Physiology of red and white blood cells

Abstract

Blood is made up of plasma and formed elements, which are red blood cells, white blood cells and platelets. The red blood cells (erythrocytes) make up the vast majority of the cells present in the blood. Their principal function is the transport of oxygen from the lungs to the tissues and the transport of carbon dioxide from those tissues back to the lungs. This is due to the presence of haemoglobin, a protein that binds easily and reversibly with oxygen. The affinity of haemoglobin for oxygen changes under certain conditions allowing increased off-loading of oxygen at the respiring tissues as required. White blood cells (leucocytes) form the body’s defence against invading pathogens. They can be subdivided into granulocytes and agranulocytes, which have different mechanisms of attack against those pathogens.

Learning objectives

After reading this article, you should be able to:

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describe the structure and function of haemoglobin
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understand the oxygen dissociation curve and the factors affecting it
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describe the different subtypes of leucocyte
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explain the roles of the different leucocytes and how they combat pathogens

Blood is composed of cells and plasma. Red blood cells, white blood cells and platelets form the cellular components. The primary function of blood is to deliver oxygen to the tissues and remove carbon dioxide (CO ₂ ) and waste products. Other important roles include those of immunity and defence, homeostasis and haemostasis. This article concentrates on the physiology of red and white blood cells.

Red blood cells

Structure and function

Red blood cells (erythrocytes) are the most numerous cellular component in blood accounting for approximately 94% of cells. This equates to a cell count of 4.6–6.1 × 10 ¹² /litre in men and 4.2–5.4 × 10 ¹² /litre in women. They are biconcave discs in shape that, by the time they enter the circulation, have no nucleus nor organelles. They are 6.5–8.5 mm in diameter and 1.5–2.5 mm thick. This unique shape gives them a large surface area to facilitate gas exchange and also reversibly deforms to allow passage through the capillary beds. The average life span of the red blood cell in the circulation is 120 days.

The red cell membrane is a lipid bilayer comprised of 50% protein, 40% lipid and 10% carbohydrates. The carbohydrates on the outer surface of the membrane are glycoproteins and glycolipids, which are responsible for the antigenic identity of the cells and have a role in ABO compatibility.

An erythrocyte requires energy to maintain its shape and to maintain the iron contained within it in its reduced (ferrous) state. Adenosine triphosphate (ATP) is produced within the cell via the Embden–Meyerhof pathway and NADPH by the hexose monophosphate shunt (details of which are beyond the scope of this article).

The main functions of erythrocytes are:

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to transport haemoglobin (Hb) which carries oxygen from the lungs to the tissues
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to allow CO ₂to be transported from the tissues to the lungs predominantly in the form of bicarbonate
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to facilitate acid–base balance – Hb is an excellent acid–base buffer.

Life cycle – haematopoiesis and sequestration

All blood cells are produced in red bone marrow. This is active cellular marrow present in all bones in children but that by 20 years of age is predominantly found in flat bones and the proximal portions of the humerus and femur. In the fetus, bloods cells are also produced in the liver and spleen. This can occur in disease states in adults when bone marrow becomes destroyed or fibrosed and is called extramedullary haematopoiesis.

All blood cells are derived from pluripotent uncommitted stem cells that differentiate into one or other type of committed stem cell (progenitor cell). These in turn differentiate into various types of blood cell ( Figure 1 ).

Only 25% of cells in active marrow belong to the erythrocyte- producing series compared with 75% that mature into leucocytes. This is true despite the fact there are 500 times as many erythrocytes in the circulation as leucocytes, as the life span of the leucocyte is short (hours to 21 days) compared to the erythrocyte life span (approximately 120 days).

The development of erythrocytes, termed erythropoiesis, from their dedicated stem cell (pronormoblast) within the bone marrow takes 5–7 days. As differentiation proceeds the cells shrink, Hb is synthesized and in the later stages the nucleus breaks up and disappears. After the final division the cells evolve through the reticulocyte stage, so-called as a reticulum (mesh-like system of ribosomal RNA) can be seen on staining. This then disappears as the cells become mature biconcave discs. Normally, approximately 1–2% of circulating erythrocytes are at the reticulocyte stage. This percentage does increase in certain circumstances such as major blood loss or chronic anaemia when increased erythropoiesis is triggered.

Erythropoiesis is subject to feedback control. It is inhibited by a rise in circulating erythrocytes to a supranormal level and stimulated by anaemia and hypoxia. This feedback control of red cell production is mediated by erythropoietin, a circulating glycoprotein hormone secreted from the juxtaglomerular apparatus of the nephron in response to hypoxia or anaemia.

Over time erythrocytes become damaged or lose shape. These abnormally shaped cells are then sequestered in the spleen and to a lesser extent the liver. At sequestration the haem group is split from Hb and converted to biliverdin and then bilirubin which is excreted in bile while the iron is conserved and recycled via the iron transport protein transferrin or stored in the intracellular protein, ferritin.

Haemoglobin

Hb is a metalloprotein within the erythrocyte responsible for over 99% of oxygen carriage from the lungs to the tissues and accounting for 33% of red cell mass. It comprises of four subunits each containing a polypeptide globin chain and an iron-containing porphyrin called haem. The haem is synthesized from succinic acid and glycine and contains one atom of iron in the reduced, ferrous state (Fe ²⁺ ). One molecule of Hb has four atoms of iron and binds four molecules of oxygen. There are two pairs of polypeptide globin chains in each Hb molecule. Normal adult Hb (HbA) contains two a and two b chains. Another normal variant (HbA ₂ ) accounts for up to 2.5% of Hb and contains two a and two d chains. Fetal Hb (HbF) contains two a and two g chains. The difference in structure of the g chains gives HbF a greater affinity for oxygen thereby allowing the offload of oxygen from the maternal to the fetal circulation.

Oxygen delivery to the tissues and the oxygen dissociation curve

When oxygen (O ₂ ) binds to Hb it forms oxy-haemoglobin. This is a reversible reaction (O ₂ þ Hb 4 HbO ₂ ). The quaternary structure of Hb determines its affinity for oxygen. When HbA takes up O ₂ the two b chains move closer together, when O ₂ is given up they move further apart. Movement of the chains causes a change in the position of the haem groups which assume a relaxed (R) state that favours O ₂ binding or a tense (T) state that reduces O ₂ binding. When Hb binds with oxygen the R state is favoured and additional uptake is facilitated. Combination of the first haem group in the Hb molecule with oxygen increases the affinity of the second haem group for oxygen which consequently increases the affinity of the third haem group for oxygen and so on, meaning that the affinity of the Hb for the fourth oxygen molecule is many times that of the first. This property known as haem–haem interaction results in a sigmoidal curve when saturation is plotted against the partial pressure of oxygen (PO ₂ ) in an oxygen dissociation curve ( Figure 2 ). This high affinity of Hb for oxygen means that total saturation occurs at an alveolar PO ₂ of 13 kPa. This haem–haem interaction also has an advantage at the tissues as the reverse is also true where a smaller fall in PO ₂ is required at the tissues for a given amount of oxygen to be released, thereby encouraging O ₂ offload. In contrast, the dissociation curve for myoglobin is hyperbolic meaning that while myoglobin has a high affinity for oxygen it does not give up oxygen readily. This is an advantage in its role as an oxygen storage protein in muscle ( Figure 2 ).