Tubular secretion of PAH

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Tubular secretion of PAH

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USMLE® Step 1 style questions USMLE

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A group of researchers is examining the relative concentrations of several substances along the proximal convoluted tubule. They discover one substance that can be used to approximate renal plasma flow. This substance is denoted by which of the following lines detailed in the graph below?  


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If we take a cross-section of the kidney, there are two main parts, the outer cortex and the inner medulla.

If we zoom in, there are millions of tiny functional units called nephrons which go from the outer cortex down into the medulla and back out into the cortex again.

These nephrons perform the major function of the kidney, which is to clear harmful substances from the body by filtering the blood.

Each nephron is made up of the glomerulus, or a tiny clump of capillaries, where blood filtration begins.

Interestingly, once the blood leaves these glomeruli it does not enter into venules. Instead the glomerulus funnels blood into efferent arterioles which divide into capillaries a second time.

These peritubular capillaries then reunite and at that point the blood enters venules and eventually drains back into the venous system.

Now, when blood gets filtered, some fluid remains in the glomerulus, and some fluid goes into the renal tubule.

The renal tubule is a structure with several segments: the proximal convoluted tubule, the U- shaped loop of Henle with a descending and ascending limb and the distal convoluted tubule, which winds and twists back up again, before emptying into the collecting duct, which collects the final urine.

Now, zooming in on this nephron’s tubule, each one’s lined by brush border cells which have two surfaces. One is the apical surface which faces the tubular lumen and is lined with microvilli, which are tiny little projections that increase the cell’s surface area to help with solute reabsorption.

The other is the basolateral surface, which faces the peritubular capillaries, which run alongside the nephron.

Alright, now, one substance that’s filtered out of the glomerulus and into the tubule is para-aminohippuric acid, or PAH for short.

Actually, PAH is an organic acid, and about 90% is bound to plasma proteins. So, really, only the unbound 10% can pass through the glomerular capillaries.

Essentially, the higher the unbound PAH concentration, the more PAH will get filtered.

If we wanted to illustrate this in a graph, with the unbound PAH concentration in the blood on the x axis and the PAH filtered on the y axis, we would see that as the unbound concentration of PAH increases, the filtered load of it is also going to increase in a linear fashion.

Summary

Para-aminohippuric acid (PAH) is a substance that is freely filtered by the glomeruli in the kidneys and secreted by the tubular cells into the tubular fluid. The secretion of PAH occurs primarily in the proximal tubule of the nephron and is facilitated by transporters located on the luminal surface of the tubular cells.

The amount of PAH that is secreted by the kidneys is used to estimate the renal blood flow, which is an important parameter in the assessment of kidney function. Since nearly all of the PAH that is filtered by the glomeruli is secreted by the tubular cells, the amount of PAH that is excreted in the urine is directly proportional to the amount of blood that is flowing through the kidneys.

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. "Luminal transport step of para -aminohippurate (PAH): transport from PAH-loaded proximal tubular cells into the tubular lumen of the rat kidney in vivo" Pflügers Archiv European Journal of Physiology (1997)
  6. "ATP-dependent para-aminohippurate transport by apical multidrug resistance protein MRP2" Kidney International (2000)
  7. "Effect of para-aminohippurate on renal transport of oxalate" Kidney International (1979)
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