RENAL PATHOLOGY 1 Flashcards
Covers glomerular lesions - Powerpoints of Nephrotic, Nephritic and Systemic disorders involving the kidney
4 glomerular diseases presenting as nephritic syndrome
- Acute Proliferative (Postinfectious and Infection-Associated) Glomerulonephritis
- Immunoglobulin A (IgA) nephropathy
- Lupus nephritis
- Crescentic (Rapidly progressive) glomerulonephritis (RPGN)
a. Anti-GBM antibody–mediated disease
b. Complication of any of the immune complex nephritides
c. Pauci-immune - granulomatosis with polyangiitis, eosinophilic granulomatosis polyangiitis, microscopic polyangitis
Pathogenesis of primary membranous nephropathy
Antibodies to M-type phospholipase A 2 receptor (PLA 2 R)
Note: PLA2R is a a podocyte transmembrane receptor
Idenitfy the finding shown in the attached image
Fatty casts containing cholesterol droplets which are anisotropic and exhibit maltese cross appearance under polarized light.
1. What is your diagnosis?
History of Hep C infection
Palpable purpura + weakness + arthralgias
Type I MPGN
2. What is the composition of the immune complex deposits?
- Mixed cryoglobulinemic vasculitis
- Mixed IgG and IgM complex deposition.
2 key hemodynamic changes assoc with diabetic nephropathy
Glomerular hyperfiltration
Glomerular hypertension
List 3 pauci immune crescentic glomerulonephritic lesions
- Granulomatosis with polyangiitis (formerly Wegener granulomatosis)
- Microscopic polyangiitis
- Eosinophilic granulomatosis with polyangiitis (formerly Churg Strauss)
Nephritic/ Nephrotic?
Edema, hyperlipidemia
Free fat, oval fat bodies on urinalysis
>3.5g/24 h proteinuria
Nephrotic Syndrome
Most common cause of ESRD in the United States
Diabetic nephropathy
Pathogenesis of Anti- GBM mediated disease
autoantibodies specific for the NC1 domain of the α3 chain of type IV collagen
Characteristic renal morphology assoc with ANCA assoc vasculitis
Pauci immune type of crescentic (rapidly progressive) glomerulonephritis
Renal amyloidosis presents as nephrotic or nephritic syndrome?
Nephrotic syndrome (60%)
Type of hypersensitivity assoc with Goodpasture syndrome
Type II - §complement, and Fc receptor mediated inflammation induces damage.
What is responsible for the finding seen in the image?
The image indicates crescent formation.
Crescents form due to proliferation of parietal epithelial cells derived from lining of Bowman’s capsule and influx of macrophages
What’s your diagnosis?
Chronic sinusitis
Hemoptysis
CXR: bilateral nodular and cavitary infiltrates
Hematuria, RBC casts
Renal biopsy: crescentic glomerulonephritis
Granulomatosis with polyangiitis (GPA)
Nephritic/ nephrotic?
Glomerular hematuria + RBC casts+ Dysmorphic RBCs+ variable proteinuria +renal insufficiency + hypertension.
Nephritic Syndrome
What will you see on Electron microscopy in the condition described?
58 year old male
Nephrotic range proteinuria
Seropositive for Hep B
LM shows uniform , diffuse thickening of the glomerular capillary wall
Diagnosis: Membranous nephropathy
EM: Subepithelial deposits, spike and dome pattern
What is the underlying defect associated with the condition described?
Hypertension, RBC casts, Hematuria
Bilateral sensorineural hearing loss
anterior lenticonus
Diagnosis: Alport Syndrome
Defect: Mutations that interfere with assembly of type IV collagen
Why does edema develop in nephrotic syndrome?
Increased permeability of glomerular capillary wall –>proteinuria–>hypoalbuminemia–>decreased intravascular colloid osmotic pressure–> edema
Why do patients with nephrotic syndrome develop hyperlipidemia?
Increased lipoprotein synthesis
Decreased lipid catabolism
Abnormal transport
- Type of amyloid assoc with hemodialysis
- Most common presentation of amyloidosis assoc with hemodialysis
- β 2 -microglobulin
- Carpal tunnel syndrome
Morphology of spleen in SLE
onion skin lesions due to concentric intimal and smooth muscle cell hyperplasia of central penicilliary arteries
1. What’s your diagnosis?
6-10 years, post pharyngeal/ skin infection
LM: See attached image
2. Why is there a decline in the serum concentration of C3 in this condition?
- Post streptococcal glomerulonephritis
- Activation of the complement system and consumption of complement components.
EM finding assoc with dense deposit disease
Intramembranous deposition of a ribbonlike, homogeneous, extremely electron-dense material of unknown composition as well as in the mesangium
EM finding in FSGS
Effacement of foot processes
decreased glycosylation of O-linked glycans in the hinge region of the IgA1 molecule
IgA nephropathy (Berger disease)
Which glomerular lesion of diabetic nephropathy is being described below?
LM: ovoid or spherical, PAS-positive nodules of mesangial matrix at periphery of the glomerulus
Nodular Glomerulosclerosis aka Kimmelstiel-Wilson disease
Most frequent cause of nephrotic syndrome in children
Minimal change disease
Chronic sinusitis
Hemoptysis
CXR: bilateral nodular and cavitary infiltrates
Hematuria, RBC casts
Renal biopsy: crescentic glomerulonephritis
Antibodies assoc with this condition?
PR3 ANCAs
(Wegener granulomatosis)
List 2 important secondary causes for Membranous nephropathy
Drugs- Penicillamine, Gold
Infections- Hepatitis B and C
List 2 antibodies specific for SLE
Anti dsDNA
Anti-Smith
Why is nephrotic syndrome assoc with an increased risk of thrombosis?
Loss of AT III in urine
What do the immune complex deposits in Berger disease contain?
IgA and C3
Type of hypersensitivity mechanisms operational in SLE
- Type III - caused by immune complexes
- Type II - Autoantibodies specific for blood cells àopsonize these cells –>phagocytosis and destruction –> cytopenias
3 secondary causes for FSGS
HIV, Obesity, Sickle cell disease
Underlying mechanism of neonatal lupus
transplacental passage of maternal IgG autoantibodies to SSA/Ro and/or SSB/La intracellular ribonuclear proteins
Which malignancy may be associated with Minimal change disease?
Hodgkin Lymphoma
What’s your diagnosis?
Microscopic hematuria 1-2 days after an URTI
Complement levels normal
Proteinuria, dysmorphic RBCs, RBC casts are present.
LM: See attached image
Diagnosis: IgA nephropathy
LM shows mesangial widening due to accumulation of amtrix+ immune complex deposits+cell proliferation.
earliest clinical sign of the development of diabetic kidney disease
the onset of microalbuminuria
4 renal complications of diabetes
- Diabetic nephropathy
- Type 4 (hyporeninemic, hypoaldosteronemic) metabolic acidosis with hyperkalemia
- increased incidence of bacterial and fungal infections of the genitourinary tract
- increased risk for pyelonephritis
- papillary necrosis
Morphologic finding assoc with diffuse lupus nephritis on Light microscopy
circumferential capillary wall thickening–> ‘wire looping’
Subendothelial deposits
Proliferation of epithelial cells- crescents
Hereditary FSGS is assoc with which mutation?
Mutations in genes that encode proteins localized to the slit diaphragm – nephrin, podocin.
Most common cause of glomerulonephritis worldwide
Immunoglobulin A (IgA) nephropathy
1 persistent Clinical manifestation of neonatal lupus
Congenital heart block
Cause for hypocomplementemia in lupus nephritis
During acute flareups, increased formation of immune complexes results in complement activation, often leading to hypocomplementemia.
3 categories of Crescentic (Rapidly Progressive) Glomerulonephritis
I.Anti-GBM antibody mediated
II.Immune complex–mediated
III.Pauci-immune
Most common cause of nephrotic syndrome in the elderly
Membranous nephropathy
What is your diagnosis?
45 year old male
History of Hepatitis C infection
Hematuria, periorbital and pedal edema, hypertension
LM: Duplication of the basement membrane and hypercellular glomeruli
EM: discrete subendothelial deposits
IF: IgG and C3 in granular pattern
Type I MPGN
What will you see on EM?
4 year old child
5g/24h proteinuria that follows a respiratory tract infection
EM: effacement of foot processes in visceral epithelial cells
What’s your diagnosis?
asthma, allergic rhinitis, lung infiltrates, peripheral hypereosinophilia, extravascular necrotizing granulomata
Increased serum IgE level
Renal biopsy: crescentic glomerulonephritis
MPO ANCA present
Eosinophilic granulomatosis with polyangiitis
IF pattern in Anti-GBM mediated disease
Linear deposits of IgG
How does hyperglycemia lead to formation of excess basement membrane material ?
- Advanced glycation end products (AGEs) bind to RAGE on Tcells and macrophages–> TGF-beta—> excess BM material
- Advanced glycation end products (AGEs) bind to RAGE on vascular smooth muscle cells–> synthesis of ECM
- Advanced glycation end products (AGEs) directly cross link ECM proteins–> resiatnt to digestion–> accumulate
What’s your diagnosis?
Palpable purpura on buttocks and lower extremities
Arthritis
colicky abdominal pain
Renal biopsy: mesangial deposits of IgA
Henoch Schonlein Purpura (IgA vasculitis)
Pathogenesis of Dense Deposit Disease (Type II MPGN)
Presence of a circulating autoantibody called C3 nephritic factor
Most common cause of idiopathic nephrotic syndrome in adults especially Hispanic and African-American polulation
Focal Segmental Glomerulosclerosis
What’s your diagnosis?
6-10 year old child, post pharyngeal/ skin infection
LM: enlarged, hypercellular glomeruli
IF: Granular deposits of IgG and C3
What’s the location of deposits on EM?
Post streptococcal glomerulonephritis
subepithelial deposits, forming “humps”
Morphologic finding assoc with renal amyloidosis
eosinophilic acellular confluent masses or interlacing broad ribbons in the glomeruli
3 hallmark glomerular lesions assoc with diabetic nephropathy
- Capillary basement membrane thickening
- Diffuse mesangial sclerosis
- Nodular glomerulosclerosis
Morphology of HIV assoc nephropathy
FSGS+ focal tubular segment dilation filled with proteinaceous material
