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.

A preplanned preinduction strategy includes the consideration of various interventions designed to facilitate intubation should a difficult airway occur. Non-invasive interventions intended to manage a difficult airway include, but are not limited to: (1) awake intubation, (2) video-assisted laryngoscopy, (3) intubating stylets or tube-changers, (4) SGA for ventilation (e.g., LMA, laryngeal tube), (5) SGA for intubation (e.g., ILMA), (6) rigid laryngoscopic blades of varying design and size, (7) fibreoptic-guided intubation, and (8) lighted stylets or light wands.

Most supraglottic airway devices (SADs) are designed for use during routine anaesthesia, but there are other roles such as airway rescue after failed tracheal intubation, use as a conduit to facilitate tracheal intubation and use by primary responders at cardiac arrest or other out-of-hospital emergencies. Supraglottic airway devices are intrinsically more invasive than use of a facemask for anaesthesia, but less invasive than tracheal intubation. Supraglottic airway devices can usefully be classified as first and second generation SADs and also according to whether they are specifically designed to facilitate tracheal intubation. First generation devices are simply ‘airway tubes’, whereas second generation devices incorporate specific design features to improve safety by protecting against regurgitation and aspiration.

The half life of Retinol binding protein (RBP) is 10-12 hours and therefore reflects more acute changes in protein metabolism than any of these proteins. Therefore it is not commonly used as a parameter for nutritional assessment.

The half life of Transthyretin (thyroxine binding pre-albumin) is only one to two days and so levels are less sensitive and this protein is not an albumin precursor. 15 mg/dL represents early malnutrition and a need for nutritional support.

Albumin levels have been frequently as a marker of nutrition but this is not a very sensitive marker. It’s half life more than 30 days and significant change takes some time to be noticed. Also, synthesis of albumin is decreased with the onset of the stress response after burns. Unrelated to nutritional status, the synthesis of acute phase proteins increases and that of albumin decreases.

A more accurate indicator of protein stores is transferrin. It’s response to acute changes in protein status is much faster. The half life of serum transferrin is shorter (8-10 days) and there are smaller body stores than albumin. A low serum transferrin level is below 200 mg/dL and below 100 mg/dL is considered severe. Serum transferrin levels can also affect serum transferrin level.

Fibronectin is used a nutritional marker but levels decrease after seven days of starvation. It is a glycoprotein which plays a role in enhancing the phagocytosis of foreign particles.

Carbonic anhydrase is an enzyme which contains zinc and can be found in:
1. Erythrocytes
2. Pulmonary endothelium
3. The intestine
4. Pancreas
5. Cardiac muscle and skeletal muscle.

To date, there have been seven isoenzymes identified. Of note, isoenzyme IV is found in the brush border of the proximal convoluted tubule and isoenzyme II is found within the luminal cells.

Acetazolamides a carbonic anhydrase inhibitor and is used as prophylaxis against mountain sickness and in glaucoma management.

Spironolactone is a potassium diuretic and is an aldosterone antagonist.

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).

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.

Compliance of the respiratory system describes the expandability of the lungs and chest wall. There are two types of compliance: dynamic and static.

Dynamic compliance describes the compliance measured during breathing, which involves a combination of lung compliance and airway resistance. Defined as the change in lung volume per unit change in pressure in the presence of flow.

Static compliance describes pulmonary compliance when there is no airflow, like an inspiratory pause. Defined as the change in lung volume per unit change in pressure in the absence of flow.

For example, if a person was to fill the lung with pressure and then not move it, the pressure would eventually decrease; this is the static compliance measurement. Dynamic compliance is measured by dividing the tidal volume, the average volume of air in one breath cycle, by the difference between the pressure of the lungs at full inspiration and full expiration. Static compliance is always a higher value than dynamic

Static compliance can be computed using the formula:

Cstat = Tidal volume/Plateau pressure – PEEP

Substituting the values given,

Cstat = 800/50-10
Cstat = 20 ml/cmH2O

The patient in the case has a fluid volume requirement of 30 mL/kg/day. His basic electrolyte requirement per day is:

Sodium at 2 mmol/kg/day x 110 = 220 mmol/day
Potassium at 1 mmol/kg/day x 110 = 110 mmol/day

His energy requirement per day is:

35 kcal/kg/day x 110 kg = 3850 kcal/day

One gram of glucose in fluid can provide approximately 4 kilocalories.

The following are the electrolyte components of the different intravenous fluids:

Fluid Na (mmol/L) K (mmol/L)
0.9% Normal saline (NSS) 154 0
0.45% NSS + 5% dextrose 77 0
0.18% NSS + 4% dextrose 30 0
Hartmann’s 131 5
5% dextrose 0 0

1000 mL of 5% dextrose has 50 g of glucose

Option B is inadequate for his sodium and caloric requirements (30 mmol of Na+ and 560 kcal). It is adequate for his K+ requirement (120 mmol of K+).

Option C is in excess of his Na+ requirement (462 mmol of Na+). Moreover, it does not provide any K+ replacement.

Option D is inadequate for his caloric requirement (600 kcal) and K+ requirement (60 mmol of K+). Moreover it does not provide any Na+ replacement.

Option E is in excess of his Na+ requirement (393 mmol of Na+), and is inadequate for his potassium requirement (15 mmol of K+)

Option A has adequate amounts for his Na+ (231 mmol of Na+) and K+ (120 mmol of K+) requirements. It is inadequate for his caloric requirement (600 kcal).

The following is the Advanced Trauma Life Support (ATLS) classification of haemorrhagic shock:

Class I haemorrhage:
It has blood loss up to 15%. There is very less tachycardia, and no changes in blood pressure, RR or pulse pressure. Usually, fluid replacement is not required.

Class II haemorrhage:
It has 15-30% blood loss, equivalent to 750 – 1500 ml. There is tachycardia, tachypnoea and a decrease in pulse pressure. Patient may be frightened, hostile and anxious. It can be stabilised by crystalloid and blood transfusion.

Class III haemorrhage:
There is 30-40% blood loss. It portrays inadequate perfusion, marked tachycardia, tachypnoea, altered mental state and fall in systolic pressure. It requires blood transfusion.

Class IV haemorrhage:
There is > 40% blood volume loss. It is a preterminal event, and the patient will die in minutes. It portrays tachycardia, significant depression in systolic pressure and pulse pressure, altered mental state, and cold clammy skin. There is need for rapid transfusion and surgical intervention.

Krebs’ cycle (tricarboxylic acid cycle or citric acid cycle) is a sequence of reactions to release stored energy through oxidation of acetyl coenzyme A (acetyl-CoA). Some of the products are carbon dioxide and hydrogen atoms.

The sequence of reactions, known collectively as oxidative phosphorylation, only occurs in the mitochondria (not cytoplasm).

The Krebs cycle can only take place when oxygen is present, though it does not require oxygen directly, because it relies on the by-products from the electron transport chain, which requires oxygen. It is therefore considered an aerobic process. It is the common pathway for the oxidation of carbohydrate, fat and some amino acids, required for the formation of adenosine triphosphate (ATP).

Pyruvate enters the mitochondria and is converted into acetyl-CoA. Acetyl-CoA is then condensed with oxaloacetate, to form citrate which is a six carbon molecule. Citrate is subsequently converted into isocitrate, alpha-ketoglutarate, succinyl-CoA, succinate, fumarate, malate and finally oxaloacetate.

The only five carbon molecule in the cycle is Alpha-ketoglutarate.