Factors affecting filtrationRegulation of filtrationAutoregulation of renal blood flowMeasuring filtrationEstimating filtration

You might need to read the nephron overview section as well. Kidneys are complicated.

Factors affecting filtration

In normal, day to day function, the rate of glomerular filtration is determined by kidney perfusion. However, changes to the composition of blood, or obstruction of the urinary tract can also influence the rate of filtration. For filtration to occur at all, the pressure of blood in the glomerular capillaries must exceed two other forces at play: the osmotic force that proteins retained with the capillary exert, and the pressure of fluid within Bowman’s capsules (Figure 1).

glomerular filtration

Figure 1: Glomerular filtration occurs because blood pressure within the glomerular capillary is greater than the apposing effects of the osmotic pull of proteins within the capillary (πGC) and the pressure of filtrate within the Bowman’s capsule (PBC). In the example above, if PGC fell to 45 mmHg, no filtration would occur. You’ll find that different textbooks give slightly different estimates of PQC, PBC and πGC, but they are usually within about 5 mmHg of each other.

By the time blood has reached the afferent arteriole, the effect of vascular resistance has reduced blood pressure to about 60 mmHg. Usually, this pressure is sufficient to overcome the forces acting in the opposite direction and filtration occurs at a pressure of about 15 mmHg. From this, it’s clear that a small drop in blood pressure will significantly reduce filtration. This is why a decline in urine output is an important symptom; it suggests low blood pressure and/or low blood volume.

Obstruction (even if partial) of the urinary tract anywhere between the proximal convoluted tubule and the bladder will also affect glomerular filtration. Such an obstruction will cause increased back pressure in the Bowman’s capsule (PBC), opposing filtration. Finally, when plasma protein is in excess (e.g. in dehydration), πGC will increase reducing filtration as well. When you consider that dehydration low blood pressure as well, it is clear why something so simple as a lack of fluid can cause renal failure.

Regulation of glomerular perfusion

From the above, it is clear that pressure within the glomerular capillaries is crucial for filtration to occur. Indeed, the regulation of the glomerular filtration rate (GFR) is controlled by changes in the diameter of the afferent and efferent arterioles. We can make a simple model of how each arteriole contributes to GFR using a leaky garden hose. The leak represents GFR, while the hose on either side represents the afferent and efferent arterioles (Figure 2).

Figure 2: : Think of the glomerulus being a leak in a garden hose through which water is flowing. Some of the water leaks out on either side of the afferent and efferent sides. If you press down with your foot on the afferent side (= afferent arteriole constriction), flow beyond that point is reduced and the hose leaks less. On the other hand, if you occlude the efferent side of the hose, pressure builds up upstream and the amount leaking out increases. In either case, pressure increases upstream of the obstruction.

A garden hose doesn’t dilate, so we’ll just have to remember that the effect of dilation of either arteriole is simply the opposite of constriction. So, dilation of the afferent arteriole will increase GFR and dilation of the efferent arteriole will decrease GFR.

Glomerular perfusion is regulated by:

  • The sympathetic nervous system innervating the arterioles
  • Circulating hormones such as angiotensin II and adrenaline
  • Autoregulation of glomerular blood flow (see below)

Autoregulation of glomerular blood flow

The kidney regulates its own blood flow over a wide range of perfusion pressures by contracting afferent arterioles when pressure increases. This allows the kidney to maintain constant GFR, despite swings in blood pressure due to other activities in the body (like going for a jog).

Figure 3:: The relationship between renal perfusion pressure and renal blood flow. Across the range of typical and slightly hypo/hypertensive pressures, renal blood flow is pretty constant, due to the autoregulation of renal perfusion. At quite high perfusion pressures, autoregulation is overcome and flow increases. Autoregulation occurs because the afferent arterioles contract when pressure increases.

Autoregulation of GFR probably also protects the kidney from high blood pressure as well. Two mechanisms are at work to produce this effect. Firstly, afferent arterioles respond to changes in wall stretch by contracting. Secondly, the cells in the macula densa releases adenosine in response to increased Na+ in the proximal tubule, which causes vasoconstriction of the nearby afferent arteriole. When GFR is excessive, there is insufficient time for Na+ absorption in the tubules, resulting in a higher concentration of this ion. This mechanism is part of the body’s system for regulating Na+.

Measuring glomerular filtration rate

We can work out GFR by comparing the concentration of solutes in urine and in blood. This is how renal clearance of different drug metabolites is usually calculated, and differs from molecule to molecule. Renal clearance is volume of plasma from which substance is completely removed per unit time. In principle, for GFR to be calculated from the renal clearance of a molecule, we’d need to choose a molecule that is completely filtered but neither reabsorbed from, nor secreted into, the renal tubules. Unfortunately, the body does not utilise or produce such a molecule (everything is reabsorbed or secreted to some extent), so to really accurately determine GFR, we’d need to inject something synthetic. In the past, the synthetic polysaccharide inulin (not insulin [LINK]) has been used for this purpose, but this less commonly performed today. It is far simpler to use a molecule that is produced by the body, and which nearly meets our stringent criteria for filtration without reabsorption or secretion. The metabolite creatinine just about fits the bill. Creatinine is completely filtered, not reabsorbed, although a small amount is secreted into renal tubles. Using creatinine slightly overestimates GFR because of this tubular secretion: there’s a tiny bit more creatinine in urine than simple filtration alone can account for. Clinically, this slight overestimation isn’t of enormous consequence.

The renal clearance of any other molecule can be calculated by diving the mass secreted in urine, by the plasma creatinine concentration:

Now, the mass of a substance secreted by the kidneys is the product of its concentration in urine and the volume of urine produced over a certain time. We can alter the equation above slightly to account for this:

Because we are assuming that renal clearance of creatinine is pretty much exclusively through filtration (rather than secretion), clearance of creatinine equals GFR.

The amount of creatinine in plasma is usually around 700 mg/L, while urine contains about 10 mg/L. Urine production is about 100 mL/hr, or 0.1 L/hr. So, GRF is:

That’s 170 L/day, or 56 time typical plasma volume (3L). Here is some testimony to the power of the kidneys to retain fluid under normal circumstances.

Estimating glomerular filtration rate (eGFR)

In practice, can be combersome to measure both urinary and plasma creatinine levels. GFR can be estimated from plasma creatinine levels alone, using equations based on large population data. One popular equation is the Modification of Diet in Renal Disease (MDRD) formula:

Fortunately, there are machines to do this calculation for you.

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