Erythropoiesis and Anemia Flashcards

1
Q

Definion of Erythropoiesis

A

Formation of Red blood cells

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2
Q

What part of Erythropoiesis takes 7 days?

A

progenitor cell (pluripotent stem cell) to the release of the reticulocyte in the circulation takes about 7 days

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3
Q

What happens when the reticulocyte is out in the circulation?

A

Reticulocytes retain remnants of RNA and polyribosomes to continue synthesizing hemoglobin (manufacture protein)

in 48 hours, the RNA and polyribosomes are kick out and the reticulocyte is now a mature erythrocyte

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4
Q

Erythropoietin (EPO)

A

Influences the rate of RBC production.

Made in the kidney ( this is an exception). Only about 10-15% secreted by the liver.

It is inactivated by the liver

Stimulates progenitor stem cells to differentiate into erythrocytes

Increases the rate of mitosis of RBC precursors.

Lots of EPO, quick mitosis, lots of RBC

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5
Q

What is the clinical danger of a large amount of blood loss?

A

It takes 7 days for mature erythrocyte (RBC) to be formed and therefore, need to monitor amount of blood for 7 days until it can be replenished.

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6
Q

How are erythrocytes formed?

A

1) In the presence of EPO (erythropoietin), that is formed in the kidneys in response to hypoxia (O2 deficient), stimulates production of RBC in the bone marrow.
2) Erythroblast loses its nucleus and mitochondria ( phagocytosed by a WBC) and it is an immature reticulocyte. (this takes 7 days)
3) reticulocyte comes out of the bone marrow into circulation and matures into an erythrocyte. within 48 hours

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7
Q

Erythrocyte shape importance

A

Biconcave shape important because :

Once the ability to repair is lost when RNA and polyrobosomes are removed (no more protein synthesis), the blood cell has no way to repair if damaged.

-The biconcave shape is super flexible, and is resistant to some degree of breaking.
Can pass through narrow capillaries without bursting or blocking the flow

  • they can change shape in response to osmotic changes
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8
Q

Hypotonic solution

A

Swells RBC’s.

Lose too much salt, or too much water in the cell.

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9
Q

Hypertonic solution

A

Shrinks RBCs. this happens in the presence of increased salt or decreased H20.

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10
Q

Sickle Cell Anemia

A

Genetic mutation. The Hb crystalizes with a change in O2 concentration (sickness or altitude) and causes the cell to sickle.
These crystalized cells are not flexible, can form clots, and are very sharp and painful.

The reason it still exists is the resistance to malaria.

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11
Q

How long to erythrocytes live?

A

about 120 days before they are eaten by the spleen and the components are recycled.

Amino acids (made into new proteins), cell membranes, and iron are all recycled.

We only excrete the ‘heme’ part of hemoglobin by converting the heme groups to bilirubin, and excrete them as bile.

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12
Q

Too much of what protein results in jaundice?

What about babies?

A

Too much bilirubin built up in the blood can cause jaundice.

Babies often born or develop jaundice because in vitro they have a special type of Hb that has more affinity for O2 to steal from mom. As soon as babies take their fist few breaths they are required to start synthesizing their own. Because the liver needs to break up all of the bilirubin in their system, they can become jaundiced because it is a lot of work for their liver.

Treatment : incubate babies with UV light which breaks up the bilirubin so the liver can do a better job and recover faster.

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13
Q

Hemoglobin (HB) Structure

A

a tetramer of 2x2 proteins, and 4 binding sites for oxygen

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14
Q

Iron Utilization

A

Absorbed in the diet through the small intestinal wall via active transport ( needs energy).

Transported to the bone marrow, bound to transferrin (chauffeur that drives iron everywhere), and stored within the ferritin (storgae form of iron) which is found in the liver.

Fe is incorpoated into the Hb within the newly formed RBC and relased into circulation

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15
Q

Best way/ most practical way to measure iron clinically

A

Best way : bone marrow biopsy. This is too invasive to be practical.

Way we look at it : ferritin. Drawbacks ; it is the storage form and therefore, the last thing to drop when we are iron deficient.

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16
Q

What sources of iron can we utilize?

A

Best : heme, animal iron. our bodies are well adapted for this.

non - heme iron. from plants, still usable.

*many vegs/vegabs do not have a problem with iron which meat eaters might be anemic.

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17
Q

Why do we care if we have enough iron?

A

We will not make enough blood cells if there is not enough iron to put into them. Not enough blod = not enough O2. Can be fatal!

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18
Q

Explain Iron Metabolism Graphic

A

1) Iron from the diet is metabolised in the intestine.
2) Iron enters into the plasma (of the cell, membrane?) absobed by active transport.
3) Transferrin transports iron in the plasma and can either go one of 2 ways :
i) stores Fe as ferritin in the liver.
- liver metabolises bilirubin and excretes it in bile
- bilirubin metabolites are excreted in feces and urine.
- iron is recycled and transported to the liver for storage or intoduced to the Bone marrow for RBC production

or

ii) Bone marrow uses Fe to make Hemoglobin (Hb).
- fe –> heme–> Hb –> RBC synthesis

  • spleen converts Hb to bilirubin
  • liver metabolises bilirubin and excretes it in bile
  • bilirubin metabolites are excreted in feces and urine.
  • iron is recycled and transported to the liver for storage or intoduced to the Bone marrow for RBC production
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19
Q

Anemia

Definition and general causes

A

Results when Hb or RBC counts are too low for normal physiological function

Generally caused by increased RBC loss or decreased RBC production

20
Q

Types of Accelerated RBC loss - Anemia

A

General Blood loss :
due to hemmorage ( bleeding)
- cells are notmal in size and Hb content but low in number.

Mostly ER situations, heaby menstruation, uterine fibroids.

OR

Hemolytic anemia :
cells rupture at a high rate.
- hereditary due to enzyme mutations, like sickle cell)
- acquired ( malaria, drugs (chemo), parasites, or autoimmune reactions)

21
Q

Aplastic anemia

A

Decreased RBC production.
aka bone marrow failure. All cellular elements decreased.
inadequate EPO production.

  • no RBC, no WBC production, damaged kidney etc.
22
Q

Inadequate dietary nutrient anemia

A

Iron deficiency :
low iron results in few RBC’s that are smaller and contain less Hb than normal cells. Not enough FE stops RBC synthesis - doesn’t want to waste resources to make empty cells.

Folic Acid and B12 deficiency :
- needed for DNA synthesis and cell division
-low levels result in slower protein synthesis resulting in fewer RBCs that are larger than normal due to slow cell division.
- they get locked in the G2 phase and cannot do mitosis.
megaoblasticanemia

23
Q

Hemoglobin on CBC

A

amount of Hb in the blood. O2 carrying capacity.

amount per unit volume.

Best for diagnosing anemia

24
Q

Hematocrit (Hct)

A

Percentage of RBCs in the given volume of blood.
Cellular component to fluid volume

Not that reliable, to diagnose anemia. changes with hydration.

25
Q

RBC count on CBC

A

RBC count per given volume of whole blood

If this is low second test to diagnose anemia

26
Q

Red Cell Distribution Width (RDW)

A

Size variation of RBCs. Unitless measurement statistically derived.
Doesn’t pick up actual size, only the variation

27
Q

WBC on CBC

A

White Blood Cells count per given volume. Not very specific. Neutrophils make up 50-60%

28
Q

Platelet

A

count of platelets per given volume of whole blood

too high : clotting disorder
Too low: bleeding disorder

29
Q

Mean Platelet Volume ( MPV)

A

Average size of the platelet. New platelets are larger in size

30
Q

Mean Corpuscular Volume

A

Average Volume size of a single RBC

Macrocytic : too big, B12 or Folic Acid deficiency
Normocytic : normal size
Microcytic : Too small, Fe deficient

31
Q

Mean Corpuscular Hemoglobin

A

Average amount/weight of Hb within 1 RBC

32
Q

Mean Corpuscular Hemoglobin Concentration

A

Concentration/percent of Hb in 1 RBC (Hb/Hct)

Hypochromic : not enough colour in the RBC

Normochromic : normal colour

33
Q

Microcitic Hypochromic

A

Iron Deficency Anemia

34
Q

White Blood Cell breakdown into subtypes

A

Neutrophils (55-70)

Swings high and then low after a viral infection. High to fight and low for depletion.

Eosinophils (1-4) (usually always high - related to allergies and parasite)

Lymphocytes (02-40)
Basophils (0.5-1.0)
Monocytes (2-8)

L+B+M - usually not outside reference range

35
Q

MCHC and MCH Similarity

A

Usually go the same way : Both say the same thing

36
Q

What will the diagnosis be if the cells are big and MCH and MCHC are normal?

A

Consistent with a B12/Folate deficiency

37
Q

CAMs

4 families

A

Integrins : large family involved in cell -cell and cell BM adhesion. Cell/Cell

IgG Superfamily : membrane bound immunoglobulins : Y shape. Stick on Cell Surface and other things

Cadherins : calcium dependent. Proteins only bind in the presence of Calcium

Selectins : lectin like binding domains ( bind sugar moieties ( bind sugar groups)

38
Q

Intercellular collections ; two broad classifications

A

1) Connections that are structural ( cell fasteners)
Tissues to move as time & not individual cells want fluidity

2) Connections that permit ion/molecular transfer. Gap junction, cell to cell connection that allows molecules to pass between them. Tissue acts as tissue, not individual cell movements.

39
Q

Demsosomes

A

Acting filamant pokes from one active filament into the other filament of another cell

40
Q

Tight Junctions

A

Structural linkage. glues neighbour cells together. We don’t want anything going in between cells because that is unregulated absorption. Only H20 and small ions should be able to get between cells.

41
Q

Microvilli

A

So we can absorb lots of stuff.

42
Q

Hemidesmosomes

A

Half of a desmosome. Anchor the cells on the basement membrane. like sticky shoes, lifting up and putting down again to decrease mechanical stressors ( quite dynamic) Communicate with the cells : ECM and cell skeleton

43
Q

Gap junctions

A

Collection of connections of ion and small molecule transfer. H2O, Na, Ca2+, flow between cells.

Comprised of 12 protein units called connexins (6 from each cell : one on top one on the bottom)

6 connexins = 1 Connexon

Allows for intercellular communication/ activity without entering the ECF

Function like large fields that are all in one area.

44
Q

Zonula adherens

A

located basal to tight junction (belt)

filaments have an association and a structural link for stability but allows for fluidity in tissues.

ex) Don’t want a rock hard liver

45
Q

Tight Junctions :

What are they?
What are they made of?
Why are they important?

A

AKA - Zona occulens

typically surround apical margin of epithelial cells

Ridges composed of :

Occulin and Claudin which are potroteins that bond tightly to minimize the space between cells.

and JAMS (Junction Adhesion Molecules) which are an Ig type adhesion molecule

Why is this important? Stops This paracellular pathway, proteins cannot pass through the cells, We want a one way road for proper regulation

46
Q

Clinical Importance of Tight Junctions

A

Disruption of the tight junction is associated with changes of the cellular permiability.

Examples :
Infectious diarrea. E coli causes occulin redistribution

Cholera : occulin protease ( enzyme that breaks down a protein)

Not limited to GI disorders : BBB disruption due to HIV