Glomerular filtration

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Glomerular filtration

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Glomerular filtration

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USMLE® Step 1 style questions USMLE

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To understand the process of glomerular filtration, a group of researchers examine several molecules which cannot undergo filtration. One molecule that does not undergo filtration is albumin. Which of the following contributes to the glomerulus' inability to freely filter albumin?  

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The workhorses of the urinary system are the kidneys which are the twin, bean-shaped organs in your body that clear harmful substances by filtering blood - like a water purification plant that helps clean the drinking water for a city.

Blood filtration happens inside the over a million nephrons scattered inside each kidney, and each nephron is made up of a renal corpuscle and a renal tubule.

So let’s zoom in on the renal corpuscle, which is where blood filtration starts.

The renal corpuscle is made up of the glomerulus - a tiny bed of capillaries - and the Bowman’s capsule surrounding the glomerulus.

Between the glomerulus and Bowman’s capsule there’s a space called Bowman’s space.

Blood gets to the glomerulus through the afferent arteriole, but interestingly enough, once the blood leaves the glomerulus, it doesn’t enter into venules.

Instead the glomerulus funnels blood into efferent arterioles which divide into capillaries a second time.

These capillaries are called peritubular capillaries - because they are arranged around the renal tubule.

Now, the first step in blood filtration happens at the glomerular filtration barrier.

The glomerular filtration barrier is made up of three layers and together they separate the blood inside the glomerular capillaries from the fluid inside Bowman’s capsule.

They work like a sieve, allowing water and some solutes in the plasma like sodium, to pass into Bowman’s space, while keeping red blood cells and plasma proteins in the blood.

Starting from the capillary lumen, the first layer of the glomerular filtration barrier is the endothelium, made up of glomerular capillary endothelial cells.

These cells have fenestrations, which are like pores in the cell themselves, tiny spots where the cytoplasm isn’t filled in so that solutes and proteins can pass right through. But the fenestration are tiny so they block red blood cells from passing through.

Blood minus red blood cells is plasma - so plasma gets to the second layer of the glomerular filtration barrier, which is the basement membrane.

The basement membrane is a gel-like layer with tiny pores and this layer prevents plasma proteins from passing through. That’s because the pores are too tiny for plasma proteins to slip through, and because the basement membrane has a negative electric charge, which repels the negatively charged plasma proteins.

The third layer of the glomerular filtration barrier is the epithelial layer, which is made of special cells called podocytes that wrap around the basement membrane like the tentacles of an octopus. Between these tentacle-like projections are tiny gaps called filtration slits. This third layer works with the basement membrane to block the passage of plasma proteins.

Fluid that makes it past all three of these layers is called glomerular filtrate.

Now, the volume of fluid that gets through the glomerular filtration barrier is ultimately governed by Starling forces.

Starling forces include both the hydrostatic pressures, which are fluid pressures, as well as oncotic pressures, which are pressures based on the amount of protein, that are present on either side of the barrier.

Since there are no proteins in Bowman’s space, there’s are only three Starling forces at play: the hydrostatic pressure of capillary blood, pushing against the endothelium of the barrier, which we’ll refer to as Pgc; the hydrostatic pressure of filtrate in Bowman’s space, which we’ll refer to as Pbs; and the oncotic pressure determined by the concentration of proteins in capillary blood - referred to as ℼ gc.

Together, these three pressures determine the net ultrafiltration pressure of the glomerulus, which is the difference between the force favoring filtration, Pgc, and the two forces opposing filtration, Pbs + ℼ gc. So the net ultrafiltration pressure is that gives us Pgc - (Pbs + ℼ gc).

Now, let’s think about the net ultrafiltration pressure at different points along a glomerular capillary.Early on in the capillary, right around where blood flows in from the afferent arteriole, oncotic pressure is at its lowest, because the capillary is still full of fluid and that means that the protein concentration is relatively low.

Key Takeaways

Glomerular filtration is a process by which blood plasma is filtered through the glomerular filtration membrane. This is the first step of urine formation, by which the kidney starts to eliminate toxins from blood plasma. The glomerular filtration membrane has tiny pores allowing only small elements to pass, and ideally spare large molecules such as albumin and blood cells.

Sources

  1. "Medical Physiology" Elsevier (2016)
  2. "Physiology" Elsevier (2017)
  3. "Human Anatomy & Physiology" Pearson (2018)
  4. "Principles of Anatomy and Physiology" Wiley (2014)
  5. "What Is the Glomerular Ultrafiltration Barrier?" Journal of the American Society of Nephrology (2018)
  6. "Cell Biology of the Glomerular Podocyte" Physiological Reviews (2003)
  7. "Mechanical challenges to the glomerular filtration barrier: adaptations and pathway to sclerosis" Pediatric Nephrology (2016)