Tabes Dorsalis

• This is a manifestation of tertiary (late) syphilis called neurosyphilis
• caused by infection with treponema pallidum, a spirochete
• tertiary syphilis also turns the vasa vasora (blood vessels that supply other blood vessels, eg aortic root) into a bunch of granulomas →:
• Aortic regurgitation – know how to recognize!
• Diastolic decrescendo murmur heard best along the left sternal border
• Aneurysm of the ascending aorta
• Note that tabes dorsalis only affects the dorsal horns.
• This patient had a positive (+ve) Rhomberg's sign
• Rhobmerg's sign
• Patient's balance is fine with his eyes open
• Visual input supplies spatial awareness/proprioception
• Upon closing his eyes the pt sways
• loss of proprioception from dorsal column

(If patient is swaying with eyes open and closed, this is likely a lesion in the cerebellum or vestibular system (eg. CN VIII) and would NOT qualify as a +ve Rhomberg's sign)

• Can you guess the level from which this spinal cord section was taken

A) C1
B) C4
C) T4
D) L4
E) S1

Answer posted on 4/2/07

Note the lateral horns (sometimes called intermediolateral cell column):
(I have circled the right one and have drawn an arrow to the left one)
This area of white matter contains preganglionic sympathetics which arise from the hypothalamus and will synapse onto a postganglionic sympathetic fiber in the paravertebral (aka chain) ganglion. Question for you... would the neurotransmitter used here be
a) norepinephrine (Norepi)
b) epinephrine (Epi)
c) acetylcholine (ACh)
d) glycine (Gly)
e) glutamate (Glu)
f) seratonin (5-HT)

Answer is c) Ach
Remember, all preganglionic autonomic fibers use ACh
Epinephrine is released from the adrenal medulla when preganglionic sympathetic fibers release ACh onto it.

Now, back to the level of the spinal cord:
Since we are talking about sympathetic (aka thoraco-lumbar) outflow, you should know right away that this slide must therefore have been sliced from somewhere between T1-L2.
Knowing this would have gotten you the right answer to my question.

If the question writer is out for your blood he may ask you to distinguish between 2 choices within the range of the lateral horn. Notice the shape of the above section. Now compare it to an upper lumbar section. See the difference? The lumbar section has only one dorsal column and it is just a lot more round. That "just a lot more round" part (I bet) is enough to differentiate for purposes of the exam. But feel free to knock yourself out, I know I did.

Molecular Mechanisms of Apoptosis

Apoptosis is HY for the USMLE Step 1. Here is my attempt to illustrate the molecular basis of apoptosis summarized from Robins.

Urea Cycle

• Urea contains 2 molecules of nitrogen derived from:
• NH3
• **Aspartate**
• Carbamoyl phosphate synthetase is the rate limiting enzyme
• located in the mitochondria
• activated by N-acetylglutamate

Epstein Barr Virus

• Attaches and activates B-lymphocytes CD21 (CR2) receptor
• These activated B cells promotes T cell proliferation
• The effected B-lymphocytes are NOT what are detected by the monospot test.
• Atypical lymphocytes (“Downy Cells”)
• Detected by the monospot test
• AKA (heterophile antibody test)
• Are CD8⁺ T lymphocytes
• Associated with:
• Heterophile positive infectious mononucleolus
• Burkitt's Lymphoma
• Nasopharyngeal Carcinoma
• Structure
• a "HAPPy" double-stranded linear DNA virus (see First Aid virus section)
  

Glucagon for Beta Blocker Overdose

Here's a great board question that I don't know if its ever been asked, but can you think why you would want to give glucagon for a beta blocker overdose? Hint: It’s all about cAMP

• Beta blockers at toxic doses would dangerously ↓ HR.
• The heart has β1 receptors which act through a G_s to raise intracellular cAMP
• Glucagon, via its own receptor can ↑ cAMP independently of the blocked β1 receptor
• Also note, that this is an example of physiologic antagonism
• Giving a β1 agonist to overcome the β-block would be an example of competitive antagonism

Can you say, "Gunner Level?"

2nd Messangers

bangledoc writes:

Thanks miky.It will hep greatly every one taking step 1.
could u write more about other 2nd messenger with application (as cGMP).As this are highly asked in exam.
Thanks again

I agree, 2nd messengers are very HY and therefore should be in any blog called HY for the USMLE


Lets start with this:

For the USMLE Step 1, it is more important to understand how each different 2nd messenger system works individually then to memorize if alpha 1 is a cAMP or cGMP or Gs or Gi. It happens to be cAMP and Gs.

I overlooked this point and placed greater emphasis on which receptor goes with which 2nd messenger system. The basic mnemonics in First Aid should suffice for the exam but there is a little more I would add, and since it is so late it will have to wait for tomorrow. (It involves the regulatory subunits of protein kinase A)

I also have a drawing to help you remember Gq, though I admit its corney!

Hypomagnesemia and PTH

One point which gets you an easy point but otherwise easy to miss is that hypomagnesemia can cause hypocalcemia since magnesium is necessary for the production of PTH.

	PTH	Calcium	Phosphate	Si/sx
Primary Hyperparathyroidism	↑	↑	↓	stones, bones, abdominal groans and psychic moans"
Chronic Renal Failure (→Vit D def.)	↑	↓	↑ - can’t be excreted
Hypercalcemia (malignancy)	↓	↑	↑
Hypomagnesemia	↓	↓	↓	Hypocalcemia that responds to Mg 2+ infusion

Cyanide Toxicity

• Causes
• Infusion with Nitroprusside
• Smoke Inhalation (MCC)
• Combustion of polyurathane (found in mattresses – just look at the tag)
• Effects
• Inhibits cytochrome oxidase (cytochrome a/a3) of the electron transport chain
• NOT cytochrome C (commonly mistaken)
• Blocks the use of oxygen → tissue hypoxia and rapid death
• Si/Sx
• Bitter almond-scented breath
• Agonal respiration
• Nausea and headache
• Treatment
• Amyl and Sodium Nitrite
• Produces methemoglobin (met-HB)
• note: nitrates used for anginal therapy do not cause formation of cy
• Met-HB sucks up CN from the mitochondria
• Iron in met-HB (Fe3+) has stronger affinity for CN than does cytochrome oxidase’s iron
• Results in formation of cyanomethemoglobin
• Sodium Thiosulfate
• Converts cyanomethemoglobin into:
• Thiocyanate
• less toxic & easier to excrete than cyanomethemoglobin
• Methemoglobin
• Methemoglobinemia is treated with methylene blue

cGMP is High Yield

• Know that the drugs acting via cGMP are
• Nitrates (Nitroglycerin, isosorbide dinitrate)
• Increases production of cGMP
• Activation (denitration) to NO occurs within the smooth muscle cells enwrapped around vascular endothelium.
• NO activates guanylyl cyclase → ↑cGMP → dephosphorylates myosin light chain kinase → smooth muscle relaxation
• Note, tolerance develops rapidly
• Addressed by telling pt to take a break from the particular drug or Rx w/ a different anginal drug
• Occupation exposure → Monday Disease
• Nitroprusside
• Rx: Hypertensive emergencies
• Same mechanism as nitrates
• AE: Cyanide toxicity (rx: sodium thiosulfate)
• Sildenafil
• Decreased breakdown of cGMP
• Inhibits 5’-phosphodiesterase
• The enzyme that breaksdown cGMP
• Do not give a pt on a nitrate sildenafil (will synergistically cause their diastolic BP to fall through the floor!)
• Instead give Alprostadil
• If you accidentally did combine the 2 above what drug would you want to give?
• α-1 agonist
• Hydralazine
• dilates arterioles more than veins= reduces afterload; AE: SLE like syndrome
• Know that ANP (Atrial Natriuretic Peptide) acts by activating guanylyl cyclase