Over time, old medical terms (such as Alzheimer's dementia) take on a new meaning as research makes new findings. I wonder about Pernicious Anaemia as I can never be sure if a web page or article is using an out of date meaning or not.
Speaking as rigorously as possible ... am I right in thinking that Pernicious Anaemia is nowadays seems as a subtype of Macrocytic Anaemia (characterised by large but inefficient red blood cells) which is due to B12 deficiency and commonly caused by poor gut absorption of B12?
If so then presumably Pernicious Anaemia can also be caused by other problems of B12 absorption or utilisation, such as defective genes? Would this still be called Pernicious Anemia?
What if a patient has poor B12 absorption to the point of general deficiency but does NOT have any significant form of anaemia? Would this nowadays get classified as Pernicious Anaemia?
I ask all the above because I don't seem to have B12 absorption problems and am unsure if I do or do not have anaemia. (At times I get exceedingly breathless on the slightest exertion and this lasts for ages.) I do benefit from B12 injections and can relate to all the non-blood symptoms. I also seem to need to top up my B12 very regularly or I will relapse quite quickly.
Thanks for any explanatory comments.
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I’m no expert but I’ve come to think of PA as any form of genetic or inherited condition that leads to B12D. This would include any autoimmune reaction to parietal cells in the stomach or to intrinsic factor itself. PA tends to manifest in childhood and is for life.
Macro cystic anemia is a symptom of B12D and one of the blood test results that Drs use to diagnose a vitamin B12 deficiency. I happen to have had stomach surgery that after 17 years and multiple misdiagnosis was finally diagnosed as macro cystic anemia. There is no special name like “Acquire B12D”
The third category is vegetarian or vegan diets that in some cases are religious or in other cases are fad diets and precautions of supplementing with B12 are either not known or not taught or just ignored can lead to a B12D.
It is the B12D and folic acid deficiency that causes the nerve damage that no one recovered from pre-1920s that gave the condition the name “pernicious” or deadly anemia. They became schizophrenic and were put into mental asylums to eventually die.
The overarching condition is the B12D with no special name.
Other anemias, like iron deficiency, don’t cause nerve damage and can be recovered from with iron supplements.
Pernicious anaemia is an autoimmune disease. If you have PA then the immune system attacks the cells in the stomach that produce something called Intrinsic Factor. This is essential for getting the B12 molecule from the gut to the blood. Without it, people with PA cannot absorb B12.
PA is one possible cause of a B12 deficiency, where there is not enough B12 in the blood. There are many other causes, but they can be divided into two classes - absorption problems and dietary insufficiency.
Absorption problems can be caused by many things that affect the gut - infection with H. pylori, gut surgery, drugs like PPIs and metformin, etc.
A dietary insufficiency is when the person does not eat enough B12 in their diet. It is common in vegetarians (25% of them) and vegans (75% of them) who do not take B12 supplements.
There is also a functional B12 deficiency. This is when there's lots of B12 in the blood, but it doesn't get into the right places in the cells. Not common. A blood test for two compounds used up in reactions mediated by B12 - MMA and hCys - can indicate a functional deficiency if their levels are raised while B12 and folate levels are sufficient.
A B12 deficiency can cause a problem with the development of red blood cells. This results in red cells that are larger than normal. This is called macrocytic anaemia. It can also be caused by a folate (Vitamin B9) deficiency.
tl/dr:
Some people with a B12 deficiency have it caused by Pernicious Anaemia.
Some people with a B12 deficiency have macrocytic anaemia
Not everybody with Pernicious Anaemia has macrocytic anaemia and vice versa.
fbirder I think I see where I was getting mixed up. You write "Not everybody with Pernicious Anaemia has macrocytic anaemia" whereas I was thinking Pernicious Anaemia, by definition, had to include symptoms of anaemia.
No, the myelin sheath damage is independent of the red cell problem. Although both have the same underlying cause - the fact that DNA cannot be made properly without adequate supplies of B12 and folate.
fbirder Do you know where in the pathways the red cell damage occurs?
I have seem one account say red cell formation depends on "thymidylate" in the folate cycle -- but others suggest red cell problesm come from methylation problems in the homocysteine-methioinine cycle.
The problem with red cell formation is the inability to produce the large amounts of DNA quickly enough. As the cells that will, eventually, become red blood cells they repeatedly divide. This cell division requires doubling the amount of DNA at each step. If the cells can't make enough DNA then they continue to grow, rather than divide. So you end up with larger red cells than normal.
Deoxythymidine is one of the four bases that make up DNA. It requires methylenetetrahydrofolate for its production. Two other DNA bases, adenine and guanine, require formyltetrahydrofolate. So folate is obviously important for DNA synthesis.
If you have a severe deficiency of B12 then the body isn't easily able to convert methyltetrahydrofolate into tetrahydrofolate (from which methylenetetrahydrofolate and formyltetrahydrofolate are produced). This 'folate trap' affects the production of those three DNA bases.
A B12 deficiency also reduced the production of methionine which, via S-adenosylmethionine, is important for methylation of DNA, which is one of the body's major methods of switching genes on and off.
fbirder Thank you so much for explaining the red blood cell DNA connection. I have been puzzling over this for a long time and you explanation helps a lot.
I think your diagram shows that taking methylfolate (Metafolin, etc) will do nothing to help DNA synthesis because it enters the folate cycle at a point which does not feed back to creating those compunds necessary for DNA creation. I get terrible breathlessness, perhaps a sign of increasing anaemia, when I take methylfolate instead of folic acid.
By the way, does poor DNA methylation (via the s-adenosylmethionine you mention) also contribute to macrocytic blood cells or is it all happening in the folate cycle?
PS: I love the picture of a goldfinch on your web site which I found from your link. It's my favourite bird.
as fbirder says, macrocytic anaemia is a possible symptom of B12 deficiency whether it is caused by PA or not - however something like 25% of people don't actually present with macrocytic anaemia. More importantly sorting out macrocytic anaemia won't resolve all the symptoms of PA or B12 deficiency. B12 is used by a number of processes that go on in your cells. The process that produces healthy red blood cells is just one of them - other processes have other consequences and it really does appear that people develop symptoms in very individual ways.
My understanding is that PA is a specific auto-immune disorder that leads to B12 absorption problems. It is frequently associated with other auto-immune disorders, such as hashimotos (autoimmune thyroidosis).
There is no known reason why but many people do actually seem to need much higher B12 levels post loading doses and symptoms can return long before levels actually fall back into the 'normal' range used to diagnose absorption problems.
Gambit62 You write: "As fbirder says, macrocytic anaemia is a possible symptom of B12 deficiency whether it is caused by PA or not."
The way you use "PA" suggests you see PA defined as the cause rather than the outcome. I was seeing it the other way around: I was thinking PA is a description of the outcome symptoms (macrocytic anaemic, etc) rather than a particular cause.
Fbirder does the same as you and sees PA as the cause when he writes "Some people with a B12 deficiency have it caused by Pernicious Anaemia".
I was blown away when my Dr first told me: "You have Macrocytic Anemia, B12 deficiency, Folate deficiency & PA" when I asked what it all meant, he just said I'd need injections for the rest of my life. No explanation or anything.
I've never been vegetarian or vegan & have always eaten meat & dairy products all my life.
Many years ago I was told by my then Dr I possibly had IBS but was never treated for it after an endoscopy didn't really show anything up. The symptoms vanished after a while.
Around 2007 my Dr prescribed me OxyContin due to my back. It wasn't until I found out what this drug was & how it was making me feel that I started to research it. Thankfully, I was very lucky & have been off this drug a few years now. But what I found after reading books & doing research on opiates etc, was that most Heroin addicts have a severe B12 deficiency & don't even know it.
The years I was on a very high dose of firstly Oxycodone & then OxyContin, I now know is what caused my PA etc.
It's a long learning curve that I'm on but the great people on here have taught me loads more than my Dr ever told me about any of it.
I'd never even heard of any of PA before being diagnosed last year.
Problem with being a long-term vegetarian is that after loading doses, B12 injections every 8 weeks should sort that out fairly quickly I would have thought. But what if it doesn't ?
Presumably, at least some vegetarians have also got Pernicious Anaemia. Or some other problem. My GP told me Functional B12 deficiency, when B12 was at >2000 nmol/L after injections, but still symptomatic and MMA raised (always 350- 400nmol/L). "Patchy gastric metaplasia" in gastroscopy report; Coeliac disease ruled out but nothing ruled in.
What if you changed your diet to include more eggs, more cheese, more fortified cereal, more fortified milk, supplemented folate and ferritin etc. daily and injected B12 every other day, and still had symptoms every day over a year later ?
Well, it could be something else. But a lot of "something elses " were ruled out a long time ago. Like you, IBS was talked about many years ago...but that is a group of symptoms and not a diagnosis. Also have had psoriasis in the past.
Some of my symptoms have gone. Some have changed for better ones: I don't need a 2 or 3 hr nap in the afternoons now, but I do have air-hunger every day.
What else to do ?
Think I'm already doing all I can, and hoping I don't get stuck like this.
Trying not to pin all of my hopes on the new research that PAS is carrying out (as it might take years and years, and benefits could eventually be restricted to people with a PA diagnosis) and my upcoming and final appointment with Inherited Metabolics Diseases consultant (which could prove as disappointing as my other appointments have been). Hoping DNA might tell a story that other consultants have missed.
I remember being told that I would need to arrange appointments with the nurse because I had B12 deficiency, and that after having 6 injections in a month, was told that it would be my responsibility now to book regular injections (at that time, every 3 months) and that this would be for life. But that was in February 2016.
No-one has yet even asked me what I eat/ don't eat that might have caused B12 deficiency, low-range folate and ferritin and osteoporosis of the spine. Luckily, what I eat/don't eat seems to make very little difference to symptoms, which would indicate that being a vegetarian is not the main problem. I was after all a strong, healthy one for 35+ years before all this.
Frequent injections of B12 do make a difference, but extremely slowly, and not always !
My story is just unfinished and frustrating. Yours is absolutely horrifying, Ritchie1268 .
Sorry to hear you're still suffering with the air hunger issue. This was one of the very first symptoms I used to get, to go away & hasn't returned.
I was thinking about why my Dr didn't ask me about my diet & just said I'd need Injections for life.
Looking back now, after finding a note last night from 4 years ago where I would write down notes on how I felt while tapering the massive dose of opiates I was taking. My Dr did everything he possibly could when the agencies he sent me to to get the help to come off them kept turning me away. He was as frustrated & annoyed as I was & told me to write to my MP at the time. I had forgot all about this till I read my notes, and it wasn't down to "Brain Fog" it was down to the amount of opiates that just made everything at that time a blur.
I remember now that he probably just thought, as I do now, that it was indeed all the opiates that has caused where I am now with PA etc.
Something else I forgot, I was sent for a brain scan 2 years ago to check my pertuarty gland as my testosterone level was rock bottom. Now I know that Heroin actually "breaks" receptors in your brain.
I have now been off OxyContin over 3 years, the methadone they eventually put me on to stop withdrawals, I've been off around 6 months now.
Today, the only issues I have now are, what were just tingling feet & fingers, to painful feet, like walking on glass & pebbles after walking so far. Small fibre neuropathy the Neurologist thinks. I just hope regular SI will repair this nerve damage but, like you say, maybe very slowly or not at all!?
Still get stomach issues & need to look into different types of folic acid I think??
I know everyone who reads my posts will think, not again, he's ranting about OxyContin again 🙄 but after beating the hardest thing I've ever had to face & something that should have & very nearly killed me, it's final, kick was, "you may have beaten your addiction to me but, I'll leave you with this"
...and it seems immaterial in some ways whether or not Pernicious Anaemia is the reason because the "this" you mention above is the particular set of symptoms you get from your B12 deficiency.
My burning, stiff, sore feet now just tingle, especially in hot weather. I was very lucky there.
You're not ranting about OxyContin, you're working out how to get the best life you can. Where that includes, as in your case, an element of "giving back", you have my continued support and admiration. Keep going !
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