The electron transfer system is responsible for most of the energy produced during respiration. The is a system of hydrogen carriers located in the inner mitochondrial membrane. Hydrogen is transferred to the electron transfer system via the NADH2molecules produced during glycolysis and the Krebs cycle. As a result, a H+ion gradient is generated across the inner membrane which drives ATP synthase. The final hydrogen acceptor is oxygen and the H+ions and O2 combine to form water.

For an action potential to occur, the membrane must become more permeable to Na+and the Na+influx must be greater than the K+efflux. An action potential occurs when depolarisation of the membrane reaches threshold potential. The membrane must be out of the absolute refractory period, however an action potential can still occur in a relative refractory period but only in response to a larger than normal stimulus.

Darcy’s law states that flow through a tube is dependent on the pressure differences across the ends of the tube (P1 – P2) and the resistance to flow provided by the tube (R). Resistance is due to frictional forces and is determined by the length of the tube (L), the radius of the tube (r) and the viscosity of the fluid flowing down that tube (V). The radius of the tube has the largest effect on resistance and therefore flow – this explains why smaller gauge cannulas with larger diameters have a faster rate of flow. Increased viscosity, as seen in polycythemia, will slow the rate of blood flow through a vessel.

In order for primary active transport to pump ions against their electrochemical gradient, chemical energy is used in the form of ATP. This is facilitated by the Na+/K+-ATPase antiporter pump, which uses metabolic energy to move 3 Na+ions out of the cell for every 2 K+ions that come in, against their respective electrochemical gradients. As a result, the cell the maintains a high intracellular concentration of K+ions and a low concentration of Na+ions.

The vast majority of systems within the body work by negative feedback mechanisms. This negative feedback refers to the way that effectors act to move the variable in the opposite direction to the change that was originally detected. Because there is an inherent time delay between detecting a change in a variable and effecting a response, the negative feedback mechanisms cause oscillations in the variable they control. There is a narrow range of values within which a normal physiological function occurs and this is called the ‘set point’. The release of oxytocin in childbirth is an example of positive feedback.

The first place that haematopoiesis occurs in the foetus is in the yolk sac. Later on, it occurs in the liver and spleen, which are the major hematopoietic organs from about 6 weeks until 6 – 7 months gestation. At this point, the bone marrow becomes the most important site. Haemopoiesis is restricted to the bone marrow in normal childhood and adult life.

Haemoglobin is composed of four polypeptide globin chains each with its own iron containing haem molecule. Haem synthesis occurs largely in the mitochondria by a series of biochemical reactions commencing with the condensation of glycine and succinyl coenzyme A under the action of the key rate-limiting enzyme delta-aminolevulinic acid (ALA) synthase. The globin chains are synthesised by ribosomes in the cytosol. Haemoglobin synthesis only occurs in immature red blood cells.
There are three types of haemoglobin in normal adult blood: haemoglobin A, A2 and F:
– Normal adult haemoglobin (HbA) makes up about 96 – 98 % of total adult haemoglobin, and consists of two alpha (α) and two beta (β) globin chains. 
– Haemoglobin A2 (HbA2), a normal variant of adult haemoglobin, makes up about 1.5 – 3.5 % of total adult haemoglobin and consists of two α and two delta (δ) globin chains.
– Foetal haemoglobin is the main Hb in the later two-thirds of foetal life and in the newborn until approximately 12 weeks of age. Foetal haemoglobin has a higher affinity for oxygen than adult haemoglobin. 
Red cells are destroyed by macrophages in the liver and spleen after , 120 days. The haem group is split from the haemoglobin and converted to biliverdin and then bilirubin. The iron is conserved and recycled to plasma via transferrin or stored in macrophages as ferritin and haemosiderin. An increased rate of haemoglobin breakdown results in excess bilirubin and jaundice.

Haemoglobin is a 64.4 kd tetramer consisting of two pairs of globin polypeptide chains: one pair of alpha-like chains, and one pair of non-alpha chains. The chains are designated by Greek letters, which are used to describe the particular haemoglobin (e.g., Hb A is alpha2/beta2).

Two copies of the alpha-globin gene (HBA2, HBA1) are located on chromosome 16 along with the embryonic zeta genes (HBZ). There is no substitute for alpha globin in the formation of any of the normal haemoglobins (Hb) following birth (e.g., Hb A, Hb A2, and Hb F). Thus, absence any alpha globin, as seen when all 4 alpha-globin genes are inactive or deleted is incompatible with extrauterine life, except when extraordinary measures are taken.

A homotetramer of only alpha-globin chains is not thought to occur, but in the absence of alpha chains, beta and gamma homotetramers (HbH and Bart’s haemoglobin, respectively) can be found, although they lack cooperativity and function poorly in oxygen transport. The single beta-globin gene (HBB) resides on chromosome 11, within a gene cluster consisting of an embryonic beta-like gene, the epsilon gene (HBE1), the duplicated and nearly identical fetal, or gamma globin genes (HBG2, HBG1), and the poorly expressed delta-globin gene (HBD). A heme group, consisting of a single molecule of protoporphyrin IX co-ordinately bound to a single ferrous (Fe2+) ion, is linked covalently at a specific site to each globin chain. If the iron is oxidized to the ferric state (Fe3+), the protein is called methaemoglobin.

Alpha globin chains contain 141 amino acids (residues) while the beta-like chains contain 146 amino acids. Approximately 75 percent of haemoglobin is in the form of an alpha helix. The non helical stretches permit folding of the polypeptide upon itself. Individual residues can be assigned to one of eight helices (A-H) or to adjacent non helical stretches.

Heme iron is linked covalently to a histidine at the eighth residue of the F helix (His F8), at residue 87 of the alpha chain and residue 92 of the beta chain. Residues that have charged side groups, such as lysine, arginine, and glutamic acid, lie on the surface of the molecule in contact with the surrounding water solvent. Exposure of the hydrophilic (charged) amino acids to the aqueous milieu is an important determinant of the solubility of haemoglobin within the red blood cell and of the prevention of precipitation.

The haemoglobin tetramer is a globular molecule (5.0 x 5.4 x 6.4 nm) with a single axis of symmetry. The polypeptide chains are folded such that the four heme groups lie in clefts on the surface of the molecule equidistant from one another.

Erythrocytes have a normal lifespan of about 120 days. Mature erythrocytes are biconcave discs with no nucleus, ribosomes or mitochondria but with the ability to generate energy as ATP by the anaerobic glycolytic pathway. The red cell membrane consists of a bipolar lipid layer with a membrane skeleton of penetrating and integral proteins anchoring carbohydrate surface antigens. The shape and flexibility of red cells allows them to deform easily and pass through capillaries.

Potassium (K+) is the principal intracellular ion; approximately 4 mmol/L is extracellular (3%) and 140 mmol/L intracellular (97%).