2: Renal Path 2 - GN Flashcards
Gross and micro appearance of cystic renal dysplasia
Gross: enlarged, multi-cystic, irregular.
Micro: variably sized cysts lined by flattened epithelium
Etiology of cystic renal dysplasia
Sporadic
Inheritance and presentation of adult PCKD
AD, bilateral but involving only a portion of the kidney initially, multiple expanding cysts destroy parenchyma
What percent of ADPCKD patients have renal failure at age 75
75%
How are cilia involved in adult PCKD?
Normally keep cells oriented toward lumen, polycystin muts -> cilia defects -> secretion into inappropriate spaces
Micro appearance of adult PCKD
Cysts with variable lining arising from tubules, normal parenchyma between cysts
Clinical presentation of adult PCKD
Asymptomatic or pain, hematuria
Adult vs childhood PCKD: gross apperance of kidneys
Adult: bag of cysts, lumpy appearance. Children: smooth but enlarged externally, x-sect shows many sm cysts in cortex and medulla
Extra-renal anomalies with adult PCKD (3)
Liver cysts (40%), berry aneurysms (cause of death for 4-10%), mitral prolapse (20-25%)
Childhood PCKD inheritance and micro findings
AR. Dilation of all collecting tubules. Gross: bilateral issue.
Complications of childhood PCKD
Nearly all pts: Liver cysts and bile duct proliferation. Some: congen hepatic fibrosis, periportal fibrosis
What is medullary sponge kidney? Who gets it?
Multiple cystic dilations of collecting ducts. Adults.
Symptoms of medullary sponge kidney
asymptomatic or hematuria, infection, stone formation. Normal kidney fx.
What is nephronophthisis- uremic medullary cystic disease complex?
Cysts in medulla + cortical tubular atrophy + interstitial fibrosis. Onset in childhood, progressive.
Presentation of nephronophthisis- uremic medullary cystic disease complex
Polyuria and polydipsia due to the tubular defect
What should you think of for children with polyuria?
Tubular defect
What is acquired cystic disease? What is another name for it?
Dialysis-associated cystic disease. 7% of dialysis pts will devel renal cell carcinoma w/in the cysts in 10 years
Usual size and location of renal simple cysts
1-5 cm usually cortical, clear fluid
GN is ____ mediated
immune, hypersensitivity II and III, not usually T-cell (IV)
What are crescents?
proliferations of epithelial cells and infiltrating WBCs
Define global and segmental with regards to glomerular pathology
Segmental: part of a single glomerulus involved.
Global: Entire single glom involved.
What does trichrome stain highlight? What color?
Blue-green basement membrane
How does IF appear with Goodpasture syndrome?
Homogeneous, diffuse, ribbon-like (even, not patchy)
Why is there hemoptysis in Goodpasture syndrome?
Ab cross reacts with basement membrane of pulmonary alveoli
What happens in membranous nephritis?
Autoantibody to M-type phospholipase A2 receptor in kidney -> activation of complement -> damage
How does membranous nephritis appear on IF? EM?
IF: granular, interrupted
EM: subepithelial electron dense deposits
What are planted antigens?
Non-glomerular origin but plant in kidney where antibodies attack them e.g. DNA, bacterial products such as exotoxin
What is circulating immune complex nephritis? What type of hypersensitivity?
Circulating Ag-Ab complexes get trapped in glomerulus. Type III.
Circulating immune complex nephritis IF and EM
IF: granular deposits
EM: mesangial, subepithelial or subendothelial deposits
What types of nephritis can result in mesangial deposits?
Circ immune complex, Type I MPGN
What types of nephritis can result in subepithelial deposits?
Circ immune complex, membranous, Type I MPGN
What types of nephritis can result in subendothelial deposits?
Circ immune complex, possible in RPGN, Type I MPGN
What is now known about the rate of progression in glomerular disease?
Once GFR reduces to 30-50%, progression to ESRD is at a steady rate regardless of cause
Histological findings of ESRD
- Focal segmental glomerulosclerosis (FSGS)
2. Tubulointerstitial fibrosis
How does FSGS develop
Dec nephron fx -> compens hypertrophy -> hemodynamic change -> segmental sclerosis w cell injury, epithelial loss, accum of proteins
How is FSGS treated?
Renin-angiotensin inhibitors slow progression but do not cure
How does tubulointerstitial fibrosis develop?
Glom issues -> ischemic tubules downstream of sclerotic gloms + toxic effects of proteinuria -> inc acute & chron inflam -> scarring, fibrosis
Nephritic syndrome is caused by diseases that are ____ and ____ e.g. ____
inflammatory and proliferative e.g. post-infectious
What is another name for acute poststreptococcal GN?
Post-infectious GN (not always due to strep)
What happens in post-strep GN?
1-4 weeks post pharyngeal or skin infec w/ certain strains of Gr A beta hemolytic strep -> nephritis
What serum findings are present in acute post-strep GN?
Low: complement (C3)
High: antistreptolysin O, antiDNase B
Post-strep GN histology (3)
Large hypercellular glom, prolif of endothelial and mesangial cells, infiltration of neutrophils and monocytes
Post-strep GN IF
Granular with IgG, IgM, C3 deposits (types not import) in mesangium + along GBM
EM of post-strep GN
Supepithelial humps “camel” IMPORTANT Also subendo and intramembranous deposits
Clinical presentation of post-strep GN
Periorbital swelling, malaise, oliguria, “smokey” hematuria, mild HTN, mild proteinuria, red cell casts
Prognosis of post-strep GN
95% and 60% full recovery of renal fx in kids and adults respectively
What is another name for rapidly progressive GN (RPGN)?
Crescentic
What happens to the glom in RPGN?
> 50% of glom have crescents - prolif of parietal epithelial cells of BC + inflam cells
Cause of RPGN?
No specific entity
What is Type I RPGN? IF?
Anti-GBM GN. IF: linear ribbon-like deposits in GBM
What is Type II RPGN? IF?
Immune comp mediated e.g. PSGN, SLE, IgA nephropathy. IF: lumpy-bumpy, granular
What is Type III RPGN? IF?
Pauci-immune type. Lack of IF staining. Most have P- or C-ANCA
In Type III RPGN, will there be signs of vasculitis or glom damage first?
Can go either way. May have ANCA pos RPGN without signs of systemic involvement
RPGN gross features
Large, pale kidneys with petechiae
RPGN micro features
> 50% of gloms with crescent formation with fibrin strands
RPGN EM features
Possible ruptures in GBM, with or w/o subepithelial deposits
RPGN clinical presentation
Nephritic: hematuria, red cell casts, mod proteinuria, HTN, edema
RPGN clinical course
Progressive over weeks with severe oliguria
RPGN treatment
Anti-GBM: plasma exchange, steroids, chemo
Why is there increased risk of infections + hypercoagulable state in nephrotic syndrome?
loss of Ig and complement via proteinuria, loss of anticoagulants esp anti-thrombin III
Most common cause of nephrotic syndrome in children
Minimal change disease
Most common nephrotic syndrome in adults
Focal segmental glomerulosclerosis - pts w various renal disease progress to FSGS. #2 is membranous GN
Secondary causes/ assocs for membranous GN
Drugs (penicillamine, captopril, gold, NSAIDs), malignancy (lung, colon, melanoma), SLE, infections, metabolic (DM, thyroiditis)
Pathogenesis of membranous GN
IC-mediated, (end or exogenous Ag) often phospholipase A2 receptor of podocytes
What is the cause of GBM damage in Membranous GN?
Complement-mediated
Microscopic findings in membranous GN
Normocellular gloms + uniform diffuse thickening of capillary wall (Cheerios look) + Spikes on silver stain (BM between deposits)
Later microscopic findings in membranous GN
Deposits turn into a very thickened GBM. Late: mesangial sclerosis, glom hyalinization
Membranous GN IF
Granular deposits along GBM with IgG and C3
Membranous GN EM
Subepithelial deposits, later spikes of BM grow between deposits, then thickened GBM + foot process effacement
Treatment for membranous GN
If secondary, treating cause can resolve. Otherwise corticosteroids are +/-
Typical course of membranous GN
Slow deterioration, chronic proteinuria
What is the other term for Minimal Change Disease?
Lipoid Nephrosis
What is minimal change disease? Peak age?
Poss T cell dysfx -> cytokines -> damage to visc epithel cells -> loss of charge barrier/ adhesion defects between epithelial cells
MCD associations
Atopy (eczema, rhinitis), post resp infec or routine immunization, inc incidence in Hodgkin lymphoma
Treatment of MCD?
Corticosteroids reverse damage to podocytes
Peak age for MCD
2-6 years
MCD micro findings
Normal gloms, prox tubules may be filled with lipid
MCD IF
No staining. No deposits.
EM in MCD
Diffuse effacement of podocyte foot processes. No deposits.
Clinical course of MCD
Massive proteinuria (mostly albumin), no renal failure, often no HTN
FSGS associations (4)
HIV, heroin addiction, sickle cell disease, morbid obesity
Hallmark of FSGS
Damage to visceral epithelial cells
What genetic abnormalities predispose to FSGS?
Muts of proteins that localize to slit diaphragm e.g. nephrin and podocin
Some put FSGS on a spectrum with what? Which is more severe?
MCD (less severe) – FSGS
Micro findings in FSGS
Need large biopsy (focal). Collapsed GBM, inc mesangial matrix, hyalinization (Magenta w PAS) +/- foam cells
EM findings in FSGS
Diffuse effacement of foot processes, focal detachment of epithelial cells from GBM
IF in FSGS
Mesangial deposits of IgM and C3 in affected area
FSGS clinical presentation
Nephrotic syndrome, HTN, dec GFR, poor response to corticosteroids
Which renal issues recur post transplantation?
FSGS
HIV nephropathy most common renal complication
FSGS
HIV nephropathy micro findings
Cystically dilated tubules filled w proteinaceous material + inflammation
HIV nephropathy EM
Tubuloreticular inclusions in endothelial cells (nearly pathognomonic, also in SLE)
What is membranoproliferative GN?
Prolif of glomerular cells + leukocyte infiltration + GBM changes
Membranoproliferative GN clinical presentation
Mixed nephrotic - nephritic
MPGN associations (4)
SLE, HepB, HepC, malignancy
Microscopic appearance of MPGN (similar type I & II)
Large, hypercellular glom w lobular architecture, thickened GBM w “tram track” of mesangial cell into GBM
EM of Type I MPGN
Subendothelial deposits +/- supepith and mesangial
