Summary Slides and Pics Nephrotic II

Question 1

Minimal Change Disease
• effectiveness of Tx option?
• Biopsy appearance on LM, IF, EM?

Answer 1

Minimal Change Disease:
• STEROIDS = typical treatment, MCD is steroid responsive

Biopsy:
LM - Normal
IF - Normal
EM - Podocyte Foot Process Fusion (effacement)

Question 2

Focal Segmental Glomerulosclerosis
• effectivness of Tx option?
• Px compared to MCD?

Answer 2

FSGS: TX:
• NOT very responsive to steroid therapy

Px:
• HIGH RISK of developing END STAGE renal disease

Question 3

What happens to nephron mass in SECONDARY FSGS?

Answer 3

• Nephron mass is reduced in secondary FSGS

Question 4

Findings on FSGS biopsy:
• LM
• IF
• EM

Answer 4

LM:
*SCARRING with Obliterated Capillary Lumen
• Areas of Adhesion to Bowman’s Capsule

IF: • NORMAL (aka negative)

EM: • Podocyte Foot Process fusion (effacement)

Question 5

Membranous Nephropathy
• Common Targeted Antigen
• Risk of Renal Failure

Answer 5

Mem. Neph. Targeted Antigen:
• M-type phospholipase A2
• Progressive to renal failure in 30%

Question 6

Findings on Membranous Nephropathy Biopsy.
• LM, IM, EM

Answer 6

LM:
• diffuse thickening of GBM with NORMAL cellularity

IF:
• Fine Granular Staining with IgG and complement

EM:
• SPIKE and DOME subepithelial Deposits

Question 7

What are some secondary causes of the food process effacement seen here?
• Make a Dx. Note this person had no HTN.

Answer 7

MINIMAL CHANGE DISEASE:
• Primary causes: idiopathic as usual
• Secondary causes: Hodkins Lymphoma and NSAIDs

SHOWN below is another picture of Podocyte Effacement

Question 8

would you expect them to have a nephritic or nephrotic syndrome?

Answer 8

NEPHROTIC - seen here is podocyte effacement indicative of Minimal Change Disease or Focal Segmental Glomerulosclerosis
- these are NEPHROTIC syndromes (inflammatory cells are not involved)

Question 9

How does SUPAR work?
• disease association?
• Cells that produce this protein?

Answer 9

SUPAR - associated with FSGS - binds to INTERGRIN and prevents the podocyte from binding Neutrophils and Monocytes

Question 10

Is minimal Change or FSGS shown here?
• how do you know?

Answer 10

Shown here are focal and segmental lesions, since there is VISIBLE damage its NOT Minimal Change Disease

***Minimal Change Disease doesn’t show up on LM or IF - only EM**

Question 11

What are the Key features of this glomerulus with FSGS?

Answer 11

• HYLALINE deposits - remember NEPHROTIC syndromes aka NO inflammatory involvment
• LIPID Droplets
• Thickened Mesangial Matrix

• Capillary Lumina Obliterated

Question 12

Although FSGS is not inflammatory you still see hypercellularity, what is this attributable to?

Answer 12

Hypercellularity seen from FOAMY MACROPHAGES, this increased ENDOCAPILLARY cellularity occludes capillaries

Question 13

What type of FSGS is seen here?
• PX?

• How would you treat this disease?

Answer 13

This is Collapsing Type FSGS. - prognosis = SHITTY

Tx:
• ACE I/ARB - 1st need to control amt of protein going through glomerulus

• Treat Hyperlipidemia
• CORTICOSTEROIDS can be used but will probably be ineffective, you should probably use Calcineurin Inhibitors like Cyclosporin or Tacrolimus

Question 14

If you treat someone’s minimal change disease with steroids and the disease doesn’t remit. what might you suspect?

Answer 14

MCD may have progressed to FSGS which is much more steroid resistant

Question 15

What disease is shown here?
• KEY feature?
• Epidemiology?

• would this tissue be responsive to immunofluorescence why or why not?

Answer 15

Membranous Nephropathy
Key Feature:
• SPIKES on Silver stain

Epidemiology:
• Most common in White Males between 40-60 years of age

IF:
• this tissue would show an IF pattern because IgG4 mediates the disease

Question 16

These are the LM changes associated with Membranous Nephropathy.
• what would you expect to see on EM.
• Common causes of this disease.

Answer 16

**Note: we see THICKENING of the Basement membrane with NO increase in cellularity***

EM:
• Show SubEPIthelial deposits that are Spike and Dome

• see below

Causes:
• Hepatitis B, C, TUMORS, SLE, NSAIDs, Penicillamine

Question 17

T or F: SLE causes disease that create both subepithelial and subendothelial deposits

Answer 17

True

• Subendothelial - Membranous Nephropathy - TYPE V
• Subepithelial - Diffuse Proliferative - TYPE IV

Question 18

What key features are seen here in Post-Streptococcal Glomerulonephritis?

Answer 18

Glomeruli are globally and diffusely enlarged and hypercellular due to neutrophils and macrophages and proliferation of mesangial and endothelial cells

**Everything increases in cellularity and you get inflammatory infiltrate - THIS IS NOT JUST A NEPHROTIC Syndrome

Question 19

What serum immune markers would you expect to be altered in this person with Post-Infectious GN. (IF shown below)

Answer 19

LOW C3 and NORMAL C4 because Alternative Complement is activated

*This is in contrast to PAN associated disease where you see monoclonal IgM proliferation which activates the classical pathway*

SERUM ANTIBODIES to TEST FOR:

• Elevated anti-streptolysin O (ASO) titers if preceded by throat infection
• Elevated Anti-DNAse B titers if preceded by skin infection
• Positive blood culture in sepsis

Question 20

The EM shown here is nearly pathopeumonic for what condition?

Answer 20

Post-Infectious GN

• DOME SHAPED SUBEPITHELIAL HUMPS