Synthesis of platelets occurs in the bone marrow by fragmentation of megakaryocytes cytoplasm, derived from the common myeloid progenitor cell. The average time for differentiation of the human stem cell to the production of platelets is about 10 days. The major regulator of platelet formation is thrombopoietin and 95% of this is produced by the liver. Normal platelet count is 150 – 450 x 109/L and the normal lifespan of a platelet is about 10 days. Usually about one-third of the marrow output of platelets may be trapped at any one time in the normal spleen.

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.

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.

It’s crucial that thrombin’s impact is restricted to the injured site. Tissue factor pathway inhibitor (TFPI), which is produced by endothelial cells and found in plasma and platelets, is the first inhibitor to function. It accumulates near the site of harm induced by local platelet activation. Xa and VIIa, as well as tissue factor, are inhibited by TFPI. Other circulating inhibitors, the most potent of which is antithrombin, can also inactivate thrombin and other protease factors directly. Coagulation cofactors V and VIII are inhibited by protein C and protein S. Tissue plasminogen activator (TPA) from endothelial cells facilitates fibrinolysis by promoting the conversion of plasminogen to plasmin.

Passive diffusion is a process that describes the movement down a concentration gradient. This process accounts for movement across small distances like within the cytosol or across membranes. Factors that affect the diffusion of a substance across a membrane are the permeability (p) of the membrane, a difference in concentration across the membrane and the membrane area over which diffusion occurs. The membrane thickness and composition, and the diffusion coefficient of the substance also affects the permeability. Fick’s law describes the rate of diffusion of a substance within a solution, which can be modified to describe the rate of diffusion across a membrane.

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.

An action potential is a self-propagating response, successive depolarisation moving along each segment of an unmyelinated nerve until it reaches the end. It is all-or-nothing and does not decrease in size. Conduction in myelinated fibres is much faster, up to 50 times that of the fastest unmyelinated nerve. Myelinated fibres are insulated except at areas devoid of myelin called nodes of Ranvier. The depolarisation jumps from one node of Ranvier to another by a process called saltatory conduction. Saltatory conduction not only increases the velocity of impulse transmission but also conserves energy for the axon because depolarisation only occurs at the nodes and not along the whole length of the nerve fibre. Larger diameter myelinated nerve fibres conduct nerve impulses faster than small unmyelinated nerve fibres.

Cellular respiration is the process by which cells obtain energy in the form of adenosine triphosphate (ATP). ATP transfers chemical energy from the energy rich substances in the cell to the cell’s energy requiring reactions e.g. active transport, DNA replication and muscle contraction.Cellular respiration is essentially a three step process: 1) Glycolysis, 2)The Krebs cycle, 3)The electron transfer system.The main respiratory substrate used by cells is 6-carbon glucose. Fats and proteins can also be used as respiratory substrates. When fats are being used as the primary energy source, in the absence of glucose, an excess amount of acetyl-CoA is produced, and is converted into acetone and ketone bodies. This can occur in starvation, fasting or in diabetic ketoacidosis. Proteins are used as an energy source only if protein intake is very high, or if glucose and fat sources are depleted.

When the concentration of intracellular Ca2+rises, muscle contraction occurs. The pathway of an action potential is down tube-shaped invaginations of the sarcolemma called T-tubules (transverse tubules). These penetrate throughout the muscle fibre and lie adjacent to the terminal cisternae of the sarcoplasmic reticulum. The voltage changes in the T-tubules result in the opening of sarcoplasmic reticulum Ca2+channels and there is there is release of stored Ca2+into the sarcoplasm. Thus muscle contraction occurs via excitation-contraction coupling (ECC) mechanism.

The resting potential in most neurons has a value of approximately -70 mV.
The threshold potential is generally around -55 mV.
Initial depolarisation when there is Na+influx through ligand-gated Na+channels.
Action potential is an all or nothing response. The size of the action potential is constant and so, the intensity of the stimulus is coded by the frequency of firing of a neuron.
K+efflux is responsible for repolarisation.

Following the action potential, Na+channels remain inactive for a time in a period known as the absolute refractory period where they cannot be opened by any amount of depolarisation. Following this there is a relative refractory period where the temporary hyperpolarisation (due to delayed closure of rectifier K+channels) makes the cell more difficult to depolarise and an action potential can be generated only in response to a larger than normal stimulus. The refractory period limits the frequency at which action potentials can be generated, and ensures that, once initiated, an action potential can travel only in one direction. An action potential is an all or nothing response so the amplitude of the action potential cannot be smaller.

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.

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.

Each motor unit contracts in an all or nothing fashion, i.e. if a motor unit is excited, it will stimulate all of its muscle fibres to contract. The force of contraction of a muscle is controlled by varying the motor unit recruitment (spatial summation), and by varying the firing rate of the motor units (temporal summation). During a gradual increase in contraction of a muscle, the first units start to discharge and increase their firing rate, and, as the force needs to increase, new units are recruited and, in turn, also increase their firing rate. For most motor units, the firing rate for a steady contraction is between 5 and 8 Hz. Because the unitary firing rates for each motor unit are different and not synchronised, the overall effect is a smooth force profile from the muscle. Increasing the firing rate of motor units is temporal summation where the tension developed by the first action potential has not completely decayed when the second action potential and twitch is grafted onto the first and so on. If the muscle fibres are stimulated repeatedly at a faster frequency, a sustained contraction results where it is not possible to detect individual twitches. This is called tetanus.

Protein and phosphate are the primary intracellular anions, while chloride (Cl-) and bicarbonate are the predominant extracellular anions (HCO3-).

At the neuromuscular junction, acetylcholine is released from the prejunctional membrane which acts on cholinergic nicotinic receptors on the postjunctional membrane.

The extrinsic pathway for initiating the formation of prothrombin activator begins with a traumatized vascular wall or traumatized extravascular tissues that come in contact with the blood. Exposed and activated by vascular injury, with plasma factor VII. The extrinsic tenase complex, factor VIIa-tissue factor complex, activates factor X to factor Xa.

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.

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.

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