Lecture 9 - Glomerular Diseases Pathology Flashcards
What is a glomerulus made from?
Capillary loops
What size of protein will not be filtered in the glomerulus and will stay in the plasma?
All protein equal to or larger than albumin (incl. Ig)
What do the podocytes have?
Foot processes that hold on to the capillary
What are the 3 layers of the walls of the capillaries in the glomerulus?
Endothelial cell cytoplasm, basal lamina, podocytes
What mesangial cells?
Tree like group of cells that support the capillaries
Where does the filtrate coming from the glomerulus go?
Into Bowman’s space and then into the proximal tubule
Where do blood cells, some fluid, albumin and larger proteins exit the glomerulus?
Via the efferent arteriole
What is a glomerulonephritis?
A disease of the glomerulus
What are the two broad types of GNs?
Those due to Ig deposition
Those not due to Ig deposition, e.g. diabetic glomerular disease
What are the four common presentations of GN?
Haematuria
Heavy proteinuria (nephrotic syndrome)
Slowly increasing proteinuria
Acute renal failure
What are the 3 most common causes of haematuria?
UTI
Urinary tract stone
Urinary tract tumour
GNs more uncommon (exclude top 3 first)
What should you always do before taking a renal biopsy?
Check clotting as kidneys are v. vascular and can bleed to death
In IgA nephropathy does IgA get filtered into urine?
No it gets stuck in the mesangium and causes mesangial proliferation
It is the mesangium and not the filter membrane that becomes clogged with IgA so why does this cause disease lead to haematuria?
IgA irritates mesangial cells and causes them to proliferate and produce more matrix
What can you see on light microscopy in membranous GN?
Thickened glomerular basement membrane
What can you see on electron microscopy in membranous GN?
Spikes of new basement membrane matrix material under podocytes
Deposits of Ig
Where is the IgG stuck in membranous GN?
It is deposited in the basal lamina and podocyte but cannot be filtered into urine
What happens after the IgG is stuck in the membrane in membranous GN?
Activates C3 which punches holes in the membrane –> leaky filter now allows albumin to be filtered into urine –> nephrotic syndrome
What is the underlying cause of IgG production and accumulation in membranous GN?
Unknown, sometimes linked to underlying malignancy
In many pts antigen is phospholipase A2 receptor (unknown why)
What is the pathophysiology of diabetic glomerular disease?
Glycated molecules –> matrix deposition in basal lamina underlying endothelial + in mesangial matrix –> thickened by leaky basement membranes + messengial matrix compresses capillaries
Who is diabetic glomerular disease seen in?
Those with poor diabetic control
What do you see on histology in diabetic nephropathy?
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
What nodules do you see in diabetic nephropathy?
Kimmelsteil-Wilson nodules (gross excess of mesangial matrix forming nodules)
What things will lead to an inevitable decline of a diabetic nephropathy?
Established diabetic nephropathy
Continued poor diabetic control
What can cause crescentic GN?
Wegener’s
Microscopic polyarteritis etc.
Explain how ANCA cause kidney damage in Wegener’s despite not being deposited in the kidney?
These antibodies produce tissue damage via interactions with primed neutrophils and endothelial cells
What drug leads to a 75% remission rate in Wegener’s?
Cyclophosphamide
