Glomerular Filtration Rate



The rate at which plasma is filtered (measured in ml/min) is known as the glomerular filtration rate (GFR). Filtration is a non-specific process of bulk flow: water and small molecular weight substance move from the glomerular capillaries, across the filtration membrane, and enter Bowmanís space. Roughly 20% of the total volume of plasma flowing through the glomerular capillaries is filtered. Because filtration involves bulk flow, the concentration of a substance in Bowmanís space is the same as its concentration in the plasma.

Why does filtration occur? Filtration occurs because of the high pressure in the glomerular capillaries (PGC). The glomerular capillaries are unique in that they lie between two arterioles, the afferent arteriole and the efferent arteriole. Because of the added resistance of the efferent arteriole, PGC is higher than pressure in a typical capillary.

The figure illustrates the forces that determine the filtration rate. The pressure in the glomerular capillaries, PGC, favors filtration. Opposing filtration is the osmotic pressure due to the blood proteins (πGC) and the hydrostatic pressure in Bowman's space (PBS). The net glomerular filtration pressure is the sum of these forces.


Measures of GFR (see lab)

In a single nephron, the rate of filtration is a function of the net filtration pressure, the permeability of the filtration membrane, and the surface area available for filtration. The measured GFR reflects these factors, and of course, the total number of functioning nephrons. Average GFR is 130 ml/min for a healthy young man, or 110 ml/min for a healthy young woman. (As well, GFR may be normalized to body surface area to account for individuals of different sizes).  The threshold for the definition of chronic kidney disease is defined as a GFR of less than 60 ml/min.  A GFR below 60ml/min is associated with an increased risk of progression of kidney disease, and in particular, an increased risk of death from cardiovascular disease.

GFR is directly measured by measuring the inulin clearance. Inulin is a plant carbohydrate that is neither reabsorbed nor secreted, thus the inulin clearance (volume of blood per unit time from which inulin is removed) is completely due to filtration. However, because inulin must be infused, in practice it is simpler to gauge kidney function by looking at an endogenous substance, namely creatinine, a metabolic breakdown product of skeletal muscle creatine. The creatinine clearance can be used to estimate the GFR. Alternatively, just the serum creatinine (plasma concentration of creatinine) may be measured to monitor kidney function.

In general, any factor that reduces the number of nephrons can over time reduce the GFR. GFR normally declines with age, but this decline occurs much more rapidly in individuals with chronic kidney disease. For instance, proteinuria, which is a common feature in various kidney diseases, leads to decreased GFR because protein in the filtrate causes inflammation and scarring in the renal tubules with subsequent nephron loss. Another way that GFR can decline in kidney disease is through the loss of surface area available for filtration. In glomerulosclerosis (a typical feature of diabetic nephropathy) there is increased extracellular material in the glomerulus, which decreases the surface area of the glomerular capillaries. 


Regulation of GFR

renal
        autoregulationOne would think that changes in the systemic blood pressure would cause changes in PGC and thus, changes in the GFR. In healthy individuals, this does not occur because of renal autoregulation. Renal autoregulation involves feedback mechanisms intrinsic to the kidney that cause either dilation or constriction in the afferent arteriole so as to counteract blood pressure changes and keep a steady GFR. For instance, if the mean arterial pressure increases, renal autoregulation causes the afferent arteriole to constrict, preventing the pressure increase from being transmitted to the glomerular capillaries, and keeping the GFR from increasing. As shown in the graph, renal autoregulation normally operates to keep GFR steady over a wide range of blood pressures.  Note that renal autoregulation is disrupted in chronic kidney disease.


If blood pressure drops too low due to excessive fluid loss, then the sympathetic nervous system will override renal autoregulation. Sympathetic nerves innervate the afferent arteriole, causing smooth muscle contraction. The sequence of events is as follows: loss of ECF volume (due to hemorrhage, diarrhea or dehydration) causes a drop in mean arterial pressure (MAP). Decreased MAP activates arterial baroreceptors, which leads to sympathetic nervous system activation, afferent arteriole constriction, and decreased GFR.


(Another effect of the sympathetic nervous system is to stimulate renin secretion by the juxtaglomerular cells, activating the renin-angiotensin-aldosterone system (RAAS). The RAAS increases extracellular fluid volume by increasing sodium reabsorption. We will focus more on this later on when we study sodium balance).


Finally, the hormone atrial natriuretic peptide (ANP) is a factor that can increase GFR. ANP is a hormone that is produced in the heart and whose secretion increases in response to increased plasma volume. The effect of ANP is to promote natriuresis (increased sodium excretion), in part through increased GFR, and in part through effects on Na+ reabsorption.


Quick Quiz


Fill-in Answer Correct False Correct Answer
1. The pressure in the glomerular capillaries (PGC) is high because of the resistance to flow provided by the __________.
2. A blockage in urine outflow (perhaps due to nephrolithiasis) causes an increase in the pressure in Bowmanís space. How would this affect net glomerular filtration pressure and GFR? [increase or decrease]
3. The mean arterial pressure increases from 90 mmHg to 110 mmHg. What happens to prevent an increase in the pressure in the glomerular capillaries? [constriction of efferent arteriole, constriction of afferent arteriole, dilation of afferent arteriole]
4. Proteinuria causes a decrease in GFR because it induces inflammation and damage in the renal tubules, causing a decreased number of  ________.
5. Name the term that means increased sodium excretion in the urine.
6. In response to hemorrhage, which of the following is activated to cause a decrease GFR? [ANP secretion, sympathetic nervous system, renal autoregulation, proteinuria]


(Spelling must be correct)