Bumetanide is 40 times more powerful than furosemide, and one milligram is roughly equivalent to 40 milligrams of furosemide. This patient is currently taking 80 mg of furosemide and should be switched to a 2 mg bumetanide once daily.

The hydrostatic pressure along the length of the capillary is usually greater than plasma oncotic pressure. As a result, there is a small net filtration of fluid from the capillary into the interstitial space. The regulation of blood flow into the microcirculation is via the vasoconstriction of small arterioles, which is activated by the sympathetic nervous system through numerous nerve endings in their walls. Unlike proteins, most ions and small molecules diffuse easily across capillary walls and thus the crystalloid osmotic pressure they exert is roughly the same on either side of the capillary wall. Because the plasma colloid osmotic pressure is higher than interstitial colloid osmotic, fluid is drawn intravascularly. A reduction of hydrostatic capillary pressure and transient increase in absorption of fluid is a result of arteriolar constriction.

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 cortex
Stimulation of anti-diuretic hormone (vasopressin) release from the posterior pituitary
Stimulation of thirst via the hypothalamus
Acts on the Na+/H+ exchanger in the proximal tubule of the kidney to stimulate Na+reabsorption and H+excretion

Rodents and domestic animals are the primary reservoirs for the Leptospira spp, although other animals, including cows, horses, mongooses, and frogs, can also harbour the leptospires. Humans may be directly infected from animal urine or indirectly by contact with soil or water that is contaminated with urine from infected animals. Infected humans can shed leptospires in urine for up to 11 months, infected cows for 3.5 months, infected dogs for 4 years, and infected rodents possibly for their entire lifetime.

The organisms enter the host through mucous membranes or abraded skin. The incubation period ranges from 5 to 14 days.

Amiodarone is an anti-arrhythmic medication that can be used to treat both ventricular and atrial arrhythmias. It’s a class III anti-arrhythmic that works by blocking a variety of channels, including Na+ and K+ channels, as well as beta-adrenoreceptors. As a result, it slows conduction through the SA and AV nodes and prolongs phase 3 of the cardiac action potential (slowing repolarisation).

First-line treatment is with intravenous lorazepam if available. Intravenous diazepam is effective but it carries a high risk of thrombophlebitis so should only be used if intravenous lorazepam is not immediately available. Absorption of diazepam from intramuscular injection or from suppositories is too slow for treatment of status epilepticus. When facilities for resuscitation are not immediately available or if unable to secure immediate intravenous access, diazepam can be administered as a rectal solution or midazolam oromucosal solution can be given into the buccal cavity.

Penicillins and the other ß-lactam antibiotics are bactericidal. They produce their antimicrobial action by preventing cross-linkage between the linear peptidoglycan polymer chains that make up the bacterial cell wall. They, therefore, inhibit cell wall synthesis.
An overview of the different mechanisms of action of the various types of antimicrobial agents is shown below:
Mechanism of action
Examples
Inhibition of cell wall synthesis
Penicillins
Cephalosporins
Vancomycin
Disruption of cell membrane function
Polymyxins
Nystatin
Amphotericin B
Inhibition of protein synthesis
Macrolides
Aminoglycosides
Tetracyclines
Chloramphenicol
Inhibition of nucleic acid synthesis
Quinolones
Trimethoprim
5-nitroimidazoles
Rifampicin
Anti-metabolic activity
Sulfonamides
Isoniazid

Because the middles of the shafts of the ribs are lower than either the anterior or posterior end, elevation of the ribs also moves the middles of the shafts laterally. This ‘bucket handle’ upwards and lateral movement increases the lateral dimensions of the thorax.

It’s crucial that thrombin’s impact is restricted to the injured site. Tissue factor pathway inhibitor (TFPI), which is produced by endothelial cells and found in plasma and platelets, is the first inhibitor to function. It accumulates near the site of harm induced by local platelet activation. Xa and VIIa, as well as tissue factor, are inhibited by TFPI. Other circulating inhibitors, the most potent of which is antithrombin, can also inactivate thrombin and other protease factors directly. Coagulation cofactors V and VIII are inhibited by protein C and protein S. Tissue plasminogen activator (TPA) from endothelial cells facilitates fibrinolysis by promoting the conversion of plasminogen to plasmin.

Overuse of cortisol medication, as seen in the treatment of patients with chronic asthma or rheumatoid arthritis, can cause Cushing’s syndrome.

Weight gain, thin arms and legs, a round face, increased fat around the base of the neck, a fatty hump between the shoulders, easy bruising, wide purple stretch marks primarily on the abdomen, breasts, hips, and under the arms, weak muscles, hirsutism, hypertension, erectile dysfunction, osteoporosis, frontal alopecia, acne, depression, poor wound healing, and polycythaemia are all clinical features of Cushing’s syndrome.

Anti-D is an IgG antibody that targets the antigen Rhesus D (RhD). Plasma from rhesus-negative donors who have been immunised against the anti-D-antigen is used to make anti-D immunoglobulin.

Only RhD negative women are given Anti-D Ig. Women who are RhD negative do not have the RhD antigen on their RBC. If a foetus has the RhD antigen (i.e. is RhD positive) and the mother is exposed to foetal blood, she may develop antibodies to RhD that pass through the placenta and attack foetal red cells (resulting in newborn haemolytic disease). Anti-D is given to bind and neutralise foetal red cells in the maternal circulation before an immune response is triggered. In the event of a sensitising event, 500 IU Anti-D Ig should be administered intramuscularly.

The following are examples of potentially sensitising events:
Birth
Haemorrhage during pregnancy
Miscarriage
Ectopic pregnancy
Death within the womb
Amniocentesis
Chorionic villus sampling
Trauma to the abdomen

The sooner anti-D is given in the event of a sensitising event, the better; however, it is most effective within 72 hours, and the BNF states that it is still likely to have some benefit if given outside of this time frame.

At 28 and 34 weeks, RhD negative women should receive routine antenatal prophylaxis. This is regardless of whether they have previously received Anti-D for a sensitising event during the same pregnancy.

Prophylactic anti-D is not necessary before 12 weeks gestation, as confirmed by scan, in uncomplicated miscarriage (where the uterus is not instrumented), or mild, painless vaginal bleeding, as the risk of foeto-maternal haemorrhage (FMH) is negligible. In cases of therapeutic termination of pregnancy, whether by surgical or medical means, 250 IU of prophylactic anti-D immunoglobulin should be given to confirmed RhD negative women who are not known to be RhD sensitised.

Hutchinson sign relates to involvement of the tip of the nose from facial herpes zoster. It implies involvement of the external nasal branch of the nasociliary nerve which is a branch of the ophthalmic division of the trigeminal nerve.

The nasociliary branch of the trigeminal nerve innervates the apex and lateral aspect of the nose, as well as the cornea. Therefore, lesions on the side or tip of the nose should raise suspicion of ocular involvement.

Hospital-acquired pneumonia (HAP), or nosocomial pneumonia, is a lower respiratory infection that was not incubating at the time of hospital admission and that presents clinically 2 or more days after hospitalization. Pneumonia that presents sooner should be regarded as community­ acquired pneumonia. VAP refers to nosocomial pneumonia that develops among patients on ventilators. Ventilator-associated pneumonia (VAP) is defined as pneumonia that presents more than 48 hours after endotracheal intubation.

Common bacteria involved in hospital-acquired pneumonia (HAP) include the following [10] :
Pseudomonas Aeruginosa
Staphylococcus aureus, including methicillin-susceptible S aureus (MSSA) and methicillin-resistant S aureus (MRSA)
Klebsiella pneumoniae
Escherichia coli

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.

Examples of type I reactions include:
Allergic rhinitis
Allergic conjunctivitis
Allergic asthma
Systemic anaphylaxis
Angioedema
Urticaria
Penicillin allergy

Chickenpox infection in neonates, adults/adolescents and pregnant women is associated with more severe disease. Varicella zoster pneumonitis typically occurs in pregnant women or immunocompromised individuals and is associated with a high mortality. A live attenuated-virus vaccine is available and recommended for non-immune healthcare workers but is not part of the routine childhood immunisation schedule. Antiviral treatment is not typically recommended in childhood chickenpox but is indicated for shingles.

Antidiuretic hormone is synthesised in the hypothalamus and transported to the posterior pituitary within nerve fibres where it is stored in secretory granules. ADH binds V2 receptors on renal principal cells in the late distal tubule and collecting ducts, raising cAMP levels and causing intracellular vesicles to fuse with the apical membrane. In their membrane these vesicles have water channels called aquaporins, which increase the water permeability allowing greater water reabsorption and concentration of urine. Excess levels of ADH results in syndrome of inappropriate ADH secretion (SIADH) characterised by hyponatremia with concomitant hypo-osmolality and high urine osmolality.

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

Flucloxacillin and gentamicin are current recommended by NICE and the BNF for the initial ‘blind’ therapy in endocarditis.

Diabetes insipidus is the inability to produce concentrated urine. It is characterised by the presence of excessive thirst, polyuria and polydipsia. There are two distinct types of diabetes insipidus:
Cranial (central) diabetes insipidus and;
Nephrogenic diabetes insipidus
Cranial diabetes insipidus is caused by a deficiency of vasopressin (anti-diuretic hormone). Patients with cranial diabetes insipidus can have a urine output as high as 10-15 litres per 24 hours, but adequate fluid intake allows most patients to maintain normonatraemia. 30% of cases are idiopathic, and a further 30% are secondary to head injuries. Other causes include neurosurgery, brain tumours, meningitis, granulomatous disease (e.g. sarcoidosis) and drugs, such as naloxone and phenytoin. A very rare inherited form also exists that is associated with diabetes mellitus, optic atrophy, nerve deafness and bladder atonia.
Nephrogenic diabetes insipidus is caused by renal resistance to the action of vasopressin. As with cranial diabetes insipidus, urine output is markedly elevated. Serum sodium levels can be maintained by secondary polydipsia or can be elevated. Causes of nephrogenic diabetes insipidus include chronic renal disease, metabolic disorders (e.g. hypercalcaemia and hypokalaemia) and drugs, including long-term lithium usage and demeclocycline.
In view of the history of long-term lithium use, in this case, nephrogenic diabetes insipidus is the most likely diagnosis.

Multiple myeloma is a clonal abnormality affecting plasma cells in which there is an overproduction of functionless immunoglobulins. The most common patient complaint is bone pain, especially in the back and ribs. Anaemia and renal failure are common, along with hypercalcemia. Hypercalcemia may lead to an altered mental status, as in this case.

Chronic lymphocytic leukaemia occurs due to the overproduction of lymphocytes, usually B cells. CLL may present with an asymptomatic elevation of B cells. Patients are generally more than 50 years old and present with non-specific fatigue and weight loss symptoms.

There is no history of alcohol abuse in this case. Furthermore, patients with a history of alcohol abuse may have signs of liver failure, which are not present here.

Metastatic prostate cancer would most often cause lower backache as it metastasises first to the lumbar spine via the vertebral venous plexus.

A patient with Vitamin B12 deficiency would have anaemia, megaloblastic, hypersegmented neutrophils, and signs of peripheral neuropathy.

Caput medusae is a condition that consists of collateral veins radiating from the umbilicus and results from recanalization of the umbilical vein.

Under normal conditions, the portal venous blood traverses the liver and drains into the inferior vena cava of the systemic venous circulation by way of the hepatic veins. This is the direct route. However, other, smaller communications exist between the portal and systemic systems, and they become important when the direct route becomes blocked. These communications are as follows:

At the lower third of the oesophagus, the oesophageal branches of the left gastric vein (portal tributary) anastomose with the oesophageal veins draining the middle third of the oesophagus into the azygos veins (systemic tributary).

Halfway down the anal canal, the superior rectal veins (portal tributary) draining the upper half of the anal canal anastomosis with the middle and inferior rectal veins (systemic tributaries), which are tributaries of the internal iliac and internal pudendal veins, respectively.

The paraumbilical veins connect the left branch of the portal vein with the superficial veins of the anterior abdominal wall (systemic tributaries). The paraumbilical veins travel in the falciform ligament and accompany the ligamentum teres.

The veins of the ascending colon, descending colon, duodenum, pancreas, and liver (portal tributary) anastomose with the renal, lumbar, and phrenic veins (systemic tributaries).

Hyperacute bacterial conjunctivitis is a severe, sight-threatening ocular infection that warrants immediate ophthalmic work-up and management. The infection has an abrupt onset and is characterized by a copious yellow-green purulent discharge that reaccumulates after being wiped away. Typically caused by infection with Neisseria gonorrhoeae.

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

Persons with chronic diseases. Persons with chronic renal disease or undergoing dialysis, and those with hyposplenism or asplenia, may receive BCG vaccine if indicated.

Only 2 absolute contraindications apply to all vaccines:

• anaphylaxis following a previous dose of the relevant vaccine
• anaphylaxis following any component of the relevant vaccine

2 further contraindications apply to live vaccines (both parenteral and oral):

• People who are significantly immunocompromised should not receive live vaccines. This is regardless of whether the immunocompromising condition is caused by disease or treatment.
• Pregnant women should not receive live vaccines, in general. Women should be advised not to become pregnant within 28 days of receiving a live vaccine.

Use of live vaccines in people who are immunocompromised:
People who are immunocomprised are at risk of adverse events or vaccine-related disease if they receive a live vaccine.

Live vaccines include:

BCG (bacille Calmette–Guérin) vaccine
oral cholera vaccine (Vaxchora)
Some Japanese encephalitis virus vaccines
MMR (measles-mumps-rubella) vaccine
rotavirus vaccine
oral typhoid vaccine
varicella vaccine
yellow fever vaccine
zoster vaccine (Zostavax)

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.

Carbonic anhydrase inhibitors e.g. acetazolamide block the reaction of carbon dioxide and water and so prevent Na+/H+exchange and bicarbonate reabsorption. The increased bicarbonate levels in the filtrate oppose water reabsorption. Proximal tubule sodium reabsorption is also reduced because it is partly dependent on bicarbonate reabsorption.

Syncope and sudden death due to ventricular tachycardia, particularly Torsades-des-pointes is seen in prolongation of the QT interval.

The causes of a prolonged QT interval include:
Erythromycin
Amiodarone
Quinidine
Methadone
Procainamide
Sotalol
Terfenadine
Tricyclic antidepressants
Jervell-Lange-Nielsen syndrome (autosomal dominant)
Romano Ward syndrome (autosomal recessive)
Hypothyroidism
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Hypothermia
Rheumatic carditis
Mitral valve prolapse
Ischaemic heart disease

CSF is separated from the blood by the blood-brain barrier. This barrier is impermeable to polar molecules such as H+and HCO3-but CO2can diffuse across it easily. The pH of CSF is therefore determined by the arterial PCO2and the CSF HCO3-and is not affected by blood pH.

C1 – C4 INJURY
Most severe of the spinal cord injury levels; paralysis in arms, hands, trunk and legs; patient may not be able to breathe on his or her own, cough, or control bowel or bladder movements; ability to speak is sometimes impaired or reduced

C5 INJURY
Person can raise his or her arms and bend elbows; likely to have some or total paralysis of wrists, hands, trunk and legs; can speak and use diaphragm, but breathing will be weakened

C6 INJURY
Nerves affect wrist extension; paralysis in hands, trunk and legs, typically; should be able to bend wrists back; can speak and use diaphragm, but breathing will be weakened

C7 INJURY
Nerves control elbow extension and some finger extension; most can straighten their arm and have normal movement of their shoulders

C8 INJURY
Nerves control some hand movement; should be able to grasp and release objects

C5 – Elbow flexors (biceps, brachialis)
C6 – Wrist extensors (extensor carpi radialis longus and brevis)
C7 – Elbow extensors (triceps)
C8 – Finger flexors (flexor digitorum profundus) to the middle finger

C5 – Elbow flexed at 90 degrees, arm at the patient’s side and forearm supinated
C6 – Wrist in full extension
C7 – Shoulder is neutral rotation, adducted and in 90 degrees of flexion with elbow in 45 degrees of flexion
C8 –Full flexed position of the distal phalanx with the proximal finger joints stabilized in a extended position

Anaphylaxis can be triggered by any of a very broad range of triggers, but those most commonly identified include food, drugs, latex and venom. Of foods, nuts are the most common cause; muscle relaxants, antibiotics, NSAIDs and aspirin are the most commonly implicated drugs. Food is the commonest trigger in children and drugs the commonest in adults. A significant number of cases are idiopathic. Most reactions occur over several minutes; rarely, reactions may be slower in onset. The speed of onset of the reaction depends on the trigger e.g. intravenous medications will cause a more rapid onset than stings which in turn will cause a more rapid onset than ingestion of food.