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.

Lorazepam is an intermediate-acting benzodiazepine that binds to the GABA-A receptor subunit to increase the frequency of chloride channel opening and cause membrane hyperpolarization.

Lorazepam has emerged as the preferred benzodiazepine for acute management of status epilepticus. Lorazepam differs from diazepam in two important respects. It is less lipid-soluble than diazepam, with a distribution half-life of two to three hours versus 15 minutes for diazepam. Therefore, it should have a longer duration of clinical effect. Lorazepam also binds the GABAergic receptor more tightly than diazepam, resulting in a longer duration of action. The anticonvulsant effects of lorazepam last six to 12 hours, and the typical dose ranges from 4 to 8 mg. This agent also has a broad spectrum of efficacy, terminating seizures in 75-80% of cases. Its adverse effects are identical to those of diazepam. Thus, lorazepam also is an effective choice for acute seizure management, with the added possibility of a longer duration of action than diazepam.

Phenobarbitone is a long-acting barbiturate that binds to GABA-A receptor site and increase the duration of chloride channel opening. It also blocks glutamic acid neurotransmission, and, at high doses, can block sodium channels. It is considered as the drug of choice for seizures in infants.

Phenytoin is an anti-seizure drug that blocks voltage-gated sodium channels. It is preferred in prolonged therapy of status epilepticus because it is less sedating.

In cases wherein airway protection is required, thiopentone and propofol are the preferred drugs.

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.

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.

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.

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.

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.

Ligamentum venosum is an anterior relation of the liver: The ligamentum venosum, the fibrous remnant of the ductus venosus of the fetal circulation, lies posterior to the liver. It lies in the fossa for ductus venosus that separates the caudate lobe and the left lobe of the liver.

The portal triad contains three important tubes: 1. Proper hepatic artery 2. Hepatic portal vein 3. Bile ductules It also contains lymphatic vessels and a branch of the vagus nerve.

The bare area of the liver is a large triangular area that is devoid of any peritoneal covering. The bare area is attached directly to the diaphragm by loose connective tissue. This nonperitoneal area is created by a wide separation between the coronary ligaments.

The porta hepatis is a fissure in the inferior surface of the liver. All the neurovascular structures (except the hepatic veins) and hepatic ducts enter or leave the liver via the porta hepatis. It contains the sympathetic branch to the liver and gallbladder and the parasympathetic, hepatic branch of the vagus nerve. The caudate lobe (segment I) lies in the lesser sac on the inferior surface of the liver between the IVC on the right, the ligamentum venosum on the left, and the porta hepatis in front.

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

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

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

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

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

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

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

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

An acetylcholinesterase inhibitor or anticholinesterase is a chemical that inhibits the cholinesterase enzyme from breaking down acetylcholine (ACh) therefore increasing the level and duration of action of the neurotransmitter acetylcholine(ACh).

ACh stimulates postganglionic receptors to produce the following effects:

Salivation
Lacrimation
Defecation
Micturition
Sweating
Miosis
Bradycardia, and
Bronchospasm.

Since these effects are produced by muscarine, they are referred to as muscarinic effects, and the postganglionic receptors are called muscarine receptors.

SLUD (Salivation, Lacrimation, Urination, Defecation – and emesis) is usually encountered only in cases of drug overdose or exposure to nerve gases. It is a syndrome of pathological effects indicating massive discharge of the parasympathetic nervous system.

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

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

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

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

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

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

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

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

When VAT is detected, patients with PVo2 of ©½10€…ml/kg/min have a high event rate.

Type I – immediate hypersensitivity reaction

Examples are: Atopy, urticaria, Anaphylaxis, Asthma( IgE mediated).

Type II – Antibody mediated cytotoxic reaction

Examples are: Autoimmune haemolytic anaemia, Thrombocytopenia( IgM or IgG mediated).

Type III – Immune complex mediated reaction

Examples are: Serum sickness,SLE – IgG., Farmers lungs, rheumatoid arthritis

Type IV – Delayed hypersensitivity reaction

Examples are: Contact dermatitis, drug allergies.

Type V – Autoimmune

Graves’
Myasthenia – IgM or IgG.

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)

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

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

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

Adrenaline acts on α1, α2, β1, and β2 receptors and also on dopamine receptors (D1, D2) and have sympathomimetic effects.

Natural catecholamines are Adrenaline, Noradrenaline, and Dopamine

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

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

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

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

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

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

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

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

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

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.

The renal arteries branch from the abdominal aorta just below the origin of the superior mesenteric artery. The right renal artery is higher and longer than the left renal artery. The left renal artery passes behind the left renal vein, the body of the pancreas, and the splenic vein.

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

T10 – oesophageal opening in the diaphragm

T12 – Coeliac trunk, aortic hiatus in the diaphragm

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta.

Muscle fibre myosin ATPase histochemistry is used to divide the biochemical classification into two groups: type 1 and type II.

Type I (slow twitch) muscle fibres rely on aerobic glycolytic and aerobic oxidative metabolism to function. They have a lot of mitochondria, a good blood supply, a lot of myoglobin, and they don’t get tired easily.

Because they contain more motor units, Type II (fast twitch) muscle fibres are thicker. They are more easily fatigued, but produce powerful bursts. The capillary networks and mitochondria are less dense in these white muscle fibres than in type I fibres. They have a low myoglobin content as well.

Muscle fibres of type II (fast twitch) are divided into three types:

Type IIa – aerobic/oxidative metabolism is used.
Type IIb – anaerobic/glycolytic metabolism is used by these fibres.

When compared to skeletal muscle, cardiac and smooth muscle twitch at a slower rate.

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

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 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.

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

A compound that contains an asymmetric centre (chiral atom or chiral centre) and thus can occur in two non-superimposable mirror-image forms (enantiomers) are called chiral compounds.

Desflurane, Halothane, and isoflurane are chiral compounds but Sevoflurane is not a chiral compound.

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

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

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

Small measurement units are denoted by the following SI mathematical prefixes:

1 deci = 0.1
1 milli = 0.001
1 micro = 0.000001
1 nano = 0.000000001
1 pico = 0.000000000001
1 femto = 0.000000000000001 (used to measure red blood cell volume)
1 atto = 0.000000000000000001.

The portal vein arises from the splenic and mesenteric veins, and is the biggest vessel in the portal venous system, accounting for about 75% of the hepatic blood flow.

It is responsible for draining blood from parts of the gastrointestinal system, the spleen, the pancreas and the gallbladder into the liver.

In an adult, the trachea is approximately 15 cm long. It extends at the level of the 6th cervical vertebra, from the lower border of the cricoid cartilage.

The trachea terminates between T4 and T6 at the carina or bronchial bifurcation. This variation is because of changes during respiration.

The trachea has 16-20 C-shaped cartilaginous rings that maintain its patency.

The trachea is first of the 23 generations of air passages in the tracheobronchial tree (not 25), from the trachea to the alveoli..

The inferior thyroid arteries which are branches of the thyrocervical trunk, arise from the first part of the subclavian artery and supplies the trachea.