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Renal 2 > Path - Glomerular Structure and Mechanisms of Disease > Flashcards

Path - Glomerular Structure and Mechanisms of Disease Flashcards

1
Q

3 layers of Glomerulus?

A

Capillary to urinary space

  1. Fenestrated endothelium
  2. Glomerular basement membrane
  3. Pedicels (foot processes) on epithelium
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2
Q

Men or women have thicker glomerular basement membrane?

A

Men

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3
Q

glomerular basement membrane (GBM) disease more common in men?

A

Anti-GBM disease

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4
Q

What % of capillary surface may correspond with fenestrations?

A

Up to 50%

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5
Q

Relationship between podocytes and foot processes (pedicels)?

A

Each adjacent pedicel belongs to a single podocyte. Therefore, there is an extensive network covering capillaries

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6
Q

3 layers of the basement membrane?

A

Endothelium (capillary space) to epithelium (urinary space)

  1. Lamina lucida (rara)
  2. Lamina densa
  3. Lamina rara externa
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7
Q

Thickest layer of GBM?

A

Lamina densa (double the thickness of lamina rara)

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8
Q

Minimal space between 2 pedicels = ?

A

Filtration slit

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9
Q

Slit pore diaphragm = ?

A

thin structure bridging the space between two pedicels

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10
Q

4 main slit pore diaphragm proteins?

A

Cadherin, FAT, Nephrin, Podocin

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11
Q

2 slit pore diaphragm proteins involved with binding adjacent pedicels?

A

Cadherin, FAT

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12
Q

2 main slit pore diaphragm proteins involved with filtration?

A

Nephrin, Podocin

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13
Q

Major component of the glomerular basement membrane?

A

Type IV collagen

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14
Q

4 major components of glomerular basement membrane?

A

(PELT) = Perlecan, Entactin, Laminin, & type IV collagen

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15
Q

Significant component of perlecan and function of this component?

A

Perlecan contains heparan sulfate, producing the main negative charge of the GBM. This negative charge prevents albumin (also negatively charged) from permeating through GBM.

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16
Q

Entactin binds what ion?

A

Calcium

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17
Q

Laminin is formed of how many different chains?

A

3

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18
Q

How many different alpha chains form Type IV collagen family? How many chains needed to form a collagen molecule? Conclusion based on these numbers?

A

6 numbered alpha chains. 3 needed to form a collagen molecule. Therefore, there is significant variability in the composition of individual molecules and basement membranes.

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19
Q

What is a “non-collagenous” domain?

A

Most of the alpha chains of type IV collagen are in the characteristic helical conformation; however, “non-collagenous” domain = non-helical globular domain

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20
Q

antibodies attack what in Goodpasture syndrome?

A

antibodies attack NC1 (non-collagenous 1) domain of the alpha3 chain of Type IV collagen, causing glomerulonephritis with hematuria AND pulmonary hemorrhage with hemoptysis.

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21
Q

2 main clinical findings leading to Goodpasture syndrome?

A
  1. Glomerulonephritis with hematuria
  2. Pulmonary hemorrhage with hemoptysis

Need both clinical findings to be considered Goodpasture syndrome

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22
Q

3 main functions of mesangial cells?

A
  1. Structural support to glomerulus
  2. Phagocytic properties
  3. Contractile properties
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23
Q

Describe phagocytic properties of mesangial cells?

A

Mesangial cells within the mesangial matrix will trap antibodies and Antigen-antibody complexes and eventually phagocytose them.

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24
Q

3 most common mechanisms of glomerular disease?

A
  1. Immune-mediated
  2. Metabolic
  3. Hemodynamic
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25
Immune mediated glomerular disease are caused by?
1. antibodies, 2. immune complexes
26
Immune complexes involved in glomerular diseases can be present in what 2 forms?
Can be 1) deposited from the circulation or 2)form in situ
27
In situ antibodies (related to immune complexes of glomerular diseases) can be against what 2 types of antigens?
Can be against 1) intrinsic (fixed) antigens in the glomerulus or 2) "planted" antigens originally found in the bloodstream
28
Mechanism of "planted" antigens
Antigens and antibodies are floating in circulation. Antigen gets to glomerulus 1st, then antibody gets there and recognizes "planted" antigen
29
Describe immune complexes in lupus nephritis?
Large circulating immune complexes will pass through fenestrations of endothelium and get stuck in **subendothelial location** of GBM.
30
Immune complex of Lupus nephritis/SLE
Immune complexes deposited in **CLUMPS** and have a **GRANULAR PATTERN**
31
Goodpasture syndrome antibody feature?
Circulating antibodies against the GBM deposit in a subendothelial location **ALL ALONG** the GBM
32
Pattern of antibody deposition in Goodpasture syndrome?
**Linear pattern** all along the GBM
33
anti-GBM disease = ?
Considered half of good pasture syndrome, only involving the kidney
34
Treatment against anti-GBM antibodies? Why is this method of treatment effective?
Plasmapheresis. B/c the anti-GBM antibodies circulate before they are deposited within the glomerulus
35
Membranous nephropathy antibody feature?
Circulating antibodies against antigens in the cell membrane of podocytes deposit **OUTSIDE** the GBM and injure podocytes
36
Post-streptococcal glomerulonephritis = immune complex disease against ?
Primarily against streptococcal pyogenic exotoxin B
37
Immune complex deposition of post streptococcal glomerulonephritis = ?
**SUBEPITHELIAL "HUMPS"** with granular deposits (more granular than lupus granular deposits)
38
What metabolic disease causes glomerular injury?
Diabetes
39
Diabetes causes what to occur in proteins?
Non-enzymatic glycosolation of proteins
40
Which type of proteins are affected in diabetes (circulating or intrinsic to GBM)
Both. Glycosolation of both circulating proteins and intrinsic proteins of GBM can occur
41
In Diabetes, what happens to plasma and intrinsic proteins following glycosolation?
These proteins will get trapped in GBM, stimulating production of new GBM proteins.
42
What pathologic process is being shown here? Early or later stages?
Later stages in diabetes. After production of new GBM proteins (following glycosolation of plasma/intrinsic proteins), the GBM will eventually thicken, as shown in the picture. Advanced glycation end products (AGE) are produced (discussed on different notecard)
43
What are advanced glycation end products (AGE)?
In diabetes, some glycosylated proteins are further metabolized, forming AGE. These accelerate the effects that diabetes has on other organs = bad news.
44
List the 4 factors involved in progression to diabetic nephropathy? By what mechanism?
1) Advanced oxidation protein products [AOPP], 2) Renin-Angiotensin system, 3) TGF-beta, & 4) advanced glycation end products (AGEs) **activate NADPH oxidase**, producing ROS, causing mesangial matrix production, podocyte injury, apoptosis, and proteinuria. All these = diabetic nephropathy.
45
Hydrostatic pressure in glomerular capillary vs other capillaries?
Higher in glomerular capillary (50 mm Hg) vs usual 35 mmHg in other capillaries
46
Bowman's space pressure vs other capillary pressure?
Lower, roughly half (18 mm Hg) vs normal capillaries (35 mm Hg)
47
Increased hyrostatic pressure causes what 3 pathologic processes of glomerulus?
1. Stimulates GBM thickening 2. Mesangial cell hypertrophy and hyperplasia 3. Increased mesangial matrix production
48
HTN causes hyaline sclerosis of (afferent/efferent) arterioles?
Afferent arterioles. gradually narrows the lumen causing gradual ischemic atrophy of the glomerulus
49
End stage hypertensive nephropathy = ?
Arterionephrosclerosis
50
Arterionephrosclerosis more common in blacks or whites?
8x more common in blacks.
51
African sleeping sickness due to what bug?
Trypanosoma brucei rhodesiense
52
What mutation confers resistance to Trypanosomes in Africans? MOA?
Mutation in the gene for apolipoprotein L1, forming variant apolipoprotein L1. This variant doesnt bind trypanosomal protein, confering resistance to trypansosomes.
53
Malignant HTN classifed as what BP?
\>200/120 mmHg
54
Scotomas = what? = feature of what?
Scotoma - "spots before the eyes", feature of malignant HTN
55
2 common pathologic results of malignant HTN?
1. Fibrinoid necrosis 2. Hyperplastic arteriosclerosis
56
What is the pathophysiology of a "flea bitten kidney" ?
Malignant HTN damages small arteries and arterioles all over the kidney, giving it a "flea bitten" appearance
57
What is considered to be a medical emergency in terms of glomerular diseases?
**MALIGNANT HTN**
58
Kidney biopsies require what 3 types of microscopy?
1. Light microscopy 2. Immunofluorescence 3. Electron microscopy
59
Glomerular disease terminology. "involving all or most of the glomeruli" = ?
Diffuse
60
Glomerular disease terminology, "involving some but not most of the glomeruli" = ?
Focal
61
Glomerular disease terminology. "involving the whole glomerulus" = ?
Global = how much of 1 glomerulus
62
Glomerular disease terminology. "involving only part of the glomerulus" = ?
Segmental
63
Proliferative, Membranous, or Membranoproliferative? Definition of answer?
Proliferative. Increased # of cells (proliferative native cells, but also infiltrating inflammatory cells)
64
Proliferative, Membranous, or Membranoproliferative? Definition of answer?
Membranoproliferative = combination of membranous and proliferative (hence the name).
65
Proliferative, Membranous, or Membranoproliferative? Definition of answer?
Membraneous, increased GBM without increased # cells
66
3 features of crescentic glomerulonephritis?
1. Involves bowmans space 2. Proliferating epithelial cells 3. infiltrating macrophages
67
What is considered to be the largest subset of crescentic glomerulonephritis?
"pauci-immune" crescentic glomerulonephritis
68
P-ANCA is associated with what 2 pathologies?
Microscopic polyangiitis, Churg-Strauss syndrome
69
C-ANCA (antiproteinase 3) associated with what pathology?
Wegener's (granulomatous with polyangiitis)
70
fibrous scar replacing glomerulus = ?
glomerulosclerosis
71
fibrous scar replacing part of glomerulus = ?
Segmental glomerulosclerosis
72
Which is considered worse, acute necrotizing crescentic glomerulonephritis or focal segmental glomerulosclerosis? Why?
Acute necrotizing crescentic glomerulonephritis. If it involves bowman's space (as in crescentic) it means that disease has spread past the bloodstream into urinary space = bad news bears

Renal 2 (11 decks)

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