Nephrotic Syndrome Flashcards
define Nephrotic syndrome
Criteria need 3/4
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
Nephrotic syndrome due to …
incr permeability of glomerular capillary wall to plasma proteins
incr permeability of capillary wall in Nephrotic syndrome due to either …
1) structural damage = decr size selectivity
2) loss of neg charge = decr charge selectivity
causes of nephrotic syndrome include…
1) chronic glomerular disease
2) sclerosing glomerular disease
major oncotic protein lost thru urine excretion is…
albumin and uncompensated by incr hepatic albumin synthesis
what is effect of hypoalbuminmia
1) decr oncotic pressure
2) shift of fluid to extravascular space
3) edema
4) decr effective vascular volume –> Na+/H2O retention
coupled to incr albumin synthesis is …
1) incr hepatic synthesis of LDL
2) hyperlipidemia or lipiduria
clinical presentation of nephrotic syndrome (7)
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
complications of nephrotic syndrome
1) AT3
2) HDL
3) immunoglobulin/complement (factor B)
4) decr albumin
5) hypercholesterolemia
6) Na+/k+
7) vitamin d
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
Non-inflamm causes of glomerular injury
circulating factors or Ig’s bind to GEC membranes or GBM without fixing complement –> lose charge selectivity first
Inflamm causes of glomerular injury
1) complement fixing GEC Ab’s = alternative pathway
2) MAC incr permeability of GBM (lose size selectivity first)
–> membranous nephropathy
Classic mechanism of edema formation in nephrotic
1) proteinuria
2) decr serum albumin
3) decr oncotic pressure
4) volume depletion
5) incr ADH/aldosterone
6) edema/Na+ retention
More common mechanism (not classic) for edema in nephrotic syndrome
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
what does maltese cross indicate
lipid vacuoles free or in casts under polarized light
biopsy everyone with nephrotic syndrome unless
2
1) diabetic
2) treat child first for minimal change disease
if you see scarring in glomerulus, indicates …
if you see thicker membranes in glomerulus, indicates …
if you see hypercellularity in glomerulus, indicates…
1) focal sclerosis
2) membranous
3) proliferative
linear immunofluorescence indicates..
goodpasture’s
EM patterns include…
1) podocyte foot process fusion
2) subendo deposits = inner side of capillary wall
3) subepithelial (membranous deposits) = outside basement membrane
Hereditary nephrotic syndrome
1) etiology
2) similar to …
3) signs…
4) treatment …
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
minimal change disease
1) presenting age
2) signs and symptoms
3) lab and urinalysis
4) assoc with …
5) due to?
6) treatment
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
Minimal change disease
1) on light microscopy
2) on EM
3) on IF
1) normal
2) negative
3) foot process fusion
effect of steroid therapy on urine protein in minimal change disease
patients respond very quickly to steroids but often relapses so need recurrent
or give oral cytoxan/cyclophosphamide
pathogenesis of minimal change disease
1) circulating factor
2) podocyte injury (fusion or alter charge density)
3) proteinuria
T cell hypothesis of minimal change
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
FSGS
light microscopy
1) glomeruli normal appearing with focal segmental scarring
in some glomeruli and within glomerulus
FSGS
1) age population/race
2) lab and urinalysis
3) assoc
4) pathophys
5) treatment
6) prognosis
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
etiology of focal sclerosis
1) idiopathic
2) IV heroin
3) HIV
4) sickle cell, obesity
Effect of suPAR in fSGS
1) suPAR expressed in podocytes
2) acftiv glomeruli and affect podocyte binding to basement membrane
3) proteinuria
APOL1 role in FSGS
tradeoff between APOL1 protective against sleeping sickness but leads to FSGS
HIV nephropathy
1) ___ syndrome
2) signs on microscopy
3) common populations
4) treatment
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
membrane nephropathy
1) etiology
primary vs. secondary
2) presents with ___ syndrome
3) progress to ___ if untreat
4) age
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
mechanism of injury in membrane neuropathy
1) antibody bind phsopholipase A2 on podocyte foot processes
2) damage podocyte directly
3) proteinuria
Screening for membranous nephropathy and carcinomas
1) H&P
2) CBC
3) CXR, mammogram
4) stool test for occult blood, sigmoidoscopy
HIV assoc membranous GN
1) found in …
2) presents with
3) responds to..
1) chronic HBsAg carrier
children
2) nephrotic syndrome
3) interferon
MPGN
1) presentation with ___ syndrome
2) lab tests
3) signs on microscopy
4) type 1 vs. type 2
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
Distinguish btwn type 1 and type 2 MPGN
both = mesangial prolif and GBM thickening
type 1 = granular IgG
subendo deposit
type 2 = dense intramembranous deposit
how to test for type 1 vs. type 2
measure serum complement
type 1 = low C3 and C4
type 2 = low C3 but normal C4
HCV assoc MPGN type 1
1) found in …
2) labs
3) nephrotic or not
4) treatment
5) skin findings
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
palpable purpura indicates what GN
HCV assoc MPGN type 1
