3 types of bone cells:
osteocytes
osteoblasts
osteoclasts
3 general bone functions:
mechanical
biomechanical reserve
metabolic
What are the mechanical functions of bones?
protection
shape
movement
sound transduction (hearing)
What is the biomechanical reserve function of bones?
blood production in the marrow
What are the metabolic functions of bones?
mineral storage growth factor storage fat storage acid-base balance detox (store heavy metals) endocrine function (FGF, osteocalcin)
Genetic bone d/o referred to as brittle bone dz:
osteogenesis imperfecta (OI)
born w/defective CT d/t deficiency of type-I collagen
8 subcategories, most incompatible with life
Idiopathic avascular osteonecrosis of the epiphysis of the femoral head leading to an interruption of the blood supply of the head of the femur close to the hip joint:
Legg-Calvé-Perthes syndrome
aseptic necrosis not d/t trauma or septic dz
Softening of bones in children potentially leading to fractures and deformity, and among the most frequent childhood dz in many developing countries:
rickets
MC cause of rickets:
Vitamin D deficiency
also:
calcium deficiency
mb 2° to severe diarrhea/vomiting
Toddlers who contract rickets get a __________ deformity, vs older children who get ______________.
toddler - genu varum
children - genu valgum OR “windswept” - both same direction
Prominent knobs of bone at the costochondral jts of rickets pts are known as:
rachitic rosary - beading of the ribs
d/t deficiency of calcium -> lack of mineralization -> overgrowth of cartilage
Dz characterized by low bone mass and structural deterioration of bone tissue:
osteoporosis
mb generalized loss or localized (i.e. casted limb)
The inc porous nature of osteoporotic bone leads to fragility and inc susceptibility to fractures, esp of the ____, _____, and _____, although any bone can be affected.
hip, spine, and wrist
affects ~10 million in the US [F:M 4:1]
1° osteoporosis is a term used to describe _________ d/t advanced age or menopause.
osteopenia (bone thinning)
2° osteoporosis implies dec bone mass d/t:
- medications (corticosteroids, anticonvulsants, anticoag, chemo, EtOH)
- malabsorption (malnutrition, low vit C or D)
- immobilization
- medical conditions
- hyperparathyroidism
- hypo/hyperthyroidism
- hypogonadism
- Cushing’s
- Addison’s
- DM
- liver dz
- neoplasm (mult myeloma)
- ectopic hormone prodution (PTHrP, ACTH)
T/F: Osteoporosis cannot be reliably detected by plain x-rays until 15% of bone mass has been lost.
False
actually can’t see reliably until 30-40% loss!
T/F: Serum calcium, phosphorus, or alk phos can be measured to dx osteoporosis.
False - serum levels are buffered by bone catabolism, and are NOT diagnostic
Diagnostic testing for osteoporosis:
DEXA scan (dual-energy x-ray absorptiometry)
T/F: Postmenopausal osteoporosis is characterized by a hormone dependent acceleration of bone loss primarily d/t estrogen deficiency.
true
Diminished estrogen results in secretion of cytokines:
which are in large part responsible for __________ activity.
IL-1, IL-6, TNF-alpha
inc osteoclast activity
Risk factors for osteoporosis:
- female sex
- thin / small frame
- low bone mass
- advanced age
- FHx
- PMHx of fracture after 50 y.o.
- Hx of early fracture in 1st degree relative
- estrogen deficiency d/t menopause (esp early/surgical)
- amenorrhea
- anorexia nervosa
- low testosterone in males
- low lifetime calcium intake
- Vit D deficiency
- sedentary lifestyle
- cigarette smoking / excessive EtOH
- Caucasian / Asian descent
Exaggerated curvature of the thoracic spine that results in a rounded or hunched back:
kyphosis
commonly seen in pts w/osteoporosis d/t compression fractures of vertebrae
Dz characterized by high bone turnover with accelerated osteoclast and osteoblast activity:
Paget’s dz (osteitis deformans)
Inc calcification of bone - predilection for inc bone deposition in skull, pelvis, tibia, femur
Clinical signs of Paget’s dz:
Labs:
- bone pain
- bone deformities
- fractures
- markedly elev alk phos
Characteristic histological finding in Paget’s:
mosaic pattern of lamellar bone - jigsaw puzzle
“woven bone”
lytic and sclerotic
T/F: Woven bone is produced when osteoblasts produce osteoid rapidly, which is always abnormal.
false
occurs initially in all fetal bones, later replaced by lamellar bone; in adults woven bone occurs after fracture or in Paget’s
Pts w/Paget’s dz have inc risk for development of ______________, such as ___________ in the area of abn bone growth.
malignant neoplasms
osteosarcoma
Paget’s dz on x-ray:
cotton ball appearance - sclerotic bone with areas of lucency
T/F: Paget’s dz typically affects a single bone.
false
multiple bones - 85% of cases
first warning sign - bone pain, warmth
Rare inherited disorder whereby the bones harden and become more dense:
osteopetrosis - “stone bone”
Infection of the bone or bone marrow:
osteomyelitis
Osteomyelitis in children typically affects the ______ bones, whereas in adults the _______ and ______ are MC affected.
long bones
vertebrae and pelvis
Organism MC isolated from all forms of osteomyelitis:
Staph aureus
[in the vertebral bodies, 50:50 with TB, called Pott’s dz]
T/F: In osteomyelitis, mixed infections are rare.
false
“mixed infx are the rule, rather than the exception”
Term used to describe all of the skeletal changes of chronic renal dz:
renal osteodystrophy
Changes seen in renal osteodystrophy:
- inc osteoclast bone resorption
- delayed matrix mineralization (osteomalacia)
- osteosclerosis
- osteoporosis
Children with renal dystrophy are at risk of:
- rickets
* growth retardation
In chronic renal failure pts, the is significant interrelationship btw:
- inadequate kidney function
- 2° hyperparathyroidism
- altered vit D metabolism
Fractures are classified as ______ or ______ when the overlying tissue is intact, and _______ or _______ when the fracture site communicates with skin surface.
simple or closed
compound or open
A fracture is displaced when:
the ends of the bone at fracture site are not aligned.
A fracture is comminuted when:
the bone is splintered or crushed.
A pathologic fracture is when:
the break occurs in bone already altered by dz process
A stress fracture is:
a slowly developing fracture that follows a period of inc physical activity in which bone is subjected to repetitive loads (sports training, long distance running).
Imaging used to dx a stress fracture:
- plain film x-ray (poor view of aligned fractures)
- bone scan
- uses radioactive tracer via IV, taken up in areas of osteoblast and inflammatory activity (also for tumor, infx)
T/F: Bone is unique in its ability to repair itself.
True
bone can completely create new bone by reactivating processes that normally occur during embryogenesis
Solitary bone cysts are MC in ________, and are predominantly in the _______ ends of ______ bones.
young males - 1st or 2nd decade
distal ends of long bones (humerus, femur)
X-ray of solitary bone cyst reveals:
- smooth thin cortex
- usu symmetrical
- close to epiphysis
- diameter of bone mb inc
- cavity filled with clear or bloody fluid
- lacking specific microscopic features
Early tx of solitary bone cyst aims at:
More aggressive tx:
preventing pathologic fractures
scraping sides of cyst (curettage), inserting bone chips
T/F: Recurrence of solitary bone cysts is common.
false
vs. aneurysmal - 25% recurrence
Aneurysmal bone cysts are MC in ____________, and are MC in the ________ of _____ bones, and are also found in __________.
females - 2nd or 3rd decade (mb in children)
metaphysis
long
vertebrae
Aneurysmal bone cysts are (benign/malignant) lesions that are (locally/distantly) aggressive.
benign
locally
Gross pathology of aneurysmal bone cysts:
- distortion of bone
- less symmetrical shape
- honeycomb appearance on x-ray
- spongy appearance on cut surface
- variable size of cystic spaces, usu contain blood
T/F: The MC bone tumors are primary.
false
METASTATIC - by far
Benign, bone-forming neoplasm characterized by small area of neoplastic tissue surrounded by wide zone of mature, reactive bone:
osteoid osteoma
Common findings of osteoid osteoma:
- less than 2cm
- MC solitary
- multiple lesions seen in Gardner syndrome
Osteoid osteoma usu occurs in ______________.
Common presenting sx:
children and young adults
night pain w/localized tenderness
X-ray of osteoid osteoma shows:
- small, well-circumscribed lesion
- round or oval
- near cortex
- surrounded by densely sclerotic bone
- radio-luscent or radio-opaque aspects
Gross examination of osteoid osteoma:
- gritty
- cherry-red
- surrounded by dense sclerotic bone
MC primary malignant bone tumor:
osteosarcoma
Osteosarcomas may occur in all age groups, but 75% of pts are _____________.
younger than 20 y.o.
3rd MC malignancy in adolescents (after leukemia, lymphoma)
Osteosarcomas MC occur in the distal _______ or around the ______.
distal femur
around the knee
75%
10% present w/METS
X-ray findings of osteosarcoma:
- combo of bone destruction/formation
- rarely involves jt space
- soft tissue spicules of calcium
25% lytic / 35% sclerotic / 40% mixed
Classic osteosarcoma:
- aggressive, rapid growth
- high risk of local spread
- “skip” lesions
- soft tissue involvement possible
- common early pulmonary mets
Histopathology of osteosarcoma:
- atypical cells
- large nuclei
- small amt cytoplasm
- osteoid formation
Uncommon bone tumor usually found around the knee in either the distal femur and/ or the proximal tibia:
fibrosarcoma
tumor produces collagen matrix but does not produce osteoid or chondroid
T/F: Fibrosarcoma is a primary bone tumor.
true, but mb 1° or 2° to:
- Paget’s
- chronic osteomyelitis
- prior bone infarct
- prior irradiation for bone cancer
Characteristic histopathology of fibrosarcoma:
sheets of spindle-shaped cells
An aggressive tumor composed of oval tumor cells and multinucleated tumor cells, referred to as giant cells, which are uniformly distributed throughout the lesion:
Giant cell tumor (GCT)
usu tumor of adulthood (>20) - MC in 3rd decade
X-ray of GCT shows:
- destructive radiolucent lesion
- usu oval shaped
- centered in epiphysis
- cortical erosion / thinning
- expands bone contour w/o border or new bone or sclerosis
Histopathology of GCT:
lg multinucleate cells formed by fusion of several cells (50+ nuclei)
Malignant tumor of bone composed of small, rounded cells that are uniform in size and densely packed:
Ewing’s sarcoma
avg age - 13-14
Histopathology of Ewing’s sarcoma:
- uniform, densely-packed cells
- single round/oval nucleus
- indistinct cellular borders
- resemble lymphocytes
X-ray of Ewing’s sarcoma:
“moth eaten” destructive lesion
Malignant dz of plasma cells in the bone marrow, with monoclonal overgrowth of one clone of plasma cells:
multiple myeloma
pathological fractures common
X-ray of multiple myeloma:
lytic lesions
In adults, more than ___% of skeletal metastasis originate from cancers of the prostate, breast, kidney and lung.
75%
In children, bony metastasis MC originate from:
- neuroblastoma
- Wilm’s tumor
- bone tumor
- osteosarcoma
- Ewing sarcoma
Skeletal mets are typically (uni/multifocal).
multifocal
Nonsynovial joints are “solid”, in that:
they lack a joint space and provide for minimal movement.
Nonsynovial joints provide structural integrity.
pubic symphysis, cranial sutures
Synovial joints consist of:
two (or more) bone ends connected through a joint capsule of dense fibroconnective tissue.
joint may be strengthened by ligaments and muscles.
The articular surfaces of bone and cartilage are covered by a thin synovium capable of producing a clear fluid that acts as a __________ and provides nutrition for the _____________.
lubricant
articular hyaline cartilage
Hyaline cartilage is composed of:
type 2 collagen
water
proteoglycans
chondrocytes
Hyaline cartilage is a unique connective tissue ideally suited to serve as an:
elastic shock absorber and wear resistant surface
Dz that destroy articular cartilage do so by activating the ___________ and decreasing the production of ________, thereby accelerating the rate of matrix breakdown.
The chondrocytes react by increasing _____________ however, the response is usually inadequate.
catabolic enzymes
inhibitors
matrix production
Cytokines such as ____, _____, and _____ trigger the degradative process, and their sources include:
IL-1, IL-6 and TNF-alpha
- chondrocytes
- synoviocytes
- fibroblasts
- inflammatory cells
MC type of joint dz:
osteoarthritis
aka degenerative joint dz (DJD)
T/F: Osteoarthritis is characterized by the progressive erosion of articular cartilage.
true
considered to be an intrinsic disease of cartilage - biochemical and metabolic alterations result in breakdown
T/F: Secondary arthritis refers to arthritis due to the aging process and involves no other predisposing disease.
false
primary (idiopathic) arthritis
DJD damages are often irreversible because articular cartilage is:
avascular
aneural
alymphatic
When chondrocytes release IL-1, IL-6, and TNF-alpha, this inhibits synthesis of:
type 2 collagen
proteoglycans
X-ray of DJD shows:
- jt space narrowing
- marginal osteophyte formation
- subchondral bone cysts
- sclerosis
Nodes assoc w/DJD:
- Heberdon - DIPs
* Bouchard’s - PIPs
Histopathology of DJD:
- fibrous lined cysts in subchondral bone
* osteophytes
Chronic systemic inflammatory dz of unknown cause, characterized by polyarthritis which is often progressive and deforming:
rheumatoid arthritis
RA is MC assoc with rheumatoid factors, which are:
anti-IgG autoantibodies
[unclear; notes also say IgM, IgA]
RA jt involvement is typically (oligo/poly) articular, (unilateral/bilateral), and (a/symmetrical).
poly
bilateral
symmetrical
Commonly affected joints of RA:
- MCPs
- PIPs
- wrist
- elbow
- knee
- ankle
- MTPs
The primary joint lesion in RA occurs in the ___________ of affected joints and is called:
synovial membrane
diffuse proliferative and exudative synovitis
Histopathology of rheumatoid synovitis:
- multiple layers
- proliferative (hyperplastic) synoviocytes
- lymphocytic infiltration
In RA, deformity and dislocation of misshapen bone ends are caused by:
- muscular imbalance and contracture
* laxity of capsule and ligaments previously distended by effusion
The extra-articular manifestations of RA occur more often in sero(negative/positive) pts with (mild/severe) dz and circulating complexes of ___________.
positive
severe
rheumatoid factor
Describe rheumatoid nodules.
- subQ
- 20-25% of pts
- firm, nontender
- over bony prominence
- lungs, heart, eyes, tendon sheaths as well
Describe rheumatoid arteritis.
- inflammatory vascular lesions
- venules, capillaries, arterioles, arteries of skin/organs
- mb systemic necrotizing vasculitis of sm/med arteries
In RA, enlargement of regional lymph nodes is (un/common) and palpable splenomegaly occurs in __% of pts.
common
10%
Felty’s syndrome:
- RA
- splenomegaly
- leukopenia
Multiple factors and complex mechanisms are implicated in the pathogenesis of RA, among them:
- autoimmunity
- enzymatic
- increased cytokine activity
- other mechanisms of jt inflammation/destruction
- genetic predisposition
- environmental influences
80% of RA pts test positive for RF in ______ and _________.
serum
synovial fluid
(10-20% in JIA)
RF is not exclusively found in RA, but also tests positive in conditions such as:
- Sjogren’s
- SLE
- progressive systemic sclerosis
- infectious hepatitis / HCV
- PM/DM
- syphilis
- TB
Because RF is non-specific, new tests have been developed for RA, such as:
- anti-citrulinated protein antibodies (ACPAs or anti-CCP)
Chronic systemic polyarthritis of unknown etiology with onset at less than 16 years of age:
juvenile idiopathic arthritis (JIA)
aka JRA or Still’s dz
JIA and RA are similar, but differences of JIA include:
- high fever
- rash
- lymphadenopathy
- less jt pain
- less frequency of RF
- less subQ nodules
A group of diseases characterized by inflammatory arthritis and an assoc w/ HLA-B27 or triggering infx:
seronegative spondyloarthropathies
Examples of seronegative spondyloarthropathies include:
- reactive arthritis
- ankylosing spondylitis
- enteropathic arthritis
- psoriatic arthritis
Chronic inflammatory jt dz of the axial skeleton, esp SI jts:
ankylosing spondylitis (AS)
Associated complications: uveitis, aortitis, amyloidosis, ++
___% of AS pts are HLA-B27 positive.
90%
Progression of AS:
- HLA-B27 immunogenetic phenotype may predispose to development of autoantibodies directed at joints after infx
- chronic synovitis causes destruction of articular cartilage
- Inflammation of tendon/lig insertions leads to bony growths
Autoimmune rxn initiated by response to a prior infx, characterized by triad of arthritis, non-gonococcal urethritis or cervicitis, and conjunctivitis:
reactive arthritis (Reiter’s)
Reactive arthritis MC affects:
males in 20’s & 30’s
HLA-B27 + (80%)
Reactive arthritis is MC assoc with which GI and GU infx?
GI - salmonella, shigella, yersinia, campylobacter
GU - chlamydia
50% of reactive arthritis pts have waxing and waning sx that resolve in ____ to _______.
50% have recurrent _________, _________, and ______.
weeks to 6 months
arthritis, tendonitis, and LS back pain
Reactive arthritis MC affects which jts?
SI knees ankles feet toes fingers (sausage)
Enteropathic arthritis MC affects which jts?
knees and ankles
but also mb involve wrists/fingers/toes
Enteropathic arthritis refers to a non-reactive arthritis which occurs following _____ infx by ___________________, and usu occurs w/in (hours/days/weeks) of the initiating infx.
bowel
Salmonella, Shigella, Yersina, Campylobacter
days
Proposed mechanism of enteropathic arthritis:
ab response to LPS
THE ORGANISMS DO NOT INFECT JTS
T/F: Psoriatic arthritis describes the jt involvement assoc with psoriasis.
false
psoriatic arthritis is a distinct condition
5% of pts with psoriasis are affected
First jts usu affected by psoriatic arthritis:
DIP jts of fingers and toes
“sausage” appearance d/t tendon sheath inflammation
may become widespread - wrists, shoulders, ankles, knees, hips
20-40% develop SI and spinal dz
At what age does psoriatic arthritis usu develop?
35-45
Distinctive features of psoriatic arthritis:
- nail (fairy) pitting
- onycholysis
- histo and jt destruction similar to RA
- more frequent remissions than RA
Mechanisms of infectious (septic) arthritis infx:
- hematogenous spread
- trauma / foreign body
- adjacent infx (abscess, osteomyelitis)
Classic presentation of infectious arthritis:
sudden development of single acutely painful and swollen joint with restricted ROM
MC organisms in infectious arthritis:
- staph (MC in adults)
- strep (2nd MC)
- gonococcus (pathognomonic trunkal vessicles)
- H influenza (MC in kids except where vax)
- Salmonella (sickle cells pts)
- gm neg bacilli
- E coli (elderly, IV drug users, seriously ill)
- psuedomonas (kids w/puncture wound)
T/F: Pts with artificial jts are less likely to contract infectious arthritis, but sx and tx are the same.
false
more risk w/artificial jts
different organisms
different sx, tx
Organisms notable for being seen in spinal septic arthritis:
- M tuberculosis
- Salmonella spp
- Brucella spp
_________ arthritis is often “migratory” with multiple jts flaring up, and fever is less common.
Gonococcal
Misdiagnosis or delayed tx of infectious arthritis leads to:
joint destruction
dx by aspirating fluid (hospital)
T/F: Tuberculous arthritis is decreasing in incidence as TB is further eradicated.
false - increasing as TB reemerges as an important infx dz
Spread to jt usu from
- adjacent TB osteomyelitis
- hematogenous spread of pulmonary TB
The onset of jt involvement is usu slow / insidious
Jts MC affected by TB arthritis:
The involved joint often shows:
wt bearing jts
- hips (more)
- knees
- ankles (less)
- confluent granulomas
- central caseous necrosis
Tuberculosis of the spine (aka Pott’s dz) MC affects the (cervical/thoracic/lumbar) vertebrae and usu comprises both tuberculous ________________. The inflammatory and destructive processes involve ___________________, leading to (kyphotic/lordotic) angulation and cord compression.
thoracic and lumbar
osteomyelitis and arthritis
adjacent vertebral bodies and IV discs
kyphotic
Principle vector of Lyme dz:
deer tick, Ixodes scapularis
Spirochete infx that causes Lyme arthritis:
Borrelia burgdorferi
Dominant feature of late Lyme dz:
arthritis
tends to be remitting and migratory
MC jts involved in Lyme arthritis:
- knees
- ankles
- shoulders
- elbows
usu 1-2 jts affected
Characteristic rash of Lyme dz:
erythema migrans
Viral arthritis can result from numerous viruses, including:
- parvovirus B19
- rubella
- HCV
- HIV
The 2 MC crystalline arthritis conditions are:
- gout
* pseudogout
Gout is d/t jt space deposition of _____________ crystals whereas pseudogout is d/t deposition of ______________ crystals.
monosodium urate (uric acid)
calcium pyrophosphate
T/F: Increased uric acid levels lead to gout.
not necessarily
~10% of western hemisphere have hyperuricemia
less than 0.5% develop gout
The multifactorial development of gout includes:
- genetic predisposition
- increasing age
- lead toxicity
- lifestyle
- obesity
- heavy alcohol intake
- drugs
- aspirin
- thiazide diuretics
- loop diuretics
Hyperuricemia may develop d/t:
- inc uric acid production
* dec uric acid excretion
Term used for gout developing as a consequence of ingesting lead contaminated alcohol (moonshine):
saturnine gout
T/F: Synovial fluid is an efficient solvent for monosodium urate, which causes slow formation of crystals.
false
poor solvent! hyperuricemia leads to supersaturation leads to crystals precipitating out
Term used to describe the optical property assoc w/ certain transparent crystals in which the speed of propagation of light along the major and minor axes of the crystal differs, causing the plane of polarized light to be rotated:
birefringence
seen in gouty arthritis
When polarized filters are used in microscopy, the background appears (light/dark), and birefringent materials like _____ and ______ appear (brighter/darker).
dark
MSU and CPPD
brighter
Impact of crystals in jts:
- chemotactic to leukocytes
- activate complement
- macrophages phagocytose uric acid, release toxic free radicals and leukotrienes
- activated neutrophils release lysosomal enzymes
- deposition in kidney -> gouty nephropathy, mb renal failure
Pathognomonic lesion of gout:
tophus - masses of crystalline or amorphous urate deposits surrounded by an inflammatory reaction of macrophages, fibroblasts, and giant multi-nucleated cells.
Classic joint involvement of gout:
1st MTP jt
MC jts involved in pseudogout:
- knees
- ankles
ranges from asx/mild to significant jt damage
Bursitis is often assoc with:
* chronic trauma secondary to: * RA * gout * jt infx * calcification in/around bursa
Small (1-1.5 cm) cyst usu located near a jt capsule or tendon sheath:
ganglion cyst
common in wrist
usu pea-sized, firm, fluctuant
A ganglion arises as a result of:
cystic degeneration of CT
lacks a true cell lining
fluid similar to synovium
NO communication w/jt space
Herniation of synovial fluid through jt capsule may produce:
a synovial cyst
A synovial cyst in the popliteal fossa is called:
Baker’s cyst
common in RA (but not exclusive to)
Term to describe several closely related benign neoplasms that develop in the synovial linings of joints, tendon sheaths and bursae, characterized by inflammation and overgrowth of the jt lining:
villonodular synovitis
MC forms:
- pigmented (PVNS)
- giant cell tumor of tendon sheath (GCTTS)
MC jts assoc w/villonodular synovitis:
hip or knee
also affects shoulder, ankle, elbow, hand, foot
Histopathology of villonodular synovitis:
- mononuclear cell infiltrate
* hemosiderin-laden macrophages
MC jts affected by synovial sarcoma:
knee and ankle
close to jts, tendon sheath, bursa
Two basic types of skeletal muscle atrophy:
- disuse
- generalized (immobilization)
- localized (casting)
- neurogenic
T/F: A muscle cell and a muscle fiber are the same thing.
true
each cell contains hundreds to thousands of myofibrils
exercise causes increase of myofibrils (not cells)
____________ often occur in neurogenic atrophy as a result of opposing muscle groups encountering (reduced/increased) resistance.
Contractures
reduced
Term used to describe a broad range of inherited dz characterized by progressive muscle damage and weakness [over 100 different forms]:
muscular dystrophy
MC form of muscular dystrophy:
Duchenne’s
also one of the most serious
Duchenne’s is d/t a defective gene on (X, Y) chromosome, leading to inability to produce one of the proteins in the skeletal muscle cell membrane, ________, absence of which permits excess _______ to penetrate the sarcolemma (mm membrane).
X
dystrophin
calcium
Duchenne’s ago of onset is usu:
MC muscles affected first:
Survival time:
2-6 y.o. (often wheelchair-bound by 12)
pelvis, hips, upper arms and legs
rare beyond 20’s
How does excess calcium entry harm muscle cells?
causes the creation of more ROS than cell’s oxide-scavenging enzymes can process. Continued calcium entry causes further oxidative stress, ultimately resulting in cell death. They necrose and are replaced by fibrous CT or adipose (late).
Characteristic muscle biopsy of Duchenne’s:
- degen and atrophy of fibers
- some fiber regeneration
- hypertrophy of remaining fibers
- scattered inflammatory cells (early)
Duchenne’s is an (X, Y) linked (dominant, recessive) dz, occurring almost exclusively in (boys, girls).
X
recessive
boys
Neuromuscular dz leading to fluctuating muscle weakness and fatigability:
myasthenia gravis
In myasthenia gravis, weakness is usu caused by _________ that block _________ receptors at the post-synaptic neuromuscular junction, inhibiting the (stimulative, inhibitive) effect of the neurotransmitter.
circulating antibodies (present in 90%)
acetylcholine
stimulative
Risk factors for myasthenia gravis:
- female sex
- age 20-40
- familial Hx of MG
- presence of autoimmune dz
- D-penicillamine ingestion (drug-induced MG only)
The antibodies in MG are produced by _____ cells, that have been derived from __ cells.
plasma
B
The hallmark of myasthenia gravis is:
The MC first presenting symptom is:
muscle weakness that worsens during periods of activity and improves after periods of rest.
weakness of eye muscles
Which muscles are especially susceptible to MG:
Muscles that control eye and eyelid movement, facial expression, chewing, talking, and swallowing.
mb also neck and limb muscles, breathing muscles.
10% of pts with MG, esp older males, have ________, and most other pts have___________________.
thymomas
follicular hyperplasia of the thymus
MG can usu be controlled with meds, used for what 2 reasons:
What surgery may help?
- direct improvement of weakness
- reduction of autoimmune process
thymectomy (esp w/out thymoma)
T/F: MG is an insidious and progressive autoimmune condition.
false
sx may come and go, but don’t usu get worse as pt ages. For some, sx decrease after 3–5 years.
MC thymic abn in females?
MC in males?
- thymic hyperplasia - women
* thymoma (benign tumor) - men
The classic biopsy of MG shows:
- lg collections of lymphocytes
- necrotic muscle fibers
- pale
- atrophic
T/F: In the worst myasthenia crisis, paralysis of the heart occurs.
false - the respiratory muscles can be paralyzed, requiring assisted breathing
the heart is never affected by MG
Basis for MG diagnosis:
- Hx
- PE
- 2 positive dx tests
- serological (anti-ACHR abs)
- electrodiagnostic (nerve stim)
Syndrome that causes progressive muscle weakness, usually first noticed in the upper legs and upper arms:
Lambert-Eaton syndrome (LES)
mb good strength initial, and dec w/prolonged exertion
60% of cases of Lambert-Eaton are assoc with:
SCC (small cell lung cancer)
[syndrome dx may precede cancer detection]
In LES, abs directed against _________ calcium channels in the neuromuscular jct prevent normal function, which inhibits _____ release essential for normal muscle tone.
presynaptic
Ach
Dx of LES is by:
- chest x-ray - poss malignancy
- abs to calcium channels
- nerve conduction studies
A group of closely related, muscle-specific autoimmune diseases occuring as a result of immune mediated inflammation and vascular damage to striated muscle:
MC forms:
idiopathic inflammatory myopathies (IIM)
- dermatomyositis
- polymyositis
- inclusion body myositis
Definitive dx of IIM requires:
Other tests used to support dx:
muscle bx
- EMG
- MRI
Connective-tissue dz characterized by inflammation of skeletal muscle and skin:
dermatomyositis (DM)
The mechanism of injury in DM is:
complement-mediated damage to blood vessels in muscle and skin, with secondary atrophy and lymphocytic inflammation d/t ischemia.
The cause of DM is unknown, but mb:
- post-viral infection autoimmune reaction
* paraneoplastic syndrome
Although DM is primarily a dz of adults, it also is observed in children, usually aged ________.
5-14 years
Dx of DM is based on:
- Hx of muscle weakness
- skin involvement
- inc CPK, ESR
- abn EMG
- abn muscle bx
2 classic histopathology findings of DM:
- mixed B- and T-cell perivascular inflammatory infiltrate
- perifascicular muscle fiber atrophy
- invading inflammatory cells
- necrotic muscle fibers
- regenerating muscle fibers
A characteristic clinical finding of DM is:
periorbital heliotrope rash
- symmetric
- purple-red
- macular eruptions of eyelids and periorbital tissues
mb Gottron’s sign
- purple-red papular rash
- dorsal MCPs and IP jts
mb Shawl sign
- erythematous rash
- shoulders, delts, neck
- V sign - if on the ant neck
Pts with polymyositis (PM) usu present with:
- symmetric weakness
- proximal UEs and LEs
- neck flexors
- muscle pain / tenderness
- distal weakness (late)
A poor prognostic sign of PM seen in 1/3 is:
dysphagia secondary to oropharyngeal / esophageal involvement
T/F: PM has a bimodal onset, in adults and children 5-14.
false - that’s DM
PM is rare in under-20s
Histopathology of PM - early? late?
Early -
* pale enlarged muscle fibers
* macrophages surrounding w/some invasion
Late -
* complete muscle fiber invasion by macrophages
Muscle bx of PM classically shows ___ lymphocyte inflammation.
T8 lymphocytes
Inclusion body myositis (IBM) is characterized by:
slow, steadily-progressive weakness and wasting of the distal and proximal muscles, most apparent in the muscles of the arms and legs.
Muscle fiber bx of IBM is characterized by:
- focal areas of WBCs and other inflammatory cell
- deposits of amyloid-related proteins
- inclusions (buildup of abn proteins)
- vacuoles
Benign tumors of striated muscle that usu present as a round mass in the region of the neck (90%) are called:
rhabdomyomas
Characteristic histopathology of rhabdomyoma:
- well-differentiated lg cells that resemble striated muscle
- deeply eosinophilic
- polygonal
- small, peripheral nucleus
- occasional vacuoles
2 non-head and neck varieties of rhabdomyoma:
- genital (usu female, asx)
* cardiac (peds, hamartoma)
Malignancy that arises from embryonic mesenchymal cells with potential to develop into skeletal muscle and the MC soft tissue tumor in children:
Rhabdomyosarcoma
Rhabdomyosarcomas are MC dx’d in what body region:
- head and neck (ORBIT, face, scalp)
- GU system
but may occur anywhere
What are the 2 MC subtypes of rhabdomyosarcoma (of 5)?
- embryonal
- alveolar
- botryoid
- spindle cell
- anaplastic (undiff)
Histopathology of rhabdomyosarcoma:
- pleomorphic cells - various size, shape
- bundles of spindle-shaped cells
- elongated hyper-chromatic nuclei
- poorly differentiated / anaplastic
- mitotic figures
~90% of cases of rhabdomyosarcoma occur in pts under ____ years, with most cases occurring in the _____ decade.
25
1st decade
How many chemo txs does a myosarcoma pt need?
tumor
the end
