Midterm 2: Buzzword Bingo Flashcards
Aphasia with decreased fluency, normal comprehension, decreased naming, decreased repetition
Broca’s aphasia
Clinical condition indicated by Brudzinski sign
Meningitis
Brudzinski sign is a test of nuchal rigidity. On passive flexion of neck, the patient will spontaneously and unconsciously flex legs and thighs.
Kernig sign
Flex patient’s hip to 90 degrees. In a positive Kernig sign, you won’t be able to extend that leg without the other leg flexing. This is also highly specific for meningitis (but not sensitive).
CNS inflammatory condition with abnormal brain function
Encephalitis - inflammation of the brain parenchyma.
Poorly demarcated focal infection of the brain
Cerebritis
Well-demarcated focal infection of the brain
Abscess
CNS inflammatory syndrome presenting with motor, sensory, autonomic dysfunction below the level of the lesion
Myelitis
Type of CNS inflammation indicated by a ring-enhancing lesion on head CT (referring to the clinical syndrome, not the specific pathology)
Abscess or cerebritis
Most common causes of bacterial meningitis in neonates
Gram negative rods, Group B strep
Most common causes of bacterial meningitis in kids
1) N meningitidis, 2) S pneumo
Most common causes of bacterial meningitis in adults
1) S. Pneumo, 2) N. Meningitidis
Most common causes of bacterial meningitis in older adults
N. Meningitidis, S. Pneumo, listeria
Appropriate empiric ABX for a neonate with suspected bacterial meningitis
Ampicillin + cefoxitime or aminoglycoside
Appropriate empiric ABX for a child or adult with suspected bacterial meningitis
Vancomycin + a third-generation cephalosporin
Appropriate empiric ABX for an older adult with suspected bacterial meningitis
Vancomycin + third-gen cephalosporin + ampicillin
What is the prognosis of a brain abscess?
10% mortality, 30% lasting deficits
Most common cause of fatal viral encephalitis
HSV viral encephalitis, involving temporal lobe. Presents like bacterial meningitis, but with seizures. Tx with IV acyclovir
Name the most likely etiology: Lumbar puncture shows very high PMNs, low glucose, high protein
Bacterial etiology
Name the most likely etiology for CNS infection based on lumbar puncture: high lymphocytes, normal glucose, high protein
Viral etiology
Name the most likely etiology for CNS infection based on lumbar puncture: normal to high mixed WBCs, normal glucose, high protein
Abscess
Red flags indicating a thunderclap headache
Sudden onset, very severe, hits its maximum intensity immediately
Presentation of a headache that doesn’t require imaging
Episodic with headache-free days, fulfills migraine criteria, onset <50 years
Serious causes of headache that can still have normal imaging
Temporal arteritis, pseudotumor, glaucoma, subarachnoid hemorrhage (if you delay the CT)
Motor unit
1 motor neuron and all the muscle fibers that it innervates
Neurotransmitter at the NMJ
Acetylcholine
Enzyme important for ACh synthesis
ChAT
This phenomenon is produced by the spontaneous release, without stimulation, of a single synaptic vesicle at the NMJ.
Miniature endplate potential (mEPP)
About how many quanta of ACh are released by an action potential?
200-300
Membrane potential of muscle
Around -85 mV
What is an EPP?
The sum of many mEPPs, formed when an action potential releases a large number of synaptic vesicles into the NMJ. It depolarizes the motor endplate by 30-50 mV.
Nicotinic ACh receptor channels are permeable to which ions?
Sodium and potassium, although the concentration gradient is such that the depolarization due to the EPP is driven by sodium.
What contributes to the high safety factor in motor units, and what does that mean?
A high safety factor means that every AP in the motor neuron will produce an AP in the associated muscle fibers. This is due to the high number of vesicles released, high density of nAChR at the synapse, and lack of inhibitory motor neurons.
How does ACh cause the EPP?
2 molecules of ACh bind to the nAChR, leading to a conformational change and opening of the channel pore to Na+ and K+ (although Na+ has a greater driving force, leading to a net excitatory event).
How is the signal at the NMJ terminated?
ACh is broken down by acetylcholinesterase, which hydrolyzes it once it dissociates from the receptors. It can also diffuse out of the NMJ.
Can the motor endplate generate an AP?
No - it has no voltage-gated sodium channels
How is an AP generated in muscle?
Depolarization from the EPP spreads as a local current to adjacent muscle membrane, which can evoke an EP
MOA of gallamine
Gallamine is a competitive ACh inhibitor. It competitively binds to the nAChR binding site for ACh, with higher affinity, blocking the development of EPPs. This causes paralysis.
How is gallamine used clinically?
Paralytic drug for use in surgery
MOA of succinylcholine
Depolarizing blocking agent: occupies nAChR for longer than ACh, causing an initial EPP/AP, but then doesn’t dissociate, leading to Na+ channel inactivation and desensitization of the nAChR
How can you reverse the effects of succinylcholine?
Acetylcholinesterase
How do anticholinesterases cause problems?
Anticholinesterases (sarin or nerve gas) block acetylcholinesterase, leading to long-term desensitization and Na+ channel inactivation
How are anticholinesterases used medically?
To terminate action of competitive inhibitors like gallamine
MOA of the AED vigabatrin
Irreversibly inhibits GABA transaminase
MOA of tiagabine
Blocks GABA transport out of the synaptic cleft by inhibiting GAT-1
MOA of valproate
Increases GABA concentration and decreases Na+ channels
MOA of topiramate
blocks Na+ channels, increases GABA action, and inhibits kainate receptors
MOA of gabapentin
Blocks high-voltage-activated calcium channels in pre synaptic terminal
MOA of perampanel
Non-competitive AMPA receptor antagonist that decreases fast excitatory transmission
MOA of phenobarbital
blocks AMPA receptors at the upper end of its therapeutic dose
MOA of felbamate
Blocks NMDA receptors
MOA of benzodiazepines
Make it easier for GABA-A chloride channels to open
Guiding principles for choosing a second AED after the first one fails to control epilepsy
Pick one with a different MOA from the first drug
MOA of carbamazepine, oxcarbazepine, phenytoin, lamotrigine
Prolong inactive state of sodium channels
MOA of lacosamide
Changes the conformation of sodium channels to speed up inactivation
Why choose oxcarbazepine over carbamazepine in terms of side effects?
Carbamazepine is metabolized to a stable epoxide by cytochrome p450, and that epoxide is responsible for most of the toxicity (plus tons of drug interactions). Oxcarbazepine doesn’t form an epoxide, and is more soluble.
The older benzodiazepine clobazam can’t be paired with cannabidiol - why?
Increases a toxic metabolite
Which glutamate receptor is implicated in seizure-like discharges?
AMPA receptors
MOA of levatiracetam
Binds to a membrane glycoprotein in synaptic vesicles containing glutamate and prevents/slows release of glutamate
What makes a good rational polypharmacy combination with lacosamide?
Traditional sodium blockers - the traditional ones prolong the inactive state, and lacosamide changes the speed of inactivation to make it occur sooner.
Large muscle fatigue caused by antibodies against Ca++ channels at presynaptic terminals
Lambert-Eaton syndrome
Fibrous tissue surrounding an entire muscle
Epimysium
Fibrous tissue surrounding muscle fascicles
Perimysium
Tissue surrounding individual muscle fibers
Endomysium
Order the calcium concentrations of the following compartments: extracellular fluid, sarcoplasmic reticulum, myoplasm
Sarcoplasmic reticulum > extracellular fluid > myoplasm
How many T-tubules are associated with each sarcomere (between its z lines)?
2
Why can’t a single muscle twitch have maximal force?
Calcium removal is always more rapid than the process of troponin saturation, so twitch force is always partial because troponin never becomes fully saturated.
Describe the layout of voltage-sensing molecules on the T tubule
Dihydropyridine receptors (L-type calcium channels, but function as voltage sensors) are clustered in tetras.
Describe the receptors on the SR that allow for calcium release from the SR
Ryanodine receptors - calcium release channels. These are positioned pretty much right below dihydropyridine receptors, and then there’s an unpaired one next to it.
Describe the mechanical hypothesis of EC coupling
Depolarization leads to a conformational change of the dihydropyridine receptor, which pulls open the ryanodine receptors, leading to calcium release
Most common genetic myopathy characterized by a dystrophin mutation
Duchenne Muscular Dystrophy, more severe than the related form of Becker MD
Patient can’t stand up from the ground without using hands - what is this called and what does it signify?
Gower’s maneuver - signifies hip girdle weakness
Muscle biopsy showing fibers replaced by fatty tissue, with rounded fibers, excess connective tissue, internalized nuclei
Duchenne muscular dystrophy
Histological features of congenital myopathies
Rods, cores, or central nuclei
Muscle biopsy showing mononuclear inflammatory cells in a perivascular/perifascicular distribution with perifascicular atrophy
Dermatomyositis
Muscle biopsy showing T cells invading non-necrotic muscle fibers and inflammatory response around individual muscle fibers
Polymyositis
Muscle biopsy showing various sizes of muscle fibers, muscle fiber necrosis, not a ton of inflammatory cells
Immune-mediated necrotizing myopathy
Muscle biopsy showing degeneration of fibers with vacuoles/inclusion bodies
Inclusion body myositis
