Exam 1 Flashcards
What is the definition of a stroke?
Physiological condition which occurs when the blood supply to part of
the brain is interrupted leading to insufficient supply of oxygen and
nutrients to the area
How do strokes first present?
Alteration in consciousness ■ Headache ■ Aphasia ■ Facial weakness or asymmetry ■ Incoordination ■ Ataxia ■ Visual loss, vertigo, double vision, unilateral hearing loss, nausea, vomiting, photophobia, phonophobia
What does the FAST mean?
F- face dropping
A- arm weakness
S- speech difficulty
T- time to call 911
What are the different types of strokes?
Focal Ischemic
Global Ischemic
Hemorrhagic
What is a Focal Ischemic stroke?
Is the result from vessel occlusion which causes a focal defect
Ct scan shows Edema presents with reduced density
(darker region)
How is acetylcholine affected with AD?
Changes neurotransmission. ■Decreases in acetylcholine in AD patients – Choline acetyltransferase synthesis decreases – Loss of neurons in the basal nucleus of Meynert decreases projections – Common treatment in AD are acetyl cholinesterase inhibitors, drugs keep it around longer in neuron so that you end up with same amount, works early on
What is a Global Ischemic stroke?
It is the Global reduction in blood flow (for example through cardiac
insufficiency
What is a Hemorrhagic stroke?
It is the Rupture of a blood vessel
A CT scan shows Iron in blood absorbs Xrays- creates hyperdense
white region
Why is lack of blood flow so detrimental?
■ Brain consumes massive amount of energy to maintain ion gradients! – But only stores a 120 second ATP supply – And neurons have no glycogen storage – Evolutionary trade off: increased neuronal number but constant need for nutrient perfusion
What generates the most ATP?
Oxidative phosphorylation generates the most
ATP, requires both glucose and oxygen which is delivered through the circulatory system.
ATP usage is in neurons
What provides the brain with oxygen and glucose?
Cerebral vascular provides the brain with
glucose and oxygen
Diffusion requires vessel to be within 50um of
neurons - Lots of capillaries!!
What is the typical clotting cascade?
bleeding happens- clotting factors- Prothrombin- Thrombin- Fibrinogen (soluble)- Fibrin(insoluble)
What is the typical cascade of clot degradation?
- TPA (a clot buster and FDA approved treatment of stroke)
- Plasminogen- plasmin
3.Fibrin- degraded
clot breaks up
What are the two types of blood clots?
■ Intrinsic
– Triggered by internal damage to the blood vessel
■ Extrinsic
– Triggered by trauma
– Of interest for stroke because of atherosclerosis
What is Atherosclerosis?
Build up of fatty deposits in large
and medium-sized arteries leading
to the formation of plaques
■ Severe build-up blocks blood flow
What is the Pathogenesis of plaque formation?
■ Foam cells weaken the arterial wall
■ Smooth muscle cells invade the plaque and form a fibrous cap
■ If the cap ruptures, an embolus is released, travels through the blood stream
– If it gets stuck- ischemic stroke
What is the Ischemic Cascade?
Theres a flow disturbance Rapid: O2 depletion energy failure terminal depolarization ion homeostasis failure
Secondary:
excitotoxicity
SD-like depolarizations
disturbance of ion homeostasis
Delayed:
inflammation
apoptosis
The Ischemic Cascade leads to what?
O2 and glucose
depletion lead to energy failure
■ ATP cannot be synthesized in adequate amounts
Loss of resting
membrane potential
■ Na+/K+ stops functioning
– Resting membrane potential slowly lost
What is Terminal depolarization in the ischemic cascade?
■ Neurons hit depolarization threshold within minutes ■ Unregulated action potentials begin
What is the Calcium influx in the Ischemic Cascade?
■ Action potential initiates the opening of the voltage-gated Ca2+ channel at the axon terminal – Further depolarization of the neuron Look at slide
What causes Neuronal death?
Neuronal death in the core results primarily from edema and necrosis ■ As ions enter the cell, osmosis occurs leading to cell swelling (edema) ■ Cellular membranes are ruptured ■ Necrosis ensues
(Mitochondrial damage, cell membrane disruption, production of free radicals, cytoskeletal breakdown, and DNA fragmentation)
What causes Neuronal death?
Neuronal death in the core results primarily from edema and necrosis ■ As ions enter the cell, osmosis occurs leading to cell swelling (edema) ■ Cellular membranes are ruptured ■ Necrosis ensues
What is the Ischemic penumbra?
■ Ischemic penumbra- tissue surrounding the core that is perfused insufficiently by collateral vessels ■ Focus of intervention strategies – Can be saved if perfusion occurs within 6- 24 hours Excitotoxicity leads to cell death in the penumbra
What are treatments for strokes? (tPA)
■ Intravenous administration of tPA protein to
promote clot breakdown
■ Must be administered within the first 4.5
hours
What are treatments for strokes? (Mechanical thrombectomy)
■ Angioplasty
■ Physical removal of the clot
through endovascular surgery
with a stent
What is an experimental stroke treatment?
NMDA blocker
look at slide
What is action potential?
Electrical signals travel down the axon as
ion channels open and close
Every cell has a voltage (difference in electrical charge) across its plasma membrane called a membrane potential
■ The resting potential is the membrane potential of a neuron not sending signals
What is resting membrane potential?
Maintained predominantly by the potassium leak channel
– Aided by sodium leak channel and Na+/K+ pump
Gated ion channels are responsible for electrical signaling
What is hyperpolarization?
The inside of the cell more negative
– For example, K+ exiting the cell or Cl entering the cell
Graded hyperpolarizations produced
by two stimuli that increase
membrane permeability to K+.
What is depolarization?
The inside of the cell becomes more
positive
■ For example, Na+ channels open and
Na+ diffuses into the cell
Graded depolarizations produced
by two stimuli that increase
membrane permeability to Na+.
What is action potential concerning polarization?
An action potential is an extreme depolarization
of the neuron
(c) Action potential triggered by a
depolarization that reaches the
threshold.
What is the first step of an action potential?
Resting state: Voltage gated Na+ and K+ channels are closed; resting potential is maintained by ungated channels (not shown).
What is the second step of an action potential?
Depolarization: A stimulus (ligand) opens some Na+ channels; if threshold is reached, an action potential is triggered.
What is the third step of an action potential?
More Na+ channels (voltage gated) open, K+ channels remain closed; interior of cell becomes more positive. Membrane polarity becomes the reverse of resting state. 3
What is the fourth step of an action potential?
Repolarization: voltage-gated Na+ channels close and inactivate; voltage-gated K+ channels open, and K+ rushes out; interior of cell becomes more negative than outside.
What is the fifth and final step of an action potential before the resting state?
The voltage-gated K+ channels close relatively slowly, causing
a brief undershoot.
Why do action potentials only work in one direction?
-Inactivated Na+ channels behind the zone of depolarization prevent the action potential from traveling backwards -During the refractory period after an action potential, a second action potential cannot be initiated because of the temporary inactivation of the Na+ channels
Why do action potentials only work in one direction?
-Inactivated Na+ channels behind the zone of depolarization prevent the action potential from traveling backwards -During the refractory period after an action potential, a second action potential cannot be initiated because of the temporary inactivation of the Na+ channels
