With macrocytic, what are we looking for?
Lab findings, decreased hemoglobin.
Increased MCV, greater than 100.
Now, pay attention here because
we will now differentiate between
folate and B12 deficiency.
If it’s folate,
you will have increased homocysteinemia
and hyperhomocysteinuria, but
you do not find what here?
Good, you don’t find
decreased serum B12 and what have I added
here that folate deficiency doesn’t have?
You see that?
And do you remember what biochemical
pathway dealt with methylmalonic aciduria?
That’s your myelination
pathway, wasn’t it?
And what is that enzyme that
B12 was a co-factor there?
methylmalonic mutase, right?
And then if it was homocysteine, you’re
dealing with methionine synthase.
A lot of M’s there for B12.
Signs and symptoms of
anemia with macrocytic.
Now under B12, I’m going
to first walk you through
those neurologic symptoms that
I was referring to earlier.
When I was referring to our
ataxic gait, spinocerebellar.
If it’s proprioception
and positive Romberg,
that will be posterior
column or dorsal column.
And lateral corticospinal tract will
then give you positive Babinski sign
referring to your upper
motor neuron lesion.
You’re taking a tongue depressor
and in an adult, you take the lateral
aspect of the foot and you caress it.
And as you do so,
as an adult normally, we should
then flex our toes, okay?
However, if it’s positive
Babinski in an adult
where the toes then fan out upon
lateral caressing of the toe --
Or excuse me, lateral
caressing of the foot.
And then this is going to be a
sign of upper motor neuron lesion.
And this is not good, this is not good.
Last little thing that I wish to add
in here and just stick with me,
the physiology aspects of
treatment of B12 deficiency.
The boards love asking
questions like this
so that they know that you know that
you have an understanding of B12.
Earlier, I said that if you find
a substance within your urine
upon consumption of it or that
food or whatever it may be,
then you know that it had to
have been reabsorbed first,
and gotten into urine.
Let me walk you through the following.
Let’s say your patient has all the
signs and symptoms of B12 deficiency,
anemia and, unfortunately,
there is neurologic deficit
that is occurring.
And that neurologic deficit is
going to be irreversible.
Now, you don’t find any B12 in the urine
because whatever that the patient
is not consuming, let’s say now,
there is dietary deficiency either in a
nursing home with an elderly patient
or maybe, maybe it’s a vegan
that we talked about for years.
Well now, at this point,
there is consumption
of it and there is
supplementation of B12,
and there is no problem inside
your body, just lack of diet, right?
So therefore, after consuming
it, you can then expect
to find B12 in your urine because then
it has been reabsorbed and filtered
and taken up to the
liver and so forth.
Keep that in mind.
Now understand though,
in a true Schilling test,
you will then have to saturate all
the receptors in the liver for B12
and that will not be asked
because that’s radio-labeled.
But the concept here
well, if your patient had B12
deficiency and now at this point,
you’re suspecting that there is
something like pernicious anemia.
Well, let’s say that you
give intrinsic factor
and now you find that
there reabsorption of B12
from the terminal ileum into the
plasma and it has been filtered.
But let’s say that you
give intrinsic factor
and you still do not find
the B12 in the urine.
Your diagnosis cannot
be pernicious anemia.
So what’s your next step?
You need to find out where this
B12 deficiency is occurring.
The diet doesn’t help, the supplementation,
intrinsic factor didn’t help.
Let’s go ahead and give this
patient a pancreatic enzyme.
Would you tell me physiologically why
you required a pancreatic enzyme?
To remove the R-factor from your B12
so that it then gets properly reabsorbed in
the terminal ileum with intrinsic factor.
So now, you give pancreatic enzyme
and you find B12 in the
urine, what’s your diagnosis?
So now, let’s say the diet didn’t
work with supplementation.
The intrinsic factor didn’t work.
How do you know?
Because you ended up finding B12 in
the stool and it wasn’t in the urine.
And in pancreatic enzyme, you had
given it and that didn't work.
Next maybe, you
You have antibiotics and
you find B12 in the urine.
Theoretically, what happens here?
Well, your diagnosis should be?
Good, bacterial overgrowth, right?
So bacterial overgrowth there, you kill
off the overgrowth with antibiotics.
The B12 is now properly reabsorbed
and it ends up in the urine.
Do you understand the concept of how
there are certain attributes of the
Schilling test that you’re going to use
from head to toe so that you can
then properly diagnose your patient.
And how they will most
likely wear this with B12
is going to be the fact that
you have cobalamin, okay?
Keep that in mind.
And whether or not you find that in urine
and that table that I showed you with B12,
all the different methods by which
you can develop it is important.
Last little thing that I wish
to bring to your attention,
is it megaloblastic anemia
that you only find?
Meaning megaloblastic RBCs.
Remember that the
neutrophils also are not
properly developing because
this is pancytopenia,
you would expect to find --
Well, can you think of what a normal
neutrophil should look like?
Should they be segmented?
But what if you end up
finding 8-12 segments?
That’s called a
And that to you should clue you in,
Oh! I must be suffering from --
or your patient is suffering
from megaloblastic anemia.
Last little bit that I wish to
bring to your attention is,
earlier when I set up the
overview for anemias,
I said there was megaloblastic
and non-megaloblastic anemia.
Up until this point, your focus should
be strictly upon megaloblastic anemia.
And where is my problem
with megaloblastic anemia?
It’s a fact that DNA
or in the bone marrow,
you don’t have
Maybe either due to lack of DNA synthesis
or as you saw with Diamond Blackfan anemia,
we have a problem with
erythroid progenitor, right?
If it’s non-megaloblastic
then you‘re thinking about alcohol,
liver disease, or reticulocytosis.
Think about those.
Liver has nothing to do
with the bone marrow.
Alcoholism has nothing to
do with the bone marrow.
And reticulocytosis means the
bone marrow is producing
too many reticulocyte which is
immature RBC into circulation.
Would you tell me the size of a
cell that is always a little bit
immature or premature than
the mature cell, the size?
The size is always bigger.
So reticulocyte's always
larger than an RBC.
And so therefore, you can have
non-megaloblastic macrocytic anemia.
The big ones here, liver disease,
alcoholism and reticulocytosis.
Keep those in mind and that gives
you big time high yield information
for all macrocytic anemias that you have
to be familiar with on your boards.