Lecture 9 - Glomerular Diseases Pathology

Question 1

What is a glomerulus made from?

Answer 1

Capillary loops

Question 2

What size of protein will not be filtered in the glomerulus and will stay in the plasma?

Answer 2

All protein equal to or larger than albumin (incl. Ig)

Question 3

What do the podocytes have?

Answer 3

Foot processes that hold on to the capillary

Question 4

What are the 3 layers of the walls of the capillaries in the glomerulus?

Answer 4

Endothelial cell cytoplasm, basal lamina, podocytes

Question 5

What mesangial cells?

Answer 5

Tree like group of cells that support the capillaries

Question 6

Where does the filtrate coming from the glomerulus go?

Answer 6

Into Bowman’s space and then into the proximal tubule

Question 7

Where do blood cells, some fluid, albumin and larger proteins exit the glomerulus?

Answer 7

Via the efferent arteriole

Question 8

What is a glomerulonephritis?

Answer 8

A disease of the glomerulus

Question 9

What are the two broad types of GNs?

Answer 9

Those due to Ig deposition

Those not due to Ig deposition, e.g. diabetic glomerular disease

Question 10

What are the four common presentations of GN?

Answer 10

Haematuria
Heavy proteinuria (nephrotic syndrome)
Slowly increasing proteinuria
Acute renal failure

Question 11

What are the 3 most common causes of haematuria?

Answer 11

UTI
Urinary tract stone
Urinary tract tumour

GNs more uncommon (exclude top 3 first)

Question 12

What should you always do before taking a renal biopsy?

Answer 12

Check clotting as kidneys are v. vascular and can bleed to death

Question 13

In IgA nephropathy does IgA get filtered into urine?

Answer 13

No it gets stuck in the mesangium and causes mesangial proliferation

Question 14

It is the mesangium and not the filter membrane that becomes clogged with IgA so why does this cause disease lead to haematuria?

Answer 14

IgA irritates mesangial cells and causes them to proliferate and produce more matrix

Question 15

What can you see on light microscopy in membranous GN?

Answer 15

Thickened glomerular basement membrane

Question 16

What can you see on electron microscopy in membranous GN?

Answer 16

Spikes of new basement membrane matrix material under podocytes
Deposits of Ig

Question 17

Where is the IgG stuck in membranous GN?

Answer 17

It is deposited in the basal lamina and podocyte but cannot be filtered into urine

Question 18

What happens after the IgG is stuck in the membrane in membranous GN?

Answer 18

Activates C3 which punches holes in the membrane –> leaky filter now allows albumin to be filtered into urine –> nephrotic syndrome

Question 19

What is the underlying cause of IgG production and accumulation in membranous GN?

Answer 19

Unknown, sometimes linked to underlying malignancy

In many pts antigen is phospholipase A2 receptor (unknown why)

Question 20

What is the pathophysiology of diabetic glomerular disease?

Answer 20

Glycated molecules –> matrix deposition in basal lamina underlying endothelial + in mesangial matrix –> thickened by leaky basement membranes + messengial matrix compresses capillaries

Question 21

Who is diabetic glomerular disease seen in?

Answer 21

Those with poor diabetic control

Question 22

What do you see on histology in diabetic nephropathy?

Answer 22

Small compressed capillary lumen
Adhesions to Bowman’s capsule as an attempt to stop albumin leakage
Thickened capillary wall which is leaking albumin
Increased mesangial matrix –> compresses capillaries
Thickened, narrowed arterioles reduce BF to glomerulus

Question 23

What nodules do you see in diabetic nephropathy?

Answer 23

Kimmelsteil-Wilson nodules (gross excess of mesangial matrix forming nodules)

Question 24

What things will lead to an inevitable decline of a diabetic nephropathy?

Answer 24

Established diabetic nephropathy

Continued poor diabetic control

Question 25

What can cause crescentic GN?

Answer 25

Wegener’s

Microscopic polyarteritis etc.

Question 26

Explain how ANCA cause kidney damage in Wegener’s despite not being deposited in the kidney?

Answer 26

These antibodies produce tissue damage via interactions with primed neutrophils and endothelial cells

Question 27

What drug leads to a 75% remission rate in Wegener’s?

Answer 27

Cyclophosphamide