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NBME 22 Answers

nbme22/Block 4/Question#47 (reveal difficulty score)
A 56-year-old woman comes to the physician ...
Maintenance of basement membrane integrity 🔍 / 📺 / 🌳 / 📖
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 +14  upvote downvote
submitted by bubbles(79)
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Basement membrane integrity is the determinant of full lung recovery following pulmonary insult.

Summary:

(1) loss of basement membrane integrity is critical in determining the “point of no return,” and contributes to the inability to reestablish normal lung architecture with promotion of fibrosis;

(2) loss of epithelial cells, endothelial cells, and basement membrane integrity in usual interstitial pneumonia associated with idiopathic pulmonary fibrosis leads to destroyed lung architecture and perpetual fibrosis;

(3) transforming growth factor-β is necessary, but not entirely sufficient, to promote permanent fibrosis;

(4) persistent injury/antigen/irritant is critical for the propagation of fibrosis;

(5) idiopathic pulmonary fibrosis is an example of a process related to the persistence of an “antigen(s),” chronic inflammation, and fibrosis; and

(6) unique cells are critical cellular players in the regulation of fibrosis.

citation: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645241/

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kernicterusthefrog  Lovely +
endochondral1  any FA or pathoma or uworld correlation? +
endochondral1  or was this a random? +
taediggity  Type II pneumocytes serve as the stem cell precursors, w/out those you're more or less fucked: FA 2020 pg 661 +4

Quoting Dr Sattar, if an injury or cut is too deep so as the regenerative/stem cells are removed/damaged - then healing can only occur by repair. Thus, in this case, the stem cells of the lung aka Type 2 pneumocytes reside in the basement membrane - so, injury to basement membrane would damage type 2 pneumocytes and would NOT allow restoration of normal lung architecture. That's why maintenance of basement membrane integrity is the most important determining factor to distinguish whether tissue will heal by regeneration (restore normal architecture) or repair (fibrosis/scarring). Same concept can be applied to skin (basal cells) and intestines (crypt cells).



 +11  upvote downvote
submitted by drdoom(1206)
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You have to think about it this way: the basement membrane is the “scaffolding” on which [restorative] healing occurs. So, yes, stem cells (type II pneumocytes) would be involved in that healing process but they couldn’t restore the normal architecture (“no abnormalities”) without the ‘skeleton’ of the basement membrane telling them where to go, in what direction to grow, which way is “up”, etc. If the basement membrane is destroyed, you can still get healing, but it won’t be organized healing -- it’ll be disorganized healing, which does not appear as normal tissue. (Disorganized healing is better than no healing, but without a BM, the regenerating cells don’t have any “direction” and therefore can’t restore the normal architecture.)

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drdoom  by "restorative" i mean healing which restores the previous (and normal) tissue architecture. for that to happen, you need an intact basement membrane! +2
nwinkelmann  Yes, this a great summary to the post by @bubbles and the article he posted! Another way to think of the question is not, what causes repair, but what causes irreversible injury/fibrosis. That article explained an experiment that showed TGF-beta was necessary to initiate fibrosis, but if BM was intact and TGF-beta was removed, the fibrosis didn't persist, i.e. intact BM is protective against TGF-beta. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645241/ +1



 +1  upvote downvote
submitted by shaydawn88(8)
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I would think resolution involves the stem cells (type II pneumocytes). Is the intact basement membrane the answer because it limits spread?

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aesalmon  I would also like to know if anyone can answer this question - I saw it as a Sattar "one day, one week, one month" kind of question. Its probably very simple but I still don't get it +
bubbles  I posted a new comment explaining: basement membrane integrity is the strongest determinant of full fx recovery following pulmonary insult :) +5
drdoom  You have to think about it this way: the basement membrane is the “scaffolding” on which [restorative] healing occurs. So, yes, stem cells (type II pneumocytes) would be involved in that healing process but they couldn’t restore the *normal* architecture (“no abnormalities”) without the ‘skeleton’ of the basement membrane telling them where to go, in what direction to grow, which way is “up”, etc. If the basement membrane is destroyed, you can still get healing, but it won’t be organized healing -- it’ll be *disorganized* healing, which does not appear as normal tissue. (Disorganized healing is better than no healing, but without a BM, the regenerating cells don’t have any “direction” and therefore can’t restore the normal architecture.) +9
nwinkelmann  Yes, this a great summary to the post by @bubbles and the article he posted! Another way to think of the question is not, what causes repair, but what causes irreversible injury/fibrosis. That article explained an experiment that showed TGF-beta was necessary to initiate fibrosis, but if BM was intact and TGF-beta was removed, the fibrosis didn't persist, i.e. intact BM is protective against TGF-beta. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645241/ +



 +1  upvote downvote
submitted by ls3076(92)
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can anyone explain why (D) metaplasia is incorrect?

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angelaq11  because metaplasia would be a transformation of the normal architecture of the respiratory epithelium to one that does not belong there, in response to chronic irritation. This woman had pneumococcal pneumonia that was correctly (and I dare say promptly) treated, so she suffered an acute rather than a chronic insult. +
blueberrymuffinbabey  because metaplasia isn't how the normal healing/regeneration response happens in the alveoli. the type 2 pneumocytes serve as stem cells/precursors to both type 1 and 2 pneumocytes so the regeneration is not metaplasia. +1



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