Doxycycline belongs to the family of tetracyclines and inhibits protein synthesis through reversible binding to bacterial 30s ribosomal subunits, which prevent binding of new incoming amino acids (aminoacyl-tRNA) and thus interfere with peptide growth.

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.

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.

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 cardiac muscle’s contractile fibres have a much more stable resting potential than its conductive fibres. In the ventricular fibres it is -90mV and in the atrial fibres it is -80mV.

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. (QRS complex)

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 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

Staphylococcus aureus infection is the most likely cause.

Surgical site infections (SSI) occur when there is a breach in tissue surfaces and allow normal commensals and other pathogens to initiate infection. They are a major cause of morbidity and mortality.

SSI comprise up to 20% of healthcare associated infections and approximately 5% of patients undergoing surgery will develop an SSI as a result.
The organisms are usually derived from the patient’s own body.

Measures that may increase the risk of SSI include:
-Shaving the wound using a single use electrical razor with a disposable head
-Using a non iodine impregnated surgical drape if one is needed
-Tissue hypoxia
-Delayed prophylactic antibiotics administration in tourniquet surgery, patients with a prosthesis or valve, in clean-contaminated surgery of in contaminated surgery.

Measures that may decrease the risk of SSI include:
1. Intraoperatively
– Prepare the skin with alcoholic chlorhexidine (Lowest incidence of SSI)
-Cover surgical site with dressing

In contrast to previous individual RCT’s, a recent meta analysis has confirmed that administration of supplementary oxygen does not reduce the risk of wound infection and wound edge protectors do not appear to confer benefit.

2. Post operatively
Tissue viability advice for management of surgical wounds healing by secondary intention

Use of diathermy for skin incisions
In the NICE guidelines the use of diathermy for skin incisions is not advocated. Several randomised controlled trials have been undertaken and demonstrated no increase in risk of SSI when diathermy is used.

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 clinical picture best describes a probable drug interaction with pethidine.

Phenelzine, a monoamine oxidase (MAO) inhibitor, when given with pethidine, an opioid analgesic, may lead to episodes of hypertension, rigidity, excitation, hyperpyrexia, seizures, coma and death. Studies have shown that pethidine reacts more significantly with MAO inhibitors than morphine.

When pethidine is metabolised to normeperidine, it acts as a serotonin reuptake inhibitor and cause an increase in serotonin levels in the brain. MAO inhibitors can also lead to elevated levels of serotonin because of its mechanism of action by inhibiting the enzyme monoamine oxidase that degrades serotonin.

The excess serotonin levels may lead to serotonin syndrome, of which some of the common precipitating drugs are selective serotonin reuptake inhibitors, MAO inhibitors, tricyclic antidepressants, meperidine, and St. John’s Wort. Onset of symptoms is within hours, which includes fever, agitation, tremor, clonus, hyperreflexia and diaphoresis.

Drug interaction between phenelzine and paracetamol do not commonly precipitate serotonin syndrome.

Neuroleptic malignant syndrome is due to dopamine antagonism, precipitated commonly by antipsychotics. Its onset of symptoms occur in 1 to 3 days, and is characterized by fever, encephalopathy, unstable vitals signs, elevated CPK, and rigidity.

Altered mental status is the most common manifestation of sepsis-associated encephalopathy. Patient also exhibit confusional states and inappropriate behaviour. In some cases, this may lead to coma and death.

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

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

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

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

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

Patients who have sustained thermal injuries are at high risk of becoming hypercatabolic with larger cardiac outputs and oxygen consumptions.

The hypermetabolic states increase with an increase in the burn severity and surface area of the skin affected. A patient with thermal injuries affecting 60% of the total surface area of the body will have twice the normal metabolic rate.

The optimal temperature for nursing patients with burn injuries is 30°C to conserve the energy usage. The areas affected by the burn injuries should be covered to reduce loss of fluid via evaporation. Resetting hypothalamic thermoregulation will cause a 1-2°C increase in core temperature.

Burn injuries will have an immediate effect on the intestine, destroying the barrier function and allowing for the movement of bacteria and endotoxins within hours.

Enteral nutrition allows for the delivery of nutrients directly to the stomach or intestine. It has correlation with a dampened hypermetabolic response to a thermal and injury, especially when initiated early as it helps to protect the integrity of the mucosal lining and prevents the movement of bacteria into circulation.

Diet changes have been linked to reduced mortality due to burn injuries. Diets high in protein especially (calorie: nitrogen ratio of 100: 1), have the highest correlation with improved survival rates.

Parenteral feeds may be required alongside enteral nutrition, even with the increased risks of infection.

An elevated arterial blood lactate level and an increase anion gap ([Na + K] – [Cl + HCO3]) of >20mmol gives rise to lactic acidosis. It can also be a result of overproduction and/or reduced metabolism of lactic acid.

The liver and kidney are the main sites of lactate metabolism, not skeletal muscle.

The two types of lactic acidosis that are known are:

Type A – due to tissue hypoxia, inadequate tissue perfusion and anaerobic glycolysis. These may be seen in cardiac arrest, shock, hypoxaemia and anaemia. The management of type A lactic acidosis involves reversing the underlying cause of the tissue hypoxia.

Type B – occurs in the absence of tissue hypoxia. Some of the causes of this include hepatic failure, renal failure, diabetes mellitus, pancreatitis and infection. Some drugs can also cause this lie aspirin, ethanol, methanol, biguanides and intravenous fructose.

The mainstay of treatment involves:
1. Optimising tissue oxygen delivery
2. Correcting the cause
3. Intravenous sodium bicarbonate

In resistant cases, peritoneal dialysis can be performed.

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.

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.

Oxygen delivery depends on 2 variables.
1) Content of oxygen in blood
2) Cardiac output

Oxygen content (arterial) = (Hb (g/dL) x 1.39 x SaO2 (%) ) + (0.023 x PaO2 (kPa))

Oxygen content (mixed venous) = (Hb (g/dL) x 1.39 x mixed venous saturation) + (0.023 x mixed venous partial pressure of oxygen in kPA)

Huffner’s constant = 1.39 = 1g of Hb binds to 1.39 ml of O2

Oxygen delivery DO2 (ml/min) = 10 x Cardiac output (L/min) x Oxygen content
Normally 1000ml/min

Oxygen consumption VO2 (ml/min) = 10 x Cardiac output (L/min) x Difference in arterial and mixed venous oxygen content
Normally 250 ml/min

Oxygen extraction ratio (OER) = VO2/DO2
Normally approximately 25%

The usual method of calculating the dose of a drug to be given to patients of normal weight is to use total body weight (TBW). This is because the lean body weight (LBW) and ideal body weight (IBW) dosing scalars are similar in these patients.

Because the LBW and fat mass do not increase in proportion in patients with morbid obesity, this is not the case. Drugs that are lipid soluble, such as propofol or thiopentone, can cause a relative overdose. Lean body mass is a better scalar in these situations.

Suxamethonium has a small volume of distribution, so the dose is best calculated using the TBW to ensure optimal and deep intubating conditions. The higher dose was justified because these patients’ plasma cholinesterase activity was elevated.

Other scalars include:

The dose of highly lipid soluble drugs like benzodiazepines, thiopentone, and propofol can be calculated using lean body weight (LBW). The formula LBW = IBW + 20% can be used on occasion.

Fentanyl, rocuronium, atracurium, vecuronium, morphine, paracetamol, bupivacaine, and lidocaine are all administered with LBW.

Formulas can be used to calculate the ideal body weight (IBW). There are a number of drawbacks, including the fact that patients of the same height receive the same dose, and the formulae do not account for changes in body composition associated with obesity. Because IBW is typically lower than LBW, administering a drug based on IBW may result in underdosing. The body mass index (BMI) isn’t used to calculate drug dosage directly.

The international system of units, or system international d’unites (SI) is a collection of measurements derived from expanding the metric system.

There are seven base units, which are:

Metre (m): a unit of length
Second (s): a unit of time
Kilogram (kg): a unit of mass
Ampere (A): a unit of electrical current
Kelvin (K): a unit of thermodynamic temperature
Candela (cd): a unit of luminous intensity
Mole (mol): a unit of substance.

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

A passive leg raise can lead to transient increases in blood pressure and stroke volume as it increased the amount of venous return to the heart. Venous return increases in this situation as it transfers a larger volume of blood from the lower limbs to the right heart. It therefore mimics a fluid challenge. However its effects are short lasting and often lead to minimal increases in blood pressure. It therefore should not be used to treat shock in isolation. The passive leg raise is useful in determining the likelihood that a patient with shock will respond to fluid resuscitation.

Stroke volume (via a cardiac monitor) and/or pulse pressure (via an arterial line) should be measured to assess the effects of a passive leg raise. An increase in stroke volume by 9% or in pulse pressure by 10% are considered indicative of fluid responsiveness.

Blood that enters the ventricles during diastole causes stretching of sarcomeres within cardiac muscle. The extent to which they stretch is proportional to the strength of ventricular muscle contraction. Therefore, the venous return (amount of blood returned to the heart) is proportional to stroke volume. The end diastolic volume is determined by venous return and is also proportional to stroke volume.

Cardiac muscle contraction strength is dependent on the action of adrenaline and noradrenaline, but these hormones contribute to cardiac contractility, not to stroke volume.

Hydrochloric acid is lost when you vomit for a long time (HCl). As a result, the following can be expected, in varying degrees of severity:

Hypokalaemia
Hypochloraemia
Increased bicarbonate to compensate for chloride loss and metabolic alkalosis

The alkalosis causes potassium to move from the intracellular to the extracellular compartment at first. Long-term vomiting and dehydration cause potassium to be excreted by the kidneys in order to conserve sodium. Dehydration can cause urea and creatinine levels to rise.

The actual base excess is always greater than the standard base excess.

The actual base excess (BE) is a measurement of a base’s contribution to a blood gas picture’s metabolic component. It’s the amount of base that needs to be added to a blood sample to bring the pH back to 7.4 after the respiratory component of a blood gas picture has been corrected (PaCO2 of 40 mmHg or 5.3 kPa). The BE has a normal range of +2 to 2. A large positive BE indicates a severe metabolic alkalosis, while a large negative BE indicates a severe metabolic acidosis. As a result, the actual BE in vitro is unaffected by CO2.

In vivo, however, standard BE is not independent of pCO2 because blood with haemoglobin acts as a better buffer than total ECF.

As a result, it is impossible to tell the difference between compensating for a respiratory disorder and compensating for the presence of a primary metabolic disorder.

The differences between in vitro and in vivo behaviour can be mostly eliminated if the BE is calculated for a haemoglobin concentration of 50 g/L (the ‘effective’ or virtual value of Hb if it was distributed throughout the extracellular space) rather than the actual haemoglobin. Because haemoglobin has a lower buffering capacity, the standard BE is higher than the actual BE. It reflects the BE better in the extracellular space rather than just the intravascular compartment.

The electrical conduction system of the heart starts with the SA node which generates spontaneous action potentials.

This is conducted across both atria by cell to cell conduction, and occurs at around 1 m/s. The only pathway for the action potential to enter the ventricles is through the AV node in a normal heart.
At this site, conduction is very slow at 0.05ms, which allows for the atria to completely contract and fill the ventricles with blood before the ventricles depolarise and contract.

The action potentials are conducted through the Bundle of His from the AV node which then splits into the left and right bundle branches. This conduction is very fast, (,2m/s), and brings the action potential to the Purkinje fibres.

Purkinje fibres are specialised conducting cells which allow for a faster conduction speed of the action potential (,2-4m/s). This allows for a strong synchronized contraction from the ventricle and thus efficient generation of pressure in systole.

Atypical antipsychotic drugs include risperidone and quetiapine. They not only inhibit dopamine receptors in the limbic system, but also histamine (H1) and alpha2 adrenoreceptors. When combined with general and/or central neuraxial block, this might result in severe hypotension.

Donepezil (Aricept) is an acetylcholinesterase (AChE) inhibitor that increases the neurotransmitter acetylcholine in the cerebral cortex and hippocampus in a reversible, non-competitive manner. It is used to reduce the advancement of Alzheimer’s disease symptoms (AD). Rivastigmine and galantamine are two more drugs that work in the same way.

Ginkgo Biloba contains anti-oxidant characteristics and is used to treat early-stage Alzheimer’s disease, vascular dementia, and peripheral vascular disease. It lowers platelet adhesiveness and decreases platelet activating factor (PAF) increasing the risk f bleeding, especially in individuals who are also taking anticoagulants and antiplatelet medication.

Memantine is an antagonist of the NMDA receptor. Synaptic plasticity, which is thought to be a critical component of learning and memory, can be inhibited at high doses. The use of ketamine is a relative contraindication since antagonism of this receptor can cause a dissociative state.

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.

Loop diuretics act by causing inhibition of Na+ K+ 2Cl– symporter present at the luminal membrane of the ascending limb of the loop of Henle.

Furosemide, torsemide, bumetanide, ethacrynic acid, furosemide, piretanide, tripamide, and mersalyl are the important members of this group

The main use of loop diuretics is to remove the oedema fluid in renal, hepatic, or cardiac diseases. Thus they are useful in the treatment of acute heart failure. These can be administered i.v. for prompt relief of acute pulmonary oedema (due to vasodilatory action).

Hypokalaemia, hypomagnesemia, hyponatremia, alkalosis, hyperglycaemia, hyperuricemia, and dyslipidaemia are seen with both thiazides as well as loop diuretics

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.

Myasthenic and cholinergic crises are two crises which are similar in their clinical presentation.

Myasthenic crisis can be caused by:
-lack of acetylcholine,
-poor compliance with medication,
-infection

Cholinergic crisis can be caused by excess cholinesterase inhibitor medication (mimicking organophosphate poisoning) causing excess acetylcholine.

Differentiation between the 2 crises is made by giving incremental doses of the short acting cholinesterase inhibitor, Edrophonium.
This increase acetylcholine levels and will make a myasthenic crisis better and a cholinergic crisis worse.

The deep inguinal ring is the entrance of the inguinal canal. It is an opening in the transversalis fascia around 1 cm above the inguinal ligament. Therefore, the superolateral wall is made by the transervalis fascia.

The inferior epigastric vessels run medially to the deep inguinal ring forming its inferomedial border.

The inguinal canal extends obliquely from the deep inguinal ring to the superficial inguinal ring.
An indirect inguinal hernia arises through the deep inguinal ring lateral to the inferior epigastric vessels.

The patient is rebreathing carbon dioxide that has been exhaled.

Exhaustion of the soda lime and failure of the expiratory valve are the two most likely causes. A leak in the inspiratory limb is a less likely cause. Increased inhaled and exhaled carbon dioxide levels may appear with a normal-looking capnogram if the expiratory valve is ineffective.

The patient will exhale into both the inspiratory and expiratory limbs if the inspiratory valve is inoperable. A slanted downstroke inspiratory phase (as the patient inhales carbon dioxide-containing gas from the inspiratory limb) and increased end-tidal carbon dioxide can be seen on the capnogram.

Even if the soda lime were exhausted, a high fresh gas flow would be enough to prevent rebreathing. The difference in oxygen concentrations in inspired and expired breaths would be less pronounced.

Hypercapnia is caused by respiratory obstruction and malignant hyperthermia, but not by rebreathing.

Sixty-seven percent of filtered water is reabsorbed in the proximal tubule. The driving force for water reabsorption is a transtubular osmotic gradient established by reabsorption of solutes (e.g., NaCl, Na+-glucose).

Henle’s loop reabsorbs approximately 25% of filtered NaCl and 15% of filtered water. The thin ascending limb reabsorbs NaCl by a passive mechanism, and is impermeable to water. Reabsorption of water, but not NaCl, in the descending thin limb increases the concentration of NaCl in the tubule fluid entering the ascending thin limb. As the NaCl-rich fluid moves toward the cortex, NaCl diffuses out of the tubule lumen across the ascending thin limb and into the medullary interstitial fluid, down a concentration gradient as directed from the tubule fluid to the interstitium. This mechanism is known as the counter current multiplier.

The distal tubule and collecting duct reabsorb approximately 8% of filtered NaCl, secrete variable amounts of K+ and H+, and reabsorb a variable amount of water (approximately 8%-17%).

A compound that contains an asymmetric centre (chiral atom or chiral centre) and thus can occur in two non-superimposable mirror-image forms (enantiomers) are called chiral compounds.

Desflurane, Halothane, and isoflurane are chiral compounds but Sevoflurane is not a chiral compound.