11 April wk6-A

Question 1

Why do patients with nephrotic syndrome have edema?

Answer 1

Nephrotic syndrome has greater than 3.5 g/day protein in urine. Primarily albumin. Loss of albumin in blood causes loss of oncotic pressure and fluid loss into the tissues.

Question 2

What are globulins?

Answer 2

Globulins are globular proteins that are a major component of the protein in blood.
Gamma globulins include antibodies
There are also Alpha-1,2 and Beta Globulins
All are higher molecular weight than albumin and have different solubility

Question 3

In nephrotic syndrome, lots of protein is lost in the urine. What effects does this have on the body, and the blood and its contents?

Answer 3

Hypoalbuminemia–edema
Hypogammaglobulinemia–increased infection
Hypercoagulable state–antithrombin III loss
Hyperlipidemia and Hypercholesterolemia–can cause fatty casts in urine

Question 4

What cells make up the filtration barrier in the kidney?

Answer 4

Endothelial cells from the capillaries
Basement membrane
Epithelial cells made up of the foot processes of podocytes

Question 5

When is immunofluorescence most helpful in assessing kidney disease?

Answer 5

It is only helpful when there are immune complex deposits, otherwise the test will be negative

Question 6

Patient is a child and has loss of albumin by the kidney but no loss of gamma globulins. Normal glomeruli on HandE, negative IF. What disease? Findings on EM? Cause? Treatment?

Answer 6

Dx: Minimal change disease (classic normal HandE stain)
EM: MCD has effacement of the foot processes of podocytes
Cause: excess production of cytokines–idiopathic or Hodgkin Lymphoma
Treatment: steroids to calm the immune response producing cytokines (only glomerular disease to respond to this treatment)
Negative IF because no immune complex deposition
Selective proteinuria = loss of albumin but not globulins

Question 7

What is the hallmark of minimal change disease?

Answer 7

Effacement of foot processes on EM
Normal glomerulus on HandE
Selective proteinuria
Response to steroids

Question 8

Patient known to have HIV and later develops nephrotic syndrome. What is the Dx?

Answer 8

Focal Segmental Glomerulosclerosis (FSGS)

Patients with HIV, using heroin, or with sickle cell disease tend to get this form of glomerular disease.

Question 9

What patient population tends to get FSGS?

focal segmental glomerulosclerosis

Answer 9

Hispanics and African Americans

Question 10

Patient has sickle cell disease and develops nephrotic syndrome. What Dx is most likely?

Answer 10

Focal Segmental Glomerulosclerosis (FSGS)

Question 11

Patient found to have effacement of the foot processes in the glomerulus. Prescribed a steroid and they do not improve. What disease was first considered and what is the actual condition that would progress to chronic renal failure?

Answer 11

Minimal change disease has effacement and does respond to steroids
FSGS also has effacement but does not respond. It is the progressed version of MCD.

Question 12

How are FSGS and MCD related and different?

Answer 12

Same: effacement of foot processes, no immune complex deposition
Different: response to steroids

Question 13

What is the most common cause of death in SLE patients and what forms of the disease do they get?

Answer 13

Most commonly die from kidney failure
Usually nephritic syndrome: Diffuse Proliferative Glomerulonephritis
If they get a nephrotic syndrome: membranous nephropathy

Question 14

Which nephrotic kidney disease is associated with Hep B C, solid tumors, SLE, or drugs?

Answer 14

Membranous nephropathy

Question 15

Patient with nephrotic syndrome found to have a thickening of the BM and a granular IF. What other classic feature seen on EM would identify this as membranous nephropathy?

Answer 15

Spike and dome appearance of the BM from immune complex deposition under the podocytes.

Question 16

Which nephrotic syndrome responds to steroids?

Answer 16

Minimal change disease only
The others do not:
FSGS, Membranous Nephropathy, Membranoproliferative

Question 17

What are the 6 causes of nephrotic syndrome and how should they be grouped?

Answer 17

Group them in 2’s
Minimal change and FSGS: both have effacement of the podocytes and no immune complexes

Membranous Nephropathy and Membranoproliferative: both have thickened membranes and immune complex deposition and granular IF

DM and Systemic amyloidosis: both systemic diseases

Question 18

Patient has nephrotic syndrome and thickened BM, granular IF, tram-track appearing EM. Dx? What are the types of this disease and their features?

Answer 18

Membranoproliferative Glomerulonephritis

Type I: subendothelial deposits associated with HBV and HCV

Type II: intramembranous deposits associated with C3 nephritic factor which stabilizes C3 convertase and overactivates complement causing inflammation and low levels of C3

Question 19

What are the classic findings for membranoproliferative glomerulonephritis?

Answer 19

Thick BM, granular IF, tram-track appearance on EM

Question 20

What are the diseases that deposit immune complexes in the glomerulus and where are the deposits?

Answer 20

Membranous nephropathy: subepithelial causing spike and dome appearance

Membranoproliferative: type I deposits subendothelial, type II deposits intramembranous

Question 21

Explain pathogenesis of diabetic nephropathy

Answer 21

High BG causes nonenzymatic glycosylation of the BM causes hyaline arteriolosclerosis. Also causes constriction of the efferent arteriole. Both cause hyperfiltration pressure leading to injury and microalbuminuria. Eventually progresses to nephrotic syndrome characterized by sclerosis of the mesangium with formation of Kimmelstiel-Wilson nodules that are pathognomonic for DM.
ACE inhibitors can slow progression by preventing ANG II constriction of efferent arterioles.

Question 22

What nephrotic syndrome causes apple-green birefringence under polarized light after staining with congo red?

Answer 22

Systemic amyloidosis
Kidney is most affected organ in this disease
Amyloid deposited in the mesangium leading to nephrotic syndrome

Question 23

What are the basic features of Nephritic syndrome?

Answer 23

Glomerular inflammation and bleeding
Limited proteinuria
Oliguria and Azotemia
Salt retention leading to fluid retention causing periorbital edema and HTN
RBC casts
Biopsy shows hypercellularity and inflamed glomeruli
Inflammation due to immune complex deposition activating complement including C5a which attracts neutrophils which cause the damage and hypercellularity

Question 24

Child presents with cola colored urine 2-3 weeks after having a skin infection with GABStrep (Impetigo)
What Sx might also be present? What is seen on HandE? EM? Treatment and outcomes for kids and adults?

Answer 24

Poststreptococcal Glomerulonephritis (PSGN)

Sx: Hematuria, oliguria, HTN, periorbital edema
HE: hypercellular, inflamed glomeruli
EM: subepithelial humps of immune complexes
Treatment: supportive
Outcome: kids 99% recover, adults 25% develop RPGN

Question 25

Patient has kidney biopsy that shows granular IF and subepithelial humps on EM. Dx?

Answer 25

PSGN (Post strep)

Question 26

Patient presents with Sx of nephritic syndrome and HE stain shows crescent formation. What is the general disease and what types are possible?

Answer 26

Crescents = rapidly progressive glomerulonephritis (crescents made of fibrin and macrophages)

Goodpasture syndrome
PSGN or Diffuse proliferative GN
Wegener granulomatosis or microscopic polyangiitis or Churg-Strauss syndrome

Question 27

Patient is young adult male presenting with hematuria and hemoptysis. Dx? Cause? Findings on HE, IF?

Answer 27

Goodpasture Syndrome (type of RPGN)
Cause: anti-basement membrane antibody attacks both the glomerulus and the alveoli
HE: crescent formation
IF: linear from anti-basement membrane antibody

Question 28

Patient found to have a rapidly progressing GN. IF shows a granular pattern and HE shows crescents. What is the Dx and some characteristics?

Answer 28

Dx: PSGN or Diffuse Proliferative GN
Cause: diffuse antibody-antigen complex deposition usually sub-endothelial
DPGN most common type of renal disease in SLE

Question 29

Patient has crescents on HE stain of glomeruli and has negative IF. Possible Dx?

Answer 29

Wegener Granulomatosis: c-ANCA
Microscopic Polyangiitis: p-ANCA
Churg-Strauss: p-ANCA, granulomatous inflammation, eosinophilia, asthma

Question 30

Patient has crescent glomeruli and linear IF findings. Dx?

Answer 30

Goodpasture Syndrome

Question 31

Patient has crescent glomeruli and granular IF and they have SLE. Dx? other possible Dx without SLE?

Answer 31

Diffuse Proliferative GN

PSGN

Question 32

Patient has crescent glomeruli and negative IF. Found to have c-ANCA. Dx? Sx?

Answer 32

Wegener Granulomatosis
Hematuria, Hemoptysis, Sinusitis
Careful in distinguishing this from goodpasture because of the hematuria and hemoptysis. c-ANCA, IF, and sinusitis make it different.

Question 33

Patient has crescent glomeruli and negative IF. Also have p-ANCA but no asthma or eosinophilia. Dx?

Answer 33

Microscopic Polyangiitis

Question 34

Patient has crescent glomeruli and negative IF. Also have p-ANCA, granulomatous inflammation, eosinophilia, and asthma. Dx?

Answer 34

Churg-Strauss

Question 35

Patient (usually child) found to have episodic hematuria with RBC casts following mucosal infections. Dx? Other findings?

Answer 35

IgA nephropathy (Berger Disease)
Most common nephropathy worldwide
IgA production to fight the mucosal infection deposits in the mesangium of the glomerulus
Seen as diffuse IgA on IF

Question 36

What are the hallmark findings in Alport Syndrome?

Answer 36

Familial hematuria–x-linked
Defect in type IV collagen causing thin BM
Isolated hematuria, sensory hearing loss, ocular disturbances