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Renal Week 2 > Nephrotic Syndrome 1 > Flashcards

Nephrotic Syndrome 1 Flashcards

1
Q

What is a normal BUN?

A

10-20 mg/dl

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2
Q

What is a normal creatinine?

A

0.5-1.2 mg/dl

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3
Q

What is a normal albumin?

A

3.5-5 g/dl

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4
Q

Early markers of nephrotic syndrome over nephritic.

A
  • low albumin
  • lower extremity swelling/pitting prominent
  • normal BP
  • hypercholesterolemia/lipiduria
  • oval fat bodies, hyaline casts, rare RBCs
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5
Q

Early markers of nephritic syndrome over nephrotic.

A
  • elevated BUN and creatinine
  • normalish albumin
  • elevated BP (diastolic over 100)
  • abrupt onset, usually self-limiting
  • dysmorphic RBCs, heavy hematuria
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6
Q

What is the difference in spot urine protein creatinine ratio between nephrotic and nephritic syndrome?

A

nephrotic- 10+

nephritic- 1

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7
Q

Which syndrome has inflammation?

A

nephritic. Thus, urine will show active urinary sediment (proteinuria with cells and casts) in the form of dysmorphic RBCs and RBC casts in this only

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8
Q

What is the key cell involved in nephritic syndrome?

A

endotheial cell

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9
Q

What is the key cell involved in nephrotic syndrome?

A

visceral epithelial cell (podocyte)

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10
Q

Hyaline casts are usually fairly nonspecific, and usually seen in concentrated urine with any renal pathology, such as dehydration or use of diuretics. But it can also be associated different types of proteinuria. What types of casts are seen in nephritic syndrome?

A

White cell casts and RBC casts

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11
Q

When else can white cell casts be seen? RBCs?

A

UTI/pyelonephritis. BUT RBC casts is only found in glomerular disease.

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12
Q

When are granular casts seen?

A

When there is tubular damage from any cause such as acute tubular necrosis.

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13
Q

The mechanism of nephrotic syndrome can be divided in 3 groups based on the site of injury in the glomerular capillary membrane. What are the three sites?

A
  1. Injury can happen in podocytes
  2. Deposition of immune complexes in subepithelial space, under the podocytes
  3. Deposition in glomerular capillary wall
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14
Q

What diseases are injury of podocytes seen in?

A

Minimal change disease

Focal segmental glomerulosclerosis

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15
Q

What diseases is deposition of immune complexes in subepithelial space, under the podocytes seen in?

A

primary Membranous nephropathy

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16
Q

What diseases is deposition in glomerular capillary wall seen in?

A

Amyloidosis, LCD, DM nephropathy.

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17
Q

The mechanism of nephrItic syndrome can be divided in 3 groups, namely:

A
  1. Deposition of immune complexes in sub-endothelial space or mesangium
  2. Ab against the GBM
  3. Necrotizing injury and Inflammation of the vascular and glomerular capillary wall
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18
Q

What diseases is deposition of immune complexes in the SUB-ENDOTHELIAL space or mesangium seen in?

A

IgA nephropathy, PIGN, and Lupus nephritis

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19
Q

What diseases are Abs against the GBM seen in?

A

Anti-glomerular basement disease (Goodpasture’s).

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20
Q

What diseases is necrotizing injury and Inflammation of the vascular and glomerular capillary wall seen in?

A

ANCA vasculitis.

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21
Q

Why does necrotizing injury and Inflammation of the vascular and glomerular capillary wall occur in ANCA vasculitis?

A

which occur because of the Ab production against the neutrophil cytoplasmic Ag

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22
Q

T or F. Many properties of GFR predisposes immune complexes to be formed or trapped in the glomeruli

A

T.

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23
Q

What are some reasons that the glomeruli are susceptible to immune complex trapping?

A

High plasma flow: Large amount of blood passes through the kidney

There is high intraglomerular pressure

Increased permeability in the glomeruli.

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24
Q

The clinical presentation of glomerular disease is very diverse. What are some stages?

A
  • asymptomatic
  • macoscopic hematuria
  • nephrotic syndrome
  • nephritic syndrome
  • RPGN
  • chronic glomerulonephritis
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25
Q

What are some characteristics of asymptomatic glomerular disease?

A
  • proteinuria of 150-3000mg/day

- 2+ RBCS per HPF (usually dysmorphic)

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26
Q

What are some characteristics of macroscopic hematuria?

A
  • brown/red painless hematuria (no clots) that typically presents with concurrent infection
  • asymptomatic hematuria +- proteinuria between attacks
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27
Q

What is an example of macroscopic hematuria?

A

IgA nephropathy

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28
Q

Describe RPGN?

A

Similar to nephritic syndrome but its progression is rapid. Typical example would be ANCA associated vasculitis, lupus nephritis.

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29
Q

What are some examples of chronic glomerulonephritis?

A

slowly progressing renal dysfunction, along with proteinuria.

Typical examples are diabetic nephropathy and hypertensive nephropathy.

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30
Q

T or F. In some types of glomerular disease there are some times overlap between nephrotic and nephritis syndrome.

A

T. For example, common presentation of lupus nephritis is Nephritic syndrome or RPGN, however, it an also present as plain nephrotic syndrome just as macroscopic hematuria.

Similarly common clinical presentation of IgA nephropathy is macroscopic hematuria, however, it can also present as nephritis syndrome and RPGN

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31
Q

Why is hypercholesterolemia seen in nephrotic syndrome?

A

Hypoproteinemia stimulates protein synthesis in the liver, resulting in the overproduction of lipoproteins, as well as cholesterol and triglycerides

32
Q

Why do you see lipiduria in nephrotic syndrome?

A

lipoprotein lipase level decreases that leads to increased level of VLDL.

33
Q

If there is generalized edema, check for ____

A

proteinuria

34
Q

What is seen in the periorbital region in nephrotic syndrome?

A

Xanthelasma- Yellowish discoloration around the eye. Subcutaneous deposition of fat.

35
Q

What are some absolute contraindications to kidney biopsy?,

A

e.g. bleeding diathesis, uncontrolled hypertension

36
Q

What are some relative contraindications to kidney biopsy?

A

e.g. single kidney, high pressure hydronephrosis, adult PKD.

37
Q

What EM term is associated with minimal change disease?

A

foot process effacement

38
Q

What EM term is associated with Membranous Nephropathy?

A

Spike and Dome

39
Q

What EM term is associated with Post-infectious Glomerulonephritis?

A

Subepithelial humps

40
Q

What EM term is associated with Membranoproliferative Glomerulonephritis
?

A

Tram tracks

41
Q

What EM term is associated with Alports Syndrome

?

A

basket weave

42
Q

What EM term is associated with lupus nephritis?

A

wire loops

43
Q

What EM term is associated with hypertensive nephropathy or scherloderma?

A

onion-skin

44
Q

What are the surfaces of the podocytes and of the endothelium covered with?

A

A negatively charged glycocalix containing the sialoprotein podocalyxin (PC).

45
Q

What is the GBm composed of?

A

mainly of collagen IV (α3, α4 and α5), laminin 11 (α5, β2 and γ1 chains) and the heparan sulphate proteoglycan agrin.

46
Q

Podocytes are connect by slit membranes. What is the composition of slit membranes?

A
  • nephrin,

- Neph1, 2 and 3, -P-cadherin and -FAT1.

47
Q

What are β1α3 integrin dimers and what do they do?

A

Present in podocytes and specifically connect the TVP complex (talin, paxillin and vinculin) to laminin 11 in the BM

48
Q

What do a and B dystroglycans do?

A

connect utrophin in the podocytes to agrin in the BM

49
Q

How are slit membrane proteins joined to the cytoskeleton?

A

by various adaptor proteins, including catenins (Cat) connected to zonula occludes protein 1 in the podocyte and CD-2 associated protein (CD) connected to podocin in the BM

50
Q

What is TRPC6?

A

Molecule in podocytes that associates with podocin (and nephrin) near the slit membrane and allows Ca+ influx into podocytes

51
Q

Prevention of filtration of formed blood elements and proteins into the urinary space of Bowman’s capsule is regulated by:

A
  • Charge
  • Size
  • Shape
52
Q

Uncharged macromolecules less than ____ filter freely.

A

1.8 nm. While, Molecules > 4 nm completely restricted

53
Q

Albumin has an effective radius of 3.6nm. What keeps it out of the urine normally (not size)?

A

the negativity of the BM (sialoprotein podocalyxin (PC).)

54
Q

Assuming similar size, what is the order of filtration clearance of cationic, neutral, and anionic molecules?

A

cationic more than neutral more than anionic due to BM negativity

55
Q

What is the main site of hindrance for larger molecules?

A

The Lamina Densa of the GBM and the Slit Diaphragm

56
Q

What is the main site of hindrance for charge?

A

The anionic charge on the Lamina rara interna, and on the fenestrated capillary endothelium.

57
Q

What is a LMW molecule that is free filtered?

A

B2 microglobulin

58
Q

Is any albumin (intermediate radius 3.6nm) filtered into the glomerulus?

A

yes, about 1mg/dl (almost all should be reabsorbed quickly in the PT so hardly any in urine)

59
Q

How are proteins taken up into the PT?

A

Recent evidence that protein is absorbed by receptor-mediated endocytosis [megalin & cubulin] which are multiligand receptors.

60
Q

What happens to reabsorbed proteins?

A

The endocytic vesicles eventually fuse with lysosomes where the proteins are hydrolyzed into amino acids, which cross the basolateral membrane of the tubular epithelial cell and re-enter the circulation.

61
Q

What happens to the podocytes in proteinuria?

A

fusion of the visceral epithelium

62
Q

How can proteinuria be managed even given damage to the epithelium?

A

Filtration of substance such as albumin is affected by intraglomerular pressure. So, if we decreased the IG pressure that will help to lower albumin loss, inspite of the podocyte injury.

63
Q

T or F. Nephrotic patients have lower excretion of small molecular weight dextrans (

A

T., and Increased clearance of large molecular weight dextrans (>52), compared with normal subjects because of increase in large pores.

Also increased excretion of IgG (neutral charge) due to loss of size barrier

64
Q

What protein does urine dipstick measure?

A

albumin

65
Q

What are the types of proteinuria?

A
  • glomerular
  • tubular
  • overflow
66
Q

What condition is associated with overflow proteinuria?

A

multiple myeloma

67
Q

What is normal urine protein?

A

40-80 mg/day of protein may be excreted by healthy kidney. (150 mg/day is the upper range of normal)

Tamm-Horsfall protein which is derived from tubule excreted at 30-50 mg/day.

68
Q

Urine dipstick only turns +ve when?

A

the protein is albumin, and the amount is 300-500 mg/day.

69
Q

So how we do detect proteinuria less than 300 mg?

A

Use ratio of albumin to Cr in urine

Urine albumin and Cr ratio corresponds fairly accurately with proteins in 24 hour urine collection.

or use microalbuminuria

70
Q

What is a normal urine albumin/ creatinie ratio?

A

less than 30mg/g

71
Q

Microalbuminuria normally detects protein __ to ___ mg/day.

A

30 to 300

72
Q

Ways to measure proteinuria

A

Urine dipstick indicate proteinuria in the form of 1+, 2+, 3+

Can collect urine for 24 hr and measure the protein. Normal is

73
Q

T or F. We consider nephrotic syndrome when 24 hr urine showed >3.5 gm proteinuria or spot protein CR ratio >3.5

A

T.

74
Q

What is the goal of treatment of nephrotic syndrome?

A

preserve renal function

75
Q

The most important indicator of progression of nephrotic syndrome is what?

A

proteinuria

76
Q

What are some supportive measures for managing primary NS?

A

Control HTN

 - low salt diet
 - ACEIs
 - ARBs
77
Q

What are some disease modifiers for NS?

A
  • steroids

- Immunosuppressive drugs (Cyclophosphamide, cyclosporin, tacrolimus, mycophenolate mofetitil

Renal Week 2 (13 decks)

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