Musculoskeletal Flashcards
What musculoskeletal diseases are caused by autoimmune?
- Sclerodema
- Lupus
- Myasthenia gravis
- myasthenic syndrome
- rhumatoid arthritis
- anklylosing spondylitis
What are genetic musculoskeletal disease?
- Muscular dystophy
- marfan’s syndrome
- achondroplasia
What is scleroderma
- autoimmune disease
- numerous antibodies (ANA, anticentromere, scl 70 …)
- unknown trigger
- occurs primarilyin middle-aged (35-50) women (>4:1)
- all autoimmune diseases tend to afflict women more than men because autoimmune diseases begin during hormonal changes
- initially damages small blood vessels which leads to tissue ischemia and fibrosis
- BIG problem is blood vessel effects
- Excessive produciton of collagen (fibrosis) that affects
- skin
- GI tract
- lungs
- kidneys
What are scleroderma symptoms on the hands?
- Calcium deposits
- tissue dies and attracts calcium from blood
- looks like chalk
- tissue dies and attracts calcium from blood
- puffy fingers
- raynauds
- same physiology as cold day, but happens at much higher tempa nd shuts off blood completely
- digital ulcers and scars (from raynaud’s and cut off of circulation)
What is CREST?
“limited scleroderma”
- Calcinosis
- Raynaud’s phenomenon
- esophageal dysfunction- acid reflux and decrease in motility of esophagus
- sclerodactyly- thickening and thighteningof skin on the fingers and hands
- telangiectasia- dilation of capillaries causing red marks on skin surface
What is diffuse scleroderma?
How does it affect heart, lung, kidney, GI tract, joints?
- LUng fibrosis- leading cause of death from scleroderma
- decrease in diffusion
- decrease in compliance
- pulmonary arterial hypertension- PAH (very common)
- RV failure
- Heart
- cor pulmonale–> right heart failure
- fibrosis–> left heart failure
- pericarditis
- Kidney<– few will die from kidney failure d/t HD
- basement memebrane fibrosis–> decreased GFR, proteinuria (slow)
- Scleroderma renal crisis–> rapid onset renovascular disease (rapid)
- GI tract
- hypomotility, malabsorption
- Large joint contractures
- loss of joint mobility (including mouth/jaw)
- pain and fatigue
What is systemic lupus erythematosus?
- Autoimmune disease- type III hypersensitivity
- ANA (anti-nuclear antibodies)- also found in other autoimmune diseases
- unknown trigger
- Occurs primarily in young (15-30) women (>5:1), black and hispanics more than whites
- immune complexes damage blood vessels leading to vasculitis
- blood vessel damage can affect any organ- symptoms vary widely from patient to patient
- kidney is generally the most affected organ
- however, with HD, not likely to die from it
- CV disease is now the biggest problem and cause of death
- kidney is generally the most affected organ
Are lungs highly affected in lupus?
NO, generally cv disease is leading cause of death
What is Duchenne muscular dystrophy?
- x-linked genetic disorder that affects dystrophin, dystrobrevin or dystroglycans
- dystrophin links actin in muscle to sarcolemma to the basal lamina and evens tension through entire muscle fiber
- without dystrophin, we cannot evenly distribute tension throughout entire muscle fiber and when muscle contracts, it tears.
What tends to be around muscle cells of someone with muscular dystrophy?
- neutrophils because the muscle cell is damaged and your body sees need for repair
- muscles will not adapt and get stronger like normal because there is still no dystrophin
- also have variation in fiber size, degerating and regernerating fibers, immune cell infiltrationa nd increased fibrosis
What is myasthenia gravis?
- Antibodies bind to acetylcholine receptors and prevent them from working (IgG mediated)
- the more muscles are used throughout the day, the weaker the muscle gets because less and less acetylcholine vesicles are available
- now, less acetylcholine released and very few ach receptors are available, so more weakness occurs throughout the day
What is myasthenic syndrome?
- IgG antibodies attacking presynaptic VG calcium channel
- Therefore, acetylcholine is never triggered to be released into cleft
- no change in muscle strength throughout the day
- acetylcholinesterase inhibitor does not have any effect on patient.
- Receptor plentiful but not enough Ach in cleft (not even released to begin with)
Review of process for activation of neuromuscular junction (NMJ)
- Pre-synaptic voltage gated calcium channel allows Ca to come into presynpatic terminal
- signals acetylcholine vesicles to be released into cleft
- Acetylcholine diffuses, binds to acetycholine-gated cation channel
- cell depolarizes and voltage gated Na channel opens, allowing Na to enter cell, further depolarizing cell
- then voltage gated Ca channel opens, simultaneously opening gated Ca release channel on sarcoplasmic reicticulum
- Ca released into cell, causing actin/myosin formation and cell contraction
What is effect of myastehnia gravis on NMJ?
Blocked ACh receptors
What is effect curare at NMJ?
Drug that blocks ACh receptors temporarily and paralyzes muscle
What is effect of clostridium botulinum at NMJ?
- Neurotransmitter vesicles cannot fuse to the presynaptic plasma membrane to be released into the cleft
- long 1/2 life
What is effect of clostridium tetani at NMJ?
- Excessive neurotransmitter release into synaptic cleft
- permanently contracts muscle
What do undifferentiated mesenchymal cells differentiate into?
- Fibroblasts
- Cohrodroblast
- Osteoblasts
- Also (not covered)
- smooth muscle cells
- endothelial cells
- mesothelial cells
- adipocyte
What do chondroblast turn into? What do they release?
- Chondroblasts become chondrocytes
- chondrocytes make cartilage
What do fibroblasts release?
Collagen in cartilage and tendon, ligamnets
What do osteblasts differentiate to? What to osteoblasts make?
- Osteoblasts make bone
- also differentiate into osteocytes
What are osteoclasts?
Synctium of macrophages that eat bone
what is a diaphysis? epiphysis?
Diaphysis= long part of bone
epiphysis= ends of bone
What is an osteon?
Concentric ring of bones
Kyphosis? Lordosis? Scoliosis?
- Kyphosis- upper spine
- Lordosis- lower spin
- Scoliosis- s-curve, also affects lung
What is marfan’s syndrome?
- Autosomal dominant genetic disorder
- mutation in FBN1 gene which encodes fibrillin-1
- fibrillin-1 is esential for proper formation of elastic fibers
- Male and females equally affected, all racial and ethnic groups equally affected
What are symptoms of marfan’s?
- Skeletal system- most obvious symptoms
- above-average height, disproportionately long limbs with long fingers and toes
- abnormal curvature of spine- scoliosis, lordosis
- abnormal indentation (pectus excavatum) or protrusion (pectus carinatum) or sternum
- various minor skeletal malformations
- CV systme- most serious affects and leading cause of premature death
- regurg of mitral or aortic valves
- dilated aorta or an aortic aneurysm
- Lungs- pulmonary symptoms not a major feature of marfan
- spontanous pneumothorax is common
- Eyes- lens dislocation, vision problems
- Nervous system
- dural ectasia, weakeneing of connective tissue of dural sac encasing the spinal cord
What is achondroplasia?
- Autosomal dominant genetic disorder
- also 80% spontaneous mutation
- Mutation is in FGFR3 gene which encodes fibroblast growth factor recptor 3
- FGR3 is a negative regulator of bone growth
- the mutated form of the receptor is constitutively (always) active
- Male and female equally affected, all racial and ethnic groups- equally affected
What are skeletal system effets of achondroplasia?
- Tubular bones are short and thick
- skull is large, with a narrow foramen magnum, relatively small skull base
- congenitally narrowed spinal canal
- cervical kyphosis
What is cortical bone? Trabecular bone?
Cortical bone= compact bone
Trabecular bone= spongy bone
What is osteoporosis?
Loss of cortical and trabecular bone
- affects women more than men. Why?
- women start out with smaller bones to start with, make less bone overtime, and lose bone at a more rapid rate than men. also, women live longer
What happens to a osteoporotic vertebral body?
- Shortened by compression fractures (from loss of trabeculae bone)
- crush fracture in vertebrae typically does not cause spinal cord injury, but instead causes spinal stenosis
- can be painful/debilitating but no damage to spinal cord
What is osteoarthritis?
noninflammatory join disease
- Due to lifelong use of joints. Causes:
- traumatic injury
- dislocations
- sprains
- start wearing down cartilage layer and can cause bone to rub on bone
- 1/2 life of cartilage in acetablum is about 100 years. slowest turnover of any protein in the body
What are some inflammatory joint diseases?
Rheumatoid arhtritis
Anklyosing spondylitis
What are sites commonly affected by osteoarthritis?
- Hips
- knees
- lower lumbar vertebrae
- cervical vertebrae
- proximal and distal interphalangeal joints
- first tarsometatarsal joints
- (weight bearing sites)
What is characteristic for rehumatoid arthritis in hands?
- Swelling from chronic synotivits of metacarpophalangeal joints
- marked ulnar drift
- caused by chewing away of end of bones by immune response
- subcutaneous nodules
- subluxation of metacarpophalangeal joints with extension of proximal interphalangeal joints
- flexion of distal joints
How does OA and RA affect bone differently?
- OA affects head of affected bones
- RA affects entire bone length, including joint
- no good treatment
What is anklylosing spondylitis?
- autoimmune disease
- antibody for AS has not been identified
- men get AS more than women- unusual among autoimmune dx
- >90% of people with AS express HLA-B27 gene
- HLA-B27 near artic reation 24% sweden, 40% alaskan
- 0% south of equator
- 8% europ, 4% china, 6% usa
- affects entire body
- fusion of neighboring vertebrae- most sig. effect
- weight loss, fatigue, fever
- aortic regurgitation, bundle branch block
What is term for bone growth after puberty?
apposition- bone gets wider instead of longer
