Principles and practice of Human Pathology – Lecture 18 + 19 (22-6-2018):
Research on Nephropathology (Experimental nephropathology)
Glomerular filtration barrier:
- Nephrotic syndrome: heavy proteinuria, hypoalbuminemia, hyperlipidemia and
edema
o Cause: a leaky filter
Pre-urine contains about 10kg of protein
Only 1g of the protein passes the glomerular filtration barrier of the kidney filter is
really selective.
The classical model of glomerular permselectivity:
The filter:
Glomerular filtration barrier is size and charge selective negatively charged
molecules cannot pass.
Why does the filter never clog?
Hypothesis: Due to filtration of charged molecules there is an electric potential over
the filtration barrier. Any molecule in the barrier will be removed by electrophoresis
Problem: how to measure an electric current in something so small as the glomerular
complex?
Mudpuppy:
Mudpuppy have similar glomeruli to human, but much larger.
Electrical forces determine glomerular permeability:
Positively charged into the urine.
Negatively charged into the blood.
Proteinuria and podocyte foot process effacement:
Proteinuria: loss of filtration leads to an increased permeability (loss of the electric
potential).
Loss of the electrophoresis force filter becomes leaky.
The electrokinetic model:
This concept turns the glomerular filter from a passive into an active and dynamic
filter, with a self-cleating mechanism and variable size and charge selectivity.
Focal segmental glomerulosclerosis (FSGS):
Sclerosis = scarring.
Focal: not all glomeruli are affected
Segmental: only a part of the glomerulus is affected.
Development of FSGS lesions:
- The role of parietal epithelial cells (PECs).
Research on Nephropathology (Experimental nephropathology)
Glomerular filtration barrier:
- Nephrotic syndrome: heavy proteinuria, hypoalbuminemia, hyperlipidemia and
edema
o Cause: a leaky filter
Pre-urine contains about 10kg of protein
Only 1g of the protein passes the glomerular filtration barrier of the kidney filter is
really selective.
The classical model of glomerular permselectivity:
The filter:
Glomerular filtration barrier is size and charge selective negatively charged
molecules cannot pass.
Why does the filter never clog?
Hypothesis: Due to filtration of charged molecules there is an electric potential over
the filtration barrier. Any molecule in the barrier will be removed by electrophoresis
Problem: how to measure an electric current in something so small as the glomerular
complex?
Mudpuppy:
Mudpuppy have similar glomeruli to human, but much larger.
Electrical forces determine glomerular permeability:
Positively charged into the urine.
Negatively charged into the blood.
Proteinuria and podocyte foot process effacement:
Proteinuria: loss of filtration leads to an increased permeability (loss of the electric
potential).
Loss of the electrophoresis force filter becomes leaky.
The electrokinetic model:
This concept turns the glomerular filter from a passive into an active and dynamic
filter, with a self-cleating mechanism and variable size and charge selectivity.
Focal segmental glomerulosclerosis (FSGS):
Sclerosis = scarring.
Focal: not all glomeruli are affected
Segmental: only a part of the glomerulus is affected.
Development of FSGS lesions:
- The role of parietal epithelial cells (PECs).
