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

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

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.

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

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

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

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

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

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

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

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

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

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

The first line of defence against acid-base disorder is buffering. The blood mainly utilizes bicarbonate ion (HCO3-) for its buffering capacity (total of 53%, plasma and red blood cells combined).

Strong acids, when acted upon by a buffer, release H+, which then combines to HCO3- and forms carbonic acid (H2CO3). When acted upon by the enzyme carbonic anhydrase, H2CO3 dissociates into H2O and CO.

The rest are the percentage of utilization for the following buffers:
Haemoglobin (by RBCs) – 35%
Plasma proteins (by plasma) – 7%
Organic phosphates (by RBCs) – 3%
Inorganic phosphates (by plasma) – 2%

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

Based on the presenting symptoms, this is the case of bacterial meningitis. The treatment of choice for bacterial meningitis is a cephalosporin. Cephalosporin acts by inhibiting bacterial cell wall synthesis.

The central venous pressure (CVP) waveform depicts changes of pressure within the right atrium. Different parts of the waveform are:

A wave: which represents atrial contraction. It is synonymous with the P wave seen during an ECG. It is often eliminated in the presence of atrial fibrillation, and increased tricuspid stenosis, pulmonary stenosis and pulmonary hypertension.

C wave: which represents right ventricle contraction at the point where the tricuspid valve bulges into the right atrium. It is synonymous with the QRS complex seen on ECG.

X descent: which represents relaxation of the atrial diastole and a decrease in atrial pressure, due to the downward movement of the right ventricle as it contracts. It is synonymous with the point before the T wave on ECG.

V wave: which represents an increase in atrial pressure just before the opening of the tricuspid valve. It is synonymous with the point after the T wave on ECG. It is increased in the background of a tricuspid regurgitation.

Y descent: which represents the emptying of the atrium as the tricuspid valve opens to allow for blood flow into the ventricle in early diastole.

Canon waves: which refer to large waves present on the trace that do not correspond to the A, V or C waves. They usually occur in a background of complete heart blocks or junctional arrythmias.

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

Pituitary tumours that compress the optic chiasma primarily affect the neurones that decussate at this location. Bitemporal hemianopia is caused by neurones that emerge from the nasal half of the retina and transmit the temporal half of the visual field.

The axons of ganglion cells in the retina form the optic nerve.

It exits the orbit through the optic foramen and projects to the thalamic lateral geniculate body. The optic chiasma forms above the sella turcica as the nasal fibres decussate along the way. The optic radiation travels from the lateral geniculate body to the occipital cortex.

Lesions at various points along this pathway cause the following visual field defects:

Scotoma implies partial retinal or optic nerve damage.
Monocular vision loss occurs when the optic nerve is completely damaged.
Pathology at the optic chiasma causes bitemporal hemianopia.
Cortical blindness with occipital cortex pathology and homonymous hemianopia with lesions compromising the optic radiation.

The relationship between bacterial growth and time is a tear-away exponential. The mathematical relationship between y and x in this case is:

y = ex

Where: the power is x, and the base is e.

Euler’s number (e) is a mathematical constant that is the base for all logarithms occurring naturally. Its value is 2.718.

The statement X increasing with an increase in Y is proportional to Y refers to the change in y in terms of x when considering any exponential relationship.

This is not a build-up exponential, and that is mathematically stated as y = 1-e-kt.

The negative x axis being a horizontal asymptote and the y intercept being 0, 1 are examples of tearaway exponentials , but do not describe an exponential process.

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

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

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

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

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

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 cephalic vein is a superficial vein that runs through the forearm and the arm, before draining into the axillary vein where it terminates.

Number needed to harm are a measure of the impact of a treatment or intervention that is often used to communicate results to patients, clinicians, the public and policymakers. It states how many patients need to be treated for one additional patient to experience an adverse outcome (e.g. a death). It is calculated as the inverse of the absolute risk reduction. It can equally well be applied to harmful outcomes as well as beneficial ones, where it becomes numbers needed to treat (NNT) instead.

In this way, they are both calculated the same but NNT usually refers to a therapeutic treatment whereas NNH refers to a risk-factor for disease.

Bilirubin is formed by metabolizing heme, mostly from haemoglobin in red blood cells.

Bilirubin is conjugated to glucuronic acid in the hepatocytes by the glucuronyl transferase enzyme in order to enable it to become soluble and allow for its secretion across the canalicular membrane and into bile.

The conjugation process is increased by rifampicin and decreased by valproate.

Gilbert’s syndrome is caused by a decrease in glucuronyl transferase in the hepatic system, decreasing the transport of bilirubin into the hepatocyte, causing unconjugated bilirubinaemia.

Crigler-Najjer syndrome is caused by mutations in the genes responsible for hepatic glucuronyl transferase, decreasing the activity of the enzyme, meaning bilirubin cannot be conjugated, causing unconjugated bilirubinaemia.

Dubin-Johnson syndrome does not cause an impairment in the conjugation of bilirubin, but it blocks the transport of bilirubin out of the hepatocyte resulting in conjugated bilirubinaemia.

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

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

There are 4 main pulse points for the lower limb:

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

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

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

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

The external iliac artery is the larger of the two branches of the common iliac artery. It forms the main blood supply to the lower limbs. The common iliac bifurcates into the internal and external iliac artery anterior to the sacroiliac joint.

The external iliac artery courses on the medial border of the psoas major muscles and exits the pelvic girdle posterior to the inguinal ligament. Here, midway between the anterior superior iliac spine and the pubic symphysis, the external iliac artery becomes the femoral artery and descends along the anteromedial part of the thigh in the femoral triangle.

The pectineus forms the posterior border of the femoral canal.
The femoral vein forms the lateral border of the femoral canal.
The medial border of the adductor longus muscle forms the medial wall of the femoral triangle.
The medial border of the sartorius muscle forms the lateral wall of the femoral triangle.

Rifampicin is a derivative of a rifamycin (other derivatives are rifabutin and rifapentine). It is bactericidal against both dividing and non-dividing mycobacterium and acts by inhibiting DNA-dependent RNA polymerase. Thus this drug inhibits RNA synthesis.

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

Due to an increased tidal volume with little change or slight increase in respiratory rate, Minute ventilation at term is increased by about 50%. Hypothalamic function are thought to influence by Progesterone, oestradiol and prostaglandins. This causes a mild compensated respiratory alkalosis.

Maternal PaCO2 is usually decreased to about 32 mmHg (4.27 kPa) as a result of this increased alveolar ventilation at term . A compensatory decrease in serum bicarbonate from 27 to 21 mmol/L by renal excretion lessens the impact of maternal alkalosis.

A thermocouple, or a thermal junction, is temperature measuring device consisting of a pair of dissimilar metal (bimetallic) wires or strips joined together. Typically, copper and constantan (an alloy of 55% copper and 45% nickel) are used. When there is contact between these metals, a small voltage is generated in the order of millivolts. The magnitude of the thermojunction electromotive force (emf) is proportional to applied temperature (the Seebeck effect). This physical principle is applied in the measurement of temperature. The electromotive force at the measuring junction is proportional to temperature.

Two wires with different coefficients of expansion, joined together, can be used as a switch for thermostatic control.

Semiconductors are NOT used in thermocouple. The resistance of the measuring junction of a thermocouple is irrelevant.

The cardiac action potential has several phases which have different mechanisms of action as seen below:
Phase 0: Rapid depolarisation – caused by a rapid sodium influx.
These channels automatically deactivate after a few ms

Phase 1: caused by early repolarisation and an efflux of potassium.

Phase 2: Plateau – caused by a slow influx of calcium.

Phase 3 – Final repolarisation – caused by an efflux of potassium.

Phase 4 – Restoration of ionic concentrations – The resting potential is restored by Na+/K+ATPase.
There is slow entry of Na+into the cell which decreases the potential difference until the threshold potential is reached. This then triggers a new action potential

Of note, cardiac muscle remains contracted 10-15 times longer than skeletal muscle.

Different sites have different conduction velocities:
1. Atrial conduction – Spreads along ordinary atrial myocardial fibres at 1 m/sec

2. AV node conduction – 0.05 m/sec

3. Ventricular conduction – Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec, the fastest conduction in the heart. This allows a rapid and coordinated contraction of the ventricles

Sodium-chloride symporter inhibitor.

The thiazide sensitive sodium chloride symporter is inhibited by thiazides at the proximal portion of the distal convoluted tubule leading to increased sodium and water excretion. Increased delivery of sodium to the distal portion of the distal convoluted tubule promotes potassium loss. This is why thiazides are associated with hyponatraemia and hypokalaemia.

Carbonic anhydrase inhibitors are used mainly in the treatment of glaucoma. They act on the proximal convoluted tubule to promote bicarbonate, sodium and potassium loss.

Sodium potassium chloride symporter is inhibited by Loop diuretics.
Epithelial sodium channels are inhibited by Amiloride.
Drugs which lead to nephrogenic diabetes insipidus such as lithium and demeclocycline, are Inhibitors of vasopressin.

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 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.

From superior to inferior, the following structures enter the orbit through the superior orbital fissure:
1. Lacrimal nerve
2. Frontal nerve
3. Superior ophthalmic vein
4. Trochlear nerve
5. Superior division of the oculomotor nerve*
6. Nasociliary nerve*
7. Inferior division of the oculomotor nerve*
8. Abducent nerve*
9. Inferior ophthalmic vein.

The superior and inferior division of the oculomotor nerve, nasociliary nerve, and abducent nerve are within the tendinous ring.

The common origin of the four rectus muscles is the tendinous ring (also known as the annulus of Zinn). The tendinous ring’s lateral portion straddles the superior orbital fissure, while the medial portion encloses the optic foramen, through which the optic nerve and ophthalmic artery pass.

The needle should be inserted just below the skin at the mid inguinal point which is the surface indicator for the femoral artery.

The toxicity of organophosphorus (OP) nerve agents is manifested through irreversible inhibition of acetylcholinesterase (AChE) at the cholinergic synapses, which stops nerve signal transmission, resulting in a cholinergic crisis and eventually death of the poisoned person. Oxime compounds used in nerve agent antidote regimen reactivate nerve agent-inhibited AChE and halt the development of this cholinergic crisis.