GLOMERULAR DISEASE Flashcards
What are the two main defining findings of glomerular disease?
Proteinuria
Haematuria
What part of the glomerulus is damaged if there is haematuria (and small amounts of proteinuria)?
Capillary endothelial cell lining
Endothelial side of the glomerular basement membrane
What part of the glomerulus is damaged if there is proteinuria (but not haematuria)?
Podocytes
Podocyte side of the glomerular basement membrane
When thinking about glomerular disease what are the three different elements to consider?
Syndrome - presenting condition
Histological pattern - biopsy picture
Disease cause
What are the three presenting syndromes associated with glomerular disease?
Nephrotic syndrome
Nephritic syndrome
Mixed nephritic/nephrotic picture
(Asymptomatic proteinuria/haematuria)
What do we mean by asymptomatc proteinuria/haematuria?
Where there are no other features of the protein or blood loss such as those seen in nephrotic or nephritis syndromes.
What are the main features of nephrotic syndrome?
Protein loss of more than 3.5g per day. This leads to the clinical picture:
Hypoalbuminaemia (serum albumin typically less than 25g/L)
Oedema
Hyperlipidaemia/Hypercholesteraemia
(Hypercoagulability - not alway considered a mainstay of nephrotic syndrome)
Why do people with nephrotic syndrome get oedema?
Hypoalbuminaemia leads to a loss of oncotic pressure which means water is pulled out into the tissues.
The resulting hypovolaemia leads to stimulation of the renin-angiotensin system which leads to retention of more water.
Why do people with nephrotic syndrome develop hyperlipidaemia?
The lack of protein the blood stimulates the liver to produce more protein, resulting in the overproduction of lipoproteins.
There is also a loss of lipoprotein lipase from the kidneys so lipid breakdown is reduced.
Why do people with nephrotic syndrome develop hypercoagulability?
This is mainly due to a relatively big loss of antithrombin III.
What are the other less common features of nephrotic syndrome, other than protein loss, hypoalbuminaemia, hyperlipidaemia, oedema and hypercoagulability?
Hypertension - can also be a cause
Anaemia due to loss of transferrin
Dyspnea - due to pulmonary oedema
Lipiduria - fat globules can also make their way through the glomerulus
How we treat all patients currently suffering nephrotic syndrome regardless of the cause or histological pattern?
Blood pressure control
ACE inhibitors reduce proteinuria
Control hyperlipidaemia
Anticoagulate as increased risk of thrombosis with loss of clotting factors
Treat underlying cause
What are the three main structures of the glomerulus that can be damaged to cause disease?
Capillary endothelial cell lining
(Mesangium supporting the capillaries)
Glomerular basement membrane
Podocytes on the outer surface of the glomerulus
What are the histological patterns associated with nephrotic syndrome?
Minimal change nephropathy
Membranous glomerulonephritis
Focal segmental glomerulosclerosis
What is the histological pattern of minimal change disease?
Damage to the podocytes only seen on electron microscopy
What is the histological pattern of membranous glomerulonephropathy?
Widespread glomerular basement thickening
Subepithelial deposition of immune complexes
What is the histological pattern of focal segmental glomerulosclerosis?
Podocyte foot process fusion or fibrosis, with hyaline deposits in the glomerular segments.
What are the causes of nephrotic syndrome with a minimal change nephropathy histological pattern?
Idiopathic minimal change disease
Possibly NSAID related
Diabetes can produce the same picture
Who tends to be affected by idiopathic minimal change disease of the glomerulus?
Most common (90%) cause of nephrotic syndrome in children often following an upper respiratory tract infection.
What are the non-renal disorders associated with idiopathic minimal change disease of the glomerulus?
Asthma
Eczema
Hay fever
How is idiopathic minimal change disease of the glomerulus treated?
Corticosteroids and ciclosporin
What are the causes of nephrotic syndrome with a membranous glomerulonephritis histological pattern?
Idiopathic membranous glomerulonephropathy
Infections: syphilis, malaria, hepatitis B
Tumours: melanoma, carcinoma of the bronchus, lymphoma
Drugs: penicillamine, heroin, mercury, gold
What are the infections which can cause nephrotic syndrome with a membranous glomerulonephritis histological pattern?
Syphilis
Malaria
Hepatitis B
What are the tumours which can cause nephrotic syndrome with a membranous glomerulonephritis histological pattern?
Melanoma
Carcinoma of the bronchus
Lymphoma
What are the drugs which can cause nephrotic syndrome with a membranous nephropathy histological pattern?
Penicillamine
Heroin
Mercury
Gold
How is nephrotic syndrome with a membranous glomerulonephritisc histological pattern treated?
Corticosteroids
Ciclosporin
Cyclophosphamide
Chlorambucil
Treat underlying cause if secondary
1/3 resolve, 1/3 respond to cytotoxics, 1/3 develop chronic kidney disease
What are the causes of nephrotic syndrome with a focal segmental glomerulosclerotic histological pattern?
Idiopathic focal segmental glomerulosclerosis
AIDS
Heroin use
Amyloidosis
How is nephrotic syndrome with a focal segmental glomerulosclerotic histological pattern treated?
Steroids, cyclophosphamide, ciclosporin, dialysis and renal transplant.
Recurrence does happen in transplanted patients.
What proportion of cases of nephrotic syndrome does the focal segmental glomerulosclerotic pattern account for?
Up to 15-30% of adults
10% of children
Does a focal segmental glomerulosclerotic histological pattern always present with the features of nephrotic syndrome?
No. It can progress to haematuria as well.