A Lay Person's Guide to Glomerular Function

The simplified view of an incredibly complex process

Home Base - The Nephron
The complexity of the human kidney can be expressed in but a few statistics. The organ measures just four inches long and weighs a mere five ounces, yet it holds one million filtering units that can be seen only with a high-powered microscope. These units are called nephrons.

Nephrons are the key to the kidney's filtering process, processing a constant flow of waste-laden blood and sorting out the vital fluids, proteins and nutrients (which are returned to the bloodstream) from the toxic and unnecessary elements (which are collected as urine and forwarded toward the bladder for removal from the body.)
Nephrons hold countless mysteries both for physicians specializing in kidney ailments (called nephrologists) and scientists who spend their entire careers trying to figure out exactly how the tiny nephron works and how to fix it when it falters.

Experts are sure of a number of reasons the kidney filtering process goes wrong, including high or low blood pressure, which can damage nephrons. Kidneys can develop cysts or cancer or inflammations.

But unknown thus far is why tens of thousands of children and young adults are affected by processing problems that causes protein to escape through the filtering unit that is supposed to recycle it. In a disease such as Minimal Change Nephrotic Syndrome, much of the protein is lost in the urine and the patient suffers from edema (swelling) in various parts of the body, and high cholesterol levels.

A more serious threat to the filtering mechanism occurs in instances of Focal Segmental Glumerulosclerosis (FSGS), in which the damage to the filtering unit is so great that the one part of the nephron, the glomerulus, is scarred. FSGS can progress to such a level that the kidney fails. FSGS may sometimes accompany Nephrotic Syndrome or even cause it, but the relationship between the two is not fully understood.

Key Players -- Glomeruli and Podocytes
The graphic nearby shows the two elements making up the nephron - the tubule and the glomerulus. The tubule is a long tube that at one point expands into a bulb-like section known as Bowman's capsule. Within this capsule is the glomerulus, a collection of capillaries stemming from branches of the renal artery where blood is received for filtration.

(Of course, the actual scene inside a live kidney, nowhere as organized as this, has tubules and capsules crammed together in what seems like a jumbled mish-mosh. Miraculously, though, each nephron operates independently as a single unit.)

Here is a close up view of the nephron, showing the glomerulus inside Bowman's capsule.
The first filtering process occurs as the blood flows through the collection of capillaries known as the glomerulus. The structure of the extremely small capillaries includes several layers of tissue (including something called the basement membrane) through which the blood can seep. The blood, at this point, carries a great many materials, including glucose, water and important amino acids.

Not shown in the nephron diagram is the tiny but powerful "star" of current research, a major filtering cell called the podocyte. This cell sits on the outside of the basement membrane on the exterior of the glomerulus. The podoctye consists of a main body from which extend many branch-like feet (called foot processes) that sprawl out into secondary and tertiary branches. These tertiary feet, or pedicels, interlock with pedicels from other podocytes and create a sprawling lacework around the glomerulus that plays a large role in filtering the blood traveling through the glomerulus.

Here is a photo of a podocyte taken with a high-powered microscope.

Between the microscopic openings that occur within this dense network of pedicels are the slit diaphragms through which the blood from the glomerulus gets filtered.

Even though the blood that gets filtered out of the glomerulus into Bowman's capsule includes many valuable components such as water, glucose, protein and mineral salts, the body has no intention of allowing all of them to escape into the urine. Instead, the captive fluid flows from the capsule through a long renal tubule that is surrounded by many thousands of capillaries. In an incredibly sophisticated process, most of the water and valuable materials in the tubule are reabsorbed into the capillaries and distributed back into the bloodstream.

The waste materials remain in the tube and make their way down through the kidney into the bladder.

When Things Go Wrong and the Glomerulus Is Injured
In conditions such as Nephrotic Syndrome, the filtration system created by the branches or foot processes of the podocytes somehow malfunctions. The protein that is supposed to remain in the blood is lost through the filter, enters Bowman's capsule and winds up in the urine that collects in the bladder.

The breakdown in the filtration process is also thought responsible for Focal Segmental Glomerulosclerosis (FSGS), in which the glomerulus is scarred and, in the most severe form, is destroyed. When this scarring is replicated throughout the kidney, the organ ceases to function.

Scientists now are focusing on the podocyte as the possible key to understanding the filtration malfunction that is related to Nephrotic Syndrome and FSGS. Researchers have discovered certain proteins in the structure of the podocyte which, when they are altered or missing, cause FSGS.

To better understand the implications of this research and the importance of the podoctye, see research update.