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In: Anatomy and Physiology

Discuss the mechanisms involved in the formation of the glomerular filtrate, its composition and the regulation...

Discuss the mechanisms involved in the formation of the glomerular filtrate, its composition and the regulation of its rate of formation, the GFR.

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Expert Solution

All blood in the body flows through the kidneys hundreds of times each day. The kidneys push the liquid part of blood through tiny filters (called nephrons), then reabsorb most of the fluid back into the blood. The fluid and waste products that the kidneys don't reabsorb are excreted as urine.

The rate of blood flow through the kidneys is the glomerular filtration rate, or GFR. (The glomeruli are microscopic bundles of blood vessels inside nephrons, and are crucial parts of the filtering system.) The glomerular filtration rate can't be measured directly -- that's where measuring creatinine and creatinine clearance comes in.

Blood entering the glomerulus has filterable and non-filterable components. Filterable blood components include water, nitrogenous waste, and nutrients that will be transferred into the glomerulus to form the glomerular filtrate.

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.

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.

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.

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