Nephrotic Syndrome I--Nichols/showkat

Front 1

What will you see in the clinical presentation of someone with NEPHROTIC syndrome?

Back 1

Lower extremity swelling
Pitting edema
Low albumin
4+ proteinuria
Spot urine protein creatinine ratio = 10.8

Front 2

What will you see in the clinical presentation of someone with NEPHRITIC syndrome?

Back 2

BP high
Blood urea nitrogen high
Creatinine high
Dysmorphic RBCs
Spot urine creatinine ratio = 1

Front 3

What are key differences between nephrotic and nephritic syndrome?

Back 3

Nephrotic = prominent edema, inactive urinary sediment, hypoalbuminemia, hyperlipidemia, non-inflammatory, normal BP, normal serum creatinine, key cell involved = visceral epithelial cell (podocyte) --> endothelial for nephritic

Front 4

What is indicated by the arrows?

Back 4

Urinary dipstick

Left = protein
Right = blood

Front 5

What is shown here?

Back 5

Normal appearing RBCs

Front 6

What is shown here?

Back 6

Dysmorphic RBCs

Front 7

What is this?

Back 7

Urinary sediment: hyaline cast

Front 8

What is this?

Back 8

Urinary sediment: white cell cast

Front 9

What is this?

Back 9

Urinary sediment: red cell cast

Front 10

What is this?

Back 10

Urinary sediment: granular cast

Front 11

What is the main target cell in nephrotic syndrome without glomerular inflammation?
Describe the injury types:

Back 11

Podocyte

Minimal change disease
Segmental glomerulosclerosis

Front 12

What happens in the case of immune complex formation and complement activation in the subepithelial space?

Back 12

Membranous nephropathy

Front 13

What are some glomerular capillary wall deposition diseases?

Back 13

Amyloidosis, light chain deposition disease, nephropathy

Front 14

What is the main target cell in nephritic syndrome with glomerular inflammation?

Back 14

Endothelium

Front 15

What are some causes of subendothelial space or mesangial immune complex formation and complement activation?

Back 15

Post-infectious glomerulonephritis
IgA nephropathy
Lupus nephritis

Front 16

What is the disease when antibodies are directed at the glomerular basement membrane?

Back 16

Anti-glomerular basement disease

Front 17

What is the disease that results in necrotizing injury and inflammation of the vascular and GCW?

Back 17

Antibodies against neutrophil cytoplasmic antigens (ANCA)-disease

Front 18

What is the clinical presentation of glomerular disease? ASYMPTOMPATIC

Back 18

Front 19

What is the presentation of glomerular disease? MACROSCOPIC HEMATURIA

Back 19

Front 20

What is the presentation of nephrotic syndrome?

Back 20

Front 21

What is the presentation of NEPHRITIC SYNDROME?

Back 21

Front 22

What is the presentation of rapidly progressive glomerulonephritis?

Back 22

Front 23

What is the presentation of chronic glomerulonephritis?

Back 23

Front 24

Properties that are necessary for glomerular filtration also predispose to what?

Back 24

Complex entrapment or formation

Front 25

What three things can cause immune complexes to be trapped in glomeruli?

Back 25

1. High plasma flow rate
2. High intraglomerular pressure
3. High glomerular hydraulic conductivity (permeability)

Front 26

What is the spectrum of immune complex disease dependent on?

Back 26

Nature of antigen involved and the site of immune complex deposition.

Front 27

Identify the labeled parts.

Back 27

Schematic Representation of three Glomerular Capillaries showing site of Immune Complex Formation:

1. Subepithelial Deposits: Post infectious GN and
2. Membranous Nephropathy.
3. Subendothelial and
4. Mesangial deposits: can be formed locally, but more commonly from passive entrapment of circulating ICs.
5. Anti-GBM Ab Disease: Abs bind in a linear fashion


EN= Endothelial Cell; EP = Epithelial Cell; MC= Mesangial Cell; MM= Mesangial Matrix

Front 28

What are three major causes of immune complex mediated glomerular disease? Think location and indicate nephrotic or nephritic

Back 28

1. Subepithelial deposits (nephrotic)
2. Subendothelial and mesangial deposits (nephritic)
3. Anti-glomerular basement membrane disease (usually nephritic with crescentic GN)

Front 29

What are two types of nephrotic subepithelial deposits?

Back 29

1. Membranous nephropathy
2. Post-infectious glomerulonephritis (seen later in course of disease)

Front 30

What are causes of membranous nephropathy (type of nephrotic subepithelial deposit)?

Back 30

1. Idiopathic
2. Systemic disorders: systemic lupus erythematosus, hepatitis B, drugs (gold, pencillamine)

Front 31

What are causes of sub endothelial and mesangial desposits (nephritic syndrome)?

Back 31

1. Focal of diffuse proliferative Lupus
2. Post-infectious glomerulonephritis- Early Phase
3. IgA nephropathy: With prominent IgA deposits in the mesangium

Front 32

What major signs do you see in nephrotic syndrome?

Back 32

1. Edema
2. Proteinuria
3. Hypoalbuminemia
4. Hypercholesterolemia/lipiduria

Front 33

If there is generalized edema, what should you evaluate for?

Back 33

Proteinuria

Front 34

What is shown in each image?

Back 34

Left = oval fat bodies
Right = maltese cross

Front 35

What is shown here?

Back 35

Xanthelasma in nephrotic syndrome

Front 36

Nephrotic vs. nephritic
Comment on the occurrence of each:
Hematuria
Proteinuria,
Edema
Hypertension

Back 36

All can occur in either

Front 37

What is the biggest difference between nephrotic syndrome and nephritic syndrome? I'm going to really burn up if I don't answer this correctly.

Back 37

Front 38

What are indications for biopsy?

Back 38

Guiding therapy or elucidating a failure to respond to therapy.

To determine diagnosis or prognosis.

Front 39

What are some contraindications for biopsy?

Back 39

Absolute: bleeding diathesis, uncontrolled hypertension

Relative: Single kidney, high pressure hydronephrosis, adult polycystic kidney disease

Front 40

What are the slide preparations for kidney biopsy?

Back 40

Light microscopy
Immunofluorescence
Electron microscopy

Front 41

Buzz words: Give association.

1. Foot process effacement
2. Spike and dome
3. Subepithelial humps

Back 41

1. Minimal change disease
2. Membranous nephropathy
3. Post-infectious glomerulonephritis

Front 42

4. Tram tracks
5. Basketweave
6. Wire loops
7. Onion-skin

Back 42

Front 43

The glomerular filtration barrier prevents the filtration of formed blood elements and proteins into the urinary space of Bowman’s capsule due to:

Back 43

1. Charge
2. Size
3. Shape

Front 44

Which are more easily filtered, small and cationic or small and anionic dextrans?

Back 44

Small or cationic

Front 45

What is the main site of size hinderance for larger molecules glomerular filtration? What is the estimated glomerular pore radius for spherical molecules?

Back 45

Lamina dense of GBM and slit diaphragm
42 angstroms

Front 46

What is the main side of hinderance of the anionic charge?

Back 46

Lamina rara interna and fenestrated capillary endothelium

Front 47

What prevents albuminuria?
What size uncharged molecules filter freely?
Which size are completely restricted?
Would albuminia occur if charge barrier did not exist?

Back 47

Size and charge barrier

Front 48

Some info about this during class?

Back 48

Maybe?

Front 49

Epithelial cells that line the proximal tubule take up protein by what mechanism?

What is considered a HMW protein?
What is intermediate?
What is LMW protein?

Back 49

Endocytosis
Endocytic vesicles --> fusion with lysosomes --> proteins hydrolyzed back into amino acids --> cross the basolateral membrane of the tubular epithelial cell and re-enter circulation

Front 50

Add notes from class.

Back 50

Add notes from class.

Front 51

Compare excretion of small molecular weight dextrans, clearance of large molecular weight dextrans, and excretion of IgG in nephrotic patients with normal subjects.

Back 51

Nephrotic patients:
1. Lower excretion of small MW dextrans (<48) secondary to loss of filtration surface area
2. Increased clearance of large MW dextrans with radius around 52 A (increase in large pores)
3. Increased excretion of IgG (neutral charge) due to loss of size barrier

Front 52

What are the three types of proteinuria?

Back 52

Glomerular
Tubular
Overflow

Front 53

What is glomerular proteinuria? What is dominant protein in urine?

Back 53

Front 54

What is tubular proteinuria? What is it secondary to?

Back 54

Front 55

What is overflow proteinuria? What is a condition where this occurs?

Back 55

Front 56

What protein does urine dipstick measure?

Back 56

Albumin!

Front 57

What is the typical range of protein excreted by healthy kidney? Upper range of normal? Healthy kidneys excrete about how much albumin per day? At what rate is Tamm-Horsfall mucoprotein excreted per day?

Back 57

40-80 mg/day
150 mg/day
30 mg/day
30-50mg/day

Front 58

When is the urine dipstick able to detect protein excretion?
What is the normal albumin/creatinine ratio?

Back 58

> 300-500 mg/day
Normal <30 mg/g

Front 59

What is defined as microalbuminuria?

Back 59

30-300 mg/day
Persistant

Front 60

What is normal for each?
Urine dipstick
24 hour collection
Spot urine protein creatinine ratio

Back 60

Urine dipstick = absent
24 hour collection = <150 mg
Spot urine protein creatinine ratio = <.15

Front 61

What is an abnormal urine dip stick?
What would the values be for the following in nephrotic range proteinuria?
24-hour urine collection:
spot urine protein creatinine ratio:

Back 61

1+, 2+. 3+

24 hour urine collection: >3.5 grams
Spot urine protein creatinine ratio: >3.5

Front 62

What is the goal of managing primary nephrotic syndrome?
What is the most important predictor?

Back 62

Goal: preserve kidney function
Most important predictor: proteinuria

Front 63

What are some supportive measures of proteinuria?

Back 63

Control hypertension (do this by having a low salt diet, angiotensin enzyme inhibitors, angiotensin receptor blocker).

Front 64

What are the two disease modifiers of proteinuria?
TREAT THE CAUSE

Back 64

1. Steroid
2. Immunosuppressive drugs (cyclophosphamide, cyclosporin, mycophenolate mofeitil, tacrolimus)

Front 65

Read summaries in lecture.

Back 65

Read summaries in lecture.

Front 66

Answer this!

Back 66

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Front 67

Answer this!

Back 67

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