The rima glottidis is a narrow, triangle-shaped opening between the true vocal cords.

The vocal folds (true vocal cords) control sound production. The apex of each fold projects medially into the laryngeal cavity.

Each vocal fold includes these vocal ligaments:

Vocalis muscle (most medial part of thyroarytenoid muscle)

The glottis is composed of the vocal folds, processes and rima glottidis.

The rima glottidis is the narrowest potential site within the larynx, as the vocal cords may be completely opposed, forming a complete barrier.

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

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

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

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

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

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

Secreted T4 and T3 circulate in the bloodstream almost entirely bound to proteins. Normally only about 0.03% of total plasma T4 and 0.3% of total plasma T3 exist in the free state. Free T3 is biologically active and mediates the effects of thyroid hormone on peripheral tissues in addition to exerting negative feedback on the pituitary and hypothalamus. The major binding protein is thyroxine-binding globulin (TBG), which is synthesized in the liver and binds one molecule of T4 or T3. About 70% of circulating T4 and T3 is bound to TBGl 10% to 15% is bound to another specific thyroid-binding protein called transthyretin (TTR). Albumin binds 15% to 20%, and 3% to lipoproteins. Ordinarily only alterations in TBG concentration significantly affect total plasma T4 and T3 levels.

Two important biological functions have been ascribed to TBG. First, it maintains a large circulating reservoir of T4 that buffers any acute changes in thyroid gland function. Second, binding of plasma T4 and T3 to proteins prevents loss of these relatively small hormone molecules in urine and thereby helps conserve iodide. TTR transports T4 in CSF and provides thyroid hormones to the CNS.

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

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

Opioid receptors are a large family of seven transmembrane domain receptors. They are of four types:

1) Delta opioid receptor

2) Mu opioid receptor

3) Kappa opioid receptor

4) Orphan receptor-like 1

They contain about 372-400 amino acids and thus their molecular weight is different.

Opioid receptor activation reduces the intracellular cAMP formation and opens K+ channels (mainly through µ and δ receptors) or suppresses voltage-gated N-type Ca2+ channels (mainly κ receptor). These actions result in neuronal hyperpolarization and reduced availability of intracellular Ca2+ which results in decreased neurotransmitter release by cerebral, spinal, and myenteric neurons (e.g. glutamate from primary nociceptive afferents).

However, other mechanisms and second messengers may also be involved, particularly in the long-term

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.

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

So,

ARR= (10/400)-(20/400)

ARR= 0.025-0.05

ARR= 0.025 (Numerical Value)

Salmeterol is a long-acting Beta 2 selective agonist. Therefore it is only used for prophylaxis whereas salbutamol is a short-acting Beta 2 agonist and is thus used for the treatment of acute attacks of asthma.

Salmeterol is 15 times more potent than salbutamol at the Beta 2 receptor but 4 times less potent at the Beta 1 receptor.

Tachyphylaxis to the unwanted side effects commonly occurs, but not to bronchodilation.

This may be the classical case of blood transfusion reaction due to ABO incompatibility.

Here red cells are destroyed in the bloodstream with the release of haemoglobin in circulation (causing haemoglobinuria). Here, IgM or IgG anti-A or anti-B antibody can cause rapid activation of complement cascade usually the classical pathway. This is called intravascular haemolysis.

There may be extravascular haemolysis by cells of the mononuclear phagocyte system situated in the liver and spleen. Extravascular red cell destruction can increase breakdown products of haemoglobin, such as bilirubin and urobilinogen.

The measurements of GFR are done using renally inert indicators like inulin, where passive rate of filtration at the glomerulus = rate of excretion. Normal value is about 180 litres per day.

GFR is altered by renal blood flow but blood flow does not need to be measured.

The reabsorption of Na leads to a low excretion rate and low urine concentration and therefore its use as an indicator would lead to an erroneously LOW GFR.

If there is tubular secretion of any solute, the clearance value will be higher than that of inulin. This will be either due to tubular reabsorption or the solute not being freely filtered at the glomerulus.

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

T12 – Coeliac trunk

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

The thyroid gland is a gland shaped like a butterfly which lies at the base of the anterior neck. It controls metabolism using hormone secretion.

Iodine is extremely important for the synthesis of hormones within the thyroid. It is internalised into the thyroid follicular cells via the sodium/iodide symporter (NIS).

The parathyroid glands are found posterior to the thyroid gland, with the recurrent laryngeal nerves running posteromedially.

The expected weight of a normal thyroid gland is about 30 grams.

The left subclavian artery originates from the aortic arch, while the right subclavian artery originates from the brachiocephalic artery.

The subclavian artery gives off branches on both sides of the body:
1. Vertebral artery
2. Internal thoracic artery
3. Thyrocervical trunk
4. Costocervical trunk
5. Dorsal scapular artery

The superior thyroid artery is the first branch of the external carotid artery. The other branches of the external carotid artery are:
1. Superior thyroid artery
2. Ascending pharyngeal artery
3. Lingual artery
4. Facial artery
5. Occipital artery
6. Posterior auricular artery
7. Maxillary artery
8. Superficial temporal artery

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.

Lesser the potency of the drug, the higher the dose required to produce maximal receptor occupation. So, the least potent drug will have a log dose-response curve furthest to the right on X-axis.

Based on the option given, tramadol is the least potent drug and thus higher dose is required to produce maximal opioid receptor occupation.

Thus, Tramadol is the least potent opioid with a log dose-response curve furthest to the right on X-axis.

Note, Fentanyl is the most potent opioid with a log dose-response curve furthest to the left on the X-axis.

To denote large measured units, the following SI mathematical prefixes are used:

1 deca = 10 bytes (101)
1 hecto (h) = 100 bytes
1 kilo (k)= 1,000 bytes
1 mega (M) = 1,000,000 bytes
1 giga (G) = 1,000,000,000 bytes
1 Tera (T) = 1,000,000,000,000 bytes
1 Peta (P) = 1,000,000,000,000,000 bytes

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 sternocleidomastoid muscle divides the neck into anterior and posterior triangles on both sides of the neck.

The posterior triangle has the following boundaries:
anteriorly – sternocleidomastoid muscle
posteriorly – trapezius
roof – investing layer of deep cervical fascia
floor – prevertebral fascia overlying splenius capitis, levator scapulae, and the scalene muscles

The contents of the posterior triangle are:
1. fat
2. lymph nodes (level V)
3. accessory nerve
4. cutaneous branches of the cervical plexus – greater auricular nerve, transverse cervical nerve, lesser occipital nerve, supraclavicular nerve (A major branch of this plexus is the phrenic nerve, which arises from the anterior divisions of spinal nerves C3-C5)
5. inferior belly of omohyoid
6. branches of the thyrocervical trunk (transverse cervical and suprascapular arteries)
7. third part of the subclavian artery
8. external jugular vein

Taste sensation from the anterior two-thirds of the tongue is carried by chorda tympani, a branch of the facial nerve.

The general somatic sensation of the anterior two-third of the tongue is supplied by the lingual nerve, a branch of the mandibular nerve.

Both general somatic sensation and taste from the posterior third of the tongue are carried by the glossopharyngeal nerve.

All the muscles of the tongue except palatoglossus are supplied by the hypoglossal nerve whereas palatoglossus is supplied by the vagus nerve. (This is because palatoglossus is the only tongue muscle derived from the fourth branchial arch)

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

For establishing a cause effect relationship, following criteria must be met:

1. Coherence & Consistency

2. Temporal Precedence

3. Specificity

As can be seen, sensitivity (The probability of a positive test) is not among these deciding factors..

Hypochondriasis is an illness anxiety disorder, and describes excessively worriedness about the presence of a disease. While the woman is concerned about her possibility of developing motor neurone disease, she understands that no symptoms have yet appeared. Hypochondriasis involves patients who refuse to accept that they don’t have the disease, even if the results come back negative.

Late Look Bias occurs when the data is gathered or analysed at an inappropriate time e.g. when many of the subjects suffering from a fatal disease have died. This type of biasness might occur in some retrospective studies of motor neurone disease, but is not applicable to this prospective study.

In procedure bias, the researcher decides assignment of a treatment versus control and assigns particular patients to one group or the other non-randomly. This is unlikely to have occurred in this case, although it is not mentioned specifically. Of all the options, lead time-bias is a better answer.

The Hawthorne Effect refers to groups modifying their behaviour simply because they are aware of being observed. Any differences in the behaviour have not been mentioned in the question, and it is highly unlikely that a change in patient’s behaviour would have affected their length of survival in this case.

The correct option is lead-time bias. Even if the new blood test diagnoses the disease earlier, it doesn’t affect the outcome, as the survival time was still on average 43 months from the onset of symptoms in both groups. With the help of blood test, the disease was only detected 8 months earlier.

Breathing system is an assembly of components which connects patient’s airway to anaesthesia machine through which controlled composition of gas mixture is dispensed. It delivers gas to the patient, removes expired gas and controls the temperature and humidity of the inspired mixture. It allows spontaneous, controlled, or assisted respiration. It may also provide ports for gas sampling, airway pressure, flow and volume monitoring.

Breathing systems have been classified by Conway and Mapleson.
Conway suggested a functional classification:
– Circuits requiring a CO2 absorber
– Circuits not requiring a CO2 absorber

William Mapleson designated varying arrangements of breathing system components (masks, breathing tubes, fresh gas flow inlets, adjustable pressure-limiting valves, and reservoir bags) as Mapleson A-E circuits.
Mapleson A: Arranged as FGF inlet, reservoir bag, APL valve, mask.
In this circuit, because the reservoir bag is between the FGF inlet valve and the APL valve, expired gas from the patient may re-enter the system and fill the reservoir bag during controlled ventilation. This is the most efficient system for spontaneous breathing as the FGF must only be equal to a patient’s minute ventilation to prevent rebreathing.

Mapleson B: Arranged as reservoir bag, FGF inlet, APL valve, mask.
In this circuit, the FGF inlet is closer to the APL valve, which helps prevent the rebreathing concern in the Mapleson A circuit as above during controlled ventilation.

Mapleson C: Arranged as reservoir bag, FGF inlet, APL valve, mask.
In this circuit, the arrangement is the same as the Mapleson B circuit. However, this circuit is shorter as it does not contain elongated corrugated tubing. This circuit also has the FGF inlet close to the APL valve to aid in preventing rebreathing.

Mapleson D: Arranged as reservoir bag, APL valve, FGF inlet, and mask.
In this circuit, the arrangement interchanges the FGF inlet and APL valve of the Mapleson A circuit. This system prevents rebreathing by directing FGF towards the APL valve rather than towards the patient during exhalation.

Mapleson E: Arranged as corrugated tubing, FGF inlet, and mask.
In this circuit, there is no reservoir bag and no APL valve. Given the inability to alter the pressure of the circuit, this is ideal for spontaneously ventilating neonates or paediatric patients where low-pressure ventilation is desired. The system prevents rebreathing, similar to the Mapleson D circuit.

Jackson Rees later modified the Mapleson E by adding an open ended bag, which has since become known as the Mapleson F.
Mapleson F: Arranged as APL valve directly connected to reservoir bag, corrugated tubing, FGF inlet, and mask.
The system prevents rebreathing similarly to Mapleson D by directing FGF towards the APL valve.

The ‘ideal’ alveolar PO2 minus arterial PO2 is the alveolar-arterial (A-a) oxygen difference.

The ‘ideal’ alveolar PO2 is derived from the alveolar air equation and is the PO2 that the lung would have if there was no ventilation-perfusion (V/Q) inequality and it was exchanging gas at the same respiratory exchange ratio as real lung.

The amount of oxygen in the blood is measured directly in the arteries.

The A-a oxygen difference (or gradient) is a useful measure of shunt and V/Q mismatch, and it is less than 2 kPa in normal adults breathing air (15 mmHg). Because the shunt component is not corrected, the A-a difference increases when breathing 100 percent oxygen, and it can be up to 15 kPa (115 mmHg).

An abnormally low or abnormally high V/Q ratio within the lung can cause an increased A-a difference, though the former is more common. Atelectasis, which results in a low V/Q ratio, is the most likely cause of an A-a difference in a healthy adult breathing 100 percent oxygen.

Hypoventilation may cause an increase in alveolar (and thus arterial) CO2, lowering alveolar PO2 according to the alveolar air equation.

The alveolar PO2 is also reduced at high altitude.

Healthy people are unlikely to have a right-to-left shunt or an oxygen transport diffusion defect.

Gentamicin is a broad-spectrum antibiotic whose mechanism of action involves inhibition of protein synthesis by binding to 30s ribosomes. Its major adverse effect is nephrotoxicity and ototoxicity

Aminoglycoside bind to 30s subunit of ribosome causing misreading of mRNA

Tetracyclines inhibit protein synthesis through reversible binding to bacterial 30s ribosomal subunits, which prevent binding of new incoming amino acids (aminoacyl-tRNA) and thus interfere with peptide growth.

Chloramphenicol binds to the 50s subunit and inhibits peptidyl transferase

Clindamycin binds to the 50s ribosomal subunit of bacteria and disrupts protein synthesis by interfering with the transpeptidation reaction, which thereby inhibits early chain elongation.

The ASA physical status classification system is a system for assessing the fitness of patients before surgery. It was last updated in October 2014.

ASA I A normal healthy patient
ASA II A patient with mild systemic disease
ASA III A patient with severe systemic disease
ASA IV A patient with severe systemic disease that is a constant threat to life
ASA V A moribund patient who is not expected to survive without the operation
ASA VI A declared brain-dead patient whose organs are being removed for donor purposes

A 20-year old woman who is 39-weeks pregnant with no other medical conditions – ASA II

A 35-year-old man with a BMI of 29 with a good exercise tolerance who smokes-ASA II

A 50-year old man with a BMI of 41 with a reduced exercise tolerance -ASA III

A 65-year old woman with a BMI of 34 with treated hypertension with no functional limitations-ASA II

A 73-year old man who has had a TIA ten-weeks ago but has a good exercise tolerance and is a non-smoker-ASA IV

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

Oxytocin acts through G protein-coupled receptor and phosphoinositide-calcium second messenger system to contract uterine smooth muscle.

It has 0.5 to 1 % ADH activity introducing possibilities of water intoxication when used in high doses.

The sensitivity of the uterus to oxytocin increases as the pregnancy progresses.

It is used for induction of labour in post maturity and uterine inertia.

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

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

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

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

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

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

Albumin synthesis begins to increase after 48 hours.

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

The total body water content of a 70kg man is (70 × 0.6) = 42 litres. For a woman, the calculation is (70 × 0.55) = 38.5 litres.

For a man, it is subdivided into:

Extracellular fluid (ECF) = 14L (1/3)
Intracellular fluid (ICF) = 28L (2/3).

The ECF volume is further divided into:

Interstitial fluid = 10.5 litres
Plasma = 3 litres
Transcellular fluid (CSF/synovial fluid) = 0.5 litres.

Directly measured fluid compartments:

Heavy water (deuterium) can be used to measure total body water content, which is freely distributed.
Albumin labelled with a radioactive isotope or using a dye called Evans blue can be used to measure Plasma volume . They do not diffuse into red blood cells.
Radiolabelled (Cr-51) red blood cells can be used to measure total erythrocyte volume.
Inulin as the tracer can be used to measure ECF volume as it circulate freely in the interstitial and plasma volumes.

Indirectly measured fluid compartments:

Total blood volume can be calculated with the level of haematocrit and the volume of total circulating red blood cells.
ICF volume can be calculated by subtracting ECF volume from total blood volume.