Pathoma Nephrotic Syndrome

Question 1

Proteinuria means what?

Answer 1

More than 3.5 grams per day

Question 2

When we are losing a lot of protein in the urine, what is one of the first things we think of and why? What does it lead to?

Answer 2

Hypoalbuminemia, low albumin, which is the main protein we are losing.

Low albumin means low oncotic pressure which means fluid retention = edema

Question 3

Hypogammaglobuinemia and result?

Answer 3

We lose gammaglobulin, which will lead to an increase in infection

Question 4

Why is a patient with high protein excretion hypercoagulable?

Answer 4

The body will preferentially lose Antithrombin III, leading to more coagulation

Question 5

What other conditions are caused by low protein and why?

Answer 5

Hyperlipidemia and hypercholesterolemia. Blood becomes thin, so the body throws fat and cholesterol at it to beef it up

Question 6

Most common cause of nephrotic syndrome in children

Answer 6

MCD - Minimal Change Disease

Question 7

What other condition do we associate with MCD?

Answer 7

Hodgkin Lymphoma

Question 8

Describe the layers of the glomerular filtration barrier

Answer 8

Endothelial cells with a basement membrane on top and the feet processes of the podocytes on top of that (also called the epithelial layer

Question 9

What do we lose with MCD?

Answer 9

We lose the foot processes, or rather, they flatten out and take up a lot more space

Question 10

What causes the damages seen in MCD?

Answer 10

Cytokines

Question 11

H and E for MCD?

Answer 11

Normal Glomeruli!

Also no immune complex deposits and negative for Immunofluorescence

Question 12

Wait how the hell do we see MCD…

Answer 12

Effacement of foot processes on EM

Question 13

MCD direct protein effects

Answer 13

Selective proteinuria (loss of albumin but not immunoglobulin)

Question 14

Treatment for MCD

Answer 14

Excellent response to steroids (damage is mediated by cytokines from T cells)

Question 15

Focal segmental glomerulonephrosis (FSGS)?

Answer 15

Most common cause of nephrotic syndrome in Hispanics and African Americans

Question 16

What do we associate with causes for FSGS?

Answer 16

HIV, heroin use and sickle cell disease

Question 17

H and E, EM and IF/Immune complex results for FSGS

Answer 17

Focal and segmental sclerosis on H and E

Effacement of foot processes on EM

No immune complexes so negative IF

Question 18

How can we distinguish FSGS from MCD if they look the same on all the histo tests?

Answer 18

FSGS is segmental, look at other areas of the glomerulus.

Also, focal only, so not all of the glomeruli will be affected

Also, you’ll see a pink sclerosis

Question 19

Relate MCD to FSGS

Answer 19

If you are too late or the steroids dont work to stop MCD, your patient will develop FSGS. This will then progress to chronic renal failure

Question 20

Membranous nephropathy is seen in who?

Answer 20

Most common cause of nephrotic syndrome in caucasian adults.

Question 21

What is membranous nephropathy associated with?

Answer 21

Hepatitis B/C, solid tumors, SLE (important because this is how lupus patients can die) or drugs like NSAIDs and penicillamine

Question 22

H and E, IF, and EM for membranous nephropathy

Answer 22

H and E = thick glomerular basement membrane (membranous)

Granular IF due to immune complex deposition

EM = subepithelial deposits with ‘spike and dome’ appearance on EM (dome over the immune complex deposits and spikes in between))

Question 23

Discuss H and E and IF for Membranoproliferative glomerulonephritis

Answer 23

Thick capillary membranes on H and E, often with “tram-track” appearence

Due to immune complex deposition like Membranous nephritis so you’ll see that granular IF again)

Question 24

Discuss the etiology behind the “tram track” appearence of Membranoproliferative glomerulonephritis

Answer 24

So remember those balls of complexes we had in between the podocytes? If they happen too close to the mesangial cells, which are holding these sections together, the mesangial cell will project part of its cytoplasm (proliferate) out to the complex to cut it in half. These two pieces look like two lines after the break

Question 25

Discuss the subtypes of membranoproliferativeglomeruonephritis and what they are associated with

Answer 25

Type I = subendothelial - underneath the epithelial cells and basement membrane- Associated with HBV and HCV and also, more commonly associated with tram track!!

Type II = intramembranous in between the podocytes but still in the membrane - Associated with C3 nephritic factor

Question 26

Discuss C3 nephritic factor and how it causes Type II membranoproliferative glomerulonephritis

Answer 26

C3 convertase is rapid and breaks apart quickly, turning C3 into C3a and b, which is your complement pathway. The factor holds the enzyme together continuously, so complement is overacting in Type II.

You’ll see decreased C3 and damage to the kidney

Question 27

How does Diabetes Mellitus cause nephrotic problems?

Answer 27

High serum glucose leads to non enzymatic glycosylation of vascular basement membranes, making it leaky, resulting in hyaline arteriolosclerosis = thickening of the vascular wall

Question 28

In regards to DM and its effect on the kidneys, ___ arteriole is more affected than the ____ arteriole, leading to a higher ___ ___ ___.

Answer 28

Efferent more than afferent, high Glomerular filtration pressure

Question 29

What is special about the non enzymatic glycosylation seen in DM?

Answer 29

It is the first change in this disease!

Question 30

Hyperfiltration pressure seen with DM on the kidney leads to what?

Answer 30

Microalbuminuria which eventually progresses to nephrotic syndrome

Question 31

How do we characterize this glomerular damage caused from DM?

Answer 31

We’ll see sclerosis of mesangium and formation of Kimmelstiel-Wilson nodules

Question 32

___ ___ slow progression of hyperfiltration-induced damage

Answer 32

ACE inhibitors

Question 33

Most common organ affected by Systemic amyloidosis

Answer 33

Kidney

Question 34

Etiology behind Systemic Amyloidosis

Answer 34

Amyloid deposits in mesangium resulting in nephrotic syndrome

Question 35

What particular test can we use to see secondary amyloidosis

Answer 35

We will see apple-green birefringence under polarized light