Pathology Flashcards
Where are the four sites for glomerular injury?
Subepithelial affects podocytes/podocyte side of basement membrane
Within glomerular basement membrane
Sub endothelial - inside basement membrane
Mesangial/paramesagial - supporting the capillary loop
What problems can occur with the glomerular filter and signs of this?
Get blocked -> renal failure
- hypertensive
- haematuria
Can leak
- proteinuria (albumin)
- haematuria
Can both occur together
What is proteinuria
Presence of excess serum proteins in urine
What allows proteins to leak through the filtration barrier?
Podocyte damage
- widening of fenestration slits
- causes proteins to be leaked when they would normally not be filtered
Causes of nephrotic syndrome/proteinuria?
Minimal change glomerulonephritis
Minimal change focal glomerulosclerosis
Membranous glomerulonephritis
When is minimal change glomerulonephritis seen?
Childhood/adolescence
Decreasing incidence with age
What happens in minimal change glomerulonephritis?
Podocyte damage mediated by T cells
Under light microscope, appears normal, under electron microscope, can see podocyte damage
How is minimal change glomerulonephritis treated?
Steroids
Relapse common if stopped
What does each part of the name focal segmental glomerulosclerosis mean?
Focal - involves
What happens in focal segmental glomerulosclerosis?
Podocytes undergo damage and subsequent scarring
-> protein in urine
Caused by a circulating factor (because transplanted kidneys undergo the same damage)
What is the commonest cause of nephrotic syndrome in adults?
Membranous glomerulonephritis
What can focal segmental glomerulosclerosis lead to?
Renal failure
What happens in membranous glomerulonephritis?
Immune complex deposits in sub-epithelial space
Autoimmune basis caused by an auto-antibody to podocytes
Evidence that it may be secondary because it is associated with other conditions such as lymphoma
Prognosis of membranous glomerulonephritis?
Rule of thirds
- third will remit
- third will continue in nephrotic state
- third will show progressive loss of renal function
What is nephritic syndrome?
Renal failure due to blocking of the filter
What can cause nephritic syndrome?
IgA nephropathy
Hereditary nephropathies
- Thin GBM nephropathy
- Alport
Diabetes mellitus
Goodpasture’s syndrome
Vasculitis
What is the most common glomerular nephropathy?
IgA nephropathy
Can happen at any age
What happens in IgA nephropathy?
Deposition of IgA antibodies in the glomerulus
Can lead to mesangial proliferation and scarring
Presentation of IgA nephropathy?
Visible/invisible haematuria
Some patients have proteinuria
Relationship with mucosal infections
Significant number progress to renal failure
Treatment of IgA nephropathy?
None
What is thin glomerular basement membrane nephropathy? Features?
A benign familial nephropathy
Isolated haematuria
Thin GBM
Benign course
What is Alport?
X linked causing abnormal collagen IV production
Get abnormal appearance of GBM a
Can progress to renal failure
What is Alport associated with?
Deafness
How can diabetes mellitus lead to nephritic syndrome?
Microvasculature is damaged which damages the glomerulus
Get expansion of mesangium with collagen deposition - mesangium sclerosis
Thickening of the basement membrane (4.5x of normal)
What causes diabetes mellitus to lead to nephritic syndrome?
infections
abnormality of blood supply from atheroma or microvascular disease
What is seen in nephritic syndrome caused by diabetes?
Progressive proteinuria
Progressive renal failure
What is Goodpasture’s syndrome characterised by?
Acute onset of severe nephritic symptoms
Combination of glomerulonephritis with pulmonary (alveolar) haemorrhage -> haemoptysis
Deposition of IgG
Pathology of Goodpasture’s syndrome?
Circulating anti-glomerular basement membrane antibodies bind to basement membranes (collagen IV) in lungs and kidney, fix complement and trigger a cell-mediated inflammatory response
This causes glomerulonephritis and pulmonary capillaries
Pre-disposing factors of Goodpasture’s syndrome?
HLA-DR2 gene Smoking Influenza Exposure to organic solvents or hydrocarbons Codeine inhalation Metal dusts
How do you treat Goodpasture’s syndrome?
Immunosuppression
Plasmaphoresis if caught early
What is vasculitis?
Inflammation of blood vessels
How does vasculitis lead to nephritic syndrome?
Blood vessels in the glomerulus see attack end and become inflamed by neutrophil cytoplasmic antibody (ANCA)
What is the mechanism for getting sub-epithelial deposits?
Antigen on podocytes abnormally recognised
Circulating IgG binds to it, forming immune complexes in the glomerulus
Eg membranous glomerulonephritis
What is the mesangium?
Cells continuous with the smooth muscle of the arteriolar wall in the afferent arteriole in the glomerulus. Not blocked by podocytes.
Mechanism for mesangial deposits?
Immune complexes are deposited directly into the mesangium as there are no podocytes or basement membrane to act as a barrier
