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Nephrology > Glomerular Structure and Mechanisms of Disease > Flashcards

Glomerular Structure and Mechanisms of Disease Flashcards

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1
Q

Name 9 places in a glomerulus that disease can be located.

A
  1. Arterioles 2. Capillaries
  2. Subendothelial 4. GBM
  3. Subepithelial 6. Slit pore diaphragm
  4. Podocytes 8. Bowman space/capsule
  5. Mesangium
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2
Q

Name 8 primary glomerular diseases.

A
  1. Minimal change disease
  2. Focal segmental glomerulosclerosis
  3. Membranous nephropathy
  4. Acute post-streptococcal glomerulonephritis
  5. Membranoproliferative glomerulonephritis
  6. IgA nephropathy (Berger disease)
  7. Hereditary nephritis (Alport syndrome)
  8. Congenital nephrotic syndrome
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3
Q

Name 5 secondary glomerular diseases.

A
  1. Hypertensive nephropathy
  2. Diabetic nephropathy
  3. Lupus nephritis
  4. Amyloidosis
  5. Goodpasture syndrome
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4
Q

Name the three most common types of glomerular disease.

A
  1. Hypertensive
  2. Diabetic
  3. Immune-mediated
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5
Q

What do supra-normal glomerular capillary pressures result in?

A

GBM thickening
Mesangial cell hypertrophy/hyperplasia,
Mesangial matrix production
Hyaline sclerosis of afferent arterioles

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6
Q

What is the term for global sclerosis of glomeruli?

A

Arterionephrosclerosis

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7
Q

Why is arterionephrosclerosis more common in African Americans?

A

Mutation of apolipoprotein L1 (normally confers Trypanosoma resistance)

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8
Q

What two conditions are a mutation in apoL1 associated with?

A

Arterionephrosclerosis

Focal segmental glomerulosclerosis

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9
Q

What are the symptoms/signs of malignant hypertension?

A 
BP > 200/120
Headache
Hematuria / Proteinuria
Scotomas
Vomitting
Onion-skin appearance (proliferation of intimal cells in arteries; hyperplastic arteriosclerosis)
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10
Q

What does malignant hypertension produce?

A

Fibrinoid necrosis of arterioles

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11
Q

What category of disease does injury to glomerular capillary endothelium cause?

A

Thrombotic microangiopathies

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12
Q

What are the layers of the glomerular basement membrane?

A 
Lamina rara (or lucida) interna
Lamina densa (double usual thickness)
Lamina rara externa
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13
Q

What are the major components of the basement membrane?

A 
Type IV collagen
Perlecan
Entactin
Fibronectin
Laminin
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14
Q

What is the composition and function of perlecan?

A

Highly charged proteoglycan w/ heparan sulfate keeps proteins (ie albumin) from being filtered

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15
Q

What is the function of entactin?

A

Glycoprotein with calcium binding properties

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16
Q

What is the function of fibronectin?

A

Glycoprotein binds collagen, heparan sulfate, and integrins

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17
Q

What is the function of laminin?

A

Binds collagen, entactin, heparan sulfate, and cells (integrins)

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18
Q

What heterotrimers are present in adult type IV collagen?

A

alpha3, alpha4, alpha5

alpha5, alpha5, alpha6

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19
Q

What is a cause of glomerulonephritis with hematuria?

A

Antibody against epitope in the NC1 domain of the alpha3 chain

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20
Q

Which gender has a thicker glomerular basement membrane?

21
Q

Which gender has a higher incidence of anti-GBM disease?

22
Q

What happens to podocytes during nephrotic syndrome?

23
Q

What causes crescentic glomerulonephritis and what is the pathology?

Study These Flashcards
A

Nephrotic syndrome with inflammatory stimuli lead to proliferation of parietal epithelial cells

24
Q

Name 4 proteins involved in the slit pore diaphragm.

Study These Flashcards
A

Cadherin and FAT - bind adjacent pedicles

Nephrin and podocin - play a role in filtration

25
What is a potential cause of congenital nephrotic syndromes?
Mutations in nephrin and podocin
26
What causes IgA nephropathy?
Reduced glycosylation in the hinge region of IgA1
27
What can IgA form immune complexes with?
IgA IgG Fibronectin CD89 (soluble IgA receptor)
28
What do the immune complexes bind to that triggers phagocytosis?
CD71 (transferrin receptor on mesangial cells)
29
What produces the injurious inflammation in IgA nephropathy?
Complement activation | 75% Alternative - 25% Lectin
30
Define deposited and in situ immune complexes.
Deposited - originated in circulation | In situ - formed in glomerulus
31
Define intrinsic and planted antigens.
Intrinsic - fixed in glomerulus | Planted - from circulation
32
What mechanisms typically cause damage in immune-mediated glomerular disease?
Complement activation and leukocyte mechanisms
33
How do leukocytes cause glomerular injury?
Lysosomal proteases ROS Arachidonic acid metabolites
34
How do platelets cause glomerular injury?
Aggregation | Arachidonic acid metabolites
35
How do endothelial cells cause glomerular injury?
``` Cytokines (IL-1) Arachidonic acid metabolites Growth factors Nitric oxide Endothelin ```
36
How do glomerular epithelial and mesangial cells cause glomerular injury?
Cytokines (IL-1) Arachidonic acid metabolites Growth factors
37
What is a hallmark histopathology of lupus nephritis?
Subendothelial deposits thickening capillary walls that resemble "wire loops."
38
What location do poststreptococcal glomerulonephritis antigens plant?
Subepithelium (characteristic "humps")
39
What do antibodies against phospholipase A2 receptors of podocytes cause?
Membranous glomerulonephritis
40
What are the antibodies in post-streptococcal glomerulonephritis against?
Streptococcal exotoxin B Streptococcal GAPDH Endostroptosin
41
What three forms of microscopy are needed to diagnose kidney immune complex disease?
Light microscopy Immunofluorescence Electron microscopy
42
What stains are used in light microscopy when studying immune glomerular disease?
H&E Jones methenamine silver (GBM) periodic acid Schiff (cytoplasmic inclusions) trichome (collagen)
43
The largest subset of crescentic glomerulonephritis is described as what?
Pauci-immune (typically ANCA+)
44
What are P-ANCA and C-ANCA associated with?
P-ANCA - microscopic polyangiitis or Churg-Strauss syndrome | C-ANCA - granulomatous with polyangiitis or Wegener's
45
What does hyperglycemia cause in the blood and GBM?
Glycosylation of proteins Thickening of GBM Deposits on GBM
46
What causes the characteristic effect of diabetes mellitus on organs throughout the body?
Metabolization of glycosylated proteins to advanced glycation end-products (AGE)
47
What activate/induce NADPH oxidases (producing ROS)?
Advanced glycation end-products (AGE) Advanced oxidation protein products (AOPP) Renin Angiotensin System (RAS) TGF-beta
48
What does activated NADPH oxidases (and ROS) cause in the kidney?
Mesangial cell hypertrophy / hyperplasia Mesangial matrix production Podocyte injury / apoptosis
49
What does hypertension cause in the glomerulus?
GBM thickening Mesangial cell hypertrophy / hyperplasia Mesangial matrix production

Nephrology (18 decks)

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