Warfarin prevents reductive metabolism of the inactive vitamin K epoxide back to its active hydroquinone form. Thus, warfarin inhibits the synthesis of vitamin K dependent clotting factors: X, IX, VII, II (prothrombin), and of the anticoagulants protein C and protein S. The therapeutic range for oral anticoagulant therapy is defined in terms of an international normalized ratio (INR). The INR is the prothrombin time ratio (patient prothrombin time/mean of normal prothrombin time for lab)ISI, where the ISI exponent refers to the International Sensitivity Index and is dependent on the specific reagents and instruments used for the determination. A prolonged INR is widely used as an indication of integrity of the coagulation system in liver disease and other disorders, it has been validated only in patients in steady state on chronic warfarin therapy.

Prothrombin complex concentrate (PCC) is used to replace congenital or acquired vitamin-K deficiency warfarin-induced anticoagulant effect, particularly in the emergent setting.

Intravenous vitamin K has a slower onset of action compared to PCC, but is useful for long term therapy.

Fresh frozen plasma (FFP) prepared from freshly donated blood is the usual source of the vitamin K-dependent factors and is the only source of factor V. The factors needed, however, are found in small quantities compared to PCC.

Cryoprecipitate is indicated for hypofibrinogenemia/dysfibrinogenemia, von Willebrand disease, haemophilia A, factor XIII deficiency, and management of bleeding related to thrombolytic therapy.

Charles’ Law states that there is a direct correlation between temperature and volume, where pressure and amount gas are constant. As temperature increases, volume also increases.

Boyle’s Law states that Pressure is inversely proportional to volume, assuming that temperature and amount of gas are constant. As volume increases, pressure decreases. In Dalton’s law of partial pressure, the total pressure exerted by a mixture of gases is equal to the sum of the partial pressure of the gases in mixture.

According to Henry’s Law for concentration of dissolved gases, at a constant temperature, the amount of a given gas that dissolves in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid. An equivalent way of stating the law is that the solubility of a gas in a liquid is directly proportional to the partial pressure of the gas above the liquid.

Gay-Lussac’s Law states that the pressure of a given mass of gas varies directly with the absolute temperature of the gas, when the volume is kept constant. This law is very similar to Charles’ Law, with the only difference being the type of container. Whereas the container in a Charles’ Law experiment is flexible, it is rigid in a Gay-Lussac’s Law experiment.

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.

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

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

Observation bias occurs when the behaviour of an individual changes that results from their awareness of being observed.

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

Attrition bias is a systematic error caused by unequal loss of participants from a randomized controlled trial (RCT). In clinical trials, participants might dropout due to unsatisfactory treatment or efficacy, intolerable adverse events, or even death.

Selection bias introduced when the individuals are not chosen randomly to take a part in the study. It usually occurs when the research decides who is going to be studied, they are not the representative of the population.

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

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

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.

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

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

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

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.

The patient is rebreathing carbon dioxide that has been exhaled.

Exhaustion of the soda lime and failure of the expiratory valve are the two most likely causes. A leak in the inspiratory limb is a less likely cause. Increased inhaled and exhaled carbon dioxide levels may appear with a normal-looking capnogram if the expiratory valve is ineffective.

The patient will exhale into both the inspiratory and expiratory limbs if the inspiratory valve is inoperable. A slanted downstroke inspiratory phase (as the patient inhales carbon dioxide-containing gas from the inspiratory limb) and increased end-tidal carbon dioxide can be seen on the capnogram.

Even if the soda lime were exhausted, a high fresh gas flow would be enough to prevent rebreathing. The difference in oxygen concentrations in inspired and expired breaths would be less pronounced.

Hypercapnia is caused by respiratory obstruction and malignant hyperthermia, but not by rebreathing.

pH is the negative log to the base 10 of hydrogen ion concentration:

So, what power produces the answer?

pH = – log10 [H+]

Making [H+] the subject:

[H+] = 10-pH

Substituting, [H+] = 10-7

One nanomole = 1 x 10-9 or 0.000000001

10-7 = 1x 0.0000001 or 10 x 0.00000001 or 100 x 0.000000001

100 nanomole

There are different classes of electrical equipment that can be classified in the table below:

Class 1 – provides basic protection only. It must be connected to earth and insulated from the mains supply

Class II – provides double insulation for all equipment. It does not require an earth.

Class III – uses safety extra low voltage (SELV) which does not exceed 24 V AC. There is no risk of gross electrocution but risk of microshock exists.

Type B – All of above with low leakage currents (0.5mA for Class IB, 0.1 mA for Class IIB)

Type BF – Same as with other equipment but has ‘floating circuit’ which means that the equipment applied to patient is isolated from all its other parts.

Type CF – Class I or II equipment with ‘floating circuits’ that is considered to be safe for direct connection with the heart. There are extremely low leakage currents (0.05mA for Class I CF and 0.01mA for Class II CF)

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

The relative risk (also known as risk ratio [RR]) is the ratio of risk of an event in one group (e.g., exposed group) versus the risk of the event in the other group (e.g., nonexposed group).

The odds ratio (OR) is the ratio of odds of an event in one group versus the odds of the event in the other group.

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

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

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

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 question mentions a quantitative, ratio scale data set. The use of mean would be ideal under normal circumstances, however, in this situation median is preferred as it is less sensitive to the skewness of data. The median is usually preferred to other measures of central tendency when your data set is skewed (i.e., forms a skewed distribution)

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 blood vessel well is divided into 3 parts, namely:

The tunica intima, which is the deepest layer. It contains endothelial cells separated by gap junctions

The tunica media, primarily consisting of the involuntary smooth muscle fibres, laid out in spiral layers with elastic fibres and connective tissue.

The tunica adventitia, which is the most superficial layer. It consists of the vasa vasorum, fibroblast and collagen.

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

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

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

In contrast to the arterial system, which contains 15% of the circulating blood volume, the body’s veins contain 70% of it.

In severe haemorrhage, when sympathetic stimulation causes venoconstriction, venous tone is important in maintaining the return of blood to the heart.

Because the liver receives about 30% of the resting cardiac output, it is a very vascular organ. The hepatic vascular system is dynamic, which means it can store and release blood in large amounts – it acts as a reservoir within the general circulation.

In a normal situation, the liver contains 10-15% of total blood volume, with the sinusoids accounting for roughly 60% of that. The liver dynamically adjusts its blood volume when blood is lost and can eject enough blood to compensate for a moderate amount of haemorrhage.

In the portal venous and hepatic arterial systems, sympathetic nerves constrict the presinusoidal resistance vessels. More importantly, sympathetic stimulation lowers the portal system’s capacitance, allowing blood to flow more efficiently to the heart.

Net transcapillary absorption of interstitial fluid from skeletal muscle into the intravascular space compensates for blood loss effectively during haemorrhage. The decrease in capillary hydrostatic pressure (Pc), caused by reflex adrenergic readjustment of the ratio of pre- to postcapillary resistance, is primarily responsible for fluid absorption. Within a few hours of blood loss, these fluid shifts become significant, further diluting haemoglobin and plasma proteins.

Albumin synthesis begins to increase after 48 hours.

The juxtamedullary complex releases renin in response to a drop in mean arterial pressure, which causes an increase in aldosterone level and, eventually, sodium and water resorption. Increased antidiuretic hormone (ADH) levels also contribute to water retention.

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

RQ = CO2 eliminated/O2 consumed

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

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

The RQ for carbohydrates is = 1.0

The RQ for the rest of the compounds are:

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

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

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.

Cardiac conduction

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

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

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

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

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

The most likely of the differential diagnosis in this case is a duodenal ulcer located on the posterior abdominal wall.

These can cause an erosion of the abdominal wall, eventually affecting the gastroduodenal artery and resulting in major bleeding and haematemesis.

Gastroduodenal artery supplies the pylorus, proximal part of the duodenum, and indirectly to the pancreatic head (via the anterior and posterior superior pancreaticoduodenal arteries)

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.

The epiploic foramen (foramen of Winslow or aditus to the lesser sac) is found behind the free right border of the lesser omentum. A short, 3 cm slit serves as the entrance to the lesser sac from the greater sac.

The epiploic foramen has the following boundaries:
Anteriorly: hepatoduodenal ligament, the bile duct (anteriorly on the right), the hepatic artery (anteriorly on the left), and the portal vein (posteriorly) together with nerves and lymphatics
Superiorly: the peritoneum of the posterior layer of the hepatoduodenal ligament runs over the caudate process of the liver
Posteriorly: inferior vena cava
Floor: upper border of the first part of the duodenum
The anterior and posterior walls of the foramen are normally
apposed, which partly explains why patients can develop large fluid
collections isolated to the greater or lesser sac

Rapid control of the hepatic artery and portal vein can be obtained by compression of the free edge of the lesser omentum (a ‘Pringle’ manoeuvre), which is a potentially useful technique in liver trauma and surgery.

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.

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

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

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

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

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