PATH: Glomerular Structure Flashcards
What are the 4 main components of the glomerulus?
Podocytes
GBM
Endothelium
Mesangium
What makes up the slit-pore diaphragm?
Cadherin and F.A.T. (bind adjacent pediceles)
Nephrin and Podocin (role in filtration)
List the 3 parts of the GBM.
Lamina lucida (rara interna)
Lamina densa
Lamina rara exerna
List the components of the GBM.
Type 4 collagen (major) Perlecan Entactin Laminin Fibronectin Integrins
What is the role of perlecan in the GBM?
highly negatively charged proteoglycan containing heparin sulfate–gives GBM its negative charge to repel proteins
What is the role of entactin?
glycoprotein with Ca2+ binding properties
What is common amongst the secondary glomerular diseases?
they are systemic diseases (ex. diabetes, lupus, HTN) that involve multiple organs
List the 3 most common types of glomerular diseases.
Hemodynamic (Hypertensive)
Metabolic (Diabetic)
Immune-mediated
Infectious glomerular diseases typically involve what part of the glomerulus?
interstitium
Toxic glomerular diseases typically involve what part of the glomerulus?
tubules
Where do neoplasms that lead to glomerular disease arise?
tubular epithelium (DO NOT occur in the glomeruli)
List the 4 roles of the mesangium.
1) phagocytosis
2) contraction
3) support
4) secretion of mesangial matrix
True or false: hydrostatic pressure in glomerular capillaries is higher than other capillaries.
TRUE: must be higher to drive filtration
What happens if glomerular capillary hydrostatic pressure increases too much (like in malignant hypertension)?
HYALINE SCLEROSIS OF THE AFFERENT ARTERIOLE: Capillaries injured–> GBM thickens–> mesangial cell hypertrophy and hyperplasia
What is the result of hyaline sclerosis of the afferent arteriole in malignant HTN?
ARTERIONEPHROSCLEROSIS: Lumen narrows until ischemic atrophy of the glomerulus occurs–> global sclerosis
Describe the feedback loop formed with malignant HTN and arterionephrosclerosis.
HTN causes ischemic atrophy of glomerulus–> Arterionephrosclerosis decreases the number of functioning nephrons–> decrease GFR–> R-A-A system –> HTN
Why do African Americans more commonly get arterionephrosclerosis from HTN?
Variant gene for ApoL1 that prevents trypanosomal protein from inhibiting the lysis of parasites that cause African Sleeping Sickness
What are anti-GBM antibodies against?
alpha 3 chain of type IV collagen in the glomerular and alveolar basement membranes
What are the s/s of Goodpasture syndrome?
Hematuria and hemoptysis
Where are the anti-GBM antibodies deposited in the glomerulus?
subendothelial
What all is deposited in anti-GBM disease?
IgG and C3 (with the anti-GBM antibody)
What does the light, IF, and EM look like in anti-GBM disease?
Light: crescents
IF: linear
EM: normal
What causes crescentic glomerulonephritis?
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
What is mutated in slit pore diaphragm disease?
Nephrin and Podocin (glycoproteins that maintain selective permeability of glomerular filtration barrier).
What are the two “forms” of immune complexes?
ICs deposited from the circulation
ICs that form “in situ” with fixed antigens
How do immune complexes cause injury?
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.)
Where are the 3 places immune complexes can deposit?
1) Subepithelial (if from in-situ complexes)
2) Subendothelial (usually, ICs cannot cross the GBM–> leads to “wire loops”)
3) Mesangial
Proteinuria is usually caused by glomerular diseases that target what?
podocytes, slit diaphragm, or subepithelium
Hematuria is usually caused by glomerular diseases that target what?
capillary endothelium or subendothelium
Glomerular diseases that target what part of the glomerulus tend to be worse?
the capillary side of the glomerulus!
Hyperglycemia has what initial effect on the kidney?
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
Over time, what can happen in the kidneys of diabetics with high blood sugar?
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.
What mediators stimulate NADPH oxidase to cause damage and proteinuria in diabetic nephropathy?
AOPP, AGE, R-A-A system, and TGF-beta
