Microcytic and macrocytic anaemia

Question 1

What is the definition of anaemia?

Answer 1

A reduction of Haemoglobin concentration of the blood below the normal range for age and sex.

Question 2

What are the male and female refence ranges for anaemia?

Answer 2

• Male - 13.3-16.7 g/dL
• Female – 11.8 – 14.8 g/dL

Question 3

What are thee general signs and symptoms of anaemia?

Answer 3

Pallor of the conjunctival mucosa (a) and of the nail bed (b) Retinal haemorrhages (c) caused by severe anaemia.

Question 4

What are the normal values for blood cells and haematinics?

Answer 4

Question 5

What does leukocyte and platelet counts help distinguish between?

Answer 5

Pure anaemia and ‘pancytopenia’

Question 6

A high reticulocyte count is indicative of

Answer 6

anaemia

Question 7

What are the indicators of microcytic, hypochromic anaemia?

Answer 7

• MCV<80FL, MCH <27 pg
• Iron deficiency Thalassaemia
• Lead poisoning

Question 8

What are the indicators of normocytic, normochromic anaemia?

Answer 8

• MCV 80-95fl, MCH> 27pg
• Haemolytic anaemia
• Chronic anaemia
• Renal disease

Question 9

What are the indicators of macrocytic anemia?

Answer 9

• MCV>95fl
• Vitamin B₁₂ or folate deficiency

Question 10

What is examination is essential in all cases of anaemia?

Answer 10

Blood film examination

Question 11

What may reveal different anaemia’s?

Answer 11

Abnormal red cell size (anisocytosis) and shape (poikilocytosis)

Question 12

What are the causes of red cell abnormalities?

Answer 12

Question 13

What red cell inclusions may be seen in the peripheral blood film in various conditions?

Answer 13

Question 14

What are the causes of microcytic anaemia?

Answer 14

Question 15

What are the features of iron deficiency anaemia?

Answer 15

Question 16

Iron is provided by dietary sources such as

Answer 16

liver, meat, sea foods, eggs, vegetables and dried foods.

•May present a problem in food absorption

Question 17

How much iron do people need?

Answer 17

Question 18

What is microcytic, hypochromic anaemia?

Answer 18

• Disorder of haem eg iron deficiency or malignancy
• Disorder in synthesis of globin eg thalassemia

Question 19

Give a summary of iron cycling in a healthy individual

Answer 19

Question 20

Describe iron uptake, storage and utilization for Hb synthesis

Answer 20

Question 21

When the rate of iron absorption from diet is low, the body uses iron in stores causing

Answer 21

a negative balance

Question 22

Stores become depleted =

Answer 22

latent deficiency

Question 23

What are the causes of depletion of iron level stores

Answer 23

Causes:

1. Increased requirement (bleed/pregnancy/puberty)
2. Decreased supply of iron

Question 24

Compare latent iron deficiency and iron deficiency anaemia

Answer 24

Question 25

What are the laboratory findings in iron deficiency anaemia?

Answer 25

**_FBC and Blood film_** **Low Hb, Red Cell count, MCH, MCV** 1. Microcytosis= small red blood cells 2. Hypochromia= pale red blood cells 3. Elliptocytosis= long thin cells 4. Tear drop poikilocytes= tear shaped cells 5. Anisocytosis= red blood cells are unequal in size **Anaemia is Microcytic and Hypochromic** Can also investigate Serum Ferritin – main storage protein of iron –Remember! (Acute phase protein)

Question 26

What laboratory findings indicate microcytic and hypochromic anaemia

Answer 26

**Microcytic and hypochromic** * Smaller cells * Large centre of pallor * Low HB * Pencil cells –classic finding of IDA

Question 27

What would you see on a normal blood film?

Answer 27

* Normal RBC's. * Uniform * More pigmented * Zone of central pallor about 1/3 the size of the RBC

Question 28

What are the treatments for anaemia?

Answer 28

* Iron supplements * The most commonly prescribed supplement is **ferrous sulphate** twice daily * **In severe cases** - blood transfusion & iron therapy * Vitamin C * Birth control pills

Question 29

Show a d**imorphic blood film** in IDA responding to iron therapy

Answer 29

2 population of RBCs present; microcytic and hypochromic and the other normocytic and well haemaglobinised

Question 30

What is macrocytic anaemia?

Answer 30

* RBCs are abnormally large (MCV \>98fL) * Many causes but can be subdivided into **megaloblastic** and non-megaloblastic anaemia * Based on the appearance of developing erythroblasts in the bone marrow

Question 31

What are the causes of macrocytic anaemia?

Answer 31

Question 32

What are the sources of B12 (cobalamin)

Answer 32

**Food source** **Vitamin B₁₂ content (μg)** Beef liver, 3.5 oz ⇢48 Rainbow trout, wild, 3.0 oz ⇢5.4 Salmon, 3.0 oz ⇢4.9 Beef, 3.0 oz ⇢2.4 Tuna, white, 3.0 oz ⇢1.0 Yogurt, plain, 1 cup ⇢1.4 Fortified cereal ⇢6.0 Milk, 1 cup ⇢0.9 Swiss cheese, 1 oz ⇢0.9 Egg, 1 whole ⇢0.6

Question 33

What is the RDA for B12

Answer 33

**2.4 μg**

Question 34

How is B12 synthesised and where is it found in the body?

Answer 34

* **Synthesized** exclusively by microorganisms * Found in the liver of animals bound to protein known as **methycobalamin** * To be absorbed the vitamin B12 present in foodstuffs must be liberated and extracted by the combination of the proteolytic enzyme pepsin and the acid environment of the stomach THIS TYPE OF ANAEMIA AFFECTS VEGETARIANS

Question 35

**Vitamin B12 is an essential cofactor of 2 enzymes:**

Answer 35

a) Conversion of L-methylmalonyl co-enzyme A to succinyl co-enzyme A b) Methylation of homocysteine to methionine

Question 36

Give a summary of B12 absorption

Answer 36

1. B12 complexes with **intrinsic factor (IF)** 1:1 2. Intrinsic factor (IF) acts as a carrier protein by delivering B12 to the Large intestine where it can be absorbed by the ileum 3. For absorption to occur, docks to receptor on an enterocyte (**cubulin, megalin and amnionless)** 4. Directs endocytosis of the IF-B₁₂ complex in the distal ileum where **B₁₂ is absorbed** and i**ntrinsic factor** is destroyed

Question 37

Describe B12 transport

Answer 37

Transcobalamin and Haptocorrin

Question 38

What are the 2 main causes of vitamin B12 deficiency?

Answer 38

1.**Malnutrition** Inadequate dietary intake– vegan diet- **uncommon** **2. Malabsorption** –**90% of cases** **lack of intrinsic factor** – Pernicious Anaemia. –Gastrointestinal disease–Surgical removal on site of IF synthesis –Drug Induced –Increased requirement of vitamin- pregnancy

Question 39

What is pernicious anaemia

Answer 39

* Immune system attacks the cells in the stomach that produce the intrinsic factor, which means body in unable to absorb vitamin B12 * Usual onset 60 years * *Helicobacter pylori* infection may initiate an autoimmune gastritis which presents in younger individuals as iron deficiency and in elderly as pernicious anaemia * 1:10,000 in northern Europe••Treated with B12 injections

Question 40

Describe the lab diagnosis of B12 deficiency

Answer 40

Question 41

What are the sources of folate?

Answer 41

Question 42

Folate vs vitamin B12

Answer 42

Question 43

What are the causes of folate deficiency?

Answer 43

1. **Inadequate dietary intake** (common), folate is **heat labile**. 2. **Intestinal malabsorption** Coeliac disease- destruction of intestinal villi= malabsorption of folate **3. Increased requirement** Pregnancy 4. **Drug induced** interferes with absorption or metabolism Alcohol (coupled with poor diet) **Methotrexate** 1. inhibits dihydrofolate reductase= decreased supply of folates 2. .Folate aids those treated with long-term, low-dose methotrexate for rheumatoid arthritis (RA) or psoriasis

Question 44

Why are large cells produced in macrocytic anaemia?

Answer 44

* Folate necessary for nucleotides (AMP/GMP) * Retardation of DNA synthesis * Inhibition of **rate limiting step**

Question 45

Folate function

Answer 45

Question 45

Folate necessary for

Answer 45

Question 46

Biochemical basis of megaloblastic anaemia

Answer 46

* •Inadequate amounts of (**dUMP**)/ (**dTMP**) leads to a failure of DNA synthesis •Loss of nucleus in cells with fewer cell divisions leads to larger cells

Question 47

megaloblastic anaemia: FBC and Blood Film

Answer 47

**Reduced Hb,** **increased MCV (\>100)** **MCH= (HYPERCHROMIC)** **Macrocytosis**= decreased number of cell divisions before loss of nucleus of the cell and release into the circulation * **Megaloblasts** * **Poikilocytes** * **anisocytosis** **Hypersegmented neutrophils-** 7-8 lobes instead of 2-5 lobes= DNA defect & structural abnormalities in nuclear chromatin Low levels of serum B12 Low levels of serum and red cell folate Presence of autoantibodies to intrinsic factor/gastric parietal cells- Pernicious anaemia

Question 48

Closer look at macrocytic blood film

Answer 48

Question 49

Macrocytic anaemia diagnosis

Answer 49