BS - Eye Muscle Disorders - Week 4 Flashcards
Name 2 types of EM disorder causes and give three causes for each type.
Neural causes
- abnormal control - brain centres
- bad neural connections - cranial nerve/pathways
Muscular/mechanical causes
- muscle insertions (tropia/phoria)
- orbital congestion
- muscle capacity
Give two examples of an inflammatory orbital congestion disorder.
Grave’s disease
Thyroid eye disease
Give two examples of neuromuscular junction disorders.
Myasthenia gravis
Myotonic dystrophy
Give an example of an inherited neuropathy affecting the EOM, and describe how its transmitted.
Lebers syndrome, a mitochondrial disorder.
What is the difference between thyroid eye disease and Graves disease (5)?
Graves disease is an endocrine disorder and the primary insult in in the thyroid. It may or may not express eye disease
Thyroid eye disease - primary insult in ocular, with normal thyroid function euthyroid.
Does Graves disease always cause eye disease?
No
What can be said of the inflammation grade of thyroid eye disease clinically (2)?
It is low grade, and might be early or preclinical Graves disease.
What is thyroid eye disease caused by?
Aberrant immune response
What is thyroid eye disease secondary to?
Hyperthyroidism
What does the hypothalamus sense, and what does it release in response?
Senses low T3/T4 in blood, and releases thyroid regulating hormone - TSH.
What does the anterior pituitary gland release, and what stimulates it?
TRH stimulates the APG to release thyroid stimulating hormone - TSH
What does the thyroid gland release, and what is it stimulated by?
Released thyroglobulin TGB, stimulated by TSH.
What happens to thyroglobulin?
Becomes T3/T4
What does T3/T4 do?
Gives feedback to the pituitary and hypothalamus.
Which is the only endocrine gland to store its own secretion, and what does it store?
Thyroid gland, storing TGB
Stimulation of which cells results in the production of TGB?
Follicular cells of the thyroid
What do parafollicular cells produce, and what does it do?
Calcitonin, inhibiting osteoclasts
What 7 actions does the thyroid have on the body?
Increases heart rate Increases glucose turnover Increases body temperature Increases Na+/K+-ATPase synthesis Increases protein synthesis Increases lipolysis Increases bone turnover
Describe the mechanism of Graves disease (5).
Antibodies (long standing thyroid stimulators) directed against thyrotropin receptors found on the endothelial surface of thyroid follicular cells, mimicing the action of TSH, but not subject to normal feedback.
Name two hypotheses for the cause of Graves disease.
Genetic tendency (lack of T-cell suppression)
or
Prior exposure to gut bacteria which have receptors on their cell membranes with homology to TSH-receptors, giving rise to antibodies agonistic to TSH-receptors, overstimulating them
The development of Graves disease requires the participation of which cell?
Self-reactive helper CD4+ T-cells, producing an antibody mediated autoimmune response
Name 5 ocular manifestations of Graves disease.
Lid retraction Lid lag Proptosis Extraocular muscle involvement Optic nerve dysfunction
What is the age of onset for Graves disease in men and women?
What is the risk for smokers?
Women - 20-40s
Med 50-60s
Smokers at 2x risk
Name some general systemic symptoms of Graves disease.
Anxiety, irritability, insomnia, irregular hear beat, fine tremor of hands/fingers, increased perspiration, heat sensitivity, weight loss but normal food intake, brittle hair, goitre, light to no menstruation, frequent bowel movements
Name two demopathies of graves disease.
Local swellings of feet and lower legs, altered colour and itch.
Name 4 histopathologies of thyroid eye disease.
Increased orbital fat content
EOM swelling
Increased fibrosis and GAG synthesis - swelling pressure
Inflammatory cell infiltration of the EOM - muscular fibrosis
List the clinical expression types of thyroid eye disease, and percentage for each.
80% hyperthyroid
20% euthyroid
What kind of disease is myasthenia gravis, what is affected, and how?
Autoimmune disorder causing weakness of skeletal muscles due to antibodies formed against nicotinic receptors
List three ocular manifestations of myasthenia gravis.
Ptosis
Diplopia (often vertical)
Fatigue on repeated effort (+10x)
Briefly describe the neuromuscular junction mechanisms.
Ach released from the nerve terminal following the action potential.
Move across the synaptic cleft to Ach receptors on the post-synaptic membrane.
Ach-esterase on the post-synaptic cleft scavenges and hydrolyses unbound Ach.
Describe the role of IgG in myasthenia gravis (3), and what happens in advanced cases (4).
IgG is an agonist of nAChR, and binds at the neuromuscular junction, blocking receptor activation of Ach.
Advanced - complement C9 colocalises with IgG on nAchR, internalising, disrupting and destroying nAchRs.
What population is most affected by myasthenia gravis?
Young women and older men
What is myasthenic crisis?
Complete loss of breathing capacity
Does thyroid/thymus dysfunction occur in those with myasthenia gravis?
Yes, in 5-15%.
Describe the action and purpose of tensilon/edrophorium chloride testing.
A short acting Ach-esterase that prolongs Ach action.
Intravenous gives transient improvement to muscle strength.
Clinically, improvement to ptosis.
Describe the single fibre electromyography test, and what it is for.
For testing myasthenia gravis.
Concentric needle electrode is inserted into the muscle to allow identification of action potentials from individual muscle fibres.
Jitter is seen in 95-995 of patients with myasthenia gravis.
Describe myotonic dystrophy, and how it is genetically transmitted.
Autosomal dominant condition that leads to myotonia - the inability to relax muscles.
Genetically, myotonic dystrophy is similar to what other disease?
Huntington disease.
What is the onset of myotonic dystrophy, and death?
Onset - 20-30s
Death - by 50s
Do individuals with myotonic dystrophy experience endocrine dysfunction?
Yes, its common due to epithelial dystrophy, especially testicular, leading to baldness.
List 7 ocular manifestations of myotonic dystrophy.
Ptosis Fatigue Cataracts Pigment epithelial dystrophy Retinal degeneration Ciliary body dysfunction Reduced IOP
