Glomerulonephritis B&B Flashcards
which proteins cause the basement membrane of the glomerular filtration barrier to be negatively charged?
- Type IV collagen
- heparan sulfate
repels (-) molecules like albumin
How does glomerular bleeding usually appear in the urine?
red cells casts (generally not clots - too big), acanthocytes (dysmorphic RBC), red/smoky brown/“coca cola” color
What systemic effects are caused by nephrotic syndrome?
nephrotic syndrome: filtration barrier to proteins lost, but RBC filtration barrier is intact
proteinurea triggers cascade is pathology:
—> low immunoglobins cause infection
—> low albumin increases liver activity, causing hyperlipidemia
—> low albumin decreases oncotic pressure, causing edema
—> low ATIII causes thrombosis
what occurs in nephrotic syndrome?
nephrotic syndrome: filtration barrier to proteins lost, but RBC filtration barrier is intact
proteinurea triggers cascade is pathology:
—> low immunoglobins cause infection
—> low albumin increases liver activity, causing hyperlipidemia
—> low albumin decreases oncotic pressure, causing edema
—> low ATIII causes thrombosis
how does urine in nephrotic syndrome appear?
nephrotic syndrome: filtration barrier to proteins lost, but RBC filtration barrier is intact
—> massive proteinuria
—> hyperlipidemia (low albumin triggers liver activity) - fatty casts or oval fat bodies
how do urine samples appear in nephrotic vs nephritic syndrome?
nephrotic syndrome (protein barrier lost): massive proteinuria, hyperlipidemia (increased liver activity)
nephritic syndrome (protein and RBC barrier lost - renal failure): RBC casts, mild proteinuria
Pt is a 31yo F presenting to their GP for complaints of a suspected allergic reaction. PE notes swollen ankles and periorbital swelling. Labs reveal high serum cholesterol (>300mg/dL), frothy urine, and proteinuria (>3.5g/day). What is likely going on?
nephrotic syndrome: filtration barrier to proteins lost, but RBC filtration barrier is intact
—> massive proteinuria
—> hyperlipidemia (low albumin triggers liver activity) - fatty casts or oval fat bodies
nephrotic syndrome often mistaken for allergic rxn
what occurs in nephritic syndrome?
nephritic syndrome: inflammatory process damages entire glomeruli, filtration barrier to RBCs and protein is lost —> decreased GFR
—> dysmorphic RBC in urine, RBC casts
—> proteinuria (less than nephrotic syndrome due to lower GFR)
What are the systemic effects of nephritic syndrome?
nephritic syndrome: inflammatory process damages entire glomeruli, filtration barrier to RBCs and protein is lost —> decreased GFR —>
—> increased BUN/Cr
—> increased hydrostatic pressure causes HTN and edema
—> oliguria
On rounds, you encounter a patient with generalized swelling and fatigue complaining of dark urine. Lab workup reveals mild proteinuria. What is the likely diagnosis?
nephritic syndrome: inflammatory process damages entire glomeruli, filtration barrier to RBCs and protein is lost —> decreased GFR —>
—> increased BUN/Cr
—> increased hydrostatic pressure causes HTN and edema
—> oliguria
—> dysmorphic RBC + casts in urine (dark urine)
where is the site of glomerular injury in nephritic vs nephrotic syndrome and why does this make sense?
nephrotic: podocyte injury (filtration barrier) —> protein loss only (separated from blood by GBM)
nephritic: endothelial and mesangial cell injury (exposed to blood) —> inflammation (nephritis) —> loss of RBC and protein in urine
describe how post-streptococcal glomerular injury occurs? is it nephritic or nephrotic?
post-streptococcal nephritic syndrome: 2-3 weeks following group A beta-hemolytic strep infection (impetigo, pharyngitis) with nephritogenic strain (specific M protein virulence factor subtype)
—> immune complexes deposit in kidney, fix complement, attract PMNs
—> hypocomplementemia, enlarged/hypercellular glomeruli, sub-epithelial humps (IgG, C3) on electron microscopy
Pt is a 4yo M presenting 3 weeks post strep throat infection. Parent notes the child’s urine has been dark. Labs are done which show RBC and protein in the urine. A kidney biopsy is taken for electron microscopy, which shows enlarged, hypercellular glomeruli with subepithelial humps. What is going on, and what is the prognosis for this patient?
post-streptococcal nephritic syndrome: 2-3 weeks following group A beta-hemolytic strep infection (impetigo, pharyngitis) with nephritogenic strain (specific M protein virulence factor subtype)
—> immune complexes deposit in kidney, fix complement, attract PMNs
—> hypocomplementemia, enlarged/hypercellular glomeruli, sub-epithelial humps (IgG, C3) on electron microscopy
which class of antibodies deposit in the kidneys in post-streptococcal nephritis, and where do they deposit?
subepithelial humps see on electron microscopy
due to IgG, C3 seen on immunofluorescence
which patients are classically affected by post-streptococcal nephritis? what is the prognosis for adults vs children and how is it treated?
more common in children - classically child 2-3 weeks after strep throat infection (due to group A, beta-hemolytic strep of nephritogenic strain)
good prognosis in children (95% recover)
worse prognosis in adults - many develop renal insufficiency, even 10-40 years later
supportive therapy with spontaneous resolution
describe how Berger’s disease occurs? is it nephritic or nephrotic?
Berger’s disease, aka IgA nephropathy: nephritic syndrome with repeated episodes of hematuria over time leading to end-stage renal disease
due to overactive immune system with high IgA synthesis which deposit in mesangium and activate complement (alternative and lectin pathways)
which class of antibodies deposit in the glomerulus in Berger’s disease? where do they deposit?
Berger’s disease, aka IgA nephropathy: nephritic syndrome with repeated episodes of hematuria over time leading to end-stage renal disease
due to overactive immune system with high IgA synthesis which deposit in mesangium and activate complement (alternative and lectin pathways)
which antibodies deposit and where in post-streptococcal nephritis vs Berger’s disease nephritis vs DPGN?
post-streptococcal nephritis: IgG, C3 deposit in subepithelial humps
Berger’s disease, aka IgA nephropathy (nephritis): IgA deposit in mesangium
DPGN (diffuse proliferative glomerulonephritis): “full house” immunofluorescence - IgG, IgA, IgM, C3, C1q, subendothelial deposits
Pt is a 17yo M with PMH of recurrent episodes of hematuria since childhood, following respiratory (URI) or GI (diarrhea) infections. Renal function has been on a steady decline, as noted by increase BUN/Cr levels, and there is concern of ESRD in the next few years. What is likely going on?
Berger’s disease, aka IgA nephropathy: nephritic syndrome with repeated episodes of hematuria over time leading to end-stage renal disease, most common glomerulonephritis
due to overactive immune system with high IgA synthesis which deposit in mesangium and activate complement (alternative and lectin pathways)
triggered days after respiratory, GI infections
how do the following glomerular disorders vary in the timing of their presentation?
a. post-streptococcal nephritis
b. IgA nephropathy
c. minimal change disease
a. post-streptococcal nephritis: weeks after infection (by Group A beta-hemolytic strep)
b. IgA nephropathy: nephritic syndrome days after infection (respiratory, GI)
c. minimal change disease: nephrotic syndrome after URI (respiratory)
Henoch-Schonlein Purpura
IgA nephropathy with extra-renal involvement —> diffuse IgA deposition
—> palpable purpura on butt/legs, GI and joint pain
most common childhood systemic vasculitis
describe how diffuse proliferative glomerulonephritis (DPGN) develops
DPGN: Type IV systemic lupus erythematous (SLE) nephritis, most common subtype of SLE renal disease (I-V types)
due to subendothelial immune complex deposition in glomeruli, triggering inflammatory response —> increased cellularity, PMN infiltration, thickened capillary loops (“wire looping”), “full house” immunofluorescence* (IgG, IgA, IgM, C3, C1q), hypocomplementemia
“diffuse” because 50%+ of glomeruli are affected
often presents with other SLE features (fever, rash, arthritis) and often leads to ESRD
which subtype of SLE renal disease is DPGN? is it nephritic or nephrotic?
diffuse proliferative glomerulonephritis (DPGN): Type IV systemic lupus erythematous (SLE), most common subtype of SLE renal disease (I-V types)
due to subendothelial immune complex deposition in glomeruli (IgG, IgA, IgM, C3, C1q), triggering inflammatory response —> increased cellularity, PMN infiltration, thickened capillary loops (“wire looping”)
often presents with other SLE features (fever, rash, arthritis) and often leads to ESRD
usually nephritic (blood + protein in urine) but can be nephrotic (proteins only)
what renal structural changes occur in diffuse proliferative glomerulonephritis (DPGN)?
DPGN: Type IV systemic lupus erythematous (SLE) nephritis
due to subendothelial immune complex deposition (IgG, IgA, IgM, C3, C1q) in glomeruli, triggering inflammatory response —> increased cellularity, PMN infiltration, thickened capillary loops (“wire looping”)
severe, often leads to ESRD
