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.

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

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

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

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

The maximum safe amount of bupivacaine is 2mg/kg. Addition of adrenaline slows down absorption of the local anaesthetic and allows a maximum dose of 2.5mg/kg to be used.

The maximum safe dose of bupivacaine for this patient is 125 mg.

A 0.125% solution will contain 0.125g/100mL or 125mg/100 mL.

The maximum volume of local anaesthetic is approximately 80-100 mL.

Fentanyl is a pethidine congener, 80–100 times more potent than morphine, both in analgesia and respiratory depression. Fentanyl is ten times more potent than alfentanil.

Alfentanil has a more rapid onset than fentanyl even if fentanyl is more lipid-soluble because both are basic compounds and alfentanil has lower pKa, so a greater proportion of alfentanil is unionized and is more available to cross membranes.

Elimination of alfentanil is higher than fentanyl due to its lower volume of distribution.

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

SEM = SD / square root (n)

where SD = standard deviation and n = sample size

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

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

A 95% confidence interval:

lower limit = mean – (1.96 * SEM)

upper limit = mean + (1.96 * SEM)

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

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

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).

Arrhythmias and/or hypotension are the most common causes of death from tricyclic antidepressant (TCA) overdose.

The quinidine-like actions of tricyclic antidepressants on cardiac tissues are primarily responsible for their toxicity. Conduction through the His-Purkinje system and the myocardium slows as phase 0 depolarisation of the action potential slows. QRS prolongation and atrioventricular block are caused by slowed impulse conduction, which also contributes to ventricular arrhythmias and hypotension.

Arrhythmias can also be caused by abnormal repolarization, impaired automaticity, cholinergic blockade, and inhibition of neuronal catecholamine uptake, among other things.

Acidaemia, hypotension, and hyperthermia can all exacerbate toxicity.

The anticholinergic effects of tricyclic antidepressants, as well as the blockade of neuronal catecholamine reuptake, cause sinus tachycardia. Sinus tachycardia is usually well tolerated and does not require treatment. It can be difficult to tell the difference between sinus tachycardia and ventricular tachycardia with QRS prolongation.

A QRS duration of more than 100 milliseconds indicates a higher risk of arrhythmia and should be treated with systemic sodium bicarbonate.

The tricyclic is dissociated from myocardial sodium channels by serum alkalinization, and the extracellular sodium load improves sodium channel function.

Damping is the reduction of energy in a system achieved by reducing the amplitude of oscillations. It is necessary to some degree to prevent wave overshoots.

Critical damping usually causes the system to be slow, so optimal damping is normally applied to provide a balance between speed and distortion.

Damping can cause errors if excessive (overdamping) or inadequate (Underdamping). The amount of damping in a system can be determined using the damping coefficient (D), where:

Undamped: 0
Critically damped: 1
Optimally damped: 0.64

An overdamped system will cause an artificial decrease in the systolic blood pressure, and an artificial increase in the diastolic blood pressure.

An underdamped system will cause an artificial increase in systolic blood pressure and an artificial decrease in diastolic blood pressure.

Damping can be caused by a number of factors affecting different parts of the system, including:

The tubing/cannula: The presence of air bubbles, increased blood viscosity or formation of blood clots.
The diaphragm/tubing: Increased malleability/compliance
The tubing: Presence of kinks, narrowing or too many ports of injection.

The answer here is a damped system will have a low systolic pressure, a high diastolic pressure with a normal mean pressure.

Pulse oximeters combine the principles of oximetry and plethysmography to noninvasively measure oxygen saturation in arterial blood. A sensor containing two or three light emitting diodes and a photodiode is placed across a perfused body part, commonly a finger, to be transilluminated. Oximetry depends on oxyhaemoglobin and deoxyhaemoglobin, and their ability to absorb the beams of light produced by the light emitting diodes: red light at 660 nm and infrared light at 960 nm.

The isosbestic point is the point wherein two different substances absorb light to the same extent. For oxyhaemoglobin and deoxyhaemoglobin, the points are at 590 nm and 805 nm. These are considered reference points where light absorption is independent of the degree of saturation.

Non-constant absorption of light is often due to the presence of an arterial pulsation, whilst constant absorption of light is seen in non-pulsatile tissues.

Most pulse oximeters are inaccurate at low SpO2, but is accurate at +/- 2% within the range of 70% to 100% SpO2. All pulse oximeters demonstrate a delay in between changes in SaO2 and SpO2, and display average readings every 10 to 20 seconds, hence they are unable to detect acute desaturation episodes.

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

CO2 produced / O2 consumed = RQ

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

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

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

Fats:
RQ = 0.7

Proteins:
Approximately 0.9 RQ

Ethyl alcohol is a type of alcohol.

200/300 = 0.67 RQ

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

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

Mivacurium, when administered at doses greater than 0.2 mg/kg,increases the risk for hypotension, tachycardia, and erythema. This is due to the ability of mivacurium to release histamine with increasing dose. Contrary to this fact, anaphylaxis is rare for mivacurium because of the short duration of histamine release.

The effective dose 50 (ED50) of mivacurium is between 0.08-0.15 mg/kg. It is administered slowly to prevent and decrease the risk of developing adverse effects.

Mivacurium has a high potency thus a longer duration of action, however this is not the answer that we are looking for.

Although drug metabolism takes longer for mivacurium than succinylcholine, it has no effect on the dose required for intubation.

Ciprofloxacin belongs to the quinolone group of antibiotics, and doxycycline and minocycline are tetracyclines. So, they are not affected by beta-lactamase.
However, amoxicillin is a beta-lactam antibiotic and beta-lactamase cleaves the beta-lactam ring present in amoxicillin. This results in the breakdown of the antibiotic and thus the area of erythema dramatically increased.
Co-amoxiclav contains amoxicillin and clavulanic acid which protects amoxicillin from beta-lactamase.

Noradrenaline acts as a sympathomimetic effect via alpha as well as a beta receptor. However, they have weak ?2 action.

Natural catecholamines are Adrenaline, Noradrenaline, and Dopamine

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.

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

Impaired ventricular relaxation reduces diastolic filling and therefore preload.

Decreased blood volume decreases preload due to reduced venous return.

Heart failure is characterized by reduced ejection fraction and therefore stroke volume.

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 (is increased by stroke volume) = 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
Aortic stenosis would decrease stroke volume as end systolic volume would increase.
This is because of an increase in afterload, an increase in resistance that the heart must pump against due to a hard stenotic valve.

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.

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.

Among the types of muscles, cardiac muscles have the greatest number if mitochondria due to the heart energy requirements.

Approximately 35% of the cardiac muscle volume is due to the mitochondria. While in skeletal and smooth muscles, it comprises 3-8% of the muscle volume.

Type I muscle fibre has a slow contraction velocity, with a red fibre colour, and predominantly uses oxidative phosphorylation to produce a sustained contraction. It contains more mitochondria and myoglobin than type II, and is often used for endurance training.

Type II muscle fibre has a fast contraction velocity, a white fibre colour, and predominantly uses anaerobic glycolysis. It has fewer mitochondria and myoglobin, and is often used for weight or resistance training and sprinting.

Impaired ventricular relaxation reduces diastolic filling and therefore preload.

Decreased blood volume decreases preload due to reduced venous return.

Heart failure is characterized by reduced ejection fraction and therefore stroke volume.

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 (is increased by stroke volume) = 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
Aortic stenosis would decrease stroke volume as end systolic volume would increase.
This is because of an increase in afterload, an increase in resistance that the heart must pump against due to a hard stenotic valve.

Major surgery induces the systemic inflammatory response and this causes endothelial leakage and a low albumin level.

Albumin is a single polypeptide which is made but not stored in the liver. Therefore, levels are a reflection of synthetic activity. It is negatively charged and very soluble.

Only 40% of albumin is intravascular, and the rest in the in interstitial compartment.

If there was normal liver function during starvation, albumin will be maintained and proteolysis will occur elsewhere.
It is not catabolised during starvation.
Starvation and malnutrition may, however, present as part of other disease processes that are associated with hypalbuminaemia.

Causes of low albumin are

1. Decreased production (hepatic dysfunction)
2. Increased loss (renal dysfunction)
3. Redistribution (endothelial leak/damage)
4. Increased catabolism (very rare)

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

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

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

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

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

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

The positive predictive value is the ratio of patients truly diagnosed as positive to all those who had positive test results. In this case, this is 60/(60+20)=75%.

The negative predictive value is the ratio of patients truly diagnosed as negative to all those who had negative test results. In this case, this is 80/(80+40)=67%.

The sensitivity is the ratio of patients with the disease who test positive i.e. true positive patients to the total number of people with the disease. In this case, this is 60/(60+40)=60%.

The specificity is the ratio of people who don’t have the disease who test negative i.e. true negatives to the total number of people without the disease. In this case, this is 80/(20+80)=80%.

70% is not the result of any screening measurements

The Kappa Statistic or Cohen’s Kappa is a statistical measure of inter-rater reliability for categorical variables. It is used when two raters both apply a criterion based on a tool to assess whether or not some condition occur. A good example can be two doctors rating individuals for diabetes occurrence on the basis of symptoms.

It gives a quantitative measure of the magnitude of agreement between observers.

Kappa can take any value between 0 and 1. 0 implies the observers are in complete disagreement and a value of 1 implies complete agreement.

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

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

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

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

The taeniae coli are the three outer muscular bands of the cecum, ascending colon, transverse colon, and descending colon.

The taeniae coli converge at the base of the appendix in the cecum where they form a complete longitudinal layer. In the ascending and descending colon, the bands are located anteriorly, posteromedially, and posterolateral.

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

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

The bucks fascia lies within the penis.

Propofol infusion syndrome (PRIS) is characterized by lactic acidosis, bradyarrhythmia, rhabdomyolysis, cardiac and renal failure, and often leads to death. So, lactate monitoring is advised in patients with propofol infusion syndrome.

Ketamine is usually used as a racemic mixture, i.e. (R/S)-ketamine. For over 20 years, use of the more potent (S)-enantiomer by anaesthesiologists has become a preferred option due to the assumption of increased anaesthetic and analgesic properties, a more suitable control of anaesthesia, and of an improved recovery from anaesthesia.

The use of ketamine in anaesthesia and psychiatry may be accompanied by the manifestation of somatic and especially psychomimetic symptoms such as perceptual disturbances, experiences of dissociation, euphoria, and anxiety.

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

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

The arteries: Next are the left and right hepatic arteries

The veins: Next is the portal vein

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

Key Point: While finding out confidence intervals, standard errors are used. Standard error and Standard deviation are two distinct entities and should not be confused.

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

Multiply the standard error by 3.

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

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

The range turns out to be 1-13 mmol/L.

For a confidence interval of 68%, multiply the standard error with 1 and repeat the process. The range found for this interval is 3-11 mmol/L.

For a 95% confidence interval. Standard Error is multiplied by 1.96 which gives us the limit ranging from 3.08 to 10.92 mmol/L which could be approximated to 3-11 mmol/L.

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

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

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

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

The posterior tibial artery originates from the popliteal artery in the popliteal fossa. It passes posterior to the popliteus muscle to pierce the soleus muscle. It descends between the tibialis posterior and flexor digitorum longus muscles.

The posterior tibial artery supplies blood to the posterior compartment of the lower limb. The artery can be palpated posterior to the medial malleolus.

There are 4 main pulse points for the lower limb:

1. Femoral pulse 2-3 cm below the mid-inguinal point
2. Popliteal partially flexed knee to loosen the popliteal fascia
3. Posterior tibial behind and below the medial ankle
4. Dorsal pedis dorsum of the foot over the navicular bone

The hazard ratio (HR) is simply a comparison of two hazards in a study. It provides an estimate of the ratio of the hazard rates between the experimental group and a control group over the entire study duration. It is typically used when analysing survival over time, hence is the most suitable statistical method in this case.

An odds ratio is a statistic that quantifies the strength of the association between two events, A and B. It is the “measure of association” for a case-control study.

The Pearson product-moment correlation coefficient (Pearson’s correlation, for short) is a measure of the strength and direction of association that exists between two variables. An example would be if scientists wanted to evaluate the relationship between quality of certain population of rice and their genetic make-up.

Relative risk is the ratio of the risks for an event for the exposure group to the risks for the non-exposure group. Thus relative risk provides an increase or decrease in the likelihood of an event based on some exposure. Relative risk measures the association between the exposure and the outcome.

Absolute risk reduction is the number of percentage points your own risk goes down if you do a preventive act such as stop drinking alcohol. It depends on what your risk factors are to begin with.

The left gastric artery is the smallest branch that originates from the coeliac trunk—the coeliac trunk branches of the abdominal aorta at the vertebral level of T12.

The left gastric artery runs along the superior portion of the lesser curvature of the stomach. A peptic ulcer that is serious enough to erode through the stomach mucosa into a branch of the left gastric artery can cause massive blood loss in the stomach, leading to hematemesis. The patient also takes Naproxen, a non-steroidal anti-inflammatory drug that is a common cause for peptic ulcers in otherwise healthy patients.

The left gastric artery is responsible for 85% of upper GI bleeds. In cases refractory to initial treatment, angiography is sometimes needed to embolise the vessel at its origin and stop bleeding. During an angiogram, the radiologist will enter the aorta via the femoral artery, ascend to the level of the 12th vertebrae and then enter the left gastric artery via the coeliac trunk.

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

T12 – Coeliac trunk

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

The popliteal fossa is the shallow, diamond-shaped depression located in the back of the knee joint.

The structures that lie within in from superficial to deep are:

The tibial and common fibular nerve: Most superficial. They arise from the sciatic nerve.
The popliteal vein
The popliteal artery: Lies deepest. It arises from the femoral artery

Boundaries of the popliteal fossa:

Laterally
Biceps femoris above, lateral head of gastrocnemius and plantaris below

Medially
Semimembranosus and semitendinosus above, medial head of gastrocnemius below

Floor
Popliteal surface of the femur, posterior ligament of knee joint and popliteus muscle

Roof
Superficial and deep fascia

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

Ascites

Grade of encephalopathy

Serum bilirubin (?mol/L)

Serum Albumin (g/L)

Prothrombin time or INR

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

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

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

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

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

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.

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 Purkinje system, as well as the action potentials of ventricular and atrial myocytes, have the same ionic changes. It lasts about 200 milliseconds and has a resting membrane potential, as well as fast depolarisation and plateau phases.

There are five stages to the process:

Increased Na+ and decreased K+ conductance in Phase 0 (rapid depolarisation).
1st phase (initial repolarisation) : Na+ conductance decreased, while K+ conductance increased.
Phase two (plateau phase) : Ca2+ conductance increased
Phase three (repolarisation phase) : Lower Ca2+ conductance and higher K+ conductance
4th Phase (resting membrane potential) : K+ conductance increased, Na+ conductance decreased, and Ca2+ conductance decreased.

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

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

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

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

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

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

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

Ferromagnetism is the property of a substance that is magnetically attracted and can be magnetised indefinitely. A material is said to be paramagnetic if it is attracted to a magnetic field. A substance is said to be diamagnetic if it is repelled by a magnetic field.

Cobalt, iron, gadolinium, neodymium, and nickel are ferromagnetic.

Gadolinium is a ferromagnetic rare earth metal that is ferromagnetic below 20 degrees Celsius (its Curie temperature). MRI scans are enhanced with gadolinium-based contrast media.

When ferromagnetic materials are exposed to a magnetic field, they can cause a variety of issues like magnetic field interactions, heating, and image artefacts.

Titanium, lead, chromium, copper, aluminium, silver, gold, and tin are non ferromagnetic.

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

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 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.

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

Pulmonary vascular resistance (PVR) refers to the resistance to blood flow to the left atrium from the pulmonary artery.
It is derived mathematically by:

PVR = MPAP – PCWP
CO
where,
MPAP: Mean pulmonary artery pressure
PCWP: Pulmonary capillary occlusion pressure
CO: Cardiac output

For this patient:
PVR = 10 – 5 = 1mmHg
5

Remember, multiply by correction factor 80 to change units:

PVR = 1mmHg x 80 = 80 dynes·s·cm-5

Normal values range between 20-130 dynes·s·cm-5

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 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.

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

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

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

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

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

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

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

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

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.

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

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

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

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

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

In anaesthesia, adductor pollicis neuromuscular monitoring with ulnar nerve stimulation is commonly used. It is the gold standard for measuring the degree of block and comparing neuromuscular blocking drugs and their effects on other muscles.

Electrodes are usually placed over the ulnar nerve at the wrist to monitor the adductor pollicis.

Neuromuscular blocking drugs have different sensitivity levels in different muscle groups.

To achieve the same level of blockade, the diaphragm requires 1.4 to 2 times the amount of neuromuscular blocking agent as the adductor pollicis muscle. The small muscles of the larynx and the ocular muscles are two other respiratory muscles that are less resistant than the diaphragm (especially corrugator supercilii).

The abdominal muscles, Orbicularis oculi, peripheral muscles of the limbs, Geniohyoid, Masseter, and Upper airway muscles are the most sensitive to neuromuscular blocking agents.

The C8-T1 nerve roots, which are part of the medial cord of the brachial plexus, form the ulnar nerve. It enters the hand via the ulnar canal, superficial to the flexor retinaculum, after following the ulnar artery at the wrist.

The nerve then splits into two branches: superficial and deep. The palmaris brevis is supplied by the superficial branch, which also provides palmar digital nerves to one and a half fingers. The dorsal surface of the medial/ulnar 1.5 fingers, as well as the corresponding skin over the hand, are also supplied by it (as well as the palmar surface).

The ulnar nerve’s deep branch runs between the abductor and flexor digiti minimi, which it supplies. It also innervates the opponens, and with the deep palmar arch, it curves around the hook of the hamate and laterally across the palm. All of the interossei, the medial two lumbricals, the adductor pollicis, and, in most cases, the flexor pollicis brevis are supplied there.

This scenario describes rebreathing management.

Changes is exhaustion of the soda lime and a progressive rise in circuit deadspace is the most likely explanation for the capnograph.

It is important that the soda lime canister is inspected for a change in colour of the granules. Initially fresh gas flow should be increased and then if necessary, replace the soda lime granules. Other strategies include changing to another circuit or bypassing the soda lime canister after the fresh gas flow is increased.

Any other causes of increased equipment deadspace should be excluded.

Intraoperative hypercarbia can be caused by:

1. Hypoventilation – Breathing spontaneously; drugs which include anaesthetic agents, opioids, residual neuromuscular blockade, pre-existing respiratory or neuromuscular disease and cerebrovascular accident.
2. Controlled ventilation- circuit leaks, disconnection, miscalculation of patient’s minute volume.
3. Rebreathing – Soda lime exhaustion with circle, inadequate fresh gas flow into Mapleson circuits, increased breathing system deadspace.
4. Endogenous source – Tourniquet release, hypermetabolic states (MH or thyroid storm) and release of vascular clamps.
5. Exogenous source – Absorption of CO2 absorption from the pneumoperitoneum.

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

The cardiac action potential has several phases which have different mechanisms of action as seen below:

Phase 0: Rapid depolarisation – caused by a rapid sodium influx.
These channels automatically deactivate after a few ms.

Phase 1: caused by early repolarisation and an efflux of potassium.

Phase 2: Plateau – caused by a slow influx of calcium.

Phase 3 – Final repolarisation – caused by an efflux of potassium.

Phase 4 – Restoration of ionic concentrations – The resting potential is restored by Na+/K+ATPase.
There is slow entry of Na+into the cell which decreases the potential difference until the threshold potential is reached. This then triggers a new action potential

Of note, cardiac muscle remains contracted 10-15 times longer than skeletal muscle.

Different sites have different conduction velocities:
1. Atrial conduction – Spreads along ordinary atrial myocardial fibres at 1 m/sec

2. AV node conduction – 0.05 m/sec

3. Ventricular conduction – Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec, the fastest conduction in the heart. This allows a rapid and coordinated contraction of the ventricles

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.

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

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

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

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

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

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 electrical conduction system of the heart starts with the SA node which generates spontaneous action potentials.

This is conducted across both atria by cell to cell conduction, and occurs at around 1 m/s. The only pathway for the action potential to enter the ventricles is through the AV node in a normal heart.
At this site, conduction is very slow at 0.05ms, which allows for the atria to completely contract and fill the ventricles with blood before the ventricles depolarise and contract.

The action potentials are conducted through the Bundle of His from the AV node which then splits into the left and right bundle branches. This conduction is very fast, (,2m/s), and brings the action potential to the Purkinje fibres.

Purkinje fibres are specialised conducting cells which allow for a faster conduction speed of the action potential (,2-4m/s). This allows for a strong synchronized contraction from the ventricle and thus efficient generation of pressure in systole.

Cephalosporin belongs to a family of beta-lactam antibiotics. All ?-lactam antibiotics 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 i.e. they inhibit bacterial cell wall formation.

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.

The basilic vein is one of the primary veins that drain the upper limb, like the cephalic vein. It begins as the dorsal venous arch. The basilic vein originates from the ulnar side of the dorsal arch of the upper limb passes along the posteromedial aspect of the forearm, moving towards the anterior surface of the elbow.

The basilic vein pierces the deep fascia at the elbow and joins the venae commitantes of the brachial vein to form the axillary vein.

The basilic vein passes deep under the muscles as it moves midway up the humerus. At the lower border of the teres major muscle, the anterior and posterior circumflex humeral veins feed into it.

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

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

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

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

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

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

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

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

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

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

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

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

The following are some methods for reducing blood volume:

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

The following are some methods for reducing CSF volume:

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

The tricuspid valve allows the tip of a pulmonary artery catheter to pass through the right atrium and into the right ventricle.

The balloon will be inflated before crossing the pulmonary valve and entering the pulmonary artery, where it will eventually wedge or occlude the artery, providing an indirect measure of left atrial pressure.

0-12 mmHg in the right atrium
2-25 mmHg in the right ventricle
12-25 mmHg in the pulmonary artery
8-12 mmHg is the occlusion pressure

Warming, humidifying, and filtering inspired anaesthetic gases is done by heat and moisture exchangers (HME) and breathing system filters. They are made of glass fibres materials and are supported by a sturdy frame. Pleating increases the surface area to reduce resistance to air flow and boost efficiency.

Filters’ effectiveness is determined by the amount and size of particles they keep out of the patient’s airway. The efficiency of filters might be classified as 95, 99.95, or 99.97 percent. Pores with a diameter of 0.2 µm are common. The following are examples of typical particle sizes:
Red blood cell – 5 µm
Lymphocyte – 5-8 µm
Viruses – 0.02-0.3 µm
Bacteria – 0.5-1 µm
Depending on particle size, gas flow speed, and charge, particles are collected via a number of processes. Mechanical sieve, interception, diffusion, electrostatic filtration, and inertial impaction are some of the options:

Sieve:
The diameter of the particle the filter is supposed to collect is smaller than the apertures of the filter’s fibres.

Interception:
When a particle following a gas streamline approaches a fibre within one radius of itself, it becomes attached and captured.
Diffusion:

A particle’s random (Brownian) zig-zag path or motion causes it to collide with a fibre.
By attracting and capturing a particle from within the gas flow, it generates a lower-concentration patch within the gas flow into which another particle diffuses, only to be captured. At low gas velocities and with smaller particles (0.1µm diameter), this is more common.

Electrostatic:

These filters use large diameter fibre media and rely on electrostatic charges to improve fine particle removal effectiveness.

Impaction due to inertia:

When a particle is too large to respond fast to abrupt changes in streamline direction near a filter fibre, this happens. Because of its inertia, the particle will continue on its original course and collide with the filter fibre. When high gas velocities and dense fibre packing of the filter media are present, this sort of filtration mechanism is most prevalent.

Chronic obstructive pulmonary disease (COPD) is an obstructive, inflammatory lung condition. It encompasses symptoms of emphysema, chronic bronchitis and asthma.

Inhaling high dose steroids are prescribed to treat COPD. They are effective at reducing symptoms and improving lung function. They also work to reduce the number of hospitalisations by decreasing the number of acute exacerbation events. Despite providing effective symptom relief, it cannot slow down the decline of FEV1 as COPD is an irreversible condition.

COPD reduces the FEV1 measurements, as well as the FEV1/FVC ratio.

Breathlessness is a major COPD symptom and can occur at any point in the disease progression, including at an FEV1 >50%.

FEV1 is used in COPD staging, and it is classed as follows:
>80%: Mild or stage I
50 – 79%: Moderate or stage II
30 – 49%: Severe or stage III
<30%: Very severe or stage IV
Patients with mild COPD are usually able to manage their condition on their own, however once the disease progresses to moderate, more GP visits are required, with those in the severe category requiring frequent hospitalisation.

Asthma is correlated to an increase in transfer factor. COPD (emphysema) is correlated to a decreased transfer factor.

COPD predisposes to eventual pulmonary hypertension as a result of an increase in pulmonary vascular resistance.

The SI unit of pressure is the pascal (Pa) and it is equal to one newton (N) per square meter (m2) or N/m2.

1 atmosphere (atm) is the equivalent of:

101325 Pa760 mmHg
1.01325 bar
1033.23 cmH2O.
14.69 pounds per square inch (psi)
1013.25 millibar (mbar) or hectopascals (hPa), and

14.69 psi is equal to one atmosphere. The other values are equal to two atmospheres of pressure.

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

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.

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.

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

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

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

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

Colligative properties are properties of solutions that depend on the number of dissolved particles in solution. They do not depend on the identities of the solutes.

All of the above have colligative properties with the exception of depression of melting point.

The osmolality from the concentration of a substance in a solution is measured by an osmometer. The freezing point of a solution can determines concentration of a solution and this can be measured by using a freezing point osmometer. This is applicable as depression of freezing point is directly correlated to concentration.

Vapour pressure osmometers, which measure vapour pressure, may miss certain volatiles such as CO2, ammonia and alcohol that are in the solution

The use of a freezing point osmometer provides the most accurate and reliable results for the majority of applications.

Colligative properties does not include melting point depression . Mixtures of substances in which the liquid phase components are insoluble, display a melting point depression and a melting range or interval instead of a fixed melting point.

The magnitude of the melting point depression depends on the mixture composition.

The melting point depression is used to determine the purity and identity of compounds. EMLA (eutectic mixture of local anaesthetics) cream is a mixture of lidocaine and prilocaine and is used as a topical local anaesthetic. The melting point of the combined drugs is lower than that individually and is below room temperature (18°C).

The spinous process is the part of a vertebrae that is directed posteriorly.

Typical cervical vertebra have spinous processes that are small and bifid, except for C7, which has a long and prominent spinous process.

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.

An agonist is a molecule with intrinsic efficacy and affinity for a receptor. The ability of a drug-receptor interaction to produce a maximal response is referred to as intrinsic efficacy or activity. Efficacy also refers to a drug’s ability to have a therapeutic or beneficial effect. Although the potencies of morphine and fentanyl differ, they both have the same intrinsic efficacy.

The amount of drug required to produce a given effect is referred to as potency. If drug X is effective in a dose of 100 mcg, its potency is greater than if drug Y is effective in a dose of 10 mg.

The therapeutic index, also known as the margin of safety, is a ratio of the lethal or serious side effect dose of a drug divided by the therapeutic dose of the same drug.

The term bioavailability refers to the ability of a substance to be absorbed. The area under a curve (AUC) of a graphic plot of plasma concentration and time is used to calculate oral bioavailability. It’s used to figure out how much of a drug to take and when to take it.

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.

Pituitary macroadenoma is a benign tumour with growth larger than 10mm (those under 10mm are called microadenoma)

Compression of optic chiasm by pituitary adenoma is responsible for causing visual field defects like bitemporal hemianopia, optic neuropathy.

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 Dopamine 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 less arrhythmogenic than adrenaline

Regarding dopamine part of the dose is converted to Noradrenaline in sympathetic nerve terminals.

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 cyclic adenosine monophosphate).

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 Central nervous system effects.

Dopamine is less arrhythmogenic than adrenaline

Regarding dopamine part of the dose is converted to Noradrenaline in sympathetic nerve terminals.

According to the 2015 National Institute for Health and Care Excellence (NICE) Guidelines, antibiotic prophylaxis against infective endocarditis (IE) is not recommended routinely for people with any cardiac defect (corrected or uncorrected) due to lack of sufficient evidence regarding its benefits. Instead, antibiotic prophylaxis is recommended for those who are at risk of developing IE, such as those with acquired valvular heart disease with stenosis or regurgitation; hypertrophic cardiomyopathy; valve replacement; and previous IE.

The apex of an equilateral triangle completed by the posterior superior iliac spines is where the sacral hiatus or sacrococcygeal membrane can normally located. The failure of posterior fusion of the laminae of the fourth and fifth sacral vertebrae allows the sacral canal to be accessible via the membrane.

In adults, the spine of L4 usually lies on a line drawn between the highest points of the iliac crests (Tuffier’s line). A line connecting each anterior iliac spine, approximates to the L3/4 interspace in the sitting position. Both of these options are incorrect.

A line connecting the greater trochanters is also incorrect.

A line connecting the posterior superior iliac spines is correct, but in adults the presence of a sacral fat pad can still make identification of this landmark less straightforward.

The processes of S5 are remnants only and form the sacral cornua, which are also used to help identify the sacral hiatus.

Ptosis and mydriasis are visible in surgical third nerve palsy, and the eye looks ‘down and out.’ The loss of innervation to all of the major structures supplied by the oculomotor nerve is reflected in these characteristics.

Ptosis is caused by the paralysis of the levator palpebrae superioris in oculomotor nerve palsy. Due to the unopposed actions of the superior oblique and lateral rectus muscles, the eye rotates down and out.

Mydriasis is caused by surgical (compressive) causes of third nerve palsy, which disrupt the parasympathetic pupillomotor fibres on the nerve’s periphery.

Medical (ischaemic) causes of a third nerve palsy, on the other hand, leave the superficial parasympathetic fibres relatively unaffected and the pupil unaffected.

Horner’s syndrome is characterised by ptosis, anhidrosis, and miosis, which are caused by a loss of sympathetic innervation to the tarsal muscle of the upper lid, facial skin, and dilator pupillae, respectively.

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

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

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

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

The commonest and most likely cause of a gradual rise in end-tidal CO2 (EtCO2) occurring during anaesthesia in a spontaneously breathing patient is hypoventilation. This occurs from the respiratory depressant effects of the opioid and sevoflurane.

Malignant hyperthermia should be sought if the EtCO2 shows further progressive rise.

Causes of rebreathing and a rise in the baseline of the capnograph can be caused by exhausted soda lime and inadequate fresh gas flow into the Bain circuit.

A sudden rise in EtCO2 can be caused deflation of the tourniquet.

The principle by which a strain gauge works is that when a wire is stretched, it becomes longer and thinner, and as a result, its resistance increases.

A strain gauge, which is used in pressure transducers, acts as a resistor. When the pressure in a pressure transducer changes, the diaphragm moves, changing the tension in the resistance wire and thus changing the resistance.

Changes in current flow through the resistor are amplified and displayed as a pressure change measure.

A Wheatstone bridge, on the other hand, is frequently used to measure or monitor these changes in resistance.

Tranylcypromine is a monoamine oxidase inhibitor that binds irreversibly to target enzyme.

Monoamine oxidase inhibitors are responsible for blocking the monoamine oxidase enzyme. The monoamine oxidase enzyme breaks down different types of neurotransmitters from the brain: norepinephrine, serotonin, dopamine, and tyramine. MAOIs inhibit the breakdown of these neurotransmitters thus, increasing their levels and allowing them to continue to influence the cells that have been affected by depression.

There are two types of monoamine oxidase, A and B. The MAO A is mostly distributed in the placenta, gut, and liver, but MAO B is present in the brain, liver, and platelets. Serotonin and noradrenaline are substrates of MAO A, but phenylethylamine, methylhistamine, and tryptamine are substrates of MAO B. Dopamine and tyramine are metabolized by both MAO A and B. Selegiline and rasagiline are irreversible and selective inhibitors of MAO type B, but safinamide is a reversible and selective MAO B inhibitor.

MAOIs prevent the breakdown of tyramine found in the body and certain foods, drinks, and other medications. Patients that take MAOIs and consume tyramine-containing foods or drinks will exhibit high serum tyramine level. A high level of tyramine can cause a sudden increase in blood pressure, called the tyramine pressor response. Even though it is rare, a high tyramine level can trigger a cerebral haemorrhage, which can even result in death.

Eating foods with high tyramine can trigger a reaction that can have serious consequences. Patients should know that tyramine can increase with the aging of food; they should be encouraged to have fresh foods instead of leftovers or food prepared hours earlier. Examples of high levels of tyramine in food are types of fish and types of meat, including sausage, turkey, liver, and salami. Also, certain fruits can contain tyramine, like overripe fruits, avocados, bananas, raisins, or figs. Further examples are cheeses, alcohol, and fava beans; all of these should be avoided even after two weeks of stopping MAOIs. Anyone taking MAOIs is at risk for an adverse hypertensive reaction, with accompanying morbidity. Patients taking reversible MAOIs have fewer dietary restrictions.

Amitriptyline is a tricyclic antidepressant, and citalopram and escitalopram are selective serotonin reuptake inhibitors.

When a drug is given via intravenous infusion, the plasma concentration rises exponentially as a wash-in curve until it reaches steady-state concentration (the point at which the infusion rate is balanced by the elimination rate or clearance). To reach this steady state, the drug will take 4-5 half-lives.

Cpss (target plasma concentration at steady state) and clearance (CL) in ml/minute or litre/hour are the two factors that determine the infusion rate or dose (ID) in mg/hour of a drug.

ID = Cpss × CL

We know the infusion rate is 20 ml/hour in this case. The drug’s concentration is 5 mg/mL. The patient is receiving 100 mg of the drug per hour, with a 20 L/hour clearance rate.

ID = Cpss × 20

Therefore,

Cpss = 100 mg/20000 ml

Cpss = 0.005 mg/mL or 5 mcg/mL

Haemorrhage, including intracranial bleeding, is a common and potentially fatal side effect of warfarin therapy, and reversing anticoagulation quickly and completely can save lives. When complete and immediate correction of the coagulation defect is required in orally anticoagulated patients with life-threatening haemorrhage, clotting factor concentrates are the only viable option.

For rapid reversal of vitamin K anticoagulants, prothrombin complex concentrates (PCC) are recommended. They contain the vitamin K-dependent clotting factors II, VII, IX, and X and are derived from human plasma. They can be used as an adjunctive therapy in patients with major bleeding because they normalise vitamin K dependent clotting factors and restore haemostasis.

The most common treatments are fresh frozen plasma (FFP) and vitamin K. The efficacy of this approach is questioned due to the variable content of vitamin K-dependent clotting factors in FFP and the effects of dilution. Significant intravascular volume challenge, as well as the possibility of rare complications like transfusion-associated lung injury or blood-borne infection, are all potential issues.

To avoid anaphylactic reactions, vitamin K should be given as a slow intravenous infusion over 30 minutes. Regardless of the route of administration, the reversal of INRs with vitamin K can take up to 24 hours to reach its maximum effect.

Reversal of anticoagulation in patients with warfarin-associated intracranial haemorrhage may be considered with factor VIIa (recombinant), but its use is controversial. There are concerns about thromboembolic events following treatment, as well as questions about assessing efficacy in changes in the INR. If the drug is to be administered, patients should be screened for an increased risk of thrombosis before the drug is given.

Nitric oxide (NO), an endothelial-derived relaxant factor (EDRF), is a powerful vasodilator. Its cell-signalling molecule is calcium-dependant and generated endogenous by nitric oxide synthetases from the precursor L-arginine, oxygen and NADPH. Three main isoforms have been isolated and they are inducible (iNO), neuronal (nNO) and endothelial (eNO).

Endothelial NO stimulates intracellular guanylyl cyclase which generates cyclic GMP (cGMP) from its action on guanylyl tri-phosphate (GTP). The cGMP goes on to activate protein kinase G (PKG). PKG phosphorylates cell membrane proteins that regulate intracellular calcium concentrations and level of calcium sensitisation.

Smooth muscle vasodilatation results from:

1. Light chain phosphatase activation.
2. Inhibition of calcium entry into the cell (reducing Ca2+ concentrations) and
3. Hyperpolarisation of cells by activation of H+ channels.

It is well known that atropine will cross the placenta and that maternal administration results in an increase in fetal heart rate.

Atropine is highly selective for muscarinic receptors. Its potency at nicotinic receptors is much lower, and actions at non-muscarinic receptors are generally undetectable clinically. Atropine does not distinguish among the M1, M2, and M3 subgroups of muscarinic receptors. In contrast, other antimuscarinic drugs are moderately selective for one or another of these subgroups. Most synthetic antimuscarinic drugs are considerably less selective than atropine in interactions with nonmuscarinic receptors.

A study on glycopyrrolate, a quaternary ammonium salt, was found to have a fetal: maternal serum concentration ratio of 0.4 indicating partial transfer.

Heparin, suxamethonium, and vecuronium do not cross the placenta.

The trochlear nerve (CN IV) is the fourth and smallest cranial nerve. It’s role is to provide somatic motor innervation of the superior oblique muscle which is responsible for oculomotion.

Injury to the trochlear nerve will result in vertical diplopia, which worsens when looking downwards or inwards. This diplopia presents as an upward deviation of the eye with a head tilt away from the site of the lesion.

The abducens nerve (CN VI) provides somatic motor innervation for the lateral rectus muscle which functions to abduct the eye. Injury to this nerve will cause diplopia and an inability to abduct the eye, causing the patient to have to rotate their head to look sideways.

The facial nerve (CN VII) provides sensory, motor and parasympathetic innervations. It’s motor aspect controls the muscles of facial expression. Damage will cause paralysis of facial expression.

The oculomotor nerve (CN III) provides motor and parasympathetic innervations. Its motor component controls most of the other extraocular muscles. Damage to it will result in ptosis, dilatation of the pupil and a down and out eye position.

The ophthalmic division of the trigeminal nerve (CN VI) is responsible for sensory innervation of skin, mucous membranes and sinuses of the upper face and scalp.

Interleukin-4 is a cytokine which acts to regulate the responses of B and T cells.

Erythropoietin is responsible for the signal that initiated red blood cell production.

Granulocyte-colony stimulating factor stimulates the bone marrow to produce granulocytes.

Interleukin-5 is a cytokine that stimulates the proliferation and activation of eosinophils.

Thrombopoietin is the primary signal responsible for megakaryocyte and thus platelet production.
Platelets are also called thrombocytes. They, like red blood cells, are also derived from myeloid stem cells. The process involves a megakaryocyte developing from a common myeloid progenitor cell. A megakaryocyte is a large cell with a multilobulated nucleus, this grows to become massive where it will then break up to form platelets.

Immune cells are generated from haematopoietic stem cells in bone marrow. They generate two main types of progenitors, myeloid and lymphoid progenitor cells, from which all immune cells are derived.

When there is capillary leakage as seen in dependent oedema or ascites, oncotic pressure becomes a problem.

The intracellular sodium concentration is very sensitive to the extracellular sodium concentrations. When there is an imbalance, osmosis occurs resulting in shifts in water between the two compartments.

The microvascular endothelium relies upon osmosis and other processes as it is not freely permeable to water.

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.

Number needed to harm are a measure of the impact of a treatment or intervention that is often used to communicate results to patients, clinicians, the public and policymakers. It states how many patients need to be treated for one additional patient to experience an adverse outcome (e.g. a death). It is calculated as the inverse of the absolute risk reduction. It can equally well be applied to harmful outcomes as well as beneficial ones, where it becomes numbers needed to treat (NNT) instead.

In this way, they are both calculated the same but NNT usually refers to a therapeutic treatment whereas NNH refers to a risk-factor for disease.

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

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

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

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

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

A decrease in the functional residual capacity (FRC) is the most important physiologic change to consider for such patients.

FRC is the sum of the expiratory reserve volume and the residual volume. It is the resting volume of the lung, and is an important marker for lung function. During this time, the alveolar pressure is equal to the atmospheric pressure. When morbidly obese individuals lie supine, the FRC decreases by as much as 40% because the abdominal contents push the diaphragm into the thoracic cavity.

Chest wall compliance is expected to reduce because of fat deposition surrounding adjacent structures.

Inspiratory reserve volume (IRV) is expected to increase, and peak expiratory flow is expected to decrease, however the decrease in FRC is more important to consider because of the risk of hypoxia secondary to premature airway closure and ventilation-perfusion mismatch.

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

Second messengers relay signals to target molecules in the cytoplasm or nucleus when an agonist interacts with a receptor on the cell surface. They also amplify the strength of the signal. The most ubiquitous and abundant second messenger is calcium and it regulates multiple cellular functions in the body.

These include:
Muscle contraction (skeletal, smooth and cardiac)
Exocytosis (neurotransmitter release at synapses and insulin secretion)
Apoptosis
Cell adhesion to the extracellular matrix
Lymphocyte activation
Biochemical changes mediated by protein kinase C.

cAMP is either inhibited or stimulated by G proteins.

The receptors in the body that stimulate G proteins and increase cAMP include:

Beta (?1, ?2, and ?3)
Dopamine (D1 and D5)
Histamine (H2)
Glucagon
Vasopressin (V2).

The second messenger for the action of nitric oxide (NO) and atrial natriuretic peptide (ANP) is cGMP.

The second messengers for angiotensin and thyroid stimulating hormone are inositol triphosphate (IP3) and diacylglycerol (DAG).

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

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

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

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

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.

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

External carotid artery originates at the upper border of the thyroid cartilage. It ascends and lies anterior to the internal carotid arteries and posterior to the posterior belly of the digastric muscle and stylohyoid muscle.

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

Ketamine is the substance in question. Its structure and pharmacodynamic effects make it a one-of-a-kind intravenous induction agent. The molecule is made up of two cyclohexanone rings (2-(O-chlorophenyl)-2-methylamino cyclohexanone and 2-(O-chlorophenyl)-2-methylamino cyclohexanone). Ketamine has local anaesthetic properties and acts primarily on the brain and spinal cord.

It affects Ca2+ channels as a non-competitive antagonist for the N-D-methyl-aspartate (NMDA) receptor. It also acts as a local anaesthetic by interfering with neuronal Na+ channels.

Ketamine causes profound dissociative anaesthesia (profound amnesia and analgesia) as well as sedation.

Phenoxybenzamine, an alpha-1 adrenoreceptor antagonist, is an example of an irreversible competitive antagonist. It forms a covalent bond with the calcium influx receptor.

Benzodiazepines are GABAA receptor agonists that affect chloride influx.

Flumazenil is an inverse agonist that affects GABAA receptor chloride influx.

Ketamine is a cyclohexanone derivative that acts as a non-competitive Ca2+ channel antagonist.

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

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

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

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

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

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.

The lesser omentum will need to be divided. This forms one of the nodal stations that will need to be taken during a radical gastrectomy.

The celiac axis is the first branch of the abdominal aorta and supplies the entire foregut (mouth to the major duodenal papilla). It arises at the level of vertebra T12. It has three major branches:
1. Left gastric
2. Common hepatic
3. Splenic arteries

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.

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.

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

Other BChE phenotypes are the following:

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

The metabolism of drugs in the liver occurs in 3 phases

Phase I: This involves functionalization reactions, which are of 3 types, namely hydrolysis, oxidation and reduction reactions catalysed by the cytochrome P450 (CYP) enzymes.

Phase II: This involves conjugation or acetylation reactions. The goal is to create water soluble metabolites that can be excreted from the body.

The liver is the second largest organ. It’s smallest functional unit is the acinus which is divided into 3 zones:

Zone I (periportal): This zone receives the largest amount of oxygen supply as it is the closest to the blood vessels. It is the site of plasma protein synthesis.

Zone II (mediolobular): This is located between the portal triad and central vein.

Zone III (centrilobular): This is closest to the central vein and receives the least amount of oxygen supply.

Kupffer cells are specialized macrophages found in the periportal zone of the liver, and function to remove foreign particles and breakdown red blood cells via phagocytosis.

Ito cells are fat-storing liver cells found in the space of Disse. Their function is to take-uo, store and secrete retinoids, as well as manufacture and release proteins that make up the extracellular matrix.

Sensory innervation of the larynx is controlled by branches of the vagus nerve.

The internal and external bifurcations of the superior laryngeal nerve is responsible for sensory innervation of the aspect of the larynx superior to the vocal cords, while the recurrent laryngeal nerve is responsible for sensory innervation of the intrinsic musculature of the larynx except for the cricothyroid muscle.

Understanding of the cardiac action potential helps with the understanding of the ECG which measures the electrical activity of the heart. This is reflected in its waveform.
The rapid depolarisation phase is reflected in the QRS complex. After this phase comes the plateau phase which is represented by the ST segment. Lastly, the T wave shows repolarisation, phase 3.

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. (ST segment)

Phase 3 – Final repolarisation – caused by an efflux of potassium. (T wave)

Phase 4 – Restoration of ionic concentrations – The resting potential is restored by Na+/K+ATPase.
There is slow entry of Na+into the cell which decreases the potential difference until the threshold potential is reached. This then triggers a new action potential

Of note, cardiac muscle remains contracted 10-15 times longer than skeletal muscle.

Different sites have different conduction velocities:
1. Atrial conduction – Spreads along ordinary atrial myocardial fibres at 1 m/sec

2. AV node conduction – 0.05 m/sec

3. Ventricular conduction – Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec, the fastest conduction in the heart. This allows a rapid and coordinated contraction of the ventricles

The AAGBI and the British Hypertension Society has published guidelines for the measurement of adult blood pressure and management of hypertension before elective surgery.

The objective is to ensure that patients admitted for elective surgery have a known systolic blood pressure below 160 mmHg and diastolic blood pressures below 100 mmHg. The primary health care teams, if possible, should ensure that this is the case and provide evidence to the pre-assessment clinic staff or on admission.

Avoiding cancellation on the day of surgery because of white coat hypertension is a secondary objective.

Patients with blood pressures below 180 mmHg systolic and 110 mmHg diastolic (measured in the preop assessment clinic), who present to pre-operative assessment clinics without documented evidence of primary care blood pressures should proceed to elective surgery.

In this question, the history/assessment does not appear to point to obvious end-organ damage so there is no indication for further investigation for secondary causes of hypertension or an echocardiogram at this point. Further review and treatment at this point is not required.

However, you should write to the patient’s GP and encourage serial blood pressure measurements in the primary health care setting.

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

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

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

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

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

Propofol is a short-acting medication used for starting and maintenance of general anaesthesia, sedation for mechanically ventilated adults, and procedural sedation.
The dose of propofol is 1-2 mg/kg.

Dose of some other important drugs are listed below:
Thiopental dose: 3-7 mg/kg
Ketamine dose: 1-2 mg/kg
Etomidate dose: 0.3 mg/kg
Methohexitone dose: 1.0-1.5 mg/kg

Hypochondriasis is an illness anxiety disorder, and describes excessively worriedness about the presence of a disease. While the woman is concerned about her possibility of developing motor neurone disease, she understands that no symptoms have yet appeared. Hypochondriasis involves patients who refuse to accept that they don’t have the disease, even if the results come back negative.

Late Look Bias occurs when the data is gathered or analysed at an inappropriate time e.g. when many of the subjects suffering from a fatal disease have died. This type of biasness might occur in some retrospective studies of motor neurone disease, but is not applicable to this prospective study.

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. Of all the options, lead time-bias is a better answer.

The Hawthorne Effect refers to groups modifying their behaviour simply because they are aware of being observed. Any differences in the behaviour have not been mentioned in the question, and it is highly unlikely that a change in patient’s behaviour would have affected their length of survival in this case.

The correct option is lead-time bias. Even if the new blood test diagnoses the disease earlier, it doesn’t affect the outcome, as the survival time was still on average 43 months from the onset of symptoms in both groups. With the help of blood test, the disease was only detected 8 months earlier.

During carotid endarterectomy, injury to the vagus nerve or its branches can cause hoarseness. Injury to the vagus nerve can result in adductor vocal cord paralysis. It can also cause other symptoms like dysphagia or even vocal cord immobility.

Carotid endarterectomy is the procedure to relieve an obstruction in the carotid artery by opening the artery at its origin and stripping off the atherosclerotic plaque with the intima. Because of the internal carotid artery relations, there is a risk of cranial nerve injury during the procedure involving one or more of the following nerves: CN IX, CN X (or its branch, the superior laryngeal nerve), CN XI, or CN XII.

However, only damage to the vagus would account for speech difficulties.

Nitric oxide is generated from L-arginine by nitric oxide synthase. It is produced in response to haemodynamic stress by the vascular endothelium, and it produces both smooth muscle relaxation and reduced vascular resistance.

Nitric oxide may be inactivated through interaction with other oxygen free radicals, (e.g. oxidised low-density lipoprotein (LDL)).

Nitric oxide causes the production of the second messenger, cyclic guanosine monophosphate (cGMP).

Porphyria is a group of disorders in which there is excess production and excess excretion of porphyrins and their precursors. They are usually genetic and are caused due to defects in the haem metabolic pathway. However, other factors like infection, pregnancy, mensuration, starvation may precipitate the attack.

Sulphonamides, barbiturates (methohexitone and thiopental), and phenytoin are considered to be precipitants so are not safe to use
Chloral hydrate is thought to be safe to use.
Etomidate lacks proper studies and may be used with caution but it is generally advised not to use this drug especially if other alternatives are available.

The bifurcation of the abdominal aorta into common iliac arteries occurs at the level of L4. The bifurcation is a common site for atherosclerotic plaques as it is an area of high turbulence.

Leriche Syndrome is an aortoiliac occlusive disease and affects the distal abdominal aorta, iliac arteries, and femoropopliteal vessels. It has a triad of symptoms:
1. Claudication (cramping lower extremities pain that is reproducible by exercise)
2. Impotence (reduced penile arterial flow)
3. Absent/weak femoral pulses (hallmark)

T12 – aorta enters the diaphragm with the thoracic duct and azygous veins

L2 – testicular or ovarian arteries branch off the aorta

L3 – inferior mesenteric artery

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

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

The cephalic vein is one of the primary superficial veins of the upper limb. It overlies most of the fascial planes as it is located in the superficial fascia along the anterolateral surface of the biceps.

It originates in the anatomical snuffbox from the radial side of the superficial venous network of the dorsum of the hand. It travels laterally up the arm to join the basilic vein via the median cubital vein at the elbow.

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

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.

Cell membrane pore formation, Bacterial DNA damage, Peptidoglycan cross-linking inhibition, and peptidoglycan synthesis inhibitor are always lethal and such mechanisms are possible only in bactericidal drugs. But Protein synthesis inhibition would only prevent cell replication or cell growth and is responsible for bacteriostatic effects of the drug.

In statistical terms, correlation is used to denote association between two quantitative variables.

The degree of association is measured by a correlation coefficient, denoted by r. The correlation coefficient is measured on a scale that varies from + 1 through 0 to – 1. Complete correlation between two variables is expressed by either + 1 or -1. When one variable increases as the other increases the correlation is positive; when one decreases as the other increases it is negative. Complete absence of correlation is represented by 0.

The two methods are not synonymous as correlation measures the degree of relationship between two variables whereas regression analysis is about how one variable affects another or what changes it has on the other variable. Both are also shown by a different graphical representation.

Normally, the oesophagus is lined by non-keratinized stratified squamous epithelium. This epithelium can undergo metaplasia and convert to the columnar epithelium (stomach’s lining) in long-standing GERD that leads to Barret’s oesophagus.

The basal metabolic rate (BMR) is the amount of energy required to maintain basic bodily functions in the resting state. The unit is Watt (Joule/second) or calories per unit time.

Indirect calorimetry measures O2 consumption and CO2 production where gases are collected in a canopy which is the gold standard, Douglas bag, face-mask dilution technique or interfaced with a ventilator.

The BMR can be calculated using the Weir formula:

Metabolic rate (kcal per day) = 1.44 (3.94 VO2 + 1.11 VCO2)

The BMR should be measured while lying down and at rest with the following conditions met:

It should follow a 12 -hour fast
No stimulants ingested within a 12-hour period
It should be done in a neutral thermal environment (between 20°C-25°C)

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

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

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

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

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

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

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

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

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

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

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

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

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

This patient is morbidly obese and has a high risk of developing hypoxia. This will be exacerbated by the patient’s supine position, as a result of:

Functional residual capacity has been reduced (FRC)
Increased closing capacity (CC)
Reduced tidal volume due to increased airway resistance, decreased thoracic cage compliance, and decreased respiratory muscle strength and endurance
Following induction of general anaesthesia, there is a tendency for atelectasis and increased O2 consumption due to the increased workload of respiratory muscles and the overall increase in metabolism.

Pre-oxygenation with 100 percent oxygen via a tight-fitting mask can be done using either tidal volume breaths for three to five minutes or four vital capacity breaths in normal circumstances. In the head-up position, this patient is much more likely to be adequately pre-oxygenated, maximising the FRC and minimising the CC. In spontaneously breathing patients, the Mapleson A and circle systems are both effective, but the Mapleson D requires 160-200 ml/kg/minute to prevent rebreathing.

Aldosterone is produced in the zona glomerulosa of the adrenal cortex and acts to increase sodium reabsorption via intracellular mineralocorticoid receptors in the distal tubules and collecting ducts of the nephron.

Its release is stimulated by hypovolaemia, blood loss ,and low plasma sodium and is inhibited by hypertension and increased sodium. It is regulated by the renin-angiotensin system.

The structures that pass through the foramen magnum are:

Meningeal lymphatics
Spinal cord
Spinal meninges
Sympathetic plexus of vertebral arteries
Vertebral arteries
Vertebral artery spinal branches
The spinal roots of the accessory nerve.

The jugular foramen contains the vagus nerve, the accessory nerve and glossopharyngeal nerve.

The vertebral veins does not pass into the skull.

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

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

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

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

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.

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.

An abdominal aortic aneurysm is a swelling in the abdominal aorta. It most commonly occurs in men over 65 years old of age. Smoking, diabetes, hypertension, and hypercholesterolemia are other risk factors contributing to the disease.

The NHS screening program for abdominal aortic aneurysms involves an ultrasound test for men aged 65 or over if they have not undergone screening for a one-off screening test.

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

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

Sodium is a primarily extracellular ion.

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

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

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

Platelets are fragments of megakaryocytes and they are encapsulated by membrane.

They have no nucleus but are metabolically active and are able to express membrane receptors and release stored substances when triggered. adenosine diphosphate and serotonin are 2 of its content.

Because they have no nucleus, they are not able to produce new proteins. This is why aspirin and other drugs affect function for their entire lifespan after exposure. Its lifespan is approximately 9-10 days in normal individuals.

Platelets does NOT PRODUCE prostacyclin but are able to produce nitric oxide, prostaglandins and thromboxane.

Paediatric life support differs from adult life support in that hypoxia is the primary cause of deterioration.

After checking for danger, the child should be given a gentle stimulus (such as holding the head and shaking the arm) and asked, Are you alright? according to current advanced paediatric life support (APLS) guidelines. Safety, Stimulate, Shout is a phrase that is frequently remembered. Any airway assessment should be preceded by these actions.

Although the algorithm includes five rescue breaths, they are performed after the airway assessment.

It is not recommended to ask parents to leave unless they are obstructing the resuscitation. A team member should be with them at all times to explain what is going on and answer any questions they may have.

CPR should not begin until the child has been properly assessed and rescue breaths have been administered.

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.

Alpha 1 adrenergic receptor stimulation results in vasoconstriction of peripheral arteries mainly of those of skin, gut and kidney arterioles. This would cause and increase in total peripheral resistance and mean arterial pressure and as a result the perfusion of vital organs i.e. brain, heart and lungs are maintained.

Muscarinic M2 receptor also known as cholinergic receptor are located in heart, where they act to slow the heart rate down to normal sinus rhythm after negative stimulatory actions of parasympathetic nervous system. They also reduce contractile forces of the atrial cardiac muscle, and reduce conduction velocity of AV node. This could worsen the compensation.

Stimulation of beta 2 adrenergic receptor result in dilation of smooth muscle as in bronchodilation.

Beta 3 adrenergic receptors are present on cell surface f both white and brown adipocytes and are responsible for lipolysis, thermogenesis, and relaxation of intestinal smooth muscle.

Alpha 2 adrenergic receptor stimulation results in inhibition of the release of noradrenaline in a form of negative feedback.

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

The zones from proximal to distal are:

Trachea
Bronchi
Bronchioles
Terminal bronchioles
Respiratory bronchioles
Alveolar ducts
Alveolar sacs

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

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

There are different models of flowmeters determined by the applied pressure and its orifice. For instance, the watersight flowmeter functions through applying variable pressure, and it has a variable orifice. In contrast, the bubble flowmeter is operated using a constant pressure and orifice. Flowmeters such as rotameters, Heidbrink and Peak have a constant pressure but variable orifice. On the other hand, flowmeters including a simple pressure gauge, water depression, and pneumotachograph have a constant orifice but variable pressure.

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

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

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

Hepatotoxicity due to halothane administration is relatively common and is a major factor in its rapidly declining use. Type 1 hepatotoxicity has an incidence of 20% to 30%. A comprehensive report in 1969 demonstrated an incidence of type 2 hepatotoxicity (hepatitis) of 1 case per 6000 to 20000 cases, with fatal cases occurring approximately once in 35000 patients following a single exposure to the anaesthetic. This incidence of fatal cases increases to approximately 1 in 1000 patients following multiple exposures. Following this study was a large-scale review in the United Kingdom, which showed similar results. To put this into perspective, there is only a single case of hepatotoxicity confirmed after the administration of desflurane and 2 cases per 1 million after enflurane. By the 1970s, halothane was the most common cause of drug-induced liver failure.

Halothane-induced hepatotoxicity has a female to male ratio of two to one. Younger patients are less likely to be affected; 80% of the cases are typically in patients 40 years or older. Other risk factors include obesity and underlying liver dysfunction. Medications such as phenobarbital, alcohol, and isoniazid may play a role in affecting CYP2E1 metabolism, increasing one’s risk.

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

For estimating a child’s weight, the Resuscitation Council (UK) and European Resuscitation Council teach the following formula:

Weight = (age + 4) × 2

The weight of the child will be around 20 kg.

This formula is used in the Primary FRCA exam by the Royal College of Anaesthetists.

In ‘developed’ countries, the traditional ‘APLS formula’ for estimating weight in children based on age (wt in kg = [age+4] x 2) is acknowledged as underestimating weight by 33.4 percent on average, with the degree of underestimation increasing with increasing age.

However, more recently, the APLS formula ‘Weight=3(age)+7’ has been found to provide a mean underestimate of only 6.9%. This formula is applicable to children aged 1 to 13 years.

The estimated weight based on age using this formula is 25 kg.

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

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

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

The common peroneal (fibular) nerve is a peripheral nerve in the lower limb. It arises of the L4-S2 nerve roots and has sensory and motor innervations:

Sensory: Provides innervation of the lateral leg and foot dorsum.

Motor: Provides innervation of the short head of the biceps femoris, as well as muscles of the anterior and lateral leg compartments.

It is the most commonly damaged nerve in the lower extremity, as it is easily compressed by a plaster cast or injured when the fibula is fractured.

Damage to the common peroneal nerve will result in loss of dorsiflexion at ankle (footdrop, as feet are permanently plantarflexed), with the accompanying high stepping gait.

The saphenous and sural nerve only provide sensory innervation.

The tibial nerve arises from the sciatic nerve (like the common peroneal), but it provides motor innervation to the posterior leg compartments and intrinsic foot muscles. Injury to the tibial nerve will cause loss of plantar flexion, toe flexion and weakened foot inversion.

Extreme hip flexion into the lithotomy or Lloyd-Davies position can result in stretch damage to the neurones (sciatic and obturator nerves) or by applying direct pressure (femoral nerve compression).