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

With regards to the autonomic nervous system (ANS)

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

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

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

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

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

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

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

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

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

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

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

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

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

The lacrimal glands are solely under parasympathetic control.

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

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

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

The inguinal triangle of Hesselbach’s is an important clinical landmark on the posterior wall of the inguinal canal. It has the following relations:
Inferiorly – medial third of the inguinal ligament
Medially – lower lateral border of the rectus abdominis
Laterally – inferior epigastric vessels

Direct inguinal hernia is when the bowel bulges directly through the abdominal wall. These hernias usually protrude through Hesselbach’s triangle

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

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

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

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

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

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

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

ARR= (Risk factor associated with the new drug group) — (Risk factor associated with the currently available drug)

So,

ARR= (24/120)-(60/240)

ARR= 0.2-0.25

ARR= 0.05 (Numerical Value)

ARR= 5%

Ketamine is the substance in question. Its structure and pharmacodynamic effects make it a one-of-a-kind intravenous induction agent. The molecule is made up of two cyclohexanone rings (2-(O-chlorophenyl)-2-methylamino cyclohexanone and 2-(O-chlorophenyl)-2-methylamino cyclohexanone). Ketamine has local anaesthetic properties and acts primarily on the brain and spinal cord.

It affects Ca2+ channels as a non-competitive antagonist for the N-D-methyl-aspartate (NMDA) receptor. It also acts as a local anaesthetic by interfering with neuronal Na+ channels.

Ketamine causes profound dissociative anaesthesia (profound amnesia and analgesia) as well as sedation.

Phenoxybenzamine, an alpha-1 adrenoreceptor antagonist, is an example of an irreversible competitive antagonist. It forms a covalent bond with the calcium influx receptor.

Benzodiazepines are GABAA receptor agonists that affect chloride influx.

Flumazenil is an inverse agonist that affects GABAA receptor chloride influx.

Ketamine is a cyclohexanone derivative that acts as a non-competitive Ca2+ channel antagonist.

Sevoflurane is highly fluorinated methyl isopropyl ether widely used as an inhalational anaesthetic. It is suggested that sevoflurane preconditioning occurs via the opening of mitochondrial Potassium ATP dependent channel similar to that of Ischemic Preconditioning protection.

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

SVR = (MAP-CVP)/CO x 80

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

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

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

= (10 – 5)/5 x 80 = 80 dynes.s.cm-5

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

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

The bispectral index (BIS) monitors works to determine the level of consciousness of a patient by processing electroencephalographic (EEG) signals to obtain a value between 0 and 100, where 0 reflects no brain activity, and 100 reflects a patient is completely awake.

The general meaning of BIS values are:

>95: Patient is in an awake state.
65-85: Patient is in a sedated state.
40-65: Patient is in a state that is optimal for general surgery.
<40: Patient is in a deep hypnotic state It is important in measuring the depths of anaesthesia to prevent haemodynamic changes or patient awareness during surgery. The nature of anaesthetic agent used is a determinant factor in resultant BIS values. Intravenous agents, such as propofol, thiopental and midazolam, result in a deeper hypnotic state, whilst inhalation agents have a lesser hypnotic effect at the same BIS values. Certain agents result in inaccurate BIS values such as ketamine and nitrous oxide (NO). These two agents appear to increase the BIS value, whilst putting the patient in a deeper hypnotic state, and should therefore not be used with BIS monitoring. Hypothermia also affects the BIS value as it causes a 1.12 per °C decrease in body temperature.

The extrinsic pathway is considered as the main pathway of coagulation cascade.

Heparin is known to inhibit the activation of coagulation factors 2,9,10, and 11.

The extrinsic and intrinsic pathways meet at the activation of coagulation factor 10.

Fibrinogen is converted into Fibrin in the presence of Thrombin. Plasminogen is converted into plasmin during fibrinolysis to breakdown fibrin clot.

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

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

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

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

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

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

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

The glucose molecule enters the Bowman’s capsule freely and becomes part of the filtrate.

All glucose is reabsorbed in the proximal convoluted tubule when blood glucose concentrations are below a certain threshold (approximately 11 mmol/L) (PCT). Active transportation makes this possible. In the proximal tubular cells, sodium/glucose cotransporters (SGLT1 and SGLT2) are the proteins responsible.

Glucose does not normally appear in the urine below the renal threshold.

The renal glucose threshold is not set in stone and is affected by a variety of factors, including GFR, TmG, and the quantity of splay.

The different absorptive and filtering capacities of individual nephrons cause splay, which is the rounding of a glucose reabsorption curve.

The SGLT proteins have a high affinity for glucose, but not an infinite affinity. As a result, some glucose may escape reabsorption before the TmG. A decrease in renal threshold may be caused by an increase in splay.

Because the filtered glucose load is reduced and the PCT can reabsorb all of the filtered glucose despite hyperglycaemia, a low GFR causes an increase in TmG. In contrast, lowering the TmG lowers the threshold because the tubules’ ability to reabsorb glucose is reduced.

A reduction in GFR caused by severe dehydration and reduced perfusion pressure is the most obvious cause of the discrepancy between plasma and urinary glucose in this scenario.

Phase 0 trials assist the scientists in studying the behaviour of drugs in humans by micro dosing patients. They are used to speed up the developmental process. They have no measurable therapeutic effect and efficiency.

Phase 1 is associated with assessing whether a drug is safe to use or not. The process is extensive and can take up to several months. It also involves healthy participants (less than 100) that are paid to take part in the study. The side effects upon increasing dosage are also addressed by the study. The effects the drug has on humans including how its absorbed, metabolized and excreted are studied. Approximately 70% of the drugs pass this phase.

Phase 2 trials involve patients that are suffering from the disease under study and are associated with determining the efficiency and the optimum dosage of the drug.

Phase 3 also assesses the efficacy but at a higher scale with larger population sample.

Phase 4 trials are involved with the long term effects and side effects of the drug.

A major source of caloric expenditure and oxygen consumption in the body is work of breathing (WOB) and 70% of this is to overcome elastic forces. The remaining 30% is for flow-resistive work

In a normal patient breathing normally, the total area of hysteresis pressure volume curve represents the flow-resistive WOB.

The area of the expiratory resistive work increases during an asthma attack making the compliance curve larger in area. The larger the area the greater the work required to breathe.

The question mentions a quantitative, ratio scale data set. The use of mean would be ideal under normal circumstances, however, in this situation median is preferred as it is less sensitive to the skewness of data. The median is usually preferred to other measures of central tendency when your data set is skewed (i.e., forms a skewed distribution)

Glycolysis occurs in the cytoplasm of the cell. It converts 1 glucose molecule (6-carbon) to pyruvate (two 3-carbon molecules) and produces 4 ATP molecules and 2NADH but uses 2 ATP in the process with an overall net energy production of 2 ATP.

Pyruvate is then oxidised to acetyl coenzyme A (generating 2 NADH per pyruvate molecule). This takes place in the mitochondria and then enters the Krebs cycle (citric acid cycle). It produces 2 ATP, 8 NADH and 2 FADH2 per glucose molecule.

Electron transport phosphorylation takes place in the mitochondria. The aim of this process is to break down NADH and FADH2 and also to pump H+ into the outer compartment of the mitochondria. It produces 32 ATP with an overall net production of 36ATP.

In anaerobic respiration which occurs in the cytoplasm, pyruvate is reduced to NAD producing 2 ATP.

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.

Mid-shaft fractures of the humerus usually occur after a direct blow to the upper arm, which can occur after a fall or RTAs.
The most important clinical significance of a mid-shaft humeral fracture is an injury to the radial nerve. The radial nerve originates from the brachial plexus and has roots of C5-T1. It crosses the spiral groove on the posterior side of the shaft of the humerus.
On examination, the patient may have a wrist drop, loss or weakness of finger extension, and decreased or absent sensation to the posterior forearm, digits 1 to 3, and the radial half of the fourth digit.

The humeral shaft has two compartments:
1. Anterior:
Brachial artery and vein
Biceps brachii, brachialis, coracobrachialis
Musculocutaneous, median, and ulnar nerves
2. Posterior:
Radial nerve
Triceps

Other significant nerve injuries are:
1. Axillary nerve – surgical neck fracture of the humerus
2. Brachial Artery – supracondylar fracture of the humerus
3. Axillary artery – surgical neck fracture of the humerus, but is relatively uncommon

After a paediatric case, you’ll frequently have to calculate and prescribe maintenance fluids. The ‘4-2-1 rule’ should be used as a guideline:

1st 10 kg – 4 ml/kg/hr
2nd 10 kg – 2 ml/kg/hr
Subsequent kg – 1 ml/kg/hr

Hence

1st 10 kg = 4 × 10 = 40 ml
2nd 10 kg = 2 × 10 = 20 ml
Subsequent kg = 1 × 1 = 1 ml
Total = 61 ml/hr

61 × 12 = 732 ml over 12 hrs.

An intra-operative air embolism occurs when air becomes trapped in the blood vessels during surgery.

A transoesophageal echocardiography (OE) uses invasive echocardiography to monitor the integrity and performance of the heart. It is the gold standard as it provides real-time imaging of the heart to enable early diagnosis and treatment.

Precordial doppler ultrasonography can also be used to detect into-operative air emboli. It is non-invasive and more practical, but is less sensitive.

A change in end-tidal CO2 could be indicative of and increase in physiological dead-space, but could also be indicative of any processes that reduces the excretion or increases the production of CO2, making it non-specific.

A transoesophageal stethoscope can be used to listen for the classic mill-wheel murmur produced by a large air embolus.

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.

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 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 superficial inguinal ring is an opening in the aponeurosis of the external oblique muscle, just above and lateral to the pubic crest.

The superficial ring resembles a triangle more than a ring with the base lying on the pubic crest and its apex pointing towards the anterior superior iliac spine. The sides of the triangle are crura of the opening in the external oblique aponeurosis. The lateral crura of the triangle is attached to the pubic tubercle. The medial crura of the triangle is attached to the pubic crest.

The external oblique aponeurosis forms the anterior wall of the inguinal canal and also the lateral edge of the superficial inguinal ring. The rectus abdominis lies posteromedially, and the transversalis posterior to this.

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

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

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

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

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

Patient symptom according to the hyponatremia level is correlated below:

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

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

The common peroneal (fibular) nerve is a peripheral nerve in the lower limb. It arises of the L4-S2 nerve roots and has sensory and motor innervations:

Sensory: Provides innervation of the lateral leg and foot dorsum.

Motor: Provides innervation of the short head of the biceps femoris, as well as muscles of the anterior and lateral leg compartments.

It is the most commonly damaged nerve in the lower extremity, as it is easily compressed by a plaster cast or injured when the fibula is fractured.

Damage to the common peroneal nerve will result in loss of dorsiflexion at ankle (footdrop, as feet are permanently plantarflexed), with the accompanying high stepping gait.

The saphenous and sural nerve only provide sensory innervation.

The tibial nerve arises from the sciatic nerve (like the common peroneal), but it provides motor innervation to the posterior leg compartments and intrinsic foot muscles. Injury to the tibial nerve will cause loss of plantar flexion, toe flexion and weakened foot inversion.

Extreme hip flexion into the lithotomy or Lloyd-Davies position can result in stretch damage to the neurones (sciatic and obturator nerves) or by applying direct pressure (femoral nerve compression).

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

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

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

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

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

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

The two types of lactic acidosis that are known are:

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

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

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

In resistant cases, peritoneal dialysis can be performed.

The diaphragm divides the thoracic cavity from the abdominal cavity. Structures penetrate the diaphragm at different vertebral levels through openings in the diaphragm to communicate between the two cavities. The diaphragm has openings at three vertebral levels:

T8: vena cava, terminal branches of the right phrenic nerve
T10: oesophagus, vagal trunks, left anterior phrenic vessels, oesophageal branches of the left gastric vessels
T12: descending aorta, thoracic duct, azygous and hemi-azygous vein

The solid state of matter has a definite volume and shape and particles are packed closely together and are incompressible. Within this tight lattice, there is enough thermal energy to produce vibration of particles.

Liquids however have a volume but no definite shape. These particles are less tightly packed together. Although there is free movement within the volume, they are incompressible.

Gases, however, have no finite shape or volume and particles are free to move rapidly in a state of random motion. They are compressible and are completely shaped by the space in which they are held. Vapours exist as a gas phase in equilibrium with identical liquid or solid matter below its boiling point.

The most prevalent state of matter in the universe is plasma which is formed by heating atoms to very high temperatures to form ions.

Mesenteric ischemia is ischemia of the blood vessels of the intestines. It can be life-threatening especially if the small intestine is involved.

A critical factor for survival of acute mesenteric ischemia is early diagnosis and intervention. Angiography uses X-ray and contrast dye to image arteries and identify the severity of ischemia or obstruction.

The celiac axis is the first branch of the abdominal aorta and supplies the entire foregut (mouth to the major duodenal papilla). It arises at the level of vertebra T12. It has three major branches:
1. Left gastric
2. Common hepatic
3. Splenic arteries

There are some important landmarks of vessels at different levels of vertebrae that need to be memorized.

T12 – Coeliac trunk

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

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

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

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

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

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

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

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= (0.04-0.03)

ARR= 0.01

NNT= 1/0.01

NNT=100

Selective ?1 -Blockers like prazosin, terazosin, doxazosin, and alfuzosin cause a decrease in blood pressure with lesser tachycardia than nonselective blockers (due to lack of ?2 blocking action.

The major adverse effect of these drugs is postural hypotension. It is seen with the first few doses or on-dose escalation (First dose effect).

Its half-life is approximately three hours.

It is excreted primarily through bile and faeces (not through kidneys)

Cardiac conduction

Phase 0 – Rapid depolarization. Opening of fast sodium channels with large influx of sodium

Phase 1 – Rapid partial depolarization. Opening of potassium channels and efflux of potassium ions. Sodium channels close and influx of sodium ions stop

Phase 2 – Plateau phase with large influx of calcium ions. Offsets action of potassium channels. The absolute refractory period

Phase 3 – Repolarization due to potassium efflux after calcium channels close. Relative refractory period

Phase 4 – Repolarization continues as sodium/potassium pump restores the ionic gradient by pumping out 3 sodium ions in exchange for 2 potassium ions coming into the cell. Relative refractory period

The portal vein arises from the splenic and mesenteric veins, and is the biggest vessel in the portal venous system, accounting for about 75% of the hepatic blood flow.

It is responsible for draining blood from parts of the gastrointestinal system, the spleen, the pancreas and the gallbladder into the liver.

The porta hepatis is a fissure in the inferior surface of the liver. All the neurovascular structures that enter and leave the porta hepatis are:
1. hepatic portal vein
2. hepatic artery
3. hepatic ducts
4. hepatic nerve plexus (It contains the sympathetic branch to the liver and gallbladder and the parasympathetic, hepatic branch of the vagus nerve.)

These structures supply and drain the liver. Only the hepatic vein is not part of the porta hepatis.
The porta hepatis is also surrounded by lymph nodes, that may enlarge to produce obstructive jaundice.
These structures divide immediately after or within the porta hepatis to supply the functional left and right lobes of the liver.

The cystic duct lies outside the porta hepatis and is an important landmark in laparoscopic cholecystectomy.

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

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

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

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

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

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

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

The 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.

Ketamine is primarily used for the induction and maintenance of anaesthesia. It induces dissociative anaesthesia. But it is contraindicated in cardiovascular diseases such as unstable angina or poorly controlled hypertension.

Tricyclic antidepressants (TCA) are primarily used as antidepressants which is important for the management of depression. These are second-line drugs next to SSRI. They work by competitively preventing re-uptake of amines (noradrenaline and serotonin) from the synaptic cleft so increasing their concentration. But TCA overdoses are toxic and have cardiovascular effects, central effects, and anticholinergics effects. Cardiovascular effects like prolonged QT and widened QRS at lower doses progressing to ventricular arrhythmias and refractory hypotension at higher doses can be life-threatening. When used in the perioperative period, it can lead to increased sensitivity to circulating catecholamines therefore care is needed perioperatively.

Creatinine clearance is a test used to approximate the glomerular filtration rate (GFR) as an assessment of kidney function.

Creatinine is formed during the breakdown of dietary sources of meat and skeletal muscle. It is secreted at a consistent concentration and pace into the body’s circulation, and is easily filtered across the glomerulus without being reabsorbed or metabolized by the kidney.

It is represented mathematically as:
Creatinine clearance (CL) = U x V/P
where,
U: Urinary creatinine concentration (mg/mL)
V: Volume of urine (mL/min)
P: Plasma creatinine concentration (mg/mL)

Therefore, in this case:
CL: 1.25 x 1 = 125mL/min
0.1

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.

Blood vessels (except capillaries and venules) have three distinctive layers (innermost to outermost):
1. Tunica intima
2. Tunica media
3. Tunica adventitia

The tunica media contains smooth muscle cells and is separated from the intima layer by the internal elastic lamina and the adventitia by the external elastic lamina.

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.

The upper limb venous drainage is divided into superficial and deep. The superficial veins are accessible to draw blood for investigations. The cephalic, basilic, and median cubital veins are superficial veins.

The median cubital vein connects the cephalic vein and basilic vein. It is located anteriorly in the antecubital fossa and is preferred for venepuncture due to its palpability and ease of access.

The basilic vein and cephalic vein are the primary veins that drain the upper limb. They begin as the dorsal venous arch. The basilic vein originates from the ulnar side, while the cephalic vein originates from the radial side of the dorsal arch of the upper limb.

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.

The hindgut is from the distal third of the transverse colon down to the upper one-third of the anal canal. The inferior mesenteric artery supplies the hindgut.

The inferior mesenteric artery arises from the aorta behind the inferior border of the third part of the duodenum 3–4 cm above the aortic bifurcation, at the third lumbar vertebra level.

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

T12 – Coeliac trunk

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

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.

The sternocleidomastoid muscle divides the neck into anterior and posterior triangles on both sides of the neck.

The posterior triangle has the following boundaries:
anteriorly – sternocleidomastoid muscle
posteriorly – trapezius
roof – investing layer of deep cervical fascia
floor – prevertebral fascia overlying splenius capitis, levator scapulae, and the scalene muscles

The contents of the posterior triangle are:
1. fat
2. lymph nodes (level V)
3. accessory nerve
4. cutaneous branches of the cervical plexus – greater auricular nerve, transverse cervical nerve, lesser occipital nerve, supraclavicular nerve (A major branch of this plexus is the phrenic nerve, which arises from the anterior divisions of spinal nerves C3-C5)
5. inferior belly of omohyoid
6. branches of the thyrocervical trunk (transverse cervical and suprascapular arteries)
7. third part of the subclavian artery
8. external jugular vein

The tracheobronchial tree is subdivided into the conducting and the respiratory zones.

The zones from proximal to distal are:

Trachea
Bronchi
Bronchioles
Terminal bronchioles
Respiratory bronchioles
Alveolar ducts
Alveolar sacs

from the trachea to terminal bronchioles are the conducting zone while the respiratory zone is from the respiratory bronchioles to the alveola sacs

T3 is produced by peripheral de-iodination of T4. It is more active than T4.

TBG, like most binding proteins, is increased in pregnancy. Because of this, measurement of free thyroid hormone concentration is more important than total.

T4 and T3 concentrations are decreased in Illness and starvation.

L-T4 that is the active molecule while D-T4 is inactive.

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

The clinical signs suggest a class II haemorrhage – 15-30% of circulating blood volume has been lost.

Pelvic fractures are associated with significant concealed haemorrhage (>2000 ml) and may require aggressive fluid resuscitation. Other priorities include stabilisation of the fracture(s) and pain relief.

The Advanced Trauma Life Support (ATLS) classification of haemorrhagic shock is as follows:

Class I haemorrhage (blood loss up to 15%):
<750 ml of blood loss
Minimal tachycardia
No changes in blood pressure, RR or pulse pressure
Normally not require fluid replacement as will be restored in 24 hours, but in trauma correct.

Class II haemorrhage (15-30% blood volume loss):
Uncomplicated haemorrhage requiring crystalloid resuscitation
Represents about 750 – 1500 ml of blood loss
Tachycardia, tachypnoea and a decrease in pulse pressure (due to a rise in diastolic component due action of catecholamines)
Minimal systolic pressure changes
Anxiety, fright or hostility
Can usually be stabilised by crystalloid, but may later require a blood transfusion.

Class III haemorrhage (30-40% blood volume loss):
Complicated haemorrhagic state in which at least crystalloid and probably blood replacement are required
Classical signs of inadequate perfusion, marked tachycardia, tachypnoea, significant changes in mental state and measurable fall in systolic pressure
Almost always require blood transfusion, but decision based on patient initial response to fluid resuscitation.

Class IV haemorrhage (> 40% blood volume loss):
Preterminal event patient will die in minutes
Marked tachycardia, significant depression in systolic pressure and very narrow pulse pressure (or unobtainable diastolic pressure)
Mental state is markedly depressed
Skin cold and pale
Need rapid transfusion and immediate surgical intervention.

Loss of >50% results in loss of consciousness, pulse and blood pressure.

The route of choice is an arm vein (cephalic) with one or two large bore cannula. This will enable initial aggressive fluid resuscitation. A central line can be inserted at a later stage if central venous monitoring is deemed necessary. If a suitable peripheral vein cannot be cannulated with a large bore cannula then the internal jugular vein could be accessed rapidly (preferably ultrasound guided).

Intravenous access below the diaphragm in this case is inadvisable when other routes are available.

Dopamine (DA) is a dopaminergic (D1 and D2) as well as adrenergic ? and ?1 (but not ?2 )agonist.

The D1 receptors in renal and mesenteric blood vessels are the most sensitive: i.v. infusion of a low dose of DA dilates these vessels (by raising intracellular cyclic adenosine monophosphate).

Moderately high doses produce a positive inotropic (direct ?1 and D1 action + that due to NA release), but the little chronotropic effect on the heart.

Vasoconstriction (?1 action) occurs only when large doses are infused.

At doses normally employed, it raises cardiac output and systolic BP with little effect on diastolic BP. It has practically no effect on nonvascular ? and ? receptors; does not penetrate the blood-brain barrier – no Central nervous system effects.

Dopamine is less arrhythmogenic than adrenaline

Regarding dopamine part of the dose is converted to Noradrenaline in sympathetic nerve terminals.

The dose-response curve plots the graph of the dose (drug concentration) versus the response. As doses increase, the response increment diminishes; finally, doses may be reached at which no further increase in response can be achieved. This relation between drug concentration and effect is traditionally described by a hyperbolic curve. When the x-axis is plotted in log scale, the graph yields a sigmoid curve.

Efficacy (Emax) and potency (EC50) can be derived from this curve. Emax is the maximal effect achievable, with increasing concentration of a drug. EC50 is the concentration of the drug, wherein half of the maximal effect is achieved.

When the graph is plotted using a log [response/1-response] against log dose, the sigmoid curve becomes a straight line (Hill plot). A graph that transforms from a straight line to exponential curve is mathematically incorrect. A graph that transforms from either a wash-in or wash-out exponential curve to a straight line comes from an initial set of data plotted against time, to a logarithmic transformation of the initial data set against time.

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

Hypoxic Pulmonary vasoconstriction (HPV) reflects the constriction of small pulmonary arteries in response to hypoxic alveoli (.i.e.; PO2 below 80-100mmHg or 11-13kPa).

These blood vessels become independent of the nerve stimulus, when blood with a high PO2 flows through the lung which contains a low alveolar PO2.

Thus a low PO2 within the alveoli has been shown to impact on hypoxic pulmonary vasoconstriction (HPV) more than a low PO2 within the blood.

HPV results in the blood flow being directed away from poorly ventilated areas of the lung and helps to reduce the ventilation/perfusion mismatch (not increase).

In animals, volatile anaesthetic agents can diminish HPV, while in adults, the evidence proves less persuading, in spite of the fact that it certainly doesn’t strengthen the effects.

HPV response will be suppressed by 20 parts per million (ppm) of nitric oxide.

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.

Tetracyclines inhibit protein synthesis through reversible binding to bacterial 30s ribosomal subunits (not 50s) which prevent binding of new incoming amino acids (aminoacyl-tRNA) and thus interfere with peptide growth.

They penetrate macrophages and are thus a drug of choice for treating infections due to intracellular organisms.

Tetracycline does not inhibit transpeptidation. Meanwhile, it is chloramphenicol which is responsible for inhibiting transpeptidation.

Tetracycline can get deposited in growing bone and teeth due to its calcium-binding effect and thus causes dental discoloration and dental hypoplasia. Due to this reason, they should be avoided in pregnant or lactating mothers.

Simultaneous administration of aluminium hydroxide can impede the absorption of tetracyclines.

Always call for help early. This patient is at risk of gastro-oesophageal reflux, which is why a rapid sequence induction has been chosen. The patient is not pregnant, and the surgery is not urgent.

Plan A is to perform a rapid sequence induction under optimal conditions and secure the airway with a tracheal tube.

No more than three attempts with a direct laryngoscope (plus one attempt with a videolaryngoscope) should be made to intubate the trachea. Keep in mind that suxamethonium is wearing off. Ensuring adequate neuromuscular blockade at this stage is crucial; this might include administering a non-depolarizing relaxant if oxygenation can be maintained with bag-mask ventilation. Given the non-immediate nature of the surgery, there should be a low threshold to abandon intubation attempts and resort to Plan B.

An alternative strategy can then be planned.

The most important initial step is to declare a “failed intubation.” This will prevent further intubation attempts and alert your assistant that Plan A has failed. Maintaining oxygenation and anesthesia is also critical before implementing Plan B.

Do not administer another dose of suxamethonium. Insert a supraglottic airway if oxygenation fails and adequate ventilation cannot be maintained.

Plan D follows the declaration of a CICO (Cannot Intubate, Cannot Oxygenate) situation.

The hormone parathyroid hormone (PTH) and the receptor parathyroid hormone type 1 (PTH1-Rc) are important regulators of blood calcium homeostasis.

PTH can cause a rapid release of calcium from the matrix in bone, but it also affects long-term calcium metabolism by acting directly on bone-forming osteoblasts (by binding to PTH1-Rc) and indirectly on bone-resorbing osteoclasts.

PTH causes changes in the synthesis and/or activity of several proteins, including osteoclast-differentiating factor, also known as TRANCE or RANKL, when it acts on osteoblasts.

RANK receptors are found on the cell surfaces of osteoclast precursors. The osteoclasts are activated when RANKL binds to the RANK receptors. Osteoclasts lack PTH receptors, whereas osteoblasts do. Osteoclasts are activated indirectly when the RANK receptor binds to the RANKL secreted by osteoblasts, resulting in bone resorption. PTH1 receptors are found in osteoclasts, but they are few.

PTH activates G-protein coupled receptors in all target cells via adenylate cyclase.

The PTH2 receptor is most abundant in the nervous system and pancreas, but it is not a calcium metabolism regulator. It is abundant in the septum, midline thalamic nuclei, several hypothalamic nuclei, and the dorsal horn of the spinal cord, as well as the cerebral cortex and basal ganglia. Expression in pancreatic islet somatostatin cells is the most prominent on the periphery.

The distribution of the receptor is being used to test functional hypotheses. It may play a role in pain modulation and hypothalamic releasing-factor secretion control.

Myoglobin is a haemoglobin-like, iron-containing pigment that is found in muscle fibres. It has a high affinity for oxygen and it consists of a single alpha polypeptide chain. It binds only one oxygen molecule, unlike haemoglobin, which binds 4 oxygen molecules.

The myoglobin ODC is a rectangular hyperbola. There is a very low P50 0.37 kPa (2.75 mmHg). This means that it needs a lower P50 to facilitate oxygen offloading from haemoglobin. It is low enough to be able to offload oxygen onto myoglobin where it is stored. Myoglobin releases its oxygen at the very low PO2 values found inside the mitochondria.

P50 is defined as the affinity of haemoglobin for oxygen: It is the PO2 at which the haemoglobin becomes 50% saturated with oxygen. Normally, the P50 of adult haemoglobin is 3.47 kPa(26 mmHg).

Foetal haemoglobin has 2 ? and 2 ?chains. The ODC is left shifted – this means that P50 lies between 2.34-2.67 kPa [18-20 mmHg]) compared with the adult curve and it has a higher affinity for oxygen. Foetal haemoglobin has no ? chains so this means that there is less binding of 2.3 diphosphoglycerate (2,3 DPG).

Carbon monoxide binds to haemoglobin with an affinity more than 200-fold higher than that of oxygen. This therefore decreases the amount of haemoglobin that is available for oxygen transport. Carbon monoxide binding also increases the affinity of haemoglobin for oxygen, which shifts the oxygen-haemoglobin dissociation curve to the left and thus impedes oxygen unloading in the tissues.

In sickle cell disease, (HbSS) has a P50 of 4.53 kPa(34 mmHg).

Randomisation can be used to provide control over the confounding variables during the design stage of a study however during analytical stage a technique called stratification is used for controlling confounding variables. Since the question asks for the information that is factually incorrect.

Dose response curves are plotted as % response to drug against Logarithm of drug concentration. The graph is usually sigmoid shaped.

Any drug that has high affinity and high intrinsic activity is likely an agonist. A drug with high affinity but no intrinsic activity will act as an antagonist. Displacement of an agonist also depends on the relative concentrations of the two drugs at the receptor sites.

Maximal response may be achieved by activation of a small proportion of receptor sites.

Heme a exists in cytochrome a and heme c in cytochrome c; they are both involved in the process of oxidative phosphorylation. 5′-Aminolevulinic acid synthase (ALA-S) is the regulated enzyme for heme synthesis in the liver and erythroid cells.

There are two forms of ALA Synthase, ALAS1, and ALAS2.

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

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

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

Other scalars include:

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

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

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

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.

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 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.
2. Left Anterior Descending (LAD) artery – supplies the front and bottom of the left ventricle and front of the interventricular septum

The left anterior descending coronary artery is the largest coronary artery. It courses anterior to the interventricular septum in the anterior interventricular groove, extending from the base of the heart to its apex. Around the apex, the LAD anastomosis with the terminal branches of the posterior descending artery (branch of the right coronary artery).
Atherosclerosis or thrombotic occlusion of LAD causes myocardial infarction in large areas of the anterior, septal, and apical portions of the heart muscle. It can lead to a serious deterioration in heart performance.

Occlusion of the LAD causes anteroseptal myocardial infarction, which is evident on the ECG with changes in leads V1-V4. Occlusion of the left circumflex artery causes lateral, posterior, or anterolateral MI. However, as it does not run towards the apex in the interventricular septum of the heart, it is not the correct answer for this question.

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

The right coronary artery supplies the right atrium, right ventricle, interatrial septum, and the inferior posterior third of the interventricular septum. Occlusion of the right coronary artery causes inferior MI, which is indicated on ECG with changes in leads II, III, and aVF.

When the eye is compressed or the extra-ocular muscles are tractioned, the oculocardiac reflex causes a decrease in heart rate.

The ophthalmic division of the trigeminal nerve provides the afferent limb. This synapses with the vagus nerve’s visceral motor nucleus in the brainstem. The efferent signal is carried by the vagus nerve to the heart, where increased parasympathetic tone reduces sinoatrial node output and slows heart rate.

The most common symptom is sinus bradycardia, but junctional rhythm and asystole can also occur.

The maximum safe amount of bupivacaine is 2mg/kg. Addition of adrenaline slows down absorption of the local anaesthetic and allows a maximum dose of 2.5mg/kg to be used.

The maximum safe dose of bupivacaine for this patient is 125 mg.

A 0.125% solution will contain 0.125g/100mL or 125mg/100 mL.

The maximum volume of local anaesthetic is approximately 80-100 mL.

A ‘double blind crossover study’ happens when every patient receive both treatments.

It is incorrect to say that only half of the patients do not know which treatment they receive because in a double blind placebo control clinical trial ALL of the patients are blind to their treatment choice .

If some of the patients are not treated, they would be aware that they were not being treated and it could not be considered a blind trial.

In a double blind placebo control clinical trial both the clinician and the patient are blind to the treatment choice. The clinician assessing the effects of the treatment, therefore, does not know which treatment the patient has been given.

The wall of an artery has three layers: (innermost to outermost)
1. Tunica intima – in direct contact with the blood inside the vessel and contains endothelial cells separated by gap junctions.
2. Tunica media – contains smooth muscle cells and is separated from the intima by the internal elastic lamina and the adventitia by the external elastic lamina.
3. Tunica adventitia – contains the vasa vasorum, fibroblast, and collagen.

Aortic dissection is when a tear arises in the innermost layer of the aorta and penetrates through the tear, entering the media layer. The inner and middle layers of the aorta split (dissect).

Detsky’s Modified cardiac risk classification system in patients undergoing non-cardiac surgery:

Age more than 70: 05 points

History of myocardial infarction:

Less than 6 months: 10 points
More than 6 months: 5 points

Angina Pectoris:

Angina with minimal exertion: 10 points

Angina at any level of exertion: 20 points

Pulmonary Oedema:

Within 7 days: 10 points
At any time: 5 points

Suspected aortic valve stenosis with valve area <0.6cm2: 20 points Arrhythmia: Any rhythm other than sinus or sinus with premature atrial complexes (PACs): 5 points More than 5 premature ventricular contractions: 5 points
Emergency Surgery: 10 points
Deficient general medical condition: 5 points

Risk classification:

Grade I: 0-15 points = low risk
Grade II: 15-30 points = moderate risk
Grade III: >30 points = high risk

At rest, the heart has the greatest a-vO2 difference, a high capillary to myocyte ratio, short diffusion distances, and a high mitochondrial density. The flow of blood through the coronary arteries is also tightly controlled. At rest, 70-80 percent of the oxygen available to the cardiac muscle is extracted, increasing to 90 percent during exercise.

The a-vO2 difference indicates the body’s or an individual organ’s ability to extract oxygen from the blood.

CaO2 is influenced by a number of factors, including Hb concentration, PaO2 and pulmonary diffusion capacity.

CvO2 is influenced by a number of factors, including capillary density, regional blood flow, heart, resting skeletal muscle, kidney, intestine and skin.

Tachyphylaxis is the swiftly declining response to successive drug doses which vastly reduces its effectiveness in a short space of time, mostly as a result of an acute consumption of neurotransmitters.

Tolerance or desensitisation is the slow decline in a person’s reaction to a drug due to continued use. It requires a longer time span than tachyphylaxis, usually over days or weeks.

Down- regulation is a reduction in the amount of receptors available on target cells which decreases the affinity of the agent to the cells. For this to occur, the down-regulation of receptors must occur at a rate faster than receptor synthesis. This down-regulation often occurs with beta1 receptors due to:

1) The transportation or receptors from the cell surface to the interior of the cell

2) Degradation of receptors occurring over time.

In this case, dobutamine is prescribed to treat cardiogenic shock. It is able to function by binding to beta1-adrenergic receptors to increase the contraction of the heart, thereby improving cardiac output. It also binds to beta2- and alpha1-adrenergic receptors to balance out the effects produced by binding to beta1 receptors and reduce the risk of system vasculature responses.

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.

The femoral triangle is a wedge-shaped area found within the superomedial aspect of the anterior thigh. It is a passageway for structures to leave and enter the anterior thigh.

Superior: Inguinal ligament
Medial: Adductor longus
Lateral: Sartorius
Floor: Iliopsoas, adductor longus and pectineus

The contents include: (medial to lateral)
Femoral vein
Femoral artery-pulse palpated at the mid inguinal point
Femoral nerve
Deep and superficial inguinal lymph nodes
Lateral cutaneous nerve
Great saphenous vein
Femoral branch of the genitofemoral nerve

Ciprofloxacin belongs to the quinolone group of antibiotics, and doxycycline and minocycline are tetracyclines. So, they are not affected by beta-lactamase.
However, amoxicillin is a beta-lactam antibiotic and beta-lactamase cleaves the beta-lactam ring present in amoxicillin. This results in the breakdown of the antibiotic and thus the area of erythema dramatically increased.
Co-amoxiclav contains amoxicillin and clavulanic acid which protects amoxicillin from beta-lactamase.

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

The internal laryngeal nerve lies inferior to the piriform recess mucous membrane, placing it at high risk of irritation or damage by sharp foreign objects which become lodged in the recess.

Any attempt to retrieve lodged foreign objects must be done careful as there is also a high risk of damage during this process.

The other mentioned nerves are not at risk of being affected.

The Number Needed to Treat (NNT) is the number of patients you need to treat to prevent one additional bad outcome. For example, if a drug has an NNT of 5, it means you have to treat 5 people with the drug to prevent one additional bad outcome.

To calculate the NNT, you need to know the Absolute Risk Reduction (ARR); the NNT is the inverse of the ARR:

NNT = 1/ARR

Where ARR = CER (Control Event Rate) – EER (Experimental Event Rate).

NNTs are always rounded up to the nearest whole number.

In this case, the NNT can be computed as follows:

ARR = 10% – 5% = 0.05

NNT = 1/0.05 = 20

The Mapleson A (Magill) and coaxial version of the Mapleson A system (Lack circuit) are more efficient for spontaneous breathing than any of the other Mapleson circuits. The fresh gas flow (FGF) required to prevent rebreathing is slightly greater than the alveolar minute ventilation (4-5 litres/minute). This is delivered to the patient through the outer coaxial tube and exhaust gases are moved to the scavenging system through the inner tube. In the Lack circuit, the expiratory valve is located close to the common gas outlet away from the patient end. This is the main advantage of the Lack circuit over the Mapleson A circuit.

The Mapleson E circuit is a modification of the Ayres T piece and the FGF required to prevent rebreathing is 1.5-2 times the patient’s minute volume.

The Bain circuit is the coaxial version of the Mapleson D circuit.

The FGF for spontaneous respiration to avoid rebreathing is 160-200 ml/kg/minute.

The FGF for controlled ventilation to avoid rebreathing is 70-100 ml/kg/min.

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

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

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

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

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

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

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

The apex of an equilateral triangle completed by the posterior superior iliac spines is where the sacral hiatus or sacrococcygeal membrane can normally located. The failure of posterior fusion of the laminae of the fourth and fifth sacral vertebrae allows the sacral canal to be accessible via the membrane.

In adults, the spine of L4 usually lies on a line drawn between the highest points of the iliac crests (Tuffier’s line). A line connecting each anterior iliac spine, approximates to the L3/4 interspace in the sitting position. Both of these options are incorrect.

A line connecting the greater trochanters is also incorrect.

A line connecting the posterior superior iliac spines is correct, but in adults the presence of a sacral fat pad can still make identification of this landmark less straightforward.

The processes of S5 are remnants only and form the sacral cornua, which are also used to help identify the sacral hiatus.

The ascending cervical artery lies media the phrenic nerve on scalenus anterior and can easily be mistaken for the phrenic nerve at operation.

The phrenic nerve passes across scalenus anterior and medius inferiorly.

The subclavian artery is separated from the vein by the scalenus anterior.

The brachiocephalic vein is formed at the medial border of scalenus anterior by the subclavian vein and the internal jugular vein.

Emerging from the lateral border of scalenus anterior are the trunks of the brachial plexus .

Drug A is a pure agonist for the receptor, with high intrinsic efficacy and affinity, according to the log-dose response curve.

Drug B, on the other hand, works as a competitive antagonist. It binds to the receptor but has no inherent efficacy. Drug A’s efficacy will not change, but its potency will be reduced.

A partial agonist is a drug with partial intrinsic efficacy and affinity for the receptor. Giving a partial agonist after a pure agonist will not increase receptor occupancy or decrease receptor activity, and thus will not affect drug A’s efficacy. The inverse agonist flumazenil can reverse all benzodiazepines.

An inverse agonist is a drug that binds to the receptor but has the opposite pharmacological effect.

A non-competitive antagonist is a drug that has affinity for a receptor but has different pharmacological effects and reduces the efficacy of an agonist for that receptor.

Elimination of phenytoin from the body follows first-order kinetics. This means that the rate of elimination is proportional to plasma concentration.

The rate of elimination can be described by the equation:

C = C0·e-kt

Where:

C = drug concentration
C0 = drug concentration at time zero (extrapolated)
k = Rate constant
t = Time

Enzyme systems become saturated when phenytoin concentrations exceed the normal range and elimination of the drug becomes zero-order. At this point, the drug is metabolised at a fixed rate and metabolism is independent of plasma concentration.

Aspirin and ethyl alcohol are other drugs that behave this way.

A higher frequency ultrasound comes with a better resolution of the digital image. Ultrasound with a frequency of 15 MHz is best used in imaging of superficial organs such as the thyroid gland, muscles, tendons and breasts whereas deep organs are better imaged using a lower frequency of 2-7MHz because of its ability for deeper penetration but lower resolution. These low frequency probes are also used to diagnose ascites, pleural effusions or can be used in echocardiography.

The US probe emits and then absorbs a reflected wave. Similar to brightness control, increasing the gain will amplify the return signal which is then attenuated by the tissue. This increases the signal to noise ratio.
A high frame rate, which basically means the number of times an image is updated onto the screen per second, improves the resolution of a moving 3D image which has become more accurate as the computing power has increased.

Widening of the image field can be obtained by altering the penetration depth which is obtained by changing the frequency of the US beam

Because of the low pH in the stomach, paracetamol absorption is minimal (pKa value is 9.5). Paracetamol is absorbed quickly and completely in the alkaline environment of the small intestine. Oral bioavailability is approaching 100%. As a result, measuring paracetamol levels in plasma after an oral paracetamol dose has been used as a surrogate marker of gastric emptying. This method has been used to investigate the effects of drugs on gastric emptying. At clinically used doses, paracetamol is ideal because it has very few side effects.

Scintigraphic imaging is the gold standard for determining gastric emptying.

Although aspirin (acetyl salicylic acid) is absorbed primarily in the small intestine, some may also be absorbed in the stomach. The oral bioavailability ranges from 70 to 100 percent, making it less reliable than paracetamol.

Propranolol is a lipophilic drug that is rapidly absorbed after administration. However, it is highly metabolised by the liver in the first pass, and only about 25% of propranolol reaches the systemic circulation. It’s not the best indicator of gastric emptying.

Oral bioavailability of gentamicin and vancomycin is low. Only antibiotic-induced pseudomembranous colitis is treated with oral vancomycin.

Erythromycin is a pro-kinetic agent that acts as a motilin receptor agonist.

The option that is most responsible is the progressive decrease in venous return of blood to the right atrium. The heart rate does not usually change with PEEP so the fall in cardiac output is due to a reduction in left ventricular (LV) stroke volume (SV).

Note that the interventricular septum does shift toward the left and there is an increased pulmonary vascular resistance (PVR) from overdistention of alveolar air sacs that contribute to the reduction in cardiac output. Any increase in PVR will be associated with reduced pulmonary vascular capacitance.

Prednisolone 5 mg is the same as 20 mg hydrocortisone.

Prednisolone 40 mg is the same as 8 x 20 mg or 160 mg of prednisolone.

Mineralocorticoid effects and variations in action duration are not taken into account in these comparisons.

5 mg of prednisolone is the same as Dexamethasone 750 mcg, Hydrocortisone 20 mg, Methylprednisolone 4 mg, and Cortisone acetate 25 mg.

The process used in the study is Delphi method. This method kicks off with an open ended questionnaire and uses its responses as a survey instrument for the next round in which each of the participants is asked to rate the items that the investigators have summarized on the basis of the data collected in the first round.

Any disagreement is further discussed in phases to come on the basis of information obtained from previous phases.

Smallest drops reach not only the upper but also the lower respiratory tracks. As a result, the ultrasonic nebulizer is most efficient for the therapy of pulmonary diseases and stands out as a robust and reliable support within the clinical setting.