PATH: Glomerular Structure

Question 1

What are the 4 main components of the glomerulus?

Answer 1

Podocytes
GBM
Endothelium
Mesangium

Question 2

What makes up the slit-pore diaphragm?

Answer 2

Cadherin and F.A.T. (bind adjacent pediceles)

Nephrin and Podocin (role in filtration)

Question 3

List the 3 parts of the GBM.

Answer 3

Lamina lucida (rara interna)
Lamina densa
Lamina rara exerna

Question 4

List the components of the GBM.

Answer 4

Type 4 collagen (major)
Perlecan
Entactin
Laminin
Fibronectin
Integrins

Question 5

What is the role of perlecan in the GBM?

Answer 5

highly negatively charged proteoglycan containing heparin sulfate–gives GBM its negative charge to repel proteins

Question 6

What is the role of entactin?

Answer 6

glycoprotein with Ca2+ binding properties

Question 7

What is common amongst the secondary glomerular diseases?

Answer 7

they are systemic diseases (ex. diabetes, lupus, HTN) that involve multiple organs

Question 8

List the 3 most common types of glomerular diseases.

Answer 8

Hemodynamic (Hypertensive)
Metabolic (Diabetic)
Immune-mediated

Question 9

Infectious glomerular diseases typically involve what part of the glomerulus?

Answer 9

interstitium

Question 10

Toxic glomerular diseases typically involve what part of the glomerulus?

Answer 10

tubules

Question 11

Where do neoplasms that lead to glomerular disease arise?

Answer 11

tubular epithelium (DO NOT occur in the glomeruli)

Question 12

List the 4 roles of the mesangium.

Answer 12

1) phagocytosis
2) contraction
3) support
4) secretion of mesangial matrix

Question 13

True or false: hydrostatic pressure in glomerular capillaries is higher than other capillaries.

Answer 13

TRUE: must be higher to drive filtration

Question 14

What happens if glomerular capillary hydrostatic pressure increases too much (like in malignant hypertension)?

Answer 14

HYALINE SCLEROSIS OF THE AFFERENT ARTERIOLE: Capillaries injured–> GBM thickens–> mesangial cell hypertrophy and hyperplasia

Question 15

What is the result of hyaline sclerosis of the afferent arteriole in malignant HTN?

Answer 15

ARTERIONEPHROSCLEROSIS: Lumen narrows until ischemic atrophy of the glomerulus occurs–> global sclerosis

Question 16

Describe the feedback loop formed with malignant HTN and arterionephrosclerosis.

Answer 16

HTN causes ischemic atrophy of glomerulus–> Arterionephrosclerosis decreases the number of functioning nephrons–> decrease GFR–> R-A-A system –> HTN

Question 17

Why do African Americans more commonly get arterionephrosclerosis from HTN?

Answer 17

Variant gene for ApoL1 that prevents trypanosomal protein from inhibiting the lysis of parasites that cause African Sleeping Sickness

Question 18

What are anti-GBM antibodies against?

Answer 18

alpha 3 chain of type IV collagen in the glomerular and alveolar basement membranes

Question 19

What are the s/s of Goodpasture syndrome?

Answer 19

Hematuria and hemoptysis

Question 20

Where are the anti-GBM antibodies deposited in the glomerulus?

Answer 20

subendothelial

Question 21

What all is deposited in anti-GBM disease?

Answer 21

IgG and C3 (with the anti-GBM antibody)

Question 22

What does the light, IF, and EM look like in anti-GBM disease?

Answer 22

Light: crescents
IF: linear
EM: normal

Question 23

What causes crescentic glomerulonephritis?

Answer 23

Effacement of foot processes and detachment will occur during nephritic syndrome—allowing GBM to be degraded. Plasma proteins (with Ab’s, inflammatory cytokines, etc.) leak out into Bowman’s Space and create crescent-shaped areas of inflammation with proliferation of parietal epithelial cells

Question 24

What is mutated in slit pore diaphragm disease?

Answer 24

Nephrin and Podocin (glycoproteins that maintain selective permeability of glomerular filtration barrier).

Question 25

What are the two “forms” of immune complexes?

Answer 25

ICs deposited from the circulation

ICs that form “in situ” with fixed antigens

Question 26

How do immune complexes cause injury?

Answer 26

1) Direct cytotoxic action
2) Activation of leukocytes/complement cascade
3) Leakage of lysosomal proteases/ROS/etc. to reduce GFR and allow platelet aggregation (with help from endothelial cells secreting IL-1, growth factors, etc.)

Question 27

Where are the 3 places immune complexes can deposit?

Answer 27

1) Subepithelial (if from in-situ complexes)
2) Subendothelial (usually, ICs cannot cross the GBM–> leads to “wire loops”)
3) Mesangial

Question 28

Proteinuria is usually caused by glomerular diseases that target what?

Answer 28

podocytes, slit diaphragm, or subepithelium

Question 29

Hematuria is usually caused by glomerular diseases that target what?

Answer 29

capillary endothelium or subendothelium

Question 30

Glomerular diseases that target what part of the glomerulus tend to be worse?

Answer 30

the capillary side of the glomerulus!

Question 31

Hyperglycemia has what initial effect on the kidney?

Answer 31

first will increase GFR and size due to hyperfiltration–> but over time this will lead to increased pressure, injury, and hypertrophy which injures the glomerulus and causes a drop in GFR

Question 32

Over time, what can happen in the kidneys of diabetics with high blood sugar?

Answer 32

Non-enzymatic glycosylation of proteins in the blood and GBM. The blood proteins “stick” to the GBM proteins and increase rate of produciton of GBM proteins, thickening and distorting GBM.

Question 33

What mediators stimulate NADPH oxidase to cause damage and proteinuria in diabetic nephropathy?

Answer 33

AOPP, AGE, R-A-A system, and TGF-beta