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.

Based on the laboratory reports, the patient is suffering from significant hyponatremia. The symptoms of hyponatremia are mainly neurological and depend on the severity and rapidity of onset of hyponatremia.

Patient symptom according to the hyponatremia level is correlated below:

125 – 130mmol/L – Nausea and malaise
115 – 125mmol/L – Headache, lethargy, seizures, and coma
<120mmol/L - Up to 11% present with coma.

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.

The following units are derived SI units of measurement.

Energy or work: kg.m2.s-2
The Joule (J) is the energy transferred to an object when a force of one newton acts on that object in the direction of its motion through a distance of one meter or N.m.

Power: kg.m2.s-3
The Watt (W) = rate of transfer of energy or Joule per second J/s.

Force: kg.m.s-2
One Newton (N) which is the international unit of measure for force = 1 kilogram meter per second squared. 1 Newton of force is the force required to accelerate an object with a mass of 1 kilogram 1 meter per second per second.

Volt: kg.m2.s-3.A-1
The volt (V) is defined as the potential difference across a conductor when a current of one ampere dissipates one watt of power or W/A.

Pressure: kg.m-1.s-2
A pascal (Pa) is force per unit area or N/m2.

Body fluid compartments in a 70kg male:
Total volume=42L (60% body weight)
Intracellular fluid compartment (ICF) =28L
Extracellular fluid compartment (ECF) = 14L

ECF comprises:
Intravascular fluid (plasma) = 3L
Extravascular fluid = 11L

Extravascular fluids comprises:
Interstitial fluid = 10.5L
Transcellular fluid = 0.5L

Penicillinase is a narrow spectrum ?-lactamase that opens the ?-lactam ring and inactivates Penicillin G and some closely related congeners. The majority of Staphylococci and some strains of gonococci, B. subtilis, E. coli, and a few other bacteria produce penicillinase.

N. meningitidis is sensitive to penicillin and less than 20% resistance is found in pseudomonas.

The upper limb venous drainage is divided into superficial and deep. The superficial veins are accessible to draw blood for investigations. The cephalic, basilic, and median cubital veins are superficial veins.

The median cubital vein connects the cephalic vein and basilic vein. It is located anteriorly in the antecubital fossa and is preferred for venepuncture due to its palpability and ease of access.

The basilic vein and cephalic vein are the primary veins that drain the upper limb. They begin as the dorsal venous arch. The basilic vein originates from the ulnar side, while the cephalic vein originates from the radial side of the dorsal arch of the upper limb.

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.

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

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

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

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

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

A passive leg raise can lead to transient increases in blood pressure and stroke volume as it increased the amount of venous return to the heart. Venous return increases in this situation as it transfers a larger volume of blood from the lower limbs to the right heart. It therefore mimics a fluid challenge. However its effects are short lasting and often lead to minimal increases in blood pressure. It therefore should not be used to treat shock in isolation. The passive leg raise is useful in determining the likelihood that a patient with shock will respond to fluid resuscitation.

Stroke volume (via a cardiac monitor) and/or pulse pressure (via an arterial line) should be measured to assess the effects of a passive leg raise. An increase in stroke volume by 9% or in pulse pressure by 10% are considered indicative of fluid responsiveness.

Blood that enters the ventricles during diastole causes stretching of sarcomeres within cardiac muscle. The extent to which they stretch is proportional to the strength of ventricular muscle contraction. Therefore, the venous return (amount of blood returned to the heart) is proportional to stroke volume. The end diastolic volume is determined by venous return and is also proportional to stroke volume.

Cardiac muscle contraction strength is dependent on the action of adrenaline and noradrenaline, but these hormones contribute to cardiac contractility, not to stroke volume.

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

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.

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.

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.

Once the decision to deliver a baby by caesarean section has been made, it should be carried out with a level of urgency commensurate with the baby’s risk and the mother’s safety.

There are four types of caesarean section urgency:

Category 1: A threat to the life of the mother or the foetus. 30 minutes to make a delivery decision
Category 2 : Maternal or foetal compromise that is not immediately life threatening. In most cases, the decision to deliver is made within 75 minutes.
Category 3 – Early delivery is required, but there is no risk to the mother or the foetus.
Category 4: Elective delivery at a time that is convenient for both the mother and the maternity staff.

There may be evidence of foetal compromise in the example above (late foetal pulse decelerations and a borderline pH).

Blood samples from the foetus:
normal: 7.25 or above
borderline: 7.21 to 7.24
abnormal: 7.20 or below

When a foetal deceleration occurs, the mother should be given oxygen, kept in a left lateral position, and given a tocolytic if the foetal deceleration is hyper stimulating. Maintaining adequate hydration will reduce the likelihood of a caesarean section.

Phase 2 trials involve patients that are suffering from the disease under study and are associated with determining the efficiency and the optimum dosage of the drug.

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.

Phase 1 is associated with assessing whether a drug is safe to use or not. The process is extensive and can take up to several months. It also involves healthy participants (less than 100) that are paid to take part in the study. The side effects upon increasing dosage are also addressed by the study. The effects the drug has on humans including how its absorbed, metabolized and excreted are studied. Approximately 70% of the drugs pass this phase.

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 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.

BMR is lower in females than males.

It decreases with increasing age.

There is an increase in BMR with increased muscle (i.e. lean tissue)

BMR is increased in stress and illness. There is also an catabolic state in these conditions.

Metronidazole is a nitroimidazole antiprotozoal drug that is selectively absorbed by anaerobic bacteria and sensitive protozoa. Once taken up be anaerobes, it is nonenzymatically reduced by reacting with reduced ferredoxin. This reduction results in products that accumulate in and are toxic to anaerobic cells. The metabolites of metronidazole are taken up into bacterial DNA, forming unstable molecules. This action occurs only when metronidazole is partially reduced, and, because this reduction usually happens only in anaerobic cells, it has relatively little effect on human cells or aerobic bacteria.

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.

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.

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.

The following is the Advanced Trauma Life Support (ATLS) classification of haemorrhagic shock:

Class I haemorrhage:
It has blood loss up to 15%. There is very less tachycardia, and no changes in blood pressure, RR or pulse pressure. Usually, fluid replacement is not required.

Class II haemorrhage:
It has 15-30% blood loss, equivalent to 750 – 1500 ml. There is tachycardia, tachypnoea and a decrease in pulse pressure. Patient may be frightened, hostile and anxious. It can be stabilised by crystalloid and blood transfusion.

Class III haemorrhage:
There is 30-40% blood loss. It portrays inadequate perfusion, marked tachycardia, tachypnoea, altered mental state and fall in systolic pressure. It requires blood transfusion.

Class IV haemorrhage:
There is > 40% blood volume loss. It is a preterminal event, and the patient will die in minutes. It portrays tachycardia, significant depression in systolic pressure and pulse pressure, altered mental state, and cold clammy skin. There is need for rapid transfusion and surgical intervention.

Cough is an important defensive reflex that helps clear secretions and particulates from the airways. A complex reflex arc generates each cough.

The cough reflex begins with irritation of the cough receptors present in the epithelium of the trachea, main carina, branching points of large airways, and more distal smaller airways. These receptors are responsive to both mechanical and chemical stimuli.

Afferent pathway:
Impulses from stimulated receptors are transmitted via sensory nerve fibres of the vagus nerve (mainly) and glossopharyngeal nerve and travel to the medulla diffusely. CN 5 is also thought to contribute to the afferent limb. However, the vagus is the main nerve.

Central pathway:
The cough centre is located in the upper brain stem and pons

Efferent pathway:
Impulses from the centre travel via the vagus, phrenic nerve, and spinal motor nerves to the diaphragm, abdominal wall, and muscles.

The internal laryngeal nerve provides sensory innervation to the laryngeal mucosa, and injury to it will cause loss of sensation.

The internal laryngeal nerve lies inferior to the piriform recess mucous membrane, placing it at high risk of irritation or damage by objects which become lodged in the recess.

The internal laryngeal artery branches off the superior laryngeal artery accompanied by the superior laryngeal nerve, inferior to the thyroid artery which branches off the superior thyroid artery close to its bifurcation from the external carotid artery.

The derived SI unit of force is Newton.
F = m·a (where a is acceleration)
F = 1 kg·m/s2

The joule (J) is a converted unit of energy, work, or heat. When a force of one newton (N) is applied over a distance of one metre (Nm), the following amount of energy is expended:

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

The unit of velocity is metres per second (m/s or ms-1).

The watt (W), or number of joules expended per second, is the SI unit of power:

J/s = kg·m2·s-2/s
J/s = kg·m2·s-3

Pressure is measured in pascal (Pa) and is defined as force (N) per unit area (m2):
Pa = kg·m·s-2/m2
Pa = kg·m-1·s-2

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

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

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

The 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

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 intercostal nerve block is used for therapeutic and diagnostic purposes. Intercostal nerve blocks manage acute and chronic pain in the chest area. Common indications are chest wall surgery and shingles or postherpetic neuralgia.

An intercostal nerve block is also an effective option for the management of pain associated with chest trauma and rib fractures. These blocks have been shown to improve oxygenation and respiratory mechanics, and offer pain relief that is comparable to that of epidural analgesia.

This technique, however, is limited by the relatively large doses of local anaesthetic required, and relatively high intravascular uptake from the intercostal space, increasing risk of local anaesthetic toxicity.

Campylobacter is the commonest bacterial cause of infectious intestinal disease in the UK. The majority of cases are caused by the Gram-negative bacillus Campylobacter jejuni which is spread by the faecal-oral route. The incubation period is 1-6 days.

Features include a prodrome phase with headaches and malaise, then diarrhoea occurs which is often bloody.
There is often abdominal pain which may mimic appendicitis.

It is usually self-limiting but treatment is warranted if the infection is severe or the infection occurs in an immunocompromised patient.
Severe infection comprises of high fever, bloody diarrhoea, or more than eight stools per day or symptoms last for more than one week.
This management would include antibiotics and the first-line antibiotic is clarithromycin.
Ciprofloxacin is an alternative but there are strains with decreased sensitivity to ciprofloxacin which can be frequently isolated.

Complications include:
1.Guillain-Barre syndrome may follow Campylobacter
2. Jejuniinfections
3. Reactive arthritis
4. Septicaemia, endocarditis, arthritis

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 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

A damped sine wave is a smooth, periodic oscillation with an amplitude that approaches zero as time goes to infinity. In other words, the wave gets flatter as the x-values become larger.

Critical damping is defined as the threshold between overdamping and underdamping. In the case of critical damping, the oscillator returns to the equilibrium position as quickly as possible, without oscillating, and passes it once at most.

In overdamping, the system moves slowly towards the equilibrium. An underdamped system moves quickly to equilibrium, but will oscillate about the equilibrium point as it does so.

Optimal damping has a damping coefficient of around 0.64-0.7. It maximizes frequency response, minimizes overshoot of oscillations, and minimizes phase and amplitude distortion.

In an undamped system, the amplitude of the waves that are being generated remain unchanged and constant over time.

Maintenance therapy aims to replace water and electrolytes lost under ordinary conditions. In the perioperative period, maintenance fluid administration may not sufficiently account for the increased fluid requirements caused by third-space losses into the interstitium and gut. Specific recommendations vary with the patient, the procedure, and the type and amount of fluid administered during the operation. The fluid for maintenance therapy replaces deficits arising primarily from insensible losses and urinary or gastrointestinal (GI) losses.

The maintenance fluid volume can be computed using the Holliday-Segar method.

Body weight Fluid volume
first 10 kg 4 ml/kg/hr
next 10-20 kg 2 ml/kg/hr
>20 kg 1 ml/kg/hr

In the past few years, there has been growing recognition of the increased risk of hyponatremia in hospitalized children in intensive care and postoperative settings who receive hypotonic maintenance fluids. Several studies, including a randomized controlled trial and a Cochrane analysis, found that the use of isotonic fluids is associated with fewer electrolyte derangements and concluded that isotonic maintenance fluids are preferable to hypotonic solutions in hospitalized children.

A European consensus statement suggests that an intraoperative fluid should have an osmolarity close to the physiologic range in children in order to avoid hyponatremia, an addition of 1-2.5% in order to avoid hypoglycaemia, lipolysis or hyperglycaemia and should also include metabolic anions as bicarbonate precursors to prevent hyperchloremic acidosis.

A rate of 40 ml/hr is suboptimal.

If 0.9% NaCl with 0% glucose is given at a rate of 65 ml/hr, despite of the correct infusion rate, large volumes can lead to hyperchloremic acidosis.

If 0.18% NaCl with 4% glucose is given at a rate of 65 ml/hr, infusion of this fluid regimen can lead to hyponatremia because of its hypotonicity.

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

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

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

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

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

The posterior inferior cerebellar artery is the largest branch arising from the distal portion of the vertebral artery which forms the basilar artery. It is one of the arteries responsible for providing blood supply to the brain’s cerebellum.

The labyrinthine artery (auditory artery) is a long and slender artery which arises from the basilar artery and runs alongside the facial and vestibulocochlear nerves into the internal auditory meatus.

The posterior cerebellar artery is one of two cerebral arteries supplying the occipital lobe with oxygenated blood. It is usually bigger than the superior cerebellar artery. It is separated from the vessel near its origin by the oculomotor nerve.

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

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.

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)

Laminar flow can be defined as the motion of a fluid where every particle in the fluid follows the same path of its previous particles. The following are properties of laminar flow of gas or fluids:

1. Smooth unobstructed flow of gas through a tube of relatively uniform diameter
2. Few directional changes
3. Slow, steady flow through straight smooth, rigid, large calibre, cylindrical tube
4. Outer layer flow slower than the centre due to friction, results in discrete cylindrical layers, or streamlines
5. Double flow by doubling pressure as long as the flow pattern remains laminar

Poiseuille’s Law relates the factors that determine laminar flow. It indicates the degree of resistance to fluid flow through a tube. The resistance to fluid flow through a tube is directly related to the length, flow and viscosity; and inversely related to the radius of the tube to the fourth power. This means that, when the radius is doubled, there is increase in flow by a factor of 16.

The number of osmoles (Osm) of solute per litre (L) of solution (Osmol/L) is the unit of measurement for solute concentration. The calculated serum osmolality assumes that the primary solutes in the serum are sodium salts (chloride and bicarbonate), glucose, and urea nitrogen.

2 (Na + K) + Glucose + Urea (all in mmol/L) = calculated osmolarity

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

Sodium and potassium ions clearly contribute the most to plasma osmolarity. Glucose and urea, on the other hand, are less so.

The osmolarity of normal serum is 285-295 mOsm/L. Temperature and pressure affect osmolality, and this calculated variable is less than osmolality for a given solution.

The number of osmoles (Osm) of solute per kilogramme (Osm/kg) is a measure of osmolality, which is also a measure of solute concentration. Temperature and pressure have no effect on the value. An osmometer is used to measure it in the lab. Osmometers rely on a solution’s colligative properties, such as a decrease in freezing point or a rise in vapour pressure.

The osmolar gap (OG) is calculated as follows:

OG = osmolaRity calculated from measured serum osmolaLity

Excess alcohols, lipids, and proteins in the blood can all contribute to the difference.

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 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

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

The following are symptoms of moderate asthma:

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

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

Airway obstruction increases the functional residual capacity.

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

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

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

The reasons for adding adrenaline to a local anaesthetic solution are:

1. To Increase the duration of block
2. To reduce absorption of the local anaesthetic into the circulation
3. To Increase the upper safe limit of local anaesthetic (2.5 mg/kg instead of 2 mg/kg, in this case).

The addition of adrenaline to bupivacaine does not affect its potency, lipid solubility, protein binding, or pKa(8.1 with or without adrenaline).

The pH of bupivacaine is between 5-7. Premixed with adrenaline, it is 3.3-5.5.
The onset of a local anaesthetic and its ability to penetrate membranes depends upon degree of ionisation. Compared with the ionised fraction, unionised local anaesthetic readily penetrates tissue membranes to site of action. The onset of action of solution B is slower. this is because the relationship between pKa(8.1) and pH(3.3-5.5) of the solution results in a greater proportion of ionised local anaesthetic molecules compared with solution A.

The answer is anterior to the spermatic cord.

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

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

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.

The most common cause of hypoparathyroidism is injury or removing the parathyroid glands. They can be injured accidentally during surgery to remove the thyroid as they are located posterior to the thyroid gland.

A result of both low parathyroid hormone and low calcium is likely to mean that the parathyroid glands are not responding to hypocalcaemia. The hypocalcaemia can cause confusion, and the stay in the hospital is likely to refer to her surgery.

While a parathyroid adenoma is fairly common and can cause hypoparathyroidism, it much more likely causes hyperparathyroidism.

Chronic kidney disease is likely to cause hypocalcaemia, which would increase parathyroid hormone production in an attempt to increase calcium levels, causing hyperparathyroidism. Vitamin D is activated by the kidneys and then binds to calcium to be absorbed in the terminal ileum so that a deficiency would cause hyperparathyroidism.

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.

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.

Carbonic anhydrase is an enzyme which contains zinc and can be found in:
1. Erythrocytes
2. Pulmonary endothelium
3. The intestine
4. Pancreas
5. Cardiac muscle and skeletal muscle.

To date, there have been seven isoenzymes identified. Of note, isoenzyme IV is found in the brush border of the proximal convoluted tubule and isoenzyme II is found within the luminal cells.

Acetazolamides a carbonic anhydrase inhibitor and is used as prophylaxis against mountain sickness and in glaucoma management.

Spironolactone is a potassium diuretic and is an aldosterone antagonist.

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.

Case control studies in particular are prone to recall bias, people who are suffering from COPD might sometimes relate the ailment to marijuana usage in past and hence contrary to the control group, they are more able to describe to what extent they have been using the drug in the past.

As recommended, all the doctors should make sure that there practice is based on evidence and thus it is paramount that the doctors learn to appraise the paper in a critical manner i.e. ability to detect any potential source of bias.

Detection Bias: Outcomes are more looked for in one group than the other.

Observer Bias: Subjectivity of observers regarding the outcome.

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

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

Response Bias: The participants that filled out the response forms containing information that was going to be used for a trial, don’t represent the target population.

The ideal gas equation makes the following assumptions:

The gas particles have a small volume in comparison to the volume occupied by the gas.
Between the gas particles, there are no forces of interaction.
Individual gas particle collisions, as well as gas particle collisions with container walls, are elastic, meaning momentum is conserved.
PV = nRT
Where:

P = pressure
V = volume
n = moles of gas
T = temperature
R = universal gas constant

Helium is a monoatomic gas with a small helium atom. The attractive forces between helium atoms are small because the helium atom is spherical and has no dipole moment. Because helium atoms are spherical, collisions between them approach the ideal state of elasticity.

Most real gases behave qualitatively like ideal gases at standard temperatures and pressures. When intermolecular forces and molecular size become important, the ideal gas model tends to fail at lower temperatures or higher pressures. It also fails to work with the majority of heavy gases.

Helium, argon, neon, and xenon are noble or inert gases that behave the most like an ideal gas. Xenon is a noble gas with a much larger atomic size than helium.

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.

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.

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.

The usual method of calculating the dose of a drug to be given to patients of normal weight is to use total body weight (TBW). This is because the lean body weight (LBW) and ideal body weight (IBW) dosing scalars are similar in these patients.

Because the LBW and fat mass do not increase in proportion in patients with morbid obesity, this is not the case. Drugs that are lipid soluble, such as propofol or thiopentone, can cause a relative overdose. Lean body mass is a better scalar in these situations.

Suxamethonium has a small volume of distribution, so the dose is best calculated using the TBW to ensure optimal and deep intubating conditions. The higher dose was justified because these patients’ plasma cholinesterase activity was elevated.

Other scalars include:

The dose of highly lipid soluble drugs like benzodiazepines, thiopentone, and propofol can be calculated using lean body weight (LBW). The formula LBW = IBW + 20% can be used on occasion.

Fentanyl, rocuronium, atracurium, vecuronium, morphine, paracetamol, bupivacaine, and lidocaine are all administered with LBW.

Formulas can be used to calculate the ideal body weight (IBW). There are a number of drawbacks, including the fact that patients of the same height receive the same dose, and the formulae do not account for changes in body composition associated with obesity. Because IBW is typically lower than LBW, administering a drug based on IBW may result in underdosing. The body mass index (BMI) isn’t used to calculate drug dosage directly.

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

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

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

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

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

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

The 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

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.

Because the patient has mild systemic disease, he is ASA 2 and the procedure will be performed under local anaesthesia.

The following factors should be considered when requesting preoperative investigations:

Indications derived from a preliminary clinical examination
Whether or not a general anaesthetic will be used, the possibility of asymptomatic abnormalities, and the scope of the surgery.

No special investigations are needed if the patient has no history of significant systemic disease and no abnormal findings on examination during the nurse-led assessment.

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

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

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

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

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

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.

The half life of Retinol binding protein (RBP) is 10-12 hours and therefore reflects more acute changes in protein metabolism than any of these proteins. Therefore it is not commonly used as a parameter for nutritional assessment.

The half life of Transthyretin (thyroxine binding pre-albumin) is only one to two days and so levels are less sensitive and this protein is not an albumin precursor. 15 mg/dL represents early malnutrition and a need for nutritional support.

Albumin levels have been frequently as a marker of nutrition but this is not a very sensitive marker. It’s half life more than 30 days and significant change takes some time to be noticed. Also, synthesis of albumin is decreased with the onset of the stress response after burns. Unrelated to nutritional status, the synthesis of acute phase proteins increases and that of albumin decreases.

A more accurate indicator of protein stores is transferrin. It’s response to acute changes in protein status is much faster. The half life of serum transferrin is shorter (8-10 days) and there are smaller body stores than albumin. A low serum transferrin level is below 200 mg/dL and below 100 mg/dL is considered severe. Serum transferrin levels can also affect serum transferrin level.

Fibronectin is used a nutritional marker but levels decrease after seven days of starvation. It is a glycoprotein which plays a role in enhancing the phagocytosis of foreign particles.

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)

Every surgical procedure is associated with a stress response which comprises a number of endocrine, metabolic, and immunological changes triggered by neuronal activation of the hypothalamic-pituitary-adrenal axis. The overall metabolic effect of the stress response to surgery includes an increase in secretion of catabolic hormones, such as cortisol and catecholamine, and a decrease in secretion of anabolic hormones, such as insulin and testosterone. The increase in levels of catabolic hormones in plasma stimulates glucose production, and there is a relative lack of insulin together with impaired tissue insulin sensitivity and glucose utilization, which is called insulin resistance. Consequently, blood glucose concentrations will increase, even in the absence of pre-existing diabetes.

A study compared the effects of spinal and general anaesthesia on changes in blood glucose concentrations during surgery in nondiabetic patients. Although mean blood glucose concentrations showed a significant proportional increase during surgery in both groups, this effect was much more significant with general anaesthesia than with spinal anaesthesia. These results indicate that spinal anaesthesia is more effective than general anaesthesia in attenuating the hyperglycaemic response to surgery.

Wavelength can be computed as follows:

Wavelength = velocity/frequency

In the given problem, the values stated are:

Frequency = 10 x 10^6
Velocity = 1540 meters per second

Wavelength = 1540/(10×10^6)
Wavelength = 1540/10,000,000 meters
Wavelength = 0.15 millimetres

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

It can be found as:

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

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

So,

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

ARR= (0.157-0.126)

ARR= 0.031

NNT= 1/0.031

NNT=32.3

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

Drug A is a pure agonist for the receptor, with high intrinsic efficacy and affinity, according to the log-dose response curve.

Drug B, on the other hand, works as a competitive antagonist. It binds to the receptor but has no inherent efficacy. Drug A’s efficacy will not change, but its potency will be reduced.

A partial agonist is a drug with partial intrinsic efficacy and affinity for the receptor. Giving a partial agonist after a pure agonist will not increase receptor occupancy or decrease receptor activity, and thus will not affect drug A’s efficacy. The inverse agonist flumazenil can reverse all benzodiazepines.

An inverse agonist is a drug that binds to the receptor but has the opposite pharmacological effect.

A non-competitive antagonist is a drug that has affinity for a receptor but has different pharmacological effects and reduces the efficacy of an agonist for that receptor.

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.

Noradrenaline also called norepinephrine belongs to the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter.

They have sympathomimetic effects acting via adrenoceptors (?1, ?2,?1, ?2, ?3) or dopamine receptors (D1, D2).

May cause reflex bradycardia, reduce cardiac output and increase myocardial oxygen consumption

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

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

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

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

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

It can be found as:

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

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

So,

ARR= (0.04-0.03)

ARR= 0.01

NNT= 1/0.01

NNT=100

Sevoflurane is highly fluorinated methyl isopropyl ether widely used as an inhalational anaesthetic. It is suggested that sevoflurane preconditioning occurs via the opening of mitochondrial Potassium ATP dependent channel similar to that of Ischemic Preconditioning protection.

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

Thiopental has the longest elimination half-life of 6-15 hours.

Elimination half-life of other drugs are given as:
– Propofol: 5-12 h
– Methohexitone: 3-5 h
– Ketamine: 2 h
– Etomidate: 1-4 h

Control of Substances Hazardous to Health (COSHH) was established by government under the Health and Safety at Work act in 1989. Their employers work on identification and management of those substances that are dangerous to health. The implications for anaesthetists include gas scavenging, equipment contamination and environmental safety. Adequate ventilation is required in areas where anaesthetic gases are present. The minimum air supply that is legally required in each specific area is: Operating theatres: 0.65 m3/second. Anaesthetic rooms: 0.15 m3/s. Preparation rooms: 0.1 m3/s. Recovery rooms need 15 air changes per hour

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

In the neonatal stage, the tongue is usually large and comes to the normal size at the age of 1 year. The vocal cords lie inverse C4 and as it reaches the grown-up position inverse C5/6 by the age of 4 (not 1 year).

Due to the immature cricoid cartilage, the larynx lies more anterior in newborn children. That’s why the cricoid ring is the narrowest part of the paediatric respiratory tract, while in the adults the tightest portion of the respiratory route is vocal cords. The epiglottis is generally expansive and slants at a point of 45 degrees to the laryngeal opening.

The carina is the ridge of the cartilage in the trachea at the level of T2 in newborn (T4 in adults), that separates the openings of right and left main bronchi.

Neonates have a comparatively low number of alveoli and then this number gradually increases to a most extreme by the age of 8 (not 3 years).

Neonates are obligatory nose breathers and any hindrance can cause respiratory issues (e.g., choanal atresia).

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.

When drugs are bound to proteins, drugs cannot cross membranes and exert their effect. Only the free (unbound) drug can be absorbed, distributed, metabolized, excreted and exert pharmacologic effect. Thus, when amide local anaesthetics are bound to ?1-glycoproteins, their duration of action are reduced.

The potency of local anaesthetics are affected by lipid solubility. Solubility influences the concentration of the drug in the extracellular fluid surrounding blood vessels. The brain, which is high in lipid content, will dissolve high concentration of lipid soluble drugs. When drugs are non-ionized and non-polarized, they are more lipid-soluble and undergo more extensive distribution. Hence allowing these drugs to penetrate the membrane of the target cells and exert their effect.

Tissue pKa and pH will determine the degree of ionization.

The elimination of phenytoin follows first order kinetics. Plasma concentrations determine the rate of elimination. The relationship between drug X plasma concentration and time is described by an exponential process in the following equation used to describe the rate of elimination:

C = C0. e-kt

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

As enzyme systems become saturated when phenytoin concentrations are above the usual range, clearance of the medication becomes zero-order. The medication is metabolised at a constant pace, regardless of its plasma levels. Aspirin and ethyl alcohol are two more significant examples of medications that operate in this way.

A plot of drug concentration with time is a washout exponential curve.

A graph of concentration with time is a straight line i.e. Zero-order kinetics

The amount eliminated per unit time is constant defines the point at which zero order kinetics commences.

Elimination involves a rate-limiting reaction operating at its maximal velocity is incorrect.

The half life of the drug is proportional to the drug concentration in the plasma corresponds to a definition of first-order kinetics.

During glycolysis, 2,3-diphosphoglycerate (2,3-DPG) is
created in erythrocytes by the Rapoport-Luebering shunt.

The production of 2,3-DPG increases for several conditions
in the presence of decreased peripheral tissue O2 availability.
Some of these conditions include hypoxaemia, chronic lung
disease anaemia, and congestive heart failure. Thus,
2,3-DPG production is likely an important adaptive mechanism.

High levels of 2,3-DPG cause a shift of the curve to the right.
Low levels of 2,3-DPG cause a shift of the curve to the left,
as seen in states such as septic shock and hypophosphatemia.

When the eye is compressed or the extra-ocular muscles are tractioned, the oculocardiac reflex causes a decrease in heart rate.

The ophthalmic division of the trigeminal nerve provides the afferent limb. This synapses with the vagus nerve’s visceral motor nucleus in the brainstem. The efferent signal is carried by the vagus nerve to the heart, where increased parasympathetic tone reduces sinoatrial node output and slows heart rate.

The most common symptom is sinus bradycardia, but junctional rhythm and asystole can also occur.

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

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

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

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

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

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 Delphi is a group facilitation technique that seeks to obtain consensus on the opinions of `experts’ through a series of structured questionnaires (commonly referred to as rounds). By using successive questionnaires, opinions are considered in a non-adversarial manner, with the current status of the groups’ collective opinion being repeatedly fed back. Studies employing the Delphi make use of individuals who have knowledge of the topic being investigated

The correct answer is the clotting cascade, which occurs via a positive feedback mechanism. As clotting factors are attracted to a site, their presence attracts further clotting factors. This continues until a functioning clot is formed.

This patient has presented with symptoms of hypothyroidism and symptoms include weight gain, lethargy, cold intolerance, dry skin, coarse hair and constipation. It can be treated by replacing the missing thyroid hormone with levothyroxine which is a synthetic version of thyroxine (T4).

Serum carbon dioxide (CO2) is controlled via a negative feedback mechanism as well. Chemoreceptors can detect when the serum CO2 is high, and send an impulse to the respiratory centre of the brain to increase the respiratory rate. As a result, more CO2 is exhaled which lowers the serum concentration.

Cortisol is also released according to a negative feedback mechanism. Cortisol acts on both the hypothalamus and the anterior pituitary. Its action serve to decrease the formation of corticotrophin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), respectively. CRH acts on the anterior pituitary to release ACTH. This then acts on the adrenal gland to cause the release of cortisol. Thus, inhibition of CRH and ACTH formation results in high levels of cortisol which inhibit its further release.

Blood pressure (BP) is controlled via a negative feedback mechanism. Low BP results in renin-angiotensin-aldosterone system (RAAS) activation. This leads to vasoconstriction and retention of salt and water which increased BP.
Blood sugar is controlled via a negative feedback mechanism. A rise in blood sugar causes insulin to be released. Insulin acts to transport glucose into the cell which lowers blood sugar.

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

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

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

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

T cells possess specific glycoproteins and receptors on their surface.

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

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

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

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

The ideal agent for this case should have low blood: gas coefficient, pleasant smell, and high oil: gas coefficient (potent with a low Minimum alveolar coefficient (MAC)). Among the given options, Sevoflurane is perfect with 0.692 blood: gas partition coefficient and is low pungency, and is sweet.

Other drugs with their blood: gas partition coefficient and their smell are given as:
Blood/gas partition coefficient MAC Smell
Enflurane 1.8 1.68 Pungent, ethereal
Desflurane 0.42 7 Pungent, ethereal
Halothane 2.54 0.71 Sweet
Isoflurane 1.4 1.15 Pungent, ethereal

A higher frequency ultrasound comes with a better resolution of the digital image. Ultrasound with a frequency of 15 MHz is best used in imaging of superficial organs such as the thyroid gland, muscles, tendons and breasts whereas deep organs are better imaged using a lower frequency of 2-7MHz because of its ability for deeper penetration but lower resolution. These low frequency probes are also used to diagnose ascites, pleural effusions or can be used in echocardiography.

The US probe emits and then absorbs a reflected wave. Similar to brightness control, increasing the gain will amplify the return signal which is then attenuated by the tissue. This increases the signal to noise ratio.
A high frame rate, which basically means the number of times an image is updated onto the screen per second, improves the resolution of a moving 3D image which has become more accurate as the computing power has increased.

Widening of the image field can be obtained by altering the penetration depth which is obtained by changing the frequency of the US beam

The liver receives blood supply from two sources.
1. Hepatic artery proper
It arises from the celiac trunk via the common hepatic artery and brings oxygenated blood to the liver.
It contributes to approximately 30% of the blood supply of the liver.
2. Hepatic portal vein – supplies the liver with partially deoxygenated blood, carrying nutrients absorbed from the small intestine. It gets tributaries from the inferior mesenteric vein, splenic vein, and superior mesenteric vein

The inferior mesenteric artery supplies the hindgut.
The superior mesenteric artery supplies the pancreas and intestine up to the proximal two-thirds of the transverse colon.
The inferior phrenic artery supplies the inferior surface of the diaphragm and oesophagus.

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.

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.

Adequate humidification is vital to maintain homeostasis of the airway. Heat and moisture exchangers conserve some of the exhaled water, heat and return them to inspired gases. Many heat and moisture exchangers also perform bacterial/viral filtration and prevent inhalation of small particles. Heat and moisture exchangers are also called condenser humidifier, artificial nose, etc. Most of them are disposable devices with exchanging medium enclosed in a plastic housing. For adult and paediatric age group different dead space types are available. Heat and moisture exchangers are helpful during anaesthesia and ventilatory breathing system. To reduce the damage of the upper respiratory tract through cooling and dehydration inspiratory air can be heated and humidified, thus preventing the serious complications. Moreover, they are the most appropriate humidification devices used for routine anaesthesia.

Gases can be bubbled through water to increase humidity. Passing gas through water at room temperature causes the gas to cool due to latent heat of vaporisation. The water bath can be heated. This improves the efficiency of the device and also reduces the incidence of bacterial colonisation.

Nebulisers use a venturi system which employs the Bernoulli effect. A gas at high flow passes through a constriction causing the gas to accelerate, reducing its potential energy allowing other gases or liquids to be entrained. This can include medications or in the case of humidification, water vapour. The size of the water droplet produced by nebulisation determines where in the airway it is deposited. Standard nebulisers produced droplets of 4 microns in diameter and these are deposited in the upper airway and trachea. Efficacy can be improved by passing the droplets over an anvil which further reduces particle size. The most efficient form of nebuliser is the ultrasonic nebuliser. Here a transducer immersed in water and vibrated at a frequency of 3MHz produces1-2micron droplets. These particles easily reach the bronchioles and provide excellent humidification.

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.

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.

Randomized controlled trails will be analysed by the intention-to-treat (ITT) approach. It provides unbiased comparisons among the treatment groups. ITT analyses are done to avoid the effects of dropout, which may break the random assignment to the treatment groups in a study.

ITT analysis is a comparison of the treatment groups that includes all patients as originally allocated after randomization.

In order to include such participants in an analysis, outcome data could be imputed which involves making assumptions about the outcomes in the lost participants.

The arch of aorta gives rise to three main branches:
1. Brachiocephalic artery
2. Left common carotid artery
3. Left subclavian artery

The brachiocephalic artery then gives rise to the right subclavian artery and the right common carotid artery.

The right common carotid artery arises from the brachiocephalic trunk posterior to the sternoclavicular joint.

The coeliac trunk is a branch of the abdominal aorta.
The ascending aorta supplies the coronary arteries.

The potency of local anaesthetics is directly proportional to lipid solubility because they need to penetrate the lipid-soluble membrane to enter the cell.

Protein binding has a direct relationship with the duration of action because the higher the ability of the drug to bind with membrane protein, the higher is the duration of action.

Higher the pKa of a drug, slower the onset of action. Because a drug with higher pKa will be more ionized than the one with lower pKa at a given pH. Local anaesthetics are weak bases, and unionized form diffuses more rapidly across the nerve membrane than the protonated form. As a result drugs with higher pKa will be more ionized will diffuse less across the nerve membrane.

Because alpha glucosidase inhibitors slow starch digestion in the small intestine, glucose from a meal enters the bloodstream more slowly and can be matched more effectively by an impaired insulin response or sensitivity, glucose from a meal enters the bloodstream more slowly and can be matched more effectively by an impaired insulin response or sensitivity.

Biguanides decrease hepatic glucose output while increasing glucose uptake in peripheral cells.

The meglitinides are secretagogues that act on a different site of the KATP receptors.

Insulin secretion is stimulated by sulphonylureas, which stimulate insulin secretion from pancreatic beta cells. The KATP channels are inhibited by these substances.

Insulin-sensitive genes are influenced by thiazolidinediones, which increase the production of mRNAs for insulin-dependent enzymes. As a result, the cells make better use of glucose.

Always call for help early. This patient is at risk of gastro-oesophageal reflux, which is why a rapid sequence induction has been chosen. The patient is not pregnant, and the surgery is not urgent.

Plan A is to perform a rapid sequence induction under optimal conditions and secure the airway with a tracheal tube.

No more than three attempts with a direct laryngoscope (plus one attempt with a videolaryngoscope) should be made to intubate the trachea. Keep in mind that suxamethonium is wearing off. Ensuring adequate neuromuscular blockade at this stage is crucial; this might include administering a non-depolarizing relaxant if oxygenation can be maintained with bag-mask ventilation. Given the non-immediate nature of the surgery, there should be a low threshold to abandon intubation attempts and resort to Plan B.

An alternative strategy can then be planned.

The most important initial step is to declare a “failed intubation.” This will prevent further intubation attempts and alert your assistant that Plan A has failed. Maintaining oxygenation and anesthesia is also critical before implementing Plan B.

Do not administer another dose of suxamethonium. Insert a supraglottic airway if oxygenation fails and adequate ventilation cannot be maintained.

Plan D follows the declaration of a CICO (Cannot Intubate, Cannot Oxygenate) situation.

There are two types of defibrillators
AC defibrillator
DC defibrillator

AC defibrillator,
consists of a step-up transformer with primary and secondary winding and two switches. Since secondary coil consists of more turns of wire than the primary coil, it induces larger voltage. A voltage value ranging between 250V to 750V is applied for AC external defibrillator. And used to enable the charging of a capacitor.

DC defibrillator,
consists of auto transformer T1 that acts as primary of the high voltage transformer T2. Is an iron core that transfers energy between 2 circuits by electromagnetic induction. Transformers are used to isolate circuits, change impedance and alter voltage output. transformers do not convert AC to DC.

Diode rectifier composed of 4 diodes made of semiconductor material allows current to flow only in one direction. Alternating current (AC) passing through these diodes produces direct current (DC). Capacitor stores the charge in the form of an electrostatic field.

Capacitor is used to convert the rectified AC voltage to produce DC voltage but capacitors do not directly convert AC to DC.

Inductor induces a counter electromotive force(emf) that reduces the capacitor discharge value.

In step-down transformer primary coils has more turns of wire than secondary coil, so induced voltage is smaller in the secondary coil.

When the association among any two classes of object is defined by the presence of a third entity it is termed as indirect association. For an instance, the age of the employee may affect the rate of pay, which would have implications on job satisfaction. So, in this example, an indirect relationship between age and job satisfaction exists due to a third party i.e. rate of pay.

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.

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 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.

The neuroleptic malignant syndrome is a rare complication in response to neuroleptic or antipsychotic medication.

The main features are:
– Elevated creatinine kinase
– Hyperthermia and tachycardia
– Altered mental state
– Increased white cell count
– Insidious onset over 1-3 days
– Extrapyramidal dysfunction (muscle rigidity, tremor, dystonia)
– Autonomic dysfunction (Labile blood pressure, sweating, salivation, urinary incontinence)

Management is supportive ICU care, anticholinergic drugs, increasing dopaminergic activity with Amantadine, L-dopa, and dantrolene, and non- depolarising neuromuscular blockade drugs

Creatinine clearance is a test used to approximate the glomerular filtration rate (GFR) as an assessment of kidney function.

Creatinine is formed during the breakdown of dietary sources of meat and skeletal muscle. It is secreted at a consistent concentration and pace into the body’s circulation, and is easily filtered across the glomerulus without being reabsorbed or metabolized by the kidney.

It is represented mathematically as:
Creatinine clearance (CL) = U x V/P
where,
U: Urinary creatinine concentration (mg/mL)
V: Volume of urine (mL/min)
P: Plasma creatinine concentration (mg/mL)

Therefore, in this case:
CL: 1.25 x 1 = 125mL/min
0.1

Prerenal failure has a serum urea: creatinine ratio of >100, while acute kidney injury has a ratio of 40.
In prerenal failure, ADH levels are typically high, resulting in water, urea, and sodium resorption. The fractional sodium excretion is less than 1%, but it is greater than 2% in acute tubular necrosis.
Prerenal azotaemia has higher serum urea nitrogen/serum creatinine ratios (>20), whereas acute tubular necrosis has lower ratios (10-15). The normal range is between 12 and 20.
Urinary sodium is less than 20 in prerenal failure and greater than 40 in acute tubular necrosis.
Prerenal failure has a urine osmolality of >500, while acute tubular necrosis has an osmolality of 350.
Prerenal failure has a urine/serum creatinine ratio of >40, while acute tubular necrosis has a urine/serum creatinine ratio of 20.

The concentrations of serum urea or creatinine change in inverse proportion to glomerular filtration. Changes in serum creatinine concentrations are more reliable than changes in serum urea concentrations in predicting GFR. Creatinine is produced at a constant rate from creatine, and blood concentrations are almost entirely determined by GFR.

A number of factors influence urea formation, including liver function, protein intake, and protein catabolism rate. Urea excretion is also influenced by hydration status, the amount of water reabsorption, and GFR.

A high serum creatinine level, as well as a urine output of less than 10 mL/hour and the production of concentrated looking urine, do not necessarily indicate a specific cause of oliguria.

The statement Epinephrine is formulated as 1 in 1000 solution means 1 gm epinephrine is present in 1000 ml of solution.

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

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

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

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

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

Glycolysis occurs in the cytoplasm of the cell. It converts 1 glucose molecule (6-carbon) to pyruvate (two 3-carbon molecules) and produces 4 ATP molecules and 2NADH but uses 2 ATP in the process with an overall net energy production of 2 ATP.

Pyruvate is then oxidised to acetyl coenzyme A (generating 2 NADH per pyruvate molecule). This takes place in the mitochondria and then enters the Krebs cycle (citric acid cycle). It produces 2 ATP, 8 NADH and 2 FADH2 per glucose molecule.

Electron transport phosphorylation takes place in the mitochondria. The aim of this process is to break down NADH and FADH2 and also to pump H+ into the outer compartment of the mitochondria. It produces 32 ATP with an overall net production of 36ATP.

In anaerobic respiration which occurs in the cytoplasm, pyruvate is reduced to NAD producing 2 ATP.

Dabigatran template is a prodrug and its active metabolite is a direct thrombin inhibitor. It is a synthetic, reversible, non-peptide thrombin inhibitor. This inhibition of thrombin results in a decrease of fibrin and reduces platelet aggregation.

Drugs like warfarin act by inhibiting the activation of vitamin K-dependent clotting factors. These factors are synthesized by the liver and activated by gamma-carboxylation of glutamate residues with the help of vitamin K. Hydroquinone form of vitamin K is converted to epoxide form in this reaction and regeneration of hydroquinone form by enzyme vitamin K epoxide reductase (VKOR) is required for this activity. Oral anticoagulants prevent this regeneration by inhibiting VKOR, thus vitamin K-dependent factors are not activated. These factors include clotting factors II, VII, IX, and X as well as anti-clotting proteins, protein C and protein S.

The pituitary gland plays a crucial role in the neuro-endocrine axis. It is located at the base of the skull in the sella turcica of the sphenoid bone. It is connected superiorly to the hypothalamus, third ventricle, and visual pathways, and laterally to the cavernous sinuses, internal carotid arteries, and cranial nerves III, IV, V, and VI.

Pituitary tumours make up about 10-15% of all intracranial tumours. The majority of adenomas are benign. Over-secretion of pituitary hormones (most commonly prolactin, growth hormone, or ACTH), under-secretion of hormones, or localised or generalised pressure effects can all cause symptoms.

Compression of the optic chiasm can result in visual field defects, the most common of which is bitemporal hemianopia. This is caused by compression of the nasal retinal fibres, which carry visual impulses from temporal vision across the optic chiasm to the contralateral sides before continuing to the optic tracts.

The interruption of the visual pathways distal to the optic chiasm causes a homonymous visual field defect. The loss of the right or left halves of each eye’s visual field is referred to as homonymous hemianopia. It’s usually caused by a middle or posterior cerebral artery territory stroke that affects the occipital lobe’s optic radiation or visual cortex.

Binasal hemianopia is a condition in which vision is lost in the inner half of both eyes (nasal or medial). It’s caused by compression of the temporal visual pathways, which don’t cross at the optic chiasm and instead continue to the ipsilateral optic tracts. Binasal hemianopia is a rare complication caused by the internal carotid artery impinging on the temporal (lateral) visual fibres.

A monocular visual loss (that is, loss of vision in only one eye) can be caused by a variety of factors, but if caused by nerve damage, the damage would be proximal to the optic chiasm on the ipsilateral side.

A central scotoma is another name for central visual field loss. Every normal mammalian eye has a scotoma, also known as a blind spot, in its field of vision. The optic disc is a region of the retina that lacks photoreceptor cells and is where the retinal ganglion cell axons that make up the optic nerve exit the retina. When both eyes are open, visual signals that are absent in one eye’s blind spot are provided for the other eye by the opposite visual cortex, even if the other eye is closed.

Scotomata can be caused by a variety of factors, including demyelinating disease such as multiple sclerosis, damage to nerve fibre layer in the retina, methyl alcohol, ethambutol, quinine, nutritional deficiencies, and vascular blockages either in the retina or in the optic nerve.

Bilateral scotoma can occur when a pituitary tumour compresses the optic chiasm, causing a bitemporal paracentral scotoma, which then spreads out to the periphery, causing bitemporal hemianopsia. A central scotoma in a pregnant woman could be a sign of severe pre-eclampsia.

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.

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.

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

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

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

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

Smoking is a major risk factor associated with perioperative respiratory and cardiovascular complications. Evidence also suggests that cigarette smoking causes imbalance in the prostaglandins and promotes vasoconstriction and excessive platelet aggregation. Two of the constituents of cigarette smoke, nicotine and carbon monoxide, have adverse cardiovascular effects. Carbon monoxide increases the incidence of arrhythmias and has a negative ionotropic effect both in animals and humans.

Smoking causes an increase in carboxyhaemoglobin levels, resulting in a leftward shift in which appears to represent a risk factor for some of these cardiovascular complications.

There are two mechanisms responsible for the leftward shift of oxyhaemoglobin dissociation curve when carbon monoxide is present in the blood. Carbon monoxide has a direct effect on oxyhaemoglobin, causing a leftward shift of the oxygen dissociation curve, and carbon monoxide also reduces the formation of 2,3-DPG by inhibiting glycolysis in the erythrocyte. Nicotine, on the other hand, has a stimulatory effect on the autonomic nervous system. The effects of nicotine on the cardiovascular system last less than 30 min.

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

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

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

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

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

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

Step 3 (Ten minutes after step 2)

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

Step 4 (20 minutes after step 3)

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

Tonic-clonic (Grand mal) epilepsy is characterised by a general loss of consciousness with violent involuntary muscle contractions.

The NICE guidelines for treatment indicates the use of sodium valproate and lamotrigine, but sodium valproate unsuitable in this case and she is a woman of reproductive age and it is known to have teratogenic effects. Lamotrigine is a more suitable choice, prescribed as 800mg daily.

NICE guidelines also advice an additional prescription of 5mg of folic acid daily for women on anticonvulsant therapy looking to get pregnant. It also warns of the need for extra contraceptive precaution as there is a possibly that the anticonvulsant agent can reduce levels of contraceptive agents.

Stimulation of the vagal nerve stimulation is only necessary in patients who are refractory to medical treatment and not candidates for surgical resection.

The formula for calculating air: oxygen entrainment ratio is given as :
100% − FiO2 = air/oxygen entrainment ratio
Since FiO2 − 21% and the entrainment ratio is already known. Substituting the values in the equation: x = FiO2.

100 − x = 9
x − 21
100 − x = 9(x − 21)
100 − x = 9x − 189
10x = 289
x = 289/10
x = 28.9%

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

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

Multiple regression analysis revealed that velocity of lactate accumulation (VOBLA) accounted for 92 percent of the variation in marathon running velocity (VM), and VOBLA plus training volume prior to the marathon accounted for 96 percent of the variation. Percent ST muscle fibre distribution (r = 0.55-0.69) and capillary density (r = 052-0.63) were found to be positively correlated with all performance variables. As a result, marathon running performance was linked to VOBLA and the ability to run at a pace close to it during the race. The percent ST, capillary density, and training volume were all related to these properties.

Another metabolic adaptation compared to normal people is the early selection of fat for oxidation by muscle, especially when glucose availability is limited during high-intensity exercise. This helps to delay the onset of muscle fatigue, but it does not prevent VOBLA.

For a given level of exercise, training can also result in cardiovascular adaptation, such as increased heart size, increased contractility, and a slower heart rate. All of these factors contribute to an increase in maximal oxygen consumption (VO2 max), but genetic factors, despite intensive training, play a large role in an athlete’s performance.

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

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

Professor Mapleson classified non-rebreathing circuits based on the position of the APL valve, which controls fresh gas flow.

The Mapleson A (Magill) circuit is most effective in spontaneous breathing, requiring only 70-100 ml/kg (the patient’s minute volume) of fresh gas flow. The patient inhales fresh gas from the reservoir bag and tubing during inspiration. During expiration, the patient adds dead space gas (gas that hasn’t been exchanged) to the tubing and reservoir bag in addition to the fresh gas flow. At the patient’s end, alveolar gas is vented through the APL valve. During the expiratory pause, the fresh gas flow causes more gas to be released.

The Mapleson A is inefficient during controlled ventilation. Venting occurs during inspiration rather than during the expiratory phase, as it does during spontaneous ventilation. As a result, unless a high fresh gas flow of >20 L/minute is used, alveolar gas is rebreathed.

During spontaneous ventilation, the Mapleson D circuit is inefficient.

The oxygen concentration in a Hudson mask is insufficient to allow for adequate pre-oxygenation.

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.

The minimal alveolar concentration (MAC) is the concentration of an inhalation anaesthetic agent in the lung alveoli required to stop a response to the surgical stimulus in 50% of the patient.

Following factors don’t affect the MAC of the inhaled anaesthetic agents:

Gender, acidosis, alkalosis, hypothyroidism, hyperthyroidism, body weight, serum potassium level, and the duration of the anaesthesia.

MAC increase in children, elevated temperature, high metabolic rate, sympathetic increase and chronic alcoholism.

MAC decrease in low temperature, low oxygen level, old age, hypotension (<40 mmHg), depressant drugs e.g. opioids and low level of catecholamines; alpha methyl dopa. Carbon dioxide O2 at the pressure > 120mmHg is being used in anesthetic-Hinkman as an additive effect to decrease MAC, however, increase concentration of CO2 activates the sympathetic system resulting the MAC increases.

The oxygen consumption rate (VO2) at rest is 3.5 ml/kg/minute (one metabolic equivalent or 1 MET).
3.86 ml/kg/minute thyrotoxicosis

Young children consume a lot of oxygen: around 7 ml/kg/min when they are born. The metabolic cost of breathing is higher in children than in adults, and it can account for up to 15% of total oxygen consumption. Similarly, an infant’s metabolic rate is nearly twice that of an adult, resulting in a larger alveolar minute volume and a lower FRC.

At term, oxygen consumption at rest can increase by as much as 40% (5 ml/kg/minute) and can rise to 60% during labour.

When compared to normal basal metabolism, sepsis syndrome increases VO2 and resting metabolic rate by 30% (4.55 ml/kg/minute). In septicaemic shock, VO2 decreases.

Dobutamine hydrochloride was infused into 12 healthy male volunteers at a rate of 2 micrograms per minute per kilogramme, gradually increasing to 4 and 6 micrograms per minute per kilogramme. Dobutamine was infused for 20 minutes for each dose. VO2 increased by 10% to 15%. (3.85-4.0 ml/kg/min).

Nausea and vomiting occur commonly due to Chemoreceptor Trigger Zone (CTZ) stimulation by dopamine (Domperidone but not metoclopramide can be used for the treatment of this vomiting)

Dopamine itself cannot cross the blood-brain barrier (BBB) but its precursor levodopa can cross BBB.

Dopamine can modulate extrapyramidal symptoms like acute dyskinesia, tardive dyskinesia, Parkinsonism, and Neuroleptic malignant syndrome.

Dopamine inhibits the secretion of prolactin from the pituitary gland.

Oxygen delivery is related to blood flow as most of the oxygen binds to haemoglobin in red blood cells, although a small amount is dissolved in the plasma. Blood flow per 100 g of tissue is greatest in the kidneys.

The following is the oxygen consumption rate of different organs in ml/minute/100g

Hepatoportal = 2.2
Kidney = 6.8
Brain = 3.7
Skin = 0.38
Skeletal muscle = 0.18
Heart = 11

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.

Midazolam is the benzodiazepine in question. It’s the only benzodiazepine that undergoes tautomeric transformation (dynamic isomerism). The molecule is ionised and water soluble at pH 3.5, but when injected into the body at pH 7.4, it becomes unionised and lipid soluble, allowing it to easily pass through the blood brain barrier.

The half-life of midazolam is only 2-4 hours.

It is a GABAA receptor agonist because it is a benzodiazepine. GABAA receptors are found in abundance throughout the central nervous system, particularly in the cerebral cortex, hippocampus, thalamus, basal ganglia, and limbic system. GABAA receptors are ligand-gated ion channels, with the inhibitory neurotransmitter gamma-aminobutyric acid as the endogenous agonist. It is a pentameric protein (2, 2 and one subunit) that spans the cell membrane, and when the agonist interacts with the alpha subunit, a conformational change occurs, allowing chloride ions to enter the cell, resulting in neuronal hyperpolarization.

For status epilepticus, midazolam is not the drug of choice. Lorazepam is the benzodiazepine of choice for status epilepticus.

The middle cerebral artery is a part of the circle of Willis system of anastomosis within the brain, and the most often affected by brain pathology.

The primary function of the middle cerebral artery is providing oxygenated blood to related regions of the brain. It achieves this by giving off different branches to supply different brain regions, namely:

The cortical branches: which supplies the primary motor and somatosensory cortical areas of some parts of the face, trunk and upper limbs.

The small central branches: which supply the basal ganglia and internal capsule via the lenticulostriate vessels.

The superior division: which supplies the lateral inferior frontal lobe, including the Broca area which is responsible for production of speech, language comprehension, and writing.

The inferior division: which supplies the superior temporal gyrus, including Wernicke’s area which controls speech comprehension and language development.

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

Skeletal muscle blood flow is in the range of 1-4 ml/min per 100 g when at rest. Blood flow can reach 50-100 ml/min per 100 g during exercise. With maximal vasodilation, blood flow can increase 20 to 50 times.

The adrenal medulla releases catecholamines and increases neural sympathetic activity during exercise. Normally, alpha-1 and alpha-2 would cause vasoconstriction in the muscle groups being used, but vasodilatory metabolites override these effects, resulting in a so-called functional sympathectomy. Local hypoxia and hypercarbia, nitric oxide, K+ ions, adenosine, and lactate are some of the stimuli that cause vasodilation.

However, the splanchnic and cutaneous circulations, which supply inactive muscles, vasoconstrict.

Sympathetic cholinergic innervation of skeletal muscle arteries is found in some species (such as cats and dogs, but not humans). Vasodilation is induced by stimulating smooth muscle beta-2 adrenoreceptors, but at rest, the alpha-adrenoreceptor effects of adrenaline and noradrenaline predominate. During exercise, the skeletal muscle pump promotes venous emptying, but it does not necessarily increase blood flow.

Standard wire gauge cannulas for intravenous and intraarterial use are available (SWG or G). The SWG is a former imperial unit (which requires metric conversion). The cross sectional area of wires is becoming more popular as a size measurement.

The number of wires that will fit into a standard hole template is referred to as SWG.

This standard sized hole can accommodate 22 thin wires side by side (each wire the diameter of a 22 gauge cannula)
In the same hole, 14 thicker wires would fit (each wire the diameter of a 14 gauge cannula)

While the diameter and thus radius of a parallel sided tube are the most important determinants of fluid flow rate, they are not commonly used to compare cannula sizes.

The circumference of French gauge (FG) catheters (urinary or chest drains) is measured. Sizes of double lumen tracheal tubes are FG. Internal diameter is used to measure single lumen tubes.

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 normal peak inspiratory flow in healthy individuals is 20-30 L/min during each normal tidal ventilation. This is expected to increase with greater respiratory rate and deeper inspiration.

Face masks are used to facilitate the delivery of oxygen from a breathing system to a patient. Face masks can be divided into two types: fixed performance or variable performance devices.

In fixed performance devices (also known as high air flow oxygen enrichment or HAFOE), fixed inspired oxygen concentration is delivered to the patent, independent and greater than that of the patient’s peak inspiratory flow rate (PIFR). No random entrainment is expected to occur at the time of PIFR, hence, the oxygen concentration in HAFOE devices is not dependent on the patient’s respiratory pattern.

Moreover, in HAFOE masks, the concentration of oxygen at a given oxygen flow rate is determined by the size of the constriction; a device with a greater entrainment aperture delivers a lower oxygen concentration. Therefore, a 40% Venturi device will have lesser entrainment aperture when compared to a 31% Venturi. Venturi masks allow relatively fixed concentrations of supplemental oxygen to be inspired e.g. 24%, 28%, 31%, 35%, 40% and 60% oxygen. These are colour coded and marked with the recommended oxygen flow rate.

Variable performance devices deliver variable inspired oxygen concentration to the patient, and is dependent on the PIFR. The PIFR can often exceed the flow rate at which oxygen or an oxygen/air mixture is supplied by the device, depending on a patient’s inspiratory effort. In addition, these masks allow expired air to be released through the holes in the sides of the mask. Thus, with increased respiratory rate, rebreathing of alveolar gas from inside the mask may occur.

The axillary nerve lies behind the axillary artery initially, and in front of the subscapularis. It passes downward to the lower border of the subscapularis muscle.

In company with the posterior humeral circumflex artery and vein, it winds backward through a quadrilateral space bounded above by the subscapularis (anterior) and teres minor (posterior), below by the teres major, medially by the long head of the triceps brachii, and laterally by the humerus (surgical neck).

It then divides into an anterior and a posterior part. The anterior division supplies the deltoid (anterior and middle heads) while the posterior division supplies the teres minor and posterior part of deltoid
The posterior division terminates as the superior lateral cutaneous nerve of the arm

The common peroneal (fibular) nerve descends obliquely along the lateral side of the popliteal fossa to the fibular head, medial to biceps femoris.

The sural nerve exits at the fossa’s lower inferolateral aspect and is more at risk in short saphenous vein surgery.

The tibial nerve lies more medially and is even less likely to be injured in this location.

The boundaries of the popliteal fossa are:
Superolateral – the biceps femoris tendon
Superomedial – semimembranosus reinforced by semitendinosus
Inferomedial and inferolateral – medial and lateral heads of gastrocnemius

The contents of the Popliteal fossa are:

1. The popliteal artery
2. The popliteal vein
3. The Tibial nerve and common Fibular nerve
4. Posterior femoral cutaneous nerve: descends and pierces the roof
5. Small saphenous vein
6. popliteal lymph nodes
7. fat

The nerve stimulators deliver a stimulus lasting for 1-2 milliseconds (not second) to perform nerve blockage.

There are just 2 leads (not 3); one for the skin and other for the needle.

Prior to the administration of the local anaesthesia, a current of 0.25 – 0.5 mA (not 1-2mA) at the frequency of 1-2 Hz is preferred.

If the needle tip is close to the nerve, muscular contraction could be possible at the lowest possible current.

Insulated needles have improved the block success rate, as the current is only conducting through needle tip.

Stimulus to the femoral nerve which is placed in the mid lingual line causes withdrawer of the quadriceps and knee extension, that’s the dancing patella ( not plantar flexion).

Mixed venous oxygen content (CvO2) is the oxygen concentration in 100mL of mixed venous blood taken from the pulmonary artery. It is usually 12-17 mL/dL (70-75%). It is represented mathematically as:

CvO2 = (1.34 x Hgb x SvO2 x 0.01) + (0.003 x PvO2)

Where,

1.34 = Huffner’s constant
Hgb = Haemoglobin level (g/dL)
SvO2 = % oxyhaemoglobin saturation of mixed venous blood
PvO2 = 0.0225 = mL of O2 dissolved per 100mL plasma per kPa, or 0.003 mL per mmHg

Therefore,

CvO2 = (1.34 x 10 x 70 x 0.01) + (0.003 x 50)

CvO2 = 9.38 + 0.15 = 9.53 mL/100mL

The coeliac axis refers to one of the splanchnic arteries located within the abdomen.

It arises from the aorta almost horizontally at the level of the T12 vertebrae

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

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

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

Rifampicin is a derivative of a rifamycin (other derivatives are rifabutin and rifapentine). It is bactericidal against both dividing and non-dividing mycobacterium and acts by inhibiting DNA-dependent RNA polymerase. Thus this drug inhibits RNA synthesis.

Mesenteric ischemia is ischemia of the blood vessels of the intestines. It can be life-threatening, especially if the small intestine is involved.

The inferior mesenteric artery originates 3-4 cm above the bifurcation of the abdominal aorta.
The left colic artery branches off the inferior mesenteric artery to supply the following:
– distal 1/3 of the transverse colon
– descending colon

At approximately the left colic flexure (splenic flexure), a transition occurs in the blood supply of the GI tract. The SMA supplies the proximal part to the flexure, and the IMA supplies the part distal to the flexure. This is why the left colic flexure is a watershed area and is prone to ischemia exacerbated by atherosclerotic changes or hypotension. The dominant arterial supply of the splenic flexure is usually from the left colic artery, but it may also get collaterals from the left branch of the middle colic artery.

The AMA and PMA do not exist.
The splenic artery directly supplies the spleen and has branches that supply the stomach and the pancreas.
The proximal two-thirds of the transverse colon is supplied by the middle colic artery, a branch of the SMA.

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.

Therapeutic index is a measure which relates the dose of a drug required to produce a desired effect to that which produces an undesired effect.

In humans, it is usually defined as the ratio of the toxic dose for 50% of the population (TD50) to the minimum effective dose for 50% of the population (ED50) for some therapeutically relevant effect. In animal studies, the therapeutic index can be defined as the ratio of the median lethal dose (LD50) to the ED50.

The starling forces operate to maintain a homeostatic flow across the pulmonary capillary bed.

The outward driving force comprises of the capillary hydrostatic pressure (13 mmHg), negative interstitial fluid pressure (zero to slightly negative), and interstitial colloid osmotic pressure (17 mmHg). The inward driving force is controlled by the plasma colloid osmotic pressure (25 mmHg).