5/19 UWorld

Question 1

Describe how ethylene glycol affects the kidneys

Answer 1

• Ethylene glycol (anti-freeze) is absorbed from the GI tract and metabolized into glycolic acid (toxic to renal tubules - acute tubular necrosis) and oxalic acid (calcium oxalate cyrstals)

Question 2

What is the function of the protein produced by Staph Aureus

Answer 2

Protein A is a component of Staph cell wall

It binds antibodies at Fc region, preventing complement from binding, and thus preventing opsinization and phagocytosis

Question 3

Describe the defect causing mitochondrial myopathy

Answer 3

o Maternal inheritance only from mitochondrial DNA

o Without properly functioning mitochondria, cells cannot use oxidative phosphorylation to produce ATP

o Brain and skeletal muscle will be affected first due to high metabolic demand

Question 4

Classic presentation and hallmark finding in mitochondrial myopathy

Answer 4

o Presentation:

§ Myopathy (muscle weakness, myalgia)

§ Lactic acidosis (due to impaired aerobic glycolysis)

§ Nervous system dysfunction (neuropathy, seizures)

§ ***Muscle biopsy shows ragged red fibers (due to accumulation of diseased mitochondria)

Question 5

Describe the funciton of IFN-a and IFN-b

Answer 5

• Secreted by virally-infected cells
• Act locally on uninfected cells to prime them for viral defense
• Bind to receptors in infected and neighboring cells, causing transcription of antiviral enzymes capable of halting protein synthesis

Question 6

Describe how the enzymes transcribed by IFN-a and IFN-b to halt protein transcription only work on infected cells and not uninfected cells

Answer 6

These enzymes are only active in the presence of double stranded RNA, which forms in infected cells as a result of viral replication

So normal protein synthesis can still occur in uninfected cells and is selectively inhibited in virally infected cells

Question 7

What is the MOA of statins

Answer 7

• Statins inhibit HMG CoA reductase, and thus prevent endogenous cholesterol production
• In response to decreased hepatic cholesterol synthesis, hepatocytes will increase LDL receptor expression on their surface, thus clearing LDL from circulation

Question 8

MOA of Cholestyramine

Answer 8

Sketchy - Cho”lobster”amine

• Is a bile acid resin that bind bile acids in the intestinal lumen and prevent recycling of bile acids back to the liver
• The bind to bile acids and then bring them to the colon to be excreted
• Because there is a decrease in bile acids, the liver must promote synthesis of new bile acids (derived from cholesterol), depleting the liver cholesterol stores
• Liver will compensate by upregulating expression of LDL receptors, thus drawing LDL out of circulation

Question 9

MOA of Ezetimibe

Answer 9

Sketchy = Z-shaped eel

Binds cholesterol in the GI tract, preventing their absorption (vs. Cholestyramine which binds bile acids)

Question 10

MOA of fibrates

Answer 10

Sketchy = Gemfibrozil jellyfish

• Decreases serum VLDL (35-50%) and decreased triglycerides by activating PPAR-alpha at liver and peripheral tissues
• When activated, PPAR-alpha upregulates LPL at extra-hepatic sites
• This means increased hydrolysis of chylomicron and VLDL TG’s at peripheral tissues – aka decreased serum TGs

Question 11

MOA of niacin

Answer 11

Sketchy = Lock Niacin monster

• Mechanism of action:
  
  • Unknown
  • Raises HDL (30%)
    
    • Most effective drug for increasing serum HDL
    • Decreases HDL cholesterol transfer and delaying HDL clearance
  • Decreases VLDL, and thus decreased TG

Question 12

MOA of fish oil

Answer 12

• Lowers TG by decreasing production of VLDL and Apo-B

Question 13

• What is the drug of choice for anaerobic bacteria above the diaphragm vs. below the diaphragm

Answer 13

• Above = Clindamycin
• Below = Metronidazole

Question 14

What are Nissl substances and where are they found

Answer 14

Nissl substances are found within RER of neurons

Seen in cell bodies and dendrites

Not in axons - axons do not contain RER

Question 15

Describe the histopathologic changes seen in acute neuronal injury (red neuron)

Answer 15

• Due to transient severe insult that leads to cell death
• Histopathologic changes:
  
  • Shrinkage of cell body
  • Pyknosis of the nucleus
  • Loss of Nissl substance
  • Eosinophilic cytoplasm

Question 16

Describe the histopathologic changes seen in axonal regeneration

Answer 16

• Enlargement of cell body
• Eccentric nucleus
• Enlargement of the nucleolus
• Dispersion of Nissl substance

Question 17

Describe the histopatholic changes seen in neuronal atrophy

Answer 17

• Due to progressive degenerative disease
• Histopathologic changes:
  
  • Loss of neurons and functional groups of neurons
  • Reactive gliosis

Question 18

Review rule of 4’s

Question 19

What is the cause and effect of reperfusion injury

Answer 19

• Occurs when blood flow is returned to an ischemic area, causing increased killing of cells
• Due to:
  
  • Oxygen free radical generation
  • Severe, irreversible mitochondrial damage described as “mitochondrial permeability transition”
  • Inflammation, which attracts neutrophils that cause additional injury
  • Activation of complement pathway
• Leads to cell membrane damage

Question 20

What is a common cause of isolated systolic HTN

Answer 20

Age-related increased arterial stiffening leading to decreased compliance of aorta and other major arteries

Question 21

What apolipoprotein increases risk for Alzheimer’s and which decreases risk

Answer 21

ApoE2 decreases risk

ApoE4 increases risk

Question 22

In what tumor do you see pseudopallisading cell arrangement

Answer 22

Glioblastoma multiforme

Tumor surrounding central necrosis

THINK:

• Pseudopallisading looks like a star = astrocyte
• Central area is necrotic/dead so this must be an old people tumor – astocyte tumor of adults = glioblastoma multiforme

Question 23

What CNS tumor do you see fried egg apperance?

Answer 23

Oligendroglioma

Question 24

What CNS tumor do you see Rosenthal fibers?

Answer 24

Pilocytic astrocytoma

Rosenthal fibers = eosinophilic corkscrew fibers

THINK: Chris Rossman putting the star (astrocytes) on the top of a child’s (tumor of children) christmas tree, so it has a swirly base (corkscrew fibers)

Question 25

What CNS tumor do you see Homer Wright rosettes

Answer 25

Medulloblastoma Homer Wright rosettes (small blue cells wraped around pink areas of neuritic processses) * THINK: Homer Simpson is dumb like a kid (tumor of children); it seems like he lost actual brain cell, neurons (tumor of neurons)

Question 26

In what CNS tumor do you see perivascular pseudorosettes?

Answer 26

Ependymoma Perivascular pseudorosettes - tumor cells surrounding vessel THINK: Ependymoma = tumor surrounding ventricles; ventricles are open spaces containing body fluids; pseudorosettes is surrounding a vessel which contains body fluids

Question 27

Describe the pathophysiology of exophthalmos in Graves disease

Answer 27

* Lymphocytes infiltrate the orbital tissues and secrete cytokines that stimulate fibroblasts to secrete increasing amounts of glycosaminoglycan ground substance such as hyaluronic acid. This increased hyaluronic acid draws water into the orbit resulting in extraocular muscle edema. Combined with interstitial edema, this process pushes the globe outward (proptosis). A sensation of grittiness and excessive tearing occur because the lids are now unable to completely cover the proptotic globe. Desiccation and keratitis may result

Question 28

What is the treatment for exophthalmos in Graves disease

Answer 28

* Treated with glucocorticoids * Antithyroid drugs to do not have a direct effect on ophthalmopathy

Question 29

What are the most common viral causes of meningitis

Answer 29

* Enterovirus (most common) – Coxsackievirus, Echovirus, Poliovirus * Arbovirus * Herpes simplex virus type 2

Question 30

What are the most common bacterial causes of meningitis

Answer 30

* Adults: * Strep pneumoniae * Neisseria meningitides * Neonates: * Group B strep * Gram negative bacilli

Question 31

Differentiate between CSF in bacterial vs. viral meningitis (glucose, protein, WBC)

Answer 31

* Viral: * WBC \< 500 * Lymphocytic predominance * Glucose normal or slightly slow * Protein \< 150 (less elevated that in bacterial) * No organisms on gram stain and culture * Bacterial: * WBC \> 1000 * Neutrophlic predominance * Glucose \< 46 * Protein \> 250 * Gram stain positive

Question 32

What characteristic of viruses allows them to undergo rapid genetic shift?

Answer 32

Segmentation

Question 33

What are the segmented viruses?

Answer 33

* There are 4 segmented viruses - BOAR * Bunyavirus (3 segments) * Orthomyxo (8 segments) * Arenavirus (2 segments) * Rheovirus (11 segments)

Question 34

What are the watershed areas of the colon

Answer 34

Splenic flexure (b/w SMA and IMA) Rectosigmoid junction (b/w sigmoid artery and superior rectal)

Question 35

Describe the pathway (enzymes and substrates) of catecholamine synthesis

Answer 35

Question 36

What part of the catecholamine synthesis pathway is affected by cortisol?

Answer 36

Norepinephrine to Epinephrine via Phenylethanolamine-N-methyltransferase (PNMT)

Question 37

How does pregnancy effect levels of thyroid hormone

Answer 37

Pregnancy cause increased thryoxine-binding globulin (TBG) --\> high total thyroid hormone levels but low free hormone Patient will be euthyroid with normal TSH

Question 38

What are the cartilage, muscle, and nerve derivates of the branchial arches?

Answer 38

* 1^st arch * Cartilage: * Maxillary process, mandibular process, incus, malleus * Muscles: * Muscles of mastication, mylohyoid, tensor tympani, tensor veli palatine * Nerves: * CN V2 and V3 * 2^nd arch * Cartilage: * Stapes, styloid, stylohyoid * Muscles: * Muscles of facial expression * Stapedius, stylohyoid * Nerves: * CN VII * 3^rd arch * Cartilage: * Greater horn of hyoid * Muscles: * Stylopharyngeus * Nerves: * CN IX * 4th-6^th * Cartilage * Arytenoids, cricoid, thyroid * Muscles: * 4^th à Cricothyroid, most pharyngeal constrictors, levator veli palatini * 6^th à All laryngeal muscles except cricothyroid * Nerves: * 4^th à CN X superior laryngeal branch (swallowing) * 6^th à CN X recurrent laryngeal branch (speaking)

Question 39

What is the difference between proteins produced by free ribosomes vs. proteins produced by ribosomes attached to RER

Answer 39

Free ribosomes - translate proteins found in the cytosol Attached ribosomes - translate proteins meant for the cell membrane and meant to be excreted into extracellular space

Question 40

What medication can be used for acute treatment of agitation and psychosis associated with delirium

Answer 40

Haloperidol

Question 41

What is the cause of "wet, wacky, wobbly"

Answer 41

* Normal pressure hydrocephalus * Ventricular dilation with normal ICP * Occurs in the elderly * Triad - “Wet, wacky, wobbly” * Urinary incontinence - wet * Dementia - wacky * Ataxia - wobbly * Magnetic gait – feet appear stuck on floor

Question 42

What are the complications/presentation seen in congenital hydrocephalus

Answer 42

* Macrocephaly * Bulging fontanelle * Poor feeding * Developmental delay * Spasticity and hyperreflexia (due to UMN injury caused by stretching of periventricular pyramidal tracts) * Seizures

Question 43

What antibody will differ the most between patients given IM inactivated polio vaccine vs. oral live attenuated polio vaccine

Answer 43

Duodenal luminal IgA (aka mucosal IgA)

Question 44

Presentation of serotonin syndrome

Answer 44

§ Autonomic instability (hyperthermia, hypertension, tachycardia) § Altered mental status (agitation, confusion) § Neuromuscular irritability (tremor, hyperreflexia, myoclonus) § GI symptoms

Question 45

Antibiotic associated with serotonin syndrome

Answer 45

Linezolid MOA - inihibits 50S ribosomal subunit Also has MAOI action

Question 46

Lesions to what brain lobe affect personality?

Answer 46

Frontal lobe

Question 47

Differences between lesions in the right vs. left frontal lobe

Answer 47

* Frontal lobe * Deficits in executive functioning, concentration, orientation, judgment, personality * Left sided lesions – associated with apathy and depression * Right sided lesions – associated with disinhibited behavior

Question 48

Lesion to what brain lobe will cause hemispatial neglect?

Answer 48

Non-dominant parietal cortex (usually R-side)

Question 49

What are the effects of a lesion to the dominant parietal lobe?

Answer 49

* Gerstmann syndrome = agraphia (inability to write), acalculia (inability to calculate), finger agnosia (inability to distinguish fingers), left-right disorientation