Dealing with Megaloblastic Anemia
in Health ·
Pernicious anemia basically kicks off when the body’s internal security system—its autotolerance mechanisms meant to protect our own tissues, cells, and biomolecules—just stops doing its job. When the immune system bumps into its own antigens, things usually go one of three ways (hopefully the good kind):
1. Apoptosis, which is just fancy talk for programmed cell death
2. Anergy, where the cells basically go into a functional coma
3. The creation of autoregulatory cells
In those three scenarios, there's no "second signal" to tell the system that this contact is actually a threat. But when autotolerance fails, that second signal can suddenly be provided. It's been documented that microorganisms can actually trigger the expression of costimulators. Basically, a microbe can mimic an autoantigen and simultaneously kickstart that costimulator expression, providing both signals needed to launch an attack.
Think of pernicious anemia as a case of the immune system being way too sensitive—it's an overkill response. We're talking Type II hypersensitivity here, meaning it's driven by autoantibodies. These antibodies go after the parietal cells and/or the intrinsic factor tucked away in the stomach lining:
Those parietal cells are responsible for pumping out the intrinsic factor, which is absolutely vital for absorbing Vitamin B12 down in the terminal ileum.
What you'll see in the lab work:
A massive drop in red blood cell mass, megaloblastosis, megalocytosis, hyperchromia, poikilocytosis, along with leukopenia and some moderate thrombocytopenia.
The specific markers: Vitamin B12 excretion stays totally normal during the first stage of a Schilling test, only showing up in the second stage once you add back the intrinsic factor; low serum B12 levels; elevated methylmalonic acid in the urine; and high serum LDH-1 levels, which happens because the body is frantically breaking down megaloblasts loaded with lactate dehydrogenase in the bone marrow (what doctors call ineffective erythropoiesis). You also see a positive response to parenteral B12 therapy, which typically triggers a huge reticulocyte crisis around day eight (that's our first follow-up) after starting 2g of B12 daily; a complete lack of HCl in gastric juice even after histamine stimulation; and finally, high titers of antibodies against intrinsic factor and parietal cells. Usually, you'll hit full remission between weeks five and eight of therapeutic B12 dosing (our second follow-up).
1. Apoptosis, which is just fancy talk for programmed cell death
2. Anergy, where the cells basically go into a functional coma
3. The creation of autoregulatory cells
In those three scenarios, there's no "second signal" to tell the system that this contact is actually a threat. But when autotolerance fails, that second signal can suddenly be provided. It's been documented that microorganisms can actually trigger the expression of costimulators. Basically, a microbe can mimic an autoantigen and simultaneously kickstart that costimulator expression, providing both signals needed to launch an attack.
Think of pernicious anemia as a case of the immune system being way too sensitive—it's an overkill response. We're talking Type II hypersensitivity here, meaning it's driven by autoantibodies. These antibodies go after the parietal cells and/or the intrinsic factor tucked away in the stomach lining:
Those parietal cells are responsible for pumping out the intrinsic factor, which is absolutely vital for absorbing Vitamin B12 down in the terminal ileum.
What you'll see in the lab work:
A massive drop in red blood cell mass, megaloblastosis, megalocytosis, hyperchromia, poikilocytosis, along with leukopenia and some moderate thrombocytopenia.
The specific markers: Vitamin B12 excretion stays totally normal during the first stage of a Schilling test, only showing up in the second stage once you add back the intrinsic factor; low serum B12 levels; elevated methylmalonic acid in the urine; and high serum LDH-1 levels, which happens because the body is frantically breaking down megaloblasts loaded with lactate dehydrogenase in the bone marrow (what doctors call ineffective erythropoiesis). You also see a positive response to parenteral B12 therapy, which typically triggers a huge reticulocyte crisis around day eight (that's our first follow-up) after starting 2g of B12 daily; a complete lack of HCl in gastric juice even after histamine stimulation; and finally, high titers of antibodies against intrinsic factor and parietal cells. Usually, you'll hit full remission between weeks five and eight of therapeutic B12 dosing (our second follow-up).