Seventeen Flashcards
(50 cards)
What are the 4 components of the glomerus with subcomponents?
• Epithelial cells
– Visceral
– Parietal
- B tM b asement Membrane
- Endothelial cells
- Mesangium
– Cells
– M ti a r x
Describe visceral epithelial cells and their function.
- Podocyte
- F too processes
- Attach to BM via adhesion proteins (integrins)
- Produce, maintain GBM
- Filtration slits extend between foot processes
• Slits are major barrier to passage of plasma
proteins
Describe the filtration slit diaphragm including the proteins involved and the function.
- Modified adherens junction
- Critical role in glomerular filtration barrier
- SD proteins control glomerular permeability
• Podocin, nephrin, CD2AP interact with membrane
proteins actin cytoskeleton proteins, actin cytoskeleton
Describe the GBM
- Made by VEC
- 300 nm thick
- 3 layers
- Type IV collagen, laminin,
fibronectin, proteoglycans,
glycoproteins
• Anionic
What are the functions of the mesangium?
- Contract
- Phagocytosis
- Synthesize matrix,
cy g tokines, growth factors
• Can proliferate and lay down
new matrix
• Continuous with
extraglomerular cells of JGA
What are 4 possible etiologies of glomerular injury?
• Glomerulus – Immune-mediated – Hemodynamic – GBM abnormality – Podocyte abnormality
What are 3 possible visceral epithelial cell pathologies? What can happen with parietal epithelial cells?
• Visceral
– Foot process effacement (fusion)
– Detach from GBM
– Subepithelial (epimembranous) immune deposits
• Parietal
– Proliferate (crescent)
What are 6 GBM pathologies?
- Too thick
- Too thin
- Too permeable
- Infiltrated
- Anti-GBM
- Intramembranous immune deposits
Name 2 endothelial cell pathologies.
- Proliferate
- Subendothelial immune
deposits
Name 4 mesangial pathologies.
• Cells/matrix increase – Expand mesangial area – Interpose between endothelium and GBM endothelium and GBM“interposition” • Inflamed • Intramesangial immune deposits
What do focal, diffuse, segmental, and global mean? What do endocapillary and extracapillary refer to?
Focal-some glomeruli in the kidney
Diffuse-all glomeruli
Segmental-only some parts of the glomerulus
Global-The whole glomerulus
• Increased cells
– Endocapillary
– Extracap y( ) illary (crescent)
What are immune deposits? What do they do? What are 4 ways in which they get to the glomerulus? Where in the glomerulus do the immune complexes deposit?
- Deposit = Immune complex
- A ti n gen-A tib d Antibody
complexes
• Complement activation and Complement activation and
induction of cytotoxic or p y roinflammatory complement components
• Activate macrophages, mesangial cells
• Circulating Ag-Ab compl t di ex trapped in
glomerulus
– Exogenous Antigen Exogenous Antigen
– Endogenous Antigen
• Ab reacts Ab reacts in-situ
– Fixed intrinsic Antigen
–“Planted” Antigen
- Subepithelial (epimembranous)
- Subendothelial
- Intramembrano s Intramembranous
- Mesangial
Describe the two clinical presentations of glomerular disease. What is pathognomonic for glomerular disease? Which test is necessary?
Nephrotic Syndrome
• Proteinuria (PU) – 3-3.5 g/24h • Hypoalbuminemia • Edema • Hyperlipidemia
Nephritic Syndrome • Hematuria – RBC casts • Oliguria, azotemia (BUN) • Hypertension • Proteinuria
Marked proteinuria or hematuria with RBC cast th i f ts pathognomonic glomerular disease.
Urinalysis
What are the causes of hypoalbuminemia in nephrotic syndrome? What is the cause of hyperlipidemia? Describe the pathophysiology of nephrotic syndrome. Describe the
• Hypoalbuminemia
– Urine loss
– ? Hepatic synthesis ↓, renal degradation ↑, extra renal
disposition change.
• H li id i Hyperlipidemia
– ↑ VLDL synthesis
Increased permeability to plasma proteins
• Lose size, charge selective protein barrier
• Structural, physicochemical change
– GBM proteoglycans
– Endothelium/epithelium sialoglycoprotein coat
– Slit diap g hra m
What are 6 causes of nephrotic syndrome? How does the likelihood of the causes differ between adults and children?
• Diagnosis varies with age
• Children: Primary renal disease, minimal change
disease FSGS
• Adults: Primary or syst i em c disease, membranous
glomerulopathy
- Minimal Change Disease
- Focal Segmental Glomerulosclerosis (FSGS)
- Membranous
- MPGN
- Diabetes
- Amyloidosis
What are some other names for minimal change disease? What are some its clinical characteristics? What does MCD look like with LM/EM?
- Lipoid nephrosis
- Nil disease
- MCD
- Nephrotic syndrome
- Children»Adults
- Selective proteinuria
- Normal renal function
- Steroid responsive
- Not immune complex- mediated
- T-cell mediated VEC damage with cytokine release, GBM or slit diaphragm damage
- Loss of glomerular polyanion
- Mutation in nephrin
Light microscopy
Normal glomeruli
Lipoid Nephrosis (sloughing off of the epithelium (which contains lipid) into the PT lumen, which results in oval fat bodies in urine)
EM
Complete foot process effacement
What is FSGS? What are some of its clinical characteristics?
What are some of its epidemiological characteristics? What is the most common cause of FSGS? What are some other causes?
Focal segmental glomerulosclerosis
• Nephrotic syndrome • Nonselective proteinuria • Less steroid responsive than MCD, >50% ESRD in 5 yrs. • Adults - 35% of NS, Children 10% of NS • More prevalent in African- American, Hispanic
- Primary (idiopathic) most common
- Renal ablation nephropathy, obesity
- “Healed” glomerulonephritis
- HIV, heroin, SS disease
- Mutations in slit diaphragm proteins
What causes primary FSGS? What causes secondary FSGS?
Primary
• VEC injury
• Circulating factor,
cytokine?
Secondary
• Hemodynamic injury-Reduced nephron number relative to body mass (unilateral agenesis, advanced renal disease, obesity)
• Mutation in gene for slit diaphragm protein
– Nephrin, podocin, alpha-actinin-4 TRPC6 4, TRPC6
What does FSGS look like histologically? In LM? EM?
LM
• Sclerosis of some, but not all glomeruli (FOCAL
• Sclerosis affects a segment but not all of a glomerulus
(SEGMENTAL)
EM
– Fusion of foot processes (effacement)
– Epithelial detachment
What are some synonyms for membranous nephropathy? What are some clinical characteristics of membranous nephropathy? What is the most common cause? What are some other causes? What are some other association?
Epimembranous glomerulonephritis Membranous glomerulonephritis Membranous glomerulopathy MGN MN
PU or Nephrotic Syndrome
Adults>Children
25% progress to failure
Usually primary
• Autoimmune disease • Carcinoma – Lung, colon, melanoma • Drugs – Gold, penicillamine, NSAIDs • Infections – Hep B, C, syphilis, malaria • Other associations – DM, Renal vein thrombosis • ATIII, Protein C and S lost in urine
Describe the pathogenesis of membranous nephropathy.
Chronic immune complex deposition
• In-situ formation: antibody to endogenous VEC autoantigen (autoimmune disease) or planted ag
• Circulating immune complexes:
Endogenous or exogenous ag
What is the most common antigen responsible in membranous nephropathy? In which type is it most common? What other antigens can be responsible?
• Endogenous in VEC
– In 70% of adults VEC phospholipase A (PLA2R) 2 receptor
– Neutral endopeptidase (NEP)
• Planted antigen Planted antigen
– Hep B, C proteins
– dsDNA histone RNA
Describe the LM pathology in membranous nephropathy. EM pathology? Immunoflourescence?
LM
No glomerular inflammation, no intracapillary proliferation
• Spikes on subepithelial GBM
EM
• Subepithelial (epimembranous) immune deposits
• Spikes are projections of lamina densa around deposits
Immunoflourescence
• Diffuse granular immune deposits along GBM
(antibody + complement)
What are some synonyms for membranoproliferative glomerulonephritis? What are some clinical characteristics? What are the types?
MPGN
Mesangiocapillary GN
Hypocomplementemic GN
Lobular GN
• Children, young adults
Nephritic OR nephrotic
- Hypocomplementemic
- Can progress to ESRD
Two types Type I Type II (Dense Deposit Disease)