ACTH production is stimulated through the secretion of corticotropin-releasing hormone (CRH) from the hypothalamic nuclei.

ACTH secretion has a circadian rhythm. A high level of cortisol in the body stops its production. ACTH is secreted maximally in the morning and concentrations are lowest at midnight.

ACTH can be expressed in the placenta, the pituitary and other tissues.

Conditions where ACTH concentrations rise include: stress, disease and pregnancy.

Glucocorticoids (not mineralocorticoids – aldosterone) switch off ACTH production through a negative feedback loop .

Soda-lime contains mostly calcium hydroxide (about 94%) and remaining sodium hydroxide.

CO2 + Ca(OH)2 → CaCO3 + H2O + heat
Here in this exothermic reaction, we can see that the production of calcium carbonate does not require heat.

When soda lime is allowed to dry with subsequent use of desflurane, isoflurane, and enflurane, it can lead to the generation of carbon monoxide.

Silica hardens the granules and can thus prevent disintegration.

The size of soda-lime granules is 4-8 mesh because it allows sufficient surface area for chemical reaction to occur without critically increasing the resistance to airflow.

The posterior tibial nerve lies on the posterior surface of the tibialis posterior and, lower down the leg, on the posterior surface of the tibia. The nerve accompanies the posterior tibial artery and lies at first on its medial side, then crosses posterior to it, and finally lies on its lateral side. The nerve, with the artery, passes behind the medial malleolus, between the tendons of the flexor digitorum longus and the flexor hallucis longus.

It gives off muscular branches to the soleus, flexor digitorum longus, flexor hallucis longus, and tibialis posterior. A medial calcaneal branches off to supply the skin over the medial surface of the heel, and an articular nerve to supply the ankle joint. Finally, it terminates to become the medial and lateral plantar nerves.

The saphenous nerve is a branch of the femoral nerve that gives off branches that supply the skin on the posteromedial surface of the leg.

The sural nerve is a branch of the tibial nerve that supplies the skin on the lower part of the posterolateral surface of the leg.

The superficial peroneal nerve is one of the terminal branches of the common peroneal nerve. It arises in the substance of the peroneus longus muscle on the lateral side of the neck of the fibular. It ascends between the peroneus longus and brevis muscles, and in the lower part of the leg it becomes cutaneous. Muscular branches of the superficial peroneal nerve supply the peroneus longus and brevis muscles, while medial and lateral cutaneous branches are distributed to the skin on the lower part of the leg and dorsum of the foot. In addition, the cutaneous branches supply the dorsal surfaces of the skin of all the toes, except the adjacent sides of the first and second toes and the lateral side of the little toe.

The superficial peroneal, sural and saphenous nerves cannot be used to assess neuromuscular blocks since they are sensory nerves.

The deep peroneal nerve enters the dorsum of the foot by passing deep to the extensor retinacula on the lateral side of the dorsalis pedis artery. It divides into terminal, medial, and lateral branches. The medial branch supplies the skin of the adjacent sides of the big and second toes. The lateral branch supplies the extensor digitorum brevis muscle. Both terminal branches give articular branches to the joints of the foot. This nerve is too deep to use for neuromuscular blockade assessment

The glucose molecule enters the Bowman’s capsule freely and becomes part of the filtrate.

All glucose is reabsorbed in the proximal convoluted tubule when blood glucose concentrations are below a certain threshold (approximately 11 mmol/L) (PCT). Active transportation makes this possible. In the proximal tubular cells, sodium/glucose cotransporters (SGLT1 and SGLT2) are the proteins responsible.

Glucose does not normally appear in the urine below the renal threshold.

The renal glucose threshold is not set in stone and is affected by a variety of factors, including GFR, TmG, and the quantity of splay.

The different absorptive and filtering capacities of individual nephrons cause splay, which is the rounding of a glucose reabsorption curve.

The SGLT proteins have a high affinity for glucose, but not an infinite affinity. As a result, some glucose may escape reabsorption before the TmG. A decrease in renal threshold may be caused by an increase in splay.

Because the filtered glucose load is reduced and the PCT can reabsorb all of the filtered glucose despite hyperglycaemia, a low GFR causes an increase in TmG. In contrast, lowering the TmG lowers the threshold because the tubules’ ability to reabsorb glucose is reduced.

A reduction in GFR caused by severe dehydration and reduced perfusion pressure is the most obvious cause of the discrepancy between plasma and urinary glucose in this scenario.

During normal tissue metabolism, there is production of CO2 (acid) which is then expired by the lungs. If metabolism switches from aerobic to anaerobic due to a lack of oxygen, the tissues are unable to completely oxidise sugars to CO2. As a consequence, the sugars can only be partially oxidised to lactic acid. Since lactic acid cannot be expired by the lungs, it remains in the circulation leading to metabolic acidosis.

Also, normal tissue metabolism leads to the production of some amount of acid from the breakdown of proteins. These acids are excreted from the body by kidney filtration. Renal failure will therefore results in acidosis after several days.

An increased acidosis stimulates the brain’s respiratory centres to increase the respiratory rate. This lowers the CO2 in the blood, leading to a decrease in its acidity. Renal excretion removes the excess acid, resulting in a normal pH, and a reduced PaCO2 and HCO3.

pH PaCO2 (kPa) HCO3
Compensated respiratory acidosis 7.34 7.2 29
Acute respiratory acidosis 7.25 7.3 22
Compensated metabolic acidosis 7.34 3.6 14
Metabolic acidosis 7.21 5.3 15
Metabolic alkalosis 7.51 5.1 30

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.

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.

Each kidney is composed of about 1.2 million uriniferous tubules. Each tubule consists of two parts that are embryologically distinct from each other. They are as follows:
a) Excretory part, called the nephron, which elaborates urine
b) Collecting part which begins as a junctional tubule from the distal convoluted tubule.

There are two types of nephrons in the kidney:
The cortical nephron comprises 80% of the total nephron and its major function is the excretion of waste products in urine whereas the juxtamedullary nephron comprises 20% of the total nephron and its major function is the concentration of urine by counter current mechanism.
In the superficial (cortical) nephrons, peritubular capillaries branch off the efferent arterioles and deliver nutrients to epithelial cells as well as serve as a blood supply for reabsorption and secretion. In juxtamedullary nephrons, the peritubular capillaries have a specialization called the vasa recta, which are long, hairpin-shaped blood vessels that follow the same course as a loop of Henle. The vasa recta serve as osmotic exchangers for the production of concentrated urine.

The kidney receives about 25% of cardiac output and about 20% of this is filtered at the glomeruli of the kidney. Thus, renal blood flow is 1200 ml/minute and renal plasma flow is 650 ml/minute

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 umbilical vein closes once the umbilical cord is clamped following birth. This causes a rise in systemic vascular resistance, closing the ductus venosus.

Upon birth, the pulmonary vascular resistance is decreased as the lungs are aerated.

At birth, there is a rise in oxygen tension which causes the corresponding constriction of the ductus arteriosus. This prevents a left to right shunt as it stops aortic blood and blood from the pulmonary artery from mixing. The ventricles do no have an opening connecting them.

The foramen ovale closes soon after birth. It is the septum opening between the left and right atrium.

An adult’s cardiac output is expected to be 5 L/min

Gas is composed of large numbers of molecules moving in random directions, separated by distances. They undergo perfectly elastic collisions with each other and the walls of a container and transfer kinetic energy in form of heat. These assumptions bring the characteristics of gases within the range and reasonable approximation to a real gas, particularly how any change in temperature and pressure affect the behaviour of gas. According to different theories and laws proposed, mathematical equations are derived to calculate the volume of gas, also different abbreviations are being used according to given conditions. The abbreviations used are ATP, BTPS, and STPD.
ATP stands for ambient temperature and barometric pressure, it is used to describe the conditions under which volume of gas is measured.
BTPS stands for body temperature and pressure saturated with water vapor. These are conditions under which volume of gas exist and all results of lung volume determination should be quoted at BTPS.
STPD stands for standard temperature and pressure, dry (0C and 760 mm Hg). These are the conditions that are used to describe quantities of individual gases exchanged in the lungs.

The electrons in the outer shell of an oxygen molecule are unpaired, thus it has paramagnetic properties and is attracted into a magnetic field.

It utilizes null deflection -True
Null deflection is a crucial principle in paramagnetic analysers (reflected beam of light on two photocells) which gives very accurate results (typically 0.1%).

It can be used to measure the concentration of diamagnetic gases – False
Since most other gases are weakly diamagnetic they are repelled by a magnetic field (nitric oxide is also paramagnetic).

Can measure gases dissolved in the blood – False
For accurate analysis the sample gas must be dried before passing into the analysis cell, for example, by passage through silica gel. Therefore, they are unsuitable to measure gases dissolved in blood.

Does not require calibration – False
As with most measurement instruments paramagnetic analysers must be calibrated before use.

E) The readings are unaffected by water vapour – False
Water vapour affects the readings hence for accurate analysis the sample gas must be dried before passing into the analysis cell, for example, by passage through silica gel. That is why they are unsuitable to measure dissolved blood gases.

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

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

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

The principle by which a strain gauge works is that when a wire is stretched, it becomes longer and thinner, and as a result, its resistance increases.

A strain gauge, which is used in pressure transducers, acts as a resistor. When the pressure in a pressure transducer changes, the diaphragm moves, changing the tension in the resistance wire and thus changing the resistance.

Changes in current flow through the resistor are amplified and displayed as a pressure change measure.

A Wheatstone bridge, on the other hand, is frequently used to measure or monitor these changes in resistance.

The positive predictive value is the ratio of patients truly diagnosed as positive to all those who had positive test results. In this case, this is 60/(60+20)=75%.

The negative predictive value is the ratio of patients truly diagnosed as negative to all those who had negative test results. In this case, this is 80/(80+40)=67%.

The sensitivity is the ratio of patients with the disease who test positive i.e. true positive patients to the total number of people with the disease. In this case, this is 60/(60+40)=60%.

The specificity is the ratio of people who don’t have the disease who test negative i.e. true negatives to the total number of people without the disease. In this case, this is 80/(20+80)=80%.

70% is not the result of any screening measurements

It is well known that atropine will cross the placenta and that maternal administration results in an increase in fetal heart rate.

Atropine is highly selective for muscarinic receptors. Its potency at nicotinic receptors is much lower, and actions at non-muscarinic receptors are generally undetectable clinically. Atropine does not distinguish among the M1, M2, and M3 subgroups of muscarinic receptors. In contrast, other antimuscarinic drugs are moderately selective for one or another of these subgroups. Most synthetic antimuscarinic drugs are considerably less selective than atropine in interactions with nonmuscarinic receptors.

A study on glycopyrrolate, a quaternary ammonium salt, was found to have a fetal: maternal serum concentration ratio of 0.4 indicating partial transfer.

Heparin, suxamethonium, and vecuronium do not cross the placenta.

Noradrenaline has a short half-life of about 2 minutes. It is rapidly cleared from plasma by a combination of cellular reuptake and metabolism.

It acts as sympathomimetics by acting on ?1 receptors and also on ? receptors.

It decreases renal and hepatic blood flow.

Norepinephrine is metabolized by the enzymes monoamine oxidase and catechol-O-methyltransferase to 3-methoxy-4-hydroxymandelic acid and 3-methoxy-4-hydroxyphenylglycol (MHPG).

Natural catecholamines are Adrenaline, Noradrenaline, and Dopamine

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.

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.

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.

Level 1 – High-quality randomised controlled trial with statistically significant difference or no statistically significant difference but narrow confidence intervals (prospective controlled)

Level 2 – Prospective comparative study (prospective uncontrolled)

Level 3 – Case-control study, retrospective comparative study (retrospective controlled)

Level 4 – Case series (retrospective uncontrolled)

Level 5 – Expert opinion.

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.

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)

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..

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

A major source of caloric expenditure and oxygen consumption in the body is work of breathing (WOB) and 70% of this is to overcome elastic forces. The remaining 30% is for flow-resistive work

In a normal patient breathing normally, the total area of hysteresis pressure volume curve represents the flow-resistive WOB.

The area of the expiratory resistive work increases during an asthma attack making the compliance curve larger in area. The larger the area the greater the work required to breathe.

The leading cause of perioperative anaphylaxis in the UK currently are antibiotics. They account for 46% of cases with identified causative agents. Co-amoxiclav and teicoplanin between them account for 89% of antibiotic-induced perioperative anaphylaxis

Neuromuscular blocking agents (NMBAs) are the second leading cause and account for 33% of case.

Chlorhexidine (0.78/100,000 administrations)
Co-amoxiclav (8.7/100,000 administrations)Suxamethonium (11.1/100,000 administrations)
Patent blue dye (14.6/100,000 administrations)
Teicoplanin (16.4/100,000 administrations)

Anaphylaxis to chlorhexidine periop poses a significant risk in the healthcare setting because of its widespread use with some being fatal.

The clinical signs suggest a class II haemorrhage – 15-30% of circulating blood volume has been lost.

Pelvic fractures are associated with significant concealed haemorrhage (>2000 ml) and may require aggressive fluid resuscitation. Other priorities include stabilisation of the fracture(s) and pain relief.

The Advanced Trauma Life Support (ATLS) classification of haemorrhagic shock is as follows:

Class I haemorrhage (blood loss up to 15%):
<750 ml of blood loss
Minimal tachycardia
No changes in blood pressure, RR or pulse pressure
Normally not require fluid replacement as will be restored in 24 hours, but in trauma correct.

Class II haemorrhage (15-30% blood volume loss):
Uncomplicated haemorrhage requiring crystalloid resuscitation
Represents about 750 – 1500 ml of blood loss
Tachycardia, tachypnoea and a decrease in pulse pressure (due to a rise in diastolic component due action of catecholamines)
Minimal systolic pressure changes
Anxiety, fright or hostility
Can usually be stabilised by crystalloid, but may later require a blood transfusion.

Class III haemorrhage (30-40% blood volume loss):
Complicated haemorrhagic state in which at least crystalloid and probably blood replacement are required
Classical signs of inadequate perfusion, marked tachycardia, tachypnoea, significant changes in mental state and measurable fall in systolic pressure
Almost always require blood transfusion, but decision based on patient initial response to fluid resuscitation.

Class IV haemorrhage (> 40% blood volume loss):
Preterminal event patient will die in minutes
Marked tachycardia, significant depression in systolic pressure and very narrow pulse pressure (or unobtainable diastolic pressure)
Mental state is markedly depressed
Skin cold and pale
Need rapid transfusion and immediate surgical intervention.

Loss of >50% results in loss of consciousness, pulse and blood pressure.

The route of choice is an arm vein (cephalic) with one or two large bore cannula. This will enable initial aggressive fluid resuscitation. A central line can be inserted at a later stage if central venous monitoring is deemed necessary. If a suitable peripheral vein cannot be cannulated with a large bore cannula then the internal jugular vein could be accessed rapidly (preferably ultrasound guided).

Intravenous access below the diaphragm in this case is inadvisable when other routes are available.

Pulmonary vascular resistance (PVR) refers to the resistance to blood flow to the left atrium from the pulmonary artery.
It is derived mathematically by:

PVR = MPAP – PCWP
CO
where,
MPAP: Mean pulmonary artery pressure
PCWP: Pulmonary capillary occlusion pressure
CO: Cardiac output

For this patient:
PVR = 10 – 5 = 1mmHg
5

Remember, multiply by correction factor 80 to change units:

PVR = 1mmHg x 80 = 80 dynes·s·cm-5

Normal values range between 20-130 dynes·s·cm-5

The popliteal fossa is the shallow, diamond-shaped depression located in the back of the knee joint.

The structures that lie within in from superficial to deep are:

The tibial and common fibular nerve: Most superficial. They arise from the sciatic nerve.
The popliteal vein
The popliteal artery: Lies deepest. It arises from the femoral artery

Boundaries of the popliteal fossa:

Laterally
Biceps femoris above, lateral head of gastrocnemius and plantaris below

Medially
Semimembranosus and semitendinosus above, medial head of gastrocnemius below

Floor
Popliteal surface of the femur, posterior ligament of knee joint and popliteus muscle

Roof
Superficial and deep fascia