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)

The cervical plexus is a complex network of nerves within the head and neck region, providing nerve innervation to regions within the head, neck and trunk.

It is comprised of nerves arising from the anterior primary rami of the C1-C4 nerve roots.

The cervical plexus gives off superficial and deep branches. The superficial branches penetrate through the deep fascia at the centre point of the posterior border of the sternocleidomastoid. It provides sensory innervation from the lower border of the mandible to the 2nd rib. The deep branches provide motor innervation to the neck and diaphragmatic muscles.

Cervical plexus block is surgically relevant as it is used to provide regional anaesthesia for procedures in the neck region. The anaesthesia should be injected into the centre point of the posterior border of the sternocleidomastoid. Complications arise when anaesthesia is instead injected into the wrong point, including into the vertebral artery, subarachnoid and epidural spaces, blockade of phrenic and recurrent laryngeal nerves, and the cervical sympathetic plexus.

The option that is most responsible is the progressive decrease in venous return of blood to the right atrium. The heart rate does not usually change with PEEP so the fall in cardiac output is due to a reduction in left ventricular (LV) stroke volume (SV).

Note that the interventricular septum does shift toward the left and there is an increased pulmonary vascular resistance (PVR) from overdistention of alveolar air sacs that contribute to the reduction in cardiac output. Any increase in PVR will be associated with reduced pulmonary vascular capacitance.

The ventilation/perfusion ratio varies in different areas of the lung. In an upright individual, although both ventilation and perfusion increase from the apex to the base of the lung, the increase in ventilation is less than the increase in blood flow. As a result, the normal V̇ /Q̇ ratio at the apex of the lung is much greater than 1 (ventilation exceeds perfusion), whereas the V̇ /Q̇ ratio at the base of the lung is much less than 1 (perfusion exceeds ventilation).

There is more volume in the alveoli found in the apices than in the bases of the lungs. This is due to the weight of the lung stretching the apical alveoli to the maximum size. Also, the weight of the lungs pull themselves away from the chest wall, creating a negative intrapleural pressure. These factors, however, do not directly affect the PAO2.

Giardiasis is known to have a longer incubation time and doesn’t cause bloody diarrhoea.

Cholera usually doesn’t cause bloody diarrhoea.

Generally, most of the E.coli strains do not cause bloody diarrhoea.

Diverticulitis can be a cause of bloody stool but the history here points out to an infectious cause.

Campylobacter infection is the most probable cause as it is characterized by a prodrome, abdominal pain and bloody diarrhoea

Potassium maintains the resting potential of cardiac myocytes, with depolarization triggered by a rapid influx of sodium ions, and repolarization due to efflux of potassium. A slow influx of calcium is responsible for the longer duration of a cardiac action potential compared with skeletal muscle.

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 operating theatre is an unusual place with several applications of electrical equipment to the human body. This can lead to potential dangers associated with it that need to be prevented. Electrical safety in the operation theatre is the understanding of how these potential dangers can occur and how they can be prevented.

Electricity can cause morbidity or mortality by one of the following ways:
(i) electrocution
(ii) burns
(iii) ignition of a flammable material, causing a fire or explosion.

Electrocution is dependant on factors like duration of contact with electric current, the current pathway and the frequency and size of current.

Option A: The higher the frequency, the less effects of electrocution on the body.

Option B & D: Equipment can be classified in classes and types.
The class designation describes the method used for protection against electrocution. Class I is basic protection, class II is double insulation and class III is safety extra low voltage.
The type designation describes the degree of protection based on the maximum permissible leakage currents under normal and fault conditions.
Type B:
can be class I, II or III but the maximum leakage current must not exceed 100 µA. It is therefore not suitable for direct connection to the heart.
Type BF
Similar to type B, but uses an isolated (or floating) circuit.
Type CF
Only type CF protect against microshock as they allow leakage currents of 0.05 mA per electrode for class I and 0.01 mA for class II. Microshock is a small leakage current that can cause harm because of direct connection to the heart via transvenous lines or wires, bypassing the impedance of the skin, leading to ventricular fibrillation. Microshock current of 100 ?A is sufficient to cause VF.

Option C: A 75mA electrocution can cause ventricular fibrillation. Use the following as a general guide to understand the effect of current size on the body.
1 mA – tingling pain
5 mA – pain
15 mA – tonic muscular contraction
50 mA – respiratory muscle paralysis
75 mA – ventricular fibrillation.

Option E: Wet skin reduces the resistance to current flow and therefore increases the effects of electrocution.

Drug interactions can be seen in the following examples:

Additive interaction (summation).

Additive effects are described for intravenous drug combinations such as ketamine and thiopentone or ketamine and midazolam. Different mechanisms of action are used by them. Thiopentone and midazolam are GABAA receptor agonists, whereas ketamine is an NMDA receptor antagonist. Nitrous oxide and halothane are two other examples.

Synergism is a supra-additive interaction.

Refers to the administration of two drugs with similar pharmacological properties and closely related sites of action, resulting in a combined effect that is greater than the sum of the contributions of each component. The construction of an isobologram can be used to interpret and understand these. The best example is the hypnotic effect of benzodiazepines and intravenous induction agents like propofol. As part of a co-induction technique, midazolam is frequently given before propofol.

Potentiation

In a dose-dependent manner, volatile agents enhance the effects of neuromuscular blocking agents. Electrolyte disturbance (hypomagnesaemia), Penicillin, and probenecid can all increase the effects of neuromuscular blocking agents (the latter has no similar pharmacological activity).

Infra-additive interaction (antagonism).

This can be subdivided into the following categories:

-Pharmacokinetic interference occurs when one drug affects the absorption of another through the gastrointestinal tract or when hepatic microsomal enzyme induction influences metabolism.
-Heparin and protamine, for example, or heavy metals and chelating agents, are examples of chemical antagonists.
-Competitive reversible antagonistic antagonism of receptors, such as opioids and naloxone, and irreversible antagonistic antagonism of receptors

Oxytocin is secreted by the posterior pituitary along with Antidiuretic Hormone (ADH). It increases the contraction of the upper segment (fundus and body) of the uterus whereas the lower segment is relaxed facilitating the expulsion of the foetus.

Oxytocin acts through G protein-coupled receptor and phosphoinositide-calcium second messenger system to contract uterine smooth muscle.

It has 0.5 to 1 % ADH activity introducing possibilities of water intoxication when used in high doses.

The sensitivity of the uterus to oxytocin increases as the pregnancy progresses.

It is used for induction of labour in post maturity and uterine inertia.

A is correct. Common myeloid progenitor cells are involved in the anaphylaxis reaction.
B is incorrect. The common lymphoid lineage gives rise to T-cells, B-cell and NK cells.
C is incorrect as megakaryocytes give rise to platelets.
D is incorrect – Neural crest cells give rise to various cells throughout the body, including melanocytes, enterochromaffin cells and Schwann cells. However, they do not give rise to mast cells.
E is incorrect. Reticulocytes give rise to erythrocytes.

This is a classic case of anaphylaxis. In this situation, IgE previously raised against antigens (in this case peanut antigen) bind to mast cells, and this causes them to degranulate.
There is release of vasoactive substances like histamine into the blood, and this is responsible for the symptoms seen. Therefore, the main type of cells involved in the pathogenesis of the disease is mast cells.

Even though aprotinin reduces fibrinolysis and therefore bleeding, there is an associated increased risk of death. It was withdrawn in 2007.
Protein C is dependent upon vitamin K and this may paradoxically increase the risk of thrombosis during the early phases of warfarin treatment.

The coagulation cascade include two pathways which lead to fibrin formation:
1. Intrinsic pathway – these components are already present in the blood
Minor role in clotting
Subendothelial damage e.g. collagen
Formation of the primary complex on collagen by high-molecular-weight kininogen (HMWK), prekallikrein, and Factor 12
Prekallikrein is converted to kallikrein and Factor 12 becomes activated
Factor 12 activates Factor 11
Factor 11 activates Factor 9, which with its co-factor Factor 8a form the tenase complex which activates Factor 10

2. Extrinsic pathway – needs tissue factor that is released by damaged tissue)
In tissue damage:
Factor 7 binds to Tissue factor – this complex activates Factor 9
Activated Factor 9 works with Factor 8 to activate Factor 10

3. Common pathway
Activated Factor 10 causes the conversion of prothrombin to thrombin and this hydrolyses fibrinogen peptide bonds to form fibrin. It also activates factor 8 to form links between fibrin molecules.

4. Fibrinolysis
Plasminogen is converted to plasmin to facilitate clot resorption

Silent (S) is the most probable phenotype of the patient. In S phenotype, patients have significantly reduced levels of BChE, the lowest among the four phenotypes. Because of this, individuals with S phenotype are subjected to long periods of apnoea. In addition, their dibucaine number is very low.

Other BChE phenotypes are the following:

Usual (U)
Atypical (A)
Fluoride-resistant (F)

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.

The ions found in higher concentrations intracellularly than outside the cells are:

ATP
AMP
Potassium
Phosphate, and
Magnesium Adenosine diphosphate (ADP)

Sodium is a primarily extracellular ion.

Propofol is considered a safe drug to use in porphyria because even if causes mild elevation of porphyrins inpatient, it does not cause any symptoms.

Since barbiturates are inducers of ALA synthetase, they are contraindicated in porphyria patients. So, thiopentone most not be used.

Etomidate is a potent inhibitor of adrenal 11 beta-hydroxylase and 17 alpha-hydroxylase reducing cortisol and aldosterone synthesis in the adrenal cortex and has been associated with exacerbations of porphyria in animal studies and it is advisable not to use it in this condition.

Ketamine should be reserved for the hemodynamically unstable patient, however, it is a safe drug.

Diazepam is safe in porphyria but is not usually used for a rapid sequence induction.

Based on the presenting symptoms and clinical examination, it is a case of an adult sinus bradycardia with adverse signs. The first pharmacological treatment for this condition is atropine 500mcg intravenously and if necessary repeat every three to five minutes up to a maximum of 3 mg.

If the bradycardia does not subside even after the administration of atropine, cardiac pacing should be considered. If pacing cannot be achieved promptly, we should consider the use of second-line drugs like adrenaline, dobutamine, or isoprenaline.

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

Continuous closure of the vocal cords resulting in partial or complete airway obstruction is called Laryngospasm. It is a reflex that helps protect against pulmonary aspiration.

Predisposing factors include: Hyperactive airway disease, Insufficient depth of anaesthesia, Inexperience of the anaesthetist, Airway irritation, Smoking, Shared airway surgery and Paediatric patients

Its primary treatment includes checking for blood or stomach aspirate in the pharynx, removing any triggering stimulation, relieving any possible supra-glottic component to airway obstruction and application of CPAP with 100% oxygen.

In this patient, all the above has been done and the next treatment of choice is the administration of a rapidly acting intravenous anaesthetic agent such as propofol (0.5 mg/kg) in increments as it has been reported to relieve laryngospasm in approximately 75% of cases. Administering suxamethonium to an awake patient would be inappropriate at this stage.

Magnesium and lidocaine are used for prevention rather than acute treatment of laryngospasm. Superior laryngeal nerve blocks have been reported to successfully treat recurrent laryngospasm but it is not the next logical step in index patient.

Pipeline gases (in the UK this includes: Oxygen, Nitrous oxide, Medical air, and Entonox) are supplied at 4 bar (or 400 kPa), and compressed air is supplied at 7 bar for power tools.

Carbon dioxide and nitric oxide are usually only supplied in cylinders.

The intercostal nerves arise from the ventral rami of the first 11 thoracic spinal nerves. they course along the costal groove on the lower margin of the rib.

The twelfth intercoastal nerve is called the subcostal nerve. This is because it is below the 12th rib.

Each intercostal nerve is connected to a ganglion of the sympathetic trunk from which it carries preganglionic and postganglionic fibres that innervate blood vessels, sweat glands, and muscles.

The lateral and medial pectoral nerves innervates pectoralis major muscle.

The pH at which the drug exists in 50 percent ionised and 50 percent unionised forms is known as the pKa.

To calculate the proportion of ionised to unionised form of an ACID, use the Henderson-Hasselbalch equation.

pH = pKa + log ([A-]/[HA])

or

pH = pKa + log [(salt)/(acid)]
pH = pKa + log ([ionised]/[unionised]).

Hence, if the pKa − pH = 0, then 50% of drug is ionised and 50% is unionised.

In this example:

7.4 = 4.3 + log ([ionised]/[unionised])
7.4 − 4.3 = log ([ionised]/[unionised])
log 3.1 = log ([ionised]/[unionised])

Simply put, the antilog is the inverse log calculation. In other words, if you know the logarithm of a number, you can use the antilog to find the value of the number. The antilogarithm’s definition is as follows:

y = antilog x = 10x

Antilog to the base 10 of 0 = 1, 1 = 10, 2 =100, 3 = 1000, and 4 = 10,000.

If you want to find the antilogarithm of 3.1, for a number between 3 and 4, the antilogarithm will return a value between 1000 and 10,000. The ratio is 1:1 if pKa = pH, that is, pH pKa = log 0. (50 percent ionised and unionised).

According to the above value, there is only one unionised molecule for every approximately 1000 (1259) ionised molecules of this drug in plasma, implying that this drug is largely ionised in plasma (99.99 percent ).

Adenosine receptors are expressed on the surface of most cells.
Four subtypes are known to exist which are A1, A2A, A2B and A3.

Of these, the A1 and A2 receptors are present peripherally and centrally. There are agonists at the A1 receptors which are antinociceptive, which reduce the sensitivity to a painful stimuli for the individual. There are also agonists at the A2 receptors which are algogenic and activation of these results in pain.

The role of adenosine and other A1 receptor agonists is currently under investigation for use in acute and chronic pain states.

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.

ICP is significant because it influences cerebral perfusion pressure and cerebral blood flow. The normal ICP ranges from 5 to 13 mmHg.

The components within the skull include the brain (80%/1400 ml), blood (10%/150 ml), and cerebrospinal fluid (CSF) (10%/150 ml).

Because the skull is a rigid box, if one of the three components increases in volume, one or more of the remaining components must decrease in volume to compensate, or the ICP will rise (Monroe-Kellie hypothesis).

Primary brain injury occurs as a result of a head injury and is unavoidable unless precautions are taken to reduce the risk of head injury. A reduction in oxygen delivery due to hypoxemia (low arterial PaO2) or anaemia, a reduction in cerebral blood flow due to hypotension or reduced cardiac output, and factors that cause a raised ICP and reduced CPP are all causes of secondary brain injury. Secondary brain injury can be avoided with proper management.

The most important initial management task is to make certain that:

There is protection of the airway and the cervical spine
There is proper ventilation and oxygenation
Blood pressure and cerebral perfusion pressure are both adequate (CPP).

Following the implementation of these management principles, additional strategies to reduce ICP and preserve cerebral perfusion are required. The volume of one or more of the contents of the skull can be reduced using techniques that can be used to reduce ICP.

Reduce the volume of brain tissue
Blood volume should be reduced.
CSF volume should be reduced.

The following are some methods for reducing the volume of brain tissue:
Abscess removal or tumour resection
Steroids (especially dexamethasone) are used to treat oedema in the brain.
To reduce intracellular volume, use mannitol/furosemide or hypertonic saline.
To increase intracranial volume, a decompressive craniectomy is performed.

The following are some methods for reducing blood volume:

Haematomas must be evacuated.
Barbiturate coma reduces cerebral metabolic rate and oxygen consumption, lowering cerebral blood volume as a result.
Hypoxemia, hypercarbia, hyperthermia, vasodilator drugs, and hypotension should all be avoided in the arterial system.
PEEP/airway obstruction/CVP lines in neck: patient positioning with 30° head up, avoid neck compression with ties/excessive rotation, avoid PEEP/airway obstruction/CVP lines in neck

The following are some methods for reducing CSF volume:

To reduce CSF volume, an external ventricular drain or a ventriculoperitoneal shunt is inserted (although more a long term measure).

The gag reflex is a protective mechanism that prevents any foreign material to enter the aerodigestive tract.

This reflex has afferent (sensory) and effect (motor) components.
– Glossopharyngeal nerve form the afferent limb
– Vagus nerve form the efferent limb

Funnel plot is essentially a scatterplot of the effect of treatment against a particular measure of study precision. Its primal purpose is to serve as a visual aid and help in detection of bias or systematic heterogenity.

When responsiveness diminishes rapidly after administration of a drug, the response is said to be subject to tachyphylaxis. This may be due to frequent or continuous exposure to agonists, which often results in short-term diminution of the receptor response.

Many mechanisms may be responsible, such as blocking access of G protein to activated receptor, or receptor molecules internalized by endocytosis to prevent exposure to extracellular molecules.

Tolerance occurs when larger doses are required to produce the same effect. This may be due to changes in receptor number or function due to exposure to the drug.

Desensitization refers to the common situation where the biological response to a drug diminishes when it is given continuously or repeatedly. It is a chronic loss of response, occurring over a longer period than tachyphylaxis. It may be possible to restore the response by increasing the dose (or concentration) of the drug but, in some cases, the tissues may become completely refractory to its effect.

Drug dependence is defined as a psychic and physical state of the person characterized by behavioural and other responses resulting in compulsions to take a drug, on a continuous or periodic basis in order to experience its psychic effect and at times to avoid the discomfort of its absence.

With respect to oxygen transport in cells, almost all oxygen is transported within erythrocytes. There is limited solubility and only 1% is carried as solution. Thus, the amount of oxygen transported depends upon haemoglobin concentration and its degree of saturation.

Haemoglobin is a globular protein composed of 4 subunits. Haem is made up of a protoporphyrin ring surrounding an iron atom in its ferrous state. The iron can form two additional bonds – one is with oxygen and the other with a polypeptide chain.
There are two alpha and two beta subunits to this polypeptide chain in an adult and together these form globin. Globin cannot bind oxygen but can bind to CO2 and hydrogen ions.
The beta chains are able to bind to 2,3 diphosphoglycerate. The oxygenation of haemoglobin is a reversible reaction. The molecular shape of haemoglobin is such that binding of one oxygen molecule facilitates the binding of subsequent molecules.

The oxygen dissociation curve (ODC) describes the relationship between the percentage of saturated haemoglobin and partial pressure of oxygen in the blood.
Of note, it is not affected by haemoglobin concentration.

Chronic anaemia causes 2, 3 DPG levels to increase, hence shifting the curve to the right

Haldane effect – Causes the ODC to shift to the left. For a given oxygen tension there is increased saturation of Hb with oxygen i.e. Decreased oxygen delivery to tissues.
This can be caused by:
-HbF, methaemoglobin, carboxyhaemoglobin
-low [H+] (alkali)
-low pCO2
-ow 2,3-DPG
-ow temperature

Bohr effect – causes the ODC to shifts to the right = for given oxygen tension there is reduced saturation of Hb with oxygen i.e. Enhanced oxygen delivery to tissues. This can be caused by:
– raised [H+] (acidic)
– raised pCO2
-raised 2,3-DPG
-raised temperature

Ketamine, a phencyclidine derivative, is an antagonist at the NMDA receptor. It causes depression of the CNS that is dose dependent and induces a dissociative anaesthetic state with profound analgesia and amnesia.

Ketamine has a chiral centre usually presented as a racemic mixture with two optical isomers, S (+) and R (-) forms. These isomers are in equal proportions. The S (+) isomer is about three times more potent than the R (-) form. The S (+) form is less likely to cause emergence delirium and hallucinations.

Ketamine is extensively metabolised by hepatic microsomal cytochrome P450 enzymes producing norketamine as its main metabolite. Norketamine has a one third to one fifth as potency as its parent compound.
It increases the CMRO2, cerebral blood flow and potentially increase intracranial pressure.

Sugammadex is used for immediate reversal of rocuronium-induced neuromuscular blockade.
It is used at a dose of 16 mg/kg.

Since the patient in the question is 70 kg, the required dose of sugammadex can be calculated as:
16×70 = 1120 mg.

Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action. Due to its 1:1 binding of rocuronium or vecuronium, it can reverse any depth of neuromuscular block.