Renal - Pathology (Nephrotic & Nephritic syndromes) Flashcards
Pg. 536-538 in First Aid 2014 Pg. 490-492 in First Aid 2013 Sections include: -Nephrotic syndrome -Nephritic syndrome
How does nephrotic syndrome present?
NephrOtic syndrome presents with (1) massive prOteinuria (>3.5g/day, frothy urine), (2) hyperlipidemia, (3) fatty casts, (4) edema
With what 2 other conditions is nephrotic syndrome associated, and why?
Associated with (1) thromboembolism (hypercoagulable state due to AT III loss in urine) and (2) increased risk of infection (loss of immunoglobulin)
What characterizes focal segmental glomerulosclerosis on light microscopy? What characterizes it on electron microscopy?
LM - Segmental sclerosis and hyalinosis; EM - Effacement of foot process similar to minimal change disease
What characterizes membranous nephropathy on light microscopy? What characterizes it on electron microscopy?
LM - Diffuse capillary and GBM thickening; EM - “spike and dome” appearance with subendothelial deposits
How does membranous nephropathy appear upon immunofluorescence? With what condition’s presentation is this immunofluorescence associated?
Granular; SLE’s nephrotic presentation
What characterizes minimal change disease on light microscopy? What characterizes it on electron microscopy?
LM - Normal glomeruli (lipid may be seen in PCT cells); EM - Foot process effacement
What characterizes amyloidosis on light microscopy?
LM - Congo red stain shows apple-green birefringence under polarized light
What characterizes diabetic glomerulonephropathy on light microscopy?
LM - mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesion).
What are the 6 glomerular diseases primarily classified as nephrotic syndrome?
(1) Focal segmental glomerulosclerosis (2) Membranous nephropathy (3) Minimal change disease (lipoid nephrosis) (4) Amyloidosis (5) Membrano-proliferative glomerulonephritis (MPGN) (Note: MPGN may be classified as both nephrotic and nephritic syndromes) (6) Diabetic glomerulonephropathy
What are the 5 glomerular diseases that are primarily classified as nephritic syndromes?
(1) Acute poststreptococcal glomerulonephritis (2) Rapidly progressive (crescentic) glomerulonephritis (RPGN) (3) Diffusive proliferative glomerulonephritis (DPGN) (Note: Diffusive proliferative glomerulonephritis may be classified as both nephrotic and nephritic syndrome) (4) Berger’s disease (IgA nephropathy) (5) Alport syndrome
What is the most common cause of nephrotic syndrome in adults? What is the second most common cause of primary nephrotic syndrome in adults?
Focal segmental glomerulosclerosis; Membranous nephropathy
What are 5 conditions/factors with which focal segmental glomerulosclerosis is associated?
Associated with (1) HIV infection, (2) Heroin abuse, (3) Massive obesity, (4) Interferon treatment, and (5) Chronic kidney disease due to congenital absence or surgical removal.
Again, what is the second most common cause of primary nephrotic syndrome in adults?
Membranous nephropathy
What factors can cause membranous nephropathy?
Can be idiopathic or caused by drugs (e.g., NSAIDs, penicillamine), infections (e.g., HBC, HCV), SLE, solid tumors.
What is loss in minimal change disease (lipid nephrosis), what is not loss, and why?
Selective loss of album, not globulins, caused by GBM polyanion loss
What might trigger minimal change disease (lipid nephrosis)?
May be triggered by a recent infection, immunization, or an immune stimulus.
In what patient population is minimal change disease (lipid nephrosis) most common?
Most common in children.
What is important to know about the response of minimal change disease (lipid nephrosis) to steroid therapy?
Excellent response to corticosteroids.
With what conditions is amyloidosis associated?
Associated with chronic conditions (e.g., multiple myeloma, TB, RA).
What are the types of membranoproliferative glomerulonephritis (MPGN)? What characteristics distinguish them?
TYPE I - subendotheial IC (immune complex) deposits with granular IF; “tram-track” appearance due to GBM splitting caused by mesangial in growth; TYPE II - intermembranous IC deposits; “dense deposits”
Which type of membranoproliferative glomerulonephritis (MPGN) is associated with “tram-track” appeaerance? What causes this appearance?
TYPE I - subendotheial IC deposits with granular IF; “tram-track” appearance due to GBM splitting
Which type of MPGN is associated with “dense deposits”?
TYPE II - intermembranous IC deposits; “dense deposits”
Among other types of nephrotic syndrome, what is unique about the presentation of MPGN?
(In addition to presenting as nephrotic syndrome) Can also present as nephritic syndrome
With what pathogens is Type I MPGN associated? What is another etiology to consider for Type 1 MPGN?
Type I is associated with HBV, HCV; May also be idiopathic
With what substance is Type II MPGN associated? What role does this substance play?
Type II is associated with C3 nephritic factor (stabilizes C3 convertase –> decrease serum C3 levels)
What effects does nonenzymatic glycosylation (NEG) have in diabetic glomerulonephropathy?
(1) Nonenzymatic glycosylation (NEG) of GBM –> increased permeability, thickening; (2) NEG of efferent arterioles –> increased GFR –> mesangial expansion
What characterizes nephritic syndrome and its presentation?
NephrItic syndrome = an Inflammatory process. When it involves glomeruli, it leads to hematuria and RBC casts in urine.
With what signs/symptoms is nephritic syndrome associated?
Associated with azotemia, oliguira, hypertension (due to salt retention), and proteinuria (<3.5 g/day)
What characterizes acute poststreptococcal glomerulonephritis on light microscopy? What characterizes it on electron microscopy?
LM - glomeruli enlarged and hypercellular; EM - subepithelial immune complex (IC) humps
What characterizes acute poststreptococcal glomerulonephritis upon immunofluorescence, and what causes this?
IF - (“starry sky”) Granular appearance (“lumpy-bumpy”) due to IgG, IgM, and C3 deposition along GBM and mesangium
In what patient population is acute poststreptococcal glomerulonephritis seen?
Most frequently seen in children
What are 3 signs associated with acute poststreptococcal glomerulonephritis presentation?
(1) Peripheral and periorbital edema, (2) Dark urine (cola-colored), and (3) Hypertension
How is acute poststreptococcal glomerulonephritis resolved?
Resolves spontaneously
What characterizes rapidly progressive glomerulonephritis (RPGN) on light microscopy and electron microscopy?
LM and IF - crescent-moon shape
In what glomerular disease are crescents found? What do crescents consist of?
Rapidly progressive (crescentic) glomerulonephritis (RPGN); Crescents consist of fibrin and plasma proteins (e.g., C3b) with gomerular parietal cells, monocytes, and macrophages
What is the prognosis associated with RPGN, and why?
Poor prognosis. Rapidly deteriorating renal functions (days to weeks)
What are 3 disease processes that may result in the pattern of RPGN?
(1) Goodpasture’s syndrome (2) Granulomatosis with polyangitis (Wegener’s) (3) Microscopic polyangitis
What kind of hypersensitivity is Goodpasture’s syndrome?
Type II hypersensitivity
What kind of immunofluorescence is seen in Goodpasture’s syndrome, and what causes this?
Antibodies to GBM and alveolar basement membrane –> linear IF
Again, what are the 3 disease processes that may result in the pattern of RPGN? What is used to make a diagnosis in each case?
(1) Goodpasture’s syndrome - Hematuria/hemoptysis (2) Granulomatosis with polyangitis (Wegener’s) - PR3-ANCA/c-ANCA (3) Microscopy polyangitis - MPO-ANCA/p-ANCA
What 2 things cause diffuse proliferative glomerulonephritis (DPGN)?
Due to (1) SLE or (2) MPGN.
What characterizes diffuse proliferative glomerulonephritis (DPGN) on light and electron microscopy? What characterizes it upon immunofluorescence?
LM - “wire looping” of capillaries; EM - subendothelial and sometimes intramembranous IgG-based ICs often with C3 deposition; IF - granular
What is the most common cause of death in SLE?
Diffuse proliferative glomerulonephritis (DPGN)
What is unique about the presentation of DPGN and MPGN?
DPGN and MPGN can present as nephrotic syndrome and nephritic syndrome concurrently.
To what other condition is Berger’s disease (IgA nephropathy) associated?
Related to Henoch-Schonlein purpura
What kind of nephropathy is Berger’s disease?
IgA nephropathy
What characterizes Berger’s disease on light microscopy, electron microscopy, and immunofluorescence?
LM - mesangial proliferation; EM - mesangial IC deposits; IF - Ig-A based IC deposits in mesangium
What 2 conditions often causes Berger’s disease to present/flare? What clinical/lab findings are associated with Berger’s disease?
Often presents/flares with a URI or acute gastroenteritis; Episodic hematuria with RBC casts.
What mutation causes Alport syndrome? What is the effect of this mutation?
Mutation in type IV collagen –> thinning and splitting of the glomerular basement membrane.
What mode of inheritance is associated with Alport syndrome?
Most commonly X-linked
What are 3 symptoms associated with Alport syndrome? Which of these is less common?
(1) Glomerulonephritis, (2) Deafness, and, less common, (3) Eye problems
What is the most common cause of nephrotic syndrome in African Americans and Hispanics?
Focal segmental glomerulosclerosis is the most common cause of nephrotic syndrome in African Americans and Hispanics
What is important to know about the response of FSGS to steroid therapy?
Inconsistent response to steroid therapy and may progress to chronic renal disease
What is the most common cause of primary nephrotic syndrome in Caucasian adults?
Membranous nephropathy is the most common cause of primary nephrotic syndrome in Caucasian adults
What is important to know about the response of membranous nephropathy to steroid therapy?
Poor response to steroid therapy and may progress to chronic renal disease.
With what condition may minimal change disease (lipoid nephrosis) be associated?
May be associated with Hodgkin lymphoma (e.g., cytokine-mediated damage).
What is the organ most commonly involved in amyloidosis?
Kidney is the most commonly involved organ (systemic amyloidosis).
When does acute poststreptococcal glomerulonephritis typically occur?
Occurs ~ 2 weeks after group A streptococcal infection of the pharynx or skin.
What type of hypersensitivity reaction is acute poststreptococcal glomerulonephritis?
Type III hypersensitivity reaction.
What main 2 lab values are associated with acute poststreptococcal glomerulonephritis?
(1) Increased anti-DNase B titers and (2) Decreased complement levels
Which nephritis would you consider in a patient with episodic hematuria with RBC casts?
IgA nephropathy (Berger disease)
