Compression of the thecal sac causes metastatic Spinal Cord Compression (MSCC) due to a Metastatic tumour and its components. It can cause symptoms of limb weakness, sensory disturbances and back pain depending on the extent and level of Compression. The most common source of a tumour causing MSCC is a prostate carcinoma that metastasized to the spinal cord via the vertebral venous plexus.

Gentamicin, an aminoglycoside antibiotic, acts by binding to the 30S subunit of the bacterial ribosome inhibiting the binding of aminoacyl-tRNA, and thus prevents initiation of protein synthesis.Two of its most notable side effects are reversible nephrotoxicity(caused by the inhibition of protein synthesis in renal cells, which causes acute tubular necrosis) and hearing loss (caused by damage to the vestibular apparatus of the inner ear). Both side effects are dose-related and occur commonly in the elderly.

Antidiuretic hormone (ADH), commonly known as vasopressin, is a peptide hormone that controls how much water the body retains.It is produced in the magnocellular and parvocellular neurosecretory cells of the paraventricular nucleus and supraoptic nucleus in the hypothalamus from a prohormone precursor. It is subsequently carried to the posterior pituitary via axons and stored in vesicles.The secretion of ADH from the posterior pituitary is regulated by numerous mechanisms:Increased plasma osmolality: Osmoreceptors in the hypothalamus detect an increase in osmolality and trigger ADH release.Stretch receptors in the atrial walls and big veins detect a decrease in atrial pressure as a result of this (cardiopulmonary baroreceptors). ADH release is generally inhibited by atrial receptor firing, but when the atrial receptors are stretched, the firing reduces and ADH release is promoted.Hypotension causes baroreceptor firing to diminish, resulting in increased sympathetic activity and ADH release.An increase in angiotensin II stimulates angiotensin II receptors in the hypothalamus, causing ADH production to increase.The main sites of action for ADH are:The kidney is made up of two parts. ADH’s main job is to keep the extracellular fluid volume under control. It increases permeability to water by acting on the renal collecting ducts via V2 Receptors (via a camp-dependent mechanism). This leads to a decrease in urine production, an increase in blood volume, and an increase in arterial pressure as a result.Vascular system: Vasoconstriction is a secondary function of ADH. ADH causes vasoconstriction via binding to V1 Receptors on vascular smooth muscle (via the IP3 signal transduction pathway). An increase in arterial pressure occurs as a result of this.

A furuncle, or boil, is a pyogenic infection of the hair follicle commonly caused by infection with Staphylococcus aureus. A carbuncle is a collection of individual boils clustered together. A bulla is a visible collection of clear fluid measuring greater than 0.5 cm in diameter. A vesicle is a visible collection of clear fluid measuring less than 0.5 cm in diameter.A pustule is a small visible skin elevation containing an accumulation of pus.

Acoustic neuroma is also called vestibular schwannoma (VS), acoustic neuroma, vestibular neuroma or acoustic neurofibroma. These are tumours that evolve from the Schwann cell sheath and can be either intracranial or extra-axial. They usually occur adjacent to the cochlear and vestibular nerves and most often arise from the inferior division of the latter. Anatomically, acoustic neuroma tends to occupy the cerebellopontine angle. About 5-10% of cerebellopontine angle (CPA) tumours are meningiomas and may occur elsewhere in the brain. Bilateral acoustic neuromas tend to be exclusively found in individuals with type 2 neurofibromatosis.The following nerves may be affected due to nerve compression:Facial nerve: usually minimal with late presentation except for very large tumours. Depending on the degree of engagement of the nerve, the symptoms may include twitching, increased lacrimation and facial weakness.Trigeminal Nerve: paraesthesia in the trigeminal distribution, tingling of the tongue, impairment of the corneal reflex, and less commonly pain which may mimic typical trigeminal neuralgia.Glossopharyngeal and Vagus nerves: palatal paresis, hoarseness of voice and dysphagia

Juxtacapillary receptors (J receptors) are sensory cells that are located within the alveolar walls in juxtaposition to the pulmonary capillaries of the lung.The J receptors are innervated by the vagus nerve and are activated by physical engorgement of the pulmonary capillaries or increased pulmonary interstitial volume, for example, in the presence of pulmonary oedema, pulmonary embolus, pneumonia and barotraumas. They may also be stimulated by hyperinflation of the lung.Stimulation of the J receptors causes a reflex increase in breathing rate and is also thought to be involved in the sensation of dyspnoea. The reflex response that is produced is apnoea, followed by rapid breathing, bradycardia, and hypotension.

Dexamethasone has a very high glucocorticoid activity in conjunction with insignificant mineralocorticoid activity. This makes it particularly suitable for high-dose therapy in conditions where fluid retention would be a disadvantage such as in the management of raised intracranial pressure or cerebral oedema secondary to malignancy. Dexamethasone also has a long duration of action and this, coupled with its lack of mineralocorticoid action makes it particularly suitable for suppression of corticotropin secretion in congenital adrenal hyperplasia. In most individuals a single dose of dexamethasone at night, is sufficient to inhibit corticotropin secretion for 24 hours. This is the basis of the ‘overnight dexamethasone suppression test’ for diagnosing Cushing’s syndrome.

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.

Like other non-steroidal anti-inflammatory drugs, Ibuprofen cannot be given with Warfarin as it would increase the bleeding risk of this patient.

Factors that increase glucagon secretion:↓ Blood glucose↑ Amino acidsCholecystokininCatecholaminesAcetylcholineFactors that decrease glucagon secretion:↑ Blood glucoseInsulinSomatostatinFatty acids, ketoacids

An overdose of levothyroxine can happen by accident or on purpose. Intentional overdosing is sometimes done to lose weight, but it can also happen in patients who are suicidal. The development of thyrotoxicosis, which can lead to excited sympathetic activity and high metabolism syndrome, is the main source of concern. The time between ingestion and the emergence of clinical features associated with an overdose is often quite long.After a levothyroxine overdose, the majority of patients are asymptomatic. Symptoms and signs are usually only seen in patients who have taken more than 10 mg of levothyroxine in total.The following are the most commonly seen clinical features in patients developing clinical features:TremorAgitationSweatingInsomniaHeadacheIncreased body temperatureIncreased blood pressureDiarrhoea and vomitingLess common clinical features associated with levothyroxine overdose include:SeizuresAcute psychosisThyroid stormTachycardiaArrhythmiasComaThe continued absorption of the ingested levothyroxine causes a progressive rise in both total serum T4 and total serum T3 levels in the first 24 hours after an overdose. However, in some cases, the biochemical picture is completely normal. Thyroid function tests are not always recommended after a thyroxine overdose. Although elevated thyroxine levels are common, they have little clinical significance and have no impact on treatment. Following a levothyroxine overdose, the following biochemical features are common:T4 and T3 levels in the blood are elevated.Free T4 and Free T3 levels are higher.TSH levels in the blood are low.If the patient is cooperative and more than 10 mg of levothyroxine has been consumed, activated charcoal can be given (i.e., likely to become symptomatic)Within an hour of ingestion, the patient presents.The treatment is mostly supportive and aimed at managing the sympathomimetic symptoms that come with levothyroxine overdose. If beta blockers aren’t an option, try propranolol 10-40 mg PO 6 hours or diltiazem 60-180 mg 8 hours.

Dietary fat is chiefly composed of triglycerides (esters of free fatty acids and glycerol which may be saturated or unsaturated). The essential fatty acids are linoleic acid and alpha-linoleic acid, which cannot be manufactured in the body. Dietary fat provides 37 kJ (9 kcal) of energy per gram. Fats are digested almost entirely in the small intestine and are only released from the stomach into the duodenum at the rate at which they can be digested.Pancreatic lipase is the most significant enzyme for fat digestion. In the duodenum fat is emulsified by bile acids, a process where larger lipid droplets are broken down into much smaller droplets providing a greater surface area for enzymatic digestion. Micelles are arranged so that hydrophobic lipid molecules lie in the centre, surrounded by bile acids arranged such the outer region is hydrophilic. Dietary and synthesised lipids are incorporated into chylomicrons in the Golgi body, which are exocytosed from the basolateral membrane to enter lacteals and thus the lymphatic system.

Features of intravascular haemolysis include:haemoglobinaemia, methaemalbuminaemia, haemoglobinuria (dark urine) and haemosiderinuria

Loperamide inhibits acetylcholine release from the myenteric plexus acts by action on opioid mu-receptors, and this then reduces bowel motility. The intestinal transit time is increased, thereby facilitating water reabsorption.

The DVLA sends a detailed information sheet about their licence and driving to all drivers with diabetes mellitus. The primary danger of driving while diabetic is hypoglycaemia.The DVLA must be notified of the following diabetic patients:All of the drivers are on insulin. (Licenses are being reviewed more frequently.)Those who are at high risk of hypoglycaemia and have had more than one episode of severe hypoglycaemia in the previous year. (Severe hypoglycaemia is defined as requiring the assistance of another person to manage.)Those who are unaware of their hypoglycaemiaAnyone who has ever been in a car accident due to hypoglycaemiaAnyone with diabetic retinopathy who needs laser treatment (to both eyes or to a second eye if sight only in one eye)Patients with diabetes complications that impair their ability to drive.To drive, drivers with insulin-treated diabetes must meet the following requirements:They need to be aware of hypoglycaemia.They must not have had more than one episode of hypoglycaemia in the previous 12 months that necessitated the assistance of another person.They must check their blood glucose levels no later than 2 hours before the first journey.While driving, they must check their blood glucose levels every two hours.The visual acuity and visual field standards must be met.Any significant changes in their condition must be reported to the DVLA. Furthermore, on days when they are not driving, group 2 licence holders must test their blood glucose twice daily using a metre that can store three months’ worth of readings.In addition to this advice, the DVLA also offers the following advice to diabetic patients:When taking tablets that have the potential to cause hypoglycaemia (such as sulfonylureas and glinides), monitoring may be necessary if there has been more than one episode of severe hypoglycaemia.Drivers must show good control and be able to recognise hypoglycaemia.Verify that your vision meets the required standard.If a patient feels hypoglycaemic or has a blood glucose level of less than 4.0 mmol/L, they should not drive. Driving should not be resumed until blood glucose levels have returned to normal, which should take 45 minutes.If there are any warning signs, patients should carry rapidly absorbed sugar in their vehicle and stop, turn off the ignition, and eat it.If resuscitation is required, a card stating which medications they are taking should be carried.If hypoglycaemia causes an accident, a diabetic driver may be charged with driving under the influence of drugs.

Depression of the eyeball is produced by the inferior rectus and the superior oblique muscles.

The anterior pituitary gland produces and secretes a peptide hormone called adrenocorticotropic hormone (ACTH) (adenohypophysis). It is secreted in response to the hypothalamus’s secretion of the hormone corticotropin-releasing hormone (CRH).ACTH promotes cortisol secretion via binding to cell surface ACTH receptors in the zona fasciculata of the adrenal cortex.ACTH also promotes the production of beta-endorphin, which is a precursor to melanocyte-releasing hormone (MRH).

Coagulative necrosis is the most common form of necrosis characterised by the loss of cell nuclei, but with general preservation of the underlying architecture. Dead tissue is macroscopically pale and firm. This is the classic pattern seen in myocardial infarction.Liquefactive necrosis leads to complete loss of cellular structure and conversion into a soft, semi-solid mass. This is typically seen in the brain following cerebral infarction.Caseous necrosis is most commonly seen in tuberculosis. Histologically, the complete loss of normal tissue architecture is replaced by amorphous, granular and eosinophilic tissue with a variable amount of fat and an appearance reminiscent of cottage cheese.Gangrenous necrosis is necrosis with putrefaction of tissues due to exposure to air (dry gangrene) or infection (wet gangrene).

A pareto diagram, or pareto chart, consists of a vertical bar graph in which values are plotted in decreasing order of relative frequency from left to right. The independent variables on the chart are shown on the horizontal axis and the dependent variables are portrayed as the heights of bars.A point-to-point graph, which shows the cumulative relative frequency, may be superimposed on the bar.Because the values of the statistical variables are placed in order of relative frequency, the graph clearly reveals which factors have the greatest impact and where attention is likely to yield the greatest benefit. It is extremely useful for analysing what problems need attention first, because the taller bars on the chart clearly illustrate which variable have the greatest cumulative effect on a given system.

Gastric emptying is decreased by the presence of fats in the duodenum (by stimulating release of cholecystokinin). Mixing of the food with gastric secretions takes place in the distal body and antrum of the stomach where the muscularis externa layer is thicker. The stomach has an additional inner oblique smooth muscle layer (in addition to the inner circular layer and outer longitudinal layer). Gastric emptying is increased by a low gastric pH and decreased by a low duodenal pH.

Pronator quadratus is a small, square-shaped muscle that lies in the anterior compartment of the forearm. It arises from the distal fourth of the anterior surface of the ulna and inserts into the distal fourth of the anterior surface of the radius.Pronator quadratus is innervated by the anterior interosseous nerve. It receives its blood supply from the anterior interosseous artery, which is a branch of the common interosseous artery, which in turn is a branch of the ulnar artery.The main action of pronator quadratus is to assist pronator teres with pronation of the forearm. The deep fibres bind the radius and ulna together.The pronator quadratus muscle highlighted in blue (adapted from Gray’s Anatomy)

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.

Caseous necrosis is most commonly seen in tuberculosis. Histologically, the complete loss of normal tissue architecture is replaced by amorphous, granular and eosinophilic tissue with a variable amount of fat and an appearance reminiscent of cottage cheese.

Macrolide antibiotics (e.g. clarithromycin and erythromycin) are cytochrome P450 enzyme inhibitors. They increase blood levels of theophylline leading to hypokalaemia, and potentially increasing the risk of Torsades de pointes when they are prescribed together. Co-prescription with theophylline should be avoided.Factors that enhance theophylline clearance include cigarette smoking, carbamazepine, phenobarbital, phenytoin, primidone, and rifampin. Medications that inhibit clearance include ethanol, ciprofloxacin, erythromycin, verapamil, propranolol, ticlopidine, tacrine, allopurinol, and cimetidine.

Treatment for oral candidiasis is with nystatin mouthwash. In unresponsive cases, oral fluconazole is used

The rate of baroreceptor firing slows down when blood pressure falls too low. This causes an increase in sympathetic stimulation of the heart, resulting in an increase in cardiac output. It also causes vasoconstriction by activating alpha 1 receptors in smooth muscle, which causes sympathetic stimulation of peripheral vessels. Alpha2 receptors can be found in both the brain and the peripheral nervous system. They control sympathetic outflow in the brain stem. Beta1 receptors, which are found on the cell membrane of cardiac muscle cells, stimulate heart rate and myocardial contractility. The smooth muscle cell membrane contains beta2 receptors, which promote smooth muscle relaxation in the lungs causing bronchodilation, GI tract, and peripheral blood vessels.

The current recommendation by NICE and the BNF is to use vancomycin as first-line in treatment of septicaemia related to vascular catheter. A broad-spectrum antipseudomonal beta-lactam antibiotic should be added to vancomycin if a Gram-negative sepsis is suspected especially in an immunocompromised patient.In any patient that has had a central venous catheter in situ for a period longer than a week, it should be suspected as the source of sepsis.The features suggesting the vascular catheter as the source of infection include:Presence of the catheter before onset of fever.The absence of another identifiable source of infection.Presence of inflammation or purulent material at the insertion site or along the tunnel.An immunocompetent patient without any underlying disease developing bacteraemia (or fungaemia).

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

Mycobacterium tuberculosis are part of the Mycobacteriaceae family. They are described to have the characteristics of a Gram-positive cell wall but they are not easily stained with Gram stain. This is because their cell wall contains a high lipid content, and this lipid allows the Mycobacteria to bind to alkaline stains with the application and help of heat. Once stained, they are able to resist decolorization even with the use of acid alcohol as the decolourizer, making them very difficult to decolorize, that is why they are known to be acid-fast.The Ghon complex is a non-pathognomonic radiographic finding on a chest x-ray that is significant for pulmonary infection of tuberculosis. The location of the Ghon’s focus is usually subpleural and predominantly in the upper part of the lower lobe and lower part of the middle or upper lobe. Skeletal tuberculosis of the spine is referred to as Pott disease.The risk of reactivation TB is about 3.3% during the first year after a positive PPD skin test and a total of 5% to 15% thereafter in the person’s lifetime. Progression from infection to active disease varies with age and the intensity and duration of exposure. Reactivation TB occurs when there is an alteration or suppression of the cellular immune system in the infected host that favoursreplication of the bacilli and progression to disease.

Angina pectoris is the most common symptom of ischemic heart disease and presents with chest pain relieved by rest and nitro-glycerine. Nitrates are the first-line treatment to relieve chest pain caused by angina. The commonly used nitrates are: 1. Glyceryl trinitrate 2. Isosorbide dinitrate The nitrate drugs are metabolized in the following steps: 1. Release Nitrite ions (NO2-), which are then converted to nitric oxide (NO) within cells. 2. NO activates guanylyl cyclase, which causes an increase in the intracellular concentration of cyclic guanosine-monophosphate (cGMP) in vascular smooth muscle cells. 3. Relaxation of vascular smooth muscle.Although nitrates are potent coronary vasodilators, their principal benefit in the management of angina results from a predominant mechanism of venous dilation:- Bigger veins hold more blood- Takes blood away from the left ventricle- Lowers LVEDV (preload), LA pressure- Less pulmonary oedema → improved dyspnoea