Red Cells 1

Question 1

What is the mnemonic for remembering the causes of microcytic anaemia?

Answer 1

TAILS:
- Thalassaemia
- Anaemia of chronic disease
- Iron deficiency anaemia
- Lead poisoning
- Sideroblastic anaemia

Question 2

Anaemia of chronic disease often occurs with…

Answer 2

chronic kidney disease due to reduced production of erythropoietin by the kidneys, the hormone responsible for stimylating red blood cell production.
Treatment is with Erythropoietin.

Question 3

There are 3 As and 2 Hs for normocytic anaemia:

Answer 3

• Acute blood loss
• Anaemia of chronic disease
• Aplastic anaemia
• Haemolytic anaemia
• Hypothyroidism

Question 4

What are the two types of macrocytic anaemia?

Answer 4

• megaloblastic: results from impaired DNA synthesis, preventing cells from dividing normally. Rather than dividing, they grow into large, abnormal cells.
• normoblastic.

Question 5

megaloblastic macrocytic anaemia is caused by:

Answer 5

B12 deficiency
Folate deficiency

Question 6

normoblastic macrocytic anaemia is caused by:

Answer 6

• alcohol
• reticulocytosis (usually from haemolytic anaemia or blood loss), refers to an increased concentration of immature blood cells (reticulocytes).
• hypothyroidism
• liver disease
• drugs, such as azathioprine, methotrexate

Question 7

what are some symptoms and signs specific to iron deficiency anaemia?

Answer 7

Symptoms:
- Pica (dietary cravings for abnormal things, such as dirt or soil)
- Hair loss

Signs:
- koilonychia (spoon-shaped nails)
- angular cheilitis
- atrophic glossitis (smooth tongue)
- brittle hair and nails

Question 8

jaundice could indicate which type of anaemia?

Answer 8

haemolytic

Question 9

bone deformities can indicate which type of anaemia?

Answer 9

thalassaemia

Question 10

which substances are required for red cell production?

Answer 10

• Metals: iron, copper, cobalt, manganese
• Vitamins: B12, folic acid, thiamine, Vit B6, C, E
• Amino acids
• Hormones: erythropoietin, GM-CSF, - androgens, thyroxine

Question 11

what is the normal life span of red blood cells?

Answer 11

120 days

Question 12

Why could jaundice indicate haemolytic anaemia? Talk about breakdown

Answer 12

Hemolysis: When red blood cells break down, it’s called hemolysis.
Bilirubin release: When red blood cells break down, they release hemoglobin, which is then converted into bilirubin.
Liver function: The liver normally processes and removes bilirubin from the blood.
Jaundice presentation: If the rate of red blood cell destruction is too high for the liver to handle, bilirubin levels rise in the blood, causing jaundice.

Question 13

Describe hereditary spherocytosis and its presentation

Answer 13

• most commonly autosomal dominant
• defects in 5 different structural proteins of red blood cell: ankyrin, alpha spectrin, beta spectrin, band 3, protein 4.2.
• red cells are spherical
• removed from circulation by the RE system (extravascular)

Clinical presentation:
- anaemia
- jaundice (neonatal)
- splenomegaly
- pigment gallstones

Question 14

Hereditary spherocytosis treatment

Answer 14

• folic acid (increased requirements)
• transfusion
• splenectomy if anaemia very severe

Question 15

what is the role of Glucose 6 Phosphate Dehydrogenase (G6DP) in red cell glucose metabolism?

Answer 15

Protects red cell proteins (haemoglobin) from oxidative damage:
- produces NADPH - vital for reduction of glutathione
- reduced glutathione scavenges and detoxifies reactive oxygen species

Question 16

Describe G6PD deficiency and its clinical presentation

Answer 16

• commonest disease causing enzymopathy in the world, many genetic variants
• cells vulnerable to oxidative damage, however confer protection against malaria
• X-linked > affects males, female carries

Clinical presentation, variable:
- variable degrees of anaemia from mild to severe
- neonatal jaundice
- splenomegaly
- pigment gallstones

Haemolysis is triggered by oxidative stress.

Question 17

What are some triggers to haemolysis in G6PD deficiency?

Answer 17

Caused by oxidative stress
- infection: acute illness e.g. DKA, broad (Fava) beans
- Drugs: antimalarials, sulphonamides and sulphones, antibacterials: nitrofurantoin, analgesics: aspirin, antihelminthics, vitamin K analogues.

Question 18

normal adult haemoglobin structure

Answer 18

Composed of haem molecule and:
- 2 alpha chains
- 4 alpha genes (Chr16)
- 2 beta chains
- 2 beta genes (Chr11)

Question 19

What are some inherited abnormalities of haemoglobin synthesis?

Answer 19

Reduced or absent globin chain production:
- Thalassaemia (alpha, beta, delta, gamma)

Mutations leading to structurally abnormal globin chain:
- HbS (sickle cell), HbC, HbD, HbE, HbO Arab…

Question 20

describe the structure of sickle cell haemoglobin (HbS)

Answer 20

Composed of haem molecule and:
- 2 alpha chains
- 2 beta (sickle) chains, caused by point mutation

Question 21

how is sickle cell inherited?

Answer 21

Sickle cell anaemia is an autosomal recessive condition affecting the gene for beta-globin on chromosome 11. One abnormal copy of the gene results in sickle-cell trait. Patients with sickle-cell trait are usually asymptomatic. They are carriers of the condition. Two abnormal copies result in sickle-cell disease.

Question 22

What are the steps in the pathophysiology of sickle cell disease?

Answer 22

1. Haemoglobin S polymerisation
2. vaso-occlusion
3. endothelial dysfunction
4. sterile inflammation

Question 23

what are some triggers for a sickle cell crisis?

Answer 23

• infection
• hypoxia
• dehydration
• cold
• stress

Question 24

What does sickle cell crisis refer to?

Answer 24

A spectrum of acute exacerbations caused by sickle cell disease. These range from mild to lige-threatening:
- vaso-occlusive crisis
- splenic sequestration crisis
- aplastic crisis
- acute chest syndrome

Question 25

sickle cell disease clinical presentations

Answer 25

- painful vaso-occlusive crises: bone - chest crisis - stroke - increased infection risk > hyposplenism - chronic haemolytic anaemia: gallstones, aplastic crisis - sequestration crises: spleen and liver

Question 26

what is the management for a painful sickle cell crisis?

Answer 26

- often requires opiates - hydration - oxygen - consider antibiotics

Question 27

general management of sickle cells disease

Answer 27

- Avoid triggers for crises, such as dehydration - Up-to-date vaccinations - Antibiotic prophylaxis to protect against infection, typically with penicillin V (phenoxymethylpenicillin) - Hydroxycarbamide (stimulates HbF) - Crizanlizumab - Blood transfusions for severe anaemia - Bone marrow transplant can be curative

Question 28

what causes thalassaemia?

Answer 28

A genetic defect in the protein chains that make up haemoglobin. - defects in alpha-globin chains lead to alpha thalassaemia - defects in beta-globin chains lead to beta thalassaemia - both conditions are autosomal recessive

Question 29

Describe beta-thalassaemia major.

Answer 29

Patients with beta thalassaemia major are homozygous for the deletion genes. They have no functioning beta-globin genes. This is the most severe form and usually presents with severe anaemia and failure to thrive in early childhood.

Question 30

Beta-thalassaemia major clinical features

Answer 30

- severe anaemia - present at 3-6 months of age - expansion of ineffective bone marrow - bony deformities - splenomegaly - growth retardation - life expectancy untreated or with irregular transfusions < 10 years.

Question 31

Beta-thalassaemia major treatment

Answer 31

- chronic transfusion support 4-6 weekly, but can cause iron overloading - iron chelation therapy - good adherence to chelation > life expectancy near normal, requires regular monitoring, ferritin and MRI scans - bone marrow transplantation can be curative - gene therapy

Question 32

defects in the mitochondrial steps of haem synthesis result in?

Answer 32

sideroblastic anaemia

Question 33

defects in cytoplasmic steps result in?

Answer 33

porphyrias