1. cells

2. fibers

3. ECM

An autsomal dominant disorder that causes organ abnormalities.

Cardiovascular: aorta issues --> dissecting anneurysm,stenosis, angina, CHF, MVP

Skeletal: tall, long limbs, arachnodactyly, long skull

Can also see pectus excavatum (depression in chest), weak ligs, tendons, jt capsules, hyperflexibility (can cause dislocations

Dilocation of the lens

sever myopia due to elongation of the eye (near-sightedness)

Retinal detachment

A group of autosomal dominant inherited disorders of connective tissue.

Results in hyperelasticity and fragility of the skin

(also joint hypermobility)

Bleeding diathesis

--> EDS VI is spontaneous rupture of large arteries, bowel, and uterus (sometimes the aorta)

can lead to death in 3rd or 4th decade

Skeletal: severe kyphoscoliosis

Visual: blindness from retinal hemorrhage, bladder rupture

What is another name for neurofibramatosis 1 (NF1)?

describe it

von Recklinghausen disease

Affects 1 in 3500 people (one of the most common autosomal dominant disorders)

- Disfiguring neurofibromas

- Cafe-au-lait spots (usually 6 or more spots)

- Pigmented lesion of iris (Lisch Nodules)

What skeletal lesions can result from NF1?

are there any other outcomes?

1. Malformation of the sphenoid bone

2. Thinning of cortex and long bones

- Bowing and pseudoarthrosis of tibia

- bone cysts

- scoliosis

3.  Other outcomes --> mild mental impairment

Leukemia in children is more likely

1. bilateral 8th cranial nerve tumors (acoustic neuromas)

2. Meningiomas

3. gliomas

What are three features of mixed connective tissue diasease (MCTD)?

Treatment?

Who is affected most?

1. SLE (butterfly rash, Raynauds, Arthralgias)

2. Systemic sclerosis (scleroderma) - swollen hands, pulmonary fibrosis, esophageal hypomobility

3. Dermatomyositis or polymyositis - proximal mm weakness with or w/o mm soreness

Treatment: corticosteroids are helpful

80-90% are women, avg age of 37

What are three common organs that MCTD affects?

what other systems in the body can it affect?

lung

heart

kidneys

Lymph system (lymphadenopathy)

GI disorders

It is an autoimmune disease that results in arthritis plus moisture-producing gland impairments

Usually a sign of MCTD

- peripheral neuropathies

- aseptic meningitis

- cerebral infarct/hemorrhage

- trigeminal sensory neuropathy

Women are twice as likely to get it

Most are age 50 and above, with most of them being 70 or older

Suden onset of soreness/stiffness

diffuse pain and stiffness in shoulder and pelvic girdles

subacromial, subdeltoid, ilioperitoneal bursitis; hip synovitis

Difficulty with ADL and IADL for no identifiable reason.

(rolling in bed, trouble standing up or going up stairs, trouble with dressing due to shoulder pain)

The pain may start unilateral and progresses to bilateral and symmetric

Joint synovitis especially wrists and MCP joints

Diffuse distal extremity edema

CTS

Tenosynovitis

Rapid response to prednisone within one week (many people stop taking full dose because they feel better)

There is a 30 percent recurrence rate

Prednisone cautions:  weight gain, mood swings, cataracts/glaucoma, DM, easy bruising, Cushing;s syndrome, osteoporosis particularyly od spine and femoral head (Fx risk)

Risk: stroke!

Treatment for bursitis - led meds do their job, possibly stay away from heat

Marked by local or regional pain syndrome (trigger points - hyperirritable foci in tuat skeletal mm, thought to be a contracture w.i the muscle)

Can palpale the TrP - can be local or referred pain

Active - pain at rest or with activity of specific muscle

Latent - no pain but there is restricted mov't and/or weakness of muscle

Satellite - one that can develop in a different part of the muscle or in different mm within the referred pain pattern

1. sudden overload or overstretching

2. direct impact

3. posture

4. psychologic stress

5. repetetive physical stress

6. structural abnormalities

7. overwork fatigue

8. radiculopathy

9. indirect activation (other trigger points, visceral disease)

Dysfunctional motor end plates

-greater spontaneous EMG activity

- sensitized nociceptors associated with dysfunctional mtor end plates

 This causes sensitization in the spinal cord, which leads to nociceptors sensing pain, going to CNS

Irradiation to other dorsal horn cells --> referred pain

Trauma --> release of excessive Ca++ --> leads to sustained contraction --> leads to decreased blood flow --> leads to ischemia

This all leads to decreased ATP production, and anerobic metabolism (gross of 4 ATP, net of 2 ATP)

Hallmark of MFS: palpabl, taut, painful band w/i a mm with characteristic and reproducible referred pain in response to sustained pressure

(rope, crackle, gristles)

TrP are self-sustaining and self-perpetuating

Also see: jump sign, local twitch response, and numbness and paresthesia

Injection (dry needling, saline, local anesthetic)

Ice, ultrasounds, sustained pressure

Spray and stretch (fluorimethane)

Post-isometric stretch

MFS - single or multiple, may cause referred pain, taut band, local twitch response

FMS - multiple sites, symmetrical, do not cause referred pain, but often cause a total body increase in snesitivity

Perimysium - surrounds fascicles

Epimysium - surrounds muscle body

Endomysium - surrounds muscle fiber

inactivity

ischemia

malnutrition

aging

chronic disease

denervation

corticosteroid inducted myopathy

1. Myophagocytosis

2. satellite cells become myoblasts and repair the injury

In chronic disorders, the muscle fiber necrosis wins out over regeneration, which can lead to fibrosis, and have functional implications, such as loss of contractility and extensibility/elasticity

Lysis of muscle cells (focal nercrosis) secondary to:

-HT

-viruses

-Anesthesia

-ETOH

Myoglbin is released into circulation, filtered thru kidney, and may develop ARF.  Will result in myoglobulinuria (port wine urine)

Inflammation of the muscle can occur in response to muscle necrosis or a hypersensitivity reaction - lymphocytes infiltrate the muscle and damage it.

The patient will present with symmetrical proximal muscle weakness and presence of inflammatory cells (SED rate)

What is the function of bone? 

Mechanical:

- protection of organs

- limb support

-high tensile strength

Mineral storage (Ca, Ph, Na, Mg) 

Hemopoietic

1. Osteoprogenitor: arise from stem cells and are in the bone marrow (They give rise to osteoblasts)

2. Osteoblasts: produce and mineralize bone

3. Osteocytes: an osteoblast that is completely embedded in the bone matrix ina lacuna; responsible for detecting and responding to mechanical forces

4. Osteoclasts: bone resorption (in the macrophage family); only reabsorbs mineralized bone

Cortical bone is dense, compact, and makes up the shell that defines the shape of the bone.

It makes up 80 percent of the adult skeleton (most diaphyses and around cancellous bone at the end of joints)

Its main function is biomechanical

The basic unit of cortical bone is an osteon

Basic unit of cortical bone.

Made up of Haversian canals and the osseous lamellar bone around it.

It is a cylinder composed of 4-20 concentric lamellae arranged arpund a central opening

Coarse, cancellous, spongy bone, usually found at ends of long bones within the medullary canal (can also be found in vertebrae and flat bones)

Contains many more bone cells than cortical bone

Can be found in femoral head and in the condyles

Highly organized and strong tissue

-Found in cortical bone

-Parallel arrangement of type I collagen fibers

Note: anything other than lamellar bone in adult skeleton is abnormal

Also, this type of bone is slowly manufactured

Irregular arrangement of type I collagen

- Numerous osteocytes in the matrix

-Haphazardly arranged collagen with low tensile strength (really just a scaffolding)

-Rapidly produced

-Found in fetus, areas surrounding a tumor, and infections and healing fractures

-Always pathologic in the adult skeleton

It is a mineral component which gives bone its hardness.

It is chiefly a form of calcium phosphate, and it is called hydroxyapatite

Nutrient arteries: supply marrow and internal 1/3 of the cortex

Perforating arteries: Arise from periosteal arteries; they anastamose in the cortex with branches from the nutrient arteries

Haversian canals: run parallel to the long axis of the bone; contain 1-2 blood vessels, lymphatics, and nerves

Volkmann's canals: run perpendicular to the long axis, connect to the Haversian canals, and carry blood vessels

1. cartilage proliferation

2. calcification of cartilage and then degeneration

3. bone formation on the cartilage remnants

4. resorption of bony trabecular tips

Bone is laid down in regular fashion at periosteal surface of diaphysis by osetogenic cells

Appositional growth (growth at the periphery)

COncurrent resorption of bone on inner, endosteal surface

-osteoporosis

- low BMI

- age

- poor nutrition

- "inactivity"

- metastasis

1. Inflammation (first week)

- Hematoma formation (sets up fibrin meshwork)

- extemsive necrosis (WBC, macrophages start to clean up debris)

- Neovascularization begins to occur peripheral to clot

- Early woven bone is laid down after 7 days

2. Reparative(1 weeks to months

3. Remodeling (months to 2-3 years)

- can only begin if there is approximation of the fracture ends by the callus bridge

- soft callus becomes hard and the cortex is restored

- lamellar bone replaces woven bone

Pulmonary embolism --> SOB

COmpartment syndrome (skin changes, motor loss, buring or paresthesias, diminished reflexes)

Fat embolism (femur bone marrow is very fatty)

Heterotopic ossification

Post-traumatic arthritis

Complex regional pain syndrome

Kids--> 4-6 weeks

Adolescents--> 6-8 weeks

Adults--> 10-18 weeks

- delayed union or non-union

- pseudoarthrosis

- avascular necrosis

- disease

- NSAIDS

-heterotrophic ossification

myositis ossificans

Abromal proliferation of bone (around the Fx site)

This can also occur in muscle (myositis ossificans)

- extraosseous non-new growth in bone

Inflammation of bone caused by infection (usually bacterial)

It needs a prtal of entry.

CHildren, elederly, anyone immunosuppressed, IV drug users are succeptible

Exongenous: more common in US; arrives via penetrating wounds, surgey, Fx, and external bacteria

Hematogenous: due to bloodborne organisms; more common in boys; see boils, impetego; can arise from any infection

Sheath of new bone formed beneath elevated periosteum

(surrounds sequestrum)

Delayed diagnosis --> cancellous bone is insensate, so onced the infection has spread to periosteum, there will be pain, swelling

Septicemia (bacteria in the blood (bacteremia) that often occurs with severe infections.)

Can also see Acute bacterial arthritis

A disorder of the ossification center in growing kids

- occurs at the epiphysis; the problem is bone necrosis

This is also referred to as: epiphysitis, osteochondritis, aseptic necrosis, avascular necrosis

- Most common osteochrodroses

- Idiopathic avascualr necrosis of capital femoral epiphysis of femoral head

- Bilateral in 10- 25 %

- 5:1 ratio for boys

- primaritly caucasians

- The healing stage can last from 1-3 years

1. Avascular: (quiet) last 1-2 weeks

- vascular interruption of the epiphysis --> necrosis of epiphysis (rest of bone is OK)

- can see capsulitis --> edema

2.  Revascularitzation (Fragmentation) can last 6-12 mos.

- new blood supply --> resorption of new bone deposits

- pressure deformity in weakened areas

- femoral head epiphyseal necrosis

- demineralization and revascularization

3. Reparative (2-3 years)

- new bone replaces necrotic bone

- femoral neck is short and wide due to collapse of femoral head (subluxation and Fx risk)

4. Regenerative (final mos.)

- gradual remodeling of the femoral head and neck - more likely in children

- may have residual deformity: older children --> can lead to OA

- Insidious onset

- Complaints about pain in groin, thigh, knee

(follows obturator nerve; specific tenderness over the hip jt. capsule)

- antalgic gait while running/walking

- symptoms worse w/ activity

- progressive loss of range of motion (IR and ABduction)

- sometimes leg length discrepency

Slipped capital femoral epiphysis (SCFE)

Posterior and inferior slippage of proximal femoral epiphysis on the metaphysis (femoral neck)

- up to 40% of cases are bilateral

Happens during the early adolescent growth spurt

Most common hip pathology in (obese) adolescents

- Boys>girls

- Black and Polynesian

- May or may not be associated with trauma

- Intermittent limp w/ antalgic gait

- Leg length discrepency and atrophy

- Poorly localized pain (usually referred to thigh, knee, groin)

- Loss of hip flexion, IR, and ABduction

Osteochondrosis of patellar tendon and tibial tuberosity

Most common in active boys 10-15 yrs (3:1 ratio)

Girls 8-13 yrs)

Timing: before epiphyseal plate is closed

- indirect trauma from quad contraction or repetitive knee flexion wth tight quads

- worse with tibial torsion and bone growth traction

- vascualr deficiency

- There is a strong tendon attached to "pre-bone"

- constant pain below patella

- swelling at tibial tubercle (tenderness)

-  heat

- muscle tightness: hamstrings, IT band, triceps surae, quad

2-3 weeks to 2-3 months of avoiding activities that cause pain (allows time for revascularization, fracture healing, and ossification)

NSAIDs and ICE

Bracing

Stretching

What is another name for osteonecrosis of the femoral head?

Osteonecrosis is necrosis of bone and bone marrow due to loss of perfusion

- ETOH use

- obesity

- pregnancy

- pancreatitis

- medications

-- oral contraceptive and also corticosteroids

Atrophy (inactivity, ischemia, age, disease, denervation)

Hypertrophy (increase deman --> increase metabollicaly active tissue)

Necrosis (myopathies from external toxins or internal structural disturbance)

1. myophagocytosis

2. satellite cells become myoblasts and reapair the injury

Lysis of muscle cell

Focal necrosis secondary to:

- hyperexertion

- viruses like influenze

- mild exercise (abnormal and a sign of an underlying metabolic disorder)

- anesthesia: halothane

- ETOH

Dissolution of skeletal muscle fibers

- release of myoglobin into the circulation

(myoglobulinuria - port wine urine; also acute renal failure)

Muscles are swollen, tender, weak (if acute) and there is cmore creatine kinase than usual on the hematologic workup

Rhabdomyolysis (lysis of muscle cells)

Inflammation (myositis - lymphocytes infiltrate muscle and destroy it; mm weakness)

Fibrosis - happens when degeneration gets ahead of regeneration; fibrotic tissue lacks strength and distensibility

1. Neurogenic muscle atrophy (denervation)

2. Myopathy or primary muscle disease (dystrophies, congenital myopathies, inflammatory myopathies, toxic or metabolic myopathies

3. Diseases of the neuromuscular junction

-myasthenia gravis

- Lambert-eaton syndrome

1. LMN disease (of the CNS)

- Spinal cord injury

- Anterior horn cell disease

-ALS

-poliomyelitis

-spinal mm atrophy

2. PNS

- ischemic neuropathies

- DM

-ETOH neuropathies

- uremia neuropathies

Neurogenic atrophy is a denervation atrophy secondary to loss of myofibrils and myofilaments (tends to affect distal musculature)

Reinnervation attempts with every episode of denervation

- adjacent motor units develop new axonal sprouts trying to "plug back in"

- results in giant motor neurons: cell bodies enlarge to support the larger motor unit

SMA refers to degeneration of the AHC (it is the 2nd most common lethal, autosomal recessive disorder after CF)

Type I: Werding-Hoffman (infantile SMA)

- progressive and severe weakness in early infancy (degeneration can begin in utero after motor units have been established)

Type III: Kugelberg-Welander (Juvenile SMA)

- Later onset and not necessarily progressive

- Used to be called limb-girdle MD

Non-inherited: spontaneous (30% of cases)

Inherited: Duchenne's --> most common non-inflammatory myopathy in children

- Severe, progressive x-linked degeneration of skeletal mm

(mother is carrier, affects primarily boys, progressive wasting of shoulder and pelvic girdle)

High levels of CK-MM found

Mutation of the gene coded for dystrophin

- A protein located on the inner surface of the sarcolemma

-- it links the cystoskeleton to the plasma membrane

--w/o it, muscle cells cannot regulate the influx of Ca++ --> this causes disintegration, wasting and weakness

This all leads to relentless degeneration of muscle fibers.  The degeneration outpaces regeneration, whihc leads to a progressive decrease in number of muscle fibers. There is myophagocytosis, but no inflammatory reaction.  A progressive increase in fibrofatty connective tissue can also be seen.

- elevated CK-MM from birth

-pelvic/shoulder girdle weakness

- muscular weakness is usually deteced in 3rd or 4th year

- pseudohypertrophy of calf muscles (fibrofatty connective tissue)

-contractures

-Gower's Sign

-          Gower’s sign (weakness of low back/hip extensor mm)

-          Difficulty standing up, use a wide BOS and then push up off legs with hands and crawl up to a standing position.  Usually go into a hip hyper-extension to compensate

Myotonic dystrophy is the most common form of adult dystrophy.

It is an inherited autosomal dominant disorder characterized by slow muscle relaxation

Clinical presentations include sustained muscle contraction and rigity (myotonia) and progressive weakness and wasting

lType I atrophy and type II hypertrophy

-          Type I – postural, oxidative, slow twitch, fatigue-resistant

-          Type II – distal mm, fast twitch

Far less necrosis and regeneration than seen in Duchenne's MD

Adult: onset between 20-30 yrs; progressive mm weakness and stiffness of distal limbs; facial and jaw muscles affected; cataracts; cardiomyopathy; DM; testicular atrophy; may have smooth muscle involvement

Congenital: seen only in offspring of women who have the symptoms of myotonic dystrophy.  INfants are born with severe muscular weakness, and there is a high incidence of mental retardation

Becker - 5 in 100,000

Duchenne - 20-30 in 100,000 live births

Mom in the carrier

Remember, both involve a problem with dystophin - the protein that connects the cytoskeleton of a muscle fiber to the surrounding ECM thru the cell membrane

Note: Becker's is somewhat like Duchenne's, but with less muscle necrosis

Becker's resembles Duchenne, but is slower in progression.  Those affected have a long life expectancy (compared with DMD, where life expectancy is around 20 yrs)

Those affected stay ambulatory for a long time --> toe walkers (true calf hypertrophy)

Tends to involve proximal musculature

Characteristics:

- muscle cramps

- scoliosis

- contractures

Genetic defect - not exactly sure what problem really is

Clinical presentation:

-mild form of MD --> starts with weakness and atrophy of facialm muscles and shoulder girdle

- lower extremity weakness is delayed

Typically don't get contractures, skeletal deformities, and hypertrophy