In this article we will discuss about:- 1. Meaning of Glomerular Filtration Rate 2. Advantages 3. Determinants 4. Forces Affecting 5. Estimation.
Meaning of Glomerular Filtration Rate (GFR):
Amount of filtrate formed by both kidneys together in unit time is called GFR. It is about 20% of the renal plasma flow.
Normal value is 125 ml/min or 180 L/day.
It is determined by:
a. The balance of hydrostatic and colloid pressures across the capillary membrane
b. The capillary filtration coefficient (Kf). It is the product of permeability and filtering surface area of the capillaries.
Advantages of High Glomerular Filtration Rate:
i. High GFR is necessary to remove waste products that are filtered but poorly reabsorbed.
ii. High GFR makes it possible for entire plasma volume to be filtered 60 times per day, if plasma is 3 L with GFR 180 L/day.
Filtration Fraction (FF):
It is the fraction of renal plasma flow that is filtered at the glomerulus.
FF = GFR/RPF = 0.20
Glomerular Capillary Membrane:
This membrane is similar to any other capillary membrane having three layers:
a. The Endothelium of the Capillary:
This is perforated by thousands of small holes called fenestrae which are large but negatively charged hindering the passage of plasma proteins.
b. A Basement Membrane:
It consists of a meshwork of collagen and proteoglycan that have large spaces through which solutes and water pass through.
c. A Layer of Epithelial Cells:
These cells are not continuous but have long foot like processes (podocytes). The foot processes are separated by slit pores through which glomerular filtrate moves.
The glomerular capillary membrane is thicker but more porous filtering more fluid at a higher rate. The filterability of solutes is inversely proportional to the size. Normally, molecules with 4 nm diameter pass easily. Between 4-8 nm filtered with difficulty. Above 8 nm molecules are not filtered. A filterability of 1.0 means substance is freely filtered as water. If it is 0.75 means substance is filtered only 75%. Na+ and glucose are freely filtered.
The electrical charges affect the filtration. The negatively charged large molecules are filtered less easily than positively charged molecules of equal size, e.g., albumin which is 6 nm in diameter is not filtered due to its negative charge. Neutral dextran’s are filtered better than negatively charged dextran’s the reason being negativity of the basement membrane repels negatively charged molecules.
Determinants of Glomerular Filtration Rate:
It is determined by:
1. The sum of hydrostatic and colloid osmotic pressures across the glomerular membrane which gives net filtration pressure (NFP).
2. The filtration coefficient (kf).
GFR = Kf × NFP
Forces Affecting Glomerular Filtration Rate:
NFP = +10 mm Hg
Kf = GFR/NFP, where kf → filtration coefficient
GFR = Kf × NFP (PG – PB – G + B)
Summary of Factors that can Decrease GFR:
1. Filtration Coefficient (Kf):
Since the GFR is 125 ml/min and NFP is 10 mm Hg, normal Kf is calculated as 12.5 ml/min/mm Hg.
Factors Affecting Glomerular Filtration:
i. Filtering membrane—size, pores and charge.
ii. Particle—size, shape, charge.
iii. Filtering forces.
iv. Amount of blood flow.
When there is a rapid rate of blood flow effective filtration pressure and GFR increases. Conversely, slow rate of blood flow reduces GFR.
i. Autoregulation:
a. Tubuloglomerular feedback
b. Myogenic mechanism.
ii. Mesangial Cells:
The contraction of mesangial cells compresses the glomerulus and reduces the surface area of glomerular membrane which is normally 0.8 m2.
iii. Sympathetic Nerves:
Strong stimulation of sympathetic system constricts the renal arterioles and decreases renal blood flow and GFR. Mild and moderate stimulation has little influence.
iv. Other factors like high protein diet and increased blood glucose increases renal blood flow and GFR.
Regulation of Glomerular Filtration and Renal Blood Flow:
1. Autoregulation.
2. Sympathetic nervous system.
3. Hormonal control.
1. Autoregulation:
Two Mechanisms:
i. Myogenic mechanism.
ii. Tubuloglomerular feedback.
i. Myogenic Mechanism:
When blood flow to the kidneys increases, it stretches the smooth muscle lining the blood vessel wall.
Renal blood flow increases → Stretches smooth muscle of blood vessel wall → Increases intracellular ca++ in smooth muscle → Contraction of smooth muscle → Vasoconstriction of renal blood vessels → Renal blood flow decreases.
ii. Tubuloglomerular Feedback (TGF) Mechanism:
Alteration of tubular flow NaCl is sensed by the macula densa of the Juxtaglomerular apparatus and produces a signal renin that alters GFR.
2. Sympathetic Nervous System:
Sympathetic stimulation → constriction of renal arterioles → decreases RBF and GFR.
3. Hormonal Control:
i. Norepinephrine, epinephrine and endothelin → constricts afferent and efferent arterioles causing decreased GFR and RBF.
ii. Endothelin derived nitric oxide → decreases renal vascular resistance → increases GFR.
iii. Angiotensin II ― Constricts efferent arteriole increases GFR → increases Na and water reabsorption due to reduced flow in peritubular capillaries.
iv. Prostaglandins and bradykinin cause vasodilation and increases GFR and blood flow.
Estimation of Glomerular Filtration Rate:
Renal clearance of a substance is the volume of plasma that is completely cleared of the substance by the kidneys per unit time.
Cs = Us × V/Ps
Cs = Clearance of the substance
Us = Substance present in urine
V = Volume of urine passed per day
Ps = Substance present in plasma.
1. Inulin Clearance (Fig. 8.16):
A substance commonly used is inulin, a polysaccharide molecule with a molecular weight of about 5200. Inulin is not produced in the body, is found in the roots of certain plants and must be administered intravenously. It is nontoxic, only filtered not reabsorbed. It is costly and not easily available. Inulin clearance is taken as gold standard since its value almost equals GFR value.
2. Creatinine Clearance Test:
Other substances used are creatinine and radioactive iodothalamate. Creatinine is synthesized from muscle creatine with in the body so it need not be administered intravenously. Since creatinine is secreted in pars recta, it over estimates GFR. The range of creatinine clearance is wide between 70 and 140 ml/min depending on the muscle mass.
3. Urea Clearance Test:
Urea is the end-product of protein metabolism. It is partly reabsorbed by the renal tubules, so urea clearance is less than GFR. It is influenced by the protein content of the diet.
4. Maximal Urea Clearance:
U × V/P Normal values = 75 ml/min.
This is applicable when urine output is more than 2 ml/min.
U = Urea concentration in urine (mg/ml)
V = Volume of urine excreted (ml/min)
P = Urea concentration in plasma (mg/ml)
5. Standard Urea Clearance:
U × √V/P Normal values = 54 ml/min.
This is applicable when the urine volume is less than 2 ml/min.
Comparisons of Inulin Clearance with Clearance of Different Solutes:
1. If the clearance rate of the substance equals that of inulin, the substance is only filtered and not reabsorbed or secreted.
2. If the clearance of the substance is less than inulin clearance, the substance must have been absorbed by the nephron tubules.
3. If the clearance is greater than that of inulin clearance, substance must have been secreted by the tubules.