Exercise Physiology and Pharmacology

5 litres of arterial blood contains 1L oxygen. 15ml is physically dissolved and the remainder is bound to haemoglobin.

Regular breathing involves the diaphragm and external intercostal muscles. Abdominal muscles press upwards when breathing out and lung elasticity recoil occurs.

When forcefully breathing, the sternum, internal intercostal muscles and abdominal muscles are also involved, and the diaphragm contracts more.

Carotid chemoreceptors release an excitatory input to inspiratory neurons of the medulla oblongata when arterial PO2 decreases, more non-CO2 acids are produced and arterial PCO2 decreases.

Opioid abuse leads to death typically as these drugs decrease the activity of pacemaker neurones in the medulla which drive breathing.

Carbon monoxide poisoning occurs as haemoglobin binds CO more readily than O2 and also loses co-operativity when this occurs.

Skeletal muscle is controlled by somatic motor nerves leading to muscle action potential, causing calcium to rise and contraction to occur.

Skeletal muscle cells are multinucleate and made up of hundreds of contractile myofibrils including thick myosin fibres and thin actin and troponin fibres.

Transverse tubules extend the plasmalemma deep into the cell and the sarcoplasmic reticulum stores calcium ions.

Action potential is propagated into the T tubules, activating calcium ion release from the sarcoplasmic reticulum. The calcium ions bind troponin causing tropomyosin to move so that myosin can bind troponin. ATP hydrolysis provides the energy for this process to occur and a cycle of ATP binding, hydrolysis and ADP/Pi release drives myosin.

ATP hydrolysis in skeletal muscle contraction drives cross-bridge cycling (myosin ATPase), restoration of plasma membrane ion gradients (Na+/K+ pump) and return of calcium from cytosol to sarcoplasmic reticulum.

Skeletal muscle supplies of ATP are therefore used up very quickly and restored using phosphocreatine, mitochondrial oxidative phosphorylation and glycolysis.

slow-twitch fibres contain lots of mitochondria, myoglobin and small blood vessels. Fast-twitch fibres contain few mitochondria but lots of glycolytic enzymes and large glycogen stores.

Type I slow oxidative fibres are slow to tire, have a good blood supply and contract slowly, type IIa fast-oxidative glycolytic fibres are intermediate in terms of rate of fatigue and contraction speed, and type IIb/x fast-glycolytic fibres are fast to tire, contract quickly and have a poorer blood supply.

Multiple muscle fibres of same type are innervated by 1 motor neurone but whole skeletal muscles are made up of many motor units of different types.

NMJ blockers cause paralysis and some are used alongside anaesthetics. Depolarising NMJ blockers mimic ACh but are much slower to hydrolyse, causing sustained contraction. Non-depolarising NMJ blockers inhibit nAChR, preventing ACh binding and EPP formation eg tubocurarine.

Botulinum toxin A inhibits ACh release → flaccid paralysis. Can be used for local muscle paralysis to treat excessive sweating/facial wrinkles.

Dantrolene inhibits release of calcium ions from sarcoplasmic reticulum. Can be used to treat muscle spasticity or malignant hyperthermia.

Malignant hyperthermia occurs due to a genetic mutation which can cause calcium ions to be released from the sarcoplasmic reticulum when exposed to certain anaesthetics/suxamethonium.

Low intensity aerobic exercise increases number of mitochondria and capillaries in skeletal muscle. Endurance training causes fast-glycolytic fibres to become fast-oxidative-glycolytic fibres. High intensity strength training increases diameter of fast-twitch fibres (hypertrophy), increases expression of glycolytic enzymes and causes greater synchronisation of motor unit recruitment.

When exercising, the brain ‘exercise centres’ reduce parasympathetic output to heart and increase sympathetic output to heart, veins, abdominal arterioles and kidneys. This causes increased cardiac output and increased vasoconstriction in abdominal organs and kidneys.

The contraction of skeletal muscle causes local chemical changes which leads to dilation of muscle arterioles and increased local blood flow in muscle. The local chemical changes also stimulate muscle chemoreceptors which send signals to the medullary cardiovascular centre.

Ventricular filling time decreases in response to exercise so venous return must increase: increased skeletal muscle pump, increased respiratory pump, increased venous tone and increased blood flow into veins.

Oxygen consumption increases in proportion to exercise intensity up to a point (VO2 max). The limiting factor is usually cardiac output.

Increased heart stroke volume is as a result of heart remodelling, more skeletal muscle blood vessels and increased blood volume.