Flashcards in L76- Kidney diseases I Deck (93):
Location of kidneys?
Locate in retroperitoneum
Vertebra: T12 - L3
Functions of Mesangium?
-Structural - hold capillary loops together
-analyze urine in distal
-contract to reduce
What is primary renal diseases?
kidney is the only/ predominant organ involved (no systemic manifestation)
What is secondary renal diseases?
kidney is injured in the
course of systemic diseases or infections
What is clinical-pathological diagnosis?
clinical hisotry and manifestations
Renal biopsy pathological diagnosis
3 methods to examine renal biopsy?
-Direct immunofluorescnce study
Explain how nephrotic syndrome can lead to hyperlipidemia?
Kidney glomeruli leak albumin:
> heavy proteinuria , hypoalbuminemia = reduced oncotic pressure
> Generalized edema
> Liver synthesizes proteins (e.g. lipoproteins) to compensate oncotic pressure
How does nephrotic syndrome affect drug levels?
Decrease in serum-binding protein > some drugs less able to be transported
How does nephrotic syndrome affect clotting and cause Deep vein thrombosis?
>> enhanced venous / arterial thromboembolism
How does nephrotic syndrome affect immunity?
Loss of Ig, complements, impaired neutrophil phagocytic function >> increase risk of infection
How does the kidney fail in nephrotic syndrome?
Summarize all the complications of nephrotic syndrome?
Progressive renal failure
Increase risk of infection
Decrease in serum-binding protein
Hyperlipidemia and lipiduria
Presentation of nephritic syndrome in urine?
1) Mild to moderate proteinuria
2) Acute onset, gross visible hematuria or;
3) Microscopic hematuria with red cell casts
Presentation of nephritic syndrome in GFR and BP?
Which glomerular diseases are related to nephritic syndrome?
1) Acute poststreptococcal glomerulonephritis
2) Rapidly progressive glomerulonephritis
What is the presentation of acute kidney injury?
- rapidly decline in GFR in hours/ days
- Severe form: oliguria (reduced urine) or anuria (no urine)
What is the definition of chronic kidney disease?
presence of kidney structural / functional abnormalities for
at least 3 months
Persistent declined GFR (< 60mL/min/1.73m^2) for at least 3 months
What type of disease is acute kidney injury associated with?
Glomerular, interstitium, tububles, blood vessel diseases
GFR in end stage renal disease?
GFR < 5% of normal
Final and irreversible
Treatment for end stage renal disease?
Renal replacement therapy:
2) Peritoneal dialysis
3) Kidney transplant
Biochemical abnormality referring to elevation of blood urea, nitrogen and creatinine levels
Decrease in GFR
Toxic condition resulting from kidney disease
Retention of waste products (normally excreted) in bloodstream
What are the 3 categories of glomerular diseases? *
Systemic disease with glomerular involvement
Which glomerular diseases are related to nephrotic syndrome?
Just rmb the top 4
1) Focal segmental glomerulonephritis
2) Membranoproliferative glomerulonephritis
3) Membranous neuropathy
4) Minimal change disease
(Amyloidosis, Diabetes mellitus, SLE)
What are the primary glomerulonephritis/ glomerulopathy diseases?
Focal segmental glomerulonephritis
Rapidly progressive (crescentic) Glomerulonephritis
Acute post-infectious glomerulonephritis
What are the systemic diseases with glomerular involvement?
(Microscopic polyangiitis, Wengener granulomatosis, Henoh- Scholein purpura)
Name 3 hereditary syndromes that causes kidney damage? *
Thin basement membrane disease
What is the most common mechanism of glomerular injury pathogenesis?
Immune, Ag-Ab reactions
3 ways that immune mechanism causes glomerular injury? *
1) Ab react in-situ within glomerulus
2) Deposition of circulating Ag-Ab complexes in glomeruli
3) Ab directed against normal components of GBM
4) Cell-mediated or alternative complement immune injury
Apart from immune damage, what are the 2 other ways glomerular injury occurs?
Metabolic alterations of GBM
Genetic defect of GBM synthesis and cellular protein
3 locations for Ag-Ab complexes to deposit to cause glomerular injury?
1) Subendothelial deposit
1) Within GBM
2) SubEPITHELIAL deposit (outside capillary)
2 things that lead to uremia?
Decrease glomerular blood flow
What causes primary membranous nephropathy? *
binding of autoantibodies
to M-type phospholipase A2 receptor (PLA2R) expressed on podocytes
What causes secondary membranous nephropathy?
-Infection (Hepatitic B or C)
-Autoimmune disease (SLE, Rhuematoid arthritis)
Pathogenesis of membranous nephropathy?
Chronic in situ deposit of Ig containing immune complex in subepithelial space along GBM
light microscopy appearance of membranous nephropathy? Give stains
• Holey, frothy, bubble, spiked appearance on GBM in Silver stain
• Diffuse thickening of capillary wall in H&E stain
Immunofluorescence appearance of membranous nephropathy?
Granular deposition in Subepithelial space
(in-situ deposition, not circulation)
Electron microscopy appearance of membranous nephropathy?
In subepithelial space
Main clinical manifestations of nephrotic syndrome?
Proteinuria (3.5 g or more in adults/day)
Hyperlipidaemia and lipiduria
What is the marker for Primary membranous nephropathy?
What is the treatment of primary and secondary membranous nephropathy?
Primary = steroids
Secondary = Treat underlying cause
What are the outcomes of membranous nephropathy?
60% pateints have persistent proteinuria
10% progress to renal failure in 10 years
Age group affected by membranoproliferative glomerulonephritis ?
Children and young adults
Presentation of membranoproliferative glomerulonephritis?
Nephrotic syndromes (e.g. generalized edema, hyperlipiduria...etc)
What are the 4 types of membranoproliferative glomerulonephritis?
Dense Deposit disease
Light microscopy of membranoproliferative glomerulonephritis?
Hypercellularity: Cellular proliferation of mesangial cells + Leukocyte infiltration
Capillary wall thickening
Basement membrane splitting
Immunofluorescence appearance of membranoproliferative glomerulonephritis?
dense deposits at capillary walls subendothelium
Explain electron microscopy of membranoproliferative glomerulonephritis
Splitting of glomerular basement membrane
immune deposition at subendothelium causes formation of new GBM under original GBM
Treatment of membranoproliferative glomerulonephritis?
Treat underlying cause
Drugs targeting C3 glomerulonephritis
Outcome of membranoproliferative glomerulonephritis?
50% develop chronic renal failure within 10 years
Pathology of Minimal change disease?
injure podocytes and cause proteinuria with effacement of foot processes
Exact cause unknown
Age groups affected by minimal change disease?
Most common (90%) nephrotic syndrome in children
Peak incidence at 2-6 years old
Associated factors that can lead to minimal change disease?
Drugs (e.g. NSAID and Interferons)
Infection and recent vaccination
Light microscopy of minimal change disease?
glomeruli that have a normal appearance
Immunofluorescence of minimal change disease?
Electron microscopy of minimal change disease?
Diffuse (more than 50%) effacement of foot processes of podocytes
>> loss of filtration slit
Treatment of minimal change disease>?
(little steroid-dependence or resistance)
Outcome of minimal change disease?
Prognosis is excellent
Given the exact cause of minimal change is unknown, what are some possible etiologies?
Abnormality in cell-mediated immunity
Complication of minimal change disease? Explain
GBM lose protein filter function
Lose albumin > blood oncotic pressure decrease
> increase filtration into tissue and hypovolemic shock
> Pre-renal damage and acute tubular necrosis
> Acute renal failure
Pathology of Focal segmental glomerulosclerosis (FSGS)?
<50%, partial glomerulosclerosis:
Replacement of capillary loops of glomerulus by ACELLULAR, AMORPHOUS material*
*derived from plasma protein, collagen, basement membrane materials
Primary FSGS presentation and features are similar to which nephrotic disease?
Differential diagnosis between minimal change and FSGS?
FSGS has no response to steroids (but minimal change has excellent response)
FSGS = more likely to progress to chronic renal failure and recurrence after transplant
Is Acute proliferative / post-infectious glomerulonephritis nephrotic or nephritic?
Pathology of Acute proliferative / post-infectious glomerulonephritis?
Immune complex glomerulonephritis
usually preceded by Group A, B-haemolytic streptococci infection of pharynx (1-4 weeks before)
Age group most affected by Acute proliferative / post-infectious glomerulonephritis?
What other infections can precede Acute proliferative / post-infectious glomerulonephritis?
Virus (HBV/ HIV/ HCV)
Parasites (malaria/ toxoplasmosis)
Light microscopy of Acute proliferative / post-infectious glomerulonephritis?
Hypercellular glomeruli with neutrophils
Explain where the immune complex deposition occurs in Acute proliferative / post-infectious glomerulonephritis?
Immune-complexes formed by antibodies and circulating or planted antigens
>> depositing in the subepithelial space, forming lumps
Immunofluorescence appearance of Acute proliferative / post-infectious glomerulonephritis?
Spotty immune deposits
"Starry sky" appearance due to deposits of IgG (and complement 3)
Electron microscopy appearance of Acute proliferative / post-infectious glomerulonephritis?
Electron dense deposits forming subepithelial humps at GBM
Outcome of appearance of Acute proliferative / post-infectious glomerulonephritis?
95% recover with conservative therapy
Explain Hypercellular glomeruli
in Acute proliferative / post-infectious glomerulonephritis?
Injury to glomerular tufts > leakage of plasma protein
stimulates Bowman’s capsule
>> parietal epithelium proliferates
>> enlarged, hypercellular glomeruli
What is rapidly progressive (crescentic) glomerulonephritis associated with?
Severe glomerular injury with multiple possible causes:
Type I,II, III
Name a type I rapidly progressive (crescentic) glomerulonephritis?
= Anti-GBM antibody mediated glomeruplonephritis
Name 4 type II rapidly progressive (crescentic) glomerulonephritis?
Immune complex mediated:
Acute poststreptococcal glomerulonephritis
(Henoch- Schonlein purpura)
Name a type III rapidly progressive (crescentic) glomerulonephritis?
Pauci- immune mediated:
ANCA-associated (Wegener granulomatosis, microscopic polyangiitis)
Goodpasture syndrome pathology in kidney?
Autoantibody attack noncollagenous C terminal (NC1) domain of alpha 3 chain of collagen type IV at GBM
Goodpasture syndrome pathology in lungs?
Autoantibodies cross-react with pulmonary alveolar basement membranes>> cause pulmonary haemorrhage and death
What precedes goodpasture syndrome?
Hydrocarbon or solvent exposure
Light microscopy appearance of Goodpasture? *
Focal necrotizing lesions
Cellular crescent at Bowman's capsule
Diffuse parietal epithelium proliferation
immunofluorescence appearance of Goodpasture?
" Linear ribbon deposition" of IgG along GBM
Electron microscopy appearance of Goodpasture?
No deposit by usual electron microscopy
>> antibodies too small to be detected
Treatment of goodpasture syndrome?
Plasmapheresis/ plasma exchange
High dose steroid and Cyclophosphamide
Outcome of good pastures syndrome?
Chronic renal replacement therapy or kidney transplant
What type of disease in IgA nephropathy?
Immune complex glomerulonephritis
What is the most common cause of Glomerulonephritis worldwide?
What are the presentations of IgA nephropathy?
Microscopic/ macroscopic haematuria
Proteinuria (10% nephrotic range)
Chronic or acute kidney failure
Light microscopy appearance of IgA nephropthy? *PAS stain*
Mesangial hypercellularity with increased matrix
Capillary loop not much affected
immunofluorescence appearance of IgA nephropthy?
Dominant or co-dominant deposits of IgA at mesangial cells
Electron microscopy appearance of IgA nephropthy?
Mesangial electron dense deposits (immune complexes)
Treatment of IgA nephropathy?
Depends on clinical setting
Corticosteroid if significant proteinuria or rapidly progressive kidney injury