Red cells 1 + 2 (ALSO SEE TABLE)

Question 1

Discuss the derivation of normal ranges for a FBC - DONE

Outline pathophysiological or morphological approaches to the assessment of anaemia - DONE

Describe symptoms of anaemia - DONE

Discuss investigations for iron deficiency anaemia

Answer 1

Outline structure of Hb and the basis of the haemoglobinopathies and thalassaemias - DONE

Describe breakdown of Hb to bilirubin and discuss the value of direct and indirect bilirubin measurement

Outline the principle and uses of the direct antiglobulin test in assessing haemolysis

Causes of inherited anaemias in terms of MEMBRANES, ENZYMES or Hb - DONE

Question 2

Define anaemia

Answer 2

Reduction in RBCs or their haemoglobin content

Question 3

Substances required for RBC production

• metals
• vitamins
• amino acids
• hormones

Answer 3

Metals - iron mainly
Vitamins - B12, folate (both mainly)
Hormones - erythropoietin mainly

Question 4

How is Hb broken down to bilirubin

Answer 4

By the reticuloendothelial system

• blood filtered through spleen and old RBCs broken down
• the haem component is processed in the liver into bilirubin
• the globin component (protein component) is broken down to amino acids which are reused

Question 5

Erythrocytes have 3 components

Answer 5

Membrane, which contains:
Enzymes
Haemoglobin

Question 6

What 2 proteins forming a chain in the cytoskeleton are important for maintaining the shape of RBCs

Answer 6

A & B-spectrin

Question 7

In congenital anaemias, genetic defects can be described of what 3 things

Answer 7

In red cell membrane
In metabolic pathways (Enzymes)
In haemoglobin

Question 8

What enzyme is involved in the pentose phosphate shunt and what is its relevance to RBCs

Answer 8

G6PD (glucose-6-phosphate dehydrogenase)
-responsible for 1st step in the pentose phosphate pathway which is a pathway important in preventing RBCs from oxidative damage

Question 9

Outline structure of Hb

Answer 9

Four polypeptide subunits

• Each subunit is composed of a protein component (GLOBIN chains) associated with a non-protein component (HAEM)
• 2 globin components are ALPHA chains and 2 are BETA chains

Question 10

Where is the haem component in associated with the globin component

Answer 10

Globin chain wraps around the haem group in the centre

Question 11

Binding affinity of oxygen to haemoglobin increased under what conditions (4)

Answer 11

Increased pH
Decreased [2,3-BPG]
Decreased temp
Decreased PCO2

Question 12

Adult haemoglobin (HbA) composed of what globulin chains

Answer 12

2 alpha and 2 beta (

Question 13

Foetal haemoglobin composed of what globulin chains

Answer 13

2 alpha and 2 gamma

Question 14

Define haemoglobinopathy + 2 causes of it

Answer 14

Inherited abnormalities of haemoglobin synthesis

Reduced or absent globin chain production, e.g. THALASSAEMIA
Mutations leading to structurally abnormal globin chain, e.g. SICKLE CELL DISEASE (HbS), HbC, HbD etc

Question 15

Sickle cell Hb composed of

Answer 15

Haem molecule and:
2 α chains
2 β (sickle) chains

Question 16

Missing both of which globulin chain would be INCOMPATIBLE WITH LIFE + why

Answer 16

Alpha chains

-because no way of making foetal Hb if no alpha chains

Question 17

Homozygous alpha zero thalassaemia is the clinical diagnosis of someone with no alpha chains

What death linked condition does this cause in babies

Answer 17

Hydrops foetalis

Question 18

How normal ranges of a FBC are derived

Answer 18

Subjects without disease
Normal distribution
Mean +/- 2 standard deviations
Excludes 5% of “normals”

Question 19

Factors influencing normal ranges of a FBC

Answer 19

Age
Sex
Ethnic origin
Time of day sample was taken

Question 20

Reference ranges of

• male Hb (12-70 & >70)
• female Hb (12-70 + >70)

Answer 20

Male

• 140-180g/l
• 116-156

Female

• 120-160
• 108-143

Question 21

Symptoms/signs of anaemia in general

Answer 21

Fatigue
Dyspnoea
Dizzy
Chest pain

Pallor
Oedema

Question 22

Underlying causes of anaemia

Answer 22

Bleeding

• menorrhagia
• GI bleeding

Malabsorption

• diarrhoea
• weight loss

Jaundice

Splenomegaly

Question 23

Pathophysiological approach to assessing anaemia

-firstly consider defect in 3 ways

Answer 23

Defect of

• bone marrow
• RBC itself
• destruction or loss

Question 24

Pathophysiological approach to assessing anaemia
-once you’ve considered the 3 ways of defect (BONE MARROW, RBC ITSELF, DESTRUCTION/LOSS), think of the problems that can arise from these areas

So in what ways can the above 3 things be affected?

Answer 24

Bone marrow

• cellularity
• stroma
• nutrients

RBC

• membrane
• enzymes
• Hb

Destruction/loss

• blood loss
• haemolysis
• hyperpslenism

Question 25

What are the 2 red cell indices (measurement of red cell size + Hb content) that can give a morphological description of anaemia (and a clue to the cause)

Answer 25

MCH (mean cell Hb) | MCV (mean cell volume)

Question 26

Morphological approach to assessing anaemia | -what are the 3 morphological subtypes that can be derived from the red cell indices from a FBC (MCH & MCV)?

Answer 26

Hypochromic microcytic -RBCs have low Hb & smaller + paler Normochromic normocytic Macrocytic -large RBCs that carry less Hb; also when RBCs grow too big, there's less of them

Question 27

Morphological approach to assessing anaemia -once you've derived the morphological cause (HYPOCHROMIC MICROCYTIC, NORMOCHROMIC NORMOCYTIC OR MACROCYTIC), what tests would you do for each cause respectively to further investigate?

Answer 27

Hypochromic mcirocytic -serum ferritin (as the cause is usually LOW IRON) Normochromic normocytic - reticulocyte count (gives idea bone marrow function) - blood film Macrocytic - B12/folate - bone marrow

Question 28

Majority of body's iron is where

Answer 28

Bound to Hb

Question 29

Iron is stored where in body in what form

Answer 29

Ferritin in liver

Question 30

What does hepcidin do + what is it made by

Answer 30

Regulates iron transportation -when there's enough iron in the liver, it produces hepcidin which binds to ferroportin and blocks further iron absorption by stopping it from transporting iron into duodenum and stopping mobilisation of iron from reticuloendothelial cells

Question 31

What is the transporter proteins called that binds to iron and transport it from GI tract into live stores

Answer 31

Ferroportin