Robbins - 517-533 - Glomerulus, Nephrotic, Nephritic Flashcards Preview

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Flashcards in Robbins - 517-533 - Glomerulus, Nephrotic, Nephritic Deck (154):
1

Glomerular diseases are often ___ mediated

Immunologically

2

___ injury may account for instances of GN in which either there are no deposits of Ab's or immune complexes

T Cell-Mediated injury

3

___ mechanisms underlie most types of primary glomerular diseases

Immune

4

___ molecules from adjancent foot processes bind to each other thru disulfide bridges

Nephrin

5

2 etiologies of Dense Deposit Disease

Auto-Ab to C3 Nephritic Factor - uncontrolled cleavage of C3; Mutations or Auto-Ab's to Factor H

6

2 most prevalent primary glomerular diseases in Adults

1. Focal Segmental Glomerulosclerosis; 2. Membranous Nephropathy

7

2 Typical Features of Immune Complex Disease

(1) Hypercomplementemia; (2) Granular deposits of IgG, complement on GBM

8

3 damaging substances released by Neutrophils

Proteases, ROS, AA metabolites

9

3 most frequent systemic causes of nephrOtic syn in adults are

Diabetes, Amyloidosis, SLE

10

5 manifestations of Nephritic Syndrome

Hyper GrAPE: HTN, Gross Hematuria, Azotemia, Proteinuria, Edema

11

85% of Membranous Nephropathy is caused by

Ab's that cross-react with podocyte antigens

12

AA metabolites released by Neutrophils cause

reduction in GFR

13

Ab-mediated GN in humans results from

Formation of auto-Ab's directed against GBM

14

Ab's against what are suspected when immune complexes are not found in GN

Against Glomerular cell antigens

15

Acute Postinfectious GN is caused by

Glomerular deposition of immune complexes; Results in proliferation and damage to glomerular cells and infiltration of leukocytes

16

After "maladaptive" changes following significant Nephron loss, what happens?

Capillary obliteration, Increased deposition of mesangial matrix and plasma proteins, and ultimately sclerosis of glomeruli --> Further reductions in nephron mass

17

After significant nephron loss, remaining glomeruli tend to undergo ___? This is associated with what hemodynamic changes?

Hypertrophy to maintain overall renal fxn; Increases single-nephron GFR, BF, and transcapillary pressure

18

Age range for IgA Nephropathy

Children and Young Adults

19

Age range for Minimal Change Disease

1-7 years

20

Age range of Membranous Nephropathy

30-60, slowly progressive

21

Alport Syndrome is a mutation in

Alpha chains of Type IV Collagen

22

Alport Syndrome is a type of

Hereditary Nephritis

23

Alport Syndrome is characterized by

Nephritis, Nerve Deafness, Eye disorders

24

Anti-GBM Ab GN is characterized by what IF pattern

Linear

25

Anti-GBM Ab-mediated Crescentic GN is characterized by

Linear deposits of Ig, and often C3 on GBM

26

Anti-GBM Crescentic: Clinical presentation

Severe glomerular damage with necrosis and crescents - Rapidly progressive GN

27

Antibodies directed to what glomerular region tend NOT to elicit inflammation

Subepithelial

28

Antigen in most cases of Membranoproliferative GN

Unknown

29

Antigens in Classic Crescentic GN

Fixed antigens in GBM

30

Auto-Ab to C3 Nephritic Factor - uncontrolled cleavage of C3; Mutations or Auto-Ab's to Factor H

2 etiologies of Dense Deposit Disease

31

Azotemia, Hematuria, HTN in NephrOtic syn

Little to no Azotemia, Hematuria, HTN

32

Basketweave =

Hereditary Nephritis

33

Best-characterized Anti-GBM GN

Classical Anti-GBM Crescentic GN

34

Causes of MPGN vs DDD

MPGN is immune complex deposition vs DDD is Complement dysregulation

35

Characteristic histological findings in RPGN

Crescents

36

Characteristic IF picture of IgA Nephropathy

Mesangial deposition of IgA (often with C3, properdin, and small amounts of IgG or IgM)

37

Chronic renal disease damages what components of nephron

All 4

38

Classic presentation of Acute Post-Strep GN

Nephritic Syndrome

39

Collapse of Glomerular Tuft and Podocyte Hyperplasia

Collapsing Gnephropathy is characterized by

40

Collapsing Gnephropathy is a variant of

FSGS

41

Collapsing Gnephropathy is characterized by

Collapse of Glomerular Tuft and Podocyte Hyperplasia

42

Complexes deposited in what location tend to elicit inflammatory reaction

Endothelium or subendothelium

43

Crescents can be a complication of any

immune complex nephritides

44

Cut-offs for Proteinuria and Hypoalbuminea in NephrOtic syndrome

3.5g proteinuria, 3 g/dL Albumin

45

DDD (as opposed to Type 1 MPGN) is characterized by

Ribbon-like intramembranous deposits

46

Deposition of Auto-Ab's directed against GBM show what pattern on IF

Linear pattern

47

Deposition of circulating immune compelxes gives what IF pattern

Granular

48

Diameter of Fenestra

70-100 nm

49

Diameter of Filtration Slits

20-30 nm

50

Early and Late EM changes in Hereditary nephritis

Early: Thin GBM; Late: Basketweave

51

Elevation of BUN and Creatinine; Usually reflects decreased GFR

Azotemia

52

EM findings in Post-infectious GN

Subepithelial Humps

53

Evidence suggests that IgA Nephropathy is an abnormality in

IgA production and clearance; Ab's against abnormally glycated IgA

54

FSGS is associated with what other conditions

HIV, Heroin abuse; Secondary event in other forms of GN

55

Fundamental Abnormality in Dense Deposit Disease

Excessive complement activation

56

Glomerular lesions from immune complex disease usually consist of

Leukocyte infiltration into glomeruli; Variable proliferation of endothelial, mesangial, and parietal epithelial cells

57

Gross Hematuria, Proteinuira, Azotemia, Edema, HTN: Hyper GrAPE

Nephritic Syndrome

58

Hallmark of IgA Nephropathy

Deposition of IgA in Mesangium

59

Hemodynamic changes caused by Hypertrophy of remaining nephrons in end-stage kidney disease lead to

Further endothelial and podocyte injury, increased glomerular permeability to proteins, accumulation of proteins and lipids in mesangial matrix

60

Hereditary Nephritis is caused by

Mutations in genes encoding GBM proteins

61

Histologic features of glomeruli in FSGS

Increased MM, Obliterated capillary lumina, Deposition of hyaline masses and lipid droplets

62

Histological features shared by Type 1 MPGN and DDD

Lobular G, Proliferation of Mesangial and Endothelial cells, Thickened GBM, Tram Track

63

How do immune complexes mainly produce injury in Glomerulus

Activation of complement and recruitment of leukocytes

64

How does Membranous Nephropathy contrast to Minimal Change disease

No selectivity of proteins, No response to corticosteroids

65

How does Thromin contribute to GN

Causes leukocyte infiltration and Glomular Cell proliferation by triggering PAR's (protease-activated receptors)

66

IF findings in Post-infectious GN

Granular deposits of IgG and Complement

67

IF showing deposition principally in mesangial regions

IgA Nephropathy

68

IgA Nephropathy is often considered a local variant of

Henoch-Schonlein Purpura

69

Inheritance of Hereditary Nephritis

Most commonly X-linked

70

Interestitial diseases are more likely caused by

Toxic or infectious agents

71

Irregular foci of thickening or attenuation with pronounced splitting and lamination of lamina densa

What is basketweave appearance

72

Kidney sin Anti-GBM Ab-mediated Crescentic GN

Enlarged and pale with Petechiae

73

LM of Glomeruli in Hereditary Nephritis

Normal until late in disease course

74

Lobular G, Proliferation of Mesangial and Endothelial cells, Thickened/Split GBM (tram track)

Histological features shared by Type 1 MPGN and DDD

75

Main histologic feature of Membranous Nephropathy

Diffuse thickening of capillary wall

76

Manifestation of Hereditary Nephritis

Hematuria and slowly progressing proteinuria and declining renal function

77

Manifestation of Minimal Change Disease

Insidious nephrotic syndrome in otherwise healthy child

78

Manifestation of Rapidly Progressive GN

ProMD: Proteinuria, Microscopic Hematuria, Dysmorphic RBCS, Casts

79

Manifestations of Nephrotic besides Proteinuria, Hypoalbumin, Edema

Hyperlipidemia, Lipiduria

80

Membranous Nephropathy is a form of

Chronic Immune Complex Glomerulonephritis

81

Membranous Nephropathy is characterized by

Subepithelial Ig deposits along GBM

82

Most cases of RPGN are ___ mediated

Immune

83

Most characteristic LM change in Post-infectous GN is

Increased cellularity of tufts in nearly all glomeruli

84

Most common cause of Nephritic Syndrome worldwide

IgA Nephropathy

85

Most common glomerular disease revealed by renal bx worldwide

IgA Nephropathy

86

Most important of the primary glomerular lesions that characteristically lead to nephrotic syndrome

Focal and Segmental Glomerulosclerosis (Adults); Minimal Change Disease (Children)

87

Most planted antigens induce what pattern in IF microscopy

Granular pattern

88

Nephritic syndrome lesions are characterized by

Proliferative changes and Leukocyte infiltration

89

Nephrolithiasis is manifested by

Renal colic, hematuria, Recurrent stones

90

Normal appearance by LM, but diffuse effacement of foot process by EM

Minimal Change Disease

91

Oliguria or Anuria + Recent Onset Azotemia

Acute Kidney Injury

92

Once in end-stage renal disease, kidneys show widespread

Glomerusclerosis

93

Only visible glomerular abnormality in Minimal Change Disease

Uniform and difuse effacement of foot processes of podocytes

94

Onset of IgA Nephropathy

Episode of gross hematuria that occurs within 1-2 days of nonspecific URI

95

Onset of Post-infectious GN

Abrupt

96

Pattern of deposits on IF in Membranous Nephropathy

Granular

97

Podocytes in EM of FSGS

Effacement of Foot Processes

98

Postrenal Azotemia

When urine flow is obstructed below level of kidney

99

Prerenal Azotemia

Hypoperfusion of Kidneys; Decreases GFR in absence of parenchymal damage

100

Presentation/Age of Hereditary Nephritis

Hematuria/Proteinuria at 5-20 years; Renal failure at 20-50 years

101

Primary FSGS accounts for what percent of nephrOtic syn

20-30%

102

Probably cause of HTN in Nephritic syn

Fluid Retention and Increased Renin

103

Prognosis of Acute Post-Infectious GN in children vs adults

Most children recover; worse in adults

104

Prognosis of DDD

Poor, worse than Type 1 MPGN

105

Prognosis of FSGS

Poor, 50% develop end-stage kidney disease in 10 years

106

Prognosis of Minimal Change Disease

Good, more than 90% of children respond to short course corticosteroids

107

Prognosis of Type 1 MPGN

Poor

108

Progression of FSGS leads to what histological picture

Global Sclerosis, Pronounced Tubular Atrophy, Interstitial Fibrosis

109

Proteinuria, Microscopic Hematuria, Dysmorphic RBCS, Casts

Manifestation of Rapidly Progressive GN

110

Puzzling aspect of Membranous Nephropathy

Immune complexes cause capillary damage in absence of inflammatory cells (likely via complement instead)

111

RAAS in Nephrotic Syndrome

Activated due to decreased intravascular volume

112

Renal colic, hematuria, Recurrent stones

Nephrolithiasis is manifested by

113

Renal function in Minimal Change Disease

preserved in most children

114

RPGN is characterized by

Progressive loss of renal function, Lab findings of Nephritic Syndrome, often severe oliguria

115

Segmental distribution of necrotizing and crescentic GN is typical of

ANCA-associated crescentic GN

116

Spike and Dome =

Membranous Nephropathy

117

Subepithelial Humps =

Post-infectious GN

118

The classic case of poststrep GN develops in

a child 1-4 weeks after GAS infection

119

The major component of slit diaphragms

Nephrin

120

Timeline of Rapidly Progressive Glomerulonephritis

Fews days or weeks

121

Tissue injury in Post-Strep GN is primarily caused by

complement activation by the classical pathway

122

Tram Track =

MPGN

123

Tubular diseases are more likely caused by

Toxic or infectious agents

124

Two possible causes of Membranoproliferative GN

Circulating immune complexes, or planted antigen the in situ complex formation

125

Tx of Anti-GBM Ab-mediated Crescentic GN

Plasmapharesis

126

Tx of Minimal Change Disease

Corticosteroids

127

Type 1 MPGN (as opposed to DDD) is characterized by

Discrete subendothelial electron-dense deposits

128

Type of Collagen in GBM

Type IV

129

Types of "planted" antigens

Nucleosomal complexes, Bacterial products, Large aggregated proteins, Immune complexes

130

Uremia

When Azotemia gives rise to clinical manifestations and systemic biochemical abnormalities

131

Urine in Post-Infectious GN

Gross Hematuria (smoky brown), Some proteinuria

132

Visceral Epithelial Cells =

Podocytes

133

Well-develped Membranous Nephrophy shows

Diffuse thickening of capillary wall

134

What can reverse podocyte changes in Minimal Change Disease

Corticosteroids

135

What causes 65% of primary glomerual disease in children?

Minimal Change Disease

136

What causes the "splitting of the GBM" (tram track)?

Extension of processes of mesangial and inflammatory cells into peripheral capillary loops and deposition of mesangial matrix

137

What conformational change appears to be key to auto-Ab attack of GBM

Alpha3 subtupe of Type IV collagen

138

What does Azotemia usually reflect

Decreased GFR

139

What endogenous podocyte antigen is most recognized by causative Auto-Ab's in Membranous Nephropathy?

PLA2 receptor

140

What forms crescents in RPGN

Proliferation of Parietal Cells and Migration of Monocytes/Macrophages in Bowman's space

141

What is Azotemia?

Elevation of BUN and Creatinine; Usually reflects decreased GFR

142

What is basketweave appearance

Irregular foci of thickening or attenuation with pronounced splitting and lamination of lamina densa

143

What is more pronounced in RPGN than in Nephritic Syndrome

Oliguria and Azotemia

144

What is the Tram Track

Thickened GBM with double contour glomerular capillary wall in MPGN

145

What is thought to cause injury in neutrophil-independent GN

Complement, MAC

146

What is thought to represent initiating event in FSGS?

Injury to podocytes

147

What likely damages mesangial cells and podocytes in Membranous Nephropathy

MAC activated by Immune Complexes

148

What mutation seems to be strongly associated with increased risk of FSGS and renal fialure in AA's

APOL1

149

What percent of GFR is reduced before inexorable progression to end-stage kidney disease

30-50%

150

What predicts progression and response to intervention in IgA Nephropathy?

Bx

151

When anti-GBM Ab's cross react with BM of lungs

Goodpasture Syndrome

152

When Azotemia gives rise to clinical manifestations and systemic biochemical abnormalities

Uremia

153

Which are permeable in glomerulus: cations or anions?

Cations - More cationic, more permeable

154

Which RPGN subtype shows segmental necrosis?

All 3