Nephrotic Syndrome Flashcards
What is the cause of most nephrotic syndromes?
Most are idiopathic!
What characterizes most glomerular disorders (nephrotic syndrome)?
Proteinuria >3.5 g/day
What four things does the proteinuria in nephrotic syndrome result in?
- Hypoalbuminemia
- Hypogammaglobulinemia
- Hypercoagulable state
- Hyperlipidemia and Hypercholesterolemia
What is the major protein in the blood?
Albumin
What does Hypoalbuminemia cause?
Dec. albumin –> Dec. osmotic pressure (in blood vessel) –> Inc. fluid in tissue –> pitting edema
What does Hypogammaglobulinemia cause?
Loss of gammaglobulin –> Increased risk of infection
What causes the Hypercoagulable state in nephrotic syndromes?
Loss of Antithrombin III
What does Hyperlipidemia and Hypercholesterolemia cause in nephrotic syndromes?
It may result in fatty casts in the urine
What creates the Hyperlipidemia and Hypercholesterolemia in nephrotic syndromes?
Loss of protein (hypoalbuminemia) –> Blood becomes thin –> liver throws out fat and cholesterol in blood to thicken it up
What is the most common cause of nephrotic syndrome in children?
Minimal Change Disease (MCD)
What can cause/be related to Minimal Change Disease (MCD)?
Usually idiopathic –> may be associated with Hodgkin lymphoma
What makes up the three layers of the glomerular filtration barrier?
- Endothelial cells
- Basement Membrane
- Epithelial cells/Foot processes of podocytes
What do you see on H&E stain of MCD?
- Normal glomeruli
- Lipid may be seen in the proximal tubule cells
What is seen on electron microscopy (EM) of MCD?
Effacement of foot processes
What is seen on Immunofluorescence of MCD?
No immune complex deposits –> Negative IF
What type of proteinuria is seen in MCD?
Selective proteinuria = loss of albumin but no immunoglobulin
How is MCD treated? What is the response like?
Excellent response to steroids
-Only nephrotic syndrome that responds this well
Why is MCD treated will with steroids? What mediates the damage caused by the disease?
Damage is mediated by cytokines and T cells
What causes MCD in Hodgkin Lymphoma?
Massive production of cytokines by Reed-Sternberg Cells!
What is the most common cause of nephrotic syndrome in Hispanics and African Americans?
Focal Segmental Glomerulosclerosis (FSGS)
What is the cause of Focal Segmental Glomerulosclerosis (FSGS)?
Usually idiopathic
What might FSGS be associated with?
HIV, heroin use, and sickle cell disease
If you have an HIV patient that develops nephrotic syndrome, what does this tell you?
He/she has FSGS
What does glomerulosclerosis look like?
Dense, pink collagen deposition
What does FSGS show on H&E stain?
Focal (only some glomeruli) and segmental (involving only part of the glomerulus) sclerosis.
If MCD doesn’t respond to steroids, what might it become?
FSGS
What is seen on EM in FSGS?
Effacement of foot processes
What is seen on IF of FSGS?
- No immune complex deposits
- Negative IF
How do you treat FSGS? What is the response like?
Poor response to steroids
What does FSGS progress to?
CRF (chronic renal failure)
What is the most common cause of nephrotic syndrome in Caucasian adults?
Membranous Nephropathy
What causes Membranous Nephropathy?
Usually idiopathic
What conditions may be associated with Membranous Nephropathy?
Hepatitis B or C, Solid tumors, SLE or drugs (e.g. NSAIDs and penicillamine)
What is the most common cause of death in SLE?
Renal failure!
What is seen in Membranous Nephropathy on H&E?
Thick glomerular basement membrane
What causes the thick glomerular basement membrane in Membranous Nephropathy?
Immune complex deposition
What is seen on IF of Membranous Nephropathy?
Granular IF - due to Immune Complex Deposition
What do you see on EM of Membranous Nephropathy?
Subepithelial deposits with ‘spike and dome’ appearance.
Where do immune complexes deposit in Membranous Nephropathy?
Subepithelial
How is Membranous Nephropathy teated? How does it respond?
Poor response to steroids
What does Membranous Nephropathy progress to?
CRF (chronic renal failure)
What nephritis can cause Nephrotic, Nephritic and/or both syndromes?
Membranoproliferative Glomerulonephritis
What is seen on H&E of Membranoproliferative Glomerulonephritis?
Thick glomerular basement membrane, often with a ‘tram-track’ appearance
What causes the thick glomerular basement membrane in Membranoproliferative Glomerulonephritis?
Immune complex deposition
What is seen in IF of Membranoproliferative Glomerulonephritis?
Immune complex deposition (granular IF)
What are the two types of Membranoproliferative Glomerulonephritis?
- Type I
2. Type II
What are the two types of Membranoproliferative Glomerulonephritis based on?
Location of deposits
Where are the deposits in Type I Membranoproliferative Glomerulonephritis?
Subendothelial
What is Type I Membranoproliferative Glomerulonephritis associated with?
HBV and HCV (these are more often associated with tram-track appearance)
Where are the deposits in Type II Membranoproliferative Glomerulonephritis?
Intramembranous
What is Type II Membranoproliferative Glomerulonephritis also known as?
Dense deposit disease
What is Type II Membranoproliferative Glomerulonephritis associated with?
C3 Nephritic factor
What is C3 Nephritic factor and what does it do?
It’s an autoantibody that stabilizes C3 convertase —> leads to overactivation of complement –> Inflammation –> Low levels of circulating C3
What does C3 convertase do?
Converts C3 to C3a and C3b
What does Membranoproliferative Glomerulonephritis have a poor response to?
Steroids
What does Membranoproliferative Glomerulonephritis progress to?
CRF (chronic renal failure)
What causes the tram-track appearance of the basement membrane in Membranoproliferative Glomerulonephritis?
Mesangial cells grow out in-between Immune complexes/basement membrane, dividing them into strips and making them look like two tracks.
What happens to the basement membrane in Diabetes Mellitus?
High serum glucose –> non enzymatic glycosylation of the vascular basement membrane (sugar sticking to basement membrane) –> Hyaline Arteriolosclerosis
What type of arteriolosclerosis is associated with Diabetes Mellitus?
Hyaline Arteriolosclerosis
What glomerular arteriole is more affected in Diabetes Mellitus?
Efferent arteriole is more affected.
What does arteriolosclerosis of the efferent arteriole cause?
High glomerular filtration pressure
What does hyperfiltration injury in Diabetes Mellitus lead to?
Microalbuminuria
What does the increased pressure in the efferent arteriole in Diabetes Mellitus eventually progress to?
Nephrotic syndrome
What characterizes Nephrotic syndrome in Diabetes Mellitus?
- Sclerosis of the mesangium
- Formation of Kimmelstiel-Wilson nodules
What drugs slow the progression of hyper filtration induced damage in Diabetes Mellitus?
ACE Inhibitors
How does arteriolosclerosis lead to nephrotic syndrome in Diabetes Mellitus?
Inc. GFP –> Sclerosis –> Nephrotic syndrome
What does Angiotensin II exacerbate that ACE inhibitors stop?
Narrowing of the efferent arteriole
What is the most commonly involved organ in Systemic Amyloidosis?
Kidney!!
How does Systemic Amyloidosis cause Nephrotic syndrome?
Amyloid deposits in the mesangium –> results in nephrotic syndrome
What stain is used to characterize Systemic Amyloidosis?
Congo red
What appearance does Systemic Amyloidosis have with Congo red stain?
Apple-green birefringence under polarized light
