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

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

A line connecting the greater trochanters is also incorrect.

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

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

Central cord syndrome is the most commonly occurring type of partial spinal cord lesion. It is more likely to occur in older patients with cervical spondylosis and a hyperextension injury. The injury to the spinal cord occurs in the grey matter causing the following symptoms:

Disproportionally higher motor function weakness in the upper limbs than in lower limbs
Dysfunction of the bladder
Degrees of sensory loss below the level of the lesion

An anterior spinal artery infarction will interrupt the corticospinal tract resulting in paralysis of motor function, loss of pain and temperature sensation, all occurring below the level of the injury.

Brown-Sequard syndrome occurs as a result of the hemisection of the spinal cord. Its symptoms include ipsilateral upper motor neurone paralysis and loss of proprioception, with contralateral loss of pain and temperature sensation.

Spinal cord infarctions rarely occur in the posterior spinal artery.

Cauda equina syndrome occurs as a result of compression of the lumbosacral spinal nerve roots below the level of the conus medullaris. Injury to these nerves will cause partial or complete loss of movement and sensation in this distribution.

T3 is produced by peripheral de-iodination of T4. It is more active than T4.

TBG, like most binding proteins, is increased in pregnancy. Because of this, measurement of free thyroid hormone concentration is more important than total.

T4 and T3 concentrations are decreased in Illness and starvation.

L-T4 that is the active molecule while D-T4 is inactive.

The metabolism of drugs in the liver occurs in 3 phases

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

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

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

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

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

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

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

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

Tetracyclines inhibit protein synthesis through reversible binding to bacterial 30s ribosomal subunits (not 50s) which prevent binding of new incoming amino acids (aminoacyl-tRNA) and thus interfere with peptide growth.

They penetrate macrophages and are thus a drug of choice for treating infections due to intracellular organisms.

Tetracycline does not inhibit transpeptidation. Meanwhile, it is chloramphenicol which is responsible for inhibiting transpeptidation.

Tetracycline can get deposited in growing bone and teeth due to its calcium-binding effect and thus causes dental discoloration and dental hypoplasia. Due to this reason, they should be avoided in pregnant or lactating mothers.

Simultaneous administration of aluminium hydroxide can impede the absorption of tetracyclines.

ANOVA is based upon within group variance (i.e. the variance of the mean of a sample) and between group variance (i.e. the variance between means of different samples). The test works by finding out the ratio of the two variances mentioned above. (Commonly known as F statistic).

The Tare weight of a cylinder is the weight when it is empty. So,

Weight of cylinder – tare weight = weight of remaining N2O (g).
4.44 kg – 4 kg = 0.44 kg
Here,
0.44 kg of nitrous oxide remains in the cylinder

Since the molecular weight of nitrous oxide is 44 g and one mole of an ideal gas will occupy a volume of 22.4 litres at STP
Therefore amount left in the cylinder is several (gN2O/44) x 22.4 litres of N2O.

(440/44) x 22.4 = 224 litres.

While the brain only weighs 3% of the body weight, 15% of the cardiac output goes towards the brain.

Between mean arterial pressures (MAP) of 60-130 mmHg, autoregulation of cerebral blood flow (CBF) occurs. Exceeding this, the CBF is maintained at a constant level. This is controlled mainly by the PaCO2 level, and the autonomic nervous system has minimal role.

Beyond these limits, the CBF is directly proportional to the MAP, not the systolic blood pressure.

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

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 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.

Ambient pressure has no effect on a volatile agent’s saturated vapour pressure (SVP). At a temperature of 20°C, the SVP of sevoflurane is approximately 21 kPa, or 21% of atmospheric pressure (100 kPa).

The SVP of sevoflurane remains the same when the ambient pressure is doubled to 200 kPa, but the output of the vaporiser is halved, now 21 percent of 200 kPa, equalling 10.5 percent. The vaporiser’s output has increased to 1%, but the partial pressure output has remained unchanged. The splitting ratio will not change because it is determined by temperature changes.

Calculations can be made as follows:

Vaporizer output % (ambient pressure) = % volatile (calibrated) x 100 kPa calibrated pressure/ambient pressure
2% = 2% (dialled) × 100/100
2% of 100 = 2 kPa

Altitude, pressure 50 kPa
4% = 2% (dialled) × 100/50
4% of 50 = 2 kPa

High pressure at 200 kPa
1% = 2% (dialled) × 100/200
1% of 200 = 2 kPa

Sevoflurane has a boiling point of 58°C and, unlike desflurane (which has a boiling point of 22.8°C), does not need to be heated and pressurised with a Tec 6 vaporiser.

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.

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

The intercostal nerves arise from the ventral rami of the first 11 thoracic spinal nerves. they course along the costal groove on the lower margin of the rib.

The twelfth intercoastal nerve is called the subcostal nerve. This is because it is below the 12th rib.

Each intercostal nerve is connected to a ganglion of the sympathetic trunk from which it carries preganglionic and postganglionic fibres that innervate blood vessels, sweat glands, and muscles.

The lateral and medial pectoral nerves innervates pectoralis major muscle.

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

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

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

The common hepatic artery arises from the celiac artery and has the following branches:
1. hepatic artery proper that branches into –
a. cystic artery to supply the gallbladder
b. left and right hepatic arteries to supply the liver
2. gastroduodenal artery that branches into
a. right gastroepiploic artery
b. superior pancreaticoduodenal artery
3. right gastric artery

The pancreatic artery is a branch of the splenic artery.

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

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.

A pulse oximeter is a piece of medical equipment used as a non-invasive method of measuring the oxygen saturation of blood.

It works by measuring the ratio of absorption of red and infrared light in a section of blood flow, as red light is largely absorbed by deoxygenated blood, and infrared light is largely absorbed by oxygenated blood.

Pulse oximetry relies on photoplethysmography (PPG) waveforms. The oximeter has 2 sides, with different functions. One side houses light-emitting diodes which are responsible for transmitting 2 light wavelengths, 660nm for red light and 940nm for near infrared light. The other side is a photodetector. The light emitted travels through the body and the amount that is not absorbed is measured by the photodetector.

Smokers often have increased levels of carboxy haemoglobin (COHb). This leads to artificial increases in pulse oximeter readings as it is unable to differentiate between COHb and oxyhaemoglobin (O2HB) as they both absorb red light at 660nm. Every 1% increase of circulating carboxyhaemoglobin, results in a correlative 1% increase in oximeter readings.

Prilocaine toxicity will cause an artificial decrease in oximeter readings. This is because prilocaine metabolites cause methemoglobinemia (MetHB), which are dysfunctional haemoglobins unable to properly transport oxygen. In this case, a laboratory multiwavelength co-oximeter is recommended for a more accurate reading.

Anaemia will not affect oximeter readings as long as haemoglobins in the blood are normal.

Sickle cell disease does not affect oximeter readings despite its ability to cause hypoxia and shift the oxygen dissociation curve to the right.

Brown-red fingernail polish will cause an underestimation of pulse oximeter readings.

The functional residual capacity (FRC) is the volume in the lungs at the end of passive expiration. It is determined by opposing forces of the expanding chest wall and the elastic recoil of the lung. A normal FRC = 1.7 to 3.5 L. It a marker for lung function, and, during this time, the alveolar pressure is equal to the atmospheric pressure.

FRC cannot be measured by spirometry because it contains the residual volume.

Tidal volume, inspiratory reserve volume, forced expiratory volume in 1 second, and vital capacity can be measured directly.

A Wrights Respirometer measures the volume of air exhaled over the course of one minute of normal breathing

It is unidirectional and measures tidal volume and minute volume of gas flow in one direction. It is placed at the expiratory side (lower pressure than inspiratory side therefore lower chances of gas leaks)

Slits are arranged such that incoming gas will rotate the vane at a rate of 150 revolutions per litre of flowing gas

The Wright respirometer tends to over-read at high flow rates and under-read at low flows because of mechanical causes like friction and inertia and the accumulation of water vapour

The ideal flow for accurate readings is 2 L/min for the respirometer. The respirometer reads the tidal volume and minute volume with a ±5–10% accuracy within the range of 4–24 L/min.

The external laryngeal nerve arises from the superior laryngeal nerve and provides innervation to the cricothyroid muscle.

The other muscles mentioned receive their innervations from the recurrent laryngeal nerve.

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

Any attempt to retrieve lodged foreign objects must be done careful as there is also a high risk of damage during this process.

The other mentioned nerves are not at risk of being affected.

Oxytocin is structurally similar to Antidiuretic Hormone (ADH) and thus oxytocin can cause water intoxication (due to an ADH like action)

Oxytocin is secreted by the posterior pituitary along with ADH. It increases uterine contractions – the contraction of the upper segment (fundus and body) of the uterus whereas the lower segment is relaxed facilitating the expulsion of the foetus

Antidiuretic hormone (ADH) also called vasopressin is released from the posterior pituitary in response to hypertonicity and increases fluid reabsorption from the kidney.

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

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

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

The hindgut is from the distal third of the transverse colon down to the upper one-third of the anal canal. The inferior mesenteric artery supplies the hindgut.

The inferior mesenteric artery arises from the aorta behind the inferior border of the third part of the duodenum 3–4 cm above the aortic bifurcation, at the third lumbar vertebra level.

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

Variance and standard deviation indicate the dispersion of the plot from mean value and thus are not really helpful in summarizing the mean.

Range is the difference between maximum and minimum value that is 45 in this case.

The mean in this case is 6.2 due to the presence of an outlier 45. In the presence of outlier mean can be misleading as it is quite sensitive to skewness in data.

Mode is the most frequent value. In this case mode has 4 values: 0,1,2,4.

In case of skewedness, median is the most apt representative of the mean as it is not affected by outliers. In this case since the data set has even values i.e. 10. Median is the average of the 5th & 6th entry after arranging the data in ascending order like that in case of the question (0,0,1,1,2,2,3,4,4,45). This turns out to be 2.

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

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

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

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

Adenosine receptors are expressed on the surface of most cells.
Four subtypes are known to exist which are A1, A2A, A2B and A3.

Of these, the A1 and A2 receptors are present peripherally and centrally. There are agonists at the A1 receptors which are antinociceptive, which reduce the sensitivity to a painful stimuli for the individual. There are also agonists at the A2 receptors which are algogenic and activation of these results in pain.

The role of adenosine and other A1 receptor agonists is currently under investigation for use in acute and chronic pain states.

The National Institute for Health and Care Excellence (NICE) has published guidelines on infective endocarditis prophylaxis (IE). The goal was to create clear guidelines for antibiotic prophylaxis in patients undergoing dental procedures as well as certain non-dental interventional procedures. A number of studies have found an inconsistent link between recent interventional procedures and the development of infective endocarditis in both dental and non-dental procedures.

Antibiotic prophylaxis against infective endocarditis is not advised or required in the following situations:

Dental patients undergoing procedures
Patients undergoing procedures involving the upper and lower gastrointestinal tracts, the genitourinary tract (including urological, gynaecological, and obstetric procedures, as well as childbirth), and the upper and lower respiratory tract (including ear, nose and throat procedures and bronchoscopy).

Antibiotic resistance can be exacerbated by the indiscriminate use of prophylactic antibiotics, but this is not the primary reason for avoiding their use in these situations.

To reduce the risk of endocarditis, any patient who is at risk of developing IE should be investigated and treated as soon as possible. Patients with the following conditions are at risk of developing IE:
acquired valvular heart disease with regurgitation or stenosis
previous valve replacement
structural congenital heart disease
past history of IE, or
hypertrophic cardiomyopathy (HOCM)

It would also be appropriate for high-risk dental procedures and those with severe gingival disease.

Although this patient may not have structural heart disease, ABs should be administered on a case-by-case basis.

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

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

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

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

The needle should be inserted just below the skin at the mid inguinal point which is the surface indicator for the femoral artery.

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

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

The emulsification and absorption of fats requires Bile salts.

Absorption of fats is associated with the activation of lipases in the intestine.

Bile salts are involved in fat soluble vitamin absorption and are reabsorbed in the terminal ileum (B12 is NOT fat soluble).

Although Vitamin B12 is also absorbed in the terminal ileum, it is a water soluble vitamin (as are B1, nicotinic acid, folic acid and vitamin C) .

The gastric parietal cells secretes Intrinsic factor that is essential for the absorption of B12.

Patients who have sustained thermal injuries are at high risk of becoming hypercatabolic with larger cardiac outputs and oxygen consumptions.

The hypermetabolic states increase with an increase in the burn severity and surface area of the skin affected. A patient with thermal injuries affecting 60% of the total surface area of the body will have twice the normal metabolic rate.

The optimal temperature for nursing patients with burn injuries is 30°C to conserve the energy usage. The areas affected by the burn injuries should be covered to reduce loss of fluid via evaporation. Resetting hypothalamic thermoregulation will cause a 1-2°C increase in core temperature.

Burn injuries will have an immediate effect on the intestine, destroying the barrier function and allowing for the movement of bacteria and endotoxins within hours.

Enteral nutrition allows for the delivery of nutrients directly to the stomach or intestine. It has correlation with a dampened hypermetabolic response to a thermal and injury, especially when initiated early as it helps to protect the integrity of the mucosal lining and prevents the movement of bacteria into circulation.

Diet changes have been linked to reduced mortality due to burn injuries. Diets high in protein especially (calorie: nitrogen ratio of 100: 1), have the highest correlation with improved survival rates.

Parenteral feeds may be required alongside enteral nutrition, even with the increased risks of infection.

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.

The external iliac artery is the larger of the two branches of the common iliac artery. It forms the main blood supply to the lower limbs. The common iliac bifurcates into the internal and external iliac artery anterior to the sacroiliac joint.

The external iliac artery courses on the medial border of the psoas major muscles and exits the pelvic girdle posterior to the inguinal ligament. Here, midway between the anterior superior iliac spine and the pubic symphysis, the external iliac artery becomes the femoral artery and descends along the anteromedial part of the thigh in the femoral triangle.

The pectineus forms the posterior border of the femoral canal.
The femoral vein forms the lateral border of the femoral canal.
The medial border of the adductor longus muscle forms the medial wall of the femoral triangle.
The medial border of the sartorius muscle forms the lateral wall of the femoral triangle.

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

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

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

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

The extrinsic pathway is best assessed by the PT time.

D-dimer is a fibrin degradation product which is raised in the presence of blood clots.

A 50:50 mixing study is used to assess if a prolonged PT or aPTT is due to factor deficiency or a factor inhibitor.

The thrombin time is a test used to assess fibrin formation from fibrinogen in plasma. Factors that prolong the thrombin time include heparin, fibrin degradation products, and fibrinogen deficiency.

Intrinsic pathway – Best assessed by APTT. Factors 8,9,11,12 are involved. Prolonged aPTT can be seen in haemophilia and use of heparin.

Extrinsic pathway – Best assessed by Increased PT. Factor 7 involved.

Common pathway – Best assessed by APTT & PT. Factors 2,5,10 involved.

Vitamin K dependent factors are factors 2,7,9,10

The ureter runs anterior to the vertebrae at the level of L2 to L5, and stones are usually seen at these points on x-ray.

They can also be seen at the level of the sacro-iliac joints.

The null hypothesis states that there is no significant difference between two groups.

The alternative hypothesis states that there is a significant difference between two groups.

A type I error (false positive) occurs when a null hypothesis is rejected when it should be accepted.

A type II error (false negative) occurs when the alternative hypothesis is rejected when it should be accepted.

The probability determines the rejection of a null hypothesis.

The level of significance is set at p <0.05.

The laryngeal folds are comprised of two types of folds; the vestibular fold and the vocal fold. The vocal folds are mobile, and concerned with voice production. They are formed by the mucous membrane covering the vocal ligament. They are avascular, hence, are white in colour.

The internal branch of the superior laryngeal nerve provides sensation above the vocal cords. Lesions to this nerve may lead to loss of sensation above the vocal cords and loss of taste on the epiglottis.

The recurrent laryngeal nerve supplies the lateral and posterior cricoarytenoid, the thyroarytenoid. It also provides sensation below the vocal cords. Lesions to this nerve may cause respiratory obstruction, hoarseness, inability to speak and loss of sensation below the vocal cords.

The external branch of the superior laryngeal nerve supplies the cricothyroid muscle.

The glossopharyngeal nerve contains both sensory and motor components, and provides somatic innervation to the stylopharyngeus muscle, visceral motor innervation to the parotid gland, and carries afferent sensory fibres from the posterior third of the tongue, pharynx and tympanic cavity.

Adrenaline acts on ?1, ?2,?1, and ?2 receptors and also on dopamine receptors (D1, D2) and have sympathomimetic effects.

Natural catecholamines are Adrenaline, Noradrenaline, and Dopamine

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

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

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

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

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

The above mentioned patient presentation is one of an acute coronary syndrome.

The elevations noted in the ST-segments of multiple heart leads on ECG is diagnostic of an ST-elevation myocardial infarction.

The pulmonary artery branches to give rise to the right and left pulmonary arteries, which supply deoxygenated blood to the right and left lungs from the right ventricle.

The pulmonary veins do not form any bifurcations, and therefore do not give rise to any vessels. They travel to the left atrium from the lungs, carrying oxygenated blood.

The descending aorta continues from the aortic arch, and bifurcates to give off many branches, including the right and left common iliac arteries.

The coronary sinus is formed from the combination of four coronary veins, receiving blood supply from the great, middle, small and posterior cardiac veins, and transporting this venous blood into the right atrium.

The right and left aortic sinus give rise to the right and left coronary arteries, respectively. They branch of the ascending aorta, in the area just superior to the aortic valve.

The duodenojejunal flexure is the point where the duodenum becomes the jejunum.

The ligament of Treitz, which arises from the right crus of diaphragm, provides suspension for support.

Between the ileum and the caecum is the ligament of Treves.

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

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

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

The response of cerebral blood flow (CBF) to hyperoxia (PaO2 >15 kPa, 113 mmHg), the cerebral oxygen vasoreactivity is less well defined. A study originally described, using a nitrous oxide washout technique, a reduction in CBF of 13% and a moderate increase in cerebrovascular resistance in subjects inhaling 85-100% oxygen. Subsequent human studies, using a variety of differing methods, have also shown CBF reductions with hyperoxia, although the reported extent of this change is variable. Another study assessed how supra-atmospheric pressures influenced CBF, as estimated by changes in middle cerebral artery flow velocity (MCAFV) in healthy individuals. Atmospheric pressure alone had no effect on MCAFV if PaO2 was kept constant. Increases in PaO2 did lead to a significant reduction in MCAFV; however, there were no further reductions in MCAFV when oxygen was increased from 100% at 1 atmosphere of pressure to 100% oxygen at 2 atmospheres of pressure. This suggests that the ability of cerebral vasculature to constrict in response to increasing partial pressure of oxygen is limited.

Increases in arterial blood CO2 tension (PaCO2) elicit marked cerebral vasodilation.

CBF increases with general anaesthesia, ketamine anaesthesia, and hypoviscosity.

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).

The following are the pharmacokinetic properties of drugs with a low hepatic extraction ratio:

Changes in liver blood flow have no effect on drug clearance.
When given orally, drug clearance is extremely sensitive to changes in protein binding, intrinsic metabolism, and excretion, and there is no first-pass metabolism.

Warfarin and phenytoin are two drugs with low hepatic extraction ratios.

The following are the pharmacokinetic properties of drugs with a high hepatic extraction ratio:

When taken orally, undergo extensive first-pass metabolism; drug clearance is dependent on liver blood flow, and drug clearance is less sensitive to changes in protein binding and intrinsic metabolism.

Morphine, lidocaine, propranolol, and etomidate are examples of drugs with high hepatic extraction ratios.

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

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

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

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

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

The deep inguinal ring lies approximately 1.5-2cm above the midpoint of the inguinal ligament, the halfway point between the anterior superior iliac spine and the pubic tubercle, next to the epigastric vessels.

It is an important point in determining the nature of an inguinal hernia (direct or indirect). The patient is asked to cough after the hernia is reduced, with pressure applied to the deep inguinal ring. The hernia reappearing indicates it is direct, moving through the posterior wall of the inguinal canal.

Inferior and lateral to the pubic tubercle is the normal anatomical position of the neck of a femoral hernia.

Superior and medial to the pubic tubercle is the site of the superficial inguinal ring, and the normal anatomical position of the neck of an inguinal hernia.

The mid-inguinal point is located halways between the pubic symphysis and the anterior superior iliac spine. It is the surface marking for taking the femoral pulse.

Coronary perfusion pressure(CPP), the difference between aortic diastolic pressure (Pdiastolic) and the left ventricular end-diastolic pressure (LVEDP), is mainly determined by the formula:

CPP = Pdiastolic -LVEDP
where
Pdiastolic is the lowest pressure in the aorta before left ventricular ejection and
LVEDP is measured directly during a cardiac catheterisation or indirectly using a pulmonary artery catheter. The pulmonary artery occlusion or wedge pressure approximates best with LVEDP.

Using this patient’s haemodynamic data:

CPP = Pdiastolic – MPAWP
COO = 70 – 12 = 58mmHg

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

Mild 70-80%
Moderate 60-69%
Moderately severe 50-59%
Severe 35-49%
Very severe <35% This patient has a mixed deficit with a severe obstructive deficit as %FEV1/FVC predicted is 46.9% and a moderate restrictive deficit as %FVC of predicted is 61.3 FEV1/FVC ratio 80% < predicted and VC < 80% = mixed picture. FEV1/FVC ratio 80% < predicted and VC > 80% = obstructive picture.

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

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

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

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

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

Acidaemia, hypotension, and hyperthermia can all exacerbate toxicity.

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

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

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

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

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

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

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

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

Osmolarity refers to the osmotic pressure generated by the dissolved solute molecules in 1 L of solvent. Measurements of osmolarity are temperature dependent because the volume of the solvent varies with temperature. The higher the osmolarity of a solution, the more it attracts water from an opposite compartment.

Osmolarity can be computed using the following formulas:

Osmolarity = Concentration x number of dissociable particles; OR
Plasma osmolarity (Posm) = 2([Na+]) + (glucose in mmol/L) + (BUN in mmol/L)

Posm = 2 (144) + 3.5 + 9.5 = 301 mOsm/L

Suppose there is electrical neutrality, the formula will double the cation activity to account for the anions.

Plasma osmolarity (Posm) = 2([Na+] + [K+]) + (glucose in mmol/L) + (BUN in mmol/L)

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

The volume expired in the first second of maximal expiration after a maximal inspiration is known as forced expiratory volume in one second (FEV1), and it indicates how quickly full lungs can be emptied. It is the most commonly measured parameter for bronchoconstriction assessment.

The maximum volume of air exhaled after a maximal inspiration is known as the ‘slow’ vital capacity (VC). VC is normally equal to FVC after a forced vital capacity (FVC) or slow vital capacity (VC) manoeuvre, unless there is an airflow obstruction, in which case VC is usually higher than FVC.

The FEV1/FVC (Tiffeneau index) is a clinically useful index of airflow restriction that can be used to distinguish between restrictive and obstructive respiratory disorders.

The average expired flow over the middle half (25-75 percent) of the FVC manoeuvre is the forced expiratory volume (FEF25-75). The airflow from the resistance bronchioles corresponds to this. It’s a more sensitive indicator of mild small airway narrowing than FEV1, but it’s difficult to tell if the VC (or FVC) is decreasing or increasing.

The maximum expiratory flow rate achieved is called the peak expiratory flow (PEF), which is usually 8-14 L/second.

Number needed to treat is a measure of the impact of a treatment or intervention that is often used to communicate results to patients, clinicians, the public and policymakers. It states how many patients need to be treated for one additional patient to experience an adverse outcome (e.g. a death).

It is calculated as the inverse of the absolute risk reduction and is rounded to the next highest whole number.

The absolute risk reduction is 8% (16% – 8%). 100/8 = 12.5, so rounding up the next integer this gives at NNT of 13. i.e. you would need to give the new drug to 13 people to ensure that you prevented one death.

Closing capacity refers to volume of gas within the lungs at which the conducting small airways begin to close, that is, the point during expiration when small airways close.

It is calculated mathematically as:

Closing capacity = Closing volume (CV) + Residual volume (RV)

Functional residual capacity (FRC) is the volume of gas still present within the lungs post expiration.

Closing capacity is lower than the functional residual capacity in younger adults, but begins to rise to eventually equal, and then exceed it with increasing age (at about middle age), increasing intrabdominal pressure, decreasing blood flow in the pulmonary system and parenchymal disease within the pulmonary system.

A thermocouple, or a thermal junction, is temperature measuring device consisting of a pair of dissimilar metal (bimetallic) wires or strips joined together. Typically, copper and constantan (an alloy of 55% copper and 45% nickel) are used. When there is contact between these metals, a small voltage is generated in the order of millivolts. The magnitude of the thermojunction electromotive force (emf) is proportional to applied temperature (the Seebeck effect). This physical principle is applied in the measurement of temperature. The electromotive force at the measuring junction is proportional to temperature.

Two wires with different coefficients of expansion, joined together, can be used as a switch for thermostatic control.

Semiconductors are NOT used in thermocouple. The resistance of the measuring junction of a thermocouple is irrelevant.

All of the muscles of the larynx are innervated by the recurrent laryngeal nerve, except the cricothyroid muscle.

Cricothyroid muscle is located deep in the anterior neck, between the cricoid and thyroid cartilage and is innervated by the external laryngeal nerve. Any injury to this muscle can cause paralysis and lead to hoarseness. When cricothyroid muscle contracts, it leads to tightening, stretching and thinning of the vocal folds. This produces higher-pitched sounds during vocalization.

A patient experiencing hoarseness due to possible injury to the external laryngeal nerve should be reassured that the hoarseness will resolve in time due to increased compensation from the other muscles.

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

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

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

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

Heme a exists in cytochrome a and heme c in cytochrome c; they are both involved in the process of oxidative phosphorylation. 5′-Aminolevulinic acid synthase (ALA-S) is the regulated enzyme for heme synthesis in the liver and erythroid cells.

There are two forms of ALA Synthase, ALAS1, and ALAS2.

Among the breathing circuits, the Lack circuit is the most efficient for spontaneous breathing.

An outer coaxial tube is present to deliver fresh air; exhaust air is routed to an inner tube, which is then delivered to a scavenging system. An expiratory valve is seen at the patient end, which is an advantage over other circuits. Moreover, the Lack circuit prevents rebreathing slightly greater than the alveolar minute ventilation at 4-5 litres per minute.

The Bain circuit prevents rebreathing at 160-200ml/kg per minute, and is a co-axial version of the Mapleson D circuit.

The Mapleson E circuit prevent rebreathing at a fresh gas flow (FGF) of approximately twice the patient’s normal minute volume. A modification of this, the Mapleson F, has a reservoir bag at the opposite end for the FGF. This circuit is appropriate for paediatric patients with a body weight less than 20 kg.

The Delphi method relies on expert consensus. This method kicks off with an open ended questionnaire and uses its responses as a survey instrument for the next round in which each of the participants is asked to rate the items that the investigators have summarized on the basis of the data collected in the first round. Any disagreement is further discussed in phases to come on the basis of information obtained from previous phases.

The walls of the anterior nasal passage are supplied by the anterior ethmoidal branch of the nasociliary nerve, and the floor is innervated by the superior dental nerve (not the sphenopalatine nerves).

The walls and floor of the posterior nasal passage are innervated by the long and short sphenopalatine nerves and the great palatine nerve (not the superior dental nerves and the nasociliary nerve).

The vestibule is innervated by small branches of the infraorbital branch of the maxillary nerve.

The nasopharynx is innervated by the sensory branches of the trigeminal nerve (not the great palatine nerve).

The inflow of blood from the superior vena cava is directed towards the right atrioventricular orifice. It returns deoxygenated blood from all structures superior to the diaphragm, except the lungs and heart.

There are no valves in the superior vena cava which is why it is relatively easy to insert a CVP line from the internal jugular vein into the right atrium. The brachiocephalic vein is similar as it also has no valves.

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

Lidocaine 1% is formulated as 1000 mg/100 mL.

% solution is based on (grams of medicine) / 100 ml

% solution ~ (1000 mg) / 100 ml

% solution ~ 10 mg/ml

Examples:

• • Lidocaine 4% = 40 mg/ml of Lidocaine
  • Lidocaine 2% = 20 mg/ml of Lidocaine
  • Lidocaine 1% = 10 mg/ml of Lidocaine

The process used in the study is Delphi method. This method kicks off with an open ended questionnaire and uses its responses as a survey instrument for the next round in which each of the participants is asked to rate the items that the investigators have summarized on the basis of the data collected in the first round.

Any disagreement is further discussed in phases to come on the basis of information obtained from previous phases.

In any alveolar unit, the V/Q ratio affects alveolar oxygen (PAO2) and carbon dioxide tension (PACO2).

The partial pressure of alveolar carbon dioxide (PACO2) is plotted against the partial pressure of alveolar oxygen in a Ventilation-Perfusion (V/Q) ratio graph (PAO2). Given a set of model assumptions, the curve represents all of the possible values for PACO2 and PAO2 that an individual alveolus could have.

In the case of an infinity V/Q ratio (ventilation but no perfusion or dead space), the PACO2 of the alveolus will equal zero, while the PAO2 will approach that of external air (150mmmHg). At the apex of the lung, the V/Q ratio is 3.3, compared to 0.67 at the base.

PACO2 and PAO2 approach the partial pressures for these gases in the venous blood when the V/Q ratio is zero (no ventilation but perfusion). At the base of the lung, the V/Q ratio is 0.67, whereas at the apex, it is 3.3.

PAO2 at the apex is typically 132mmHg, and PACO2 is typically 28mmHg.

The average PAO2 at the base is 89 mmHg, while the average PACO2 is 42 mmHg.

Decreased stroke volume causes decreased ejection fraction which results in diastolic dysfunction.
Ejection fraction is not a useful measure in someone with diastolic dysfunction because stroke volume may be reduced whilst end-diastolic volume may be reduced.
Diastolic dysfunction may arise with reduced heart compliance.

Ejection fraction measures of the proportion of blood leaving the ventricles with each beat and is calculated as follows:
Stroke volume / end-diastolic volume.

A healthy ejection fraction is usually taken as 60% (based on a stroke volume of 70ml and end-diastolic volume of 120ml).

Respiratory inspiration causes a decreased pressure in the thoracic cavity, which in turn causes more blood to flow into the atrium.

Sitting up decreases venous because of the action of gravity on blood in the venous system.
Hypotension also decreases venous return.
A less compliant aorta, like in aortic stenosis increases end systolic left ventricular volume which decreases stroke volume.

Systemic vascular resistance = mean arterial pressure / cardiac output.
Increased vascular resistance impedes the flow of blood back to the heart.

Increased venous return increases end diastolic LV volume as there is more blood returning to the ventricles.

Boyle’s law is correctly stated as it states that the volume of a gas of known mass is inversely proportional with absolute pressure, at a constant temperature.

Beer’s law states that radiation absorption by a solution of known thickness and concentration is identical to that of a solution of double thickness and half concentration.

Bougner’s (or Lambert’s) law states that every layer with the same thickness will absorb the same amount of radiation as it passes through.

Graham’s law states that the diffusion rate of a gas is inversely related to the square root of its molecular weight.

Raoult’s law states that the reduction of a solvent’s vapour pressure is directly proportional to the solute’s molar concentration.

Cardiac conduction

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

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

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

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

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

The autonomic nervous system is divided into the sympathetic and parasympathetic nervous system. They are anatomically and physiologically different.

The sympathetic nervous system arises from the thoracolumbar outflow (T1-L5 ) at the lateral horns of grey matter of the spinal cord. Their preganglionic neurones are usually short myelinated and synapse in ganglia lateral to the vertebral column and have acetyl choline (Ach) as the neurotransmitter. Their postganglionic neurones are longer and unmyelinated and synapse with effector organ where the neurotransmitter is either adrenaline or noradrenaline.

The outflow of the parasympathetic nervous system is craniosacral. The cranial part originates from the midbrain and medulla (cranial nerves III, VII, IX and X) and the sacral outflow is from S2, S3 and S4. Their preganglionic neurones are usually long myelinated and synapse in ganglia close to the target organ and has Ach as its neurotransmitter. The unmyelinated postganglionic neurones is shorter and they synapse with effector organ. The neurotransmitter here is also Ach.

Both sympathetic and parasympathetic preganglionic neurons are cholinergic. Only the postganglionic parasympathetic neurons are cholinergic.

The superior mesenteric artery branches from the abdominal aorta just 1-2 cm below the origin of the celiac trunk. It lies posterior to the body of the pancreas and splenic vein and is separated from the aorta by the left renal vein. It passes forwards and inferiorly, anterior to the uncinate process of the pancreas and the third part of the duodenum, to enter the root of the small bowel mesentery and supply the midgut.

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

T10 – oesophageal opening in the diaphragm

T12 – Coeliac trunk, aortic hiatus in the diaphragm

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

The solid state of matter has a definite volume and shape and particles are packed closely together and are incompressible. Within this tight lattice, there is enough thermal energy to produce vibration of particles.

Liquids however have a volume but no definite shape. These particles are less tightly packed together. Although there is free movement within the volume, they are incompressible.

Gases, however, have no finite shape or volume and particles are free to move rapidly in a state of random motion. They are compressible and are completely shaped by the space in which they are held. Vapours exist as a gas phase in equilibrium with identical liquid or solid matter below its boiling point.

The most prevalent state of matter in the universe is plasma which is formed by heating atoms to very high temperatures to form ions.

There are four parathyroid glands that lie on the medial half of the posterior surface of each lobe of the thyroid gland, inside its sheath. There are two superior and two inferior parathyroid glands.

The common carotid artery is a lateral relation of the inferior parathyroid.

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

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

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

The inferior mesenteric artery originates 3-4 cm above the bifurcation of the abdominal aorta. The left colic artery branches off the inferior mesenteric artery, arising close to its origin from the abdominal aorta. Other branches of IMA include the three sigmoid arteries that supply the sigmoid colon.

The left colic artery branches off from IMA to supply the distal 1/3 of the transverse colon and the descending colon. It moves upwards posterior to the left colic mesentery and then travels anteriorly to the psoas major muscle, left ureter, and left internal spermatic vessels, before dividing into ascending and descending branches.

Sugammadex is used for immediate reversal of rocuronium-induced neuromuscular blockade.
It is used at a dose of 16 mg/kg.

Since the patient in the question is 70 kg, the required dose of sugammadex can be calculated as:
16×70 = 1120 mg.

Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action. Due to its 1:1 binding of rocuronium or vecuronium, it can reverse any depth of neuromuscular block.

The ECG changes seen in hypomagnesaemia include:

Prolonged PR interval
Prolonged QT interval
Flattening of T waves
ST segment depression
Prominent U waves

These changes are almost the same as those of hypokalaemia.

There is an increased risk of digoxin toxicity and a risk of atrial and ventricular ectopic and ventricular arrhythmias.

There is impaired synthesis and release of parathyroid hormone (PTH) in chronic hypomagnesaemia leading to impaired target organ response to PTH. This produces secondary hypocalcaemia.

The use of potassium ‘wasting’ diuretics (e.g. loop diuretics like furosemide) may lead to Hypomagnesaemia.

A tall T wave is seen in hypermagnesemia.

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

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

Dopamine (DA) is a dopaminergic (D1 and D2) as well as adrenergic ? and?1 (but not ?2 ) agonist.

The D1 receptors in renal and mesenteric blood vessels are the most sensitive: i.v. infusion of a low dose of DA dilates these vessels (by raising intracellular cAMP). This increases g.f.r. In addition, DA exerts a natriuretic effect by D1 receptors on proximal tubular cells.

Moderately high doses produce a positive inotropic (direct?1 and D1 action + that due to NA release), but the little chronotropic effect on the heart.

Vasoconstriction (?1 action) occurs only when large doses are infused.

At doses normally employed, it raises cardiac output and systolic BP with little effect on diastolic BP. It has practically no effect on nonvascular ? and ? receptors; does not penetrate the blood-brain barrier—no CNS effects.

Dopamine is used in patients with cardiogenic or septic shock and severe CHF wherein it increases BP and urine outflow.

It is administered by i.v. infusion (0.2–1 mg/min) which is regulated by monitoring BP and rate of urine formation

Mid-shaft fractures of the humerus usually occur after a direct blow to the upper arm, which can occur after a fall or RTAs.
The most important clinical significance of a mid-shaft humeral fracture is an injury to the radial nerve. The radial nerve originates from the brachial plexus and has roots of C5-T1. It crosses the spiral groove on the posterior side of the shaft of the humerus.
On examination, the patient may have a wrist drop, loss or weakness of finger extension, and decreased or absent sensation to the posterior forearm, digits 1 to 3, and the radial half of the fourth digit.

The humeral shaft has two compartments:
1. Anterior:
Brachial artery and vein
Biceps brachii, brachialis, coracobrachialis
Musculocutaneous, median, and ulnar nerves
2. Posterior:
Radial nerve
Triceps

Other significant nerve injuries are:
1. Axillary nerve – surgical neck fracture of the humerus
2. Brachial Artery – supracondylar fracture of the humerus
3. Axillary artery – surgical neck fracture of the humerus, but is relatively uncommon

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

SEM = SD / square root (n)

where SD = standard deviation and n = sample size

The operating theatre is an unusual place with several applications of electrical equipment to the human body. This can lead to potential dangers associated with it that need to be prevented. Electrical safety in the operation theatre is the understanding of how these potential dangers can occur and how they can be prevented.

Electricity can cause morbidity or mortality by one of the following ways:
(i) electrocution
(ii) burns
(iii) ignition of a flammable material, causing a fire or explosion.

Electrocution is dependant on factors like duration of contact with electric current, the current pathway and the frequency and size of current.

Option A: The higher the frequency, the less effects of electrocution on the body.

Option B & D: Equipment can be classified in classes and types.
The class designation describes the method used for protection against electrocution. Class I is basic protection, class II is double insulation and class III is safety extra low voltage.
The type designation describes the degree of protection based on the maximum permissible leakage currents under normal and fault conditions.
Type B:
can be class I, II or III but the maximum leakage current must not exceed 100 µA. It is therefore not suitable for direct connection to the heart.
Type BF
Similar to type B, but uses an isolated (or floating) circuit.
Type CF
Only type CF protect against microshock as they allow leakage currents of 0.05 mA per electrode for class I and 0.01 mA for class II. Microshock is a small leakage current that can cause harm because of direct connection to the heart via transvenous lines or wires, bypassing the impedance of the skin, leading to ventricular fibrillation. Microshock current of 100 ?A is sufficient to cause VF.

Option C: A 75mA electrocution can cause ventricular fibrillation. Use the following as a general guide to understand the effect of current size on the body.
1 mA – tingling pain
5 mA – pain
15 mA – tonic muscular contraction
50 mA – respiratory muscle paralysis
75 mA – ventricular fibrillation.

Option E: Wet skin reduces the resistance to current flow and therefore increases the effects of electrocution.

The neuromuscular blocking agent is likely to be filtered and not reabsorbed by the renal tubules due to an exclusion process.

Neuromuscular blocking agents that contain one or more quaternary nitrogen atoms are polar and ionised. As a result, the molecules have low lipid solubility, low membrane diffusion capacity, and low distribution volume.

It’s unlikely that a compound with three quaternary nitrogen atoms is an ester. Its high polarity would prevent molecules from moving quickly into tissues.

When drugs have a low hepatic extraction ratio (0.3), the venous and arterial drug concentrations are nearly identical. The liver is not the primary site of drug metabolism.

Therefore:

Changes in liver blood flow have no effect on clearance.
Protein binding, intrinsic metabolism, and excretion are all very sensitive to changes in clearance.
When taken orally, there is no first-pass metabolism.

There is no reason for the lungs to eliminate any neuromuscular blocking agent.

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

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

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

The oesophagus has four layers namely; 1. the mucosal layer, 2. the submucosal layer, 3. the muscular layer and 4. the layer of loose connective tissue which binds to the outer mucosal layer. The oesophagus lacks the serosal layer and therefore holds sutures poorly.

The mucosal layer consists of muscularis mucosa and the lamina propria and is made up of non keratinised stratified squamous epithelium. The mucosal layer is the innermost layer of the oesophagus.

The submucosal layer being the strongest layer of all has mucous glands which are called as the tuboalveolar mucous glands.

The outer muscular layer has two types of muscle layers of which one is the circular layer and the other the longitudinal layer. The Auerbach’s and Meissner’s nerve plexuses lie in between the longitudinal and circular muscle layers and submucosally. The muscle fibres present in the upper 1/3rd part of the oesophagus are skeletal muscle fibres, the middle 1/3rd layer has both smooth and skeletal muscle fibres, but the lower 1/3rd only has smooth muscle fibres.

The loose connective tissue layer or the adventitious layer has dense fibrous tissue.

There are 4 different types of globin chains which surround 4 heme molecules in haemoglobin (Hb) – α (alpha), β (beta), γ (gamma), and δ (delta)
α chains are essential.
δ2β2 and β2γ2 are not found in a healthy adult.
97% of the Hb in a healthy adult is made of α2β2 (2 α chains and 2 β chains).
α2δ2 accounts for around 1.5-3% of the adult Hb.
α2γ2 accounts for less than 1%.

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

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

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.

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

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

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

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

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

Her symptoms are suggestive of trigeminal neuralgia which is a short, sudden, severe sharp unilateral pain in the facial region. The pain often follows the sensory distribution of the trigeminal nerve (CN V).

The trigeminal nerve gives rise to 3 sensory and 1 motor nuclei. Neuralgia can arise from any of the 3 sensory divisions.

The ophthalmic division gives rise to 3 further sensory branches, which are the frontal, lacrimal and nasociliary.

The frontal branch of the ophthalmic division of the trigeminal nerve is responsible for the innervation of the area in question.

The superior alveolar dental, zygomatic and sphenopalatine nerves are all branches arising from the maxillary division of the trigeminal nerve.

The mandibular division of the trigeminal nerve provides sensory and motor innervation. The sensory innervation is carried out by the auriculotemporal nerve which supplies the lower third of the face, while the motor fibres are responsible for controlling the muscles of mastication.

The somatic sensory branches of the vagus nerve are responsible for sensory innervation of the external acoustic meatus and tympanic membrane.

The sacral hiatus is shaped by incomplete midline fusion of the posterior elements of the distal portion of S4 and S5. This inverted U shaped space is covered by the posterior aspect of the sacrococcygeal membrane and is an important landmark in caudal anaesthetic block. Distal most portion of the dural sac and the sacral hiatus usually terminate between levels S1 and S3. The dural sac ends at the level of S2 in adults and S3 in children.

An equilateral triangle is formed between the apex of the sacral hiatus and the posterior superior iliac spines. This triangle is used to determine the location of the sacral hiatus during caudal anaesthetic block.

Myasthenic and cholinergic crises are two crises which are similar in their clinical presentation.

Myasthenic crisis can be caused by:
-lack of acetylcholine,
-poor compliance with medication,
-infection

Cholinergic crisis can be caused by excess cholinesterase inhibitor medication (mimicking organophosphate poisoning) causing excess acetylcholine.

Differentiation between the 2 crises is made by giving incremental doses of the short acting cholinesterase inhibitor, Edrophonium.
This increase acetylcholine levels and will make a myasthenic crisis better and a cholinergic crisis worse.

Propranolol is a nonselective beta-blocker with a half-life of 3 to 6 hours.

Since it is lipid-soluble it crosses the blood-brain barrier and causes Central Nervous System side effects like sedation, nightmares, and depression.

They are contraindicated in asthma, Congestive heart failure, and diabetes.

It has a large volume of distribution with no intrinsic sympathomimetic action.

There are different effects of electrocution and these can be shown in the table below.

Current Effect
1 mA Tingling
5 mA Pain
15 mA Tonic muscle contraction
50 mA Respiratory arrest
100 mA Ventricular fibrillation and cardiac arrest

Selective ?1 -Blockers like prazosin, terazosin, doxazosin, and alfuzosin cause a decrease in blood pressure with lesser tachycardia than nonselective blockers (due to lack of ?2 blocking action.

The major adverse effect of these drugs is postural hypotension. It is seen with the first few doses or on-dose escalation (First dose effect).

Its half-life is approximately three hours.

It is excreted primarily through bile and faeces (not through kidneys)

This patient’s limited haematological profile includes mild normocytic anaemia and a normal platelet count.

Iron deficiency is the most common cause of anaemia during pregnancy. It affects 75 to 95 percent of patients. A haemoglobin level of less than 110 g/L in the first trimester and less than 105 g/L in the second and third trimesters is considered anaemia. There will usually be a low mean cell volume (MCV), mean cell haemoglobin (MCH), and mean cell haemoglobin concentration in addition to a low haemoglobin (MCHC). The MCV may be normal in mild cases of iron deficiency or coexisting vitamin B12 and folate deficiency.

To determine whether you have an iron deficiency, you’ll need to take more tests. Low serum ferritin (15 g/L) and less reliable indices like serum iron and total iron binding capacity are among them.

A number of factors contribute to iron deficiency in pregnancy, including:

Insufficient dietary iron to meet the mother’s and foetus’ nutritional needs
Multiple pregnancies
Blood loss, as well as
Absorption of iron from the gut is reduced.

The volume of plasma increases by about 50% during pregnancy, but the mass of red blood cells (RBCs) increases by only 30%. Dilutional anaemia is the result of this situation. From the first trimester to delivery, the RBC mass increases linearly, while the plasma volume plateaus, stabilises, or falls slightly near term. As a result, between 28 and 34 weeks of pregnancy, haemoglobin concentrations are at their lowest. The effects of haemodilution will be negated in this patient because she is 37 weeks pregnant.

Vitamin B12 and folate deficiency are less common causes of anaemia in pregnancy. The diagnosis could be ruled out if the MVC is normal.

During pregnancy, the platelet count drops, especially in the third trimester. Gestational thrombocytopenia is the medical term for this condition. It’s due to a combination of factors, including haemodilution and increased platelet activation and clearance. Pre-eclampsia and HELLP syndrome are common causes of thrombocytopenia. Pre-eclampsia isn’t the only cause of anaemia during pregnancy.

A typical blood picture of a haemoglobinopathy like sickle cell disease shows quantitative and qualitative defects, with the former leading to a severe anaemia exacerbated by haemodilution and other factors that contribute to iron deficiency. Microcytic cells are the most common type.

The principal innervation of the small muscles of the hand is T1.

9 & 27 can be obtained by subtracting and adding 9 from the mean. 9 is three times the standard deviation and we know that 99.7% values lie within 3 standard deviations from the mean. We can find the interval for 99.7% to verify in the following way:

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.

4. The range turns out to be 9-27 kg.

Organophosphate poisoning occurs most often due to accidental exposure to toxic amounts of pesticides. Signs and symptoms include diarrhoea, urination, miosis, bradycardia, emesis, lacrimation, lethargy and salivation.

Organophosphates are classified as indirect acting cholinomimetics, and their mode of action involves: (1) the inhibition of acetylcholinesterase (AChE) by forming a stable covalent bond on the active site serine; and, (2) amplification of endogenously release acetylcholine (ACh), hence the clinical manifestation.

There are 4 types of bonds or interactions: ionic, covalent, hydrogen bonds, and van der Waals interactions. Ionic and covalent bonds are strong interactions that require a larger energy input to break apart. When an element donates an electron from its outer shell, a positive ion is formed. The element accepting the electron is now negatively charged. Because positive and negative charges attract, these ions stay together and form an ionic bond. Covalent bonds form when an electron is shared between two elements and are the strongest and most common form of chemical bond in living organisms. Covalent bonds form between the elements that make up the biological molecules in our cells. Unlike ionic bonds, covalent bonds do not dissociate in water.

When polar covalent bonds containing a hydrogen atom form, the hydrogen atom in that bond has a slightly positive charge. This is because the shared electron is pulled more strongly toward the other element and away from the hydrogen nucleus. Because the hydrogen atom is slightly positive, it will be attracted to neighbouring negative partial charges. When this happens, a weak interaction occurs between the slightly positive charge of the hydrogen atom of one molecule and the slightly negative charge of the other molecule. This interaction is called a hydrogen bond.

Mapleson classified breathing systems into A, B, C, D and E. Jackson-Rees subsequently modified the Mapleson E by adding a double-ended bag to the end of the reservoir tubing, creating the Mapleson F. A Mapleson E or T-piece does not have a reservoir bag.

A Mapleson A system is a very efficient system for use during spontaneous ventilation. However, it is not suitable for use with patients less than 25 kg, due to the increased dead space at the distal / patient end. This system can be modified into a Lack system or coaxial Mapleson A, where the fresh gas flows through an outer tube (30 mm) and exhaled gases flow through the inner tube (14 mm).

The adjustable pressure limiting valve (APL) or expiratory valve allows exhaled gas and excess fresh gas to leave the breathing system. It is a one-way, adjustable spring-loaded valve, and gases escape when the pressure in the system exceeds the valve opening pressure. During spontaneous ventilation a pressure of less than 1 cm of water (0.1 kPa) is needed when the valve is in the open position (not 2 cm of H2O).

The reservoir bag is highly compliant and when over inflated, the rubber bag can limit the pressure in the system to about 40 cm of H2O.

This is due to the law of Laplace, which states that the pressure will fall as the radius of the bag increases:

Pressure = 2 x tension/radius.

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.

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 3 also assesses the efficacy but at a higher scale with larger population sample.

Phase 4 trials are involved with the long term effects and side effects of the drug.

In general practice, majority of phase 3 trials and some of the trials conducted in phase 2 are randomized. Because phase 4 trials require a huge sample size, they are not randomized as much. The primal reason behind conducting phase 3 trials is to test the efficiency and safety in a significant sample population. At this point it is assumed that the drug is effective up to a certain extent.

During a case-control study, subjects that exhibit outcomes of interest are compared with those who don’t show the expected outcome. The extent of exposure to a particular risk factor is then matched between cases and controls. If the exposure among cases surpasses controls, it becomes a risk factor for the outcome that is being studied.

Pilot studies are conducted on a lower and much smaller level, to assess if a randomized controlled trial of the crucial components of a study will be plausible.

Phase 4 trials are the ones that are conducted after its established that the drug is effective and is approved by the regulating authority for use. These trials are concerned with the side effects and potential risks associated with the long term usage of the drug.

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.

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

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

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

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

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

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

The potential difference (amplitude) and bandwidth frequencies of bioelectric signals are typical.

These are the following:

ECG: A bandwidth of 0.5-50 Hz is usually sufficient in monitoring mode, but a typical diagnostic bandwidth is 0.05-150 Hz (up to 200 Hz) with a typical voltage range of 0.1-4 millivolts (100-4000 microvolts).
EEG has a frequency range of 0.5-100 Hz and a voltage range of 0.5-100 microvolts.
EMG has a frequency range of 0.5 to 350 Hz and a voltage range of 0.5 to 30 millivolts.

Prior to display, these small signals will need to be amplified and processed further.

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

The femoral triangle is a wedge-shaped area found within the superomedial aspect of the anterior thigh. It is a passageway for structures to leave and enter the anterior thigh.

Superior: Inguinal ligament
Medial: Adductor longus
Lateral: Sartorius
Floor: Iliopsoas, adductor longus and pectineus

The contents include: (medial to lateral)
Femoral vein
Femoral artery-pulse palpated at the mid inguinal point
Femoral nerve
Deep and superficial inguinal lymph nodes
Lateral cutaneous nerve
Great saphenous vein
Femoral branch of the genitofemoral nerve

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

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

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

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

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

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

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

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

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 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).

Drug interactions can be seen in the following examples:

Additive interaction (summation).

Additive effects are described for intravenous drug combinations such as ketamine and thiopentone or ketamine and midazolam. Different mechanisms of action are used by them. Thiopentone and midazolam are GABAA receptor agonists, whereas ketamine is an NMDA receptor antagonist. Nitrous oxide and halothane are two other examples.

Synergism is a supra-additive interaction.

Refers to the administration of two drugs with similar pharmacological properties and closely related sites of action, resulting in a combined effect that is greater than the sum of the contributions of each component. The construction of an isobologram can be used to interpret and understand these. The best example is the hypnotic effect of benzodiazepines and intravenous induction agents like propofol. As part of a co-induction technique, midazolam is frequently given before propofol.

Potentiation

In a dose-dependent manner, volatile agents enhance the effects of neuromuscular blocking agents. Electrolyte disturbance (hypomagnesaemia), Penicillin, and probenecid can all increase the effects of neuromuscular blocking agents (the latter has no similar pharmacological activity).

Infra-additive interaction (antagonism).

This can be subdivided into the following categories:

-Pharmacokinetic interference occurs when one drug affects the absorption of another through the gastrointestinal tract or when hepatic microsomal enzyme induction influences metabolism.
-Heparin and protamine, for example, or heavy metals and chelating agents, are examples of chemical antagonists.
-Competitive reversible antagonistic antagonism of receptors, such as opioids and naloxone, and irreversible antagonistic antagonism of receptors

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.

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.

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%

The aminosteroid rocuronium is the neuromuscular blocking agent in question.

0.3 mg/kg is the effective dose 95 (ED95) (the dose required to depress the twitch height by 95 percent )
The dose for intubation is 0.6 mg/kg.
75 seconds is the time it takes to reach 95 percent depression of the first twitch of the train of four (ToF) or the onset time.
The clinical duration or time to 25% recovery of the first twitch of the train of four (ToF) is 33 minutes.

A modified cyclodextrin can quickly reverse both rocuronium and vecuronium (sugammadex).

It is more fat-soluble than vecuronium, with the liver absorbing the majority of the drug and excreting it in the bile. The only metabolite found in the blood (17-desacetylrocuronium) is 20 times less potent than the parent drug and is unlikely to cause neuromuscular block.

Despite its quick onset of action (60-90 seconds), suxamethonium arguably is still the neuromuscular blocker of choice for a quick sequence induction. Rocuronium is becoming increasingly popular for this purpose.

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.

Selection of a chest drain will depend on the external circumference.

A cannula, whether intravenous or intra-arterial, are classified according to standard wire gauge, which refers to the number of wires that can fit into the same hole. If a cannula is labelled 22G, then 22 wires will fit into the standard size hole.

A more popular measurement than SWG nowadays is cross sectional area.

When the concern for selecting equipment is the rate of flow, then it is important to consider the diameter and the radius of a parallel sided tube. These, however, are not routinely considered when comparing sizes of a cannula.

The right atrium receives blood supply from the SVC, IVC, and coronary sinus. It forms the right border of the heart.

The interior of the right atrium has 5 distinct features:
1. Sinus venarum – smooth, thin-walled posterior part of the right atrium where the SVC, IVC, and coronary sinus open
2. Musculi pectinati – an anterior rough, wall of pectinate muscles
3. Tricuspid valve orifice – the opening through which the right atrium empties blood into the right ventricle
4. Crista terminalis – separates the rough (musculi pectinati) from the smooth (sinus venarum) internally
5. Fossa ovalis – a thumbprint size depression in the interatrial septum which is a remnant of the oval foramen and its valve in the foetus

The trabeculae carneae are irregular muscular elevations that form the interior of the right ventricle.

Drug elimination is the termination of drug action, and may involve metabolism into inactive state and excretion out of the body. Duration of drug action is determined by the dose administered and the rate of elimination following the last dose.

There are two types of elimination: first-order and zero-order elimination.

In first-order elimination, the rate of elimination is proportionate to the concentration; the concentration decreases exponentially over time. It observes the characteristic half-life elimination, where the concentration decreases by 50% for every half-life.

In zero-order elimination, the rate of elimination is constant regardless of concentration; the concentration decreases linearly over time. A constant amount of the drug being excreted over time, and it occurs when drugs have saturated their elimination mechanisms.

Since phenytoin is observed in elevated levels, the elimination mechanisms for it has been saturated and, thus, will have to undergo zero-order elimination.

The hormone parathyroid hormone (PTH) and the receptor parathyroid hormone type 1 (PTH1-Rc) are important regulators of blood calcium homeostasis.

PTH can cause a rapid release of calcium from the matrix in bone, but it also affects long-term calcium metabolism by acting directly on bone-forming osteoblasts (by binding to PTH1-Rc) and indirectly on bone-resorbing osteoclasts.

PTH causes changes in the synthesis and/or activity of several proteins, including osteoclast-differentiating factor, also known as TRANCE or RANKL, when it acts on osteoblasts.

RANK receptors are found on the cell surfaces of osteoclast precursors. The osteoclasts are activated when RANKL binds to the RANK receptors. Osteoclasts lack PTH receptors, whereas osteoblasts do. Osteoclasts are activated indirectly when the RANK receptor binds to the RANKL secreted by osteoblasts, resulting in bone resorption. PTH1 receptors are found in osteoclasts, but they are few.

PTH activates G-protein coupled receptors in all target cells via adenylate cyclase.

The PTH2 receptor is most abundant in the nervous system and pancreas, but it is not a calcium metabolism regulator. It is abundant in the septum, midline thalamic nuclei, several hypothalamic nuclei, and the dorsal horn of the spinal cord, as well as the cerebral cortex and basal ganglia. Expression in pancreatic islet somatostatin cells is the most prominent on the periphery.

The distribution of the receptor is being used to test functional hypotheses. It may play a role in pain modulation and hypothalamic releasing-factor secretion control.

Doxycycline belongs to the family of tetracyclines and inhibits protein synthesis through reversible binding to bacterial 30s ribosomal subunits, which prevent binding of new incoming amino acids (aminoacyl-tRNA) and thus interfere with peptide growth.

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.

The STOP-BANG questionnaire is used to screen patients for obstructive sleep apnoea (OSA).

The scoring system assigns one point for each feature.

S: Snoring (louder than talking or loud enough to be heard through closed doors)
T: Feeling tired, fatigued, or sleepy during daytime
O: Observed apnoeas during sleep
P: Hypertension
B: BMI more than 35 kg/m2
A: Age 50-years of age or greater
N: Neck circumference (male 17 inches / 43cm or greater and female 16 inches / 41 or greater)
G: Gender: Male

Our patient has a score of 5 ( O, P, A, N, G)

The score helps clinicians stratify patients for unrecognized OSA and target appropriate clinical management. It can also help triage patients for further investigation. A STOP-BANG score of 5-8 will identify patients with high probability of moderate to severe OSA in the surgical population.

Static lung compliance refers to the change in volume within the lung per given change in unit pressure. It is usually measured when air flow is absent, such as during pauses in inhalation and exhalation.

It is a combination of:

Chest wall compliance: normal value is 200 mL/cmH2O
Lung tissue compliance: normal value is 200 mL/ cmH2O

It is represented mathematically as:

1/Crs = 1/Cl + 1/Ccw

Where,

Crs = total compliance of the respiratory system
Cl = compliance of the lung
Ccw = compliance of the chest wall

Therefore in this case:

1/Crs = 1/200 + 1/200

1/Crs = 0.005 + 0.005 = 0.01

1/Ct = 0.01

Rearranging equation gives:

Ct = 1/0.01 = 100 mL/cmH2O.

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

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

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

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

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

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

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

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

If there is no change in preload and myocardial contractility, there will be decrease in end-diastolic volume and stroke volume. So there must be increase in end-systolic volume.

The surface marking for locating the femoral artery is the mid-inguinal point, which is the halfway point between the anterior superior iliac spine (ASIS) and the pubic symphysis.

The other mentioned options are not specific for any landmark.

However, it is important to note the difference between the mid inguinal point and the midpoint of the inguinal ligament, which is travels from the ASIS to the pubic tubercle.

Dopamine (DA) is a dopaminergic (D1 and D2) as well as adrenergic ? and?1 (but not ?2 ) agonist.

The D1 receptors in renal and mesenteric blood vessels are the most sensitive: i.v. infusion of a low dose of DA dilates these vessels (by raising intracellular cAMP). This increases g.f.r. In addition, DA exerts a natriuretic effect by D1 receptors on proximal tubular cells.

Moderately high doses produce a positive inotropic (direct?1 and D1 action + that due to NA release), but the little chronotropic effect on the heart.

Vasoconstriction (?1 action) occurs only when large doses are infused.

At doses normally employed, it raises cardiac output and systolic BP with little effect on diastolic BP. It has practically no effect on nonvascular ? and ? receptors; does not penetrate the blood-brain barrier—no CNS effects.

Dopamine is used in patients with cardiogenic or septic shock and severe CHF wherein it increases BP and urine outflow.

It is administered by i.v. infusion (0.2–1 mg/min) which is regulated by monitoring BP and rate of urine formation

Bupivacaine is used to decrease sensation in a specific area. It is injected around a nerve that supplies the area, or into the spinal canal’s epidural space.

The maximum volume of 0.5% bupivacaine that should be administered to a 10kg child is 5 ml

Absolute risk reduction = (Control event rate) – (Experimental event rate)

Experimental event rate = 24 / 120 = 0.2

Control event rate = 60 / 240 = 0.25

Absolute risk reduction = 0.25 – 0.2 = 0.05 = 5% reduction

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

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

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

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

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

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

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

Codeine is easily absorbed from the gastrointestinal tract and converted to morphine and norcodeine in the liver via O- and N-demethylation. Morphine and norcodeine are excreted almost entirely by the kidney, primarily as conjugates with glucuronic acid.

By glucuronidation, phase II metabolism enzyme UDP-glucuronosyl transferase-2B7 converts morphine to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) (UGT2B7).

Approximately 60% of morphine is converted to M3G, with the remaining 6-10% converted to M6G. M3G is inactive, but M6G is said to be 4 to 650 times more potent on the MOP receptor than morphine.

When codeine is consumed, cytochrome P450 2D6 in the liver converts it to morphine (CYP2D6).

Some people have DNA variations that increase the activity of this enzyme, causing codeine to be converted to morphine more quickly and completely than in others. After taking codeine, these ultra-rapid metabolisers are more likely to have higher than normal levels of morphine in their blood.

Respiratory depression/obstruction can be caused by high levels of morphine and M6G, especially in people who have a history of obstructive sleep apnoea. The estimated number of ultra-rapid metabolisers ranges from 1 to 7 per 100 people, but some ethnic groups may have as many as 28 per 100 people.

The mechanism of action of macrolides is inhibition of bacterial protein synthesis by preventing peptidyltransferase from adding to the growing peptide which is attached to tRNA to the next amino acid.

The external urethral sphincter functions to provide voluntary control of urine flow from the bladder to the urethra.

It receives its innervation from the branches of the pudendal nerve which originate from S2, S3 and S4.

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.

The equation for calculating vaporiser output is:

Vaporiser output (VO) mL = Carrier gas flow (mL/minute) × SVP of agent (kPa)
Ambient pressure (kPa) − SVP of agent (kPa)

The saturated vapour pressure of sevoflurane at 1 atm (100 kPa) and 20°C is 21 kPa.

VO = (100 mL × 21 kPa)/(100 kPa − 21kPa) for sevoflurane,
VO = 26.6 mL

26.6 mL of 100% sevoflurane and 100 mL bypass carrier gas is being added to the fresh gas flow per minute.

2660 mL of 1% sevoflurane and 100 mL bypass carrier gas is approximately 2.7 L/minute.

Certain skeletal muscles are more resistant to the effects of neuromuscular blocking agents, both non-depolarizing and depolarizing. The diaphragm is the most resistant. The muscles of the larynx and the corrugator supercilii are less resistant. The abdominal, orbicularis oris, and limb peripheral muscles are the most sensitive muscles.

Twitch stimulation patterns:

Supramaximal single stimulus:

The frequency ranges from 1 Hz to 0.1 Hz (one every second to one every 10 seconds)
The response is proportional to the frequency of the event.
It has limited clinical utility because it only tells you whether or not a patient is paralysed (no information on degree of paralysis).

Over the course of 0.5 seconds (2 Hz), four supramaximal stimulate were applied:

It is possible to see ‘fade’ and use it as a basis for evaluation.
This stimulation pattern is used to determine the degree of blockade (1-2 twitches is appropriate for abdominal surgery)
If the train of four (TOF) count is 1-2, reversal agents can be used in conjunction with medium-acting neuromuscular blocking agents.

Ratio of TOF:

This is the ratio of the 4th twitch amplitude to the 1st twitch amplitude.
The ratio decreases with non-depolarising block and is inversely proportional to the degree of block, allowing objective measurement of residual neuromuscular blockade.
To achieve adequate reversal, the ratio (as measured by accelerography) must be between 0.7 and 0.9.

Count of twitches after a tetanic experience(PTC):

50 Hz for 5 seconds, then a 3 second pause, followed by a single 1 Hz twitch stimulus.
When the TOF count is zero, this stimulation pattern is used to assess deep blockade (that is, in neurosurgery, microsurgery or ophthalmic surgery when even small movements of a patient will disturb the surgical field)
It gives an estimate of how long it will take for the response to return to single twitches, allowing assessment of blocks that are too deep for any other technique.
A palpable post-tetanic count (PTC) of 2 indicates no twitch response for about 20-30 minutes, and a PTC of 5 indicates no twitch response for about 10-15 minutes.

This is without a doubt the best way to keep track of paralysis in patients who need to avoid diaphragmatic movement. It’s best to use drug infusions and aim for a PTC of 2. After a tetanic stimulus, acetylcholine is mobilised, causing post-tetanic potentiation.

Stimulation in Two Bursts:

750 milliseconds between two short bursts of 50 Hz
This stimulation pattern is used to assess small amounts of residual blockade manually (tactile).

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

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

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

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

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

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

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

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

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

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

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

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

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

ID = Cpss × CL

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

ID = Cpss × 20

Therefore,

Cpss = 100 mg/20000 ml

Cpss = 0.005 mg/mL or 5 mcg/mL

The incidence of a disease is the number of new cases of the disease in a population over a defined time period.

The prevalence of a disease is the number of cases of the disease in a population over a defined time period describes. It is NOT the number of new cases.

The number of new cases of a disease only, has no denominator (time period or population) from which to derive an incidence.

The number of new cases of a disease seeking medical treatment is the incidence of patients seeking medical treatment NOT the incidence of the disease in a population.

The death rate from a disease is the number of patients dying from the disease in a population.

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

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

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

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

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

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

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

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

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

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

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

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

In first order kinetics the rate of elimination is proportional to plasma concentration.

Rate of elimination is described by the following equation:

C = C0. e^-kt

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

The initial concentration of this drug is 12 mcg/ml therefore:

The plasma concentration will have halved to 6 mcg/ml at 2 hours.
The plasma concentration will have halved to 3 mcg/ml at 4 hours and
The plasma concentration will have halved to 1.5 mcg/ml t 6 hours.

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.

Ondansetron is a serotonin antagonist at the 5HT3 receptor. 5HT3 receptors in the gastrointestinal tract and in the vomiting centre of the medulla participate in the vomiting reflex. They are particularly important in vomiting caused by chemical triggers such as cancer chemotherapy drugs.

The nucleus solitarius is the recipient of all visceral afferents, and an essential part of the regulatory centres of the internal homeostasis, through its multiple projections with cardiorespiratory and gastrointestinal regulatory centres. It participates in the reflexes of the nerves innervating the nucleus, so it mediates cough reflex, carotid sinus reflex, gag reflex, and vomiting reflex.

The ileocolic artery is the terminal branch of the superior mesenteric artery. It supplies:
1. terminal ileum
2. proximal right colon
3. cecum
4. appendix (via its branch of the appendicular artery)

As veins accompany arteries in the mesentery and are lined by lymphatics, high ligation is the norm in cancer resections—the ileocolic artery branches off the SMA near the duodenum.

This clinical trial consists over 1000 patients being evaluated for the response to a new treatment against a currently licensed treatment for ulcerative colitis. Therefore, it is comparing its efficacy to an established therapeutic or control in a larger population of volunteers. These are the characteristics of a phase III clinical trial.

The guidelines for the management of cardiac arrest in hypothermic patients published by the UK Resuscitation Council differ slightly from the standard algorithm.

In a patient with a core temperature of less than 30°C, do the following:

If you’re on the shockable side of the algorithm (VF/VT), you should give three DC shocks.
Further shocks are not recommended until the patient has been rewarmed to a temperature of more than 30°C because the rhythm is refractory and unlikely to change.
There should be no drugs given because they will be ineffective.

In a patient with a core temperature of 30°C to 35°C, do the following:

DC shocks are used as usual.
Because they are metabolised much more slowly, the time between drug doses should be doubled.

Active rewarming and protection against hyperthermia should be given to the patient.

Option e is false because there is insufficient information to determine whether resuscitation should be stopped.

Opioid should be avoided in the caesarean section as it crosses the placental membrane and causes respiratory depression.

Even though inhalational and intravenous anaesthetic agents readily cross the placenta, they do not have significant effects on APGAR score when used in clinical doses.

Vecuronium and suxamethonium are highly polar molecules and thus do not cross the placenta in significant amounts.