Why do we need red blood cells?

Question

From what I know, the main function of red blood cells (RBCs) is hemoglobin transport. So, why do we need cells packed with hemoglobin: why can't it travel freely in the bloodstream?

My own thoughts were:

1) Having hemoglobin packed into cells means it can be released where it's most needed. For example, when we are exercising, our muscles need more oxygen, so more erythrocytes release their oxygen in the muscle tissue.

2) The diameter of a capillary is much bigger than a single protein molecule's diameter, but comparable to a cell's diameter. So, when cells are traveling through a capillary, all of them are close to its walls. However, when free molecules are traveling through it, some of them are close to the walls, while the others are in the "middle". I figured, those in the "middle" can't exchange oxygen with the surrounding tissues. So, red blood cells make gas exchange more effective.

Do you think any of this makes sense? Why in reality do RBCs exist?

Any insight or book recommendations would be very appreciated:)

Answer 1

Hemoglobin molecules used to manufacture these products are not contained by a red cell membrane, and when released into the vasculature, these molecules rapidly scavenge nitric oxide.This can result in systemic vasoconstriction, decreased blood flow, increased release of proinflammatory mediators and potent vasoconstrictors, and a loss of platelet inactivation,17- 20 creating conditions that may lead to vascular thrombosis of the heart or other organs. This mechanism has recently been shown in preclinical models to be responsible for injury during hemolytic states, in which hemoglobin is also released into the circulation.21

Unlike naturally occurring hemoglobin, manufactured cell-free hemoglobin-based blood substitutes (HBBSs) can be chemically altered to theoretically minimize such toxicities. It has been postulated that cross-linking, polymerization, or pegylation of hemoglobin will create larger, more stable HBBS molecules, preventing extravasation and thereby leading to a reduction in toxicities related to nitric oxide scavenging. At least 1 manufacturer has also chemically increased the affinity of its HBBS for oxygen (lower P50, the partial pressure of oxygen required for 50% hemoglobin saturation) to decrease arteriole oxygen transfer and thereby potentially eliminate untoward cardiovascular effects.

• 2008 - Cell-Free Hemoglobin-Based Blood Substitutes and Risk of Myocardial Infarction and Death

So cell free hemoglobin is toxic. As you can see this toxicity can be reduced in other ways too, so it seems like there is an evolutionary pressure in the direction of having blood cells, maybe it is simpler this way. To answer the other question, I think there can be free HGB in the blood when blood cells fall apart because of an infection e.g. malaria, etc...

Hemolysis in falciparum malaria results in NO quenching by cell-free hemoglobin, and may exacerbate endothelial dysfunction, adhesion receptor expression and impaired tissue perfusion. Treatments that increase NO bioavailability may have potential as adjunctive therapies in SM

• 2008 - Relationship of Cell-Free Hemoglobin to Impaired Endothelial Nitric Oxide Bioavailability and Perfusion in Severe Falciparum Malaria

Btw. I agree with rhill45, I think too that it is easier to regulate O2 and CO2 exchange if you have a specialized cell type, so it might have regulation purposes. It can have recycling purposes either, because it is hard to distinguish between old (damaged) and new HGB when they are in a cell-free form. This problem probably can be solved by destroying only glycosylated hemoglobin, but I guess it is much easier to filter out the old RBCs in the spleen...

In the process of maturation, a basophilic pronormoblast is converted from a cell with a large nucleus and a volume of 900 fL to an enucleated disc with a volume of 95 fL. By the reticulocyte stage, the cell has extruded its nucleus, but is still capable of producing hemoglobin.

• according to wikipedia (without citation).

Other sources claim the same, with the extension that this period lasts only for a short time, because the cell soon loses its mRNA and so it stops producing HGB. So according to these articles RBCs create the HGBs in the early stages of their life. (I did not find a real scientific article about this, but I can accept this theory.)

According to Chris this toxicity is just a protection mechanism, so I dug deeper.

Bacterial virulence is greatly enhanced by freely available iron, such as that in fully-saturated transferrin or free haemoglobin. Following trauma a fall in tissue Eh and pH due to ischaemia, plus the reducing powers of bacteria, can make iron in transferrin freely available and abolish the bactericidal properties of tissue fluids with disastrous results for the host. Hyperbaric oxygen is a possible therapeutic measure that could restore normal bactericidal systems in infected tissues by raising the Eh and pH.

• 2006 - Iron and infection: the heart of the matter

Iron lies at the center of a battle for nutritional resource between higher organisms and their microbial pathogens. The iron status of the human host affects the pathogenicity of numerous infections including malaria, HIV-1, and tuberculosis.

• 2012 - Hepcidin and the Iron-Infection Axis

So RBCs protect the iron against microbial pathogens, that's their key role. I think every other related problem, like O2 release regulation, free HGB toxicity, HGB recycling, etc... can be solved with free HGB as well, so most probably iron protection is the evolutionary pressure to store HGB in blood cells instead of letting it be in the blood in a cell free form. It's funny that every single book gets this wrong, and they claim that carrying oxygen is the most important role of this cell type, while they aren't mention anything about iron protection... :-)

Answer 2

This is a well worded question. There are more reasons than the following but the most apparent is hemoglobin production and its transport. The erythrocyte is a cell whose structure is optimal for its function-the production and transport of hemoglobin.

It lacks a nucleus and organelles so that it can devote almost 100% of its energy to hemoglobin production. It has this bi-concave disk shape to increase its surface area thus increasing the exposure of hemoglobin to oxygen and CO2.

It's a small and flexible cell allowing them to easily maneuver the capillaries (where they work).

Because it's anuclear it has a short lifespan but they are rapidly produced and regulated by erythropoietin.

In order for tissues to receive oxygen and rid themselves of carbon dioxide there needs to be an orderly transfer and movement of hemoglobin from the tissues to the lungs and back-and-forth. Without this cycling of hemoglobin on the erythrocyte the protein would move more in the body through diffusive means. This would not promote the required segregation of oxyhemoglobin in the tissues and carbaminohemaglobin in the lungs.

Check out any edition of Anatomy and Physiology by Marieb. All editions have an entire chapter related to the subject

Answer 3

This is not an answer to the question, but tangent comments that might be useful for how you look at the problem (and too long for a comment). First, for a question like this it is useful to look at other solutions to the same problem. For instance, the second most common molecule for oxygen transport is Hemocyanin, and this is not bound to cells but is directly suspended in hemolymph (arthropod/mollusc "blood"). So specialized cell types for oxygen transport is not a necessity for effecient oxygen transport in rather advanced organsism. So your question; "why do we need cells packed with hemoglobin: why can't it travel freely in the bloodstream?", while being true for humans and other vertebrates, is not true for oxygen transport in all "complex" animals.

Second, while there seems to be good reasons for why hemoglobin is bound in RBC, you should at least entertain the idea that the cause of RBC-bound hemoglobin in vertebrates is an evolutionary contingency (i.e. a random historical event). Evolution is always constrained by previous evolutionary history, and the reason that all vertebrates (+ a number of other organsisms) share RBC-bound hemoglobin may simply be that they share a common ancestor. This does not mean that it lacks advantages, but it also means that it might be misleading to search for the reason for RBC-bound hemoglobin in a particular species. For some background on evolutionary contingencies and many useful references in the intro, as well as an interesting experiment to test for contingencies, you can have a look at Blount et al. (2008) (part of Lenski's Long-term Experimental Evolution project).

Answer 4

I remember going to a chemistry lecture which mentioned this (the lecture was on blood transfusion in general).

The main reasons are:

1) Hemoglobin is toxic to the human body: Hb in RBCs is a tetramer, but in the plasma it breaks into two dimers --> toxicity in the kidneys. Hb needs modification by cross-linking or recombination. Wikipedia states that this is Acute Tubular Necrosis.

2) Hb in plamsa decreases osmotic pressure

3) Hemoglobin removes the NO from the vessel walls causing vasoconstriction, shrinkage of the vessels. --> this was the main focus of the chemistry lecture; there was a lot of talk about free radicals and stuff but I've unfortunately forgotten the details

I've also searched a bit on the web and some people (one yahoo answers) confirm rhill45's answer.

I think searching failed blood transfusion products (people have tried transfusing Hb directly) will be of great help.