Nephrotic & Nephritic Syndromes

Question 1

What are the clinical features of nephrotic syndrome?

Answer 1

1. Hypoalbuminemia –> pitting edema
2. Hypogammaglobulinemia –> increased risk of infection
3. Loss of antithrombin III –> hypercoagulable state
4. Hyperlipidemia & hypercholesterolemia –> fatty casts in urine

Question 2

What is the most common cause of nephrotic syndrome in children?

Answer 2

Minimal change disease

Question 3

What causes minimal change disease? What is it associated with?

Answer 3

Idiopathic; Hodgkin lymphoma

Question 4

Minimal change disease results in which findings on

1. H&E stain
2. EM
3. IF

Answer 4

1. Normal glomeruli on H&E
2. Effacement of foot processes on EM
3. Negative IF

Question 5

Why do patients with minimal change disease respond well to steroids?

Answer 5

Damage to foot processes mediated by cytokines from T cells

Question 6

What demographic population is focal segmental glomerulosclerosis seen in?

Answer 6

Hispanics & African Americans; adults overall

Question 7

What is focal segmental glomerulosclerosis usually associated with?

Answer 7

1. HIV
2. Heroin use
3. Sickle cell disease

Question 8

What is the most common cause of nephrotic syndrome in Caucasian adults?

Answer 8

Membranous nephropathy or membranous glomerulonephritis

Question 9

What is membranous nephropathy associated with?

Answer 9

1. Hep B or C
2. Solid tumors
3. SLE
4. Drugs: NSAIDs and penicillamine

Question 10

Where are immune complex deposits located in membranous nephropathy?

Answer 10

Subepithelial (beneath podocytes)

Question 11

How does membranous nephropathy appear on EM?

Answer 11

Spike and dome appearance

Spikes = immune complexes; dome = additional BM laid down by podocytes

Question 12

What is the pathogenesis of membrane thickening in membranous nephropathy?

Answer 12

Subepithelial immune deposits –> activate complement –> membrane thickening

Question 13

Focal segmental glomerulosclerosis results in which findings on

1. H&E stain
2. EM
3. IF

Answer 13

1. Sclerosis focally and segmentally
2. Effacement of foot processes
3. Negative IF

Question 14

Membranous nephropathy results in which findings on

1. H&E stain
2. EM
3. IF

Answer 14

1. Thickened glomerular BM
2. Spike and dome appearance
3. Granular IF

Question 15

Membranoproliferative glomerulonephritis results in which findings on

1. H&E stain
2. EM
3. IF

Answer 15

1. Thick glomerular BM; increased number of cells/nuclei
2. Immune complex deposits (subendothelial or intramembranous)
3. Granular IF

Question 16

What are some differences between Type I & II membranoproliferative glomerulonephritis?

Answer 16

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

Question 17

How does hyaline arteriosclerosis occur in diabetes mellitus? Where in the glomerulus is it more likely to occur?

Answer 17

High serum glucose –> nonenzymatic glycosylation of vascular BM
*Efferent arteriole affected more –> higher glomerular filtration pressure –> microalbuminuria ———> nephrotic syndrome

Question 18

Renal disease due to diabetes mellitus is characterized by what on H&E?

Answer 18

Sclerosis of mesangium + formation of Kimmelstiel-Wilson nodules

Question 19

What medication can be administered to reduce the progression of hyperfiltration-induced damage in DM associated renal disease?

Answer 19

ACE inhibitors

Question 20

Where in the kidney do amyloid deposits associated with systemic amyloidosis deposit?

Answer 20

Mesangium; also see nodules similar to DM

Question 21

What is the main pathology in nephritic syndrome? What clinical symptoms does it lead to?

Answer 21

Inflammation and bleeding of glomerulus

1. Limited proteinuria (< 3.5 g/day)
2. Oliguria & azotemia
3. Salt retention –> periorbital edema & HTN
4. RBC casts & dysmorphic RBCs in urine

Question 22

What does a kidney biopsy depict in a patient with nephritic syndrome?

Answer 22

Hypercellular, inflamed glomeruli

Question 23

What are the main molecules mediating damage in nephritic syndrome?

Answer 23

Immune complex deposition –> complement activation –> C5a attracts neutrophils –> hypercellular, inflamed glomeruli

Question 24

Where does immune complex deposition occur in post-streptococcal glomerulonephritis?

Answer 24

Subepithelial humps on EM

Question 25

What is the clinical presentation of someone with poststreptococcal glomerulonephritis?

Answer 25

2-3 weeks after impetigo or pharyngitis --> hematuria, oliguria, periorbital edema, HTN

Question 26

What comprises crescents seen in Rapidly Progressive Glomerulonephritis?

Answer 26

Fibrin and macrophages within Bowman's capsule (outside glomerulus)

Question 27

A linear IF pattern is indicative of what? What is the linear pattern due to?

Answer 27

Goodpasture syndrome; IgG antibodies against BM create a sharp line giving a linear pattern

Question 28

A granular IF pattern is indicative of what? What is the granular pattern due to?

Answer 28

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

Question 29

What are the clinical signs of Goodpasture syndrome? Which population of individuals is it classically seen in?

Answer 29

Hemoptysis and hematuria; antibodies against glomerular & alveolar basement membrane commonly in young adult males

Question 30

What is the most common type of renal disease in SLE?

Answer 30

Diffuse proliferative glomerulonephritis

Question 31

Where does immune complex deposition occur in diffuse proliferative glomerulonephritis?

Answer 31

Usually subendothelial

Question 32

Which rapidly progressive glomerulonephritis diseases does a negative IF suggest?

Answer 32

Wegener's granulomatosis = granulomatosis with polyangitis, microscopic polyangitic, Churg-Strauss syndrome

Question 33

What are clinical features of Wegener's granulomatosis or granulomatosis with polyangitis?

Answer 33

1. Glomerular nephritis 2. Hemoptysis 3. Nasal pharyngeal symptoms: sinusitis, rhinorrhea 4. Myalgias

Question 34

Positive c-ANCA is associated with which disease?

Answer 34

Wegener granulomatosis

Question 35

Positive p-ANCA is associated with which disease?

Answer 35

Microscopic polyangiitis & Churg-Strauss syndrome

Question 36

What are clinical features of Churg-Strauss Syndrome?

Answer 36

1. Granulomatous inflammation 2. Eosinophilia 3. Asthma * Distinguish Churg-Strauss from microscopic polyangiitis

Question 37

Where in the kidney do IgA immune complexes associated with IgA nephropathy deposit?

Answer 37

Mesangium of glomeruli

Question 38

What is the most common nephropathy worldwide?

Answer 38

IgA nephropathy = Berger disease

Question 39

What is the clinical presentation for IgA nephropathy? When does it usually present?

Answer 39

Presents in childhood --> episodic gross or microscopic hematuria with RBC casts *Episodic bc occur after mucosal infections (IgA elevated then)

Question 40

What are the consequences of IgA nephropathy?

Answer 40

May slowly progress to chronic renal failure

Question 41

What is the inheritance pattern for Alport Syndrome?

Answer 41

X-linked recessive

Question 42

What is the defect in Alport syndrome? What effect does this have on the glomerulus?

Answer 42

Defect in type IV collagen; results in thinning & splitting of glomerular BM

Question 43

What do people with Alport syndrome present with?

Answer 43

1. Isolated hematuria 2. Sensorineural hearing loss 3. Ocular disturbances 4. Family history of hematuria, dialysis/transplant 5. Anterior lenticonus