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.

Dopamine (DA) is a dopaminergic (D1 and D2) as well as adrenergic ? and?1 (but not ?2 ) agonist.

The D1 receptors in renal and mesenteric blood vessels are the most sensitive: i.v. infusion of a low dose of DA dilates these vessels (by raising intracellular cAMP). This increases g.f.r. In addition, DA exerts a natriuretic effect by D1 receptors on proximal tubular cells.

Moderately high doses produce a positive inotropic (direct?1 and D1 action + that due to NA release), but the little chronotropic effect on the heart.

Vasoconstriction (?1 action) occurs only when large doses are infused.

At doses normally employed, it raises cardiac output and systolic BP with little effect on diastolic BP. It has practically no effect on nonvascular ? and ? receptors; does not penetrate the blood-brain barrier—no CNS effects.

Dopamine is used in patients with cardiogenic or septic shock and severe CHF wherein it increases BP and urine outflow.

It is administered by i.v. infusion (0.2–1 mg/min) which is regulated by monitoring BP and rate of urine formation

The sternocleidomastoid muscle divides the neck into anterior and posterior triangles on both sides of the neck.

The posterior triangle has the following boundaries:
anteriorly – sternocleidomastoid muscle
posteriorly – trapezius
roof – investing layer of deep cervical fascia
floor – prevertebral fascia overlying splenius capitis, levator scapulae, and the scalene muscles

The contents of the posterior triangle are:
1. fat
2. lymph nodes (level V)
3. accessory nerve
4. cutaneous branches of the cervical plexus (A major branch of this plexus is the phrenic nerve, which arises from the anterior divisions of spinal nerves C3-C5)
5. inferior belly of omohyoid
6. branches of the thyrocervical trunk (transverse cervical and suprascapular arteries)
7. third part of the subclavian artery
8. external jugular vein

The volume expired in the first second of maximal expiration after a maximal inspiration is known as forced expiratory volume in one second (FEV1), and it indicates how quickly full lungs can be emptied. It is the most commonly measured parameter for bronchoconstriction assessment.

The maximum volume of air exhaled after a maximal inspiration is known as the ‘slow’ vital capacity (VC). VC is normally equal to FVC after a forced vital capacity (FVC) or slow vital capacity (VC) manoeuvre, unless there is an airflow obstruction, in which case VC is usually higher than FVC.

The FEV1/FVC (Tiffeneau index) is a clinically useful index of airflow restriction that can be used to distinguish between restrictive and obstructive respiratory disorders.

The average expired flow over the middle half (25-75 percent) of the FVC manoeuvre is the forced expiratory volume (FEF25-75). The airflow from the resistance bronchioles corresponds to this. It’s a more sensitive indicator of mild small airway narrowing than FEV1, but it’s difficult to tell if the VC (or FVC) is decreasing or increasing.

The maximum expiratory flow rate achieved is called the peak expiratory flow (PEF), which is usually 8-14 L/second.

An intercostal nerve block is used for therapeutic and diagnostic purposes. Intercostal nerve blocks manage acute and chronic pain in the chest area. Common indications are chest wall surgery and shingles or postherpetic neuralgia.

An intercostal nerve block is also an effective option for the management of pain associated with chest trauma and rib fractures. These blocks have been shown to improve oxygenation and respiratory mechanics, and offer pain relief that is comparable to that of epidural analgesia.

This technique, however, is limited by the relatively large doses of local anaesthetic required, and relatively high intravascular uptake from the intercostal space, increasing risk of local anaesthetic toxicity.

Opioid receptors are a large family of seven transmembrane domain receptors. They are of four types:

1) Delta opioid receptor

2) Mu opioid receptor

3) Kappa opioid receptor

4) Orphan receptor-like 1

They contain about 372-400 amino acids and thus their molecular weight is different.

Opioid receptor activation reduces the intracellular cAMP formation and opens K+ channels (mainly through µ and δ receptors) or suppresses voltage-gated N-type Ca2+ channels (mainly κ receptor). These actions result in neuronal hyperpolarization and reduced availability of intracellular Ca2+ which results in decreased neurotransmitter release by cerebral, spinal, and myenteric neurons (e.g. glutamate from primary nociceptive afferents).

However, other mechanisms and second messengers may also be involved, particularly in the long-term

Selegiline is a monoamine oxidase inhibitor. Inhibition of monoamine oxidase leads to increased levels of norepinephrine and serotonin in the central nervous system.

Pethidine, also known as meperidine, is a strong agonist at the mu and kappa receptors. It inhibits pain neurotransmission and blocks muscarinic-specific actions.

Administering opioid analgesic is relatively contraindicated to individuals taking monoamine oxidase inhibitors. This is because of the high incidence of serotonin syndrome, which is characterized by fever, agitation, tremor, clonus, hyperreflexia and diaphoresis. Onset of symptoms is within hours, and the treatment is mainly through sedation, paralysis, intubation and ventilation.

The clinical findings are more consistent with Serotonin syndrome rather than exacerbation of Parkinson’s. Parkinson’s Disease (PD) exacerbations are defined as patient-reported or caregiver-reported episodes of subacute worsening of PD motor function in 1 or more domains (bradykinesia, tremor, rigidity, or PD-related postural instability/gait disturbance) that caused a decline in functional status, developed over a period of < 2 months, did not fluctuate with medication timing, and are not caused by intentional adjustments of PD medications by the treating neurologist. Malignant hyperthermia usually occurs within minutes of administration of a volatile anaesthetic, such as halothane, or succinylcholine. There is massive release of calcium from the sarcoplasmic reticulum, leading to fever, acidosis, rhabdomyolysis, trismus, clonus, and hypertension. In sepsis, it more common for patients to present with hypotension rather than hypertension.

Monoamine oxidase (MOA) enzymes are responsible for the catalyses of monoamine oxidative deamination. It assists the degradation of serotonin, norepinephrine (NE) and dopamine.

They are found in the mitochondria of most central and peripheral nerve tissues.

There are 2 different types:

Type A: Whose main function it to inactivate dopamine, tyramine, norepinephrine and 5-hydroxytryptamine. In addition to the nervous system, it is also found in the liver, brain gastrointestinal tract, pulmonary endothelium and placenta
Type B: Whose main function is to inactivate dopamine, tyramine, tryptamine and phenylethylamine. In addition to the nervous system, it is also found in the liver, brain (especially in the basal ganglia) and blood platelets.

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

This question is asking which structure would lie posterior to the rectus abdominis muscle and not the prosthetic mesh, as only peritoneum lies posterior to mesh during a total extraperitoneal (TEP) hernia repair.

The region of the repair lies below the arcuate line, meaning that the transversalis fascia and peritoneum lie posterior to the rectus abdominis.

The bucks fascia lies within the penis.

Muscle fibre myosin ATPase histochemistry is used to divide the biochemical classification into two groups: type 1 and type II.

Type I (slow twitch) muscle fibres rely on aerobic glycolytic and aerobic oxidative metabolism to function. They have a lot of mitochondria, a good blood supply, a lot of myoglobin, and they don’t get tired easily.

Because they contain more motor units, Type II (fast twitch) muscle fibres are thicker. They are more easily fatigued, but produce powerful bursts. The capillary networks and mitochondria are less dense in these white muscle fibres than in type I fibres. They have a low myoglobin content as well.

Muscle fibres of type II (fast twitch) are divided into three types:

Type IIa – aerobic/oxidative metabolism is used.
Type IIb – anaerobic/glycolytic metabolism is used by these fibres.

When compared to skeletal muscle, cardiac and smooth muscle twitch at a slower rate.

The intrinsic pathway is best assessed by the aPTT time.

D-dimer is a fibrin degradation product which is raised in the presence of blood clots.

A 50:50 mixing study is used to assess if a prolonged PT or aPTT is due to factor deficiency or a factor inhibitor.

The thrombin time is a test used to assess fibrin formation from fibrinogen in plasma. Factors that prolong the thrombin time include heparin, fibrin degradation products, and fibrinogen deficiency.

Intrinsic pathway – Best assessed by APTT. Factors 8,9,11,12 are involved. Prolonged aPTT can be seen in haemophilia and use of heparin.

Extrinsic pathway – Best assessed by Increased PT. Factor 7 involved.

Common pathway – Best assessed by APTT & PT. Factors 2,5,10 involved.

Vitamin K dependent factors are factors 2,7,9,10

The internal jugular vein is found on both sides of the neck and collects blood from the brain, superficial regions of the face, and neck. It drains into the right atrium.

It is a continuation of the sigmoid sinus and begins in the posterior cranial fossa and exits the skull via the jugular foramen.
It runs within the carotid sheath as it descends in the neck and is accompanied by the vagus nerve posteriorly and the common carotid anteromedially.

The hypoglossal nerve emerges from the hypoglossal canal medial to the internal carotid artery and the internal jugular vein and ninth, tenth, and eleventh cranial nerves.

The internal jugular vein crosses anterior to the thoracic duct on the left side.

A mercury barometer can be used to determine absolute pressure. A glass tube with one closed end serves as the barometer. The open end is inserted into a mercury-filled open vessel. The mercury in the container is pushed into the tube by atmospheric pressure exerted on its surface. Absolute pressure is the distance between the tube’s meniscus and the mercury surface.

Pressure is defined as force in newtons per unit area (F) (A). 

Mass of mercury = area (A) × density (ρ) × length (L)
Pressure = ((A × ρ × L) × 9.8 m/s2)/A
Pressure = ρ × L x 9.8
Pressure is proportional to L

The numerator and denominator of the above equation, area (A), cancel out. The constants are density and the gravitational acceleration value.

The length is proportional to the applied pressure.

Krebs’ cycle (tricarboxylic acid cycle or citric acid cycle) is a sequence of reactions in which acetyl coenzyme A (acetyl-CoA) is metabolised and this results in carbon dioxide and hydrogen atoms production.

This series of reactions occur in the mitochondria of eukaryotic cells, not the cytoplasm. The cycle requires oxygen and so, cannot function under anaerobic conditions.

It is the common pathway for carbohydrate, fat and some amino acids oxidation and is required for high energy phosphate bond formation in adenosine triphosphate (ATP).

When pyruvate enters the mitochondria, it is converted into acetyl-CoA. This represents the formation of a 2 carbon molecule from a 3 carbon molecule. There is loss of one CO2 but formation of one NADH molecule. Acetyl-CoA is condensed with oxaloacetate, the anion of a 4 carbon acid, to form citrate which is a 6 carbon molecule.

Citrate is then converted into isocitrate, alpha-ketoglutarate, succinyl-CoA, succinate, fumarate, malate and finally oxaloacetate.

The only 5 carbon molecule in the cycle is alpha-ketoglutarate.

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.

Amyl nitrate is part of the treatment of cyanide poisoning. The short acting nitrate causes oxidation of Fe2+ in haemoglobin to Fe3+ in methaemoglobin. Methaemoglobin combines with cyanide (cyanmethemoglobin), which reacts with sodium thiosulfate to convert nontoxic thiocyanate and methaemoglobin.

Methaemoglobin is formed when the iron in haemoglobin is converted from the reduced state (Fe2+) to the oxidized state (Fe3+). The oxidized form of haemoglobin (Fe3+) does not bind oxygen as readily as Fe2+, but has high affinity for cyanide. It also results to high affinity of bound oxygen to haemoglobin, thus leading to tissue hypoxia. Arterial oxygen tension is normal despite observations of cyanosis and dyspnoea. Methemoglobinemia can be treated with methylene blue and vitamin C.

Carboxyhaemoglobin can be due to carbon monoxide poisoning. In such cases, patients experience headache and dizziness, but do not develop cyanosis.

2,3-diphosphoglycerate causes a shift in the oxygen dissociation curve to the right, decreasing haemoglobin’s affinity to oxygen to facilitate unloading of oxygen to the tissues.

Cardiac conduction

Phase 0 – Rapid depolarization. Opening of fast sodium channels with large influx of sodium

Phase 1 – Rapid partial depolarization. Opening of potassium channels and efflux of potassium ions. Sodium channels close and influx of sodium ions stop

Phase 2 – Plateau phase with large influx of calcium ions. Offsets action of potassium channels. The absolute refractory period

Phase 3 – Repolarization due to potassium efflux after calcium channels close. Relative refractory period

Phase 4 – Repolarization continues as sodium/potassium pump restores the ionic gradient by pumping out 3 sodium ions in exchange for 2 potassium ions coming into the cell. Relative refractory period

In the Child-Pugh classification system, the following 5 components are determined or calculated in order:

Ascites

Grade of encephalopathy

Serum bilirubin (?mol/L)

Serum Albumin (g/L)

Prothrombin time or INR

Raised liver enzymes are not the component of the classification system.

The central venous pressure (CVP) waveform depicts changes of pressure within the right atrium. Different parts of the waveform are:

A wave: which represents atrial contraction. It is synonymous with the P wave seen during an ECG. It is often eliminated in the presence of atrial fibrillation, and increased tricuspid stenosis, pulmonary stenosis and pulmonary hypertension.

C wave: which represents right ventricle contraction at the point where the tricuspid valve bulges into the right atrium. It is synonymous with the QRS complex seen on ECG.

X descent: which represents relaxation of the atrial diastole and a decrease in atrial pressure, due to the downward movement of the right ventricle as it contracts. It is synonymous with the point before the T wave on ECG.

V wave: which represents an increase in atrial pressure just before the opening of the tricuspid valve. It is synonymous with the point after the T wave on ECG. It is increased in the background of a tricuspid regurgitation.

Y descent: which represents the emptying of the atrium as the tricuspid valve opens to allow for blood flow into the ventricle in early diastole.

Canon waves: which refer to large waves present on the trace that do not correspond to the A, V or C waves. They usually occur in a background of complete heart blocks or junctional arrythmias.

Selection of a chest drain will depend on the external circumference.

A cannula, whether intravenous or intra-arterial, are classified according to standard wire gauge, which refers to the number of wires that can fit into the same hole. If a cannula is labelled 22G, then 22 wires will fit into the standard size hole.

A more popular measurement than SWG nowadays is cross sectional area.

When the concern for selecting equipment is the rate of flow, then it is important to consider the diameter and the radius of a parallel sided tube. These, however, are not routinely considered when comparing sizes of a cannula.

If the afterload and myocardiac contractility remains unchanged, an increase in the preload can be attributed to an increase in end-diastolic volume.

Preload can be defined as the initial stretching of the cardiac myocytes prior to contraction. Preload, therefore, is related to muscle sarcomere length. Because sarcomere length cannot be determined in the intact heart, other indices of preload are used such as ventricular end-diastolic volume or pressure. When venous return to the heart is increased, the end-diastolic pressure and volume of the ventricles are increased, which stretches the sarcomeres, thereby increasing their preload.

Noradrenaline also called norepinephrine belongs to the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter.

They have sympathomimetic effects acting via adrenoceptors (?1, ?2,?1, ?2, ?3) or dopamine receptors (D1, D2).

May cause reflex bradycardia, reduce cardiac output and increase myocardial oxygen consumption

The larynx is an air passage, sphincter, and organ of phonation that extends from the tongue to the trachea. It lies in the anterior part of the neck at the vertebral levels C3 to C6.

Important anatomical landmarks:
C1-C2 – Atlas and axis, respectively

C3-C6 – Larynx

C5 – Thyroid cartilage

T5-T7 – Pulmonary hilum

T12-L1 – Duodenum

The formula for calculating air: oxygen entrainment ratio is given as :
100% − FiO2 = air/oxygen entrainment ratio
Since FiO2 − 21% and the entrainment ratio is already known. Substituting the values in the equation: x = FiO2.

100 − x = 9
x − 21
100 − x = 9(x − 21)
100 − x = 9x − 189
10x = 289
x = 289/10
x = 28.9%

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.

Phase IIa studies are usually pilot studies designed to demonstrate clinical efficacy or biological activity (‘proof of concept’ studies) whereas phase IIb studies determine the optimal dose at which the drug shows biological activity with minimal side-effects (definite dose-finding studies).

Phase III and Phase IV studies are performed on larger set of participants (usually hundreds to thousands) when safety and efficacy have been established.

The cephalic vein is a superficial vein that runs through the forearm and the arm, before draining into the axillary vein where it terminates.

Tracheal tubes are made of either disposable plastic or reusable red rubber.

The tube size refers to the internal diameter (ID) in mm which is marked on the outside of the tube (some manufacturers mark the external diameter on the outside).

Plastic tubes have a radiopaque line spanning the entire length of the tube, which allows their position to be identified on x-rays. The bevel located at the end of the tube is left-facing and oval in shape, which improves the view of the vocal cords during intubation.

Oxford tubes are L-shaped and have a bevel that faces posteriorly. They have thick walls that increase the external diameter, making for a wider internal diameter.

RAE (Ring, Adair, and Elwyn) tubes are preformed and can either be north or south facing and cuffed or uncuffed. The cuffed RAE tubes have one Murphy eye, whereas the uncuffed has two Murphy eyes. Uncuffed tubes are primarily used in paediatric anaesthesia and the two Murphy eyes ensure adequate ventilation- should the tube be too long.

Ampicillin belongs to the family of penicillin. Resistance to this group of drugs is due to ?-lactamase production which opens the ?-lactam ring and inactivates Penicillin G and some closely related congeners. The majority of Staphylococci and some strains of gonococci, B. subtilis, E. coli, and a few other bacteria produce penicillinase.

Resistance to cephalosporins is due to changes in penicillin-binding proteins.

Resistance to macrolides are due to post-transcriptional methylation of 23s bacterial ribosomal RNA

Resistance to fluoroquinolones is due to mutations in DNA gyrase.

The Weibull distribution are used to describe various types of observed failures of the components. it is used in reliability and survival analysis.

Regression Analysis is used to measure the relationship between among two or more variable. It determines the effect of independent variables on the dependent variables.

Student t-test is one of the most commonly used method to test the hypothesis. It determines the significant difference between the means of two different groups.

A time series is a collection of observations of well-defined data obtained at regular interval of time.

Kaplan-Meier estimator is used to estimate the survival function from lifetime data. It can be derived from maximum likelihood estimation of hazard function. It is most likely used to measure the fraction of patient’s life for a certain amount of time after treatment.

The posterior pituitary is made up mostly of neural tissue. It is responsible for the storage and release of 2 hormones:
– antidiuretic hormone (ADH)
– oxytocin.

These two hormones are synthesised in the supraoptic and paraventricular nuclei of the hypothalamus.

After ingestion of more than 150 mg/kg paracetamol within 24 hours, hepatotoxicity can occur but can also develop rarely after ingestion of doses as low as 75 mg/kg within 24 hours. Hepatocellular damage will not occur in this patient and therefore no need to engage management pathway for paracetamol overdose. If his weight was <33 kg or he already had a history of impaired liver function, then the management would bde different. Subsequent post-operative doses will be a standard dose of 1 g 6 hourly. This is a drug administration error and should be reported as an incident even though the patient will not be harmed.

Based on the presenting symptoms, this is the case of bacterial meningitis. The treatment of choice for bacterial meningitis is a cephalosporin. Cephalosporin acts by inhibiting bacterial cell wall synthesis.

The inguinal canal is the pathway leading from the wall of the abdomen to the external genitalia.

The borders of the inguinal canal are:

Anterior wall: formed by the aponeurosis of the external oblique, supported by the internal oblique muscle laterally.

Posterior wall: formed laterally by the transversalis fascia, and medially by the conjoint tendon

Roof: formed by the internal oblique and transversus abdominis muscles

Floor: formed by the inguinal ligament and supported medially by the lacunar ligament

The upper five cervical segments of the spinal cord give rise to the XI cranial nerve. They connect with a few smaller branches before exiting the skull through the jugular foramen. The sternomastoid and trapezius muscles get their motor supply from the accessory root. Except for the palatoglossus, the hypoglossal nerve supplies motor supply to all tongue muscles.

The inability to shrug the shoulder on the affected side and rotate the head to the side against resistance is caused by damage to the spinal accessory nerve. This is due to the trapezius and sternomastoid muscles’ weakness.

The hypoglossal nerve is damaged, resulting in tongue wasting and inability to move from side to side.

The stylopharyngeus receives motor supply from the glossopharyngeal nerve. It also carries taste sensory fibres from the back third of the tongue, as well as the carotid sinus, carotid body, pharynx, and middle ear.

Motor supply to the larynx, pharynx, and palate; parasympathetic innervation to the heart, lung, and gut; and sensory fibres from the epiglottis and valleculae are all provided by the vagus nerve.

Exposure to anaesthetic hazards is one among the occupational exposures in manipulating toxic agents or inhaling toxic gases during anaesthetic practices.

Toxic gases mainly nitrous oxide, is one of the most gaseous anaesthetic agents that constitutes an important source of pollution. One of the safe and effective technics used in anaesthesia and reducing the amount of pollution is the Total Intravenous Anaesthesia (TIVA) which consists of using opioids in analgesia and propofol for the induction and the maintenance of anaesthesia. It refers to the administration intravenously of an anaesthetic, sedative, and/or tranquilizer. A less polluting but not the best way to get rid of the toxic aesthetic agents is the scavenger system that collects and expels the gas outside the medical environment. Yet, this technique still represents a hazard for the environment and still increase the risk of exposure for the health workers and clinical staff.

Fume cupboards are also not recommended to use because of their high pollution potency, mainly of the air resulting in a great harm for medical workers.

Supraglottic airways as well as the Air Changes per Hour technics could be harmful for both patients and health workers, increasing the risks of transmitted diseases, namely nosocomial infections.

Therefore, the Total Intravenous Anaesthesia technique (TIVA) is most likely to be safe and recommended to use.

Randomisation allows for performance of experimental trials in a random order. Using this method gives us control over the confounding variables that are not supposed to be held constant.

For an instance, by employing randomisation we get to control biological differences among individual human beings during experimental trials.

Barbituric acid is the barbiturates’ pharmacologically inactive precursor. A pyrimidine heterocyclic nucleus is formed by the condensation of urea and malonic acid. Its pharmacological activity can be influenced by minor structural changes (structure function relationship).

The duration of action and potency as a sedative are influenced by the length of the side chains at C5. Barbiturates with three carbon atoms in their chain last longer than those with two. Anticonvulsant properties are enhanced by branched chains.

The addition of a methyl group at N1 causes a faster onset/offset of action, but it also causes excitatory phenomena (twitching/lower convulsive threshold).

The addition of oxygen and sulphur to C2 increases the molecule’s lipid solubility and thus its potency. Thiopentone (thiobarbiturate) has sulphur groups at C2, making it 20-200 times more lipid soluble than oxybarbiturates.

A single chamber pacemaker was implanted in the patient. In VVI mode, a pacemaker paces and senses the ventricle while being inhibited by a perceived ventricular event. The most likely electrical hazard from diathermy is electromagnetic interference (EMI).

EMI has the potential to cause the following: Inhibition of pacing
Asynchronous pacing
Reset to backup mode
Myocardial burns, and
Trigger VF.

Diathermy entails the implementation of high-frequency electrical currents to produce heat and either make incisions or induce coagulation. Monopolar cautery involves disposable cautery pencils and electrosurgical diathermy units. In typical monopolar cautery, an electrical plate is placed on the patient’s skin and acts as an electrode, while the current passes between the instrument and the plate. Monopolar diathermy can therefore interfere with implanted metal devices and pacemaker function.

Bipolar diathermy, where the current passes between the forceps tips and not through the patient and is less likely to generate EMI.

Whilst the presence of a CVP line may in theory predispose the patient to microshock, the use of prerequisite CF electrical equipment makes this very unlikely. The presence of a CVP line and pacemaker does not therefore unduly increase the risk of an electrical hazard.

Isolating transformers are used to protect secondary circuits and individuals from electrical shocks. There is no step-up or step-down voltage (i.e. there is a ratio of 1 to 1 between the primary and secondary windings).

A ground (or earth) wire is normally connected to the metal case of an operating table to protect patients from accidental electrocution. In the event that a fault allows a live wire to make contact with the metal table (broken cable, loose connection etc.) it becomes live. The earth will provide an immediate path for current to safely flow through and so the table remains safe to touch. Being a low resistance path, the earth lets a large current flow through it when the fault occurs ensuring that the fuse or RCD will quickly blow. Without an operating table earth, the patient is not at more risk of an electrical hazard because of the pacemaker.

A damped sine wave is a smooth, periodic oscillation with an amplitude that approaches zero as time goes to infinity. In other words, the wave gets flatter as the x-values become larger.

Critical damping is defined as the threshold between overdamping and underdamping. In the case of critical damping, the oscillator returns to the equilibrium position as quickly as possible, without oscillating, and passes it once at most.

In overdamping, the system moves slowly towards the equilibrium. An underdamped system moves quickly to equilibrium, but will oscillate about the equilibrium point as it does so.

Optimal damping has a damping coefficient of around 0.64-0.7. It maximizes frequency response, minimizes overshoot of oscillations, and minimizes phase and amplitude distortion.

In an undamped system, the amplitude of the waves that are being generated remain unchanged and constant over time.

The amount of oxygen carried by 100 ml of blood is called the arterial oxygen content (CaO2)and is normally 17-24 ml/dL and can be determined by this equation:

CaO2 = oxygen bound to haemoglobin + oxygen dissolved in plasma

CaO2 = (1.34 × Hgb × SaO2 × 0.01) + (0.003 × PaO2)

where:

1.34 = Huffner’s constant (D) – Huffner’s constant does not change and its magnitude relatively small.
Hgb is the haemoglobin level in g/dL and SaO2 is the percent oxyhaemoglobin saturation of arterial blood
PaO2 is (0.0225 = ml of O2 dissolved per 100 ml plasma per kPa, or 0.003 ml per mmHg).

Quantitatively, the amount of oxygen dissolved in plasma is 0.3 mL/dL.

Henry’s law states that at constant temperature, the amount of gas dissolved at equilibrium in a given quantity of a liquid is proportional to the pressure of the gas in contact with the liquid.

Given a haemoglobin concentration of 15 g/dL and a SaO2 of 100% and a PaO2 of 13.3 kPa, the amount of oxygen bound to haemoglobin is 20.4 mL/100mL.

Cardiac output is an important determinant of oxygen delivery but does not influence the oxygen content of blood.

The membranous urethra is the shortest part of the urethra and the least dilatable part of it.

This is as a result of it being surrounded by the external urethral sphincter which is made up of striated muscle and controls voluntary urine flow from the bladder to the urethra.

A forest plot is a graphical representation that summarizes the findings of several research, such as a meta-analysis of a series of randomized controlled trials.

The Kaplan-Meier estimate shows survival over time, for example, plotting the number of patients still alive seven years after chemotherapy for lung cancer.

Fisher’s exact test similarly uses contingency tables to assess statistical significance, however, it is typically used when sample sizes are small.

Chi-square test assesses whether an association exists between two categorical variables using the observed and expected frequencies. For instance, is social class (I-V) related to body mass index (BMI) category? Using the observed and anticipated frequencies, the Chi-square test determines whether a connection exists between two categorical variables. For example, is socio-economic status related to BMI category?

Linear regression is a technique which attempts to model the relationship between two variables by fitting a linear equation to observed data. Linear regression uses correlation between two continuous variables. As correlation only indicates the strength of an association only, it cannot be used to forecast the change in one variable when a second variable is altered.

This equation takes the form y = mx + c, where ‘y’ is the dependent variable, ‘x’ is the independent variable, ‘m’ is the slope of the line and ‘c’ is the intercept. In this example, for a range of heights, it would be possible to map a line of best fit to a scatter plot and thus predict the forced expiratory volume (FEV1) for an individual.

Number needed to treat can be defined as the number of patients who need to be treated to prevent one additional bad outcome.

It can be found as:

NNT=1/Absolute Risk Reduction (rounded to the next integer since number of patients can be integer only).

where ARR= (Risk factor associated with the new drug group) — (Risk factor associated with the currently available drug)

So,

ARR= (0.04-0.03)

ARR= 0.01

NNT= 1/0.01

NNT=100

The drug of choice for the treatment of anaphylaxis is adrenaline. It has an intravenous route of administration. Since the patient already has intravenous access, the intramuscular route is not appropriate.

Second-line pharmacological intervention includes the use of chlorpheniramine 10mg intravenous, Hydrocortisone 200mg.

Triiodothyronine (T3) is more potent than thyroxine (T4). It is able to bind to more receptors (90%) compared to T4 (10%), and the onset of action is more immediate (within 12 hours) than T4 (2 days).

Ninety-three percent of thyroid hormones synthesized is T4, and the remaining 7% is T3. The half-life of T3 is shorter (1 day), and its affinity for thyroxine-binding globulin is lower than T4.

The equation for calculating vaporiser output is:

Vaporiser output (VO) mL = Carrier gas flow (mL/minute) × SVP of agent (kPa)
Ambient pressure (kPa) − SVP of agent (kPa)

The saturated vapour pressure of sevoflurane at 1 atm (100 kPa) and 20°C is 21 kPa.

VO = (100 mL × 21 kPa)/(100 kPa − 21kPa) for sevoflurane,
VO = 26.6 mL

26.6 mL of 100% sevoflurane and 100 mL bypass carrier gas is being added to the fresh gas flow per minute.

2660 mL of 1% sevoflurane and 100 mL bypass carrier gas is approximately 2.7 L/minute.

The following units are derived SI units of measurement.

Energy or work: kg.m2.s-2
The Joule (J) is the energy transferred to an object when a force of one newton acts on that object in the direction of its motion through a distance of one meter or N.m.

Power: kg.m2.s-3
The Watt (W) = rate of transfer of energy or Joule per second J/s.

Force: kg.m.s-2
One Newton (N) which is the international unit of measure for force = 1 kilogram meter per second squared. 1 Newton of force is the force required to accelerate an object with a mass of 1 kilogram 1 meter per second per second.

Volt: kg.m2.s-3.A-1
The volt (V) is defined as the potential difference across a conductor when a current of one ampere dissipates one watt of power or W/A.

Pressure: kg.m-1.s-2
A pascal (Pa) is force per unit area or N/m2.

There is minimum mixing of blood passing through the vessels.

The cerebral hemispheres are supplied by arteries that make up the Circle of Willis. The Circle of Willis is formed by the anastomosis of the two internal carotid arteries and two vertebral arteries. It lies in the subarachnoid space within the basal cisterns that surround the optic chiasma and infundibulum.

Each half of the circle is formed by:
1. Anterior communicating artery
2. Anterior cerebral artery
3. Internal carotid artery
4. Posterior communicating artery
5. Posterior cerebral arteries and the termination of the basilar artery

The circle and its branches supply; the corpus striatum, internal capsule, diencephalon, and midbrain

Structural isomers have a similar molecular formula, but they have a different structural formula as their atoms are arranged in a different manner. Such small changes lead to the differential pharmacological activity. Enflurane and isoflurane are two prime examples of structural isomers.

Stereoisomers are those substances that have a similar molecular and structural formula, but the arrangement spatially of atoms are different and have optical activity.

Enantiomers are a pair of stereoisomers, which are non-superimposable mirror images of each other. They also have chiral centres of molecular symmetry. Ketamine is considered as an example of racemic mixture (contain 50% R and 50% S enantiomers)

Geometric isomers contain a carbon-carbon double bond (i.e. C=C) or a rigid carbon-carbon single bond in a heterocyclic ring. Cis-atracurium is one example.

Dynamic isomers or Tautomers are a pait of unstable structural isomers, which are present in equilibrium. One isomer can easily change after the change in pH. Midazolam and thiopentone are their examples.

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

There are 4 different types of globin chains which surround 4 heme molecules in haemoglobin (Hb) – α (alpha), β (beta), γ (gamma), and δ (delta)
α chains are essential.
δ2β2 and β2γ2 are not found in a healthy adult.
97% of the Hb in a healthy adult is made of α2β2 (2 α chains and 2 β chains).
α2δ2 accounts for around 1.5-3% of the adult Hb.
α2γ2 accounts for less than 1%.

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 respiratory quotient (RQ) is the ratio of CO2 produced by the body to O2 consumed in a given amount of time.

CO2 produced / O2 consumed = RQ

CO2 is produced at a rate of 200 mL per minute, while O2 is consumed at a rate of 250 mL per minute. An RQ of around 0.8 is typical for a mixed diet.

The RQ will change depending on the energy substrates consumed in the diet. Granulated sugar is a refined carbohydrate that contains 99.999 percent carbohydrate and no lipids, proteins, minerals, or vitamins.

Glucose and other hexose sugars (glucose and other hexose sugars):
RQ=1

Fats:
RQ = 0.7

Proteins:
Approximately 0.9 RQ

Ethyl alcohol is a type of alcohol.

200/300 = 0.67 RQ

For complete oxidation, lipids and alcohol require more oxygen than carbohydrates.

When carbohydrate is converted to fat, the RQ can rise above 1.0. Fat deposition and weight gain are likely to occur in these circumstances.

Based on the laboratory reports, the patient is suffering from significant hyponatremia. The symptoms of hyponatremia are mainly neurological and depend on the severity and rapidity of onset of hyponatremia.

Patient symptom according to the hyponatremia level is correlated below:

125 – 130mmol/L – Nausea and malaise
115 – 125mmol/L – Headache, lethargy, seizures, and coma
<120mmol/L - Up to 11% present with coma.

99.7% of the values within 3 standard deviations of the mean.

For 99.7% confidence interval, you can find the range as follows:

1. Multiply the standard error by 3.

2. Subtract the answer from mean value to get the lower limit.

3. Add the answer obtained in step 1 from the mean value to get the upper limit.

For a confidence interval of 68%, multiply the standard error with 1 and repeat the process. For a 95% confidence interval, Standard Error is multiplied by 1.96 to get the interval.

Gabapentin is an amino acid-like molecules that was originally synthesized as an analogue of GABA but is now known not to act through GABA mechanisms. It is used in the treatment of focal seizures and various nonepilepsy indications, such as neuropathic pain, restless legs syndrome, and anxiety disorders.

Despite its close structural resemblance to GABA, gabapentin does not act through effects on GABA receptors or any other mechanism related to GABA-mediated neurotransmission. Rather gabapentin binds avidly to ?2?, a protein that serves as an auxiliary subunit of voltage-gated calcium channels. Moreover, it binds to NMDA receptor to modulate its transmission.

Standard error can be calculated by the following formula:

Standard Error= (Standard Deviation)/√(Sample Size)
= (12) / √(64)
= 12 / 8
= 1.5

Peak expiratory flow rate (PEFR) is the maximum speed of air flow generated during a single forced exhaled breath. It is most useful when expressed as a percentage of the best value obtained from the patient.

Forced expiratory volume over 1 second (FEV1) is a lung parameter measured using spirometry. It is the amount of air forced out of the lung in one exhaled breath. It is a more accurate measure of lung obstructions as it doesn’t rely on effort like PEFR

PEFR and FEV1 are usually similar, but become more different in asthmatic patients as airflow becomes increasingly obstructed.

Acute severe asthma is most often diagnosed on history taking and examinations:

Respiratory rate: >25 breaths/min
Heart rate: >110 beats/min
PEFR: 33 – 50% predicted (<200L/min)
Patient state: Unable to complete a sentence in a single breath.

A chest x-ray is not routinely required, and is only indicated in specific circumstances, which are:

If a pneumomediastinum or pneumothorax is suspected
Possible life threatening asthma
Possible consolidation
Unresponsive asthma
If ventilation is required.

An echocardiograph (ECG) is not necessary in this case

Routine haematological and biochemical investigations are not urgent in this case as any abnormalities they detect will be secondary to the patient’s presentation.

An arterial blood gas (ABG) will only be indicated if SPO2 was <92% or if patient presented with life threatening symptoms.

During analytical stage a technique called stratification is used for controlling confounding variables. This technique involves sorting out the data into discernible groups.

A nominal volume of 2 litres is contained in a CD cylinder. It has a pressure of 230 bar when full and contains litres 460 L of useable oxygen at STP.

For every 1000 mL 100% oxygen there will be an entrainment of 1000 mL or air (20% oxygen) in an air/oxygen mix.

The average concentration is, therefore, 120/2=60% or 0.6.

Detsky’s Modified cardiac risk classification system in patients undergoing non-cardiac surgery:

Age more than 70: 05 points

History of myocardial infarction:

Less than 6 months: 10 points
More than 6 months: 5 points

Angina Pectoris:

Angina with minimal exertion: 10 points

Angina at any level of exertion: 20 points

Pulmonary Oedema:

Within 7 days: 10 points
At any time: 5 points

Suspected aortic valve stenosis with valve area <0.6cm2: 20 points Arrhythmia: Any rhythm other than sinus or sinus with premature atrial complexes (PACs): 5 points More than 5 premature ventricular contractions: 5 points
Emergency Surgery: 10 points
Deficient general medical condition: 5 points

Risk classification:

Grade I: 0-15 points = low risk
Grade II: 15-30 points = moderate risk
Grade III: >30 points = high risk

Noradrenaline has a short half-life of about 2 minutes. It is rapidly cleared from plasma by a combination of cellular reuptake and metabolism.

It acts as sympathomimetics by acting on ?1 receptors and also on ? receptors.

It decreases renal and hepatic blood flow.

Norepinephrine is metabolized by the enzymes monoamine oxidase and catechol-O-methyltransferase to 3-methoxy-4-hydroxymandelic acid and 3-methoxy-4-hydroxyphenylglycol (MHPG).

Natural catecholamines are Adrenaline, Noradrenaline, and Dopamine

The coeliac axis refers to one of the splanchnic arteries located within the abdomen.

It arises from the aorta almost horizontally at the level of the T12 vertebrae

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.

The following is the alveolar gas equation:

PAO2 = PiO2 − PaCO2/R

Where:

PAO2 is the partial pressure of oxygen in the alveoli.
PiO2 is the partial pressure of oxygen inhaled.
PaCO2 stands for partial pressure of carbon dioxide in the arteries.
The amount of carbon dioxide produced (200 mL/minute) divided by the amount of oxygen consumed (250 mL/minute) equals R = respiratory quotient. With a normal diet, the value is 0.8.

By subtracting the partial pressure exerted by water vapour at body temperature, the PiO2 can be calculated:

PiO2 = 0.21 × (100 kPa − 6.3 kPa)
PiO2 = 19.8

Substituting:
PAO2 = 19.8 − 10/0.8
PAO2 = 19.8 − 12.5
PAO2 = 7.3k Pa

Perioperative and postoperative analgesia can both be provided by an inguinal hernia field block. The Iliohypogastric and ilioinguinal nerves, as well as the skin, superficial fascia, and deeper structures, must be blocked for maximum effectiveness. The local anaesthetic should ideally have a long duration of action, be highly concentrated, and have a volume of at least 30 mL.

Plain bupivacaine has a maximum safe dose of 2 mg/kg body weight.

Because the patient weighs 75 kg, 150 mg bupivacaine can be safely administered. Both 30 mL 0.5 percent bupivacaine (150 mg) and 60 mL 0.25 percent bupivacaine (150 mg) are acceptable doses, but 30 mL 0.5 percent bupivacaine represents the optimal volume and strength, potentially providing a denser and longer block.

The maximum safe dose of plain lidocaine has been estimated to be between 3.5 and 5 mg/kg. The patient weighs 75 kg and can receive a maximum of 375 mg using the higher dosage regimen:

There are 200 mg of lidocaine in 10 mL of 2% lidocaine (and therefore 11 mL contains 220 mg)
200 mg of lidocaine is contained in 20 mL of 1% lidocaine.

While alternatives are available, Although the doses of 11 mL lidocaine 2% and 20 mL lidocaine 1% are well within the dose limit, the volumes used are insufficient for effective field block for this surgery.

With 1 in 200,000 epinephrine, the maximum safe dose of lidocaine is 7 mg/kg. The patient can be given 525 mg in this case. Even with epinephrine, 60 mL of 1% lidocaine is 600 mg, which could be considered an overdose.

The renal effects of atrial natriuretic peptide (ANP) secretion are as follows:

Increased glomerular filtration rate by dilating the afferent glomerular arteriole. Moreover, it constricts the efferent glomerular arteriole, and relaxes the mesangial cells.
Reduces sodium reabsorption in the collecting ducts and distal convoluted tubule.
The renin-angiotensin system (RAS) is inhibited.
Blood flow in the vasa recta is increased.

Because plasma osmolality is unlikely to change, hypothalamic osmoreceptors are unaffected.

The plasma protein has a molecular weight of 66 kDa, is not normally filtered into the proximal convoluted tubule, and has no osmotic diuretic effect.

The following are some basic assumptions:

Extracellular fluid (ECF) makes up one-third of total body water (TBW), while intracellular fluid makes up the other two-thirds (ICF)
One-quarter plasma and three-quarters interstitial fluid make up ECF (ISF)
The volume receptors in the atria have a 7-10% blood volume change threshold.
The osmoreceptors are sensitive to changes in osmolality of 1-2 percent.
The normal plasma osmolality before the transfusion is 287-290 mOsm/kg.
The plasma protein solution is a colloid that is only delivered to the intravascular compartment. The tonicity remains unchanged.
The blood volume increases by 20%, from 5,000 mls to 6,000 mls. This is higher than the volume receptor threshold of 7 to 10%.

Two mechanisms are responsible for autoregulation of RBF and GFR: one mechanism that responds to changes in arterial pressure and another that responds to changes in [NaCl] in tubular fluid. Both regulate the tone of the afferent arteriole. The pressure-sensitive mechanism, the so-called myogenic mechanism, is related to an intrinsic property of vascular smooth muscle: the tendency to contract when stretched. Accordingly, when arterial pressure rises and the renal afferent arteriole is stretched, the smooth muscle contracts in response. Because the increase in resistance of the arteriole offsets the increase in pressure, RBF, and therefore GFR, remains constant.

The second mechanism responsible for autoregulation of GFR and RBF is the [NaCl]-dependent mechanism known as tubuloglomerular feedback. This mechanism involves a feedback loop in which a change in GFR leads to alteration in the concentration of NaCl in tubular fluid, which is sensed by the macula densa of the juxtaglomerular apparatus and converted into signals that affect afferent arteriolar resistance and thus the GFR (Fig. 33.19). For example, when the GFR increases and causes [NaCl] in tubular fluid in the loop of Henle to rise, more NaCl enters the macula densa cells in this segment (Fig. 33.20). This leads to an increase in formation and release of adenosine triphosphate (ATP) and adenosine (a metabolite of ATP) by macula densa cells, which causes vasoconstriction of the afferent arteriole and normalization of GFR. In contrast, when GFR and [NaCl] in tubule fluid decrease, less NaCl enters the macula densa cells, and both ATP and adenosine production and release decline. The fall in [ATP] and [adenosine] results in afferent arteriolar vasodilation, which returns GFR to normal. NO, a vasodilator produced by the macula densa, attenuates tubuloglomerular feedback, whereas angiotensin II enhances tubuloglomerular feedback. Thus the macula densa may release both vasoconstrictors (e.g., ATP and adenosine) and a vasodilator (e.g., NO) that oppose each other’s action at the level of the afferent arteriole. Production plus release of either vasoconstrictors or vasodilators ensures exquisite control over tubuloglomerular feedback.

Renal autoregulation, thus, reduces the effect of changes in arterial blood pressure on renal sodium excretion.

When using dry soda lime for VOCs, very high amounts of carbon monoxide may be produced, regardless of the inhalational anaesthetic agent used. The carbon monoxide produced is sufficient enough to cause cytotoxic and anaemic hypoxia. To prevent this, soda lime canisters are shaken well to even out the packing of granules. This can help to evenly distribute gas flow for proper CO2 absorption and ventilation.

Compound A is formed when dry soda lime, or soda lime in high temperature, reacts with the inhalational anaesthetic Sevoflurane. Animal studies have shown renal toxicity in rats, but renal adverse effects in humans are yet to be observed.

When monitors are not employed with VOCs, deleterious effects are not for certain. However, monitors not employed with vaporiser inside the circuit (VIC) can lead to significant adverse events.

The basilar artery is a large vessel that is formed by the union of the vertebral arteries at the junction of the medulla and pons. It lies in the pontine cistern and follows a shallow groove on the ventral pontine surface, extending to the upper border of the pons.

The basilar artery then bifurcates into the two posterior cerebral arteries that form part of the Circle of Willis.

Opioid should be avoided in the caesarean section as it crosses the placental membrane and causes respiratory depression.

Even though inhalational and intravenous anaesthetic agents readily cross the placenta, they do not have significant effects on APGAR score when used in clinical doses.

Vecuronium and suxamethonium are highly polar molecules and thus do not cross the placenta in significant amounts.

Lorazepam is an intermediate-acting benzodiazepine that binds to the GABA-A receptor subunit to increase the frequency of chloride channel opening and facilitate membrane hyperpolarization. It is the preferred treatment for status epilepticus, although Diazepam can also be used as an alternative.

Lorazepam has a longer duration of action than Diazepam, and binds with greater affinity to the GABA-A receptor subunit.

Phenobarbital is a barbiturate that acts on the GABA-A receptor site to increase the duration of chloride channel opening. Barbiturates, particularly phenobarbital, is considered the drug of choice for seizures in infants.

Phenytoin is a sodium-channel blocker that is given for generalized tonic-clonic seizures, partial seizures, and status epilepticus. Phenytoin is preferred in prolonged therapy for status epilepticus because it is less sedating.

Propofol or thiopentone is preferred when airway protection is required.

Elimination of phenytoin from the body follows first-order kinetics. This means that the rate of elimination is proportional to plasma concentration.

The rate of elimination can be described by the equation:

C = C0·e-kt

Where:

C = drug concentration
C0 = drug concentration at time zero (extrapolated)
k = Rate constant
t = Time

Enzyme systems become saturated when phenytoin concentrations exceed the normal range and elimination of the drug becomes zero-order. At this point, the drug is metabolised at a fixed rate and metabolism is independent of plasma concentration.

Aspirin and ethyl alcohol are other drugs that behave this way.

The renal arteries branch from the abdominal aorta just below the origin of the superior mesenteric artery. The right renal artery is higher and longer than the left renal artery. The left renal artery passes behind the left renal vein, the body of the pancreas, and the splenic vein.

The important landmarks of vessels arising from the abdominal aorta at different levels of vertebrae are:

T10 – oesophageal opening in the diaphragm

T12 – Coeliac trunk, aortic hiatus in the diaphragm

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

The hypothalamus is primarily responsible for the regulation of the basal metabolic rate. It releases thyrotropin releasing hormones (TRH) in response to low levels of triiodothyronine (T3) and thyroxine (T4). The TRH acts on the pituitary gland to release thyroid stimulating hormone, which will stimulate the thyroid gland to synthesize more T3 and T4.

Basal metabolic rate refers to the energy expended by an individual in a resting, post-absorptive state. It represents the energy required to carry out normal body functions, such as respiration.

Microshock refers to ventricular fibrillation caused by miniscule amounts of currents or voltages (100-150 microamperes) passing through the myocardial tissue from external cables arising from electrical components within the cardiac muscle, for example, pacemaker electrodes or saline filled venous catheters.
The risk of shock changes with the construction of electrical equipment in question. The main classes of electrical equipment include: I: Appliances have a protective earth connected to an outer casing which prevents live elements from coming in contact with conductive elements. A fault in this equipment class will result in live elements coming in contact with the outer casing and allowing electrical flow into the protective earth. This triggers the protective fuse to disconnect the electric supply to the appliance.
II: These appliances have reinforced insulation. In the event of a fault which causes the first layer of insulation to fail, the second layer is able to prevent contact of live elements with outer casing.
III: These appliances have no insulation to provide safety, and rely solely on the use of separated extra low voltage source (SELV) which limits voltage to 25V AC or 60V DC allowing for a person to come in contact with it without risk of a shock under normal dry conditions. Under wet conditions, voltage supply should be lowered to reduce risk of shock. These devices have no risk of macroshocks, but some risk of microshocks.
Class I and II electrical appliances are further divided into subtypes developed to limit current leakage in the event of a singular fault:
B (body): Upper limit of current leakage is 500 µA. This current can cause skin tingling and microshocks, but is not sufficient to cause injury.
BF (body floating): These appliances have an isolating capacitor or transformer which separate the secondary circuit from the protective earth. The upper limit of current leakage is the same as type B.
CF (cardiac floating): Upper limit of leakage current during a singular fault is 50 microamps. It is least likely to result in a microshock

A person remaining at high altitudes for days, weeks, or years becomes more and more acclimatized to the low PO2, so it causes fewer deleterious effects on the body.

After acclimatization, it becomes possible for the person to work harder without hypoxic effects or to ascend to still higher altitudes. The principal means by which acclimatization comes about are (1) a great increase in pulmonary ventilation, (2) increased numbers of red blood cells, (3) diffusing capacity of the lungs, (4) increased vascularity of the peripheral tissues, and (5) increased ability of the tissue cells to use oxygen despite low PO2.

The cardiac output often increases as much as 30% immediately after a person ascends to high altitude but then decreases back toward normal over a period of weeks as the blood haematocrit increases, so the amount of oxygen transported to the peripheral body tissues remains about normal.

With regards to the autonomic nervous system (ANS)

1. It is not under voluntary control
2. It uses reflex pathways and different to the somatic nervous system.
3. The hypothalamus is the central point of integration of the ANS. However, the gut can coordinate some secretions and information from the baroreceptors which are processed in the medulla.

With regards to the central nervous system (CNS)
1. There are myelinated preganglionic fibres which lead to the
ganglion where the nerve cell bodies of the non-myelinated post ganglionic nerves are organised.
2. From the ganglion, the post ganglionic nerves then lead on to the innervated organ.

Most organs are under control of both systems although one system normally predominates.

The nerves of the sympathetic nervous system (SNS) originate from the lateral horns of the spinal cord, pass into the anterior primary rami and then pass via the white rami communicates into the ganglia from T1-L2.

There are short pre-ganglionic and long post ganglionic fibres.
Pre-ganglionic synapses use acetylcholine (ACh) as a neurotransmitter on nicotinic receptors.
Post ganglionic synapses uses adrenoceptors with norepinephrine / epinephrine as the neurotransmitter.
However, in sweat glands, piloerector muscles and few blood vessels, ACh is still used as a neurotransmitter with nicotinic receptors.

The ganglia form the sympathetic trunk – this is a collection of nerves that begin at the base of the skull and travel 2-3 cm lateral to the vertebrae, extending to the coccyx.

There are cervical, thoracic, lumbar and sacral ganglia and visceral sympathetic innervation is by cardiac, coeliac and hypogastric plexi.

Juxta glomerular apparatus, piloerector muscles and adipose tissue are all organs under sole sympathetic control.

The PNS has a craniosacral outflow. It causes reduced arousal and cardiovascular stimulation and increases visceral activity.

The cranial outflow consists of
1. The oculomotor nerve (CN III) to the eye via the ciliary ganglion,
2. Facial nerve (CN VII) to the submandibular, sublingual and lacrimal glands via the pterygopalatine and submandibular ganglions
3. Glossopharyngeal (CN IX) to lungs, larynx and tracheobronchial tree via otic ganglion
4. The vagus nerve (CN X), the largest contributor and carries ¾ of fibres covering innervation of the heart, lungs, larynx, tracheobronchial tree parotid gland and proximal gut to the splenic flexure, liver and pancreas

The sacral outflow (S2 to S4) innervates the bladder, distal gut and genitalia.

The PNS has long preganglionic and short post ganglionic fibres.
Preganglionic synapses, like in the SNS, use ACh as the neuro transmitter with nicotinic receptors.
Post ganglionic synapses also use ACh as the neurotransmitter but have muscarinic receptors.

Different types of these muscarinic receptors are present in different organs:
There are:
M1 = pupillary constriction, gastric acid secretion stimulation
M2 = inhibition of cardiac stimulation
M3 = visceral vasodilation, coronary artery constriction, increased secretions in salivary, lacrimal glands and pancreas
M4 = brain and adrenal medulla
M5 = brain

The lacrimal glands are solely under parasympathetic control.

Propofol infusion syndrome is a rare but extremely dangerous complication of propofol administration

Common organ systems affected by PRIS include the following:
1. cardiovascular
widening of QRS complex, Brugada syndrome-like patterns (particularly type 1), ventricular tachyarrhythmias, cardiogenic shock, and asystole

2. hepatic
Liver enzymes elevation, hepatomegaly, and steatosis

3. skeletal muscular
myopathy and overt rhabdomyolysis

4. renal
Hyperkalaemia, acute kidney injury

5. metabolic
High anion gap metabolic acidosis (due to elevation in lactic acid)

The vertebral artery originates from the subclavian artery and ascends through the neck in the transverse foramen of the C1-C6 vertebrae. C2 vertebra is called the axis vertebra. A part of the vertebral artery lies in a groove on the upper surface of the atlas’s (C1) posterior arch. It enters the vertebral canal below the inferior border of the posterior atlantooccipital membrane. The vertebral arteries then enter the skull via the foramen magnum.

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.

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.

An acetylcholinesterase inhibitor or anticholinesterase is a chemical that inhibits the cholinesterase enzyme from breaking down acetylcholine (ACh) therefore increasing the level and duration of action of the neurotransmitter acetylcholine(ACh).

ACh stimulates postganglionic receptors to produce the following effects:

Salivation
Lacrimation
Defecation
Micturition
Sweating
Miosis
Bradycardia, and
Bronchospasm.

Since these effects are produced by muscarine, they are referred to as muscarinic effects, and the postganglionic receptors are called muscarine receptors.

SLUD (Salivation, Lacrimation, Urination, Defecation – and emesis) is usually encountered only in cases of drug overdose or exposure to nerve gases. It is a syndrome of pathological effects indicating massive discharge of the parasympathetic nervous system.

Oxygen delivery is related to blood flow as most of the oxygen binds to haemoglobin in red blood cells, although a small amount is dissolved in the plasma. Blood flow per 100 g of tissue is greatest in the kidneys.

The following is the oxygen consumption rate of different organs in ml/minute/100g

Hepatoportal = 2.2
Kidney = 6.8
Brain = 3.7
Skin = 0.38
Skeletal muscle = 0.18
Heart = 11

A prospective randomised double blind controlled trial against cyclizine in multiple centres is the most likely to change your practice.

Case controlled studies are efficient in identifying an association between a drug treatment and outcome and are usually conducted retrospectively. They are generally less valued than prospective randomised trials. They cannot generate incidence data, are subject to bias, have difficult selection of controls and can be made more difficult if note keeping is not reliable.

The gold standard in intervention-based studies is randomised controlled double blind trials. Its features are:

Treating all intervention groups identically
Reduction of bias by random allocation to intervention groups
Patients and researchers unaware of which treatment was given until at completion of study
Patients analysed within the group to which they were allocated, and
Analysis focused on estimating the size of the difference in predefined outcomes between intervention groups.

New healthcare interventions should be evaluated through properly designed randomised controlled trials (though there are some potential ethical disadvantages)

Conducting trials in multiple centres is an accepted way of evaluating a new drug as it may be the only way of recruiting sufficient number of patients within a reasonable time frame to satisfy the objectives of the trial. Type II statistical errors will occur if a small numbers of patients is used in study group.

An intra-operative air embolism occurs when air becomes trapped in the blood vessels during surgery.

A transoesophageal echocardiography (OE) uses invasive echocardiography to monitor the integrity and performance of the heart. It is the gold standard as it provides real-time imaging of the heart to enable early diagnosis and treatment.

Precordial doppler ultrasonography can also be used to detect into-operative air emboli. It is non-invasive and more practical, but is less sensitive.

A change in end-tidal CO2 could be indicative of and increase in physiological dead-space, but could also be indicative of any processes that reduces the excretion or increases the production of CO2, making it non-specific.

A transoesophageal stethoscope can be used to listen for the classic mill-wheel murmur produced by a large air embolus.

Mast cell tryptase is a reliable marker of mast cell degranulation. Tryptase is a protease enzyme that acts via widespread protease-activated receptors (PARs).

Magnesium is a very important cation due to its various physiological roles in the body. This includes:
– playing the role of a cofactor in many enzymatic reactions
– influencing hormone receptor binding
– affecting calcium channels
– impact on cardiac, vascular and neural cells

Magnesium sulphate is used as first line in the treatment of eclampsia. Moreover, it has some preventive role in patients with severe pre-eclampsia. All the clinical effects of magnesium are in line with its plasma concentration.

The first sign of magnesium toxicity in obstetric patients is the loss of patellar reflex, which is regularly monitored during treatment. The other options are all late signs of magnesium toxicity.

Whenever there is a doubt, serum magnesium levels should always be monitored.

The table below correlates the effects of increased levels of magnesium on the body:

Plasma Concentration
(mmol/L) Effect
0.7-1.2 Normal
4-8 Decreased deep tendon reflexes, nausea, headache, weakness, malaise, lethargy and facial flushing
5-10 ECG changes (prolonged PR, prolonged QT, and widened QRS)
10 Muscle weakness, loss of deep tendon reflexes, hypotension
15 SA/AV nodal block, respiratory paralysis and depression
20 Cardiac arrest

The cylindrical structure(spine), starts from the foramen magnum in medulla oblongata at the skull’s base. Its length varies in gender with men having 45cm and women having up to 43 cm. The spine contains 31 pairs of spinal nerves, named according to the spinal region:
– 8 cervical nerve pairs ( C1-C8)
– 12 thoracic nerve pairs ( T1-T12)
– 5 lumbar nerve pairs (L1-L5)
– 5 sacral nerves (S1-S5) and
– 1 coccygeal nerve pair.
These spinal nerves are classified as the peripheral nervous system though they branch from the spinal cord and central nervous system. They interact directly with the spinal cord to modulate the motor and sensory information from the peripheral’s region. As the nerves emerges form the spinal cords they are known as rootlets. They join to form nerve roots, and depending on their position, we have anterior nerve roots and posterior.

The spinal cord is supplied by two posterior and one anterior spinal arteries which anastomoses caudally, at the conus medullaris.

The anterior spinal artery supplies the anterior two-thirds of the spinal cord and medulla. Disruption of the anterior spinal artery supply is characterised by ischaemia or infarction of motor tracts (corticospinal) and loss of pain and temperature sensation below the level of the lesion.

The posterior spinal arteries supply the posterior columns (posterior third of the spinal cord). Infarction of the posterior columns results in the loss of proprioceptive, vibration and two-point discrimination.

The spinal cord normally ends at the level of L1 or L2 in an adult and L3 in a newborn.

The most common cause of hypoparathyroidism is injury or removing the parathyroid glands. They can be injured accidentally during surgery to remove the thyroid as they are located posterior to the thyroid gland.

A result of both low parathyroid hormone and low calcium is likely to mean that the parathyroid glands are not responding to hypocalcaemia. The hypocalcaemia can cause confusion, and the stay in the hospital is likely to refer to her surgery.

While a parathyroid adenoma is fairly common and can cause hypoparathyroidism, it much more likely causes hyperparathyroidism.

Chronic kidney disease is likely to cause hypocalcaemia, which would increase parathyroid hormone production in an attempt to increase calcium levels, causing hyperparathyroidism. Vitamin D is activated by the kidneys and then binds to calcium to be absorbed in the terminal ileum so that a deficiency would cause hyperparathyroidism.

The correct answer is the mean, median and mode of normally distributed data are the same value. This is as a result of the bell shaped curve which is equal on both sides.

The bell-shape indicates that values around the mean are more frequent in occurrence than the values farther away.

In a normal distribution:
1) +/- one standard deviation of the mean accounts for 68% of the data.
2) +/- two standard deviations of the mean accounts for 95% of the data.
3) +/- three standard deviations of the mean accounts for 99.7% of the data.

Among the breathing circuits, the Lack circuit is the most efficient for spontaneous breathing.

An outer coaxial tube is present to deliver fresh air; exhaust air is routed to an inner tube, which is then delivered to a scavenging system. An expiratory valve is seen at the patient end, which is an advantage over other circuits. Moreover, the Lack circuit prevents rebreathing slightly greater than the alveolar minute ventilation at 4-5 litres per minute.

The Bain circuit prevents rebreathing at 160-200ml/kg per minute, and is a co-axial version of the Mapleson D circuit.

The Mapleson E circuit prevent rebreathing at a fresh gas flow (FGF) of approximately twice the patient’s normal minute volume. A modification of this, the Mapleson F, has a reservoir bag at the opposite end for the FGF. This circuit is appropriate for paediatric patients with a body weight less than 20 kg.

Iron is a necessary micronutrient for proper erythropoietic function, oxidative metabolism, and cellular immune responses. Although dietary iron absorption (1-2 mg/d) is tightly controlled, it is only just balanced by losses.

The adult body contains 35-45 mg/kg iron (about 4-5 g)

Iron can be found in a variety of forms, including haemoglobin, ferritin, haemosiderin, myoglobin, haem enzymes, and transferrin bound proteins.

Low molecular weight heparin (LMWH) creates a complex by binding to antithrombin. This complex binds with and inactivates factor Xa.

There is less risk of bleeding with LMWH because it binds less to platelets, endothelium and von Willebrand factor.

LMW binds Xa more readily. The shorter chains are less likely to bind both antithrombin and thrombin.

There is need for monitoring in renal impairment because LMHW is excreted in the urine (and partly by hepatic metabolism)

LMWH have been shown to be as efficacious as unfractionated heparin. It is also safer and have improved inpatient stay and reduced hospital cost.

Small measurement units are denoted by the following SI mathematical prefixes:

1 deci = 0.1
1 milli = 0.001
1 micro = 0.000001
1 nano = 0.000000001
1 pico = 0.000000000001
1 femto = 0.000000000000001 (used to measure red blood cell volume)
1 atto = 0.000000000000000001

Certain skeletal muscles are more resistant to the effects of neuromuscular blocking agents, both non-depolarizing and depolarizing. The diaphragm is the most resistant. The muscles of the larynx and the corrugator supercilii are less resistant. The abdominal, orbicularis oris, and limb peripheral muscles are the most sensitive muscles.

Twitch stimulation patterns:

Supramaximal single stimulus:

The frequency ranges from 1 Hz to 0.1 Hz (one every second to one every 10 seconds)
The response is proportional to the frequency of the event.
It has limited clinical utility because it only tells you whether or not a patient is paralysed (no information on degree of paralysis).

Over the course of 0.5 seconds (2 Hz), four supramaximal stimulate were applied:

It is possible to see ‘fade’ and use it as a basis for evaluation.
This stimulation pattern is used to determine the degree of blockade (1-2 twitches is appropriate for abdominal surgery)
If the train of four (TOF) count is 1-2, reversal agents can be used in conjunction with medium-acting neuromuscular blocking agents.

Ratio of TOF:

This is the ratio of the 4th twitch amplitude to the 1st twitch amplitude.
The ratio decreases with non-depolarising block and is inversely proportional to the degree of block, allowing objective measurement of residual neuromuscular blockade.
To achieve adequate reversal, the ratio (as measured by accelerography) must be between 0.7 and 0.9.

Count of twitches after a tetanic experience(PTC):

50 Hz for 5 seconds, then a 3 second pause, followed by a single 1 Hz twitch stimulus.
When the TOF count is zero, this stimulation pattern is used to assess deep blockade (that is, in neurosurgery, microsurgery or ophthalmic surgery when even small movements of a patient will disturb the surgical field)
It gives an estimate of how long it will take for the response to return to single twitches, allowing assessment of blocks that are too deep for any other technique.
A palpable post-tetanic count (PTC) of 2 indicates no twitch response for about 20-30 minutes, and a PTC of 5 indicates no twitch response for about 10-15 minutes.

This is without a doubt the best way to keep track of paralysis in patients who need to avoid diaphragmatic movement. It’s best to use drug infusions and aim for a PTC of 2. After a tetanic stimulus, acetylcholine is mobilised, causing post-tetanic potentiation.

Stimulation in Two Bursts:

750 milliseconds between two short bursts of 50 Hz
This stimulation pattern is used to assess small amounts of residual blockade manually (tactile).

The clinical picture best describes a probable drug interaction with pethidine.

Phenelzine, a monoamine oxidase (MAO) inhibitor, when given with pethidine, an opioid analgesic, may lead to episodes of hypertension, rigidity, excitation, hyperpyrexia, seizures, coma and death. Studies have shown that pethidine reacts more significantly with MAO inhibitors than morphine.

When pethidine is metabolised to normeperidine, it acts as a serotonin reuptake inhibitor and cause an increase in serotonin levels in the brain. MAO inhibitors can also lead to elevated levels of serotonin because of its mechanism of action by inhibiting the enzyme monoamine oxidase that degrades serotonin.

The excess serotonin levels may lead to serotonin syndrome, of which some of the common precipitating drugs are selective serotonin reuptake inhibitors, MAO inhibitors, tricyclic antidepressants, meperidine, and St. John’s Wort. Onset of symptoms is within hours, which includes fever, agitation, tremor, clonus, hyperreflexia and diaphoresis.

Drug interaction between phenelzine and paracetamol do not commonly precipitate serotonin syndrome.

Neuroleptic malignant syndrome is due to dopamine antagonism, precipitated commonly by antipsychotics. Its onset of symptoms occur in 1 to 3 days, and is characterized by fever, encephalopathy, unstable vitals signs, elevated CPK, and rigidity.

Altered mental status is the most common manifestation of sepsis-associated encephalopathy. Patient also exhibit confusional states and inappropriate behaviour. In some cases, this may lead to coma and death.