Renal Pathology: Glomerular Diseases

Front 1

So let's start with the broadest classifications of Glomerular Diseases?

Back 1

Those w/ Nephrotic Presentation
W/ Nephritic Presentation
Systemic Diseases affecting kidney
Chronic GN

Front 2

Who are the guys presenting w/ Nephrotic Syndrome?

Back 2

Minimal Change
Focal Segmental Glomerulosclerosis
Membranous Glomerulopathy
Membranoproliferative GN

Front 3

Kickers for Minimal Change?

Back 3

KIDS! (2-6 yo's)
minimal change on light microscopy
Uniform and Diffuse foot process effacement on EM
No deposits, no immunofluorescence

Front 4

What is the most common cause of nephrotic syndrome in adults in the U.S.?

Back 4

FSGS

Front 5

Common Association for FSGS?

Back 5

Inherited forms
HIV
heroin addiction
Sickle Cell
Big Fatties

or it can be Secondary...

Front 6

What's screwed up in inherited FSGS?

Back 6

nephrin
podocin
alpha-actinin 4

Front 7

What's up when FSGS is a secondary process?

Back 7

Possibly Focal GN
Possibly adaptive response to renal tissue ablation in advanced disorders (reflux nephropathy, HTN nephropathy, or unilateral renal agenesis)

Front 8

What about FSGS and Congenital Nephrotic Syndromes?

Back 8

CNS of Finnish Type = NPHS1 gene on 19

Steroid-Resistant Nephrotic Syndrome of Childhood Onset = NPHS2 gene on 1

Front 9

Morphology of FSGS?

Back 9

Focal and Segmental Sclerosis
Lipid Droplets and Foam Cells

Front 10

Which type of FSGS is the worst?

Back 10

HIV variant

Front 11

FSGS Immunofluorescence?

Back 11

Focal Fibrin Deposits in areas of sclerosis

Focal IgM and C3

Front 12

FSGS on EM?

Back 12

Loss of foot processes
Epithelial Denudation
Sclerosis
Collapse of GBM

Front 13

What can Membranous Glomerulopathy be secondary to?

Back 13

Drugs
Malignancies
Lupus
Infections (hep, syph, malaria, etc)

Front 14

Morphology for Membranous Glomerulopathy?

Back 14

Uniform, Diffuse thickening of Glomerular Capillaries
No Prolif
Irregular "spikes" on GBM

Front 15

What do you have to do to see the GBM spikes in Membranous Glomerulopathy?

Back 15

Silver Stains

Front 16

IF and Membranous Glomerulopathy?

Back 16

Diffuse, finely granular deposits (lumpy bumpy) of:
C3
IgG
+/- IgM and IgA on cap walls

Front 17

EM and Membranous Glomerulopathy

Back 17

Subepithelial, electron-dense deposits

Front 18

Clinical Presentation of Membranoproliferative GN?

Back 18

Nephritic and/or Nephrotic
i.e. proteinuria +/- hematuria

Front 19

Difference between nephritic and nephrotic?

Back 19

Nephritic = blood and protein (< 3)
Nephrotic = just lots of protein (> 3)

Front 20

MPGN Type 1 vs 2?

Back 20

1: assoiated w/ cryoglobulinemia and hep C

2: Circulating Antibody C3 Nephrotic Factor which activates alt. C' cascade

Front 21

Morphology for MPGN?

Back 21

Diffusely Enlarged, Hypercellular Glomeruli
Prolif of Mesangial Cells and Inc Matrix--> lobular appearance
Thickened GBM --> Tram-Track
Infiltration by leukocytes...occasionally crescent

Front 22

MPGN Type 1 and IF?

Back 22

Granular C3
IgG and early C' components (C1q and C4)

Front 23

EM and MPGN Type 1?

Back 23

Subendothelial electron-dense deposits

Occasionally Mesangial and Subepithelial deposits too

Front 24

MPGN Type II and IF?

Back 24

Irregular granular or linear C3 in GBM and usually in mesangium too (mesangial rings)
IgG usually absent as are C1q and C4

Front 25

MPGN Type II and EM?

Back 25

Sausage Shaped/Ribbon-Like deposits in lamina densa of GBM

Front 26

OK...finally...on to Nephritic Syndromes...who presents this way?

Back 26

Acute Diffuse Proliferative GN
IgA Nephropathy
Thin BM and Alport Syndrome

Front 27

Causes of Acute Diffuse Proliferative GN

Back 27

Immune complexes to exogenous or endogenous Ag

Front 28

Prototype of Acute Diffuse Proliferative GN?

Back 28

Postinfectious GN after Group A Beta-hemolytic Streptococci Infection

Front 29

Presentation of Acute Diffuse Proliferative GN?

Back 29

Nephritic Syndrome: hematuria, oliguria, mild to moderate HTN
1-4 weeks after strep infection of pharynx or skin
Elevated titers of Ab's against strep Ag's
Low Serum C' levels b/c of activation and consumption of cascade

Front 30

Morphology of Acute Diffuse Proliferative GN?

Back 30

Diffusely, Enlarged Hypercellular Glomeruli
Infiltrated by leukocytes
Prolif of endothelial, mesangial cells
Occasional Crescents
Obliterated Cap Lumens
Edema and Infl of Interstitium
Red Cell Casts

geez

Front 31

Acute Diffuse Proliferative GN and IF?

Back 31

Granular Deposits
IgG, IgM, C3
Mesangium and along BM

Front 32

Acute Diffuse Proliferative GN and EM?

Back 32

Sub-epithelial deposits w/ HUMPS
Possibly Sub-endothelial deposits, intra-membranous, and mesangial deposits

Front 33

Most common form of GN in the WORLD?

Back 33

IgA Nephropathy

Front 34

IgA Nephropathy: primary, secondary, ????

Back 34

Can just be Primary
or
Component of Henoch-Schonlein Purpura

Associated w/ liver disease (alcoholic), celiac's, IBD, Yersinia enterocolitis, psoriasis, HIV, etc

Front 35

IgA Nephropathy Morphology

Back 35

DIFFERENT FORMS:
Mesangioproliferative
Proliferative GN (focal/diffuse)
Crescent Formation
Sclerosis (focal/diffuse)

Front 36

IgA Nephropathy and IF?

Back 36

Mesangial IgA deposits
C3, IgG, or IgM may be present in lesser amounts

Front 37

IgA Nephropathy and EM?

Back 37

Deposits in the mesangium

Front 38

Types of Hereditary Nephritis?

Back 38

Alport's
Thin BM Disease

Front 39

What is the most common cause of Benign Familial Hematuria?

Back 39

Thin BM Disease

Front 40

How does Alport's present?

Back 40

Nephritis
Nerve Deafness
Various Eye Disorders (lens dislocation, post. cataracts, corneal dystrophy)

Front 41

How is Alport's inherited?

Back 41

X-linked is most common
rarely Auto Rec or Auto Dom

Front 42

Pathogenesis of Alport's?

Back 42

Defective GBM synthesis via abnormal Collagen Type IV synthesis

Front 43

Difference between pathogenesis of x-linked alport's and auto rec/dom alport's?

Back 43

X-linked: defect in alpha-5 chain of Type IV collagen

Auto Rec/Dom: defect in alpha 3 or 4 chain of Type IV collagen

Front 44

Morphology of Alport's?

Back 44

Interstitial Foam Cells
FSGS, Global Glomerulosclerosis

Front 45

Alports and EM?

Back 45

Diffuse GBM thinning
Splitting and lamination fo lamina densa (basket-weave)

Front 46

Alports and IF?

Back 46

Missing alpha3, alpha4, and/or alpha5 collagen in glomerular and tubular BM's

Front 47

How does Thin BM Disease present?

Back 47

Usually asymptomatic
No hearing of visual abnormalities

Front 48

Morphology of Thin BM Disease?

Back 48

Diffuse Thinning of GBM

Front 49

Pathogenesis of Thin BM Disease?

Back 49

Related to genes encoding alpha3 or alpha4 chains of Type IV Collagen

Most patients are heterozygous for the defective gene. Homozygotes can progress to RF

Front 50

Moving on...Who are the systemic diseases who commonly cause glomerular diseases?

Back 50

Rapidly Progressive GN (crescentic)
Lupus
Diabetes
Amyloidosis

Front 51

Classic picture of Rapidly Progressive GN?

Back 51

Crescents on Histo

Front 52

Progression of Rapidly Progressive GN?

Back 52

Can lead to Severe RF in weeks to months

Front 53

How are Crescents formed?

Back 53

proliferation of parietal cells and migration of inflammatory cells into urinary space

Front 54

Classification of Rapidly Progressive GN?

Back 54

Type 1: Anti-GBM Antibody

Type 2: Immune Complex

Type 3: Pauci-Immune

Front 55

Who are the Type 1 Rapidly Progressive GN?

Back 55

Idiopathic
Goodpasture's

Front 56

Who are the Type 2 Rapidly Progressive GN?

Back 56

Idiopathic
Postinfection
SLE
Henoch-Schonlein Purpura
Others

Front 57

Who are the Type 3 Rapidly Progressive GN?

Back 57

Idiopathic
ANCA associated
Wegener's
Microscopic Polyarteritis Nodosa/Microscopic polyangitis

Front 58

In Type 1 Rapidly Progressive GN, who are the antibodies directed against?

Back 58

Noncollagenous Domain (NC1) of the alpha-3 chain of Type IV Collagen

Front 59

What else can the Type 1 Rapidly Progressive GN antibodies affect?

Back 59

Pulmonary Alveolar BM's--> Goodpastures

Front 60

Type 1 Rapidly Progressive GN and IF?

Back 60

Linear Deposits (along BM)
IgG and C3

Front 61

Type 1 Rapidly Progressive GN and EM?

Back 61

No deposits
GBM Disruptions
Fibrin

Front 62

Morphology of Type 2 Rapidly Progressive GN?

Back 62

Crescentic GN

Front 63

IF for Type 2 Rapidly Progressive GN?

Back 63

Granular Deposits according to underlying disorder

Front 64

EM for Type 2 Rapidly Progressive GN?

Back 64

deposits according to underlying disorder

Front 65

Type 3 Rapidly Progressive GN antibodies?

Back 65

cANCA in wegener's

pANCA in microscopic polyangiits

Front 66

Type 3 Rapidly Progressive GN morphology?

Back 66

crescentic GN

Front 67

Type 3 Rapidly Progressive GN and IF?

Back 67

little or no deposition of immune complexes (pauci-immune)

Front 68

Type 3 Rapidly Progressive GN and EM?

Back 68

None or very few deposits

Front 69

What percent of lupus pts have renal involvment?

Back 69

50-80%

Front 70

Principle mechanism for renal involvement in SLE?

Back 70

Immune Complex deposition in renal structures

Also possible thrombotic process if pt has antiphospholipid antibodies

Front 71

Five Patterns of Lupus Nephritis?

Back 71

Class 1: minimal or no detectable abnormalities
2: mesangial lupus GN
3: Focal Proliferative GN
4: Diffuse Proliferative GN
5: Membranous GN

Front 72

Types of lesions in Lupus Nephritis?

Back 72

Active

Chronic

Front 73

Types of Active Lesions in Lupus Nephritis?

Back 73

GLOMERULI:
hypercellularity
fibrinoid necrosis
crescents
wire loops
leukocyte infiltration
more

TUBULES/INTERSTITIUM
mononuclear infiltration

Front 74

Types of Chronic Lesions in Lupus Nephritis?

Back 74

Glomerulosclerosis
Fibrous Crescents
Interstitial Fibrosis
Tubular Atrophy

Front 75

IF and Lupus Nephritis?

Back 75

FULL HOUSE
IgG, IgA, IgM
C3, C1q***

Can be found in any location depending on pattern

Front 76

EM and Lupus Nephritis?

Back 76

Deposits in mesangium, subepithelial, or subendothelial

Front 77

Usual Presentation of Diabetic Nephropathy?

Back 77

Non-Nephrotic Proteinuria
Nephrotic Syndrome
CRF

Front 78

difference between renal involvement in Type 1 and Type 2 Diabetes?

Back 78

changes are the same

Front 79

Three Main Morphological Changes in Diabetic Nephropathy?

Back 79

Capillary BM Thickening
Diffuse Mesangial Sclerosis
Nodular Glomerulosclerosis (**kimmelsteil-Wilson nodules**)

Front 80

Diabetic Nephropathy and IF?

Back 80

Linear IgG Deposits (not anti-GBM?)
Nodules may also show IgG

Front 81

EM and Diabetic Nephropathy?

Back 81

BM Thickening
Diffuse Mesangial Expansion
NO IMMUNE COMPLEX DEPOSITS

Front 82

Most common renal amyloid?

Back 82

Light-Chain (AL)
or
AA type

Front 83

How do patients present with renal amyloidosis?

Back 83

Nephrotic Syndrome

Front 84

Kidney size in Amyloidosis?

Back 84

Normal or Enlarged b/c of deposits

Front 85

Morphology of Renal Amyloidosis?

Back 85

Hyaline substance deposits mainly in cap walls of glomeruli and blood vessels, mesangium, and interstitium

Later in progression may form nodules or obliterate glomerulus

Front 86

Special stain for amyloid?

Back 86

Congo Red w/ apple green birefringence

Front 87

IF for Renal Amyloidosis?

Back 87

Deposits of Light Chain
Lambda Light Chain > Kappa

Front 88

EM and Renal Amyloidosis?

Back 88

Randomly arranged fibrils, 10-12nm in diameter

Front 89

Who causes Chronic GN?

Back 89

All glomerulopathies can

Front 90

Morphology of Chronic GN?

Back 90

Small Kidneys w/ thin cortex
Diffuse, Global Glomerulosclerosis
Arterial and arteriolar sclerosis
Marked Tubular Atrophy
Interstitial Fibrosis
Lymphocytic Interstitial Infiltraiton

Front 91

Chronic GN and IF?

Back 91

Findings according to underlying disease

Front 92

Chronic GN and EM?

Back 92

findings according to underlying disease