musculoskeletal Flashcards
• Normal skeletal mm:
o Muscle cells = muscle fibers.
o Each fiber has 100-1000s myofibrils
o Exercise: no ↑ #fibers, ↑# myofibrils =hypertrophy
o atrophy from disuse: ↓ #myofibrils in each fiber
• mm atrophy (disuse):
o disuse vs neurogenic
o Disuse: generalized vs localized
o Generalized, ex: prolonged immobilization in bed
o Localized, ex: cast immobilization for fracture
o Mb masked as ↑fat develops bw fibers
• Neurogenic atrophy:
o = ↓ mm mass dt damaged nerve supply
o Mb dt any neuropathy
o ↓nerve stimulation → mm atrophy, motor fibers necrose
o unusual for all motor fibers of a muscle group to be destroyed, unless complete transection
o usu normal fiber mixed w atrophied mm
o mm may recover if intact neurons can re-innervate
o ssx: often contractures, dt opposing mm w ↓ resistance
• Muscular dystrophy:
o Genetic dzs, progressive mm damage and weakness
o >100 forms, mc Duchenne’s & most serious
o Other: Becker’s, limb-girdle, myotonic dystrophy
o defects in mm proteins, necrosis, loss fibers
o st cardiac and sm also affected
• MD ssx:
o Progressive mm weakness and wasting o Poor balance o Frequent falls o Difficulty walking o Waddling gait o ↓ROM o Muscle contractures
• Duchenne’s ssx:
o general mm weakness and wasting , usu 1st pelvis, 2nd shoulders/upper arms, upper legs
o Eventually → all voluntary muscles
o Shoulders held back when walking, sway back, belly sticks out
o Thin weak thigh, butt; thick lower leg (fat)
o Knees bend back to take weight
o Toe walking, foot drop
o Poor balance (fall), clumsy walking
• Duchenne’s epidem, etio, physio:
o XLR (M»F)
o Onset 2-6, wheelchair by 12, death by 20s
o def dystrophin, protein in skeletal mm cell membrane
o → ↑Ca enters cell → ROS > cell’s oxide-scavenging enzymes can handle
o oxidative stress → cell death → necrosis →fibrosis → degenerate, adiposis
o late stage: mm mb entirely replaced w fat
o →st hard to dx, bc fat hides visible mm atrophy= pseudohypertrophy
• Duchenne’s micro:
o Bx: fiber degeneration and atrophy, some regeneration and hypertrophy
o Early: scattered groups inflam cells
o Immuno: Anti-dystrophin Ab reveals lack of protein
• Myasthenia gravis, epidem:
o AI neuromuscular dz, fluctuating muscle weakness and fatigability
o Weakness dt Abs block AChRs at post-synaptic NMJ (90%), may block or destroy R (C or endocytosis), membrane lysis
o Normal: Ach → influx Na, Ca → contraction
o Usu F ↓40, or ppl 50-70, or any age, any race
o Risks: F, 20-40, FHx, D-penicillamine (drug-induced), other AI
• Thymoma assoc w MG:
o Abs from plasma cells, activated by T-helper cells (thymus)
o → 10% have thymoma (esp old M), rare ↓40
o Many have thymus follicular hyperplasia (F>M)
o Paradoxically, esp young w/o thymoma benefit from thymectomy
o W thymoma,less likely to improve sxs
• MG ssx:
o onset slow or rapid
o ssx come and go over time, st dx later; easy fatigability, weakness better rest, worse exertion =hallmark
o mc: innervated by brainsterm nuclei: mm of eye, eyelid, facial, chew, speech, swallow
o → ptosis (1st), diplopia, can’t chew, dysphagia, dysarthria
o waddling gait, weak arms, hands, fingers, legs
o st: mm of breathing (dyspnea), neck, limbs
o ↓resp (myasthenic crisis), need ventilation; mb trigger by infx, fever, meds, stress
o → death
o Heart never affected
• MG, epidem, tx:
o sxs improve w anticholinesterase drugs, neostigmine, pyridostigmine (4 hrs) → strengthen
o Or immunosuppressive to ↓AI: prednisone, cyclosporine, mycophenolate mofetil, azathioprine (effects in wks-mos)
o Often combo
o Serious: plasmapheresis to remove Ab, or IV Ig (a-Ab), only lasts wks
o Thymectomy improves sxs >50%, st cure (but not definitive), st effects in wks-yrs
• Mg px:
o Mild-severe
o Tx: normal life expectancy, except w malig thymoma (need chemo)
o QoL varies w severity
o drugs often ↓ effectiveness over time (cholinesterase inhibitors)
o or severe side effects (immunosupressants)
o 10% have thymoma (thymectomy effective, long-term remission)
o Usu need tx for life
o not a progressive dz
o st sxs ↓ after 3–5 yrs
• MG dx:
o Hx, PE, 2 (+) dxtests: preferably sero and electro-dx
o Dx: ↑ strength w edrophonium (Tensilon test) or neostigmine
o Abs, sens 90%, but 50% in ocular myasthenia
o Repetitive nerve stim studies
• MG micro:
o Micro: Mb normal or myofiber atrophy, lymph aggregates in endomysium
o Severe: mb myonecrosis, pale, atrophic
o Non-dx (for research):
o EM: abn motor end plates, receptor infolding, loss post-synaptic membrane, simplified, few wide folds, no branching. wide synaptic cleft
o Immuno: IgG on NMJ
• Lambert-Eaton syndrome, epidem:
o Aka Lambert-Eaton myasthenic syndrome
o progressive mm weakness, usu 1st upper legs and arms
o 60% assoc w small cell lung CA (sx onset before CA detect)
o 3% of SCLC pts
o Other CA assoc: lymphoma, non-Hodgkin’s, T-cell leukemia, prostate, thymoma
o St assoc AI dzs
• LES etio, ssx, dx:
o Abs against presynaptic Ca channels in NMJ, inhibits the normal release ACh
o ↑strength w initial exertion and mild exercise (allows for Ach to buil-up, recycle)
o Worse w longer exertion
o Dx: CXR lung CA, Abs, nerve conduction studies (incremental response in repetitive nerve stim)
• Idiopathic inflammatory myopathies
o muscle-specific AI dzs
o mc: Dermatomyositis, polymyositis, inclusion body myositis
o AI inflam and vascular damage to striated muscle
o Dx: hx, bx (definitive), EMG, MRI
o Ssx: weak neck extensor, diff hold head up; Dysphagia, aspiration if pharyngeal and esophageal mm
• Dermatomyositis:
o CT dz, inflam skeletal mm and skin
o Usu adults, or kids 5-14
o Unk etio, mb viral →AI
o 50% dt paraneoplastic syndrome (CA)
o C-mediated damage vessels in mm and skin
o → mm atrophy, ischemia, necrosis, lymphocytic inflam
• DM dx:
o Hx weak, skin
o Labs: ↑CPK, ESR
o EMG: membrane irritability, ↓amplitude and duration of motor unit AP, chronic denervation-reinnervation
o Bx: mixed B- and T-cell perivascular inflam infiltrate, Perifascicular muscle fiber atrophy
o Necrosis, regeneration
• DM ssx:
o characteristic periorbital heliotrope rash (mb before weakness)
o =symmetric, purple-red, macular eruption of eyelids, periorbital tissue, malar area, forehead, nasolabial folds
o Gottron’s sign: purple red papular rash over dorsal MCPs and IPs
o Shawl sign: violaceous/erythematous rash over deltoids, posterior shoulders, neck
o V sign: rash on anterior neck, upper chest
• Polymyositis:
o BL proximal, progressive muscle weakness, pain, tender (mb confused w PMR)
o adults, very rare ↓20
o mc proximal limbs (legs 1st), neck flexors; distal weakness late
o never ocular mm (unless isolated orbital myositis, EOM)
o no skin involved
o Dysphagia dt oropharyngeal and esophageal, 1/3, poor px
o Weakness: can’t sit up, raise arms
• PM tx, px, micro:
o immunosuppressive → lifelong tx
o 5-yr survival >80%
o Mb death dt severe weakness, pulm involvement, cardiac involvement, assoc malig, comp of immunosuppress tx (infx)
o Mm fibers pale & enlarged, M0 invasion (complete by late stage)
o lymphocytic inflame, mostly cytotoxic T8 lymphs
• Inclusion body myositis, epidem, px:
o Rare, slowly progressive (mos-yrs) weakness, mostly arms and legs (distal and proximal)
o T-cell mediated, Ags that invade muscle fibers → mm inflam → degeneration
o Usu >50
o mc acquired muscle do seen in >65
o CK usu 10x normal, may fall later
o Often mis-dx as PM
o Poor response to tx (if PM poor response to tx, think IBM instead)
• IBM bx:
o Focal areas of WBCs, inflammatory cells
o vacuoles in muscle
o deposits of amyloid-related proteins in mm cells
o inclusions: build-up abn proteins, tau, beta amyloid, ubiquitin
• Rhabdomyomas:
o benign tumors of striated mm
o usu round mass in neck
o Adult: rare, 90% in head and neck
o Histo: well-diff large cells like normal, deeply eosinophilic polygonal, small peripheral nuclei, st intracellular vacuoles
• Non-head and neck rhabdomyomas:
o Genital: usu vag or vulva in youger F. usu asx. dyspareunia. fibroblast-like cells, clusters of mature cells, distinct cross-striations, matrix w varying collagen and mucoid. polypoid or cyst-like mass
o Cardiac: hamartoma, usu kids, often congenital, detected on prenatal US. Myocardium of ventricles, IV septum. Assoc w tuberous sclerosis of brain, sebaceous adenomas, other hamartomas of kidney, etc
• Rhabdomyosarcoma:
o Malign, from embryonic mesenchymal cells (→ skeletal mm)
o Mc soft tissue tumor in kids (50%)
o 3rd mc solid malig in kids (outside CNS), 5-15%
o 90% ↓25, 70% ↓10
o Many sub-types, distinct histo; major: embryonal and alveolar
o Other: botryoid, spindle cell, undifferentiated (anaplastic)
• Rhabdomyosarcoma histo:
o invade locally, ill-defined margins
o fibrous histiocytoma
o pleomorphic cells, vary in size and shape
o poor diff, st anaplastic (hard to determine cell origin)
o interweaving bundles of spindle shaped cells, elongated hyper-chromatic nuclei
o many mitoses
• RMS ssx, tx:
o rapid onset UL proptosis, edema, redness
o can enlarge dramatically in d-wks
o (RMS in orbit not from differentiated muscle cells, but primitive undifferentiated mesenchyme, anywhere in orbit)
o Usu head (1/3 orbit, face, scalp), neck, GU, or anywhere (limbs, any striated mm)
o Head and neck esp in kids
o Tx: surgery, local irradiation, chemo
• Mechanical functions of bone:
o Protection: internal organs, skull, ribs o Shape: support body o Movement (biomechanics): w skeletal muscles, tendons, ligs, jots; 3D o Sound transduction: overshadowed hearing
• Biochemical reserve fxn of bones:
o Blood production: marrow in medullary cavity of long bones and interstices of cancellous bone
o produces blood cells (hematopoiesis)
• metabolic fxns of bone:
o Mineral storage: Ca & P
o GF storage: insulin-like GF, transforming GF, etc
o Fat Storage: yellow bone marrow, fatty acids
o Acid-base balance: absorb or release alkaline salts
o Detox: store heavy metals, foreign elements, remove from blood; can later be gradually released for excretion.
• Endocrine fxns of bone:
o PO4 metabolism via fibroblast GF-23 (FGF-23) → KD, ↓ PO4
o Osteocalcin: blood sugar and fat deposition. ↑ insulin secretion, sensitivity, # Beta cells; ↓ fat stores
• Osteogenesis imperfecta
o Aka brittle bone dz; genetic
o defective CT dt ↓ normal type-1 collagen (forms bone matrix)
o 8 sub-categories, many not compatible with life
• Types of bones in humans:
o Long: shaft (diaphysis). mostly compact bone, some marrow in medullary cavity, and spongy bone. Most limbs, fingers, toes (not wrist, ankle, kneecap)
o Short: cube-shaped, thin layer compact bone around spongy interior. wrist and ankle, sesamoid bones
o Flat: thin, curved, two parallel layers of compact bones around spongy bone. skull bones, sternum.
o Irregular: do not fit into above categories. thin layers of compact bone around spongy interior. Spine, hips
o Sesamoid: embedded in tendons. hold tendon further away from jt, increase leverage of muscle. Patella, pisiform
• Lamellar bone formation:
o Compared to woven bone, more slowly
o orderly deposition of collagen fibers restricts formation of osteoid to ~1-2 um/d
o requires flat surface to lay collagen fibers in parallel or concentric layers
• Legg–Calvé–Perthes syndrome:
o idiopathic avascular osteonecrosis of epiphysis of femoral head
o flattened femoral head, not in correct position
o →interrupt blood supply to femur head, close to hip jt
o artery of ligamentum teres femoris closes too early, no time for medial circumflex femoral a to take over
• rickets:
o = softening of bones in children, may →fractures, deformity
o Usu dt vit D def, or ↓Ca in diet (either dt chronic severe V/D)
o Common childhood dz in many developing countries, dt severe malnutrition (famine, starvation in early childhood)
o May occur in adults
• Osteomalacia:
o Similar to rickets, in adults
o Usu dt Vit D def
• deformities seen with rickets:
o related to age when affected
o Toddlers: Bowed legs (genu varum)
o 1.5-4: mild genu varum
o Kids >4: Knock-knees (genu valgum) or “windswept knees“
o Rachitic rosary: Prominent knobs of bone at costochondral jts, seen under skin of rib cage
• Genu valgum in kids:
o May be unrelated to Vit D def and rickets
o Usu 2-5, often corrected naturally as they grow.
o May worsen w age if underlying dz or rickets, obesity
• Osteoporosis, epidem:
o =low bone mass and structural deterioration (porous)
o → fractures, esp hip, spine, wrist (any bone)
o F>M 4:1, >50 50% F, 25% M in lifetime
o all ethnic backgrounds: white & Asian > Hispanic > black
• osteoporosis etio:
o Mb dt generalized ↓bone mass, or more localized process (bone in a casted limb)
o Accelerated: malabsorption dos, hyperthyroid, hyper-parathyroid
o Generalized:
o 1st: osteopenia (bone thinning) dt ↑ age or menopause
o 2nd: ↓ bone mass dt other dos, meds, malabsorption, immobilization
• Osteoporosis work-up:
o X-ray: only reliable if at least 30-40% ↓bone mass
o NOT dx: Serum Ca, P, ALP
o Dx: DEXA or CT
• 2nd osteoporosis:
o endocrine dos: Hyperparathyroid, Hypo/hyperthyroid, Hypogonadism, Cushing’s, Addison’s, DM
o Postmenopausal: hormone dependent acceleration of ↓bone; ↓E → cytokines (IL-1, IL- 6, TNFa) → ↑osteoclast activity
o Any GI do that causes malabsorption
o Malnutrition, Vit D def, Vit C def
o Liver dz
o Neoplasms: multiple myeloma
o Any ectopic PTHrP or ACTH
o Drugs: corticosteroids, anticonvulsants, anticoagulants, chemo, alcohol
• Risk factors for osteoporosis:
o F o Thin, small frame o Elderly o FHx o PMHx fracture > 50 o Current documentation of ↓bone mass o Hx fracture in 1st degree relative o ↓E dt menopause, esp early or surgically induced o Amenorrhea o ↓T in M o Anorexia nervosa o ↓lifetime Ca intake o Vit D def o inactive lifestyle o Current cigarette smoking o ↑ alcohol o Caucasian or Asian (but other races, too) o Meds: corticosteroids and anticonvulsants
• Postmenopausal osteoporosis:
o 2% cortical, 9% trabecular bone loss per yr in 1st decade
o In 30-40 yrs, up to 35 % cortical, 50 % trabecular bone loss
o 50% pm F get osteoporotic fracture (vs. 1 in 40 M)
• Osteoporosis fractures in US:
o 1.5 million/yr o 700,000 vertebral (bodies shortened by compression fractures) o →kyphosis (hunch back) o > 300,000 hip o 250,000 wrist o 300,000 other
• Paget’s dz of bone:
o Aka osteitis deformans
o high bone turnover w ↑osteoclast and osteoblast activity
o focal process, variation in stage in separate sites
o ↑calcification, ↑bone deposition in skull, pelvis, tibia, femur
o Bone pain, deformities, fractures common
o Labs: ↑ ALP
o Paget disease is a focal process with remarkable
