Robbins - 517-533 - Glomerulus, Nephrotic, Nephritic Flashcards
(154 cards)
1
Q
Glomerular diseases are often ___ mediated
A
Immunologically
2
Q
___ injury may account for instances of GN in which either there are no deposits of Ab’s or immune complexes
A
T Cell-Mediated injury
3
Q
___ mechanisms underlie most types of primary glomerular diseases
A
Immune
4
Q
___ molecules from adjancent foot processes bind to each other thru disulfide bridges
A
Nephrin
5
Q
2 etiologies of Dense Deposit Disease
A
Auto-Ab to C3 Nephritic Factor - uncontrolled cleavage of C3; Mutations or Auto-Ab’s to Factor H
6
Q
2 most prevalent primary glomerular diseases in Adults
A
- Focal Segmental Glomerulosclerosis; 2. Membranous Nephropathy
7
Q
2 Typical Features of Immune Complex Disease
A
(1) Hypercomplementemia; (2) Granular deposits of IgG, complement on GBM
8
Q
3 damaging substances released by Neutrophils
A
Proteases, ROS, AA metabolites
9
Q
3 most frequent systemic causes of nephrOtic syn in adults are
A
Diabetes, Amyloidosis, SLE
10
Q
5 manifestations of Nephritic Syndrome
A
Hyper GrAPE: HTN, Gross Hematuria, Azotemia, Proteinuria, Edema
11
Q
85% of Membranous Nephropathy is caused by
A
Ab’s that cross-react with podocyte antigens
12
Q
AA metabolites released by Neutrophils cause
A
reduction in GFR
13
Q
Ab-mediated GN in humans results from
A
Formation of auto-Ab’s directed against GBM
14
Q
Ab’s against what are suspected when immune complexes are not found in GN
A
Against Glomerular cell antigens
15
Q
Acute Postinfectious GN is caused by
A
Glomerular deposition of immune complexes; Results in proliferation and damage to glomerular cells and infiltration of leukocytes
16
Q
After “maladaptive” changes following significant Nephron loss, what happens?
A
Capillary obliteration, Increased deposition of mesangial matrix and plasma proteins, and ultimately sclerosis of glomeruli –> Further reductions in nephron mass
17
Q
After significant nephron loss, remaining glomeruli tend to undergo ___? This is associated with what hemodynamic changes?
A
Hypertrophy to maintain overall renal fxn; Increases single-nephron GFR, BF, and transcapillary pressure
18
Q
Age range for IgA Nephropathy
A
Children and Young Adults
19
Q
Age range for Minimal Change Disease
A
1-7 years
20
Q
Age range of Membranous Nephropathy
A
30-60, slowly progressive
21
Q
Alport Syndrome is a mutation in
A
Alpha chains of Type IV Collagen
22
Q
Alport Syndrome is a type of
A
Hereditary Nephritis
23
Q
Alport Syndrome is characterized by
A
Nephritis, Nerve Deafness, Eye disorders
24
Q
Anti-GBM Ab GN is characterized by what IF pattern
A
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
