Changes in the osmolality of body fluids (changes as minor as 1% are sufficient) play the most important role in regulating AVP secretion. The receptors that monitor changes in osmolality of body fluids (termed osmoreceptors) are distinct from the cells that synthesize and secrete AVP, and are located in the organum vasculosum of the lamina terminalis (OVLT) of the hypothalamus. The osmoreceptors sense changes in body osmolality by either shrinking or swelling. When the effective osmolality of the plasma increases, the osmoreceptors send signals to the AVP synthesizing/secreting cells located in the supraoptic and paraventricular nuclei of the hypothalamus, and AVP synthesis and secretion are stimulated. Conversely, when the effective osmolality of the plasma is reduced, secretion is inhibited. Because AVP is rapidly degraded in the plasma, circulating levels can be reduced to zero within minutes after secretion is inhibited.

In this scenario, the osmolality of the plasma will decrease to an estimate of 2.5%, hence inhibition of AVP.

Stimulation of atrial stretch receptors is incorrect because the increase in plasma volume is still below the threshold for its activation.

Osmotic diuresis is incorrect because 5% dextrose is isotonic, hence osmotic diuresis is not probable.

Renin is inhibited when an excess of NaCl in the tubular fluid is sensed by the macula densa.

The coronary sinus is large venous structure located on the posterior aspect of the left atrium, coursing within the left atrioventricular groove. The function of the coronary sinus is to drain the venous blood from the majority of the heart. It opens into the right atrium between the opening of inferior vena cava, the fossa ovalis and the right atrioventricular orifice. The coronary sinus is often guarded by a thin, semicircular endocardial fold, also known as the thebesian valve.
Tributaries include: Great cardiac vein, middle cardiac vein, small cardiac vein, posterior vein of left ventricle, oblique vein of left atrium. The great cardiac vein is the largest tributary of the coronary sinus.

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

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

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

Ketamine is the substance in question. Its structure and pharmacodynamic effects make it a one-of-a-kind intravenous induction agent. The molecule is made up of two cyclohexanone rings (2-(O-chlorophenyl)-2-methylamino cyclohexanone and 2-(O-chlorophenyl)-2-methylamino cyclohexanone). Ketamine has local anaesthetic properties and acts primarily on the brain and spinal cord.

It affects Ca2+ channels as a non-competitive antagonist for the N-D-methyl-aspartate (NMDA) receptor. It also acts as a local anaesthetic by interfering with neuronal Na+ channels.

Ketamine causes profound dissociative anaesthesia (profound amnesia and analgesia) as well as sedation.

Phenoxybenzamine, an alpha-1 adrenoreceptor antagonist, is an example of an irreversible competitive antagonist. It forms a covalent bond with the calcium influx receptor.

Benzodiazepines are GABAA receptor agonists that affect chloride influx.

Flumazenil is an inverse agonist that affects GABAA receptor chloride influx.

Ketamine is a cyclohexanone derivative that acts as a non-competitive Ca2+ channel antagonist.

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).

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.

Refractometers measure the degree to which the light changes direction, called the angle of refraction. A refractometer takes the refraction angles and correlates them to refractive index (nD) values that have been established. Using these values, you can determine the concentrations of solutions.

The external carotid artery has eight important branches:
Anterior surface:
1. Superior thyroid artery (first branch)
2. Lingual artery
3. Facial artery
Medial branch
4. Ascending pharyngeal artery
Posterior branches
5. Occipital artery
6. Posterior auricular artery
Terminal branches
7. Maxillary artery
8. Superficial temporal artery

The external carotid has eight branches, 3 from its anterior surface ; thyroid, lingual and facial. The pharyngeal artery is a medial branch. The posterior auricular and occipital are posterior branches.

Warming, humidifying, and filtering inspired anaesthetic gases is done by heat and moisture exchangers (HME) and breathing system filters. They are made of glass fibres materials and are supported by a sturdy frame. Pleating increases the surface area to reduce resistance to air flow and boost efficiency.

Filters’ effectiveness is determined by the amount and size of particles they keep out of the patient’s airway. The efficiency of filters might be classified as 95, 99.95, or 99.97 percent. Pores with a diameter of 0.2 µm are common. The following are examples of typical particle sizes:
Red blood cell – 5 µm
Lymphocyte – 5-8 µm
Viruses – 0.02-0.3 µm
Bacteria – 0.5-1 µm
Depending on particle size, gas flow speed, and charge, particles are collected via a number of processes. Mechanical sieve, interception, diffusion, electrostatic filtration, and inertial impaction are some of the options:

Sieve:
The diameter of the particle the filter is supposed to collect is smaller than the apertures of the filter’s fibres.

Interception:
When a particle following a gas streamline approaches a fibre within one radius of itself, it becomes attached and captured.
Diffusion:

A particle’s random (Brownian) zig-zag path or motion causes it to collide with a fibre.
By attracting and capturing a particle from within the gas flow, it generates a lower-concentration patch within the gas flow into which another particle diffuses, only to be captured. At low gas velocities and with smaller particles (0.1µm diameter), this is more common.

Electrostatic:

These filters use large diameter fibre media and rely on electrostatic charges to improve fine particle removal effectiveness.

Impaction due to inertia:

When a particle is too large to respond fast to abrupt changes in streamline direction near a filter fibre, this happens. Because of its inertia, the particle will continue on its original course and collide with the filter fibre. When high gas velocities and dense fibre packing of the filter media are present, this sort of filtration mechanism is most prevalent.

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.

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.

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.

Cardiopulmonary exercise testing (CPX, CPEX, CPET) is a non-invasive testing method used to determine the performance of the heart, lungs and skeletal muscle. It measures the exercise tolerance of the patient.

The parameters measured include:

ECG and ST-segment analysis and blood pressure
Oxygen consumption (VO2)
Carbon dioxide production (VCO2)
Gas flows and volumes
Respiratory exchange ratio (RER)
Respiratory rate
Anaerobic threshold (AT)

The anaerobic threshold (AT) is an estimate of exercise ability. Any measurement below 11 ml/kg/min is usually related with an increase in mortality, especially when there is a background of myocardial ischaemia occurring during the test.

Peak VO2 <20 mL/kg with a low AT have a correlation with postoperative complications and a 30 day mortality. The CPX test is used for risk-testing patients prior to surgery to determine the appropriate postoperative care facilities.

The V slope measured in CPX testing represents VO2 versus VCO2 relationship.

During AT, the ramp of V slope increases, but does not provide a picture of postoperative mortality.

The ideal gas equation makes the following assumptions:

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

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

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

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

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

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

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

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

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

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.

Number needed to treat (NNT) is a time specific epidemiological measure that indicates how many patients would be require for an intervention to prevent one additional bad outcome. A perfect NNT would be 1, where everyone improves with treatment, thus the higher the NNT, the less effective the treatment.

Thus if you treat 1000 patients then you will expect to have 50 fewer strokes.

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.

Because enflurane is much less soluble in blood and has a blood: gas partition coefficient of 1.8, both wash-in and wash-out should be faster.

Sevoflurane’s sweet-smelling, non-irritant nature, combined with a low blood: gas partition coefficient, would result in similar offset and onset characteristics.

Isoflurane and enflurane have a molecular weight of 184.

The oil: gas partition coefficient on a volatile agent is a measure of lipid solubility, potency, and thus MAC. Halothane has an oil: gas partition coefficient of 220 and a MAC of 0.74. One would expect the MAC to be higher with an oil gas partition coefficient of 180 (less lipid soluble).

The conversion of halothane (20%) to trifluoroacetic acid via oxidative metabolism has been linked to the development of hepatitis.

P450 2E1 converts sevoflurane to hexafluoroisopropanol, which results in the release of inorganic fluoride ions. It’s the only fluorinated volatile anaesthetic that doesn’t break down into trifluoracetic acid.

Desflurane is likely to cause airway irritation, which can lead to coughing, apnoea, and laryngospasm, despite its low blood:gas partition coefficient (0.42).

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

The following are symptoms of moderate asthma:

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

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

Airway obstruction increases the functional residual capacity.

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

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

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

The 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 larynx is an air passage, sphincter, and organ of phonation that extends from the tongue to the trachea. It lies in the anterior part of the neck at the vertebral levels C3 to C6.

Important anatomical landmarks:
C1-C2 – Atlas and axis, respectively

C3-C6 – Larynx

C5 – Thyroid cartilage

T5-T7 – Pulmonary hilum

T12-L1 – Duodenum.

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

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

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

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

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

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

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

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

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

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

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

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

The inferior mesenteric artery arises from the abdominal aorta at the level of the L3 vertebrae and supplies blood to the final third of the transverse colon, the descending colon, the sigmoid colon and the uppermost part of the rectum.

It is the artery most likely to affect the left colon.

A forest plot is a graphical representation that summarizes the findings of several research, such as a meta-analysis of a series of randomized controlled trials.

The Kaplan-Meier estimate shows survival over time, for example, plotting the number of patients still alive seven years after chemotherapy for lung cancer.

Fisher’s exact test similarly uses contingency tables to assess statistical significance, however, it is typically used when sample sizes are small.

Chi-square test assesses whether an association exists between two categorical variables using the observed and expected frequencies. For instance, is social class (I-V) related to body mass index (BMI) category? Using the observed and anticipated frequencies, the Chi-square test determines whether a connection exists between two categorical variables. For example, is socio-economic status related to BMI category?

Linear regression is a technique which attempts to model the relationship between two variables by fitting a linear equation to observed data. Linear regression uses correlation between two continuous variables. As correlation only indicates the strength of an association only, it cannot be used to forecast the change in one variable when a second variable is altered.

This equation takes the form y = mx + c, where ‘y’ is the dependent variable, ‘x’ is the independent variable, ‘m’ is the slope of the line and ‘c’ is the intercept. In this example, for a range of heights, it would be possible to map a line of best fit to a scatter plot and thus predict the forced expiratory volume (FEV1) for an individual.

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.

68% of the population will be found in one standard deviation (SD) above plus one SD below the mean. Two SDs above plus two SDs below the mean will include 95% of the population.

The median can be greater or less than the mean as it is simply the mid point of the data after the data is arranged. Half the data are above and half below the median .

The mode is a true score, unlike the mean or the median. It is the most common score or the score obtained from the largest number of subjects in any given data.