Regulation of Erythropoiesis & Removal of RBC

Regulation of Erythropoiesis & Removal of RBC

Erythrokinetics

1% of erythrocytes, aka, red blood cells, are removed and replaced every day.

The production of new red blood cells, called erythropoiesis, occurs in the red marrow of spongy bone.

Regulated by hypoxia, sensed by kidney.

On average, erythrocytes travel in the circulatory system for approximately 120 days; recall that they are responsible for oxygen and carbon dioxide transport.

Once they are no longer viable, splenic macrophages remove RBCs via phagocytosis.

Regulation of Erythropoiesis

Regulation:

Tissue oxygen level, aka, hypoxia, regulates erythropoiesis via negative feedback.

When the kidney senses hypoxia, hypoxia-inducible factor 1 (HIF-1) activates the gene to increase erythropoietin (EPO) synthesis (EPO is also synthesized by other organs, including the liver, but in quantities insufficient to maintain homeostatic erythropoiesis).

In the red marrow of spongy bone, erythropoietin stimulates erythrocyte formation.

Consequently, oxygen delivery to the tissues increases to homeostatic levels (aka, normoxia), which, in turn, downregulates erythropoietin synthesis.

EPO production is also initiated by testosterone and thyroid hormones.

Key characteristics of healthy mature red blood cells

Biconcave center is referred to as the "central pallor," this is region is relatively thin, and, therefore, appears lighter in color.

Cell membrane is deformable, which allows passage through small spaces, and is permeable to gases and ions.

The cytoplasm of the erythrocyte contains abundant hemoglobin, which binds iron and maintains fluid osmolarity.

Healthy mature erythrocytes lack nuclei, mitochondria, and endoplasmic reticulum.

Cytoskeleton proteins interact with the cell membrane to allow deformation.

Cytoplasmic enzymes maintain the cell membrane and keep iron in its ferrous form.

Degradation of Erythrocytes

Because erythrocytes are lacking in protein-synthesizing organelles, they cannot replace these enzymes as they are used; hence, the limited supply of cytoplasmic enzymes determines the red blood cell lifespan.

As they mature, erythrocyte cell membranes degrade and loose pliability; these malformed cells present a hazard, as they can block blood flow through the vessels and/or provide insufficient gas transport to the tissues.

Removal

Some red blood cells will rupture within the blood vessels (aka, intravascular hemolysis), but most aging cells are removed and destroyed within the spleen (extravascular hemolysis).

Spleen removes malformed cells via two mechanisms:

The so-called splenic sieve mechanism traps rigid, unpliable cells in capillaries; cells burst, release contents that macrophage will phagocytose.
Splenic macrophages detect senescent cells, engulf in phagosome.

In both cases, red blood cell contents are released in splenic macrophage, and hemoglobin is dismantled:

Heme oxgenase, a macrophage enzyme, releases iron from hemoglobin; iron is then stored as ferritin and/or hemosiderin or it binds to transferrin for transport to the red bone marrow to be re-used in hemoglobin synthesis.

Porphyrin portion of hemoglobin is converted to bilirubin, which is later excreted in bile by the liver.

Globin, a protein substance, is broken into its amino acid components and added to the amino acid pool.

Regulation of Erythropoiesis & Removal of RBC

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