Glomerular filtration rate (GFR):

**Glomerular filtration rate (GFR):
It is the fluid that filtrates through the glomerular into Bowman’s capsule each minute. It is about 125 ml/ min. or 180 L / day in males (10% lower in female). Also called creatinine clearance (Ccr ) and calculated as following:
Ccr = [(140-age in years)X (body weight in kg)]/Pcr
[multiply result x 1.22 for male patients or 1.04 for female]. Where Pcr = plasma creatinine.
The high GFR is due to very high permeability of the capillaries of glomerulus. Because the inner side of the pores of glomerular membrane is negatively charged repelling other negatively charged molecules that tend to pass through pores. So the glomerular membrane is completely impermeable to all plasma proteins (-ve charge) but is highly permeable to all other dissolved substances in normal plasma. So the composition of the glomerular filtrate is the same as plasma except that it has no significant amount of proteins.
Forces that regulate GFR:
a) Forces favoring filtration (mmHg):
1. Glomerular hydrostatic pressure =60 mmHg.
2. Bowman’s capsule colloid osmotic pressure = 0 mmHg.
b) Forces opposing filtration (mmHg):
1. Bowman’s capsule hydrostatic pressure =18 mmHg.
2. Glomerular capillary colloid osmotic pressure =32 mmHg.
Net filtration pressure = 60- 18 - 32 = 10 mm Hg.
**Physiological control of renal blood flow (RBF) and GFR
The factors that affect the RBF and GFR are:
1. Neural factor
2. Hormonal factor
3. Autoregulation
1. Neural factor:
Sympathetic nervous system
All the blood vessels of kidneys are richly innervated by sympathetic nerve fibers. Strong activation of renal sympathetic nervous can constrict the renal arterioles and decrease BF and GFR.
NOTE: Renal sympathetic nerves stimulation are important in reducing renal BF and GFR during sever acute disturbances such as sever hemorrhage or brain ischemia this will lead to decrease the GFR and decrease the urine out- put and keep the blood volume within normal .
2. Hormonal factors:
• Norepinephrine, Epinephrine, and Endothelin: constrict blood vessels and decrease GFR. Blood level of these hormones parallel the activity of the sympathetic nervous system especially under extreme conditions such as sever hemorrhage and brain ischemia. Endothelin level increased in certain diseases such as toxemia of pregnancy, acute renal failure and chronic uremia causes renal vasoconstriction and decrease GFR.
• Angiotensin II: constrict efferent arterioles lead to increase GFR.
• Endothelial-derived Nitric Oxide: decrease renal vascular resistance and increase RBF and GFR.
• Prostaglandin and Bradykinin: tend to increase GFR.
3. Auto-regulation of GFR and renal blood flow:
It is intrinsic mechanism by which the kidneys normally keep renal blood flow and GFR relatively constant, despite marked changes in arterial blood pressure.
Normally GFR is about 180 L/ day and tubular reabsorption is 178.5 L / day, leaving 1.5 L / day of fluid excreted in the urine. In the absence of autoregulation a relatively small increase in blood pressure (100?125 mmHg) would cause an increase in GFR (180?225 L/ day) if tubular reabsorption remained constant at (178.5 L/day), this increase urine flow to 46.5 L/day, increase in urine of more than 30 fold. This change would quickly deplete the blood volume,
but such change in arterial pressure exert less effect on urine volume…How?
There are negative feedback mechanism provide the degree of GFR and renal blood flow that is required. These mechanisms are:
1. Tubuloglomerular mechanism: Which occur through:
A. The afferent arteriolar vasodilator feedback mechanism:
In cases of low GFR (for any causes like dehydration, hypervolemia) causes a low flow rate of tubular fluid which lead to over absorption of Na and Cl ions in ascending limb of the loop of Henle and decrease the ion concentration at the macula densa, this decrease in ion concentration initiates a signal from the macula densa to dilate the afferent arteriole with result to an increased blood flow into glomerulus causing an increase in glomerular pressure and GFR back toward the required level.
B. The efferent arteriolar vasoconstrictor feedback mechanism:
In cases of low Na an Cl ions at the macula densa cause stimulation for Juxtaglomerulus cells to release renin, this in turn causes the formation of angiotensin II, which constrict efferent arterioles more than afferent arterioles, cause increase the pressure in glomerulus and this leading to increase in GFR back to normal.
NOTE: Renin is an enzyme that release from renal Juxtaglomerular cells and act on angiotensinogen. It increase if: Renal perfusion pressure and renal blood flow is decreased and in stimulation of renal nerve.
2. Myogenic mechanism: When arterial pressure rises, stretches the wall of the arteriole, this in turn causes a secondary constriction of the arteriole, this decreases the renal blood flow and GFR back toward normal. When pressure falls too low, allows the artery to dilate and therefore increase the blood flow and GFR. An example of such auto-regulatory mechanism is when arterial hypotension occurs or when human become dehydrated.
Renin-angiotensin is activated to conserve water and salt while allowing the waste products to be excreted.