Glomerular Filtration Rate

Glomerular Filtration

Glomerular Filtration Rate (GFR) is the amount of plasma filtered from Glomerular membrane into bowmen space.

Glomerular filtration rate can be discuss under following heading

• Glomerular Filtration Rate  Composition
• Glomerular Filtration Rate  Amount
• Glomerular Filtration Rate  Determinants
• Forces affecting Glomerular Filtration Rate
• Factors affecting Glomerular Filtration Rate
• Measurement of Glomerular Filtration Rate
  • Inulin clearance test
  • Creatinine clearance test
  • Urea clearance test
  • Radioactive iothalamate

Composition of Glomerular filtrate

• Its composition is same as plasma except plasma proteins and blood cells.
• Small molecular weight substance (Fatty acid and Ca2+) are bound to plasma proteins so are not filtered.
• Plasma proteins are not filtered because.
  • Size of pores /permeability is < 8 nm.
  • Negative charge glycoproteins are presents on podocyte which repels protein.

Glomerular Filtration Rate  Amount

• Normal = 125ml/min or 180liters/day.
• Filtration fraction = (GFR/RPF) = 0.2
• GFR = 20% of renal plasma flow (RPF).

N.B. Filtration Fraction is ratio of Glomerular filtration rate to renal flow

Glomerular Filtration Rate  Determinants

GFR is determined by

• Glomerular capillary filtration coefficient (Kf).
• Starling forces across Glomerular capsule and bowmen space.
  GFR = KfX net filtration Pressure

Glomerular capillary filtration coefficient (Kf) – It is product of glomerular membrane hydraulic permeability (conductivity) and effective filtration surface area. It cannot be measured directly but can be derived indirectly as follows.
GFR = KfX net filtration Pressure

Kf = GFR/Net filtration pressure = 125/10 = 12.5m2/min/mmHg

Net-filtration pressure represents sum of hydrostatic and colloid osmotic pressure.

GFR = kfX net filtration pressure : kfX (Pg – Pb – JIg+ JIb)

GFR = 12.5 X (60 -18 – 32 + 0): 12.5 X 10: 125ml/min

Factors affecting GFR / Regulation of GFR

• Forces affecting GFR
  • Pg = Glomerular capillary hydrostatic pressure
    It is primary mean for physiological regulation of GFR. GFR is directly proportional to Pg. Pg depends on three factors.
    • Arterial pressure – GFR is auto regulated between arterial pressure range 80-200 mmhg. If arterial pressure >200 mmhg then GFR increases. If arterial pressure <80 mmhg then GFR decreases.
    • Afferent arteriolar resistance (AAR) – it is increases by sympathetic activity or hormones like epinephrine and norepinephrine. Increased afferent arteriolar resistance will decrease blood flow and so will decrease Glomerular capillary hydrostatic pressure which in turn will reduce GFR.
      ↑ AAR →↓ BF →↓ Pg →↓ GFR
    • Efferent arteriolar resistance – it is increases by Angiotensin 2. There are 2 different effects.
• Moderate increase in efferent arteriolar resistance – it will decrease renal blood flow that will increase hydrostatic pressure and will increase GFR. Increased GFR will increase filtration. Due to increased plasma filtration the concentration of plasma proteins increases. (↑JIg)

Severe increase in efferent arteriolar resistance – It will decrease renal blood flow that will decrease hydrostatic pressures. Due to decrease in blood flow GFR will decrease. It is in contrast to above phenomenon. In this case as there is no output the blood flow stops which decreases GFR. Filtration fraction will also decrease . Nonlinear increase in colloid osmotic pressure of glomerulus occurs due to donnans effect. (Interaction of ions bound to plasma protein).

Bowman’s capsule hydrostatic pressure (Pb)

It does not serve as primary mean of GFR regulation but play role in pathological conditions like urinary tract obstruction (stones). During obstruction to urinary flow, Bowman’s capsule hydrostatic pressure increases. It then decreases GFR and can lead to renal failure if not treated.

Glomerular colloid osmotic pressure (JIg)

It is a force that opposes Glomerular filtration. Normally 20o/o plasma that passes through kidney gets is filtered at glomerulus. Therefore concentration of plasma protein in blood of Glomerular capillary gets concentrated by 20%. Glomerular colloid osmotic pressure is affected by two factors.

Glomerular capillary filtration coefficient (Kf):-

• Glomerular membrane hydraulic permeability (conductivity) is directly proportional to GFR.
• Effective filtration surface area is directly proportional to GFR.
• Contraction of Glomerular mesangial cells:- decreases GFR by decreasing surface area.

Renal blood flow

• It is directly proportional to GFR.

Sympathetic stimulation

• Strong sympathetic stimulation will decrease renal blood flow and will decrease GFR.

Tubuloglomerular feedback

It is a feedback mechanism which controls constant blood flow, by sensing sodium chloride concentration at macula densa and accordingly changes the afferent and efferent arteriolar diameter. It ensures constant delivery of sodium chloride at distal convoluted tubule. It has two components.

• Afferent arteriole loop
• Efferent arteriole loop

Hormones and local factors:-

Diet:-

Measurement of GFR

GFR can be measured by

• Insulin clearance test.
• Creatinine clearance test.
• Urea clearance test.
• Radioactive iothalamate.

Properties of substance that can be used to measure GFR:-

• Its arterial and venous concentration should be measurable
• It should not be metabolized.
• Itshould not be Stored.
• It should not be synthesized by the kidney.
• It should not affect renal blood flow.
• It should be completely filtered.
• It should not be reabsorbed.
• It should not be secreted.

Insulin clearance test:-

• Insulin is a dye, fructopolysachharide extracted from the roots of plants.
• It does not exist naturally in the body.
• It is biologically inert/non-toxic.
• It is neither stored nor metabolized in the body.
• Its concentration can be easily measured.
• It is freely filtered, neither reabsorbed nor secreted.

Creatinine clearance test:-

• Creatinine is a byproduct of muscle metabolism, so not a perfect marker.
• It is freely filtered, and a small amount is secreted, so less accurate than an insulin clearance test.
• A slight error in measuring plasma creatinine leads to an overestimated plasma creatinine value.
• The above two effects cancel each other.
• As it does not require intravenous infusion it is widely used.
• Plasma creatinine concentration is 0.6-l.5 mg/dl.
• Creatinine clearance is 80-110 mg/min.

Urea clearance test:-

• It is the end product of protein metabolism.
• It is freely filtered, and a small amount is reabsorbed (Clearance < GFR) so less sensitive.

Glomerular Filtration Rate Method

At the beginning of the test, the patient is asked to empty the bladder. After 1 hour, collect 1 hr. urine sample. Measure urinary urea levels and serum urea level.

If urinary output > 2ml/min, maximal urea clearance test is used Curea = Urea X V/Purea.

If urinary output < 2ml/min, a standard urea clearance test is used Curea = Urea X√V/Purea.

Normal values of Curea by maximal urea clearance test: 75ml/min.

Normal values of Curea by standard urea clearance test: 54 ml/min.