Nephrotic Syndrome

Question 1

define Nephrotic syndrome

Criteria need 3/4

Answer 1

lose over 3.5 g protein per day cannot be compensated by hepatic albumin synthesis –> decr plasma osmotic pressure –> edema

1) albuminuria
2) hypoalbuminemia
3) edema
4) hyperlipidemia

Question 2

Nephrotic syndrome due to …

Answer 2

incr permeability of glomerular capillary wall to plasma proteins

Question 3

incr permeability of capillary wall in Nephrotic syndrome due to either …

Answer 3

1) structural damage = decr size selectivity

2) loss of neg charge = decr charge selectivity

Question 4

causes of nephrotic syndrome include…

Answer 4

1) chronic glomerular disease

2) sclerosing glomerular disease

Question 5

major oncotic protein lost thru urine excretion is…

Answer 5

albumin and uncompensated by incr hepatic albumin synthesis

Question 6

what is effect of hypoalbuminmia

Answer 6

1) decr oncotic pressure
2) shift of fluid to extravascular space
3) edema
4) decr effective vascular volume –> Na+/H2O retention

Question 7

coupled to incr albumin synthesis is …

Answer 7

1) incr hepatic synthesis of LDL

2) hyperlipidemia or lipiduria

Question 8

clinical presentation of nephrotic syndrome (7)

Answer 8

1) edema
2) low serum albumin
3) 4+ proteinuria >3.5 g protein lost per hour
4) hyperlipidemia
5) lipiduria
6) malnourish in kids
7) lethargy

Question 9

complications of nephrotic syndrome

1) AT3
2) HDL
3) immunoglobulin/complement (factor B)
4) decr albumin
5) hypercholesterolemia
6) Na+/k+
7) vitamin d

Answer 9

1) incr coag factors, decr AT3, thromboembolic, renal VEIN thrombosis
2) accel atherogenesis
3) susceptibility to infection from encapsulated
4) edema, hypotension,
5) accelerated atheorgenesis
6) low Na, low K
7) decr vitamin d

Question 10

Non-inflamm causes of glomerular injury

Answer 10

circulating factors or Ig’s bind to GEC membranes or GBM without fixing complement –> lose charge selectivity first

Question 11

Inflamm causes of glomerular injury

Answer 11

1) complement fixing GEC Ab’s = alternative pathway
2) MAC incr permeability of GBM (lose size selectivity first)

–> membranous nephropathy

Question 12

Classic mechanism of edema formation in nephrotic

Answer 12

1) proteinuria
2) decr serum albumin
3) decr oncotic pressure
4) volume depletion
5) incr ADH/aldosterone
6) edema/Na+ retention

Question 13

More common mechanism (not classic) for edema in nephrotic syndrome

Answer 13

1) primary defect in Na+ excretion at collecting duct or

low serum albumin

2) edema (Na+ retention)
NO VOLUME DEPLETION JUST VOLUME EXPANSION
DECR ALDOSTERONE

Question 14

what does maltese cross indicate

Answer 14

lipid vacuoles free or in casts under polarized light

Question 15

biopsy everyone with nephrotic syndrome unless

2

Answer 15

1) diabetic

2) treat child first for minimal change disease

Question 16

if you see scarring in glomerulus, indicates …

if you see thicker membranes in glomerulus, indicates …

if you see hypercellularity in glomerulus, indicates…

Answer 16

1) focal sclerosis
2) membranous
3) proliferative

Question 17

linear immunofluorescence indicates..

Answer 17

goodpasture’s

Question 18

EM patterns include…

Answer 18

1) podocyte foot process fusion
2) subendo deposits = inner side of capillary wall
3) subepithelial (membranous deposits) = outside basement membrane

Question 19

Hereditary nephrotic syndrome

1) etiology
2) similar to …
3) signs…
4) treatment …

Answer 19

1) mutation of slit diaphragm proteins - nephrin or podocin
2) minimal change or FSGS
3) ascites, edema, failure to thrive
4) resistant to steroids; transplant at 2 y/o

Question 20

minimal change disease

1) presenting age
2) signs and symptoms
3) lab and urinalysis
4) assoc with …
5) due to?
6) treatment

Answer 20

1) 2-6 y/o
2) edema/ascites, HTN
3) normal or slight decr renal fxn
4+ protein, hyaline casts, microscopic hematuria RARE

4) allergy/atopy
Hodgkin’s lymphoma
NZSAIDS

5) T cell disorder

6) corticosteroids (prednisone)
or short course oral cytoxan for relapsers

Question 21

Minimal change disease

1) on light microscopy
2) on EM
3) on IF

Answer 21

1) normal
2) negative
3) foot process fusion

Question 22

effect of steroid therapy on urine protein in minimal change disease

Answer 22

patients respond very quickly to steroids but often relapses so need recurrent

or give oral cytoxan/cyclophosphamide

Question 23

pathogenesis of minimal change disease

Answer 23

1) circulating factor
2) podocyte injury (fusion or alter charge density)
3) proteinuria

Question 24

T cell hypothesis of minimal change

Answer 24

1) podocyte is epith cell but can become antigen presenting cell
2) podocyte turn on CD80 and secrete which can interact with CD4 T cell to release lymphokines and damage podocytes

Question 25

FSGS

light microscopy

Answer 25

1) glomeruli normal appearing with focal segmental scarring

in some glomeruli and within glomerulus

Question 26

FSGS

1) age population/race
2) lab and urinalysis
3) assoc
4) pathophys
5) treatment
6) prognosis

Answer 26

1) 20-40 y/o
african american

2) renal function normal or slight decr
UA = 4+ protein, hyaline casts, MICROSCOPIC HEMATURIA COMMON

3) idiopathic or with HIV

4) circulating factor = suPAR
viral factor = HIV infection of podocyte
African american = APOL1

5) corticosteroids (pred) x 6 mo
calcineurin inhib (cyclosporin)

6) progress to dialysis but poor

Question 27

etiology of focal sclerosis

Answer 27

1) idiopathic
2) IV heroin
3) HIV
4) sickle cell, obesity

Question 28

Effect of suPAR in fSGS

Answer 28

1) suPAR expressed in podocytes
2) acftiv glomeruli and affect podocyte binding to basement membrane
3) proteinuria

Question 29

APOL1 role in FSGS

Answer 29

tradeoff between APOL1 protective against sleeping sickness but leads to FSGS

Question 30

HIV nephropathy
1) ___ syndrome

2) signs on microscopy
3) common populations
4) treatment

Answer 30

1) nephrotic
2) collapsing focal and segmental GN, reticuloendothelial inclusions, tubular dilation microcysts DUE TO VIRUS NOT HIV
3) 80% black, 50% IVDA, before AIDS
4) anti-retroviral

Question 31

membrane nephropathy
1) etiology
primary vs. secondary

2) presents with ___ syndrome
3) progress to ___ if untreat
4) age

Answer 31

1) primary = idiopathic 2/3 due to antibody against phsopholipase A2 on podocyte

secondary = hep B, gold, mercury, SLE, cancer

2) nephrotic
3) CKD
4) 40-50 y/o

Question 32

mechanism of injury in membrane neuropathy

Answer 32

1) antibody bind phsopholipase A2 on podocyte foot processes
2) damage podocyte directly
3) proteinuria

Question 33

Screening for membranous nephropathy and carcinomas

Answer 33

1) H&P

2) CBC
3) CXR, mammogram
4) stool test for occult blood, sigmoidoscopy

Question 34

HIV assoc membranous GN
1) found in …

2) presents with
3) responds to..

Answer 34

1) chronic HBsAg carrier
children

2) nephrotic syndrome
3) interferon

Question 35

MPGN
1) presentation with ___ syndrome

2) lab tests
3) signs on microscopy
4) type 1 vs. type 2

Answer 35

1) nephrotic syndrome
mildly decr renal function
HTN

2) HCV positive, low serum complement
3) hypercellularity + GBM thickening,

4) type 1 = HCV, idiopathic, SLE
type 2 = primary complement, post strep GN

Question 36

Distinguish btwn type 1 and type 2 MPGN

Answer 36

both = mesangial prolif and GBM thickening

type 1 = granular IgG
subendo deposit

type 2 = dense intramembranous deposit

Question 37

how to test for type 1 vs. type 2

Answer 37

measure serum complement
type 1 = low C3 and C4
type 2 = low C3 but normal C4

Question 38

HCV assoc MPGN type 1

1) found in …
2) labs
3) nephrotic or not
4) treatment
5) skin findings

Answer 38

1) adults with HCV
2) HTN
elev creatinine
low C3 and C4, 70% elev LFT

3) nephrotic or nonnephrotic proteinuria
4) inteferon
5) palpable purpura

Question 39

palpable purpura indicates what GN

Answer 39

HCV assoc MPGN type 1