease, glaucoma Drowsiness, depression, HA Respiratory depression, d muscle function Dry mouth Vision problems High dose: Anticholinergic, ataxia CI w/ MAOIs CI if penicillin allergy (likely to be allergic to this too)

Tramadol Corticosteroids (prednisone, methylprednisolone) Ibuprofen Naproxen

Use for mild to moderate pain RA (immunosuppressive, antiinflammatory) Pain & inflammation - trauma, infection, autoimmune disorder, neoplasms, joint degeneration -RA, OA, AS Pain/inflammation

Take PO, Wide distribution. Liver metabolism, renal excretion

Indomethacin

Celecoxib

Osteoarthritis, Rheumatoid arthritis. Analgesic not effective post surgery. Protective against colon carcinogenesis?

Take PO, gut absorption. Liver metabolism (Cyt P450). Excreted in urine and feces

Allopurinol

Prophylaxis to reduce occurrence of acute attacks, relieves pain give within 24-48 hrs of attack onset

Oral admin (rapid absorption by GI) Feces/urine excretion (unchanged)

First Generation Cephalosporins (Cephalexin, cephalothin)

G+ cocci and G- rods Resistant to penicillinase of staph, Active against PEKS: Tx for osteomyelitis

IV/IM (poor oral absorption) Cross the placenta Dont go into the CSF Urine elimination

Proteus, E coli, Klebsiella, Staph Cephazolin penetrates bone well Inhibit replication of bacterial DNA by interfering w/action of DNA gyrase and topoisomerase Bactericidal Levofloxacin = 3rd generation osteoclastic bone resorption: o Inhibits osteoclastic proton pump needed to dissolve hydroxyapatite, o osteoclastic formation/activation, o osteoclastic apoptosis, o cholesterol biosynthetic pathway needed for osteoclast function Reduces bone resorption but less effective than biphosphonates Neisseria G- (enterobacteriaceae, pseudomonas, H flu, Moraxella, Legionella, Chlamydia, Mycobacteria); Some G+ (newer ones like levofloxacin!) Ingesting with antacids (Al, Mg, Zn, Fe) can interfere w/absorption Distribute well to all tissues and body fluids (bone ) Renal excretion Diarrhea/nausea/vomiting HA/dizziness Phototoxicity, nephrotoxic Cartilage erosion, can cause ruptured tendons (fluoroquinolones hurt attachments to your bones) Can serum levels of warfarin, caffeine, cyclosporine Diarrhea, abdominal pain, musculoskeletal pain. Some cause esophagitis/esophageal ulcers Osteonecrosis of jaw Intranasal admin Parenteral form rarely used for osteoporosis

Fluoroquinolones (Loveofloxacin)

Tx for osteomyelitis

Biphosphonates (etidronate, risedronate, alendronate, ibandronate, pamidronate, tiludronate, zoledronic acid)

Preferred agent to prevent/treat postmenopausal osteoporosis

Tx for osteoporosis, Pagets, bone metastases, hypercalcemia

Oral admin, without food (IV available) Bind hydroxyapatite in bone (cleared over hrs to yrs) Renal excretion

Calcitonin

But RELIEVES PAIN of osteopathic fracture spinal bone density, s risk of vertebral fracture. Should reserve for pt w/high fracture risk or who cant tolerate other txs

Tx for osteoporosis

Rhinitis Pagets pts have resistance (if long use) risk of osteosarcoma in rats Safety/efficacy not evaluated beyond 24 months.

Teriparatide

Recombinant segment of PTH Stimulates bone formation.

Tx for osteoporosis

Subcutaneous admin

Sufasalazine (a DMARD)

PABA analog to occupy dihydropteroate synthetase May inhibit phospholipase A2 and platelet aggregation, Membrane stabilization, effects on immune system, Antioxidant activity Doesnt slow joint damage when used alone have to use in combo

Hydroxychloroquine (a DMARD)

Rheumatoid arthritis early/mild RA in combo w/ hydroxychloroquine and methotrexate Rheumatoid arthritis early/mild RA tx combo w/methotrexate & sulfasalazine Also used for malaria

Not absorbed orally or as suppository Onset takes 1-3 months

Leukopenia

Renal toxicity (?)

Methotrexate (a DMARD)

Immunosuppressant (inhibits DHFR used to make folate)

Slows appearance of new erosions in joints on radiographs Use alone or in combo

Rheumatoid arthritis (or psoriatic)

Given 1X per week

Infliximab

Immune modulator Chimeric IgGk monoclonal ab (human and murine regions) *Binds human TNFa (neutralizes it)*

Cant use alone do combo w/methotrexate (body will develop anti infliximab ab if not in combo)

Rheumatoid conditions, psoriasis (derm and arthritis), ulcerative colitis, Ankylosing Spondylitis, Crohns

IV admin, 9.5 day life

Doses needed for RA are much lower than cancer use so side effects minimal, not like those assoc w/ cancer use. Mucosal ulceration, nausea Cytopenias, cirrhosis, acute pneumonialike syndrome if chronic use Fever/chills/pruritus, urticaria Predisposed for infection Lymphoma? Leukemia, neutropenia, thrombocytopenia, pancytopenia

Robbins Notes: Chapter 26 Bone/Joints/Soft Tissue Tumors: Normal bone physiology: o Osteoprogenitor cells: undergo cell division, pluripotent, TF a1 stimulates them to make osteoblasts o Osteoblasts: build bone. Cell receptors for PTH, Vit D, estrogen, growth factors, etc. Life span = 3 months, then become osteocytes o Osteocytes: communicate via canaliculi. Can detect mechanical forces and induce certain signaling paths o Osteoclast: bone resorption cells. From same cells that make monocytes/macrophages. Formation stimulated by IL 1/3/6/11, TNF, GM-CSF, M-CSF, Rank RankL binding (blocked by osteoprotegerin OPG) Mature osteoclasts = form resorption pits (Howship lacunae) As osteoclasts break down bone, the acidic environment releases growth factors to stimulate osteoblasts! Remodelling happens all the time (10% of skeleton replaced each yr) Peak bone mass at 30s, then declines o Bone proteins: Type 1 collagen: 90% of organic bone wt Woven bone in fetal skeleton, growth plates. o Quickly produced, resists forces from all directions equally. o Presence in adult = pathological state (like rapid repair from a fracture, around infection, makes up a tumor) Lamellar bone Slow growing, stronger 4 types: circumferential/concentric/interstitial (in cortex only) and trabecular (makes up long bones) Noncollagenous proteins from osteoblasts Osteocalcin: unique to bone. Se/sp marker for osteoblast activity. Cell adhesion proteins: osteopontin, fibronectin, thrombospondin Ca-binding proteins: Osteonectin, bone sialoprotein Mineralization proteins: Osteocalcin Enzymes: Collagenase, alkaline phosphatase Growth factors: IGF-1, TGF-B, PDGF Cytokines: Pg, Il-1/6, RANKL Bone growth/development Long bones: Homeobox genes: encodes TF for differentiation Wk 8: Endochondral ossification starts, periosteal region is building cortex (primary area of ostification) Chondrocytes remain at the physis (growth plate) regulated by Indian hedgehog gene and PTHRH Primary spongiosa: cartilage core, bone layer around it Clavicles, parts of the cranium: Intramembranous formation osteoblasts only make the bone (bone deposited on pre-existing surface appositional growth) o o