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Renal > Glomerular Structure & Mech of Disease (Nichols) > Flashcards

Glomerular Structure & Mech of Disease (Nichols) Flashcards

1
Q

What is the glomerulus?

A

Renal filter for liquid portion of blood

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2
Q

What glomerular component stains black?

A

Basement membrane

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3
Q

What glomerular component stains white?

A

Bowmans space

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4
Q

What glomerular component stains pink?

A

Endothelial cells and Epithelial cells

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5
Q

Is the GBM significantly thicker in men or women? Who is anti- GBM disease more common in?

A

Men, especially young, especially white

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6
Q

What completely covers the outer surface of the capillary (facing the urinary space)

A

Interdigitating podocytes pedicles

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7
Q

What is the outer surface ofthe capillary(thats facing the urinary space) completely covered by ?

This picture of glomerularcapillary loop reveales what just below the red arrow?

A

Interdigitating podocyte pedicles

Fenestrations

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8
Q

What’s green?

What’s yellow?

What’s purple?

What’s blue?

A

Green:
Podocytes &
foot processes

Yellow:
Basement
membrane

Purple:
Endothelium

Stippled black
& blue:
Mesangium

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9
Q

How much of the capillary surface may correspond to fenestrations?

A

Up to 50%

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10
Q

What facilitates filtration and
accessibility of macromolecules (including antibodies*)
to glomerular basement membrane

A

The lack of a continuous cytoplasmic barrier

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11
Q

Podocytes cover the capillaries with an extensive network of ?

A

Cell processes-Pediceles

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12
Q

What are the visceral epithelial cells called?

A

Podocytes

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13
Q

Podocytes are in a layer that is continuous with what?

A

Parietal cells

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14
Q

The parietal cells are continuous with the podoctyes and what?

A

With the cells lining the proxmial tubule

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15
Q

What structure is found between the pediceles and connects them?

A

Slit pore diaphragm

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16
Q

What are conditions called that cause severe loss of protein through the glomeruli?

A

Nephrotic syndrome

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17
Q

What is effacement?

A

A retraction of foot processes and loss of slit pore diaphragm. On EM, it looks like fusion of foot processes

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18
Q

What also occurs in nephrotic syndrome in addition to effacement?

A

Detachment of
foot processes from the basement membrane and
degradation of glomerular basement membrane
allowing plasma proteins to leak into the urinary
space.

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19
Q

How many lamina does the glomerular basement membrane have?

A

Three. It’s a trilaminar structure

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20
Q

At the level of the lamina densa, of two basement membranes:

This structure of the basement
membrane represents the embryologic fusion,

A

Endothelial and epithelial

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21
Q

The minimal space between two pediceles is called?

A

Filtration slit

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22
Q

The thin structure bridging that space b/w two pediceles is?

A

Slit pore diaphragm

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23
Q

The slit pore diaphragm contains what?

A

Mutliple types of protein all secreted by podocytes

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24
Q

Some slit pore diaphragm proteins such as cadherin and FAT serve what purpose?

A

Bind adjacent pediceles

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25
Q

Some slit pore diaphragm proteins, such as nephrin and podocin, play a role in what?

A

Filtration

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26
Q

Mutations in the nephrin and podocin genes result in?

A

Congenital nephrotic syndromes due to the loss of large amounts of protein in the urine from the defective slit pore
diaphragm filtration.

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27
Q

What is the major component of the glomerular basement membrane?

A

Type IV collagen

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28
Q

What are the other 3 major components of the basement membrane?

A

Perlecan, entactin, and laminin

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29
Q

What is perlecan?

A

A highly charged proteoglycan containing heparan sulfate; it imparts most of the charge properties of basement membranes

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30
Q

What is entactin?

A

A glycoprotein with calcium binding properties

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31
Q

What is laminin?

A

A family of complex glycoproteins formed by three different chains.

32
Q

Most of the alpha chains are in what characteristic conformation?

A

Helical. But there is a non-helical globular domain, which is called a “non-collagenous” (NC) domain

33
Q

There are diseases caused by antibodies against an epitope in the NC1 domain of the alpha3 (IV) chain which cause?

A

Glomerulonephritis with hematuria (and pulmonary hemorrhage with hemoptysis, in about half of the patients

Goodpasture syndrome

34
Q

What provides structural support to the glomerulus?

A

Glomerular mesangial cells and their matrix provide structural support to the glomerulus

35
Q

Mesangial cells are mesenchymal cells with what properties?

A

With phagocytic and contractile properties; they’re equivalent to pericytes around other capillaries

36
Q

What happens to substances like antibodies that reach mesangial cells?

A

Phagocytosed by mesangial cells

37
Q

What are the three most common mechanisms of glomerular disease?

A

Immune-mediated
Metabolic
Hemodynamic

38
Q

Many glomerular diseases are caused by what?

A

Antibodies and immune complex deposition

39
Q

Immune complexes can be deposited from what two places?

A

From the circulation or in situ

40
Q

In situ antibodies can be directed against what types of antigens?

A

Intrinsic (fixed) antigens or planted (antigens in the bloodstream)

41
Q

What occurs in lupus nephritis?

A

Large circulating immune complexes
typically cannot pass through the GBM
and get stuck in a subendothelial
location

42
Q

What occurs in Goodpasture syndrome?

A

Circulating antibodies against the GBM deposit in a subendothelial location and in a linear pattern all along the GBM.

43
Q

What is used to detect antibody or complement deposition in glomeruli?

A

Immunofluorescence

44
Q

Immune complexes tend to be deposited in clumps and have what kind of pattern?

A

Granular

45
Q

Because the anti-GBM antibodies circulate before they are deposited, they can be treated how?

A

Plasma exchange

46
Q

What occurs in membranous nephropathy?

A

Circulating antibodies against antigens in the cell membrane of podocytes deposit outside the GBM and injure podocytes

47
Q

What is post-streptococcal glomerulonephritis?

A

An immune complex disease with antibodies apparently against streptococcal exotxin B, streptococcal GAPDH and endostroptosin

48
Q

In post streptococcal glomerulonephritis, the immune complexes form what in EM?

A

Subepithelial “humps” which correspond to granular deposits on immunofluorescence.

49
Q

What can rarely cause membranous nephropathy?

A

Antigens and antibodies that arrive separately and form complexes in a subepithelial location

50
Q

What is Metabolic (diabetic) glomerular injury?

A

Hyperglycemia causes non-enzymatic glycosylation of proteins in blood and in GBM

51
Q

In metabolic (diabetic) glomerular injury, what happens with some of the glycosylated plasma proteins?

A

They get trapped in the GBM along with the glycosylated native proteins, stimulating production of new GBM protein

52
Q

What’s the eventual result of metabolic (diabetic) glomerular injury?

A

A thickened GBM distorted by glycosylated proteins (some further metabolized to advanced glycation end-products [AGE] that mediate some of the accelerated aging that characterizes the effect of diabetes on organs throughout the body.)

53
Q

What activates NADPH oxidase?

A

Advanced oxidation protein products [AOPP], the renal angiotensin system, TGF-beta and AGEs

54
Q

Activated NADPH produces ROS, which causes what?

A

Mesagial matrix production, podocyte injury, apoptosis, and proteinuria

55
Q

What is Hemodynamic Glomerular Injury?

A
56
Q

The difference in pressure in hemodynamic glomerular injury drives what?

A

Drives filtration, but supra-normal glomerular capillary pressures injure them, stimulating GBM thickening (green) and
mesangial cell hypertrophy and hyperplasia and mesangial matrix production

57
Q

High blood pressure causes hyaline sclerosis to which arterioles of the glomeruli?

A

The afferent arterioles only.

58
Q

What changes occur as a result of hyaline sclerosis?

A

Plasma leaks into the wall and gradually narrows the lumen. This is followed by gradual ischemic atrophy of the glomerulus.

59
Q

HTN eventually results in what?

A

Globally sclerotic glomeruli

60
Q

What is the term for end stage HTN neuropathy?

A

ARTERIONEPHROSCLEROSIS

61
Q

Why is Arterionephrosclerosis 8 times more common in African Americans?

A

There are mutations in the gene for apoliporotein L1
unique to Africans conferring resistance to african sleeping sickness because the variant apoL1 does not bind a trypanosomal protein that blocks the action of a complex including apoL1, which lyses the parasites, as a function of innate immunity

62
Q

How does malignant HTN usually present?

A

Usually presents with blood pressure >200/120 mm Hg, headache, vomiting, proteinuria, hematuria, scotomas (“spots before the eyes”) and renal failure, especially in youngish black males around age 40?

63
Q

What does malignant HTN do?

A

Produces fibrinoid necrosis of arterioles (far end of spectrum with hyaline sclerosis) leading to necrosis of glomeruli.

64
Q

Malignant hypertension also produces what?

A

Proliferation of intimal cells in small arteries, hyperplastic arteriosclerosis, giving them an onion-skin appearance.

65
Q

Are hyperplastic arteriosclerosis and arterial fibrinoid necrosis specific for malignant hypertension?

A

No

66
Q

What is flea bitten kidney?

A

Small arteries and arterioles damaged by malignant hypertension

67
Q

Can malignant hypertension be fatal?

A

Yes.

68
Q

Kidney biopsies are unique because they require what three types of microscopy?

A

Light microscopy, immunofluorescence, and electron microscopy

69
Q

What does diffuse mean?

A

Involving all or most of the glomeruli

70
Q

What does focal mean?

A

Involving some but not most of the glomeruli

71
Q

What does global mean?

A

Involving the whole glomerulus

72
Q

What does segmental mean?

A

Involving only part of a glomerulus

73
Q

In glomerular disease, what does proliferative mean?

A

Increased cells: both native cell proliferation and or increases infltrating inflammatory cells

74
Q

What does membranous mean?

A

Increased GBM, without increases cells

75
Q

What is MPGN?

A

Membrano-proliferative

76
Q

What is Crescentic (glomerulonephritis)?

A

Disease involving Bowman space with proliferating parietal epithelial cells and infiltrating macrophages

77
Q
A

Renal (33 decks)

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