The Nernst equation is used to calculate the membrane potential at which the ions are in equilibrium across the cell membrane.

The normal resting membrane potential is -70 mV (not + 70 mV).

The equation is:
E = RT/FZ ln {[X]o
/[X]i}

Where:
E is the equilibrium potential
R is the universal gas constant
T is the absolute temperature
F is the Faraday constant
Z is the valency of the ion
[X]o is the extracellular concentration of ion X
[X]i is the intracellular concentration of ion X.

A major source of caloric expenditure and oxygen consumption in the body is work of breathing (WOB) and 70% of this is to overcome elastic forces. The remaining 30% is for flow-resistive work

In a normal patient breathing normally, the total area of hysteresis pressure volume curve represents the flow-resistive WOB.

The area of the expiratory resistive work increases during an asthma attack making the compliance curve larger in area. The larger the area the greater the work required to breathe.

In situations of poisoning or drug overdose with acid dugs like salicylates and barbiturates, forced alkaline diuresis may be used.

With regards to overdose with alkaline drugs, forced acid diuresis is used.

By changing the pH of the urine, the ionised portion of the drug stays in the urine, and this prevents its diffusion back into the blood. Charged molecules do not readily cross biological membranes.

The process involves the infusion of specific fluids at a rate of about 500ml per hour. This requires monitoring of the central venous pressure, urine output, plasma electrolytes, especially potassium, and blood gas analysis.

The fluid regimen recommended is:
500ml of 1.26% sodium bicarbonate (not 200ml of 8.4%)
500ml of 5% dextrose and
500ml of 0.9% sodium chloride.

Hypoxic Pulmonary vasoconstriction (HPV) reflects the constriction of small pulmonary arteries in response to hypoxic alveoli (.i.e.; PO2 below 80-100mmHg or 11-13kPa).

These blood vessels become independent of the nerve stimulus, when blood with a high PO2 flows through the lung which contains a low alveolar PO2.

Thus a low PO2 within the alveoli has been shown to impact on hypoxic pulmonary vasoconstriction (HPV) more than a low PO2 within the blood.

HPV results in the blood flow being directed away from poorly ventilated areas of the lung and helps to reduce the ventilation/perfusion mismatch (not increase).

In animals, volatile anaesthetic agents can diminish HPV, while in adults, the evidence proves less persuading, in spite of the fact that it certainly doesn’t strengthen the effects.

HPV response will be suppressed by 20 parts per million (ppm) of nitric oxide.

Osmolarity refers to the osmotic pressure generated by the dissolved solute molecules in 1 L of solvent. Measurements of osmolarity are temperature dependent because the volume of the solvent varies with temperature. The higher the osmolarity of a solution, the more it attracts water from an opposite compartment.

Osmolarity can be computed using the following formulas:

Osmolarity = Concentration x number of dissociable particles; OR
Plasma osmolarity (Posm) = 2([Na+]) + (glucose in mmol/L) + (BUN in mmol/L)

Posm = 2 (144) + 3.5 + 9.5 = 301 mOsm/L

Suppose there is electrical neutrality, the formula will double the cation activity to account for the anions.

Plasma osmolarity (Posm) = 2([Na+] + [K+]) + (glucose in mmol/L) + (BUN in mmol/L)

Posm = 2 (144 + 6) + 3.5 + 9.5 = 313 mOsm/L

The blood brain barrier (BBB) consists of the ultrafiltration barrier in the choroid plexus and the barrier around cerebral capillaries. The barrier is made by endothelial cells which line the interior of all blood vessels. In the capillaries that form the blood–brain barrier, endothelial cells are wedged extremely close to each other, forming so-called tight junctions.

Outside of the BBB lies the hypothalamus, third and fourth ventricles and the chemoreceptor trigger zone (CTZ).

Water, oxygen and carbon dioxide cross the BBB freely but glucose is controlled. The ability of chemicals to cross the barrier is proportional to their lipid solubility, not their water solubility. It’s ability to cross is inversely proportional to their molecular size and charge.

In neonates, the BBB is less effective than in adults. This is why there is increased passage of opioids and bile salts (kernicterus) into the neonatal brain.

In meningitis, the effectiveness and permeability of the BBB is affected, and as a result, this effect helps the passage of antibiotics which would otherwise not normally be able to cross.

Skeletal muscle blood flow is in the range of 1-4 ml/min per 100 g when at rest. Blood flow can reach 50-100 ml/min per 100 g during exercise. With maximal vasodilation, blood flow can increase 20 to 50 times.

The adrenal medulla releases catecholamines and increases neural sympathetic activity during exercise. Normally, alpha-1 and alpha-2 would cause vasoconstriction in the muscle groups being used, but vasodilatory metabolites override these effects, resulting in a so-called functional sympathectomy. Local hypoxia and hypercarbia, nitric oxide, K+ ions, adenosine, and lactate are some of the stimuli that cause vasodilation.

However, the splanchnic and cutaneous circulations, which supply inactive muscles, vasoconstrict.

Sympathetic cholinergic innervation of skeletal muscle arteries is found in some species (such as cats and dogs, but not humans). Vasodilation is induced by stimulating smooth muscle beta-2 adrenoreceptors, but at rest, the alpha-adrenoreceptor effects of adrenaline and noradrenaline predominate. During exercise, the skeletal muscle pump promotes venous emptying, but it does not necessarily increase blood flow.

The bispectral index (BIS) is one of several systems used in anaesthesiology as of 2003 to measure the effects of specific anaesthetic drugs on the brain and to track changes in the patient’s level of sedation or hypnosis. It is a complex mathematical algorithm that allows a computer inside an anaesthesia monitor to analyse data from a patient’s electroencephalogram (EEG) during surgery. It is a dimensionless number (0-100) that is a summative measurement of time domain, frequency domain and high order spectral parameters derived from electroencephalogram (EEG) signals.

Sleep and anaesthesia have similar behavioural characteristics but are physiologically different but BIS monitors can be used to measure sleep depth. With increasing sleep depth during slow-wave sleep, BIS levels decrease. This correlates with changes in regional cerebral blood flow when measured using positron emission tomography (PET).

BIS shows a dose-response relationship with the intravenous and volatile anaesthetic agents. Opioids produce a clinical change in the depth of sedation or analgesia but fail to produce significant changes in the BIS. Ketamine increases CMRO2 and EEG activity.

BIS is unable to predict movement in response to a surgical stimulus. Some of these are spinal reflexes and not perceived by the cerebral cortex.

BIS is used during cardiopulmonary bypass to measure depth of anaesthesia and an index of cerebral perfusion. However, it cannot predict subtle or significant cerebral damage.

Smoking is a major risk factor associated with perioperative respiratory and cardiovascular complications. Evidence also suggests that cigarette smoking causes imbalance in the prostaglandins and promotes vasoconstriction and excessive platelet aggregation. Two of the constituents of cigarette smoke, nicotine and carbon monoxide, have adverse cardiovascular effects. Carbon monoxide increases the incidence of arrhythmias and has a negative ionotropic effect both in animals and humans.

Smoking causes an increase in carboxyhaemoglobin levels, resulting in a leftward shift in which appears to represent a risk factor for some of these cardiovascular complications.

There are two mechanisms responsible for the leftward shift of oxyhaemoglobin dissociation curve when carbon monoxide is present in the blood. Carbon monoxide has a direct effect on oxyhaemoglobin, causing a leftward shift of the oxygen dissociation curve, and carbon monoxide also reduces the formation of 2,3-DPG by inhibiting glycolysis in the erythrocyte. Nicotine, on the other hand, has a stimulatory effect on the autonomic nervous system. The effects of nicotine on the cardiovascular system last less than 30 min.

The derived unit of energy, work or amount of heat is joule (J). It is defined as the amount of energy expended if a force of one newton (N) is applied through a distance of one metre (N·m)

J = 1 kg·m/s2·m = 1 kg·m2/s2 or 1 kg·m2·s-2

Kinetic energy (KE) = ½ MV2

An object with a mass of 1500 kg moving at 30 m/s correlates to 675 kJ:

KE = ½ (1500) × (30)2 = 750 × 900 = 675 kJ

Total energy released when 1 kg fat is metabolised to CO2 and water is 37 MJ. 1 g fat produces 37 kJ/g, therefore 1 kg fat produces 37,000 × 1000 = 37 MJ.

Raising the temperature of 1 kg water from 0°C to 100°C correlates to 420 kJ. The amount of energy needed to change the temperature of 1 kg of the substance by 1°C is the specific heat capacity. We have 1 kg water therefore:

4,200 J × 100 = 420,000 J = 420 kJ

In order to calculate the energy involved in raising a 100 kg mass to a height of 1 km against gravity, we need to calculate the potential energy (PE) of the mass:

PE = mass × height attained × acceleration due to gravity
PE = 100 kg × 1000 m × 10 m/s2 = 1 MJ

The heat generated when a direct current of 10 amps flows through a heating element for 10 seconds when the potential difference across the element is 1000 volts can be calculated by applying Joule’s law of heating:

Work done (WD) = V (potential difference) × I (current) × t (time)
WD = 10 × 10 × 1000 = 100 kJ