3. Anemia Flashcards
Anemia - Epidemiology • 400 different clinical variants • Estimated 33% of global population • Most common \_\_\_\_ disorder in US • More prevalent in \_\_\_\_
- Let’s define anemia: a plethora of diseases that fall under one category. There are several different variants of anemia.
- Most common: ____ deficiency anemia, ____-deficiency anemia, and ____ deficiency. Beyond that, almost all nutrients discussed last week can also be deficient in some patients, which will result in anemia.
- There are also genetic forms of anemia, such as ____ & ____ anemia. (He will discuss those today as well)
• In reference to picture:
◦ This is a v prevalent disease
• DON’T MEMORIZE THE CHART.
• Chart reflects how prevalent anemias are in different parts of the world. Bright red indicates high prevalence.
• In africa, high prevalence because those patients are at a higher risk of sickle cell anemia (genetic).
◦ In africa, patients with sickle cell anemia are resistant to the effects of ____, and those who don’t have it are more prone to malaria. This is bc malaria needs normal blood cells in order for organism to propagate it’s disease.
blood
elderly
iron vit-B12 folic acid thalassemia sickle cell
malaria
• While it’s more commonly found in elderly patients, it’s not considered an ____ person’s disease.
• Any age range may be afflicted by this condition.
• As this population in this country is getting older, we’re seeing more and more of it in older ____, for
a variety of different reasons.
‣ Most commonly bc of ____ (or lack thereof) or side effects of ____ (resulting in
anemic states).
old
patients
nutrition
medication
Anemia – Causes
• Acquired – \_\_\_\_ – Nutritional deficiency – \_\_\_\_ disease – Pregnancy / excessive menstruation
• Genetic diseases
• Trauma is most common.
◦ Referring to picture (which is actually a gif lol): in Canada, hockey game on Saturday nights is THE thing to do. Live game, Buffalo Sabres playing. Goalie (Clint Malarchuk) got sliced in the neck with a skate and starts spurting blood all over the ice. He experienced a traumatically induced anemia. Fun fact: subsequent to this accident, goalies started wearing neck shields.
◦ Blunt trauma (any kind resulting in excessive blood loss), will cause anemia due to reduced volume of blood. That anemia won’t manifest with any ____ lab findings beyond ____ # of RBC, Hct ____.
• Reads slide- these are the most common causes of acquired anemia, but there are others.
• Second category is genetic diseases.
trauma chronic abnormal lower lowered
Anemia
• Decreased number of circulating RBCs
– Reduced or faulty production
– Increased destruction (hemolysis)
– Increased blood loss (hemorrhage)
• Anemia is defined in one of 3 ways primarily.
◦ Either not being produced sufficiently, or released/destroyed excessively.
• Beyond that, in regards to destruction, if the spleen is in ____, that results in ____.
◦ If you have a disease that activates your spleen, that could also result in anemia because the spleen is
now destroying more RBCs than it should be.
hyper-drive
hemolysis
• Don’t memorize this list- These are by far some of the most commonly occurring complications that patients with anemia manifest.
• These ____ are irrespective of what type of anemia they have. Whether it’s macrocytic (B12 or folic acid), microcytic (iron), sickle cell, etc.
• There are also oral manifestations.
◦ Some of the most common oral manifestations are: ____ of the tongue (glossitis), ____ mouth, ____, ____, localized or generalized ____, edema.
◦ AGAIN: not unique to any one type of anemia, but common to all! (really emphasized this).
signs/symptoms/complications balding burning angular cheilitis candiadiasis edema
Referring to picture of hands on the right: this (on left) is a woman who’s ____, vs her husband who is not. With anemia, they have ____ colored skin.
anemic
paler
• Don’t memorize this chart, strictly for informational purposes.
• He emphasizes this concept AGAIN: Irrespective of the ____ state, manifestations are not that ____.
◦ B12 deficiency will do the same thing as ____ deficiency. Folic acid deficiency will do the exact same thing as ____ deficiency. (Clinically, not mechanistically).
• There are distinct differences between these ____, but they are typically at the level of ____ findings. Clinically speaking, most patients with anemia will manifest with a v similar pattern.
deficiency dissimilar B12 anemias lab
Erythrocytes = Red blood cells
• Produced in bone marrow via ____ stimulation
• Progenitor → ____ → Mature RBC
• 2 million new cells / sec
• 120 day life span
• After maturation - Don’t grow, don’t divide, don’t make new proteins
• Kidney produces ____
• EPO goes to the bone marrow where it helps to stimulate RBC formation
◦ RBCs go through an array of maturation steps
◦ All types of RBC have the same ____ cells, which then differentiate along different lineages based on need and certain signals.
◦ Progenitor RBC matures to ____, and further matures to a mature RBC.
‣ A mature RBC is ____, has a ____ disc shape, looks like a cheerio without a hole.
• Have a pretty short life span- about ____ months long.
• After a mature RBC forms, it doesn’t ____ any further, and doesn’t produce any additional protein.
What the mature cell has, it ____ until it’s death.
• Dies through the spleen.
erythropoietin reticulocyte erythropoietin (EPO) progenitor stem reticulocyte anuclear biconcave 4 mature/divide retains
Hemoglobin (Hb)
- Heme binds ____ which binds oxygen
- Blood bright red when Hb is ____, dark red when deoxygenated
• All RBCs carry Hb, which in turn carries oxygen.
• Hb is composed of 4 chains, each chain contains 1 iron molecule, and each iron molecule contains ____
oxygen molecules.
◦ 1 Hb can carry up to ____ oxygen molecules- when blood is bright red, it is oxygenated. When it’s not as
bright red, it is deoxygenated
Fe
oxygenated
one
4
Normal red blood cell indices
- Red & Green boxes (larger pics below): We need to know how to illustrate & interpret these routine lab tests in a written chart.
- Don’t need to know the normal values, but know what they ____.
- We may see these in our patient charts or in residency in hospital setting.
depict
What the indices mean
HCT – volume percentage of ____ in blood
• MCV – average ____ of RBC
• MCH – amount of ____ in average RBC
• MCHC – average ____ of Hb in average RBC
• RDW – measures variation in red blood cell ____ or red cell volume
RDW = Red cell distribution \_\_\_\_ HCT = packed cell volume = erythrocyte \_\_\_\_ fraction
• He basically just reads the entire chart & the slide, I added anything extra he said. • HCT- hematocrit, represents the volume of RBC in a tube that you've drawn the blood into. Explaining the pic on the right: Once you centrifuge the blood, the packed volume on bottom represents the amount of RBC. Divide by total volume in tube- that ratio is HCT. Men tend to have a higher hct than \_\_\_\_, so theres a range of normal. • MCV- In a hospital setting, you put blood into a machine and it will average the size of the RBCs. • MCH- Parameter that defines how much Hb is carried by a RBC. • MCHC- \_\_\_\_. • RDW- measures any variation in either size or width in RBC (or irregularly shaped). Will increase relative to normal (whether the size is too small or too large, it'll still increase- it's NOT proportional). Most anemias will have an \_\_\_\_ RDW. • Know these parameters, know how to define them, but don't need to know the normal values.
RBC size Hb concentration cell size
width
volume
women
MCH/MCV
elevated
Why these indices are important
Alterations in HCT
Elevated RDW = anisocytosis
• Any change in any of these numbers reflect an abnormal phenotype (some abnormality of the blood).
• This cell (in purple) is much larger than the cells adjacent to it, and this cell (in orange) is much smaller
than the ones adjacent to it.
◦ Represents different sizes of RBCs, causing an ____ RDW. This is synonymous with
____. It implies a change in cell ____. Know what this term means.
• Another term called poikilocytosis, is also ____ RDW, except it implies a change in cell ____. A patient who has ____ anemia (sickle cell blood cells look like a sickle lol).
elevated
anistocytosis
size
RDW
chape
sickle cell
Why these indices are important
• Referring to chart on left:
◦ if the MCV is smaller than normal, implies ____ anemia.
◦ if the MCV is larger than normal, implies ____ anemia.
◦ BUT some anemias may be ____- normal cell size, hence a normal MCV.
• Referring to chart in center:
◦ the higher the mean MCH, the darker the cell (microscopically)- called ____.
◦ the lower the mean MCH, the lighter the cell- called ____
◦ if MCH is normal range, its called ____
◦ you CAN have anemias that are normochromic, where there is no change in coloration of the cell.
• Referring to chart on right:
◦ MCHC is ratio between MCH/MCV.
◦ Microcytic hypochromic is if MCHC is ____ normal.
◦ Microcytic hyperchromic anemia is if MCHC is ____ normal.
◦ If MCHC is normal range, the patient will have macrocytic ____ anemia.
◦ To rationalize this, try to plug #s into this equation to understand WHY they’re defined this way.
microcytic
macrocytic
normocytic
hyperchromic
hypochromic
normochromic
below
above
normochromic
Microcytic
- ____ deficiency
- Thalassemia
Macrocytic 1. \_\_\_\_ deficiency 2. Folic acid deficiency 3. Drug-induced (NOT anemia just \_\_\_\_) 4. Leukemia (NOT anemia just \_\_\_\_)
Normocytic Anemia of \_\_\_\_ disease Hemorrhagic anemia \_\_\_\_ disease Hemolytic anemia Aplastic anemia
• •
•
The anemias are subclassified based on the cell ____ primarily: Micro, Macro, Normo-cytic
Some categorizations also sub-classify based on color: hypochromic vs hyperchromic (more reliable means of subclassifications).
Today’s discussion will focus strictly on actual anemias: iron deficiency, thalassemia, vitB12 deficiency, folic acid deficiency, and the 5 under normocytic.
◦ We will NOT focus on 3 & 4 under macrocytic (underlined). Included bc a blood smear may show enlarged RBCs without being the result of anemia (could be leukemia, drug-induced phenomenon).
iron
vitamin B12
macrocytosis
macrocytosis
chronic
sickle cell
size
Iron deficiency anemia
- Most ____ anemia – Young women, kids
- ____
- always, irrespective of causation
- Hb, HCT, MCV, MCH and MCHC < ____
- All these parameters will be below normal levels.
• Its the most commonly occurring acquired anemia in the world- specifically in this part of the world.
• Affects a whole age range of patients, but most common anemia of ____ people, especially kids/
young adults.
• In ____, during menstruation, especially those who have excessive/heavy periods, you’re at risk for developing Fe-deficiency anemia. A common therapeutic approach is iron supplement pills.
• In children, it’s obv not menstrual blood they’re losing, they just haven’t ____ their body sufficiently
enough to retain enough iron, so even they would be given iron pills to supplement.
◦ Therapy is actually quite easy in most cases, especially if iron-deficiency anemia is simply a
consequence of reduced blood levels
• Without knowing what values represent, its intuitive as to why it’s microcytic, hypochromic: if Hb doesn’t cary enough iron, RBCs dont carry enough ____- therefore microscopically they will appear less red/ more pale. Due to this, the cells don’t need to be that big, hence why they’re smaller.
common
microcytic-hypochromic
normal
young
children
developed
oxygen
Iron deficiency anemia
• Multisystem and immunologic disorder
• Again, don’t memorize this chart, except to say that these are some of the most commonly occurring complications in a pt with ANY anemia, including iron-deficiency anemia.
• Some anemias DO have more characteristic phenotypes- iron deficiency will result in increased risk of ____ (iron is a requirement of the immune system, so it’s weaker).
◦ Beyond that, because it’s hypochromic, their skin color is more ____.
infection
pale
◦ ____, balding tongue, pale ____: these are not unique to iron-deficiency anemia.
angular chielitis
hands
Diagnosis of IDA
(Referring to diagram on the left): The other day we talked about the molecular pathways used to absorb and transport iron. We have to know the pathways for iron transportation, export, and storage.
◦ Quick synopsis: Fe is stored/bound to a protein called ____ inside the cell. Once it goes into the bloodstream, it gets transported anywhere it needs to go by binding to ____ (an iron-binding protein in blood). These are two proteins (ferritin & transferrin) we can use as part of a panel of tests in IDA.
Referring to chart on the right for Iron Panel Tests: We need to know the different tests used to measure iron!!
ferritin
transferrin
Diagnosis of IDA
◦ Serum Iron: ____ in IDA (self-explanatory)
◦ Serum Ferritin: If serum iron is reduced, then ferritin will be ____ proportionally (because it’s not needed to bind iron).
◦ Transferrin: levels would ____ in patient with IDA!! There’s a lack of iron in the blood stream,
the body senses a need for more iron in the blood stream, and it thinks it’s not producing enough transferrin to bind the iron. So it then produces more transferrin in hopes of capturing all available iron for normal functionality.
◦ Hemoglobin: would ____ (reduced) bc it’s not carrying iron.
◦ TIBC: Measures what capacity the blood can carry iron. Since the only protein in the blood that carries iron is transferrin, TIBC can be used to indirectly measure transferrin. Increased transferrin, means an increased binding capacity, leads to ____ TIBC.
◦ Transferrin Iron saturation percentage: a measure of Total serum iron concentration/TIBC. This ratio would ____. “And why? because” (hehe)- If TIBC is elevated (denominator is larger), and serum iron is decreased (numerator smaller), this equates to a smaller percentage.
reduced reduced increase drop increased decrease
• Referring to left picture:
◦ This is a picture to illustrate a normal blood smear (arrow just illustrates a WBC).
◦ Take a droplet of blood, put it on a microscopic slide, stain it with a special stain, put a cover slip and
put it under the microscope.
◦ Most blood cells look pretty ____ in size and coloration, and quite a lot of cells.
• Referring to right picture:
◦ Contrast this to the same amount of blood applied to the slide as the one on left, except FAR ____ cells (anemic by definition), but also different sizes, different shapes.
◦ This cell has an elliptical shape, exhibiting ____.
◦ Some cells are larger than others, exhibiting ____.
◦ The third thing we’re seeing is that some of these cells have a clearing within them. The more clear that you see (donut shape), implies ____.
◦ Fourth feature is the really tiny cells, implying ____.
◦ This process, seen collectively on this blood smear, is poikilocytosis and anisocytosis.
uniform fewer poikilocytosis anisocytosis hypochromia microcytosis
• Anisocytosis
– RBCs of ____ size
– ____ RDW
• Poikilocytosis
– ____-shaped RBCs
unequal
increased
abnormally
Iron supplementation
• Not gonna go through this, we had this the other day.
• Just to reiterate that you get iron from both ____; they come in two different forms, but
they’re both used the exact same way.
plants and animals
Plummer-Vinson syndrome
Chronic, severe ____ deficiency
____, dysphagia
____, glossitis
Increased esophageal, hypopharyngeal ____
◦ Either way, it’s chronic & severe. It has an array of distinct complications, including increased risk for cancer (specifically base-of-tongue, esophageal SCC (?)).
‣ Iron, for whatever reason, is used in that part of the body by the ____ cells and the absence of iron will increase risk for cancer in that region of the head and neck.
• Nail beds are very severely affected- ____-shaped nails called koilonychia.
• Beyond that, the glossitis/angular cheilitis/edema is not characteristic, it’s common to all anemias.
• What is UNIQUE to Plummer-Vinson is the ____ issues, cancer risk, and the koilonychia.
• How do you treat this? Like any other iron-deficiency, you treat by ____ the iron, assuming they
can absorb the iron properly.
iron
esophageal webs
koilonychia
SCC
squamous
spoon
supplementing
α- and β- Thalassemia
• Diseases of Hb ____ (hemoglobinopathy)
• Most ____ monogenic diseases
• Nomenclature reflects affected Hb chain(s)
• ____ variant more clinically significant form
• unless the patient has very ____ alpha chain deficiency
• ____ anemia (Irrespective of whether it’s alpha or beta)
• Iron deficiency is acquired in almost all cases (there is one genetic form). This is not an IDA.
• In contrast, alpha & beta thalassemia is a ____ form of anemia.
◦ In fact, I would guess that our student population probably has 3-4 people that have this disease. It is a rather small percentage, but is actually a high percentage in the grand scheme of things. It is a commonly occurring genetic disease, and most people who have it tend to be ____.
◦ These are ____ diseases. Both of the thalassemias affect Hb specifically (either alpha or beta, respectively).
synthesis common B alpha microcytic, hypochromic
genetic
asian
monogenic
Hemoglobin (Hb)
we have diff variations of these combinations to make up Hb: \_\_\_\_ α chain genes \_\_\_\_ γ chain genes \_\_\_\_ β chain gene \_\_\_\_ δ chain gene - all Hb molecules have \_\_\_\_ chains
Adults:
HgA-1 - ____ (most common)
HbA-2 -____ (smaller proportion)
HbF - ____ (<1% of adult blood)
Infants - ____
• We discussed Hb synthesis last year.
◦ As an aside, it’s HbA1 that gets glycosylated to form HbA1C.
• HbF is what we’re born with, makes up majority of our Hb during first 12 months of life. ◦ As ____, we have <1% of all of our blood as HbF.
2 2 1 1 4
a2b2 a2delta2 a2y2 HbF adults
