Midterm 2 Flashcards
Cornea. Outermost layer. Transparent and Curved. Refraction and focusing power. Reversible damage is fairly rare but includes short term exposure to high sunlight.
Aqueous Humor. liquid located behind the cornea. source of nutrition for cornea and lens. Made in the ciliary body and trained in the Schlemm’s Canal and trabecular network. Important in glaucoma.
Pupil. The hole in the iris that permits light to enter the eye. It appears black when looking at the eye.
Lens or Crystalline Lens. composed of long, onion-layered prism cells with crysatllin proteins. Transparent and flexible. Connected to the ciliary body by zonular fibers that radiate outward and provide tension. Associated with cataracts.
Iris. Modified portion of the choroid layer. Color part of the eye. Forms the angle associated with glaucoma with the cornea. Two sets of smooth muscle. Set that radiates outward from pupil and are sympathetically innervated (norepinephrine) causing dilation of pupil. Second set circumvents the pupil and are parasympathetically innervated (acetylcholine) and cause constriction of pupil.
Zonular Fibers. Attach the lens to the ciliary body.
Vitreous Body. Usually clear gelatinous layer. Contain “floaters” which are impurities that usually float around. If they are located right above retina will cast a shadow and cause vision disturbances. Sudden changes in floater appearances may indicate a hemorrhage or retinal detachment.
Sclera. outermost layer of eye. modified anteriorly to form the cornea
Choroid. Between the sclera and retina. contains the blood vessels. Blackish-brown to prevent reflection.
Retina. nervous tissue containing rods and cones.
Optic Disk. location where the axons (all are afferent) of the retina converge and exit the eye. Is a blind spot.
Physiology of Glaucoma
Degeneration of afferent axons in the retina near the optic disk due to increased intraocular pressure caused by excessive accumulation of aqueous humor.
Begins with retinal ganglion cell degeneration followed by their cell bodies.
Glaucoma Diagnosis
- Tonometry: measuring tension in the eye. Press against the white of eye to check pressure or you have a machine that blows a puff of air to see the amount of indentation.
- Can look at blood vessels because of changing shape of optic disk
- Retina imaging
Open Angle Glaucoma
90% of glaucoma. Age is biggest risk factor. Slowly and painlessly progresses. Does not cause symptoms until permanent damage has occurred. Cause is improper drainage of aqueous humor.
Closed Angle Glaucoma
more common in younger people. Sudden, painful onset. Iris becomes pushed over against the cornea and the aqueous humor can’t get to the trabecular network. Usually caused with sympathetic innervation causing sudden dilation of pupil. Also have dilated blood vessels around the edge of the cornea. Treatment involves constricting pupil.
Alpha2 Adrenergic Receptors in Glaucoma Treatment
decrease aqueous humor formation at the ciliary body and increase outflow.
Beta Adrenergic Antagonists in Glaucoma Treatment
decrease aqueous humor formation at the ciliary body (in a different mechanism than Alpha2 adrenergic agonists) Example is timolol.
Prostaglandin Analogs in Glaucoma Treatment
Increase the drainage of aqueous humor. Example is latanoprost.
Cholinergic (muscarinic) Agonists in Glaucoma Treatment
decrease aqueous humor formation and constrict the pupil which is used in closed angle glaucoma. Pilocarpine is example.
Carbonic Anhydrase Inhibitors in Glaucoma Treatment
reduces the formation of HCO3 - which in turn reduces solute and thus fluid secretion at the ciliary body.
Laser Trabeculoplasty in Glaucoma Treatment
treatment option where laser is aimed at the trabecular network to increase the flow through the network. Effect is not permanent.
Conventional surgery in Glaucoma Treatment
can be used to create an opening with which the aqueous humor can drain from the eye.
Cataracts Symptoms, Causes and Treatment
Region of the lens becomes cloudy.
- Causes: Biggest cause is age and genetics. Can be promoted by diabetes, UV light exposure, trauma and heavy glucocorticoid use.
- Symptoms include cloudy vision with an increase in glare which produces a halo like affect.
- Completely resolved by surgery: emulsify lens and suck it out then replace with a new custom fitted lens that will also repair any other prior vision problems. New lens cannot accommodate for close-up vision though.
Measuring Focusing Power
diopters are used to measure the focusing power of the lens. 1 diopter has the focusing power of 1 meter. 2 diopters is 1/2 meters etc. The eye is about 1/60th
Focusing on objects close and far away
As an object moves closer to the eye the focal point is moved back away from the front of the eye.
As an object moves further from the eye the focal point is shifted toward the front of the eye.
Lens in Focusing Power of Eye
Lens has about 20 diopters but has the capacity to increase the number of diopters by contracting ciliary muscle to make the lens more convex.
A more convex lens causes the focal point to move forward toward the front of the eye. This is used in close-up vision. Parasympathetic control over ciliary muscle to contract causing more floppy lens that can bulge.
Myopia
eyeball is too long. most common.
An image at infinity doesn’t focus on retina but instead in front of retina. Therefore if the ciliary muscle contracts it makes vision worse.
Need fewer diopters to move image back from front of eye. Result is a concave lens and negative diopters. Can see close-up images much better though (built in magnifying glass).
hyperopia
Eyeball is too short.
Image at infinity focuses behind retina. If ciliary muscle is contracted it helps but causes eye strain and it is hard to focus on things closer up.
Need positive diopters to move the image closer to the front of the eyeball, need a convex lens.
Astigmatism
The cornea has different curvatures on different axes. not symmetrical. Solution is to have different curvatures in lens of glasses.
Presbyopia
The lens gets stiff from age so there is little accommodation for close-up vision. Occurs to everyone in late 40’s - early 50’s. Is the loss of the ability of the lens to bulge when the ciliary muscle contracts.
Fovea
direct center of the retina about 1 mm in diameter that has a very high density of cones. Responsible for detailed fine vision and color vision.
Rods
located in peripheral of retina and are incredibly sensitive. black and white but have extra sensitivity to light. Responsible for night vision.
Neuronal Process of Light
Light has to pass through the ganglion cells to the bipolar cells to the rods and cons where it is absorbed by rhodopsin. This causes retinal protein to detach and activate a G protein activating a phosphodiesterase. This phosphodiesterase destroys cGMP and closes a Na+ ion channel. Repolarization causes release increased release of the neurotransmitter glutamate which causes an action potential.
Location of Action in Diabetic Retinopathy
Retinal pigment epithelium supports the rods and cons. Under that is the choroid layer which is painted black and contains the blood vessels. In diabetic retinopathy damage is done to the choroid layer.
Non-Proliferative Stage in Diabetic Neuropathy
leaky blood vessels in the choroid layer leads to macular edema and lipid accumulation.
Proliferative Stage in Diabetic Neuropathy
angiogenesis (abnormal growth of blood vessels) which usually begins at the optic disk. Response to abnormal growth factor VEGF. Get bleeding (hemorrhage) into the vitreous body and it can lead to retinal detachment.
Treatment for Diabetic Retinopathy
control hyperglycemia,
anti-VEGF injection,
glucocorticoid injection,
laser photocoagulation,
vitrectomy.
Retinal Detachment Symptoms and Treatment
Symptoms: all of a sudden get increased amounts of floaters, little flashes of light, curtain starts falling (black edge that is moving over field of vision).
Treatments:
photocoagulation to put retina back in place
vitrectomy and fill with bubble of inert gas to push retina back in place.
Two Types of Macular Degeneration
- “Dry” accounts for about 90% and is the gradual thinning and loss of rods and cons. Vision starts to become blurred. Drusen deposits of proteins and lipids appear in the retinal pigment epithelium.
- “Wet” accounts for about 10% and involves angiogenesis in choroid layer. Distortion of the retina leads to weird vision with grid (straight lines look curved).
Treatment of Macular Degeneration
- wet and dry option is AREDS 2 formulation which is a vitamin/supplement
- wet only options: Anti-VEGF, laser photocoagulation, photodynamic therapy (injected into systemic circulation and adheres to broken blood vessels and is only activated by light).
Diagnostic Tools for Macular Degeneration
- Optical Coherence Tomography: Gives you an image of the thickness of the retina.
- Angiograms: image of retinal blood vessels.
Visual Information to the CNS
- nasal retina (closest to the nose) of one eye will cross to the opposite side of the brain at the optic chiasma.
- Temporal retina (closest to ear) of one eye will not cross to the opposite side of the brain at the optic chiasma.
Structure of Ear
Outer ear: tympanic membrane, external auditory canal
Middle ear: air filled, ossicles (malleus, incus, stapes) and the oval window (membrane that divides middle ear from inner ear)
Inner ear: cochlea is fluid filled, basilar membrane with hair cells (narrower and stiffer and thus responds to higher frequencies at the oval window end).
Flow of Sound
Sound strikes tympanic membrane which then moves, moving the lever like system of the ossicles. The ossicles act like a piston to apply pressure to the oval window, which vibrates the basilar membrane.
Sensory Transduction
sound energy to action potential. responsibility of basilar membrane.
- Hair cells (neurons, nt is glutamate) are stuck to the basilar membrane.
- Projections at the top of hair cells called stereocilia have mechanically gated ion channels that release glutamate when the stereocilia bumps into the tectorial membrane sitting stationary above the basilar.
- Glutamate release results in stimulation of second neurons which go to the vestibulo-cochlear nerve.
Conduction Deafness
inner ear doesn’t work. alternate pathway to cochlea is bone conduction. Use a hearing aid right behind the ear so sound conducts into bone then to cochlea.
Otosclerosis
common cause of deafness. Excess bone growth that freezes stapes in place. Caused by a dominant gene but see different levels of intensity.
Sensorineural Deafness
also called sensory deafness. degeneration of hair cells usually caused by prolonged exposure to noise. Degeneration is not uniform so hearing loss is dependent on pitch.
causes: presybcusis (atrophy due to age), drugs (amino-glycosides, diarrhetic, antimalarial), viruses.
Vestibular System
senses rotational and linear acceleration
causes motion sickness and controls eyes.
Nystagmus
eye reflex that allows your eyes to compensate for movements of the body. When rotating, eyes track back slowly then jump ahead.
Meniere’s Disease
also called endolymphatic hydrops.
three symptoms - vertigo, sensorineural deafness, tinnitus.
usually due to too much fluid in vestibular system and tends to go away without any permanent hearing loss.
Utricle and Saccule
sense linear acceleration.
otoconia: stones that when moved by inertia cause hair cells to move.
benign paroxysmal position vertigo: where otoconia break off and get into a canal which causes fluid loading. When you lie down you get really dizzy. Easy to cure, just have to move otoconia through canal and back into utricle.
Taste and Olfactory Receptors
Neuron Receptors for bitter and sweet taste as well as the olfactory neurons are 7 transmembrane domains. The taste neurons activate trimeric G proteins.
Anatomical Methods of Studying the Brain
grey matter: contains neural cell bodies. nucleus is a collection of cell bodies that are anatomically defined
white matter: contains the axons of neurons. A tract is a bundle of axons in the CNS.
Brodmann’s areas: regions of the brain defined by cellular architecture.
Broca’s Aphasia
expressive aphasia: speech is described as being telegraphic only using single words with no fluency. Understand language when listening but have difficulty expressing language.
Wernicke’s Aphasia
receptive aphasia: affects comprehension but not production of language. No trouble producing word but will have a string of speech that has no meaning. And no ability to understand what is being said to them.
Global Aphasia
broader lesion in left hemisphere causing both Broca’s and Wernicke’s aphasia. Along with a speech deficit also see right side paralysis because the motor cortex runs between the two regions. And remember the lesion is on the left side of the brain so the paralysis is on the right side of the body.
Electroencephalography
EEG. record little changes in electrical potential differences on points on scalp (non-invasive).
alpha rhythms: relaxed (awake) with eyes closed. high amplitude waves with characteristic low frequency of 10 hertz. synchronous activity.
beta rhythms: alert, eyes open. high frequency, low amplitude. desynchronized activity.
Functional Imaging
radioactive tracers to track activity of regions of the brain. more active parts of the brain will have higher blood flow.
fMRI measures brain activity indirectly by measuring changes in blood flow between different regions. measure levels of deoxyhemoglobin.
Amnesia Patient HM
subject is HM. seizure activity as child. removed bilateraly the medial temporal lobe to eliminate seizure activity. Thus removing the hippocampus (and also the amygdala).
result was severe anterograde amnesia (anterograde means going forward).
Working memory and long-term memories not affected. Consolidation of information into long-term memories missing and had no declarative (explicit) memory.
Morris Water Maze
experiment in rats developed to test spacial memory. Rats swam in opaque water with a hidden platform. Normal rates after several trials were able to find the platform almost immediately. Rats with their hippocampus removed did not have the capacity to find the hidden platform.
long-term potentiation
found in electrophysiological studies shows that most common form of synaptic plasticity is long-term potential (LTP). Cell A connects to Cell B via an excitatory synapse. stimulate cell A and record EPSP in Cell B. to induce LTP stimulate cell A with high frequency. When recorded you still get a higher EPSP. Activity of synapse must be paired with a strong depolarization at Cell B. NMDA channels with glutamate are responsible.
Procedural Memories
unconscious, skills, habits. HM did not have affected procedural memory. Mirror drawing task as diagnostic. Use mirror to trace a star, expect improvement after multiple attempts.
Alzheimer’s Disease Diagnosis
postmortem is only definitive diagnosis.
amyloid plaques: extracellular accumulations of A-beta proteins.
neurofibrillary tangles: intracellular accumulations of hyperphosphorylated tau.
Amyloid Hypothesis in Alzheimer’s
describes the cause of neurodegeneration
accumulation of A-beta in an aberrant way over time causes neurodegeneration.
Amyloid precursor protein is normally found in synapses and A-beta is generated with APP is cleaved.
Thought that the most toxic of the cleaved products are soluble oligomers of A-beta, not the plaques that are physically seen.
Genetic Link in Alzheimer’s
Best known genetic risk factor for Alzheimer’s is a variant of the gene coding for apolipoprotien E.
Down Syndrome and Alzheimer’s
Gene for APP located on Chromosome 21. Therefore, in people with Down Syndrome (1 extra Chromosome 21) normally see early onset of Alzheimer’s
Treatment for Alzheimer’s
no disease modifying drugs. Only have drugs that can help with symptoms
cholinesterase inhibitors: increase Ach at synapses. Regions of the brain affected in Alzheimer’s usually use ACh as neurotransmitter.
memantine: NMDA receptor antagonist which reduces excitotoxicity (higher than normal levels of glutamate released activating NMDA channels in neighboring cells)
The Two Stages of Sleep
NREM: non-REM sleep. high amplitude and low frequency delta rhythm waves. Referred to as slow-wave sleep.
REM: also referred to as paradoxical sleep. rapid eye movement. desynchronized EEG. Atonia (complete lack of skeletal muscle tone), associated with vivid dreaming.
Arousal Promoting Nuclei
TMN (histamine), RAPHE (serotonin) and LC (norepinephrine).
diffuse excitatory projections. Act on GPCR (slow synaptic transmission). Make direct inhibitory connection to the VLPO (sleep-promoting) nuclei.
Sleep-Promoting Nucleus
VLPO (GABA). inhibitory neurotransmitter with direct and fast synaptic transmission to arousal promoting nuclei.
Orexin Releasing Nucleus
LHA nuclei. helps maintain activity during arousal by exciting the arousal-promoting nuclei. direct excitatory connections. maintains wakefulness.
Circadian Rhythm and the suprachiasmatic nucleus
suprachiasmatic nucleus is the intrinsic pacemaker.
input from the retina to the suprachiasmatic nucleus entrains pacemaker to daily light/dark cycle.
suprachiasmatic nucleus regulates release of melatonin from pineal body which promotes the sleep-wake cycle.
Stimulants
promote wakefulness.
amphetamines: increase NE, DA, serotonin
modafinil (Provigil) and armodafinil (Nuvigil) increase NE, DA and maybe also histamine and serotonin. less likely to be addictive, and less side effects than amphetamines.
caffeine: adenosine antagonist. adenosine inhibits neural activity.
Hypnotics
promote sleepiness and work on GABA.
- benzodiazepines and Z-drugs (Zolpidem): GABA potentiators, work on separate site as GABA. Z-drugs have shorter half-life so may eliminate potential for addiction and abuse and reduce severe next-day drowsiness.
- GHB (Xyrem) works via GABA. specifically used in treatment of narcolepsy.
- suvorexant (Belsomra) orexin antagonist and only recently approved. may be much more specific for brain only.
- antihistamines
- ramelteon (Rozerem) melatonin agonist.
Insomnia
symptoms: increased sleep latency (trouble falling asleep), decreased sleep efficiency (trouble staying asleep), poor sleep quality
Causes: hyperarousal (increased activation of arousal promoting nuclei).
Treatment: behavioral therapy. hypnotic drugs including Z-drugs, orexin antagonist (suvorexant) or melatonin agonist (ramelteon)
Symptoms of narcolepsy
excessive daytime sleepiness, disturbed nighttime sleep, sleep paralysis (wake up in morning and still experiencing atonia), dream-like hallucinations while awake (hypnagogic hallucinations), rapid transition into REM sleep, cataplexy (loss of skeletal muscle tone while awake).
Cataplexy cause
caused by inappropriate expression of REM atonia controller which excites an inhibitory interneuron which turns off somatic efferent neurons.
Cause of narcolepsy
deficiency in orexin signaling.
Treatment of Narcolepsy
excessive daytime sleepiness treated with stimulants
cataplexy treated with antidepressants which increase NE and serotonin which prevent the inappropriate REM atonia controller activation.
disturbed sleep treated with Xyrem (GHB) which consolidates sleep.
REM sleep behavior disorder
vigorous movement (dream reenactment) during REM sleep.
parasomnia - abnormal behavior during sleep
diagnosis: polysonography. includes EEG and EMG.
most people with REM sleep behavior disorder go on to develop diseases with abnormal alpha-synuclein accumulations, like Parkinson’s.
Chronic Traumatic Encephalopathy
(CTE)
long-term consequence of repeated concussions.
concussion = alteration in neurological function following head injury. symptoms include dizziness, headache, confusion, temporary amnesia, disorientation.
deposits of tau (protein found in neurofibrillary tangles)
