L13 and L14 Glomerular Pathologies Flashcards
Describe the barriers in vascular/urinary spaces made by podocytes.
Size barrier - Membrane
Charge Barrier - Slith Diagphragm and matrix negatively charged so proteins like albumin w/ negative charge will not go through them
What are the different Glomerular Syndromes?
Acute Nephritic Syndrome
RPGN
Nephrotic Syndrome
Asymptomatic Hematuria or proteinuria
CRF
What are crescents and how do they form?
Crestents are Extra-capillary proliferations of cells - example of hypercellularity
Made from rupture of peripheral capillary BM and spillage of fibrin / macros into Bowman’s Capsule space
Parietal Epithelial cells proliferate to form crescents!!
Focal vs diffuse?
Segmental vs global?
Focal - means only some glomeruli and not all of them like in diffuse
Ex. Diffuse is Post-Infectious vs Focal which you can miss in biopsy!
Segmental - only parts of each glomerulus and not the whole thing as in global
describe (and give example of) the 3 different patterns of immunofluorescence that you can see.
Lumpy-Bumpy/Granular - ex Membranous Glomerulopathy (spike and dome)
Linear and Smooth - Anti-GBM in Good Pasture’s
Mesangial deposits - IgA Nephropathy
Nephritic Syndrome/Acute Proliferative GN:
Clinical presentation?
Histology?
Associations?
Pathogenesis?
Clinical: Hematuria and RBC casts, Azotemia, Oliguria, Proteinuria (<3.5) and mild to moderate HTN, Edema - face and hands
Ex. Post-Infectious GN
Histology: Hypercellularity - INFLAMMATION!
Associations - Systemic disease OR Primary GN
Pathogenesis - immune complexes
What is the example of Acute Nephritic Syndrome?
Presentation?
Outcomes?
(next flashcard histology)
Post-Infectious GN / Post-Streptococcal GN
- 1-4 weeks after infection of pharynx/skin, usually kids, Group A beta hemolytic strem where you have immune complex Pathogenesis
Clinical - Malaise, Fever, Mild-moderate HTN, Periorbital edema,
- Oliguria, **Hematuria w/ RBC casts and mild Proteinuria (<1g/day) **
- Elevations in Strep Ab titers and decreases in C3 complement
Outcomes:
- Kids - 95% recovery
- Adults - some develop RPGN or chronic GN
What are the histological Identifiers for PSGN?
Diffuse Hyperceullarity that is Inra-Capullary - obliterated capillary lumen/tubules and RBC casts
Sub-Epithelial Dense Deposits = Humps
Lumpy-Bumpy isolated scattered deposits in BM and Mesangium on EM
SEE PCITURE ATTACHED
What is RPGN? How does it present? What exactly happens there?
Rapidly progressive loss of renal function associated w/ Oliguria
Necrosis and Crescent formation
GBM ruptures and blood filled w/ fibrin and other proteins/cells spills into Bowman’s Space and produce glomerular nephrosis –> CRESCENTS!
[see picture]
What are the 3 different classifications of RPGN?
How can you ID the 3 different types?
1) Immune-Complex Mediated: Granular Immune Deposits; ex. SLE and IgA nephropathy or Post-infectious GN
2) Anti-GBM = Linear immune deposits in Good PAsture’s Disease
3) Pauci-Immune associated w/ Vasculitis and ANCA where anti-PMN antibody causes them to rupture/degranulate and that degrades BM
What is Good PAsture’s? How does it present? What happens in it? How do you treat it?
Goodpasture’s = Anti-GBM w/ Linear IF of IgG/C3
Antibodies attach to EACH epitope along membrane
See alveolar destruction of lungs –> Pulmonary hemorrhage as well as RPGN
Treatment: PLasmapharesis + STeroids + CTX
What are causes of Reno-Pulmonary diseases?
Anti-GBM = Goodpasture’s
Wegener’s Granulomatosis - small vessels in kidney and lungs vasculitis + Granulomas
Microscopic Polyangitis
What is Immune-Complex Meidated RPGN? What happens there? What causes this? Testing in this?
Granular Immune Deposits - circulating Ab deposit in random way and attract mediators that degranulate etc.
Seen in SLE, IgA Nephropathy
What is Pauci-Immune GN? What causes it? What do diferent tests show?
Pauci-Immune = no immune deposits = ANCA glomerulonephritis
Has become MOST COMMON cause of crescentic GN
ANCA vasculitis - Antibodies against PMN
- cANCA = cytoplasmic PR3-ANCA
(Wegener’s c-ANCA)
-pANCA = Perinuclear MPO-ANCA
(vasculiits)
p-ANCA can be False Positive in other inflammatory diseases such as IBD, sclerosising cholangitis, RA
What is Nephrotic Syndrome? What causes it in adults and what causes it in kids?
Leaky Glomerulus that leads to MASSIVE Proteinuria (>3.5 g/day), Hypoalbuminemia, EDEMA, Hyperlipidemia, Infections, Thromboembolic Complications
Children <15 yo - Minimal Change Disease
Adults - Membranous GN or FSGS (or from systemic disease like SLe, DM, Amyloid)
Membranous Glomerulopathy - what is it? Who gets it? What characteristics do you see in histology?
Most common caue of NS in adults - diffuse thickening of glomerular walls and accumulation of Ig-deposits on Sub-Epithelial side
85% Idiopathic and 15% due to drugs, tumors, SLE, infections
No hypercellularity but do see thick and rigid membranes and every segment of membrane has deposits (unlike Post-infectious which has random deposits)
Histology: Sub-Epithelial Spikes and Domes
Granular pattern IgG and complement
”'’member when spike got dome” from the land before time
see pic
What is the clinical course for membranous GN?
thicker the BM the worse the proteinuria
insidious onset of nephrotic syndrome w/ variable but generally indolent course
only 20-30% respond to steroids but spontaneous remission can occur
ALWAYS want to rule out secondary membranous GN from lupus or tumors!!
What are the diseases that cause Podocyte Effacement? how can you tell them apart?
Both cause Nephrotic Syndrome through Podocyte Injury and can start w/ MCD and progress to FSGS
Minimal Change Disease - CHILDREN!!! Response to steroids!!!
FSGS - adults and no repsonse to steroids; *Proteinuria is non-selective, often Hematuria, decreased GFR, HTN
What is MCD? Who gets it? What happens? Clinical and outcomes?
Most common cause of NS in children (peak 2-6 yrs)
Dramatic response to steroids!!!
Cuases: cytokine-like substances affecting podocytes
*Effacement of Foot Processes!!!
***EM: only way to tell and see swollen weird podocytes that are de-differentiated and globular (see picture)
Proteinuria is highly selective!!! more albumin and smaller proteins
Good prognosis but complicates NSAID therapy
What is FSGS? What is it associated w? What do you see in histology? Etiology?
FSGS: proteinuria, Glomerulosclerosis, effacement of podocytes
Histology: Sclerosis and Hyalinosis
Epithelial damage and EM shows effaced foot processes
Causes: Primary = Idiopathic
Secondary = scaring from another GN type (IgA or sLE), Reflux Nephropathy, Disproportion between body and renal mass (obesity) or HIV, IVDA, or Sickle Cell disease
What do you see in HIV FSGS?
Collapsing FSGS!!!
tufts implide to center of axis and then abnormal podocytes surrounding
What glomerulopathies are associated w/ Asymptomatic Hematuria/Proteinuria?
IgA nephropathy
Alport Syndrome
Thin Membrane Disease
What is Berger disease? Aka IgA nephropathy? What happens there?
Prominent IgA deposits in mesangium and causes recurrent hematuria - often associated w/ mucosal infections and get sick (like GI or URI) and then get hematuria
Can be caused from systemic IgA disease (Henoch-Schoenlein Purpur) or chronic liver disease - secondary where abnormal metabolism
What is the histology of IgA nephropathy? What is the clinical course?
Histology: Mesangial Expansion w/ increases cells and matrix and IgA deposition there in membrane araes
Clinical course: hematuria and slow progression to chronic renal failure in 50% patients
no specific treatment
What is Henoch-Schoenlein Purpura?
Systemic IgA disease w/ Nephropathy and vasculiits
Skin Purpura
Abdominal Manifestations (Pain, vomiting, bleeding(
Arthralgias
What are the inherited glomerular diseases?
Alport Syndrome and Thin Membrane Disease (Benign Familial Hematuria)
What is Alport Syndrome? What happens? Histo? Clinical?
Nephritis, Nerve Deafness, Eye disorders, MEN!! (XL)
Defective GBM synthesis bc mutations of Alpha-5chains of Collagen type 4
Histology: Glomerular capillary BM are laminated - irregularly thickened or thinned w/ basket-weaving crisscorssing lines
Clinical: Hmeaturia, hearing, no col4a5 in skin
What is thin Membrane Disease? Benign Familial Hematuria?
Asymptomatic Hematuria w/ good prognosis and normal COL4A5
EM - see diffuse thinning of otherwise normal GBM
What is Membranoproliferative GN? What happens there? What are the 3 different pathogenesises?
- Glomerular syndrome w/ mixed pathology and can present as NS but w/ combined Nephritic features
- GBM Alterations (thickening) and Cell Proliferation - Mesangial increases in cells and Subendothelial depsosits
-TRAMTRACK
Pathogenesis:
1) Immune Complex Mediated - Hep B and Hep C, SLE, MGUS, MM, Lymphoma
2) Complement Mediated - Mutations or autoantibodies against complement regulating proteins
3) MPGN w/out immune complex or complement - Thrombotic microangiopathy, malignant HTN, etc
What is histology of Membranoproliferative GN?
Mesangial Hypercellularity, Endocapillary proliferation, Capillary wall remodeling and double contours - Lobular Accentuation of Glomerular Tufts
TRAM TRACK
Sub-endothelial immune deposits
See picture:
What systemic diseases can cause glomerular lesions?
SLE
Henoch-Schoenlein Purpura - IgA
Diabetic Glomerulosclerosis
Amyloidosis
What do yo usee in SLE nephritis?
Mesangial GN - mildest to Diffuse Proliferative GN - aggressive
“Full house” Immunofluorescence - all Ig, Complement components
