I had one question about the practice questions for the nephritic syndrome lecture. Question 2 has us matching the pictures with the buzzwords. Buzzword 8 is MRSA and you have it matched to image A in the key, which correlated with PSGN. My understanding is that MRSA is a staphylococcal infection (S. Aureus), not streptococcal. As you mentioned in the lecture, that would make it correlated with nonstreptococcal GN, and therefore 8 would not correlate with any of the images attached.

I noticed that on question 2 #9 that the answer key says TBMN is Autosomal Recessive but that in the PP it says Autosomal Dominant? May I please get some clarification?

Thank You!

Hi Dr. Ensign,

I had a question about slide 15 on FSGS. The slide says that diabetes is the most common cause of primary nephrotic syndrome in adults.

It was unclear to me if you meant that it was the most common cause of primary nephrotic syndrome generally, or that it was the most common cause of FSGS?

I apologize if this is a basic question, but I'm wasn't sure if diabetic nephrotic syndrome was separate pathological process or if it would qualify as an adaptive secondary cause of FSGS.

Thank you!

I have a question about the Pathogenesis of Glom Inj lecture. With regard to Pattern 3, Nephritic Syndrome, I understand that RBCs are bigger than protein and that with this pattern there is enough damage to the glomerulus that both hematuria and proteinuria occur. Given that, I don't understand how hematuria could occur without proteinuria in other diseases. If there is enough damage for blood to filter through the glom when it isn't supposed to, how would protein, which is smaller, not escape too?

Thanks!

I had a question about the Clues slide at the end of the nephritic lecture. It says in the clues page that FSGS can have both IgG and IgM involvement, but in the explanation for question 3 in the nephrotic questions it says that the only disease we have covered so far with IgG involvement is membranous glomerulonephropathy. Can you clarify if FSGS is both IgG and IgM, or just IgM? Thank you in advance!

I am a little confused about RPGN and GFR. On your slide #5 you mentioned it results in increasing eGFR over a short period of time however, on your lecture recording you said the GFR goes down and serum creatinine goes up. Would you be able to clarify if the GFR does up or down with RPGN? Thank you!

Do the autoantibodies attach to free-floating antigens in the system and then form a complex that attaches to the PLA2 receptor? Or are the antigens already on the receptor and the autoantibodies attach to the antigen there?

My question is similar with secondary planted. Are the antigens already in the subepithelial layer before attaching to an antibody? And are they attaching to something specific in the subepithelial area?

Slide 22 of nephrotic syndrome

I am not sure if this is just me or if there is an issue with recordings, but there seems to be a slight delay in the audio versus your drawings for any of the histology drawings. It has been difficult to follow along with your drawings as you are identifying structures.

If possible, could you upload a packet or practice document for us to identify the histology slides?

Format:

Slide A: Blank histology/EM photo with you asking us to identify structures.

Slide B: Answers slide of said structures, and then ask us to clinically correlate.

Slide C: Answer slide for slide B at the very end of the document.

Hello Dr. Ensign,

Could you please help me visualize the "gbm splitting" in MPGN type 1 on electron microscopy? I am not entirely sure how to tell from the slide. I attached it here. Thank you!

I seem to always get lost in the weeds when it comes to determining if something is a symptom, a sign, a syndrome, or a disease, or even something that is a disease secondary to disease. May you have any advice  please on how I can better sort this out?  I thought about this more after seeing the clues slide for the different clinical syndromes. Thank you 

In the case of nephritic syndromes, why is it that the basement membrane is destroyed enough or potentially widened enough to allow red blood cells to go through, but GFR is decreased? My initial thought is that if there are holes big enough for red blood cells to go through. Then GFR would increase because more fluid would be able to leak out through those same holes. My other thought is if the proteins and red blood cells are leaking through the glom, maybe that decreases overall capillary oncotic pressure, causing Edema in the rest of the body, which would then potentially decrease GFR. Thanks!

Do you have any helpful pointers in distinguishing between Lupus (subtype IV) wire loop lesions & frank capillary thickening (ie membranoproliferative)? Or do we just need to use outside clues to distinguish between the two?

Hello Dr. Ensign,

I am working through the practice questions relating to the lecture "Overview of Glomerular Diseases" and I am a little confused on the matching with question 2. 

I can tell that A is a normal glomerulus. Since Alport Syndrome in the beginning shows no changes in light microscopy, we can assume that A could be early stages of Alport Syndrome? 

Is 7 also A because it is relating to Alport Syndrome or TBMN? 

Thank you,

I was curious if you could recommend any resources for histology practice? I will be honest I was really struggling in the beginning but am starting to get the hang of it. I feel like with more practice I will feel confident for the exam. Any tips you have would greatly be appreciated!

The concern was about the time frame of nephritic syndrome versus RPGN, since nephritic syndrome (particularly in cases like PSGN) can have an acute onset and RPGN also has an acute time frame. The difference, though is that RPGN has an acute onset of renal failure, while the less aggressive nephritic diseases may have acute onset of nephritic syndrome, but may never progress to renal failure or may do so over a prolonged period. It is the rapid progression to acute renal failure that sets RPGN apart.

As a refresh, anything involving immune complexes or the our immune system in automatically cause inflammation?

Greetings Dr. Ensign, 

I hope this email finds you well. 

I've used resources to help with my confusion, but I could use some help. 

A frequent topic of discussion is "Proliferative Pattern" as seen in APSGN. What does that mean? Does that just refer to the presence of endothelial and mesangial cells? 

What is the best way to distinguish between cells of the capillaries and the mesangial cells as seen in the picture I am attaching, in H&E staining?

I try to keep this in mind: in the glomerulus we have capillaries with an endothelium, glomerular basement membrane, and an epithelium. Spread throughout those capillaries are the mesangial cells. But once I see the stains everything goes out the window! 

Any tips are helpful! 

Thank you! 

To piggyback off my earlier [question], when it says “mesangial proliferation” does that refer to hypercellularity? 

Hello Dr. Ensign,

I have a question regarding GFR and diabetic nephropathy. I understand that a decreased GFR is seen in all renal diseases. However, I was listening to a USMLE review podcast on my way home from the school, the lecturer said that in very early stage of diabetic nephropathy, you can an increased GFR due to atherosclerosis of the efferent arteriole, creating a back pressure on the glomerulus, therefore, hyperfiltration in the beginning, and then GFR goes down like in all other renal disease. I did a quick research on UpToDate, and it seems like hyperfiltration can be present in DM patients. I would like to double check with you to see if that’s accurate, and if we should remember it for exam purposes.

Thanks,

• I was wondering how thrombosis, infection, and atherosclerosis cause protein loss resulting in nephrotic syndrome? 

• Also, why does the body increase hepatic lipoprotein synthesis during nephrotic syndrome?