With regards to compensatory response to blood loss, the following sequence of events take place:

1. Decrease in venous return, right atrial pressure and cardiac output
2. Baroreceptor reflexes (carotid sinus and aortic arch) are immediately activated
3. There is decreased afferent input to the cardiovascular centre in medulla. This inhibits parasympathetic reflexes and increases sympathetic response
4. This results in an increased cardiac output and increased SVR by direct sympathetic stimulation. There is increased circulating catecholamines and local tissue mediators (adenosine, potassium, NO2)
5. Fluid moves into the intravascular space as a result of decreased capillary hydrostatic pressure absorbing interstitial fluid.

A slower response is mounted by the hypothalamus-pituitary-adrenal axis.
6. Reduced renal blood flow is sensed by the intra renal baroreceptors and this stimulates release of renin by the juxta-glomerular apparatus.
7. There is cleavage of circulating Angiotensinogen to Angiotensin I, which is converted to Angiotensin II in the lungs (by Angiotensin Converting Enzyme ACE)

Angiotensin II is a powerful vasoconstrictor that sets off other endocrine pathways.
8. The adrenal cortex releases Aldosterone
9. There is antidiuretic hormone release from posterior pituitary (also in response to hypovolaemia being sensed by atrial stretch receptors)
10. This leads to sodium and water retention in the distal convoluted renal tubule to conserve fluid
Fluid conservation is also aided by an increased amount of cortisol which is secreted in response to the increase in circulating catecholamines and sympathetic stimulation.

Major surgery induces the systemic inflammatory response and this causes endothelial leakage and a low albumin level.

Albumin is a single polypeptide which is made but not stored in the liver. Therefore, levels are a reflection of synthetic activity. It is negatively charged and very soluble.

Only 40% of albumin is intravascular, and the rest in the in interstitial compartment.

If there was normal liver function during starvation, albumin will be maintained and proteolysis will occur elsewhere.
It is not catabolised during starvation.
Starvation and malnutrition may, however, present as part of other disease processes that are associated with hypalbuminaemia.

Causes of low albumin are

1. Decreased production (hepatic dysfunction)
2. Increased loss (renal dysfunction)
3. Redistribution (endothelial leak/damage)
4. Increased catabolism (very rare)

The following are some basic assumptions:

Extracellular fluid (ECF) makes up one-third of total body water (TBW), while intracellular fluid makes up the other two-thirds (ICF).
One-quarter of ECF is plasma, and three-quarters is interstitial fluid (ISF).
The volume receptors have a 7-10% blood volume change threshold. The osmoreceptors are sensitive to changes in osmolality of 1-2 percent.
Prior to the transfusion, the plasma osmolality is normal (between 287 and 290 mOsm/kg).
[Na+] in 0.9 percent N. saline is 154 mmol/L, which is similar to that of extracellular fluid. When given intravenously, this limits its distribution within the extracellular space, resulting in a plasma compartment:ISF volume ratio of 1:3.
In this time frame, one litre of 0.9 percent N. saline will increase plasma volume by about 250 mL, which could be the threshold for activation of the volume receptors in the atria, resulting in the release of atrial natriuretic peptide (ANP).

Because 0.9 percent N. saline is isosmotic, after a 1 L infusion, plasma osmolality will not change. No changes in antidiuretic hormone secretion will be detected by the hypothalamic osmoreceptors.

Because normal saline is protein-free, the oncotic pressure in the blood is slightly reduced after the saline infusion. As a result, fluid movement into the ISF is favoured (Starling’s hypothesis), and the lower oncotic pressure causes an immediate increase in the glomerular filtration rate (GFR) and a reduction in water reabsorption in the proximal tubule.

The flow of urine increases. There is no hormonal intermediary in this effect, so it is strictly local. Urine flow immediately increases. The fluid returns to the intravascular compartment, and urine flow continues until all of the transfused fluid has been excreted.

Blood pressure changes associated with a 1 L fluid infusion are unlikely to affect high-pressure baroreceptors in the carotid sinus.

The juxta-glomerular cells of the afferent arteriole are adjacent to the specialised cells (macula densa) of distal tubules. The sodium and chloride ions in the tubular fluid are detected by the macula densa. Renin release is inhibited when the tubular fluid contains too much sodium chloride. Hormonal changes take longer to manifest than physical changes that control glomerulotubular balance.
Hypertonic saline, not 0.9 percent N saline, is an osmotic diuretic.

Systemic vascular resistance (SVR) is a derived value based on:

SVR = (MAP-CVP)/CO x 80

= (60 -10)/5 x 80 = 800 dynes.s.cm-5

A correction factor of 80 is needed in converting mmHg to dynes.s.cm-5
Normal values is between 700 -1600 dynes.s.cm-5

Pulmonary resistance (PVR) = (MPAP-PCWP)/CO x 80

= (10 – 5)/5 x 80 = 80 dynes.s.cm-5

To account for body size, cardiac index (CI) can be used instead of CO. CI = CO/body surface area (m2) or mL/minute/m2.
N/B: either MAP and CVP, or MPAP and PCWP are used in calculation to get dynes.s.cm-5.

Porphyria is a group of disorders in which there is excess production and excess excretion of porphyrins and their precursors. They are usually genetic and are caused due to defects in the haem metabolic pathway. However, other factors like infection, pregnancy, mensuration, starvation may precipitate the attack.

Sulphonamides, barbiturates (methohexitone and thiopental), and phenytoin are considered to be precipitants so are not safe to use
Chloral hydrate is thought to be safe to use.
Etomidate lacks proper studies and may be used with caution but it is generally advised not to use this drug especially if other alternatives are available.

An ipsilateral phrenic nerve block will result from a successful interscalene block (ISB).

The phrenic nerve is the diaphragm’s sole motor supply, and ipsilateral hemidiaphragmatic paresis affects up to 100% of patients who receive ISBs. Phrenic nerve palsy is usually well tolerated and goes unnoticed by healthy people. However, forced vital capacity decreases by approximately 25%, which can produce ventilatory compromise in patients with limited pulmonary reserve, requiring assisted ventilation.

Vocal cord palsy occurs when the recurrent laryngeal nerve is inadvertently blocked, causing hoarseness and possibly acute respiratory insufficiency. Unless bilateral laryngeal nerve palsy occurs, which can cause severe laryngeal obstruction, this complication is usually of little consequence.

ISB can also cause cranial nerve X and XII palsy (Tapia’s syndrome). One-sided cord paralysis, aphonia, and the patient’s tongue deviating toward the block’s side are all symptoms.

When a local anaesthetic spreads to the stellate ganglion and its cervical sympathetic nerves, Horner’s syndrome can develop. Ptosis of the eyelid, miosis, and anhidrosis of the face are all symptoms. Horner’s syndrome, on the other hand, may not indicate that the brachial plexus is sufficiently blocked.

External carotid artery originates at the upper border of the thyroid cartilage. It ascends and lies anterior to the internal carotid arteries and posterior to the posterior belly of the digastric muscle and stylohyoid muscle.

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

Ventricular fibrillation (VT) is an arrhythmia caused by a distortion in the organized contraction of the ventricles leading to an inability to pump blood out into the body.

Amiodarone is an anti arrhythmic drug used for the treatment of ventricular and atrial fibrillations. It is the gold standard of treatment for refractory pulseless ventricular tachycardia (VT) and ventricular fibrillation (VF).

Guidelines for emergency treatment state that only the rescuer carrying out chest compressions on the patient may stand near the defibrillator as it charges.

Cardio-pulmonary resuscitation (CPR) during cardiac arrest is required for 2 minute cycles.

Hypovolaemia is as a cause of pulseless electrical activity (PEA) can be reversed using fluid resuscitation, whereas hypotension during cardiac arrest is either persistent or undetectable and is therefore irreversible.

Hyperkalaemia and hypocalcaemia are treated using calcium salts, but calcium chloride is often preferred over calcium gluconate.

During a pulseless VT or VF, a single precordial thump will be effective if administered within the first seconds of the occurrence of a shockable rhythm.

Damping is the reduction of energy in a system achieved by reducing the amplitude of oscillations. It is necessary to some degree to prevent wave overshoots.

Critical damping usually causes the system to be slow, so optimal damping is normally applied to provide a balance between speed and distortion.

Damping can cause errors if excessive (overdamping) or inadequate (Underdamping). The amount of damping in a system can be determined using the damping coefficient (D), where:

Undamped: 0
Critically damped: 1
Optimally damped: 0.64

An overdamped system will cause an artificial decrease in the systolic blood pressure, and an artificial increase in the diastolic blood pressure.

An underdamped system will cause an artificial increase in systolic blood pressure and an artificial decrease in diastolic blood pressure.

Damping can be caused by a number of factors affecting different parts of the system, including:

The tubing/cannula: The presence of air bubbles, increased blood viscosity or formation of blood clots.
The diaphragm/tubing: Increased malleability/compliance
The tubing: Presence of kinks, narrowing or too many ports of injection.

The answer here is a damped system will have a low systolic pressure, a high diastolic pressure with a normal mean pressure.

Pupil size is reduced by the pupillary light reflex and during accommodation for near vision. In the pupillary light reflex, light that strikes the retina is processed by retinal circuits that excite W-type retinal ganglion cells. These cells respond to diffuse illumination. The axons of some of the W-type cells project through the optic nerve and tract to the pretectal area, where they synapse in the olivary pretectal nucleus. This nucleus contains neurons that also respond to diffuse illumination. Activity of neurons of the olivary pretectal nucleus causes pupillary constriction by means of bilateral connections with parasympathetic preganglionic neurons in the Edinger-Westphal nuclei. The reflex results in contraction of the pupillary sphincter muscles in both eyes, even when light is shone into only one eye.

The right atrium receives blood supply from the SVC, IVC, and coronary sinus. It forms the right border of the heart.

The interior of the right atrium has 5 distinct features:
1. Sinus venarum – smooth, thin-walled posterior part of the right atrium where the SVC, IVC, and coronary sinus open
2. Musculi pectinati – an anterior rough, wall of pectinate muscles
3. Tricuspid valve orifice – the opening through which the right atrium empties blood into the right ventricle
4. Crista terminalis – separates the rough (musculi pectinati) from the smooth (sinus venarum) internally
5. Fossa ovalis – a thumbprint size depression in the interatrial septum which is a remnant of the oval foramen and its valve in the foetus

The trabeculae carneae are irregular muscular elevations that form the interior of the right ventricle.

There is minimum mixing of blood passing through the vessels.

The cerebral hemispheres are supplied by arteries that make up the Circle of Willis. The Circle of Willis is formed by the anastomosis of the two internal carotid arteries and two vertebral arteries. It lies in the subarachnoid space within the basal cisterns that surround the optic chiasma and infundibulum.

Each half of the circle is formed by:
1. Anterior communicating artery
2. Anterior cerebral artery
3. Internal carotid artery
4. Posterior communicating artery
5. Posterior cerebral arteries and the termination of the basilar artery

The circle and its branches supply; the corpus striatum, internal capsule, diencephalon, and midbrain.

The Weibull distribution are used to describe various types of observed failures of the components. it is used in reliability and survival analysis.

Regression Analysis is used to measure the relationship between among two or more variable. It determines the effect of independent variables on the dependent variables.

Student t-test is one of the most commonly used method to test the hypothesis. It determines the significant difference between the means of two different groups.

A time series is a collection of observations of well-defined data obtained at regular interval of time.

Kaplan-Meier estimator is used to estimate the survival function from lifetime data. It can be derived from maximum likelihood estimation of hazard function. It is most likely used to measure the fraction of patient’s life for a certain amount of time after treatment.

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

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

Fentanyl is a pethidine congener, 80€“100 times more potent than morphine, both in analgesia and respiratory depression. Fentanyl is ten times more potent than alfentanil.

Alfentanil has a more rapid onset than fentanyl even if fentanyl is more lipid-soluble because both are basic compounds and alfentanil has lower pKa, so a greater proportion of alfentanil is unionized and is more available to cross membranes.

Elimination of alfentanil is higher than fentanyl due to its lower volume of distribution.

Endotoxins are the lipopolysaccharides found in the outer cell wall of Gram-negative bacteria. They are responsible for providing the structure and stability of the cell wall.

They cannot be destroyed by normal sterilisation as they are heat stable molecules. They require the use of certain sterilant such as superoxide, peroxide and hypochlorite to be neutralised.

They stimulate strong immune responses, but can only be destroyed partially by specific antibodies. Repeat infections occur as memory T cells cannot be formed.

It can cause septicaemia and associated symptoms such as fever, shock, hypotension and nausea.

It activates the alternative complement pathway and the coagulation pathway using secreted cytokines.

It is not involved in botulism as clostridium botulinum, the responsible organism, secretes a neurotoxic exotoxin.

The guidelines for the management of cardiac arrest in hypothermic patients published by the UK Resuscitation Council differ slightly from the standard algorithm.

In a patient with a core temperature of less than 30°C, do the following:

If you’re on the shockable side of the algorithm (VF/VT), you should give three DC shocks.
Further shocks are not recommended until the patient has been rewarmed to a temperature of more than 30°C because the rhythm is refractory and unlikely to change.
There should be no drugs given because they will be ineffective.

In a patient with a core temperature of 30°C to 35°C, do the following:

DC shocks are used as usual.
Because they are metabolised much more slowly, the time between drug doses should be doubled.

Active rewarming and protection against hyperthermia should be given to the patient.

Option e is false because there is insufficient information to determine whether resuscitation should be stopped.

The blood alcohol concentration depends on:

-The rate of alcohol absorption from the gastrointestinal tract
-The volume of distribution of alcohol in the body, and
-The rate of elimination of alcohol from the body.

Total body water is approximately 50% in a female as compared to 60% in a typical male. This means that the volume of distribution of alcohol is lower in female compared with men. This is the principal reason for higher peak in alcohol levels.

About 4% of ingested alcohol is metabolised by the liver accounting for first pass metabolism and 0.4% is metabolised by gastric alcohol dehydrogenase (ADH). The absorbed alcohol is NOT distributed to fat cells but it is distributed throughout the water compartments (plasma, interstitial and intracellular) of the body. Women have very little gastric ADH, which further influences this exaggerated rise.

85-98% of the alcohol is oxidised by the liver to acetaldehyde and then to acetate. The metabolic pathway initially observes first order kinetics and then saturation or zero order kinetics leading to peaks in alcohol levels.

Clearance of ethanol per unit lean body mass is lower in male. The calculated alcohol elimination rate and liver volume per kilogram of lean body mass were 33% and 38% higher in women than in men, respectively.

Available evidence in the literature about the relationship of alcohol metabolism to the phases of the menstrual cycle is conflicting.

BMR is lower in females than males.

It decreases with increasing age.

There is an increase in BMR with increased muscle (i.e. lean tissue)

BMR is increased in stress and illness. There is also an catabolic state in these conditions.

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.

Rifampicin is a potent inducer of liver cytochrome enzymes. Other enzyme inducers are:
Carbamazepine
Sodium valproate
Phenytoin
Phenobarbitone

Risk ratio (relative risk) compares the probability of an event in an exposed (experimental) group to that of an event in the unexposed (control) group.

A relative risk of 1 suggests that there is no discernible difference in the outcome whether or not it has been exposed.

A relative risk of less than 1 indicates that probability of occurrence of an event is less if there is exposure.

A relative risk of greater than 1 highlights that an event is most likely to occur if it was provided exposure. Since you believe that exposure (the new drug) would have side effects, the value should be greater than 1.

Dinamap continuously measures the systolic, diastolic and mean arterial pressure along with pulse rate, thereby providing a continuous monitoring of the blood pressure using the osscillitonometric principle of measurement.

The device loses accuracy towards the extremes of BP and is more accurate with systolic compared with diastolic pressure. In arrhythmias such as AF, the devices are also inaccurate due to the major fluctuations associated with the individual pulse pressure variations.

The manual BP device is still the gold standard for BP measurement and monitoring.

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.

When the association among any two classes of object is defined by the presence of a third entity it is termed as indirect association. For an instance, the age of the employee may affect the rate of pay, which would have implications on job satisfaction. So, in this example, an indirect relationship between age and job satisfaction exists due to a third party i.e. rate of pay.

An intercostal nerve block is used for therapeutic and diagnostic purposes. Intercostal nerve blocks manage acute and chronic pain in the chest area. Common indications are chest wall surgery and shingles or postherpetic neuralgia.

An intercostal nerve block is also an effective option for the management of pain associated with chest trauma and rib fractures. These blocks have been shown to improve oxygenation and respiratory mechanics, and offer pain relief that is comparable to that of epidural analgesia.

This technique, however, is limited by the relatively large doses of local anaesthetic required, and relatively high intravascular uptake from the intercostal space, increasing risk of local anaesthetic toxicity.

For the local anaesthetic base to be stable in solution, it is formulated as a hydrochloride salt. As such, the molecules exist in a quaternary, water-soluble state at the time of injection. However, this form will not penetrate the neuron. The time for onset of local anaesthesia is therefore predicated on the proportion of molecules that convert to the tertiary, lipid-soluble structure when exposed to physiologic pH (7.4).

The ionization constant (pKa) for the anaesthetic predicts the proportion of molecules that exists in each of these states. By definition, the pKa of a molecule represents the pH at which 50% of the molecules exist in the lipid-soluble tertiary form and 50% in the quaternary, water-soluble form. The pKa of all local anaesthetics is >7.4 (physiologic pH), and therefore a greater proportion the molecules exists in the quaternary, water-soluble form when injected into tissue having normal pH of 7.4.

Furthermore, the acidic environment associated with inflamed tissues favours the quaternary, water-soluble configuration even further. Presumably, this accounts for difficulty when attempting to anesthetize inflamed or infected tissues; fewer molecules exist as tertiary lipid-soluble forms that can penetrate nerves.

Alpha 1 adrenergic receptor stimulation results in vasoconstriction of peripheral arteries mainly of those of skin, gut and kidney arterioles. This would cause and increase in total peripheral resistance and mean arterial pressure and as a result the perfusion of vital organs i.e. brain, heart and lungs are maintained.

Muscarinic M2 receptor also known as cholinergic receptor are located in heart, where they act to slow the heart rate down to normal sinus rhythm after negative stimulatory actions of parasympathetic nervous system. They also reduce contractile forces of the atrial cardiac muscle, and reduce conduction velocity of AV node. This could worsen the compensation.

Stimulation of beta 2 adrenergic receptor result in dilation of smooth muscle as in bronchodilation.

Beta 3 adrenergic receptors are present on cell surface f both white and brown adipocytes and are responsible for lipolysis, thermogenesis, and relaxation of intestinal smooth muscle.

Alpha 2 adrenergic receptor stimulation results in inhibition of the release of noradrenaline in a form of negative feedback.

Based on the laboratory reports, the patient is suffering from significant hyponatremia. The symptoms of hyponatremia are mainly neurological and depend on the severity and rapidity of onset of hyponatremia.

Patient symptom according to the hyponatremia level is correlated below:

125 – 130mmol/L – Nausea and malaise
115 – 125mmol/L – Headache, lethargy, seizures, and coma
<120mmol/L – Up to 11% present with coma.

Ampicillin belongs to the family of penicillin. Resistance to this group of drugs is due to β-lactamase production which opens the β-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.

Resistance to cephalosporins is due to changes in penicillin-binding proteins.

Resistance to macrolides are due to post-transcriptional methylation of 23s bacterial ribosomal RNA

Resistance to fluoroquinolones is due to mutations in DNA gyrase.