Introduction to Anaemia and Microcytic Anaemias

Question 1

Definition of anaemia

Answer 1

Reduced total red cell mass

Question 2

What are the surrogate markers for anaemia?

Answer 2

Haemoglobin

Haematocrit

Question 3

What are the normal Hb ranges?

Answer 3

Adult males
Hb <130g/L
Hct 0.38-0.52

Adult females
Hb <120g/L
Hct 0.37-0.47

Question 4

How is Hb measured by spectophotometry?

Answer 4

1. lyse the red cells to create Hb solution
2. Stabilise Hb molecules using Cyan-metHb
3. Measure the optical density (OD) at 540nm
4. OD Proportional to the concentration (Beer’s Law)
5. Hb concentration calculated against known reference standard cyan-metHb concentration solution

Question 5

Name the physiological response to anaemia with a functional bone marrow

Answer 5

Reticulocytosis - increased red cell production

This response takes a few days

Question 6

What are reticulocytes?

Answer 6

Immature RBC
Larger than average RBC
Still have RNA remnants

Question 7

Why does reticulocytes appear purple/deep red on staining?

Answer 7

Presence of RNA remnants

Question 8

Describe the appearance of blood film with reticulocytes

Answer 8

Polychromatic

Question 9

List the measured red cell indices

Answer 9

Hb concentration
Number of red cells (conc.)
Size of red cells - MCV

Question 10

List the calculated indices

Answer 10

Haematocrit
Mean cell Hb
Mean cell Hb concentration

Question 11

What are the pathophysiological classifications of anaemia?

Answer 11

a) decreased production (low retic count as not producing red cells)
b) Increased loss or destruction (high retic count as BM normal)

Question 12

List the types of anaemia due to decreased production

Answer 12

a) Hypoproliferative - reduced AMOUNT of erythropoeisis

b) Maturation abnormality - erythropoeisis present but INEFFECTIVE
i. Cytoplasmic defects: impaired haemoglobinisation
ii. Nuclear defect - impaired cell division

Question 13

List the causes of anaemia due to destruction of red cells

Answer 13

bleeding

Haemolysis

Question 14

How to interpret MCV

Answer 14

Low - microcytic - problem with hemoglobinisation

High - macrocytic - problem with maturation

Question 15

Where in the cell is Hb synthesised?

Answer 15

Cytoplasm

Question 16

What are the morphological features of red cells in anaemia due to deficient Hb synthesis?

Answer 16

Microcytic (small)

Hypo-chromic (lacking in colour

Question 17

Shortage of which components leads to microcytic, hypochromic anaemia (low Hb)?

Answer 17

Globin

Haem (porphyrin ring, Fe2+)

Question 18

What are the two BROAD causes of hypochromic, microcytic anaemias?

Answer 18

Haem deficiency

Globin deficiency

Question 19

List the causes of haem deficiencies

Answer 19

Lack of iron for erythropoiesis

Problems with porphyrin synthesis (extremely rare) - lead poisoning, pyridoxine responsive anaemia

Congenital sideroblastic anemia

Question 20

List the causes of globin deficiency

Answer 20

Thalassemia

Question 21

Which molecule is circulating iron bound to?

Answer 21

Transferrin

Question 22

What is the role of macrophages in iron metabolism

Answer 22

Iron is transferred to bone marrow macrophages which feed it to the red cell precursor

Question 23

Where is iron stored in ferritin?

Answer 23

liver

Question 24

Which test assesses functional iron?

Answer 24

Haemoglobin

Question 25

Which test assesses transported iron?

Answer 25

Serum iron Trasnferrin Transferrin saturation

Question 26

Which test assesses storage iron?

Answer 26

Serum ferritin

Question 27

Describe structure and function of transferrin

Answer 27

Protein with two binding sites fro iron atoms Transfers iron from donor tissues (macrophages, intestinal cells, hepatocytes) to tissues expressing transferrin receptors (especially erythroid marrow)

Question 28

Which test measures iron supply?

Answer 28

% saturation of transferrin with iron

Question 29

In which scenarios will transferrin be increased and reduced?

Answer 29

Iron deficiency anemia - reduced Anemia of chronic disease - reduced Genetic haemochromatosis - increased

Question 30

What is the significance of ferritin levels?

Answer 30

Reflects intracellular ferritin synthesis in response to iron status of the host INDIRECT measure of storage iron NOTE: ferritin is also an acute phase reactive protein and thus may not be an accurate representation of iron stores

Question 31

Which parameters confirm iron deficiency?

Answer 31

combination of anaemia (decreased functional iron) and reduced storage iron (low serum ferritin)

Question 32

List the causes of iron deficiency

Answer 32

1. Insufficient intake to meet physiologic requirement a) relative - children and pregnant women b) absolute - vegetarian diet 2. Malabsorption - chron's, coeliac, achlorhydria 3. Blood loss - menorrhagia, GI (tumours, ulcers, NSAIDS), hematuria

Question 33

What are the sequential consequences of negative iron balance?

Answer 33

1. Exhaustion of iron stores 2. Iron deficient erythropoiesis (falling red cell MCV) 3. Microcytic anemia 4. Epithelial changes - skin, koilonychia