GLOMERULONEPHRITIS Flashcards
(46 cards)
Normal interstitium?
NORMALLY, there should be VERY LITTLE visible interstitium –> in chronic kidney diseases, tubules atrophy so the interstitium becomes FAR more prevalent
What are trichrome stains good for?
Visualizing the INTERSTITIUM
Diffuse, focal, segmental, global
Diffuse = greater than 50% of ALL GLOMERULI are affected
Focal = LESS than 50% of all glomeruli affected
Segmental = only affect a PORTION of EACH glomerulus
Global = All of the glomerulus is affected
Four main presentations of glomerulonephritis?
NEPHRITIC syndrome
NEPHROTIC syndrome
Rapidly Progressive Glomerulonephritis
Asymptomatic Hematuria
Criteria for NEPHRITIC SYNDROME
Mild-moderate proteinuria ( < 3.5 g/day) Oliguria (output < 400 cc/day) HEMATURIA Hypertension Edema
INFLAMMATION of the glomerular tuft
Due to SWELLING of the capillaries, there is DECREASED filtrate entering tubules –> oliguria
The swelling also DAMAGES VESSELS, causing blood and protein to leak into the urine –> PROTEINURIA, HEMATURIA (unique!)
Leakage of blood results in the formation of RBC CASTS
Retention of fluid results in INCREASED HYDROSTATIC PRESSURE in ALL VESSELS OF THE BODY –> EDEMA (oncotic not enough to counteract)
What are the main causes of NEPHRITIC?
DIFFUSE PROLIFERAIVE GLOMERULONEPHRITIS = POST-INFECTIOUS = POST-STREP GLOMERULO!!!!!
IgA Nephropathy (Berger’s) –> MOST COMMON WORLDWIDE
LUPUS NEPHRITIS (can present in every way though)
MEMBRANOPROLIFERATIVE (nephritic AND nephrotic)
Criteria for NEPHROTIC SYNDROME
Not really inflammatory
HALLMARK = HEAVY PROTEINURIA ( > 3.5g/day) and NO HEMATURIA
The proteinuria leads to HYPOALBUMINEMIA –> results in edema due to LACK OF ONCOTIC PRESSURE IN VASCULAR SPACE –> fluid rushes out of vessels (unopposed hydrostatic) –> SO, piss out a ton of protein, lose oncotic pressure, hydrostatic pushes fluid out –> EDEMA
HYPERLIPIDEMIA (liver compensates for low protein by cranking out more protein –> Apolipoprotein –> cholesterol increases!)
Again, HEAVY PROTEINURIA, EDEMA, HYPERLIPIDEMIA and NO HEMATURIA!
What are the typical causes of NEPHROTIC?
MM FAN (or MM FAD)
M - Membranous glomerulonephropathy
M - Miniminal Change DIsease
F = Focal Segmental GlomeruloSCLEROSIS A = Amyloidosis N/D = Nodular Sclerosis (via Diabetes)
And LUPUS which can cause everything
RAPIDLY PROGRESSING GLOMERULONEPHRITIS
Bad news!!! Renal function deteriorates RAPIDLY
50% of renal function will be lost within a 3 month period –> most other disorders are less progressive and take a long time to develop
HALLMARK = CRESCENT FORMATION!!!!!!! Can be named Crescentic Glomerulonephritis
Presents with RAPID destruction –> Nephritic with RED CELL CASTS
Crescent forms due to PROLIFERATION of the PARIETAL EPITHELIUM that line’s Bowman’s Capsule –> BM of the capsule prevents epithelium from growing outwards, so they have no choice but to grow towards the capillary tuft –> EVENTUALLY CAUSES THE TUFT TO SHRINK AND BECOME DAMAGED
What are the 3 types of Crescentic/RPGN?
Type 1 = GOODPASTURES SYNDROME = A disease of the LUNGS AND KIDNEYS!!!! Interstitial vessels of the lung and BM of the glomerulus are involved, causing HEMOPTYSIS (cough blood) and HEMATURIA/NEPHRITIC SYNDROME
Autoantibodies target the BM for the renal aspect –> there is a LINEAR STRING OF FLUORESCENCE (instead of granular)
Type 2 = A “hodgepodge” of all immune complex glomerulonephritities –> causes include DPGN, MPGN IgA, Lupus
Type 3 = ANCA associated –> Associated with POLYARTERITIS NODOSA, WEGENER’S –> NO IMMUNE COMPLEXES!!!!!!
Asymptomatic Hematuria
The fourth presentation –> Typically seen in YOUNG PATIENTS
Feel healthy, but RBCs end up in the urine
Prototype disease for this is IgA NEPHROPATHY –> deposition of IgA within the glomerulus
Kidney RETAINS NORMAL FUNCTION
What are the three cell types that swell in glomerulonephritis?
ENDOTHELIAL – Blood Vessels
EPITHELIAL – Podocytes (also called VISCERAL EPITHELIUM)
MESANGIAL
Types of DEPOSITS
SubEPIthelial –> Associated with LUPUS (all of them), POST-INFECTIOUS (which is DPGN and Nephritic), and MEMBRANOUS GLOMERULONEPHRITIS (nephrotic)
SubENDOthelial –> MEMBRANOUS PROLIFERATIVE (nephritic)
WIthin the MESANGIUM –> IgA NEPHROPATHY likely
MINIMAL CHANGE DISEASE
NEPHROTIC
FUSED or OBLITERATED podocyte foot processes –> NO IMMUNE DEPOSITS!
Usually a disease of CHILDREN; Associated with HODGKINS in ADULTS –> night sweats, weight loss, lymphadenopathy
Flattening of foot processes, diffuse effacement, seen on EM
STEROID SENSITIVE
May progress to FSGS
FOCAL SEGMENTAL GLOMERULOSCLEROSIS
Focal = < 50% of glomeruli involved Segmental = only part of each glomerulus Sclerosis = Fibrosis of the mesangial matrix
NO IMMUNE COMPLEXES –> but, WILL see C3 and IgM on immunofluorescence
Patients in 2nd or 3rd decade, OFTEN PROGRESSES FROM MCD
**SECONDARY TO AIDS*** or heroin abuse or Sickle Cell
LM –> Trichrome shows FIBROSIS (blue) and SEGMENTALIZATION (not all of glomerulus affected)
WORSE than MCD –> steroids less successful –> AWFUL prognosis
40%!!!! Progress to ESRD within 10 years
HIGH rate of RECURRENCE in renal transplants
MEMBRANOUS GLOMERULONEPHROPATHY
NEPHROTIC
BM involved –> thickened with small, evenly spaced SUBEPITHELIAL deposits
Middle aged, ASSOCIATED WITH MALIGNANCY
Secondaryily from LUPUS, HEP B/C, Malignancy and NSAIDs
LM –> diffusely thickened capillary loop, normal cellularity, SPIKES on the membrane(?)
FINELY GRANULAR DEPOSITS OF IgG and C3 on IMMUNOFLUORESCENCE
EM –> REMARKABLY THICKENED BM; SUBEPITHELIAL DEPOSITS; Lack of “humps” so it’s not DPGN
Prognosis –> Steroids don’t do shit and this will PROBABLY PROGRESS TO ESRD
MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
BOTH NEPHRITIC/NEPHROTIC
MESANGIAL cell PROLIFERATION
Thickened BM
“Tram Track” appearance
YOUNG and MIDDLE-AGED
Proteinuria is primary finding, but proliferative causes HEMATURIA as well!!!! (anytime we have proliferation, RBCs, RBC casts, hematuria)
Primarily idiopathic (like the others), secondarily by INFECTION, ENDOCARDITIS, AUTOIMMUNE, HEPATITIS
Two types
Type I MPGN
Similar on LM and immunofluorescence
Classical COMPLEMENT PATHWAY IMMUNE COMPLEXES
Type II MPGN
Involves C3 NEPHRITIC FACTOR (alternate complement pathway)
AUTOANTIBODY – inhibits the enzymes that stop the alternate pathway (constant activation)
SUBENDOTHELIAL DEPOSITS
Imaging of MPGN
Lots of CELLULARITY (proliferative!)
TRAM TRACK APPEARANCE of BM
Effacement of FOOT PROCESSES
SUBENDOTHELIAL deposits
Type II has SAUSAGE-LINK DEPOSITS on EM, linked by a thin BM
What leads to Asymptomatic Hematuria (usually?)
IgA NEPHROPATHY
Presentation of IgA Nephropathy
IgA Mesangial Deposition – normal capillary walls, normal BM - ONLY mesangium affected
Presents as ASYMPTOMATIC HEMATURIA –> high serum IgA –> Chronic, progressive course
Primarily idiopathic, secondary to LUPUS, IgA disease
LOTS of IgA seen in immunofluorescence
Imaging –> INCREASE CELLULARITY in mesangium, IgA immunofluorescence, Lots of cells on EM
MOST COMMON GLOMERULONEPHRITIS WORLDWIDE!!!!!!! High recurrence in transplants
LIKELY TO PROGRESS TO ESRD!!!!!!!!!!!
LUPUS NEPHROPATHY
Can present in any way we discussed –> NEPHRITIC, NEPHROTIC, HEMATURIA
Glomerular IMMUNE DEPOSITS!!!!!!!! Classic LUPUS AUTOANTIBODIES ANA, APA
Six classes from WHO
I - Minimal mesangial
II - Mesangial proliferative
III - Focal Proliferative (mesangial prolif, sclerotic deposits, less than 50% glomeruli)
IV - Diffuse Proliferative
V - Membranous - thickened GBM, may combine with other classes
VI - ADVANCED SCLEROTIC –> 90% of glomeruli globally sclerotic without fxn
Diabetes and Nephropathy
NODULAR SCLEROSING!!!!!!!!
This is a NEPHROTIC syndrome (high protein)
MOST COMMON CAUSE OF ESRD
Mesangial expansion, GBM thickened, vascular intimal thickening, NODULAR GLOMERULOSCLEROSIS = KIMMESTEIL WILSON LESIONS*
NO IMMUNE DEPOSITS
PAS +