Leukotrienes increases (not decrease) vascular permeability during acute inflammation.

All the other statements are correct

Digoxin is most useful for controlling the ventricular response in persistent and permanent atrial fibrillation and atrial flutter. Digoxin is usually only effective for controlling the ventricular rate at rest, and should therefore only be used as monotherapy in predominantly sedentary patients with non-paroxysmal atrial fibrillation. It is now rarely used for rapid control of heart rate, as even with intravenous administration, response may take many hours. Digoxin is reserved for patients with worsening or severe heart failure due to left ventricular systolic dysfunction refractory to combination therapy with first-line agents. Digoxin is contraindicated in supraventricular arrhythmias associated with accessory conduction pathways e.g. Wolff-Parkinson-White syndrome.

The NICE guidelines for children and young people under 16 years lower UTIs are:
1. Get a urine sample before antibiotics are taken, and do a dipstick test OR send for culture and susceptibility
2. Assess and manage children under 5 with lower UTI with fever as recommended in the NICE guideline on fever in under 5s.
3. Prescribe an immediate antibiotic prescription and take into account the previous urine culture and susceptibility results, previous antibiotic use, which may have led to resistant bacteria
4. If urine culture and susceptibility report is sent
– Review the choice of antibiotic when the results are available AND
– change the antibiotic according to susceptibility results if the bacteria are resistant and symptoms are not improving, using a narrow-spectrum antibiotic wherever possible

The choice of antibiotics for non-pregnant young people under 16 years with lower UTI is summarised below:
1. Children under 3 months:
– Refer to paediatric specialist and treat with intravenous antibiotic in line with NICE guideline on fever in under 5s
2. Children over 3 months:
– First-choice
Nitrofurantoin – if eGFR >45 ml/minute
Trimethoprim – (if low risk of resistance*)
– Second-choice (no improvement in lower UTI symptoms on first-choice for at least 48 hours, or when first-choice not suitable)
Nitrofurantoin – if eGFR >45 ml/minute and not used as first-choice
Amoxicillin (only if culture results available and susceptible)
Cefalexin

Macrolide antibiotics are bacteriostatic.

They act by binding to the 50S subunit of the bacterial ribosome inhibit protein synthesis.

Macrolide antibiotics are actively concentrated within leukocytes, because of this, they are transported into the site of infection.

Macrolide antibiotics are not effective in meningitis as they do not penetrate the central nervous system well.

They are mainly against Gram-positive organisms and can be used as an alternative in patients with penicillin allergy.

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 favours
replication of the bacilli and progression to disease.

Clinical features of hypoglycaemia:
Autonomic  symptoms: Sweating, feeling hot, anxiety/agitation, palpitations, shaking, paraesthesia, dizziness
Neuroglycopaenic symptoms: Weakness, blurred vision, difficulty speaking, poor concentration, poor coordination, drowsiness, confusion, seizures, coma
Other symptoms: Nausea, fatigue, hunger

A commensal is an organism that is part of the normal flora.

Acute mild to moderate disease affecting the rectum (proctitis) or the rectosigmoid is treated initially with local application of an aminosalicylate; alternatively, a local corticosteroid can be used but it is less effective. A combination of a local aminosalicylate and a local corticosteroid can be used for proctitis that does not respond to a local aminosalicylate alone.

Because digoxin has a narrow therapeutic index, it can cause toxicity both during long-term therapy and after an overdose. Even when the serum digoxin concentration is within the therapeutic range, it can happen.

Acute digoxin toxicity usually manifests itself within 2-4 hours of an overdose, with serum levels peaking around 6 hours after ingestion and life-threatening cardiovascular complications following 8-12 hours.

Chronic digoxin toxicity is most common in the elderly or those with impaired renal function, and it is often caused by a coexisting illness. The clinical signs and symptoms usually appear gradually over days to weeks.

The following are characteristics of digoxin toxicity:
Nausea and vomiting
Diarrhoea
Abdominal pain
Confusion
Tachyarrhythmias or bradyarrhythmias
Xanthopsia (yellow-green vision)
Hyperkalaemia (early sign of significant toxicity)

Some precipitating factors are as follows:
Elderly patients
Renal failure
Myocardial ischaemia
Hypokalaemia
Hypomagnesaemia
Hypercalcaemia
Hypernatraemia
Acidosis
Hypothyroidism
Spironolactone
Amiodarone
Quinidine
Verapamil
Diltiazem

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%)

Darcy’s law states that flow through a tube is dependent on the pressure differences across the ends of the tube (P1 – P2) and the resistance to flow provided by the tube (R). Resistance is due to frictional forces and is determined by the length of the tube (L), the radius of the tube (r) and the viscosity of the fluid flowing down that tube (V). The radius of the tube has the largest effect on resistance and therefore flow – this explains why smaller gauge cannulas with larger diameters have a faster rate of flow. Increased viscosity, as seen in polycythemia, will slow the rate of blood flow through a vessel.

The auriculotemporal nerve is irritated by mumps, which results in significant discomfort due to inflammation and swelling of the parotid gland, as well as the stretching of its capsule. Compression caused by swallowing or chewing exacerbates pain.

Tendinopathy and spontaneous tendon rupture are caused by fluoroquinolones, which are an uncommon but well-known cause. Tendon problems caused by fluoroquinolones are expected to affect 15 to 20 people per 100,000. Patients over the age of 60 are most likely to develop them.

It usually affects the Achilles tendon, but it has also been described in cases involving the quadriceps, peroneus brevis, extensor pollicis longus, long head of biceps brachii, and rotator cuff tendons. The exact aetiology is uncertain, although the fluoroquinolone medication is thought to obstruct collagen activity and/or cut off blood supply to the tendon.

Other factors linked to tendon rupture spontaneously include:
Gout
Treatment with corticosteroids
Hypercholesterolaemia
Long-term dialysis
Kidney transplant
Rheumatoid arthritis 

One of the complications that polycystic kidney disease may cause is the development of a brain aneurysm.

A berry aneurysm is the most common type of brain aneurysm.

The Circle of Willis, where the major blood vessels meet at the base of the brain, is where it usually appears. The most common junctions of the Circle of Willis where an aneurysm may occur include the anterior communicating artery (35%), internal carotid artery (30%), the posterior communicating artery and the middle cerebral artery (22%), and finally, the posterior circulation sites, most commonly the basilar artery tip.

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.

The cervical spinal cord is the section of the spinal cord that goes through the bones of the neck.

It is injured incompletely in the central cord syndrome (CCS). This will result in arm weakness more than leg weakness.

Escherichia coli O157 is a serotype of Escherichia coli.
The Escherichia coliO157 strain is ‘enterohaemorrhagic’ and causes severe forms of acute haemorrhagic diarrhoea. It can also cause non-haemorrhagic diarrhoea.

Incubation period of Escherichia coli O157 is usually 3-4 days and bloody diarrhoea usually begins on the 3rd or 4th day of the infection.

Infections with Escherichia coliO157 are more common during the warmer months than in winter.

Haemolytic uraemic syndrome develops in approximately 6% of patients. It is commonly seen in children and in the elderly.

Escherichia coli O157 can also cause:
Haemorrhagic colitis
Haemolytic uraemic syndrome
Thrombotic thrombocytopenic purpura but not immune thrombocytopenic purpura.

Haemoglobin is composed of four polypeptide globin chains each with its own iron containing haem molecule. Haem synthesis occurs largely in the mitochondria by a series of biochemical reactions commencing with the condensation of glycine and succinyl coenzyme A under the action of the key rate-limiting enzyme delta-aminolevulinic acid (ALA) synthase. The globin chains are synthesised by ribosomes in the cytosol. Haemoglobin synthesis only occurs in immature red blood cells.
There are three types of haemoglobin in normal adult blood: haemoglobin A, A2 and F:
– Normal adult haemoglobin (HbA) makes up about 96 – 98 % of total adult haemoglobin, and consists of two alpha (α) and two beta (β) globin chains. 
– Haemoglobin A2 (HbA2), a normal variant of adult haemoglobin, makes up about 1.5 – 3.5 % of total adult haemoglobin and consists of two α and two delta (δ) globin chains.
– Foetal haemoglobin is the main Hb in the later two-thirds of foetal life and in the newborn until approximately 12 weeks of age. Foetal haemoglobin has a higher affinity for oxygen than adult haemoglobin. 
Red cells are destroyed by macrophages in the liver and spleen after , 120 days. The haem group is split from the haemoglobin and converted to biliverdin and then bilirubin. The iron is conserved and recycled to plasma via transferrin or stored in macrophages as ferritin and haemosiderin. An increased rate of haemoglobin breakdown results in excess bilirubin and jaundice.

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.

Negative predictive value (NPV) is the proportion of individuals with a negative test result who do not have the disease.
Negative predictive value (NPV) = d/(c+d)
= 798/800
= 0.99 = 99%
This means there is a 99% chance, if the test is negative, that the patient does not have a DVT.

The correct administration of IV adrenaline 1 mg (10 mL of 1:10,000 solution) is that it should be given after 3 shocks and every 3 – 5 minutes/after alternate shocks thereafter.

In most cases of atrial flutter, ventricular rate control is used as a stopgap measure until sinus rhythm is restored. A beta-blocker (e.g. bisoprolol), diltiazem, or verapamil can be used to reduce the rate of contractions in the heart.
Electrical cardioversion, pharmacological cardioversion, and catheter ablation can all be used to return the heart to a normal rhythm. Cardioversion should not be attempted until the patient has been fully anticoagulated for at least three weeks if the duration of atrial flutter is unknown or it has lasted longer than 48 hours. Emergency electrical cardioversion is the treatment of choice when there is a sudden onset of symptoms and haemodynamic compromise. For recurrent atrial flutter, catheter ablation is preferred.

Verapamil is a calcium-channel blocker that is non-dihydropyridine phenylalkylamine and can be used to treat supraventricular arrhythmias. It’s a calcium channel blocker with a high negative inotropic effect that lowers cardiac output, slows the heart rate, and may impair atrioventricular conduction. At high doses, it can cause heart failure, exacerbate conduction disorders, and cause hypotension.

Adults should take 240-480 mg of verapamil in 2-3 divided doses. 5-10 mg IV over 30 seconds is the corresponding intravenous (IV) dose. After an IV injection, the peak effect lasts 3-5 minutes, and the action lasts 10-20 minutes.

Verapamil should not be taken with beta-blockers like atenolol or quinidine because the combination of their negatively inotropic and negatively chronotropic effects can result in severe hypotension, bradycardia, impaired atrioventricular conduction, heart failure (due to impaired cardiac contractility), and sinus arrest.
The use of verapamil is contraindicated in the following situations:
Acute porphyrias are a type of porphyria that occurs suddenly.
Accessory conducting pathways are linked to atrial flutter or fibrillation (e.g. Wolff-Parkinson-White-syndrome)
Bradycardia
Shock caused by the heart
Insufficiency of the heart (with reduced ejection fraction)
Left ventricular function has been significantly harmed in the past (even if controlled by therapy)
Hypotension (blood pressure less than 90 mmHg)
AV block in the second and third degrees
Sinusitis is a condition in which the sinuses become
Sino-atrial occlusion

A CT pulmonary angiogram is an angiogram of the blood vessels of the lungs. It is a diagnostic imaging test used to check for pulmonary embolism.

A pulmonary embolism is caused by a blood clot or thrombus that has become lodged in an artery in the lung and blocks blood flow to the lung. A patient with pulmonary embolism may feel an abrupt onset of pleuritic chest pain, shortness of breath, and hypoxia. Also, pulmonary embolism can result in alveolar dead space.

Dead space represents the volume of ventilated air that does not participate in gas exchange. The alveolar dead space is caused by ventilation/perfusion imbalances in the alveoli. It is defined as the sum of the volumes of alveoli that are ventilated but not perfused.

Aside from pulmonary embolism, smoking, bronchitis, emphysema, and asthma are among the other causes of alveolar dead space.

The other types of dead space are the following: Anatomical dead space is the portion of the airways that conducts gas to the alveoli. This is usually around 150 mL, and there is no possibility of gas exchange in these areas. Physiological dead space is the sum of anatomical and alveolar dead spaces.

Physiological dead space can account for up to 30% of the tidal volume.

Hyponatraemia refers to a serum sodium concentration < 135 mmol/L.
It is safer to quickly correct acute hyponatremia than chronic hyponatremia but correction should not be too fast, especially in chronic hyponatraemia, because of the risk of central pontine myelinolysis. Hyponatraemia is usually associated with a low plasma osmolality.
Under normal circumstances, if serum osmolality is low, then urine osmolality should also be low because the kidneys should be trying to retain solute.
In SIADH, excess ADH causes water retention, but not the retention of solute. Therefore, urine that is concentrated and relatively high in sodium is produced, even though the serum sodium is low (urine osmolality > 100 mosmol/kg).

Hand-foot syndrome in children is typically the first symptom of the disease, produced by infarction of the metaphysis of small bones. The disease is inherited as an autosomal recessive trait. By adulthood, the spleen has usually infarcted. Infection with the B19 parvovirus is usually followed by an aplastic crisis. Thrombocytopenia is caused by splenic sequestration.

Flexor carpi radialis is innervated by the median nerve.

Codeine phosphate is a weak opioid and can be used for the relief of mild to moderate pain where other painkillers such as paracetamol or ibuprofen have proved ineffective.Codeine is metabolised to morphine which is responsible for its therapeutic effects. Codeine 240 mg is approximately equivalent to 30 mg of morphine. The capacity to metabolise codeine can vary considerably between individuals; there is a marked increase in morphine toxicity in people who are ultra rapid metabolisers, and reduced therapeutic effect in poor codeine metabolisers. Codeine is contraindicated in patients of any age who are known to be ultra-rapid metabolisers of codeine (CYP2D6 ultra-rapid metabolisers).Codeine is also contraindicated in children under 12, and in children of any age who undergo the removal of tonsils or adenoids for the treatment of obstructive sleep apnoea due to reports of morphine toxicity.

Aspirin irreversibly inhibits cyclooxygenase and blocks the platelet production of thromboxane A2 (TXA2), thus inhibiting platelet aggregation.

Lactic acidosis is defined as a pH <7.35 and a lactate >5 mmol/L. It is a common finding in critically ill patients and is often associated with other serious underlying pathologies. The anion gap is raised in lactic acidosis.
There are major adverse consequences of severe acidaemia, which affect all body systems, and there is an associated increase in mortality of critically ill patients with a raised lactate. The mortality associated with lactic acidosis despite full supportive treatment remains at 60-90%.
Acquired lactic acidosis is classified into two subtypes:
Type A is due to tissue hypoxia
Type B is due to non-hypoxic processes affecting the production and elimination of lactate
Lactic acidosis can be extreme after a seizure but usually resolves spontaneously within a few hours.
Left ventricular failure typically results in tissue hypoperfusion and a type A lactic acidosis.
Some causes of type A and type B lactic acidosis are shown below:
Type A lactic acidosis
Type B lactic acidosis
Shock (including septic shock)
Left ventricular failure
Severe anaemia
Asphyxia
Cardiac arrest
CO poisoning
Respiratory failure
Severe asthma and COPD
Regional hypoperfusion
Renal failure
Liver failure
Sepsis (non-hypoxic sepsis)
Thiamine deficiency
Alcoholic ketoacidosis
Diabetic ketoacidosis
Cyanide poisoning
Methanol poisoning
Biguanide poisoning

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 valves
Congenital heart defects
Prior history of endocarditis
Rheumatic fever
Illicit intravenous drug use

In the presentation of endocarditis, the following triad is often quoted:
Persistent fever
Embolic phenomena
New or changing murmur

A combination of vancomycin, rifampicin and gentamicin is advised if the patient has a cardiac prostheses, is penicillin allergic, or if methicillin-resistant Staphylococcus aureus (MRSA) is suspected. In this case the patient has a prosthetic valve making this the most appropriate initial treatment regimen.

Flucloxacillin and gentamicin are current recommended by NICE and the BNF for the initial ‘blind’ therapy in endocarditis. This patient has prostheses and this is not the most appropriate initial treatment regimen.

Other features that may be present include heart failure, splenomegaly, finger clubbing, renal features (haematuria, proteinuria, nephritis), and vasculitic features (splinter haemorrhages, Osler’s nodes, Janeway lesions, Roth’s spots).