Week 3: Nephrotic Syndrome Flashcards
1
Q
Describe general pathologic features of nephrotic syndrome.
A
- obliteration of visceral epithelial cell foot processes and swelling of epithelial cells
- tubular protein reabsorption droplets in PT
- oval fat bodies: lipid within tubular epithelial cells and peritubular macrophages –maltese cross
2
Q
List the diseases usually associated with nephrotic syndrome.
A
- primary
- minimal change
- focal segmental glomerulosclerosis
- membranous nephropathy - Secondary
- diabetic glomerulosclerosis
- amyloidosis
3
Q
Describe clinical features of minimal change disease.
A
-most common cause of nephritic syndrome in young children
-acute onset, usually follows URI. GFR normal.
-look for secondary causes in adults: NSAIDs, lithium, infectious mono, immunizations, Hodgkin disease
-Few or no glomerular abnormalities by light microscopy, electron microscopy shows epithelial foot process obliteration
-
4
Q
Describe pathologic features of minimal change disease.
A
- EM shows obliteration of visceral epithelial cell foot proceses
- biopsy showing minimal changes doesn’t exclude FSGS
- lipid droplets in PT epithelial cells, oval fat bodies, increased protein reabsorption droplets
5
Q
Pathogenesis of minimal change disease.
A
- Targeted podocyte injury–Dysfunction in T cell immunity
- abnormal T lymphocyte clone produces cytokine that induces podocyte damage, reorganization of podocyte actin cytoskeleton, reversible effacement of podocyte foot processes
- loss of anionic charge of basement membrane
6
Q
Clinical features of focal segmental glomerulosclerosis (FSGS).
A
- scarring of some glomeruli in which a segment or portion of glomerular tuft is affected
- 5% of nephrotic children and 15% nephrotic adults
- non selective proteinuria, microscopic hematuria, reduced GFR, and HTN
- Definition: A sclerosing lesion, associating with proteinuria, typically involves segments of some glomeruli
7
Q
Etiology of FSGS
A
- Primary and Secondary types
- Secondary: obesity, heroin nephropathy, HTN, reflux, HIV nephropathy, unilateral renal agenesis
- steroids are usually non effective
- ESRD develops 5-20 years after presentation
8
Q
Pathological features of FSGS
A
- need renal biopsy for diagnosis
- sample size is important because it is focal
- usually affects juxtamedullary glomeruli
- segmental collapse of glomerular tuft
- hyaline lesions and foam cells may be present within sclerotic lesions
- IgM and C3 staining
- EM: capillary collapse, subendothelial and mesangial electron dense deposits, epithelial foot process obliteration
9
Q
Pathogenesis of FSGS
A
- podocyte injury and depletion
- podocytes are highly differentiated, limited replication ability. Loss of podocytes leads to bare and leaky GBMs
- possibly due to circulating permeability factor (cytokine)
- genetic mutations in podocyte structural proteins: nephrin, podocin, a-actinin4
- secondary FSGS: glomerular hyperfiltration and secondary podocyte stress, e.g. HTN
10
Q
Clinical features of collapsing glomerulopathy
A
- variant FSGS with poor prognosis and serve proteinuria, rapid loss of renal function, and non responsive to steroid treatment
- at least one glomerulus shows segmental or global glomerular tuft collapse or implosion, with overlying podocyte hypertrophy and hyperplasia
- preponderance in african americans: linked to allelic variants in Chromosome 22, MYH9 encoding myosin heavy chain 9 and APOL1
- Secondary lesion in : viral infection (HIV, Parvo, CMV), drug toxicities, renal allografts
11
Q
Pathogenesis of collapsing glomerulopathy
A
- direct infection of podocytes by virus (e.g. HIV)
- indirect damage to podocytes by cytokines
- African Americans: allelic variants in chrom 22: MYH9 site encoding myosin heavy chain 9 and APOL1
- APOL1 gives resistance to trypanosomal infection
- allelec variants of APOL1 comes at cost of increased risk of FSGS
12
Q
Clinical features of membranous nephropathy.
A
- diffuse thickening of capillary walls of glomeruli produced by subenpithelial immune deposits and associated basement membrane reaction
- frequent cause of nephrotic syndrome in adults
- age 40-60 yo, male>female
- Clinical findings: Nephrotic syndrome (80%), HTN uncommon, renal function usually normal at presentation, renal vein thrombosis that can lead to PE
13
Q
Etiology of membranous nephropathy.
A
- Idiopathic 15-20%
- Secondary
- Immunological disorders: SLE, RA
- neoplasms: carcinoma, Non-Hodgkins lymphoma
- Infections: Hep B
14
Q
Pathology of membranous nephropathy.
A
- early disease: may appear normal by light microscopy
- capillary walls become thickened by sub epithelial (betw podocytes making up visceral epithelium and BM) deposits and the BM reaction to them
- holes, “spikes” in silver stain from where BM is destroyed and new BM is being made
- podocytes try to manufacture BM by putting cytoplasm in between BM,
- deposits washed out by blood flow, and left with thickened BM
- effaced foot processes, microvillous changes
- rarely crescent formation, which can be seen in late stage or may be associated with anti-GBM disease
- granular capillary wall staining for IgG and C3–>immune complexes
15
Q
Pathogenesis of membranous nephropathy
A
2 mechanisms
- in situ: local antigen released from visceral epithelial cells in primary disease.
- antibodies to M type phopholipase A2 receptor (PLA2R) occur in 75% of patients with primary MN. PLA2R is receptor glycoprotein found on podocytes and type II pneumocytes and leukocytes
- Circulating IgG4 antibodies against (autoimmune) - Planted antigen: extrinsic circulating antigen that is trapped in sub endothelial location because of size and charge, a circulating antibody IgG penetrates the BM to complex with it. Known antigens: Hep B, CEA, DNA, thyroid antigens
- (note: IgG can pass the BM but IgM cannot)
