Haematology Principles

Blood cells are made from heamatopoietic stem cells in bone marrow which differentiate into either:

– Common myeloid progenitors

– Lymphoid progenitors, which give rise to lymphocytes.

One of the most important types of cells is the red blood cell.

– Formed from an erythroid progenitor called reticulocyte.

– Its role is to carry oxygen to tissues around the body

In order to make red blood cells, you have to make the cellular precursors and haemoglobin:

Cellular precursors:

To make reticulocytes, folic acid is needed for thymidine synthesis to make DNA

– This needs Vitamin B12, which acts as a cofactor to transform folic acid to tetrahydrofolate, its active form.

– B12 has a 3-5-year store in the liver, whereas folic acid has a much smaller store in the body, so you need a regular supply.

– Humans acquire all Vitamin B12 from animal sources –> hence vegans take B12 supplements.

– Vitamin B12 is absorbed in the terminal ileum

– This requires intrinsic factor (IF) which is released from the stomach.

– It forms a complex allowing it to bind to the IF receptor in the terminal ileum

– Once in the blood, Vitamin B12 travels bound to the carrier protein transcobalamin 

 

Haemoglobin:

This is the functional molecule of RBCs, which is composed of 4 polypeptide chains – 2 alpha, 2 beta

– Each chain carries a prosthetic haem group which is responsible for binding oxygen

– A haem group consists of an iron (Fe2+) ion (charged atom) held in porphyrin rings, which are bound by their nitrogen atoms to the central Fe2+ ion

– In adults, the most common hemoglobin type is a tetramer (which contains four subunit proteins) called haemoglobin A, consisting of two α and two β subunits non-covalently bound, each made of 141 and 146 amino acid residues respectively

Therefore, in order to make haemoglobin, the body needs to absorb iron from animal and vegetable foods.

– The regulation of iron content in the body is done by controlling its
absorption from the small intestine.

– Fe2+ ions are absorbed on the brush border of the small intestine.

– Iron is transported across to blood using the protein Ferroportin.

– In the blood it is carried bound to protein Transferrin.

– Iron can also be stored in pools within cells as Ferritin.

– This is converted to Hemosiderin if levels are substantially high.

– When iron levels increase in the body, Hepcidin is released by the liver which prevents iron absorption.

– Instead it is converted to ferritin in luminal cells and shed in the faeces.

Plasma Ions

The plasma carries many inorganic ions, which are important for maintaining electrolyte balance.

– Each has a reference range, which can lead to a specific set of symptoms if disturbed.

Ion

[Extracellular] mM

[Intracellular] mM

Na+

145

10

K+

4

140

Ca2+

1

0.0001

Cl-

110

10

Mg2+

2

0.5

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