GLOMERULAR FILTRATION RATE (GFR) & FACTORS AFFECTING
GLOMERULAR FILTRATION RATE (GFR)
GLOMERULAR FILTRATE:
- Fluid filtered out from blood into uriniferous tubule is glomerular filtrate.
- Process of glomerular filtration is first step in formation of urine.
- Filteration occurs in glomerular capillaries.
FILTRATION SURFACE/BARRIER:
- Glomerular membrane
Is three-layered structure –
- Glomerular capillary endothelium
- Basement membrane (Basal lamina)/ “Functional barrier”
- Visceral epithelium of Bowman’s capsule along with their foot process
Functional barrier:
- Is Basement membrane.
- Performs selectivity & filtration function of glomerular membrane.
Filteration is by,
- Hydrated channels approx. 6 nm wide.
Factors influencing:
1. Membrane charge:
- Membrane glycoproteins are strongly negatively charged.
- Hence, filtration surface is impermeable to negatively substances(e.g., plasma proteins, albumin).
– No protein content in filtarte.
Clinical implication:
- Loss of negative charge on basement membrane without structural membrane damage is enough to produce albuminuria.
- Hence, albuminuria is such a sensitive indicator of glomerular disease
2. Size of channels & Molecular size of substance:
- About 6 nm
– Passage of neutral/positively charged molecules is difficult.
- Molecules < 4 nm diameter – Freely filtered
- Molecules > 8 nm diameter – Unfiltered
- Molecules bt. 4-8 nm diameter – Difficult filtration (proportionately increasing with size).
Metrics:
- In man, resting glomerular filtration rate is about 125 ml/min
- About one-fifth (20%) of plasma passing through kidney is filtered.
- Filtration fraction – 0.2 (Fraction of renal plasma flow filtered)
DETERMINANTS OF GFR:
GFR determined by
- Net filtration pressure
– Hydrostatic pressure
– Colloid osmotic pressure
- Glomerular capillary filtration coefficient (Kf)
1. Net effective filtration pressure:
- Sum of hydrostatic & colloid osmotic forces across glomerular membrane
- Forces either favor or oppose filtration
- Net effective pressure
– Forces promoting filtration – Forces opposing filtration
– I.e., (PG + ∏B) – (PB + ∏G)
– Net effective filtration pressure – 10 mm/Hg
Factors promoting filtration:
- Calculated by, (PG + ∏B)
- Hydrostatic pressure in glomerular capillaries (PG) – 60mm Hg.
– Most important determinant of GFR
- Nil/Zero Bowman’s capsule colloid osmotic pressure (∏B)
Factors opposing filtration:
- Calculated by, (PB + ∏G)
- Hydrostatic pressure in Bowman’s capsule (PB) – 18mm Hg
- Glomerular capillary colloid osmotic/oncotic pressure (∏G) – 32 mm Hg
Net value:
- I.e., (PG + ∏B) – (PB + ∏G)
- (60 + 0) – (18+32) = 60 – 50
- Net effective filtration pressure – 10 mm/Hg
2. Glomerular capillary filtration coefficient (Kf):
- Kf = 12.5 ml
- Glomeruli of both kidneys allow 12.5 ml of filtrate formation every minute for every mm/Hg pressure gradient.
Formula for GRF:
- Mathematically, GFR equals product of Kf & net filtration pressure
- GFR = Kf * net filtration pressure
- Normal resting glomerular filtration rate – Approx. 125 ml/min
EFFECTS ON GRF:
1. Effect of Hydrostatic pressure on GRF:
- Increased glomerular capillary hydrostatic pressure→ Increases GFR
Glomerular hydrostatic pressure is determined by,
- Arterial pressure, Afferent & Efferent arteriolar resistance
- In turn, each parameter affects GFR.
1 a) Arterial pressure on GFR:
- ↑ed arterial pressure /Hypertension → ↑es glomerular hydrostatic pressure → ↑es GFR
- ↓ed arterial pressure/Hypotension → ↓es GFR
1 b) Afferent arteriolar resistance on GFR:
- ↑edafferent arteriole resistance(constriction) → ↓es glomerular hydrostatic pressure → ↓es GFR
- ↓ed afferent arteriole resistance(dilation) → ↑es glomerular hydrostatic pressure → ↑es GFR
1 c) Efferent arteriolar resistance on GFR:
- Increased efferent arteriole resistance (Constriction) has biphasic effect on GFR
Moderate constriction → slight ↑es GFR
– Severe constriction → ↓es GFR
- ↓edefferent arteriole resistance(dilation)→↓es glomerular hydrostatic pressure →↓es GFR
2. Effect of glomerular capillary colloid osmotic/oncotic pressure on GFR:
- ↑ed colloid osmotic pressure → ↓es GFR
- ↓ed colloid osmotic pressure → ↑es GFR
– Eg., Hypoproteinemia
3. Effect of renal blood flow on GFR:
- ↑ed renal blood flow → ↑es GFR
- ↓ed renal blood flow → ↓es GFR
4. Effect of mesangial cells & Kf on GFR:
- ↓ed Glomerular capillary filtration coefficient (Kf)→ ↓es GFR
- Kf altered by mesangial cells
- Contraction of mesangial cells → ↓es Kf & GFR.
- Caused by endothelin, angiotensin II, vasopressin, PGF2 & Histamine.
- Relaxation of mesangial cells → ↑es Kf & GFR
- Caused by ANP, Dopamine, PGE2 & cAMP
5. Other factor effecting GFR:
- ↑ed Bowman’s capsule hydrostatic pressure → ↑ed tubular hydrostatic pressure (result of obstruction) → ↓es GFR
Exam Important
GLOMERULAR FILTRATION RATE (GFR)
Filtration barrier/surface:
- Glomerular membrane.
- Basement membrane acts as “Functional barrier”
- Performs selectivity & filtration function of glomerular membrane.
- Filtration done by, hydrated channels approx. 6 nm wide
Factors influencing:
Membrane charge:
- Membrane glycoproteins are strongly negatively charged.
- Hence, filtration surface is impermeable to negatively substances.
- e.g., like plasma proteins, albumin.
Clinical implication:
- Albuminuria is such a sensitive indicator of glomerular disease
- Size of filtration channels:
– About 7 nm
Metrics:
- Resting glomerular filtration rate is about 125 ml/min
- About one-fifth (20%) of plasma passing through kidney is filtered.
- Filtration fraction – 0.2
DETERMINANTS OF GFR:
1. Net effective filtration pressure:
- 10 mm/Hg
Factors promoting filtration:
- Hydrostatic pressure in glomerular capillaries – 60mm Hg.
– Most important determinant of GFR
- Nil/Zero Bowman’s capsule colloid osmotic pressure
Factors opposing filtration:
- Hydrostatic pressure in Bowman’s capsule (PB) – 18mm Hg
- Glomerular capillary colloid osmotic/oncotic pressure (∏G) – 32 mm Hg
Formula for GRF:
- GFR = Kf * net filtration pressure
- Normal resting glomerular filtration rate – Approx. 125 ml/min
EFFECTS ON GRF:
1. Effect of Hydrostatic pressure on GRF:
- Increased glomerular capillary hydrostatic pressure → Increases GFR
- Glomerular hydrostatic pressure inturn determined by,
– Arterial pressure, Afferent & Efferent arteriolar resistance
1 a) Arterial pressure on GFR:
- ↓ed arterial pressure/Hypotension → ↓ed GFR
1 b) Afferent arteriolar resistance on GFR:
- ↑ed afferent arteriole resistance(constriction)→ ↓ed GFR
- ↓ed afferent arteriole resistance(dilation)→ ↑es GFR
1 c) Efferent arteriolar resistance on GFR:
- Increased efferent arteriole resistance (Constriction) has biphasic effect on GFR
- Moderate constriction → slight ↑es GFR.
- ↓ed efferent arteriole resistance(dilation)→ ↓es GFR.
2. Effect of glomerular capillary colloid osmotic/oncotic pressure on GFR:
- ↑ed colloid osmotic pressure →↓es GFR.
- ↓ed colloid osmotic pressure → ↑es GFR.
– Eg: Hypoproteinemia.
3. Effect of renal blood flow on GFR:
- ↑ed renal blood flow → ↑es GFR
4. Effect of mesangial cells & Kf on GFR:
- ↓ed Glomerular capillary filtration coefficient (Kf) → ↓es GFR
- Kf altered by mesangial cells
- Contraction of mesangial cells → ↓es Kf & GFR
– Caused by endothelin, angiotensin II, vasopressin, PGF2 & Histamine.
- Relaxation of mesangial cells → ↑es Kf & GFR
– Caused by ANP, Dopamine, PGE2 & cAMP
5. Other factor affecting GFR:
- ↑ed Bowman’s capsule hydrostatic pressure →↑ed tubular hydrostatic pressure (result of obstruction) → inturn results in →> ↓es GFR
Don’t Forget to Solve all the previous Year Question asked on GLOMERULAR FILTRATION RATE (GFR) & FACTORS AFFECTING
Click Here to Start Quiz
Click Here to Start Quiz
