Nephrotic syndrome
Filtration membrane made of
- endothelial cells
- glomerular basement membrane - visceral epithelial cells podocytes
Glomerular diseases alter the characteristics of this filtration membrane
Endothelial cells are fenestrated, they contain pores. Fenestration size 70 to 100 nanometers
Podocytes interdigitate with each other.
- their foot processes are applied on the GBM =» if they detach the membrane becomes more
permeable
- the gaps between interdigitation are called filtration slits, their size is 20-30 nm
To filtrate into urine, molecules must pass through
1- size barrier (fenestrations, filtration slits)
2- negative charge barrier
On the filtration membrane, there are negative charges at multiple levels (endoth c, GBM, ),
they repel negatively charged molecules.
Plasma proteins at normal pH are negatively charged, they will be repelled by the negative
charges.
Albumin 70 KDa
Albumin size is just enough to let it pass through the size barrier
But normally albumin does not pass because it is negatively charged so it is repelled by the
charge barrier.
In minimal change disease there is not structural modifications but negative charges are lost
albumin starts leaking out.
Let's go through what happens in different degrees of injury.
Grade 1 mild injury +
Small molecules start leaking first.
Albuminuria or selective proteinuria
Which means that the damage allows albumin to pass but not globulin
Injury ++
The membrane is more leaky there will be non-selective proteinuria < 3,5 g/day
Injury +++
Non selective proteinuria in higher amounts
> 3,5 g / day in urine
Once proteinuria become >3,5g/d
There will be a change in the clinical picture and further complications will develop, From this
point, the compensatory potential of liver is depassé and it can't maintain normal plasma protein
levels.
Healthy liver produce 10-12 g plasma protein per day
Mistery :/
Production 12 g/d
loss 3,5 g/d
in serum hypoproteinemia
The real loss is not only 3,5 g/d
Filtration membrane made of
- endothelial cells
- glomerular basement membrane - visceral epithelial cells podocytes
Glomerular diseases alter the characteristics of this filtration membrane
Endothelial cells are fenestrated, they contain pores. Fenestration size 70 to 100 nanometers
Podocytes interdigitate with each other.
- their foot processes are applied on the GBM =» if they detach the membrane becomes more
permeable
- the gaps between interdigitation are called filtration slits, their size is 20-30 nm
To filtrate into urine, molecules must pass through
1- size barrier (fenestrations, filtration slits)
2- negative charge barrier
On the filtration membrane, there are negative charges at multiple levels (endoth c, GBM, ),
they repel negatively charged molecules.
Plasma proteins at normal pH are negatively charged, they will be repelled by the negative
charges.
Albumin 70 KDa
Albumin size is just enough to let it pass through the size barrier
But normally albumin does not pass because it is negatively charged so it is repelled by the
charge barrier.
In minimal change disease there is not structural modifications but negative charges are lost
albumin starts leaking out.
Let's go through what happens in different degrees of injury.
Grade 1 mild injury +
Small molecules start leaking first.
Albuminuria or selective proteinuria
Which means that the damage allows albumin to pass but not globulin
Injury ++
The membrane is more leaky there will be non-selective proteinuria < 3,5 g/day
Injury +++
Non selective proteinuria in higher amounts
> 3,5 g / day in urine
Once proteinuria become >3,5g/d
There will be a change in the clinical picture and further complications will develop, From this
point, the compensatory potential of liver is depassé and it can't maintain normal plasma protein
levels.
Healthy liver produce 10-12 g plasma protein per day
Mistery :/
Production 12 g/d
loss 3,5 g/d
in serum hypoproteinemia
The real loss is not only 3,5 g/d
