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
which of these will NOT present with hypocomplementemia?
a. post-streptococcal nephritis
b. IgA nephropathy
c. diffuse proliferative glomerulonephritis (DPGN)
b. IgA nephropathy (nephritis): IgA immune complexes in mesangium, complement activated but not depleted (only IgA deposits)
a. post streptococcal nephritis and c. DPGN (type IV renal SLE) lead to hypocomplementemia following complement fixation (deposit with antibodies in glomerulus)
how does rapidly progressive glomerulonephritis (RPGN) develop? is it nephrotic or nephritic?
RPGN: severe form of glomerulonephritis, crescents form by inflammation (monocytes/macrophages/fibrin)
rapid onset with progressive loss of renal function (often presents as acute renal failure)
Type I (linear IF), II (granular IF), or III (negative IF)
what is the cause and presentation of Type I RPGN (rapidly progressive glomerulonephritis)?
RPGN: severe form of glomerulonephritis, crescents form by inflammation
Type I (linear): antibodies against glomerular basement membrane (Type II hypersensitivity) cause linear pattern of IgG antibodies on immunofluorescence
what type of hypersensitivity reaction is Type I RPGN?
RPGN (rapidly progressive glomerulonephritis): severe form of nephritis, crescents form by inflammation
Type I (linear): antibodies against glomerular basement membrane (Type II hypersensitivity) cause linear pattern of IgG antibodies on immunofluorescence
what type of rapidly progressive glomerulonephritis (RPGN) is Goodpasture’s Syndrome?
Goodpasture’s Syndrome: antibodies to alpha-3 chain of type IV collagen (found in GBM and alveoli)
—>
Type I RPGN (linear): antibodies against glomerular basement membrane (Type II hypersensitivity) cause linear pattern of IgG antibodies on immunofluorescence
what is the cause and presentation of Type II RPGN (rapidly progressive glomerulonephritis)?
RPGN (rapidly progressive glomerulonephritis): severe form of nephritis, crescents form by inflammation
Type II (granular): due to immune complex deposition (Type III hypersensitivity), most often progression of post-streptococcal glomerulonephritis, can also be progression of diffuse proliferative glomerulonephritis (SLE)
what type of hypersensitivity reaction is Type II RPGN?
RPGN (rapidly progressive glomerulonephritis): severe form of nephritis, crescents form by inflammation
Type II (granular): due to immune complex deposition (Type III hypersensitivity)
most often progression of post-streptococcal glomerulonephritis, can also be progression of diffuse proliferative glomerulonephritis (SLE)
post-streptococcal glomerulonephritis can progress to what type of RPGN (rapidly progressive glomerulonephritis)?
post-streptococcal nephritic syndrome: 2-3 weeks following group A beta-hemolytic strep infection
can progress to —>
Type II (granular) RPGN (rapidly progressive glomerulonephritis): immune complex deposition (Type III hypersensitivity)
*most common cause of RPGN
diffuse proliferative glomerulonephritis (DPGN, most common type of renal SLE disease) can progress to what type of RPGN (rapidly progressive glomerulonephritis)?
DPGN: Type IV systemic lupus erythematous (SLE), subendothelial immune complex deposition in glomeruli, thickened capillary loops
can progress to —>
Type II (granular) RPGN (rapidly progressive glomerulonephritis): immune complex deposition (Type III hypersensitivity)
what is the cause and presentation of Type III RPGN (rapidly progressive glomerulonephritis)?
RPGN (rapidly progressive glomerulonephritis): severe form of nephritis, crescents form by inflammation
Type III: “negative” due to lack of Ig staining (“pauci-immune”), most patients are ANCA positive (anti-neutrophil cytoplasmic antibodies) and have vasculitis syndrome
in Type III (“negative”) RPGN, most patients are ____ positive and have _____ syndrome
RPGN (rapidly progressive glomerulonephritis): severe form of nephritis, crescents form by inflammation
Type III: “negative” due to lack of Ig staining (“pauci-immune”), most patients are ANCA positive (anti-neutrophil cytoplasmic antibodies) and have vasculitis syndrome
Type I vs Type II vs Type III RPGN
RPGN (rapidly progressive glomerulonephritis): severe form of nephritis, crescents form by inflammation
Type I (linear): anti-glomerular basement membrane antibodies, Type II hypersensitivity
Type II (granular): immune complex deposition, Type III hypersensitivity
Type III (negative, “pauci-immune”): ANCA positive (anti-neutrophil cytoplasmic antibodies)
Alport Syndrome
hereditary nephritis; X-linked type IV collagen defect (mutation in alpha-3/4/5 chains)
triad - hematuria, hearing loss, ocular disturbances (chains found renal basement membrane, eye, ear)
what syndrome does this describe?
hereditary nephritis; X-linked type IV collagen defect
triad - hematuria, hearing loss, ocular disturbances
Alport Syndrome
describe the cause/triggers of minimal change disease. is this nephritic or nephrotic?
minimal change disease: effacement (flattening) of foot processes of glomerular podocytes —> loss of anion charge barrier to GBM —> nephrotic syndrome
triggered by cytokines, usually idiopathic but associated with Hodgkin Lymphoma (lots of cytokines produced by RS cells)
can also be triggered by prior viral infection (URI), allergic rxn (bee sting), or recent immunization
minimal change disease
minimal change disease: effacement (flattening) of foot processes of glomerular podocytes —> loss of anion charge barrier to GBM —> nephrotic syndrome
triggered by cytokines
what type of cancer is associated with minimal change disease and why does this make sense?
minimal change disease: effacement of foot processes of glomerular podocytes —> nephrotic syndrome
triggered by cytokines, usually idiopathic but associated with Hodgkin Lymphoma - lots of cytokines produced by Reed Sternberg cells
what is the typical immunological trigger for minimal change disease?
minimal change disease: effacement of foot processes of glomerular podocytes —> loss of anion charge barrier to GBM —> nephrotic syndrome
triggered by cytokines, such as by prior viral infection (URI)
what kind of proteinuria is caused by minimal change disease?
minimal change disease: effacement of foot processes of glomerular podocytes, triggered by cytokines —> nephrotic syndrome
“selective” proteinuria - only albumin in urine (NOT immunoglobin)
Pt is an 8yo presenting to their pediatrician after a bout of viral URI, feeling unwell. Urine analysis shows selective proteinuria (only albumin in urine, not immunoglobins). Biopsy is normal under light microscopy and immunofluorescence. The patient is prescribed steroids and responds well. What is likely going on?
minimal change disease: effacement of foot processes of glomerular podocytes —> nephrotic syndrome
triggered by cytokines, such as by prior viral infection (URI), allergic rxn (bee sting), or recent immunization
favorable prognosis, responds very well to steroids
describe the structural changes that occur in focal segmental glomerulosclerosis (FSGS)
FSGS: podocyte injury —> nephrotic syndrome (severe version of minimal change disease)
—> segmental (only portion of glomeruli) / focal (only some glomeruli)
—> pink/dense collagen deposition (hyalinosis) causes collapse of basement membranes
—> effacement of foot processes
is focal segmental glomerulosclerosis (FSGS) nephritic or nephrotic?
FSGS: podocyte injury —> nephrotic syndrome (severe version of minimal change disease)
—> segmental (only portion of glomeruli) / focal (only some glomeruli)
—> pink/dense collagen deposition (hyalinosis) causes collapse of basement membranes
—> effacement of foot processes
often progresses to chronic renal failure (within 10-20 years), does not respond well to steroids
what conditions are associated with focal segmental glomerulosclerosis (FSGS)? (name a few)
FSGS: podocyte injury/hyalinosis —> nephrotic syndrome (severe version of minimal change disease)
usually idiopathic, but secondary causes include:
- HIV
- sickle cell
- heroin
- obesity
- interferon treatment
- nephron loss (single kidney)
describe what occurs in membranous nephropathy - is this condition nephritic or nephrotic?
membranous nephropathy: thick glomerular basement membrane due to subepithelial granular immune complex deposition (IgG, C3) —> nephrotic syndrome (proteinuria)
what structural changes occur in membranous nephropathy?
membranous nephropathy: subepithelial granular immune complex deposition (IgG, C3) —> nephrotic syndrome (proteinuria)
—> thick glomerular basement membrane (but absence of hypercellularity)
—> “spike and dome” immune deposition on basement membrane
what glomerular disease is the cause of Type V renal SLE disease?
nephrotic membranous nephropathy: type V renal SLE
thick glomerular basement membrane due to subepithelial granular immune complex deposition (IgG, C3) —> nephrotic syndrome (proteinuria)
[recall most lupus renal disease is nephritic]
autoantibodies against which antigen are associated with nephrotic membranous nephropathy?
membranous nephropathy: thick glomerular basement membrane due to subepithelial immune complex deposition (IgG, C3) —> nephrotic syndrome
associated with autoantibodies against phospholipase A2 receptor (PLA2R) expressed on podocytes
what are the classic secondary causes of nephrotic membranous nephropathy?
membranous nephropathy: thick glomerular basement membrane due to subepithelial immune complex deposition (IgG, C3)
secondary causes: tumor, hepatitis, rheumatoid arthritis [it rhymes] - solid tumors, Hep B/C, drugs used to treat RA
does diabetic nephropathy caused nephritic or nephrotic syndrome?
diabetic nephropathy: non-enzymatic glycosylation causes leakage of proteins from glomerular basement membrane —> nephrotic syndrome
long term - sclerosis of glomerulus
does amyloidosis cause nephritic or nephrotic syndrome?
amyloidosis: extracellular buildup of amyloid proteins, kidney is most common involved organ —> nephrotic syndrome
classic biopsy findings: apple-green birefringence and Congo red stain
what occurs in membranoproliferative glomerulonephritis (MPGN)? is it nephritic or nephrotic?
MPGN: thick basement membrane + proliferation of mesangial cells/matrix
can be nephritic or nephrotic! depends on whether proteinuria is in nephrotic range
Type I (more common): subendothelial immune complex deposition
Type II: basement membrane complement deposition
what occurs in Type I membranoproliferative glomerulonephritis (MPGN)?
Type I MPGN: more common, due to subendothelial immune complex deposition
IgG activates complement (C3), deposits trigger mesangial ingrowth - “tram track” appearance on light microscopy
associated with hep B and C
what occurs in Type II membranoproliferative glomerulonephritis (MPGN)?
Type II MPGN: “electron dense” deposits in the basement membrane mediated by complement
C3 convertase nephritic factor (stabilizing antibody) found in most patients [recall C3 activates alternative pathway] —> over activation of complement, hypocomplementemia (low C3)
mostly disease of children, half develop ESRD within 10 years
what antibody is found present in most patients with Type II membranoproliferative glomerulonephritis (MPGN)?
Type II MPGN: “electron dense” deposits in the basement membrane mediated by complement
C3 convertase nephritic factor (stabilizing antibody) found in most patients [recall C3 activates alternative pathway] —> over activation of complement, hypocomplementemia (low C3)
which patients are most often affected by Type II membranoproliferative glomerulonephritis (MPGN)? what is the prognosis?
Type II MPGN: “electron dense” deposits in the basement membrane mediated by complement
C3 convertase nephritic factor (stabilizing antibody) found in most patients
mostly disease of children, half develop ESRD within 10 years
Type I vs Type II membranoproliferative glomerulonephritis (MPGN)
MPGN: thick basement membrane + proliferation of mesangial cells/matrix
Type I: subendothelial immune complex, “tram track” appearance, associated with hepatitis B/C
Type II: complement (C3) deposition within basement membrane, mostly disease of children
