Official Step 1 High Yield Concepts Thread

[Transposony]

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Let's discuss our doubts/offer clarifications about mechanisms/concepts for Step 1

ASK ANY QUESTIONS here.

To kick start the thread here is something I didn't know:

1. Penicillin-binding proteins (PBPs) are actually enzymes (transpeptidases & carboxypeptidases) which cross-link peptidoglycan. Penicillins binds to these enzymes and inactivating them thereby preventing cross-linkiing of peptidoglycan.

2. Periplasmic space (Gram -ve) contain proteins which functions in cellular processes (transport, degradation, and motility). One of the enzyme is β-lactamase which degrades penicillins before they get into the cell cytoplasm.
It is also the place where toxins harmful to bacteria e.g. antibiotics are processed, before being pumped out of cells by efflux transporters (mechanism of resistance).

There are three excellent threads which you may find useful:

List of Stereotypes

Complicated Concepts Thread

USMLE images

 

[Transposony]

Which organ in the body makes protease inhibitor ?

 

[seminoma]

Which organ in the body makes protease inhibitor ?

Liver...? Is this a trick question 🙁?

A1AT right?

 

[seminoma]

By what process does a normal VHL protein product contribute to downregulation/inhibition of HIF-1?

 

[Transposony]

Liver...? Is this a trick question 🙁?

A1AT right?

Not really HY. Just minutiae.

Autodigestion of the pancreas is prevented by the packaging of pancreatic proteases in precursor form and by the synthesis of protease inhibitor i.e., pancreatic secretory trypsin inhibitor (PSTI) which can bind and inactivate trypsin.

 

[Transposony]

I don't know, but I'm going to guess. Illeal damage and scarring from Crohn's means you can't absorb bile salts. Decreased levels of bile salts due to loss via lack of enterohepatic recirculation leads to cholesterol stones.

That paragraph is the sum of like 5 minutes of intense thinking. My head hurts now. I hope you're proud of yourself.

This is an errata in FA.
Pigment stones due to increased amounts of bile salts reaching the cecum and solubilizing unconjugated bilirubin, allowing their reabsorbtion with subsequent hyperbilirubinobilia.

 

[stepone2015]

This is an errata in FA.
Pigment stones due to increased amounts of bile salts reaching the cecum and solubilizing unconjugated bilirubin, allowing their reabsorbtion with subsequent hyperbilirubinobilia.

Can you explain that more? I'm not following where the unconjugated bilirubin is coming from or going to...

 

[aspiringmd1015]

By what process does a normal VHL protein product contribute to downregulation/inhibition of HIF-1?

this was straight out of robbins, ubiquitin/proteasome mechanism slicing up hif 1 like string cheese

 

[aspiringmd1015]

I remember pholston writing something up about the mechanism of magensium on PTH secretion, i wrote it down, and i wrote it down so fast i cant read a word of what i said lol can anyone explain it again(how moderate mg def causes increased pth release, and severe mg def causes decreased pth release)

 

[aspiringmd1015]

also, wiki mentions tertiary adrenal insuff is associated with tumors and trauma etc. FA mentions loss f the HPA axis due to treatment, sooo?

 

[Transposony]

Can you explain that more? I'm not following where the unconjugated bilirubin is coming from or going to...

Sure.
Normally, CB is secreted into the intestine as bile. In the intestine, CB cannot be absorbed due to large size and polarity unless intestinal enzymes cause deconjugation of CB to UB. This UB is rapidly converted to urobilinogen by bacterial reduction followed by urobilin, stercobilin etc. Some of this urobilinogen is absorbed and excreted into urine.
Normally, bile salts are primarily absorbed in the terminal ileum (95%) by active transport.
However, in terminal ileal disease these bile salts are not absorbed and therefore solubilize UB in the colon thereby preventing the bacterial reduction to urobilinogen.

 

[seminoma]

also, wiki mentions tertiary adrenal insuff is associated with tumors and trauma etc. FA mentions loss f the HPA axis due to treatment, sooo?

In regard to what?

Tertiary just means in the hypothalamus. Secondary would be the pituitary (ACTH) and primary is in the adrenal itself.

 

[stepone2015]

Sure.
Normally, CB is secreted into the intestine as bile. In the intestine, CB cannot be absorbed due to large size and polarity unless intestinal enzymes cause deconjugation of CB to UB. This UB is rapidly converted to urobilinogen by bacterial reduction followed by urobilin, stercobilin etc. Some of this urobilinogen is absorbed and excreted into urine.
Normally, bile salts are primarily absorbed in the terminal ileum (95%) by active transport.
However, in terminal ileal disease these bile salts are not absorbed and therefore solubilize UB in the colon thereby preventing the bacterial reduction to urobilinogen.

I'm sorry, but maybe I'm having a 'foggy brain day' or something. If the bile salts aren't absorbed, that means you're going to be losing the bile into the feces. How would that result in pigment stones? Where is this excess billirubin coming from? I just checked Wiki, and it also says cholesterol stones, not pigment stones.

 

[Transposony]

What causes black liver in Dubin-Johnson syndrome ?

 

[dfib slim]

What causes black liver in Dubin-Johnson syndrome ?

Epinephrine metabolites in lysosomes.

 

[dfib slim]

Which antibiotic can be given for bacterial endocarditis in an IV drug user but is ineffective in pneumonia caused by the same organism, and why?

 

[Transposony]

Which antibiotic can be given for bacterial endocarditis in an IV drug user but is ineffective in pneumonia caused by the same organism, and why?

Daptomycin.
Staph aureus.
Binds surfactant.

 

[aspiringmd1015]

In regard to what?

Tertiary just means in the hypothalamus. Secondary would be the pituitary (ACTH) and primary is in the adrenal itself.

as in, if im giving exogenous steroids, its acting on the hypothalamus to decrease CRH?

 

[faisal 2000]

how does vit A intoxication cause carotenemia ?

 

[Radiolucent]

how does vit A intoxication cause carotenemia ?

Carotenoids (vitamin A among others) also function as a yellow-orange pigment. Excessive intake of carotenoids colours the skin yellow-orange.

 

[Radiolucent]

A patient with Hodgkins lymphoma comes to your clinic with a rash 6 weeks after starting chemo.
Your examination of the patient reveals a linear rash appearing mainly over his left scapula, shown on the picture below.

Diagnosis?

 

[stepone2015]

A patient with Hodgkins lymphoma comes to your clinic with a rash 6 weeks after starting chemo.
Your examination of the patient reveals a linear rash appearing mainly over his left scapula, shown on the picture below.

Diagnosis?

Chemo induced rash, maybe busulfan?

 

[Radiolucent]

Very good. This flaggelate type pigmentation is a typical Bleomycin side effect (FA only says rash) but can be seen in other conditions as well.

 

[Transposony]

how does vit A intoxication cause carotenemia ?

Vit A intoxication and carotenemia are two different things.
There cannot be Vit A intoxication due to carotenemia as beta-carotene's rate of conversion to vit A is not high enough to cause vit A toxicity.

 

[Radiolucent]

Vit A intoxication and carotenemia are two different things.
There cannot be Vit A intoxication due to carotenemia as beta-carotene's rate of conversion to vit A is not high enough to cause vit A toxicity.

Wait, Im getting confused.
I thought that carotenemia was the orange-yellow discoloration of the skin by carotenoids and that Vit A is a carotenoid? So the latter part is wrong?

 

[seminoma]

DIT says testosterone can be used to treat ER+ breast cancer..? How does that work?

I guess T would inhibit the HPG axis, but wouldn't the exogenous T just be converted to estrogen via aromatase?

 

[Transposony]

Wait, Im getting confused.
I thought that carotenemia was the orange-yellow discoloration of the skin by carotenoids and that Vit A is a carotenoid? So the latter part is wrong?

Vitamin A is a terpene.
β-Carotene is composed of two retinyl groups, and is broken down in the mucosa of the small intestine by β-carotene 15,15'-monooxygenase to retinal, a form of vitamin A. β-Carotene can be stored in the liver and body fat and converted to retinal as needed, thus making it a form of vitamin A.

 

[aspiringmd1015]

DIT says testosterone can be used to treat ER+ breast cancer..? How does that work?

I guess T would inhibit the HPG axis, but wouldn't the exogenous T just be converted to estrogen via aromatase?

doesnt testo increase sex hormone binding globulin? binding up estrogen?

 

[aspiringmd1015]

could cinacalcet be given to Rx familial hypocalcuric hypocalcemia?

 

[aspiringmd1015]

also the aplastic anemia and agranulocytosis effect of PTU due to its hapten response? thio=sulphur= binds to proteins= hapten response on blood cells?

 

[stepone2015]

also the aplastic anemia and agranulocytosis effect of PTU due to its hapten response? thio=sulphur= binds to proteins= hapten response on blood cells?

What you're describing sounds more like a hemolytic anemia. The PTU effect would be more direct destruction of marrow cells without immune involvement. For example, benzene causes AA by intercalating into DNA. Radiation is also a cause of AA.

 

[aspiringmd1015]

it could be aplastic if the hapten response occured in the bone marrow, no?

 

[seminoma]

doesnt testo increase sex hormone binding globulin? binding up estrogen?

Androgens do inhibit SHBG synthesis, but SHBG binds with greater affinity for test than estradiol.. so inhibiting SHBG synthesis doesn't seem likely to decrease free estradiol levels.

 

[aspiringmd1015]

yeah sorry, thought testosterone increased SHBG.

 

[aspiringmd1015]

with congenital hypothyroidism related to iodine deficiency, is it iodine defiency in the mother? or in the neonate which causes the cretinism

 

[stepone2015]

with congenital hypothyroidism related to iodine deficiency, is it iodine defiency in the mother? or in the neonate which causes the cretinism

Maternal if before ~20 weeks gestation (fetal thyroid opens shop around then). If after 20 weeks, the fetus is big enough to require its own production, but if the mom is getting enough iodine, then the baby should be fine. There's a dyshormonogenic goiter which is when the fetus can't make thyroid hormone due to a defect in, I think, thyroid peroxidase.

 

[MrNeuro]

Androgens do inhibit SHBG synthesis, but SHBG binds with greater affinity for test than estradiol.. so inhibiting SHBG synthesis doesn't seem likely to decrease free estradiol levels.

http://breast-cancer-research.com/content/11/5/212

"Clinical observations and experimental data indicate that androgens inhibit mammary growth, and they have been used in the past with success to treat breast cancer"

pts w/ klinefelters also have increased risk of brst cancer

i couldn't find a link but I think I read something that said test is no longer used in ER bc of aromatase activity however it has been shown that test + arom. inhibitors in non brst cancer pts decreased their risk......take this w/ a grain of salt

Figure 2 in that paper is also pretty interesting....

 

[seminoma]

http://breast-cancer-research.com/content/11/5/212

"Clinical observations and experimental data indicate that androgens inhibit mammary growth, and they have been used in the past with success to treat breast cancer"

pts w/ klinefelters also have increased risk of brst cancer

i couldn't find a link but I think I read something that said test is no longer used in ER bc of aromatase activity however it has been shown that test + arom. inhibitors in non brst cancer pts decreased their risk......take this w/ a grain of salt

Figure 2 in that paper is also pretty interesting....

Haven't seen you since MCAT. Hows step studying going?

 

[Kingella]

What causes black liver in Dubin-Johnson syndrome ?

catecholamine breakdown products

 

[scoKraz4]

I remember pholston writing something up about the mechanism of magensium on PTH secretion, i wrote it down, and i wrote it down so fast i cant read a word of what i said lol can anyone explain it again(how moderate mg def causes increased pth release, and severe mg def causes decreased pth release)

http://www.ncbi.nlm.nih.gov/pubmed/12105390

 

[pathologyDO]

Alright, who can tell me the major effects that normal alcohol metabolism leading to increased NADH:NAD+ ratio has ? (emphasis on glycolysis)

 

[aspiringmd1015]

increased lactate, incrreased glycerol 3 phosphate(hepatosteatosis), and malate so no gluconeo(hypoglycemia), hope they arent taking propanolol!

 

[pathologyDO]

Increased NADH:NAD+ causes:

1. Increased lactate (Pyruvate + NADH -> Lactate + NAD+)

2. OAA is decreased in order to generate NAD+ (OAA + Malate -> NAD+) -> this decreases TCA

3. Isocitrate Dehydrogenase is inhibited by NADH -> this also decreases TCA

4. Decreased TCA -> accumulation of acetyl-CoA -> ketogenesis -> ketoacidosis

5. Pyruvate & OAA depletion -> inhibition gluconeogenesis, stimulation FA synthesis -> fasting hypoglycemia

 

[aspiringmd1015]

anyone know the mechanism of hypohidrosis and other findings in fabry's disease? does the accumlated ceramide do something in particular?

 

[Transposony]

DIT says testosterone can be used to treat ER+ breast cancer..? How does that work?

I guess T would inhibit the HPG axis, but wouldn't the exogenous T just be converted to estrogen via aromatase?

It's fourth line therapy for breast cancer (along with progestogens & estrogens--yes, I am not kidding!) when nothing else has worked and no one really knows how it works.
Not HY for even Breast fellows.
Extremely low yield for Step 1 , not sure why DIT even mentions it.

 

[seminoma]

How would an ER+ breast cancer stain look? Would the stain be positive in both the nucleus and the cytoplasm? Or only the cytoplasm? Or only the nucleus?

I don't know the answer, but I'm hoping someone does.

We know that the ER is located in the cytoplasm and only translocates to the nucleus upon binding to Estrogen. But how does the stain work? Does the stain bind to both ER-E complexes? Only to ER? Does the stain itself bind the E-binding site and therefore cause ER translocation to the nucleus? Does the stain bind to a non-E binding site and therefore stain cytoplasmic ER?

 

[stepone2015]

How would an ER+ breast cancer stain look? Would the stain be positive in both the nucleus and the cytoplasm? Or only the cytoplasm? Or only the nucleus?

I don't know the answer, but I'm hoping someone does.

We know that the ER is located in the cytoplasm and only translocates to the nucleus upon binding to Estrogen. But how does the stain work? Does the stain bind to both ER-E complexes? Only to ER? Does the stain itself bind the E-binding site and therefore cause ER translocation to the nucleus? Does the stain bind to a non-E binding site and therefore stain cytoplasmic ER?

There's going to be some bound and in the nucleus at anyone one time. Found a picture of PR+ cancer: http://biocare.net/wp-content/uploads/302.jpg

 

[stepone2015]

8 year old recent European immigrant is brought to the emergency room and pronounced dead shortly after. He had collapsed in the middle of his classroom. He had no significant past medical history according to his mother except for a cochlear implant placed shortly after birth. He had not been feeling sick prior to collapsing.

Cause of death?

 

[aspiringmd1015]

regarding electrolyte abrnormalities, is the section in Renal FA enough? or should we know more about it?

 

[Radiolucent]

8 year old recent European immigrant is brought to the emergency room and pronounced dead shortly after. He had collapsed in the middle of his classroom. He had no significant past medical history according to his mother except for a cochlear implant placed shortly after birth. He had not been feeling sick prior to collapsing.

Cause of death?

Of course impossible to say based on that information.
Ill bite though and guess either something like Lange-Jervell-Nielsen syndrome or something to do with a congenital infection/lack of immunization (secondary to rubella?).

Close?

 

[seminoma]

regarding electrolyte abrnormalities, is the section in Renal FA enough? or should we know more about it?

I think FA covers the important diseases, but the underlying physiology is not explained well. If you understand the lytes stuff in FA I think you're solid (e.g. why is NH3 synthesis decreased in Type 4 RTA or why does type 2 RTA initially have urine pH >5.5). If you just have it memorized I might be worried.

Edit: Although I guess that's true for most things in FA>