Red Blood Cell production

[MorningMist]

As b12 injections increase the no of red cells does anyone know what regulates this?

[palmier]

I think its because B12 deficiency slows down DNA replication in the precursors of the red blood cells. A b12-containing enzyme, Methionine synthase, converts one form of folate to another needed for the formation of a DNA component, thymidine. Too little b12 means precursors of red blood cells become too slow to divide, and in the process they grow too large, which may cause macrocytic anemia.

[MorningMist in reply to palmier]

thank you for explaining that process clearly 🙂

[FlipperTD]

Scientist, not medic.

Palmier's response is excellent, and explains macrocytosis in B12 deficiency. When DNA synthesis is restored, smaller [normocytic] red cells are produced. If there's a shortage of iron, even smaller [microcytic] red cells are produced.

If there's been anaemia, then as the Hb rises, the red count rises, and as the red cells are now normal-sized there will be even more of them. Once the Hb gets back to normal, the body detects this from the oxygen being carried, and this happens in the kidney.

When oxygen carrying is reduced, the kidney attempts to rectify this by increasing the secretion of Erythropoietin. This hormone is involved in the increased production of red cells, and until such point as the Hb approaches normal, Erythropoietin secretion falls once more. It's what's known as a 'feedback loop'.

I hope this isn't too confusing!

[MorningMist in reply to FlipperTD]

Thanks for the clear explanation Flipper. I had read about the role of erythropoietin but didn’t know that its production was affected by haemoglobin levels. I was wondering if raised b12 levels could possibly cause an abnormal no of red cells, that would be detectable in a blood count! Of course it makes perfect sense that the body regulates all of this.

So if you experience increased energy with injections does it indicate that your haemoglobin level was not optimal beforehand? I experienced an increase in energy but apart from low b12 my blood tests have been normal. No indication of anaemia.

[EllaNore in reply to MorningMist]

Good morning morningmist,

I don't know if this has anything to do with your situation. But my blood tests are borderline anemic and my doctor's refuse to see it. In fact I was borderline macrocytic anemic and they admit that yes my numbers are saying that, but it's not that bad. So they leave me with it and do nothing for me. However, I had further testing done, as I Huff and puff all the time and have extreme fatigue in my muscles, legs, arms, everything. So I asked for more tests not knowing what they would run, but evidently this particular doctor heard me and ran the proper tests, and finally, I have some answers. I have vasculitis and possible multiple myeloma, which has given me answers to some of my unexplained B12 conditions. Not everything is B12 related. I was blaming everything on that, but people with one autoimmune issue oftentimes have multiple autoimmune issues. There are other underlying situations that go on that without digging deeper into other blood tests, get completely ignored and overlooked. My ANA and my ANCA and a bunch of other blood tests were run and that's where I found my answers. You may think about having more blood test ran. You do not have to show signs of anemia to have pernicious anemia. And even when you do show signs, if it's not a high or low enough amount the doctors tend to ignore it. So you have to stay diligent and stick up for yourself and insist that other things should be tested.

My doctor recently took 21 vials of blood and ran some 30 odd tests. It was very productive. This doctor found things nobody else looked for. Some of the things that I thought were not going to be reversible may be with treatment for these other conditions. My fatigue and muscle weakness brain fog and things like that were not all because of B12, they were because I am not getting enough oxygen in my blood due to swollen blood vessels, arteries, etc.

But that does not come out in just any test. I don't know which test they ran on me that exposed this. I believe one was the PANCA and the ANA. Anyway I'm finding out that muscle weakness and fatigue is not always from B12. So I kind of feel like I have a deeply hidden anemia. I have no answers yet because the doctors haven't told me much. Still waiting on more tests and appointments. They've only verified vasculitis and possible multiple myeloma, they've ruled out sjogren's. But everything is still up in the air. But I thought possibly this information could help you or somebody else. One autoimmune disease often leads to others. Good luck.

[MorningMist in reply to EllaNore]

I am really glad for you that you’ve found a conscientious doctor and might get some long term answers to your symptoms. Accessing good healthcare is such a lottery. Hang on to that doctor!

My daughter was tested for similar things when she was was suspected of b12 deficiency - ana/ama/igG etc.

Aside from my (initial) b12 level all my tests results are always pretty much mid range and I think that I have some metabolism issue. Nothing that would interest any doctor I have met, but enough to seriously affect quality of life.

I’m sure it’s b12 related as I felt that a switch had been flipped within hours of my first injection. But I do keep my mind open to other causes.

Hope you get the treatment you need and deserve.

[EllaNore in reply to MorningMist]

Thanks for replying morningmist, Yes those are the tests that I took some of them. I hope your daughters came out negative.

After digging deeper into these new diagnosis, I found that people with pernicious anemia are very likely to have vasculitis and even multiple myeloma. At first I thought they were not linked. But I found that there's definitely a link between them.

So if your daughter has B12 deficiency and was tested for those things even though her test came back okay you might consider keeping an eye on that.

I don't know what that could be that would give you a reaction right away. I sure hope you find what it was or what it is. I have heard other people say they had/have instant responses. But not too many.

I hope I can keep this specialist. That doesn't always work out. A good doctor is hard to find. I wish you the best and good luck in finding what's causing your issues. And good luck to your daughter.

[Rexz]

Hi MorningMist, OK here's my attempt as it's a very complex process and the nitty details of what controls red blood cell production is somewhat of a mystery by the medical community and is just now being understood. When I was doing research on B12 and Megaloblastic Anemia I found that Red blood cells (RBC) are produced in the bone marrow under the control of the hormone erythropoietin (EPO). This Hormone is produced in the Kidney.

When human red blood cells are near maturity in the bone marrow, they divide in a way that is unique to only red blood cells. One half of the cell contains all the DNA and the other half contains the nucleus. The half with the nucleus is destroyed by your immune system and the half with the DNA will mature and enter the blood stream.

As the blood cell matures some very key components are B12, Folate, Iron. I was interested in B12 of course and proper B12 and Folate are required within the RBC DNA for proper synthesis and RBC formation into a healthy cell to eventually enter the blood stream. When B12 is deficient, as in those with PA, then faulty DNA synthesis occurs causing the RBC to become enlarge and deformed still within the bone marrow as they mature.

When they do become mature, they will attempt to enter the blood stream where many are just too large to escape the bone marrow. They will spend their entire lives stuck in the marrow. Then there are those large and deformed RBCs that are still small enough enter the blood stream.

So you end up with too few RBCs or anemia and the enlarged deformed lack the ability to carry enough oxygen. This is referred to as Megaloblastic Anemia.

So the control to produce a RBCs comes from the kidney produced hormone EPO but once the red blood cell is created yet still immature the instructions to grow and mature are controlled by its internal DNA synthesis. B12 is required proper DNA synthesis, without proper B12 the RBC DNA will issue faulty instructions to the cell for growth. Thus injecting or supplementing B12 will correct this issue.

I think I have that right anyway! LOL I ain’t no doctor, and yes, I know ain’t, ain’t a proper word. 😆

Hope this is helpful, Rexz

[FlipperTD in reply to Rexz]

Scientist, not medic.

Nicely put, and pretty good, Rexz. and ain't might not be a proper word but it works for me, The macrocytes are still quite effective at oxygen transport, there just isn't enough red cell mass overall to cope with the requirements. But macrocytes work just as well; they can get to all the places that normocytes can. Keep it up!

[Rexz in reply to FlipperTD]

Thank you FlipperTD. Great clarification...so much to learn.

[EllaNore in reply to Rexz]

Excellent information RexZ.

[MorningMist in reply to Rexz]

Thank you, very interesting to have the whole process explained clearly.