Bilirubin is formed by metabolizing heme, mostly from haemoglobin in red blood cells.

Bilirubin is conjugated to glucuronic acid in the hepatocytes by the glucuronyl transferase enzyme in order to enable it to become soluble and allow for its secretion across the canalicular membrane and into bile.

The conjugation process is increased by rifampicin and decreased by valproate.

Gilbert’s syndrome is caused by a decrease in glucuronyl transferase in the hepatic system, decreasing the transport of bilirubin into the hepatocyte, causing unconjugated bilirubinaemia.

Crigler-Najjer syndrome is caused by mutations in the genes responsible for hepatic glucuronyl transferase, decreasing the activity of the enzyme, meaning bilirubin cannot be conjugated, causing unconjugated bilirubinaemia.

Dubin-Johnson syndrome does not cause an impairment in the conjugation of bilirubin, but it blocks the transport of bilirubin out of the hepatocyte resulting in conjugated bilirubinaemia.

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

Selection bias is when randomisation is not achieved.

Attention bias refers to the person’s failure to consider various alternatives when he pre occupied by some other thoughts.

Instrument bias is related to the experience and extent of familiarization of the participating individuals with the test.

Co intervention bias is characterized by the groups receiving different co interventions.

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 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

To begin, one must determine the child’s approximate weight. There are a variety of formulas to choose from. It is acceptable to use the advanced paediatric life support formula:

(Age + 4) 2 = Weight

A 5-year-old child will weigh around 18 kilogrammes.

10 mcg/kg (0.1 ml/kg of 1 in 10 000 adrenaline) = 180 mcg is the appropriate dose of intravenous or intraosseous adrenaline.

The correct energy level to deliver is 4 J/kg, which equals 72 joules.

The pad size that is appropriate for this patient is 8-12 cm. For an infant, a 4.5 cm pad is appropriate.

To allow adequate separation in infants and small children, the pads should be placed anteriorly and posteriorly on the chest.

When using a bag and mask to ventilate, take two breaths for every 15 chest compressions. If chest compressions are being applied intubated and without interruption, a ventilation rate of 10-20 breaths per minute should be given.

Chest compressions should be done at a rate of 100-120 per minute, the same as an adult.

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.

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 midgut gives rise to the appendix.
At week 6, the caecal diverticulum appears and is the precursor for the cecum and vermiform appendix. The cecum and appendix undergo rotation and descend into the right lower abdomen. The appendix can take up various positions:
1. Retrocecal appendix: behind the cecum
2. Retrocolic appendix: behind the ascending colon
3. Pelvic appendix: appendix descends into the pelvis

The appendix grows in length so that at birth, it is long and worm-shaped, or vermiform. After birth, the caecal wall grows unequally, and the appendix comes to lie on its medial side.

The midgut develops into the distal duodenum, jejunum, ileum, cecum, appendix, ascending colon, and proximal 2/3 of the transverse colon.

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.

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

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

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

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

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

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

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

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

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

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 posterior pituitary and the hypothalamus are connected by the pituitary stalk. It contains in the pituitary sella and has the optic chiasm and hypothalamus as superior relations.

The anterior pituitary produces thyroid-stimulating hormone (TSH), luteinising hormone (LH) and follicle-stimulating hormone (FSH) . These hormones are Glycoproteins and share a common alpha subunit with unique beta subunits.

The secretion of pituitary hormones are pulsatile. Examples are LH, adrenocorticotropic hormone (ACTH) and growth hormone (GH).

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

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

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

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

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

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

The anterior cardiac vein drains directly into the right atrium.

This patient has been shifted to a sulfonylurea drug whose most common side effect is hypoglycaemia. Similar symptoms can arise in a patient on insulin too. The signs and symptoms are consistent with a hypoglycaemic attack and include tachycardia, altered consciousness, and behaviour. This needs to be treated as an emergency with rapid correction of the blood glucose level using glucose or IV 20% dextrose.

In a hypoglycaemic attack, the body undergoes stress and releases hormones to increase blood glucose levels. These include:
Glucagon
Cortisol
Adrenaline

Adrenaline or epinephrine is the hormone responsible for this patient’s condition and is primarily produced in the medulla of the adrenal gland. It functions primarily to raise cardiac output and raise blood glucose levels in the blood.

Alpha-cells of the islets of Langerhans produce the hormone glucagon, which has opposing effects to insulin.

Follicular cells of the thyroid gland produce and secrete thyroid hormones. Thyroid hormones can cause similar symptoms, but it is unlikely with the patient’s medical history.

Post-ganglionic neurons of the sympathetic nervous system use norepinephrine as a neurotransmitter. Adrenaline can be made in these cells, but it is not their primary production site.

Zona fasciculata of the adrenal cortex is the main site for the production of cortisol.

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

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

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

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

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.

Level 1 – High-quality randomised controlled trial with statistically significant difference or no statistically significant difference but narrow confidence intervals (prospective controlled)

Level 2 – Prospective comparative study (prospective uncontrolled)

Level 3 – Case-control study, retrospective comparative study (retrospective controlled)

Level 4 – Case series (retrospective uncontrolled)

Level 5 – Expert opinion.

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)

An epidemic is declared when the increase in a give disease is above a certain level in a specific interval of time.

An endemic is the general, usual level of a disease in a population at a particular time.

A pandemic is an epidemic that is spread across many countries and continents.

The patient’s diagnosis is microcytic hypochromic anaemia which is often as a result of iron deficiency and thalassaemia.

Macrocytic anaemia is often caused by folate and B12 deficiencies and alcohol abuse.

Normocytic normochromic anaemia is often caused by acute blood loss, haemolytic anaemia, anaemia of chronic disease and leucoerythroblastic anaemias.

Normally, at rest vagal influence is dominant producing the heart rate of 60-80 beats per minute even if the intrinsic automaticity of Sinoatrial Node is 100-110 beats per minute.

The transplanted heart has no autonomic nervous supply. So, it will respond to endogenous and exogenous catecholamine. This loss of parasympathetic innervation is responsible for the tachycardia in this patient.

Hypokalaemia can cause myocardial excitability and potential for ventricular ectopic and supraventricular arrhythmias. Hypothyroidism is also unlikely to cause tachycardia in this patient.

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)

Oxygen delivery depends on 2 variables.
1) Content of oxygen in blood
2) Cardiac output

Oxygen content (arterial) = (Hb (g/dL) x 1.39 x SaO2 (%) ) + (0.023 x PaO2 (kPa))

Oxygen content (mixed venous) = (Hb (g/dL) x 1.39 x mixed venous saturation) + (0.023 x mixed venous partial pressure of oxygen in kPA)

Huffner’s constant = 1.39 = 1g of Hb binds to 1.39 ml of O2

Oxygen delivery DO2 (ml/min) = 10 x Cardiac output (L/min) x Oxygen content
Normally 1000ml/min

Oxygen consumption VO2 (ml/min) = 10 x Cardiac output (L/min) x Difference in arterial and mixed venous oxygen content
Normally 250 ml/min

Oxygen extraction ratio (OER) = VO2/DO2
Normally approximately 25%

Prednisolone 5 mg is the same as 20 mg hydrocortisone.

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

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

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

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

Superior vena cava is the main vein bringing blood back to the heart. It can get partially or completely blocked by various causes, the most common being due to malignant tumours of the mediastinum.

There are collateral pathways that form in long-standing cases with 60% or more stenosis and continue venous drainage in cases of superior vena obstruction. The collaterals are classified into four as follows:

1. The azygos-hemiazygos pathway
Azygos, hemiazygos, intercostal, and lumbar veins.

2. The internal and external mammary pathway
internal mammary, superior epigastric, and inferior epigastric veins and superficial veins of the thorax.

3. The lateral thoracic pathway
Lateral thoracic, thoracoepigastric, superficial circumflex, long saphenous, and femoral veins to collateralize to the IVC.

4. The vertebral pathway
Innominate, vertebral, intercostal, lumbar, and sacral veins to collateralize to the azygos and internal mammary pathways.

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.