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Welcome to didelphusโ€™s page.
Contributor score: 70


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 +2  visit this page (nbme21#5)
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A PDA essentially creates a high-flow heart failure situation in the baby. Since a fraction of the LV output is returned without reaching the body, in order to maintain a normal CO to the body the left ventricle must pump a higher volume. This would also cause higher than normal pulmonary capillary flow.

I think some of the other question are getting at the idea that we don't know the direction of flow for sure. If the flow was aorta-->lungs, the systemic PO2 would be normal and RV PO2 high. But if it's opposite, the opposite would be true.

Since PDAs are maintained by PGE2, that would contribute to a low peripheral vascular resistance.

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didelphus  *another user noted that this wouldn't impact RV oxygen because the blood is added to the pulmonary artery, which has exited the RV. +3

 +1  visit this page (nbme21#35)
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Any idea why hyperchloremia isn't an answer? The diarrhea would cause an normal anion gap (hyperchloremic) metabolic acidosis.

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charcot_bouchard  this is the problem bet uw and nbme. in uw it would be for sure a gotcha ques. but in nbme they are usually looking for most obvious. also look what they are asking "most likely". baby would dev low Na before acidosis. Thats my 2 cents +29
temmy  hyperchloremia will not account for the seizure that brought the patient to the hospital. seizures according to first aid is caused by hypocalcemia and hyponatremia +1
cry2mucheveryday  Children with diarrhoea who drink large amounts of water or other hypotonic fluids containing very low concentrations of salt and other solutes, or who receive intravenous infusions of 50% glucose in water, may develop hyponatraemia. This occurs because water is absorbed from the gut while the loss of salt (NaCl) continues, causing net losses of sodium in excess of water. The principal features of hyponatraemic dehydration are: there is a deficit of water and sodium, but the deficit of sodium is greater; serum sodium concentration is low (<130 mmol/l); serum osmolality is low (<275 mOsmol/l); the child is lethargic; infrequently, there are seizures. https://rehydrate.org/diarrhoea/tmsdd/2med.htm#CONSEQUENCES%20OF%20WATERY%20DIARRHOEA +
cry2mucheveryday  Also, why is this being given formula...? May be lactase deficiency...which leads to osmotic diarrhea...leads to hyponatremia(goljan) Aren't newborns supposed to be kept on exclusive breast milk till 6 months?? +
hello  @cry2mucheveryday Don't read too much into it. The fact that the baby is receiving formula isn't relevant to answering the Q. Btw, not everyone breast feeds. Additionally, the Q wouldn't make much sense if it said "they ran out of breastmilk"... +1
hello  @cry2mucheveryday Being on formula then the parents running out of formula is more of a clue for water intoxication. This is typically the scenario that water intoxication presents. However, I suppose if for some reason the baby was being breastfed and the parents switched to exclusively waterfeeding (and no other foods), then water intoxication would also result. +




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submitted by hayayah(1212), visit this page
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Although half these hormones can actually also be secreted from the duodenum, the duodenum is associated the most with CCK release.

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didelphus  Gastrin, intrinsic factor, and pepsin are secreted by the stomach. VIP is synthesized in neurons, so CCK (from I cells of duodenum) would be most directly affected by a duodenectomy. +25
teepot123  fa 19 pg 365 +


submitted by calcium196(12), visit this page
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Ubiquitin-mediated proteolysis is not reversibly affected by insulin. The question asks for reversible ways that insulin affects it, and ubiquitination would lead to degradation via proteases, which is not reversible. Nuclear/cytoplasmic shunting makes sense because FOXO is a transcription factor, so it canโ€™t do its job if it is in the cytoplasm!

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meningitis  Thank you for your explanation! One question: How about the serine phosphorylation? Is it answered by pure memorization that the FOXO TF is serine phosphorylated, or is it a general fact that all TF's are serine-threonine phosphorylated? +
tsl19  I'm not sure, but it may be as simple as this: ubiquitin-mediated proteolysis is irreversible, but both N/C shuttling and phosphorylation are generally reversible processes. +
didelphus  I also guessed that FOXO must be a part of the PI3K pathway, since insulin regulates metabolism through PI3K and the question stem specifically mentions that. Phosphorylation is a major part of that pathway, so even indirectly phosphorylation would regulate FOXO. Frustrating question. +21
niboonsh  yes, FOXO is affected downstream of the activation of PI3K. This is a really good video that explains the whole cascade https://www.youtube.com/watch?v=ewgLd9N3s-4 +2
alexb  According to wikipedia (https://en.wikipedia.org/wiki/FOXO1) phosphorylation of FOXO1 is irreversible. This is referring to phosphorylation of serine residues on FOXO by Akt, which occurs in response to insulin. But the NBME answer suggests it's reversible. What's up? +2
almondbreeze  could wiki be wrong on phosphorylation being irreversible? according to this article, it is a reversible process: regulation of FoxO transcription factors by reversible phosphorylation and acetylation (https://www.sciencedirect.com/science/article/pii/S0167488911000735#s0010) some wiki info, however, is helpful : In its un-phosphorylated state, FOXO1 is localized to the nucleus, where it binds to the insulin response sequence located in the promoter for glucose 6-phosphatase and increases its rate of transcription. FOXO1, through increasing transcription of glucose-6-phosphatase, indirectly increases the rate of hepatic glucose production.[19] However, when FOXO1 is phosphorylated by Akt on Thr-24, Ser-256, and Ser-319, it is excluded from the nucleus, where it is then ubiquitinated and degraded. The phosphorylation of FOXO1 by Akt subsequently decreases the hepatic glucose production through a decrease in transcription of glucose 6-phosphatase. +
leaf_house  It seems like the phosphorylation from Akt leads to destruction, but maybe the assumption is that that phosphorylation step (excluding every other step of ubiquitin-proteosome pathway) is reversible, where proteolysis is final. @niboonsh video is good but doesn't split this one. +


submitted by masonkingcobra(408), visit this page
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Link

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necrotizingfasciitis  Going off of the comments people have posted above & kinda bringing things together: PDA flows from aorta to pulmonary arteries, which reverses after birth. This means de-oxygenated blood flow from the pulmonary arteries to the aorta & less volume being sent to the LF side of the heart. This results in a decreased afterload because there is less blood flowing from the lungs to re-fill the LF ventricle, & the heart is still pumping with the same force as before, so the same volume of blood is leaving, but less in entering the LF side of the heart. From here, you use CO = SV x HR SV = preload - afterload (which is decreased due to the PDA) This results in SV being larger than normal, so when you plug that into CO = SV x HR you get a higher number for cardiac output. +
didelphus  The ductus arteriosus flows from PA --> aorta in utero to bypass the lungs, which have extremely high resistance to flow. This reverses after birth due to a drop in PGE2 (which was supplied by the placenta) and increase in left-sided systemic resistance. So a PDA typically flows aorta --> PA (assuming there are no other defects). +


submitted by didelphus(70), visit this page
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A PDA essentially creates a high-flow heart failure situation in the baby. Since a fraction of the LV output is returned without reaching the body, in order to maintain a normal CO to the body the left ventricle must pump a higher volume. This would also cause higher than normal pulmonary capillary flow.

I think some of the other question are getting at the idea that we don't know the direction of flow for sure. If the flow was aorta-->lungs, the systemic PO2 would be normal and RV PO2 high. But if it's opposite, the opposite would be true.

Since PDAs are maintained by PGE2, that would contribute to a low peripheral vascular resistance.

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didelphus  *another user noted that this wouldn't impact RV oxygen because the blood is added to the pulmonary artery, which has exited the RV. +3


submitted by hayayah(1212), visit this page
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With this question, I think they want you to recognize that the patient isn't having chest pain related to the heart. They emphasize several rib fractures and a pneumothorax but don't indicate any heart damage (lack of adventitious sounds = no pulmonary edema indicated or a lung issue related to heart problem).

The pericarditis is what's innervated by the phrenic n. Seeing as how his heart is fine, the fractured ribs are probably what are causing him pain via the intercostal nerves.

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didelphus  Visceral pain is typically poorly localized (heart attacks are usually described as "crushing pressure" that radiates to the shoulder or neck), so this patients "sharp" right-sided pain in the setting in multiple right-sided rib fractures is likely related to the ribs. The intercostals run with the ribs and provide sensation to the chest wall. +18


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