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High Yield Notes
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When hypoxia occurs there is increased production of , which is the first step in erythropoietin synthesis.

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Content Reviewers:

Rishi Desai, MD, MPH

With erythropoietin, ‘-poietin’ means ‘to make’ and ‘erythro-’ refers to red blood cells, so erythropoietin is a hormone that stimulates the production of erythrocytes or red blood cells in the bone marrow.

Erythropoietin, or EPO, is produced in the kidneys, and to a lesser extent in the liver, and travels through the blood to the bone marrow where it stimulates immature cells to transform into mature red blood cells.

Every cell in the body uses oxygen for cellular respiration.

As we breathe, oxygen diffuses into the bloodstream where it binds hemoglobin within the red blood cells and gets carried off to various parts of the body.

Red blood cells live for about 120 days, so there is a constant need to produce new red blood cells.

Now, in the bone marrow, there are proerythroblasts, which are primitive or immature red blood cells.

The kidneys produce a constant level of erythropoietin, which gets released into the blood and makes its way to the bone marrow, where it binds to erythropoietin receptors on the immature red blood cells and causes them to erythrocytes, or mature into red blood cells, usually this production of erythropoietin is constant, so the production of mature red blood cells is constant.

If there’s ever decreased oxygen delivery to the tissues, then one thing the body can do is ramp up production of oxygen delivery vehicles, in other words red blood cells.

In this situation, the kidney cells ramp up production of erythropoietin, therefore ramping up production of mature red blood cells.

Interestingly, erythropoietin prevents immature red blood cells from killing themselves by apoptosis, meaning that without erythropoietin, developing red blood cells die via apoptosis.

Fundamentally, decreased oxygen delivery to the tissues can be due to a decrease in blood flow or a decrease in blood oxygen content.

If there’s a decrease in blood flow, then increasing the number of red blood cells is not effective, however, if there’s decreased oxygen content like for example with, then increasing the number of red blood cells will is effective and will help.

What’s neat is that the kidney can distinguish between these two situations.

A decrease in blood flow means that the kidneys are less perfused, and it leads to less fluid getting filtered in the glomeruli.

Less fluid filtered means less solutes need to be reabsorbed and saved from being urinated out by the tubular cells, which requires energy from oxygen.

But in this case since there’s less solutes to reabsorb, the demand for oxygen by those tubular cells is low.

  1. "Medical Physiology" Elsevier (2016)
  2. "Physiology" Elsevier (2017)
  3. "Human Anatomy & Physiology" Pearson (2018)
  4. "Principles of Anatomy and Physiology" Wiley (2014)
  5. "Erythropoietin" BMJ (1964)
  6. "Erythropoietin" BMJ (1964)