Documente Academic
Documente Profesional
Documente Cultură
Some MS2
Introduction/Learning Objectives
-Welcome to GSM; this is where youll begin to build the foundation necessary for tackling a myriad of
neuroscience problems as you go on with the block.
-Theres lots of material in this block, but it is very interesting material (in addition to being really HY), so learn
it the best you can.
-The material in Neuro is tested very heavily on the boards so dont blow this off. The Neuro chapter in FA has
almost as many pages as the Micro chapter, and youre well aware of how HY Micro is.
-Work on understanding the different tracts/pathways to see how everything fits together. Details matter, so
learn them.
-Your goal by the end of the block should be to be able to localize lesions and integrate the concepts with
complicated problems.
-Pay good attention to the pictures in this document.
-Therell be practice Qs to work through as you go through this document to reinforce key concepts.
Introduction/Learning Objectives
-Therell be slides with repeated information. Neuro does contain lots of information so this repetition is
mostly for the process of reinforcement. In addition, I use the repetition to keep peeling layers off different
concepts as I go from a more general overview to a more detailed discussion.
-The cerebellum is a fairly involved, but also somewhat HY subject so Ill talk about its inner workings many
times in different ways.
-A helpful study approach in Neuro is seeing how things fit together into one nice story, during the course of
our meeting (and with the slides), the goal would be to try to integrate as much as possible.
-I do understand the frustration that could arise with all the information being thrown at you (sorry..). All I can
suggest is to do the best you can and learn the slides in bits and pieces (i.e. learn 20 slides well, go do other stuff
for a while and then keep going).
-Youve come a long way in med school and you have the power to tackle and overcome whatever
lies ahead. Keep your chin up, work hard, enjoy the process, and youll reach your destination.
Q1
A 55 yo male presents to the Med19 Neuro ICU with complaints of progressive
weakness in his left lower and upper extremities. Which of the following is more
consistent with a lesion of Betz cells found in the primary motor cortex?
a.
b.
c.
d.
e.
Q1 Key
A 55 yo male presents to the Med19 Neuro ICU with complaints of progressive
weakness in his left lower and upper extremities. Which of the following is more
consistent with a lesion of Betz cells found in the primary motor cortex?
a.
b.
c.
d.
e.
Remember that Betz cells are Upper Motor Neurons that kickstart the Corticospinal
Tract that descends through the Centrum Semiovale-Corona Radiata-Cerebral
Peduncles-Decussation at the Pyramids-Lower Motor Neurons. Make sure you can
distinguish b/w UMN and LMN signs.
Q2
A 45 yo. Male presents to the ED with acute onset shortness of breath that began 3
days ago as bilateral muscle weakness in his lower extremities. He is rapidly intubated
when EMG studies reveal a decreased amplitude upon stimulation of his respiratory
muscles. Further history obtained from the patient would most likely reveal?
a.
b.
c.
d.
e.
Q2 Key
A 45 yo. Male presents to the ED with acute onset shortness of breath that began 3
days ago as bilateral muscle weakness in his lower extremities. He is rapidly intubated
when EMG studies reveal a decreased amplitude upon stimulation of his respiratory
muscles. Further history obtained from the patient would most likely reveal?
a.
b.
c.
d.
e.
Remember, acute onset paralysis should rule out anything with a chronic character.
This patient has Guillain Barre Syndrome secondary to C. Jejuni infection. A HY
buzzword to be aware of here is the CSF finding of Albuminocytologic Dissociation.
Q3
A 16 yo female is brought to the ED with severe swelling secondary to impaction of a 500 Lb
weight on her left wrist. PE reveals massive erythema but palpation reveals no pain in the affected
area. Muscle strength is 5/5 in all extremities but the patient (with her eyes closed) fails to
respond to an assessment of sharp sense on her shoulders and both upper extremities bilaterally.
Which of the following best represents the location of the lesion responsible for this patients
symptoms?
Q3 Key
The best answer is A.
This patient most likely has syringomyelia. Even if you dont know the actual disease,
the findings of intact muscle strength should help you rule out issues with the
Corticospinal Tract (option C) and the ventral horn (option B).
The mention of no response to assessment of sharp sense + the PE finding of no pain
upon palpation of the affected area (that a 500 Lb object landed on!) should raise giant
alarm bells in your mind relating to the loss of pain and temperature sensation. This is
controlled by the spinothalamic tract which crosses in the Anterior White Commissure
on its way to the cerebral cortex.
If you see the words, Cape like distribution on your exam, stop reading the question
and immediately pick the answer that corresponds to the spinothalamic tract.
Q4
A 42 yo male is brought to the ED by his family for new onset episodes of violence and
inappropriate speech. His wife also complains that over the last few months, he has
had weird dance-like movements in both lower and upper extremities. His father
died of an unknown neurologic illness at the age of 48. The underlying
pathophysiology behind this disorder is linked to?
a.
b.
c.
d.
Q4 Key
A 42 yo male is brought to the ED by his family for new onset episodes of violence and
inappropriate speech. His wife also complains that over the last few months, he has
had weird dance-like movements in both lower and upper extremities. His father
died of an unknown neurologic illness at the age of 48. The underlying
pathophysiology behind this disorder is linked to?
a.
b.
c.
d.
This man has Huntington's disease. The only real clues needed in this question are
the fact that his father died at 48 and then he (the son) started developing symptoms
at 42 (genetic principle-anticipation). Theres others but you really dont need them.
Brain Slice 8-Caudal Medulla with Associated Pathways (Level of the Olives)
Brain Slice 9-Caudal Medulla with Associated Pathways (Level of the Olives)
Brain Slice 10-Caudal Medulla with Associated Pathways (Level of the Olives)
Q5
The most likely location of the lesion in a patient that has lost all sensation completely
on one side of the body but still retains complete muscle strength is?
a.
b.
c.
d.
Thalamus
Posterior Limb of the Internal Capsule.
Medial Pons.
Precentral Gyrus of the cerebral cortex.
Q5 Key
The most likely location of the lesion in a patient that has lost all sensation completely
on one side of the body but still retains complete muscle strength is?
a.
b.
c.
d.
Thalamus
Posterior Limb of the Internal Capsule.
Medial Pons.
Precentral Gyrus of the cerebral cortex.
The best answer is the thalamus (remember that VPL resides here). A lesion of the
entire posterior limb of the internal capsule will result in motor deficits (not sensory
deficits). A medial pontine lesion would result mostly in cranial nerve dysfunction and
some motor symptoms from corticospinal tract damage. The precentral gyrus has the
primary motor cortex and nothing to do with sensation.
Q6
The complete loss of all sensation and cranial nerve function with the sparing of
extraocular muscle movement is associated with an aneurysm of which of the
following arteries?
Q6 Key
-The best answer is A (the basilar artery). Remember that the basilar artery supplies
the pons. Most people that have a stroke in this artery typically go into respiratory
failure and coma.
-Artery E represents Paramedian Pontine Arteries (dont worry about it).
-Artery F represents the AICA (lesion presents with problems in lateral pontine
structures like the facial nerve and the trigeminal nerve).
-Arteries D and C are the Superior Cerebellar and the Posterior Cerebral Arteries. It
may not hurt to remember the anatomical relationship b/w these arteries and the
Oculomotor Nerve (runs b/w both). Aneurysms in these arteries cause CN 3 palsies.
Also remember that a high intracranial pressure also leads to a CN 3 palsy secondary
to uncal (medial portion of the temporal lobe) herniation.
Q7
Facial droop of the lower face on the right, loss of sensation in the right upper
extremity, and an inability to understand the spoken word is most likely due to a lesion
of the?
a.
b.
c.
d.
e.
Q7 Key
Facial droop of the lower face on the right, loss of sensation in the right upper
extremity, and an inability to understand the spoken word is most likely due to a lesion
of the?
a.
b.
c.
d.
e.
The best answer is D. A lesion affecting all these structures could be a brainstem
lesion, but remember that understanding speech is a derivative of Wernickes area
which is in the temporal lobe. This localizes the lesion to the middle cerebral artery
which supplies this area.
Q8
An individual that has lost all motor activity in his left upper and lower extremities has
most likely lesioned which of the following vessels?
a.
b.
c.
d.
e.
Q8 Key
An individual that has lost all motor activity in his left upper and lower extremities has
most likely lesioned which of the following vessels?
a.
b.
c.
d.
e.
The best answer is C. This is a very HY point to be aware of. The Lenticulostriate
Arteries supply the posterior limb of the internal capsule which carries all the
information of the corticospinal tract from the cerebral cortex to the contralateral side
of the body.
Anesthesia Pharmacology
-In general, there are 3 main classes of anesthetics. The first class are the inhaled/IV anesthetics which are used
for general sedation, the second class includes the local anesthetics which are used for sensation control in
localized regions of the body, and the 3rd class includes the Neuromuscular blocking agents (NMBD) which are
for muscle paralysis.
-The NMBDs are used in situations where muscle paralysis is necessary (for example, in the setting of
intubation).
-There are 2 main classes of NMBDs with the first class being the Depolarizing NMBDs (succinylcholine), and
the Non-Depolarizing NMBDs (Tubocurarine and anything ending in Curium or Curonium). These drugs all
work at the level of the nicotinic Ach receptor.
-Succinylcholine is a Depolarizing NMBD that works as an agonist at Nicotinic Ach receptors. You may
wonder, if something is depolarizing muscle, how can it be a paralytic? Succinylcholine works by stimulating
the muscle repeatedly to the point where the muscle exhausts and is unresponsive to Ach. The initial
depolarization explains the fasciculations associated with the initial administration of the drug.
Anesthesia Pharmacology-contd.
-Under normal circumstances, depolarization of the the muscle makes the muscle fire with eventual resetting of
the muscle so it can fire again. Unfortunately, Succinylcholine is not degraded by Acetylcholinesterase, and
hence it stimulates the muscle for long periods of time, effectively preventing any form of muscle reset.
Succinylcholine is degraded by Pseudocholinesterase which exists in the serum (not at the synapse).
-Succinylcholine has a quick onset of action in addition to rapid clearance so its effects wear off quickly.
However, there is no reversal agent (unlike the ND NMBD that could be reversed with acetylcholinesterase
inhibitors that can lead to Ach crowding out the bound paralytic).
-Since Succinylcholine agonizes nicotinic Ach receptors (which are ion channels), it increases the extracellular
efflux of K+ (as any normal ion channel should operate), which can give rise to hyperkalemia. Succinylcholine
is contraindicated in conditions that already predispose a patient to hyperkalemia (burns for example) as too
much K+ can stop the heart. Another HY SE of Succinylcholine is malignant hyperthermia (a hypermetabolic
state-picture a person that ingests too much thyroid hormone).
-A few patients have an atypical pseudocholinesterase that has a reduced ability to break down succinylcholine.
This occasionally puts patients into severe paralysis for many hours.
Anesthesia Pharmacology-contd.
-The Nondepolarizing NMBD are essentially competitive antagonists of the Nicotinic Ach receptor. These
agents can be reversed with the administration of an AchE inhibitor (basically anything ending in stigmine on
your test).
-Since acetylcholine is also a muscarinic agonist, administration of AchE inhibitors drops the HR. This can be
counteracted by giving a muscarinic antagonist like Atropine.
-This is very LY for your test (but who knows!), but Vecuronium and Rocuronium are eliminated by the liver,
Pancuronium is cleared by kidneys, and Atracurium/Cis-Atracurium is cleared in an organ independent
process (spontaneous metabolism in the blood stream/interstitium).
-Finally, be aware that most Local Anesthetics work by blocking Na+ channels which prevents depolarization of
the involved neurons. This is the mechanism behind the cessation of pain with anesthetics. Tetrodotoxin is a
poison found in certain foods like pufferfish that blocks Na+ channels. Consuming improperly cooked seafoods
containing this toxin can ultimately lead to death.
The Homunculus
HY Myelination
Note This..
The Motor Pathways can be described as being medial or being lateral.
The Medial Pathways control axial/proximal musculature/posture and balance. These
pathways include;
The Vestibulospinal, Reticulospinal, Tectospinal, and Anterior Corticospinal Tracts.
The Lateral Pathways control distal musculature. These pathways include;
The Lateral Corticospinal and The Rubrospinal Tracts.
These are oversimplifications but theyll do for exam purposes.
-Is involved in the maintenance of posture, balance, muscle tone, and the coordination (NOT INITIATION) of
movement. It is involved in the fine-tuning of skeletal muscle contractions. A good general principle to take
away is that the cerebellum ultimately tries to influence the firing of upper motor neurons in the cerebral
cortex.
-When you look at the cerebellum from the top, you should see an anterior and a posterior lobe.
-When you look at the cerebellum from the bottom, you should be able to see a flocculonodular lobe (which
has multiple connections with the vestibular nuclei, lesions give rise to signs/symptoms of nystagmus and
vertigo) in addition to the anterior/posterior lobes. The flocculonodular lobe of the cerebellum plays an
important role in the vestibulo ocular reflex which will be discussed with the next test.
-Lesions to the lateral hemispheres of the cerebellum tend to present with signs of dysmetria (patient
under/overshoots in the finger to nose test), dysdiadochokinesia (re-that CFM maneuver that requires you to
slap your hands on your thighs rapidly), and intention tremors.
-It is important to contrast the INTENTION TREMORS of cerebellar lesions (tremors show up only when
movement is initiated) with the RESTING TREMORS (tremors show up at rest but disappear with movement)
that are characteristic of Parkinsons Disease.
Cerebellum
Cerebellar Organization/Terminology
-The cerebellum is somewhat organized like the cerebral cortex. There are 3 layers in the cerebellar cortex. A
useful mnemonic is Miles Per Gallon.
-Layer 1 is the molecular cell layer that contains basket cells and stellate cells. This layer also contains the axons
of granule cells which have their cell bodies in a layer that is deeper within the cerebellum. These granule cell
axons are known as parallel fibers.
-Layer 2 is the Purkinje cell layer. These Purkinje cells project from the cerebellar cortex to the deep cerebellar
nuclei. Purkinje cells in the vermis mostly project to the fastigial nucleus. Those in the paravermis area project
to components of the interposed nuclei. Those in the lateral hemispheres project more to the dentate nucleus.
Purkinje cells are inhibitory (GABA).
-Layer 3 is the granular cell layer. These cells project to Purkinje cells and are excitatory (glutamate).
-A key generalization to make is that all neuronal synapses intrinsic to the cerebellum are inhibitory (i.e. use
GABA). The only exceptions are the granule cells which are excitatory. All inputs that are extrinsic to the
cerebellum (climbing and mossy fibers) are for the most part, excitatory.
Cerebellar Organization/Terminology
-Climbing fibers arising from the contralateral inferior olives provide excitatory input to the Purkinje
cells. They also provide excitatory input to the cells of the deep cerebellar nuclei. These fibers serve
more of an error alienating function so that the you make fewer mistakes when you perform a given
motor activity in the future.
-Mossy fibers represent all other sources of input to the cerebellum. If youre lost on your exam with
regards to a given cerebellar input, mossy fiber will probably be the right answer (with the olivary
exception mentioned above). Unlike the climbing fibers, the mossy fibers do not synapse directly on
Purkinje cells. They synapse mostly on deep cerebellar nuclei AND granule cells (which in turn provide
an excitatory input to the cerebellum).
-Is a combined disease that affects both UMN (corticospinal tract) and LMN (anterior horn motor neurons).
UMN symptoms typically include spasticity and exaggerated reflexes. LMN symptoms typically include muscle
fasciculations and wasting.
-It is Super HY to know that there are no sensory symptoms associated with ALS as the dorsal columns are
typically spared. In addition, urinary tract symptoms and visual deficits are rarely, if ever, found in the disease.
As an aside, visual problems that come and go in a female in her 30s-40s should strongly raise your suspicion
for Multiple Sclerosis.
-ALS for the most part shows up in the 40-60 year old age group and is often fatal within 3-5 years.
-The current treatment of choice for ALS is Riluzole which works in a number of mysterious ways that have not
been fully elucidated. It is thought to mostly decrease glutamate release from neurons (remember that
glutamate is excitotoxic, its like taking too much of a good thing) in addition to potentially being an antagonist
at NMDA receptors (which have glutamate as a NT).
-It is also HY to know that certain familial cases of ALS have an association with a Superoxide Dismutase
(SOD1) mutation. Since SOD gobbles up free radicals, a defective functioning of this pathway could potentially
explain the neuron cell death that permeates this process.
Q9-HY Triggers
UMN pathway that decussates in the caudal medulla
Descending motor tract that excites arm flexors
UMN pathway that does not decussate in the caudal medulla
Woman with visual deficits that come and go
Contralateral pain/temp loss + Ipsilateral sensory losses
Nucleus in medulla for upper body proprioceptive information
Nucleus in the medulla for lower body proprioceptive information
Nucleus in the medulla for upper body unconscious proprioception
Afferent cerebellar pathway associated with the SCP
Lesion of the dorsal columns in the spinal cord
Axons of Sensory Information Fibers in the dorsal horn that carry pain/temp
Decussation Point of the Lateral Corticospinal Tract
Decussation Point of the Spinothalamic Tract
Decussation Point of the Rubrospinal Tract
Decussation point of the DCML pathway
Unconscious proprioception for the lower body
Unconscious proprioception for the upper body
Bilateral Loss of pain and temperature sensation
Bilateral Muscle weakness/atrophy with no sensory deficits
Random, asymmetric white matter lesions in a young female
Q10 Key
Bilateral loss of vibratory sense below the level of
the lesion (DCML gone)
Ipsilateral UMN signs below the level of the lesion
(LCST gone)
Introduction/Learning Objectives
-Doing well on the special senses exam depends extensively on understanding mechanisms. You need to
memorize the different pathways and tracts unfortunately, but you also need to understand how to
resolve many of the problems youll meet on the exam.
-There are a few blurry images in this document. I did not mean to include these. However, they do
illustrate certain points extremely well so I left them in. The points I try to get across are very visible
with these images so no worries.
-Make sure you understand THE EYE. It is the most HY special sense for your test.
-Well walk through a host of problems and also spent some good time talking through scenarios that
are relatively HY. Make sure you understand these scenarios/problems which will probably be very well
represented on your test.
-Since this is our last review for the year, well have a short debrief at the end.
Q1
A lesion to the artery at A would most likely result in;
a.
b.
c.
d.
e.
Q1 Key
-The best answer is B, contralateral motor leg/foot deficits.
-The artery indicated by A is the Anterior Cerebral Artery which supplies the
anteromedial cortex. This region corresponds to the leg/foot area in the homunculus.
-The Corticospinal tract decussates in the medullary pyramids so the lesion will give
rise to contralateral motor deficits.
-Another possible correct answer (which is not one of the choices) is a contralateral
leg/foot sensory loss.
Q2
A 72 yo male with a suspected ischemic stroke is rushed to the Med19 clinic by paramedics. A
rapid neuro exam performed on admission reveals total right sided hemiplegia. When asked to
stretch out his tongue, total leftward deviation is noted. Labs obtained 30 minutes after admission
reveal a blood glucose level of 30 mg/dL with rapid correction by the administration of 2g of
dextrose. The patient tells the nurse that the sugar tastes sweet only on one half of his tongue (the
right). The most likely location of the lesion that explains these clinical findings is;
a.
b.
c.
d.
e.
f.
g.
h.
Q2 Key
The best answer is G, the medial medulla on the left.
There is loss of taste sensation on the left (taste sensation ipsilateral).
There is total hemiplegia on the right (remember that this is prior to the pyramidal
decussation, so the lesion has to be on the left).
There is tongue deviation to the left (indicating a hypoglossal nerve lesion on the
ipsilateral side).
The constellation of signs and symptoms points to a lesion in the left medial medulla.
This may seem nitpicky but it is very HY to realize that loss of pain/temperature
sensation essentially localizes lesions to the lateral, not medial brainstem.
Q3
A Med19 student on an Ophthalmology elective performs an eye exam on a 55 yo
female. He notices that shining light in the patients right eye produces no pupillary
response, but shining light in the left eye causes miosis in the right and left eye. The
most likely location of the lesion explaining these clinical findings is;
a.
b.
c.
d.
e.
f.
Q3 Key
The best answer is D, the right optic nerve.
-The loss of all pupillary constriction on the left and the right when light is shone in
the right eye is indicative of an afferent pupillary defect. The restoration of the
pupillary reflex when light is shone in the left eye indicates that the optic nerve on that
side is intact. The absence of miosis in both eyes from light shining in one eye is a very
specific finding in sensory visual deficits.
-A lesion of the oculomotor nerve would present with a lack of miosis of the ipsilateral
eye with light shining in either eye. This finding is very helpful in telling a sensory
from a motor visual deficit.
-Make sure you understand why D is correct. It is very HY.
Q4
A 27 yo Asian male presents to the Careless Clinic with complaints of a 9/10 headache
and blurry vision that has been going for the past 2 hours. A neurological exam reveals
redness in the left eye. The patient recently immigrated to the US from China.
Palpation of the affected eye reveals a rock hard pupil. The Ophthalmology intern
decides to administer a pharmacologic agent to take a closer look at the patients eye. 5
minutes after administration of this agent, the patient reports that he cannot see
anything out of his left eye. The most likely cause of this lesion is;
a.
b.
c.
d.
e.
Q4 Key
The best answer is A, the administration of an adrenergic agonist.
-This patient has closed angle glaucoma.
-The last thing you want to do in a patient with closed angle glaucoma is to administer any agent
that dilates the pupil. This increases intraocular pressure.
-The sympathetic nervous system dilates the pupil. The parasympathetic nervous system
constricts the pupil.
-Administration of a sympathetic agonist (like phenylephrine) or a muscarinic antagonist (like
atropine, tropicamide, cyclopentolate, scopolamine, hyoscyamine, etc)leads to pupillary dilation
(make sure you understand why this is true, more to come in later slides).
-The nicotinic answers are distractors. The control of pupillary constriction/dilation works via
the autonomic, not somatic nervous system.
Ear Introduction
-The outer ear (everything lateral to the tympanic membrane) and the middle ear both contain air. The inner
ear (everything after the oval window) contains fluid.
-The inner ear contains 3 fluid filled chambers with the one on top (scala vestibuli) and the one at the bottom
(scala tympani) both containing a fluid known as perilymph. The one in the middle (the scala media OR
cochlear duct) contains cells bathed in a special extracellular fluid known as endolymph. This endolymph is
made by a specialized epithelium known as the Stria Vascularis.
-Conductive hearing loss occurs in a lesion of any structure in the outer ear (ear wax, etc) or middle ear (otitis
media, otosclerosis, etc-these wear down the ossicles and impair sound amplification).
-Sensorineural hearing loss is a common derivative of lesions in the inner ear. Ototoxic drugs like the
aminoglycosides and platinum compounds like Cisplatin play a huge role here.
-Hyperacusis (usually due to a CN 7 lesion-remember the Stapedius Nerve, a lesion prevents dampening of
incoming sound signals) occurs when theres an increased sensitivity to loud sounds.
-Presbycusis occurs secondary to a loss of hair cells at the base of the cochlea (that control high frequency
hearing). These cells are more fragile and are typically lost first.
Ear Introduction
-The 3 ossicles amplify sound primarily by concentrating the sound
intensity/energy/power over a small area (the foot plate of the stapes). This creates a
sound mechanical advantage.
-The Scala Media (or cochlea duct) is bounded by Reissners membrane on top (which
separates it from the scala vestibuli) AND the apices of the hair cells on the bottom
(which separates it from the scala tympani).
-The hair cells found in the ear/vestibular system lack any sort of regenerative ability.
These cells are the backbone of auditory reception. In addition, a special population of
these cells (outer hair cells) produce little sounds known in medical parlance as
Otoacoustic emissions that are used to determine proper ear function in babies.
Audition-General Mechanism
Step 1-Sound waves from the surroundings vibrate the tympanic membrane.
Step 2-These sound waves are amplified by the 3 bones of the middle ear-the malleus, incus,
and stapes. The stapes vibrates the oval window of the inner ear which is juxtaposed to the
cochlea (which contains a special kind of fluid).
Step 3-These sound vibrations lead to the stimulation of hair cells in the Organ of Corti.
These hair cell fibers (think of them as being like those sensory mechanoreceptors we
discussed for the last test) have a given tonotopy in relation to sound frequency. In other
words, different sound frequencies activate different populations of hair cells. Cells near the
base of the cochlea respond to high frequency sounds while those at the apex respond more
to low frequency sounds. This tonotopic information is represented in the temporal lobe of
the cortex.
Step 4-The generated signals then travel in the cochlea nerve to upper levels in the brain.
-A lesion proximal to the cochlear nucleus will often result in an ipsilateral hearing loss (nothing has crossed
yet).
-However, a lesion distal to the cochlear nucleus will result in bilateral hearing loss since the fibers emanating
from the cochlear nucleus both ascend ipsilaterally and cross at the same time.
-Cochlear implants restore some sort of hearing to individuals that get them (since the neuronal apparatus is
intact). A lesion of any part of the neuronal apparatus makes this essentially impossible.
-It is postulated that high frequency hearing loss occurs first because the hair cells that handle this specific
frequency of sound have a larger SA/V ratio and higher metabolic demands (more ion pumps). With this high
dependence on energy, there is a lower margin of safety if these cells were to undergo any sort of metabolic
stress. This is in contrast to the low frequency hair cells that have a smaller SA/V ratio and lighter metabolic
demands.
-In general, the brain tries to localize sounds by integrating 2 kinds of information from both ears-the loudness
of the sound + the timing of the sound arrival at different parts of the auditory pathway.
-Early intervention in people with hearing loss improves outcomes (in addition to having money/rehab).
Q5
A lesion to the structures at A will result in;
a.
b.
c.
d.
e.
Q5 Key
-The best answer is D, ipsilateral loss of motor movements.
-Remember that the lower motor neurons begin in the ventral horn of the spinal cord.
-B represents the spinothalamic tract fibers.
-C represents the lateral corticospinal tract fibers.
-D represents the fibers of the dorsal column medial lemniscus pathway.
Q6
A 55 yo male comes to the Med19 clinic for his regular 6 month physical. PE reveals a
well appearing man in no acute distress. A review of his current medication list by the
med student on service reveals that the patient takes Nadolol eye drops. The most
likely mechanism of action of this drug is?
a.
b.
c.
d.
e.
Q6 Key
-The best answer is C, the blockade of beta receptors on ciliary epithelium.
-Nadolol is a beta blocker that is used to treat glaucoma. You may not need to know
specific names but you should definitely know that things ending in olol are beta
blockers.
-Beta blockers work by blocking the beta receptors on the ciliary epithelium to prevent
the synthesis of aqueous humor.
Q7
The normal conjugate visual response is shown below. 2 patients (P1/2)present to the Med19 Eye Clinic
and are asked to look to the right during an eye exam. The patients test results are shown in 1 and 2
below. The most likely explanation for these results are?
a.
b.
c.
d.
A lesion of the left oculomotor nerve for P1 and the left CN3 nucleus for P2.
A lesion of the right CN3 nucleus for P1 and the left oculomotor nerve for P2.
A lesion of the left CN6 nucleus for P1 and the left abducens nerve for P2.
A lesion of the right abducens nerve for P1 and the right CN6 nucleus for P2.
Q7 Key
-The best answer is D.
-Patient 1 cannot abduct his right eye on conjugate gaze to the right but can adduct his
left eye.
-Patient 2 cannot abduct his right eye on conjugate gaze to the right. In addition, he
cannot adduct his left eye.
-Patient 1 has a lesion of the abducens nerve (fibers coming after the nucleus). The
Medial Longitudinal Fasciculus (MLF) is still intact.
-Patient 2 has a lesion of the abducens nucleus. Fibers originating in this nucleus
supply CN3 through the MLF so screwing up the nucleus screws up both CN3 and
CN6.
-Make sure this makes sense to you! (more to come in a later slide)
Q8
The normal conjugate visual response is shown below. 2 patients (P3/4)present to the Med19 Eye Clinic and are
asked to look to the right during an eye exam. The patients test results are shown in 3 and 4 below. The most
likely explanation for these results are? (MLF = Medial Longitudinal Fasciculus).
a.
b.
c.
d.
A lesion of the right MLF for P3 and the right cortex for P4.
A lesion of the left MLF for P3 and the left cortex for P4.
A lesion of the right MLF for P3 and the left cortex for P4.
A lesion of the left MLF for P3 and the right cortex for P4.
Q8 Key
-The best answer is B.
-Patient 3 can abduct his right eye but cannot adduct his left eye.
-Patient 4 cannot abduct his right or adduct his left eye.
-Patient 3 has a lesion of the left MLF. Remember that the left MLF controls the movement of the
ipsilateral CN3 in response to stimulation from the right CN6 nucleus. If the patient had an actual
CN3 lesion, he would have a down and out eye on the ipsilateral side, which he does not.
-Patient 4 has a lesion of the cortex on the left. Remember that the left frontal eye field projects to the
right Paramedian Pontine Reticular Formation (PPRF) which is in very close proximity to the CN6
nucleus. The right PPRF then controls the ipsilateral LR muscle and the contralateral MR muscle to
cause right conjugate gaze.
-As an added question, is there another kind of lesion that would produce the same visual deficits as that
observed in Patient 4?
Vestibular Diseases
-Menieres Disease is primarily caused by issues with flow, production, or obstruction of endolymph in
the vestibular system.
-If you see this cluster on your exam-Vertigo, Tinnitus (ringing from a mix of endolymph with
perilymph), and Hearing loss (that is transient), stop thinking, and pick Menieres as your answer.
-There are lots of treatment options but a HY one to be aware of is Gentamicin. This is an example of
using a known side effect of a drug (ototoxicity-hello aminoglycosides!), to treat a medical problem.
Since the vestibular system misbehaves in Menieres, one strategy is to essentially destroy it. The only
issue is the fact that hair cells exist in other places besides the vestibular system (like the ears), so
sensorineural hearing loss could be an unwelcome side effect.
-Vertigo is another common disease associated with the vestibular system where the world seems to
bounce around in ones field of view. This is typically associated with severe nausea and vomiting.
Q9
A 66yo female who was a recent victim of a stroke presents to the Med19 clinic for
follow up after hospital discharge. A thorough exam reveals an absent gag reflex.
Further neurologic examination would most likely reveal;
a.
b.
c.
d.
e.
Q9 Key
-A patient with an absent gag reflex has 1 of 2 cranial nerve lesions-CN9
(Glossopharyngeal) or CN10 (Vagus). CN9 is the afferent limb of the gag reflex. CN10
is the efferent limb of the gag reflex.
-Therefore, you should immediately guide your thoughts towards anything remotely
resembling lesions of any of these nerves.
-The only option that fits is a loss of sensation (which could be general sense or taste)
in the posterior third of the tongue which is controlled by CN 9.
-Hence C is the best answer. Please do not fall for the tongue deviation distractor.
That is CN12 (hypoglossal) territory.
Q10
A 65 yo man undergoes synchronized cardioversion for the emergent treatment of new
onset atrial fibrillation. Neurologic exam 3 days after the procedure reveals a left lower
quadrantanopia. This deficit is most likely associated with embolic occlusion of a vessel
supplying the;
a.
b.
c.
d.
e.
Q10 Key
-The best answer here is E.
-A loss of vision in the inferior visual field means there is a superior lesion
somewhere.
-A loss in the left visual field means that there is a lesion in the right optic radiations.
-Remember that the information for the inferior visual field travels superiorly in the
cortex through the parietal lobe (Baums Loop).
-It is also noteworthy to remember that information from the superior visual field
travels inferiorly in the cortex through the temporal lobe (Meyers Loop).
Q11
A 23 yo female with a history of severe autoimmune disease presents to the Med19
clinic for a workup of new neurological complaints. PE reveals ptosis in the left eye.
Further examination reveals a massively dilated and unreactive pupil (to light). These
findings are best explained by a lesion to the?
a.
b.
c.
d.
e.
Facial Nucleus
Facial Nerve
Superior Cervical Ganglion
Ciliary Ganglion
Trigeminal Nerve
Q11 Key
-The best answer is D.
-A pupil that is unreactive to light in the setting of mydriasis is quite concerning for an
oculomotor nerve lesion. CN 3 mediates miosis and the efferent limb of the pupillary
light reflex.
-The other answers make absolutely no sense at all.
Q12
Match the visual field defect to the appropriate letters;
Loss of vision in the right visual field for the left eye.
Loss of contralateral superior visual field information.
Loss of the left visual field in the left eye AND the right visual field in the right eye.
Q12 Key
Match the visual field defect to the appropriate letters;
Loss of vision in the right visual field for the left eye-C
Loss of contralateral superior visual field information-E
Loss of the left visual field in the left eye AND the right visual field in the right eye-B
The ANS and The Eye (Note the 2 Distinct Muscle Types)
Glaucoma Pathophysiology
-Glaucoma is defined as an increase in Intraocular Pressure (IOP) secondary to an imbalance b/w
aqueous humor production and drainage. The increased IOP (in a closed box like the eye),
squishes most of the vasculature that supplies the retina/optic nerve which can ultimately lead to
blindness. It is HY to know that peripheral vision is typically lost first in the setting of glaucoma.
-There are 2 types of glaucoma.
-Open Angle Glaucoma is glaucoma that arises secondary to decreased drainage of aqueous
humor from the anterior chamber in the presence of a grossly normal angle b/w the iris and
cornea. OAG is a painless, chronic condition.
-Closed Angle Glaucoma is glaucoma that arises secondary to a bunching up of the iris against
the cornea which essentially closes out the angle that leads into the trabecular meshwork. This
leads to a very rapid buildup of aqueous humor in the anterior/posterior chambers with a
concomitant increase in IOP. CAG is a painful, acute condition. This is a medical emergency and
must be treated rapidly to prevent impending blindness.
Glaucoma Pathophysiology
-The IOP is measured by tonometry (puff of air into the eyes if youve ever visited an
ophthalmologist).
-It is important to understand for reasons that will be discussed shortly that drugs that dilate the
eye are contraindicated in closed angle glaucoma. Mydriasis is not something youd want to
trigger in a closed angle situation.
-Glaucoma is more common in older people, African Americans, and individuals with a family
history of the disease.
-Glaucoma has a strong association with a high cup/disc ratio (normal is less than 0.3). An
increasing cup to disk ratio means that more optic nerve fibers are dying. This increases the
amount of space in the disk which manifests as the increased ratio. A good way to think about this
is a donut being the disk and the donut hole being the cup. If you keep eating a donut from the
center (death of optic nerve fibers), the donut hole gets bigger (cup/disc ratio goes up).
Anosmia
-Just like we have conductive and sensorineural hearing loss, theres also conductive
(odorants cant hit the receptors on the Olfactory Receptor Neurons) and
sensorineural (problems with the pathways to the brain) anosmia.
-Conductive anosmia is typically associated with traumatic/inflammatory nasal
exposures (i.e. the unfortunate contact b/w an enemys fist and an individuals face,
nasal polyps, etc).
-Injuries to the head (i.e. cribriform plate fracture-this is a classic exam scenario) and
neurodegenerative diseases like Alzheimers and Parkinsons can lead to neuronal
death which can trigger a sensorineural anosmia.
Taste-A Summary/Lesions
Like many sensory pathways, the taste pathway is a 3 neuron pathway.
There are receptor cells in taste buds that sense taste information. Through chemical synapses
they relay to;
Neuron 1-which are fibers of CN 5/7/9/10. These relay to;
Neuron 2-which are neurons with cell bodies in the rostral solitary nucleus of the medulla (note
that respiratory/cardiac centers are in this general area). Unlike other Neuron 2s, these fibers
do not cross. Hence, lesions along this pathway result in an ipsilateral loss of taste sensation.
These fibers then relay to;
Neuron 3-which are neurons with cell bodies in the VPM nucleus of the thalamus. These
ultimately project to the insula/frontal operculum of the cerebral cortex.
N/B-a lesion along the taste pathway leads to a contralateral heightened unpleasant sensation (to
this day, this makes no logical sense to me. Sorry)
Metabolic Disorders-Hyponatremia/CPM
-Hyponatremia (low levels of plasma Na) is an electrolyte abnormality that is caused by a whole host of
metabolic disorders (more to come in GTS Renal).
-Hyponatremia causes a lot of bad things (particularly seizures).
-However, the key thing to know for Neuro (and for future exams) is that treating hyponatremia too quickly
can cause a condition known as Central Pontine Myelinolysis/Osmotic Demyelination Syndrome. Exposing an
individual with severe hyponatremia to hypertonic solutions over a short period of time leads to massive
neuronal shrinkage (since water is being drawn out) and devastating demyelination.
-The extensive demyelination shuts off most of the brain stem. Individuals with this condition have total
quadriplegia with the only residual sensory/motor function being eye movements. This is known as locked in
syndrome.
-A very useful FA mnemonic is from low to high, your pons will die AND from high to low, your brain will
blow (for hypernatremia).
-In general, it is not a good idea to correct an electrolyte disturbance too quickly.
HY Epidemiology Review
Some MS2
Few Words
Why should you care about Epidemiology?
-Be able to deal with scientific literature intelligently.
-Learn how to think logically.
-Pass the test.
-Tested heavily on the boards.
-Is important for clinical decision making.
-Doing well in Epi depends primarily on having the right thought process in problem
solving, not memorizing equations.
Q1
A town has a population of 18,000 people. Of these, 3600 have incurable diabetes.
There are 300 new cases and 50 deaths each year from diabetes. There are 75 deaths
per year from all causes. The prevalence of diabetes in this town is given by?
a.
b.
c.
d.
e.
300/3600
3600/18000
50/3600
75/18000
425/18000
Q1 Key
The answer is B.
Remember,
Prevalence = Total # of cases/# of people in the population that are not dead
In the Q, there are 3600 people with the disease and 18000 people in the population at
the time, so the prevalence is 3600/18000 which is answer B.
Note that the Proportionate mortality ratio in this case will be 50/75 * 1000 or 670 per
1000 deaths.
And Case Fatality rate = 50/3600.
Q2
Given the chart below of a group of competitive athletes (indicating a sample of 10 individuals with restrictive cardiomyopathyRCM);
a.
b.
c.
Q2 Key
For Part A,
In 2010, there were 5 new cases of RCM. Of the 10 people in the population, 1 was
dead already, and the other already had the disease (so he lacked the potential to be a
new case.
Remember, Incidence = # of new cases/# at risk to be a new case
Therefore, the incidence of RCM in 2010 is .
The prevalence of RCM in 2011 is 5/7.
The point prevalence of RCM on January 1 2012 is 4/6.
Q3 Key
-Prevalence goes down, but not incidence (decreased duration).
-Prevalence and Incidence both go down (fewer new cases and
hence fewer people having the disease).
-Prevalence increases, but there is no change to incidence
(increased duration).
-Note that incidence approximates prevalence with a short
disease duration.
Q4
A new urine test to detect the presence of HIV was given to 1000 patients. Although
200 of the patients were actually infected with the virus, the test was positive in only
160 of the 200 patient population. Of the 800 patients who were not infected, the test
was negative in 720 patients and positive in 80 patients. Using the information above,
calculate the;
a.
b.
c.
d.
e.
Sensitivity
Specificity
PPV
NPV and;
The prevalence of HIV in this population.
Q4 Key
Q5
A 60 year old man visits his primary care physician with complaints of urinary
frequency. Examination finds a 2 cm nodule on his prostate gland. The concerned
physician orders a Prostate Specific Antigen (PSA) serum test. By common standard, a
PSA level greater than 4 ng/ml is considered abnormal. Using this standard, the test
has a sensitivity of 90% and a specificity of 80%. A recently published epidemiologic
article found that in a cross sectional study, 20% of men in this age group have
prostate cancer. The result on the patient's PSA is 8 ng/ml. What is your best estimate
of the likelihood that this man actually has prostate cancer?
Q6
What is the incidence of Disease X in as defined by the following 2 by 2 table?
What is the prevalence of Disease X as defined by the following 2 by 2 table?
Q6 Key
-There is no incidence data that can be derived
from the table (why?)
-The prevalence of Disease X in the population is
50%.
Q7
In a particularly bad year, the total number of cases of Disease X referenced in the
previous question increases to a new high of 500, 000 people. Which of the following
statements are false?
a. The ratio of individuals detected by the test to be disease free out of the total
number of healthy people increases.
b. The likelihood of a negative test result being true increases.
c. The ratio of individuals detected by the test to be with disease out of the total
number of diseased people decreases.
d. The likelihood of a positive test result being true increases.
e. The likelihood of a negative test result being true decreases.
f. The likelihood of a positive test result being true decreases.
Q8
Pick the points on the distribution below that correspond to the highest sensitivity,
specificity, NPV, and PPV.
Q8
Highest sensitivity is E
Highest specificity is C
Highest PPV is C
Highest NPV is E
-At the point of highest sensitivity, NPV is at a maximum.
-At the point of highest specificity, PPV is at a maximum.
-Memory Tool (The Ns and Ps match).
Q9
Which of the following points on the curve represents the best screening test?
Q9 Key
The best answer is Curve 6
ROC curves (are HY!). Curve 6 has the highest sensitivity, and
also highest specificity (because 1-specificity is at a minimum).
Other Takeaways
Q10
A study is designed to determine the relationship between high intracranial pressures
and peptic ulcers. To accomplish this, researchers used hospital records of patients
diagnosed with peptic ulcer disease and patients diagnosed with other disorders over
the period of December 2011-December 2014. The intracranial pressures upon
admission of these patients was determined from these records. Which of the following
should be included in the analysis of information from this study?
a.
b.
c.
d.
e.
Relative risk
Incidence
Odds Ratio
Prevalence
Absolute Risk
Q10 KEY
-This is a case control study (retrospective)
-It starts with outcomes and goes back to look at exposures.
-The only major piece of information derived from a Case Control Study is an Odds
Ratio.
-Incidence/Prevalence data cannot be determined from a CC study (why?).
-It is particularly good at detecting risk factors for a given disease (especially rare
diseases).
-Hence the best answer is C.
Q11
A study is performed to determine the effectiveness of Montelukast, a leukotriene
receptor antagonist designed to treat asthma. To do this, 25 allergic patients are
assigned to one of two groups, the Montelukast group (13 patients) or a Placebo (12
patients). The patients are then followed over a 6 month period. This study is best
described as a;
a.
b.
c.
d.
Cohort study.
Cross Sectional Study.
Case Control study.
Clinical Trial.
Q11
A study is performed to determine the effectiveness of Montelukast, a leukotriene
receptor antagonist designed to treat asthma. To do this, 25 allergic patients are
assigned to one of two groups, the Montelukast group (13 patients) or a Placebo (12
patients). The patients are then followed over a 6 month period. This study is best
described as a;
a.
b.
c.
d.
Cohort study.
Cross Sectional Study.
Case Control study.
Clinical Trial.
Q12
In a suburb of Baltimore, it was reported that there were 300 Hep B positive
individuals, of whom 10 died in 2012. The case fatality rate per 100 people is;
a.
b.
c.
d.
e.
0.33%
3%
3.3%
3.5%
33%
Q12
In a suburb of Baltimore, it was reported that there were 300 Hep B positive
individuals, of whom 10 died in 2012. The case fatality rate per 100 people is;
a.
b.
c.
d.
e.
0.33%
3%
3.3%
3.5%
33%
Why?
Case Fatality Rate simply refers to the proportion of people with a given disease who
die over a defined time period.
Remember the general principle of creating a ratio in Epidemiology by multiplying by
some # (typically a multiple of 10)
In Q12, CFR = 10 dead/300 people with Hep B * 100 = 3.3%
Q13
In the Hopkins class of 120 medical students, the mean systolic blood pressure was
found to be 126 mm Hg with a SD of 6 mm Hg. If the blood pressures in this sample
are normally distributed, what portion of the medical students will have systolic blood
pressures above 132 mm Hg?
a.
b.
c.
d.
e.
2.5%
0.5%
5%
16%
32%
Q13
In the Hopkins class of 120 medical students, the mean systolic blood pressure was
found to be 126 mm Hg with a SD of 6 mm Hg. If the blood pressures in this sample
are normally distributed, what portion of the medical students will have systolic blood
pressures above 132 mm Hg?
a.
b.
c.
d.
e.
2.5%
0.5%
5%
16%
32%
Standard Curves
-For a normal distribution the mean = median = mode.
-For a right skewed curve, the tail is on the right and from the tail go in alphabetical
order (mean, median, mode). In other words, the mean is the highest value. Reverse all
of these for left skews.
-A fat normal curve has a high SD, while a thin normal curve has a small SD.
-68-95-99.7 rule (applies to 1, 2, 3 SD around the mean)
-In Q13, 1 SD above the mean is 132 mm Hg, so 50% + 34% of the class lie below that
cut off, leaving 16% unaccounted for.
Q14
In a cohort study examining the relationship between the use of exogenous estrogens
and the subsequent risk of breast cancer, a sample of 1000 premenopausal women
were followed for 8 years. The results are presented in the table below. The relative risk
associated with estrogen therapy in this study is?
a.
b.
c.
d.
e.
0.25
0.33
0.5
2
3
Q14
In a cohort study examining the relationship between the use of exogenous estrogens
and the subsequent risk of breast cancer, a sample of 1000 premenopausal women
were followed for 8 years. The results are presented in the table below. The relative risk
associated with estrogen therapy in this study is?
a.
b.
c.
d.
e.
0.25
0.33
0.5
2
3
Relative Risk
-Is simply a ratio of incidence.
-Is the typical outgrowth of a Cohort Study (because we have incidence information)
-Can a relative risk be calculated for a Case Control Study?
-In Q14, 60% of people who took estrogen got BRCA, 20% of individuals who did not
take estrogen got BRCA. Hence the ratio of incidences is 60%/20% = 3
-Be able to interpret the results of these studies in words (i.e. statements explaining
your findings)!
Q15
Serum homocysteine levels for 2 groups of Americans were recorded in 2012. The
mean homocysteine level for a group of 28 African Americans was 271 mg/dL and 184
mg/dL for a group of 28 Asian Americans. To determine if these results were
significantly different, a Med19 student performed a statistical test as part of his SC
project. Which of the following tests was most likely used by the student in his
analysis?
a.
b.
c.
d.
e.
Q15
Serum homocysteine levels for 2 groups of Americans were recorded in 2012. The
mean homocysteine level for a group of 28 African Americans was 271 mg/dL and 184
mg/dL for a group of 28 Asian Americans. To determine if these results were
significantly different, a Med19 student performed a statistical test as part of his SC
project. Which of the following tests was most likely used by the student in his
analysis?
a.
b.
c.
d.
e.
Q16
In a prospective study, the occurrence of Peptic Ulcer Disease was recorded for
smokers and nonsmokers. The difference in incidence between smokers and
nonsmokers was reported to be significant at the p<0.05 level. The most appropriate
statement that can be made about this study is that;
a. The null hypothesis may be rejected even though the results could have occurred
purely by chance a maximum of 5% of the time.
b. The null hypothesis may be accepted because there is a difference in the incidence
rates between smokers and nonsmokers only 5% of the time.
c. A causal relationship between smoking and the incidence of Peptic Ulcer Disease
may be established at a significance level of 0.05.
Q16
In a prospective study, the occurrence of Peptic Ulcer Disease was recorded for
smokers and nonsmokers. The difference in incidence between smokers and
nonsmokers was reported to be significant at the p<0.05 level. The most appropriate
statement that can be made about this study is that;
a. The null hypothesis may be rejected even though the results could have occurred
purely by chance a maximum of 5% of the time.
b. The null hypothesis may be accepted because there is a difference in the incidence
rates between smokers and nonsmokers only 5% of the time.
c. A causal relationship between smoking and the incidence of Peptic Ulcer Disease
may be established at a significance level of 0.05.
P-Value
-Reflects the probability that the results obtained from a test could have occurred by
chance.
-Think of it as a bar you never want to cross. As long as you stay below the bar, you can
reject the null and fail to reject the alternative hypothesis (and vice versa).
Q17
In a study concerning the relationship between phenylbutazone and the subsequent
risk of neutropenia, medical records of 300 children were investigated with the results
shown in the table below. What is the odds ratio in this study?
a.
b.
c.
d.
e.
3.29
2.29
5.67
3.23
7.16
Q17
In a study concerning the relationship between phenylbutazone and the subsequent
risk of neutropenia, medical records of 300 children were investigated with the results
shown in the table below. What is the odds ratio in this study?
a.
b.
c.
d.
e.
3.29
2.29
5.67
3.23
7.16
Odds Ratios
-Are the derivatives of Case Control Studies.
-When does an Odds Ratio approximate the relative risk?
-Compares the odds of a case of a disease being exposed to a given risk factor to the
odds of controls being exposed to the same risk factor (it makes sense that the odds of
exposure in a diseased case should be higher than the odds of exposure in a control
case).
-Easy calculation (The Logical People Product)/(The Weird People Product)
-Logical people (exposed and affected, not exposed and unaffected). Weird people
(exposed and unaffected, not exposed and affected).
Q18
What kinds of errors/right decisions are made given the following scenarios?
-Rejecting the null hypothesis when the null hypothesis is false?
-Accepting the null hypothesis when the null hypothesis is false?
-Rejecting the null hypothesis when the null hypothesis is true?
-Accepting the null hypothesis when the null hypothesis is true?
Q18
What kinds of errors/right decisions are made given the following scenarios?
-Rejecting the null hypothesis when the null hypothesis is false?-Correct
-Accepting the null hypothesis when the null hypothesis is false?-Type 2 Error
-Rejecting the null hypothesis when the null hypothesis is true?-Type 1 Error
-Accepting the null hypothesis when the null hypothesis is true?-Correct
Note that the Type 1 error is the Alpha error (P-Value), while the Type 2 Error is the
Beta error (1-Power). How could you increase the power of an experiment?
Types of Errors
Q19
A standardized test was used to assess the level of happiness among Hopkins medical
students. The results yielded a mean of 17.60 with confidence limits of 17.55 and 17.65.
This presented confidence limit is;
a.
b.
c.
d.
e.
Less precise, but has a higher confidence than 17.20 and 18.00
More precise, but has a lower confidence than 17.20 and 18.00
Less precise, but has a lower confidence than 17.20 and 18.00
More precise, but has a higher confidence than 17.20 and 18.00
Cannot be determined from the information given.
Q19
A standardized test was used to assess the level of happiness among Hopkins medical
students. The results yielded a mean of 17.60 with confidence limits of 17.55 and 17.65.
This presented confidence limit is;
a.
b.
c.
d.
e.
Less precise, but has a higher confidence than 17.20 and 18.00
More precise, but has a lower confidence than 17.20 and 18.00
Less precise, but has a lower confidence than 17.20 and 18.00
More precise, but has a higher confidence than 17.20 and 18.00
Cannot be determined from the information given.
Confidence Intervals
-Tighter confidence intervals have less room for error so you should be less confident
in them.
-Tighter confidence intervals are more precise because they have lower standard
deviations.
Q20
The mean blood glucose level of a sample of 81 patients taken from MGH was 170
mg/dL with a standard deviation of 15 mg/dL. Compute the 95% confidence interval
and in words interpret your results.
Q20
Mean = 170 mg/dL
Standard Error of the Mean = 15/sq. rt of 81 = 1.67 mg/dL
Z-Score for 95% Confidence Interval = 2 (1.96 for the ethically minded).
CI 170 +/- (2*1.67) = 170 +/- 3.34.
You can say with 95% confidence that the real mean blood pressure of the MGH
population falls between 166.66 and 173.34 mg/dL
Q21
4 separate drug trials were conducted to test the relative effectiveness of 4 different 3-Beta Hydroxysteroid DH agonists as a
means of increasing Testosterone levels in impotent males. The mean testosterone levels in the study with confidence intervals
(solid lines) are graphed below. Use the graph to determine if the following statements are true or false.
a.
b.
c.
d.
Q21 Key
Statements A, B, and D are true.
The general principle is this-when 2 confidence intervals cross each other, there is no
difference between those treatments. Dont be surprised by an exam scenario that
presents multiple, but similar tests with multiple confidence intervals asking you to
evaluate the relative effectiveness (or efficacy) of some kind of intervention.
Q22
The table below shows the results of 4 different cohort studies that were handed to a Med19 student by his SC
mentor trying to test his knowledge of Biostatistics. He asks the student to interpret the results using the
following 2 parameters;
a.
b.
Q22
-A relative risk is a ratio of incidence rates.
-With similar incidence rates, the ratio (or RR) should be 1.
-Confidence intervals crossing the 1 boundary indicate similarities in incidence
between exposed and unexposed groups. The same rule obtains for Odds Ratios.
-Therefore, Comparisons B and C do not have significant results.
-However, comparison A shows significant results with a 134% increased risk and D
shows significant results with a 27% decreased risk.
-For measurements involving differences, the CI boundary should not cross zero. If it
does, the results are NOT significant.
Q23
During the 2nd look weekend, a barbecue was organized at the beginning of the year to welcome the new
Med19 class. The total number of people in attendance was 100 including the Med19 class and a few others.
Fried chicken, sandwiches, and potato salads were served. The following day, 28 of the attendees had diarrhea
and vomiting. All the attendees were questioned about what they had eaten, and the following table was
obtained. Which of the following best describes the attack rate among all of the attendees who had potato salad?
a.
b.
c.
d.
e.
11%
20%
28%
34%
47%
Q23
The attack rate is 34% (will solve in session)
Q24
Q24
Mode for Females- Zero sexual partners
Mode for Males- 1 sexual partner
Q25
Q25
Median for Males-1 sexual partner
Median for Females- 1 sexual partner
CRANIAL CAVITY
Key Definitions
Periosteal Dura-closely attached to the skull via sutures.
Dural Venous Sinuses-Formed from the few points of separation b/w the Periosteal
and Meningeal Dura (no valves unlike many other venous structures in the body)
Meningeal Dura Duplications/Folds-forms the Tentorium Cerebelli (separates
what?), Falx Cerebri (separates what?), Falx Cerebelli (separates what?) and
Diaphragma Sellae (Roof of?)
CSF is found in??
CSF DRAINAGE/CIRCULATION
CIRCLE OF WILLIS
CIRCLE OF WILLIS
Hematomas
Epidural Hematomas
-Between the Dura and the Skull (explains the Lens Shape)
-Middle Meningeal Artery rupture (branch of? branch of? branch of? branch of?)
-Higher Pressure (medical emergency)
-Classic Lucid Interval
-Eventual Herniation (This is Bad!!!)
-Does NOT cross suture lines (b/c the periosteal dura is attached to the skull)
Subdural Hematoma
Subdural Hematomas
-Between the Dura and Arachnoid
-Bridging Vein (starts from cortex/pierces meninges/drains into dural venous sinuses)
Tear-Rapid Acceleration/Deceleration
-Lower Pressure (longer lead time before bad stuff happens)
-Gradual Increase in Headache/Confusion
-Common in old people
-Crescent Shaped
-CROSSES suture lines (Re-Meningeal Dura is not suture bound)
Subarachnoid Hemorrhage
Subarachnoid Hemorrhage
-Between the Arachnoid/Pia
-Shaped like a Spider
-Rupture of a berry aneurysm (ACA most common)
-Classic Q Stem (Worst Headache of My Life)
Keep In Mind
PHARYNGEAL POUCHES-ENDODERM
Keep In Mind-Pouches
-Theres a more caudal migration of 3 relative to 4 (explains the weird contrasting
origins of the IPG from Pouch 3 and the SPG from Pouch 4). Structure formation
depends on NCC.
-Ventral midline endodermal evagination-downgrowth (Thyroglossal Duct, should
fuse and disappear)-Ballooning at the tail (Thyroid gland)..... This is a common theme
in Embryology (e. g. Lungs)
CYSTS
Lateral Cervical Cyst-Incomplete filling of the
remaining pouches by Cleft/Arch 2, (embryonic
derivative-ectoderm). Overlying Superficial Neck
Muscle? Cranial Nerve?
Medial/Thyroglossal Duct Cyst-failed fusion/disappearance of
the Thyroglossal Duct, (embryonic derivative-endoderm)
CLINICAL CONSIDERATIONS
1. Down's Syndrome (Constellation of Symptoms,
failed NCC migration)-Cleft Lip/palate,
Hirschsprung Disease , Congenital Heart
Defects, Misshapen teeth etc.
2. 3rd/4th Pouch Disease-No thymic shadow on
CXR, Susceptibility to Infection, Hypocalcemia
(Why?)
Keep In Mind
For each arch, try knowing the following;
-Nerves
-Arteries
-If you know the nerves, youll know the muscles
-Muscles (mesoderm)
-Neural Crest Cells (ultimately ectoderm, bones, cartilage, and ligaments)
CN1-OLFACTORY
-Starts as Fila Olfactoria
-Enters through the Cribriform Plate
-Synapses at The Olfactory Bulbs
-Carries the sense of smell
-A cribriform plate fracture leads to Anosmia
CN2-OPTIC
-Coalition of Retinal Ganglion Cells
-Traverses Optic Canal (with Ophthalmic Artery)
-Optic Nerve (Proximal), Optic Chiasm (runs above what structure?), Optic Tract (Distal), Associated
Thalamic Nucleus?, Info relayed to?
-Pituitary tumors (Adenomas/Craniopharyngiomas) cause VF defects
-Afferent limb of the pupillary light reflex
-Affected in MS (is a true CNS tract)
-Fibers go to The Lateral Geniculate Nucleus of the Thalamus/Visual Cortex in the Occipital Lobes (Calcarine
Sulcus)
LESIONS
If you lesion the Optic Nerve-One Eye Gone
If you lesion the Optic Chiasm-Tunnel Vision
If you lesion the Optic Tract-Lose the contralateral
visual field
CN3-OCULOMOTOR
-Edinger Westphal Nucleus (PSNS)/Oculomotor Nucleus (Skeletal Motor)Interpeduncular Fossa (of midbrain)-Passes b/w SCA/PCA-Cavernous Sinus-Superior
Orbital Fissure
-Innervates SR (Up), IR (Down), IO (Up and Out), MR (Adducts), LPS (Elevates)-all
skeletal muscle
-PSNS (Ciliary mm., Pupillary Sphincters)
-CN3 palsy (Down and Out)
-Uncal Relationship-affected by an ICP increase
LESIONS
-Complete lesion-Down and Out Eye/External Strabismus (Unopposed LR/SO)
-Ptosis/Droopy eyelid (LPS)
-Blown Pupil (Unopposed Sympathetic Activity)
-Loss of the Accommodation and Pupillary Light Reflex
-Diplopia/Double Vision
-Diabetes-Ischemia-Lose Somatic Nerve Function-Inner Fibers
-Aneurysms-Lose Parasympathetic Function-Outer Fibers
CN4-TROCHLEAR
-Midbrain
-Arises from the dorsal aspect of the midbrain below the inferior colliculus
-Fibers cross (only CN that gives contralateral findings in the setting of a lesion
-Cavernous Sinus-Superior Orbital Fissure
-Innervates SO4 (Down and Out)
-Lesions (problems w/reading, going downstairs)
-Head deviates Superomedially to correct deficit (away from the lesioned side)
PATHWAY
CN5-UNCLE TRIGEMINAL
-Pons
-3 branches (V1-Opthalmic (SOF), V2-Maxillary (FR), V3-Mandibular (FO))
-Muscles of Mastication (V3)
-Jaw closers (MTM)-Masseter, Temporalis, Medial Pterygoids
-Jaw Openers-Lateral Pterygoids
-Anterior belly of digastric, mylohyoid, tensor tympani, tensor veli palatini
-General Sensation from Anterior of tongue (V3)
CN5-CONTD
-Ophthalmic (Sensation from forehead, scalp, cornea, lesion includes loss of blink
reflex). Branches-Nasociliary/Frontal/Lacrimal Nerves.
-Maxillary (Sensation from Palate, Nasal Cavity, Face/Teeth associated with the
Maxilla)
-Mandibular-lower jaw and muscles of mastication. General sensation from Anterior
of tongue. Mylohyoid, Anterior Belly of The Digastric, Tensor Tympani, Tensor Veli
Palatini.
TRIGEMINAL SENSATION
PTERYGOPALATINE FOSSA
-Anterior/Superior communication w/the orbit (via Inferior Orbital Fissure)
-Lateral communication w/the Infratemporal Fossa (via Pterygomaxillary Fissure)
-Medial Communication w/the Nasal Cavity (via Sphenopalatine Foramen-transmits
SP Artery/Vein, Nasopalatine branch of V2)
-Posterior communication w/the Middle Cranial Fossa/skull base (via Foramen
Rotundum, Pterygoid Canal, Palato-Vaginal Canal)
-Downward communication w/the Oral Cavity (via Greater Palatine Canal)
PTERYGOPALATINE GANGLION
CN6-ABDUCENS
-Pons
-Cavernous Sinus (Medial)-Superior Orbital Fissure
-Innervates LR (Abduction)
-Lesion produces internal strabismus
CN7-FACIAL
-Pons
-Internal Acoustic Meatus-Facial Canal (petrous part of Temporal Bone)-Parotid Gland-Stylomastoid Foramen
-Ten Zulus Bit My Chin (Temporal, Zygomatic, Buccal, Marginal Mandibular, Cervical)
-Cuts through the Parotid, but does not innervate it. Exits via The Stylomastoid Foramen
-Muscles of Facial Expression, Stylohyoid, Stapedius, Posterior Belly of The Digastric, Orbicularis Oculi/Oris.
-Taste (not general sensation, Anterior tongue)
-Lesions (Bells Palsy)
-Sensory Innervation of the Hard/Soft Palates/some parts of the outer ear
CN7-CONTD
-N/B Chorda Tympani exits the skull via The Petrotympanic Fissure
-Saliva Production (Sublingual, Submandibular Glands) via Chorda Tympani
-Tears (its ok to do this sometimes)-Lacrimal Glands via Chorda Tympani
-Mucus Production (Nasal, Palatine glands)
-Hyperacusis (stapedius lesion-sound oversensitivity), Reduced Secretions.
CN8-VESTIBULOCOCHLEAR
-Pons, Internal Acoustic Meatus
-Audition/Balance
-Acoustic Neuromas, Vertigo, Hearing Loss, Nystagmus
-Medial Geniculate Nucleus (Music)
CN9-GLOSSOPHARYNGEAL
-Medulla, Jugular Foramen
-Carotid Body/Sinus (Chemo/Baroreceptors)
-Taste/General Sensation from Posterior of tongue
-Stylopharyngeus Muscle
-Parotid Gland (via the Otic Ganglion-source of postganglionic parasympathetics)
(remember!-CN 7 cuts through but does not innervate!)
-Sensory limb of the gag reflex
-Sensation from Upper Pharynx, Tonsils, External Ear
CN10-VAGUS
-Medulla, Jugular Foramen
-Up to The Splenic Flexure
-Most thoracic/abdominal viscera
-Aortic Arch/Aortic Bodies (Chemo/Baroreceptors)-dont confuse w/Carotid Body/Sinus from CN 9.
-Pharynx/Larynx
-Tongue Muscle (palatoglossus)
-Motor limb of the gag reflex
CN10-CONTD
-Innervates all muscles of the palate except Tensor Palatini
-Innervates all muscles of the pharynx except Stylopharyngeus
-Innervates the muscles of the larynx (Recurrent Laryngeal Nerve-except
Cricothyroid), trachea, and esophagus
-Lesions (Uvula Deviation, Dysphagia, Hoarseness)
-In the neck, CN 10 traverses the carotid sheath posterior to the ICA, and medial to the
IJV
CN11-ACCESSORY
-Misplaced Spinal Nerve (C1-C6)
-Enters through the Foramen Magnum
-Exits through the Jugular Foramen
-Trapezius, Sternocleidomastoid
-Lesions (shoulder droop on affected side, inability to turn head away from affected
side, I cant comb my hair)
CN12-HYPOGLOSSAL
-Medulla, Hypoglossal Canal
-Extrinsic tongue muscles (Genioglossus, Hyoglossus, Styloglossus, and Palatoglossuscareful here!)
-All intrinsic/extrinsic tongue muscles except?
-Lesions (tongue deviates towards the side of the lesion-lick your wounds)
GO DOMINATE!
HY Heme Review
Some MS2
Objectives/Suggestions
-Hematology is unfortunately one of those blocks where much of the information is HY and applicable to the exam and
future exams.
-On a good note, Heme relies heavily on mechanistic thinking and less on memorization.
-There are 3 key principles behind learning and doing well in Heme.. The first is to rationalize every fact you learn. This
will severely cut down on what you need to memorize and also make question answering more successful. Secondly,
group things into neat boxes in your mind based on one key, overarching characteristic and then find 1-2 key things that
could help to distinguish between the different members of each little block. For example, the very first thing you
should do in any MCV < 80 question on your exam is to stare at the Ferritin levels. Finally, engage in practice drills to
apply what you know to problems. Try to explain mechanisms to yourself or a friend as added reinforcement.
-Accomplishing the 3 goals above is the key focus of this presentation.
-As mentioned in previous sessions, find a way to encode this information into an abbreviated format that can be
reviewed periodically. Subsequent reviews will take a much shorter time than the initial review.
-Theres a fair amount of repetition/redundancy/question randomization built into this presentation on purpose (for
concept reinforcement and to get you into exam thinking mode).
Hematopoiesis-An Overview
Q1
A 7 month old infant has the sudden onset of severe abdominal pain and cramping accompanied by chest pain,
nonproductive cough, and fever. On PE, his temperature is 39 degrees, pulse is 130/min, respirations are 25/min, and
blood pressure is 90/60 mmHg. He has diffuse abdominal tenderness but no masses or organomegaly. Lab studies show
a Hematocrit of 20%. The peripheral blood smear is shown in the figure below. Assuming the infant in question had this
problem at birth, the most likely explanation for the delay in his current symptoms is?
a. The protective effect of IgG antibodies transmitted from the mom to the infant in utero.
b. The protective effect of a tetrameric hemoglobin molecule that is typically increased in Beta thalassemia minor.
c. The protective effect of a tetrameric hemoglobin molecule that has a high affinity for oxygen compared to
Hemoglobin A in utero.
d. High titers of specific immunoglobulins originating from stem cells in the peritubular capillaries of the kidney.
e. High titers of a growth factor that encourages erythropoiesis.
Q1 Key
-This child most likely has Sickle Cell Disease so the best answer is C.
-Most infants with Sickle Cell Disease begin to present with symptoms at the age of 6
months when titers of Hemoglobin F begin to reduce in red blood cells.
-Remember that Hemoglobin F contains 2 alpha and 2 gamma subunits.
-Other important Hemoglobins include Hemoglobin A (normal Hb) which has 2 alpha
and 2 beta subunits and Hemoglobin A2 which has 2 alpha and 2 delta subunits.
Q2
A 67 yo man with a history of chronic gastritis presents with increasing fatigue and a
tingling sensation in his toes and fingers that have worsened over the past few months.
Blood work is performed with results revealing a hemoglobin of 10 g/dL and a Mean
Corpuscular Volume of 117fl. Which of the following patient profiles presents with the
most similarity to the pathophysiology underlying the symptoms present in our 67 yo
patient?
a.
b.
c.
d.
e.
Q2 Key
-The best answer to this question is D, a prior history of small bowel resection
secondary to Crohns disease.
-Remember that the ileum is the primary site of absorption of Vitamin B12 into the
bloodstream. This absorption is mediated by the binding of B12 complexed with IF to
Transcobalamin 2 receptors.
-Anything that causes malabsorptive disease can also cause a B12 deficiency.
-Folate deficiency also presents with megaloblastic anemia (are there neurologic
symptoms??). Folate is absorbed in the duodenum and proximal jejunum (for the
future-folate is absorbed only in the jejunum).
Megaloblastic Anemia
-Is a subset of the group of anemias known as the macrocytic anemias.
-These anemias are for the most part secondary to B12 or Folate Deficiency.
-If you have any remote mention of Neurological Symptoms on your exam, choose a B12 deficiency as the most
likely cause.
-The hallmark histologic finding in megaloblastic anemia is the presence of hypersegmented neutrophils (be
able to recognize this for your test!). These arise from cell growth without division due to a lack of DNA
synthesis. Ovalocytes may also be seen on a blood smear (RBCs that look like potatoes).
-Folate and B12 are both required for nucleotide synthesis. The absence of DNA prevents nuclear maturation in
the presence of cytoplasmic expansion (prior to mitosis). As a result, cells get bigger. Note that the cells still
have the ability to expand because they can still make mRNA and proteins which are required for cellular
expansion (membranes, etc).
Q3
A woman presents to the Med19 free clinic with signs and symptoms of leg pain and
swelling that arose over the last 3 days. Her D-dimer levels are elevated which raises
your suspicion of a DVT. In the process of conducting other blood studies, you notice
an elevated beta HCG level and Ultrasound reveals a 4 week old fetus. What is the
mechanism of action of the drug that best decreases the risk of adverse events as a
consequence of the DVT?
a.
b.
c.
d.
e.
Q3 Key
-This question is trying to test your ability to recognize 1 key concept.
-The best answer is A which is Heparin.
-This woman has a DVT which has a high risk of breaking off and getting to the
pulmonary artery (giving rise to a Pulmonary Embolus).
-Heparin does not lyse clots, but it prevents new ones from forming.
-Our patient is pregnant, so she should not get Warfarin which is a teratogen. Heparin
is the DOC in the treatment of hypercoagulable states in pregnancy. Heparin is protein
bound which severely decreases its bioavailability and hence its transmission to the
fetus through the placenta.
Q4
A 35 yo smoker is admitted to the hospital with signs and symptoms of acute chest
pain with radiation to the jaw. Serial ECGs indicate the presence of an ongoing
myocardial infarction. Thrombolytic therapy is rapidly initiated with prompt
resolution of the patients symptoms. 4 hours later, the patient begins to have seizures
with subsequent bleeding from his ears. Reversal of these acute symptoms can best be
established by the administration of a drug that;
a.
b.
c.
d.
e.
Activates plasminogen.
Degrades fibrin.
Activates fibrinogen.
Inhibits plasminogen conversion to plasmin.
Inhibits fibrinogen conversion to fibrin.
Q4 Key
-The best answer to this question is D.
-The patient in question most likely has an occlusion of one of his coronary arteries
leading to an acute MI.
-A clot busting drug like Streptokinase was used to open up the blockade and
reperfuse the heart. These drugs literally bust every recently formed clot in the body
and hence present a really high bleeding risk (are heavily contraindicated in lots of
patients).
-Reversing the bleeding associated with these drugs depends on preventing the
conversion of plasminogen to plasmin by the administration of Aminocaproic Acid.
This is the rescue agent in bleeding secondary to thrombolytic therapy.
Q5
A 44yo man who recently underwent a Coronary Angioplasty receives a 6 month
prescription for an injectable monoclonal antibody that interferes with platelet
aggregation. The mechanism of action of this drug produces physiological effects that
are most similar to a patient with?
a.
b.
c.
d.
e.
Q5 Key
-The best answer is E, Glanzmann Thrombasthenia.
-The drug in question is Abciximab which inhibits the platelet receptor, Gp 2B/3A.
-The inhibition of this receptor shuts down platelet aggregation (it is actually HY to
know the particular step in the platelet plug formation process that is inhibited by a
drug, they love testing those!).
-An individual with Glanzmann Thrombasthenia (a genetic deficiency in the Gp 2B/3A
receptor) essentially has a naturally occurring platelet aggregation problem.
Q6
A 19 yo. medical student is enrolled in a clinical trial for a new thrombolytic agent.
While signing a disclosure form, he mentions having a genetic disorder that leads to a
decreased inactivation of Factor 10 and Thrombin. To confirm this disclosure,
experimental assays are conducted with samples drawn from his serum. The most
plausible result of this experiment is;
a.
b.
c.
d.
e.
f.
g.
Q6 Key
-The best answer is F.
-An inability to inactivate Factor 10 and Thrombin (Factor 2) is the primary
pathophysiology behind Antithrombin 3 deficiency.
-Heparin works by increasing the activity of Antithrombin 3. Therefore, these
individuals would have no response to AT3 or would need a larger than normal dose of
Heparin to achieve the same therapeutic effect.
-For annoying questions like these, come up with your answer first before sifting
through the mess in the answer choices provided so you dont get confused and get an
unnecessary headache.
Clot Haters
-Antithrombin 3 inhibits Factors 2, 7, 9, 10, 11, and 12 (mostly know 2 and 10). It is activated by
Heparin (which is also naturally released by basophils/other blood and tissue elements).
-Prostaglandin I2/PGI2 (consider this to be a platelet gathering inhibitor) is made by
endothelial cells and inhibits platelet aggregation. PGI2 is also a powerful vasodilator. By
vasodilating, PGI2 increases blood flow to an area and washes away platelet plugs.
-Protein C and S are Vitamin K dependent proteins that inactivate Factors 5 and 8 which are
accelerating factors of the coagulation cascade (b/c they serve as cofactors for other factors in
the pathway). A thrombin-thrombomodulin complex on endothelial cells activates Protein C.
Protein S acts as a cofactor for Protein C.
-Tissue Plasminogen Activator (tPA) is made by endothelial cells. tPA converts plasminogen to
plasmin. Plasmin degrades fibrin and other coagulation factors.
Clot Lovers
-TXA2 is made by platelets and plays 2 roles. The first is the promotion of platelet aggregation. The 2nd is the
promotion of vasoconstriction. Note that vasoconstriction is pro-thrombotic because it prevents formed
platelet plugs from being washed away.
-VWF is made by platelets (stored in alpha granules) and endothelial cells (stored in Weibel Palade bodies).
VWF has 2 main functions-the first being an involvement in the adhesion step of primary hemostasis (forming
the platelet plug) and the 2nd being a carrier of Factor 8 (prevents degradation)..
-The release of VWF from Weibel Palade bodies is promoted by a drug known as Desmopressin which is an
analogue of ADH. Hence Desmopressin is the DOC in the treatment of Hemophilia A which is an X linked
recessive disease.
-Why does this make any sense? Teleologically, ADH is antidiuretic and hence prevents water losses from the
body. 1 secondary role of ADH (GTS Endo) is to constrict blood vessels. So it should make sense that it would
promote the release of something that is pro-thrombotic so you dont lose fluid from the body.
-What should be true of the PT, PTT, and Bleeding Time in Von Willebrand Disease?
Q7A
A 27 yo. pregnant woman from West Africa presents to the ER with an acute
complaint of blood in her stool. PE reveals petechiae on her skin and buccal mucosa,
HR of 35 bpm, BP of 90/50. The patient suddenly begins to cough up blood. A CBC
reveals anemia and thrombocytopenia. The patient takes a Folate supplement daily.
Choose the set of values that best agree with this patients presentation.
Q7B
A 27 yo. pregnant woman from West Africa presents to the ER with an acute
complaint of blood in her stool. PE reveals petechiae on her skin and buccal mucosa,
HR of 35 bpm, BP of 90/50. The patient suddenly begins to cough up blood. A CBC
reveals anemia and thrombocytopenia, PT and PTT are elevated. The patient takes a
Folate supplement daily. Which of the following would be expected on a blood smear
obtained from this patient?
a.
b.
c.
d.
e.
Spherocytosis
Howell Jolly Bodies
Schistocytosis
Heinz Bodies
Bite cells
Q7A/B Key
-The best answer is E for Part A and C for Part B .
-A description detailing a pregnant woman with acute complaints of hemoptysis and
blood studies revealing thrombocytopenia and anemia is classic for DIC (Disseminated
Intravascular Coagulation) which is common in this patient population.
-The best test in this scenario is a D-Dimer test which is indicative of some sort of clot
breakdown. For the future, the D-dimer test is highly sensitive but not specific (this
factoid is commonly framed as a heme question in the context of biostatistics).
-The spill about West Africa is a distractor to get you to think about some sort of
G6PD deficiency but this is usually framed in the context of exposure to some sort of
drug or consuming a meal (read your Qs carefully).
Thrombolytics
-Our innate clot busting molecule is plasmin, which is made from plasminogen by
TPA.
-Recombinant TPA can be given in the setting of an MI or Thromboembolic stroke.
-These drugs tend to end in plase-Alteplase, Tenecteplase, etc. The only key
exception is Streptokinase which is not used anymore as a result of potential immune
mediated reactions (why??).
-Since these drugs bust clots, there is a very huge associated bleeding risk.
-The rescue agent in toxicities associated with these clots include Aminocaproic Acid
and Tranexamic Acid. These drugs are competitive inhibitors of plasmin, hence
preventing the conversion of fibrin to fibrin degradation products.
Anemia
-There are 3 different kinds of Anemias.
-The first group are Microcytic Anemias (MCV < 80). There are 4 majors here-Fe Deficiency
Anemia, Anemia of Chronic Disease, Thalassemias, and Sideroblastic Anemias.
-The second group are the Macrocytic Anemias (MCV > 100). The major group here are anemias
secondary to B12/Folate Deficiency.
-The 3rd group are the Normocytic Anemias (MCV b/w 80-100). These anemias are typically
differentiated based on reticulocyte (an immature RBC) counts. If reticulocyte counts are low,
consider Renal Disease or Aplastic Anemia (indicative of underproduction). If reticulocyte counts
are high, consider hemolytic anemias (i.e. Sickle Cell Disease, G6PD deficiency, Hereditary
Spherocytosis, Autoimmune Hemolytic Anemia, Microangiopathic Hemolytic Anemias).
-It is very important to have anemias classified in your mind as a means of coming to a
differential on the exam and making the right diagnosis.
Q8
The photomicrograph shown below is most consistent with a patient having a prior history of?
a.
b.
c.
d.
Q8 Key
-The best answer is A.
-The arrow points to a Howell Jolly body.
-Howell Jolly bodies are nuclear remnants that are typically removed by macrophages
in the spleen. The presence of a Howell Jolly body on microscopy is indicative of
asplenia or an auto infarcted spleen which is common in SCD patients.
-SCD patients typically present with pain in the digits (dactylitis) from recurrent vasoocclusive episodes and infarction of the wrist/hand bones.
Q9
A concerned parent brings her 3 month old child to the ER. She mentions that her son
s urine has been red for the last few days. He has never had these symptoms before.
Blood smear obtained from the child indicates RBCs lacking central pallor. Blood
studies conducted in this patient would most likely reveal?
a.
b.
c.
d.
e.
An increased MCHC.
A decreased MCHC.
Increased haptoglobin.
Conjugated hyperbilirubinemia.
An abnormally low level of reticulocytes.
Q9 Key
-The best answer is A.
-RBCs without central pallor is indicative of spherocytes.
-Spherocytes have a decreased SA/V ratio and hence an increased Mean Corpuscular
Hemoglobin Concentration (MCHC).
-Know the common descriptors and morphologies of RBCs under different pathologic
conditions.
Q10
A healthy 17 yo. female suffered blunt abdominal trauma in a MVA. Her CBC on
admission showed a Hct of 33% which decreased to 25% over the next hour. In the
process of treatment and supportive care, 1L of bloody fluid was evacuated from the
patients abdomen with marked improvement of her symptoms. A CBC performed 3
days later is most likely to reveal which of the following RBC morphologies.
a.
b.
c.
d.
e.
f.
Basophilic Stippling
Hypochromic RBCs
Leukocytosis
Reticulocytosis
Schistocytosis
Spherocytosis
Q10 Key
-The best answer is D.
-The acute blood loss precipitates an anemic signal which in the presence of normal
Fe stores (as is this case for this healthy female) stimulates reticulocytosis from the
bone marrow.
-A good mental exercise will be to defend why the other answers are wrong.
Q11
A 4 yo. boy from Palermo has a poor appetite and is underweight for his age. PE
reveals hepatosplenomegaly. Blood studies reveal a Hb of 6 g/dL, MCV of 60 fL,
normal levels of serum Fe, a reticulocyte count of 12%, and RBCs with widened central
pallor. Skull radiographs reveal facial deformities and expansion of marrow spaces. The
most likely cause of this childs illness is;
a.
b.
c.
d.
e.
Q11 Key
-The best answer is A.
-Any mention of the Mediterranean on your exam is most likely going to be BetaThalassemia. With major symptoms like this, our patient most likely has Beta-Thal
major.
-Anemia associated with beta-thal major increases EPO synthesis from the kidneys
which leads to marrow expansion and extramedullary hematopoiesis (this explains the
hepatosplenomegaly and facial deformities).
-These patients tend to require frequent transfusions and may eventually develop
secondary hemochromatosis (from Fe overload).
Q12
A 35 yo. woman from Vietnam prematurely delivers a markedly hydropic stillborn
infant. Autopsy reveals massive hepatosplenomegaly, cardiomegaly, and fluid in
multiple body cavities. There is marked extramedullary hematopoiesis. Hb
electrophoresis of the deceased infants RBCs would most likely reveal a predominance
of;
a.
b.
c.
d.
e.
f.
HbA
HbA2
Hb Barts
HbF
HbH
HbY
Q12 Key
-The best answer is C.
-This child most likely has Alpha Thal major which is associated with a 4 alpha globin
gene deletion. A complete lack of Alpha chains prevents the formation of HbF, A, and
A2. These leads to the formation of Gamma tetramers (Hb Barts) which leads to a
severe anemia.
-The severe hypoxia in utero leads to eventual cardiac failure and hydrops fetalis
(mechanism explained in Microbiology slides).
-Do not forget the SE Asia connection with Alpha Thal major.
Q13
A 25 yo. healthy Nigerian passes dark brown urine 2 days after starting prophylactic
malaria treatment for hypnozoite forms of the offending organism. PE is unremarkable
with CBC showing a markedly decreased serum haptoglobin. The most likely
explanation for these findings is;
a.
b.
c.
d.
e.
f.
g.
Q13 Key
-The best answer is F.
-This patient (a person of W. African origin) was most likely taking Primaquine which
places oxidative stress on RBCs. An individual with G6PD deficiency is not able to
handle this and would have hemoglobin cells undergoing oxidative damage. These Hb
inclusions can damage the RBC membrane resulting in intravascular hemolysis with
decreased haptoglobin. RBCs with these inclusions could also be destroyed by splenic
macrophages which results in extravascular hemolysis and elevated indirect bilirubin.
-Do not forget the fact that the Hb inclusions in G6PD deficiency are known as Heinz
bodies and splenic macrophages could remove these inclusions, leading to the
formation of bite cells.
Fe Studies-Ferritin
-Is the storage form of Fe and is made in the liver/bone marrow macrophages.
-Is an acute phase reactant and hence is increased in inflammation. This is partly why
Fe stores are increased in Anemia of Chronic Disease.
-Serum Ferritin is low in Fe Deficiency Anemia (when you see a problem that involves
a low MCV, the very first thing you should look for is the Ferritin level).
-Serum Ferritin is increased in Anemia of Chronic Disease and Hemochromatosis (or
any Fe overload state).
-Hemosiderin is the breakdown product of Ferritin (for your exam though, know
Hemosiderin as the super long term storage form of Fe).
Fe Studies-Serum Fe
-Is a measure of the amount of Fe bound to Transferrin.
-Serum Fe is decreased in IDA and ACD.
-Serum Fe is increased in Hemochromatosis (and other Fe
overload states).
Fe Studies-TIBC/Transferrin
-Transferrin is the protein that transports Fe in the blood (Fe is too dangerous to wander on its
own in serum).
-TIBC literally means TOTAL FE BINDING CAPACITY which is a measure of the space left
unoccupied on transferrin for Fe to bind to.
-An individual that is Fe deficient should open up more Transferrin Slots so he can get Fe to his
bone marrow. The level of Ferritin in the bone marrow has a feedback effect on the livers
production of Transferrin. High ferritin levels feedback inhibit the livers production of
Transferrin and vice-versa.
-Ferritin is low in IDA so TIBC should be high.
-ACD and Hemochromatosis are high Ferritin diseases, so TIBC is low.
Microcytic Anemias
-Are all secondary to decreased Hb Synthesis.
Why Microcytosis?
-MCHC is a very important consideration for RBCs.
-MCHC is essentially a mass/volume relationship. In this case, the mass is Hb and the
volume is the MCV.
-With a decrease in Hb production, RBC homeostasis demands decreasing the
denominator in the equation (MCV) to achieve MCHC constancy. This is
accomplished by increasing RBC mitosis.
-At a certain point however, MCV becomes an important consideration. An MCV that
is too small makes O2 diffusion and carriage less efficient.
-When this MCV threshold is reached, RBCs resort to hypochromasia.
Thalassemias
-Thalassemias are diseases that involve a decreased production of the
globin part of hemoglobin. Theres Alpha and Beta Thalassemia.
-Alpha Thalassemia (Autosomal Recessive) involves a decreased
production of Alpha globin chains. There are a few HY things to note
here-alpha globin is present in ALL hemoglobin types (A, A2, and F)
and there are 4 genes (2 on each chromosome) that affect alpha globin
chain expression. Alpha Thal is common in the Asian/African
American population.
-Mild Alpha Thalassemias are not necessarily picked up on Hb
electrophoresis. Why?
Beta Thalassemia
-Is a defect in beta globin gene production and could be caused by a myriad of mutations (very rarely gene
deletions, so this is NOT the right choice on an exam). Beta thal is common in African Americans, Greeks, and
Italians.
-There are 2 genes involved in Beta globin gene production.
-A 1 gene mutation is known as beta thal trait. Since beta globin goes down, the only Hb that will be decreased
will be HbA. As a result of this decrease, there will be a compensatory increase in other kinds of Hemoglobin
like HbA2 which DOES NOT require beta chains. An increase in HbA2 is diagnostic of Beta Thal trait.
-A 2 gene mutation in beta globin genes is compatible with life but these individuals are heavily dependent on
transfusions. Theres a marked increase in HbA2.
-Regular transfusions predisposes an individual to Fe overload (secondary hemochromatosis) which could be
fatal. The DOC in this situation is an Fe chelator like Deferoxamine. The definitive cure for Beta Thal is a Bone
Marrow Transplant (to reconstitute the blood lineage).
Hb electrophoresis is useful in the diagnosis of all forms of Beta Thalassemia. Why?
Hemoglobin Variants
Q14
A 16 yo. native of Kentucky comes to his PCP for an annual check up. He alludes to having tingling sensations
in his palms and occasional episodes of dizziness. A CBC/Blood smear reveal macrocytosis and hypersegmented
neutrophils. A diagnosis of Vit B12 deficiency is made. Prior to maintenance treatment, his PCP administers a
large, bolus IV dose of Vit B12. She subsequently administers an oral dose and tells the patient to collect and
return a urine sample the next day. Lab analysis indicates abnormally low levels of Vitamin B12 in the urine.
Concerned, the PCP administers the same oral dose of Vitamin B12 conjugated with another oral agent and
asks the patient to collect another urine sample. Measurements of B12 the next day reveal levels consistent with
experimental controls. Further work up of this patients condition would most likely reveal;
a.
b.
c.
d.
e.
Q14 Key
-The best answer is D.
-This patient most likely has Pernicious Anemia.
-The IV dose of Vit B12 administered earlier saturates all body stores of B12.
Administration of an oral dose should be accompanied by high levels of B12 in the
urine since it is excreted by the kidneys. Low levels of B12 in this scenario could mean
one of 2 major things-the intestinal brush border has problems OR the patient has a
deficiency of intrinsic factor.
-The correction of our patients problem with the administration of IF rules out
intestinal malabsorption as the cause of his B12 deficiency.
-Youll learn more about this famous test in your GI block (The Schilling Test).
Intravascular/Extravascular Hemolysis
Q15-Matching Game
Match these lab measurements to the most likely pathology.
Pathologies
A-Heparin/Warfarin administration.
B-Aspirin/NSAID administration.
C-Disseminated Intravascular Coagulation
D-Hemophilia A
E-Von Willebrand Disease
F-Thrombocytopenia
Lab Measures
Q15 Key
Heparin/Warfarin administration is E.
Aspirin/NSAID administration is B.
DIC is D.
Hemophilia A is C.
VWD is E.
Thrombocytopenia is A.
Triggers
Homocysteinemia/Methylmalonic acidemia
Hemolytic Uremic Syndrome
Anemia in the setting of an elevated creatinine
Hematuria after consuming Fava Beans
Elevated bleeding time only, platelet adhesion defect
Elevated bleeding time + increased PTT, platelet adhesion defect
Single factor deficiency with elevated PT only
Bronze skin, diabetes, cirrhosis, elevated Ferritin
Receptor defect, increased bleeding time, normal Ristocetin assay
Microcytic Anemia with Basophilic Stippling
Fever,Anemia,Thrombocytopenia,Renal Failure,Neuro deficits
Increases synthesis of HbF
Characteristic Blood Smear finding in Megaloblastic Anemia
Potent platelet aggregator and vasoconstrictor
Hematuria in the setting of increased RBC osmotic fragility
Rescue agent in Heparin toxicity
Rescue agent in Warfarin Toxicity
Best test for VWD/Bernard Soulier Syndrome
Best Screening Test for Fe deficiency Anemia/Anemia of Chronic Disease
Trigger Key
Homocysteinemia/Methylmalonic acidemia-B12 deficiency
Hemolytic Uremic Syndrome-E. Coli O157:H7
Anemia in the setting of an elevated creatinine-Kidney Failure
Hematuria after consuming Fava Beans-G6PD deficiency
Elevated bleeding time only, platelet adhesion defect-Bernard Soulier Disease
Elevated bleeding time + increased PTT, platelet adhesion defect-VWD
Single factor deficiency with elevated PT only-Factor 7 deficiency
Bronze skin, diabetes, cirrhosis, elevated Ferritin-Hemochromatosis
Receptor defect, increased bleeding time, normal Ristocetin assay-Glanzmann Dz.
Microcytic Anemia with Basophilic Stippling-Lead Poisoning.
Fever,Anemia,Thrombocytopenia,Renal Failure,Neuro deficits-TTP
Increases synthesis of HbF-Hydroxyurea
Characteristic Blood Smear finding in Megaloblastic Anemia-Hypersegmented PMNs.
Potent platelet aggregator and vasoconstrictor-TXA2
Hematuria in the setting of increased RBC osmotic fragility-Hereditary Spherocytosis
Rescue agent in Heparin toxicity-Protamine Sulfate
Rescue agent in Warfarin Toxicity-Vitamin K (long term), Fresh Frozen Plasma (short term)
Best test for VWD/Bernard Soulier Syndrome-Ristocetin Cofactor Assay.
Best Screening Test for Fe deficiency Anemia/Anemia of Chronic Disease-Ferritin levels
HY Immunology Review
Some MS2
General Advice
-The material in GTS is very important and is very heavily tested on exams youll meet
in the future (Step 1 to be precise).
-Your principal goal in GTS is to learn the material well. Down the line, youll realize
that nothing can replace a solid foundation.
-Immunology is best understood as a story. If you see how things all fit together, things
get a lot more intuitive. And immunology cuts across lots of fields in medicine.
-GTS exams focus heavily on clinical vignettes so understanding will take you a long
way in seeing the context behind the question so you can pick the right answer.
C3 Spontaneous Cleavage
Lymphoid Cells
-Cannot be told apart on the basis of light microscopy (this is
simple, but HY!)
-Are told apart by virtue of CD markers.
-All T cells have CD3 with the more specific CD4 being for
helper T cells (the cell mediated bosses) and the more specific
CD8 being for the cytotoxic/cytolytic T cells.
Compare/Contrast-BCR vs TCR
The Immunoglobulin
-Has a variable region that determines the idiotype (antigen binding capacity).
-Has a constant region that determines isotype (generates job description). For
example, having an Alpha Isotype confers the ability to provide mucosal immunity.
-Is divalent (can bind 2 of the exact same antigen-there are exceptions like IgM!)
-Has a hinge region that confers flexibility and disulfide bonds b/w chains.
-The constant region is the C terminus of the protein and has a binding region for
complement.
-The hypervariable region (or FAB) makes up the N terminus of the protein.
A Little Conundrum
-There are literally millions of different bugs/antigens that run around in the
environment.
-These are all recognized by very specific BCRs and TCRs.
-If we had a gene for each of these, we would not have enough genes to go around for
all physiologic functions.
-In fact, we would need a lot more genes than we have now.
-We deal with this problem by doing some genetic tricks that involve recombinations...
Recombination Rules
-We deal with our little conundrum by using gene segment recombinations.
-These recombinations are undertaken by Recombinase genes encoded by RAG1/2.
-Heavy chain recombination occurs first (DJ then VDJ).
-Light chain recombination occurs next (VJ).
-This process occurs in T and B cells.
-The process in heavy chains (BCR) is analogous to the beta chain in TCRs.
-The process in light chains (BCR) is analogous to the alpha chains in TCRs.
-There are 2 recombination chances for heavy chains (mom and dad chromosomes).
-There are 4 recombination chances for light chains (Kappa/Lambda, Mom/Dad each).
Lymphoid Organs
-Could be primary (cells are born). These include the bone marrow/thymus.
-Could be secondary (matchmaking center for exposure to antigen). These include the
spleen for blood-borne antigens, lymph nodes for lymph/tissue borne antigens, and the
Mucosa Associated Lymphoid Tissue (MALT) for Gut tube associated antigens.
-All cells are born in the bone marrow (including T cells).
-T cells mature (and undergo selection) in the thymus.
-B cells are born and mature/undergo selection only in bone marrow.
B cell development
-Pro B cells are mainly at work in VDJ/heavy chain recombination.
-The production of light chains is the marker for a transition to Pre-B cells.
-The expression of IgM on the surface of a B cell marks the transition to an
Immature B cell. If this IgM binds to self antigens, it undergoes apoptosis here.
-With no binding to self antigen, a survival signal allows further development into a
mature B cell.
-This all occurs in the bone marrow and is antigen independent (exogenous antigen).
-Anything after this is antigen dependent (again, exogenous antigen).
T Cell Development
T Cell Development
-Occurs primarily in the thymus.
-Involves Positive Selection (testing the ability to bind MHC) and negative selection
(testing for the ability to bind MHC too well). This occurs in the Thymic Cortex.
-Cells that bind MHC 1 go on to become CD8+ Cytotoxic T cells (CD # * MHC #
always equals 8).
-Cells that bind MHC 2 go on to become CD4+ Helper T cells.
-One main function of the cells of the thymus is to expose the T cells to self antigens
for education prior to entry into the periphery.
MHC1
-Is expressed in all nucleated cells of the body (why?).
-Presents endogenous antigen that is unique to the cell (this is a very HY Point!).
-Is a derivative of the HLA-A,B,C gene pool.
-Is codominantly expressed (mom and dad).
-Is made of an Alpha chain and Beta-2 Microglobulin.
-Is very limited in the kind of antigen it can present (why?).
MHC1
MHC2
-Is expressed only by APCs (what are they?)
-Presents exogenous antigen to CD4+ Helper T cells.
-Is a derivative of the HLA-DP,DQ,DR gene pool.
-Is codominantly expressed (mom and dad).
-Is made of an Alpha and Beta chain (please! do not confuse with the Alpha/Beta chain
that also constitutes the TCR).
-Has more leeway in the kind of antigen it can present (why?)
MHC2
Q1
A 19 yo. sexually active male was admitted to the hospital 2 weeks ago for an acute
onset presentation of fever, chills, and other flu like symptoms. Physical exam reveals
an enlarged mass in the left posterior abdominal wall that is tender to palpation in
addition to cervical/postauricular lymphadenopathy. A biopsy was obtained for
analysis (shown below). Flow cytometry of tissues derived from the region indicated
by the white arrow would show an increased expression of?
a.
b.
c.
d.
e.
CD15
CD56
CD19
CD3
CD2
Q1 Key
-The answer is CD3.
-The history and age range are very consistent with a presentation of Infectious Mononucleosis.
-Common signs and symptoms include massive splenomegaly and lymphadenopathy (the immune response to
infection by the Epstein Barr Virus-EBV which is the most common cause).
-The term mass in the left posterior abdominal wall should point you towards the spleen.
-The red arrow points to a splenic artery so the area right around it must be the PALS.
-This is the T cell region of the Spleen.
-CD3 is a marker for all T cells.
-When studying in GTS and for exams in general, try to think of case scenarios like this that integrate multiple
disciplines. It is one of the better ways to learn things.
Opsonization
-Is a hugely important mechanism for enhancing the efficiency of phagocytosis. They
are somewhat akin to ubiquitin degradative signals that exist intracellularly.
-Is mediated by C3b and IgG (this is HY!!!!!)
-There are receptors for these 2 mediators on the surface of PMNs and Macrophages.
-This mechanism is analogous to, but not the same as Antibody Dependent Cellular
Cytotoxicity (ADCC).
-Clinical Correlate-S. Aureus has a protein (Protein A) that binds to the constant
region of IgG and short circuits this opsonization process.
Opsonization
Q2
A 15 yo. high school student is rushed to the hospital after consuming a Peanut Butter
and Jelly sandwich. There is diffuse swelling of his tongue with impending closure of
his airway. A bolus dose of epinephrine is administered to reverse his presenting
symptoms. The antibody that mediated his first reaction to this allergen is best
described as;
a)
b)
c)
d)
e)
Q2 Key
-Regardless of presentation, the first antibody created in response to the immune
systems first encounter with an antigen is IgM.
-Please do not make the knee jerk mistake of picking the answer that corresponds to
IgE on your exam (many do). The overwhelming presentation given in the question is
that of an anaphylactic reaction which on subsequent exposure is IgE mediated.
-The best answer is D which corresponds to IgM (is secreted as a pentamer with 2
antigen binding sites each and hence has an avidity of 10).
IgM
IgM
-Is the first antibody created by the adaptive immune system in response to an
invasion.
-Is secreted as a pentamer and hence has an avidity of 10.
-Does not cross the placenta (is too big).
-Is the best at activating the Classic complement cascade.
-Cannot participate in opsonization and hence cannot take part in ADCC (Antibody
Dependent Cellular Cytotoxicity).
Class Switching
you blank out on the exam, IgG will quite likely be the answer.
IgG
IgA
-Is the primary antibody involved in mucosal protection.
-Is the primary antibody secreted into the Colostrum (breast milk). Dont confuse it
with the only antibody that crosses the placenta (which is?)
-Is secreted from MALT in response to antigen presentation by M cells.
-Is secreted as a dimer with something called the secretory component which protects
it from the brutal environment of the mucosa (against proteolysis/to be secreted).
-Class switching is triggered by IL-5 and TGF-Beta.
-Does IgA have the highest avidity of all Immunoglobulins?
IgA
IgA Secretion
Q3
2 months into your rotation, a lady brings her 2 week old child to the office for his
recommended vaccinations. The mom, who has been on HAART for the past 10 years
is worried that her child may have contracted the offending organism transplacentally
or during delivery. Serum studies are conducted to allay the patients fears. The
presence of which of the following is most consistent with ruling in vertical
transmission?
a.
b.
c.
d.
e.
Q3 Key
-The best answer is C.
-The presence of IgG is not sufficient to rule in vertical transmission because IgG to
the p24 antigen may have been transmitted across the placenta to the infant.
-The presence of IgM while not conclusive, should warrant further consideration.
Remember that IgM is the first antibody produced to any infection and given the
history of birth (2 weeks), it is highly unlikely that the adaptive immune response has
kicked in to enforce class switching to any other immunoglobulin.
Types of Immunity
Q4
A 3 year old infant presents with severe GI distress and sinusitis. His mother reports
that he has had these symptoms on a recurrent basis about 6 months after he was born.
Serum protein electrophoresis conducted on a sample obtained from the infant
showed a predominance of a structure with heavy chains and light chains joined
together in a pentameric arrangement. The infants condition is most likely due to
which of the following pathologic processes?
a.
b.
c.
d.
e.
Q4 Key
-The best answer to this question is B.
-Serum electrophoresis indicating high levels of a pentameric immunoglobulin should guide you
towards super high levels of IgM.
-The cluster of mucosal symptoms should guide you towards a deficiency of IgA.
-A buildup of IgM (which does not require class switching) and a deficiency of another (IgA or really
any other Immunoglobulin) should hopefully clue you in on defective class switching.
-A defect in CD40L mediated class switching (remember Signal 2?) is one of the common causes of a
disease known as Hyper IgM syndrome.
-You most likely do not need to know the disease name per se, but you should understand the process
behind the disease. Be sure to read your questions carefully (CD4+ vs CD8+).
Q5
A puzzled medical team decides to crowdsource the Med19 class (currently taking
Immunology) for help with figuring out a complex case. The patient, who is currently
9 months old and has lived in the hospital all his life has had to receive treatment for a
large variety of viral infections. A possible pathophysiological process underlying this
childs disorder could be;
a.
b.
c.
d.
e.
Q5 Key
-The best answer is D.
-T cells are the bodys main defense against intracellular infections (viral).
-CD8+ cells require presentation of antigen on MHC1.
-This presented antigen comes from the transport of proteasome degraded antigen to
the Endoplasmic Reticulum with the aid of TAP proteins.
-A TAP deficiency can predispose an individual to recurrent viral infections.
-Again, this question tries to draw on your ability to understand processes as against
being simply able to regurgitate information (which you should still be able to do
though!).
Q6
An 18 yo. college student with a history of recurrent bacterial infections is brought in
by one of your Immunology professors for a clinical correlation. He receives specific
instructions not to disclose his diagnosis until the end of the session. This patient has a
history of recurrent infections and has so far required a constant intake of antibiotics.
His infections typically do not involve the formation of pus. Which of the following is
most likely deficient in this patient?
a.
b.
c.
d.
e.
IL-1
IL-3
IL-7
IL-8
IL-12
Q6 Key
-The best answer is D.
-An inability to form pus is consistent with a failed migratory acute inflammatory
response which could potentially be secondary to defects in Neutrophil chemotaxis to
a site of injury. This will ultimately lead to recurrent bacterial infections.
-IL-8 is the only chemotactic factor listed here (what are the others?)
-Even if you dont have a clue with regards to solving this problem, eliminate what is
obviously wrong. IL-1 mediates fever, IL-3 stimulates bone marrow hematopoiesis, IL-7
mediates lymphoid lineage differentiation, and IL-12 mediates TH0-TH1 cell
differentiation.
Type 2 HSRs
Type 3 HSRs
-Involves the formation of soluble antigen-antibody complexes.
-These complexes deposit in tissues like the kidneys.
-The antibody part of the soluble complex then triggers the complement cascade and
ultimate cellular destruction.
-A very HY example of a Type 3 HSR is Post-Streptococcal Glomerulonephritis.
-Clinical Correlate-This is a very common cause of a cluster of symptoms known as the
Nephritic Syndrome in kids with the associated hypertension, hematuria, and
periorbital edema. Classically associated with subepithelial humps on EM.
Type 4 HSR
-If you see any of the following words on your
exam-delayed type hypersensitivity, TB skin test,
coin/metal allergy-stop thinking, look for the
answer that says Type 4 HSR and move on.
-Is mediated primarily by CD4+ TH1 cells and also
by macrophages to an extent.
Transplants-HY Terms
-An AUTOGRAFT involves the transplantation of self organs-for example in burn
injuries.
-An ISOGRAFT/SYNGENEIC graft is transplantation with the relationship b/w the
donor/recipient being identical twinship (generally no problems, but still some very
minor rejection).
-An ALLOGRAFT is a transplant from a member of the same specie, i.e. the
transplants we are all familiar with.
-A XENOGRAFT is a transplant from a member of another species-very common in
heart valve transplants from pigs, cows, etc.
-Review Transplant
Immunology some more.
-All the best Thursday!
HY METABOLISM REVIEW
Some MS2
General Principles
-Glucagon leads to Phosphorylation through
Protein Kinase A
-Insulin leads to Dephosphorylation through
Protein Phosphatases
Quick Review-The CAMP pathway
And Remember...
Glycogen Synthesis precedes Fatty Acid Synthesis
(short term vs. Long Term) especially in the Liver.
Glycolysis-Entry
Entry-Contd
Glycolysis-Regulation
Glycolysis Take-Aways
-Substrate Level Phosphorylation
-Hexokinase, PFK-1, and Pyruvate Kinase are heavily regulated
-PFK-1 is the Rate Limiting Step
-Consumes 2 ATPs, Makes 4 ATPs, 2 net ATPs
-Makes 2 NADH
-LDH is important in conditions of hypoxia for NAD Regeneration
Clinical Correlates
-Pyruvate Kinase Deficiency-Hemolytic Anemia
-Myocardial Infarction (Hypoxia)-Coagulative Necrosis
-2,3 BPG (infants/mountain-climbers)
-Increased KM of Glucokinase-Maturity Onset Diabetes of The Young (MODY)
-Methemoglobin Reductase and O2 carriage by Hemoglobin
Galactose Metabolism
FRUCTOSE METABOLISM
Fates of Pyruvate
Special Mention-Carboxylases
Carboxylases are ABC Enzymes
Require;
A-ATP
B-Biotin (Vitamin B7)
C-CO2
TCA Takeaways
-Per Acetyl CoA (double for glucose)-2 CO2/3 NADH/1 FADH2/1 GTP (Substrate
Level Phosphorylation)
-Its a cycle, not a pathway for De-Novo glucose synthesis (sole duty is AcCoA
oxidation)
-Steps proximal to Succinyl-CoA cannot participate in gluconeogenesis (hence
Leucine/Lysine are strictly Ketogenic Amino Acids). Steps starting from Succinyl-CoA
are gluconeogenic (hence odd chain Fatty acids can make glucose-only exception)
-Isocitrate Dehydrogenase is the Rate Limiting Step
-Alpha Ketoglutarate Dehydrogenase requires Tender Loving Care For Nancy
TCA Takeaways-Contd.
-With enough energy, Citrate builds up and takes the FA Synthesis route (explains the
lag between Glycogenesis and Lipogenesis)
Oxidative Phosphorylation
Glycogenesis
-Storage form of Glucose (Osmotic Considerations)
-Contains Alpha-1,4 and Alpha-1,6 linkages (Rapid Release Considerations)
-Glycogen Synthase is employed in states of Physiologic Plenty-should be active
when dephosphorylated (Insulin) and vice-versa
Glycogenesis/Glycogenolysis
Branching/Debranching Enzyme
GLUCONEOGENESIS
Regulation of Gluconeogenesis
Gluconeogenesis-Note
-Gluconeogenesis occurring in the liver is not intended to provide glucose for the
liver-its for other tissues (brain)
-The energy required for Gluconeogenesis by the Liver comes from Beta Oxidation
Alcoholic Metabolism
NADPH-contd.
NADPH-contd.
Clinical Correlates
-Chronic Granulomatous Disease (susceptibility to
infection with Catalase Positive Organisms)
-G6PDH deficiency is protective against Malaria
(Why?)
Pyrimidine Synthesis
Purine Synthesis/Regulation
Other FAs
Fatty Acids-Note
-Palmitic Acid is the commonly regarded endpoint of FA Synthesis.
-Linoleic Acid and Linolenic Acid are essential FAs and must be made from the diet (we cannot add double
bonds past position 9)
-Linoleic Acid is the key precursor of Arachidonic Acid (acted on by COX/LOX which are targets of many
drugs)
-There are 2 naming systems for Fatty Acids (#Cs : # Double bonds AND the Omega System)
-In general, unsaturated FAs are liquids at room temperature and are safer
-Omega 3 FAs are Cardioprotective
Fatty Acids-Contd
-FA Synthesis occurs in the Cytosol
-Insulin promotes FA Synthesis so it should be obvious that the regulation involves
some sort of dephosphorylation.
FA Synthesis
FA Synthesis/Regulation
-Acetyl CoA Carboxylase is an ABC Enzyme. It is upregulated by Citrate and
Dephosphorylation through Insulin and inhibited by its product, Palmitoyl CoA.
-Malonyl CoA inhibits Carnitine Acyltransferase 1 which prevents newly synthesized
FAs from re-entry into the mitochondria to prevent a futile cycle with concurrent
Beta Oxidation.
-FA Synthase is a multisubunit enzyme. It holds the growing FA chain with an
enzyme known as Acyl Carrier Protein (ACP) which requires Vitamin B5 (Pantothenic
Acid).
-The only Cs found in the Final Fatty Acid come from Acetyl CoA, not CO2!
Triglyceride Synthesis
Triglyceride Synthesis
-The only source of glycerol-3-phosphate in the Adipocyte is DHAP!
-The liver in addition to DHAP has Glycerol Kinase (recycling mechanism)
-VLDL is made in the liver and is transported in the blood aboard an APOB100
Lipoprotein
-Chylomicrons are made in the small intestine and are transported aboard APOB48.
Beta Oxidation
An Aside...
Based on what we know about Alcoholic Biochemistry, which
of the following will be detected in greatest concentration in the
serum of a chronic alcohol user?
a. Acetoacetate
b. Beta Hydroxy Butyrate
Quick Quiz..
The fasting state is accompanied by an increase in activity of which of the following
enzymes?
a.
b.
c.
d.
e.
Lipoprotein Metabolism-introduction
-Lipoproteins are fat carriers in the blood.
-Some are exogenously derived (diet)-Chylomicrons
-Some are endogenously derived (from liver)-VLDL
-Lipoprotein Metabolism is very important in the
pathogenesis/treatment of Artherosclerotic/Hyperlipidemic
disorders.
Lipoprotein Metabolism
HDL/LDL Metabolism
Lipoprotein Summary
Quick Quiz..
Which of the following enzymes constitute the Rate Limiting
Step of the Urea Cycle?
a.
b.
c.
d.
Final Words..
HY Micro Pharmacology
Some MS2
Introduction
-For Micro Pharmacology, you should be able to know the major drug classes, the
drugs that fall into each class, the mechanism of action of each drug class, unique side
effects, and general ideas about the organisms covered by the drug.
-For a few organisms (Pseudomonas, atypical causes of Pneumonia, amongst others),
you should definitely focus on knowing the Drugs of Choice in such scenarios.
-Micro Pharm is important. If you learn it well now, and get the concepts down, youll
find it very useful in coming GTS blocks and on future exams.
Antibiotics Introduction
-The Minimum Inhibitory Concentration is the lowest concentration of drug needed to inhibit bacterial growth.
Is a bacteriostatic drug term.
-The Minimum Bactericidal Concentration is the lowest concentration of drug needed to kill 99.9% of bacteria.
Is a bactericidal drug term.
-Bacteriostatic Drugs are good for immunocompetent people. It slows the rate of bacterial growth which gives
the immune system time to kill the bug.
-Bactericidal Drugs are good for immunocompromised people. It kills off the bug completely (since their
immune systems are weak).
-Combination Therapy is typically given with Antibiotics to decrease resistance AND to achieve synergism (1+1
= 3).
Aminoglycosides
-Disrupt formation of the initiation complex and overall cause mRNA misreads.
-Include Gentamicin, Neomycin, Amikacin, Tobramycin, and Streptomycin (at the
very least, know the bolded ones).
-These drugs are nephrotoxic and ototoxic (CN8 lesions). They should not be given
with loop diuretics.
-They exhibit Concentration Dependent killing (like the Fluoroquinolones) and for
the most part cover only aerobic gram negative rods (they are not effective against
anaerobes). They also exhibit a PAE against Gram +ves.
-They exhibit synergism with beta lactams which create a pathway for cellular entry.
Tetracyclines
-Prevent the binding of the incoming Aminoacyl tRNA to the A site of the 30S subunit.
-Include Doxycycline and the newer drug with much less resistance-Tigecycline
(covers MRSA).
-Are the DOC for the treatment of Lyme Disease/Chlamydia/Rocky Mountain Spotted
Fever.
-These drugs SHOULD NOT be taken with Antacids (or things containing) divalent
ions to avoid drug chelation. This explains the HY side effect of tooth discoloration
with the tetracyclines.
-The key mechanism of resistance is increased efflux of the drug from cells.
Chloramphenicol
-Chloramphenicol inhibits Peptidyl transferase.
-Chloramphenicol has the HY side effect of Gray Baby Syndrome which is due to the
physiologic deficiency of UDP Glucuronosyl Transferase in infants which hampers
their ability to conjugate the drug and eliminate it. Theres also the risk of Aplastic
Anemia.
-Chloramphenicol is great for treating meningitis because it crosses the BBB fairly
easily.
-The mechanism of resistance is acetylation by an acetyltransferase encoded for by
plasmids.
Clindamycin
-Clindamycin inhibits peptide bond formation by binding to and inhibiting the 50S
subunit. Its MOA is essentially identical to that of a Macrolide.
-Clindamycin is commonly used to treat Anaerobic infections (like Bacteroides,
Fusobacterium, etc). A common exam buzzword is the coverage of Anaerobes above
the belt (contrast with Metronidazole which is for anaerobes below the
belt/diaphragm).
-One HY Side effect of Clindamycin is Pseudomembranous Colitis as it is particularly
effective at killing off all your gut flora.
Macrolides
-Block the translocation step of protein synthesis.
-Bacteria have a 50S (which has a 23S subunit) and a 30S subunit which forms a 70S
subunit.
-Macrolides bind to the 23S subunit and prevent movement between the A, P, and E sites.
-HY Macrolides include Erythromycin and Azithromycin.
-Macrolides are the DOC for Atypical Organisms like Mycoplasma, Chlamydophila, and
Legionella Pneumoniae. A tougher exam Q could be to decipher the DOC in the treatment
of Pneumonia secondary to infection with an intracellular organism (which these are).
However, note that Tetracyclines are also great drugs for treating intracellular organism
infections like Chlamydia (the UTI) or Rocky Mountain Spotted Fever.
-Reach for these drugs if a pt. has Penicillin allergies.
TMP-SMX
Trimethoprim-Sulfamethoxazole (TMP-SMX)
-Inhibit Folate Synthesis. TMP inhibits Dihydrofolate Reductase while
Sulfamethoxazole acts as a PABA analog that competitively inhibits Dihydropteroate
Synthase.
-Are typically given as a combination. Are individually bacteriostatic, but in
combination, are bactericidal.
-Are used for Pneumocystis Jirovecii prophylaxis in HIV patients when the CD4 count
dips below 200 (this is super HY!).
-They are also useful for UTIs.
-They may also cause a megaloblastic anemia as folate is needed for purine/pyrimidine
synthesis.
Metronidazole
-Forms toxic intermediates (mostly free radicals) that destroys the bacterium. Is the
DOC for the treatment of C. Difficile colitis. Another option is to try oral Vancomycin
(normally Vancomycin is given IV). Why do we give oral Vancomycin if it has zero
oral bioavailability?
-If you a get a question about someone that went camping, drank from a stream
because they were too thirsty, got home and had foul smelling diarrhea, what is the
offending organism? Metronidazole is the DOC in the treatment of this disorder.
-Metronidazole covers the Anaerobes below the belt.
-Metronidazole also covers Entamoeba Histolytica.
Daptomycin
-Creates pores/channels in the cell membrane.
-By creating these pores, ions flow down their gradients which leads to cellular
depolarization (basically the membrane potential gets thrown out of whack).
-This drug is myotoxic so a potential test question could frame this in the context of
elevated Creatine Kinase.
-Daptomycin covers only Gram +ves.
-Pay attention to the phrases, covers only...These are HY.
TB Meds
-TB Prophylaxis is accomplished with the drug Isoniazid.
-The treatment combo for TB is RIPE (Rifampin, Isoniazid, Pyrazinamide, and Ethambutol).
-All these drugs are Hepatotoxic, except Ethambutol (causes visual problems).
-Rifampin inhibits DNA dependent RNA Polymerase (in other words, it inhibits RNA Synthesis).
Read your answer choices carefully on the exam regarding the MOA. They love to mix and match
the words with things like RNA Dependent DNA Polymerase.
-Remember that Rifampin also serves as prophylaxis for N. Meningitidis (for treatment, pick
Ceftriaxone though) and H. Influenzae Type B.
-Rifampin upregulates Cytochrome P450 and hence increases the metabolism of other drugs
(contrast with Rifabutin).
TB Meds contd.
-Rifampin can cause orange tears/sweat/urine which is generally harmless. If you see
this side effect on your exam, stop thinking and pick Rifampin (could also be framed
as a change in the color of contact lenses).
-Isoniazid works to decrease the synthesis of mycolic acid.
-It is activated by Catalase-Peroxidase (expressed by the KatG gene, this is super HY!).
-INH is neurotoxic (can be prevented by giving Vitamin B6). They love framing this in
the context of a person being treated for TB developing peripheral neuropathy and
then asking what could have been done to prevent this sequelae. INH is also
hepatotoxic.
-Theres a difference in INH metabolism based on your status as being a slow/fast
acetylator.
TB Meds contd.
-Clinical Correlate/Biochemistry tie in (NOT on your test). INH inhibits the enzyme
that converts Vitamin B6 to its active form. Vitamin B6 is required for the conversion
of Glutamate to GABA via Glutamate Decarboxylase. With decreased GABA (which is
an inhibitory neurotransmitter), seizures develop as a SE of INH (neurotoxicity).
-INH resistance is mediated primarily by KatG or InH A mutations.
-Pyrazinamide inhibits the synthesis of the unusual fatty acids in the mycobacterial cell
wall. It is highly effective in low pH environments. A HY SE is gout (hyperuricemia).
-Pyrazinamide requires activation by the TB bug itself (Pyrazinamidase which is
encoded by the pncA gene).
-Knowing these TB drug genes is HY for your test.
Antifungals-in 1 slide
HIV
HIV Pharmacology
Other Antivirals-Ganciclovir/Foscarnet
-Ganciclovir is the DOC in the treatment of CMV infections.
-Ganciclovir works exactly like Acyclovir. The only key difference is in the method of
activation which is via a CMV encoded kinase (this is why Acyclovir is not effective in
CMV).
-The primary resistance mechanism with Ganciclovir is a mutation in the viral
encoded UL97 Kinase.
-Foscarnet is somewhat analogous to Nevirapine. It is a pyrophosphate analog that
inhibits DNA Polymerase in a noncompetitive fashion and is the DOC in Acyclovir
resistant Herpes/VZV infections.
Anti-Influenza Antivirals
-Oseltamivir and Zanamivir inhibit Neuraminidase which is required for Influenza
exit from an infected cell.
-Amantadine inhibits viral uncoating but is no longer used due to massive resistance.
Amantadine increases the release of Dopamine from neurons and is now used to treat
Parkinsons Disease.
HY Microbiology Review
Some MS2
Q1
2 days after paying a visit to the dentist, Mr. X begins to experience mild facial pain. 10
days later, he presents to the ER with a moderately expanded right jaw. Physical
examination reveals an abscess with draining pus of a yellow consistency. Which of the
following best describes the organism responsible for this mans symptoms?
a.
b.
c.
d.
e.
Q1 Key
-The right answer to this question is C (Actinomyces Israelii).
-This is a gram positive filamentous rod associated with facial infections that drain as
Sulfur granules. A. Israelii is a gram positive obligate anaerobe. Anaerobes by
definition, lack catalase and superoxide dismutase.
-Key Buzzwords for this bug-Sulfur granules, draining abscess that looks like gold,
cervicofacial infection, cutting across tissue planes.
Q2
A Med19 student presents to the Charm City clinic with a fever of 103 degrees, facial
palsy, headache, and malaise. A circular, maculopapular rash was identified on his
shoulder. Which of the following routes best describes the method of infection
acquisition in this unfortunate Med19 student?
a.
b.
c.
d.
e.
Q2 Key
-The best answer to this question is B (Arthropod Vector-the Ixodes tick which carries the causative Borrelia
Burgdorferi organism).
-The infection in question is Lyme disease.
-The typical presentation is that of a maculopapular rash with central clearing with an associated
fever/migratory joint arthritis.
-Lyme disease is very HY and occurs in stages with Stage 1 having the presentation of the rash, Stage 2
involving cardiac and facial problems, and Stage 3 involving CNS problems. Treatment is with Doxycycline
(what is the MOA?)
-Key Buzzwords-Erythema Chronicum Migrans (maculopapular rash with central clearing), travel/hiking
history encompassing the Boston, Connecticut, New Hampshire area (Northeastern US), facial paralysis (Bells
Palsy), Ixodes tick, Borrelia Burgdorferi, migratory arthritis.
-Dont confuse the Erythema Migrans of Lyme Disease with the Erythema Marginatum of Group A Strep!
Q3
A 4 year old child of an Eastern European immigrant family is brought to the Med19 free clinic.
The child is afebrile, but weak and exhausted from a week of relentless coughing with inspiratory
whoops that puts him out of breath. A blood sample drawn for analysis indicates a WBC of 75,000
with a predominance of lymphocytes. The symptoms present in this child would most likely have
been prevented by which of the following interventions?
a.
b.
c.
d.
Q3 Key
-The best answer is A (the DTaP vaccine).
-The causative organism here is Bordetella Pertussis which is associated with
whooping cough.
-There are 3 stages of infection-a catarrhal stage with mild flu like symptoms, a
paroxysmal stage with the whooping cough, and then a convalescent phase with a
milder cough (leading to ultimate recovery). Transmission is via respiratory droplets.
-Key Buzzwords-History of Immigration, whooping cough, history of cough for many
months. Note that the cough is associated with inspiratory whoops. Do not confuse
with the barking cough of Croup which is caused by the Parainfluenza virus.
Q4
Supply the name of the organism that best meets the following descriptions.
-Gram positive cocci in pairs
-Gram positive cocci in clusters
-Gram negative cocci in pairs
N/B-The words in pairs are equivalent to the word diplococci.
Q4 Key
Supply the name of the organism that best meets the following descriptions.
-Gram positive cocci in pairs-Streptococcus Pneumoniae.
-Gram positive cocci in clusters-Staphylococcus Species.
-Gram negative cocci in pairs-Neisseria Species.
N/B-The words in pairs are equivalent to the word diplococci.
Q5
What is the bug that is best described by the following info cluster?
-Acute Endocarditis
-Most common cause of Osteomyelitis
-Toxic Shock Syndrome
-Scalded Skin Syndrome
-2 hr Gastroenteritis (after consuming potato salad/mayonnaise)
Q5 Key
What is the bug that is best described by the following information cluster?
-Acute Endocarditis
-Most common cause of Osteomyelitis
-Toxic Shock Syndrome
-Scalded Skin Syndrome
-2 hr Gastroenteritis (after consuming potato salad/mayonnaise)
-Staphylococcus Aureus (is catalase and coagulase positive).
Q6
What is the bug that is best described by the following info cluster?
-Blood culture contaminant
-Normal skin flora
-Prosthetic valve endocarditis
-UTIs in individuals with indwelling catheters
Q6 Key
What is the bug that is best described by the following info cluster?
-Blood culture contaminant
-Normal skin flora
-Prosthetic valve endocarditis
-UTIs in individuals with indwelling catheters
-Staphylococcus Epidermidis (catalase positive, coagulase negative, novobiocin
sensitive).
Q7
What is the bug that is best described by the following info cluster?
-UTI in a sexually active young woman
-2nd most common cause of UTIs
Added question-What is the most common organism implicated in the vast majority of
UTIs?
Q7 Key
What is the bug that is best described by the following info cluster?
-UTI in a sexually active young woman
-2nd most common cause of UTIs
Added question-What is the most common organism implicated in the vast majority of
UTIs? (Escherichia Coli)
-Staphylococcus Saprophyticus (catalase positive, coagulase negative, Novobiocin
resistant).
Q8
What is the bug that is best described by the following info cluster?
-Normal vaginal flora
-Causes Neonatal Meningitis/Sepsis/Pneumonia
-Beta Hemolytic
-Bacitracin Resistant
Q8 Key
What is the bug that is best described by the following info cluster?
-Normal vaginal flora
-Causes Neonatal Meningitis/Sepsis/Pneumonia
-Beta Hemolytic
-Bacitracin Resistant
-Streptococcus Agalactiae (or Group B Strep, Catalase negative)
Q9
What is the bug that is best described by the following info cluster?
-Most common cause of Meningitis, Otitis Media, Pneumonia, and Sinusitis
Q9 Key
What is the bug that is best described by the following info
cluster?
-Most common cause of Meningitis, Otitis Media, Pneumonia,
and Sinusitis
-Streptococcus Pneumoniae (Catalase Negative, Diplococcus,
Alpha Hemolytic, has a capsule, optochin sensitive)
Q10
What is the bug that is best described by the following info cluster?
-Pharyngitis, Impetigo, Erysipelas.
-Cellulitis, Necrotizing Fasciitis.
-Rheumatic Fever, Glomerulonephritis.
Q10 Key
What is the bug that is best described by the following info cluster?
-Pharyngitis, Impetigo, Erysipelas.
-Cellulitis, Necrotizing Fasciitis.
-Rheumatic Fever, Glomerulonephritis.
-Streptococcus Pyogenes (Group A Strep, Beta Hemolytic-A does not mean alpha!,
Bacitracin sensitive)
Q11
What is the bug that is best described by the following info cluster?
-Subacute Bacterial Endocarditis
-Recent Dental Procedure
Q11 Key
What is the bug that is best described by the following info cluster?
-Subacute Bacterial Endocarditis
-Recent Dental Procedure
-Streptococcus Viridans (Alpha hemolytic, optochin resistant, no capsule, Oral Flora).
Endocarditis
-Is an inflammation of the endothelium lining the valves of the heart.
-Endocarditis is very HY for your exam. The typical presentation is that of a new onset
murmur.
-Endocarditis can be classified as being acute or subacute (more to come shortly).
Q12
What is the bug that is best described by the following info cluster?
-Painless black eschar
-Hemorrhagic Mediastinitis
-Spore forming
-Wool sorter/Postal worker
Q12 Key
What is the bug that is best described by the following info cluster?
-Painless black eschar
-Hemorrhagic Mediastinitis
-Spore forming
-Wool sorter/Postal worker
-Bacillus Anthracis (capsule made of glutamate-not polysaccharide, has edema factor
as a toxin which is an Adenylate Cyclase, gram positive bacillus).
Q13
What is the bug that is best described by the following info cluster?
-Grayish pseudomembrane.
-Toxin encoded by beta prophage.
-Unimmunized child having a Bulls neck appearance on physical exam
Q13 Key
What is the bug that is best described by the following info cluster?
-Grayish pseudomembrane.
-Toxin encoded by beta prophage.
-Unimmunized child having a Bulls neck appearance on physical exam
-Corynebacterium Diphtheriae (encodes the Diphtheria toxin for which a vaccine is
available, causes Diphtheria, can cause CNS/Cardiac problems if left untreated, gram
positive bacillus)
Q14
What is the bug that is best described by the following info cluster?
-Spontaneous abortion
-Mom consumed unpasteurized milk/dairy products
-Mom consumed meats at a deli
-Tumbling motility, Intracellular organism
-Uses a projectile mechanism to avoid the immune system
Q14 Key
What is the bug that is best described by the following info cluster?
-Spontaneous abortion
-Mom consumed unpasteurized milk/dairy products
-Mom consumed meats at a deli
-Tumbling motility, Intracellular organism
-Uses a projectile mechanism to avoid the immune system
-Listeria Monocytogenes (gram positive bacillus). Treated with Ampicillin (HY!)
Q15
What is the bug that is best described by the following info cluster?
-Capsule
-Bilateral Adrenal Hemorrhage
-Nuchal rigidity
-Vaccine available
Q15 Key
What is the bug that is best described by the following info cluster?
-Capsule
-Bilateral Adrenal Hemorrhage (Waterhouse Friderichsen)
-Nuchal rigidity (Meningitis)
-Vaccine available
-Neisseria Meningitidis (gram -ve coccus, has a capsule, associated with skin purpura).
Q16
What is the bug that is best described by the following info cluster?
-Ophthalmia Neonatorum
-Arthritis in a young individual.
Q16 Key
What is the bug that is best described by the following info cluster?
-Ophthalmia Neonatorum
-Arthritis in a young individual
-Neisseria Gonorrhoeae (gram -ve coccus, no capsule, no vaccine, associated with
Urethritis, Cervicitis, Pelvic Inflammatory Disease, arthritis in a sexually active young
person-this is super HY!)
Q17
What is the bug that is best described by the following info cluster?
-Bloody diarrhea
-Symmetric ascending paralysis
Q17 Key
What is the bug that is best described by the following info cluster?
-Bloody diarrhea
-Symmetric ascending paralysis (Guillain Barre Syndrome).
-Campylobacter Jejuni (gram -ve rod, associated with beef consumption, major cause
of bloody diarrhea in the US, grows at 42 degrees).
Q18
What is the bug that is best described by the following info cluster?
-Bloody diarrhea special
-Hemolytic Uremic Syndrome
-Travelers Diarrhea/Montezumas Revenge/Watery Diarrhea
-Lactose Fermenter
Diarrhea HY points
-Diarrhea typically could be classified as being secretory, osmotic, or bloody.
-Secretory diarrhea involves the active secretion of substances into the GI tract in many cases secondary to the
activation of Adenylate Cyclase which leads to chloride and water secretion into the GI Tract. This is
characteristic of V. Cholerae and Enterotoxigenic E. Coli.
-Osmotic Diarrhea is associated with the presence of osmotically active substances within the gut that draws
water and electrolytes into the lumen. Osmotic diarrheas are in many cases secondary to metabolic problems
(like lactose intolerance).
-Consider C. Difficile as the cause of diarrhea (secretory) in an exam scenario involving diarrhea after a course
of antibiotics (notably Clindamycin). Destruction of gut flora provides ample room for C. Difficile overgrowth.
-It is extremely HY to know that in many cases, diarrhea is self limited and for the most part just requires fluid
and electrolyte replacement. They love testing this!
Q19
What is the bug that is best described by the following info cluster?
-Typhoid Fever
-Bloody diarrhea
-Osteomyelitis in a sickle cell patient
Q19 Key
What is the bug that is best described by the following info cluster?
-Typhoid Fever-Salmonella Typhi (Rose Spots on the Abdomen)
-Bloody diarrhea
-Osteomyelitis in a sickle cell patient
-Salmonella Species
Q20
What is the bug that is best described by the following info cluster?
-Fecal Oral Transmission
-Only about 10 organisms required
-Really nasty bloody diarrhea preceded by watery diarrhea
-Toxin mediated Gastroenteritis
Q20 Key
What is the bug that is best described by the following info cluster?
-Fecal Oral Transmission
-Only about 10 organisms required
-Really nasty bloody diarrhea preceded by watery diarrhea
-Toxin mediated Gastroenteritis
-Shigella
Q21
What is the bug that is best described by the following info cluster?
-MALT Lymphoma
-Peptic Ulcer Disease
-Urease positive
-Gastric Cancer
-Triple Therapy
Q21 Key
What is the bug that is best described by the following info cluster?
-MALT Lymphoma
-Peptic Ulcer Disease
-Urease positive
-Gastric Cancer
-Triple Therapy (Clarithromycin, Amoxicillin, and a Proton Pump Inhibitor)
-Helicobacter Pylori
Q22
Supply the organisms that are associated with the following.
-Whooping Cough
-Undulant fevers
-Gram -ve cause of Otitis Media
-Pneumonia from air-conditioning/water source
-Pseudoappendicitis like diarrhea.
Q22 Key
Supply the organisms that are associated with the following.
-Whooping Cough-Bordetella Pertussis
-Undulant fevers-Brucella
-Gram -ve cause of Otitis Media-Haemophilus Influenzae
-Pneumonia from air-conditioning/water source-Legionella Pneumophila
-Pseudoappendicitis like diarrhea-Yersinia Enterocolitica
Q23
What is the bug that is best described by the following info cluster?
-Burn patients/Wet environments
-Pneumonia in Diabetic patients
-Otitis Externa
-Osteomyelitis in diabetics
-Hot Tub Folliculitis
-Blue green pigment
-Ticarcillin/Piperacillin treatment
Pneumonia
-Pneumonia is extremely high yield for your exam.
-Is associated with alveolar inflammation.
-Can be grouped as being typical with the patient feeling really ill and having a lobar infiltrate on CXR OR being
atypical with the patient having fairly mild symptoms and an interstitial infiltrate on CXR (CXR looks worse than the
patient).
-Theres also aspiration pneumonias that have very strong associations with obtunded states like Alcoholism,
Nasogastric Tubes, etc. Obtunded states suppress the cough reflex which is important for microbe clearance.
-Ventilators are associated with Pneumonia because the patients respiration effectively bypasses the mucosal
protection of the Upper RT and grants direct entry to the lungs.
-The Drug of Choice in the treatment of Pneumonias secondary to Anaerobic Infection is Clindamycin (the so-called
Anaerobes above the belt).
-Your key Pneumonia takeaways are the associations tested on the next slide. I would strongly recommend committing
these to memory.
Pneumonia Time
Pneumonia in an immunocompromised patient/HIV patient
Most common cause of walking pneumonia
Pneumonia in an alcoholic
Pneumonia in an alcoholic/obtunded state that is foul smelling
Interstitial pneumonia in a bird handler
Pneumonia in the setting of bats/bat dropping exposure/spelunking/KY-OH Travel Hx
Pneumonia in the setting of a visit to SoCal/NM/W.Texas
Pneumonia associated with Red Currant Jelly Sputum
Pneumonia associated with Rust colored sputum
Pneumonia transmitted via Air Conditioning
Pneumonia in an individual with Q Fever
Pneumonia associated with Cystic Fibrosis/Ventilator patients
Pneumonia associated with hyponatremia (low yield)
3 most common causes of atypical pneumonia
Pneumonia in a neonate with gram +ve coccus staining
Pneumonia in a neonate with gram -ve rod staining
Viral Pneumonia in a kid less than 1 yr old
Pneumonia in a wool sorter/associated with Hemorrhagic Mediastinitis
Most common cause of Pneumonia in a young adult
Most common cause of Pneumonia overall
Most common cause of viral pneumonia
Pneumonia with a lung abscess
Pneumonia in an IV Drug User
Pneumonia associated with Air-Fluid Levels on CXR
Q24
What is the organism that best matches the following info cluster?
-Cellulitis secondary to an infection with an anaerobe
-Gas Gangrene
-Food poisoning
-Produces Alpha toxin
Q24 Key
What is the organism that best matches the following info cluster?
-Cellulitis secondary to an infection with an anaerobe
-Gas Gangrene
-Food poisoning
-Produces Alpha toxin
-Clostridium Perfringens
Q25
What is the organism that best matches the following info cluster?
-Causes Spastic Paralysis
-Prevents the release of GABA/Glycine from inhibitory neurons
-Vaccine Preventable
Q25 Key
What is the organism that best matches the following info cluster?
-Causes Spastic Paralysis
-Prevents the release of GABA/Glycine from inhibitory neurons
-Vaccine Preventable
-Clostridium Tetani (releases Tetanospasmin, classic association with being stung by a
sharp object).
Q26
What is the organism that best matches the following info cluster?
-Toxin prevents release of Acetylcholine
-An adult that bought canned soup from a store
-A baby that consumed honey
Q26 Key
What is the organism that best matches the following info cluster?
-Toxin prevents release of Acetylcholine
-An adult that bought canned soup from a store
-A baby that consumed honey
-Clostridium Botulinum (causes a FLACCID, not SPASTIC paralysis)
Q27
A 23 yo. female presents with abdominal pain and intense diarrhea that started 3 days
ago. Past medical history is unremarkable save for recent treatment for a respiratory
infection that was notable for copious bouts of foul smelling sputum. Empiric
treatment is started with subsequent resolution of her symptoms. The drug of choice
that resolved this womans symptoms is associated with which of the following side
effects?
a.
b.
c.
d.
e.
Aplastic Anemia
Hypersensitivity skin reactions
Sensorineural hearing loss
A metallic taste in the posterior tongue
Diffuse flushing over the entire skin upon IV infusion of the drug
Q27 Key
-The best answer to this question is D
-Her PMH is significant for a lung infection with an anaerobe (foul smelling sputum is
pathognomonic).
-The DOC for treating Anaerobic lung infection is Clindamycin.
-Clindamycin is associated with the HY SE of Pseudomembranous Colitis secondary to
C. Difficile overgrowth.
-The DOC for treating C. Difficile associated Pseudomembranous Colitis is
Metronidazole.
-A HY SE of Metronidazole is a metallic taste in the mouth.
Q28
What is the organism that best matches the following Info Cluster?
-Transmission via exposure to bodies of water containing animal urine.
-?????????? (this is a legit hint btw)
Q28 Key
What is the organism that best matches the following Info Cluster?
-Transmission via exposure to bodies of water containing animal urine.
-?????????? (this is a legit hint btw-think of the question mark as being interrogated)
-Leptospira Interrogans (causing Leptospirosis)
Q29
What is the organism that best matches the following Info cluster?
-No cell wall
-Susceptible to treatment with Erythromycin
-CXR shows diffuse interstitial infiltrates
-Patient has very mild symptoms
Q29 Key
What is the organism that best matches the following Info cluster?
-No cell wall (does not gram stain). Consider this bug if you get an exam question
about a person in their 20s-40s with low grade fevers and a mild headache.
-Susceptible to treatment with Erythromycin
-CXR shows diffuse interstitial infiltrates
-Patient has very mild symptoms
-Mycoplasma Pneumoniae
Q30
What is the organism that best matches the following Info cluster?
-Conjunctivitis in Neonates
-Lymphogranuloma Venereum
-Blindness
-Urethritis and Pelvic Inflammatory Disease
-Could be treated with Doxycycline or a Macrolide
Q31
What is the organism that best matches the following associations?
Diarrhea in an AIDS patient
Pneumonia in an AIDS patient
Meningitis in an AIDS patient
-Fever, Cough, and Night Sweats with cavitation in the upper lobe of the lung
-Rash starts on the palms and soles and migrates centrally
Q31 Key
What is the organism that best matches the following associations?
Diarrhea in an AIDS patient-Cryptosporidium
Pneumonia in an AIDS patient-Pneumocystis Jirovecii
Meningitis in an AIDS patient-Cryptococcus Neoformans
-Fever, Cough, and Night Sweats with cavitation in the upper lobe of the lungMycobacterium Tuberculosis
-Rash starts on the palms and soles and migrates centrally-Rocky Mountain Spotted
Fever (caused by Rickettsia Rickettsii)
Q32-STD Descriptions
Match the following STD buzzwords to the offending organism.
Painless chancre (or ulcer)
Granuloma Inguinale
Epithelial Cells with Inclusion Bodies
Lymphogranuloma Venereum
Genital Warts
Urethral discharge (gram -ve diplococci)
Diagnosis with Darkfield Microscopy
Painless ulcers with no lymph node enlargement
Painful ulcers with bilateral inguinal lymphadenopathy
Painful vesicles on the genitalia
Painless genital ulcer that progresses to massive inguinal lymphadenopathy
Urethral discharge in the setting of septic arthritis
DOC is Doxycycline
DOC is Ceftriaxone
Mycobacterial Species
-Are obligate aerobes, having a predilection for the lung apices.
-Cell wall is rich in mycolic acids which makes it acid fast (the ability to take up
Carbolfuchsin in the Ziehl-Neelsen stain).
-Key members of this bug class to be aware of include M. Tuberculosis, M. Avium
Intracellulare, M. Marinum, M. Kansasii, and M. Leprae.
-You should seriously consider this bug if you get a vignette talking about foreign
countries and constitutional symptoms like Fevers, Night Sweats, Weight loss, and
Hemoptysis (however, when you get to Heme-Onc, substitute the TB thought for
cancer!). Another trigger statement is sputum sample positive for Acid Fast Bacilli.
-TB is destroyed via cell mediated immunity.
The Progression of TB
Viral Basics
-Viruses can be classified in multiple ways-some as DNA and some as RNA Viruses.
-They could also be classified as being double or single stranded viruses.
-The +ve sense viruses have the ability to infect the host cell as they are essentially
mRNA (this is really important!). The -ve sense RNA viruses require an RNA
dependent RNA Polymerase to make the + strand that can infect the cell.
-All RNA viruses are single stranded (except Rotavirus that is double stranded).
-All DNA viruses are double stranded (except Parvovirus B19-transmitted via
respiratory aerosols).
Viral Hooks for The Boards (may not be HY now but is super HY later)
-All DNA viruses are double stranded except Parvo B19.
-All RNA Viruses are single stranded except Rotavirus.
-Any DNA virus ending with the letter A has a circular genome. The others have linear
genomes.
-The only DNA Virus that replicates in the cytoplasm is the Poxvirus (carries its own DNA
Dependent RNA Polymerase).
-All DNA viruses are enveloped with the key exceptions being Parvovirus, Adenovirus, and
Papovaviruses (Polyoma and Papillomaviruses). Others are naked.
-Most DNA viruses get their envelope from the plasma membrane with the exception of
Herpes (gets its envelope from the nucleus).
RNA Viruses-Introduction
RNA Viruses
DNA Viruses
HY DNA Viruses-HPV
-Is a DNA Virus that causes most of the cervical cancer cases in women.
-There are low and high risk HPVs.
-The low risk ones include HPV 6 and 11 which cause genital warts (also known as
Condyloma Acuminata-please do not confuse with Condyloma Lata that is found in what
stage of what disease?).
-The high risk HPVs include HPV 16 and 18 which cause Cervical Cancer. The proteins
implicated in this process are E6 (which inhibits p53) and E7 (which inhibits Rb).
-Rb and p53 are involved in the transition from the G1-S phase.
-In the presence of E6/E7 there is unchecked continuation through the cell cycle even in the
presence of DNA damage with an increased risk of malignancy.
Hepatitis Summary
Q33
A 75yo. man is being evaluated for a 3 day history of productive cough, fever, and
chills. The medical student on service collects some of the patients rust colored
phlegm for evaluation prior to beginning empiric treatment. PE reveals a febrile
patient with a temperature of 103 degrees F and crackles in the right lower posterior
lung field. Which of the following best explains a key virulence factor associated with
the offending organism?
a.
b.
c.
d.
e.
Q33 Key
-The best answer here is D.
-The offending organism is S. Pneumoniae which has an IgA protease.
-The rust-colored sputum is pathognomonic for S. Pneumo (which is a catalase
negative, alpha hemolytic, gram positive diplococcus that grows in chains).
-Not sure how HY this is but Salmon colored Sputum is associated with S. Aureus
pneumonia.
-Treatment with Pneumonia caused by S. Pneumo is typically Penicillin but increasing
resistance has tilted the balance towards Ceftriaxone (which belongs to what
generation of Cephalosporins??)
Fungi Introduction
-Fungi could be grouped as being molds or yeasts.
-Certain fungi function as both molds or yeasts, depending on the surrounding
temperature.
-One unusually HY thing to know about fungi for your exam are the pictures of the
different organisms. They love testing these!
-Most exam questions introduce fungal skin infections by talking about KOH preps.
Candida Albicans-Yeast
-Common colonizer of the skin, GI tract, and female genital tract.
-In the immunocompromised, C. Albicans is associated with oral thrush and
esophagitis (inflammation of the esophagus).
-In females, Candida causes vaginitis (associated with severe itching).
-Candida is also associated with diaper rashes and intertrigo. Strongly consider
intertrigo when a descriptor is given of an obese individual developing rashes under
skin folds. Candida rashes typically have 2 things-Redness with shaggy borders +
smaller surrounding satellite lesions.
-The classic exam Q stem is typically a description of a cottage cheese discharge from
the vagina or a picture of oral thrush OR an AIDS patient complaining of difficulty
with swallowing (esophagitis).
Oral Thrush
Q37
What is the bug that best matches the following info cluster?
-Bird/Pigeon droppings
-Meningitis in an AIDS patient
-Soap bubble appearance on India Ink staining
-DOC is Amphotericin B + Flucytosine
Q37 Key
What is the bug that best matches the following info cluster?
-Bird/Pigeon droppings
-Meningitis in an AIDS patient
-Soap bubble appearance on India Ink staining
-DOC is Amphotericin B + Flucytosine
-Cryptococcus Neoformans (another yeast)
Q38
What is the bug that best matches the following info cluster?
-Atypical/interstitial Pneumonia
-AIDS/Immunocompromised Patient
-Prophylaxis with Trimethoprim-Sulfamethoxazole
-Prophylaxis with a CD4 count < 200
-Cannot be treated with Amphotericin B
Q38 Key
What is the bug that best matches the following info cluster?
-Atypical/interstitial Pneumonia
-AIDS/Immunocompromised Patient
-Prophylaxis with Trimethoprim-Sulfamethoxazole
-Prophylaxis with a CD4 count < 200
-Cannot be treated with Amphotericin B (lacks cell wall Ergosterol)
-Pneumocystis Jirovecii
Q39
What is the bug that best matches the following info cluster?
-Fungus Ball
-Causes invasive infections in immunocompromised individuals
-Causes allergic lower airway infections
-Narrow septate hyphae at acute angles (45 degrees)
-DOC is Voriconazole
Q39 Key
What is the bug that best matches the following info cluster?
-Fungus Ball
-Causes invasive infections in immunocompromised individuals
-Causes allergic lower airway infections
-Narrow septate hyphae at acute angles (45 degrees)
-DOC is Voriconazole
-Aspergillus Fumigatus (a mold)
Q40
What is the bug that best matches the following info cluster?
-Life threatening facial infections
-Diabetics and Immunocompromised patients
-Broad, aseptate hyphae, branching at right angles (90 degrees)
Q40 Key
What is the bug that best matches the following info cluster?
-Life threatening facial infections
-Diabetics and Immunocompromised patients
-Broad, aseptate hyphae, branching at right angles (90 degrees)
-Mucor/Rhizopus species (a mold)
Tinea Versicolor
The Tineas
Dermatophytes spread a host of skin infections including
-Tinea Pedis (Athletes foot)
-Tinea Cruris (Jock Itch)
-Tinea Corporis (generally anywhere on the body, ringworm)
-Tinea Capitis (head)
-Tinea Unguium/Onychomycosis (affects the nails)
-Are commonly treated with topical Terbinafine.
Dimorphic Fungi
-Are famous for assuming 2 forms-a mold form which grows at lower temperatures
AND a yeast form that grows at higher temperatures.
-Memory tool (Mold in the cold, and yeast in the heat).
-For these bugs, be sure to pay attention to geographical locations AND pictures which
are the highest yield testable bits of information.
Q42
What is the bug that best matches the following info cluster?
-Spelunking/going on a cave trip.
-Bird/bat droppings.
-Ohio/Mississippi/KY
-Pulmonary Disease
-Hides in macrophages
Q42 Key
What is the bug that best matches the following info cluster?
-Spelunking/going on a cave trip.
-Bird/bat droppings.
-Ohio/Mississippi/KY
-Pulmonary Disease
-Hides in macrophages
-Histoplasma Capsulatum (remember the other bird connections on your exam like C.
Neoformans with pigeon droppings and Chlamydophila Psittaci with parrots and the
H5N1 bird flu).
Q43
What is the bug that best meets the following info cluster?
-Mississippi/Ohio River Valley
-Pulmonary Infections
-Skin and Bone lesions
-Broad based budding yeast
Q43 Key
What is the bug that best meets the following info cluster?
-Mississippi/Ohio River Valley
-Pulmonary Infections
-Skin and Bone lesions
-Broad based budding yeast
-Blastomyces Dermatitidis
Q44
What is the bug that best matches the following info cluster?
-Spherules
-Pulmonary infections
-Common in Texas/California/SW United States
-Not necessarily a yeast/mold
-Transmission via inhalation from the soil
Q44 Key
What is the bug that best matches the following info cluster?
-Spherules (if you forget everything else about this bug, dont forget this word!)
-Pulmonary infections
-Common in Texas/California/SW United States
-Not necessarily a yeast/mold
-Transmission via inhalation from the soil
-Coccidioides Immitis
Q45
What is the bug that best matches the following description?
-Lives in soil
-Rose gardener pricked by a thorn
-Painless nodules in a single file on the extremities
Q45 Key
What is the bug that best matches the following description?
-Lives in soil
-Rose gardener pricked by a thorn
-Painless nodules in a single file on the extremities
-Sporothrix Schenckii
HY Parasitology
-Entamoeba Histolytica is a common cause of bloody diarrhea as a parasite. It is associated with
liver abscesses. It is transmitted via the fecal-oral route. EH is lytic to the colon.
-Giardia is classically associated with hikers/campers who decide to take the bad decision of
drinking water from a stream. Giardia causes a watery diarrhea that smells really, really, really bad
(due to the presence of fat).
-Cryptosporidium is a common cause of long lasting diarrhea in AIDS patients. A HY method of
transmission for your exam is via unclean water supplies. It is detected by Acid Fast staining of
oocysts on a stool sample (do not knee jerk and pick TB upon mention of acid fastness on your
exam). Do not confuse with Cryptococcus which is a fungus that causes Meningitis in AIDS
patients.
-Trichomonas is a sexually transmitted parasitic infection that is associated with a foul smelling,
gas bubbly, greenish vaginal discharge. A HY association is the physical exam finding of a
Strawberry Cervix.
HY Parasitology-contd.
-Toxoplasma Gondii is a parasite that has domestic cats as its primary host. Consider this
bug in an exam scenario dealing with cat feces/litter in a pregnant woman. T. Gondii is
associated with ring enhancing lesions on MRI.
-Leishmania Donovani is transmitted via the sand fly. This bug causes visceral and
cutaneous infections. Classic Sx triad of Spiking Fevers, Hepatosplenomegaly, and
Pancytopenia (low levels of all blood cells) in Visceral Leishmaniasis. Dx requires finding
amastigotes in macrophages. Cutaneous Leishmaniasis is associated with skin lesions
(ulcers) that take a very long time to heal.
-The DOC in the treatment of Giardia, Entamoeba, and Trichomoniasis is Metronidazole.
Malaria Treatment
-Chloroquine if susceptible.
-Add Primaquine to deal with the dormant Hypnozoites.
-In chloroquine resistance, consider one of 4 options (Doxycycline + Quinine,
Atovaquone + Proguanil, or Artemether + Lumefantrine, OR Mefloquine). These are
quite low yield for your exam.
Worms-General Principles
-Nematodes are Roundworms, Cestodes are Tapeworms, Trematodes are Flukes.
-Enterobius, Ascaris, and Trichinella (EAT) are acquired via Fecal-Oral Transmission.
They are Nematodes.
-Strongyloides, Ancylostoma, and Necator (SAND) are acquired through direct skin
inoculation. These are also Nematodes.
-Many of these bugs take a circuitous route from the lymphatic system to the lungsOropharynx-swallowed-get to the intestine-back to lymphatics-rinse and repeat.
-Many of these bugs are treated with drugs ending in the term Bendazole.
-Focus mostly on the HY history and Characteristics of these bugs.
Disgusting #3-Trichinella
-Acquired primarily by consumption of undercooked meat.
-Consider this bug if you get a question about an individual that
consumed undercooked meat and then had muscle aches and
visual problems (edema behind the orbit).
Stay Tuned...
-HIV to come tomorrow (makes more sense to discuss HIV with Pharmacology).
HY Oncology Review
Some MS2
Objectives/Suggestions
-Oncology is mostly about being able to group things, so you should focus on learning distinguishing
characteristics of the different cancers which are well highlighted in your lecture slides (and in this
document).
-The actual final contains Heme material, so dont blow that off.
-Unfortunately, theres little in the way of rationalization (much unlike Heme) involved with Oncology
so you should do your best in knowing how to identify different diseases by clinical presentation and lab
findings (flow cytometry, translocations).
-In view of this, the goal of this review is twofold-A)To provide you with vignettes detailing how these
different disorders are typically tested and then B)To provide you with summaries of the key features
underlying the different diseases/underlying pharmacology.
-Theres intentional repetition built into these slides to drive certain key points home. In addition,
theres questions admixed with the content to promote active learning. The answers to these questions
are usually on the next slide (and in a few cases, in later slides).
Q1
A 7 month old infant was brought by his parents to the ED with acute complaints of
severe hand pain. PE reveals tender DIPs and PIPs with massive swelling. After the
administration of analgesics to reduce the pain, the physician prescribes a drug that
could potentially decrease future symptoms in the infant. The boys parents recently
immigrated to the US from Nigeria. Which of the following represents the most likely
mechanism of action of the drug that was prescribed by the physician.
a.
b.
c.
d.
e.
Q1 Key
-The best answer is B, Ribonucleotide Reductase.
-The drug in this case is Hydroxyurea, which inhibits Ribonucleotide Reductase.
-Hydroxyurea increases the synthesis of HbF which would hopefully ameliorate future
episodes of dactylitis secondary to sickle cell disease (which this child has).
-This is one of many ways they could integrate Heme material with the material from
Oncology.
Q2
A 67 yo male presents to the Med19 clinic with complaints of fatigue and low energy.
He mentions having frequent episodes of low back pain which has required the
repeated use of Ibuprofen. Lab studies reveal a hematocrit of 36% and a blood calcium
level of 15 g/dL (normal is between 8.5-10.2 g/dL). The most likely finding on a blood
smear obtained from this patient is?
a.
b.
c.
d.
e.
Q2 Key
-The best answer is A.
-The question is a bit nonspecific, but there are several important clues-bone pain
(lytic lesions), fatigue (anemia), high calcium (hypercalcemia), age (in his 60s).
-The most likely diagnosis here is Multiple Myeloma.
-MM is associated with the classic Rouleaux formation on blood smear.
Q3
A 53 yo female presents to the Med19 clinic for her yearly checkup. PE reveals a firm, non tender mass in the
anterolateral neck. During the course of the interview, the patient mentions having low grade fevers over the last 6
months in addition to an unintended 19 Lb weight loss. A tissue biopsy is obtained from the patient with the results
shown below. Increased survival in patients having a similar condition is predicted by?
a.
b.
c.
d.
e.
Q3 Key
-The best answer is E.
-The patient has Hodgkin's Lymphoma, with Reed Sternberg Cells (RS cells) being
pathognomonic.
-HL associated with large titers of lymphocytes (lymphocyte predominant) have an
excellent prognosis.
Q4
A 5 yo boy is brought by his concerned parents to the Med19 clinic with complaints of
fatigue, anorexia, night sweats, and a 15 Lb weight loss over the past 3 weeks. He has
since been walking on a limp with complaints of dull back pain. PE reveals bilateral
conjunctival pallor, hepatosplenomegaly, painless lymphadenopathy, and skin
petechiae. CBC reveals a massive proliferation of blasts with positive staining for
Terminal Deoxynucleotidyl Transferase. The most likely diagnosis in this infant has a
strong association with?
a.
b.
c.
d.
e.
Q5
A 23 yo. woman has experienced low grade fevers, night sweats, and generalized
malaise for the last 2 months. PE reveals non-tender cervical lymphadenopathy. A
Lymph node biopsy reveals CD15/30-/20+ Reed Sternberg cells. The Med19 student on
service assures the patient that her prognosis is excellent, but mentions that there is a
small risk of progression to;
a.
b.
c.
d.
e.
Q5 Key
-The best answer is E.
-This patient has Lymphocyte Predominant Hodgkins Lymphoma.
-Theres a small risk of progression to a Diffuse Large B Cell Lymphoma.
Q6
A 21 yo female presents with symptoms of fatigue and malaise for the past 2 weeks. PE
reveals painful cervical lymphadenopathy with prominent splenomegaly. A lymph
node biopsy reveals extensive hyperplasia of the paracortical zone. A potential sequelae
of this patients illness is the future development of;
a.
b.
c.
d.
e.
Q6 Key
-The best answer here is D.
-A history of painful lymphadenopathy in a young individual is very concerning for
EBV infection. Most instructors dont even give the extra history of a LN biopsy
showing paracortical hyperplasia (note that in some cases, mention would be made of
the presence of atypical lymphocytes on a blood smear).
-EBV infection is known to have a strong association with Burkitts Lymphoma which
is associated with an 8:14 translocation (the MYC oncogene being translocated to the
Immunoglobulin heavy chain locus).
Q7
A 62 yo woman comes for a follow up visit with her oncologist after a previous
consultation for suspicious masses in her breast. Assuming a diagnosis of Stage 3 breast
cancer, an axillary lymph node biopsy obtained from this patient would most likely
reveal;
a. A massive paracortical proliferation of CD68+ cells.
b. A massive paracortical proliferation of CD3+ cells.
c. An expansion of a lymph node region that feeds the efferent arteriole with a
prominence of CD3+ cells.
d. An expansion of a lymph node region that feeds afferent lymphatic vessels with a
prominence of CD68+ cells.
e. An expansion of a lymph node region that feeds the efferent lymphatic vessels
with a prominence of CD68+ cells.
Q7 Key
-The best answer is E.
-This lady has breast cancer which classically drains into axillary lymph nodes.
-Hyperplasia of the medullary sinuses (i.e. the region that feeds efferent lymphatic
vessels) would be the most likely pathologic finding.
-Remember that histiocytes (macrophages that express CD68) are the prominent cells
that populate this area of the lymph node.
Q8
A 53 yo woman presents to her Med19 PCP with complaints of vaginal dryness and
sudden feverish feelings that last for a few hours at a time and then go away. She has
also had 2 compression fractures over the past year. The appropriate agent is
prescribed which leads to a marked reduction in her symptoms over the next few
weeks. The drug administered to this patient most likely works by;
a. Agonizing estrogen receptors in breast and endometrial tissue.
b. Antagonizing estrogen receptors in breast and endometrial tissue.
c. Antagonizing estrogen receptors in the breast and agonizing estrogen receptors in
endometrial tissue.
d. Agonizing estrogen receptors in breast and rectal tissue.
Q8 Key
-The best answer here is B. This lady is most likely experiencing symptoms of
menopause/osteoporosis which are best treated with Raloxifene which is a Selective Estrogen
Receptor Modulator (SERM) that decreases breast/endometrial cancer risk (so Im calling it an
antagonist here) and also slows the progression of osteoporosis. The MOA is not as simplistic as
explained here (will discuss more during the review).
-C is a description of Tamoxifen which is also a SERM that decreases breast cancer risk
(antagonist) but increases endometrial cancer risk (agonist). Tamoxifen is primarily used in
breast cancer treatment/prophylaxis.
-Do not forget male drugs like Finasteride and Dutasteride that are the DOCs in the treatment
of male pattern baldness and BPH. DHT promotes growth of the prostate and the evolution of
male pattern baldness. Finasteride/Dutasteride work by inhibiting 5-Alpha reductase which
converts Testosterone to Dihydrotestosterone (DHT). These drugs are essentially useless in the
prevention/treatment of cancer and in some cases present with deleterious effects.
Class 1-Cytarabine/Gemcitabine
-These are both cytosine analogs that get mistakenly incorporated by DNA Polymerase
into DNA.
-These drugs typically have a 2 or 3 carbon replaced by a group that prevents the next
normal nucleotide from being incorporated. They therefore cause chain termination
and in some cases, double stranded breaks in the DNA.
-In normal DNA replication, phosphates must be added to nucleosides before
incorporation. The same holds true for these drugs, therefore a mutation in the
activating kinase is one key mechanism of resistance. Cancer cells could also be
mutated to where they do not get the actual drug into the cell.
Class 2-MTX/5-FU/HU/6-MP
-Methotrexate (MTX) is an inhibitor of Dihydrofolate Reductase (DHFR) which regenerates reduced
tetrahydrofolate for the conversion of dUMP to dTMP. Folic acid is also required for the synthesis of purines.
Prior to DHFR inhibition, MTX receives multiple glutamates from Polyglutamyl Synthase which could be
mutated, leading to a reduced activation of the drug.
-Since MTX inhibits DHFR, rapidly dividing cells that require the regular synthesis of DNA like leukocytes
are particularly affected by this drug. Rescue from increased toxicity is via the administration of a folinic acid
analog, Leucovorin (a rescuer of LEUkocytes). A HY SE of MTX is Pulmonary Fibrosis (LY now, SHY later).
-5-Fluorouracil (5-FU) acts as a uridine analog which requires initial activation by a kinase. Upon activation, 5FU inhibits Thymidylate Synthase (TS). From the pathway 3 slides ago, it is seen that active THF is required for
dUMP to dTMP conversion by TS. It should therefore make sense that the administration of Leucovorin
increases 5-FU toxicity since youre basically supplying more cofactor. For the future, what is the drug you
learnt about in Micro that works like 5-FU?
-Hydroxyurea (HU) inhibits Ribonucleotide Reductase (RR). RR makes the deoxy form of most nucleotides.
With no deoxy form, DNA synthesis is effectively inhibited.
Alkylating Agents
-Are drugs that work mainly by cross linking DNA strands. These cross links hold the strands tightly together and
prevent DNA replication. Irreparable cross links activate mechanisms that lead to cell death by apoptosis.
-HY Drugs in this category include the Nitrogen Mustards like Cyclophosphamide and Ifosfamide (LY ones include the
mustines and mechlorethamine)AND Platinum Compounds like Cis, Carbo, and Oxaliplatin.
-Cyclophosphamide/Ifosfamide are prodrugs that must be converted to active metabolites in the liver. They both work
by attacking N-7 Guanine residues on DNA. A HY SE of these 2 drugs is Hemorrhagic Cystitis secondary to a free
radical damage inducing agent (Acrolein-a cyclophosphamide metabolite). This is prevented with the drug Mesna.
Cyclophosphamide has a strong association with vomiting.
-Cisplatin has the HY SE of Nephrotoxicity (prevented with Amifostine) and vomiting (emesis). The HY drug to be
aware of in terms of preventing emesis is Ondansetron, which is a 5-HT3 (Serotonin) receptor antagonist. Blocking
Dopamine receptors also relieves emesis.
-It is important to know the progression in susceptibility of blood cells (stem cells-progenitors/blasts-mature cells) to
alkylating agents. Stem cells (express ALDH) are somewhat resistant to all alkylating agents with cyclophosphamide
having zero effect. Blasts/progenitors are utterly destroyed by all these drugs. These drugs have essentially zero effect on
mature cells. ALDH, in a series of steps, oxidizes cyclophosphamide to inactive metabolites.
Special Mention-Rituximab
-Is a chimeric murine IgG monoclonal antibody that binds to CD20 on normal and neoplastic B
lymphocytes.
-From Immunology, we know that IgG and IgM (remember the GM makes classic cars
mnemonic) activate complement. One killing mechanism employed by Rituximab is complement
mediated lysis of cancer cells.
-From Immunology, we know that Macrophages and NK cells possess FC-Gamma receptors that
recognize the constant region of IgG. Rituximab (IgG) when bound to CD20 on a neoplastic cell,
promotes Antibody Dependent Cellular Cytotoxicity (ADCC) which is another killing
mechanism.
-By a poorly understood mechanism, bound Rituximab also induces apoptosis of neoplastic cells.
-It is HY to know that Rituximab does not affect plasma cells (these do not express CD20).
LN Pathologies-Follicular Hyperplasia
-Is a pattern observed with infectious/inflammatory agents that activate B cells.
-These activated B cells migrate to the germinal center and proliferate in response to antigens that
have been presented by Follicular Dendritic cells. These reactive germinal centers also contain
Tingible Body Macrophages which serve more of a garbage clearing role.
-Common inciting agents that are implicated in follicular hyperplasia include Rheumatoid
Arthritis, SLE, Toxoplasmosis, and early HIV infection.
-It is easy to get Follicular Hyperplasia confused with Follicular Lymphoma so key distinguishing
features (that are found only in follicular hyperplasia) include the preservation of the LN
architecture, a variation in the size and shape of germinal centers, and the presence of phagocytic
activity (from tingible body macrophages) in germinal centers (this is HY!).
LN Pathologies-Paracortical/Sinus Hyperplasia
-Caused primarily by immune reactions involving T cells.
-T cells are our bodys primary mechanism for dealing with intracellular organisms.
-Paracortical Hyperplasia is typically encountered in response to viral infections (a HY
virus for your exam is EBV), after vaccinations (smallpox for example), and in certain
drug reactions (like Phenytoin which is an antiepileptic medication).
-Hyperplasia of medullary sinuses is typically observed in situations involving LN
drainage of malignancies. The enlargement arises from the hypertrophy of the
endothelial cells lining the lymphatic sinusoids and a massive infiltrate of
macrophages.
Q9
19 yo college student with splenomegaly. This picture is associated with hyperplasia of what lymph node region?
What is the most likely diagnosis?
Q9 Key
-Acute EBV Infection.
-The age is fairly consistent (young person) with a HY history (splenomegaly).
-Hyperplasia of the Paracortex would be expected in this scenario since this is a viral
infection.
Q10
63 yo female that has felt tired over the last 6 months. PE reveals splenomegaly and axillary lymphadenopathy.
WBC Count is >63000/uL. What is the most likely diagnosis?
Q10 Key
-The most likely diagnosis is CLL.
-The cells in the picture look a lot like lymphocytes.
-The WBC count is high.
-The vignette mentions the presence of lymphadenopathy (raising the possibility of a
lymphoma).
-The patients age is very concerning for CLL (which is the most common
leukemia/lymphoma in this age group). There is a nice smudge cell in the image as
well which should confirm the diagnosis.
Q11
25 yo with a history of recurrent bleeding and multiple hospitalizations for infections over the last 6 weeks. PE
reveals axillary lymphadenopathy and splenomegaly. WBC count > 100k. What is the most likely diagnosis?
Q11 Key
-The most likely diagnosis here is AML.
-The Auer Rods in the image are essentially all you need to clinch the diagnosis.
-Remember that Auer Rods are characteristic of the 15:17 translocation associated with
Acute Promyelocytic Leukemia.
-Treatment of this condition is with ATRA which binds to the defective retinoic acid
receptor and promotes maturation.
Q12
72 yo male with bone pain.
Q12 Key
-This is Multiple Myeloma.
-This should be one of the very first thoughts on your exam with any mention of an
old individual with bone pain.
-Dont forget other HY associations like the M spike on Serum Protein
Electrophoresis, CRAB Symptoms, and Amyloid deposition in different organs (Apple
Green birefringence under polarized light).
Q13
What is the most likely cytoplasmic inclusion associated with this picture?
Q13 Key
-This patient has sickle cell disease.
-Remember the association with a Glutamic Acid to Valine substitution.
-Consider this in an exam question describing a young person with dactylitis.
-Most SCD patients auto infarct their spleens.
-The lack of a spleen is associated with the presence of Howell Jolly bodies on a blood
smear which is the answer to this question.
Q14
A 23 yo who just delivers a baby goes into shock and starts bleeding from multiple orifices. What is the best
screening test in an individual with this condition?
Q14 Key
-This is most likely DIC (Disseminated Intravascular Coagulation).
-The D-Dimer test is one of the screening tests of choice in ruling out DIC.
-The image on the preceding slide shows a few sheared RBCs (Schistocytes).
Q15
What should be expected on flow cytometry studies in an individual with this
condition?
Q15 Key
-These are Reed Sternberg cells which are classic for Hodgkins Lymphoma.
-These cells are CD15/30+.
Q16
65 yo male with painless axillary lymphadenopathy. What should flow cytometry
studies of these cells reveal?
Q16 Key
-Again, this is CLL.
-These cells should be CD5+.
-I dont mean to be annoying with the many CLL questions but CLL should be one of
your top diagnosis in an old male (typically >60).
Q17
In an individual with this condition, what can you say about Ferritin, TIBC/Transferrin, and % Transferrin
Saturation levels? What can you say about the RDW?
Q17 Key
-This person most likely has Fe deficiency anemia.
-Ferritin and % transferrin saturation levels should be low.
-Transferrin/TIBC levels should be high.
-The Red Cell Distribution Width (RDW) should be increased.
HY Triggers
Cancer associated with lymphoblast accumulation
B cell neoplasm with smudge cells on peripheral smear
Cell morphology associated with Hodgkins Lymphoma
Plasma cell tumor
Hypercalcemia, Renal Failure, Anemia, Bone Pain
General class including Follicular, Mantle Cell, and Marginal Zone Lymphomas
Early myeloid lineage neoplasms
Stem cell with ineffective hematopoiesis that replaces bone marrow
Clonal proliferation of a myeloid stem cell giving rise to multiple cell types with 1 type predominating.
8:14 translocation, C-myc activation
14:18 translocation, BCL-2 overexpression
11:14 translocation, Cyclin D overexpression
Neoplasm associated with H. Pylori Infection
Large % of myeloid blasts in the bone marrow
Auer Rods
Bence Jones Proteins in the urine
Philadelphia Chromosome
Acute Leukemias
Please do not depend on these rules, they work really well under certain scenarios but I
would reserve these as more of a last resort measure when trying to answer questions.
NHL-Follicular Lymphoma
-Follicular Lymphomas tend to affect older patients with males and females affected equally.
-The HY cytogenetic abnormality to be aware of here is the 14/18 translocation. The translocated proteins are
BCL-2 which is anti-apoptotic and the Ig Heavy chain gene. We always need to make Igs so the Ig Heavy chain
gene is constitutively expressed. Moving the BCL-2 gene to a gene locus that is heavily transcribed basically
confers immortality to the cell line having that kind of translocation as anti-apoptotic proteins are transcribed
all the time. This is the underlying pathophysiology in Follicular Lymphoma.
-Note that these cells would be CD10/19/20+ since they are all B cells. Immunofluorescence should also reveal
+ve staining for BCL-2 which is not a common finding in germinal center B cells since they need to die in the
process of +ve and -ve selection.
-Follicular Lymphomas in many cases progress to Diffuse Large B cell Lymphomas or Burkitts Lymphoma.
-The underlying histology is basically a lymphoid follicles that is completely covered with circles (of equal size)
which represent the proliferating follicles of B cells that do not want to die.
Follicular Lymphoma
DLBCL
NHL-Burkitts Lymphoma
-Represents a common type of childhood NHL.
-Has 2 subtypes with the Sporadic type being more common in the US with a predilection for the abdomen
AND the Endemic type being more common in Africa with a predilection for the neck. Both are associated with
EBV infection.
-The most common cytogenetic abnormality is a translocation of the MYC gene (on chromosome 8) to the Ig
heavy chain locus (Chromosome 14). As discussed with Follicular Lymphomas, the underlying pathophysiology
involves the over-transcription of a gene that is transcribed less frequently under normal circumstances. MYC is
a gene that encourages cell proliferation so there is a massive proliferation of the affected cells. These cells are
CD10/19/20+ (since they are B cells).
-This is the primary reasoning behind Burkitts Lymphoma being very aggressive.
-The gene involved here does not involve apoptosis, so these rapidly churned out cells eventually die and are
phagocytosed by macrophages found in the LN. This is what differentiates the histology of Burkitts Lymphoma
from the histology of follicular lymphoma with the starry sky appearance that is characteristic of this
neoplasm.
HY Triggers
Blood smear result from spleen auto infarction
DOC in the treatment of a patient with a blood smear showing Auer Rods
MCV low, Ferritin high, TIBC low, % Transferrin saturation low
Biopsy reveals LN architectural effacement with a dense collection of BCL-2+ cells
Low platelets in the setting of anticoagulant treatment
Spontaneous abortion in the setting of anticoagulant treatment.
Hematuria in the setting of RBCs lacking central pallor
Histological finding in the setting of hematuria after Fava beans consumption
Increased bleeding time + Increased PTT + Normal PT
Hematuria in the setting of chemotherapy
CBC changes expected after splenectomy
Blood smear result in the setting of a high MCV + Peripheral Neuropathy
Glutamic Acid to Valine mutation
Glutamic Acid to Lysine mutation
Hx of multiple thrombotic events + Activated Protein C Resistance
2 diseases associated with an abnormal Ristocetin Cofactor Assay
Blood smear result in the setting of an MCV<80 in an individual living in an old apartment
Blood smear reveals bite cells
Blood studies reveal an increase in Hemoglobin A2
Dry tap on BM biopsy
High Ferritin + Low TIBC + High % Transferrin Saturation
Blood smear reveals RBCs stacked like poker chips
HY Triggers Key
Blood smear result from spleen auto infarction-Howell Jolly Bodies.
DOC in the treatment of a patient with a blood smear showing Auer Rods-ATRA.
MCV low, Ferritin high, TIBC low, % Transferrin saturation low-Anemia of Chronic Disease.
Biopsy reveals LN architectural effacement with a dense collection of BCL-2+ cells-Follicular Lymphoma.
Low platelets in the setting of anticoagulant treatment-Heparin Induced Thrombocytopenia.
Spontaneous abortion in the setting of anticoagulant treatment-Warfarin Teratogenicity.
Hematuria in the setting of RBCs lacking central pallor-Hereditary Spherocytosis.
Histological finding in the setting of hematuria after Fava beans consumption-Heinz Bodies.
Increased bleeding time + Increased PTT + Normal PT-Von Willebrand Disease.
Hematuria in the setting of chemotherapy-Cyclo/Ifosfamide induced hemorrhagic cystitis.
CBC changes expected after splenectomy-an increase in platelet count (secondary thrombocytosis).
Blood smear result in the setting of a high MCV + Peripheral Neuropathy-Hypersegmented PMNs.
Glutamic Acid to Valine mutation-Sickle Cell Disease.
Glutamic Acid to Lysine mutation-Hemoglobin C Disease.
Hx of multiple thrombotic events + Activated Protein C Resistance-Factor V Leiden.
2 diseases associated with an abnormal Ristocetin Cofactor Assay-VWD and Bernard Soulier Disease.
Blood smear result in the setting of an MCV<80 in an individual living in an old apartment-Basophilic Stippling/ringed
sideroblasts.
Blood smear reveals bite cells-G6PD deficiency.
Blood studies reveal an increase in Hemoglobin A2-Beta Thal minor.
Dry tap on BM biopsy-Aplastic Anemia.
High Ferritin + Low TIBC + High % Transferrin Saturation-Hemochromatosis.
Blood smear reveals RBCs stacked like poker chips-Multiple Myeloma (Rouleaux formation).
HY Pharmacology Review
Some MS2
A Few Words..
-Pharm/Path look benign but they are one of the very HY courses of
M1 (if not the highest yield)
-The principles/drugs you learn will keep hunting you throughout GTS
(and for the rest of your time in med school/medicine)
-For example, Beta blockers come up in GTS Neuro, GI, Cardio, Renal,
Pulmonary, and even some TIME courses.
-So, learn this material as best as you can.
-Pay particular attention to the BOLDED words.
Drug Development
-Fraught with a few challenges.
-Problems include-associated costs of drug development, very few validated targets,
etc.
-Most drugs target G Protein Coupled receptors
-Theres a shift from the use of Natural Products to the use of Synthetic Analogs.
-There are very few novel drugs approved by the FDA each year (new molecular
entities).
2 Key Definitions
Parasympathetic System-Actions.
Drug Classes
There are 2 general drug classes in ANS
Pharmacology (and all of Pharmacology in general)
-AGONISTS
-ANTAGONISTS
Acetylcholinesterase Inhibition
-Is the turn off mechanism after Acetylcholine secretion.
-With inhibition, ACH persists and hence builds up.
-2 types; Neuronal (more important) and Serum (made by liver).
-Can be inhibited for good purposes as in the treatment of Post-op Ileus (anesthesia
grinds your GI tract to a halt). Remember that ACH makes your GI tract leaky.
-Can be inhibited for bad purposes in the setting of Sarin nerve gas. What should
happen with the increased levels of Acetylcholine? (DUMBBELSS!)
-Clinical Correlate-The Drooling Farmer (Organophosphate poisoning).
Asthmatics/COPD patients
-The biggest problem with Asthma is excessive bronchoconstriction.
-The PSNS loves to bronchoconstrict.
-Blocking the PSNS causes bronchodilation.
-This is accomplished by Ipratropium (used in COPD and Asthma).
-What does the Sympathetic Nervous System do to the bronchus? Through what
receptor?
-What other drug class is used in achieving an Ipratropium like effect?
Key Takeaways
-EAT increases NE release from the presynaptic cell (Ephedrine, Amphetamines, and Tyramine).
Clinical correlate-MAOIs and the Tyramine crisis.
-The primary turnoff mechanism for NE is reuptake.
-Reuptake is blocked by CAT (Cocaine, Amphetamines, and Tricyclic Antidepressants).
-Bretylium and Guanethidine inhibit NE release.
-Epinephrine is not released by neurons. It is a purely endocrine hormone. PNMT is found only
in the Adrenal Medulla.
-The SNS is less specific than the PSNS (why?)
-NE can be broken down by MAO (clinical correlate-MAOIs for depression)
Adrenergic Actions
Alpha-1 Agents
-The SNS is a fight or flight system (so it raises BP and prevents poop/urine formation)
-The major Alpha-1 effect is vasoconstriction so agonizing this should increase total peripheral
resistance and hence increase BP (reduced BV diameter increases resistance to the 4th power).
Alpha-1 is also important in constricting the bladder sphincter and preventing urination.
-Agonizing Alpha-1 can treat hypotension by increasing TPR (Phenylephrine). Constricting blood
vessels also decreases nasal secretions (explains the nasal decongestant Phenylephrine effects).
-Antagonizing Alpha-1 can treat BPH (prostate grows too much and constricts the bladder
sphincter hence promoting urinary retention). A good antagonist is Prazosin.
Alpha-2 agents
-The primary Alpha-2 effect is to decrease SNS outflow by reducing the release of NE
(via negative feedback). With less NE, the Alpha-1 vasoconstrictive and Beta-1 heart
rate increasing effects are abolished (hence BP is lowered). Less NE also somewhat
reduces the pleasurable sensations felt from addictive substances.
-Agonizing these receptors should accomplish all the effects listed above.
-A good agonist is Clonidine.
Beta-1 agents
-The primary beta-1 effect is to increase HR and contractility.
-Agonizing these receptors can help in heart failure/cardiac stress tests. This is the
MOA of Dobutamine and Isoproterenol (Nonselective Beta-1 and 2 agonist)
-Antagonizing these receptors could lower blood pressure by slowing the heart (also
help in Heart Failure) and shutting down the RAAS system (clinical correlate). This is
the MOA of Propranolol.
Beta-2 agents
-The primary Beta-2 effect is to promote bronchodilation and vasodilation.
-Agonizing these receptors is very useful in treating Asthma. This is the MOA of
Albuterol.
-Is there some other drug class that causes bronchodilation?
-Clinical Correlate-Why would Propranolol be contraindicated in an asthmatic? Why
would a beta blocker be contraindicated in a cocaine overdose situation?
A Word on Specials
-Epinephrine is the first line agent in the treatment of
Anaphylaxis.
-Norepinephrine is the first line agent in the treatment of Shock.
-Dopamine is also considered to be a first line agent in the
treatment of shock but is used mostly in special situations.
Matching Game
What would you use in the following conditions?
-Nasal decongestion
-Asthma/COPD
-Shock
-Anaphylaxis
-Substance use withdrawal
-Hypotension
-Hypertension
-Cardiac Stress Tests/Heart Failure
-BPH
-Motion Sickness
-Acetylcholinesterase Inhibitor toxicity (Sarin)
-Open Angle Glaucoma
-Post-Op Ileus
-Gastroparesis
-Vomiting associated with Chemotherapy
PK Practice 1
If a drug is known to be distributed in total body
water, what dose in mg is needed to obtain an initial
plasma level of 5 mg/L in a patient weighing 80 kg
assuming total body water is 60% of his weight?
What is the Q asking for?
Solution
The Q is asking for a loading dose
Loading Dose = Css * Volume of Distribution
VD = 60% of 80 kg = 48 L
LD = 4 mg/L * 48 L = 192 mg.
PK Practice 2
Which statement is correct for Drug X with the following PK elimination parameters?
80-40 mg in 2 hrs, 40-20 mg in 2 hrs, and 20-10 mg in 2 hrs.
a.
b.
c.
d.
e.
Solution
Drug X exhibits first order kinetics.
The half life of the drug is constant regardless of dose.
The amount of drug eliminated will vary based on the starting amount in the blood
stream.
Therefore, E is the best answer.
Re-In zero order elimination, the rate of elimination of the drug is constant, but the
half life of the drug varies (a constant amount of drug is eliminated per unit of time
versus a constant fraction per unit of time in 1st order kinetics).
PK Practice 3
Drug Y has a normal VD of 80L and a clearance of 350 ml/min. If Drug Y was
administered to a patient with 50% renal function, what parameter will differ from
normal?
a.
b.
c.
d.
e.
f.
Solution
With renal dysfunction, the affected variable here will be clearance.
Clearance is found only in the MD equation, not the LD equation. LD is not affected
b/c you need to give the same amount of drug at first to hit a Minimum Effective
Concentration. With clearance impaired, you just need to be a lot more careful with
subsequent doses since the drug hangs around longer.
Therefore the best answer is B
The half life of the drug will increase because less is cleared per unit of time.
The VD will stay constant.
PK Practice 4
At 6 hours after IV administration of bolus dose, the plasma level of a drug is 5 mg/L, If
the VD is 10L and the elimination half life is 3 hours, what was the dose administered?
a.
b.
c.
d.
e.
100 mg
150 mg
180 mg
200 mg
540 mg
Solution
2 half lives have elapsed.
If the current level is 5 mg/L, one half life ago, it must have been 10 mg/L, another one
half life ago, it must have been 20 mg/L.
So the loading dose is equal to the plasma concentration * volume of distribution.
20 mg/L * 10L = 200 mg.
So D is the best answer.
PK Practice 5
An IV Infusion of Hopkinolol is started at 600 mg/hr. If the drug is cleared at a rate of
37.5L in 30 minutes, what is the anticipated plasma level at steady state?
If the levels of Hopkinolol build up to toxic levels of 700 mg in every L of the patients
serum, how long will it take for the drug to be cleared from the body if the half life is 7
hours?
What drug class does Hopkinolol belong to? (N/B-It is not a real drug!)
Clinical Correlate-What is the rescue agent in toxicities of drugs belonging to the
Hopkinolol class?
Solution
The question is asking for a steady state plasma concentration.
MD/Dosing regimen is 600 mg/hr
Clearance is 75L/hr (how did I get this???). Be careful with units.
So CSS = 600 mg/hr / 75L/hr = 8 mg/L.
It will take 28-35 hrs to clear Hopkinolol (a beta-1 selective antagonist) from
circulation (remember the whole 4-5 half lives business?, dont forget it!)
Glucagon is the rescue agent in beta blocker toxicity (why does this make sense?)
Drug Metabolism
Drug Metabolism-Phase 1
-The liver receives most orally absorbed drugs via the portal circulation.
-Theres Phase 1 and 2 metabolism.
-Phase 1 reactions include ROH (remember this functional group?)-Reduction,
Oxidation, and Hydrolysis.
-Phase 1 reactions are undertaken by CYP P450 enzymes which require NADPH as a
cofactor.
-Oxidation reactions are undertaken by Oxidases (can you think of one that operates
at the Adrenergic Synapse?)
-Phase 1 usually produces metabolites that are still active.
Drug Metabolism-Phase 1
-The most important CYP enzyme is CYP3A4.
-The CYP enzyme involved in Alcohol metabolism is CYP2E1.
-CYP2E1 is also involved in the minor metabolism of Acetaminophen.
-CYP2E1 can be induced by the intake of large amounts of alcohol.
-Grapefruit juice is a CYP P450 inhibitor (irreversible) and can cause drug toxicities in
patients taking medications that are metabolized by CYP P450.
-Extensive metabolizers with CYP2D6 mutations can run into trouble when being
treated with Codeine (classic Q stem-sudden death upon initiation of a new drug
regimen for cough).
Acetaminophen Toxicity
Clinical Correlate
The rescue agent in Acetaminophen toxicity is NAcetylcysteine. It is essentially exogenous
Glutathione. This takes care of the NAPQI induced
oxidative stress.
Phase 2 Metabolism
-Are conjugation reactions (add something big to aid excretion)
-Most important reactions are Glucuronidation, Sulfation, and Acetylation.
-Mediated by Transferases.
-Most metabolites are inactive and readily excretable (notable exception is Morphine
which is converted to Morphine-6-Glucuronide by UGT2B7).
-Glucuronosyltransferases require UDP-GA as a cofactor.
-Conjugation with Glutathione requires reduced glutathione (Clinical correlatedrugs eliminated in this way could be harmful in G6PD deficient patients).
Homeopathic Medicine
Final Words
-Pay attention to.
-Pharm is Fun (even if it may not seem like it now).
-Pharm is extremely important for patient care.
-Pharm (in addition to Physiology/Pathology/Microbiology) are HY for all of med
school/future exams/clinical practice.
-Focus on understanding (makes the memorization much easier).
-Understanding Pharm makes you a powerful test taker in med school.
HY Histology Review
Some MS2
Q1
Which of the following best represents the relative abundance of inflammatory cells in
the blood stream (in descending order)?
a.
b.
c.
d.
e.
Neutrophils
-Multilobed Nucleus
-Primary responder in the setting of acute inflammation
-Contain granules that are toxic to bacteria.
-Clinical Correlate-A PMN with much more than 4 lobes on a
blood smear has a strong correlation with B12/Folate deficiency.
Q3
What is the primary function of the following leukocyte after it exits the blood?
a.
b.
c.
d.
Phagocytosis
Histamine release
Collagen Synthesis
Complement Activation
Monocytes
-Kidney/Bean Shaped Nucleus
-Involved primarily in Phagocytosis and Antigen Presentation to T cells
-Called Monocytes in the blood
-Become Macrophages in peripheral tissue with different names
-What are macrophages in the following organs called? (Liver, CNS, Skin, Bone,
Kidneys, Lungs)
-Wall off infection by forming Multinucleated Giant Cells
Macrophage Cells
-Liver (Kupffer)
-Lungs (Alveolar Macrophages-also called dust cells)
-Kidneys (Mesangial Cells)
-Bone (Osteoclasts)
-Skin (Langerhans Cells)
-CNS (Microglia)
Q4
The cells shown at the tip of the arrow are responsible for the bodys defence against?
a.
b.
c.
d.
Fungi
Parasites
Bacteria
Other humans
Eosinophils
-Have a bilobed nucleus
-If you have very pink granules on your exam in a cell that you can pick with your
fingers-think Eosinophils.
-Dont forget the Ddx for Eosinophilia (HY)-NAACP (for your test)
Neoplasm, Asthma, Allergy, Collagen Vascular Disease, Parasites (Helminths via
Major Basic Protein)
For the boards/wards-use DNAAACP (Drugs,Atopic Diseases, Asthma, Addisons
Disease, Collagen Vascular Disease, and Parasites)
Q5
Identify the leukocyte shown in the following image.
a.
b.
c.
d.
e.
Neutrophil
Lymphocyte
Basophil
Eosinophil
Monocyte
Lymphocytes
-Include B/T cells that are part of our Adaptive Immune System and NK cells which
are a part of the Innate Immune System
-B cells differentiate into? (These form antibody factories)
-Can you tell B and T cells apart on histology?
-T cells are involved in cell mediated immunity and Bs are involved in humoral or
blood based immunity
-The cell is essentially filled with the nucleus with a thin rim of cytoplasm around it
Q6
A section of the small intestine is collected on Autopsy of a patient that recently died
of a Cardiac Arrhythmia. PAS +ve organisms were identified in the Lamina Propria of
the patient's bowel. PAS is particularly useful for identifying which of the following
biological materials?
a.
b.
c.
d.
e.
Collagen
Lipids
Nucleic Acids
Sugars
Proteins
Q7
A specimen of a small muscular artery is being examined in the Forensics lab by a
Med19 student. The smooth muscle fibers in the tunica media appear red, and the
collagen bundles in the tunica adventitia appear blue. The slide was most likely colored
using which of the following stains?
a.
b.
c.
d.
Q8
Which of the following types of cartilage or bone is found in the epiphyseal growth
plates of children and adolescents?
a.
b.
c.
d.
e.
Articular Cartilage
Elastic Cartilage
Hyaline Cartilage
Fibrocartilage
Mature bone
Hyaline Cartilage
-Primary skeleton in Embryo
-Bone Precursors
-Cells are Chondrocytes
-Avascular (poor repair)
-Chondroitin Sulfate (attracts water)
-Found in trachea (HY!)
Q9
Which of the following connective tissue cells initiates the mineralization of the bone
matrix during growth and bone remodeling throughout life?
a.
b.
c.
d.
e.
Osteoclasts
Osteocytes
Osteoblasts
Bone lining cells
Osteoprogenitor cells
Q10
Bone obtained from the autopsy of a 99 yo. man is examined by Light Microscopy. ID
the structures indicated by the circles.
a.
b.
c.
d.
e.
Haversian Systems
Haversian Canals
Bony spicules
Canaliculi
Volkmann Canals
Q11
A high magnification bone specimen is obtained from the tibia of a Med19 student. ID the thin lines indicated
by the arrows.
a.
b.
c.
d.
Q12
The following specimen was obtained from the skull of a small infant during a BMT.
Match the structures indicated by the pointers (Arrow, Arrowhead)
a.
b.
c.
d.
e.
Endosteum, Osteoclast
Periosteum, Osteoblast
Osteoid, Osteoblast
Lacuna, Osteocyte
Lamella, Osteoblast
Q13
The multinucleated cells indicated at the tips of the arrows are primarily for;
a.
b.
c.
d.
Bone formation
Bone resorption
Bone mineralization
Bone maturation
Q14
Identify the structures at the tips of the arrows;
a.
b.
c.
d.
e.
Z discs
Intercalated discs
M lines
Intercalated lines
I bands
Q15
A diagnosis of GERD is made in a 50 yo. obese male based on a biopsy of his Esophagus. The tissue seen in this
specimen was obtained from the same biopsy. Which of the following best describes the characteristics of this
tissue type?
a.
b.
c.
d.
e.
Q16
Which of the following best represents the next hierarchy in skeletal muscle
organization following the structure circled in the photomicrograph below?
a.
b.
c.
d.
e.
Myofibril
Myofiber
Z lines
Actin and Myosin
Sarcomeres
Muscle Tissue
-Skeletal (Multinucleated) and Cardiac muscle (1-3 nuclei) are striated.
-Cardiac and Smooth Muscle are under Involuntary (Autonomic Nervous System)
control.
-Skeletal muscle is under somatic control (voluntary), is the largest of all muscle types,
and progresses from Fascicle-Myofiber (actual cell)-myofibril-Sarcomeres-Actin and
Myosin filaments.
-In general, muscle can undergo hypertrophy (cell size increase) but not hyperplasia (#
of cell increase).
Q17
A 45 yo. man presents with small nodules on his hands. A biopsy of the lesion reveals
Basal Cell Carcinoma and adjacent areas of normal skin shown in this image. The area
indicated by the arrows is composed of which of the following tissue types.
a.
b.
c.
d.
e.
Dense Irregular CT
Dense Regular CT
Smooth muscle
Skeletal Muscle
Glandular Epithelium
Follow Up
Which of the following types of connective tissue is found directly beneath the
basophilic surface epithelium in the preceding picture?
a.
b.
c.
d.
e.
Adipose Tissue
Dense Regular Connective Tissue
Elastic Connective Tissue
Loose Connective Tissue
Reticular Connective Tissue
Q18
A 26 yo. female presents to the Med19 free clinic with complaints of myalgias which started 2 days ago. She was
recently placed on Ciprofloxacin as a means of combating an uncomplicated UTI. Which of the following best
describes the tissue type found in the biopsy taken of the patients tendon?
a.
b.
c.
d.
e.
Q19
What is the general function undertaken by the cells indicated at the tips of the
arrows?
a.
b.
c.
d.
Protection
Allows for passive diffusion
Absorption and Excretion
Antibody production
Q20
What is the apical surface modification associated with the following cell type that is
also found in the Duodenum?
Q21
The cells lining this vascular channel demonstrate what kind of epithelial cell
morphology?
Q22
The following biopsy obtained from a patient presenting with complaints of dysphagia
to both solids and liquids demonstrates what kind of epithelial cell morphology?
Q23
If a biopsy of the same organ was taken from a different patient and indicated the
epithelium shown below, what is the term that best describes the underlying
mechanism behind the morphological change observed?
a.
b.
c.
d.
e.
Hyperplasia
Hypertrophy
Dysplasia
Metaplasia
Dyscrasia
Q24
The following biopsy obtained from a patient presenting with signs and symptoms of
painless hematuria demonstrates what kind of epithelial cell morphology?
Epithelial Takeaways
-Q24 is Urothelium (also known as Transitional Cell Epithelium) which lines most of
the GU tract (starting from the calyces of the kidneys).
-Pseudostratified Ciliated Columnar Epithelium are found in the respiratory tract
(possessing what kind of surface modification?) and whip up all the bad things we
inhale.
-Be able to distinguish between cilia (motile/non-motile, locomotory, made of
microtubules) and microvilli (non-motile, absorptive, made of actin).
-Be familiar with the different kinds of Intercellular Junctions (Tight Junctions,
Adherens Junctions, Desmosomes, and Gap junctions-which make up the intercalated
disks of cardiomyocytes).
Q25
What is the general term used to describe the circle as a whole? What are the 3
individual constituents of the circle? Blood from 2 members of the circle ultimately
drain into - through -?
Q25 Key
-Portal Tract/Triad
-Includes Hepatic Artery (O2 rich), Portal Vein (Nutrient Rich), Bile Ducts (simple
cuboidal epithelium)
-Drain through the Sinusoidal Capillaries (lined by what kind of epithelium? What is
special about this epithelium? Is there a basement membrane?)
-Ultimately drain into the Central Vein which returns blood to the IVC through the
Hepatic Vein.
-Dont forget the resident macrophages of the liver (what are they?)
Q26
The cells shown below receive blood from the - side of the cell and secrete bile into the
- side of the cell.
a.
b.
c.
d.
Apical, Basolateral
Lateral, Basolateral
Apical, Basal
Basolateral, Apical
Liver-contd.
-Bile is secreted into the bile canaliculi on the APICAL side of the hepatocyte.
-Bile travels from the HEPATOCYTE to the PORTAL TRACT through the bile
canaliculi (and ultimately to the bile ducts).
-Blood is received from the BASOLATERAL side of the hepatocyte.
-Blood flows from the PORTAL TRACT through the sinusoids towards the
HEPATOCYTE.
-Take note of the distinction in directionality of blood and bile flow (HY!)
Liver Histology
Q27
What is the apical surface modification associated with the cells of the structure shown
below? What does this structure receive flow from? What does this structure drain
into? Outline the pathway of flow through the organ this section was taken from.
Q27 Key
-Microvilli of the Proximal Convoluted Tubule
-Receives ultrafiltrate from Bowmans space
-Drains into the Loop of Henle
Q28
Identify the structure at the tip of the arrow.
Q28
Q29
Identify the structure at the tip of the arrow.
Q29
Is the Transitional
Epithelium of the Bladder
Clinical Correlate
-The Renin Angiotensin Aldosterone system is one of the more important blood
pressure control mechanisms. The Sensor that kicks off this system is the Macula
Densa.
-The Proximal Tubules are the site of action of Parathyroid Hormone in activating the
enzyme that makes active Vitamin D.
-Many BP control medications work at different sites throughout the Nephron.
-Many drugs exert Nephrotoxic side effects by targeting several sections of the
Nephron (classic Q stem-a person being treated for Bipolar Disorder presenting with
signs and symptoms of Polyuria).
Q30
What is the hormone secreted by the cell circled below? What is the hormone secreted
by the other cells? What is the term used to describe the red material?
Parafollicular/Clear Cells/C-cells
-Secrete Calcitonin
-Reduces blood Ca levels (Calcitones down your blood Ca)
-Released in response to high Ca levels in the blood.
-Are clear, large cells found in the thyroid (derived from Neural Crest)
-The thyroid gland contains cuboidal cells in follicles which secrete T3 and T4. These
hormones are stored (bound to thyroglobulin) in the red material known as Colloid.
-The thyroid gland is derived from the thyroglossal duct which descends from the base
of the tongue.
Q31
The following section was most likely obtained from what organ? Identify the layer outlined by the arrow.
HY Lung Factoids
-What is the kind of epithelium found in the trachea?
-What is the apical surface modification found on the epithelium of the trachea?
-What is the diagnostic connective tissue type that differentiates the trachea/bronchi from the bronchioles?
-What are the components of the conducting zone?
-What are the components of the respiratory zone?
-What kind of epithelium is found in the terminal bronchioles?
-What kind of epithelium is found in the respiratory bronchioles?
-What is the specialized cuboidal cell that shows up at irregular intervals within the respiratory zone?
Key
-Pseudostratified Ciliated Columnar Epithelium
-Cilia
-The presence of hyaline cartilage
-Nose, Pharynx, Larynx, Trachea, Bronchi, Terminal Bronchioles.
-Respiratory bronchioles, Alveolar Ducts-Sacs-Alveoli (no smooth muscle here)
-Ciliated Columnar Epithelium
-Cuboidal Epithelium
-Clara Cells
Q32
The image shown below demonstrates what type of cellular adaptive process?
Atrophy
-Is the outgrowth of decreased stress
-Occurs via a decrease in cell size or cell number.
-Occurs in the setting of degenerative disease (Alzheimers) or immobilization
(nursing home).
-Also occurs in menopause/death of nervous tissue/decreased endocrine stimulation.
Q33
The following pathology specimen was obtained post-mortem from an individual that was brought into
the ER with blood pressures of 280/160. What is the adaptive mechanism underlying the change
observed below?
Hypertrophy
-Remember that Cardiac Myocytes are permanent cells.
-They cannot increase in cell number (hyperplasia).
-They can only increase in cell size (hypertrophy).
-Hyperplasia is often observed in response to endocrine stimulation (uterus in
pregnancy-which also undergoes hypertrophy).
-Hypertrophy occurs in the setting of an increased workload-breast (pregnancy),
muscle (exercise, physiologic OR hypertension, pathologic).
Q34
A 60 yo. man presents to the ER with complaints of crushing chest pain. A biopsy of his heart muscle is shown
below? What is the pathologic process indicated by the cells shown on this slide?
Coagulative Necrosis
-Cellular outline is usually preserved (early on).
-Very common in the heart and kidneys.
-Mechanism involved is the loss of blood supply to tissues (i.e in the setting of an
embolus or complete occlusion of a blood vessel).
-When cells die, they spill contents into the circulation. These contents are very
useful in evaluation of disease (for example Troponin in Myocardial Infarction,
AST/ALT in Hepatitis, etc.)
Q35
The change observed below is the sequelae observed in individuals with a long history
of a.
b.
c.
d.
Smoking
Coffee drinking
Alcoholism
Drug abuse
Cellular Adaptations
Acute Inflammation
-Primary cell involved is the Neutrophil (24-48 hrs post-infection)
-With increased vascular permeability, there is the movement of blood into interstitial
spaces. This results in edema.
-Transudate is transparent with low protein(helps you remember that it has a
specific gravity of less than 1.012-mechanism is increased hydrostatic pressure, vessel
wall is mostly intact).
-Exudate is the only option left (SG greater than 1.012-mechanism is increased vascular
permeability, high protein content).
-In addition to histamines, leukotrienes are also responsible for the increased vascular
permeability.
Gram Positives
-Mostly rods (Bacilli), Cocci, or Filamentous Rods.
Key
Top left-Gram Positive Cocci in chains-Streptococcus
Top Right-Gram Positive Rods-Listeria
Bottom Left-Gram Negative Rods-E.Coli
Bottom Right-Gram Negative Cocci-Neisseria
Strep Species
-When you see the words, Gram +ve Diplococci, you should begin to think of S. Pneumo.
-The next best test in the evaluation of a catalase positive organism is its hemolysis pattern on blood agar.
-Alpha hemolysis is partial hemolysis with the colonies appearing green. This is characteristic of S. Pneumo and
S. Viridans.
-Beta Hemolysis is complete hemolysis with a clear zone produced on blood agar. This is characteristic of S.
Pyogenes (GAS) and S. Agalactiae (GBS).
-Please do not think that Group A Strep is Alpha Hemolytic!! (common mistake many make).
-Gamma Hemolysis means no hemolysis and is characteristic of Enterococcus species.
Q1
What is the organism that best fits the following info cluster?
-Vomiting 2-6 hrs after eating potato salad/custard
-Generates a pre-formed toxin that causes a nasty gastroenteritis.
-Beta Hemolytic.
-Gram +ve cocci in clusters.
-Superantigen causes skin sloughing
-Sepsis in a woman leaving super-absorbent tampons in for a few days
Q1 Key
What is the organism that best fits the following info cluster?
-Vomiting 2-6 hrs after eating potato salad/custard
-Generates a pre-formed toxin (which is heat resistant) that causes a nasty
gastroenteritis.
-Beta Hemolytic.
-Gram +ve cocci in clusters.
-Superantigen causes skin sloughing
-Sepsis in a woman leaving super-absorbent tampons in for a few days
-Staphylococcus Aureus.
S. Aureus
-Is a HY bug (know it like you know your name)
-Has Protein A which binds to the constant region of IgG and hence prevents
phagocytosis/opsonization.
-Has the ability to convert fibrinogen to fibrin by virtue of what virulence factor?
-You should definitely know the Superantigens associated with S. Aureus.
-Theres the Exfoliative Toxin that causes Scalded Skin Syndrome.
-Theres also the TSST-1 toxin that causes TSS which is accompanied by massive
hand/sole desquamation (by bridging MHC2 and the V-beta region of the TCR in a
nonspecific fashion)
S. Aureus contd.
-The TSST-1 toxin is strongly associated with leaving a foreign bloody body in for
too long. Classic exam scenarios include Super-Absorbent tampons left in a for a few
days/nasal packing.
-You should seriously consider S. Aureus if you get a question in a person that goes
into sepsis days after covering some internal injury with something made of cotton.
-S. Aureus is gram +ve, so it does not have LPS.
-Note that all Staph toxins are exotoxins. Exotoxins are characteristic of Gram +ves
while Endotoxins (LPS) are characteristic of Gram -ves.
S. Aureus contd.
-Presents in hospitals as MRSA which typically colonizes the nares of hospital workers.
-MRSA is MRSA because it has an altered penicillin binding protein (PBP 2A). This is
the differentiator b/w MSSA and MRSA. It is relatively HY to know the mechanisms of
resistance in select bugs to certain drugs with S. Aureus being one of them.
-Methicillin is resistant to beta-lactamase, so it is not the presence of beta lactamase
that makes MRSA virulent.
-Note that Transpeptidase is an example of a PBP.
S. Aureus contd.
-If you see a question about a person that has the flu and then gets a pneumonia after
the flu goes away, pick S. Aureus as the offending organism. This is important (dont
choose S. Pneumo).
-S. Aureus is also the most common cause of ACUTE bacterial endocarditis. Especially
in a drug user (this is HY!)
Q2
What is the organism that best fits the following Info cluster?
-Endocarditis in a patient with a prosthetic valve
-Produces Biofilm that enables adhesion to indwelling catheters
-Contaminates blood cultures
Q2 Key
What is the organism that best fits the following Info cluster?
-Endocarditis in a patient with a prosthetic valve
-Produces Biofilm that enables adhesion to indwelling catheters
-Contaminates blood cultures
-S. Epidermidis
Q3
What is the organism that best fits the following Info cluster?
-Most common cause of lobar pneumonia in adults/the elderly.
-Gram positive cocci in pairs/lancet shaped
-Most important virulence factor is the capsule
-Pneumolysin causes alpha hemolysis
-Rust colored sputum
Q3 Key
What is the organism that best fits the following Info cluster?
-Most common cause of lobar pneumonia in adults/the elderly.
-Gram positive cocci in pairs/lancet shaped
-Most important virulence factor is the capsule
-Pneumolysin causes alpha hemolysis
-Rust colored sputum
-Streptococcus Pneumoniae
S. Pneumoniae
-How would you detect the capsule of S. Pneumo???
-Produces IgA protease which cleaves IgA and renders it ineffective.
-This is the primary reasoning behind S. Pneumo being a powerful mucosal bug.
-Remember that IgA is the Guardian of the Mucosa.
Q4
What is the organism that best fits the following Info cluster?
-Produces biofilm that enables binding to tooth enamel.
-Common cause of Subacute Endocarditis by binding to fibrin
-Dental Procedures
Q4 Key
What is the organism that best fits the following Info cluster?
-Produces biofilm that enables binding to tooth enamel.
-Common cause of Subacute Endocarditis by binding to fibrin
-Dental Procedures
-Streptococcus Viridans
Q5
What is the organism that best fits the following Info cluster?
-Causes rheumatic fever.
-M protein is very antigenic.
-Child with a beefy red/strawberry tongue.
-Honey crusted lesions on the mouth.
Q5
What is the organism that best fits the following Info cluster?
-Causes rheumatic fever.
-M protein is very antigenic.
-Child with a beefy red/strawberry tongue/Sandpaper Rash (Scarlet Fever)
-Honey crusted lesions on the mouth (Impetigo)
-Streptococcus Pyogenes (GAS)
-Also causes Necrotizing Fasciitis/Cellulitis (leg issues) and Glomerulonephritis in
kids.
Scarlet Fever
Q6
What is the organism that best fits the following Info cluster?
-Intrapartum penicillin given to a pregnant woman with this bug.
-Common cause of neonatal meningitis
Q6 Key
What is the organism that best fits the following Info cluster?
-Intrapartum penicillin given to a pregnant woman with this bug.
-Common cause of neonatal meningitis
-Group B Strep (Streptococcus Agalactiae)
Q7
What is the organism that best fits the following associations?
Reheated Rice
Painless Black Eschar
Edema/Lethal Factor/Protective Antigen
Hemorrhagic Mediastinitis/Widened Mediastinum on CXR
Q7 Key
What is the organism that best fits the following associations?
Reheated Rice-Bacillus Cereus
Painless Black Eschar-Bacillus Anthracis
Edema/Lethal Factor/Protective Antigen-Bacillus Anthracis
Hemorrhagic Mediastinitis/Widened Mediastinum on CXR-Bacillus Anthracis
Q8
What is the organism that best fits the following associations?
Toxin inhibits ACH release/causes flaccid paralysis
Spoiled Canned Goods (Preformed Toxins)
Honey in babies (Spores)
Floppy baby syndrome
Pseudomembranous Colitis
Diarrhea after taking Antibiotics (especially Clindamycin)
Q8 Key
What is the organism that best fits the following associations?
Toxin inhibits ACH release/causes flaccid paralysis-C. Botulinum
Spoiled Canned Goods (Preformed Toxins)-C. Botulinum
Honey in babies (Spores)-C. Botulinum
Floppy baby syndrome-C. Botulinum
Pseudomembranous Colitis-C. Difficile
Diarrhea after taking Antibiotics (especially Clindamycin)-C. Difficile
Q8
What is the organism that best fits the following info cluster?
Tumbling motility
Grows well in the cold (4 degrees)
Granulomatosis Infantisepticum
Nausea/Diarrhea/Fever/Myalgia in a pregnant woman
Beta Hemolytic
Deli Meat/Unpasteurized milk consumption by a pregnant woman
Treat w/Ampicillin
Q8 Key
What is the organism that best fits the following info cluster?
Tumbling motility
Grows well in the cold (4 degrees)
Granulomatosis Infantisepticum
Nausea/Diarrhea/Fever/Myalgia in a pregnant woman
Beta Hemolytic
Treat w/Ampicillin
Deli Meat/Unpasteurized Milk consumption by a pregnant woman
-Listeria Monocytogenes (travels with Actin Rockets)
Neonatal Meningitis
-The most common cause is Group B Strep.
-The second most common cause is E. Coli.
-The 3rd most common cause is Listeria (which is
facultatively intracellular)
Corynebacterium Diphtheriae
-Causes Bulls Neck
-If you get a question about an immigrant with Pseudomembranous Pharyngitis (that
looks grey), you should strongly consider C. Diphtheriae
-The MOA of its exotoxin is the inhibition of protein synthesis (HY)
-Grows as a club shaped/catalase positive rod.
-Transmitted via respiratory secretions.
-Can be prevented with the DTaP vaccine.
-Corynebacterium nukes the heart/the brain (HY)
Gram Negatives
-Best classified as Diplococci, Coccobacilli, and Rods.
-The main Gram -ve Diplococci are Neisseria Meningitidis and Gonorrhea (careful
when you see diplococci on your exam, look for the gram staining pattern first before
picking an answer, dont always knee jerk to S. Pneumo).
-N. Meningitidis/Gonorrhea both ferment glucose. Only N. Meningitidis ferments
maltose.
-In terms of rods, Klebsiella and E. Coli are the big guns. They ferment lactose (i.e. they
grow on Macconkey's agar-pink). A key differentiator is the fact that E. Coli is indole
positive while Klebsiella is not.
Q9
What is the organism that best fits the following info cluster?
-Oxidase +ve
-S/Comma shaped
-Ascending paralysis after infection
-Bloody diarrhea
-Poultry consumption
Q9 Key
What is the organism that best fits the following info cluster?
-Oxidase +ve
-S/Comma shaped
-Ascending paralysis after infection (Guillain Barre)
-Bloody diarrhea
-Poultry consumption
-Campylobacter Jejuni
Q10
What is the organism that best meets the following Info Cluster?
-Polysaccharide Capsule
-Vaccine Preventable
-Hemorrhagic Adrenal Gland Necrosis
-Treat with Ceftriaxone, prophylaxis with Rifampin
-Has a lipo-oligosaccharide
Q10 Key
What is the organism that best meets the following Info Cluster?
-Polysaccharide Capsule
-Vaccine Preventable
-Hemorrhagic Adrenal Gland Necrosis (Waterhouse Friderichsen-very HY!)
-Treat with Ceftriaxone, prophylaxis with Rifampin
-Has a lipo-oligosaccharide
-Neisseria Meningitidis (be suspicious of the words stiff neck/nuchal rigidity on an
exam)
Q11
What is the organism that best meets the following Info Cluster?
-No capsule
-No vaccine
-Pili is a strong virulence factor
-Arthralgias w/Purpura in a young individual (Septic Arthritis)
-Sequelae include Pelvic Inflammatory Disease/Female Infertility
-Treat with Ceftriaxone
Q11 Key
What is the organism that best meets the following Info Cluster?
-No capsule
-No vaccine
-Pili is a strong virulence factor
-Arthralgias w/Purpura in a young individual (Septic Arthritis-very HY!)
-Sequelae include Pelvic Inflammatory Disease/Female Infertility
-Treat with Ceftriaxone
-Neisseria Gonorrhoeae
Q11 Key
What is the organism that best meets the following Info Cluster?
-Aspiration Pneumonia in an alcoholic
-Red currant jelly sputum
-Thick, mucoid colonies
-Empyema/Lung cavitation
Q11 Key
What is the organism that best meets the following Info Cluster?
-Aspiration Pneumonia in an alcoholic
-Red currant jelly sputum
-Thick, mucoid colonies
-Empyema/Lung cavitation
-Klebsiella Pneumoniae (if the sputum is foul smelling, dont pick Klebsiella, pick
Bacteroides or the answer that says anaerobe)
E. Coli
-ETEC causes watery diarrhea that is analogous to that caused by the Cholera toxin.
-ETEC is the most common cause of travelers diarrhea (Montezumas Revenge)
-If you get a question about some guy traveling/going on a vacation and then coming
down with watery diarrhea upon return, you really want to think about ETEC.
-EHEC (O157:H7) produces Shiga Like Toxin and causes bloody diarrhea which is
usually preceded by a watery diarrhea(also characteristic of Shigella, inactivates the
60S ribosomal subunit). EHEC also causes Hemolytic Uremic Syndrome.
-Note that Shigella invades the intestinal mucosa but EHEC does not.
Q12
What is the organism that is best associated with the following Info cluster?
-Infections in Diabetics
-Otitis Externa
-Hot tub folliculitis (ear/skin infection in a swimmer)
-Drug of Choice is Ticarcillin/Piperacillin with Tazobactam
-Produces a blue green pigment (Pyocyanin)
-Grape like Odor
-Ecthyma Gangrenosum
Q13
What is the organism that is best associated with the following Info cluster?
-Watery Diarrhea
-Treat with fluid/electrolyte replacement
-Toxin causes increased cAMP activation
-Diarrhea with Rice-Water Stools
Q13 Key
What is the organism that is best associated with the following Info cluster?
-Watery Diarrhea
-Treat with fluid/electrolyte replacement
-Toxin causes increased cAMP activation
-Diarrhea with Rice-Water Stools
-Vibrio Cholerae
Q14
What is the organism that is best described by the following Info cluster?
-Non-bloody diarrhea
-Pork consumption
-Diarrhea associated with Appendicitis like pain?
Q14 Key
What is the organism that is best described by the following Info cluster?
-Non-bloody diarrhea
-Pork consumption
-Diarrhea associated with Appendicitis like pain?
-Yersinia Enterocolitica
Chlamydia
Antibiotics Introduction
-The Minimum Inhibitory Concentration is the lowest concentration of drug needed to inhibit bacterial growth.
Is a bacteriostatic drug term.
-The Minimum Bactericidal Concentration is the lowest concentration of drug needed to kill 99.9% of bacteria.
Is a bactericidal drug term.
-Bacteriostatic Drugs are good for immunocompetent people. It slows the rate of bacterial growth which gives
the immune system time to kill the bug.
-Bactericidal Drugs are good for immunocompromised people. It kills off the bug completely (since their
immune systems are weak).
-Combination Therapy is typically given with Antibiotics to decrease resistance AND to achieve synergism (1+1
= 3).
Ribosome Inhibitors
For the sake of time
-Know which is 30S and 50S
-Know the mechanism of action of each
-Know the side effects of aminoglycosides, tetracyclines, chloramphenicol (mentioned
earlier).
-Know which is bactericidal and which is bacteriostatic.