Introduction to Anaemia and Microcytic Anaemia

Question 1

Define anaemia?

Answer 1

Reduced total red cell mass

Question 2

Measuring total red cell mass?

Answer 2

Hb conc. is a surrogate marker, as red cell mass is difficult to measure

Other markers include haematocrit

Question 3

Hb levels in anaemia?

Answer 3

Adult males <130 g/l

Adult females <120 g/l

Question 4

Hct levels in anaemia?

Answer 4

Adult males 0.38-0.52

Adult females 0.37-0.47

Question 5

Where does red cell production occur?

Answer 5

In the bone marrow, several erythroid precursors cluster around a central ‘nursing’ histiocyte (tissue macrophage) i.e: the tissue macrophage

Question 6

What is the Hct?

Answer 6

Ratio (or commonly expressed as a %) of the whole blood that is red cells, if the sample is left to settle

NOTE - now, it is calculated by adding the calculated volume of the rbcs it counts

Question 7

Situations where Hct is not a good marker of anaemia?

Answer 7

Rare, e.g: acute blood loss; in this case, the anaemia would only be noticed if fluids were given, as this would cause plasma dilution (haemodilution effect)

NOTE - this explains why minor anaemias can occur when giving fluids

Question 8

How do reticulocytes respond to anaemia?

Answer 8

Increased rbc production (RETICULOCYTOSIS)

Up-regulation of reticulocyte production by the bone marrow, in response to anaemia, takes a few days

Question 9

What are reticulocytes?

Answer 9

Rbcs that have just left the bone marrow

Question 10

Structure of reticulocytes?

Answer 10

Larger than mature rbcs and retain some RNA, resulting in the purple/deeper red stain; the blood film appears POLYCHROMATIC, i.e: >1 colour

NOTE - polychromatic indicates reticulocytes

Question 11

Measured and calculated red cell indices?

Answer 11

Measured:

• Hb conc.
• No. of rbcs (conc.)
• Size of the rbcs (Mean Cell Volume, MCV)

Calculated:

• Hct
• Mean cell Hb
• Mean cell Hb conc. - an internal lab check to ensure that the measured values above are correct; otherwise, it is unimportant

Question 12

Other methods of assessing rbcs?

Answer 12

Blood film - for cellular morphology

Reticulocyte count - assess marrow response to anaemia Others

Question 13

Broadly, how are anaemias classified?

Answer 13

Pathophysiological classification of anaemia

OR

Morphology (based on cell size and Hb content)

Question 14

Patholophysiological classification of anaemia?

Answer 14

Decreased production - if this is the case, the reticulocyte count will be low

• Hypoproliferative - reduced AMOUNT of erythropoiesis
• Maturation abnormality - erythropoiesis is present but ineffective; 2 types are cytoplasmic defects, with impaired haemoglobinisation, and nuclear defects, with impaired cell division

Increased loss/destruction of rbcs - if this is the case, the reticulocyte count will be high

• Bleeding
• Haemolysis

Question 15

How can cytoplasmic and nuclear defects be distinguished (maturation abnormalities)?

Answer 15

If MCV is low (microcytic anaemia), consider impaired haemoglobinisation (cytoplasmic defects)

If MCV is high (macrocytic anaemia), consider problems with maturation

Question 16

Describe haemoglobinisation

Answer 16

Hb synthesis occurs in the cytoplasm, using globins and haem

NOTE - haem synthesis requires Fe2+ (ferrous) and a porphyrin ring

Defects result in small rbcs with a low Hb content, i.e: microcytic (small) cells that are hypochromic (lack colour)

Question 17

In other words, why does a hypochromic, microcytic anaemia occur?

Answer 17

Deficiency Hb synthesis, i.e: cytoplasmic defect

Question 18

2 broad causes of hypochromic microcytic anaemias?

Answer 18

Haem deficiency

Globin deficiency

Question 19

Causes of haem deficiency?

Answer 19

Lack of iron for erythropoiesis:

• IRON DEFICIENCY (low body iron)
• Anaemia of chronic disease (normal body iron but a lack of available iron)

NOTE - most patients with chronic disease do not have this

Problems with porphyrin synthesis (very rare):

• Lead poisoning
• Pyridoxine responsive anaemia - patients are deficient in pyridoxine and respond to it if supplemented

Question 20

Causes of globin deficiency?

Answer 20

Thalassaemia (trait, intermedia, major) - rare in the UK but common in other parts of the world

Question 21

States of iron?

Answer 21

Fe2+ (ferrous)

Fe3+ (ferric)

Question 22

Functions of iron?

Answer 22

O2 transport - in Hb and myoglobin

Electron transport - mitochondrial production of ATP

Question 23

Problems assoc. with iron?

Answer 23

Potentially toxic, as it generates free radicals (ROS)

Question 24

Iron exchange pathway?

Answer 24

A closed system

Only a small amount of iron is absorbed and lost per days (1 mg/day)

A small amount is present in the plasma; most is present in the red cell Hb, liver stores, macrophage, erythroid marrow

Circulating iron is transferred to bone marrow macrophages and ‘fed’ to rbc precursors

NOTE - most of the iron is in Hb; it is stored as ferritin (for Fe3+ ions) in the liver stores

Question 25

How does iron circulate?

Answer 25

Bound to transferrin

Question 26

Tests used to asses iron status?

Answer 26

Funtional iron - Hb Transported iron (tests of iron availability): * Serum iron * Transferrin * Transferrin saturation Storage iron: • Serum ferritin

Question 27

Structure of transferrin?

Answer 27

Protein with 2 binding sites for iron

Question 28

Function of transferrin?

Answer 28

Transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (esp. erythroid marrow)

Question 29

How is the iron supply measured?

Answer 29

% saturation of transferrin This is reduced in iron deficiency and anaemia of chronic disease It is increased in genetic haemochromatosis

Question 30

What is ferritin?

Answer 30

Large IC protein, storing up to 4000 ferric ions A small amount of ferritin is present in serum and this reflects IC ferritin synthesis in response to the iron status of the host

Question 31

Direct measure of storage iron?

Answer 31

Serum ferritin (easily measured) NOTE - low ferritin = iron deficiency

Question 32

How can iron deficiency be confirmed?

Answer 32

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

Question 33

Causes of iron deficiency?

Answer 33

Dietary insufficiency - in general, this is unlikely in men: * Relative - esp. in women of child-bearing age and in children * Absolute - sometimes with vegetarian diets Losing iron - blood loss (usually GI) Lack of absorption (malabsorption): * Coeliac disease * Achlorhydria (patients on PPIs) NOTE - identifying iron deficiency is not enough; must identify why

Question 34

Causes of chronic blood loss?

Answer 34

Menorrhagia GI, e.g: tumours, ulcers, NSAIDs Haematuria

Question 35

Iron status with menstrual blood loss?

Answer 35

Precarious, as an average of 15-20 mg/month is lost (with heavy menstrual blood loss, this is \>30 mg/month) Average daily intake is only 1 mg/day

Question 36

Sequential consequences of negative iron balance?

Answer 36

1. Exhaustion of iron stores 2. Iron deficiency erythropoiesis (falling red cell MCV) 3. Microcytic anaemia 4. Epithelial changes (late), e.g: skin changes, koilonychia

Question 37

Common cause of occult blood loss?

Answer 37

Small volume of GI blood loss can occur without any symptoms/signs of bleeding This can outstrip maximal dietary absorption of iron and result in anaemia Iron absorption can be increased by iron supplements

Question 38

Treatment of iron deficiency anaemia?

Answer 38

Iron replacement therapy relieves the iron deficiency anaemia but DOES NOT treat the underlying cause Ix of underlying cause is essential