Red Cells 1

Question 1

What are the causes of low Hg levels?

Answer 1

Blood loss
Increased destruction
Lack of/defective production

Question 2

What are the key substances needed for red cell production?

Answer 2

Iron
B12
Folic acid
Erythropoietin

Question 3

Where does red cell breakdown take place?

Answer 3

Reticuloendothelial system
Macrophages in spleen
(also Liver, lymph nodes, lungs)

Question 4

What is the fate of globin in red cell breakdown?

Answer 4

Amino acids reused

Question 5

What is the fate of Haem in red cell breakdown?

Answer 5

Iron - reused

Haem –> Biliverdin –> bilirubin

Question 6

What is the normal life span of a RBC?

Answer 6

120 days

Question 7

How does bilirubin travel in the blood?

Answer 7

Bound (unconjugated) to albumin in plasma

Question 8

What is contained within a RBC?

Answer 8

Membrane
Enzymes
Haemoglobin

Question 9

What are the causes of congenital anaemias?

Answer 9

Genetic defects described in membrane, enzymes or haemoglobin
Reduce red cell survival - (haemolysis)

Question 10

What is the role of skeletal proteins in RBC?

Answer 10

Maintain cell shape and deformability

Question 11

Defects in RBC skeletal proteins can lead to what?

Answer 11

Increased cell destruction

Question 12

What is Hereditary Spherocytosis?

Answer 12

Autosomal dominant
Defect in 5 structural proteins of red cells
Leads to spherical RBC
Removed from circulation in RE system

Question 13

Hereditary Spherocytosis results in defects in which structural proteins?

Answer 13

Ankyrin
Alpha spectrin
Beta spectrin
Band 3
Protein 4.2

Question 14

How does Hereditary Spherocytosis present?

Answer 14

Anaemia
Jaundice
Splenomegaly
Pigment gallstones

Question 15

How is Hereditary Spherocytosis treated?

Answer 15

Folic acid
Transfusion
Splenectomy

Question 16

What are the roles of enzymes in RBC?

Answer 16

Glycolysis (for energy)

Pentose Phosphate shunt (protect from oxidative damage)

Question 17

What enzymes are key in RBC function?

Answer 17

G-6-P dehydrogenase (PP shunt)

Pyruvate kinase

Question 18

What is the role of G-6-P Dehydrogenase?

Answer 18

Produce NADPH

Detoxifies reactive oxygen species

Question 19

G6PD deficiency results in what?

Answer 19

Vulnerable to oxidative damage

Protection against malaria (more common in malarial areas)

Question 20

How is G6PD deficiency transmitted?

Answer 20

X-linked, males more affected

Question 21

How does G6PD deficiency present?

Answer 21

Neonatal jaundice
Drug/infection/broad bean precipitated jaundice and anaemia
Splenomegaly
Pigment gallstones

Question 22

Pyruvate kinase deficiency causes what?

Answer 22

Anaemia
Jaundice
Gallstones
Rigid cells

Question 23

What is the structure of Hemoglobin?

Answer 23

4 Heme (+ 4Fe)
2 a chains
2 b chains

Question 24

Outline Oxygen binding to Haemoglobin?

Answer 24

1st is hard, 2nd 3rd and 4th is ‘easier’

Question 25

What is the role of 2,3 DPG?

Answer 25

Forms tight haemoglobin structure

Question 26

What causes 'right' Bohr shift?

Answer 26

Acidity Increased DPG Increased Temp Increased CO2

Question 27

What causes 'left' Bohr shift?

Answer 27

Alkalinity Decreased DPG Decreased Temp Decreased CO2

Question 28

Outline the inheritance of alpha globin chains?

Answer 28

2 from mother, 2 from father

Question 29

What is the normal adult haemoglobin ratio?

Answer 29

``` Hb A (aaBB) - 97% Hb A2 (aadd) - 2% Hb F (aayy) - 1% ```

Question 30

What are haemoglobinopathies?

Answer 30

Inherited abnormalities in haemoglobin synthesis

Question 31

What is Thalassaemia?

Answer 31

Reduced or absent globin (a or B) chain production | Mutations/deletions

Question 32

What is Sickle cell?

Answer 32

Point mutation leading to structurally abnormal (B) globin chains (Glutamine replaced by Valine in Beta chains)

Question 33

Where is sickle cell endemic?

Answer 33

West/central africa | North india

Question 34

Where is Thalassaemia endemic?

Answer 34

Mediterranean Baltics India Asia/North Oceania

Question 35

What form of inheritance occurs in haemoglobulinaemias?

Answer 35

Autosomal recessive

Question 36

How does 'cell sickling' take place?

Answer 36

Haemoglobin crystallises when deoxygenation and forms a Sickle This process is irreversible when re-oxygenating

Question 37

What are the consequences of HbS polymerisation?

Answer 37

``` Haemolysis Damaged endothelium Pro-inflammatory state Coagulation Vaso-occlusion ```

Question 38

How does Sickle-cell disease present?

Answer 38

``` Painful vaso-occlusive crises in bones Stroke Increased Infection risk Chronic haemolytic anaemia Reduced life expectancy Renal impairment Splenic infarction - hyposplenic ```

Question 39

How is sickle cell pain crisis managed?

Answer 39

Analgesia - opiates Hydration Oxygen ?Antibiotics

Question 40

How is sickle cell disease managed?

Answer 40

``` Prophylaxis (as hyposplenic) Vaccination Penicillin Folic acid) Blood transfusion Hydroxycarbamide Bone marrow transplant ```

Question 41

What is fetal hemoglobin?

Answer 41

alpha alpha gamma gamma

Question 42

Outline 'alpha' thalassaemias

Answer 42

- a/aa | - -/aa (incompatible with life)

Question 43

Outline 'beta' thalassaemias?

Answer 43

Reduced beta chains, more dependence on gamma and delta chains Chronic haemolysis and anaemia

Question 44

What is the spectrum of thalassaemia?

Answer 44

Homozygous alpha zero thalassaemia (no alpha chains, incompatible with life) Beta thalassaemia major (transfusion dependent) Non-transfusion dependent thalassaemia Thalassaemia minor "trait"

Question 45

How does Beta thalassaemia major present?

Answer 45

Severe anaemia from 3-6 months Bone deformities (expansion of bone marrow) Splenomegaly Growth retardation

Question 46

How is Beta thalassaemia major managed?

Answer 46

Chronic transfusion Iron chelation therapy (to manage Iron overload) Bone marrow transplantation

Question 47

Defaults in mitochondrial steps of haem synthesis cause what?

Answer 47

Hereditary sideroblastic anaemia