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Renal physiology: Glomerular filtration

What is glomerular filtration?

Glomerular filtration is the first step in making urine. It is the process that your kidneys use to filter excess fluid and waste products out of the blood into the urine collecting tubules of the kidney, so they may be eliminated from your body.

Why we make urine

Unless things go wrong, most of us don’t spend much time thinking about what it takes to urinate, but in fact, your kidneys and urinary system are quite amazing. Together they receive over a liter of blood each minute, and eliminate around 1.5 litres of urine per day, efficiently getting rid of excess water and waste products that would otherwise cause you some serious problems.
Your body metabolizes (processes) the things you eat and drink, which produces energy, as well as the various building blocks that you need to keep your tissues and organs healthy. While doing this, a variety of other substances are produced that can’t be used or stored for later and must be eliminated to prevent toxic build-up. In addition to waste products, our diets often contain substances in amounts that are far more than we need on a day-to-day basis (such as carbohydrates and fats). You get rid of non water-soluble waste products in feces (e.g., undigested fibre and bacteria), and water-soluble waste products in urine (e.g., urea and electrolytes - sodium and potassium). Some foods and medications can change the colour of your urine; e.g., beets, blackberries and rhubarb can turn urine red or pink. This is evidence that your kidneys are eliminating the colourful soluble pigments from your body.
The main substances excreted in urine are:
  • metabolic waste products - e.g., urea and creatinine
  • electrolytes - inorganic compounds (including sodium, potassium, calcium, chloride and bicarbonate) that your body uses to control the fluid content inside your body fluids
  • water
You can think of your kidneys as being your body’s natural blood filter. They are able to control the amount of water and substances dissolved in your body fluids (solutes) by reabsorbing what you need and producing urine to get rid of the rest. The production of urine is obligatory, meaning that it is made regardless of what is going on with your body; for example, you still make urine even when you are severely dehydrated. This occurs because of the need to remove various solutes from the body in order to keep internal conditions stable and relatively constant (homeostasis), so that your all of your body’s physiological processes continue operating effectively. Making urine is a complicated process, and to do it, each of your kidneys contain around a million specialized structures, called nephrons.
Figure of urinary system and a nephron

How glomerular filtration works

The first step in making urine is to separate the liquid part of your blood (plasma), which contains all the dissolved solutes, from your blood cells. Each nephron in your kidneys has a microscopic filter, called a glomerulus that is constantly filtering your blood.
Blood that is about to be filtered enters a glomerulus, which is a tuft of blood capillaries (the smallest of blood vessels). The glomerulus is nestled inside a cup-like sac located at the end of each nephron, called a glomerular capsule. Glomerular capillaries have small pores in their walls, just like a very fine mesh sieve. Most capillary beds are sandwiched between arterioles and venules (the small vessels delivering blood to and collecting blood from capillary beds), and the hydrostatic pressure drops as blood travels through the capillary bed into the venules and veins.The glomerulus, on the other hand, is sandwiched between two arterioles - afferent arterioles deliver blood to the glomerulus, while efferent arterioles carry it away. Constriction of efferent arterioles as blood exits the glomerulus provides resistance to blood flow, preventing a pressure drop, which could not be achieved if blood were to flow into venules, which do not really constrict. The two arterioles change in size to increase or decrease blood pressure in the glomerulus. In addition, efferent arterioles are smaller in diameter than afferent arterioles. As a result, pressurized blood enters the glomerulus through a relatively wide tube, but is forced to exit through a narrower tube. Together, these unique features plus the fact that your heart is supplying your kidneys with over a liter of blood per minute (around 20% of its output) maintain a high glomerular capillary pressure and the filtration function of the kidney, regardless of fluctuations in blood flow. For example, the sympathetic nervous system can stimulate the efferent arteriole to constrict during exercise when blood flow to the kidney is reduced.
The physical characteristics of the glomerular capillary wall determine what is filtered and how much is filtered into the glomerular capsule. Working from the inside out, the capillary walls are made up of three layers:
  • Endothelium - this has relatively large pores (70-100 nanometers in diameter), which solutes, plasma proteins and fluid can pass through, but not blood cells.
  • Basement membrane - this membrane is also made up of three layers, and is fused to the endothelial layer. Its job is to prevent plasma proteins from being filtered out of the bloodstream.
  • Epithelium - this layer consists of specialized cells called podocytes. These cells are attached to the basement membrane by foot processes (pedicels). They wrap around the capillaries, but leave slits between them, known as filtration slits. A thin diaphragm between the slits acts as a final filtration barrier before the fluid enters the glomerular space.
Figure of glomerular capillary wall consisting of the endothelium, basement membrane, and epithelium
Together the glomerulus and glomerular capsule filtering unit are known as a renal corpuscle.
Figure of a renal corpuscle
In addition to the unique glomerular capillary bed, the kidneys have other specialized capillaries, called peritubular capillaries that are tiny blood vessels that run parallel to and surround the proximal and distal tubules of the nephron, as well as the loop of Henle, where they are known as the vasa recta. The vasa recta is important for countercurrent exchange, the process that concentrates urine.

The glomerular filtration rate

The rate at which kidneys filter blood is called the glomerular filtration rate. The main driving force for the filtering process, or outward pressure is the blood pressure as it enters the glomerulus. This is counteracted to some extent by inward pressure due to the hydrostatic pressure of the fluid within the urinary space, and the pressure generated by the proteins left in the capillaries that tend to pull water back into the circulatory system (colloidal osmotic pressure). The net filtration pressure is the outward pressure minus the inward pressure.
Figure of a glomerular capsule with glomerular hydrostatic pressure, blood colloid osmotic pressure, and capsular hydrostatic pressure

How is the glomerular filtration rate regulated?

It is perfectly normal for your blood pressure to fluctuate throughout the day; however, perhaps surprisingly, this has no effect on your glomerular filtration rate. This is because under normal circumstances, your body can precisely control it:
Intrinsic mechanisms:
  • Renal autoregulation - the kidney itself can adjust the dilation or constriction of the afferent arterioles, which counteracts changes in blood pressure. This intrinsic mechanism works over a large range of blood pressure, but can malfunction if you have kidney disease.
Graph of renal autoregulation occurring between 80 and 160mm Hg mean arterial pressures
Extrinsic mechanisms:
  • Neural (nervous system) control and hormonal control - these extrinsic mechanisms can override renal autoregulation and decrease the glomerular filtration rate when necessary. For example if you have a large drop in blood pressure, which can happen if you lose a lot of blood, your nervous system will stimulate contraction of the afferent arteriole, reducing urine production. If further measures are needed your nervous system can also activate the renin-angiotensin-aldosterone system, a hormone system that regulates blood pressure and fluid balance.
  • Hormonal control - atrial natriuretic peptide is a hormone that can increase the glomerular filtration rate. This hormone is produced in your heart and is secreted when your plasma volume increases, which increases urine production.

Consider the following:

Creatinine is a waste product of creatine metabolism. It is produced in muscle when creatine is metabolised to generate energy. Creatinine is not reabsorbed or secreted, but is exclusively filtered through the kidneys, so its rate of excretion from your bloodstream is directly related to how efficiently your kidneys are filtering. By measuring the amount of creatinine in a sample of your blood, and combining this with other information such as your age, ethnicity, gender, height and weight, your doctor is able to estimate your glomerular filtration rate (GFR), which can give them a good idea of how well your kidneys are working.
Chart showing glomerular filtration rate indicating kidney failure, kidney disease, and normal function

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