NephrOtic/Nephritic Syndromes PATHOMA/FA Flashcards
What is the main characteristic of NEPHROTIC glomerular disorders?
PROTEINURIA - Protein in urine >3.5g/day
Name the 3 proteins that are particularly LOW in NEPHROTIC SYNDROMES and the results.
- HYPOALBUMINEMIA -> Decreased intravascular oncotic pressure -> PITTING EDEMA
- HYPOGAMMAGLOBULINEMIA -> Increased risk of INFECTION
- Decreased ANTITHROMBIN III -> HYPERCOAGULABLE STATE
What molecules are particularly elevated in pts with NEPHROTIC SYNDROMES? As a result, what can be seen in the urine?
HYPERLIPIDEMIA + HYPERCHOLESTEROLEMIA - ‘Blood loses lots of protein, liver responds by throwing out fats to try to beef up the blood’
RESULT: FATTY CASTS in urine
What is the most common cause of NEPHROTIC SYNDROME in children?
MINIMAL CHANGE DISEASE
What syndrome/disease is MINIMAL CHANGE DISEASE (MCD) particularly associated with?
HODGKIN LYMPHOMA
What layer of the glomerular filtration barrier is effaced (Flattened) in MCD?
FOOT PROCESSES OF PODOCYTES (i.e. EPITHELIAL CELLS)
IMAGING of MINIMAL CHANGE DISEASE: What do you see on H&E, EM, and IF?
H&E: Normal glomerulus
EM: Flattened (effaced) foot processes
IF: NEGATIVE (no immune complex deposits)
Which NEPHROTIC SYNDROME is the only one that responds EXCELLENTLY to steroids? Why?
MCD
Because effaced podocytes in MCD result from a high [cytokine] whether it’s idiopathic or from Hodgkin’s lymphoma
Steroids = Less cytokine production
Which proteins are lost in MINIMAL CHANGE DISEASE?
ONLY ALBUMIN
‘Think of it as MCD is so minimal that only albumin is lost’
Are NEPHROTIC syndromes generally familial/genetic, environmental, or idiopathic? Do they generally respond well to STEROID therapy?
IDIOPATHIC - most common
Do NOT respond well to steroids - except for MCD
Which is the most common cause of NEPHROTIC SYNDROME in Hispanics and African Americans?
FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)
Which pt populations are most likely to have FSGS, if they have a NEPHROTIC SYNDROME?
- HIV
- Heroine usage
- Sickle cell disease
What is the imaging seen on FSGS? Include H&E, EM, and IF
H&E: Segmental + focal Sclerosis (dense pink collagen deposits) in glomeruli
EM and IF - same as MCD bec it is almost a progression of MCD that was unresponsive to steroids [Effaced foot processes, negative IF]
What is the most common cause of NEPHROTIC SYNDROME in Caucasian adults?
MEMBRANOUS NEPHROPATHY
What is the most common cause of death in SLE pts? What is the most common specific disease responsible for it?
RENAL FAILURE - Specifically Diffuse Proliferative Glomerulonephritis
If a SLE pt had proteinuria >3.5g/day, pitting edema (hypoalbuminemia), increased risk of infection (hypogammaglobulinemia), hypercholesterolemia, and clots very easily, what particular disease is this pt most likely suffering through?
Pt has NEPHROTIC SYNDROME - most common renal nephrotic disease in SLE pt is MEMBRANOUS NEPHROPATHY
What are the non-idiopathic associations of MEMBRANOUS NEPHROPATHY?
HEPATITIS B/C + Solid tumors + SLE + Drugs (NSAIDS, PENICILLINAMINE)
What is the ddx (renal pathology) when Immunofluorescence is GRANULAR?
GRANULAR IF = IMMUNE COMPLEX DEPOSITS
Ddx: NEPHROTIC (2): Membranous Nephropathy + Membranoproliferative Glomerulonephritis
NEPHRITIC (all)
What two disorders have thickened glomerular membranes due to immune complex depositions?
Renal disorders that have “membranous” - MEMBRANOUS NEPHROPATHY + MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
SPIKE and DOME appearance on EM: What renal disease am I?
MEMBRANOUS NEPHROPATHY
What is shown on imaging of MEMBRANOUS NEPHROPATHY? List H&E, EM, and IF.
H&E: Thickened glomerular membranes
EM: Spike and dome - subepthelial deposits
IF: Granular IF - immune complex
Which nephrotic syndrome is MOST commonly associated with TRAM TRACK appearance on H&E stain?
TYPE I (SUBENDOTHELIAL) MPGN
What is the imaging results of MPGN? List HE, EM, and IF.
H&E and EM: Thickened capillary membrane with TRAM TRACK (more common with Type I MPGN)
IF: Granular due to immune complex deposits
What is the proliferative component of MPGN?
MESANGIAL CELLS proliferate their cytoplasm -> Cuts into the immune complex deposit -> TRAM TRACKS
What diseases is TYPE I MPGN most associated with?
HBV and HCV
What condition is TYPE 2 MPGN most associated with?
Associated with C3 NEPHRITIC FACTOR - which stabilizes C3 CONVERTASE -> LOW C3 + HIGH C3a/C3b -> Complement overactivation -> Glomerular damage
What is unique of MPGN in terms of classification: NephrOtic, NephrItic?
MPGN can be Nephrotic, Nephritic (moreso Type II MPGN - inflammation related), or BOTH
What are the two causes of HYALINE ARTERIOSCLEROSIS?
- BENIGN HTN
2. DIABETES MELLITUS: Nonenzymatic glycosylation of vascular BM -> Protein leakage into BV wall -> HA
What is the first change to the kidney seen in DIABETES MELLITUS?
Non-enzymatic glycosylation of the vascular membrane -> HYALINE ARTERIOSCLEROSIS
Where does DM-mediated HYALINE ARTERIOSCLEROSIS preferentially occur?
EFFERENT ARTERIOLE
What happens as a result of EFFERENT ARTERIOLE HYALINE ARTERIOSCLEROSIS seen in a diabetic kidney?
INCREASE in GFR -> Hyperfiltration-induced damage -> MICROALBUMINURIA
In late-stage DM, what renal syndrome is developed in the kidney? What is the pathogenesis?
NEPHROTIC SYNDROME develops after mesangial sclerosis
KIMMELSTIEL-WILSON NODULES are pathognomonic of __? What are these nodules?
DIABETES MELLITUS
Nodules that contain significant MESANGIAL SCLEROSIS
What treatment can slow the progression of Hyperfiltration-induced glomerular damage of a pt with DIABETES MELLITUS? How?
ACE INHIBITORS - Block AngII’s efferent arteriolar vasoconstriction that would also INCREASE GFR and cause hyperfiltration
What is the most commonly involved organ in SYSTEMIC AMYLOIDOSIS? How specifically does amyloidosis affect this organ?
KIDNEY - Amyloid deposits in the MESANGIUM -> Nephrotic syndrome
What is the confirmatory test of SYSTEMIC AMYLOIDOSIS?
CONGO RED STAIN: Apple-green birefringence under polarized light
What is the most common cause of END-STAGE RENAL DISEASE in the US?
DIABETIC GLOMERULONEPHROPATHY
What are characteristics of the urine in NEPHRITIC SYNDROME?
- LIMITED proteinuria (
What are the most prototypical Sx of NEPHRITIC SYNDROME?
PERIORBITAL EDEMA + HTN - due to salt and secondary water retention
Minimal edema presents in the loose CT around the eyes
What does a biopsy of NEPHRITIC SYNDROME glomerulus look like?
HYPERCELLULAR, INFLAMED glomeruli due to:
Immune complex deposition -> Activates complement -> C5a attracts neutrophils (hypercellular)
SUBEPITHELIAL HUMPS on EM = ____?
POST-STREP GLOMERULONEPHRITIS (PSGN)
What are the imaging results of PSGN. List HE, EM, IF.
HE: Hypercellular, inflamed glomeruli
EM: SUBEPITHELIAL DEPOSITS (Immune complex deposits that originated SUBENDOTHELIAL travel up above BM)
IF: Granular
What infection elicits PSGN?
- GROUP A beta-hemolytic STREPTOCCOCAL infection of the pharynx or skin (impetigo) - nephritogenic strain containing M protein (virulence factor)
- NON-STREPTOCOCCAL infection
What is the treatment of PSGN? What is the basis for this treatment?
SUPPORTIVE - Only supportive because the SUBEPITHELIAL complex deposits eventually dissipate out and disappear
What is the most common age population of PSGN?
Children
What is the difference in terms of potential complications of PSGN in CHILDREN and ADULTS?
More common pt pool: Children - Only 1% can progress to RENAL FAILURE
Adults - 25% can progress to RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS
What is the distinguishing clinical sign when comparing RPGN of GOODPASTURE vs. WEGENER GRANULOMATOSIS? What is the distinguishing IF imaging pattern?
GOODPASTURE: IF is LINEAR (auto-Ab against collagen on alveolar and glomerular membranes) + NO NASOPHARYNX involvement
WEGENER: IF is NEGATIVE, so ANCA test is done and shows c-ANCA + YES NASOPHARYNX involvement (sinusitis/history of sinus infections)
What is seen on HE imaging of RPGN? What is this particular feature made up of?
CRESCENT in Bowman’s space = Inflammatory debris = FIBRIN + MACROPHAGES
Pt with RPGN has an IF result of SHARP, LINEAR. What disease does pt have?
GOODPASTURE - Auto-Ab against collagen in alveolar and glomerular BM
Pt with RPGN has a NEGATIVE IF. What is on my Ddx now? What test does pt now need to get?
Ddx: Wegener granulomatosis, Microscopic Polyangiitis, and Churg-Strauss Sydnrome
Pt needs to get ANCA test
What is an ANCA test? What are the two possible results? What RPGN disease are associated with each?
Anti-neutrophil cytoplasmic Antibody test
- c-ANCA (cytoplasmic) = Wegener Granulomatosis
- p-ANCA (perinuclear) = Microscopic Polyangiitis + Churg Strauss Syndrome
How do you distinguish CHURG-STRAUSS SYNDROME from MICROSCOPIC POLYANGIITIS as two probable causes of RPGN with a p-ANCA IF result?
CHURG-STRAUSS has 3 features that are ABSENT in microscopic polyangiitis: GRANULOMATOUS INFLAMMATION + EOSINOPHILIA + ASTHMA
Pt has RBC casts in the urine, oliguria, proteinuria
Pt has NEPHRITIC Syndrome, not Nephrotic
Ddx: PSGN + DPGN (diffuse proliferative glomerulonephritis)
In a pt with NEPHRITIC SYNDROME and GRANULAR IF, what is the most common/probable disease that the pt has?
PSGN - POST STREPTOCOCCAL GLOMERULONEPHRITIS
In a SLE pt with NEPHRITIC SYNDROME and GRANULAR IF, what is the most common/probable disease that the pt has?
DPGN - DIFFUSE PROLIFERATIVE GLOMERULONEPHRITIS
Which is the one renal disease with IgA complex deposition?
BERGER DISEASE - IgA NEPHROPATHY
What is the most common nephropathy worldwide?
IgA NEPHROPATHY (BERGER DISEASE)
What is the most common cause of BERGER DISEASE? Explains the pathogenesis.
MUCOSAL INFECTIONS -> Excessive IgA production -> IgA deposits in MESANGIUM of glomeruli
Why is the HEMATURIA seen in BERGER DISEASE (IgA NEPHROPATHY) episodic?
Bec Berger Disease is elicited by IgA complexes, and you get IgA with episodic mucosal infections. When infection subsides, IgA disappears
ALPORT SYNDROME is a defect in what molecule? Is ALPORT sporadic or inherited? If inherited, what is the inheritance pattern?
Defect in TYPE 4 COLLAGEN
INHERITED - X-linked
What are the 3 clinical Sx of ALPORT SYNDROME based on the thinning and splitting of basement membranes?
SENSORY HEARING LOSS + OCULAR DISTURBANCES + ISOLATED HEMATURIA (BM of glomeruli and ocular system)
What are the 4 NEPHRITIC SYNDROMES of the kidney?
‘2 + 2 names’
- POST-STREPTOCOCCAL GLOMERULONEPHRITIS (PSGN)
- RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS (RPGN)
- BERGER DISEASE (IgA nephropathy)
- ALPORT SYNDROME
What type of immune reaction is exhibited in ACUTE PSGN? (post-streptococcal glomerulonephritis)
TYPE III HSR
What type of immune complexes are seen in PSGN and where are they located?
IgG, IgM, and C3 deposits along MESANGIUM and GBM
What is the most common AutoAg of which Abs are produced against in MEMBRANOUS GLOMERULONEPHROPATHY?
Phospholipase A2 Receptor
