4: Macrocytosis and macrocytic anaemia

Question 1

What is macrocytic anaemia?

Answer 1

Reduction in red blood cell number in which the red blood cells are larger than normal

Question 2

In macrocytic anaemia, haemoglobin is (high / low) and MCV is (high / low).

Answer 2

Hb low

MCV high (> 100 fL)

Question 3

What is macrocytosis?

Answer 3

Increase in red blood cell size

NOT the same as macrocytic anaemia (Hb and red cell count normal)

Question 4

Normal ranges for MCV vary from hospital to hospital.

On a blood film, what can red blood cells be compared with to say whether or not they are macrocytic?

Answer 4

Nucleus of a lymphocyte

because they tend to be larger than an RBC should be

Question 5

What values of MCV are

a) normal
b) indicative of macrocytosis?

Answer 5

a) 80 - 100 fL

b) > 100 fL

Question 6

Where are red blood cell precursors found?

Answer 6

Bone marrow

Question 7

Before reticulocytes, what are precursor red blood cells called?

Do they have a nucleus?

Answer 7

Erythroblast

Yes

Question 8

What do precursors to red blood cells accumulate as they divide?

Answer 8

Hb

Question 9

Red blood cell precursors get (bigger / smaller) as they divide.

Answer 9

smaller

Question 10

Where are reticulocytes found?

Answer 10

Circulation

Question 11

What do reticulocytes lose before becoming mature RBCs?

Answer 11

RNA

Question 12

What is a megaloblast?

Answer 12

Big erythroblast (precursor RBC) with abnormal nucleus

Question 13

What happens to

a) Hb synthesis
b) DNA synthesis and nuclear maturation
c) RNA synthesis

in a megaloblast?

Answer 13

a) Normal

b) Abnormal

c) Normal

i.e this is a problem with the DNA / nucleus, which remember causes a macrocytic anaemia

Question 14

What does a megaloblast turn into when it differentiates?

Answer 14

Macrocyte

Due to nuclear problem, most of the cells have undergone apoptosis, so cell count is reduced (macrocytic anaemia)

Question 15

What is the main causes of megaloblastic (a type of macrocytic) anaemia?

Answer 15

Vit B12 / Folic acid deficiency

Question 16

Why do Vit B12 and folic acid deficiencies cause megaloblastic anaemia?

Answer 16

Both involved in DNA synthesis and nuclear maturation

Question 17

What genetic process are Vit B12 and folic acid involved in?

Answer 17

Gene silencing

Question 18

Which vitamin is carried to the distal ileum by intrinsic factor?

Answer 18

Vit B12

Question 19

Which protein carries Vitamin B12 to the duodenum before it is bound to intrinsic factor?

Answer 19

R protein

Question 20

In which foods is Vitamin B12 found?

Answer 20

Animal products

Red & white meat, fish, eggs, cow’s milk

Question 21

Who is prone to Vitamin B12 deficiency?

Answer 21

People who don’t eat animal products

People on PPIs (inadequate stomach acid to liberate Vit B12 from food)

People at risk of malabsorption (overgrowth, surgical resection)

Alcoholics (indaequate nutrition)

Question 22

Which stomach cells produce intrinsic factor?

Answer 22

Parietal cells

Question 23

In which autoimmune disease are gastric parietal cells destroyed?

Answer 23

Pernicious anaemia

Causes Vit B12 deficiency

Question 24

Who is prone to folate deficiency?

Answer 24

Alcoholics (inadequate nutrition)

Question 25

What are the general symptoms of anaemia?

Answer 25

**Pallor** **Fatigue** **Difficulty concentrating** **Dizziness** **Shortness of breath**

Question 26

What are specific symptoms of **Vit B12 / folic acid deficiency**?

Answer 26

**GI problems** - weight loss, diarrhoea, jaundice etc. - suggest a primary GI cause **Glossitis** (sore tongue) **Delayed development**

Question 27

What irreversible neurological changes are caused by Vit B12 deficiency?

Answer 27

**Delayed degeneration of dorsal columns** (spinothalamic tract) **Dementia** NOT the same as the B1 encephalopathy

Question 28

What are **blood film findings** specific to **macrocytic anaemia** caused by **Vit B12 / folate deficiency?**

Answer 28

**Macrovalocytes** **Hypersegmented neutrophils**

Question 29

How is **megaloblastic anaemia** treated?

Answer 29

**Treat underlying cause** e.g diet, malabsorption **Vit B12 injections** in pernicious anaemia **Folic acid supplements**

Question 30

What are some causes of isolated **macrocytosis**?

Answer 30

**Alcohol** **Liver disease** **Hypothyroidism**

Question 31

What **bone marrow response to blood loss** can cause a false macrocytosis?

Answer 31

**Reticulocytosis** because reticulocytosis are immature RBCs and naturally bigger

Question 32

What are **cold agglutinins?** What false reading do they cause?

Answer 32

Proteins which stick RBCs together in clumps False macrocytosis

Question 33

Why do patients with pernicious anaemia appear jaundiced?

Answer 33

**Vit B12 / Folate deficient** **MCV increases** (macrocytosis) **RBCs can't pass into the circulation and die in the bone marrow** (ineffective erythropoiesis) **Hb broken down into bilirubin** \> jaundice

Question 34

What does **MCV** mean? What unit is it measured in?

Answer 34

**Mean cell volume** **Femtolitres**

Question 35

What is the normal range of MCV in femtolitres?

Answer 35

**80 - 100 fL** ranges vary slightly

Question 36

Which value and above of MCV is abnormal?

Answer 36

**\> 100 fL** ish compare the red blood cell size to the nucleus of a lymphocyte - bigger is abnormal

Question 37

From which **dietary sources** is a) **vitamin B12** b) **folate** obtained?

Answer 37

**a) Animal products** **b) Leafy veg, liver, fortified cereals**

Question 38

How long do **folate** **stores** last?

Answer 38

**4 months**

Question 39

How long do **vitamin B12** stores last?

Answer 39

**2 - 4 years**

Question 40

What is a **hypersegmented neutrophil**?

Answer 40

**Neutrophil with nucleus containing 6+ lobes**