Renal Pathology 3: Glomerular Disease (Dobson) Flashcards
Renal visceral epithelial cells in the corpuscle
Podocytes - part of the renal corpuscle that prevents large negatively charged proteins (ex albumin) from being filtered
What are the components of the glomerular basement membrane (GBM)
predominantly collagen type IV; laminin, and other proteins
Hyalinosis
accumulation of material that is homogenous and eosinophilic by LM; typically this is the end result of various forms of glomerular damage
Sclerosis
characterized by the deposition of ECM (type IV) collagen; stains with trichrome stain; typical builds up in mesangial areas (diabetic glomerulosclerosis)
Glomerulosclerosis
sclerosis in the mesangial areas (seen in diabetic glomerulosclerosis)
Nephritic Syndromes clinical features
Usually sicker;
Hematuria
Proteinuria +/- edema (periorbital)
Azotemia
HTN
Post-streptococcal glomerulonephritis
Nephritic syndrome; symptoms occur 1- 3 weeks following a group A strep (strep pyogenes) infection (strep throat - pharyngitis or impetigo - skin infection); deposits are seen in both subendothelium AND subepithelium (“sub epithelium hump”); coca cola hematuria
Goodpature syndrome
both kidney and lung involvment; anti-GBM against collagen type IV; IF shows linear pattern; causes RPGN
SLE
causes nephritic syndrome (if nephrotic think membranous nephropathy); diffuse proliferative glomerulonephritis is the most common presentation of lupus nephritis; DNA anti-DNA IC deposition; steroid tx
“wire loop” structures on light microscopy
DNA anti-DNA IC deposition seen in lupus nephritis that caused diffuse proliferative glomerulonephritis seen in nephritic syndrome
Henoch-Schonlein Purpura (HSP)
Nephritic syndrome; causes renal disease similar to IgA nephropathy; IgA vasculitis syndrome characterized by rash, abdominal pain, arthritis and nephritis; characteristic LE palpable purpura;
IgA nephropathy
Nephritic syndrome; Berger disease or IgAN; affects children and young adults; IC deposits in the mesangium; upper respiratory or GI infection and then hematuria 1-2 days later; episodic gross hematuria
ANCA disorders
Wegener’s granulomatosis (c-ANCA)
Microscopic polyangiitis (p-ANCA)
both can cause RPGN Type III
Nephrotic syndrome clinical features
Massive proteinuria ( > 3.5g)
Hypoalbuminemia
Generalized edema
Hyperlipidemia and lipiduria
Membranous Nephropathy
most common nephrotic syndrome in white adults; usually idiopathic; antibody binding to PLA2R; can be associated with Hep. B or C, lupus, or drugs. Thick glomerular membranes on H&E (usually thin), due to immune complex deposition; granular IF, “spike and dome” appearance on EM
Minimal Change Disease
most common cause of nephrotic syndrome in children; usually idiopathic; may be associated with Hodgkin lymphoma; cytokines mediate damage to the podocytes.
Hallmark: normal glomeruli on H&E stain (barely see any change “minimal”) but may see effacement of the foot processes on EM
Treatment: excellent response to STEROIDS b/c damage is mediated by cytokines
Focal Segmental Glomerulosclerosis (FSGS)
most common nephrotic syndrome in Hispanics and African Americans; usually idiopathic; may be associated with HIV, heroin use, and sickle cell disease*.
focal and segmental sclerosis on H&E; effacement of foot processes on EM; does NOT respond to steroids (unlike with minimal change disease); progresses to chronic renal failure
Treated with Renin-Angiotensin System inhibitors
Collapsing variant of FSGS
AKA HIV associated nephropathy
Kimmelstiel-Wilson nodules
nodular glomerulosclerosis AKA Kimmelstiel-Wilson nodules seen in diabetic nephropathy; basically pink round deposits of laminated mesangial matrix
Membranoproliferative Glomerulonephritis (MPGN)
Nephrotic syndrome (mixed) - thick capillary membranes on H&E with a “tram track” or “double-contour” appearance due to immune complex deposition (granular IF); can progress to ESRD
Type 1: HBV/HCV and more often associated with tram track appearance (Nephrotic)
Type 2: C3NeF found in patients. (Nephritic) AKA as dense-deposit disease
“tram track” or “double-contour” appearance on H&E
Membranoproliferative Glomerulonephritis (MPGN) type 1 - seen in Nephrotic Syndrome
C3 Nephritic factor
C3NeF is associated with type 2 Membranoproliferative Glomerulonephritis (MPGN) in nephritic syndrome AKA dense deposit disease
Alport syndrome
X linked inherited defect in type IV collagen (del COL4A5); thinning and splitting of the GBM; “basket-weave” appearance; presents as isolated hematuria, sensory hearing loss and ocular disturbances
Diabetic nephropathy
Nephrotic syndrome; nodular glomerulosclerosis by Kimmelstiel-Wilson nodules on LM; leading cause of end-stage renal disease (ESRD)
Treatment for minimal change disease
Treatment: excellent response to STERIODS b/c damage is mediated by cytokines; only nephrotic syndrome where you get an excellent response to treatment
Patient with HIV that develops nephrotic syndrome; what is on your differential diagnosis?
Focal Segmental Glomerulosclerosis; the most common nephrotic syndrome in Hispanics and African Americans; usually idiopathic; may be associated with HIV*, heroin use, and sickle cell disease.
“spike and dome” appearance on EM
Membranous Nephropathy - nephrotic syndrome
Systemic Amyloidosis
Amyloid deposits in mesangium resulting in nephrotic syndrome; characterized by apple-green birefringence under polarized light.
In what disorders are subepithelial deposits seen?
Membranous glomerulopathy
Minimal change disease (MCD)
Focal segmental glomerulosclerosis (FSGS)
What adaptive changes do you see in acute kidney injury?
Hypercellularity; proliferation of mesangial or endothelial cells; and formation of crescents* = RPGN (very quick onset)
What adaptive changes do you see in chronic kidney injury?
LM: thickening of the capillary walls as seen with PAS staining
EM (better diagnostic tool with chronic injury): deposition of electron-dense material and
-focal nodular glomerulosclerosis with diffuse glomerulosclerosis (diabetes)
What differential should come to mind when there is focal nodular glomerulosclerosis with diffuse glomerulosclerosis on EM?
Diabetes nephropathy
Explain pathophysiology of nephrotic syndrome to L varicocele.
decrease of antithrombin III, leads to a hypercoagubule state, renal vein thrombosis (RVT), if L renal vein is involved, can lead to blockage of the L testicular v and can then lead to L varicocele
Clinical presentation of Minimal Change Disease
10 year old kid who experienced flu-like symptoms about two weeks ago now presents with generalized edema. Check urine and there is proteinuria. Check blood and there is hypoalbuminemia.
What would the LM show in the case of Focal Segmental Glomerulosclerosis (FSGS)
obliterated capillaries with hyaline deposition; urine test would show non-selective proteinuria.
the term “diffuse”
involving all of the glomeruli in the kidney
the term “global”
involving the entirety of individual glomeruli
the term “focal”
involving only a fraction of the glomeruli in the kidney
the term “segmental”
affecting a part of each glomerulus
the term “capillary loop or mesangial”
affecting predominantly capillary or mesangial regions
IF microscopy of classic anti-GBM disease
In what disorders are subendothelial deposits seen?
lupus nephritis and membranoproliferative glomerulonephritis (MPGN)
In what disorders are mesangial deposits seen?
IgA nephropathy
Podocytopathy is a feature in what types of glomerular injury?
Podocytopathy = epithelial cell injury = loss of podocytes
seen in FSGS, HIV, and Diabetic nephropathy
the term “granular” on IF should make you think of what?
immune complex deposition
Where is IgA usually secreted
IgA is normally secreted by mucus membranes (think upper respiratory or GI infection)
What is a huge characteristic of Henoch-Schonlein Purpura (HSP)?
Lower extremity palpable purpura
Focal or diffuse mesangial proliferation on microscopy?
IgA nephropathy; post-strep GN, membranoproliferative glomerulonephritis (MPGN), dense deposit disease
Treatment for IgA
Glucocorticoids (steroids)
Deposits in both subendothelium AND subepithelium (“sub epithelium hump”) should make you think of what?
Post streptococcal glomerulonephritis
What test should you order if you suspect Post streptococcal glomerulonephritis?
serum anti-STREPtolysin-O (ASO) and anti-DNase B titers (elevated after group A strep infection)
What is the most common pattern seen in lupus nephritis?
diffuse proliferative glomerulonephritis seen in nephritic syndrome
DNA anti-DNA immune complex deposition in the subendothelial space should make you think of what?
lupus nephritis that caused diffuse proliferative glomerulonephritis seen in nephritic syndrome
LM shows mesangial hypercellularity and enlarged lobular glomeruli should make you think what?
Membranoproliferative Glomerulonephritis (MPGN)
Dense-deposit disease
Membranoproliferative Glomerulonephritis (MPGN) type II; deposition of unknown material in the basement membrane (causes thickening); EM would look like a thick black line
Rapidly Progressive Glomerulonephritis (RPGN) on LM
segmental necrosis and breaks in the glomerular basement membrane
Fibrin deposits and crescent formation should make you think what?
Rapidly Progressive Glomerulonephritis (RPGN)
sub-epithelial hump seen in Post-Streptococcal Glomerulonephritis in Nephritic syndrome; deposits are seen in both subendothelium AND subepithelium
H&E of crescent-shaped mass, seen in Rapidly Progressive Glomerulonephritis (RPGN) AKA Crescentic glomerulonephritis
RPGN Type I
Anti-GBM antibody mediated; Goodpasture syndrome; involves kidney and lung; IF linear pattern
RPGN Type II
Immune complex deposition mediated; think SLE (anti-dsDNA antibodies) or Henoch-Schonlein Purpura (HSP)
wire loop pattern on LM; SLE (anti-dsDNA); causes RPGN Type II
IF of IgA deposits in the mesganium; seen IgA nephropathy in nephritic syndrome (Berger Disease)
RPGN Type III
Glomerular lesions associated with systemic disease; think ANCA disorders; Wegener’s granulomatosis (c-ANCA) and Microscopic polyangiitis (p-ANCA); both will have a negative IF (unlike type I and type II)
“spike and dome” appearance on EM; membranous nephropathy seen in nephrotic syndrome
H&E of Focal Segmental Glomerulosclerosis (FSGS) seen in nephrotic syndrome
Kimmelstiel-Wilson nodules seen in diabetic nephropathy in nephrotic syndrome
H&E with a “tram track” or “double-contour” appearance due to immune complex deposition; seen in type I MPGN (nephrotic)
EM of ribbon-like, homogenous, extremely electron-dense material of unknown composition seen in type II MPGN (nephritic) AKA dense deposit disease
Isolated hematuria, sensory hearing loss and ocular disturbances in a family should make you think of what?
Alport Syndrome; X linked; will see thinning and splitting of the GBM “basket-weave” appearance
“basket-weave” appearance; thinning and splitting of the GBM as seen in Alport syndrome
