The number of osmoles (Osm) of solute per litre (L) of solution (Osmol/L) is the unit of measurement for solute concentration. The calculated serum osmolality assumes that the primary solutes in the serum are sodium salts (chloride and bicarbonate), glucose, and urea nitrogen.

2 (Na + K) + Glucose + Urea (all in mmol/L) = calculated osmolarity

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

Sodium and potassium ions clearly contribute the most to plasma osmolarity. Glucose and urea, on the other hand, are less so.

The osmolarity of normal serum is 285-295 mOsm/L. Temperature and pressure affect osmolality, and this calculated variable is less than osmolality for a given solution.

The number of osmoles (Osm) of solute per kilogramme (Osm/kg) is a measure of osmolality, which is also a measure of solute concentration. Temperature and pressure have no effect on the value. An osmometer is used to measure it in the lab. Osmometers rely on a solution’s colligative properties, such as a decrease in freezing point or a rise in vapour pressure.

The osmolar gap (OG) is calculated as follows:

OG = osmolaRity calculated from measured serum osmolaLity

Excess alcohols, lipids, and proteins in the blood can all contribute to the difference.

Glucose transport is a highly regulated process accomplished mostly by facilitated diffusion using carrier proteins to cross cell membranes.

There are many transporters, but the most important are known as glucose transporters (GLUTs).

Stresses in various form of acute and chronic forms affect the activity of glucose transporters.
They are responsive to many types of metabolic stress, including hypoxia, injury, hypoglycaemia, numerous metabolic inhibitors, stress hormones, and other influences such as growth factors.

Numerous signalling pathways appear to be involved in transporter regulation.

New evidence suggests that stresses regulating GLUTs are not only acute biological stresses. In addition, chronic low-grade inflammation, and their associated chronic diseases also lead to altered glucose transport. These include obesity, type 2 diabetes, cardiovascular disease, and the growth and spread of many tumours that are affected by altered glucose transporters. Some of these glucose transport effects are compensatory, while others are pathogenic.

Ultimately, deliberate manipulation of GLUTs could be used as treatment for some of these chronic diseases.

Such a high rise of end-tidal CO2 (EtCO2) in a patient who is spontaneously breathing is often encountered.

Close observation should occur for further rises in EtCO2 and other signs of malignant hyperthermia. If this were to rise even more, it might be wise to ensure that ventilatory support is available.

A lot would depend on whether surgery was almost completed. At this stage of anaesthesia, it would be inappropriate to administer opioid antagonists or respiratory stimulants.

The oxygen consumption rate (VO2) at rest is 3.5 ml/kg/minute (one metabolic equivalent or 1 MET).
3.86 ml/kg/minute thyrotoxicosis

Young children consume a lot of oxygen: around 7 ml/kg/min when they are born. The metabolic cost of breathing is higher in children than in adults, and it can account for up to 15% of total oxygen consumption. Similarly, an infant’s metabolic rate is nearly twice that of an adult, resulting in a larger alveolar minute volume and a lower FRC.

At term, oxygen consumption at rest can increase by as much as 40% (5 ml/kg/minute) and can rise to 60% during labour.

When compared to normal basal metabolism, sepsis syndrome increases VO2 and resting metabolic rate by 30% (4.55 ml/kg/minute). In septicaemic shock, VO2 decreases.

Dobutamine hydrochloride was infused into 12 healthy male volunteers at a rate of 2 micrograms per minute per kilogramme, gradually increasing to 4 and 6 micrograms per minute per kilogramme. Dobutamine was infused for 20 minutes for each dose. VO2 increased by 10% to 15%. (3.85-4.0 ml/kg/min).

The ‘ideal’ alveolar PO2 minus arterial PO2 is the alveolar-arterial (A-a) oxygen difference.

The ‘ideal’ alveolar PO2 is derived from the alveolar air equation and is the PO2 that the lung would have if there was no ventilation-perfusion (V/Q) inequality and it was exchanging gas at the same respiratory exchange ratio as real lung.

The amount of oxygen in the blood is measured directly in the arteries.

The A-a oxygen difference (or gradient) is a useful measure of shunt and V/Q mismatch, and it is less than 2 kPa in normal adults breathing air (15 mmHg). Because the shunt component is not corrected, the A-a difference increases when breathing 100 percent oxygen, and it can be up to 15 kPa (115 mmHg).

An abnormally low or abnormally high V/Q ratio within the lung can cause an increased A-a difference, though the former is more common. Atelectasis, which results in a low V/Q ratio, is the most likely cause of an A-a difference in a healthy adult breathing 100 percent oxygen.

Hypoventilation may cause an increase in alveolar (and thus arterial) CO2, lowering alveolar PO2 according to the alveolar air equation.

The alveolar PO2 is also reduced at high altitude.

Healthy people are unlikely to have a right-to-left shunt or an oxygen transport diffusion defect.

During glycolysis, 2,3-diphosphoglycerate (2,3-DPG) is
created in erythrocytes by the Rapoport-Luebering shunt.

The production of 2,3-DPG increases for several conditions
in the presence of decreased peripheral tissue O2 availability.
Some of these conditions include hypoxaemia, chronic lung
disease anaemia, and congestive heart failure. Thus,
2,3-DPG production is likely an important adaptive mechanism.

High levels of 2,3-DPG cause a shift of the curve to the right.
Low levels of 2,3-DPG cause a shift of the curve to the left,
as seen in states such as septic shock and hypophosphatemia.

The following table shows the compartments and their relative oxygen reserve:
Compartment Factors Room air (mL) 100% O2 (mL)
Lung FAO2, FRC 630 2850
Plasma PaO2, DF, PV 7 45
Red blood cells Hb, TGV, SaO2 788 805
Myoglobin 200 200
Interstitial space 25 160

Oxygen reserves in the body, with room air and after oxygenation.

FAO2-alveolar fraction of oxygen rises to 95% after administration of 100% oxygen (CO2 = 5%)
FRC- Functional residual capacity – (the most important store of oxygen in the body) – 2,500-3,000 mL in medium sized adults
PaO2-partial pressure of oxygen dissolved in arterial blood (80 mmHg breathing room air and 500 mmHg breathing 100% oxygen)
DF -dissolved form (0.3%)
PV-plasma volume (3L)
TG-total globular volume (5L)
Hb-haemoglobin concentration
SaO2-arterial oxygen concentration (98% breathing air and 100% when preoxygenated)

For estimating a child’s weight, the Resuscitation Council (UK) and European Resuscitation Council teach the following formula:

Weight = (age + 4) × 2

The weight of the child will be around 20 kg.

This formula is used in the Primary FRCA exam by the Royal College of Anaesthetists.

In ‘developed’ countries, the traditional ‘APLS formula’ for estimating weight in children based on age (wt in kg = [age+4] x 2) is acknowledged as underestimating weight by 33.4 percent on average, with the degree of underestimation increasing with increasing age.

However, more recently, the APLS formula ‘Weight=3(age)+7’ has been found to provide a mean underestimate of only 6.9%. This formula is applicable to children aged 1 to 13 years.

The estimated weight based on age using this formula is 25 kg.

This scenario describes rebreathing management.

Changes is exhaustion of the soda lime and a progressive rise in circuit deadspace is the most likely explanation for the capnograph.

It is important that the soda lime canister is inspected for a change in colour of the granules. Initially fresh gas flow should be increased and then if necessary, replace the soda lime granules. Other strategies include changing to another circuit or bypassing the soda lime canister after the fresh gas flow is increased.

Any other causes of increased equipment deadspace should be excluded.

Intraoperative hypercarbia can be caused by:

1. Hypoventilation – Breathing spontaneously; drugs which include anaesthetic agents, opioids, residual neuromuscular blockade, pre-existing respiratory or neuromuscular disease and cerebrovascular accident.
2. Controlled ventilation- circuit leaks, disconnection, miscalculation of patient’s minute volume.
3. Rebreathing – Soda lime exhaustion with circle, inadequate fresh gas flow into Mapleson circuits, increased breathing system deadspace.
4. Endogenous source – Tourniquet release, hypermetabolic states (MH or thyroid storm) and release of vascular clamps.
5. Exogenous source – Absorption of CO2 absorption from the pneumoperitoneum.

A decrease in the functional residual capacity (FRC) is the most important physiologic change to consider for such patients.

FRC is the sum of the expiratory reserve volume and the residual volume. It is the resting volume of the lung, and is an important marker for lung function. During this time, the alveolar pressure is equal to the atmospheric pressure. When morbidly obese individuals lie supine, the FRC decreases by as much as 40% because the abdominal contents push the diaphragm into the thoracic cavity.

Chest wall compliance is expected to reduce because of fat deposition surrounding adjacent structures.

Inspiratory reserve volume (IRV) is expected to increase, and peak expiratory flow is expected to decrease, however the decrease in FRC is more important to consider because of the risk of hypoxia secondary to premature airway closure and ventilation-perfusion mismatch.

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.

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

If there is no change in preload and myocardial contractility, there will be decrease in end-diastolic volume and stroke volume. So there must be increase in end-systolic volume.

In contrast to the arterial system, which contains 15% of the circulating blood volume, the body’s veins contain 70% of it.

In severe haemorrhage, when sympathetic stimulation causes venoconstriction, venous tone is important in maintaining the return of blood to the heart.

Because the liver receives about 30% of the resting cardiac output, it is a very vascular organ. The hepatic vascular system is dynamic, which means it can store and release blood in large amounts – it acts as a reservoir within the general circulation.

In a normal situation, the liver contains 10-15% of total blood volume, with the sinusoids accounting for roughly 60% of that. The liver dynamically adjusts its blood volume when blood is lost and can eject enough blood to compensate for a moderate amount of haemorrhage.

In the portal venous and hepatic arterial systems, sympathetic nerves constrict the presinusoidal resistance vessels. More importantly, sympathetic stimulation lowers the portal system’s capacitance, allowing blood to flow more efficiently to the heart.

Net transcapillary absorption of interstitial fluid from skeletal muscle into the intravascular space compensates for blood loss effectively during haemorrhage. The decrease in capillary hydrostatic pressure (Pc), caused by reflex adrenergic readjustment of the ratio of pre- to postcapillary resistance, is primarily responsible for fluid absorption. Within a few hours of blood loss, these fluid shifts become significant, further diluting haemoglobin and plasma proteins.

Albumin synthesis begins to increase after 48 hours.

The juxtamedullary complex releases renin in response to a drop in mean arterial pressure, which causes an increase in aldosterone level and, eventually, sodium and water resorption. Increased antidiuretic hormone (ADH) levels also contribute to water retention.

The cardiac action potential has several phases which have different mechanisms of action as seen below:
Phase 0: Rapid depolarisation – caused by a rapid sodium influx.
These channels automatically deactivate after a few ms

Phase 1: caused by early repolarisation and an efflux of potassium.

Phase 2: Plateau – caused by a slow influx of calcium.

Phase 3 – Final repolarisation – caused by an efflux of potassium.

Phase 4 – Restoration of ionic concentrations – The resting potential is restored by Na+/K+ATPase.
There is slow entry of Na+into the cell which decreases the potential difference until the threshold potential is reached. This then triggers a new action potential

Of note, cardiac muscle remains contracted 10-15 times longer than skeletal muscle.

Different sites have different conduction velocities:
1. Atrial conduction – Spreads along ordinary atrial myocardial fibres at 1 m/sec

2. AV node conduction – 0.05 m/sec

3. Ventricular conduction – Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec, the fastest conduction in the heart. This allows a rapid and coordinated contraction of the ventricles

The respiratory quotient is the ratio of CO2 produced to O2 consumed while food is being metabolized:

RQ = CO2 eliminated/O2 consumed

Most energy sources are food containing carbon, hydrogen and oxygen. Examples include fat, carbohydrates, protein, and ethanol. The normal range of respiratory coefficients for organisms in metabolic balance usually ranges from 1.0-0.7.

Granulated sugar is a refined carbohydrate with no significant fat, protein or ethanol content.

The RQ for carbohydrates is = 1.0

The RQ for the rest of the compounds are:

Fats RQ = 0.7
The chemical composition of fats differs from that of carbohydrates in that fats contain considerably fewer oxygen atoms in proportion to atoms of carbon and hydrogen.

Protein RQ = 0.8
Due to the complexity of various ways in which different amino acids can be metabolized, no single RQ can be assigned to the oxidation of protein in the diet; however, 0.8 is a frequently utilized estimate.

The pH of CSF is 7.31 which is lower than plasma.

Compared to plasma, it has a lower concentration of potassium, calcium, and protein and a higher concentration of sodium, chloride, bicarbonate and magnesium.

CSF usually has no cells present but if white cells are present, there should be no more than 4/ml.

The pressure of CSF should be less than 20 cm of water.

The concentration of glucose is approximately two-thirds of that of plasma, and it has a concentration of approximately 3.3-4 mmol/L.

PaCO2 is one of the most important factors that regulate cerebral vascular tone. CO2 induces cerebral vasodilatation and as a result, it increases CBF. Between 20 mmHg (2.7 kPa) and 80 mmHg (10.7 kPa), there is a linear increase of PaCO2.

Sometimes, there are areas where auto regulation has failed locally but not globally. Similarly, local vs. systemic acidosis will have similar effects. When the PaO2 falls below 50 mmHg (6.5 kPa), the CBF progressively increases.

An increase in the cerebral metabolic rate for oxygen (CMRO2) and therefore CBF can be caused by hyperthermia.
A late feature of cerebral injury is hyperthermia secondary to hypothalamic injury. Therefore this is not the most likely cause of an increased CBF in this scenario.

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.

Awareness during general anaesthesia is a frightening experience, which may result in serious emotional injury and post-traumatic stress disorder.

The incidence of awareness during general anaesthesia with current anaesthetic agents and techniques has been reported as 0.2-0.4% in nonobstetric and noncardiac surgery, as 0.4% during caesarean section, and as 1.5% in cardiac surgery.

The incidence during major trauma surgery is higher. Incidence of recall has been reported to be as high as 11-43% in major trauma cases.

1% solution contains 1 g of substance per 100 mL.

A solution of 10% glucose is 10 g/100mL. Therefore 1000 mL of this glucose solution will contain 100 g.

1 g of glucose yields about 4 kcal of energy. One litre of 10% glucose will therefore release approximately 4x100g = 400 kcal of energy.

A solution of 20% fat is 20 g/100mL. Therefore 1000 mL of this fat solution will have 200 g and 500 mL will contain 100 g.

1 g of fat yields approximately 9 kcal. 500 mL of 20% fat therefore has the potential to yield 900 kcal of energy.

The total energy input over this 24 hour period is approximately 400kcal + 900kcal = 1300 kcal.

Second messengers relay signals to target molecules in the cytoplasm or nucleus when an agonist interacts with a receptor on the cell surface. They also amplify the strength of the signal. The most ubiquitous and abundant second messenger is calcium and it regulates multiple cellular functions in the body.

These include:
Muscle contraction (skeletal, smooth and cardiac)
Exocytosis (neurotransmitter release at synapses and insulin secretion)
Apoptosis
Cell adhesion to the extracellular matrix
Lymphocyte activation
Biochemical changes mediated by protein kinase C.

cAMP is either inhibited or stimulated by G proteins.

The receptors in the body that stimulate G proteins and increase cAMP include:

Beta (?1, ?2, and ?3)
Dopamine (D1 and D5)
Histamine (H2)
Glucagon
Vasopressin (V2).

The second messenger for the action of nitric oxide (NO) and atrial natriuretic peptide (ANP) is cGMP.

The second messengers for angiotensin and thyroid stimulating hormone are inositol triphosphate (IP3) and diacylglycerol (DAG).

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.

For the local anaesthetic base to be stable in solution, it is formulated as a hydrochloride salt. As such, the molecules exist in a quaternary, water-soluble state at the time of injection. However, this form will not penetrate the neuron. The time for onset of local anaesthesia is therefore predicated on the proportion of molecules that convert to the tertiary, lipid-soluble structure when exposed to physiologic pH (7.4).

The ionization constant (pKa) for the anaesthetic predicts the proportion of molecules that exists in each of these states. By definition, the pKa of a molecule represents the pH at which 50% of the molecules exist in the lipid-soluble tertiary form and 50% in the quaternary, water-soluble form. The pKa of all local anaesthetics is >7.4 (physiologic pH), and therefore a greater proportion the molecules exists in the quaternary, water-soluble form when injected into tissue having normal pH of 7.4.

Furthermore, the acidic environment associated with inflamed tissues favours the quaternary, water-soluble configuration even further. Presumably, this accounts for difficulty when attempting to anesthetize inflamed or infected tissues; fewer molecules exist as tertiary lipid-soluble forms that can penetrate nerves.

After a paediatric case, you’ll frequently have to calculate and prescribe maintenance fluids. The ‘4-2-1 rule’ should be used as a guideline:

1st 10 kg – 4 ml/kg/hr
2nd 10 kg – 2 ml/kg/hr
Subsequent kg – 1 ml/kg/hr

Hence

1st 10 kg = 4 × 10 = 40 ml
2nd 10 kg = 2 × 10 = 20 ml
Subsequent kg = 1 × 1 = 1 ml
Total = 61 ml/hr

61 × 12 = 732 ml over 12 hrs.

For this patient, his forced expiratory volume in 1 second (FEV1) will decrease at the same rate as a non-smoker.

There is a notable, but slow, decline in FEV1 when an individual reaches the age of 26. An average reduction of 30 mls every year in non-smokers, while a more significant reduction of 50-70 mls is observed in approximately 20% of smokers.

Considering the age of the patient, individuals who begin smoking cessation by the age of 60 are far less likely to achieve normal FEV1 levels, even in the next five years. It is expected that their FEV1 will be approximately 14% less than their peers of the same age.

The commonest and most likely cause of a gradual rise in end-tidal CO2 (EtCO2) occurring during anaesthesia in a spontaneously breathing patient is hypoventilation. This occurs from the respiratory depressant effects of the opioid and sevoflurane.

Malignant hyperthermia should be sought if the EtCO2 shows further progressive rise.

Causes of rebreathing and a rise in the baseline of the capnograph can be caused by exhausted soda lime and inadequate fresh gas flow into the Bain circuit.

A sudden rise in EtCO2 can be caused deflation of the tourniquet.

Human skeletal muscle is composed of a heterogeneous collection of muscle fibre types which differ histologically, biochemically and physiologically.

It can be biochemically classified into 2 groups. This is based on muscle fibre myosin ATPase histochemistry. These are:

Type 1 (slow twitch): Muscle fibres depend upon aerobic glycolytic metabolism and aerobic oxidative metabolism. They are rich in mitochondria, have a good blood supply, rich in myoglobin and are resistant to fatigue.

Type II (fast twitch): Muscle fibres are sub-divided into:
Type IIa – relies on aerobic/oxidative metabolism
Type IIb – relies on anaerobic/glycolytic metabolism.

Fast twitch muscle fibres produce short bursts of power but are more easily fatigued.

Cardiac and smooth muscle twitches are relatively slow compared with skeletal muscle.

The response of cerebral blood flow (CBF) to hyperoxia (PaO2 >15 kPa, 113 mmHg), the cerebral oxygen vasoreactivity is less well defined. A study originally described, using a nitrous oxide washout technique, a reduction in CBF of 13% and a moderate increase in cerebrovascular resistance in subjects inhaling 85-100% oxygen. Subsequent human studies, using a variety of differing methods, have also shown CBF reductions with hyperoxia, although the reported extent of this change is variable. Another study assessed how supra-atmospheric pressures influenced CBF, as estimated by changes in middle cerebral artery flow velocity (MCAFV) in healthy individuals. Atmospheric pressure alone had no effect on MCAFV if PaO2 was kept constant. Increases in PaO2 did lead to a significant reduction in MCAFV; however, there were no further reductions in MCAFV when oxygen was increased from 100% at 1 atmosphere of pressure to 100% oxygen at 2 atmospheres of pressure. This suggests that the ability of cerebral vasculature to constrict in response to increasing partial pressure of oxygen is limited.

Increases in arterial blood CO2 tension (PaCO2) elicit marked cerebral vasodilation.

CBF increases with general anaesthesia, ketamine anaesthesia, and hypoviscosity.

The basal metabolic rate (BMR) is the amount of energy required to maintain basic bodily functions in the resting state. The unit is Watt (Joule/second) or calories per unit time.

Indirect calorimetry measures O2 consumption and CO2 production where gases are collected in a canopy which is the gold standard, Douglas bag, face-mask dilution technique or interfaced with a ventilator.

The BMR can be calculated using the Weir formula:

Metabolic rate (kcal per day) = 1.44 (3.94 VO2 + 1.11 VCO2)

The BMR should be measured while lying down and at rest with the following conditions met:

It should follow a 12 -hour fast
No stimulants ingested within a 12-hour period
It should be done in a neutral thermal environment (between 20°C-25°C)