Glomerulonphritides Flashcards
Neuroblastoma characteristics
ALK gene - anapestic lymphoma kinase
adrenal medulla, sympathetic chain (paravertebral of abdomen, posterior mediastinum, pelvis, neck, brain
invade kidney, venal v., vena cava, envelop aorta
Homer-Wright pseudo rosettes
peripheral halo
Mets: lymph spread; blood to liver, lungs, bone marrow, bones; periorbital (proptosis, ecchymosis)
less than 2, large abdominal mass, fever, weight loss, older kids: mets S/S: bone pain, respiratory symptoms, GI complaints
Bladder/bowel dysfunction
neonates - blueberry muffin baby
Elevated serum catecholamines, elevated urine VMA and HVA
Unfavorable: MYCN amplification, Chr 1q and 11q loss, TRKB expression, mutations of neuritogenesis genes
Staging of NB
1: local, complete excision, LN negative
2A: local, incomplete excision, LN negative
2B: local, w/ or w/o complete excision, ipsilateral non adherent LN positive, enlarged contralateral LN
3: unresectable, cross midline, w/ or w/o LN OR local unilateral tumor w/ contralateral LN positive
4: distant LN involvement, bone, bone marrow, liver, skin involvement
4S: local tumor, dissemination limited to skin, liver and/or bone marrow - less than 1 yo
Wilms tumor genetics
WAGR: 11p13 deletion - WNT1, PAX6
DDS: dominant negative missense - zinc finger of WT1
BWS: 11q15.5 WT2 imprinting - loss of IGF2 imprinting = over expression); CDKN1C (p57 or KIP2) low risk
Beta-catenin - WNT - sporadic
Wilms tumor characteristics
Nephrogenic rests
Blastemal: small blue cells
Epithelial: abortive tubules or glomeruli
Stromal: fibrocytic or myxoid, sk.m. differentiation
Anaplasia - T53 mutation - resistance to chemo
Lower pole large expansile tumor
large abdominal mass, unilateral crossing midline, down to pelvis
hematuria, abd pain after trauma, intestinal obstruction, HTN
Pulmonary mets
Poor prognosis: anaplasia, Chr 11q, 16p loss; gain Chr 1q
WAGR syndrome
Wilms tumor, Aniridia, Genital anomalies, mental Retardation
Denys-Drash Syndrome
gonadal dysgenesis
early onset nephropathy leading to renal failure
diffuse mesangial sclerosis
Risk of WT and gonadoblastomas
Beckwith-Widemann Syndrome
Organomegaly macroglossia hemihypertrophy omphalocele adrenal cytomegaly
Risk: WT, hepatoblastoma, pancreatoblastoma, adrenocortical tumors, rhabdomyosarcoma
Post infectious Glomerulonephritis
Streptococcal pyogenic exotoxin B (speB)
Types 12, 4, 1 M protein
Elevated Antistreptococcal antibody titers
Decline in C3 concentration
elevated BUN
Granular IgG (IgA in staph) and C3 in GBM and mesagium
Early sub endothelial deposits, complex dissociates, crosses GBM, reforms as sub epithelial humps
nephritic syndrome
abrupt onset 1-2 weeks after sore throat
Adults: sudden HTN, edema
Good pasture syndrome (RPGNI)
Anti-GBM COL4-A3 antigen
HLA-DRB1
Diffuse linear IgG and C3
Fibrin crescents
Recurrent hemoptysis (lung hemorrhage)
RPGNII - immune complex
Granular immune complex deposition
influx of leukocytes in glomerular tuft
RPGNIII - pauci immune
ANCAs
no anti GBM antibodies or immune complexes
c-ANCA - Wegner’s - sinusitis
p-ANCA - asthma and polyangitis
Chronic Glomerulonephritis
90% cresentric GN
Hyalinized glomeruli
Contracted kidneys, thinned cortex, peripelvic fat
atrophy of tubules, irregular interstitial fibrosis
loss of appetite, anemia, V, weakness, edema
Membranous nephropathy
PLA2R antigen HLA-DQA1 Rising serum creatinine C5b-C9 MAC- capillary walls leaky Granular IgG4 and C3 diffuse Sub epithelial Ig deposits Effacement of podocyte foot processes Spikes and dones Segmental sclerosis Protein droplets in PT Nephrotic syndrome
Women- spontaneous remission, benign
SLE: self nuclear proteins and autoAb
Tumors: lung, colon, melanoma
Drugs: NSAIDs, penicillamine
Minimal change disease
Angiopoietin-like 4
Loss of foot processes
Nephrotic syndrome - albumine proteinuria
2-6
Follows respiratory infection or immunization
respond to corticosteroids or immunosuppressive tx
Focal Segmental glomerulosclerosis
Slit diaphragm protein mutations:
NPHS1: 19q13 - nephron
NPHS2 - 1q25-q31 - podocin - steroid resistance in kids
a-actinin -fast progression to renal insufficiency
TRPC6 - increase Ca2+ influx in podocytes
Focal IgM and C3
Loss of foot processes, focal detachment, epithelial denudation
Lipid droplets and foam cells
HIV, heroin, sickle cell, massive obesity
Risk: APOL1 Ch 22 varient, black
HIV associated nephropathy
collapsing glomerulopathy: retraction/collapsed glomerular tuft, micro cysts
tubuloreticular inclusions w/in endothelial cells (ER mods by INF-a)
Membranoproliferazive glomerulonephritis type I
splitting tram track
IgG and C3 granular pattern; C1q and C4
Sub endothelial deposits
MIXED nephrotic and nephritic syndromes
Secondary: chronic antigenemia, HBV, HCV w/ cryoglobinemia, HIV, schistosomiasis, SLE, endocarditis, infected ventriculoatrial shunts, chronic visceral abscesses, CLL, lymphomas, melanoma, a1-antitrypsin
Dense deposit disease (MPGNII)
Alternative complement pathway
C3NeF: properdin
Decreased serum C3, normal C1 and C4; decreased Factor B and properdin
Factor H mutations
GBM thickening, splitting
C3 granular or linear in GBM - C3 glomerulopathy
Dense deposits permeate GBM - ribbon like
C3 in mesangium
Nephritic syndrome - young
poor prognosis
IgA nephropathy
Defect O-link glycans to hinge of IgA1
activate alt complement pathway
IgA (IgG, IgM and C3/properidin) in mesangium- NO C1q and C4
coincident URI, GE, abscess
Berger Disease - no systemic
Henoch-Schonlein purpura: - skin (extensor arms, buttock, legs), and pain, V, GI bleed, arthralgia
Gluten enteropathy, liver disease
Alport Syndrome
AR, AD exist; X-linked
Chr 2 or 13, X: COL4A5 mutations - early ESRD
Moth-eaten, frayed, basket weave GBM and tubular BM, lamination of lamina dense focal thinning
X linked: Ab to A3, A4, A5 don’t stain; A5 in skin missing
Nerve deafness, eye: lens dislocation, posterior cataracts, corneal dystrophy
Thin Basement Membrane Lesion (Benign familial hematuria)
A3 or A4 COL4 mutations
diffusely thinned GBM -asymptomatic hematuria, mild-mod proteinuria
Diabetic nephropathy
advanced glycosylation end products
thick GBM and tubular BM
Diffuse mesangial sclerosis
Hemodynamic changes: glomerular hypertrophy leads to nodular glomerulosclerosis
Advanced renal hyaline arteriosclerosis: thick, tortuous AA
End stage: diffuse, granular, pitted surface, thin cortex, irregular cortical depression - pyelo
30% of all ESRD
Diffuse Proliferative Lupus Nephritis
Sub endothelial “wire loops” and mesangial dense deposits
large cellular glomerulus “stuffed” into Bowman’s capsule
Anti-IgG Ab to mesangial and capillary wall - sub endothelial
Recurrent hematuria
Nephritic/nephrotic
Fibrillary Glomerulonephritis
amyloid-like fibrils - mesangium, glomerular capillary walls
IgG4, C3 Igk, Iglambda light chain deposits
Nephrotic, hematuria, progressive renal insufficiency
