Neurological Diseases: Module 2.10 - 2.11 Flashcards
What was the first chemical synapse to be discovered in detail?
Synapse at the neuromuscular junction.
Most studied synaptic connection.
Who won the Nobel Prize for the discovery of mechanisms at the neuromuscular junction?
Sir Bernard Katz
How many synapses occur between the motor neuron and the target tissue?
1 Synapse
Describe all the structural components of the neuromuscular junction.
* End Plate: Specializeed synapses between mtor neurons and skeletal muscle.
- Motor Unit: Group of muscle fibers innervated by the axon from one motor neuron.
- NMJ: Single point of synaptic contact between axon and muscle fiber.
- Post Junctional Folds: Invagination of Postsynaptic membrane. Greatly increase surface areas. Very high density of nicotinic Ach recptors.
- Active Zone: Regions in which vesicles fuse with presynaptic membrane and release ACh.
- Basal Lamina: contains proteins that mediate adhesion, including AChE, which hydrolyzes ACh to choline and acetate.
Where are the N type Pre-synaptic Calcium channels in relation to the postsynaptic receptors?
Aligned exactly opposite.
What causes the sharp local rise of calcium in the presynaptic terminal and not further in the neuron?
Ca ions do not diffuse long sdistances from their site of entry because free Ca is rapidly buffered by Ca binding proteins.
Acetylcholine receptors in the vertebrate neuromuscular junction are concentrated at the ____ of the junction folds.
Acetylcholine receptors in the vertebrate neuromuscular junction are concentrated at the top 1/3 of the junction folds.
How does the activation of Ach channels at the top of the junctional folds result in a action potential further in the muscle?
ACh depolarization allows opening of voltage gated Na channels at the bottom of the junctional folds.
The depolarization is normall large enough to open a sufficient number of Na channels to exceed the threshold for an action potential.
What are the 4 types of Motor Unit Disorders?
- Motor Neuron Diseases (Cell Body)
- Peripheral Neuropathies (Axon and Myelin)
- Disorders of the Neuromuscular Junction
- Myopathies (Primary Mucle Diseases)
What is ALS?
Amyotrophic Lateral Sclerosis
Symptoms:
- Usually starts with painless weakness in a single arm or leg.
- Trouble in Executing fine movements of the hand.
- This focal weakness then spreads over 3 or 4 years to involve all four limbs, as well as the muscles of chewing, speaking, swallowing and breathing. Fatal.
**Cause: **
Most cases involve both the upper and lower motor neurons; however the cause of 90% of the cases is not known.
Treatment:
No effective treatment.
Hereditary? - About 10% of cases are inherited in a dominant manner.
What is CMT Type 1?
Charcot-Marie-Tooth Disease Type 1
Demylinating neuropathy results in smaller, waker muscles. Conduction is peripheral nerves is slow, with histological evidence of demylination followed by remylination.
Progressive - No remissions or exacerbations.
Transfer: Autosomal Dominant
Can affect all peripheral myelinated nerves.
What is CMT Type 2?
Charcot-Marie-Tooth Disease Type 2
Has normal nerve conduction velocity and is considered an axonal neuropath without demyelination. Involves axonal degeneration.
Transfer: Autosomal Dominant
Can affect all peripheral myelinated nerves.
What is Myasthenia Gravis?
Myasthenia means muscle weakness.
Neuromuscular Junction Disease - Best Studied
Symptoms:
* Weakness greatest at the end of the day.
* Myasthenic Fatigue; Musckles that may seem normal at first become waker with continued use.
* Fatigue is exacerbated by physical activity, stress, illness, and heat.
* Can lead to death due to paralysis of respiratory muscles.
Autoummune disorder: Attacks Nicotinic AChRs
What are possible treatments of Myasthenia Gravis?
- Enhancement of Cholinergic Transmission (AChE inhibitors)
- Thymectomy
- Immunosuppression
Explain the full mechanism of Myasthenia Gravis?
What are 3 important difference between the parasympathetic and sympathetic nervous sytem?
- Location of preganglionic neuron in CNS
- Location/organization of autonomic ganglia
- Neurotransmitter/Receptor system at the synapse
The ____ is the key brain site for central control of the ____ nervous system?
The hypothalamus is the key brain site for central control of the autonomic nervous system?
What region of the hypothalamus facilitates the major control pathways?
Dorsal Longitudinal Fasciculus
Where do sympathetic preganglionic neurons originate from?
The cell bodies are located between T1 and L3 in the lateral horn of the spinal cord.
Sympathetic Nerves usually travel along ____.
Sympathetic Nerves usually travel along spinal nerves.
Where do Parasympathetic preganglionic neurons originate from?
Originate from the brainstem and sacral spinal cord and synapse with postganglionic neurons in “terminal” ganglia that are located near target organs.
The preganglionic parasympathetic fibers originating in the brain distribute with ____.
The preganglionic parasympathetic fibers originating in the brain distribute with Cranial Nerves.
What four cranial nerves do parasympathetic fibers distribute with?
- Oculomotor Nerve (CN III)
- The Facial Nerve (CN II)
- The Glossopharyngeal Nerve (CN IX)
- The Vagus Nerve (CN X)
What are the 3 fates of a preganglionic sympathetic neuron?
What does the Pelvic Viscera consist of?
- Enteric Nervous System
- Renal System
- Bladder
- Organs in the Abdomen
Describe the different neurotransmitter released in the different pathways of the ANS.
What type of nicotinic acetyl choline receptors are on the post ganglionic neurons of the sympathetic and parasympathetic nervous systems?
The synapse between pre and post ganglionic neurons.
nAChR (a3B4)
Describe the various effects of the sympathetic and parasympathetic system on different organs.
What is the Adrenal Medulla-Pathway?
Cromaffin cells have nicotinic Ach receptors. They reside near blood vessels and release epinephrine into the bloodstream.
Epinephrine enhances the ability of the sympathetic division to broadcast its output throughout the body.
Can NE and E activate all andregenic receptors?
Yes, All 5
What is the fight or flight response?
One of the most dramatic sympathetic responses.
In response to fear, exercise, and other types of stress, the sympathetic divisino produces a massive and coordinated output to all end organs simultaneously, and parasympathetic output ceases.
Mass response is a primitive mechanisms for survival.
What are the physiological effects of the fight or flight response?
- Heart Rate Increases
- Dilation of blood vesels to heart and muscles (arms and legs)
- Liver produces glucose, energy for muscle contraction.
- Blood is diverted from gastrointestinal track to skeletal muscle.
What happens when the flight or fight response is triggered by minimal stress or spontaneously?
Causes a Panic Attack
Nerve Agent: Block of AChE
What meds can stop a panic attack?
- Clonazepam (Rivotril)
- Alprazolam (Xanax)
- Lorazepam (Ativan)
- All Benzodiazepines -> Enhance GABA-A mediate inhibition.
- Propanolol (B-Blocker) - Stop the Sympathetic Response
What are the multiple points of contact postganglionic neurons make with their target called?
Varicosities
Explain Neurotransmission at Sympathetic Varicosities.
Explain Neurotransmission at parasympathetic Varicosities.
What are the symptoms of Dysautonomia or Autonomic Neuropathy?
- Digestive symptoms: diarrhea, constipation, feeling less hungry or full too quickly, nausea, throwing up undigested food, trouble swallowing, heartburn.
- Heart and Blood Vessel Symptoms: Dizziness of fainting when you stand up, very fast heart rate, especially during excercise, high blood pressure.
- Urinary Symptoms: Trouble starting or lack of control, urinary tract infections.
- Body Temperature Symptoms: Night sweats, sweating too much or too little
- Sexual Symptoms: Impotence, low sex drive
- Lung Symptoms: Shortness of Breath
- Vision Symptoms: Trouble adjusting betwen bright and dark.
What other pathologies is Dysutonomia associated with?
- Diabetes
- Parkinsons Disease
What is Horner Syndrome?
The Combination of unilateral ptosis (drooping eyelid), miosis (small pupil), and anhidrosis (lack of sweating).
All these places have sympathetic innervation.
Cause: Results from the loss of the normal sympathetic innervation oe side of the face.
