Session 8: Glomerular Pathology Flashcards
Give examples of where glomerular damage might occur in within the glomerulus.
Subendothelial damage
Glomerular basement membrane damage
Subepithelial damage and damage to podocytes
Mesangial damage and paramesangial damage
Why is it important to know where the damage in the glomerulus has occured?
Because the site of glomerular injury will determine the clinical presenation of the condition.
How can you determine where the damage has occurred in the glomerulus?
By biopsy and then light microscopy to investigate the histology.
Give examples of histological apperances in glomerular conditions.
Focal
Diffuse
Segmental
Global
Membranous
Proliferative
Crescent
Glomerulosclerosis
Glomerulonephritis
Explain focal pathology
Involving less than 50% of the glomerulus on light microscopy
Explain diffuse pathology
Involving more than 50% of glomerulus on LM
Explain segmental pathology
Involving part of the glomerular tuft
Explain global pathology
Involving the entire glomerular tuft
Explain membranous pathology
Thickening of the glomerular capillary wall
Explain proliferative pathology
Increased number of cells in the glomerulus. These can either be glomerular cells or invading inflammatory cells.
Explain crescent pathology
Accumulation of cells in the Bowman’s space
(Associated with more severe disease)
Explain glomerulosclerosis pathology appearance
Segmental or global capillary collapse. No filtration occuring at the sclerotic area
Explain glomerulonephritis pathology appearance
Any condition associated with inflammation of the glomerular tuft
What is nephrotic syndrome?
A triad of symptoms involving damage of the subepithelial region and specifically to the podocytes of the glomerulus. The podocytes are responsible for fine filtration and selectivity of substances across the glomerulus and into the tubular duct.
What is the triad of symptoms in nephrotic syndrome?
Proteinuria of over 350mg/mmol in 24 hours
Hypoalbuminaemia
Oedema
Explain the pathophysiology of nephrotic syndrome.
Podocyte damage leads to less selectivity of the glomerular filtration barrier. This leads to an increase in number of proteins being able to enter the tubular lumen. A large amount of these proteins will be albumin.
This leads to a decreased concentration of albumin in the blood leading to lower capillary oncotic pressure. As the oncotic pressure has decreased the net force between the capillary oncotic pressure, the capillary hydrostatic pressure and the hydrostatic interstitial pressure has now changed.
This leads to the oedema. Commonly the oedema can be found peripheral in hands and feet as well as periorbital oedema.
State of GFR and blood pressure in nephrotic syndrome.
Usually normal
Give another common clinical presenation of nephrotic disease that isn’t included in the triad of symptoms.
Hyperlipidaemia
Explain why hyperlipidaemia might occur in nephrotic syndrome.
As the albumin is low the liver will start to produce more albumin to compensate.
It is thought that this mechanism is accompanied by hepatic synthesis of lipids (cholesterol) as well.
Give common primary causes of nephrotic syndrome.
Minimal Change Glomerulonephritis
Focal Segmental Glomerulosclerosis (FSGS)
Membranous Glomerulonephritis
Give common secondary causes of nephrotic syndrome.
Diabetes Mellitus (T1 &T2)
Renal amyloidosis
Connective tissue disorders such as Systematic Erythematous Lupus (SLE)
Age group of Minimal Change Glomerulonephritis.
Childhood/Adolescence with a reduced incidence in increasing ages
Treatment of MCG
Usually responds to steroids
Progression to renal failure in MCG?
Not common
Histological appearance of MCG.
Minimal and sometimes negligible changes hence its name Minimal Change Glomerulonephritis
However on electron transmission microscopy you might find that there is absence of podocytes
Pathogenesis of MCG.
Unknown but thought to be a circulating factor damaging the podocytes.
This is because it seems to be something wrong with the blood as blood transfusions has caused MCG
Age group of Focal Segmental Glomerulosclerosis (FSGS)
Adults
Difference between MCG and FSGS
FSGS is not normally found in children and adolescence, more commonly found in adults.
FSGS is less responsive to steroids.
FSGS expresses glomerulosclerosis.
FSGS more commonly progresses to renal failure.
Pathogenesis of FSGS.
Unknown as well. Thought to be a circulating factor damaging podocytes.
Which is the most common primary cause of nephrotic syndrome in adults?
Membranous glomerulonephritis
What is special in Membranous glomerulonephritis compared to MCG and FSGS?
That is is due to immune complex deposits and thus probably autoimmune.
What might membranous glomerulonephritis be secondary to?
Other pathologies like lymphoma
What is nephritic syndrome?
Not to be confused with nephrotic syndrome. It is an inflammation of the glomerulus expressing a triad of symptoms.
What is the triad of symptoms in nephritic syndrome?
Haematuria
Hypertension
Reduced GFR
Explain the pathophysiology in nephritic syndrome.
There is inflammation of the glomerular capillaries. This leads to leaky capillaries as the consequence of the inflammatory process.
This means that erythrocytes (haematuria) and leukocytes (pyuria) can escape and enter the tubular lumen.
There are however still podocytes so the selectivity has not decreased so the proteinuria is rather mild.
The inflammation also damage the glomerulus as a whole and will lead to reduced GFR as well as oliguria with azotemia.
Give causes of nephritic syndrome.
IgA nephropathy also called Berger’s disease
Anti-GBM disease also called Goodpasture syndrome
ANCA - Vasculitis
Alport Syndrome
Thin glomerular basement membrane disease
SLE
Acute proliferative glomerulonephritis
Rapidly progressive glomerulonephritis
Most common cause of nephrotic syndrome.
IgA Nephropathy
Age group of IgA nephropathy.
Any age.
Classical presentation of IgA nephropathy.
Visible or invisible haematuria.
Mucosal infections (hence IgA)
+/- proteinuria
Significant proportion progressing to renal failure.
Treatment of IgA nephropathy.
No effective treatment
Histological appearance of IgA nephropathy.
Usually mesangial damageas the IgA can reach the mesangium and deposit to damage it.
Pathogenesis of IgA nephropathy.
Deposition of circulating IgA containing immune complexes in the glomerulus.
Give examples of hereditary nephropathies.
Thin GBM nephropathy
Beningn familial nephropathy
Isolated haematuria
Thin GBM
Alport Syndrome
What is Alport syndrome?
X-linked recessive disease where there is abnormal collagen IV found. This causes abnormal appearance of the GBM where it is split and laminated.
Classical presentation of Alport Syndrome.
Ear problems (deafness)
Eye problems
Kidneys problems progressing to renal failure
Explain what Anti-GBM aka Goodpasture syndrome is.
A relatively uncommon but important syndrome. This is because it is a rapidly progressive glomerulonephritis that can cause acute onset of severe nephritic syndrome and end stage renal failure.
What clinical presentation is anti-GBM commonly associated with?
Pulmonary haemorrhage.
What causes anti-GBM?
Autoantibody to collagen IV in the basement membrane of the glomerulus.
Treatment of anti-GBM.
Treatable by immunosuppression and plasmaphoresis.
This is however only possible if the condition has been caught early.
What is vasculitis?
A group of systemic disorders where there is no immune complex or antibody deposition.
It is however associated with Anti Neutrophil Cytoplasmic Antibody and also called ANCA-Vasculitis.
It can cause nephritic syndrome.
Treatment of ANCA-vasculitis.
Glucocorticoids like prednisolone.
It is treatable if caught early.
Histological presentation of ANCA-vasculitis.
Segmental necrosis and crescent.
