Insulin is secreted from the ? cells of the pancreas. It consists of 51 amino acids arranged in two chains. It interacts with cell surface receptors (not the nuclear receptors and thus mechanism of action is not similar to steroids).
Since insulin can pass from plasma to interstitium and lymphatics, it can be measured in lymph but the concentrations here can be up to 30% less than that of plasma.

It decreases blood glucose by stimulating the entry of glucose in muscle and fat (by increasing the synthesis of Glucose transporters)

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= (165/1050)-(132/1044)

ARR= (0.157-0.126)

ARR= 0.031

NNT= 1/0.031

NNT=32.3

Tonic-clonic (Grand mal) epilepsy is characterised by a general loss of consciousness with violent involuntary muscle contractions.

The NICE guidelines for treatment indicates the use of sodium valproate and lamotrigine, but sodium valproate unsuitable in this case and she is a woman of reproductive age and it is known to have teratogenic effects. Lamotrigine is a more suitable choice, prescribed as 800mg daily.

NICE guidelines also advice an additional prescription of 5mg of folic acid daily for women on anticonvulsant therapy looking to get pregnant. It also warns of the need for extra contraceptive precaution as there is a possibly that the anticonvulsant agent can reduce levels of contraceptive agents.

Stimulation of the vagal nerve stimulation is only necessary in patients who are refractory to medical treatment and not candidates for surgical resection.

The first line of treatment in case of hypotension is fluid resuscitation.

Activated charcoal can be used within one hour of tricyclic antidepressant ingestion but an intact and secure airway must be checked before intervention. The risk of aspiration should be assessed.

Vasopressors are indicated for the treatment of hypotension following (Tricyclic Antidepressant) TCA overdose when patients fail to respond to fluids and bicarbonate.

The Kappa Statistic or Cohen’s Kappa is a statistical measure of inter-rater reliability for categorical variables. It is used when two raters both apply a criterion based on a tool to assess whether or not some condition occur. A good example can be two doctors rating individuals for diabetes occurrence on the basis of symptoms.

It gives a quantitative measure of the magnitude of agreement between observers.

Kappa can take any value between 0 and 1. 0 implies the observers are in complete disagreement and a value of 1 implies complete agreement.

Foramen ovale, ductus arteriosus (DA) and ductus venosus (DV) are the three important cardiac shunts in-utero.

At birth the umbilical vessels constrict in response to stretch as they are clamped. Blood flow through the ductus venosus (DV) decreases but the DV closes passively in 3-10 days.

As the pulmonary circulation is established, there is a drastic fall in pulmonary vascular resistance and an increased pulmonary blood flow. This increases flow and pressure in the Left Atrium that exceeds that of the right atrium. The difference in pressure usually leads to the IMMEDIATE closure of the foramen ovale.

The DA is functionally closed within the first 36-hours of birth in a healthy full-term newborn. Subsequent endothelial and fibroblast proliferation leads to permanent anatomical closure within 2 – 3 weeks.

Oxygenated blood from the placenta passes via the umbilical vein to the liver. Blood also bypasses the liver via the ductus venosus into the inferior vena cava (IVC). The Crista dividens is a tissue flap situated at the junction of the IVC and the right atrium (RA). This flap directs the oxygen-rich blood, along the posterior aspect of the IVC, through the foramen ovale into the left atrium (LA).

The Eustachian valve also known as the valve of The IVC is a remnant of the crista dividens.

For establishing a cause effect relationship, following criteria must be met:

1. Coherence & Consistency

2. Temporal Precedence

3. Specificity

As can be seen, sensitivity (The probability of a positive test) is not among these deciding factors..

Warfarin prevents reductive metabolism of the inactive vitamin K epoxide back to its active hydroquinone form. Thus, warfarin inhibits the synthesis of vitamin K dependent clotting factors: X, IX, VII, II (prothrombin), and of the anticoagulants protein C and protein S. The therapeutic range for oral anticoagulant therapy is defined in terms of an international normalized ratio (INR). The INR is the prothrombin time ratio (patient prothrombin time/mean of normal prothrombin time for lab)ISI, where the ISI exponent refers to the International Sensitivity Index and is dependent on the specific reagents and instruments used for the determination. A prolonged INR is widely used as an indication of integrity of the coagulation system in liver disease and other disorders, it has been validated only in patients in steady state on chronic warfarin therapy.

Prothrombin complex concentrate (PCC) is used to replace congenital or acquired vitamin-K deficiency warfarin-induced anticoagulant effect, particularly in the emergent setting.

Intravenous vitamin K has a slower onset of action compared to PCC, but is useful for long term therapy.

Fresh frozen plasma (FFP) prepared from freshly donated blood is the usual source of the vitamin K-dependent factors and is the only source of factor V. The factors needed, however, are found in small quantities compared to PCC.

Cryoprecipitate is indicated for hypofibrinogenemia/dysfibrinogenemia, von Willebrand disease, haemophilia A, factor XIII deficiency, and management of bleeding related to thrombolytic therapy.

Laminar flow can be defined as the motion of a fluid where every particle in the fluid follows the same path of its previous particles. The following are properties of laminar flow of gas or fluids:

1. Smooth unobstructed flow of gas through a tube of relatively uniform diameter
2. Few directional changes
3. Slow, steady flow through straight smooth, rigid, large calibre, cylindrical tube
4. Outer layer flow slower than the centre due to friction, results in discrete cylindrical layers, or streamlines
5. Double flow by doubling pressure as long as the flow pattern remains laminar

Poiseuille’s Law relates the factors that determine laminar flow. It indicates the degree of resistance to fluid flow through a tube. The resistance to fluid flow through a tube is directly related to the length, flow and viscosity; and inversely related to the radius of the tube to the fourth power. This means that, when the radius is doubled, there is increase in flow by a factor of 16.

The basilic vein is one of the primary veins that drain the upper limb, like the cephalic vein. It begins as the dorsal venous arch. The basilic vein originates from the ulnar side of the dorsal arch of the upper limb passes along the posteromedial aspect of the forearm, moving towards the anterior surface of the elbow.

The basilic vein pierces the deep fascia at the elbow and joins the venae commitantes of the brachial vein to form the axillary vein.

The basilic vein passes deep under the muscles as it moves midway up the humerus. At the lower border of the teres major muscle, the anterior and posterior circumflex humeral veins feed into it.

Adrenaline is released by the adrenal glands, acts on ? 1 and 2, ? 1 and 2 receptors, and is responsible for fight or flight response.

It acts on ? 2 receptors in skeletal muscle vessels-causing vasodilation.

It acts on ? adrenergic receptors to inhibit insulin secretion by the pancreas. It also stimulates glycogenolysis in the liver and muscle, stimulates glycolysis in muscle.

It acts on ? adrenergic receptors to stimulate glucagon secretion in the pancreas
It also stimulates Adrenocorticotrophic Hormone (ACTH) and stimulates lipolysis by adipose tissue

Funnel plot is essentially a scatterplot of the effect of treatment against a particular measure of study precision. Its primal purpose is to serve as a visual aid and help in detection of bias or systematic heterogenity.

Mixed venous oxygen content (CvO2) is the oxygen concentration in 100mL of mixed venous blood taken from the pulmonary artery. It is usually 12-17 mL/dL (70-75%). It is represented mathematically as:

CvO2 = (1.34 x Hgb x SvO2 x 0.01) + (0.003 x PvO2)

Where,

1.34 = Huffner’s constant
Hgb = Haemoglobin level (g/dL)
SvO2 = % oxyhaemoglobin saturation of mixed venous blood
PvO2 = 0.0225 = mL of O2 dissolved per 100mL plasma per kPa, or 0.003 mL per mmHg

Therefore,

CvO2 = (1.34 x 10 x 70 x 0.01) + (0.003 x 50)

CvO2 = 9.38 + 0.15 = 9.53 mL/100mL

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)

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.

The blood brain barrier (BBB) consists of the ultrafiltration barrier in the choroid plexus and the barrier around cerebral capillaries. The barrier is made by endothelial cells which line the interior of all blood vessels. In the capillaries that form the blood–brain barrier, endothelial cells are wedged extremely close to each other, forming so-called tight junctions.

Outside of the BBB lies the hypothalamus, third and fourth ventricles and the chemoreceptor trigger zone (CTZ).

Water, oxygen and carbon dioxide cross the BBB freely but glucose is controlled. The ability of chemicals to cross the barrier is proportional to their lipid solubility, not their water solubility. It’s ability to cross is inversely proportional to their molecular size and charge.

In neonates, the BBB is less effective than in adults. This is why there is increased passage of opioids and bile salts (kernicterus) into the neonatal brain.

In meningitis, the effectiveness and permeability of the BBB is affected, and as a result, this effect helps the passage of antibiotics which would otherwise not normally be able to cross.

Two bonded wires of dissimilar metals, iron/constantan or copper/constantan, make up a thermocouple (constantan is an alloy of copper and nickel). At the tip, a thermojunction voltage is generated that is proportional to temperature (Seebeck effect).

All of the other connections are non-linear.

For a single compartment model, the relationship between a decrease in plasma concentration of an intravenous bolus of a drug and time is a washout exponential.

A sine wave is the relationship between current and degrees or time from a mains power source.

A sigmoid curve represents the relationship between efficacy and log-dose of a pure agonist on mu receptors.

The pressure of a fixed mass of gas and its volume (Boyle’s law) at a fixed temperature are inversely proportional, resulting in a hyperbolic curve.

In general practice, majority of phase 3 trials and some of the trials conducted in phase 2 are randomized. Because phase 4 trials require a huge sample size, they are not randomized as much. The primal reason behind conducting phase 3 trials is to test the efficiency and safety in a significant sample population. At this point it is assumed that the drug is effective up to a certain extent.

During a case-control study, subjects that exhibit outcomes of interest are compared with those who don’t show the expected outcome. The extent of exposure to a particular risk factor is then matched between cases and controls. If the exposure among cases surpasses controls, it becomes a risk factor for the outcome that is being studied.

Pilot studies are conducted on a lower and much smaller level, to assess if a randomized controlled trial of the crucial components of a study will be plausible.

Phase 4 trials are the ones that are conducted after its established that the drug is effective and is approved by the regulating authority for use. These trials are concerned with the side effects and potential risks associated with the long term usage of the drug.

The bifurcation of the abdominal aorta into common iliac arteries occurs at the level of L4. The bifurcation is a common site for atherosclerotic plaques as it is an area of high turbulence.

Leriche Syndrome is an aortoiliac occlusive disease and affects the distal abdominal aorta, iliac arteries, and femoropopliteal vessels. It has a triad of symptoms:
1. Claudication (cramping lower extremities pain that is reproducible by exercise)
2. Impotence (reduced penile arterial flow)
3. Absent/weak femoral pulses (hallmark)

T12 – aorta enters the diaphragm with the thoracic duct and azygous veins

L2 – testicular or ovarian arteries branch off the aorta

L3 – inferior mesenteric artery

The arterial blood gas analysis indicates presence of acute respiratory acidosis.

Central chemoreceptors are located in the ventral medulla and respond directly to presence of hydrogen ions in the CSF. When stimulated, it causes an increase in respiratory rate.

It is believed that hydrogen ions may be the only important direct stimulus for these neurons, however, CO2 is believed to stimulate these neurons secondarily by changing the hydrogen ion concentration.

Changes in O2 concentration have virtually no direct effect on the respiratory centre itself to alter respiratory drive. Although, O2 changes do have an indirect effect by acting through the peripheral chemoreceptors.

The adrenal medulla comprises chromaffin cells (pheochromocytes), which are functionally equivalent to postganglionic sympathetic neurons. They synthesize, store and release the catecholamines noradrenaline (norepinephrine) and adrenaline (epinephrine) into the venous sinusoids.
The majority of the chromaffin cells synthesize adrenaline.

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.

Observation bias occurs when the behaviour of an individual changes that results from their awareness of being observed.

Recall bias introduced when participants in a study are systematically more or less likely to recall and relate information on exposure depending on their outcome status.

Attrition bias is a systematic error caused by unequal loss of participants from a randomized controlled trial (RCT). In clinical trials, participants might dropout due to unsatisfactory treatment or efficacy, intolerable adverse events, or even death.

Selection bias introduced when the individuals are not chosen randomly to take a part in the study. It usually occurs when the research decides who is going to be studied, they are not the representative of the population.

Lead-time bias occurs when a disease is detected by a screening test at an earlier time point rather than it would have been diagnosed by its clinical appearance. In this bias, earlier detection improves the survival time in the intervention group.

Mivacurium, when administered at doses greater than 0.2 mg/kg,increases the risk for hypotension, tachycardia, and erythema. This is due to the ability of mivacurium to release histamine with increasing dose. Contrary to this fact, anaphylaxis is rare for mivacurium because of the short duration of histamine release.

The effective dose 50 (ED50) of mivacurium is between 0.08-0.15 mg/kg. It is administered slowly to prevent and decrease the risk of developing adverse effects.

Mivacurium has a high potency thus a longer duration of action, however this is not the answer that we are looking for.

Although drug metabolism takes longer for mivacurium than succinylcholine, it has no effect on the dose required for intubation.

Oxygen consumption (VO2) refers to the optimal amount of oxygen used by the body during exercise.

It is calculated mathematically by:

VO2 = 3.5 x 50 x 8 = 1400 mL/kg/minute

where,

1 MET = 3.5 mL O2/kg/minute is utilized by the body.

Note:

1 MET Eating
Dressing
Use toilet
Walking slowly on level ground at 2-3 mph
2 METs Playing a musical instrument
Walking indoors around house
Light housework
4 METs Climbing a flight of stairs
Walking up hill
Running a short distance
Heavy housework, scrubbing floors, moving heavy furniture
Walking on level ground at 4 mph
Recreational activity, e.g. golf, bowling, dancing, tennis
6 METs Leisurely swimming
Leisurely cycling along the flat (8-10 mph)
8 METs Cycling along the flat (10-14 mph)
Basketball game
10 METs Moderate to hard swimming
Competitive football
Fast cycling (14-16 mph)

The abdominal arteries are divided into 3 branches;
– 3 main unpaired trunks (celiac trunk, superior mesenteric, inferior mesenteric arteries)
– 6 paired branches
– unpaired median sacral artery.

We can group the abdominal aorta as follows;
-Ventral which includes: Coeliac trunk, superior mesenteric and inferior mesenteric arteries
-Lateral: Inferior phrenic, middle suprarenal, renal and gonadal arteries
-Dorsal: Lumbar and median sacral arteries
-Terminal : Right and left common iliac arteries

The celiac trunk (L1) takes blood the foregut and its found posterior to the stomach. The unpaired superior mesenteric artery supplies blood to the mid-gut.

The paired renal arteries form the inferior suprarenal arteries. The renal arteries arise around L1/L2 and takes blood to either side of the kidneys.

The median sacral artery supplies blood to the lumbar vertebrae the L4 and L5.

The renal arteries branch from the abdominal aorta just below the origin of the superior mesenteric artery. The right renal artery is higher and longer than the left renal artery. The left renal artery passes behind the left renal vein, the body of the pancreas, and the splenic vein.

The important landmarks of vessels arising from the abdominal aorta at different levels of vertebrae are:

T10 – oesophageal opening in the diaphragm

T12 – Coeliac trunk, aortic hiatus in the diaphragm

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

The neuromuscular blocking agent is likely to be filtered and not reabsorbed by the renal tubules due to an exclusion process.

Neuromuscular blocking agents that contain one or more quaternary nitrogen atoms are polar and ionised. As a result, the molecules have low lipid solubility, low membrane diffusion capacity, and low distribution volume.

It’s unlikely that a compound with three quaternary nitrogen atoms is an ester. Its high polarity would prevent molecules from moving quickly into tissues.

When drugs have a low hepatic extraction ratio (0.3), the venous and arterial drug concentrations are nearly identical. The liver is not the primary site of drug metabolism.

Therefore:

Changes in liver blood flow have no effect on clearance.
Protein binding, intrinsic metabolism, and excretion are all very sensitive to changes in clearance.
When taken orally, there is no first-pass metabolism.

There is no reason for the lungs to eliminate any neuromuscular blocking agent.

Second messengers relay signals to target molecules in the cytoplasm or nucleus when an agonist interacts with a receptor on the cell surface. They also amplify the strength of the signal. The most ubiquitous and abundant second messenger is calcium and it regulates multiple cellular functions in the body.

These include:
Muscle contraction (skeletal, smooth and cardiac)
Exocytosis (neurotransmitter release at synapses and insulin secretion)
Apoptosis
Cell adhesion to the extracellular matrix
Lymphocyte activation
Biochemical changes mediated by protein kinase C.

cAMP is either inhibited or stimulated by G proteins.

The receptors in the body that stimulate G proteins and increase cAMP include:

Beta (?1, ?2, and ?3)
Dopamine (D1 and D5)
Histamine (H2)
Glucagon
Vasopressin (V2).

The second messenger for the action of nitric oxide (NO) and atrial natriuretic peptide (ANP) is cGMP.

The second messengers for angiotensin and thyroid stimulating hormone are inositol triphosphate (IP3) and diacylglycerol (DAG).

After thyroid surgery, about 10-15% of patients experience a temporary subjective voice change of varying degrees. A frog in the throat or cracking of the voice, or a weak voice, are common descriptions. These modifications are only temporary, lasting a few days to a few weeks.

Swelling of the muscles in the area of the dissection, as well as inflammation and oedema of the larynx due to the dissection, or minor trauma from the tracheal tube, are all suspected causes.

On both sides of the thyroid gland, the superior laryngeal nerve (EBSLN) runs along the upper part. The muscles that fine-tune the vocal cords are innervated by these nerves. The quality of their voice is usually normal if they are injured, but making high-pitched sounds may be difficult. Injury to the EBSLN occurs in about 2% of the population.

Injuries to the recurrent laryngeal nerve (RLN) have been reported to occur in 1 percent to 14 percent of people. Except for the cricothyroid muscle, the RLN supplies all of the laryngeal intrinsic muscles.

This complication is usually unilateral and temporary, but it can also be bilateral and permanent, and it can be intentional or unintentional. The most common complication following thyroid surgery is a permanent lesion of damaged RLN, which manifests as an irreversible phonation dysfunction.

The crico-arytenoid joint dislocation is a relatively uncommon complication of tracheal intubation and blunt neck trauma. The probability is less than one in a thousand.

Vocal cord polyps affect 0.8 percent of people.

Work up bias involves comparing the novel diagnostic test with the current standard test. A portion of the patients undergo the standard test while others undergo the new test as the standard test is costly. The result can be alteration in specify and sensitivity.

Recall bias is specifically appropriate to the case control studies that is when ever the memories retrieved by the participants differ in accuracy.

Not publishing the results of a valid study just because they are negative or uninteresting can be termed as publication bias.

When information gathering is ill suited with respect to time i.e. collecting the data regarding a fatal disease many years after the death of its patients, it is termed as Late – look bias.

The case in point is an instance of lead time bias when upon comparing two tests, one is able to detect the condition earlier than the other but the overall outcome doesn’t change. There is a possibility that this will make the survival rates for the newer test look more promising.

Magnesium is a very important cation due to its various physiological roles in the body. This includes:
– playing the role of a cofactor in many enzymatic reactions
– influencing hormone receptor binding
– affecting calcium channels
– impact on cardiac, vascular and neural cells

Magnesium sulphate is used as first line in the treatment of eclampsia. Moreover, it has some preventive role in patients with severe pre-eclampsia. All the clinical effects of magnesium are in line with its plasma concentration.

The first sign of magnesium toxicity in obstetric patients is the loss of patellar reflex, which is regularly monitored during treatment. The other options are all late signs of magnesium toxicity.

Whenever there is a doubt, serum magnesium levels should always be monitored.

The table below correlates the effects of increased levels of magnesium on the body:

Plasma Concentration
(mmol/L) Effect
0.7-1.2 Normal
4-8 Decreased deep tendon reflexes, nausea, headache, weakness, malaise, lethargy and facial flushing
5-10 ECG changes (prolonged PR, prolonged QT, and widened QRS)
10 Muscle weakness, loss of deep tendon reflexes, hypotension
15 SA/AV nodal block, respiratory paralysis and depression
20 Cardiac arrest

Organophosphate poisoning occurs most often due to accidental exposure to toxic amounts of pesticides. Signs and symptoms include diarrhoea, urination, miosis, bradycardia, emesis, lacrimation, lethargy and salivation.

Organophosphates are classified as indirect acting cholinomimetics, and their mode of action involves: (1) the inhibition of acetylcholinesterase (AChE) by forming a stable covalent bond on the active site serine; and, (2) amplification of endogenously release acetylcholine (ACh), hence the clinical manifestation.

There are 4 types of bonds or interactions: ionic, covalent, hydrogen bonds, and van der Waals interactions. Ionic and covalent bonds are strong interactions that require a larger energy input to break apart. When an element donates an electron from its outer shell, a positive ion is formed. The element accepting the electron is now negatively charged. Because positive and negative charges attract, these ions stay together and form an ionic bond. Covalent bonds form when an electron is shared between two elements and are the strongest and most common form of chemical bond in living organisms. Covalent bonds form between the elements that make up the biological molecules in our cells. Unlike ionic bonds, covalent bonds do not dissociate in water.

When polar covalent bonds containing a hydrogen atom form, the hydrogen atom in that bond has a slightly positive charge. This is because the shared electron is pulled more strongly toward the other element and away from the hydrogen nucleus. Because the hydrogen atom is slightly positive, it will be attracted to neighbouring negative partial charges. When this happens, a weak interaction occurs between the slightly positive charge of the hydrogen atom of one molecule and the slightly negative charge of the other molecule. This interaction is called a hydrogen bond.

With respect to oxygen transport in cells, almost all oxygen is transported within erythrocytes. There is limited solubility and only 1% is carried as solution. Thus, the amount of oxygen transported depends upon haemoglobin concentration and its degree of saturation.

Haemoglobin is a globular protein composed of 4 subunits. Haem is made up of a protoporphyrin ring surrounding an iron atom in its ferrous state. The iron can form two additional bonds – one is with oxygen and the other with a polypeptide chain.
There are two alpha and two beta subunits to this polypeptide chain in an adult and together these form globin. Globin cannot bind oxygen but can bind to CO2 and hydrogen ions.
The beta chains are able to bind to 2,3 diphosphoglycerate. The oxygenation of haemoglobin is a reversible reaction. The molecular shape of haemoglobin is such that binding of one oxygen molecule facilitates the binding of subsequent molecules.

The oxygen dissociation curve (ODC) describes the relationship between the percentage of saturated haemoglobin and partial pressure of oxygen in the blood.
Of note, it is not affected by haemoglobin concentration.

Chronic anaemia causes 2, 3 DPG levels to increase, hence shifting the curve to the right

Haldane effect – Causes the ODC to shift to the left. For a given oxygen tension there is increased saturation of Hb with oxygen i.e. Decreased oxygen delivery to tissues.
This can be caused by:
-HbF, methaemoglobin, carboxyhaemoglobin
-low [H+] (alkali)
-low pCO2
-ow 2,3-DPG
-ow temperature

Bohr effect – causes the ODC to shifts to the right = for given oxygen tension there is reduced saturation of Hb with oxygen i.e. Enhanced oxygen delivery to tissues. This can be caused by:
– raised [H+] (acidic)
– raised pCO2
-raised 2,3-DPG
-raised temperature

Thermodilution is the most common dilution method used to measure cardiac output (CO) in a hospital setting.

During the procedure, a Swan-Ganz catheter, which is a specialized catheter with a thermistor-tip, is inserted into the pulmonary artery via the peripheral vein. 5-10mL of a cold saline solution with a known temperature and volume is injected into the right atrium via a proximal catheter port. The solution is cooled as it mixes with the blood during its travel to the pulmonary artery. The temperature of the blood is the measured by the catheter and is profiled using a computer.

The computer also uses the profile to measure cardiac output from the right ventricle, over several measurements until an average is selected.

Cardiac output changes at each point of respiration, therefore to get an accurate measurement, the same point during respiration must be used at each procedure, this is usually the end of expiration, that is the end-expiratory pause.

Accumulation of morphine-6-glucuronide is a risk factor for opioid toxicity during morphine treatment. Morphine is metabolized in the liver to morphine-6-glucuronide and morphine-3-glucuronide, both of which are excreted by the kidneys. In the setting of renal failure, these metabolites can accumulate, resulting in a lowering of the seizure threshold. However, it does not occur in all patients with renal insufficiency, which is the most common reason for accumulation of morphine-6-glucuronide; this suggests that other risk factors can contribute to morphine-6-glucuronide toxicity.

The active metabolites of codeine are morphine and the morphine metabolite morphine-6-glucuronide. The enzyme systems responsible for this metabolism are: CYP2D for codeine and UGT2B7 for morphine, codeine-6-gluronide, and morphine-6-glucuronide. Both of these systems are subject to genetic variation. Some patients are ultrarapid metabolizers of codeine and produce higher levels of morphine and active metabolites in a very short period of time after administration. These increased levels will produce increased side effects, especially drowsiness and central nervous system depression.

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

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

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

Silica hardens the granules and can thus prevent disintegration.

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

Incidence tells us about the number of new cases that have been reported while prevalence gives us the idea of existing cases.

In this particular instance, the parameter of the study i.e. the total number of cases has not changed thus the prevalence of the disease remains same. Although, more cases have been reported in the second instance as a result of which incidence has increased.

The abdominal aorta begins at the level of the body of T12 near the midline, as a continuation of the thoracic aorta. It descends and bifurcates at the level of L4 into the common iliac arteries.

An abdominal aortic aneurysm is a swelling in the abdominal aorta. It most commonly occurs in men over 65 years old of age. Smoking, diabetes, hypertension, and hypercholesterolemia are other risk factors contributing to the disease.

The NHS screening program for abdominal aortic aneurysms involves an ultrasound test for men aged 65 or over if they have not undergone screening for a one-off screening test.

This question is asking which structure would lie posterior to the rectus abdominis muscle and not the prosthetic mesh, as only peritoneum lies posterior to mesh during a total extraperitoneal (TEP) hernia repair.

The region of the repair lies below the arcuate line, meaning that the transversalis fascia and peritoneum lie posterior to the rectus abdominis.

The bucks fascia lies within the penis.

Normally, at rest vagal influence is dominant producing the heart rate of 60-80 beats per minute even if the intrinsic automaticity of Sinoatrial Node is 100-110 beats per minute.

The transplanted heart has no autonomic nervous supply. So, it will respond to endogenous and exogenous catecholamine. This loss of parasympathetic innervation is responsible for the tachycardia in this patient.

Hypokalaemia can cause myocardial excitability and potential for ventricular ectopic and supraventricular arrhythmias. Hypothyroidism is also unlikely to cause tachycardia in this patient.

At the ankle joint, midway between the malleoli, the anterior tibial artery changes names, becoming the dorsalis pedis artery (dorsal artery of the foot).

The dorsalis pedis artery is palpated against the underlying tarsals, immediately lateral to the tendon of extensor hallucis longus, from the midpoint between the malleoli to the proximal end of the first intermetatarsal space.

The popliteal artery forms the anterior tibial artery.
The tibioperoneal trunk is a branch of the popliteal artery.
The peroneal artery (also known as the fibular artery) supplies the lateral compartment of the leg.
The external iliac artery is formed from the common iliac artery at the level of the pelvis.

The anterior tibial artery originates from the distal border of the popliteus. In the posterior compartment, it passes between the heads of the tibialis posterior and the oval aperture of the interosseous membrane to reach the anterior compartment.

On entry into the anterior compartment, it runs medially along the deep peroneal nerve.
The upper third of the artery courses between the tibialis anterior and extensor digitorum longus muscles, while the middle third runs between the tibialis anterior and extensor hallucis longus muscles.

At the ankle, the anterior tibial artery is located approximately midway between the malleoli. It continues on the dorsum of the foot, lateral to extensor hallucis longus, as the dorsalis pedis artery.

The posterior cerebral arteries are the terminal branches of the basilar artery and are connected to the circle of Willis via the posterior communicating artery. The posterior cerebral artery supplies the visual areas of the cerebral cortex and other structures in the visual pathway.

The posterior cerebral artery is separated from the superior cerebellar artery near its origin by the oculomotor nerve (3rd cranial nerve) and, lateral to the midbrain, by the trochlear nerve.

PCA strokes will primarily cause a visual field loss or homonymous hemianopia to the opposite side. This large occipital or PCA stroke causes people to be “blind” on one side of the visual field. This is the most common symptom of a large occipital lesion or PCA stroke.

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.

Anticholinergic agents are a group of drugs that blocks the action of the neurotransmitter called acetylcholine at synapses in the central and peripheral nervous system.

Hyoscine, atropine, and glycopyrrolate are anticholinergic which acts at muscarinic receptors with little activity at the nicotinic receptors.

Hyoscine and atropine are naturally occurring esters. Since Glycopyrrolate is a synthetic quaternary amine, it does not cross the blood brain barrier. Noteworthy, hyoscine, butylbromide also does not cross the blood brain barrier significantly.

Observers may subconsciously measure or report data in a way that favours the expected study outcome. Therefore, by blinding the study we can eliminate expectation bias.

Recall bias is a systematic error that occurs when the study participants omit details or do not remember previous events or experiences accurately.

Verification can occur during investigations when there is a difference in testing strategy between groups of individuals, which might lead to biasness due to differing ways of verifying the disease of interest.

Nonresponse bias is the bias that occurs when the people who respond to a survey differ significantly from the people who do not respond to the survey.

A distortion that modifies an association between an exposure and an outcome because a factor is independently associated with the exposure and the outcome. Randomization is the best way to reduce the risk of confounding.

Nitroglycerine is rapidly denitrated enzymatically in the smooth muscle cell to release the free radical nitric oxide (NO).

Released NO activated cytosolic guanylyl cyclase which increases cGMP (cyclin guanosine monophosphate) which causes dephosphorylation of myosin light chain kinase (MLCK) through a cGMP-dependent protein kinase.

Reduced availability of phosphorylated (active) MLCK interferes with activation of myosin and in turn, it fails to interact with actin to cause contraction. Consequently, relaxation occurs.

Continuous closure of the vocal cords resulting in partial or complete airway obstruction is called Laryngospasm. It is a reflex that helps protect against pulmonary aspiration.

Predisposing factors include: Hyperactive airway disease, Insufficient depth of anaesthesia, Inexperience of the anaesthetist, Airway irritation, Smoking, Shared airway surgery and Paediatric patients

Its primary treatment includes checking for blood or stomach aspirate in the pharynx, removing any triggering stimulation, relieving any possible supra-glottic component to airway obstruction and application of CPAP with 100% oxygen.

In this patient, all the above has been done and the next treatment of choice is the administration of a rapidly acting intravenous anaesthetic agent such as propofol (0.5 mg/kg) in increments as it has been reported to relieve laryngospasm in approximately 75% of cases. Administering suxamethonium to an awake patient would be inappropriate at this stage.

Magnesium and lidocaine are used for prevention rather than acute treatment of laryngospasm. Superior laryngeal nerve blocks have been reported to successfully treat recurrent laryngospasm but it is not the next logical step in index patient.

PaCO2 is one of the most important factors that regulate cerebral vascular tone. CO2 induces cerebral vasodilatation and as a result, it increases CBF. Between 20 mmHg (2.7 kPa) and 80 mmHg (10.7 kPa), there is a linear increase of PaCO2.

Sometimes, there are areas where auto regulation has failed locally but not globally. Similarly, local vs. systemic acidosis will have similar effects. When the PaO2 falls below 50 mmHg (6.5 kPa), the CBF progressively increases.

An increase in the cerebral metabolic rate for oxygen (CMRO2) and therefore CBF can be caused by hyperthermia.
A late feature of cerebral injury is hyperthermia secondary to hypothalamic injury. Therefore this is not the most likely cause of an increased CBF in this scenario.

Intra-arterial blood pressure monitoring is a common place procedure in the ICU. It is used to provide accurate beat-to-beat information using a pressure wave displayed on a monitor.

It involves catheter insertion in a peripheral artery (most commonly the radial, brachial and dorsalis pedis arteries). Each subsequent contraction of cardiac muscles results in pressure wave which induces a mechanical motion of flow in the catheter. This mechanical motion is then passed on to a transducer through a rigid fluid-filled tubing. The transducer is the able to process this mechanical motion into electrical signals which are displayed as arterial waves and pressure represented numerically on the monitor.

The transducer should be placed at the same level as the heart on the phlebostatic axis, and at the level of the atria (the 4th intercostal space, in the mid-axillary line).

Air bubbles and catheter tubing with longer lengths result in wave dampening (rounding of the resulting pressure waves). This dampening causes a decrease in systolic pressure, and an increase in diastolic pressure.

Bell’s palsy is facial muscle weakness or paralysis that arises from idiopathic damage to the facial nerve. It can occur at any age but is commonly associated with some conditions:
1. pregnancy
2. diabetes
3. upper respiratory ailment
4. GBS
5. Toxins

The common symptoms of Bell’s palsy are:
1. Abnormal corneal reflex as the facial nerve controls the motor aspect of the corneal reflex.
2. The loss of control of facial muscles and eyelids leads to decreased tear production.
3. mild weakness to total paralysis on one side of the face, occurring within hours to days.
4. Bell’s palsy is a lower motor neuron lesion that usually spares the forehead while the upper motor near lesions, like stroke, involves the entire face.
5. The anterior two-thirds of the tongue is supplied by the chorda tympani branch of the facial nerve, thus resulting in loss of taste.
6. Ptosis can be a feature of Bell’s palsy but Bell’s palsy would typically show unilateral symptoms rather than bilateral.

Automated blood gas analysers are commonly used to analyse blood gas samples, and they measure specific components of the arterial blood gas sample, whether directly or indirectly.

The following are the components of arterial blood gas:

pH = measured (directly determined) acid-base balance of the blood

PaO2 = measured partial pressure of oxygen in arterial blood

PaCO2 = measured partial pressure of carbon dioxide in arterial blood

HCO3 = calculated (indirectly determined) concentration of bicarbonate in arterial blood

Base excess/deficit = calculated relative excess or deficit of base in arterial blood

SaO2 = calculated arterial oxygen saturation unless a co-oximetry is obtained, in which case it is measured

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

Once the decision to deliver a baby by caesarean section has been made, it should be carried out with a level of urgency commensurate with the risk to the baby and the mother’s safety.

There are four types of caesarean section urgency:

Category 1 – Endangering the life of the mother or the foetus
Category 2 – Maternal or foetal compromise that is not immediately life threatening
Category 3 – Early delivery is required, but there is no risk to the mother or the foetus.
Category 4: Elective delivery at a time that is convenient for both the mother and the maternity staff.

Caesarean sections for categories 1 and 2 should be performed as soon as possible after the decision is made, especially for category 1. For category 1 caesarean sections, a decision to deliver time of 30 minutes is currently used.

In most cases, Category 2 caesarean sections should be performed within 75 minutes of making the decision.

The condition of the woman and the unborn baby should be considered when making a decision for a quick delivery, as it may be harmful in some cases.

There is no evidence of foetal compromise in the example above (early foetal pulse decelerations and a pH of less than 7.25). Early foetal pulse decelerations are most likely caused by the uterus compressing the foetal head. The foetus is not harmed by these. A spinal anaesthetic is preferred over a general anaesthetic whenever possible.

If the foetal scalp blood pH is greater than 7.25, it’s a good idea to repeat the test later and look for any changes. When a foetus decelerates, the mother should be given oxygen, kept in a left lateral position, and kept hydrated to avoid the need for a caesarean section.

The reasons for adding adrenaline to a local anaesthetic solution are:

1. To Increase the duration of block
2. To reduce absorption of the local anaesthetic into the circulation
3. To Increase the upper safe limit of local anaesthetic (2.5 mg/kg instead of 2 mg/kg, in this case).

The addition of adrenaline to bupivacaine does not affect its potency, lipid solubility, protein binding, or pKa(8.1 with or without adrenaline).

The pH of bupivacaine is between 5-7. Premixed with adrenaline, it is 3.3-5.5.
The onset of a local anaesthetic and its ability to penetrate membranes depends upon degree of ionisation. Compared with the ionised fraction, unionised local anaesthetic readily penetrates tissue membranes to site of action. The onset of action of solution B is slower. this is because the relationship between pKa(8.1) and pH(3.3-5.5) of the solution results in a greater proportion of ionised local anaesthetic molecules compared with solution A.

Pituitary macroadenoma is a benign tumour with growth larger than 10mm (those under 10mm are called microadenoma)

Compression of optic chiasm by pituitary adenoma is responsible for causing visual field defects like bitemporal hemianopia, optic neuropathy.

This may be the classical case of blood transfusion reaction due to ABO incompatibility.

Here red cells are destroyed in the bloodstream with the release of haemoglobin in circulation (causing haemoglobinuria). Here, IgM or IgG anti-A or anti-B antibody can cause rapid activation of complement cascade usually the classical pathway. This is called intravascular haemolysis.

There may be extravascular haemolysis by cells of the mononuclear phagocyte system situated in the liver and spleen. Extravascular red cell destruction can increase breakdown products of haemoglobin, such as bilirubin and urobilinogen.

Also known as the “product limit estimate’’, the Kaplan-Meier survival plot is used to estimate the true survival function from the collected data.

Using this plot, probabilities of occurrence of an event at a certain point in time can be computed. The successive probabilities are multiplied by any earlier computed probabilities to get the final estimate. For a given population, the survival probability at any particular time on the plot = (number of subjects living at the start – number of subjects who died)/number of subjects living at the start.

The description of a scatter plot is a graphical representation using Cartesian coordinates to display values for more than two variables for data set. It is used for to assess the relationship between 2 different variables.

Vecuronium is used as a part of general anaesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation. It is a monoquaternary aminosteroid (not quaternary) non- depolarising neuromuscular blocking drug.

It has a structure similar to both rocuronium and pancuronium. The only difference is the substitution of specific groups on the steroid structure.

Vecuronium is not associated with the release of norepinephrine from sympathetic nerve endings. However, Pancuronium has norepinephrine releasing the property.

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.

Boyle’s law is correctly stated as it states that the volume of a gas of known mass is inversely proportional with absolute pressure, at a constant temperature.

Beer’s law states that radiation absorption by a solution of known thickness and concentration is identical to that of a solution of double thickness and half concentration.

Bougner’s (or Lambert’s) law states that every layer with the same thickness will absorb the same amount of radiation as it passes through.

Graham’s law states that the diffusion rate of a gas is inversely related to the square root of its molecular weight.

Raoult’s law states that the reduction of a solvent’s vapour pressure is directly proportional to the solute’s molar concentration.

The correlation coefficient gives us the idea about relation between two parameters. i.e. to what extent change in parameter A could prompt a change in parameter B. The numerical value of correlation coefficient could not be greater than 1.

The measure of drug potency or therapeutic response is the ED95. This is defined as the dose of a neuromuscular blocking drug required to produce a 95% depression of muscle twitch height. The ED50 and ED90 describe a depression of twitch height by 50% and 90% respectively.

The ED95 (mg/kg) of the commonly used neuromuscular blocking agents are:

suxamethonium: 0.27
rocuronium: 0.31
vecuronium: 0.04
pancuronium: 0.07
cisatracurium: 0.04
mivacurium: 0.08

Mast cell tryptase is a reliable marker of mast cell degranulation. Tryptase is a protease enzyme that acts via widespread protease-activated receptors (PARs).

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.

Coronary perfusion pressure(CPP), the difference between aortic diastolic pressure (Pdiastolic) and the left ventricular end-diastolic pressure (LVEDP), is mainly determined by the formula:

CPP = Pdiastolic -LVEDP
where
Pdiastolic is the lowest pressure in the aorta before left ventricular ejection and
LVEDP is measured directly during a cardiac catheterisation or indirectly using a pulmonary artery catheter. The pulmonary artery occlusion or wedge pressure approximates best with LVEDP.

Using this patient’s haemodynamic data:

CPP = Pdiastolic – MPAWP
COO = 70 – 12 = 58mmHg

The autonomic nervous system is divided into the sympathetic and parasympathetic nervous system. They are anatomically and physiologically different.

The sympathetic nervous system arises from the thoracolumbar outflow (T1-L5 ) at the lateral horns of grey matter of the spinal cord. Their preganglionic neurones are usually short myelinated and synapse in ganglia lateral to the vertebral column and have acetyl choline (Ach) as the neurotransmitter. Their postganglionic neurones are longer and unmyelinated and synapse with effector organ where the neurotransmitter is either adrenaline or noradrenaline.

The outflow of the parasympathetic nervous system is craniosacral. The cranial part originates from the midbrain and medulla (cranial nerves III, VII, IX and X) and the sacral outflow is from S2, S3 and S4. Their preganglionic neurones are usually long myelinated and synapse in ganglia close to the target organ and has Ach as its neurotransmitter. The unmyelinated postganglionic neurones is shorter and they synapse with effector organ. The neurotransmitter here is also Ach.

Both sympathetic and parasympathetic preganglionic neurons are cholinergic. Only the postganglionic parasympathetic neurons are cholinergic.

Attributable proportion is the proportion of disease that is caused due to exposure. It refers to the proportion of disease that would be eradicated from a particular population if the disease rate was diminished to match that of the unexposed group.

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. Thus two are not the same.

The attributable risk is the rate of a disease in an exposed group to that of a group that has not been exposed to it i.e. how many deaths did the exposure cause.

The number of osmoles (Osm) of solute per litre (L) of solution (Osmol/L) is the unit of measurement for solute concentration. The calculated serum osmolality assumes that the primary solutes in the serum are sodium salts (chloride and bicarbonate), glucose, and urea nitrogen.

2 (Na + K) + Glucose + Urea (all in mmol/L) = calculated osmolarity

313 mOsm/L = 2 (144 + 6) + 9.5 + 3.5

Sodium and potassium ions clearly contribute the most to plasma osmolarity. Glucose and urea, on the other hand, are less so.

The osmolarity of normal serum is 285-295 mOsm/L. Temperature and pressure affect osmolality, and this calculated variable is less than osmolality for a given solution.

The number of osmoles (Osm) of solute per kilogramme (Osm/kg) is a measure of osmolality, which is also a measure of solute concentration. Temperature and pressure have no effect on the value. An osmometer is used to measure it in the lab. Osmometers rely on a solution’s colligative properties, such as a decrease in freezing point or a rise in vapour pressure.

The osmolar gap (OG) is calculated as follows:

OG = osmolaRity calculated from measured serum osmolaLity

Excess alcohols, lipids, and proteins in the blood can all contribute to the difference.

30mL 0.5% bupivacaine, 1mL 1 in 1,000 adrenaline and 89mL 0.9% N. Saline is the correct answer.
Initial concentration of bupivacaine is 0.5% with a volume of 30mL

The volume is doubled (60mL) by the addition of 0.9% N. saline (30mls) and the concentration of bupivacaine is halved to (0.25%).

If the volume is doubled again (120mL) by the addition of further 0.9% N. saline (59mls) the final concentration of bupivacaine is halved again to 0.125%. Total N. saline = 89mls

The 1 mL of 1 in 1000 adrenaline has also been diluted into the final volume of 120 mL making it a 1 in 120000 concentration.

The clinical potency of the anaesthetic agent is measured using minimal alveolar concentration(MAC).

MAC and oil: gas partition coefficient is inversely related. Anaesthetic agent Oil/gas partition coefficient and Minimal alveolar concentration (MAC) is given respectively as

Desflurane 18 6
Isoflurane 90 1.2
Nitrous oxide 1.4 104
Sevoflurane 53.4 2
Xenon 1.9 71

With these data, we can conclude Isoflurane is the most potent with the highest oil/gas partition coefficient of 90 and the lowest MAC of 1.2

Iliacus, and Psoas major are the most important muscles that produce flexion at the hip.

They are collectively called the iliopsoas muscle. The iliacus muscle originates from the ilium while the psoas major muscle takes its origin from the lumbar vertebrae and sacrum. Their insertion is the lesser trochanter of the femur. They work together to produce flexion and external rotation of the hip. The nerve supply is from branches of the lumbar plexus (L1, 2, 3) femoral nerve (L2, 3, 4) and short direct muscular branches (T12, L1, L2, L3 and L4).

Sartorius, Rectus femoris, Tensor fasciae latae, and Pectineus muscles are two-joint muscles acting at the knee and having less influence on hip flexion:

Rectus femoris and sartorius are involved in extension of the knee. They are supplied by branches of the femoral nerve.

Myotomes associated with key movement of the lower limb are:

L1/L2 – Hip flexion
L2/L3/L4 – Hip adduction, quadriceps (knee extension)
L4/L5 – Hip abduction
L5 – Great toe dorsiflexion.

Since knee extension is not affected, L2, L3 and L4 are still intact.

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

Hawthorne effect explains the change in any behavioural aspect owing to the awareness that the person is being observed.
Simpson’s Paradox explains the association developed when the data from several groups is combined to form a single larger group.

The remaining terms are made up.

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.

The subclavian artery lies behind and partly above the subclavian vein. 3-4% of the time, it can be inadvertently cannulated during cannulation of the subclavian vein

Because of its anatomical position, putting pressure on the subclavian artery is impossible so arresting bleeding with pressure when it is punctured is not viable.

One of the consequences of subclavian vein cannulation (1%) is pleural puncture leading to a pneumothorax. This is because the apical pleura is inferior and caudal to the subclavian vein.

Giardiasis is known to have a longer incubation time and doesn’t cause bloody diarrhoea.

Cholera usually doesn’t cause bloody diarrhoea.

Generally, most of the E.coli strains do not cause bloody diarrhoea.

Diverticulitis can be a cause of bloody stool but the history here points out to an infectious cause.

Campylobacter infection is the most probable cause as it is characterized by a prodrome, abdominal pain and bloody diarrhoea

There are different effects of electrocution and these can be shown in the table below.

Current Effect
1 mA Tingling
5 mA Pain
15 mA Tonic muscle contraction
50 mA Respiratory arrest
100 mA Ventricular fibrillation and cardiac arrest

The half life of Retinol binding protein (RBP) is 10-12 hours and therefore reflects more acute changes in protein metabolism than any of these proteins. Therefore it is not commonly used as a parameter for nutritional assessment.

The half life of Transthyretin (thyroxine binding pre-albumin) is only one to two days and so levels are less sensitive and this protein is not an albumin precursor. 15 mg/dL represents early malnutrition and a need for nutritional support.

Albumin levels have been frequently as a marker of nutrition but this is not a very sensitive marker. It’s half life more than 30 days and significant change takes some time to be noticed. Also, synthesis of albumin is decreased with the onset of the stress response after burns. Unrelated to nutritional status, the synthesis of acute phase proteins increases and that of albumin decreases.

A more accurate indicator of protein stores is transferrin. It’s response to acute changes in protein status is much faster. The half life of serum transferrin is shorter (8-10 days) and there are smaller body stores than albumin. A low serum transferrin level is below 200 mg/dL and below 100 mg/dL is considered severe. Serum transferrin levels can also affect serum transferrin level.

Fibronectin is used a nutritional marker but levels decrease after seven days of starvation. It is a glycoprotein which plays a role in enhancing the phagocytosis of foreign particles.

A paediatric 19G Tuohy catheter is available that is 5cm in length and has 0.5cm markings

18G Tuohy catheters are generally 9 to 10cm to hub

Distal end of catheter is angled (15 to 30 degrees) and closed to avoid puncturing the dura

Epidural mesh are usually 0.2 microns and are used to filter bacteria and viruses to ensure sterility of procedure

Transparent catheters are 90cm long with diameters depending on gauge size. It has 1cm graduations from 5 to 20cm to ensure they have been inserted amply and removed completely. Distal end is smooth which can be open or closed (with lateral openings)

The bispectral index (BIS) is one of several systems used in anaesthesiology as of 2003 to measure the effects of specific anaesthetic drugs on the brain and to track changes in the patient’s level of sedation or hypnosis. It is a complex mathematical algorithm that allows a computer inside an anaesthesia monitor to analyse data from a patient’s electroencephalogram (EEG) during surgery. It is a dimensionless number (0-100) that is a summative measurement of time domain, frequency domain and high order spectral parameters derived from electroencephalogram (EEG) signals.

Sleep and anaesthesia have similar behavioural characteristics but are physiologically different but BIS monitors can be used to measure sleep depth. With increasing sleep depth during slow-wave sleep, BIS levels decrease. This correlates with changes in regional cerebral blood flow when measured using positron emission tomography (PET).

BIS shows a dose-response relationship with the intravenous and volatile anaesthetic agents. Opioids produce a clinical change in the depth of sedation or analgesia but fail to produce significant changes in the BIS. Ketamine increases CMRO2 and EEG activity.

BIS is unable to predict movement in response to a surgical stimulus. Some of these are spinal reflexes and not perceived by the cerebral cortex.

BIS is used during cardiopulmonary bypass to measure depth of anaesthesia and an index of cerebral perfusion. However, it cannot predict subtle or significant cerebral damage.

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.

Carotid endarterectomy is the procedure to relieve an obstruction in the carotid artery by opening the artery at its origin and stripping off the atherosclerotic plaque with the intima. This procedure is performed to prevent further episodes, especially in patients who have suffered ischemic strokes or transient ischemic attacks.

The external carotid artery terminates by dividing into the superficial temporal and maxillary branches. The maxillary artery is the larger of the two terminal branches and arises posterior to the neck of the mandible.

The other arteries mentioned in the answer options branch off from the following:
Temporal arteries from the maxillary artery
Middle meningeal artery from the maxillary artery
Lingual artery from the anterior aspect of the external carotid artery
Facial artery from the anterior aspect of the external carotid artery

The oxygen content of arterial blood can be calculated by the following equation:
(10 x haemoglobin x SaO2 x 1.34) + (PaO2 x 0.0225).
This is the sum of the oxygen bound to haemoglobin and the oxygen dissolved in the plasma.

Oxygen content x cardiac output = The amount of oxygen delivered to the tissues in unit time which is known as the oxygen flux.

Any factor that increases the metabolic demand will encourage oxygen offloading from the haemoglobin in the tissues and this causes the oxygen dissociation curve (ODC) to shift to the right. This subsequently reduced the oxygen content of arterial blood.

Conditions like fever, metabolic or respiratory acidosis lowers the oxygen content and shifts the ODC to the right.
A low level of 2,3 diphosphoglycerate (2,3-DPG) is usually related to an increased oxygen content as there is less offloading, and so the ODC is shifted to the left.

So for a given PaO2, a high blood oxygen content is related to any factors that can shift the ODC to the left and not to the right.

A low haematocrit usually means that there is a decreased haemoglobin concentration, and therefore is associated with decreased oxygen binding to haemoglobin.

Being the part of a meta analysis, forest plots are more valued as evidence then randomised control trials.

The notion that forest plots can only be used if the results are substantial is not true. They are good indicators of the significance of the data. If the diamond intersects the central line, the data is rendered significant. It also aggregates means and confidence intervals from studies conducted in the past which makes the study much more reliable as errors associated with individual studies tend to have less of an impact in this way.

The suggestion that forest plots are primarily used for qualitative data is factually incorrect. Forest plots require numerical values to function.

All in all, forest plots help us in determining whether or not there is a significant trend in that particular field of study.

Fractures to the surgical neck of the humerus are common place as it is the weakest point of the proximal humerus bone.

The structures most likely to be damaged are the axillary nerve and the posterior circumflex humeral artery as they surround the surgical neck.

The radial nerve runs along the radial groove, so injury to it would likely occur with a mid-shaft fracture of the humerus.

The brachial artery is most likely to be injured as a result of a supracondylar fracture of the humerus which increases the risk of volkmaan’s ischemic contractures.

Injury to the musculocutaneous nerve is least likely to happen and it very uncommon.

Impaired ventricular relaxation reduces diastolic filling and therefore preload.

Decreased blood volume decreases preload due to reduced venous return.

Heart failure is characterized by reduced ejection fraction and therefore stroke volume.

Cardiac output = stroke volume x heart rate

Left ventricular ejection fraction = (stroke volume / end diastolic LV volume ) x 100%

Stroke volume = end diastolic LV volume – end systolic LV volume

Pulse pressure (is increased by stroke volume) = Systolic Pressure – Diastolic Pressure

Systemic vascular resistance = mean arterial pressure / cardiac output
Factors that increase pulse pressure include:
-a less compliant aorta (this tends to occur with advancing age)
-increased stroke volume
Aortic stenosis would decrease stroke volume as end systolic volume would increase.
This is because of an increase in afterload, an increase in resistance that the heart must pump against due to a hard stenotic valve.

The incidence of vertebral canal haematoma following neuraxial blockade was reported (third National Audit Project (NAP3)) as 0.85 per 100 000 (95% CI 0-1.8 per 100 000). The incidence following neuraxial blockade in coagulopathic patients is likely to be higher hence coagulopathy remains a relative contraindication for conducting a spinal or epidural. When indicate, risk and benefits are weighed, and it is only performed by experienced personnel in this case.

Acceptable time to perform a block after the last dose of rivaroxaban in a patient with a creatinine clearance of greater than 30mL/minute is 18 hours.

Acceptable time to perform a block after the last dose of subcutaneous LMWH as prophylaxis is 12 hours.

Acceptable time to perform a block after the last dose of subcutaneous UFH as prophylaxis is 4 hours.

Acceptable time to perform a block after the last dose of thrombolytic therapy (streptokinase or alteplase) is 10 days.

Clopidogrel should be stopped 7 days prior to surgery, particularly if a central neuraxial procedure is considered.

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

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

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

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

The passive leg raising (PLR) manoeuvre is a method of altering left and right ventricular preload and it is done with real-time measurement of stroke volume. It is a simple, quick, relatively unbiased, and accurate bedside test to guide fluid management and avoid fluid overload.

Pulse pressure variation (PPV), Stroke volume variation (SVV), superior vena cava diameter variation (threshold 36%) and end-expiratory occlusion test are used for dynamic tests of fluid responsiveness.

PPV is derived peripherally from the arterial pressure waveform.

Stroke volume variation (SVV) can be derived peripherally through pulse contour analysis of the arterial waveform. PPV and SVV have a threshold of 12% but since they are not used in patients who have cardiac arrhythmias, are spontaneous breathing, and in ventilated patients with low lung compliance and tidal volumes, they are of limited value.

The tests of fluid responsiveness’ accuracy is determined by calculating the area under the receiver operating characteristic curve (UROC) obtained by plotting the sensitivity of the parameter in predicting fluid responsiveness vs. 1-specificity.

Under optimal conditions, the ability to determine the need for fluid is best with PPV>SVV>LVEDA>CVP.

Central venous pressure (CVP) is a static test of preload (not preload responsiveness) and a key determinant of cardiac function. The left ventricular end-diastolic area (LVEDA) a static test of fluid responsiveness, is derived using echocardiography

Selection bias is when randomisation is not achieved and is often a result of in efficient recruiting method.

Recall bias is specifically appropriate to the case control studies that is when ever the memories retrieved by the participants differ in accuracy.

Measurement bias can be characterized by gathering of information in a manner that is distorted.

When the participants of a research study are recruited from the hospitals rather than the general population, its called Berkson Bias.

Confounding bias is the major player here because in this case the effects of smoking can be masked behind and can be read as outcomes of lower socio economic status. This extraneous factor (Smoking), distorts the founding.

Both incidence and prevalence are indicators of the disease frequency. While incidence tells us about the number of cases reported per population in a provided time period, prevalence is the factor you should be vigilant about as it tells us about the total number of cases that have been reported in a population at a particular point of time.

Insulin is the primary anabolic hormone that dominates regulation of metabolism during digestive phase. It promotes glucose uptake in skeletal myocytes and adipocytes, and other insulin-target cells. It promotes glycogenesis and inhibits gluconeogenesis.

Glucagon is the primary counterregulatory hormone that increases blood glucose levels, primarily through its effects on liver glucose output.

Similar to glucagon, growth hormone, catecholamines and corticosteroids are also counterregulatory factors released in response to decreased glucose concentrations. Growth hormone promotes glycogenolysis and inhibits gluconeogenesis; catecholamines stimulate glycogenolysis and gluconeogenesis; while corticosteroids stimulate glycogenesis and gluconeogenesis.

A single chamber pacemaker was implanted in the patient. In VVI mode, a pacemaker paces and senses the ventricle while being inhibited by a perceived ventricular event. The most likely electrical hazard from diathermy is electromagnetic interference (EMI).

EMI has the potential to cause the following: Inhibition of pacing
Asynchronous pacing
Reset to backup mode
Myocardial burns, and
Trigger VF.

Diathermy entails the implementation of high-frequency electrical currents to produce heat and either make incisions or induce coagulation. Monopolar cautery involves disposable cautery pencils and electrosurgical diathermy units. In typical monopolar cautery, an electrical plate is placed on the patient’s skin and acts as an electrode, while the current passes between the instrument and the plate. Monopolar diathermy can therefore interfere with implanted metal devices and pacemaker function.

Bipolar diathermy, where the current passes between the forceps tips and not through the patient and is less likely to generate EMI.

Whilst the presence of a CVP line may in theory predispose the patient to microshock, the use of prerequisite CF electrical equipment makes this very unlikely. The presence of a CVP line and pacemaker does not therefore unduly increase the risk of an electrical hazard.

Isolating transformers are used to protect secondary circuits and individuals from electrical shocks. There is no step-up or step-down voltage (i.e. there is a ratio of 1 to 1 between the primary and secondary windings).

A ground (or earth) wire is normally connected to the metal case of an operating table to protect patients from accidental electrocution. In the event that a fault allows a live wire to make contact with the metal table (broken cable, loose connection etc.) it becomes live. The earth will provide an immediate path for current to safely flow through and so the table remains safe to touch. Being a low resistance path, the earth lets a large current flow through it when the fault occurs ensuring that the fuse or RCD will quickly blow. Without an operating table earth, the patient is not at more risk of an electrical hazard because of the pacemaker.

Barbituric acid is the barbiturates’ pharmacologically inactive precursor. A pyrimidine heterocyclic nucleus is formed by the condensation of urea and malonic acid. Its pharmacological activity can be influenced by minor structural changes (structure function relationship).

The duration of action and potency as a sedative are influenced by the length of the side chains at C5. Barbiturates with three carbon atoms in their chain last longer than those with two. Anticonvulsant properties are enhanced by branched chains.

The addition of a methyl group at N1 causes a faster onset/offset of action, but it also causes excitatory phenomena (twitching/lower convulsive threshold).

The addition of oxygen and sulphur to C2 increases the molecule’s lipid solubility and thus its potency. Thiopentone (thiobarbiturate) has sulphur groups at C2, making it 20-200 times more lipid soluble than oxybarbiturates.

The ileocolic artery is the terminal branch of the superior mesenteric artery. It supplies:
1. terminal ileum
2. proximal right colon
3. cecum
4. appendix (via its branch of the appendicular artery)

As veins accompany arteries in the mesentery and are lined by lymphatics, high ligation is the norm in cancer resections—the ileocolic artery branches off the SMA near the duodenum.

Since the data is normally distributed, 95% of the values lie with in the interval 70 to 90. This can be calculated as follows:

Interval= Mean ± ( 2 times standard deviation)
= 80 ± 2(5)
= 80 ± 10
= 70 & 90

The rest of the 5% are distributed symmetrically beyond 90 and below 70 which means 2.5% of the values lie above 90.

Body fluid compartments in a 70kg male:
Total volume=42L (60% body weight)
Intracellular fluid compartment (ICF) =28L
Extracellular fluid compartment (ECF) = 14L

ECF comprises:
Intravascular fluid (plasma) = 3L
Extravascular fluid = 11L

Extravascular fluids comprises:
Interstitial fluid = 10.5L
Transcellular fluid = 0.5L

Carbonic anhydrase is an enzyme which contains zinc and can be found in:
1. Erythrocytes
2. Pulmonary endothelium
3. The intestine
4. Pancreas
5. Cardiac muscle and skeletal muscle.

To date, there have been seven isoenzymes identified. Of note, isoenzyme IV is found in the brush border of the proximal convoluted tubule and isoenzyme II is found within the luminal cells.

Acetazolamides a carbonic anhydrase inhibitor and is used as prophylaxis against mountain sickness and in glaucoma management.

Spironolactone is a potassium diuretic and is an aldosterone antagonist.

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.

This data is in a 2 × 2 contingency table so a chi square test can be used. There is a special chi squared formula that gives a value that can be looked up in a table giving the p value.

Since we are comparing proportions not means, the Student’s t test CANNOT be used.

There is no linear regression to plot so Pearson’s co-efficient cannot be calculated.

Nothing is so obvious that no statistical analysis is needed.

Nausea and vomiting occur commonly due to Chemoreceptor Trigger Zone (CTZ) stimulation by dopamine (Domperidone but not metoclopramide can be used for the treatment of this vomiting)

Dopamine itself cannot cross the blood-brain barrier (BBB) but its precursor levodopa can cross BBB.

Dopamine can modulate extrapyramidal symptoms like acute dyskinesia, tardive dyskinesia, Parkinsonism, and Neuroleptic malignant syndrome.

Dopamine inhibits the secretion of prolactin from the pituitary gland.

The cervical plexus is a complex network of nerves within the head and neck region, providing nerve innervation to regions within the head, neck and trunk.

It is comprised of nerves arising from the anterior primary rami of the C1-C4 nerve roots.

The cervical plexus gives off superficial and deep branches. The superficial branches penetrate through the deep fascia at the centre point of the posterior border of the sternocleidomastoid. It provides sensory innervation from the lower border of the mandible to the 2nd rib. The deep branches provide motor innervation to the neck and diaphragmatic muscles.

Cervical plexus block is surgically relevant as it is used to provide regional anaesthesia for procedures in the neck region. The anaesthesia should be injected into the centre point of the posterior border of the sternocleidomastoid. Complications arise when anaesthesia is instead injected into the wrong point, including into the vertebral artery, subarachnoid and epidural spaces, blockade of phrenic and recurrent laryngeal nerves, and the cervical sympathetic plexus.

The most likely diagnosis is a spinal epidural haematoma, a neurological emergency. A full examination must be carried out to determine the nature of the neurological problem before conducting any investigations or imaging.

The effects of spinal anaesthesia should have worn off by this time point, and the severe back pain is a red flag.

The patient will also require an urgent neurological team referral as a spinal epidural haematoma requires immediate evacuation for spinal decompression. Analgesics may be prescribed for pain management.

Heparin would have been fully metabolised and so a reversal is unnecessary.

A spinal epidural haematoma is a pooling of blood in the epidural space, which can cause compression of the spinal cord. Its presenting symptoms are:

Usually begins with severe backpain and percussion tenderness
Cauda equina syndrome
Paralysis of the lower extremities.
If infected, a fever occurs in 66% of cases
Lower limb weakness developing after stopping an epidural infusion or weakness of the lower limbs which does not resolve within four hours of cessation of infusion of epidural local anaesthetic
Meningism.

Severity of a reduction in restrictive defect (%FVC) or obstructive defect (%FEV1/FVC) predicted are classified as follows:

Mild 70-80%
Moderate 60-69%
Moderately severe 50-59%
Severe 35-49%
Very severe <35% This patient has a %FVC predicted of 60.4% and this corresponds to a moderate restrictive deficit. %FEV1/FVC ratio is 93.5%. FEV1/FVC ratio 80% < predicted and VC < 80% = mixed picture. FEV1/FVC ratio 80% < predicted and VC > 80% = obstructive picture.

FEV1/FVC ratio 80% > predicted and VC > 80% = normal picture.

FEV1/FVC ratio 80% > predicted and VC < 80% predicted= restrictive picture. The integrity of the alveolar-capillary barrier is measured by carbon monoxide transfer factor (TLCO) and carbon monoxide transfer coefficient (KCO). These values are seen to be reduced in emphysema, interstitial lung diseases and in pulmonary vascular pathology. However, the KCO (as % predicted) is high in extrapulmonary restriction (pleural, chest wall and respiratory neuromuscular disease), and in loss of lung units provided the structure of the lung remaining is normal. The KCO distinguishes extrapulmonary (high KCO) causes of ‘restriction’ from intrapulmonary causes (low KCO).

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.

Propofol is a short-acting medication used for starting and maintenance of general anaesthesia, sedation for mechanically ventilated adults, and procedural sedation.
The dose of propofol is 1-2 mg/kg.

Dose of some other important drugs are listed below:
Thiopental dose: 3-7 mg/kg
Ketamine dose: 1-2 mg/kg
Etomidate dose: 0.3 mg/kg
Methohexitone dose: 1.0-1.5 mg/kg

Capnography is the non-invasive measurement and pictorial display of inhaled and exhaled carbon dioxide (CO2) partial pressure.

It is depicted graphically as the concentration of CO2 over time.

It is used in disease diagnosis, determining disease severity, assessing response to treatment and is the best method to for indicating when an endotracheal tube is placed in the trachea after intubation.

The wavelength of IR light usually absorbed by nitrous oxide is between 4.4-4.6?m (very close to that of CO2). Its absorption of wavelengths at 3.9 ?m is much weaker. It causes a measurable deficit of 0.1% for every 10% of nitrous oxide. The maximal wavelength of infrared (IR) light absorbed by carbon monoxide is 4.7 ?m. The volatile agents have strong absorption bands at 3.3 ?m and throughout the ranges 8-12 ?m.

IR light is not absorbed by oxygen (O2), but O2 and CO2 molecules are constantly colliding which interrupts the absorption of IR light by CO2. This increases the band of absorption, that is the Collison or pressure broadening). An oxygen percentage of 95 will result in a 0.5 percentage fall in CO2 measure.

IR light is also absorbed by water vapour which will result in an overlap of the absorption band, collision broadening and a dilution of partial pressure. This is why water trap and water permeable tubing is recommended for use as it reduces measurement inaccuracies.

The use of multi-gas analysers of modern gases also help reduce the effects of collision broadening.

Beer’s law is also applied in this system as an increase in the concentrations of CO2 causes a decrease in the amount of IR able to pass through the gas. This IR light is what generated the signal that is analysed for display.

The capnograph can indicate oesophageal intubation, but cannot determine if it is endotracheal or endobronchial. For this, auscultation is used.

According to the 2015 National Institute for Health and Care Excellence (NICE) Guidelines, antibiotic prophylaxis against infective endocarditis (IE) is not recommended routinely for people with any cardiac defect (corrected or uncorrected) due to lack of sufficient evidence regarding its benefits. Instead, antibiotic prophylaxis is recommended for those who are at risk of developing IE, such as those with acquired valvular heart disease with stenosis or regurgitation; hypertrophic cardiomyopathy; valve replacement; and previous IE.

The inferior mesenteric artery arises from the abdominal aorta at the level of the L3 vertebrae and supplies blood to the final third of the transverse colon, the descending colon, the sigmoid colon and the uppermost part of the rectum.

It is the artery most likely to affect the left colon.

The first rib is an atypical rib. It is short, wide, and flattened and lies in an oblique plane.

It has a small scalene tubercle on its medial border which marks the point of attachment of scalenus anterior. The lower surface lies on the pleura and is smooth.

The tubercle on the upper surface separates an anterior groove for the subclavian vein and a posterior groove for the subclavian artery and lower trunk of the brachial plexus.

Scalenus medius is attached to a roughened area posterior to the groove for the subclavian artery.

The upper surface gives attachment anteriorly to the subclavius muscle and costoclavicular ligament.

Using a lean body weight metric encompasses a more scientific approach to weight-based dosing. Lean body weight reflects the weight of all ‘non-fat’ body components, including muscle and vascular organs such as the liver and kidneys. As lean body weight contributes to approximately 99% of a drug’s clearance, it is useful for guiding dosing in obesity.

This metric has undergone a number of transformations. The most commonly cited formula derived by Cheymol is not optimal for dosing across body compositions and can even produce a negative result. A new formula has been developed that appears stable across different body sizes, in particular the obese to morbidly obese.

A practical downfall of the calculation of lean body weight (and other body size descriptors) is the numerical complexity, which may not be palatable to a busy clinician. Often limited time is available for prescribing and an immediate calculation is required. Lean body weight calculators are available online, for example in the Therapeutic Guidelines.

Using total body weight assumes that the pharmacokinetics of the drug are linearly scalable from normal-weight patients to those who are obese. This is inaccurate. For example, we cannot assume that a 150 kg patient eliminates a drug twice as fast as a 75 kg patient and therefore double the dose. Clinicians are alert to toxicities with higher doses, for example nephro- and neurotoxicity with some antibiotics and chemotherapeutics, and bleeding with anticoagulants. Arbitrary dose reductions or ‘caps’ are used to avoid these toxicities, but if too low can result in sub-therapeutic exposure and treatment failure.

Body surface area is traditionally used to dose chemotherapeutics. It is a function of weight and height and has been shown to correlate with cardiac output, blood volume and renal function. However, it is controversial in patients at extremes of size because it does not account for varying body compositions. As a consequence, some older drugs such as cyclophosphamide, paclitaxel and doxorubicin were ‘capped’ (commonly at 2 m^2) potentially resulting in sub-therapeutic treatment. Recent guidelines suggest that unless there is a justifiable reason to reduce the dose (e.g. renal disease), total body weight should be used in the calculation of body surface area, until further research is done. Little research into dosing based on body surface area has been conducted for other medicines.

Ideal body weight was developed for insurance purposes not for drug dosing. It is a function of height and gender only and, like body surface area, does not take into account body composition. Using ideal body weight, all patients of the same height and sex would receive the same dose, which is inadequate and generally results in under-dosing. For example a male who has a total body weight of 150 kg and a height of 170 cm will have the same ideal body weight as a male who is 80 kg and 170 cm tall. Both could potentially receive a mg/kg dose based on 65 kg (ideal body weight).

The basilar artery is a large vessel that is formed by the union of the vertebral arteries at the junction of the medulla and pons. It lies in the pontine cistern and follows a shallow groove on the ventral pontine surface, extending to the upper border of the pons.

The basilar artery then bifurcates into the two posterior cerebral arteries that form part of the Circle of Willis.

The external laryngeal nerve arises from the superior laryngeal nerve and provides innervation to the cricothyroid muscle.

The other muscles mentioned receive their innervations from the recurrent laryngeal nerve.

A prospective randomised double blind controlled trial against cyclizine in multiple centres is the most likely to change your practice.

Case controlled studies are efficient in identifying an association between a drug treatment and outcome and are usually conducted retrospectively. They are generally less valued than prospective randomised trials. They cannot generate incidence data, are subject to bias, have difficult selection of controls and can be made more difficult if note keeping is not reliable.

The gold standard in intervention-based studies is randomised controlled double blind trials. Its features are:

Treating all intervention groups identically
Reduction of bias by random allocation to intervention groups
Patients and researchers unaware of which treatment was given until at completion of study
Patients analysed within the group to which they were allocated, and
Analysis focused on estimating the size of the difference in predefined outcomes between intervention groups.

New healthcare interventions should be evaluated through properly designed randomised controlled trials (though there are some potential ethical disadvantages)

Conducting trials in multiple centres is an accepted way of evaluating a new drug as it may be the only way of recruiting sufficient number of patients within a reasonable time frame to satisfy the objectives of the trial. Type II statistical errors will occur if a small numbers of patients is used in study group.

An acetylcholinesterase inhibitor or anticholinesterase is a chemical that inhibits the cholinesterase enzyme from breaking down acetylcholine (ACh) therefore increasing the level and duration of action of the neurotransmitter acetylcholine(ACh).

ACh stimulates postganglionic receptors to produce the following effects:

Salivation
Lacrimation
Defecation
Micturition
Sweating
Miosis
Bradycardia, and
Bronchospasm.

Since these effects are produced by muscarine, they are referred to as muscarinic effects, and the postganglionic receptors are called muscarine receptors.

SLUD (Salivation, Lacrimation, Urination, Defecation – and emesis) is usually encountered only in cases of drug overdose or exposure to nerve gases. It is a syndrome of pathological effects indicating massive discharge of the parasympathetic nervous system.

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.

Hypochondriasis is an illness anxiety disorder, and describes excessively worriedness about the presence of a disease. While the woman is concerned about her possibility of developing motor neurone disease, she understands that no symptoms have yet appeared. Hypochondriasis involves patients who refuse to accept that they don’t have the disease, even if the results come back negative.

Late Look Bias occurs when the data is gathered or analysed at an inappropriate time e.g. when many of the subjects suffering from a fatal disease have died. This type of biasness might occur in some retrospective studies of motor neurone disease, but is not applicable to this prospective study.

In procedure bias, the researcher decides assignment of a treatment versus control and assigns particular patients to one group or the other non-randomly. This is unlikely to have occurred in this case, although it is not mentioned specifically. Of all the options, lead time-bias is a better answer.

The Hawthorne Effect refers to groups modifying their behaviour simply because they are aware of being observed. Any differences in the behaviour have not been mentioned in the question, and it is highly unlikely that a change in patient’s behaviour would have affected their length of survival in this case.

The correct option is lead-time bias. Even if the new blood test diagnoses the disease earlier, it doesn’t affect the outcome, as the survival time was still on average 43 months from the onset of symptoms in both groups. With the help of blood test, the disease was only detected 8 months earlier.

The axillary nerve arises from spinal roots C5-C6. It has both sensory and motor functions:

Sensory: Provides innervation to the skin over the lower deltoid area

Motor: Provides innervation to the teres minor (responsible for stabilisation of glenohumeral joint and external rotation of shoulder joint) and deltoid muscles (responsible for abduction of arms glenohumeral joint).

Injury to the axillary nerve will result in the patient being unable to abduct the arm beyond 15 degrees and a loss of sensory feeling over lower deltoid area.

These symptoms could also be a result of over-abduction of the arm (>90°) which would cause the head of the humerus to become dislocated.

This scenario describes rebreathing management.

Changes is exhaustion of the soda lime and a progressive rise in circuit deadspace is the most likely explanation for the capnograph.

It is important that the soda lime canister is inspected for a change in colour of the granules. Initially fresh gas flow should be increased and then if necessary, replace the soda lime granules. Other strategies include changing to another circuit or bypassing the soda lime canister after the fresh gas flow is increased.

Any other causes of increased equipment deadspace should be excluded.

Intraoperative hypercarbia can be caused by:

1. Hypoventilation – Breathing spontaneously; drugs which include anaesthetic agents, opioids, residual neuromuscular blockade, pre-existing respiratory or neuromuscular disease and cerebrovascular accident.
2. Controlled ventilation- circuit leaks, disconnection, miscalculation of patient’s minute volume.
3. Rebreathing – Soda lime exhaustion with circle, inadequate fresh gas flow into Mapleson circuits, increased breathing system deadspace.
4. Endogenous source – Tourniquet release, hypermetabolic states (MH or thyroid storm) and release of vascular clamps.
5. Exogenous source – Absorption of CO2 absorption from the pneumoperitoneum.

Propranolol is a nonselective beta-blocker with a half-life of 3 to 6 hours.

Since it is lipid-soluble it crosses the blood-brain barrier and causes Central Nervous System side effects like sedation, nightmares, and depression.

They are contraindicated in asthma, Congestive heart failure, and diabetes.

It has a large volume of distribution with no intrinsic sympathomimetic action.

The arch of aorta gives rise to three main branches:
1. Brachiocephalic artery
2. Left common carotid artery
3. Left subclavian artery

The brachiocephalic artery then gives rise to the right subclavian artery and the right common carotid artery.

The right common carotid artery arises from the brachiocephalic trunk posterior to the sternoclavicular joint.

The coeliac trunk is a branch of the abdominal aorta.
The ascending aorta supplies the coronary arteries.

An agonist is a molecule with intrinsic efficacy and affinity for a receptor. The ability of a drug-receptor interaction to produce a maximal response is referred to as intrinsic efficacy or activity. Efficacy also refers to a drug’s ability to have a therapeutic or beneficial effect. Although the potencies of morphine and fentanyl differ, they both have the same intrinsic efficacy.

The amount of drug required to produce a given effect is referred to as potency. If drug X is effective in a dose of 100 mcg, its potency is greater than if drug Y is effective in a dose of 10 mg.

The therapeutic index, also known as the margin of safety, is a ratio of the lethal or serious side effect dose of a drug divided by the therapeutic dose of the same drug.

The term bioavailability refers to the ability of a substance to be absorbed. The area under a curve (AUC) of a graphic plot of plasma concentration and time is used to calculate oral bioavailability. It’s used to figure out how much of a drug to take and when to take it.

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.

All of the muscles of the larynx are innervated by the recurrent laryngeal nerve, except the cricothyroid muscle.

Cricothyroid muscle is located deep in the anterior neck, between the cricoid and thyroid cartilage and is innervated by the external laryngeal nerve. Any injury to this muscle can cause paralysis and lead to hoarseness. When cricothyroid muscle contracts, it leads to tightening, stretching and thinning of the vocal folds. This produces higher-pitched sounds during vocalization.

A patient experiencing hoarseness due to possible injury to the external laryngeal nerve should be reassured that the hoarseness will resolve in time due to increased compensation from the other muscles.

According to the Safe Anaesthesia Liaison Group, the most important factor to consider the cannula access, and if the patient is properly receiving the total intravenous anaesthesia. The cannula access must be regularly checked for kinks, leaks and disconnections.

Below are the safety precautions and policies to be followed for total intravenous anaesthesia among children and adults:

When administering TIVA, a non-return valve must be used on any intravenous fluid line;
When using equipment, it is essential that clinical staff know its limitations and uses;
Sites of intravenous infusions should be visible so they may be monitored for disconnection, leaks or perivenous infusion into the subcutaneous tissues; and,
Organisations must give preference to clearly labelled intravenous connectors and valves.

A mercury barometer can be used to determine absolute pressure. A glass tube with one closed end serves as the barometer. The open end is inserted into a mercury-filled open vessel. The mercury in the container is pushed into the tube by atmospheric pressure exerted on its surface. Absolute pressure is the distance between the tube’s meniscus and the mercury surface.

Pressure is defined as force in newtons per unit area (F) (A). 

Mass of mercury = area (A) × density (ρ) × length (L)
Pressure = ((A × ρ × L) × 9.8 m/s2)/A
Pressure = ρ × L x 9.8
Pressure is proportional to L

The numerator and denominator of the above equation, area (A), cancel out. The constants are density and the gravitational acceleration value.

The length is proportional to the applied pressure.

The commonest and most likely cause of a gradual rise in end-tidal CO2 (EtCO2) occurring during anaesthesia in a spontaneously breathing patient is hypoventilation. This occurs from the respiratory depressant effects of the opioid and sevoflurane.

Malignant hyperthermia should be sought if the EtCO2 shows further progressive rise.

Causes of rebreathing and a rise in the baseline of the capnograph can be caused by exhausted soda lime and inadequate fresh gas flow into the Bain circuit.

A sudden rise in EtCO2 can be caused deflation of the tourniquet.

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.

The inguinal canal is the pathway leading from the wall of the abdomen to the external genitalia.

The borders of the inguinal canal are:

Anterior wall: formed by the aponeurosis of the external oblique, supported by the internal oblique muscle laterally.

Posterior wall: formed laterally by the transversalis fascia, and medially by the conjoint tendon

Roof: formed by the internal oblique and transversus abdominis muscles

Floor: formed by the inguinal ligament and supported medially by the lacunar ligament

Metabolic equivalent (MET) measures the energy expenditure of an individual.

It is calculated mathematically by:

MET = (VO2 max/weight)/3.5 = 21/3.5 = 6 METs

Where 1 MET = 3.5 mL O2/kg/minute is utilized by the body.

Note:

1 MET Eating
Dressing
Use toilet
Walking slowly on level ground at 2-3 mph
2 METs Playing a musical instrument
Walking indoors around house
Light housework
4 METs Climbing a flight of stairs
Walking up hill
Running a short distance
Heavy housework, scrubbing floors, moving heavy furniture
Walking on level ground at 4 mph
Recreational activity, e.g. golf, bowling, dancing, tennis
6 METs Leisurely swimming
Leisurely cycling along the flat (8-10 mph)
8 METs Cycling along the flat (10-14 mph)
Basketball game
10 METs Moderate to hard swimming
Competitive football
Fast cycling (14-16 mph)

Its known that 68.3% of the total values of a normally distributed variable are found within a range of 1 standard deviation from the mean which makes the range to be 4.3 to 4.9 mmol/L.

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.

This is a classical case of unstable angina or NSTEMI (Non-ST-elevation myocardial infarction). As soon as the diagnosis of unstable angina or NSTEMI is made the initial treatment is Aspirin and antithrombin therapy.

Betablocker is known to reduce mortality from acute myocardial infarction by reducing oxygen demand. If there is no contraindication (heart block, bradycardia, hypotension, severe left ventricular dysfunction, and asthma), a beta-blocker should be given early. This patient has hypotension and therefore metoprolol is contraindicated.

If three doses of nitroglycerine tablets or Nitrolingual sprays and intravenous beta-blockers too cannot relieve the symptoms intravenous Glyceryl Trinitrate (GTN) should be considered provided that there is no hypotension. But in this case, the patient is hypotensive, and therefore, it is contraindicated.

If the symptoms are not relieved after three serial doses of nitroglycerine or if symptoms recur despite adequate anti-anginal treatment morphine sulphate is indicated.

Thiopental has the longest elimination half-life of 6-15 hours.

Elimination half-life of other drugs are given as:
– Propofol: 5-12 h
– Methohexitone: 3-5 h
– Ketamine: 2 h
– Etomidate: 1-4 h

Medical gas cylinders are made up of molybdenum steel but not cast iron. They are checked and assessed at a regular interval.

At least one cylinder in each hundred are tested for tensile, pressure, smash, twist and straightening.

Nitrous Oxide cylinders contain a mixture of liquid and vapour at a pressure of approx. 4500 kPa or 45 Bar. Carbon dioxide cylinder contain gas at the pressure of 5000kPa.

The filling ratio is the ratio of mass of liquified gas in the cylinder to the mass of water required to fill the cylinder at the temperature of 15ºC. In the united kingdom, filling ratio of liquid nitrous oxide is 0.75. The cylinders are usually attached to the anaesthetic machine. As nitrous oxide is an N-methyl-d-aspartate receptor antagonist that may reduce the incidence of chronic post-surgical pain.

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

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

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

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

ANOVA is based upon within group variance (i.e. the variance of the mean of a sample) and between group variance (i.e. the variance between means of different samples). The test works by finding out the ratio of the two variances mentioned above. (Commonly known as F statistic).

Low molecular weight heparin (LMWH) creates a complex by binding to antithrombin. This complex binds with and inactivates factor Xa.

There is less risk of bleeding with LMWH because it binds less to platelets, endothelium and von Willebrand factor.

LMW binds Xa more readily. The shorter chains are less likely to bind both antithrombin and thrombin.

There is need for monitoring in renal impairment because LMHW is excreted in the urine (and partly by hepatic metabolism)

LMWH have been shown to be as efficacious as unfractionated heparin. It is also safer and have improved inpatient stay and reduced hospital cost.

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.

ICP is significant because it influences cerebral perfusion pressure and cerebral blood flow. The normal ICP ranges from 5 to 13 mmHg.

The components within the skull include the brain (80%/1400 ml), blood (10%/150 ml), and cerebrospinal fluid (CSF) (10%/150 ml).

Because the skull is a rigid box, if one of the three components increases in volume, one or more of the remaining components must decrease in volume to compensate, or the ICP will rise (Monroe-Kellie hypothesis).

Primary brain injury occurs as a result of a head injury and is unavoidable unless precautions are taken to reduce the risk of head injury. A reduction in oxygen delivery due to hypoxemia (low arterial PaO2) or anaemia, a reduction in cerebral blood flow due to hypotension or reduced cardiac output, and factors that cause a raised ICP and reduced CPP are all causes of secondary brain injury. Secondary brain injury can be avoided with proper management.

The most important initial management task is to make certain that:

There is protection of the airway and the cervical spine
There is proper ventilation and oxygenation
Blood pressure and cerebral perfusion pressure are both adequate (CPP).

Following the implementation of these management principles, additional strategies to reduce ICP and preserve cerebral perfusion are required. The volume of one or more of the contents of the skull can be reduced using techniques that can be used to reduce ICP.

Reduce the volume of brain tissue
Blood volume should be reduced.
CSF volume should be reduced.

The following are some methods for reducing the volume of brain tissue:
Abscess removal or tumour resection
Steroids (especially dexamethasone) are used to treat oedema in the brain.
To reduce intracellular volume, use mannitol/furosemide or hypertonic saline.
To increase intracranial volume, a decompressive craniectomy is performed.

The following are some methods for reducing blood volume:

Haematomas must be evacuated.
Barbiturate coma reduces cerebral metabolic rate and oxygen consumption, lowering cerebral blood volume as a result.
Hypoxemia, hypercarbia, hyperthermia, vasodilator drugs, and hypotension should all be avoided in the arterial system.
PEEP/airway obstruction/CVP lines in neck: patient positioning with 30° head up, avoid neck compression with ties/excessive rotation, avoid PEEP/airway obstruction/CVP lines in neck

The following are some methods for reducing CSF volume:

To reduce CSF volume, an external ventricular drain or a ventriculoperitoneal shunt is inserted (although more a long term measure).

Venous cutdown is a surgical procedure when venous access is difficult, and other procedures like the Seldinger technique, ultrasound-guided venous access, and intraosseous vascular access have failed.

The vein of choice for venous cutdown is the long/great saphenous vein. It is part of the superficial venous collecting system of the lower extremity. It is the preferred vein as the long saphenous vein has anatomic consistency and is superficially located at the ankle anterior to the medial malleolus. It is also the most commonly used conduit for cardiovascular bypass operations.

Origin- in the foot at the confluence of the dorsal vein of the first digit and the dorsal venous arch of the foot
Route- runs ANTERIOR to the medial malleolus and travels up in the medial leg and upper thigh.
Termination: in the femoral vein within the femoral triangle

Regarding the other options:
The short saphenous vein passes posterior to the lateral malleolus.
The dorsalis pedis vein accompanies the dorsalis pedis artery on the anterior foot.
The posterior tibial vein is part of the deep venous system accompanying the posterior tibial artery. There is no significant sural vein (there is a sural nerve), but the sural veins accompany the sural arteries and drain to the popliteal vein.

The posterior tibial artery originates from the popliteal artery in the popliteal fossa. It passes posterior to the popliteus muscle to pierce the soleus muscle. It descends between the tibialis posterior and flexor digitorum longus muscles.

The posterior tibial artery supplies blood to the posterior compartment of the lower limb. The artery can be palpated posterior to the medial malleolus.

There are 4 main pulse points for the lower limb:

1. Femoral pulse 2-3 cm below the mid-inguinal point
2. Popliteal partially flexed knee to loosen the popliteal fascia
3. Posterior tibial behind and below the medial ankle
4. Dorsal pedis dorsum of the foot over the navicular bone

Chi-square test is used to determine the statistically significant different between categorical variables. It also determines the difference between expected frequencies and the observed frequencies.

Mann Whitney U test is used to determine the statistically significant different between two independent groups.

Wilcoxon’s test is the test of dependency. it determines the statistically significant difference between two dependent groups.

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.

ANOVA (analysis of variance) is similar to student’s t-test.

ANOVA is a statistical method used to determines the statistically significant difference between the mean of more than two group. In this experiment as we are dealing with three different group, ANOVA is most suitable test to determine the difference between each groups.

When there is a fall in ionised plasma calcium levels, the chief cells of the parathyroid glands are stimulated to secrete parathyroid hormone (PTH).

50% of extracellular calcium occurs as non-ionised, protein- (albumin-)bound calcium.

The degree of ionisation increases with low ph and decreases with high pH.

There is increased renal calcium excretion with secretion of calcitonin.

The inguinal canal is a passage in the lower anterior abdominal wall just above the inguinal ligament. It transmits the following structures:
1. genital branch of genitofemoral nerve
2. ilioinguinal nerve
3. spermatic cord (males only)
4. round ligament of the uterus (females only)

The ilioinguinal is a direct branch of the first lumbar nerve. The ilioinguinal nerve enters the inguinal canal via the abdominal musculature (and not through the deep (internal) inguinal ring) and exits through the superficial (or external) inguinal ring.

The openings for the other nerves in the answer options are:
Sciatic nerve – exits the pelvis via the greater sciatic foramen
Obturator nerve – descends into pelvis via the obturator foramen
Femoral nerve – descends from the abdomen through the pelvis behind the inguinal canal

The Iliohypogastric nerve also arises from the first lumbar root with the ilioinguinal nerve but pierces the transversus abdominis muscle posteriorly, just above the iliac crest, and continues anteriorly between the transversus abdominis and the internal abdominal oblique muscles.

Cardiac output = stroke volume x heart rate

Left ventricular ejection fraction = (stroke volume / end diastolic LV volume ) x 100%

Stroke volume = end diastolic LV volume – end systolic LV volume

Pulse pressure = Systolic Pressure – Diastolic Pressure

Systemic vascular resistance = mean arterial pressure / cardiac output
Factors that increase pulse pressure include:
-a less compliant aorta (this tends to occur with advancing age)
-increased stroke volume

Eye damage is the most common potential hazard associated with laser energy. Everyone in the laser treatment room has the risk of eye exposure when working with a Class 3b or Class 4 healthcare laser system, and damage to various structures in the eye depending on wavelength of the laser if they are unprotected.

Red and near-infrared light (400-1400 nm) has very high penetration power. The light causes painless burns on the retina after it is absorbed by melanin in the pigment epithelium just behind the photoreceptors.

Infrared radiation (IR), or infrared light (>1060 nm), is a type of radiant energy that’s invisible to human eyes and hence won’t elicit the protective blink.

Ultraviolet light (<400 nm) is also a form of electromagnetic radiation which is can penetrate the cornea and be absorbed by the iris or the pupil and cause burn injuries or cataract occur due to irreversible photochemical retinal damage. Safety eyewear is the best method of providing eye protection and are designed to absorb light specific to the laser being used. Laser protective eyewear (LPE) includes glasses or goggles of proper optical density (OD). The lenses should not be glass or plastic. The LPE should withstand direct and diffuse scattered laser beams. The laser protection supervisor (LPS) or LSO is an individual who is responsible for any clinical area in which lasers are used. They are expected to have a certain level of equipment and determine what control measures are appropriate, for each individual system, but their presence does not guarantee the chances of having an eye injury. Class 1 lasers are generally safe under every conceivable condition and is not likely to cause any eye damage. Class 3b or Class 4 medical laser systems are utilized in healthcare which have their own safety precautions. Polarized spectacles can make your eyes more comfortable by eliminated glare, however, they will not be able to offer any protection against wavelengths at which laser act.
Using short bursts to reduce energy is also not correct as it would still be harmful to eye.

The AV node has an intrinsic firing rate of 40-60 beats per minute which is clinically significant in cases of damage to the conducting pathways as patients continue to have a ventricular rate of 40-60. Patients who have an AV node supplied by the right coronary are said to be right dominant. The remaining 10% are left dominant and supplied by the left circumflex.

The right coronary artery supplies the right atrium, right ventricle, interatrial septum, and the inferior posterior third of the interventricular septum. It also supplies the atrioventricular node + sinoatrial node in most patients. The posterior descending artery supplies the posterior third of the interventricular septum.

The heart receives blood supply from coronary arteries. The right and left coronary arteries branch off the aorta and supply oxygenated blood to all heart muscle parts.

The left main coronary artery branches into:
1. Circumflex artery – supplies the left atrium, side, and back of the left ventricle. The left marginal artery arises from the left circumflex artery. It travels along the obtuse margin of the heart.
The left marginal artery, a branch of the circumflex artery, supplies the left ventricle.
2. Left Anterior Descending (LAD) artery – supplies the front and bottom of the left ventricle and front of the interventricular septum

The right coronary artery branches into:
1. Right marginal artery
2. Posterior descending artery

The perfect glomerular filtration marker is:

The human body is not harmed by it.
Chemical or physical methods are used to accurately measure
Extracellular fluid (ECF) compartment is freely and evenly diffusible.
Inability to access the intracellular fluid (ICF) compartment
Filtration in the kidney is the only way to remove it from the blood.

The ideal marker should not be reabsorbed into the bloodstream by the renal tubules or other urinary system components.

Creatinine is an endogenous substance that is filtered freely by the glomerulus and secreted by the proximal tubule. As a result, creatinine clearance consistently underestimates GFR. In healthy people, this overestimation ranges from 10% to 40%, but it is higher and more unpredictable in patients with chronic kidney disease.

The gold standard method of inulin clearance necessitates an intravenous infusion and several hours of timed urine collection, making it costly and time-consuming. Inulin is hard to come by and is difficult to mix and keep as a solution.

Exogenous filtration markers include the following:

Although plasma clearance of 51chromium EDTA is a widely used method in Europe, tubular reabsorption can occur.
Because 125I-iothalamate can be excreted by renal tubules in the urine, it cannot be used in patients who have an iodine assay.

Radioactive substances must be stored, administered, and disposed of according to these methods.

The glomerulus filters para-aminohippuric acid (PAH) freely, and any that remains in the peritubular capillaries is secreted into the proximal convoluted tubules. This marker is used to determine the amount of blood flowing through the kidneys.

In an adult, the trachea is approximately 15 cm long. It extends at the level of the 6th cervical vertebra, from the lower border of the cricoid cartilage.

The trachea terminates between T4 and T6 at the carina or bronchial bifurcation. This variation is because of changes during respiration.

The trachea has 16-20 C-shaped cartilaginous rings that maintain its patency.

The trachea is first of the 23 generations of air passages in the tracheobronchial tree (not 25), from the trachea to the alveoli..

The inferior thyroid arteries which are branches of the thyrocervical trunk, arise from the first part of the subclavian artery and supplies the trachea.

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.

The degree of correlation is summarised by the correlation coefficient (r). This indicates how closely the points lie to a line drawn through the plotted data. In parametric data this is called Pearson’s correlation coefficient and can take any value between -1 to +1. A correlation of -1.0 indicates a perfect negative correlation, and a correlation of 1.0 indicates a perfect positive correlation.

For example

r = 1 – strong positive correlation (e.g. systolic blood pressure always increases with age)

r = 0 – no correlation (e.g. there is no correlation between systolic blood pressure and age)

r = – 1 – strong negative correlation (e.g. systolic blood pressure always decreases with age)

Whilst correlation coefficients give information about how one variable may increase or decrease as another variable increases they do not give information about how much the variable will change. They also do not provide information on cause and effect.

In contrast to the correlation coefficient, linear regression may be used to predict how much one variable changes when a second variable is changed.

Krebs’ cycle (tricarboxylic acid cycle or citric acid cycle) is a sequence of reactions to release stored energy through oxidation of acetyl coenzyme A (acetyl-CoA). Some of the products are carbon dioxide and hydrogen atoms.

The sequence of reactions, known collectively as oxidative phosphorylation, only occurs in the mitochondria (not cytoplasm).

The Krebs cycle can only take place when oxygen is present, though it does not require oxygen directly, because it relies on the by-products from the electron transport chain, which requires oxygen. It is therefore considered an aerobic process. It is the common pathway for the oxidation of carbohydrate, fat and some amino acids, required for the formation of adenosine triphosphate (ATP).

Pyruvate enters the mitochondria and is converted into acetyl-CoA. Acetyl-CoA is then condensed with oxaloacetate, to form citrate which is a six carbon molecule. Citrate is subsequently converted into isocitrate, alpha-ketoglutarate, succinyl-CoA, succinate, fumarate, malate and finally oxaloacetate.

The only five carbon molecule in the cycle is Alpha-ketoglutarate.

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.

Among the types of muscles, cardiac muscles have the greatest number if mitochondria due to the heart energy requirements.

Approximately 35% of the cardiac muscle volume is due to the mitochondria. While in skeletal and smooth muscles, it comprises 3-8% of the muscle volume.

Type I muscle fibre has a slow contraction velocity, with a red fibre colour, and predominantly uses oxidative phosphorylation to produce a sustained contraction. It contains more mitochondria and myoglobin than type II, and is often used for endurance training.

Type II muscle fibre has a fast contraction velocity, a white fibre colour, and predominantly uses anaerobic glycolysis. It has fewer mitochondria and myoglobin, and is often used for weight or resistance training and sprinting.

The common peroneal (fibular) nerve descends obliquely along the lateral side of the popliteal fossa to the fibular head, medial to biceps femoris.

The sural nerve exits at the fossa’s lower inferolateral aspect and is more at risk in short saphenous vein surgery.

The tibial nerve lies more medially and is even less likely to be injured in this location.

The boundaries of the popliteal fossa are:
Superolateral – the biceps femoris tendon
Superomedial – semimembranosus reinforced by semitendinosus
Inferomedial and inferolateral – medial and lateral heads of gastrocnemius

The contents of the Popliteal fossa are:

1. The popliteal artery
2. The popliteal vein
3. The Tibial nerve and common Fibular nerve
4. Posterior femoral cutaneous nerve: descends and pierces the roof
5. Small saphenous vein
6. popliteal lymph nodes
7. fat

A significant early feature of the metabolic response to trauma and surgery is hyperglycaemia. It is due to an increased glucose production and decreased glucose utilisation bought on by neuroendocrine stimulation. Catecholamines, Growth hormone, ACTH and cortisol, and Glucagon are all increased.

There is also a decreased insulin sensitivity peripherally and an inhibition of insulin production from the beta cells of the pancreas. These changes lead to hyperglycaemia.

The stress response to endoscopic surgery will only be prevented with use of high dose opioids or central neuraxial block at anaesthesia.
To reduce the risk of inducing hyperchloremic acidosis, Ringer’s lactate/acetate or Hartmann’s solution is preferred to 0.9% sodium chloride as routine maintenance fluids.

Though it has been suggested that administration of Hartmann’s solution to patients with type 2 diabetes leads to hyperglycaemia, one Litre of Hartmann’s solution would yield a maximum of 14.5 mmol of glucose. A rapid infusion of this volume would increase the plasma glucose by no more than 1 mmol/L..

Dexamethasone, a glucocorticoid, produces hyperglycaemia by stimulating gluconeogenesis . Glucocorticoids are agonists of intracellular glucocorticoid receptors. Their effects are mainly mediated via altered protein synthesis via gene transcription and so the onset of action is slow. The onset of action of dexamethasone is about one to four hours and therefore would NOT contribute to the hyperglycaemia in this patient in the time given.

0.9% Normal saline with or without adrenaline is the usual irrigation fluid. With this type of surgery, systemic absorption is unlikely to occur.

Fentanyl is not likely the primary cause of hyperglycaemia in this patient. In high doses (50 mcg/Kg) it has been shown to reduce the hyperglycaemic responses to surgery.

In the Child-Pugh classification system, the following 5 components are determined or calculated in order:

Ascites

Grade of encephalopathy

Serum bilirubin (?mol/L)

Serum Albumin (g/L)

Prothrombin time or INR

Raised liver enzymes are not the component of the classification system.

The following terms are used in medical testing:

True negative – The test is negative and the patient does not have the disease.
True positive – The test is positive and the patient has the disease.
False positive – The test is positive but the patient does not have the disease.
False negative – The test is negative but the patient has the disease.

The sensitivity of a predictive test = true positives / (true positives + false negatives).

The specificity of a test = true negatives / (false positives + true negatives).

The negative predictive value of a test = true negatives / (false negatives + true negatives).