Nephrotic syndrome 12/21 Flashcards
(117 cards)
1
Q
pathoma. how is characterized neohrotic?
A
proteinuria > 3,5 g/d
2
Q
pathoma. 4 points about nephrotic
A
- Hypoalbuminemia –> pitting edema
- Hypogammaglobulinemia -> infection risk
- hypercoagulable state -> loss of ATIII.
- hyperlipidemia and hypercholesterolemia - may result in fatty casts in urine
3
Q
Hypoalbuminemia –>
A
Hypoalbuminemia –> pitting edema
4
Q
Hypogammaglobulinemia ->
A
Hypogammaglobulinemia -> infection risk
5
Q
hypercoagulable state ->
A
Hypercoagulable state -> loss of ATIII, protein C and S.
Also, increased synthesis of fibrinogen
6
Q
Hyperlipidemia and hypercholesterolemia –>
A
hyperlipidemia and hypercholesterolemia - may result in fatty casts in urine
7
Q
Minimal change diseases - causes?
A
usually idopathic;
may be assoc. with hodgkin lymphoma
8
Q
LM - normal glomeruli; IF - negative, EM - effacement of podocyte foot processes. What disease?
A
Minimal change disease.
9
Q
Most common cause of nephrotic syndrome in children?
A
Minimal change disease.
10
Q
minimal change disease - response to steroids?
why?
A
excellent
because damage is mediated by cytokines from T cells
10
Q
what proteinuria in minimal change disease?
A
Selective.
Loss of albimun, but not immunoglobulin
11
Q
LM - segmental sclerosis and hyalinosis, IF - negative (often), EM - effacement of podocyte foot processes. What disease?
A
Focal segmental glomerulosclerosis.
12
Q
Focal glomerular sclerosis causes? 1 and 2.
A
1 - Idiopatic.
2 - HIV, heroin abuse, sickle cell disease, obesity, interferon treatment, congenital malformations.
13
Q
What disease is associated with drugs (NSAIDs, penicillamine)?
A
Membranous nephropathy.
14
Q
LM - diffuse capillary and GBM thickening without hypercellularity, IF - granular, EM - ,,spike and dome” appearance of subepithelial deposits. What disease?
A
Membranous nephropathy.
15
Q
Which of nephoritc syndromes is mediated by immune complexes?
A
Membranous nephropathy and membranoproliferative GN.
16
Q
Most common syndrome in African Americans?
A
Focal segmental glomerulosclerosis.
17
Q
Membranous nephropathy causes? 1 and 2.
A
1 - Idiopathic. (In FA 1 is antibodies to phospholipase A2 receptors).
2 - Drugs (NSAIDs, penicillamine, gold), infections (HBV, HCV, syphilis), SLE, tumors.
18
Q
EM - ,,spike and dome” appearance of subepithelial deposits. What disease?
A
Membranous nephropathy.
19
Q
Diabetic glomerulonephropathy mechanism?
A
Hyperglycemia –> nonenzymatic glycosylation of the vascular basement membrane/ tissue proteins–> hyaline arteriosclerosis/mesangial expansion.
20
Q
What is Kimmelstiel-Wilson nodules? What disease?
A
Nodular sclerosis of mesangium in diabetic glomerulonephropathy.
21
Q
Why there is hyaline arteriosclerosis in diabetic glomerulonephropathy?
A
Nonenzymatic glycosylation of vascular basement membrane –> hyaline arteriosclerosis.
22
Q
Which arteriole is more affected by diabetic nephropathy? What effect on glomerul?
A
Efferent arteriole. It leads to high GF pressure –> hyperfiltration –> glomerular hypertrophy and glomerulosclerosis.
23
Q
What deposits are in IF of membranous nephropathy?
A
Granular.
24
What are disruptions of glomerular charge barrier?
1 - direct sclerosis of podocytes.
| 2 - systemic process damages podocytes, e.g. diabetes, SLE.
25
Why there is hypercoagulable state in nephrotic syndrome?
Due to loss of antithrombin III.
26
Why there is increased risk of infections in nephrotic syndrome?
Due to hypogammaglobulinemia.
27
What is proteinuria in nephrotic syndrome? ( g/day)
>3,5 g/day.
28
What is the difference in pathogenesis of nephritic and nephrotic syndromes?
Nephritic: neutrophil-mediated glomeruli injury.
Nephrotic: T-cell and cytokines damage podocytes to lose their negative charge.
29
What is the hallmark of neprotic syndrome?
Effacement of podocyte foot processes.
30
A child with lymphoma. What renal disease is most likely to appear?
Minimal change disease.
31
What disease can trigger recent infections, immunization or immune stimulus? What is it - primary or secondary reason?
Minimal change disease. Primary.
32
Which disease has excellent response to corticosteroids?
Minimal change disease.
33
What disease can provoke sicle cells disease and HIV?
Focal segmental glomerulosclerosis.
34
African american uses heroin. What renal disease most likely to appear?
Focal segmental glomerulosclerosis.
35
O patient is treated with interferon. What renal disease most likely to appear?
Focal segmental glomerulosclerosis.
36
In focal segmental glomerulosclerosis IF usually is negative, but sometimes positive. For what structures it would be positive?
May be positive for nonspecific focal deposits of IgM, C3, C1.
37
Which 2 diseases have poor response to corticosteroids?
Focal segmental glomerulosclerosis and primary membranous nephropathy.
38
What disease cause antibodies to phospholipase A2 receptors? Is it primary or secondary reason?
Membranous nephropathy. Primary.
39
Which two nephrotic syndrome disease may progress to CKD?
Focal segmental glomerulosclerosis and membranous nephropathy.
40
What changes are seen in GBM affected by hyperglycemia?
GBM thickening and increased permeability.
41
What changes of glomeruli is caused by hyperfiltration?
Glomerular hypertrophy and glomerular scarring (glomerulosclerosis)
42
How is stained nodular glomerularsclerosis (Kimmelstiel-Wilson)?
Eosinophilic.
43
LM - mesangial expansion, GMB thickening, nodular glomerulosclerosis. What disease?
Diabetic glomerulonephropathy.
44
What states leads to further progression o nephropathy in diabethic glomerulonephropathy?
Glomerular hypertrophy and glomerulosclerosis.
45
What is seen in LM when diabetic glomerulonephropathy?3
Mesangial expansion, GMB thickening, nodular glomerulosclerosis.
46
What causes mesangial expansion in diabetic nehpropathy?
nonenzymatic glycolysation of tissue proteins.
47
In what disease are seen lipids in PCT?
Minimal change disease.
48
hematuria in nephrotic?
ABSENT
49
what is response of liver in nephrotic syndrome?
loss of albumin -> liver responds by increasing albumin synthesis. (AS WELL AS LIPIDS --> HYPERLIPIDEMIA)
50
mechanism in nephrotic. scheme.
glomerular injury -> inc. glomerular permeability -> proteinuri -> hypoalbuminemia -> decr. oncotic pressure. It leads to 2:
1. hypovolemia --> incr. aldosterone and ADH -> na and water retention - edema (due to retention and hypoalbuminemia directly)
2. incr. liver protein and lipid synthesis -> hyperlipidemia
51
What type of hyperaldosteronism are in nephrotic?
secondary hyperaldosteornism
52
Why liver produce lipids?
liver produce lipoproteins.
also, liver catabolism is impaired due to decreased lipoprotein lipase and abnormal transport of ciculating lipid particles
53
factors that leads to hypercoagulability in nephrotic?
loss of ATIII, loss of protein C and S, increased synthesis of fibrinogen
54
charge of GBM?
negative
55
to what charge molecules membrane is impermeable, normally?
membrane - negative;
impermeable to proteins, that are also negative (ALBUMIN)
56
in what nephrotic syndrome is selective proteinuria?
ONLY IN MINIMAL CHANGE.
in others - nonselective
57
what morphologic changes leads to nonselective proteinuria?
podocyte damage and fusion -> nonselective proteinuria
58
what GRG and Cr in nephrotic?
normal.
damaged glomeruli continue to operate at normal filtration rate, therefore renal function remains unchanged while proteins are still released into the urine
59
nephrotic. loss of PLASMA proteins -->?
decr. plasma protein binding --> increase in free plasma drug concentration, but drug toxicity is usually not increased
60
nephrotic. loss of transport proteins --> ?? 2 examples.
loss of thyroglobulin transport protein 0> thyroxin deficiency
loss of vit.D binding protein --> vit. D deficiency
61
minimal change. glomeruli - normal, but what may be seen?
lipids in PCT cells.
62
minimal change. population?
children (2-3 y/os), but may be teenagers (was the case with 15y/o girl using NSAIDS)
63
minimal change. characteristic feature?
diffuse effacement and fusion of podocyte foot
64
minimal change. two groups of causes?
1. idiopathic
2. immune dysregulation
65
minimal change. why immune dysregulation?
due to immunologic reaction to: immunizations, upper resp. infection (eg viral upper resp. infection), atopic disorders (reaction to pollen, dust, stings), drugs (eg NSAIDS), malignancy (Hodgkin lymphoma)
66
minimal change. Immune dysregulation mechanism. What cells?
T cells dysfunction
67
minimal change. T cells dysfunction --> overproduction of what?
IL-13
68
minimal change. how is named Il-13 (its function?)
glomerular permeability factor --> affected glomerular capillary wall/direct damages to podocytes -> effacement and fusion of foot processes
69
minimal change. two main points in patho?
T-cell dysregulation -> IL13 production, which is glomerular permeability factor
70
minimal change. what clinical unexpected?
hypertension and hematuria
note: urine - frothy (due to proteins)
71
focal segmental. LM?
SEGMENTAL SCLEROSIS AND HYALINOSIS
72
focal segmental. EM?
diffuse podocyte foot processe effacement similar as seen in minimal change disease
73
focal segmental. IF?
negative. sometimes might be positive if immune deposits occur in sclerotic region (IgM, C3, C1) (NOT ALONG GBM)
74
If in focal segmental IF positive, where deposits?
in sclerotic region
75
in what 2 diseases sclerosis and hyalinosis are typical?
Diabetic nephropathy and focal segmental
76
Diabetic nephropathy and focal segmental. What is the difference in symtoms?
Diabetes - autonomic neuropathy with overflow incontinence (rare, typically in chronic poorly controlled DM)
Focal segemtal - NO lower urinary symptoms
77
severe obesity - what diseases?
focal segmental
78
Diabetic nephropathy and focal segmental. due to direct and indirect podocyte injury. What are the examples?
direct - cytotoxic drugs
indirect - glomerular hyperfiltration
79
focal segmental - population?
adults
80
in children what diseases?
minimal change
81
in adult hispanics and african americans?
focal segmental
82
in adult caucasians?
membranous nephropathy
83
membranous nephropathy. LM?
DIFFUSE thickening of the GBM WITHOUT an increase in glomerular cellularity (hypercellularity)
84
membranous nephropathy. EM?
Subepithelial deposits.
Irregural, IgG + C3 complexes.
Resembles Spikes and domes - when stained with silver stain
85
membranous nephropathy. IF?
Granular deposits (IgG +C3)
86
membranous nephropathy. 2 causes group?
1. primary: idiopathic - anti-phospholipase A2 receptor antibodies
2. secondary - infections, drugs, solid tumors, SLE
87
anti-phospholipase A2 receptor antibodies (Anti-PLA2R antibodies) binds what?
PLA2R - autoantigen in glomerular podocytes
88
where is PLA2R?
autoantigen in glomerular podocytes
89
which autoantigen is very specific for membranous nephropathy?
Anti-PLA2R antibodies - positive titer rule out other nephrotic syndromes. also, titers correlate with diseases activity
90
membranous nephropathy. what chronic infections?
HBV, HCV, syphilis
91
membranous nephropathy. what solid tumors?
eg. lung, breast, prostate, colon
92
membranous nephropathy. drugs?
NSAIDS, penicilamine, gold
93
membranous nephropathy. what autoimmune?
SLE
94
most common cause of end-stage renal disease in USA?
diabetic nephropathy
95
diabetic nephropathy DM1 vs DM2? onset
DM1 >5years takes to develop
DM2 - can bet at the time of diagnosis
96
diabetic nephropathy. typical patients?
middle age-elderly with long history of DM
97
diabetic nephropathy. What is thickened?
GBM
98
diabetic nephropathy. what is expanded?
mesangium - increased mesangial matrix deposition
99
diabetic nephropathy. Glomerusclerosis - what finding? name
Kimmelstiel-Wilson nodules
100
diabetic nephropathy. what indicated IRREVERSIBLE damage?
Kimmelstiel-Wilson nodules
101
diabetic nephropathy. mechanism of function decline>
Over time, expansion of the mesangium and KW nodules formation compress the glomerular capillaries --> loss of glomerular function
102
where are Kimmelstiel-Wilson nodules?
in mesangium
103
Kimmelstiel-Wilson nodules - how stain?
H and E - eosinophilic
PAS positive
Ovoid/spherical shaped
lammelated appearance
104
diabetic neohropaty. urinalysis?
No red or white cells.
105
diabetic neohropaty. type of proteinuria?
affected more eferent than afferent --> high filtration rate --> hyperfiltration injury leads to MICROALMUNINURIA --> eventually to nephrotic syndrome
106
what molecule is negatively charged in GBM?
Heparan sulfate
107
mechanism how is lost negative charge in DM?
progressive loss of negative charge due to heparanase expression by renal epithelial cells --> leakage of albumins and other plasma proteins.
108
what are earliest morphological changes in DM nephropathy?
GBM thickening and mesangium expansion
109
What is screened for renal damage in DM?
ALBUMINS - with albumin specific urine assay (regular dipstic has low sensitivity)
110
Earliest manifestation of DM nephropathy?
ALBUMINURIA
111
what reflects glycosuria?
poor glycemic control
112
Ketones levels?
transient phenomenom in DM
113
what are 3 stages of DM nephropathy?
Hyperfiltration, incipient DN, overt DN
114
DN. Hyperfiltration? (2)
Glomerular hypertrophy and INCREASED GFR (GRAFIKAS!!!!!!)
115
DN. Incipient DN? 3
Mesangial expansion, GBM thickening, arteriolar hyalinosis
Moderately increased albuminuria
hypertension
116
DN. Overt DN?4
Mesangial nodule (KW), tubulointerstitial fibsosis
overt proteinuria
Nephrotic syndrome
decr. GFR
