Bone pain, pathologic fractures, weakness, anaemia, infection, hypercalcemia, spinal cord compression, and renal failure are all signs and symptoms of multiple myeloma (MM). The patient’s condition matched the signs and symptoms of myeloma.

About 80% of bicarbonate is reabsorbed in the proximal tubule. HCO3-is not transported directly, tubular HCO3-associates with H+secreted by epithelial Na+/H+antiporters to form carbonic acid (H2CO3) which readily dissociates to form carbon dioxide and water in the presence of carbonic anhydrase. CO2and water diffuse into the tubular cells, where they recombine to form carbonic acid which dissociates to H+and HCO3-. This HCO3-is transported into the interstitium largely by Na+/HCO3-symporters on the basolateral membrane (and H+is secreted back into the lumen). For each H+secreted into the lumen, one Na+and one HCO3-are reabsorbed into the plasma. H+is recycled so there is little net secretion of H+at this stage.

Infection of the genital mucosa by Neisseria gonorrhoeae involves attachment to and invasion of epithelial cells. Initial adherence of gonococci to columnar epithelial cells is mediated by type IV pili assembled from pilin subunit PilE proteins and pilus tip-associated PilC proteins, it then invades the epithelial layer, triggering a local acute inflammatory response.

Febrile transfusion reactions presents with an unexpected temperature rise (≥ 38ºC or ≥ 1ºC above baseline, if baseline ≥ 37ºC) during or shortly after transfusion. It is usually an isolated finding and the fever is accompanied by chills and malaise occasionally.

Allergic reaction is commonly caused by foreign plasma proteins but may be due to anti-IgA. Allergic type reactions usually present with urticaria, pruritus, hives. Associations include laryngeal oedema or bronchospasm.

Acute haemolytic reaction aka immediate haemolytic transfusion reaction presents with fever, chills, pain at transfusion site, nausea, vomiting, dark urine and feeling of ‘impending doom’. Often, it occurs due to ABO incompatibility.

Transfusion-associated circulatory overload (TACO) presents as acute or worsening respiratory distress within 6 hours of transfusion of a large volume of blood. It is common in patients with diminished cardiac reserve or chronic anaemia. Elderly patients, infants and severely anaemic patients are particularly susceptible. Clinical features of TACO include: Acute respiratory distress, Tachycardia, Hypertension, Acute/worsening pulmonary oedema on chest X-ray. The BNP is usually raised to at least 1.5 times the pre-transfusion baseline.

Transfusion-related lung injury (TRALI) is a form of acute respiratory distress caused by the donor plasma containing antibodies against the patient’s leukocytes. It is defined as hypoxia and bilateral pulmonary oedema that occurs within 6 hours of a transfusion in the absence of other causes of acute lung injury. Clinical features include Breathlessness, cough, frothy sputum, hypertension or hypotension, hypoxia and fever. Chest X-ray shows multiple perihilar nodules with infiltration of the lower lung fields.

A median nerve block is a simple, safe, and effective method of obtaining anaesthesia to the palmar aspect of the thumb, index finger, middle finger, radial portion of the palm and ring finger. The median nerve lies deep to the flexor retinaculum and about one centimetre under the skin of the volar wrist.
The palmaris longus tendon lies superficial to the retinaculum and is absent in up to 20% of patients.
The median nerve is located slightly lateral (radial) to the palmaris longus tendon and medial (ulnar) to the flexor carpi radialis tendon.

The procedure is as follows:
– Check sensation and motor function of the median nerve. Wear gloves and use appropriate barrier precautions.
– Locate the flexor carpi radialis and palmaris longus tendons, which become prominent when the patient flexes the wrist against resistance. The palmaris longus tendon is usually the more prominent of the two tendons.
– Needle-entry site: The needle will be inserted adjacent to the radial (lateral) border of the palmaris longus tendon just proximal to the proximal wrist crease. If the palmaris longus tendon is absent, the needle-entry site is about 1 cm ulnar to the flexor carpi radialis tendon.
– Cleanse the site with antiseptic solution. Place a skin wheal of anaesthetic, if one is being used, at the needle-entry site.
– Insert the needle perpendicularly through the skin and advance it slowly until a slight pop is felt as the needle penetrates the flexor retinaculum. When paraesthesia in the distribution of the median nerve confirms proper needle placement, withdraw the needle 1 to 2 mm.
– Aspirate to exclude intravascular placement and then slowly (i.e., over 30 to 60 seconds) inject about 3 mL of anaesthetic. If the patient does not feel paraesthesia, redirect the needle in an ulnar direction, under the palmaris longus tendon. If paraesthesia is still not felt, slowly inject 3 to 5 mL of anaesthetic in the proximity of the nerve 1 cm deep to the tendon.
– Allow about 5 to 10 minutes for the anaesthetic to take effect.

Amiodarone is an anti-arrhythmic medication that can be used to treat both ventricular and atrial arrhythmias.

The use of amiodarone is contraindicated in the following situations:
Conduction disturbances that are severe (unless pacemaker fitted)
Sinus node disease is a condition that affects the lymph nodes in (unless pacemaker fitted)
Sensitivity to iodine
Blockage of the Sino-atrial heart valve (except in cardiac arrest)
Bradycardia in the sinuses (except in cardiac arrest)
Thyroid disorders

Features include:
– severe anaemia (becoming apparent at 3 – 6 months when the switch from gamma-chain to beta-chain production takes place)
– failure to thrive
– hepatosplenomegaly (due to excessive red cell destruction, extramedullary haemopoiesis and later due to transfusion related iron overload)
– expansion of bones (due to marrow hyperplasia, resulting in bossing of the skull and cortical thinning with tendency to fracture)
– increased susceptibility to infections (due to anaemia, iron overload, transfusion and splenectomy)
– osteoporosis
– hyperbilirubinaemia and gallstones
– hyperuricaemia and gout
– other features of haemolytic anaemia
– liver damage and other features of iron overload

Damage to the superficial fibular nerve results in loss of eversion of the foot and loss of sensation over the lower anterolateral leg and the dorsum of the foot.

Pabrinex is indicated in patients that require rapid therapy for severe depletion or malabsorption of water-soluble vitamins B and C, particularly in alcoholism detoxification.

Pabrinex has the following:
1. Thiamine (vitamin B1)
2. Riboflavin (vitamin B2)
3. Nicotinamide (Vitamin B3, niacin and nicotinic acid)
4. Pyridoxine (vitamin B6)
5. Ascorbic acid (vitamin C)
6. Glucose

Suspected or established Wernicke’s encephalopathy is treated by intravenous infusion of Pabrinex/ The dose is 2-3 pairs three times a day for three to five days, followed by one pair once daily for an additional three to five days or for as long as improvement continues.

Receiver-operating characteristic (ROC) analysis was originally developed during World War II to analyse classification accuracy in differentiating signal from noise in radar detection. Recently, the methodology has been adapted to several clinical areas heavily dependent on screening and diagnostic tests, in particular, laboratory testing, epidemiology, radiology, and bioinformatics. ROC analysis is a useful tool for evaluating the performance of diagnostic tests and more generally for evaluating the accuracy of a statistical model (e.g., logistic regression, linear discriminant analysis) that classifies subjects into 1 of 2 categories, diseased or non diseased. Its function as a simple graphical tool for displaying the accuracy of a medical diagnostic test is one of the most well-known applications of ROC curve analysis.

The closer the ROC curve is to the upper left corner, which has 100% sensitivity and 100% specificity, the higher the overall accuracy of the diagnostic test.

Barbiturates induce hepatic enzymes. The enzyme gamma aminolevulinic acid synthetase, which produces porphyrins, can be induced and in susceptible patients an attack of acute intermittent porphyria can occur. Thiopental is absolutely contraindicated in these patients.

Dobutamine is a synthetic isoprenaline derivative that is used to provide inotropic support to patients with low cardiac output caused by septic shock, myocardial infarction, or other cardiac conditions.

Dobutamine is a sympathomimetic drug that stimulates beta-1 adrenergic receptors in the heart to produce its primary effect. As a result, it has inotropic properties that increase cardiac contractility and output. It also has a small amount of alpha1- and beta-2-adrenergic activity.

It is infused intravenously after being diluted to a volume of at least 50 ml in a suitable crystalloid solution. The dose is titrated to response and ranges from 0.5 to 40 g/kg/min. Extravasation-induced skin necrosis is uncommon, and dobutamine can be administered through a peripheral line.

At doses below 10 g/kg/min, side effects are rare, but at higher doses, they can include:
Nausea and vomiting
Tachycardia
Dysrhythmias
Angina
Hypertension
Headache

When there are excessive levels of aldosterone independent of the renin-angiotensin aldosterone axis, primary hyperaldosteronism occurs. Secondary hyperaldosteronism occurs due to high renin levels.

Causes of primary hyperaldosteronism include:
Conn’s syndrome
Adrenal hyperplasia
Adrenal cancer
Familial aldosteronism

Causes of secondary hyperaldosteronism include:
Renal vasoconstriction
Oedematous disorders
Drugs – diuretics
Obstructive renal artery disease

Although patients are usually asymptomatic, when clinical features are present, classically hyperaldosteronism presents with:
Hypokalaemia
Sodium levels can be normal or slightly raised
Hypertension
Metabolic alkalosis
Less common, clinical features are:
Lethargy
Headaches
Intermittent paraesthesia
Polyuria and polydipsia
Muscle weakness (from persistent hypokalaemia)
Tetany and paralysis (rare)

Angiotensin II constricts both the afferent and efferent arterioles, but preferentially increases efferent resistance. The net effect of the more prominent increase in efferent tone is that the intraglomerular pressure is stable or increased, thereby tending to maintain or even raise the GFR. Renin is produced by granular cells of the juxtaglomerular apparatus. Renin cleaves plasma angiotensinogen (produced in the liver) into angiotensin I. Angiotensin I is converted by angiotensin-converting enzyme (ACE) on pulmonary endothelial cells to angiotensin II. Angiotensin II acts to potentiate sympathetic activity (positive feedback).

Frictional forces at the sides of a vessel cause a drag force on the fluid touching them in laminar blood flow, which creates a velocity gradient where the flow is greatest at the centre. Laminar blood flow may become disrupted and flow may become turbulent at high velocities, especially in large arteries or where the velocity increases sharply at points of sudden narrowing in the vessels, or across valves. There is increased tendency for thrombi formation when there is turbulent blood flow. Clinically, turbulence may be heard as a murmur or a bruit. As a result of elevated cardiac output, there may be turbulent blood flow, even when the cardiac valves are anatomically normal, and as a result, a physiological murmur can be heard. One such example is pregnancy.

Flow through a tube is dependent upon:
The pressure difference across the ends of the tube (P1– P2)
The resistance to flow provided by the tube (R)
This is Darcy’s law, which is analogous to Ohm’s law in electronics:
Flow = (P1– P2) / R
Resistance in the tube is defined by Poiseuille’s law, which is determined by the diameter of the tube and the viscosity of the fluid. Poiseuille’s law is as follows:
Resistance = (8VL) / (πR4)
Where:
V = The viscosity of the fluid
L = The length of the tube
R = The radius of the tube
Therefore, in simple terms, resistance is directly proportional to the viscosity of the fluid and the length of the tube and inversely proportional to the radius of the tube. Of these three factors, the most important quantitatively and physiologically is vessel radius.
It can be seen that small changes in the radius can have a dramatic effect on the flow of the fluid. For example, the constriction of an artery by 20% will decrease the flow by approximately 60%.
Another important and frequently quoted example of this inverse relationship is that of the radius of an intravenous cannula. Doubling the diameter of a cannula increases the flow rate by 16-fold (r4). This is the reason the diameter of an intravenous cannula in resuscitation scenarios is so important.
*Please note that knowledge of the detail of Poiseuille’s law is not a requirement of the RCEM Basic Sciences Curriculum.

A prodromal 2 – 4 day coryzal illness (fever, cough, conjunctivitis, irritability) normally occurs associated with Koplik’s spots (small white papules found on the buccal mucosa near the first premolars), before a morbilliform maculopapular rash appears, first behind the ears and then spreading downwards to whole body.The rash peels off or fades about about 7 – 10 days. The chickenpox rash is characterised by a maculopapular rash progressing to vesicles and then crusting over. Scarlet fever is characterised by a sandpaper like rash associated with a strawberry tongue.

ADH binds V2 receptors on renal principal cells in the late distal tubule and collecting ducts, raising cAMP levels and causing intracellular vesicles to fuse with the apical membrane. In their membrane these vesicles have water channels called aquaporins, which increase the water permeability allowing greater water reabsorption and concentration of urine. ADH also binds to V1 receptor receptors on vascular smooth muscle, causing vasoconstriction and enhancing the effect of aldosterone on sodium reabsorption in the distal tubule. ADH release is stimulated primarily by raised plasma osmolality detected by osmoreceptors in the anterior hypothalamus. Other factors that increase ADH release include: extracellular fluid volume depletion, angiotensin II, nausea, pain, stress, exercise, emotion, hypoglycaemia. ADH release is inhibited by low plasma osmolality, alcohol, caffeine, glucocorticoids and atrial natriuretic peptide (ANP). ADH deficiency (or an inadequate response to ADH) results in diabetes insipidus. Excess levels of ADH results in syndrome of inappropriate ADH secretion (SIADH).

There are three types of muscle:
Skeletal muscle
Cardiac muscle
Smooth muscle

Individual muscle is enveloped in a layer of dense irregular connective tissue called the epimysium. The epimysium protects the muscles from friction against bones and other muscles.

Skeletal muscle is composed of muscle fibres, referred to as myofibers which is ensheathed by a wispy layer of areolar connective tissue called the endomysium. The endomysium is the smallest and deepest component of muscle connective tissue.

Myofibers grouped together in bundles form fascicles, or fasciculi. These are surrounded by a type of connective tissue called the perimysium.

Beneath the endomysium lies the sarcolemma, an elastic sheath with infoldings that invaginate the interior of the myofibers, particularly at the motor endplate of the neuromuscular junction.

Cardiac myocytes contract by excitation-contraction coupling, just like skeletal myocytes. Heart myocytes, on the other hand, utilise a calcium-induced calcium release mechanism that is unique to cardiac muscle (CICR). The influx of calcium ions (Ca2+) into the cell causes a ‘calcium spark,’ which causes more ions to be released into the cytoplasm.

An influx of sodium ions induces an initial depolarisation, much as it does in skeletal muscle; however, in cardiac muscle, the inflow of Ca2+ sustains the depolarisation, allowing it to remain longer. Due to potassium ion (K+) inflow, CICR causes a plateau phase in which the cells remain depolarized for a short time before repolarizing. Skeletal muscle, on the other hand, repolarizes almost instantly.

The release of Ca2+ from the sarcoplasmic reticulum is required for calcium-induced calcium release (CICR). This is mostly accomplished by ryanodine receptors (RyR) on the sarcoplasmic reticulum membrane; Ca2+ binds to RyR, causing additional Ca2+ to be released.

The meningococcus is solely a human pathogen, and up to 50% of the population may carry meningococci in the nasopharynx. Factors that lead to invasion and production of disease include complex inter-relationships of genetic predisposition, host status, environmental conditions, and virulence of the organism.

Meningococcal disease is the most common infectious cause of death in childhood in developed countries. It presents as septicaemia, meningitis, or a combination. Septicaemia is the more dangerous presentation, especially with septic shock; meningitis is more likely to lead to neurodevelopmental sequelae. Classic features of septicaemia are a non-blanching rash in a feverish, ill child.

Hypothyroidism occurs when there is a deficiency of circulating thyroid hormones. It is commoner in women and is most frequently seen in the age over 60.

Iodine deficiency is the commonest cause of hypothyroidism worldwide.

In developed countries, iodine deficiency is not a problem and autoimmune thyroiditis is the commonest cause.

Parathyroid hormone (PTH) is a peptide hormone synthesised by the chief cells of the parathyroid glands, located immediately behind the thyroid gland. PTH is primarily released in response to decreasing plasma [Ca2+] concentration. PTH acts to increase plasma calcium levels and decrease plasma phosphate levels.
Parathyroid hormone (PTH) acts to increase calcium reabsorption in the distal tubule of the nephron (by activating Ca2+entry channels in the apical membrane and the Ca2+ATPase pump in the basolateral membrane) and increase phosphate excretion by inhibiting reabsorption in the proximal tubule of the nephron.

Somatostatin-producing cells present in the pyloric antrum, duodenum, and pancreatic islets are known as D-cells or delta-cells. Somatostatin inhibits gastric acid secretion by acting directly on acid-producing parietal cells in the stomach via a G-protein coupled receptor.

Somatostatin affects hormones in the following ways:
Inhibits the anterior pituitary’s secretion of growth hormone.
Inhibits the anterior pituitary’s secretion of thyroid-stimulating hormone.

The secretion of various gastrointestinal hormones is inhibited (including gastrin, CCK, secretin, motilin, VIP and GIP)

Reduces the rate at which the stomach empties.
Inhibits the release of insulin and glucagon from the pancreas.

The pancreas’ exocrine secretory activity is inhibited.
Somatostatin can also slow the digestive process by suppressing the production of hormones such gastrin, secretin, and histamine, which reduces gastric acid secretion.

A somatostatinoma is a cancerous tumour of the endocrine pancreas’ D-cells, which make somatostatin. Somatostatin inhibits pancreatic and gastrointestinal hormones when levels are high. The following clinical characteristics are related with somatostatinomas:

Insulin secretion blockage causes diabetes mellitus.
Gallstones by inhibition of CCK and secretin Steatorrhoea via inhibition of CCK and secretin

Hypochlorhydria is caused by the suppression of gastrin, a hormone that increases gastric acid output regularly.

Adverse effects include:
Drowsiness and lightheadedness
Confusion and ataxia (especially in the elderly), amnesia, muscle weakness
Headache, vertigo, tremor, dysarthria, hypotension, decreased libido, erectile dysfunction, gynaecomastia, urinary retention
Paradoxical effects such as talkativeness, excitement, irritability, aggression, anti-social behaviour, and suicidal ideation
Withdrawal symptoms, for example anxiety, depression, anorexia, impaired concentration, insomnia, abdominal cramps, palpitations, tremor, tinnitus and perceptual disturbances
Tolerance and dependence (people who use benzodiazepines longer term can develop tolerance and eventual dependence)

A scatterplot is a useful summary of a set of bivariate data (two variables), usually drawn before working out a linear correlation coefficient or fitting a regression line. It gives a good visual picture of the relationship between the two variables, and aids the interpretation of the correlation coefficient or regression model. Each unit contributes one point to the scatterplot, on which points are plotted but not joined. The resulting pattern indicates the type and strength of the relationship between the two variables.

Phenytoin is in the anticonvulsants class of drugs and is used in the management and treatment of the following:
1. epilepsy
2. generalized tonic-clonic seizures
3. complex partial seizures
4. status epilepticus.

It works by inactivating the voltage-gated sodium channels responsible for increasing the action potential. It is non-specific and targets almost all voltage-gated sodium channel subtypes. More specifically, phenytoin prevents seizures by inhibiting the positive feedback loop that results in neuronal propagation of high-frequency action potentials.

Categorical data or data that is ordered is Ordinal data e.g. disease staging system, pain scoring system.

Disease staging system is the correct answer

A posterior wall MI occurs when posterior myocardial tissue (now termed inferobasilar), usually supplied by the posterior descending artery — a branch of the right coronary artery in 80% of individuals — acutely loses blood supply due to intracoronary thrombosis in that vessel. This frequently coincides with an inferior wall MI due to the shared blood supply.

The ECG findings of an acute posterior wall MI include the following:

1. ST segment depression (not elevation) in the septal and anterior precordial leads (V1-V4). This occurs because these ECG leads will see the MI backwards; the leads are placed anteriorly, but the myocardial injury is posterior.
2. A R/S wave ratio greater than 1 in leads V1 or V2.
3. ST elevation in the posterior leads of a posterior ECG (leads V7-V9). Suspicion for a posterior MI must remain high, especially if inferior ST segment elevation is also present.
4. ST segment elevation in the inferior leads (II, III and aVF) if an inferior MI is also present.

The following ECG leads determine the location and vessels involved in myocardial infarction:

ECG Leads Location Vessel involved
V1-V2 Septal wall Left anterior descending
V3-V4 Anterior wall Left anterior descending
V5-V6 Lateral wall Left circumflex artery
II, III, aVF Inferior wall Right coronary artery (80%) or Left circumflex artery (20%)
I, aVL High lateral wall Left circumflex artery
V1, V4R Right ventricle Right coronary artery
V7-V9 Posterior wall Right coronary artery

The obturator externus is innervated by the posterior branch of the obturator nerve, L2-L4.