Pathology - S2B2 - Kidney 2

Front 1

This is the most common form of Acute Glomerulonephritis

Back 1

IgA Nephropathy = Berger Disease

Front 2

What is the most common age group for IgA Nephropathy?

Back 2

Young adults = 15-30 yoa

Front 3

Describe the pathology of IgA Nephropathy

Back 3

Focal and segmental glomerulopathy caused by deposition of IgA in the Mesangium

Front 4

What are the clinical manifestations of IgA Nephropathy?

Back 4

Protean manifestations:
-40% asymtomatic microscopic hematuria
-40% bouts of macro hematuria
-10% nephrotic syndrome
-10% renal failure

**many present with recurrent hematuria (red/cola-colored urine) 1-2 days after a respiratory infection

Front 5

What is the histology of IgA Nephropathy?

Back 5

Focal proliferative glomerulonephritis with diffuse mesangial widening

Front 6

A 15-year old Asian-American boy presents with red-colored urine. After a history, you are informed that he is suffering from a strange flu-like syndrome that began 2 days earlier consisting of vomiting, myalgias, arthralgias, and fever

Back 6

IgA Nephropathy
-postinfectious disease (usually respiratory infection)
-Nephritic type syndrome
-most commonly seen in young adult males

Front 7

Synonym for Crescentic Glomerulonephritis

Back 7

Rapidly Progressive Glomerulonephritis

Front 8

List 4 causes of Crescentic Glomerulonephritis

Back 8

1. Anti-GBM nephritis = Goodpasture's Syndrome
2. ANCA granulonephritis = Wegener Granulomatosis, Microscopic Polyarteritis nodosa, Churg-Strauss Syndrome
3. Immune-complex Glomerulonephritis = Henoch-Schonlein purpura, Cryoglobulinemia
4. Non-immune

Front 9

What is important with Crescentic Glomerulonephritis?

Back 9

You must diagnose and treat patients ASAP, or they'll lose both kidneys within a couple weeks

Front 10

What is the cause of Crescentic Glomerulonephritis in 50% of the cases?

Back 10

Post-streptococcal etiology

Front 11

When auto-antibodies are more active when the blood is cold

Back 11

Cryoglobulinemia

Front 12

List the properties of Anti-Glomerular Basement Membrane Antibody Glomerulonephritis

Back 12

1. Rapidly Progressive GN mediated by antibody
2. Antibody is to Collage type IV
3. Linear IF
4. Fibrinoid necrosis of GBM
5. Crescentic GN
6. Goodpasture Syndrome

Front 13

ANCA granulonephritis that does not have granular deposits on Immunofluorescence

Back 13

Wegener granulomatosis

Front 14

What does ANCA Glomerulonephritis begin as?

Back 14

Necrotizing GN --> becomes Crescentic

Front 15

ANCA is found in serum and binds to what?

Back 15

PMN myeloperoxidase and Proteinase 3

Front 16

Besides IgA Nephropathy, what other disease is characterized by a deposition of IgA in the Glomeruli?

Back 16

Henoch-Schonlein Purpura

Front 17

This disease has no immune deposits in the glomeruli, responds to immunosuppression, and is associated with small vessel polyangiitis

Back 17

ANCA Glomerulonephritis
- Wegener Granulomatosis

Front 18

List the features of Nephrotic Syndrome

Back 18

1. Proteinuria
2. Hypoalbuminemia
3. Generalized Edema
4. Hyperlipidemia = due to increase in lipoprotein synthesis
5. Lipiduria

Front 19

List the diseases associated with Nephrotic Syndrome

Back 19

1. Minimal change disease
2. Membranous Glomerulonephritis
3. Focal Segmental Glomerulosclerosis
4. Diabetic Nephropathy

Front 20

What are 2 other terms for Minimal Change Glomerulonephrpathy?

Back 20

1. Lipoid nephrosis

2. Nil disease

Front 21

This is the most common cause of Nephrotic Syndrome in Children

Back 21

Minimal Change Glomerulopathy

Front 22

What is the pathology of Minimal Change Glomerulopathy?

Back 22

Under EM there is fusion of epithelial (podocyte) foot processes

**Light Microscope and Immunofluorescence show normal glomeruli

Front 23

What is the treatment for Minimal Change Glomerulopathy?

Back 23

Steroids (prednisone)

Front 24

A 4-year-old boy presents to the emergency with a 1-week history of generalized edema and fatigue. You history reveals that he suffered from a viral URI 1 week before the visit. Serum and urine studies show massive Proteinuria, hyperlipidemia, hypoalbuminemia. What pathology would you expect to see?

Back 24

EM showing fusion on epithelial foot processes

= Minimal Change Glomerulopathy

Front 25

Nephrotic syndrome associated with heroin use, morbid obesity, Sickle Cell anemia, and HIV infection

Back 25

Focal Segmental Glomerulosclerosis

Front 26

Nephrotic syndrome that does not respond to Steroid treatment and most patients progress to ESKD in 5-10 years

Back 26

Focal Segmental Glomerulosclerosis

**if HIV related -> ESKD in 1 year
**if child is affected, may take 20 yrs to develop ESKD

Front 27

What is the pathology seen in Focal Segmental Glomerulonephritis?

Back 27

- Sclerosis within Capillary tufts of deep juxtaglomerular glomeruli with Focal distribution and Segmental Distribution
-Hyalinosis = deposition of hyaline masses

*Focal = involves some, but not all, glomeruli
*Segmental = involves part of the glomerulus

Front 28

Most common cause of Nephrotic Syndrome in Adults

Back 28

Focal Segmental Glomerulosclerosis

Front 29

Nephrotic syndrome that has Immune-complex deposition that causes basement membrane thickening

Back 29

Membranous Nephropathy

Front 30

What is the cause of Primary Membranous Nephropathy?

Back 30

Unknown

Front 31

What is the cause of Secondary Membranous Nephropathy?

Back 31

1. SLE
2. HBV, HCV, & syphillis
3. Drugs = Penicillamine
4. Malignancy = tumor antigens

**Immune-complexes deposit in kidney --> Subepithelial

Front 32

What is the pathology seen under light microscope in Mebranous Nephropathy?

Back 32

1. Diffuse membrane-like thickening of the capillary walls

2. Basement membrane "spike-and-dome" appearance is seen in Silver Methenamine stain

Front 33

A 40-year-old woman with a history of SLE presents to your office with a CC of increased swelling in her legs. She had been referred by her primary care physician who suspected a secondary illness to her lupus. Recent lab studies show proteinuria, hypoalbuminemia, hyperlipidemia, and hypercholesterolemia. You suspect that a renal biopsy would demonstrate immune-complex deposition on electron microscopy as well as "spike and dome" appearance on silver methenamine stain

Back 33

Membranous Nephropathy

Front 34

What pathology is seen on EM in Membranous Nephropathy?

Back 34

Immune-comple deposition in Subepithelial locations

Front 35

What is the treatment for Membranous Nephropathy?

Back 35

No treatment -> is a slowly progressive disorder

Front 36

What pathologies does Diabetic Glomerulosclerosis cause?

Back 36

1. Diffuse global thickening of the basement membrane
2. Nodular sclerosis (Kimmelstiel-Wilson nodules)
3. Arteriosclerosis --> HTN
4. Trapping of serum proteins

Front 37

Kimmelstiel-Wilson nodules

Back 37

Diabetic Glomerulosclerosis

= nodular accumulations of mesangial matrix material

Front 38

What is the clinical manifestation of Diabetic Nephropathy?

Back 38

Proteinuria = major manifestation

**Nephrotic syndrome
- severe proteinuria
- Hyperlipidemia
- Lipiduria

Front 39

Leading cause of chronic renal failure in the US

Back 39

Diabetic Glomerulosclerosis

Front 40

List the 4 diabetic kidney diseases

Back 40

1. Glomerulosclerosis

2. Arteriosclerosis = thickened hyaline walls with narrow lumens --> HTN

3. Pyelonephritis = high concentrations of sugar in the interstitium promotes bacterial growth

4. Papillary necrosis = when the pyramid sloughs off and goes down into the renal pelvis

Front 41

What is Primary Amyloidosis?

Back 41

Deposition of AL amyloid from Multiple Myeloma

**AL = amyloid light chain derived from Bence-jones proteins

Front 42

What is Secondary Amyloidosis?

Back 42

deposition of AA amyloid in chronic suppurative conditions, such as purulent osteomyelitis or bronchiectasis

Front 43

Where are Amyloid deposits found in the kidney?

Back 43

1. Glomeruli (mesangium, GBM)

2. Arterioles

3. Tubular basement membranes

Front 44

What are the clinical manifestations of Amyloidosis?

Back 44

1. Nonselective proteinuria (100% of cases)

2. Nephrotic syndrome (60% of cases

3. Renal failure develops over 2-5 yrs

4. Kidneys infiltrated with Amyloid become large!!!

Front 45

List 5 causes of Nephrotic Syndrome

Back 45

1. Minimal Change disease
2. Focal and Segmental Glomerulosclerosis
3. Membranous Nephropathy
4. Diabetes Mellitus
5. Amyloidosis

Front 46

IgA Nephropathy

Focal proliferative glomerulonephritis with diffuse mesangial widening
-Focal & Segmental mesangial widening

-Hematuria

Back 46

What Nephritic Syndrome is this?

How do you know?

What would be the usual presentation with this?

Front 47

IgA Nephropathy
-IgA is deposited mainly within the Mesangium
-Focal Proliferative Glomerulonephritis with diffuse mesangial widening

Back 47

What Nephritic Syndrome would this be?

Front 48

IgA Nephropathy (Berger Disease)
-MESANGIAL deposits of IgA and C3

Back 48

What Nephritic Syndrome is this?

Front 49

IgA Nephropathy = proliferative mesangial disease
-there are 2 mesangial cells
-normally there is 1 mesangial cell per 3 capillary loops

Back 49

What is this schematic showing?

Front 50

Rapidly Progressive Glomerulonephritis = Crescentic Glomerulonephritis
-crescent-shaped proliferation of parietal epithelial cells encroaching on the glomerulus

Back 50

What is this Nephritic Syndrome?

Front 51

Goodpastures's Syndrome

Type II = Cytotoxic = Auto-Ab's directed toward GBM

Back 51

What is this typical of?

What type of Hypersensitivity Reaction?

Front 52

Goodpasture Syndrome
-Anti-GBM Ab's cause focal fibrinoid necrosis where rupture occurs and fibrin leaks out thru the BM

Back 52

Explain this slide

Front 53

Male dominant Rapidly Progressive Glomerulonephritis Nephritic Syndrome with a LINEAR IF

Back 53

Goodpasture Syndrome
-fibrinoid necrosis of GBM

Front 54

Goodpasture Syndrome
-hypercellularity
-crescents
-fibrin

Back 54

What disease?

Front 55

Goodpasture Syndrome
-glomerulus is hyalinized due to Anti-GBM Ab's = Hyaline leaks out from the capillaries

Back 55

What disease?

Front 56

-Goodpasture Syndrome

- Capillary loops are being compressed by the Crescent

-GFR will decrease to ZERO in a couple weeks = Rapid Progressive Glomerulonephritis

Back 56

What disease?
What process is happening?
What does this cause?

Front 57

Normal Kidney
-one mesangial cells per 3 capillary loops

Back 57

What is this?

Front 58

Minimal Change Nephropathy
-fused foot processes of the epithelial cells

Back 58

Pathology seen on the right

Front 59

Minimal Change Disease (Lipoid Nephrosis = Nil Disease)
-Fused foot processes

Back 59

What Nephrotic Syndrome is this?

Front 60

Focal Segmental Glomerulosclerosis
-Sclerosis within capillary tufts of deep JG glomeruli

HIV, AIDS, Obesity, Sickle Cell

Back 60

What Nephrotic Syndrome is this?

What is it associated with?

Front 61

Membranous Nephropathy

Back 61

Nephrotic Syndrome associated with these 2 pathologies

Front 62

Membranous Nephropathy
-diffuse capillary wall thickening and basemement membrane thickening
-there is NO hypercellularity

Back 62

What Nephrotic Syndrome is this?

Front 63

Membranous Nephropathy
-capillary wall and basement membrane thickening
-NO hypercellularity

Back 63

What Nephrotic Syndrome is this?

Front 64

Membranous Nephropathy
-immune-complex deposition in SUBEPITHELIAL locations

Back 64

What Nephrotic Syndrome is this?

Front 65

IgG and C3 deposits

Back 65

This is Membranous Glomerulonephropathy. What is deposited in the Subepithelium?

Front 66

What is deposited in the Sclerotic lesions in Focal Segmental Glomerulosclerosis?

Back 66

IgM & C3

**vs. IgG/C3 for Membranous Nephropathy

Front 67

Membranous Glomerulonephritis
-Spike-and-Dome appearance on Silver Methenamine stain

Back 67

What Nephrotic Syndrome is this?

Front 68

Diabetic Glomerulosclerosis

Nodular Sclerosis = Kimmelstiel-Wilson nodules
-nodular accumulation of mesangial matrix material

Back 68

What Nephrotic Syndrome is this?

What is the pathology?

Front 69

Diabetic Nephropathy
-Diffuse Glomerulosclerosis = diffusely distributed increase in mesangial matrix
-Hyalinization of Efferent and Afferent Arterioles

Back 69

What Nephrotic Syndrome is this?

Front 70

Hyalinized Arterioles due to Diabetic Nephropathy

Hypertension

Back 70

What is seen here?
What is the consequence?

Front 71

1. Necrotic Renal Papilla

2. Diabetic nephropathy

3. Drops off and falls into Calyx -> RENAL COLIC = contraction of the ureter b/c it contains foreign material

Back 71

What is this?
What is the cause?
How might it manifest clinically?

Front 72

Amyloidosis

Congo Red stain which when polarized under the light microscope results in an APPLE GREEN BIREFRINGENCE pattern

Back 72

What is the cause of this?
What stain?

Front 73

Accumulations of cells composed of proliferating Parietal Epithelial Cells and infiltrating Leukocytes

Back 73

Crescents

Front 74

What has proliferated to form Crescents in Rapidly Progressive GN?

Back 74

Parietal epithelial cells

Front 75

Type of Glomerulonephritis defined by the lack of anti-GBM Ab's or Immune-complexes by immunofluorescence and EM. Most patients with this type of Rapidly Progressive GN have Antineutrophil Cytoplasmic Antibodies (ANCA), which play a role in some vasculitides

Back 75

Pauci-immune = ANCA granulonephritis
-Wegener Granulomatosis (c-ANCA)

Front 76

Nephritic that is usually progressive over a matter of weeks and culminates in severe oliguria

Back 76

Crescentic GN = Rapidly Progressive GN

Front 77

List the diseases associated with Nephritic Syndrome

Back 77

1. Post-streptococcal GN
2. Rapidly Progressive GN
3. Membranoproliferative GN
4. IgA Nephropathy

Front 78

Unlike Nephritic Syndrome, what 3 things does Nephrotic Syndrome not have?

Back 78

1. Hematuria
2. Oliguria
3. Hypertension

Front 79

Unlike Nephrotic Syndrome, what 2 things does Nephritic Syndrome not have?

Back 79

1. Hyperlipidemia

2. Lipiduria

Front 80

What is the initial event leading to Nephrotic Syndrome?

Back 80

derangement in Glomerular Capillary Walls resulting in INCREASED PERMEABILITY TO PLASMA PROTEINS
-low-weight proteins, such as albumin

Front 81

What is the initial event leading to Nephritic Syndrome?

Back 81

inflammatory RUPTURE of glomerular capillaries with resultant bleeding into the urinary space

Front 82

Sclerosis of some, but not all, glomeruli & only a portion of the capillary tuft is involved

Back 82

Focal Segmental Glomerulosclerosis

Front 83

Membranous Glomerulonephropathy
-diffuse thickening of capillary wall
-NO cellular proliferation

Back 83

What Nephrotic Syndrome is this?

Front 84

Diabetes causes Hyalinizing Arteriolar Sclerosis and increases the susceptibility to the development of these 2 Kidney lesions

Back 84

1. Pyelonephritis

2. Papillary Necrosis

Front 85

Focal proliferative Glomerulonephritis with Diffuse Mesangial widening

Back 85

IgA Nephropathy = Berger Disease