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.

Glucagon is a peptide hormone that is produced and secreted by alpha cells of the islets of Langerhans, which are located in the endocrine portion of the pancreas. The main physiological role of glucagon is to stimulate hepatic glucose output, thereby leading to increases in glycaemia. It provides the major counter-regulatory mechanism to insulin in maintaining glucose homeostasis.Hypoglycaemia is the principal stimulus for the secretion of glucagon but may also be used as an antidote in beta-blocker overdose and in anaphylaxis in patients on beta-blockers that fail to respond to adrenaline. Glucagon then causes:GlycogenolysisGluconeogenesisLipolysis in adipose tissueThe secretion of glucagon is also stimulated by:AdrenalineCholecystokininArginineAlanineAcetylcholineThe secretion of glucagon is inhibited by:InsulinSomatostatinIncreased free fatty acidsIncreased urea productionGlycolysis is the metabolic pathway that converts glucose into pyruvate. The free energy released by this process is used to form ATP and NADH. Glycolysis is inhibited by glucagon, and glycolysis and gluconeogenesis are reciprocally regulated so that when one cell pathway is activated, the other is inactive and vice versa.Glucagon has a minor effect of enhancing lipolysis in adipose tissue. Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into glycerol and free fatty acids. It makes fatty acids available for oxidation.

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.

25-year-old receives immunoglobulin and vaccination after cutting her hand on a drinking glass and not knowing her vaccination history.Because this is not a tetanus-prone wound, immunoglobulin is not recommended. Because you can’t be sure about her vaccination history, now is the best time to start a tetanus vaccination course to ensure coverage later in life. The first vaccination should be administered at the time of presentation; the patient’s own GP should then review the patient’s vaccination history and schedule the rest of the course as needed.8-year-old whose hand was cut with a kitchen knife, received her first round of vaccinations as a baby and a booster at the age of four – receives vaccination:The tetanus vaccinations for this child are up to date, and the next booster should not be given too soon. Immunoglobulin is not required because this is not a tetanus-prone wound.80-year-old diabetic, a rusty nail went through his shoe and into his foot while walking in the woods, and he was uncertain of his vaccination history – he received vaccination and immunoglobulin:A tetanus vaccination course may not have been completed by an 80-year-old UK resident (the vaccination was introduced in 1961). The vaccination should be given at a walk-in clinic, and the patient’s own GP should be contacted to confirm vaccination history and to schedule the rest of the course as needed. Because this is a tetanus-prone wound (puncture wound and potential soil contact), immunoglobulin would be recommended in a patient with incomplete tetanus vaccinations.A 28-year-old Polish man cuts his leg while working in the garden, the wound is heavily contaminated with soil, and his vaccination history is unknown – he receives vaccination:In a patient with an unknown vaccination history, this is a tetanus-prone wound. In this case, the best course of action would be to administer both the vaccination and immunoglobulin at the walk-in clinic, then contact the patient’s own GP to check his or her vaccination history and schedule the rest of the course as needed.30-year-old with a large amount of devitalized tissue in the torso from an electrical burn – has had all vaccinations, so no need for vaccination or immunoglobulin:Because this is a high-risk tetanus wound (with a lot of devitalized tissue), even if the patient has had a full course of vaccinations in the past, immunoglobulin is recommended. There is no need for any additional vaccinations.

Gastrin secretion is inhibited by:Low gastric pH (negative feedback mechanism)SomatostatinSecretinGastric inhibitory polypeptide (GIP)Cholecystokinin

End-organ damage (e.g. encephalopathy, intracranial haemorrhage, acute myocardial infarction or ischaemia, dissection, pulmonary oedema, nephropathy, eclampsia, papilledema, and/or angiopathic haemolytic anaemia) characterises a hypertensive emergency (also known as ‘accelerated hypertension’ or malignant hypertension’ It’s a life-threatening condition that necessitates rapid blood pressure reduction to avoid end-organ damage and a negative outcome.Hypertensive encephalopathy is a syndrome that includes headaches, seizures, visual changes, and other neurologic symptoms in people who have high blood pressure. It is reversible if treated quickly, but it can progress to coma and death if not treated properly.Any patient with suspected hypertensive encephalopathy should have an urgent CT scan to rule out an intracranial haemorrhage, as rapid blood pressure reduction could be dangerous in these circumstances.The drug of choice is labetalol, which reduces blood pressure steadily and consistently without compromising cerebral blood flow.An initial reduction of approximately 25% in mean arterial pressure (MAP) over an hour should be aimed for, followed by a further controlled MAP reduction over the next 24 hours. In patients who are unable to take beta-blockers, nicardipine can be used as a substitute.

Mannitol is the most widely used osmotic diuretic that is most commonly used to reduce cerebral oedema and intracranial pressure. It is recommended to use mannitol for the reduction of CSF pressure/cerebral oedema in a dose of 0.25-2 g/kg as an intravenous infusion over 30-60 minutes. This can be repeated 1-2 times after 4-8 hours if needed.Mannitol has several contraindications and some of them are listed below:1. Anuria due to renal disease2. Acute intracranial bleeding (except during craniotomy)3. Severe cardiac failure4. Severe dehydration5. Severe pulmonary oedema or congestion6. Known hypersensitivity to mannitol

End-organ damage (e.g. encephalopathy, intracranial haemorrhage, acute myocardial infarction or ischaemia, dissection, pulmonary oedema, nephropathy, eclampsia, papilledema, and/or angiopathic haemolytic anaemia) characterises a hypertensive emergency (also known as ‘accelerated hypertension’ or malignant hypertension’ It’s a life-threatening condition that necessitates rapid blood pressure reduction to avoid end-organ damage and a negative outcome.Hypertensive encephalopathy is a syndrome that includes headaches, seizures, visual changes, and other neurologic symptoms in people who have high blood pressure. It is reversible if treated quickly, but it can progress to coma and death if not treated properly.Any patient with suspected hypertensive encephalopathy should have an urgent CT scan to rule out an intracranial haemorrhage, as rapid blood pressure reduction could be dangerous in these circumstances.The drug of choice is labetalol, which reduces blood pressure steadily and consistently without compromising cerebral blood flow.An initial reduction of approximately 25% in mean arterial pressure (MAP) over an hour should be aimed for, followed by a further controlled MAP reduction over the next 24 hours. In patients who are unable to take beta-blockers, nicardipine can be used as a substitute.

Cryptococcus neoformans typically causes infection in patients with lymphoma, those taking steroid or cytotoxic therapy, those with T-cell deficiency e.g. AIDS and those with intense exposure, such as pigeon fanciers.

Thoracotomy describes an incision made in the chest wall to access the contents of the thoracic cavity. Thoracotomies typically can be divided into two categories; anterolateral thoracotomies and posterolateral thoracotomies. These can be further subdivided into supra-mammary and infra-mammary and, of course, further divided into the right or left chest. Each type of incision has its utility given certain circumstances.A scalpel is used to sharply divide the skin along the inframammary crease overlying the fifth rib. Electrocautery is then used to divide the pectoralis major muscle and serratus anterior muscle. Visualization of the proper operative field can be achieved with the division and retraction of the latissimus dorsi. Either the fourth or fifth intercostal space is then entered after the division of intercostal muscles above the rib to ensure the preservation of the neurovascular bundle. Once the patient is properly secured to the operating table, the ipsilateral arm is raised and positioned anteriorly and cephalad to rest above the head. The incision is started along the inframammary crease and extended posterolaterally below the tip of the scapula. It is then extended superiorly between the spine and the edge of the scapula, a short distance. The trapezius muscle and the subcutaneous tissues are divided with electrocautery. The serratus anterior and latissimus dorsi muscles are identified and can be retracted. The intercostal muscles are then divided along the superior border of the ribs, and the thoracic cavity is accessed.

Heart Sound – Phase of Cardiac Cycle – Mechanical Event:First heart sound – Start of systole – Caused by closure of the atrioventricular (mitral & tricuspid) valvesSecond heart sound – End of systole – Caused by closure of the semilunar (aortic and pulmonary) valvesThird heart sound – Early diastole – Caused by rapid flow of blood from the atria into the ventricles during the ventricular filling phaseFourth heart sound – Late diastole – Caused by filling of an abnormally stiff ventricle in atrial systole

Entonox is a mixture of 50% Oxygen and 50% nitrous oxide and is given in an inhaled form as a quick form of analgesia. Entonox causes non-competitive inhibition of NMDA (N-methyl-D-aspartate) receptors, which are a subtype of the glutamate receptor. It is stored in blue and white cylinders and administered via a pressure regulator and demand valve. The administration of this medicine reduces pain and anxiety in paediatric and dental procedures ands during labour. Effects are apparent after 20 seconds, and peak action occurs after 3 to 5 minutes as it is a drug with a rapid onset and the patient will also recover rapidly from its effects. Entonox is widely used as it does not accumulate in the body and does not cause many side effects. However, a notable side effect is the inhibition of Vitamin B12 synthesis.

The following are the lesions of the cranial nerves:1. Olfactory nerve (I)Reduced taste and smell, but not to ammonia which stimulates the pain fibres carried in the trigeminal nerve2. Optic nerve (II)Manifested by visual field defects, pupillary abnormalities, optic neuritis, optic atrophy, papilledema3. Oculomotor nerve (III)A fixed, dilated pupil which doesn’t accommodate, ptosis, complete internal ophthalmoplegia (masked by ptosis), unopposed lateral rectus causes outward deviation of the eye. If the ocular sympathetic fibres are also affected behind the orbit, the pupil will be fixed but not dilated.4. Trochlear nerve (IV)Diplopia due to weakness of downward and inward eye movement. The most common cause of a pure vertical diplopia. The patient tends to compensate by tilting the head away from the affected side.5. Trigeminal nerve (V)Reduced sensation or dysesthesia over the affected area. Weakness of jaw clenching and side-to-side movement. If there is a lower motor neuron (LMN) lesion, the jaw deviates to the weak side when the mouth is opened. There may be fasciculation of temporalis and masseter.6. Abducens nerve (VI)Inability to look laterally. The eye is deviated medially because of unopposed action of the medial rectus muscle.7. Facial nerve (VII)Facial weakness. In an LMN lesion the forehead is paralysed – the final common pathway to the muscles is destroyed; whereas the upper facial muscles are partially spared in an upper motor neurone (UMN) lesion because of alternative pathways in the brainstem. There appear to be different pathways for voluntary and emotional movement. CVAs usually weaken voluntary movement, often sparing involuntary movements (e.g., spontaneous smiling). The much rarer selective loss of emotional movement is called mimic paralysis and is usually due to a frontal or thalamic lesion.8. Vestibulocochlear nerve (VIII)Unilateral sensorineural deafness, tinnitus. Slow-growing lesions seldom present with vestibular symptoms as compensation has time to occur.9. Glossopharyngeal nerve (IX)Unilateral lesions do not cause any deficit because of bilateral corticobulbar connections. Bilateral lesions result in pseudobulbar palsy. These nerves are closely interlinked.10. Vagus nerve (X)Palatal weakness can cause ‘nasal speech’ and nasal regurgitation of food. The palate moves asymmetrically when the patient says ‘ahh’. Recurrent nerve palsy results in hoarseness, loss of volume and ‘bovine cough’.11. Accessory nerve (XI)Weakness and wasting of sternocleidomastoid and trapezius muscles12.Hypoglossal nerve (XII)An LMN lesion produces wasting of the ipsilateral side of the tongue, with fasciculation; and on attempted protrusion the tongue deviates towards the affected side, but the tongue deviates away from the side of a central lesion.

Endocarditis is infective or non infective inflammation (marantic endocarditis) of the inner layer of the heart and it often involves the heart valves.Risk factors include:Prosthetic heart valvesCongenital heart defectsPrior history of endocarditisRheumatic feverIllicit intravenous drug useIn the presentation of endocarditis, the following triad is often quoted:Persistent feverEmbolic phenomenaNew or changing murmurFlucloxacillin and gentamicin are current recommended by NICE and the BNF for the initial ‘blind’ therapy in endocarditis.

Digoxin is excreted through the kidneys, and impaired renal function can lead to elevated digoxin levels and toxicity.The patient’s digoxin dose should be reduced in this case, and their digoxin level and electrolytes should be closely monitored.

Normal saline (sodium chloride 0.9%) contains:Na+150 mmol/LCl-150 mmol/L

Nail clippings for microscopy and culture are a diagnostic test for fungal infection. Because some fungi are restricted to the lower parts of the nail, clippings should be taken from the discoloured or brittle parts and cut back as far as possible from the free edge.

Paroxysmal nocturnal haemoglobinuria is an acquired genetic disorder that causes a decrease in red blood cells due to a membrane defect that allows increased complement binding to RBCs, causing haemolysis. Patients complain of dark-coloured urine first in the morning due to haemoglobinuria secondary to lysis of red blood cells overnight. Thrombosis occurs, which affects hepatic, abdominal, cerebral and subdermal veins. Thrombosis of hepatic veins can lead to Budd-Chiari syndrome, thrombosis of subdermal veins can lead to painful nodules on the skin, and thrombosis of cerebral vessels can lead to stroke. The presence of dark urine in the morning only and at no other time differentiates this condition from other conditions.Multiple myeloma would present with bone pain, signs of radiculopathy if there were nerve root compression and a history of repeated infections. Patients with Non-Hodgkin Lymphoma would complain of enlarged lymph nodes, fatigue, fever, weight loss and a history of repeated infections. Acute lymphoblastic leukaemia presents more commonly in children than in adults. The patient would complain of bone pain, and on examination, there would be hepatosplenomegaly.

ACTH secretion is stimulated by corticotropin-releasing hormone (CRH) from the hypothalamus.

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.

Adverse effects include:Antimuscarinic effects: Dry mouth, Blurred vision, Constipation, Urinary retention, Sedation, ConfusionCardiovascular effects: Heart block, Arrhythmias, Tachycardia, Postural hypotension, QT-interval prolongation, Hepatic impairment, Narrow-angle glaucoma

A vesicle is a visible collection of fluid measuring less than 0.5 cm in diameter.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 pustule is a small visible skin elevation containing an accumulation of pus.

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.

Angiotensin I is converted to angiotensin II by the removal of two C-terminal residues by the enzyme angiotensin-converting enzyme (ACE). This primarily occurs in the lungs, although it does also occur to a lesser degree in endothelial cells and renal epithelial cells.The main actions of angiotensin II are:Vasoconstriction of vascular smooth muscle (resulting in increased blood pressure)Vasoconstriction of the efferent arteriole of the glomerulus (resulting in an increased filtration fraction and preserved glomerular filtration rate)Stimulation of aldosterone release from the zona glomerulosa of the adrenal cortexStimulation of anti-diuretic hormone (vasopressin) release from the posterior pituitaryStimulation of thirst via the hypothalamusActs on the Na+/H+ exchanger in the proximal tubule of the kidney to stimulate Na+reabsorption and H+excretion

Cellular respiration is the process by which cells obtain energy in the form of adenosine triphosphate (ATP). ATP transfers chemical energy from the energy rich substances in the cell to the cell’s energy requiring reactions e.g. active transport, DNA replication and muscle contraction.Cellular respiration is essentially a three step process: 1) Glycolysis, 2)The Krebs cycle, 3)The electron transfer system.The main respiratory substrate used by cells is 6-carbon glucose. Fats and proteins can also be used as respiratory substrates. When fats are being used as the primary energy source, in the absence of glucose, an excess amount of acetyl-CoA is produced, and is converted into acetone and ketone bodies. This can occur in starvation, fasting or in diabetic ketoacidosis. Proteins are used as an energy source only if protein intake is very high, or if glucose and fat sources are depleted.

Alteplase is a recombinant tissue-type plasminogen activator (tPA), a naturally occurring fibrin-specific enzyme that has selectivity for activation of fibrin-bound plasminogen. It has a short half-life of 3 – 4  minutes and must be given by continuous intravenous infusion but is not associated with antigenic or hypotensive effects, and can be used in patients when recent streptococcal infections or recent use of streptokinase contraindicates the use of streptokinase.

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 daysCough (usually non-productive and occurs in approximately 90%)Pleuritic chest painHaemoptysisHeadacheNausea, vomiting and diarrhoeaAnorexiaLegionella 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.

IV Lidocaine is indicated in Ventricular Arrhythmias or Pulseless Ventricular Tachycardia (after defibrillation, attempted CPR, and vasopressor administration)

Absolute risk and relative risk are used to assess the strength of a relationship between a disease and a factor that may affect it.Absolute risk (AR) is the risk of developing a disease over a time period:AR = the number of events that occur in a group / number of people in that groupThe absolute risk reduction (ARR) is the difference between the absolute risk in the control group (ARC) and the absolute risk in the treated group (ART). ARR = ARC – ARTThe control group is the warfarin group, therefore the ARC is 20/500 (0.04). Treatment group is the ticagrelor group and ART = 30/300 (0.1). ARR = 0.04 – 0.1 = -0.06. This shows that treatment with ticagrelor increases risk of developing stroke. This is also termed a relative risk increase.Relative risk, or risk ratio, (RR) is used to compare the risk in the two different groups. It is the ratio of the absolute risks of the disease in the treatment group (ART) to the absolute risk of the disease in the control group (ARC):RR=ART /ARCTherefore RR = 0.1 / 0.04 = 2.5RR < 1 means the intervention reduces the risk of the outcome being studiedRR = 1 means the treatment has no effect on the outcome being studiedRR > 1 means the intervention increased the risk of the outcome being studiedSince RR is 2.5, ticagrelor increases the risk of stroke.SUMMARYAbsolute risk reduction is -0.06Absolute risk in warfarin group = 0.04Relative risk = 2.5Ticagrelor has no effect on stroke is incorrect because RR is not =1

Relative risk (RR) is a ratio of the probability of an event occurring in the exposed group versus the probability of the event occurring in the non-exposed group.RR can be computed as the absolute risk of events in the treatment group (ART), divided by the absolute risk of events in the control group (ARC).RR = ART/ARCRR = (30/300) / (20/500)RR = 2.5Recall that:If RR < 1, then the intervention reduces the risk of the outcome.If RR = 1, then the treatment has no effect on the outcome.If RR > 1, then the intervention increases the risk of the outcome.