Vitamin A, Zinc, Selenium

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Vitamin A in general

Vitamin A is a fat-soluble vitamin, as are D, E, and K. (All Dogs Eat Kittens).

Three main physiologic roles of vitamin A that you need to know for the Step1:

1) Is converted from 11-cis-retinal to 11-trans-retinal in phototransduction. Any vignette that mentions nyctalopia (night blindness) in relation to nutrition = vitamin A deficiency.

2) Supports proper immune functioning (i.e., deficiency ↑ infections)

3) Enables differentiation of tissues (i.e., prevents skin cancer via inhibiting squamous metaplasia).

Vitamin A as a treatment

The USMLE is also obsessed with the fact that all-trans-retinoic acid (a vitamin A derivative) can treat acute promyelocytic leukemia (AML subtype M3). This is because vitamin A induces differentiation of leukemic cells into mature neutrophils.

In the past, there have been studies demonstrating the effectiveness of vitamin A in treating measles. USMLE Step1 likes this. God knows why. Therefore, vitamin A deficiency = ↑ susceptibility to measles. Know that.

The sequence of treatment for acne is generally as follows (yes, you need to know this; this is not pedantic; acne is one of the most common conditions in the population):

Topical retinoids (e.g., tretinoin gel) → topical benzoyl peroxide → topical clindamycin → oral tetracycline → oral isotretinoin

If you talk to a dermatologist, he or she will tell you there are different types of acne and regimens can sometimes differ. But the above sequence is for most patients. Particularly knowing topical retinoids are first, followed by benzoyl peroxide, is HY.

Isotretinoin, used to Tx severe acne, is oral high-dose vitamin A that is teratogenic. Before you administer this drug to a female of child-bearing age, perform a β-hCG.

If the USMLE asks you how vitamin A (retinoids) works for acne, the answer is:

1) It is a transcription factor.

2) It shuts off sebum production.

Both are bolded because of their high-yieldness.

Tangentially, benzoyl peroxide opens poors and kills bacteria.

Vitamin A deficiency

Vitamin A deficiency and excess have been known to cause xerosis cutis, aka DRY SKIN.

Bitot spots (grey plaques on conjunctiva) and corneal metaplasia/necrosis can be seen in severe vitamin A deficiency.

As mentioned above, vitamin A deficiency can increase risk of cancer, notably squamous cell carcinoma, as well as theoretically increase the risk of measles in a population.

Hypervitaminosis A (toxicity)

The two most common causes of vitamin A toxicity tested on Step1 are isotretinoin and consumption of ursine (bear) liver. Liver has the highest concentration of vitamin A compared to any other food.

The most commonly tested consequences of vitamin A toxicity are increased intracranial pressure (pseudotumor cerebri).

Be on the lookout for papilledema and cerebral edema.

Hypervitaminosis A, obesity, danazol, and OCPs are notable Step1-tested causes of pseudotumor cerebri.

Whereas the other fat-soluble vitamins are stored in adipocytes systemically, vitamin A is notably concentrated in the liver in hepatic stellate cells (aka Ito cells). These cells are found in the perisinusoidal space (space of Disse) and differentiate into myofibroblasts, which produce collagen, during hepatic fibrosis/cirrhosis.

Excess vitamin A is also teratogenic.

If they ever ask you what vitamin A teratogenicity results in: Answer = cleft lip/palate.

If they ever ask you about why vitamin A is a teratogen: Answer = disrupts homeobox gene.

Now I’m going to briefly mention selenium and zinc.

How do they relate to vitamin A? They don’t whatsoever. It’s just that they HY points are short so I decided to not make a separate post for them.

Selenium

All you need to know about selenium for Step1 is that it’s a cofactor for glutathione peroxidase. That’s it. And in case you don’t recall, glutathione peroxidase converts H2O2 + reduced glutathione (–SH) → H2O + oxidized glutathione (-S–S-).

This ultimately ties into G6PD deficiency because of how the reaction works together with glutathione reductase, which requires NADPH.

The hydrogen peroxide from this reaction is made in the respiratory burst:

Zinc

Roughly 80% of questions that ask about zinc deficiency on USMLE Step1 will present a patient with anosmia (↓ ability to smell) and dysgeusia (↓ ability to taste). These patients also have ↓ wound healing.

About 20% of the time you’ll get a question on zinc deficiency that gives a patient with acrodermatitis enteropathica, an autosomal recessive condition characterized by ↓ zinc absorption, dermatitis of orifices/limbs, diarrhea, and alopecia.

Zinc deficiency has also been known to cause infertility.

Just as fructose is secreted into semen by the seminal vesicles, the prostate secretes zinc into semen, which helps stabilize DNA-containing chromatin in spermatazoa.

1. What does vitamin A do in phototransduction?

 
 

2. Which of the following is vitamin A used for physiologically? (Select all that apply)

 
 
 

3. What type of leukemia can vitamin A (all-trans retinoic acid) help treat?

4. What is the translocation associated with acute promyelocytic leukemia (APL; aka AML M3)?

 
 
 
 
 
 
 

5. Vitamin A deficiency increases the risk of which of the following? (one answer; worth 3 points)

 
 
 
 
 
 
 
 

6. Vitamin A causes the differentiation of promyelocytes in APL into what?

7. What is the general sequence for acne treatment in most patients?

8. What is imperative to consider in a patient starting isotretinoin?

9. Which of the following is/are true regarding vitamin A? (Select all that apply)

 
 
 

10. What are Bitot spots?

11. What is pseudotumor cerebri? And what are four causes?

12. What are two notable causes of vitamin A toxicity?

13. a) In terms of teratogenicity, what does vitamin A most frequently cause?

b) And if the USMLE asks you for which gene is disrupted, what’s the answer?

14. Vitamin A is stored where in the liver?

15. Selenium is notably a cofactor for what enzyme?

16. What is acrodermatitis enteropathica?

17. Which of the following are notably seen in zinc deficiency? (Select all that apply)

 
 
 
 
 

18. What secretes zinc into semen?