Patho 4=>Nephrotic Syndrome

causing nephrotic syndrome 1-primary glomerular conditions typically ....... 2-systemic conditions can affect glomerulus {secondarily}->most common are.........

1-1]Minimal change disease -MCD{mostly affects children} 2]Focal segmental glomerulosclerosis-FSGD 3]Membranous nephropathy 4]Membranoproliferative GNI (MPGN I) +dense deposit disease (DDD) 2-1]DM 2]Amyloidosis 3]SLE

proteinuria 1-non-selective 2-selective

1-FSGS /Membranous nephropathy 2-MCD

Stains to examine kidney tissue under LM

1-H&E 2-PAS->entrapped material in pink color {FSGS} {Membranous nephropathy} 3-congo red 4-silver ->stains BM in black color {MCD} {Membranous nephropathy} 5-masson trichrom

Membranous nephropathy 1-Experimental model->.......... 2-........progressive 3-presentation is mostly b/w........ 4-...........-mediated **5-Characterized by {characteristic LM feature but may not appear early in disease}->............ 6-85% of cases are......... 7-15% of cases are........ 8-IF->........... 9-.........of inflammatory cells 10-Typically nephrotic syndrome of........... 11-minority might present as.......... 12-Rule out 2ry first->......... 13-.......in minority 14-proteinuria is........ 15-Not responsive to....... 16-Generally indolent->...........

1-Heymann nephritis {rat disease} 2-Slowly 3-30 & 60 years old {adults} 4-Immune complex 5-subepithelial deposits on GBM {diffuse thickening of capillary wall} {PAS stain} {in LM /can seen in EM} ☞Spikes->very beautiful (silver stain) 6-1ry caused by autoantibodies against podocyte Ag {endogenous podocyte Ag, phospholipase A2 receptor->Ag is most often recognized by causative autoantibodies} 7-2ry 1]Infections->chronic hepatitis B /syphilis /schistosomiasis /malaria 2]Malignant tumor->carcinoma of lung ,colon /melanoma 3]SLE &other autoimmune conditions 4]Drugs->penicillamine /captopril /nonsteroidal anti-inflammatory agents 8-Capillary granular (+) mainly for IgG &C3 9-Absence 10-insidious onset 11-non-nephrotic proteinuria 12-treating underlying cause is effective 13-Mild HTN 14- non-selective 15-steroids 16-only 40% will show progressive chronic kidney disease within years-decades

Most common glomerulopathies that can recur after renal transplantation are

1-IgA nephropathy 2-FSGS 3-Membranous nephropathy 4-Membranoproliferative glomerulonephritis

1-Most Common cause of nephrotic syndrome in children 2-Most common cause of nephrotic syndrome in adults in USA (African {genetic association like polymorphism in apolipoprotein L1} + Hispanic)

1-Minimal-Change disease (MCD) 2-Focal Segmental Glomerulosclerosis {FSGS}

Membranoproliferative Glomerulonephritis I (MPGNI) .VS. Dense Deposit Disease (DDD) 1-LM 2-Typically->........... 3-Some............ 4-Previously 5-now->2 separate entities 6-pathogenesis 7-LM features 8-EM 9-IF 10-Both are........ 11-40% of MPGN I progress to....... 12-DDD is.........than MPGN I 13-Recurrence in renal transplants is more in.........

1-Proliferative pattern (like PSGN)(proliferation of different types of cells->endothelial ,mesangial cells , WBCs but neutrophils << PSGN ) + GBM thickening 2-Nephrotic syndrome {children & adults} 3-1]only hematuria /non-nephrotic proteinuria 2]combined nephrotic nephritic picture 4-MPGN I & II 5-MPGN I {80% more}& dense deposit disease 6-1]immune complexes, but unknown Ag 2]2ry MPGN I->Hepatitis B ,C {associated with many->diopathic cases} /SLE /Extrarenal infections ..........1]Less clear 2]Excessive complement activation {autoantibody against C3 convertase= C3 nephritic factor->it stabilizes C3 convertase activation of alternative pathway (by uncontrolled C3 cleavage)} 3]factor H mutations /autoantibodies against factor H->prevents alternative pathway->AutoAB against factor H will ⬆️ alternative pathway 4]Hypocomplementemia of C3-?->consumption of C3 &less production from liver 7-1]glomeruli are large 2]Accentuated lobular appearance 3]Proliferation of mesangial &endothelial cells +infiltrating leukocytes 4]GBM is thickened 5]glomerular capillary wall ->double contour, "tram track" appearance, especially evident with use of silver or periodic acid-Schiff (PAS) stains-?->splitting of GBM 8-Subendothelial &mesangial deposits ...........dense ribbon-like deposits replacing lamina densa of GBM->not C3 (unknown) 9-C3, IgG, C1q, & C4 -granular capillary + mesangial .......only C3-granular capillary + mesangial 10-bad 11- ESRD 12-worse 13-DDD >MPGN I

complications of syndrome

1-Vulnerability to infections (staphylococcal & pneumococcal )-?->loss of immunoglobulins 2-Thrombotic/Thromboembolic complications (including renal venous thrombosis)-?->part to loss of anticoagulants {antithrombin III}

MSD .VS. FSGS 1-main manifestation is......... 2-proteinuria is.......... 3-worse 4-HTN is more likely to occur 5-reduction in GFR is more likely to occur 6-chronic kidney disease 7-part of a continuum{part of same spectrum of disease} 8-EM

1-nephrotic syndrome 2-selective......non-selective 3-FSGS >>MCD 4-FSGS 5-FSGS 6-<5%...... much more common {50% will develop ESRD in 10 years} 7-MCD is milder than FSGS 8-diffuse effacement of foot processes.......effacement of foot processes

Nephrotic syndrom 1-.........syndrom 2-manifestations are...........

1-renal clinical 2-1]hyperlipidemia 2]lipiduria 3]severe proteinuria 4]hypoalbuminemia->severe generalized edema due to ⬇️ in oncotic P 5]Generalized edema mostly appear in periorbital area /appear with gravity in lower limbs

Focal segmental glomerulosclerosis (FSGS) 1-Focal......+segmental.......->sclerosis of glomeruli 2-affect......... 3-divided into......... 4-Injury to podocytes is thought to............ 5-EM->.......... 6-Segmental sclerosis on LM->......... 7-IF->........... 8-If advanced->............... 9-........in renal transplant in some patients who had FSGS may occur (sometimes within 24 hours of transplantation) 10-Collapsing Variant->..........

1-some but not all glomeruli......in affected glomeruli ,only portion of capillary tuft is affected 2-1]Children 2]adults{more} 3-1]1ry (idiopathic) 2]2ry ☞progressive change after focal GN (IgA nephropathy) ☞maladaptation to nephron loss of any cause {ablation /unilateral agenesis (in remaining kidney adaptation is abnormal which lead to FSGS ) /loss due to any glomerular, tubulointerstitial , vascular problem(HTN)} ☞HIV-associated nephropathy ☞association with 1)massive obesity {hemodynamic changes , injury in podocytes ,production of cytokines like TGF-BETA} 2)heroin addiction 3)sickle cell disease 3]inherited ☞rare slit diaphragm protein mutations like podocin 4-represent initiating event of 1ry FSGS 5-effacement of foot processes 6-Entrapment of plasma proteins &lipids in foci of injury (appear as hyaline masses in glomeruli)+ ⬆️ mesangial matrix in foci of injury + segmental obliteration of capillary loops 7-nonspecific entrapment of IgM &complement in affected segments {commonly seen in lesion} 8-global sclerosis/ tubular atrophy/ interstitial fibrosis 9-Recurrence of proteinuria &subsequent FSGS 10-1]idiopathic / due to HIV / other causes 2]bad prognosis

Minimal-Change disease (MCD) 1-LM->.......... 2-EM->.......... 3-IF findings are........... 4-Most common be/w ages of.........,but can develop at any age 5-Pathogenesis in human is.......... 6-association with......./....... 7-Prognosis->1].........in children 2]..........in adult 8-GBM is.........under 1]EM 2]LM 9-.........development of nephrotic syndrome 10-nephrotic syndrome occurring here is good->....../...... 11-Usually loss is confined to small proteins (chiefly albumin)=......... 12->90% of children respond to............ 13-Recurrent proteinuria may occur->may become.......... 14-<5% develop chronic kidney disease after 25 years->mostly due to......... 15-...........is Characteristic

1-☞Normal glomerular appearance ☞❌ glomerular changes ☞cells of PCT often are heavily laden with protein droplets &lipids->2ry event {name was lipoid nephrosis-?->cellular accumulation of lipids is 2ry event} 2-diffuse (all glomeruli) effacement of podocyte foot processes (flattened foot process) {❌ deposits } ☞podocytes show: 1]vacuolization {development of vacuoles inside of them} 2]microvillous formation 3]occasional focal detachments {detachment of foot processes} from GBM ☞**changes->reversible by steroids, proteinuria remit (most of time) 3- (-) 4-1-7 years 5-still unknown 6-1]atopy like eczema &allergic rhinitis 2]Hodgkin 7-1]Relatively good 2]slightly worse {response is slower & relapse is more common} 8-1]+2]normal 9-Insidious 10-1]❌ HTN 2]renal F is preserved 11-selective proteinuria 12-short course of corticosteroid therapy 13-steroid-dependent / steroid-resistant 14-focal & segmental glomerulosclerosis not detected by biopsy (diagnosis of MCD is wrong +if biopsy taken from another region in kidney may reveal FSGS not MCD ) 15-responsiveness to steroids