Ambient pressure has no effect on a volatile agent’s saturated vapour pressure (SVP). At a temperature of 20°C, the SVP of sevoflurane is approximately 21 kPa, or 21% of atmospheric pressure (100 kPa).

The SVP of sevoflurane remains the same when the ambient pressure is doubled to 200 kPa, but the output of the vaporiser is halved, now 21 percent of 200 kPa, equalling 10.5 percent. The vaporiser’s output has increased to 1%, but the partial pressure output has remained unchanged. The splitting ratio will not change because it is determined by temperature changes.

Calculations can be made as follows:

Vaporizer output % (ambient pressure) = % volatile (calibrated) x 100 kPa calibrated pressure/ambient pressure
2% = 2% (dialled) × 100/100
2% of 100 = 2 kPa

Altitude, pressure 50 kPa
4% = 2% (dialled) × 100/50
4% of 50 = 2 kPa

High pressure at 200 kPa
1% = 2% (dialled) × 100/200
1% of 200 = 2 kPa

Sevoflurane has a boiling point of 58°C and, unlike desflurane (which has a boiling point of 22.8°C), does not need to be heated and pressurised with a Tec 6 vaporiser.

Linear regression, using a technique called curve fitting, allows us to make predictions regarding a certain variable.

Correlation coefficient gives us an idea whether or not the two parameters provide have any relation of some sort or not i.e. does change in one prompt any change in other?

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

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

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

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

Thiopental is a new British Approved Name for thiopentone and is thio-barbiturate.
Methohexitone is an oxy- barbiturate. Both thiopental and methohexitone are intravenous induction agents.

Ketamine cannot cause loss of consciousness in less than 30 seconds. At least 30 seconds is needed to cause loss of consciousness following intravenous administration.

Etomidate is an imidazole but it is not used in the Intensive Care unit for sedation because it has an antidepressant effect on the steroid axis.

Severity of a reduction in restrictive defect (%FVC) or obstructive defect (%FEV1/FVC) predicted are classified as follows:

Mild 70-80%
Moderate 60-69%
Moderately severe 50-59%
Severe 35-49%
Very severe <35% This patient has a %FVC predicted of 60.4% and this corresponds to a moderate restrictive deficit. %FEV1/FVC ratio is 93.5%. FEV1/FVC ratio 80% < predicted and VC < 80% = mixed picture. FEV1/FVC ratio 80% < predicted and VC > 80% = obstructive picture.

FEV1/FVC ratio 80% > predicted and VC > 80% = normal picture.

FEV1/FVC ratio 80% > predicted and VC < 80% predicted= restrictive picture. The integrity of the alveolar-capillary barrier is measured by carbon monoxide transfer factor (TLCO) and carbon monoxide transfer coefficient (KCO). These values are seen to be reduced in emphysema, interstitial lung diseases and in pulmonary vascular pathology. However, the KCO (as % predicted) is high in extrapulmonary restriction (pleural, chest wall and respiratory neuromuscular disease), and in loss of lung units provided the structure of the lung remaining is normal. The KCO distinguishes extrapulmonary (high KCO) causes of ‘restriction’ from intrapulmonary causes (low KCO).

Hydrochloric acid is lost when you vomit for a long time (HCl). As a result, the following can be expected, in varying degrees of severity:

Hypokalaemia
Hypochloraemia
Increased bicarbonate to compensate for chloride loss and metabolic alkalosis

The alkalosis causes potassium to move from the intracellular to the extracellular compartment at first. Long-term vomiting and dehydration cause potassium to be excreted by the kidneys in order to conserve sodium. Dehydration can cause urea and creatinine levels to rise.

The actual base excess is always greater than the standard base excess.

The actual base excess (BE) is a measurement of a base’s contribution to a blood gas picture’s metabolic component. It’s the amount of base that needs to be added to a blood sample to bring the pH back to 7.4 after the respiratory component of a blood gas picture has been corrected (PaCO2 of 40 mmHg or 5.3 kPa). The BE has a normal range of +2 to 2. A large positive BE indicates a severe metabolic alkalosis, while a large negative BE indicates a severe metabolic acidosis. As a result, the actual BE in vitro is unaffected by CO2.

In vivo, however, standard BE is not independent of pCO2 because blood with haemoglobin acts as a better buffer than total ECF.

As a result, it is impossible to tell the difference between compensating for a respiratory disorder and compensating for the presence of a primary metabolic disorder.

The differences between in vitro and in vivo behaviour can be mostly eliminated if the BE is calculated for a haemoglobin concentration of 50 g/L (the ‘effective’ or virtual value of Hb if it was distributed throughout the extracellular space) rather than the actual haemoglobin. Because haemoglobin has a lower buffering capacity, the standard BE is higher than the actual BE. It reflects the BE better in the extracellular space rather than just the intravascular compartment.

Mivacurium is metabolised primarily by plasma cholinesterase at an In vitro rate of about 70% that of succinylcholine. Mivacurium is contraindicated in patients with genetic and acquired plasma cholinesterase deficiencies.

The clearance of atracurium is by Hoffman degradation and ester hydrolysis in the plasma and is independent of both hepatic and renal function.

Rocuronium is eliminated primarily by the liver after metabolises to a less active metabolite, 17-desacetyl-rocuronium. Its duration of action is not affected much by renal impairment.

Vecuronium undergoes hepatic metabolism into 3-desacetyl-vecuronium which has 50-80% the activity of the parent drug. It undergoes biliary (40%) and renal excretion (30%). The aminoglycoside antibiotics possess additional neuromuscular blocking activity. The potency of gentamicin > streptomycin > amikacin. Calcium can be used to reverse the muscle weakness produced by gentamicin but not neostigmine. When vecuronium and gentamycin are given together the effect on neuromuscular blockade is synergistic.

Significant residual neuromuscular block 2 hours after the administration of these drugs is unlikely In this scenario.

Any recovery from neuromuscular blockade with suxamethonium in a patient with deficiency of plasma cholinesterase demonstrate four twitches on a train of four count.

Standard error can be calculated by the following formula:

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

pH=7.36, PaCO2=8.5kPa, PaO2=7.5kPa, HCO3- = 43mmol/L is the correct answer.

Since the pH is the lower limit of normal, it is compensated despite a raised PaCO2. Retention of bicarbonate ions by the renal system suggests this process is chronic.

pH=7.24, PaCO2=3.5kPa, PaO2=8.5kPa, HCO3- =18mmol/L represents an acute uncompensated metabolic acidosis

The remaining stems are degrees of uncompensated respiratory acidosis and therefore incorrect.

There are two types of drug dose-response relationships, namely, the graded dose-response and the quantal dose-response relationships.

Drug response curves are plotted as percentage response again LOG drug concentration. This graph is sigmoid in shape.

Agonists are drugs with high affinity and high intrinsic activity. Meanwhile, the antagonist is a drug with high affinity but no intrinsic activity. Intrinsic activity determines the maximal response. The maximal response can be achieved even by activation of a small proportion of receptor sites.

While the brain only weighs 3% of the body weight, 15% of the cardiac output goes towards the brain.

Between mean arterial pressures (MAP) of 60-130 mmHg, autoregulation of cerebral blood flow (CBF) occurs. Exceeding this, the CBF is maintained at a constant level. This is controlled mainly by the PaCO2 level, and the autonomic nervous system has minimal role.

Beyond these limits, the CBF is directly proportional to the MAP, not the systolic blood pressure.

The posterior tibial nerve lies on the posterior surface of the tibialis posterior and, lower down the leg, on the posterior surface of the tibia. The nerve accompanies the posterior tibial artery and lies at first on its medial side, then crosses posterior to it, and finally lies on its lateral side. The nerve, with the artery, passes behind the medial malleolus, between the tendons of the flexor digitorum longus and the flexor hallucis longus.

It gives off muscular branches to the soleus, flexor digitorum longus, flexor hallucis longus, and tibialis posterior. A medial calcaneal branches off to supply the skin over the medial surface of the heel, and an articular nerve to supply the ankle joint. Finally, it terminates to become the medial and lateral plantar nerves.

The saphenous nerve is a branch of the femoral nerve that gives off branches that supply the skin on the posteromedial surface of the leg.

The sural nerve is a branch of the tibial nerve that supplies the skin on the lower part of the posterolateral surface of the leg.

The superficial peroneal nerve is one of the terminal branches of the common peroneal nerve. It arises in the substance of the peroneus longus muscle on the lateral side of the neck of the fibular. It ascends between the peroneus longus and brevis muscles, and in the lower part of the leg it becomes cutaneous. Muscular branches of the superficial peroneal nerve supply the peroneus longus and brevis muscles, while medial and lateral cutaneous branches are distributed to the skin on the lower part of the leg and dorsum of the foot. In addition, the cutaneous branches supply the dorsal surfaces of the skin of all the toes, except the adjacent sides of the first and second toes and the lateral side of the little toe.

The superficial peroneal, sural and saphenous nerves cannot be used to assess neuromuscular blocks since they are sensory nerves.

The deep peroneal nerve enters the dorsum of the foot by passing deep to the extensor retinacula on the lateral side of the dorsalis pedis artery. It divides into terminal, medial, and lateral branches. The medial branch supplies the skin of the adjacent sides of the big and second toes. The lateral branch supplies the extensor digitorum brevis muscle. Both terminal branches give articular branches to the joints of the foot. This nerve is too deep to use for neuromuscular blockade assessment

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 ventilatory anaerobic threshold (VAT), formerly referred to as the anaerobic threshold, is an index used to estimate exercise capacity. During the initial (aerobic) phase of CPET, which lasts until 50–60% of Vo2max is reached, expired ventilation (VE) increases linearly with Vo2 and reflects aerobically produced CO2 in the muscles. Blood lactate levels do not change substantially during this phase, since muscle lactic acid production is minimal.

During the latter half of exercise, anaerobic metabolism occurs because oxygen supply cannot keep up with the increasing metabolic requirements of exercising muscles. At this time, there is a significant increase in lactic acid production in the muscles and in the blood lactate concentration. The Vo2 at the onset of blood lactate accumulation is called the lactate threshold or the VAT. The VAT is also defined as the point at which minute ventilation increases disproportionately relative to Vo2, a response that is generally seen at 60–70% of Vo2max.

The VAT is a useful measure as work below this level encompasses most daily living activities. The ability to achieve the VAT can help distinguish cardiac and non‐cardiac (pulmonary or musculoskeletal) causes of exercise limitation, since patients who fatigue before reaching VAT are likely to have a non‐cardiac problem.

When VAT is detected, patients with PVo2 of ⩽10 ml/kg/min have a high event rate.

The cephalic vein is one of the primary superficial veins of the upper limb. The superficial group of upper limb veins begin as an irregular dorsal arch on the back of the hand.

The cephalic vein originates in the anatomical snuffbox from the radial side of the arch and travels laterally up, within the superficial fascia to join the basilic vein via the median cubital vein at the elbow.

Near the shoulder, it passes between the deltoid and pectoralis major muscles. It pierces the coracoid membrane (continuation of the clavipectoral fascia) to terminate in the axillary vein’s first part.

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

Standard error can be calculated by the following formula:
Standard Error= (Standard Deviation)/√(Sample Size)
= (16) / √(100)
= 16 / 10
= 1.6

The following are the colour codes for medical gas cylinders:

Oxygen cylinder has a dark body with white shoulders.

Nitrous oxide is French blue. Air encompasses a grey body with dark and white quarters on the shoulders.

Entonox contains a French blue body with white and blue quarters on the shoulders.

Carbon dioxide barrels are grey in colour.

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

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

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

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

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

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

The osmolar gap (OG) is calculated as follows:

OG = osmolaRity calculated from measured serum osmolaLity

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

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.

Penicillinase is a narrow spectrum ?-lactamase that 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.

N. meningitidis is sensitive to penicillin and less than 20% resistance is found in pseudomonas.

The liver receives blood supply from two sources.
1. Hepatic artery proper
It arises from the celiac trunk via the common hepatic artery and brings oxygenated blood to the liver.
It contributes to approximately 30% of the blood supply of the liver.
2. Hepatic portal vein – supplies the liver with partially deoxygenated blood, carrying nutrients absorbed from the small intestine. It gets tributaries from the inferior mesenteric vein, splenic vein, and superior mesenteric vein

The inferior mesenteric artery supplies the hindgut.
The superior mesenteric artery supplies the pancreas and intestine up to the proximal two-thirds of the transverse colon.
The inferior phrenic artery supplies the inferior surface of the diaphragm and oesophagus.

The Beers criteria, a US set of criteria for good prescribing in the older patient, preclude the use of metoclopramide in Parkinson’s disease. The Adverse Reactions Register of the UK Committee on Safety of Medicines (CSM) for the years 1967 to 1982 contained 479 reports of extrapyramidal reactions in which metoclopramide was the suspected drug; 455 were for dystonic-dyskinetic reactions, 20 for parkinsonism and four for tardive dyskinesia. Effects can occur within days of initiation of treatment and may take months to wear off.

Other antiemetics are available, such as cyclizine (Valoid), domperidone and ondansetron, which would be more appropriate to use in those with Parkinson’s disease.

Cyclizine is a piperazine derivative with histamine H1 receptor antagonist and anticholinergic activity. It is used for the treatment of nausea, vomiting, (particularly opioid-induced vomiting), vertigo, motion sickness, and labyrinthine disorders.

Prochlorperazine is an antipsychotic known to cause tardive dyskinesia, tremor and parkinsonian symptoms and is therefore likely to exacerbate Parkinson’s disease. Prochlorperazine is not favoured for older patients because of the increased risk of stroke and transient ischaemic attack (TIA).

Droperidol and phenothiazine are also potent antagonists on D2 receptors and must also be avoided.

Prednisolone 5 mg is the same as 20 mg hydrocortisone.

Prednisolone 40 mg is the same as 8 x 20 mg or 160 mg of prednisolone.

Mineralocorticoid effects and variations in action duration are not taken into account in these comparisons.

5 mg of prednisolone is the same as Dexamethasone 750 mcg, Hydrocortisone 20 mg, Methylprednisolone 4 mg, and Cortisone acetate 25 mg.

The heart has two venous drainage systems:
1. Greater venous system – it parallels the coronary arterial circulation and provides 70% venous drainage to the heart
2. Lesser venous system – includes the thebasian veins and provides up to 30% of the venous drainage to the heart

Thebasian veins (also called venae cordis minimae) are the smallest coronary veins and run in the myocardial layer of the heart. They serve to drain the myocardium and are present in all four heart chambers. They are more abundant on the right side of the heart and, more specifically, are most abundant in the right atrium. Thebesian veins drain the subendocardial myocardium either directly, via connecting intramural arteries and veins, or indirectly, via subendocardial sinusoidal spaces.

After thyroid surgery, about 10-15% of patients experience a temporary subjective voice change of varying degrees. A frog in the throat or cracking of the voice, or a weak voice, are common descriptions. These modifications are only temporary, lasting a few days to a few weeks.

Swelling of the muscles in the area of the dissection, as well as inflammation and oedema of the larynx due to the dissection, or minor trauma from the tracheal tube, are all suspected causes.

On both sides of the thyroid gland, the superior laryngeal nerve (EBSLN) runs along the upper part. The muscles that fine-tune the vocal cords are innervated by these nerves. The quality of their voice is usually normal if they are injured, but making high-pitched sounds may be difficult. Injury to the EBSLN occurs in about 2% of the population.

Injuries to the recurrent laryngeal nerve (RLN) have been reported to occur in 1 percent to 14 percent of people. Except for the cricothyroid muscle, the RLN supplies all of the laryngeal intrinsic muscles.

This complication is usually unilateral and temporary, but it can also be bilateral and permanent, and it can be intentional or unintentional. The most common complication following thyroid surgery is a permanent lesion of damaged RLN, which manifests as an irreversible phonation dysfunction.

The crico-arytenoid joint dislocation is a relatively uncommon complication of tracheal intubation and blunt neck trauma. The probability is less than one in a thousand.

Vocal cord polyps affect 0.8 percent of people.

Approximately 20% of halothane and 0.02% desflurane undergo hepatic biotransformation. Desflurane, halothane, and isoflurane are metabolised in the liver by cytochrome p450 to trifluoroacetate. Through an immunological mechanism involving trifluoroacetyl hapten formation, trifluoroacetate is thought to be responsible for hepatotoxicity.

Potency of inhaled anaesthetic agents is measured using the minimal alveolar concentration (MAC). The MAC of halothane is 0.74% while that of desflurane is 6.3%. The potency can also be compared using the oil: gas partition coefficient (224 and 18.7 for halothane and desflurane respectively).

Onset of action of volatile agents depends on the blood:gas partition coefficient. A lower blood:gas partition coefficient and insolubility in blood means faster onset and offset of action. The blood gas coefficient for halothane is 2.4 while that of desflurane is 0.42. Desflurane is less soluble than halothane in blood. Halothane has a pungent smell that can irritate the airway which limits its use for a gaseous induction especially in paediatric anaesthesia. desflurane is not pungent.

Desfluranes boiling point is only slightly above normal room temperature (22.8°C) making it extremely volatile while the boiling point of halothane is approximately 50.2°C.

Prilocaine is the drug of choice for intravenous regional anaesthesia. 0.5% prilocaine (40 ml) is indicated for this condition.
Lidocaine is another alternative for this condition but volume and dose are likely to be inadequate for the procedure.

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.

There are different effects of electrocution and these can be shown in the table below.

Current Effect
1 mA Tingling
5 mA Pain
15 mA Tonic muscle contraction
50 mA Respiratory arrest
100 mA Ventricular fibrillation and cardiac arrest

The adrenal (suprarenal) gland is composed of two main parts: the adrenal cortex, which is the largest and outer part of the gland, and the adrenal medulla. The adrenal cortex consists of three zones: 1. Zona glomerulosa (outermost layer) is responsible for the production of mineralocorticoids, mainly aldosterone, which regulates blood pressure and electrolyte balance. 2. Zona fasciculata (middle layer) is responsible for the production of glucocorticoids, predominantly cortisol, which increases blood sugar levels via gluconeogenesis, suppresses the immune system, and aids in metabolism. It also produces 11-deoxycorticosterone and corticosterone in addition to cortisol. 3. Zona reticularis (innermost layer) is responsible for the production of gonadocorticoids, mainly dehydroepiandrosterone (DHEA), which serves as the starting material for many other important hormones produced by the adrenal gland, such as oestrogen, progesterone, testosterone, and cortisol. It is also responsible for administering these hormones to the reproductive regions of the body.

The adrenal medulla majorly secretes epinephrine (adrenaline), and norepinephrine in small quantity. Both hormones have similar functions and initiate the flight or fight response.

Catecholamine is mediated by cholinergic nicotinic transmission through changes in sympathetic nervous system (T5 – T11), being increased during stress and hypoglycaemia.

Blood supply to the adrenal gland is by these three arteries: superior suprarenal arteries, middle suprarenal artery and inferior suprarenal artery. Venous drainage is via the suprarenal vein to the left renal vein or directly to the inferior vena cava on the right side. There is no portal (venous) system between cortex and medulla.

The internal laryngeal nerve provides sensory innervation to the laryngeal mucosa, and injury to it will cause loss of sensation.

The internal laryngeal nerve lies inferior to the piriform recess mucous membrane, placing it at high risk of irritation or damage by objects which become lodged in the recess.

The internal laryngeal artery branches off the superior laryngeal artery accompanied by the superior laryngeal nerve, inferior to the thyroid artery which branches off the superior thyroid artery close to its bifurcation from the external carotid artery.

Phase 2 trials involve patients that are suffering from the disease under study and are associated with determining the efficiency and the optimum dosage of the drug.

Phase 0 trials assist the scientists in studying the behaviour of drugs in humans by micro dosing patients. They are used to speed up the developmental process. They have no measurable therapeutic effect and efficiency.

Phase 1 is associated with assessing whether a drug is safe to use or not. The process is extensive and can take up to several months. It also involves healthy participants (less than 100) that are paid to take part in the study. The side effects upon increasing dosage are also addressed by the study. The effects the drug has on humans including how its absorbed, metabolized and excreted are studied. Approximately 70% of the drugs pass this phase.

A ‘double blind crossover study’ happens when every patient receive both treatments.

It is incorrect to say that only half of the patients do not know which treatment they receive because in a double blind placebo control clinical trial ALL of the patients are blind to their treatment choice .

If some of the patients are not treated, they would be aware that they were not being treated and it could not be considered a blind trial.

In a double blind placebo control clinical trial both the clinician and the patient are blind to the treatment choice. The clinician assessing the effects of the treatment, therefore, does not know which treatment the patient has been given.

The null hypothesis states that there is no significant difference between two groups.

The alternative hypothesis states that there is a significant difference between two groups.

A type I error (false positive) occurs when a null hypothesis is rejected when it should be accepted.

A type II error (false negative) occurs when the alternative hypothesis is rejected when it should be accepted.

The probability determines the rejection of a null hypothesis.

The level of significance is set at p <0.05.

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.

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.

Moderately high doses of dopamine produce a positive inotropic (direct?1 and D1 action + that due to Noradrenaline 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.

With regards to compensatory response to blood loss, the following sequence of events take place:

1. Decrease in venous return, right atrial pressure and cardiac output
2. Baroreceptor reflexes (carotid sinus and aortic arch) are immediately activated
3. There is decreased afferent input to the cardiovascular centre in medulla. This inhibits parasympathetic reflexes and increases sympathetic response
4. This results in an increased cardiac output and increased SVR by direct sympathetic stimulation. There is increased circulating catecholamines and local tissue mediators (adenosine, potassium, NO2)
5. Fluid moves into the intravascular space as a result of decreased capillary hydrostatic pressure absorbing interstitial fluid.

A slower response is mounted by the hypothalamus-pituitary-adrenal axis.
6. Reduced renal blood flow is sensed by the intra renal baroreceptors and this stimulates release of renin by the juxta-glomerular apparatus.
7. There is cleavage of circulating Angiotensinogen to Angiotensin I, which is converted to Angiotensin II in the lungs (by Angiotensin Converting Enzyme ACE)

Angiotensin II is a powerful vasoconstrictor that sets off other endocrine pathways.
8. The adrenal cortex releases Aldosterone
9. There is antidiuretic hormone release from posterior pituitary (also in response to hypovolaemia being sensed by atrial stretch receptors)
10. This leads to sodium and water retention in the distal convoluted renal tubule to conserve fluid
Fluid conservation is also aided by an increased amount of cortisol which is secreted in response to the increase in circulating catecholamines and sympathetic stimulation.

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 follicle is the functional unit of the thyroid gland. The follicular cells surround the follicle which is filled with colloid. Suspended within the colloid is the is a pro-hormone complex thyroglobulin.

The synthesis and storage of thyroid hormones is done by follicular cells and the thyroglobulin within the colloid.

Iodide ions (I−) are actively transported against a concentration gradient into the follicular cell under the influence of thyroid stimulating hormone (TSH). It then undergoes oxidation to active iodine catalysed by thyroid peroxidase (TPO). The synthesis of thyroglobulin is in the follicular cells and it contains up to 140 tyrosine residues. The tyrosine residues of thyroglobulin and active iodine are merged to form mono- and di-iodotyrosines (MIT and DIT). The iodinated thyroglobulin is then taken up into the colloid where it is stored and dimerised. Two DIT molecules are joined to produce thyroxine (T4) while one MIT and one DIT molecule are joined to produce tri-iodotyrosine (T3) by a process catalysed by TPO.

Thyroglobulin droplets are taken up as vesicles into follicular cells by pinocytosis. This process is stimulated by TSH. When these vesicles fuse with lysosomes, hydrolysis of the thyroglobulin molecules and subsequent release of T4 and T3 into the circulation occurs.

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

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

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

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

There are different types of temperature measurement. These include:

Thermistor – this is a type of semiconductor, meaning they have greater resistance than conducting materials, but lower resistance than insulating materials. There are small beads of semiconductor material (e.g. metal oxide) which are incorporated into a Wheatstone bridge circuit. As the temperature increases, the resistance of the bead decreases exponentially

Thermocouple – Two different metals make up a thermocouple. Generally, in the form of two wires twisted, welded, or crimped together. Temperature is sensed by measuring the voltage. A potential difference is created that is proportional to the temperature at the junction (Seebeck effect)

Platinum resistance thermometers (PTR) – uses platinum for determining the temperature. The principle used is that the resistance of platinum changes with the change of temperature. The thermometer measures the temperature over the range of 200°C to1200°C. Resistance in metals show a linear increase with temperature

Tympanic thermometers – uses infrared radiation which is emitted by all living beings. It analyses the intensity and wavelength and then transduces the heat energy into a measurable electrical output

Gauge/dial thermometers – Uses coils of different metals with different co-efficient of expansion. These either tighten or relax with changes in temperature, moving a lever on a calibrated dial.

The normal distribution is a symmetrical, bell-shaped distribution in which the mean, median and mode are all equal.

Entonox is a gas that consists of 50% oxygen and 50% Nitrous oxide. Nitrous oxide is sometimes used for anaesthetics but in this combination, it works as a short-acting painkiller.

Under normal working conditions, it exists only in gaseous form in a cylinder. The gauge pressure of a full Entonox cylinder is 137 bar.

Entonox cylinders should be stored horizontally at a temperature above 0 C. At temperatures below this the nitrous oxide component may separate.

Pseudocritical temperature and pseudocritical pressure can be defined as the molal average critical temperature and pressure of mixture components. In other words, the pseudo-critical temperature is the temperature at which the two gases separate. The pseudo-critical temperature of Entonox is approximately -5.50 C

The first line of defence against acid-base disorder is buffering. The blood mainly utilizes bicarbonate ion (HCO3-) for its buffering capacity (total of 53%, plasma and red blood cells combined).

Strong acids, when acted upon by a buffer, release H+, which then combines to HCO3- and forms carbonic acid (H2CO3). When acted upon by the enzyme carbonic anhydrase, H2CO3 dissociates into H2O and CO.

The rest are the percentage of utilization for the following buffers:
Haemoglobin (by RBCs) – 35%
Plasma proteins (by plasma) – 7%
Organic phosphates (by RBCs) – 3%
Inorganic phosphates (by plasma) – 2%

Only on rare occasions has it been found that the prevalence and incidence were same. Incidence can be greater than prevalence in acute cases only. In case of chronic diseases prevalence is far greater than incidence. One needs to have a deeper understanding of both the concepts to understand the health literature.

30mL 0.5% bupivacaine, 1mL 1 in 1,000 adrenaline and 89mL 0.9% N. Saline is the correct answer.
Initial concentration of bupivacaine is 0.5% with a volume of 30mL

The volume is doubled (60mL) by the addition of 0.9% N. saline (30mls) and the concentration of bupivacaine is halved to (0.25%).

If the volume is doubled again (120mL) by the addition of further 0.9% N. saline (59mls) the final concentration of bupivacaine is halved again to 0.125%. Total N. saline = 89mls

The 1 mL of 1 in 1000 adrenaline has also been diluted into the final volume of 120 mL making it a 1 in 120000 concentration.

The tracheobronchial tree is subdivided into the conducting and the respiratory zones.

The zones from proximal to distal are:

Trachea
Bronchi
Bronchioles
Terminal bronchioles
Respiratory bronchioles
Alveolar ducts
Alveolar sacs

from the trachea to terminal bronchioles are the conducting zone while the respiratory zone is from the respiratory bronchioles to the alveola sacs

Number needed to treat (NNT) is a time specific epidemiological measure that indicates how many patients would be require for an intervention to prevent one additional bad outcome. A perfect NNT would be 1, where everyone improves with treatment, thus the higher the NNT, the less effective the treatment.

Thus if you treat 1000 patients then you will expect to have 50 fewer strokes.

The extrinsic pathway is considered as the main pathway of coagulation cascade.

Heparin is known to inhibit the activation of coagulation factors 2,9,10, and 11.

The extrinsic and intrinsic pathways meet at the activation of coagulation factor 10.

Fibrinogen is converted into Fibrin in the presence of Thrombin. Plasminogen is converted into plasmin during fibrinolysis to breakdown fibrin clot.

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.

The incidence of a disease is the number of new cases of the disease in a population over a defined time period.

The prevalence of a disease is the number of cases of the disease in a population over a defined time period describes. It is NOT the number of new cases.

The number of new cases of a disease only, has no denominator (time period or population) from which to derive an incidence.

The number of new cases of a disease seeking medical treatment is the incidence of patients seeking medical treatment NOT the incidence of the disease in a population.

The death rate from a disease is the number of patients dying from the disease in a population.

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.

Erythromycin binds to the 50s subunit of bacterial rRNA complex and inhibits protein synthesis.

Gentamicin is a broad-spectrum antibiotic whose mechanism of action involves inhibition of protein synthesis by binding to 30s ribosomes. Its major adverse effect is nephrotoxicity and ototoxicity

Aminoglycoside bind to 30s subunit of ribosome causing misreading of mRNA

Tetracyclines inhibit protein synthesis through reversible binding to bacterial 30s ribosomal subunits, which prevent binding of new incoming amino acids (aminoacyl-tRNA) and thus interfere with peptide growth.

The AV node has an intrinsic firing rate of 40-60 beats per minute which is clinically significant in cases of damage to the conducting pathways as patients continue to have a ventricular rate of 40-60. Patients who have an AV node supplied by the right coronary are said to be right dominant. The remaining 10% are left dominant and supplied by the left circumflex.

The right coronary artery supplies the right atrium, right ventricle, interatrial septum, and the inferior posterior third of the interventricular septum. It also supplies the atrioventricular node + sinoatrial node in most patients. The posterior descending artery supplies the posterior third of the interventricular septum.

The heart receives blood supply from coronary arteries. The right and left coronary arteries branch off the aorta and supply oxygenated blood to all heart muscle parts.

The left main coronary artery branches into:
1. Circumflex artery – supplies the left atrium, side, and back of the left ventricle. The left marginal artery arises from the left circumflex artery. It travels along the obtuse margin of the heart.
The left marginal artery, a branch of the circumflex artery, supplies the left ventricle.
2. Left Anterior Descending (LAD) artery – supplies the front and bottom of the left ventricle and front of the interventricular septum

The right coronary artery branches into:
1. Right marginal artery
2. Posterior descending artery

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.

Since the gas is less dense at higher altitudes, the density of a gas influences flows when passing through the orifice. Due to this reason, for a given flow rate, the bobbin will not be forced as far up the rotameter tube.

At higher altitudes, the volume of a fixed mass of gas increases, and therefore the molecules of gas are widely spaced resulting in a decrease in density with an increase in altitude.

Viscosity is simply termed as friction of gas. The viscosity of a gas is important only at low flow rates when the flow characteristic of the gas is laminar.

Charle’s law stated that the volume occupied by a fixed amount of gas is directly proportional to its absolute temperature (T) provided the pressure remains constant.

Boyle’s law for a fixed amount of gas at constant temperature, the pressure (P) and volume (V) are inversely proportional.

The prostate gland is primarily supplied by the inferior vesical artery, which branches off from the anterior division of the internal iliac artery. The inferior vesical artery supplies the base of the bladder, the distal ureters, and the prostate. The branches to the prostate communicate with the corresponding vessels of the opposite side.

The inferior vesical artery branches into two main arteries:
1. Urethral artery – supplies the transition zone and is the main arterial supply for the adenomas in BPH
2. Capsular artery – supplies the glandular tissue

The venous drainage of the prostate is from the prostatic venous plexus, which drains into the paravertebral veins.

The arch of aorta gives rise to three main branches:
1. Brachiocephalic artery
2. Left common carotid artery
3. Left subclavian artery

The brachiocephalic artery then gives rise to the right subclavian artery and the right common carotid artery.

The right common carotid artery arises from the brachiocephalic trunk posterior to the sternoclavicular joint.

The coeliac trunk is a branch of the abdominal aorta.
The ascending aorta supplies the coronary arteries.

Omitted variable bias occurs when a statistician passes over one or more relevant variables from the study.

Publication bias occurs in publish academic research. it occurs when the results of the study effect the decision whether to publish or not.

Expectation bias occurs when the expectation of a researcher about the results effect the behaviour of the participants. Expectations may come from communication and experiences.

Work up bias occurs in the study of diagnostic test validity, whether a gold standard procedure has been used. work up bias can seriously affect the specificity of the test.

Recall bias introduced when participants in a study are systematically more or less likely to recall and relate information on exposure depending on their outcome status. Recall bias is more potential for Case-control studies.

The diaphragm divides the thoracic cavity from the abdominal cavity. Structures penetrate the diaphragm at different vertebral levels through openings in the diaphragm to communicate between the two cavities. The diaphragm has openings at three vertebral levels:

T8: vena cava, terminal branches of the right phrenic nerve
T10: oesophagus, vagal trunks, left anterior phrenic vessels, oesophageal branches of the left gastric vessels
T12: descending aorta, thoracic duct, azygous and hemi-azygous vein

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

The neuroleptic malignant syndrome (NMS) is a rare complication in response to neuroleptic or antipsychotic medication.

The main features are:
– Elevated creatinine kinase
– Hyperthermia and tachycardia
– Altered mental state
– Increased white cell count
– Insidious onset over 1-3 days
– Extrapyramidal dysfunction (muscle rigidity, tremor, dystonia)
– Autonomic dysfunction (Labile blood pressure, sweating, salivation, urinary incontinence)

Management is supportive of ICU care, anticholinergic drugs, increasing dopaminergic activity with Amantadine, L-dopa, and dantrolene, and non- depolarising neuromuscular blockade drugs.

Since Olanzapine is a potential cause of NMS it is not a treatment.

The temperature above which a gas cannot be liquefied no matter how much pressure is applied is its critical temperature. The critical temperature of nitrous oxide is 36.5°C

The minimum pressure that causes liquefaction is the critical pressure of that gas.

The Poynting effect refers to the phenomenon where mixing of liquid nitrous oxide at low pressure with oxygen at high pressure (in Entonox) leads to formation of gas of nitrous oxide.

There is no relevance of molecular weight to this question. it does not change with phase of a substance.

According to European Group protocol for the investigation of MH susceptibility, muscle biopsy should be performed on quadriceps muscle (either vastus medialis or vastus lateralis), using regional anaesthesia (avoiding local anaesthetic infiltration) or general anaesthetic techniques. Local anaesthetic solution within muscle fibres may affect in vitro contraction testing.

Desflurane is a weak triggering anaesthetic of malignant hyperthermia so is avoided in MH susceptible patients. This includes all volatile inhalational agents and suxamethonium.

General anaesthetic with the volatile free anaesthetic machine may be considered but spinal anaesthesia is a better choice due to the possibility of airway problems.

Tests are used to confirm the presence of a particular disease. However the results can be misleading at times since most of the tests have some limitations associated with them.
Sensitivity is the correct term that refers to the probability of a positive test. The others are explained below:

False Positive rates refer to the proportion of the patients who don’t have the condition being detected as positive.

False Negative rates refer to the proportion of the patients who have the condition being detected as negative (like the 20% of the patients that went undetected by the Ca-125 test).

Specificity describes the ability of a test to detect and pick up people without the disease. Absolute risk ratio compares the rate of two separate outcomes.

Codeine is easily absorbed from the gastrointestinal tract and converted to morphine and norcodeine in the liver via O- and N-demethylation. Morphine and norcodeine are excreted almost entirely by the kidney, primarily as conjugates with glucuronic acid.

By glucuronidation, phase II metabolism enzyme UDP-glucuronosyl transferase-2B7 converts morphine to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) (UGT2B7).

Approximately 60% of morphine is converted to M3G, with the remaining 6-10% converted to M6G. M3G is inactive, but M6G is said to be 4 to 650 times more potent on the MOP receptor than morphine.

When codeine is consumed, cytochrome P450 2D6 in the liver converts it to morphine (CYP2D6).

Some people have DNA variations that increase the activity of this enzyme, causing codeine to be converted to morphine more quickly and completely than in others. After taking codeine, these ultra-rapid metabolisers are more likely to have higher than normal levels of morphine in their blood.

Respiratory depression/obstruction can be caused by high levels of morphine and M6G, especially in people who have a history of obstructive sleep apnoea. The estimated number of ultra-rapid metabolisers ranges from 1 to 7 per 100 people, but some ethnic groups may have as many as 28 per 100 people.

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

A peripherally inserted central catheter (PICC) line is a long, thin tube inserted into the vein of a patient’s arm to gain access to the large central veins near the heart. PICC line is indicated for parenteral nutrition or to deliver medications. They can be used for medium-term venous access, defined as anywhere between several weeks to 6 months.

The veins of choice for PICC are:
1. Basilic
2. Brachial
3. Cephalic
4. Medial cubital vein

The vein of choice is the right basilic vein as it has a large circumference and is located superficially. It has the most straight route to the final destination of PICC (SVC or Right atrium). It courses through the axillary vein, then the subclavian, and finally settles into the SVC. It also has the least number of valves and a shallow angle of insertion when compared to the other veins.

The basilic vein drains the medial end of the dorsal arch of the upper limb, passes along the medial aspect of the forearm, and pierces the deep fascia at the elbow. The basilic vein joins the venae comitantes of the brachial artery to form the axillary vein at the elbow.
The posterior circumflex humeral vein is encountered before the axillary vein. However, a PICC line is unlikely to enter this structure because of its entry angle into the basilic vein.

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.

A tonsillar sinus or fossa is a space that is bordered by the triangular fold of the palatoglossal and palatopharyngeal arches in the lateral wall of the oral cavity. The palatine tonsils are in these sinuses.

The glossopharyngeal nerve is the main sensory nerve for the tonsillar fossa. The tonsillar branches of the glossopharyngeal nerve supply the palatine tonsils forming a plexus around it. Filaments from this plexus are distributed to the soft palate and fauces where they communicate with the palatine nerves. A lesser contribution is made by the lesser palatine nerve. Because of this otalgia may occur following tonsillectomy.

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

Medical gas cylinders are made up of molybdenum steel but not cast iron. They are checked and assessed at a regular interval.

At least one cylinder in each hundred are tested for tensile, pressure, smash, twist and straightening.

Nitrous Oxide cylinders contain a mixture of liquid and vapour at a pressure of approx. 4500 kPa or 45 Bar. Carbon dioxide cylinder contain gas at the pressure of 5000kPa.

The filling ratio is the ratio of mass of liquified gas in the cylinder to the mass of water required to fill the cylinder at the temperature of 15ºC. In the united kingdom, filling ratio of liquid nitrous oxide is 0.75. The cylinders are usually attached to the anaesthetic machine. As nitrous oxide is an N-methyl-d-aspartate receptor antagonist that may reduce the incidence of chronic post-surgical pain.

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.

Once the decision to deliver a baby by caesarean section has been made, it should be carried out with a level of urgency commensurate with the baby’s risk and the mother’s safety.

There are four types of caesarean section urgency:

Category 1: A threat to the life of the mother or the foetus. 30 minutes to make a delivery decision
Category 2 : Maternal or foetal compromise that is not immediately life threatening. In most cases, the decision to deliver is made within 75 minutes.
Category 3 – Early delivery is required, but there is no risk to the mother or the foetus.
Category 4: Elective delivery at a time that is convenient for both the mother and the maternity staff.

There may be evidence of foetal compromise in the example above (late foetal pulse decelerations and a borderline pH).

Blood samples from the foetus:
normal: 7.25 or above
borderline: 7.21 to 7.24
abnormal: 7.20 or below

When a foetal deceleration occurs, the mother should be given oxygen, kept in a left lateral position, and given a tocolytic if the foetal deceleration is hyper stimulating. Maintaining adequate hydration will reduce the likelihood of a caesarean section.

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

Because the patient has mild systemic disease, he is ASA 2 and the procedure will be performed under local anaesthesia.

The following factors should be considered when requesting preoperative investigations:

Indications derived from a preliminary clinical examination
Whether or not a general anaesthetic will be used, the possibility of asymptomatic abnormalities, and the scope of the surgery.

No special investigations are needed if the patient has no history of significant systemic disease and no abnormal findings on examination during the nurse-led assessment.

Functional residual capacity (FRC) is 1.7 to 3.5L/kg

A capacity is the sum of two or more volumes. The total lung capacity (TLC) is total sum of the volume of gas present in all lung compartments upon maximum inspiration. It is represented mathematically as:

Total lung capacity (TLC) = Vital capacity (VC) + Residual volume (RV)

The residual volume (RV) is the volume of gas still present within the lung post maximum exhalation. It cannot be measured by spirometry, but can be using a body plethysmograph and also with the helium dilution technique.

Closing capacity (CC) is the volume of gas within the lungs at which small airways close upon expiration. It increases with age and is especially important when it surpasses the FRC as it causes changes in ventilation/perfusion mismatch and hypoxia.
In the supine position, a patient with a normal body mass index and no history of lung pathology, the CC equals the FRC at approximately 44, and at approximately 66 at standing position.

Atrial natriuretic peptide (ANP) is secreted mainly from myocytes of right atrium and ventricle in response to increased blood volume.
It is secreted by both the right and left atria (right >> left).

It is a 28 amino acid peptide hormone, which acts via cGMP
degraded by endopeptidases.

It serves to promote the excretion of sodium, lowers blood pressure, and antagonise the actions of angiotensin II and aldosterone.

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

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

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

Numerous signalling pathways appear to be involved in transporter regulation.

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

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

Adenosine is the first line for AV nodal re-entry tachycardia. An initial dose of 6 mg is given, and a consequent second dose or third dose of 12 mg is administered if the initial dose fails to terminate the arrhythmia.

Aside from Adenosine, a vagal manoeuvre (e.g. carotid massage) is done to help terminate the supraventricular arrhythmia.

Amiodarone is not a first-line drug for supraventricular tachycardias. Digoxin and Propranolol can be considered if the arrhythmia is of a narrow complex irregular type. Verapamil is an alternative to Adenosine if the latter is contraindicated.

Oxygen is formed by a molecule of oxygen and two molecules of hydrogen with a molecular formula of H2O

The critical temperature is defined as a temperature above which the substance cannot be liquefied, no matter how much pressure is applied.
Water has a critical temperature of -118.6oC. So, it cannot be liquified at room temperature.

Medical oxygen cylinder is stored in a cylinder with a white shoulder and black body. Meanwhile, medial air is stored in cylinders with a white and black shoulder and a French grey body.

The partial pressure of air at a high altitude is less but the relative concentration remains constant.

Dinamap continuously measures the systolic, diastolic and mean arterial pressure along with pulse rate, thereby providing a continuous monitoring of the blood pressure using the osscillitonometric principle of measurement.

The device loses accuracy towards the extremes of BP and is more accurate with systolic compared with diastolic pressure. In arrhythmias such as AF, the devices are also inaccurate due to the major fluctuations associated with the individual pulse pressure variations.

The manual BP device is still the gold standard for BP measurement and monitoring.

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

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

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

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

Recall bias introduced when participants in a study are systematically more or less likely to recall and relate information on exposure depending on their outcome status.

In procedure bias, the researcher decides assignment of a treatment versus control and assigns particular patients to one group or the other non-randomly. This is unlikely to have occurred in this case, although it is not mentioned specifically.

Self Selection or volunteer bias occur when those subjects are selected to participate in the study who are not the representative of the entire target population. those subjects may be from high socio-economic status and practice those activities or lifestyle that improves their health.

Lead-time bias occurs when a disease is detected by a screening test at an earlier time point rather than it would have been diagnosed by its clinical appearance. In this bias, earlier detection improves the survival time in the intervention group.

Prostacyclin is a strong vasodilator. It is administered as an intravenous infusion for critical ischemia. Commercially, it is available as sodium epoprodtenol.

Atrial Natriuretic peptide (ANP) hormone secreted from the atria, kidney, and neural tissues. It primarily acts on renal vessel to maintain normal blood pressure and reduce plasma volume by: increasing the renal excretion of salt and water, glomerular filtration rate, vasodilation, and by increasing the vascular permeability. It also inhibits the release of renin and aldosterone.

Indoramin is an alpha-adrenoceptor blocking agent. which act selectively on post-synaptic-alpha adrenoreceptor, leading to decease in peripheral resistance.

Angiotensin II is a vasoconstrictor, causing high sodium retention. It also increases the secretion of antidiuretic hormone (ADH) and aldosterone level.

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.

Hiatus is an opening in the diaphragm. A hiatal hernia is a protrusion of the upper part of the stomach through an opening in the diaphragm, the oesophageal hiatus, into the thorax. The oesophageal hiatus occurs at the level of T10 in the right crus of the diaphragm.

Other important openings in the diaphragm:
T8: vena cava, terminal branches of the right phrenic nerve
T10: oesophagus, vagal trunks, left anterior phrenic vessels, oesophageal branches of the left gastric vessels
T12: descending aorta, thoracic duct, azygous and hemi-azygous vein

An opening in the diaphragm is called a hiatus. The oesophageal hiatus is at vertebral level T10. A hiatus hernia is where the stomach bulges through the oesophageal hiatus hence the name – hiatus hernia.

Prerenal failure has a serum urea: creatinine ratio of >100, while acute kidney injury has a ratio of 40.
In prerenal failure, ADH levels are typically high, resulting in water, urea, and sodium resorption. The fractional sodium excretion is less than 1%, but it is greater than 2% in acute tubular necrosis.
Prerenal azotaemia has higher serum urea nitrogen/serum creatinine ratios (>20), whereas acute tubular necrosis has lower ratios (10-15). The normal range is between 12 and 20.
Urinary sodium is less than 20 in prerenal failure and greater than 40 in acute tubular necrosis.
Prerenal failure has a urine osmolality of >500, while acute tubular necrosis has an osmolality of 350.
Prerenal failure has a urine/serum creatinine ratio of >40, while acute tubular necrosis has a urine/serum creatinine ratio of 20.

The concentrations of serum urea or creatinine change in inverse proportion to glomerular filtration. Changes in serum creatinine concentrations are more reliable than changes in serum urea concentrations in predicting GFR. Creatinine is produced at a constant rate from creatine, and blood concentrations are almost entirely determined by GFR.

A number of factors influence urea formation, including liver function, protein intake, and protein catabolism rate. Urea excretion is also influenced by hydration status, the amount of water reabsorption, and GFR.

A high serum creatinine level, as well as a urine output of less than 10 mL/hour and the production of concentrated looking urine, do not necessarily indicate a specific cause of oliguria.

Randomisation can be used to provide control over the confounding variables during the design stage of a study however during analytical stage a technique called stratification is used for controlling confounding variables. Since the question asks for the information that is factually incorrect.

Creatinine clearance is a test used to approximate the glomerular filtration rate (GFR) as an assessment of kidney function.

Creatinine is formed during the breakdown of dietary sources of meat and skeletal muscle. It is secreted at a consistent concentration and pace into the body’s circulation, and is easily filtered across the glomerulus without being reabsorbed or metabolized by the kidney.

It is represented mathematically as:
Creatinine clearance (CL) = U x V/P
where,
U: Urinary creatinine concentration (mg/mL)
V: Volume of urine (mL/min)
P: Plasma creatinine concentration (mg/mL)

Therefore, in this case:
CL: 1.25 x 1 = 125mL/min
0.1

The inflow of blood from the superior vena cava is directed towards the right atrioventricular orifice. It returns deoxygenated blood from all structures superior to the diaphragm, except the lungs and heart.

There are no valves in the superior vena cava which is why it is relatively easy to insert a CVP line from the internal jugular vein into the right atrium. The brachiocephalic vein is similar as it also has no valves.

Oxygen consumption (VO2) refers to the optimal amount of oxygen used by the body during exercise.

It is calculated mathematically by:

VO2 = 3.5 x 50 x 8 = 1400 mL/kg/minute

where,

1 MET = 3.5 mL O2/kg/minute is utilized by the body.

Note:

1 MET Eating
Dressing
Use toilet
Walking slowly on level ground at 2-3 mph
2 METs Playing a musical instrument
Walking indoors around house
Light housework
4 METs Climbing a flight of stairs
Walking up hill
Running a short distance
Heavy housework, scrubbing floors, moving heavy furniture
Walking on level ground at 4 mph
Recreational activity, e.g. golf, bowling, dancing, tennis
6 METs Leisurely swimming
Leisurely cycling along the flat (8-10 mph)
8 METs Cycling along the flat (10-14 mph)
Basketball game
10 METs Moderate to hard swimming
Competitive football
Fast cycling (14-16 mph)

The upper limb venous drainage is divided into superficial and deep. The superficial veins are accessible to draw blood for investigations. The cephalic, basilic, and median cubital veins are superficial veins.

The median cubital vein connects the cephalic vein and basilic vein. It is located anteriorly in the antecubital fossa and is preferred for venepuncture due to its palpability and ease of access.

The basilic vein and cephalic vein are the primary veins that drain the upper limb. They begin as the dorsal venous arch. The basilic vein originates from the ulnar side, while the cephalic vein originates from the radial side of the dorsal arch of the upper limb.

Carbon dioxide (CO2), is a carbonic gas made up of two dissimilar atoms, namely one carbon atom and two oxygen atoms. Capnography is a technique used to measure carbon dioxide during a respiratory cycle, and it consists in calculating the concentration of the partial pressure of CO2, through the absorption of the infrared light, namely that CO2 absorbs infrared radiation at a wavelength of 4.28 µm.

End-tidal CO2 (ETCO2), referring to the level of the carbon dioxide released at the end of an exhaled breath, is required to be continuously monitored, especially in ventilated patients, as it is a sensitive and a non invasive technique that provides immediate information about ventilation, circulation, and metabolism functions. ETCO2 is normally lower than the arterial partial pressure and varies between 0.6 and 0.7 kPa.

There are two methods used to measure carbon dioxide. The sidestream capnometer method samples gases at a set flow rate (150-200 mL/min) from a sampling area through small diameter tubing, and the mainstream analyser method that uses a direct measurement of the patient exhaled CO2 by a relatively large and heavy sensors. Sidestram method allows the analysis of multiple gases and anaesthetic vapours comparing to the mainstream method that does not allow the measurement of other gases.

The most important determinant of preoxygenation adequacy is expired fraction of oxygen. Denitrogenating of the functional residual capacity is the purpose of preoxygenation. This is dependent on three vital factors: (1) respiratory rate; (2) inspired volume, and; (3) inspired oxygen concentration (FiO2).

Arterial oxygen saturation does not efficiently determine adequacy of preoxygenation because of its inability to measure tissue reserves. Arterial partial pressure of oxygen is also unsuitable for determining preoxygenation adequacy. Moreover, the absence of central cyanosis is a very crude sign of low tissue oxygenation.

Selection bias is when randomisation is not achieved and is often a result of in efficient recruiting method.

Recall bias is specifically appropriate to the case control studies that is when ever the memories retrieved by the participants differ in accuracy.

Measurement bias can be characterized by gathering of information in a manner that is distorted.

When the participants of a research study are recruited from the hospitals rather than the general population, its called Berkson Bias.

Confounding bias is the major player here because in this case the effects of smoking can be masked behind and can be read as outcomes of lower socio economic status. This extraneous factor (Smoking), distorts the founding.

The umbilical vein closes once the umbilical cord is clamped following birth. This causes a rise in systemic vascular resistance, closing the ductus venosus.

Upon birth, the pulmonary vascular resistance is decreased as the lungs are aerated.

At birth, there is a rise in oxygen tension which causes the corresponding constriction of the ductus arteriosus. This prevents a left to right shunt as it stops aortic blood and blood from the pulmonary artery from mixing. The ventricles do no have an opening connecting them.

The foramen ovale closes soon after birth. It is the septum opening between the left and right atrium.

An adult’s cardiac output is expected to be 5 L/min

The occlusion of the left anterior descending (LAD) coronary artery causes anterior ST elevation myocardial infarction (STEMI). It has the worst prognosis of all the infarct locations due to its larger infarct size. It has a higher rate of total mortality (27 percent versus 11 percent), heart failure (41 percent versus 15 percent), and a lower ejection fraction on admission than an inferior myocardial infarction (38 percent versus 55 percent ).

The LAD artery supplies the majority of the interventricular septum, as well as the anterior, lateral, and apical walls of the left ventricle, as well as the majority of the right and left bundle branches and the bicuspid valve’s anterior papillary muscle (left ventricle).

The left or right ventricle’s end-diastolic volume (EDV) is the volume of blood in each chamber at the end of diastole before systole. Preload is synonymous with the EDV.

120 mL is a typical left ventricular EDV (range 65-240 mL). The EDV of the right ventricle in a typical range is (100-160 mL).

With an ejection fraction (EF) of less than 45 percent, the patient is most likely suffering from systolic dysfunction. Increases in right and left ventricular end-diastolic pressures and volumes are likely with a reduced EF because the ventricles are not adequately emptied. The left atrium and the pulmonary vasculature are affected by the increased pressures on the left side of the heart.

By causing an imbalance of the Starling forces acting across the capillaries, increased hydrostatic pressure in the pulmonary circulation favours the development of pulmonary oedema. With cardiogenic pulmonary oedema, capillary permeability is likely to remain unchanged.

Biventricular failure will result as a result of the pressure changes being transmitted to the right side of the circulation. The patient’s systemic vascular resistance is likely to be elevated as well, but it is not the most likely cause of his symptoms. The patient is suffering from cardiogenic shock as a result of biventricular failure. The patient has low cardiac output and is hypotensive. Right ventricular filling pressures are elevated, indicating right ventricular dysfunction.

The Glasgow Coma Scale (GCS) has been used in outcome models as a measure of physiological derangement and as a tool for assessing head trauma.

Eye opening (E):

4 Spontaneously
3 Responds to voice
2 Responds to painful stimulus
1 No response.

Best verbal response (V):

5 Orientated, converses normally
4 Confused, disoriented conversation, but able to answer basic questions
3 Inappropriate responses, words discernible
2 Incomprehensible speech
1 Makes no sounds.

Best motor response (M):

6 Obeys commands for movement
5 Purposeful movement to painful stimulus
4 Withdraws from pain
3 Abnormal (spastic) flexor response to painful stimuli, decorticate posture
2 Extensor response to painful stimuli, decerebrate posture
1 No response.

In this case, GCS = 2+3+5 = 10.

Adrenaline acts on ?1, ?2,?1, and ?2 receptors and also on dopamine receptors (D1, D2) and have sympathomimetic effects.

Natural catecholamines are Adrenaline, Noradrenaline, and Dopamine

Adrenaline is a sympathomimetic amine with both alpha and beta-adrenergic stimulating properties.
Adrenaline is the drug of choice for anaphylactic shock
Adrenaline is also used in patients with cardiac arrest. The preferred route is i.v. followed by the intra-osseous and endotracheal route.

Adrenaline is released by the adrenal glands, acts on ? 1 and 2, ? 1 and 2 receptors, and is responsible for fight or flight response.

It acts on ? 2 receptors in skeletal muscle vessels-causing vasodilation.

It acts on ? adrenergic receptors to inhibit insulin secretion by the pancreas. It also stimulates glycogenolysis in the liver and muscle, stimulates glycolysis in muscle.

It acts on ? adrenergic receptors to stimulate glucagon secretion in the pancreas
It also stimulates Adrenocorticotrophic Hormone (ACTH) and stimulates lipolysis by adipose tissue

Vecuronium is used as a part of general anaesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation. It is a monoquaternary aminosteroid (not quaternary) non- depolarising neuromuscular blocking drug.

It has a structure similar to both rocuronium and pancuronium. The only difference is the substitution of specific groups on the steroid structure.

Vecuronium is not associated with the release of norepinephrine from sympathetic nerve endings. However, Pancuronium has norepinephrine releasing the property.

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

Phase 0 trials assist the scientists in studying the behaviour of drugs in humans by micro dosing patients. They are used to speed up the developmental process. They have no measurable therapeutic effect and efficiency.

The Number Needed to Treat (NNT) is the number of patients you need to treat to prevent one additional bad outcome. For example, if a drug has an NNT of 5, it means you have to treat 5 people with the drug to prevent one additional bad outcome.

To calculate the NNT, you need to know the Absolute Risk Reduction (ARR); the NNT is the inverse of the ARR:

NNT = 1/ARR

Where ARR = CER (Control Event Rate) – EER (Experimental Event Rate).

NNTs are always rounded up to the nearest whole number.

In this case, the NNT can be computed as follows:

ARR = 10% – 5% = 0.05

NNT = 1/0.05 = 20

Correctly used, antibiotic prophylaxis can reduce
the total use of antibiotics.
There is strong scientific support that antibiotic
prophylaxis reduces the development of infection after:

• Operations and endoscopic procedures in the large intestine,
  the rectum, and the stomach (including appendectomies and
  penetrating abdominal trauma), and after percutaneous endoscopic gastrostomy (PEG)
• Cardiovascular surgery, and insertion of pacemakers
• Breast cancer surgery
• Hysterectomy
• Reduction of simple fractures and prosthetic limb surgery
• Complicated surgery for cancer in the ear, nose, and throat
  regions
• Transrectal biopsy and resection of the prostate (febrile urinary
  tract infection and blood poisoning).

In most cases the scientific evidence is inadequate to determine
which type of antibiotic is most effective for antibiotic prophylaxis.

Sugammadex is a modified cyclodextrin that works as an aminosteroid neuromuscular blocking (nmb) reversal agent. By encapsulating each molecule in the plasma, it rapidly reverses rocuronium and, to a lesser extent, vecuronium-induced neuromuscular blockade. Consequently, a  concentration gradient favours the movement of these nmb agents away from the neuromuscular junction.  Pancuronium-induced neuromuscular blockade at low levels has also been reversed.

By inhibiting voltage-dependent calcium channels at the neuromuscular junction, antibiotics in the aminoglycoside group potentiate neuromuscular blocking agents. This can be reversed by giving calcium but not neostigmine or sugammadex.

Sugammadex will not reverse the effects of mivacurium, which belongs to the benzylisoquinolinium class of drugs.

A phase II or desensitisation block occurs when the motor end-plate becomes less sensitive to acetylcholine as a result of an overdose or repeated administration of suxamethonium. The use of neostigmine has been shown to be effective in reversing this weakness.

The mitral valve is the valve between the left atrium and left ventricle. It opens when the heart is in diastole (relaxation) which allows blood to flow from the left atrium to the left ventricle. In systole (contraction), the mitral valve closes to prevent the backflow of blood from the left ventricle to the left atrium.

The mitral valve is located posterior to the sternum at the level of the 4th costal cartilage. It is best auscultated over the cardiac apex, where its closure marks the first heart sound.

The mitral valve anatomy is composed of five main structures:
1. Left atrial wall – the myocardium of the left atrial wall extends over the posterior leaflet of the mitral valve. (left atrial enlargement is one of the causes for mitral regurgitation)
2. Mitral annulus – a fibrous ring that connects with the anterior and posterior leaflets. It functions as a sphincter that contracts and reduces the surface area of the valve during systole (Annular dilatation can also lead to mitral regurgitation)
3. Mitral valve leaflets (cusps) – The mitral valve is the only valve in the heart with two cusps or leaflets. One anterior and one posterior.
i. The anterior leaflet is located posterior to the aortic root and is also anchored to the aortic root.
ii. The posterior leaflet is located posterior to the two commissural areas.
4. Chordae tendinae – The chordae tendinae connects both the cusps to the papillary muscles.
5. Papillary muscles – These muscles and their cords support the mitral valve, allowing the cusps to resist the pressure developed during contractions (pumping) of the left ventricle

The anterior and posterior cusps are attached to the chordae tendinae which itself is attached to the left ventricle via papillary muscle.

An echocardiogram provides real-time visualisation of cardiac structures. The ejection fraction (EF) is normally measured using this system.

The ejection fraction (EF) can be deduced mathematically if the patient’s end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV) are known, as:

SV = EDV – ESV, and

EF = SV/EDV x 100

The normal range for EF is >55-70%.

For this patient,

SV= 40 – 30 = 10 mL, therefore

EF = 10/40 x 100 = 25%

Alfentanil is less lipid-soluble than fentanyl and thus is less permeable to the membrane making it less potent.

Alfentanil is a phenylpiperidine opioid analgesic with rapid onset and shorter duration of action.

Alfentanil has less volume of distribution due to its high plasma protein binding (92%)

It can cause respiratory depression and can cause sedation

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.

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 total body water content of a 70kg man is (70 × 0.6) = 42 litres. For a woman, the calculation is (70 × 0.55) = 38.5 litres.

For a man, it is subdivided into:

Extracellular fluid (ECF) = 14L (1/3)
Intracellular fluid (ICF) = 28L (2/3).

The ECF volume is further divided into:

Interstitial fluid = 10.5 litres
Plasma = 3 litres
Transcellular fluid (CSF/synovial fluid) = 0.5 litres.

Directly measured fluid compartments:

Heavy water (deuterium) can be used to measure total body water content, which is freely distributed.
Albumin labelled with a radioactive isotope or using a dye called Evans blue can be used to measure Plasma volume . They do not diffuse into red blood cells.
Radiolabelled (Cr-51) red blood cells can be used to measure total erythrocyte volume.
Inulin as the tracer can be used to measure ECF volume as it circulate freely in the interstitial and plasma volumes.

Indirectly measured fluid compartments:

Total blood volume can be calculated with the level of haematocrit and the volume of total circulating red blood cells.
ICF volume can be calculated by subtracting ECF volume from total blood volume.

The coronary sinus is large venous structure located on the posterior aspect of the left atrium, coursing within the left atrioventricular groove. The function of the coronary sinus is to drain the venous blood from the majority of the heart. It opens into the right atrium between the opening of inferior vena cava, the fossa ovalis and the right atrioventricular orifice. The coronary sinus is often guarded by a thin, semicircular endocardial fold, also known as the thebesian valve.
Tributaries include: Great cardiac vein, middle cardiac vein, small cardiac vein, posterior vein of left ventricle, oblique vein of left atrium. The great cardiac vein is the largest tributary of the coronary sinus.

Respiratory inspiration causes a decreased pressure in the thoracic cavity, which in turn causes more blood to flow into the atrium.

Sitting up decreases venous because of the action of gravity on blood in the venous system.
Hypotension also decreases venous return.
A less compliant aorta, like in aortic stenosis increases end systolic left ventricular volume which decreases stroke volume.

Systemic vascular resistance = mean arterial pressure / cardiac output. Increased vascular resistance impedes the flow of blood back to the heart.

Increased venous return increases end diastolic LV volume as there is more blood returning to the ventricles.

The Delphi is a group facilitation technique that seeks to obtain consensus on the opinions of `experts’ through a series of structured questionnaires (commonly referred to as rounds). By using successive questionnaires, opinions are considered in a non-adversarial manner, with the current status of the groups’ collective opinion being repeatedly fed back. Studies employing the Delphi make use of individuals who have knowledge of the topic being investigated

Cardiopulmonary exercise testing (CPX, CPEX, CPET) is a non-invasive testing method used to determine the performance of the heart, lungs and skeletal muscle. It measures the exercise tolerance of the patient.

The parameters measured include:

ECG and ST-segment analysis and blood pressure
Oxygen consumption (VO2)
Carbon dioxide production (VCO2)
Gas flows and volumes
Respiratory exchange ratio (RER)
Respiratory rate
Anaerobic threshold (AT)

The anaerobic threshold (AT) is an estimate of exercise ability. Any measurement below 11 ml/kg/min is usually related with an increase in mortality, especially when there is a background of myocardial ischaemia occurring during the test.

Peak VO2 <20 mL/kg with a low AT have a correlation with postoperative complications and a 30 day mortality. The CPX test is used for risk-testing patients prior to surgery to determine the appropriate postoperative care facilities. The V slope measured in CPX testing represents VO2 versus VCO2 relationship. During AT, the ramp of V slope increases, but does not provide a picture of postoperative mortality.

The correct answer is the clotting cascade, which occurs via a positive feedback mechanism. As clotting factors are attracted to a site, their presence attracts further clotting factors. This continues until a functioning clot is formed.

This patient has presented with symptoms of hypothyroidism and symptoms include weight gain, lethargy, cold intolerance, dry skin, coarse hair and constipation. It can be treated by replacing the missing thyroid hormone with levothyroxine which is a synthetic version of thyroxine (T4).

Serum carbon dioxide (CO2) is controlled via a negative feedback mechanism as well. Chemoreceptors can detect when the serum CO2 is high, and send an impulse to the respiratory centre of the brain to increase the respiratory rate. As a result, more CO2 is exhaled which lowers the serum concentration.

Cortisol is also released according to a negative feedback mechanism. Cortisol acts on both the hypothalamus and the anterior pituitary. Its action serve to decrease the formation of corticotrophin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), respectively. CRH acts on the anterior pituitary to release ACTH. This then acts on the adrenal gland to cause the release of cortisol. Thus, inhibition of CRH and ACTH formation results in high levels of cortisol which inhibit its further release.

Blood pressure (BP) is controlled via a negative feedback mechanism. Low BP results in renin-angiotensin-aldosterone system (RAAS) activation. This leads to vasoconstriction and retention of salt and water which increased BP.
Blood sugar is controlled via a negative feedback mechanism. A rise in blood sugar causes insulin to be released. Insulin acts to transport glucose into the cell which lowers blood sugar.

There are different types of temperature measurement. These include:

Thermistor – this is a type of semiconductor, meaning they have greater resistance than conducting materials, but lower resistance than insulating materials. There are small beads of semiconductor material (e.g. metal oxide) which are incorporated into a Wheatstone bridge circuit. As the temperature increases, the resistance of the bead decreases exponentially

Thermocouple – Two different metals make up a thermocouple. Generally, in the form of two wires twisted, welded, or crimped together. Temperature is sensed by measuring the voltage. A potential difference is created that is proportional to the temperature at the junction (Seebeck effect)

Platinum resistance thermometers (PTR) – uses platinum for determining the temperature. The principle used is that the resistance of platinum changes with the change of temperature. The thermometer measures the temperature over the range of 200°C to1200°C. Resistance in metals show a linear increase with temperature

Tympanic thermometers – uses infrared radiation which is emitted by all living beings. It analyses the intensity and wavelength and then transduces the heat energy into a measurable electrical output

Gauge/dial thermometers – Uses coils of different metals with different co-efficient of expansion. These either tighten or relax with changes in temperature, moving a lever on a calibrated dial.

There are different types of temperature measurement. These include:

Thermistor – this is a type of semiconductor, meaning they have greater resistance than conducting materials, but lower resistance than insulating materials. There are small beads of semiconductor material (e.g. metal oxide) which are incorporated into a Wheatstone bridge circuit. As the temperature increases, the resistance of the bead decreases exponentially

Thermocouple – Two different metals make up a thermocouple. Generally, in the form of two wires twisted, welded, or crimped together. Temperature is sensed by measuring the voltage. A potential difference is created that is proportional to the temperature at the junction (Seebeck effect)

Platinum resistance thermometers (PTR) – uses platinum for determining the temperature. The principle used is that the resistance of platinum changes with the change of temperature. The thermometer measures the temperature over the range of 200°C to1200°C. Resistance in metals show a linear increase with temperature

Tympanic thermometers – uses infrared radiation which is emitted by all living beings. It analyses the intensity and wavelength and then transduces the heat energy into a measurable electrical output

Gauge/dial thermometers – Uses coils of different metals with different co-efficient of expansion. These either tighten or relax with changes in temperature, moving a lever on a calibrated dial.

The deep inguinal ring lies approximately 1.5-2cm above the midpoint of the inguinal ligament, the halfway point between the anterior superior iliac spine and the pubic tubercle, next to the epigastric vessels.

It is an important point in determining the nature of an inguinal hernia (direct or indirect). The patient is asked to cough after the hernia is reduced, with pressure applied to the deep inguinal ring. The hernia reappearing indicates it is direct, moving through the posterior wall of the inguinal canal.

Inferior and lateral to the pubic tubercle is the normal anatomical position of the neck of a femoral hernia.

Superior and medial to the pubic tubercle is the site of the superficial inguinal ring, and the normal anatomical position of the neck of an inguinal hernia.

The mid-inguinal point is located halways between the pubic symphysis and the anterior superior iliac spine. It is the surface marking for taking the femoral pulse.

There are four parathyroid glands that lie on the medial half of the posterior surface of each lobe of the thyroid gland, inside its sheath. There are two superior and two inferior parathyroid glands.

The common carotid artery is a lateral relation of the inferior parathyroid.

Staphylococcus aureus infection is the most likely cause.

Surgical site infections (SSI) occur when there is a breach in tissue surfaces and allow normal commensals and other pathogens to initiate infection. They are a major cause of morbidity and mortality.

SSI comprise up to 20% of healthcare associated infections and approximately 5% of patients undergoing surgery will develop an SSI as a result.
The organisms are usually derived from the patient’s own body.

Measures that may increase the risk of SSI include:
-Shaving the wound using a single use electrical razor with a disposable head
-Using a non iodine impregnated surgical drape if one is needed
-Tissue hypoxia
-Delayed prophylactic antibiotics administration in tourniquet surgery, patients with a prosthesis or valve, in clean-contaminated surgery of in contaminated surgery.

Measures that may decrease the risk of SSI include:
1. Intraoperatively
– Prepare the skin with alcoholic chlorhexidine (Lowest incidence of SSI)
-Cover surgical site with dressing

In contrast to previous individual RCT’s, a recent meta analysis has confirmed that administration of supplementary oxygen does not reduce the risk of wound infection and wound edge protectors do not appear to confer benefit.

2. Post operatively
Tissue viability advice for management of surgical wounds healing by secondary intention

Use of diathermy for skin incisions
In the NICE guidelines the use of diathermy for skin incisions is not advocated. Several randomised controlled trials have been undertaken and demonstrated no increase in risk of SSI when diathermy is used.

Staphylococcus aureus colonizes the nasopharynx in >20% of the general population.

Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to flucloxacillin.

Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF). THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis.

All ?-lactam antibiotics like penicillin interfere with the synthesis of the bacterial cell walls. The ?-lactam antibiotics inhibit the transpeptidases so that cross-linking (which maintains the close-knit structure of the cell wall) does not take place

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.

Since the data is normally distributed, 95.4% of the values lie with in 2 standard deviations from mean. The rest of the 4.6% are distributed symmetrically outside of that range which means 2.3% of the values lie above 2 standard deviations of the mean.

Risk ratio (relative risk) compares the probability of an event in an exposed (experimental) group to that of an event in the unexposed (control) group.

A relative risk of 1 suggests that there is no discernible difference in the outcome whether or not it has been exposed.

A relative risk of less than 1 indicates that probability of occurrence of an event is less if there is exposure.

A relative risk of greater than 1 highlights that an event is most likely to occur if it was provided exposure. Since you believe that exposure (the new drug) would have side effects, the value should be greater than 1.

Closing capacity refers to volume of gas within the lungs at which the conducting small airways begin to close, that is, the point during expiration when small airways close.

It is calculated mathematically as:

Closing capacity = Closing volume (CV) + Residual volume (RV)

Functional residual capacity (FRC) is the volume of gas still present within the lungs post expiration.

Closing capacity is lower than the functional residual capacity in younger adults, but begins to rise to eventually equal, and then exceed it with increasing age (at about middle age), increasing intrabdominal pressure, decreasing blood flow in the pulmonary system and parenchymal disease within the pulmonary system.

The external carotid artery has eight important branches:
1. Superior thyroid artery
2. Ascending pharyngeal artery
3. Lingual artery
4. Facial artery
5. Occipital artery
6. Posterior auricular artery
7. Maxillary artery (terminal branch)
8. Superficial temporal artery (terminal branch)

There is no mandibular artery but the first part of the maxillary artery is called the mandibular part as it is posterior to the lateral pterygoid muscle.
The maxillary artery is divided into three portions by its relation to the lateral pterygoid muscle:
first (mandibular) part: posterior to the lateral pterygoid muscle
second (pterygoid or muscular) part: within the lateral pterygoid muscle
third (pterygopalatine) part: anterior to the lateral pterygoid muscle

The level of statistical significance required influences the sample size used. This is because sample size is used in the calculation of SD/SE.

Sample size does not affect

The level of acceptance
The alternative hypothesis with a general level set at p<0.05
The test to be used.

Experience of the investigator and the type of patient recruited should have no bearing on the required sample size.

The structures in the porta hepatis from anterior to posterior are:

The ducts: Most anterior are the left and right hepatic ducts.

The arteries: Next are the left and right hepatic arteries

The veins: Next is the portal vein

The epiploic foramen of Winslow lies most posterior at the porta hepatis.

The first line of treatment in case of hypotension is fluid resuscitation.

Activated charcoal can be used within one hour of tricyclic antidepressant ingestion but an intact and secure airway must be checked before intervention. The risk of aspiration should be assessed.

Vasopressors are indicated for the treatment of hypotension following (Tricyclic Antidepressant) TCA overdose when patients fail to respond to fluids and bicarbonate.

Dose response curves are plotted as % response to drug against Logarithm of drug concentration. The graph is usually sigmoid shaped.

Any drug that has high affinity and high intrinsic activity is likely an agonist. A drug with high affinity but no intrinsic activity will act as an antagonist. Displacement of an agonist also depends on the relative concentrations of the two drugs at the receptor sites.

Maximal response may be achieved by activation of a small proportion of receptor sites.

The diaphragm divides the thoracic cavity from the abdominal cavity. Structures penetrate the diaphragm at different vertebral levels through openings in the diaphragm to communicate between the two cavities. The diaphragm has openings at three vertebral levels:

T8: vena cava, terminal branches of the right phrenic nerve
T10: oesophagus, vagal trunks, left anterior phrenic vessels, oesophageal branches of the left gastric vessels
T12: descending aorta, thoracic duct, azygous and hemi-azygous vein

Eye damage is the most common potential hazard associated with laser energy. Everyone in the laser treatment room has the risk of eye exposure when working with a Class 3b or Class 4 healthcare laser system, and damage to various structures in the eye depending on wavelength of the laser if they are unprotected.

Red and near-infrared light (400-1400 nm) has very high penetration power. The light causes painless burns on the retina after it is absorbed by melanin in the pigment epithelium just behind the photoreceptors.

Infrared radiation (IR), or infrared light (>1060 nm), is a type of radiant energy that’s invisible to human eyes and hence won’t elicit the protective blink.

Ultraviolet light (<400 nm) is also a form of electromagnetic radiation which is can penetrate the cornea and be absorbed by the iris or the pupil and cause burn injuries or cataract occur due to irreversible photochemical retinal damage. Safety eyewear is the best method of providing eye protection and are designed to absorb light specific to the laser being used. Laser protective eyewear (LPE) includes glasses or goggles of proper optical density (OD). The lenses should not be glass or plastic. The LPE should withstand direct and diffuse scattered laser beams. The laser protection supervisor (LPS) or LSO is an individual who is responsible for any clinical area in which lasers are used. They are expected to have a certain level of equipment and determine what control measures are appropriate, for each individual system, but their presence does not guarantee the chances of having an eye injury. Class 1 lasers are generally safe under every conceivable condition and is not likely to cause any eye damage. Class 3b or Class 4 medical laser systems are utilized in healthcare which have their own safety precautions. Polarized spectacles can make your eyes more comfortable by eliminated glare, however, they will not be able to offer any protection against wavelengths at which laser act.
Using short bursts to reduce energy is also not correct as it would still be harmful to eye.

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

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

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

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

Attributable proportion is the proportion of disease that is caused due to exposure. It refers to the proportion of disease that would be eradicated from a particular population if the disease rate was diminished to match that of the unexposed group.

Risk ratio (relative risk) compares the probability of an event in an exposed (experimental) group to that of an event in the unexposed (control) group. Thus two are not the same.

The attributable risk is the rate of a disease in an exposed group to that of a group that has not been exposed to it i.e. how many deaths did the exposure cause.

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.

A higher frequency ultrasound comes with a better resolution of the digital image. Ultrasound with a frequency of 15 MHz is best used in imaging of superficial organs such as the thyroid gland, muscles, tendons and breasts whereas deep organs are better imaged using a lower frequency of 2-7MHz because of its ability for deeper penetration but lower resolution. These low frequency probes are also used to diagnose ascites, pleural effusions or can be used in echocardiography.

The US probe emits and then absorbs a reflected wave. Similar to brightness control, increasing the gain will amplify the return signal which is then attenuated by the tissue. This increases the signal to noise ratio.
A high frame rate, which basically means the number of times an image is updated onto the screen per second, improves the resolution of a moving 3D image which has become more accurate as the computing power has increased.

Widening of the image field can be obtained by altering the penetration depth which is obtained by changing the frequency of the US beam

The correlation coefficient gives us the idea about relation between two parameters. i.e. to what extent change in parameter A could prompt a change in parameter B. The numerical value of correlation coefficient could not be greater than 1.

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.

The usual method of calculating the dose of a drug to be given to patients of normal weight is to use total body weight (TBW). This is because the lean body weight (LBW) and ideal body weight (IBW) dosing scalars are similar in these patients.

Because the LBW and fat mass do not increase in proportion in patients with morbid obesity, this is not the case. Drugs that are lipid soluble, such as propofol or thiopentone, can cause a relative overdose. Lean body mass is a better scalar in these situations.

Suxamethonium has a small volume of distribution, so the dose is best calculated using the TBW to ensure optimal and deep intubating conditions. The higher dose was justified because these patients’ plasma cholinesterase activity was elevated.

Other scalars include:

The dose of highly lipid soluble drugs like benzodiazepines, thiopentone, and propofol can be calculated using lean body weight (LBW). The formula LBW = IBW + 20% can be used on occasion.

Fentanyl, rocuronium, atracurium, vecuronium, morphine, paracetamol, bupivacaine, and lidocaine are all administered with LBW.

Formulas can be used to calculate the ideal body weight (IBW). There are a number of drawbacks, including the fact that patients of the same height receive the same dose, and the formulae do not account for changes in body composition associated with obesity. Because IBW is typically lower than LBW, administering a drug based on IBW may result in underdosing. The body mass index (BMI) isn’t used to calculate drug dosage directly.

Only 1 percent of the calcium in the human body is found in the plasma where it performs the most critical functions.

Out of this 1 percent, approximately 15% is complexed calcium bound to organic and inorganic anions, 40% is bound to albumin, and the remaining 45% circulates as free ionized calcium.

The Chvostek sign is a clinical finding associated with hypocalcaemia, or low levels of calcium in the blood. This clinical sign refers to a twitch of the facial muscles that occurs when gently tapping an individual’s cheek, in front of the ear.

Prolonged QT interval are associated with hypocalcaemia as reported in multiple studies.

Calcium channel blocker (CCB) blocks L-type of voltage-gated calcium channels present in blood vessels and the heart. By inhibiting the calcium channels, these agents decrease the frequency of opening of calcium channels activity of the heart, decrease heart rate, AV conduction, and contractility.

Three groups of CCBs include
1) Phenylalkylamines: Verapamil, Norverapamil
2) Benzothiazepines : Diltiazem
3) Dihydropyridine : Nifedipine, Nicardipine, Nimodipine, Nislodipine, Nitrendipine, Isradipine, Lacidipine, Felodipine and Amlodipine.

Even though verapamil as good absorption from GIT, its oral bioavailability is low due to high first-pass metabolism.

Nimodipine is a Cerebro-selective CCB, used to reverse the compensatory vasoconstriction after sub-arachnoid haemorrhage and is more lipid soluble analogue of nifedipine

Calcium channel antagonist can potentiate the effect of non-depolarising muscle relaxants.

The deep inguinal ring is the entrance of the inguinal canal. It is an opening in the transversalis fascia around 1 cm above the inguinal ligament. Therefore, the superolateral wall is made by the transervalis fascia.

The inferior epigastric vessels run medially to the deep inguinal ring forming its inferomedial border.

The inguinal canal extends obliquely from the deep inguinal ring to the superficial inguinal ring.
An indirect inguinal hernia arises through the deep inguinal ring lateral to the inferior epigastric vessels.

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.

The anterior cerebral artery supplies the midline portion of the frontal lobe and the superior medial parietal lobe of the brain. It also supplies the front four-fifths of the corpus callosum and provides blood to deep structures such as the anterior limb of the internal capsule, part of the caudate nucleus, and the anterior part of the globus pallidus.

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.

Clinically, the internal carotid arteries and their branches are often referred to as the anterior circulation of the brain. The anterior cerebral arteries are connected by the anterior communicating artery. Near their termination, the internal carotid arteries are joined to the posterior cerebral arteries by the posterior communicating arteries, completing the cerebral arterial circle around the interpeduncular fossa, the deep depression on the inferior surface of the midbrain between the cerebral peduncles.

The middle cerebral artery supplies part of the frontal, temporal and parietal lobes.

The posterior cerebral artery supplies the occipital lobe.

Cardiac output = stroke volume x heart rate

Left ventricular ejection fraction = (stroke volume / end diastolic LV volume ) x 100%

Stroke volume = end diastolic LV volume – end systolic LV volume

Pulse pressure = Systolic Pressure – Diastolic Pressure

Systemic vascular resistance = mean arterial pressure / cardiac output
Factors that increase pulse pressure include:
-a less compliant aorta (this tends to occur with advancing age)
-increased stroke volume

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

The vertebral (spinal) column is the skeletal central axis made up of approximately 33 bones called the vertebrae.

Cervical disc herniations occur when some or all of the nucleus pulposus extends through the annulus fibrosus. The most commonly affected discs are the C5-C6 and C6-C7 discs. Each vertebrae has a corresponding nerve root which arises at a level above it. This means that a hernation of the C5-C6 disc will cause a compression of the C6 nerve root.

The foramen transversarium is a part of the transverse process of each cervical vertebrae, however, the vertebral artery only runs through the C1-C6 foramen transversarium.

The costal facets are the point of joint formation between a rib and a vertebrae. As such, they are only present on the transverse processes of T1-T10.

The lumbar vertebrae do not form a joint with the ribs, nor do they possess a foramina in their transverse process.

Intervertebral discs are thickest in the cervical and lumbar regions of the spinal column. However, there are no discs between C1 and C2.

Dystonia is characterised by repetitive twisting movements or abnormal postures. They are classified as either primary or secondary.

Primary dystonia is a genetic disorder that is inherited in an autosomal dominant pattern.
Secondary dystonia can be caused by focal brain lesions, Parkinson’s disease, or certain medications.

The following drugs cause the most common drug-induced dystonic reactions:
Antipsychotics, antiemetics (especially prochlorperazine and metoclopramide), and antidepressants.

Following the administration of the neuroleptic prochlorperazine, 16 percent of patients experience restlessness (akathisia) and 4% experience dystonia.

Several published reports have linked the anaesthetics thiopentone, fentanyl, and propofol to opisthotonos and other abnormal neurologic sequelae. Dystonias following a general anaesthetic are uncommon. Tramadol has been linked to serotonin syndrome, while remifentanil has been linked to muscle rigidity.

The following are some of the risk factors:

Positive family history
Male
Children
An episode of acute dystonia occurred previously.
Dopamine receptor (D2) antagonists at high doses and recent cocaine use

Dystonia is treated in a variety of ways, including:

Benztropine (as a first-line therapy):

1-2 mg intravenous injection for adults
Child: 0.02 mg/kg to 1 mg maximum

Benzodiazepines are a type of benzodiazepine (second line treatment).

Midazolam:

1-2 mg intravenously, or 5-10 mg IV/PO diazepam

Antihistamines with anticholinergic activity (H1receptor antagonists):

Promethazine 25-50 mg IV/IM, or diphenhydramine 50 mg IV/IM (1 mg/kg in children) are used when benztropine is not available.

When the emergency oxygen flush is pressed, 100% oxygen is supplied from the common gas outlet. This gas bypasses BOTH flowmeters and vaporisers. The flow of oxygen is usually 45 l/min at a PRESSURE OF 400 kPa.

There is an increased risk of pulmonary barotrauma when the emergency flush is pressed, especially when anaesthetising paediatric patients.

The inappropriate use of the flush causes dilution of anaesthetic gases and this increases the possibility of anaesthetic awareness .

Both incidence and prevalence are indicators of the disease frequency. While incidence tells us about the number of cases reported per population in a provided time period, prevalence is the factor you should be vigilant about as it tells us about the total number of cases that have been reported in a population at a particular point of time.

The superficial inguinal ring is an opening in the aponeurosis of the external oblique muscle, just above and lateral to the pubic crest.

The superficial ring resembles a triangle more than a ring with the base lying on the pubic crest and its apex pointing towards the anterior superior iliac spine. The sides of the triangle are crura of the opening in the external oblique aponeurosis. The lateral crura of the triangle is attached to the pubic tubercle. The medial crura of the triangle is attached to the pubic crest.

The external oblique aponeurosis forms the anterior wall of the inguinal canal and also the lateral edge of the superficial inguinal ring. The rectus abdominis lies posteromedially, and the transversalis posterior to this.

Sodium concentration for different fluids
3% N saline 513 mmol/L
5% N saline 856 mmol/L
0.9% N saline 154 mmol/L
Hartmann’s solution 131 mmol/L
0.45% N saline with 5% glucose 77 mmol/L

This means that:

500 mL 5% N saline contains 428 mmol of sodium
1000 mL 3% N saline contains 513 mmol of sodium
3500 mL 0.9% N saline contains 539 mmol of sodium
4000 mL Hartmann’s contains 524 mmol of sodium
6000 mL 0.45% N saline with 5% glucose contains 462 mmol of sodium.

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 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.

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.

The standard error of the mean (SEM) is a measure of the spread expected for the mean of the observations – i.e. how ‘accurate’ the calculated sample mean is from the true population mean. The relationship between the standard error of the mean and the standard deviation is such that, for a given sample size, the standard error of the mean equals the standard deviation divided by the square root of the sample size.

SEM = SD / square root (n)

where SD = standard deviation and n = sample size

Therefore, the SEM gets smaller as the sample size (n) increases.

If we want to depict how widely scattered some measurements are, we use the standard deviation. For indicating the uncertainty around the estimate of the mean, we use the standard error of the mean. The standard error is most useful as a means of calculating a confidence interval. For a large sample, a 95% confidence interval is obtained as the values 1.96×SE either side of the mean.

A 95% confidence interval:

lower limit = mean – (1.96 * SEM)

upper limit = mean + (1.96 * SEM)

Results such as mean value are often presented along with a confidence interval. For example, in a study the mean height in a sample taken from a population is 183cm. You know that the standard error (SE) (the standard deviation of the mean) is 2cm. This gives a 95% confidence interval of 179-187cm (+/- 2 SE).

Hence, it would be wrong to say that confidence levels do not apply to standard error of the mean.

Because alpha glucosidase inhibitors slow starch digestion in the small intestine, glucose from a meal enters the bloodstream more slowly and can be matched more effectively by an impaired insulin response or sensitivity, glucose from a meal enters the bloodstream more slowly and can be matched more effectively by an impaired insulin response or sensitivity.

Biguanides decrease hepatic glucose output while increasing glucose uptake in peripheral cells.

The meglitinides are secretagogues that act on a different site of the KATP receptors.

Insulin secretion is stimulated by sulphonylureas, which stimulate insulin secretion from pancreatic beta cells. The KATP channels are inhibited by these substances.

Insulin-sensitive genes are influenced by thiazolidinediones, which increase the production of mRNAs for insulin-dependent enzymes. As a result, the cells make better use of glucose.