SM 205a/208a/209a/212a - Renal Syndromes, Nephrosis, Nephritis Flashcards Preview

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Flashcards in SM 205a/208a/209a/212a - Renal Syndromes, Nephrosis, Nephritis Deck (80)
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1
Q

Characteristic of nephritic or nephrotic syndrome?

WBC casts

A

Neither

Interstitial cause likely

2
Q

Kimmelsteiel-Wilson nodules are pathopneumonic for which renal syndrome?

A

Diabetic nephropathy

3
Q

What conditions might FSGS be secondary to?

A

HIV + Heroine use

Reduced renal mass

Hyperfiltration injury

Obesity

4
Q

What pathologic findings are present?

A

Focal segmental glomerulosclerosis

Not all glomeruli show sclerosis (focal)

Only parts of the affected glomeruli are affected (segmental)

5
Q

How does sepsis affect glomerular macromolecule handling?

A

Sepsis -> Podocyte dysfunction

  • Alters slit diaphragm structure and function
  • More proteinuria
6
Q

What is the treatment for minimal change disease?

What should you consider if there is no response?

A

Steroids

If no response, consider FSGS

If initial response but frequent relapse, try steroid-sparing immunosuppressive agents

7
Q

Characteristic of nephritis or nephrosis?

Low serium albumin

A

Nephrosis

8
Q

What are the differences in the presentation of IgA nephropathy and PIGN?

A
  • Timing
    • IgA nephropathy is synpharyngitic and recurrent
      • Occurs at the same time or soon after URI or sore throat
      • Patient may report that they have had other episodes of hematuria throughout their lives
    • PIGN occurs after infection (7-14 days), and is not recurrent
  • Biopsy
    • IgA nephropathy shows mesangial deposits
      • LM: Mesangial proliferation
      • FM: Granular mesangial deposits
      • EM: Mesangial deposits
    • PIGN shows granular deposits
      • LM: Hypercellularity
      • FM: Starry sky
      • EM: Sub-epithelial humps
9
Q

What levels of proteinuria qualify as “nephrotic range?”

A
  • Adults: 3 gm/day
  • Children: 50 mg/kg/day
  • Urine Prot: Urine Creatinine > 2
10
Q

What is “nephrotic-range proteinuria?”

A

Proteinuria >2.5 - 3 grams/day

Can use (urine protein / urine creatinine) = grams of protein/day
as a proxy for 24h urine collection

11
Q

Which patients with suspected nephrotic syndrome are not routinely biopsied?

A

Children

If suspicion is high for minimal change disease, treat empirically with corticosteroids

If the patient recovers, it was likely MCD and you avoided doing an invasive procedure :)

12
Q

Which renal syndromes result from primary glomerular disease?

A

Membranous nephropathy (nephrotic)

Membranoproliferative glomerulonephritis (nephritic)

13
Q

What is the classic finding for Pauci-Immune Glomerulonephritis?

A

ANCA

Pauci-Immune = microscopic polyangiitis (p-ANCA) or
granulomatosis with polyangiitis (c-ANCA)

14
Q

Glomerular handling of macromolecule is dependent on…

A

Size and charge

15
Q

Which renal syndrome will show linear IgG deposits on FM?

A

Anti-GBM disease

(aka RPGN Type I)

A nephritic syndrome

16
Q

Why is important to identify and treat membranous nephropathy quickly?

A

To avoid potential complications

  • Renal vein thrombosis
  • Pulmonary embolism due to hypercoagulability
17
Q

What renal syndrome shows this pattern on immunofluorescence?

What would you expect from the patient’s history?

A
  • IgA Neprhopathy (nephritic)
    • Deposits in the mesangium instead of the basement membane
    • We would expect them to be IgA
  • History
    • Recurrent hematuria (tea/cola colored urine) associated with URI or pharyngitis
    • Synpharyngitic - occurs during or very soon after infection
18
Q

What is the mechanism of hyperlipidemia in nephrotic syndrome?

A

Multiple potential causes

  • Increased hepatic lipoprotein synthesis
    • Oncotic/viscosity signal
    • May be overlap with albumin synthesis pathway and lipid synthesis pathway
  • Defective lipid transport
    • HDL lost in urine
  • Decreased LPL and LCAT activity
    • Albumin binds to the products of cholesterol breakdown
    • Loss of albumin = cannot bind to products = le chaltlier towards the reactants
      • Decreaed cholesterol breakdown
19
Q

What is the treatment for lupus nephritis?

A

Depends on the level of inflammation

  • Minimal inflammation
    • Focus on treatment of lupus
  • Active inflammation
    • High-dose steroids + immune-modulating drugs
      (important to control inflammation to protect the kidney)
20
Q

Which renal syndromes are associated with a history of Hep B and Hep C?

A
  • Nephrotic
    • Membranous nephropathy
  • Nephriti
    • MPGN
21
Q

Apple-green birefringensce in polarized light on a congo-red stain is characteristic of what pathologic finding?

A

Amyloidosis

22
Q

The most critical determinant of whether or not a molecule of effective Stokes radius = 40 Å is filtered by the glomerulus is:

a. Blood pressure
b. Hydration status
c. The endothelial glycocalyx
d. The lamina densa of the glomerular basement membrane
e. The epithelial slit pore

A

e. The epithelial slit pore

40 Å is on the larger side of proteins that can be filtered - the large size of this protein matters more than any charge hindrance or hydrostatic forces that typically affect smaller proteins

23
Q

What are the characteristics of IgA nephropathy on…

LM

FM

EM

A

IgA nephropathy = nephritic

  • LM
    • Mesangial proliferation (hypercellularity)
  • FM
    • Granular IgA deposits in the mesangium
  • EM
    • Mesangial deposits
24
Q

How is membranous nephropathy treated?

A
  • Secondary: treat underlying cause (if presnt)
    • Solid tumor cancer treatment
    • Stop medication exposure
    • Treat Hep B or Hep C
    • Treat Lupus
  • Primary: Depends on degree of proteinuria
    • Low-level: RAAs blockade, Na+ restriction, diuresis
    • High-level: Immune modulation
25
Q

Characteristic of nephritic or nephrotic syndrome?

Proteinuria >3 grams/day

A

Neprotic

26
Q

What defines nephrotic syndrome?

(Classic tetrad)

A
  • Proteinuria
  • Hypoalbuminemia
  • Edema
  • Hypercholesterolemia
27
Q

What is required for a diagnosis of lupus nephritis?

A

Kidney biopsy + History of lupus

28
Q

What are the major nephritic syndromes?

A
  • Immune Complex
    • IgA
    • PIGN
    • Lupus Nephritis
  • Pauci-Immune
    • ANCA-Associated GN (vasculitis, +P-ANCA, +C-ANCA)
  • Anti-GBM
29
Q

What tubular dysfunctions can cause proteinuria?

A
  • Dent disease
    • Disorder of chloride transport, cannot reabsorb protien
  • Fanconi syndrome
    • Nephropathic cystinosis
  • Tubulointerstitial nephritis
  • Nephrotoxins
30
Q

What are the 3 major primary nephrotic syndromes?

A

Minimal Change Diseae

Focal Segmental Glomerular Sclerosis

Membranous Nephropathy

31
Q

What are the characteristics of diabetic nephropathy on light microscopy?

A

Diffuse GBM thickening (leads to proteinuria)

Nodular sclerosis: Kimmelstiel-Wilson nodules

32
Q

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

A

Membranous nephropathy

33
Q

Which renal syndrome is associated with APOL1 mutation?

A

FSGS-nephrotic syndrome

(FSGS is a pattern of injury, not a renal syndrome, I just didn’t know how else to phrase the question)

34
Q

What are the characteristics of Membranous Nepropathy on..

LM:

FM:

EM:

A

Membranous nephropathy = nephrotic

  • LM
    • Thickened capillary wall (Wire-Loop)
    • Thickened GBM
    • Spikes and holes on silver stain
  • FM
    • Granular IgG and C3 deposits in the basement membrane
  • EM
    • Sub-epithelial immune deposits
    • Spike and dome pattern
35
Q

Match the image to the correct renal syndrome:

IgA Nephropathy

Anti-GBM Disease

A

A = Anti-GBM disease

  • Linear deposits along the GBM
  • Expect these to be IgG

B = IgA nephropathy

  • Granular dposits in the mesangium
  • Expect these to be IgA

Both are nephritic syndromes

36
Q

How does podocyte effacement affect filtration of larger macromolecules?

A

Effacement decreases the available filtration surface area

This leads to decreased filtration of larger marcomolecules

Note: Loss of negative charges = more albumin gets through

(But less of other proteins due to decreased surface area)

37
Q

Which glomerular nephritis is most common worldwide?

A

IgA Nephropathy

38
Q

Which nephrotic syndromes result from primary podocytopathy?

A

Minimal change disease (MCD)

Focal Segmental Glomerulosclerosis (FSGS)

39
Q

What are the characteristics of RPGN on light microscopy?

A

Diffuse, crescenteric glomererulonephritis affecting >50% of all glomeruli

40
Q

Describe the key differences betwee Class IV Lupus Nephritis and Class V Lupus Nephritis

A
  • Class IV
    • Nephritic
    • Low serum complement
    • Cell proliferation, wire loops
  • Class V
    • Nephrotic (Yes, very confusing)
    • Normal serum complement
    • Thickened GBM, spike and dome pattern
      • Like membranous nephropathy
41
Q

What are the characteristics of FSGS on..

LM:

FM:

EM:

A

FSGS = nephrotic

  • LM
    • 1 or more lesions of segmental sclerosis
    • Not all glomeruli involved
    • Only a portion of each involved glomerulus is affected
  • FM: nonspecific
  • EM
    • Podocyte effacement

Note: FSGS is a pattern of injury

May be idiopathic, drug induced, or a complication of other diseaes

42
Q

How can nephrotic syndrome lead to hypercoagulability?

A
  • Possible loss of anticoagulants in the urine
  • Increased platelet aggregation: albumin is a carrier protein
  • Altered fibrinolysis
  • Glycoprotein charge on platelet and vessel wall
  • Hemoconcentration, dehydration, steroids
43
Q

Class V Lupus Nephritis presents like which renal syndrome?

A

Membranous nephropathy (nephrotic)

  • LM
    • Thickened GBM
    • Spike and hole pattern on silver stain
  • FM
    • Full House
  • EM
    • Sub-epithelial immune deposits
    • Spike and dome pattern
  • Normal serum complement
44
Q

Which proteins are necessary for reabsorbing protein in the kidney tubule?

A

Megalin

Cubulin

Amnnionless (in clathrin-coated pits)

Failure of these proteins -> Proteinuria

45
Q

What is ANCA?

What are the relevant types?

A

Anti-neutrophil cytoplasmic antibodies

An autoimmune phenomenon

Present in Pauci-immune disease, a nephritic syndrome
(RPGN Type III)

  • p-ANCA = antibody against myeloperoxidase
  • c-ANCA = antibody against proteinase 3
  • X-ANCA = atypical ANCA
46
Q

Describe the characteristics of MPGN on…

LM

FM

EM

A

MPGN = Nephritic

  • LM
    • Lobular glomerulus (shown in picture)
    • Hypercellular
    • Tram-Tracking on silver stain
  • FM
    • Granular C3 deposits (+/- IgG) in the Basement Membrane
  • EM
    • Variable
47
Q

Characteristic of nephritic or nephrotic syndrome?

Edema, hyperlipidemia, and hypoalbuminemia

A

Nephrotic syndrome

48
Q

Characteristic of nephritis or nephrosis?

Normal heart and pleural fluid

A

Nephrosis

49
Q

How does nephrosis affect protein homeostasis?

A
  • Loss of plasma protein in the urine ->
  • -> Decreased levels of plasma proteins
  • -> peripheral edema, metabolic abnormalities
50
Q

Which two renal syndromes cause foot process effacement?

A

Both nephrotic

  • Minimal change disease
    • More likely in children than adults
    • No changes on LM or FM
  • Focal segmental glomerulosclerosis
    • More likely in adults than children
    • Focal segmental sclerosis on LM
      • 1 or more lesions
    • FM shows non-specific staining
51
Q

Whch renal syndrome shows “tram tracking” on silver stain?

A

MPGN (Nephritic)

52
Q

What are the characteristics of Minimal Change Disease on..

LM:

FM:

EM:

A

Minimal change disease = Nephrotic

  • LM: No changes
  • FM: No changes
  • EM: Podocyte effacement

Usually responds well to steroid treatment

53
Q

How is FSGS treated?

A

Challenging

Start with steroids - Usuallly not responsive, use calcineurin inhibitor or Cellcept next

Treat secondary cause if possible

54
Q

How does fluid overload affect glomerular macromolecule handling?

A

Increased proteinuria

Filtration equilibrium is not yet reached - Increaed overall filtration, drags proteins across the filtration barrier

55
Q

How can you use serum and urinary levels of beta2-Microglobulin to differentiate between tubular and glomerular dysfunction?

Note - beta2-Microglobulin is usually freely filtered by the glomerulus and reabsorbed in the proximal tubule

A
  • If glomerular dysfunction
    • High serum beta2-Microglobulin
    • Low urinary beta2-Microglobulin
  • If tubular dysfunction
    • Low serum beta2-Microglobulin
    • High urinary beta2-Microglobulin
56
Q

What are the characteristics fo Pauci-Immune disease on…

LM

FM

EM

A

Pauci-Immune disease = RPGN Type III - Nephritic

ANCA will show up on labs

  • LM
    • Fibrinoid necrosis (necrotizing vasculidities)
    • Diffuse, crescenteric glomerulonephritis affecting >50% of glomeruli
  • FM
    • No depositis
  • EM
    • No deposits
57
Q

A 12 year old patient presents with sudden-onset edema and 4 g/day proteinuria.

Renal biopsy shows no findings on LM or FM, but their EM is shown below:

What is the most likely diagnosis?

A

Minimal change disease

58
Q

Which renal syndrome is characterized by a “spike and dome” pattern on EM?

A

Membranous nephropathy (nephrotic syndrome)

59
Q

What is the best correlation for hypercoagulability in nephrotic syndrome?

A

Decreased circulating free protein S

Less free protein S = more hypercoagulable

60
Q

What are the characteristics of Anti-GBM disease on…

LM:

FM:

EM:

A

Anti-GBM = RPGN Type I = Nephritic

  • LM
    • Diffuse, crescenteric GN affecting >50% of glomeruli
  • FM
    • Linear IgG deposits
  • EM
    • No distinct deposits - evenly distributed
61
Q

Characteristic of nephritis or nephrosis?

Increased intravsascular volume

A

Nephritis

62
Q

What are the characteristics of Post-Infectious Glomerulonephritis on…

LM

FM

EM

A

PIGN = Nephritic syndrome

  • LM
    • Hypercellularity - Neutrophils, lymphocytes
  • FM
    • Granular
    • IgG and complement
  • EM
    • Sub-epithelial humps
63
Q

Characteristic of nephritis or nephrosis?

Hypertension

A

Nephritis (usually)

(Nephrosis sometimes)

64
Q

Nephritic syndrome is a clinical sequalae of __________

A

Nephritic syndrome is a clinical sequalae of glomerular inflammation

65
Q

Why is plasmapheresis used to treated Anti-GBM Disease?

A

Remove immune complexes from the blood to prevent further damage to the GBM

(Plasmapheresis = remove patient’s plasma, replace it with other plasma)

66
Q

Why are vomiting and diarrhea especially worrisome in nephrotic syndrome?

A

Can lead to low effective blood volume, which is easily missed in the setting of edema

67
Q

What causes tubulointerstitial nephritis?

A
  • Infections
    • Acute pyelonephritis
    • Chronic pyelonephritis and reflux nephropathy
  • Drug-induced
    • Analgesics
    • Caffeine
  • Ischemia
  • Metabolic derangements
  • Physical damage
68
Q

Characteristic of nephritis or nephrosis?

Decreased GFR

A

Nephritis

69
Q

Characteristic of nephritic or nephrotic syndrome?

RBCs, RBC casts

A

Nephritic

70
Q

What are the requirements for diagnosis of FSGS?

A

Kidney biopsy showing…

  • Focal segmental sclerosis
    • Focal = not all glomeruli are involved
    • Segmental = only a portion of the involved glomeruli are affected
  • 1 or more lesions of segmental sclerosis on light microscopy
  • Foot process effacement on electron microscopy
71
Q

What are the two proposed mechanisms for edema formation in nephrotic syndrome?

A
  • Underfilling (traditional) model - Driven by Starling forces
    • Loss of serum proteins
    • -> Decreased oncotic force in the capillaries
    • -> Increased movement of fluid from capillaries -> interstitium
    • -> Vascular volume contraction (they are underfilled)
    • -> Decreaed glomerular perfusion
    • -> Increased renin secretion
    • -> Thirst, aldosterone, increased Na+ reabsorption
  • Overfilling model
    • Primary Na+ retention drives edema
    • In this case, aldosterone and renin would be low
72
Q

How does dehydration affect glomerular macromolecule handling?

A

Increaesd proteinuria due to increased concentration of proteins in the filtrate

73
Q

Characteristic of nephritis or nephrosis?

Renal inflammation

A

Nephritis

74
Q

A patient presents with purpura, ulcers, and flu-like symptoms.

Urinalysis shows RBCs and RBC casts

LM shows fibrinoid necrosis and crescenteric glomerulonephritis affecting >50% of glomeruli

FM and EM are unremarkable

Which renal syndrome is most likely?

A

Nephritic

Pauci-Immune disease (RPGN Type III)

75
Q

What is the treatment for Anti-GBM disease?

A

Aggressive treatment!

Steroids + Cyclophosphamide + Plasmapheresis

76
Q

An extremely edematous child is seen in the emergency ward for relapse of known minimal change nephrotic syndrome.

What are the benefits and problems in treating the edema with furosemide?

A
  • Benefits
    • Furosemide will effetively diurese the patient
    • Interrupt the viscious cycle of nephrotic Na+ retention
  • Potential problems
    • Less effective if renal perfusion in is poor
    • If low EBV is missed and furosemide is given, further volume depletion could cause death
    • May exacerbate hemoconcentration
      • -> Thrombosis
    • Wastes total body K+ stores
77
Q

How does nephrotic syndrome affect bone metabolism?

A

Loss of Vitamin D binding protein and Vitamin D metabolites in the urine

  • Usually reabsorbed by megalin, but it is busy trying to reabsorb albumin
  • -> Decreased Ca2+ absorption
  • -> Increased PTH (due to low Ca2+)
78
Q

What is the pathologic finding assoicated with diabetic nephropathy?

A

Kimmelstiel-Wilson Nodules

(Nodular sclerosis)

79
Q

Which renal syndrome will have ANCAs?

A

Pauci-Immune Disease (aka RPGN Type III)

  • Neprhitic
  • ANCA = Anti-neutrophil cytoplasmic antibody
    • p-ANCA = antibody against myeloperoxidase
    • c-ANCA = antibody against proteinase 3
80
Q

Characteristic of nephritis or nephrosis?

Cardiomegaly + pulmonary edema

A

Nephritis