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.

Meningitis is defined as the inflammation of the meninges due to an infection caused by a bacteria or a virus. Symptoms usually include stiffness of the neck, headache, and fever.
There are 3 meningeal layers that surround the spinal cord and they are the dura mater, arachnoid matter, and pia mater.

The dura mater is the outermost and thickest layer out of all the 3 layers.
The arachnoid atter is the middle layer, and is very thin.
The third and deepest meningeal layer is the pia mater that is bound tightly to the surface of the spinal cord.

Acetaminophen is an acetanilide derivative and is a widely used non-prescription analgesic and antipyretic medication for mild-to-moderate pain and fever.

The route of elimination: Metabolites are mainly excreted in the urine. <5% is excreted as free (unconjugated) acetaminophen, and >90% of the dose administered is excreted within 24 hours.

It is thought to work by selectively inhibiting COX-1 receptors in the brain and spinal cord: It is categorized by the FDA as an NSAID as it is believed to selectively inhibit cyclo-oxygenase 3 (COX-3) receptors in the brain and spinal cord.

COX-3 is a unique variant of the more known COX-1 and COX-2. It is responsible for the production of prostaglandins in central areas, which sensitizes free nerve endings to the chemical mediators of pain. Therefore, by selectively inhibiting COX-3, paracetamol effectively reduces pain sensation by increasing the pain threshold.

Toxicity is primarily due to glutathione production: Acetaminophen metabolism by the CYP2E1 pathway releases a toxic metabolite known as N-acetyl-p-benzoquinoneimine (NAPQI). NAPQI primarily contributes to the toxic effects of acetaminophen. NAPQI is an intermediate metabolite that is further metabolized by fast conjugation with glutathione. The conjugated metabolite is then excreted in the urine as mercapturic acid. High doses of acetaminophen (overdoses) can lead to hepatic necrosis due to depleting glutathione and high binding levels of reactive metabolite (NAPQI) to important parts of liver cells.

It has a half-life of 6-8 hours: Acetaminophen can be administered orally, rectally, or intravenously. It is predominantly metabolized in the liver, and the elimination half-life is 1-3 hours after a therapeutic dose. But maybe greater than 12 hours after an overdose.

It is primarily metabolized via the cytochrome p450 enzyme system: It is predominantly metabolized in the liver by three main metabolic pathways:
1. Glucuronidation (45-55%)
2. Sulphate conjugation (30-35%)
3. N-hydroxylation via the hepatic cytochrome p450 enzyme system (10-15%)

Amitriptyline is a tricyclic antidepressant (TCA) that is most commonly used to treat depression, but it can also be used to treat anxiety disorders, chronic pain, and attention deficit hyperactivity disorder (ADHD). It inhibits reuptake, raising serotonin and noradrenaline levels while also inhibiting acetylcholine action.

TCAs have a number of drawbacks, including:
Acute Porphyria
Arrhythmias
During bipolar disorder’s manic phase
Heart block
After a myocardial infarction, there is an immediate recovery period.

TCA levels in breast milk are too low to be harmful, and use can be continued while breastfeeding.

According to various studies, the frequency of acute nerve damage associated with supracondylar humeral fractures in children ranges from 10% to 20%.

Median nerve injury and anterior interosseous nerve injury are the most common consequences.

Damage to this nerve indicated weakening or abnormal extension of the index finger’s distal interphalangeal joint and the thumb’s interphalangeal joint. The absence of sensibility is a distinguishing attribute.

A surgical neck humerus fracture may cause injury to the axillary nerve. A midshaft humerus fracture might cause injury to the radial nerve. A medial epicondylar fracture might cause injury to the ulnar nerve.

Herpes simplex virus is the most common cause of infective encephalitis and has a predilection for the temporal lobes. Herpes simplex is transmitted through direct contact. It invades skin locally producing skin vesicles by its cytolytic activity.

The absolute risk (AR) is the probability or chance of an event. It is computed as the number of events in treated or control groups, divided by the number of people in that group.

AR = 25/500 = 0.05

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.

Legionella pneumophilais a Gram negative bacterium that is found in natural water supplies and in the soil, transmitted predominantly via inhalation of aerosols generated from contaminated water (direct person-to-person spread of infected patients does not occur). It is the cause of Legionnaires’ disease. Outbreaks of Legionnaires’ disease have been linked to poorly maintained air conditioning systems, whirlpool spas and hot tubs.

The clinical features of the pneumonic form of Legionnaires’ disease include:
Mild flu-like prodrome for 1-3 days
Cough (usually non-productive and occurs in approximately 90%)
Pleuritic chest pain
Haemoptysis
Headache
Nausea, vomiting and diarrhoea
Anorexia
Legionella pneumophilainfections can be successfully treated with macrolide antibiotics, such as erythromycin, or quinolones, such as ciprofloxacin. Tetracyclines, such as doxycycline, can also be used.
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur with Legionnaires’ disease and will result in hyponatraemia as is seen in this case.
Legionella pneumophilainfections are resistant to amoxicillin but can be successfully treated with macrolide antibiotics, such as erythromycin, or quinolones, such as ciprofloxacin. Tetracyclines, such as doxycycline, can also be used. The majority of cases of Legionnaires’ disease are caused by Legionella pneumophila, however many other species of Legionella have been identified.
Legionella longbeachae is another less commonly encountered species that has also been implicated in outbreaks. It is predominantly found in soil and potting compost, and has caused outbreaks of Pontiac fever, the non-respiratory and less severe variant of Legionnaires’ disease.

Penicillin is bactericidal and produces its antimicrobial action by preventing cross-linkage between the linear peptidoglycan polymer chains that make up the bacterial cell wall. This action inhibits cell wall synthesis.

Phagocytosis is largely responsible for depletion of cells coated with antibodies. Cells opsonized by IgG antibodies are recognized by phagocyte Fc receptors, which are specific for the Fc portions of some IgG subclasses. In addition, when IgM or IgG antibodies are deposited on the surfaces of cells, they may activate the complement system by the classical pathway. Complement activation generates by-products, mainly C3b and C4b, which are deposited on the surfaces of the cells and recognized by phagocytes that express receptors for these proteins. The net result is phagocytosis of the opsonized cells and their destruction.

HIV mainly infects CD4+ T helper cells. Viral replication results in progressive T-cell depletion and impaired cell-mediated immunity with subsequent secondary opportunistic infections and increased risk of malignancy. B-cell function is also reduced as a result of lack of T-cell stimulation.
HIV is not a notifiable disease.

Cushing’s syndrome is a group of symptoms and signs brought on by long-term exposure to high amounts of endogenous or exogenous glucocorticoids. Cushing’s syndrome affects about 10-15 persons per million, and it is more common in those who have had a history of obesity, hypertension, or diabetes.

A typical biochemical profile can help establish a diagnosis of Cushing’s syndrome. The following are the primary characteristics:
Hypokalaemia
Alkalosis metabolique

Bacillus cereus = Gram-positive bacillus
Neisseria meningitidis = Gram-negative coccus
Salmonella enterica & Escherichia coli = Gram-negative bacilli

In Gram staining, crystal violet is a purple stain that is used to stain the bacteria first. The stained bacteria are decolorized and then stained with a red stain, which is safranin. Bacteria with thick cell walls keep the purple stain and are called Gram-positive. Thin-walled bacteria are easily decolorized so when safranin, the red stain, is placed on the organisms, they become red or Gram-negative.
The Staphylococci that are associated with infections in humans are colonizers of various skin and mucosal surfaces. Because the carrier state is common among the human population, infections are frequently acquired when the colonizing strain gains entrance to a normally sterile site as a result of trauma or abrasion to the skin or mucosal surface.

Captopril is an angiotensin-converting enzyme (ACE) inhibitor, which inhibits the conversion of angiotensin I to angiotensin II.

Lymphatic vessels from the pharynx and palate drain into the deep cervical lymph nodes.

Metoclopramide is used to treat nausea and vomiting. It works by blocking the central and peripheral D2 (dopamine 2) receptors in the medullary chemoreceptor trigger zone in the vomiting centre (area postrema). It decreases the sensitivity of the visceral sensory nerves that transmit from the GI system to the vomiting centre. Blockade of inhibitory dopamine receptors in the GI tract may allow stimulatory actions of ACh at muscarinic synapses to predominate.

At high doses, metoclopramide also blocks type-2 serotonin receptors though the effect is much weaker.

Bacterial meningitis and septicaemia are most commonly caused by meningococcal bacteria. The Gram-negative diplococci Neisseria Meningitidis causes meningitis. Gram stain and culture of CSF identify the etiologic organism, N meningitidis. In bacterial meningitis, Gram stain is positive in 70-90% of untreated cases, and culture results are positive in as many as 80% of cases.

The biceps brachii muscle is one of the chief muscles of the arm. The origin at the scapula and the insertion into the radius of the biceps brachii means it can act on both the shoulder joint and the elbow joint, which is why this muscle participates in a few movements of the arm. It derives its name from its two heads which merge in one unique distal body, defining the unusual structure of the muscle.

The biceps brachii muscle is supplied by the musculocutaneous nerve (C5-C6), a branch of the brachial plexus.

Arterial supply to the biceps brachii muscle varies considerably, coming from up to eight vessels originating from the brachial artery in the middle third of the arm.

In the shoulder joint both muscle heads partially enforce opposite movements. The long head pulls the arm away from the trunk (abduction) and turns it inwards (inward rotation) whereas the short head pulls the arm back towards the trunk (adduction). When both heads contract simultaneously it leads to an arm bend (flexion). In the elbow joint the muscle bends the forearm (flexion) and rotates it outwards (supination). The supination is most powerful in a flexed elbow. In addition to the movement functions, the biceps has the important task to support the humeral head within the shoulder joint. Its antagonist is the triceps brachii in the posterior compartment of the arm.

The vast majority of systems within the body work by negative feedback mechanisms. This negative feedback refers to the way that effectors act to move the variable in the opposite direction to the change that was originally detected. Because there is an inherent time delay between detecting a change in a variable and effecting a response, the negative feedback mechanisms cause oscillations in the variable they control. There is a narrow range of values within which a normal physiological function occurs and this is called the ‘set point’. The release of oxytocin in childbirth is an example of positive feedback.

The most common cause of upper gastrointestinal bleeding is peptic ulcer disease, particularly gastric and duodenal ulcers. Duodenal ulcers are most commonly associated with bleeding compared with gastric ulcers. Posterior duodenal ulcers are considered to be the most likely to cause severe bleeding because of its proximity to the branches of the gastroduodenal artery (GDA).

The FDA categorizes Paracetamol as an NSAID (nonsteroidal anti-inflammatory drug) as it is believed to selectively inhibit cyclo-oxygenase 3 (COX-3) receptors in the brain and spinal cord.

COX-3 is a unique variant of the more known COX-1 and COX-2. It is responsible for the production of prostaglandins in central areas, which sensitizes free nerve endings to the chemical mediators of pain. Therefore, by selectively inhibiting COX-3, paracetamol effectively reduces pain sensation by increasing the pain threshold.
Acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, therefore, has no peripheral anti-inflammatory effects.
The antipyretic actions of acetaminophen are likely attributed to direct action on heat-regulating centres in the brain, resulting in peripheral vasodilation, sweating, and loss of body heat.

Some potential symptoms of frontal lobe damage can include loss of movement, either partial or complete, on the opposite side of the body.

In the patient’s case, it is a result of motor cortex damage on the right side since her left side of the body is affected. The conjugate eye deviation symptom towards the side of the lesion is a result of damage to the frontal eye field.

Ketoacidosis is characterized by hyperglycaemia, glycosuria, hyperkalaemia, and metabolic acidosis with respiratory compensation. An insulin infusion would be able to address these by lowering blood glucose through increased insulin-mediated cellular uptake, lowering urine glucose concentration as cellular glucose uptake is increased, decreasing K+ in her blood by shifting it into cells, and increasing blood ph by addressing the metabolic acidosis. The metabolic acidosis is addressed by the reduction of ketoacids production thereby returning her blood ph to normal and reducing the need for compensatory hyperventilation.

Acute haemolytic transfusion reactions present with: Feeling of ‘impending doom’ as the earliest symptom, fever and chills, pain and warmth at transfusion site, nausea and vomiting, back, joint, and chest pain. Transfusion should be stopped immediately and IV fluid (usually normal saline) administered.

Supportive measures and paracetamol can be given since patient has fever but it is not the immediate first step.

Antimuscarinics are contraindicated in paralytic ileus. Antimuscarinics reduce intestinal motility by blocking muscarinic acetylcholine receptors and relaxing smooth muscle. Hyoscine butylbromide is advocated as a gastrointestinal antispasmodic, but it is poorly absorbed and thus has limited clinical utility. Antimuscarinics cause a reduction in bronchial secretions (they can be used to this effect in palliative patients). Antispasmodics are occasionally of value in treating abdominal cramp associated with diarrhoea but they should not be used for primary treatment. Antispasmodics should be avoided in young children with gastroenteritis because they are rarely effective and have troublesome side effects.

In an anterior dislocation, the arm is an abducted and externally rotated position. In the externally rotated position, the posterosuperior aspect of the humeral head abuts and drives through the anteroinferior aspect of the glenoid rim. This can damage the humeral head, glenoid labrum, or both. An associated humeral head compression fracture is described as a Hill Sach’s lesion. If large enough, it can lead to locked dislocations that may require open reduction. The glenoid labrum is a fibrocartilaginous structure that rings the circumference of the glenoid fossa. Bankart lesions are injuries to the anteroinferior glenoid labrum complex and the most common capsulolabral injury. A bony Bankart lesion refers to an associated fracture of the glenoid rim. These capsulolabral lesions are risk factors for recurrent dislocation.

Axillary nerve injury is identified in about 42% of acute anterior shoulder dislocations. Nerve transection is rare, and traction injuries are more common. Arterial injury has also been described. The subclavian artery becomes the axillary artery after passing the first rib. The distal portion of the axillary artery is anatomically fixed and, therefore, susceptible to injury in anterior dislocations. Ischemic injury, including pseudoaneurysm and arterial laceration, is rare but carries marked morbidity if not quickly identified.

Haemoglobin is a 64.4 kd tetramer consisting of two pairs of globin polypeptide chains: one pair of alpha-like chains, and one pair of non-alpha chains. The chains are designated by Greek letters, which are used to describe the particular haemoglobin (e.g., Hb A is alpha2/beta2).

Two copies of the alpha-globin gene (HBA2, HBA1) are located on chromosome 16 along with the embryonic zeta genes (HBZ). There is no substitute for alpha globin in the formation of any of the normal haemoglobins (Hb) following birth (e.g., Hb A, Hb A2, and Hb F). Thus, absence any alpha globin, as seen when all 4 alpha-globin genes are inactive or deleted is incompatible with extrauterine life, except when extraordinary measures are taken.

A homotetramer of only alpha-globin chains is not thought to occur, but in the absence of alpha chains, beta and gamma homotetramers (HbH and Bart’s haemoglobin, respectively) can be found, although they lack cooperativity and function poorly in oxygen transport. The single beta-globin gene (HBB) resides on chromosome 11, within a gene cluster consisting of an embryonic beta-like gene, the epsilon gene (HBE1), the duplicated and nearly identical fetal, or gamma globin genes (HBG2, HBG1), and the poorly expressed delta-globin gene (HBD). A heme group, consisting of a single molecule of protoporphyrin IX co-ordinately bound to a single ferrous (Fe2+) ion, is linked covalently at a specific site to each globin chain. If the iron is oxidized to the ferric state (Fe3+), the protein is called methaemoglobin.

Alpha globin chains contain 141 amino acids (residues) while the beta-like chains contain 146 amino acids. Approximately 75 percent of haemoglobin is in the form of an alpha helix. The non helical stretches permit folding of the polypeptide upon itself. Individual residues can be assigned to one of eight helices (A-H) or to adjacent non helical stretches.

Heme iron is linked covalently to a histidine at the eighth residue of the F helix (His F8), at residue 87 of the alpha chain and residue 92 of the beta chain. Residues that have charged side groups, such as lysine, arginine, and glutamic acid, lie on the surface of the molecule in contact with the surrounding water solvent. Exposure of the hydrophilic (charged) amino acids to the aqueous milieu is an important determinant of the solubility of haemoglobin within the red blood cell and of the prevention of precipitation.

The haemoglobin tetramer is a globular molecule (5.0 x 5.4 x 6.4 nm) with a single axis of symmetry. The polypeptide chains are folded such that the four heme groups lie in clefts on the surface of the molecule equidistant from one another.

Overdosing on calcium-channel blockers should always be taken seriously and regarded as potentially fatal. Verapamil and diltiazem are the two most lethal calcium channel blockers in overdose. These work by binding the alpha-1 subunit of L-type calcium channels, preventing calcium from entering the cell. In cardiac myocytes, vascular smooth muscle cells, and islet beta-cells, these channels play an important role.

>10 tablets of verapamil (160 mg or 240 mg immediate or sustained-release capsules) or diltiazem can cause serious toxicity (180 mg, 240 mg or 360 mg immediate or sustained-release capsules)

In children, 1-2 tablets of verapamil or diltiazem (immediate or sustained-release)

Symptoms usually appear within 1-2 hours of ingestion with standard preparations. However, with slow-release preparations, significant toxicity may take 12-16 hours to manifest, with peak effects occurring after 24 hours.

The following are the main clinical features of calcium-channel blocker overdose:
Nausea and vomiting
Hypotension
Bradycardia and first-degree heart block
Myocardial ischaemia and stroke
Renal failure
Pulmonary oedema
Hyperglycaemia

The following are some of the most important bedside investigations to conduct:
Blood glucose
ECG
Arterial blood gas
Other investigations that can be helpful include
Urea & electrolytes
Chest X-ray (pulmonary oedema)
Echocardiography

The main factor in determining whether a substance is filtered or not is molecular weight. Molecules < 7 kDa in molecular weight e.g. glucose, amino acids, urea, ions are filtered freely, but larger molecules are increasingly restricted up to 70 kDa, and there is very little filtration for anything above this.
There is further restriction of negatively charged molecules because they are repelled by negative charges, particularly in the basement membrane. Albumin, which has a molecular weight of 69 kDa and is negatively charged, is filtered but only in very small amounts. All of the filtered albumin is reabsorbed in the proximal tubule. Small molecules such as ions, glucose, amino acids and urea pass the filter without hindrance. Other than the ultrafiltrate being essentially protein free, it has an otherwise identical composition of plasma. Bowman’s capsule consists of:
– an epithelial lining which consists of a single layer of cells called podocytes
– endothelium which is perforated by pores or fenestrations – this allows plasma components with a molecular weight of < 70 kDa to pass freely.