Anaemia

Question 1

Basic development of erythrocyte?

Answer 1

1. Stem cell - B12 and folate
2. Pro-erythroblast - EPO and ferritin
3. Erythroblast - EPO and ferritin
4. Normoblast
5. Reticulocyte - 48hr, anucleus, RNA fragments, some in circulation
6. Erythrocyte (RBC) - Hb to carry O2

Question 2

Normal cycle of RBCs?

Answer 2

1. Red bone marrow
2. Circulation
3. 10% haemolysis: kidney excretion or macrophage recycle (spleen, liver, marrow)
4. 90% ~120 day life -> macrophage recycle
5. Haem -> bilirubin (liver -> kidney or gut)

Question 3

Erythrocyte STIMULATION?

Answer 3

1. EPO
2. Growth factors (eg. G-CSF)
3. Stem cell factor
4. Regulating factors

Question 4

Erythrocyte PRODUCTION (haemopoiesis)?

Answer 4

Early embryo - yolk sac
Foetus - liver, spleen
Child - red marrow in almost all bones
Adult - red marrow in axial skeleton

Red marrow -> RBCs, leukocytes, platelets

Question 5

Erythrocyte MATURATION?

Answer 5

Reticulocytes -> have no nucleus, some RNA fragments, enter circulation via capillaries as RBCs or erythrocytes (in times of stress)

~2 days to from stem cell to reticulocyte
~2 days to mature to RBC

Question 6

Erythrocyte DESTRUCTION (apoptosis)?

Answer 6

100-120 day lifespan
Phagocytosis by spleen + liver
Haem -> bilirubin
Globin -> amino acids, Fe+ recyled

Question 7

Erythropoietin (EPO) production?

Answer 7

Peritubular interstitial cells of KIDNEY - 90%

Perisinusoidal cells of LIVER - 10%

Detection by peritubular capillaries @ JGA

Question 8

Erythropoietin (EPO) release factors?

Answer 8

In response to Low: Hb, O2, RBC

Rapidly produced/released (MINUTES) of stimulus. Max output @ 24hours (continues until stimulus removed.

Testosterone = increased EPO

Question 9

Erythropoietin (EPO) effect?

Answer 9

Increases pro-erythrocyte production (from stem cells) @ bone marrow.

Accelerates differentiation of progenitor cells and maturation time.

EPO SPEEDS SYNTHESIS OF RBCs!

Question 10

Gastroferrin?

Answer 10

Transports Fe2+ in the GIT.

Question 11

Serum iron?

Answer 11

Iron (Fe2+)
TIBC (total iron binding capacity)
How much iron is in the blood!

Question 12

Transferrin?

Answer 12

Plasma protein that binds and transports Fe2+ in circulating blood.

“Trucks that carry the iron”

Question 13

Transferrin saturation?

Answer 13

Fe2+ / TIBC

Question 14

Ferrritin?

Answer 14

Stores of Fe2+.

Mostly in cells (entercytes, macrophages).

Small amount blood.

Question 15

Ferroportin?

Answer 15

Transporter of iron out of cell.

Question 16

Hepcidin?

Answer 16

Regulator of ferroportin by (increased hepcidin = decreased ferroportin transport).

Chronic disease / cytokines stimulate increased release of hepcidin (not good).

Ferritin trapped in cells!

Question 17

3 classifications of anaemia?

Answer 17

1. Microcytic hypochromic (MCV<80fL)
2. Normocytic normochromic (MCV 80-94fL)
3. Macrocytic (MCV>94fL)

Question 18

B12 / Folate deficiency?

Answer 18

Macrocytic anaemia.
Inhibits DNA synthesis and cell division - cells keep growing!
Cells: large, immature, Hb-poor.

Reduced activity of METHIONINE SYNTHASE (vit B12) inhibits the regeneration of TETRAHYDROFOLATE (folate) in DNA synthesis.

Question 19

Compensatory mechanisms of chronic anaemia?

Answer 19

1. Increased 2,3 DPG…
2. Increased EPO…
3. Increased cardiovascular…(HR, RR, shunting to vital organs)

Question 20

MCV?

Answer 20

Mean cell volume (fL)

(measures cell size)

80-100fL: normocytic
<80fL: microcytic
>100fL: macrocytic

Question 21

MCH?

Answer 21

Mean cell haemoglobin (pg)

(Average mass of Hb per RBC)
(Responsible for colour)

30-34pg: normochromic
<30pg: hypochromic

Question 22

MCHC?

Answer 22

Mean cell haemoglobin concentration

Gives bigger picture

Question 23

Reticulocyte count?

Answer 23

Measure of erythrocyte production.

Decreased = problem @ marrow.

Increased = response to problem with RBCs (eg haemolysis) in circulation

Question 24

Reasons for MICROCYTIC hypochromic anaemia?

Answer 24

Low Fe2+

1. ACD
2. Fe2+ deficiency

Normal Fe2+

3. Siderblastic (problem haem synthesis)
4. Thalassaemia (problem Globin synthesis)
5. Lead poisoning

Question 25

Reasons for NORMOCYTIC normochromic anaemia?

Answer 25

Low/normal reticulocytes:

1. Renal disease
2. Bone marrow problem (eg stem cell defect)

HIGH reticulocytes:

3. Haemolysis
4. Haemorrhage
5. Splenomegally = increased phagocytosis

Question 26

Haemolysis causes?

Answer 26

Hereditary / Intracorpuscular:

1. G6PD deficiency
2. Sickle cell

Acquired / Extracorpuscular:

3. Auto-immune (pregnancy)
4. Allo-immune (transfusion)
5. Medications (eg Methyldopa)

Question 27

Reasons for MACROCYTIC anaemia?

Answer 27

Megloblastic:
1. Vitamin B12 and Folate deficiency!

Non-megloblastic:

2. Liver disease
3. Alcoholism
4. Hypothyroidism (endocrine problem)
5. Aplastic / hypoplastic

Question 28

Thalassaemia (alpha)?

Answer 28

Chromosome 16 - deletion

Loss of 4 alpha-globin genes = not compatible with life (HYDROPS FETALIS)

Loss of 3 alpha-globin genes = Hb H disease; mod-severe anaemia; slpenomegally

Loss 1 or 2 alpha-globin genes = silent carrier; usually asymptomatic / no anaemia

Question 29

Beta-Thalassaemia?

Answer 29

Chromosome 11 - mutation

Beta-Thalassaemia MINOR:
Single gene defect, mild anaemia, symptomless

Beta-Thalassaemia MAJOR:

• Severe anaemia @ 3-6 mo post birth
• hepatomegaly
• splenomegaly
• facies (bone expansion, marrow hyperplasia)
• regular blood transfusions: Fe2+ overload, chelation

Question 30

RCDW?

Answer 30

Red cell distribution width.

Normal: 11.5 - 14.5%

Indicates reason for anaemia - low or high variation.