5 - Red cells and Anaemia

Question 1

Buffy coat

Answer 1

Leukocytes & platelets (<1% of total blood)

Question 2

Red blood cells

Answer 2

• Made in bone marrow
• Small anuclear flexible biconcave disc shaped cells
• Most numerous cell in blood
• Generates energy through glycolytic pathway

Question 3

How long do red blood cells last

Answer 3

120 days

Question 4

Haem and globin

Answer 4

• Haem: Mitochondria, contains iron
• Globin: 4 polypeptide chains

Question 5

Defects in globin

Answer 5

Thalassaemia and sickle cell disease

Question 6

Blood cell production

Answer 6

Haemopoiesis

Question 7

RBC production

Answer 7

Erythropoiesis

Question 8

Erythropoiesis

Answer 8

Production of RBCs under influence of erythropoietin (EPO, produced in kidney)

Question 9

Stages of RBC development in bone marrow

Answer 9

• Cell becomes smaller
• Nucleus matures (chromatin condensation)
• Cytoplasm gains haemoglobin
• Nucleus is extruded to produce mature RBC
• Newly formed RBC = reticulocyte
• RNA lost to become mature RBC

Question 10

Erythropoietin (EPO)

Answer 10

• Hormone that regulates red blood cell production
• Produced in kidney
• Stimulated by renal O2 tension caused by anaemia, low atmospheric O2, defective cardiac or pulmonary function

Question 11

Requirements for erythropoiesis

Answer 11

• Erythropoietin (EPO)
• Metals (iron, cobalt)
• Vitamins (B12, folate)
• Amino acids
• Other cytokines (IL3)

Question 12

Iron

Answer 12

• Only 5-10% of iron intake is absorbed
• Binds in transferrin
• Require 1-2mg / day
• Excess stored in macrophages

Question 13

Iron metabolism pathway

Answer 13

Duodenum and jejunum –> binds to transferrin –> bone marrow –> circulating haemoglobin –> Macrophages, liver, muscle myoepithelium

Question 14

Vitamin B12 (Cobalamin)

Answer 14

• Required for nuclear maturation
• Dietary B12 combines with intrinsic factor (stomach)
• IF-B12 complex attaches to receptors in ileum
• Absorbed B12 binds to Transcobalamin II
• B12 carried to marrow and liver

Question 15

Where does B12 come from

Answer 15

Meat, eggs, milk

Question 16

Where does folate come from

Answer 16

Fruit and vegetables

Question 17

Folate

Answer 17

• Required for nuclear maturation
• Absorbed in upper small intestine
• Small body stores (3-4 months)
• Deficiencies result in anaemia (macrocytic)

Question 18

Red Blood Cell Membrane

Answer 18

• Deformable & stabile (navigate small vessels)
• Lipid bilayer with embedded proteins
• Proteins for membrane elasticity
• Proteins are embedded with lipids

Question 19

How do RBCs die

Answer 19

• Removed in reticulo-endothelial system
• Iron released and stored as ferritin
• Globin chains are degraded to amino acids and returned to body pool
• Haem broken down to bilirubin and excreted by liver

Question 20

Normal lifespan of RBcs

Answer 20

120 days

Question 21

Haemolysis

Answer 21

Reduced RBc lifespan/increased rate of RBC destruction

Question 22

Anaemia

Answer 22

A reduction in haemoglobin concentration below
normal range for age and gender of the individual

Question 23

Is anaemia a disease

Answer 23

No but rather a manifestation of another disease

Question 24

Clinical features of anaemia

Answer 24

• Paleness
• Lethargy
• Shortness of breath
• Tachycardia
• Fainting
• Low BP

Question 25

Causes of anaemia

Answer 25

- Reduced bone marrow production of red cells - Increased blood loss (haemorrhage) - Increased RBC destruction (haemolysis)

Question 26

Primary causes of anaemia

Answer 26

Bone marrow failure

Question 27

Secondary causes of anaemia

Answer 27

Underlying problem reducing ability of the marrow to make red blood cells

Question 28

Primary causes of reduced bone marrow production of red cells leading to anaemia

Answer 28

- Bone marrow failure (aplastic anaemia) - Red cell aplasia - Bone marrow dysfunction (myelodysplasia)

Question 29

Secondary causes of reduced bone marrow production of red cells leading to anaemia

Answer 29

- Insufficient nutrients (iron, folate, B12, Erythropoietin) - Infection - Drugs - Marrow infiltration (Leukaemia, cancer)

Question 30

Iron deficiency causes

Answer 30

- Poor iron intake / dietary deficiency - Poor iron absorption / malabsorption - Chronic blood loss: - Increased demand / iron utilisation

Question 31

B12 deficiency causes

Answer 31

poor absorption (pernicious anaemia)

Question 32

Folate deficiency

Answer 32

Poor diet, increased demands

Question 33

Megaloblastic anaemia

Answer 33

- Caused by B-12 and folate deficiency - Larger cells with delay in development of nucleus

Question 34

Causes of haemorrhage leading to anaemia

Answer 34

- Acute (Accident, injury, surgery) - Chronic (Malignancy, inherited platelet or bleeding disorder)

Question 35

Causes of increased RBC destruction leading to anaemia

Answer 35

- Hereditary: Inherited defect of red cell membrane, red cell enzymes or globin chains - Acquired: sepsis, microorganisms, liver or kidney disease, fragmentation haemolysis

Question 36

Hereditary spherocytosis

Answer 36

- Common cause of inherited anaemia - Defect of RBC membrane proteins - RBCs more rigid than normal - RBCs lack central pallor (spherocytes)

Question 37

Defect of RBC membrane proteins that causes hereditary spherocytosis

Answer 37

Structural proteins spectrin, actin and band 3

Question 38

Thalassaemia

Answer 38

Reduced production of a or b globin chains

Question 39

Structural haemoglobinopathies

Answer 39

Abnormal globin chain structure (e.g. sickle cell anaemia)

Question 40

Autoimmune haemolytic anaemia

Answer 40

An antibody directed against its own red blood cells. Caused by leukaemia and autoimmune diseases

Question 41

Haemolytic anaemia due to infections

Answer 41

- Severe bacterial sepsis (causes RBCs to fragment) - Malaria (Parasite inside red cell causes lysis) - Clostridium welchii (Auto-antibody like haemolysis)