Nephrotic & Nephritic Syndromes Flashcards
What are the clinical features of nephrotic syndrome?
- Hypoalbuminemia –> pitting edema
- Hypogammaglobulinemia –> increased risk of infection
- Loss of antithrombin III –> hypercoagulable state
- Hyperlipidemia & hypercholesterolemia –> fatty casts in urine
What is the most common cause of nephrotic syndrome in children?
Minimal change disease
What causes minimal change disease? What is it associated with?
Idiopathic; Hodgkin lymphoma
Minimal change disease results in which findings on
- H&E stain
- EM
- IF
- Normal glomeruli on H&E
- Effacement of foot processes on EM
- Negative IF
Why do patients with minimal change disease respond well to steroids?
Damage to foot processes mediated by cytokines from T cells
What demographic population is focal segmental glomerulosclerosis seen in?
Hispanics & African Americans; adults overall
What is focal segmental glomerulosclerosis usually associated with?
- HIV
- Heroin use
- Sickle cell disease
What is the most common cause of nephrotic syndrome in Caucasian adults?
Membranous nephropathy or membranous glomerulonephritis
What is membranous nephropathy associated with?
- Hep B or C
- Solid tumors
- SLE
- Drugs: NSAIDs and penicillamine
Where are immune complex deposits located in membranous nephropathy?
Subepithelial (beneath podocytes)
How does membranous nephropathy appear on EM?
Spike and dome appearance
Spikes = immune complexes; dome = additional BM laid down by podocytes
What is the pathogenesis of membrane thickening in membranous nephropathy?
Subepithelial immune deposits –> activate complement –> membrane thickening
Focal segmental glomerulosclerosis results in which findings on
- H&E stain
- EM
- IF
- Sclerosis focally and segmentally
- Effacement of foot processes
- Negative IF
Membranous nephropathy results in which findings on
- H&E stain
- EM
- IF
- Thickened glomerular BM
- Spike and dome appearance
- Granular IF
Membranoproliferative glomerulonephritis results in which findings on
- H&E stain
- EM
- IF
- Thick glomerular BM; increased number of cells/nuclei
- Immune complex deposits (subendothelial or intramembranous)
- Granular IF
What are some differences between Type I & II membranoproliferative glomerulonephritis?
Type I: subendothelial deposits; associated with HBV & HCV & more often tram track appearance
Type II = Dense Deposit Disease: intramembranous deposits; associated with C3 nephritic factor
How does hyaline arteriosclerosis occur in diabetes mellitus? Where in the glomerulus is it more likely to occur?
High serum glucose –> nonenzymatic glycosylation of vascular BM
*Efferent arteriole affected more –> higher glomerular filtration pressure –> microalbuminuria ———> nephrotic syndrome
Renal disease due to diabetes mellitus is characterized by what on H&E?
Sclerosis of mesangium + formation of Kimmelstiel-Wilson nodules
What medication can be administered to reduce the progression of hyperfiltration-induced damage in DM associated renal disease?
ACE inhibitors
Where in the kidney do amyloid deposits associated with systemic amyloidosis deposit?
Mesangium; also see nodules similar to DM
What is the main pathology in nephritic syndrome? What clinical symptoms does it lead to?
Inflammation and bleeding of glomerulus
- Limited proteinuria (< 3.5 g/day)
- Oliguria & azotemia
- Salt retention –> periorbital edema & HTN
- RBC casts & dysmorphic RBCs in urine
What does a kidney biopsy depict in a patient with nephritic syndrome?
Hypercellular, inflamed glomeruli
What are the main molecules mediating damage in nephritic syndrome?
Immune complex deposition –> complement activation –> C5a attracts neutrophils –> hypercellular, inflamed glomeruli
Where does immune complex deposition occur in post-streptococcal glomerulonephritis?
Subepithelial humps on EM
What is the clinical presentation of someone with poststreptococcal glomerulonephritis?
2-3 weeks after impetigo or pharyngitis –> hematuria, oliguria, periorbital edema, HTN
What comprises crescents seen in Rapidly Progressive Glomerulonephritis?
Fibrin and macrophages within Bowman’s capsule (outside glomerulus)
A linear IF pattern is indicative of what? What is the linear pattern due to?
Goodpasture syndrome; IgG antibodies against BM create a sharp line giving a linear pattern
A granular IF pattern is indicative of what? What is the granular pattern due to?
Immune complex deposition: PSGN, diffuse proliferative glomerulonephritis, membranous nephropathy, membranoproliferative glomerulonephritis; immune complexes are larger, have different solubilities and do not fit in glomerulus giving this granular pattern
What are the clinical signs of Goodpasture syndrome? Which population of individuals is it classically seen in?
Hemoptysis and hematuria; antibodies against glomerular & alveolar basement membrane commonly in young adult males
What is the most common type of renal disease in SLE?
Diffuse proliferative glomerulonephritis
Where does immune complex deposition occur in diffuse proliferative glomerulonephritis?
Usually subendothelial
Which rapidly progressive glomerulonephritis diseases does a negative IF suggest?
Wegener’s granulomatosis = granulomatosis with polyangitis, microscopic polyangitic, Churg-Strauss syndrome
What are clinical features of Wegener’s granulomatosis or granulomatosis with polyangitis?
- Glomerular nephritis
- Hemoptysis
- Nasal pharyngeal symptoms: sinusitis, rhinorrhea
- Myalgias
Positive c-ANCA is associated with which disease?
Wegener granulomatosis
Positive p-ANCA is associated with which disease?
Microscopic polyangiitis & Churg-Strauss syndrome
What are clinical features of Churg-Strauss Syndrome?
- Granulomatous inflammation
- Eosinophilia
- Asthma
* Distinguish Churg-Strauss from microscopic polyangiitis
Where in the kidney do IgA immune complexes associated with IgA nephropathy deposit?
Mesangium of glomeruli
What is the most common nephropathy worldwide?
IgA nephropathy = Berger disease
What is the clinical presentation for IgA nephropathy? When does it usually present?
Presents in childhood –> episodic gross or microscopic hematuria with RBC casts
*Episodic bc occur after mucosal infections (IgA elevated then)
What are the consequences of IgA nephropathy?
May slowly progress to chronic renal failure
What is the inheritance pattern for Alport Syndrome?
X-linked recessive
What is the defect in Alport syndrome? What effect does this have on the glomerulus?
Defect in type IV collagen; results in thinning & splitting of glomerular BM
What do people with Alport syndrome present with?
- Isolated hematuria
- Sensorineural hearing loss
- Ocular disturbances
- Family history of hematuria, dialysis/transplant
- Anterior lenticonus
