MEH - Haemopoiesis

Question 1

Where are most red blood cells, platelets and white blood cells produced?

Answer 1

Bone marrow

Question 2

Where is bone marrow mainly distributed in adulthood?

Answer 2

Pelvis, sternum, skull, ribs, vertebrae

Question 3

How are blood cells produced?

Answer 3

A multipotential haematopoietic stem cell becomes either a common myeloid progenitor or a common lymphoid progenitor.

The lymphoid progenitors form B and T lymphocytes, and the myeloid progenitors form thrombocytes, monocytes, basophils, neutrophils and eosinophils

Question 4

What cells are included in the reticuloendothelial system (RES)?

Answer 4

Monocytes, macrophages, kupffer cells, tissue histiocytes, microglial cells in CNS

Question 5

What do RES cells in the spleen dispose of?

Answer 5

Damaged or old red blood cells

Question 6

What are the functions of red blood cells?

Answer 6

Primary - to deliver oxygen to the tissues

• carry haemoglobin
• maintain haemoglobin in its reduced (ferrous) state
• generate energy (ATP)
• maintain osmotic equilibrium

Question 7

Do red blood cells have a cell membrane?

Answer 7

Yes, a lipid bilayer. They also have membrane proteins inserted into it

Question 8

At what age does the switch from foetal to adult haemoglobin occur?

Answer 8

Around 3-6 months of age

Question 9

What is the function of the globin chains?

Answer 9

• protect haem molecule from oxidation
• confer solubility
• permits variation in oxygen affinity

Question 10

What shape is an oxygen dissociation curve?

Answer 10

Sigmoidal

Question 11

Why do people with too many red blood cells get jaundiced?

Answer 11

Excess of red blood cell destruction causes an excess of bilirubin formation which leads to jaundice

Question 12

What is the function of the RES?

Answer 12

Cells identify and mount an appropriate immune response to foreign antigens

Question 13

What are the main organs of the RES?

Answer 13

Spleen and liver

Question 14

What is a peripheral blood count of haemoglobin used to measure with regards to red blood cells?

Answer 14

Their effectiveness. Normal range is 130-180 g/L (or 115-165 g/L for females)

Question 15

What is a red blood count used to measure with regards to red blood cells?

Answer 15

How many red blood cells are present. Normal range is 4.5-6.5 x 10^12/L (3.9-5.6 in women)

Question 16

What is a peripheral blood count of mean cell volume used to measure with regards to red blood cells?

Answer 16

How large the cells are. Normal range is 80-100 fL

Question 17

How large are red blood cells?

Answer 17

8 micrometres diameter, and they can fit through the capillaries with a diameter of 3.5 micrometres

Question 18

True or false - haemoglobin exists in three configurations?

Answer 18

False - it exists in two (oxyhaemoglobin/relaxed, and deoxyhaemoglobin/tight)

Question 19

Which chromosome is the gene for the globin chain formation found on?

Answer 19

The globin gene clusters on chromosome 11 and 16.

Question 20

How is erythropoiesis controlled by oxygen levels in the body?

Answer 20

• reduced pO2 detected in interstitial peritubular cells in kidney
• increased production of erythropoietin (hormone)
• this stimulates maturation and release of red cells from bone marrow
• haemoglobin rises
• pO2 rises
• erythropoietin production falls

Question 21

What are the two main metabolic pathways in red cells?

Answer 21

1) glycolysis - generates ATP

2) pentose phosphate - generates NADPH

Question 22

True or false - there is no mechanism of excreting iron?

Answer 22

True

Question 23

Give some examples of ‘available’ iron

Answer 23

• haemoglobin
• myoglobin
• tissue iron (enzyme systems)
• transported iron (‘serum iron’)

Question 24

Give some examples of ‘stored’ iron

Answer 24

• ferritin

- haemosiderin (macrophage iron)

Question 25

How do macrophages obtain iron?

Answer 25

They 'eat' old senescent red blood cells. Mainly occurs in splenic macrophages and Kupffer cells of the liver

Question 26

Roughly how much iron enters and leaves the body each day?

Answer 26

1-2 mg

Question 27

Roughly how much iron is required each day in the diet?

Answer 27

10-15 mg

Question 28

What is the diffference between haem and non-haem iron?

Answer 28

Haem iron is from meat sources, while non-haem is from beans, cereals etc

Question 29

What form is haem iron in?

Answer 29

Enters enterocyte and released as Fe2+, so it is FERROUS

Question 30

What form is non-haem iron in?

Answer 30

Mainly Fe3+ (FERRIC) - reduced to ferrous iron before being transported across the intestinal epithelium

Question 31

How does iron enter the bloodstream from the stomach acid?

Answer 31

- found in Fe3+ form in stomach acid - binds to transferrin and enters cells through apical surface of the duodenum and upper jejunum - becomes Fe3+ again in cell - reduced to Fe2+ then moves through cell membrane into blood via ferroportin

Question 32

How is iron taken into cells (eg RBCs)?

Answer 32

Iron-transferrin complex binds to transferrin receptor (TfR). Erythroid cells contain the highest number of these receptors.

Question 33

Which vitamin enhances absorption of iron?

Answer 33

Vitamin C

Question 34

Give some examples of regulators of iron absorption

Answer 34

- regulation of transporters - expression of receptors - hepcidin and cytokines - crosstalk between the epithelial cells and other cells eg macrophages

Question 35

How does hepcidin control iron uptake?

Answer 35

- high levels of iron are detected causing the liver to secrete hepcidin - hepcidin degrades ferroportin, a protein involved in moving iron out of cells - this prevents iron release from macrophages and iron absorption from the gut

Question 36

What are the symptoms of anaemia?

Answer 36

- tiredness - reduced O2 carrying capacity leading to pallor, reduced exercise tolerance - angina, palpitations, heart failure - epithelial changes

Question 37

What would a test showing a lowered ferritin level show about an individual?

Answer 37

They are likely to be iron deficient

Question 38

Give some features likely to be observed in a blood film of an anaemic patient

Answer 38

- hypochromic (low Hb content) - microcytic (low mean cell volume) - anisopoikilocytosis (change in size and shape of RBCs) - low reticulocyte haemoglobin content

Question 39

How is iron deficiency treated?

Answer 39

- dietary advice - oral iron supplements - intramuscular iron injections - intravenous iron - transfusion (only in severe cases)

Question 40

Why is free iron considered dangerous?

Answer 40

When binding capacity of transferrin is exceeded, Fe2+ can produce highly reactive hydroxyl and lipid radicals, which damage the lipid membrane nucleic acids and proteins. Excess iron is deposited in tissues

Question 41

What is haemochromatosis?

Answer 41

A disorder of iron excess resulting in end organ damage due to iron deposition

Question 42

What does haemochromatosis cause?

Answer 42

Liver cirrhosis, diabetes mellitus, hypergonadism, cardiomyopathy, arthropathy and skin pigmentation

Question 43

How is hereditary haemochromatosis inherited?

Answer 43

Autosomal recessive mutation in a gene designated HFE on the chromosomes

Question 44

How does a gene mutation cause haemochromatosis?

Answer 44

- Normally, HFE protein competes with transferrin for binding to the transferrin receptor - mutated HFE can't bind, so transferrin has no competition - too much iron enters cells

Question 45

What is transfusion associated haemosiderosis?

Answer 45

Accumulation of iron in the bodies of patients who have received frequent blood transfusions, eg patients with thalassaemia