Speaker 1:

It's time for another warmup. Let's get going, which genetic syndrome is caused by each of the following
underlying mechanism. So first we have absence of the HG P RTA that's Lesh nine syndrome deficiency
of Al delays B. That's gonna be fructose intolerance, deficiency of CYS defining synthase. That's gonna be
homocystinuria goose one phosphate iReal transferase deficiency resulting in intellectual disability
hepatosplenomegaly and cataracts. That's gonna be glycemia. Next. We have deficiency of tyrosinase
that's gonna be a next question. What is Potter sequence? So this is where you have a bilateral renalis
because there is a malformation of the Ric bud that causes oligohydramnios because the fetus is not
making Uum and that causes a lot of problems as well. Like limb deformities, facial deformities, and
pulmonary hypoplasia all right, that's it for the warmup. Let's get to that lecture. Now

Speaker 2:
In this video, we're gonna discuss some basic concepts related to red blood cells. We've already talked
about the physiology of hemoglobin and the oxygen carrying capacity of red cells, but now we're talking
more about some terminology used to describe red cells and the various abnormal shapes that red cells
can take on in various these states. So the formal scientific sounding name for red cells is erythrocytes.
They're a nucleate. So they've lost their nucleus and they're by concaves so that they have a large
surface area which helped facilitate gas exchange. They're also very flexible, which is important because
they have to be able to squeeze through those narrow capillaries and the main molecule that's
responsible for the BI cavity. And the flexibility is a cytoskeletal protein called spectrum. So make sure
you're familiar with that name. So anytime you lose that classic BI concave shape, like with sickle cell
disease or with hereditary, cytosis, the blood becomes more viscus, which can lead to sludging in the
capillaries because the red blood cells are taking the wrong shape.

Speaker 2:
Now mentioned a few times already that red cells rely on glucose for their energy. Even in the fasting
state, your red cells still need glucose. 90% of that glucose is anaerobically metabolized to lactate, and
10% is metabolized by the HMP shunt. And we mentioned that if you have a deficiency of P eight kinase,
which is an enzyme in the glycolysis pathway, that's gonna cause a getting energy to the red blood cells
and the red cells will Heise. We'll see that again. When we talk about causes of hemolytic anemia, you
should also note that the average lifespan of a normal, healthy, mature red cells is about 120 days.
That's potentially testable. You also need to be familiar with the special vocabulary used to describe red
cells. So if a pathologist looks at a peripheral smear says there's anti ISO cytosis what does that mean?
Anti cytosis means you have red cells of varying sizes.

Speaker 2:
So ISO means same. So anti ISO cytosis means the cells are not all the same size, which is abnormal or
the pathologist might report that there's poco cytosis poco cytosis means you have cells of varying
shapes. We'll get to all those weird shapes in a second, if you have too many red cells that might be
called polycythemia, or it could be called erythrocytosis two terms for the same thing, and the immature
red cells are called meticulous sites. So when your bone marrow is busy, churning out new blood cells,
you're gonna see more and more of those immature forms on the smear. And that's called meticulous
cytosis, but here's some good news. You don't really need to worry about remembering all the different
stages of different red cell precursors. Let's talk about some more things that the lab might on a
peripheral blood smear, various types of pathological red cells.
Speaker 2:
So these are definitely high yield for you to know. And I'd be very surprised if you didn't have at least
one question on one of these, let's start with basilic stickling. These are little purple basilic dots all over
the cell, which are thought to be clumps of denatured RNA within the red cell, or possibly ribosomes
that clump together, the main disease state I want you to associate with basilic stickling is lead
poisoning. Now there are other things that might cause basilic sting, such as thalasemias anemia of
chronic disease, alcohol abuse, but I want to remember lead poisoning is the main cause of basilic
stickling there's a cell called in achy OFCY or a birth cell, which has regular uniform likes all over at
surface. So remember regular spikes. So burst cells are seen in uremia renal failure, and they can also
sometimes be seen in PIIC kinase deficiency.

Speaker 2:
And there's a similar looking cell called a spur cell or the proper term for this is an a cany. These cells are
also spikey, but they are irregularly spiked. So the spacing of the is irregular and the size of the spikes is
irregular. Some are big, some are little Aytes are seen in liver disease and a beta lipoprotein AMIA spy
are red cells that lose their BI concave shape. So they become spherical. And the classic condition where
you see these is called hereditary SPH cytosis cytes are fragmented red blood cells, leftover pieces of red
cells that have been chopped up. So imagine you have DIC or TTP HS, where you have pathologic
intravascular clotting and a huge network of fibro strands inside the blood vessels and red cells are being
forced through that fibro mesh. So the cells get snagged on the fi or a slice of the cell just gets sheered
off.

Speaker 2:
So again, a shift site is a fragmented red blood cell. Then the next one is target cells, which are really
easy to identify because they look like a bullseye or a target, and they're much easier to identify than
Walmart cells or JCPenney cells. There are a couple of different monic to help you remember the
diseases that cause target cells. But I like the monic, th T H a L, because that helps you remember the
thalasemia is one of them, the HS for hemoglobin C disease, the a is for asplenia and the L is for liver
disease. So with liver disease, you can see target cells. And then what other pathologic form do we just
say? You could see with liver disease Aytes or spur cells. Now here, you see sickle cells which are sickle
shaped or Crescent shaped. And obviously we see these in sickle cell anemia and then a how jolly body
is the basilic remnant of a nucleus in a red cell, which we see in patients with a SNIA no spleen, maybe
they had trauma to their spleen and it ruptured and they had to have it surgically removed, or
sometimes patients with immune thrombocytopenia will have their spleen removed surgically to treat
the ITP patients with sickle cell disease will infarc their spleens over and over through the years until
basically there's no functioning spleen tissue left, but any of these patients with a PLE for any reason
could potentially have how jolly bodies in their red cells, a similar looking finding is called Heinz bodies.

Speaker 2:
So he's bodies are the, these little clumps of denad hemoglobin, which shouldn't be there. And as these
red cells pass through the spleen, the splenic macrophages just bite the Heins bodies, right outta the
cell. And that leaves something called a bite cell. Now think back, when did we mention bite cells and
Heins bodies and oxidative damage to red cells before G six P D deficiency. Remember patients with G
PD deficiency are sensitive to certain drugs that cause oxidative damage like sulphide and D zone, and
also fava beans. That's a classic one. Now, do you remember the Ponic? It was spleen purges, nasty
inclusions from damaged cells, which stands for sulphides PRI Aquin nitrofurantoin, Isan fava beans D
zone and chloroquine. So make sure you know, those, we talked about this back in biochemistry. When
we talked about the HEO mono phosphate. She, so patients with G six P D deficiency, can't go through
the Hm.

Speaker 2:
Phu. So they can't generate reduced glutathione. So their hemoglobin gets oxidized and it forms Heinz
bodies. And then the splenic macrophages remove the Heins bodies and that results in bite cells. And
one other thing, it might be tricky to tell a Heinz body from a how old jolly body, but a how old jolly body
is a remnant of the nucleus. So a red cell might have many Heinz bodies, but it can only have one how
old jolly body per cell. So for Hines bodies, think about Heinz 57 O 57 is a big number. So you can
potentially have lots of Heinz bodies in a cell. There are teardrop cells which are shaped like teardrops,
and they're seen with Mylo fibrosis. You can also see elliptical shaped red cells, which are called elliptic
bytes. And these are seen in something called hereditary elliptic. Cytosis sometimes you may hear these
called pencil cells or cigar cells.

Speaker 2:
And finally, I wanna discuss Ciro blast and ring Ciro blast for just a second, because this is potentially
confusing and it gets mixed up a lot. So, first of all, what is a Ciro blast? A Ciro blast is a nucleated red
cell precursor that has granules of iron in the mitochondria. And CTER blast are found in the bone
marrow of new normal, healthy people. So sitter blasts are perfectly normal. They're not pathological.
And again, they're found in the bone marrow, not in the peripheral blood. However, if you have a
disorder that affects, he synthesis the sitter blast, can't use all the iron that's stored in those iron
granules. So they have too many granules and the iron granules sort of surround and encircle the
nucleus. So they form a ring around the nucleus. Now we call this a ringed sitter blast. So sitter blasts
are normal, but ringed sitter blasts are abnormal.

Speaker 2:
And where do you find these rings? Sitter blast. Again, they're found in the bone and marrow, not the
peripheral blood, but the bone marrow. Now patients with disorders of he synthesis are gonna be
anemic. And when you do a bone marrow biopsy, you're gonna see large numbers of these abnormal
ring clasts. So these diseases are said to cause Castic anemia. Now lots of different things can cause
Castic anemia, certain genetic conditions, certain drugs, chronic alcohol use and myelodysplastic
syndromes. So Castic anemia, isn't a diagnosis in and of itself. It's a sign of some other underlying
disease. Now you may sometimes see lead poisoning listed as a cause of Castic anemia, but that's not
really well documented. We're gonna talk about lead poisoning in the next video. Now, before we move
on, let's do a quick whiteboard review to help make sure you have all these terms really locked down for
this whiteboard review. We're gonna match these terms on the left, written in blue with the definitions
written in green on the right. So the first term is an a can site. And that's another name for a spur cell,
those red cells with irregular spike. What diseases did we say? We saw the Aytes or spur cells in liver
disease and in a beta lipoprotein AMIA. Now the next one is DEMA site and I'm kind of sneaking this one
in, because a DCY is another name for a bite cell.

Speaker 2:
Next we have akin OFCY and akin are those cells with the regular uniform spikes. You said the other
name for those were the bur cells. The next one is erythrocyte, which is just a normal name for a normal
red cell. Then Hines bodies, Hines bodies are those oxidated hemoglobin bodies that are found in the
red cells precipitate out in the red cells in patients with G six PD deficiency. Then how jolly body is the
nuclear remnant that are found in red cells in patients with Alania. Then meticulous site is a name for an
immature red cell. A shift to site is a fragmented red cell that we see in pain with DIC and other forms of
microangiopathic hemolytic anemia. And then aspheric side is obviously a spherical red blood cell. So
good job with those next. I wanna talk about a couple of topics related to blood transfusions.

Speaker 2:
So first of all, there are several different types of blood products that you might be transfusing. The
most common a product had transfused it's packed red blood cells or PBCS. These are red blood cells
that have been separated from the other donor blood components. So it's concentrated red blood cells,
which we usually give to patients that have significant anemia, especially from acute blood loss, from
trauma, or maybe a GI hemorrhage or maybe from surgery. And you can kind of reason out why we
would give red cells. Patients with anemia have decreased hemoglobin. So we want to increase the
oxygen carrying capacity. We transfuse platelets for certain types of thrombocytopenia, especially if
there's active bleeding due to thrombocytopenia, or if a Thrombocytopedic patient needs to have
surgery. And you're worried about post-op bleeding or possibly you might give platelets to a patient
whose platelet count is normal, but the platelets themselves are defective so that the patient can't stop
bleeding.

Speaker 2:
Sometimes we transfuse fresh frozen plasma or FFP, which is a plasma from which the red cells and
other cellular components have been removed. So it's basically serum the water and electrolyte portion
of the blood plus the plasma proteins and the cloting factors. Now FFP is sometimes given to patients
with a cloting factor deficiency, like in a patient with cirrhosis whose liver isn't making cloting factors or
in disorders like DIC or thrombotic Thrombocytopedic per TTP. Both of these are disorders in which
there's widespread, intravascular COAG and all the cloting factors are being consumed. But the idea
here is to give FFP, to replace the coagulation factors that are missing. Now there's a similar blood
product that we give to patients with a warfarin overdose who are bleeding, and we need to rapidly
reverse that anticoagulation. Do you remember what that blood product was? It's called pro thrombin
complex concentrator PCC, which is an infusion of the vitamin K dependent coagulation factors, which
are factors 10, 9, 7, and two.

Speaker 2:
Then one more blood product you might transfuse is called cryoprecipitate. This is similar to FP or PCC,
but you basically thaw the FFP and you collect just the cloting factors, especially FibroGen and factor
eight, and also some V Willand factor. So you can use it for patients with DIC or TTP, cuz these patients
are consuming all their FibroGen. So you can give cryoprecipitate just like you would FFP, or you might
give it to a patient with hemophilia a where you wanted to give factor eight, but overall we don't use
cryoprecipitate much anymore. It's more common to give specific cloting factors that have been from
multiple donors. So if you have a patient with factor eight deficiency, you just give pooled factor eight
rather than cryo. And just to mention briefly, the risks involved with giving transfusions include things
like iron overload. So you have a patient who receives a ton of packed red cells.

Speaker 2:
If they weren't iron deficient, they could end up with too much iron and they can get hemochromatosis
from that. They could develop up some hypocalcemia because red cells are stored with sodium citrate
to prevent coagulation of the blood. And when that citrate gets transfused, that citrate combined to all
the patient's calcium and that can lead to hypocalcemia, a patient could develop hyperemia. If the red
cells have been sitting in storage long enough that some of the older red cells have started to life and
the intracellular potassium spills out into the tr transfusion fluid. And there's a very small risk of
infection because we screen blood donors for all sorts of infectious things like HIV and viral hepatitis and
so on. And of course there's a risk of transfusion reactions, which are discussed in the immunology
videos. And speaking of transfusion reactions, make sure you review the blood types or ABO blood
groups.

Speaker 2:
Now you probably learned everything you need to know about ABO blood types back in high school
biology. I don't really have much to add that you probably don't already know about that. So you can
review those on your own if you need to. But two quick things, I do wanna point out, first of all, what
happens if you transfuse an incompatible blood type where you're gonna get an antibody mediated type
two hypersensitivity, right? Circulating antibodies, bind to the cellular antigens, and that leads to
hemolysis fever, possibly shock kidney failure and death. And then what's the number one cause of
transfusion reactions. It's clerical error, somebody goofed on the type and cross or somebody
mislabeled the blood or got delivered to the wrong floor or whatever. So you're gonna see the nursing
staff going through this huge checklist, checking the patient's ID bracelet, checking the labeling on the
blood products, being extra cautious because these transfusion reactions can be really dangerous, but
they're pretty much totally preventable.

Speaker 2:
There's one disorder of related to blood type incompatibility that you should know something about,
which is erythroblastosis fats. And that's specifically due to RH incompatibility. So take a look in the
study guide. Erythroblastosis fats occurs due to maternal antibodies against fetal red cell antigens,
typically antibodies to RHD. So RH negative moms who don't have that RHD antigen on of their red cells
do not naturally have antibodies to RHD. It's only after mom is exposed to RHD antigens on the RH
positive baby's red cells that mom starts developing antibodies. So this exposure may occur during the
first pregnancy with an RH positive baby, but these antibodies don't cause problems during that first
pregnancy, the antibodies only develop in a abundant enough to cause problems in subsequent
pregnancies. So if there's any trauma or something where the baby's blood comes into contact with the
mother's blood, which could include delivery.

Speaker 2:
So if the baby's blood comes into contact with mom's blood during that first pregnancy mom's immune
system becomes sensitized to the RHD antigens and mom starts making anti RHD antibodies. Then on
subsequent pregnancies, if the baby is RH positive, the moms anti RHD IgG antibodies can cross the
placenta and attack the fetuses red cells. So the clinical features of an neonate with erythroblastosis
fatals include anemia due to hemolysis of those fetal red cells. And then those cells Heide hemoglobin is
gonna be released. And that hemoglobin is converted into Billy Rubin and the Billy Rubin causes jaundice
and possibly ConnectUS in the neonate. The fetus can also develop hydrops fats, which is a generalized
fetal edema and be aware that erythroblastosis fats is life-threatening and it can cause intrauterine
death. So what do we do to prevent all this? Well, we give RH negative moms, anti RHD immunoglobulin
at 28 weeks, or whenever there's any type of trauma, like a motor vehicle accident, or anytime there's
an abortion or miscarriage.
Speaker 2:
And also within three days of delivery, basically anytime the mom might be exposed to the fetal red
blood cells, you're gonna give anti RHD immunoglobulin, which is IgG to sort of hide those fetal red
blood cells so that the mom's immune system never sees them. Once the mom's immune system starts
seeing those fetal RHD antigens, she's gonna develop an immune response to them. So we hide the RHD
positive, fetal red cells by giving anti high RHD immunoglobulin. So that mom never develops that
immune response. So again, the scenarios where the mom's immune system is likely to see those red
blood cells would be after 28 weeks because you're more likely to deliver after 28 weeks and at any
traumatic event where you might have mixing of blood crossing the placenta and also within the first
three days of Del delivery. So now it's time for the intercession quiz. So pause the video and answer
those questions. Then restart the video and we'll go over the answers together.

Speaker 2:
First question, what allows red cells to change shape is a pass through vessels. That's the protein
spectrum. Next? What name is the given to immature erythrocytes and circulation? We call them
reticulocytes. Next one. What pathologic form of red cell would you see in the following diseases? So
with lead poisoning, you see red cells with basilic sting, with G six PD deficiency. You might see bite cells
and also Hines bodies within the red cells with DIC. You're gonna see cytes with a beta lipoprotein AMIA.
You're gonna see Aytes which are also called spur cells. And with asplenia you might see how old jolly
bodies and also possibly target cells. And that's it for now. I'll see you next time.