Glomerular Dx Flashcards

1
Q

Do we know a lot about the etiologic factors involved in primary glomerulonephritis

A

No

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2
Q

What are the different forms of antibody mediated glomerular injury

A

In situ immune complex deposition in the glomerulus

Circulating immune complex deposition

Antibody to glomerular cells

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3
Q

Two forms of antibody mediated glomerular injury

A

Antibody reaction with intrinsic glomerular antigens

Antibody reaction with extrinsic antigens in the glomerulus from the circulation

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4
Q

Two forms of antibody reaction with intrinsic glomerular antigens

A

Masugi/ nephrotoxic nephritis

Heymann nephritis

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5
Q

What is masugi nephritis

A

Antibody reaction against intrinsic fixed normal glomerular basement membrane antigen

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6
Q

In which condition do you see anti-glomerular basement membrane glomerulonephritis which is human counterpart of masugi nephritis

A

Goodpasture syndrome

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7
Q

What is heymann nephritis

A

Antibody reaction against antigen complex (megalin) located on basal surface of visceral epithelial cell

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8
Q

What human condition resembles heymnn nephritis

A

Human membranous glomerulonephritis with an antigen that is the homologue of Megalin called m-type phospholipase A2 receptor

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9
Q

What is antibody reaction with extrinsic antigens in the glomerulus from the circulation

A

Antibodies reacts with previously planted non-glomerular antigens which interact with various intrinsic component of the glomerulus

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10
Q

What type of planted antigens can you find in antibody reaction with extrinsic antigens in the glomerulus from circulation

A
Bacteria
virus
 parasites products 
drugs 
large aggregate proteins like immunoglobulins ,DNA,  
 immune complexes
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11
Q

What do you see in immunofluorescence microscopy of antibody reaction with planted antigens in the glomerulus

A

Granular or heterogeneous pattern of immunoglobin deposition on mesangium, capillary wall or both

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12
Q

How is there disease in circulating immune complex deposition in glomerulus

A

Trapping of circulating antigens antibodies complexes in glomeruli due to physical chemical properties of complexes and hemodynamics

leads to complement activation leading to injury

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13
Q

 in circulating immune complex deposition What do you see in the immunofluorescence microscopy

A

Granular deposits along the glomerular basal membrane , the mesangium , rarely in subepithelium

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14
Q

How do antibodies to glomerular sells cause injury to glomerulus

A

Antibodies to mesangeal cells leads to cytolysis with mesangeal cell proliferation

Antibodies to endothelial cells cause damage and capillary thrombosis

Antibodies to epithelial cell glycoproteins result in polyanion loss and proteinuria

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15
Q

What immune cell is involved in cell mediated glomerular injury

A

T cells

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16
Q

Is it possible to have alternative complement activation in certain types of human glomerulonephritis

A

Yes

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17
Q

How can glomerular Cells participate in their injury

A

Stimulate some cytokines like TGF beta , FGF , which stimulates production of extracellular matrix leading to development of glomerulosclerosis

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18
Q

C What are the factors affecting glomerular localization

A

Molecular charge
molecular size shape and deformability
glomerular hemodynamics
Mesangeal function

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19
Q

What makes the outer membrane and glomerular basement membrane negatively charged

A

Heparan sulfate

Sialoglycoprotein podocalyxin

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20
Q

How does the negative charge play a role in glomerulus localisation

A

Attracts cations macromolecules
Repel negative onions
Neutral charge molecule stay in mesangium

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21
Q

How are large complex cleared by the glomerulus

A

Through the mononuclear phagocyte system

22
Q

What mediates size dependent filtration

A

Type 4 collagen in the basement basement membrane and slits pores between podocytes

23
Q

Where do intermediate size molecules go in glomerulus

A

Sub endothelial

24
Q

Where do small size molecules go in glomerular

A

Intramembranous

Sub epithelium

25
Q

Function of mesangeal sells

A

Phagocytosis in basement membrane

26
Q

What system mediators can cause damage to the basement membrane of the glomerulus

A
Complement activation
Activation of coagulation system 
Leucocytic infiltration 
reactive oxygen species
 nephritic factors
27
Q

How does complement activation codes glomer basement membrane injury

A

Cell lysis
stimulation of mesangeal cell to produce oxidants, proteases, cytokines, Eicosanoids, nitric oxide and growth factors

28
Q

How does activation of coagulation system cause injury of basement membrane in glomerulus

A

Fibrin deposition in lumen in capillary walls which escape into Bowman space promoting proliferation of parietal epithelial cells which entraps platelets that degranulate them leading to free vasoactive peptide

29
Q

Are all the mediator of injury involved in every case

A

No

30
Q

When can you say that there is progression to chronic renal failure

A

When there’s destruction of enough functioning nephrons which reduces glomerular filtration rate to 50% or less than normal

31
Q

How do glomeruli survive renal failure at first

A

Compensatory hypertrophy
Increased single nephron GFR and GBF
Capillary hypertension

32
Q

What are the consequences of endothelial damage occurring in renal failure

A

Increased capillary permeability to proteins
Protein and fibrin deposition -> glomerular sclerosis
Less functioning nephrons
Viscous cycle of glomerulosclerosis

33
Q

Why is there tubule interstitial damage in renal failure

A

Sclerotic glomeruli -> ischemia of tubules downstream
Acute and chronic inflammation in interstitum
Damage / loss of peritubular capillary blood supply
Direct injury to tubularccells
Activation of tubular cells -> release of adhesion molecules , pro inflammatory cytokines , chemokines , GF

34
Q

What are the different histologic patterns seen in glomerular injur y

A

Hypercellularity
Thickening of GBM
Hyalinization and sclerosis

35
Q

Causes of hypercellularity in glomerular injury

A

Mesangeal cell proliferation
Leucocyte infiltration (neutrophils , mononuclear cells )
Parietal epithelial cells lining bowman’s space proliferation ->crescent shape mass of cells in urinary space which compresses glomerular tuft

36
Q

How do you see on light microscopy thickening of GBM

A

By seeing thickening of capillary walls

37
Q

How do you see thickening of GBM under electron microscope

A

Large hump shaped deficits under visceral epithelium

Smaller deposits on the basement membrane, Subendothelial or in the mesangi

Thickening of the basement membrane proper

Swelling of damaged endothelial or epithelial cells

Mesengeal interposition

38
Q

What is Hyalinization and sclerosis

A

Accumulation of homogeneous , eosinophilia material in glomerulus with obliteration of glomerular structural detail

39
Q

What do you under electron microscopy in case of Hyalinization and sclerosis

A

Extracellular material deposit made up of plasma protein and GBM material , mesangeal matrix

40
Q

Diffuse lesion in glomerulus

A

Involves all glomeruli

41
Q

Focal lesion of glomerulus

A

Some glomuleri affected

42
Q

Global injury to glomerulus

A

Whole glomerulus affected

43
Q

Segmental injury

A

Parts of glomerulus affected

44
Q

Mesangeal injury

A

Mainly mesangeal portion of glomerulus

45
Q

Proliferative changes in the glomerulus

A

Hyper cellularity of glomerulus with proliferation of indigenous cells and recruitment of leukocytes following complement activation

46
Q

What is membranous change in glomerulus

A

Thickening of peripheral capillary loops due to basement membrane expansion

47
Q

What are membranous proliferative changes in the glomerulus

A

Combination of hyper cellularity and basement membrane thickening

48
Q

What are crescentic changes in glomerulus

A

Florid proliferation of Pareto cells lining the Bowmans capsule and macrophages which can compress the glomerulus

49
Q

Manifestation of glomerular disease

A
Asymptomatic proteinuria 
nephrotic syndrome 
hematuria 
nephritic syndrome
 rapidly progressive glomerulonephritis 
chronic renal failure
50
Q

Why is there a proteinuria in glomerular injury

A

Increased permeability to protein in glomerulus