In order for primary active transport to pump ions against their electrochemical gradient, chemical energy is used in the form of ATP. The Na+/K+-ATPase antiporter pump uses metabolic energy to move 3 Na+ions out of the cell for every 2 K+ions 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.

Total adult haemoglobin comprises about 96 – 98 % of normal adult haemoglobin (HbA). It consists of two alpha (α) and two beta (β) globin chains.

Flow through a tube is dependent upon:
The pressure difference across the ends of the tube (P1– P2)
The resistance to flow provided by the tube (R)
This is Darcy’s law, which is analogous to Ohm’s law in electronics:
Flow = (P1– P2) / R
Resistance in the tube is defined by Poiseuille’s law, which is determined by the diameter of the tube and the viscosity of the fluid. Poiseuille’s law is as follows:
Resistance = (8VL) / (πR4)
Where:
V = The viscosity of the fluid
L = The length of the tube
R = The radius of the tube
Therefore, in simple terms, resistance is directly proportional to the viscosity of the fluid and the length of the tube and inversely proportional to the radius of the tube. Of these three factors, the most important quantitatively and physiologically is vessel radius.
It can be seen that small changes in the radius can have a dramatic effect on the flow of the fluid. For example, the constriction of an artery by 20% will decrease the flow by approximately 60%.
Another important and frequently quoted example of this inverse relationship is that of the radius of an intravenous cannula. Doubling the diameter of a cannula increases the flow rate by 16-fold (r4). This is the reason the diameter of an intravenous cannula in resuscitation scenarios is so important.
*Please note that knowledge of the detail of Poiseuille’s law is not a requirement of the RCEM Basic Sciences Curriculum.

Parasympathetic preganglionic neurones originate in the brainstem from which they run in cranial nerves III, VII, IX and X and also from the second and third sacral segments of the spinal cord. Parasympathetic preganglionic neurones release acetylcholine into the synapse, which acts on cholinergic nicotinic receptors on the postganglionic fibre. Parasympathetic peripheral ganglia are generally found close to or within their target, whereas sympathetic peripheral ganglia are located largely in two sympathetic chains on either side of the vertebral column (paravertebral ganglia), or in diffuse prevertebral ganglia of the visceral plexuses of the abdomen and pelvis. Parasympathetic postganglionic neurones release acetylcholine, which acts on cholinergic muscarinic receptors.

Mitochondria are membrane-bound organelles that are responsible for the production of the cell’s supply of chemical energy. This is achieved by using molecular oxygen to utilise sugar and small fatty acid molecules to generate adenosine triphosphate (ATP). This process is known as oxidative phosphorylation and requires an enzyme called ATP synthase. ATP acts as an energy-carrying molecule and releases the energy in situations when it is required to fuel cellular processes. Mitochondria are also involved in other cellular processes, including Ca2+homeostasis and signalling. Mitochondria contain a small amount of maternal DNA.
Mitochondria have two phospholipid bilayers, an outer membrane and an inner membrane. The inner membrane is intricately folded inwards to form numerous layers called cristae. The cristae contain specialised membrane proteins that enable the mitochondria to synthesise ATP. Between the two membranes lies the intermembrane space, which stores large proteins that are required for cellular respiration. Within the inner membrane is the perimitochondrial space, which contains a jelly-like matrix. This matrix contains a large quantity of ATP synthase.
Mitochondrial disease, or mitochondrial disorder, refers to a group of disorders that affect the mitochondria. When the number or function of mitochondria in the cell are disrupted, less energy is produced and organ dysfunction results.

A membrane potential is a property of all cell membranes, but the ability to generate an action potential is only a property of excitable tissues. The resting membrane is more permeable to K+and Cl-than to other ions (and relatively impermeable to Na+); therefore the resting membrane potential is primarily determined by the K+equilibrium potential. At rest the inside of the cell is negative relative to the outside. In most neurones the resting potential has a value of approximately -70 mV.

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.

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.

An ‘average’ person (70 kg male) contains about 40 litres of water in total, separated into different fluid compartments by biological semipermeable membranes; plasma cell membranes between extracellular and intracellular fluid, and capillary walls between interstitial and intravascular fluid. Around two-thirds of the total fluid (27 L) is intracellular fluid (ICF) and one-third of this (13 L) is extracellular fluid (ECF). The ECF can be further divided into intravascular fluid (3.5 L) and interstitial fluid (9.5 L).
Transcellular fluid refers to any fluid that does not contribute to any of the main compartments but which are derived from them e.g. gastrointestinal secretions and cerebrospinal fluid, and has a collective volume of approximately 2 L.
Osmosis is the passive movement of water across a semipermeable membrane from regions of low solute concentration to those of higher solute concentration.

Diffusion is the passive movement of ions across a cell membrane down their electrochemical or concentration gradient through ion channels. Ion channels can be voltage-gated (regulated according to the potential difference across the cell membrane) or ligand-gated (regulated by the presence of a specific signal molecule). Facilitated diffusion is the process of spontaneous passive transport of molecules or ions down their concentration gradient across a cell membrane via specific transmembrane transporter (carrier) proteins. The energy required for conformational changes in the transporter protein is provided by the concentration gradient rather than by metabolic activity. In secondary active transport there is no direct coupling of ATP but the initial Na+ electrochemical gradient that drives the secondary active transport is set up by a process that requires metabolic energy. Examples include the sodium/calcium exchanger, or the sodium/glucose symporter.