Nephrotic Syndrome

Glomerular filtration rate

• Measures the volume of filtrate formed per minute
• Is usually constant – normally is about 90-120 ml/min (is lower in the elderly)
o Autoregulation between 70-150 mmHg keeps it constant
 Myogenic mechanism (increased blood pressure causes arteriole to constrict, and vice versa)
 Macula densa (acts according to [NaCl]
• GFR = NFP (net filtration pressure) x Kf
o NFP = P (gc) – P (bs) – π (gc)
 Gc = glomerular capillary
 Bs = bowman’s space
o Kf = glomerular filtration co-efficient = hydraulic conductivity x glomerular capillary surface area
• GFR falls with:
o Decrease in intrarenal blood flow
o Damage to or loss of glomeruli
o Obstruction to the filtrate through the tubule


Creatinine clearance
• Is used to measure the GFR – once the serum creatinine is elevated, it is a good guide to GFR, and can measure further deterioration
o Serum creatinine does not rise above normal until there is a 50-60% reduction of the GFR
• The level of creatinine in the blood is dependent on age, sex and muscle mass – not affected much by protein intake, unlike urea
• Inulin is the standard
o not used in clinical practise because it is not practical, even though it is only excreted through glomerular filtration
• Creatinine is excreted by both glomerular filtration and tubular secretion
o However, very little is excreted by tubular secretion, so it is basically like inulin
• urine is collected over a period of 24 hours
o plasma level measured within this 24-hour period
o U (urine clearance of creatinine) = V (rate of urine flow) / P (plasma creatinine concentration)


Albumin
• A blood protein – provides the plasma oncotic force
• As the blood passes through the glomerulus, plasma is filtered into Bowman’s space
o Thus, the concentration of albumin rises within the glomerulus
o This draws fluid back into the glomerulus as it exits Bowman’s capsule


Nephrotic syndrome - glomerulopathy
• Hypoalbuminaemia
o Urinary loss of more than 3.5 g daily in adults
o Albumin synthesis rate is increased HOWEVER
 Increased catabolism of reabsorbed albumin in the proximal tubules
 High dietary intake of protein = decreased plasma albumin concentration
• Can be prevented by ACE inhibitors – prevents the increase in urinary albumin excretion due to high protein diet
• Proteinuria
o Partly due to structural damage of the glomerular basement membrane
 Increase in the size and number of pores – passage of more and larger molecules
o Partly due to the reduction of the negative charge components in the glomerular capillary wall
 Proteins not repelled = heavy proteinuria
• Hyperlipidaemia
o Increase in LDLs, VLDLs and intermediate –density lipoproteins (IDLs)
o No change in HDLs
o Is due to increased synthesis of lipoproteins and is also a direct result of low plasma albumin
o Reduced clearance of triglycerides with lipoproteins (VLDLs and chylomicrons) due to albuniuria
• Oedema due to hypoalbuminaemia
o Lower plasma oncotic pressure  less plasma is reabsorbed once is passes across the capillary wall