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 normal distribution is a symmetrical, bell-shaped distribution in which the mean, median and mode are all equal.

The respiratory quotient is the ratio of CO2 produced to O2 consumed while food is being metabolized:

RQ = CO2 eliminated/O2 consumed

Most energy sources are food containing carbon, hydrogen and oxygen. Examples include fat, carbohydrates, protein, and ethanol. The normal range of respiratory coefficients for organisms in metabolic balance usually ranges from 1.0-0.7.

Granulated sugar is a refined carbohydrate with no significant fat, protein or ethanol content.

The RQ for carbohydrates is = 1.0

The RQ for the rest of the compounds are:

Fats RQ = 0.7
The chemical composition of fats differs from that of carbohydrates in that fats contain considerably fewer oxygen atoms in proportion to atoms of carbon and hydrogen.

Protein RQ = 0.8
Due to the complexity of various ways in which different amino acids can be metabolized, no single RQ can be assigned to the oxidation of protein in the diet; however, 0.8 is a frequently utilized estimate.

Sensory innervation of the larynx is controlled by branches of the vagus nerve.

The internal and external bifurcations of the superior laryngeal nerve is responsible for sensory innervation of the aspect of the larynx superior to the vocal cords, while the recurrent laryngeal nerve is responsible for sensory innervation of the intrinsic musculature of the larynx except for the cricothyroid muscle.

The 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.

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

Barbiturates are derived from barbituric acid, which itself is nondepressant, but appropriate side-chain substitutions result in CNS depressant activity that varies in potency and duration with carbon chain length, branching, and saturation.

Oxybarbiturates retain an oxygen atom on number 2-carbon atom of the barbituric acid ring.

Thiobarbiturates replace this oxygen atom with a sulphur atom, which confers greater lipid solubility. Generally speaking, a substitution such as sulphuration that increases lipid solubility is associated with greater hypnotic potency and more rapid onset, but shorter duration of action.

Addition of a methyl group to the nitrogen atom of the barbituric acid ring, as with oxybarbiturate methohexital, also results in a compound with a short duration of action.

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.

The area described in the question is supplied by the intercostobrachial nerve, which provides sensory innervation to the portions of the axilla, tail of the breast, lateral chest wall and medial side of the arm.

It is a common for it to be ‘missed’ during administration of local anaesthesia because of its very superficial anatomic course. It may be anesthetized by giving an analgesia from the upper border of the biceps at the anterior axillary fold, to the margin of the triceps by the axillary floor.

Only on rare occasions has it been found that the prevalence and incidence were same. Incidence can be greater than prevalence in acute cases only. In case of chronic diseases prevalence is far greater than incidence. One needs to have a deeper understanding of both the concepts to understand the health literature.

Tramadol is weak agonist at the mu receptor. It inhibits the neuronal reuptake of serotonin and norepinephrine, and inhibits pain neurotransmission. It is given for moderate pain, chronic pain syndromes, and neuropathic pain.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI). It inhibits the neuronal reuptake of serotonin by inhibiting the serotonin transporter (SERT). It is the drug of choice for major depressive disorder, and is given for other psychiatric disorders such as anxiety, obsessive-compulsive, post-traumatic stress, and phobias.

When tramadol is given with SSRIs, serotonin syndrome may occur. Serotonin syndrome is characterized by fever, agitation, tremors, clonus, hyperreflexia and diaphoresis. The onset of symptoms may occur within a few hours, and the first-line treatment is sedation, paralysis, intubation and ventilation.

Epoprostenol has a half-life of only 42 seconds and has rapid offset. It is used for the treatment of pulmonary hypertension.

Aspirin inhibits the COX enzyme irreversibly. It inhibits thromboxane synthesis but does not inhibit the enzyme thromboxane synthetase.

Ticlopidine, clopidogrel and prasugrel act as irreversible antagonists of P2 Y12 receptor of Adenosine Diphosphate (ADP). These drugs interfere with the activation of platelets by ADP and fibrinogen. Both aspirin and clopidogrel act irreversibly so they are not correct.

Paclitaxel is a long-acting antiproliferative agent used for the prevention of restenosis (recurrent narrowing) of coronary and peripheral stents and is not the correct answer.

Tirofiban has the next shortest duration of action after epoprostenol. If epoprostenol is not given in the question, it would be the best answer.

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.

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

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

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

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.

The peritoneal cavity is made up of the omentum, the ligaments and the mesentery.

The section of the peritoneum responsible for tethering organs to the posterior abdominal wall is the mesentery.

These tethered organs are classified as intraperitoneal, and these include the stomach, spleen, liver, first and fourth parts of the duodenum, jejunum, ileum, transverse, and sigmoid colon.

Retroperitoneal organs are located posterior to the peritoneum and include: the rest of the duodenum, the ascending colon, the descending colon, the middle third of the rectum, and the remainder of the pancreas

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.

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= (43.9-37.3)

ARR= 6.6

NNT= 1000/6.6

NNT=151.5

There are different classes of electrical equipment that can be classified in the table below:

Class 1 – provides basic protection only. It must be connected to earth and insulated from the mains supply

Class II – provides double insulation for all equipment. It does not require an earth.

Class III – uses safety extra low voltage (SELV) which does not exceed 24 V AC. There is no risk of gross electrocution but risk of microshock exists.

Type B – All of above with low leakage currents (0.5mA for Class IB, 0.1 mA for Class IIB)

Type BF – Same as with other equipment but has ‘floating circuit’ which means that the equipment applied to patient is isolated from all its other parts.

Type CF – Class I or II equipment with ‘floating circuits’ that is considered to be safe for direct connection with the heart. There are extremely low leakage currents (0.05mA for Class I CF and 0.01mA for Class II CF)

Wavelength can be computed as follows:

Wavelength = velocity/frequency

In the given problem, the values stated are:

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

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

The concentration of solute particles per litre (mosm/L) = the osmolarity of a solution. Changes in water content, ambient temperature, and pressure affects osmolarity. The osmolarity of any solution can be calculated by adding the concentration of key solutes in it.

Individual manufacturers of crystalloids and colloids may have different absolute values but they are similar to these.

0.45% N. Saline with 5% glucose:
Tonicity – hypertonic
Osmolarity – 405 mosm/L
Kilocalories (kCal) – 107

0.9% N. Saline:
Tonicity – isotonic
Osmolarity – 308 mosm/L
Kilocalories (kCal) – 0

5% Dextrose:
Tonicity – isotonic
Osmolarity – 253 mosm/L
Kilocalories (kCal) – 170

Gelofusine (154 mmol/L Na, 120 mmol/L Cl):
Tonicity – isotonic
Osmolarity – 274 mosm/L
Kilocalories (kCal) – 0

Hartmann’s solution:
Tonicity – isotonic
Osmolarity – 273 mosm/L
Kilocalories (kCal) – 9

Unionised molecules are more likely than ionised molecules to cross membranes (such as the blood-brain barrier).

Because alfentanil and fentanyl are weak bases, the Henderson-Hasselbalch equation says that the ratio of ionised to unionised molecules is determined by the parent compound’s pKa in relation to physiological pH.

Alfentanil has a pKa of 6.5, while fentanyl has a pKa of 8.4.
At a pH of 7.4, 89 percent of alfentanil is unionised, whereas 9% of fentanyl is.

As a result, alfentanil has a faster onset than fentanyl.

Fentanyl is 83% plasma protein bound
Alfentanil is 90% plasma protein bound.

Alfentanil’s pharmacokinetics are affected by its higher plasma protein binding. Because alfentanil has a low hepatic extraction ratio (0.4), clearance is determined by the degree of protein binding rather than the time it takes to take effect.

Phenytoin, Carbamazepine, and Valproate act by inhibiting the sodium channels when these are open. These drugs also prolong the inactivated stage of these channels (Sodium channels are refractory to stimulation till these reach the closed/ resting phase from inactivated phase)

Carbamazepine is the drug of choice for partial seizures and trigeminal neuralgia

It can have neurotoxic side effects. Major neurotoxic effects include dizziness, headache, ataxia, vertigo, and diplopia

After single oral doses of carbamazepine, the absorption is fairly complete and the elimination half-life is about 35 hours (range 18 to 65 hours). During multiple dosing, the half-life is decreased to 10-20 hours, probably due to autoinduction of the oxidative metabolism of the drug.

It is metabolized in liver into active metabolite, carbamazepine-10,11-epoxide.

With regards to the autonomic nervous system (ANS)

1. It is not under voluntary control
2. It uses reflex pathways and different to the somatic nervous system.
3. The hypothalamus is the central point of integration of the ANS. However, the gut can coordinate some secretions and information from the baroreceptors which are processed in the medulla.

With regards to the central nervous system (CNS)
1. There are myelinated preganglionic fibres which lead to the
ganglion where the nerve cell bodies of the non-myelinated post ganglionic nerves are organised.
2. From the ganglion, the post ganglionic nerves then lead on to the innervated organ.

Most organs are under control of both systems although one system normally predominates.

The nerves of the sympathetic nervous system (SNS) originate from the lateral horns of the spinal cord, pass into the anterior primary rami and then pass via the white rami communicates into the ganglia from T1-L2.

There are short pre-ganglionic and long post ganglionic fibres.
Pre-ganglionic synapses use acetylcholine (ACh) as a neurotransmitter on nicotinic receptors.
Post ganglionic synapses uses adrenoceptors with norepinephrine / epinephrine as the neurotransmitter.
However, in sweat glands, piloerector muscles and few blood vessels, ACh is still used as a neurotransmitter with nicotinic receptors.

The ganglia form the sympathetic trunk – this is a collection of nerves that begin at the base of the skull and travel 2-3 cm lateral to the vertebrae, extending to the coccyx.

There are cervical, thoracic, lumbar and sacral ganglia and visceral sympathetic innervation is by cardiac, coeliac and hypogastric plexi.

Juxta glomerular apparatus, piloerector muscles and adipose tissue are all organs under sole sympathetic control.

The PNS has a craniosacral outflow. It causes reduced arousal and cardiovascular stimulation and increases visceral activity.

The cranial outflow consists of
1. The oculomotor nerve (CN III) to the eye via the ciliary ganglion,
2. Facial nerve (CN VII) to the submandibular, sublingual and lacrimal glands via the pterygopalatine and submandibular ganglions
3. Glossopharyngeal (CN IX) to lungs, larynx and tracheobronchial tree via otic ganglion
4. The vagus nerve (CN X), the largest contributor and carries ¾ of fibres covering innervation of the heart, lungs, larynx, tracheobronchial tree parotid gland and proximal gut to the splenic flexure, liver and pancreas

The sacral outflow (S2 to S4) innervates the bladder, distal gut and genitalia.

The PNS has long preganglionic and short post ganglionic fibres.
Preganglionic synapses, like in the SNS, use ACh as the neuro transmitter with nicotinic receptors.
Post ganglionic synapses also use ACh as the neurotransmitter but have muscarinic receptors.

Different types of these muscarinic receptors are present in different organs:
There are:
M1 = pupillary constriction, gastric acid secretion stimulation
M2 = inhibition of cardiac stimulation
M3 = visceral vasodilation, coronary artery constriction, increased secretions in salivary, lacrimal glands and pancreas
M4 = brain and adrenal medulla
M5 = brain

The lacrimal glands are solely under parasympathetic control.

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

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

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

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.

There are different models of flowmeters determined by the applied pressure and its orifice. For instance, the watersight flowmeter functions through applying variable pressure, and it has a variable orifice. In contrast, the bubble flowmeter is operated using a constant pressure and orifice. Flowmeters such as rotameters, Heidbrink and Peak have a constant pressure but variable orifice. On the other hand, flowmeters including a simple pressure gauge, water depression, and pneumotachograph have a constant orifice but variable pressure.

A patient presenting with symptomatic asthma should be assessed for severity to determine appropriate management options. Indications of acute severe asthma are:

Peak expiratory flow rate (PEFR): 33-50% best/predicted
Respiratory rate: ≥25/min
Heart rate: ≥110/min
Inability to finish a complete sentence in a single breath.

Oxygen saturation should be measured. Any measurement of an oxygen saturation of 92% or less, either on air or on oxygen, indicates severe, life threatening asthma, and requires an arterial blood gas (ABG) to detect normo- or hypercarbia.

A chest x-ray would not be routine as it will not provide any relevant information. It is only required in specific cases, including:
Diagnosis of a subcutaneous emphysema
Indications of a unilateral pneumothorax
Indications of a lobar collapse of consolidation
Treatment-resistance life-threatening asthma
If mechanical ventilation is indicated

A peak expiratory flow rate (PEFR) can provide relevant information to help distinguish between acute, moderate, severe and life threatening asthma. However, it is not necessary as other parameters exist that can also help make the same distinction.

An ECG is indicated in this case as the patient has tachycardia and tachypnoea which are indicative of acute severe asthma. The ECG would indicate if arrhythmia is also present which would suggest life-threatening asthma.

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.