Anaemia

Question 1

What occurs at the normoblast stage of erythropoeisis?

Answer 1

Haemoglobin accumulation

Question 2

What is a reticulocyte?

Answer 2

Immature erythrocyte
No nucleus
Ribosomal RNA present

Question 3

What does a high reticulocyte count suggest?

Answer 3

Haemorrhage
Splenic sequestration (pooling of blood in enlarged spleen, bone marrow compensates)
Haemolysis

Question 4

How is erythropoeisis stimulated?

Answer 4

Kidney detects hypoxia
Releases erythropoietin
Stimulates haematopoietic stem cells in bone marrow to proliferate and differentiate
Leads to increased production of RBCs

Question 5

What is the life span of an RBC?

Answer 5

120 days

Question 6

How are damaged or Ig coated RBCs removed from the circulation?

Answer 6

Phagocytosed by macrophages in the reticuloendothelial system: spleen, liver, lymph nodes

Question 7

Describe the degradation of haemoglobin and removal of the breakdown products.

Answer 7

Spleen: haem–> biliverdin–> bilirubin (released into blood, binds albumin)
Liver: conjugated bilirubin secreted in bile
Intestines: urobilinogen –> stercobilin –> excreted in faeces
Kidney: urobilinogen excreted in urine

Question 8

Describe the structure of adult haemoglobin.

Answer 8

2 alpha and 2 Beta polypeptide chain

Each chain has an iron containing haem group

Question 9

Describe the binding of oxygen to haemoglobin.

Answer 9

Oxygen binds haem group (4O2 per Hb)
When Hb is in T state it has low binding affinity
R state- high binding affinity
Positive cooperative binding- binding of one oxygen increases affinity
Sigmoid binding curve

Question 10

How is the structure of foetal haemoglobin different to adult?

Answer 10

2alpha and 2 gamma polypeptides

Higher binding affinity for oxygen than maternal Hb to maintain gradient

Question 11

Name two conditions affecting Hb structure.

Answer 11

Thalassaemia- over or under production of specific Hb chains

Sickle Cell disease- DNA base change –> amino acid change –> hydrophobic pockets on Hb

Question 12

Describe the structure of an erythrocyte.

Answer 12

Biconcave disk (diameter 8 microns)
Flexible due to cytoskeleton (must fit through 3.5 micrometer capillaries)

Question 13

What the general signs and symptoms of anaemia?

Answer 13

Shortness of breath
Tired all the time
Reduced exercise tolerance
Headaches
Palpitations
Pallor
Tachycardia

Question 14

In microcytic anaemia, why are RBCs often hypochromic aswell?

Answer 14

Reduced Hb content per cell

Question 15

Give four causes of microcytic anaemia.

Answer 15

Thalassaemia
Anaemia of chronic disease
Iron deficiency
Lead poisoning
Sideroblastic anaemia

Question 16

Give three functions of iron in the body.

Answer 16

Component of haemoglobin and myoglobin
Component of cytochrome enzymes
Enzyme catalyst e.g. collagen synthesis (vit C and Fe2+ for prolyl hydroxylase)

Question 17

How is iron absorbed in the gut?

Answer 17

Gastric acid converts Fe3+ to Fe2+
Fe2+ binds apotransferrin in the duodenum (and jejunum)
Uptake of transferrin via receptor mediated endocytosis (iron released at CURL, receptor and apotransferrin remain bound and recycled to plasma membrane)

Question 18

How is iron stored?

Answer 18

Ferritin

Question 19

What affects iron absorption from the gut?

Answer 19

Reduced: chelating agents e.g. tea, coffee
Reduced acid production e.g. PPIs, H2 antagonists, antacids
Increased: vitamin C (promotes Fe2+ formation)

Question 20

What causes iron deficiency?

Answer 20

Dietary deficiency
Haemorrhage- GI, menorrhagia
Impaired absorption- chelating agents, reduced gastric acid
Pregnancy (increased demands)

Question 21

How do you test for iron deficiency?

Answer 21

Percentage transferrin saturation (best)
Serum Fe2+
Ferritin (not always accurate- acute phase protein so raised in inflammation)

Question 22

How is iron deficiency managed?

Answer 22

Treat cause e.g. Bleeding
Increase dietary intake
Iron supplements- oral, IM
(Transfusion- if severe)

Question 23

What can cause macrocytic anaemia (with hyper segmented neutrophils)?

Answer 23

B12 or folate deficiency

Myelodysplasia

Question 24

What can cause B12 deficiency?

Answer 24

Dietary deficiency
Impaired absorption e.g. IBD
Pernicious anaemia- autoimmune attack of parietal cells, loss of intrinsic factor
(Takes years to produce anaemia)

Question 25

What causes folate deficiency?

Answer 25

Diet deficiency
Malabsorption
Increased demand e.g. Pregnancy, sickle cell disease
Drugs e.g. AEDs,co trimoxazole

Question 26

What can cause normocytic anaemia?

Answer 26

Anaemia of chronic disease
Mixed deficiency of Fe and B12/folate
Bone marrow failure

Question 27

What causes anaemia of chronic disease?

Answer 27

Chronic inflammation and cytokines
Reduce EPO production
Reduced erythrocyte survival

Question 28

Give three causes of haemolytic anaemia.

Answer 28

Sickle cell disease
G6PDH deficiency
Hereditary spherocytosis
Autoimmune haemolytic anaemia
Mechanical e.g. Prosthetic heart valves
Sepsis

Question 29

Describe the presentation of haemolytic anaemia.

Answer 29

General anaemia symptoms.
Splenomegaly
Jaundice (pre hepatic)
Pain (crisis–> ischaemia)

Question 30

What investigations would you do in the case of haemolytic anaemia?

Answer 30

Blood films- reticulocytosis, +/- spherocytes, rbc fragments
Direct Coombs test
Bilirubin in blood
LDH (raised)
Haptoglobin (reduced- mops up Hb)

Question 31

What is the Embden Meyerhof Pathway in RBCs?

Answer 31

Glucose–> lactate

Produces ATP

Question 32

What is the role of the pentode phosphate pathway in RBCs?

Answer 32

Metabolise glucose 6 phosphate

Generates NADPH - antioxidant, mops up ROS, maintains -SH groups

Question 33

From which common progenitor cell (derived from multipotent haematopoietic stem cell) do erythrocytes originate?

Answer 33

Common myeloid progenitor