Phenytoin, Carbamazepine, and Valproate act by inhibiting the sodium channels when these are open. These drugs also prolong the inactivated stage of these channels (Sodium channels are refractory to stimulation till these reach the closed/ resting phase from inactivated phase)

Carbamazepine is the drug of choice for partial seizures and trigeminal neuralgia

It can have neurotoxic side effects. Major neurotoxic effects include dizziness, headache, ataxia, vertigo, and diplopia

After single oral doses of carbamazepine, the absorption is fairly complete and the elimination half-life is about 35 hours (range 18 to 65 hours). During multiple dosing, the half-life is decreased to 10-20 hours, probably due to autoinduction of the oxidative metabolism of the drug.

It is metabolized in liver into active metabolite, carbamazepine-10,11-epoxide.

Classification of hemorrhagic shock according to Advanced Trauma Life Support is as follows:

– Class I haemorrhage (blood loss up to 15%) in which there is no change in blood pressure, RR, or pulse pressure.

– Class II haemorrhage (15-30% blood volume loss) where there is tachycardia, tachypnoea, and a decrease in pulse pressure.

– Class III haemorrhage (30-40% blood volume loss) where clinical signs of inadequate perfusion, marked tachycardia, tachypnoea, significant changes in mental state, and measurable fall in systolic pressure is seen. It almost always requires a blood transfusion.

– Class IV haemorrhage (> 40% blood volume loss) in which marked tachycardia, significant depression in systolic pressure and very narrow pulse pressure, and markedly depressed mental state with cold and pale skin are seen.

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

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..

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

The standard error of the mean (SEM) is a measure of the spread expected for the mean of the observations – i.e. how ‘accurate’ the calculated sample mean is from the true population mean. The relationship between the standard error of the mean and the standard deviation is such that, for a given sample size, the standard error of the mean equals the standard deviation divided by the square root of the sample size.

SEM = SD / square root (n)

where SD = standard deviation and n = sample size

After ingestion of more than 150 mg/kg paracetamol within 24 hours, hepatotoxicity can occur but can also develop rarely after ingestion of doses as low as 75 mg/kg within 24 hours. Hepatocellular damage will not occur in this patient and therefore no need to engage management pathway for paracetamol overdose. If his weight was <33 kg or he already had a history of impaired liver function, then the management would bde different. Subsequent post-operative doses will be a standard dose of 1 g 6 hourly. This is a drug administration error and should be reported as an incident even though the patient will not be harmed.

During fetal development, blood oxygenated by the placenta flows to the foetus through the umbilical vein, bypasses the fetal liver through the ductus venosus, and returns to the fetal heart through the inferior vena cava.

Blood returning from the inferior vena cava then enters the right atrium and is preferentially shunted to the left atrium through the patent foramen ovale. Blood in the left atrium is then pumped from the left ventricle to the aorta. The oxygenated blood ejected through the ascending aorta is preferentially directed to the fetal coronary and cerebral circulations.

Deoxygenated blood returns from the superior vena cava to the right atrium and ventricle to be pumped into the pulmonary artery. Fetal pulmonary vascular resistance (PVR), however, is higher than fetal systemic vascular resistance (SVR); this forces deoxygenated blood to mostly bypass the fetal lungs. This poorly oxygenated blood enters the aorta through the patent ductus arteriosus and mixes with the well-oxygenated blood in the descending aorta. The mixed blood in the descending aorta then returns to the placenta for oxygenation through the two umbilical arteries.

A post-tetanic count of 5 denotes a deep neuromuscular blockade.

Post tetanic count (PTC) is a well-established method of evaluating neuromuscular recovery during intense neuromuscular blockade. It cam ne used when there is no response to single twitch, tetanic, or train-of-four (TOF) stimulation to assess the intensity of neuromuscular blockade and to estimate the duration after which the first twitch in the TOF (T1) is likely to reappear.

During a nondepolarizing block, the high frequency of tetanic stimulation will induce a transient increase in the amount of acetylcholine released from the presynaptic nerve ending, such that the intensity of subsequent muscle contractions will be increased (potentiated) briefly (period of post-tetanic potentiation, which may last 2 to 5 min. The neuromuscular response to stimulation during post tetanic potentiation can be used to gauge the depth of block when TOF stimulation otherwise evokes no responses. The number of post tetanic responses is inversely proportional to the depth of block: fewer post tetanic contractions denote a deeper block. When the post tetanic count (PTC) is 6 to 8, recovery to TOF count = 1 is likely imminent from an intermediate-duration blocking agent; when the PTC is 0, the depth of block is profound, and no additional NMBA should be administered.

The cylindrical structure(spine), starts from the foramen magnum in medulla oblongata at the skull’s base. Its length varies in gender with men having 45cm and women having up to 43 cm. The spine contains 31 pairs of spinal nerves, named according to the spinal region:
– 8 cervical nerve pairs ( C1-C8)
– 12 thoracic nerve pairs ( T1-T12)
– 5 lumbar nerve pairs (L1-L5)
– 5 sacral nerves (S1-S5) and
– 1 coccygeal nerve pair.
These spinal nerves are classified as the peripheral nervous system though they branch from the spinal cord and central nervous system. They interact directly with the spinal cord to modulate the motor and sensory information from the peripheral’s region. As the nerves emerges form the spinal cords they are known as rootlets. They join to form nerve roots, and depending on their position, we have anterior nerve roots and posterior.

The spinal cord is supplied by two posterior and one anterior spinal arteries which anastomoses caudally, at the conus medullaris.

The anterior spinal artery supplies the anterior two-thirds of the spinal cord and medulla. Disruption of the anterior spinal artery supply is characterised by ischaemia or infarction of motor tracts (corticospinal) and loss of pain and temperature sensation below the level of the lesion.

The posterior spinal arteries supply the posterior columns (posterior third of the spinal cord). Infarction of the posterior columns results in the loss of proprioceptive, vibration and two-point discrimination.

The spinal cord normally ends at the level of L1 or L2 in an adult and L3 in a newborn.

Gentamicin is a broad-spectrum antibiotic whose mechanism of action involves inhibition of protein synthesis by binding to 30s ribosomes. Its major adverse effect is nephrotoxicity and ototoxicity

Aminoglycoside bind to 30s subunit of ribosome causing misreading of mRNA

Tetracyclines inhibit 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.

Chloramphenicol binds to the 50s subunit and inhibits peptidyl transferase

Clindamycin binds to the 50s ribosomal subunit of bacteria and disrupts protein synthesis by interfering with the transpeptidation reaction, which thereby inhibits early chain elongation.

Functional residual capacity (FRC) is 1.7 to 3.5L/kg

A capacity is the sum of two or more volumes. The total lung capacity (TLC) is total sum of the volume of gas present in all lung compartments upon maximum inspiration. It is represented mathematically as:

Total lung capacity (TLC) = Vital capacity (VC) + Residual volume (RV)

The residual volume (RV) is the volume of gas still present within the lung post maximum exhalation. It cannot be measured by spirometry, but can be using a body plethysmograph and also with the helium dilution technique.

Closing capacity (CC) is the volume of gas within the lungs at which small airways close upon expiration. It increases with age and is especially important when it surpasses the FRC as it causes changes in ventilation/perfusion mismatch and hypoxia.
In the supine position, a patient with a normal body mass index and no history of lung pathology, the CC equals the FRC at approximately 44, and at approximately 66 at standing position.

Approximately 25% of phase-1 drug reactions is made responsible by CYP2D6.

As much as a 1,000-fold difference in the ability to metabolise drugs by CYP2D6 can happen between phenotypes, and this may result in adverse drug reactions (ADRs).

The metabolism of antiemetics, beta-blockers, codeine, tramadol, oxycodone, hydrocodone, tamoxifen, antidepressants, neuroleptics, and antiarrhythmics is also as a result of CYP2D6.

Patients who take drugs that are metabolised by CYP2D6 but have poor CYP2D6 metabolism are more likely to have ADRs. People with ultra-rapid CYP2D6 metabolism may have a decreased drug effect due to low plasma concentrations of these drugs.

All the other CYP enzymes are subject to genetic polymorphism. Variants are less likely to lead to adverse drug reactions.

The renal effects of atrial natriuretic peptide (ANP) secretion are as follows:

Increased glomerular filtration rate by dilating the afferent glomerular arteriole. Moreover, it constricts the efferent glomerular arteriole, and relaxes the mesangial cells.
Reduces sodium reabsorption in the collecting ducts and distal convoluted tubule.
The renin-angiotensin system (RAS) is inhibited.
Blood flow in the vasa recta is increased.

Because plasma osmolality is unlikely to change, hypothalamic osmoreceptors are unaffected.

The plasma protein has a molecular weight of 66 kDa, is not normally filtered into the proximal convoluted tubule, and has no osmotic diuretic effect.

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 plasma and three-quarters interstitial fluid make up ECF (ISF)
The volume receptors in the atria have a 7-10% blood volume change threshold.
The osmoreceptors are sensitive to changes in osmolality of 1-2 percent.
The normal plasma osmolality before the transfusion is 287-290 mOsm/kg.
The plasma protein solution is a colloid that is only delivered to the intravascular compartment. The tonicity remains unchanged.
The blood volume increases by 20%, from 5,000 mls to 6,000 mls. This is higher than the volume receptor threshold of 7 to 10%.

The lesser omentum will need to be divided. This forms one of the nodal stations that will need to be taken during a radical gastrectomy.

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

Sugammadex is a modified cyclodextrin that works as an aminosteroid neuromuscular blocking (nmb) reversal agent. By encapsulating each molecule in the plasma, it rapidly reverses rocuronium and, to a lesser extent, vecuronium-induced neuromuscular blockade. Consequently, a  concentration gradient favours the movement of these nmb agents away from the neuromuscular junction.  Pancuronium-induced neuromuscular blockade at low levels has also been reversed.

By inhibiting voltage-dependent calcium channels at the neuromuscular junction, antibiotics in the aminoglycoside group potentiate neuromuscular blocking agents. This can be reversed by giving calcium but not neostigmine or sugammadex.

Sugammadex will not reverse the effects of mivacurium, which belongs to the benzylisoquinolinium class of drugs.

A phase II or desensitisation block occurs when the motor end-plate becomes less sensitive to acetylcholine as a result of an overdose or repeated administration of suxamethonium. The use of neostigmine has been shown to be effective in reversing this weakness.

This patient is morbidly obese and has a high risk of developing hypoxia. This will be exacerbated by the patient’s supine position, as a result of:

Functional residual capacity has been reduced (FRC)
Increased closing capacity (CC)
Reduced tidal volume due to increased airway resistance, decreased thoracic cage compliance, and decreased respiratory muscle strength and endurance
Following induction of general anaesthesia, there is a tendency for atelectasis and increased O2 consumption due to the increased workload of respiratory muscles and the overall increase in metabolism.

Pre-oxygenation with 100 percent oxygen via a tight-fitting mask can be done using either tidal volume breaths for three to five minutes or four vital capacity breaths in normal circumstances. In the head-up position, this patient is much more likely to be adequately pre-oxygenated, maximising the FRC and minimising the CC. In spontaneously breathing patients, the Mapleson A and circle systems are both effective, but the Mapleson D requires 160-200 ml/kg/minute to prevent rebreathing.

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

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

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

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

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

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

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

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

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

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

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.

Even though aprotinin reduces fibrinolysis and therefore bleeding, there is an associated increased risk of death. It was withdrawn in 2007.
Protein C is dependent upon vitamin K and this may paradoxically increase the risk of thrombosis during the early phases of warfarin treatment.

The coagulation cascade include two pathways which lead to fibrin formation:
1. Intrinsic pathway – these components are already present in the blood
Minor role in clotting
Subendothelial damage e.g. collagen
Formation of the primary complex on collagen by high-molecular-weight kininogen (HMWK), prekallikrein, and Factor 12
Prekallikrein is converted to kallikrein and Factor 12 becomes activated
Factor 12 activates Factor 11
Factor 11 activates Factor 9, which with its co-factor Factor 8a form the tenase complex which activates Factor 10

2. Extrinsic pathway – needs tissue factor that is released by damaged tissue)
In tissue damage:
Factor 7 binds to Tissue factor – this complex activates Factor 9
Activated Factor 9 works with Factor 8 to activate Factor 10

3. Common pathway
Activated Factor 10 causes the conversion of prothrombin to thrombin and this hydrolyses fibrinogen peptide bonds to form fibrin. It also activates factor 8 to form links between fibrin molecules.

4. Fibrinolysis
Plasminogen is converted to plasmin to facilitate clot resorption

Normal distribution, also called Gaussian distribution, the most common distribution function for independent, randomly generated variables, and describes the spread for many biological and clinical measurements.

Properties of the Normal distribution

symmetrical i.e. Mean = mode = median

68.3% of values lie within 1 SD of the mean

95.4% of values lie within 2 SD of the mean

99.7% of values lie within 3 SD of the mean

The empirical rule, or the 68-95-99.7 rule, tells you where most of the values lie in a normal distribution: Around 68% of values are within 1 standard deviation of the mean.

Around 95% of values are within 2 standard deviations of the mean. Around 99.7% of values are within 3 standard deviations of the mean.
the standard deviation (SD) is a measure of how much dispersion exists from the mean.

SD = square root (variance)

The empirical rule, or the 68-95-99.7 rule states where most of the values lie in a normal distribution. Around 68% of values fall within 1 S.D of the mean, about 95% within 2 S.D of the mean, and about 99.7% of values within 3 S.D of the mean. Therefore, 95.4% is the most reasonable answer if results are normally distributed.

Atrial natriuretic peptide (ANP) is secreted mainly from myocytes of right atrium and ventricle in response to increased blood volume.
It is secreted by both the right and left atria (right >> left).

It is a 28 amino acid peptide hormone, which acts via cGMP
degraded by endopeptidases.

It serves to promote the excretion of sodium, lowers blood pressure, and antagonise the actions of angiotensin II and aldosterone.

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

The spinal cord and the vertebral canal are as long as each other in early fetal life. The length of the cord increases faster than the growth of the vertebrae during development. By the time of birth, the spinal cord is at the level of the lower border of the 3rd lumbar vertebra, compared to its original position at the level of the 2nd coccygeal vertebra.

The structures that pass through the foramen magnum are:

Meningeal lymphatics
Spinal cord
Spinal meninges
Sympathetic plexus of vertebral arteries
Vertebral arteries
Vertebral artery spinal branches
The spinal roots of the accessory nerve.

The jugular foramen contains the vagus nerve, the accessory nerve and glossopharyngeal nerve.

The vertebral veins does not pass into the skull.

The Glasgow Coma Scale (GCS) has been used in outcome models as a measure of physiological derangement and as a tool for assessing head trauma.

Eye opening (E):

4 Spontaneously
3 Responds to voice
2 Responds to painful stimulus
1 No response.

Best verbal response (V):

5 Orientated, converses normally
4 Confused, disoriented conversation, but able to answer basic questions
3 Inappropriate responses, words discernible
2 Incomprehensible speech
1 Makes no sounds.

Best motor response (M):

6 Obeys commands for movement
5 Purposeful movement to painful stimulus
4 Withdraws from pain
3 Abnormal (spastic) flexor response to painful stimuli, decorticate posture
2 Extensor response to painful stimuli, decerebrate posture
1 No response.

In this case, GCS = 2+3+5 = 10.

According to European Group protocol for the investigation of MH susceptibility, muscle biopsy should be performed on quadriceps muscle (either vastus medialis or vastus lateralis), using regional anaesthesia (avoiding local anaesthetic infiltration) or general anaesthetic techniques. Local anaesthetic solution within muscle fibres may affect in vitro contraction testing.

Desflurane is a weak triggering anaesthetic of malignant hyperthermia so is avoided in MH susceptible patients. This includes all volatile inhalational agents and suxamethonium.

General anaesthetic with the volatile free anaesthetic machine may be considered but spinal anaesthesia is a better choice due to the possibility of airway problems.

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.

Bucks fascia refers to the layer of loose connective tissue, nerves and blood vessels that encapsulates the penile erectile bodies, the corpa cavernosa and the anterior part of the urethra, including the entirety of the spongiose part of the urethra.

It runs with the external spermatic fascia and the penile suspensory ligament.