The patient’s diagnosis is microcytic hypochromic anaemia which is often as a result of iron deficiency and thalassaemia.

Macrocytic anaemia is often caused by folate and B12 deficiencies and alcohol abuse.

Normocytic normochromic anaemia is often caused by acute blood loss, haemolytic anaemia, anaemia of chronic disease and leucoerythroblastic anaemias.

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.

Tests are used to confirm the presence of a particular disease. However the results can be misleading at times since most of the tests have some limitations associated with them.
Sensitivity is the correct term that refers to the probability of a positive test. The others are explained below:

False Positive rates refer to the proportion of the patients who don’t have the condition being detected as positive.

False Negative rates refer to the proportion of the patients who have the condition being detected as negative (like the 20% of the patients that went undetected by the Ca-125 test).

Specificity describes the ability of a test to detect and pick up people without the disease. Absolute risk ratio compares the rate of two separate outcomes.

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 (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

During glycolysis, 2,3-diphosphoglycerate (2,3-DPG) is
created in erythrocytes by the Rapoport-Luebering shunt.

The production of 2,3-DPG increases for several conditions
in the presence of decreased peripheral tissue O2 availability.
Some of these conditions include hypoxaemia, chronic lung
disease anaemia, and congestive heart failure. Thus,
2,3-DPG production is likely an important adaptive mechanism.

High levels of 2,3-DPG cause a shift of the curve to the right.
Low levels of 2,3-DPG cause a shift of the curve to the left,
as seen in states such as septic shock and hypophosphatemia.

The following table shows the compartments and their relative oxygen reserve:
Compartment Factors Room air (mL) 100% O2 (mL)
Lung FAO2, FRC 630 2850
Plasma PaO2, DF, PV 7 45
Red blood cells Hb, TGV, SaO2 788 805
Myoglobin 200 200
Interstitial space 25 160

Oxygen reserves in the body, with room air and after oxygenation.

FAO2-alveolar fraction of oxygen rises to 95% after administration of 100% oxygen (CO2 = 5%)
FRC- Functional residual capacity – (the most important store of oxygen in the body) – 2,500-3,000 mL in medium sized adults
PaO2-partial pressure of oxygen dissolved in arterial blood (80 mmHg breathing room air and 500 mmHg breathing 100% oxygen)
DF -dissolved form (0.3%)
PV-plasma volume (3L)
TG-total globular volume (5L)
Hb-haemoglobin concentration
SaO2-arterial oxygen concentration (98% breathing air and 100% when preoxygenated)

Half life (T½) is the time required to change the amount of drug in the body by one-half (or 50%) during elimination. The time course of a drug in the body will depend on both the volume of distribution and the clearance.

Extrapolating the values from the plasma concentration vs time:

Plasma concentration at 0 hours = 800 mcg/mL
Plasma concentration at 2 hours = 400 mcg/mL
Plasma concentration at 4 hours = 200 mcg/mL
Plasma concentration at 6 hours = 100 mcg/mL
Plasma concentration at 8 hours = 50 mcg/mL
Plasma concentration at 10 hours = 25 mcg/mL
Plasma concentration at 12 hours = 12.5 mcg/mL
Plasma concentration at 14 hours = 6.25 mcg/mL

To begin, one must determine the child’s approximate weight. There are a variety of formulas to choose from. It is acceptable to use the advanced paediatric life support formula:

(age + 4) 2 = weight

A 5-year-old child will weigh around 18 kilogrammes.

The following are the appropriate doses of the drugs listed above:

Gentamicin (once daily) – 5-7 mg/kg = 90-126 mg and subsequent dose modified according to plasma levels
Ondansetron – 0.1 mg/kg, but a maximum of 4 mg as a single dose = 1.8 mg
Codeine should be administered orally at a dose of 1 mg/kg rather than intravenously, as the latter can cause ‘dangerous’ hypotension due to histamine release.
15 mg/kg paracetamol = 270 mg orally or intravenously (a loading dose of 20 mg/kg, or 360 mg, is sometimes recommended, which is not far short of the doses listed above).
Cefuroxime – the initial intravenous dose is 20 mg/kg (360 mg) depending on the indication (again, similar to the dose given in the answer options above).

In patients with an intact hypothalamic-pituitary axis, serial TSH measurements are used to determine the adequacy of treatment with thyroid hormones . changes in TSH levels becoming apparent after approximately eight weeks of therapy with thyroid hormone replacement. Change in T3/T4 levels are seen before changes in TSH .

In patients taking thyroid replacement therapy, the most frequent reason for persistent elevation of serum TSH is poor compliance. Patients who do not regularly take their L-thyroxine try and catch up just before a visit to a clinician for blood test.

Tissue-level unresponsiveness to thyroid hormone is caused by mutation in the gene controlling a receptor for T3 and is rare.

Reduced responsiveness of target tissues to thyroid hormone aka resistance to thyroid hormones (rTH) occurs when there is a mutation in the thyroid hormone receptor ? gene. It is a rare autosomal dominant inherited syndrome of reduced end-organ responsiveness to thyroid hormone and has two types:

Generalised resistance (GrTH)
Pituitary resistance (PrTH)

Patients with rTH have normal or slightly elevated serum thyroid stimulating hormone (TSH) level, elevated serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations.

Drugs that increase metabolism of thyroxine include:

Warfarin
Rifampin
Phenytoin
Phenobarbital
St John’s Wort
Carbamazepine

These drugs lower circulating thyroid hormones and would be associated with a raised TSH but low T3/T4.

Because the patient has mild systemic disease, he is ASA 2 and the procedure will be performed under local anaesthesia.

The following factors should be considered when requesting preoperative investigations:

Indications derived from a preliminary clinical examination
Whether or not a general anaesthetic will be used, the possibility of asymptomatic abnormalities, and the scope of the surgery.

No special investigations are needed if the patient has no history of significant systemic disease and no abnormal findings on examination during the nurse-led assessment.

Standard wire gauge cannulas for intravenous and intraarterial use are available (SWG or G). The SWG is a former imperial unit (which requires metric conversion). The cross sectional area of wires is becoming more popular as a size measurement.

The number of wires that will fit into a standard hole template is referred to as SWG.

This standard sized hole can accommodate 22 thin wires side by side (each wire the diameter of a 22 gauge cannula)
In the same hole, 14 thicker wires would fit (each wire the diameter of a 14 gauge cannula)

While the diameter and thus radius of a parallel sided tube are the most important determinants of fluid flow rate, they are not commonly used to compare cannula sizes.

The circumference of French gauge (FG) catheters (urinary or chest drains) is measured. Sizes of double lumen tracheal tubes are FG. Internal diameter is used to measure single lumen tubes.

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.

The derived SI unit of force is Newton.
F = m·a (where a is acceleration)
F = 1 kg·m/s2

The joule (J) is a converted unit of energy, work, or heat. When a force of one newton (N) is applied over a distance of one metre (Nm), the following amount of energy is expended:

J = 1 kg·m/s2·m =
J = 1 kg·m2/s2 or 1 kg·m2·s-2

The unit of velocity is metres per second (m/s or ms-1).

The watt (W), or number of joules expended per second, is the SI unit of power:

J/s = kg·m2·s-2/s
J/s = kg·m2·s-3

Pressure is measured in pascal (Pa) and is defined as force (N) per unit area (m2):
Pa = kg·m·s-2/m2
Pa = kg·m-1·s-2

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.

The fibrotendinous ring formed by the congregation of the rectus muscles at the apex of the orbit does not include superior oblique. This muscle is completely outside the ring and so it is the most difficult muscle to anaesthetise completely. A good grasp of the anatomy of the area being anaesthetised is important with all regional anaesthetic techniques so that potential problems and complications with a block can be anticipated.

The borders of this pyramid whose apex points upwards and outwards of the bony orbit are as follows:
Floor – Zygoma and Maxilla
Roof – frontal bone
Medial wall – maxilla, ethmoid, sphenoid and lacrimal bones.
Lateral wall – greater wing of the sphenoid and the zygoma.

The four recti muscles (superior, medial, lateral and inferior) originate from a tendinous ring (the annulus of Zinn) and extend anteriorly to insert beyond the equator of the globe. Bands of connective tissue are present between the rectus muscles forming a conical structure and hinder the passage of local anaesthetic.

The superior oblique muscle is situated outside this ring and is the most difficult muscle to anaesthetise completely, particularly with a single inferotemporal peribulbar injection. An additional medial injection may help to prevent this.

The cranial nerve supply to the extraocular muscles are:
3rd (inferior oblique, inferior recti, medial and superior)
4th (superior oblique), and
6th (lateral rectus).

The long and short ciliary nerves provide the sensory supply to the globe and these are branches of the nasociliary nerve, (which is itself a branch of the ophthalmic division of the trigeminal nerve).

To achieve anaesthesia for the eye, these nerves which enter the fibrotendinous ring need to be fully blocked to anaesthetise the eye for surgery.

The occlusion of the left anterior descending (LAD) coronary artery causes anterior ST elevation myocardial infarction (STEMI). It has the worst prognosis of all the infarct locations due to its larger infarct size. It has a higher rate of total mortality (27 percent versus 11 percent), heart failure (41 percent versus 15 percent), and a lower ejection fraction on admission than an inferior myocardial infarction (38 percent versus 55 percent ).

The LAD artery supplies the majority of the interventricular septum, as well as the anterior, lateral, and apical walls of the left ventricle, as well as the majority of the right and left bundle branches and the bicuspid valve’s anterior papillary muscle (left ventricle).

The left or right ventricle’s end-diastolic volume (EDV) is the volume of blood in each chamber at the end of diastole before systole. Preload is synonymous with the EDV.

120 mL is a typical left ventricular EDV (range 65-240 mL). The EDV of the right ventricle in a typical range is (100-160 mL).

With an ejection fraction (EF) of less than 45 percent, the patient is most likely suffering from systolic dysfunction. Increases in right and left ventricular end-diastolic pressures and volumes are likely with a reduced EF because the ventricles are not adequately emptied. The left atrium and the pulmonary vasculature are affected by the increased pressures on the left side of the heart.

By causing an imbalance of the Starling forces acting across the capillaries, increased hydrostatic pressure in the pulmonary circulation favours the development of pulmonary oedema. With cardiogenic pulmonary oedema, capillary permeability is likely to remain unchanged.

Biventricular failure will result as a result of the pressure changes being transmitted to the right side of the circulation. The patient’s systemic vascular resistance is likely to be elevated as well, but it is not the most likely cause of his symptoms. The patient is suffering from cardiogenic shock as a result of biventricular failure. The patient has low cardiac output and is hypotensive. Right ventricular filling pressures are elevated, indicating right ventricular dysfunction.

Since the gas is less dense at higher altitudes, the density of a gas influences flows when passing through the orifice. Due to this reason, for a given flow rate, the bobbin will not be forced as far up the rotameter tube.

At higher altitudes, the volume of a fixed mass of gas increases, and therefore the molecules of gas are widely spaced resulting in a decrease in density with an increase in altitude.

Viscosity is simply termed as friction of gas. The viscosity of a gas is important only at low flow rates when the flow characteristic of the gas is laminar.

Charle’s law stated that the volume occupied by a fixed amount of gas is directly proportional to its absolute temperature (T) provided the pressure remains constant.

Boyle’s law for a fixed amount of gas at constant temperature, the pressure (P) and volume (V) are inversely proportional.

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

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

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

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

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

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

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

The 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.

Femoral nerve lesion (L2,L3 and L4) is characterised by weakness of the quadriceps femoris muscle. This results in weakness of extension of the knee, loss of sensation over the front of the thigh, and loss of the knee jerk reflex.

The skin over the lateral aspect of the thigh and knee, and the lower lateral quadrant of the buttock is supplied by the lateral cutaneous nerve of the thigh (L1,2).

The adductors of the hip are supplied by the obturator nerve (L2-4). This nerve also supplies sensation to the inner thigh.

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

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

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

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

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

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

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)

The drug of choice for the treatment of anaphylaxis is adrenaline. It has an intravenous route of administration. Since the patient already has intravenous access, the intramuscular route is not appropriate.

Second-line pharmacological intervention includes the use of chlorpheniramine 10mg intravenous, Hydrocortisone 200mg.

The adrenal (suprarenal) gland is composed of two main parts: the adrenal cortex, which is the largest and outer part of the gland, and the adrenal medulla. The adrenal cortex consists of three zones: 1. Zona glomerulosa (outermost layer) is responsible for the production of mineralocorticoids, mainly aldosterone, which regulates blood pressure and electrolyte balance. 2. Zona fasciculata (middle layer) is responsible for the production of glucocorticoids, predominantly cortisol, which increases blood sugar levels via gluconeogenesis, suppresses the immune system, and aids in metabolism. It also produces 11-deoxycorticosterone and corticosterone in addition to cortisol. 3. Zona reticularis (innermost layer) is responsible for the production of gonadocorticoids, mainly dehydroepiandrosterone (DHEA), which serves as the starting material for many other important hormones produced by the adrenal gland, such as oestrogen, progesterone, testosterone, and cortisol. It is also responsible for administering these hormones to the reproductive regions of the body.

The adrenal medulla majorly secretes epinephrine (adrenaline), and norepinephrine in small quantity. Both hormones have similar functions and initiate the flight or fight response.

Catecholamine is mediated by cholinergic nicotinic transmission through changes in sympathetic nervous system (T5 – T11), being increased during stress and hypoglycaemia.

Blood supply to the adrenal gland is by these three arteries: superior suprarenal arteries, middle suprarenal artery and inferior suprarenal artery. Venous drainage is via the suprarenal vein to the left renal vein or directly to the inferior vena cava on the right side. There is no portal (venous) system between cortex and medulla.

Pulse oximeters combine the principles of oximetry and plethysmography to noninvasively measure oxygen saturation in arterial blood. A sensor containing two or three light emitting diodes and a photodiode is placed across a perfused body part, commonly a finger, to be transilluminated. Oximetry depends on oxyhaemoglobin and deoxyhaemoglobin, and their ability to absorb the beams of light produced by the light emitting diodes: red light at 660 nm and infrared light at 960 nm.

The isosbestic point is the point wherein two different substances absorb light to the same extent. For oxyhaemoglobin and deoxyhaemoglobin, the points are at 590 nm and 805 nm. These are considered reference points where light absorption is independent of the degree of saturation.

Non-constant absorption of light is often due to the presence of an arterial pulsation, whilst constant absorption of light is seen in non-pulsatile tissues.

Most pulse oximeters are inaccurate at low SpO2, but is accurate at +/- 2% within the range of 70% to 100% SpO2. All pulse oximeters demonstrate a delay in between changes in SaO2 and SpO2, and display average readings every 10 to 20 seconds, hence they are unable to detect acute desaturation episodes.

Penicillinase is a narrow spectrum ?-lactamase that opens the ?-lactam ring and inactivates Penicillin G and some closely related congeners. The majority of Staphylococci and some strains of gonococci, B. subtilis, E. coli, and a few other bacteria produce penicillinase.

N. meningitidis is sensitive to penicillin and less than 20% resistance is found in pseudomonas.

Phase I and phase II metabolism are used by the liver to break down paracetamol.

1st Phase:

Prostaglandin synthetase and cytochrome P450 (CYP1A2, CYP2E2, CYP3A4 and CYP2D6) to N-acetyl-p-benzoquinoneimine (NAPQI) and N-acetylbenzo-semiquinoneimine. NAPQI is a toxic metabolite that binds to the sulfhydryl groups of cellular proteins in hepatocytes, making it toxic. This can result in centrilobular necrosis.

Glutathione and glutathione transferases prevent NAPQI from binding to hepatocytes at low paracetamol doses by preferentially binding to these toxic metabolites. The cysteine and mercapturic acid conjugates are then excreted in the urine. Depletion of glutathione occurs at higher doses of paracetamol, resulting in high levels of NAPQI and the risk of hepatocellular damage. Hepatotoxicity would not be an issue if the body’s glutathione stores were sufficient.

N-acetylcysteine is a precursor for glutathione synthesis and is the drug of choice for the treatment of paracetamol overdose.

Phase II:

Conjugation with glucuronic acid to paracetamol glucuronide is the most common method of metabolism and excretion, accounting for 60% of renally excreted metabolites. Paracetamol sulphate (35%), unchanged paracetamol (5%), and mercapturic acid are among the other renally excreted metabolites (3 percent ). The capacity of conjugation pathways is limited. The capacity of the sulphate conjugation pathway is lower than that of the glucuronidation pathway.

Because of the low pH in the stomach, paracetamol absorption is minimal (pKa value is 9.5). Paracetamol is absorbed quickly and completely in the alkaline environment of the small intestine. Oral bioavailability is extremely high, approaching 100%.

As a result, measuring paracetamol levels in plasma after an injury is important. Peak plasma concentrations are reached after 30-60 minutes, with a volume of distribution of 0.95 L/kg. It binds to plasma proteins at a rate of 10% to 25%.

The potency of local anaesthetics is directly proportional to lipid solubility because they need to penetrate the lipid-soluble membrane to enter the cell.

Protein binding has a direct relationship with the duration of action because the higher the ability of the drug to bind with membrane protein, the higher is the duration of action.

Higher the pKa of a drug, slower the onset of action. Because a drug with higher pKa will be more ionized than the one with lower pKa at a given pH. Local anaesthetics are weak bases, and unionized form diffuses more rapidly across the nerve membrane than the protonated form. As a result drugs with higher pKa will be more ionized will diffuse less across the nerve membrane.