Nephrotic Syndrome Flashcards
_____ have actin filaments that attach to the basement membrane of the glomerular capillaries to govern the diameter of the capillaries.
Mesangial cells
What is nephrin?
It is a protein that extends out from each podocyte foot process to prevent protein from getting into the urine.
Mutations in ____ and/or _____ (proteins of the slit diaphragm) will lead to proteinuria.
nephrin, podocin
Nephrotic syndrome? (5)
- Proteinuria (greater than 3.5 g/d) (protein leak causes high urine protein)
- Hypoalbuminemia (less than 3.0 g/dl) (serum albumin falls because you’re losing albumin in the urine)
- Edema (oncotic pressure falls so fluid starts to move into interstitium)
- Hyperlipidemia (elevated cholesterol)
- Lipiduria (lipids getting into urine)
Nephritic syndrome? (5)
- Decreased renal function
- Hypertension (decreased renal function means salt retention)
- RBC and RBC casts
- Edema
- Proteinuria (less than 3.5 g/d)
Nephrotic syndromes are primarily due to damage of the _____.
What two ways can this happen to cause proteins to leak across the filtration barrier?
podocytes
- The podocyte can be injured which causes it to swell up and the slit diaphragms are disrupted.
- A direct injury or mutation of the slit diaphragm itself.
What kind of edema is seen in nephrotic syndrome?
Pitting edema. You can press it with your finger and it stays indented for a while.
What two mechanisms lead to edema in nephrotic syndrome? Explain the mechanisms.
- Classic mechanism (particularly in children)
Protein is lost in the urine so there is a lower oncotic pressure in blood capillaries. This causes plasma to leak out into the interstitium which causes edema. Furthermore, less volume in the vessels causes the body to release ADH and aldosterone to increase sodium retention to increase fluid retention. This increases the edema as well.
- More common mechanism
There is a primary defect in Na+ excretion in the distal tubule which causes sodium retention and edema. The low serum albuin also contributes to this effect. However, with this mechanism, there isn’t a low serum volume.
The big difference is that in the classic mechanism, the patient is edematous with a low serum volume and in the more common mechanism the patient is edematous with a high serum volume.
Nephrotic syndrome causes lipiduria. What do lipids look like under polarized light? (2)
“maltese crosses” and “oval fat bodies”
What are 3 additional complications of nephrotic syndrome?
- Hypercoagulable state
- When there is low serum albumin, the liver starts to kick out every protein that it can make. This includes coagulation factors (fibrinogen, factors V, VIII, IX, and X).
- You can lose anti-thrombin III in the urine.
- Increased platelet aggregation to stimuli (hyperactivated platelets)
- Infections
- Loss of immunloglobulins (particularly IgG) and complement proteins (factor B) increases risk for bacterial infections (e.g. peritonitis, pneumonia, etc)
- Decreased Vitamin D levels (loss of vitamin D binding protein)
What is general management of nephrotic syndrome? (6)
- Low salt diet (reduce fluid retention)
- Diuretics (reduce fluid retention)
- BP control
- Cholesterol lowering drugs
- ACE inhibitors (dilation of efferent arterioles causes less glomerular pressure which decreases proteinuria. This does drop GFR a tiny bit but it’s worth the decrease in proteinuria.)
- Vitamin D (25-OH Vit D) replacement.
True or False: Hereditary nephrotic syndrome is typically seen in adults
FALSE
Hereditary nephrotic syndromes are typically seen in children and young adults. It is typically not seen after the age of 25.
What is the etiology of hereditary nephrotic syndrome?
Mutations of slit diaphragm proteins– Nephrin and/or podocin
What is typicaly presentation of hereditary nephrotic syndrome?
Typically seen in children. Sometimes in young adults but not over age of 25.
Presents with ascites, edema, and failure to thrive
If you see high protein in amniotic fluid during pregnancy, what nephrotic syndrome would be on the differential dx?
Hereditary nephrotic syndrome.
What is treatment for kids with hereditary nephrotic syndrome?
Keep them alive long enough to put them on dialysis (usually after 2 months of age) and then when they get to a certain age (usually 2 years), they can get a kidney transplant which cures their disease.
These kids typically don’t respond to treatment since it’s a mutation but the transplant will cure them.
True or False: Minimal change disease typically occurs in children and presents with dramatic and sudden weight gain.
True
What is typical presentation for minimal change disease nephrotic syndrome? (4)
Edema
Ascites
Weight Gain
Normal blood pressure
What is typical age of incidence for minimal change disease (nephrotic syndrome)?
2-10 y/o
What are the lab findings for minimal change disease (nephrotic syndrome)? (4)
- Renal function normal or slightly depressed
- Urinalysis with 4+ protein
- hyaline casts
- microscopic hematuria is rare.
Minimal change disease (a nephrotic syndrome) can be sometimes associated with what 3 things?
- history of allergy
- hodgkin’s lymphoma
- nonsteroidal drugs (idiosyncratic reaction)
What is the pathophysiology of minimal change disease?
The proposed mechanism is that there is something in their blood (a circulating factor) that is triggering podocyte injury disrupting the slit diaphragm and causing proteinuria.
True or False: Minimal change disease (a nephrotic syndrome disease) is difficult to cure.
False
It’s easily treated. Patients are put on corticosteroids (prednisone) and improve quickly. Within weeks to months, the urine protien drops to normal levels. However, some patients relapse. Relapses are treated the same way but if they relapse more than a couple times, you want to give a short course of oral cytoxan (12 weeks).
What does minimal change disease look like under light microscopy, electron microscopy, and immunofluorescence?
Basically, everything is normal except for foot process fusion in electron microscopy.
With light microscopy, the glomerulus looks normal.
With Immunofluorescence, there aren’t any findings.
With electron microscopy, there is foot process fusion.
The fused foot processes just show that the podocytes are damaged. So, some cross sections will show the fused foot processes while other cross sections will have nothing appearance of podocytes at all. This was in response to someone asking “if they are fused, how to proteins pass?”
Recently discovered, the podocytes are not just cells that hold back proteins from crossing the filtration barrier, they are actually antigen presenting cells. How can this be used to differentiate between minimal change disease and other nephrotic diseases?
Antigen CD80 is highly expressed on the podocytes in minimal change disease. When patients are treated with prednisone, the CD80 expression drops dramatically.
CD80 is actually excreted in the urine and you can detect it to know that it’s minimal change disease.
You find CD80 antigens in the urine. What is the disease?
Minimal change disease
HIV nephropathy looks slightly different from other FSGS in histologic findings. What are the 2 characteristic findings?
- Tubular dilation (microcysts)
- Reticulo-endothelial inclusions
What are findings on light, IF, silver stain, and EM for membranous nephropathy?
Light - thick glomerular basement membrane
IF - granular deposits
Silver stain - projections (little spike things)
EM - subepithelial deposits
Low serum complements are in both type 1 and type 2 membranoproliferative glomerulonephritis. What’s the difference between the two?
Type 1 has low C3 and C4.
Type 2 has low C3 but normal C4 (due to alternative pathway of complement due to presence of C3 nephritis factor)
