Vitamin K is High Yield for the USMLE Step 1

• Vit. K is needed for the γ-carboxylation of clotting factors 2, 7, 9 and 10
• This gives them a Ca binding site
• This explains why the vit. K dependent factors are the same factors that are dependent on calcium
• Deficiency:

o Primary problem is an inability to γ-carboxylate factors 2, 7, 9 and 10

• therefore, factors ARE made but can NOT be activated by Ca
• Involves several factors, including factor 7 which:
• has the shortest t½ of all the clotting factors
• therefore, factor 7 is the first factor unable to be activated
• Since factor 7 is specific to the extrinsic pathway the extrinsic pathway is affected first
• Since the prothrombin time (PT) is a measure of the extrinsic pathway, it is the value expected to be elevated first
• Leads to ↑↑PT (AND eventually ↑PTT) – therefore, PT is most sensitive since its ↑’d 1^st
• Bleeding time, a measure of platelet function, is normal since platelets are not affected
• Deficiency can be seen in the following patients:
• Newborns born at home
• Breast milk has low levels of vit K
• All babies in the US are given vit. K shots @ birth in the hospital to prevent hemorrhagic disease of the newborn
• Pts on broad spectrum antibiotics
• Bacteria in colon synthesize much of our vit. K
• Pts w/ steatorrhea
• Loss of fat in the stools also leads to a loss of the fat soluble vitamins, including vit. K
• Vitamin E toxicity
• Inhibits vitamin K dependent carboxylation of clotting factors
• Treatment
• Vitamin K Injection
• If bleeding is serious then give fresh frozen plasma

Testable Anemias That Do Not Always Make It To The Books

Here are some anemias that aren't always thought of in the same breath as many other anemias.

• Vitamin C deficiency - since vitamin C enhances non-heme iron absorption in the gut, a vitamin C deficiency can cause a iron deficiency (microcytic and hypochromic) anemia.
• Vitamin E (alpha-tocopherol) deficiency - Vit. E prevents the peroxidation of lipid cell membranes by free oxygen radicals since vit. E is an anti-oxidant. When deficient in vit. E, one sign is acanthocytes in the peripheral blood smear. When these spiny RBCs burst it causes a hemolytic anemia
  
• Similarly, in abetalipoprotinemia, an autosomal recessive disorder of lipid absorption may manifest with acanthocytosis in part because vitamin E (a fat soluble vitamin) is also not being absorbed.
• Orotic Aciduria - megaloblastic anemia unresponsive to folate or B12. A number of wordy enzymes may be deficient but the essential problem here is pyrimidine synthesis and so DNA synthesis is subsequently impaired.
  
• This is very similar to B12 and folate deficiencies since in both of these cases, DNA synthesis is also impaired.
  

Lymphatic Drainage is High Yield for the USMLE

Here's some basic information about lymphatic drainage:


Pretty simple, which is how I like it. Apo B48 is on chylomicrons which carry the dietary lipids. I remember this by its the apolipoprotein that is in the food before (B4) you ate (8). Okay, its not really before you ate it its after you ate it, but I think it gets the point across that ApoB48 is for the lipids that you eat and so is therefore found on chylomicrons. Since lipid soluble vitamins are absorbed with your dietary lipids, chylomicrons also contain fat soluble vitamins.

The right lymphatic duct also drains into venous blood but instead of the left internal jugular/subclavian vein, its into the right ones.

So it was just a quick doodle and explanation today about these straight forward points. I'm sure you can think of a lot of other integrated info about lymphatic system which I encourage you to share in the comments section.

Thiamine is HY for the USMLE Step 1

THIAMINE aka Vitamin B1

Active form: Thiamine Pyrophosphate (TPP)

Main reactions in which thiamine is a cofactor:
These dehydrogenase reactions generate NADH in the mitochondria which enter the electron transport chain to generate ATP, therefore the patient has a problem making ATP.

Cofactors required by the above 2 enzymes are
Thiamine
Lipoic acid
CO2
Folate
NAD+
Which can be remembered by the phrase, "Tender Love and Care for Nancy"

(Thiamine is also a cofactor for transketolase which catalyzes 2 Carbon transfers in the HMP shunt (pentose phosphate pathway) - required to make Ribose 5 phosphate for nucleotide synthesis)

Classic patient is a Malnourished Alcoholic

Signs and symptoms of deficiency:

Wernicke's Encephalopathy

• Peripheral neuropathy
  
• due to Wallerian degeneration; not drawn (source: Boards and Wards, 3rd Edition)
• occurs since ATP is needed for myelin production and ATP isn't being made to the same quantity
  
• Neuropathy may manifest as foot drop or wrist drop much like lead poisoning does in adults
  
• Wernicke's encephalopathy is reversible (We-versible Wernicke's)

________

Say the above patient was given glucose without correcting his thiamine deficiency, it would precipitate...

Korsakoff's Amneisa

These are the Mammillary Bodies:

These are the mammillary bodies on drugs:

Any questions?
(source: The Medical Journal of Australia )

• anterograde and retrograde amnesia
  
• Bilateral hemorrhagic necrosis of mammillary bodies
  
• mammillary bodies are in the hypothalamus and are part of the limbic system
  
• irreversible
  

Treatment: IV Thiamine and THEN glucose

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

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!

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