The anterior tibial artery originates from the distal border of the popliteus. In the posterior compartment, it passes between the heads of the tibialis posterior and the oval aperture of the interosseous membrane to reach the anterior compartment.

On entry into the anterior compartment, it runs medially along the deep peroneal nerve.
The upper third of the artery courses between the tibialis anterior and extensor digitorum longus muscles, while the middle third runs between the tibialis anterior and extensor hallucis longus muscles.

At the ankle, the anterior tibial artery is located approximately midway between the malleoli. It continues on the dorsum of the foot, lateral to extensor hallucis longus, as the dorsalis pedis artery.

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

The oesophagus is a muscular tube that connects the pharynx to the stomach. It begins at the lower border of the cricoid cartilage and C6 vertebra. It ends at T11.

The oesophagus has physiological constrictions at the following levels:
1. Cervical constriction: Pharyngo-oesophageal junction (15 cm from the incisor teeth) produced by the cricopharyngeal part of the inferior pharyngeal constrictor muscle
2. Thoracic constrictions:
i. where the oesophagus is first crossed by the arch of the aorta (22.5 cm from the incisor teeth)
ii. where the oesophagus is crossed by the left main bronchus (27.5 cm from the incisor teeth)
3. Diaphragmatic constriction: where the oesophagus passes through the oesophageal hiatus of the diaphragm (40 cm from the incisor teeth)

Awareness of these constrictions is important for clinical purposes when it is required to pass instruments through the oesophagus into the stomach or when viewing radiographs of patients’ oesophagus.

Direct laryngoscopy are performed using laryngoscopes and they can be classed according to the shape of the blade as curved or straight.

Miller, Soper, Wisconsin and Seward are examples of straight blade laryngoscopes. Straight blades are commonly used for intubating neonates and infants but can be used in adults too.

The tip of the miller blade is advanced over the epiglottis to the tracheal entrance then lifted in order to view the vocal cords.

The RIGHT-SIDED Macintosh blade is used in adults while the left-sided blade may be used in conditions that make intubation with standard blade difficult e.g. facial deformities.

The McCoy laryngoscope is based on the STANDARD MACINTOSH blade not Robertshaw’s. It has a lever operated hinged tip, which improves the view during laryngoscopy.

Polio blade is mounted at an angle of 120-135 degrees to the handle. Originally designed for use during the polio epidemic ​in intubation patients within iron lung ventilators, it is now useful in patients with conditions like breast hypertrophy, barrel chest, and restricted neck mobility.

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

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

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

The small and large intestinal walls are composed of the following common layers:
1. Mucosa
2. Submucosa
3. Muscularis Externa
4. Adventitia

Intestinal villi are highly vascular projections of the mucosal surface that cover the entire small intestinal mucosa. They increase the lumen’s surface area, which aids in absorption and digestion, the primary functions of the small intestine. Villi are large and most abundant in the duodenum and jejunum.

In both the small and large intestines, the muscularis mucosae are found within the mucosa. The myenteric nerve plexus is found innervating the muscularis externa. The mucosa is lined with columnar epithelial cells, and goblet cells may be present to secrete mucins.

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

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

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

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

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

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

His energy requirement per day is:

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

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

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

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

1000 mL of 5% dextrose has 50 g of glucose

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

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

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

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

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

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

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

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

Heme a exists in cytochrome a and heme c in cytochrome c; they are both involved in the process of oxidative phosphorylation. 5′-Aminolevulinic acid synthase (ALA-S) is the regulated enzyme for heme synthesis in the liver and erythroid cells.

There are two forms of ALA Synthase, ALAS1, and ALAS2.

The laryngeal folds are comprised of two types of folds; the vestibular fold and the vocal fold. The vocal folds are mobile, and concerned with voice production. They are formed by the mucous membrane covering the vocal ligament. They are avascular, hence, are white in colour.

The internal branch of the superior laryngeal nerve provides sensation above the vocal cords. Lesions to this nerve may lead to loss of sensation above the vocal cords and loss of taste on the epiglottis.

The recurrent laryngeal nerve supplies the lateral and posterior cricoarytenoid, the thyroarytenoid. It also provides sensation below the vocal cords. Lesions to this nerve may cause respiratory obstruction, hoarseness, inability to speak and loss of sensation below the vocal cords.

The external branch of the superior laryngeal nerve supplies the cricothyroid muscle.

The glossopharyngeal nerve contains both sensory and motor components, and provides somatic innervation to the stylopharyngeus muscle, visceral motor innervation to the parotid gland, and carries afferent sensory fibres from the posterior third of the tongue, pharynx and tympanic cavity.

The perfect glomerular filtration marker is:

The human body is not harmed by it.
Chemical or physical methods are used to accurately measure
Extracellular fluid (ECF) compartment is freely and evenly diffusible.
Inability to access the intracellular fluid (ICF) compartment
Filtration in the kidney is the only way to remove it from the blood.

The ideal marker should not be reabsorbed into the bloodstream by the renal tubules or other urinary system components.

Creatinine is an endogenous substance that is filtered freely by the glomerulus and secreted by the proximal tubule. As a result, creatinine clearance consistently underestimates GFR. In healthy people, this overestimation ranges from 10% to 40%, but it is higher and more unpredictable in patients with chronic kidney disease.

The gold standard method of inulin clearance necessitates an intravenous infusion and several hours of timed urine collection, making it costly and time-consuming. Inulin is hard to come by and is difficult to mix and keep as a solution.

Exogenous filtration markers include the following:

Although plasma clearance of 51chromium EDTA is a widely used method in Europe, tubular reabsorption can occur.
Because 125I-iothalamate can be excreted by renal tubules in the urine, it cannot be used in patients who have an iodine assay.

Radioactive substances must be stored, administered, and disposed of according to these methods.

The glomerulus filters para-aminohippuric acid (PAH) freely, and any that remains in the peritubular capillaries is secreted into the proximal convoluted tubules. This marker is used to determine the amount of blood flowing through the kidneys.

A stock dose of Intravenous paracetamol available in the market is 10mg/ml. There is a recommended dose of IV paracetamol according to the profile of the patient (age, co-morbidities, weight).

Weight Recommended Dose Maximum per day
≤10 kg 7.5 mg/kg 30 mg/kg
>10 kg to ≤33 kg 15 mg/kg 60 mg/kg (not exceeding 2 g)
>33 kg to ≤50 kg 15 mg/kg 60 mg/kg (not exceeding 3 g)
>50 kg with additional risk factors for hepatotoxicity 1g 3 g
>50 kg with no additional risk factors for hepatotoxicity 1g 4 g

Special precaution must be observed for patients with hepatocellular insufficiency. The maximum dose per day should not exceed 3g.

Also known as the “product limit estimate’’, the Kaplan-Meier survival plot is used to estimate the true survival function from the collected data.

Using this plot, probabilities of occurrence of an event at a certain point in time can be computed. The successive probabilities are multiplied by any earlier computed probabilities to get the final estimate. For a given population, the survival probability at any particular time on the plot = (number of subjects living at the start – number of subjects who died)/number of subjects living at the start.

The description of a scatter plot is a graphical representation using Cartesian coordinates to display values for more than two variables for data set. It is used for to assess the relationship between 2 different variables.

Spirometry measures the total volume of air that can be forced out in one maximum breath, that is the total lung capacity (TLC), to maximal expiration, that is the residual volume (RV).

It is conducted using a spirometer which is capable of measuring lung volumes using techniques of dilution.

During spirometry, the following measurements can be determined:
Forced vital capacity (FVC)/vital capacity (VC): The maximum volume of air exhaled in one single forced breathe.
Forced expiratory volume in one second (FEV1)
FEV1/FVC ratio
Peak expiratory flow (PEF): the maximum amount of air flow exhaled in one blow.
Forced expiratory flow (mid expiratory flow): the flow at 25%, 50% and 75% of FVC
Inspiratory vital capacity (IVC): The maximum volume of air inhaled after a full total expiration.

Anatomical dead space is measured using a single breath nitrogen washout called the Fowler’s method.

Residual volume and total lung capacity are both measured using the body plethysmograph or helium dilution

The functional residual capacity is usually measured using a nitrogen washout or the helium dilution technique.

The inferior phrenic nerves are at the highest risk of damage as they are the first branches of the abdominal aorta. The potential space at the level of the diaphragmatic hiatus is a potentially useful site for aortic occlusion. However, leaving the clamp applied for more than 10 -15 minutes usually leads to poor outcomes.

The superior phrenic artery branches from the thoracic aorta.

The abdominal aorta begins at the level of the body of T12 near the midline, as a continuation of the thoracic aorta. It descends and bifurcates at the level of L4 into the common iliac arteries.

The branches of the abdominal aorta (with their vertebra level) are:
1. Inferior phrenic arteries: T12 (upper border)
2. Coeliac artery: T12
3. Superior mesenteric artery: L1
4. Middle suprarenal arteries: L1
5. Renal arteries: Between L1 and L2
6. Gonadal arteries: L2 (in males, it is the testicular artery, and in females, the ovarian artery)
7. Inferior mesenteric artery: L3
8. Median sacral artery: L4
9. Lumbar arteries: Between L1 and L4

The action of class 1 anti-arrhythmic is sodium channel blockade. Subclasses of this action reflect effects on the action potential duration (APD) and the kinetics of sodium channel blockade.

Drugs with class 1A prolong the APD and refractory period, and dissociate from the channel with intermediate kinetics.

Drugs with class 1B action shorten the APD in some tissues of the heart, shorten the refractory period, and dissociate from the channel with rapid kinetics.

Drugs with class 1C action have minimal effects on the APD and the refractory period, and dissociate from the channel with slow kinetics.

Mid-shaft fractures of the humerus usually occur after a direct blow to the upper arm, which can occur after a fall or RTAs.
The most important clinical significance of a mid-shaft humeral fracture is an injury to the radial nerve. The radial nerve originates from the brachial plexus and has roots of C5-T1. It crosses the spiral groove on the posterior side of the shaft of the humerus.
On examination, the patient may have a wrist drop, loss or weakness of finger extension, and decreased or absent sensation to the posterior forearm, digits 1 to 3, and the radial half of the fourth digit.

The humeral shaft has two compartments:
1. Anterior:
Brachial artery and vein
Biceps brachii, brachialis, coracobrachialis
Musculocutaneous, median, and ulnar nerves
2. Posterior:
Radial nerve
Triceps

Other significant nerve injuries are:
1. Axillary nerve – surgical neck fracture of the humerus
2. Brachial Artery – supracondylar fracture of the humerus
3. Axillary artery – surgical neck fracture of the humerus, but is relatively uncommon

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.

ANOVA is based upon within group variance (i.e. the variance of the mean of a sample) and between group variance (i.e. the variance between means of different samples). The test works by finding out the ratio of the two variances mentioned above. (Commonly known as F statistic).

Nitroglycerine is rapidly denitrated enzymatically in the smooth muscle cell to release the free radical nitric oxide (NO).

Released NO activated cytosolic guanylyl cyclase which increases cGMP (cyclin guanosine monophosphate) which causes dephosphorylation of myosin light chain kinase (MLCK) through a cGMP-dependent protein kinase.

Reduced availability of phosphorylated (active) MLCK interferes with activation of myosin and in turn, it fails to interact with actin to cause contraction. Consequently, relaxation occurs.

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.

The inferior vena cava is formed by the union of the right and left common iliac veins. This occurs at the L5 vertebral level. The IVC courses along the right anterolateral side of the vertebral column and ascends through the central tendon of the diaphragm at the T8 vertebral level.

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 external laryngeal nerve arises from the superior laryngeal nerve and provides innervation to the cricothyroid muscle.

The other muscles mentioned receive their innervations from the recurrent laryngeal nerve.

T cells function as a part of the body’s adaptive immune system. There are different types of T cells, including:

Cytotoxic T cells: Function as killer cells by releasing cytotoxic granules into the membrane of targeted cells.

T-Helper cells: When activated, they function to activate other immune cell types, assist in antibody production with B cells and releasing cytokines including IL-2.

Memory T cells: Function as to provide immune memory against already encountered antigens.

T cells possess specific glycoproteins and receptors on their surface.

T-Helper cells work with HLA class II antigens on the cell surfaces in order to recognise foreign antigens

T cells survive ranges from a few weeks, to a lifetime depending on the subtype in question.

Immunoglobulins are expressed on the surface of, and secreted by B-lymphocytes.

Native antigens are recognised by B cells. T cells only recognise antigens that have been processed by the cells and presented on the surface of the cell.

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.

Blood vessels (except capillaries and venules) have three distinctive layers (innermost to outermost):
1. Tunica intima
2. Tunica media
3. Tunica adventitia

The tunica media contains smooth muscle cells and is separated from the intima layer by the internal elastic lamina and the adventitia by the external elastic lamina.

Propofol is cleared at the fastest rate at the rate of 60ml/kg/min.

Clearance rate of other drugs are as follows:
– Thiopental: 3.5 ml/kg/min
– Methohexitone: 11 ml/kg/min
– Ketamine: 17 ml/kg/min
– Etomidate: 10-20 ml/kg/min

Salmeterol is a long-acting Beta 2 selective agonist. Therefore it is only used for prophylaxis whereas salbutamol is a short-acting Beta 2 agonist and is thus used for the treatment of acute attacks of asthma.

Salmeterol is 15 times more potent than salbutamol at the Beta 2 receptor but 4 times less potent at the Beta 1 receptor.

Tachyphylaxis to the unwanted side effects commonly occurs, but not to bronchodilation.

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.

A paediatric 19G Tuohy catheter is available that is 5cm in length and has 0.5cm markings

18G Tuohy catheters are generally 9 to 10cm to hub

Distal end of catheter is angled (15 to 30 degrees) and closed to avoid puncturing the dura

Epidural mesh are usually 0.2 microns and are used to filter bacteria and viruses to ensure sterility of procedure

Transparent catheters are 90cm long with diameters depending on gauge size. It has 1cm graduations from 5 to 20cm to ensure they have been inserted amply and removed completely. Distal end is smooth which can be open or closed (with lateral openings)

The magnitude of x determines the rate of change of x. First-order drug kinetics is a good example. Most drugs’ plasma levels are controlled by an exponential process. The rate of change in drug metabolism is proportional to the current plasma concentration (so-called non-linear kinetics).

A tear-away function is just one type of exponential relationship (y = ex), in which e is Euler’s number, x is the power, and e is the base. Natural logarithms rely on Euler’s number.

Euler’s number is a mathematical constant, not a mathematical principle. It’s referred to as an irrational number. This is a number that cannot be expressed as a simple fraction or a ratio.

A line or curve that acts as the limit of another line or curve is known as an asymptote. A washout exponential curve, for example, where the value y represents the plasma concentration of a drug in a single compartment model against time on the x axis. This descending curve approaches but never touches the x axis. This curve is asymptotic to the x axis, which is the curve’s asymptote. An asymptote isn’t just a characteristic of exponential curves.

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

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

The left coronary artery arises from the left posterior aortic sinus and divides into the circumflex arteries and the left anterior descending (LAD) artery.

The right coronary artery arises from the anterior aortic sinus and supplies:
– the right ventricle
– part of the interventricular septum
– the atrioventricular (A-V) node and
– in 85% of cases the inferior part of the left ventricle.
The right coronary artery provides a posterior interventricular branch and a marginal branch that anastomoses with the LAD at the apex.

The oblique vein together with the small, middle and great cardiac veins drain into the coronary sinus, which drains into the right atrium.

The anterior cardiac vein drains directly into the right atrium.

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

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

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

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

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

Osmolarity refers to the osmotic pressure generated by the dissolved solute molecules in 1 L of solvent. Measurements of osmolarity are temperature dependent because the volume of the solvent varies with temperature. The higher the osmolarity of a solution, the more it attracts water from an opposite compartment.

Osmolarity can be computed using the following formulas:

Osmolarity = Concentration x number of dissociable particles; OR
Plasma osmolarity (Posm) = 2([Na+]) + (glucose in mmol/L) + (BUN in mmol/L)

Posm = 2 (144) + 3.5 + 9.5 = 301 mOsm/L

Suppose there is electrical neutrality, the formula will double the cation activity to account for the anions.

Plasma osmolarity (Posm) = 2([Na+] + [K+]) + (glucose in mmol/L) + (BUN in mmol/L)

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

Chi-square test is used to determine the statistically significant different between categorical variables. It also determines the difference between expected frequencies and the observed frequencies.

Mann Whitney U test is used to determine the statistically significant different between two independent groups.

Wilcoxon’s test is the test of dependency. it determines the statistically significant difference between two dependent groups.

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

ANOVA (analysis of variance) is similar to student’s t-test.

ANOVA is a statistical method used to determines the statistically significant difference between the mean of more than two group. In this experiment as we are dealing with three different group, ANOVA is most suitable test to determine the difference between each groups.

Desflurane is a highly fluorinated methyl ethyl ether used for the maintenance of general anaesthesia. It has been identified as a weak triggering anaesthetic of malignant hyperthermia. That, in the absence of succinylcholine, may produce a delayed onset of symptoms.

Fractures to the surgical neck of the humerus are common place as it is the weakest point of the proximal humerus bone.

The structures most likely to be damaged are the axillary nerve and the posterior circumflex humeral artery as they surround the surgical neck.

The radial nerve runs along the radial groove, so injury to it would likely occur with a mid-shaft fracture of the humerus.

The brachial artery is most likely to be injured as a result of a supracondylar fracture of the humerus which increases the risk of volkmaan’s ischemic contractures.

Injury to the musculocutaneous nerve is least likely to happen and it very uncommon.

Taste sensation from the anterior two-thirds of the tongue is carried by chorda tympani, a branch of the facial nerve.

The general somatic sensation of the anterior two-third of the tongue is supplied by the lingual nerve, a branch of the mandibular nerve.

Both general somatic sensation and taste from the posterior third of the tongue are carried by the glossopharyngeal nerve.

All the muscles of the tongue except palatoglossus are supplied by the hypoglossal nerve whereas palatoglossus is supplied by the vagus nerve. (This is because palatoglossus is the only tongue muscle derived from the fourth branchial arch)

The costal elements of the seventh cervical vertebrae form projections known as cervical ribs, which are present in approximately 0.5% – 1 % individuals.

A cervical rib commonly comprises of a head, neck and tubercle. The body of the rib varies from person to person. It extends into the posterior triangle of the neck, where it is either free anteriorly, or attached to the first rib / sternum.

Patients with a cervical rib mostly are asymptomatic and it is usually diagnosed as an incidental finding on chest x-ray. However, in some cases, the subclavian artery and the lower trunk of the brachial plexus are compressed where they pass over the cervical rib. This leads to a condition known as ”neurovascular compression syndrome,” in which these neurovascular structures are compressed between the cervical rib and scalenus anterior.

The most common cause of neurogenic symptoms in approximately 80% of the patients with cervical rib is neck trauma.

In most cases, the tingling, numbness and impaired circulation to the upper limb appears only after puberty. This is because the neck elongates, and the shoulders droop slightly.

The spinal cord and the vertebral canal are as long as each other in early fetal life. The length of the cord increases faster than the growth of the vertebrae during development. By the time of birth, the spinal cord is at the level of the lower border of the 3rd lumbar vertebra, compared to its original position at the level of the 2nd coccygeal vertebra.

Breathing 100% oxygen for three minutes will provide the best reservoir of oxygen during apnoea by oxygenating the functional residual capacity (FRC).

Sitting at 45 degrees might increase the FRC and improve oxygen reserve but not compared with 100% oxygenation.

The following table compares the oxygen reserves in the body following pre-oxygenation with room air and 100% oxygen:

Compartment Factors Room air (mL) 100% O2 (mL)
Lung FAO2, FRC 630 2850
Plasma PaO2, DF, PV 7 45
Red blood cells Hb, TGV, SaO2 788 805
Myoglobin – 200 200
Interstitial space – 25 160

FAO2 = alveolar fraction of oxygen.
FRC = Functional residual capacity.
PaO2 = partial pressure of oxygen dissolved in arterial blood
DF = dissolved form.
PV = plasma volume.
TG = total globular volume .
Hb = haemoglobin concentration.
SaO2 = arterial oxygen saturation

Stopping smoking one month prior to surgery will not be more effective than pre-oxygenation with 100% oxygen though it may reduce postoperative pulmonary complications. Note that both long term and short term abstinence reduces pulse rate and blood pressure thus reducing oxygen consumption and also reduce carboxyhaemoglobin levels.

Blood transfusion will not make a big difference in oxygen reserve, particularly if a blood transfusion is administered within 12-24-hours before surgery.

Heliox (79% helium and 21% oxygen) despite its lower viscosity is unlikely to be more effective than 100% oxygen .

The Delphi technique was developed in the 1950s and is a widely used and accepted method for achieving convergence of opinion concerning real-world knowledge solicited from experts within certain topic areas. Choosing the appropriate subjects is the most important step in the entire process because it directly relates to the quality of the results generated, despite this, there is no exact criterion currently listed in the literature concerning the selection of Delphi participants.

Therefore, due to the potential scarcity of qualified participants and the relatively small number of subjects used in a Delphi study, the ability to achieve and maintain an ideal response rate can either ensure or jeopardize the validity of a Delphi study.

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.

During normal tissue metabolism, there is production of CO2 (acid) which is then expired by the lungs. If metabolism switches from aerobic to anaerobic due to a lack of oxygen, the tissues are unable to completely oxidise sugars to CO2. As a consequence, the sugars can only be partially oxidised to lactic acid. Since lactic acid cannot be expired by the lungs, it remains in the circulation leading to metabolic acidosis.

Also, normal tissue metabolism leads to the production of some amount of acid from the breakdown of proteins. These acids are excreted from the body by kidney filtration. Renal failure will therefore results in acidosis after several days.

An increased acidosis stimulates the brain’s respiratory centres to increase the respiratory rate. This lowers the CO2 in the blood, leading to a decrease in its acidity. Renal excretion removes the excess acid, resulting in a normal pH, and a reduced PaCO2 and HCO3.

pH PaCO2 (kPa) HCO3
Compensated respiratory acidosis 7.34 7.2 29
Acute respiratory acidosis 7.25 7.3 22
Compensated metabolic acidosis 7.34 3.6 14
Metabolic acidosis 7.21 5.3 15
Metabolic alkalosis 7.51 5.1 30

A hernia is a protrusion of the abdominal viscera through a defect in the abdominal wall. Inguinal hernias are of two types; Indirect inguinal hernia and Direct inguinal hernia.
– Indirect inguinal hernia is common at young age commonly due to a patent processes vaginalis and bowel passes through the deep inguinal ring lateral to the inferior epigastric artery.
– Direct hernia forms as a result of the weakening of the posterior wall of the inguinal canal more specifically within a region called ‘Hasselbach triangle. It is defined medially by the rectus abdominis muscle, laterally by the epigastric vessels, and inferiorly by the inguinal ligament.

Direct and indirect hernias can be differentiated based on their relation to the inferior epigastric artery. Direct inguinal hernia lies medial to it while indirect inguinal hernia lies lateral to the inferior epigastric artery.

The femoral ring is the site of the femoral hernia.

The most likely diagnosis is a spinal epidural haematoma, a neurological emergency. A full examination must be carried out to determine the nature of the neurological problem before conducting any investigations or imaging.

The effects of spinal anaesthesia should have worn off by this time point, and the severe back pain is a red flag.

The patient will also require an urgent neurological team referral as a spinal epidural haematoma requires immediate evacuation for spinal decompression. Analgesics may be prescribed for pain management.

Heparin would have been fully metabolised and so a reversal is unnecessary.

A spinal epidural haematoma is a pooling of blood in the epidural space, which can cause compression of the spinal cord. Its presenting symptoms are:

Usually begins with severe backpain and percussion tenderness
Cauda equina syndrome
Paralysis of the lower extremities.
If infected, a fever occurs in 66% of cases
Lower limb weakness developing after stopping an epidural infusion or weakness of the lower limbs which does not resolve within four hours of cessation of infusion of epidural local anaesthetic
Meningism.

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

The borders of the inguinal canal are:

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

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

Roof: formed by the internal oblique and transversus abdominis muscles

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

Chest compressions are an essential part of cardiopulmonary resuscitation (CPR) which helps restore spontaneous circulation (ROSC).

Sodium bicarbonate is only prescribed in patients with cardiac arrests as a result of an overdose of tricyclic antidepressants or hyperkalaemia. Its use causes the body to produce more CO2 which causes:

Exacerbation of intracellular acidosis
Negative inotropy to ischaemic myocardium
Increased osmotic load of sodium into failing brain and body
Shift of oxygen dissociation curve to the left.

THAM is often used to treat metabolic acidosis as a result of cardiac bypass surgery and also cardiac arrest, when other standard methods have failed.

Carbicarb (Na2CO3 0.33 molar NaHCO3 0.33 molar) has only mild effects on acidosis. It also causes an increase in arterial CO2 pressure and lactate concentration.

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

Age more than 70: 05 points

History of myocardial infarction:

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

Angina Pectoris:

Angina with minimal exertion: 10 points

Angina at any level of exertion: 20 points

Pulmonary Oedema:

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

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

Risk classification:

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

Approximately 25% of phase-1 drug reactions is made responsible by CYP2D6.

As much as a 1,000-fold difference in the ability to metabolise drugs by CYP2D6 can happen between phenotypes, and this may result in adverse drug reactions (ADRs).

The metabolism of antiemetics, beta-blockers, codeine, tramadol, oxycodone, hydrocodone, tamoxifen, antidepressants, neuroleptics, and antiarrhythmics is also as a result of CYP2D6.

Patients who take drugs that are metabolised by CYP2D6 but have poor CYP2D6 metabolism are more likely to have ADRs. People with ultra-rapid CYP2D6 metabolism may have a decreased drug effect due to low plasma concentrations of these drugs.

All the other CYP enzymes are subject to genetic polymorphism. Variants are less likely to lead to adverse drug reactions.

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.
2. Left Anterior Descending (LAD) artery – supplies the front and bottom of the left ventricle and front of the interventricular septum

The left anterior descending coronary artery is the largest coronary artery. It courses anterior to the interventricular septum in the anterior interventricular groove, extending from the base of the heart to its apex. Around the apex, the LAD anastomosis with the terminal branches of the posterior descending artery (branch of the right coronary artery).
Atherosclerosis or thrombotic occlusion of LAD causes myocardial infarction in large areas of the anterior, septal, and apical portions of the heart muscle. It can lead to a serious deterioration in heart performance.

Occlusion of the LAD causes anteroseptal myocardial infarction, which is evident on the ECG with changes in leads V1-V4. Occlusion of the left circumflex artery causes lateral, posterior, or anterolateral MI. However, as it does not run towards the apex in the interventricular septum of the heart, it is not the correct answer for this question.

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

The right coronary artery supplies the right atrium, right ventricle, interatrial septum, and the inferior posterior third of the interventricular septum. Occlusion of the right coronary artery causes inferior MI, which is indicated on ECG with changes in leads II, III, and aVF.

Bell’s palsy is facial muscle weakness or paralysis that arises from idiopathic damage to the facial nerve. It can occur at any age but is commonly associated with some conditions:
1. pregnancy
2. diabetes
3. upper respiratory ailment
4. GBS
5. Toxins

The common symptoms of Bell’s palsy are:
1. Abnormal corneal reflex as the facial nerve controls the motor aspect of the corneal reflex.
2. The loss of control of facial muscles and eyelids leads to decreased tear production.
3. mild weakness to total paralysis on one side of the face, occurring within hours to days.
4. Bell’s palsy is a lower motor neuron lesion that usually spares the forehead while the upper motor near lesions, like stroke, involves the entire face.
5. The anterior two-thirds of the tongue is supplied by the chorda tympani branch of the facial nerve, thus resulting in loss of taste.
6. Ptosis can be a feature of Bell’s palsy but Bell’s palsy would typically show unilateral symptoms rather than bilateral.

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.

Trigeminal neuralgia is characterized by excruciating paroxysms of pain in the lips, gums, cheek, or chin and, very rarely, in the distribution of the fifth nerve. The pain seldom lasts more than a few seconds or a minute or two but may be so intense that the patient winces, hence the term tic. The paroxysms, experienced as single jabs or clusters, tend to recur frequently, both day and night, for several weeks at a time. They may occur spontaneously or with movements of affected areas evoked by speaking, chewing, or smiling. Another characteristic feature is the presence of trigger zones, typically on the face, lips, or tongue, that provoke attacks; patients may report that tactile stimuli – e.g., washing the face, brushing the teeth, or exposure to a draft of air – generate excruciating pain. An essential feature of trigeminal neuralgia is that objective signs of sensory loss cannot be demonstrated on examination.

Trigeminal neuralgia is relatively common, with an estimated annual incidence of 4–8 per 100,000 individuals. Middle-aged and elderly persons are affected primarily, and ,60% of cases occur in women. Onset is typically sudden, and bouts tend to persist for weeks or months before remitting spontaneously. Remissions may be long-lasting, but in most patients, the disorder ultimately recurs.

An ESR or CRP is indicated if temporal arteritis is suspected. In typical cases of trigeminal neuralgia, neuroimaging studies are usually unnecessary but may be valuable if MS is a consideration or in assessing overlying vascular lesions in order to plan for decompression surgery.

Tramadol is weak agonist at the mu receptor. It inhibits the neuronal reuptake of serotonin and norepinephrine, and inhibits pain neurotransmission. It is given for moderate pain, chronic pain syndromes, and neuropathic pain.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI). It inhibits the neuronal reuptake of serotonin by inhibiting the serotonin transporter (SERT). It is the drug of choice for major depressive disorder, and is given for other psychiatric disorders such as anxiety, obsessive-compulsive, post-traumatic stress, and phobias.

When tramadol is given with SSRIs, serotonin syndrome may occur. Serotonin syndrome is characterized by fever, agitation, tremors, clonus, hyperreflexia and diaphoresis. The onset of symptoms may occur within a few hours, and the first-line treatment is sedation, paralysis, intubation and ventilation.

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

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

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

When there is a fall in ionised plasma calcium levels, the chief cells of the parathyroid glands are stimulated to secrete parathyroid hormone (PTH).

50% of extracellular calcium occurs as non-ionised, protein- (albumin-)bound calcium.

The degree of ionisation increases with low ph and decreases with high pH.

There is increased renal calcium excretion with secretion of calcitonin.

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

The bispectral index (BIS) monitors works to determine the level of consciousness of a patient by processing electroencephalographic (EEG) signals to obtain a value between 0 and 100, where 0 reflects no brain activity, and 100 reflects a patient is completely awake.

The general meaning of BIS values are:

>95: Patient is in an awake state.
65-85: Patient is in a sedated state.
40-65: Patient is in a state that is optimal for general surgery.
<40: Patient is in a deep hypnotic state It is important in measuring the depths of anaesthesia to prevent haemodynamic changes or patient awareness during surgery. The nature of anaesthetic agent used is a determinant factor in resultant BIS values. Intravenous agents, such as propofol, thiopental and midazolam, result in a deeper hypnotic state, whilst inhalation agents have a lesser hypnotic effect at the same BIS values. Certain agents result in inaccurate BIS values such as ketamine and nitrous oxide (NO). These two agents appear to increase the BIS value, whilst putting the patient in a deeper hypnotic state, and should therefore not be used with BIS monitoring. Hypothermia also affects the BIS value as it causes a 1.12 per °C decrease in body temperature.

Ketamine is primarily used for the induction and maintenance of anaesthesia. It induces dissociative anaesthesia. But it is contraindicated in cardiovascular diseases such as unstable angina or poorly controlled hypertension.

Tricyclic antidepressants (TCA) are primarily used as antidepressants which is important for the management of depression. These are second-line drugs next to SSRI. They work by competitively preventing re-uptake of amines (noradrenaline and serotonin) from the synaptic cleft so increasing their concentration. But TCA overdoses are toxic and have cardiovascular effects, central effects, and anticholinergics effects. Cardiovascular effects like prolonged QT and widened QRS at lower doses progressing to ventricular arrhythmias and refractory hypotension at higher doses can be life-threatening. When used in the perioperative period, it can lead to increased sensitivity to circulating catecholamines therefore care is needed perioperatively.

This patient’s limited haematological profile includes mild normocytic anaemia and a normal platelet count.

Iron deficiency is the most common cause of anaemia during pregnancy. It affects 75 to 95 percent of patients. A haemoglobin level of less than 110 g/L in the first trimester and less than 105 g/L in the second and third trimesters is considered anaemia. There will usually be a low mean cell volume (MCV), mean cell haemoglobin (MCH), and mean cell haemoglobin concentration in addition to a low haemoglobin (MCHC). The MCV may be normal in mild cases of iron deficiency or coexisting vitamin B12 and folate deficiency.

To determine whether you have an iron deficiency, you’ll need to take more tests. Low serum ferritin (15 g/L) and less reliable indices like serum iron and total iron binding capacity are among them.

A number of factors contribute to iron deficiency in pregnancy, including:

Insufficient dietary iron to meet the mother’s and foetus’ nutritional needs
Multiple pregnancies
Blood loss, as well as
Absorption of iron from the gut is reduced.

The volume of plasma increases by about 50% during pregnancy, but the mass of red blood cells (RBCs) increases by only 30%. Dilutional anaemia is the result of this situation. From the first trimester to delivery, the RBC mass increases linearly, while the plasma volume plateaus, stabilises, or falls slightly near term. As a result, between 28 and 34 weeks of pregnancy, haemoglobin concentrations are at their lowest. The effects of haemodilution will be negated in this patient because she is 37 weeks pregnant.

Vitamin B12 and folate deficiency are less common causes of anaemia in pregnancy. The diagnosis could be ruled out if the MVC is normal.

During pregnancy, the platelet count drops, especially in the third trimester. Gestational thrombocytopenia is the medical term for this condition. It’s due to a combination of factors, including haemodilution and increased platelet activation and clearance. Pre-eclampsia and HELLP syndrome are common causes of thrombocytopenia. Pre-eclampsia isn’t the only cause of anaemia during pregnancy.

A typical blood picture of a haemoglobinopathy like sickle cell disease shows quantitative and qualitative defects, with the former leading to a severe anaemia exacerbated by haemodilution and other factors that contribute to iron deficiency. Microcytic cells are the most common type.

Using a lean body weight metric encompasses a more scientific approach to weight-based dosing. Lean body weight reflects the weight of all ‘non-fat’ body components, including muscle and vascular organs such as the liver and kidneys. As lean body weight contributes to approximately 99% of a drug’s clearance, it is useful for guiding dosing in obesity.

This metric has undergone a number of transformations. The most commonly cited formula derived by Cheymol is not optimal for dosing across body compositions and can even produce a negative result. A new formula has been developed that appears stable across different body sizes, in particular the obese to morbidly obese.

A practical downfall of the calculation of lean body weight (and other body size descriptors) is the numerical complexity, which may not be palatable to a busy clinician. Often limited time is available for prescribing and an immediate calculation is required. Lean body weight calculators are available online, for example in the Therapeutic Guidelines.

Using total body weight assumes that the pharmacokinetics of the drug are linearly scalable from normal-weight patients to those who are obese. This is inaccurate. For example, we cannot assume that a 150 kg patient eliminates a drug twice as fast as a 75 kg patient and therefore double the dose. Clinicians are alert to toxicities with higher doses, for example nephro- and neurotoxicity with some antibiotics and chemotherapeutics, and bleeding with anticoagulants. Arbitrary dose reductions or ‘caps’ are used to avoid these toxicities, but if too low can result in sub-therapeutic exposure and treatment failure.

Body surface area is traditionally used to dose chemotherapeutics. It is a function of weight and height and has been shown to correlate with cardiac output, blood volume and renal function. However, it is controversial in patients at extremes of size because it does not account for varying body compositions. As a consequence, some older drugs such as cyclophosphamide, paclitaxel and doxorubicin were ‘capped’ (commonly at 2 m^2) potentially resulting in sub-therapeutic treatment. Recent guidelines suggest that unless there is a justifiable reason to reduce the dose (e.g. renal disease), total body weight should be used in the calculation of body surface area, until further research is done. Little research into dosing based on body surface area has been conducted for other medicines.

Ideal body weight was developed for insurance purposes not for drug dosing. It is a function of height and gender only and, like body surface area, does not take into account body composition. Using ideal body weight, all patients of the same height and sex would receive the same dose, which is inadequate and generally results in under-dosing. For example a male who has a total body weight of 150 kg and a height of 170 cm will have the same ideal body weight as a male who is 80 kg and 170 cm tall. Both could potentially receive a mg/kg dose based on 65 kg (ideal body weight).

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

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

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

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

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

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

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

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

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

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

1. Multiply the standard error by 3.

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

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

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

The porta hepatis is a fissure in the inferior surface of the liver. All the neurovascular structures that enter and leave the porta hepatis are:
1. hepatic portal vein
2. hepatic artery
3. hepatic ducts
4. hepatic nerve plexus (It contains the sympathetic branch to the liver and gallbladder and the parasympathetic, hepatic branch of the vagus nerve.)

These structures supply and drain the liver. Only the hepatic vein is not part of the porta hepatis.
The porta hepatis is also surrounded by lymph nodes, that may enlarge to produce obstructive jaundice.
These structures divide immediately after or within the porta hepatis to supply the functional left and right lobes of the liver.

The cystic duct lies outside the porta hepatis and is an important landmark in laparoscopic cholecystectomy.

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

Metabolic equivalent (MET) measures the energy expenditure of an individual.

It is calculated mathematically by:

MET = (VO2 max/weight)/3.5 = 21/3.5 = 6 METs

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)

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)

Bernoulli’s principle states that as the speed of a moving fluid increases, there is a simultaneously decrease in static pressure or a decrease in the fluid’s potential energy.
This is seen in the simultaneous increase in speed and kinetic energy and fall in pressure that causes entrainment of large volumes of air into a flow of 100% oxygen in the nozzle of HAFOE masks.

The reduction in fluid pressure that happens when a fluid flows through a constriction in a tube is the Venturi effect.

When a flow of gas or liquid attaches itself to a nearby surface and remains attached even when the surface curves away from the initial direction of flow, this is the Coanda effect.

The branch of engineering and technology that is concerned with the building of devices that use the flow and pressure of a fluid for functions usually performed by electronic devices is Fluidics . Fluidic logic is used to power some ventilators.

The branch of engineering that utilises pressurised gases is Pneumatics.

The emulsification and absorption of fats requires Bile salts.

Absorption of fats is associated with the activation of lipases in the intestine.

Bile salts are involved in fat soluble vitamin absorption and are reabsorbed in the terminal ileum (B12 is NOT fat soluble).

Although Vitamin B12 is also absorbed in the terminal ileum, it is a water soluble vitamin (as are B1, nicotinic acid, folic acid and vitamin C) .

The gastric parietal cells secretes Intrinsic factor that is essential for the absorption of B12.

The solid state of matter has a definite volume and shape and particles are packed closely together and are incompressible. Within this tight lattice, there is enough thermal energy to produce vibration of particles.

Liquids however have a volume but no definite shape. These particles are less tightly packed together. Although there is free movement within the volume, they are incompressible.

Gases, however, have no finite shape or volume and particles are free to move rapidly in a state of random motion. They are compressible and are completely shaped by the space in which they are held. Vapours exist as a gas phase in equilibrium with identical liquid or solid matter below its boiling point.

The most prevalent state of matter in the universe is plasma which is formed by heating atoms to very high temperatures to form ions.

Serum specific IgE assays against allergen sources/molecules are the most commonly used in vitro diagnostic approach. The measurement of specific IgE recognizing allergenic epitopes can be achieved both through the usage of single reagents (singleplex) or with a pre-defined panel of a number of molecules to be tested simultaneously (multiplex).

Several clinical entities have been described and those occurring immediately after drug exposure are immunoglobulin E (IgE)-mediated and explored by skin testing and by the in vitro measurement of serum-specific IgE. The sensitivity of these tests is not 100% and even for patients with a clear positive history, a drug provocation test may be required in order to confirm the diagnosis. The advantages of the in vitro determination of specific IgE antibodies when compared with in vivo testing are that the former poses no direct risk to the patient and does not require personnel with expertise. Even though in vitro tests are recommended in immediate hypersensitivity reactions, their exact place in the diagnostic procedure is not clear and certain authors do not use this method in daily practice. In one study, in terms of sensitivity, 11 of 26 patients (42%) with negative skin tests and a positive drug provocation challenge (or repeated clinical history) had specific IgE to benzylpenicilloyl or amoxicilloyl (4). The specificity of the test was 95–100%. Therefore, IgE measurements can avoid a potentially harmful drug provocation test.

An elevated serum tryptase does not differentiate between type 1 and type 2 hypersensitivity reaction. It indicates mast cell degranulation.

RAST is a useful aid to improve the overall diagnosis of drug allergies by using radioactive detection. This, however, is now rarely used.

Quantification of basophil activation by CD63 expression can be done by flow cytometry, which forms the basis of experimental drug-induced basophil stimulation tests.

When a person forcefully expires against a closed glottis, changes occur in intrathoracic pressure that dramatically affect venous return, cardiac output, arterial pressure, and heart rate. This forced expiratory effort is called a Valsalva maneuver.

Initially during a Valsalva, intrathoracic (intrapleural) pressure becomes very positive due to compression of the thoracic organs by the contracting rib cage. This increased external pressure on the heart and thoracic blood vessels compresses the vessels and cardiac chambers by decreasing the transmural pressure across their walls. Venous compression, and the accompanying large increase in right atrial pressure, impedes venous return into the thorax. This reduced venous return, and along with compression of the cardiac chambers, reduces cardiac filling and preload despite a large increase in intrachamber pressures. Reduced filling and preload leads to a fall in cardiac output by the Frank-Starling mechanism. At the same time, compression of the thoracic aorta transiently increases aortic pressure (phase I); however, aortic pressure begins to fall (phase II) after a few seconds because cardiac output falls. Changes in heart rate are reciprocal to the changes in aortic pressure due to the operation of the baroreceptor reflex. During phase I, heart rate decreases because aortic pressure is elevated; during phase II, heart rate increases as the aortic pressure falls.

When the person starts to breathe normally again, the intrathoracic pressure declines to normal levels, the aortic pressure briefly decreases as the external compression on the aorta is removed, and heart rate briefly increases reflexively (phase III). This is followed by an increase in aortic pressure (and reflex decrease in heart rate) as the cardiac output suddenly increases in response to a rapid increase in cardiac filling (phase IV). Aortic pressure also rises above normal because of a baroreceptor, sympathetic-mediated increase in systemic vascular resistance that occurred during the Valsava.

Incidence tells us about the number of new cases that have been reported while prevalence gives us the idea of existing cases.

In this particular instance, the parameter of the study i.e. the total number of cases has not changed thus the prevalence of the disease remains same. Although, more cases have been reported in the second instance as a result of which incidence has increased.

The derived unit of energy, work or amount of heat is joule (J). It is defined as the amount of energy expended if a force of one newton (N) is applied through a distance of one metre (N·m)

J = 1 kg·m/s2·m = 1 kg·m2/s2 or 1 kg·m2·s-2

Kinetic energy (KE) = ½ MV2

An object with a mass of 1500 kg moving at 30 m/s correlates to 675 kJ:

KE = ½ (1500) × (30)2 = 750 × 900 = 675 kJ

Total energy released when 1 kg fat is metabolised to CO2 and water is 37 MJ. 1 g fat produces 37 kJ/g, therefore 1 kg fat produces 37,000 × 1000 = 37 MJ.

Raising the temperature of 1 kg water from 0°C to 100°C correlates to 420 kJ. The amount of energy needed to change the temperature of 1 kg of the substance by 1°C is the specific heat capacity. We have 1 kg water therefore:

4,200 J × 100 = 420,000 J = 420 kJ

In order to calculate the energy involved in raising a 100 kg mass to a height of 1 km against gravity, we need to calculate the potential energy (PE) of the mass:

PE = mass × height attained × acceleration due to gravity
PE = 100 kg × 1000 m × 10 m/s2 = 1 MJ

The heat generated when a direct current of 10 amps flows through a heating element for 10 seconds when the potential difference across the element is 1000 volts can be calculated by applying Joule’s law of heating:

Work done (WD) = V (potential difference) × I (current) × t (time)
WD = 10 × 10 × 1000 = 100 kJ

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.

Lesser the potency of the drug, the higher the dose required to produce maximal receptor occupation. So, the least potent drug will have a log dose-response curve furthest to the right on X-axis.

Based on the option given, tramadol is the least potent drug and thus higher dose is required to produce maximal opioid receptor occupation.

Thus, Tramadol is the least potent opioid with a log dose-response curve furthest to the right on X-axis.

Note, Fentanyl is the most potent opioid with a log dose-response curve furthest to the left on the X-axis.

Half life (T½) is the time required to change the amount of drug in the body by one-half (or 50%) during elimination. The time course of a drug in the body will depend on both the volume of distribution and the clearance.

Extrapolating the values from the plasma concentration vs time:

Plasma concentration at 0 hours = 800 mcg/mL
Plasma concentration at 2 hours = 400 mcg/mL
Plasma concentration at 4 hours = 200 mcg/mL
Plasma concentration at 6 hours = 100 mcg/mL
Plasma concentration at 8 hours = 50 mcg/mL
Plasma concentration at 10 hours = 25 mcg/mL
Plasma concentration at 12 hours = 12.5 mcg/mL
Plasma concentration at 14 hours = 6.25 mcg/mL

Venous cutdown is a surgical procedure when venous access is difficult, and other procedures like the Seldinger technique, ultrasound-guided venous access, and intraosseous vascular access have failed.

The vein of choice for venous cutdown is the long/great saphenous vein. It is part of the superficial venous collecting system of the lower extremity. It is the preferred vein as the long saphenous vein has anatomic consistency and is superficially located at the ankle anterior to the medial malleolus. It is also the most commonly used conduit for cardiovascular bypass operations.

Origin- in the foot at the confluence of the dorsal vein of the first digit and the dorsal venous arch of the foot
Route- runs ANTERIOR to the medial malleolus and travels up in the medial leg and upper thigh.
Termination: in the femoral vein within the femoral triangle

Regarding the other options:
The short saphenous vein passes posterior to the lateral malleolus.
The dorsalis pedis vein accompanies the dorsalis pedis artery on the anterior foot.
The posterior tibial vein is part of the deep venous system accompanying the posterior tibial artery. There is no significant sural vein (there is a sural nerve), but the sural veins accompany the sural arteries and drain to the popliteal vein.

An elevated arterial blood lactate level and an increase anion gap ([Na + K] – [Cl + HCO3]) of >20mmol gives rise to lactic acidosis. It can also be a result of overproduction and/or reduced metabolism of lactic acid.

The liver and kidney are the main sites of lactate metabolism, not skeletal muscle.

The two types of lactic acidosis that are known are:

Type A – due to tissue hypoxia, inadequate tissue perfusion and anaerobic glycolysis. These may be seen in cardiac arrest, shock, hypoxaemia and anaemia. The management of type A lactic acidosis involves reversing the underlying cause of the tissue hypoxia.

Type B – occurs in the absence of tissue hypoxia. Some of the causes of this include hepatic failure, renal failure, diabetes mellitus, pancreatitis and infection. Some drugs can also cause this lie aspirin, ethanol, methanol, biguanides and intravenous fructose.

The mainstay of treatment involves:
1. Optimising tissue oxygen delivery
2. Correcting the cause
3. Intravenous sodium bicarbonate

In resistant cases, peritoneal dialysis can be performed.

A pulse oximeter is a piece of medical equipment used as a non-invasive method of measuring the oxygen saturation of blood.

It works by measuring the ratio of absorption of red and infrared light in a section of blood flow, as red light is largely absorbed by deoxygenated blood, and infrared light is largely absorbed by oxygenated blood.

Pulse oximetry relies on photoplethysmography (PPG) waveforms. The oximeter has 2 sides, with different functions. One side houses light-emitting diodes which are responsible for transmitting 2 light wavelengths, 660nm for red light and 940nm for near infrared light. The other side is a photodetector. The light emitted travels through the body and the amount that is not absorbed is measured by the photodetector.

Smokers often have increased levels of carboxy haemoglobin (COHb). This leads to artificial increases in pulse oximeter readings as it is unable to differentiate between COHb and oxyhaemoglobin (O2HB) as they both absorb red light at 660nm. Every 1% increase of circulating carboxyhaemoglobin, results in a correlative 1% increase in oximeter readings.

Prilocaine toxicity will cause an artificial decrease in oximeter readings. This is because prilocaine metabolites cause methemoglobinemia (MetHB), which are dysfunctional haemoglobins unable to properly transport oxygen. In this case, a laboratory multiwavelength co-oximeter is recommended for a more accurate reading.

Anaemia will not affect oximeter readings as long as haemoglobins in the blood are normal.

Sickle cell disease does not affect oximeter readings despite its ability to cause hypoxia and shift the oxygen dissociation curve to the right.

Brown-red fingernail polish will cause an underestimation of pulse oximeter readings.

The ideal volatile agent for a day case surgery inhalational induction should have the following characteristics:

It has a pleasant scent that is not overpowering.
Breathing difficulties, coughing, or laryngeal spasm are not caused by this substance.
The action has a quick onset and a quick reversal.

The blood:gas partition coefficient is a physicochemical property of a volatile agent that determines the onset and offset of anaesthesia. The greater an agent’s insolubility in plasma, the faster its alveolar concentration rises.

The blood gas partition coefficients of the most commonly used volatile anaesthetic agents are as follows:
Halothane 2.3
Desflurane 0.45
Sevoflurane 0.6
Nitrous oxide 0.47
Isoflurane 1.4

Although halothane has a pleasant odour, it has a slower offset than sevoflurane.

Sevoflurane also has a pleasant odour and is less likely than desflurane to cause airway irritation and breath-holding.

The choice of agent for inhalational induction is unaffected by potency/lipid solubility measures such as the oil: gas partition coefficient and MAC.

In this case, an agent’s saturated vapour pressure is irrelevant.

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.

Glutamic acid decarboxylase is responsible for the catalyses of glutamate to gamma-aminobutyric acid (GABA)

Catechol-o-methyl transferase catalyses the degradation and inactivation of dopamine into 3-methoxytyramine, epinephrine into metanephrine, and norepinephrine into normetanephrine and vanylmethylmandelic acid (VMA).

Monoamine oxidase catalyses the oxidation of norepinephrine to vanylmethylmandelic acid (VMA) and serotonin to 5-hydeoxyindole acetic acid (5-HIAA).

Cholinesterase functions to catalyse the split of acetylcholine into choline and acetic acid.

The wall of an artery has three layers: (innermost to outermost)
1. Tunica intima – in direct contact with the blood inside the vessel and contains endothelial cells separated by gap junctions.
2. Tunica media – contains smooth muscle cells and is separated from the intima by the internal elastic lamina and the adventitia by the external elastic lamina.
3. Tunica adventitia – contains the vasa vasorum, fibroblast, and collagen.

Aortic dissection is when a tear arises in the innermost layer of the aorta and penetrates through the tear, entering the media layer. The inner and middle layers of the aorta split (dissect).

The arteries of the midgut (superior mesenteric artery) and hindgut (inferior mesenteric artery) give off terminal branches that form an anastomotic vessel called the marginal artery of Drummond. It runs in the inner margins of the colon and gives off short terminal branches to the bowel wall.

The marginal artery is formed by the main branches and arcades arising from the ileocolic, right colic, middle colic, and left colic arteries. It is most apparent in the ascending, transverse, and descending colons and poorly developed in the sigmoid colon.

Being the part of a meta analysis, forest plots are more valued as evidence then randomised control trials.

The notion that forest plots can only be used if the results are substantial is not true. They are good indicators of the significance of the data. If the diamond intersects the central line, the data is rendered significant. It also aggregates means and confidence intervals from studies conducted in the past which makes the study much more reliable as errors associated with individual studies tend to have less of an impact in this way.

The suggestion that forest plots are primarily used for qualitative data is factually incorrect. Forest plots require numerical values to function.

All in all, forest plots help us in determining whether or not there is a significant trend in that particular field of study.

Thermodilution is the most common dilution method used to measure cardiac output (CO) in a hospital setting.

During the procedure, a Swan-Ganz catheter, which is a specialized catheter with a thermistor-tip, is inserted into the pulmonary artery via the peripheral vein. 5-10mL of a cold saline solution with a known temperature and volume is injected into the right atrium via a proximal catheter port. The solution is cooled as it mixes with the blood during its travel to the pulmonary artery. The temperature of the blood is the measured by the catheter and is profiled using a computer.

The computer also uses the profile to measure cardiac output from the right ventricle, over several measurements until an average is selected.

Cardiac output changes at each point of respiration, therefore to get an accurate measurement, the same point during respiration must be used at each procedure, this is usually the end of expiration, that is the end-expiratory pause.

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.

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.

The electrons in the outer shell of an oxygen molecule are unpaired, thus it has paramagnetic properties and is attracted into a magnetic field.

It utilizes null deflection -True
Null deflection is a crucial principle in paramagnetic analysers (reflected beam of light on two photocells) which gives very accurate results (typically 0.1%).

It can be used to measure the concentration of diamagnetic gases – False
Since most other gases are weakly diamagnetic they are repelled by a magnetic field (nitric oxide is also paramagnetic).

Can measure gases dissolved in the blood – False
For accurate analysis the sample gas must be dried before passing into the analysis cell, for example, by passage through silica gel. Therefore, they are unsuitable to measure gases dissolved in blood.

Does not require calibration – False
As with most measurement instruments paramagnetic analysers must be calibrated before use.

E) The readings are unaffected by water vapour – False
Water vapour affects the readings hence for accurate analysis the sample gas must be dried before passing into the analysis cell, for example, by passage through silica gel. That is why they are unsuitable to measure dissolved blood gases.

Epoprostenol has a half-life of only 42 seconds and has rapid offset. It is used for the treatment of pulmonary hypertension.

Aspirin inhibits the COX enzyme irreversibly. It inhibits thromboxane synthesis but does not inhibit the enzyme thromboxane synthetase.

Ticlopidine, clopidogrel and prasugrel act as irreversible antagonists of P2 Y12 receptor of Adenosine Diphosphate (ADP). These drugs interfere with the activation of platelets by ADP and fibrinogen. Both aspirin and clopidogrel act irreversibly so they are not correct.

Paclitaxel is a long-acting antiproliferative agent used for the prevention of restenosis (recurrent narrowing) of coronary and peripheral stents and is not the correct answer.

Tirofiban has the next shortest duration of action after epoprostenol. If epoprostenol is not given in the question, it would be the best answer.

Tetracyclines inhibit protein synthesis through reversible binding to bacterial 30s ribosomal subunits (not 50s) which prevent binding of new incoming amino acids (aminoacyl-tRNA) and thus interfere with peptide growth.

They penetrate macrophages and are thus a drug of choice for treating infections due to intracellular organisms.

Tetracycline does not inhibit transpeptidation. Meanwhile, it is chloramphenicol which is responsible for inhibiting transpeptidation.

Tetracycline can get deposited in growing bone and teeth due to its calcium-binding effect and thus causes dental discoloration and dental hypoplasia. Due to this reason, they should be avoided in pregnant or lactating mothers.

Simultaneous administration of aluminium hydroxide can impede the absorption of tetracyclines.

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

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

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

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

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

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.

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

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

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

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

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

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

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

An echocardiograph (ECG) is not necessary in this case

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

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

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.

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

The ascending cervical artery lies media the phrenic nerve on scalenus anterior and can easily be mistaken for the phrenic nerve at operation.

The phrenic nerve passes across scalenus anterior and medius inferiorly.

The subclavian artery is separated from the vein by the scalenus anterior.

The brachiocephalic vein is formed at the medial border of scalenus anterior by the subclavian vein and the internal jugular vein.

Emerging from the lateral border of scalenus anterior are the trunks of the brachial plexus .

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.

The peritoneal cavity is made up of the omentum, the ligaments and the mesentery.

The section of the peritoneum responsible for tethering organs to the posterior abdominal wall is the mesentery.

These tethered organs are classified as intraperitoneal, and these include the stomach, spleen, liver, first and fourth parts of the duodenum, jejunum, ileum, transverse, and sigmoid colon.

Retroperitoneal organs are located posterior to the peritoneum and include: the rest of the duodenum, the ascending colon, the descending colon, the middle third of the rectum, and the remainder of the pancreas

A beta-1 adrenoreceptor agonist is most likely the ligand that causes increased automaticity, increased chronotropy, increased excitability, and increased inotropy on the sino-atrial node. However, alpha-1 adrenoreceptor effects may cause an increase in systemic vascular resistance. Noradrenaline, adrenaline, dopamine, and ephedrine are examples of drugs with mixed alpha and beta effects.

Adrenaline, noradrenaline, dopamine, dopexamine, dobutamine, ephedrine, and isoprenaline are examples of drugs that have some beta-1 activity. The beta-1 receptor is a G protein-coupled metabotropic receptor. When the beta-1 agonist binds to the cell surface membrane, it causes a conformational change in the Gs unit, which triggers a cAMP-dependent pathway and a calcium influx into the cell.

Catecholamines also help to relax the heart muscle (positive lusitropy). Dromotropy is the ability to increase the atrioventricular (AV) node’s conduction velocity.

Inodilators cause an increase in intracellular calcium as a result of phosphodiesterase III (PDIII) inhibition. Milrinone, enoximone, and amrinone are some examples. Positive inotropy is caused by increased calcium entry into the myocytes. Lusitropy is also increased by phosphodiesterase inhibitors. Increased cAMP inhibits myosin light chain kinase, resulting in reduced phosphorylation of vascular smooth muscle myosin, lowering systemic and pulmonary vascular resistance.

The mechanism of action of alpha-1 adrenoreceptor agonists is an increase in intracellular calcium caused by an increase in inositol triphosphate (IP3). IP3 is a second messenger that causes an increase in systemic vascular resistance by stimulating the influx of Ca2+ into smooth muscle cells. Reflex bradycardia can occur as a result of the subsequent increase in blood pressure. Phenylephrine and metaraminol are examples of pure alpha-1 agonists.

Levosimendin is a novel inotrope that makes myocytes more sensitive to intracellular Ca2+. It causes a positive inotropy without changing heart rate or oxygen consumption significantly.

The Na-K-ATPase membrane pump in the myocardium is inhibited by digoxin. This inhibition promotes sodium-calcium exchange, resulting in an increase in intracellular Ca2+ and increased contraction force. The parasympathetic effects of digoxin on the AV node result in bradycardia. Systemic vascular resistance will not be affected by it.

In first order kinetics the rate of elimination is proportional to plasma concentration.

Rate of elimination is described by the following equation:

C = C0. e^-kt

Where:
C=drug concentration,
C0= drug concentration at time zero (extrapolated),
k = rate constant and
t = time.

The initial concentration of this drug is 12 mcg/ml therefore:

The plasma concentration will have halved to 6 mcg/ml at 2 hours.
The plasma concentration will have halved to 3 mcg/ml at 4 hours and
The plasma concentration will have halved to 1.5 mcg/ml t 6 hours.

Work up bias involves comparing the novel diagnostic test with the current standard test. A portion of the patients undergo the standard test while others undergo the new test as the standard test is costly. The result can be alteration in specify and sensitivity.

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

Not publishing the results of a valid study just because they are negative or uninteresting can be termed as publication bias.

When information gathering is ill suited with respect to time i.e. collecting the data regarding a fatal disease many years after the death of its patients, it is termed as Late – look bias.

The case in point is an instance of lead time bias when upon comparing two tests, one is able to detect the condition earlier than the other but the overall outcome doesn’t change. There is a possibility that this will make the survival rates for the newer test look more promising.

Bupivacaine is used to decrease sensation in a specific area. It is injected around a nerve that supplies the area, or into the spinal canal’s epidural space.

The maximum volume of 0.5% bupivacaine that should be administered to a 10kg child is 5 ml

The common hepatic artery arises from the celiac artery and has the following branches:
1. hepatic artery proper that branches into –
a. cystic artery to supply the gallbladder
b. left and right hepatic arteries to supply the liver
2. gastroduodenal artery that branches into
a. right gastroepiploic artery
b. superior pancreaticoduodenal artery
3. right gastric artery

The pancreatic artery is a branch of the splenic artery.

Increasing temperature increases the amount of water vapour contained in air; for example, at 20°C, air contains about 17 g/m3, and at 37°C, air contains about 44 g/m3. The wet and dry bulb hygrometer, like the hair hygrometer, measures relative humidity.

Under normal operating conditions, Heat and moisture exchangers (HMEs) allows relative humidity of up to 70% to be achieved. Mucus can impair their performance, and they should not be used for longer than 24 hours.

Hot water bath humidifiers might cause scalding, condensed water in the tubing can interfere with gas flow, and there is a danger of infection.

The ultrasonic humidifier operates at roughly 2 MHz and may attain relative humidity levels much above 100%.

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

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

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

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

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

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

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

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

It can be found as:

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

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

So,

ARR= (165/1050)-(132/1044)

ARR= (0.157-0.126)

ARR= 0.031

NNT= 1/0.031

NNT=32.3

Bilirubin is the tetrapyrrole and a catabolic product of heme. 70-90% of bilirubin is end product of haemoglobin degradation in the liver.

Bilirubin circulates in the blood in 2 forms; unconjugated and conjugated bilirubin.

Unconjugated bilirubin is insoluble in water. It travels through the bloodstream to the liver, where it changes from insoluble into a soluble form (i.e.; unconjugated into conjugated form).

This conjugated bilirubin travels from the liver into the small intestine and the gut bacteria convert bilirubin into urobilinogen and then into urobilin (not urobilin to urobilinogen). A very small amount passes into the kidneys and is excreted in urine.

The international system of units, or system international d’unites (SI) is a collection of measurements derived from expanding the metric system.

There are seven base units, which are:

Metre (m): a unit of length
Second (s): a unit of time
Kilogram (kg): a unit of mass
Ampere (A): a unit of electrical current
Kelvin (K): a unit of thermodynamic temperature
Candela (cd): a unit of luminous intensity
Mole (mol): a unit of substance.

This clinical trial consists over 1000 patients being evaluated for the response to a new treatment against a currently licensed treatment for ulcerative colitis. Therefore, it is comparing its efficacy to an established therapeutic or control in a larger population of volunteers. These are the characteristics of a phase III clinical trial.

When the convulsion lasts for five or more than five minutes, or if there are recurrent episodes of convulsions in a 5 minute period without returning to the baseline, it is termed as Status Epilepticus.
The first priority in the patient with seizures is maintaining the airway, breathing, and circulation.

Guideline for the management of Status Epilepticus in children by Advanced Life Support Group is as follow:

Step 1 (Five minutes after the start of seizures):

If intravascular access is available start treatment with lorazepam 0.1 mg/kg IV
If no intravascular access then give buccal midazolam 0.5 mg/kg or rectal diazepam 0.5 mg/kg.

Step 2 (Ten minutes after the start of seizure):

If the convulsions continue then a second dose of benzodiazepine should be given. Senior should be called on-site and phenytoin should be prepared.
No more than two doses or benzodiazepines should be given (including any doses given before arrival at the hospital)
If still no IV access then obtain intraosseous access (IO).

Step 3 (Ten minutes after step 2)

Senior help along with anaesthetic/ICU help should be sought
Phenytoin 20 mg/kg IV over 20 minutes
If the seizure stops before the full dose of phenytoin is given then the infusion should be completed as this provides up to 24 hours of anticonvulsant effect
In children already receiving phenytoin as treatment for epilepsy then an alternative is phenobarbitone 20 mg/kg IV over five minutes
Once the phenytoin is started, senior staff may wish to give rectal paraldehyde 0.4 mg/kg although this is no longer included in the routine algorithm recommended by APLS.

Step 4 (20 minutes after step 3)

If 20 minutes after starting phenytoin the child remains in status epilepticus then rapid sequence induction of anaesthesia with thiopentone and a short acting paralysing agent is needed and the child transferred to paediatric intensive care.

Ketamine is a phencyclidine (hallucinogenic) derivative that is administered in a dose of 2 mg/kg and acts by blocking NMDA (N-methyl-D-aspartate) receptors of glutamate.

It is a powerful bronchodilator agent and is, therefore, an intravenous anaesthetic of choice in bronchial asthma (halothane is an inhalational anaesthetic agent of choice for bronchial asthma). It is also used in the management of refractory status epilepticus.

It is an acid solution with an elimination half-life of three hours.

It has S (+) enantiomer and R (-) enantiomer. the S(+) enantiomer is two to four times more potent than the R(-) and is less likely to produce hallucinations.

Its use is contraindicated in patients with ischaemic heart disease because it increased sympathetic outflow leading to tachycardia and increased cardiac output which in turn increases the myocardial oxygen demand.

Phosphate is the principal anion of the intracellular fluid, most of which is bound to either lipids or proteins. They dissociate or associate with different compounds, depending on the enzymatic reaction, thus forming a constantly shifting pool.

Calcium and magnesium are also present intracellularly, however in lesser amounts than phosphate.

Sodium is the most abundant extracellular cation, and Chloride and is the most abundant extracellular anion.

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

Loop diuretics act by causing inhibition of Na+ K+ 2Cl– symporter present at the luminal membrane of the ascending limb of the loop of Henle.

Furosemide, torsemide, bumetanide, ethacrynic acid, furosemide, piretanide, tripamide, and mersalyl are the important members of this group

The main use of loop diuretics is to remove the oedema fluid in renal, hepatic, or cardiac diseases. Thus they are useful in the treatment of acute heart failure. These can be administered i.v. for prompt relief of acute pulmonary oedema (due to vasodilatory action).

Hypokalaemia, hypomagnesemia, hyponatremia, alkalosis, hyperglycaemia, hyperuricemia, and dyslipidaemia are seen with both thiazides as well as loop diuretics

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

So,

ARR= (24/120)-(60/240)

ARR= 0.2-0.25

ARR= 0.05 (Numerical Value)

ARR= 5%

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.

Caudal analgesia using bupivacaine is a widely employed technique for achieving both intraoperative and early postoperative pain relief. 0.5 ml/kg of 0.25% plain bupivacaine is favoured by many practitioners who employ this fixed scheme for procedures involving sacral dermatomes (circumcision, hypospadias repair) as well as lower thoracic dermatomes (orchidopexy). However, there are other dosing regimens for caudal blocks with variable analgesic success rates: These include 0.75 ml/kg, 1.0 ml/kg and 1.25 ml/kg.

A study indicated that plain bupivacaine 0.25% at a dose of 0.75 ml/kg compared to a dose of 0.5 ml/kg when administered for herniotomies provided improved quality of caudal analgesia with a low side effects profile. There were consistently more patients with favourable objective pain scale (OPS) scores at all timelines, increased the time to the analgesic request with similar postoperative consumption of paracetamol in the group of patients who received 0.75 ml/kg of 0.25% bupivacaine.

30 mmol Na+ and 30 mmol Cl- are found in 1 litre of 0.18 percent N. saline with 4% dextrose. Percent (percent) refers to the number of grammes of a compound per 100 mL, so a litre of 4 percent dextrose solution contains 40 grammes.

As a result, a 500 mL bag of 1/5th N. saline and 4% dextrose contains approximately 15 mequivalents of sodium and 20 g of glucose. It is hypotonic due to its osmolarity of 284.

Because of the risk of hyponatraemia, it is no longer considered the crystalloid of choice for fluid maintenance in children.

Sucralfate is an octasulfate of glucose to which Al(OH)3 has been added. It undergoes extensive cross-linking in an acidic environment and forms a polymer which adheres to the ulcer base for up to 6 hours and protects it from further erosion. Since it is not systemically absorbed it is virtually devoid of side effects. However, it may cause constipation in about 2% of cases due to the Aluminium component in it.

Sucralfate does not have antibacterial action against Helicobacter pylori. However, Bismuth has antibacterial action due to its oligodynamic effect.

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

RQ = CO2 eliminated/O2 consumed

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

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

The RQ for carbohydrates is = 1.0

The RQ for the rest of the compounds are:

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

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

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.

Asthma is a lung condition that causes reversible narrowing and swelling of airway passages. It is classified by the frequency and severity of symptoms.

The following are symptoms of moderate asthma:

Symptoms include cough, wheezing, chest tightness, or difficulty breathing which occurs daily
Decreased activity levels due to flare-ups
Night-time symptoms 5 or more times a month
Lung function test FEV1 is 60-80% of predicted normal values
Peak flow has more than 30% variability

With moderate asthma attacks, the arterial pCO2 levels may decrease, but as severity increases, so does the pCO2, reaching normal levels, and then exceeding them in severe asthma attacks.

Airway obstruction increases the functional residual capacity.

Concentration of serum bicarbonate would not increase in moderate asthma, but it could possibly increase in life-threatening asthma via the same mechanism as what increases arterial PCO2.

FEV1 is a good measure of airway obstruction. and is reduced in acute asthma attacks.

In the case of a pneumothorax, a decrease in arterial PO2 is higher.

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.

Immunoglobulin E (IgE) are an antibody subtype produced by the immune system. They are the least abundant type and function in parasitic infections and allergy responses.

The most predominant type of immunoglobulin is IgG. It is able to be transmitted across the placenta to provide immunity to the foetus.

IgE is involved in the type I hypersensitivity reaction as it stimulates mast cells to release histamine. It has no role in type 2 hypersensitivity.

Its concentration in the serum is normally the least abundant, however certain reactions cause a rise in its concentration, such as atopy, but not in acute asthma.

The patellar (knee jerk) reflex is a monosynaptic stretch reflex arising from L2-L4 nerve roots. It occurs after a tap on the patellar tendon which causes the spindles of the quadriceps muscles to stretch.

The afferent nerve pathway occurred through A gamma fibres.

Wesphal’s sign refers to a reduction, or absence of the patellar reflex. It is often indicated of a neurological disease affecting the PNS.

A transection of the spinal cord results in a degree of shock which causes all reflexes to be reduced or completely absent, and required a period of approximately 6 weeks to recover.

Boyle’s law is correctly stated as it states that the volume of a gas of known mass is inversely proportional with absolute pressure, at a constant temperature.

Beer’s law states that radiation absorption by a solution of known thickness and concentration is identical to that of a solution of double thickness and half concentration.

Bougner’s (or Lambert’s) law states that every layer with the same thickness will absorb the same amount of radiation as it passes through.

Graham’s law states that the diffusion rate of a gas is inversely related to the square root of its molecular weight.

Raoult’s law states that the reduction of a solvent’s vapour pressure is directly proportional to the solute’s molar concentration.

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

1) Delta opioid receptor

2) Mu opioid receptor

3) Kappa opioid receptor

4) Orphan receptor-like 1

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

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

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

Bulky, greasy stools are associated with improper digestion that can be expected if the pancreas loses its exocrine function. This is common in long-term chronic pancreatitis but since this is the patient’s first presentation with such symptoms, this complication is unlikely.

Peripheral neuropathy is a common complication of chronic diabetes but has been reported with cases of chronic pancreatitis too.

Abdominal distention with shifting dullness is a classic symptom of underlying ascites. Ascites is a complication of many diseases but it is not common with the acute first-time presentation of pancreatitis.

Option E: This points towards abdominal obstruction but in the absence of the more common symptoms, nausea and bilious vomiting, this is unlikely.

Option A: Grey Turner’s sign is the pooling of blood in the retroperitoneal space between the last rib and the top of the hip. The pancreas is a retroperitoneal organ and inflammation of the pancreas can cause retroperitoneal haemorrhage. The sign takes 24-48 hours to develop and can predict a severe attack of acute pancreatitis. The patient has presented with acute pancreatitis due to his history of high alcohol intake, and acute on chronic is unlikely as this is his first presentation. He also has low blood pressure and an increased heart rate, which suggest blood loss with acute pancreatitis.

Automated blood gas analysers are commonly used to analyse blood gas samples, and they measure specific components of the arterial blood gas sample, whether directly or indirectly.

The following are the components of arterial blood gas:

pH = measured (directly determined) acid-base balance of the blood

PaO2 = measured partial pressure of oxygen in arterial blood

PaCO2 = measured partial pressure of carbon dioxide in arterial blood

HCO3 = calculated (indirectly determined) concentration of bicarbonate in arterial blood

Base excess/deficit = calculated relative excess or deficit of base in arterial blood

SaO2 = calculated arterial oxygen saturation unless a co-oximetry is obtained, in which case it is measured

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.

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.

The sacral hiatus is shaped by incomplete midline fusion of the posterior elements of the distal portion of S4 and S5. This inverted U shaped space is covered by the posterior aspect of the sacrococcygeal membrane and is an important landmark in caudal anaesthetic block. Distal most portion of the dural sac and the sacral hiatus usually terminate between levels S1 and S3. The dural sac ends at the level of S2 in adults and S3 in children.

An equilateral triangle is formed between the apex of the sacral hiatus and the posterior superior iliac spines. This triangle is used to determine the location of the sacral hiatus during caudal anaesthetic block.

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

CaO2 = oxygen bound to haemoglobin + oxygen dissolved in plasma

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

where:

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

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

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

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

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

The 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.

The extrinsic pathway is best assessed by the PT time.

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

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

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

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

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

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

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

The 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.

The cricoid cartilage is a hyaline cartilage ring surrounding the trachea. It provides support for key phonation muscles.

The inferior border of the cricoid cartilage is attached to the thyroid cartilage and the inferior border is attached to the first tracheal ring through the cricotracheal ligament.

Application of pressure to the cricoid cartilage to reduce risk of aspiration of gastric contents (Sellick manoeuvre) does not stop tracheal aspiration and cannot stop regurgitation into the oesophagus.

A force of 44 newtons to the cricoid cartilage is needed to control regurgitation.

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause bronchospasm, rhinorrhoea, and nasal obstruction in some asthma patients.

The inhibition of cyclooxygenase-1 (Cox-1) appears to be the cause of NSAID-induced reactions. This activates the lipoxygenase pathway, which increases the release of cysteinyl leukotrienes (Cys-LTs), which causes bronchospasm and nasal obstruction.

The following changes in arachidonic acid (AA) metabolism have been observed in NSAID-intolerant asthmatic patients:

Prostaglandin E2 production is low, possibly due to a lack of Cox-2 regulation.
An increase in leukotriene-C4 synthase expression and
A decrease in the production of metabolites (lipoxins) released by AA’s transcellular metabolism.

Phospholipase A produces membrane phospholipids, which are converted to arachidonic acid.

TXA2 causes vasoconstriction as well as platelet aggregation and adhesion.

PGI2 causes vasodilation and a reduction in platelet adhesion.

PGE2 is involved in parturition initiation and maintenance, as well as thermoregulation.

Magnesium is a unique calcium antagonist as it can act on most types of calcium channels in vascular smooth muscle and as such would be expected to decrease intracellular calcium. One major effect of decreased intracellular calcium would be inactivation of calmodulin-dependent myosin light chain kinase activity and decreased contraction, causing arterial relaxation that may subsequently lower peripheral and cerebral vascular resistance, relieve vasospasm, and decrease arterial blood pressure.

The vasodilatory effect of MgSO4 has been investigated in a wide variety of vessels. For example, both in vivo and in vitro animal studies have shown that it is a vasodilator of large conduit arteries such as the aorta, as well as smaller resistance vessels including mesenteric, skeletal muscle, uterine, and cerebral arteries.

The theory of cerebrovascular vasospasm as the aetiology of eclampsia seemed to be reinforced by transcranial Doppler (TCD) studies which suggested that MgSO4 treatment caused dilation in the cerebral circulation as well as in animal studies that used large cerebral arteries.

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

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

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

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

The surface marking for locating the femoral artery is the mid-inguinal point, which is the halfway point between the anterior superior iliac spine (ASIS) and the pubic symphysis.

The other mentioned options are not specific for any landmark.

However, it is important to note the difference between the mid inguinal point and the midpoint of the inguinal ligament, which is travels from the ASIS to the pubic tubercle.

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.

Nitrous oxide increases cerebral blood flow by direct cerebral stimulation and tends to elevate intracranial pressure (ICP)

It increases the cerebral metabolic rate of oxygen consumption (CMRO2)

It is not an NMDA agonist as it antagonizes NMDA receptors.

Cerebral autoregulation is impaired with the use of nitrous oxide but when used with propofol, it is maintained.

Carbon dioxide reactivity is not affected by it.

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.

The data is ideal for chi square test evaluation as it will help determine if observed outcomes are in line with expected outcomes, and also if results are significant or due to chance.

The student’s t test is not ideal as it requires comparison of means from different populations, rather than proportions.

Pearson’s coefficient of linear regression is not ideal as it requires the plotting of a linear regression.

The numbers should be analysed before determining if there are any statistical conclusions that can be drawn from the population.

Statistical analysis is always required to determine the performance of any treatment during a clinical drug trial. Conclusions cannot be drawn simply by looking at the data.

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

The external carotid has eight branches, 3 from its anterior surface ; thyroid, lingual and facial. The pharyngeal artery is a medial branch. The posterior auricular and occipital are posterior branches.

The answer is anterior to the spermatic cord.

The inguinal canal in men contains the ilioinguinal nerve, the genitofemoral nerve and the spermatic cord.

The ilioinguinal nerve arises of the L1 nerve root with the Iliohypogastric nerve, before entering the inguinal canal from the side, through the muscles of the abdomen, travelling superficial to the spermatic cord.

Reflexes are a routine part of clinical examination. Hyperreflexia (abnormally brisk reflexes) is the sign of upper motor neuron damage whereas diminished or absent jerks are most commonly due to lower motor neuron lesions. Reflexes may be Monosynaptic (deep tendon reflexes) or polysynaptic (superficial reflexes)

Here are deep tendon reflexes with their nerve root
Biceps = C5, C6
Supinator (Brachioradialis) = C5, C6
Triceps = C6, C7
Knee reflex = L3,L4
Ankle reflex = S1

Polysynaptic superficial reflexes with their nerve root are listed below
Planter response = S1-2
Abdominal reflexes = T8-12
Cremasteric reflex = L1-2

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 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